Background: Tonsillectomy is regularly performed in adults with acute tonsillitis, but with scarce evidence. A reduction in tonsillectomies has coincided with an increase in acute adult hospitalisation for tonsillitis complications. We aimed to assess the clinical effectiveness and cost-effectiveness of conservative management versus tonsillectomy in patients with recurrent acute tonsillitis.
View Article and Find Full Text PDFBackground: Vitamin D insufficiency is common in older people and may lead to increased bone resorption, bone loss, and increased falls and fractures. However, clinical trials assessing the effect of vitamin D supplementation on bone mineral density (BMD) have yielded conflicting results.
Objectives: This study examined the effect of vitamin D supplementation on BMD at the hip, using dual-energy X-ray absorptiometry.
Background: Repeated symptomatic urinary tract infections (UTIs) affect 25% of people who use clean intermittent self-catheterisation (CISC) to empty their bladder. We aimed to determine the benefits, harms, and cost-effectiveness of continuous low-dose antibiotic prophylaxis for prevention of recurrent UTIs in adult users of CISC.
Methods: In this randomised, open-label, superiority trial, we enrolled participants from 51 UK National Health Service organisations.
Introduction: The antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease (APPLE COPD-ICON2) trial is a prospective 2×2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) at high risk of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the required response in platelet function measured using the Multiplate test in patients with COPD.
Methods And Analysis: Patients with COPD are screened for eligibility using inclusion and exclusion criteria.
Background: People carrying out clean intermittent self-catheterisation (CISC) to empty their bladder often suffer repeated urinary tract infections (UTIs). Continuous once-daily, low-dose antibiotic treatment (antibiotic prophylaxis) is commonly advised but knowledge of its effectiveness is lacking.
Objective: To assess the benefit, harms and cost-effectiveness of antibiotic prophylaxis to prevent UTIs in people who perform CISC.
Background: Clean intermittent self-catheterisation is an important management option for people who cannot empty their bladder effectively. Recurrent urinary tract infections are common in these patients. Data from recent studies suggest that antibiotic prophylaxis may be beneficial in reducing infection risk, but the effectiveness of this intervention remains uncertain.
View Article and Find Full Text PDFBackground: Effects of small-particle long-acting β-agonists on the small airways have been poorly documented.
Objective: We used impulse oscillometry (IOS) to compare single and repeated dosing effects of small- and large-particle long-acting β-agonists.
Methods: After a 1- to 2-week run-in period, patients received either 12 μg of small-particle hydrofluoroalkane 134a-formoterol solution or 50 μg of large-particle salmeterol dry powder twice daily plus inhaled corticosteroid for 1 to 2 weeks with a 1- to 2-week washout period in between.
Glycogen is a primary form of energy storage in eukaryotes that is essential for glucose homeostasis. The glycogen polymer is synthesized from glucose through the cooperative action of glycogen synthase (GS), glycogenin (GN), and glycogen branching enzyme and forms particles that range in size from 10 to 290 nm. GS is regulated by allosteric activation upon glucose-6-phosphate binding and inactivation by phosphorylation on its N- and C-terminal regulatory tails.
View Article and Find Full Text PDFThe liver responds to an increase in blood glucose levels in the postprandial state by uptake of glucose and conversion to glycogen. Liver glycogen synthase (GYS2), a key enzyme in glycogen synthesis, is controlled by a complex interplay between the allosteric activator glucose-6-phosphate (G6P) and reversible phosphorylation through glycogen synthase kinase-3 and the glycogen-associated form of protein phosphatase 1. Here, we initially performed mutagenesis analysis and identified a key residue (Arg(582)) required for activation of GYS2 by G6P.
View Article and Find Full Text PDFInsulin rapidly suppresses hepatic glucose production and slowly decreases expression of genes encoding gluconeogenic proteins. In this study, we show that an immediate effect of insulin is to redirect newly synthesized glucose-6-phosphate to glycogen without changing the rate of gluconeogenesis. This process requires hepatic Akt2, as revealed by blunted insulin-mediated suppression of glycogenolysis in the perfused mouse liver, elevated hepatic glucose production during a euglycemic-hyperinsulinemic clamp, or diminished glycogen accumulation during clamp or refeeding in mice without hepatic Akt2.
View Article and Find Full Text PDFRecombinant muscle GYS1 (glycogen synthase 1) and recombinant liver GYS2 were phosphorylated by recombinant AMPK (AMP-activated protein kinase) in a time-dependent manner and to a similar stoichiometry. The phosphorylation site in GYS2 was identified as Ser7, which lies in a favourable consensus for phosphorylation by AMPK. Phosphorylation of GYS1 or GYS2 by AMPK led to enzyme inactivation by decreasing the affinity for both UDP-Glc (UDP-glucose) [assayed in the absence of Glc-6-P (glucose-6-phosphate)] and Glc-6-P (assayed at low UDP-Glc concentrations).
View Article and Find Full Text PDF