072). The most common adverse events for fenebrutinib included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. CONCLUSION Fenebrutinib demonstrated efficacy comparable to adalimumab in patients with an inadequate response to methotrexate, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA. This article is protected by copyright. All rights reserved.For the past seven years, the European and the North-American experience with biosimilars have diverged. While the implementation and clinical experience with biosimilars have developed rapidly in many European countries, the United States has stalled. In a paper published in this issue of Arthritis and Rheumatology, Baker and colleagues discuss how this disparity came about and also how it may be corrected (1). This article is protected by copyright. All rights reserved.OBJECTIVE The aim of this study is to compare tissue sodium and fat content in the upper and lower extremities of participants with lipedema versus controls using magnetic resonance imaging (MRI). METHODS MRI was performed at 3.0 T in females with lipedema (n = 15, age = 43.2 ± 10.0 years, BMI = 30.3 ± 4.4 kg/m2 ) and controls without lipedema (n = 14, age = 42.8 ± 13.2 years, BMI = 28.8 ± 4.4 kg/m2 ). Participants were assessed for pain and disease stage. Sodium MRI was performed in the forearm and calf to quantify regional tissue sodium content (TSC, mmol/L). Chemical-shift-encoded water-fat MRI was performed in identical regions for measurement of fat/water (ratio). RESULTS In the calf, skin TSC (16.3 ± 2.6 vs. 14.4 ± 2.2 mmol/L, P = 0.04), muscle TSC (20.3 ± 3.0 vs. 18.3 ± 1.7 mmol/L, P = 0.03), and fat/water (1.03 ± 0.37 vs. 0.56 ± 0.21 ratio, P  less then  0.001) were significantly higher in participants with lipedema versus control participants. In the forearm, skin TSC (13.4 ± 3.3 vs. 12.0 ± 2.3 mmol/L, P = 0.2, Cohen's d = 0.50) and fat/water (0.65 ± 0.24 vs. 0.48 ± 0.24 ratio, P = 0.07, Cohen's d = 0.68) demonstrated moderate effect sizes in participants with lipedema versus control participants. Calf skin TSC was significantly correlated with pain (Spearman's rho = 0.55, P = 0.03) and disease stage (Spearman's rho = 0.82, P  less then  0.001) among participants with lipedema. CONCLUSIONS MRI-measured tissue sodium and fat content are significantly higher in the lower extremities, but not upper extremities, of patients with lipedema compared with BMI-matched controls. © 2020 The Obesity Society.In a matter of weeks, the COVID19 crisis has totally upended clinical medicine and the practice of rheumatology. Our old ways of seeing patients in person, precepting fellows in clinic or on the consult service, and leading in-person interactive teaching rounds are gone for now and possibly for good. But how can we replace these critical teaching and training elements? Despite the mounting challenges of managing an exploding population of coronavirus infected patients and caregivers, we must find innovative ways to foster our trainees' professional development. This article is protected by copyright. All rights reserved.Demyelination is a common pathological feature of a large number of neurodegenerative diseases including multiple sclerosis and Huntington's disease (HD). Laquinimod (LAQ) has been found to have therapeutic effects on multiple sclerosis and HD. However, the mechanism underlying LAQ's therapeutic effects remains unknown. Using HD mice that selectively express mutant huntingtin in oligodendrocytes and show demyelination, we found that LAQ reduces the Ser259 phosphorylation on myelin regulatory factor (MYRF), an oligodendrocyte-specific transcription factor promoting the expression of myelin-associated genes. The reduced MYRF phosphorylation inhibits MYRF's binding to mutant huntingtin and increases the expression of myelin-associated genes. We also found that PRKG2, a cGMP-activated protein kinase subunit II, promotes the Ser259-MYRF phosphorylation and that knocking down PRKG2 increased myelin-associated protein's expression in HD mice. Our findings suggest that PRKG2-regulated phosphorylation of MYRF is involved in demyelination and can serve as a potential therapeutic target for reducing demyelination. © 2020 The Authors."Young people should study chemistry because it is a cross between playing with lego and cooking. The secret of being a successful scientist is to look for answers beyond the flask in your hands …" Find out more about Jack K. Clegg in his Author Profile. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.OBJECTIVE This in vitro study aims to evaluate load-to-failure of ceramic veneers with butt joint (BJ) and feathered edge (FE) incisal preparation designs, and to correlate these results to the failure mode of the restorations. MATERIALS AND METHODS One hundred and forty-eight typodont teeth (customized Nissin A25A-UL19B) were divided into two different preparation configurations BJ and FE and two different loading angulations, 0° and 20°. Lithium disilicate ceramic veneers (IPS e.max CAD, Ivoclar Vivadent) were milled using computer-aided-design-and-computer-aided-manufacturing (CAD/CAM) techniques. Veneers were bonded to typodont teeth with resin cement (IPS Variolink Esthetic, Ivoclar Vivadent). Each group was loaded at the incisal edge using an Instron Universal Testing Machine at a crosshead speed of 0.01 mm/s till failure. RESULTS Pairwise comparison showed veneers from the BJ groups had a significantly higher load-to-failure value compared to the FE groups. Veneers with a FE preparation design loaded at 20° angulation had the lowest load-to-failure value.  https://www.selleckchem.com/products/oprozomib-onx-0912.html  CONCLUSIONS Within the limitations of the present study, both incisal preparation designs and loading angulations have significant effects on the load-to-failure values of ceramic veneers. BJ group exhibits a significantly higher load-to-failure value compared to the FE group. CLINICAL SIGNIFICANCE BJ incisal preparation is preferred over FE preparation design. © 2020 Wiley Periodicals, Inc.