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A chitosan-based multifunctional hydrogel patch improves cardiac health and function by repairing the post-myocardial infarction microenvironment.5 days agoMyocardial infarction (MI) induced ischemia and hypoxia trigger a complex pathological microenvironment characterized by oxidative stress, inflammation, and fibrosis. However, the existing surgical and pharmacological treatments, as well as some tissue engineering techniques, fail to adequately therapy these symptoms, ultimately leading to cardiac dysfunction and poor prognosis. In this study, a multifunctional hydrogel patch composed of chitosan (CS), intrinsically hierarchical silk fibroin (SF) fibers, and reactive oxygen species (ROS) scavenging tannic acid (TA) for cardiac implantation was developed for treating the intricate post-MI microenvironment. This hydrogel not only provides favorable mechanical compliance but also enables sustained release of TA for over 30 days, ensuring long-term ROS scavenging while promoting cardiomyocyte adhesion and survival. In vitro experiments, the hydrogel demonstrates favorable biocompatibility and achieves an effective ROS clearance rate of approximately 80%. In a rat MI model, implantation of the patch reduces inflammatory factor secretion, decreases the myocardial fibrosis area by approximately 25%, and improves the ejection fraction (EF%) by approximately 20% for over 28 days post-MI. Mechanistically, the hydrogel patch synergistically regulates PI3K/Akt, Wnt5a/β-catenin, and TGF-β/Smad5 signaling pathways. In summary, this hydrogel patch offers a promising target strategy for repairing the complex post-MI microenvironment.Cardiovascular diseasesCare/ManagementPolicy
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Clonal hematopoiesis of indeterminate potential and heart disease: What every internist needs to know.5 days agoClonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition defined by somatic mutations in hematopoietic stem cells that result in clonal expansion, without overt hematologic malignancy. It is now recognized as a potent risk factor for atherosclerotic cardiovascular disease, with emerging associations across a broader spectrum of cardiovascular phenotypes, including myocarditis, pericarditis, arrhythmias, valvular heart disease, and heart failure. The authors of this article review the epidemiology, pathophysiology, and management of this condition.Cardiovascular diseasesCare/Management
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The cost of missing cardiovascular data in South Asia and the promise of lifecard.5 days agoCardiovascular diseasesCare/Management
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Stagger-folding leaflet design for improved durability in transcatheter heart valves.5 days agoTranscatheter valve replacement has become the established standard therapy for inoperable, high- and intermediate-risk patients with severe symptomatic aortic stenosis. Leaflet damage due to mechanical loading of the transcatheter valve during crimping process is a significant cause of premature structural valve degeneration. In this study, a novel stagger-folding transcatheter heart valve (THV) was designed to reduce the stress concentration caused by crimping process. The spatial distribution of the leaflets during the crimping process was optimized through axial stagger-folding, effectively mitigating inter-leaflet compression, reducing the risk of leaflet damage, which may enhance the long-term durability of the leaflets. Numerical simulation and multi-objective optimization were employed to optimize the axial displacements of stagger-folding leaflets, and a stagger-folding valve stent was designed based on the optimized design. Compared to conventional normal-folding valve, the novel stagger-folding valve demonstrated significant reductions in damage volume (23.64%), effectively reducing the stress caused by the folding of the valve leaflets. Consequently, the novel THV proposed in this study demonstrated significant potential to mitigate leaflet stress caused by crimping and may enhance valve durability, providing technical support for extending THV service life.Cardiovascular diseasesCare/Management
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Pulse Points: Early Clues and Clinical Pearls in Cervical Artery Dissection.5 days agoCervical artery dissection represents a relevant cause of stroke, predominantly in young adults. The diagnosis can be challenging both clinically and radiographically frequently resulting in underdiagnosis, and management can be controversial. This case study explores a young adult diagnosed with a nontraumatic associated cervical artery dissection and provides an evidence-based overview on diagnostic evaluation, treatment approaches, and outcomes.Cardiovascular diseasesCare/Management
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ERG is a regulator of dynamic and reversible endothelial plasticity.5 days agoEndothelial cells (ECs) orchestrate vascular homeostasis and resilience but can undergo reprogramming into a mesenchymal-like phenotype through an endothelial-to-mesenchymal transition (EndMT). Crucially, EndMT is a linchpin underlying several cardiometabolic diseases, but is almost universally studied as an endpoint. The transcription factor ERG (ETS-related gene) is critical to the maintenance of EC identity and function, yet the dynamic transcriptional and functional consequences of ERG loss on EndMT programs, and whether this can be reversed, has not been explored.
We modeled both acute and chronic ERG loss in human aortic ECs using siRNA knockdown and CRISPR/Cas9-mediated ERG deletion. We profiled temporal changes in chromatin accessibility (ATAC-seq), transcriptomic responses (RNA-seq), and endothelial phenotypes, including migration and barrier integrity. The temporal kinetics of ERG loss and restoration was assessed by comparing stable ERG knockout to transient ERG knockdown and recovery over time. The implications to human disease were deciphered by examining ERG gene regulatory networks in human atherosclerosis and linkage with genetic variation associated with human cardiovascular disease.
Analysis of gene regulatory networks revealed profound and dynamic rewiring of endothelial and mesenchymal transcriptional programs upon loss of ERG. While endothelial identity was rapidly lost by 24 h of ERG knockdown, acquisition of mesenchymal identity, barrier dysfunction, and enhanced cell migration required 72 h to manifest. Loss of ERG was accompanied by a rapid reduction in accessibility of ETS motifs and an extensive gain in open chromatin containing AP1 motifs. Disease-relevant endothelial dysfunction programs were associated with dynamically reorganized transcriptional networks. Importantly, restoration of ERG expression reversed EndMT gene regulatory networks and phenotypes.
Overall, this study highlights the ETS factor, ERG, as an essential transcriptional safeguard of endothelial identity and function, and demonstrates that ERG loss initiates a progressive, yet reversible, EndMT program with EC identity loss preceding a gain of mesenchymal gene regulatory networks and phenotypes. This study establishes loss of ERG as an early initiating event in EndMT and suggests that ERG-targeted therapies may hold promise for promoting endothelial resilience.Cardiovascular diseasesPolicy -
Epigenetic control of ion channels in cardiac fibrosis.5 days agoCardiac 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.Cardiovascular diseasesPolicy
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Delving into the delays: a cross-sectional study on healthcare-seeking following episodes of violence against older adults in Brazil, 2016-2022.5 days agoDelaying 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.Mental HealthAccess -
Women's social care provision in prison has improved but challenges remain: findings from a national survey in England eight years after the 2014 Care Act.5 days agoAt 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.Mental HealthAccessAdvocacy -
Cost-effectiveness and acceptability study of the Unified Protocol for the treatment of emotional disorders in brief groups in primary care services of the Spanish National Health System: a study protocol.5 days agoEmotional 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 (7th August 2024).Mental HealthAccessCare/Management