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Endothelial Shear-Stress-Responsive Gene Adenylate Cyclase 4 Suppresses Atherosclerosis by Inhibiting cAMP/PKA-NF-κB Mediated Vascular Inflammation.2 weeks agoEndothelial dysfunction is critical for the pathogenesis of atherosclerosis, particularly in arterial regions exposed to disturbed flow (DF). ADCY4 (adenylate cyclase 4) catalyzes the production of cAMP, a ubiquitous second messenger that regulates cellular and physiological processes. This study investigated ADCY4 as a shear-stress-responsive gene in ECs for the regulation of vascular endothelial inflammation during atherogenesis.
Integrated analysis of RNA sequencing data sets from human vascular ECs exposed to unidirectional flow or DF, and single-cell RNA-seq data from mouse partial ligation carotid arteries, was performed. ADCY4 expression was quantified in cultured ECs under various flow conditions. Nanoparticles carrying Cdh5 promoter-driven CRISPR-Cas9 Adcy4-specific guide RNA plasmids were used to achieve EC-specific Adcy4 knockout in ApoE-/- mice for atherogenesis studies.
ADCY4 was upregulated in ECs under unidirectional flow but downregulated under DF. We identified that KLF2 directly bound to the ADCY4 promoter and transcriptionally enhanced its expression in human aortic ECs. ADCY4 knockdown in ECs under unidirectional flow increased proinflammatory gene expression and monocyte adhesion, whereas ADCY4 overexpression under DF produced opposite changes. Further studies showed ADCY4 attenuated endothelial inflammation by inhibiting NF-κB signaling. We performed partial carotid ligation in the high-fat diet-fed ApoE-/- mouse atherosclerosis model, demonstrating that EC-specific Adcy4 knockout increased vascular endothelial inflammation and monocyte infiltration, thus promoting atherosclerotic plaque formation. Aggravated atherogenesis was also observed in EC-Adcy4 knockout high-fat diet-fed ApoE-/- mice, with increased atherosclerotic lesions in en face aortas and aortic arches. Finally, semaglutide increased ADCY4 expression in human aortic ECs under DF and reduced vascular endothelial inflammation, monocyte accumulation, and atherosclerotic plaque formation. These beneficial effects were substantially impaired when EC ADCY4 was absent.
ADCY4 regulation of the cAMP/PKA-NF-κB pathway in the endothelium advances our understanding of vascular inflammation in atherogenesis and provides opportunities for therapeutic intervention of atherosclerotic cardiovascular disease.Cardiovascular diseasesPolicy -
Mesoporous Silica-Confined Ruthenium Nanozyme Motors Reprogram Redox-Inflammatory Crosstalk to Suppress Atherosclerosis via NRF2 Nuclear Translocation.2 weeks agoElevated intravascular reactive oxygen species (ROS) and persistent inflammation are defining characteristics of the atherosclerotic microenvironment, making their simultaneous modulation a pivotal challenge in cardiovascular therapy. In response, this study presents a groundbreaking plaque microenvironment regulation strategy enabled by self-propelled nanomotors, referred to as DDMzyme nanomotors, designed specifically for atherosclerosis treatment. These nanomotors autonomously traverse the plaque milieu, catalytically depleting excess hydrogen peroxide and superoxide anions while generating carbon monoxide, a bioactive gas that enhances the targeted accumulation of therapeutic nanoparticles. This synergistic mechanism not only reduces ROS levels during nanomotor movement but also enables additional ROS neutralization through nanozyme payloads delivered directly to the lesion. Functionally, DDMzyme treatment markedly slows atherosclerotic progression by mitigating oxidative stress and promoting cholesterol efflux from macrophages. At the molecular level, DDMzyme activates the NRF2 antioxidant defense pathway by promoting NRF2 dissociation from KEAP1, facilitating its nuclear translocation and the upregulation of downstream cytoprotective genes. This innovation marks a major advancement in precision nanomedicine, introducing a multifunctional, microenvironment-responsive platform that concurrently targets ROS and inflammation in atherosclerosis.Cardiovascular diseasesPolicy
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Vascular smooth muscle cell FTO deletion aggravates atherosclerotic plaque instability by promoting VSMC migration through the N6-methyladenosine modification of the COL3A1 mRNA.2 weeks agoVascular smooth muscle cell (VSMC) migration is the key event in the pathogenesis of atherosclerosis (AS) and plaque instability. Trimethylamine-N-oxide (TMAO) induces VSMC migration to promote the progression of AS. However, the effects of the N6-methyladenosine (m6A) modification on this process remain unclear. Here, TMAO increased total m6A levels in human aortic smooth muscle cells (HASMCs) and decreased fat mass and obesity-associated protein (FTO) and YTH domain-containing family protein 2 (YTHDF2) protein expression. FTO or YTHDF2 overexpression significantly inhibited HASMC migration induced by TMAO. Mechanistically, the COL3A1 gene was shown to be critical for the regulation of HASMC migration by FTO or YTHDF2. Furthermore, methylated RNA immunoprecipitation and RNA stability assays demonstrated that FTO bound to the COL3A1 mRNA and altered its m6A modification, resulting in its decay. In vivo, VSMC-specific FTO or YTHDF2 deletion aggravated AS and plaque instability, whereas adeno-associated virus serotype 9 (AAV9)-mediated VSMC-specific YTHDF2 overexpression or COL3A1 knockdown exerted protective effects on AS and/or plaque instability. Notably, VSMC-specific FTO deletion promoted VSMC migration in atherosclerotic lesions in ApoE-/- AS model mice, whereas VSMC-specific YTHDF2 overexpression had the opposite effect. Overall, the in vitro and in vivo evidence highlights the critical role of the FTO/YTHDF2/COL3A1 axis in VSMC migration, AS, and plaque instability, suggesting that targeting the FTO/YTHDF2/COL3A1 axis in VSMCs may be a novel and promising therapeutic strategy for the treatment and prevention of AS and plaque instability.Cardiovascular diseasesPolicy
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Patient-Reported Experiences of Abortion Travel.2 weeks agoIllinois is an abortion hub serving a high volume of patients who travel from midwestern and southern states for abortion care. To sustain access to quality services and reduce health care barriers, research is needed to understand the experiences of abortion travelers.
To explore the experiences of out-of-state individuals who travel to central and southern Illinois to receive abortion care.
This qualitative study used purposeful sampling to recruit 208 participants at 2 abortion clinics between November 2024 and August 2025. Participants completed the study at the time of recruitment.
Participants traveled for abortion care based on their state of residence.
Using reflexive thematic analysis, both the experiences of out-of-state abortion travelers in central and southern Illinois and the need for reduction in access barriers for those traveling for abortion were examined.
In this qualitative study of 208 abortion seekers who successfully traveled to Illinois, 128 (61.54%) self-identified as Black, 50 (24.03%) non-Hispanic White, and 30 (14.42%) as women from additional minoritized racial and ethnic groups. Participants' age ranged from 18 to 45 years. All lived in midwestern or southern states. Participants were interviewed in a private room at the clinic between November 2024 and August 2025. Participants discussed structural, logistical, and emotional challenges. Yet, they described abortion traveling as necessary because of the abortion ban and misinformation, which contributed to increased medical distrust. Medical distrust was already rooted in some participants' previous experiences of receiving biased reproductive care, and for Black women, it worsened because of historical mistreatment and discrimination. Increased medical distrust likely drove people to travel for abortion care.
These findings call for enhanced coordination of care with centralized trusted resources, equitable distribution of funding, mental health support, and attention to reduce biased care for Black women. The results also highlight the need to develop strategies to combat misinformation and increase advocacy efforts to reduce abortion stigma.Mental HealthAccessCare/ManagementAdvocacy -
"Walking While Black": Impacts of Inequities in Nature Access and Belongingness.2 weeks agoAs a framework for understanding inequities in nature access andbelongingness among Black Americans, this review examines the historical and public health significance of "Walking While Black." By tracingthe colloquial evolution of "Walking While Black," contemporary experiences within a broader history of racialized surveillance and exclusionare positioned.
Recent research indicates that inequities in nature access extend beyond the physical availability of parks and green spaces to include safety, inclusion, and belongingness. Historical and contemporary forms of racial exclusion have limited outdoor engagement for many Black Americans. These inequities are associated with reduced physical activity, chronic stress, anxiety, hypervigilance, environmental injustice, and diminished opportunities for social connection and community engagement. "Walking While Black" reflects the enduring racialization of mobility and presence in public and natural spaces. The resulting barriers to nature access and belongingness contribute to physical, mental, emotional, and social health disparities among Black Americans. Achieving environmental and health equity requires both expanding access to green spaces and creating environments where Black individuals can safely and freely exist without fear, suspicion, or exclusion.Mental HealthAccessAdvocacy -
Effects of insomnia-focused psychological and behavioral interventions on depressive symptoms in children and adolescents: a systematic review and meta-analysis.2 weeks agoPsychological and behavioral interventions for insomnia are increasingly recognized as promising approaches not only to improve sleep but also to influence mental health outcomes in children and adolescents. This systematic review and meta-analysis examined the effects of insomnia-focused psychological and behavioral interventions on depressive symptoms, with particular attention to potential across selective and indicated prevention as well as adjunctive treatment contexts. A comprehensive literature search was conducted in PubMed/MEDLINE, PsycINFO, the Cochrane Library, and major Chinese databases (CNKI, Wanfang) from inception to December 30, 2025. Randomized controlled trials comparing psychological or behavioral insomnia interventions with control conditions and reporting changes in depressive symptoms in children and adolescents were included. Random-effects meta-analyses, meta-regression analyses, and within-arm standardized mean change analyses were performed. Eight studies comprising 904 participants (mean age=13.46 years) were identified. Across all studies, depressive symptoms improved from baseline to post-intervention, with a significant overall benefit of insomnia-focused interventions compared with control conditions (SMD=0.238, 95% CI=0.088-0.387, p=0.0019). Within-arm analyses indicated that effects in passive-comparator studies reflected genuine intervention benefit rather than spontaneous remission. Subgroup analyses showed no significant moderation by delivery format or setting, including digital interventions. The high intervention completion rate across trials (87%) supports the potential of insomnia as an indirect, less-stigmatizing entry point for depression prevention in children and adolescents - consistent with frameworks proposing that targeting comorbid, causally linked conditions may reduce depressive symptoms while lowering barriers to engagement. Integrating evidence-based insomnia interventions into clinical, school-based, and digital settings could substantially extend the reach of early mental health strategies.Mental HealthAccessCare/Management
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Growing Suicides in India: Looming Disaster among the World's Largest Population.2 weeks agoThis comment aims to comprehensively analyse the alarming increase in suicide rates in India, emphasizing demographic variations, contributory factors, and existing preventive measures. The study also explores the effectiveness of the National Suicide Prevention Strategy (NSPS), Mental Healthcare Act (MHCA), and other initiatives in addressing this public health crisis. This comment concludes that while India has taken crucial steps in formulating suicide prevention strategies, effective implementation remains a challenge. Recommendations include increasing access to mental health support, enhancing telepsychiatry services, and promoting responsible media coverage. Collaboration between the health and education sectors, along with targeted prevention tactics for high-risk groups, is essential to curb the growing suicide crisis in India. The study underscores the urgency of a holistic and collaborative approach to mental health awareness and intervention.Mental HealthAccess
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MHSRS: Military Officers' Experiences With Soldiers' Suicidality.2 weeks agoA historical comparison by Smith et al (2023) found that current U.S. Army soldiers are at greater risk for suicide compared to civilians. U.S. Army Behavioral Health Officers (BHOs) and Commanders (CDRs) are closely involved in the care of soldiers with suicide-related incidents; however, little is known about their observations of predictors of suicidality, or their views of barriers and facilitators to care for suicidal soldiers. Well-established theoretical frameworks (Interpersonal Theory of Suicide, Psychache, and Military Transition Theory), have been shown to better predict suicidality over psychiatric diagnoses. This study sought to examine BHOs' and CDRs' views on the observance and rating the importance of these theories, nominating a soldier with reported suicide-related incident. Additionally, these officers were asked to identify barriers and facilitators to delivering care.
Current and former BHOs and CDRs were emailed surveys using convenience and snowball sampling. Participants identified soldiers with suicide-related incidents, rated the importance of theory constructs in predicting or explaining incidents, and potential barriers and facilitators to care were assessed. Descriptives, chi-square tests, and independent sample t-tests were performed with Stata/SE 17.0.
Fifty BHOs and 48 CDRs participated. Officers endorsed the importance of theory constructs predicting suicidality but described having limited information to assess them. BHOs tended to endorse the importance of interpersonal theory of suicide perceived burdensomeness and psychache more highly than CDRs, likely related to their clinical experience. Barriers to care: Stigma specific to receiving BH care was the most important barrier identified. Soldiers' fear of negative career impacts and long waiting lists for BH were also barriers. Facilitators to care: Engaged peers, leadership, and family support were leading facilitators.
The objective of this study use the recollection of officers to assess their knowledge and utilization of theories. Army officers responsible for implementing suicide prevention strategies and postvention efforts believed that theory constructs were observed at the time of incidents. Utilization of these theories could enhance suicide prevention and intervention efforts, future training and policy.Mental HealthAccessCare/ManagementAdvocacy -
Post-Injury General Medical Care Usage for Military Health System Beneficiaries Living in United States Primary Care Deserts and Overseas.2 weeks agoLimited healthcare access can adversely affect military readiness and the health of active duty service members (ADSM) and their families, particularly following serious injury. Approximately half of U.S. military installations are overseas, or in federally designated primary care (PC) Health Professional Shortage Areas, or "PC deserts," characterized by limited provider availability and longer distances to care, which may impact post-injury care. The study objective was to assess the impact of living in a U.S. PC desert or overseas compared to a U.S. non-desert on the rate of general medical (GM) non-surgical, non-mental health care encounters during the year following a serious injury among ADSM, spouses, and children.
A retrospective cohort study of Military Health System (MHS) data from FY 2005-2016 identified seriously injured ADSM, spouses, and children using ICD-9 codes for concussion, fractures, post-traumatic stress disorder, blindness, burns, shrapnel, and other traumatic injuries. Negative binomial regression estimated post-injury GM encounter rates comparing beneficiaries assigned to installations in PC deserts or overseas with those in U.S. non-desert areas, adjusting for age, sex, ADSM race, and rank.
Among 545,611 injured beneficiaries (301,846 ADSM, 77,813 spouses, 75,952 children), residence in PC deserts was associated with increased outpatient civilian care and decreased outpatient military treatment facility (MTF) care. In PC deserts, inpatient care was decreased for spouses and children but increased for ADSM compared to U.S. non-deserts. Overseas outpatient care was decreased for all beneficiary categories, as was inpatient care for dependents, although inpatient care for ADSM was increased overseas. In PC deserts, civilian care was generally increased, whereas overseas, care at military facilities was increased.
These findings highlight geographic disparities in healthcare utilization among MHS beneficiaries and underscore the importance of considering location-based access challenges in military medical resource planning and policy.Mental HealthAccessCare/ManagementAdvocacy -
Shifting From Morning to Afternoon Physical Training Is Associated With Improved Sleep Health, Morale, and Operational Readiness in Soldiers.2 weeks agoSufficient sleep is critical to optimal physical, cognitive, and mental health, yet two-thirds of U.S. Army Soldiers chronically obtain less than the daily recommended 7 or more hours of sleep. Early morning physical training (PT) could impede the amount and quality of sleep soldiers obtain, thereby impairing overall health and operational readiness.
This study examined the effects of a behavioral intervention, in which PT was shifted from morning to afternoon (at 2:00 PM), on measures of sleep health, mental health, and morale. Thirty-seven active-duty soldiers completed surveys along with cognitive and physical testing at 2 timepoints: after ∼30 days following a morning PT schedule (6:30 AM) and again after ∼30 days of an afternoon PT schedule.
Although total sleep duration per 24 hours was not found to differ between PT schedules (t28 = -0.31, P = .38), measures related to general sleep health were significantly improved. Specifically, sleep quality (Pittsburg Sleep Quality Index; t33 = 2.60, P < .01), daytime sleepiness (Epworth Sleepiness Scale; t33 = 2.88, P < .01), and insomnia symptomology (Insomnia Severity Scale; t33 = 2.14, P = .02) were all significantly improved after shifting to afternoon PT. Furthermore, although subjective mental health metrics of stress and anxiety remained similar (low to moderate) between PT schedules, morale was significantly improved following an afternoon PT schedule (t34 = -2.04, P = .03).
These findings indicate that a simple intervention of shifting PT timing from early morning to afternoon to allow for more opportunity to sleep, supported by leadership, can lead to improved sleep health and morale, which can improve overall operational readiness for active-duty service members.Mental HealthAccessAdvocacy