Circadian influences on sudden cardiac death and cardiac electrophysiology.

Cardiologists have analyzed daily patterns in the incidence of sudden cardiac death to identify environmental, behavioral, and physiological factors that trigger fatal arrhythmias. Recent studies have indicated an overall increase in sudden cardiac arrest during daytime hours when the frequency of arrhythmogenic triggers is highest. The risk of fatal arrhythmias arises from the interaction between these triggers-such as elevated sympathetic signaling, catecholamine levels, heart rate, afterload, and platelet aggregation-and the heart's susceptibility (myocardial substrate) to them.

Disparities in Patient Demographics at a Student-Run Free Clinic: Comparing Clinic Utilization to City, State, and National Trends.

Background: With 8.4% of Americans uninsured, free clinics serve as essential safety nets for underserved populations. This study compared the demographics of the patients of a student-run free to Toledo, Ohio, and national census data to evaluate health needs, barriers to care, and the characteristics of the underserved population.

An Integrated Rapid Response Model for Pediatric Patients Requiring In-Patient Medical Stabilization: Lessons Learned to Enable Regional Capacity Building.

There was an unprecedented surge in admissions for medical stabilization of pediatric patients with eating disorders during the COVID-19 pandemic in Ontario. Eleven hospitals established an integrated rapid response model to ensure timely in-patient access for these patients. This population was cared for in re-allocated community hospital beds as a result of engaging hospital leadership, strengthening partnerships, consulting experts, leveraging existing resources and developing regional bed access strategies.

The core circadian clock factor, Bmal1, transduces sex-specific differences in both rhythmic and non-rhythmic gene expression in the mouse heart.

It has been well established that cardiovascular diseases exhibit significant differences between sexes in both preclinical models and humans. In addition, there is growing recognition that disrupted circadian rhythms can contribute to the onset and progression of cardiovascular diseases. However, little is known about sex differences between the cardiac circadian clock and circadian transcriptomes in mice.

Physician Attitudes Towards Pharmacist-Prescribed HIV Post-Exposure Prophylaxis (PEP): A Survey of a State Medical Association.

Timely initiation of antiretroviral therapy (ART) for non-occupational post-exposure prophylaxis (nPEP) is crucial in preventing HIV infection and advancing efforts to end the HIV epidemic (EHE). nPEP must be administered within 72 h of high-risk exposure, ideally within 24 h. Pharmacies may play a role in increasing access to nPEP and facilitating referrals for additional care, such as PrEP.

Clockwork conditioning: Aligning the skeletal muscle clock with time-of-day exercise for cardiometabolic health.

Circadian rhythms have evolved to synchronize gene expression, physiology, and behavior with time-of-day changes in the external environment. In every mammalian cell exists a core clock mechanism that consists of a transcriptional-translational feedback loop that drives rhythmic gene expression. Circadian disruption, as observed in shift workers and genetic mouse models, contributes to the onset and progression of cardiometabolic disorders.

CosinorTest: An R Shiny App for Cosinor-model-based circadian and differential analysis in transcriptomic applications.

Summary: 'CosinorTest' application is an interactive R Shiny tool designed to facilitate circadian and differential circadian analysis with transcriptomic data using Cosinor-model-based methods. This novel application integrates multiple major statistical algorithms to identify circadian rhythmicity in gene expression data and enables the comparison of differential circadian patterns between two experimental conditions. Key features of the 'CosinorTest' app include circadian rhythmicity detection, differential patterns assessment, circadian and differential analyses with repeated measurement, and interactive data visualization, all contributing to a comprehensive understanding of underlying biological mechanisms.

A Bayesian Framework for Genome-wide Circadian Rhythmicity Biomarker Detection.

Circadian rhythms are endogenous ∼24-hour cycles that significantly influence physiological and behavioral processes. These rhythms are governed by a transcriptional-translational feedback loop of core circadian genes and are essential for maintaining overall health. The study of circadian rhythms has expanded into various omics datasets, necessitating accurate analytical methodology for circadian biomarker detection.

Disrupted rest-activity circadian rhythms are associated with all-cause mortality in patients with chronic kidney diseases.

Circadian rhythms are important biological contributors to health. Rest activity rhythms (RAR) are emerging as biomarkers of circadian behavior that are associated with chronic disease when abnormal. RAR have not yet been characterized in chronic kidney diseases (CKD).

Oops, we missed a spot: Comparing data substitution methods for non-random missing survey data in a longitudinal study.

Imputation methods for missing data may not always be applicable, namely, when the data were completely missing for the whole sample. To estimate the missing data, we compared three missing item substitution methods: (1) mean substitution; (2) last observation carried forward (LOCF); and (3) regression-predicted values. A total of 384 parents reported their 8- to 18-year-old children's anxiety level using the 9-item Screen for Child Anxiety Related Disorders at baseline (Time 1) and two later time points, drawing from a larger longitudinal study (Ontario COVID-19 and Kids' Mental Health Study).

AAV8-P301L tau expression confers age-related disruptions in sleep quantity and timing.

Sleep timing and quantity disturbances persist in tauopathy patients. This has been studied in transgenic models of primary tau neuropathology using traditional electroencephalograms (EEGs) and more recently, the PiezoSleep Mouse Behavioral Tracking System. Here, we generated a primary tauopathy model using an intracerebroventricular injection of human mutant hSyn-P301L-tau, using adeno-associated virus of serotype 8 (AAV8).

Targeted Bmal1 restoration in muscle prolongs lifespan with systemic health effects in aging model.

Disruption of the circadian clock in skeletal muscle worsens local and systemic health, leading to decreased muscle strength, metabolic dysfunction, and aging-like phenotypes. Whole-body knockout mice that lack Bmal1, a key component of the molecular clock, display premature aging. Here, by using adeno-associated viruses, we rescued Bmal1 expression specifically in the skeletal muscle fibers of Bmal1-KO mice and found that this engaged the circadian clock and clock output gene expression, contributing to extended lifespan.

A quality improvement evaluation of a standardized intervention for children with medical complexity transitioning to adult care.

Children with medical complexity have medical fragility, chronic disease, technology dependence, and high healthcare use. Their transition to adult health care at age 18 involves medical and social elements and follows no standardized process. Our goal was to improve transition readiness in children with medical complexity using a transition intervention within a Complex Care program.

The clockwork of champions: Influence of circadian biology on exercise performance.

Exercise physiology and circadian biology are distinct and long-standing fields. Recently they have seen increased integration, largely due to the discovery of the molecular components of the circadian clock and recognition of human exercise performance differences over time-of-day. Circadian clocks, ubiquitous in cells, regulate a daily tissue specific program of gene expression that contribute to temporal patterns of physiological functions over a 24-h cycle.

Alterations of the skeletal muscle nuclear proteome after acute exercise reveals a post-transcriptional influence.

Unlabelled: Exercise is firmly established as a key contributor to overall well-being and is frequently employed as a therapeutic approach to mitigate various health conditions. One pivotal aspect of the impact of exercise lies in the systemic transcriptional response, which underpins its beneficial adaptations. While extensive research has been devoted to understanding the transcriptional response to exercise, our knowledge of the protein constituents of nuclear processes that accompany gene expression in skeletal muscle remains largely elusive.

Skeletal muscle BMAL1 is necessary for transcriptional adaptation of local and peripheral tissues in response to endurance exercise training.

Objective: In this investigation, we addressed the contribution of the core circadian clock factor, BMAL1, in skeletal muscle to both acute transcriptional responses to exercise and transcriptional remodeling in response to exercise training. Additionally, we adopted a systems biology approach to investigate how loss of skeletal muscle BMAL1 altered peripheral tissue homeostasis as well as exercise training adaptations in iWAT, liver, heart, and lung of male mice.

Methods: Combining inducible skeletal muscle specific BMAL1 knockout mice, physiological testing and standardized exercise protocols, we performed a multi-omic analysis (transcriptomics, chromatin accessibility and metabolomics) to explore loss of muscle BMAL1 on muscle and peripheral tissue responses to exercise.

Auditory cortical regions show resting-state functional connectivity with the default mode-like network in echolocating bats.

Echolocating bats are among the most social and vocal of all mammals. These animals are ideal subjects for functional MRI (fMRI) studies of auditory social communication given their relatively hypertrophic limbic and auditory neural structures and their reduced ability to hear MRI gradient noise. Yet, no resting-state networks relevant to social cognition (e.

Expression of mitochondrial oxidative stress response genes in muscle is associated with mitochondrial respiration, physical performance, and muscle mass in the Study of Muscle, Mobility, and Aging.

Gene expression in skeletal muscle of older individuals may reflect compensatory adaptations in response to oxidative damage that preserve tissue integrity and maintain function. Identifying associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals would further our knowledge of mechanisms related to managing molecular damage that may be targeted to preserve physical resilience. To characterize expression patterns of genes responsible for the oxidative stress response, RNA was extracted and sequenced from skeletal muscle biopsies collected from 575 participants (≥70 years old) from the Study of Muscle, Mobility, and Aging.

Higher expression of denervation-responsive genes is negatively associated with muscle volume and performance traits in the study of muscle, mobility, and aging (SOMMA).

With aging skeletal muscle fibers undergo repeating cycles of denervation and reinnervation. In approximately the 8th decade of life reinnervation no longer keeps pace, resulting in the accumulation of persistently denervated muscle fibers that in turn cause an acceleration of muscle dysfunction. The significance of denervation in important clinical outcomes with aging is poorly studied.

Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures.

Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue.

An optimized approach to study nanoscale sarcomere structure utilizing super-resolution microscopy with nanobodies.

The sarcomere is the fundamental contractile unit in skeletal muscle, and the regularity of its structure is critical for function. Emerging data demonstrates that nanoscale changes to the regularity of sarcomere structure can affect the overall function of the protein dense ~2μm sarcomere. Further, sarcomere structure is implicated in many clinical conditions of muscle weakness.