Thomassenenevoldsen1672

Epigenetic clocks use DNA methylation to estimate biological age. Whether body composition and physical activity are associated with these clocks is not well understood. Using blood samples collected at enrollment (2003-2009) from 2,758 women in the US nationwide Sister Study, we calculated 6 epigenetic age acceleration metrics using 4 epigenetic clocks (Hannum, Horvath, PhenoAge, GrimAge). Recreational physical activity was self-reported, and adiposity measures were assessed by trained medical examiners (body mass index (BMI), waist-to-hip ratio (WtH), waist circumference). In cross-sectional analyses, all adiposity measures were associated with epigenetic age acceleration. The strongest association was for BMI and PhenoAge, a measure of biological age that correlates with chronic disease (BMI of ≥35.0 vs. 18.5-24.9, β = 3.15 years, 95% confidence interval (CI) 2.41, 3.90; P for trend less then 0.001). In a mutual-adjustment model, both were associated with PhenoAge age acceleration (BMI of ≥35.0 vs. 18.5-24.9, β = 2.69 years, 95% CI 1.90, 3.48; P for trend less then 0.001; quartile 4 vs.1 WtH, β = 1.00 years, 95% CI 0.34, 1.65; P for trend less then 0.008). After adjustment, physical activity was associated only with GrimAge (quartile 4 vs. 1, β = -0.42 years, 95% CI -0.70, -0.14; P for trend = 0.001). Physical activity attenuated the waist circumference associations with PhenoAge and GrimAge. Excess adiposity was associated with epigenetic age acceleration; physical activity might attenuate associations with waist circumference.

While Pseudomonas aeruginosa (Pa) eradication regimens have contributed to a decline in Pa prevalence in people with cystic fibrosis (CF), this antibiotic exposure might increase the risk of acquisition of drug-resistant organisms. This study evaluated the association between antipseudomonal antibiotic exposure intensity and acquisition risk of drug-resistant organisms among children with CF and new Pa infection.

We utilized data from the Early Pseudomonas Infection Control Clinical Trial (EPIC CT), a randomized controlled trial comparing Pa eradication strategies in children with CF and new Pa. The exposure was the number of weeks of oral or inhaled antipseudomonal antibiotics, or ever vs. never treatment with intravenous antipseudomonal antibiotics, during the 18 months of EPIC CT participation. The primary outcomes were risks of acquisition of several respiratory organisms during five years of follow up after EPIC CT estimated using Cox proportional hazards models separately for each specific organism.

Among 249 participants, there was no increased acquisition risk of any organism associated with greater inhaled antibiotic exposure. With each additional week of oral antibiotics, there was an increased hazard of Achromobacter xylosoxidans acquisition (HR=1.24, 95% CI 1.02-1.50; p=0.03). Treatment with intravenous antibiotics was associated with an increased hazard of acquisition of multidrug-resistant Pa (HR=2.47; 95% CI 1.28-4.78; p=0.01) and MRSA (HR=1.57; 95% CI 1.03-2.40); p=0.04).

Results from this study illustrate the importance of making careful antibiotic choices to balance the benefits of antibiotics in people with CF while minimizing the risk of acquisition of drug-resistant organisms.

Results from this study illustrate the importance of making careful antibiotic choices to balance the benefits of antibiotics in people with CF while minimizing the risk of acquisition of drug-resistant organisms.

Palpitations, particularly common in women, are generally considered benign symptoms rarely caused by clinically important arrhythmias. Nevertheless, palpitations may cause anxiety, depression, and decreased health-related quality of life (HRQOL). This study investigates to what degree palpitations cause symptoms such as anxiety and depression and affect HRQOL in women and whether direct feedback of underlying heart rhythm during palpitations decrease anxiety and depression and increase HRQOL in women.

The study included 821 women, age 21-88 years (mean 57 ± 11 years), with symptomatic palpitations recruited using social media. For 60 days, the participants used a handheld electrocardiogram (ECG)-recording device (Coala Heart Monitor) connected to their smartphones. ECG was recorded twice a day and when symptoms were present and was automatically algorithm-interpreted with immediate response to the user. Selleck Ruxotemitide Non-benign arrhythmias were also analysed manually. Questionnaires addressing anxiety and depression-Hospital Anxiety and Depression Scale (HADS), Generalized Anxiety Disorder (GAD-7), HRQOL (RAND-36), and Symptoms Checklist Frequency and Severity (SCL)-were analysed before and after the data were collected. A total of 101 804 ECG recordings were automatically analysed. In 94%, sinus rhythm or premature atrial/ventricular contraction were recorded; in 6%, atrial fibrillation or supraventricular tachycardia were recorded. Apart from premature ventricular contractions, no ventricular arrhythmias were documented. Anxiety and depression (HADS and GAD-7) decreased (P < 0.001) as did frequency and severity of symptoms, and HRQOL increased in all domains (P < 0.001) at the 2-month follow-up.

Instant analysis of the ECG with direct response during palpitations decreases symptoms, anxiety, and depression and increases HRQOL in women.

Instant analysis of the ECG with direct response during palpitations decreases symptoms, anxiety, and depression and increases HRQOL in women.The thyroid-stimulating hormone receptor (TSHR) is a G-protein-coupled receptor group A family member with 7 transmembrane helices. We generated 3 new models of its entire transmembrane region using a 600 ns molecular simulation. The simulation started from our previously published model, which we have now revised by also modeling the intracellular loops and the C-terminal tail, adding internal waters and embedding it into a lipid bilayer with a water layer and with ions added to complete the system. We have named this model TSHR-TMD-TRIO since 3 representative dominant structures were then extracted from the simulation trajectory and compared with the original model. These structures each showed small but significant changes in the relative positions of the helices. The 3 models were also used as targets to dock a set of small molecules that are known active compounds including a new TSHR antagonist (BT362), which confirmed the appropriateness of the model with some small molecules showing significant preference for one or other of the structures.