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Mitophagy-mediated ferroptosis involved in 2,5-hexanedione-induced neurotoxicity in rats.

n-Hexane, a widespread environmental and industrial pollutant, poses serious health risks, particularly neurotoxicity. Chronic exposure primarily induces sensorimotor neuropathy via its metabolite 2,5-hexanedione (HD), yet the mechanisms underlying HD-induced neuronal injury remain unclear. Recent evidence implicates ferroptosis, an iron-dependent form of regulated cell death, in neurodegenerative processes. In this study, Sprague-Dawley (SD) rats were exposed to HD to establish a neuropathy model. Ferroptosis involvement was assessed using the iron chelator deferoxamine (DFO) and the ferroptosis inhibitor Ferrostatin-1. The potential role of mitophagy in HD-induced ferroptosis was evaluated by monitoring mitophagy markers and by autophagy inhibition with chloroquine (CQ). In vitro, SH-SY5Y cells were transfected with PINK-1 siRNA to explore mitophagy-mediated regulation of ferroptosis. HD exposure led to iron accumulation, lipid peroxidation, mitochondrial abnormalities, and decreased GPX4 in rat spinal neurons. DFO or ferrostatin-1 treatment ameliorated these changes and preserved mitochondrial integrity. Mechanistic analyses revealed HD-induced activation of mitophagy, as shown by upregulation of Beclin-1, LC3II, Drp-1, and PINK-1, with concomitant downregulation of P62 in spinal mitochondria. CQ suppressed mitophagy, reduced iron deposition and lipid peroxidation, and improved motor function. Similarly, PINK-1 knockdown in SH-SY5Y cells mitigated HD-induced mitophagy and ferroptosis. These findings demonstrate that HD induces neuronal ferroptosis via mitophagy activation. Inhibition of ferroptosis or mitophagy effectively attenuates HD-induced neurotoxicity, suggesting potential therapeutic strategies to reduce neural damage from environmental n-hexane exposure.

Animals

Acute pre-exercise oral intake of cacao polyphenols attenuates central fatigue development during sustained low-intensity ankle dorsiflexion exercise in healthy young male adults.

This double-blind, randomized, crossover study investigated whether acute cacao polyphenol (CP) ingestion attenuates neuromuscular fatigue in 19 healthy young male adults. After consuming CP or placebo, participants performed sustained isometric ankle dorsiflexion at 25% of maximal voluntary isometric contraction (MVIC) torque until task failure. Neuromuscular function (MVIC torque, voluntary activation [VA%], doublet torque) and electromyographic activity were assessed before, immediately after, and during recovery (1 and 5&#x2009;min). Salivary chromogranin A and &#x3b1;-amylase were measured at baseline and 1&#x2009;min post-task. Only VA% and chromogranin A showed significant condition &#xd7; time interactions (p&#x2009;=&#x2009;0.027-0.039). VA% significantly decreased from before to immediately after the task and 1&#x2009;min post-task in both conditions (p&#x2009;&#x2264;&#x2009;0.002), with significantly higher values in the CP condition than in placebo immediately after and 1&#x2009;min post-task (p&#x2009;&#x2264;&#x2009;0.037). Chromogranin A significantly increased from baseline to 1&#x2009;min post-task in the placebo condition (p&#x2009;<&#x2009;0.001) but not in the CP condition (p&#x2009;=&#x2009;0.083). These findings suggest that acute CP ingestion attenuates the decline in central motor drive and autonomic stress responses following strenuous exercise, without altering performance or peripheral recovery, supporting its potential as a nutritional strategy for modulating central fatigue.

Humans

Low-salinity stress alters growth, histology, physiology, and transcriptomic profiles of the gills and antennal glands in Macrobrachium rosenbergii.

Salinity is a major abiotic constraint in freshwater aquaculture of the giant freshwater prawn Macrobrachium rosenbergii, yet the coordinated roles of the gills and antennal glands, the two primary osmoregulatory organs in decapod crustaceans, under low-salinity stress remain poorly characterized. Here, we integrated histological, physiological, and transcriptomic analyses to characterize the adaptive responses of M. rosenbergii to acute (96&#xa0;h) and chronic (8&#xa0;weeks) exposure to salinity 5. Chronic low-salinity stress significantly impaired growth performance and decreased the survival rate. Acute stress induced thinning of the gill filaments, partial disorganization of pillar cells, and dilation of the intermicrovillar space in the antennal glands, whereas chronic stress caused gill vacuolization, cuticle thinning, and adaptive folding of antennal gland microvilli. In parallel, acute exposure significantly decreased hemolymph sodium and potassium ion concentrations but increased magnesium ion concentration, whereas chronic exposure increased hemolymph sodium and potassium ion concentrations, upregulated gill Na+/K+-ATPase activity, and enhanced hepatopancreatic antioxidant capacity. Transcriptomic analyses revealed distinct tissue-specific responses. Under acute stress, the gills preferentially activated pathways associated with cytoskeletal remodeling, motor proteins, and tight junctions, whereas chronic acclimation shifted the transcriptional response toward the renin-angiotensin system and glutathione metabolism. In the antennal glands, acute stress rapidly activated the renin secretion pathway, whereas chronic exposure promoted membrane remodeling by enriching pathways related to lipid and glycan metabolism. These findings reveal tissue-specific functional differentiation and synergistic coordination between the gills and antennal glands that underpin M. rosenbergii's adaptive response to low-salinity stress.

Animals

Blue light therapy delivered through light glasses improves sleep quality and daytime sleepiness in Parkinson's disease: A randomized trial.

BackgroundSleep disturbances, including excessive daytime sleepiness (EDS) and fragmented nocturnal sleep, are common in Parkinson's disease (PD) and significantly reduce quality of life. This pilot study evaluated the efficacy of a novel approach using blue light, delivered via dedicated glasses with integrated LED lights, to improve sleep and non-motor symptoms.MethodsRandomised, placebo-controlled, single-blind pilot study with a 2-week light intervention. Participants were assessed at baseline, two weeks, and five weeks. The study was designed to evaluate between- and within-group changes. Participants were randomly allocated to receive blue light therapy (n&#x2009;=&#x2009;15) or red light placebo (n&#x2009;=&#x2009;15), delivered via LED-integrated glasses for one hour, twice daily, given for a 2-week period. Primary outcome was improvement in sleep quality, assessed via the Pittsburgh Sleep Quality Index. Secondary outcomes included diary-based sleep outcomes, excessive daytime sleepiness, mood, anxiety, and motor symptoms.ResultsThere was a significant group&#x2009;&#xd7;&#x2009;time effect with blue light therapy leading to better Pittsburgh Sleep Quality Index scores (p&#x2009;=&#x2009;0.021). Between-group analyses showed that at two weeks a trend toward significance was observed (p&#x2009;=&#x2009;0.065), while sleep quality significantly improved at five weeks compared to placebo (p&#x2009;=&#x2009;0.029) with a large effect size (0.896). Excessive sleepiness improved in the blue light group (p&#x2009;<&#x2009;0.001), with a reduction in clinically relevant sleepiness from 50.0% to 6.7% (p&#x2009;=&#x2009;0.005).ConclusionsBlue light therapy delivered through dedicated glasses appeared to show an improvement in sleep quality and daytime sleepiness in individuals with PD. Blue light therapy offers a promising alternative to traditional light therapy utilising lower light intensities and eliminating the need for light boxes.

Aged

Extended Venous Thromboembolism Prophylaxis After One-Anastomosis Gastric Bypass: A Three-Arm Randomized Trial of Enoxaparin Duration and Rivaroxaban.

BACKGROUND: Venous thromboembolism (VTE) is a serious but preventable complication after bariatric surgery, most of them after hospital discharge. The optimal regimen and duration of post-discharge prophylaxis, particularly the role of direct oral anticoagulants, remain uncertain. OBJECTIVES: To estimate 30-day VTE and bleeding event rates in high-risk patients undergoing one-anastomosis gastric bypass who received 15-day enoxaparin, 30-day enoxaparin, or 30-day rivaroxaban prophylaxis, and to perform exploratory comparisons among the regimens. METHODS: In this randomized, open-label, three-arm clinical trial, high-risk adults undergoing laparoscopic OAGB were randomized before discharge (1:1:1) to enoxaparin 40&#xa0;mg subcutaneously twice daily for 15 days, enoxaparin 40&#xa0;mg twice daily for 30 days, or rivaroxaban 10&#xa0;mg orally once daily for 30 days, after standardized in-hospital enoxaparin and early ambulation. Participants underwent clinical assessment and duplex ultrasonography of the lower-limb and porto-mesenteric veins on postoperative days 15 and 30. The primary outcome was objectively confirmed VTE within 30 days. Bleeding was classified as International Society on Thrombosis and Haemostasis (ISTH) major bleeding or clinically relevant non-major bleeding (CRNMB). Because the expected event rate was low and no non-inferiority or equivalence margin was prespecified, comparisons were interpreted as exploratory. RESULTS: A total of 288 patients were randomized to 15-day enoxaparin (n&#x2009;=&#x2009;97), 30-day enoxaparin (n&#x2009;=&#x2009;97), or 30-day rivaroxaban (n&#x2009;=&#x2009;94). One symptomatic lower-limb deep vein thrombosis occurred in the 15-day enoxaparin group (1.0%; 95% CI, 0.03%-5.6%); no VTE events occurred in the 30-day enoxaparin group (0%; 95% CI, 0%-3.7%) or the rivaroxaban group (0%; 95% CI, 0%-3.8%). Total bleeding occurred in 4/97 patients (4.1%) in each enoxaparin group and 8/94 patients (8.5%) in the rivaroxaban group. The absolute difference in total bleeding between rivaroxaban and 30-day enoxaparin was 4.4% points (95% CI, -&#x2009;2.9 to 12.2), indicating substantial imprecision. No porto-mesenteric venous thrombosis was detected. CONCLUSION: Only one VTE event occurred, precluding reliable conclusions regarding comparative efficacy or prophylaxis duration. Bleeding estimates were also imprecise and do not establish comparative safety or equivalence between rivaroxaban and enoxaparin. The trial adds descriptive event-rate data from a standardized OAGB pathway, but larger multicenter studies with prespecified comparative hypotheses and assessment of adherence, oral tolerance, and drug exposure are required. The study was approved by the Research Ethics Committee and registered at ClinicalTrials.gov.

Humans

Low-burden metrics for monitoring healthy diets among nonpregnant females aged 15 to 49 years: a multicountry validation analysis using quantitative 24-hour dietary intake data.

BACKGROUND: Limited nationally representative quantitative dietary intake data and a lack of consensus on lower-burden tools and metrics hinder high-frequency monitoring of healthy diets globally. OBJECTIVES: This study aimed to evaluate the comparative construct validity and potential complementarity of low-burden metrics of a healthy diet among nonpregnant females aged 15 to 49 y. METHODS: Quantitative 24-h dietary intake data collected from 77,118 adolescent and adult females across 27 countries were used to construct low-burden metrics and reference metrics of dietary intake. Associations between mean-standardized low-burden measures or indicators and reference metrics were assessed using linear and logistic mixed-effect models, with Spearman's &#x3c1; used for survey-level rank correlations. Test characteristics identified low-burden indicators best differentiated adherence to reference indicators. RESULTS: An indicator reflecting nonconsumption of sweet foods and/or sweet beverages was most robustly associated with greater adherence to <10% energy from free sugars in upper-middle-income countries {odds ratio [OR] [95% confidence interval (CI)]: 5.35 [5.05, 5.66]}. Food group diversity score (FGDS) was most strongly associated with and differentiated higher mean adequacy ratio of micronutrients [&#x3b2; of 1-standard deviation (SD) change: &#x223c;11 percentage points (9, 12); &#x3c1;: 0.79], whereas noncommunicable disease-Protect score best reflected consumption of &#x2265;400 g/d of fruits and vegetables [range OR of 1-SD changes (95% CI): 2.56-3.01 (2.40, 3.13) in lower-middle and high-income countries, respectively; &#x3c1;: 0.56]. FGDS and Global Diet Quality Score Positive were most consistently associated with achieving &#x2265;25 g/d of fiber and &#x2265;3510 mg/d of potassium across contexts. CONCLUSIONS: Low-burden data collection tools yield valid metrics, enabling high-frequency monitoring of healthy diets across contexts. Specifically, avoiding sweet foods and/or sweet beverages is an indicator for adherence to WHO free sugar guidelines among nonpregnant females in upper-middle-income countries, whereas metrics reflecting nutritious food group diversity strongly reflect better micronutrient adequacy and adherence to WHO guidelines for fruits and vegetables, fiber, and potassium intakes within and across contexts.

Humans

Effect of different liposomal bupivacaine concentrations in ultrasound-guided superior trunk block on postoperative analgesia and mobility: a randomized double-blind controlled trial protocol for shoulder arthroscopy.

BACKGROUND: Shoulder arthroscopy frequently causes severe postoperative pain that may impede recovery. Liposomal bupivacaine provides prolonged analgesia, and ultrasound-guided superior trunk block (STB) offers comparable analgesia to interscalene block with a lower risk of hemidiaphragmatic paralysis. However, the optimal concentration of liposomal bupivacaine for STB remains unknown. METHODS: This randomized, double-blind, controlled trial will enrol 282 adult patients scheduled for elective arthroscopic rotator cuff repair. Patients will be randomly allocated (1:1:1) to receive ultrasound-guided STB with liposomal bupivacaine 66&#x2009;mg (Group A), 44&#x2009;mg (Group B) or 33&#x2009;mg (Group C), each diluted to 10&#x2009;mL. The co-primary outcomes are (1) rest pain Numeric Rating Scale (NRS) score at 48&#x2009;h post-surgery and (2) cumulative oral morphine milligram equivalents (MME) consumption within 0-48&#x2009;h after surgery. Secondary outcomes include rest pain NRS scores at 6, 24 and 72&#x2009;h; motor function assessed by Muscle Balance Scale, Bromage score and American Shoulder and Elbow Surgeons (ASES) score at 6, 24, 48 and 72&#x2009;h; and Quality of Recovery-15 (QoR-15) score at 24 and 48&#x2009;h. DISCUSSION: This study will provide evidence on the optimal concentration of liposomal bupivacaine for STB in arthroscopic shoulder surgery, aiming to achieve effective and prolonged analgesia without compromising shoulder mobility.

Humans

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (&#x394;CAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p&#x202f;=&#x202f;0.049), particularly for those with higher non-planning impulsivity (p&#x202f;=&#x202f;0.012). In participants randomized to CPT improvement in PTSD symptom severity (&#x394;CAPS) was negatively related to baseline total impulsivity (p&#x202f;=&#x202f;0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

Humans

Structured robotic colorectal training in a non-tertiary NHS hospital: a 502-case consecutive cohort implementation study.

Robotic-assisted colorectal surgery has expanded rapidly across NHS practice in the UK. Structured unit-wide training pathways are essential for safe technology adoption, yet published outcome data from non-tertiary hospitals remain limited. This study describes the implementation and feasibility of a unit-wide robotic colorectal program at a high-volume non-tertiary hospital, reporting outcomes across 502 consecutive resections performed by eight consultant surgeons and presenting these in the context of nationally published benchmarks. A retrospective cohort study of 502 consecutive robotic colorectal resections performed at York Teaching Hospital between May 2022 and December 2025. Eight consultant surgeons (A-H) participated in a structured four-phase training pathway incorporating simulation training, proctored cases, complexity-based case progression, and formal credentialing. Primary outcomes were 30-day mortality, unplanned return to theatre (RTT), and anastomotic leak (AL). Anastomotic leak was calculated using only patients who underwent anastomosis as the denominator. Procedure-stratified and individual surgeon outcomes with 95% confidence intervals were reported. Risk-adjusted cumulative sum (RA-CUSUM) analysis was performed to evaluate learning curves. Outcomes are presented descriptively alongside nationally published reference data; no formal statistical comparison against national benchmarks was performed. 502 robotic colorectal resections were performed. Mean patient age was 70.0 &#xb1; 11.3&#xa0;years; 58.4% were male. Median ASA grade was III. The indication was malignancy in 89.2% of cases. Length of stay was non-normally distributed and is therefore reported using median and interquartile range in the revised analysis. Key outcomes: - 30-day mortality: 1.0% (5/502; 95% CI 0.4-2.3%) - Unplanned return to theatre (RTT): 5.2% (26/502; 95% CI 3.6-7.5%) - Anastomotic leak (AL): 3.3% (15/450; 95% CI 2.0-5.5%; denominator = patients with anastomosis) - 30-day unplanned readmission: 5.0% (25/502; 95% CI 3.4-7.2%) - Conversion to open surgery: 3.6% (18/502; 95% CI 2.3-5.6%) - Lymph node yield &#x2265;12: 91.3% of cancer resections - R0 resection rate: 95.1% of cancer resections All primary outcomes fell within or below the published reference ranges used for descriptive context. RA-CUSUM trajectories were heterogeneous: no surgeon crossed the predefined upper control limit, but several curves showed later upward movement. Accordingly, the analysis is interpreted as safety surveillance rather than evidence of uniform performance improvement. RA-CUSUM monitoring showed that no surgeon crossed the predefined upper control limit; however, heterogeneous trajectories precluded a claim of uniform performance improvement.

Humans

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic skeletal condition caused by FGFR3 pathogenic variants. Infigratinib, an oral FGFR1-3 tyrosine kinase inhibitor, down-regulates key pathways in the pathogenesis of achondroplasia. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach. RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo. CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).

Adolescent

RNA dysregulation as a determinant of aging and neurodegenerative vulnerability.

In the nervous system, aging causes deterioration of cellular and molecular processes that are associated with declines in cognition, sensory perception, and motor coordination. Aging is also the strongest risk factor for neurodegenerative disease, yet the mechanisms by which aging predisposes neurons to dysfunction remain incompletely understood. While genomic instability, proteostasis decline, mitochondrial dysfunction, and chronic inflammation have dominated prevailing models, recent evidence highlights RNA dysregulation as a central component of age-associated decline. In this review, we summarize recent findings suggesting that aging progressively erodes RNA regulatory fidelity through alterations in RNA-binding protein abundance, localization, biophysical behavior, and RNA interactions. We argue that age-dependent RNA dysregulation represents an important mechanism that converges with genetic risk to drive neuronal vulnerability and neurodegeneration.

RNA dysregulation

Use of wearable technologies for physical activity promotion in older adults: A systematic review.

This systematic review, conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251055299), examined the use of wearable technologies for promoting physical activity (PA) in adults aged 60 years and older. Searches across five databases (PubMed, Scopus, Web of Science, CINAHL, Cochrane) identified 2438 records, of which only six randomized controlled trials published between 2021 and 2025 met inclusion criteria, with sample sizes ranging from 36 to 551 participants and mean ages between 65 and 79 years. Given the small number of included studies, findings should be interpreted as preliminary. The studies ranged from the standalone use of commercial trackers (Fitbit, Polar, ActiGraph) to multicomponent interventions combining wearables with physiotherapist feedback, telephone counseling, web-based platforms, or interactive cognitive-motor training. Wearables used alone, as in the REACT trial, produced small or non-significant PA effects. In contrast, interventions integrating devices with personalized feedback, professional support, or digital platforms, such as PROMOTE and TASMANIA, were associated with more consistent improvements in PA, physical function, and cognitive outcomes. Multicomponent programs, such as PEER and ICMT, reported broader benefits, including cognition, balance, and reductions in sedentary behavior, though these findings derive from individual trials and require replication. Risk of bias, assessed with the Cochrane Risk of Bias tool version 2 (RoB 2.0), was rated as "some concerns" for five studies and low for only one, mainly due to gaps in randomization reporting, missing data, and lack of preregistration. Tentatively, and based on a very limited evidence base, wearables may have greater impact when embedded within broader behavioral systems, incorporating feedback, coaching, or interactive components, rather than when used in isolation as passive monitoring tools. Adherence and psychosocial outcomes appeared related to comfort and perceived usefulness among older adults, though larger and more robust trials are needed to confirm these patterns.

Humans

Effectiveness of artificial intelligence in nursing simulation education: A systematic review, meta-analysis and bibliometric visualization analysis.

OBJECTIVES: To synthesize the roles and core functions of AI in nursing simulation education for nursing students via systematic review, quantitatively evaluate its effects on students' knowledge and skill outcomes through meta-analysis, and map the research landscape and development trends of this field through bibliometric visualization analysis. DESIGN: Systematic review, meta-analysis and bibliometric visualization analysis. DATA SOURCES: Eight electronic databases: PubMed, Web of Science, MEDLINE, ERIC, Academic Search Complete, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Chinese Science and Technology Journal Database (VIP) were employed to search studies from the time of construction to 16 December 2025. REVIEW METHODS: Studies meeting the inclusion criteria were screened. The revised Cochrane Risk of Bias tool (ROB 2) and Joanna Briggs Institute (JBI) critical appraisal checklists were used for quality assessment. Meta-analysis was performed with Review Manager 5.4, and bibliometric visualization analysis was conducted using VOSviewer 1.6.20 and Bibliometrix (based on R4.4.3). RESULTS: A total of 61 studies were included. AI primarily played two roles in nursing simulation education: peer-type new subject (n&#xa0;=&#xa0;24) and direct mediator (n&#xa0;=&#xa0;22). Meta-analysis showed that AI interventions significantly improved nursing students' knowledge (SMD&#xa0;=&#xa0;1.49, 95% CI [0.55,2.43], p&#xa0;=&#xa0;0.002) and skills (SMD&#xa0;=&#xa0;0.66, 95% CI [0.02,1.31], p&#xa0;=&#xa0;0.04). Bibliometric analysis identified that the United States of America and China were the two main contributing countries in this field, and the key motor themes included generative artificial intelligence, virtual patients, and geriatric care. CONCLUSIONS: AI exerts positive effects on nursing students' knowledge acquisition and skill enhancement in simulation education, with peer-type new subject and direct mediator as the dominant roles. Future research should focus on expanding AI applications in multi-specialty simulation scenarios, activating the data-driven value of machine learning, and strengthening international collaboration and standardization construction, so as to promote the sustainable development of AI-integrated nursing simulation education.

Humans

Exploring Immersive Virtual Reality as an Approach to Improve School Participation-Related Constructs in Children With ADHD.

BACKGROUND: School participation is frequency and involvement from person-environment transactions, not diagnosis, per the International Classification of Functioning, Disability and Health (ICF) and the family of participation-related constructs (fPRC). In this framework, the environmental and child determinants of school participation (e.g., school routines and peer/teacher context; self-regulation, activity competence and preferences) interact bidirectionally to shape everyday participation. However, many interventions still target isolated impairments, overlooking coordinated changes in capacities and context. Grounded in this contemporary view, this study aimed to investigate the impact of an immersive virtual reality (IVR) intervention on school participation-related constructs in children with ADHD. METHODS: The study included 92 children aged between 7 and 12&#x2009;years diagnosed with ADHD. Participants were randomly assigned into intervention (n&#x2009;=&#x2009;46) and control (n&#x2009;=&#x2009;46) groups. Both groups completed the School Participation Questionnaire (SPQ) and Bruininks-Oseretsky Test of Motor Proficiency Test 2 Brief Form (BOT2-BF) assessment prior to the intervention. The intervention group received an IVR intervention program twice a week for 8 weeks. During this period, the control group did not receive additional therapy. At the end of the 8 weeks, the SPQ was readministered to both groups. RESULTS: Baseline characteristics showed no significant differences in SPQ and BOT2-BF results between groups, confirming homogeneity prior to intervention. Following the intervention, the study group demonstrated significant improvements across all domains of the SPQ (doing, being, symptoms and environment), with large effect sizes for SPQ total score (d&#x2009;=&#x2009;0.978) and subdomains (d&#x2009;=&#x2009;0.452-0.910). In contrast, the control group showed no improvements and even declines in subdomains. Post-intervention, between-group comparisons revealed significant differences favouring the study group across all domains (p&#x2009;<&#x2009;0.001), with large effect sizes (d&#x2009;=&#x2009;0.878-1.165). CONCLUSIONS: Findings suggest that the IVR program was associated with improvements in teacher-rated environmental and child determinants of school participation (SPQ domains) in children with ADHD.

Humans

[Tafluprost/timolol fixed-dose combination versus tafluprost monotherapy for open-angle glaucoma and ocular hypertension: a multicenter, randomized, double-blind, parallel-group trial].

Objective: To evaluate the efficacy and safety of a preservative-free tafluprost/timolol maleate fixed-dose combination compared with preservative-free tafluprost monotherapy in Chinese patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: This was a multicenter, randomized, double-blind, parallel-controlled clinical trial conducted across 25 centers, including the Eye & ENT Hospital of Fudan University, from January 2019 to November 2022. Patients diagnosed with OAG or OHT who required enhanced intraocular pressure (IOP) reduction after a 4-week washout period were enrolled. Participants were randomized 1&#x2236;1 to receive either tafluprost/timolol or tafluprost once daily for 3 months. The primary endpoint was the change from baseline in mean diurnal IOP (the average of measurements at 8:00, 10:00, and 16:00) at Month 3. Secondary endpoints included IOP changes at individual time points and the proportion of responders achieving predefined IOP reduction thresholds. Safety was assessed via the incidence of adverse events (AEs). Analysis of covariance (ANCOVA) using the Markov Chain Monte Carlo (MCMC) method was employed for the primary endpoint; superiority was established if the upper limit of the 95% confidence interval (CI) was<0 mmHg (1 mmHg=0.133 kPa). Continuous variables in secondary endpoints were compared using ANCOVA, and responder rates were analyzed using Fisher's exact test. Results: A total of 219 patients were enrolled (tafluprost/timolol group: n=110; tafluprost group: n=109). The primary efficacy analysis set included 215 patients (tafluprost/timolol: n=107; tafluprost: n=108). Baseline characteristics were well-balanced between the two groups. The majority of patients were male [127 (59.1%)] with a mean age of (44.80&#xb1;15.71) years at screening. At Month 3, the mean diurnal IOP reduction from baseline was (6.56&#xb1;3.44) mmHg in the tafluprost/timolol group and (5.36&#xb1;2.94) mmHg in the tafluprost group. After adjusting for baseline IOP, the between-group difference was -1.312 mmHg (95%CI: -2.010 to -0.696); as the upper limit was<0 mmHg, tafluprost/timolol demonstrated superior IOP-lowering efficacy to tafluprost. Responder rates for IOP reductions of&#x2265;15%,&#x2265;25%, and&#x2265;30% were significantly higher in the tafluprost/timolol group (P=0.016, 0.028, and 0.032, respectively). The incidence of ocular AEs was 20.0% (22/110) in the tafluprost/timolol group and 26.6% (29/109) in the tafluprost group. The most common AE was conjunctival hyperemia, occurring in 2.7% (3/110) and 8.3% (9/109) of the groups, respectively. Conclusion: Compared with preservative-free tafluprost monotherapy, the tafluprost/timolol combination provides significantly greater IOP reduction in patients with OAG and OHT, while maintaining a favorable safety profile.

Humans

De Novo 2.2&#x2009;Mb 19q13.42-q13.43 Microdeletion Encompassing U2AF2: Support for a Haploinsufficiency Model.

U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential pre-mRNA splicing factor involved in the early stages of pre-mRNA splicing. To date, multiple individuals have been reported with predominantly heterozygous missense variants presenting intellectual disability, speech and motor delays, seizures, hypotonia, and thin or hypoplastic corpus callosum. Here, we describe a patient with a de novo 2.2&#x2009;Mb interstitial deletion involving chromosome 19q13.42-q13.43, encompassing U2AF2, presenting with intellectual disability, epilepsy, corpus callosum hypoplasia, dysmorphic features, and congenital heart disease. The patient's clinical features overlap substantially with those reported in individuals harboring heterozygous U2AF2 variants, supporting haploinsufficiency as a plausible disease mechanism. To our knowledge, this represents the first postnatal report of complete U2AF2 gene deletion. In addition, this is the first detailed phenotypic characterization of a distal 19q chromosomal interstitial deletion, further delineating the clinical spectrum associated with this genomic region.

Humans

Non-linear predictive modeling and comprehensive meta-analysis of rectal temperature in Santa In&#xea;s sheep: a systematic review of thermal challenges and biometerological trends.

A systematic and bibliometric review, combined with a meta-analysis, was used to adjust an equation for estimating the physiological responses of Santa In&#xea;s sheep subjected to different thermal challenges. The systematic review compiled data on physiological responses and the thermal environment, which were then used in the meta-analysis to adjust regression models. The bibliometric analysis mapped the relationships among studies, highlighting their usefulness in interpreting research findings and biases. Addressing prior methodological critiques, the core of this study involves replacing the linear approach with a non-linear segmented regression model to accurately define the Thermal Neutral Zone (TNZ). The Segmented Regression Model was crucial, establishing the upper limit of the Thermal Neutral Zone (TNZ) at an air temperature (tair) of 34.64&#xa0;&#xb0;C, where trectal begins to increase abruptly. The model, while identifying a biologically significant breakpoint, exhibited a moderate Multiple R-squared of 0.3529, highlighting the high heterogeneity and methodological variability in the current Santa In&#xea;s literature. This non-linear approach offers a biologically superior tool for identifying the onset of thermal distress.

Animals

Integration of Clinical Case Scenarios With Anatomical Dissection Teaching-Is Recall Improved Among Medical Students?

BACKGROUND: There is ongoing debate about how best to deliver anatomy teaching in a modern medical curriculum. Some studies suggest that the separation of basic sciences and clinical teaching can impact students' confidence in anatomy, which has potential long-term implications on their medical career. This suggests new pedagogic approaches to improve anatomy teaching may be beneficial. This study aimed to establish if integrating a clinical case into anatomy practical classes would improve students' anatomy recall compared to anatomy teaching alone. APPROACH: A ten minute clinical scenario was developed, which focused on the typical history, examination, investigations and management of a hip fracture patient. Medical students (n&#x2009;=&#x2009;220) currently studying lower limb anatomy were randomised by pre-assigned anatomy groups to become intervention or control. In the intervention group, students received the clinical case teaching, followed by their anatomy session. In the control group, students attended the anatomy session. Students in both groups were then assessed on hip anatomy. The intervention group also gave their perception of the clinical case. EVALUATION: This study showed that participants who received integrated teaching performed significantly better in the anatomy recall test (3.64 SD &#xb1; 0.574) than whose who had anatomy teaching only (1.95 SD &#xb1; 0.994) (chi2&#x2009;=&#x2009;185.51, p&#x2009;<&#x2009;0.00001). Most participants (93.5%; 101/108) strongly agreed/agreed that integrating clinical cases into anatomy teaching benefited their learning. IMPLICATIONS: These results suggest that students' anatomy recall may be improved by integrating clinical cases and anatomy teaching. It also suggests that students found this approach beneficial for their learning.

Humans