https://www.explorationpub.com/Journals/em Most Recent Articles : Exploration of Medicine. en-us Tue, 29 Apr 2025 10:20:56 GMT https://www.explorationpub.com/Journals/em/Article/10012 Retinopathy of prematurity (ROP) is a blinding morbidity of preterm infants, which represents a significant clinical problem, accounting for up to 40% of all childhood blindness. ROP displays a range of severity, though even mild disease may result in life-long visual impairment. This is complicated by the fact that our current treatments have significant ocular and potentially systemic effects. Therefore, disease prevention is desperately needed to mitigate the life-long deleterious effects of ROP for preterm infants. Although ROP demonstrates a delayed onset of retinal disease following preterm birth, representing a potential window for prevention, we have been unable to sufficiently alter the natural disease course and meaningfully prevent ROP. Prevention therapeutics requires knowledge of early ROP molecular changes and risk, occurring prior to clinical retinal disease. While we still have an incomplete understanding of these disease mechanisms, emerging data integrating contributions of maternal/placental pathobiology with ROP are poised to inform novel approaches to prevention. Herein, we review the molecular basis for current prevention strategies and the clinical outcomes of these interventions. We also discuss how insights into early ROP pathophysiology may be gained by a better understanding of maternal and placental factors playing a role in preterm birth. Review Sat, 29 Feb 2020 00:00:00 GMT LaraCarroll, Leah A.Owen, Sat, 29 Feb 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/10012 https://www.explorationpub.com/Journals/em/Article/10013 Aim: Racial disparities in opioid use disorder (OUD) management exist, however, and there is limited research on factors that influence opioid cessation in different population groups. Methods: We employed multiple machine learning prediction algorithms least absolute shrinkage and selection operator, random forest, deep neural network, and support vector machine to assess factors associated with ceasing opioid use in a sample of 1,192 African Americans (AAs) and 2,557 individuals of European ancestry (EAs) who met Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria for OUD. Values for nearly 4,000 variables reflecting demographics, alcohol and other drug use, general health, non-drug use behaviors, and diagnoses for other psychiatric disorders, were obtained for each participant from the Semi-Structured Assessment for Drug Dependence and Alcoholism, a detailed semi-structured interview. Results: Support vector machine models performed marginally better on average than other machine learning methods with maximum prediction accuracies of 75.4% in AAs and 79.4% in EAs. Subsequent stepwise regression considered the 83 most highly ranked variables across all methods and models and identified less recent cocaine use (AAs: odds ratio (OR) = 1.82, P = 9.19 × 10−5; EAs: OR = 1.91, P = 3.30 × 10−15), shorter duration of opioid use (AAs: OR = 0.55, P = 5.78 × 10−6; EAs: OR = 0.69, P = 3.01 × 10−7), and older age (AAs: OR = 2.44, P = 1.41 × 10−12; EAs: OR = 2.00, P = 5.74 × 10−9) as the strongest independent predictors of opioid cessation in both AAs and EAs. Attending self-help groups for OUD was also an independent predictor (P < 0.05) in both population groups, while less gambling severity (OR = 0.80, P = 3.32 × 10−2) was specific to AAs and post-traumatic stress disorder recovery (OR = 1.93, P = 7.88 × 10−5), recent antisocial behaviors (OR = 0.64, P = 2.69 × 10−3), and atheism (OR = 1.45, P = 1.34 × 10−2) were specific to EAs. Factors related to drug use comprised about half of the significant independent predictors in both AAs and EAs, with other predictors related to non-drug use behaviors, psychiatric disorders, overall health, and demographics. Conclusions: These proof-of-concept findings provide avenues for hypothesis-driven analysis, and will lead to further research on strategies to improve OUD management in EAs and AAs. Original Article Sat, 29 Feb 2020 00:00:00 GMT Jiayi W.Cox, Richard M.Sherva, Kathryn L.Lunetta, RichardSaitz, MarkKon, Henry R.Kranzler, JoelGelernter, Lindsay A.Farrer, Sat, 29 Feb 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/10013 https://www.explorationpub.com/Journals/em/Article/10014 Chronic kidney disease (CKD) is a disease regularly seen in clinical practice. At present, CKD is described as a change of kidney structure and/or function and it is classified in relation to cause, values of glomerular filtration rate and albuminuria category. Seeing that CKD is closely linked to the development of end-stage renal disease and other comorbidities, the determination of additional independent predictors for CKD is clinically necessary. At present, there is evidence associating non-alcoholic fatty liver disease (NAFLD) with CKD, thereby suggesting that NAFLD patients may require intensive surveillance to reduce their risk of CKD. In 2008, genome-wide association studies documented an association between the variant rs738409 (C > G p.I148M) in the patatin-like phospholipase domain containing 3 (PNPLA3) gene (mainly implicated in the lipid regulation) and the entire spectrum of NAFLD (i.e., liver steatosis, non-alcoholic steatohepatitis, fibrosis, and hepatocellular carcinoma). In the last years, accumulating epidemiological evidence suggests the existence of a relationship between PNPLA3 rs738409 and risk of CKD, indicating that rs738409 may also contribute to the kidney injury. This is of particular scientific interest, as such association may explain, at least in part, the epidemiological association between liver and kidney disease. In this narrative review, we will discuss the accumulating evidence regarding the association between PNPLA3 rs738409 and risk of CKD, the putative biological mechanisms underpinning such relationship, and the possible future perspective. Review Sat, 29 Feb 2020 00:00:00 GMT AlessandroMantovani, ChiaraZusi, Sat, 29 Feb 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/10014 https://www.explorationpub.com/Journals/em/Article/10011 Not applicable. Editorial Sat, 29 Feb 2020 00:00:00 GMT Lindsay A.Farrer, Sat, 29 Feb 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/10011 https://www.explorationpub.com/Journals/em/Article/10015 Non-alcoholic fatty liver disease (NAFLD) remains a major cause of chronic liver disease worldwide. Despite extensive studies, the heterogeneity of the risk factors as well as different disease mechanisms complicate the goals toward effective diagnosis and management. Recently, it has been shown that sex differences play a role in the prevalence and progression of NAFLD. In vitro, in vivo, and clinical studies revealed that the lower prevalence of NAFLD in premenopausal as compared to postmenopausal women and men is mainly due to the protective effects of estrogen and body fat distribution. It has been also described that males and females present differential pathogenic features in terms of biochemical profiles and histological characteristics. However, the exact molecular mechanisms for the gender differences that exist in the pathogenesis of NAFLD are still elusive. Lipogenesis, oxidative stress, and inflammation play a key role in the progression of NAFLD. For NAFLD, only a few studies characterized these mechanisms at the molecular level. Therefore, we aim to review the reported differential molecular mechanisms that trigger such different pathogenesis in both sexes. Differences in lipid metabolism, glucose homeostasis, oxidative stress, inflammation, and fibrosis were discussed based on the evidence reported in recent publications. In conclusion, with this review, we hope to provide a new perspective for the development of future practice guidelines as well as a new avenue for the management of the disease. Review Thu, 30 Apr 2020 00:00:00 GMT Noel C.Salvoza, Pablo J.Giraudi, ClaudioTiribelli, NataliaRosso, Thu, 30 Apr 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/10015 https://www.explorationpub.com/Journals/em/Article/10016 Left ventricular ejection fraction is the critical parameter used for heart failure classification, decision making and assessing prognosis. It is defined as a volumetric ratio and is essentially a composite of arterial and ventricular elastances, but not intrinsic contractility. The clinician should be aware of its numerous limitations when measuring and reporting it. And make a step toward more insightful understanding of hemodynamics. Review Thu, 30 Apr 2020 00:00:00 GMT Elena-LauraAntohi, OvidiuChioncel, Thu, 30 Apr 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/10016 https://www.explorationpub.com/Journals/em/Article/10017 Rational government of patient fluxes from primary care to hepatology clinic is a priority of nonalcoholic fatty liver disease (NAFLD) research. Estimating pre-test probability of disease, risk of fibrosis progression, and exclusion of competing causes of liver disease must be addressed. Here we propose a novel taxonomic classification of NAFLD based on hepatic, pathogenic and systemic features of disease in the individual patient. The variable course of disease in any given patient remains a clinical enigma. Therefore, future studies will have to better characterize the role of genetic polymorphisms, family and personal history, diet, alcohol, physical activity and drugs as modifiers of the course of disease and clues to the early diagnosis of hepatocellular carcinoma. A better understanding of these, together with a taxonomic diagnosis, may prompt a more accurate personalization of care. For example, understanding the putative role of psycho-depression in NAFLD promises to revolutionize disease management in a proportion of cases. Similarly, sex differences in outcome and response to treatment are insufficiently characterized. More studies are awaited regarding those forms of NAFLD which occur secondary to endocrine derangements. The intersections between NAFLD and the lung must better be defined. These include the bi-directional associations of NAFLD and chronic obstructive pulmonary disease and sleep apnoea syndrome, as well as the totally unexplored chapter of NAFLD and coronavirus disease 2019 (COVID-19). Finally, the therapeutic roles of intermittent fasting and anticoagulation must be assessed. In conclusion, over the last 20 years, NAFLD has taught us a lot regarding the pathogenic importance of insulin resistance, the limitations of correcting this in the treatment of NAFLD, the root causes of diabetes and the metabolic syndrome, sex differences in disease and the role of nuclear receptors. However, the overwhelming COVID-19 pandemic is now expected to reset the priorities of public health. Review Mon, 29 Jun 2020 00:00:00 GMT AmedeoLonardo, StefanoBallestri, Mon, 29 Jun 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/10017 https://www.explorationpub.com/Journals/em/Article/100110 Aim: To test if the impairment of mononuclear cell (MNC) migration in patients with hereditary hemorrhagic telangiectasia (HHT) is due to the reduction of the endoglin (ENG) receptor on the cell surface and oxidative stress. Methods: MNCs of HHT patients and normal controls were subjected to migration assay. Fractions of MNCs were pre-incubated with antibodies specific to HHT causative genes ENG [hereditary hemorrhagic telangiectasia type 1 (HHT1)] or activin receptor-like kinase 1 [ALK1, hereditary hemorrhagic telangiectasia type 2 (HHT2)], AMD3100 or Diprotin-A to block ENG, ALK1 C-X-C chemokine receptor 4 (CXCR4) or CD26 (increased in HHT1 MNCs) before migration assay. The MNCs were allowed to migrate toward stromal cell-derived factor-1α (SDF-1α) for 18 h. The expression of CXCR4, CD26, superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPX1) in MNCs and nitric oxide levels in the plasma were analyzed. Results: Compared to the controls, fewer HHT1 MNCs and similar number of HHT2 MNCs migrated toward SDF-1α. Diprotin-A pre-treatment improved HHT1 MNC-migration, but had no effect on normal and HHT2 MNCs. Pre-incubation with an anti-ENG antibody reduced the migration of normal MNCs. Diprotin-A did not improve the migration of ENG antibody pre-treated MNCs. Anti-ALK1 antibody had no effect on MNC-migration. AMD3100 treatment reduced normal and HHT MNC-migration. ENG mRNA level was reduced in HHT1 and HHT2 MNCs. ALK1 mRNA was reduced in HHT2 MNCs only. CD26 expression was higher in HHT1 MNCs. Pre-treatment of MNCs with anti-ENG or anti-ALK1 antibody had no effect on CD26 and CXCR4 expression. The expression of antioxidant enzymes, SOD1, was reduced in HHT1 MNCs, which was accompanied with an increase of ROS in HHT MNCs and nitric oxide in HHT1 plasma. Conclusions: Reduction of ENG receptor on MNC surface reduced monocyte migration toward SDF-1α independent of CD26 expression. Increased oxidative stress could alter HHT MNC migration behavior. Original Article Mon, 29 Jun 2020 00:00:00 GMT ZhenyingHan, SonaliShaligram, Marie E.Faughnan, DewiClark, ZhengdaSun, HuaSu, Mon, 29 Jun 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100110 https://www.explorationpub.com/Journals/em/Article/10019 Aim: Epigenetic variation of DNA methylation of the mu-opioid receptor gene (OPRM1) has been identified in the blood and saliva of individuals with opioid use disorder (OUD) and infants with neonatal opioid withdrawal syndrome (NOWS). It is unknown whether epigenetic variation in OPRM1 exists within placental tissue in women with OUD and whether it is associated with NOWS outcomes. In this pilot study, the authors aimed to 1) examine the association between placental OPRM1 DNA methylation levels and NOWS outcomes, and 2) compare OPRM1 methylation levels in opioid-exposed versus non-exposed control placentas. Methods: Placental tissue was collected from eligible opioid (n = 64) and control (n = 29) women after delivery. Placental DNA was isolated and methylation levels at six cytosine-phosphate-guanine (CpG) sites within the OPRM1 promoter were quantified. Methylation levels were evaluated for associations with infant NOWS outcome measures: need for pharmacologic treatment, length of hospital stay (LOS), morphine treatment days, and treatment with two medications. Regression models were created and adjusted for clinical co-variates. Methylation levels between opioid and controls placentas were also compared. Results: The primary opioid exposures were methadone and buprenorphine. Forty-nine (76.6%) of the opioid-exposed infants required pharmacologic treatment, 10 (15.6%) two medications, and average LOS for all opioid-exposed infants was 16.5 (standard deviation 9.7) days. There were no significant associations between OPRM1 DNA methylation levels in the six CpG sites and any NOWS outcome measures. No significant differences were found in methylation levels between the opioid and control samples. Conclusions: No significant associations were found between OPRM1 placental DNA methylation levels and NOWS severity in this pilot cohort. In addition, no significant differences were seen in OPRM1 methylation in opioid versus control placentas. Future association studies examining methylation levels on a genome-wide level are warranted. Original Article Mon, 29 Jun 2020 00:00:00 GMT Elisha M.Wachman, AliceWang, Breanna C.Isley, JefferyBoateng, Jacob A.Beierle, AaronHansbury, HiraShrestha, CamronBryant, HuipingZhang, Mon, 29 Jun 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/10019 https://www.explorationpub.com/Journals/em/Article/10018 Aim: Recent randomized controlled trials (RCTs) have tested the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RA) to specifically treat non-alcoholic fatty liver disease (NAFLD). We performed a meta-analysis of RCTs to investigate the efficacy of GLP-1 RAs for treatment of NAFLD or non-alcoholic steatohepatitis (NASH). Methods: We systematically searched PubMed and ClinicalTrials.Gov databases utilizing specific terms to identify placebo-controlled or head-to-head RCTs (last research on March 1, 2020) involving NAFLD patients with the aim of evaluating the efficacy of GLP-1 RAs to treat NAFLD/NASH. Primary outcomes were changes in serum liver enzymes, liver fat content, or histologic resolution of NASH. Weighted mean differences (WMD) were used to test the differences between the treatment arms. Results: Overall, we found 7 placebo-controlled or head-to-head RCTs involving 472 middle-aged individuals (66% men; 77% with established diabetes) followed for a median of 16 weeks that have used liraglutide or exenatide to treat NAFLD on imaging (n = 6) or biopsy (n = 1). Compared to placebo or reference therapy, treatment with GLP-1 RAs decreased serum alanine aminotransferase [n = 7 studies; WMD: –8.77 IU/L, 95% confidence intervals (CI) –17.69 to 0.14 IU/L; I2 = 87.3%], gamma-glutamyltransferase levels (n = 4 studies; WMD: –10.17 IU/L, 95% CI –14.27 IU/L to –6.07 IU/L; I2 = 0%) and imaging-defined liver fat content (n = 4 studies; WMD: –6.23%, 95% CI –8.95% to –3.51%; I2 = 85.9%). In one RCT involving 55 patients with biopsy-proven NASH, a 48-week treatment with liraglutide also led to a greater histological resolution of NASH than placebo. Conclusions: GLP-1 RAs (mostly liraglutide) seem to be a promising treatment option for NAFLD or NASH. Meta-Analysis Mon, 29 Jun 2020 00:00:00 GMT AlessandroMantovani, GiorgiaBeatrice, GrazianaPetracca, FilippoPampagnin, DamianoSandri, GiovanniTargher, Mon, 29 Jun 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/10018 https://www.explorationpub.com/Journals/em/Article/100111 Nonalcoholic fatty liver disease (NAFLD) is a substantial and growing problem worldwide and has become the second most common indication for liver transplantation as it may progress to cirrhosis and develop complications from portal hypertension primarily caused by advanced fibrosis and erratic tissue remodeling. However, elevated portal venous pressure has also been detected in experimental models of fatty liver and in human NAFLD when fibrosis is far less advanced and cirrhosis is absent. Early increases in intrahepatic vascular resistance may contribute to the progression of liver disease. Specific pathophenotypes linked to the development of portal hypertension in NAFLD include hepatocellular lipid accumulation and ballooning injury, capillarization of liver sinusoidal endothelial cells, enhanced contractility of hepatic stellate cells, activation of Kupffer cells and pro-inflammatory pathways, adhesion and entrapment of recruited leukocytes, microthrombosis, angiogenesis and perisinusoidal fibrosis. These pathological events are amplified in NAFLD by concomitant visceral obesity, insulin resistance, type 2 diabetes and dysbiosis, promoting aberrant interactions with adipose tissue, skeletal muscle and gut microbiota. Measurement of the hepatic venous pressure gradient by retrograde insertion of a balloon-tipped central vein catheter is the current reference method for predicting outcomes of cirrhosis associated with clinically significant portal hypertension and guiding interventions. This invasive technique is rarely considered in the absence of cirrhosis where currently available clinical, imaging and laboratory correlates of portal hypertension may not reflect early changes in liver hemodynamics. Availability of less invasive but sufficiently sensitive methods for the assessment of portal venous pressure in NAFLD remains therefore an unmet need. Recent efforts to develop new biomarkers and endoscopy-based approaches such as endoscopic ultrasound-guided measurement of portal pressure gradient may help achieve this goal. In addition, cellular and molecular targets are being identified to guide emerging therapies in the prevention and management of portal hypertension. Review Mon, 29 Jun 2020 00:00:00 GMT MarvinRyou, NicholasStylopoulos, GyorgyBaffy, Mon, 29 Jun 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100111 https://www.explorationpub.com/Journals/em/Article/100112 Pooled prevalence of nonalcoholic fatty liver disease (NAFLD) globally is about 25%. Nonalcoholic steatohepatitis (NASH) with advanced fibrosis has been linked with substantial morbidity and mortality, without having to-date any licensed treatment. C-C chemokine receptor (CCR) antagonists have been investigated as candidates for the treatment of NASH. Inhibition of CCR2 is expected to mitigate hepatic inflammation, through reducing the activation of Kupffer cells, as well as the infiltration of monocytes and macrophages into the liver. Inhibition of CCR5 is expected to mitigate hepatic fibrogenesis, through impairing the activation of hepatic stellate cells, as well as to mitigate hepatic inflammation, through impairing the activation of Kupffer cells and macrophages. Cenicriviroc (CVC) is the first in class, dual inhibitor of CCR2 and CCR5. After exhibiting favorable results in animal models, CVC was shown to be beneficial in NASH patients with more severe fibrosis at a phase 2b trial (CENTAUR) and is currently at a phase 3 clinical trial (AURORA). Apart from CVC, other CCR5 mono-antagonists, such as maraviroc, are under evaluation in clinical trials with human immunodeficiency virus patients with NAFLD. The aim of this review was to summarize existing evidence on CVC and other CCR antagonists in NASH patients, primarily focusing on their clinical efficacy and safety. Review Fri, 03 Jul 2020 00:00:00 GMT MichaelDoulberis, KasianiPapadimitriou, ApostolisPapaefthymiou, JannisKountouras, Stergios A.Polyzos, Fri, 03 Jul 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100112 https://www.explorationpub.com/Journals/em/Article/100116 The currently ongoing coronavirus disease 19 (COVID-19) pandemic has affected globally human health and economy. Research in progress has shown facts associated with this disease and raised questions relevant for disease control and prevention. In this perspective, the collaboration between science and art in visual communication using the artwork “Enseñanza” (“Teaching”) contributes to the representation of the lessons learned from COVID-19 and the way forward. To advance preparedness for current and future pandemics, the authors propose to address international collaborations, support to science, access to food supplies and health services, sustainable development and a “One Health” approach searching a balanced interaction of humanity with nature and a more holistic approach to disease prevention and control. Perspective Fri, 17 Jul 2020 00:00:00 GMT Joséde la Fuente, JoséBedia, ChristianGortázar, Fri, 17 Jul 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100116 https://www.explorationpub.com/Journals/em/Article/100113 Diabetes and cancer are widespread worldwide and the number of subjects presenting both diseases increased over the years. The management of cancer patients having diabetes represents a challenge not only because of the complexity and heterogeneity of these pathologies but also for the lack of standardised clinical guidelines. The diagnosis of cancer is traumatizing and monopolizes the attention of both patients and caregivers. Thus, pre-existent or new-onset diabetes can be overshadowed thus increasing the risk for short- and long-term adverse events. Moreover, drugs used for each disease can interfere with the clinical course of the concomitant disease, making challenging the management of these patients. Over the years, this issue has become more relevant because of the increased patients’ life expectancy due to the improved efficacy of diabetes and cancer therapies. The purpose of this review is to highlight what is known and what should be taken into consideration to optimise the clinical management of patients with diabetes and cancer. Due to the complexity of these diseases, a multidisciplinary, shared approach, including all the protagonists involved, is necessary to improve patients’ quality of life and lifespan. Review Sat, 08 Aug 2020 00:00:00 GMT AgostinoMilluzzo, PaoloVigneri, FedericaMartorana, RiccardoVigneri, LauraSciacca, Sat, 08 Aug 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100113 https://www.explorationpub.com/Journals/em/Article/100115 The prevalence of nonalcoholic or more recently re-defined metabolic associated fatty liver disease (MAFLD) is rapidly growing worldwide. It is characterized by hepatic fat accumulation exceeding 5% of liver weight not attributable to alcohol consumption. MAFLD refers to an umbrella of conditions ranging from simple steatosis to nonalcoholic steatohepatitis which may finally progress to cirrhosis and hepatocellular carcinoma. MAFLD is closely related to components of the metabolic syndrome and to environmental factors. In addition to the latter, genetic predisposition plays a key role in MAFLD pathogenesis and strictly contributes to its progressive forms. The candidate genes which have been related to MAFLD hereditability are mainly involved in lipids remodeling, lipid droplets assembly, lipoprotein packaging and secretion, de novo lipogenesis, and mitochondrial redox status. In the recent years, it has emerged the opportunity to translate the genetics into clinics by aggregating the genetic variants mostly associated with MAFLD in polygenic risk scores. These scores might be used in combination with metabolic factors to identify those patients at higher risk to develop more severe liver disease and to schedule an individual therapeutic approach. Review Sat, 08 Aug 2020 00:00:00 GMT MaricaMeroni, MiriamLongo, PaolaDongiovanni, Sat, 08 Aug 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100115 https://www.explorationpub.com/Journals/em/Article/100114 Nonalcoholic fatty liver disease (NAFLD) is a serious condition that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD is associated with metabolic syndrome (MetS) and all of its components. According to data, around 25–30% of population has NAFLD. Giving the growing incidence of MetS, obesity and diabetes mellitus type 2, NAFLD related terminal-stage liver disease is becoming prevailing indication for liver transplantation. In order to prevent terminal stage of this disease, it is crucial to determine those that are in risk group, to modify their risk factors and monitor their potential progression. In the absence of other causes of chronic liver disease, the prime diagnosis of NAFLD in daily clinical practice includes anamnesis, laboratory results (increased levels of aminotransferases and gammaglutamil transferases) and imaging methods. The biggest challenge with NAFLD patients is to differentiate simple steatosis from nonalcoholic steatohepatitis, and detection of fibrosis, that is the main driver in NAFLD progression. The gold standard for NAFLD diagnosis still remains the liver biopsy (LB). However, in recent years many noninvasive methods were invented, such as transient elastography (TE). TE (FibroScan®, Echosens, Paris, France) is used for diagnosis of pathological differences of liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). Investigations in the last years have confirmed that elastographic parameters of steatsis (CAP) and fibrosis (LSM) are reliable biomarkers to non-invasively assess liver steatosis and fibrosis respectively in NAFLD patients. A quick, straightforward and non-invasive method for NAFLD screening in patients with MetS components is TE-CAP. Once diagnosed, the next step is to determine the presence of fibrosis by LSM which should point out high risk patients. Those patients should be referred to hepatologists. LB may be avoided in a substantial number of patients if TE with CAP is used for screening. Review Mon, 31 Aug 2020 00:00:00 GMT IvanaMikolasevic, AndelaLukic, ToniJuric, MiaKlapan, PetraMadzar, NikolaKrolo, DorisKolovrat, IvankaJurica, IvaKedmenec, DomagojKihas, DorisIlovaca, IvanErstic, VandaHaralovic, DanijelCavlina, EmaDejhalla, DanijelaErdeljac, BenjaminVukalovic, NadijaSkenderevic, SandraMilic, Mon, 31 Aug 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100114 https://www.explorationpub.com/Journals/em/Article/100117 Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver chronic disease worldwide. The pathogenesis of NAFLD is complex and involves many metabolic enzymes and multiple pathways. Posttranslational modifications of proteins (PMPs) added another layer of complexity to the pathogenesis of NAFLD. PMPs change protein properties and regulate many biological functions, including cellular localization, stability, intracellular signaling, and protein function. Lysine acetylation is a common reversible PMP that consists of the transfer of an acetyl group from acetyl-coenzyme A (CoA) to a lysine residue on targeted proteins. The deacetylation reaction is catalyzed by deacetylases called sirtuins. This review summarizes the role of acetylation in NAFLD with a focus on sirtuins 1 and 3. Review Mon, 31 Aug 2020 00:00:00 GMT FatihaNassir, Mon, 31 Aug 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100117 https://www.explorationpub.com/Journals/em/Article/100118 Non-alcoholic fatty liver disease (NAFLD) has become the most common liver alteration worldwide. It encompasses a spectrum of disorders that range from simple steatosis to a progressive form, defined non-alcoholic steatohepatitis (NASH), that can lead to advanced fibrosis and eventually cirrhosis and hepatocellular carcinoma. On liver histology, NASH is characterized by the concomitant presence of significant fat accumulation and inflammatory reaction with hepatocellular injury. Until now, liver biopsy is still required to differentiate simple steatosis from NASH and evaluate the degree of liver fibrosis. Unfortunately, this technique has well-known limitations, including invasiveness and expensiveness. Moreover, it may be biased by sampling error and intra- or inter-observed variability. Furthermore, due to the increasing prevalence of NAFLD worldwide, to program a systematic screening with liver biopsy is not imaginable. In recent years, different techniques were developed and validated with the aim of non-invasively identifying NASH and assess liver fibrosis degrees. The non-invasive tests range from simple blood-tests analyses to composite scores and complex imaging techniques. Nevertheless, even if they could represent cost-effective strategies for diagnosing NASH, advanced fibrosis and cirrhosis, their accuracy and consequent usefulness are to be discussed. With this aim, in this review the authors summarize the current state of non-invasive assessment of NAFLD. In particular, in addition to the well-established tests, the authors describe the future perspectives in this field, reporting the latest tests based on OMICS, gut-miocrobioma and micro-RNAs. Finally, the authors provide an accurate assessment of how these non-invasive tools perform in clinical practice depending on the clinical context, with the aim of giving the clinicians a useful tool to try to resolve the diagnostic conundrum of NAFLD. Review Fri, 25 Sep 2020 00:00:00 GMT ValerioRosato, MarioMasarone, AndreaAglitti, MarcelloPersico, Fri, 25 Sep 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100118 https://www.explorationpub.com/Journals/em/Article/100119 The pathophysiological mechanisms underlying the close relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are multiple, complex and only partially known. The purpose of this paper was to review the current knowledge of these mechanisms in a unified manner. Subjects with NAFLD and T2DM have established insulin resistance (IR), which exacerbates the two comorbidities. IR worsens NAFLD by increasing the accumulation of free fatty acids (FFAs) in the liver. This occurs due to an increase in the influx of FFAs from peripheral adipose tissue by the activation of hormone-sensitive lipase. In addition, there is de novo increased lipogenesis, a transcription factor, the sterols regulatory element-binding transcription factor 1c (SREBP-1c), which activates the expression of several genes strongly promotes lipogenesis by the liver and facilitate storage of triglycerides. Lipids accumulation in the liver induces a chronic stress in the endoplasmic reticulum of the hepatocytes. Genome-wide association studies have identified genetic variants associated with NAFLD severity, but unrelated to IR. In particular, the alteration of patatin-like phospholipase domain-containing protein 3 contributes to the susceptibility to NAFLD. Furthermore, the lipotoxicity of ceramides and diacylglycerol, well known in T2DM, triggers a chronic inflammatory process favoring the progression from hepatic steatosis to steatohepatitis. Reactive oxygen species produced by mitochondrial dysfunction trigger both liver inflammation and beta-cells damage, promoting the progression of both NAFLD and T2DM. The close association between NAFLD and T2DM is bidirectional, as T2DM may trigger both NAFLD onset and its progression, but NAFLD itself may contribute to the development of IR and T2DM. Future studies on the mechanisms will have to deepen the knowledge of the interaction between the two pathologies and should allow the identification of new therapeutic targets for the treatment of NAFLD, currently substantially absent. Review Fri, 11 Sep 2020 00:00:00 GMT CarloAcierno, AlfredoCaturano, Pia ClaraPafundi, RiccardoNevola, Luigi ElioAdinolfi, Ferdinando CarloSasso, Fri, 11 Sep 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100119 https://www.explorationpub.com/Journals/em/Article/100120 Not applicable. Commentary Fri, 09 Oct 2020 00:00:00 GMT AlessandroMantovani, ElisabettaRinaldi, ChiaraZusi, Fri, 09 Oct 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100120 https://www.explorationpub.com/Journals/em/Article/100121 Technology in diabetes is rapidly evolving, with the aim of helping affected people to safely optimize their blood glucose control. New technologies are now considered as an essential tool for managing glycemia predominantly in people with type 1 diabetes, and clinical trials have demonstrated that in these subjects the use of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems are associated with improved glycemic control along with a better quality of life. Literature regarding technologies and type 2 diabetes is relatively lacking, but innovations may have an important role also in the management of these patients. Some studies in adults with type 2 diabetes have shown benefits with the use of CGM in terms of glycemic variability and improved therapeutic adjustments. Clinical trials about CSII and CGM use in type 2 diabetes may have some pitfalls and future studies are needed to assess how these advanced systems could improve clinical outcomes and also ensure cost-effectiveness in this population. In this narrative review, we aim to highlight the most relevant studies on this topic and to focus on the potential role of new technological devices in type 2 diabetes management. Review Sat, 31 Oct 2020 00:00:00 GMT ErikaPedone, AndreaLaurenzi, AgneseAllora, Andrea MarioBolla, AmeliaCaretto, Sat, 31 Oct 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100121 https://www.explorationpub.com/Journals/em/Article/100123 Not applicable. Perspective Sat, 31 Oct 2020 00:00:00 GMT BhushanDharmadhikari, SreejitaPatra, PrabirPatra, Sat, 31 Oct 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100123 https://www.explorationpub.com/Journals/em/Article/100122 Aim: Quantitative analysis of brain single photon emission computed tomography (SPECT) perfusion imaging is dependent on normative datasets that are challenging to produce. This study investigated the combination of SPECT neuroimaging from a large clinical population rather than small numbers of controls. The authors hypothesized this “population template” would demonstrate noninferiority to a control dataset, providing a viable alternative for quantifying perfusion abnormalities in SPECT neuroimaging. Methods: A total of 2, 068 clinical SPECT scans were averaged to form the “population template”. Validation was three-fold. First, the template was imported into SPECT brain analysis software, MIMneuro®, and compared against its control dataset of 90 individuals through its region and cluster analysis tools. Second, a cohort of 100 cognitively impaired subjects was evaluated against both the population template and MIMneuro®’s normative dataset to compute region-based metrics. Concordance and intraclass correlation coefficients, mean square deviations, total deviation indices, and limits of agreement were derived from these data to measure agreement and test for noninferiority. Finally, the same patients were clinically read in CereMetrix® to confirm that expected perfusion patterns appeared after comparison to the template. Results: MIMneuro®’s default threshold for normality is ± 1.65 z-score and this served as our noninferiority margin. Direct comparison of the template to controls produced no regions that exceeded this threshold and all clusters identified were far from statistically significant. Agreement measures revealed consistency between the softwares and that CereMetrix® results were noninferior to MIMneuro®, albeit with proportional bias. Visual analysis also confirmed that expected perfusion patterns appeared when individual scans were compared to the population template within CereMetrix®. Conclusions: The authors demonstrated a population template was noninferior to a smaller control dataset despite inclusion of abnormal scans. This suggests that our patient-based population template can serve as an alternative for identifying and quantifying perfusion abnormalities in brain SPECT. Original Article Sat, 31 Oct 2020 00:00:00 GMT Lindsay M.Quandt, Cyrus A.Raji, Sat, 31 Oct 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100122 https://www.explorationpub.com/Journals/em/Article/100124 This commentary is the product of a concerted effort to understand the needs, barriers, and gaps in the field of speech and language biomarkers for Alzheimer’s disease (AD). It distills interviews, surveys, and extensive correspondence with global leaders in the areas of dementia research, clinical trials, linguistics, and data analytics into an idealized clinical-study design for the harmonized collection of voice recordings. The ultimate goal of the effort is to democratize the ongoing speech and language analytics efforts by making such rich datasets available to the wider research ecosystem. Commentary Tue, 24 Nov 2020 00:00:00 GMT Nicole L.Bjorklund, HowardFillit, KristinaMalzbender, ShobhaPurushothama, LamprosKourtis, Tue, 24 Nov 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100124 https://www.explorationpub.com/Journals/em/Article/100126 Aim: Research suggests that Alzheimer’s disease (AD) is heterogeneous with numerous subtypes. Through a proprietary interactive ML system, several underlying biological mechanisms associated with AD pathology were uncovered. This paper is an introduction to emerging analytic efforts that can more precisely elucidate the heterogeneity of AD. Methods: A public AD data set (GSE84422) consisting of transcriptomic data of postmortem brain samples from healthy controls (n = 121) and AD (n = 380) subjects was analyzed. Data were processed by an artificial intelligence platform designed to discover potential drug repurposing candidates, followed by an interactive augmented intelligence program. Results: Using perspective analytics, six perspective classes were identified: Class I is defined by TUBB1, ASB4, and PDE5A; Class II by NRG2 and ZNF3; Class III by IGF1, ASB4, and GTSE1; Class IV is defined by cDNA FLJ39269, ITGA1, and CPM; Class V is defined by PDE5A, PSEN1, and NDUFS8; and Class VI is defined by DCAF17, cDNA FLJ75819, and SLC33A1. It is hypothesized that these classes represent biological mechanisms that may act alone or in any combination to manifest an Alzheimer’s pathology. Conclusions: Using a limited transcriptomic public database, six different classes that drive AD were uncovered, supporting the premise that AD is a heterogeneously complex disorder. The perspective classes highlighted genetic pathways associated with vasculogenesis, cellular signaling and differentiation, metabolic function, mitochondrial function, nitric oxide, and metal ion metabolism. The interplay among these genetic factors reveals a more profound underlying complexity of AD that may be responsible for the confluence of several biological factors. These results are not exhaustive; instead, they demonstrate that even within a relatively small study sample, next-generation machine intelligence can uncover multiple genetically driven subtypes. The models and the underlying hypotheses generated using novel analytic methods may translate into potential treatment pathways. Original Article Thu, 10 Dec 2020 00:00:00 GMT BessiQorri, MikeTsay, AbhishekAgrawal, RhodaAu, JosephGeraci, Thu, 10 Dec 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100126 https://www.explorationpub.com/Journals/em/Article/100125 Glycemic homeostasis is an essential mechanism for the proper working of an organism. However, balance in blood lipid and protein levels also plays an important role. The discovery of the hormone insulin and the description of its function for glycemic control made fundamental scientific progress in this field. However, since then our view of the problem has been deeply influenced only in terms of glucose and insulin (in an insulin-centric and glucose-centric way). Based on recent scientific discoveries, a fine and sophisticated network of hormonal and metabolic interactions, involving almost every apparatus and tissue of the human body, has been theorized. Efficient metabolic homeostasis is founded on these intricate interactions. Although it is still not fully defined, this complex network can undergo alterations that lead to metabolic disorders such as diabetes mellitus (DM). The endocrine pancreas plays a crucial role in the metabolic balance of an organism, but insulin is just one of the elements involved and each single pancreatic islet hormone is worthy of our concern. Moreover, pancreatic hormones need to be considered in a general view, concerning both their systemic function as direct mediators and as hormones, which, in turn, are regulated by other hormones or other substances. This more complex scenario should be taken into account for a better understanding of the pathophysiology and the therapeutic algorithms of DM. As a consequence, improvements in modern medicine could help to contemplate this new perspective. This review is focused on some aspects of gut-pancreas interaction, aiming to integrate this synergy into a wider context involving other organs and tissues. Review Thu, 10 Dec 2020 00:00:00 GMT RobertaMalaguarnera, AlessandraScamporrino, AgneseFilippello, StefaniaDi Mauro, AlessandroMinardo, FrancescoPurrello, SalvatorePiro, Thu, 10 Dec 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100125 https://www.explorationpub.com/Journals/em/Article/100127 Aim: Despite its high frequency of occurrence, mild traumatic brain injury (mTBI), or concussion, is difficult to recognize and diagnose, particularly in pediatric populations. Conventional methods to diagnose mTBI primarily rely on clinical questionnaires and sometimes include neuroimaging or pencil and paper neuropsychological testing. However, these methods are time consuming, require administration/interpretation from health professionals, and lack adequate test sensitivity and specificity. This study explores the use of BrainCheck Sport, a computerized neurocognitive test that is available on iPad, iPhone, or computer desktop, for mTBI assessment. The BrainCheck Sport Battery consists of 6 gamified traditional neurocognitive tests that assess areas of cognition vulnerable to mTBI such as attention, processing speed, executing functioning, and coordination. Methods: We administered BrainCheck Sport to 10 participants diagnosed with mTBI at the emergency department of Children’s hospital or local high school within 96 h of injury, and 115 normal controls at a local high school. Statistical analysis included Mann-Whitney U test, chi-square tests, and Hochberg tests to examine differences between the mTBI group and control group on each assessment in the battery. Significant metrics from these assessments were used to build a logistic regression model that distinguishes mTBI from control participants. Results: BrainCheck Sport was able to detect significant differences in Coordination, Stroop, Immediate/Delayed Recognition between normal controls and mTBI patients. Receiver operating characteristic (ROC) analysis of our logistic regression model found a sensitivity of 84% and specificity of 81%, with an area under the curve of 0.884. Conclusions: BrainCheck Sport has potential in distinguishing mTBI from control participants, by providing a shorter, gamified test battery to assess cognitive function after brain injury, while also providing a method for tracking recovery with the opportunity to do so remotely from a patient’s home. Original Article Thu, 31 Dec 2020 00:00:00 GMT SiaoYe, BrianKo, Huy Q.Phi, KevinSun, David M.Eagleman, BenjaminFlores, YaelKatz, BinHuang, Reza HosseiniGhomi, Thu, 31 Dec 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100127 https://www.explorationpub.com/Journals/em/Article/100128 Aim: Human voice contains rich information. Few longitudinal studies have been conducted to investigate the potential of voice to monitor cognitive health. The objective of this study is to identify voice biomarkers that are predictive of future dementia. Methods: Participants were recruited from the Framingham Heart Study. The vocal responses to neuropsychological tests were recorded, which were then diarized to identify participant voice segments. Acoustic features were extracted with the OpenSMILE toolkit (v2.1). The association of each acoustic feature with incident dementia was assessed by Cox proportional hazards models. Results: Our study included 6, 528 voice recordings from 4, 849 participants (mean age 63 ± 15 years old, 54.6% women). The majority of participants (71.2%) had one voice recording, 23.9% had two voice recordings, and the remaining participants (4.9%) had three or more voice recordings. Although all asymptomatic at the time of examination, participants who developed dementia tended to have shorter segments than those who were dementia free (P < 0.001). Additionally, 14 acoustic features were significantly associated with dementia after adjusting for multiple testing (P < 0.05 / 48 = 1 × 10–3). The most significant acoustic feature was jitterDDP_sma_de (P = 7.9 × 10–7), which represents the differential frame-to-frame Jitter. A voice based linear classifier was also built that was capable of predicting incident dementia with area under curve of 0.812. Conclusions: Multiple acoustic and linguistic features are identified that are associated with incident dementia among asymptomatic participants, which could be used to build better prediction models for passive cognitive health monitoring. Original Article Thu, 31 Dec 2020 00:00:00 GMT HonghuangLin, CodyKarjadi, Ting F. A.Ang, JoshiPrajakta, ChelseaMcManus, Tuka W.Alhanai, JamesGlass, RhodaAu, Thu, 31 Dec 2020 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100128 https://www.explorationpub.com/Journals/em/Article/100129 Silent coronary artery disease (CAD) is one of the manifestations of heart disease that particularly affects subjects with type 2 diabetes mellitus (T2DM). From a clinical point of view, silent CAD represents a constant challenge for the diabetologist, who has to decide whether a patient could or could not be screened for this disease. In the present narrative review, several aspects of silent CAD are considered: the epidemiology of the disease, the associated risk factors, and main studies conducted, in the last 20 years, especially aimed to demonstrate the usefulness of the screening of silent CAD, to improve cardiovascular outcomes in type 2 diabetes. Review Mon, 04 Jan 2021 00:00:00 GMT Saula Vigilide Kreutzenberg, Mon, 04 Jan 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100129 https://www.explorationpub.com/Journals/em/Article/100130 Patients submitted to liver transplantation (LT) are exposed to high risk of cardiovascular (CV) complications which are the main determinants of both short-term and long-term morbidity and mortality in LT. Non-alcoholic fatty liver disease (NAFLD) is a very frequent condition in general population and is associated with a high risk of cardiovascular disease (CVD) which represents the first cause of death of these patients. NAFLD is predicted to become the first indication to LT and nowadays is also frequently detected in patients submitted to LT for other indications. Thus, the risk of CVD in patients submitted to LT is forecasted to increase in the next years. In this review the extent of CV involvement in patients submitted to LT and the role of NAFLD, either recurring after transplantation or as de novo presentation, in increasing CV risk is analysed. The risk of developing metabolic alterations, including diabetes, hypertension, dyslipidemia and weight gain, all manifestations of metabolic syndrome, occurring in the first months after LT, is depicted. The different presentations of cardiac involvement, represented by early atherosclerosis, coronary artery disease, heart failure and arrhythmias in patients with NAFLD submitted to LT is described. In addition, the tools to detect cardiac alterations either before or after LT is reported providing the possibility for an early diagnosis of CVD and an early therapy able to reduce morbidity and mortality for these diseases. The need for long-term concerted multidisciplinary activity with dietary counseling and exercise combined with drug treatment of all manifestations of metabolic syndrome is emphasized. Review Tue, 02 Feb 2021 00:00:00 GMT RosaLombardi, GiuseppinaPisano, SilviaFargion, Anna LudovicaFracanzani, Tue, 02 Feb 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100130 https://www.explorationpub.com/Journals/em/Article/100131 In recent years, cancer immunotherapy has received unprecedented attention due to the clinical achievements. The applications of biomedical engineering and materials science to cancer immunotherapy have solved the challenges caused by immunotherapy to a certain extent. Among them, cell-derived vesicles are natural biomaterials chosen as carriers or immune-engineering in view of their many unique advantages. This review will briefly introduce the recent applications of cell-derived vesicles for cancer immunotherapy. Review Mon, 01 Mar 2021 00:00:00 GMT JialuXu, ChaoWang, Mon, 01 Mar 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100131 https://www.explorationpub.com/Journals/em/Article/100132 Aim: Substance use disorders (SUD) result in substantial morbidity and mortality worldwide. Opioids, and to a lesser extent cocaine, contribute to a large percentage of this health burden. Despite their high heritability, few genetic risk loci have been identified for either opioid or cocaine dependence (OD or CD, respectively). A genome-wide association study of OD and CD related phenotypes reflecting the time between first self-reported use of these substances and a first DSM-IV dependence diagnosis was conducted. Methods: Cox proportional hazards regression in a discovery sample of 6,188 African-Americans (AAs) and 6,835 European-Americans (EAs) participants in a genetic study of multiple substance dependence phenotypes were used to test for association between genetic variants and these outcomes. The top findings were tested for replication in two independent cohorts. Results: In the discovery sample, three independent regions containing variants associated with time to dependence at P < 5 × 10−8 were identified, one (rs61835088 = 1.03 × 10−8) for cocaine in the combined EA-AA meta-analysis in the gene FAM78B on chromosome 1, and two for opioids in the AA portion of the sample in intergenic regions of chromosomes 4 (rs4860439, P = 1.37 × 10−8) and 9 (rs7032521, P = 3.30 × 10−8). After meta-analysis with data from the replication cohorts, the signal at rs61835088 improved (HR = 0.87, P = 3.71 × 10−9 and an intergenic SNP on chromosome 21 (rs2825295, HR = 1.14, P = 2.57 × 10−8) that missed the significance threshold in the AA discovery sample became genome-wide significant (GWS) for CD. Conclusions: Although the two GWS variants are not in genes with obvious links to SUD biology and have modest effect sizes, they are statistically robust and show evidence for association in independent samples. These results may point to novel pathways contributing to disease progression and highlight the utility of related phenotypes to better understand the genetics of SUDs. Original Article Mon, 01 Mar 2021 00:00:00 GMT RichardSherva, CongcongZhu, LeahWetherill, Howard J.Edenberg, EmmaJohnson, LouisaDegenhardt, ArpanaAgrawal, Nicholas G.Martin, ElliotNelson, Henry R.Kranzler, JoelGelernter, Lindsay A.Farrer, Mon, 01 Mar 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100132 https://www.explorationpub.com/Journals/em/Article/100133 Aim: Popularity of electronic cigarettes (i.e. e-cigarettes) is soaring in Canada. Understanding person-level correlates of current e-cigarette use (vaping) is crucial to guide tobacco policy, but prior studies have not fully identified these correlates due to model overfitting caused by multicollinearity. This study addressed this issue by using classification tree, a machine learning algorithm. Methods: This population-based cross-sectional study used the Canadian Tobacco, Alcohol, and Drugs Survey (CTADS) from 2017 that targeted residents aged 15 or older. Forty-six person-level characteristics were first screened in a logistic mixed-effects regression procedure for their strength in predicting vaper type (current vs. former vaper) among people who reported to have ever vaped. A 9:1 ratio was used to randomly split the data into a training set and a validation set. A classification tree model was developed using the cross-validation method on the training set using the selected predictors and assessed on the validation set using sensitivity, specificity and accuracy. Results: Of the 3,059 people with an experience of vaping, the average age was 24.4 years (standard deviation = 11.0), with 41.9% of them being female and 8.5% of them being aboriginal. There were 556 (18.2%) current vapers. The classification tree model performed relatively well and suggested attraction to e-cigarette flavors was the most important correlate of current vaping, followed by young age (< 18) and believing vaping to be less harmful to oneself than cigarette smoking. Conclusions: People who vape due to flavors are associated with very high risk of becoming current vapers. The findings of this study provide evidence that supports the ongoing ban on flavored vaping products in the US and suggests a similar regulatory intervention may be effective in Canada. Original Article Mon, 01 Mar 2021 00:00:00 GMT RuiFu, NicholasMitsakakis, MichaelChaiton, Mon, 01 Mar 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100133 https://www.explorationpub.com/Journals/em/Article/100134 Aims: Prior research employing a standard backward digit span test has been successful in operationally defining neurocognitive constructs associated with the Fuster’s model of executive attention. The current research sought to test if similar behavior could be obtained using a cross-modal mental manipulation test. Methods: Memory clinic patients were studied. Using Jak-Bondi criteria, 24 patients were classified with mild cognitive impairment (MCI), and 33 memory clinic patients did not meet criteria for MCI (i.e. non-MCI). All patients were assessed with the digital version of the WRAML-2 Symbolic Working Memory Test-Part 1, a cross-modal mental manipulation task where patients hear digits, but respond by touching digits from lowest to highest on an answer key. Only 4 and 5-span trials were analyzed. Using an iPad, all test stimuli were played; and, all responses were obtained with a touch key. Only correct trials were analyzed. Average time to complete trials and latency for each digit was recorded. Results: Groups did not differ when average time to complete 4-span trials was calculated. MCI patients displayed slower latency, or required more time to re-order the 1st and 3rd digits. Regression analyses, primarily involving initial and latter response latencies, were associated with better, but different underlying neuropsychological abilities. Almost no 5-span analyses were significant. Conclusions: This cross-modal test paradigm found no difference for total average time. MCI patients generated slower 1st and 3rd response latency, suggesting differences in time allocation to achieve correct serial order recall. Moreover, different neuropsychological abilities were associated with different time-based test components. These data extend prior findings using a standard backward digit span test. Differences in time epochs are consistent with constructs underlying the model of executive attention and help explain mental manipulation deficits in MCI. These latency measures could constitute neurocognitive biomarkers that track emergent disease. Original Article Mon, 01 Mar 2021 00:00:00 GMT SheinaEmrani, MelissaLamar, Catherine C.Price, SatyaBaliga, VictorWasserman, EmilyMatusz, RodSwenson, GaneshBaliga, David J.Libon, Mon, 01 Mar 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100134 https://www.explorationpub.com/Journals/em/Article/100135 Aim: Diabetic foot syndrome (DFS) is a complication of diabetes in which the presence of infections, ulceration and/or destruction of deep tissue associated with neuropathy, peripheral atherosclerosis and comorbidity affect the prognosis, the need for limb amputation and quality of life. Purpose of the present study is to report the features of patients with acute DFS admitted to our Diabetic Foot Unit tertiary Center in 2019. Methods: In all patients admitted, the approach was performed through a multidisciplinary team (Diabetic Foot Care Team) and described in a specific diagnostic-therapeutic-assistance program. Criteria of inclusion were presence of sepsis and/or suspected osteomyelitis and/or critical limb ischemia. Clinical features and interventions performed were registered. Primary endpoints were mortality and amputation (major, minor). Secondary endpoints were length of hospitalization, type of revascularization and duration of antibiotic therapy. Results: Among 75 consecutive patients (mean age 70.9 years) enrolled, prevalence of acute DFS was higher among men (M/F 3:1). Poor glycemic control [mean hemoglobin A1c (HbA1c) 67.9 ± 22.3 mmol/mol], long duration of diabetes (mean 19 ± 16.3 years), high low-density lipoprotein-cholesterol (mean 89.5 ± 45.1 mg/ dL) and obesity (mean Body Mass Index 30.2 ± 7.6 kg/m2) were common. Diabetes-related complications as peripheral arterial disease (PAD) (76%), ischemic heart disease (48%), retinopathy (40.5%), hepatic steatosis (50%), heart failure (17.8%) were present. During hospitalization, 21 subjects (28.4%) underwent lower limb amputations (overall rate of major amputation 4%), and 41.3% underwent percutaneous angioplasty. Long period of hospitalization (18.4 ± 7.9 days) and prolonged antibiotic therapy (23.9 ± 15.9 days) were observed. Major amputation was associated with C-reactive protein > 6.5 mg/dL (P = 0.03), osteomyelitis (P = 0.001), prior insulin therapy (P = 0.015). Conclusions: Male sex, co-morbidity, PAD, systemic inflammation and poor glycemic control are major features of acute hospitalized DFS. An approach through a multidisciplinary team is recommended in order to treat vascular and extra-vascular complications aimed at reducing mortality and at improving quality of life. Original Article Mon, 01 Mar 2021 00:00:00 GMT MauroMaurantonio, FilippoGabrielli, ClaudiaCastellano, AndreaCarla, PietroAndreone, LucaRoncucci, Mon, 01 Mar 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100135 https://www.explorationpub.com/Journals/em/Article/100136 Aims: Reduced pre-operative cognitive functioning in older adults is a risk factor for postoperative complications, but it is unknown if preoperative digitally-acquired clock drawing test (CDT) cognitive screening variables, which allow for more nuanced examination of patient performance, may predict lengthier hospital stay and greater cost of hospital care. This issue is particularly relevant for older adults undergoing transcatheter aortic valve replacement (TAVR), as this surgical procedure is chosen for intermediate-risk older adults needing aortic replacement. This proof of concept research explored if specific latency and graphomotor variables indicative of planning from digitally-acquired command and copy clock drawing would predict post-TAVR duration and cost of hospitalization, over and above age, education, American Society of Anesthesiologists (ASA) physical status classification score, and frailty. Methods: Form January 2018 to December 2019, 162 out of 190 individuals electing TAVR completed digital clock drawing as part of a hospital wide cognitive screening program. Separate hierarchical regressions were computed for the command and copy conditions of the CDT and assessed how a-priori selected clock drawing metrics (total time to completion, ideal digit placement difference, and hour hand distance from center; included within the same block) incrementally predicted outcome, as measured by R2 change significance values. Results: Above and beyond age, education, ASA physical status classification score, and frailty, only digitally-acquired CDT copy performance explained significant variance for length of hospital stay (9.5%) and cost of care (8.9%). Conclusions: Digital variables from clock copy condition provided predictive value over common demographic and comorbidity variables. We hypothesize this is due to the sensitivity of the copy condition to executive dysfunction, as has been shown in previous studies for subtypes of cognitive impairment. Individuals undergoing TAVR procedures are often frail and executively compromised due to their cerebrovascular disease. We encourage additional research on the value of digitally-acquired clock drawing within different surgery types. Type of cognitive impairment and the value of digitally-acquired CDT command and copy parameters in other surgeries remain unknown. Original Article Fri, 05 Mar 2021 00:00:00 GMT Margaret EllenoraWiggins, CatherineDion, ErinFormanski, AnisDavoudi, ShawnaAmini, Kenneth M.Heilman, DanaPenney, DanaRandall, Cynthia W.Garvan, George J.Arnaoutakis, PatrickTighe, David J.Libon, Catherine C.Price, Fri, 05 Mar 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100136 https://www.explorationpub.com/Journals/em/Article/100137 Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening drug reaction, which can affect multiple organs. Patients with DRESS syndrome and hepatic manifestations may present alterations ranging from mild hepatitis to acute liver failure. The diagnosis might be difficult, and the management of these patients is challenging. This report analyzes a series of five cases reporting the clinical presentation, which ranged from acute hepatitis to liver failure, and discussed their treatment. Case Report Tue, 27 Apr 2021 00:00:00 GMT Maria GabrielaDelgado, StefaniaCasu, MatteoMontani, FelixBrunner, NasserSemmo, AnnalisaBerzigotti, Jean FrançoisDufour, Tue, 27 Apr 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100137 https://www.explorationpub.com/Journals/em/Article/100138 Aim: The renal lesions–including severe acute kidney injury–are severe outcomes in severe acute respiratory syndrome coronavirus 2 infections. There are no reports regarding the influence of the nutritional status on the severity and progress of these lesions. Ageing is also an important risk factor. Methods: In the present study we compared the influence of overweight and undernutrition on the levels of renal angiotensin converting enzymes 1 and 2 (ACE and ACE2), which were evaluated by Western blotting. Since the renin-angiotensin-aldosterone system (RAAS) has been implicated in the progress of kidney failure during coronavirus disease 2019, the influence of Angiotensin-(3-4) [Ang-(3-4)] was investigated. Ang-(3-4) is the shortest angiotensin-derived peptide, which is considered the physiological antagonist of several Ang II effects. Results: Both overweight and undernutrition downregulate the levels of ACE2 without influence on the levels of ACE in proximal tubules from kidney rats. Administration of Ang-(3-4) upregulates ACE2 to levels above the control in overweight but not in undernourished rats. Conclusions: Chronic undernourishment and overnourishment conditions play a central role in the renal ACE/ACE2 balance, and that the role of RAAS is also different in overweight and undernutrition. Original Article Tue, 27 Apr 2021 00:00:00 GMT RafaelLuzes, HumbertoMuzi-Filho, AmauryPereira-Acácio, ThuanyCrisóstomo, AdalbertoVieyra, Tue, 27 Apr 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100138 https://www.explorationpub.com/Journals/em/Article/100139 Nucleolin (NCL) is a multifunctional nucleolar phosphoprotein harboring critical roles in cells such as cell proliferation, survival, and growth. The dysregulation and overexpression of NCL are related to various pathologic and oncological indications. These characteristics of NCL make it an ideal target for the treatment of various cancers. AS1411 is a synthetic quadruplex-forming nuclease-resistant DNA oligonucleotide aptamer which shows a considerably high affinity for NCL, therefore, being capable of inducing growth inhibition in a variety of tumor cells. The high affinity and specificity of AS1411 towards NCL make it a suitable targeting tool, which can be used for the functionalization of therapeutic payload-delivery nanosystems to selectively target tumor cells. This review explores the advances in NCL-targeting cancer therapy through AS1411-functionalized delivery nanosystems for the selective delivery of a broad spectrum of therapeutic agents. Review Fri, 30 Apr 2021 00:00:00 GMT Pooria SafarzadehKozani, Pouya SafarzadehKozani, Mohammad TariqMalik, Fri, 30 Apr 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100139 https://www.explorationpub.com/Journals/em/Article/100140 The limitations of current cancer treatments have stimulated the application of nanotechnology to develop more effective and safer cancer therapies. Remarkable progress has been made in the development of nanomedicine to overcome issues associated with conventional cancer treatment, including low drug solubility, insufficient targeting, and drug resistance. The modulation of nanoparticles allows the improvement of drug pharmacokinetics, leading to improved targeting and reduced side effects. In addition, nanoparticles can be conjugated to ligands that specifically target cancer cells. Furthermore, strategies that exploit tumor characteristics to locally trigger drug release have shown to increase targeted drug delivery. However, although some clinical successes have been achieved, most nanomedicines fail to reach the clinic. Factors that hinder clinical translation vary from the complexity of design, incomplete understanding of biological mechanisms, and high demands during the manufacturing process. Clinical translation might be improved by combining knowledge from different disciplines such as cell biology, chemistry, and tumor pathophysiology. An increased understanding on how nanoparticle modifications affect biological systems is pivotal to improve design, eventually aiding development of more effective nanomedicines. This review summarizes the key successes that have been made in nanomedicine, including improved drug delivery and release by polymeric nanoparticles as well as the introduction of strategies that overcome drug resistance. In addition, the application of nanomedicine in immunotherapy is discussed, and several remaining challenges addressed. Review Fri, 30 Apr 2021 00:00:00 GMT CarmenPaus, Robbertvan der Voort, AlessandraCambi, Fri, 30 Apr 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100140 https://www.explorationpub.com/Journals/em/Article/100141 Vascular aging, aortic stiffness and hypertension are mechanistically interrelated. The perspective presented here will focus mainly on the molecular mechanisms of age-associated increases in the stiffness of the vascular smooth muscle cell (VSMC). This review will highlight the mechanisms by which the VSMC contributes to disorders of vascular aging. Distinct functional sub-components of the vascular cell and the molecular mechanisms of the protein-protein interactions, signaling mechanisms and intracellular trafficking processes in the setting of the aging aorta will be detailed. Perspective Thu, 20 May 2021 00:00:00 GMT Lova PrasadareddyKajuluri, KuldeepSingh, Kathleen GMorgan, Thu, 20 May 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100141 https://www.explorationpub.com/Journals/em/Article/100142 Some have said that it is inappropriate and perhaps impossible to consider wave and Windkessel phenomena simultaneously. For 50 years, arterial hemodynamics has been dominated by the frequency-domain “impedance analysis” in which it was assumed that all variations in aortic pressure and flow were caused only by forward- and backward-going waves. This paper is a review of the results of incorporating the effects of Frank’s Windkessel. We have taken the view that measured aortic pressure is the sum of a Windkessel component and forward-going and backward-going wave components. When the Windkessel component is initially subtracted out, the pattern of propagation and reflection of wave components becomes clear. Furthermore, this analysis obviates the implications of impedance analysis that have not been explained satisfactorily. Review Thu, 01 Jul 2021 00:00:00 GMT John V.Tyberg, Thu, 01 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100142 https://www.explorationpub.com/Journals/em/Article/100143 Immunotherapy is a unique approach to treat cancer that targets tumours besides triggering the immune cells. It attempts to harness the supremacy and specificity of immune cells for the regression of malignancy. The key strategy of immunotherapy is that it boosts the natural defence and manipulates the immune system at both cellular and molecular levels. Long-lasting anti-tumour response, reduced metastasis, and recurrence can be achieved with immunotherapy than conventional treatments. For example, targeting cytotoxic T-lymphocyte antigen-4 (CTLA4) by monoclonal antibody is reported as an effective strategy against cancer progression in vivo and chimeric antigen receptor (CAR) modified T-cells are known to express a stronger anti-tumour activity. CTLA4 and CAR are, therefore, beneficial in cancer immunotherapy; however, in clinical settings, both are expensive and cause adverse side effects. Nanomaterials have augmented advantages in cancer immunotherapy, besides their utility in effective delivery and diagnostics. In particular, materials based on lipids, polymers, and metals have been sought-after for delivery technologies. Moreover, the surface of nanomaterials can be engineered using ligands, antigens, and antibodies to target immune cells. In this sense, checkpoint inhibitors, cytokines, agonistic antibodies, surface receptors, and engineered T-cells are promising to regulate the immune system against tumours. Therefore, emerging nanomaterials that can be used for the treatment of cancer is the prime focus of this review. The correlation of mode of administration and biodistribution of various nanomaterials is reviewed here. Besides, the acute and chronic side effects and outcome of clinical trials in the context of cancer immunotherapy are discussed. Review Thu, 01 Jul 2021 00:00:00 GMT Sureshbabu Ram KumarPandian, Clayton FernandoRencilin, KrishnanSundar, Thu, 01 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100143 https://www.explorationpub.com/Journals/em/Article/100144 Aim: Although clinicians primarily diagnose dementia based on a combination of metrics such as medical history and formal neuropsychological tests, recent work using linguistic analysis of narrative speech to identify dementia has shown promising results. We aim to build upon research by Thomas JA & Burkardt HA et al. (J Alzheimers Dis. 2020;76:905–2) and Alhanai et al. (arXiv:1710.07551v1. 2020) on the Framingham Heart Study (FHS) Cognitive Aging Cohort by 1) demonstrating the predictive capability of linguistic analysis in differentiating cognitively normal from cognitively impaired participants and 2) comparing the performance of the original linguistic features with the performance of expanded features. Methods: Data were derived from a subset of the FHS Cognitive Aging Cohort. We analyzed a sub-selection of 98 participants, which provided 127 unique audio files and clinical observations (n = 127, female = 47%, cognitively impaired = 43%). We built on previous work which extracted original linguistic features from transcribed audio files by extracting expanded features. We used both feature sets to train logistic regression classifiers to distinguish cognitively normal from cognitively impaired participants and compared the predictive power of the original and expanded linguistic feature sets, and participants’ Mini-Mental State Examination (MMSE) scores. Results: Based on the area under the receiver-operator characteristic curve (AUC) of the models, both the original (AUC = 0.882) and expanded (AUC = 0.883) feature sets outperformed MMSE (AUC = 0.870) in classifying cognitively impaired and cognitively normal participants. Although the original and expanded feature sets had similar AUC, the expanded feature set showed better positive and negative predictive value [expanded: positive predictive value (PPV) = 0.738, negative predictive value (NPV) = 0.889; original: PPV = 0.701, NPV = 0.869]. Conclusions: Linguistic analysis has been shown to be a potentially powerful tool for clinical use in classifying cognitive impairment. This study expands the work of several others, but further studies into the plausibility of speech analysis in clinical use are vital to ensure the validity of speech analysis for clinical classification of cognitive impairment. Original Article Thu, 01 Jul 2021 00:00:00 GMT LarryZhang, AnthonyNgo, Jason A.Thomas, Hannah A.Burkhardt, Carolyn M.Parsey, RhodaAu, Reza HosseiniGhomi, Thu, 01 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100144 https://www.explorationpub.com/Journals/em/Article/100145 Aim: Impaired sleep quality and sleep oxygenation are common sleep pathologies. This study assessed the impact of these abnormalities on white matter (WM) integrity in an epidemiological cohort. Methods: The target population was the Framingham Heart Study Generation-2/Omni-1 Cohorts. Magnetic resonance imaging (diffusion tensor imaging) was used to assess WM integrity. Wearable digital devices were used to assess sleep quality: the (M1-SleepImageTM system) and the Nonin WristOx for nocturnal oxygenation. The M1 device collects trunk actigraphy and the electrocardiogram (ECG); sleep stability indices were computed using cardiopulmonary coupling using the ECG. Two nights of recording were averaged. Results: Stable sleep was positively associated with WM health. Actigraphic periods of wake during the sleep period were associated with increased mean diffusivity. One marker of sleep fragmentation which covaries with respiratory chemoreflex activation was associated with reduced fractional anisotropy and increased mean diffusivity. Both oxygen desaturation index and oxygen saturation time under 90% were associated with pathological directions of diffusion tensor imaging signals. Gender differences were noted across most variables, with female sex showing the larger and significant impact. Conclusions: Sleep quality assessed by a novel digital analysis and sleep hypoxia was associated with WM injury, especially in women. Original Article Thu, 01 Jul 2021 00:00:00 GMT Robert JosephThomas, HyunKim, PaulineMaillard, Charles S.DeCarli, Eric JamesHeckman, CodyKarjadi, Ting Fang AlvinAng, RhodaAu, Thu, 01 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100145 https://www.explorationpub.com/Journals/em/Article/100146 The renin-angiotensin system (RAS) is a key regulator of blood pressure and electrolyte homeostasis. Besides its importance as regulator of the cardiovascular function, the RAS has also been associated to the modulation of higher brain functions, including cognition, memory, depression and anxiety. For many years, angiotensin II (Ang II) has been considered the major bioactive component of the RAS. However, the existence of many other biologically active RAS components has currently been recognized, with similar, opposite, or distinct effects to those exerted by Ang II. Today, it is considered that the RAS is primarily constituted by two opposite arms. The pressor arm is composed by Ang II and the Ang II type 1 (AT1) receptor (AT1R), which mediates the vasoconstrictor, proliferative, hypertensive, oxidative and pro-inflammatory effects of the RAS. The depressor arm is mainly composed by Ang-(1-7), its Mas receptor (MasR) which mediates the depressor, vasodilatory, antiproliferative, antioxidant and anti-inflammatory effects of Ang-(1-7) and the AT2 receptor (AT2R), which opposes to the effects mediated by AT1R activation. Central Ang-(1-7) is implicated in the control of the cardiovascular function, thus participating in the regulation of blood pressure. Ang-(1-7) also exerts neuroprotective actions through MasR activation by opposing to the harmful effects of the Ang II/AT1R axis. This review is focused on the expression and regulation of the Ang-(1-7)/MasR axis in the brain, its main neuroprotective effects and the evidence regarding its involvement in the pathophysiology of several diseases at cardiovascular and neurological level. Review Thu, 01 Jul 2021 00:00:00 GMT Natalia L.Rukavina Mikusic, Angélica M.Pineda, Mariela M.Gironacci, Thu, 01 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100146 https://www.explorationpub.com/Journals/em/Article/100147 The adrenal cortex plays a key role in the regulation of metabolism, salt and water homeostasis and sex differentiation by synthesizing glucocorticoid, mineralocorticoid and androgen hormones. Evidence exists that angiotensin II regulates adrenocortical function and it has been contended that angiotensin peptides of the non-canonical branch of the renin angiotensin system (RAS) might also modulate steroidogenesis in adrenals. Thus, the aim of this review is to examine the role of the RAS, and particularly of the angiotensin peptides and their receptors, in the regulation of adrenocortical hormones with particular focus on aldosterone production. Review Thu, 01 Jul 2021 00:00:00 GMT Gian PaoloRossi, LiviaLenzini, BrasilinaCaroccia, GiacomoRossitto, Teresa MariaSeccia, Thu, 01 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100147 https://www.explorationpub.com/Journals/em/Article/100148 Not applicable. Commentary Mon, 19 Jul 2021 00:00:00 GMT GyorgyBaffy, Mon, 19 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100148 https://www.explorationpub.com/Journals/em/Article/100149 Obesity and metabolic syndrome are conditions at high risk for the development of complications such as type 2 diabetes mellitus, atherosclerotic cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). The growing prevalence of NAFLD has recently raised attention in the clinical practice, due to the worsening prognosis observed in the affected patients. Sex hormones abnormalities, commonly found in subjects suffering from obesity and metabolic syndrome, have been recently hypothesized to be directly involved in the physiopathology of obesity-related comorbidites; however, their role in the pathogenesis of NAFLD remains unclear. In this review of the available literature, a summary of the knowledge about the role of sex steroids abnormalities in the risk of developing NAFLD was performed, mentioning the possible clinical implications for therapy. Review Tue, 20 Jul 2021 00:00:00 GMT AngeloDi Vincenzo, LuciaRusso, Carlo GiovanniDoroldi, RobertoVettor, MarcoRossato, Tue, 20 Jul 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100149 https://www.explorationpub.com/Journals/em/Article/100150 Central pontine myelinolysis (CPM) is a rare manifestation of osmotic demyelination syndrome (ODS) which involves the pons and causes significant morbidity and mortality. CPM usually occurs in the setting of rapid correction of severe chronic hyponatremia. A rare case of CPM due to hyperglycemia in a 27-year-old man with type 1 diabetes is reported. During the patient’s hospitalization, his plasma glucose level showed a wide variability ranging from 38 mg/dL to 530 mg/dL; while plasma sodium level was constantly normal. At computed tomography (CT) scans, areas of hypodensity with a hyperdense ring were identified in the anterior part of the pons. At magnetic resonance imaging (MRI) scan, pontine abnormalities compatible with CPM were observed. According to laboratory tests, we concluded that CPM resulted from rapid and wide shifts in osmolar gradient owing to variability in plasma glucose levels. While universally recognized in several clinical settings, CPM is rarely observed in diabetic patients. Our report supports the notion that hyperosmolarity per se plays a key role in the pathogenesis of CPM, which may occur independently of sodium abnormalities. Case Report Tue, 17 Aug 2021 00:00:00 GMT StefaniaDi Agostino, Arianna A.C.Costanzo, PietroAndreone, MauroMaurantonio, Tue, 17 Aug 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100150 https://www.explorationpub.com/Journals/em/Article/100151 The term non-alcoholic fatty liver disease (NAFLD) appears unfitting both in adults and in children. As obesity and metabolic syndrome play a relevant pathogenic role, an international group of adults’ liver disease experts has proposed to rename this condition metabolic (dysfunction)-associated fatty liver disease (MAFLD). While this new more appropriate and useful definition has mostly been met with good reactions in adults, it may present a tangled path in pediatrics. Here we further stress the recommendations of the North American and the European Societies for Pediatric Gastroenterology, Hepatology and Nutrition that a hyperechogenic liver in a child affected by obesity or overweight with chronically elevated liver enzymes should not be assumed to have NAFLD only. Especially in those patients who are not in the classic age range or who have particularly severe laboratory anomalies, other genetic, metabolic (inborn errors of metabolism, IEM), endocrine, intestinal and hepatic pediatric-onset conditions, should in fact be excluded, particularly when response to a weight loss trial is not available. The term pediatric fatty liver disease (PeFLD) with three subtypes [1. contextual diagnosis of an IEM; 2. metabolic (dysfunction)-associated fatty liver; 3. unknown cause of fatty liver] has recently been proposed aiming to separate true MAFLD from IEM and/or the other above mentioned conditions, which may be rare when considered individually but represent a large group when considered collectively. Although the cost-effectiveness ratio of this attitude is still indeterminate, it is likely that the advantage of the early identification of a specifically treatable pediatric-onset liver disease associated to/mimicking MAFLD would be rewarding. Review Tue, 17 Aug 2021 00:00:00 GMT AngeloColucci, Maria ChiaraRocco, Anna Giulia ElenaDe Anseris, LuciaNazzaro, PietroVajro, ClaudiaMandato, Tue, 17 Aug 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100151 https://www.explorationpub.com/Journals/em/Article/100152 Submucosal esophageal hematoma is an uncommon clinical complication of anticoagulation. Current literature is scarce regarding presentation and management in acute submucosal hematomas in critically ill patients. Patients often present with retrosternal chest pain, making the diagnosis challenging due to overlap with common presentations of cardiopulmonary disorders. A high degree of suspicion is necessary in sedated patients. Several factors contribute to its etiology, and diagnosis often requires invasive techniques like endoscopy. However, management is usually supportive and aimed at its underlying cause. This is a case of a 68-year-old female who developed submucosal esophageal hematomas following anticoagulation for subarachnoid hemorrhage-related delayed neurological deficits in the intensive care unit. Case Report Fri, 20 Aug 2021 00:00:00 GMT HassamAli, MalihaNaseer, Fri, 20 Aug 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100152 https://www.explorationpub.com/Journals/em/Article/100154 The development of heart failure under various pathological conditions such as myocardial infarction (MI), hypertension and diabetes are accompanied by adverse cardiac remodeling and cardiac dysfunction. Since heart function is mainly determined by coordinated activities of different subcellular organelles including sarcolemma, sarcoplasmic reticulum, mitochondria and myofibrils for regulating the intracellular concentration of Ca2+, it has been suggested that the occurrence of heart failure is a consequence of subcellular remodeling, metabolic alterations and Ca2+-handling abnormalities in cardiomyocytes. Because of the elevated plasma levels of angiotensin II (ANG II) due to activation of the renin-angiotensin system (RAS) in heart failure, we have evaluated the effectiveness of treatments with angiotensin converting enzyme (ACE) inhibitors and ANG II type 1 receptor (AT1R) antagonists in different experimental models of heart failure. Attenuation of marked alterations in subcellular activities, protein content and gene expression were associated with improvement in cardiac function in MI-induced heart failure by treatment with enalapril (an ACE inhibitor) or losartan (an AT1R antagonist). Similar beneficial effects of ANG II blockade on subcellular remodeling and cardiac performance were also observed in failing hearts due to pressure overload, volume overload or chronic diabetes. Treatments with enalapril and losartan were seen to reduce the degree of RAS activation as well as the level of oxidative stress in failing hearts. These observations provide evidence which further substantiate to support the view that activation of RAS and high level of plasma ANG II play a critical role in inducing subcellular defects and cardiac dysfunction during the progression of heart failure. Review Tue, 31 Aug 2021 00:00:00 GMT Sukhwinder K.Bhullar, Anureet K.Shah, Naranjan S.Dhalla, Tue, 31 Aug 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100154 https://www.explorationpub.com/Journals/em/Article/100155 Aim: Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) immunization in patients with autoimmune diseases is of particular concern to understand their response to the infection and to the vaccine. In fact, the immunological disorder and the immunosuppressive therapies could affect the serological response. SARS-CoV2 serological tests potentially provide this information, although they were rapidly commercialized with internal verifications. Here, we analysed the seroprevalence to SARS-CoV2 in a cohort of patients with liver autoimmune diseases. Methods: From May to December 2020, a cohort of patients affected by primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and PBC/AIH overlap syndrome were screened with reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs, rapid antigenic test and chemiluminescent serological test during routine follow-up. Results: The analysis of 42 patients was carried out: 18 (42.85%) PBC, 12 (28.57%) AIH and 12 (28.57%) PBC/AIH overlap syndromes. Only 2 patients (4.76%) resulted positive to the RNA, antigen and antibody detection tests, hence affected by SARS-CoV2 infection. 14 subjects out of 40 negative cases presented a positive serology for SARS-CoV2 antibodies, hence with a false positivity in the 35% of cases without infection. Notably, among these, 6 (42.86%) patients presented only immunoglobulin (Ig)M positivity, 6 (42.86%) patients presented positivity for only IgG and 2 (14.28%) patients were positive to both IgM and IgG. Notably, the presence of autoantibodies did not correlate with the serological false positivity, highlighting that there is no cross-reactivity with autoantibodies. Moreover, the presence of polyclonal hypergammaglobulinemia did not interfere with the serological test as its prevalence is not different between negative and false positive cases. Interestingly, the patients with false positive serology showed higher levels of gamma-glutamyltransferase (GGT) and C-reactive protein (CRP). Conclusions: Patients with liver autoimmune diseases present a high rate of false positive SARS-CoV2 serology. Therefore, new strategies are needed to study the serological response in this patient category. Original Article Tue, 31 Aug 2021 00:00:00 GMT Maria GiuliaCornacchia, MorisSangineto, RosannaVillani, FrancescoCavallone, GiuseppeDi Gioia, PaolaCicciomessere, GaetanoServiddio, Tue, 31 Aug 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100155 https://www.explorationpub.com/Journals/em/Article/100153 Acute aortic syndromes, including aortic dissection (AD), are rare. The AD detection risk score (ADDRS) and associated investigation pathway were developed to reduce missed diagnosis of AD. The methodology for its development was sub-optimal and it has not been robustly validated in the emergency department chest pain population. Recent research suggests that it will drive over-investigation and that the risks of missed diagnosis may not be in balance with the risks of the testing strategy. There are serious doubts about whether the score and investigation pathway are fit for purpose. Perspective Tue, 31 Aug 2021 00:00:00 GMT Anne-MareeKelly, Tue, 31 Aug 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100153 https://www.explorationpub.com/Journals/em/Article/100156 Not applicable. Commentary Sat, 18 Sep 2021 00:00:00 GMT AlessandroMantovani, GiorgiaBeatrice, ChiaraZusi, AndreaDalbeni, Sat, 18 Sep 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100156 https://www.explorationpub.com/Journals/em/Article/100157 Aim: Smartphone technology is increasingly used by the public to assess sleep. Specific features of some sleep-tracking applications are comparable to actigraphy in objectively monitoring sleep. The clinical utility of smartphone apps should be investigated further to increase access to convenient means of monitoring sleep. Methods: Smartphone and subjective sleep measures were administered to 29 community-dwelling healthy adults [aged 20–67, Mean (M) = 26.8; 18 women, 11 men], and actigraphy to 19 of them. Total sleep time (TST) and sleep efficiency were measured with actigraphy and the Sleep Time App (Azumio Inc.). Sleep diaries captured subjective TST and sleep efficiency, and the Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index provided self-report data. An exit questionnaire was administered to examine App feasibility and likelihood of future use. Results: The App significantly overestimated TST when compared to actigraphy. There was no significant difference in sleep efficiency between methodologies. There was also no significant difference between TST recorded through the App and through sleep diaries. Participants’ self-reported ease of use of the smartphone App positively correlated with likelihood of future use. Conclusions: Based on the current findings, future research is needed to investigate the utility and feasibility of multiple smartphone applications in monitoring sleep in healthy and clinical populations. Original Article Mon, 27 Sep 2021 00:00:00 GMT TaylorMaynard, EricaAppleman, AliceCronin-Golomb, SandyNeargarder, Mon, 27 Sep 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100157 https://www.explorationpub.com/Journals/em/Article/100158 With the advent of various vaccines and antimicrobial agents during the 20th century, the control and containment of infectious diseases appeared to be a matter of time. However, studies unveiled the diverse natures of microbes, their lifestyle, and pathogenetic potentials. Since the ground-breaking discovery of the hepatitis B virus (HBV) by Baruch Blumberg and the subsequent development of a vaccine in the early 1980s, the main task of the scientific community has been to develop a proper management strategy for HBV-induced chronic liver diseases. In the early 1980’s, standard interferon (IFN) induced a reduction of HBV DNA levels, followed by the normalization of serum transaminases (alanine aminotransferase, ALT), in some chronic hepatitis B (CHB) patients. However, in the course of time, the limitations of standard IFN became evident, and the search for an alternative began. In the late 1980’s, nucleoside analogs entered the arena of CHB treatment as oral drugs with potent antiviral capacities. At the beginning of the 21st century, insights were developed into the scope and limitations of standard IFN, pegylated-IFN as well as nucleoside analogs for treating CHB. Considering the non-cytopathic nature of the HBV, the presence of covalently closed circular DNA (cccDNA) in the nucleus of the infected hepatocytes and HBV-induced immune-mediated liver damages, a new field of CHB management was initiated by modulating the hosts’ immune system through immune therapy. This review will discuss the nature and design of innovative immune therapy for CHB. Review Thu, 30 Sep 2021 00:00:00 GMT Sheikh Mohammad FazleAkbar, Mamun AlMahtab, Julio CesarAguilar, Md. HelalUddin, Md. Sakirul IslamKhan, OsamuYoshida, EduardoPenton, Guillen NietoGerardo, YoichiHiasa, Thu, 30 Sep 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100158 https://www.explorationpub.com/Journals/em/Article/100159 Aim: As the novel coronavirus disease 2019 (COVID-19) pandemic impacts the global healthcare system, evolving data show increased frequency of arterial and venous thromboembolism among patients with COVID-19 infection. Aortic thrombus is a rare thrombotic event with a wide spectrum of clinical manifestations and potential catastrophic complications. This study aimed to elucidate the clinical manifestations, diagnosis and treatment dilemmas of aortic thrombus with COVID-19 infection and raise awareness among frontline medical providers. Aortic thrombosis is rare, but if not considered early in the course of COVID-19 infection, the data suggest that the diagnosis will probably not be made until potentially serious complications arise. Methods: Literature review was conducted between November 1, 2019, and November 14, 2020, on PubMed and Embase to identify publications regarding aortic thrombosis among COVID-19 cases. Results: Most of the patients were male with a median age of 67 years, and had comorbidities (most commonly hypertension, dyslipidemia and diabetes mellitus). In our study, underlying atherosclerosis, a common risk factor for aortic thrombus, was identified among 56% of the patients. Aortic thrombus was symptomatic in 62% of these patients and most commonly manifested itself as acute limb ischemia (46%), whereas 30% of cases were found incidentally during the investigation of elevated inflammatory markers or increased oxygen requirement. Treatment was individualized given the lack of established guidelines for aortic thrombus, including anticoagulation, systemic and catheter directed thrombolysis, and surgical thrombectomy. Overall mortality was found to be 30% in our study. Conclusions: Although rare, aortic thrombus has high morbidity and mortality, and can present without any symptoms or underlying aortic disease. Aortic thrombosis is rare, but if not considered early in the course of COVID-19 infection, the data suggest that the diagnosis will probably not be made until potentially serious complications arise. Meta-Analysis Sat, 09 Oct 2021 00:00:00 GMT KorinKarabulut, AhmetKapici, AnaAndronikashvili, JamesMorgan, Sat, 09 Oct 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100159 https://www.explorationpub.com/Journals/em/Article/100160 Pregnancy increases the risk of common vascular events and also the rarer events like aortic dissection (AD)/aortic rupture and this is even more pronounced in patients with predisposing aortopathies. AD was found to occur in 0.0004% of all pregnancies, and it is more pronounced in patients with underlying connective tissue disorders. The normal hemodynamic changes on a weak aorta will lead to AD and/or rupture, more so with increase in the period of gestation. Hence the haemodynamic and hormonal changes during pregnancy make pregnancy itself a risk factor for AD. It is advised that women with Marfan syndrome who are planning pregnancy should go through prophylactic aortic repair if the diameter of the ascending aorta exceeds 4 cm. Pre-pregnancy counselling is very important in these patients and must include complete history taking, including family history, physical examination and advanced aortic imaging. There is a general consensus among various authors advising against surgery during pregnancy in stable patients due to increased maternal and fetal morbidity but it is justified if the condition is refractory to medical management or in life threatening stage like acute AD. Though the incidence of aortopathy in pregnancy is rare, there is a high maternal and fetal mortality associated with this condition. Review Mon, 01 Nov 2021 00:00:00 GMT PreethaRajasekaran, PraveenaGandhi, MohammedIdhrees, Bashi V.Velayudhan, Mon, 01 Nov 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100160 https://www.explorationpub.com/Journals/em/Article/100161 Recently, Arrese and Colleagues have published a review article entitled, “Insights into Nonalcoholic Fatty-Liver Disease (NAFLD) Heterogeneity” (Semin Liver Dis. 2021;41:421–34. doi: 10.1055/s-0041-1730927). This milestone publication clearly and exhaustively explains the multitude of pathogenic pathways involved in the development and progression of disease eventually conducive to heterogeneous clinical phenotypes and different disease outcomes. The present commentary first briefly discusses the biological grounds of NAFLD heterogeneity and then illustrates the work by Arrese et al. In conclusion, the presently adopted nomenclatures appear inadequate in rendering the complexity of disease in the individual patient. In order to adopt the principles of personalized care, what remains to be done is to propose and validate a simple and accurate classification system. This should give full consideration to the principal disease modifiers and should shape a scheme to be adopted in both clinical practice and in the research arena. Care should be taken to not neglect the systemic nature of disease. Commentary Mon, 01 Nov 2021 00:00:00 GMT AmedeoLonardo, Mon, 01 Nov 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100161 https://www.explorationpub.com/Journals/em/Article/100162 Excessive reactive oxygen species (ROS) may cause oxidative stress which is involved in aging and in the pathogenesis of various human diseases. Whereas unregulated levels of the ROS may be harmful, regulated basal level of ROS is even necessary to support cellular functions as a second messenger for homeostasis under physiological conditions. Therefore, redox medicine could develop as a new therapeutic concept for human health-benefits. Here, we introduce the involvement of ROS on the crossroads of stemness, senescence, and carcinogenesis in a stem cell and cancer cell biology. Amazingly, the anti-proliferative (APRO) family anti-proliferative proteins characterized by immediate early growth responsive genes may also be involved in the crossroads machinery. The biological functions of APRO proteins (APROs) seem to be quite intricate, however, which might be a key modulator of microRNAs (miRNAs). Given the crucial roles of ROS and APROs for pathophysiological functions, upcoming novel therapeutics should include vigilant modulation of the redox state. Next generation of medicine including regenerative medicine and/or cancer therapy will likely comprise strategies for altering the redox environment with the APROs via the modulation of miRNAs as well as with the regulation of ROS of cells in a sustainable manner. Perspective Mon, 01 Nov 2021 00:00:00 GMT YukaIkeda, KurumiTaniguchi, NozomiNagase, AiTsuji, YasukoKitagishi, SatoruMatsuda, Mon, 01 Nov 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100162 https://www.explorationpub.com/Journals/em/Article/100163 According to the Global Cancer Observatory (GLOBOCAN) 2020, colorectal carcinoma (CRC) was the second leading cause of cancer death globally. Current literature utilizes reported databases such as Surveillance, Epidemiology, and End Results (SEER) to better understand the epidemiology of CRC. The global cancer observatory’s “Cancer Tomorrow” data visualization tools were used to predict the future incidence and mortality of colorectal cancers until 2030 as a guided tool to look over ways to reduce incidence by controlling risk factors of CRC. The total number of CRC is expected to rise by 2030, with a percent change of 17.3%. The expected percent change in colon cancer is more than rectal cancer (19.8% vs. 11.6%). The estimated number of deaths secondary to CRC is expected to increase in 2030, an estimated percent change of 22.2%. The incidence and mortality rate was higher in men vs. women; however, the gap seems to be closing on trend analysis. Major risk factors for CRC include familial syndromes, family history, race, gender, obesity, diet, alcohol, and smoking. Risk can be reduced by exercise and dietary changes, fiber intake, vitamin D, calcium, and minerals. Individualized screening based on age, gender, and additional risk factors could be an option that needs further comparative data to propose a definitive benefit over established screening guidelines. Review Tue, 23 Nov 2021 00:00:00 GMT HassamAli, Tue, 23 Nov 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100163 https://www.explorationpub.com/Journals/em/Article/100164 Antenatal screening for hepatitis B surface antigen seropositivity is widely adopted to identify pregnant women with chronic hepatitis B virus (HBV) infection in order to target their newborn infants for combined passive-active neonatal immunization to prevent the maternal-to-child transmission of HBV. It is less certain whether the presence of chronic HBV infection in these largely asymptomatic women could impact their pregnancy outcome. There is now gathering information in the literature, though sometimes conflicting, on the obstetric implications of chronic HBV infection. The conflicting data is most probably related to confounding factors such as the immunological phase of chronic HBV infection, viral genotype and activity, presence of hepatic inflammation and other co-existing liver disorders such as non-alcoholic fatty liver disease, and coinfection with other virus such as hepatitis C virus and micro-organisms, which are usually not examined, but which could have made significant influence on the occurrence of many of the pregnancy complications and adverse fetal and neonatal outcome. For pregnancy complications, the evidence suggests association with increased gestational diabetes mellitus, preterm birth, intrahepatic cholestasis of pregnancy, caesarean delivery, and postpartum haemorrhage, probably increased placental abruption and prelabour rupture of the membranes, and no effect or a reduction in the hypertensive disorders of pregnancy, especially preeclampsia. For perinatal outcome, there may be increased miscarriage and fetal malformations, and increase in both low birthweight and large-for-gestational age/macrosomic infants, as well as increased intrauterine fetal demise/stillbirth and fetal distress. However, most studies have not elaborated on the mechanisms or explanations of many of the adverse outcomes. Taken together, maternal chronic HBV infection increases the risk of adverse obstetric outcome overall, but further prospective studies are warranted to elucidate the reasons and mechanisms of, and with a view to mitigating, these adverse obstetric outcomes. Review Tue, 30 Nov 2021 00:00:00 GMT Terence T.Lao, Tue, 30 Nov 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100164 https://www.explorationpub.com/Journals/em/Article/100165 Aim: The high heterogeneity in the definitions of low back pain encountered in the literature has led to the development of standardized definitions of this condition called “Delphi definitions of low back pain prevalence (Delphi DOLBaPP)” by a group of international researchers. In order to be widely used, these definitions need to be adapted according to the cultural and linguistic context. The aim of this work was to perform the cross-cultural adaptation of the Delphi DOLBaPP definitions in Quebec French and to pre-test them among French-speaking adults. Methods: In order to enable practical use of the Delphi DOLBaPP definitions in different contexts, their presentation was adapted in the form of a questionnaire (referred to as the “Delphi DOLBaPP questionnaire”). The process of cross-cultural adaptation of the Delphi DOLBaPP questionnaire in French was conducted according to the most recognized recommendations for the cultural adaptation of measuring instruments. The resulting questionnaire and an evaluation form were then submitted to a sample of 82 adults. Results: A total of 41 participants (50.0%) reported low back pain. A high proportion of participants (89.0%) stated that it took them less than 5 minutes to complete the questionnaire. More than 62.0% of them did not find any question poorly worded or confusing. Nearly 80.0% of the participants found the questionnaire easy to understand. The cross-cultural adaptation process suggested minor modifications to the original Delphi DOLBaPP questionnaire. Conclusions: This study has produced a cross-cultural adaptation of the Delphi DOLBaPP questionnaire in Quebec French that will enable French-speaking populations to share the benefits of using standardized definitions of low back pain in epidemiological studies. Original Article Tue, 07 Dec 2021 00:00:00 GMT AntarouLy, SylviePelletier, Clermont E.Dionne, Tue, 07 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100165 https://www.explorationpub.com/Journals/em/Article/100166 Non-alcoholic fatty liver disease (NAFLD) as the most common chronic liver disease poses a significant impact on public healthcare and economic risk worldwide. As a multifactorial disease, NAFLD is usually associated with many comorbidities such as obesity, insulin resistance, hypertension, hyperlipidemia, diabetes, and cardiovascular disease. Without effectively preventive intervention, the advanced stage of NAFLD, non-alcoholic steatohepatitis (NASH), can progress to cirrhosis and hepatocellular carcinoma (HCC). However, there is no approved therapeutic treatment. Excessive fat accumulation in the liver is the hallmark of NAFLD, which can lead to mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Dysfunction of two organelles also induces the upregulation of reactive oxygen species (ROS), activation of the unfolded protein response (UPR), and disruption of calcium transport, which promote NAFLD progression. Herein, this review summarized the current understanding of the roles of mitochondrial dysfunction and ER stress in the pathogenesis of NAFLD. Specifically, this review focused on the key molecules associated with the ER-mitochondria communication and different treatment options by targeting ER stress and mitochondrial dysfunction to treat NAFLD or NASH. Clinical trials to evaluate the therapeutic efficacy of representative agents, such as natural products, metabolites, and modulators of stress, have been reviewed and analyzed. Overall, recent findings suggest that targeting ER stress and mitochondrial dysfunction holds a promise for NAFLD treatment. Review Wed, 08 Dec 2021 00:00:00 GMT ChunyeZhang, MingYang, Wed, 08 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100166 https://www.explorationpub.com/Journals/em/Article/100167 Tissue-resident macrophages play critically important roles in host homeostasis and pathogenesis of diseases, with the functions of phagocytosis, metabolism, and immune modulation. Recently, two research studies accomplished by a collaborated group of researchers showed that there are two populations of liver resident Kupffer cells (KCs), including a major cluster of differentiation 206 low expression (CD206low)endothelial cell-selective adhesion molecule negative (ESAM−) population (KC1) and a minor CD206highESAM+ population (KC2). Both KC1 and KC2 express KC markers, such as C-type lectin domain family 4 member F (CLEC4F) and T-cell membrane protein 4 (Tim4). In fatty liver, the frequency of KC2 was increased, and those KC2 expressed some markers like liver sinusoidal endothelial cells (LSECs), such as CD31 and ESAM. In addition, KC2 population had a relatively higher expression of CD36, as fatty acid transporter, which was implicated in the production of reactive oxygen species (ROS) and lipid peroxidation. Furthermore, this collaborated group also showed that KC2 can cross-present hepatocellular antigens to prime antiviral function of CD8+ T cells by sensing interleukin-2 (IL-2) in hepatitis B virus (HBV) replication-competent transgenic mice. Increasing evidence shows that targeting hepatic macrophages can prevent and reverse non-alcoholic fatty liver disease (NAFLD), with a new suggested name metabolic dysfunction-associated fatty liver disease (MAFLD) to include metabolic dysfunction-associated fatty liver diseases, such as viruses and alcohol. In summary, differentiating specific populations of hepatic macrophages is critically important for the treatment of MAFLD or NAFLD, and their overlaps. Markers specifically expressed on sub-types of hepatic macrophages may be applied for liver disease diagnosis. Commentary Wed, 15 Dec 2021 00:00:00 GMT ChunyeZhang, ShuaiLiu, MingYang, Wed, 15 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100167 https://www.explorationpub.com/Journals/em/Article/100168 The processes of cancer and embryonic development have a partially overlapping effect. Several transcription factor families, which are highly conserved in the evolutionary history of biology, play a key role in the development of cancer and are often responsible for the pivotal developmental processes such as cell survival, expansion, senescence, and differentiation. As an evolutionary conserved and ubiquitously expression protein, CCCTC-binding factor (CTCF) has diverse regulatory functions, including gene regulation, imprinting, insulation, X chromosome inactivation, and the establishment of three-dimensional (3D) chromatin structure during human embryogenesis. In various cancers, CTCF is considered as a tumor suppressor gene and plays homeostatic roles in maintaining genome function and integrity. However, the mechanisms of CTCF in tumor development have not been fully elucidated. Here, this review will focus on the key roles of CTCF in cancer evolution and development (Cancer Evo-Dev) and embryogenesis. Review Fri, 24 Dec 2021 00:00:00 GMT ZishuaiLi, XinyuZhou, ShiliangCai, JunyanFan, ZhiminWei, YifanChen, GuangwenCao, Fri, 24 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100168 https://www.explorationpub.com/Journals/em/Article/100169 Pseudoexfoliation (PXF) syndrome is an important public health concern requiring individual population level analysis. Disease prevalence differs by geographic location and ethnicity, and has environmental, demographic, genetic, and molecular risk factors have been demonstrated. Epidemiological factors that have been associated with PXF include age, sex, environmental factors, and diet. Genetic and molecular components have also been identified that are associated with PXF. Underserved populations are often understudied within scientific research, including research about eye disease such as PXF, contributing to the persistence of health disparities within these populations. In each population, PXF needs may be different, and by having research that identifies individual population needs about PXF, the resources in that population can be more efficiently utilized. Otherwise, PXF intervention and care management based only on the broadest level of understanding may continue to exacerbate health disparities in populations disproportionally burdened by PXF. Review Fri, 31 Dec 2021 00:00:00 GMT Patrice M.Hicks, AdamSiedlecki, BenjaminHaaland, Leah A.Owen, ElizabethAu, MichaelFeehan, Maureen A.Murtaugh, SandraSieminski, AndrewReynolds, JohnLillvis, Margaret M.DeAngelis, Fri, 31 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100169 https://www.explorationpub.com/Journals/em/Article/100170 Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a fundamental role in regulating endothelial function and vascular tone in the physiological conditions of a vascular system. However, oxidative stress has detrimental effects on human health, and numerous studies confirmed that high ROS/RNS production contributes to the initiation and progression of cardiovascular diseases. The antioxidant defense has an essential role in the homeostatic functioning of the vascular endothelial system. Endogenous antioxidative defense includes various molecules and enzymes such as superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. Together all these antioxidative enzymes are essential for defense against harmful ROS features. ROS are mainly generated from redox-active compounds involved in the mitochondrial respiratory chain. Thus, targeting antioxidative enzymes and mitochondria oxidative balance may be a promising approach for vascular diseases occurrence and treatment. This review summarized the most recent research on the regulation of antioxidative enzymes in vascular diseases. Review Fri, 31 Dec 2021 00:00:00 GMT JelenaRadovanovic, KatarinaBanjac, MilanObradovic, Esma R.Isenovic, Fri, 31 Dec 2021 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100170 https://www.explorationpub.com/Journals/em/Article/100171 Aim: Isolated specific glycone–aglycone conjugated flavonoids which are investigated for their effect of bioavailability and molecular concentrations. The specific formula is then tested via in vitro and in vivo cytotoxicity tests. Methods: Considering the higher affinity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), quercetin, quercetin 3-sambubioside-3’-glucoside, luteolin, apigenin-7-4’alloside, kaempferol-7-O-glucoside, epicatechin-epigallocatechin-3-O-gallate, and hesperetin were selected to investigate the effects of a new combination of the formula. Specific chemical analyses, such as high-performance liquid chromatography (HPLC), liquid chromatography–mass spectrometry (LC–MS), quadrupole time of flight mass spectrometry (QTOF–MS) analysis and ultraviolet–visible (UV–VIS) spectrophotometry, were performed for molecular qualification and quantification. Results: In silico molecular docking analyses have shown that flavonoids can bind strongly to the spike protein and main protease of the SARS-CoV-2 virus. Flavonoids also have anti-inflammatory and immune-modulating activity by inhibiting cytokines. Although flavonoids may be a treatment alternative for coronavirus disease 2019 (COVID-19), an effective flavonoid compound has yet to be developed. The main problem here is that the absorption rate of flavonoids is very low (2–10%) in the intestines, and these compounds are metabolized rapidly. In contrast, according to recent literature, a conjugated flavonoid mixture is better absorbed in the small intestine, and its toxic effects are relatively fewer. Conclusions: It is found that the new formula has no cytotoxic or genotoxic effects. Furthermore, oral administrations of the new compound did not produce any toxicity symptoms or any mortality in male and female rats. The pre-clinical in vitro and in vivo toxicity test results indicated that the new flavonoid formula can be safely used for clinical trials. Original Article Wed, 19 Jan 2022 00:00:00 GMT Gürer G.Budak, SeçilÖzkan, MehmetBudak, TamayŞeker, BaharMeryemoglu, Şükran SelinMiran, Canan ÇakırÇoban, OrkunTarkun, Wed, 19 Jan 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100171 https://www.explorationpub.com/Journals/em/Article/100172 Cancer is the leading cause of mortality worldwide, which necessitates our consideration related to novel treatment approach. Tumor cells at the tumor microenvironment (TME), regulate a plethora of key mechanistic signaling pathways that obstruct antitumor immune responses by immune suppression, immune resistance or acquired immune tolerance. The present therapeutic regimes are provided independently or in combination, or as immunotherapies for cancer immune targeting. Immunotherapy has altered the arena of oncology and patient care. By using the host immune system, the immunostimulatory molecules can exert a robust, personalized response against the patient’s own tumors. Alternatively, tumors may exploit these strategies to escape immune recognition, and accordingly, such mechanisms represent chances for immunotherapy intervention. Nonetheless, despite promising outcomes from immunotherapies in recurrent and metastatic cancers, immune-therapeutics in clinics have been limited owing to unpredictability in the produced immune response and reported instances of immune-related adverse effects. The unrealized potential of immunotherapies in cancer management maybe due to the obstacles such as heterogeneous nature, multiple targets, patients’ immune response, specificity for cancer or variability in response generation in toxicity levels, delivery and cost related to therapeutics etc. Further revolutionary trends related to immunotherapies are noticeable with slower progress for cancer management. Recent advances in nanomedicine strategize to ameliorate the lacuna of immunotherapy as it relies on the inherent biophysical characteristics of nanocarriers: size, shape, surface charge and multifunctionality and exploiting them as first line therapy for delivery of biomolecules, single checkpoint inhibitors and for imaging of TME. Therefore, nano-assisted immunotherapies can boost the immunotherapeutic approach, overcoming factors that are with imminent potential risks related to it, thereby significantly improving the survival rate associated with it in cancer patients. Nanotechnology is anticipated to overcome the confines of existing cancer immunotherapy and to successfully combine various cancer treatment modes. Review Wed, 16 Feb 2022 00:00:00 GMT PriyankaSingh, MonikaYadav, KarishmaNiveria, Anita KamraVerma, Wed, 16 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100172 https://www.explorationpub.com/Journals/em/Article/100173 The redox status in pathogenesis is critically regulated by careful balance between the generation of reactive oxygen species (ROS) and their elimination. Increased ROS level above the cellular tolerability threshold results in apoptotic or necrotic cell death. ROS belongs to a group of highly reactive compounds that have evolved to play key roles in cellular signaling pathways. It’s widely assumed that a reasonable amount of ROS is essential for a variety of biological processes. Elevated levels of ROS are known to cause various pathologic conditions like neurological disorders, cardiovascular conditions, inflammation, autoimmunity, and cancer. ROS is well known to initiate and assist in progression of tumor by promoting proliferation and survival of cancer cells and thus facilitates pro-tumorigenic signaling in tumor microenvironment. As cancer cells become more resilient to the effects of ROS manipulating drugs, increased antioxidant capacity attenuates their susceptibility to cancer treatment. Excessive environmental stress, on the other hand, can cause cancer cells to die. This review summarizes various molecular mechanisms including the role of checkpoint inhibitors that can be harnessed to develop effective therapeutic strategies for targeting ROS related signaling in cancer. Review Tue, 22 Feb 2022 00:00:00 GMT RanjeetSingh, Partha PratimManna, Tue, 22 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100173 https://www.explorationpub.com/Journals/em/Article/100174 Since obesity is one of the main factors in the development of insulin resistance (IR) and is also associated with increased oxidative stress (OxS) rate, this study aims to review the published literature to collate and provide a comprehensive summary of the studies related to the status of the OxS in the pathogenesis of obesity and related IR. OxS represents an imbalance between the production of reactive oxygen and nitrogen species (RONS) and the capacity of the antioxidant defense system (AOS) to neutralize RONS. A steady-state of RONS level is maintained through endogenous enzymatic and non-enzymatic AOS components. Three crucial enzymes, which suppress the formation of free radicals, are superoxide dismutases, catalases, and glutathione peroxidases. The second line of AOS includes non-enzymatic components such as vitamins C and E, coenzyme Q, and glutathione which neutralizes free radicals by donating electrons to RONS. Emerging evidence suggests that high RONS levels contribute to the progression of OxS in obesity by activating inflammatory pathways and thus leading to the development of pathological states, including IR. In addition, decreased level of AOS components in obesity increases the susceptibility to oxidative tissue damage and further progression of its comorbidities. Increased OxS in accumulated adipose tissue should be an imperative target for developing new therapies in obesity-related IR. Review Wed, 23 Feb 2022 00:00:00 GMT AnastasijaPanic, JulijanaStanimirovic, EminaSudar-Milovanovic, Esma R.Isenovic, Wed, 23 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100174 https://www.explorationpub.com/Journals/em/Article/100175 Not applicable. Editorial Fri, 25 Feb 2022 00:00:00 GMT DanteRomagnoli, Fri, 25 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100175 https://www.explorationpub.com/Journals/em/Article/100176 T cells play a central role in anti-tumor immunity, and reactive oxygen species (ROS) lie at the crossroad on the anti-tumor T cell responses. To activate efficient T cell immunity, a moderate level of ROS is needed, however, excessive ROS would cause toxicity to the T cells, because the improper level leads to the formation and maintenance of an immunosuppressive tumor microenvironment. Up to date, strategies that modulate ROS, either increasing or decreasing, have been widely investigated. Some of them are utilized in anti-tumor therapies, showing inevitable impacts on the anti-tumor T cell immunity with both obverse and reverse sides. Herein, the impacts of ROS-increasing and ROS-decreasing treatments on the T cell responses in the tumor microenvironment are reviewed and discussed. At the same time, outcomes of combination immunotherapies are introduced to put forward inspirations to unleash the potential of immunotherapies. Review Fri, 25 Feb 2022 00:00:00 GMT TaoWang, HaiyanXu, Fri, 25 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100176 https://www.explorationpub.com/Journals/em/Article/100177 Aim: Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with activated CD4+ T cells and autoantibodies to angiotensin II type 1 receptor (AT1-AA). We have previously shown that CD4+ T cells isolated from women with PE cause hypertension, increased tumor necrosis factor alpha (TNF-α), endothelin-1, and soluble fms-like tyrosine kinase-1 (sFlt-1) when injected into pregnant nude-athymic rats compared to CD4+ T cells from normal pregnant (NP) women. However, the role of PE CD4+ T cells to cause AT1-AA as a mechanism of hypertension is not known. Our goal was to determine if PE CD4+ T cells stimulate AT1-AA in pregnant nude-athymic rats. Methods: CD4+ T cells were isolated from human NP and PE placentasand injected into nude-athymic rats on gestational day (GD) 12. In order to examine the role of the PE CD4+ T cells to stimulate B cell secretion of AT1-AA, a subset of the rats receiving PE CD4+ T cells were treated with rituximab on GD 14 or anti-CD40 ligand (anti-CD40L) on GD 12. On GD 19, mean arterial pressure (MAP) and tissues were obtained. Results: MAP [114 ± 1 mmHg (n = 9)] and AT1-AA [19.8 ± 0.9 beats per minute (bpm, n = 4)] were increased in NP nude + PE CD4+ T cells compared to NP nude + NP CD4+ T cells [98 ± 2 mmHg (n = 7, P < 0.05) and 1.3 ± 0.9 bpm (n = 5, P < 0.05)]. Rituximab (103 ± 2 mmHg, n = 3, P < 0.05) and anti-CD40L (102 ± 1 mmHg, n = 3, P < 0.05) lowered MAP compared to NP nude + PE CD4+ T cells. Circulating a proliferation-inducing ligand (APRIL) and placental angiotensin-converting enzyme 2 (ACE-2) activity was increased in response to PE CD4+ T cells. Conclusions: These results show that placental CD4+ T cells play an important role in the pathophysiology of PE, by activating B cells secreting AT1-AA to cause hypertension during pregnancy. Original Article Fri, 25 Feb 2022 00:00:00 GMT Kristin E.Reeve, EvangelineDeer, Lorena M.Amaral, Denise C.Cornelius, OwenHerrock, Ashlyn C.Harmon, NathanCampbell, SarahFitzgerald, TarekIbrahim, GerdWallukat, RalfDechend, BabbetteLaMarca, Fri, 25 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100177 https://www.explorationpub.com/Journals/em/Article/100178 Melatonin is the primary hormone of the pineal gland that is secreted at night. It regulates many physiological functions, including the sleep-wake cycle, gonadal activity, free radical scavenging, immunomodulation, neuro-protection, and cancer progression. The precise functions of melatonin are mediated by guanosine triphosphate (GTP)-binding protein (G-protein) coupled melatonin receptor 1 (MT1) and MT2 receptors. However, nuclear receptors are also associated with melatonin activity. Circadian rhythm disruption, shift work, and light exposure at night hamper melatonin production. Impaired melatonin level promotes various pathophysiological changes, including cancer. In our modern society, breast cancer is a serious problem throughout the world. Several studies have been indicated the link between low levels of melatonin and breast cancer development. Melatonin has oncostatic properties in breast cancer cells. This indolamine advances apoptosis, which arrests the cell cycle and regulates metabolic activity. Moreover, melatonin increases the treatment efficacy of cancer and can be used as an adjuvant with chemotherapeutic agents. Review Fri, 25 Feb 2022 00:00:00 GMT Naba KumarDas, SaptadipSamanta, Fri, 25 Feb 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100178 https://www.explorationpub.com/Journals/em/Article/100179 Aim: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed less new-onset atrial fibrillation (AF) in hypertensive patients receiving losartan- vs. atenolol-based treatment. Because losartan reduces serum uric acid (SUA) levels, the aim of the present study was to investigate relations of SUA with new-onset AF in the study. Methods: Hypertensive patients with electrocardiographic (ECG) left ventricular hypertrophy (LVH) and no prior AF (n = 8,243) were treated for 5.0 ± 0.4 years with losartan- or atenolol-based therapy. Associations of SUA with new-onset AF documented by Minnesota coding were assessed by Cox models using SUA and systolic blood pressure as time-varying covariates to take into account changes of SUA related to losartan or diuretic treatment, changes in renal function, and aging. Results: Time-varying SUA was associated with new AF defined by Minnesota code [hazard ratio (HR) = 1.19 per 16.8 μmol/L (1 mg/dL), (95% confidence intervals (CIs), 1.12–1.26), P < 0.0001], independent of losartan treatment [HR = 0.75 (95% CIs, 0.61–0.93), P = 0.007], older age [HR = 1.95 per 7.0 years (95% CIs, 1.73–2.20), P < 0.0001], male sex [HR = 1.46 (95% CIs, 1.09–1.94), P = 0.010] and higher Cornell voltage-duration product [HR = 1.10 per 1,023 ms·mm (95% CIs, 1.01–1.21), P = 0.034]. Similar results were obtained in Cox models with SUA levels partitioned according to baseline quartiles and in which AF was defined by physician reports or by both Minnesota coding and physician reports. Conclusions: In-treatment SUA is a strong predictor for new-onset AF in hypertensive patients, independent of effects of antihypertensive treatment, age, sex, and ECG-LVH. Further research is needed to clarify how uric acid may provoke AF (ClinicalTrials.gov identifier: NCT00338260). Original Article Thu, 17 Mar 2022 00:00:00 GMT Eran S.Zacks, Ildri M.Stokke, KristianWachtell, Darcy A.Hille, AudHøieggen, Sverre E.Kjeldsen, StevoJulius, EvaGerdts, Peter M.Okin, Richard B.Devereux, Thu, 17 Mar 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100179 https://www.explorationpub.com/Journals/em/Article/100180 Aim: The present study investigated the appearance and severity of atrial fibrillation (AF) and heart failure (HF) in 8,702 hypertensive patients with left ventricular hypertrophy (LVH) receiving antihypertensive treatment in a prospective trial. Methods: Patients who had a history of AF or HF were not included, and the participants had sinus rhythm when they were randomly allocated to blinded study medication. Endpoints were adjudicated. Results: Incident AF occurred in 679 patients (7.8%) and HF in 246 patients (2.8%) during 4.7 ± 1.1 years mean follow-up. Incident AF was associated with a > 4-fold increased risk of developing subsequent HF [hazards ratios (HRs) = 4.7; 95% confidence intervals (CIs), 3.1–7.0; P < 0.001] in multivariable Cox analyses adjusting for age, sex, race, randomized treatment, standard cardiovascular risk factors and incident myocardial infarction. The development of HF as a time-dependent variable was associated with a multivariable-adjusted 3-fold increase of the primary study endpoint (HRs = 3.11; 95% CIs, 1.52–6.39; P < 0.001) which was a composite of myocardial infarction, stroke or cardiovascular death. Incident HF was associated with a > 3-fold increased risk of developing subsequent AF (HRs = 3.3; 95% CIs, 2.3–4.9; P < 0.001). This development of AF was associated with a > 2-fold increase of the composite primary study endpoint in multivariable Cox analysis (HRs = 2.26; 95% CIs, 1.09–4.67; P = 0.028). Conclusions: Incident atrial fibrillation and heart failure are associated with increased risk of the other in treated hypertensive patients with left ventricular hypertrophy. Such high-risk hypertensive patients who subsequently develop both atrial fibrillation and heart failure have particular high risk of composite myocardial infarction, stroke or cardiovascular death (ClinicalTrials.gov identifier: NCT00338260). Original Article Thu, 24 Mar 2022 00:00:00 GMT Casper N.Bang, Anders M.Greve, LarsKøber, AnujanMuthiah, Sverre E.Kjeldsen, StevoJulius, KristianWachtell, Richard B.Devereux, Peter M.Okin, Thu, 24 Mar 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100180 https://www.explorationpub.com/Journals/em/Article/100181 Aim: Whether incident left bundle branch block (LBBB) is associated with increased cardiovascular (CV) morbidity and mortality in treated hypertensive patients with left ventricular hypertrophy (LVH) is unknown. Thus, the present study aimed to examine CV outcomes of incident LBBB in treated hypertensive patients with LVH. Methods: In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, 9,193 hypertensive patients with LVH on screening electrocardiogram (ECG) were randomized to losartan or atenolol based treatment. Participants (n = 8,567) did not have LBBB (Minnesota code 7.1) on baseline ECG. Cox regression models controlling for significant covariates assessed independent associations of incident LBBB with CV events and all-cause mortality during 4.8 years mean follow-up. Results: Annual follow-up ECGs identified 295 patients (3.4%) with incident LBBB associated with male gender (P < 0.05), older age, higher Cornell voltage (both P < 0.005) and history of diabetes, isolated systolic hypertension and prevalent CV disease. When adjusted for the history of previous CV disease, diabetes, isolated systolic hypertension, the Framingham risk score, ECG-LVH and randomized study treatment, Cox regression models showed that incident LBBB predicted higher risk of the composite endpoint CV death, myocardial infarction and stroke [hazard ratio (HR) 1.9, 95% confidence intervals (CIs) 1.3–2.9, P < 0.001], CV death (HR 3.0, 95% CIs 1.84–5.0, P < 0.001), heart failure (HR 3.6, 95% CIs 1.9–6.6, P < 0.001) and all-cause mortality (HR 3.0, 95% CIs 2.0–4.3, P < 0.001). Conclusions: These data suggest that among hypertensive patients with ECG-LVH receiving aggressive antihypertensive therapy, incident LBBB independently predicts increased risk of subsequent CV events including congestive heart failure and CV and all-cause mortality (ClinicalTrials.gov identifier: NCT00338260). Original Article Wed, 30 Mar 2022 00:00:00 GMT Casper N.Bang, ZhibinLi, Ildri M.Stokke, Sverre E.Kjeldsen, StevoJulius, Darcy A.Hille, KristianWachtell, Richard B.Devereux, Peter M.Okin, Wed, 30 Mar 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100181 https://www.explorationpub.com/Journals/em/Article/100182 Aim: While it is commonly thought that left ventricular (LV) systolic function may insidiously deteriorate in hypertensive patients, few prospective data are available to support this notion. Methods: We evaluated 680 hypertensive patients (66 ± 7 years; 45% women) with electrocardiographic (ECG)-LV hypertrophy (ECG-LVH) enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echo-sub-study free of prevalent cardiovascular disease and with baseline ejection fraction (EF) ≥ 55%. Echocardiographic examinations were performed annually for 5 years during anti-hypertensive treatment. Development of reduced systolic function was defined as incident EF < 50%. Results: During a mean follow-up of 4.8 ± 1 years, 37 patients developed reduced EF without an inter-current myocardial infarction (5.4%). In analysis of covariance, patients who developed reduced EF were more often men, had greater baseline LV diameter and LV mass, lower mean EF (all P < 0.05), and similar diastolic function indices. At the last available examination before EF reduction, independently of covariates, patients with reduced EF showed a significant increase in left atrium (LA) size, LV diameter, end-systolic stress and mitral E/A ratio, as compared to those who did not develop reduced EF (all P < 0.05). In time-varying Cox regression analysis, also controlling for baseline EF, predictors of developing reduced EF were higher in-treatment LV diameter [hazard ratio (HR) = 5.19 per cm; 95% confidence interval (CI): 2.58–10.41] and higher in-treatment mitral E/A ratio (HR = 2.37 per unit; 95% CI: 1.58–3.56; both P < 0.0001). Conclusions: In treated hypertensive patients with ECG-LVH at baseline, incident reduced EF is associated with the development of dilated LV chamber and signs of increased LV filling pressure (ClinicalTrials.gov identifier: NCT00338260). Original Article Sat, 02 Apr 2022 00:00:00 GMT MarcelloChinali, Gerard P.Aurigemma, EvaGerdts, KristianWachtell, Peter M.Okin, AnujanMuthiah, Sverre E.Kjeldsen, StevoJulius, Giovannide Simone, Richard B.Devereux, Sat, 02 Apr 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100182 https://www.explorationpub.com/Journals/em/Article/100183 Semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1 RA) molecule approved for the treatment of both type 2 diabetes (T2D) and obesity. Semaglutide has a greater impact on glycated haemoglobin (HbA1c) reduction, compared to other GLP-1 RAs, and is the first molecule of this class available in oral formulation for T2D therapy, representing a useful option for subjects and physicians less prone to start an injective drug. Interestingly, due to its remarkable effects on weight reduction, higher than other GLP-1 RAs and very close to bariatric surgery, semaglutide is designated to change the approach to obesity therapy also in the subject not affected by diabetes. In addition to these favorable features, semaglutide, similarly to other GLP-1 RAs, offers beneficial effects on cardio-vascular (CV), renal, and liver protection, making this molecule an advantageous choice in the therapeutic management of “diabesity” (coexistence of both diabetes and obesity) and its co-morbidity. Commentary Tue, 19 Apr 2022 00:00:00 GMT AgostinoMilluzzo, LuciaManuella, LauraSciacca, Tue, 19 Apr 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100183 https://www.explorationpub.com/Journals/em/Article/100184 A case of combined acute and chronic liver injury related to consumption of multi-ingredient nutritional oral supplements containing Aloe Vera gel and vitamin A among other vitamins, minerals and dietary elements such as fish and calamari oil in a 59-year-old female with unexplained hypertransaminasemia is reported. A unique complex liver injury was diagnosed on liver biopsy combining histological features of protracted acute hepatitis, mild manifestation of hypervitaminosis A and lipogranulomatous reaction attributed to Aloe Vera, vitamin A and lipids, respectively. Normalization of liver tests was achieved after discontinuation of all nutritional supplements. Updated Roussel Uclaf Causality Assessment Method (RUCAM) score (+8, probable) further supported herb-induced liver injury. The present case highlights the increasing incidence of complex histological liver injury linked to the constantly growing consumption of multi-ingredient dietary supplements and alternative medications. Case Report Sun, 24 Apr 2022 00:00:00 GMT KaterinaDelladetsima, EmanuelManesis, DinaTiniakos, StratigoulaSakellariou, Sun, 24 Apr 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100184 https://www.explorationpub.com/Journals/em/Article/100185 Cardiovascular diseases are among the leading causes of death worldwide, imposing major health threats. Reactive oxygen species (ROS) are one of the most important products from the process of redox reactions. In the onset and progression of cardiovascular diseases, ROS are believed to heavily influence homeostasis of lipids, proteins, DNA, mitochondria, and energy metabolism. As ROS production increases, the heart is damaged, leading to further production of ROS. The vicious cycle continues on as additional ROS are generated. For example, recent evidence indicated that connexin 43 (Cx43) deficiency and pyruvate kinase M2 (PKM2) activation led to a loss of protection in cardiomyocytes. In this context, a better understanding of the mechanisms behind ROS production is vital in determining effective treatment and management strategies for cardiovascular diseases. Review Wed, 27 Apr 2022 00:00:00 GMT JuanjuanFei, Laurie J.Demillard, JunRen, Wed, 27 Apr 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100185 https://www.explorationpub.com/Journals/em/Article/100186 Aim: Chronic high salt (HS) intake causes minimal changes in blood pressure (BP) but it induces augmented hypertensive response to angiotensin II (AngII) administration in rodents. The mechanism of this augmentation is not clearly understood. As tumor necrosis factor-alpha (TNF-α) induces natriuresis by activating TNF-α receptor type 1 (TNFR1) but not type 2 (TNFR2), we hypothesize that TNFR1 activity is reduced when HS is given in combination of AngII that leads to enhanced sodium retention and thus, causing augmented hypertension. The aim of this study is to examine the responses to chronic HS intake and AngII administration on the renal tissue protein expressions of TNFR1 and TNFR2 in mice. Methods: Different groups of mice (n = 6–7 in each group) chronically treated with or without AngII (25 ng/min; implanted minipump) for 4 weeks which were fed either normal salt (NS; 0.4% NaCl) or high salt (HS; 4% NaCl) diets. Systemic BP was measured by tail-cuff plethysmography. At the end of treatment period, kidneys were harvested after sacrificing the mice with euthanasia. Immuno-histochemical analysis of TNFR1 and TNFR2 proteins in renal tissues was performed by measuring the staining area and the intensity of receptors’ immunoreactivities using NIS-Elements software. The results were expressed in percent area of positive staining and the relative intensity. Results: HS intake alone did not alter mean BP (HS; 77 ± 1 vs. NS; 76 ± 3 vs. mmHg; tail-cuff plethysmography) but AngII induced increases in BP were augmented in HS group (104 ± 2 vs. 95 ± 2 mmHg; P < 0.05). The area of TNFR1 staining was higher in HS than NS group (6.0 ± 0.9% vs. 3.2 ± 0.7%; P < 0.05) but it was lower in AngII + HS than in AngII + NS group (5.0 ± 0.7% vs. 6.3 ± 0.7%; P = 0.068). TNFR2 immunoreactivity was minimal in NS and HS groups but it was high in AngII + NS and even higher in AngII + HS group. Conclusions: These data suggest that the HS induced increased TNFR1 activity that facilitates enhanced sodium excretion is compromised in elevated AngII condition leading to salt retention and augmented hypertension. Original Article Wed, 27 Apr 2022 00:00:00 GMT Dewan S. A.Majid, AlexanderCastillo, Minolfa C.Prieto, L. GabrielNavar, Wed, 27 Apr 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100186 https://www.explorationpub.com/Journals/em/Article/100187 The human body contains trillions of microbes which generally live in symbiosis with the host. The interaction of the gut microbiome with elements of the host immune system has far-reaching effects in the development of normal gut and systemic immune responses. Disturbances to this intricate relationship may be responsible for a multitude of gastrointestinal and systemic immune mediated diseases. This review describes the development of the gut microbiome and its interaction with host immune cells in both health and disease states. Review Wed, 01 Jun 2022 00:00:00 GMT TenzinChoden, Nathaniel AvivCohen, Wed, 01 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100187 https://www.explorationpub.com/Journals/em/Article/100188 Around the world, more than 6.2 million individuals have died as a result of coronavirus disease 2019 (COVID-19). According to a recent survey conducted among immunologists, epidemiologists, and virologists, this disease is expected to become endemic. This implies that the disease could have a continuous presence and/or normal frequency in the population. Pharmacological interventions to prevent infection, as well as to treat the patients at an early phase of illness to avoid hospitalization are essential additions to the vaccines. Taurine is known to inhibit the generation of all inflammatory mediators linked to the cytokine storm. It can also protect against lung injury by suppressing increased oxidants production and promoting the resolution of the inflammatory process. Neutrophil lactoferrin degranulation stimulated by taurine may have antiviral effects against SARS-CoV-2, limiting viral replication. It is hypothesized that if taurine is administered early in the onset of COVID-19 disease, it may stop the cytokine storm from progressing, lowering morbidity and mortality. Review Thu, 09 Jun 2022 00:00:00 GMT AlbertoRubio-Casillas, Ramesh C.Gupta, Elrashdy M.Redwan, Vladimir N.Uversky, RaiedBadierah, Thu, 09 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100188 https://www.explorationpub.com/Journals/em/Article/100189 Aim: Hyperuricemia as a putative risk factor for chronic kidney disease (CKD) progression remains controversial and debatable. This systematic review aims to explore the prevalence of hyperuricemia among CKD patients worldwide. Methods: This study was conducted in accordance with the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines by using the existing literature from online databases such as MEDLINE/PubMed, ScienceDirect, Google Scholar, Cochrane library and grey literature. The effect size with corresponding 95% confidence interval (CI) was calculated to assess the pooled prevalence of hyperuricemia in chronic kidney patients. The subgroup analysis based on gender and geography was also carried out by utilizing comprehensive meta-analysis, version 2.0. Results: Twenty-three studies containing 212,740 participants were eligible for quantitative synthesis. The pooled prevalence of 43.6% (35.2–52.4%) hyperuricemia was reported in patients with CKD globally. In India, 38.4% of prevalence was observed. The gender specific prevalence (9 studies) was reported as 67.4% (60.9–73.3%) in case of male patients and 32.6% (26.7–39.1%) in female patients with 95% CI. Conclusions: The prevalence of hyperuricemia was reported to be reasonably high among CKD patients worldwide. During the management of CKD, this high prevalence demands more prudent attention for this clinical complication which possibly can lead to positive renal outcomes. Meta-Analysis Thu, 23 Jun 2022 00:00:00 GMT IshfaqRashid, PoojaKatravath, PramilTiwari, SanjayD’Cruz, ShivaniJaswal, GautamSahu, Thu, 23 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100189 https://www.explorationpub.com/Journals/em/Article/100190 Chronic kidney disease (CKD) is a worldwide public health issue and has ultimately progressed to an end-stage renal disease that requires life-long dialysis or renal transplantation. However, the underlying molecular mechanism of these pathological development and progression remains to be fully understood. The human gut microbiota is made up of approximately 100 trillion microbial cells including anaerobic and aerobic species. In recent years, more and more evidence has indicated a clear association between dysbiosis of gut microbiota and CKD including immunoglobulin A (IgA) nephropathy, diabetic kidney disease, membranous nephropathy, chronic renal failure and end-stage renal disease. The current review describes gut microbial dysbiosis and metabolites in patients with CKD thus helping to understand human disease. Treatment with prebiotics, probiotics and natural products can attenuate CKD through improving dysbiosis of gut microbiota, indicating a novel intervention strategy in patients with CKD. This review also discusses therapeutic options, such as prebiotics, probiotics and natural products, for targeting dysbiosis of gut microbiota in patients to provide more specific concept-driven therapy strategy for CKD treatment. Review Thu, 23 Jun 2022 00:00:00 GMT Ying-YongZhao, Thu, 23 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100190 https://www.explorationpub.com/Journals/em/Article/100191 Not applicable. Editorial Fri, 24 Jun 2022 00:00:00 GMT GiuseppeMerra, AnnunziataCapacci, AntoninoDe Lorenzo, LauraDi Renzo, PaolaGualtieri, GiuliaFrank, MarcoMarchetti, Fri, 24 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100191 https://www.explorationpub.com/Journals/em/Article/100192 Retroelements are mobile genomic components requiring an RNA intermediate which is reverse-transcribed into complementary DNA for transposition. Human genome contains a vast amount of retroelements including retrotransposons and endogenous retroviruses. These elements are categorized according to presence or absence of long terminal repeats, LTRs or non-LTRs, as well as autonomous and non-autonomous according to involvement of reverse transcriptase. The retroelements have been accumulated in mammalian genomes over all evolutionary times through vertical transmission, and many of them were inactivated through accumulation of mutations. However, the retroelements entered into genome within the last 200,000 years are mostly functional. Some of the active retroelements are associated with varying autoimmune diseases because anti-retroelement antibodies might cross-react with other proteins in the human body. For instance, autoimmunity and inflammation could be stimulated by increased expression of long interspersed element 1 (LINE-1 or L1) or decreased L1 degradation. Different regulation of L1 expression might be related to the genetic and sex-related variations or environmental factors. Activation of retroelements is also controlled by epigenetic silencing mechanisms such as histone modification. Elevated levels of L1 retroelements could trigger the production of type I interferon, a crucial innate defense mechanism in mammals against viruses, and systemic autoimmune response is induced. Loss-of-function in some deoxyribonucleases (DNases) such as three prime repair exonuclease 1 that degrades reverse-transcribed DNA is also related to autoimmune diseases. Additionally, human endogenous retroviruses also play a role in autoimmune diseases. Involvement of retroelements in autoimmune disorders is exemplified with three diseases, i.e. systemic lupus erythematosus, Aicardi–Goutières syndrome, and multiple sclerosis. Review Fri, 24 Jun 2022 00:00:00 GMT SezerOkay, Fri, 24 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100192 https://www.explorationpub.com/Journals/em/Article/100193 Aim: The aim of this study is to propose a contrast-enhanced ultrasound (CEUS)-based morphologic classification of pyogenic liver abscess (PLA) reflecting different evolutive stages and to assess the added value of CEUS in the management of PLA. Methods: Forty-four PLAs of different etiologies in 44 patients (male/female = 24/20; mean age 66 ± 14.7 years) were evaluated with ultrasound (US) B-mode and CEUS (using SonoVue). PLAs were mainly located in the right lobe (n = 28, 63.6%) with a mean diameter of 6.8 cm [standard deviation (SD) ± 3.2, range 1.7–15 cm]. Conventional US findings were categorized as the presence and extension of liquified areas, echogenicity and echostructure of the index lesion. Peripheral hyperenhancing rim, transient segmental enhancement, hyperenhancing septa and “honeycomb” aspect were considered PLA hallmarks in the arterial phase after contrast agent injection. CEUS results were judged as clinically relevant if they modified the approach to percutaneous treatment in comparison with pre-operative US B-mode findings. Results: CEUS was superior to US B-mode as to depiction of PLA internal echostructure and enabled identification of 4 evolutive stages of PLA: type I (tumor-like), type II (“honeycomb”), type III (multiloculated with incomplete septa), and type IV (cystic-like). In 22 cases (67.4%) out of 34 who underwent percutaneous treatment, the operator tailored percutaneous approach according to PLA internal echostructure observed during CEUS exam. Conclusions: CEUS depicts the internal structure of PLA so allowing a morpho-evolutive classification of PLA and provides invaluable information for immediately tailoring the management to the single case. By showing the structure of PLA more precisely, CEUS allows a morpho-evolutive PLA classification and guides tailored management in the single case. Original Article Tue, 28 Jun 2022 00:00:00 GMT GiampieroFrancica, Tue, 28 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100193 https://www.explorationpub.com/Journals/em/Article/100194 Aim: To screen differentially expressed genes related to gastric cancer based on The Cancer Genome Atlas (TCGA) database and construct a gastric cancer diagnosis model by machine learning. Methods: Transcriptional data, genomic data, and clinical information of gastric cancer tissues and non-gastric cancer tissues were downloaded from the TCGA database, and differentially expressed genes of gastric cancer messenger RNA (mRNA) and long non-coding RNA (lncRNA) were screened out. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzed the differentially expressed genes, and the protein-protein interaction (PPI) of differentially expressed genes was constructed. Core differentially expressed genes were screened by Cytoscape software’s molecular complex detection (MCODE) plug-in. The differential genes of lncRNA were analyzed by univariate Cox regression analysis and lasso regression for further dimension reduction to obtain the core genes. The core genes were screened by machine learning to construct the gastric cancer diagnosis model. The efficiency of the gastric cancer diagnosis model was verified externally by the Gene Expression Omnibus (GEO) database. Results: Finally, 10 genes including long intergenic non-protein coding RNA 1821 (LINC01821), AL138826.1, AC022164.1, adhesion G protein-coupled receptor D1-antisense RNA 1 (ADGRD1-AS1), cyclin B1 (CCNB1), kinesin family member 11 (KIF11), Aurora kinase B (AURKB), cyclin dependent kinase 1 (CDK1), nucleolar and spindle associated protein 1 (NUSAP1), and TTK protein kinase (TTK) were screened as gastric cancer diagnostic model genes. After efficiency analysis, it was found that the random forest algorithm model had the best comprehensive evaluation, with an accuracy of 92% and an area under the curve (AUC) of 0.9722, which was more suitable for building a gastric cancer diagnosis model. The GSE54129 data set was used to verify the gastric cancer diagnosis model with an AUC of 0.904, indicating that the gastric cancer diagnosis model had high accuracy. Conclusions: Machine learning can simplify the bioinformatics analysis process and improve efficiency. The core gene discovered in this study is expected to become a gene chip for the diagnosis of gastric cancer. Original Article Thu, 30 Jun 2022 00:00:00 GMT FeiKong, ZiqinYan, NingLan, PinxiuWang, ShanlinFan, WenzhenYuan, Thu, 30 Jun 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100194 https://www.explorationpub.com/Journals/em/Article/100195 Chronic kidney disease (CKD) is a major health problem but there are many modalities to prevent and manage CKD progression. Diet is one of these factors, which needs to be evaluated more. Adenine is a water-soluble nucleoprotein that exists in both vegetables and animal foods, which triggers and aggravates fibrosis process besides other metabolic derangements such as diabetes mellitus affection that accelerates glomerular filtration rate decline rapidly. Letter to the Editor Mon, 25 Jul 2022 00:00:00 GMT MajidMalaki, Mon, 25 Jul 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100195 https://www.explorationpub.com/Journals/em/Article/100196 Aim: The etiologies, presentation, and management of downhill varices in the era of modern medicine are relatively under-explored and mostly limited to case reports or case series. Methods: Published case reports/series of patients ≥ 18 years old with proven/probable downhill esophageal varices were searched on Ovid MEDLINE and Ovid EMBASE for all published cases up to January 2021. Results: The mean age was 50.9 (standard deviation ± 17.6) years old for all downhill variceal cases. End-stage renal disease was the most common comorbidity (43.9%), followed by thyroid disease (12.2%), Behçet’s disease (9.8%), and pulmonary hypertension (7.3%). Dialysis catheters, central venous grafts, or additional catheters were additional risk factors (51.2%). Variceal bleeding presenting as hematemesis, melena, or both was the most common presenting symptom (80.5%). Conclusions: Dialysis catheter-associated superior vena cava obstruction resulted in an increased risk of downhill varices. Other causes include thyroid malignancies, pulmonary hypertension, and Behçet’s disease. Systematic Review Fri, 12 Aug 2022 00:00:00 GMT HassamAli, RahulPamarthy, Nicole LeighBolick, EslamAli, SwathiPaleti, DevikaKapuria, Fri, 12 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100196 https://www.explorationpub.com/Journals/em/Article/100197 The brain and gut are connected both physically and biochemically. The gut-brain axis includes the central nervous system, neuroendocrine and neuroimmune systems, the enteric nervous system and vagus nerve, and the gut microbiome. It can influence brain function and even behavior, suggesting that dietary interventions may help enhance and protect mental health and cognitive performance. This review focuses on the role of the microbiome and its metabolites in sleep regulation, neurodegenerative disorders, mechanisms of stress, and mood. It also provides examples of nutritional interventions which can restore healthy gut microbiota and aid with risk reduction and management of many disorders related to mental and cognitive health. Evidence suggests a shift in the gut microbiota towards a balanced composition could be a target to maintain brain health, reduce stress and improve quality of life. Review Mon, 29 Aug 2022 00:00:00 GMT MaciejChichlowski, JackCotter, NeilFawkes, NeerajPandey, Mon, 29 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100197 https://www.explorationpub.com/Journals/em/Article/100198 Aim: Psoriasis is a common chronic inflammatory skin disorder, which has adverse effects on patients’ quality of life. Natural products exhibit significant therapeutic capacities with small side effects and might be preferable alternative treatments for patients with psoriasis. This study summarizes the signaling pathways with the potential targets of natural products and their efficacy for psoriasis treatment. Methods: The literature for this article was acquired from PubMed and Web of Science, from January 2010 to December 2020. The keywords for searching included “psoriasis” and “natural product”, “herbal medicine”, “herbal therapy”, “medicinal plant”, “medicinal herb” or “pharmaceutical plant”. Results: Herbal extracts, natural compounds, and herbal prescriptions could regulate the signaling pathways to alleviate psoriasis symptoms, such as T helper 17 (Th17) differentiation, Janus kinase (JAK)/signal transducer and activator of transcription (STAT), nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and other signaling pathways, which are involved in the inflammatory response and keratinocyte hyperproliferation. The anti-psoriatic effect of natural products in clinical trials was summarized. Conclusions: Natural products exerted the anti-psoriatic effect by targeting multiple signaling pathways, providing evidence for the investigation of novel drugs. Further experimental research should be performed to screen and characterize the therapeutic targets of natural products for application in psoriasis treatment. Systematic Review Tue, 30 Aug 2022 00:00:00 GMT Ly Thi HuongNguyen, Tue, 30 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100198 https://www.explorationpub.com/Journals/em/Article/100199 Aim: Lactate dehydrogenase (LDH) is an enzyme that acts as a catalyst in the conversion of lactate to pyruvate which is abundantly found in liver, kidney, heart and muscles. Previous studies have all shown a strong positive correlation between muscle fatigue and increased serum LDH levels with type 2 diabetes mellitus but no study has actually assessed the same for prediabetes. The basic objective of this study, thus, is to find out the correlation between muscle fatigue and serum LDH levels in prediabetic individuals. Methods: A cross-sectional study was conducted in adults between 24–60 years old who were classified as prediabetic individuals as per norms established by American Diabetes Association. A total of 100 prediabetic individuals were selected for the study. Fatigability was calculated as a function of work done by the pleximeter finger of the dominant hand using Mosso’s ergograph. The study was conducted at Rajarshi Dashrath Autonomous State Medical College, Ayodhya. Results: Out of 100 prediabetic participants, 50% were males with a mean age of 44.14 ± 10.91 years and remaining 50% were females with a mean age of 41.12 ± 11.5 years. Overall, the average work done by the participants was 2.9 ± 1.2 weight lifted•total distance moved (kg•m) with an average serum LDH level of 323.84 ± 26.82 unit/litre (U/L). Conclusions: This study aimed at assessing the correlation between muscle fatigue and serum LDH levels in prediabetic individuals so that further work can be initiated to improve the quality of life in prediabetics that maybe drastically hampered due to easy fatigability in prediabetic individuals. Original Article Tue, 30 Aug 2022 00:00:00 GMT CharuMishra, VinitaAilani, DeepakSaxena, Yogesh KumarYadav, SureshSingh, VijayKumar, Ranjan KumarDixit, Tue, 30 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/100199 https://www.explorationpub.com/Journals/em/Article/1001100 Aim: Sexually transmitted diseases (STDs) need to be studied systematically to better understand their global spread. Transmission of Chlamydia trachomatis is a severe public health issue, with roughly 90 million new cases per year. Globally, Chlamydia trachomatis is the most frequent bacterial cause of STDs. Methods: To better understand the dynamics and transmission of Chlamydia, the susceptible-exposed-infected-recovered-susceptible (SEIRS) model was constructed. Using a system of nonlinear ordinary differential equations, a basic reproduction number has been calculated at an equilibrium point, and the system is locally and globally asymptotically stable at both disease-free and endemic equilibrium points. Numerical simulations illustrate the behavior and flow of Chlamydia infections in different compartments. Results: Conclude from the proposed study that 25% of individuals have been exposed to Chlamydia, of which 20% of individuals get infections due to sexual activity and 55% of individuals get recovered. Twenty percent of individuals have been exposed to Chlamydia, of which 37% of individuals have been infected due to an unhygienic environment. Of those, 43% of individuals recovered. Also, it has been found that people are more likely to get infections because of an unhygienic environment than sexually active people. The recovery rate is also much better for people who have been infected because of an unhygienic environment. Conclusions: Sexually transmitted infections can be reduced by up to 10%. While infection due to an unhygienic environment can be controlled up to a certain intensity. According to this research, public awareness campaigns and the improvement of personal hygiene will play a major role in reducing the spread of the epidemic in the future. Original Article Tue, 30 Aug 2022 00:00:00 GMT Nita H.Shah, Jalpa N.Vaghela, Purvi M.Pandya, Yash N.Shah, Tue, 30 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001100 https://www.explorationpub.com/Journals/em/Article/1001101 C1q nephropathy is a rare glomerular disease. Clinical presentation is diverse and ranges from asymptomatic hematuria or proteinuria to symptoms and signs of nephrotic/nephritic syndrome. On light microscopy, it can be classified into two subtypes: minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) group and immune complex mediated proliferative glomerulonephritis group. A case of a 19-year-old male patient presenting nausea and decreased appetite will be reported. The labs showed severe nephrotic syndrome and a progressive kidney injury over a few months that were never diagnosed. The immune workup came back negative. The patient mentioned that he was taking protein shakes a few months earlier for bettering his physical fitness. A renal biopsy was done and showed a major reduction in renal mass and C1q nephropathy. He received steroids without any improvement. He was started on hemodialysis afterward then got transplanted 8 months later. In front of this rapid deterioration, FSGS might be the underlying etiology rather than MCD. Further studies are warranted to establish a connection between protein supplements, and progression of kidney disease. Case Report Wed, 31 Aug 2022 00:00:00 GMT RandaChoueiri, JoelleFaddoul, ClaudeGhorra, Jaqueline AlNajjar, Beatrice-BlondineAkiki, SoraBoustany, VanessaNseir, Wed, 31 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001101 https://www.explorationpub.com/Journals/em/Article/1001102 Osteoporosis is a metabolic bone disorder that affects both sexes and is the most common cause of fractures. Osteoporosis therapies primarily inhibit osteoclast activity, and are seldom designed to trigger new bone growth thereby frequently causing severe systemic adverse effects. Physiologically, the intracellular redox state depends on the ratio of pro-oxidants, oxidizing agents (reactive oxygen species, ROS) and antioxidants. ROS is the key contributor to oxidative stress in osteoporosis as changes in redox state are responsible for dynamic bone remodeling and bone regeneration. Imbalances in ROS generation vs. antioxidant systems play a pivotal role in pathogenesis of osteoporosis, stimulating osteoblasts and osteocytes towards osteoclastogenesis. ROS prevents mineralization and osteogenesis, causing increased turnover of bone loss. Alternatively, antioxidants either directly or indirectly, contribute to activation of osteoblasts leading to differentiation and mineralization, thereby reducing osteoclastogenesis. Owing to the unpredictability of immune responsiveness and reported adverse effects, despite promising outcomes from drugs against oxidative stress, treatment in clinics targeting osteoclast has been limited. Nanotechnology-mediated interventions have gained remarkable superiority over other treatment modalities in regenerative medicine. Nanotherapeutic approaches exploit the antioxidant properties of nanoparticles for targeted drug delivery to trigger bone repair, by enhancing their osteogenic and anti-osteoclastogenic potentials to influence the biocompatibility, mechanical properties and osteoinductivity. Therefore, exploiting nanotherapeutics for maintaining the differentiation and proliferation of osteoblasts and osteoclasts is quintessential. Review Wed, 31 Aug 2022 00:00:00 GMT LargeeBiswas, KarishmaNiveria, Anita KamraVerma, Wed, 31 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001102 https://www.explorationpub.com/Journals/em/Article/1001103 Cardiovascular and respiratory diseases are frequently associated with transient and prolonged hypoxia, whereas hypoxia exerts pro-hypertensive effects, through stimulation of the sympathetic system and release of pressor endocrine factors. This review is focused on the role of arginine vasopressin (AVP) in dysregulation of the cardiovascular system during hypoxia associated with cardiovascular disorders. AVP is synthesized mainly in the neuroendocrine neurons of the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON), which send axons to the posterior pituitary and various regions of the central nervous system (CNS). Vasopressinergic neurons are innervated by multiple neuronal projections releasing several neurotransmitters and other regulatory molecules. AVP interacts with V1a, V1b and V2 receptors that are present in the brain and peripheral organs, including the heart, vessels, lungs, and kidneys. Release of vasopressin is intensified during hypernatremia, hypovolemia, inflammation, stress, pain, and hypoxia which frequently occur in cardiovascular patients, and blood AVP concentration is markedly elevated in cardiovascular diseases associated with hypoxemia. There is evidence that hypoxia stimulates AVP release through stimulation of chemoreceptors. It is suggested that acting in the carotid bodies, AVP may fine-tune respiratory and hemodynamic responses to hypoxia and that this effect is intensified in hypertension. There is also evidence that during hypoxia, augmentation of pro-hypertensive effects of vasopressin may result from inappropriate interaction of this hormone with other compounds regulating the cardiovascular system (catecholamines, angiotensins, natriuretic peptides, steroids, nitric oxide). In conclusion, current literature indicates that abnormal mutual interactions between hypoxia and vasopressin may significantly contribute to pathogenesis of hypertension. Review Wed, 12 Oct 2022 00:00:00 GMT EwaSzczepańska-Sadowska, TymoteuszŻera, Wed, 12 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001103 https://www.explorationpub.com/Journals/em/Article/1001104 Nutraceuticals are organic and traditional foods consumed nowadays to maintain a healthy lifestyle and get rid of lifestyle diseases like obesity, cancer, diabetes, hypertension, etc. Globally, herbal products have become increasingly popular in recent years. Wheatgrass (Triticum aestivum) is a nutraceutical proven to be a dietary supplement and beneficial for cancer-suffering patients. Wheatgrass possesses many beneficial antioxidant properties: anti-cancer activity, anti-bacterial activity, anti-fungal activity, and anti-microbial activity. Due to the presence of resistant starch, lignans, phenolic acids, alkylresorcinols, and numerous antioxidant components, including carotenoids and tocopherols, this herbal plant is deserving attention as a source of dietary fiber. Patients consume wheatgrass during cancer treatment as an adjunct to reduce toxicity associated with drugs and chemotherapy and ultimately improve long-term outcomes. Studies have proved that wheatgrass helps treat pancreatic cancer, lung cancer, and breast cancer. So, the multi-targeted herbal drug—wheatgrass—is used as an adjunct therapy alongside conventional medicine to treat cancer and other diseases. A promising therapeutic nutraceutical for avoiding lifestyle disorders is wheatgrass. Review Thu, 13 Oct 2022 00:00:00 GMT NehaMinocha, SangitaSaini, ParijatPandey, Thu, 13 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001104 https://www.explorationpub.com/Journals/em/Article/1001105 Aim: Given the male infertility’s pluri-etiological nature, thorough examinations are needed for its evaluation. Fructose and citric acid are simple biomolecules, easy to assay, which provide reliable information on the seminal vesicles and prostate, respectively. This study aimed to compare the seminal fructose and citric acid levels in men undergoing fertility evaluation and determine the relation between these markers and sperm parameters. Methods: A prospective cross-sectional study was conducted on consenting male participants. Following 2010 seminal fluid analysis (SFA) manual of World Health Organization (WHO), semen samples were analyzed for several sperm parameters, seminal fructose and citric acid. Statistical analyses were performed using IBM SPSS 24.0 software. Significant statistical difference was considered at P < 0.05. Results: There is no significant difference between seminal fructose and citric acid levels amongst men with normal and abnormal sperm parameters as median seminal fructose and citric acid levels were 11.1 (7.4–17.1) mg/mL and 11.4 (7.3–15.2) mg/mL respectively (P ≥ 0.05). However, a high level of fructose was observed in the two groups according to the reference value. The study revealed a significant positive correlation between seminal fructose levels and semen volume (coefficient rho = 0.663; P = 0.001) and between seminal citric acid levels and semen volume (coefficient rho = 0.319; P = 0.004). Conclusions: These biomarkers secretions can serve as markers of the state of their respective secreting glands and hence play a vital role in the investigation of male infertility. Original Article Thu, 27 Oct 2022 00:00:00 GMT BihTanni, Esther VoundiVoundi, AkinyinkaOmigbodun, Christopher OdianosenAimakhu, Thu, 27 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001105 https://www.explorationpub.com/Journals/em/Article/1001106 Aim: Wound healing is a complex phenomenon with various biological changes in tissue integrity, low-level laser therapy (LLLT) has acquired several unique components to help into accelerating tissue reconstruction and eventually wound healing. Thus, in the present systematic review and meta-analysis study, the role of LLLT in oral mucosal wound healing following surgical interventions was investigated. Methods: The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: “Wound Healing”, “Oral Mucosal Wound Healing”, “Laser therapy”, “Low-level laser therapy”, “Oral Surgery”, “Photobiomodulation therapy”, among 88 screened, only 12 articles were eligible for the final analysis. Results: There was a significant difference between control and laser group in all mentioned studies in the case of wound epithelialization in gingiva, with weighted mean difference (MD) of –0.28, [95% confidence interval (CI): –0.37, –0.19, P < 0.001], periodontium 1 day postoperative, with weighted MD of –0.56 (95% CI: –0.84, –0.27, P < 0.001) and 7 days postoperative, with weighted MD of –0.73 (95% CI: –0.97, –0.49, P < 0.001). In the cases of postoperative pain, LLLT has significantly declined pain in comparison with control group with weighted MD of –0.47 (95% CI: –0.69, –0.24, P < 0.001) for 7 days postoperative and –0.55 (95% CI: –0.96, –0.13, P = 0.005) 14 days postoperatively. Conclusions: LLLT can be used as a promising tool in oral surgeries because of its inevitable capability in accelerating wound healing and reducing intraoperative pain. Meta-Analysis Fri, 28 Oct 2022 00:00:00 GMT Seyyed AmirSeyyedi, SamanTaram, MohammadHeydari, RohollahValizadeh, Fri, 28 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001106 https://www.explorationpub.com/Journals/em/Article/1001107 Current evidence on benefits of night-time blood pressure (BP) lowering drug treatment on cardiovascular disease (CVD) prevention attributable to the Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy (MAPEC) trial and Bedtime hypertension treatment improves cardiovascular risk reduction (Hygia) trials has raised concern on their validity and methodology. In this commentary, the authors have updated the progress of the ongoing trials that were planned to examine the effect of night-time BP lowering drug treatment on CVD prevention. As compared to MAPEC and Hygia trials, three pragmatic trials the Blood Pressure Medication Timing (BPMedtime) trial (US), the Treatment In Morning versus Evening (TIME) trial (UK), Bedmed and Bedmed-frail (Canada) were planned without ambulatory BP monitoring. The BPMedtime trial was stopped after the pilot phase due to underestimated sample size and insufficient funds. TIME trial (UK) had a similar issue when changing the sample size from 10,269 to more than 20,000 participants. The TIME trial was completed and the initial results showing that protection against heart attack, stroke and vascular death is not affected by whether antihypertensive medications are taken in the morning or evening. The full study of the TIME trial is published in December 2022. Bedmed and Bedmed-frail trials are ongoing and will be completed in 2023. Time of taking BP lowering drug should be determined by patients at their convenience to improve the adherence. There was no difference in adverse effects of taking BP lowering drugs at night or morning. Evidence on the effect of night-time treatment on CVD events is inconsistent. The results from ongoing trials in Canada will contribute evidence to the use of BP lowering drug treatment for the prevention of CVD. Commentary Fri, 28 Oct 2022 00:00:00 GMT Chau Le BaoHo, Christopher M.Reid, Fri, 28 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001107 https://www.explorationpub.com/Journals/em/Article/1001108 Inflammatory bowel disease (IBD) is a multifactorial chronic disease. Patients with IBD have an increased risk of developing colorectal cancer which has become a major health concern. IBD might exert a role of engrams for making the condition of specific inflammation in the gut. Dysregulation of immune cells induced by the command of engrams might be crucial in the pathogenesis of damages in gut epithelium. The anti-proliferative (APRO) family of anti-proliferative proteins characterized by immediate early responsive gene-products that might be involved in the machinery of the carcinogenesis in IBD. Herein, it is suggested that some probiotics with specific bacteria could prevent the development and/or progression of the IBD related tumors. In addition, consideration regarding the application of studying APRO family proteins for the comprehension of IBD related tumors has been presented. It is hypothesized that overexpression of Tob1, a member of APRO family proteins, in the epithelium of IBD could suppress the function of adjacent cytotoxic immune cells possibly via the paracrine signaling. Perspective Fri, 28 Oct 2022 00:00:00 GMT YukaIkeda, KurumiTaniguchi, SayuriYoshikawa, HarukaSawamura, AiTsuji, SatoruMatsuda, Fri, 28 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001108 https://www.explorationpub.com/Journals/em/Article/1001109 Acquired immunodeficiency syndrome (AIDS) is a global disease caused by human immunodeficiency virus (HIV). About 50 million people have died worldwide due to HIV-1 infection alone. HIV is a primary sexually transmitted infection but can also spread via breastfeeding, blood transfer, organ transfer, etc. Early detection with the maintenance of the disease is the only way to reduce the spread and severity of the disease. There are many conventional techniques for the detection of the virus. Still, recently nano-based diagnostic method remains a little ahead of these techniques due to advancements in nanotechnology. Nanomaterial-based biosensors constitute a significant part of the discussion because of their high sensitivity and accuracy. Nanobiosensors like electronic nano biosensors, quantum dot (QD)-based biosensors, optical biosensors, electronic biosensors, electrochemiluminescence nanosensors, field-effect transistor (FET) biosensors, surface acoustic wave (SAW) biosensors, graphene-based biosensors, etc. have been widely used for detecting HIV in human blood samples. All these biosensors offer promising results in the detection of the virus. In this article, different types of nanobiosensors and their application in the field of diagnosis and maintenance of HIV was reviewed. Review Mon, 31 Oct 2022 00:00:00 GMT ShurfaMudenkattil, AgnishwarGirigoswami, ThanujashreeJayaprakash, KoyeliGirigoswami, Mon, 31 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001109 https://www.explorationpub.com/Journals/em/Article/1001110 Mitochondria are important organelles for high energy synthesis, reactive oxygen species balancing, antiapoptotic molecule production, membrane stability, intracellular calcium buffering, neuroplasticity and neurotransmission. Dysfunction in mitochondria is considered to be involved in the pathophysiology of mental problems. It has been observed that several drug types used to treat brain illnesses can harm mitochondria by altering the oxidative phosphorylation system and the gene expression of mitochondria-related proteins. In some studies, it has been observed that mitochondrial biogenesis shows a therapeutic effect in the management of mitochondrial disorders. Many therapeutic compounds are effective in the activation of mitochondrial biogenesis. The comorbidity of mental problems observed in those with mitochondrial dysfunction and the change in the efficacy of the cellular respiratory system have attracted researchers to understand the pathways and possible therapeutic strategies in neurological disorders. This article has attempted to understand the impact of mitochondrial function and mitochondrial dysfunction in the pathogenesis of brain disorders to develop potential therapeutic drugs. Review Tue, 01 Nov 2022 00:00:00 GMT MonuYadav, MiniDahiya, JyotiDagar, NarenderSingh, NidhiSharma, NitinRawat, PratibhaDhakla, NehaMinocha, AnilKumar, Tue, 01 Nov 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001110 https://www.explorationpub.com/Journals/em/Article/1001111 Fernandoa adenophylla (FA, Heterophragma adenophyllum) is a plant, cultivated throughout Africa and Southeast Asia. It contains potent phytochemicals such as novel naphthoquinones, their derivatives (peshwaraquinone, dilapachone, adenophyllone, indadone, and lapachol), and triterpenoids [ursolic acid (UA), β-sitosterol (BS), α-amyrin, and oleanolic acid (OA)] that have been assessed and reported to show potential pharmacological activities. The crude extract obtained from the plant has been investigated for certain pharmacological activities such as antibacterial, antifungal, anti-tubercular (TB), antihypertensive, and leishmanicidal activity. A novel drug delivery systems (NDDS) is the latest technique that combines innovative development, formulations, new technology, and methodologies for the safe delivery of pharmaceutical substances in the body. The present study reports the possible treatment opportunities of FA and recent possible novel drug delivery approaches for the natural medicinal phytochemicals. Review Tue, 15 Nov 2022 00:00:00 GMT Sangeet KumarMall, TejpalYadav, AafrinWaziri, Md SabirAlam, Tue, 15 Nov 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001111 https://www.explorationpub.com/Journals/em/Article/1001112 Systemic lupus erythematosus (SLE) is a chronic, immune-mediated disease associated with significant morbidity and mortality. New evidence suggests that diet, gut microbiota, intestinal permeability, and endotoxemia may modulate chronic inflammation and disease activity in SLE. This review focus on what is known about the gut microbiota in lupus mouse models and SLE patients and the possible mechanisms that connect the gut microbiota with SLE. It included 29 studies (12 animal studies, 15 human studies, and 2 included data on both), with variable results regarding alpha and beta-diversity and gut microbiota composition between lupus-mouse models and SLE patients. Ruminococcus (R.) gnavus was significantly increased in lupus nephritis (LN) in one study, but this was not corroborated by others. Despite the different results, mechanistic lupus mouse model studies have shown that gut microbiota can modulate disease activity. Interestingly, pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by a vaccine targeting the pathobiont. Moreover, studies on fecal transplants and diet on different lupus mouse models showed an effect on disease activity. In SLE patients, a higher adherence to the Mediterranean diet was associated with lower disease activity, which may be explained by the connection between diet and gut microbiota. Although gut dysbiosis has been observed in SLE patients and lupus mouse models, it remains to clarify if it is a cause or a consequence of the disease or its treatments. Further studies with larger and well-characterized populations will undoubtedly contribute to deciphering the role of gut microbiota in SLE development, progression, and outcome. Review Tue, 27 Dec 2022 00:00:00 GMT InêsAlmada-Correia, PatríciaCosta-Reis, Catarina SousaGuerreiro, João EuricoFonseca, Tue, 27 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001112 https://www.explorationpub.com/Journals/em/Article/1001113 Whipple’s disease (WD) is a rare systemic disease caused by gram-positive bacillus bacteria that invades multiple organs mainly the intestinal epithelium. Its manifestation is not only limited to the gastrointestinal tract but it also affects the joints, muscle and skin. This is a case of a 54-year-old male patient with a medical history of chronic arthritis presenting with bilateral progressive calves pain, anterior tibial hyperpigmentation, joints pain, anemia and weight loss. He was misdiagnosed as rheumatoid arthritis, for which he was treated by immunosuppressors for several years with no amelioration. After advanced investigations, he was found to have multiple retroperitoneal and mesenteric adenopathies, with an incidental finding of a mesojejunal mass during laparoscopy, from which the biopsies revealed the presence of histiocytosis and numerous intra-cytoplasmic particles with positive periodic acid–Schiff (PAS) suggesting the diagnosis of WD. Endoscopy was done and intestinal histology with polymerase chain reaction (PCR) test confirmed the diagnosis of WD. The patient was then treated with antibiotics (ceftriaxone and trimethoprim-sulfamethoxazole) with a remarkable clinical amelioration. To be aware of WD as a potential etiology behind malabsorption, musculoskeletal and skin abnormalities, is the first step in order to establish the diagnosis and provide adequate treatment, thus, improving the patient’s quality of life. WD is a rare, without antibiotic treatment deadly systemic infectious disease caused by the ubiquitary Gram-positive bacterium Tropheryma whipplei. This article aims to report a case marked with dermatomyositis like presentation that had a missed and delayed diagnosis. Case Report Wed, 28 Dec 2022 00:00:00 GMT RandaChoueiry, JoelleFaddoul, JacquelineNajjar, ClaudeGhorra, JosianeMansour, NeemtallahSafi, JosephAmara, Wed, 28 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001113 https://www.explorationpub.com/Journals/em/Article/1001114 Aim: To investigate the relationship between the incidence of contrast-induced acute kidney injury (CI-AKI) and the level of small dense low-density lipoprotein (sd-LDL) and systemic immune-inflammation index (SII) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI), and to further compare the predictive values of SII, sd-LDL and their combination for CI-AKI. Methods: A total of 674 patients were assigned to a training and a validation cohort according to their chronological sequence. The baseline characteristics of the 450 patients in the training cohort were considered as candidate univariate predictors of CI-AKI. Multivariate logistic regression was then used to identify predictors of CI-AKI and develop a prediction model. The predictive values of SII, sd-LDL and their combination for CI-AKI were also evaluated. Results: Multivariate logistic regression analysis showed that age, left ventricular ejection fraction (LVEF), sd-LDL, uric acid, estimated glomerular filtration rate (eGFR) and SII were predictors of CI-AKI. The area under the curve (AUC) of the prediction model based on the above factors was 0.846 [95% confidence interval (CI) 0.808–0.884], and the Hosmer-Lemeshow test (P = 0.587, χ2 = 6.543) proved the goodness of fit of the model. The AUC combining SII with sd-LDL to predict CI-AKI was 0.785 (95% CI 0.735–0.836), with a sensitivity of 72.8% and a specificity of 79.8%, and was statistically significant when compared with SII and sd-LDL, respectively. The predictive efficiency of combining SII with sd-LDL and SII were evaluated by improved net reclassification improvement (NRI, 0.325, P < 0.001) and integrated discrimination improvement (IDI, 0.07, P < 0.001). Conclusions: Both SII and sd-LDL can be used as predictors of CI-AKI in STEMI patients undergoing emergency PCI, and their combination can provide more useful value for early assessment of CI-AKI. Original Article Wed, 28 Dec 2022 00:00:00 GMT GuoqiShen, HaiyanHe, ZhenWang, HangQiu, YinghuaZhu, DiZheng, YangDuan, YuanLu, WenhuaLi, Wed, 28 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001114 https://www.explorationpub.com/Journals/em/Article/1001115 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can engender multi-system inflammatory syndrome. Its main symptoms are cardiovascular and thromboembolic problems that can develop into severe complications. The present case is about a 55-year-old patient who was admitted for critical ischemia of the right lower limb and necrosis of the right forefoot. The patient was infected with coronavirus disease 2019 (COVID-19) one month before her admission. The patient also has cardiovascular risks including type 2 diabetes and hypertension. The performance of ultrasounds revealed a thrombus in the right atrium and the pulmonary artery, and arteriography detected an occlusion of the right popliteal joint for which she had an endovascular recanalization and amputation of the right forefoot. This case highlights that SARS-CoV-2 infection could be considered a serious cardiovascular disease requiring cardiovascular explorations to initiate hospital management and avoid severe complications. Case Report Thu, 29 Dec 2022 00:00:00 GMT SaidMakani, AzizaLaarje, MeryemMabrouk, YounesZaid, MalakChahid, ZaynabHifdi, MeriemAzhari, ChafikElkettani, HichamBelmir, YoussefTijani, Thu, 29 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001115 https://www.explorationpub.com/Journals/em/Article/1001116 In a number of malignancies, new immuno-oncology therapies that focus on the programmed cell death 1 (PD-1) have improvised the patient condition along with a positive aftereffect. Monoclonal antibodies (mAbs) directed against PD-1 and its ligand (PD-L1), have been widely used to treat a variety of malignancies, including melanoma, renal cancer, and non-small cell lung cancer (NSCLC). Dostarlimab, a therapeutic anti-PD-1 antibody, was authorised by the United States Food and Drug Administration (FDA) in April 2021 under the trade name JEMPERLI. It is a humanised contrary PD-1 immunoglobulin G 4 (IgG4) mAb, which successfully blocks interaction with PD-L1 and PD-L2 by binding tightly to the PD-1 receptor. This article summarizes the different aspects associated with the dostarlimab, including currently available anti-PD-1/PD-L1 antibodies, pharmacokinetics (PK), pharmacodynamics, adverse reaction, and mechanism of action of dostarlimab, as well as various reported clinical trials. Graphical abstract. Role of dostarlimab in cancer Review Fri, 30 Dec 2022 00:00:00 GMT RouchanAli, Sharma ArvindVirendra, Pooja A.Chawla, Fri, 30 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001116 https://www.explorationpub.com/Journals/em/Article/1001117 In recent years, Polypodium leucotomos has emerged with a great interest for having medicinal and therapeutic potential. It is producing very promising results due to the presence of antioxidant and photoprotective properties. Electronic libraries and databases, including Scopus, PubMed, Google Scholar, Science Direct, and Web of Science were searched to identify relevant studies; 79 publications contributed to this review regarding Polypodium leucotomos botanical aspects, chemical composition, antioxidant and photoprotective activity. It is used in complementary and alternative therapies with various pharmaceutical dosage forms (systemic or topical). Thanks to the composition of phytochemical constituents present in the leaves and rhizomes which confer antioxidant and photoprotective activity that has clinical therapeutic potential to be used as systemic and topical sunscreen of natural origin for the prevention of different types of skin diseases caused by harmful ultraviolet A and ultraviolet B radiations. However, more studies are needed in the future to test the ability and enhance the capacity of sunscreen and sunblock in cosmetic formulations. To conclude, it is recommended to carry out scientific studies based on different analytical methods to evaluate the phytoconstituents potential and to develop stable pharmaceutical formulations according to the skin phototype. Review Fri, 30 Dec 2022 00:00:00 GMT Rosy Yesela Mancilla SantaCruz, Sharon VelásquezArévalo, AnasRashid, Marco Rolando AronésJara, María Segunda AuroraPrado, Fri, 30 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001117 https://www.explorationpub.com/Journals/em/Article/1001118 The aim of this review is to discuss the development of nanostructured lipid carrier (NLC) by the application of quality by design (QbD). QbD started with the evolution of the quality concept and slow adaptation of quality guidelines, which has now become a regulatory requirement. In this review, brief history and elements of QbD including risk assessment (RA) have been discussed followed by the design of experiments (DoEs) that acts as a tool to analyze the input whose variation can optimize the output with the desired goal. NLC is a versatile delivery system as researchers widely use it to administer therapeutics with different physicochemical properties. The surface of NLC can be modified, making it a suitable delivery system with targeting potential for therapeutics. Implementation of QbD provides a high-quality robust formulation that can consistently meet the patient’s requirement throughout its life cycle without compromising the safety and effectiveness of the drug and delivery system. This review discusses QbD concepts followed by the systematic development of NLC by the application of DoE. Process analytical technology (PAT) and six sigma concepts have also been included which can benefit in the development of optimized NLC. Review Sat, 31 Dec 2022 00:00:00 GMT TausifAlam, Sat, 31 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001118 https://www.explorationpub.com/Journals/em/Article/1001119 Not applicable. Letter to the Editor Thu, 16 Feb 2023 00:00:00 GMT LokmanBalyen, Thu, 16 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001119 https://www.explorationpub.com/Journals/em/Article/1001120 Aim: Extensive research is carried out throughout the world in healthy persons with obesity phenotype in concern with prevalence, metabolic profiling, etc. To the best of the authors’ knowledge, not many studies have investigated the status of adiponectin, specific inflammatory changes, oxidative damage in healthy adolescents and young adults with obesity. Present study was undertaken in adolescents and young adults of urban population in a district of North Karnataka, India, in a view to understand relationship between hormone adiponectin, oxidative stress markers like C3, C4, high sensitivity C-reactive protein (hs-CRP) in non-hypertensive, non-diabetic, euthyroid individuals with and without obesity. Methods: Participant selection was done using cluster sampling technique. Participating adolescents and young adults, each with and without obesity were included in the study. Screening of participants for diabetes, hypertension, and thyroid disorders was done, their serum level of adiponectin, hs-CRP, C3, C4, ceruloplasmin (Cp), thiobarbituric acid reactive substances (TBARS), and total antioxidant capacity (TAC) were estimated using standardized methods in National Accreditation Board for Testing and Calibration Laboratories (NABL) laboratory. Results: Adiponectin (young adults lower than adolescents, P = 0.01) levels were low, while hs-CRP and Cp (young adults higher than adolescents, P = 0.01) levels were high with increasing age in non-obese. While in persons having obesity, aging adiponectin levels were low while hs-CRP, C3, Cp levels were high significantly. Females without obesity had significantly higher values of C3 than males. Adiponectin showed higher levels in females than males, however, statistical significance could not be achieved (P = 0.308). While females with obesity, exhibited statistically lower levels of adiponectin, and higher levels of C3 and C4. Conclusions: Being non-diabetic and non-hypertensive yet obese, tagged by one time of assay, does not suffice to be categorized as healthy. Healthy young adults with obesity are exhibiting lower levels of adiponectin and higher levels of inflammatory and oxidative stress markers compared to adolescents with obesity. This implies, the so categorized “healthy obese” participants are in a phase of transition towards an unhealthy state. Original Article Wed, 22 Feb 2023 00:00:00 GMT Smita S.Sonoli, Veerappa A.Kothiwale, Reshma D.Channashetti, Wed, 22 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001120 https://www.explorationpub.com/Journals/em/Article/1001121 Aim: One single nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene has been considered a major genetic risk factor of nonalcoholic fatty liver disease (NAFLD). Data have indicated that NAFLD is related to insulin resistance and dyslipidemia, but whether rs738409 is associated with circulating lipid and lipoproteins is not fully elucidated. The main aim of this study was to assess the association of rs738409 with lipid and lipoprotein levels in patients with dyslipidemia. Methods: This was a post-hoc analysis of a study in patients with dyslipidemia recruited on an outpatient basis. Morning blood samples were collected after a 12-h fast. Genomic DNA was extracted from whole-blood samples. Results: One hundred seventy-five patients with dyslipidemia were included (97 women). Lipid levels [total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] or glycosylated hemoglobin (HbA1c) were not associated with the SNP, even after adjustment for gender, body mass index (BMI) and type 2 diabetes mellitus (T2DM), using either the additive (CC vs. CG vs. GG) or the dominant (CC vs. GG + CG) inheritance model. When data were stratified for obesity, significant associations between the variant and TC (P = 0.014) or LDL-C levels (P = 0.046) in the non-obese were observed. Pairwise comparison revealed significant changes only in TC between CC and CG genotypes (P = 0.012). Conclusions: No association was shown between rs738409 SNP and lipid/lipoprotein levels in patients with dyslipidemia. In subgroup analysis, TC was higher in non-obese, but not in obese, patients with CC, compared to CG carriers. Original Article Thu, 23 Feb 2023 00:00:00 GMT DespoinaIoannidou, Evangelia S.Makri, Stergios A.Polyzos, CharikleiaNtenti, DimitriosAgapakis, GeorgiosGermanidis, AntonisGoulas, Thu, 23 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001121 https://www.explorationpub.com/Journals/em/Article/1001122 Aim: Patients with inflammatory bowel disease (IBD) are more likely to develop anxiety or depression. The study aimed to describe the trends and disparities of suicidal ideation (SI) in hospitalized IBD patients. Methods: A retrospective study was conducted using the National Inpatient Sample (NIS) database, to analyze SI among the IBD hospitalizations from 2009 to 2019. Bivariate analysis was conducted using a chi-square test for categorical variables and an independent t-test for continuous variables. For prevalence, the trend over time was evaluated using the score test. Results: There were 1,724 IBD hospitalizations with SI for the study period. There was a male (53.8%) and white race (74.2%) predominance. The mean age was 41.47 ± 0.25 years. The hospital stay decreased for IBD hospitalizations with SI from 7.97 days in 2009 to 7.57 days in 2019 (P < 0.001). The mean hospital charge increased from $44,664 in 2009 to $66,639 in 2019 (P < 0.001). The prevalence of SIs increased from 0.17% in 2009 to 0.29% in 2019 (P < 0.001). The mean age of these hospitalizations increased from 38 years in 2009 to 42.3 years in 2019 (P = 0.02). The prevalence of generalized anxiety disorder (GAD) increased from < 1% in 2009 to 12.19% in 2019 (P < 0.001). The prevalence of depression increased from 18.04% in 2009 to 51.21% in 2019 (P < 0.001). Inpatient mortality increased from 0% in 2009 to 2.43% in 2019 (P = 0.024). Among IBD hospitalizations, the male gender had a higher association with SIs than females (odds ratio 1.32 [95% confidence interval (CI) 1.06–1.66], P = 0.014). Conclusions: There is a rise of SI among the IBD population. Specialized protocols should be in place in clinical settings and communities to identify and assess high-risk patients. Original Article Fri, 24 Feb 2023 00:00:00 GMT HassamAli, PratikPatel, RubaidDhillon, ShizaSarfraz, ShivaPoola, LuciaSmith-Martinez, KarinaFatakhova, RamonaRajapakse, Fri, 24 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001122 https://www.explorationpub.com/Journals/em/Article/1001123 Aim: Utilizing the therapeutic potentials of previously approved medications against a new target or pharmacological response is known as drug repurposing. The health and scientific communities are under continual pressure to discover new compounds with antiviral potential due to the rising reports of viral resistance and the occurrence and re-emergence of viral outbreaks. The use of antiviral peptides has emerged as an intriguing option in this search. Here, this article includes the current United States Food and Drug Administration (FDA)-approved antiviral peptides that might be enforced for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and carried out docking study of the viral protease inhibitors. Methods: In silico techniques like molecular docking was carried out using Autodock Vina software. Results: The molecular docking studies of peptide-based antiviral agents against SARS-CoV-2 [Protein Data Bank (PDB) ID: 7P35] using docking software AutoDockTools 1.5.6. Among all the docked ligands, compound velpatasvir showed interaction with residues ILE213, GLN256, LEU141, GLN189, GLU166, HIS41, CYS145, and ASN142, and displayed the highest docking score of –8.2 kcal/mol. This medication could be a novel treatment lead or candidate for treating SARS-CoV-2. Conclusions: To conclude, a docking study of peptide based antiviral compounds for their binding mode in the catalytic domain of SARS-CoV-2 receptor is reported. On molecular docking, the compounds have showed remarkable binding affinity with the amino acids of receptor chain A. The compounds occupied the same binding cavity as the reference compound maintaining the interactions with conserved amino acid residues essential for significant inhibitory potential, especially for compound velpatasvir with binding score of –8.2 kcal/mol. Graphical abstract.Affinity of viral protease inhibitors towards SARS-CoV-2 Mpro Original Article Mon, 27 Feb 2023 00:00:00 GMT AbhishekChaurasiya, AbhimannuShome, Pooja A.Chawla, Mon, 27 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001123 https://www.explorationpub.com/Journals/em/Article/1001124 Aging and age-associated diseases (AADs) are growing risk factors in societies worldwide. During aging, there is an accumulation of excessive oxygen free radicals [reactive oxygen species (ROS)] and nitrogen free radicals [reactive nitrogen species (RNS)] due to dysfunctional mitochondria, dysregulated catalytic activities of cytochrome P450 (CYP), nicotinamide adenine dinucleotide (NAD) phosphate [NADP(H)] oxidase (NOX), cyclooxygenases, and nitric oxide synthases (NOS) over the threshold of physiological levels, creating oxidative stress (OS). Excessive ROS and RNS oxidize, break, denature, and sometimes cause aggregations of key cellular components including DNA, proteins, and lipids. Normally, these denatured molecules and their aggregates are eliminated by autophagy (AP) and ubiquitin-proteosome system (UPS). However, these two proteostatic mechanisms are impaired as age progresses. As a result, these abnormal molecules turn into damage-associated molecular patterns (DAMPs), recognized as non-self by immune cells, leading to systemic chronic inflammation (SCI), which together with OS are the major causes of aging and AADs. Therefore, instead of trying to prevent and cure AADs individually, the logical approach should be the restoration of redox homeostasis by the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway which can prevent the damaging effect of OS and the upregulation of AP and UPS to eliminate DAMPs, and together they attenuate SCI to lessen the effect of inflammation. The central regulators, adenosine monophosphate-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and Sestrins, synergistically control the restoration of the redox homeostasis by activating Nrf2, the upregulation of AP-UPS, and the inhibition of SCI. The activation of these central regulators can be achieved by exercise, caloric restriction (CR), and intakes of certain CR mimetic natural compounds. Consequently, the activations of these regulators may lead to the prevention and/or attenuation of the AADs. Review Tue, 28 Feb 2023 00:00:00 GMT PrasertSobhon, GavinSavedvanich, SawaekWeerakiet, Tue, 28 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001124 https://www.explorationpub.com/Journals/em/Article/1001125 A large number of the population faces mortality as an effect of tuberculosis (TB). The line of treatment in the management of TB faces a jolt with ever-increasing multi-drug resistance (DR) cases. Further, the drugs engaged in the treatment of TB are associated with different toxicities, such as renal and hepatic toxicity. Different combinations are sought for effective anti-tuberculosis (anti-TB) effects with a decrease in toxicity. In this regard, drug repurposing has been very promising in improving the efficacy of drugs by enhancement of bioavailability and widening the safety margin. The success in drug repurposing lies in specified binding and inhibition of a particular target in the drug molecule. Different drugs have been repurposed for various ailments like cancer, Alzheimer’s disease, acquired immunodeficiency syndrome (AIDS), hair loss, etc. Repurposing in anti-TB drugs holds great potential too. The use of whole-cell screening assays and the availability of large chemical compounds for testing against Mycobacterium tuberculosis poses a challenge in this development. The target-based discovery of sites has emerged in the form of phenotypic screening as ethionamide R (EthR) and malate synthase inhibitors are similar to pharmaceuticals. In this review, the authors have thoroughly described the drug repurposing techniques on the basis of pharmacogenomics and drug metabolism, pathogen-targeted therapy, host-directed therapy, and bioinformatics approaches for the identification of drugs. Further, the significance of repurposing of drugs elaborated on large databases has been revealed. The role of genomics and network-based methods in drug repurposing has been also discussed in this article. Review Tue, 28 Feb 2023 00:00:00 GMT DilpreetSingh, AmrinderSingh, Pooja A.Chawla, Tue, 28 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001125 https://www.explorationpub.com/Journals/em/Article/1001126 Neuropathic pain (NP) remains maltreated for a wide number of patients by the currently available treatments and little research has been done in finding new drugs for treating NP. Ziconotide (PrialtTM) had been developed as the new drug, which belongs to the class of ω-conotoxin MVIIA. It inhibits N-type calcium channels. Ziconotide is under the last phase of the clinical trial, a new non-narcotic drug for the management of NP. Synthetically it has shown the similarities with ω-conotoxin MVIIA, a constituent of poison found in fish hunting snails (Conus magus). Ziconotide acts by selectively blocking neural N-type voltage-sensitized Ca2+ channels (NVSCCs). Certain herbal drugs also have been studied but no clinical result is there and the study is only limited to preclinical data. This review emphasizes the N-type calcium channel inhibitors, and their mechanisms for blocking calcium channels with their remedial prospects for treating chronic NP. Review Wed, 01 Mar 2023 00:00:00 GMT ShikhaChoudhary, RaminderjitKaur, AafrinWaziri, ArunGarg, RenuKadian, Md SabirAlam, Wed, 01 Mar 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001126 https://www.explorationpub.com/Journals/em/Article/1001127 m6A RNA methylation, a predominant type of RNA modification, is involved in regulating mRNA splicing, stability, and translation as well as the interaction between nucleoproteins and noncoding RNAs. Recent studies have revealed that m6A RNA methylation plays a critical role in the self-to-non-self-recognition of immune cells against endogenous mutations in cancer and exogenous organism-related infections. As an epigenetic mechanism, m6A RNA modification induces immune cell signal transduction, which is altered in the tumor microenvironment, as detected in liquid biopsy. Furthermore, m6A RNA methylation-related inflammation is involved in the cellular response to viral infections, including the emerging severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Given the importance of the immune response in maintaining homeostasis in higher eukaryotes, m6A RNA methylation could be useful not only for the early detection of cancer but also for SARS-CoV-2 screening during a global pandemic. Commentary Wed, 01 Mar 2023 00:00:00 GMT HiromichiSato, TomoakiHara, ChihiroOtsuka, YasukoArao, YoshikoTsuji, YumikoHamano, MireiOgita, Ericdi Luccio, TakaakiHirotsu, AndreaVecchione, HideshiIshii, Wed, 01 Mar 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001127 https://www.explorationpub.com/Journals/em/Article/1001128 Aim: Hypertension (HTN) is a major cause of heart failure but the precise pathways by which HTN leads to heart failure are not resolved. Newer echocardiographic techniques permit assessment of myocardial contraction in different orientations defining left ventricular (LV) shortening as percentage longitudinal, circumferential and radial strain. Methods: A systematic search was conducted of Medline and Embase. The search was conducted from the inception of each database on June 30, 2022. Search terms “left ventricular strain” or speckle tracking AND heart failure with preserved ejection fraction or diastolic dysfunction AND HTN. Results: Six studies were identified and subject to detailed review. LV ejection fraction (LVEF) was not significantly different in patients with heart failure with preserved ejection fraction (HFpEF) and HTN compared to individuals with or without HTN. Global longitudinal strain (GLS) and global circumferential strain (GCS) were significantly (P < 0.0001) different (lower) in patients with HFpEF and HTN compared to patients with HTN without HFpEF and control individuals without HTN or other conditions. In contrast, global radial strain (GRS) was not significantly (P < 0.054) different in patients with HFpEF and HTN compared to individuals without HTN or other conditions. GRS was significantly (P < 0.01) different in individuals with HFpEF and HTN compared to individuals with HTN. Conclusions: Assessment of LV strain is an important advance in the assessment of LV function in patients with HTN and HFpEF as it identifies patients with reduced LV strain while there was no difference in LVEF. GLS and GCS provide the best separation between patients with HFpEF and HTN compared to individuals with HTN without HFpEF. This study advances the possibility of redefining the classification of heart function and heart failure for patients with HTN by either classifying patients mainly by LV strain or sub-classifying patients with HTN and HFpEF by LV strain. Meta-Analysis Mon, 10 Apr 2023 00:00:00 GMT Simon W.Rabkin, Mon, 10 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001128 https://www.explorationpub.com/Journals/em/Article/1001129 Oxygen free radicals [reactive oxygen species (ROS)] and nitrogen free radicals [reactive nitrogen species (RNS)] are generated by mitochondria during adenosine triphosphate synthesis, and catalytic activities of cytochrome P450, nicotinamide adenine dinucleotide phosphate oxidases (NOXs), cyclooxygenases, and nitric oxide synthases during drug catabolism, phagocytosis, and acute inflammation. Under normal circumstances, low levels of ROS and RNS provide redox signalings that control many essential physiological processes. As age progresses ROS and RNS increase excessively due to dysfunctional mitochondria, dysregulated NOX, and other free-radical generating sources, leading to oxidative stress, which causes oxidation and denaturation of key cellular components including DNA, proteins, and lipids, which become abnormal, constituting damage-associated molecular pattern (DAMP), recognized as ‘non-self’ by immune cells, leading to inflammation which is mediated by nuclear factor kappa B-inflammasome, p38-c-Jun N-terminal kinase and Janus kinase-signal transducer and activator of transcription pathways. DAMPs are continuously released from damaged and senescent cells, causing an otherwise normally transient inflammation turning into systemic chronic inflammation, the root cause of aging and age-associated diseases (AADs). Cells restore redox balance by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway that induces the synthesis and release of antioxidation molecules and enzymes including haem oxygenase-1, which also inhibits the three inflammatory pathways. Furthermore, upregulation of autophagy (AP) can get rid of abnormal molecules, prevent the generation of DAMPs, and attenuate inflammation. Both AP and Nrf2 signalings decrease with age. The upregulations of Nrf2, AP, and downregulation of inflammation are controlled by sensors of energy and stress levels, i.e., adenosine monophosphate-activated protein kinase, silent information regulator 1, and Sestrins, as well as the extracellular matrix, while mammalian targets for rapamycin complex 1, a nutrient sensor, act in the opposite direction. If the balance of these sensor systems becomes dysregulated, aging process accelerates, and the risk of AADs increases. Review Tue, 18 Apr 2023 00:00:00 GMT PrasertSobhon, GavinSavedvanich, SawaekWeerakiet, Tue, 18 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001129 https://www.explorationpub.com/Journals/em/Article/1001130 The gastrointestinal (GI) microbiome remains an emerging topic of study and the characterization and impact on human health and disease continue to be an area of great interest. Similarly, the coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the healthcare system with active disease, lasting effects, and complications with the full impact yet to be determined. The most current evidence of the interaction between COVID-19 and the GI microbiome is reviewed, with a focus on key mediators and the microbiome changes associated with acute disease and post-acute COVID-19 syndrome (PACS). Review Wed, 26 Apr 2023 00:00:00 GMT Kevin V.Houston, AnkitPatel, MichaelSaadeh, AlejandraVargas, Ana RosaVilela Sangay, Steve M.D’Souza, Byung SooYoo, David A.Johnson, Wed, 26 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001130 https://www.explorationpub.com/Journals/em/Article/1001134 Aim: Forward head posture (FHP) is a very common pathological neck posture among people who frequently use multimedia devices, and it could be related to some musculoskeletal disorders. However, its role in influencing lung function and its relationship with neck disability are still debated in the literature. Therefore, the aim of the present study was to investigate the influence of FHP on respiratory function, and to explore a possible relationship between FHP and neck discomfort. Methods: A cross-sectional study was conducted on a sample of 83 subjects (35.7 ± 8.4 years aged), enrolled at the Ferrari corporate wellness program “Formula Benessere”. Craniovertebral angle (CVA) was measured with a digital goniometer to assess head posture: FHP was defined with a CVA < 50° in an upright position. Spirometry was conducted according to European Respiratory Society/American Thoracic Society (ERS/ATS) criteria. Finally, subjects enrolled were evaluated through a self-administered neck disability index (NDI) questionnaire. Results: Among the 60 participants with agreement about the CVA measurements, 45 had FHP (11 females and 34 males) with lower CVA values. No significant differences were found in spirometric parameters between subjects with FHP (n = 45) and subjects without FHP (n = 15). Furthermore, the two groups did not differ either in NDI scores (P = 0.148). Conclusions: There is no clear relationship between FHP and respiratory function indices. Moreover, no differences have been found in NDI values between subjects with FHP and subjects without FHP. Respiratory rehabilitation strategies should be focused on other parameters than FHP itself. Original Article Wed, 26 Apr 2023 00:00:00 GMT GiadaAnnarumma, AlessandroSpinelli, AlessandroSerio, TammaroDi Fraia, Carlo MariaGallinoro, LucreziaCaoduro, DomizianoTarantino, AndreaDemeco, EricaKeeling, StefanoPalermi, AlessandroBiffi, FeliceSirico, Wed, 26 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001134 https://www.explorationpub.com/Journals/em/Article/1001131 DNA paralogs that have a length of at least 1 kilobase (kb) and are duplicated with a sequence identity of over 90% are classified as low copy repeats (LCRs) or segmental duplications (SDs). They constitute 6.6% of the genome and are clustering in specific genomic loci. Due to the high sequence homology between these duplicated regions, they can misalign during meiosis resulting in non-allelic homologous recombination (NAHR) and leading to structural variation such as deletions, duplications, inversions, and translocations. When such rearrangements result in a clinical phenotype, they are categorized as a genomic disorder. The presence of multiple copies of larger genomic segments offers opportunities for evolution. First, the creation of new genes in the human lineage will lead to human-specific traits and adaptation. Second, LCR variation between human populations can give rise to phenotypic variability. Hence, the rearrangement predisposition associated with LCRs should be interpreted in the context of the evolutionary advantages. Review Wed, 26 Apr 2023 00:00:00 GMT LisanneVervoort, Joris R.Vermeesch, Wed, 26 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001131 https://www.explorationpub.com/Journals/em/Article/1001132 Aim: The main objective of the study was to formulate, evaluate and perform an optimization study of chaulmoogra oil-loaded solid lipid nanoparticles (SLNs) based gel. Methods: The study involves isolation, identification, and quantification of hydnocarpic acid (HA), using high-performance thin-layer chromatography (HPTLC) and characterization using ultraviolet (UV), nuclear magnetic resonance (NMR), and mass spectroscopy (MS), and differential scanning calorimetry (DSC). Different concentration of assorted solid lipids and surfactants was used for the preparation of SLN gel with the improved transdermal application. Size distribution, entrapping efficiency, transmission electron microscopy (TEM), and percent yield were tested for the prepared SLN and the characterization of SLN gel was evaluated on the basis of in vitro diffusion study, stability studies, homogeneity, and skin irritancy test. Results: The amount of HA quantified in the oil sample was found to be 54.84% w/w. The percent yield and entrapment efficiency (EE) of HA SLNs were 96.176 ± 1.338% and 90.2 ± 0.5% respectively. The in vitro percent cumulative drug release was 80.89% for the developed SLN, the homogeneity test showed no grittiness, and the prepared gel was found to be effective as it shows no signs of erythema post-treatment of 10 days. The in vitro dissolution studies showed better results for SLN gel when compared to SLN suspension. Conclusions: The nano-gel could be a better option for the topical delivery of herbal drugs with improved bioavailability providing several benefits over conventional formulation. Original Article Wed, 26 Apr 2023 00:00:00 GMT RabeaParveen, MonalishaSamal, Nafis, Hayat M.Mukhtar, SayeedAhmad, Wed, 26 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001132 https://www.explorationpub.com/Journals/em/Article/1001133 The novel coronavirus disease-2019 (COVID-19) has created a major public health crisis. Various dietary factors may enhance immunological activity against COVID-19 and serve as a method to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The dietary factors that are responsible for boosting immunity may provide a therapeutic advantage in patients with COVID-19. Investigators have demonstrated that vitamins B6, B12, C, D, E, and K, and trace elements like zinc, copper, selenium, and iron may serve as important tools for immunomodulation. Herein this is a review the peer-reviewed literature pertaining to dietary immunomodulation strategies against COVID-19. This review is intended to better define the evidence that dietary modifications and supplementation could positively influence the proinflammatory state in patients with COVID-19 and improve clinical outcomes. With appropriate insight, therapeutic interventions are discussed and directed to potentially modulate host immunity to mitigate the disease mechanisms of COVID-19. Review Wed, 26 Apr 2023 00:00:00 GMT Lindsey B.Cundra, ManasaVallabhaneni, MichaelSaadeh, Kevin V.Houston, Byung SooYoo, SteveD’Souza, David A.Johnson, Wed, 26 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001133 https://www.explorationpub.com/Journals/em/Article/1001135 The periodontium is an appropriate target for regeneration, as it cannot restore its function following disease. Significantly, the periodontium’s limited regenerative capacity could be enhanced through the development of novel biomaterials and therapeutic approaches. Notably, the regenerative potential of the periodontium depends not only on its tissue-specific architecture and function but also on its ability to reconstruct distinct tissues and tissue interfaces, implying that the development of tissue engineering techniques can offer new perspectives for the organized reconstruction of soft and hard periodontal tissues. With their biocompatible structure and one-of-a-kind stimulus-responsive property, hydrogels have been utilized as an excellent drug delivery system for the treatment of several oral diseases. Furthermore, bioceramics and three-dimensional (3D) printed scaffolds are also appropriate scaffolding materials for the regeneration of periodontal tissue, bone, and cartilage. This work aims to examine and update material-based, biologically active cues and the deployment of breakthrough bio-fabrication technologies to regenerate the numerous tissues that comprise the periodontium for clinical and scientific applications. Review Wed, 26 Apr 2023 00:00:00 GMT SimonaSantonocito, SalvatoreFerlito, AlessandroPolizzi, VincenzoRonsivalle, GiuseppeReitano, AntoninoLo Giudice, GaetanoIsola, Wed, 26 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001135 https://www.explorationpub.com/Journals/em/Article/1001136 Aim: Childhood obesity is accompanied by an increased prevalence of abnormal glucose tolerance (AGT) including the prediabetes states. This study aims to investigate and evaluate the use of oral glucose tolerance test (OGTT) for detecting AGT among overweight and obese children. Methods: A retrospective study was conducted on 895 overweight and obese Chinese children (6–18 years) with obesity assessment and analysis of demographic, anthropometric, and biochemical parameters data between January 2006 and December 2015 at Tseung Kwan O Hospital, Hong Kong Special Administrative Region. Results: The proportion of males and older age group was 63.7% and 55.9%, respectively. Girls were more in older age groups (62.7% vs. 52.0%, P = 0.002). AGT occurred in 17.1% of the cohort [impaired glucose tolerance (IGT) was the most frequent morbidity (11.3%)]. After regression analysis, female sex, low-density lipoprotein (LDL), triglyceride (TG), older age group, and homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 4.1 were significantly associated with AGT. Conclusions: AGT is common in overweight and obese Chinese children. Girls, older age, higher LDL, TG and HOMA-IR ≥ 4.1 showed significant association with AGT. OGTT is essential and fit-for-purpose to detect AGT in overweight and obese children. Original Article Wed, 26 Apr 2023 00:00:00 GMT Vivian Yuet HoLaw, Jack Hong MingYoung, Hak YungNg, Louis Tsz WangChan, Wed, 26 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001136 https://www.explorationpub.com/Journals/em/Article/1001137 Aim: To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patients hospitalized with mild coronavirus disease 2019 (COVID-19) and contrast them with patients with identical clinical conditions but treated with high doses of vitamin D (vitD). Methods: From the 218 patients recruited (ClinicalTrials.gov NCT04411446), 16 participated in this sub-study and were randomized to a single oral dose of 500,000 IU vitD (n = 10) or placebo (n = 6). Plasmatic Ang II and Ang-(1-7) levels were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8, and 10 and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay before and after treatment. Parallel, serum 25-hydroxyvitamin D3 (25-OH vitD) concentrations as vitD status was measured by a chemiluminescence immunoassay. Results: A trend towards an increase in Ang-(1-7) and a decrease in Ang II levels were observed in placebo- and vitD-treated COVID-19 patients compared to baseline values. There was no difference in Ang II and Ang-(1-7) levels between placebo- and vitD-treated COVID-19 patients. Similar results were obtained with ILs profile. COVID-19 patients showed an increase in the protective component of the RAS which was not improved by vitD treatment. Conclusions: VitD did not improve RAS disbalance in COVID-19. Notwithstanding, the authors visualize that acute treatment with high doses of vitD may show a trend to a decline in inflammatory ILs and an increase in protective markers. Finally, the authors would like to highlight the limitations of this preliminary study, namely the small number of patients and the use of a large single bolus dose of vitD rather than lower daily doses for extended periods with prolonged follow-up times. All these factors need special consideration in the designs of new vitD supplementation trials. All these factors need special consideration in the designs of new vitD supplementation trials (ClinicalTrials.gov identifier: NCT04411446). Original Article Wed, 26 Apr 2023 00:00:00 GMT Mauro G.Silva, FelipeInserra, JavierMariani, LauraAntonietti, MyriamNuñez, CarlosTajer, LeónFerder, Pablo I. F.Inserra, FernandoRoss, MilagroSánchez Cunto, MagalíBertelli, Gabrielade Larrañaga, Eliana M.Cela, Daniel H.González Maglio, Mariela M.Gironacci, WalterManucha, Wed, 26 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001137 https://www.explorationpub.com/Journals/em/Article/1001138 Aim: Given the myriad of negative sequalae associated with cancer and its treatment, the palliative use of cannabis by cancer patients is increasingly of special interest. This research sought to explore associations of acute and sustained use of legal market edible cannabis products on pain, cognition, and quality of life in a group of cancer patients. Methods: In this observational study, cancer patients completed a baseline appointment, a two-week ad libitum cannabis use period, and an acute administration appointment that included assessments before cannabis use, one-hour post-use, and two-hour post-use. Participants completed self-report questionnaires related to the primary outcomes and the Stroop task as a measure of objective cognitive function. Results: Twenty-five participants [mean (standard deviation, SD) age = 54.3 years (15.6); 13 females (52.0%)] completed all study appointments and were included in the analysis. Sustained cannabis use was associated with improvements in pain intensity, pain interference, sleep quality, subjective cognitive function, and reaction times in the Stroop task, but no change in general quality of life was observed. High levels of cannabidiol (CBD) use during the two-week ad libitum use period was associated with steeper improvements in pain intensity and sleep quality. Participants reported improvements in pain intensity and increased feelings of subjective high after acute use. High levels of Δ9-tetrahydrocannabinol (THC) use during the acute administration appointment was associated with steeper increases in feelings of subjective high. Improvements in pain were associated with improvements in subjective cognitive function. Conclusions: This observational study is among the first of its kind to examine associations between legal market, palliative cannabis use, and subjective and objective outcomes among cancer patients. These early findings concerning pain intensity, sleep quality, and cognitive function can help to inform future, fully powered studies of this important topic (ClinicalTrials.gov identifier: NCT03617692). Original Article Thu, 27 Apr 2023 00:00:00 GMT GregoryGiordano, RenéeMartin-Willett, Laurel P.Gibson, D. RossCamidge, Daniel W.Bowles, Kent E.Hutchison, Angela D.Bryan, Thu, 27 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001138 https://www.explorationpub.com/Journals/em/Article/1001139 Aim: To investigate the causal impact of diet and sedentary behavior on Brazilian schoolchildren’s overweight/obesity using the data from observational studies. Methods: Annual cross-sectional nutritional surveys over the 2013–2015 period, with 26,712 children old 7–12 years in Florianópolis, Brazil, provided the data for this analysis. The surveys applied an online previous-day recall questionnaire on food intake and physical/sedentary activities. Outcome measures were overweight/obesity, whereas exposure variables were daily frequencies of consuming sugary drinks and ultra-processed foods, the total number of dietary items consumed and the total number of sedentary activities per day, and consuming breakfast, mid-morning snacks, lunch, afternoon snack, dinner, and evening snack. Control variables included child age, sex, family income, school shift, survey year, day of the week the questionnaire refers to, metabolic equivalents (METs) of physical activities (PAs), and the quality of dietary and PA reports. Causal effects were estimated by augmented inverse probability weighting. Results: Daily consumption of sugary drinks, eating ten or more foods, and engaging in three or more sedentary behaviors per day significantly increased the odds ratios (ORs) of being overweight/obese in the range of 3–24% compared to the reference, with 95% confidence intervals in the range of 1–32%. Among 19 ORs with P-value ≤ 0.05, only 3 exceeded 10%. Conclusions: Under certain conditions, not uncommon in large-scale monitoring and surveillance studies, it is possible to evaluate the causal effects of diet and sedentary activities on overweight/obesity. Daily consumption of sugar-sweetened beverages, eating ten or more foods, skipping breakfast, and engaging in three or more sedentary behaviors per day significantly increased the odds of being overweight/obese. Original Article Thu, 27 Apr 2023 00:00:00 GMT EmilKupek, Thu, 27 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001139 https://www.explorationpub.com/Journals/em/Article/1001140 Aim: Polycystic ovarian syndrome (PCOS) is the most common endocrine condition, affecting 5–7% of reproductive-age women worldwide. It is associated with low-grade chronic inflammation, insulin resistance, and metabolic syndrome. Studies have shown ceruloplasmin (Cp) as an independent risk factor for metabolic syndrome and magnesium (Mg), which is required for proper glucose utilization. This study aimed to compare the serum Mg and Cp in PCOS and healthy women and correlate their levels with changes in biochemical, hormonal, and gynaecological aspects of PCOS. Methods: The study comprised 98 women diagnosed with PCOS using the Rotterdam criteria and 75 age-matched healthy control subjects. The level of serum Cp and Mg were determined using Somani Ambade colorimetric method and methylthymol blue method respectively. Results: Serum Cp was higher and Mg levels were lower significantly in PCOS patients in comparison with controls. Mg was inversely correlated with fasting blood glucose and directly correlated with follicle-stimulating hormone (FSH). Cp was inversely correlated with prolactin and thyroid-stimulating hormone. Multiple regression analysis revealed that Cp correlates with both the level of luteinizing hormone (LH) and LH/FSH ratio, whereas serum Mg did not have a significant correlation with any of the clinical variables. Logistic regression analysis revealed elevated Cp, antral follicle count (AFC), body mass index (BMI), weight, and irregular menses increase the risk of developing PCOS, whereas Mg was not a risk factor. However, high LH and LH/FSH ratios were risk factors for hypomagnesemia. In conclusion, serum Cp levels in PCOS may be evaluated as an additional risk factor in association with AFC, BMI, weight, and irregular menses. Conclusions: Mg deficiency and high Cp play an important etiological role in PCOS pathogenesis. Thus, research evaluating dietary interventions and supplementation is warranted. Original Article Fri, 28 Apr 2023 00:00:00 GMT PratibhaMisra, RahulGopinath, NikitaNaredi, Sibin MadathanKandi, ShyamRaj, YaongamphiVashum, Fri, 28 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001140 https://www.explorationpub.com/Journals/em/Article/1001142 Aim: There is a correlation between the number of resected lymph nodes (LNs) and survival as well as staging in patients with colorectal cancer (CRC). This cohort discussed the effect of the number of dissected LNs on the prognosis [survival, disease-free survival (DFS)] of patients with stage II and III CRC. Methods: In this historical prospective cohort study, the records of 946 patients with CRC operated in the Seyyed-Al-Shohada hospital in Isfahan from 1998 to 2014 were enrolled. Then the impact of LNs on the overall survival (OS) and DFS were analyzed. Results: The number of removed LNs was higher among males [mean difference = 1.38, t (944) = 2.232, P-value = 0.02]. The median of the DFS for the patients with 1 to 20 LN removal was 104 months [95% confidence interval (CI): 90.97–117.03], while this number for the patients with more than 20 nodes was 166 months (95% CI: 140.41–191.58). DFS between two groups of CRCs, LN removal 1–20, and greater than 20. Age and number of LN removal were significant predictors of the DFS. There was a strong and statistically significant correlation between DFS and OS among CRC patients. Conclusions: This study shows that if the number of resected LNs in patients with CRC is more than 20, it will increase in DFS and OS. Original Article Tue, 30 May 2023 00:00:00 GMT Reihane MokarianRajabi, Fariborz MokarianRajabi, ElhamMoazam, SanaMohseni, MohammadTarbiat, AnahitaEmami, AmirNik, Sayyideh ForoughHosseini, Tue, 30 May 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001142 https://www.explorationpub.com/Journals/em/Article/1001141 Aim: In patients with cancer, ischemic heart disease, and peripheral vascular disease, the neutrophil-lymphocyte ratio (NLR), a measure of systemic inflammation, has been demonstrated to predict mortality. This study aimed to evaluate the inflammatory status, and also examine the impact of NLR on renal outcomes (mortality and composite endpoints) in non-dialysis chronic kidney disease (CKD) patients. Methods: This prospective cohort was conducted at a tertiary care public teaching hospital. The NLR greater than 3.53 was taken as an indication of systemic inflammation. The outcome measures include composite endpoints (end-stage renal disease, dialysis commencement, doubling serum creatinine from the baseline), and mortality. Kaplan-Meier plots and a multivariate Cox proportional hazard model were employed to analyze the outcomes. Results: A cohort of 360 patients aged 53.7 years ± 13.9 years had a median follow-up of 14 months ± 4.24 months and was evaluated for inflammatory status and renal outcomes. The proportion of inflammation was found to be 101 (28.7%). Higher NLR levels had shown an increased incidence of mortality (5.3%) and composite endpoints (12.3%). In reference to the NLR quartile (Q1), the highest quartile (Q4) had shown 3 times increased hazards for mortality and 95.0% increased risk of hazards for composite endpoints Q4 hazard ratio (HR) 3.09; 95% confidence interval (CI) 1.38–6.91 (P = 0.006), and Q4 HR 1.93; 95% CI 1.22–3.08 (P = 0.005), respectively. Higher NLR was positively associated with urea, creatinine, alkaline phosphatase, Pt-Global web tool©/Patient-Generated Subjective Global Assessment score and negatively correlated with estimated glomerular filtration rate, albumin, hemoglobin. Conclusions: NLR is a potential predictor of mortality and composite endpoints in CKD patients even before they undergo dialysis. Additionally, inflammation should be regarded as a common comorbid condition in CKD patients due to its high prevalence. Original Article Wed, 17 May 2023 00:00:00 GMT IshfaqRashid, PramilTiwari, SanjayD’Cruz, ShivaniJaswal, Wed, 17 May 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001141 https://www.explorationpub.com/Journals/em/Article/1001143 Aim: Being overweight and obesity are factors in the negative modification of bronchial asthma (BA). The mechanisms of the aggravating effect of obesity on the course of BA have not yet been fully determined, but include changes in external respiration. The aim of the study was to study the effect of being overweight/obesity on spirometric parameters and on the occurrence of dysanapsis in children and adolescents with BA. Methods: It was a cross-sectional, open, single-center study. The data were obtained from 428 patients with atopic BA aged 7 years to 17 years, 12.0 [9.0; 14.0], and 72.9% (312/428) of them were boys. The children were divided into 3 groups: group 1—normal body weight; group 2—overweight; and group 3—obesity. All participants underwent spirometry, the ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) was calculated and the diagnosis of dysanapsis was performed. Results: As body weight increases, a progressive decrease in FEV1/FVC is revealed—group 1: 79.55% [71.37; 85.43]; group 2: 76.82% [70.12; 82.03]; and group 3: 76.28% [67.04; 79.89] P = 0.004; as well as a decrease in Z FEV1/FVC: group 1—1.23 [–2.18; –0.28]; group 2—1.54 [–2.19; –0.68]; and group 3—1.75 [–2.63; –0.90] P = 0.02. Dysanapsis was detected in 37.7% (159/428) of patients. The incidence of dysanapsis increased statistically significantly with increasing body mass index (BMI) and amounted to: with normal body weight—31.7% (77/243), with overweight—42.0% (55/131), and with obesity—50% (27/54) P = 0.016. Conclusions: In children and adolescents with BA, as BMI increases, there is a statistically significant decrease in the ratio of FEV1/FVC, and, consequently, bronchial patency; the incidence of dysanapsis also increases statistically significantly. Taken together, this indicates the formation of an obstructive pattern of external respiration under the influence of being overweight and obesity in children and adolescents with BA. Original Article Wed, 31 May 2023 00:00:00 GMT Regina N.Khramova, Tatyana I.Eliseeva, Elena V.Tush, D.Yu.Ovsyannikov, Vilya A.Bulgakova, Georgii S.Ignatov, Lamara A.Oganyan, Olga V.Khaletskaya, Wed, 31 May 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001143 https://www.explorationpub.com/Journals/em/Article/1001144 In the context of in-hospital care management, the need for infusion therapies involves the choice of appropriate devices. Historically, there is no consensus about the preference for vascular accesses, although the data present in the literature would seem to favor peripheral ones due to fearful complications and a non-negligible rate of bloodstream infections. It is also true the decision for central routes is sometimes dictated by the patient’s general clinical conditions (especially as a result of surgery) or by the need to establish continuous short or long-term support therapies. Therefore, it would seem anachronistic to favor one strategy rather than another. Probably data should be reviewed, considering and evaluating the correct application of indications and guidelines for both positioning and management of venous accesses, without facing methodological biases that could lead to scarcy and inconclusive results; although it is undeniable that some conditions promote the onset of complications. Letter to the Editor Thu, 01 Jun 2023 00:00:00 GMT ReginaFrontera, MirkoBarone, Thu, 01 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001144 https://www.explorationpub.com/Journals/em/Article/1001146 Aim: Pseudoneurological complaints (PNCs) are highly prevalent among the general population. Coronavirus disease 2019 (COVID-19) adversely influences such complaints in individuals who recovered from COVID-19. This study determined the prevalence and identified the predictors of PNCs among individuals who had previously experienced COVID-19 and their healthy counterparts. Methods: This case-control study analyzed the data of 878 Bangladeshi adults (439 patients). Laboratory-confirmed COVID-19 individuals were considered cases, and the controls were those who never tested positive for COVID-19. The controls were matched with cases’ sex and age. The seven-item pseudoneurological sub-scale of the subjective health complaints scale produced by Eriksen et al. evaluated PNCs. The descriptive analysis estimated the prevalence of PNCs among the subgroups, whereas multiple logistic regression models were used to determine the predictors of PNCs. Results: Overall, the prevalence of PNCs was 40%; however, patients who recovered from COVID-19 reported a PNC rate of 67.4%. The regression analysis identified COVID-19 as a robust independent predictor of PNCs. Furthermore, occupation, monthly household income, current living location, hypertension, and recovery period from acute COVID-19 were independently associated with PNCs. Conclusions: This study revealed a significant association between COVID-19 and PNCs. The results of this study will be helpful when discussing, planning, and implementing strategies to alleviate the overburden of PNCs among COVID-19 survivors. Original Article Wed, 28 Jun 2023 00:00:00 GMT MohammadAli, Atia SharminBonna, TajnuvaMehjabin, Wed, 28 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001146 https://www.explorationpub.com/Journals/em/Article/1001145 Aim: Cardiovascular diseases (CVD) are the leading cause of death globally. In the condition of type 2 diabetes mellitus (T2DM), the prevalence of CVD increase parallel with the rise of metabolic complication and higher incidence of coronary artery stenosis. The aim of this study was to compare the level of percent stenosis in coronary arteries in patients with coronary artery disease (CAD) with and without T2DM, and to measure the severity of CVD using Gensini score (GS) through angiographic data. Methods: The current study was conducted in tertiary care specialized hospital in Delhi, India. The level of percent stenosis in coronary arteries was compared in patients with CAD with and without T2DM. The patients were divided into two groups: group I included 100 patients with T2DM, and group II included 100 non-diabetic CAD patients who underwent coronary angiography by Judkin’s technique. The severity of CVD was measured by GS through angiographic data. The serum levels of glycated haemoglobin (HbA1c) ≥ 6.5% were considered diabetic. Results: Significant difference was observed in serum HbA1c, and random blood sugar levels between group I and group II were also observed (P ≤ 0.001). Serum HbA1c shows a significant positive association with GS (r = 0.36, P = 0.007). Conclusions: The study shows a significant level of stenosis in coronary arteries of CAD diabetic patients. However, further prospective analysis of a larger population size will be needed to strengthen the findings and the significant association. Original Article Wed, 28 Jun 2023 00:00:00 GMT DharmsheelShrivastav, Pradeep KumarDabla, Desh DeepakSingh, VimalMehta, Wed, 28 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001145 https://www.explorationpub.com/Journals/em/Article/1001147 Gastrointestinal (GI) cancer is one of the leading causes of death that affect many patients around the world. The coronavirus disease 2019 (COVID-19) pandemic significantly impacted our healthcare system in large that diagnosis and management of GI cancer have suffered with a reduction in cancer screening. This review will describe the current practices of cancer screening during COVID-19 pandemic and summarize how each GI cancer (esophageal, gastric, colorectal, and hepatocellular cancers) has been affected by COVID-19. World widely there has been a decreasing trend in screening, diagnosis, and management of GI cancers during the COVID-19 pandemic. Many healthcare institutions are now observing the effect of this change and implementing practice variations to adapt to the pandemic. Review Wed, 28 Jun 2023 00:00:00 GMT Byung SooYoo, AnkitPatel, Kevin V.Houston, AlejandraVargas, Ana RosaVilela Sangay, Steve M.D’Souza, David A.Johnson, Wed, 28 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001147 https://www.explorationpub.com/Journals/em/Article/1001148 Aim: Among treatments for chronic non-cancer pain (CNCP), cannabinoid-based medicines (CBMs) have become extremely popular. Evidence remains modest and limited primarily to delta-9-tetrahydrocannabinol (THC) for neuropathic pain; nevertheless, the use of various CBMs, including cannabidiol (CBD) to treat neuropathic, nociceptive, and mixed pain has increased globally. This observational case-series assessed the impact of CBMs as a complementary treatment by pain mechanism and cannabinoid profile over three months. Methods: An analysis of patients with CNCP and treated with CBMs who consented to an ongoing registry was performed. Outcomes were patient-reported such as the Edmonton Symptom Assessment System-Revised, Brief Pain Inventory-Short Form, and 36-Item Short Form Health Survey. Data from patients with complete outcomes for baseline and 3-month follow-up was extracted. Characteristics of adverse drug reactions (ADRs), including a description of the suspected product were also assessed. Results: A total of 495 patients were part of this analysis (mean age = 56 years old; 67% women). At 3-month, the proportional use of THC:CBD balanced and THC-dominant products increased. Patients with neuropathic pain had higher pain-severity scores vs. nociceptive pain. In addition to patients with neuropathic pain, patients with nociceptive and mixed pain also reported improvements in pain severity and secondary symptoms such as anxiety, depression, drowsiness, fatigue, sleep disturbances, and overall, health-related quality of life. THC-dominant treatment is more likely to be recommended when pain is severe, whereas CBD-dominant is favored for less severe cases. ADRs were more frequent among cannabis-naive patients and included dizziness, headache, and somnolence among others. Conclusions: Findings suggest that CBMs can be effective for neuropathic as well as nociceptive and mixed pain. THC is more frequently recommended for neuropathic and severe pain. Future research on CBMs in pain management must include details of CBM composition, and pain mechanism and must consider potential ADRs. Original Article Fri, 30 Jun 2023 00:00:00 GMT LucileRapin, Maria FernandaArboleda, ErinProsk, CharlesSun, AlainWatier, MichaelDworkind, Fri, 30 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001148 https://www.explorationpub.com/Journals/em/Article/1001149 Enhanced recovery after surgery (ERAS) is a recommended surgical strategy at present, the core content is to reduce perioperative stress response and postoperative complications through perioperative multi-mode analgesia and intensive surgery. Electroacupuncture (EA) has been widely used in various clinical applications, and its efficacy and safety have been fully proven. The application of acupuncture in ERAS will have an important impact on rehabilitation research and development. In this review, the molecular mechanism of EA in ERAS are summed up from promoting perioperative efficacy to improving postoperative immune status. The combination of EA and ERAS may better promote the recovery of patients and the development of rehabilitation. Review Fri, 30 Jun 2023 00:00:00 GMT YuMao, LifangYang, Fri, 30 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001149 https://www.explorationpub.com/Journals/em/Article/1001150 Aim: Traumatic brain injury (TBI) is a common neurological condition, which can present with a wide range of neuropsychological symptoms. Treating this broad spectrum of symptoms represents a significant medical challenge. In part because of this, there is growing interest in the use of medical cannabis to treat the sequelae of TBI, as medical cannabis has been used to treat multiple associated conditions, such as pain. However, medical cannabis represents a heterogeneous collection of therapies, and relatively little is known about their effectiveness in treating TBI symptoms. The aim of the present study was therefore to assess medical cannabis use in patients with TBI. Methods: In the present study, a retrospective chart review was conducted of patterns of cannabis use and TBI symptoms in individuals who used medical cannabis to treat TBI-related symptoms. All subjects were recruited from a medical cannabis clinic, where cannabis was authorized by physicians, using licensed cannabis products. A total of 53 subjects provided written consent to have their charts reviewed. Results: Neuropsychiatric conditions, including depression, pain, and anxiety were frequent in this group. The most common forms of medical cannabis consumption at intake included smoking, vaping, and oral ingestion. Patients used a combination of high tetrahydrocannabinol (THC)/low cannabidiol (CBD) and low THC/high CBD products, typically 1–3 times per day. Medical cannabis appeared to be relatively well-tolerated in subjects, with few serious side effects. At follow-up, subjects self-reported improvements in TBI symptoms, although these were not statistically significant when assessed using validated questionnaires. Conclusions: Overall findings indicate modest potential benefits of medical cannabis for TBI, but further research will be required to validate these results. Original Article Fri, 30 Jun 2023 00:00:00 GMT Elizabeth N. R.Schjelderup, Caroline A.MacCallum, Lindsay A.Lo, JessieDhillon, AprilChristiansen, CarlyPistawka, KathrynRintoul, William J.Panenka, Alasdair M.Barr, Fri, 30 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001150 https://www.explorationpub.com/Journals/em/Article/1001151 Aim: There is a strong comorbidity between methamphetamine (MA) and alcohol use whereby MA use may contribute to increased alcohol consumption. This study aims to determine the associations between alcohol drinking and MA-associated behaviors among MA users in relation to mood disorders, suicidal ideation, and health-related quality of life (HR-QoL). Methods: Substance use characteristics were obtained in 106 participants with MA use at a substance abuse treatment center by using the Severity of Dependence Scale (SDS) and the Thai version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). Current alcohol drinking behaviors were estimated using the Substance Outcomes Profile (SOP), which was developed and translated from the Treatment Outcomes Profile, by computing the number of alcohol units x days per month of alcohol use. The Mini-International Neuropsychiatric Interview (M.I.N.I.) was used to estimate lifetime histories of mood disorders and substance abuse and current suicidal ideation. Results: Current suicidal ideation in MA users is to a large extent predicted by the severity of current alcohol and MA use, female gender, and a lifetime history of mood disorders (major depression, dysthymia, and hypo-mania). Moreover, a lifetime history of mood disorders is positively associated with the severity of MA, but not with alcohol use. Partial least squares (PLS) path modeling shows that lowered HR-QoL in MA users is predicted by the SDS score and alcohol dosing (both inversely) and that lifetime diagnoses of mood disorders and MA use (both inversely) and alcohol dependence (positively) have significant effects on HR-QoL which are completely mediated via the SDS score. Conclusions: In MA users, the severity of dependence, and MA and/or alcohol use exert adverse effects on current suicidal ideation and HR-QoL. Mechanistic explanations are given which may explain the inverse associations between the severity of MA and alcohol use in MA abusers. Original Article Fri, 30 Jun 2023 00:00:00 GMT KetsuparJirakran, MichaelMaes, NapakkawatBuathong, RasmonKalayasiri, Fri, 30 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001151 https://www.explorationpub.com/Journals/em/Article/1001152 Bochdalek hernia (BH) is a congenital diaphragmatic defect primarily diagnosed in neonates and is usually left-sided. Adult diagnosis, especially of right-sided BH is exceedingly rare and usually presents with symptoms. Till now, only 31 cases have been diagnosed to be right-sided BH along with intrathoracic kidney. This report presents a 26-year-old asymptomatic male who was incidentally diagnosed with a massive right congenital diaphragmatic hernia. Imaging revealed severe abdominal herniation, a right intrathoracic ectopic kidney, and a right liver lobe hypoplasty along with hypertrophied left liver lobe extending down to the pelvic cavity. Several surgeons were consulted, with controversial opinions on whether elective surgery should be performed or withheld. Due to the high risk associated with surgery and the patient’s choice, the surgery was deferred. For almost 18 months, the patient did not report any symptoms or complications. This case highlights the rarity of asymptomatic right-sided BH in adults and the challenges in determining a management approach. Also, it proposes a conservative approach for such patients as a management modality. Most extensive diagrammatic defect reported is estimated to have a neck defect of 10 cm. Most BH cases have been treated surgically and reports on the outcome of a conservative approach are exceedingly rare. In such cases, patient preferences and a thorough risk assessment play vital roles in decision-making regarding conservative versus surgical approaches. Case Report Thu, 13 Jul 2023 00:00:00 GMT HusamEl Sharu, ZaidAlwarawrah, MohammadAlqaisieh, AhmedHebishy, Thu, 13 Jul 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001152 https://www.explorationpub.com/Journals/em/Article/1001153 Aim: Many small datasets of significant value exist in the medical space that are being underutilized. Due to the heterogeneity of complex disorders found in oncology, systems capable of discovering patient subpopulations while elucidating etiologies are of great value as they can indicate leads for innovative drug discovery and development. Methods: Two small non-small cell lung cancer (NSCLC) datasets (GSE18842 and GSE10245) consisting of 58 samples of adenocarcinoma (ADC) and 45 samples of squamous cell carcinoma (SCC) were used in a machine intelligence framework to identify genetic biomarkers differentiating these two subtypes. Utilizing a set of standard machine learning (ML) methods, subpopulations of ADC and SCC were uncovered while simultaneously extracting which genes, in combination, were significantly involved in defining the subpopulations. A previously described interactive hypothesis-generating method designed to work with ML methods was employed to provide an alternative way of extracting the most important combination of variables to construct a new data set. Results: Several genes were uncovered that were previously implicated by other methods. This framework accurately discovered known subpopulations, such as genetic drivers associated with differing levels of aggressiveness within the SCC and ADC subtypes. Furthermore, phyosphatidylinositol glycan anchor biosynthesis, class X (PIGX) was a novel gene implicated in this study that warrants further investigation due to its role in breast cancer proliferation. Conclusions: The ability to learn from small datasets was highlighted and revealed well-established properties of NSCLC. This showcases the utility of ML techniques to reveal potential genes of interest, even from small datasets, shedding light on novel driving factors behind subpopulations of patients. Original Article Wed, 26 Jul 2023 00:00:00 GMT MosesCook, BessiQorri, AmruthBaskar, JalalZiauddin, LucaPani, ShashibushanYenkanchi, JosephGeraci, Wed, 26 Jul 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001153 https://www.explorationpub.com/Journals/em/Article/1001308 Breath analysis is a relatively new topic of study that has a lot of potential for both therapeutic and scientific applications. The volatile organic compounds (VOCs) found in breath are created internally by the body due to environmental interactions, gut and air passage bacteria, and metabolites of ingested precursors. Breath analysis may help diagnose disorders linked to changes in breath composition, according to several recent research. An analytical technique that shows promise for the metabolic examination of breath is infrared spectroscopy. Chemical substances found in exhaled human breath can be used to diagnose illnesses, determine physiological states, or evaluate environmental exposure. Exhaled breath (EB) is the perfect biological fluid because it is nearly limitless and causes little to no discomfort for the patient, which promotes collaboration. Furthermore, EB can be sampled without requiring medical professionals or privacy, and it usually doesn’t produce infectious waste (despite airborne infections), which makes breath analysis a desirable method for a variety of applications. Breath analysis is a non-invasive method that solely uses the volatile composition of the EB to characterize the bloodstream and airways’ volatile content, which indicates the state and condition of the entire body’s metabolism. The absorption strength of the metabolites is still very modest, though, because EB contains minimal amounts of them. Several of the most recent uses of infrared spectroscopy for breath analysis, published between 2020 and 2024, are presented in this study. Review Thu, 17 Apr 2025 00:00:00 GMT Andrei A.Bunaciu, Hassan Y.Aboul-Enein, Thu, 17 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001308 https://www.explorationpub.com/Journals/em/Article/1001154 Aim: Cigarette smoking is an addictive behavior that requires high motivation to change, a phenotype related to the functional activity of the brain. The study aims to examine motivation to change among cigarette smokers and to study the association between functional brain activity and motivation to change smoking behaviors. Methods: Motivation to change smoking behaviors of 107 current smokers receiving services in a university hospital was obtained using the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). Brain activities related to motivation to change were also explored in a subgroup using functional magnetic resonance imaging (fMRI). Results: The results showed that most of the current smokers (n = 68, 63.6%) were low motivated to change despite receiving health-related services. Brain activities in the left of the temporal, frontal gyrus, and superior medial gyrus of smokers with motivation were greater activated than those without. In contrast, the brain activities in the left precentral gyrus and bilateral paracentral lobules of smokers without motivation were greater activated. Conclusions: These preliminary results show the differences in brain activities between smokers with and without motivation to change and warrant further research to see if motivated smokers can quit smoking using a series of strategies based on their functional activities of the brain. Original Article Thu, 31 Aug 2023 00:00:00 GMT RasmonKalayasiri, SakolSrisuklorm, AttapongChatdon, WitayaSungkarat, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001154 https://www.explorationpub.com/Journals/em/Article/1001159 The idea that proteins are the main determining factors in the functioning of cells and organisms, and their dysfunctions are the first cause of pathologies, has been predominant in biology and biomedicine until recently. This protein-centered view was too simplistic and failed to explain the physiological and pathological complexity of the cell. About 80% of the human genome is dynamically and pervasively transcribed, mostly as non-protein-coding RNAs (ncRNAs), which competitively interact with each other and with coding RNAs generating a complex RNA network regulating RNA processing, stability, and translation and, accordingly, fine-tuning the gene expression of the cells. Qualitative and quantitative dysregulations of RNA-RNA interaction networks are strongly involved in the onset and progression of many pathologies, including cancers and degenerative diseases. This review will summarize the RNA species involved in the competitive endogenous RNA network, their mechanisms of action, and involvement in pathological phenotypes. Moreover, it will give an overview of the most advanced experimental and computational methods to dissect and rebuild RNA networks. Review Thu, 31 Aug 2023 00:00:00 GMT CristinaBarbagallo, MicheleStella, CarmenFerrara, AngelaCaponnetto, RosaliaBattaglia, DavideBarbagallo, CinziaDi Pietro, MarcoRagusa, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001159 https://www.explorationpub.com/Journals/em/Article/1001160 Abnormal energy metabolism is one of the ten hallmarks of tumors, and tumor cell metabolism provides energy and a suitable microenvironment for tumorigenesis and metastasis. Tumor cells can consume large amounts of glucose and produce large amounts of lactate through glycolysis even in the presence of oxygen, a process called aerobic glycolysis, also known as the Warburg effect. Lactate is the end product of the aerobic glycolysis. Lactate dehydrogenase A (LDHA), which is highly expressed in cancer cells, promotes lactate production and transports lactate to the tumor microenvironment and is taken up by surrounding stromal cells under the action of monocarboxylate transporter 1/4 (MCT1/4), which in turn influences the immune response and enhances the invasion and metastasis of cancer cells. Therapeutic strategies targeting lactate metabolism have been intensively investigated, focusing on its metastasis-promoting properties and various target inhibitors; AZD3965, an MCT1 inhibitor, has entered phase I clinical trials, and the LDHA inhibitor N-hydroxyindole (NHI) has shown cancer therapeutic activity in pre-clinical studies. Interventions targeting lactate metabolism are emerging as a promising option for cancer therapy, with chemotherapy or radiotherapy combined with lactate-metabolism-targeted drugs adding to the effectiveness of cancer treatment. Based on current research, this article outlines the role of lactate metabolism in tumor metastasis and the potential value of inhibitors targeting lactate metabolism in cancer therapy. Review Thu, 31 Aug 2023 00:00:00 GMT WeimeiXing, XiaoweiLi, YuliZhou, MengsenLi, MingyueZhu, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001160 https://www.explorationpub.com/Journals/em/Article/1001155 Aim: The use of 5-fluorouracil in glaucoma surgery is associated with a high risk of corneal complications, as even minimal doses of the drug at the ocular surface inhibit corneal epithelial cell division and lead to corneal epitheliopathy and erosion. The aim of this study was to evaluate the clinical and functional results of the proposed method of postoperative adjuvant subconjunctival injection of 5-fluorouracil after non-penetrating deep sclerectomy (NPDS) in comparison with the control group. Methods: Patients with primary open-angle glaucoma who underwent NPDS and received at least 1 subconjunctival injection of 5-fluorouracil in the postoperative period were included in a two-group retrospective comparative study. Patients who received a subconjunctival injection of 5-fluorouracil after surgery using the standard technique were included in Group 1; Group 2 included patients who received an injection using the proposed method. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), rate of corneal complications, and number of office visits during the first 4 weeks after surgery were analysed. Results: The compared groups did not differ in demographic characteristics, preoperative BCVA, and IOP parameters. Fluorescein-stained corneal epithelial defects were statistically significantly more frequent in Group 1 compared to Group 2, P < 0.001. Four weeks post NPDS IOP reduction was greater in Group 2, P = 0.042. Mean BCVA loss was 1.9 lines in Group 1 and 1.3 lines in Group 2, P < 0.001. The number of follow-up visits during the first month after surgery was lower in Group 2 than in Group 1, P = 0.002. Conclusions: The proposed method was simple and effective in reducing the risk of corneal epithelial defects after subconjunctival injection of 5-fluorouracil, significantly improving clinical and functional outcomes of NPDS and reducing the need for outpatient visits. Original Article Thu, 31 Aug 2023 00:00:00 GMT Sergey N.Svetozarskiy, Andrey N.Andreev, Alexander V.Shvaikin, Svetlana V.Scherbakova, Anna N.Sporysheva, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001155 https://www.explorationpub.com/Journals/em/Article/1001157 Stroke, a central nervous system (CNS) injury, is responsible for the second leading cause of death in the world, bringing a great burden on the world. Stroke is normally divided into ischemic and hemorrhagic stroke, among which ischemic stroke takes up 87% proportion. Accumulating evidence has denoted a rather pivotal role for autophagy in the pathogenesis of ischemic stroke, which is activated in neuronal cells, glial cells, and endothelial cells. Besides, circular RNAs (circRNAs), a novel type of epigenetic regulation, are highly expressed in the CNS and are involved in the process of CNS diseases, which is regarded as an important molecular mechanism in ischemic stroke. Meanwhile, circRNA and autophagy have a significant correlation. The intracellular signaling pathways regulating autophagy can either restrain or activate autophagy. However, under the circumstances of ischemic stroke, the precise communication between circRNA and stroke is largely unknown. This review aims to provide a summary of the relationship between circRNA, autophagy, and ischemic stroke, as well as the current research advancements in understanding how circRNA regulates autophagy in the context of stroke. Review Thu, 31 Aug 2023 00:00:00 GMT YitingHong, LiyuanGu, BingHan, HonghongYao, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001157 https://www.explorationpub.com/Journals/em/Article/1001156 Broncho-alveolar lavage (BAL) represents a safe tool for the differential diagnosis of various pulmonary fibrotic diseases. Idiopathic pulmonary fibrosis (IPF) belongs to a heterogeneous group of diseases, interstitial lung disease (ILD), presenting a progressive impairment of pulmonary functions. IPF is characterized by the excessive accumulation of extracellular matrix (ECM) in the alveolar parenchyma that may lead to irreversible pulmonary remodeling. Although the exact pathogenetic mechanisms leading to IPF development are still unclear it has been demonstrated that fibroblasts differentiating toward myofibroblasts are the major actors involved in this process. The possibility of obtaining and expanding fibroblasts from the BAL of ILD patients for research purposes has been recently explored. This approach is discussed here as a reliable chance, helpful to advance the scientific community knowledge and to devise two- and three-dimensional (2D/3D) pre-clinical in vitro models of these diseases, further overcoming technical and ethical concerns related to the use of fibroblasts derived from tissue biopsy. Perspective Thu, 31 Aug 2023 00:00:00 GMT PaoloGiannoni, EmanuelaBarisione, MarcoGrosso, Danielade Totero, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001156 https://www.explorationpub.com/Journals/em/Article/1001158 Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can result in a range of persistent symptoms impacting everyday functioning for a considerable proportion of patients, a condition termed Long coronavirus disease (COVID) or post COVID-19 syndrome. The severity and set of symptoms vary between patients, and include fatigue, cognitive dysfunction, sleep disturbances, palpitations, tachycardia, pain, depression, and anxiety. The high prevalence of Long COVID combined with the lack of treatment approaches has resulted in considerable unmet clinical needs. There is a growing body of evidence that cannabis-based medicinal products (CBMPs) can be used to treat symptoms including pain, anxiety, depression, fatigue, sleep, headaches, and cognitive dysfunction, which are commonly reported in Long COVID. This article provides an overview of the pathophysiology of Long COVID and discusses preliminary pre-clinical, clinical trials, and real-world evidence (RWE) for CBMPs in the context of Long COVID. This review summarises current clinical trials and studies exploring CBMPs in Long COVID. The current evidence provides a rationale to further explore CBMPs as a treatment for Long COVID symptoms. In addition to further randomised controlled trials (RCTs), the increasing availability of CBMPs globally, coupled with the continued prevalence of Long COVID in the population, also highlights the value of real-world data in the research of CBMPs in Long COVID. Critically, there is an evident need for multidisciplinary approaches of CBMPs and Long COVID in real-world clinical practice settings. Review Thu, 31 Aug 2023 00:00:00 GMT HannahThurgur, Anne KatrinSchlag, ElizabethIveson, AdeleHosseini, MichaelLynskey, David J.Nutt, Thu, 31 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001158 https://www.explorationpub.com/Journals/em/Article/1001164 Aim: Childhood obesity is a global health concern that affects the daily life of children. It has a complex pathogenesis that involves genetic and nutritional factors among others. Moreover, the dysbiosis of gut microbiota has been recently associated with the development and progression of obesity. Methods: A total of 43 faecal samples were collected from Saudi children; among them, 26 were normal and 17 were obese. Whole genomic DNA was extracted from their faecal samples and sequenced using an Illumina Sequencing platform. Results: The gut microbiota was dominated by Phyla Firmicutes (69.00%) and Bacteroidetes (20.00%), followed by Actinobacteria (8.50%). In children with obesity, the abundance of Firmicutes was decreased, while Bacteroidetes was relatively enriched. Verrucomicrobia and Proteobacteria were not detected in the obese group, but they were found in low abundance in the control group. Phylum Firmicutes was dominated by the families Ruminococcaceae (17.86%) and Lachnospiraceae (41.20%). Less Ruminococcaceae was found in the obese group. Phylum Bacteroidetes was dominated by families Bacteroidaceae (12.98%) and Prevotellaceae (4.10%), which were enriched in the obese group. Genus Blautia (14.29%) was highly abundant, followed by Bacteroides (12.98%), Faecalibacterium (10.08%), Bifidobacterium (7.96%), and Prevotella (5.04%). Ruminococcus_g2 and _g4, Subdoligranulum, Roseburia, Fusicatenibacter, Anaerostipes, and Faecalibacterium were decreased (P > 0.05) in the obese group, while Streptococcus, Agathobacter, Prevotella, Bacteroides, and Bifidobacterium were increased (P > 0.05). Conclusions: In conclusion, a diverse bacterial community was profiled in Saudi preschool children, and changes in bacterial community composition were observed between obese- and normal-weight children. Original Article Mon, 04 Sep 2023 00:00:00 GMT Shymaa M.Al-Jabri, Effat A.Al-Judaibi, Yasser A.Al-Gamdee, Awatif A.Al-Judaibi, Mon, 04 Sep 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001164 https://www.explorationpub.com/Journals/em/Article/1001161 The development of patient-specific prosthetics, medication administration, the manufacture of tissues and organs, and surgical planning have all benefited significantly from the use of three-dimensional (3D) printing during the past few decades. The enthusiasm for customized healthcare has increased because the United States of America launched its Precision Medicine Initiative in 2015. In a nutshell, the phrase “personalized medicine” refers to medical care that is tailored to the patient. Nevertheless, the biomedical materials utilized in 3D printing are often stable and can’t react or be adaptive and intelligent in the body’s interior environment. Ex-situ fabrication of these substances, which includes printing on a flat substrate before releasing it onto the target surface, may cause a discrepancy between the printed portion and the target areas. The 3D printing is one method that might be used to provide customized treatment. The four-dimensional (4D) printing is developed while employing components that can be tweaked with stimulation. Several researchers have been looking at a new area recently that blends medicines with 3D and 4D printing. The development of 4D printing overcomes a number of these issues and creates a promising future for the biomedical industry. Smart materials that have been pre-programmed can be used in 4D printing to create structures that react interactively to outside stimuli. Despite these benefits, dynamic materials created using 4D technology remain in their development. As a result, several ideas for pharmaceutical products and formulas that may be customized and printed have emerged. Furthermore, Spritam®, the first medicine produced by 3D printing, has indeed reached a medical facility. This paper offers a summary of several 3D and 4D printing technologies and how they are used in the pharmaceutical industry for customized medicine and drug delivery systems. Review Fri, 01 Sep 2023 00:00:00 GMT PankajSharma, VinayJain, Fri, 01 Sep 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001161 https://www.explorationpub.com/Journals/em/Article/1001162 The current literature findings on autophagy’s beneficial and detrimental roles in diabetes mellitus (DM) and diabetes-related comorbidities were reviewed. The effects of oral hypoglycaemic medicines and autophagy in DM. Autophagy plays an important function in cellular homeostasis by promoting cell survival or initiating cell death in physiological settings was also assessed. Although autophagy protects insulin-target tissues, organelle failure caused by autophagy malfunction influences DM and other metabolic diseases. Endoplasmic reticulum and oxidative stress enhance autophagy levels, making it easier to regulate stress-induced intracellular changes. Evidence suggests that autophagy-caused cell death can occur when autophagy is overstimulated and constitutively activated, which might prevent or develop DM. Even though the precise role of autophagy in DM complications is uncertain, deregulation of the autophagic machinery is strongly linked to beta cell destruction and the aetiology of DM. Thus, improving autophagy dysfunction is a possible therapeutic objective in treating DM and other metabolic disorders. Review Fri, 01 Sep 2023 00:00:00 GMT MilanObradovic, SonjaZafirovic, ZoranGluvic, JelenaRadovanovic, Esma R.Isenovic, Fri, 01 Sep 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001162 https://www.explorationpub.com/Journals/em/Article/1001163 Wound healing is a very dynamic and complex process as it involves the patient, wound-level parameters, as well as biological, environmental, and socioeconomic factors. Its process includes hemostasis, inflammation, proliferation, and remodeling. Evaluation of wound components such as angiogenesis, inflammation, restoration of connective tissue matrix, wound contraction, remodeling, and re-epithelization would detail the healing process. Understanding key mechanisms in the healing process is critical to wound research. Elucidating its healing complexity would enable control and optimize the processes for achieving faster healing, preventing wound complications, and undesired outcomes such as infection, periwound dermatitis and edema, hematomas, dehiscence, maceration, or scarring. Wound assessment is an essential step for selecting an appropriate treatment and evaluating the wound healing process. The use of artificial intelligence (AI) as advanced computer-assisted methods is promising for gaining insights into wound assessment and healing. As AI-based approaches have been explored for various applications in wound care and research, this paper provides an overview of recent studies exploring the application of AI and its technical developments and suitability for accurate wound assessment and prediction of wound healing. Several studies have been done across the globe, especially in North America, Europe, Oceania, and Asia. The results of these studies have shown that AI-based approaches are promising for wound assessment and prediction of wound healing. However, there are still some limitations and challenges that need to be addressed. This paper also discusses the challenges and limitations of AI-based approaches for wound assessment and prediction of wound healing. The paper concludes with a discussion of future research directions and recommendations for the use of AI-based approaches for wound assessment and prediction of wound healing. Review Fri, 01 Sep 2023 00:00:00 GMT Dinh T. P.Le, Tuan D.Pham, Fri, 01 Sep 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001163 https://www.explorationpub.com/Journals/em/Article/1001165 Aim: The purpose of this study was to examine the association among body mass, blood pressure (BP), and cognitive functioning for octogenarians and centenarians. Methods: A total of 300 participants (221 centenarians and 79 octogenarians) from the Georgia Centenarian Study were included in this study. Demographic variables included age, gender, and ethnicity. Body mass was measured with the body mass index (BMI), and systolic and diastolic BP, as well as mean arterial pressure (MAP) and the Mini-Mental Status Examination (MMSE) were assessed. Results: Results showed age differences indicating that centenarians had lower BMI and MMSE scores when compared to octogenarians. Women had lower cognitive functioning scores compared to men. Black Americans had higher BMI and BP as well as lower MMSE scores. Participants with low BMI values (< 18.5 kg/m2) and normal BP had a significantly lower MMSE score when compared to those with elevated BMI values (≥ 25 kg/m2 to < 30 kg/m2) and high BP. Multiple regression analyses determined that age, gender, ethnicity, and BMI were significantly associated with cognitive function in very late life. Conclusions: The results suggest that extreme values of body mass (low and high) in combination with normal BP (< 130 mmHg) are potential risk factors for compromised cognition. Original Article Fri, 15 Sep 2023 00:00:00 GMT PeterMartin, RotemArieli, MaiKabayama, KayoGodai, YasuyukiGondo, Mary AnnJohnson, Leonard W.Poon, Fri, 15 Sep 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001165 https://www.explorationpub.com/Journals/em/Article/1001166 Complex enzyme interactions play a role in the spread of cancer, a process fueled by unregulated cell proliferation. DNA topoisomerases, which are important for fixing DNA topological problems, have drawn a lot of interest as potential targets for anti-cancer medications. Cancer treatment, which includes radiation, surgery, and chemotherapy, tries to control cell survival, demise, and mobility, which are mediated by ion transportation across cell membranes via channels and carriers. The malignant transition is characterised by altered channels and carriers. Chemoresistance, which commonly develops after chemotherapy, denotes decreased therapeutic effectiveness against cancer progression. Chemosensitizers are used in combination with anti-cancer medications to overcome this resistance, particularly against adenosine triphosphate (ATP)-binding cassette (ABC) transporters including P-glycoprotein, multidrug resistance-associated protein 1 (MRP1), breast cancer resistance protein (BCRP). Effective targets for treatment are transcription factors, which play a key role in the development of cancer. With the use of interactions with receptors, enzymes, ion channels, transporters, and TFs, nanotechnology improves the safety of tumour localization, treatment, and diagnostics. As a result of mutations or altered signalling, rat sarcoma (RAS) proteins regulate signalling, which is essential for both healthy growth and the development of cancer. Rational treatments that target RAS pathways have the potential to inhibit the growth and spread of tumours. New treatments are still being developed, and they are showing promise in clinical settings. The roles of receptors on tumour cells, their significance for cancer therapy, and recent advancements in preclinical and clinical research are all included in this overview. Review Fri, 15 Sep 2023 00:00:00 GMT MohsinaPatwekar, FaheemPatwekar, AnuradhaMedikeri, ShaikhDaniyal, Mohammad A.Kamal, Gulzar AhmedRather, RohitSharma, Fri, 15 Sep 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001166 https://www.explorationpub.com/Journals/em/Article/1001167 Diabetes mellitus has become increasingly more common and diagnosed within the global population. Coupled with the continued prevalence of substance use, there are some distinct considerations for users suffering (knowingly or unknowingly) from type 1 or type 2 diabetes. The various different types of drugs of abuse including central nervous system stimulants, depressants, and hallucinogens present varying direct and indirect complications for diabetes based on their physiological and psychological effects ranging from non-compliance with medication to an increased risk of hypoglycaemia, hyperglycaemia, and/or ketoacidosis. This perspective highlights these issues supported by the drug history and toxicological findings in patients undergoing drug rehabilitation in the United Arab Emirates (UAE) demonstrating the use of alcohol, amphetamines, benzodiazepines, cannabis, opiates/opioids (especially tramadol), pregabalin, and synthetic cannabinoids. Physicians and drug clinic professionals should be aware of the contraindications of substance use and diabetes with a view to educating patients and healthcare professionals within such clinical settings. Perspective Sun, 08 Oct 2023 00:00:00 GMT Abuelgasim Elrasheed A.Alhassan, WeaamElrashid, ArefAlshehhi, SamyaAl Mamari, MahmoudAbu Raddaha, MansourAssaf, SimonElliott, Sun, 08 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001167 https://www.explorationpub.com/Journals/em/Article/1001168 Self-replicating RNA viruses such as alphaviruses, flaviviruses, paramyxoviruses, and rhabdoviruses have been engineered as expression vectors for vaccine development. The prominent feature of self-replicating RNA viruses is their RNA-dependent RNA polymerase activity, which generates massive self-amplification of RNA in the cytoplasm of infected host cells leading to extreme levels of transgene expression. Infectious diseases have been targeted by overexpression of surface proteins of pathogens as antigens for vaccine development. Moreover, overexpression of tumor-associated antigens and immunostimulatory genes has been the basis for cancer vaccines. Proof-of-concept of robust antigen-specific immune responses and protection against challenges with lethal doses of infectious agents have been demonstrated. Likewise, vaccine development against various cancers has elicited strong immune responses and resulted in tumor regression and eradication, cure, and prolonged survival in animal tumor models. Good safety and immune responses have been achieved in clinical trials. The ERVEBO® vaccine, based on the vesicular stomatitis virus, has been approved for immunization against the Ebola virus disease. Review Tue, 10 Oct 2023 00:00:00 GMT KennethLundstrom, Tue, 10 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001168 https://www.explorationpub.com/Journals/em/Article/1001169 Bell’s palsy is a rapid unilateral peripheral paralysis of cranial nerve VII whose etiology is varied, most commonly associated with an acute infectious or inflammatory demyelinating process. Nerve injury can result in edema because of increased permeability of vascular structures, which can sometimes be seen as a locus of enhancement of magnetic resonance imaging (MRI). Bell’s palsy is typically considered a clinical diagnosis and the specificity and sensitivity of imaging have been poorly studied. Herein is describe a case of a 73-year-old male who presented to the emergency department with left-sided facial droop and no other focal neurological abnormalities. With a history of a Janus kinase 2 (JAK2) mutation and the new initial facial drooping, acute cerebrovascular insult was high on the differential. Initial labs and computerized tomography (CT) head were inconclusive, but MRI showed pronounced enhancement of the left distal internal carotid artery (ICA) with contiguous enhancement of the labyrinthine, geniculate, and tympanic segments of the left facial nerve. Diagnosing Bell’s palsy can be a challenge as there are numerous postulated etiologies stemming from trauma, infection, and neoplasm; with infection (particularly viral) postulated to be the most likely source. Though MRI is currently not validated as a tool in expediting Bell’s palsy diagnosis, findings such as the enhancement seen here provide some insight into the benefit of MRI as a diagnostic modality in some cases. This case is unique both for the diagnostic dilemma between stroke and Bell’s palsy and the potential for MRI imaging to help guide clinical decision-making into treatment. Case Report Mon, 23 Oct 2023 00:00:00 GMT AlvaroAlvarez, AsifBecher, Thomas ChandyVarkey, AvtarSingh, Mon, 23 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001169 https://www.explorationpub.com/Journals/em/Article/1001170 Aim: Parkinson’s disease (PD) is a complex, chronic neurodegenerative disorder with predominately sporadic etiology. Intricate genetic-environmental interactions lead to the hallmarks of the disease: degeneration of dopaminergic neurons and the deposition of α-synuclein aggregates. The aim of this study was to establish a novel primary patient cell model as an in vitro screen to study α-synuclein processing for drug screening. Methods: Primary patient olfactory neuroepithelial-derived cells (ONS) were exposed to α-synuclein and examined for cytotoxicity, processing, and solubility over 48 h. Epigallocatechin gallate (EGCG), which is known to destabilise α-synuclein fibrils, was used to investigate the solubilisation of α-synuclein in the model system. Results: Exposure to 0.1 μmol/L α-synuclein preformed fibrils was not toxic to ONS over 48 h. ONS processing of α-synuclein was observed to be different in PD cells by their increased accumulation in the cytoplasm. Processing deficits in the PD ONS were confirmed by immunoblotting with an increase in sodium dodecyl sulfate (SDS)-insoluble α-synuclein after 48 h. Conclusions: The data has illustrated the utility of primary patient ONS as a model system to understand the processing of α-synuclein. Considerable differences in α-synuclein processing were identified in PD ONS. Furthermore, the data suggests that primary patient ONS are a viable in vitro drug screening platform for α-synuclein pathology in PD. Original Article Wed, 25 Oct 2023 00:00:00 GMT Jessica K.Smith, George D.Mellick, Alex M.Sykes, Wed, 25 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001170 https://www.explorationpub.com/Journals/em/Article/1001171 Aim: Cannabis use for sleep-related problems is on the rise; however, little is known about the cannabis products people are using for sleep or the perceived effects of cannabis in comparison to more conventional sleep aids. Therefore, the aim of this study was to examine the products cannabis users prefer to use for sleep as well as their experiences with cannabis relative to more conventional sleep aids. Methods: De-identified archival data from a Strainprint® survey of 1,216 individuals who use cannabis for sleep were analyzed. Results: Participants predominantly reported smoking joints or vaping flower as their methods of administration, and seeking tetrahydrocannabinol (THC), cannabidiol (CBD), and the terpene myrcene in the cannabis they use for sleep. Only a small minority reported using cannabis in conjunction with conventional sleep aids. Comparisons of the self-reported effects of cannabis to conventional sleep aids revealed that participants reported feeling more refreshed, focused, better able to function, fewer headaches, and less nausea the morning after using cannabis for sleep than after using more conventional sleep aids or no sleep aids. However, they indicated they were more sleepy, anxious, and irritable in the mornings following the use of cannabis relative to other sleep aids. Participants were more likely to report red eyes and thirst and less likely to report nausea, anxiety, paranoia, and racing heart as side effects of cannabis relative to other sleep aids. Conclusions: Knowledge gained from this survey will provide health professionals with a better understanding of why people are using cannabis for sleep and may help guide future more controlled research. Original Article Wed, 25 Oct 2023 00:00:00 GMT AmandaStueber, CarrieCuttler, Wed, 25 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001171 https://www.explorationpub.com/Journals/em/Article/1001172 Oral cancer is the most common carcinoma of head and neck cancers. The majority of oral cancers are oral squamous cell carcinoma (OSCC). Among the various etiological factors, oral microbes—bacteria are also associated with pathogenesis of OSCC. But only few studies have been done associating the presence of oral bacteriome with OSCC. The main aim of this review is to focus on association of microbes with OSCC, the pathogenesis, variation in bacteriome profiling in different geographic conditions, their role in pathogenesis of OSCC, and different samples and methods that are used to study their association with habits and tumour node metastasis (TNM) staging. To conclude, the imbalance in the oral bacteriome could be considered an etiological factor for OSCC. Since the bacteriome profiling varies greatly with geographic location and even in an individual in different locations of the oral cavity, it advocates more research. The study on identifying bacteria associated with OSCC will also enable their use as diagnostic markers and preventive management of OSCC. Review Fri, 27 Oct 2023 00:00:00 GMT KarthikaPanneerselvam, Sathish KumarMahadevan, RamyaRamadoss, RajkumarKrishnan, MathanMohan, Fri, 27 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001172 https://www.explorationpub.com/Journals/em/Article/1001173 This case report demonstrates the successful induction of apexogenesis in an extensively carious lower right first molar with immature roots through the use of stepwise excavation and calcium-enriched mixture (CEM) cement as an indirect pulp capping material. The patient, an 8-year-old boy, presented with pain and carious pulp exposure. The initial treatment involved removing soft dentin and applying CEM cement as an indirect pulp cap. The patient experienced pain relief after 24 h, and subsequent follow-up appointments showed complete healing and maturation of the tooth. The case highlights the potential of indirect pulp treatment with CEM cement and emphasizes the importance of regenerative biomaterials in promoting healing and dentin bridge formation. Further clinical work and research are recommended to explore the efficacy of this treatment approach. Case Report Fri, 27 Oct 2023 00:00:00 GMT SaeedAsgary, LalehAlim Marvasti, Fri, 27 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001173 https://www.explorationpub.com/Journals/em/Article/1001174 The patient is a 58-year-old male who presented with chief complaints of right-sided numbness, tingling, and loss of temperature sensation in the upper and lower extremities. The patient’s symptoms began around the face and right corner of the mouth [maxillary/mandibular (V2/V3) distribution] before descending to the arm, trunk, and followed by the lower leg and foot. His home medication regimen included lisinopril, atorvastatin, long and short-acting insulin, and amlodipine. During the interview, the patient admitted to abstinence from his medications. Upon examination, the patient was found to have a loss of hot and cold touch on the right side and expressed 2+ reflexes (brisk response; normal) on both upper and lower extremities. In the initial work-up of the patient, he received a computed tomography (CT) scan which demonstrated an area of potential ischemic infarct of one of the left sided pontine perforator arteries. Immediately at that time he was given a loading dose of 325 mg aspirin and started on 81 mg daily. Because of the patient’s symptoms and risk factors, he was hospitalized for further additional work-up and eventually discharged on dual antiplatelet therapy. This case is intriguing as both neuroradiological reading and neurological examination helped with localization of the lesion and changing the treatment strategy of the patient. With a pontine perforator ischemic event, the harms of treatment with thrombolytics would have outweighed the benefits. This interprofessional work between neuroradiology, internal medicine, and neurology ensured that the patient received the best care for his specific ailments. Case Report Fri, 27 Oct 2023 00:00:00 GMT Zachary I.Merhavy, Garrett D.Barfoot, LeahDajani, ZainabElmahmoud, EmmanuelFlores, Thomas C.Varkey, Fri, 27 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001174 https://www.explorationpub.com/Journals/em/Article/1001175 Infection and suppuration of chronic wounds reduce the effectiveness of their treatment with a course of antibiotics and antiseptics combined with frequently renewed dressings. Therefore, daily short-term procedures of cleaning wounds from purulent-necrotic masses by mechanical methods, including the use of cleansing solutions and necrophage fly larvae, are also part of the general practice of chronic wound treatment. But even they do not always provide rapid healing of chronic wounds. In this connection, it is suggested to supplement the treatment of chronic wounds with preparations dissolving dense pus and wound dressings made in the form of warm moist compresses creating a local greenhouse effect in the wounds. Solutions of 3% hydrogen peroxide and 2–10% sodium bicarbonate heated to a temperature of 37°–45°С, possessing alkaline activity at рН 8.4–8.5 and enriched with dissolved carbon dioxide or oxygen gas (due to overpressure of 0.2 atm were suggested as pyolytic drugs. The first results of the use of pyolytics and warm moist dressings-compresses in the treatment of chronic wounds demonstrate a wound-healing effect. It is suggested to consider sanitizing therapy with pyolytics and warm moist wound dressings-compresses as an alternative to the use of modern cleansing solutions and artificial introduction of larvae of the necrophage fly into the purulent masses of chronic wounds to dissolve dense pus and accelerate the healing process. Perspective Fri, 27 Oct 2023 00:00:00 GMT AleksandrUrakov, NatalyaUrakova, EvgeniyFisher, AlbinaShchemeleva, AnastasiaStolyarenko, ValentinaMartiusheva, MarinaZavarzina, Fri, 27 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001175 https://www.explorationpub.com/Journals/em/Article/1001181 Aim: Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 has undergone several mutations, and ultimately, Indonesia was designated the Asian epicenter of the pandemic in 2021 due to the emergence of Delta variant SARS-CoV-2. Therefore, this study aimed to determine the characteristics of the Delta variant SARS-CoV-2 gene mutations. Methods: This is a cross-sectional descriptive study to determine the mutation characteristics of the Delta variant SARS-CoV-2 with data collected from patients’ medical records and whole genome sequencing (WGS). Results: The forty-nine patients who contracted the Delta variant SARS-CoV-2 were mainly aged 31−45 years and female. Four sublineages were identified, namely AY.23 (69.39%), AY.24 (22.45%), B.1.617.2 (6.12%), and AY.62 (2.04%), with fever and malaise being the most common clinical manifestations (79.60%). Furthermore, the spike (S) protein was most frequently mutated (12 mutations), with mutations in the Delta variant SARS-CoV-2 membrane (M) protein, nucleocapsid (N) protein, open reading frame (ORF), and nonstructural protein (NSP) also identified. Conclusions: The most common Delta variant SARS-CoV-2 sublineage in the current study cohort was AY.23, with the S protein being most frequently mutated. Continuous genomic surveillance is required to contain future outbreaks or infection waves, especially during the COVID-19 pandemic. Original Article Wed, 01 Nov 2023 00:00:00 GMT PheyLiana, Muhammad AgungMaulana, EnyRahmawati, Rouly PolaPasaribu, Kemas YakubRahadiyanto, Nelda ApriliaSalim, Tungki PratamaUmar, Wed, 01 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001181 https://www.explorationpub.com/Journals/em/Article/1001176 The paper aims to review the possibilities of a complex transdisciplinary approach to forming health and longevity. Determinants of productive longevity (DPL) and health culture are reviewed; definitions of health, stress, and eustress, and their roles in active and productive longevity are given. DPL making a decisive contribution to the phenomenon of active longevity are stated and analyzed from the point of view of evidence-based medicine. They are as follows: 1) environmental factors including geographical location, “Blue zones”, and mountain areas, as well as level of the environmental pollution; 2) dietary regimen to support active longevity, including vegetarianism, calorie restriction, fasting, the role of vitamins, biological antioxidants, geroprotectors, and micronutrients; 3) importance of activity and eustress phenomenon, by other words, lifestyle: physical activity, sexual relationship, Qigong and Yoga practices, cognitive activity, sense of humor, and acceptance of age in activities of daily living and survival; 4) genetic and epigenetic particularities as a condition for long-living; 5) level of health care and early diagnostics to prevent age-associated diseases; 6) the role of the state of mind and meditation as well, how it is used for forming health due to Qigong and Yoga natural systems, in religion, and medical practice; 7) motivation for active longevity that significantly increases chances to productive longevity. Review Mon, 30 Oct 2023 00:00:00 GMT Renad I.Zhdanov, Rustem N.Khayrullin, Rovshan I.Khalilov, AzizEftekhari, Alexey S.Sozinov, Mon, 30 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001176 https://www.explorationpub.com/Journals/em/Article/1001177 Radiation is a primary therapy in the treatment of thoracic malignancies with clear survival benefits. Consequently, patients with cancer are living longer but may be subject to a wide array of cardiotoxic effects from collateral radiation damage. Ensuing fibrosis can affect any portion of the cardiac parenchyma, increasing the risk for accelerated coronary artery disease, pericardial sequelae such as constrictive pericarditis, valvulopathy, restrictive cardiomyopathy, and a myriad of conduction system abnormalities. Unfortunately, the effects of cardiotoxicity can be subclinical or delayed and there remains an unmet need to standardize management strategies for these patients. Based on current data, it is prudent to consider percutaneous approaches first for coronary and valvular disease and traditional, supportive measures for the remaining sequelae. Every attempt should be made to undergo a complete operative haul due to the increased risks of re-operation if surgery is to be performed. Surrounding the patient with a multidisciplinary heart team is critical. Review Mon, 30 Oct 2023 00:00:00 GMT ChiragMehta, PuneetSingh, JessBrar, Mon, 30 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001177 https://www.explorationpub.com/Journals/em/Article/1001178 The prevalence of skin cancer has increased hastily in the recent decade for both kinds of melanoma and non-melanoma skin cancer. Skin cancers mostly encompass keratinocyte cancers: cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma. This review discusses the recent advancements in the treatment of skin cancer. In addition to chemotherapy, immunotherapy, targeted therapy, and photodynamic therapy (PDT), there are several other therapies for skin cancer. Additionally, PDT use in combination with chemotherapy, radiation, immunotherapy, and surgery is being actively investigated. This review will specifically address the pathophysiology of skin cancer, diagnostic approaches, and current therapies used in the topical treatment of skin cancers and introduce emerging treatment using nanotechnology that may be beneficial for these indications. Review Wed, 01 Nov 2023 00:00:00 GMT RajatGoyal, ShaheenHusain, KashishWilson, HiteshChopra, RakeshPahwa, MathumalarLoganathan, RohitSharma, Wed, 01 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001178 https://www.explorationpub.com/Journals/em/Article/1001179 Since the early 1970s, the U.S. Food and Drug Administration (FDA) has received over 800 investigational new drug applications (INDs) for, and pre-INDs pertaining to, research of cannabis or cannabis-derived products. The current data show that applications for research of these products submitted by both academic researchers and commercial developers focus on four major clinical areas: addiction and pain medicine (53%), neurology (19%), immunology and inflammation (14%), and psychiatry (9%). The product types studied have expanded greatly in recent years and include a wide variety of topical, inhalable, injectable, and oral products. In this article, the authors present a breakdown of cannabis and cannabis-derived applications received by the FDA over the past 50 years. The authors also provide a summary of their experience and challenges in reviewing applications for research of cannabis and cannabis-derived products, as well as recommendations for those interested in studying cannabis and cannabis-derived products in human clinical trials. This perspective article includes a discussion on important IND criteria, the pre-IND consultation program, drug master files (DMFs), and various guidance documents and resources. Lastly, the authors provide their perspective for the future of cannabis drug development. Perspective Wed, 01 Nov 2023 00:00:00 GMT Cassandra L.Taylor, Schuyler A.Pruyn, Wed, 01 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001179 https://www.explorationpub.com/Journals/em/Article/1001180 Progeroid syndromes are characterized by clinical signs of premature ageing, which may contain several diseases such as Werner syndrome, Bloom syndrome, Rothmund-Thomson syndrome, Hutchinson-Gilford progeria syndrome, and Cockayne syndrome. These disorders may also exhibit some pathological involvements reminiscent of primary mitochondrial diseases. Emerging evidence has linked mitochondria even to physiological ageing. In addition, alterations in the maintenance pathway of mitochondria have been also deliberated as relevant in age-related diseases. In particular, mitophagy and its regulatory pathway might be key process for the homeostasis of mitochondria. Therefore, chronic DNA damage and/or the activation of poly[adenosine diphosphate (ADP)-ribose] polymerase 1 (PARP1) could be a threat to the mitochondrial alterations. The PARP1 is an enzyme responding to the DNA damage, which might be also involved in the mitophagy. Interestingly, the PARP1 has been reported to play an important role in the longevity of lifespan, which has attracted growing attention with the social development. This review may provide a rationalized overview of the involvement of mitochondrial oxidative stresses in genetically defined accelerated ageing, progeroid syndromes, physiological ageing, and/or age-related diseases for the innovative therapeutic approaches. Review Wed, 01 Nov 2023 00:00:00 GMT NaokoSuga, YukaIkeda, SayuriYoshikawa, SatoruMatsuda, Wed, 01 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001180 https://www.explorationpub.com/Journals/em/Article/1001184 Type 1 diabetes is a chronic condition that results from the destruction of insulin-producing β-cells in the pancreas. Current treatments for type 1 diabetes, such as insulin therapy and pancreatic islet transplantation, have several limitations and, hence not quite effective in the long run. As current therapy methods fail to slow disease development, novel strategies such as the development of a bioartificial pancreas are being seriously considered. Over the last decade, research has focused on tissue engineering, which aids in the design of biological alternatives for the repair and replacement of non-functional or damaged organs. Three dimensional (3D) bioprinting technology which employs 3D printing technology to generate 3D tissue-like structures from biomaterials and cells, offers a promising solution for the treatment of type 1 diabetes by providing the ability to generate functional endocrine pancreatic tissue. Bioprinted structures are therefore an important aspect of tissue engineering because they have been found to replicate the native extracellular matrix, promoting cell survival and proliferation. In this review, recent developments in 3D bioprinting of endocrine pancreas for the treatment of type 1 diabetes particularly focussing on the choice of cells, biomaterials, growth factors, and essential considerations have been discussed in detail. Additionally, the key challenges and perspectives towards recapitulation of the pancreatic function of the pancreatic organ engineering technologies have also been discussed. Review Wed, 06 Dec 2023 00:00:00 GMT AnushikhaGhosh, ArkaSanyal, AbhikMallick, Wed, 06 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001184 https://www.explorationpub.com/Journals/em/Article/1001182 Amazingly, almost 50 years after the first demonstration of anticancer effects of cannabinoids in vitro and in vivo, well-designed clinical trials that definitively prove tumour-inhibiting effects in man are still missing. Whereas a large number of preclinical studies exist that describe tumour-inhibiting effects of cannabinoids, alone or in combination, but also in the form of medical cannabis or natural extracts in vitro, the number of in vivo studies is still limited. Even more limited are well-documented experiences in man. Most animal studies and experience with cannabinoids in man concern brain tumours. This review summarises the effects of phytocannabinoids in brain, breast, colorectal, head and neck, haematological, liver, lung, pancreatic, ovarian, prostate, and skin cancers in animal models and, if available, in patients. The large majority of animal studies demonstrate tumour-inhibiting effects of cannabinoids, thus confirming in vitro data. Experiences in cancer patients are almost exclusively limited to individual case reports and case series without a control group. Many questions are currently unanswered such as the role of pure cannabinoids compared to combinations, cannabinoids as the eventual sole cancer therapy, optimal dosages, or duration of treatment. Pure cannabidiol (CBD) seems to be superior to pure delta-9-tetrahydrocannabinol (THC) in experimental settings. The role of medical cannabis or extracts is less clear as they vary in their phytochemical composition. In conclusion, cannabis/cannabinoids may slow the progression of tumours. However, the hope that cannabinoids could eventually cure cancer as often spread in social media, is, at present, wishful thinking. Above all, well-designed clinical trials paired with long-term follow-up of cancer patients are needed. Review Wed, 06 Dec 2023 00:00:00 GMT GerhardNahler, Wed, 06 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001182 https://www.explorationpub.com/Journals/em/Article/1001183 Aim: Estrogen has an important role in the colonization of Candida through the presence of estrogen receptors (ERs). These ERs are usually used to categorize breast cancer into two types, positive and negative ER breast cancers. The effect of variation in the type of ER and estrogen levels on the biodiversity of Candida in the vagina was investigated. Methods: A case-control study, consisting of three groups of 30 patients with ER-positive, 29 with ER-negative breast cancer, and 30 healthy individuals, was carried out. The diversity and counting of Candida spp. in the vagina and estrogen levels were identified in all subjects. Results: The growth of Candida spp. was high in the vagina of patients with ER-positive breast cancer when estrogen was at normal levels. Otherwise, its growth was enhanced by high levels of estrogen in patients with ER-negative breast cancer. Conclusions: Estrogen levels have no effect on the vaginal content of Candida spp. in patients with ER-positive breast cancer, unlike those with ER-negative breast cancer. The principal recommendation from this study is that vaginal candidiasis and estrogen levels should be checked in patients with ER-negative breast cancer. Original Article Wed, 06 Dec 2023 00:00:00 GMT Ali Abdul Hussein S.AL-Janabi, Ruaa KadhimMohammed Jawad, Abdul Razzak KalafHassan, Wed, 06 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001183 https://www.explorationpub.com/Journals/em/Article/1001185 Protein kinases, a family of enzymes responsible for regulating various cellular processes, have been implicated in the development and progression of various heart diseases, making them attractive therapeutic targets. This review focuses on the role of protein kinases induced phosphorylation and protein phosphatase-induced dephosphorylation in cardiovascular disorders, including heart failure, ischemic heart disease, arrhythmias, hypertension, and diabetic cardiomyopathy. This paper explores the potential of novel kinase-targeted therapies and emerging technologies for the prevention and treatment of these conditions. It also discusses the involvement of protein kinase A (PKA), protein kinase C (PKC), phosphoinositide 3-kinases (PI3Ks), mitogen-activated protein kinases (MAPKs), and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in heart dysfunction and alterations in their function that contribute to their respective cardiac disorders. Furthermore, this article presents a comprehensive overview of protein kinases in cardiac disorders and the potential of innovative kinase-targeted therapies, advanced technologies, and multidisciplinary approaches for the effective prevention and treatment of cardiovascular diseases, ultimately aiming to improve patient outcomes and quality of life. Review Fri, 08 Dec 2023 00:00:00 GMT JaykrishanPrasad, Anureet K.Shah, Naranjan S.Dhalla, Fri, 08 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001185 https://www.explorationpub.com/Journals/em/Article/1001186 Aim: The aim is to analyze the microbiome of gingival sulcus and periodontal pockets of patients with periodontal disease associated with systemic diseases. Methods: A microbiological study was conducted to analyze the microflora of the periodontal pockets in patients with different systemic pathologies and periodontal diseases. Plaque samples were collected from the gingival sulcus and periodontal pockets, and they were subsequently cultured on nutrient medium and glass plates. Results: The microbiota of the gingival sulcus and periodontal pockets in patients with associated systemic diseases in combination with periodontal disease was studied. The frequency of detecting the qualitative composition of the microbiota in the periodontal niche of patients with periodontal diseases and systemic diseases was determined. The research paper outlined groups of microorganisms isolated from periodontal pockets of patients with periodontal and systemic diseases. Conclusions: The degree of colonization by microorganisms differed slightly, while the frequency of detection of specific populations of opportunistic bacteria increased in chronic generalized periodontitis compared to chronic catarrhal gingivitis. Original Article Mon, 11 Dec 2023 00:00:00 GMT OlhaDenefil, SofiiaChorniy, SvitlanaBoitsaniuk, NadiiaManashchuk, NataliaChornij, MarianaLevkiv, NataliaTverdokhlib, KhrystynaLoza, Mon, 11 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001186 https://www.explorationpub.com/Journals/em/Article/1001187 Lung tuberculosis (TB) remains a heavy burden on public health worldwide. This review discusses mainly the mechanisms of the development of pulmonary fibrosis in an experimental TB model in mice. The involvement of individual components of the extracellular matrix, the activity of matrix metalloproteinases, and the role of their tissue inhibitors in the fibrosis development. The current TB therapy activates fibrosis along with anti-mycobacterial action. The paper describes the authors’ results of experimental use of the liposome-encapsulated dextrazid (LЕDZ) combined with isoniazid (INH) which has both antifibrotic and anti-mycobacterial effects to be considered for future treatment. Review Tue, 12 Dec 2023 00:00:00 GMT Lena B.Kim, Anna N.Putyatina, Tue, 12 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001187 https://www.explorationpub.com/Journals/em/Article/1001188 Aim: The frequency of severe acute malnutrition (SAM) is the highest in India. Although it should receive more attention, severe anemia is one of the comorbidities that increases mortality in children who are severely undernourished. In SAM children, the liver function test (LFT), kidney function test (KFT), and complete blood count (CBC) are deranged, but their correlation with the prognosis is not well defined. The aim was to describe the anthropometric assessment and biochemical profile of children with SAM. Methods: This cross-sectional cohort study was performed at the Departments of Paediatrics and Biochemistry at G.S.V.M. Medical College, Kanpur, and at the Department of Biotechnology at Amity University Rajasthan, Jaipur. One hundred and six patients with SAM were enrolled; 53 were grouped as complicated SAM (Group 1) (dehydration and severe dehydration) and 53 were diagnosed as non-complicated SAM (Group 2). Results: Group II had significantly higher mean values for height, weight, mid-upper arm circumference (MUAC), head circumference, and body mass index (BMI) for age percentile compared to Group I, with P-values of 0.001. Group I had a significantly lower level of hemoglobin (8.86 g/dL ± 2.21 g/dL) compared to Group II (10.0 g/dL ± 1.83 g/dL) with a P-value of 0.003. The difference in the frequency of anemia between the groups was statistically significant, with a P-value of 0.026. Anemia significantly increased the risk of complicated SAM with an odds ratio of 2.60 [95% confidence interval (CI), 1.07–6.31, P = 0.001]. Conclusions: This study suggests that there may be a significant relationship between anemia and the development of complications in high-risk children with SAM. Original Article Mon, 25 Dec 2023 00:00:00 GMT MalvikaMishra, PrashantTripathi, PratibhaSingh, Yashwant KumarRao, Desh DeepakSingh, Mon, 25 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001188 https://www.explorationpub.com/Journals/em/Article/1001189 Effective clinical management of women with schizophrenia is therapeutically challenging. While there have been recent advances in the understanding of neurobiological, hormonal, and female reproductive cycle factors that play a decisive role in the development and progression of schizophrenia in women, this knowledge has not yet been fully translated into treatment practice. The aim was to apply the best evidence available to optimally treat women with schizophrenia at various periods of the lifespan. A narrative review was conducted of recent advances (2018–2023) in aspects of schizophrenia in women that demand sex-specific treatment. Sex steroids impact antipsychotic absorption, distribution, metabolism, elimination, passage through the blood-brain barrier, and blood flow rate to the brain. For these reasons, premenopausal women with schizophrenia, as compared to male age peers, require lower doses of most antipsychotic drugs and suffer comparatively more adverse events (metabolic, sexual, and cardiovascular) at similar doses. Apart from pharmacologic treatment, women have specific reproductive planning needs and need protection from sexual exploitation and domestic abuse. In addition, when pregnant, schizophrenia women show a high risk of gestational diabetes and pre-eclampsia/eclampsia that requires prevention. Prevention is also needed against long-term health hazards for their offspring. Another period of therapeutic challenge specific to women is menopause. The collected evidence points to women-specific recommendations for both biological and psychosocial treatment strategies for schizophrenia. Review Mon, 25 Dec 2023 00:00:00 GMT AlexandreGonzález-Rodríguez, JesúsCobo, Mary V.Seeman, Mon, 25 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001189 https://www.explorationpub.com/Journals/em/Article/1001190 The gut microbiota comprises a complex bacterial community that resides in the intestine. Imbalances in the gut microbiota can disrupt immune homeostasis, triggering autoimmune diseases including non-infectious uveitis. Despite recent advances, the underlying mechanisms linking the microbiome and uveitis are not fully understood. This review offers a comprehensive analysis of the literature addressing microbiome’s relationship with ocular inflammation. Additionally, it explores the potential of modulating the gut microbiota as a novel therapeutic target. A literature search of published articles related to the role of ocular microbiome in non-infectious uveitis in PubMed and Scopus databases was conducted. The following keywords were used: microbiome, uveitis, and immune-mediate diseases. Review Mon, 25 Dec 2023 00:00:00 GMT HindAmin, SamirShoughy, Mon, 25 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001190 https://www.explorationpub.com/Journals/em/Article/1001191 Nocturnal heartburn (NHB) is a symptom that affects up to 25% of the general population and has been shown to cause sleep disruption that adversely affects quality of life and psychomotor performance. Few studies have evaluated the association between occasional NHB and sleep disturbances; therefore, this connection may be underappreciated and left untreated by the primary care provider and patient, with potentially significant negative clinical consequences and effects on quality of life. This review sought to describe what is currently known about the interplay between occasional NHB and sleep disruption, and identify whether acid suppression therapy can improve symptoms of occasional NHB and associated sleep disruptions. The pathophysiology of heartburn-induced sleep disruption appears to follow a bidirectional cycle due to the normal physiologic changes that occur in the upper gastrointestinal tract during sleep and due to the potential for heartburn symptoms to cause sleep arousal. The majority of the identified studies suggested that pharmacologic interventions for acid reduction, including proton pump inhibitors or histamine type-2 receptor antagonists (H2RAs), improved objective and/or subjective sleep outcomes among individuals with gastroesophageal reflux disease (GERD) and NHB. Several studies specific to famotidine demonstrated that treatment with 10 mg or 20 mg reduced nighttime awakenings due to NHB. In conclusion, NHB symptoms can cause sleep dysfunction that can have a profound adverse downstream effect on quality of life, next-day functioning, and health-related outcomes. The current approach to managing occasional NHB is similar to that associated with GERD, highlighting the need for studies specific to the occasional heartburn population. Health care providers should investigate NHB as one of the potential causes of sleep complaints, and patients with heartburn should be questioned about sleep quality, recalled arousals, next-day vitality, early fatigue, and next-day functioning. Review Mon, 25 Dec 2023 00:00:00 GMT David A.Johnson, Amisha M.Parikh-Das, EvrenAtillasoy, HaykDavtyan, LeslieShur, Andrea S.Blevins-Primeau, Nathaniel F.Watson, Mon, 25 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001191 https://www.explorationpub.com/Journals/em/Article/1001192 Within group A Streptococcus (GAS), only Streptococcus pyogenes exhibits clinical significance. GAS is typed serologically based on unique surface proteins and critical virulence factors, such as a hyaluronic acid capsule that shields GAS from phagocytosis. The burden of GAS was estimated in the last five years as 14,000 to 25,000 cases of the invasive group A streptococcal disease in the USA with an estimated death from 1,500 to 2,300 cases per year. Early in the summer of 2022 in England, there was more scarlet fever than was anticipated. Early in the current season, the number of notifications rose to unusual heights. The analysis of invasive GAS (iGAS) isolate typing data shows that this season has seen a wide variety of encoding mature M protein (emm) gene sequence types found. Therefore, public health authorities should think about initiatives to increase clinicians’ and the general public’s awareness of GAS infections and to promote their quick diagnosis, molecular testing and antibiotic susceptibility testing, and standard treatment. Commentary Fri, 29 Dec 2023 00:00:00 GMT KamranZaman, AbdelmonemSiddiq, AroopMohanty, Darwin A.León-Figueroa, Joshuan J.Barboza, TareqAL-Ahdal, RanjitSah, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001192 https://www.explorationpub.com/Journals/em/Article/1001193 Aim: Arthritis is a degenerative condition characterized by the progressive deterioration of the knee joint, leading to aches, rigidity, and decreased mobility. Total knee arthroplasty (TKA) surgery is performed to alleviate pain for restoring activity in these patients. TKA is carried out due to natural wear of the cartilage and meniscus or by sudden impact at the knee joint area. The surgical procedure involves careful planning, precise bone cuts, and insertion of artificial components made of metal alloys and high-density polyethylene. However, conventional manufacturing of customized knee implants involves time and cost. This work aims to present the application of three-dimensional (3D) printing for developing individualized knee implants for TKA and the challenges faced during it. Methods: Morphometry of the knee joint varies among different populations, including Indian and Western, which pose challenges during the surgery as accurate alignment and implant sizing are crucial for optimal outcomes. A female patient’s pre-surgery computed tomography (CT) scan is considered to identify the disease and to find region of interest (ROI) such as knee joint. Process involves converting scanned data to a file format for 3D printing via computer-aided design (CAD). Results: The patient’s CT scan data is processed to obtain the CAD models of knee joint and standard triangulation language (STL) file. Additional geometries and noise present near the region are removed to get ROI. Open loops and overlapping triangles are rectified in the STL file. Based on the morphometry of the bone, resection is done to obtain the CAD models of knee implants. 3D printing of the knee joint and implant prototypes is then obtained using fused deposition modelling (FDM). Line layers on the printed implant prototype are seen. Conclusions: Patient-specific 3D printed knee joint implant prototypes are successfully obtained using FDM. Challenges faced during the work are successfully worked out. Original Article Fri, 29 Dec 2023 00:00:00 GMT DasharathRamavath, Shivraj NarayanYeole, Jaya PrakashKode, NarendraPothula, Sudheer ReddyDevana, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001193 https://www.explorationpub.com/Journals/em/Article/1001194 Artificial intelligence (AI) studies are increasingly reporting successful results in the diagnosis and prognosis prediction of ophthalmological diseases as well as systemic disorders. The goal of this review is to detail how AI can be utilized in making diagnostic predictions to enhance the clinical setting. It is crucial to keep improving methods that emphasize clarity in AI models. This makes it possible to evaluate the information obtained from ocular imaging and easily incorporate it into therapeutic decision-making procedures. This will contribute to the wider acceptance and adoption of AI-based ocular imaging in healthcare settings combining advanced machine learning and deep learning techniques with new developments. Multiple studies were reviewed and evaluated, including AI-based algorithms, retinal images, fundus and optic nerve head (ONH) photographs, and extensive expert reviews. In these studies, carried out in various countries and laboratories of the world, it is seen those complex diagnoses, which can be detected systemic diseases from ophthalmological images, can be made much faster and with higher predictability, accuracy, sensitivity, and specificity, in addition to ophthalmological diseases, by comparing large numbers of images and teaching them to the computer. It is now clear that it can be taken advantage of AI to achieve diagnostic certainty. Collaboration between the fields of medicine and engineering foresees promising advances in improving the predictive accuracy and precision of future medical diagnoses achieved by training machines with this information. However, it is important to keep in mind that each new development requires new additions or updates to various social, psychological, ethical, and legal regulations. Review Fri, 29 Dec 2023 00:00:00 GMT Kadircan H.Keskinbora, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001194 https://www.explorationpub.com/Journals/em/Article/1001195 Aim: Respiratory failure is common after esophagectomy for esophageal cancer (EC). This study aimed to identify the risk factors associated with postoperative respiratory failure following esophagectomy for EC. Methods: A single-center observational study from China was conducted on 262 patients with EC who underwent thoracoscopic esophagectomy between April 2014 and June 2016. The patients were divided into two groups: group I (respiratory failure) and group II (without respiratory failure). Demographic and perioperative variables, tumor-related factors, surgical factors, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, and clinical course were compared between the groups. Univariable and multivariable logistic regression analyses were performed to assess the risk factors of postoperative respiratory failure after esophagectomy. Results: Among the 262 patients, 24 (9.2%) developed respiratory failure. Univariable analysis revealed several risk factors, including age, smoking, comorbidities, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), forced vital capacity (FVC), FVC percentage (FVC%), urine volume during surgery, and APACHE II score. Multivariable analysis showed that age, comorbidities of diabetes mellitus (DM), FVC%, urine volume during surgery, and APACHE II score were independent predictors of respiratory failure. Specifically, elderly patients (> 65 years) with comorbidities of DM, lower FVC%, higher urine volume during surgery, and elevated APACHE II score were found to be more susceptible to respiratory failure, resulting in prolonged hospitalization and increased healthcare burden. These findings emphasize the importance of considering these factors in the management and care of patients at risk of respiratory failure. Conclusions: As a common complication following esophagectomy for EC. Respiratory failure is significantly associated with age, comorbidities of DM, FVC%, urine volume during surgery, and APACHE II score in the dataset. The findings will contribute to the evaluation of the risk of respiratory failure and guide early intervention strategies in clinical decision-making. Original Article Fri, 29 Dec 2023 00:00:00 GMT ZhanglanFang, HaoYang, YiLong, DongyunXu, BenyuSu, ChaoXu, HuguangYang, FengXu, LingLuo, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001195 https://www.explorationpub.com/Journals/em/Article/1001196 Aim: Cholesterol is an essential component of cell membranes and serves as a precursor for several bioactive molecules, including steroid hormones and isoprenoids. Generally supplied by the bloodstream, the de novo cholesterol biosynthesis is activated in response to an increased cell requirement due to normal tissue remodeling or tumor proliferation. In estrogen receptor (ER)-positive breast cancers, cholesterol biosynthesis may promote and sustain tumor growth and concur with the failure of the treatment with aromatase inhibitors. Methods: In this study, the comparison of gene compared the expression involved in cholesterol biosynthesis was conducted in ER-positive tumors that were responsive and nonresponsive to letrozole; besides, an exploration of their association with genes implicated in estrogen production, the Hippo pathway, and cell cycle control was performed. Results: In responsive tumors, letrozole significantly decreased the expression of five genes [acetyl-coenzyme A (CoA) acetyltransferase 2 (ACAT2), 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), farnesyl diphosphate synthase (FDPS), and squalene epoxidase (SQLE)] crucial for the biosynthetic process. Conversely, in nonresponsive tumors, these genes were unaffected by letrozole but associated with several genes involved in estrogens production [cytochrome P450 family 19 subfamily A member 1 (CYP19A1), hydroxysteroid 17-beta dehydrogenase 2 (HSD17B2), and sulfotransferase family 1A member 1 (SULT1A1)], cell cycle [control cyclin dependent kinase 4 (CDK4) and CDK6], and Hippo pathway [Yes1 associated transcriptional regulator (YAP1) and baculoviral inhibitor of apoptosis (IAP) repeat containing 5 (BIRC5)]. Conclusions: The findings corroborated the notion that the dysregulation of the mevalonate pathway may contribute to the resistance to letrozole and supported the use of statins to contrast this metabolic dysfunction. Original Article Fri, 29 Dec 2023 00:00:00 GMT DanilaCoradini, FedericoAmbrogi, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001196 https://www.explorationpub.com/Journals/em/Article/1001197 Cancer cure with immunotherapy is an innovative step towards cancer treatment with better survivability, but it is mostly dependent on the response of the patient’s immune system to the immunotherapeutic approach. This descriptive review article emphasizes the conventional and advanced treatment modalities currently available for breast cancer management. This review also highlights the clinical management of breast cancer concerning immune response especially to unravel the prospects for manipulation of immune cells: such as lymphocytes, including T-cells, T-regulatory cells and natural killer cells, and others like macrophages, dendritic cells, and the panel of interleukins or interferons released by them which has made a significant impact on breast cancer research. In addition, an effort was made to emphasize the different clinical trials and their future implication for the reduction of breast cancer cases. Overall, an attempt has been made to shed light on the possibilities of immunotherapeutics in breast cancer care, as well as the role of immune response in the incidence, aggressiveness, and survival of breast cancer. Review Fri, 29 Dec 2023 00:00:00 GMT BanashreeBondhopadhyay, ShowketHussain, VishakhaKasherwal, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001197 https://www.explorationpub.com/Journals/em/Article/1001198 Gelotology (the study of laughter) has it seems mainly evaded the attention of longevity scientists, positive biologists, and geroscientists. However, the potential of laughter to result in immediate improved affect, increase overall well-being, reduce cortisol levels, benefit the immune system, and support cardiovascular health, to name only a few of its possible effects, renders it of high interest as an anti-aging strategy. As an intervention, laughter has, at least theoretically, the potential to slow the process of aging, and to ameliorate its lived experience. What makes laughter particularly attractive is that it is accessible to all, is very low risk, and is inherently, for most people, enjoyable. Ten years ago, lifestyle medics first proposed that laughter be prescribed in primary care. They pointed to its efficacy in general patient care, geriatrics, rheumatology, critical care, oncology, rehabilitation, psychiatry, home care, palliative care, terminal care, and hospice care. Nevertheless, laughter prescription has been slow to take off. It is therefore of interest to contemplate why, how, and to what effect, laughter can be harnessed to improve people’s lives. Quality research is recommended to uncover the secrets of laughter, its dynamic effects on the body, if, and how, it may impact longevity, and how it can best be used to promote successful and active aging. Commentary Fri, 29 Dec 2023 00:00:00 GMT FredaGonot-Schoupinsky, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001198 https://www.explorationpub.com/Journals/em/Article/1001199 Chronic obstructive pulmonary disease (COPD) is an inflammatory lung pathology characterized by persistent airflow limitation and is the third leading cause of death globally. COPD pathophysiology includes both environmental and host risk factors and the presence of comorbidities contributes to its harmful outcome. Cardiovascular disease (CVD) is closely related to COPD and their coexistence is associated with worse outcomes than either condition alone. COPD impairs the cardiovascular system favoring mostly endothelial dysfunction that is a significant COPD prognostic factor at different stages of the disease. The mechanisms promoting endothelial dysfunction in the systemic and/or pulmonary circulation of COPD patients are different and include systemic inflammation, alteration of adhesion and pro-inflammatory molecules, oxidative stress, cellular senescence, and apoptosis. Nevertheless, the role of endothelium in the onset and progression of COPD and CVD is not yet fully understood. Hence, the purpose of this narrative review is to analyze the literature and provide evidence supporting the importance of endothelial dysfunction in COPD. Review Fri, 29 Dec 2023 00:00:00 GMT SilviaSiragusa, GiuliaNatali, Antonella MariaNogara, MarcelloTrevisani, Costanza Anna MariaLagrasta, SilviaPontis, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001199 https://www.explorationpub.com/Journals/em/Article/1001200 The integration of three-dimensional (3D) printing techniques into the domains of biomedical research and personalized medicine highlights the evolving paradigm shifts within contemporary healthcare. This technological advancement signifies potential breakthroughs in patient-specific therapeutic interventions and innovations. This systematic review offers a critical assessment of the existing literature, elucidating the present status, inherent challenges, and prospective avenues of 3D printing in augmenting biomedical applications and formulating tailored medical strategies. Based on an exhaustive literature analysis comprising empirical studies, case studies, and extensive reviews from the past decade, pivotal sectors including tissue engineering, prosthetic development, drug delivery systems, and customized medical apparatuses are delineated. The advent of 3D printing provides precision in the fabrication of patient-centric implants, bio-structures, and devices, thereby mitigating associated risks. Concurrently, it facilitates the ideation of individualized drug delivery paradigms to optimize therapeutic outcomes. Notwithstanding these advancements, issues concerning material biocompatibility, regulatory compliance, and the economic implications of avant-garde printing techniques persist. To fully harness the transformative potential of 3D printing in healthcare, collaborative endeavors amongst academicians, clinicians, industrial entities, and regulatory bodies are paramount. With continued research and innovation, 3D printing is poised to redefine the trajectories of biomedical science and patient-centric care. The paper aims to justify the research objective of whether to what extent the integration of 3D printing technology in biomedicine enhances patient-specific treatment and contributes to improved healthcare outcomes. Review Fri, 29 Dec 2023 00:00:00 GMT KalyaniPathak, RiyaSaikia, AparoopDas, DibyajyotiDas, Md ArifulIslam, PallabPramanik, AbhishekParasar, Partha ProtimBorthakur, PranjalSarmah, MadhurjyaSaikia, BarbieBorthakur, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001200 https://www.explorationpub.com/Journals/em/Article/1001201 According to recent data reported, it is noted that lung cancer is the leading cause of cancer death internationally followed by cardiovascular diseases and diabetes. This disease is observed in both women and men and is related to lifestyle habits. Several causes are reported to be at the origin of lung cancer, especially smoking. It is important to note that the majority of lung cancers develop in the bronchi, that is to say at the level of the upper airways which lead to the lungs, which does not however make it possible to rule out the risk factors that come under environmental pollution since man breathes the air quality of the environment every day for his breathing. This review of the literature has made it possible to draw up a state of knowledge in order to understand the risk factors that increase lung cancer. More specifically, this work will make it possible to raise awareness in the field of the fight against cancer, in particular lung cancer. Review Fri, 29 Dec 2023 00:00:00 GMT HervéAgonsanou, RicardoFigueiredo, MauriceBergeron, Fri, 29 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001201 https://www.explorationpub.com/Journals/em/Article/1001202 Aim: In regenerative dentistry, the success is influenced by the graft material, which should act as an osteoconductive scaffold. It provides a mineral substrate during resorption and induces the activity of osteoinductive cells capable of producing new bone, platelet growth factors, and cell differentiation factors that guide the differentiation of undifferentiated mesenchymal cells. Given that dentin shares many biochemical characteristics with bone tissue, it has recently attracted considerable interest as a biomaterial for bone repair. The aim of this study is to compare two grinder types to determine the optimal method for producing dentinal particles using a mechanical grinder. Methods: A sample of 40 natural human teeth without restorations, prostheses, or root canal treatments was used and divided into two groups subjected to two different grinder speeds (high-speed and low-speed). Results: The high-speed showed a greater dispersion (53.5% ± 9.89% of the tooth) due to the pulverisation (highly thin granules) of part of the tooth. The low-speed grinder did not pulverize the dentin and the percentage of tooth loss is 9.16% ± 2.34%. Conclusions: The low-speed grinder allows to save a major part of the tooth and has a maximum quantity of graft material but requires more time. Further studies must be promoted to optimise the grinding procedures. Original Article Wed, 07 Feb 2024 00:00:00 GMT ElioMinetti, GiannaDipalma, AndreaPalermo, Alessio DaniloInchingolo, FabioViapiano, Angelo MicheleInchingolo, FrancescoInchingolo, Wed, 07 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001202 https://www.explorationpub.com/Journals/em/Article/1001203 Three-dimensional (3D) and four-dimensional (4D) printing have emerged as the next-generation fabrication technologies, covering a broad spectrum of areas, including construction, medicine, transportation, and textiles. 3D printing, also known as additive manufacturing (AM), allows the fabrication of complex structures with high precision via a layer-by-layer addition of various materials. On the other hand, 4D printing technology enables printing smart materials that can alter their shape, properties, and functions upon a stimulus, such as solvent, radiation, heat, pH, magnetism, current, pressure, and relative humidity (RH). Myriad of biomedical materials (BMMs) currently serve in many biomedical engineering fields aiding patients’ needs and expanding their life-span. 3D printing of BMMs provides geometries that are impossible via conventional processing techniques, while 4D printing yields dynamic BMMs, which are intended to be in long-term contact with biological systems owing to their time-dependent stimuli responsiveness. This review comprehensively covers the most recent technological advances in 3D and 4D printing towards fabricating BMMs for tissue engineering, drug delivery, surgical and diagnostic tools, and implants and prosthetics. In addition, the challenges and gaps of 3D and 4D printed BMMs, along with their future outlook, are also extensively discussed. The current review also addresses the scarcity in the literature on the composition, properties, and performances of 3D and 4D printed BMMs in medical applications and their pros and cons. Moreover, the content presented would be immensely beneficial for material scientists, chemists, and engineers engaged in AM manufacturing and clinicians in the biomedical field. Review Wed, 07 Feb 2024 00:00:00 GMT Gayan A.Appuhamillage, Sankalya S.Ambagaspitiya, Rohan S.Dassanayake, AchinthaWijenayake, Wed, 07 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001203 https://www.explorationpub.com/Journals/em/Article/1001204 Schizophrenia is a serious mental disorder affecting about 1% of the population. It is characterised by multiple symptoms which are mostly responsive to treatment with antipsychotic medications. Cognitive impairment is regarded as a core feature of illness which is mostly poorly responsive to treatment with the current antipsychotic medications. Improving cognitive function is an important treatment goal as it is associated with better outcomes in employment and quality of life. Adjunctive pharmacological treatments have been examined to improve measures of cognition but with limited success. Cannabidiol (CBD), has shown promise in preclinical models of cognitive deficits of schizophrenia. On the other hand, limited studies in small groups of patients with schizophrenia have shown no significant clinical benefits for cognitive function as an adjunct to ongoing treatment with antipsychotics. A single trial, in which CBD as a standalone treatment was compared to the antipsychotic medication amisulpride, showed significant changes in cognitive measures for both agents, with no statistically significant difference between them. It might therefore be concluded that the preclinical findings have failed to translate to the clinic. However, the preclinical findings themselves are based on a circumscribed set of studies in multiple cognitive models and have used varying doses and routes of drug administration. The same general methodological issues are present in the suite of clinical studies. Issues such as patient heterogeneity in terms of illness duration, formulation and dose of CBD employed, and length of cannabinoid treatment might militate positive findings. The limited clinical database available makes the benefits (or lack thereof) of CBD for the cognitive effects of schizophrenia uncertain. Continued research in much larger patient populations than have so far been investigated as well as a consideration of dose ranging studies are required to fully assess the potential risks against the benefits of CBD treatment for cognitive deficits in schizophrenia. Review Wed, 07 Feb 2024 00:00:00 GMT Trevor R.Norman, Wed, 07 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001204 https://www.explorationpub.com/Journals/em/Article/1001207 Aim: The aim of this study is to investigate the prevalence of human papillomavirus (HPV) genotypes in Moroccan women diagnosed with invasive cervical cancer and to assess the association between HPV infection and some socio-demographic characteristics and clinicopathological features. Methods: In this study, 80 fresh biopsies from patients with confirmed diagnoses of cervical cancer during the study period (2020–2021) were collected. All cases were subject to HPV detection by nested PCR using MY09/11 and GP5+/6+ primers. HPV genotyping was performed by type-specific PCR targeting HPV 6, 11, 16, 18, 31, and 33. Results: The average age of patients was 54 years. Most patients were diagnosed with squamous cell carcinoma (SCC; 82.5%) at stage II (71.3%). Overall, 91.3% of cervical cancer cases were HPV-positive. HPV 16 is the most prevalent genotype, reported in 60.3% of HPV-positive cases, followed by HPV 18, 33, and 31 genotypes, identified in 20.5%, 12.3%, and 6.8%, respectively. No double infection with these genotypes was observed. Statistical analysis showed a significant correlation between HPV infection and age at menarche (P = 0.028), parity (P = 0.004), childbirth delivery (P = 0.040), and marital status (P = 0.042). Conclusions: HPV-DNA was prevalent in most examined cervical cancer tissues and HPV 16, HPV 18, HPV 33, and HPV 31 were present, at single infection, in all HPV-positive cases. These results emphasize already reported data on HPV distribution in Morocco and may contribute significantly to promoting the use of HPV DNA-based screening tests and available vaccines to limit HPV infection, viral dissemination, and cancer cervical development. Original Article Wed, 28 Feb 2024 00:00:00 GMT Kaoutar AnouarTadlaoui, MustaphaBenhessou, AbdelilahLaraqui, LinaBenfdil, El ArbiBouaiti, Mohammed ElMzibri, Moulay MustaphaEnnaji, Wed, 28 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001207 https://www.explorationpub.com/Journals/em/Article/1001205 Atypical ductal hyperplasia (ADH) is a benign lesion of the breast that is associated with an increased risk of invasive breast cancer. This review explores the pathophysiology, risk factors for progression to breast cancer, and lifetime management for patients diagnosed with ADH on core needle biopsy (CNB). The management plan for patients diagnosed with ADH includes regular clinical surveillance, diagnostic mammography, along with risk-reduction strategies such as lifestyle modifications or the use of adjuvant endocrine therapies. This review aims to delve into the complexities of ADH from diagnosis to management to aid clinicians in finding the best way to approach this high-risk breast lesion. Mini Review Wed, 07 Feb 2024 00:00:00 GMT NadiaIslam, SuneelaVegunta, Wed, 07 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001205 https://www.explorationpub.com/Journals/em/Article/1001206 Acquired or hereditary epilepsy affects millions of people. Today, the disease is pharmacoresistant in about 30 percent of cases, meaning that the seizures do not come under acceptable control in response to medication. Therefore, there is a great need for the development of novel methods for epilepsy research and treatment. Although in vivo animal models best mimic the clinical features of epilepsy, in vitro models have clear advantages in elucidating the fine details and cellular mechanisms of neurological disorders. In contrast to short-lived experiments in acute brain slices, cell cultures are often chosen as chronic models for antiseizure medication screening and epilepsy research under reduced, well-controlled in vitro conditions that still include all major cell types susceptible to epileptic seizures. Organotypic brain slices or dissociated cells produce spontaneous synchronized epileptiform discharges classified as interictal and ictal-like. In addition, pharmacologically or electrically induced seizures and status epilepticus can be obtained for electrophysiological and imaging experiments. Relatively simple cell cultures of primary rodent neurons provide entry-level models for the initial screening of antiseizure medications and basic epilepsy research. However, more sophisticated human cultures of stem cell-derived neurons offer the possibility of medical studies using the human genotype without the need to obtain brain tissue from patients. As an evolution of this method, programmed differentiation of brain cells is now being used in stem cell therapy for neurological disorders. Overall, cell culture greatly expands the repertoire of methods available to study epileptic disorders and potential cures. Review Mon, 26 Feb 2024 00:00:00 GMT IlyaOblasov, OlgaIdzhilova, PavelBalaban, EvgenyNikitin, Mon, 26 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001206 https://www.explorationpub.com/Journals/em/Article/1001208 Nerve cell death is the central aspect of human neurodegenerative disorders. Neuronal death in results leads to the onset of various human neurological disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and stroke. In developing neurons, apoptosis is assumed to provide a counterbalance to overexuberant cell replication. Numerous signals may induce apoptosis in neurons, such as the absence of neurotrophic factor support, increased levels of metabolic and oxidative stress, and overstimulation of glutamate receptors (leading to the calcium influx). Cell death and neurological disorders have been related to oxidative stress, which creates an imbalance between antioxidant defenses and free radical production. In this paper, a summary of the engrossment of oxidative stress, neuronal apoptosis, and mitochondrial dysfunction in neurodegenerative disorders has been discussed. Antioxidant therapy’s potential assistance for neurodegenerative illnesses in human beings is still up for dispute, despite encouraging pre-clinical research findings. One elucidation for this disparity could be the non-existence of an accurate way to assess oxidative stress in the brain. The explosion in research on apoptosis in neurodegeneration has stemmed from the conception that persuading neuronal apoptotic death may be crucial to the progression of a disease and that anti-apoptotic approaches may be useful in the prevention of neurodegenerative processes. A deeper understanding of the role that apoptosis plays in neurodegenerative processes will serve as the foundation for future research into the development of focused, effective treatment modalities. Review Thu, 29 Feb 2024 00:00:00 GMT RajatGoyal, KashishWilson, AnjaliSaharan, Rupesh K.Gautam, HiteshChopra, SumeetGupta, MohammadAmjad Kamal, Thu, 29 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001208 https://www.explorationpub.com/Journals/em/Article/1001209 Aim: Although the prevalence of coronary heart disease (CHD) and hypertension which are the most common causes of the development and progression of chronic heart failure (CHF) is high, 24-hour ambulatory blood pressure (BP) monitoring (ABPM) in patients with CHF is not mandatory to be performed. The growing number of evidence suggests that excessive decrease in BP which clearly reflects increased BP variability (BPV) affects the survival of patients with heart failure (HF). The objective of the study was to investigate the relationship between the parameters specific to CHF severity and features of daily BP profiles in patients with ischemic CHF and hypertension. Methods: Ninety patients with functional class II–IV of CHF and CHD (the main group) and 50 non-CHF patients with hypertension (the comparative group) were examined. The transthoracic echocardiography (TTE) [atrial end-systolic dimension (ESD), ventricular end-diastolic dimension (EDD), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF)] and 24-hour ABPM (BPV parameters and proportions of hypotensive episodes) were performed. The relationships between the abovementioned parameters were evaluated using the univariate correlation analysis and stepwise multiple linear regression. Results: Higher functional class of CHF is found to be associated with a higher incidence of daytime systolic BP (SBP) decline and nighttime SBP and diastolic BP (DBP) variability while higher LVEF is related to the hypotensive episodes regardless of CHF. Conclusions: It appears that the larger trials involving CHF patients with reduced LVEF should be conducted to clarify the obtained results. Original Article Thu, 29 Feb 2024 00:00:00 GMT Natalia S.Akimova, Yury G.Shvarts, Nadezhda D.Mikhel, Anton R.Kiselev, Tatiana Y.Ledvanova, Larisa E.Konshina, Oksana V.Bugaeva, Thu, 29 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001209 https://www.explorationpub.com/Journals/em/Article/1001210 Aim: This study aimed to evaluate the role of chest radiographs and electrocardiograms in predicting the hemodynamics of congenital heart disease (CHD). Methods: This retrospective study included 50 patients with a diagnosis of CHD who had undergone any form of cardiac intervention, either surgical or nonsurgical between September 2019 and September 2020. Chest radiographs and electrocardiograms were evaluated and compared with the diagnostic gold standard echocardiography. Results: Chest radiographs had the highest sensitivity, specificity, and accuracy, with all being 100%, in detecting situs and cardiac position. There was a very good agreement between chest radiographs and echocardiography in the detection of both situs and cardiac position (κ = 1.00, P < 0.001), while moderate agreement was observed for the detection of cardiomegaly, position of the aortic knuckle, main pulmonary artery dilation, and right pulmonary artery dilation. Electrocardiograms had a high sensitivity (100.00%), but modest specificity and accuracy for the detection of left ventricle pressure overload. For the detection of left atrial enlargement and left ventricle volume overload, electrocardiograms had high specificity (94.12% and 94.29%, respectively) but low sensitivity and modest accuracy. There was a moderate agreement between electrocardiograms and echocardiography in the detection of right ventricle pressure overload (κ = 0.43, P = 0.002) and left ventricle volume overload (κ = 0.46, P < 0.001). Conclusions: The study findings indicate that chest radiographs and electrocardiograms alone are not adequate for the assessment of hemodynamics of CHD and reinstates the recommendation that in addition to routine chest radiographs and electrocardiograms, echocardiography should be performed. Original Article Thu, 29 Feb 2024 00:00:00 GMT RomilaChimoriya, GauravKumar, KritikaRana, RiteshChimoriya, ReenaAnand, Kulbhusan S.Dagar, NeerajAwasthy, Thu, 29 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001210 https://www.explorationpub.com/Journals/em/Article/1001211 Dry eye disease (DED) is a complex and multifactorial ocular surface disease affecting a large proportion of the population. There is emerging evidence of the impact of the microbiomes of the ocular surface and gut on the symptoms of DED, with many parallels being drawn to inflammatory diseases of other organ systems. A key factor involved in the promotion of healthy microbiomes, and which has been associated with ocular surface disease, is micro- and macronutrient deficiency. A comprehensive review of how these deficiencies can contribute to DED is absent from the literature. This review reports the composition of healthy ocular and gut microbiomes, and how nutrient deficiencies may impact these floral populations, with linkage to the subsequent impact on ocular health. The review highlights that vitamin B1 and iron are linked to reduced levels of butyrate, a fatty acid implicated in inflammatory conditions such as ulcerative colitis which itself is a condition known to be associated with ocular surface diseases. Vitamin B12 has been shown to have a role in maintaining gut microbial eubiosis and has been linked to the severity of dry eye symptoms. Similar beneficial effects of gut microbial eubiosis were noted with vitamin A and omega-3 polyunsaturated fatty acids. Selenium and calcium have complex interactions with the gut microbiome and have both been implicated in the development of thyroid orbitopathy. Further, diabetes mellitus is associated with ocular surface diseases and changes in the ocular microbiome. A better understanding of how changes in both the gut and eye microbiome impact DED could allow for an improved understanding of DED pathophysiology and the development of new, effective treatment strategies. Review Thu, 29 Feb 2024 00:00:00 GMT MadelinePilkington, DeclanLloyd, BradGuo, Stephanie L.Watson, Kenneth Gek-JinOoi, Thu, 29 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001211 https://www.explorationpub.com/Journals/em/Article/1001213 Over the past few decades, it has become clear that an excessive activity of matrix metalloproteinases (MMPs) can accelerate the progression and fatal outcomes of several serious age-related diseases, including atherosclerotic coronary heart disorders and various types of malignancies. These proteolytic enzymes mediate the degradation and remodeling of the extracellular matrix through cleaving its various components, thereby affecting many critical functions of surrounding cells and intercellular communication. Consequently, the low expression levels of MMPs can be important in the prevention and treatment of such chronic life-threatening pathologies, contributing to the better quality of life and longer life expectancy. In this review article, the pathogenic proteolytic roles of MMPs are examined in more detail, especially in the cases of heart attack and stroke as well as cancer invasion and metastasis, showing that these enzymes can be considered not only as diagnostic and prognostic biomarkers but also as important therapeutic targets in the fight against many age- and lifestyle-related serious disorders. The identification and development of suppressing agents with a selective activity towards specific MMPs have, however, still remained a complex and complicated challenge, in which natural plant-derived compounds are increasingly recognized as promising leads for the new-generation inhibitors. Review Mon, 08 Apr 2024 00:00:00 GMT KatrinSak, Mon, 08 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001213 https://www.explorationpub.com/Journals/em/Article/1001212 Aim: Transforming growth factor beta (TGF-β) receptor II (TGFBR2) is a basic constituent of TGF-β signalling pathway and is important in heart development. This study investigates the relationship between TGFBR2 gene variance and congenital heart defects (CHD) among Egyptians. Methods: The study involved 75 CHD-affected subjects and 100 healthy controls. Genotyping of two selected tag single nucleotide polymorphisms (tagSNPs, rs6785358, rs764522) within the TGFBR2 gene was conducted using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) assays. Results: Significant genotype differences were found for rs764522 and rs6785358 (P < 0.05). In the case of rs6785358, the G/G genotype was more prevalent in cases than controls (18.7% vs. 4.0%). This significance was observed in both the codominant model [A/A vs. A/G vs. G/G; odds ratio (OR) = 0.20, 95% confidence interval (CI) = 0.06–0.66, P = 0.0073] and the recessive model (A/A + A/G vs. G/G; OR = 0.19, 95% CI = 0.06–0.60, P = 0.0018). For rs764522, the G/G genotype was more prevalent in cases than controls (21.3% vs. 0.0%). Significant associations were observed in the codominant model (C/C vs. C/G vs. G/G; OR = 0.43, 95% CI = 0.02–0.90, P < 0.0001), as well as in the dominant model (C/C vs. C/G + G/G) and recessive model (C/C + C/G vs. G/G; P < 0.0001). Gender-specific analysis indicated that the C/G genotype was less common in male cases compared to females and controls (OR = 0.24, 95% CI = 0.07–0.84). For rs6785358, the G/G genotype frequency was higher in male cases compared to females and controls (OR = 0.10, 95% CI = 0.01–0.88 and OR = 0.22, 95% CI = 0.05–0.94, respectively). Conclusions: These findings indicate that TGFBR2 gene SNPs (rs6785358 and rs764522) may be risk factors for CHD in Egyptians. Original Article Fri, 29 Mar 2024 00:00:00 GMT NahedDawood, El-ShaimaaShabana, Ashraf A.H.El-Midany, Faten R.Abdelghaffar, IslamEl-Garawani, RizkElbaz, Fri, 29 Mar 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001212 https://www.explorationpub.com/Journals/em/Article/1001214 The dynamic of the virus-host interaction is subject to constant evolution, which makes it difficult to predict when the SARS-CoV-2 pandemic will become endemic. Vaccines in conjunction with efforts around masking and social distancing have reduced SARS-CoV-2 infection rates, however, there are still significant challenges to contend with before the pandemic shifts to endemic, such as the coronavirus acquiring mutations that allow the virus to dodge the immunity acquired by hosts. SARS-CoV-2 variants deploy convergent evolutionary mechanisms to sharpen their ability to impede the host’s innate immune response. The continued emergence of variants and sub-variants poses a significant hurdle to reaching endemicity. This underscores the importance of continued public health measures to control SARS-CoV-2 transmission and the need to develop better second-generation vaccines and effective treatments that would tackle current and future variants. We hypothesize that the hosts’ immunity to the virus is also evolving, which is likely to abet the process of reaching endemicity. Review Tue, 09 Apr 2024 00:00:00 GMT AzizulHaque, Anudeep B.Pant, Tue, 09 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001214 https://www.explorationpub.com/Journals/em/Article/1001215 Aim: It is unclear if individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with family histories of ME/CFS differ from those with ME/CFS without this family history. To explore this issue, quantitative data from patients with ME/CFS and controls were collected, and we examined those with and without family histories of ME/CFS. Methods: The samples included 400 patients with ME/CFS, and a non-ME/CFS chronic illness control group of 241 patients with multiple sclerosis (MS) and 173 with post-polio syndrome (PPS). Results: Confirming findings from prior studies, those with ME/CFS were more likely to have family members with ME/CFS than controls. We found family histories of ME/CFS were significantly higher (18%) among the ME/CFS group than the non-ME/CFS controls (3.9%). In addition, patients with ME/CFS who had family histories of ME/CFS were more likely to have gastrointestinal symptoms than those with ME/CFS without those family histories. Conclusions: Given the recent reports of gastrointestinal difficulties among those with ME/CFS, our findings might represent one predisposing factor for the emergence of ME/CFS. Original Article Fri, 12 Apr 2024 00:00:00 GMT Leonard A.Jason, SarahNgonmedje, Fri, 12 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001215 https://www.explorationpub.com/Journals/em/Article/1001216 Aim: Endothelial dysfunction has been associated with both cerebrovascular pathology and Alzheimer’s disease (AD). However, the connection between circulating endothelial cells and the risk of AD remains uncertain. The objective was to leverage data from the Framingham Heart Study to investigate various circulating endothelial subtypes and their potential correlations with the risk of AD. Methods: The study conducted data analyses using Cox proportional hazard regression and linear regression methods. Additionally, genome-wide association study (GWAS) was carried out to further explore the data. Results: Among the eleven distinct circulating endothelial subtypes, only circulating endothelial progenitor cells (EPCs) expressing CD34+CD133+ were found to be negatively and dose-dependently associated with reduced AD risk. This association persisted even after adjusting for age, sex, years of education, apolipoprotein E (APOE) ε4 status, and various vascular diseases. Particularly noteworthy was the significant association observed in individuals with hypertension and cerebral microbleeds. Consistently, positive associations were identified between CD34+CD133+ EPCs and specific brain regions, such as higher proportions of circulating CD34+CD133+ cells correlating with increased volumes of white matter and the hippocampus. Additionally, a GWAS study unveiled that CD34+CD133+ cells influenced AD risk specifically in individuals with homozygous genotypes for variants in two stem cell-related genes: kirre like nephrin family adhesion molecule 3 (KIRREL3, rs580382 CC and rs4144611 TT) and exocyst complex component 6B (EXOC6B, rs61619102 CC). Conclusions: The findings suggest that circulating CD34+CD133+ EPCs possess a protective effect and may offer a new therapeutic avenue for AD, especially in individuals with vascular pathology and those carrying specific genotypes of KIRREL3 and EXOC6B genes. Original Article Fri, 12 Apr 2024 00:00:00 GMT YixuanWang, JinghanHuang, Ting Fang AlvinAng, YiboZhu, QiushanTao, JesseMez, MichaelAlosco, Gerald V.Denis, AnnaBelkina, AshitaGurnani, MarkRoss, BinGong, JingyanHan, Kathryn L.Lunetta, Thor D.Stein, RhodaAu, Lindsay A.Farrer, XiaolingZhang, Wei QiaoQiu, Fri, 12 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001216 https://www.explorationpub.com/Journals/em/Article/1001217 Bacteriophages are viruses that infect bacterial cells and use their machinery to reproduce. This unique characteristic holds immense promise for combating antibiotic-resistant bacterial infections, a growing global threat. There are two types: one of them is named temperate phages, which inject their genomic material into bacteria and integrate into the host’s genome, while the second one is entitled as lytic phages that subdue the entire metabolism of the bacterium for the synthesis of its genome and proteins, including lytic proteins involved in breaking bacterial cell membrane and release of novel phages. In addition, phage therapy can be expressed through anti-biofilm activity and by triggering innate and adaptive immune cells responses. Moreover, no adverse effects of phage therapy have been reported. However, phage therapy is still grim for many and could influence some interpretations related to immune response, bacteriophage selections, and phage resistance in the future. Review Tue, 23 Apr 2024 00:00:00 GMT IsraNoor, Muhammad HassanNasir, AneeqUr Rehman, NoofJaved, WardaWaheed, AreebaWaheed, IshmalJamil, WajeehaShafiq, MuhammadHaseeb, Divya DhawalBhandari, HiteshChopra, Ahmad SyibliOthman, Tue, 23 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001217 https://www.explorationpub.com/Journals/em/Article/1001218 Aim: Hypoglycemia occurs in the neonatal period but the exact pathophysiology of the resulting brain injury at the cellular level is not well known. Therefore, a neonatal murine model was developed with insulin-induced hypoglycemia, to analyze the in-vitro effects of hypoglycemia on brain nucleotides and adenylate energy charge (AEC) throughout the first ten days of life. Methods: Newly born BALB/c pups between one and ten days of age were used. In each age group, six pups were subjected to insulin-induced hypoglycemia and six others served as controls. In both groups, immediately after euthanasia, brain tissues were collected. The in-vitro effects of hypoglycemia on brain nucleotides [adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP)] were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) as well on AEC. Results: In the controls, the cellular AEC steadily decreased with age by at least 50% over the 10-day study period (P < 0.05) except in the parietal tissue (P = 0.30) where it remained stable throughout that period. The most marked decrease was observed in the occipital tissue (P < 0.001). In the hypoglycemic mice, AEC in both the parietal and occipital tissues decreased significantly more than in the controls, more rapidly and pronounced between day 2 and 5 in the occipital tissue, reaching very low levels from day 5 onward. Except in the occipital tissue, none of the adenine nucleotides on its own, including ATP, reflected the cellular AEC. Conclusions: Over the first ten days of life, hypoglycemia progressively depleted cellular AEC in the brain, unlike cellular ATP concentration which did not appropriately reflect cellular energy. Original Article Tue, 23 Apr 2024 00:00:00 GMT HassibNarchi, PriyadharshiniYuvaraju, Junu A.George, Richard L.Jayaraj, RadhakrishnanSubramanian, Tue, 23 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001218 https://www.explorationpub.com/Journals/em/Article/1001219 Aim: The study was to evaluate the active matrix metalloproteinase-8 (aMMP-8) concentration in gingival crevicular fluid (GCF) and in peri-implant sulcular fluid (PISF) in healthy and diseased conditions, before and after non-surgical treatment, and to compare it with the various clinical parameters used to estimate the gingival and peri-implant inflammation. Methods: Plaque index/modified PI (PI/mPI), gingival index/simplified GI (GI/sGI), probing depth (PD), bleeding on probing index/modified BOPI (BOPI/mBOPI), radiographic bone loss/radiographic marginal bone loss (rBL/rMBL), and GCF/PISF samples were evaluated, before and 3 months after non-surgical treatment, GCF/PISF samples were analyzed by a chair-side mouth-rinse test (ImplantSafe®) in combination with a digital reader (ORALyzer®). Results: In all groups, aMMP-8 median levels were statistically higher in the PISF than in GCF and they did not change after treatment. Moreover, it was statistically higher in Group 3 (periodontitis/peri-implantitis) compared to the other groups. A positive correlation of the GCF/PISF and aMMP-8 median concentration was seen with increasing PD and BOPI/mBOPI values. A higher covariation of aMMP-8 mean levels in GCF with PD was found when compared to PISF levels. aMMP-8 mean levels in PISF expressed a higher covariation with increasing grades of sGI, rMBL, and BOPI while aMMP-8 GCF concentration established a better covariation with PD and PI. Conclusions: PISF of sites with peri-implant mucositis and peri-implantitis showed higher levels of aMMP-8 compared to sites with gingivitis and periodontitis. Compared to clinical indices, aMMP-8 concentration in GCF/PISF can be a beneficial adjunctive diagnostic tool for early identification and screening of the risk of peri-implant diseases. After non-surgical therapy, PISF aMMP-8 concentration remained mostly unchanged, while the GCF concentration of aMMP-8 significantly decreased. Original Article Tue, 23 Apr 2024 00:00:00 GMT RenzoGuarnieri, RodolfoReda, AlessioZanza, EditXhajanka, ShankargoudaPatil, DarioDi Nardo, LucaTestarelli, Tue, 23 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001219 https://www.explorationpub.com/Journals/em/Article/1001220 In this review, we present the main luminal fuels that are responsible for energy production in colonocytes, namely the bacterial metabolites short-chain fatty acids and lactate, which are produced from undigestible polysaccharides and proteins, and hydrogen sulfide that is mainly produced from undigested proteins. In addition to these luminal fuels, colonocytes can use glutamine, and to a lower extent glucose, as energy substrates provided by arterial capillaries. The effects of excessive concentrations of bacterial metabolites within the colonic luminal fluid (including butyrate, hydrogen sulfide, p-cresol, indole derivatives, ammonia, 4-hydroxyphenylacetic acid, and acetaldehyde) on the mitochondrial energy metabolism in colonic epithelial cells and the consequences of altered ATP production on the colonic epithelium renewal and barrier function are detailed, as well as consequences for water and electrolyte absorption. The relationships between modifications of these latter processes and development of colitis are then discussed. Finally, several mechanisms that are considered as adaptive against deleterious effects of bacterial metabolites on colonic epithelial cell energy metabolism are presented. Review Wed, 24 Apr 2024 00:00:00 GMT MireilleAndriamihaja, FrançoisBlachier, Wed, 24 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001220 https://www.explorationpub.com/Journals/em/Article/1001221 Lung cancer remains a leading cause of cancer-related deaths globally, and a significant number of patients are ineligible for surgery, while chemoradiotherapy often shows limited efficacy, a systemic distribution, a low drug concentration at tumor sites, severe side effects, and the emergence of drug resistance. In this context, a nanodrug delivery system (NDDS) has emerged as a promising approach for lung cancer treatment, offering distinct advantages such as targeted delivery, responsiveness to the tumor microenvironment, site-specific release, and enhanced induction of apoptosis in cancer cells, ultimately leading to tumor growth inhibition or even elimination. This review aims to provide an overview of the physiological characteristics of lung cancer, highlight the limitations of conventional treatment methods, and extensively examine recent significant advancements in NDDS utilized for lung cancer therapy. The findings from this review lay the foundation for further development and optimization of NDDSs in the treatment of lung cancer. Review Thu, 25 Apr 2024 00:00:00 GMT ShiyingZhang, XiaLi, YangLiu, HuiLi, ZhiyueZhang, Thu, 25 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001221 https://www.explorationpub.com/Journals/em/Article/1001222 Mushrooms, due to their many medical, preventive, and nutraceutical purposes, as well as their reputation as a folk remedy, have long been an integral part of traditional cuisines. The therapeutic advantages of mushrooms may be attributed to their bioactive components, including polysaccharides (both low and high molecular weight), terpenoids, phenolic compounds, fatty acids, lectins, and glucans. The bioactive components have been discovered to possess various health advantages, including antibacterial, antifungal, anticancer, radical scavenging, cardiovascular, anti-hypercholesterolemia, and anti-diabetic effects. These effects have gained worldwide attention and stimulated interest in further investigating their potential applications. Functional foods have the dual purpose of serving as both nourishment and medication. They may assist in the management and prevention of health disorders that are not functioning optimally, as well as mitigate some adverse effects of life-threatening diseases. Further evaluation is necessary to fully understand the mechanisms via which mushrooms operate and improve their therapeutic properties. This review delves into the possible medicinal potential of mushrooms and the advantages they may provide to human health. Review Mon, 06 May 2024 00:00:00 GMT Mohd JavedNaim, Mon, 06 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001222 https://www.explorationpub.com/Journals/em/Article/1001223 During cellular stress, the master regulators of intrinsic self-death (apoptosis) are BCL-2 family proteins. The BCL-2 family proteins play a key role in apoptosis and are tightly regulated via other BCL-2 family proteins, non-BCL-2 protein suppressors, and epigenetic modifications. As the name implies, these proteins possess one or two of the four BCL-2 homology domains (BH1–BH4). According to their roles, they are classified as pro-apoptotic or pro-survival proteins. BH-3-only proteins possess a single BH3 domain and are specific/key effector proteins for intracellular death commitment, particularly in the context of cell survival and programmed cell death. This delicate interplay among the BCL-2 family members is essential for maintaining the primary hemostasis, or balance, of cell fate. The anti-apoptotic proteins, such as BCL-2 and BCL-XL, promote cell survival by inhibiting apoptosis. On the other hand, the pro-apoptotic proteins, such as BAX and BAK, drive apoptosis. It ensures that cells are able to respond appropriately to various internal and external signals, ultimately determining whether a cell survives or undergoes programmed cell death. Understanding and targeting this delicate balance is a promising avenue for developing therapeutic strategies to modulate cell fate and treat various diseases. The molecular pathogenesis of BCL-2 family proteins in blood disorders involves differential expression of these components resulting in the dysregulation of the pathway contributing to cell survival and resistance to apoptosis as observed in follicular lymphoma, diffuse large B-cell lymphoma, acute lymphoblastic leukemia, and acute myeloid leukemia. Such dysregulation is a major impediment to standard therapies and aids in chemo resistance. Studies show some promising clinical outcomes with antineoplastic agent venetoclax either as a monotherapy or in combination with other agents. This review discusses recent studies on the regulation of BCL-2 family proteins which might provide a molecular landscape for their clinical implications in blood disorders. Review Sat, 11 May 2024 00:00:00 GMT FarisTayeb, Sat, 11 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001223 https://www.explorationpub.com/Journals/em/Article/1001224 Therapy of malignant tumors still represents a huge problem for healthcare, since these diseases lead to a high rate of disability and premature death of the population. The main problems of adoptive cell therapy for malignant tumors are a low rate of migration of effector lymphocytes into tumors, as well as their low activity in tumors due to suppressive tumor microenvironment. In addition, it should be noted that systemic intravenous administration of a large number of activated lymphocytes may be accompanied by a pronounced cytokine release syndrome, which leads to significant negative side effects, including high temperature, blood clotting disorders, aggression of immune cells against their own tissues, even neurotoxicity. Functional nanomaterials, such as magnetic nanoparticles with various surface modifications (PEG, PEI, DMSA, citrate, etc.) are highly promising agents for targeted delivery of different anti-tumor substances. Magnet-driven enrichment of effector anti-tumor lymphocytes in tumors would highly increase the effectiveness and enhance safety of adoptive lymphocyte therapy. However, different research groups obtained opposing data about the feasibility and efficiency of such approach. Thus, this review is focused on experimental details of the contradicting studies and aims to elucidate the possible reasons of these controversies and the best practices to efficiently target lymphocytes into tumors. Review Thu, 16 May 2024 00:00:00 GMT IrinaChikileva, PolinaFedorova, IrinaShubina, StanislavPshenichnikov, KaterynaLevada, VyacheslavAbramov, MikhailKiselevskiy, Thu, 16 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001224 https://www.explorationpub.com/Journals/em/Article/1001225 Excessive exposure to ultraviolet (UV) radiation causes premature aging of the skin, known as photoaging. UV radiation induces DNA damage, oxidative stress, inflammatory reactions, and degradation of extracellular matrix (ECM) proteins, contributing to the aged skin phenotype. The skin synthesizes vitamin D upon UVB exposure, which plays a pivotal role in the proper function of multiple body systems. Vitamin D protects skin from photo-damage by repairing cyclobutane pyrimidine dimers, reversing oxidative stress, and reducing chronic inflammation. Moreover, various epidemiological studies have identified vitamin D deficiency as a marker for common dermatological disorders. Improvement of clinical outcomes with vitamin D supplementation further suggests its protective role against skin pathologies. This review comprehensively covers the involvement of vitamin D in combating UV-induced photoaging and various skin disorders, highlighting the significance of maintaining vitamin D adequacy for healthy skin. Review Mon, 20 May 2024 00:00:00 GMT Sankalya S.Ambagaspitiya, Gayan A.Appuhamillage, Rohan S.Dassanayake, Mon, 20 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001225 https://www.explorationpub.com/Journals/em/Article/1001226 This article provides an informative overview of the current situation and future trends in cervical cancer prevention. Cervical cancer remains a significant public health concern worldwide and is characterized by notable variations in both incidence and mortality rates between developed and developing countries. This underscores the importance of understanding the pathophysiology of cervical cancer, stressing the involvement of high-risk HPV types. The presence of supplementary risk factors facilitates the transition from infection to cancer. This review examines current preventive methods, including the success of HPV vaccines such as Gardasil and Cervarix, and the effectiveness of screening techniques, from cytology to HPV DNA testing. It noted the limitations faced by primary and secondary preventive measures, particularly in low-resource settings, which include access to vaccines and effective screening procedures. Emerging technologies in cervical cancer prevention, such as liquid-based cytology, molecular testing, and AI, promise to improve early detection and diagnosis accuracy and efficiency. The potential of precision medicine to customize treatment based on individual risk factors was discussed. It explores the innovation in genetic editing techniques, such as CRISPR/Cas9, in targeting HPV oncoproteins, the advent of immunotherapy, the role of tumor-infiltrating lymphocytes, and the prospects of biomarkers in improving early detection. Research and technological advancements are leading to transformative changes in cervical cancer prevention. These developments suggest a path toward improved screening, diagnosis, and treatment that could significantly reduce the global burden of the disease. However, realizing the full potential of these advances requires inclusive research and international collaboration to overcome access disparities, particularly in resource-limited settings. Review Thu, 23 May 2024 00:00:00 GMT Praveen KumarChandra Sekar, Sheena MariamThomas, RamakrishnanVeerabathiran, Thu, 23 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001226 https://www.explorationpub.com/Journals/em/Article/1001227 Aim: The present study investigated whether commonly used screening tools and assessments for dementia were culturally appropriate for older adults from ethnic minorities (EM) groups living in the UK. Methods: Both South Asian and British participants (N = 43) were assessed using the Cross-Linguistic Naming Test, Mini Addenbrooke’s Cognitive Examination, Visual Short-Term Memory Binding Test (VSTMBT), and the Rowland Universal Dementia Assessment Scale. Multi-Ethnic Acculturation Scale and English proficiency, measured with a self-rated scale, were associated with the four respective. No interpreters were used. Results: While members from EM significantly differed from members of the ethnic majority group in traditional neuropsychological tasks, their performance on the VSTMBT yielded results comparable to those drawn from the ethnic majority group. Complex influences seem to drive the sensitivity of traditional neuropsychological tasks to sociocultural factors. Conclusions: This is the first study that subjects the VSTMBT to investigation in EM groups. Older adults from EM showed no impact of their sociocultural backgrounds on the function assessed by this test. However, other tests widely used for the assessment of EM populations proved sensitive to the investigated sociocultural factors. Our results lend support to the suggestion that neuropsychological assessments must abandon the one-size-fits-all notion when it comes to dementia risk detection among EM groups. Original Article Thu, 06 Jun 2024 00:00:00 GMT ClaraCalia, Mario A.Parra, Thu, 06 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001227 https://www.explorationpub.com/Journals/em/Article/1001228 Aim: Aloysia citrodora has a long history of traditional use in treating various ailments. This study evaluated the in vivo chemopreventive efficacy and systemic toxicity of an extract of A. citrodora in a transgenic mouse model of HPV16 (human papillomavirus type 16)-induced cancer. Methods: The experiment involved six groups (n = 5): group 1 (G1, wild-type (WT), water), group 2 (G2, HPV, water), group 3 (G3, WT, 0.013 g/mL), group 4 (G4, HPV, 0.006 g/mL), group 5 (G5, HPV, 0.008 g/mL), and group 6 (G6, HPV, 0.013 g/mL). Throughout the assay, humane endpoints, body weight, food, and water consumption were recorded weekly. The internal organs and skin of the mice were collected for analysis after they were sacrificed. Toxicological parameters that were studied included hematological and biochemical blood markers, splenic and hepatic histology, and hepatic oxidative stress. Results: A. citrodora extract seems to reduce the incidence of dysplastic and in situ carcinoma skin lesions induced by HPV16 in this model, suggesting that dietary supplementation with concentrations of 0.008 g/mL and 0.013 g/mL may have beneficial chemopreventive effects. Conclusions: The extract did not induce any concentration-dependent toxicological effects on any of the parameters included in the study, indicating a favorable toxicological profile under these experimental conditions. Original Article Wed, 19 Jun 2024 00:00:00 GMT BeatrizMedeiros-Fonseca, Ana I.Faustino-Rocha, JéssicaSilva, Mónica G.Silva, Maria JoãoPires, Maria JoãoNeuparth, HelenaVala, CármenVasconcelos-Nóbrega, Maria I.Dias, LillianBarros, LioGonçalves, IsabelGaivão, Margarida M. S. M.Bastos, LuísFélix, CarlosVenâncio, RuiMedeiros, Rui M. Gil daCosta, Paula A.Oliveira, Wed, 19 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001228 https://www.explorationpub.com/Journals/em/Article/1001229 Aim: This study investigates the collaborative efforts between speech language therapists and dentists to address the challenges faced by patients with concurrent dental and speech issues. It underscores the importance of understanding the complex interactions within the craniofacial system and its implications for both oral health and communication abilities. Methods: A questionnaire-based research was conducted involving speech language therapists and dentists, using Google Forms as the medium of data collection. This study was disseminated through professional networks, where practitioners provided information on their demographics, practices of collaboration, and the perceived advantages of such interdisciplinary work. All ethical standards were adhered to, ensuring the confidentiality and informed consent of the participants. Results: The findings indicate that dentists, often see first patient visits beyond recommended ages primarily for existing conditions, deviating from preventive norms. About half communicate monthly with speech language therapists, revealing gaps in early care and collaboration. Speech language therapists focus on language disorders and orofacial myofunctional disorders (SMOF), with 37% collaborating frequently with dentists. This interaction highlights the potential for enhanced patient outcomes through interdisciplinary cooperation. Despite these challenges, both groups acknowledged the benefits of their collaborative efforts. Conclusions: The partnership between speech language therapists and dentists represents a vital area of healthcare, aimed at tackling the complex issues of oral health and communication through a multidisciplinary approach. Although obstacles in collaboration were identified, the positive outcomes observed from such partnerships emphasize the importance of developing a unified framework to improve integrated healthcare delivery in the future. Original Article Tue, 25 Jun 2024 00:00:00 GMT MartinaCostanzo, FrancescoPuleio, RobertoLo Giudice, AngelaAlibrandi, IleniaCampione, Tue, 25 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001229 https://www.explorationpub.com/Journals/em/Article/1001230 Postbiotics, representing the newest member of the family of biotics, are metabolites produced as a result of fermentation of lactic acid bacteria (LAB) in the De Man, Rogosa, and Sharpe (MRS) medium which includes proteins, sugars and minerals. The components of postbiotics includes exopolysaccharides (EPS), short-chain fatty acids (SCFAs), bacteriocins, antioxidants, and metabolizing enzymes. Several studies indicate that postbiotics have multiple properties such as antimicrobial, immunomodulatory, antioxidant, anti-inflammatory, anti-obesity, anti-diabetic, and anti-tumoral properties. Natural polysaccharides refer to the polysaccharides obtained from biological organisms including algae, plants, animals, and microorganisms. Polysaccharides are either branched or linear macromolecules and are composed of a few major and some minor monosaccharides, including glucose, fructose, mannose, arabinose, galactose, fucose, galacturonic acid, glucosamine, galactosamine or their derivatives. Similar to postbiotics, polysaccharides also exhibit anti-inflammatory, antibacterial, antitumor, antiviral, immunomodulatory, and antioxidant properties. Although polysaccharides cannot be directly digested by the human body due to the lack of specific enzymes, they can be digested by gut-residing bacteria including but not limited to LAB. Recent studies indicate that large non-starch polysaccharides such as alginate, fucoidan, chitosan, carrageenan, and guar gum can be degraded into low molecular weight oligosaccharides which in turn can provide health benefits to the human health. These new findings inspired us to propose a polysaccharides-based postbiotics, also called glycanbiotics, and their potential applications. We propose that polysaccharides can be fermented by probiotics, and subsequent removal of bacteria will increase the safety of their produced metabolites, including oligosaccharides, disaccharides, monosaccharides and their derivatives. These polysaccharides-based postbiotics may mimic metabolization of polysaccharides in vitro and consequently broaden the applications of postbiotics. Non-probiotics such as Akkermansia muciniphila and other bacteria can also be used for glycanbiotics production, thus providing novel applications for human health. Review Fri, 28 Jun 2024 00:00:00 GMT WeinanDu, LucaDi Martino, JuxiuLi, Fri, 28 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001230 https://www.explorationpub.com/Journals/em/Article/1001231 The integration of digital technologies like CAD/CAM systems and intraoral scanners is transforming the field of dentistry, providing numerous benefits for both patients and dental professionals. This case study explores the significance and benefits of dental CAD/CAM technology in revolutionizing the dental industry, focusing on the creation of personalized dental restorations with precision and speed. The study emphasizes the applications of CAD/CAM technology and showcases the state-of-the-art Medit i700 intraoral scanner for detailed dental impression scanning. By adopting these advanced technologies, dental practices can save time, enhance patient satisfaction, and reduce costs in the long run. The methodology involved systematic digital assessments, planning, and execution to address cosmetic concerns, resulting in a successful transformation of a patient’s smile using e.max® CAD/CAM technology and Medit i700 scanner. The case study highlights the importance of patient preference, efficiency, and accuracy in digital dentistry, demonstrating the potential for providing personalized and effective solutions for aesthetic dental concerns. Embracing digital advancements and patient-centered care is crucial for delivering high-quality and innovative solutions in modern aesthetic dentistry. Case Report Fri, 28 Jun 2024 00:00:00 GMT ZeinaDarwich, AtefDarwich, MarwanAl-Raeei, ChadiAzmeh, Fri, 28 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001231 https://www.explorationpub.com/Journals/em/Article/1001232 Aim: Magnetodynamic surgery has assumed increasing importance in recent years. The purpose of the present study was to compare in vitro, using dry porcine ribs, two methods of dental implant site preparation (conventional drill and magnetic mallet) on three aspects of the site. These were the difference between the diameter of the site and the diameter of the last drill used (an index of the accuracy of the preparation), the weight loss of the specimen on which the site was prepared (index of the bone loss in the site), and the change of temperature at the site (an index of the change to the material at the site). Methods: Eight preformed pork ribs were chosen for the study. Four implant preparations were made on each rib, two with Magnetic Mallet (Meta Ergonomica, Turbigo, Italy) and two with traditional drills. Each bone sample was weighed before and after implant site preparation in order to calculate the amount of bone lost during preparation. The diameter of preparations was analyzed with the aid of an optical microscope (MZ6, Leica, Wetzlar, Germany) connected to a dedicated measurement software. For the evaluation of the temperature, eight preparation sites were marked. In correspondence of each preparation site, on the opposite side of the rib, a hole was made for the thermocouple (HI 91530K, Hanna Instruments, Padova, Italy). During the preparations, the thermocouple was kept inserted inside the control hole to record the temperature variation. The results were analyzed using appropriate statistical methods, such as the Kolmogorov-Smirnoff test and the Wilcoxon test. Results: It was found that mallet drill provided significantly higher accuracy of preparation, lower amount of damage at the site, and less change to the porcine rib test material at the preparation site. Conclusions: A possible clinical implication of this finding is discussed. Original Article Fri, 05 Jul 2024 00:00:00 GMT DomenicoBaldi, Jason MottaJones, EnricoLertora, ChiaraBurgio, Andrea TancrediLugas, GianmarioSchierano, JacopoColombo, Fri, 05 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001232 https://www.explorationpub.com/Journals/em/Article/1001233 Background: This systematic review aims to critically assess the literature on the debonding process of orthodontic brackets from enamel surfaces. The review evaluates Randomized Controlled Trials (RCTs) to determine the effectiveness and implications of various debonding techniques and materials. Methods: The study followed PRISMA guidelines, selecting RCTs published from 1999 onwards that compared the outcomes of various orthodontic bracket debonding techniques. Selection criteria included studies utilizing human teeth, with outcomes such as enamel surface roughness and Adhesive Remnant Index (ARI) analyzed. Data sources included PubMed, Scopus, Web of Science, and the Cochrane Library. Results: Out of 1,587 records identified, five studies met the inclusion criteria. These studies provided comparative data on the effectiveness of various debonding techniques, including tungsten carbide and diamond burs, in minimizing enamel damage and optimizing adhesive removal. Findings indicated that tungsten carbide burs produced the least enamel roughness. Discussion: Utilizing tungsten carbide burs for debonding orthodontic brackets significantly minimizes enamel surface roughness and potential damage, thereby enhancing the preservation of enamel integrity post-treatment. The systematic review highlights current debonding techniques are effective in adhesive removal, and the choice of instrument significantly affects enamel integrity and clinical outcomes. The findings support the need for continuous improvement and innovation in removing braces to improve orthodontic treatment results and patient satisfaction. Systematic Review Fri, 05 Jul 2024 00:00:00 GMT FrancescaGorassini, LucaFiorillo, Maria MaddalenaMarrapodi, CesareD’Amico, MichelaBasile, MarcoCicciù, GabrieleCervino, Fri, 05 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001233 https://www.explorationpub.com/Journals/em/Article/1001234 Not applicable. Correction Thu, 11 Jul 2024 00:00:00 GMT DomenicoBaldi, Jason MottaJones, EnricoLertora, ChiaraBurgio, Andrea TancrediLugas, GianmarioSchierano, JacopoColombo, Thu, 11 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001234 https://www.explorationpub.com/Journals/em/Article/1001235 Background: The naturally occurring metabolite lactate has traditionally been considered as a waste product of anaerobic metabolism whose production was confined to hypoxic states. However, more evidence supports that lactate is a preferred oxidative substrate for the myocardium when present in high plasma levels. Small-scale clinical studies have found that infusion of exogenous hypertonic sodium lactate (HSL) increases cardiac output and stabilizes the haemodynamic profile. More comprehensive studies investigating haemodynamic or cardiovascular effects of HSL have been conducted using different animal models of disease. Methods: We performed a broad systematic search of electronic databases PubMed and Embase to identify animal studies in which haemodynamic or cardiovascular effects of HSL were reported. A total of 135 studies were identified. Nineteen studies were included in this review. Different disease models were included including sepsis (n = 4 studies), cardiac arrest (n = 3 studies), myocardial infarction (n = 2 studies), haemorrhagic shock (n = 3 studies) while studies on healthy hearts (n = 4 studies) were included. Also, three studies investigating the cardioprotective and cardiometabolic roles of HSL were included. Results: The review explains several beneficial haemodynamic effects of HSL infusion during a variety of disease states including increased cardiac output, increased microcirculation, and decreased systemic inflammation. Only a few studies identified the negative effects of HSL infusion. This paper suggests that high doses of lactate serve as an important cardiac fuel during crises and can also function as a pH buffer. However, the review revealed significant flaws in the reporting quality of the majority of studies. Discussion: HSL infusion holds promise as a potential treatment fluid for a variety of diseases. Future translational studies should focus on enhancing reproducibility, study design, and study reporting. Systematic Review Thu, 11 Jul 2024 00:00:00 GMT Oskar KjærgaardHørsdal, Thu, 11 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001235 https://www.explorationpub.com/Journals/em/Article/1001236 The emergence and subsequent advancement of nanotechnology in recent years have greatly benefited the healthcare sector, particularly in the treatment of cancer. As per study, major fatalities are related to the lung cancer. For many years, oral tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor (EGFR) family of receptors have been used in the clinic to treat human malignancies, although they observed some very serious adverse effects in the treatment of lung cancer, especially in non-small cell lung cancer (NSCLC). Despite EGFR-TKIs’ exceptional qualities as small-molecule targeted medications, their applicability is nevertheless limited by their poor solubility, inconsistent oral bioavailability, high daily dose needs, high plasma albumin binding propensity, and initial/acquired drug resistance. Article’s purpose is to investigate EGFR-TKI’s effects on lung cancer and get around some of its drawbacks, nanotechnology will be an innovative strategy. An effective tool to increase the effectiveness of these pharmaceuticals is nanotechnology by methods other than oral. This article signifies that a range of nanomedicine delivery systems have been developed to effectively distribute EGFR-TKIs with improved drug release kinetics and tissue-targeting capacity. This review article intends to present information regarding lung cancer and EGFR relation, mechanism of recently approved EGFR-TKI’s targeted therapy, an updated landscape of EGFR-TKIs and their clinical status over lung cancer, advantages and disadvantages of nanotechnology, and new breakthroughs in nano-delivery which mentioned as a significantly better over traditional drug chemotherapy and delivery. Review Mon, 15 Jul 2024 00:00:00 GMT Priyanka S.Waghmare, Anuruddha R.Chabukswar, Kunal G.Raut, BhagyashreeGaikwad-Pawar, Swati C.Jagdale, Mon, 15 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001236 https://www.explorationpub.com/Journals/em/Article/1001237 Aim: Present study was done to understand the dimerization of HER2/ERBB2 in normal and cancer cells using in-silico study. Methods: Pathway analysis was done using Reactome. Structure of HER2/ERBB2 protein was obtained from PDB database, and using Schrödinger software protein structure was analysed and dimerization was done. Results: In normal cells, HER2/ERBB2 is present at low levels and forms a stable complex with HSP90 (heat shock protein 90), CDC37 (cell division cycle 37), and ERBIN (an adaptor protein of the HER2/ERBB2 receptor). HER2/ERBB2 lacks a ligand-binding site, so it cannot bind ligands to activate HER2/ERBB2 signaling directly. Instead, it heterodimerizes with other EGFR family members, using their ligand-binding sites to activate cell proliferation signaling cascades. In cancer, overexpression of HER2/ERBB2 leads to ligand-independent activation of signaling through dimerization. During this process, HER2/ERBB2 dissociates from the HSP90 complex. Normally, HSP90 helps to correct misfolded and aggregated proteins, but it fails to correct mutated HER2/ERBB2 in cancer cells. Conclusions: This discussion focuses on the structural changes that HER2/ERBB2 undergoes, particularly in the form of homodimers, under normal and cancerous conditions. This analysis highlights the mutated state of HER2/ERBB2 and the role of HSP90 in this context. Notably, a single-point mutation outside a protein’s active site can significantly alter its structure. This is a critical consideration in drug discovery, underscoring the need to evaluate the entire protein conformation during simulations. Original Article Wed, 17 Jul 2024 00:00:00 GMT JayasreeSanthanakrishnan, PrabhuMeganathan, HemamaliniVedagiri, Wed, 17 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001237 https://www.explorationpub.com/Journals/em/Article/1001239 Aim: Cervical squamous cell carcinoma (CESC) is a highly prevalent women’s gynecologic disease. Because the specific mechanisms associated with the illness are still mostly unclear, more investigation is needed to comprehend the triggers of CESC’s initiation and progression. Circular RNAs (circRNAs) are a new type of RNA that control microRNAs’ (miRNAs) expressions. Although particular circRNA–miRNA–mRNA regulatory axes for CESC have been defined, little is known about this field of research. Therefore, the current study aimed to identify new circRNA–miRNA–mRNA axes in CESC. Methods: GSE102686 and GSE169057 GEO datasets were utilized to identify differentially expressed circRNAs (DEcircRNAs). The Cancer Genome Atlas (TCGA) database was used to detect differentially expressed miRNAs (DEmiRs) and mRNAs (DEmRNAs). Various in silico tools were used to identify interactions between circRNAs, miRNAs, and their potential target genes in CESC. Moreover, enrichment analysis, correlation analysis, and survival analysis were performed on potential target genes. Results: Utilizing publically available data, we found dysregulated circRNAs, miRNAs, and mRNAs in CESC. We showed that the circRNA hsa_circ_0000711 may be involved in the CESC process by inhibiting many target genes via hsa-miR-338-3p and/or hsa-miR-361-3p. Moreover, we found that hsa_circ_0000515 circRNA can contribute to CESC by modulating the expression of some target genes via hsa-miR-296-5p. Conclusions: The findings of this work contribute to a better understanding of the circRNA–miRNA–mRNA regulation processes in CESC. Original Article Thu, 01 Aug 2024 00:00:00 GMT MuratKAYA, Thu, 01 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001239 https://www.explorationpub.com/Journals/em/Article/1001238 Diabetic ketoalkalosis (DKALK) is a rare but significant variant of diabetic emergencies, characterized by metabolic alkalosis rather than the typical acidosis seen in diabetic ketoacidosis (DKA). Despite its clinical importance, DKALK often goes unrecognized due to limited literature on its presentation and biochemical variables. This work examines the pathophysiology, clinical presentation, diagnostic challenges, management strategies, and implications for clinical practice of DKALK, drawing insights from case studies and research gaps in the field. Notable case studies underscore the diagnostic challenges and emphasize the importance of tailored management strategies for DKALK. Risk assessment involves recognizing predisposing factors such as severe vomiting, alcohol abuse, or concomitant diuretic use. Timely recognition and intervention are essential to prevent potentially life-threatening complications associated with DKALK. Continued research efforts are warranted to refine diagnostic criteria, optimize therapeutic approaches, and enhance early recognition of DKALK, ultimately improving patient outcomes in this challenging clinical scenario. Review Thu, 01 Aug 2024 00:00:00 GMT PatrickAshinze, NelsonMafua, SuvamBanerjee, EniolaObafemi, AkandeEniola, EgbunuEmmanuel, Akogwu OcholiEdache, Aremu SikiruAdemola, Chukwu BethrandOzioma, Peace NgoziOkoro, Thu, 01 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001238 https://www.explorationpub.com/Journals/em/Article/1001240 Aim: To evaluate the fracture resistance of printed crowns with two different designs. Methods: Forty restorations (n = 20/group) were fabricated using resin matrix ceramic (VarseoSmileTM) with different designs as follows: group 1: overlay restoration with chamfer margin; group 2: overlay restoration with chamfer margin located 3 mm above the gingiva. Restorations were bonded to resin dies using 3M RelyX Luting Cement. Compression forces were applied with a 4 mm diameter steel bar at the midline fissure of each crown using the universal testing machine. Restorations were loaded until fracture, and fracture resistance at maximum load was recorded. Statistical analysis: A t-test was used for statistical comparison between groups. Results: No difference in the fracture resistance was detected for both groups. Conclusions: Different designs of composite resin crowns fabricated using CAD/CAM techniques can be used, however further research is needed to assess the clinical outcomes. Original Article Thu, 01 Aug 2024 00:00:00 GMT SalwaMekled, MarkIskander, BelindaRodriguez, PaigeHodges, JasleenBhogal, JoanAdechoubou, GeraldineWeinstein, Thu, 01 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001240 https://www.explorationpub.com/Journals/em/Article/1001243 Autologous fat grafting is a common technique in cosmetic and reconstructive surgery, addressing facial rejuvenation, breast contouring, scar mitigation, and soft tissue corrections. However, clinical outcomes can be inconsistent and unpredictable. While extensive research has explored the mechanisms of harvesting, purifying, and transplanting adipose tissue, there is a notable gap in understanding the impact of donor-related factors on fat grafting success. This review aims to fill this gap by examining how variables like donor age, sex, health status, and anatomical site of fat harvest influence the biological efficacy of adipose-derived stem cells (ASCs). Younger donors often exhibit higher ASC proliferation rates and regenerative potential, while older donors may have reduced cell viability. Hormonal differences between sexes and donor health conditions, such as obesity or diabetes, can also impact ASC functionality and graft outcomes. The anatomical source of the fat further affects its cellular composition and regenerative potential. Understanding these donor-related factors is vital for optimizing fat grafting techniques. The review also explores innovative strategies, such as adipose tissue cryopreservation and acellular fat matrices, to mitigate donor variability. These approaches offer promising avenues for enhancing the predictability and effectiveness of fat grafting. By synthesizing current knowledge and highlighting novel strategies, this review aims to improve clinical outcomes and advance the field of aesthetic and reconstructive surgery. Review Fri, 11 Oct 2024 00:00:00 GMT OzalBeylerli, IlgizGareev, BoxianZhao, ElmarMusaev, Fri, 11 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001243 https://www.explorationpub.com/Journals/em/Article/1001241 Aim: This study provides a comparative analysis of oral dysbiosis of patients with periodontal diseases: chronic catarrhal gingivitis and generalized periodontitis, associated with various systemic pathologies, using a combination of the enzymatic method and interval scale. Studying the differences in the oral microbiota of patients with periodontal diseases and systemic pathologies can help comprehend the underlying mechanisms and create successful treatments. Methods: An enzymatic method was used to diagnose and monitor the degree of oral dysbiosis of patients with different systemic pathologies and periodontal diseases. We applied particular inclusion and exclusion criteria to include patients in a study. The level of microbial presence in the oral cavity can be measured by analyzing urease enzyme activity. Results: The research established that oral dysbiosis is observed in all groups of patients with periodontal diseases and systemic pathology: chronic colitis, chronic pancreatitis, and primary hypothyroidism. The article discusses an express method of diagnosing the microbiota of the oral cavity in combination with an interval scale. This combination makes it possible to classify patients according to the level of oral dysbiosis and prescribe further recommendations for treatment. Conclusions: The association of periodontitis and linked comorbidities is a complex interplay involving common risk factors, pathophysiology, and bidirectional causal relationships. The imbalance of microorganisms in the oral cavities of patients with systemic and periodontal diseases highlights the need for a personalized medical treatment approach. Correcting dysbiosis of the oral cavity should complement antimicrobial treatment for periodontal diseases and the normalization of metabolic processes in the periodontium. It has been confirmed that there is a correlation between patients’ microbial colonization of the oral cavity and the values obtained by the enzymatic method, suggesting that this approach can serve as a rapid assessment of the oral cavity’s microbiocenosis. Original Article Wed, 04 Sep 2024 00:00:00 GMT OlhaDenefil, SofiiaChorniy, SvitlanaBoitsaniuk, NataliaChornij, MarianaLevkiv, LiudmylaPatskan, KhrystynaPohoretska, NadiiaManashchuk, MartaZaliznyak, NataliaTverdokhlib, Wed, 04 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001241 https://www.explorationpub.com/Journals/em/Article/1001242 Harmattan is a season characterized by dust, cold, and sub-humid trade winds in Sub-Saharan countries. It’s similar to meteorological phenomena like Asian dust storms, Santa Ana winds, Australian bushfires, and Saharan dust in the Caribbean. It causes profound changes in the cardiorespiratory system in apparently healthy individuals and increases the risk of hospitalization in susceptible individuals. Exposure to these extreme conditions has been associated with alterations in autonomic function and baroreceptor sensitivity thus resulting in dysregulation of blood pressure control mechanisms. Baroreceptors are critical regulators of hemodynamics and cardiovascular function. They play a vital role in the short-term responses to blood pressure perturbation and are essential for acute restoration of blood pressure following cold exposure. Harmattan wind contains a barrage of chemicals, dust, and particulate matters depending on industrialization, natural and human activities. Particulate matter from Harmattan dust can trigger systemic inflammation and oxidative stress, exacerbating endothelial dysfunction and impairing vascular reactivity thus contributing to the pathogenesis of alterations in baroreceptor insensitivity, and cardiovascular diseases, including hypertension and atherosclerosis. Furthermore, fine particulate matter from dust may penetrate deep into the respiratory tract, activating pulmonary sensory receptors and eliciting reflex responses that influence autonomic tone. The presence of rich acrolein smokes and non-essential heavy metals such as cadmium, lead, and mercury in Harmattan wind also reduces baroreflex sensitivity, culminating in a sustained increase in diastolic and systolic blood pressure. This integrated review aims to provide valuable insights into how changes in each of these environmental constituents alter vital pathophysiologic and immunologic mechanisms of the body leading to baroreceptor instability and ultimately hemodynamic imbalance using available primary studies. Understanding this intricate interplay is crucial for implementing targeted interventions and informed public health strategies to mitigate the adverse effects of extreme environmental exposure and ultimately reduce poor health outcomes in the affected regions. Review Tue, 10 Sep 2024 00:00:00 GMT Mayowa JeremiahAdeniyi, Oyesanmi A.Fabunmi, AyoolaAwosika, Tue, 10 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001242 https://www.explorationpub.com/Journals/em/Article/1001244 Aim: Burning mouth syndrome (BMS) is a debilitating chronic burning sensation in the oral cavity with no identifiable cause. The present research was conducted to evaluate the prevalence profile of BMS in a sample of the Egyptian population. Methods: A cross-sectional study was performed by screening 952 subjects, all individuals with burning mouth complaints were interviewed and examined to identify the site, timing, frequency, and intensity of their burning sensations. The presence of associated xerostomia, taste disturbances, and impact on quality of life was also recorded. The extent of perceived stress was assessed using the short version of the Perceived Stress Scale. Results: Among the total 952 cases, 75 cases suffered from BMS symptoms representing a prevalence rate of 7.9%, occurring more frequently in females and those aged 50 years and older. Additionally, 86.7% of cases suffered from systemic diseases, most commonly, diabetes mellitus and hypertension, and were on long-term medications. The intensity of BMS symptoms was relatively high (7.81 ± 1.72). It was significantly correlated with age, smoking, duration of BMS, presence of medical conditions, long-term medications, quality of life, and Perceived Stress Scale scores. The most involved locations were the tongue and buccal mucosa. Xerostomia was reported in 78.7% of cases, while disturbance of taste sensation was reported in 49.3%. Conclusions: This is the first reported prevalence data for BMS in the Egyptian population in an attempt to improve the limited amount of relevant literature, revealing a BMS prevalence of 7.9% with a significant impact on the quality of life. Original Article Mon, 14 Oct 2024 00:00:00 GMT DaliaGhalwash, AsmaaAbou-Bakr, AhmedAmmar, AhmedHamdy, AymanEl-Gawish, Mon, 14 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001244 https://www.explorationpub.com/Journals/em/Article/1001245 Streptococcus pneumoniae (S. pneumoniae), which is a Gram-positive diplococcus, has emerged as a significant human pathogen. It is a primary cause of bacterial pneumonia, otitis media, meningitis, and septicemia, leading to a considerable impact on global morbidity and mortality. The investigation of S. pneumoniae and its virulence factors has resulted in the identification of surface endonuclease A (EndA). EndA functions in DNA uptake during natural transformation and plays a significant role in gene transfer. The ability of S. pneumoniae to degrade neutrophil extracellular traps (NETs) enhances its virulence and invasive potential in pneumococcal infections. NETosis occurs when neutrophils release chromatin into the extracellular space to form NETs, capturing and neutralizing pathogens. Currently, NETosis can be induced by several microbes, particulate matter, and sterile stimuli through distinct cellular mechanisms, and this includes the involvement of EndA in S. pneumoniae. Here, we reviewed the cellular functions of EndA, its role in S. pneumoniae as a virulence factor in relation to NETosis, its relationship to immunogenicity, and its involvement in several diseases. The discovery of this relationship would significantly impact therapeutic technology in reducing disease burden, especially pneumococcal infections. Review Mon, 14 Oct 2024 00:00:00 GMT MarinaYusoff, Chew ChiengYeo, Muhammad HassanNasir, MalikAmonov, Mon, 14 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001245 https://www.explorationpub.com/Journals/em/Article/1001246 Aim: The aim of this study is to investigate whether germline alterations of exon 5 of TP53 gene could be detected in the blood of known men with prostate cancer and to assess the potential association between the genomic alteration affecting this gene and clinicopathological characteristics of the patients. Methods: Forty-eight blood samples from men diagnosed with prostate cancer were analyzed for TP53 germline mutations and confirmed by Sanger sequencing. The frequency and distribution of high-frequency mutations were analyzed according to the pathological criteria of the patients and a computational study was performed to assess the effect of new mutations. Results: The Sanger sequencing revealed that 79% of the population studied carry mutations in TP53 gene. In summary, a total of 137 mutations have been identified in this gene, out of which 115 are new mutations. Frameshift mutations were the most frequent; the mutation c.392delA was recorded in fifteen cases (31%); the mutations c.383delC and c.432delG were observed at a frequency of 12.5% and 10% respectively. The most frequent missense mutation was the variant c.502C>A (p.His168Asn) identified in eleven patients (23%). One nonsense mutation was identified in one patient and resulted in a stop codon in position 126 (tyrosine). All codons affected by these alterations are part of the DNA binding domain of the protein TP53. Conclusions: The germline mutation frequency observed in prostate cancer patients, and the new mutations recorded in TP53 gene, could be in favor of a potential association of genomic alterations in this gene and prostate cancer genesis, thereby constituting a tool, similar to other genes in the DNA repair pathway such as BRCA1 and BRCA2. This could contribute to the advancement of diagnosis and therapeutic strategies for prostate cancer. Original Article Fri, 18 Oct 2024 00:00:00 GMT KawtarAboulalaa, AbdelilahLaraqui, RedaTagajdid, KhalidEnnibi, Moulay MustaphaEnnaji, Fri, 18 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001246 https://www.explorationpub.com/Journals/em/Article/1001247 Background: Post-endoscopic retrograde cholangiopancreatography acute pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Studies have shown that periprocedural administration of lactated Ringer’s (LR) solution may prevent PEP by multiple mechanisms. To assess the evidence for periprocedural aggressive hydration with LR alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs) as a preventive measure for post-ERCP pancreatitis, an updated systematic review was conducted. Methods: Thirteen randomized controlled trials (RCTs) were selected, including eight trials (a total of 2,095 patients) evaluating aggressive hydration with LR alone and five RCTs (a total of 1,550 patients) evaluating LR in combination with NSAIDs. A critical analysis of the data was conducted. Results: RCTs evaluating the use of LR as monoprophylaxis showed that patients in the LR arm had a significantly reduced likelihood of developing PEP compared with standard hydration or placebo, and no lower likelihood than with indomethacin. RCTs investigating combined prophylaxis initially showed increased efficacy compared with single prophylactic strategies, but this superiority was no longer confirmed in more recently published trials involving larger numbers of patients. Discussion: Aggressive hydration with LR is an effective alternative prophylactic strategy to NSAIDs for PEP. Further studies are needed to ascertain whether prophylaxis with a combination of aggressive hydration with LR and NSAIDs is more effective than prophylaxis with NSAIDs alone. Systematic Review Tue, 22 Oct 2024 00:00:00 GMT Vincenzo GiorgioMirante, AmedeoLonardo, SimoneGrillo, FrancescaFranzoni, RomanoSassatelli, Tue, 22 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001247 https://www.explorationpub.com/Journals/em/Article/1001248 Aim: Hypertension, a prevalent chronic condition, significantly contributes to cardiovascular diseases worldwide. Effective management of hypertension is highly dependent on patient adherence to prescribed medications, as the correct dose at the right time can lead to desirable therapeutic results. This study aims to analyze medication adherence among hypertensive patients in Islamabad and Rawalpindi through an open survey. Methods: A prospective cross-sectional study was conducted from 17th March 2024 to 30th May 2024, targeting hypertensive populations in Islamabad and Rawalpindi. 246 patients were recruited using a sample size formula, and a General Medication Adherence Scale (GMAS) questionnaire was used to collect data. All the tests were conducted as two-sided, with a significance level of P < 0.05 using Python. Results: Among 246 participants (mean age 57.1 years), most were married, literate, and living with families, 63% were from Islamabad, and 78.9% were employed. The study found high adherence in behavior-related areas but low adherence due to costs. Gender showed a statistically significant correlation (P = 0.03) by independent t-test. At the same time, ANOVA tests revealed that educational level (P = 0.02), monthly income (P = 0.001), family support (P = 0.04), and medication costs (P = 0.001) significantly impacted adherence, while factors like social status, employment status, and smoking did not have a considerable influence. Conclusions: 72.4% of patients adhered to their prescribed therapy, and 27.6% did not highlight a critical issue that requires urgent intervention. Variables like gender, educational status, social status, occupation, and living with family are strongly associated with adherence. Common problems include taking multiple medications, lack of awareness about the importance of adherence, and financial constraints. Original Article Wed, 23 Oct 2024 00:00:00 GMT SameenAbbas, MaidaNoor, Ahmad JalalMasood, EjazAhmed, AroobaShakeel, Muhammad SaadAli, UsamaRizwan, SohailKamran, Wed, 23 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001248 https://www.explorationpub.com/Journals/em/Article/1001249 Diabetic vascular disease, as one of the common complications in diabetic patients, threatens the quality of life and health of patients. Autophagy maintains cellular homeostasis and survival as an important intracellular self-repair mechanism. In recent years, with the gradual deepening of autophagy research, more and more studies have found that vascular cells such as endothelial cells, smooth muscle cells, and inflammatory cells are closely associated with various autophagy disorders. Different autophagy regulatory mechanisms can lead to different or similar cellular outcomes, and there are complex crosstalk mechanisms in the process. Therefore, we will summarize the latest research progresses with regards to the role of autophagy in diabetic vascular disease, focusing on the complex regulatory mechanisms of mitophagy, epigenetic modifications, apoptosis, inflammation, and autophagy in the development of diabetic vascular disease, aiming to provide effective therapeutic targets for diabetic vascular injury. Mini Review Fri, 25 Oct 2024 00:00:00 GMT YingAn, JunRen, Fri, 25 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001249 https://www.explorationpub.com/Journals/em/Article/1001250 Aim: Skin lesion segmentation is critical for early skin cancer detection. Challenges in automatic segmentation from dermoscopic images include variations in color, texture, and artifacts of indistinct lesion boundaries. This study aims to develop and evaluate MUCM-Net, a lightweight and efficient model for skin lesion segmentation, leveraging Mamba state-space models integrated with UCM-Net architecture optimized for mobile deployment and early skin cancer detection. Methods: MUCM-Net combines Convolutional Neural Networks (CNNs), multi-layer perceptions (MLPs), and Mamba elements into a hybrid feature learning module. Results: The model was trained and tested on the International Skin Imaging Collaboration (ISIC) 2017 and ISIC2018 datasets, consisting of 2,000 and 2,594 dermoscopic images, respectively. Critical metrics for evaluation included Dice Similarity Coefficient (DSC), sensitivity (SE), specificity (SP), and accuracy (ACC). The model’s computational efficiency was also assessed by measuring Giga Floating-point Operations Per Second (GFLOPS) and the number of parameters. MUCM-Net demonstrated superior performance in skin lesion segmentation with an average DSC of 0.91 on the ISIC2017 dataset and 0.89 on the ISIC2018 dataset, outperforming existing models. It achieved high SE (0.93), SP (0.95), and ACC (0.92) with low computational demands (0.055–0.064 GFLOPS). Conclusions: The model’s innovative Mamba-UCM layer significantly enhanced feature learning while maintaining efficiency that is suitable for mobile devices. MUCM-Net establishes a new standard in lightweight skin lesion segmentation, balancing exceptional ACC with efficient computational performance. Its ability to perform well on mobile devices makes it a scalable tool for early skin cancer detection in resource-limited settings. The open-source availability of MUCM-Net supports further research and collaboration, promoting advances in mobile health diagnostics and the fight against skin cancer. MUCM-Net source code will be posted on https://github.com/chunyuyuan/MUCM-Net. Original Article Fri, 25 Oct 2024 00:00:00 GMT ChunyuYuan, DongfangZhao, Sos S.Agaian, Fri, 25 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001250 https://www.explorationpub.com/Journals/em/Article/1001251 Background: Rheumatoid arthritis (RA) is an autoimmune joint disease with systemic manifestations. Emerging evidence implicates the gut microbiota in the pathophysiology of RA. However, the specific changes in the gut microbiota in RA patients remain poorly understood. Methods: We conducted a comprehensive search of PubMed, EMBASE, Web of Science, Cochrane Library, MEDLINE, Wanfang, VIP, CBM, and CNKI from the time the databases were created until October, 2023. To evaluate changes in α-diversity and the abundance of certain microbiota families in RA, standardized mean difference (SMD) and 95% confidence interval (CI) calculations were made. Results: Firstly, we evaluated the changes in α-diversity of gut microbes in patients with RA compared to healthy controls. Our analysis of 18 studies revealed a significant decrease in richness and evenness among RA patients. Importantly, the subgroup analysis suggested the decrease in α-diversity was more significant in treatment naïve patients rather than those who received anti-rheumatic medication. Additionally, in the subgroup analysis of 316 patients stratified by baseline disease activity, no significant differences in α-diversity were detected between groups. Discussion: Our analysis further evidence of altered α-diversity and the relative abundance of specific bacteria in RA. These findings contribute to our understanding of the role of gut microbiota dysbiosis in the pathogenesis of RA. Further research is warranted to elucidate the underlying mechanisms and explore the potential therapeutic implications of targeting the gut microbiota in RA management. Meta-Analysis Fri, 25 Oct 2024 00:00:00 GMT Qin-YiSu, YanZhang, DanQiao, XiaSong, YangShi, Rong-QiLi, Ying-FangZhang, Sheng-XiaoZhang, Fri, 25 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001251 https://www.explorationpub.com/Journals/em/Article/1001252 Aim: The cardio-ankle vascular index (CAVI) is a new evaluation indicator for arteriosclerosis. This study investigated the relationship between the CAVI and lipid levels in patients with hypertension in a real clinical environment. Methods: This descriptive study enrolled 2,656 patients (male/female: 1,016/1,640) from the Outpatient Department of Vascular Medicine of Peking University Shougang Hospital and Jinding Street Community Health Service Center. CAVI was measured using a VaseraVS-1000 vascular screening system (Fukuda Denshi, Tokyo, Japan). Results: Age, body mass index (BMI), waist circumference, hip circumference, CAVI, systolic blood pressure (SBP), diastolic blood pressure (DBP), creatinine, fasting plasma glucose (FPG), uric acid (UA), hypersensitive C-reactive protein (hs-CRP), homocysteine, HbA1c, and triglyceride (TG) were significantly higher in the hypertension group than in the non-hypertension group. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were significantly lower in the hypertension group than in the non-hypertension group. The CAVI value was significantly higher in patients with hypertriglyceridemia and normal LDL-C than in those with normal TG and hyper-LDL-C. Age, waist circumference, UA, FPG, HDL-C, hs-CRP, HbA1c, BMI, SBP, and DBP were independently associated with CAVI in all patients. Beta blockers were negatively correlated with CAVI (β = –0.411, P = 0.011). Sex (male) and history of hypertension and diabetes mellitus were positively correlated with CAVI (β = 0.419, P < 0.001; β = 0.247, P = 0.011; β = 0.638, P < 0.001; respectively). Conclusions: The CAVI was significantly higher in patients with hypertension and exhibited differences based on sex. Although we did not find a significant correlation between CAVI and TG, it remains crucial to maintain blood pressure to prevent the development of arteriosclerosis. Original Article Thu, 31 Oct 2024 00:00:00 GMT JinboLiu, HuanLiu, HongweiZhao, NaZhao, HongyuWang, Thu, 31 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001252 https://www.explorationpub.com/Journals/em/Article/1001253 Hyperuricemia (HUA), defined by elevated serum uric acid levels, is well-established in its association with systemic conditions like gout and cardiovascular diseases. Recently, however, emerging research has revealed a potential connection between HUA and ocular disorders, particularly epiretinal pathologies. This review investigates the pathophysiological mechanisms linking HUA to epiretinal conditions, including epiretinal membrane formation, macular edema, and retinal vascular diseases. By thoroughly analyzing current literature, this review seeks to deepen the understanding of the relationship between HUA and epiretinal disorders, with the aim of informing new therapeutic strategies and enhancing patient outcomes. Review Thu, 31 Oct 2024 00:00:00 GMT Chun-YaoCheng, Ju-ChiLiu, Huan-YuanChen, Jin-JerChen, Wen-RuiHao, Tzu-HurngCheng, Thu, 31 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001253 https://www.explorationpub.com/Journals/em/Article/1001262 Aim: Gingivitis is the most prevalent periodontal infection in children and adolescents. Various salivary markers have become potentially important in the early diagnosis of oral diseases, and some salivary amino acids play a significant role in predicting periodontal status. Therefore, this study investigated the relationship between the concentration of hydroxyproline in unstimulated saliva and the occurrence of gingivitis in 6–7 years children. Methods: This case-control study was conducted on children aged 6–7 years in elementary schools in Birjand from November 2022 to June 2023. A boy’s school was randomly selected based on the list of primary schools in Birjand city. Then, among the students in the first grade of elementary school and after the initial examinations, they were assigned to study groups according to the presence of inflammation in the gums and consent to participate in the study. Data analysis was done using SPSS-19 and statistical tests such as chi-square and Mann-Whitney U tests were employed for data analysis at a significance level of 5%. Results: The unhealthy group had poorer dental health compared to the healthy group (P = 0.013) and there were no differences in the dental care attendance status of participants between the two groups (P = 0.288). The mean of salivary hydroxyproline levels in the unhealthy group was 0.197 ± 0.289 mg/L and in the healthy group was 0.079 ± 0.006 mg/L. This difference was statistically significant between 2 study groups (P = 0.001). Conclusions: It can be concluded that the level of hydroxyproline in unstimulated saliva samples can be used as a biomarker in the diagnosis of gingivitis. However, to confirm the results of this study, further studies with a larger sample size comparing different severities of periodontitis such as mild, moderate, and severe forms are needed. Original Article Fri, 22 Nov 2024 00:00:00 GMT MarziehMohammadi Moghadam, HadiNasiroddini, FreshtehOsmani, Fri, 22 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001262 https://www.explorationpub.com/Journals/em/Article/1001264 Aim: Rheumatoid arthritis (RA) is an autoimmune disorder marked by an overgrowth of joint tissue and inflammation of the synovium. The mammalian target of rapamycin (mTOR), functioning as a serine/threonine protein kinase, is recognized for its role in controlling cell proliferation, metabolism, and inflammatory responses. While there is some evidence hinting at a link between RA and proteins downstream of mTOR, the findings are not definitive. In light of this, we have undertaken a Mendelian randomization (MR) analysis to investigate the potential connection between mTOR and RA. Methods: A two-sample MR study was performed by utilizing significant single nucleotide polymorphisms (SNPs) derived from a comprehensive genome-wide association study (GWAS) dataset, which included 58,284 samples of RA and 3,301 samples of mTOR-related proteins, as instrumental variables (IVs). The primary MR analysis techniques employed were inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression. Additionally, sensitivity analyses were carried out on the IVs to evaluate heterogeneity and pleiotropy using MR-Egger, leave-one-out, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Furthermore, to validate the robustness of the findings, replication analyses were also conducted using another RA GWAS dataset focusing on European populations. Results: The main findings indicated that there is no causal link between mTOR-related proteins and RA. The genetically elevated levels of mTOR-related proteins do not appear to raise the risk of RA [AKT (p = 0.721), ATF6 (p = 0.369), ATG7 (p = 0.112), BECN1 (p = 0.599), EIF4A3 (p = 0.652), EIF4B (p = 0.989)]. Additionally, the Cochran’s Q test did not detect any heterogeneity across all proteins. The MR-PRESSO analysis also found no evidence of pleiotropy. The replication cohort confirmed these results, showing once more that there is no connection between mTOR and RA, which suggests that the initial findings are both robust and reliable. Conclusions: Although earlier research has hinted at a possible link between mTOR pathway proteins and RA, our study does not endorse a causal relationship between the two. Additional studies are required to clarify the intricate mechanisms that drive RA and to determine the role of mTOR signaling in the disease process. Original Article Mon, 25 Nov 2024 00:00:00 GMT ZhoujunYuan, JiayiLi, RongZhao, HeyiZhang, ShengxiaoZhang, Mon, 25 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001264 https://www.explorationpub.com/Journals/em/Article/1001263 Immediate implant-supported rehabilitation of atrophic maxillae with a fixed screw-retained prosthesis has to deal with the fixtures’ disparallelism and a high risk of fracture of the fixture-abutment connecting screw. After the flapless placement of six implants, with the distal ones inclined at more than 30° to bypass the sinus cavities and reduce the cantilever effects, the provisional prosthesis was immediately connected. The low-profile OT Equator attachment system enabled a trustworthy anchorage of the superstructure without the connection-screws allocation on the rear fixtures. Three months later, all implants were definitively loaded. The patient was monitored for two years follow-up. No problem arose during the whole treatment. The prosthesis maintained its stability and anchorage with complete functional and aesthetic results. No signs of periimplantitis or radiographically evident bone loss were noted. The OT Bridge system successfully simplified the immediate loading of all implants regardless of the inclination of the rear fixtures, avoiding a provisional mobile denture. Case Report Fri, 22 Nov 2024 00:00:00 GMT GerardoPellegrino, ZoranZaccheroni, VittorioChecchi, GiuseppeLizio, Fri, 22 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001263 https://www.explorationpub.com/Journals/em/Article/1001265 Aim: Head and neck squamous cell carcinoma (HNSC) is a major contributor to the global cancer burden. The serine protease inhibitor Kazal-type (SPINK) gene family has been linked to various cancers. This study explores the prognostic value of SPINK genes in predicting overall survival (OS) in HNSC patients. Methods: We analyzed RNA sequencing and clinical data from 504 cancer and 44 non-cancer samples from the TCGA database. Differential expression and functional enrichment analyses gene ontology and Kyoto encyclopedia of genes and genomes (GO and KEGG) were performed using clusterProfiler. Protein-protein interaction (PPI) networks were built with STRING and visualized. Immune infiltration was evaluated using single-sample Gene Set Enrichment Analysis (ssGSEA). Survival analysis utilized Kaplan-Meier curves and Cox regression models. Results: Our results showed that SPINK5, SPINK7, SPINK8, SPINK9, and SPINK14 were significantly overexpressed in normal tissues compared to carcinoma tissues, whereas SPINK1, SPINK4, and SPINK6 showed higher expression in carcinoma tissues. Correlation analysis revealed significant relationships among SPINK family members. GO and KEGG analyses highlighted their involvement in processes such as negative regulation of peptidase activity and serine-type endopeptidase inhibitor activity. PPI network analysis indicated close interactions between several SPINK proteins and other relevant proteins. Immune infiltration analysis showed that NK cells and Th2 cells were negatively correlated with SPINK genes, while mast cells and neutrophils were positively correlated. Survival analysis revealed that high mRNA expression levels of SPINK1, SPINK5, and SPINK6 were significantly associated with OS in HNSC patients. Receiver operating characteristic (ROC) curve analysis indicated that these genes have diagnostic value. We developed a nomogram model that combines tumor stage and SPINK gene expression providing a predictive tool for patient prognosis. Conclusions: This study elucidates the multifaceted roles of the SPINK gene family in HNSC. These findings offer valuable insights into their potential as diagnostic biomarkers and therapeutic targets. Original Article Tue, 03 Dec 2024 00:00:00 GMT ChaoMa, HaoyuLi, Tue, 03 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001265 https://www.explorationpub.com/Journals/em/Article/1001266 Molluscum contagiosum (MC) is a common skin infection caused by a poxvirus, primarily affecting children and immunocompromised adults. It manifests as single or multiple raised, pearl-like papules and is highly contagious, spreading through skin contact or contaminated objects. Traditional treatments include cryosurgery, curettage, and pulsed dye laser ablation. However, in early 2024, berdazimer topical gel, 10.3% (ZELSUVMITM), was approved as the first topical treatment for MC. This review explores the potential of Zelsuvmi gel as a significant advancement in treatment due to its nitric oxide (NO)-producing properties. NO is a naturally occurring molecule in the body with multiple roles, including immune defense, antimicrobial activity, and modulation of apoptosis, inflammation, and cytokine production. The novel mechanism of action of Zelsuvmi, utilizing NO’s antiviral properties, has demonstrated compelling efficacy in clinical settings. The article also considers the broader implications of this treatment, not only for current dermatological practice but also for future research into innovative therapies for viral skin infections. Through an evaluation of clinical data, this review highlights Zelsuvmi’s potential to transform treatment approaches for MC, offering a non-invasive, effective option that may influence both clinical management and future prevention strategies. Mini Review Tue, 03 Dec 2024 00:00:00 GMT FatimaLaique, MuhammadHaris, MubashirMohiuddin, RijjaAhmed, Noor UlAin, Qurat UlAin, BibekGiri, Tue, 03 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001266 https://www.explorationpub.com/Journals/em/Article/1001267 Metastasis causes a majority of deaths in breast cancer patients. Metastasis is the spread of cancer to distant sites in the body away from the primary tumor, creating secondary tumors, or metastases. A tumor metastasizes when cancer cells strategically regulate genes that play a role in angiogenesis, epithelial-mesenchymal transition (EMT), migration, invasion, and regulation of the cell cycle to bypass apoptosis and increase proliferation and stemness. Several transcription factors have also been identified to play a role in metastatic breast cancer, as they enable invasion, intravasation, transport, extravasation, and colonization of metastasis through other processes such as angiogenesis and EMT, making them a prime target for cancer treatment. Understanding how transcription factors play a role in breast cancer metastasis will enable the development of targeted therapeutics for breast cancer. This paper reviews the roles of E2Fs, hypoxia-inducible factors (HIFs), EMT master regulators, sex determining region Y (SRY)-related high-mobility group (HMG) box (SOX), E26 transformation-specific (ETS), Yin Yang 1 (YY1), forkhead box M1 (FoxM1), BTB domain and CNC homology 1 (Bach1), sineoculis homeobox homolog (SIX), runt-related transcription factor 2 (RUNX2), myelocytomatosis (MYC), Kruppel-like factors (KLFs), and c-Jun in breast cancer metastasis. Review Tue, 10 Dec 2024 00:00:00 GMT SpoorthiMarada, ChikezieMadu, YiLu, Tue, 10 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001267 https://www.explorationpub.com/Journals/em/Article/1001269 Aim: This study aimed to explore the feasibility and preliminary efficacy of cinobufacini in patients with oral premalignant lesions (OPLs). Methods: Patients with histologically confirmed OPLs participated in an open-label uncontrolled pilot clinical study and received a 4-week or 12-week treatment, the efficacy and safety of cinobufacini for the treatment of OPLs were assessed. Results: During the treatment course ranging from 4 weeks to 12 weeks, no one withdrew because of adverse effects, no one had clinical or histologic progressive disease. Of the 8 participants who took cinobufacini for 12 weeks, one had a complete clinical response, and 4 had a complete histologic response. Of note, 9 participants had varying degrees of pain reduction. Conclusions: This small pilot study supports the feasibility of a larger clinical trial to evaluate the efficacy of cinobufacini in the treatment of OPLs [Chinese Clinical Trial Registry (chictr.org.cn) identifier: ChiCTR2300068529]. Original Article Fri, 10 Jan 2025 00:00:00 GMT YangLiu, PingHuang, JieMing, YuhongWang, YuanyuanWang, MinghuiWei, YuanCui, JiaoWei, XinwenWang, Fri, 10 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001269 https://www.explorationpub.com/Journals/em/Article/1001270 Oral cancer is rare in Western nations but widespread in high-risk regions around the globe. Risk factors, such as tobacco usage, alcohol intake, and betel nut chewing, enhance the chance of the illness, making it mostly avoidable. Due to its high mortality, early detection is crucial. Prevention and diagnosis begin with oral mucosa lesions that may be malignant and local diseases that cause persistent inflammation. Clinical therapies for oral cancer mostly include surgery, radiation, and chemotherapy. Unsatisfactory therapeutic impact and harmful side effects remain clinical treatment’s key issues. Future research should examine the cancer microenvironment and treatment. This review examined oral cancer risk factors, preventative strategies, and early diagnostic approaches. This review also discusses immunotherapy methods for countering this fatal disease. Immunotherapy targeting the cancer microenvironment may provide a novel oral cancer treatment. Review Fri, 10 Jan 2025 00:00:00 GMT Mohd JavedNaim, Fri, 10 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001270 https://www.explorationpub.com/Journals/em/Article/1001271 Ventilator-associated pneumonia (VAP) is a common and serious complication in critically ill patients, particularly those requiring prolonged mechanical ventilation. Extensively drug-resistant (XDR) Acinetobacter baumannii has emerged as a significant threat in VAP cases, complicating treatment due to its exceptionally high level of antibiotic resistance. We present a case of a 62-year-old male patient with severe acute ischemic stroke, who developed VAP during his stay in the intensive care unit (ICU). Cultures confirmed XDR Acinetobacter baumannii as the causative organism. The infection was further complicated by the development of a lung abscess, a rare but severe consequence of VAP. The patient was treated with a targeted antimicrobial regimen consisting of colistin, vancomycin, and tigecycline. Despite the pathogen’s resistance profile, the patient’s infection showed gradual improvement with sustained treatment. However, the recovery process was significantly prolonged due to the complexity of the infection, necessitating extended supportive care during hospitalization. This case highlights the challenges posed by XDR infections in critically ill patients and the importance of a tailored antimicrobial approach to effectively manage severe complications such as lung abscess. Case Report Fri, 10 Jan 2025 00:00:00 GMT AmitKumar, RajeshChetiwal, NehaRana, AmanDubey, ShwetaTanwar, Fri, 10 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001271 https://www.explorationpub.com/Journals/em/Article/1001273 Alcohol is a well-known toxic etiologic factor for liver injury. Metabolic substrates of alcohol (especially acetaldehyde) have a major responsibility and genetic susceptibility, alterations in microbiota and immune system are important co-factors for this injury. Major injury in liver is hepatocellular lipid accumulation. Therefore the relationship between non-alcoholic and alcoholic fatty liver diseases should have been defined clearly. Recently two major liver committees adopted new terminologies such as metabolic-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related liver disease (MetALD), and alcoholic liver disease (ALD) instead of non-alcoholic fatty liver disease (NAFLD). These terminologies were based on the effects of metabolic syndrome on liver. Alcohol consumption was defined differently according to these nomenclatures. MAFLD defined alcohol intake (regardless of amount) as “dual etiology fatty liver disease” and the Delphi consensus defined MASLD, MetALD, or ALD according to daily consumption of alcohol amount. Review Mon, 13 Jan 2025 00:00:00 GMT MubinOzercan, AhmedTawheed, MohamedEl-Kassas, Mon, 13 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001273 https://www.explorationpub.com/Journals/em/Article/1001274 Aim: The study aims to assess laypersons’ perceptions of smile aesthetics before and after gingival depigmentation and to correlate these perceptions with the degree of gingival pigmentation. Methods: The retrospective observational study examined individuals who received gingival depigmentation following orthodontic treatment between 2019 and 2024. Fifteen records were selected based on the inclusion and exclusion criteria. The pre- and post-depigmentation frontal smile photos were standardized, included into a Google Form, and distributed to 40 laypeople for the assessment of smile aesthetics. The laypeople evaluated the attractiveness of smiles using a 10-point Likert scale. Experienced periodontists classified the gingival pigmentation utilizing the oral pigmentation index (OPI). The differences between the pre- and post-treatment OPI scores and smile esthetic scores were assessed using Wilcoxon signed-rank test. Spearman correlation was used to evaluate the association between smile scores and OPI scores. The intraclass correlation coefficient (ICC) was employed to evaluate the inter-rater reliability of the smile ratings and OPI scores. The statistical significance was established at p ≤ 0.05. Results: The average OPI scores before depigmentation were 2.67 ± 0.49; however, following depigmentation, the scores significantly declined to an average of 0.33 ± 0.5 (p < 0.001). The mean smile aesthetic score pre-depigmentation was 6.72 ± 0.32, whereas after depigmentation the scores significantly improved to 7.91 ± 0.18 (p = 0.001). Spearman correlation indicated a statistically significant negative association between smile aesthetics scores and OPI scores (r = –0.76). ICC indicated excellent inter-rater reliability for the OPI (0.923) and good reliability for smile esthetic scores (0.756). Conclusions: The study found that gingival de-pigmentation procedures improve the OPI scores and laypeople perceive gingival hyperpigmentation unattractive. While gingival depigmentation is not mandatory, it may be recommended for individuals seeking cosmetic smile enhancements post-orthodontic therapy to improve the overall patient satisfaction. Original Article Wed, 15 Jan 2025 00:00:00 GMT PreethiRaj, ShwetaNagesh, RamanarayanaBoyapati, Wed, 15 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001274 https://www.explorationpub.com/Journals/em/Article/1001275 The gut microbiota, a complex ecosystem of microorganisms, plays an essential role in maintaining immune and metabolic homeostasis. Disruption of this microbial balance, known as dysbiosis, has been increasingly implicated in the pathogenesis of chronic inflammatory conditions, including cardiovascular, gastrointestinal, and autoimmune diseases, as well as metabolic disorders such as diabetes and obesity. A crucial mechanism through which the gut microbiota exerts its effects on host physiology is via the production of bioactive metabolites. These metabolites, including short-chain fatty acids, bile acids, and tryptophan derivatives, are key in modulating immune responses and regulating metabolic functions. Dysbiosis disrupts the production and function of these metabolites, thereby contributing to immune dysregulation, chronic inflammation, and disease progression. This review examines the role of gut microbiota-derived metabolites in chronic inflammatory diseases, with a focus on their immunomodulatory and metabolic effects. A deeper understanding of these mechanisms may open the way for novel therapeutic strategies aimed at restoring immune homeostasis and mitigating the global burden of chronic inflammatory diseases. Review Mon, 20 Jan 2025 00:00:00 GMT AlejandraVargas, Benjamin L.Robinson, KevinHouston, Ana RosaVilela Sangay, MichaelSaadeh, SteveD’Souza, David A.Johnson, Mon, 20 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001275 https://www.explorationpub.com/Journals/em/Article/1001278 Regenerating gene (Reg) was first isolated in 1988 and proposed to be specifically expressed in rat regenerating pancreatic islets. Since then, many genes homologous to Reg have been discovered in other species, including humans, mice, hamsters, rabbits, sheep, dogs, cats, pigs, giant pandas, chickens, and frogs. Moreover, Reg and its related genes (Reg family genes) have been classified as types I, II, III, and IV. They are closely associated with cell and tissue regeneration, cell proliferation, and anti-apoptosis in various tissues and cells including pancreatic β cells. In particular, focusing on the digestive organs and tissues, there have been reports that they play important roles not only in stomach, colon, liver, and pancreatic duct cancer, but also in intestinal epithelial cells, especially inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC). This review describes and discusses the expression of Reg family genes in intestinal epithelial cells of those affected by IBD and the molecular mechanisms underlying this expression. Review Thu, 06 Feb 2025 00:00:00 GMT ShinTakasawa, TomokoUchiyama, MaikoTakeda, Thu, 06 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001278 https://www.explorationpub.com/Journals/em/Article/1001276 Systemic hypertension, a significant global health issue and a leading risk factor for cardiovascular mortality affects half of the adult population, with increasing prevalence notably in low- and middle-income countries. Despite advancements in diagnosis and treatment, only one in four individuals with hypertension achieve satisfactory control over their condition. Medication adherence, critical for effective hypertension management, is complex and multifaceted. Non-adherence, encompassing late or non-initiation, sub-optimal implementation, and early discontinuation of treatment, is prevalent worldwide, with reported rates of anti-hypertensive medication non-adherence ranging from 30% to 40%. Adherence is influenced by various factors including drug regimen complexity, patient education, and socioeconomic status. Poor adherence is linked to increased cardiovascular risks and is compounded by clinical inertia among physicians. Addressing barriers to adherence and implementing evidence-based interventions can significantly reduce the global burden of hypertension and its associated complications. This review highlighted the critical need for improved adherence strategies to enhance hypertension management. It focused on novel tools such as mobile health interventions and regimen-simplification through single-pill combinations, which can improve treatment persistence and blood pressure control. Review Thu, 23 Jan 2025 00:00:00 GMT ClaudioTomasino, MarcoTomasino, Thu, 23 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001276 https://www.explorationpub.com/Journals/em/Article/1001277 The Age-Friendly Health System movement has been a unifying factor in caring for older adults at the University of Utah Health. Despite progress, challenges to efficient healthcare collaboration exist, particularly between geriatric primary care and oral health. This manuscript presents four of those challenges (lack of communication between medical and dental providers, the distance between medical and dental services, patient discomfort with the inclusion of oral health in primary health care, and provider discomfort in requesting oral health information in medical encounters) with the solutions derived at the University of Utah Health. Leaders at University of Utah Health developed five interventions to address these challenges (participation in the development of EPIC Wisdom©, a fully integrated oral health record in the electronic health record (EHR), co-location in new centers and oral health consultation in existing centers, implementing a geriatric health assessment that included oral health, widespread adoption of the 4 Ms framework). Applying the lessons learned from these challenges can benefit all older adults and may help prevent the conditions associated with periodontal disease. Perspective Thu, 23 Jan 2025 00:00:00 GMT Alberto EnriqueVarela, DonnaBaluchi, Timothy W.Farrell, José E.Rodríguez, Thu, 23 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001277 https://www.explorationpub.com/Journals/em/Article/1001279 Aim: Non-adherence is an important cause of uncontrolled hypertension. We investigated the prevalence of non-adherence to antihypertensive medications by serum drug concentration measurements in a cohort of Norwegian patients from the general population treated for hypertension. We also identified characteristics associated with non-adherence. Methods: Patients with hypertension using ≥ 2 antihypertensive agents were invited to participate in this national study performed in a semi-blinded fashion. Exclusion criteria were dementia, substance or alcohol abuse, pregnancy, terminal illnesses, poor Norwegian language skills, or severe kidney failure [glomerular filtration rate (GFR) < 30 mL/min/1.73 m2]. All patients had their antihypertensive drugs in serum analyzed by ultra-high-pressure liquid chromatography-tandem mass spectrometry to identify their adherence to the 23 most used antihypertensive agents. Additionally, they underwent a thorough standardized interview, office blood pressure (BP), and 24-hour ambulatory BP measurement. Results: n = 1,151 patients were investigated for BP control and drug adherence. Among these, n = 79 (6.9%) patients were identified as non-adherent, and n = 1,072 (93.1%) patients were identified as adherent by pharmacologists who reviewed the drug concentrations in blood in relation to self-reported prescribed medications. We found the non-adherent patients to be younger (56.9 vs. 63.7 years, p < 0.001), with higher systolic and diastolic office BP (150.4/91.4 vs. 143.2/82.0 mmHg, p < 0.01) and less likely to be of European ethnicity (82.9% vs. 95.8%, p < 0.001). Factors associated with non-adherence in logistic regression analysis were age, number of antihypertensive pills, non-European ethnicity, and inversely the use of angiotensin receptor blockers. Conclusions: We found fewer non-adherent patients than expected in patients on ≥ 2 antihypertensive drugs compared to previous investigations of patients on ≥ 3 antihypertensive drugs. We believe that selection at inclusion or possibly a higher confidence in physicians’ authority may be of importance. Adherence was significantly and negatively related to younger age, non-European ethnicity, and increasing number of prescribed antihypertensive pills, and positively to the type of prescribed medication, especially angiotensin receptor blocker (www.ClinicalTrials.gov identifier: NCT03209154). Original Article Sat, 08 Feb 2025 00:00:00 GMT EirikOlsen, Lene V.Halvorsen, StineRognstad, ArleenAune, Karl MariusBrobak, Ola UndrumBergland, Vibeke N.Kjær, KnutLiestøl, Marit D.Solbu, RuneMo, EvaGerdts, MortenRostrup, Sverre E.Kjeldsen, AudHøieggen, Mimi S.Opdal, Anne Cecilie K.Larstorp, Camilla L.Søraas, Sat, 08 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001279 https://www.explorationpub.com/Journals/em/Article/1001280 The International Agency for Research on Cancer (IARC) Monographs Programme plays an important role in cancer prevention by identifying potential carcinogenic hazards. However, the terminology used in IARC’s classifications and Monographs can confuse the public, health professionals, and policymakers. Terms like “carcinogenic to humans” imply causation, although classifications only indicate increased risk under certain conditions. For example, the lifetime incidence of mesothelioma among firefighters is approximately 14 in 10,000, compared to 7 in 10,000 in the general population. Despite doubling the risk, occupational exposure as a firefighter does not cause this type of cancer in 9,986 out of 10,000 firefighters. However, the IARC concludes that “occupational exposure as a firefighter causes mesothelioma” (IARC Working Group on the Identification of Carcinogenic Hazards to Humans. Occupational Exposure as a Firefighter. Lyon: IARC; 2023. pp. 1–730. PMID: 37963216). In addition, the lack of essential information about dosage and context in the IARC carcinogen lists can lead to agents with health benefits under certain conditions (e.g., solar radiation, red meat consumption, approved drugs) being perceived as universally harmful, discouraging beneficial exposures, behaviors, or treatments. Here, I propose renaming the groups of agents classified by the IARC and adding basic labels to specific agents to improve the accuracy and interpretability of the IARC classification lists. These adjustments do not interfere with the IARC’s objective of identifying potential hazards, are easy to implement, and enhance accuracy and clarity, providing stronger support to guide cancer prevention strategies. Perspective Sat, 08 Feb 2025 00:00:00 GMT MiguelLópez-Lázaro, Sat, 08 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001280 https://www.explorationpub.com/Journals/em/Article/1001281 Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging and rapidly growing health problem that currently affects more than one-third of the world general population and more than two-thirds of patients with obesity or type 2 diabetes. MASLD is associated with one or more cardio-metabolic risk factors (CMRFs) that determine the complexity of its natural history and management. Although the term MASLD encompasses a single disease, each CMRF has a different impact on MASLD, and the number of overlapping CMRFs results in a different rate of progression and outcomes of both liver and systemic disease. Its pathogenesis is characterized by insulin resistance, lipotoxicity and a complex cross-talk between liver, adipose tissue, muscle, intestine through the release of hepatokines, cytokines, myokines and inflammatory products. The stage of liver fibrosis is the best predictor of liver outcomes, such as liver failure and mortality, and also predicts the high risk of all-cause mortality associated with the disease. In many cases, the development of hepatocellular carcinoma (HCC) is associated with advanced fibrosis or cirrhosis, although it can occur at all stages of the disease, making prevention difficult. MASLD is characterized by increasing very low-density lipoprotein (VLDL) secretion and chronic low-grade systemic inflammation, which increase the risk of cardio-vascular, renal, and endocrine diseases and extrahepatic cancer. Thus, the management of MASLD requires a holistic approach and treatment of CMRFs through multispecialty collaboration. Currently, diet and physical activity are the effective first-line approaches. There are no approved drugs for the treatment of MASLD, apart from resmetirom, which in a percentage of cases improves metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. We summarize the wide and varied recent literature on the complex etiopathogenetic, clinical and therapeutic aspects of MASLD, connecting and interpreting it to facilitate clinical and management approaches. Review Tue, 18 Feb 2025 00:00:00 GMT Luigi ElioAdinolfi, AldoMarrone, LucaRinaldi, RiccardoNevola, AntonioIzzi, Ferdinando CarloSasso, Tue, 18 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001281 https://www.explorationpub.com/Journals/em/Article/1001282 Chronic pain, affecting approximately 30.3% of adults worldwide, presents a significant global health issue, severely impacting individuals’ quality of life and creating substantial socioeconomic challenges. Traditional pain management methods, such as physical therapy and pharmacological treatments, primarily focus on the biological aspects of pain while often neglecting the psychological and social factors. However, recent advancements in neuroscience have revealed that chronic pain is influenced by changes in the central nervous system, including mechanisms like central sensitization and neuroplasticity. This paper examines contemporary neuroscience-informed interventions, including Pain Neuroscience Education (PNE), mindfulness practices, and cognitive functional therapy (CFT), which target these neurobiological changes to improve pain perception and behaviors. These interventions help rewire the brain’s pain pathways, promoting long-term pain relief and functional recovery. Additionally, combining neuroscience-based approaches with conventional therapies has been shown to enhance treatment outcomes. This work emphasizes the need for personalized approaches and the integration of emerging technologies to enhance the accessibility and effectiveness of chronic pain management. Perspective Tue, 18 Feb 2025 00:00:00 GMT HyunjoongKim, Tue, 18 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001282 https://www.explorationpub.com/Journals/em/Article/1001283 Aim: The present study was designed to assess the effectiveness of topical application of sulfasalazine in combination with topically applied corticosteroids versus using topical steroids alone as the standard control in management of symptomatic oral lichen planus (OLP). Methods: The trial involved 46 participants having symptomatic OLP. Subjects included were divided into two equal groups at random. Group C (control group), in this group patients were treated with topically applied corticosteroids only as the standard treatment of OLP. In Group T (test group) topical sulfasalazine was used in combination with topical corticosteroids in management of the OLP cases. The patients used the topical applications four times per day in an alternate sequence (in Group T). The treatment schedule was continuous for 4 weeks with one visit weekly as a follow-up. Oral hygiene measures were strictly applied with total elimination of plaque with calculus deposits removal as they implement inflammation intra-orally and ‎exaggerate together distribution and signs of OLP lesions. Each group underwent pain assessment and sign score recordings both before and after the used management strategies. Results: The results of all patients reported no unwanted reactions or complications using both treatment strategies. Both study groups reported a significant decrease in the pain scale and sign score recordings over time as shown within the intragroup findings. Group T experienced a significantly higher reduction in pain scale (starting at two weeks) and sign score results (starting at three weeks) as compared to Group C. Conclusions: Based on the data presented in this study, combination of topical sulfasalazine with topical corticosteroids is an efficient treatment in management of OLP in terms of decreasing pain scale and sign score values (Clinical Trials.gov with registration number NCT06060301). Original Article Tue, 18 Feb 2025 00:00:00 GMT MaiZakaria, BasmaMostafa, IbrahimEl Refai, Tue, 18 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001283 https://www.explorationpub.com/Journals/em/Article/1001284 Aim: This study compared curved canal’s apical transportation by using Neoniti A1 with/without Neoniti C1 using cone-beam computed tomography (CBCT). Methods: This experimental in vitro study was conducted to analyze the mesiobuccal canals of extracted mandibular and maxillary molars (n = 62) with 20°–40° curvature. After determining the length of the roots, they were mounted in a custom-made holder and randomly sorted into two groups (n = 31). The roots underwent preoperative CBCT. Root canals in group 1 were only remodeled using the Neoniti A1 file while in group 2, the coronal third of the root canals was first prepared with Neoniti C1, and then the remaining part of the canal was instrumented with Neoniti A1. CBCT images were obtained again, and the preoperative and postoperative CBCT scans were compared using Romexis software to determine canal transportation at 3 mm, 5 mm, and 7 mm from the apex. Data analysis was done using SPSS 18. Results: Canal transportation was lower in the C1 + A1 group compared with the A1 group at all levels, but not significantly (P > 0.05). Canal transportation in both groups was < 0.03 mm at all levels from the apex. In the C1 + A1 group, canal centering was more elevated compared to the A1 group and at 3 mm from the apex, the two groups experienced a significant difference in centering ratio (P = 0.013). Conclusions: The use of Neoniti A1 files alone does not increase canal transportation in curved canals; however, the centering ability was higher in the use of C1 + A1. Therefore, coronal flaring is suggested. Original Article Tue, 18 Feb 2025 00:00:00 GMT SajjadAlipour, SediqeEbrahimipour, Tue, 18 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001284 https://www.explorationpub.com/Journals/em/Article/1001285 Team-based care is a patient management strategy involving a team of at least two healthcare professionals working collaboratively toward a shared clinical goal. This approach is now increasingly recommended by international hypertension guidelines mainly to improve medication adherence and hence, blood pressure control. The goal of this paper was to review the most recent evidence on the benefits of a team-based care approach in the management of hypertension. The results show that in recent years, numerous controlled clinical trials have demonstrated the efficacy of this strategy to lower blood pressure, achieve blood pressure targets more rapidly, and obtain more hypertensive patients under control. These improvements are due essentially to two factors: improved drug adherence/persistence and a reduction of therapeutic inertia. Best results are obtained when physicians collaborate with pharmacists and/or nurses, but other healthcare professionals may be involved successfully as well. Recent data have also demonstrated that the team-based care approach is cost-effective. These observations should be a strong incentive for hypertension centers to engage in the development of a team-based care strategy. Mini Review Tue, 18 Feb 2025 00:00:00 GMT MichelBurnier, Tue, 18 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001285 https://www.explorationpub.com/Journals/em/Article/1001286 Aim: Although xerostomia, smell, and taste dysfunctions are prominent signs of COVID-19 infection, long-term data regarding their prevalence and recovery rates is scarce. Accordingly, this study aimed to evaluate the frequency and persistence of xerostomia, taste, and smell disturbances in COVID-19 survivors over 3 years in an Egyptian sample. Methods: This cross-sectional study used an online questionnaire to assess the oral symptoms of xerostomia, which include altered taste and smell. Data was collected from 826 patients recovered from COVID-19. Results: Xerostomia was the most frequent finding affecting 73.6% of the studied sample, followed by smell disturbances affecting 67.8%, and altered taste reported by 54.6%. Xerostomia lasted less than 1 year in 48.3% of cases, up to 2 years in 10.4%, and up to 3 years in 7.2% of the study sample. Altered taste lasted less than 1 year in 77.8% of cases, up to 2 years in 2%, and up to 3 years in 0.4% of the study sample. Smell disturbances lasted around 1 month in 62.1% of cases, from 2–3 months in 36.1%, up to 1 year in 1.6%, and up to 2 years in 0.2% of the study sample. Xerostomia altered taste and smell, which impaired the quality of life and was more frequently observed in females than in males in the studied sample. Conclusions: COVID-19 has a major and long-term impact on oral health, with frequent, intense, and longstanding oral symptoms that may impair a patient’s quality of life. Original Article Wed, 19 Feb 2025 00:00:00 GMT DaliaGhalwash, AhmedHamdy, AsmaaAbou-Bakr, Wed, 19 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001286 https://www.explorationpub.com/Journals/em/Article/1001257 Background: Oral mesenchymal cells already have wide clinical applications based on their tissue regenerative abilities. The purpose of this study is to present the picture of scientific research on the application of mesenchymal cells. Methods: This review study presents data processing of selected articles on clinical application of oral mesenchymal cells as a future of technology with relatively reduced cost. As inclusion criteria, there are articles that evaluated the regenerative abilities of cells prior to their oral origin. The exclusion criteria are mainly laboratory procedural techniques of manipulation with mesenchymal cells. From 735 articles screened for retrieval, 148 articles were found. After application of exclusion criteria, it was reached in total, about 38 selected articles were analyzed based on combinations of keywords on the PubMed page. These articles were classified based on concrete positive results and evasive results of studies on the role, mechanism of action, and field of application of oral mesenchymal cells. Results: The selection ratio of mesenchymal cells of pulpal origin or of periodontium origin is based on the first type of cells. Regardless of the fact that the trend of their application is again in the oral cavity, in a smaller percentage they tend to be applied for tissue regeneration in other organs. Discussion: There is a lack of “in vivo” type studies. The trend of articles is about review-type studies on the field of application of oral mesenchymal cells. Articles, where the field of application of mesenchymal cells is beyond the oral cavity for the purpose of application in regenerative medicine, occupy a reduced percentage. There are significant differences between differentiating abilities depending on the source from which these cells are taken from the oral cavity. This ability can be modeled by using growth factors, cytokines, bioactive substances, or local anesthetics. Systematic Review Tue, 12 Nov 2024 00:00:00 GMT IlmaRobo, ManolaKelmendi, MalvinaDomgjoni, VeraOstreni, Tue, 12 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001257 https://www.explorationpub.com/Journals/em/Article/1001258 Aim: Periodontal diseases are prevalent and can be exacerbated by conditions such as obesity. Understanding the impact of obesity on periodontal health is crucial for developing effective management strategies. This study aimed to evaluate the effect of nonsurgical periodontal therapy on salivary visfatin levels and serum lipid levels in chronic periodontitis patients with or without obesity. Methods: A total of 40 patients aged between 20 to 50 years were enrolled in the study. Group 1 (obese group) included 20 chronic periodontitis patients with obesity while Group 2 (non-obese group) included 20 chronic periodontitis patients without obesity. Gingival index (GI), probing depth (PD), clinical attachment level (CAL), salivary visfatin, and serum lipid levels were measured before and six weeks after nonsurgical periodontal therapy (NSPT). Statistical tests were done to analyze the data in the study. Results: Mean GI scores, mean PD scores, and mean CAL scores were significantly reduced before and 6 weeks after NSPT in both groups (p < 0.05). The mean salivary visfatin levels also demonstrated a statistically significant reduction between the obese and non-obese groups (p < 0.05). Similarly, the mean serum lipid levels significantly differed before and 6 weeks after NSPT in the obese group (p < 0.05). Conclusions: The current study suggests a significant correlation between GI, PD, CAL, salivary visfatin, and serum lipid levels in the obese group following NSPT. Original Article Thu, 14 Nov 2024 00:00:00 GMT AiswaryaPolumatla, AnumalaDeepa, RavindranathDhulipalla, Kishore KumarKaturi, RamanarayanaBoyapati, TejaswinPolepalle, Thu, 14 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001258 https://www.explorationpub.com/Journals/em/Article/1001259 Combined treatment of photobiomodulation therapy and pilocarpine hydrochloride (Salagen) helped a patient suffering from severe oral mucositis and malnutrition resulting from radiochemotherapy for head and neck cancers. This treatment sped up the patient’s healing process and improved his quality of life by stimulating cells and increasing saliva secretion. The severity of oral mucositis was measured according to the World Health Organization (WHO) scale and the oral mucositis assessment scale. This case report highlighted a new combination treatment that may be the key to successfully managing severe oral mucositis during radiochemotherapy without the need to stop or modify cancer therapy. Case Report Fri, 15 Nov 2024 00:00:00 GMT AyaDawoud Agha, MahmmoudAbdul-Hak, AudayAlbasher, MoudarBakkour, Fri, 15 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001259 https://www.explorationpub.com/Journals/em/Article/1001261 Hypertension (HTN) is connected to many complications such as stroke, heart attack, heart failure, and kidney damage. Aging, lifestyle modifications, and obesity are risk factors associated with arterial HTN. On the other hand, chronic kidney disease (CKD) is a gradually progressive disease that is associated with cardiovascular disease (CVD), HTN, anemia, electrolyte imbalance, acid-base abnormalities, and bone disease. Blood pressure (BP) in hemodialysis patients shows a dynamic nature during dialysis procedures, including intradialytic hypotension and/or intradialytic HTN. Even though hypotensive events are common in hemodialysis sessions, intradialytic HTN, in which the BP increases during and/or immediately after hemodialysis, was associated with a higher mortality risk. The prevalence of intradialytic HTN has been described in 5–20% of hemodialysis treatments. The coexisting comorbidities in CKD patients need adequate pharmacological treatment. As a result, CKD patients are at a high risk for polypharmacy, which causes an elevated risk for adverse drug effects and influences non-adherence to medication. In addition, it is required individualization of medication doses adapted to the decreased renal function according to the progression of CKD. The improvement of health literacy through suitable interventions can facilitate the perception of illness, resulting in high therapy adherence in such a group of patients. This review considers the aspects of HTN management and adherence to the treatment in patients in permanent hemodialysis therapy, contributing to the determination of more effective strategies for improved treatment compliance, aiming at the prevention of CVD in this patient population. Mini Review Tue, 19 Nov 2024 00:00:00 GMT VaiaRaikou, SotirisGavriil, Tue, 19 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001261 https://www.explorationpub.com/Journals/em/Article/1001255 Sodium-glucose cotransporter 2 (SGLT2) inhibitors are integral to diabetes treatment, facilitating renal glucose excretion and offering benefits in cardiovascular risk reduction, kidney function preservation, and weight management. However, their integration into diabetes care presents challenges due to associated adverse effects. This review assesses the efficacy of SGLT2 inhibitors in diabetes management. A comprehensive literature search using PubMed and Google Scholar yielded pertinent studies. Clinical evidence demonstrates the effectiveness of SGLT2 inhibitors in glycemic control and in reducing cardiovascular risks in diabetes patients. Moreover, these agents exhibit positive effects on cardiovascular and renal functions. Despite their therapeutic promise, careful consideration is warranted when integrating SGLT2 inhibitors into diabetes care. Common adverse effects such as genitourinary infections, hypoglycemia, and sporadic diabetic ketoacidosis necessitate rigorous patient monitoring and education. Nonetheless, SGLT2 inhibitors offer a comprehensive approach to diabetes management, showing efficacy across multiple domains. In summary, SGLT2 inhibitors play a crucial role in diabetes care, offering benefits beyond glycemic control. However, their use requires careful patient selection, education, and monitoring to manage associated risks effectively. Awareness of potential adverse effects is essential for optimizing the therapeutic benefits of SGLT2 inhibitors in T2DM (type 2 diabetes mellitus) management. Review Thu, 07 Nov 2024 00:00:00 GMT FarazulHoda, HarshaNegi, DigvijayaSaini, MawrahArshad, SidraZayed, Mukesh KumarRaut, Mohammad AnwarHabib, MohdAkhtar, Abul KalamNajmi, Thu, 07 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001255 https://www.explorationpub.com/Journals/em/Article/1001256 Age-related changes in the brain cause cognitive decline and dementia. In recent year’s researchers’ extensively studied the relationship between age related changes in functional connectivity (FC) in dementia. Those studies explore the alterations in FC patterns observed in aging and neurodegenerative disorders using techniques such as resting-state functional magnetic resonance imaging (rs-fMRI), electroencephalography (EEG) coherence analysis, and graph theory approaches. The current review summarizes the findings, which highlight the impact of FC changes on cognitive decline and neurodegenerative disease progression using these techniques and emphasize the importance of understanding neural alterations for early detection and intervention. The findings underscore the complexity of cognitive aging and the need for further research to differentiate normal aging from pathological conditions. rs-fMRI is essential for studying brain changes associated with aging and pathology by capturing coherent fluctuations in brain activity during rest, providing insights into FC without task-related confounds. Key networks such as the default mode network and front parietal control network are crucial in revealing age-related connectivity changes. Despite challenges like neurovascular uncoupling and data complexity, ongoing advancements promise improved clinical applications of rs-fMRI in understanding cognitive decline across the lifespan. EEG and magnetoencephalography (MEG) are cost-effective techniques with high temporal resolution, allowing detailed study of brain rhythms and FC. Recent studies highlight EEG/MEG’s potential in early Alzheimer’s disease detection by identifying changes in brain connectivity patterns. Integration of machine learning techniques enhances diagnostic accuracy, although further validation and research are necessary. Graph theory offers a quantitative framework to analyze cognitive networks, identifying distinct topological differences between healthy aging and pathological conditions. Future research should expand exploration into diverse neurodegenerative disorders beyond mild cognitive impairment, integrating neuroimaging techniques to refine diagnostic precision and deepen insights into brain function and connectivity. Review Fri, 08 Nov 2024 00:00:00 GMT P.V.N.N.Ranasinghe, Mapa S. T.Mapa, Fri, 08 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001256 https://www.explorationpub.com/Journals/em/Article/1001268 Aim: Using a dataset available from the NCBI Gene Expression Omnibus Repository, this in silico study investigated the differential expression of GPX4, the gene coding for the detoxifying enzyme glutathione peroxidase paired samples of AH (atypical hyperplasia) and corresponding histologically normal (HN) tissue from 17 women with AH and in four samples of normal breast tissue used as controls. Methods: The study focused on the genes (HMGCR, FDPS, FDFT1, and GGPS1) involved in the production and breakdown of isopentenyl-diphosphate, a key component for GPX4 biosynthesis. It also explored the connection between the expression of GPX4 and the genes (CCND1, CDK4, CDK6, and CDKN1B) associated with the cyclin D1-CDK4/6 complex. Results: Compared to HN tissue, AHs exhibited higher levels of GPX4 and HMGCR, supporting the functional connection between GPX4 synthesis and isopentenyl-diphosphate production. Additionally, AHs showed elevated levels of CCND1 and CDKN1B and decreased levels of CDK6. Compared to normal breast tissue, HNs showed similar alterations, suggesting that ferroptosis escape and uncontrolled proliferation are early molecular events in the neoplastic transformation. Compared to HN tissue, AHs also expressed high levels of GGPS1, a downstream gene of HMGCR, which leads to the synthesis of geranylgeranyl-diphosphate, a molecule essential for the post-translational modification of the proteins involved in the regulation of the Hippo signaling pathway. Conclusions: Although very preliminary, present results seem to suggest that blocking the mevalonate pathway by statins might, on the one hand, prevent AHs from escaping ferroptosis through depleting isopentenyl-diphosphate and, on the other hand, inhibit cell proliferation by controlling the Hippo pathway. Original Article Mon, 16 Dec 2024 00:00:00 GMT DanilaCoradini, Mon, 16 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001268 https://www.explorationpub.com/Journals/em/Article/1001254 Aim: Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the most common subtype. Despite recent advancements in diagnostics and therapies, only a small percentage of patients benefit from immunotherapies. This underscores the urgent need to identify prognostic biomarkers for accurately assessing outcomes and providing treatment recommendations for NSCLC patients. Single-cell RNA sequencing (scRNA-seq) has revealed the heterogeneity of tumor-associated macrophages. Macrophages consist of M0, M1, and M2 subsets. M1 macrophages are often associated with improved clinical outcomes in various malignancies. However, there are no systematic studies on risk biomarkers for prognosticating NSCLC. Methods: CIBERSORT was used to calculate the macrophage subset infiltration percentage in bulk RNA-seq data from TCGA and GEO. The M1-related module was identified using the WGCNA algorithm. Potential M1 macrophage prognosis-associated genes were defined as the overlapping genes between marker genes in the M1 subpopulation from scRNA-seq data and prognosis-associated genes in M1 infiltrating cells. Results: Four risk genes (ADAM19, ICAM3, WIPF1, and LAP3) were identified through LASSO and multivariate Cox regression analysis. Forest plots demonstrated that the scoring model was an independent risk factor. A nomogram was provided to predict the prognosis of NSCLC patients. Finally, we validated the four risk genes at the protein expression levels and for copy number variations. Conclusions: In summary, our studies identified four risk genes related to M1 macrophages and presented a risk-scoring system to predict the outcomes of patients with NSCLC by integrating bulk and single-cell data. Original Article Thu, 07 Nov 2024 00:00:00 GMT ZheLiu, FangLiu, Olutomilayo OlayemiPetinrin, MuhammadToseef, NanjunChen, ZhongxuZhu, Ka-ChunWong, Thu, 07 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001254 https://www.explorationpub.com/Journals/em/Article/1001260 Background: Parkinson’s, a degenerative disease characterized by motor and non-motor symptoms, gradually leads to disability and affects ordinary gestures, including patients’ home oral hygiene. Given that poor oral conditions, with decayed teeth, halitosis, and periodontal inflammation, can represent a critical issue in patients with low compliance in oral hygiene, the aim of this review was to investigate overall oral health in patients with Parkinson’s disease (PD). Methods: A search on PubMed, Cochrane Library and Scopus databases was conducted to identify relevant publications: studies concerning patients with PD, their oral health conditions, and oral hygiene, also in terms of inflammation and plaque control, were included. Risk of bias analysis and qualitative analysis were performed. Results: Of 226 records found through the electronic search, a total of 16 studies were finally included in the systematic review. Outcomes without consistent differences between PD patients and healthy patients (control group) mainly regarded: the frequency of brushing (at least twice a day), the brushing methods (generally variable) and the frequency of dental visits (mostly regular for both groups). In patients with PD, use of interdental devices was lower, and presence of plaque was higher: due to self-reported difficulties, 15–29% of them need help for oral care, against the 1% in the healthy group. Furthermore, the longer duration and higher severity of PD seem to adversely affect overall oral health conditions. Discussion: Since poor oral conditions of patients with PD are associated with their disability in conducting proper home procedures, it is necessary for dental practitioners to focus on specific and personalized instructions, to be easily delivered to caregivers. Systematic Review Tue, 19 Nov 2024 00:00:00 GMT AlessiaPardo, AliceBarilli, AnnaritaSignoriello, MirianaGualtieri, GabrieleBrancato, GianlucaColapinto, GiorgioLombardo, MassimoAlbanese, Tue, 19 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001260 https://www.explorationpub.com/Journals/em/Article/1001272 According to research, hepatocellular carcinoma (HCC), ranks third globally in terms of cause of death and is the fifth most common type of cancer overall. Finding novel means of diagnosis and treatment is therefore crucial. The use of nanotechnology as a cancer treatment has drawn a lot of interest recently. Despite significant advancements in detection and treatment, there is still a long way to go before this disease is completely eradicated. Therefore, it’s critical to find innovative ways to diagnose and cure conditions. In particular, the substantial inertness of metallic nanoparticles (NPs) and their nanoscale structures, which have sizes comparable to many biological molecules, attract a great deal of interest in the biomedical field. Due to their exceptional optical qualities, chemically modified surface through the attachment of various ligands, biocompatibility (bio-inertness and low cytotoxicity), and superior optical properties, gold NPs (AuNPs) have garnered significant interest. The current review discusses the efficiency of AuNPs in various fields, including imaging, immunotherapy, and photothermal therapy for treating liver cancer. Finally, this review summarized the limitations of the prospects of the AuNPs. Review Mon, 13 Jan 2025 00:00:00 GMT SarmisthaSaha, ManasTaneja, SnehaDubey, AlokBhardwaj, Mon, 13 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001272 https://www.explorationpub.com/Journals/em/Article/1001287 Aim: To assess the predictive and prognostic role of HLA class I expression in patients with melanoma (Mel), and soft tissue sarcomas (STS) treated with autologous dendritic cell vaccine (DCV) (CaTeVac). Methods: From 2009 to 2023, 277 patients with Mel (143), and STS (134), received DCV at the N.N. Petrov National Medical Research Center of Oncology in adjuvant (78.3% and 14.9%) and therapeutic (21.7% and 85.1%) setting. HLA-typing was performed using a polymerase chain reaction with sequence-specific primers (PCR-SSP). Progression-free survival (PFS) and overall survival (OS) grouped by the presence of HLA alleles or HLA association rules were assessed using the Kaplan-Meier method (medians of survival in the month are presented). Results: Higher OS (41.1 vs. 22.1, P = 0.026) and PFS (6.0 vs. 3.9, P = 0.045) were found in HLA-A heterozygous STS patients, while HLA-B homozygous patients showed better OS (36.4 vs. 87.2, P = 0.023). HLA-A heterozygous Mel patients showed lower PFS (8.3 vs. not reached, P = 0.013). Association rules analysis on HLA expression revealed 20 rules with high confidence, seven of which were associated with the survival. HLA-B*07 and HLA-C*07 (21.2 vs. 52.2), HLA-B*40 and HLA-C*03 (17.6 vs. 45.4), HLA-A*02 and HLA-B*07 and HLA-C*07 (16.8 vs. 47.0), HLA-A*02 and HLA-С*07 (17.6 vs. 41.1), HLA-B*40 and HLA-A*02 and HLA-C*03 (8.3 vs. 50.2) decreased OS in STS (P < 0.05). HLA-A*02 and HLA-B*07 and HLA-C*07 (3.2 vs. 6.0), HLA-B*40 and HLA-A*02 and HLA-C*03 (3.2 vs. 5.9) decreased PFS in STS patients (P < 0.05). HLA-B*35 and HLA-C*04 increased median OS in STS from 33.4 to 153.3 months. Conclusions: HLA class I phenotype has a different impact on the survival in Mel and STS patients. The association rules based on HLA coexpression may have prognostic and predictive value. Further investigations of these parameters are warranted (The Trial Registration Number: NCT05539677). Original Article Fri, 28 Feb 2025 00:00:00 GMT Tatiana L.Nekhaeva, Aleksei V.Novik, Dmitry V.Girdyuk, Anna B.Danilova, Polina A.Savchenko, Alina V.Grigoryevskaya, Maria A.Nekrasova, Natalia A.Efremova, Andrey V.Orekhov, Irina A.Baldueva, Fri, 28 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001287 https://www.explorationpub.com/Journals/em/Article/1001288 Aim: Cough is an important symptom of the combined course of bronchial asthma (BA) and allergic rhinitis (AR) and/or allergic rhinosinusitis (ARS), but the contribution of the pathology of the upper and lower airway to the formation of cough in these patients cannot be considered established. The aim of the study was to evaluate the relationship of cough intensity with indicators of external respiration and nasal respiratory function in children and adolescents with a combined course of BA and AR and/or ARS. Methods: It was a single-center observational transverse pilot study. The absence and/or presence of cough and its intensity were scored in 122 patients (14.0 [11.0; 16.0] years) using the Sinonasal Outcome Test–22 (SNOT-22). Groups were identified: 1 (n = 29)—no cough (0 points), 2 (n = 72)—mild cough (1–2 points), 3 (n = 21)—moderate cough (3–4 points). Peak nasal inspiratory flow (PNIF) and spirometric parameters were measured. Results: Assessment of cough by patients using the SNOT-22 test had negative correlations with spirometric indicators: z FEV1 and z FEV1/FVC (r = –0.23, P = 0.012 and r = –0.21, P = 0.023, respectively). A positive relationship was noted with changes in FEV1 in tests with bronchodilators (r = 0.43, P = 0.002) and with the severity of postnasal drip (r = 0.45, P < 0.001 and r = 0.43, P < 0.001, respectively). Conclusions: Established correlations of cough intensity with spirometry indicators and with symptoms of postnasal drip in patients with combined BA and AR/ARS indicate the participation of both the upper and lower respiratory tract in the formation of cough. Original Article Fri, 28 Feb 2025 00:00:00 GMT Regina N.Khramova, Svetlana V.Krasilnikova, Anna S.Kolesnik, Ksenia V.Gorbunova, Dmitry Yu.Ovsyannikov, Alexey A.Khramov, Anastasiia A.Shamrikova, Georgii S.Ignatov, Maxim A.Karpenko, Nailya I.Kubysheva, Olga V.Khaletskaya, Viktor V.Novikov, Vilya A.Bulgakova, Natalia A.Geppe, Tatyana I.Eliseeva, Fri, 28 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001288 https://www.explorationpub.com/Journals/em/Article/1001289 This review explored the physiological mechanisms underlying arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus) and AVP resistance (AVP-R, formerly nephrogenic diabetes insipidus), with a focus on water balance regulation. Vital components include the hypothalamic-pituitary-AVP axis, renal AVP responsiveness, and neural mechanisms of thirst regulation. Recent insights on thirst generation within circumventricular brain nuclei (subfornical organ, median preoptic nucleus, and organum vasculosum of the lamina terminalis) are discussed, along with the diagnostic utility of copeptin in polyuric states. This review highlighted the critical role of hypothalamic-pituitary integrity and renal AVP responsiveness in maintaining water-electrolyte homeostasis. Understanding these mechanisms provided the foundation for optimizing therapeutic strategies and advancing research on AVP-related disorders. Review Fri, 28 Feb 2025 00:00:00 GMT Osah MartinsOnwuka, Fri, 28 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001289 https://www.explorationpub.com/Journals/em/Article/1001290 Aim: This randomized clinical trial aimed to investigate the chemo-preventive role of thymoquinone in Nigella sativa extract in managing oral leukoplakia clinically, histologically, and at the molecular level. Methods: A total of 48 patients with oral leukoplakia were randomly allocated to three groups; Group A received local muco-adhesive tablets with Nigella sativa extract in 10 mg/kg dose, for three months, Group B same intervention but with Nigella sativa extract in 5 mg/kg dose, and lastly Group C was the placebo group. The outcomes assessed were clinical improvement, histologic improvement (degree of dysplasia), and molecular biomarkers Ki-67 and caspase-3 by immunohistochemistry. Results: There was a statistically significant decrease in lesion size in Groups A and B compared to the placebo group. At the molecular level, there was a statistically significant decrease in the expression of Ki-67 in both the Nigella sativa groups compared to the placebo group. While there was a statistically significant increase in caspase-3 in Group A only compared to the other groups. Conclusions: Thymoquinone in Nigella sativa extract is a promising chemo-preventive agent that can be used in the management of oral leukoplakia (the trial is registered on clinicaltrials.gov identifier: NCT03208790). Original Article Tue, 04 Mar 2025 00:00:00 GMT GhadaNabil, Fat’heya M.Zahran, AliaaElMeshad, AhmedFawzy, DaliaGhalwash, BasmaElsaadany, Tue, 04 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001290 https://www.explorationpub.com/Journals/em/Article/1001291 Esketamine, the S-enantiomer of ketamine, has gained prominence as an adjunct in pain management during general anesthesia due to its higher potency and ability to achieve therapeutic effects at lower doses than ketamine. While its benefits for pain relief and mental health are well-established, the specific effects of esketamine on cardiac function during anesthesia remain under investigation. Anesthesia itself induces physiological changes in the cardiovascular system, and esketamine can exacerbate these effects by increasing sympathetic activity, heart rate, blood pressure, and cardiac output. Additionally, it can induce peripheral vasoconstriction, raising systemic vascular resistance. These cardiovascular effects are particularly concerning in patients with pre-existing heart conditions, underscoring the importance of preoperative assessment, continuous monitoring, and potential dose adjustments. This review examined the hemodynamic effects of esketamine, the associated cardiovascular risks, and the clinical implications for patients with cardiac conditions, offering recommendations for its safe use in anesthesia. Mini Review Tue, 04 Mar 2025 00:00:00 GMT EdwardSun, YuxianLiu, JingpingWang, Tue, 04 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001291 https://www.explorationpub.com/Journals/em/Article/1001292 Cervical cancer is the fourth leading cause of cancer-related deaths among women worldwide, causing over 660,000 new cases and 350,000 deaths in 2022, with a disproportionately high burden in low-resource countries where access to treatment is limited. Human papillomavirus (HPV) is a common sexually transmitted infection that accounts for approximately 95% of cervical cancer cases. Persistent HPV infection can progress to cervical dysplasia, categorized into varying severities (CIN1, CIN2, and CIN3), which significantly increases cancer risk. The mechanism of HPV-induced malignancy involves the disruption of cellular apoptosis by integrating viral genetic material into cervical cells, particularly within the transformation zone. The viral proteins E6 and E7 play pivotal roles in cervical carcinogenesis by inhibiting tumor suppressor proteins, promoting uncontrolled cell proliferation, and evading immune responses, ultimately driving progression toward malignancy. Timely detection and intervention are essential for managing HPV-related cervical cancers. Preventative measures such as HPV vaccination have demonstrated substantial efficacy. Six vaccines targeting high-risk (HR) HPV strains are recommended before sexual activity or exposure. Despite these advancements, barriers, such as misinformation, logistical challenges, and limited healthcare infrastructure, persist, particularly in underserved regions. Advances in diagnostic and therapeutic technologies have offered new avenues for addressing these challenges. Next-generation sequencing and CRISPR gene editing are emerging as promising tools for HPV-related cancer treatment that enable precise and targeted interventions. Furthermore, artificial intelligence (AI) and imaging innovations have significantly enhanced diagnostic accuracy and personalized care. Pap smears and HPV DNA testing are indispensable tools for early detection. To tackle HPV-related cervical cancer globally, a multifaceted approach is required. Public health education, vaccination programs, research, and international collaboration are crucial. Public health campaigns should combat misinformation, strengthen vaccination programs, and focus on novel therapies, screening technologies, and next-generation sequencing. Review Tue, 04 Mar 2025 00:00:00 GMT Racheal AhuoyizaAyeni, Blessing OlawunmiAmisu, Ayanleke RaphaelAyantunji, Mohamed MustafAhmed, Olalekan JohnOkesanya, TolgaKab, Bonaventure MichaelUkoaka, Tue, 04 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001292 https://www.explorationpub.com/Journals/em/Article/1001293 Aim: Angiogenesis is a universal hallmark of all cancers involving a variety of proteins including vascular endothelial growth factor (VEGF). Extensive studies have explored the potential implications of single nucleotide polymorphisms (SNPs) within VEGF-A in lung cancer (LC) susceptibility, tumor growth, and their effect on the gene expression level. Accordingly, we have planned in the present study to evaluate the prevalence of the -460T/C (rs833061), the -2578C/A (rs699947), and the -2549I/D (rs35569394) SNPs and their association with clinicopathological parameters and to assess their impact on the expression of VEGF-A, VEGFR-1, and VEGFR-2 to be used in the accurate management of LC in Morocco. Methods: A total of 60 fresh biopsies were collected from patients with primary LC and were subjected to polymerase chain reaction (PCR)-DNA sequencing of VEGF-A to detect -460T/C (rs833061), -2578C/A (rs699947), and -2549I/D (rs35569394) SNPs. Reverse transcription (RT)-PCR was used to evaluate VEGF-A, VEGFR-1, and VEGFR-2 expression levels. Results: Sequencing analysis revealed the occurrence of -460T/C, -2578C/A, and -2549I/D polymorphisms with different frequencies. VEGF-2549I/D polymorphism was associated with cancer staging for both genotypes and alleles distributions (p < 0.05). Overall, gene expression analysis revealed an overexpression of VEGF-A, VEGFR-1, and VEGFR-2. The expression of VEGFR-1 and VEGFR-2 was significantly associated with histological types (p = 0.0114). Of note, no significant correlation was obtained between VEGF-A expression and VEGF-A gene polymorphisms (p > 0.05). Conclusions: This study is very informative providing the first insight into polymorphisms and expression of VEGF ligand and its receptors in LC patients from Morocco. Globally, -2549I/D SNP and VEGFR-1 and VEGFR-2 expressions appear to be promising prognostic biomarkers and are likely potential keys for better management of LC. Original Article Tue, 11 Mar 2025 00:00:00 GMT YounesEl Founini, SaraHafidi, HindDehbi, MohammedAttaleb, MehdiKarkouri, SouheilBoubia, MohammedRidai, FadilaGuessous, MohammedEl Mzibri, ImaneChaoui, Tue, 11 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001293 https://www.explorationpub.com/Journals/em/Article/1001294 The advent of immunotherapy has revolutionized the therapeutic landscape of breast cancer. The immune checkpoint inhibitor drug, pembrolizumab, a monoclonal antibody targeting programmed cell death protein 1 (PD-1), was recently approved by the Food and Drug Administration (FDA) as a neoadjuvant treatment in combination with traditional chemotherapy in locally advanced triple-negative breast cancer (LA-TNBC). This manuscript aims to highlight an uncommon adverse event of immune checkpoint inhibitors (ICIs): hypereosinophilia (HE). Herein, we report the case of AW, a 49-year-old female patient, who was treated for triple-negative breast cancer (TNBC) with pembrolizumab, achieving a complete response. After undergoing surgery, pembrolizumab was reintroduced as adjuvant therapy, at which point an abnormal increase in eosinophil count was observed. Hence, treatment was interrupted, and after glucocorticoid administration, the eosinophil count reverted to normality. Our findings underscore the necessity for vigilant monitoring of blood eosinophil levels during pembrolizumab therapy and provide insights into the management of such immunotherapy-related adverse events. Case Report Fri, 14 Mar 2025 00:00:00 GMT RemoPoto, Antoniodi Salvatore, LauraStigliano, ElisabettaSimeone, Maria TeresaNarducci, MichelaWilliams, AlessandraCuomo, Carlo GabrieleTocchetti, Amatode Paulis, GildaVarricchi, Fri, 14 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001294 https://www.explorationpub.com/Journals/em/Article/1001295 Aim: A growing body of research suggests that acute myocardial infarction (AMI) may be an independent risk factor for cognitive impairment in patients with cardiovascular disease. The role of premature ventricular contractions (PVCs) or premature atrial contractions (PACs) occurring during the day has not been fully explored in this patient population. The objective of the study was to investigate the clinical and functional relationships between cognitive functions and the severity of daytime premature cardiac contractions, as well as echocardiographic parameters in patients with either old myocardial infarction (OMI) or recent AMI. Methods: The main group consisted of 32 patients who had experienced an AMI no more than seven days prior. The comparison group included 20 patients who had had one myocardial infarction more than one year earlier. All participants underwent a 24-hour Holter monitoring, Doppler echocardiography. Cognitive testing included the Mini-Mental State Examination, Wechsler Subtests 5 and 7, and the Bourdon Test. Statistical methods included multivariate analysis, univariate analysis of variance, canonical correlation analysis, nonparametric correlation analysis, and multivariate analysis was also performed using the generalized normalized log model. Results: In the patients of the main group, the characteristics of mental functions were worse than in the control group. The cognitive test scores were significantly correlated with the presence of akinesia zones in the myocardium, as well as with a higher grade of PVCs and a large number of PVCs during the day in patients with AMI. No significant correlations were found between cognitive test results and echocardiographic findings in the comparison group, a weak correlation was only noted between the number of PACs and cognitive test results. Conclusions: The presence of even non-life-threatening PVCs occurring within 24 hours may be a marker of significant cognitive deficit in the acute period of myocardial infarction. Original Article Fri, 14 Mar 2025 00:00:00 GMT NatalyaAkimova, Ekaterina E.Kutorova, Larisa E.Konshina, Alexander A.Ryabov, Yury G.Shvarts, Fri, 14 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001295 https://www.explorationpub.com/Journals/em/Article/1001296 Aim: Artificial intelligence (AI) has significantly influenced healthcare, enhancing diagnostic and therapeutic capabilities. This study evaluates the effectiveness of an AI-generated output within actual clinical environments, analyzing its precision compared to conventional interpretation techniques. Methods: A cross-sectional observational study assessed the reliability of the VELMENI AI platform in detecting dental issues on panoramic radiographs. Three hundred radiographs from the Sibar Institute of Dental Sciences were used, with four experienced readers trained on the AI platform. Each reader independently identified caries, restorations, and prostheses using the AI system. Diagnoses by dentists and the AI tool were compared, ensuring rigorous analysis and ethical standards. Results: This study examined the agreement between four human observers and an AI system in assessing caries, fixed prostheses, and restorations using Cohen’s weighted kappa. High reliability was found among the human observers, with the AI system demonstrating even greater consistency. The results were statistically significant, demonstrating strong agreement. Fleiss’ multi-rater kappa confirmed high overall agreement among all five raters. However, moderate agreement in caries assessment highlighted the need for enhanced training and guidelines. Conclusions: This study underscores AI’s potential in dental diagnostics, excelling in fixed prosthesis assessment while facing challenges in caries detection. Improved training and datasets are required for better clinician capabilities. The findings suggest AI-human collaboration is a promising future direction for dental diagnostics. Original Article Fri, 21 Mar 2025 00:00:00 GMT SamataYalamanchili, TejaswiChennupati, Purnachandra Rao NaikNunsavathu, SethumanjushaSaranu, PavaniKotha, SanjanaMarpuri, PranotiHiralkar, Fri, 21 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001296 https://www.explorationpub.com/Journals/em/Article/1001297 Aim: This study aimed to evaluate the efficacy of carboxymethyl cellulose (CMC)-based natural mixture of aloe vera gel and coconut oil as a salivary substitute in comparison to the conventional CMC for the management of xerostomia in a sample of patients with Sjogren’s syndrome (SS). Methods: This crossover randomized clinical trial included 24 patients diagnosed with SS. Half the patients started with the study treatment (A-Gel) for 2 weeks, then went through a 7-day washout period, then received the control treatment (B-Gel), while the other half had the order reversed. The measured outcomes were subjective oral dryness (Bother 1’ xerostomia index), modified xerostomia quality of life scale (XeQoLS), clinical oral dryness (CODs), and salivary candidal load. Results: With a mean age of 46.96 ± 11.86 years, all patients were female and suffered from mouth dryness for 16.58 ± 25.32 months. In light of our findings, both groups’ Bother 1’ xerostomia index values recorded at different intervals showed significant improvements. There was a p < 0.001 difference between the mean value for groups A and B at baseline (7.33 ± 2.39 and 7.29 ± 2.66), one week later (4.17 ± 2.24 and 4.25 ± 2.57), and two weeks later (2.83 ± 2.08 and 2.88 ± 2.07). However, there was no significant difference between the groups. Likewise, for CODs and modified XeQoLS, no significant difference was found between groups; however, both groups showed a statistically significant improvement (p < 0.001). Improvement in the modified XeQoLS was observed in all domains (physical functioning, pain & clinical acceptance). Regarding candidal load, there was no statistically significant difference between groups or even within groups (p > 0.05). Conclusions: As salivary substitutes, the CMC natural mixture (aloe vera, coconut oil) and the conventional CMC-based oral gel are equally efficient at minimizing xerostomia symptoms and enhancing SS patients’ quality of life with minimal side effects. Saliva’s natural effect might be substituted with a natural mixture of coconut oil, aloe vera gel, and CMC. The trial is registered on clinicaltrials.gov, identifier: NCT04252209. Original Article Fri, 28 Mar 2025 00:00:00 GMT AlaaMahmoud, BasmaElsaadany, MervatEissa, WesamAbd Elmoneim, SherifaTarek, MaiZakaria, Fri, 28 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001297 https://www.explorationpub.com/Journals/em/Article/1001298 The global epidemic of hypertension remains largely uncontrolled and is a leading contributor to noncommunicable disease deaths worldwide. Failure to detect and to adequately treat hypertension is the largest contributor to uncontrolled hypertension. Yet, suboptimal adherence, which includes failure to initiate a prescription for antihypertensive pharmacotherapy, to take medications as often as prescribed, and to persist on pharmacotherapy long-term, is a well-recognized factor contributing to uncontrolled hypertension. A large body of research has identified several variables including patient, sociodemographic, comorbid medical and behavioral conditions, therapy-related, healthcare team, and are associated with nonadherence. Unfortunately, these factors individually and even in combination are typically only weakly related to adherence of individual patients. A two-fold strategy can be efficiently applied in the clinical setting to improve adherence. First, address major categories of adherence throughout the therapeutic journey for all patients from initiation of pharmacotherapy to titration, and maintenance. Efficient, scalable strategies in this category include teach back, clarity on treatment goals including the blood pressure range required to attain consistent control, initiation, and titration of single-pill antihypertensive combinations, limiting out-of-pocket expense, and refill consolidation. Second, objectively assess adherence when treatment goals are not attained with effective pharmacotherapy. Then, identify and address patient-specific barriers for individuals with suboptimal adherence. Given the multiple competing priorities and resultant time demands on clinicians and healthcare teams, effective, replicable, and scalable strategies to optimize adherence are important in attaining the evidence-based benefits of antihypertensive pharmacotherapy. Review Fri, 28 Mar 2025 00:00:00 GMT Brent M.Egan, Fri, 28 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001298 https://www.explorationpub.com/Journals/em/Article/1001299 Aim: Amnestic mild cognitive impairment (aMCI) is a transitional stage toward Alzheimer’s disease (AD). For late-onset AD (95% of cases), aging is the main risk factor. Systematizing the transcriptome of hippocampal neurons under the native conditions of this disease is essential, as this information is scarce and the hippocampus is a highly vulnerable cerebral region. Methods: Public microarray data corresponding to homogenates of human hippocampus of Healthy-Younger, Healthy-Elder, and Elder-with-MCI individuals were re-analyzed herein. Through an optimized computational pipeline, those genes having splice forms and that belong to the neuronal type were identified. The differential genes arising from each group were then characterized by contrasting ontologies (functions, cellular components, and pathways). Additionally, the data were re-arranged factorially to determine the first- and second-order sex interactions. Results: Around 76% of the relevant changes actually occurred during the healthy-aging process, being further balanced or not during MCI. “Cognition”, “behavior”, “glutamatergic synaptic transmission”, “lipid rafts”, and “catecholamines” decreased across the three groups analyzed, whereas “associative/visual learning”, “gliogenesis”, “neuro-inflammation”, “corticosteroids”, “p75NTR”, “ER-stress” and “autophagy” peaked in Elders. On the contrary, “Learning/memory”, “GAP junctions”, “GABAergic transmission”, and “GNDF” showed a minimum in Elders. The “transcriptional regulators” (MeCP2, NPAS4, DREAM), “BNDF/NGFR”, “Ca2+ transport”, “CRHR1” and “CXCL12” were minimal in MCI. From Elder to MCI, “MAPKs”, “MEF2C”, “RGS7”, “CCKBR1”, “ErbB4”, “ERK5”, and “Ca2+-Na+-K+ channels” (RYR2, SCNA1/A8, KCNQ2/Q3, KCNN3, KCNIP2) appeared downregulated. “Long-term synaptic depression” (LTD) increased sharply in the MCI. Most of the findings detected were contrasted against 250 reports. Conclusions: The multiple alterations in the basic mechanisms—mainly in the CA3 dendrites of mossy fibers could be compatible with neuronal hyper-excitability, diminished synaptic transmission, and changes in the theta/gamma/SWR rhythms. Many functionalities appeared conditioned by sex-interactions. Particularly, women showed “pure” sex-effects and interactions with “cross-over” effects. Due to its consequences on the higher-order functions, all these predictions should be confirmed experimentally. Original Article Tue, 01 Apr 2025 00:00:00 GMT Daniel V.Guebel, Tue, 01 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001299 https://www.explorationpub.com/Journals/em/Article/1001300 Aim: Gasserian ganglion (GG) percutaneous neurostimulation is a key resource in treating chronic refractory facial pain. However, this procedure has complications, and the literature does not yet document a gold standard for tunneling techniques. The main objective of this study was to compare two different tunneling techniques for GG stimulation and report whether there were associations between the type and rate of complications. Methods: This was a retrospective analysis of medical records of all patients with refractory facial pain, who underwent GG stimulation between January 2010 and June 2022. From 2010 to 2015, the percutaneous GG stimulation procedure was performed with a tunneling technique which involved passing through the preauricular region. Since 2016, this procedure has been performed with a tunneling technique that involved passing directly into the patient’s neck. Results: GG stimulation for refractory facial pain was performed in 49 patients. One of them was implanted twice because of bilateral trigeminal neuropathy. The ear tunneling technique was used for 20 GG stimulation procedures while the tunneling technique involving direct passage of the lead into the neck was used for 30 procedures. The comparison of these two different tunneling techniques showed no statistically significant difference in terms of complications incurred (Fisher exact test, p = 0.451). In the group of patients with ear tunneling, erosion and fibrosis of the neck skin occurred in 20% of cases. This type of complication is not present in patients in whom the other tunneling technique was used. Conclusions: Both tunneling techniques were found to be safe, but the direct technique does not cause fibrosis and erosion of the neck tissues as a complication. Original Article Wed, 02 Apr 2025 00:00:00 GMT EdoardoPiacentino, AliJerjir, IrisSmet, MariekeDevos, PaolaPozzolo, Jean-PierreVan Buyten, Wed, 02 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001300 https://www.explorationpub.com/Journals/em/Article/1001301 Aim: Loperamide hydrochloride (HCl), a peripheral opioid receptor agonist primarily used as an antidiarrheal drug, has been reported to induce apoptosis in various cancer cell lines. However, its effects on oral cancer cells are yet to be ascertained. This study investigates the cytotoxic effects of loperamide HCl on oral squamous cell carcinoma (OSCC) cells, exploring its potential as a repurposed therapeutic agent. Methods: The OECM-1 OSCC cells were treated with various concentrations of loperamide HCl. The metabolic alterations of OECM-1 cells were spectrophotometrically assessed at 4, 24, 48, and 72 hours using the alamarBlue cell proliferation assay. The half-inhibitory concentration (IC50) of loperamide HCl on OECM-1 cells was calculated through non-linear regression analysis. Apoptosis was evaluated using the Caspase-3/7 assay. Results: Loperamide HCl suppressed OECM-1 cell proliferation after 24 hours. The IC50 values of loperamide HCl on OECM-1 cells were non-evaluable at 4 hours but progressively decreased to 80.82 µM at 24 hours, 37.69 µM at 48 hours, and 34.29 µM at 72 hours. Significant apoptosis was observed at loperamide HCl concentrations of 40 µM and 50 µM after 72 hours of treatment. Conclusions: Loperamide HCl demonstrates a time- and dose-dependent cytotoxic effect on OECM-1 cells, significantly inhibiting proliferation and inducing apoptosis at higher concentrations. The decreasing IC50 values over time indicate enhanced cytotoxicity with prolonged exposure. These findings suggest loperamide HCl’s potential as a therapeutic agent for OSCC. Original Article Wed, 02 Apr 2025 00:00:00 GMT Chie ChingTan, Ursula Siau LanTing, Zi XianKhoo, PrashantiChippagiri, Suan PhaikKhoo, Spoorthi RaviBanavar, Wed, 02 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001301 https://www.explorationpub.com/Journals/em/Article/1001302 Vanishing bile duct syndrome (VBDS) is a rare condition, representing approximately 0.5% of small bile duct diseases, characterized by progressive destruction of intrahepatic bile ducts, leading to ductopenia. This condition encompasses various etiologies, with drug-induced VBDS (D-VBDS) accounting for 7% of VBDS cases. D-VBDS arises from liver injury due to chemical drugs, traditional medicines, and dietary supplements, often resulting in inflammatory responses and necrosis of bile duct epithelium. Recent years have seen a rise in reported cases, making drug-related injuries a leading cause of acute liver failure in Western countries. This review provides a comprehensive analysis of VBDS, focusing on the histopathological features of acute and chronic D-VBDS, alongside exploring its clinical presentation, prognostic implications, and future research directions. Understanding the diverse etiologies, clinical manifestations, and biochemical parameters associated with D-VBDS is essential for improving diagnosis, treatment strategies, and patient outcomes. Review Wed, 09 Apr 2025 00:00:00 GMT SugunahSallapan, KyrillosFaragalla, Hanlin L.Wang, CherryPun, JiminLiu, Wed, 09 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001302 https://www.explorationpub.com/Journals/em/Article/1001303 Aim: To investigate the impact of socio-demographic characteristics on health-related quality of life (HRQoL) among dialysis (hemodialysis)-dependent chronic kidney disease (DD-CKD) patients. The findings aim to inform strategies for enhancing the overall well-being of CKD patients. Methods: This cross-sectional study was conducted at the nephrology clinic of GMCH, a public tertiary care hospital in Chandigarh, India, with a random sample of 104 participants. Data were collected using the Kidney Disease Quality of Life-Short Form (KDQOL-SF™) questionnaire and analyzed using SPSS (version 20.0). Baseline characteristics were described with descriptive statistics, and Cronbach’s α measured questionnaire reliability. Independent t-tests and ANOVA were applied to compare HRQoL scores across groups, while simple linear regression, logistic and multiple regression analyses examined associations between the variables. Results: This study assessed HRQoL in 104 DD-CKD patients (mean age 53.27 ± 13.67 years, HRQoL score 32.70 ± 6.00). Reliability was highest in the effect of kidney disease (EKD) domain (Cronbach’s α = 0.832). Higher incomes were linked to better physical component summary (PCS) (61.33 ± 12.92, p = 0.049), while unmarried patients had higher burden of kidney disease (BKD) scores (28.12 ± 16.47, p = 0.047). Hypertension (74.6%, p = 0.037) and alcohol use (75.0%, p = 0.013) were more common in males > 50 years, while > 50 years females had higher diabetes prevalence (50.0%, p < 0.001). These findings highlight the need for tailored, patient-focused care strategies. Conclusions: The study concludes that socio-demographics play a crucial role in influencing HRQoL in DD-CKD patients. Higher income levels and marital status were significantly associated with improved HRQoL scores, while age and gender impacted the prevalence of comorbidities and risk behaviors. These findings highlight the need for personalized, patient-centered care strategies to address physical, mental, and social challenges, ultimately improving the HRQoL for this functionally impaired population. Original Article Mon, 14 Apr 2025 00:00:00 GMT GautamSahu, PoojaArora, PramilTiwari, SanjayD’Cruz, AnitaTahlan, Mon, 14 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001303 https://www.explorationpub.com/Journals/em/Article/1001305 Aim: It has been shown that the vitamin D receptor (VDR) gene and its biological functions can be affected by genetic alterations in the VDR gene. These genetic alterations particularly (rs1544410), (rs7975232), and (rs731236) polymorphisms, and deficiency of vitamin D are suggested to contribute to predisposition to prostate cancer (PCa). Our case-control study investigates the association between VDR gene polymorphisms and PCa risk, in relation to clinicopathological features, within the Moroccan population. Assess the relationship between VDR polymorphisms (rs1544410), (rs7975232), and (rs731236) and PCa risk in Moroccan men and their association with clinicopathological characteristics. Methods: A total of 100 men patients (mean age of 69.8 years) with different stages of PCa were genotyped for three VDR gene polymorphisms, (rs1544410), (rs7975232), and (rs731236), as well as 100 healthy controls using the PCR-RFLP using restriction enzymes (BsmI, ApaI, and TaqI). The evaluation of the association between VDR genetic polymorphisms and clinicopathological features was carried out by the chi-square test (χ2) and the odds ratios (OR) with 95% confidence intervals (CI). Results: Significant associations were found between the ApaI (p = 0.045) and TaqI (p = 0.029) polymorphisms and the risk of PCa. The haplotypes AA (42%) of ApaI and Tt (45%) of TaqI were more frequent in PCa patients, suggesting an increased risk. The BsmI polymorphism was significantly associated with PSA levels (p = 0.045). Additionally, the ApaI polymorphism was linked to smoking status in PCa patients (p = 0.023), and TaqI was associated with pathological T stage (p = 0.042) and surgical history (p = 0.013). Conclusions: Our findings indicate that the ApaI (rs7975232) and TaqI (rs731236) polymorphisms of the VDR gene are significantly associated with an increased risk of PCa in the Moroccan population. Moreover, ApaI was linked to smoking, while TaqI showed an association with tumor stage and surgical history, suggesting that these variants may influence both genetic predisposition and cancer progression. Original Article Thu, 17 Apr 2025 00:00:00 GMT KawtarNabil, AbdelilahLaraqui, IkramTiabi, Kaoutar AnouarTadlaoui, MohammedMrabti, AhmedAmeur, KhalidEnnibi, MustaphaBenhessou, Moulay MustaphaEnnaji, Thu, 17 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001305 https://www.explorationpub.com/Journals/em/Article/1001307 Aim: This study aimed to evaluate the differential effects of active joint mobilization (AJM) versus traditional passive joint mobilization (PJM) in individuals with chronic ankle instability. We hypothesized that the integration of active components may yield superior outcomes through enhanced proprioceptive feedback and neuromuscular recruitment patterns. Methods: In this single-blind, parallel-group randomized controlled trial, thirty participants with chronic ankle instability were randomly assigned to either AJM (n = 15) or PJM (n = 15) groups. Interventions were administered by certified physical therapists three times per week for four weeks, with each session lasting 10 minutes. Primary outcome measures included the Cumberland Ankle Instability Tool (CAIT) and dorsiflexion range of motion (DFROM). Secondary outcomes focused on neuromuscular control parameters including joint position sense (JPS) and static balance, assessed at baseline and post-intervention. Results: Both groups demonstrated significant within-group improvements in multiple parameters. The PJM group showed significant improvements in CAIT (p < 0.001), DFROM (p < 0.001), and JPS (p < 0.01). Similarly, the AJM group exhibited significant improvements in CAIT (p < 0.01), DFROM (p < 0.001), and JPS (p < 0.001). Between-group comparison revealed no significant differences in any outcome measures (p > 0.05). Conclusions: Both AJM and PJM demonstrated effectiveness in improving functional ankle stability, range of motion, and proprioceptive function in individuals with chronic ankle instability. While both techniques can serve as viable therapeutic approaches, the slightly larger effect sizes observed in AJM for DFROM and proprioceptive function suggest potential additional benefits of active components (ClinicalTrials.gov identifier: NCT04630899). Original Article Thu, 17 Apr 2025 00:00:00 GMT HyunjoongKim, EunsangLee, MingyunKo, Thu, 17 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001307 https://www.explorationpub.com/Journals/em/Article/1001304 Aim: Breast cancer (BC) is the leading cause of female cancer-related death worldwide. The high incidence of BC has sparked interest in the viral agents role in its development. Identifying co-infection involving potential oncogenic viruses, such as human papillomavirus (HPV), Epstein-Barr virus (EBV), mouse mammary tumor virus (MMTV), and Simian virus 40 (SV40), may improve early detection and treatment strategies of BC. However, the involvement of these viral co-infections in invasive breast cancer (IBC) has not been elucidated. Methods: To investigate this eventual co-infection, screening of viral DNAs isolated from 120 fresh IBC tissue biopsies was performed using a polymerase chain reaction. Statistical analysis were conducted to assess the correlation between viral prevalence and IBC clinicopathological features. Results: Our findings revealed the prevalence of EBV (67.1%), HPV (45.7%), MMTV (72.9%), and SV40 (22.9%) in IBC samples. Co-infection rates were as follows: EBV/HPV (17.14%), EBV/MMTV (22.86%), EBV/SV40 (4.28%), and HPV/MMTV (11.43%). Triple infection with EBV, HPV, and MMTV was observed in 5.71% of cases. Statistically significant associations were identified between: EBV and histological grade, tumour size and stage, and progesterone receptor (PR) and estrogen receptor (ER) status; HPV and histological grade, tumour stage, and PR status; MMTV and histological type, as well as PR and ER status; and SV40 and histological grade and PR status. Conclusions: Although the prevalence of HPV, EBV, MMTV, and SV40 coinfection in Moroccan IBC patients is low, their potential synergistic role in breast carcinogenesis needs to be further investigated, in order to identify new etiological factors for BC. Original Article Wed, 16 Apr 2025 00:00:00 GMT Kaoutar AnouarTadlaoui, AmalSouiri, Soukayna AlaouiSosse, KawtarNabil, MustaphaBenhessou, Moulay MustaphaEnnaji, Wed, 16 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001304 https://www.explorationpub.com/Journals/em/Article/1001309 Aim: The present study explored the bone regeneration potential of chitosan-thiocolchicoside-lauric (CTL) nanogel using MG-63 cell lines. The cytocompatibility of CTL nanogel was also studied using osteoblast-like cells (MG-63 cell lines) and zebrafish embryos. Methods: The effect of CTL nanogel on the metabolic and wound-healing activity of MG-63 cells was investigated in the present study. The alkaline phosphatase (ALP) and bone sialoprotein (BSP) activity of CTL nanogel-treated MG-63 cells were assessed using ELISA. RUNX2, ALP, BSP, and COL1A1 gene expression in MG-63 cells were also investigated after treatment with CTL nanogel. Hatching rates and viability of zebrafish embryos treated with different CTL nanogel concentrations were studied. Any developmental toxicity of embryos after treatment with CTL nanogel was also investigated. Results: There was no significant reduction in the proliferation of MG-63 cells when treated with 5–20 μL/mL of CTL nanogel in the MTT assay (p < 0.05). No prominent morphological changes or nuclear abnormalities were found in the MG-63 cells when treated with various concentrations of CTL nanogel compared to the control group. Invitro scratch wound healing assay showed excellent migration of cells and, hence, showed the excellent wound healing ability of CTL nanogel. ELISA showed significant ALP and BSP activity of CTL nanogel-treated MG-63 cells. RUNX2, ALP, BSP, and COL1A1 gene expression in MG-63 cells after treatment with CTL nanogel were significantly increased compared to the control group (p < 0.05). The hatching and viability rates of the embryos increased as the nanogel concentrations decreased, with the highest hatching rate observed at a 5 µL concentration. Developmental toxicity, such as spinal cord bent, tail bent, or yolk sac oedema, was not observed after treatment with CTL nanogel in zebrafish embryos. Conclusions: CTL nanogel can be used in treating bone defects and helping wound healing. The study also suggests that CTL nanogel had a concentration-dependent effect on zebrafish embryos’ viability and hatching rates only in very high concentrations. Original Article Mon, 21 Apr 2025 00:00:00 GMT AmeenaMustafa, Meignana ArumughamIndiran, KarthikeyanRamalingam, ElumalaiPerumal, RajeshkumarShanmugham, Maria MaddalenaMarrapodi, MarcoCicciù, GiuseppeMinervini, Mon, 21 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001309 https://www.explorationpub.com/Journals/em/Article/1001310 Aim: COVID-19, a multisystemic syndrome caused by SARS-CoV-2, often results in long-term complications collectively referred to as long COVID. This study explores the persistence of neurological and otolaryngological symptoms in patients two years after acute infection, with a focus on gender differences and variant-specific effects. Methods: A retrospective follow-up was conducted in January 2024 on 112 patients who had been hospitalized for COVID-19. Patients completed a questionnaire assessing the persistence of neuropsychiatric, otolaryngological, and systemic symptoms. Results: Findings reveal that 18.3% of women reported persistent neuropsychiatric symptoms, such as memory deficits, depression, and concentration issues, compared to 5.7% of men. Otolaryngological symptoms, including anosmia and ageusia, largely resolved, with only 4.5% reporting persistent issues. Symptom persistence was more common in older individuals, women, smokers, and those with severe acute-phase illness. Neuropsychiatric symptoms remain prominent, underscoring the need for targeted long-term care. Conclusions: Vaccination significantly reduces the risk and severity of long COVID, particularly neuropsychiatric symptoms, emphasizing its role in mitigating the long-term burden of SARS-CoV-2. Future research should explore biomolecular markers and imaging techniques to better understand and address these long-term sequelae. Original Article Mon, 21 Apr 2025 00:00:00 GMT WaelAbu Ruqa, ChristianBarbato, AntonioMinni, Mon, 21 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001310 https://www.explorationpub.com/Journals/em/Article/1001311 Aim: The study aimed to determine which right ventricle echocardiography parameters were associated with severe sleep apnea syndrome in heart failure patients with sleep apnea syndrome. Methods: A cross-sectional monocentric study was conducted, including 85 patients with stable heart failure. All patients underwent home respiratory polygraphy and transthoracic echocardiography with evaluation of the right ventricular echocardiographic parameters and sleep apnea syndrome severity. Results: The average age of the population was 69 years. The median left ventricular ejection fraction was 38% (33; 52). Sleep apnea syndrome was diagnosed in 71 patients (83.5%), with obstructive sleep apnea in 50 patients (58.8%) and central sleep apnea in 21 patients (24.7%). Severe sleep apnea syndrome was observed in 31% (n = 22) of patients. In the univariate analysis, right ventricle Tei index with a cutoff value > 0.50 (OR = 3; 95% CI = 1.06–8.56; p = 0.035), right ventricle fractional area change < 40 (OR = 4; 95% CI = 1.38–11; p = 0.09) and right ventricle free wall longitudinal strain with a cut-off value > –17 (OR = 3.5; 95% CI = 1.15–9.41; p = 0.002) increased the risk of having severe sleep apnea syndrome. In the multivariate analysis, the right ventricle free wall longitudinal strain was the only independent predictor for severe sleep apnea syndrome [hazard ratio (HR) = 0.892; 95% CI = 0.816–0.979; p = 0.036]. Conclusions: Right ventricle free wall longitudinal strain seems to be a strong predictor of severe sleep apnea syndrome in patients with stable chronic heart failure and sleep apnea syndrome. Original Article Wed, 23 Apr 2025 00:00:00 GMT SaoussenAntit, FerdaousYangui, MariemLouati, AmineBoufares, SyrineAbdellatif, Mohamed RidhaCharfi, LiliaZakhama, Wed, 23 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001311 https://www.explorationpub.com/Journals/em/Article/1001306 Aim: The pathogenetic mechanisms and predictors of the development of polyposis and hypertrophy of the sinonasal mucosa (SM) in patients with chronic allergic airway inflammation have not been clearly established. The concentration of inflammatory biomarkers in nasal secretions was determined in children and adolescents with a combined course of bronchial asthma (BA) and allergic rhinitis (AR) in the absence or presence of polyposis and hypertrophy of the SM. Methods: A single-centre observational cross-sectional pilot study was conducted. 93 patients with BA aged 8 to 17 years were studied. Total Nasal Symptom Score (TNSS), sinonasal symptoms (SNOT-22), and peak nasal inspiratory flow (PNIF) were assessed. Concentrations of eosinophil cationic protein (ECP), interleukin 4 (IL-4), IL-1, total immunoglobulin E (IgE), and vascular endothelial growth factor (VEGF) in nasal secretions were determined. Results: The levels of ECP, IL-4, and IL-1 in nasal secretions were statistically significantly higher in patients with the presence of polyposis and hypertrophic SM than in those without, amounting to 83.1 [31.4; 166.8] ng/mL for ECP vs. 29.5 [5.3; 49.9] ng/mL, P < 0.001, for IL-4 174.6 [68.6; 325.5] pg/mL vs. 79.5 [42.8; 146.01] pg/mL, P = 0.004, for IL-1 98.7 [33.7; 267.5] pg/mL and 48.8 [9.01; 108.2] pg/mL, P = 0.025. There were no statistically significant differences in IgE and VEGF levels in nasal secretions, all P > 0.05. Parameters such as ECP, IL-4, and IL-1 were found to be significant predictors of polyposis and hypertrophy in the formation of SM. Conclusions: In patients with a combined course of BA and AR, the presence of polyposis and hypertrophy of SM is associated with higher levels of ECP, IL-4, and IL-1 in nasal secretion. This may indicate that pathological remodelling of SM is associated with both the intensity of allergic inflammation and its relationship with local activation of innate immunity. Original Article Thu, 17 Apr 2025 00:00:00 GMT Svetlana ViktorovnaKrasilnikova, Ekaterina IvanovnaKrestova, Tatyana IvanovnaEliseeva, Regina NiyazovnaKhramova, Ksenia ViktorovnaGorbunova, Elena AlekseevnaLeontieva, Dmitry YuryevichOvsyannikov, Natalia AnatolievnaGeppe, Nailya IskhakovnaKubysheva, Thu, 17 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001306 https://www.explorationpub.com/Journals/em/Article/1001312 Aim: This study aimed to investigate the susceptibility patterns of Pseudomonas aeruginosa strains, examine infection characteristics, and evaluate the appropriateness of empiric antibiotic therapy. Additionally, the study sought to identify factors influencing 30-day all-cause mortality in patients with Pseudomonas aeruginosa infections. Methods: This was a retrospective study conducted at Jordan University Hospital from January 2018 to March 2024. Adult patients (≥ 18 years) with confirmed Pseudomonas aeruginosa infections were included. Data were collected from medical records, focusing on demographics, infection characteristics, antibiotic treatment, and outcomes. The susceptibility patterns of Pseudomonas aeruginosa isolates were classified as multidrug-resistant (MDR) or non-MDR. Logistic regression was used to identify factors associated with 30-day mortality. Results: A total of 210 patients were included in the study, with 106 males (50.5%) and 104 females (49.5%). The majority of infections were community-acquired (n = 178, 84.8%), with the respiratory tract being the most common infection site (n = 81, 38.6%). Nearly half of the Pseudomonas aeruginosa isolates were MDR (n = 99, 47.1%). Empiric antibiotic therapy was administered to all patients, with imipenem-cilastatin (55.7%), vancomycin (35.7%), and piperacillin-tazobactam (26.7%) being the most commonly used antibiotics. Of the 210 patients, 32.4% (n = 68) received inappropriate empiric therapy. The 30-day all-cause mortality rate was 4.9% (n = 10). Multivariate analysis revealed that non-localized infections, such as bacteremia and sepsis, were strongly associated with increased mortality [adjusted odds ratio (AOR) = 17.455, P < 0.001]. Conclusions: This study highlights the high prevalence of MDR Pseudomonas aeruginosa infections, especially in community-acquired cases, and emphasizes the need for improved antimicrobial stewardship. The significant proportion of patients (32.4%) receiving inappropriate empiric therapy calls for better guidance in antibiotic prescribing practices. The key predictor of mortality was infection localization, indicating the importance of early intervention for systemic infections to reduce mortality rates. Original Article Thu, 24 Apr 2025 00:00:00 GMT SavanaSobh, RaniaItani, KhawlaAbu Hammour, Rana K.Abu-Farha, Thu, 24 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001312 https://www.explorationpub.com/Journals/em/Article/1001313 We report a rare case of a female patient with multiple rheumatological conditions. The patient initially presented with periodic, diffuse abdominal pain. This complaint was not fully investigated because polyarthritic symptoms became the predominant ones. This led to the diagnosis of rheumatoid arthritis. Afterward, the patient complained of xerostomia, xerophthalmia, and diffuse rash. After investigations, she was diagnosed with Sjögren’s syndrome. Suspecting a case of methotrexate-induced vasculitis, her initial prescription was changed to azathioprine and then to etanercept. Eventually, her persistent abdominal pain, combined with her Armenian origin, prompted her physician to order a genetic analysis of the MEFV gene, which revealed the V726A/P369S mutation, giving rise to the diagnosis of Familial Mediterranean Fever. In her routine follow-up, the patient was in a stable condition, adherent to the medications, and showed improvement in her symptoms. Therefore, this case shows the importance of early genetic testing in similar cases, which in turn will allow timely diagnosis and treatment. Case Report Sun, 27 Apr 2025 00:00:00 GMT FadiAltamimi, RoupenAvinguolo, ArshakShahenyan, KnarikGinosyan, YasmeenAlabdallat, Sun, 27 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001313 https://www.explorationpub.com/Journals/em/Article/1001315 The cardiovascular system remains vulnerable to a multitude of threats, including infections, inflammation, and oxidative stress. These factors contribute significantly to the development and progression of cardiovascular diseases, a pressing global health concern. Historically, research into natural medicines has primarily focused on isolated compounds. However, complex natural entities like essential oils, rich in diverse chemical constituents, offer superior therapeutic potential. We discuss here how their inherent variability can lead to unpredictable synergistic and antagonistic effects, hindering consistent therapeutic outcomes. This inconsistency is particularly problematic in addressing the rising incidence of perioperative infections and the need to combat radical-mediated damage and subclinical inflammation. This scoping review departs from the hypothesis “Can we leverage complex natural products for the discovery of new clinical approaches to cardiovascular diseases encompassing inflammation and infection?”. Therefore, we delve into the potential of complex natural products, particularly essential oils, in preventing cardiovascular infections and mitigating oxidative damage, emphasizing the crucial role of artificial neural networks (ANNs) in advancing this field. The review emphasizes the need for multidisciplinary collaboration to generate quality data for effective ANN analysis, envisioning future integration of omics technologies with ANNs for more precise predictions of natural product activities. It addresses challenges in translating AI-designed essential oils to clinical practice, including intellectual property protection and standardization issues due to regional variability, suggesting a potential role for the World Health Organization in establishing guidelines for essential oil specifications to ensure consistent efficacy while enabling global accessibility. The author concludes by stressing the need to address ethical considerations at the intersection of technology, science, and clinical practice, particularly regarding the proprietary status of essential oils versus making them freely available worldwide. Review Mon, 28 Apr 2025 00:00:00 GMT Jose M.Prieto-Garcia, Mon, 28 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001315 https://www.explorationpub.com/Journals/em/Article/1001316 Background: Early detection of precancerous oral lesions is crucial for preventing oral cancer. Traditional visual inspections have limitations, prompting the development of advanced technologies to improve detection accuracy. The study focused on evaluating and summarizing recent advancements in optical, molecular, and digital technologies used for the identification of oral potentially malignant disorders (OPMDs). Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, focusing on studies published in English between 2014 and 2024. The search targeted pioneering research addressing key challenges in OPMD detection. Selection criteria prioritized innovative approaches for identifying potentially malignant oral lesions. Results: The initial search yielded 359 studies, with 10 meeting the inclusion criteria for in-depth analysis. These studies highlight emerging technologies that enhance early detection, including molecular biomarkers for analyzing genetic and protein alterations, liquid biopsy for detecting circulating tumor DNA (ctDNA), and AI-assisted diagnostics. Additionally, fluorescence spectroscopy and optical coherence tomography (OCT) improve detection accuracy, enabling early interventions and better patient outcomes. Conclusions: The systematic review underscores the growing significance of innovative technologies in the early identification of OPMDs. Advances in optical methods such as fluorescence spectroscopy and OCT, molecular techniques including biomarker analysis and liquid biopsy, and digital innovations like AI-driven diagnostics offer substantial improvements over conventional visual inspection. These technologies not only enhance detection accuracy but also hold promise for earlier diagnosis and improved clinical outcomes. Continued research and validation are essential to translate these emerging tools into routine clinical practice, ensuring timely intervention and effective prevention of oral cancer. Systematic Review Mon, 28 Apr 2025 00:00:00 GMT SuprajaSalwaji, Mohan KumarPasupuleti, RavikanthManyam, SwethaPasupuleti, HandeUzunçıbuk, DianaRusso, GabrieleCervino, Maria MaddalenaMarrapodi, GiuseppeMinervini, Mon, 28 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001316 https://www.explorationpub.com/Journals/em/Article/1001314 The interaction between cancer and coronavirus disease 2019 (COVID-19) poses significant challenges, particularly for immunocompromised individuals who are at heightened risk for acute infections and long-term complications. The pandemic has exacerbated existing vulnerabilities in cancer care by disrupting treatment protocols and delaying diagnoses, leading to worsened health outcomes. This article emphasizes the importance of investigating the potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on cancer progression and highlights the need for effective strategies to protect this high-risk population. Long-term health consequences, including the emergence of long COVID, further emphasize the need for ongoing surveillance and comprehensive healthcare planning for cancer patients during and after pandemics. A multifaceted approach is essential, incorporating vaccination, timely therapeutic interventions, and sustained support for patients with lingering symptoms. This article also discusses and urges continued research into the oncogenic risks associated with SARS-CoV-2, which is crucial for enhancing our understanding of the broader health implications of COVID-19 and for informing public health strategies aimed at safeguarding cancer patients in future pandemics. Moreover, effective data collection and the development of refined clinical guidelines are vital for improving patient outcomes and preparing healthcare systems to support cancer patients during crises. Additionally, this article discusses the importance of investigating the mechanisms by which SARS-CoV-2 may increase cancer susceptibility, including chronic inflammation, cellular senescence, and immune dysregulation. Understanding these mechanisms is crucial for elucidating the virus’s long-term oncogenic potential, particularly among cancer survivors and individuals with chronic infections. Ensuring continuity and resilience in cancer care during global crises requires strategies to mitigate healthcare disruptions, enhance access to screenings and treatments, and address the specific challenges faced by cancer patients experiencing long COVID. Review Tue, 29 Apr 2025 00:00:00 GMT Moawiah MNaffaa, Ola AAl-Ewaidat, Tue, 29 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/em/Article/1001314