A subunit vaccine based on biodegradable microspheres carrying rHsp65 protein and KLK protects BALB/c mice against tuberculosis infection

Of the hundreds of new tuberculosis ( TB) vaccine candidates some have therapeutic value in addition to their prophylactic properties. This is the case for the DNA vaccine encoding heat-shock protein 65 (DNAhsp65) from Mycobacterium leprae. However, there are concerns about the use of DNA vaccines in certain populations such as newborns and pregnant women. Thus, the optimization of vaccination strategies that circumvent this limitation is a priority. This study evaluated the efficacy of a single dose subunit vaccine based on recombinant Hsp65 protein against infection with M. tuberculosis H37Rv. The Hsp65 protein in this study was either associated or not with immunostimulants, and was encapsulated in biodegradable PLGA microspheres. Our results demonstrate that the protein was entrapped in microspheres of adequate diameter to be engulfed by phagocytes. Mice vaccinated with a single dose of Hsp65-microspheres or Hsp65 + CpG-microspheres developed both humoral and cellular-specific immune responses. However, they did not protect mice against challenge with M. tuberculosis. By contrast, Hsp65+KLK-microspheres induced specific immune responses that reduced bacilli loads and minimized lung parenchyma damage. These data suggest that a subunit vaccine based on recombinant protein Hsp65 is feasible.

Dissemination of bla(KPC-2) by the Spread of Klebsiella pneumoniae Clonal Complex 258 Clones (ST258, ST11, ST437) and Plasmids (IncFII, IncN, IncL/M) among Enterobacteriaceae Species in Brazil

This article reports the spread of bla(KPC-2) in the Sao Paulo and Rio de Janeiro states, facilitated by globally spread K. pneumoniae clonal complex 258 (CC258) clones (ST258, ST11, and ST437) and a diversity of plasmids (IncFII, IncN, and IncL/M, two untypeable plasmids carrying Tn4401a or Tn4401b) successfully disseminated among species of the Enterobacteriaceae (Enterobacter cloacae, Serratia marcescens, and Citrobacter freundii). It also constitutes the first description of sequence type 258 (ST258) in Brazil, which was associated with a nosocomial hospital outbreak in Ribeirao Preto city.

Genomic deletions at 1p and 14q are associated with an abnormal cDNA microarray gene expression pattern in meningiomas but not in schwannomas

The molecular pathology of meningiomas and shwannomas involve the inactivation of the NF2 gene to generate grade I tumors. Genomic losses at 1p and 14q are observed in both neoplasms, although more frequently in meningiomas. The inactivation of unidentified genes located in these regions appears associated with tumor progression in meningiomas, but no clues to its molecular/clinical meaning are available in schwannomas. Recent microarray gene expression studies have demonstrated the existence of molecular subgroups in both entities. In the present study, we correlated the presence of genomic deletions at 1p, 14q, and 22q with the expression patterns of 96 tumor-related genes obtained by cDNA low-density microarrays in a series of 65 tumors including 42 meningiomas and 23 schwannomas. Two expression pattern groups were identified by cDNA mycroarray analysis when compared to the expression pattern in normal control RNA in both meningiomas and schwannomas, each one with patterns similar and different from the normal control. Meningioma and schwannoma subgroups differed in the expression of 38 and 16 genes, respectively. Using MLPA and microsatellites, we identified genomic losses at 1p, 14q, and 22q at nonrandom frequencies (12.5-69%) in meningiomas and schwannomas. Losses at 22q were almost equally frequent in both molecular expression subgroups in both neoplasms. However, deletions at 1p and 14q accumulated in meningiomas with a gene expression pattern different from the normal pattern, whereas the inverse situation occurred in schwannomas. Those anomalies characterized the schwannomas with expression pattern similar to the normal control. These findings suggest that deletions at 1p and 14q enhance the development of an abnormal tumor-related gene expression pattern in meningiomas, but this fact is not corroborated in schwannomas. (C) 2010 Elsevier Inc. All rights reserved.

Afro-Derived Brazilian Populations: Male Genetic Constitution Estimated by Y-Chromosomes STRs and AluYAP Element Polymorphisms

The genetic constitution of Afro-derived Brazilian populations is barely studied. To improve that knowledge, we investigated the AluYAP element and five Y-chromosome STRs (DYS19, DYS390, DYS391, DYS392, and DYS393) to estimate ethnic male contribution in the constitution of four Brazilian quilombos remnants: Mocambo, Rio das Ras, Kalunga, and Riacho de Sacutiaba. Results indicated significant differences among communities, corroborating historical information about the Brazilian settlement. We concluded that besides African contribution, there was a great European participation in the constitution of these four populations and that observed haplotype variability could be explained by gene flow to quilombos remnants and mutational events in microsatellites (STRs). Am. J. Hum. Biol. 21:354-356, 2009. (C) 2009 Wiley-Liss, Inc.

Allelic status of 1p and 19q in oligodendrogliomas and glioblastomas: multiplex ligation-dependent probe amplification versus loss of heterozygosity

Identification of the 1p/19q allelic status in gliomas, primarily those with a major oligodendroglial component, has become an excellent molecular complement to tumor histology in order to identify those cases sensitive to chemotherapy. In addition to loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), or comparative genomic hybridization (CGH), multiplex ligation-dependent probe amplification (MLPA) has been shown to be an alternative methodology to identify deletions of those chromosome arms. We used MLPA to explore the 1p and 19q glioblastomas, and a series of 76 gliomas: 41 tumors with a major oligodendroglial component, 34 glioblastomas, and one low-grade astrocytoma. We compared the MLPA findings of the oligodendroglial cases with those previously obtained using LOH in the same samples. Thirty-eight of 41 oligodendrogliomas displayed identical findings by both LOH and MLPA, and losses at either 1p and/or 19q were identified in 12 of 35 (34%) astrocytic tumors. These findings agree with data previously reported comparing MLPA versus FISH or CGH in gliomas and suggest that MLPA can be used in the identification 1p/19q allelic deletions on these brain neoplams. (c) 2009 Elsevier Inc. All rights reserved. reserved.

Meningiomas and schwannomas: Molecular subgroup classification found by expression arrays

Microarray gene expression profiling is a high-throughput system used to identify differentially expressed genes and regulation patterns, and to discover new tumor markers. As the molecular pathogenesis of meningiomas and schwannomas, characterized by NF2 gene alterations, remains unclear and suitable molecular targets need to be identified, we used low density cDNA microarrays to establish expression patterns of 96 cancer-related genes on 23 schwannomas, 42 meningiomas and 3 normal cerebral meninges. We also performed a mutational analysis of the NF2 gene (PCR, dHPLC, Sequencing and MLPA), a search for 22q LOH and an analysis of gene silencing by promoter hypermethylation (MS-MLPA). Results showed a high frequency of NF2 gene mutations (40%), increased 22q LOH as aggressiveness increased, frequent losses and gains by MLPA in benign meningiomas, and gene expression silencing by hypermethylation. Array analysis showed decreased expression of 7 genes in meningiomas. Unsupervised analyses identified 2 molecular subgroups for both meningiomas and schwannomas showing 38 and 20 differentially expressed genes, respectively, and 19 genes differentially expressed between the two tumor types. These findings provide a molecular subgroup classification for meningiomas and schwannomas with possible implications for clinical practice.

Who were the male founders of rural Brazilian Afro-derived communities? A proposal based on three populations

Background: Brazilian Quilombos are Afro-derived communities founded mainly by fugitive slaves between the 16(th) and 19(th) centuries; they can be recognized today by ancestral and cultural characteristics. Each of these remnant communities, however, has its own particular history, which includes the migration of non-African derived people. Methods: The present work presents a proposal for the origin of the male founder in Brazilian quilombos based on Y-haplogroup distribution. Y haplogroups, based on 16 binary markers (92R7, SRY2627, SRY4064, SRY10831.1 and .2, M2, M3, M09, M34, M60, M89, M213, M216, P2, P3 and YAP), were analysed for 98 DNA samples from genetically unrelated men from three rural Brazilian Afro-derived communities-Mocambo, Rio das Ras and Kalunga-in order to estimate male geographic origin. Results: Data indicated significant differences among these communities. A high frequency of non-African haplogroups was observed in all communities. Conclusions: This observation suggested an admixture process that has occurred over generations and directional mating between European males and African female slaves that must have occurred on farms before the slaves escaped. This means that the admixture occurred before the slaves escaped and the foundation of the quilombo.

Cigarette Smoking Exacerbates Nonalcoholic Fatty Liver Disease in Obese Rats

The prevalence of cigarette smoking (CS) is increased among obese subjects, who are susceptible to develop nonalcoholic fatty liver disease (NAFLD). We investigated the hepatic effects of CS in control and obese rats. Control and obese Zucker rats were divided into smokers and nonsmokers (n = 12 per group). Smoker rats were exposed to 2 cigarettes/day, 5 days/week for 4 weeks. The effects of CS were assessed by biochemical analysis, hepatic histological examination, immunohistochemistry, and gene expression analysis. Phosphorylation of AKT and extracellular signal-regulated kinase (ERK) and quantification of carbonylated proteins were assessed by western blotting. As expected, obese rats showed hypercholesterolemia, insulin resistance, and histological features of NAFLD. Smoking did not modify the lipidic or glucidic serum profiles. Smoking increased alanine aminotransferase serum levels and the degree of liver injury in obese rats, whereas it only induced minor changes in control rats. Importantly, CS increased the histological severity of NAFLD in obese rats. We also explored the potential mechanisms involved in the deleterious effects of CS. Smoking increased the degree of oxidative stress and hepatocellular apoptosis in obese rats, but not in controls. Similarly, smoking increased the hepatic expression of tissue inhibitor of metalloproteinase-1 and procollagen-alpha2(I) in obese rats, but not in controls. Finally, smoking regulated ERK and AKT phosphorylation. The deleterious effects of CS were not observed after a short exposure (5 days). Conclusion: CS causes oxidative stress and worsens the severity of NAFLD in obese rats. Further studies should assess whether this finding also occurs in patients with obesity and NAFLD. (HEPATOLOGY 2010;51:1567-1576.)

Historia Nova do Brasil: revisiting a polemical work

This article discusses the texts and purposes of the Historia Nova do Brasil series, a joint production of the Ministerio da Educacao e Cultura and the Instituto Superior de Estudos Brasileiros (Iseb) launched in 1964 and soon aborted by the military dictatorship. The intent is to reconstitute its context to present the many influences on this project and to examine its impact and the debates and disputes that resulted, to try to recover the details of this important effort at renewing the teaching of history in Brazil.

Reliability of short comparative genomic hybridization in fibroblasts and blastomeres for a comprehensive aneuploidy screening: first clinical application

BACKGROUND: Comparative genomic hybridization (CGH) is a valuable alternative to fluorescence in situ hybridization (FISH) for preimplantation genetic screening (PGS) because it allows full karyotype analysis. However, this approach requires the cryopreservation of biopsied embryos until results are available. The aim of this study is to reduce the hybridization period of CGH, in order to make this short-CGH technique suitable for PGS of Day-3 embryos, avoiding the cryopreservation step. METHODS: Thirty-two fibroblasts from six aneuploid cell lines (Coriell) and 48 blastomeres from 10 Day-4 embryos, discarded after PGS by FISH with 9 probes (9-chr-FISH), were analysed by short-CGH. A reanalysis by the standard 72 h-CGH and FISH using telomeric probes was performed when no concordant results between short-CGH and FISH diagnosis were observed. The short-CGH was subsequently applied in a clinical case of advanced maternal age. RESULTS: In 100% of the fibroblasts analysed, the characteristic aneuploidies of each cell line were detected by short-CGH. The results of the 48 blastomeres screened by short-CGH were supported by both 72 h-CGH results and FISH reanalysis. The chromosomes most frequently involved in aneuploidy were 22 and 16, but aneuploidies for the other chromosomes, excepting 1, 10 and 13, were also detected. Forty-one of the 94 aneuploid events observed (43.6%) corresponded to chromosomes which are not analysed by 9-chr-FISH. CONCLUSIONS: We have performed a preliminary validation of the short-CGH technique, including one clinical case, suggesting this approach may be applied to Day-3 aneuploidy analysis, thereby avoiding embryo cryopreservation and perhaps helping to improve implantation rate after PGS.

Como sonhar grande, mas n??o implementar tanto assim: Coordena????o de Desenvolvimento do Minist??rio do Trabalho da Jord??nia

O caso versa sobre a coopera????o entre o Canad?? e a Jord??nia no desenvolvimento de uma estrat??gia denominada ???Educa????o para o Emprego e Capacita????o T??cnica e Vocacional (E-TVET)???. Dentro do Minist??rio do Trabalho jordaniano, ??rg??o que liderava a a????o, foi criada uma unidade de coordena????o, para qual foi disponibilizada pela coopera????o canadense uma assessora com expertise em educa????o, Brenda Cooke. Sua tarefa era apoiar o estabelecimento e a operacionaliza????o dessa unidade, conforme termo de refer??ncia. Contando com a boa assist??ncia t??cnica da consultora, o projeto deu certo e gerou li????es importantes que s??o descritas no caso, como a administra????o adequada das expectativas dos atores envolvidos, abordagem participativa para estabelecer as regras de funcionamento da unidade etc. O caso presta-se ao ensino de temas como coopera????o internacional, lideran??a, gest??o de projetos e outros

Escuela nacional de administraci??n p??blica

La Escuela Nacional de Administraci??n P??blica - ENAP es una fundaci??n p??blica vinculada al Ministerio de Planificaci??n, Presupuesto y Gesti??n. Fundada en 1986, tiene como misi??n principal "desarrollar las competencias de funcionarios p??blicos, con el prop??sito de mejorar la capacidad gubernamental de administrar pol??ticas p??blicas". Para cumplir con su misi??n ofrece un amplio programa de ense??anza y educaci??n continua a los gestores de pol??ticas p??blicas, adem??s del E-Learning (cursos online) y cursos personlizados de acuerdo con los objetivos institucionales y gubernamentales. Los cursos de la ENAP son planeados de acuerdo con las demandas estrat??gicas gubernamentales de inclusi??n social, reducci??n de la pobreza, y desarrollo econ??mico para fortalecer el liderazgo de la democracia sudamericana. El alcance y la diversidad de sus programas reflejan los desaf??os de los grandes cambios en el mercado y ambiente de trabajo, lo que es enfrentado por los actuales 550.000 funcionarios p??blicos y m??s de 7.000.000 funcionarios p??blicos estatales y municipales que hay en Brasil, de acuerdo con el ??ltimo conteo en 2006.

Sa??de materno infantil no Brasil: evolu????o e programas desenvolvidos pelo Minist??rio da Sa??de

Trata-se de uma revis??o de literatura com o objetivo de descrever a evolu????o da aten????o ?? sa??de materno infantil no Brasil desde o Estado Novo at?? os dias atuais. O levantamento de dados foi realizado em livros, sites do Minist??rio da Sa??de, Legisla????es do Di??rio Oficial e artigos das bases de dados Biblioteca Virtual em Sa??de (BVS/Bireme), Medline e Scientific Eletronic Library (Scielo). As pol??ticas p??blicas de sa??de materno infantil foram definidas seguindo desde os princ??pios meramente reprodutivos at?? aqueles mais amplos, voltados para garantir uma melhor condi????o de sa??de e de vida. Nas ??ltimas d??cadas, com o aux??lio do governo e da sociedade, houve uma progress??o no atendimento da sa??de da mulher e da crian??a. No entanto, conclui-se que, apesar da evolu????o observada, o grande desafio ainda se encontra na redu????o da morbimortalidade materna, neonatal e infantil.

Avalia????o de pol??ticas de financiamento a micro e pequenas empresas na gera????o de postos de trabalho: o caso do Proger ??? principais aspectos

O artigo se prop??e a apresentar os principais aspectos e resultados de uma nova metodologia de avalia????o de programas de financiamento a micro e pequenas empresas aplicada ao Programa de Gera????o de Emprego e Renda na ??rea urbana ??? Proger urbano, tanto no que se refere aos seus custos efetivos, at?? ent??o desconhecidos, quanto no que se refere ao seu impacto sobre a gera????o de empregos, estimado utilizando dados prim??rios oriundos do cruzamento de dois bancos de dados do Minist??rio do Trabalho e Emprego, quais sejam, o do Sistema de Acompanhamento da Execu????o do Proger (Saep), e o do Cadastro Geral de Empregados e Desempregados. S??o apresentados, preliminarmente, alguns dos resultados de duas avalia????es anteriores do programa, uma realizada pelo Ibase, atrav??s de question??rios aos benefici??rios do programa, e outra, uma primeira experi??ncia de cruzamento dos dois referidos bancos de dados, que serviu de base para a avalia????o que se apresenta.

Desenvolvimento sustent??vel: o desafio da admininstra????o p??blica brasileira nas dimens??es da relev??ncia social, da prud??ncia ecol??gica e da viabilidade econ??mica

Partindo do conceito de bem-estar social, definido em lei como de responsabilidade da administra????o p??blica, especialmente no que diz respeito ?? preserva????o dos recursos naturais para a manuten????o da decente qualidade de vida dos cidad??os, o artigo foi estruturado a partir do relat??rio de pesquisa de inicia????o cient??fica financiada pela Funda????o de Amparo ?? Pesquisa do Estado de S??o Paulo (Fapesp) e desenvolvido na Universidade Estadual de S??o Paulo (Unesp). Tal relat??rio objetivou investigar os par??metros de regularidade da administra????o p??blica, analisando-se a jurisprud??ncia dos tribunais. Foram evidenciadas irregularidades na atua????o da administra????o p??blica, constatando a desarticula????o da gest??o p??blica ao gerir as tr??s dimens??es que definem o desenvolvimento sustent??vel: a relev??ncia social, a viabilidade econ??mica e a prud??ncia ecol??gica. Foi poss??vel constatar com esta pesquisa que a administra????o p??blica brasileira d?? mais import??ncia para a quest??o econ??mica que ??s quest??es sociais e ambientais. Pudemos perceber que enquanto o meio ambiente ?? degradado e a sociedade prejudicada com a piora da qualidade de vida, o econ??mico vem sendo privilegiado constantemente. Sendo assim, evidenciaremos esse descaso propondo algumas mudan??as para a melhora da gest??o das tr??s dimens??es do desenvolvimento sustent??vel; por??m, em contrapartida, mostraremos a seriedade na atua????o dos ??rg??os colegiados ambientais e institui????es do poder p??blico, tais como o Minist??rio P??blico, que hoje atuam em parceria com a popula????o, crescentemente envolvida no processo mediante a pr??tica de den??ncias e reclama????es.