Rice bran derivatives alleviate microglia activation: possible involvement of MAPK pathway

(A-C). Effects of RBE on the phosphorylation of p38MAPK, ERK, and JNK in non-activated microglia. Cells were treated with RBE (50–300 μg/ml) for 24 h followed by cell lyses and protein estimation. During stimulation, one of the wells in 6-well plate was incubated with LPS (10 ng/ml) for 30 min to be used as positive control to validate the functionality of antibodies against activated state of kinases. Whole cell lysates were subjected to western blots analyses. Representative blots (upper panel) and densitometry analyses (lower panel) are shown: A) p38 MAPK, B) pERK, and C) pJNK. Statistical analyses were carried out by using one-way ANOVA with post hoc Student-Newman-Keuls test (multiple comparisons). Results are expressed as means ± SEM of three independent experiments. *p < 0.05; **p < 0.01; ***p < 0.001 compared control cells. (TIF 963 kb

The integrin αvβ8 mediates epithelial homeostasis through MT1-MMP–dependent activation of TGF-β1

Întegrins, matrix metalloproteases (MMPs), and the cytokine TGF-β have each been implicated in homeostatic cell behaviors such as cell growth and matrix remodeling. TGF-β exists mainly in a latent state, and a major point of homeostatic control is the activation of TGF-β. Because the latent domain of TGF-β1 possesses an integrin binding motif (RGD), integrins have the potential to sequester latent TGF-β (SLC) to the cell surface where TGF-β activation could be locally controlled. Here, we show that SLC binds to αvβ8, an integrin expressed by normal epithelial and neuronal cells in vivo. This binding results in the membrane type 1 (MT1)-MMP–dependent release of active TGF-β, which leads to autocrine and paracrine effects on cell growth and matrix production. These data elucidate a novel mechanism of cellular homeostasis achieved through the coordination of the activities of members of three major gene families involved in cell–matrix interactions

Adult-Onset ANCA-Associated Vasculitis in SAVI: Extension of the Phenotypic Spectrum, Case Report and Review of the Literature.

STING-associated vasculopathy with onset in infancy (SAVI) is an autosomal dominant disorder due to gain-of-function mutations in STING1, also known as TMEM173, encoding for STING. It was reported as a vasculopathy of infancy. However, since its description a wider spectrum of associated manifestations and disease-onset has been observed. We report a kindred with a heterozygous STING mutation (p.V155M) in which the 19-year-old proband suffered from isolated adult-onset ANCA-associated vasculitis. His father suffered from childhood-onset pulmonary fibrosis and renal failure attributed to ANCA-associated vasculitis, and died at the age of 30 years due to respiratory failure. In addition, an overview of the phenotypic spectrum of SAVI is provided highlighting (a) a high phenotypic variability with in some cases isolated manifestations, (b) the potential of adult-onset disease, and (c) a novel manifestation with ANCA-associated vasculitis

Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials : a consensus study

Background: Current methodological guidelines provide advice about the assessment of sub-group analysis within RCTs, but do not specify explicit criteria for assessment. Our objective was to provide researchers with a set of criteria that will facilitate the grading of evidence for moderators, in systematic reviews. Method: We developed a set of criteria from methodological manuscripts (n = 18) using snowballing technique, and electronic database searches. Criteria were reviewed by an international Delphi panel (n = 21), comprising authors who have published methodological papers in this area, and researchers who have been active in the study of sub-group analysis in RCTs. We used the Research ANd Development/University of California Los Angeles appropriateness method to assess consensus on the quantitative data. Free responses were coded for consensus and disagreement. In a subsequent round additional criteria were extracted from the Cochrane Reviewers’ Handbook, and the process was repeated. Results: The recommendations are that meta-analysts report both confirmatory and exploratory findings for subgroups analysis. Confirmatory findings must only come from studies in which a specific theory/evidence based apriori statement is made. Exploratory findings may be used to inform future/subsequent trials. However, for inclusion in the meta-analysis of moderators, the following additional criteria should be applied to each study: Baseline factors should be measured prior to randomisation, measurement of baseline factors should be of adequate reliability and validity, and a specific test of the interaction between baseline factors and interventions must be presented. Conclusions: There is consensus from a group of 21 international experts that methodological criteria to assess moderators within systematic reviews of RCTs is both timely and necessary. The consensus from the experts resulted in five criteria divided into two groups when synthesising evidence: confirmatory findings to support hypotheses about moderators and exploratory findings to inform future research. These recommendations are discussed in reference to previous recommendations for evaluating and reporting moderator studies

Best practices for virtual participation in meetings : experiences from synthesis centers

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Social Conformity in Autism.

Humans are extremely susceptible to social influence. Here, we examine whether this susceptibility is altered in autism, a condition characterized by social difficulties. Autistic participants (N = 22) and neurotypical controls (N = 22) completed a memory test of previously seen words and were then exposed to answers supposedly given by four other individuals. Autistic individuals and controls were as likely to alter their judgements to align with inaccurate responses of group members. These changes reflected both temporary judgement changes (public conformity) and long-lasting memory changes (private conformity). Both groups were more susceptible to answers believed to be from other humans than from computer algorithms. Our results suggest that autistic individuals and controls are equally susceptible to social influence when reporting their memories

Multiple sclerosis risk variants alter expression of co-stimulatory genes in B cells.

The increasing evidence supporting a role for B cells in the pathogenesis of multiple sclerosis prompted us to investigate the influence of known susceptibility variants on the surface expression of co-stimulatory molecules in these cells. Using flow cytometry we measured surface expression of CD40 and CD86 in B cells from 68 patients and 162 healthy controls that were genotyped for the multiple sclerosis associated single nucleotide polymorphisms (SNPs) rs4810485, which maps within the CD40 gene, and rs9282641, which maps within the CD86 gene. We found that carrying the risk allele rs4810485*T lowered the cell-surface expression of CD40 in all tested B cell subtypes (in total B cells P ≤ 5.10 × 10-5 in patients and ≤4.09 × 10-6 in controls), while carrying the risk allele rs9282641*G increased the expression of CD86, with this effect primarily seen in the naïve B cell subset (P = 0.048 in patients and 5.38 × 10-5 in controls). In concordance with these results, analysis of RNA expression demonstrated that the risk allele rs4810485*T resulted in lower total CD40 expression (P = 0.057) but with an increased proportion of alternative splice-forms leading to decoy receptors (P = 4.00 × 10-7). Finally, we also observed that the risk allele rs4810485*T was associated with decreased levels of interleukin-10 (P = 0.020), which is considered to have an immunoregulatory function downstream of CD40. Given the importance of these co-stimulatory molecules in determining the immune reaction that appears in response to antigen our data suggest that B cells might have an important antigen presentation and immunoregulatory role in the pathogenesis of multiple sclerosis

PROTOCOLO DE CURATIVO EM FERIDAS CRÔNICAS: RELATO DE EXPERIÊNCIA

Introdução: Nos dias atuais, são frequentes discussões sobre a segurança do paciente seja em atenção de saúde primária, secundária ou terciária, com o objetivo de propor medidas para diminuir riscos e eventos adversos como por exemplo as lesões por pressão. Quando esse tipo de lesão já está instalada de forma crônica, são necessários cuidados básicos que são melhores instituídos com protocolos. Objetivo: relatar como o protocolo foi realizado e a sua importância para o cuidado em saúde. Métodos: relato de experiência de um Estágio Supervisionado Obrigatório realizado na 5ª fase do curso de Enfermagem em uma Unidade Básica de Saúde. Este protocolo foi elaborado com a finalidade de auxiliar na realização de curativos de feridas crônicas, quanto a sua avaliação, evolução e tipo de cobertura a ser escolhida. Resultados: em um primeiro momento foram estabelecidos critérios e normas gerais a serem seguidas para a realização do curativo, após essa etapa as feridas devem ser&nbsp;caracterizadas quanto a sua causa, quanto ao conteúdo microbiano, tipo de cicatrização, grau de abertura e tempo de duração. Além disso, é preciso saber reconhecer os tipos de tecido do leito da ferida pois indica a fase de cicatrização que a ferida se encontra, a evolução e a eficácia do tratamento. Conclusão: o intuito de trabalhar com um protocolo nas unidades de saúde consiste em padronizar técnicas de enfermagem, dessa forma, promovendo uma técnica de curativo segura que preserve o potencial de recuperação quando possível e minimize os riscos de trauma e/ou infecção