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Gut microbiota-regulated cell death: a review on pyroptosis, ferroptosis, and related mechanisms.3 weeks agoThe intestinal microbiota has emerged as a crucial regulator of host physiological functions, significantly influencing various forms of regulated cell death (RCD). Among these, pyroptosis and ferroptosis play pivotal roles in immune regulation, metabolic homeostasis, and disease progression. The gut microbiota modulates these cell-death pathways through microbial metabolites, inflammatory signaling, oxidative stress, and immune-cell polarization, thereby affecting intestinal disorders, metabolic diseases, cardiovascular diseases, and neurodegenerative diseases. However, current evidence remains fragmented across individual cell-death pathways, and direct microbiota-mediated regulation is often not clearly distinguished from indirect associations arising from barrier dysfunction, inflammation, or metabolic remodeling. This review critically synthesizes the regulatory networks linking the gut microbiota to pyroptosis, ferroptosis, and related cell-death mechanisms. Throughout, we use RCD as the umbrella term for genetically encoded death programs and reserve programmed cell death (PCD) for its physiological, developmental subset, and we grade the supporting evidence at four levels: direct microbial regulation of the death machinery, experimentally demonstrated microbiota-dependent regulation, indirect effects mediated by barrier dysfunction or inflammation, and purely observational association. By integrating recent findings, we discuss the potential and limitations of therapeutic strategies targeting microbiota-regulated cell death. This synthesis provides a framework for defining current evidence gaps and guiding future mechanistic and translational studies.Cardiovascular diseasesPolicy
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Epigallocatechin-3-gallate Modulates Hyperglycemia-Triggered Macrophage Autophagy Through miR-204-5p Suppression: Implication for Acute Cardiometabloic Injury.3 weeks agoEpigallocatechin-3-gallate (EGCG) possess many biological properties. Autophagy and inflammation interact to cause cardiovascular diseases, and diabetic cardiovascular diseases; hyperglycemia- and hyperinsulinemia-induced microRNA reduction in the diabetic heart contribute to poor survival and increased infarct size in diabetic myocardial ischemia/reperfusion. However, whether EGCG affects macrophage autophagy and microRNA 204-5p (miR-204-5p) regulation under hyperglycemic conditions remain unclear. In this report, we investigated the effects of EGCG on the molecular regulatory mechanisms of miR-204-5p in LC3B macrophage autophagy under hyperglycemic stimulation conditions. Reverse transcription and real-time quantitative polymerase chain reaction, western blots, and luciferase activity assay were performed. Macrophages were cultured with 5.5 mM (low glucose) and 25 mM (high glucose) for hyperglycemia stimulation, and hyperglycemia was induced for 1 hour. EGCG attenuated cytoplasmic miR-204-5p levels under hyperglycemia stress in time-course and concentration dependent manners. Hyperglycemic treat-EGCG augmented the macrophage autophagy marker LCB mRNA by under hyperglycemia stress in a time-dependent manner significantly. Treatment with EGCG (10-5 M) or rapamycin or mutant miR-204-5p significantly augmented the LC3B protein expression through the suppressed miR-204-5p level in mouse macrophage cultures under high glucose (25 mM) stimulation at 6 hours. By luciferase activity assay, EGCG combined mutant miR-204-5p reduced LC3B binding activity under hyperglycemia stress. Taken together, EGCG regulates LC3B presentation under hyperglycemia stress by mediating the miR-204-5p under mimicking cardiometabolic injury. This study demonstrated that EGCG upregulated LC3B to suppress miR-204-5p expression in hyperglycemia-stimulated macrophage cultures. The results imply that EGCG is potentially effective for preventing hyperglycemia related cardiovascular diseases.Cardiovascular diseasesPolicy
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Mortality patterns related to stroke and dementia among older adults in the U. S.: a CDC WONDER analysis from 1999 to 2024.3 weeks agoBlood flow impairment due to stroke substantially causes neuronal loss, ultimately leading to cognitive decline. Dementia is a progressive neurocognitive disorder that represents a major public health challenge worldwide.
We analyzed stroke and dementia related mortality trends among older adults using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2024. Age-Adjusted Mortality Rates (AAMRs) per 100,000 were calculated and categorized by demographics and region. Joinpoint regression was used to estimate Annual Percent Change (APC) and Average Annual Percent Change (AAPC).
A total of 965,793 deaths due to stroke and dementia among older adults aged ≥65 years were recorded. Among the subgroups of dementia, unspecified dementia reported the greatest mortality. The AAMR observed a steep incline from 69.34 in 1999 to 99.25 in 2024. Older females observed higher overall AAMR than older males. Racially, Non-Hispanic Black population had the highest overall AAMR. Regionally, the highest overall AAMR was recorded by the Southern U. S. Despite COVID-19, the post pandemic era observed increasing mortality.
Our cohort exhibited a rise in mortality rates among elderly with stroke and dementia, underscoring the need for preventive strategies, and targeted interventions in vulnerable populations and regions.Cardiovascular diseasesPolicy -
Employee Perceptions of a Clinical Department's Response to the COVID-19 Pandemic.3 weeks agoDuring the outbreak of the COVID-19 pandemic in the United States in 2020, hospital systems faced significant challenges, including high patient demand, a lack of resources, and the rapidly evolving safety mandates that necessitated new clinical protocols. However, the perceptions of healthcare workers regarding the effectiveness of their departments and management approaches have not been well described.
Thirty semistructured interviews were conducted with healthcare workers in a single clinical department at a pediatric tertiary care hospital in October 2020, 6 months after the issuance of the state-of-emergency order for the pandemic. Thematic analysis was used to identify and differentiate key insights related to both effective and ineffective practice changes that emerged during this period.
The transition to remote work during the COVID-19 pandemic was marked by challenges related to technological adaptation and data security, mitigated in part by proactive logistical support, incorporation of department-wide virtual meetings, and a dedicated task force. Changes in healthcare access practices were necessitated by rapidly evolving guidelines, resulting in innovative patient care approaches. Nevertheless, the blurred boundaries between personal and professional lives exacerbated stress and burnout among personnel, necessitating leadership intervention to reaffirm work-time boundaries and promote strategic task prioritization.
Instituting consistent channels of communication is instrumental in offering support and disseminating information to employees. Actively maintaining boundaries and prioritizing work-life balance prevents negative impacts on employee mental health. Healthcare entities should invest in strengthening workplace culture and ensuring that these competencies are integrated into practice beyond crisis situations.Mental HealthAccessCare/Management -
Altered serum interleukin-4 and monocyte chemoattractant protein-3 levels are associated with generalized anxiety disorder: a case-control study.3 weeks agoGeneralized Anxiety Disorder (GAD) is a long-term mental health condition often associated with immune system dysregulation. While pro-inflammatory and anti-inflammatory cytokines are known to influence neuroinflammation, their specific roles in GAD remain less understood. This study investigates the relationship between serum levels of IL-4 and MCP-3 and GAD in a Bangladeshi population. This case-control study included 44 patients with GAD and 44 healthy controls (HCs). Participants were examined using the GAD-7 scale. Serum IL-4 and MCP-3 levels were measured using ELISA. Data were analyzed using t-tests, Spearman's correlation, and Receiver Operating Characteristic (ROC) curve analysis to assess diagnostic performance. GAD patients had significantly lower serum IL-4 levels (11.82 ± 10.91 pg/mL) and higher MCP-3 levels (57.80 ± 19.85 pg/mL) compared to HCs (IL-4: 24.51 ± 15.36 pg/mL; MCP-3: 34.01 ± 15.75 pg/mL; p < 0.001). IL-4 levels showed a significant negative correlation with GAD-7 scores (r = -0.496, p < 0.001), while MCP-3 showed a positive correlation (r = 0.544, p < 0.001). ROC analysis indicated that MCP-3 had higher diagnostic accuracy (AUC = 0.848, sensitivity = 87.6%, specificity = 84.3%) compared to IL-4 (AUC = 0.782, sensitivity = 80.2%, specificity = 78.5%). Moreover, decreased IL-4 and elevated MCP-3 levels were found to be significantly associated with GAD severity, suggesting an immune imbalance. These cytokines may serve as promising diagnostic biomarkers and therapeutic targets for GAD. Further longitudinal studies are recommended to investigate this causal relationship and its underlying mechanisms.Mental HealthAccessAdvocacy
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Aging in the Himalayas: Assessing the Quality of Life and Needs of Senior Citizens in Lomanthang, Nepal.3 weeks agoThe elderly population in Lomanthang Rural Municipality, Mustang, accounts for 13% of the total population, significantly exceeding the national average of 6.93%. We conducted a cross-sectional survey with narrative components designed to comprehensively assess their healthcare needs and Quality of Life (QoL). We surveyed all 188 older adults in the region. Functional assessment showed over 90% of participants managed daily activities independently. 58.51% reported uncomfortable movement within their homes due to architectural barriers such as stairs and unfriendly toilets. Social assessment revealed that 62.23% lived with their children, whereas 37.77% lived without children. Physical health findings showed widespread musculoskeletal pain (84.57%) and sight impairments (65.42%). 8.51% of respondents were hypertensive, while 5.85% had signs of malnutrition (upper arm circumference <21 cm). Mental health and well-being assessment revealed that 71.81% had forgetfulness and 5.85% had suspected cognitive impairment. Furthermore, we found that their happiness lies in their relationship with family and good friends. Overall, 20.20% were classified as requiring professional care support. This research underscored the need for interventions to provide timely physical check-ups and improve easy access to basic healthcare services and social connections through FCHVs- an effective community-based approach to enhancing their quality of life and addressing healthcare needs.Mental HealthAccess
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An Item-Level Analysis of Patient Health Questionnaire (PHQ-9) Among Adolescents in Primary Care.3 weeks agoAdolescents are at increased risk for meeting diagnostic criteria for depression and chronic impairments in functioning. Despite the potential consequences, adolescents have poor access to mental health treatment. To increase access, professional organizations recommend pediatricians regularly screen for symptoms of depression with the goal of identifying, preventing, and treating depression. The Patient Health Questionnaire (PHQ-9) has become a frequently used screener in primary care due to its brevity and well-established psychometric properties among both adults and adolescents. The present study aims to expand on this research by examining the quality of individual PHQ-9 items in an ecologically valid sample of adolescents screened for depression during their well-child exams.
Participants include 11,058 adolescents who were screened using the PHQ-9 at a primary care clinic.
This retrospective chart review study demonstrated that all nine items discriminate moderate to severe depression severity. The PHQ-9 provides the most information about two standard deviations above the mean, indicating more error when measuring mild levels of depression. Some PHQ-9 items function best at lower levels of depression, whereas others function best at higher levels of depression. Four of the PHQ-9 items do not show evidence of equal interval response options.
Individual symptoms of depression endorsed by adolescents should be considered when interpreting the overall depression scores. The clinical implications related to ultra-brief depression screening and suicidal ideation screening are discussed as well as limitations and future directions.Mental HealthAccessCare/Management -
Implementing the Empowering Better End of life Dementia Care (EMBED-Care) Framework to improve palliative dementia care in care homes: A feasibility evaluation.3 weeks agoCare homes are the main provider of palliative care for people living with dementia. In the UK around 70% of care homes are residential, with no onsite medical or nursing staff to manage residents' complex needs. eHealth interventions can support holistic care delivery in this context; however, adoption in care homes has been limited. Innovative approaches grounded in implementation science are required to encourage uptake. This study aimed to assess the feasibility of a theoretically informed implementation plan for the EMBED-Care Framework, an eHealth intervention delivered via a mobile app to support holistic assessment and decision-making for people living with dementia in care homes.
An embedded mixed-methods feasibility study was conducted in two residential homes. Qualitative data included non-participant observations, focus groups and semi-structured interviews with staff, analysed using codebook thematic analysis informed by Normalisation Process Theory. Quantitative data comprised app-usage metrics, analysed descriptively. Patient and public involvement informed the study design and conduct.
Twenty staff across two care homes used the intervention with 26 residents. Although some uptake was observed, usage data indicated that the Framework was largely not used as intended. Whilst care staff acknowledged its potential benefit, they faced substantial practical challenges to its use related to workload and a sense it was duplicating existing care processes. These issues led to negative appraisals of its impact and compromised staff engagement.
Feasibility evaluation enabled rapid identification of barriers and refinement of implementation strategies. Iterative revisions to strategies related to providing further staff support, including a more tailored approach to training, and additional reminders to use the Framework. The Framework itself also requires adaptation to improve 'fit' in the care home context. Further collaboration on the revised strategies with people living with dementia and their family carers is required.Mental HealthAccessCare/Management -
Mandates are not enough: placement provider and systems factors that drive ambulatory healthcare use for children in foster care.3 weeks agoIn the United States, children are mandated to receive healthcare when they enter foster care and regularly thereafter; states may require more frequent visits. Despite regulations and public insurance to support access to healthcare for young people in foster care, health outcomes for this population remain poor. This study seeks to understand the extent to which caregiver/placement characteristics, child characteristics, and an information-sharing intervention are associated with receipt of mandated healthcare visits for youth in foster care, which may help the field to better understand why health disparities persist for youth in foster care.
This retrospective observational study uses administrative data from the child welfare system linked to the electronic health record at a freestanding children's hospital that is contracted to provide mandated healthcare visits for children entering foster care or experiencing placement changes. All children (0-21 years) in foster care for at least one day in a licensed, kinship, group home, or independent living placement in a single Ohio county between 2012 and 2025 (N = 24,904 placements for N = 10,729 youth) were included. Cross-classified multilevel logistic models predicted mandated visits within placements and accounted for the cross-classification of children within families of origin, placement providers, and the clustering of repeated observations within children.
The odds of completing a mandated visit was 73%. Placement providers accounted for the largest amount of variance in receipt of mandated care (44% in the adjusted model). Placement in settings other than licensed foster homes (i.e., kinship, group home, independent living) significantly reduced the likelihood of visits. While prior placement providers' experience was generally beneficial, it did not increase visit completion among those in kinship care. Across child characteristics (e.g., age in years, sex, race, ethnicity, number of unique medical diagnoses, number of unique mental health diagnoses), mental health diagnoses were significantly and meaningfully associated with completed visits. Finally, information sharing between healthcare and child welfare systems was associated with a greater likelihood of completing mandated visits (OR = 1.50).
These results indicate that simply mandating visits is insufficient to ensure their completion. Caregiver factors, information sharing between healthcare and child welfare systems, and children's needs likely all represent mechanisms by which the healthcare and child welfare systems can increase mandated healthcare use.Mental HealthAccessCare/Management -
Perceived impact of a homeless shelter-based art program on stress, social connection, and emotional regulation: a mixed-methods pilot study.3 weeks agoIndividuals experiencing homelessness often experience chronically high levels of stress that adds an additional challenge to their lives. Barriers such as stigma, distrust, and accessibility limit engagement with traditional mental health services. Art creation may offer an accessible, non-clinical complement to existing supports by creating space for emotional expression, reflection, and self-directed coping. This pilot study examined the feasibility, acceptability, and perceived impact of an art creation program for guests of a homeless shelter. Utilizing a mixed-methods approach, the program effects were evaluated based on 1) observations from session facilitators, 2) semi-structured interviews with shelter staff and leadership, and 3) pre and post-session participant surveys. Thematic analysis of facilitator reflections identified three primary themes: (1) art as a welcomed respite from institutional monotony, (2) structured art creation as a space for self-reflection and emotional expression, and (3) art as a catalyst for social connection. The third theme included subthemes highlighting how art-centered conversations fostered connection through shared experiences and supported vulnerability. Shelter staff reported increased spontaneous use of art materials outside structured sessions and perceived reductions in interpersonal conflict, suggesting broader cultural integration of art as a coping tool. Participant surveys demonstrated repeat participation, reduction in stress, and that many participants utilized skills gained during the sessions in their everyday life. This pilot study suggests that simple art creation sessions are well received by shelter guests and are associated with perceived stress reduction and increased usage of art as a coping strategy. Art-based interventions may represent a scalable, low-cost approach to complement existing behavioral health supports in shelter-based settings.Mental HealthAccessCare/ManagementPolicy