Impaired Innate Immunity in Tlr4−/− Mice but Preserved CD8+ T Cell Responses against Trypanosoma cruzi in Tlr4-, Tlr2-, Tlr9- or Myd88-Deficient Mice

The murine model of T. cruzi infection has provided compelling evidence that development of host resistance against intracellular protozoans critically depends on the activation of members of the Toll-like receptor (TLR) family via the MyD88 adaptor molecule. However, the possibility that TLR/MyD88 signaling pathways also control the induction of immunoprotective CD8+ T cell-mediated effector functions has not been investigated to date. We addressed this question by measuring the frequencies of IFN-γ secreting CD8+ T cells specific for H-2Kb-restricted immunodominant peptides as well as the in vivo Ag-specific cytotoxic response in infected animals that are deficient either in TLR2, TLR4, TLR9 or MyD88 signaling pathways. Strikingly, we found that T. cruzi-infected Tlr2−/−, Tlr4−/−, Tlr9−/− or Myd88−/− mice generated both specific cytotoxic responses and IFN-γ secreting CD8+ T cells at levels comparable to WT mice, although the frequency of IFN-γ+CD4+ cells was diminished in infected Myd88−/− mice. We also analyzed the efficiency of TLR4-driven immune responses against T. cruzi using TLR4-deficient mice on the C57BL genetic background (B6 and B10). Our studies demonstrated that TLR4 signaling is required for optimal production of IFN-γ, TNF-α and nitric oxide (NO) in the spleen of infected animals and, as a consequence, Tlr4−/− mice display higher parasitemia levels. Collectively, our results indicate that TLR4, as well as previously shown for TLR2, TLR9 and MyD88, contributes to the innate immune response and, consequently, resistance in the acute phase of infection, although each of these pathways is not individually essential for the generation of class I-restricted responses against T. cruzi

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Fatores associados ao consumo precoce de leite de vaca integral por crianças menores de um ano de idade

Objective: To assess the frequency and factors associated with the use of whole cow’s milk in children under one year old in the city of Fortaleza, Ceará. Methods: Cross-sectional analytical study conducted with 575 mothers of children under one year old living in the city of Fortaleza, Ceará. A semi-structured questionnaire was applied to collect sociodemographic data and information about the reproductive history of mothers, childbirth and the child. Results: The median age of mothers was 26.5 years, and 80.5% (n=463) of them had a household income of 1-5 minimum wages. The majority (83.2%, n=475) attended more than six prenatal consultations, but only 86.2% (n=494) said they had received information on breastfeeding. Among children who received other types of milk, 53.8% (n=191) consumed whole cow’s milk; of these, 31.7% (n=113) reported having received orientation from the pediatrician. Cow’s milk consumption was associated with maternal age (women under 18 years old (p=0.015)), income of less than five minimum wages (pObjetivo: Evaluar la frecuencia y los factores asociados al uso de la leche de la vaca integral en niños menores de un año de la ciudad de Fortaleza, Ceará. Métodos: Se realizó un estúdio transversal y analítico con 575 madres de niños menores de un año de edad residentes en Fortaleza, Ceará. Se aplicó un cuestionario semiestructurado para la recogida de datos sociodemográficos, la historia de reproducción de la madre, los datos del parto y del niño. Resultados: La mediana de la edad de las madres fue de 26,5 años con renta familiar entre 1 y 5 sueldos mínimos mensuales para el 80,5% (n=463). La mayoría (83,2%, n=475) realizo más de seis consultas de prenatal pero solo el 86,2% (n=494) se declaró haber recibido informaciones de la lactancia materna. Entre los niños que recibieron otro tipo de leche, el 53,8% (n=191) consumieron la leche de vaca integral y de estes el 31,7% (n=113) refieren haber recibido orientación del pediatra. El consumo de la leche de vaca estuvo relacionado a la edad materna (menores de 18 años de edad, (p=0,015), renta abajo de cinco sueldos mínimos (pObjetivo: Avaliar a frequência e fatores associados ao uso do leite de vaca integral nas crianças menores de um ano na cidade de Fortaleza, Ceará. Métodos: Realizou-se estudo transversal e analítico envolvendo 575 mães de crianças menores de um ano de idade residentes em Fortaleza, Ceará. Aplicou-se questionário semiestruturado para coleta de dados sociodemográficos, história reprodutiva da mãe, dados referentes ao parto e à criança. Resultados: A mediana de idade das mães foi de 26,5 anos, tendo 80,5% (n=463) renda familiar de 1 a 5 salários mínimos. A maior parte (83,2%, n=475) realizou mais de seis consultas de pré-natal, mas apenas 86,2% (n=494) declararam ter recebido informações sobre aleitamento materno. Entre as crianças que receberam outro tipo de leite, 53,8% (n=191) consumiram leite de vaca integral, e destas, 31,7% (n=113) referem ter recebido orientação do pediatra. O consumo do leite de vaca foi relacionado à idade materna (menores de 18 anos de idade, (p=0,015), renda inferior a cinco salários mínimos (

Hospitalização e fatores associados entre residentes de instituições de longa permanência para idosos Hospitalization and risk factors among elderly individuals living in nursing homes

O estudo avaliou a prevalência de internação hospitalar no período de um ano e os fatores associados com base em um censo entre residentes de instituições de longa permanência para idosos em Pelotas, Rio Grande do Sul, Brasil. A internação hospitalar foi avaliada com a pergunta: "Desde <mês> do ano passado, o(a) Sr.(a) baixou em algum hospital?". Dos 521 indivíduos elegíveis, coletou-se informação de 466 (89,4%). A prevalência de hospitalização no último ano foi de 23,9% (IC95%: 19,9-27,8) e associou-se com: incapacidade para atividades básicas vida diária, ocorrência de queda no último ano e o fato de ser ex-fumante. Indivíduos solteiros e separados tiveram proteção para internação hospitalar. Houve também associação inversa do desfecho com autopercepção de saúde. A alta prevalência de internação hospitalar encontrada em indivíduos residentes em instituições de longa permanência para idosos é um importante indicador para o planejamento dos serviços de saúde, de forma a bem atender as demandas de uma população em transição demográfica e epidemiológica.<br>The aim of the present study was to evaluate the prevalence of hospital admissions over a one-year period and associated factors through a survey of elderly subjects living in nursing homes in Pelotas, Rio Grande do Sul State, Brazil. Hospital admissions were assessed using the question: "From <month> last year to today, were you admitted to a hospital?" Out of 521 eligible individuals, information was collected for 466 (89.4%). Prevalence of hospital admissions in the previous 12 months was 23.9% (95%CI: 19.9-27.8). Admissions were directly associated with: inability to perform basic activities of daily living, falls, and history of smoking. Single and divorced individuals were less likely to be hospitalized. There was an inverse association between hospitalization and self-rated health. The high prevalence of hospitalization among elderly subjects living in nursing homes is an important indicator for the organization of health services, in order to ensure high-quality services for a population group experiencing a demographic and epidemiological transition

Swine and Poultry Pathogens: the Complete Genome Sequences of Two Strains of Mycoplasma hyopneumoniae and a Strain of Mycoplasma synoviae

This work reports the results of analyses of three complete mycoplasma genomes, a pathogenic (7448) and a nonpathogenic (J) strain of the swine pathogen Mycoplasma hyopneumoniae and a strain of the avian pathogen Mycoplasma synoviae; the genome sizes of the three strains were 920,079 bp, 897,405 bp, and 799,476 bp, respectively. These genomes were compared with other sequenced mycoplasma genomes reported in the literature to examine several aspects of mycoplasma evolution. Strain-specific regions, including integrative and conjugal elements, and genome rearrangements and alterations in adhesin sequences were observed in the M. hyopneumoniae strains, and all of these were potentially related to pathogenicity. Genomic comparisons revealed that reduction in genome size implied loss of redundant metabolic pathways, with maintenance of alternative routes in different species. Horizontal gene transfer was consistently observed between M. synoviae and Mycoplasma gallisepticum. Our analyses indicated a likely transfer event of hemagglutinin-coding DNA sequences from M. gallisepticum to M. synoviae

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt