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.
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.
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.
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.
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.
Read less.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.
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.
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.
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).
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.
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.
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).
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).
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.
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.
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).
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).
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.
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%.
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).
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).
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.
Read less.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.
Read less.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.
Read less.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.
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.
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.
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.
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.
Read less.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.
Read less.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.
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.
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.
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.
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.
Read less.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.
Read less.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.
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.
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.
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.
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.
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.
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.
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.
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.
Read less.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.
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.
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%).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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).
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.
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.
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).
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).
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.
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.
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).
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).
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.
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.
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).
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).
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.
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.
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).
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).
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.
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%.
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).
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).
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.
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%.
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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%).
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.
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.
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.
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%).
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.