Background: Despite advances in ablation and other therapies for AF, progression of atrial fibrillation (AF) remains a significant clinical problem, associated with worse prognosis and worse treatment outcomes. Upstream therapies targeting inflammatory or antifibrotic mechanisms have been disappointing in preventing AF progression, but more recently genetic and genomic studies in AF suggest novel cellular and metabolic stress targets, supporting prior studies of lifestyle and risk factor modification (LRFM) for AF. However, while obesity is a significant risk factor, weight loss and risk factor modification have not been successfully applied in a US population with AF.
View Article and Find Full Text PDFAntioxid Redox Signal
December 2024
Alterations of mitochondrial bioenergetics and arginine metabolism are universally present and mechanistically linked to pulmonary arterial hypertension (PAH), but there is little knowledge of arginine metabolism and mitochondrial functions across the different pulmonary hypertension (PH) groups. We hypothesize that abnormalities in mitochondrial functions are present across all PH groups and associated with clinical phenotypes. We test the hypothesis in PH patients and healthy controls from the Pulmonary Vascular Disease Phenomics Program cohort, who had comprehensive clinical phenotyping and follow-up for at least 4 years for death or transplant status.
View Article and Find Full Text PDFGenome-wide association studies have identified a locus on chromosome 10q22, where many co-inherited single nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF). This study seeks to identify the impact of this locus on gene expression at the transcript isoform level in human left atria and to gain insight into potential causal variants. Bulk RNA sequencing was analyzed to identify myozenin 1 () and synaptopodin 2-like () transcript isoforms and the association of common SNPs in this region with transcript isoform expression levels.
View Article and Find Full Text PDFBackground: Atrial fibrillation GWAS (genome-wide association studies) identified significant associations for rs1152591 and linked variants in the gene encoding Nesprin-2, which connects the nuclear membrane with the cytoskeleton.
Methods: Reporter gene vector transfection and CRISPR-Cas9 editing were used to identify the causal variant regulating the expression of . After knockdown or overexpression in human stem cell-derived cardiomyocytes, nuclear phenotypes were assessed by imaging and atomic force microscopy.
We report the measurement of impulsive stimulated x-ray Raman scattering in neutral liquid water. An attosecond pulse drives the excitations of an electronic wavepacket in water molecules. The process comprises two steps: a transition to core-excited states near the oxygen atoms accompanied by transition to valence-excited states.
View Article and Find Full Text PDFGenomics allows identification of genes and mutations associated with amyotrophic lateral sclerosis (ALS). Mutations in annexin A11 (ANXA11) are responsible for ~1% of all familial ALS and fronto-temporal dementia cases. The present study used the fruit fly, , to assess the mechanism of toxicity of ANXA11 mutants in residues that are conserved in the fly ANXB11 protein, the closest homolog to human ANXA11.
View Article and Find Full Text PDFWearable electronics have become integral for monitoring physiological parameters in diverse applications, particularly in medical and military fields. e-Textiles, featuring integrated conductive threads or fabrics, offer seamless integration and comfort for prolonged contact with the body. Despite their potential, the biofouling of textile-based electrode systems by skin microbes remains a significant challenge, limiting their operational lifespan.
View Article and Find Full Text PDFMultifunctional vertically aligned nanocomposite (VAN) thin films exhibit considerable potential in diverse fields. Here, a BaTiO-FeCoNi alloy (BTO-FCN) system featuring an ultrathin ternary FCN alloy nanopillar array embedded in the BTO matrix has been developed with tailorable nanopillar size and interpillar distance. The magnetic alloy nanopillars combined with a ferroelectric oxide matrix present intriguing multifunctionality and coupling properties.
View Article and Find Full Text PDFIntroduction: Given the prevalence and staggering cost of neurological disorders, there is dire need for effective early detection and intervention tools. Emerging evidence suggests that multidisciplinary lifestyle interventions (MLI) may mitigate the risk and progression of neurological disorders. The objectives of this protocol are (1) to test the impact of MLI on the progression of neurological disorders and (2) to identify multi-omic biomarkers for early stages of neurological disease and the impact of MLIs on these biomarkers.
View Article and Find Full Text PDFAnnexin A11 mutations are a rare cause of amyotrophic lateral sclerosis (ALS), wherein replicated protein variants P36R, G38R, D40G and D40Y are located in a small-alpha helix within the long, disordered N-terminus. To elucidate disease mechanisms, we characterised the phenotypes induced by a genetic loss of function (LoF) and by misexpression of G38R and D40G in vivo. Loss of Annexin A11 results in a low-penetrant behavioural phenotype and aberrant axonal morphology in zebrafish homozygous knockout larvae, which is rescued by human WT Annexin A11.
View Article and Find Full Text PDFBackground: Palmitoylethanolamide (PEA) has analgesic/anti-inflammatory properties that may be a suitable alternative to over-the-counter (OTC) non-steroidal analgesics/anti-inflammatories. While OTC pain medications can impair strength training adaptations, the mechanism of action of PEA is distinct from these and it may not negatively affect skeletal muscle adaptations to strength training.
Methods: The primary aim of this study was to investigate the effects of daily PEA supplementation (350 mg Levagen + equivalent to 300 mg PEA) combined with 8-weeks of resistance training on lean body mass with secondary aims addressing strength, power, sleep, and wellbeing compared to placebo (PLA) in young, healthy, active adults.
Objective: To describe a structured, iterative, data-driven approach for modifying implementation strategies for a complex evidence-based practice during a nationwide scale-up initiative.
Data Sources And Study Setting: We scaled-up implementation of Critical Time Intervention (CTI)-an evidence-based case management model-across 32 diverse community-based Veterans Affairs (VA) "Grant and Per Diem" case management (GPD-CM) agencies that serve homeless-experienced Veterans transitioning to independent living. Primary data were collected using qualitative methods.
Purpose: Describe spirituality's role in a sample of Hispanic adolescent and young adult (AYA) cancer survivors.
Methods: This phenomenology-informed convergent parallel mixed-methods study aimed to explore participants' lived experiences with hope during cancer treatments and cancer survivorship. A purposive sample of Hispanic AYAs who completed cancer treatments 2-5 years ago were virtually recruited for participation.
Orthopedic device-related infection (ODRI) poses a significant threat to patients with titanium-based implants. The challenge lies in developing antibacterial surfaces that preserve the bulk mechanical properties of titanium implants while exhibiting characteristics similar to bone tissue. In response, we present a two-step approach: silver nanoparticle (AgNP) coating followed by selective laser-assisted surface alloying on commonly used titanium alumina vanadium (TiAl6V4) implant surfaces.
View Article and Find Full Text PDFNon-small cell lung cancer metastasis to skeletal muscle is an uncommon occurrence. Lung cancers are more likely to spread to the brain, bone, liver, and adrenals. Here, we present a rare case of non-small cell lung cancer metastasis to the skeletal muscle in a 54-year-old male.
View Article and Find Full Text PDFBackground And Objective: Male stress urinary incontinence (SUI) and erectile dysfunction (ED) are well established diagnoses within Men's Health, often more specifically within the prostate cancer survivorship cohort. Taken individually, well defined treatment algorithms exist with which many surgeons are comfortable; however, treatment of both in a single setting or staged fashion introduces complexity. Emerging treatment options also exist, and there is immature or minimal data when these are combined with inflatable penile prosthesis (IPP) insertion, radiation history, and/or variable degrees of incontinence.
View Article and Find Full Text PDFFragmented care delivery is a barrier to improving health system performance worldwide. Investment in meso-level organisations is a potential strategy to improve health system integration, however, its effectiveness remains unclear. In this paper, we provide an overview of key international and Australian integrated care policies.
View Article and Find Full Text PDFWe sought to assess the effects of repeated cold-water immersions (CWI) on respiratory, metabolic, and sympathoadrenal responses to graded exercise in hypoxia. Sixteen (2 female) participants (age: 21.2 ± 1.
View Article and Find Full Text PDFThis article is part of an American Board of Pediatrics Foundation-sponsored effort to analyze and forecast the pediatric subspecialty workforce between 2020 and 2040. Herein, an overview of the current pediatric gastroenterology workforce is provided, including demographics, work characteristics, and geographic distribution of practitioners. Brief context is provided on the changing nature of current practice models and the increasing prevalence of some commonly seen disorders.
View Article and Find Full Text PDFWhile the adsorption/bio-oxidation (A/B) process has been widely studied for carbon capture and shortcut nitrogen (N) removal, its integration with enhanced biological phosphorus (P) removal (EBPR) has been considered challenging and thus unexplored. Here, full-scale pilot testing with an integrated system combining A-stage high-rate activated sludge with B-stage partial (de)nitrification/anammox and side-stream EBPR (HRAS-P(D)N/A-S2EBPR) was conducted treating real municipal wastewater. The results demonstrated that, despite the relatively low influent carbon load, the B-stage P(D)N-S2EBPR system could achieve effective P removal performance, with the carbon supplement and redirection of the A-stage sludge fermentate to the S2EBPR.
View Article and Find Full Text PDFInsufficient sleep is a growing global problem, with poor sleep associated with many negative health and performance outcomes. Previous reviews investigating the effect of diet on sleep have highlighted the amino acid tryptophan as a promising sleep-promoting nutrient, with the richest food source of tryptophan, ⍺-lactalbumin, requiring further investigation. Therefore, this systematic review aimed to review the existing evidence of association between ⍺-lactalbumin and sleep.
View Article and Find Full Text PDFA specific genetic variant associated with atrial fibrillation risk, rs17171731, was identified as a regulatory variant responsible for controlling expression. The atrial fibrillation risk allele decreases expression, whose knockdown alters the expression of many genes in stem cell-derived cardiomyocytes, including , and led to pro-arrhythmogenic changes in the late sodium current and Ca cycling. knockout mice had increased P-wave and QT interval duration and were more susceptible to pacing-induced arrhythmias vs control mice.
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