CAMINHANDO - Implementação do Tratado de Marraqueche para pessoas cegas, com deficiência visual ou com outras dificuldades para ter acesso ao texto impresso: um guia prático para bibliotecários

No período de maio a julho de 2020, a Secretaria Especial da Cultura (SECULT) abriu consulta pública2 para coleta de informações, sugestões e comentários da sociedade a respeito da minuta de Decreto para a regulamentação do Tratado de Marraqueche. O Tratado, que foi promulgado no Brasil pelo Decreto nº 9.522, de 8 de outubro de 2018, visa facilitar o acesso a obras publicadas às pessoas cegas, com deficiência visual ou com outras dificuldades para acesso ao texto impresso. Entendendo que a participação das bibliotecas brasileiras é crucial neste momento e visando oferecer-lhes recursos qualificados e aprimorados para consulta e atualização no tema, a Comissão Brasileira de Direitos de Autor e Acesso Aberto (CBDA3) da Federação Brasileira de Associações de Bibliotecas, Cientistas da Informação e Instituições (FEBAB) se responsabilizou pela tradução deste Manual da IFLA e, também, por sua adaptação à minuta em discussão na já referida consulta pública. Deste modo, trata-se de uma obra de caráter provisório, que poderá ser útil especificamente neste momento, mas que deverá ser atualizada tão logo o decreto seja definitivamente aprovado no país. Esperamos que nossos profissionais possam sanar suas dúvidas e se sintam motivados a participar de maneira pró ativa e objetiva da Consulta Aberta em andamento. Sueli Mara Soares Pinto Ferreira Presidente da Comissão Brasileira de Direitos de Autor e Acesso Aberto – CBDA3 Federação Brasileira de Associações de Bibliotecas, Cientista da Informação e Instituições - FEBAB São Paulo, Brasil Junho 202

Role of Tumor Necrosis Factor-α in the Human Systemic Endotoxin-Induced Transcriptome

<div><p>TNFα has been implicated in the pathogenesis of various inflammatory diseases. Different strategies to inhibit TNFα in patients with sepsis and chronic inflammatory conditions have shown contrasting outcomes. Although TNFα inhibitors are widely used in clinical practice, the impact of TNFα antagonism on white blood cell gene expression profiles during acute inflammation in humans <i>in vivo</i> has not been assessed. We here leveraged the established model of human endotoxemia to examine the effect of the TNFα antagonist, etanercept, on the genome-wide transcriptional responses in circulating leukocytes induced by intravenous LPS administration in male subjects. Etanercept pre-treatment resulted in a markedly dampened transcriptional response to LPS. Gene co-expression network analysis revealed this LPS-induced transcriptome can be categorized as TNFα responsive and non-responsive modules. Highly significant TNFα responsive modules include NF-kB signaling, antiviral responses and T-cell mediated responses. Within these TNFα responsive modules we delineate fundamental genes involved in epigenetic modifications, transcriptional initiation and elongation. Thus, we provide comprehensive information about molecular pathways that might be targeted by therapeutic interventions that seek to inhibit TNFα activity during human inflammatory diseases.</p></div

Early functional and transcriptomic changes in the myocardium predict outcome in a long-term rat model of sepsis

Myocardial function is depressed in sepsis and is an important prognosticator in the human condition. Using echocardiography in a long-term fluid-resuscitated Wistar rat model of faecal peritonitis we investigated whether depressed myocardial function could be detected at an early stage of sepsis and, if so, whether the degree of depression could predict eventual outcome. At 6 h post-insult, a stroke volume <0.17 ml prognosticated 3-day mortality with positive and negative predictive values of 93 and 80%, respectively. Subsequent fluid loading studies demonstrated intrinsic myocardial depression with poor-prognosis animals tolerating less fluid than either good-prognosis or sham-operated animals. Cardiac gene expression analysis at 6 h detected 527 transcripts significantly up- or down-regulated by the septic process, including genes related to inflammatory and cell cycle pathways. Predicted mortality was associated with significant differences in transcripts of genes expressing proteins related to the TLR2/MyD88 (Toll-like receptor 2/myeloid differentiation factor 88) and JAK/STAT (Janus kinase/signal transducer and activator of transcription) inflammatory pathways, β-adrenergic signalling and intracellular calcium cycling. Our findings highlight the presence of myocardial depression in early sepsis and its prognostic significance. Transcriptomic analysis in heart tissue identified changes in signalling pathways that correlated with clinical dysfunction. These pathways merit further study to both better understand and potentially modify the disease process

TNFα responsive module hub (driver) genes and co-expression network visualization.

<p>Genes within transcriptional modules can be categorized as peripheral or hubs on the basis of how correlated a gene is with all other genes in the network, defined as the genes' connectivity measure, <b>k</b>. High intramodulr connectivities denote highly important module genes oftentimes possessing transcriptional factor activity. <b>A</b>. Unsupervised hierarchical clustering heatmap plot of the TNFα responsive module hub genes. Red denotes high expression; blue denotes low expression. The relative importance of each module within the co-expression network can be highlighted by unsupervised visualizations of each genes' weighted correlation coefficient. This was implemented in the Cytoscape® platform <b>B</b>. TNFα responsive co-expression modules were visualized by an organic layout considering weighted correlation coefficients >0.1 (equivalent to correlation coefficient >0.9).</p

Functional annotation and hub genes for the LPS-induced co-expression modules.

<p>LPS-induced transcriptome is organized into 38 co-expression network modules. Each module was analyzed for enrichment of biological pathways by IPA (Ingenuity® systems, <a href="http://www.ingenuity.com" target="_blank">www.ingenuity.com</a>).</p

Genomic analysis of the systemic LPS-induced transcriptional response and impact of TNFα inhibition.

<p><b>A</b>. Volcano plot analysis (integrating p-values and log2 foldchanges) for the LPS-induced response in subjects treated with placebo. <b>B</b>. Volcano plot analysis of the LPS-induced response in subjects treated with the TNFα antagonist etanercept. Red dots in panels A and B indicate probes that showed a fold-change ≥1.5 or ≤1.5. <b>C</b>. Unsupervised hierarchical clustering heatmap of the 4077 LPS-induced transcripts that were influenced by etanercept treatment as identified by ANOVA (q-value <0.05). Columns represent subject samples and rows represent transcripts. Red indicates increased gene expression, and blue indicates decreased gene expression.</p

LPS-induced TNFα responsive module genes linked to transcriptional initiation, elongation and epigenetic regulation.

<p>Genes within LPS-induced TNFα responsive co-expression modules possessing epigenetic regulation, transcriptional initiation and elongation properties. kTotal, total connectivity, k. kWithin, intra-modular connectivity. kOut, extra-modular connectivity. <i>log2</i> FC LPS, log2 transformed foldchange for the placebo-treated pre- and post-LPS challenged samples. <i>log2</i> FC LPS+Etan, log2 transformed foldchange for the etanercept-treated pre- and post-LPS challenged samples. Gene names marked in bold type denote module genes identified as top module hub genes.</p