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Pulmonary tuberculosis (TB) remains a global health threat, with individual genetic determinants like Toll-like receptor 2 (TLR2) gene variations potentially modulating immune responses to Mycobacterium tuberculosis. This systematic review evaluates the role of TLR2 polymorphisms in influencing susceptibility to and clinical manifestations of pulmonary TB. Following PRISMA guidelines, a comprehensive search of PubMed, Scopus, and ScienceDirect was conducted through July 2024 for observational studies investigating TLR2 single-nucleotide polymorphisms (SNPs) and active TB. Risk of bias was assessed using the Newcastle-Ottawa Scale. Of 8878 identified articles, 32 studies met the inclusion criteria. The most frequently investigated variants, Arg753Gln (rs5743708), -196 to -174 del, and rs3804099, were consistently associated with increased TB susceptibility, particularly in Asian and African populations. Furthermore, specific polymorphisms correlated with greater disease severity, including cavitary lesions and aggressive clinical progression. In conclusion, TLR2 genetic polymorphisms significantly increase the risk of developing pulmonary TB and contribute to more severe clinical outcomes. These findings emphasize the potential of genetic profiling in enhancing TB control strategies and developing personalized diagnostic or therapeutic approaches.

Objective: This review is to systematically evaluate the clinical effectiveness and safety of acupuncture therapy for patients with post-stroke neurogenic bladder (PSNB). Methods: We included randomized controlled trials (RCTs) evaluating any type of acupuncture treatment for PSNB. Data extraction and quality assessment using Cochrane Risk of Bias 2.0 were performed. Meta-analysis was conducted for total effective rate (TER) and urodynamic parameters. Results: Ten RCTs involving 727 participants were included. Meta-analysis showed that acupuncture was associated with a reduction in residual urine volume (RUV), and increases in maximum cystometric capacity (MCC), and maximal urinary flow rate (Qmax). Acupuncture also showed a higher TER compared to control groups (RR = 1.23, 95% CI [1.15, 1.33], p < 0.001). However, wide 95% prediction intervals for urodynamic parameters indicated substantial uncertainty for future clinical applications. Adverse events were mild and infrequent, but only partly reported in two studies among included trials. Conclusions: Acupuncture as an adjunctive therapy suggests potential trends for improving clinical efficacy and urodynamic parameters in PSNB patients. However, no definitive conclusions can be drawn regarding its clinical efficacy or safety due to the very low certainty of evidence, high methodological heterogeneity, and limited reporting of adverse events. Therefore, these results must be interpreted with extreme caution. Further high-quality, large-scale randomized controlled trials with standardized protocols are essential to establish robust evidence regarding its clinical effectiveness and safety. Protocol registration: PROSPERO CRD42025643092.

Background and Objectives: Rituximab, a monoclonal antibody targeting CD20+ B-cells, is used in autoimmune diseases and B-cell malignancies. Recently, rituximab has been used as an induction agent in kidney transplantation. Our study evaluates the efficacy of rituximab induction on biopsy-proven acute rejection (BPAR), patient survival, and graft survival in ABO-compatible patients. Materials and Methods: A systematic literature search was performed across five databases, following PRISMA guidelines, and the protocol was registered in PROSPERO (CRD42024603984). The inclusion criteria consisted of randomized controlled trials (RCTs), exploring the impact of rituximab induction on eligible kidney transplant recipients with BPAR, graft, and patient survival as the primary outcomes. Risk ratios (RR) with 95% confidence intervals (CI) were estimated by the random-effects model. The risk of bias was assessed via the Cochrane ROB-2 tool across five domains. Results: From an initial 859 potentially relevant studies, three RCTs, including 454 patients, met the inclusion criteria. At 6 months, rituximab was associated with a non-significant reduction in the risk of BPAR (RR 0.76; 95% CI, 0.50-1.15; I2 = 0%). Similarly, patient survival remained unchanged at 6 months (RR 1.01; 95% CI, 0.98-1.04; I2 = 0%). Due to significant heterogeneity, long-term outcomes were assessed using narrative synthesis, which revealed no additional benefit for rituximab in terms of graft or patient survival. Furthermore, potential safety concerns-especially in terms of infection risk-were noted. The certainty of this evidence was low, due to clinical heterogeneity in the included studies causing very serious indirectness. Conclusions: Induction with rituximab provides no significant benefit over standard regimens. Thus, its routine use in ABO-compatible renal transplants may not be justified. The available evidence is of low certainty. Further trials are needed before drawing a firm conclusion and to determine the best dosage, timing, and combinations.

BACKGROUND: Postprandial triglyceride (TG) metabolism represents a dynamic dimension of lipid physiology that complements conventional fasting lipid assessment. Although low-density lipoprotein cholesterol (LDL-C) remains the primary therapeutic target in cardiovascular prevention, residual cardiovascular risk persists in many individuals despite apparently adequate fasting lipid control. Because most individuals spend the majority of their waking hours in a fed state, postprandial TG responses may provide clinically relevant insight into metabolic flexibility, dietary exposure, and the efficiency of TG-rich lipoprotein clearance. METHODS: This narrative review was conducted using a literature search guided by predefined themes, keywords, and databases, without following a formal systematic review protocol. Randomized controlled trials, observational studies, meta-analyses, and major reviews addressing postprandial lipid metabolism, dietary determinants, and cardiometabolic risk were included, with priority given to human studies. RESULTS: Postprandial TG responses are strongly influenced by dietary composition, eating patterns, and metabolic health. Individuals with insulin resistance, type 2 diabetes, obesity, and metabolic-associated steatotic liver disease (MASLD) frequently demonstrate exaggerated or prolonged postprandial lipemia even when fasting TG concentrations appear acceptable. While circulating TGs serve as practical clinical markers of postprandial lipid handling, cholesterol-enriched remnant lipoproteins more closely reflect atherogenic burden. Nutritional interventions, weight management, and physical activity consistently improve postprandial TG dynamics, whereas pharmacologic therapy provides additional benefit in selected high-risk patients. Non-fasting TG measurements may provide additional insight into postprandial lipid metabolism and residual cardiovascular risk, although standardized protocols and validated clinical thresholds remain to be established. CONCLUSIONS: Postprandial TG metabolism provides clinically meaningful information beyond fasting lipid measurements and represents a useful adjunct for refining residual cardiovascular ris

Background: Ecuador is a genetically diverse population setting shaped by long-term interactions among Native American, European, and African populations across distinct ecological regions. Although multiple studies have examined ancestry patterns in Ecuadorian populations, the available evidence remains fragmented and methodologically heterogeneous. Objective: To systematically identify, critically appraise, and synthesize published studies on genetic ancestry and population structure in Ecuador. Methods: A systematic review was conducted in accordance with PRISMA 2020. Searches were performed in PubMed/MEDLINE, Scopus, Web of Science Core Collection, SciELO, and Google Scholar through 31 January 2026. Eligible studies reported extractable ancestry-related data from Ecuadorian populations using autosomal, mitochondrial DNA, Y-chromosomal, or other ancestry-relevant genetic markers. Methodological quality was assessed using an adapted Joanna Briggs Institute framework. Owing to substantial heterogeneity across marker systems, sampling strategies, and ancestry inference methods, findings were synthesized qualitatively rather than by meta-analysis. Results: Of 1243 records identified, 12 studies met the inclusion criteria. Across marker systems, the evidence consistently supported a three-way admixture framework involving Native American, European, and African ancestry components, together with substantial regional and population-specific heterogeneity. Autosomal studies generally showed higher Native American ancestry in Highland and Native American populations, whereas African ancestry was more prominent in Afro-Ecuadorian and some Coastal populations. Uniparental markers further supported persistent sex-biased admixture, with predominant Native American maternal lineages and comparatively greater European or African paternal contributions depending on region and population history. Conclusions: Ecuadorian populations share a broad three-way admixture framework, but with marked internal heterogeneity across regions and population groups. These findings highlight the importance of geographic and demographic context in ancestry interpretation and the need for larg

Life expectancy (LE) varies widely across Organization of Islamic Cooperation (OIC) countries, reflecting differences in economic, social, environmental, and health-system conditions. This review aimed to synthesize quantitative evidence on determinants of LE at birth in OIC member countries. The study was conducted in accordance with the PRISMA guidelines, and a systematic search of electronic databases was performed up to September 2025. After screening 5312 records and assessing full texts, studies were appraised using the Joanna Briggs Institute checklists, with an inclusion threshold of ≥80%. A total of 54 studies, mainly ecological, time-series, and panel analyses using national-level data, were included. Higher gross domestic product per capita, education, employment, and health expenditure were consistently associated with longer LE. In contrast, poverty, income inequality, air pollution, and carbon dioxide emissions were associated with shorter LE. Clear differences were observed across World Bank income groups, with LE being lowest in low-income OIC countries and highest in high-income Gulf Cooperation Council states, where gains were driven more by health-system resources than by income growth. Improving LE in OIC countries requires integrated economic, social, environmental, and health-system policies.

OBJECTIVE: This review aimed to synthesize evidence on the design characteristics, implementation considerations, and operational challenges of mobile cancer screening units. METHODS: A PRISMA-guided review was conducted. Data extracted included screening type, target population, program characteristics, mobile unit features, and reported implementation barriers. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Sixty-four articles published across 13 countries met the inclusion criteria. Most interventions focused on breast cancer screening (n = 37), followed by lung (n = 11), cervical (n = 6), colorectal, skin, prostate, and multi-cancer screening programs. MSUs were most frequently deployed in urban areas (21 urban/18 rural/17 both). Several comparative studies (fixed programs vs. MSUs) reported higher screening uptake in mobile programs, although findings varied substantially by setting, population, and study design. However, adherence and clinical outcomes varied, often reflecting baseline socioeconomic differences in the populations served. Common implementation barriers included follow-up coordination challenges, program costs, equipment and space limitations, and gaps in referral and reimbursement systems. CONCLUSIONS: These findings highlight the potential of mobile screening units as public health strategies to expand access to cancer screening while underscoring the need for stronger implementation frameworks and long-term evaluation of program outcomes.

Antibiotic-associated diarrhea (AAD) is primarily driven by disruption of the gut microbiota accompanied by intestinal mucosal injury. Although multiherb formulations are widely used in East Asian medicine, their collective ecological effects and integrated microbiome-host mechanisms have not been systematically synthesized. This systematic review included 17 preclinical studies that investigated multiherbal formulations in AAD models. Given the substantial heterogeneity in the formulation composition, experimental design, and analytical platforms, a descriptive synthesis was performed. The included formulations were categorized into four clusters based on their shared herbal composition: Qiwei Baizhu San (QWBZP), Lizhong Tang (LZT), Gegen Qinlian Tang (GQT), and other supportive multiherbal formulations. The cluster-based synthesis revealed distinct convergent therapeutic strategies. The QWBZP and LZT clusters primarily supported the restoration of host metabolic and digestive functions, whereas the GQT cluster exhibited potent pathogen control effects with the suppression of opportunistic taxa. Across all clusters, a convergent microbiome-host response emerged, characterized by enrichment of commensal bacteria (e.g., Lactobacillus), upregulation of tight junction proteins (e.g., ZO-1, occludin), and attenuation of pro-inflammatory mediators (e.g., TNF-α, myeloperoxidase). Multiherb formulations in AAD models not only act as microbial modulators but also function as host-directed modulators that stabilize the intestinal homeostatic niche. Botanical interventions may facilitate endogenous microbiome recovery by reinforcing mucosal integrity and reducing environmental resistance. This ecological framework provides a rationale for future translational studies evaluating integrated herbal-probiotic strategies and precise microbiome management for patients with AAD, while further clinical validation is warranted.

The disproportionately severe disease course of diabetic patients with SARS-CoV-2 infection was repeatedly observed by clinicians during the COVID-19 pandemic. The overlap between metabolic impairment, viral pathophysiology, and chronic inflammation created a pattern that urged deeper examination. The aim of this paper was to review and synthesize evidence regarding the interaction between diabetes mellitus and COVID-19. We synthesized evidence across mechanistic pathways (immune dysregulation, chronic inflammation, ACE2/DPP-4-related signaling, endothelial dysfunction, and pancreatic involvement) and key clinical outcomes (severity, intensive care unit (ICU) admission, mortality, dysglycaemia/new-onset diabetes, and DKA). This systematic search was conducted in PubMed, Clinical Key, and Google Scholar. The eligibility criteria included papers on adults (≥18 years) with pre-existing diabetes mellitus (type 1 or type 2) or newly diagnosed diabetes/hyperglycemia and confirmed SARS-CoV-2 infection, published between January 2020 and October 2025, in English language. The PRISMA guidelines were used for data extraction. We identified 412 articles, out of which only 30 met all the inclusion criteria. Diabetes was consistently evoked as a major risk factor for severe COVID-19, being associated with higher susceptibility to pneumonia, respiratory failure, ICU admission, and mortality. The explanation lies in the impaired immune system, endothelial dysfunction, and metabolic repercussions imposed by hyperglycemia. Several antidiabetic drugs appeared protective in multiple cohorts. In conclusion, the accumulated evidence underscores the tight interplay between metabolic disease and COVID-19. Essentially, the clinical management of these patients would be a thoughtful selection of antidiabetic therapy and close metabolic monitoring.

Acute coronary syndrome patients undergoing percutaneous coronary intervention remain at high risk for major adverse cardiovascular events (MACE: cardiovascular mortality, non-fatal myocardial infarction, and stroke). Inflammatory-oxidative stress biomarkers are potential prognostic tools; however, the influence of sampling timing-pre-procedural versus post-procedural-remains unclear. This meta-analysis evaluated six biomarkers: sST2, GDF-15, OPG, sLOX-1, H-FABP, and Galectin-3. Pooled Hazard Ratios (HRs) for time-to-event outcomes and Standardized Mean Differences (SMDs) between event and non-event groups were synthesized using random-effects models involving 40 studies (18,933 patients). Elevated pre-procedural levels of sST2 (HR = 3.32, p < 0.0001), GDF-15 (HR = 3.00, p < 0.0001), sLOX-1 (HR = 2.61, p = 0.0023), and OPG (HR = 1.79, p = 0.0206) significantly predicted MACE. Notably, pre-PCI sST2 strongly predicted heart failure hospitalization (HR = 6.30, p < 0.0001). Additionally, pre-PCI H-FABP demonstrated a moderate significant effect on adverse outcomes (SMD = 0.67, p < 0.0001). While pre-PCI Galectin-3 was not significant, its post-procedural levels showed a large significant effect (SMD = 1.15, p < 0.0001). In conclusion, inflammatory and oxidative stress biomarkers, particularly sST2 and GDF-15, demonstrate consistent associations with adverse outcomes in ACS patients undergoing PCI, offering more reliable baseline risk stratification than post-procedural measurements.

BACKGROUND: Low-volume high-intensity interval training (LVHIIT) is known to improve cardiometabolic health; however, the potential additive effects of combining LVHIIT with inspiratory muscle training (IMT) in reducing the severity of metabolic syndrome (MetS) have not been fully explored. This study aimed to evaluate the effects of 8 weeks of IMT combined with LVHIIT on cardiorespiratory fitness, MetS parameters, and respiratory muscle function in individuals with MetS. METHODS: This randomized, controlled, double-blind trial included 38 adults with MetS, aged 42 to 60 years, who were randomly assigned to 3 groups: LVHIIT (n = 12), LVHIIT + IMT (n = 14), and control (n = 12). The primary outcome was the change in maximal oxygen consumption (VO2max) after 8 weeks. Secondary outcomes included MetS z-score, anthropometric measures, metabolic blood markers, and respiratory muscle strength and endurance. All outcomes were assessed at baseline and after the 8-week intervention. RESULTS: The mean age of participants was 50 ± 5 years, and 67% were women. Significant group × time interactions were observed for VO2max, oxygen uptake efficiency slope, heart rate recovery at 1 minute, waist circumference, hip circumference, visceral fat ratio, fasting plasma glucose, glycosylated hemoglobin A1c, and MetS z-score (P < .05). Both LVHIIT and LVHIIT + IMT groups showed significant improvements in VO2max (P < .001). Respiratory muscle strength and endurance increased significantly only in the LVHIIT + IMT group (P < .001). CONCLUSION: Eight weeks of LVHIIT combined with IMT led to improvements in cardiorespiratory fitness, respiratory muscle function, and key MetS components, including MetS z-score. Integrating IMT into LVHIIT may be an effective, clinically feasible, and time-efficient approach to improve cardiometabolic health in individuals with MetS in cardiac rehabilitation.

The randomized, multicenter, prospective Phase 3 trial (NCT02777736) evaluated central nervous system (CNS) prophylaxis using either intravenous (i.v.) or intrathecal (i.t.) methotrexate (MTX) in diffuse large B-cell lymphoma (DLBCL). Treatment consisted of six cycles of R-CHOP + 2xR or DA-EPOCH-R + 2xR. Patients with intermediate or high-risk CNS International Prognostic Index (CNS-IPI) were randomized to receive CNS prophylaxis with either 2 doses of MTX 3 g/m2 i.v. (arm A) or 6 doses of MTX 12 mg i.t. (arm B). Patients with low-risk CNS-IPI did not receive MTX prophylaxis (arm C). The primary objective was to compare the cumulative incidence of CNS relapse between arms A and B. Secondary objectives included evaluation of overall response rate (ORR), complete remission rate (CRR), progression-free survival (PFS), overall survival (OS), and treatment-related safety across all arms. Between 7/2015 and 5/2024, a total of 100 patients were enrolled: 30 in arm A, 31 in arm B, and 39 in arm C. ORR did not differ among arms (p = 0.20). During a median follow-up of 54.9 months, CNS relapses were observed in three patients who had received MTX prophylaxis-one in arm A and two in arm B. The 5-year cumulative incidence of CNS relapse was 0% in arm A and 8.7% in arm B (p = 0.72). However, due to the small sample size, the primary endpoint results are inconclusive. Median PFS was comparable between arms A and B (HR 0.66, p = 0.20). MTX i.v. was associated with a significantly higher grade ≥ 3 neutropenia (p = 0.0003) and infection (p = 0.0063). The higher infection rate contributed to a worse 5-year OS in arm A versus B (47.2% vs. 72.4%, HR 0.46, p = 0.04). Conclusion: our trial faced limitations due to a low number of randomized participants, making the interpretation of results challenging. A larger, international randomized trial is necessary to determine the benefit of CNS prophylaxis. © 2026 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.

AIMS: The aim of this study was to compare clinical, performance-based, and patient-reported outcomes between patients with moderate-to-severe hip osteoarthritis (OA) who were treated with total hip arthroplasty (THA) or conservative treatment with a self-directed exercise programme. METHODS: We conducted a single-centre, randomized controlled trial including 120 participants with radiologically confirmed moderate-to-severe hip OA (Kellgren-Lawrence grades 2 to 4). Participants were randomly allocated (1:1) to receive either THA combined with postoperative rehabilitation or a self-directed exercise programme. The primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Harris Hip Score (HHS) at 12 months. Minimal clinically important differences (MCIDs) were predefined as 11 points for WOMAC and 15.9 points for HHS. Secondary outcomes included WOMAC at six months, as well as WOMAC subscales, health-related quality of life (HRQoL) RAND 36-Item Health Survey 1.0 (RAND-36) domains, and physical performance tests (chair stand, 40 m walk, and stair climb). RESULTS: At 12 months, the THA group demonstrated significantly greater improvements than the conservative group in WOMAC total score (-30.9 (95% CI -34.9 to -27.0) vs -3.7 (95% CI -8.2 to 0.9; between-group difference -27.1 points (95% CI -32.4 to -21.8)) and HHS (29.8 (95% CI 25.8 to 33.9) vs 5.7 (95% CI 2.4 to 9.0); difference 24.1 (95% CI 19.6 to 28.7)), both exceeding MCID thresholds. Overall, 23 participants (38%) in the conservative group underwent THA during the study; two participants in the THA group declined surgery. The THA group also showed superior gains across all performance-based tests and most RAND-36 domains. CONCLUSION: In patients with moderate-to-severe hip OA, THA combined with postoperative rehabilitation provides clinically meaningful improvements in pain, function, and HRQoL compared with a self-directed exercise programme alone. These findings reinforce THA as the preferred option for eligible patients. © 2026 The British Editorial Society of Bone & Joint Surgery.

BACKGROUND: Metabolic bariatric surgery (MBS) effectively reduces fat mass (FM), but how to best preserve muscle and bone mass after MBS is unknown. OBJECTIVE: This study aimed to evaluate the effect of aerobic, resistance and combined exercise regimens on body composition, bone mineral density (BMD) and physical function in adults following MBS. METHODS: Patients were randomized into aerobic, resistance, combined and control groups after undergoing MBS. Exercise groups completed a 26-week supervised program (three sessions per week) with progressively increasing intensity. The primary outcome was the change in fat-free mass (FFM) measured by dual-energy X-ray absorptiometry (DXA). Secondary outcomes included FM, hip, femoral neck and lumbar spine BMD, serum collagen type I C-telopeptide (CTX) and physical function (e.g., 6-min walk test and handgrip strength). Between-group differences were assessed using Bayesian analysis of covariance (ANCOVA) adjusted for age, sex, surgery type and baseline body mass index, with credible differences inferred when the 95% credible interval of the standardized effect size excluded zero. Associations between outcomes were assessed using Pearson correlation. RESULTS: Of 443 eligible candidates, 58 participants (aged 18-65 years, 70% women, BMI 41.7 ± 4.4 kg/m2) were randomized to aerobic (n = 15), resistance (n = 13), combined (n = 14) or control (n = 16) groups, and 91.3% were included in the analysis. The combined exercise group preserved more FFM (-5.1 ± 2.8 kg vs. -7.7 ± 2.8 kg; ES 0.60 [0.41, 0.77]) and reduced more FM (-11.9% ± 5.7% vs. -10.1% ± 4.9%, ES -0.64 [-0.85, -0.40]) than control. Aerobic training most attenuated total hip BMD loss (-0.037 ± 0.033 g/cm2, -3.3%) compared with control (-0.058 ± 0.021 g/cm2, -5.4%; ES 0.69 [0.42, 0.92]) and modestly attenuated femoral neck BMD loss (ES 0.30 [0.11, 0.48]), with no differences at the lumbar spine. The relative increase in serum CTX was smaller in the aerobic (157.8%; ES -0.44 [-0.65, -0.18]) and combined groups (161.8%; ES -0.42 [-0.63, -0.17]) compared with control (196.4%). Physical function improved modestly, with aerobic training showing a greater improvement in wa

BACKGROUND: Mim8 (denecimig), a bispecific antibody mimicking activated factor VIII, was developed for bleeding prophylaxis in patients with hemophilia A with or without factor VIII inhibitors. METHODS: In this phase 3, randomized trial, we assigned patients 12 years of age or older with hemophilia A with or without inhibitors to receive subcutaneous Mim8 once weekly or once monthly at a dose tiered according to body weight and given in a fixed injection volume (0.8 ml). Patients who had been receiving on-demand treatment before the trial were assigned in a 1:1:1 ratio to continue on-demand treatment (group 1) or receive Mim8 once weekly (group 2a) or once monthly (group 2b). Patients who had been receiving clotting factor concentrates during a run-in phase were assigned in a 1:1 ratio to receive Mim8 once weekly (group 3) or once monthly (group 4). The first primary end point was the annualized rate of treated bleeding events (those treated with a coagulation factor product) in an evaluation of Mim8 in group 2a and Mim8 in group 2b as compared with on-demand treatment in group 1. The second was the annualized rate of treated bleeding events in an intrapatient evaluation of Mim8 in group 3 and Mim8 in group 4 as compared with clotting factor concentrate prophylaxis during the run-in phase. RESULTS: Of the 58 patients in the pretrial on-demand treatment cohort, 17 were assigned to group 1, 21 to group 2a, and 20 to group 2b. The estimated mean annualized rate of treated bleeding events was 0.57 (95% confidence interval [CI], 0.25 to 1.30) in group 2a and 0.20 (95% CI, 0.06 to 0.71) in group 2b, as compared with 15.76 (95% CI, 10.70 to 23.20) in group 1 (relative decrease, 96.4% and 98.7%, respectively; P<0.001 for both comparisons). Of the 196 patients in the pretrial prophylaxis cohort, 98 each were assigned to group 3 or group 4. The estimated mean annualized rate of treated bleeding events was 2.25 (95% CI, 1.37 to 3.71) in group 3, as compared with 4.90 (95% CI, 3.65 to 6.56) during the run-in phase (relative decrease, 54.0%; P = 0.006), and 1.78 (95% CI, 1.18 to 2.71) in group 4, as compared with 3.12 (95% CI, 2.25 to 4.32) (relative decrease, 42.8%; P = 0.0

This study aimed to evaluate the effect of the 'I Can Manage' an interactive web-based program that supports self-regulation under the leadership of nurses, application on self-management, fatigue and anxiety levels in individuals with Multiple Sclerosis (MS). This study is a parallel-group randomized controlled trial. Individuals with MS were randomly assigned to an intervention group (N = 38) and a control group (N = 38). The intervention group used 'I Can Manage' for eight weeks, while the control group did not receive any intervention. Data were collected using the Participant Identification Form, Multiple Sclerosis Self-Management Scale, Fatigue Severity Scale, State-Trait Anxiety Inventory, Program Usage Form, and Web Program Evaluation Form. The study was registered at ClinicalTrials database (NCT05393765). The time x group interaction for the self-management scores was significant and had a moderate effect size in favour of the intervention group (P < .01, pη2 = 0.114), whereas no significant changes were observed in the fatigue, state, and trait anxiety scores. A total of 86.8% of the participants used at least one feature of the program, and 93.9% found it easy to use and understand. 'I Can Manage' improved self-management in individuals with MS but did not lead to significant changes in fatigue or anxiety levels. © The Author(s) 2026. Published by Oxford University Press.

BACKGROUND: While dipeptidyl peptidase-4 inhibitors (DPP-4is) are linked to autoimmune skin diseases, comparative data on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) remain limited. METHODS: We emulated a randomized active-comparator trial using the TriNetX US Collaborative Network. Adults with type 2 diabetes (T2DM) initiating GLP-1 RAs or DPP-4is between January 1, 2018, and December 31, 2022, were identified, excluding prior users of either class. Balanced cohorts (n=169,630 each) were created using 1:1 propensity score matching. To address protopathic bias, outcomes occurring within 3 months after drug initiation were not considered. Patients were followed for up to 4 years for newly diagnosed autoimmune or inflammatory skin diseases. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with DPP-4i initiation, GLP-1 RA initiation was associated with a higher risk of incident psoriasis (HR 1.19, 95% CI 1.11-1.28) and lower risks of pemphigus (HR 0.32, 95% CI 0.16-0.63) and bullous pemphigoid (HR 0.61, 95% CI 0.43-0.87). No significant differences were observed for other inflammatory or autoimmune skin outcomes after multiple-testing correction. Findings persisted across subgroup and sensitivity analyses. CONCLUSION: In a large, real-world study designed to emulate a clinical trial, GLP-1 RAs were linked to increased psoriasis and decreased autoimmune blistering diseases compared with DPP-4is over up to 4 years' follow-up. These results provide a dermatologic safety context to guide incretin therapy selection and highlight the importance of ongoing skin monitoring.

PURPOSE: To primarily examine the feasibility of implementing eye-tracking-based feedback within a virtual reality (VR) trauma simulation with realistically simulated emergency department interruptions, and to explore preliminary changes in situational awareness (SA) (primary outcome), Advanced Trauma Life Support (ATLS) performance, and trauma-management errors (exploratory outcomes) compared with conventional mannequin-based simulation. METHODS: In this pilot randomized pretest-posttest study, 35 medical interns were assigned to VR training with eye-tracking heatmap feedback (n=17) or mannequin-based training with instructor verbal feedback (n=18). SA (modified Situation Awareness Global Assessment Technique), ATLS checklist performance, and trauma-management error scores were measured before and after the intervention. Within-group changes were tested with the Wilcoxon signed-rank test, and between-group differences were compared using the Mann-Whitney U test on change scores (Δ=post-pre), with effect sizes reported as r. RESULTS: Baseline pretest performance did not differ significantly between the groups. Both groups improved in SA and ATLS performance (all P<0.001) and reduced error scores (VR: P=0.004; mannequin: P<0.001). In exploratory between-group comparisons, the VR group showed numerically greater improvements in SA (mean change 6.59 vs. 3.11; P=0.006, r=0.46), ATLS performance (22.12 vs. 8.22; P=0.003, r=0.48), and error reduction (-9.36 vs. -3.61; P=0.005, r=0.47). Given the pilot design, these differences should be interpreted as preliminary signals. CONCLUSION: In this pilot study, both training modalities were associated with improved SA and ATLS performance and with fewer errors, with point estimates favoring the VR condition. These preliminary signals suggest that VR with eye-tracking feedback may be a promising option for trauma training in interruption-rich, emergency department-like settings and warrants further evaluation in larger studies.

Knee osteoarthritis (KOA) is a progressive degenerative joint disease with limited treatment options that effectively modify disease progression. This study evaluates the safety and efficacy of allogeneic adipose-derived mesenchymal stromal cells (ADMSCs) injected under ultrasound guidance in patients with symptomatic stage III KOA. In this single-site, randomized, double-blind, placebo-controlled trial, patients were assigned to receive either 2 doses of allogeneic expanded ADMSCs, administered 2 weeks apart (Arm A, mean total dose: 69.58 × 106 ADMSCs), or 2 equal-volume normal saline injections (Arm B). Blinding was maintained for 12 months, after which follow-up of Arm A continued to 60 months. Treatment efficacy was assessed using normalized Knee Injury and Osteoarthritis Outcome Score and Western Ontario and McMaster Universities Osteoarthritis Index at 6, 12, 24, 36, 48, and 60 months, while magnetic resonance imaging (MRI) evaluations were performed at baseline and 12 months. A total of 29 subjects (21 in Arm A, 8 in Arm B) completed the study. Adverse events in Arm A were mild and transient, including localized pain and swelling. Patients in Arm A demonstrated significant improvements in clinical scores compared to baseline, with highly significant differences at 6, 12, 24, and 36 months (P < .0001). MRI assessments at 12 months revealed structural improvement (P < .02). However, clinical improvements declined steadily after 36 months, with scores nearing baseline at 60 months. These findings suggest that allogeneic ADMSC therapy is safe and provides sustained clinical and structural benefits for up to 3 years. Larger trials are needed to optimize dosing and assess long-term efficacy. © The Author(s) 2026. Published by Oxford University Press.

Acid sphingomyelinase deficiency (ASMD) is a rare debilitating lysosomal storage disease resulting in multisystemic disease manifestations, significant disease burden, and early mortality for some individuals. Enzyme replacement therapy (ERT) with olipudase alfa (Xenpozyme) is the first disease-specific treatment indicated for noncentral nervous system manifestations of ASMD in children and adults. During the 1-year primary analysis of the ASCEND placebo-controlled trial in 36 adults with ASMD, olipudase alfa treatment reduced sphingomyelin storage and was associated with clinically significant improvements relative to placebo in multiple endpoints. An open-label extension of the ASCEND trial followed 35 of 36 adults during olipudase alfa treatment for up to 5 years. Mean time on olipudase alfa was 4.2 ± 1.0 years; mean compliance was 90% ± 13%. During long-term olipudase alfa treatment, percent predicted diffusing capacity for carbon monoxide (DLCO) increased (mean 50.1% ± 10.8% at baseline vs. 66.5% ± 13.3% at final assessment; mean change from baseline of 35.9% ± 27.5% (p < 0.0001). Mean baseline spleen volume of 11.5 ± 4.6 multiples of normal (MN) decreased to 4.8 ± 2.1 MN at final assessment, mean change from baseline -57.5% ± 10.1% (p < 0.0001) and mean baseline liver volume (1.5 ± 0.4 MN) decreased to 0.95 ± 0.23 MN at final assessment, (mean change from baseline -36.8% ± 11.5%, p < 0.0001). Plasma lyso-sphingomyelin levels decreased by 72% from baseline to final assessment. Overall, improvements in clinical parameters occurred regardless of baseline severity. No new safety issues emerged during the trial extension and 98% of treatment emergent adverse events were mild/moderate. Improvements in visceral ASMD disease with olipudase alfa treatment will significantly impact the disease burden for those with this progressive multiorgan disorder. © 2026 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.

Research suggests that domestic dogs (Canis lupus familiaris) living as pets within urban environments may experience challenges such as sensory overstimulation, limited agency, and hyper-dependence on humans. Such factors have been associated with the development of chronic stress within this population. While stress can be an adaptive response to internal or external challenges, chronic stress can have a negative impact on a dog's health, well-being and strain the human-animal bond. According to the American Society for the Prevention of Cruelty to Animals, 5.8 million domestic dogs and cats entered U.S. shelters, of which 607,000 were killed in 2024. Recent research indicates that behavioural issues remain among the most common reasons for relinquishment. Numerous studies identify chronic stress as an important yet often overlooked contributor to the development of problematic behaviours. Given the broad health and behavioural consequences of chronic stress, we argue that frameworks helping caregivers and communities recognize causes of stress and opportunities for mitigation are critically important. Moreover, sharing human environments exposes dogs to many of the same urban stressors, making dogs a particularly informative model for exploring mechanisms, detection, and mitigation of chronic stress relevant to both canine and human well-being. In this review, we briefly summarize current knowledge about the mechanisms and regulation of chronic stress in pet dogs, describe how prolonged dysregulation of stress-response systems affects health and behaviour, and review current physiological and behavioural indicators of chronic stress in dogs, discussing their present limitations. We consider existing evidence for the hypothesis that a sustained inability to satisfy species-specific, breed-specific, and individual needs across physiological, safety, social, and cognitive domains may be a major cause of chronic stress in dogs living in urban environments. Finally, we outline key directions for future research, including possible approaches for developing validated diagnostic and screening methods to measure chronic stress in pet dogs, systematic evaluation of in

135. Circ Genom Precis Med. 2026 Jun;19(3):e000101. doi: 10.1161/HCG.0000000000000101. Epub 2026 May 4. Detecting and Mitigating Bias for Inclusive and Trustworthy Clinical Research: A Scientific Statement From the American Heart Association. Zhong J, Al-Zaiti S, Bennett DA, Do S, Gaudino MFL, Gichoya JW, Musaad SMA, Narayan SM, Sajobi T, Shen Y, Armoundas AA; American Heart Association Data Science and Precision Medicine Committee of the Council on Genomic and Precision Medicine and Council on Clinical Cardiology; Council on Lifestyle and Cardiometabolic Health; Council on Hypertension; Council on Cardiovascular Radiology and Intervention. Bias in clinical research affects not only the internal validity of studies but also the equitable distribution of health benefits derived from studies. Among the most impactful forms are selection bias, attrition bias, and algorithmic bias, each of which is capable of distorting participant representation, treatment effect estimates, and model performance across important subgroups. This scientific statement provides a reference for cardiovascular researchers and clinicians, integrating detection, correction, and prevention strategies to address these biases. Selection bias may be mitigated through approaches such as inverse probability weighting and adjustment for sociodemographic imbalances; attrition bias can be addressed using intention-to-treat analyses and multiple imputation for missing data that are missing at random; algorithmic bias requires fairness-aware modeling, diverse training data sets, and explainable artificial intelligence techniques. These 3 forms of bias are not exhaustive, but their careful management is essential to achieving scientific rigor, fairness, and real-world applicability, and requires multidisciplinary collaboration to embed equity and validity throughout the research lifecycle.

Ketogenic dietary interventions (KDIs) are increasingly explored as adjuncts in oncology due to their metabolic and immunomodulatory effects. One mechanism by which KDIs are expected to modulate the immune system is by altering the gut microbiome, which has been shown to affect treatment outcomes, particularly in the context of immunotherapies. This review synthesized findings from 43 clinical trials to evaluate the current landscape of KDIs in cancer care, with a focus on the gut microbiota and immunotherapy. Although 47% of identified trials are completed, none have yet published results combining KDIs with immunotherapy. Since 2020, however, there has been a significant increase in ongoing studies investigating this combination and incorporating microbiome endpoints. While KDIs may help shape an immunotherapy-permissive environment, further clinical evaluation is necessary to determine the full extent of KDIs on the microbiome. Future research should prioritize longitudinal microbiome profiling and standardized adherence reporting to clarify the therapeutic potential of KDIs as a metabolic adjuvant to immune checkpoint inhibitors.

Appropriate bowel cleansing is essential for successful and safe colonoscopy. Inadequate bowel cleansing can lead to poor visualization of the delicate mucosa, leading to missed precancerous lesions, increased risk of procedure-related complications, and increased medical costs due to re-examination. Several types of bowel cleansing agents that improve ease of administration have been developed in recent years, and the clinical outcomes have been published. Bowel cleansing efficiency can differ between races due to differences in socio-environmental factors, including dietary patterns. This paper is the first Korean clinical guideline for bowel preparation for colonoscopy, formulated by the Korean Society of Gastrointestinal Endoscopy. These guidelines were developed using adaptation methods and the findings of studies on Korean patients; recently published studies were considered to the extent possible. These guidelines will be revised as and when new data regarding bowel preparation are accumulated.

BACKGROUND AND AIMS: Entecavir and tenofovir alafenamide fumarate are potent nucleos(t)ide analogues used to treat chronic hepatitis B; however, their differential effects on hepatitis B surface antigen expression decline remain unclear. In this multicentre study, we aimed to examine the hepatitis B surface antigen-reducing effects. METHODS: Treatment-naïve chronic hepatitis B patients who received entecavir (n = 491) or tenofovir alafenamide fumarate (n = 463) were enrolled. After 1:1 propensity score matching for sex, baseline hepatitis B surface antigen, hepatitis B e-antigen status, hepatitis B virus deoxyribonucleic acid, fibrosis-4 score, and the presence of hepatocellular carcinoma, data from 334 patients per group were analysed. Linear mixed-effects models were used to assess longitudinal changes over 4 years. RESULTS: Tenofovir alafenamide fumarate was associated with a greater decline in hepatitis B surface antigen compared to entecavir, with significant differences at 1, 3, and 4 years. Its superiority was most pronounced in patients aged < 65 years, those without cirrhosis, those with baseline hepatitis B surface antigen ≥ 3.0 log IU/mL, those with either negative or positive hepatitis B e-antigen, and those with baseline hepatitis B virus deoxyribonucleic acid < 4.4 log IU/mL. Both treatments achieved comparable virological suppression and alanine aminotransferase normalisation. The estimated glomerular filtration rate showed a transient decline with tenofovir alafenamide fumarate in year 1, which subsequently diminished and may partly reflect the inhibition of tubular creatinine secretion. CONCLUSIONS: This evidence supports personalised treatment selection for functional cure. TRIAL REGISTRATION: The UMIN Clinical Trials Registry 000034362. © 2026 John Wiley & Sons Ltd.

Virtual dissection tables such as Cadaviz offer interactive, 3D visualization of anatomical structures, potentially enhancing comprehension and engagement in medical education. This study examines how first-year MBBS students with diverse academic standings perceive the effectiveness of Cadaviz in supporting their anatomy learning. A cross-sectional survey was conducted with 220 first-year MBBS students at Sree Balaji Medical College, Chennai. Participants were stratified into Below-Average, Average, and Above-Average groups based on internal assessment scores. Perceptions of Cadaviz were assessed using a 20-question Likert-scale questionnaire covering effectiveness, engagement, interactivity, accessibility, usability, and perceived role of Cadaviz alongside traditional dissection. Data were analyzed descriptively and via one-way ANOVA to compare mean Likert Scale Scores across performance strata. Cadaviz was perceived as an effective anatomy learning tool, with below-average students reporting the greatest benefits in understanding structures, comprehension, and learning efficiency (p = 0.043-0.005). While traditional cadaveric dissection remained preferred, Cadaviz was valued as a supplement, enhancing engagement, interactivity, and self-paced learning. Students highlighted its accessibility, flexibility, and user-friendly interface, with fewer technical difficulties. Cadaviz fostered inclusive, learner-centered education, promoting active participation, conceptual understanding, and confidence across all academic strata, particularly supporting students needing additional reinforcement. © 2026 American Association of Clinical Anatomists and British Association of Clinical Anatomists.

Canine atopic dermatitis is a hereditary chronic inflammatory and pruritic skin disease, which is mediated by T cells and requires long-term, individualized management. In recent years, numerous studies have described a wide range of therapeutic approaches for canine atopic dermatitis, including fast-acting symptomatic treatments, long-term immune-modulating interventions, and strategies to support skin barrier function and microbial balance. This review summarizes the principal treatment modalities currently available, including glucocorticoids, cyclosporine A, mycophenolate, Janus kinase inhibitors, lokivetmab, and allergen-specific immunotherapy, as well as complementary strategies aimed at restoring skin barrier integrity. Emphasis is placed on the importance of a multimodal and personalized approach to optimize long-term disease control and improve quality of life in affected dogs. Providing an integrated overview of current evidence, this article aims to guide clinicians in making informed, evidence-based decisions and to support the safe and effective management of canine atopic dermatitis.

Hypovolemia is a systemic state characterized by severe reduction in the effective blood volume with subsequent tissue hypoperfusion. It may be due to fluid loss, decreased water intake, fluid redistribution, or systemic disease. The present study aimed to evaluate the diagnostic significance of the renal artery resistive index (RRI), caudal vena cava (CVC) diameter, and aorta (Ao) diameter in dogs with hypovolemia. For this purpose, 30 dogs (hypovolemic, n = 15; control, n = 15) were investigated. Clinical variables and hematological findings were investigated for each dog. Pulsed-wave Doppler ultrasound was performed to measure the RRI and diameters of the CVC and Ao. Ultrasound examination revealed a markedly elevated RRI (p < 0.001) and significantly reduced CVC (p < 0.001) and Ao (p < 0.001) diameters in hypovolemic dogs compared to controls, reflecting increased vascular resistance and impaired venous return. Biochemical analysis showed significant increases in blood urea nitrogen (BUN) and BUN:Cr ratio, while Cr remained unchanged. Hematological variables demonstrated limited diagnostic value, with only mild increases in packed cell volume (PCV%). Correlation analysis confirmed a strong positive correlation between RRI and BUN (r = 0.917; p < 0.01), RRI and BUN:Cr ratio (r = 0.664; p < 0.01), and CVC and Ao diameters (r = 0.832; p < 0.05). Receiver operating characteristic (ROC) analysis with area under the curve (AUC) identified RRI (AUC = 0.99), CVC diameter (AUC = 0.93), and Ao diameter (AUC = 0.88) as highly accurate markers of hypovolemia, whereas the CVC:Ao ratio and hematological markers provided poor discrimination. Logistic regression confirmed significant diagnostic value for RRI, CVC diameter, Ao diameter, and BUN, but final multivariate analysis revealed RRI as the sole independent early diagnostic marker (p < 0.001; OR: 196.0; 95% CI: 11.12-34.72). In conclusion, RRI measured by Doppler ultrasound is the most reliable and sensitive early diagnostic marker for hypovolemia in dogs, outperforming conventional biochemical and hematological markers.

Pasteurella multocida (P. multocida) is not only the core pathogen of bovine respiratory disease (BRDC) but also a significant zoonotic agent, posing a dual threat to global animal husbandry and public health. This study utilized untargeted metabolomics to systematically dissect the metabolic regulatory network of P. multocida in response to tylosin within a One Health framework. The results revealed significant "defense-growth" metabolic reprogramming: activation of amino sugar and nucleotide sugar pathways (e.g., CDP-glucose) indicated cell wall remodeling, while directional shifts in the phenylalanine-tyrosine network directed flux toward defensive secondary metabolites. Concurrently, amino acid disorders and the overactivation of the ABC transporter system exacerbated an internal energy crisis, characterized by a shift from respiration to glycolysis, ATP depletion, and ROS accumulation. SEM observations confirmed membrane integrity disruption and cytoplasmic leakage. Crucially, this metabolic stress and the transition into a "persister-like" dormant state are closely linked to the adaptive expression of antimicrobial resistance (AMR) genes. Under the selective pressure of tylosin, these metabolic perturbations may facilitate the emergence and horizontal transfer of resistance determinants, which can circulate through the animal-human-environment interface. By revealing the metabolic physiological basis of tylosin's action and its role in inducing bacterial tolerance, this study provides critical theoretical insights for antimicrobial stewardship, aiming to mitigate the risk of AMR transmission and preserve the efficacy of macrolides for both veterinary and human medicine.

West Nile virus (WNV) is a mosquito-borne flavivirus of growing importance for both human and equine health in Europe. Horses are highly susceptible to neurological disease and, because they share ecological exposure with humans, they represent valuable sentinels for detecting local viral circulation within a One Health framework. However, diagnosis of WNV infection in equines is complicated by the short and low-level viraemia, which limits the sensitivity of molecular assays, and by serological cross-reactivity with related flaviviruses and the confounding effects of vaccination. In this narrative review, we summarise the current diagnostic tools for WNV in horses, including direct detection methods (RT-qPCR, virus isolation, antigen detection) and indirect serological approaches (IgM and IgG ELISA, virus neutralisation tests), and discuss their practical performance and constraints in clinical and surveillance settings. We further examine equine surveillance systems, passive clinical reporting, active serosurveys and sentinel cohorts, and their integration with vector, avian and environmental monitoring. Key challenges include methodological heterogeneity, limited access to confirmatory testing and variable cross-sector data sharing. Finally, we outline future directions, highlighting the need for harmonised laboratory protocols, innovative field-deployable diagnostics, genomic surveillance and integrated, multi-source monitoring systems to strengthen early warning capacity and improve preparedness for WNV outbreaks in equine populations.