Purpose: To determine relationships between mobility capacity and walking performance in older adults with outdoor walking limitations. Method: This cross-sectional study involved secondary analysis of baseline data from the Getting Older Adults Outdoors (GO-OUT) study (115 females, 53 males; mean age of 74.6 [SD 7.0] years). Mobility capacity tests included 6-minute walk test (6MWT), 10-metre walk test (10MWT), 30-second sit-to-stand (30sSTS), and Mini-BESTest. Walking performance included peak 30-minute cadence, time walked in bouts, and steps per day (accelerometry). Multiple linear regression was used to determine associations between capacity and performance, adjusted for age, sex, and comorbidity. Results: Individual measures of mobility capacity were significantly associated with all measures of walking performance, explaining variances of 24%-28% in peak 30-minute cadence, 9%-14% in time walked in bouts, and 18%-22% in steps per day. In combined models, 6MWT and 30sSTS were significantly associated with peak 30-minute cadence (R 2 = 0.37), 10MWT with time walked in bouts (R 2 = 0.15), and 30sSTS with steps per day (R 2 = 0.25). Conclusions: Relationships between mobility capacity and walking performance vary depending on chosen measure of performance. Lower extremity muscle endurance, muscle strength, cardiovascular capacity, and balance are important for walking in everyday life.

Beauvericin (BEA), enniatin B (ENN B), and moniliformin (MON), mainly produced by Fusarium species, are often described as emerging mycotoxins due to their frequent detection in cereals and cereal-based products and their current lack of regulatory limits. Despite increasing evidence regarding their individual toxicities-including immunotoxic, genotoxic, reproductive, and cardiotoxic effects-information on their combined toxicity and the underlying mechanisms remains limited. To address this gap, this study aimed to evaluate the cytotoxic effects, reactive oxygen species (ROS) generation, and interaction patterns of BEA, ENN B, and MON in human Jurkat T cells following a 24-hour exposure under individual, dual, and triple treatment conditions.

Purpose: Dry needling (DN) regulations among the Canadian physiotherapy colleges were compiled to make recommendations toward a national guideline. Method: DN regulatory data extracted from regulatory body websites using an environmental scan framework was checked by an independent reviewer. Colleges were contacted to fill gaps identified from the web. Extracted content was compared to recommendations from two Canadian DN reviews to identify gaps in regulation. Results: DN regulation is done through legislation (two colleges), practice guidelines (one), or both (seven), depending on the college and its provincial or territorial jurisdiction. Three colleges have prerequisites for DN courses, four have approved DN courses, nine require specific course content, three require minimum course hours, nine require registration or rostering, and three have continued competency expectations. No colleges have evidence-based guidelines to inform requirements or meet all DN recommendations. Conclusions: Heterogeneity in regulation likely represents gaps that may potentially expose the public to risk. Physiotherapy colleges could review their regulatory process, address these gaps if they are deemed related to increase risk, and ultimately come to a consensus on what are the safest regulations of practice for Canadian physiotherapists.

Background American football has the highest injury rate of any U.S. high school sport, yet most studies examine a single injury type or position. We characterized injury patterns among high school football athletes in Long Island, New York, over five consecutive seasons, focusing on how injury patterns vary by level of play, setting, and position. Methods In this retrospective cohort study, certified athletic trainers and sports medicine physicians documented all in-season injuries among varsity and junior varsity (JV) athletes at 16 high schools from 2019 to 2023. Level of play, setting, mechanism, anatomic location, diagnosis, position, and time to return to play were recorded. Proportions were compared using two-sample Z-tests for independent proportions, with a two-sided p < 0.05 considered significant. Test statistics are reported as Z values alongside exact p-values. Results Among 3,861 athletes (2,093 varsity, 54.2%), 1,476 injuries were recorded. Varsity athletes accounted for a greater share of injuries than JV athletes (n = 1,104, 74.8% vs. n = 372, 25.2%; Z = 26.95, p < 0.001). Most injuries occurred in games despite far more practices (n = 732 of 1,308 injuries with setting recorded, 56.0%; Z = 6.10, p < 0.001). Direct contact was the leading mechanism (n = 796 of 1,344 injuries with the mechanism recorded, 59.2%). The lower extremity was most often injured (n = 672, 45.5%), followed by the upper extremity (n = 431, 29.2%) and head/neck (n = 187, 12.7%). Concussion was the most common specific diagnosis (n = 131, 8.9%). Profiles differed by position: offensive linemen had the highest proportion of concussions, and linebackers had the highest proportion of contact-related injuries. The proportion of athletes with a recorded concussion did not differ between varsity and JV athletes (Z = 0.53, p = 0.594). Conclusions A greater proportion of recorded injuries occurred among varsity athletes, in games, and through direct contact. Injury profiles differed by position, most notably a high proportion of concussions among offensive linemen. Because athlete exposure denominators were unavailable, these findings describe the distribution of recorded injuries rather than exposure-adjusted risk. These multiyear, position-specific data can inform targeted prevention and safety policy in high school football.

High-energy bicondylar tibial plateau fractures of Schatzker types V and VI are conventionally managed, after open reduction and internal fixation, with 6-12 weeks of restricted weight-bearing, out of concern for loss of reduction and articular collapse. Emerging evidence questions whether this restriction is necessary. Reports of immediate weight-bearing specifically after fixation of these most unstable bicondylar patterns remain scarce, as most comparative studies pool this subtype within mixed cohorts. We present three consecutive patients (two men and one woman; mean age: 54 years; all of North Indian ethnicity) with closed, high-velocity Schatzker type V-VI tibial plateau fractures sustained in road traffic accidents. Each was treated with open reduction and internal fixation using a dual-plate or three-plate construct, with allograft impaction of the metaphyseal void created after the elevation of the depressed articular fragments. In departure from the conventional restricted protocol, each patient was mobilised to full weight-bearing as tolerated from the first postoperative day, using a walking aid for balance rather than for offloading, with early active range-of-motion exercises and no brace. At six weeks, all three patients had achieved independent ambulation with a walking aid, knee flexion beyond 90 degrees, no pain during activities of daily living, and a clinically acceptable gait. Follow-up radiographs showed no loss of fixation, screw cut-out, or articular collapse, and no patient sustained a wound complication, infection, or revision surgery. Immediate unrestricted full weight-bearing after stable plate fixation of Schatzker type V-VI tibial plateau fractures appears safe and may accelerate functional recovery. These observations are concordant with recent randomised and comparative literature and are underpinned by a coherent bone-biological rationale in which physiological loading promotes rather than jeopardises union. This report supports a considered shift away from routine prolonged non-weight-bearing towards individualised, stability-guided early mobilisation, even for the most unstable bicondylar patterns, provided the fixation construct is intraoperatively judged sound. Larger prospective comparative studies are needed to confirm these findings and refine patient selection.

Background and Study Aims The depth of early gastric cancer is an important factor in determining treatment plans, such as endoscopic resection or surgery. We developed an artificial intelligence (AI) program using deep neural networks to diagnose mucosal and submucosal cancers via endoscopic images. Performance evaluation tests were conducted for its clinical applications. Patients and Methods A test dataset comprising 204 early gastric cancer cases treated with endoscopic resection or surgery at our hospital between 2018 and 2021 was established. A minimum of five white-light imaging (WLI) images per case were used (median, 8; range, 5-22). The primary endpoint was the sensitivity for diagnosing mucosal cancer. The AI program was defined as useful when the lower limit of the 95% confidence interval (CI) exceeded 75%, based on previous reports on the depth diagnosis of early gastric cancer. Secondary endpoints were specificity and accuracy. Results In our study, the sensitivity of this program for the diagnosis of mucosal cancer was 91.2%, and the lower limit of the 95% CI of sensitivity was 85.2%, which was higher than 75%, indicating the usefulness of this program. The specificity and accuracy were 66.2% and 82.8%, respectively. Conclusions The AI program developed to diagnose the depth of early gastric cancer is useful and expected to be clinically applicable.

The clinical translation of cancer nanomedicine remains constrained by inefficient intracellular delivery, poor subcellular specificity, and limited tumor accumulation, highlighting the need for more precise drug delivery strategies. Organelle-targeted nanocarriers have emerged as a promising platform for enhancing therapeutic efficacy by directing drugs to specific intracellular compartments, including the nucleus, mitochondria, lysosomes, and endoplasmic reticulum. However, the design principles governing efficient organelle-specific delivery and the barriers limiting clinical translation remain incompletely understood. This review provides a mechanistic framework linking nanoparticle physicochemical properties-including size, surface charge, ligand functionalization, and stimuli responsiveness to intracellular trafficking, organelle targeting, and therapeutic performance. We critically discuss the biological barriers encountered during delivery, including cellular uptake, endosomal escape, cytosolic transport, and organelle membrane penetration, together with current engineering strategies to overcome these challenges. Organelle-specific targeting approaches are comparatively evaluated to highlight their therapeutic advantages, limitations, and suitable clinical applications. Beyond summarizing recent advances, this review examines the major translational hurdles that impede clinical implementation, including non-specific biodistribution, manufacturing scalability, regulatory challenges, and the lack of standardized preclinical evaluation models. Emerging solutions such as hierarchical targeting, charge-reversal systems, size-transformable nanocarriers, and multifunctional theranostic platforms are discussed as strategies to improve clinical feasibility. Finally, we propose practical design guidelines and future research priorities that integrate nanomaterial engineering, predictive biological models, and scalable manufacturing to facilitate the development of clinically translatable organelle-targeted nanomedicines.

Melatonin regulates inflammation and oxidative stress at the placenta, but its effects on specific placental cell types remain unclear. This study investigated how melatonin influences inflammatory and oxidative stress responses, cytokine secretion, NRF2-associated antioxidant responses, and transcriptomic responses in JEG-3 trophoblast-like cells and primary decidual macrophages exposed to lipopolysaccharide (LPS). Melatonin reduced LPS-induced inflammatory cytokine production and intracellular reactive oxygen species accumulation, with pretreatment producing the strongest anti-inflammatory effects. Although NLRP3 transcript expression differed according to treatment sequence, melatonin was associated with reduced inflammatory cytokine secretion despite limited changes in total NLRP3 protein expression. Melatonin also differentially influenced antioxidant responses across placental cell types, with decidual macrophages exhibiting broader functional and transcriptional changes than JEG-3 trophoblast-like cells. Transcriptomic profiling revealed dose- and cell type-dependent effects, with decidual macrophages exhibiting altered expression of genes and pathways associated with inflammatory signaling, oxidative phosphorylation, and reactive oxygen species regulation. In contrast, JEG-3 trophoblast-like cells demonstrated limited transcriptional remodeling and more modest engagement of inflammatory signaling pathways than primary decidual macrophages. These findings suggest that melatonin differentially modulates inflammatory and oxidative stress responses across placental cell types at the maternal-fetal interface. Collectively, these data support the potential role of melatonin in promoting placental redox-inflammatory balance during inflammatory stress and provide a foundation for future studies in physiologically relevant models.

Knee osteoarthritis (KOA) is a leading cause of chronic pain and physical disability in the aging global population, placing an immense burden on healthcare systems. Despite its rising incidence, clinical practice and research remain disproportionately focused on late-stage joint replacement, neglecting early-stage preventive and conservative care for high-risk individuals. To address this gap, this narrative review searched major databases including PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library for clinical guidelines, high-quality systematic reviews, and randomized controlled trials focusing on non-surgical interventions for early KOA and high-risk populations. Search terms included "early knee osteoarthritis," "non-surgical treatment," "exercise therapy," and "weight management". Literature analysis demonstrates that a structured, "lifelong, stepped" non-surgical paradigm yields significant clinical efficacy. Specifically, combining dietary weight loss with physical exercise optimally reduces mechanical joint loading and systemic inflammatory markers; targeted muscle strengthening, alongside mind-body exercises like Tai Chi or yoga, improves the joint microenvironment and neuromuscular control; biomechanical orthoses and physical therapies offer substantial short-term pain relief; and topical or systemic NSAIDs combined with intra-articular injections effectively manage refractory acute symptoms. Crucially, continuous clinical supervision and structured patient education are vital for enhancing long-term treatment adherence and delaying radiological disease progression. Ultimately, implementing early, proactive non-surgical interventions, grounded in patient education and integrating weight management, targeted exercise, and multimodal stepped therapies, effectively alleviates pain, restores physical function, and delays or entirely prevents the need for future joint replacement.