MW01-6-189WH (MW189) is a novel central nervous system-penetrant small-molecule drug candidate that selectively attenuates stressor-induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first-in-human, randomized, double-blind, placebo-controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug-related treatment-emergent adverse event was infusion-site reactions, likely related to drug solution acidity. No clinically concerning changes were seen in vital signs, electrocardiograms, physical or neurological examinations, or safety laboratory results. PK analysis showed dose-proportional increases in plasma concentrations of MW189 after single or multiple doses, with approximately linear kinetics and no significant drug accumulation. Steady state was achieved by dose 3 for all dosing cohorts. A pilot pharmacodynamic study administering low-dose endotoxin to induce a systemic inflammatory response was done to evaluate the effects of a single intravenous dose of MW189 on plasma cytokine levels. MW189 treatment resulted in lower levels of the proinflammatory cytokine TNF-α and higher levels of the anti-inflammatory cytokine IL-10 compared with placebo treatment. The outcomes are consistent with the pharmacological mechanism of MW189. Overall, the safety profile, PK properties, and pharmacodynamic effect support further development of MW189 for patients with acute brain injury. © 2020 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.Transplant ureteric stent insertion reduces the incidence of MUCs, but it is not known whether routine PSRGU is needed to detect unmasked MUCs. This study evaluated whether routine PSRGU in the pRTR is a useful tool to identify MUCs before they become clinically apparent. A retrospective analysis was undertaken of the clinical outcomes following elective stent removal from pediatric kidney-only transplant recipients at two London centers between 2012 and 2016. Our policy was to perform PSRGU either routinely or urgently if there were concerning symptoms or biochemical evidence of renal allograft dysfunction. Elective stent removal was performed in 86% (97 of 113 pRTR), and 75 (77%) of whom had routine PSRGU at a median (IQR) of 6 (2-8) days after stent removal. There were changes to management in 3 (4%) of pRTR with PSRGU identifying no MUC. Nineteen patients (25%) had urgent PSRGU, most commonly due to renal allograft dysfunction, at a median (IQR) of 5.5 (2.7-12.3) days after stent removal. Of these, two pRTR required ureteric intervention. For our current practice of removing transplant stents at 4-6 weeks post-transplantation, our study has found no evidence to support routine PSRGU after elective stent removal. selleck chemicals llc © 2020 Wiley Periodicals, Inc.IMPORTANCE Long-term data on age-related cataract, a leading cause of blindness and visual impairment, is scarce in Asian populations. BACKGROUND We report the 6-year incidence and progression of age-related cataract and associated risk factors in Malay adults living in Singapore. DESIGN Population-based cohort study PARTICIPANTS 3280 Malays aged 40+ years participated in baseline examinations of the Singapore Malay Eye Study (2004-2006). Six years later, 1901 (72.1% of eligible) baseline participants were re-examined. METHODS Cataract was assessed using lens photos, taken during eye examinations, following the Wisconsin Cataract Grading System. MAIN OUTCOMES AND MEASURES Incidence and progression of cortical, nuclear and posterior subcapsular (PSC) cataract. Poisson regression models and generalised estimating equations models (with Poisson link) were used to assess factors associated with cataract incidence and progression, respectively, adjusting for age, sex and other risk factors. RESULTS Age-adjusted 6-year incidence of cortical, nuclear and posterior subcapsular (PSC) cataract was 14.1%, 13.6% and 8.7%, respectively, and was strongly age-related (P for trend less then 0.001 for all types). Diabetes (relative risk [RR], 1.97; 95% confidence intervals [CI], 1.46-2.67) was associated with incident cortical cataract, hypertension was associated with PSC cataract incidence (RR, 2.09; 95% CI, 1.22-3.61), after multivariable adjustment. Progression occurred in 20.4%, 5.9% and 40.6% of baseline cortical, nuclear and PSC cataract cases, respectively. CONCLUSIONS AND RELEVANCE Similar to other elderly populations, incidence and progression of cataract was common in this Malay population. Diabetes and hypertension were important modifiable risk factors for cataract, highlighting the importance of systemic health on eye disease. This article is protected by copyright. All rights reserved.Various polyimides and polyamides have recently been prepared via hydrothermal synthesis in nothing but H 2 O under high-pressure and high-temperature conditions. However, none of the prepared polymers feature a truly conjugated polymer backbone. Herewith, we report an expansion of the synthetic scope of this straightforward and inherently environmentally friendly polymerization technique to the generation of conjugated polymers. Selected representatives of two different polymer classes, pyrrone polymers and polybenzimidazoles, were generated hydrothermally. In addition to a mechanistic discussion of the polymer formation also an electrochemical characterization of the most promising product is presented. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Malignant tumor endangers seriously the health of all mankind. Multidrug resistance (MDR) is one of the main causes of clinical tumor chemotherapy failure. Curcumin (CUR) has not only antitumor activity but also reversing tumor MDR effect. CUR reverses tumor MDR via regulating related signal pathways or corresponding expressed proteins or gene. When combined with chemotherapeutic agents, CUR can be a chemotherapeutic sensitive agent to enhance chemotherapy efficacy and weaken tumor MDR. On the other hand, to improve the MDR reversal effect of CUR, its derivatives have been extensively studied. Therefore, this article mainly focuses on reviewing the application of CUR and its derivatives in MDR and its mechanism of reversing MDR. © 2020 John Wiley & Sons, Ltd.