To examine rest-activity rhythms and objective sleep dimensions with all-cause mortality, with heart-disease mortality as a supportive secondary outcome, among adults with cardiovascular-kidney-metabolic syndrome.

We analyzed National Health and Nutrition Examination Survey 2011-2014 data linked to mortality through 2019 among adults with archived cardiovascular-kidney-metabolic stages 1 to 4. Rest-activity rhythm metrics (interdaily stability, intradaily variability, relative amplitude) and sleep parameters (duration, efficiency, timing variability) were derived from wrist-worn actigraphy. Survey-weighted Cox models incorporated mobile examination center weights, strata, and primary sampling units.

Among 3061 participants, 274 all-cause and 79 heart-disease deaths occurred. Higher intradaily variability was associated with higher all-cause mortality (hazard ratio [HR] per 0.1 unit, 1.15; 95% confidence interval [CI], 1.08-1.23), whereas higher relative amplitude was associated with lower mortality (HR per 0.1 unit, 0.74; 95% CI, 0.66-0.82). Longer mean sleep duration (HR per hour, 0.82; 95% CI, 0.74-0.91) and higher sleep efficiency (HR per 0.1-unit increase, 0.70; 95% CI, 0.57-0.86) were associated with lower all-cause mortality, whereas greater sleep-midpoint variability was associated with higher all-cause mortality (HR per hour, 1.26; 95% CI, 1.04-1.52). Associations of relative amplitude and mean sleep duration with all-cause mortality were nonlinear. Heart-disease mortality findings were supportive.

Greater rest-activity rhythm fragmentation, lower rest-activity rhythm amplitude, and several sleep dimensions were associated with all-cause mortality. These findings do not establish causality or clinical thresholds.

Elite athletes represent a unique population within competitive sports. Despite repeated cardiovascular screening during their careers, they may harbour clinically silent but potentially serious cardiovascular diseases. Therefore, cardiovascular evaluation in elite athletes may require a sensitive and comprehensive diagnostic approach.

We analyzed 1505 elite athletes, undergoing comprehensive PPS including resting ECG, transthoracic echocardiography (TTE), and cardiopulmonary exercise testing (CPET). Major cardiovascular abnormalities (MCA) and cardiomyopathies were established according to the final clinical diagnosis, served as the reference standard. Sensitivity, specificity, positive and negative predictive values (NPV), and ROC analyses were assessed for ECG alone and for ECG combined with CPET or TTE.

MCA were identified in 17 athletes (1.13%), including 7 cardiomyopathies (0.46%) and 6 channelopathies (0.40%). CPET identified additional cardiomyopathies through exercise-induced arrhythmias, including cases not detected by resting ECG, whereas TTE identified structural and coronary abnormalities not evident on ECG. Resting ECG showed a sensitivity of 58.8% and specificity of 94.0% for MCA, with a NPV 99.5%. The addition of CPET increased sensitivity to 82.4%, although specificity decreased to 82.2%. ECG + TTE achieved a sensitivity of 76.5% and specificity of 91.5%. ROC analysis showed AUCs of 0.76 for ECG, 0.82 for ECG + CPET, and 0.84 for ECG + TTE for MCA.

In this highly selected cohort of elite athletes, integrating ECG, CPET, and TTE provided complementary diagnostic information and increased the detection of MCA compared with resting ECG alone. These findings support the feasibility of a comprehensive cardiovascular evaluation model in highly selected athletes evaluated within specialized sports cardiology settings.

Patients with type 2 inflammation-associated diseases are often treated with multiple formulations of corticosteroids. Long-term risks of using combinations of local corticosteroids are poorly characterised.

Using Danish nationwide databases, investigate associations between local corticosteroid exposure and 11 corticosteroid exposure-associated conditions compared to non-users, and eventual dose-response relationship for exposed individuals.

Systemic corticosteroid-naïve adults who redeemed inhaled, nasal and/or topical corticosteroids 2000-2012 were matched with non-initiators and followed for up to 23 years. Overall (inhaled, nasal and topical) exposure was calculated for 6-month periods as low (<1.25 daily prednisolone-equivalent mg), moderate (1.25-2.5 mg) or high (>2.5 mg). Competing risk Cox models with time-varying effects were used, presented as HR per additional 6-month period of exposure.

Overall, 292,393 local corticosteroid users were included (mean age 45, 47.7% female). Corticosteroid exposure-associated condition incidences were generally low, but all conditions had higher subdistribution-HRs in users, ranging from 1.4 to 3.8 for cataracts and obesity (p<0.001).For local corticosteroid users, increased risk per 6-month exposure was observed for osteoporosis (low-high dose: HRs 1.01-1.10), obesity (1.03-1.03) and pneumonia (1.03-1.15). Risk of cardiovascular disease, heart failure, cataract and gastroesophageal reflux disease increased with high-dose exposure only at HRs 1.03, 1.02, 1.04 and 1.04 per additional 6-month period of exposure, respectively.Stratified by formulation, high-dose inhaled and topical corticosteroids demonstrated the strongest associations.

In individuals using local corticosteroids, the overall corticosteroid burden, including shorter periods of high-dose exposure, associates with corticosteroid exposure-associated adverse events albeit with generally low incidence and hazard.

Heme oxygenase-1 (HO-1) participates in vascular redox regulation, but its context-dependent relationships with ferroptosis-associated endothelial injury and vascular-cell functions remain incompletely defined.

Human umbilical vein endothelial cells (HUVECs), human aortic endothelial cells (HAECs), and human aortic smooth muscle cells (HASMCs) were examined using FAC/RSL3 treatment, hydrogen peroxide, iron chelator Dp44MT, HO-1 inducer cobalt protoporphyrin (CoPP), HO-1 inhibitor Zn(II) protoporphyrin IX (ZnPP), HO-1 knockdown, and HO-1 overexpression. Outcomes included viability, lipid peroxidation, Annexin V/PI staining, total assay-detectable cellular iron, mitochondrial Fe²⁺-associated fluorescence, ROS, protein abundance, proliferation, tube-network formation, and collagen-gel contraction.

FAC/RSL3 treatment produced cell injury accompanied by increased lipid peroxidation and sensitivity to liproxstatin-1. Dp44mT reduced FAC-associated total cellular iron and mitochondrial Fe²⁺ signals and attenuated several injury-associated readouts. Pharmacological and genetic modulation of HO-1 was associated with changes in FAC/RSL3/Dp44mT responses, ROS levels, proliferation, and tube network formation. In HASMCs, CoPP treatment was associated with reduced ROS levels and collagen-gel contraction, as well as altered protein abundance of GDF15 and WISP1.

The findings identify context-dependent associations between HO-1 modulation and vascular-cell responses in vitro. This study highlights HO-1 as a versatile regulator of vascular cell function, providing a critical molecular framework for developing novel therapeutic strategies to treat atherosclerosis and related cardiovascular diseases.

Long COVID is a multi-system, heterogeneous condition that manifests as new or worsened symptoms lasting at least 3 months following acute SARS-CoV-2 infection, often despite normal results on routine diagnostic testing. Common manifestations include fatigue, post-exertional malaise, cognitive impairment, and orthostatic intolerance. Primary care clinicians are uniquely positioned to identify and manage Long COVID due to their longitudinal relationships with patients and holistic understanding of their patients' health. However, diagnostic uncertainty, time constraints, and limited access to specialty care present significant challenges, and sometimes hesitation, to addressing Long COVID in the primary care setting. This focused narrative review provides a pragmatic, primary care-focused approach for the evaluation and management of Long COVID. Using patient-centered vignettes, we first describe common clinical presentations. Next, we provide a framework for the pathophysiological mechanisms suspected to contribute to persistent symptoms after SARS-CoV-2 infection. We then present a simple approach to Long COVID diagnosis and management that leverages primary care clinicians' skillset and highlights unique aspects of Long COVID care (e.g., diagnostic workup to evaluate for competing or coexisting diagnoses; management strategies focused on validation and supportive care, including activity pacing, multidisciplinary rehabilitation, and consideration of symptom-based medication trials). We offer practical strategies to effectively, yet efficiently, address a possible Long COVID diagnosis within the context of brief primary care visits (e.g., prioritize the most bothersome or addressable symptom(s) first, focus on one or two symptoms each visit, leverage longitudinal follow-up). We conclude with evidence-based strategies for prevention counseling, including infection prevention and early outpatient treatment during acute infection. While we remain optimistic that reliable diagnostic biomarkers and curative treatments will one day be available, until then, this primer supports primary care clinicians in recognizing Long COVID and supporting their patients who are living with it, despite the constraints of our current healthcare environment.

Understanding how multiple housing-related inequalities coexist is crucial for addressing cumulative disadvantage in contemporary societies. Yet, the complexity of their interrelations remains insufficiently explored. This systematic review maps existing evidence on how different forms of housing and environment-related inequalities co-occur and, where examined, how these overlapping inequalities relate to physical and mental health outcomes. Guided by PRISMA protocols and supported by bibliometric and network analyses using VOSviewer and Bibliometrix, the study reviewed literature published since 2007, identifying 974 relevant papers for clustering and 53 for in-depth qualitative synthesis. The review examines the extent to which housing inequalities intersect with at least one of three wider dimensions-access to green and blue spaces, transport and infrastructure, and digital access-and how these intersections relate to health. Although nearly half of the included studies considered more than one wider dimension, research explicitly examining their combined effects remained limited, constraining understanding of cumulative disadvantage and its health consequences. Findings also reveal that vulnerable populations-including low-income households, older adults, migrants, ethnic minorities-are disproportionately affected by poor housing conditions compounded by limited access to spatial services and resources. This review calls for more integrated, longitudinal, and intersectional research to capture the complex interplay of housing conditions, wider environmental aspects, and health. It also highlights the need for inclusive urban planning and policy responses that place housing at the center of health equity strategies. Ensuring safe, affordable, and well-connected housing is both a public health priority and a foundation for sustainable urban development.

White matter (WM) microstructure is implicated in the neurobiology of substance use disorders (SUDs), yet direct comparisons across substance-dependence syndromes remain scarce. It is also unclear whether WM abnormalities relate to impulsive decision-making and substance use severity. We performed a cross-sectional, dual-centre diffusion MRI study and quantified WM microstructure using diffusion tensor imaging and neurite orientation dispersion and density imaging in 87 individuals with SUDs (48 with cannabis dependence (CUD), 16 with opioid dependence (OUD), and 23 with nicotine dependence (NUD)) and 53 nonsmoking healthy controls. Whole-brain tract-based spatial statistics and tract-specific analyses of the middle longitudinal fasciculus (MLF), a temporo-parietal tract implicated in cognitive control and valuation, were performed. OUD and CUD exhibited convergent, widespread WM abnormalities characterised by reduced fractional anisotropy and increased mean diffusivity and orientation dispersion across fronto-temporo-parietal and limbic pathways, including the superior longitudinal fasciculus, arcuate fasciculus, cingulum, and MLF. In contrast, NUD showed more circumscribed alterations observed primarily in MD and  localised mainly to anterior and callosal white matter regions. In CUD, higher MLF orientation dispersion was associated with steeper delay discounting (r = 0.41, p = 0.011). Moderated mediation analyses indicated that this association was indirectly driven by cannabis consumption, with asignificant conditional indirect effects observed only among daily users. No significant MLF-discounting associations were observed in OUD. Our findings reveal both shared and distinct WM alterations across SUDs and identify a link between MLF microstructure and impulsive choice in cannabis dependence.

Children of parents with mental health illness (COPMI) have the right to receive preventive interventions to avoid developing their own mental health and socioeconomic problems. However, access to interventions varies widely within health care and social services depending on their geographical location in Sweden. In this regard, mobile health (mHealth) interventions for COPMI provide a pathway for more equitable and sustainable preventive support.

This project aims to (1) map and assess the quality of available mHealth apps relevant to COPMI; (2) investigate experts' perceptions of COPMI needs for digital health solutions (particularly mHealth) by consulting and collaborating with an interdisciplinary reference group (scholars, child rights organizations, and IT professionals); and (3) explore the prerequisites for development, implementation, and sustainable access to future digital solutions for COPMI.

We collaborated with a reference group through a series of meetings and workshops, identifying and assessing the quality of 9 free, highly ranked apps (ie, using the well-known Mobile App Rating Scale [MARS]). All the workshop sessions were recorded and transcribed for further qualitative analysis, allowing us to document and derive our main findings.

Three out of 9 apps received high scores across the MARS dimensions of aesthetics, perceived functionality, information, and engagement in the expert heuristic evaluation using recorded demonstrations of the apps, indicating a significant lack of high-quality apps relevant to COPMI. Further findings were derived, such as the experts' preference for more general apps that are not specifically targeted to COPMI, as these could promote self-identification and reduce stigmatization. Regarding the third aim, the results showed that it was important to find an app that protected users' privacy by allowing anonymous access to digital support and that mobile apps should be complemented (or replaced) by web-based applications to improve accessibility for children who may not be allowed to download apps without parental permission.

The sustainability of digital solutions (web applications or mobile apps) for COPMI is the biggest challenge for future developments. Long-term impact requires stable funding, continuous maintenance, and partnering with established organizations that already possess the infrastructure, expertise, and reach necessary to provide ongoing support. To address the limitations in the study design and deployment issues, it is important to actively involve children through participatory and co-creational approaches when designing and developing mHealth solutions. Also, future evaluations should include privacy and data security assessments such as app permissions, privacy-policy presence, and third-party sharing.

Generative artificial intelligence (GAI) chatbots are frequently used for mental health-related questions, including suicide-related queries. User interfaces (UIs) may include additional safety controls not present in direct application programming interface (API) access (eg, moderation rules that flag or block harmful content, crisis refusal templates, or system-level instructions).

This observational cross-sectional study aimed to examine how frequently AI chatbots provide direct responses to suicide-related prompts across access modes and whether response patterns differ between consumer-facing UI and API access across models and prompt risk levels.

We evaluated how five widely used consumer AI models (ChatGPT, Claude, Gemini, Grok, and Llama) responded to 30 previously vetted suicide-related prompts spanning five clinician-assigned risk levels. Each prompt was submitted 100 times through both public-facing UI and direct API access, yielding 30,000 total responses. The primary outcome was whether a response directly answered the prompt (ie, provided specific information or guidance related to the question asked). AI responses were categorized using a blinded large language model-based classifier (GPT-4o mini), validated against independent human coding (289/300, 96.3% agreement; Cohen κ=0.89). We estimated mixed-effects logistic regression models that predicted a direct response. The primary predictors were the AI model, access mode (UI vs API), and prompt risk category.

Of the 30,000 responses, 69.8% (n=20,934) were direct. Direct responses were more common through APIs than UIs (n=11,609, 77.4%, vs n=9325, 62.2%); however, Gemini had slightly higher direct response rates via UIs than APIs (n=2301, 76.7%, vs n=2131, 71.0%). Differences in the likelihood of a direct response were most pronounced for higher-risk prompts: For very-high-risk prompts, 24.8% (n=743) of API responses were direct compared with 4.6% (n=138) of UI responses, whereas for high-risk prompts, 80.1% (n=2002) of API responses were direct compared with 48.4% (n=1209) of UI responses. Claude and Gemini had the highest direct response rates (n=4688, 78.1%, and n=4432, 73.9%, respectively) across UI and API access modes, whereas ChatGPT, Grok, and Llama had lower rates (n=3878, 64.6%; n=3870, 64.5%; and n=4066, 67.8%, respectively). In mixed-effects models, UI access was associated with lower odds of a direct response than API access (odds ratio 0.09, 95% CI 0.08-0.10). Higher prompt risk was associated with lower direct response probability, and access mode differences varied by risk level and model.

AI safety depends on how users access the model. Safety observed in a UI should not be assumed to generalize to API access or apps built on APIs. Evaluations and policies should consider access modes to ensure safety protections for individuals interacting with AI chatbots.

ObjectivesIn the United Kingdom, the majority of depression cases are identified within primary care. Receiving a diagnosis of depression may provide a way of understanding one's symptoms, legitimise experiences and initiate access to treatment pathways such as medication and psychological therapies. There is a lack of research examining the experiences of Black ethnic minorities, or those with a religious affiliation, who seek help for depression symptoms from primary care. Therefore, the objective of this study was to explore the experiences of receiving a diagnosis of depression in primary care among Black African individuals who also identify as Christian.MethodsSeven participants who self-identified as Black African and Christian took part in semi-structured interviews. Interpretative Phenomenological Approach (IPA) was used to analyse their experience of receiving a diagnosis of depression from their General Practitioner (GP).ResultsCross-case analysis identified three group experiential themes: (1) Struggling to recognise depression within identity constraints, (2) Overcoming barriers to support, (3) When you have a village: diagnosis provides opportunities.ConclusionsThe study highlighted the multifaceted meaning-making processes participants engaged in that were influenced by both strongly held religious and cultural beliefs about depression. These beliefs evolved dependent on the impact of the diagnosis, connection with God, and family influences. Further research is suggested to consider the impact of GP behaviours on the diagnostic process with individuals who are of Black African heritage and Christian.