Nymannchristensen3991

AIMS Vimentin citrullination, the calcium (Ca2+ )-dependentpeptidylarginine deiminase (PAD)-mediated conversion of anarginine residue of vimentin to a citrulline residue,has emerged as a pathophysiological outcome ofautoimmune diseases and neurodegeneration. However, the roles, functions, and expression of citrullinated vimentinhave not yet been elucidated because available antibodies are limited. METHODS Wedevelopedmouse monoclonal IgG1 andIgMspecific for vimentin citrullinated at position R440 or R450 and applied Western blotting, immunohistochemistry, and immunofluorescent stainingtoinvestigate the pathogenesis of prion diseases in animal models,in patients with prion diseases, and in vitro. Sodium L-lactate RESULTS Vimentin was found to behighly citrullinated at R440 and R450,and these citrullinated formsweremainly expressed in reactive astrocytes in the brain tissues of scrapie-infected mice. Full-length and cleaved forms of citrullinated vimentin werefound in the cerebral corticesof sporadic Creutzfeldt-Jakob disease (sCJD) patients.The distribution of citrullinated vimentin was mainly confirmed in vimentin-, GFAP-, and YKL-40-positive reactive astrocytes. Biochemically, citrullination promoted resistance to the caspase-3- and caspase-9-mediated fragmentation of vimentin. Additionally,citrullination led to increased cytoplasmic and integral membrane/organellevimentin enrichment,whichindicated changes in theintrinsic solubility and distribution of vimentin. CONCLUSIONS Our observations suggestthat citrullinated vimentin acts as a specificindicatorfor the reactive state of astrocytes underabnormal neurological conditions. In addition, thesenovel antibodieswill be helpful for studying the role of citrullinated vimentin in the pathogenesis of human disorders. This article is protected by copyright. All rights reserved.AIM To compare the immunoexpression of RANK, MMP-9, and PTHrP in apical periodontitis lesions of diabetic and normoglycemic individuals. METHODOLOGY Primary chronic apical periodontitis lesions associated with teeth indicated for extraction in 13 type 2 diabetic individuals and 13 normoglycemic individuals who were screened for the glycemic index and glycated hemoglobin (HbA1c) were analysed. Individuals with other systemic diseases and users of anti-inflammatories and/or antibiotics in the previous 3 months, were excluded. Silanized slides with paraffin sections were used for immunohistochemical reactions and stained with haematoxylin and eosin for histopathological classification. The images were analyzed with an optical microscope and the slides were subdivided into 5 large fields assigning scores (0-2), according to the number of positive markings for each antibody. Fisher's exact test evaluated the parameters gender, type of lesion, location, and position in the arch. Non-parametric Mann-Whitney test waseen the groups. There was no significant correlation between the expression of bone resorption markers and the macroscopic size of the periapical lesions (p>0.05). CONCLUSIONS The bone resorption mediators analyzed had similar immunoexpression in the periapical lesions of diabetic and normoglycemic individuals. This article is protected by copyright. All rights reserved.The global COVID-19 pandemic has led to a worldwide shortage of ventilators. This shortage has initiated discussions of how to support multiple patients with a single ventilator (ventilator splitting). Ventilator splitting is incompletely tested, experimental and the effects have not been fully characterised. This study investigated the effect of ventilator splitting on system variables (inspiratory pressure, flow, and volume) and the possibility of different ventilation targets for each limb using only standard hospital equipment. Experiments were conducted on two test lungs with different compliances (0.02 and 0.04 l.cmH2 O-1 ). The ventilator was used in both pressure and volume control modes and was set to ventilate the low compliance lungs at end-tidal volumes of 500 ± 20 ml. A flow restrictor apparatus consisting of a Hoffman clamp and tracheal tube was connected in series to the inspiratory limb of the high compliance test lungs and the resistance modified to achieve end-tidal volumes of 500 ± 20 ml. The restriction apparatus successfully modified the inspiratory pressure, minute ventilation, and volume delivered to the high compliance test lungs in both pressure control (27.3-17.8 cm H2 O, 15.2-8.0 l.min-1 and 980-499 ml, respectively), and volume control (21.0-16.7 cm H2 O, 10.7-7.9 l.min-1 and 659-498 ml, respectively) ventilation modes. Ventilator splitting is not condoned by the authors. However, these experiments demonstrate the capacity to simultaneously ventilate two test lungs of different compliances, and using only standard hospital equipment, modify the delivered pressure, flow, and volume in each test lung. This article is protected by copyright. All rights reserved.Large sample theory of semi-parametric models based on maximum likelihood estimation (MLE) with shape constraint on the non-parametric component is well studied. Relatively less attention has been paid to the computational aspect of semi-parametric MLE. The computation of semi-parametric MLE based on existing approaches such as the EM algorithm can be computationally prohibitive when the missing rate is high. In this paper, we propose a computational framework for semi-parametric MLE based on an inexact block coordinate ascent algorithm. We show theoretically that the proposed algorithm converges. This computational framework can be applied to a wide range of data with different structures, such as panel count data, interval-censored data and degradation data, among others. Simulation studies demonstrate favorable performance compared with existing algorithms in terms of accuracy and speed. Two data sets are used to illustrate the proposed computational method. We further implement the proposed computational method in R package BCA1SG, available at CRAN. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND Ultraviolet radiation (UVR) is responsible for keratinocyte cancers (KC) through the induction of mutagenic cyclobutane pyrimidine dimers (CPDs). Many factors influence CPD repair in epidermal keratinocytes and a better understanding of those factors might lead to prevention strategies against skin cancer. OBJECTIVE The present study aims to evaluate the impact of dermal components on epidermal CPD repair efficiency and to investigate potential factors responsible for the dermal-epidermal crosstalk modulating UVR-induced DNA damage repair in keratinocytes. METHODS A model of self-assembled tissue-engineered skin containing human primary keratinocytes and fibroblasts has been used in this study. RESULTS We showed that CPD repair in keratinocytes is positively influenced by the presence of a dermis. We investigated the secretome and found that the cytokine CXCL5 is virtually absent in the culture medium of reconstructed skin, when compared to media from fibroblasts and keratinocytes alone. By modulating CXCL5 levels in culture media of keratinocytes, we have shown that CXCL5 is a CPD repair inhibitor.