Notes

Links between clinical and also histopathological characteristics in oral leukoplakia.
RESULTS Relaxin/RXFP1 signaling is important in both normal physiology and in human diseases. Reduced expression of RXFP1 in fibrotic lung and skin tissues surrenders both relaxin/RXFP1 signaling and their responsiveness to exogenous relaxin treatments. Alternative splicing and receptor dimerization are also important in regulating relaxin/RXFP1 signaling. CONCLUSIONS Understanding the molecular mechanisms that drive aberrant expression of RXFP1 in disease and the functional roles of alternative splicing and receptor dimerization will provide insight into therapeutic targets that may restore the relaxin responsiveness of fibrotic tissues. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.OBJECTIVE To describe the radiographic phenotype of axial spondyloarthritis (axSpA) according to the carriage of HLA-B27. METHODS An international collaboration compared the radiographic phenotype of axSpA according to HLA-B27 status. Patients with ankylosing spondylitis and axial psoriatic arthritis (PsA) were collected. Radiographs were read centrally, blinded to clinical details. The symmetry of the sacroiliac joints and lumbar syndesmophytes, the morphology of syndesmophytes (typical marginal vs atypical chunky) together with the modified Stoke Ankylosing spondylitis spinal score (mSASSS) and PsA spondylitis radiographic index (PASRI), were recorded. RESULTS 244 PsA patients and 198 AS patients were included. In PsA, 60 (25%) were HLA-B27 positive while in AS, 148 (75%) were HLA-B27 positive. Patients with HLA-B27 were younger, more often male and had a longer duration of disease. In multivariable logistic regression HLA-B27 was significantly associated with syndesmophyte symmetry (OR 3.02 (95% CI 1.38-6.61)) and marginal syndesmophytes (OR 1.97 (95% CI 1.16-3.36)) but not with sacroiliac symmetry. Mean radiographic scores were higher for patients with HLA-B27. CONCLUSIONS HLA-B27 positive axSpA patients have more severe radiographic damage, more marginal syndesmophytes, and more frequent syndesmophyte symmetry compared to HLA B27 negative patients. This article is protected by copyright. All rights reserved.We investigate activation of carbon dioxide by singly charged hydrated magnesium cations Mg .+ (H2 O)n , through infrared multiple photon dissociation (IRMPD) spectroscopy combined with quantum chemical calculations. The spectra of [MgCO2 (H2 O)n ].+ in the 1250-4000 cm-1 region show a sharp transition from n=2 to n=3 for the position of the CO2 antisymmetric stretching mode. This is evidence for the activation of CO2 via charge transfer from Mg .+ to CO2 for n≥3, while smaller clusters feature linear CO2 coordinated end-on to the metal center. Starting with n=5, we see a further conformational change, with CO2 .- coordination to Mg2+ gradually shifting from bidentate to monodentate, consistent with preferential hexa-coordination of Mg2+ . Our results reveal in detail how hydration promotes CO2 activation by charge transfer at metal centers. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.OBJECTIVE Evidence supports the validity of total knee arthroplasty (TKA) appropriateness classification based on the RAND Corporation and University of California Los Angeles system developed by Escobar and colleagues. The system, however, is approximately two decades old and the science and clinical application of TKA has changed dramatically. The purposes of our study was to 1) describe the methods used to develop a second-generation system, and 2) examine the structure of the system to determine the extent to which each of the indication criteria informed appropriateness. METHODS The development process is summarized. Multivariable multinomial regression analyses determined the extent to which each of eight individually analyzed indication criteria informed appropriateness judgements. Classification tree analysis illustrate how the indication criteria, in combination, led to judgements of Appropriate, Inappropriate or Uncertain. RESULTS An expert panel selected eight indication criteria (i.e., age, knee pain, function, radiographic osteoarthritis severity, osteoarthritis location, psychological factors, pain catastrophizing, and comorbidities). Piceatannol supplier A total of 1,008 clinical scenarios were written, based on the criteria. Regression analyses indicated that age, knee pain, function and radiographic severity dominated prediction of appropriateness while the other criteria played a smaller role. Classification tree analysis confirmed the regression findings. CONCLUSION Our second-generation classification system, which incorporates contemporary indicators of TKA prognosis and risk, demonstrated preliminary evidence for utility in clinical practice. This article is protected by copyright. All rights reserved.AIM For patients with severe haemophilia A, guidelines recommend prophylactic treatment with FVIII, with dose calculations targeting a predetermined FVIII trough level. However, this pharmacokinetic (PK) approach is suboptimal, with some patients experiencing breakthrough bleeds. We aimed to improve FVIII dosing by incorporating the thrombin generation assay, a global haemostasis assay whose main pharmacodynamic (PD) parameter, endogenous thrombin potential (ETP), predicts spontaneous bleeding risk. METHODS We performed post hoc combined PK-PD modelling using data from 66 adults who received human-cl rhFVIII (Nuwiq® , Octapharma AG) in a phase IIIb study. Time-to-event analyses simulated the probability of spontaneous bleeding for different FVIII exposures and baseline ETPs. RESULTS Ninety-one spontaneous bleeds occurred in 20/66 patients. The relationship between FVIIIC and ETP was non-linear, and the sigmoid Emax model adequately described the data. Individual PK-PD Bayesian estimation significantly improved predictive performance. Simulations showed that the mean spontaneous annual bleeding rate decreased with increasing baseline ETP or dosing with ETP values of 200, 400 and 600 (nmol/L)·min annual bleeding rates were 2.36, 1.25 and 0.66, respectively, on 40 IU/kg human-cl rhFVIII every 3 days; and annual bleeding rates were 2.09, 1.10, and 0.60, respectively, on 60 IU/kg every 3 days. CONCLUSION Prophylactic FVIII dosing is more clinically meaningful when incorporating ETP alongside FVIII level. For the first time, FVIII dosing can be personalized with the aim of eliminating spontaneous breakthrough bleeds. © 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.
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