Interstitial lung disease (ILD) is one of the most important extra-articular manifestations of rheumatoid arthritis (RA) due to its associated significant mortality. The availability of pharmacological treatments capable of slowing its progression, especially when initiated early, makes early diagnosis an essential part of its management. The low sensitivity of chest X-ray or lung function tests to identify RA-ILD in the early stages of the disease, together with the cost, accessibility, and ionizing radiation limitations of high-resolution computed tomography (HRCT), especially when serial screening or follow-up studies are required, has prompted the study of lung ultrasound (LUS) as an additional aid for the screening, diagnosis, and/or follow-up of RA-ILD. Based on the safety, low cost, and accessibility of LUS, and the encouraging results of research into this technique in ILD associated with systemic sclerosis, progress has been made in its validation process with research addressing aspects such as its accuracy, feasibility, and reliability. Negative predictive value and sensitivity values exceeding 80–90% have been reported, suggesting its potential utility. Feasibility has been suggested since LUS scan can be performed in less than 10 minutes, and intra- and inter-observer or examiner reliability shows values in the good to excellent range. However, there are still aspects that require further investigation, such as the standardization of the LUS scanning protocol or the requirements to ensure an effective learning curve before applying the technique in clinical practice. It is necessary to recognize the inherent limitations of LUS and understand that it should be considered a tool to aid in the early identification of patients who require HRCT, which is currently the diagnostic gold standard.
Interstitial lung disease (ILD) is one of the most important extra-articular manifestations of rheumatoid arthritis (RA) due to its associated significant mortality. The availability of pharmacological treatments capable of slowing its progression, especially when initiated early, makes early diagnosis an essential part of its management. The low sensitivity of chest X-ray or lung function tests to identify RA-ILD in the early stages of the disease, together with the cost, accessibility, and ionizing radiation limitations of high-resolution computed tomography (HRCT), especially when serial screening or follow-up studies are required, has prompted the study of lung ultrasound (LUS) as an additional aid for the screening, diagnosis, and/or follow-up of RA-ILD. Based on the safety, low cost, and accessibility of LUS, and the encouraging results of research into this technique in ILD associated with systemic sclerosis, progress has been made in its validation process with research addressing aspects such as its accuracy, feasibility, and reliability. Negative predictive value and sensitivity values exceeding 80–90% have been reported, suggesting its potential utility. Feasibility has been suggested since LUS scan can be performed in less than 10 minutes, and intra- and inter-observer or examiner reliability shows values in the good to excellent range. However, there are still aspects that require further investigation, such as the standardization of the LUS scanning protocol or the requirements to ensure an effective learning curve before applying the technique in clinical practice. It is necessary to recognize the inherent limitations of LUS and understand that it should be considered a tool to aid in the early identification of patients who require HRCT, which is currently the diagnostic gold standard.
Occupational allergens are an important cause of diseases emerging in the workplace, both indoor and outdoor, causing conditions such as allergic asthma, dermatitis, and rhinitis. Numerous national and international institutions focus on sensitizing agents able to induce allergies in workplaces, which are also considered by the International Classification of Diseases (ICD)-11, underlining their increasing worldwide importance. There is thus the need to develop and implement new, multidisciplinary approaches to study and monitor these agents, taking into account different sources of exposure, environmental concentrations, co-factors of exposure, and individual susceptibility. This includes the integration between traditional and innovative methodologies applied to environmental and biological matrices, as well as the use of “omic” techniques. In this picture, information, training, and communication emerge as fundamental for workers. This kind of approach will permit us to attain a better management of exposure to allergens in the workplace, improving the well-being of workers worldwide.
Occupational allergens are an important cause of diseases emerging in the workplace, both indoor and outdoor, causing conditions such as allergic asthma, dermatitis, and rhinitis. Numerous national and international institutions focus on sensitizing agents able to induce allergies in workplaces, which are also considered by the International Classification of Diseases (ICD)-11, underlining their increasing worldwide importance. There is thus the need to develop and implement new, multidisciplinary approaches to study and monitor these agents, taking into account different sources of exposure, environmental concentrations, co-factors of exposure, and individual susceptibility. This includes the integration between traditional and innovative methodologies applied to environmental and biological matrices, as well as the use of “omic” techniques. In this picture, information, training, and communication emerge as fundamental for workers. This kind of approach will permit us to attain a better management of exposure to allergens in the workplace, improving the well-being of workers worldwide.
Work-related musculoskeletal disorders (WMSDs) are a major occupational health burden, yet early functional alterations are often difficult to capture with symptom-only screening or with predominantly structural imaging. Infrared thermography (IRT) provides a noncontact, nonionizing, physiologically grounded readout of superficial heat exchange that is strongly influenced by microperfusion and autonomic vasomotor control. We conducted an integrative narrative review with traceable study-level compilation to synthesize physiological foundations for thermal-signal interpretation, minimum requirements for acquisition standardization and Quality Control, and occupational applications for screening, risk characterization, and longitudinal monitoring, including multimodal integration. The final included corpus comprised 247 studies spanning diverse designs and contexts, with substantial heterogeneity in devices, regions of interest (ROIs), environmental conditions, thermal metrics, and reporting completeness. Across the evidence, interpretability was consistently dependent on protocol stability and on ROI-based, within-subject metrics [bilateral asymmetry, task-induced temperature difference (ΔT), and recovery dynamics] rather than isolated absolute thresholds. Occupational applications have most often targeted repetitive upper-limb demands, computer-based work, and cold challenge/rewarming paradigms in vibration-exposed populations. We provide an operational checklist aligned with guideline recommendations and propose a pragmatic multimodal workflow integrating IRT with functional measures [surface electromyography (sEMG), strength], structural/perfusion modalities (ultrasonography), and patient-reported outcomes. Future priorities include multicenter harmonization, occupation- and task-specific reference profiles, and prospective validation of decision rules under real-world conditions.
Work-related musculoskeletal disorders (WMSDs) are a major occupational health burden, yet early functional alterations are often difficult to capture with symptom-only screening or with predominantly structural imaging. Infrared thermography (IRT) provides a noncontact, nonionizing, physiologically grounded readout of superficial heat exchange that is strongly influenced by microperfusion and autonomic vasomotor control. We conducted an integrative narrative review with traceable study-level compilation to synthesize physiological foundations for thermal-signal interpretation, minimum requirements for acquisition standardization and Quality Control, and occupational applications for screening, risk characterization, and longitudinal monitoring, including multimodal integration. The final included corpus comprised 247 studies spanning diverse designs and contexts, with substantial heterogeneity in devices, regions of interest (ROIs), environmental conditions, thermal metrics, and reporting completeness. Across the evidence, interpretability was consistently dependent on protocol stability and on ROI-based, within-subject metrics [bilateral asymmetry, task-induced temperature difference (ΔT), and recovery dynamics] rather than isolated absolute thresholds. Occupational applications have most often targeted repetitive upper-limb demands, computer-based work, and cold challenge/rewarming paradigms in vibration-exposed populations. We provide an operational checklist aligned with guideline recommendations and propose a pragmatic multimodal workflow integrating IRT with functional measures [surface electromyography (sEMG), strength], structural/perfusion modalities (ultrasonography), and patient-reported outcomes. Future priorities include multicenter harmonization, occupation- and task-specific reference profiles, and prospective validation of decision rules under real-world conditions.
Bisoprolol fumarate (BF), commonly prescribed for cardiovascular conditions, is usually split to achieve specific doses. This study evaluated the effects of tablet splitting on the quality parameters of scored BF tablets from three different brands marketed in Saudi Arabia.
The products were evaluated for weight variation, content uniformity, and dissolution for intact and split tablets. A UPLC-sensitive assay was used for drug quantification.
The results showed that all products lost less than 3% of its weight upon splitting, meeting the USP requirements. Content uniformity was between 85% and 115% for all products, complying with pharmacopoeial standards. Dissolution studies showed some variation between intact and split tablets. The f2 similarity factor was calculated to compare the dissolution profiles of BF from both forms. The f2 values showed a similar dissolution profile for the innovator product (f2 was 62.53), but dissimilar profiles for Generic-1 and -2 (f2 values were 48.90 and 34.43, respectively).
These results should be taken into consideration by healthcare professionals to avoid sub-therapeutic or toxic effects resulting from tablet splitting.
Bisoprolol fumarate (BF), commonly prescribed for cardiovascular conditions, is usually split to achieve specific doses. This study evaluated the effects of tablet splitting on the quality parameters of scored BF tablets from three different brands marketed in Saudi Arabia.
The products were evaluated for weight variation, content uniformity, and dissolution for intact and split tablets. A UPLC-sensitive assay was used for drug quantification.
The results showed that all products lost less than 3% of its weight upon splitting, meeting the USP requirements. Content uniformity was between 85% and 115% for all products, complying with pharmacopoeial standards. Dissolution studies showed some variation between intact and split tablets. The f2 similarity factor was calculated to compare the dissolution profiles of BF from both forms. The f2 values showed a similar dissolution profile for the innovator product (f2 was 62.53), but dissimilar profiles for Generic-1 and -2 (f2 values were 48.90 and 34.43, respectively).
These results should be taken into consideration by healthcare professionals to avoid sub-therapeutic or toxic effects resulting from tablet splitting.
Glioblastoma (GBM), a rare, highly aggressive and chemoresistant brain cancer, exhibits profound metabolic plasticity that relies, in part, on aberrant transforming growth factor-β (TGF-β) signaling. Such plasticity was recently associated with TGF-β-regulated apoptosis and autophagy. Here, we questioned whether TGF-β-regulated apoptotic/autophagic phenotypes are recapitulated in a preclinical in vitro 3D spheroid culture model of human U87 GBM-derived cells, and how metabolic alterations affect such phenotypes.
3D U87 spheroids were cultured using the hanging drop method. Western blotting was used to assess protein expression, while RT-qPCR was used to assess gene expression levels.
3D spheroids exhibited decreased AKT phosphorylation, and increased TGF-β, fibronectin, and Smad2 phosphorylation, indicative of both cell death signaling and epithelial-mesenchymal transition molecular signatures. 2-Deoxy-D-glucose (2DG), a glycolytic inhibitor, depleted ATP dose-dependently (30–300 μM) and prevented those increases both at the protein and transcriptional levels. This was also observed in 3D spheroids upon TGF-β transient siRNA-mediated silencing or when TGF-βR1 kinase activity was inhibited by galunisertib. Transcriptomic profiling revealed shared upregulation of apoptosis-related (BCL2, CASP7, FAS, FASLG, GADD45A) and autophagy-related (ATG7, ATG16L1, IRGM, PIK3C3, ULK1) genes in response to TGF-β or upon 3D spheroid formation. 2DG, transient silencing of TGF-β, or galunisertib treatment prevented these increases.
3D spheroids require ATP and a TGF-β/TGF-βR1 autocrine signaling axis to recapitulate the apoptosis/autophagy phenotypes. Combining glycolysis inhibition with TGF-β signaling inhibition could offer a promising therapeutic strategy for this rare and lethal brain cancer.
Glioblastoma (GBM), a rare, highly aggressive and chemoresistant brain cancer, exhibits profound metabolic plasticity that relies, in part, on aberrant transforming growth factor-β (TGF-β) signaling. Such plasticity was recently associated with TGF-β-regulated apoptosis and autophagy. Here, we questioned whether TGF-β-regulated apoptotic/autophagic phenotypes are recapitulated in a preclinical in vitro 3D spheroid culture model of human U87 GBM-derived cells, and how metabolic alterations affect such phenotypes.
3D U87 spheroids were cultured using the hanging drop method. Western blotting was used to assess protein expression, while RT-qPCR was used to assess gene expression levels.
3D spheroids exhibited decreased AKT phosphorylation, and increased TGF-β, fibronectin, and Smad2 phosphorylation, indicative of both cell death signaling and epithelial-mesenchymal transition molecular signatures. 2-Deoxy-D-glucose (2DG), a glycolytic inhibitor, depleted ATP dose-dependently (30–300 μM) and prevented those increases both at the protein and transcriptional levels. This was also observed in 3D spheroids upon TGF-β transient siRNA-mediated silencing or when TGF-βR1 kinase activity was inhibited by galunisertib. Transcriptomic profiling revealed shared upregulation of apoptosis-related (BCL2, CASP7, FAS, FASLG, GADD45A) and autophagy-related (ATG7, ATG16L1, IRGM, PIK3C3, ULK1) genes in response to TGF-β or upon 3D spheroid formation. 2DG, transient silencing of TGF-β, or galunisertib treatment prevented these increases.
3D spheroids require ATP and a TGF-β/TGF-βR1 autocrine signaling axis to recapitulate the apoptosis/autophagy phenotypes. Combining glycolysis inhibition with TGF-β signaling inhibition could offer a promising therapeutic strategy for this rare and lethal brain cancer.
The rising consumption of convenience foods has increased demand for nutritionally balanced snacks such as granola bars. Traditional formulations rely on sugar as a binder, which may raise health concerns. This study investigates the use of fructo-oligosaccharides (FOS), a low-calorie prebiotic sweetener, as a substitute for glucose syrup to enhance the nutritional quality of granola bars.
Five granola bars with different formulations were prepared by replacing sugar with FOS at varying substitution levels (0%, 25%, 50%, 75%, and 100%). The bars were evaluated for proximate composition, physicochemical properties (colour, pH, water activity, and texture), and sensory attributes.
Increasing FOS levels significantly increased moisture and fiber content, while moderately reducing sugar, fat, and energy values. Higher FOS incorporation also slightly increased pH, reduced water activity, and produced lighter and less yellow bars. Sensory evaluation indicated that all formulations were acceptable, with the 75% FOS formulation receiving the highest preference scores.
The results from this study suggest that FOS syrup is an effective alternative to glucose syrup in granola bars, enhancing nutritional value without compromising sensory quality. Partial substitution (up to 75%) optimizes consumer acceptability while providing a functional, low-calorie, and fiber-enriched snack option.
The rising consumption of convenience foods has increased demand for nutritionally balanced snacks such as granola bars. Traditional formulations rely on sugar as a binder, which may raise health concerns. This study investigates the use of fructo-oligosaccharides (FOS), a low-calorie prebiotic sweetener, as a substitute for glucose syrup to enhance the nutritional quality of granola bars.
Five granola bars with different formulations were prepared by replacing sugar with FOS at varying substitution levels (0%, 25%, 50%, 75%, and 100%). The bars were evaluated for proximate composition, physicochemical properties (colour, pH, water activity, and texture), and sensory attributes.
Increasing FOS levels significantly increased moisture and fiber content, while moderately reducing sugar, fat, and energy values. Higher FOS incorporation also slightly increased pH, reduced water activity, and produced lighter and less yellow bars. Sensory evaluation indicated that all formulations were acceptable, with the 75% FOS formulation receiving the highest preference scores.
The results from this study suggest that FOS syrup is an effective alternative to glucose syrup in granola bars, enhancing nutritional value without compromising sensory quality. Partial substitution (up to 75%) optimizes consumer acceptability while providing a functional, low-calorie, and fiber-enriched snack option.
Chamomile (Matricaria recutita) is an edible flowering herb widely valued for its medicinal, aromatic, and technological attributes, making it an important raw material in contemporary food applications. This review evaluates the chemical profile, bioactivity, and functional health potential of chamomile extract based on current scientific evidence. The extract contains diverse bioactive constituents, particularly flavonoids, terpenoids, and phenolic compounds, which are responsible for its strong antioxidant, antimicrobial, and anti-inflammatory properties. Owing to these characteristics and its pleasant sensory profile, chamomile extract has been incorporated into various functional foods, especially fermented and probiotic products such as herbal beverages and chamomile-enriched yogurt. Experimental findings from in vitro and in vivo studies indicate that chamomile may suppress cancer cell growth, reduce anxiety symptoms, promote gastrointestinal health, support cardiovascular function, and modulate immune responses. Beyond its therapeutic relevance, chamomile extract also serves as a natural substitute for synthetic preservatives and additives, aligning with increasing consumer demand for clean-label and plant-based ingredients. Its multifunctional properties contribute to improved food stability, safety, and shelf life while enhancing nutritional value. In addition, chamomile imparts a characteristic floral aroma, mild taste, and appealing color, which further support consumer acceptance. Collectively, chamomile extract demonstrates substantial promise as a natural functional ingredient, nutraceutical component, and bio-preservative for the development of health-oriented and technologically advanced food products, highlighting its expanding role in human nutrition and future food innovation.
Chamomile (Matricaria recutita) is an edible flowering herb widely valued for its medicinal, aromatic, and technological attributes, making it an important raw material in contemporary food applications. This review evaluates the chemical profile, bioactivity, and functional health potential of chamomile extract based on current scientific evidence. The extract contains diverse bioactive constituents, particularly flavonoids, terpenoids, and phenolic compounds, which are responsible for its strong antioxidant, antimicrobial, and anti-inflammatory properties. Owing to these characteristics and its pleasant sensory profile, chamomile extract has been incorporated into various functional foods, especially fermented and probiotic products such as herbal beverages and chamomile-enriched yogurt. Experimental findings from in vitro and in vivo studies indicate that chamomile may suppress cancer cell growth, reduce anxiety symptoms, promote gastrointestinal health, support cardiovascular function, and modulate immune responses. Beyond its therapeutic relevance, chamomile extract also serves as a natural substitute for synthetic preservatives and additives, aligning with increasing consumer demand for clean-label and plant-based ingredients. Its multifunctional properties contribute to improved food stability, safety, and shelf life while enhancing nutritional value. In addition, chamomile imparts a characteristic floral aroma, mild taste, and appealing color, which further support consumer acceptance. Collectively, chamomile extract demonstrates substantial promise as a natural functional ingredient, nutraceutical component, and bio-preservative for the development of health-oriented and technologically advanced food products, highlighting its expanding role in human nutrition and future food innovation.
Immuno-materials, which represent a confluence of immunology and materials science, are dramatically transforming the fields of healthcare. Through the targeted modulation of immune responses, these innovative materials offer promising avenues for advancements in vaccine development, immunotherapy, tissue engineering, and diagnostics. This review examines the fundamental principles of immuno-materials, elucidating key concepts and methodologies pertinent to their development. We investigate strategies for engineering materials that can elicit customized immune responses, capable of both stimulation and suppression, and we discuss their potential roles as adjuvants, carriers, or scaffolds. Furthermore, we address the challenges and opportunities associated with the clinical translation of these materials, emphasizing the critical importance of biocompatibility, safety, and efficacy. This review aims to critically evaluate and contextualize the transformative potential of immuno-materials, mapping their journey from laboratory design to proven clinical applications in enhancing human health.
Immuno-materials, which represent a confluence of immunology and materials science, are dramatically transforming the fields of healthcare. Through the targeted modulation of immune responses, these innovative materials offer promising avenues for advancements in vaccine development, immunotherapy, tissue engineering, and diagnostics. This review examines the fundamental principles of immuno-materials, elucidating key concepts and methodologies pertinent to their development. We investigate strategies for engineering materials that can elicit customized immune responses, capable of both stimulation and suppression, and we discuss their potential roles as adjuvants, carriers, or scaffolds. Furthermore, we address the challenges and opportunities associated with the clinical translation of these materials, emphasizing the critical importance of biocompatibility, safety, and efficacy. This review aims to critically evaluate and contextualize the transformative potential of immuno-materials, mapping their journey from laboratory design to proven clinical applications in enhancing human health.
Paediatric orthopaedics has evolved as a specialized branch of orthopaedics, reflecting the understanding of child development and paediatric musculoskeletal disorders. The push for creative ideas and innovations has expanded its scope and indications to a wide group of musculoskeletal disorders in children. This review discusses some of the most impactful innovations of the late 20th and 21st centuries in the field of paediatric orthopaedic surgery and highlights their relevance in the management of complex problems. It includes their evolution over time, current strengths and challenges, and the scope of further improvement in the future. In addition, it discusses the future perspective and possibilities for similar groundbreaking innovations in the field of paediatric orthopaedics.
Paediatric orthopaedics has evolved as a specialized branch of orthopaedics, reflecting the understanding of child development and paediatric musculoskeletal disorders. The push for creative ideas and innovations has expanded its scope and indications to a wide group of musculoskeletal disorders in children. This review discusses some of the most impactful innovations of the late 20th and 21st centuries in the field of paediatric orthopaedic surgery and highlights their relevance in the management of complex problems. It includes their evolution over time, current strengths and challenges, and the scope of further improvement in the future. In addition, it discusses the future perspective and possibilities for similar groundbreaking innovations in the field of paediatric orthopaedics.
The biopsychosocial model is the prevailing framework for chronic orofacial pain (COP). While COP is a heterogeneous clinical entity involving nociceptive and neuropathic components, it is increasingly defined by its nociplastic features—a systemic, non-nociceptive state in which psychological factors significantly influence symptoms. Current research frequently suffers from the conflation of constructs. Psychosocial predictors (e.g., self-efficacy) and outcome measures (e.g., pain interference) are often conceptually inseparable. To advance beyond this, we advocate for the integration of the brain-heart axis (BHA). The BHA provides objective, quantifiable markers of autonomic nervous system (ANS) dysregulation, the physical manifestation of chronic stress rooted in large-scale brain network imbalance. The present study proposes a theoretical framework in which psychological distress is reflected in corrected QT interval (QTc) changes, while low self-efficacy is mirrored by reduced heart rate variability (HRV). This integration is supported by the neurochemical roles of N-methyl-D-aspartate (NMDA) receptors in central sensitization and dopamine D2 receptor dysfunction in the basal ganglia. The present paper delineates a framework for research and clinical implementation within advanced dental training.
The biopsychosocial model is the prevailing framework for chronic orofacial pain (COP). While COP is a heterogeneous clinical entity involving nociceptive and neuropathic components, it is increasingly defined by its nociplastic features—a systemic, non-nociceptive state in which psychological factors significantly influence symptoms. Current research frequently suffers from the conflation of constructs. Psychosocial predictors (e.g., self-efficacy) and outcome measures (e.g., pain interference) are often conceptually inseparable. To advance beyond this, we advocate for the integration of the brain-heart axis (BHA). The BHA provides objective, quantifiable markers of autonomic nervous system (ANS) dysregulation, the physical manifestation of chronic stress rooted in large-scale brain network imbalance. The present study proposes a theoretical framework in which psychological distress is reflected in corrected QT interval (QTc) changes, while low self-efficacy is mirrored by reduced heart rate variability (HRV). This integration is supported by the neurochemical roles of N-methyl-D-aspartate (NMDA) receptors in central sensitization and dopamine D2 receptor dysfunction in the basal ganglia. The present paper delineates a framework for research and clinical implementation within advanced dental training.
Climate change is reshaping the aeroallergen landscape, with rising temperatures, elevated CO2, shifting precipitation, and land-use change extending pollen seasons, increasing pollen loads and allergenicity, and expanding the geographic range of allergenic plants. These changes are accompanied by escalating air pollution from fossil fuel combustion and wildfires that act as an adjuvant with co-exposure with allergen exacerbate allergic airway disease. Vulnerable populations—particularly those in socioeconomically disadvantaged and marginalized communities in the US—experience disproportionate exposure to pollutants and allergens due to structural inequities that result in some populations being exposed to more environmental hazards than other groups. Climate-amplified aeroallergen exposure and air pollution are associated with higher sensitization, symptom burden, exacerbations, and healthcare use. Structural inequities magnify exposures to allergens and air pollution, while also influencing the social environment through concentration of poverty and diminished access to resources. This review synthesizes evidence linking climate change-related effects on aeroallergens and air pollution with allergic disease risk and the modification of this relationship by social vulnerability, with a focus on Europe and North America. We also highlight established and emerging strategies to mitigate the effects of climate change on allergic disease prevalence and morbidity, including anticipatory guidance, digital forecasting, community adaptation measures, and local, regional, and national policies that promote responsible land use, healthy housing, and equity-focused public health initiatives.
Climate change is reshaping the aeroallergen landscape, with rising temperatures, elevated CO2, shifting precipitation, and land-use change extending pollen seasons, increasing pollen loads and allergenicity, and expanding the geographic range of allergenic plants. These changes are accompanied by escalating air pollution from fossil fuel combustion and wildfires that act as an adjuvant with co-exposure with allergen exacerbate allergic airway disease. Vulnerable populations—particularly those in socioeconomically disadvantaged and marginalized communities in the US—experience disproportionate exposure to pollutants and allergens due to structural inequities that result in some populations being exposed to more environmental hazards than other groups. Climate-amplified aeroallergen exposure and air pollution are associated with higher sensitization, symptom burden, exacerbations, and healthcare use. Structural inequities magnify exposures to allergens and air pollution, while also influencing the social environment through concentration of poverty and diminished access to resources. This review synthesizes evidence linking climate change-related effects on aeroallergens and air pollution with allergic disease risk and the modification of this relationship by social vulnerability, with a focus on Europe and North America. We also highlight established and emerging strategies to mitigate the effects of climate change on allergic disease prevalence and morbidity, including anticipatory guidance, digital forecasting, community adaptation measures, and local, regional, and national policies that promote responsible land use, healthy housing, and equity-focused public health initiatives.
Microbial metabolites are now recognized as central mediators of host–microbe communication that shape intestinal immune homeostasis and influence the development of inflammatory gastrointestinal diseases. The objective of this review is to synthesize current mechanistic evidence on how microbiota-derived metabolites regulate epithelial and immune functions in the gut, with a focus on metabolite-driven inflammatory pathways. In the healthy intestine, short-chain fatty acids (SCFAs), indole derivatives, secondary bile acids, and polyamines support epithelial integrity, regulate mucosal immunity, and maintain metabolic balance. SCFAs, particularly butyrate, attenuate inflammation by serving as an energy source for colonocytes, inhibiting histone deacetylases, activating G protein-coupled receptors (GPCRs; GPR41, GPR43, GPR109A), and reinforcing epithelial barrier function. In parallel, microbial tryptophan metabolites such as indole-3-propionic acid and indole-3-aldehyde activate aryl hydrocarbon receptor signaling, promoting IL-22 production, antimicrobial peptide expression, and Th17–Treg balance. In inflammatory bowel disease, dysbiosis disrupts these protective pathways, leading to depletion of SCFA- and indole-producing taxa and accumulation of pro-inflammatory metabolites such as succinate. These metabolic shifts impair epithelial-immune crosstalk, amplify NF-κB-dependent inflammation, and compromise mucosal repair. Therapeutic strategies targeting microbial metabolites, including precision prebiotics, next-generation probiotics, engineered microbial consortia, and postbiotics, show translational promise. However, their clinical application remains constrained by interindividual variability, incomplete causal resolution, and challenges in targeted delivery. Integrative multi-omics approaches and mechanistically informed models are therefore essential to advance metabolite-based diagnostics and therapies for gut inflammation.
Microbial metabolites are now recognized as central mediators of host–microbe communication that shape intestinal immune homeostasis and influence the development of inflammatory gastrointestinal diseases. The objective of this review is to synthesize current mechanistic evidence on how microbiota-derived metabolites regulate epithelial and immune functions in the gut, with a focus on metabolite-driven inflammatory pathways. In the healthy intestine, short-chain fatty acids (SCFAs), indole derivatives, secondary bile acids, and polyamines support epithelial integrity, regulate mucosal immunity, and maintain metabolic balance. SCFAs, particularly butyrate, attenuate inflammation by serving as an energy source for colonocytes, inhibiting histone deacetylases, activating G protein-coupled receptors (GPCRs; GPR41, GPR43, GPR109A), and reinforcing epithelial barrier function. In parallel, microbial tryptophan metabolites such as indole-3-propionic acid and indole-3-aldehyde activate aryl hydrocarbon receptor signaling, promoting IL-22 production, antimicrobial peptide expression, and Th17–Treg balance. In inflammatory bowel disease, dysbiosis disrupts these protective pathways, leading to depletion of SCFA- and indole-producing taxa and accumulation of pro-inflammatory metabolites such as succinate. These metabolic shifts impair epithelial-immune crosstalk, amplify NF-κB-dependent inflammation, and compromise mucosal repair. Therapeutic strategies targeting microbial metabolites, including precision prebiotics, next-generation probiotics, engineered microbial consortia, and postbiotics, show translational promise. However, their clinical application remains constrained by interindividual variability, incomplete causal resolution, and challenges in targeted delivery. Integrative multi-omics approaches and mechanistically informed models are therefore essential to advance metabolite-based diagnostics and therapies for gut inflammation.
Peripheral neuropathy is a frequent but often under-recognized extra-articular manifestation of rheumatoid arthritis (RA), frequently linked to chronic systemic inflammation. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a simple marker of systemic inflammatory burden. This study aimed to investigate the association between NLR and peripheral neuropathy in RA.
This cross-sectional study included 230 RA patients. Peripheral neuropathy was identified through clinical evaluation and nerve conduction studies. Demographic and clinical data, serological status, disease activity [28-joint Disease Activity Score (DAS28)], inflammatory markers, and complete blood counts were obtained. NLR was calculated from absolute neutrophil and lymphocyte counts. Multivariable logistic regression was used to identify factors associated with peripheral neuropathy. Discriminatory performance of NLR was evaluated using receiver operating characteristic (ROC) curve analysis.
Peripheral neuropathy was present in 93 of 230 patients (40.4%). Patients with neuropathy exhibited significantly higher NLR compared with those without neuropathy (median 3.8 vs. 2.3; P < 0.001). In multivariable logistic regression adjusting for age, disease duration, disease activity (DAS28), C-reactive protein (CRP), serological status, and glucocorticoid use, elevated NLR remained independently associated with the presence of peripheral neuropathy [adjusted odds ratio (OR) = 1.92, 95% confidence interval (CI): 1.48–2.49; P < 0.001]. Other factors significantly associated with neuropathy included older age, longer disease duration, higher DAS28, and seropositive status. CRP and glucocorticoid use were not significantly associated with neuropathy in the adjusted model. In the overall cohort, the model including NLR demonstrated significantly improved discrimination for peripheral neuropathy compared with the base model without NLR, with the area under the ROC curve (AUC) increasing from 0.75 (95% CI: 0.69–0.81) to 0.83 (95% CI: 0.77–0.89) after including NLR (P < 0.001).
Elevated NLR is independently associated with the presence of peripheral neuropathy in RA after adjustment for major confounders, and it demonstrates incremental discriminatory value for distinguishing neuropathy status in RA.
Peripheral neuropathy is a frequent but often under-recognized extra-articular manifestation of rheumatoid arthritis (RA), frequently linked to chronic systemic inflammation. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a simple marker of systemic inflammatory burden. This study aimed to investigate the association between NLR and peripheral neuropathy in RA.
This cross-sectional study included 230 RA patients. Peripheral neuropathy was identified through clinical evaluation and nerve conduction studies. Demographic and clinical data, serological status, disease activity [28-joint Disease Activity Score (DAS28)], inflammatory markers, and complete blood counts were obtained. NLR was calculated from absolute neutrophil and lymphocyte counts. Multivariable logistic regression was used to identify factors associated with peripheral neuropathy. Discriminatory performance of NLR was evaluated using receiver operating characteristic (ROC) curve analysis.
Peripheral neuropathy was present in 93 of 230 patients (40.4%). Patients with neuropathy exhibited significantly higher NLR compared with those without neuropathy (median 3.8 vs. 2.3; P < 0.001). In multivariable logistic regression adjusting for age, disease duration, disease activity (DAS28), C-reactive protein (CRP), serological status, and glucocorticoid use, elevated NLR remained independently associated with the presence of peripheral neuropathy [adjusted odds ratio (OR) = 1.92, 95% confidence interval (CI): 1.48–2.49; P < 0.001]. Other factors significantly associated with neuropathy included older age, longer disease duration, higher DAS28, and seropositive status. CRP and glucocorticoid use were not significantly associated with neuropathy in the adjusted model. In the overall cohort, the model including NLR demonstrated significantly improved discrimination for peripheral neuropathy compared with the base model without NLR, with the area under the ROC curve (AUC) increasing from 0.75 (95% CI: 0.69–0.81) to 0.83 (95% CI: 0.77–0.89) after including NLR (P < 0.001).
Elevated NLR is independently associated with the presence of peripheral neuropathy in RA after adjustment for major confounders, and it demonstrates incremental discriminatory value for distinguishing neuropathy status in RA.
This study aimed to develop and evaluate a stacking ensemble machine learning (SEML) model that integrates deep learning (DL) algorithms to improve the accuracy of prognostic predictions for patients with head and neck squamous cell carcinoma (HNSCC).
A cohort of 215 HNSCC patients’ CT images, featuring gross tumor volume (GTV) and planning target volume (PTV) contours, was analyzed. Radiomics features were extracted and converted into quantitative data. These features were then used to train and compare a novel SEML model against standard DL algorithms to predict patient prognosis.
The proposed SEML model demonstrated superior predictive performance compared to the DL model, achieving 93% accuracy, 100% sensitivity, and 83% specificity. Statistical analysis using the chi-square test indicated no substantial difference in prediction performance between features derived from GTV and PTV contours (p > 0.05).
The SEML model effectively enhances the prognostic prediction accuracy for HNSCC based on radiomic features. This approach shows significant potential to inform clinical decision-making and support the development of customized treatment strategies for improved patient care.
This study aimed to develop and evaluate a stacking ensemble machine learning (SEML) model that integrates deep learning (DL) algorithms to improve the accuracy of prognostic predictions for patients with head and neck squamous cell carcinoma (HNSCC).
A cohort of 215 HNSCC patients’ CT images, featuring gross tumor volume (GTV) and planning target volume (PTV) contours, was analyzed. Radiomics features were extracted and converted into quantitative data. These features were then used to train and compare a novel SEML model against standard DL algorithms to predict patient prognosis.
The proposed SEML model demonstrated superior predictive performance compared to the DL model, achieving 93% accuracy, 100% sensitivity, and 83% specificity. Statistical analysis using the chi-square test indicated no substantial difference in prediction performance between features derived from GTV and PTV contours (p > 0.05).
The SEML model effectively enhances the prognostic prediction accuracy for HNSCC based on radiomic features. This approach shows significant potential to inform clinical decision-making and support the development of customized treatment strategies for improved patient care.
Edible canna is the common name given to Canna indica L., also known as Canna edulis Ker Gawl. This Andean crop has been gaining attention due to some characteristics of its rhizome starch that distinguish it from those found in other roots and tubers. Canna starch is currently used in some regions of Latin America for producing traditional baked products and desserts. In Asian countries such as China and Vietnam, it is industrially produced mainly for the elaboration of starch noodles. This review summarizes the up-to-date knowledge about edible canna as a starch source for the food industry. The composition, granule morphology, and molecular structure of canna starch are described and related to the functional properties displayed as a food ingredient. The thermal and pasting properties, gel stability, digestibility, and susceptibility to acid hydrolysis are also addressed, as well as recent reports on physical and chemical modifications to expand its applications in the food industry.
Edible canna is the common name given to Canna indica L., also known as Canna edulis Ker Gawl. This Andean crop has been gaining attention due to some characteristics of its rhizome starch that distinguish it from those found in other roots and tubers. Canna starch is currently used in some regions of Latin America for producing traditional baked products and desserts. In Asian countries such as China and Vietnam, it is industrially produced mainly for the elaboration of starch noodles. This review summarizes the up-to-date knowledge about edible canna as a starch source for the food industry. The composition, granule morphology, and molecular structure of canna starch are described and related to the functional properties displayed as a food ingredient. The thermal and pasting properties, gel stability, digestibility, and susceptibility to acid hydrolysis are also addressed, as well as recent reports on physical and chemical modifications to expand its applications in the food industry.
Human behavior depends on a collection of cognitive capacities that are expressed with complexity in humans. Although animal models have been essential for identifying fundamental neural mechanisms, many aspects of human cognition require direct investigation in the human brain. Studies of social decision-making, communication, and spatial navigation increasingly rely on intracranial electrophysiology to probe the neural basis. Related to these topics, reward processing warrants emphasis. It is not uniquely human, but it provides a central organizing signal linking motivation, learning, emotion, and choice across many human behaviors. Disruptions of reward circuits are a hallmark of numerous neurological and psychiatric conditions, giving this domain specific relevance for patient care. Fifteen studies published between 2009 and 2024 used human intracranial recordings to examine reward-related processes, nearly all in patients undergoing invasive monitoring for drug-resistant epilepsy. These studies investigated 17 neocortical and subcortical regions, most frequently the orbitofrontal cortex, using intracranial EEG, deep brain stimulation, and single-unit recordings. Recent work increasingly incorporates social interactions and computational models of learning. The purpose of this narrative review is to provide an overview of human reward processing, emphasizing how intracranial recordings have clarified the neural circuits that underlie a range of human cognitive capacities. Beyond advancing basic neuroscience, intracranial electrophysiology can inform circuit-guided interventions for neurological and psychiatric disorders.
Human behavior depends on a collection of cognitive capacities that are expressed with complexity in humans. Although animal models have been essential for identifying fundamental neural mechanisms, many aspects of human cognition require direct investigation in the human brain. Studies of social decision-making, communication, and spatial navigation increasingly rely on intracranial electrophysiology to probe the neural basis. Related to these topics, reward processing warrants emphasis. It is not uniquely human, but it provides a central organizing signal linking motivation, learning, emotion, and choice across many human behaviors. Disruptions of reward circuits are a hallmark of numerous neurological and psychiatric conditions, giving this domain specific relevance for patient care. Fifteen studies published between 2009 and 2024 used human intracranial recordings to examine reward-related processes, nearly all in patients undergoing invasive monitoring for drug-resistant epilepsy. These studies investigated 17 neocortical and subcortical regions, most frequently the orbitofrontal cortex, using intracranial EEG, deep brain stimulation, and single-unit recordings. Recent work increasingly incorporates social interactions and computational models of learning. The purpose of this narrative review is to provide an overview of human reward processing, emphasizing how intracranial recordings have clarified the neural circuits that underlie a range of human cognitive capacities. Beyond advancing basic neuroscience, intracranial electrophysiology can inform circuit-guided interventions for neurological and psychiatric disorders.
Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core NURD remodeling complex ATPase that plays a crucial role as a gene repressor. Its overexpression has been reported in several cancers. In papillary thyroid carcinomas (PTCs), CHD4 is overexpressed and associated with aggressive features of the tumor, such as proliferation, migration, and epithelial-mesenchymal transition (EMT). We previously showed in PTCs that NADPH oxidase NOX4 expression is positively regulated by BRAFV600E mutation, which is the most aggressive alteration in PTCs. In this retrospective study, we wondered whether there is a link between CHD4 and NOX4 protein expression in malignant thyroid tissues.
We explored CHD4 protein expression by immunostaining analysis in 86 human thyroid tissues: 44 thyroid tumor tissues [28 classical forms of PTCs (C-PTCs), 13 follicular variants of PTCs (F-PTCs), and three anaplastic thyroid carcinomas (ATCs)] and 42 of their normal adjacent tissues (NATs). The detection of BRAFV600E mutation was performed using Sanger sequencing and digital droplet PCR. Statistical analyses were conducted using GraphPad Prism 8 software. Various tests were used to assess the statistical relevance of different correlations, such as the chi-square test, Fisher’s exact test, and the Pearson correlation coefficient. A p-value of less than 0.05 indicates statistical significance.
The CHD4 protein expression analysis with already published data from our group (BRAFV600E status and NOX4 expression) reveals a highly significant level of CHD4 protein expression in C-PTCs compared to F-PTCs and ATC. Importantly, 70% of C-PTCs-BRAFV600E overexpress CHD4 at the protein level, confirming the positive correlation between the CHD4 expression and BRAFV600E mutation. Furthermore, a high level of CHD4 is associated with the presence of capsular breach and vascular emboli, affirming the involvement of CHD4 in thyroid tumor aggressiveness. Interestingly, we showed for the first time, to our knowledge, a positive correlation between CHD4 and NOX4 protein expression in malignant thyroid tissues.
The results of this study suggest that CHD4 could be used as a complementary molecular marker to improve the diagnosis and the management of PTCs-BRAFV600E.
Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core NURD remodeling complex ATPase that plays a crucial role as a gene repressor. Its overexpression has been reported in several cancers. In papillary thyroid carcinomas (PTCs), CHD4 is overexpressed and associated with aggressive features of the tumor, such as proliferation, migration, and epithelial-mesenchymal transition (EMT). We previously showed in PTCs that NADPH oxidase NOX4 expression is positively regulated by BRAFV600E mutation, which is the most aggressive alteration in PTCs. In this retrospective study, we wondered whether there is a link between CHD4 and NOX4 protein expression in malignant thyroid tissues.
We explored CHD4 protein expression by immunostaining analysis in 86 human thyroid tissues: 44 thyroid tumor tissues [28 classical forms of PTCs (C-PTCs), 13 follicular variants of PTCs (F-PTCs), and three anaplastic thyroid carcinomas (ATCs)] and 42 of their normal adjacent tissues (NATs). The detection of BRAFV600E mutation was performed using Sanger sequencing and digital droplet PCR. Statistical analyses were conducted using GraphPad Prism 8 software. Various tests were used to assess the statistical relevance of different correlations, such as the chi-square test, Fisher’s exact test, and the Pearson correlation coefficient. A p-value of less than 0.05 indicates statistical significance.
The CHD4 protein expression analysis with already published data from our group (BRAFV600E status and NOX4 expression) reveals a highly significant level of CHD4 protein expression in C-PTCs compared to F-PTCs and ATC. Importantly, 70% of C-PTCs-BRAFV600E overexpress CHD4 at the protein level, confirming the positive correlation between the CHD4 expression and BRAFV600E mutation. Furthermore, a high level of CHD4 is associated with the presence of capsular breach and vascular emboli, affirming the involvement of CHD4 in thyroid tumor aggressiveness. Interestingly, we showed for the first time, to our knowledge, a positive correlation between CHD4 and NOX4 protein expression in malignant thyroid tissues.
The results of this study suggest that CHD4 could be used as a complementary molecular marker to improve the diagnosis and the management of PTCs-BRAFV600E.
Acute paraplegia is a frequent and high-stake presentation in emergency departments. Spinal cord compression (SCC), particularly malignant epidural SCC, is a common oncologic emergency requiring urgent intervention, whereas Guillain-Barré syndrome (GBS) is a rarer but potentially life-threatening autoimmune polyradiculoneuropathy. Early differentiation between these conditions is essential, as delays in diagnosis and treatment are associated with irreversible neurological deficits and increased morbidity. Our objective is to synthesize recent evidence on the pathophysiology, clinical presentation, diagnosis, and management of SCC and GBS, with emphasis on early differentiation and multidisciplinary care strategies in emergency and rehabilitation settings. A scoping review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Electronic databases (PubMed, MEDLINE, Scopus, ScienceDirect, and CINAHL) were searched for English language studies published between January 2020 and June 2025. The review focused on clinical studies and reports addressing early differentiation and multidisciplinary management of SCC and GBS in emergency settings. Nineteen studies met the inclusion criteria. The review found that GBS diagnosis relies heavily on recognizing progressive symmetric weakness and preceding infectious triggers, while SCC requires immediate imaging and prompt corticosteroid administration. The limited number of studies highlights a gap in integrated emergency protocols for distinguishing these conditions. Surgical decompression remains the cornerstone of SCC management, with emerging evidence suggesting potential benefits even beyond the traditional 24-h window. This scoping review reinforces the critical need for early differentiation between SCC and GBS. Although the available literature is limited, it underscores the importance of coordinated multidisciplinary care. Clinicians must remain attentive to evolving diagnostic algorithms, particularly in light of new evidence supporting extended surgical windows for SCC.
Acute paraplegia is a frequent and high-stake presentation in emergency departments. Spinal cord compression (SCC), particularly malignant epidural SCC, is a common oncologic emergency requiring urgent intervention, whereas Guillain-Barré syndrome (GBS) is a rarer but potentially life-threatening autoimmune polyradiculoneuropathy. Early differentiation between these conditions is essential, as delays in diagnosis and treatment are associated with irreversible neurological deficits and increased morbidity. Our objective is to synthesize recent evidence on the pathophysiology, clinical presentation, diagnosis, and management of SCC and GBS, with emphasis on early differentiation and multidisciplinary care strategies in emergency and rehabilitation settings. A scoping review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Electronic databases (PubMed, MEDLINE, Scopus, ScienceDirect, and CINAHL) were searched for English language studies published between January 2020 and June 2025. The review focused on clinical studies and reports addressing early differentiation and multidisciplinary management of SCC and GBS in emergency settings. Nineteen studies met the inclusion criteria. The review found that GBS diagnosis relies heavily on recognizing progressive symmetric weakness and preceding infectious triggers, while SCC requires immediate imaging and prompt corticosteroid administration. The limited number of studies highlights a gap in integrated emergency protocols for distinguishing these conditions. Surgical decompression remains the cornerstone of SCC management, with emerging evidence suggesting potential benefits even beyond the traditional 24-h window. This scoping review reinforces the critical need for early differentiation between SCC and GBS. Although the available literature is limited, it underscores the importance of coordinated multidisciplinary care. Clinicians must remain attentive to evolving diagnostic algorithms, particularly in light of new evidence supporting extended surgical windows for SCC.
Electrochemical sensors have emerged as powerful tools for the detection and monitoring of neurotransmitters, offering high sensitivity, selectivity, and potential for real-time analysis. Neurotransmitters play a crucial role in regulating various physiological and neurological processes, and imbalances in their levels are linked to a wide range of neurological disorders, including Parkinson’s disease, depression, Alzheimer’s disease, and epilepsy. This review highlights recent advancements in electrochemical sensor technologies for neurotransmitter detection, focusing on innovations that enhance performance through the use of nanomaterials, wearable devices, and multiplexed sensing techniques. The integration of nanomaterials such as graphene, carbon nanotubes, and metal nanoparticles has significantly improved sensor sensitivity and selectivity, enabling more accurate detection even at low concentrations. Furthermore, the development of flexible, wearable, and implantable sensors is facilitating continuous, non-invasive monitoring of neurotransmitter levels in real time. Advances in multiplexed sensors are enabling the simultaneous detection of multiple neurotransmitters, providing a more comprehensive approach to disease diagnosis and management. Despite these promising developments, challenges remain, including issues of selectivity, stability, and long-term monitoring. Nevertheless, electrochemical sensors hold great potential for transforming the way neurological disorders are diagnosed and managed, offering opportunities for personalized, real-time monitoring and more effective treatment strategies.
Electrochemical sensors have emerged as powerful tools for the detection and monitoring of neurotransmitters, offering high sensitivity, selectivity, and potential for real-time analysis. Neurotransmitters play a crucial role in regulating various physiological and neurological processes, and imbalances in their levels are linked to a wide range of neurological disorders, including Parkinson’s disease, depression, Alzheimer’s disease, and epilepsy. This review highlights recent advancements in electrochemical sensor technologies for neurotransmitter detection, focusing on innovations that enhance performance through the use of nanomaterials, wearable devices, and multiplexed sensing techniques. The integration of nanomaterials such as graphene, carbon nanotubes, and metal nanoparticles has significantly improved sensor sensitivity and selectivity, enabling more accurate detection even at low concentrations. Furthermore, the development of flexible, wearable, and implantable sensors is facilitating continuous, non-invasive monitoring of neurotransmitter levels in real time. Advances in multiplexed sensors are enabling the simultaneous detection of multiple neurotransmitters, providing a more comprehensive approach to disease diagnosis and management. Despite these promising developments, challenges remain, including issues of selectivity, stability, and long-term monitoring. Nevertheless, electrochemical sensors hold great potential for transforming the way neurological disorders are diagnosed and managed, offering opportunities for personalized, real-time monitoring and more effective treatment strategies.
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