Search Results (399)

Autoimmune flares are often accompanied by abrupt surges of circulating plasmablasts—short-lived, high-output antibody-secreting cells generated through extrafollicular B-cell activation in response to microbial cues. Three categories of microbial input appear to repeatedly trigger these “plasmablast storms”: latent herpesvirus reactivations (Epstein–Barr virus, cytomegalovirus, human herpesvirus-6, varicella–zoster virus), acute respiratory or gastrointestinal infections including SARS-CoV-2, and chronic oral or gut dysbiosis. Although biologically distinct, these stimuli converge on innate sensing pathways driven by pathogen-associated molecular patterns such as unmethylated CpG DNA, single-stranded RNA, lipopolysaccharide, and bacterial lipoglycans. Through Toll-like receptors and type I interferon signalling, microbial signatures accelerate class switching, amplify inflammatory cytokine milieus, and lower B-cell activation thresholds, enabling rapid plasmablast mobilisation. Dysbiosis further maintains B cells in a hyper-responsive state by disrupting mucosal homeostasis and altering microbial metabolite profiles, thereby reducing the stimulus required to trigger plasmablast bursts. Once generated, these waves of oligoclonal plasmablasts home to inflamed tissues, where chemokine and adhesion landscapes shape their retention during flares. Emerging evidence suggests that such episodic plasmablast expansions promote autoantibody diversification, somatic hypermutation, and epitope spreading, progressively eroding tolerance. This review synthesizes these insights into a unified model in which infections and dysbiosis promote microbe-licensed plasmablast storms that influence the tempo and severity of autoimmune disease. Full article

Background/Objectives: The increasing rate of complex patients with multiple chronic somatic and/or mental disorders in modern medicine is challenging, necessitating special management programs. The aim of the present study was to identify clinical variables and the use of health services associated with the primary-physician-driven inclusion of complex patients in the “Team Management for Complex Patients” (TMCP) special program. Methods: Using validated electronic medical records of a nationwide health maintenance organization, a case–control study was performed. The study compared parameters before enrollment of complex patients included in the TMCP program with those of complex patients during the same time period who were not included, and were matched using a propensity score for age, sex, socioeconomic status, place of residence, ethnicity, smoking status, physical activity, and the balance before the day of enrollment for the major body measurements and laboratory results. Results: The control group was well-balanced, except for the South region and no physical activity. Several respiratory, cardiac, gastrointestinal, neurological, inflammatory and autoimmune diseases were significantly more common among patients included in the TMCP program than among those not included. Complex patients included in the program presented significantly higher previous rates of attending outpatient urgent care centers, visiting hospital emergency departments, hospitalization, and medication use. Conclusions: Although limited by subjective inclusion criteria and potential confounding, the present comparative study identified clinical variables associated with the identification of complex patients for enrollment into a special managed program. These associations may inform future work to develop and validate criteria to support physician decision-making in selecting complex patients for managed programs and designing healthcare resources for patients who need them most. We currently meticulously follow the outcomes of the patients included in the special managed program. Full article

The gastrointestinal (GI) tract contributes significantly to the pathogenesis of acute respiratory distress syndrome (ARDS) by influencing systemic inflammation and sepsis, which are key factors in the development of multiple organ dysfunction syndrome (MODS), while the significant impact of gut microbiota in critically ill patients, including those with sepsis and ARDS, further underscores its importance. The intestinal microbiota is vital to immune system function, responsible for triggering around 80% of immune responses. Therefore, it may be hypothesized that modifying fecal microbiota, such as through fecal microbiota transplantation (FMT), could serve as a valuable therapeutic approach for managing inflammatory diseases like lung injury (LI)/ARDS. Indeed, emerging experimental research suggests that FMT may have beneficial effects in ARDS models by improving inflammation, oxidative stress, LI, and oxygenation. However, well-designed randomized clinical trials in patients with ARDS are still lacking. Our study seeks to examine how therapeutic interventions such as FMT might benefit LI/ARDS patients by exploring the interactions between the gut and lungs in this context. Full article

High-intensity interval training (HIIT) has gained attention for its potential to improve health outcomes across various conditions. Thus, the aim of the study was to summarize studies on HIIT to understand its effects on various health outcomes. We conducted an umbrella review of systematic reviews and meta-analyses. PubMed, Cochrane Database of Systematic Reviews, EMBASE, Scopus, CINAHL, and Web of Science were searched for relevant articles. The experimental group was subjected to HIIT with or without treatment, while the control group comprised individuals who underwent alternative forms of training or were non-exercisers. Included studies were systematically analyzed for effects of HIIT and cardiovascular, respiratory, metabolic, neurological, gastrointestinal, immunological, and survival-related outcomes. Of 336 identified systematic reviews, 133 were included in the final analysis. HIIT was found to confer significant physiological benefits, including improvements in body composition, cardiovascular and metabolic parameters, and mental health outcomes. Studies demonstrated the efficacy of HIIT across diverse patient populations, with comparable or superior effects to moderate-intensity continuous training in conditions such as diabetes, cardiovascular diseases, neurological, oncologic, and pain-related disorders. Our review highlights the potential of HIIT as a time-efficient intervention for improving health outcomes and managing chronic diseases. However, interpretation of the results should be performed cautiously due to the heterogeneity observed. High-intensity interval training shows promise as an effective strategy for managing chronic diseases among diverse patient populations. Future research should focus on refining HIIT protocols and elucidating their long-term effects and sustainability. Full article

Oral health represents a complex interplay between local microbial ecology, host immune responses, and systemic physiology. Far from being an isolated entity, the oral cavity is the entry point of the gastrointestinal and respiratory tracts and harbors up to one trillion microorganisms. While commensal species maintain ecological balance, pathogenic bacteria such as Porphyromonas gingivalis drive inflammatory conditions like gingivitis and periodontitis. Studies suggest that as chronic inflammation persists and is manifested through sustained breakdown of periodontal tissues, systemic dissemination of oral pathogens contributes to bacteremia, endothelial dysfunction, and neuroinflammation. As a result, increasing evidence has been found linking these oral pathogens and inflammatory mediators to systemic conditions including Alzheimer’s disease, cardiovascular disease, and arthritis. This narrative review synthesizes current evidence linking oral health to systemic disease while addressing practical strategies to strengthen preventive care. Evidence-based interventions are presented as accessible tools for reducing both oral and systemic inflammatory burden. Importantly, this article emphasizes the public health imperative of bridging mechanistic insights with actionable oral hygiene practices. By promoting evidence-based strategies such as scaling and root planing, dietary sugar reduction, and judicious use of antimicrobial agents, individuals may reduce their risk of chronic inflammatory and degenerative diseases. Future interdisciplinary research is needed to clarify causal mechanisms and optimize preventive frameworks integrating oral-systemic health. Full article

Novel targeted therapies have transformed spinal muscular atrophy from a condition with a predictable, severe course into a more heterogeneous disorder with a range of new clinical phenotypes and outcomes. The emergence of new phenotypes in spinal muscular atrophy is a recent development in the field. The introduction of new etiopathogenic pharmacological treatments have significantly altered the natural history of the disease, leading to previously unseen clinical presentations and outcomes. Materials and Methods: We observed a cohort of 104 patients (children and adolescents), considering the number of SMN2 gene copies, the use of respiratory ventilation support devices and gastrointestinal support, and finally, their evolution on clinical-functional scales with physical therapy and rehabilitation interventions. With the increasing availability of effective therapies for spinal muscular atrophy, outcome measurement in clinical practice and research requires highly sensitive and reliable tools. In this study, motor function was systematically evaluated using two validated scales—the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Functional Motor Scale Expanded (HFMSE)—which are specifically designed to capture incremental changes in motor skills across the spectrum of SMA severity and age groups. Results: The median scores on the validated tools steadily increased over the 24 months of follow-up. Starting from 29 at baseline, the scores rose to 36 at 6 months, then to 39 at 12 months, 43 at 18 months, and 44.5 at 24 months. The Friedman test showed that these changes were statistically significant (p < 0.01). Moreover, each follow-up score was significantly higher than both the baseline and the previous time point (all p < 0.01), showing continuous improvement over time. Conclusions: These findings reveal that the development of new SMA phenotypes is closely linked to the stage of disease at which treatment is initiated. Earlier intervention consistently enables patients to acquire previously unattainable motor skills. Consequently, enhancing diagnostic precision and expediting therapy initiation is crucial for maximizing clinical benefits and facilitating optimal functional outcomes. Full article

Centella asiatica, a widely used medicinal herb in Oriental and increasingly Western medicine, is applied for wound healing, dermatological disorders, and gastrointestinal illness. We investigated the effects of fermented C. asiatica extract (FCAE), prepared with Lactobacillus, on airway inflammation in a murine model of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke extract (CSE) and lipopolysaccharide (LPS). CSE/LPS stimulation caused marked immune cell infiltration in airways. FCAE (100 and 200 mg/kg) reduced neutrophils in the bronchoalveolar lavage fluid (BALF) by 26.03% and 70.11%, respectively, and decreased activated T cells and B cells in the lung, mediastinal lymph nodes, and Peyer’s patches, while inhibiting collagen fibrosis. FCAE significantly reduced IL-1α (32.51%), CXCL1 (47.63%), CXCL2 (45.37%), and TNF-α (39.51%) levels in the BALF compared with the control group. It also downregulated the expression of muc5ac (58.39%), CXCL1 (67.32%), CXCL2 (57.60%), and TNF-α (54.61%) and suppressed p-STAT3 activation by 50.22%. Furthermore, FCAE enhanced tracheal phenol red secretion by 229.62%, indicating expectorant activity. UPLC analysis identified nine components, which, together with FCAE, inhibited RANTES, TNF-α, and IL-6 in inflammation-induced BEAS-2B cells. Overall, FCAE attenuates immune activation and airway inflammation, supporting its potential as a candidate therapy or functional food for respiratory diseases. Full article

Human adenoviruses (HAdV) comprise more than 100 genotypes with species-specific differences in tropism and immune response and can cause severe infections in immunocompromised patients. This study aimed to characterise the HAdV species involved in pediatric infections to assess their clinical impact and guide future therapeutic strategies based on AdV-specific T-cell responses. Between January and October 2024, 595 pediatric HAdV diagnoses were made at the Bambino Gesù Children’s Hospital (Rome), and whole-genome sequencing was performed on 60 samples. Most patients (91.7%) were hospitalised, including both immunocompetent (75%) and immunocompromised (25%) children. Gastrointestinal and respiratory symptoms were more common in immunocompetent patients, whereas immunocompromised patients experienced longer hospitalisations and persistent viral infections. Species F (F41) was most prevalent (63.3%), especially among immunocompetent patients, while species C and A predominated in immunocompromised children, with species A associated with severe disease. Viral loads were significantly higher for species F than for species A and C, independent of immune status. Co-infections were frequent (63.3%), with species C particularly linked to them. In conclusion, HAdV distribution differed by immune status, with species F predominating in immunocompetent children and species C and A more common in immunocompromised patients. Whole-genome sequencing may enhance surveillance, enable earlier diagnosis, and support the development of genotype-specific immunotherapies. Full article

This review integrates the biology and clinical translation of hydrogen sulfide (H₂S) in balneology. It frames H₂S as a gasotransmitters with dual chemical and biological actions and summarizes the H₂S/HS⁻ equilibrium as a function of pH, temperature, and oxygenation, which governs bioaccessibility in sulfurous waters. Endogenous and exogenous sources, transport, and mitochondrial catabolism are outlined, together with core cellular mechanisms: protein persulfidation; activation of Nrf2/ARE; modulation of NF-κB; regulation of ion channels; and engagement of PI3K/Akt, MAPK/ERK, and Wnt pathways, plus epigenetic interactions with HDACs and sirtuins. Preclinical and clinical evidence in dermatology, musculoskeletal disease, and respiratory care is synthesized, alongside metabolic, cardiovascular, gastrointestinal, and renal effects. Technical aspects that preserve the bioactive fraction of H₂S while meeting environmental safety limits are highlighted. Routes of administration (bathing, peloids, inhalation, and drinking cures) and key operational parameters are described. Overall, the review links physicochemical and molecular foundations with clinical indications for sulfurous waters and derivatives and identifies opportunities for research and development in H₂S donors and thermal cosmetics without extrapolating beyond the available data. Full article

As breeding practices in dairy industry shift toward the use of beef semen, the number of calves sent off-site for rearing has increased. The limited literature describes mortalities by season, sex, or breed within calf ranches. The objectives were to identify primary and co-morbidities at necropsy in calf ranches and determine whether causes of death varied by season, sex, breed, or ranch. Systematic necropsies (n = 243) were performed monthly over 12 months at four ranches by technicians with diagnoses confirmed by veterinarians. Mortalities were classified as respiratory (RESP), gastrointestinal (GI), septicemia (SEPT), or other (OTH) based on gross necropsy findings. A subset from ranches with 12 months of necropsy data (n = 175) was analyzed using generalized linear and multinomial models to evaluate associations between RESP diagnoses or GI lesion locations and 4-month periods, sex, breed, and ranch. Respiratory disease was most common (67.5%), followed by GI (11.5%), SEPT (9.5%), and OTH (11.5%). Most (86.0%) lacked co-morbidities; RESP (7.0%) and OTH (3.7%) were the frequent primary diagnoses with co-morbidities. No significant associations were detected with time, sex, breed, or ranch (p ≥ 0.11 for RESP; p ≥ 0.13 for GI). Although inferences were limited by sample size, findings provide insight into calf mortalities and co-morbidities in commercial ranches. Full article

Background/Objectives: The approval of disease-modifying therapies has significantly improved outcomes for patients with spinal muscular atrophy (SMA), yet their long-term safety profiles remain under continuous evaluation. This study aimed to assess trends in the reporting of suspected adverse drug reactions (ADRs) associated with nusinersen, onasemnogene abeparvovec, and risdiplam across the European Union. Methods: We conducted a secondary analysis of annual suspected ADR data reported to EudraVigilance from 2017 to 2024 for the three approved disease-modifying therapies for SMA. On top of general reporting trend, specific adverse reactions of interest included post-lumbar puncture syndrome for nusinersen, liver toxicity and elevated serum troponin for onasemnogene abeparvovec, and respiratory and gastrointestinal reactions for risdiplam. Joinpoint regression analysis was used to evaluate annual percent changes and identify statistically significant trend segments for each medicine. Results: The reporting of suspected ADRs for nusinersen showed an initial increase, followed by a significant decline after 2019. Onasemnogene abeparvovec exhibited a continued but decelerating increase in suspected ADRs, while risdiplam demonstrated a consistent upward trend across all reported reactions. Conclusions: Diverging patterns in adverse reaction reporting suggest a stabilizing safety profile for nusinersen and potential emerging safety signals for risdiplam and onasemnogene abeparvovec, underscoring the need for ongoing continued pharmacovigilance (e.g., post-authorization studies and spontaneous reporting). Full article

Despite the health concerns regarding alcohol and its link to cancer, moderate consumption of red wine has been associated with healthy aging and longevity, defined as up to one drink per day for women and two drinks per day for men (approximately 142 mL or 5 oz per drink). Previous research has revealed the health benefits of red wine, particularly in relation to cardiovascular disease. However, the influence of genetic factors on these benefits remains to be elucidated. In this study, we explored genes linked to red wine and created a curated gene set that intersects with those related to centenarians, which are markers of exceptional longevity. By analyzing literature from over 190 databases, we identified and validated a curated list of 43 genes associated with red wine and centenarians. We conducted gene set enrichment analysis as well as enrichment analysis of diseases and their tissue distributions. The results suggest that these genes play a crucial role in stress response and apoptosis, which are essential for cell survival and renewal. Additionally, these genes were enriched in pathways associated with smooth muscle cell proliferation, neuroinflammation, nucleotide excision repair, and lipoprotein metabolism (false discovery rate, FDR < 3 × 10⁻⁷). Gene set enrichment analysis indicated significant tissue distribution in the gastrointestinal, cardiovascular, and respiratory systems. Furthermore, the disease–gene enrichment analysis pointed to associations with diseases related to tissues and organs, including cardiovascular disease (heart disease and stroke), type 2 diabetes, gastrointestinal diseases and metabolic diseases, immune diseases, and cancer (FDR < 9.37 × 10⁻⁶); notably, cardiovascular diseases, diabetes, and cancer are leading causes of death, suggesting that these genes may be protective against those diseases. Our review of the literature indicates that individuals who do not currently drink alcohol should not be encouraged to start. However, we propose that moderate consumption of red wine, especially for middle-aged to older adults after 40 years old, can provide significant health benefits due to its components and the positive effects of hormesis. Although further research is necessary to uncover additional genes, this study provides the first genetic overview of the health benefits of red wine, emphasizing its potential in supporting healthy aging and longevity. Full article

Background: Acute infections in children are prevalent and often lead to antibiotic overuse due to the lack of evidence-based alternative approaches. Phytotherapeutic, homeopathic treatments and bee products are frequently sought as alternative or adjunctive therapies. This scoping review aims to map the existing evidence on the efficacy and safety of these interventions in managing acute pediatric infections. Methods: A comprehensive literature search was conducted across multiple databases to identify studies assessing the use of phytotherapeutic, homeopathic remedies and bee products in children with acute infections. Gastrointestinal infections were not considered since the use of non-antibiotic treatments (probiotics) in these conditions has been widely addressed. Effectiveness: Phytotherapeutic agents and bee products demonstrated promising results in reducing symptom severity and duration in respiratory infections, whereas homeopathic data were limited and inconsistent. Regarding safety, both interventions were generally well-tolerated, with few adverse events reported. No studies or very limited evidence were available for other acute infections such as urinary, dermatological, osteoarticular and nervous system infections. Conclusions: Phytotherapeutic interventions and bee products, particularly in acute upper respiratory tract and acute bronchitis, show encouraging signals of efficacy and safety in pediatric populations. However, evidence for their use in other frequent childhood infections, such as otitis media, or gastrointestinal infections, is almost entirely lacking. In addition, the available literature on homeopathic remedies is scarce and methodologically inconsistent, preventing any firm conclusions. Well-designed, large-scale clinical trials focusing on these underexplored conditions are needed to clarify the potential role of phytotherapeutics and homeopathy in pediatric infectious diseases. Full article

Colonoscopy is the gold standard for colorectal cancer screening and diagnosis of gastrointestinal disorders, yet the procedure can still provoke anxiety and pain in many patients. Advances in anesthesia and sedation techniques have significantly improved patient tolerance while maintaining procedural efficiency and safety. This review explores the physiological mechanisms of pain during colonoscopy, compares anesthetic and sedative agents—including newer drugs like remimazolam and dexmedetomidine—and evaluates emerging evidence from recent studies on sedation efficacy, safety, and patient outcomes. Special attention is given to high-risk patient populations, including those with obesity, obstructive sleep apnea, cardiovascular diseases, respiratory disorders and frailty syndrome. Propofol-based sedation remains the most commonly used agent for deep sedation. However, newer pharmacological agents with enhanced pharmacokinetic properties and improved safety profiles are increasingly influencing contemporary anesthesia practices. An individualized approach to sedation is essential. Incorporating current evidence into clinical decision-making optimizes both patient experience and procedural outcomes. Full article

Environmental pollution with microplastics (MPs) and nanoplastics (NPs) continues to increase. These pollutants have been found in the environment (water, soil, and air) as well as in human tissues and biological fluids. Oral, inhalation, and dermal pathways play key roles in human exposure to plastic particles. The primary sources of exposure are foods, beverages, air, and dust. Polymers can penetrate the skin primarily via endocytosis, exocytosis, passages through cell-to-cell junctions, and interaction with the extracellular matrix. However, the health effects of dermal exposure remain poorly understood. Microplastics and NPs have been detected in the gastrointestinal, respiratory, circulatory, urinary, reproductive, and nervous systems, causing detrimental effects in each. Such effects include oxidative stress, inflammation, cellular damage, and protein aggregation. Furthermore, their presence has been linked to cardiovascular and neurodegenerative diseases. However, standardized protocols for analyzing NPs and MPs in human organs and tissues have not yet been established or legally regulated. Further research is needed to fully determine exposure thresholds, but legislative and lifestyle changes can already be implemented. Full article