Reesrollins9621
Racial and ethnic minorities in the United States report higher levels of both clinical and experimental pain, yet frequently receive inadequate pain treatment. Although these disparities are well documented, their underlying causes remain largely unknown. Evidence from social psychological and health disparities research suggests that clinician-patient racial/ethnic concordance may improve minority patient health outcomes. Yet whether clinician-patient racial/ethnic concordance influences pain remains poorly understood.
Medical trainees and community members/undergraduates played the role of "clinicians" and "patients," respectively, in simulated clinical interactions. All participants identified as non-Hispanic Black/African American, Hispanic white, or non-Hispanic white. Interactions were randomized to be either racially/ethnically concordant or discordant in a 3 (clinician race/ethnicity) × 2 (clinician-patient racial/ethnic concordance) factorial design. Clinicians took the medical history and vitalng minority, particularly non-Hispanic Black/African American, physician numbers may help reduce persistent racial/ethnic pain disparities.Membrane proteins (MPs) are the gatekeepers between different biological compartments separated by lipid bilayers. Being receptors, channels, transporters, or primary pumps, they fulfill a wide variety of cellular functions and their importance is reflected in the increasing number of drugs that target MPs. Functional studies of MPs within a native cellular context, however, is difficult due to the innate complexity of the densely packed membranes. Over the past decades, detergent-based extraction and purification of MPs and their reconstitution into lipid mimetic systems has been a very powerful tool to simplify the experimental system. In this review, we focus on proteoliposomes that have become an indispensable experimental system for enzymes with a vectorial function, including many of the here described energy transducing MPs. We first address long standing questions on the difficulty of successful reconstitution and controlled orientation of MPs into liposomes. A special emphasis is given on coreconstitution of several MPs into the same bilayer. Second, we discuss recent progress in the development of fluorescent dyes that offer sensitive detection with high temporal resolution. Finally, we briefly cover the use of giant unilamellar vesicles for the investigation of complex enzymatic cascades, a very promising experimental tool considering our increasing knowledge of the interplay of different cellular components.
Yellow fever (YF) is a rare viral disease that can be prevented through receipt of a live attenuated vaccine. In the US military, service members must receive the YF vaccine before assignment to endemic areas, putting active duty service women at heightened risk for inadvertent exposure during preconception or pregnancy. Few studies have investigated the safety of YF vaccination in pregnancy to date, and none in a military population.
Department of Defense Birth and Infant Health Research program data were used to identify pregnancies and infants among active duty US military women, 2003-2014. Multivariable regression models estimated associations with YF vaccine exposure during preconception/pregnancy and adverse outcomes (e.g. spontaneous abortion, birth defects). Sensitivity analyses were performed that excluded pregnancies exposed to other live vaccines. For analyses of birth defects only, a secondary sensitivity analysis was performed that excluded infants diagnosed with chromosomal anomalies.
Of tn. A tenuous association between preconception YF vaccine exposure and birth defects was observed in sensitivity analyses, which may warrant further investigation.
Insulin resistance (IR) is a risk factor for type 2 diabetes, diabetic kidney disease, cardiovascular disease and nonalcoholic steatohepatitis. Biliopancreatic diversion (BPD) is the most effective form of bariatric surgery for improving insulin sensitivity.
To identify plasma proteins correlating with the early restoration of insulin sensitivity after BPD.
Prospective single-center study including 20 insulin-resistant men with morbid obesity scheduled for BPD. Patient characteristics and blood samples were repeatedly collected from baseline up to 4 weeks postsurgery. IR was assessed by homeostatic model assessment for insulin resistance (HOMA-IR), Matsuda Index, and by studying metabolic profiles during meal tolerance tests. Unbiased proteomic analysis was performed to identify plasma proteins altered by BPD. Detailed plasma profiles were made on a selected set of proteins by targeted multiple reaction monitoring mass spectrometry (MRM/MS). Changes in plasma proteome were evaluated in relation to metabolic and inflammatory changes.
BPD resulted in improved insulin sensitivity and reduced body weight. Proteomic analysis identified 29 proteins that changed following BPD. Changes in plasma levels of afamin, apolipoprotein A-IV (ApoA4), and apolipoprotein A-II (ApoA2) correlated significantly with changes in IR.
Circulating levels of afamin, ApoA4, and ApoA2 were associated with and may contribute to the rapid improvement in insulin sensitivity after BPD.
Circulating levels of afamin, ApoA4, and ApoA2 were associated with and may contribute to the rapid improvement in insulin sensitivity after BPD.The pseudokinase (PK) RNase L is a functional ribonuclease and plays important roles in human innate immunity. The ribonuclease activity of RNase L can be regulated by the kinase inhibitor sunitinib. The combined use of oncolytic virus and sunitinib has been shown to exert synergistic effects in anticancer therapy. In this study, we aimed to uncover the mechanism of action through which sunitinib inhibits RNase L. anti-PD-1 inhibitor We solved the crystal structures of RNase L in complex with sunitinib and its analogs toceranib and SU11652. Our results showed that sunitinib bound to the ATP-binding pocket of RNase L. Unexpectedly, the αA helix linking the ankyrin repeat-domain and the PK domain affected the binding mode of sunitinib and resulted in an unusual flipped orientation relative to other structures in PDB. Molecular dynamics simulations and dynamic light scattering results support that the binding of sunitinib in the PK domain destabilized the dimer conformation of RNase L and allosterically inhibited its ribonuclease activity.