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Does the obesity paradox truly exist? A study on the relationship between different degrees of obesity and stroke incidence and mortality based on the UK Biobank.3 weeks agoObesity has been associated with increased incidence and severity of various cardiovascular risk factors, as well as an elevated risk of stroke. However, the evidence of its effect on outcomes in stroke patients has been equivocal. Previous studies have documented the obesity paradox in stroke, characterized by a negative correlation between BMI and stroke mortality. To address the limitations of relying solely on BMI in previous investigations, notably the documented obesity paradox linking BMI to stroke mortality, our study incorporates additional obesity metrics beyond BMI. We aimed to comprehensively evaluate the relationship between obesity and stroke outcomes, thereby providing a more holistic understanding of their association.
The present study included 502,128 participants from the UK Biobank database. Cox proportional hazard models were performed to determine the associations of indicators, including BMI, WC, WHR, WHtR and BFP with the incidence and mortality of stroke.
Increased BMI was associated with elevated stroke incidence and mortality, with the lowest risk observed in the BMI range of 18-24 kg/m². Both lower BMI (17≤BMI<18.5 kg/m²) and higher BMI (BMI≥25 kg/m²) were linked to higher incidence and mortality of stroke. In contrast, other obesity-related indicators (WC, WHR, WHtR and BFP) exhibited more pronounced linear relationships with the incidence of stroke, all-cause mortality in the total population, stroke mortality in the total population and all-cause mortality in stroke patients. However, no significant differences were found in stroke-specific mortality among underweight, normal weight, overweight and obese groups in stroke patients across various obesity indicators, suggesting no obvious association between obesity and stroke-specific mortality in stroke patients under the current definitions and adjustments in this study. Notably, stroke severity, acute care, and complications were not available in the analysis, and residual confounding from these unmeasured factors cannot be ruled out. Furthermore, our analyses on the relationships between several obesity subtypes with different metabolic health statuses and stroke incidence and mortality revealed that, regardless of normal weight or not, individuals with metabolic abnormalities had significantly higher incidence and mortality of stroke compared to those with normal metabolism. This highlights the importance of metabolic status in the onset and prognosis of stroke.
Our findings demonstrate that stroke-specific mortality in stroke patients was not associated with obesity severity when assessed using multiple obesity indicators including BMI, WC, WHR, WHtR and BFP. This is inconsistent with previous observations of the obesity paradox. Meanwhile, the observation that individuals with metabolic abnormalities exhibit significantly higher stroke incidence and mortality compared to those with normal metabolism further confirms the adverse impact of metabolic disturbances on stroke risk and prognosis, underscoring the pivotal role of metabolic health in stroke management.Cardiovascular diseasesCare/Management -
Molecular phenotyping with 18F-FDG and 18F-FAPI PET/CT: advancing risk stratification in in-stent restenosis.3 weeks agoTo investigate the potential of 18F-FDG and 18F-FAPI PET/CT for characterizing the pathophysiological heterogeneity of in-stent stenosis (ISR) and to assess their ability to differentiate between its clinically subtypes.
This prospective study enrolled participants with ISR selected from a cohort registry between December 2024 to August 2025, which was categorized into rapid recurrent ISR (R-ISR) and ordinary ISR (O-ISR) based on recurrence time interval. For vessel-level analysis, coronary arteries without intervention served as control. All participants underwent both 18F-FDG and 18F-FAPI PET/CT to assess coronary uptake and evaluated the performance of maximum standardized uptake value (SUVmax) and maximum target-to-background ratio (TBRmax) in differentiating ISR from control vessels, as well as R-ISR from O-ISR. All patients were followed-up. The primary endpoint was a composite of cardiovascular death, target-vessel-related myocardial infarction, or target-vessel-related revascularization. Differences in the diagnostic performance of PET parameters and associations with outcomes were assessed.
Thirty-one participants and 84 vessels were included. ISR vessels (n = 39) demonstrated higher uptake in 18F-FDG and 18F-FAPI than control (n = 45). R-ISR exhibited higher uptake compared to O-ISR on both patient-level (TBRmax: 18F-FAPI, 4.10 ± 1.41 vs. 1.75 ± 0.50; 18F-FDG, 1.18 ± 0.32 vs. 0.86 ± 0.19) and vessel-level (TBRmax: 18F-FAPI, 4.07 ± 1.29 vs. 1.65 ± 0.50; 18F-FDG, 1.16 ± 0.31 vs. 0.90 ± 0.28) (all P ≤ 0.01). 18F-FAPI showed better diagnostic efficacy compared to 18F-FDG (AUC of TBRmax: 0.97 [0.92-1.00] vs. 0.75 [0.58-0.91], P = 0.01]. Six of 31 participants within R-ISR group reached the endpoint. Baseline PET uptake was associated with subsequent outcome (18F-FAPI SUVmax, HR, 2.28 [95%CI: 1.25-5.09], P = 0.02; 18F-FDG SUVmax, HR, 33.2 [95%CI: 4.93-509], P = 0.002).
18F-FAPI and 18F-FDG PET/CT reveals the molecular heterogeneity of ISR, with 18F-FAPI better identifying the rapid-recurrence subtype for advancing risk stratification.
NCT05437965. Registered 24 June 2022.Cardiovascular diseasesCare/Management -
USP43-mediated deubiquitination of SLC7A11 protects against LPS-induced acute lung injury by inhibiting ferroptosis.3 weeks agoAcute lung injury (ALI) is a common inflammatory pulmonary disorder, with increasing evidence implicating ferroptosis as a critical type of cell death in its pathogenesis. Ubiquitin-specific protease 43 (USP43) is an important deubiquitinating enzyme that plays a significant role in both inflammation and ferroptosis regulation. In this study, we mainly analysed whether USP43 could participate in the process of ALI by regulating the ferroptosis process, and clarified its molecular mechanism.
To investigate the functional role of USP43 in ALI, Usp43 knockout mice, USP43 knockdown and overexpressed human bronchial epithelial BEAS-2B cells and mouse alveolar type II epithelial MLE12 cells were treated with lipopolysaccharide (LPS) in vivo and in vitro. Subsequently, ferroptosis inhibitor and activator, Ferrostatin-1 and Erastin, were taken to explore the effect of ferroptosis on the regulation function of USP43 in ALI. Finally, co-immunoprecipitation (Co-IP), ubiquitination and rescue assays were conducted to determine the regulation mechanism of USP43.
The expression of USP43 was up-regulated during ALI. Usp43-KO mice exhibited aggravated lung injury, inflammation and ferroptosis. Consistently, USP43 knockdown exacerbated LPS-stimulated cellular damage, inflammation and ferroptosis, while its overexpression exerted the opposite effect in vitro. Furthermore, the regulation effects of USP43 on ALI mainly depended on ferroptosis by administering a ferroptosis inducer and inhibitor, respectively. Mechanistically, USP43 was found to inhibit K48-linked polyubiquitination of solute carrier family 7 member 11 (SLC7A11), thereby stabilising SLC7A11. Overexpression of SLC7A11 rescued the ferroptosis, cellular and lung tissue injury and inflammation aggravated by USP43 knockdown or deficiency.
USP43 prevents the progression of ALI by mediating K48-linked deubiquitination of SLC7A11, thereby inhibiting ferroptosis. Targeting USP43 may represent a potential therapeutic strategy for ALI treatment by enhancing SLC7A11 stability and inhibiting ferroptosis.
USP43 has been proven to be upregulated during LPS-induced ALI. This study is the first to demonstrate that USP43 can inhibit the progression of LPS-induced ALI by suppressing ferroptosis. This study proved that USP43 can interects with SLC7A11 and removes the K48-linked ubiquitinaiton of SLC7A11, thereby enhances the stability of it and subsequently inhibiting ferroptosis during the LPS-induced ALI process. The regulation of USP43 on LPS-induced ALI mainly depends on SLC7A11, and USP43 is expected to become a new target for the treatment of ALI/ADRS.Chronic respiratory diseaseCardiovascular diseasesPolicy -
Diagnostic accuracy of circulating long noncoding RNAs in hepatocellular carcinoma: a systematic review and meta-analysis.3 weeks agoHepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely due to late diagnosis and the limited sensitivity of current screening biomarkers such as alpha-fetoprotein (AFP). Circulating long noncoding RNAs (lncRNAs) have recently emerged as promising, noninvasive biomarkers that may reflect the molecular mechanisms underlying hepatocarcinogenesis. This systematic review and meta-analysis aimed to comprehensively evaluate the diagnostic accuracy of circulating lncRNAs for detecting HCC.
A systematic search of PubMed, Scopus, Web of Science, and Embase was performed up to March 2025 following the PRISMA-DTA guidelines. Eligible studies reporting the diagnostic performance of circulating lncRNAs for HCC were included. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a bivariate random-effects model. Subgroup analyses were conducted according to sample type, detection method, and reference standard.
Eighty-one studies encompassing over 6,000 participants were included. The pooled sensitivity and specificity of circulating lncRNAs were 0.83 (95% CI: 0.80-0.86) and 0.80 (95% CI: 0.75-0.84), respectively, with an area under the summary receiver operating characteristic (SROC) curve of 0.88. Serum-based assays showed slightly higher accuracy than plasma-based assays. lncRNAs also demonstrated good diagnostic performance in discriminating HCC from cirrhotic patients, as well as from patients with HBV-positive and HCV-positive status.
Circulating lncRNAs exhibit high diagnostic accuracy and hold significant potential as complementary biomarkers to AFP for early HCC detection. Their mechanistic roles in tumor proliferation and immune regulation underscore their value in molecular diagnosis and personalized management of liver cancer.Cardiovascular diseasesPolicy -
"Touching Beyond the Body": A Qualitative Study of Spiritual Care Experiences among Hemodialysis Nurses in Türkiye.3 weeks agoThis study aimed to examine in depth the spiritual care experiences of nurses working in hemodialysis units in Türkiye. A qualitative phenomenological design was employed, and data were collected through in-depth, face-to-face, semi-structured interviews with 10 hemodialysis nurses working in public hospitals in western Türkiye. A total of 12 eligible nurses were invited, and 10 participated in the study, resulting in a response rate of 83.3%. The data were analyzed using Colaizzi's seven-step phenomenological analysis method with MAXQDA 2022 software. The findings were grouped under four main themes: definition of spiritual care, effects of spiritual care, barriers to spiritual care, and suggestions for improving spiritual care. The results showed that nurses perceive spiritual care as a holistic approach involving empathy, respect for privacy, therapeutic communication, and emotional support. However, excessive workload, lack of time, and insufficient organizational support were identified as key barriers. Strengthening institutional support and training programs is recommended to improve the integration of spiritual care into clinical practice.Mental HealthAccessCare/Management
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Identifying facilitators and barriers to using trauma-informed care at a level 1 trauma center.3 weeks agoMillions of individuals sustain traumatic injuries each year, yet the emotional impact of hospitalization and acute medical care remains understudied. Trauma-informed care (TIC) offers a framework for reducing retraumatization and supporting both patients and providers, but little is known about how TIC is understood or applied in trauma centers. This qualitative study used a human-centered design approach to examine healthcare workers' experiences, perceptions, and training needs related to TIC within a Level 1 trauma center to inform development of a training on TIC. This study employed a qualitative approach guided by principles of Human-Centered Design (HCD) to explore healthcare workers' perceptions, experiences, and training needs related to trauma-informed care (TIC) within a high-acuity trauma setting. Healthcare workers, including nursing assistants, registered nurses, physical therapists, advanced practice providers, and physicians were included as key informants in defining the relevance, challenges, and applicability of trauma-informed practice at the trauma center. Participants were recruited from the Trauma and Acute Care Division and hospital unit serving predominantly traumatically injured patients. Using thematic reflexive analysis, semi-structured interviews (range: 10-25 min) with 20 multidisciplinary staff revealed three overarching themes: the emotional toll and burnout associated with trauma work; TIC-aligned practices (including empathetic communication and perspective taking); and training needs including format and content and skills needed to deliver TIC effectively. Participants emphasized the need for practical, hands-on training tailored to the realities of trauma care. Trauma-informed approaches have the potential to improve patient recovery, reduce psychological distress, and lessen strain on healthcare systems. Study findings can inform broader behavioral medicine practices by guiding the development of scalable TIC interventions that meet providers' identified needs which are adaptable to trauma centers, emergency care, and other high-acuity medical settings to enhance patient-centered care.Mental HealthAccess
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The incidence and risk factors for incarceration for violence after traumatic brain injury.3 weeks agoThere is increasing evidence to suggest that Traumatic Brain Injury (TBI) is implicated in increased incarceration for violence. TBI is commonly experienced by vulnerable populations who are at greater risk of violent offending due to health and social comorbidities. However, the impact of comorbid risk on outcomes of incarceration for violence is underexplored. Through retrospective data linkage, the current study aimed to identify the rate of incarceration for violence post-TBI and explore the impact of key risk factors in a cohort of 5899 survivors of TBI identified through hospital emergency department (in Victoria, Australia) presentations for TBI (age: M = 21.60, SD = 2.29; sex: males n = 4130, 70.01%, females n = 1769, 29.99%; Indigenous status: Indigenous Australian n = 136, 2.31%, non-Indigenous Australian n = 5763, 97.69%).
The incidence rate for incarceration for violence was 409.31 per 100,000 person-years with incarceration occurring, on average, 2.63 (IQR = 4.56) years post-TBI. Risk of incarceration was almost four times higher for individuals who reported pre-TBI incarceration for violence (HR = 3.80, 95% CI [1.89-7.69]) but was not impacted by pre-TBI incarceration for non-violent crimes. Post-TBI incarceration for non-violent crimes demonstrated an increased risk that ranged from 11 (one incarceration, 95% CI [6.66-19.43]) to almost 25 times higher (four or more incarcerations 95% CI [9.42-64.39]) compared to individuals who were not incarcerated. Pre-and-post-TBI substance and substance use treatment demonstrated an increased risk for incarceration for violence that was 17 (pre-TBI: HR = 17.27 95% CI [11.44-26.06]), 19 (post-TBI: HR = 19.32, 95% CI [13.32-28.02]), and almost three (substance use treatment: HR = 2.46-4.67, 95% CI [1.55-18.53]) times higher than those without indicators of substance use or substance use treatment.. Comparatively, only pre-TBI mental health (HR = 4.16, 95% CI [2.62-6.57]) and mental health treatment (HR = 2.68-5.3, 95% CI [1.11-28.03]) significantly increased risk by four and almost three times respectively.
The findings suggest TBI is a key risk factor for incarceration for violence that is exacerbated by health and social vulnerabilities experienced pre-TBI and post-TBI. There may be key opportunities prior to prison contact and after release from prison to provide appropriate intervention that accommodates for TBI-related changes and effectively addresses needs before they manifest into violent offending outcomes.Mental HealthAccess -
Prenatal exposure to nicotine and postpartum depression: a systematic review and meta-analysis.3 weeks agoPostpartum Depression (PPD) is the most common mental health complication of childbirth, and has short-term and long-term consequences for mother, child, and the entire family. PPD is a function of several factors. Prenatal exposure to nicotine (PEN) by Active Tobacco Smoking (ATS), Secondhand Smoking (SHS), or Electronic Nicotine Products (ENPs) is a major potential risk factor. This systematic review and meta-analysis aim to summarize and evaluate all evidence regarding the association between PEN and PPD.
We searched the following databases, PubMed, Medline, Cochrane, EMBASE, and CINHAL, for studies published between Jan.1st ,2000&Sep.19th ,2024, with the outcome PPD. Studies quality was assessed using the Newcastle-Ottawa Scale. Pooled Prevalence (PP) was calculated using the Freeman-Tukey Double Arcsine Transformation method. Pooled Odds Ratio (pooled-OR) was estimated using a random-effects model. Sensitivity analysis was conducted using the leave-one-out technique.
Of 29 studies in the systematic review, 26 included in the meta-analysis. PP of PPD was 0.15,(95% CI[0.12-0.17]; I2 = 99.80%,p < 0.001). Pooled-OR for ATS 1.96,(95%CI[1.59-2.41]; Z = 6.46,p < 0.001), 1.22,(95%CI[0.69-2.18], Z = 0.69,p = 0.49) for SHS, and 1.14,(95%CI[0.82-1.58,Z = 0.78,p = 0.43) for ENPs. While the overall Pooled-OR for all PEN was 1.74,(95%CI[1.44-2.12]; Z = 5.59,p < 0.001), funnel plots and Egger test showed no evidence of publication bias. Sensitivity analysis confirmed the robustness of the findings.
This meta-analysis reveals that the accumulated evidence shows a significant association between prenatal PEN and PPD; though this final finding should be interpreted cautiously due to the high heterogeneity. Therefore, the exposure-stratified estimates represent the principal findings of this meta-analysis. The findings indicates a significant association between prenatal ATS and PPD, but no clear conclusion could be drawn about prenatal SHS or ENPs use due to the limited number of studies. There is a need for future studies that prospectively assess the impact of SHS and ENP on PPD.Mental HealthAccessAdvocacy -
Occupational therapists' experiences in Australia's primary mental health funding scheme: Navigating complexity in a constrained system.3 weeks agoOccupational therapists in the Australian context provide significant value to mental health, including through Better Access, a Medicare initiative that gives individuals access to up to 10 sessions with a psychologist, social worker, or occupational therapist following a referral from a medical practitioner. However, the experiences of occupational therapists working under the initiative are not widely understood, with no recent occupational therapy-specific research. This study aims to explore the experiences of occupational therapists working under Better Access, their distinct role, and how the system shapes the care clients receive.
The study used a qualitative, inductive approach. Thirteen occupational therapists who work with people funded by Better Access participated in 30-minute, semi-structured interviews. Data were analysed via thematic analysis.
The lead researcher for this study has lived experience of mental illness and Better Access, but further consumer and community involvement was not undertaken.
Analysis generated themes highlighting the complexity of occupational therapy practice within a psychology-centric system. Participants described how occupational therapists drew on specialised skills to support clients with complex needs, yet worked within structural constraints such as restrictive practice rules, session caps, and limited remuneration. Themes also reflected the undervaluation of occupational therapy and the need for ongoing advocacy to ensure equitable access to services, appropriate funding, and recognition of the profession's contribution.
The design of Better Access restricts the ability of occupational therapists to provide meaningful and sustainable occupational therapy services. Findings provide further evidence that longstanding issues identified in early research have persisted and that the burden occupational therapists face of consistently advocating for the profession and their clients is symptomatic of broader structural inequities. Findings highlight the need for systemic reform.Mental HealthAccessCare/ManagementAdvocacy -
It's not just what you have, but when: The role and timing of developmental assets in the mental health of young adults.3 weeks agoAs the mental health of young adults is declining, finding effective strategies to support them is crucial. Young people who possess, or are exposed to, more developmental assets report higher well-being and fewer mental problems. Developmental assets are promotive factors that include both individual strengths, like strong social skills and positive identity, and external resources, like supportive relationships and safe living conditions. However, no longitudinal study has yet examined when in development the presence of developmental assets is most impactful. This study aimed to identify which life-course hypotheses-sensitive period, accumulation, or recency-best explain the associations between developmental assets across childhood and adolescence and mental health in emerging adulthood. Data were drawn from 1344 White, French-speaking participants of the Quebec Longitudinal Study of Child Development (57% female), a population-based cohort of children born in the Province of Quebec in 1997/1998 and followed up until now. Developmental assets, measured as both broad dimensions (internal and external) and specific categories (e.g., social competencies, support), were assessed across development from ages 5 (2003) to 17 years (2015) using reports from mothers, teachers, interviewers, and the youth themselves. Self-reports of life satisfaction, happiness, and symptoms of anxiety and depression were collected twice, at ages 19 (2017) and 22 years (2020). Although all effect sizes were small, findings from the Structured Life-Course Modeling Approach showed that both internal and external assets present later in adolescence were most beneficial in supporting life satisfaction, thereby supporting the recency hypothesis. In contrast, a sensitive period hypothesis best explained the associations between external assets and both anxiety and depression symptoms, with assets present during the transition to secondary school (age 12 years) showing the strongest associations. When examining specific asset categories, social competencies, positive identity, support from families, schools, and neighborhoods, and safety emerged as especially salient for later mental health. This study highlights the importance of understanding when and which assets matter most to inform more developmentally targeted approaches promoting youth well-being.Mental HealthAccessAdvocacy