Arteriovenous fistula (AVF) creation initiates stage-dependent remodeling of the venous outflow tract. Neointimal hyperplasia is a common component of this response, but its post-transcriptional regulation remains unclear. Here, analyses of human AVF datasets and tissue specimens characterized RNA-binding motif single-stranded interacting protein 1 (RBMS1) expression in postoperative AVFs, whereas a day-14 mouse AVF model and cultured vascular smooth muscle cells (VSMCs) were used to investigate its role in early neointimal remodeling. Smooth muscle-targeted RBMS1 overexpression aggravated neointimal formation, whereas conditional RBMS1 deletion attenuated it in murine AVFs. In cultured VSMCs, RBMS1 overexpression enhanced proliferation, migration, and the transition from contractile to synthetic marker expression, whereas RBMS1 silencing produced the opposite effects. Mechanistically, RBMS1 bound myelin protein zero-like 1 (MPZL1) mRNA and promoted exon 5 skipping, generating the MPZL1-Δ5 isoform. MPZL1-Δ5 overexpression reproduced selected RBMS1-associated VSMC responses and increased neointimal hyperplasia in vivo, including in RBMS1-deficient mice. MPZL1-Δ5 further interacted with GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) and enhanced protein kinase B (AKT) activation, whereas G3BP1 silencing attenuated RBMS1- or MPZL1-Δ5-induced VSMC responses. Together, these findings identify the RBMS1-MPZL1-Δ5-G3BP1-AKT pathway as an important VSMC-associated mechanism contributing to neointimal remodeling during the early postoperative phase of experimental AVFs.

Odds of death from specific causes in infants, children, and adolescents in Alaska have not been quantified with vital records. We analyze the odds of death from 12 causes in individuals ≤ 18 years.

We fit a multinomial logistic regression model (n = 12 904 death records) controlling for Indigeneity, age, sex, and year of death to predict the odds of specific causes of death.

Alaska Native individuals were most likely to die from tuberculosis and respiratory infections, while non-Alaska Native individuals were most likely to die from early infant health problems and accidents/violence. Infectious diseases and nutritional and endocrine disorders were most likely in ages 0-5, while accidents/violence, cardiovascular issues, and tuberculosis were most likely in ages 10-18.

Proportionate mortality and odds of death differed significantly, reflecting the different structures of Alaska Native versus non-Alaska Native populations in the 20th century and reinforcing demographic observations in the historical record.

Although treatment approaches have been explored in internet gaming disorder (IGD), however, little is known about the specific neural activity that is associated with treatment outcomes. This study aims to establish a treatment-sensitive network that reliably predicts treatment outcomes across different interventions for IGD.

Resting-state fMRI data were collected from 90 individuals with IGD who received one of three different intervention protocols (mindfulness meditation, approach bias modification, or retrieval-aversive conditioning training). Connectome-based predictive modelling (CPM) was used to build a treatment-sensitive network to predict individual symptom reduction, then validated them on the external dataset.

The negative (r = 0.401, p <.001) and combined network (r = 0.480, p <.001) can significantly predict a reduction of addiction severity (baseline minus post-test). Specifically, the negative network was primarily centred on the motor, subcortical, and salience networks. The positive network primarily involved cerebellar-related connections. Incorporating these into a combined model significantly improved predictive accuracy, suggesting that cerebellar-related connectivity may contribute to the prediction of intervention-related clinical improvement. Finally, the treatment-sensitive network was validated in a separate data.

This study established a treatment-sensitive network based on the whole-brain connectome. These findings provide valuable empirical evidence for identifying biomarkers for IGD treatment and advance personalised therapeutic strategies.

The trial protocol was pre-registered with the Chinese Clinical Trial Registry (www.chictr.org.cn; ChiCTR2300077831(MM), ChiCTR2300075869(ApBm), ChiCTR2500095444(R-AC), ChiCTR2400090834(SAE)).

Fetal alcohol spectrum disorder (FASD) represents a range of neurodevelopmental outcomes from prenatal alcohol exposure for which there are few interventions. Preclinical studies have identified choline as a potential treatment for cognitive deficits in FASD. We previously conducted three randomized controlled trials (RCTs) in children under age 6 and reported on memory benefits following all three trials. Two RCTs compared a fixed 500 mg daily dose to placebo, and the third RCT tested a weight-adjusted choline dose. Here, we report on a longitudinal follow-up 5 years post-study completion.

The RCTs included 2.5- to 5.9-year-old children with FASD who received choline (n = 53) or placebo (n = 51). Participants described here (n = 28 choline; n = 30 placebo) were 9.1 years old on average at follow-up. Of these, 9% had fetal alcohol syndrome (FAS), 43% partial FAS (PFAS), and 48% alcohol-related neurodevelopmental disorder (ARND). Parents completed a diagnostic interview and behavior checklists while participants completed assessments of general cognitive ability, executive functioning, and memory.

Participants who received choline in the initial RCT showed a medium effect size performance advantage (9.1% better) for non-verbal IQ and a medium effect size advantage (11.3% better) for working memory over placebo. Age at enrollment did not explain significant variance in outcome but choline dose was significantly associated with non-verbal IQ and working memory (higher dose contributed to better performance at follow-up). High rates of anxiety disorders and impulse-control disorders were observed. While there were no statistically significant differences in mental health diagnoses for choline versus placebo, there were some differences that neared significance.

Very few RCTs have been conducted in FASD, and interventions targeting cognitive functioning are needed. The data reported here suggest that choline supplementation has long-lasting neurodevelopmental benefits, especially in non-verbal IQ and working memory for individuals with FASD.

Age-related loss of lean mass is a hallmark of sarcopenia and a contributor to functional decline and morbidity in ageing populations. This study aimed to identify long-term determinants of lean mass during ageing.

Data from 3033 participants (ages 20-96 years; 49% women) in the Geelong Osteoporosis Study were analysed using linear mixed effect models with random intercepts. Appendicular lean mass (ALM) was derived from arm and leg lean mass measured using dual-energy X-ray absorptiometry. Time-varying covariates were included; missing data were imputed using predictive mean matching.

Over 16.7 years (IQR 9.7-23.2), women and older participants had lower ALM (β = -8.36; 95% CI -8.58, -8.15; β = -0.07; 95% CI -0.08, -0.06). Higher ALM was associated with socio-economic status (0.33; 0.14, 0.51), dietary calcium intake (0.46; 0.20, 0.67), femoral neck BMD (0.38; 0.29, 0.47) and thyroid hormone therapy (0.52; 0.04, 0.99). Physical inactivity (-0.48; -0.65, -0.31), smoking (-0.24; -0.46, -0.06) and stroke history (-0.51; -0.96, -0.07) were associated with lower ALM. Non-linear associations were observed for follow-up duration (fu: β = -0.16; fu²: β = 0.01; -p < 0.001), body mass index (BMI: β = 0.55; BMI²: β = -0.00; p < 0.001), systolic blood pressure (SBP: β = 0.06; SBP²: β = -0.00; p < 0.001), serum C-terminal telopeptide of type I collagen (CTx: β = 0.14, p < 0.001; CTx²: β = -0.01, p = 0.03) and high-sensitivity Creactive protein (hsCRP: β = -10.38; hsCRP²: β = 11.70; -p < 0.001). In fat-mass-adjusted models, low-density lipoprotein cholesterol (0.14; 0.04, 0.24) and triglycerides (0.22; 0.11, 0.33) were positively associated with ALM, whereas high-density lipoprotein cholesterol (-0.53; -0.81, -0.25) was inversely associated with ALM.

Sociodemographic, lifestyle, anthropometric, clinical, biochemical and treatment-related factors show independent associations with longitudinal changes in ALM.

Home visiting programmes are widely used to support families of preterm and low-birthweight (LBW) infants after hospital discharge, yet evidence on their effectiveness is limited and of variable quality, particularly in low- and middle-income countries (LMICs). A comprehensive, up-to-date review was needed to inform healthcare decisions.

To assess the effectiveness of home visits following hospital discharge compared to standard of care or no home visits, for families/caregivers of preterm or LBW infants to reduce morbidity and mortality and enhance health and well-being.

We searched CENTRAL, MEDLINE, CINAHL, Scopus, Web of Science, ClinicalTrials.gov, and the WHO ICTRP, together with reference checking, to identify eligible studies. The latest search date was April 2026.

We included randomised controlled trials (RCTs) of preterm and LBW infants and their caregivers comparing home visits after discharge from hospital with no home visits or standard of care including home visits. There were no restrictions on language or publication status.

Our critical outcomes included all-cause mortality, neurodevelopment, morbidity, growth, breastfeeding rates, exclusive breastfeeding, and emergency hospital visits. Important outcomes were hospital readmission rates, maternal/parental emotional well-being, and maternal-infant interaction.

We used Cochrane's RoB 2 tool to assess the risk of bias.

We synthesised results for each outcome in meta-analysis where possible, using random-effects models to calculate risk ratios (RRs) for dichotomous outcomes, mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes, and hazard ratios (HRs) for time-to-event outcomes, along with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for each outcome.

We included 35 RCTs, of which 28 (12,021 infants and 10,056 mothers/caregivers) contributed data to our prespecified outcomes. Most studies were from high-income countries; however, approximately 70% of participants were from a large study in India contributing data to comparison 2. The content, timing, duration, and frequency of home visits varied widely. Twenty-one studies contributed data to meta-analyses.

Home visits versus no home visits The effects of home visits on all-cause mortality at one year are very uncertain (RR 3.08, 95% CI 0.13 to 73.27; 1 study, 79 participants). Home visits may have little to no effect on cognitive development (SMD 0.06, 95% CI -0.17 to 0.29; 3 studies, 287 participants), and likely have little to no effect on motor development (SMD -0.02, 95% CI -0.36 to 0.33; 1 study, 127 participants). The effect on morbidity, specifically on diarrhoea at six months, is very uncertain (RR 0.71, 95% CI 0.42 to 1.19; 1 study, 179 participants). Home visits likely have little to no effect on growth, specifically weight-for-age z-scores (WAZ) at six months (MD -0.09, 95% CI -0.36 to 0.18; 1 study, 179 participants). Home visits likely increase the proportion of infants breastfeeding at six months (RR 1.26, 95% CI 1.16 to 1.37; I² = 0%; 4 studies, 1217 participants) and may result in a large increase in exclusive breastfeeding at six months (RR 2.31, 95% CI 0.85 to 6.29; 3 studies, 1129 participants). The certainty of the evidence ranged from moderate to very low due to risk of bias and imprecision. More intensive home visits versus less intensive home visits (part of standard of care) Home visits with community-initiated kangaroo mother care likely reduce all-cause mortality at 6 months (HR 0.75, 95% CI 0.60 to 0.93; 1 study, 8402 participants), likely have little to no effect on cognitive (MD 0.21, 95% CI -1.77 to 2.19; 1 study, 552 participants) or motor development (MD -0.85 95% CI -2.59 to 0.89; 1 trial, 552 participants) at 12 months, and likely reduce morbidity, specifically rates of diarrhoea slightly at 3 months (RR 0.94, 95% CI 0.85 to 1.04; 1 study, 7654 participants) and the risk of possible serious bacterial infections slightly at 28 days (RR 0.89, 95% CI 0.82 to 0.97; 1 study, 8384 participants). They likely have little to no effect on WAZ at six months (MD -0.01, 95% CI -0.06 to 0.04; 1 study, 7086 participants) and likely reduce the proportion of infants who are severely underweight at six months slightly (RR 0.95, 95% CI 0.87 to 1.04; 1 study, 6641 participants). More intensive home visits may have little to no effect on breastfeeding at six months (RR 1.18, 95% CI 0.88 to 1.59; 1 study, 308 participants), and their effect on exclusive breastfeeding at six months is very uncertain (RR 1.97, 95% CI 0.19 to 20.62; I² = 84%; 3 studies, 7091 participants). The certainty of the evidence was moderate for all outcomes except for breastfeeding and exclusive breastfeeding, for which it was low and very low, respectively. The certainty of evidence was downgraded for risk of bias, imprecision, and indirectness. No study in either comparison reported on emergency hospital visits.

Home visits likely improve breastfeeding and may improve exclusive breastfeeding compared to no home visits. They may have little to no effect on cognitive development, and likely have little to no effect on motor development or growth. The effects on mortality or diarrhoea are very uncertain. In places where home visits are already implemented, enhancing them so that they are more intensive than the standard of care (i.e. more frequent, longer, delivered by specialised personnel, with kangaroo mother care, etc.) likely reduces mortality, morbidity, and the risk of underweight. However, they likely have little to no effect on cognitive and motor development or WAZ, and may have little to no effect on breastfeeding rates. The effects on exclusive breastfeeding are very uncertain. Better-quality studies are needed, particularly in LMICs. There is a need for studies reporting on the critical outcome of emergency hospital visits, and to standardise outcome measures reported in this area of research, particularly for mental health and neurodevelopment outcomes.

This review was conducted for the GELA project (africa.cochrane.org/projects/GELA) which is funded as part of the EDCTP2 programme (grant number RIA2020S-3303-GELA) supported by the European Union.

Protocol: CRD42024496298 registered on 15 January 2024 (PROSPERO), available at https://www.crd.york.ac.uk/PROSPERO/view/CRD42024496298.

Psychogenic nonepileptic seizures (PNES), also termed functional seizures, are episodes that resemble epileptic seizures but occur without the abnormal ictal electrical activity characteristic of epilepsy. PNES is frequently associated with trauma exposure, post-traumatic stress disorder (PTSD), and abnormalities in autonomic regulation. Emerging evidence suggests that altered interactions among limbic, autonomic, and motor networks may contribute to symptom generation. Cervical sympathetic blockade (CSB), including stellate ganglion block techniques, has been investigated as an intervention for PTSD through modulation of sympathetic activity; however, CSB has not been established as a treatment for PNES. This case report describes an unexpected and subsequently reproducible reduction in PNES following CSB performed for severe, treatment-refractory PTSD, and considers a possible relationship between sympathetic modulation and trauma-associated functional seizures. A 27-year-old woman with severe PTSD and approximately 30 seizure-like or syncopal episodes per day was referred for CSB because of persistent PTSD symptoms despite prior conventional treatment. PNES was not the primary indication for the procedure. Ultrasound-guided CSB was performed at the C6 and C4 cervical sympathetic chain levels using 0.5% bupivacaine. Bilateral procedures were staged 24 hours apart as a safety precaution. Following CSB, PTSD symptoms improved, while the reduction in PNES occurred on a more delayed time course. Seizure-like and syncopal episodes progressively decreased and ultimately ceased approximately two months after treatment. The patient subsequently regained functional independence. Approximately one year later, following recurrence of symptoms and repeat CSB, a similar delayed pattern of seizure reduction and elimination was observed again. No major procedural complications occurred. The delayed but reproducible reduction and cessation of PNES following two separate courses of CSB suggests a possible association between cervical sympathetic modulation and functional seizure activity in a patient with severe trauma-related autonomic dysregulation. The mechanism is unknown, and the delayed response differs from the more rapid symptomatic improvement commonly reported following sympathetic blockade for PTSD. Potential downstream autonomic or neuroimmune effects may warrant investigation. This single-patient observation does not establish causality or support CSB as an established treatment for PNES, but it is hypothesis-generating and supports further prospective study of sympathetic modulation in carefully characterized patients with trauma-associated functional seizures.

Parental stress, a key risk factor for child maltreatment, is rising. The Lighthouse Parenting Program (LPP) shows promise in improving mentalizing and reducing parental burden. However, numerous barriers can hinder participation in face-to-face prevention programs. Digital interventions might help overcome barriers, with serious games considered particularly suitable for promoting intervention adherence. This study evaluated the feasibility of a mobile game prototype to support parental mentalizing and reduce stress.

Feasibility was assessed in a one-group pretest-posttest study. The low-fidelity prototype was co-designed with burdened parents and based on the LPP and the Mediational Intervention for Sensitizing Caregivers. Parents are supported in reflecting on their own and their child's mental states in challenging parent-child interactions. Eligibility criteria included age ≥ 18 years, at least one child (age 0-14), an Android smartphone and sufficient language skills. Primary outcomes were recruitment, satisfaction, usability, and prototype use. Secondary outcomes include stress, depressive symptoms and mentalizing. Post-assessment followed a 10-day intervention phase.

Recruitment took four weeks, yielding N = 26, exceeding the target of N = 22. Usability was rated good (SUS: M = 77.76, SD = 10.96, grade B+), though satisfaction was low (CSQ-I: M = 18.74, SD = 4.47). Nineteen participants (73.1%) used the prototype for 11 min on average. Depressive symptoms and stress decreased from pre- to posttest.

Low satisfaction likely reflects the prototype's preliminary stage in this proof-of-concept study, with limitations regarding content, design, and gamification. Usability and feedback along with exploratory outcomes were promising, although feasibility has not been fully achieved. A high-fidelity version needs to be evaluated in future studies.

Background The surgical management of cerebral arteriovenous malformations (AVMs) requires a meticulous balance between complete nidus eradication and the preservation of adjacent normal physiological structures. While the elimination of true malformed, nidal-draining veins is mandatory to avoid intraoperative rupture, sacrificing adjacent, non-malformed, medial cortical, and deep venous channels can cause localized venous congestion, tissue infarction, and poor functional outcomes. Objective This study analyzed the clinical, radiological, and functional outcomes of a deliberate microsurgical strategy focused on preserving critical medial venous pathways during AVM resection in an early patient series. Materials and methods A retrospective study was conducted on a consecutive series of 16 adult patients (aged >18 years) who underwent micro-neurosurgical resection of cerebral AVMs (Spetzler-Martin grades I-IV) at a single private academic institution between 2018 and 2025. Preoperative baseline features, clinical presentation (hemorrhage, seizures, focal deficits), and structural profiles were documented. Microsurgical dissection emphasized circumferential nidal isolation with strict preservation of non-nidal medial veins. Long-term functional assessment was evaluated using the Patient-Reported Outcomes Measurement Information System (PROMIS) score and the modified Rankin Scale (mRS) at a minimum of six months postoperatively. Results A total of 16 patients were included in the study, of whom 10 were male (62.5%) and six were female (37.5%). Primary clinical presentations included intracranial hemorrhage in 10 patients (62.5%), seizures in eight patients (50.0%), and focal deficits in nine patients (56.3%). Complete angiographic eradication of the AVM nidus was achieved in all 16 patients. No perioperative mortality was observed. Postoperative outcome assessment demonstrated improvements or stabilization in functional capacity. Favorable neurological recovery, defined as mRS 0-2, was documented in 14 patients (87.5%), supported by increases in PROMIS physical and mental health T-scores. No delayed venous infarction or hemorrhagic transformation occurred in any patient. Conclusions In this early clinical series, prioritizing the integrity of non-malformed medial veins during cerebral AVM surgery was a safe, effective, and anatomically sound strategy. Preserving healthy venous pathways surrounding the malformation limits the incidence of secondary venous hypertension, leading to exceptional functional preservation and minimal morbidity across a range of Spetzler-Martin grades.

Childhood adversity (CA) is a robust predictor of psychopathology later in life and has been linked to numerous transdiagnostic symptom presentations. One such presentation, irritability, has garnered increasing interest given its presence across internalizing and externalizing disorders and associations with greater functional impairment. Preliminary work has demonstrated associations between CA and irritability; however, no systematic review or meta-analysis has examined these associations or the mechanisms by which these constructs are connected.

PubMed, PsycInfo, and Web of Science were searched from inception to October 2025, for empirical English articles published in peer-reviewed journals that included measures of CA and irritability (or trait anger, a closely related construct) and examined their statistical relationship. All procedures used in this review were consistent with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines.

A total of 1839 abstracts were screened, resulting in 208 articles reviewed and 109 articles ultimately included. Random-effects meta-analysis identified a positive relationship between CA and irritability or trait anger in association (pooled association r = 0.22, 95% CI [0.19-0.24]) and group comparison (Hedges' g = 0.53, 95% CI [0.35-0.71]) studies across the lifespan. Additionally, the review identified concurrently measured psychological (i.e., emotion dysregulation, narcissism, shame, adult attachment) variables that statistically mediated the relationship between CA and irritability or anger.

Findings support robust associations between early adversity and irritability or trait anger across the lifespan. Limitations and suggestions for future empirical studies are discussed.