T lymphocytes, natural killer cells, cytotoxicity activity and vaccine response in HIV-exposed uninfected infants

Orientador: Maria Marluce dos Santos VilelaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: Uso de antiretrovirais pela gestante, parto cesárea na 38ª semana de gestação, administração intravenosa de zidovudina durante o parto e por via oral para o recém-nascido além de não aleitamento materno são medidas empregadas com sucesso para reduzir a transmissão vertical do HIV. Essas recomendações, associadas ao ambiente intrauterino alterado pela infecção materna, interferem no crescimento e desenvolvimento do feto/embrião podendo levar a disfunção mitocondrial e alterações hematológicas e imunológicas. O presente trabalho incluiu, no estudo referido como capítulo I, 33 lactentes com exposição vertical ao HIV não infectados (ENI) e 47 lactentes não expostos ao vírus (NE) e, no estudo referido no capítulo II, 51 ENI e 112 NE, todos com mediana de idade de 7 meses. Comparamos ENI e NE em relação ao peso de nascimento, à contagem de linfócitos TCD3, TCD4+, TCD8+, CD3-CD16+CD56+ (natural killer), atividade citotóxica de células mononucleares do sangue periférico para células tumorais K562 e resposta humoral para as vacinas hepatite B, difteria e tétano (Instituto Butantan-SP, Brasil). Os resultados mostram baixo peso ao nascimento e reduzida contagem de linfócitos TCD3, TCD4+ e TCD8+ entre os lactentes do grupo ENI. Resultados inéditos desse estudo foram uma reduzida resposta protetora à vacina da hepatite B, títulos baixos de anticorpos IgG para o toxóide tetânico e normais para o toxóide diftérico para os lactentes ENI. Além disso, encontramos para esse grupo uma contagem normal de células natural killer e preservada atividade citotóxica de células mononucleares do sangue periférico. Concluímos que o grupo de lactentes jovens ENI apresenta baixo peso ao nascer e alteração no desenvolvimento da imunidade adaptativa, necessitando de orientação específica para o calendário de vacinação.Abstract: Use of antiretroviral drugs by the pregnant woman, cesarean delivery at 38 weeks of gestation, intravenous zidovudine during delivery and orally to the newborn, in addition to not breastfeeding, are recommendations used successfully to reduce vertical transmission of HIV. These recommendations, coupled with the intrauterine environment altered by maternal infection, interfere with growth and development of the fetus/ embryo and may lead to mitochondrial dysfunction and hematological and immunological changes. In the study referred to as Chapter I were included 33 HIV-exposed uninfected infants (HEU) and 47 healthy infants not exposed to the virus (NE) and in the study referred to as Chapter II, 51 ENI and 112 NE, all of them with median age of 7 months. We compared HEU and NE with respect to birth weight, TCD3 lymphocyte, CD4+, CD8+ and CD3-CD16+CD56+ (natural killer) counts, cytotoxic activity of peripheral blood mononuclear cells against tumor cells K562 and humoral response to hepatitis B, diphtheria and tetanus vaccine (Instituto Butantan, SP, Brazil). The results show low birth weight and reduced lymphocyte count TCD3, CD4 + and CD8 + among infants of the HEU group. Inedited results of this study were a reduced protective response to hepatitis B vaccine, lower antitetanus titres of and normal anti-diphtheria titres for the HEU infants. Furthermore, we observed to the HEU group a normal count of natural killer cells and preserved cytotoxic activity of the peripheral blood mononuclear cells. We conclude that the group of HEU young infants has a low birth weight and changes in the development of adaptive immunity, requiring specific guidance for the vaccination schedule.MestradoSaude da Criança e do AdolescenteMestre em Saude da Criança e do Adolescent

The pluriactive development of agricultural holdings in Poland with regard to the living standards of their users

This paper illustrates the regional diversity in terms of the agricultural income of economically weak farms in Poland (i.e. from 2 to 8 ESU). The results, expressed as average values for 2005-2009, indicate that farms are finding themselves in a very difficult situation. Furthermore, the assessment included farms that gained their income not only through agricultural activity, but also through doing non-agricultural work. The diversification of income sources created the opportunity to sustain less profitable agricultural production while providing a higher standard of living for farmers and their families. Such factors as the intensity of production, and the productiveness of current expenditures and fixed capital, as well as the financial position of the farms and the level of their debt, have been analysed. An important aim of the study was to identify the influence of the Common Agricultural Policy on the performance of farms

EU Kids Online 2020: technical report

This report describes in detail the methodology used for the EU Kids Online IV project (see the description of the four phases of the project in the next section). Within this project, a large-scale survey of children aged 9–17 from 19 European countries was conducted. The data were collected between autumn 2017 and summer 2019 from 25,101 children by national teams from the EU Kids Online network. This report provides information about the nature of the project, how the questionnaire was developed, sampling and data collection, ethical issues, data management and weighting. The information in this report should enable dataset users to understand the logic and nature of the survey. For dataset users, we also recommend using the ‘Data Dictionary’ (available at eukidsonline.net), a related document that systematically maps all the information related to the data in the dataset. Moreover, Annex 2 of this report provides concise key guidelines for dataset users. We highly recommend using these short guidelines during work with the EU Kids Online 2020 dataset. Annex 3 contains a description of the key variables. Full questionnaires and their national forms are available at eukidsonline.net

a challenge for current therapeutic strategies

Background The defects in DNA repair genes are potentially linked to development and response to therapy in medulloblastoma. Therefore the purpose of this study was to establish the spectrum and frequency of germline variants in selected DNA repair genes and their impact on response to chemotherapy in medulloblastoma patients. Methods The following genes were investigated in 102 paediatric patients: MSH2 and RAD50 using targeted gene panel sequencing and NBN variants (p.I171V and p.K219fs*19) by Sanger sequencing. In three patients with presence of rare life-threatening adverse events (AE) and no detected variants in the analyzed genes, whole exome sequencing was performed. Based on combination of molecular and immunohistochemical evaluations tumors were divided into molecular subgroups. Presence of variants was tested for potential association with the occurrence of rare life-threatening AE and other clinical features. Results We have identified altogether six new potentially pathogenic variants in MSH2 (p.A733T and p.V606I), RAD50 (p.R1093*), FANCM (p.L694*), ERCC2 (p.R695C) and EXO1 (p.V738L), in addition to two known NBN variants. Five out of twelve patients with defects in either of MSH2, RAD50 and NBN genes suffered from rare life-threatening AE, more frequently than in control group (p = 0.0005). When all detected variants were taken into account, the majority of patients (8 out of 15) suffered from life- threatening toxicity during chemotherapy. Conclusion Our results, based on the largest systematic study performed in a clinical setting, provide preliminary evidence for a link between defects in DNA repair genes and treatment related toxicity in children with medulloblastoma. The data suggest that patients with DNA repair gene variants could need special vigilance during and after courses of chemotherapy

Logistic network profitability analysis: a new computing method

Este artigo apresenta um método de cálculo de rentabilidade econômica de unidades operacionais (UOs) de empresas de transporte de carga fracionada que operam através de uma rede logística com múltiplas UOs. O cálculo da rentabilidade econômica de cada uma destas UOs é um problema complexo. Devido ao intercâmbio de cargas entre UOs, as receitas de uma UO estão interligadas com as receitas de outras UOs. Os métodos tradicionais de contabilização enfrentam dificuldades quando empregados para determinar a rentabilidade econômica de UOs de uma rede logística de UOs interdependentes. O método descrito neste artigo elimina estas dificuldades por meio do conceito de margem de contribuição.This paper offers a method for evaluating the profitability of operation sites (OS) of less-than-truckload (LTL) carriers conveying shipments through a network with multiple OS. The evaluation of the profitability of each one of these OS is a complex problem. Due to exchanges of shipments between OS, the revenues of one OS are intertwined with the revenues of other OS. Traditional accounting methods show themselves cumbersome when employed to evaluate the profitability of OS of a logistical network of interdependent OS. The method described in this paper overcomes these difficulties by means of the concept of contribution margin