Randomized evidence comparing conduction system pacing (CSP) and biventricular pacing (BVP) following atrioventricular node ablation in patients with refractory atrial fibrillation (AF) and heart failure (HF) remains limited. This study evaluated whether CSP with left bundle branch area pacing is non-inferior to BVP in patients undergoing atrioventricular node ablation.

CONDUCT-AF was an investigator-initiated, multicentre, randomized trial conducted across 10 European centres. Patients with refractory AF, HF with left ventricular ejection fraction (LVEF) < 50%, narrow QRS duration (≤120 ms), and N-terminal pro-B-type natriuretic peptide > 600 ng/L were randomized 1:1 to CSP or BVP. The primary endpoint was the change in LVEF after 6 months, assessed by an independent core laboratory. Secondary endpoints included echocardiographic, clinical, and procedural outcomes. Analyses followed the intention-to-treat principle.

Eighty-two patients were randomized (mean age 72 ± 7 years, 46% male). At 6 months, LVEF improved similarly in CSP {from 36% [95% confidence interval (CI) 33-39] to 46% [95% CI 44-49]; P < .001} and BVP group [from 34% (95% CI 31-36) to 46% (95% CI 43-49); P < .001]. The between-group difference was .4% (95% CI -3.1-3.8; P = .002 for non-inferiority). Changes in left ventricular volumes, clinical parameters, and composite endpoint of worsening HF or cardiovascular death were comparable between groups. Paced QRS [mean difference -14 ms (95% CI -19 to -9; P < .001)] and procedural and fluoroscopy times were significantly shorter with CSP compared with BVP.

In HF patients with refractory AF undergoing atrioventricular node ablation, CSP with left bundle branch area pacing was non-inferior to BVP for LVEF improvement at 6 months, providing comparable clinical outcomes and a favourable procedural profile.

Neonatal hypoxic-ischemic brain damage (HIBD) is the leading cause of neonatal death and long-term neurological dysfunction. Dexmedetomidine (DEX) has been shown to have neuroprotective effects, but its mechanisms in HIBD remain incompletely understood. This study aimed to explore whether DEX inhibits neuroinflammation and pyroptosis via activating adenosine monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) axis, thereby reducing HIBD. A HIBD model was established. Histological staining observed the pathological changes and neuronal survival. Primary cortical neurons were cultured to establish an oxygen-glucose deprivation/reoxygenation (OGD/R) model. DEX was used for intervene, and siAMPK was transfected to knock down AMPK expression. Inflammatory and oxidative stress indicators within brain tissue and neuronal cells were measured using enzyme-linked immunosorbent assay (ELISA) and biochemical kits. The AMPK/SIRT1 pathway and pyroptosis protein expressions were evaluated using fluorescence staining and Western blot. DEX dose-dependently reduced cerebral infarction volume, improved cerebral cortex pathological damage, enhanced neuronal nuclei (NeuN) positive neurons, decreased interleukin (IL)-6 and malondialdehyde (MDA) contents, enhanced superoxide dismutase (SOD) activity, and inhibited terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)/cleaved Caspase-1 double positive cells and N-terminal domain of Gasdermin D (GSDMD-N) protein expressions. DEX significantly upregulated p-AMPK and SIRT1 expression, whereas the AMPK inhibitor Compound C reversed the neuroprotective effect of DEX. In vitro experiments confirmed that DEX increased neuronal cell viability, reduced lactate dehydrogenase (LDH) release and propidium iodide (PI)-positive cell rate, reduced oxidative stress, and inhibited inflammatory factor release and pyroptosis-related protein expression. AMPK knockdown significantly reversed this axis activation by DEX and attenuated the neuroprotective effect of DEX. In conclusion, DEX improved neurological function in HIBD rats via the activating AMPK/SIRT1 pathway, reducing neuroinflammation and inhibiting neuronal pyroptosis.

Heart failure with reduced ejection fraction (HFrEF) links to adverse kidney and cardiovascular events. However, current machine learning (ML)-based algorithms do not include comprehensive echocardiographic features or predict adverse kidney outcomes.

We built ML models to predict 3-year all-cause mortality, major adverse cardiovascular events (MACE), and major adverse kidney events (MAKE) in retrospective HFrEF cohorts. Models were developed from 1,486 patients at Taipei Veterans General Hospital during 2011-2018 and externally validated in 246 patients from the heart-failure-post-acute-care program at Taichung Veterans General Hospital during 2020-2023. Model performance was compared to the traditional Meta-Analysis Global Group in Chronic Heart Failure score (MAGGIC), Logistic Regression (LR), and Kidney-Failure-Risk-Equation (KFRE).

For mortality, Ensemble had the highest area under receiver-operating-characteristic curve (AUROC, 0.863; 95% confidence interval [CI], 0.814-0.913; p < 0.001), outperforming MAGGIC (AUROC, 0.741; 95% CI, 0.673-0.810) with net reclassification index (NRI) of 0.294 (95% CI, 0.147-0.440; p = 0.001). For MACE, Ensemble (AUROC, 0.816; 95% CI, 0.769-0.864; p < 0.001) surpassed LR (AUROC, 0.734; 95% CI, 0.677-0.791). For MAKE, Ensemble (AUROC, 0.858; 95% CI, 0.806-0.910; p < 0.001) exceeded KFRE (AUROC, 0.647; 95% CI, 0.560-0.735) with NRI of 0.267 (95% CI, 0.133-0.396; p < 0.001). External validation confirmed good Ensemble discrimination (AUROCs of 0.803, 0.808, and 0.859 for mortality, MACE, and MAKE, respectively). An online tool (https://vghhfrefai.com/) was created for application.

Ensemble ML models with detailed clinical and echocardiographic features surpassed conventional risk scores, enabling early detection of major adverse cardiorenal events among HFrEF.

Myxoedema coma is a rare but life-threatening manifestation of hypothyroidism with high associated mortality. We present the case of a man in his sixties with known hypothyroidism and alcohol dependence who collapsed at home with profound hypothermia, refractory hypoglycaemia, hypoxia and reduced consciousness. Initial findings were easily attributable to excess alcohol; however, clinical features including periorbital oedema and bedside echocardiogram revealed moderate pericardial effusion, which prompted further investigation. Thyroid function tests confirmed severe hypothyroidism with elevated thyroid-stimulating hormone and suppressed free T3 and free T4 levels. Imaging revealed a substantial pericardial effusion and left basal pneumonia. The patient was treated with intravenous glucose, active warming, hydrocortisone and intravenous thyroxine along with antibiotics and supportive care. The patient achieved steady clinical and biochemical improvements following critical care admission. This case highlights the diagnostic challenge of recognising myxoedema coma and emphasises the importance of maintaining a high index of suspicion for endocrine emergencies.

Birth before 32 weeks' gestation, once associated with early mortality, now is commonly associated with long-term survival. Following discharge from the neonatal intensive care setting, the medical home transitions to the primary care setting. As such, primary care clinicians should be empowered with up-to-date knowledge of the spectrum of outcomes experienced by children born prematurely. This review highlights growth, pulmonary, developmental, and neurosensory outcomes in infancy and toddlerhood. For later childhood, neurological outcomes broaden to include behavioral, psychiatric, academic, and executive function outcomes. For adolescence and young adulthood, respiratory, cardiovascular, and mental health outcomes are highlighted to inform transition of care planning. The primary care clinician is encouraged to take a strengths-based approach that incorporates both surveillance for disease and promotion of healthy behaviors to optimize lifelong outcomes of individuals born preterm.

The COVID-19 pandemic has increased the demand for telepsychiatry in neurodevelopmental assessment; however, few studies have examined the interrater reliability of clinician-rated autism scales, such as the Childhood Autism Rating Scale, Second Edition (CARS2), when used remotely. Although the feasibility and validity of telehealth assessments have been explored previously, the consistency between remote and in person CARS2 ratings by different clinicians remains underinvestigated.

The objective of this study was to evaluate agreement between CARS2 total scores obtained by different evaluators using telepsychiatry and face-to-face assessments in children with autism spectrum disorder (ASD) and/or attention-deficit/hyperactivity disorder (ADHD).

In this randomized feasibility study, 75 children aged 6 to 17 years with DSM-5 (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition]) diagnoses of ASD, ADHD, or both were enrolled at 5 medical institutions in Japan; 73 of 75 were included in the final analysis. Each participant underwent 2 independent CARS2 evaluations, one face-to-face and the other via telepsychiatry, conducted by different evaluators who were blinded to each other's ratings. Remote assessments were conducted using a secure video platform with caregiver facilitation. Agreement was assessed using intraclass correlation coefficients (ICCs) for the overall sample and subgroups defined by primary diagnosis, sex, and age.

The overall ICC for CARS2 total scores between face-to-face and telepsychiatry assessments was 0.582 (95% CI 0.407-0.717), indicating moderate agreement. The ICC was 0.546 among participants with ASD as the primary diagnosis and 0.495 among those with ADHD as the primary diagnosis. Point estimates were higher among girls than boys (0.666 vs 0.495) and among children aged 11 years or older than among those aged 10 years or younger (0.676 vs 0.419). In a sensitivity analysis including all participants with an ASD diagnosis, the ICC was 0.580.

CARS2 total scores obtained through telepsychiatry showed moderate agreement with scores obtained through face-to-face assessment when the assessments were conducted by different evaluators in different settings. Higher point estimates were observed among older children and girls, although these subgroup findings should be interpreted cautiously. Telepsychiatry-based CARS2 assessment may be considered a complementary approach rather than a replacement for comprehensive face-to-face evaluation. Larger studies using more standardized assessment protocols are needed.

Depression in adolescents is a growing public health concern, with 3.5 million youth in the United States experiencing a depressive episode each year. When symptoms emerge in early adolescence, they can have lasting psychological, physical, and cognitive consequences, highlighting the urgent need for proactive intervention. Insufficient sleep-characterized by short duration, irregular timing, and poor quality-is bidirectionally linked to depression and associated with impaired cognitive performance.

This protocol provides the map for a study tracking sleep patterns and neurophysiology, as well as a range of depressive symptoms, and their dynamic interaction in shaping longitudinal cognitive trajectories.

Fifty-six youth aged 9 to 13 (mean 11.01, SD 1.39) years were enrolled in a longitudinal measurement burst design comprising 4 assessment waves at baseline, 4, 8, and 12 months. We recruited a sample of youth with a range of depressive symptom severity. Each wave included 7 consecutive days of monitoring during which participants used a personalized mobile health (mHealth) platform, HowRU app, developed by the study team, to report daily sleep patterns, thrice-daily ecological momentary assessments (EMAs), and completed a series of cognitive tasks. Youth and parents also completed validated psychosocial questionnaires to assess mood, behavioral concerns, mental health, and sleep. Sleep and physical activity were monitored remotely using a Garmin VivoSmart 5 watch and Interaxon Muse S headbands. Sleep-dependent cognitive performance was assessed with 2 declarative memory tasks (Word-Pair Associates task [WPA] and Minecraft Memory and Navigation [MMN] task), a procedural memory task (Motor Sequence task), and 2 executive functioning tasks (Operation Span [OSpan] task and Rule Switch task [RST]). For the memory tasks, participants completed training and immediate testing in the evening, followed by a retention test the following morning. The OSpan task and Rule Switch were administered twice daily (morning and evening). For all tasks, stimuli were randomized and counterbalanced across participants and testing sessions.

Funding was obtained from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant K08 HD107161), with a budget period of August 1, 2022, to July 31, 2027. Participant enrollment occurred May 2023 through October 2024. Data collection began in July 2023 and was completed in October 2025. Study participant retention and adherence rates for sleep diaries, cognitive tasks, and questionnaires were high. Primary outcomes of the study are anticipated to be published in fall 2026.

This protocol provides a robust and reproducible framework to longitudinally track youth with a range of depressive symptoms in the real world using mHealth platforms and wearable technology. Potential findings can support the identification of key developmental periods of vulnerability and resilience in youth, inform future sleep-based interventions to promote mental health, and optimize cognitive outcomes across early adolescence.

We examined the strength of intergenerational associations between midlife adults in Add Health and their Baby Boomer parents from the Add Health Parent Study (AHPS) across numerous substantive domains.

Using linked data from AHPS Phase 1 (2015-2017), a subset of parents of Add Health respondents, with new Add Health Wave VI data, we estimated intergenerational correlations between each cohort's socioeconomic status (e.g., income, economic insecurity, and educational attainment); family context (e.g., union formation, time/money transfers, and psychological traits); health (e.g., mental, physical, and behavioral); and life experiences (e.g., social integration). We harmonized measures across the two generations and estimated either Pearson (r) or polychoric (ρ) correlations depending on the level of measurement. Intergenerational correlations were further contrasted by sex, the biological relationship of the parent-child dyad, and educational attainment.

The largest correlations were found within socioeconomic and health domains, with significant correlations found for food insecurity (ρ = 0.52), educational attainment (r = 0.42), diabetes (ρ = 0.41), and obesity (ρ = 0.37). We found more significant and larger correlations for biological parent-child dyads and parent-daughter dyads. Few educational grades in intergenerational correlations were significant (e.g., health behavior and social integration).

Intergenerational correlations are stronger when there is a known shared genetic component in outcomes such as health and health behavior, but shared environments also play an important role for socioeconomic outcomes. Intergenerational similarities in advantage for the higher educated and disadvantage for the less educated are evident. Small sample sizes precluded analysis by race/ethnicity; however, AHPS Phase 2 data (2026-2027) will fill that research gap.

Recent trends of increasing midlife morbidity and mortality and widening educational disparities in the United States are concerning. This study documented the age pattern and educational disparities in health in the National Longitudinal Study of Adolescent to Adult Health (Add Health) cohort as they enter midlife, and situates the cohort relative to preceding, similar, and following cohorts in the National Health and Nutrition Examination Survey (NHANES).

Using data from Add Health and NHANES on 6 birth cohorts observed from adolescence to middle age, we characterized age patterns in general health, mental health, health behaviors, and chronic conditions within and across cohorts. We documented disparities by educational attainment, focusing on those with and without a 4-year college degree, and how such disparities emerge and evolve across the life course.

Analysis showed that general health, mental health, and chronic disease deteriorated for the Add Health cohort as they aged into midlife, while health behaviors improved. Compared to the NHANES cohorts, the Add Health cohort had worse health than older cohorts, generally worse health compared to the same birth cohort, with some exceptions, and mixed health compared to younger cohorts. Educational gradients were relatively stable across age, with some evidence of increases, while educational gradients generally increased across cohorts.

The worsening health of the Add Health cohort with age and relative to previous cohorts has important implications for aging, as this currently midlife cohort of U.S. adults will enter old age in worse health than their predecessors.

Depression in older people is a major contributor to global disease burden and functional impairment. While trait gratitude, a stable tendency to appreciate others' help, has been shown to alleviate depressive symptoms across populations, less is known about its neuroanatomical substrates and protective neuropsychological mechanisms against depression symptoms in aging populations. Here, we investigated the structural neural correlates of trait gratitude in 120 community-dwelling older women using voxel-based morphometry analysis of T1-weighted magnetic resonance imaging data. First, the whole-brain correlation analysis identified a negative association between trait gratitude and regional gray matter volume (GMV) in the right precuneus. Mediation analyses further suggested that trait gratitude could mediate the impact of regional GMV in right precuneus on depression symptoms. Critically, supplemental analyses showed that the results persisted even after controlling for anxiety and stress symptoms, as well as general personality traits. Our study presents novel evidence for the neuroanatomical basis of trait gratitude in general older women and highlights a brain-personality-symptom pathway for protecting against depression in which GMV affects depressive symptoms via trait gratitude. These findings deepen understanding of gratitude's protective role in late-life mental health while highlighting potential neurostructural markers for resilience against depression.