Does Concomitant CABG Influence the Outcomes of Post-Myocardial Infarction Ventricular Septal Defect Repair?

Introduction: Ventricular septal defect (VSD) following myocardial infarction (MI) is a relatively infrequent complication with high mortality. Over time, understanding of the pathology and its management has resulted in improved outcomes; however, controversies remain. Objective: We sought to investigate the effect of concomitant coronary artery bypass graft (CABG) on outcomes following post-MI VSD repair. Methods: Electronic search was performed to identify all relevant studies published from 2000 to 2018. After assessment for inclusion and exclusion criteria, 66 studies were selected for the analysis. Data were extracted and pooled for systematic review and meta-analysis. Results: Average age was 68.7 years (95% CI 67.3-70.1) with 57% (95% CI 54-60) males. Coronary angiogram was available preoperatively in 94% (95% CI 92-96) of patients. Single-vessel disease was most common (47%, 95% CI 42-52) with left anterior descending coronary artery the most commonly involved vessel (55%, 95% CI 46-63). Concomitant CABG was performed in 52% (95% CI 46-57) of patients. Of these, infarcted territory was revascularized in 54% (95% CI 23-82). No significant survival difference was observed between those who had concomitant CABG versus those without CABG at 30 days (65%, 95% CI 58-72) vs (60%, 95% CI 47-72), 1 year (59%, 95% CI 50-68) vs (51%, 95% CI 41-61), and 5 years (46%, 95% CI 38-54) vs (39%, 95% CI 27-52) respectively. Discussion: Overall, concomitant CABG did not have a significant effect on survival following VSD repair, therefore, decision on revascularization should be weighed against the risks associated with prolonged cardiopulmonary bypass

Modelling the coupling between intracellular calcium release and the cell cycle during cortical brain development

Most neocortical neurons formed during embryonic brain development arise from radial glial cells which communicate, in part, via ATP mediated calcium signals. Although the intercellular signalling mechanisms that regulate radial glia proliferation are not well understood, it has recently been demonstrated that ATP dependent intracellular calcium release leads to an increase of nearly 100% in overall cellular proliferation. It has been hypothesised that cytoplasmic calcium accelerates entry into S phase of the cell cycle and/or acts to recruit otherwise quiescent cells onto the cell cycle. In this paper we study this cell cycle acceleration and recruitment by forming a differential equation model for ATP mediated calcium-cell cycle coupling via Cyclin D in a single radial glial cell. Bifurcation analysis and numerical simulations suggest that the cell cycle period depends only weakly on cytoplasmic calcium. Therefore the accelerative impact of calcium on the cell cycle can only account for a small fraction of the large increase in proliferation observed experimentally. Crucially however, our bifurcation analysis reveals that stable fixed point and stable limit cycle solutions can coexist, and that calcium dependent Cyclin D dynamics extend the oscillatory region to lower Cyclin D synthesis rates, thus rendering cells more susceptible to cycling. This supports the hypothesis that cycling glial cells recruit quiescent cells (in G0 phase) onto the cell cycle, via a calcium signalling mechanism, and that this may be the primary means by which calcium augments proliferation rates at the population scale. Numerical simulations of two coupled cells demonstrate that such a scenario is indeed feasibl

A Novel 3-Hydroxysteroid Dehydrogenase That Regulates Reproductive Development and Longevity

A multidisciplinary approach identifies novel biochemical activities involved in the synthesisof C. elegans bile acid-like steroids, which act as hormones that regulate sterol metabolism and longevity

Hepatic FXR/SHP axis modulates systemic glucose and fatty acid homeostasis in aged mice

The nuclear receptors farnesoid X receptor (FXR; NR1H4) and small heterodimer partner (SHP; NR0B2) play crucial roles in bile acid homeostasis. Global double knockout of FXR and SHP signaling (DKO) causes severe cholestasis and liver injury at early ages. Here, we report an unexpected beneficial impact on glucose and fatty acid metabolism in aged DKO mice, which show suppressed body weight gain and adiposity when maintained on normal chow. This phenotype was not observed in single Fxr or Shp knockouts. Liver-specific Fxr/Shp double knockout mice fully phenocopied the DKO mice, with lower hepatic triglyceride accumulation, improved glucose/insulin tolerance, and accelerated fatty acid use. In both DKO and liver-specific Fxr/Shp double knockout livers, these metabolic phenotypes were associated with altered expression of fatty acid metabolism and autophagy-machinery genes. Loss of the hepatic FXR/SHP axis reprogrammed white and brown adipose tissue gene expression to boost fatty acid usage.ConclusionCombined deletion of the hepatic FXR/SHP axis improves glucose/fatty acid homeostasis in aged mice, reversing the aging phenotype of body weight gain, increased adiposity, and glucose/insulin tolerance, suggesting a central role of this axis in whole-body energy homeostasis. (Hepatology 2017;66:498-509)