Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous glucagon-like peptide-1 (GLP-1). We hypothesized that genetic variation in the gene encoding the GLP-1 receptor (GLP1R) could affect the metabolic response to DPP-4 inhibition. To evaluate the relationship between the GLP1R rs6923761 variant (G-to-A nucleic acid substitution) and metabolic responses, we performed mixed meal studies in individuals with type 2 diabetes mellitus and hypertension after 7-day treatment with placebo and the DPP-4 inhibitor sitagliptin. selleckchem This analysis is a substudy of NCT02130687. The genotype frequency was 13127 GGGAAA among individuals of European ancestry. Postprandial glucose excursion was significantly decreased in individuals carrying the rs6923761 variant (GA or AA) as compared with GG individuals during both placebo (P = 0.001) and sitagliptin treatment (P = 0.045), while intact GLP-1 levels were similar among the genotype groups. In contrast, sitagliptin lowered postprandial glucose to a greater degree in GG as compared with GA/AA individuals (P = 0.035). The relationship between GLP1R rs6923761 genotype and therapies that modulate GLP-1 signalling merits study in large populations.High-risk transcatheter procedures requiring hemodynamic support are growing and require multiple vascular access that may be challenging in cases of peripheral artery disease or lack of radial access and exposure to a higher risk of vascular complications. We report the novel utilization of a Y-shaped arterial extracorporeal membrane oxygenation (ECMO) cannula used as a single femoral access to perform percutaneous coronary intervention (PCI) and aortography during high-risk transcatheter aortic valve replacement (TAVR). The utilization of this 2-in-1 ECMO cannula may simplify vascular access and reduce vascular and bleeding complications during high-risk ECMO-supported transcatheter procedures.

Insulin glargine 300 U/mL (Gla-300) contains the same units versus glargine 100 U/mL (Gla-100) in three-fold lower volume, and higher subcutaneous (SC) doses are required in people with diabetes. To investigate blood glucose (BG) lowering potency, Gla-300 and Gla-100 were compared after intravenous (IV, for 4 h) and SC (for 24 h) injection in healthy Beagle dogs.

The dose of 0.15 U/kg Gla-300 and Gla-100 was injected IV in 12 dogs. BG, C-peptide, glucagon and the active metabolite 21A-Gly-human insulin (M1; liquid chromatography-tandem mass spectrometry method) were measured. Twelve other dogs were studied after SC injection of 0.3 U/kg Gla-300 and Gla-100.

After IV injection, Gla-300 and Gla-100 were equally potent [BG_AUC

ratio 1.01 (95% confidence interval, 0.94; 1.09)]. After SC injection, BG decreased slower and less with Gla-300. Similar metabolism of Gla-300 and Gla-100 to M1 occurred with IV dosing [M1_AUC

ratio 0.99 (95% confidence interval, 0.82; 1.22)], but with SC dosing M1_C

and AUC

were 44% and 17% lower; mean residency time and bioavailability were 32% longer and 50% lower, with Gla-300.

IV Gla-300 and Gla-100 have the equivalent of BG-lowering potency and M1 metabolism. SC Gla-300 has lower M1 bioavailability with a reduced BG-lowering effect and need for greater doses versus Gla-100.

IV Gla-300 and Gla-100 have the equivalent of BG-lowering potency and M1 metabolism. SC Gla-300 has lower M1 bioavailability with a reduced BG-lowering effect and need for greater doses versus Gla-100.Lipedema is a painful, underdiagnosed adipose tissue disorder, characterized by symmetrical swelling of the extremities due to subcutaneous fat deposition in the buttocks, thighs, legs, and arms, sparing the most distal part of the extremities. Although etiology and pathogenesis of lipedema is unclear, possible role of hormonal and genetic factors have been proposed previously. Patients with lipedema suffer from pain, easy bruising, tenderness, and disfigurement. Pain is the leading symptom in lipedema. Since the pain is associated with depression and impaired quality of life, reduction of pain is the major therapeutic approach. Pain in lipedema is attributed to allodynia, exaggerated sympathetic signaling, and estrogens. Although the mechanism of pain in lipedema is uncertain, effective treatment of lipedema should provide a satisfactory pain reduction. Efficacy of the conservative treatment is a matter of debate. Microcannular tumescent liposuction is the most effective therapeutic option for lipedema. There is a large body of evidence that this procedure significantly reduces pain in patients with lipedema.Clinicians regularly work as teams and perform joint actions that have a great deal of moral significance. As a result, clinicians regularly share moral responsibility for the actions of their teams and other clinicians. In this paper, we argue that clinicians are exceptionally susceptible to a special type of moral luck, called interpersonal moral luck, because their moral statuses are often affected by the actions of other clinicians in a way that is not fully within their control. We then argue that this susceptibility partly explains why a conscientious clinician has reason to avoid participating in unvirtuous healthcare teams. We also argue that this susceptibility partly explains the special systems of entitlements that characterize healthcare teams and set healthcare teams apart from other teams of workers.The d- and l-forms of lactate are important fermentation metabolites produced by intestinal bacteria but are found to negatively affect mucosal barrier function and human health. Both enantiomers of lactate can be converted with acetate into the presumed beneficial butyrate by a phylogenetically related group of anaerobes, including Anaerobutyricum and Anaerostipes spp. This is a low energy yielding process with a partially unknown pathway in Anaerobutyricum and Anaerostipes spp. and hence, we sought to address this via a comparative genomics, proteomics and physiology approach. We compared growth of Anaerobutyricum soehngenii on lactate with that on sucrose and sorbitol. Comparative proteomics revealed complete pathway of butyrate formation from sucrose, sorbitol and lactate. Notably, a gene cluster, lctABCDEF was abundantly expressed when grown on lactate. This gene cluster encodes a lactate dehydrogenase (lctD), electron transport proteins A and B (lctCB), nickel-dependent racemase (lctE), lactate permease (lctF) and short-chain acyl-CoA dehydrogenase (lctG).