Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

Fatores associados ao acesso geográfico aos serviços de saúde por pessoas com tuberculose em três capitais do Nordeste brasileiro

O objetivo do presente estudo foi identificar fatores associados ao acesso geográfico aos serviços de saúde por portadores de tuberculose em três capitais do Nordeste do Brasil. A amostra foi composta por casos novos de tuberculose, notificados em 2007. Foram utilizados dados provenientes do Sistema de Informação sobre Agravos de Notificação, e do Cadastro Nacional de Estabelecimento de Saúde. Os endereços dos domicílios e das unidades de saúde foram georreferenciados e, utilizando a distância entre o domicílio e a unidade de atendimento de cada caso, foi considerado acesso dificultado quando esta distância foi maior do que 800 metros. Foram estimadas as razões de prevalência bruta e ajustada por meio de regressão de Poisson. Verificou-se que após ajuste com as variáveis estudadas, apenas a variável unidade básica, em Salvador, Bahia (RP = 0,75; IC95%: 0,720-0,794) e em Recife, Pernambuco (RP = 0,402; IC95%: 0,318-0,508), manteve associação com o acesso dificultado. O estudo concluiu que a descentralização do atendimento em unidade básica pode contribuir com a melhoria do acesso aos serviços de saúde.</p

Óbitos e internações por tuberculose não notificados no município do Rio de Janeiro

OBJETIVO: Analisar a subnotificação de óbitos e internações por tuberculose no Sistema de Informação de Agravos de Notificação (Sinan). MÉTODOS: Foram selecionados os óbitos do Sistema de Informação sobre Mortalidade (SIM) com tuberculose como causa básica ou associada e as internações do Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS) com causa principal ou secundária tuberculose de residentes no município do Rio de Janeiro em 2004. Foi realizada associação probabilística das bases de dados do SIM e SIH-SUS com a do Sinan, referentes aos anos de 2002 a 2004. RESULTADOS: Dos 542 óbitos por tuberculose no período, 234 (43,2%) não foram registrados no Sinan nos dois anos anteriores. Das 1.079 internações, 238 (22,1%) não foram notificadas. Foram relacionados às internações 71 óbitos: 47 ocorreram durante a internação por tuberculose, 24 após a internação. Sete não foram notificados no Sinan. Os idosos tiveram 1,6 vez (IC95% 1,074;2,516) a chance de não notificação dos mais jovens, e pessoas com nível superior ou mais escolaridade tiveram 3,6 vezes a chance (IC95% 1,384;11,022) daqueles com nenhum ano de estudo de não serem notificadas. Os menores de 15 anos tiveram 4,8 vezes a chance (IC95% 2,757;8,452) de não notificação daqueles entre 15 e 59 anos. Algumas divisões regionais de saúde apresentaram percentual de óbitos não notificados acima de 50% e esse percentual variou entre 37,8% e 12,7% para internações. CONCLUSÕES: Os dados sugerem problemas na detecção de casos e apontam barreiras de acesso ao tratamento oportuno e adequado e falhas na qualidade do sistema de informação, com diferenças entre as regiões do município.OBJETIVO: Analizar la subnotificación de óbitos e internaciones por tuberculosis en el Sistema de Información de Agravios de Notificación (Sinan). MÉTODOS: Se seleccionaron los óbitos del Sistema de Información sobre Mortalidad (SIM) con causa básica o asociada a tuberculosis y las internaciones del Sistema de Informaciones Hospitalarias del Sistema Único de Salud con causa principal o secundaria tuberculosis de residentes en el municipio de Rio de Janeiro (Sureste de Brasil) en 2004. Se realizó asociación probabilística de las bases de datos del SIM y SIH-SUS con la del Sinan, referentes a los años de 2002 a 2004. RESULTADOS: De los 542 óbitos por tuberculosis en el período, 234 (43,2%) no fueron registrados en el Sinan en los dos años anteriores. De las 1.079 internaciones, 238 (22,1%) no fueron notificadas. Se relacionaron a las internaciones 71 óbitos: 47 durante la internación por tuberculosis, 24 posterior a la internación. Siete no fueron notificados en el Sinan. Los ancianos presentaron 1,6 veces (IC 95% 1,074;2,516) la probabilidad de no notificación con relación a los más jóvenes, y personas con nivel superior o más de escolaridad presentaron 3,6 veces la probabilidad (IC 95% 1,384;11,022) de no ser notificados con relación a los que no tenían ningún año de estudio. Los menores de 15 años reflejaron 4,8 veces la probabilidad (IC 95% 2,757;8,452) de no notificación con respecto a los que tenían de 15 a 59 años. Algunas divisiones regionales de salud presentaron porcentaje de óbitos no notificados por encima del 50% y ese porcentaje varió entre 37,8% a 12,7% para internaciones. CONCLUSIONES: Los datos sugieren problemas en la detección de casos y apuntan barreras de acceso al tratamiento oportuno y adecuado y fallas en la calidad del sistema de información, con diferencias entre las regiones del municipio.OBJECTIVE: To analyze underreporting of deaths and hospital admissions from tuberculosis to the Information System for Notifiable Diseases (SINAN). METHODS: Cases with tuberculosis as basic or associated cause of death were selected from the Brazilian Mortality Information System (SIM) and hospital admissions for tuberculosis as main or secondary cause from the Hospital Information System of the Brazilian Unified Health System (SIH-SUS), for residents in the municipality of Rio de Janeiro in 2004. Probabilistic record linkage was carried out between the SIM and SIH-SUS databases and the SINAN for the years 2002 to 2004. RESULTS: Out of the 542 deaths from tuberculosis in the period, 234 (43.2%) were not registered in the SINAN for the two previous years. As for the 1,079 admissions, 238 (22.1%) failed to be notified. Seventy-one deaths were related to these admissions: 47 were registered out of the SIH-SUS by death, 24 occurred after discharge and seven remained unnotified in the SINAN. The elderly were 1.6 times (95%CI 1.074;2.516) less likely to be notified than younger patients, and those with at least a college education were 3.6 times (95%CI 1.384;11.022) less likely to be notified than those with no formal education. Patients under 15 were 4.8 times (95%CI 2.757;8.452) less likely to be notified than those aged between 15 and 59 years. Some regional health administration divisions showed a percentage of unnotified deaths of over 50% and this percentage ranged from 37.8% to 12.7% for hospital admissions. CONCLUSIONS: The data suggest problems in the detection of cases and point to obstacles in adequate and timely treatment, as well as to quality flaws in the information system, with differences among regions in the municipality

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Direct Bacterial Killing In Vitro by Recombinant Nod2 Is Compromised by Crohn's Disease-Associated Mutations

Background: A homeostatic relationship with the intestinal microflora is increasingly appreciated as essential for human health and wellbeing. Mutations in the leucine-rich repeat (LRR) domain of Nod2, a bacterial recognition protein, are associated with development of the inflammatory bowel disorder, Crohn’s disease. We investigated the molecular mechanisms underlying disruption of intestinal symbiosis in patients carrying Nod2 mutations. Methodology/Principal Findings: In this study, using purified recombinant LRR domains, we demonstrate that Nod2 is a direct antimicrobial agent and this activity is generally deficient in proteins carrying Crohn’s-associated mutations. Wildtype, but not Crohn’s-associated, Nod2 LRR domains directly interacted with bacteria in vitro, altered their metabolism and disrupted the integrity of the plasma membrane. Antibiotic activity was also expressed by the LRR domains of Nod1 and other pattern recognition receptors suggesting that the LRR domain is a conserved anti-microbial motif supporting innate cellular immunity. Conclusions/Significance: The lack of anti-bacterial activity demonstrated with Crohn’s-associated Nod2 mutations in vitro, supports the hypothesis that a deficiency in direct bacterial killing contributes to the association of Nod2 polymorphism

Underlying Factors Associated with Anemia in Amazonian Children: A Population-Based, Cross-Sectional Study

Background: Although iron deficiency is considered to be the main cause of anemia in children worldwide, other contributors to childhood anemia remain little studied in developing countries. We estimated the relative contributions of different factors to anemia in a population-based, cross-sectional survey. Methodology: We obtained venous blood samples from 1111 children aged 6 months to 10 years living in the frontier town of Acrelandia, northwest Brazil, to estimate the prevalence of anemia and iron deficiency by measuring hemoglobin, erythrocyte indices, ferritin, soluble transferrin receptor, and C-reactive protein concentrations. Children were simultaneously screened for vitamin A, vitamin B-12, and folate deficiencies; intestinal parasite infections; glucose-6-phosphate dehydrogenase deficiency; and sickle cell trait carriage. Multiple Poisson regression and adjusted prevalence ratios (aPR) were used to describe associations between anemia and the independent variables. Principal Findings: The prevalence of anemia, iron deficiency, and iron-deficiency anemia were 13.6%, 45.4%, and 10.3%, respectively. Children whose families were in the highest income quartile, compared with the lowest, had a lower risk of anemia (aPR, 0.60; 95% CI, 0.37-0.98). Child age (&lt;24 months, 2.90; 2.01-4.20) and maternal parity (&gt;2 pregnancies, 2.01; 1.40-2.87) were positively associated with anemia. Other associated correlates were iron deficiency (2.1; 1.4-3.0), vitamin B-12 (1.4; 1.0-2.2), and folate (2.0; 1.3-3.1) deficiencies, and C-reactive protein concentrations (&gt;5 mg/L, 1.5; 1.1-2.2). Conclusions: Addressing morbidities and multiple nutritional deficiencies in children and mothers and improving the purchasing power of poorer families are potentially important interventions to reduce the burden of anemia.Sao Paulo State Research Agency [FAPESP 07/53042-1]Sao Paulo State Research AgencyNational Research Agency of BrazilNational Research Agency of Brazil [CNPq 470573/2007-4