IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP) located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and also the influence of this SNP in the secretion of IFN-γ <it>in vitro</it>.</p> <p>Methods</p> <p>Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). <it>Leishmania</it>-induced IFN-γ production on peripheral blood mononuclear cell (PBMC) culture supernatants was assessed by ELISA.</p> <p>Results</p> <p>There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers.</p> <p>Conclusion</p> <p>Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.</p

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia

Cuidados nos pacientes com hemofilia e doença de von Willebrand na cirurgia eletiva otorrinolaringológica Otolaryngology surgery: management of elective surgery in patients with haemophilia and von Willebrand disease

FORMA DE ESTUDO Clínico prospectivo. MATERIAL E MÉTODO: Foi realizado um estudo prospectivo de 10 anos de 20 pacientes com hemofilias ou doença de von Willebrand (DvW) com indicação de cirurgia otorrinolaringológica. Os pacientes foram submetidos a um total de 25 cirurgias otorrinolaringológicas eletivas. A idade média foi de 23,75 anos (2 a 62 anos). O grupo de estudo consistiu em 14 hemofílicos, 11 com hemofilia A grave (1 do sexo feminino), uma portadora com 30% de atividade de fator VIII (FVIII), um hemofílico B leve e uma com deficiência grave de fator X; 6 com DvW, 4 tinham o tipo 1 (3 mulheres), um o tipo 2A e um o tipo 3. Treze hemofílicos tinham síndrome de imunodeficiência adquirida. A duração média do procedimento foi de 1 hora e 37 minutos (15 minutos a 12 horas). O defeito da coagulação foi corrigido com desmopressina (DDAVP), com concentrado de FVIII de pureza intermediária 8Y, com criopreciptado ou com complexo protrombínico não ativado (PPSB), de acordo com os níveis plasmáticos do fator e da severidade da cirurgia. O ácido épsilon aminocapróico também foi usado em associação. Em 1 hemofílico A grave houve sangramento pós-operatório que se resolveu com a elevação do nível mínimo de FVIII para 80% e em 1 paciente com DvW do Tipo 3 houve sangramento pós-operatório pela dificuldade de identificação do melhor concentrado a ser reposto. Após o uso do concentrado de pureza intermediária 8Y, houve controle do sangramento. RESULTADO: Todos os outros pacientes apresentaram a hemostasia considerada normal ou excelente. CONCLUSÃO: Concluiu-se que pacientes com hemofilias ou DvW não apresentam um risco cirúrgico aumentado se for realizada uma terapia adequada.<br>STUD DESIGN: Clinical prospective. MATERIAL AND METHOD: A 10-year prospective research was conducted in 20 patients with hemophilia or von Willebrand disease (vWD). They were submitted to a total of 25 elective otolaryngological surgical events. The average age of the patients was 23.75 years (2-62 years). The study group consisted of 14 hemophiliacs, 11 with severe hemophilia A (1 female), 1 female with 30% of VIII factor (VIIIF) level, 1 male with hemophilia B and 1 female with severe factor X deficiency; and 6 with vWD, 4 type 1 (3 females), 1 male type 2 A and 1 male type 3. Acquired immunodeficiency syndrome was present in 13 hemophilic patients. The mean duration of the surgical events was 1 hour and 37 minutes (15 min-12 hours). The coagulation defect was corrected with desmopressin (DDAVP), intermediate purity VIIIF concentrate 8Y, cryoprecipitated or non-activated prothrombinic complex (PPSB), according to factor levels and the severity of the surgery. Epsilon aminocaproic acid was used in association. In 1 severe hemophiliac A patient, excessive bleeding was observed in the second day of the postoperative period which ceased with elevation of the minimal level of VIIIF to 80%. In another patient, with type 3 vWD, severe postoperative bleeding occurred because of difficulty to identify the best reposition blood coagulation factor for him. After the use of intermediate purity VIIIF concentrate 8Y, the bleeding was controlled. RESULTS: The hemostatic effect in the other patients was rated as normal or excellent. CONCLUSION: It was concluded that patients with vWD or hemophilia do not have an increased operative risk if appropriate therapy is given

Empresariado industrial e a educação profissional brasileira Industrial businessmen and the Brazilian professional education

Considerando as mudanças políticas e econômicas transcorridas na sociedade brasileira na última década do século passado, marcadas, entre outros fatos, pela ascensão da ideologia neoliberal e por mudanças no setor produtivo, além da ênfase discursiva de governo e de setores empresariais sobre a necessária reformulação do sistema educacional visando o alcance de uma economia competitiva, objetiva-se analisar o papel que o empresariado industrial reserva à educação profissional visando a consecução do seu projeto de desenvolvimento econômico. Foram utilizados como fontes primárias documentos técnicos da Confederação Nacional da Indústria (CNI) e da Federação das Indústrias do Estado de São Paulo (Fiesp), além de depoimentos das lideranças dessas instituições em diversos periódicos brasileiros. Concluiu-se que embora o empresariado brasileiro tenha enfatizado o investimento na educação básica e na educação profissional, tal ênfase busca ajustar a educação brasileira aos interesses econômicos e não considerá-la um direito social a ser garantido pelo Estado a todos cidadãos brasileiros. As análises e proposições do empresariado para a educação estruturam-se em bases semelhantes às proferidas pelo Banco Mundial, o qual segue enfaticamente a Teoria do Capital Humano. Afirma-se também que suas proposições concernentes ao desenvolvimento econômico e à política educacional foram incorporadas na agenda do governo central brasileiro no transcorrer da década de 1990.<br>Considering the political and economical changes that took place in the Brazilian society during the last decade of the 20th century, characterized as they were, among other facts, by the rising of the neoliberal ideology and by changes in the productive sector, apart from the professed emphasis government and business sectors have placed on the necessary reform of the education system aimed at achieving a competitive economy, the objective of this article is to investigate the role industrial businessmen assign to professional education within their projects of economic development. The primary reference material used were technical documents by the Confederação Nacional da Indústria (CNI - National Confederation of Industries) and by the Federação das Indústrias do Estado de São Paulo (Fiesp - Industry Federation of the State of São Paulo), and also testimonies from leaders of those institutions extracted from various Brazilian periodicals. The conclusion has been that although Brazilian businessmen have emphasized investments in basic and professional education, such emphasis seeks to adjust education in Brazil to economic interests and not to regard it as a social right to be guaranteed by the state to all citizens. The analyses and proposals for education made by businessmen evolve around principles similar to those put forward by the World Bank, which adhere strictly to the Theory of Human Capital. The text also shows that such proposals regarding economic development and educational policy have been incorporated into the Brazilian central government agenda during the 1990s