Diversity in Paracoccidioides brasiliensis. the PbGP43 gene as a genetic marker

Paracoccidioides brasiliensis is a temperature-dependent dimorphic fungus and the agent of paracoccidioidomycosis (PCM), which is prevalent in rural workers of Latin American countries. Until a decade ago, most of the studies involving P. brasiliensis used clinical isolates, since environmental samples from soil are difficult to obtain. More recently, P. brasiliensis has been isolated from infected wild and domestic animals, especially from the nine-banded armadillo Dasypus novemcinctus in Brazil. Over the years, diversity within the species has been observed at several phenotypic levels. the present review will discuss the reports focusing on genetic polymorphism, which culminated with the detection of P. brasiliensis phylogenetic species as a result of a multilocus study. Polymorphism in the PbGP43 gene is detailed. This gene encodes fungal glycoprotein gp43, a dominant P. brasiliensis antigen largely studied in the last two decades for its importance in diagnosis, immune protection, and adhesive properties to extracellular matrix-associated proteins. Fungal traits associated with genetic groups are discussed.Universidade Federal de São Paulo, Div Cell Biol, BR-04023062 São Paulo, BrazilCIB, Medellin, ColombiaUniv Antioquia, Medellin, ColombiaUniv Fed Minas Gerais, Div Microbiol, Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Div Cell Biol, BR-04023062 São Paulo, BrazilWeb of Scienc

HIERARQUIA URBANA E CRIAÇÃO DE MUNICÍPIOS: ANÁLISE ESPACIAL DOS IMPACTOS DA CRIAÇÃO DE MUNICÍPIOS NOS POLOS REGIONAIS NOS PERÍODOS DEMOCRÁTICOS DE 1946-1964 E PÓS-1988

O processo de criação de municípios no Brasil está intimamente ligado aos ciclos políticos de centralização e descentralização do poder no século XX. Os períodos de regimes formalmente democráticos de 1946 e 1964 e pÛs-1988 com a redemocratização foram os períodos mais intensos da história brasileira de criação de municípios. Nesses períodos foram criados cerca de 70% dos municípios hoje existentes. Esse processo resulta em grandes distorções espaciais na transferência de repasses federais entre estados e regiões do Brasil favorecendo as regiões que concentraram a criação de novas unidades em ambos os períodos. Além disso, como o número de novas unidades municipais criadas tinham pequena população e ao mesmo tempo oferta restrita de comércio e sérvios, já que desempenhariam as funções mais baixas da hierarquia urbana a criação massiva de novas unidades também traria impactos profundos sobre os polos urbanos de destaque nas regiões de concentração de novos municípios. A criação de um grande número de novos municípios na área de influência dos polos resultaria no aumento da renda da área de mercado do polo, que se traduziria em aumento na demanda de comércio e serviços dos polos que mais receberam novos municípios pequenos no seu entorn

MORTALIDADE POR CAUSAS GARBAGE NOS MUNICÍPIOS BRASILEIROS: DIFERENÇAS ENTRE AS ESTIMATIVAS DIRETAS E INDIRETAS EM 2015 A 2017

Objectives: the present study aims to generate estimates of mortality rates due to garbage codes (GC) for municipalities in Brazil by comparing direct and indirect methods, based on deaths registered in the Mortality Information System (SIM) between 2015 and 2017. Methods: Data from the SIM were used. The analysis was performed in groups of GC, levels 1 and 2, levels 3 and 4 and total GC. Mortality rates were estimated directly and indirectly, Empirical Bayesian Estimators. Results: about 38% of CG were estimated and regional differences in mortality rates were observed, higher in the Northeast and Southeast and lower in the South and Midwest. The Southeast presented similar rates for the two groups of CG analyzed. The smallest differences between direct and indirect estimates were observed in large cities, above 500 thousand. The municipalities in the north of Minas Gerais and the states of Rio de Janeiro, São Paulo and Bahia presented municipalities with high rates at levels 1 and 2. Conclusion: there are differences in the quality of the definition of the underlying causes of death, even with the use of indirect methodology which assists in smoothing rates. The quality of the definition of causes of death is important since they are associated with the access and quality of health services and offer subsidies for health planning.Objetivos: o presente estudo tem como objetivo gerar estimativas das taxas de mortalidade por causas garbage (CG) para os municípios do Brasil fazendo a comparação entre métodos diretos e indiretos, tendo como base os óbitos registrados no SIM entre 2015 e 2017. Métodos: Os dados do Sistema de Informações sobre Mortalidade (SIM) foram utilizados. A análise foi realizada com grupos de GC, níveis 1 e 2, níveis 3 e 4 e total de GC. As taxas de mortalidade foram estimadas de forma direta e indireta, estimadores bayesianos empíricos. Resultados: observou-se cerca de 38% de CG e diferenças regionais nas taxas de mortalidade, maiores no Nordeste e Sudeste e menores no Sul e Centro-Oeste. O Sudeste apresentou taxas semelhantes para os dois grupos de CG analisados. As menores diferenças entre as estimativas diretas e indiretas foram observadas nas grandes cidades, acima de 500 mil. Os municípios do norte de Minas Gerais e estados do Rio de Janeiro, São Paulo e Bahia apresentaram municípios com altas taxas nos níveis 1 e 2. Conclusão: existem diferenças na qualidade da definição das causas básicas de morte, mesmo com o uso de metodologia indireta que auxilia na suavização das taxas. A qualidade da definição das causas de morte é importante, uma vez que se mostram associadas com o acesso e qualidade dos serviços de saúde e oferecem subsídios para o planejamento em saúde

Antifungal activity of schinol and a new biphenyl compound isolated from Schinus terebinthifolius against the pathogenic fungus Paracoccidioides brasiliensis

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to isolate and identify the antifungal compounds from the extracts of <it>Schinus terebinthifolius </it>(Anacardiaceae) against clinical isolates of the pathogenic fungus <it>Paracoccidioides brasiliensis</it>.</p> <p>Methods</p> <p>The hexane and dichlomethane fractions from leaves and stems of <it>S. terebinthifolius </it>were fractionated using several chromatography techniques to afford four compounds.</p> <p>Results</p> <p>The compounds isolated from <it>S. terebinthifolius </it>were identified as schinol (<b>1</b>), a new biphenyl compound, namely, 4'-ethyl-4-methyl-2,2',6,6'-tetrahydroxy[1,1'-biphenyl]-4,4'-dicarboxylate (<b>2</b>), quercetin (<b>3</b>), and kaempferol (<b>4</b>). Compounds <b>1 </b>and <b>2 </b>were active against different strains of <it>P. brasiliensis</it>, showing a minimal inhibitory concentration value against the isolate Pb B339 of 15.6 μg/ml. The isolate Pb 1578 was more sensitive to compound <b>1 </b>with a MIC value of 7.5 μg/ml. Schinol presented synergistic effect only when combined with itraconazole. The compounds isolated from S. <it>terebinthifolius </it>were not able to inhibit cell wall synthesis or assembly using the sorbitol assay.</p> <p>Conclusion</p> <p>This work reveals for the first time the occurrence of compound <b>2 </b>and discloses activity of compounds <b>1 </b>and <b>2 </b>against several clinical isolates of <it>P. brasiliensi</it>s. These results justify further studies to clarify the mechanisms of action of these compounds.</p

Beneficial effects of the activation of the Angiotensin-(1-7) MAS receptor in a murine model of adriamycin-induced nephropathy

Angiotensin-(1-7) [Ang-(1-7)] is a biologically active heptapeptide that may counterbalance the physiological actions of angiotensin II (Ang II) within the renin-angiotensin system (RAS). Here, we evaluated whether activation of the Mas receptor with the oral agonist, AVE 0991, would have renoprotective effects in a model of adriamycin (ADR)-induced nephropathy. We also evaluated whether the Mas receptor contributed for the protective effects of treatment with AT1 receptor blockers. ADR (10 mg/kg) induced significant renal injury and dysfunction that was maximal at day 14 after injection. Treatment with the Mas receptor agonist AVE 0991 improved renal function parameters, reduced urinary protein loss and attenuated histological changes. Renoprotection was associated with reduction in urinary levels of TGF-{beta}. Similar renoprotection was observed after treatment with the AT1 receptor antagonist, Losartan. AT1 and Mas receptor mRNA levels dropped after ADR administration and treatment with losartan reestablished the expression of Mas receptor and increased the expression of ACE2. ADR-induced nephropathy was similar in wild type (Mas(+/+)) and Mas knockout (Mas (-/-)) mice, suggesting there was no endogenous role for Mas receptor activation. However, treatment with Losartan was able to reduce renal injury only in Mas(+/+) , but not in Mas (-/-) mice. Therefore, these findings suggest that exogenous activation of the Mas receptor protects from ADR-induced nephropathy and contributes to the beneficial effects of AT1 receptor blockade. Medications which target specifically the ACE2/Ang-(1-7)/Mas axis may offer new therapeutic opportunities to treat human nephropathies

A relação entre PIB per capita e os acidentes de transporte nos municípios brasileiros, 2005, 2010 e 2015

Objective: The main objective of this paper is to analyze the relationship between GDP and three variables related to traffic accidents in Brazilian municipalities: traffic accident mortality, deaths per vehicle; and vehicles per inhabitant. Methods: 2005, 2010 and 2015 terrestrial traffic accident (ATT) mortality rates were estimated using a three years moving average and were standardized, then, we applied the empirical Bayes estimator (EBE). Fatality rates (deaths per vehicle) also were based on EBE. Vehicles per inhabitant considered the ratio between vehicle fleet and the population at municipal level. For every studied year, we estimated linear regression models between GDP and the interest variables. &nbsp;Results: Variables distribution indicates that, between 2005 and 2015, GDP and vehicles per inhabitant kept the same rising relationship. Fatality rates show a decreasing association with GDP. TA mortality distribution with GDP presented a pattern close to an inverted-U. Model coefficients practically did not change for the vehicle per inhabitant. Estimated association between deaths per vehicle and GDP kept the same sign, but diminished between 2005 and 2015. Model coefficient sign changed in 2015 for TA mortality. Conclusion: Similarly to what was observed in developed countries, the relationship between mortality from traffic accidents and GDP changed in the analyzed period.Objetivo: O artigo pretende analisar a relação entre o PIB per capita e três variáveis relacionadas aos acidentes de transporte nos municípios brasileiros: a mortalidade por acidentes de transporte terrestre (ATT); as mortes por veículo; e o número de veículos por pessoa. &nbsp;Métodos: As taxas de mortalidade por ATT foram estimadas (2005, 2010 e 2015) por meio do estimador bayesiano empírico (EBE). A taxa de mortalidade por veículo foi também estimada pelo EBE. O número de veículos por pessoa foi baseado na razão entre a frota de automóveis e a população residente. &nbsp;Para os três anos em análise, estimamos um modelo de regressão linear entre o PIB per capita municipal e as três variáveis de interesse.&nbsp; Resultados: A distribuição das variáveis mostra que a relação entre o PIB e número de veículos por pessoa se manteve crescente ao longo dos anos, e foi sempre negativa considerando&nbsp; as mortes por veículo. A taxa mortalidade por ATT apresentou distribuição próxima a um U-invertido.&nbsp; Os coeficientes do modelo de regressão praticamente não variaram para a relação entre PIB e os veículos por habitante. O sinal para o modelo com a taxa de mortalidade por veículo se manteve o mesmo (negativo), mas apresentou diminuição. A taxa mortalidade por ATT, por sua vez, apresentou inversão do sinal em 2015. &nbsp;Conclusões: De modo similar ao observado nos países desenvolvidos, parece ter havido uma inversão na relação entre mortalidade por ATT e PIB nos municípios brasileiros entre 2005 e 2015

Prediabetes and intermediate hyperglycemia prevalence in adults and associated factors, Health National Survey

O objetivo deste estudo foi avaliar a prevalência de pré-diabetes e hiperglicemia intermediária em adultos brasileiros, considerando diferentes critérios diagnósticos, e estabelecer fatores associados à sua ocorrência. Análise dos dados laboratoriais da Pesquisa Nacional de Saúde, coletados em 2014 e 2015. Foram calculadas as prevalências das condições conforme critérios da Associação Americana de Diabetes (ADA) – Hemoglobina Glicada (HbA1c) 5,7 a 6,4% – e da Organização Mundial de Saúde (OMS), de 6 – 6,4% entre aqueles que não tinham critério para diabetes. Razões de prevalência (RP) brutas e ajustadas e IC 95% foram calculados por regressão de Poisson com variância robusta. A prevalência de pré-diabetes pelo critério ADA foi de 18,5% e de 7,5% pelo critério da OMS. Verificou-se um gradiente de aumento das prevalências segundo a idade da população e presença de fatores de risco como hipertensão arterial, obesidade, circunferência abdominal elevada e baixo colesterol HDL. Os menos escolarizados e os declarados pretos apresentaram prevalências superiores. Este estudo aponta um intervalo entre 7,5 a 18,5% de adultos brasileiros que apresentam pré-diabetes e hiperglicemia intermediária, além de identificar um escore de risco para a ocorrência dessa condição.This study aimed to evaluate the prevalence of prediabetes and intermediate hyperglycemia in Brazilian adults, according to different diagnostic criteria, and establish associated factors to its occurrence. We analyzed the National Health Survey laboratory data collected from 2014 to 2015. The prevalence of the conditions was calculated according to the American Diabetes Association (ADA) diagnostic criteria based on glycated hemoglobin (HbA1c) 5.7%-6.4%, and the World Health Organization (WHO) 6-6.4%, among those without criteria for diabetes. Crude and adjusted prevalence rates (PR) and 95% CI were calculated using Poisson regression with robust variance. The prevalence of prediabetes by ADA and WHO criteria was 18.5 and 7.5%, respectively. We observed a gradient of increased prevalence by the age of the population and risk factors, like arterial hypertension, obesity, elevated waist circumference, and low HDL cholesterol levels. Less educated people and the self-declared black had a higher prevalence. This study pointed out a range from 7.5 to 18.5% of Brazilian adults with prediabetes and intermediate hyperglycemia and identified a risk score to this condition’s occurrence

Identification and characterization of Tc1/mariner-like DNA transposons in genomes of the pathogenic fungi of the Paracoccidioides species complex

<p>Abstract</p> <p>Background</p> <p><it>Paracoccidioides brasiliensis </it>(Eukaryota, Fungi, Ascomycota) is a thermodimorphic fungus, the etiological agent of paracoccidioidomycosis, the most important systemic mycoses in Latin America. Three isolates corresponding to distinct phylogenetic lineages of the <it>Paracoccidioides </it>species complex had their genomes sequenced. In this study the identification and characterization of class II transposable elements in the genomes of these fungi was carried out.</p> <p>Results</p> <p>A genomic survey for DNA transposons in the sequence assemblies of <it>Paracoccidioides</it>, a genus recently proposed to encompass species <it>P. brasiliensis </it>(harboring phylogenetic lineages S1, PS2, PS3) and <it>P. lutzii </it>(<it>Pb01-like </it>isolates), has been completed. Eight new <it>Tc1/mariner </it>families, referred to as Trem (<b>Tr</b>ansposable <b>e</b>lement <b>m</b>ariner), labeled A through H were identified. Elements from each family have 65-80% sequence similarity with other <it>Tc1/mariner </it>elements. They are flanked by 2-bp TA target site duplications and different termini. Encoded DDD-transposases, some of which have complete ORFs, indicated that they could be functionally active. The distribution of Trem elements varied between the genomic sequences characterized as belonging to <it>P. brasiliensis </it>(S1 and PS2) and <it>P. lutzii</it>. TremC and H elements would have been present in a hypothetical ancestor common to <it>P. brasiliensis </it>and <it>P. lutzii</it>, while TremA, B and F elements were either acquired by <it>P. brasiliensis </it>or lost by <it>P. lutzii </it>after speciation. Although TremD and TremE share about 70% similarity, they are specific to <it>P. brasiliensis </it>and <it>P. lutzii</it>, respectively. This suggests that these elements could either have been present in a hypothetical common ancestor and have evolved divergently after the split between <it>P. brasiliensis </it>and <it>P. Lutzii</it>, or have been independently acquired by horizontal transfer.</p> <p>Conclusions</p> <p>New families of <it>Tc1/mariner </it>DNA transposons in the genomic assemblies of the <it>Paracoccidioides </it>species complex are described. Families were distinguished based on significant BLAST identities between transposases and/or TIRs. The expansion of Trem in a putative ancestor common to the species <it>P. brasiliensis </it>and <it>P. lutzii </it>would have given origin to TremC and TremH, while other elements could have been acquired or lost after speciation had occurred. The results may contribute to our understanding of the organization and architecture of genomes in the genus <it>Paracoccidioides</it>.</p

Susceptibilidade a antimicrobianos de cocos Gram-positivos anaeróbios estritos isolados em primatas Calitriquídeos (Callithrix penicillata e Callithrix jacchus)

The purpose of this study was to evaluate the susceptibility profile to antimicrobial drugs of the anaerobic Gram-positive cocci from the oral cavity and fecal specimens of marmosets (Callithrix penicillata and Callithrix jacchus) maintained in captivity. The samples isolated from fecal specimens were found to be sensitive to penicillin G, cephalothin, cefotaxime, ampicillin and chloramphenicol as well as they showed resistance to clindamycin, cefoxitin, erythromycin, tetracycline, imipenem and metronidazole. The isolated oral samples were sensitive to penicillin G, cephalotin, cefoxitin, cefotaxime and chloramphenicol, but resistant to clindamycin, ampicillin, metronidazole, erythromycin, tetracycline and imipenem. The susceptibility profile to antimicrobial drugs of intestinal and oral Gram positive cocci of C. penicillata and C. jacchus showed the existence of multi-resistance in some strains, up to 5 drugs.O objetivo do presente trabalho foi identificar o perfil de susceptibilidade a drogas antimicrobianas de cocos Grampositivos anaeróbios estritos isolados da cavidade oral e em espécimes fecais de sagüis Calitriquídeos (C. penicillata e C. jacchus) mantidos em cativeiro. As cepas isoladas de espécimes fecais foram sensíveis a penicilina G, cefalotina, cefotaxima, ampicilina e cloranfenicol e resistentes a clindamicina, cefoxitina, eritromicina, tetraciclina, imipenem e metronidazol. Os isolados orais apresentaram sensibilidade a penicilina G, cefalotina, cefoxitina, cefotaxima e cloranfenicol e resistência a clindamicina, ampicilina, metronidazol, eritromicina, tetraciclina e imipenem. O perfil de susceptibilidade a antimicrobianos de cocos Gram-positivos anaeróbios estritos intestinais e orais isolados em Calitriquídeos mostrou a ocorrência de multirresistência, em algumas cepas, até a cinco drogas

IFN-γ Production Depends on IL-12 and IL-18 Combined Action and Mediates Host Resistance to Dengue Virus Infection in a Nitric Oxide-Dependent Manner

Dengue is a mosquito-borne disease caused by one of four serotypes of Dengue virus (DENV-1–4). Severe dengue infection in humans is characterized by thrombocytopenia, increased vascular permeability, hemorrhage and shock. However, there is little information about host response to DENV infection. Here, mechanisms accounting for IFN-γ production and effector function during dengue disease were investigated in a murine model of DENV-2 infection. IFN-γ expression was greatly increased after infection of mice and its production was preceded by increase in IL-12 and IL-18 levels. In IFN-γ−/− mice, DENV-2-associated lethality, viral loads, thrombocytopenia, hemoconcentration, and liver injury were enhanced, when compared with wild type-infected mice. IL-12p40−/− and IL-18−/− infected-mice showed decreased IFN-γ production, which was accompanied by increased disease severity, higher viral loads and enhanced lethality. Blockade of IL-18 in infected IL-12p40−/− mice resulted in complete inhibition of IFN-γ production, greater DENV-2 replication, and enhanced disease manifestation, resembling the response seen in DENV-2-infected IFN-γ−/− mice. Reduced IFN-γ production was associated with diminished Nitric Oxide-synthase 2 (NOS2) expression and NOS2−/− mice had elevated lethality, more severe disease evolution and increased viral load after DENV-2 infection. Therefore, IL-12/IL-18-induced IFN-γ production and consequent NOS2 induction are of major importance to host resistance against DENV infection