Effects of population-based screening for atrial fibrillation on quality of life.

Background: Screening for atrial fibrillation is rising and may worsen or improve quality of life.

Methods: We assessed quality of life (EQ-5D-5L) data in 6,004 participants with stroke risk factors randomised to usual care (n=4,503) or implantable loop recorder with anticoagulation upon detection of atrial fibrillation (n=1,501). Five domains (mobility, selfcare, usual activities, pain/discomfort, anxiety/depression) each scored from one to five were calculated into individual index scores (worst=-0.

Prescription drug use in Danish children and adolescents 2005-2023.

Continuous monitoring of pediatric drug utilization is important for ensuring rational use and prioritizing research. This study provides an overview of pediatric prescription drug use among Danish children and adolescents from 2005-2023. Using Danish nationwide individual-level dispensing data, we identified all redeemed prescriptions for individuals < 18 years from January 2005-December 2023.

Psychological Impact of Presymptomatic X-Linked ALD Diagnosis and Surveillance: A Small Qualitative Study of Patient and Parent Experiences.

X-linked adrenoleukodystrophy (ALD) is a rare metabolic disorder. Symptoms range from cerebral demyelination (cALD) to adrenal insufficiency and slowly progressive myeloneuropathy. cALD is fatal if not treated with hematopoietic cell transplantation in the early stages of the disease course.

Unknown roles of tau pathology in neurological disorders. Challenges and new perspectives.

Aging presents progressive changes that increase the susceptibility of the central nervous system (CNS) to suffer neurological disorders (NDs). Several studies have reported that an aged brain suffering from NDs shows the presence of pathological forms of tau protein, a microtubule accessory protein (MAP) critical for neuronal function. In this context, accumulative evidence has shown a pivotal contribution of pathological forms of tau to Alzheimer's disease (AD) and tauopathies.

Face and content validity of the EMPOWER-UP questionnaire: a generic measure of empowerment in relational decision-making and problem-solving.

Background: Decision-making and problem-solving processes are powerful activities occurring daily across all healthcare settings. Their empowering potential is seldom fully exploited, and they may even be perceived as disempowering. We developed the EMPOWER-UP questionnaire to enable assessment of healthcare users' perception of empowerment across health conditions, healthcare settings, and healthcare providers' professional backgrounds.

Effects of atrial fibrillation screening according to thyroid function: Post-hoc analysis of the randomized LOOP study.

Purpose: Subclinical thyroid dysfunction is a marker for atrial fibrillation (AF) and stroke risk. This study explored the effects of AF screening according to thyroid-stimulating hormone (TSH) levels.

Methods: An AF screening trial (the LOOP study) was analyzed post-hoc according to baseline TSH.

Heart Failure Events After Long-term Continuous Screening for Atrial Fibrillation: Results From the Randomized LOOP Study.

Background: Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown.

Methods: The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in older individuals with additional stroke risk factors.

Rare and Common Genetic Variation Underlying Atrial Fibrillation Risk.

Importance: Atrial fibrillation (AF) has a substantial genetic component. The importance of polygenic risk is well established, while the contribution of rare variants to disease risk warrants characterization in large cohorts.

Objective: To identify rare predicted loss-of-function (pLOF) variants associated with AF and elucidate their role in risk of AF, cardiomyopathy (CM), and heart failure (HF) in combination with a polygenic risk score (PRS).

Proteomics couples electrical remodelling to inflammation in a murine model of heart failure with sinus node dysfunction.

Aims: In patients with heart failure (HF), concomitant sinus node dysfunction (SND) is an important predictor of mortality, yet its molecular underpinnings are poorly understood. Using proteomics, this study aimed to dissect the protein and phosphorylation remodelling within the sinus node in an animal model of HF with concurrent SND.

Methods And Results: We acquired deep sinus node proteomes and phosphoproteomes in mice with heart failure and SND and report extensive remodelling.

Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis.

We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism.

Atrial fibrillation: age at diagnosis, incident cardiovascular events, and mortality.

Background And Aims: Patients with atrial fibrillation (AF) are at increased risks of cardiovascular diseases and mortality, but risks according to age at diagnosis have not been reported. This study investigated age-specific risks of outcomes among patients with AF and the background population.

Methods: This nationwide population-based cohort study included patients with AF and controls without outcomes by the application of exposure density matching on the basis of sex, year of birth, and index date.

Mitochondria-tau association promotes cognitive decline and hippocampal bioenergetic deficits during the aging.

Current studies indicate that pathological modifications of tau are associated with mitochondrial dysfunction, synaptic failure, and cognitive decline in neurological disorders and aging. We previously showed that caspase-3 cleaved tau, a relevant tau form in Alzheimer's disease (AD), affects mitochondrial bioenergetics, dynamics and synaptic plasticity by the opening of mitochondrial permeability transition pore (mPTP). Also, genetic ablation of tau promotes mitochondrial function boost and increased cognitive capacities in aging mice.

Loss of Cardiac Splicing Regulator Is Associated With Early-Onset Atrial Fibrillation.

We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 in 2 independent cohorts. In a rat model with loss of , we demonstrated altered splicing of sarcomere genes (, , , and ), and differential expression in key cardiac genes. We identified altered sarcomere and mitochondrial structure on electron microscopy imaging and found compromised mitochondrial function.

Systemic inflammation activates coagulation and immune cell infiltration pathways in brains with propagating α-synuclein fibril aggregates.

Synucleinopathies are a group of diseases characterized by brain aggregates of α-synuclein (α-syn). The gradual accumulation of α-syn and the role of inflammation in early-stage pathogenesis remain poorly understood. We explored this interaction by inducing chronic inflammation in a common pre-clinical synucleinopathy mouse model.