Perimenopause is a natural physiological transition associated with declining ovarian function and bothersome systemic symptoms. Menopausal hormone therapy (HT) remains the primary treatment, but safety concerns persist. Commercial Chinese polyherbal preparations (CCPPs) combined with HT are increasingly used, yet comparative evidence remains limited. This network meta-analysis (NMA) evaluated the effectiveness and safety of CCPPs plus HT for perimenopausal symptoms. Chinese and English databases were searched for randomized controlled trials (RCTs) evaluating CCPPs plus HT. The study followed the reporting guideline for network meta-analyses and was registered in PROSPERO (CRD420261335785). Risk of bias was assessed using the revised Cochrane risk-of-bias tool. Data were synthesized in Stata 18.0, and surface under the cumulative ranking curve values were estimated as exploratory summaries. Seventy-three RCTs (n = 8,314) involving 11 CCPPs were included. Most studies had some concerns or high risk of bias, mainly owing to inadequate blinding and subjective-outcome vulnerability. Five CCPP + HT regimens significantly reduced the Kupperman Index (KI) compared with HT alone. Linglianhua Granule plus HT showed the largest KI estimate, but was supported by only two trials and low-certainty evidence. Given the very large standardized mean differences and the subjective nature of KI assessment in mostly unblinded trials, these results should be interpreted cautiously. For the Menopause-Specific Quality of Life questionnaire, only Kuntai Capsule plus HT showed significant improvement. The overall effective rate was treated as auxiliary because definitions varied. Dingkun Pill plus HT and Kuntai Capsule plus HT showed favorable estimates versus HT alone for estradiol elevation and follicle-stimulating hormone/luteinizing hormone reduction, respectively. CCPP + HT did not significantly increase reported short-term adverse reactions, but monitoring and follow-up were insufficient to establish safety superiority, equivalence, or long-term safety. CCPP + HT may be associated with improvements in selected symptom-related and endocrine outcomes compared with HT alone, but the evidence was generally of low to moderate certainty and derived mostly from unblinded trials. Ranking results, particularly for KI, should be considered exploratory summaries and not clinically actionable treatment hierarchies. Further high-quality blinded RCTs with standardized outcome assessment, adverse-event monitoring, and longer follow-up are needed. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261335785, identifier CRD420261335785.
Hypertension guidelines generally recommend uniform sodium restriction although determinants of salt sensitivity, or sodium-blood pressure responsiveness, remain incompletely quantified. We estimated the population sodium-blood pressure dose-response, identified clinical modifiers, quantified high salt sensitivity prevalence, and derived the number needed to restrict sodium intake to prevent 1 cardiovascular event across clinical strata. PubMed, Embase, and Cochrane were searched from inception to April 2025 for sodium intervention trials and observational studies. Blood pressure response was standardized per 50-mmol/d sodium difference. Random-effects metaregression evaluated clinical modifiers. A highly salt-sensitive phenotype was defined a priori as a systolic blood pressure (SBP) decrease ≥3 mm Hg per 50-mmol/d reduction. We included 160 studies (255 estimates; n=16 443). Each 50-mmol/d higher urinary sodium excretion was associated with 1.76-mm Hg higher SBP (95% CI, 1.54-1.98). Age and baseline SBP were the strongest modifiers (0.41 mm Hg per 5 years; 0.23 mm Hg per 5 mm Hg). Salt-sensitive phenotype prevalence rose from 12.5% (age <40 years) to 56.5% (>60 years) and from 16.3% (SBP <120 mm Hg) to 54.1% (≥130 mm Hg). Under a policy-relevant 100-mmol/d sodium reduction, number needed to restrict ranged from ≈1334 in younger, normotensive, lean individuals (age <60 years, SBP <130 mm Hg, and body mass index <25 kg/m2) to ≈87 in older adults with hypertension and elevated body mass index (age ≥60 years, SBP ≥130 mm Hg, and body mass index ≥25 kg/m2), a 15-fold gradient. Salt sensitivity varied across age, SBP, and body mass index strata. These findings suggest that routinely measured clinical characteristics may help identify populations with greater expected blood pressure response to sodium reduction.
Recreational ketamine use is rapidly increasing, and ketamine-induced uropathy (KIU) is gaining recognition for its severe impact on quality of life (QoL), including pain, hematuria, lower urinary tract symptoms (LUTS), and potential negative effects on sexual function. This study investigates the prevalence of sexual dysfunction among men with KIU. Male patients with KIU completed the International Index of Erectile Function (IIEF-5 and/or IIEF-15). Erectile dysfunction (ED) was defined as a score of ≤21 on IIEF-5 or ≤ 25 on domain A of IIEF-15. Patients who had not been sexually active in the previous four weeks (a score of 0 on IIEF-5 or within any domain of IIEF-15) were excluded. The impact of LUTS on sexual life and its perceived severity were assessed using items 10a and 10b of the International Consultation on Incontinence Questionnaire LUTS Quality of Life module (ICIQ-LUTSqol). A score > 5 on item 10b was considered indicative of a (major) problem. A total of 123 men with KIU, mean age 28 years (range: 18-50 years), completed the questionnaire(s): 81 (66%) completed IIEF-5, and 88 (72%) IIEF-15. Only 42% (N = 37) had been sexually active in the preceding four weeks. Mean IIEF-5 score in these patients was 18 (SD 5.7), with 63% meeting the criteria for ED. Mean IIEF-15 domain A score was 50 (SD 16.3), with 51% classified as having ED. Beyond ED, 39% reported reduced or absent ejaculation volume, and 52% reported mild to severe pain during ejaculation. Overall, 58-75% reported that LUTS had at least some negative impact on their sexual life, and 64% perceived this impact as a (major) problem. Less than half of men with KIU were sexually active in the past four weeks, with the majority reporting sexual health issues, including frequent erectile dysfunction and ejaculatory dysfunction, which were often perceived as significant problems. Awareness is needed among current and potential recreational ketamine users, as well as their healthcare providers, regarding the detrimental effects of ketamine not only on bladder function but also on sexual health.
Nut and seed press cakes are nutrient-rich by-products of oil extraction, traditionally directed to animal feed. This review synthesises current knowledge on the nutritional composition and functional properties of press cakes, with regards to their incorporation as sustainable protein and fibre rich ingredients in sports nutrition. A scoping review was conducted following PRISMA-ScR guidelines to identify studies on nut and seed press cakes relevant to sports nutrition. Nutrient composition and protein quality data were extracted from peer-reviewed sources, with comparisons made between whole nuts/seeds, press cakes, and comparable foods. As only three studies were eligible, the remainder of the review focussed on compositional factors and translation to sports nutrition contexts. Despite use of press cakes in agricultural contexts for animal feed, and some existing applications in human nutrition, no studies investigated their use for sport, recovery or performance. In comparison to whole nuts/seeds (mean protein content 19.3 g/100 g), protein content was higher in all but one press cake (35.4 g/100 g), with eight press cakes more than doubling the protein content of the whole food equivalent. Energy density was higher in two press cakes; total fat content was lower in all (51.1 g/100 g for whole, 14.3 g/100 g for press cakes). While none exceeded whey protein for leucine or lysine, seven press cakes exceeded WHO leucine guideline. Higher protein and fibre alongside lower energy density and total fat is aligned with some sport nutrition objectives. Together, there is academic and commercial precedent of press cakes being incorporated into food, especially as baked goods or in smoothies. Their nutritional profiles and compatibility with common foods support their translation to athletes, particularly those following plant-based or environmentally conscious diets, though more evidence is needed to solidify the efficacy of these proposed applications, particularly dose response.
Regular physical activity is a key determinant of psychological wellbeing, yet its interaction with emerging digital behavioral risks remains insufficiently understood. Compulsive internet use and nomophobia have been linked to psychological distress, which negatively affects life satisfaction and happiness. However, few studies have examined these factors simultaneously. Machine learning offers a promising approach for improving predictive accuracy and clarifying the relative contributions of these variables to subjective wellbeing. This study examined the combined predictive roles of physical activity, psychological distress, compulsive internet use, and nomophobia in subjective wellbeing (life satisfaction and happiness) and identified the optimal machine learning models for each outcome. A cross-sectional study was conducted among 1,479 community-dwelling adults (51.05% males) recruited between September and December 2024. Participants completed validated Arabic versions of the IPAQ-SF, DASS-21, CIUS, NMP-Q, SWLS, and SHS. Six machine learning algorithms (linear regression, random forests, support vector machines, XGBoost, k-nearest neighbors, and LASSO) were trained using an 80/20 train-test split with 5-fold cross-validation. Performance was evaluated using R 2, RMSE, and MAE. Psychological distress was the strongest negative predictor of wellbeing, showing the largest associations with happiness (r = -0.40) and life satisfaction (r = -0.37). Compulsive internet use was moderately associated with distress (r = 0.48), whereas nomophobia showed negligible relationships with both outcomes. For subjective happiness, random forest achieved the best performance (R 2 = 0.154, RMSE = 0.869), slightly outperforming linear regression and LASSO (R 2 = 0.153). For life satisfaction, linear regression and LASSO performed best (R 2 = 0.129, RMSE = 1.317), while support vector machines showed the lowest accuracy. Higher physical activity levels, particularly vigorous activity, were consistently associated with more favorable psychological profiles. Prediction of subjective wellbeing is outcome-specific, with different machine learning models performing optimally for happiness and life satisfaction. Psychological distress emerged as the strongest negative predictor, whereas physical activity demonstrated a consistent protective association. Longitudinal studies are needed to clarify causal pathways linking digital behavioral risks to wellbeing.
Trueperella pyogenes (T. pyogenes) is widely associated with suppurative infections in domestic animals and causes substantial economic losses to livestock production. With the increasing incidence of these infections and the growing prevalence of antimicrobial resistance, alternative therapeutic strategies against T. pyogenes are urgently needed. This study demonstrated that epigallocatechin gallate (EGCG), a natural product from green tea, exhibited antibacterial activity against T. pyogenes (MIC = 16-64 μg/mL; MBC = 32-64 μg/mL). At subinhibitory concentrations, EGCG inhibited bacterial growth, disrupted cellular integrity, and suppressed biofilm formation in T. pyogenes. In a mouse model, EGCG attenuated T. pyogenes infection, reduced the bacterial load in the spleen, and mitigated splenic tissue damage. Transcriptional analysis showed that EGCG at 1/2 MIC downregulated the mRNA expression of the plo gene, which encodes pyolysin (PLO), in T. pyogenes. Moreover, EGCG inhibited the hemolytic activity of T. pyogenes ATCC 19411. Molecular docking and molecular dynamics simulations further indicated a stable interaction between EGCG and PLO. Our data demonstrate the efficacy of EGCG as a potential agent in combating T. pyogenes infections and provide preliminary insight into the potential mechanism for its inhibitory effect on PLO.
Hepatocellular carcinoma (HCC) is a lethal liver malignancy associated with substantial morbidity and mortality and remains a major socioeconomic burden worldwide. Given the high risk associated with HCC, novel therapeutic approaches are urgently needed. Angelica sinensis is a traditional Chinese herbal remedy that contains bioactive phytochemicals with promising anticancer properties, making it a potential candidate for evaluation in HCC. This study integrated computational network pharmacology, molecular docking, and in vitro cellular assays to elucidate the mechanisms by which A. sinensis exerts anti-HCC effects in Hep-G2 cells. Phytochemicals were identified using the Traditional Chinese Medicine Systems Pharmacology database and filtered according to drug-likeness and oral bioavailability criteria. Key compounds (β-sitosterol, alpha-cephalin, sitogluside, and stigmasterol) were further analyzed using the SuperPred Target Prediction tool to predict potential targets. HCC-related targets were curated from GeneCards and refined using the GeneCards Inferred Functionality Score. The overlap between compound-related and disease-specific targets was used to construct a protein-protein interaction network using STRING, which was subsequently visualized in Cytoscape to identify hub genes. Molecular docking between stigmasterol and the top 3 hub genes was evaluated using the CB-Dock2 online server, and all preparations were performed in BIOVIA Discovery Studio. In vitro, Hep-G2 cells were treated with varying concentrations (0, 25, 50, 100, and 200 µg/mL) of A. sinensis extract. Cell viability, clonogenic potential, apoptosis induction, and migratory capacity were evaluated using the MTT assay, clonogenic assay, Annexin V/PI staining, and Transwell migration assay, respectively. Western blotting was used to assess the expression of key hub proteins in Hep-G2 cells. In silico analysis identified an initial pool of 126 phytochemicals, which was refined to 4 key compounds yielding 139 unique targets. Intersection with HCC-related targets produced 123 common targets, generating a network comprising 119 nodes and 520 edges. STAT3, NFKB1, and TLR4 were identified as pivotal hub genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the hub genes demonstrated significant enrichment in HCC-related pathways and biological processes. Molecular docking indicated a strong binding affinity of stigmasterol to STAT3, NFKB1, and TLR4, with binding energies of -7.8, -6.9, and -6.9 kcal/mol, respectively. In vitro assays showed a dose-dependent reduction in Hep-G2 cell viability and colony formation, significant induction of apoptosis, and marked inhibition of migration. Western blotting confirmed significant downregulation of STAT3, NFKB1, and TLR4 expression at higher extract concentrations. This study concluded that A. sinensis herbal extract was predicted to exert potent antiproliferative effects against HCC through the possible modulation of key signaling pathways and the targeting of hub genes, supporting its potential for further therapeutic development.
Rapid warming in the Gulf of Maine and shifts in bait usage in Maine's lobster industry are altering the thermal and nutritional landscapes for American lobsters (Homarus americanus), with unknown sublethal impacts on lobster physiology. Specific dynamic action (SDA) is the postprandial rise in metabolism that comprises the energy needed to digest and assimilate a meal. SDA may influence lobsters' survival by occupying a portion of their aerobic scope, thus limiting their capacity to deal with environmental stressors. Here, we used intermittent-flow respirometry to investigate the combined impacts of acclimation temperature (15 or 18°C) and the consumption of a bait item [frozen menhaden (Brevoortia tyrannus), fresh mussel (Mytilus edulis), or salted pig hide (Sus domesticus)] on aerobic metabolism and SDA in adult male lobsters. While standard metabolic rate and peak SDA were not significantly impacted by temperature, SDA duration was, indicating thermal plasticity and resilience to present and near-future oceanic conditions. Postprandial residual aerobic scope was not significantly impacted by bait item, suggesting tolerance of short-term nutritional variation. Lobsters fed pig hide demonstrated the greatest peak SDA, likely due to its higher caloric content and an artificially reduced need for mechanical digestion of menhaden and mussel hard parts. Our findings demonstrate that while metabolic function appears robust to moderate warming and altered nutrition in isolation, temperature-diet interactions can constrain maximum aerobic capacity with potential implications for postcapture survival and bait regulation.
Contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is rare in children, and available clinical data are limited. Our aim is to describe the clinical spectrum, diagnostic findings, treatment, and outcomes of all pediatric CASPR2 antibody-associated encephalitis patients reported in Hungary. We present a retrospective case series including nine pediatric patients diagnosed with CASPR2 antibody-associated encephalitis across five centers. Clinical, laboratory, imaging, electrophysiological findings, treatment, and follow-up data were collected. The mean age at onset was 4.1 ± 2.6 years. All patients were serum CASPR2 antibody-positive; two had CSF positivity. The most common symptoms included sleep disorder, irritability, aggressiveness, hypertension, tachycardia, abdominal pain, itching, exanthema, and weight loss. No specific abnormalities were detected on MRI, EEG, or laboratory testing. Immunotherapy led to favorable outcomes in nearly all patients, with one relapse during follow-up. This series expands the clinical spectrum of CASPR2-associated autoimmune encephalitis in children. The presenting symptoms in pediatric patients may differ not only from those observed in adults but also from other forms of autoimmune encephalitis. The diagnostic process is especially complex due to the variability and age-related evolution of clinical manifestations, which can be difficult to recognize in younger children and commonly contribute to diagnostic delay. Early recognition and immunotherapy are associated with favorable prognosis. This case series underscores the importance of recognizing the diverse spectrum of presenting symptoms and highlights the need for raising awareness of the clinical variability. Larger prospective studies are needed to define diagnostic, therapeutic strategies and prognostic factors in the pediatric population.
Interventions are urgently needed for young people waiting for Child and Adolescent Mental Health Services (CAMHS) in England. Long waits can worsen mental health, increase distress for young people and families, and place additional pressure on already stretched services. Social prescribing, a referral system for connecting individuals with resources in the community via one-to-one support from a link worker, has not been routinely implemented or evaluated for young people on CAMHS waitlists. It remains unclear whether, and under what conditions, social prescribing can be implemented successfully within CAMHS. We conducted semi-structured interviews with 23 staff and link workers involved in implementing social prescribing at 11 CAMHS sites across England as part of a large hybrid type II implementation-effectiveness study. We used a framework analysis approach, deriving the coding from the updated Consolidated Framework for Implementation Research (CFIR). Barriers and facilitators mapped to 12 CFIR constructs, generating 25 themes. Key areas included: the challenges of implementing a non-medical intervention in a clinical environment; the advantage of social prescribing compared to little waitlist support; the need for flexibility in mode, duration, and frequency of sessions; the importance of community assets, funding and external partnerships for delivery; and the capacity, skills, and professional experience of link workers and staff. Barriers within CAMHS related to limited resources and partial understanding of the intervention, as well as difficulties in integrating link workers and providing supervision. Successful implementation depended on tailoring the intervention to the needs and preferences of young people and parents. Alternative social prescribing pathways were proposed, with schools being recommended as a promising setting for preventive delivery or post-treatment transitions for young people. Youth social prescribing for young people on CAMHS waitlists is feasible but requires careful implementation. Successful delivery depends on the capacity of link workers and supportive organisational structures in CAMHS. Alternative pathways, including delivery outside the waitlist through schools may facilitate its implementation and impact.
Tonic motor activation (TOMAC) delivers high-frequency electrical stimulation to the common peroneal nerve to reduce restless legs syndrome symptoms and improve subjective sleep quality. This cross-sectional analysis provides the first objective evaluation of the wake-sleep transition and an exploration of sleep parameter and leg movement changes following mid-sleep TOMAC sessions during polysomnography. Twenty participants with medication-refractory restless legs syndrome completed two polysomnographies and activated 30-min TOMAC sessions as needed when awakening mid-sleep with restless legs syndrome symptoms. Objective sleep parameters including sleep reinitiation latency, architecture, and hourly indices of periodic leg movements during sleep (PLMS) and PLMS associated with arousal were compared between the sleep periods before and after activating mid-sleep TOMAC sessions. Sleep reinitiation occurred during the 30-min TOMAC session for 24 of 29 (82.8%) mid-sleep sessions, with a median latency of 6.7 (range = 0.9-45.9) min following TOMAC activation. The latency from TOMAC activation to sleep reinitiation was shorter in participants who activated TOMAC within 10 min of awakening compared to those who waited longer (p = 0.016). There was a linear increase in the proportion of delta and a decrease in alpha electroencephalogram (EEG) frequency-band power after activating mid-sleep TOMAC (both p < 0.001), indicating the transition towards deeper sleep. Comparing sleep intervals before and after activating mid-sleep TOMAC, PLMS/hour decreased by 47.9% (p = 0.042) and PLMS associated with arousal/hour decreased by 70.8% (p = 0.004). TOMAC was compatible with sleep; rapid sleep reinitiation and a transition to deeper sleep were observed during TOMAC stimulation. These data also provide proof-of-concept evidence that PLMS may decrease following activation of mid-sleep TOMAC. This study was preregistered on January 31, 2022 ClinicalTrials.gov with name "Noninvasive Peripheral Nerve Stimulation for Medication-Naive and Medication-Refractory RLS" and number NCT05214963 at https://clinicaltrials.gov/study/NCT05214963.
Chronic low back pain (CLBP) is a major global health challenge. While nonpharmacological therapies are recommended, patient compliance is often hindered by kinesiophobia. Virtual reality (VR) offers an immersive, distraction-based approach, but the comparative effectiveness of different VR modalities remains unclear. The aim of the study is to compare and rank the efficacy of different VR-based training modalities on pain intensity, disability, and kinesiophobia in patients with CLBP. Systematic searches were conducted in PubMed, Web of Science, Scopus, Embase, CINAHL, and the Cochrane Library from inception until June 2025. Randomized controlled trials (RCTs) assessing the effects of VR-based training on individuals with CLBP were selected. Primary outcomes were pain intensity, disability (Oswestry Disability Index), and kinesiophobia (Tampa Scale of Kinesiophobia). The Cochrane Risk of Bias 2 tool was used for quality assessment. Confidence in Network Meta-Analysis (CINeMA) framework was used to evaluate the credibility of cumulative evidence. A Bayesian network meta-analysis with standardized mean difference (SMD) as effect size was performed to synthesize evidence and rank interventions using surface under the cumulative ranking curve values. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework was adapted to evaluate the quality of evidence. In total, 25 RCTs with a total of 2610 participants were included in the analysis. For pain intensity, shooting games (SMD -4.40, 95% credible interval [CrI] -6.80 to -2.20) and VR-based equestrian training (SMD -2.00, 95% CrI -3.70 to -0.57) were significantly superior to all types of controls. Surface under the cumulative ranking curve indicated that shooting games had the highest probability (98%) of being the most effective intervention for pain relief. For disability, no intervention demonstrated statistically significant superiority. For kinesiophobia, shooting games (SMD -3.40, 95% CrI -5.60 to -1.10) significantly outperformed traditional exercise controls. The quality of evidence ranged from very low to moderate across outcomes. This first network meta-analysis to compare and rank distinct VR modalities for CLBP offers several key innovations and contributions to the field. By moving beyond aggregate VR categorizations, we provide a granular, comparative ranking of specific, actionable VR interventions. Unlike previous reviews that treated VR as a homogeneous group or only compared it to sham, our network meta-analysis directly and indirectly compares 7 distinct VR modalities, revealing that not all VR is equally effective. Our findings suggest that shooting games have the potential to be the most effective VR therapy for relieving pain intensity and kinesiophobia, though evidence for disability remains limited. Unfortunately, due to heterogeneity and low-quality evidence, there is no evidence demonstrating significant improvement in specific outcomes for patients with CLBP. More RCTs are needed to provide robust clinical evidence.
Advanced Therapy Medicinal Products - cell therapies, gene therapies, and tissue-engineered products - are beginning to deliver on the promise of curative medicine: CAR-T therapies double survival in chemotherapy-refractory lymphomas, gene therapies reverse the natural history of spinal muscular atrophy and hemoglobinopathies, and Pluripotent Stem Cell (PSC)-derived islet transplantation renders type 1 diabetic patients insulin-independent. Yet the trajectory from proof-of-concept to equitable, scalable deployment is consistently impeded not only by unresolved biology but also by engineering, manufacturing, logistical, regulatory, and economic bottlenecks that the bioengineering community has not engaged with at the required scale. In this Perspective, grounded in clinical experience across hematological malignancies, monogenic diseases, and metabolic disorders, we identify five rate-limiting bottlenecks where bioengineering intervention is urgently needed and uniquely tractable: scalable and adaptive biomanufacturing; real-time in-process quality control; precise targeted delivery; biomaterial and scaffold engineering for cellular engraftment and immune protection; and data-driven patient stratification constrained by health equity. We argue that the evolving regulatory landscape in Europe - including the European Biotech Act framework and ICH Quality by Design principles - creates structural incentives for engineering-led solutions, and that economic sustainability requires bioengineering to drive down production costs and enable the off-the-shelf transition. We call on the bioengineering community to engage with ATMP translation not as technical support to clinical medicine, but as a constitutive partner shaping its pace, cost, and equity.
Noncontact anterior cruciate ligament (ACL) injuries are common and carry long-term consequences for the athlete. Altered foot and ankle biomechanics, landing patterns, and prior ankle injury have been implicated in ACL injury risk and may inform prevention strategies. To identify key biomechanical risk factors associated with the foot and ankle that may contribute to ACL injury risk. Systematic review; Level of evidence, 4. A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. PubMed, Cochrane, and SPORTDiscus databases were searched for English-language studies (2010-2025) evaluating ACL injuries and reporting on the foot or ankle. Screening was performed using Rayyan, followed by full-text review. Data were extracted, and then risk of bias was assessed using the methodological index for non-randomized studies (MINORS). Out of 1772 studies evaluated, a total of 48 (2.7%) studies met inclusion criteria. Overall, 33 studies (68.8%) identified variables associated with increased ACL injury risk, while 11 (22.9%) reported decreased risk and 9 (18.8%) found no association. Foot and ankle biomechanics were examined in 32 studies (66.7%), foot strike pattern in 8 (16.7%), toe direction in 7 (14.6%), and prior ankle injury history in 5 (10.4%). Statistically supported findings were present in 81% of studies. Greater dynamic rearfoot motion (eversion/inversion), increased dorsiflexion, and medial arch collapse (eg, navicular drop) were commonly associated with increased risk. Forefoot landings were protective, while rearfoot and flatfoot strikes, as well as toe-in or toe-out positions, were consistently linked to higher injury risk. Sex-specific analysis showed that female athletes demonstrated more high-risk biomechanical patterns than their male counterparts. Sport-specific analysis revealed basketball (n = 14), soccer (n = 8), and handball (n = 6) as the most studied sports, with >75% of these studies identifying ≥1 foot- or ankle-related ACL injury risk factor. Study quality was generally low, with predominantly noncomparative designs and modest MINORS. Foot and ankle factors, including prior injury, alignment, foot strike patterns, and toe progression, contribute meaningfully to ACL injury risk, yet their precise influence on knee stabilization remains unclear. The foot and ankle are understudied, with few investigations addressing their role in dynamic tasks that challenge knee stability. High-quality comparative research that accounts for sex and sport differences is needed to inform targeted prevention and improve risk stratification.
Viral hepatitis is a major cause of chronic liver disease, including cirrhosis and hepatocellular carcinoma, with significant morbidity and mortality. Individuals with sickle cell disease (SCD) are at increased risk of hepatitis C virus (HCV) infection due to frequent transfusions. Despite the high burden of HCV in Uganda, recent data on HCV seroprevalence among individuals with SCD are limited. To determine HCV seroprevalence and describe characteristics among patients with SCD receiving care at Mulago National Referral Hospital (MNRH), Kampala, Uganda. Hospital-based cross-sectional study. Individuals with SCD attending the MNRH outpatient SCD clinic in Kampala, Uganda, were recruited between July and September 2025. Sociodemographic, clinical, and behavioral data were collected using a structured questionnaire. Anthropometric measurements were taken using standardized scales. HCV, hepatitis B surface antigen (HBsAg), and HIV rapid tests were performed. Data were analyzed using the SAS statistical package version 9.4. There were 119 participants with SCD enrolled, with a mean age of 13.1 years, and 55.5% (n = 66) were male. Most participants had a SCD diagnosis for 6 years or longer. HCV seroprevalence was 12.6% (n = 15). All HCV-seropositive participants were less than 18 years, with nearly two-thirds of those aged 9-17 years (66.7%, n = 10). Nearly all HCV-seropositive participants had a history of blood transfusion (n = 14, 93.3%), with 53.3% (n = 8) reporting three or more transfusions. Only one participant (0.84%) tested positive for HIV, and none tested positive for HBsAg. This study revealed a high seroprevalence of HCV among individuals with SCD in Uganda. Strengthening routine HCV screening, linkage to care, and infection prevention, including within blood transfusion services, is needed. Larger studies incorporating HCV RNA testing are recommended to assess the true burden of active infection and risk factors among patients with SCD to inform targeted prevention, screening, and treatment strategies. Hepatitis C infection among people with sickle cell disease at Mulago National Referral Hospital, Uganda Hepatitis C virus (HCV) infection is a viral infection that can cause long-term liver disease if not detected and treated early. People living with sickle cell disease (SCD) are at an increased risk of HCV infection due to multiple risk factors, such as multiple blood transfusions and other exposures, such as sharing contaminated medical equipment. In this study, we aimed to determine the seroprevalence of HCV and describe characteristics among patients with SCD receiving care at Mulago National Referral Hospital, Kampala, Uganda. We tested 119 people with SCD using a rapid HCV antibody test and found that 12.6% of participants tested positive, indicating prior exposure to HCV. All individuals who tested positive were younger than 18 years, and most had received blood transfusions in the past. These findings highlight the importance of routine HCV screening in routine SCD care. Larger studies that include confirmatory testing for active ongoing infection are recommended to guide targeted prevention, screening, and treatment efforts.
Stroke is a leading cause of disability and mortality in older adults. Post-stroke cognitive frailty (CF) increases the risk of adverse outcomes. However, evidence regarding the prevalence of CF remains limited and inconsistent. This study aims to systematically evaluate the prevalence of CF among older adults with stroke in China and identifies factors associated with variation in prevalence, thereby informing future research directions and potential clinical considerations. We searched PubMed, Embase, Web of Science, Cochrane Library, China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP Database, and Wanfang Database for relevant studies reporting the prevalence of CF in Chinese older adults with stroke. The search covered the period from each database's inception to November 2024. Eligible studies were assessed for quality, and data were extracted. All analyses were performed using Stata 18.0 software. Four Chinese studies involving 1,337 participants were included. Meta-analysis revealed a pooled prevalence of CF among older adults with stroke of 33% (95% CI: 28-39%). Subgroup analysis indicated a significantly higher prevalence of CF in stroke patients aged ≥80 years compared to those aged 60-79 years (p < 0.05). Furthermore, the prevalence was significantly higher among those who consumed alcohol than among non-consumers (p < 0.05). Notably, subgroup estimates for patients with malnutrition and depression were markedly high, at 47% (95% CI: 34-60%) and 62% (95% CI: 53-71%), respectively. Available evidence suggests that the prevalence of CF among older adults with stroke in China appears to be substantial, with significant variations associated with alcohol consumption and advanced age. The particularly high prevalence estimates in patients with malnutrition or depression warrant increased clinical attention and further investigation into their relationship with post-stroke CF. Caution is warranted given the limited evidence base (n = 4), high heterogeneity, and exclusively hospital-based Chinese setting; larger studies are needed to confirm these observations. Early identification and evidence-based interventions targeting CF in this population may be crucial to mitigating adverse health outcomes pending further validation. This systematic review was prospectively registered with PROSPERO (registration number: CRD42025643159).
Postoperative depressive symptoms may impair recovery and quality of life in patients undergoing breast cancer surgery. Esketamine has shown potential antidepressant and analgesic effects in the perioperative setting. This meta-analysis evaluated the efficacy and safety of perioperative esketamine for postoperative depressive symptoms in patients undergoing breast cancer surgery. PubMed, Embase, Cochrane Library, Web of Science, CNKI, and WanFang were systematically searched from database inception to 18 May 2026. Randomized controlled trials comparing perioperative esketamine with control interventions in patients undergoing breast cancer surgery were included. The primary outcome was postoperative depressive symptom score. Secondary outcomes included postoperative pain scores and adverse events. Random-effects models were used as the primary analytical approach. Risk of bias and certainty of evidence were assessed using the RoB 2 tool and the GRADE approach, respectively. Fifteen randomized controlled trials involving 1,515 patients were included. Perioperative esketamine was associated with significantly lower postoperative depressive symptom scores at postoperative day 1 (SMD = -0.78, 95% CI: -1.08 to -0.48), postoperative day 3 or 48-72 h (SMD = -1.07, 95% CI: -1.63 to -0.51), postoperative day 7 (SMD = -0.79, 95% CI: -1.10 to -0.49), and long-term follow-up (SMD = -1.16, 95% CI: -1.68 to -0.64). For postoperative pain, esketamine was associated with lower postoperative pain scores at postoperative day 1 or 24 h (MD = -0.66, 95% CI: -1.11 to -0.21) and postoperative day 3 or 48-72 h (MD = -0.66, 95% CI: -1.09 to -0.23), but not at postoperative day 7. However, substantial heterogeneity and wide prediction intervals were observed for pain outcomes. The incidences of nausea and vomiting, postoperative delirium, and dizziness did not differ significantly between the esketamine and control groups. The certainty of evidence ranged from low to very low across outcomes. Perioperative esketamine may reduce postoperative depressive symptom scores and provide short-term analgesic benefits in patients undergoing breast cancer surgery. However, substantial heterogeneity, methodological limitations, and low to very low certainty of evidence warrant cautious interpretation. Further high-quality randomized trials are needed. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251173178, identifier CRD420251173178.
Parathyroid hormone (PTH) influences calcium handling in cardiomyocytes and sympathetic cardiac signaling. It has been linked to arterial hypertension and cardiovascular mortality. We hypothesized that PTH is independently associated with atrial fibrillation (AF). We analyzed data from 3,201 patients (mean age 63 ± 13 years, 25.8% female) enrolled in the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. We defined AF based on medical history or current ECG. Multivariable binary logistic regression was used to assess the association between PTH and AF, adjusting for established AF risk factors, parameters of mineral metabolism, kidney function, and concomitant medication. AF was present in 389 patients (12.2%). PTH was significantly associated with AF in the primary multivariable model [OR 3.96 (2.32-6.76), p < 0.001]. In the fully adjusted model including mineral metabolism and medication variables, the association remained significant [OR 2.32 (1.24-4.35), p = 0.009]. The association remained significant after additional adjustment for markers of cardiac dysfunction, including invasive hemodynamic parameters. Elevated PTH was associated with prevalent AF in patients referred for coronary angiography after adjustment for common confounders. The association persisted after adjustment for structural, neurohumoral and invasive hemodynamic markers, suggesting that elevated PTH is not merely a surrogate of cardiac dysfunction but may represent an independent correlate of AF. Prospective studies are needed to clarify the temporal and causal relationship between PTH and AF.
We aimed to determine the effects of a 12-month antimicrobial stewardship (AMS) programme in two provincial-level general hospitals in Viet Nam, a lower-middle-income country. We performed controlled interrupted time-series analyses to evaluate the intervention effects on antibiotic use in days of therapy (DOT) per 1000 patient-days, antibiotic non-susceptibility percentage and patient outcomes. In each hospital, four wards received the intervention, and four wards acted as controls. Pre-intervention periods began in January 2019 and continued to May 2020 (Hospital 1) and July 2020 (Hospital 2). Regarding antibiotic use, the intervention was associated with an immediate absolute reduction of 95.9 DOT/1000 patient-days (95%CI 10.9-180.8) in Hospital 1, while Hospital 2 showed no overall change but declining slopes in selected antibiotics including aminoglycosides and penicillin/beta-lactamase inhibitors. Escherichia coli showed decreasing non-susceptibility to aminoglycosides and third-generation cephalosporins in both hospitals. Carbapenem non-susceptibility increased for both E. coli and Klebsiella spp. in Hospital 2 but decreased for Klebsiella spp. in Hospital 1. Non-susceptibility of P. aeruginosa increased to carbapenems (Hospital 1), aminoglycosides, ciprofloxacin and ceftazidime (Hospital 2). Acinetobacter spp. showed increased non-susceptibility to aminoglycosides and piperacillin-tazobactam in Hospital 1 but decreased to carbapenems, ciprofloxacin and piperacillin-tazobactam in Hospital 2. No evidence of changes in mortality or hospitalization costs were observed in both hospitals. The impact of AMS varied between the two hospitals, highlighting the context-specific nature of implementation. Sustained monitoring of antibiotic use and resistance is needed to support locally tailored interventions that respond to evolving resistance epidemiology.
The rapid advancement of Artificial Intelligence (AI) in medical education is driving a shift from traditional instructional design methods toward personalized and adaptive learning models. Despite numerous promising applications, the available evidence remains limited and fragmented; therefore, a comprehensive synthesis of the evidence is needed to support robust conclusions. This study employed the four-phase meta-synthesis framework proposed by Sandelowski and Barroso. A systematic search was conducted across Medline, Embase, CINAHL, PsycINFO, PubMed, Web of Science, ScienceDirect, Wiley Online Library, SpringerLink, Taylor & Francis Online, SAGE Journals, and Scopus, covering publications from 2010 to 2025. Studies were screened according to predefined inclusion and exclusion criteria, and their methodological quality was evaluated using the Critical Appraisal Skills Programme (CASP). Coding reliability was assessed through a test-retest procedure, resulting in a reliability coefficient of 0.81. A total of 273 records were identified, of which 16 studies met the inclusion criteria and obtained CASP scores exceeding the threshold of 30. Content analysis revealed five principal domains: faculty-related applications (21%), student-related applications (28%), applications in the learning process (15%), curriculum development (13%), and assessment mechanisms (23%). Student-related applications constituted the largest proportion, highlighting the pivotal role of learner-centered personalization in AI-driven medical education. The integration of Artificial Intelligence (AI) into individualized educational experiences represents a transformative model for medical education. AI enables adaptive learning pathways, dynamic assessment methods, and data-driven instructional environments, thereby enhancing student engagement, fostering faculty innovation, and promoting equity in learning outcomes. This synthesis proposes an overarching conceptual framework to inform policy, research, and implementation in the context of AI-supported personalized medical education.