Botulinum toxin type A (BoNT-A) is globally recognized as a standard treatment for post-stroke spasticity (PSS), although its secondary mechanisms remain underinvestigated. The objective of this study was to investigate the neurophysiological mechanisms underlying BoNT-A treatment in PSS and explore their implications for mechanism-based rehabilitation.

A systematic review and meta-analysis (PROSPERO registration number ID: CRD420261352230) of 39 studies involving 760 patients was conducted on 18 August 2026, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Web of Science, Scopus, and Embase were systematically searched using the PICO framework. Where possible, quantitative data were pooled according to predefined neurophysiological constructs, including passive stretch-evoked activity, voluntary activation of the injected muscle, compound muscle action potential (CMAP), reciprocal motor control, normalized Hmax/Mmax, and specific spinal inhibitory mechanisms.

Quantitative synthesis demonstrated construct-specific neurophysiological changes following BoNT-A treatment. Passive stretch-evoked activity showed the largest pooled effect (Hedges' g = 0.80, 95% CI 0.35-1.24), followed by CMAP amplitude (g = 0.69, 95% CI 0.23-1.14) and reciprocal motor control (g = 0.52, 95% CI 0.23-0.81). Effects on voluntary activation of the injected muscle (g = 0.31, 95% CI -0.38 to 1.00) and normalized Hmax/Mmax (g = 0.22, 95% CI -0.74 to 1.17) were smaller and more heterogeneous. Reciprocal and recurrent inhibition were each represented by single-study estimates, while supraspinal outcomes were synthesized narratively due to methodological heterogeneity.

The findings support a predominantly peripheral mechanism of BoNT-A while suggesting possible secondary changes within spinal and supraspinal motor control pathways. However, the certainty of evidence was low to very low. These neurophysiological effects provide a rationale for individualized, mechanism-based rehabilitation during the post-injection therapeutic window, although higher-quality evidence is required to confirm this framework.

This narrative review synthesizes a comprehensive multimodal characterization framework for atrial fibrillation (AF), tracing its progression from patient-specific anatomical reconstruction to electrophysiological phenotyping and standardized spatial mapping. The literature was identified through searches of PubMed, Web of Science, and Google Scholar, covering publications from January 2010 to June 2026, with additional studies identified from relevant references. Anatomical characterization leverages clinical imaging modalities alongside advanced deep learning models to execute precise whole-chamber, subregional, and tissue-level modeling. Electrophysiological profiling spans multi-scale modalities, including 12-lead electrocardiography (ECG), body surface potential mapping (BSPM), electrocardiographic imaging (ECGI), and electroanatomical mapping (EAM), complemented by wearable sensors for longitudinal rhythm surveillance. To bridge heterogeneous datasets across subjects and modalities, standardized coordinate systems and multimodal registration enable reproducible data integration. These integrated data parameterize patient-specific computational models to advance mechanistic insight, risk stratification, and personalized AF management. However, broad clinical translation remains constrained by imaging variability, reconstruction noise, registration uncertainty, and limited prospective multicenter validation. Future progress hinges on moving beyond technical accuracy toward prospective trials evaluating algorithm-guided clinical utility.

A multicentre, laboratory-based analysis was conducted on aggregated data from 23 hospitals across Colombia. Of 1761 fungal isolates identified, 1642 were yeasts and constitute the focus of this study. Isolates were identified using the VITEK^®2 system, with confirmatory identification by MALDI-TOF-MS for a subset. Antifungal susceptibility testing for fluconazole, voriconazole, amphotericin B, and the echinocandins was performed on Candida albicans, C. parapsilosis, and C. tropicalis. Data were stratified by clinical service: adult ICU, adult wards, paediatric ICU, neonatal ICU, and paediatric wards. Temporal trends were assessed using the Cochran-Armitage test. The most prevalent species were C. albicans (42%), C. parapsilosis (24%), C. tropicalis (11%), C. glabrata (7%), and C. auris (3%). C. albicans predominated in adult services, whereas C. parapsilosis was the leading pathogen across paediatric settings. Among species with validated breakpoints, the overall fluconazole resistance rate was 19%, driven primarily by C. parapsilosis (35%, exceeding 40% in some clinical services). Non-wild-type to voriconazole and amphotericin B was low (<5%), and echinocandin resistance was exceedingly rare. The substantial fluconazole resistance driven by C. parapsilosis, together with the emergence of C. auris, underscores the urgent need for sustained surveillance and species-directed antifungal stewardship programmes.

Isaridin E (ISE), a marine-derived fungal cyclodepsipeptide, possesses antiplatelet activity in vitro and antithrombotic efficacy in a FeCl₃-induced carotid artery thrombosis mouse model without prolonging bleeding time. In this study, we investigated the antiplatelet and neuroprotective effects of prophylactic and therapeutic administration of ISE in a transient middle cerebral artery occlusion (tMCAO) mouse model. We found that both prophylactic administration (50 and 100 mg/kg) and therapeutic administration (50 mg/kg) of ISE significantly reduced cerebral infarct volume, alleviated neurological deficits, and attenuated neuronal injury. Furthermore, therapeutic administration of ISE suppressed platelet hyperactivity, as evidenced by reduced P-selectin expression, downregulated platelet secretion-related proteins (SNAP23, VAMP8), and decreased plasma levels of platelet-derived pro-inflammatory cytokines (IL-1β, PF4, and CCL5). Moreover, ISE attenuated microglial inflammatory activation in the peri-infarct region in vivo. Mechanistically, in vitro studies revealed that this effect may be mediated through the LRP1/IκB/NF-κB signaling pathway. In conclusion, these results suggest that ISE protects mice against ischemic stroke by concurrently suppressing platelet hyperactivity and LRP1-associated microglial neuroinflammation.

Hyperlipidemia is a chronic metabolic disorder in humans, contributing to the onset of cardiovascular diseases (CVDs) that remain the leading cause of death worldwide. Current clinical antihyperlipidemic agents are often accompanied by diverse adverse side effects. Therefore, developing safer novel lipid regulators is an urgent and challenging task. Marine polysaccharides exhibit remarkable antihyperlipidemic activity owing to their distinctive physicochemical properties, multi-target mechanisms, and system-level modulation. This review systematically summarizes recent progress regarding the antihyperlipidemic efficacy of marine polysaccharides and provides comprehensive insights into their sources, structural features, structure-activity relationships, mechanisms of action, and application potential. Furthermore, this review also highlights the existing limitations and challenges in translational research of marine polysaccharides, and puts forward future research directions to advance marine polysaccharides into safe, effective, and sustainable natural therapeutics for hyperlipidemia.

Microplastics and nanoplastics (MNPs) have emerged as widespread environmental contaminants, with increasing evidence suggesting that chronic exposure may adversely affect human health. Experimental and emerging human studies indicate that MNPs can interact with multiple biological systems and trigger a range of mechanisms, including oxidative stress, mitochondrial dysfunction, cellular injury, barrier disruption, and immune and inflammatory responses. These effects may involve direct interactions with tissues and cells as well as indirect pathways, including alterations in gut microbial and intestinal homeostasis. In turn, persistent inflammatory and metabolic disturbances may contribute to tissue dysfunction and the development or progression of chronic diseases. This narrative review summarizes current evidence on the biological effects of MNP exposure, focusing on the mechanisms linking environmental exposure to chronic inflammation and disease. We discuss their potential involvement in cardiovascular, liver, kidney, respiratory, and neurological diseases, while highlighting the emerging role of the gut microbiota and intestinal barrier as potential modulators of these effects. Given the limitations of current human evidence and the heterogeneity of experimental models, we also discuss major knowledge gaps and the need for further mechanistic and epidemiological studies to clarify the clinical relevance of chronic MNPs exposure.

Background and aims. Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease associated with cirrhosis, hepatocellular carcinoma, and increased risks of liver-related and cardiovascular mortality. Many patients, however, remain asymptomatic until advanced stages. The gamma-glutamyl transferase to high-density lipoprotein cholesterol (GGT/HDL-C) ratio is a simple, noninvasive marker reflecting hepatic dysfunction and cardiometabolic imbalance. This study assessed its association with NAFLD and determined an optimal cutoff for identifying NAFLD. Methods. We conducted a cross-sectional analysis of 575 adults undergoing routine health examinations at the University of Medicine and Pharmacy Hospital in Ho Chi Minh City between 2021 and 2023. Participants with significant alcohol intake, viral hepatitis, or other chronic liver diseases were excluded. NAFLD was diagnosed by standardized abdominal ultrasonography based on increased hepatic echogenicity relative to the renal cortex or spleen. Associations between GGT/HDL-C and NAFLD were assessed by logistic regression (both as a continuous variable and by quartiles), and diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Statistical significance was defined as a two-tailed p-value < 0.05. Results. Individuals with NAFLD showed significantly higher BMI, prevalence of hypertension and diabetes, and elevated glucose, HbA1c, AST, ALT, GGT, cholesterol, triglycerides, and LDL-C, along with lower HDL-C. Each unit increase in the GGT/HDL-C ratio was associated with a 2% increase in the odds of NAFLD based on univariate logistic regression analysis. However, after adjustment for demographic and metabolic covariates, the GGT/HDL-C ratio was no longer independently associated with NAFLD. The highest quartile had an odds ratio of 7.05 (95% CI: 4.2-11.83) compared to the lowest. The area under the ROC curve for GGT/HDL-C was 0.72, outperforming GGT or HDL-C alone. A cutoff of 32.47 UI/mmol had 72.4% sensitivity and 63.3% specificity. Conclusions. The GGT/HDL-C ratio showed a significant unadjusted association with NAFLD and moderate discriminatory performance. However, because the association was no longer significant after full adjustment, the ratio should currently be considered a simple laboratory-based screening marker that requires further validation before routine clinical application.

Background/Objectives: Clinical teaching as a form of interpersonal education organized in a real clinical setting is very dynamic and sensitive to many factors that may influence its effectiveness. To strengthen clinical education organization, responsible bodies should meet emerging challenges, which are best understood from the perspective of the direct recipients and providers of clinical teaching. Therefore, the aim of this study was to explore and analyze the existing challenges of clinical teaching organization in public medical universities in Poland from students' and academics' perspectives. Methods: A modified two-round Delphi study was conducted in six Polish medical universities. Round 1 included 218 experts (131 students and 87 academics), while 124 experts completed Round 2 (attrition rate: 43.1%). Consensus was predefined as a median score ≥ 4.0 and IQR ≤ 1.0. Results: Items with the highest mean values (approximately 4.4 on a five-point Likert scale) indicated a clear perception of space shortages and demand for updated teaching methods. The exploratory correlation revealed two broad thematic patterns: (1) space and overcrowding; (2) teaching methods. Conclusions: The findings suggest that stakeholders perceive educational space, overcrowding and modernization of teaching methods as important areas for improvement in clinical teaching.

Metabolic syndrome (MetS) increases susceptibility to myocardial ischemia/reperfusion (I/R) injury through metabolic disturbance, hypertension, and oxidative stress. This study aimed to compare the effects of liraglutide and semaglutide on post-ischemic cardiac function, oxidative stress, and histomorphological changes in rats with MetS.

MetS was induced in male Wistar rats by a high-fat diet followed by low-dose streptozotocin. After confirmation of MetS, animals were treated with saline, liraglutide, or semaglutide for 6 weeks. Blood pressure, glycemia, oral glucose tolerance, and lipid profile were assessed during the protocol. In vivo cardiac function was evaluated by echocardiography, whereas ex vivo I/R injury was induced using the Langendorff technique. Cardiodynamic parameters, coronary flow, oxidative stress markers, and histological changes in the heart, liver, and pancreas were analyzed.

Both liraglutide and semaglutide improved the cardiometabolic profile of MetS rats, with semaglutide showing a more evident effect on body weight control. In the Langendorff model, both treatments improved post-ischemic recovery of myocardial contractility and relaxation during reperfusion. Treated animals also showed a more favorable oxidative stress profile, particularly lower superoxide anion levels and enhanced antioxidant defense. Histologically, both agents attenuated myocardial hypertrophy and collagen deposition, improved hepatic architecture by reducing inflammatory changes, and preserved pancreatic structure with less lipid accumulation and tissue injury.

Liraglutide and semaglutide exerted significant cardioprotective and tissue-protective effects in experimental MetS complicated by myocardial I/R injury. These findings support their potential in limiting post-ischemic cardiac dysfunction and multiorgan damage in metabolically compromised conditions.

Background: Bicuspid aortic valve disease (BAVD) is the most frequent congenital heart disease, occurring either as an isolated lesion or in association with other congenital cardiovascular malformations, with variable patterns of progression and risk of valvular and vascular complications. Studies addressing pediatric bicuspid aortopathy are still in their infancy. This narrative review aims to provide a comprehensive perspective on the current scientific evidence regarding BAVD-associated aortopathy in pediatric patients, underscoring multiple challenges in initial diagnosis, long-term surveillance, and therapeutic decision-making, and focusing on the potential roles of circulating biomarkers and advanced multimodal imaging tools that may improve individualized risk stratification. Methods: Despite the narrative design of this review, a structured search of the current available literature was performed to identify studies addressing pediatric BAV, associated aortopathy, biomarkers, vascular remodeling, and multimodal imaging. Priority was given to pediatric cohorts, longitudinal studies, consensus documents, and contemporary guidelines. The search was conducted in the online databases PubMed/Medline and Web of Science for English-language original articles published in the last 10 years, up to May 2026. We used the following main terms: "Bicuspid Aortic Valve Disease" [MeSH], "Aorta" [MeSH], "Infant" [MeSH], "Child" [MeSH], "Adolescent" [MeSH], combined by Boolean operators with secondary keywords: "pathogenesis", "mechanism", "progression", "multimodal imaging", "echocardiography", "cardiovascular magnetic resonance imaging", "computed tomography", "circulating biomarkers". The retrieved studies were screened for eligibility using previously established inclusion and exclusion criteria. A total of 63 studies were included in the analysis for this narrative review. Results: Two main theories underpin the etiopathogenesis of aortopathy associated with the bicuspid aortic valve, positing that genetic factors predispose the aortic wall to remodeling in an abnormal hemodynamic environment. Embryological development and dysregulation of molecular and cellular structures are also intertwined during the formation and progression of the aortic valve with two semilunar cusps, resulting in consequent alterations in the aortic wall's architectural organization. Advances in molecular studies have highlighted circulating biomarkers with potential utility in predicting aortopathy, as they are involved in extracellular matrix remodeling, endothelial dysfunction, and aortic valve calcification, including matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), transforming growth factor-β (TGF-β), and microRNAs. In addition, multimodal imaging techniques have emerged as essential tools for assessing the morphology and function of cardiovascular structures, particularly aortic biomechanical properties and hemodynamic abnormalities, at the time of initial diagnosis and during regular monitoring. Taken together, blood biomarkers and imaging parameters of aortic remodeling and flow disturbances might gain increasing prognostic value in pediatric BAVD-associated aortopathy. However, larger longitudinal studies are required for clinical validation beyond research settings. Although guidelines on the management of BAVD are available for adults, they are not entirely applicable to children, who are undergoing continuous somatic growth that affects diagnostic possibilities and therapeutic options. Conclusions: Despite growing literature in the realm of BAVD and related conditions, the management of pediatric patients remains challenging in daily clinical practice, as adult guidelines cannot be completely applied to children. Given the heterogeneity and complexity of pathogenic mechanisms, clinical presentations, natural history, and outcomes, future research is warranted to explore the progression profiles of valvular and vascular disorders associated with BAV in children and to achieve an optimal approach to pediatric bicuspid aortopathy.