Cardiac fibrosis is a pathological process characterized by excessive collagen deposition and abnormal proliferation of cardiac fibroblasts. This condition can lead to impaired cardiac function and ventricular remodeling. The development of cardiac fibrosis involves multiple mechanisms, and studies confirm that epigenetic mechanisms play a crucial part in cardiac fibrosis. Maintaining ion channel homeostasis is essential for optimal cardiac function; any imbalance can induce a range of cardiovascular diseases. However, there is little in the way of a systematic overview of the epigenetic regulation of ion channels contributing to cardiac fibrosis. This review systematically summarizes the epigenetic mechanisms underlying ion channel-mediated cardiac fibrosis and discusses potential interventions and biomarkers, along with the challenges in this rapidly evolving field.

Delaying healthcare after episodes of violence can allow hidden injuries and trauma in older adults to worsen. It increases the risk of complications, prolonged recovery, and reduced functional independence. Such delays also heighten emotional distress, potentially leading to anxiety, depression, or long-term psychological harm.

To investigate associated factors for delayed healthcare-seeking among older adults victims of violence in Brazil, from 2016 to 2022.

A cross-sectional analysis was conducted using 154,991 reported cases of violence against individuals aged 60 years and older, extracted from Brazil's national Notifiable Diseases Information System. Delay was defined as notification to health authorities occurring ≥ 24 h after the episode (used as a proxy for delayed healthcare-seeking and system responsiveness). Multivariate logistic and spatial cluster analysis were applied to assess associated factors and regional patterns.

Nearly half of the cases involved delayed healthcare-seeking. Increased likelihood of delay was associated with being female, Indigenous, mixed-race, having behavioral or mental disorders, experiencing sexual or psychological violence, episodes involving multiple perpetrators, and those occurring at night or on weekends. In contrast, delays were less likely among individuals with physical or intellectual disabilities, those identifying as bisexual, and cases involving physical violence or self-harm. Spatial analysis revealed significant geographic disparities, with hotspots of delay concentrated in the North and Northeast regions.

Delayed access to healthcare among older victims of violence is widespread and shaped by intersecting demographic, psychosocial, and structural vulnerabilities. Strengthening community-based care, improving health system responsiveness, and addressing systemic inequities are essential to ensuring timely support for this at-risk population.

At the end of 2024 over 3,500 women were living in prison in England, many of whom have experienced prior trauma and domestic abuse and are more likely than men in prison to self-harm. Compared to women living in the community, they also have higher levels of social care needs, yet little research has been conducted to explore social care provision for this population.

We conducted surveys of healthcare managers and governors in eleven women's prisons in England and their corresponding nine local authorities (LAs), to establish how they addressed their responsibilities for women with social care needs eight years on from the 2014 Care Act. Numerical and pre-coded data were analysed in Microsoft Excel using simple descriptive methods (e.g., frequencies, percentages). Descriptive qualitative analysis was used on free-text data.

The LA survey was completed by 9/9 LA staff; the prison governor survey by 8 staff (representing 10/11 prisons); and the healthcare manager survey by 7/11 staff. Considerable variation was found between establishments in Care Act assessment rates (1% to 36%). Some prisons relied on prison officers or peer supporters who had not received adequate training/supervision to identify social care needs, although all respondents agreed that social care provision had improved since the Care Act. There was less agreement regarding arrangements for transferring assessments between LAs on release. Qualitative analysis provided insight into this and other problems, including identifying women with social care needs; transferring information; gaining access into the prison; and resolving disputes/disagreements between LAs. Several proactive initiatives to improve identification/provision, and promote wellbeing, were described (e.g., regular drop-ins; scoping the use of telecare; linking with external agencies (e.g., neurodiversity and sensory services); an enablement/reablement pathway; and advocacy).

This paper is the first to explore social care provision for women in prison in relation to the 2014 Care Act. Although provision has grown and improved since the implementation of the Act, it is patchy and often suboptimal or "gets forgotten". Potential ways forward include standardised, flexible screening processes; gender-specific adaptation of screening/assessment tools; and social care training and supervision for officers and peer supporters.

Emotional disorders are the most prevalent mental health conditions worldwide. In Spain, the limited availability of mental health professionals has led to long waiting lists, contributing to the saturation of the Spanish National Health System (SNHS). This study protocol aims to evaluate the cost-effectiveness and acceptability of the Unified Protocol delivered in group format, using two brief versions (5 and 8 sessions), through a randomized controlled trial in Primary Care centers across Spain. The study also aims to identify patient profiles responding better to each condition.

Participants diagnosed with emotional disorders will be randomly assigned (1:1 ratio) to the 5- or 8-session Unified Protocol condition. Randomization will be stratified by severity of anxiety and depressive symptoms. A minimum of 180 participants will be recruited. Assessments will be conducted up to the 6-month follow-up. Data will be analyzed using descriptive statistics, Pearson's r correlations, multiple linear regressions, t-tests, repeated measures ANOVA, hierarchical models, cross lagged panel models and effect size calculations (Cohen's d). The results of this study will explore the cost-effectiveness, and acceptability of the two brief Unified Protocol formats, as well as identify patient profiles that benefit most from each version.

Findings could improve access to evidence-based care, reduce waiting lists and identify patient profiles to guide personalized, efficient interventions while optimizing SNHS resources.

Clinical Trial Number (NCT06547450||https://clinicaltrials.gov/study/NCT06547450) with the Clinical Trial Registry (7^th August 2024).

Despite most of the world's population having poor access to mental health services, scalable interventions delivered by trained non-specialists are implemented widely in low-income and middle-income countries (LMICs). Many people do not respond to these interventions, which has led to initiatives to adopt stepped care frameworks that provide people who do not respond to initial interventions with more intensive interventions. However, to date, the efficacy and cost-effectiveness of stepped care frameworks for scalable interventions have not been evaluated in LMICs. This trial aims to evaluate effectiveness and cost-effectiveness of psychological stepped care for distressed adults in an LMIC.

We did a single-blind, parallel, randomised controlled trial in Jordan with psychologically distressed adults who were randomly assigned (1:1) to a single intervention or stepped care model. Participants were required to be aged 18 years and older, Jordanians or refugees residing in Jordan, and have scores of at least 20 on the Kessler Distress Scale. Exclusion criteria were imminent suicide risk, psychotic disorder, severe cognitive impairment, risk to the person's safety, plan to return to Syria in the next 12 months, or no telephone access. Computerised software was used for randomisation to generate random number sequences in blocks of four, stratified according to nationality status by personnel independent of the trial. Assessors were masked to intervention condition. All participants received WHO's Doing What Matters in Time of Stress (DWM) programme, which comprised a five-session guided self-help programme. For participants who reported psychological distress after DWM, those in the single intervention group received enhanced usual care, whereas those in the stepped care group received WHO's Problem Management Plus, a five-session group psychological intervention. The primary outcome was between treatment group change in anxiety and depression severity assessed at 3 months after treatment (primary outcome timepoint) based on intention-to-treat analysis. Cost-effectiveness was also assessed. The trial was prospectively registered on the Australian New Zealand Clinical Trials Registry, ACTRN12621000189820, and is completed.

Between June 8 and Oct 8, 2023, 1233 individuals were screened for study inclusion and 432 were excluded (371 due to minimal distress, 30 due to a suicide risk, and 31 decided not to proceed), resulting in 801 participants being enrolled into the study. 400 participants were randomly assigned to the stepped care group and 401 were randomly assigned to the single intervention group. 753 participants were female (94%), 48 (6%) were male, and the mean age was 40·7 years (SD 11·1). At the 3-month assessment, participants enrolled in stepped care reported greater reduction of anxiety (mean difference 1·9 [95% CI 0·6-3·2; p=0·0030; effect size 0·3 [95% CI 0·1-0·5]) and depression (mean difference 2·9 [0·9-5·0]; p=0·0050; effect size 0·3 [0·1-0·5]) than participants in the single intervention group. The incremental cost per quality-adjusted life-year gained for stepped care (in international dollars [INT$]) would be INT$23 641 and has a 76% likelihood of being cost-effective at a threshold of INT$31 879 in Jordan.

Stepped care of WHO's evidence-based scalable interventions can provide greater benefits in reducing common mental disorders compared with a single intervention. Although a more resource-demanding treatment strategy, stepped care can be cost-effective in terms of its capacity for relatively greater improvements in mental health in LMICs.

Elrha through the Research for Health in Humanitarian Crises (R2HC) programme.

For the Arabic translation of the abstract see Supplementary Materials section.

Individuals with opioid use disorder (OUD) may experience fewer barriers to treatment following incarceration if offered in-jail medications for OUD (MOUD). We aimed to identify care trajectories of community OUD treatment after incarceration and examine the association between receiving in-jail MOUD and experiencing specific community treatment trajectories.

This retrospective cohort study using matched New York City (NYC) health care administrative data included adults with OUD incarcerated on or after May 2011 and discharged during 2014-2017. We defined states of community OUD treatment at the weekly level over one year following index jail discharge and performed state sequence analysis (SSA) to identify trajectories of treatment after jail and assessed the influence of receiving in-jail MOUD on treatment trajectories.

Of 14,923 eligible individuals, 26.2% received in-jail MOUD. SSA identified eight clusters of community care trajectories: continuous methadone treatment (9.7%), methadone treatment discontinuation (3.7%), methadone treatment and reincarceration (6.7%), methadone treatment initiation (4.8%), continuous reincarceration (3.5%), short reincarceration with little community treatment (20.3%), long reincarceration with little community treatment (7.0%), and no community OUD treatment or reincarceration (44.5%). Receiving in-jail MOUD was associated with belonging to the continuous methadone treatment cluster compared to the no community OUD treatment or reincarceration cluster (adjusted OR: 12.5, 95% CI: 9.9-15.7).

We identified eight unique patterns of community OUD treatment after jail release. Receipt of in-jail MOUD was associated with belonging to the continuous methadone treatment cluster. These findings suggest that provision of in-jail MOUD could improve methadone uptake in the community.

Depression affects over one-third of US military veterans, yet substantial barriers impede access to evidence-based psychotherapy. Internet-delivered cognitive behavioral therapy (iCBT) offers promise for addressing treatment gaps, but no research has examined veteran experiences with fully self-guided digital interventions. This qualitative study explored how veterans with depressive symptoms engaged with Deprexis, a self-guided iCBT program, to inform strategic implementation within Veterans Health Administration (VHA) care systems. Semi-structured interviews were conducted with 18 veterans (mean age 55.2 years, 44% female) who completed on average 7 of 10 iCBT program modules. Reflexive thematic analysis identified patterns across five domains: treatment motivation, therapeutic mechanisms, digital format features, engagement barriers, and implementation recommendations. Veterans valued treatment autonomy, privacy, and accessibility while identifying cognitive decentering and behavioral activation as key therapeutic mechanisms. However, participants articulated a fundamental paradox: iCBT requires self-initiated engagement precisely when depression most impairs motivation. Veterans recommended a stepped-care framework matching intervention intensity to symptom severity, with primary care as the optimal entry point for mild-to-moderate presentations. For moderate severity, veterans suggested minimal external support structures including care coordinator check-ins rather than intensive therapist contact, preserving the resource efficiency enabling scalability. Veterans positioned digital CBT as serving multiple strategic functions within VHA infrastructure: standalone treatment when appropriate, bridge intervention during specialty care waitlists, treatment motivator, or therapy adjunct. Findings provide actionable guidance for deploying evidence-based digital interventions within resource-constrained systems as precision tools addressing specific treatment gaps while preserving intensive services for complex presentations.

Depression is a pervasive global mental health issue, yet access to trained professionals remains severely limited. With the rapid advancement of artificial intelligence (AI), digital tools are increasingly seen as a viable way to address this shortage. However, questions remain about how digital platforms for mental health care can be effectively designed.

This study aimed to investigate, from an end user's (patient's) perspective, the potential use scenarios, desired features, and perceived risks of AI psychotherapists in depression treatment, providing design guidelines for their development.

A grounded theory approach was applied to analyze qualitative responses from 452 individuals recruited via Amazon Mechanical Turk. Data were collected through a scenario-based online survey on AI-assisted depression treatment administered between March 2023 and May 2023. Participants responded to 3 open-ended questions regarding the potential use of AI in treating depression, the characteristics expected from an AI psychotherapist, and the associated perceived risks, along with demographic, control, and contextual measures. The open-ended responses were inductively coded into themes, with intercoder reliability established (Cohen κ=0.80). In addition, variations in themes were further examined across participant profiles, including social stigma, current depression severity, trust in an AI psychotherapist, and privacy awareness.

Participants envisioned AI psychotherapists across 5 primary scenarios: diagnosis, treatment, consultation, self-management, and companionship. Key desired features include professionalism, warmth, precision care, empathy, remote services, active listener, personalization, flexible treatment options, patience, trustworthiness, and basic treatment alternative, while critical concerns include diagnostic inaccuracy, treatment errors, privacy breach, lack of human interaction, technical malfunctions, and lack of emotional engagement. Based on these findings, a general MoSCoW (must have, should have, could have, and won't have) prioritization framework was proposed to serve as a conceptual starting point for future AI system design and empirical validation in mental health care. Notably, feature prioritization varied across user profiles: individuals with higher stigma placed greater emphasis on privacy protection, those with more severe depression prioritized precision care and timely access, low-trust users de-emphasized remote services, and privacy-sensitive individuals showed reduced preference for features requiring extensive data disclosure. These patterns highlight the need for context-sensitive design.

This study provides a patient-centered framework for designing AI psychotherapists and complements the existing literature by highlighting the importance of balancing clinical effectiveness with relational considerations. The findings offer actionable guidelines for designing AI mental health care tools that are aligned with user expectations and sensitive to individual differences.

The transition from adolescence to adulthood (18 to 25 years) is associated with an increased risk of suicidal ideation and behaviors. Suicide-focused cognitive behavioral therapies (CBTs) have been shown to significantly reduce suicidal ideation and behaviors but are not widely available to high-risk individuals. Digital therapeutics could improve access to these treatments.

This study aimed to evaluate the acceptability, safety, and potential efficacy of OTX-202 among transition-age youth (18 to 25 years) receiving mental health care outside an inpatient hospital setting.

In this phase 1 single-arm clinical trial, 59 transition-age youth with recent suicidal ideation or suicide attempts used OTX-202, a smartphone app designed to deliver suicide-focused CBT, concurrently with usual outpatient mental health care. After baseline, eligible patients completed 12 weekly assessments of suicidal ideation, depression, and anxiety.

From baseline to week 12, participants reported statistically significant, large reductions in suicidal ideation (mean difference -5.1, 95% CI -6.5 to -3.7; d=0.95). In total, 3 (5.1%; 95% CI 0%-11.2%) participants reported suicide attempts. Reductions in suicidal ideation and suicide attempt rates were consistent with results from previously published randomized clinical trials of suicide-focused CBTs. Participants rated OTX-202 in the 97th percentile of usability and completed a mean of 9.0 (SD 3.5) of 12 app modules, supporting the app's acceptability. There were no patient deaths, device-related events, or severe adverse events, supporting the app's safety.

Results support the safety, acceptability, and potential efficacy of OTX-202 for reducing suicide risk among transition-age youth.

ClinicalTrials.gov NCT06008132; https://clinicaltrials.gov/study/NCT06008132.

Depression and anxiety frequently emerge during late adolescence and young adulthood; however, many conventional and app-based interventions struggle to sustain engagement. Virtual reality (VR) exergaming, music-based activities, and social interaction each show promise for supporting young people's mental health, but their combined therapeutic value remains insufficiently tested.

This study aims to evaluate the effectiveness of a 6-week VR-based social musical exergame for reducing depressive and anxiety symptoms in young adults. The secondary objectives are to explore whether changes in basic psychological need satisfaction are associated with symptom change and to assess the effects on loneliness, presence, cardiorespiratory fitness, and in-game music-movement synchronization.

This study is a 3-arm, parallel-group randomized controlled trial. A total of 110 participants aged 18 to 25 years with mild to moderate depression or anxiety will be recruited and randomized in a 1:1:1 ratio to (1) a VR social musical exergame, (2) a matched VR solo musical exergame active control, or (3) a waitlist control receiving standardized mental health guidance. Assessments will be completed at baseline, at the postintervention assessment (week 6), and at the 1-month follow-up assessment (week 10). The primary planned comparison is the experimental group vs the active control group.

This study was approved by the ethics committee of Hunan Traditional Chinese Medical College on September 8, 2025 (YXLL202509006) and prospectively registered at ClinicalTrials.gov on March 15, 2026 (NCT07482852). Internal institutional funding had been secured. As of April 2026, the trial status was "not yet recruiting;" no participants had been enrolled, and no data analysis had been conducted. Recruitment is anticipated to begin in May 2026, with primary completion on March 1, 2028, study completion on May 1, 2028, and publication of the primary findings expected in late 2028.

This protocol describes a self-determination theory-informed, multicomponent VR intervention designed to evaluate whether adding a bundled social layer to a matched solo exergame improves short-term mental health outcomes. The trial is expected to provide initial evidence on efficacy, safety, and potential mechanisms while generating hypotheses for future dismantling and longer-term trials.

ClinicalTrials.gov NCT07482852; https://clinicaltrials.gov/ct2/show/NCT07482852.

PRR1-10.2196/83737.