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PubMed2026

Evaluating the utility of melatonin in spine surgery: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Spine surgery is increasingly performed worldwide, and acute postoperative stressors such as pain and anxiety remain highly prevalent despite historical management with opioids and other pharmacological agents. Recently, interest has emerged in melatonin administration given its endogenous physiological roles, low cost, favorable adverse event profile, and documented benefits throughout surgical literature. PURPOSE: This study aims to consolidate the existing evidence on melatonin's utility specifically in spine surgery, an area not yet comprehensively evaluated, to inform clinical practice and enhance spine surgeon comprehension. STUDY DESIGN/SETTING: Preregistered on PROSPERO, this systematic review queried PubMed/MEDLINE, CINAHL, SPORTDiscus, and Web of Science on November 21st, 2025, for studies reporting outcomes following melatonin administration in patients undergoing spine surgery. METHODS: Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Extracted variables included demographics, comparator medications, dosages, and other relevant details. Statistical analyses included frequency-weighted means (FWMs), associated standard deviations, narrative syntheses, and limited meta-analyses, where appropriate. RESULTS: A total of 6 moderate-quality randomized trials were included from 749 screened. Melatonin (3-10 mg) was administered to 227 patients (FWM age=43.3±8.6 years; 46.2% male; BMI=26.6±3.2 kg/m2), placebo to 125 patients (age=43.2±10.1 years; 60% male; BMI=28.5±4.3 kg/m2), and active pharmacologic comparators (fentanyl, gabapentin, dexmedetomidine, zolpidem) to 151 patients (age=46.6±8.9 years; 40.5% male; BMI=26.3±3.5 kg/m2). Procedures primarily involved uncomplicated lumbar laminectomies (1-4 levels), with outcomes assessed up to 24 hours postoperatively. Melatonin was associated with significant improvements in early postoperative VAS-pain scores, blood-pressure-related, analgesic-related, and anxiety-related outcomes versus placebo across most reporting studies. Compared with active pharmacologic agents, significant benefits were observed only in select nausea- and anxiety-related instances. Limited meta-analysis (n=2) demonstrated higher 24-hour VAS-pain for melatonin versus gabapentin, though mean difference was near-negligible and harbored extensive statistical constraints. CONCLUSION: Melatonin demonstrates variable utility following spine surgery, with generally consistent anxiolysis and frequent benefit versus placebo but less consistent and comparatively weaker efficacy relative to active pharmacologic comparators. Future outcome-homogenous studies incorporating more granular, expansive comparator arms and more robust quantitative analyses are needed to further elucidate melatonin's role in advancing spine care. LEVEL OF EVIDENCE: Level II.

Humans↗
PubMed2026

Health-Related quality of life (HRQoL) and health state utility values (HSUV) in patients with head and neck Cancer: A systematic review and Meta-Analysis.

BACKGROUND: Head and neck cancer (HNC) and its treatment can substantially impair speech, swallowing, eating, appearance, and social functioning, resulting in persistent reductions in health-related quality of life (HRQoL). Although the EuroQol 5-Dimensions questionnaire (EQ-5D) is widely used to assess generic HRQoL and derive health state utility values (HSUVs), EQ-5D-based evidence in HNC has not been comprehensively synthesized. This study aimed to summarize EQ-5D-based HRQoL and HSUVs in HNC, estimate pooled utility and EQ-VAS scores, explore subgroup differences, and identify predictors of poorer HRQoL. METHODS: A systematic review and meta-analysis was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420261307907). PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus were searched from inception to February 10, 2026. Studies reporting baseline EQ-5D utility values and/or EQ-VAS scores in patients with HNC were included. Random-effects meta-analyses using the DerSimonian-Laird (DL) estimator with the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment were performed to pool mean scores. Between-study variance (τ2) and 95 % prediction intervals (PI) were calculated to capture parameter dispersion. Subgroup analyses were conducted across clinical and methodological vectors. RESULTS: Twenty studies involving 7,403 patients were included. The pooled mean EQ-5D utility score was 0.79 (95 % CI: 0.75-0.83; τ2 = 0.0011; 95 % PI: 0.72-0.86). The pooled mean EQ-VAS score was 69.36 (95 % CI: 65.71-73.01; τ2 = 38.4586; 95 % PI: 55.11-83.61). Extreme heterogeneity was observed (I2 = 96.4 % and 97.1 %, respectively). Utility values were significantly higher in studies utilizing the EQ-5D-5 L than the EQ-5D-3 L version (0.82 vs. 0.76). By tumor subsite, nasopharyngeal cancer showed the highest utility value (0.85, exploratory), whereas oral cancer demonstrated the lowest (0.73). Adjusted multivariable models revealed that advanced stage, high treatment intensity, severe pharyngolaryngeal pain, dysphagia, malnutrition, and older age were robust predictors of poorer HRQoL. CONCLUSIONS: Patients with HNC experience substantial and persistent HRQoL impairment, with meaningful variations driven by tumor subsites and instrument versions. In light of the extreme heterogeneity, these pooled findings establish a macro-level, broad reference estimate rather than a fixed target. These parameters directly inform localized survivorship care planning, health technology evaluations, and cost-utility decision-making modeling in head and neck oncology.

Humans↗
PubMed2026

A Smartphone-Based Ecological Momentary Intervention for Workplace Mental Health: Randomized Controlled Trial.

BACKGROUND: Work-related stress has been widely associated with an increased risk of various mental disorders and poor mental well-being. The fast-growing mobile health services industry has provided new opportunities for workplace mental health. OBJECTIVE: This randomized controlled trial examined the effectiveness of Neurum (Neurum Limited), a smartphone-based intervention tool featuring ecological momentary assessments and interventions that aims to reduce workplace stress in real-time and real-world settings. METHODS: A total of 201 working adults were recruited for a 4-week smartphone-based intervention that incorporated cognitive behavioral therapy, mindfulness exercises, and self-regulation exercises delivered on Neurum. A simple randomization procedure was used. Participants in the intervention group were encouraged to log mood journals, complete mental health exercises, and provide user feedback whenever applicable. The key outcome was measured by the Depression, Anxiety, and Stress Scale-21 items (DASS-21; Cronbach &#x3b1;=0.87). RESULTS: The intervention group consisted of 102 participants, while the control group consisted of 99 participants. More participants dropped out from the intervention group (n=21) than from the control group (n=2; &#x3c7;21=18.259; P<.001). The final sample consisted of 178 participants (male: 85/178, 47.8%; female: 93/178, 52.2%; mean age of 34.65, SD 7.67 y). Analyses revealed that after the 4-week intervention, the DASS-21 scores decreased in the intervention group (mean difference [MD]post-pre intervention=-14.518) but increased in the control group (MDpost-pre intervention=3.319; F1,176=59.358, P<.001; &#x3b7;2=0.252). This effect was largely led by stress reduction (F1,176=64.679, P<.001; for the intervention group, MDpost-pre intervention=-6.692, while for the control group, MDpost-pre intervention=2.000). On average, participants completed 6.27 (SD 9.4) exercises and provided 9.74 (SD 18.2) mood journal logs, with a daily engagement of 4.95 (SD 6.89) minutes. However, the associations between the changes in DASS-21 scores and the numbers of exercises or mood journal logs did not reach statistical significance. CONCLUSIONS: This study primarily established the effectiveness of Neurum in alleviating depression, anxiety, and stress symptoms in noninstitutionalized working adults, with a satisfactory user retention rate. Despite potential health-related culture differences, Neurum contributed to evidence-based digital health in nonclinical settings for timely needs and general accessibility as an alternative to traditional, face-to-face, and high-cost mental health services. Future directions involving a personalized approach in online mental health services were discussed.

Humans↗
PubMed2026

Trade-offs in avian parental care: a review of theory and meta-analysis of brood size manipulations.

The selective forces shaping parental care have been studied for over 50&#x2009;years. While theoretical and experimental work has yielded qualitative progress, the large body of empirical work testing predictions about parental investment based on life-history trade-offs has yet to be synthesized. We first provide an overview of the core life-history theory exploring how selection might shape parental care. We then conduct a systematic review and meta-analysis on studies that experimentally manipulated brood size in birds, a widely used experimental approach to manipulate parental investment. We extracted 313 estimates from 62 studies representing 31 species of birds from 19 different families and tested key predictions on trade-offs in parental care derived from theory. Our analysis provides strong support for some predictions about life-history trade-offs in parental care, but weak or equivocal support for others. Specifically, we found that overall, avian parents respond to brood size manipulations as predicted by life-history theory: they increased care in response to brood enlargement, and decreased care in response to brood reductions. Furthermore, for the same relative manipulation size, responses to brood reductions were greater than responses to brood enlargements. This finding is consistent with predictions derived from life-history theory based on some types of non-linear utility curves. However, many predictions derived from theory are not well supported by our comparative analysis. Species' life-history traits such as clutch size (a measure of current reproduction), adult survival, and broods per year (two measures of future reproduction), explained little, if any, among-species variation in response to brood size manipulations. Several factors may explain this. We highlight that brood size manipulations may affect more than just perception of the value of current reproduction, such as altering parents' perception of predation risk. Importantly, these unintended consequences could lead to asymmetric responses like those we observed. Other common experimental approaches - such as hormone manipulations, altering a partner's effort, and food supplementation - often affect multiple traits or fitness components simultaneously, or may involve cues that poorly match the evolved mechanisms guiding parental behaviour. Our review of both theory and experimental approaches suggests that there are multiple opportunities for more precise experiments. We offer several recommendations for effective designs. One is improved understanding of the biology underlying the functions relating to costs and benefits, with careful consideration of not only how the manipulation will affect only one of those, but also the mechanisms that might alter how parents perceive the manipulation. We also emphasize general principles, such as assessing alternative hypotheses and devising multiple independent tests. Armed with these recommendations, we believe there are new opportunities to increase the strength of inference achieved from studies aimed at understanding the trade-offs affecting the evolution of parental care.

Animals↗
PubMed2026

The efficacy of modified psychodynamic psychotherapy for patients with schizophrenia-spectrum disorders in Germany: a prospective, single-centre, assessor-blinded, parallel-group, randomised controlled trial.

BACKGROUND: People with schizophrenia-spectrum disorders have difficulties in interpersonal functioning that remain insufficiently addressed by standard care. Despite long-standing clinical use, psychodynamic psychotherapy has little empirical support compared with other psychosocial treatments for people with schizophrenia-spectrum disorders. We evaluated the efficacy of Modified Psychodynamic Psychotherapy for Schizophrenia (MPP-S), a manualised treatment tailored to the interpersonal vulnerability characteristic of this population, plus treatment as usual (TAU), compared with TAU alone. METHODS: This prospective, single-centre, assessor-blinded, parallel-group, randomised controlled trial was conducted at the Psychiatric University Hospital of the Charit&#xe9; at St Hedwig Hospital in Berlin, Germany. Participants were outpatients aged 18-64 years who were diagnosed with schizophrenia or schizoaffective disorder and exclusion criteria included organic brain disorder, somatic illness affecting cerebral function, and current or past alcohol or illicit drug misuse requiring addiction-specific treatment. Participants were randomly assigned 1:1 in blocks of ten to MPP-S (minimum 30 sessions) plus TAU or TAU alone. Outcome assessors were masked, but participants and therapists were not. The primary outcome was psychosocial functioning, measured using the Mini International Classification of Functioning, Disability and Health Rating for Limitations of Activities and Participation in Psychological Disorders (Mini-ICF-APP) and evaluated at baseline and prespecified post-treatment (24 months) and follow-up (36 months) assessments. Analyses followed the intention-to-treat principle. Linear mixed models were used to analyse incomplete longitudinal data under a missing-at-random assumption. People with lived experience were not formally involved in the design, conduct, or reporting of this study. This trial was preregistered at ClinicalTrials.gov (NCT02576613) and is complete. FINDINGS: From Oct 12, 2015, to Dec 7, 2021, 130 participants (57 [44%] female and 73 [56%] male) were randomly assigned to either MPP-S plus TAU (n=65) or TAU alone (n=64). One participant withdrew consent to data analysis. Regarding the primary outcome of psychosocial functioning, linear mixed models showed significant group-by-time interactions favouring the intervention: estimated marginal means indicated adjusted between-group differences in Mini-ICF-APP scores of -3&#xb7;45 (95% CI -5&#xb7;51 to -1&#xb7;40; p=0&#xb7;0011) at 24 months and -4&#xb7;07 (-6&#xb7;19 to -1&#xb7;94; p=0&#xb7;0002) at 36 months. The frequency of adverse events was similar between groups. There were three serious adverse events: two participants died by suicide (one in the MPP-S plus TAU group who did not start psychotherapy and one in the TAU alone group) and one participant in the MPP-S plus TAU group was admitted to a forensic hospital. INTERPRETATION: MPP-S added to TAU could improve psychosocial functioning compared with TAU alone. Our findings suggest efficacy and possible long-term benefits of psychodynamic psychotherapy for schizophrenia-spectrum disorders and indicate its potential role alongside other psychotherapeutic and psychosocial treatments. FUNDING: Berlin Institute of Health, Deutsche Gesellschaft f&#xfc;r Psychoanalyse, Psychotherapie, Psychosomatik und Tiefenpsychologie, International Psychoanalytic University Berlin, and K&#xf6;hler-Stiftung.

Humans↗
PubMed2026

Validation of a Turkish Translation of the Stress in Emergency Healthcare Professionals: The Stress Factors and Manifestations Scale.

AIM: The primary duties of emergency healthcare professionals (EHPs) are to provide emergency patient care to acutely ill and injured individuals. Due to the nature of their work, EHPs operate under constant stress, often requiring rapid decision-making, swift action, and the delivery of necessary medical care in life-or-death situations, sometimes under inadequately safe conditions. Therefore, the aim of this study is to determine the validity and reliability of the Emergency Healthcare Professional Stress Factors and Symptoms (SEHP:SFMS) Scale in Turkish for identifying stress factors and symptoms in emergency medical care professionals providing emergency patient care services. DESIGN: A methodological study design was used in this study. METHODS: The study was conducted with the participation of 211 EHPs from employees working in emergency care institutions affiliated with the Mu&#x11f;la Provincial Health Directorate between November 2023 and June 2024. Data were collected via a face-to-face survey. Data were analysed using Lawshe content validity ratio, Kaiser-Meyer-Olkin coefficient, Bartlett test, exploratory factor analysis, principal component analysis, Varimax factor rotation method, confirmatory factor analysis, Cronbach's &#x3b1; internal consistency coefficient, convergent validity, discriminant validity, test-retest, and Spearman correlation coefficient tests. RESULTS: The linguistic translation and cultural adaptation of the SEHP:SFMS showed strong performance. The scope validity index of the scale is 0.83. The item-total correlation values of the scale were found to be between 0.486 and 0.794, and the factor loadings were between 0.474 and 0.816. Confirmatory factor analysis fit indices: &#x3c7;2&#x2009;=&#x2009;248.727; df&#x2009;=&#x2009;101; n&#x2009;=&#x2009;211; p&#x2009;=&#x2009;0.000; &#x3c7;2/df&#x2009;=&#x2009;2.463; RMSEA&#x2009;=&#x2009;0.083; CFI&#x2009;=&#x2009;0.914, SRMR&#x2009;=&#x2009;0.052, which was found to be compatible and acceptable with the proposed 3-factor model. The Cronbach's &#x3b1; reliability coefficient of the scale was 0.931, and the total variance was 61.97%. CONCLUSIONS: SEHP:SFMS is a valid and reliable tool to assess stress factors and symptoms of Turkish emergency healthcare professionals. Its use improves the quality of emergency care. PATIENT OR PUBLIC CONTRIBUTION: These study findings have been used to create a tool with Turkish validity and reliability that allows for the examination of stress factors among healthcare professionals working in emergency and critical services. Identifying and reducing stress factors among healthcare professionals is crucial for the delivery of quality healthcare services. It can also be used to develop targeted interventions and ongoing strategies to facilitate improved clinical supervision and mentoring. IMPLICATION FOR NURSING PRACTICE: Nurses in emergency departments, which are among the most stressful, dynamic, intense, life-saving, and critical environments in healthcare institutions, and where life-saving treatment is administered, are at high risk of experiencing psychological trauma. Trauma experienced in the work environment is a significant problem for nursing. The consequences of trauma negatively affect nurses and institutions. Studies show that post-traumatic stress, anxiety, depression, and burnout are commonly observed in emergency department nurses. In this sense, understanding the stress and stress factors experienced by nurses can guide future interventions. The results of this study are considered important in making visible the stress and stress factors experienced by nurses in the emergency department, and also in guiding managers and nurses working in this field in terms of preventive and protective measures.

Humans↗
PubMed2026

Performance of AI-Based Screening Tools for Obstructive Sleep Apnea Across Apnea-Hypopnea Index Thresholds: Systematic Review and Meta-Analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent but remains substantially underdiagnosed. Polysomnography (PSG) is the reference standard, but its cost and limited availability constrain large-scale case identification. AI-based screening tools may support risk stratification and referral prioritization, but their diagnostic accuracy across apnea-hypopnea index (AHI) thresholds remains uncertain. OBJECTIVE: This review aimed to systematically evaluate the diagnostic accuracy of AI-based OSA screening tools at AHI thresholds of &#x2265;5, &#x2265;15, and &#x2265;30 events/hour, with emphasis on models using non-PSG-derived inputs. METHODS: PubMed, Embase, Scopus, and Web of Science were searched for studies published from January 1, 2016, to May 3, 2026. Eligible studies included adults evaluated for suspected OSA or recruited from population-based cohorts, assessed AI-based models intended or interpretable for OSA screening, risk prediction, or screening-oriented severity classification, used PSG as the reference standard, and reported sufficient data to construct or reconstruct 2&#xd7;2 contingency tables. Diagnostic accuracy was synthesized separately by AHI threshold and input source using bivariate random-effects models, with 95% CIs and prediction intervals (PIs). Risk of bias and certainty of evidence were assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation), respectively. RESULTS: A total of 60 studies were included, of which 47 contributed data to the meta-analysis. At AHI thresholds of &#x2265;5, &#x2265;15, and &#x2265;30 events/hour, pooled sensitivities were 0.94 (95% CI 0.92-0.96; 95% PI 0.71-0.99), 0.87 (95% CI 0.84-0.89; 95% PI 0.66-0.96), and 0.83 (95% CI 0.79-0.87; 95% PI 0.61-0.94), respectively; the corresponding specificities were 0.77 (95% CI 0.69-0.84; 95% PI 0.30-0.96), 0.81 (95% CI 0.75-0.85; 95% PI 0.39-0.96), and 0.91 (95% CI 0.87-0.94; 95% PI 0.55-0.99), respectively. The corresponding areas under the summary receiver operating characteristic curves were 0.943, 0.907, and 0.920. For non-PSG-derived tools, sensitivities were 0.92, 0.85, and 0.81, and specificities were 0.70, 0.74, and 0.85 at the 3 thresholds, respectively. For PSG-derived models, sensitivities were 0.96, 0.90, and 0.85, and specificities were 0.82, 0.88, and 0.96, respectively. Exploratory subgroup analyses suggested performance variation across selected study and model characteristics, including region, algorithmic framework, data source, and validation method. CONCLUSIONS: AI-based tools showed generally favorable screening performance for OSA across clinically relevant AHI thresholds, although wide PIs suggest variable performance across future comparable populations and settings. By synthesizing diagnostic accuracy across 3 AHI thresholds and distinguishing non-PSG-derived from PSG-derived models, this review extends previous broad or modality-specific reviews and offers a clinically interpretable, pathway-specific basis for linking model performance to intended use. The findings may clarify potential roles for non-PSG-derived tools in front-end screening and referral prioritization and for PSG-derived models in reduced-channel assessment and sleep-laboratory workflow support. Given substantial heterogeneity, limited external validation, and low or very low certainty of evidence, prospective validation is needed before routine implementation.

Humans↗
PubMed2026

Holmium laser enucleation of the prostate for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

RATIONALE: A range of surgical options is available for the treatment of benign prostatic hyperplasia (BPH), including holmium laser enucleation of the prostate (HoLEP). The evidence is unclear regarding differences in functional, perioperative, and morbidity outcomes between these modalities. OBJECTIVES: To assess the effects of holmium laser enucleation of the prostate compared with other surgical treatments for lower urinary tract symptoms in men with benign prostatic hyperplasia. SEARCH METHODS: We searched multiple databases (including MEDLINE, Embase, CENTRAL, Web of Science, LILACS, and the International HTA database), trial registries, and conference abstracts through April 08, 2026. ELIGIBILITY CRITERIA: We only included randomized trials of men over 40 years of age with a prostate volume of at least 20 mL (assessed by digital rectal examination, ultrasound, or conventional imaging) who exhibited lower urinary tract symptoms (LUTS) defined by an International Prostate Symptom Score (IPSS) of eight or greater undergoing surgical interventions for BPH. OUTCOMES: The critical outcomes measured were the urologic symptoms score, the quality-of-life score, and major adverse events. The important outcomes measured were: re-treatment, erectile function, ejaculatory function, transfusions, acute urinary retention, indwelling urinary catheter duration, and hospital stay duration. RISK OF BIAS: We used the Cochrane risk of bias tool (RoB 1) to assess for potential sources of bias on a study and outcome level basis. SYNTHESIS METHODS: We pooled outcome data using the random-effects model and performed meta-analyses using the Mantel-Haenszel method. We assessed statistical heterogeneity in the pooled data by visually inspecting forest plots and using the I2 statistic to quantify it. We used the GRADE framework to assess the certainty of evidence. INCLUDED STUDIES: We included 52 trials that included 6242 participants that compared HoLEP to other surgical interventions for benign prostatic hyperplasia. The median age of participants across the studies ranged from 65 to 74 years. The baseline prostate volume ranged from 30 cc to 142 cc. Baseline IPSS scores ranged from 19.6 to 28.6 (range 0-35). SYNTHESIS OF RESULTS: We prioritized comparing HoLEP with transurethral resection of the prostate (TURP) at short-term follow-up (up to 12 months), because TURP is the long-standing reference standard and the predominant comparator in randomized surgical trials. Findings for the four remaining comparisons (laser ablation, alternative energy source enucleation, other minimally invasive therapies, and simple prostatectomy), for long-term follow-up, and for all remaining outcomes are reported in full in the review. Compared to TURP, at short-term follow-up: Critical outcomes - HoLEP may result in little to no difference in short-term urologic symptom scores measured using the IPSS (range 0 to 35; lower values reflect fewer symptoms) (MD -0.67, 95% CI -1.20 to -0.14; I&#xb2; = 93%; 14 studies, 1666 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term quality of life (range 0 to 6; lower values reflect better quality of life) (MD -0.04, 95% CI -0.23 to 0.15; I&#xb2; = 73%; 6 studies, 876 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term major adverse events (RR 0.75, 95% CI 0.35 to 1.58; I&#xb2; = 0%; 10 studies, 1147 participants, low-certainty evidence). Important outcomes - HoLEP likely results in little to no difference in re-treatment (RR 0.45, 95% CI 0.14 to 1.50; I&#xb2; = 0%; 8 studies, 813 participants, moderate-certainty evidence). - HoLEP likely results in little to no difference in erectile function (MD -0.03, 95% CI -0.47 to 0.42; I&#xb2; = 0%; 3 studies, 518 participants, moderate-certainty evidence). - Ejaculatory function: we did not find any data for this outcome. - HoLEP likely reduces the need for blood transfusion (RR 0.19, 95% CI 0.09 to 0.42; I&#xb2; = 0%; 15 studies, 1755 participants, moderate-certainty evidence). AUTHORS' CONCLUSIONS: Compared with TURP, HoLEP may achieve similar relief of urologic symptoms, similar quality of life, and similar rates of major adverse events in the first 12 months after surgery, and probably similar re-treatment rates and erectile function. HoLEP likely reduces the need for blood transfusion; this is the only advantage of HoLEP that the randomized evidence, as summarized here, supports as clinically important. There was insufficient evidence to assess outcomes in the subset of individuals with larger prostates or on anticoagulation. Future research should prioritize long-term trials reporting sexual function and urinary incontinence outcomes, recruit men with very large prostates (&#x2265; 150 cc) or on anticoagulation therapy, and evaluate cost-effectiveness and training requirements. FUNDING: No external funding was received for this review. REGISTRATION: The protocol for this review was published in the Cochrane Database 2019 (https://doi.org/10.1002/14651858.CD013291).

Humans↗
PubMed2026

Cryo-EM structure of TGFBIp fibrils driven by a corneal dystrophy-linked mutation enables design of peptide inhibitors of aggregation.

Corneal dystrophy is a heterogeneous group of diseases which manifests clinically by progressive corneal opacity and diminishing visual acuity. A group of corneal dystrophies are linked to autosomal dominant mutations in transforming growth factor &#x3b2;-induced protein (TGFBIp) and characterized by extracellular amyloid-positive deposits of unknown molecular structure. Here, we determined the cryogenic-electron microscopy (cryo-EM) structure of amyloid fibrils formed by the TGFBIp FAS1-4 domain with corneal dystrophy-linked mutation V624M. The L569 to N609 fibril core, which includes the Y571-R588 segment enriched in patient corneal deposits, forms symmetrical protofilaments with internal solvent channels. Leveraging this structure, we designed peptide inhibitors intended to bind onto fibril ends to block elongation, targeting the unequal growth of symmetrical protofilaments. Our G1 and H4 inhibitors exhibit concentration-dependent reduction of TGFBIp FAS1-4 aggregation as assessed by Thioflavin T, solubility fractionation, and electron microscopy. Our work illustrates how fibril structures can guide rational inhibitor design and suggests the targeting of protein aggregates as a therapeutic approach for corneal and ocular diseases.

betaIG-H3 Protein↗
PubMed2026

Effectiveness of exercise-based prehabilitation on pre and postoperative outcomes of patients undergoing cardiac surgery-An umbrella review of systematic reviews.

AIMS: Individuals undergoing cardiac surgery are becoming older, frailer, and less mobile. Prehabilitation has shown to improve postoperative outcomes by optimizing preoperative physical function. This umbrella review aims to pool the systematic reviews assessing the effectiveness of exercise-based prehabilitation in cardiac surgery. METHODS AND RESULTS: The review followed the PRIOR checklist. PubMed, Embase, CINAHL, Cochrane library, Scopus, Web of science, ProQuest NAHD, ProQuest HMC, Open Grey and MedNar were searched using relevant keywords from inception to 16th December, 2024. Two reviewers screened and extracted data from the included reviews and assessed primary study overlap with the corrected covered area. Methodological quality of the reviews was evaluated with the A MeaSurement Tool to Assess systematic Reviews-2 scale. Certainty of evidence was assessed using a previously developed criteria for overview of reviews. Six systematic reviews with 30 unique trials and 6705 participants were included. The interventions assessed included breathing exercises, inspiratory muscle training, and exercise training. Prehabilitation reduced length of hospital stay, postoperative pulmonary complications, and clinically improved functional capacity with a very low to moderate certainty of evidence. However, there was uncertainty regarding the effects pertaining to adverse events and quality of life. The methodological quality of all reviews was critically low. The primary trials scored poorly in the domains of selection and detection bias. CONCLUSION: Exercise-based prehabilitation might reduce length of hospital stay and postoperative complications, and improve functional capacity. However, the quality of evidence is poor, and individual discretion is required before implementing them into practice. REGISTRATION: PROSPERO: CRD42023480100.

Humans↗
PubMed2026

Impact of education protocols and physiotherapeutic management in improving pain, symptoms, activities of daily living, and quality of life in patients with knee osteoarthritis: A systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis is a debilitating condition of the knee joint and the major cause of disability globally, with an increased economic burden on healthcare. Patient education (PE) has emerged as a primary care treatment approach in chronic conditions. This review aims to evaluate the effectiveness of PE along with exercise in reducing pain, alleviating symptoms, improving activities of daily living, and promoting quality of life among individuals with knee osteoarthritis. METHOD: A systematic search was conducted across three electronic databases, PubMed, Cochrane Library, and PEDro. The search was limited to between 2020 and 2025, and included only randomized controlled trials. The Cochrane Risk of Bias Tool and the PEDro Scale were used to evaluate the methodological evidence. Statistical synthesis was analysed using mean differences (MDs) with 95% confidence intervals (CIs) under a random-effects model. RESULTS: Eight trials were included, of which four studies evaluated the four Knee Injury and Osteoarthritis Outcome Score (KOOS) domains, and three studies evaluated the Visual Analogue Scale (VAS) and KOOS activities of daily living domain in patients with knee osteoarthritis. For the meta-analysis, we assessed all five domains of the KOOS scale and VAS. Statistical analysis of the studies showed a significant reduction in pain (VAS) for the PE along with exercise group (MD&#xa0;=&#xa0;-3.28, 95% CI (-4.85; -1.70), and I2&#xa0;=&#xa0;69.6%), but there was no significant improvement in the domains of the KOOS scale. CONCLUSION: The study highlights the importance of PE along with exercise in reducing pain. It might not be more effective when compared with exercise therapy as a standalone intervention in improving ADLs, QoL, and symptoms, but it has demonstrated some degree of effectiveness. It additionally promotes self-management and self-efficacy as a physiotherapeutic rehabilitation treatment intervention.

Humans↗
PubMed2026

[Analysis of clinical phenotypes and pathogenicity of a c.4476+5G>T variant of SCN1A gene in a Chinese pedigree affected with Genetic epilepsy with febrile seizures plus].

OBJECTIVE: To explore the pathogenicity and characteristics of a heterozygous splicing variant of SCN1A gene in a Chinese pedigree affected with Genetic epilepsy with febrile seizures plus (GEFS+). METHODS: A retrospective analysis was carried out on the clinical data and results of genetic testing of a GEFS+ pedigree consisting of 5 members who had visited the First Affiliated Hospital of Zhengzhou University on July 1, 2024. Pathogenicity of the splicing variant of the SCN1A gene was validated with a minigene splicing assay. This study was approved by the Medical Ethics Committee of the the First Affiliated Hospital of Zhengzhou University (Ethics No.: KS-2018-KY-36). RESULTS: The proband, a 24-year-old female, presented with FS in conjunct with focal seizures, and both of her younger brothers had Dravet syndrome. All of the three patients had carried a c.4476+5G>T variant of the SCN1A gene, which was unreported previously. Minigene experiment verified that the variant could cause loss of the first 7 bps of exon 24 and 138 bps from exon 23 of the SCN1A gene, resulting in alteration p.V1447_1495delfs*6 and affecting splicing. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant was predicted as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION: The c.4476+5G>T variant at an intronic site of the SCN1A gene probably underlay the pathogenesis of GEFS+ in this pedigree.

Adult↗
PubMed2026

Determinants of Nonspecific Response to Treatment in Randomized Controlled Trials of Major Depressive Disorder: A Narrative Review.

The design, conduct, and interpretation of double-blind randomized placebo-controlled clinical trials in major depressive disorder (MDD) are complicated by determinants of nonspecific response to treatment (NSRT). This narrative review provides a comprehensive overview of the determinants of NSRT in randomized controlled trials (RCTs) for MDD, including the placebo effect, factors related to measurement of the primary endpoint, the inclusion of misdiagnosed patients, the relapsing-remitting course of MDD, and factors related to functional unblinding. Potential strategies to reduce the impact of the determinants of NSRT and to improve the interpretation of RCT outcomes in MDD are also summarized. These strategies include use of centralized rating and standardized rater training, independent diagnostic confirmation, optimized site selection, minimizing financial incentives, exclusion of subjects participating in multiple clinical trials, exclusion of patients with unstable major depressive episode trajectories, and use of active placebo and alternative trial designs. Uniformity among experts in the definitions of determinants of NSRT and related concepts, as well as in strategies to address them, may facilitate progress in the development of novel treatments for MDD.

Humans↗
PubMed2026

Formation of environmental persistent free radicals in soil of ammunition demolition site: Roles of 2,4,6-trinitrotoluene and heavy metals.

Environmental Persistent Free Radicals (EPFRs) are a particular type of contaminant present in soil. This study investigated the formation process, environmental behavior, and main influencing variables of EPFRs in soils contaminated with heavy metals and 2,4,6-trinitrotoluene (TNT) from an ammunition demolition site. The results showed that the concentration of total organic carbon (TOC) in the soil was negatively correlated with EPFRs (r = -0.29). In contrast, the content of TNT and copper was significantly positively correlated with EPFRs (r = 0.90 and 0.78, respectively), indicating that TNT acts as a precursor macromolecule in the formation of EPFRs in this type of contaminated soil. Transition metal Cu may be an essential carrier in EPFR production. In order to explore the possible formation mechanism of EPFRs, a simulation experiment was carried out under different temperature and light conditions. The results showed that the photolysis process of TNT was impacted by external energy sources such as heat and light. TNT was firstly adsorbed onto the surface of a transition metal (Cu), and then EPFRs were formed through further electron transfer. This is the first study to detect significant levels of EPFRs in the soil at ammunition demolition sites.

Trinitrotoluene↗