Role of Self-Stigma in Pathways from HIV-Related Stigma to Quality of Life among People Living with HIV

Funding Information: This study was supported by Viiv Healthcare, Gilead, and Aidsfonds (research Grant Number AF-P.42601). The funders had no role in decisions regarding the study design, data analysis, or publication. Acknowledgments We extend our gratitude to all PLHIV who completed the survey. We further thank the HIV specialist nurses and doctors at OLVG hospital for their effort in recruiting patients to complete the surveys.Peer reviewedPublisher PD

TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions

Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease

Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia

Glucocorticoids (GCs) and topoisomerase II inhibitors are used to treat acute lymphoblastic leukaemia (ALL) as they induce death in lymphoid cells through the glucocorticoid receptor (GR) and p53 respectively. Mechanisms underlying ALL cell death and the contribution of the bone marrow microenvironment to drug response/resistance remain unclear. The role of the microenvironment and the identification of chemoresistance determinants were studied by transcriptomic analysis in ALL cells treated with Dexamethasone (Dex), and Etoposide (Etop) grown in the presence or absence of bone marrow conditioned media (CM). The necroptotic (RIPK1) and the apoptotic (caspase-8/3) markers were downregulated by CM, whereas the inhibitory effects of chemotherapy on the autophagy marker Beclin-1 (BECN1) were reduced suggesting CM exerts cytoprotective effects. GCs upregulated the RIPK1 ubiquitinating factor BIRC3 (cIAP2), in GC-sensitive (CEM-C7-14) but not in resistant (CEM-C1-15) cells. In addition, CM selectively affected GR phosphorylation in a site and cell-specific manner. GR is recruited to RIPK1, BECN1 and BIRC3 promoters in the sensitive but not in the resistant cells with phosphorylated GR forms being generally less recruited in the presence of hormone. FACS analysis and caspase-8 assays demonstrated that CM promoted a pro-survival trend. High molecular weight proteins reacting with the RIPK1 antibody were modified upon incubation with the BIRC3 inhibitor AT406 in CEM-C7-14 cells suggesting that they represent ubiquitinated forms of RIPK1. Our data suggest that there is a correlation between microenvironment-induced ALL proliferation and altered response to chemotherapy

The health- and addictive effectes due to exposure to aldehydes of cigarette smoke. Part 1; Acetaldehyde, Formaldehyde, Acrolein and Propionaldehyde

In deze literatuurstudie worden de gezondheids- en mogelijke verslavende effecten van blootstelling aan aldehyden ten gevolge van het roken van sigaretten beschreven. Dit literatuuronderzoek richt zich met name op acetaldehyde, formaldehyde, acrolein, en propionaldehyde. Alle aldehyden veroorzaken pathologische schade aan de luchtwegen en bereiken hoge piekconcentraties in de luchtwegen tijdens het roken. In ratten leidt een gecombineerde blootstelling aan de genoemde aldehyden tot een significante toename van de schade aan de luchtwegen en tot een afname van de ademfrequentie. Bij lage concentraties wordt als gevolg van combineren geen potentiering van de schade gezien. Onduidelijk is of tijdens het roken van sigaretten, waarbij hoge piek concentraties ontstaan, potentiering van de schade optreedt. Alhoewel er vanuit dierexperimenteel onderzoek aanwijzingen zijn dat met name acetaldehyde verslavende eigenschappen heeft, is in de geraadpleegde literatuur geen onderbouwing gevonden voor verslaving aan ge6nhaleerde aldehyden.<br

The effect of the interleukin-1 cytokine family members IL-1F6 and IL-1F8 on adipocyte differentiation.

Contains fulltext : 88907.pdf (publisher's version ) (Closed access)Obesity is characterized by chronic low-grade inflammation originating from expanding adipose tissue. In the present study, we examined the adipogenic expression levels of IL-1F6 and IL-1F8, both members of the IL-1 family of cytokines, and their effects on adipose tissue gene expression. Although IL-1F6 is primarily present in adipose tissue resident macrophages and induced by inflammation, IL-1F8 is absent. IL-1F6, but not IL-1F8, reduces adipocyte differentiation, as shown by a significant decrease in PPARgamma gene expression. Finally, both IL-1F6 and IL-1F8 are able to induce inflammatory gene expression in mature adipocytes. In conclusion, we demonstrate for the first time that IL-1F6 is present in adipose tissue and that IL-1F6 and IL-1F8 are involved in the regulation of adipose tissue gene expression. Importantly, IL-1F6 inhibits PPARgamma expression which may lead to reduced adipocyte differentiation suggesting metabolic effects of this cytokine.1 november 201

Long-term taurine supplementation leads to enhanced hepatic steatosis, renal dysfunction and hyperglycemia in mice fed on a high-fat diet

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO803339351FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãosem informaçã