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Early intervention with electrical stimulation reduces neural damage after stroke in non-human primates.3 months agoFor patients experiencing ischemic stroke, acute intervention offers the most critical therapeutic opportunity as it can reduce irreversible tissue injury and improve functional outcomes. However, currently available treatments within the acute window are highly limited and have strict patient selection criteria. Although emerging neuromodulation techniques have been proposed as a treatment for chronic stroke, acute stimulation is rarely studied due to concerns about exacerbating ischemia-induced electrical instability. Here, we demonstrate that acute cortical electrical stimulation, administered one hour post-stroke, provides neuroprotection in non-human primate brains. Using advanced electrophysiology and histology tools, we found that applying continuous theta burst electrical stimulation directly adjacent to the ischemic lesion significantly reduced neural activity in the surrounding tissue, as evidenced by lower electrocorticography signal power and c-Fos expression. This reduced depolarization was accompanied by decreases in neuroinflammation and infarct volume in the sensorimotor cortex. These findings suggest that acute electrical stimulation may serve as a safe and effective early intervention, offering a promising therapeutic strategy to improve outcomes in ischemic stroke.Cardiovascular diseasesCare/Management
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HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.3 months agoCardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression, and play important roles in post-translational modification by catalyzing the deacetylation of key lysine residues in nucleosomal histones, which are closely associated with the occurrence and development of cardiovascular diseases. Recent studies indicate that HDAC inhibitors (HDACis) may represent a new class of drugs for the treatment of cardiovascular diseases by influencing post-translational modifications. In this review, we systematically summarize the mechanism of action of HDACs and HDACis in post-translational modifications related to common cardiovascular diseases, providing new ideas for the treatment of CVD, and explore possible future research directions on the relationship between HDAC and HDACi in post-translational modifications and cardiovascular diseases.Cardiovascular diseasesPolicy
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Modeling Aberrant Angiogenesis in Arteriovenous Malformations Using Endothelial Cells and Organoids for Pharmacological Treatment.3 months agoArteriovenous malformations (AVMs) are congenital vascular anomalies defined by abnormal direct connections between arteries and veins due to their complex structure or endovascular approaches. Pharmacological strategies targeting the underlying molecular mechanisms are thus gaining increasing attention in an effort to determine the mechanism involved in AVM regulation. In this study, we examined 30 human tissue samples, comprising 10 vascular samples, 10 human fibroblasts derived from AVM tissue, and 10 vascular samples derived from healthy individuals. The pharmacological agents thalidomide, U0126, and rapamycin were applied to the isolated endothelial cells (ECs). The pharmacological treatments reduced the proliferation of AVM ECs and downregulated miR-135b-5p, a biomarker associated with AVMs. The expression levels of angiogenesis-related genes, including VEGF, ANG2, FSTL1, and MARCKS, decreased; in comparison, CSPG4, a gene related to capillary networks, was upregulated. Following analysis of these findings, skin samples from 10 AVM patients were reprogrammed into induced pluripotent stem cells (iPSCs) to generate AVM blood vessel organoids. Treatment of these AVM blood vessel organoids with thalidomide, U0126, and rapamycin resulted in a reduction in the expression of the EC markers CD31 and α-SMA. The establishment of AVM blood vessel organoids offers a physiologically relevant in vitro model for disease characterization and drug screening. The authors of future studies should aim to refine this model using advanced techniques, such as microfluidic systems, to more efficiently replicate AVMs' pathology and support the development of personalized therapies.Cardiovascular diseasesPolicy
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The effects of space radiation on the transcriptome of heart right ventricle tissue.3 months agoDeep space represents a challenging environment for human exploration and can be accompanied by harmful health-related risks. We aimed to assess the effect of simplified galactic cosmic ray simulated (simGCRsim) and gamma (γ) ionizing radiation (IR) on transcriptome changes in right ventricular (RV) tissue after a single low dose (0.5 Gy, 500 MeV/nucleon) full body exposure in C57BL/6J male and female mice. In females, no differentially expressed genes (DEGs) and only 2 upregulated genes in males exposed to γ-IR were revealed. In contrast, exposure to simGCRsim-IR resulted in 4 DEGs in females and 371 DEGs in males, suggesting longer-lasting and sex-biased DEGs after simGCRsim-IR. Overrepresentation analysis of DEGs in simGCRsim-IR males revealed significant enrichment in pathways related to muscle contraction, hypertrophic cardiomyopathy, oxytocin release, the regulation of cytoskeleton, and genes associated with Alzheimer's, Huntington's, and Parkinson's diseases. Our results suggested the RV transcriptome exhibits distinct responses after exposure based on both the IR and sex.Cardiovascular diseasesPolicy
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Predictors and Correlates of Depression and Anxiety Symptom Trajectories in a Large Digital Mental Health Provider: Retrospective Analysis of Data From Rula Health.3 months agoDepression and anxiety are highly prevalent and burdensome, yet many individuals, especially those with subclinical symptoms, remain underserved by traditional care models. While digital mental health interventions (DMHIs) have improved access, few integrate high-frequency measurement-based care (MBC) or evaluate outcomes across the full spectrum of symptom severity in real-world settings.
The purpose of this study was to examine the effects of participation in a commercial MBC DMHI, Rula Health, on changes in depression and anxiety over time in both subclinical and clinical patients. We aimed to (1) explore the trajectories of anxiety and depression symptoms and (2) examine the impact of demographics and primary diagnosis on depression and anxiety trajectories.
We retrospectively analyzed longitudinal symptom data from adults receiving therapy through Rula Health, an MBC-based DMHI. Depression, via the Patient Health Questionnaire-9 (PHQ-9), and anxiety symptoms, via the Generalized Anxiety Disorder-7 (GAD-7), were measured before each visit over 12 therapy visits. Linear spline mixed-effects models with a knot placed at 5 visits (based on visual inspection) were used to evaluate symptom trajectories and identify moderators of treatment response, including demographic characteristics and primary diagnosis.
A total of 365,741 adults (mean age 37.03, SD 11.81 years; 238,839/360,388, 66.27% female; 87,758/145,947, 60.13% White) with 2,685,103 therapy visits were included in the sample. Baseline depression (ie, PHQ-9) and anxiety (ie, GAD-7) scores averaged 9.41 (SD 6.61) and 9.45 (SD 5.65), respectively, decreasing to 6.37 (SD 5.83) and 6.50 (SD 5.01) within 12 visits. Depression (β=-0.72, P<.001) and anxiety (β=-0.72, P<.001) symptoms decreased significantly over the first 5 visits, and to a lesser degree over visits 6-12 (depression: β=-0.02, P<.001; anxiety: β=-0.0078, P=.004). Faster improvements over visits 1-5 occurred in younger patients (βPHQ=0.0031, P<.001; βGAD=0.0027, P<.001), and those identifying as Black/African American (βPHQ=-0.089, P<.001; βGAD =-0.042, P<.001), American Indian/Alaska Native (βPHQ=-0.14, P<.001; βGAD=-0.11, P<.001), and Native Hawaiian/Pacific Islander (βPHQ=-0.12, P<.001; βGAD=-0.069, P=.01). Patients with an anxiety (βGAD=-0.071, P<.001) or trauma-related (βGAD=-0.021, P=.03) disorder had faster improvements in GAD-7.
This study contributes to the growing evidence base from commercial DMHIs by demonstrating significant improvements in depression and anxiety symptoms across both clinical and subclinical populations using real-world data from a large, national provider. Symptom reductions were most rapid in the first 5 visits, with continued improvements through session 12, especially among historically underserved groups. These findings highlight Rula Health's ability to deliver early, sustained, and equitable outcomes through an MBC model.Mental HealthAccessCare/ManagementAdvocacy -
Motifs of human high-frequency oscillations structure processing and memory of continuous audiovisual narratives.3 months agoThe discrete events of our narrative experience are organized by the neural substrate that underlies episodic memory. This narrative process is segmented into distinct units by event boundaries, which facilitate a replay process that acts to consolidate each event into a narrative memory. High-frequency oscillations (HFOs) may synchronize neural activity during these processes. We use intracranial recordings from participants viewing and freely recalling a continuous, audiovisual stimulus. We find that hippocampal HFOs increase following event boundaries and hippocampal-cortical coincident HFOs (co-HFOs) occur in cortical regions that underlie event segmentation (inferior parietal, precuneus, lateral occipital, and inferior frontal cortices). Event-specific co-HFO patterns that occur during event viewing reoccur following event boundaries for the subsequent three events and during recall. This is consistent with models that support replay as a mechanism for memory consolidation. Therefore, HFOs may coordinate activity across brain regions that facilitate event segmentation, encode memory of discrete events, and bind representations to assemble memory of a coherent, continuous experience.Mental HealthAccessAdvocacy
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Using epidemiological data to explore the impact of mental health and substance use disorder treatment facilities and family planning clinic availability on pre-exposure prophylaxis use for women in the U.S.3 months agoEnding the HIV epidemic by 2030 is partly dependent on preexposure prophylaxis (PrEP), but usage has been markedly low among women. This study sought to determine if access to mental health and substance use disorder treatment, and family planning clinics have an impact on women's PrEP uptake. Using epidemiological data from publicly available data sources, we employed a difference-in-differences design to quantify the effect of the availability of these facilities on PrEP rate and PrEP-to-need ratio across all 50 states. We found that mental health and substance use disorder treatment had a small effect on PrEP rate for males 0.9% (0.888), but there was no effect on female PrEP outcomes. The availability of family planning clinics was found to be associated with an 8.1% (-0.664) decrease in PrEP rate among females. We concluded that PrEP is not being adequately implemented in mental health and substance use disorder treatment, and family planning clinics, suggesting missed opportunities. These facilities are excellent venues for promoting PrEP adoption as they already reach women susceptible to HIV. The focus should be on embedding PrEP-related care into existing standards of care in these settings to increase PrEP uptake among women who would benefit from PrEP.Mental HealthAccess
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New-Onset Mental Illness Among Gestational Carriers.3 months agoPregnancy is a period of increased vulnerability for psychological well-being. The mental health of gestational carriers is understudied.
To study the association between gestational carriage and new-onset mental illness.
This population-based, retrospective cohort study included all women from the entire province of Ontario, Canada, without known mental illness before pregnancy and who gave birth at greater than 20 weeks' gestation from April 1, 2012, to March 31, 2021. Data were analyzed from September 10, 2024, to May 23, 2025.
Gestational carriers were contrasted with non-gestational carriers who conceived unassisted (comparison 1) or by in vitro fertilization (IVF) (comparison 2).
The main outcome was a diagnosis of new-onset mental illness based on 2 or more outpatient visits or 1 or more emergency department visit or hospital admission and occurring from the estimated date of conception up to a maximum follow-up date of March 31, 2024. Modified Poisson regression-generated incidence rate ratios (IRRs) adjusted for maternal age, income quintile, urban residence, obesity, smoking, parity, and chronic hypertension.
Of 767 406 eligible pregnancies in women (mean [SD] age, 30.5 [5.1] years), 748 732 (97.6%) were by unassisted conception, 17 916 (2.3%) by IVF, and 758 (0.1%) by gestational carriage. Gestational carriers were more likely than unassisted conception and IVF carriers to be parous (91.2% vs 57.9% and 34.1%, respectively), reside in a lower-income area (23.4% vs 21.9% and 12.1%, respectively), and have higher rates of obesity (36.1% vs 17.0% and 17.1%, respectively) and chronic hypertension (3.2% vs 1.6% and 2.9%, respectively). The median (IQR) follow-up was 4.5 (2.3-7.2) years. In comparison 1, new-onset mental illness occurred in 236 gestational carriers (6.9 per 100 person-years) vs 195 022 women with unassisted conception (5.2 per 100 person-years) (adjusted IRR, 1.43; 95% CI, 1.26-1.63). In comparison 2, new-onset mental illness occurred among 236 gestational carriers (6.9 per 100 person-years) and 4704 women receiving IVF (5.0 per 100 person-years) (adjusted IRR, 1.29; 95% CI, 1.13-1.47).
The findings of this cohort study suggest that gestational carriers were more likely to be diagnosed with mental illness during and after pregnancy. Mental health screening, counseling, and provision of support may be particularly important in this population.Mental HealthAccessCare/ManagementAdvocacy -
Teamwork Makes the Dream Work: Who Should Be Managing Athletes on Matters Related to Sleep?3 months agoOptimising sleep health is essential for athlete recovery and performance, but responsibility for managing sleep in high-performance sports is often unclear. Although performance support teams include diverse professionals such as coaches, sport scientists, physiotherapists, sports dietitians, psychologists, and physicians, guidance may be fragmented and inconsistent across training environments and competition schedules. This paper proposes a collaborative multidisciplinary model in which sleep specialists may integrate with existing support staff to deliver unified, evidence-based sleep strategies throughout all phases of athlete preparation. By fostering open communication channels, aligning screening protocols, and coordinating interventions, this model ensures consistent messaging and implementation of sleep initiatives. We also address sleep monitoring via wearable technologies, highlighting device performance and data confidentiality considerations to ensure accurate and ethical use of athlete sleep metrics. Emphasis is placed on creating organisation-wide policies that recognise sleep as an important component to health and performance. Adopting this integrated approach to sleep may enhance overall physical and mental health, reduce injury risk, improve recovery, and ultimately, enhance athletic performance.Mental HealthAccess
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Elite Ice Hockey Players' Well-Being: A Scoping Review.3 months agoAs mental health has gained prominence in recent years, elite ice hockey players have shared their experience of psychological problems, including adverse alcohol use, anxiety, depression, distress, eating disorders, and sleep disturbances. Mental health remains a sensitive issue for ice hockey players, as stigma, a strong hockey culture, lack of mental health literacy, and negative past experiences with seeking help constitute barriers to seeking support. This scoping review aims to identify the psychological factors contributing to elite ice hockey players' well-being. After screening the titles and abstracts of three databases within a 2002-2025 timeframe, a total of 517 articles were retrieved. Seventeen articles targeting ice hockey athletes over 14 years of age competing at an elite level were selected. Three main categories emerged from the included studies: anxiety and depressive symptoms, motivational variables, and coping strategies at different career stages. Factors such as retirement, concussions, social support, parenting style, task-approach goals, and task-oriented behavior were influential components to the well-being and mental health of elite ice hockey players. Using the Lazarus and Folkman model, the identified psychological factors may help athletes and various actors surrounding them to better understand athletes' well-being.Mental HealthAccess