Bioinformatic identification of genes suppressing genome instability

Unbiased forward genetic screens for mutations causing increased gross chromosomal rearrangement (GCR) rates in Saccharomyces cerevisiae are hampered by the difficulty in reliably using qualitative GCR assays to detect mutants with small but significantly increased GCR rates. We therefore developed a bioinformatic procedure using genome-wide functional genomics screens to identify and prioritize candidate GCR-suppressing genes on the basis of the shared drug sensitivity suppression and similar genetic interactions as known GCR suppressors. The number of known suppressors was increased from 75 to 110 by testing 87 predicted genes, which identified unanticipated pathways in this process. This analysis explicitly dealt with the lack of concordance among high-throughput datasets to increase the reliability of phenotypic predictions. Additionally, shared phenotypes in one assay were imperfect predictors for shared phenotypes in other assays, indicating that although genome-wide datasets can be useful in aggregate, caution and validation methods are required when deciphering biological functions via surrogate measures, including growth-based genetic interactions.     

Pharmacokinetic,pharmacodynamic and clinical evaluation of saxagliptin in type 2 diabetes

Introduction: Dipeptide peptidase-4 (DPP-4) inhibitors such as saxagliptin are established and efficacious oral therapies in the management of type 2 diabetes. These agents have the potential to confer significant benefits in glycemic control without the risk of weight gain and hypoglycemia, which may be associated with other medications used to treat type 2 diabetes.

Areas covered: This review examines the pharmacokinetics, efficacy and tolerability of saxagliptin for the management of type 2 diabetes.

Expert opinion: Saxagliptin is routinely used in the management of type 2 diabetes as monotherapy, and in combination with other oral agents and insulin. Robust clinical trials have shown consistent improvements in glycated hemoglobin, fasting and postprandial glucose levels, with few adverse effects. The agent is well tolerated with low rates of hypoglycemia in the absence of insulin or sulphonylurea therapy.     

“I felt like the angel of death”: role conflicts and moral distress among allied professionals employed by the US cardiovascular implantable electronic device industry

Purpose  

This study aimed to identify themes associated with role conflicts and moral distress experienced by cardiovascular implantable electronic device (CIED) industry-employed allied professionals (IEAPs) in the clinical setting.     

Spontaneous Coronary Artery Dissection

Spontaneous coronary artery dissection is an important etiology of nonatherosclerotic acute coronary syndrome, myocardial infarction, and sudden death. Innovations in the catheterization laboratory including optical coherence tomography and intravascular ultrasound have enhanced the ability to visualize intimal disruption and intramural hematoma associated with SCAD. Formerly considered “rare,” these technological advances and heightened awareness suggest that SCAD is more prevalent than prior estimates. SCAD is associated with female sex, young age, extreme emotional stress, or extreme exertion, pregnancy, and fibromuscular dysplasia. The clinical characteristics and management strategies of SCAD patients are different than for atherosclerotic heart disease and deserve specific consideration. This review will highlight recent discoveries about SCAD as well as describe current efforts to elucidate remaining gaps in knowledge.