Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents

OBJECTIVES: To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC). METHODS: HI patients (n=12), aged 8–17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3–10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1–18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits. RESULTS: The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/ no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells. CONCLUSION: The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients

Endogenously-expressed NH2-terminus of circumsporozoite protein interferes with sporozoite invasion of mosquito salivary glands

Abstract\ud \ud Background\ud The circumsporozoite protein is the most abundant polypeptide expressed by sporozoites, the malaria parasite stage capable of infecting humans. Sporozoite invasion of mosquito salivary glands prior to transmission is likely mediated by a receptor/ligand-like interaction of the parasites with the target tissues, and the amino (NH2)-terminal portion of CSP is involved in this interaction but not the TSR region on the carboxyl (C)-terminus. Peptides based on the NH2-terminal domain could compete with the parasites for the salivary gland receptors and thus inhibit penetration.\ud \ud \ud Methods\ud Peptides based on the NH2-terminus and TSR domains of the CSP from avian or human malaria parasites, Plasmodium gallinaceum and Plasmodium falciparum, respectively, were expressed endogenously in mosquito haemolymph using a transient (Sindbis virus-mediated) or stable (piggyBac-mediated transgenesis) system.\ud \ud \ud Results\ud Transient endogenous expression of partial NH2-terminus peptide from P. falciparum CSP in P. gallinaceum-infected Aedes aegypti resulted in a reduced number of sporozoites in the salivary glands. When a transgenic approach was used to express a partial CSP NH2-terminal domain from P. gallinaceum the number of sporozoites in the salivary glands did not show a difference when compared to controls. However, a significant difference could be observed when mosquitoes with a lower infection were analysed. The same result could not be observed with mosquitoes endogenously expressing peptides based on the TSR domain from either P. gallinaceum or P. falciparum.\ud \ud \ud \ud Conclusion\ud These results support the conclusion that CSP partial NH2-terminal domain can be endogenously expressed to promote a competition for the receptor used by sporozoites to invade salivary glands, and they could be used to block this interaction and reduce parasite transmission. The same effect cannot be obtained with peptides based on the TSR domain.We thank Neuza Saraiva Fernandes and Ediane Saraiva Fernandes for technical\ud assistance and Alexandre Santos de Moura for sample sequencing. This work\ud was supported by FAPESP (Process#04/00889-9 and#00/12138-7). AAJ was\ud supported in part by an award from the National Institute of Allergy and Infec‑\ud tious Diseases (USA) (R37AI029746)

Laboratórios Remotos no Ensino de Engenharia

O presente capítulo contém uma seleção de artigos que foram apresentados na Sessão Dirigida: Laboratórios remotos no ensino da engenharia, realizada durante o XLIV Congresso Brasileiro de Educação em Engenharia (COBENGE), de 27 a 30 de setembro de 2016, em Natal, Rio Grande do Norte. Essa Sessão Dirigida propôs mostrar trabalhos que viessem a apresentar experiências baseadas em laboratórios remotos no ensino de engenharia, a fim de discutir e demonstrar as práticas ou técnicas propostas pelos grupos em diferentes realidades. Buscou, assim, expor pontos positivos e negativos para potenciais disseminações de projetos com semelhantes contextos. Portanto, o objetivo da Sessão Dirigida foi proporcionar um ambiente para discussão e reflexão referente à integração dos laboratórios remotos no ensino de engenharia. Os cinco artigos apresentados neste capítulo foram selecionados entre aqueles que receberam a qualificação a partir da apresentação oral na Sessão Dirigida ou como convidados. O primeiro, escrito por Thiago Schaedler Uhlmann e Luciano Antonio Mendes, da Pontifícia Universidade Católica do Paraná (PUC-PR), é intitulado “Jogos remotos: perspectivas de aplicação conjunta de aprendizagem baseada em jogos e experimentação remota no ensino de engenharia”. Tem como objetivo geral identificar possibilidades acerca do emprego da Aprendizagem Baseada em Jogos, associada a recursos de experimentação remota, no ensino de engenharia. O segundo artigo selecionado foi escrito por Ana M. B. Pavani; Delberis A. Lima; Guilherme P Temporão; Vanessa A. P. Lima, vinculados à Pontifícia Universidade Católica do Rio de Janeiro (PUC-RIO). O documento, intitulado “Implantação de um laboratório remoto: um projeto de múltiplas facetas”, busca descrever a experiência de iniciar a implantação de um laboratório remoto nessa instituição, no âmbito do Projeto VISIR+. O terceiro artigo, “Projetos de experimentos remotos como estratégia for- mativa para estudantes de engenharia”, foi escrito por Eduardo Kojy Takahashi; Rubens Gedraite; Hermes Gustavo Fernandes Neri; Dayane Carvalho Cardoso e Rener Martins de Moura, da Universidade Federal de Uberlândia (UFU). Os autores buscam apresentar uma possibilidade metodológica de formação básica de estudantes de engenharia, a partir do desenvolvimento colaborativo de projetos envolvendo experimentação remota e com o engajamento de professores-pesquisadores, estudantes de engenharia e estudantes do ensino médio que apresentem um potencial para a carreira de engenharia. O quarto artigo, intitulado “Percepções acerca de experimentos remotos no contexto de um curso de especialização em Educação em Engenharia e Ciências Exatas”, foi escrito por Luciano Andreatta Carvalho da Costa, da Universidade Estadual do Rio Grande do Sul (UERGS). No documento, o autor busca apresentar as percepções dos estudantes de um curso de especialização em Educação em Engenharia e em Ciências Exatas na UERGS, no âmbito da utilização de laboratórios remotos, a partir de uma disciplina ministrada no curso que trata do tema dos experimentos online e seus impactos para a formação na área tecnológica. O quinto artigo, “Programa de cooperação interinstitucional para experimentação remota nos processos de ensino e de aprendizagem de engenharia”, é de autoria de Gabriela Rocha Roque (Faculdade SATC); Josiel Pereira e Simone Meister Sommer Bilessimo, da Universidade Federal de Santa Catarina (UFSC). O documento descreve a uma iniciativa de cooperação entre duas instituições de ensino superior, a UFSC e a Faculdade SATC. Cooperação esta motivada pela integração de tecnologia no ensino de engenharia, através da utilização e do compartilhamento dos recursos de laboratórios de experimentação remota.info:eu-repo/semantics/publishedVersio

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

The Global Burden of Diseases, Injuries and Risk Factors 2017 includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. METHODS: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting