Embedding physical activity in the heart of the NHS: the need for a whole-system approach

Solutions to the global challenge of physical inactivity have tended to focus on interventions at an individual level, when evidence shows that wider factors, including the social and physical environment, play a major part in influencing health-related behaviour. A multidisciplinary perspective is needed to rewrite the research agenda on physical activity if population-level public health benefits are to be demonstrated. This article explores the questions that this raises regarding the particular role that the UK National Health Service (NHS) plays in the system. The National Centre for Sport and Exercise Medicine in Sheffield is put forward as a case study to discuss some of the ways in which health systems can work in collaboration with other partners to develop environments and systems that promote active lives for patients and staff

Two Distinct Mechanisms for Actin Capping Protein Regulation—Steric and Allosteric Inhibition

A crystallographic study reveals the structural basis for regulation by two different inhibitors of the actin capping protein, a critical factor controlling actin-driven cell motility

Electrotonic Coupling between Human Atrial Myocytes and Fibroblasts Alters Myocyte Excitability and Repolarization

Atrial fibrosis has been implicated in the development and maintenance of atrial arrhythmias, and is characterized by expansion of the extracellular matrix and an increased number of fibroblasts (Fbs). Electrotonic coupling between atrial myocytes and Fbs may contribute to the formation of an arrhythmogenic substrate. However, the role of these cell-cell interactions in the function of both normal and diseased atria remains poorly understood. The goal of this study was to gain mechanistic insight into the role of electrotonic Fb-myocyte coupling on myocyte excitability and repolarization. To represent the system, a human atrial myocyte (hAM) coupled to a variable number of Fbs, we employed a new ionic model of the hAM, and a variety of membrane representations for atrial Fbs. Simulations elucidated the effects of altering the intercellular coupling conductance, electrophysiological Fb properties, and stimulation rate on the myocyte action potential. The results demonstrate that the myocyte resting potential and action potential waveform are modulated strongly by the properties and number of coupled Fbs, the degree of coupling, and the pacing frequency. Our model provides mechanistic insight into the consequences of heterologous cell coupling on hAM electrophysiology, and can be extended to evaluate these implications at both tissue and organ levels

Association between left ventricular global longitudinal strain, health-related quality of life and functional capacity in chronic kidney disease patients with preserved ejection fraction

Aim: Patients with chronic kidney disease (CKD) have a significant burden of dyspnoea and fatigue in spite having normal left ventricular (LV) ejection fraction (EF). Global longitudinal strain (GLS) can detect subtle changes in LV function. This study aimed to evaluate the relationship between LV function, functional capacity and quality of life (QOL) in CKD patients with preserved EF. Methods: A cross-sectional study of patients with stage 3/4 CKD (n = 108). Clinical characteristics, biochemical data, functional capacity (6-min walk test (6MWT), timed up and go (TUG) test) and QOL (short form-12 (SF12v2™) ) were measured. Echocardiogram was used to assess GLS, EF and diastolic function (E/A, e’ and E/e’). Results: The mean age was 58.1 ± 9.9 years, 55.6% were men, estimated glomerular filtration rate was 44.8 ± 10.6 mL/min/1.73 m2 , GLS was −18.5 ± 3.6% and 19.4% had impaired GLS ( > −16%). Patients with impaired GLS had a significantly shorter 6MWT and slower TUG test compared with patients with preserved GLS. Bivariate analysis showed GLS and E/e’ correlated with distance walked in 6MWT (GLS (r = −0.24, P = 0.02); E/e’(r = −0.38, P = 0.002) ). Following adjustment for potential confounders, GLS remained independently associated with 6MWT (model R2 = 0.37, P < 0.001). Mean physical component summary scores (PCS) and mental component summary scores (MCS) were 43.0 ± 10.2 and 50.9 ± 9.5. There was no cardiac parameter that was independently associated with PCS. However women, lower systolic blood pressure and GLS was associated with lower MCS (model R2 = 0.30, P < 0.001). Conclusion: GLS was associated with measures of functional capacity and QOL in CKD patients with preserved EF

Quantitative structure-activity relationship (QSAR) of indoloacetamides as inhibitors of human isoprenylcysteine carboxyl methyltransferase

10.1016/j.bmcl.2006.11.030Bioorganic and Medicinal Chemistry Letters1741025-1032BMCL