Regional Variation in RBM20 Causes a Highly Penetrant Arrhythmogenic Cardiomyopathy.

Background Variants in the cardiomyocyte-specific RNA splicing factor RBM20 have been linked to familial cardiomyopathy, but the causative genetic architecture and clinical consequences of this disease are incompletely defined. Methods and Results To define the genetic architecture of RBM20 cardiomyopathy, we first established a database of RBM20 variants associated with cardiomyopathy and compared these to variants observed in the general population with respect to their location in the RBM20 coding transcript. We identified 2 regions significantly enriched for cardiomyopathy-associated variants in exons 9 and 11.

Exercise-induced hypoalgesia: Pain tolerance, preference and tolerance for exercise intensity, and physiological correlates following dynamic circuit resistance exercise.

Previous research has demonstrated significant decreases in pain perception in healthy individuals following both aerobic and upper body resistance exercise, but research on circuit training has been limited. The purpose of the study was to determine the effects of a strenuous bout of dynamic circuit resistance exercise on pain threshold and pain tolerance in conjunction with changes in blood lactate levels, heart rate (HR), and perceived exertion. A sample of 24 college-age students participated in 2 sessions: (1) a maximal strength testing session and (2) a circuit training bout of exercise that consisted of 3 sets of 12 repetitions with a 1:1 work to rest ratio at 60% one-repetition maximum (1-RM) predicted from a three-repetition maximum (3-RM) for 9 exercises.

Use, knowledge, and attitudes toward evidence-based practice among nursing staff.

Background: Little information is known about the use, knowledge, and attitudes toward evidence-based practice (EBP) among nurses in a large academic hospital. This cross-sectional, descriptive study examined the knowledge, attitudes, and use of EBP by nurses at a large academic, Magnet(®)-designated medical center.

Methods: Data were collected from 593 nurses who completed the Clinical Effectiveness and Evidence Based Practice Questionnaire between November 2011 and March 2012.

De novo fragment design: a medicinal chemistry approach to fragment-based lead generation.

The use of fragments with low binding affinity for their targets as starting points has received much attention recently. Screening of fragment libraries has been the most common method to find attractive starting points. Herein, we describe a unique, alternative approach to generating fragment leads.

Discovery of a novel series of 4-quinolone JNK inhibitors.

A novel series of highly selective JNK inhibitors based on the 4-quinolone scaffold was designed and synthesized. Structure based drug design was utilized to guide the compound design as well as improvements in the physicochemical properties of the series. Compound (13c) has an IC(50) of 62/170 nM for JNK1/2, excellent kinase selectivity and impressive efficacy in a rodent asthma model.