Evaluating the safety and short-term equivalence of colchicine versus prednisone in older patients with acute calcium pyrophosphate crystal arthritis (COLCHICORT): an open-label, multicentre, randomised trial.

Background: Acute calcium pyrophosphate crystal arthritis causes intense joint pain mainly affecting older people. Because guidance and evidence remain scarce, management of this disease relies on expert opinion. We therefore aimed to compare the safety and short-term equivalence of low-dose colchicine with oral prednisone in older patients with acute calcium pyrophosphate crystal arthritis.

A Qualitative Analysis of the Optimal Discharge Summary: Effective Communication of Medication Changes for Older Patients.

The importance of the discharge summary (DS) is well recognized. The format to be used is also important, but this aspect has not yet been studied in the literature. The purpose of this work was to establish a DS format for older patients that ensures effective communication with general practitioners (GPs).

Oxidant resistant human apolipoprotein A-I functions similarly to the unmodified human isoform in delaying atherosclerosis progression and promoting atherosclerosis regression in hyperlipidemic mice.

Background: Transgenic overexpression of apolipoprotein A-I (apoA1) has been shown to delay atherosclerosis lesion progression and promote lesion regression in mouse models; however, apoA1 is subject to oxidation by myeloperoxidase (MPO) and loss of function. The activity of oxidant resistant human apoA1 was compared to unmodified human apoA1 in mouse models of atherosclerosis progression and regression.

Methods And Results: Human apoA1 and the MPO oxidant resistant 4WF isoform transgenic mice were bred to LDL receptor deficient (LDLr KO) mice and fed a western-type diet.

Quantitative trait locus mapping identifies the Gpnmb gene as a modifier of mouse macrophage lysosome function.

We have previously shown that the DBA/2J versus AKR/J mouse strain is associated with decreased autophagy-mediated lysosomal hydrolysis of cholesterol esters. Our objective was to determine differences in lysosome function in AKR/J and DBA/2J macrophages, and identify the responsible genes. Using a novel dual-labeled indicator of lysosome function, DBA/2J versus AKR/J bone marrow derived macrophages had significantly decreased lysosome function.

Corrigendum: Blockade of IL-33R/ST2 Signaling Attenuates Ileitis Depending on IL-22 Expression.

[This corrects the article DOI: 10.3389/fimmu.2019.

Soat1 mediates the mouse strain effects on cholesterol loading-induced endoplasmic reticulum stress and CHOP expression in macrophages.

We previously demonstrated that AKR vs. DBA/2 mouse bone marrow derived macrophages have higher levels of free cholesterol and lower levels of esterified cholesterol after cholesterol loading, and that AKR, but not DBA/2, macrophages induced C/EBP homologous protein (CHOP) expression after cholesterol loading. We earlier determined that the free and esterified cholesterol level effect is due to a truncation in the sterol O-acyltransferase 1 (Soat1) gene, encoding acetyl-coenzyme A acetyltransferase 1 (ACAT1).

Confirmation of Ath26 locus on chromosome 17 and identification of Cyp4f13 as an atherosclerosis modifying gene.

Background And Aims: We previously demonstrated that Apoe mice on DBA/2 vs. AKR genetic background have >10-fold larger atherosclerotic lesions. Prior quantitative trait locus mapping via strain intercrossing identified a region on chromosome 17, Ath26, as the strongest atherosclerosis-modifying locus.

Blockade of IL-33R/ST2 Signaling Attenuates Ileitis Depending on IL-22 Expression.

Oral infection (30 cysts of 76K strain) induces acute lethal ileitis in sensitive C57BL/6 (B6) mice with increased expression of IL-33 and its receptor ST2 in the ileum. Here we show that IL-33 is involved in ileitis, since absence of IL-33R/ST2 attenuated neutrophilic inflammation and Th1 cytokines upon infection with enhanced survival. Blockade of ST2 by neutralizing ST2 antibody in B6 mice conferred partial protection, while rmIL-33 aggravated ileitis.

Microscopic imaging as a tool to target spatial and temporal extraction of bioactive compounds through ultrasound intensification.

Unravelling a chain of events in ultrasound-assisted extraction (UAE) of bioactive compounds from plants has to start with a detailed description of destructuration at macroscopic and microscopic scale. The present work aims to study the impacts and interactions of UAE on the extreme complexity and diversity of plants structures. Three plant species were selected for their difference in specialized structures and their spatial distribution of secondary metabolites: bitter orange leaf (C.

Correction: Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

The original version of this Article omitted the author Dr Mathias Chamaillard from the l'Institut de Pasteur, Lille, France. This has been corrected in both the PDF and HTML versions of the Article.

Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation.

Histo-cytochemistry and scanning electron microscopy for studying spatial and temporal extraction of metabolites induced by ultrasound. Towards chain detexturation mechanism.

There are more than 1300 articles in scientific literature dealing with positive impacts of Ultrasound-Assisted Extraction (UAE) such as reduction of extraction time, diminution of solvent and energy used, enhancement in yield and even selectivity, intensification of diffusion, and eliminating wastes. This present study aims to understand what are the mechanism(s) behind these positive impacts which will help to design a decision tool for UAE of natural products. Different microscopic observations (Scanning Electron Microscopy (SEM), Environmental Scanning Electron Microscopy (e-SEM), Cyto-histochemistry) have been used for spacial and temporal localization of metabolites in rosemary leaves, which is one of the most studied and most important plant for its antioxidant metabolites used in food industry, during conventional and ultrasound extraction.

Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies-Statement From ATVB Council.

There are many differences in arterial diseases between men and women, including prevalence, clinical manifestations, treatments, and prognosis. The new policy of the National Institutes of Health, which requires the inclusion of sex as a biological variable for preclinical studies, aims to foster new mechanistic insights and to enhance our understanding of sex differences in human diseases. The purpose of this statement is to suggest guidelines for designing and reporting sex as a biological variable in animal models of atherosclerosis, thoracic and abdominal aortic aneurysms, and peripheral arterial disease.

Quantitative Trait Locus Mapping of Macrophage Cholesterol Metabolism and CRISPR/Cas9 Editing Implicate an ACAT1 Truncation as a Causal Modifier Variant.

Objective: Cholesterol metabolism is a dynamic process involving intracellular trafficking, cholesterol esterification, and cholesterol ester hydrolysis. Our objective was to identify genes that regulate macrophage cholesterol metabolism.

Approaches And Results: We performed quantitative trait loci mapping of free and esterified cholesterol levels and the ratio of esterified to free cholesterol in acetylated low-density lipoprotein-loaded bone marrow-derived macrophages from an AKR×DBA/2 strain intercross.

First Report of CD4 Lymphopenia and Defective Neutrophil Functions in a Patient with Amebiasis Associated with CMV Reactivation and Severe Bacterial and Fungal Infections.

We report the case of a patient with acute necrotizing colitis due to invasive amebiasis associated with CD4 lymphopenia and impaired neutrophil responses. The course of the disease was characterized by CMV reactivation and severe and recurrent bacterial and fungal infections, which might be related to the decreased CD4 T cell count and the impaired functional capacities of neutrophils, respectively. The clinical outcome was positive with normalization of both CD4 cell count and neutrophil functions.

Free-cholesterol-mediated autophagy of ORMDL1 stimulates sphingomyelin biosynthesis.

Cholesterol confers unique biophysical properties to the plasma membrane bilayer that are essential for maintaining optimal membrane fluidity, which in turn regulate multiple physiological functions required to promote cellular integrity and viability. Conversely, excessive cholesterol causes pathological conditions such as atherosclerosis that can lead to heart attacks. Human atheroma macrophages carry a large burden of free cholesterol (FC) in addition to cholesterol esters.

ORMDL orosomucoid-like proteins are degraded by free-cholesterol-loading-induced autophagy.

Eukaryotic cells have evolved robust mechanisms to counter excess cholesterol including redistribution of lipids into different compartments and compensatory up-regulation of phospholipid biosynthesis. We demonstrate here that excess cellular cholesterol increased the activity of the endoplasmic reticulum (ER) enzyme serine palmitoyl-CoA transferase (SPT), the rate-limiting enzyme in sphingomyelin synthesis. This increased SPT activity was not due to altered levels of SPTLC1 or SPTLC2, the major subunits of SPT.

[French geriatric day hospitals managing falls].

Introduction: Falling is a serious hazard for the elderly that may lead to severe injury, loss of independence, and death. The aim of the study was to describe the resources devoted by French geriatric day hospitals for the assessment and care of elderly fallers, by differentiating medicine day hospitals and rehabilitation day hospitals.

Method: Department heads listed in the directory of the Association for the Promotion of the Day Hospitals for Elderly people (APHJPA) were contacted by email and invited to answer a questionnaire online.

A polysaccharide virulence factor of a human fungal pathogen induces neutrophil apoptosis via NK cells.

Aspergillus fumigatus is an opportunistic human fungal pathogen that sheds galactosaminogalactan (GG) into the environment. Polymorphonuclear neutrophils (PMNs) and NK cells are both part of the first line of defense against pathogens. We recently reported that GG induces PMN apoptosis.

The protein phosphatase PhzA of A. fumigatus is involved in oxidative stress tolerance and fungal virulence.

Protein phosphatases Z that are unique to the fungal kingdom have been associated to resistance to high salt concentration, cell wall integrity, cell cycle regulation, and oxidative stress in fungi. In Aspergillus fumigatus, it was shown that PHZA is under the control of the transcription factor Skn7 and is only involved in the control of the oxidative stress. Accordingly, the ΔphzA mutant showed a defect in virulence in an experimental model of corneal infection in immunocompetent animals and that the impact on susceptibility to cell wall drugs is only secondary.

A₁ adenosine receptor deficiency or inhibition reduces atherosclerotic lesions in apolipoprotein E deficient mice.

Aims: The goal of this study was to determine whether the A1 adenosine receptor (AR) plays a role in atherosclerosis development and to explore its potential mechanisms.

Methods And Results: Double knockout (DKO) mice, deficient in the genes encoding A1 AR and apolipoprotein E (apoE), demonstrated reduced atherosclerotic lesions in aortic arch (en face), aortic root, and innominate arteries when compared with apoE-deficient mice (APOE-KO) of the same age. Treating APOE-KO with an A1 AR antagonist (DPCPX) also led to a concentration-dependent reduction in lesions.

Ribosomal protein L13a deficiency in macrophages promotes atherosclerosis by limiting translation control-dependent retardation of inflammation.

Objective: Unresolved inflammatory response of macrophages plays a pivotal role in the pathogenesis of atherosclerosis. Previously we showed that ribosomal protein L13a-dependent translational silencing suppresses the synthesis of a cohort of inflammatory proteins in monocytes and macrophages. We also found that genetic abrogation of L13a expression in macrophages significantly compromised the resolution of inflammation in a mouse model of lipopolysaccharide-induced endotoxemia.

Blockade of IL-1R signaling diminishes Paneth cell depletion and Toxoplasma gondii induced ileitis in mice.

Interleukin 1 is a critical inflammatory mediator and involved in host defense to several pathogens. Oral T. gondii infection causes lethal ileitis in C57BL/6 (BL6) mice and serves to investigate the mechanisms of acute intestinal inflammation.

Opposing Mcl-1, the GALIG proapoptotic gene is upregulated as neutrophils die and underexpressed in Acute Myeloid Leukemia cells.

GALIG gene expression induces apoptosis in cultured cells through a pathway still under investigation. It is highly expressed in leukocytes but weakly detectable in bone marrow, suggesting a role in the myeloid lineage homeostasis. We show here that GALIG-induced cell death is counteracted by the overexpression of MCL-1, a pro-survival member of the Bcl2 family.