Greer Abernathy (papertrail2)

Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.BACKGROUND AND OBJECTIVES The role of serotonin-norepinephrine reuptake inhibitors (SNRIs) in migraine prophylaxis has not been completely established. Current treatments for vestibular migraine (VM) are based on scarce evidence. We aimed to perform an updated review focusing on the efficacy and tolerability of SNRIs for migraine and VM prevention. METHODS We searched the PubMed, Web of Science, and Cochrane Library databases for relevant studies. The primary outcome was migraine frequency. In the case of VM, the Dizziness Handicap Inventory (DHI) scores and Vertigo Severity Scores (VSSs) were extracted. RESULTS Six randomized controlled trials involving 418 patients were analyzed. Patients receiving SNRIs had fewer migraine days than those receiving a placebo (standardized mean difference -0.38, 95% CI -0.76 to -0.01, p=0.04). The effects of SNRIs and other active drugs were comparable. In patients with VM, venlafaxine had a significant advantage over other active drugs in decreasing the VSS (weighted mean difference (MD) -1.45, 95% CI -2.11 to -0.78, p less then 0.0001) and the emotional domain score of the DHI (MD -2.64, 95% CI -4.97 to -0.31, p=0.03). We found no significant difference in the rate of withdrawals due to any reason or withdrawals due to side effects between SNRIs and active drugs and between SNRIs and a placebo. CONCLUSIONS SNRIs were clinically safe and effective for migraine and VM prophylaxis, were better than a placebo, and not inferior to other active drugs. SNRIs may be a preferable choice for patients with VM with psychiatric disorders. © American Society of Regional Anesthesia & Pain Medicine 2020. No commercial re-use. See rights and permissions. Published by BMJ.Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing the pathway components in ordered microdomains on the cell surface. Cellular responses regulated by lipid rafts range from physiological to pathological, and the success of a therapeutic approach targeting "pathological" lipid rafts depends on the ability of a remedial agent to recognize them and disrupt pathological lipid rafts without affecting normal raft-dependent cellular functions. In this article, concluding the Thematic Review Series on Biology of Lipid Rafts, we review current experimental therapies targeting pathological lipid rafts, including examples of inflammarafts (iRafts) and cluster of apoptotic signaling molecule-enriched rafts (CASMERs). The corrective approaches include regulation of cholesterol and sphingolipid metabolism and membrane trafficking by using HDL and its mimetics, liver X receptor (LXR) agonists, ABCA1 overexpression, and cyclodextrins, as well as a more targeted intervention with apolipoprotein A-I binding protein (AIBP). Among others, we highlight the design of antagonists that target inflammatory receptors only in their activated form of homo- or heterodimers, when receptor dimerization occurs in pathological lipid rafts. Other therapies aim to promote raft-dependent physiological functions, such as augmenting caveolae-dependent tissue repair. The overview of this highly dynamic field will provide readers with a view on the emerging concept of targeting lipid rafts as a therapeutic strategy. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.BACKGROUND The secretion of organic solutes by the proximal tubules is an essential intrinsic kidney function. However, the clinical significance of the kidney's clearance of tubular secretory solutes is uncertain. METHODS In this prospective cohort study, we evaluated 3416 participants with CKD from the Chronic Renal Insufficiency Cohort (CRIC) study. We measured plasma and 24-hour urine concentrations of endogenous candidate secretory solutes at baseline, using targeted liquid chromatography-tandem mass spectrometry. The study defined CKD progression by