Immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) using two-dose primary protocol in children and adolescents (Immunita-002, Brazil): A phase IV six-month follow up.

Introduction: Vaccines are essential for the prevention and control of several diseases, indeed, monitoring the immune response generated by vaccines is crucial. The immune response generated by vaccination against SARS-CoV-2 in children and adolescents is not well defined regarding to the intensity and medium to long-term duration of a protective immune response, which may point out the need of booster doses and might support the decisions in public health. Objective: The study aims to evaluate the immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) in a two-dose primary protocol in children and adolescent aging from 3 to 17 years old in Brazil. Methods: Participants were invited to participate in the research at two public healthcare centers located in Serrana (São Paulo) and Belo Horizonte (Minas Gerais), Brazil. Participants underwent medical interviews to gather their medical history, including COVID-19 history and medical records. Physical exams were conducted, including weight, blood pressure, temperature, and pulse rate measurements. Blood samples were obtained from the participants before vaccination, 1 month after the first dose, and 1, 3, and 6 months after the second dose and were followed by a virtual platform for monitoring post-vaccination reactions and symptoms of COVID-19. SARS-CoV-2 genome from Swab samples of COVID-19 positive individuals were sequenced by NGS. Total antibodies were measured by ELISA and neutralizing antibodies to B.1 lineage and Omicron variant (BA.1) quantified by PRNT and VNT. The cellular immune response was evaluated by flow cytometry by the quantification of systemic soluble immune mediators. Results: The follow-up of 640 participants showed that the CoronaVac vaccine (Sinovac/Butantan Institute) was able to significantly induce the production of total IgG antibodies to SARS-CoV-2 and the production of neutralizing antibodies to B.1 lineage and Omicron variant. In addition, a robust cellular immune response was observed with wide release of pro-inflammatory and regulatory mediators in the early post-immunization moments. Adverse events recorded so far have been mild and transient except for seven serious adverse events reported on VigiMed. Conclusions: The results indicate a robust and sustained immune response induced by the CoronaVac vaccine in children and adolescents up to six months, providing evidences to support the safety and immunogenicity of this effective immunizer.

Anti-asthmatic activity of standardized hydro-ethanolic and aqueous extracts of Stachytarpheta cayennensis (Rich.) Vahl in a murine model.

ETHNOPHARMACOLOGICAL RELEVANCE: Stachytarpheta cayennensis (Verbenaceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory diseases. AIMS OF THE STUDY: To investigate the effects of different doses of standardized hydro-ethanolic (SCH) and aqueous (SCA) extracts of aerial parts of S. cayennensis using a murine ovalbumin (OVA)-induced asthma model. MATERIALS AND METHODS: The major constituents of the plant extracts were identified and standardized by ultra-performance liquid chromatography coupled with mass spectrometry. Balb/c mice were challenged with OVA solution and treated concomitantly by intraperitoneal injection of standardized SCH or SCA extracts at 50, 100, and 200 mg/kg concentrations. OVA-challenged control animals were treated with either dexamethasone (OVA-DEX) or saline solution (OVA-SAL). After challenge, we assessed in vivo bronchial hyperresponsiveness, airway inflammation (number of cells), peribronchial inflammation (histological analysis) and production of OVA-specific IgE and interleukin (IL)-4, IL-5, and IL-13 (ELISA). RESULTS: Acteoside, isoacteoside, and ipolamiide were the major constituents of SCH and SCA. The respective concentrations of acteoside in SCH and SCA were 78 and 98 µg/mL, while those of ipolamiide were 30 and 19 µg/mL. Treatment with 200 mg/kg of SCH or SCA decreased IL-4, IL-5, and IL-13 in lung homogenates. These reductions were accompanied by a lower influx of inflammatory cells (eosinophils, lymphocytes, and macrophages) to the airways and lungs. In addition to the anti-inflammatory effects, administration of SCA, but not SCH, ameliorated the parameters of bronchial hyperresponsiveness and decreased levels of circulating OVA-specific IgE. CONCLUSION: The results presented herein demonstrate for the first time the anti-asthmatic activity of S. cayennensis extracts in a murine model, thereby supporting the ethnopharmacological uses of the plant.

O Desenvolvimento Docente na FMRP-USP: contexto histórico / Faculty Development at Ribeirão Preto School of Medicine at University of São Paulo (FMRP-USP): A contextualized historical review

O objetivo desse artigo é contextualizar historicamente as ações de desenvolvimento docente realizadas na Facul-dade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP) desde sua fundação até a criação do Centro de Desenvolvimento Docente para o Ensino (CDDE) para as Profissões da Saúde, que foi a primeira unidade formal da instituição para a educação para o ensino dos seus professores e preceptores. Apresentamos um pano-rama sobre o conceito atual de desenvolvimento docente, o papel de fundações internacionais de fomento e de regulamentações governamentais locais na consolidação dessas atividades no país, além de ações dos diretores e professores da Faculdade de Medicina, visando a capacitação profissional para o exercício da docência desde a sua fundação. Finalmente, abordamos o contexto de criação do CDDE, os profissionais participantes e dados da partici-pação docente nas cinco primeiras edições do "Módulo Básico" de ensino para as profissões da saúde na FMRP-USP, o primeiro e mais importante programa estruturado de capacitação docente oferecido pelo centro. (AU)

The objective of this article is to historically contextualize Faculty Development (FD) actions carried out at the Ribeirão Preto School of Medicine at University of São Paulo (FMRP-USP), since its foundation up until the creation of the Center for Faculty Development (CDDE) in Health Professions Education (HPE). CDDE is the first formal unit of the institution with the mission to support educators (Faculty Members and Preceptors) to improve their educa-tional practices: to teach, facilitate learning, assess, design curriculum, and evaluate programs. We present here an overview for the concept of Faculty Development, the role of international funding foundations and local govern-ment regulations in the consolidation of these activities in Brazil. We also describe the school administration actions and pioneer Faculty members that created the foundations for the first Faculty Development Center at FMRP-USP. Finally, we address the context of the creation of the CDDE and the describe participants characteristics of the first five editions of the Essentials Skills Module on HPE. (AU)

Momordica charantia L. improves airway hyperresponsiveness and suppresses inflammation in a murine model of allergic asthma.

OBJECTIVE: To evaluate the effect of a hydroethanolic extract of Momordica charantia L. ("bitter melon", Cucurbitaceae) leaves (MCHA) on ovalbumin (OVA)-induced asthma model. Balb/c mice were sensitized twice and challenged for 4 alternate days with OVA and then treated with MCHA (500 mg/kg) for 7 consecutive days. METHODS: Control groups received treatment with normal saline or dexamethasone (2 mg/kg) on the same day. We assessed in vivo bronchial hyperresponsiveness and ex-vivo inflammation and mucus production in bronchoalveolar lavage (BAL), lung homogenates, and lung tissue. RESULTS: MCHA significantly improved airway hyperresponsiveness near baseline levels. MCHA administration significantly improved airway and lung inflammation, demonstrated by decreased total and inflammatory cells in BAL, lower levels of IL-5 and IL-13 in lung homogenate, and fewer inflammatory cells in lung tissue. Additionally, MCHA significantly diminished goblet cells in lung tissue. CONCLUSIONS: Administration of a hydroethanolic extract of M. charantia leaves was effective in treating OVA-induced asthma in an animal model.

Momordica charantia L. improves airway hyperresponsiveness and suppresses inflammation in a murine model of allergic asthma

Objective To evaluate the effect of a hydroethanolic extract of Momordica charantia L. (“bitter melon”, Cucurbitaceae) leaves (MCHA) on ovalbumin (OVA)-induced asthma model. Balb/c mice were sensitized twice and challenged for 4 alternate days with OVA and then treated with MCHA (500 mg/kg) for 7 consecutive days.Methods Control groups received treatment with normal saline or dexamethasone (2 mg/kg) on the same day. We assessed in vivo bronchial hyperresponsiveness and ex-vivo inflammation and mucus production in bronchoalveolar lavage (BAL), lung homogenates, and lung tissue.Results MCHA significantly improved airway hyperresponsiveness near baseline levels. MCHA administration significantly improved airway and lung inflammation, demonstrated by decreased total and inflammatory cells in BAL, lower levels of IL-5 and IL-13 in lung homogenate, and fewer inflammatory cells in lung tissue. Additionally, MCHA significantly diminished goblet cells in lung tissue.Conclusions Administration of a hydroethanolic extract of M. charantia leaves was effective in treating OVA-induced asthma in an animal model (AU)

Driving Pressure-limited Strategy for Patients with Acute Respiratory Distress Syndrome. A Pilot Randomized Clinical Trial.

Rationale: Evidence from observational studies suggests that driving pressure is strongly associated with pulmonary injury and mortality, regardless of positive end-expiratory pressure (PEEP) levels, tidal volume, or plateau pressure. Therefore, it is possible that targeting driving pressure may improve the safety of ventilation strategies for patients with acute respiratory distress syndrome (ARDS). However, the clinical effects of a driving pressure-limited strategy for ARDS has not been assessed in randomized controlled trials.Objectives: To evaluate the feasibility of testing a driving pressure-limited strategy in comparison with a conventional lung-protective ventilation strategy in patients with ARDS and a baseline driving pressure of ≥13 cm H2O.Methods: This was a randomized, controlled, nonblinded trial that included 31 patients with ARDS who were on invasive mechanical ventilation and had a driving pressure of ≥13 cm H2O. Patients allocated to the driving pressure-limited strategy were ventilated with volume-controlled or pressure-support ventilation modes, with tidal volume titrated to 4-8 ml/kg of predicted body weight (PBW), aiming at a driving pressure of 10 cm H2O, or the lowest possible. Patients in the control group were ventilated according to the ARDSNet (Acute Respiratory Distress Syndrome Network) protocol, using a tidal volume of 6 ml/kg PBW, which was allowed to be set down to 4 ml/kg PBW if the plateau pressure was >30 cm H2O. The primary endpoint was the driving pressure on Days 1-3.Results: Sixteen patients were randomized to the driving pressure-limited group and 15 were randomized to the conventional strategy group. All patients were considered in analyses. Most of the patients had mild ARDS with a mean arterial oxygen tension/fraction of inspired oxygen ratio of 215 (standard deviation [SD] = 95). The baseline driving pressure was 15.0 cm H2O (SD = 2.6) in both groups. In comparison with the conventional strategy, driving pressure from the first hour to the third day was 4.6 cm H2O lower in the driving pressure-limited group (95% confidence interval [CI], 6.5 to 2.8; P < 0.001). From the first hour up to the third day, tidal volume in the driving pressure-limited strategy group was kept lower than in the control group (mean difference [ml/kg of PBW], 1.3; 95% CI, 1.7 to 0.9; P < 0.001). We did not find statistically significant differences in the incidence of severe acidosis (pH < 7.10) within 7 days (absolute difference -12.1; 95% CI, -41.5 to -17.3) or any clinical secondary endpoint.Conclusions: In patients with ARDS, a trial assessing the effects of a driving pressure-limited strategy using very low tidal volumes versus a conventional ventilation strategy on clinical outcomes is feasible.Clinical trial registered with ClinicalTrials.gov (NCT02365038).

Validation of the Pulmonary Embolism Severity Index for risk stratification after acute pulmonary embolism in a cohort of patients in Brazil.

OBJECTIVE: To validate the Pulmonary Embolism Severity Index (PESI), which was developed for risk stratification after acute pulmonary embolism (PE), for use in Brazil. METHODS: This was a single-center retrospective study involving patients admitted to the emergency department with acute PE. The original and simplified versions of the PESI were calculated using hospital admission data from medical records. The outcome measure was the overall 30-day mortality rate. RESULTS: We included 123 patients. The mean age was 57 ± 17 years, and there was a predominance of females, who accounted for 60% of the cohort. There were 28 deaths, translating to an overall 30-day mortality rate of 23%. In the cluster analysis by risk class, overall 30-day mortality was 2.40% for classes I-II, compared with 20.00% for classes III-IV-V (relative risk [RR] = 5.9; 95% CI: 1.88-18.51; p = 0.0002). When we calculated overall 30-day mortality using the simplified version (0 points vs. ≥ 1 point), we found it to be 3.25% for 0 points and 19.51% for ≥ 1 point (RR = 2.38; 95% CI: 0.89-6.38; p = 0.06). Using the original version, a survival analysis showed that risk classes I and II presented similar Kaplan-Meier curves (p = 0.59), as did risk classes III, IV, and V (p = 0.25). However, the curve of the clusters based on the original version, showed significantly higher mortality in the III-IV-V classes than in the I-II classes (RR = 7.63; 95% CI: 2.29-25.21; p = 0.0001). The cluster analysis based on the original version showed a greater area under the ROC curve than did the analysis based on the simplified version (0.70; 95% CI: 0.62-0.77 vs. 0.60; 95% CI: 0.51-0.67; p = 0.05). CONCLUSIONS: The PESI adequately predicted the prognosis after acute PE in this sample of the population of Brazil. The cluster analysis based on the original version is the most appropriate analysis in this setting.

The ethanolic extract from Erythrina mulungu Benth. flowers attenuates allergic airway inflammation and hyperresponsiveness in a murine model of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Erythrina mulungu Benth. ("mulungu", Fabaceae) is a Brazilian native species with ethnopharmacological use for respiratory diseases. However, the effects of E. mulungu on the respiratory were never studied. AIMS OF THE STUDY: To evaluate the effects of an ethanolic extract from flowers of E. mulungu in ovalbumin (OVA)-induced asthma in mice, and to study the mechanisms involved. MATERIALS AND METHODS: OVA-sensitized mice were intraperitoneally (i.p.) treated with four doses (200, 400, 600, and 800 mg/kg) of the E. mulungu extract or dexamethasone (DEXA, 2 mg/kg) during seven consecutive days and simultaneously challenged with intranasal OVA. Bronchial hyperresponsiveness was evaluated in vivo, 24 h after the last OVA challenge. Bronchoalveolar lavage (BAL) was collected for counting the number of total and differential inflammatory cells. Blood was collected for measurement of anti-OVA IgE levels. Levels of cytokines interleukin (IL)- 4, IL-5, IL-10, IL-13, and interferon (INF)-γ were measured in pulmonary homogenate by ELISA. The recruitment of inflammatory cells to the lung tissue was determined using hematoxylin and eosin staining (H&E). The extract's chromatographic profile was evaluated by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). RESULTS: The treatment with E. mulungu extract significantly reduced bronchial hyperresponsiveness, significantly reduced the number of leukocytes, eosinophils, and lymphocytes in BAL, and significantly decreased the levels of IL-4 and IL-5, while increased levels of IL-13 and INF-γ. In addition, E. mulungu significantly decreased the cellular inflammatory infiltration in the lung tissue. Erysotrine, erysotrine-N-oxide, and hypaphorine were the major constituents identified in the extract. CONCLUSION: Collectively, these results confirm the potential of E. mulungu for asthma treatment, through modulation of inflammatory response, supporting its ethnopharmacological use for respiratory diseases.

Validation of the Pulmonary Embolism Severity Index for risk stratification after acute pulmonary embolism in a cohort of patients in Brazil / Validação do Pulmonary Embolism Severity Index para a estratificação de risco após tromboembolia pulmonar aguda em uma coorte no Brasil

ABSTRACT Objective: To validate the Pulmonary Embolism Severity Index (PESI), which was developed for risk stratification after acute pulmonary embolism (PE), for use in Brazil. Methods: This was a single-center retrospective study involving patients admitted to the emergency department with acute PE. The original and simplified versions of the PESI were calculated using hospital admission data from medical records. The outcome measure was the overall 30-day mortality rate. Results: We included 123 patients. The mean age was 57 ± 17 years, and there was a predominance of females, who accounted for 60% of the cohort. There were 28 deaths, translating to an overall 30-day mortality rate of 23%. In the cluster analysis by risk class, overall 30-day mortality was 2.40% for classes I-II, compared with 20.00% for classes III-IV-V (relative risk [RR] = 5.9; 95% CI: 1.88-18.51; p = 0.0002). When we calculated overall 30-day mortality using the simplified version (0 points vs. ≥ 1 point), we found it to be 3.25% for 0 points and 19.51% for ≥ 1 point (RR = 2.38; 95% CI: 0.89-6.38; p = 0.06). Using the original version, a survival analysis showed that risk classes I and II presented similar Kaplan-Meier curves (p = 0.59), as did risk classes III, IV, and V (p = 0.25). However, the curve of the clusters based on the original version, showed significantly higher mortality in the III-IV-V classes than in the I-II classes (RR = 7.63; 95% CI: 2.29-25.21; p = 0.0001). The cluster analysis based on the original version showed a greater area under the ROC curve than did the analysis based on the simplified version (0.70; 95% CI: 0.62-0.77 vs. 0.60; 95% CI: 0.51-0.67; p = 0.05). Conclusions: The PESI adequately predicted the prognosis after acute PE in this sample of the population of Brazil. The cluster analysis based on the original version is the most appropriate analysis in this setting.

RESUMO Objetivo: Pulmonary Embolism Severity Index (PESI) foi desenvolvido para a estratificação de risco após tromboembolia pulmonar (TEP) aguda. Nosso objetivo foi validá-lo para uso no Brasil. Métodos: Estudo retrospectivo unicêntrico incluindo pacientes com TEP admitidos numa unidade de emergência. O PESI (versão original e simplificada) foi calculado utilizando-se dados dos prontuários na admissão hospitalar. O desfecho analisado foi mortalidade geral em 30 dias (MG30). Resultados: Foram incluídos 123 pacientes, com média de idade de 57 ± 17 anos, predomínio do sexo feminino (60%) e MG30 de 28 óbitos (23%). Na análise agrupada, a MG30 (classes I-II vs. III-IV-V) foi de 2,40% vs. 20,00% (risco relativo [RR] = 5,9; IC95%: 1,88-18,51; p = 0,0002). A MG30 na versão simplificada (0 vs. ≥ 1 ponto) foi de 3,25% vs. 19,51% (RR = 2,38; IC95%: 0,89-6,38; p = 0,06). A análise da sobrevida mostrou que as curvas de Kaplan-Meier foram semelhantes nas classes I e II (p = 0,59) e entre as classes III, IV e V (p = 0,25). A curva da versão original agrupada mostrou que a MG30 foi significativamente maior no grupo III-IV-V que no grupo I-II (RR = 7,63; IC95%: 2,29-25,21; p = 0,0001). A análise agrupada da versão original mostrou área sob a curva ROC maior que a da versão simplificada (0,70; IC95%: 0,62-0,77 vs. 0,60; IC95%: 0,51-0,67; p = 0,05). Conclusões: O PESI mensurou adequadamente o prognóstico de MG30 após TEP aguda nesta amostra da população brasileira. A utilização da versão original agrupada foi a mais adequada nesse cenário.

Avaliação Somativa de Habilidades Cognitivas: Experiência Envolvendo Boas Práticas para a Elaboração de Testes de Múltipla Escolha e a Composição de Exames / Summative Assessment of Cognitive Skills: an Experience Involving Good Practices for Writing Multiple Choice Tests and Exam Composition

RESUMO As questões objetivas ou testes de múltipla escolha com somente uma alternativa correta constituem um dos métodos mais utilizados em todo o mundo em exames destinados a avaliar habilidades cognitivas, especialmente nas avaliações somativas. Provas que contêm predominantemente questões objetivas de múltipla escolha são utilizadas sobretudo nos exames em que muita coisa está em jogo, como concursos vestibulares, provas finais de cursos de graduação e exames próprios dos concursos de ingresso à residência médica ou de obtenção de título de especialista. Esta ampla difusão justifica-se pelo fato de os exames compostos com este tipo de questão preencherem mais completamente os requisitos de validade e de fidedignidade, além de terem vantagens quanto à viabilidade ou factibilidade, particularmente em provas com grande número de candidatos. No entanto, os requisitos de validade e fidedignidade, em especial, somente são preenchidos adequadamente quando se seguem normas próprias das boas práticas de construção de exames e de elaboração dos testes propriamente ditos. Neste artigo se descrevem algumas das boas práticas na elaboração de testes de múltipla escolha, baseadas em fontes da literatura nacional e internacional, bem como na experiência dos autores. Apresenta-se e se discute um conjunto de regras práticas para construir questões de múltipla escolha de boa qualidade no que se refere à forma e ao conteúdo e se comenta como compor tabelas de especificação. Este tipo particular de matriz da avaliação permite verificar o alinhamento entre os temas abordados na prova e os objetivos curriculares ou o que se espera que os estudantes/candidatos dominem, o que configura um importante indicador de validade. Apresenta-se também uma experiência bem-sucedida de trabalho em grupo na organização de exames que utilizam este tipo de questão, como exemplo de desenvolvimento de processo organizado para obtenção de questões de melhor qualidade, que também contribuiu para o desenvolvimento docente no campo de avaliação da aprendizagem.

ABSTRACT Objective items or multiple choice questions with just one correct answer are among the most widely used methods for cognitive skills assessment, especially in exams designed for summative purposes. Assessments related to the cognitive domain using multiple choice questions are mostly used in high-stake exams, i.e. where the risks of failing are associated with serious consequences for the candidates. The widespread use of objective items for assessing learning in the cognitive domain may be explained by the fact that this exam modality fulfills both validity and reliability requirements, with the additional advantage that they are practical for use in exams with large numbers of candidates. Nevertheless, the validity and reliability requirements, in particular, will only be properly fulfilled when the process of writing multiple choice questions follows the rules of good practices for constructing exams and writing tests. This manuscript describes some of the rules for developing high quality multiple choice tests, based on both national and international published sources, as well as on the author's experience. These rules relate to the content, language and presentation of the questions. This paper also addresses the importance of following appropriate rules for blueprinting construction, in order to show the alignment between assessment and curriculum and thereby contribute to meeting the validity requirements. It also briefly describes and discusses a successful experience of team work for constructing items and organizing exams. This experience exemplifies the combination of an organized process for constructing high quality questions for a well-balanced examination with an institutional strategy for faculty development in the field of learning assessment.

Vascular and ventilatory mechanical responses in three different stages of pulmonary development in the rabbit model of congenital diaphragmatic hernia 1.

PURPOSE: To evaluate the vascular ventilatory response in different stages of lung development and to compare them to the neonates with congenital diaphragmatic hernia (CDH) in a rabbit model. METHODS: New Zealand rabbits were divided into 8 groups (n=5): E25, E27, E30, and CDH. All groups were ventilated on a FlexiVent (Scireq, Montreal, QC, Canada), compounding the other 4 groups. The CDH surgery was performed at E25 and the harvest at E30. Dynamic compliance (CRS), dynamic elastance (ERS) and dynamic resistance (RRS) were measured every 4 min/24 min. Median wall thickness (MWT) and airspace were measured. ANOVA Bonferroni tests were used to perform statistical analysis. Significance was considered when p<0.05. RESULTS: CRS was higher in E30 compared to all other groups (p<0.05). CRS and RRS of CDH and E27 were similar and were higher in E25 (p<0.05). MWT was decreased according to the gestational age, was increased in E27V and E30V (p<0.05) and decreased in CDHV (p<0.05), airspace was decreased in E25 and increased in all ventilated groups (p<0.05). CONCLUSIONS: The ventilation response of congenital diaphragmatic hernia is like the pseudoglandular stage of the lung development. These findings add information about the physiology of pulmonary ventilation in CDH.

Vascular and ventilatory mechanical responses in three different stages of pulmonary development in the rabbit model of congenital diaphragmatic hernia

Abstract Purpose: To evaluate the vascular ventilatory response in different stages of lung development and to compare them to the neonates with congenital diaphragmatic hernia (CDH) in a rabbit model. Methods: New Zealand rabbits were divided into 8 groups (n=5): E25, E27, E30, and CDH. All groups were ventilated on a FlexiVent (Scireq, Montreal, QC, Canada), compounding the other 4 groups. The CDH surgery was performed at E25 and the harvest at E30. Dynamic compliance (CRS), dynamic elastance (ERS) and dynamic resistance (RRS) were measured every 4 min/24 min. Median wall thickness (MWT) and airspace were measured. ANOVA Bonferroni tests were used to perform statistical analysis. Significance was considered when p<0.05. Results: CRS was higher in E30 compared to all other groups (p<0.05). CRS and RRS of CDH and E27 were similar and were higher in E25 (p<0.05). MWT was decreased according to the gestational age, was increased in E27V and E30V (p<0.05) and decreased in CDHV (p<0.05), airspace was decreased in E25 and increased in all ventilated groups (p<0.05). Conclusions: The ventilation response of congenital diaphragmatic hernia is like the pseudoglandular stage of the lung development. These findings add information about the physiology of pulmonary ventilation in CDH.

Experiência de formação docente na pós-graduação e pesquisa em educação: projeto Capes Pró-Ensino na Saúde da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil / Experience of teacher education in graduate studies and research in education: Capes Pro-Ensino na Saude project, School of Medicine at the University of Sao Paulo, Ribeirao Preto, Brazil / Experiencia de formación docente en el postgrado e investigación en educación: proyecto Capes Pró-Ensino na Saúde de la Facultad de Medicina de Ribeirão Preto, Universidad de São Paulo, Brasil

Este artigo descreve a experiência do projeto Pró-Ensino na Saúde (Capes-Edital 024/2010) da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Entre 2011 e 2016 o projeto formou quatro mestres e cinco doutores, além de criar disciplinas abordando tópicos de ensino-aprendizagem na saúde. Nesse período, consolidou-se grupo de pesquisa em educação na saúde, que vem desenvolvendo projetos específicos e publicando artigos inéditos e revisões sobre temas relevantes à docência na saúde. Todos os objetivos do edital Capes foram alcançados, apesar das dificuldades enfrentadas, como a pouca flexibilidade da pós-graduação na universidade, o que restringiu a admissão de pós-graduandos e o credenciamento de novos orientadores. Mesmo após o término do projeto, manteve-se o grupo de ensino e pesquisa, que continua contribuindo para a valorização da formação docente na pós-graduação e da pesquisa na área de ensino na saúde.(AU)

This article describes the experience of the Capes Pro-Ensino na Saude project (Capes notice 024/2010) at the School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil. Between 2011 and 2016 the project provided the degrees of four masters and five doctors, in addition to creating subjects approaching topics on teaching-learning in health. In this period, there was the consolidation of the research group in health education, which has been developing specific projects and publishing original articles and reviews on subjects relevant to teaching in health. All objectives of the Capes notice were met, despite the difficulties faced such as little flexibility on the part of the graduate program in the university, which restricted the admission of graduate students and the accreditation of new advisors. The teaching and research group was kept even after the end of the project, and it still contributes to adding value to the teacher education in graduate studies and research in the health education area.(AU)

Este artículo describe la experiencia del proyecto Capes Pró-Ensino na Saúde (Capes-Pliego de Condiciones 024/2010) de la Facultad de Medicina de Ribeirão Preto, Universidad de São Paulo. Entre 2011 y 2016 se graduaron en el proyecto cuatro alumnos de maestría y dos de doctorado, además de crear asignaturas abordando tópicos de enseñanza-aprendizaje en salud. En ese período se consolidó el grupo de investigación en educación en salud que ha desarrollado proyectos específicos y publicado artículos inéditos y revisiones sobre temas relevantes a la docencia en salud. Todoslos objetivos del edicto Capes se alcanzaron, a pesar de las dificultades enfrentadas, tales como la poca flexibilidad del postgrado en la universidad, lo que restringió la admisión de alumnos de postgrado y la acreditación de nuevos orientadores. Aún después del final del proyecto, se mantuvo el grupo de enseñanza e investigación que continúa contribuyendo con la valorización de la formación docente en el postgrado y de la investigación en el área de enseñanza en salud.(AU)

Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.

Importance: The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain. Objective: To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. Design, Setting, and Participants: Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. Interventions: An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning. Main Outcomes and Measures: The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality. Results: A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, -1.1; 95% CI, -2.1 to -0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. Conclusions and Relevance: In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. Trial Registration: clinicaltrials.gov Identifier: NCT01374022.

A standardized methanol extract of Eclipta prostrata (L.) L. (Asteraceae) reduces bronchial hyperresponsiveness and production of Th2 cytokines in a murine model of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrata (L.) L. (Asteraceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory illnesses. AIMS OF THE STUDY: To investigate the effects of different doses of a standardized extract of E. prostrata using a murine model of allergen induced asthma. MATERIALS AND METHODS: Balb/c mice were sensitized twice with ovalbumin (OVA) administered intraperitoneally and challenged over four alternate days with nasal instillations of OVA solution. The standardized methanol extract of E. prostrata was administered in doses of 100, 250 and 500mgkg-1 concomitantly with nasal instillation over seven consecutive days. Control animals were treated with dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, allergen sensitization, airway and lung inflammation, mucous secretion and airway remodeling were assessed. RESULTS: The concentrations of chemical markers in the standardized methanol extract were 0.02% oroboside, 1.69% demethylwedelolactone and 1.71% wedelolactone. Treatment with 250mgkg-1 of extract, which provided 0.745, 4.22 and 4.30mgkg-1day-1 of oroboside, demethylwedelolactone and wedelolactone, respectively, significantly reduced (P<0.05) respiratory resistance and elastance. Such effects were comparable with those produced by dexamethasone. The total number of inflammatory cells and eosinophils in the bronchoalveolar lavage and the concentrations of interleukin (IL)-4, IL-5 and IL-13 in lung homogenate were significantly reduced (P<0.05) by the methanol extract of E. prostrata. CONCLUSION: The results presented herein demonstrate for the first time the anti-inflammatory activity of E. prostrata in a murine model of asthma, thereby supporting the ethnopharmacological uses of the plant.

A case presentation of a fatal dengue myocarditis showing evidence for dengue virus-induced lesion.

Dengue is a prevalent arthropod-borne viral disease in tropical and subtropical areas of the globe. Dengue clinical manifestations include asymptomatic infections; undifferentiated fever; dengue fever, which is characterized by fever, headache, retroorbital pain, myalgia, and arthralgia; and a severe form of the disease denominated dengue haemorrhagic fever/dengue shock syndrome, characterized by haemoconcentration, thrombocytopenia, and bleeding tendency. However, atypical manifestations, such as liver, central nervous system, and cardiac involvement, have been increasingly reported. We report an atypical and rare presentation of dengue disease marked by a dramatic and fatal cardiogenic shock due to acute myocarditis. Histopathological analysis of heart tissue showed several multifocal areas of muscle necrosis and intense interstitial oedema associated with clusters of virus particles inside the cardiomyocytes and in the interstitial space, providing evidence of a possible direct action of dengue virus on myocardium.

Evaluation of cardiac involvement during dengue viral infection.

BACKGROUND: Dengue is a disease whose clinical manifestations range from asymptomatic infections to a severe disease. There have been some previous reports of myocardial involvement in dengue, but this association has not been completely established. METHODS: From January to July of 2011, patients hospitalized with dengue, confirmed through dengue nonstructural protein 1 and/or immunoglobulin M detection, were included in this study and troponin I and N terminal fragment of B-type natriuretic peptide levels were determined. Patients with abnormal biomarkers underwent echocardiography and when any abnormality was detected, they underwent cardiac magnetic resonance imaging. RESULTS: Eighty-one patients were evaluated and 12 patients (15%) presented with elevated biomarker levels. Compared to controls, they had higher leukocyte (P < .001) and platelet counts (P = .005); higher C-reactive protein (P = .02), and a lower viral load (P = .03). There was no difference according to clinical dengue classification; dengue hemorrhagic fever/dengue shock syndrome severity; duration of symptoms; or prevalence of secondary infection between the 2 groups. Two patients died secondary to cardiogenic shock before imaging studies. Necroscopic findings were compatible to myocarditis in both, and immunohistochemistry for dengue virus showed increased staining on mononuclear cells located in the myocardial tissue. Of the 10 patients who underwent echocardiography, depressed left ventricular ejection fraction (LVEF) was identified in 1, left ventricular segmental abnormalities with preserved LVEF in 2, and an important pericardial effusion with tamponade in another. Cardiac involvement was confirmed by CMR in these 4 patients. CONCLUSIONS: Dengue viruses were shown to cause cardiac disease with clinical manifestations ranging from mild elevation of biomarkers to myocarditis and/or pericarditis.

Bronchial provocation tests in clinical practice.

Bronchial hyperresponsiveness, which consists of an exaggerated response of the airways to bronchoconstrictor stimuli, is one of the main characteristics of asthma, presented in nearly all asthmatic patients. Bronchial hyperresponsiveness may also be present in other diseases, such as allergic rhinitis, chronic obstructive pulmonary disease, cystic fibrosis, heart failure and respiratory infection, and with some medications, such as ß-blockers. Bronchial provocation tests (also known as bronchial challenges) are used to evaluate bronchial responsiveness. These tests have become increasingly used over the last 20 years, with the development and validation of accurate, safe and reproducible tests, and with the publication of well-detailed protocols. Several stimuli can be used in a bronchial challenge, and they are classified as direct and indirect stimuli. There are many indications for a bronchial challenge. In this review, we discuss the main differences between direct and indirect stimuli, and the use of bronchial challenges in clinical practice, especially for confirming diagnoses of asthma, exercise-induced bronchoconstriction and cough-variant asthma, and for use among elite-level athletes.

Bronchial provocation tests in clinical practice / Teste de broncoprovocação na prática clínica

Bronchial hyperresponsiveness, which consists of an exaggerated response of the airways to bronchoconstrictor stimuli, is one of the main characteristics of asthma, presented in nearly all asthmatic patients. Bronchial hyperresponsiveness may also be present in other diseases, such as allergic rhinitis, chronic obstructive pulmonary disease, cystic fibrosis, heart failure and respiratory infection, and with some medications, such as β-blockers. Bronchial provocation tests (also known as bronchial challenges) are used to evaluate bronchial responsiveness. These tests have become increasingly used over the last 20 years, with the development and validation of accurate, safe and reproducible tests, and with the publication of well-detailed protocols. Several stimuli can be used in a bronchial challenge, and they are classified as direct and indirect stimuli. There are many indications for a bronchial challenge. In this review, we discuss the main differences between direct and indirect stimuli, and the use of bronchial challenges in clinical practice, especially for confirming diagnoses of asthma, exercise-induced bronchoconstriction and cough-variant asthma, and for use among elite-level athletes.

Hiperresponsividade brônquica, caracterizada por uma resposta exagerada das vias aéreas a um estímulo broncoconstritor, é uma das principais características da asma, presente em praticamente todos pacientes asmáticos. A hiperresponsividade brônquica pode estar presente também em outras doenças, como rinite alérgica, doença pulmonar obstrutiva crônica, fibrose cística, insuficiência cardíaca, infecção respiratória e com o uso de algumas medicações, como β-bloqueadores. Os testes de broncoprovocação são utilizados para determinação da responsividade brônquica, e têm sido cada vez mais utilizados nos últimos 20 anos com o desenvolvimento e validação de testes acurados, seguros e reprodutíveis e com a publicação de protocolos bem detalhados. Diversos estímulos podem ser utilizados em um teste de broncoprovocação, sendo classificados em estímulos diretos e indiretos. Existem inúmeras indicações para um teste de broncoprovocação. Nesta revisão, nós discutimos as principais diferenças dos estímulos diretos e indiretos e o uso desses testes na prática clínica, especialmente para a confirmação de asma, broncoconstrição induzida por exercício, tosse variante de asma e em atletas de elite.

Investigation of factors associated with difficult-to-control asthma.

OBJECTIVE: To determine the prevalence of factors associated with difficult-to-control asthma. METHODS: Patients with severe asthma were selected from the outpatient asthma clinic of the Ribeirão Preto School of Medicine Hospital das Clínicas. The patients were divided into two groups: controlled severe asthma and difficult-to-control severe asthma. After new attempts to optimize the severe asthma treatment, a questionnaire was applied, and additional tests for factors associated with difficult-to-control asthma, such as environmental and occupational exposure, smoking history, social factors, rhinitis/sinusitis, gastroesophageal reflux disease (GERD), obstructive sleep apnea, congestive heart failure (CHF), pulmonary embolism, cystic fibrosis, vocal cord dysfunction, alpha-1 antitrypsin deficiency, and Churg-Strauss syndrome, were performed. RESULTS: 77 patients with severe asthma were selected, of which 47 suffered from hard-to-control asthma, being 68.1% female, with mean age of 44.4 years (+/-14.4), and forced expiratory volume in one second of 54.7% (+/-18.3). The most factors most often associated with difficult-to-control asthma were noncompliance with treatment (68%), rhinitis/sinusitis (57%), GERD (49%), environmental exposure (34%), occupational exposure (17%), smoking history (10%), obstructive sleep apnea (2%), and CHF (2%). At least one of these factors was identified in every case. CONCLUSIONS: Noncompliance with treatment was the factor most often associated with difficult-to-control asthma, underscoring the need to investigate comorbidities in the evaluation of patients with this form of the disease.