• NEDD9 inhibits ox-LDL-induced endothelial anoikis to attenuate endothelial cell injury.
    2 weeks ago
    This study aims to explore the action of the anoikis gene in the vascular endothelial cell injury.

    The set of genes associated with anoikis was utilized for conducting enrichment analysis on the Gene Expression Omnibus (GEO: GSE100927) dataset to identify the common genes linked to Atherosclerosis. Subsequently, the expression levels and pathway enrichment of anoikis genes in the GSE100927 dataset were examined. The LASSO method was employed for reducing dimensionality in modeling to identify genes correlated with Atherosclerosis and to establish an anoikis score. The validation of the expression of neural precursor cell-expressed developmentally down-regulated 9 (NEDD9), FOSB, and ERCC1 in ox-LDL-induced bEnd.3 cells was carried out using RT-qPCR. Atherosclerotic mice were established to evaluate NEDD9 expression. The impact of overexpressing or silencing NEDD9 on anoikis in ox-LDL or detachment-induced bEnd.3 cells or Human Umbilical Vein Endothelial Cells (HUVEC) was assessed through CCK-8, EdU, and flow cytometry assays.

    Based on anoikis gene analysis, NFIL3, NR4A3, ADAMTS4, NEDD9, STX17-AS1, and CSF3 were found to be under-expressed, while FOSB and ERCC1 were found to be over-expressed in the atherosclerosis group compared to the normal group. LASSO regression analysis yielded an anoikis score = -9.522e-01 × NFIL3-3.410 × NEDD9 + 2.728e-01 × ADAMTS4 + 1.178 × FOSB +5.896e-15 × ERCC1 + 1.558e+01. Compared with the blank group, NEDD9, FOSB, and ERCC1 were under-expressed in the ox-LDL intervention group. NEDD9 protein was significantly decreased in the arterial tissues of atherosclerotic mice. si-NEDD9 promoted an increase in ROS and apoptosis levels in the bEnd.3 cells intervened by ox-LDL. Transfection with oe-NEDD9 increased the viability of bEnd.3 cells, upregulated the ITGB1 and E-cadherin proteins level, while decreasing ROS and apoptosis levels induced by the ox-LDL and detachment. Overexpression of NEDD9 also reduced HUVEC anoikis induced by detachment.

    A preliminary atherosclerotic anoikis model was established to predict endothelial cell injury. Overexpression of NEDD9 attenuated ox-LDL and detachment-induced endothelial cell anoikis in vitro, suggesting a potential protective role.
    Cardiovascular diseases
    Care/Management
  • Ostwald Ripening for Gas Bubbles and Decompression in Diving.
    2 weeks ago
    The Ostwald ripening phenomenon for gas bubbles in a liquid consists mainly in gas transfer from smaller to larger bubbles. While the phenomenon itself is well known, the consequence of the temporal evolution of bubbles in the bloodstream in human physiology lacks deeper investigation.

    In this work, a series of direct experiments was carried out in which the Ostwald ripening for air bubbles in a viscous fluid was reproduced. There, the time evolution of the bubbles' mean radius, number of bubbles, and radius size distribution was measured, where the initial bubble distribution behaves like a Tsallis (q-Weibull) distribution.

    The results show the usual behavior of wet foam, where smaller bubbles disappear, whereas the larger bubbles, potentially dangerous for the diver, grow, and the number of bubbles decreases in time. On the other hand, a long-time power-law regime was found with an exponent smaller than that of the LSW (Lifshitz-Slyozov-Wagner) model, and the radius size distribution showed positive asymmetry throughout the experiment.

    From the results obtained, it is presumed that such a bubble broadening effect could contribute, even minimally, to decompression illness: decompression sickness and arterial gas embolism. This conjecture is reinforced by the preliminary results of Ostwald broadening to RGBM (Reduced Gradient Bubble Model) decompression schedules for a closed-circuit rebreather (CCR) dive to 420 feet of seawater (fsw) (128 meters of seawater (msw)) with a 21/79 Heliox gas mixture, where the first decompression stops lengthening time thanks to Ostwald ripening is at the Pyle-type deep stop, a stop at the half bottom depth, 210 fsw (64 msw).
    Cardiovascular diseases
    Care/Management
  • Cell-death-driven plaque evolution: macrophage fate and opportunities for targeted therapy.
    2 weeks ago
    Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease in which pathological progression is profoundly regulated by macrophage fate determination mechanisms. This review explores how macrophages derived from hemogenic endothelial cells and bone marrow contribute to disease development, functioning either as tissue-resident cells or via systemic circulation. These macrophages drive the plaque progression via three major cellular fates: foam cell formation, polarization, and programmed cell death. Impaired cholesterol efflux, together with enhanced scavenger receptor expression induced by M1 macrophage polarization, are key features of macrophage-derived foam cells. The dichotomous polarization of macrophages into M1 and M2 phenotypes forms the basis of their complex regulatory roles within the plaque microenvironment. Moreover, recent advances in sequencing technologies have uncovered additional macrophage subsets, whose specific contributions to AS progression remain to be fully elucidated. Adopting a framework that links the macrophage life cycle with AS, this review discusses the critical roles of macrophages in AS progression from the perspectives of classical (M1/M2) and various non-classical cell classifications, by delineating the macrophage life cycle from origin to distinct cellular fates within the plaque environment. Concurrently, we summarize potential therapeutic strategies targeting these processes, including metabolic reprogramming, immunomodulation, epigenetic regulation, and innovative drug delivery systems, which provide multi-layered approaches for plaque stabilization while remaining subject to substantial limitations. Overall, we emphasize the unique fate trajectories of different macrophage lineages in AS progression, their multifaceted impact on AS pathological outcomes, and recent advances in potential targeted therapeutic strategies.
    Cardiovascular diseases
    Policy
  • Mental Health of Caregivers of Adults With Neurodevelopmental Disabilities.
    2 weeks ago
    As individuals with neurodevelopmental disabilities transition to adulthood, the experiences of their caregivers change, and caregivers' roles may be different from when their children were young. During this transitional period, there are few integrated supports for caregivers, which can affect their mental health.

    Using a sample of caregivers (N = 106), this study aimed to identify protective and risk factors of caregiver mental health outcomes including the behavioural characteristics of their adults with neurodevelopmental disabilities (at age 18), sociodemographic, and psychosocial factors in a well-characterised longitudinal sample.

    Sociodemographic factors and psychosocial characteristics, and not characteristics of their adult children, are robust predictors of caregiver mental health during middle age (mean age = 56.81, SD = 5.39).

    We discuss important formal and natural supports that can work together to promote caregivers' mental health as their children transition to adulthood.
    Mental Health
    Access
    Advocacy
  • Intensified return to work clinical aftercare for sick-listed employees with diagnosed mental disorders in Germany: effects of a multicentre randomized controlled trial.
    2 weeks ago
    Mental disorders are a leading cause of sickness absence and disability in Europe. They often follow chronic or recurrent patterns, hindering a sustainable return to work (RTW). In Germany, RTW aftercare interventions focusing on maintaining recovery and minimizing relapse among employees transitioning from psychiatric treatment to the workplace are scarce. We therefore developed an intensified RTW clinical aftercare program (RTW-PIA). This study aimed to (i) evaluate the effectiveness of RTW-PIA in addition to Care as Usual (CAU) on achieving sustainable RTW (SRTW) compared to CAU only, (ii) assess its impact on secondary outcomes, and (iii) explore potential moderators.

    This multicentre randomized controlled trial, conducted in psychiatric outpatient clinics, included sick-listed employees diagnosed with a mental disorder. Participants (N = 484) were randomized to RTW-PIA + CAU (n = 240) or CAU only (n = 244). RTW-PIA is an 18-month multimodal aftercare combining medical-psychotherapeutic and work-oriented components. Primary outcome was self-reported SRTW, defined as ≤ 6 weeks of sickness absence within 12 months after full RTW. Primary and secondary outcomes (e.g., RTW self-efficacy, work ability) were collected at baseline and at 6, 12, 18, and 24 months. Intention-to-treat analyses used logistic regression and growth curve models, complemented by prespecified sensitivity and exploratory moderator analyses.

    Overall, RTW-PIA had no significant effect on achieving SRTW (OR = 1.38 [95% CI 0.89 to 2.12]). Secondary outcomes revealed no significant effects, despite a consistent pattern of slight improvements favoring RTW-PIA. Per-protocol and complete-case sensitivity analyses led to the same conclusion. In diagnostic subgroup sensitivity analyses, employees with recurrent depressive disorders showed significant improvements in several secondary outcomes. Prespecified exploratory moderator analyses suggested potential benefits for employees without a recognized disability degree and for those with low social support at work. After multiplicity adjustment, only recurrent depressive disorder still moderated the treatment effect on work ability.

    On average, RTW-PIA did not significantly improve SRTW or secondary outcomes. Employees without a recognized disability degree, with low social support at work, or with diagnosed recurrent depressive disorders might benefit from RTW-PIA. These hypotheses need to be tested in independent samples. Further research should also focus on the implementation of RTW-PIA.

    DRKS00026232 (prospectively registered on 01/09/2021).
    Mental Health
    Access
    Care/Management
  • The role of sample-specific stressors, social identification, stress mindset and resilience for the well-being of descendants of mentally ill parents: a quasi-experimental cross-sectional study.
    2 weeks ago
    Descendants of mentally ill parents (DMIP) make up about 22% of the population and are 2-13 times more likely to experience mental problems themselves. Preventive health interventions are needed, which should foster protective factors. Unfortunately, little is known about which variables can serve as protective factors for this at-risk group.

    In this quasi-experimental cross-sectional study, we compared DMIP (n = 332) with a control group (n = 90) with mentally healthy parents. We predicted that (1) DMIP report a lower well-being than the control group and that DMIP who experienced more sample-specific stressors report lower well-being, (2) that family identification relates to better well-being but that this relationship is moderated by ambivalent identification and disidentification and (3) that the relationship between sample-specific stressors and well-being is moderated by resilience and stress mindset.

    Analyses show that compared to a control group, DMIP rather have a negative stress-mindset, identify less with their family, show higher disidentification and ambivalent identification with their families and report poorer well-being for most measures. DMIP who experience more sample-specific stressors report lower well-being. Identification with the family positively relates to DMIP's well-being. This relationship was especially strong when ambivalent identification was low (for DMIP but not for the control group). The relationship between the sample-specific stressors and well-being is not moderated by resilience or the stress mindset.

    For preventive health programs, we propose to assess specific stressors and tailor interventions accordingly; to integrate modules which foster identification with the family and reduce ambivalent identification and to test if a stress mindset training benefits DMIP.

    Not applicable.
    Mental Health
    Access
    Care/Management
    Advocacy
  • Infant and Early Childhood Mental Health Training in Psychiatry Residency: National Program Director Perspectives in Canada.
    2 weeks ago
    Infant and early childhood mental health (IECMH) is increasingly recognized as relevant to psychiatric practice; however, its integration into psychiatry training in Canada remains unclear. This study examined how IECMH education is currently delivered within Canadian general psychiatry and child and adolescent psychiatry (CAP) residency programs.

    Program directors (PDs) and associate PDs from all Royal College of Physicians and Surgeons of Canada-accredited General Psychiatry residency programs and CAP subspecialty programs were invited to complete an anonymous survey between August and December 2023. Survey items explored IECMH teaching practices, curricular structure, clinical exposure, perceived resident competence, and barriers and facilitators to implementing formal IECMH curricula.

    Nine PDs participated (four general psychiatry; five CAP). No general psychiatry programs reported mandatory IECMH rotations, and most reported no dedicated IECMH teaching. CAP programs reported greater clinical exposure, with most requiring an IECMH-focused rotation; however, formal didactic teaching remained limited across programs. No programs reported the use of e-learning modules. General psychiatry PDs commonly rated their programs as educating residents in IECMH "not very well," whereas CAP PDs generally selected "moderately well," citing limited faculty expertise as a primary barrier. Conversely, all respondents endorsed IECMH training as "important" or "very important" and expressed strong interest in scalable, self-directed educational approaches.

    IECMH education within Canadian psychiatry residency training is variable and inconsistently structured, despite widespread recognition of its relevance. These findings highlight opportunities to develop feasible, competency-aligned IECMH curricula to strengthen psychiatry training and support developmentally informed clinical practice.
    Mental Health
    Access
    Care/Management
  • The association between eviction moratorium and alcohol use disorder treatment in the United States.
    2 weeks ago
    Alcohol-related morbidity and mortality have risen in recent years while the U.S. confronts a housing affordability crisis. This quasi-experimental event study assessed the association between the end of the federal eviction moratorium and receipt of treatment for alcohol use disorder (AUD) among U.S. residents.

    Using national claims data for June-December 2021, this study calculated state-week measures of AUD treatment. Event study models using Poisson regression estimated how the number of individuals receiving outpatient AUD treatment, prescription medication for AUD, and outpatient treatment for a behavioral health disorder with co-occurring AUD changed in the weeks before and after the federal eviction moratorium expiration in states where evictions resumed (treatment states) compared to states maintaining eviction moratoria (comparison states).

    The state-weekly average number of individuals receiving outpatient AUD treatment was 9.95% greater (Confidence Interval (CI): 2.41%, 18.05%), with about 2440 more individuals receiving an outpatient AUD visit per week, than expected in the 5-16 weeks following the expiration of the federal moratorium in states where evictions resumed.

    Resumption of evictions was associated with greater than expected rates of outpatient AUD treatment . Findings underscore the importance of considering the connection between housing policy and AUD treatment patterns.
    Mental Health
    Access
  • Profound Autism Prevalence and Assessment Practices in a Population-Based Study.
    2 weeks ago
    Profound autism is a proposed subcategory of autism including individuals unable to meet basic daily adaptive needs and requiring 24-hour care. This report describes documented assessment practices and profound autism prevalence derived using different definitions.

    Among 7,084 8-year-old children with autism from a population-based surveillance program in 13 US sites in 2022, we calculated the availability of IQ, verbal status, and adaptive data. We imputed missing data to calculate profound autism prevalence using the "updated" (2025) definition, which includes having 1) either an intellectual quotient (IQ) score <50 OR being nonverbal/minimally verbal AND 2) adaptive functioning significantly below age level (≤70). We compared prevalence using the updated definition to using the "prior" (2021) profound autism definition that did not incorporate adaptive scores, the updated definition with higher IQ score cutoff (≤70), and using only nonverbal/minimally verbal status and adaptive ≤70.

    Among children with autism, 61.1% had IQ data, 74.0% had verbal status data, and 55.9% had adaptive data available. Cognitive data (IQ or verbal status) and adaptive data were available to determine profound autism status for 54.4%. After imputation, updated definition profound autism prevalence was 5.4 (95% CI: 5.1-5.8) and nonprofound autism prevalence was 27.5 (95% CI: 26.8-28.1) per 1,000 8-year-olds in 2022. Of children with autism, 16.5% met the updated profound autism definition and 32.1% met one element of the definition but did not meet full criteria. Prevalence was 33.5% higher using the prior definition, 70.9% higher using the updated definition with higher IQ score cutoff, and 33.3% lower using only nonverbal/minimally verbal status and adaptive ≤70.

    Prevalence of nonprofound autism was higher than profound autism. Adaptive or other assessments underlying the profound autism definition were missing almost half the time. Community evaluation practices and the profound autism definition can evolve to better understand and meet needs of individuals with autism.
    Mental Health
    Access
  • "I see my body the way people see me": A qualitative study on the acceptability and cultural adaptation of the mind.body.voice curriculum for Latina youth.
    2 weeks ago
    Latina adolescents and emerging adults navigate conflicting appearance ideals, balancing the "Latina curvy ideal" with Eurocentric thinness standards that contribute to body dissatisfaction, disordered eating, and emotional distress. Few culturally tailored interventions have been developed or evaluated specifically for Latina youth, particularly in ways that directly center their lived experiences and adaptation priorities. The mind.body.voice (m.b.v.) curriculum is a near-peer-led program integrating cognitive dissonance, contemplative practices, and community action to counter harmful appearance ideals and foster body acceptance. To examine the acceptability and cultural resonance of this approach, we engaged 17 Latina adolescents and young adults (ages 13-22) in virtual focus groups and administered self-report measures of body image, discrimination, acculturation, and ethnic identity. Thematic analysis identified five key domains: 1) body image and identity are shaped by intersecting cultural and societal expectations; 2) appearance biases arise from family influences, cultural norms, media exposure, and internalized pressures; 3) practices such as self-acare, physical activity, mindfulness, and a sense of strength drawn from cultural and familial roots promote body appreciation; 4) empowerment develops through peer support, safe spaces, and shared voice; and 5) culturally congruent, linguistically flexible facilitators enhance engagement. Participants viewed m.b.v. as acceptable and culturally resonant and identified both surface- and deep-structure adaptation priorities to inform future refinement and evaluation.
    Mental Health
    Access