Leptin and advanced glycation end products receptor (RAGE) in tuberculosis patients

Introduction The pathogenesis of consumptive syndrome of tuberculosis (TB) is largely unknown. Leptin concentrations may be high because of the host’s inflammatory response, contributing to weight loss in patients with TB. The receptor for advanced glycation end products (RAGE) is also associated with weight loss in patients with TB and is related to enhanced mortality. The objective of this study was to evaluate the association between leptin and AGE/RAGE. Methods Case-control study. Leptin, AGE (carboxymethyl lysine, CML) and soluble RAGE (sRAGE) were measured from blood samples by ELISA. Results We included in the study 34 patients with TB and 34 controls. We found an inverse correlation between serum leptin levels and sRAGE, only in cases (r = -0.609, p < 0.0001). sRAGE levels were lower in patients with TB who died as compared with patients who survive (21.90 ± 4.24 pg/mL vs 66.14 ± 29.49 pg/mL; p = 0.045). Leptin levels were higher in patients with TB who died as compared with patients who survive (14.11 [7.48–14.11] ng/mL vs 3.08 [0.54–6.34] ng/mL; p = 0.028). Conclusions We identified lower sRAGE levels and higher leptin levels in patients with TB who died as compared with patients who survive. In addition, an inverse and significant correlation between serum leptin and sRAGE levels was demonstrated. Future studies, with a larger sample size and in different settings, including not only hospitalized patients, are needed to confirm these findings

Localizador de especialistas: uma plataforma tecnológica para a identificação e o compartilhamento do conhecimento dos interagentes de uma unidade de informação

Objetivo: Caracteriza-se como um estudo focado no desenvolvimento de um serviço tecnológico para bibliotecas universitárias baseado nos preceitos da biblioteca do futuro. Busca contribuir com o melhor aproveitamento do capital intelectual existente entre os membros da comunidade acadêmica, evitando assim o desperdício do recurso institucional na contratação de especialistas externos e melhorando a eficiência da instituição com a aproximação de grupos de interesse, possibilitando assim o desenvolvimento de trabalhos colaborativos. Objetiva relatar a experiência do desenvolvimento de um protótipo tecnológico denominado Localizador de Especialistas, concebido como um possível serviço a ser ofertado pelas bibliotecas universitárias à sua comunidade acadêmica. Método: Explicativa e descritiva quanto aos seus objetivos, a presente pesquisa aplicada utilizou-se do estudo de caso como procedimento técnico, pois buscou analisar profunda e exaustivamente as tecnologias disponíveis para proposição de um novo serviço e desenvolvimento do protótipo tecnológico. Resultados: Foram definidos os requisitos funcionais necessários para o funcionamento do sistema, posteriormente apresentou-se a ferramenta tecnológica desenvolvida por meio de um software de código aberto pré-existente e por fim a proposta de operacionalização do serviço. Conclusões: Conclui-se que o Localizador de Especialistas é um serviço viável para implementação em bibliotecas universitárias, pois é de baixo custo e rápida execução, extrapolando os serviços tradicionais da biblioteca e contribuindo para a construção coletiva e colaborativa do conhecimento

Pais ouvintes e filhos surdos: o lugar das famílias em propostas educacionais bilíngues

From the late twentieth century, researches intensify discussions about the foundational role of Sign Language in the educational development of deaf child. In Brazil, Brazilian Sign Language - Libras was officially recognized as the first language of the deaf community and its use and diffusion are guaranteed by legal documents that, in the same sense, provide for the education of the deaf to occur in a bilingual context. Deaf children born into deaf parents homes interact in Sign Language, naturally, like listeners in the auditory-oral language. Therefore, deaf children of hearing parents face difficulties in relating to family members if there is no opportunity to appropriate Sign Language at the suitable time, what interfers negatively in their linguistic and educational development. Although the role of family is made clear and established in legal documents and specific guidelines of the Ministry of Education and the Secretariat of Special Education, regarding the importance of Sing Language learning by family members, programs designed for this purpose, are goals to be pursued by Brazilian Schools. In this way, this study aims to analyze such implications, expanding the discussion about the need to offer family actions in bilingual educational programs that, among other aspects, defend the deaf child's right to interact in the world in/through Libras. In view of the above, it is believed that the Norwegian program Se mitt språk (See my language) can be a relevant reference for future and urgent actions in this regard, which could be verified based on qualitative analysis of observations and written records, through Diary Research, as well as promotional materials and report of the program, collected during a study group visit to that country, sponsored by the Rotary International Foundation.A partir do final do século XX, pesquisas intensificam as discussões sobre o papel fundante da Língua de Sinais no desenvolvimento educacional da criança surda. No Brasil, a Língua Brasileira de Sinais - Libras foi reconhecida, oficialmente, como a primeira língua da comunidade surda, e seu uso e divulgação garantidos por documentos legais que, no mesmo sentido, preveem que a educação do surdo ocorra em contexto bilíngue. As crianças surdas que nascem em lares de pais surdos interagem em Língua de Sinais, naturalmente, como os ouvintes, na língua oral-auditiva. Por conseguinte, crianças surdas, filhas de pais ouvintes, enfrentam dificuldades para se relacionar com os membros da família, caso não haja oportunidade de apropriação da Língua de Sinais, no tempo adequado, o que interfere, negativamente, em seu desenvolvimento linguístico e educacional. Embora o papel da família seja claramente estabelecido em documentos legais e de orientações específicas do Ministério da Educação e da Secretaria de Educação Especial, explicitando a importância da aprendizagem desta língua pelos familiares, pouca ação tem sido dirigida para esse fim, nas escolas brasileiras. Nesse sentido, este estudo tem por objetivo discorrer sobre tais implicações, ampliando a discussão sobre a necessidade da oferta de ações destinadas à família, em programas educacionais bilíngues que, dentre outros aspectos, defendam o direito da criança surda interagir no mundo na/pela Libras. Diante do exposto, acredita-se que o programa norueguês Se mitt språk (Veja minha língua) pode se constituir como relevante referência para futuras e urgentes ações nesse sentido, o que foi possível constatar, a partir de análise qualitativa de observações e registros, por meio de Diário de Campo, bem como por materiais de divulgação e relatório sobre o programa, colhidos durante visita de grupo de estudos ao referido país, patrocinada pela fundação Rotary International

CONTRACEPTION IN ADOLESCENCE: A MATTER OF SELF-CARE

Objetivo: Sensibilizar adolescentes sobre a importância do autocuidado na prevenção da gravidez. Metodologia: Estudo qualitativo-descritivo utilizando a Pesquisa Convergente – Assistencial, ocorreu em dois momentos: uma oficina educativa sobre sexualidade e contraceptivos; e consultas de enfermagem com 10 adolescentes em um Centro de Saúde de São José-SC. Resultados e Disussão: As oficinas refletem que as adolescentes conhecem a pílula e o condom, mas tem pouco conhecimento sobre os demais, e sobre a sexualidade em geral. As consultas de enfermagem fomentaram os temas: perfil dos adolescentes, padrão da vida sexual, conhecimento sobre o corpo, conhecimento sobre os métodos contraceptivos, orientações recebidas sobre os métodos contraceptivos. Conclusão: Considera-se que os conhecimentos durante as atividades educativas tanto na escola, quanto no centro de saúde foram importantes para o autocuidado a saúde sexual e reprodutiva, mas insuficientes para mudar o comportamento deste grupo quanto à adoção de práticas sexuais seguras

CONTRACEPTION IN ADOLESCENCE: A MATTER OF SELF-CARE

Objetivo: Sensibilizar adolescentes sobre a importância do autocuidado na prevenção da gravidez. Metodologia: Estudo qualitativo-descritivo utilizando a Pesquisa Convergente – Assistencial, ocorreu em dois momentos: uma oficina educativa sobre sexualidade e contraceptivos; e consultas de enfermagem com 10 adolescentes em um Centro de Saúde de São José-SC. Resultados e Disussão: As oficinas refletem que as adolescentes conhecem a pílula e o condom, mas tem pouco conhecimento sobre os demais, e sobre a sexualidade em geral. As consultas de enfermagem fomentaram os temas: perfil dos adolescentes, padrão da vida sexual, conhecimento sobre o corpo, conhecimento sobre os métodos contraceptivos, orientações recebidas sobre os métodos contraceptivos. Conclusão: Considera-se que os conhecimentos durante as atividades educativas tanto na escola, quanto no centro de saúde foram importantes para o autocuidado a saúde sexual e reprodutiva, mas insuficientes para mudar o comportamento deste grupo quanto à adoção de práticas sexuais seguras

Mechanisms of oxygenation responses to proning and recruitment in COVID-19 pneumonia

Purpose This study aimed at investigating the mechanisms underlying the oxygenation response to proning and recruitment maneuvers in coronavirus disease 2019 (COVID-19) pneumonia. Methods Twenty-five patients with COVID-19 pneumonia, at variable times since admission (from 1 to 3 weeks), underwent computed tomography (CT) lung scans, gas-exchange and lung-mechanics measurement in supine and prone positions at 5 cmH(2)O and during recruiting maneuver (supine, 35 cmH(2)O). Within the non-aerated tissue, we differentiated the atelectatic and consolidated tissue (recruitable and non-recruitable at 35 cmH(2)O of airway pressure). Positive/negative response to proning/recruitment was defined as increase/decrease of PaO2/FiO(2). Apparent perfusion ratio was computed as venous admixture/non aerated tissue fraction. Results The average values of venous admixture and PaO2/FiO(2) ratio were similar in supine-5 and prone-5. However, the PaO2/FiO(2) changes (increasing in 65% of the patients and decreasing in 35%, from supine to prone) correlated with the balance between resolution of dorsal atelectasis and formation of ventral atelectasis (p = 0.002). Dorsal consolidated tissue determined this balance, being inversely related with dorsal recruitment (p = 0.012). From supine-5 to supine-35, the apparent perfusion ratio increased from 1.38 +/- 0.71 to 2.15 +/- 1.15 (p = 0.004) while PaO2/FiO(2) ratio increased in 52% and decreased in 48% of patients. Non-responders had consolidated tissue fraction of 0.27 +/- 0.1 vs. 0.18 +/- 0.1 in the responding cohort (p = 0.04). Consolidated tissue, PaCO2 and respiratory system elastance were higher in patients assessed late (all p < 0.05), suggesting, all together, "fibrotic-like" changes of the lung over time. Conclusion The amount of consolidated tissue was higher in patients assessed during the third week and determined the oxygenation responses following pronation and recruitment maneuvers

Exploiting the 2-Amino-1,3,4-thiadiazole Scaffold To Inhibit <i>Trypanosoma brucei </i>Pteridine Reductase in Support of Early-Stage Drug Discovery

Pteridine reductase-1 (PTR1) is a promising drug target for the treatment of trypanosomiasis. We investigated the potential of a previously identified class of thiadiazole inhibitors of Leishmania major PTR1 for activity against Trypanosoma brucei (Tb). We solved crystal structures of several TbPTR1-inhibitor complexes to guide the structure-based design of new thiadiazole derivatives. Subsequent synthesis and enzyme- and cell-based assays confirm new, mid-micromolar inhibitors of TbPTR1 with low toxicity. In particular, compound 4m, a biphenyl-thiadiazole-2,5-diamine with IC50 = 16 μM, was able to potentiate the antitrypanosomal activity of the dihydrofolate reductase inhibitor methotrexate (MTX) with a 4.1-fold decrease of the EC50 value. In addition, the antiparasitic activity of the combination of 4m and MTX was reversed by addition of folic acid. By adopting an efficient hit discovery platform, we demonstrate, using the 2-amino-1,3,4-thiadiazole scaffold, how a promising tool for the development of anti-T. brucei agents can be obtained

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist