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ABSTRACT Aims Religiosity and spirituality (R/S) are generally associated with a more favourable cardiovascular risk profile, but longitudinal evidence is limited. We examined whether multidimensional R/S predicts its future behavioural and biological components. Methods This prospective cohort study analysed 6,844 adults aged ≥50 (56% women; mean R/S score 2.1; 20% weekly attenders; 81% Christian) from waves 4–7 of the English Longitudinal Study of Ageing (ELSA). Behavioural outcomes included smoking, exercise, alcohol intake, and fruit and vegetable consumption; biological outcomes included blood pressure (BP), haemoglobin A1c (HbA1c), and the inflammatory risk markers C-reactive protein (CRP) and fibrinogen. R/S was assessed with four items from the Santa Clara Strength of Religious Faith Questionnaire. Hierarchical linear and logistic regressions adjusted for age, sex, wealth, education and ethnicity; biomarker models also adjusted for health behaviours and body mass index. Results Greater spirituality ( B =−0.019; 95%CI[−0.036,−0.003]), daily prayer/meditation ( B =−0.017; 95%CI[−0.032,−0.002]), participation in organized religion ( B =−0.017; 95%CI[−0.032,−0.002]), and importance of religious faith ( B =−0.017; 95%CI[−0.033,−0.002]) were independently associated with lower fibrinogen levels. Daily prayer/meditation also independently predicted higher fruit and vegetable intake ( B =0.004; 95%CI[0.000,0.008]). However, frequent attendance (OR=0.846; 95%CI[0.730,0.982]), the significance of faith (OR=0.935; 95%CI[0.879,0.994]), and religious purpose (OR=0.939; 95%CI[0.884,0.997]) independently reduced the odds of meeting exercise recommendations. Similarly, frequent attendance was associated with higher HbA1c ( B =0.002; 95%CI[0.000,0.005]). There were no independent associations with CRP or blood pressure. Conclusion R/S showed mixed prospective associations with the cardiovascular risk profile: favourable for fibrinogen and fruit and vegetable intake, unfavourable for physical activity and HbA1c. LAY SUMMARY We examined whether religious and spiritual involvement was related to later heart-related health behaviours and blood measurements in more than 6,800 English adults aged 50 and over. The associations ran in both directions, and the study cannot show that religion or spirituality causes these changes. Stronger religious and spiritual involvement was associated with lower fibrinogen, a blood protein linked to clotting. Daily prayer or meditation was associated with eating more fruit and vegetables. Regular attendance at religious services was associated with less physical activity and higher blood sugar. GRAPHICAL ABSTRACT

ABSTRACT Objective To provide expert recommendations for the development of a specialty bipolar clinic that promotes best clinical practices for the delivery of safe and effective care. Methods Members of the National Network of Depression Centers (NNDC) Bipolar Clinics Work Group met in a series of 1‐h monthly video calls over 18 months to discuss all aspects of their respective institution's bipolar clinics, including services provided, administrative processes, staffing models, characteristics of patients treated, patient volumes, finances, and research. The group also invited psychiatrists from outside of the NNDC who ran large bipolar clinics to contribute their thoughts and experiences on the subject. In addition, the NNDC sent a 20‐question survey to all 27 sites asking clinic directors specific questions about their bipolar clinics, if applicable. Further meetings and discussions incorporating results from the survey took place to produce a comprehensive set of recommendations. Results Twenty‐one of 27 NNDC sites (81%) responded to the survey. Twelve of 21 (57%) sites had a specific bipolar clinic, and another 4 (19%) were looking to start one. Clinics were based in university settings. The meetings, clinic survey, and discussions resulted in 10 recommendations describing services and operations for bipolar specialty clinics. Conclusions Given the complexity of bipolar disorder, specialty clinics are important to enhance care. Clinics with a wide array of services that include consultation, medication management, bipolar‐specific psychotherapies, and patient/family psychoeducation provide the most comprehensive care. Challenges to these clinics include maintaining ongoing patient access as well as ensuring long‐term financial stability.

Précis: Glaucoma patients of similar age and educational level, compared with healthy individuals, exhibit a greater number of saccades and fixations during eye-tracking-aloud reading, resulting in reduced reading speed. Purpose: To evaluate reading performance in patients with glaucoma compared with controls using an eye tracker and to explore the potential confounding effects of patients’ contrast sensitivity and cognition. Materials and Methods: A cross-sectional study was conducted with 111 participants (57 with glaucoma and 54 controls) with a best-corrected visual acuity of ≥0.5 logMAR. Cognition was assessed using the Montreal Cognitive Assessment, and contrast sensitivity was measured with the Freiburg Visual Acuity and Contrast Test. A reading performance evaluation was conducted using the Minnesota Low Vision Reading Test displayed on slides on a computer screen. Reading speed was calculated in words per minute, and an eye tracker was used to analyze saccade and fixation patterns during the reading task. Results: Mean age was 61.8 (±11.6) and 66.5 (±13.7) in the glaucoma and control groups, respectively ( P =0.05). Best-corrected visual acuity was 0.18 (±0.16) and 0.04 (±0.10) logMAR in the glaucoma and control groups, respectively ( P <0.001). Montreal Cognitive Assessment score was 21.8 (±3.5) in the glaucoma and 21.4 (±4.0) in the control group ( P =0.566). A total of 26% of the glaucoma group and 33% of the control group had at least a primary education. Controls read faster and showed fewer saccades and fixations than patients with glaucoma ( P <0.05) across all 5 slides. Conclusions: Patients with glaucoma exhibit poorer reading performance, as evidenced by eye-tracking data, compared with controls of similar age, cognitive function, and educational level.

Abstract Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.

Background: Mindfulness-based interventions may improve cardiovascular health (CVH) by supporting behavioral change across multiple risk factors. This study evaluated the impact of Mindfulness-Based Blood Pressure Reduction (MB-BP), a mindfulness program targeting hypertension-related behaviors ( Image 1 ), on CVH using the American Heart Association’s Life’s Essential 8 framework. Methods: This secondary analysis of parallel-group, phase 2 randomized clinical trial evaluated the effects of MB-BP on CVH in 201 participants with elevated office BP (≥120/80 mmHg). The MB-BP group (n=101) received an 8-week program focused on mindfulness training and education targeting diet, physical activity, medication adherence, alcohol use, and stress, whereas the control group (n=100) received enhanced usual care ( Image 2 ). CVH was assessed using available Life’s Essential 8 components: systolic blood pressure, body mass index (BMI), diet (DASH adherence), physical activity, smoking, and sleep duration. Generalized estimating equations evaluated intervention effects through six months. Results: At six months follow-up, MB-BP participants significantly improved composite CVH scores compared to controls (standardized mean difference: 0.144; 95% CI: 0.023, 0.266) ( Image 3 ). MB-BP influenced most CVH components in healthier directions at trend levels, with the strongest responses for physical activity (47.9 MET min/week; 95% CI: -16.5, 112.3), sleep (0.34 hours/night; 95% CI: -0.10, 0.78), systolic blood pressure (-4.95 mmHg; 95% CI: -10.34, 0.44) and DASH diet score (0.27, 95% CI: -0.15, 0.69). Conclusions: MB-BP led to modest but clinically significant improvements in CVH, driven by multiple Life’s Essential 8 components. These findings suggest that MB-BP may be an effective behavioral intervention to support CVH and reduce risk for cardiovascular disease. ClinicalTrials.gov Preregistration Identifiers: NCT03256890, NCT03859076

GGGGCC (G 4 C 2 ) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Toxicity is thought to result from the accumulation of either repeat RNAs and/or dipeptide repeat proteins (DPRs) translated from repeat-containing transcripts through repeat-associated non-AUG (RAN) translation. To disentangle RNA from DPR toxicity, we mutated a CUG codon predominantly used to initiate DPR translation from all three reading frames. This mutation disrupted DPR synthesis while preserving the expression of repeat-containing RNAs. Despite the accumulation of RNA foci, behavioral deficits and pathological abnormalities, including p-TDP-43 inclusions, STING activation, motor neuron loss, neuroinflammation, and increased plasma neurofilament concentration, were alleviated in C9ORF72 mice. Base editing of the CUG codon also improved molecular phenotypes and survival in patient induced pluripotent stem cell–derived neurons, which highlights the potential of therapeutically targeting DPR production rather than repeat RNAs.

Abstract Viral infections are estimated to contribute to 12% to 20% of all cancers worldwide, with virus-driven malignancies disproportionately affecting low- and middle-income countries, whereas metabolic and nonviral factors predominate in high-income regions. Key oncogenic viruses that cause solid tumors include high-risk human papillomaviruses, Epstein–Barr virus, hepatitis B virus, hepatitis C virus, Kaposi sarcoma–associated herpesvirus, and Merkel cell polyomavirus. Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy by boosting immune responses against tumors. Although viral infection–associated tumors often exhibit “hot” immune profiles, clinical outcomes with ICIs remain inconsistent. Some studies report improved survival in virus-associated cancers, whereas others indicate no clear benefit, which might reflect high variability in tumor microenvironments and immune responses. In this review, we aim to explore the direct and indirect contribution of different viruses to carcinogenesis in solid tumors, with a particular focus on immunotherapy effectiveness based on infection status.

Abstract Introduction Cannabidiol has been shown to exert significant anti-inflammatory effects and has demonstrated efficacy in murine models of autoimmune myocarditis, pericarditis, and heart failure. The ARCHER Study assessed whether a pharmaceutically produced cannabidiol formulation showed beneficial effects on cardiac magnetic resonance (CMR) endpoints known to predict prognosis in this patient population. Methods In a multicentre international double-blind placebo-controlled phase 2 study, we randomly assigned 109 patients within 10 days of CMR confirmed diagnosis of acute myocarditis to 12 weeks of pharmaceutically produced oral cannabidiol (active) or placebo. Dose was titrated up to 10 mg/kg of body weight twice daily. Primary endpoints were the difference in extracellular volume (ECV) and global longitudinal strain (GLS) measured by CMR at week 12. Other CMR endpoints included left-ventricular ejection fraction (LVEF), LV mass, intracellular volume (ICV), LV end-diastolic and end-systolic volumes (LVEDV, LVESV), and left-atrial end-systolic volume (LAESV). Results All randomized patients (56 active/53 placebo) completed the study with no loss to follow-up. Study drug appeared safe and well tolerated. Baseline mean ECV 38.9 ± 10.9 ml, GLS −15.3 ± 3.6%, and LVEF 60.6 ± 9.9% were consistent with mild to moderate myocarditis and predominantly intact LV function. Week 12 mean ECV was 33.6 ml in the active group and 37.3 ml in the placebo group, a difference of −3.7 ml, confidence interval (CI): −7.4 to 0.1; P = .0538; GLS was −16.0% in the active group and −15.9% in the placebo group, difference of −0.1, CI: −1.2 to 1.1; P = .90. Left ventricular mass was significantly reduced in the active group at 121.1 g compared to placebo 130.3 g, a difference of −9.2, CI: −16.4 to −2.1; P = .0117. In terms of remodelling, LAESV was significantly reduced in the active group (−8.1 ml; P = .0376) while the reduction in LVEDV failed to reach significance (−7.4 ml; P = .098). Conclusion In mild-to-moderate acute myocarditis, treatment with pharmaceutically manufactured cannabidiol was not associated with a statistically significant change in myocardial ECV or GLS, although a trend towards reduction in ECV was observed. In addition, improvement in other potential markers of myocardial recovery, including a significant reduction in LV mass, was seen in the active treatment group. Further investigation of the therapeutic potential of this therapy in inflammatory cardiac conditions is warranted.

Importance The choice of induction agent during rapid sequence intubation (RSI) of critically ill adults may affect clinical outcomes. Although ketamine and etomidate are frequently used for RSI, their comparative effectiveness remains controversial. Objective To compare the safety of etomidate vs ketamine for emergency RSI in critically ill adults. Design, Setting, and Participants This cohort study used a target trial emulation with observational data collected between March 1, 2022, and April 30, 2024, from 18 emergency departments across Brazil, with data from the Brazilian Airway Registry Cooperation. Adults who underwent RSI and received either etomidate or ketamine as a sole hypnotic agent were included; those with preintubation cardiac arrest or immediate postintubation transfer were excluded. Exposure Administration of etomidate or ketamine as the induction agent for RSI. Main Outcomes and Measures The primary outcome was 28-day in-hospital mortality. Secondary outcomes included 7-day in-hospital mortality, first-attempt intubation success, and major adverse events (new hemodynamic instability, severe hypoxemia, and cardiac arrest) within 30 minutes after intubation. Inverse probability of treatment weighting was used to adjust for confounding. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were used to compare outcomes between groups. Results Among 1810 patients (median age, 64 years [IQR, 50-74 years]; 1048 men [57.9%]), 514 received ketamine and 1296 received etomidate. The median shock index was higher in the ketamine group than the etomidate group (0.81 [IQR, 0.65-1.01] vs 0.76 [IQR, 0.59-0.99]), and preintubation vasopressor use was more common in the ketamine group than the etomidate group (191 of 514 [37.2%] vs 391 of 1296 [30.2%]). Weighted 28-day mortality was higher with etomidate than ketamine (60.5% [95% CI, 57.2%-63.8%] vs 54.4% [95% CI, 45.0%-63.9%]; RR, 1.14 [95% CI, 1.03-1.27]; RD, 7.6% [95% CI, 2.0%-13.3%]). Seven-day mortality was also higher with etomidate than ketamine (35.2% [95% CI, 32.0%-38.3%] vs 30.1% [95% CI, 23.5%-36.7%]; RR, 1.19 [95% CI, 1.04-1.35]). New hemodynamic instability within 30 minutes after intubation was more frequent with ketamine (24.2% [95% CI, 20.4%-28.0%] vs 18.9% [95% CI, 16.7%-21.0%]; RR, 0.78 [0.64-0.95]). There were no statistically significant differences in the other secondary outcomes. Conclusions and Relevance In this cohort study of critically ill adults undergoing RSI, etomidate use was associated with higher in-hospital mortality at 7 and 28 days compared with ketamine. These findings highlight the need for definitive randomized clinical trials to compare both agents.