Mogensenlund3781

KGaA, Weinheim.BACKGROUND Threatened miscarriage is a common complication of pregnancy. Results of randomized controlled trials on the efficacy of progestogen in the treatment of threatened miscarriage remain inconsistent. OBJECTIVE To investigate whether the use of progestogen is associated with improved event rate of live birth and other benefits in women with threatened miscarriage SEARCH STRATEGY Ovid Medline, Ovid Embase, and Cochrane CENTRAL Register of Controlled Trials from their inception until July 8, 2019. SELECTION CRITERIA Randomized controlled trials comparing progestogen with a placebo or no treatment for pregnancy outcomes in women with threatened miscarriage. DATA COLLECTION AND ANALYSIS Two authors independently conducted data extraction and assessed study quality. We calculated risk ratios (RR) and 95% confidence intervals using the Mantel-Haenszel approach for dichotomous outcomes. MAIN RESULTS Ten trials totaling 5056 participants were eligible for analysis. The use of progesterone increased the incidence of live birth (RR 1.07, 95% CI 1.00 to 1.15; P=0.04; I2 =18%), with benefit only seen in use of oral progestogen (RR 1.17, 95% CI 1.04 to 1.31; P=0.008; I2 =0%) and not in vaginal progesterone (RR 1.04, 95% CI 1.00 to 1.08; P=0.07; I2 =0%;). Similarly, progestogen reduced the risk of miscarriage (RR 0.73, 95% CI 0.59 to 0.92), with benefit only seen in oral progestogen and not in vaginal progesterone. CONCLUSION Progestogens may have benefits on live birth rate and miscarriage rate for women with threatened miscarriage. These benefits appear to be confined to the use of oral progestogen, and no statistically significant improvements were seen with vaginal progesterone. This article is protected by copyright. All rights reserved.The health crisis caused by the novel SARS-cov-2 (formally called 2019-nCoV) related pandemic requires urgent action, including a necessary therapeutic response. Pregnant women are just as exposed as the general population and should not be excluded, because of their status, from discussions on effective and well tolerated candidate treatments. This article is protected by copyright. All rights reserved.BACKGROUND Soluble-type hemojuvelin in serum and urine has been shown to be a biomarker in humans for chronic kidney disease (CKD) and acute kidney injury (AKI). No similar research has been conducted on cats. OBJECTIVE Urine hemojuvelin (u-hemojuvelin) can be used as a clinical indicator for cats with various renal diseases. ANIMALS Eighteen healthy cats, 10 cats with AKI, 21 cats with acute-on-chronic kidney injury (ACKI), and 45 cats with CKD were enrolled. METHODS The expression profile of u-hemojuvelin was assessed by Western blot analysis, whereas the u-hemojuvelin concentration was measured using an in-house sandwich ELISA. Each cat's u-hemojuvelin-to-creatinine ratio (UHCR) also was determined. RESULTS Significant differences were found in both u-hemojuvelin concentration and UHCR between the control cats and the other cats (AKI, CKD, ACKI). Both u-hemojuvelin and UHCR had high areas under the receiver operator curve (AUROC) for diagnoses of AKI (u-hemojuvelin, 0.885; UHCR, 0.982), CKD (hemojuvelin, 0.869; UHCR, 0.959), and ACKI (hemojuvelin, 0.910; UHCR, 1). Late stage (International Renal Interest Society, IRIS stages 3 and 4) CKD cats had significantly higher u-hemojuvelin concentration and UHCR than did early stage cats (IRIS stages 1 and 2). Both u-hemojuvelin and UHCR were significantly correlated with high blood urea nitrogen, plasma creatinine, and plasma phosphate concentrations and with low hematocrit (Hct), red blood cell (RBC) count, and plasma albumin concentration. The UHCR values were also significantly correlated with white blood cell count in blood. CONCLUSION Both u-hemojuvelin and UHCR potentially can serve as diagnostic indicators for a range of renal diseases in cats. © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.The coronavirus SARS-CoV-2 (i.e., COVID-19) has caused significant disruption in everyday life on a global scale. Due to stay-at-home orders and sudden unemployment, millions have found themselves isolated at home without their usual routines. This rise in unstructured time, combined with the enormous stress of the pandemic and its far-reaching consequences, have led to widespread concerns among the general public about vulnerability to overeating, sedentary behavior, and weight gain. These concerns are reflected in the explosion of social media posts referencing the "quarantine-15." This article is protected by copyright. All rights reserved.Hereditary transthyretin amyloidosis (ATTR) is a disease characterized by the extracellular deposition of transthyretin (TTR) amyloid fibrils. Highly destabilizing TTR mutations cause leptomeningeal amyloidosis, a rare, but fatal, disorder in which TTR aggregates in the brain. The disease remains intractable, since liver transplantation, the reference therapy for systemic ATTR, does not stop mutant TTR production in the brain. In addition, despite current pharmacological strategies have shown to be effective against in vivo TTR aggregation by stabilizing the tetramer native structure and precluding its dissociation, they display low brain permeability. Recently, we have repurposed tolcapone as a molecule to treat systemic ATTR. Crystal structures and biophysical analysis converge to demonstrate that tolcapone binds with high affinity and specificity to three unstable leptomeningeal TTR variants, stabilizing them and, consequently, inhibiting their aggregation. Because tolcapone is an FDA-approved drug that crosses the blood-brain barrier, our results suggest that it can translate into a first disease-modifying therapy for leptomeningeal amyloidosis. DATABASES PDB codes for A25T-TTR, V30G-TTR, and Y114C-TTR bound to tolcapone are 6TXV, 6TXW, and 6XTK, respectively. Fetuin © 2020 Federation of European Biochemical Societies.The COVID-19 pandemic caused by SARS-CoV-2 infection is spreading at an alarming rate and has created an unprecedented health emergency around the globe. There is no effective vaccine or approved drug treatment against COVID-19 and other pathogenic coronaviruses. The development of antiviral agents is an urgent priority. Biochemical events critical to the coronavirus replication cycle provided a number of attractive targets for drug development. These include, spike protein for binding to host cell-surface receptors, proteolytic enzymes that are essential for processing polyproteins into mature viruses, and RNA-dependent RNA polymerase for RNA replication. There has been a lot of ground work for drug discovery and development against these targets. Also, high-throughput screening efforts have led to the identification of diverse lead structures, including natural product-derived molecules. This review highlights past and present drug discovery and medicinal-chemistry approaches against SARS-CoV, MERS-CoV and COVID-19 targets.