Ischemia-Reperfusion Injury Leads to Distinct Temporal Cardiac Remodeling in Normal versus Diabetic Mice

Diabetes is associated with higher incidence of myocardial infarction (MI) and increased propensity for subsequent events post-MI. Here we conducted a temporal analysis of the influence of diabetes on cardiac dysfunction and remodeling after ischemia reperfusion (IR) injury in mice. Diabetes was induced using streptozotocin and IR performed by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for up to 42 days. We first evaluated changes in cardiac function using echocardiography after 24 hours reperfusion and observed IR injury significantly decreased the systolic function, such as ejection fraction, fractional shortening and end systolic left ventricular volume (LVESV) in both control and diabetic mice. The longitudinal systolic and diastolic strain rate were altered after IR, but there were no significant differences between diabetic mice and controls. However, a reduced ability to metabolize glucose was observed in the diabetic animals as determined by PET-CT scanning using 2-deoxy-2-(18F)fluoro-D-glucose. Interestingly, after 24 hours reperfusion diabetic mice showed a reduced infarct size and less apoptosis indicated by TUNEL analysis in heart sections. This may be explained by increased levels of autophagy detected in diabetic mice hearts. Similar increases in IR-induced macrophage infiltration detected by CD68 staining indicated no change in inflammation between control and diabetic mice. Over time, control mice subjected to IR developed mild left ventricular dilation whereas diabetic mice exhibited a decrease in both end diastolic left ventricular volume and LVESV with a decreased intraventricular space and thicker left ventricular wall, indicating concentric hypertrophy. This was associated with marked increases in fibrosis, indicted by Masson trichrome staining, of heart sections in diabetic IR group. In summary, we demonstrate that diabetes principally influences distinct IR-induced chronic changes in cardiac function and remodeling, while a smaller infarct size and elevated levels of autophagy with similar cardiac function are observed in acute phase

Cluster Analysis of Symptoms Among Patients with Upper Extremity Musculoskeletal Disorders

Introduction Some musculoskeletal disorders of the upper extremity are not readily classified. The study objective was to determine if there were symptom patterns in self-identified repetitive strain injury (RSI) patients. Methods Members (n = 700) of the Dutch RSI Patients Association filled out a detailed symptom questionnaire. Factor analysis followed by cluster analysis grouped correlated symptoms. Results Eight clusters, based largely on symptom severity and quality were formulated. All but one cluster showed diffuse symptoms; the exception was characterized by bilateral symptoms of stiffness and aching pain in the shoulder/neck. Conclusions Case definitions which localize upper extremity musculoskeletal disorders to a specific anatomical area may be incomplete. Future clustering studies should rely on both signs and symptoms. Data could be collected from health care providers prospectively to determine the possible prognostic value of the identified clusters with respect to natural history, chronicity, and return to work

A neuroscientist's guide to lipidomics

Nerve cells mould the lipid fabric of their membranes to ease vesicle fusion, regulate ion fluxes and create specialized microenvironments that contribute to cellular communication. The chemical diversity of membrane lipids controls protein traffic, facilitates recognition between cells and leads to the production of hundreds of molecules that carry information both within and across cells. With so many roles, it is no wonder that lipids make up half of the human brain in dry weight. The objective of neural lipidomics is to understand how these molecules work together; this difficult task will greatly benefit from technical advances that might enable the testing of emerging hypotheses