Major depressive disorder (MDD) is a prevalent mental health condition characterized by persistent feelings of profound sadness, emptiness, or hopelessness, as well as a marked loss of interest or pleasure in almost all activities. Evidence indicates that vascular endothelial growth factor (VEGF) is essential for neuronal survival, angiogenesis, and synaptic connectivity, and is also involved in stress resilience and antidepressant mechanisms, offering new perspectives on the pathophysiology of MDD. Although several studies have examined the relationship between peripheral VEGF levels and MDD, their findings remain inconsistent or inconclusive. Therefore, this updated meta-analysis was conducted to clarify the role of VEGF in the etiology of MDD.

This study aimed to conduct an updated meta-analysis to investigate the relationship between plasma VEGF levels in patients with MDD compared to healthy controls (HCs).

Four databases, PubMed, Embase, Cochrane, and Web of Science, were systematically searched for the meta-analysis from their inception until December 2024. A total of 14 case-control studies involving 2,919 participants (1,256 patients with MDD and 1,663 HCs) were included. The meta-analysis utilized both the ratio of means (RoM) and the standardized mean difference (SMD) methods to enhance interpretability and clinical relevance.

The meta-analysis confirmed that patients with MDD had significantly higher VEGF levels compared to HCs (RoM = 1.21, 95% CI: 1.06-1.38, p < 0.001; SMD = 0.45, 95% CI: 0.13-0.77, p < 0.001).

The findings suggest that elevated plasma VEGF levels are associated with MDD, as indicated by the updated meta-analysis. A potential biological link between VEGF and MDD exists, offering important insights into the underlying pathophysiological mechanisms.

Not applicable.

Academic success among nursing students is vital for developing the professional skills necessary to ensure the safety and quality of patient care. This study examines the relationship between learning approaches (Deep, Strategic, and Surface), achievement motivation, and academic performance among nursing students.

This study employed a sample of 770 participants, balanced by country (n = 110 per country) but not by year of study. With 110 nursing students recruited from each of the seven participating countries through a multi-phase process designed to ensure cross-national data integrity. The research was conducted across seven different countries: Egypt, India, Indonesia, Jordan, Oman, Saudi Arabia, and Sudan. The Approaches and Study Skills Inventory for Students, Achievement Motivation Scale and academic performance tools were adopted in this study to assess the study approaches, achievement motivation and academic performance of the nursing students respectively.

Deep learning (DL) was found to be the strongest positive factor (p < .001) for predicting high achievement, each unit increase in DL is associated with an 8.7% increase in the odds of being a high achiever (OR = 1.087), not the probability. Conversely, surface learning (OR = 0.864) and marital status (OR = 0.124) were significant negative factors; each increased the likelihood of an individual achieving a lower level of academic achievement.

Deep learning and the active cognitive search for meaning have a significant association with academic success for nursing students. This shows that deep learning is significantly more important than achievement motivation or SL. However, a "pedagogical gap" exists as engagement in all three types of learning declines during the last year, demonstrating that maintaining deep engagement is the most important, yet most at-risk, factor for achieving excellence in both clinical and academic practice.

Health-related quality of life (HRQoL) among medical students is particularly vulnerable to academic stressors, especially in populations exposed to armed conflict. This study evaluated the internal consistency and construct validity of the Arabic version of the 36-Item Short Form Health Survey (SF-36) in a cohort of medical students at a single university in Syria and examined determinants of HRQoL during the Syrian civil war.

A cross-sectional survey was conducted among 181 of 300 medical students (60.3%) from the Faculty of Medicine at Aleppo University who attended continuing medical education sessions between September and November 2024. Self-administered questionnaires captured sociodemographic and clinical characteristics, Arabic SF-36 scores across eight domains, and the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Reliability was assessed using Cronbach's α and composite reliability. Statistical associations were evaluated using t-tests, analysis of variance (ANOVA), and backward-elimination multivariable linear regression.

Participants had a median age of 21 years (IQR: 20-22), with 63.5% male. Mean PCS scores (66.6 ± 18.5) were higher than mean MCS scores (55.9 ± 21.3), indicating relatively better physical than mental HRQoL. Among the eight SF‑36 domains, Bodily Pain (74.4 ± 24.3) and Role Physical (73.5 ± 36.9) showed the highest mean scores. Lower body mass index, higher religiosity, and absence of chronic conditions were associated with better HRQoL. In contrast, smoking and daily transport exceeding two hours were independently associated with lower mental domain scores (all p < 0.05). Cronbach's alpha coefficients ranged from 0.467 to 0.91. Four of the eight domains met the conventional reliability threshold of at least 0.70, while the PCS and MCS demonstrated strong internal consistency.

The findings demonstrate that Syrian medical students at Aleppo University experience suboptimal mental HRQoL despite relatively preserved physical functioning. The Arabic SF‑36 showed acceptable overall reliability and appropriate structural correlations for the main summary components and core physical domains. However, several mental and general health domains exhibited lower item consistency. These psychometric characteristics should be considered when interpreting domain-level scores and when adapting the instrument for similar populations affected by conflict.

Identifying relevant, measurable health indicators is essential for targeting interventions and monitoring outcomes. Urban aquatic ecosystems (UAEs) provide ecosystem services, e.g. water-quality regulation, flood and temperature buffering, and contact with nature that are known to support physical and mental health. However, most articles focusing on UAEs examine environmental risks instead of human health outcomes. The aim of this scoping review was therefore to identify human health and well-being indicators associated with UAEs as reported in the literature and to map them to the WHO Global Reference List of Core Health Indicators.

A scoping review was conducted, including complementary desk research, following the Joanna Briggs Institute nine-phase method, from defining the objective to summarising the results. A literature search in three databases returned N = 5,099 records. Screening was done independently by the authors in two iterations; title/abstract and then full text using predefined inclusion and exclusion criteria. Thirty-two articles were selected.

Three health indicator domains within the health status category, one health status indicator group, and two risk related indicators associated with UAEs were identified. Within WHO's health status indicator category, health indicator domains mental health, physical health, well-being, as well as the indicator group cause-specific mortality were found. Within WHO's risk factor indicator category, the health indicators "age-standardised prevalence of insufficiently physically active persons aged 18+ years" and "age-standardised prevalence of overweight and obesity in persons aged 18 + years" were identified. Mental and physical health and well-being were mainly assessed through self-report, whereas disease-specific indicators (e.g. prevalence, mortality) were predominantly based on registry or clinical data.

This scoping review indicates that the available literature generally reports beneficial associations between UAEs and the identified health indicators, indicator group and domains; for example, improved mental and physical health, greater well-being, increased physical activity, and reduced mortality. The mapping points to several WHO-aligned indicators that merit further investigation, including those capturing potential negative impacts, such as water-related morbidity and mortality. To better assess hazards and causal pathways, future research should not only link environmental and health metrics, but do so using standardised, comparable indicators across studies and settings.

Depression in children and adolescents is a growing public health concern with lasting effects on mental and physical health. Exercise is a promising strategy for prevention and treatment; however, the comparative effectiveness of different exercise types and their doses response remains unclear. This study aimed to evaluate the effects of different exercise types on depressive symptoms and to explore their dose-response relationships using a network meta-analysis.

Six databases (APA PsycInfo, Cochrane Library, Embase, PubMed, Scopus, and Web of Science) were systematically searched, supplemented by Google Scholar and citation tracking. Randomized controlled trials involving exercise interventions in children and adolescents were included. Risk of bias was assessed using the Revised Cochrane Risk of Bias tool. Bayesian network meta-analyses and dose-response analyses were conducted using random-effects models.

A total of 41 trials with 4,563 participants were included. Mind-body exercise (MBE) was associated with the largest estimated reduction in depressive symptoms (SMD = - 1.46, 95% CrI: -2.00 to - 0.88), followed by resistance training (SMD = - 0.90, 95% CrI: -1.68 to - 0.14), aerobic exercise (AE; SMD = - 0.80, 95% CrI: -1.20 to - 0.43), interval training (SMD = - 0.60, 95% CrI: -1.43 to 0.24), and combined aerobic exercise and resistance training (AE + RT; SMD = - 0.54, 95% CrI: -1.24 to 0.13). Subgroup analyses suggested relatively larger estimated effects for AE in clinical populations and MBE in subclinical and healthy populations. Age-related differences were also observed, with AE showing relatively larger estimated effects in children and MBE in adolescents. A nonlinear U-shaped dose-response relationship was identified, with the greatest estimated effects occurring at 947 MET-min/week. Dose-response patterns varied across types, ranging from 690 MET-min/week for AE + RT to 1,130 MET-min/week for MBE.

Exercise appears to be associated with reductions in depressive symptoms in children and adolescents, although the magnitude of benefit may vary by exercise type and dose. The primary, subgroup and dose-response findings should be interpreted cautiously because of substantial between-study heterogeneity, residual uncertainty, and the overall low-to-moderate certainty of the evidence. Further high-quality studies are needed to strengthen the evidence base, confirm subgroup and dose-response findings, and assess long-term sustainability.

Not applicable.

Severe mental illness (SMI), such as schizophrenia, is associated with high physical health morbidity, extensive healthcare utilization, and substantial economic costs. This naturalistic study examined changes in resource utilization, measured as direct costs, following a psychosocial health promotion program (MINT) across social services and physical and psychiatric healthcare. Resource utilization patterns for 77 participants were assessed using the Resource Utilization of Mental Illness (RUMI) instrument during the 6-month intervention and a 6-month follow-up. Data were collected on physical and psychiatric care, social services, and contacts with the justice system. We observed significant changes in both costs and patterns of resource utilization. As anticipated, costs related to social services were unchanged. Total costs increased during the intervention period and decreased at follow-up. Costs associated with physical and psychiatric healthcare decreased during the intervention and continued to decrease during follow-up. At a profession-specific level, significant differences were observed in primary care visits: costs associated with physician visits decreased during the intervention and increased at follow-up, whereas costs related to nurse visits increased during both the intervention and follow-up. Overall, these findings suggest that the MINT intervention may modify patients' patterns of resource utilization across services in ways that better align with patients' needs.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of extracellular amyloid-β plaques and intracellular neurofibrillary tangles of Tau. It is clinically accompanied by progressive cognitive impairment and behavioral deficits. Despite extensive AD research involving amyloid-β, pharmacological strategies targeting Aβ have shown limited clinical efficacy or adverse effects in clinical trials, while lecanemab and donanemab have shown to modestly but significantly slow cognitive decline in phase III clinical trials. However, the overall limited success of Aβ-directed therapies has shifted the attention to Tau protein. Therefore, understanding the pathology and pathogenesis of Tau in the contribution to AD is important for early diagnosis and effective treatment. Under physiological conditions, Tau stabilizes microtubules, axonal transport, and synaptic integrity. However, pathological post-translational modifications have been shown to disrupt Tau-microtubule interactions, promoting its aggregation and release into the extracellular region. Increasing evidence suggests the prion-like propagation of extracellular Tau drives the disease progression across the neuronal and glial cells leading to synaptic dysfunctions. The recent diagnostic approaches involving Tau-PET and Tau-based biofluid biomarkers have improved the detection of AD pathology. Therefore, effective clearance of Tau in AD requires understanding the molecular and cellular mechanisms regulating the pathological Tau degradation. This review explains the mechanistic contribution of extracellular Tau in AD pathogenesis and the cellular consequences. This will provide a foundation for understanding the influence of Tau on AD, the discovery of potential therapeutic strategies and new treatment methods for AD.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including autonomic dysfunction. Increasing evidence suggests that PD pathology may originate in the enteric nervous system and propagate to the brain via the vagus nerve. Accordingly, structural alterations of the vagus nerve could reflect disease-related neurodegeneration and may serve as a biomarker for PD. Vagus nerve ultrasound enables non-invasive measurement of the vagus nerve by measuring the cross-sectional area (CSA). However, existing studies report conflicting findings regarding vagus nerve CSA in PD. This meta-analysis evaluates whether vagus nerve CSA is decreased in persons with PD compared to controls.

Online databases were searched up to January, 2026, for studies measuring the CSA of the vagus nerve in PD patients using ultrasound. Twelve studies with a total of 1091 participants (541 PD and 550 controls) were included. Inclusion criteria encompassed peer-reviewed studies with PD patients and controls. Quality assessment was conducted using the Newcastle-Ottawa Scale. Meta-analysis was performed using a random effects model accounting for between-study heterogeneity.

This meta-analysis showed a statistically significant reduction in CSA of PD patients compared to the controls. The mean CSA of the right and left vagus nerve was 1.97 mm² and 1.70 mm² in PD patients and, 2.21 mm² and 1.89 mm² in controls. Study quality was moderate to high but high heterogeneity was observed.

On a group level, there is a reduction of CSA of the vagus nerve in PD patients measured by ultrasound.

Poor sleep and mental health are closely linked in adolescence, yet most studies rely on self-reported sleep. We investigated cross-sectional associations between objective sleep features (sleep duration, duration variability, and onset time) and mental health outcomes in 1371 U.S. adolescents from the Adolescent Brain Cognitive Development℠ Study (ABCD^®) [year 4 follow-up; mean age 14.09 ± 0.69, 51.86% female], controlling for age, sex, race/ethnicity, and parental education. Mental health outcomes were internalizing symptoms (emotional distress directed inward) and emotion regulation, including cognitive reappraisal (reframing emotional situations) and expressive suppression (inhibiting outward expression). Sleeping ≤7.05 h (β = 0.06 [95% CI: 0.00-0.11], p = 0.036), higher sleep duration variability (β = 0.09 [0.03-0.14], p = 0.001), with stronger effects in females (interaction: β = -0.12 [-0.22 to -0.02], p = 0.020), and later sleep onset times (β = 0.06 [0.01-0.11], p = 0.030) were all associated with greater internalizing symptoms. Sleep was not linked to reappraisal (all p > 0.05). Higher variability was associated with greater suppression (β = 0.09 [0.03-0.14], p = 0.001). Conclusively, objective sleep features were differentially associated with mental health outcomes.

Fatigue is a common and disabling symptom reported following SARS-CoV-2 infection, yet the underlying biological mechanisms remain poorly understood. In this study, we investigated whether fatigue severity in individuals previously infected with SARS-CoV-2 is associated with immune and metabolic alterations in serum and whether these peripheral changes can influence hippocampal cell function in vitro. Serum cytokines, kynurenine pathway, and tryptophan-derived and monoamine-related metabolites were measured in a total of 38 individuals with past COVID-19 infection. Human hippocampal progenitor cells were exposed to 1% patient serum during proliferation and differentiation, with readouts including cytokine release, metabolite production, and markers of neurogenesis (doublecortin, DCX) and astrocytic reactivity (glial fibrillary acidic protein, GFAP; aquaporin-4, AQP4). Results show that fatigue severity correlates with lower serum levels of interleukin-8 (IL-8) and with lower levels of metabolites of the kynurenine pathway and tryptophan-derived and monoamine-related metabolites, including kynurenine (KYN) and quinolinic acid (QUIN), and 5-hydroxyindoleacetic acid (5HIAA). Exposure of hippocampal cells to serum from individuals with higher fatigue was associated with increased endogenous production of interleukin-13 (IL-13) and the kynurenine metabolite anthranilic acid (ANA) in the cell supernatant, as well as with increased neurogenesis (increased DCX expression) and enhanced astrocytic reactivity (increased GFAP expression). Notably, serum IL-8 level was inversely correlated with both cellular outcomes. Likewise, serum 5-HIAA levels were negatively correlated with IL-13 release, with mediation analysis indicating that 5-HIAA significantly mediated the association between fatigue severity and IL-13 production (71% explained). Overall, our results suggest that fatigue after COVID-19 infection is associated with neuroimmune and metabolic changes in hippocampal cells, involving peripheral serotonin metabolism (5-HIAA) and cytokine signalling (IL-13).