γδ T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ γδ T cells in sepsis.

Preterm infants are at high risk of developing neonatal sepsis. γδ T cells are thought to be an important set of effector cells in neonates. Here, γδ T cells were investigated in a longitudinal cohort of preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During the first year of life, the Vγ9Vδ2 T cell subset showed dynamic phenotypic changes and elevated levels of fetal-derived Vγ9Vδ2 T cells were evident in infants with sepsis. Single-cell transcriptomics identified HLA-DRhiCD83+ γδ T cells in neonatal sepsis, which expressed genes related to antigen presentation. In vitro assays showed that CD83 was expressed on activated Vγ9Vδ2 T cells in preterm and term neonates, but not in adults. In contrast, activation of adult Vγ9Vδ2 T cells enhanced CD86 expression, which was presumably the key receptor to induce CD4 T cell proliferation. Together, we provide a map of the maturation of γδ T cells after preterm birth and highlight their phenotypic diversity in infections.

Waterpipe and cigarette epigenome analysis reveals markers implicated in addiction and smoking type inference.

Waterpipe smoking is frequent in the Middle East and Africa with emerging prevalence worldwide. The epigenome acts as a molecular sensor to exposures and a crucial driver in several diseases. With the widespread use of waterpipe smoking, it is timely to investigate its epigenomic markers and their role in addiction, as a central player in disease prevention and therapeutic strategies. DNA methylome-wide profiling was performed on an exposure-rich population from the Middle East, constituting of 216 blood samples split equally between never, cigarette-only and waterpipe-only smokers. Waterpipe smokers showed predominantly distinct epigenetic markers from cigarette smokers, even though both smoking forms are tobacco-based. Moreover, each smoking form could be accurately (∼90 %) inferred from the DNA methylome using machine learning. Top markers showed dose-response relationship with extent of smoking and were validated using independent technologies and additional samples (total N = 284). Smoking markers were enriched in regulatory regions and several biological pathways, primarily addiction. The epigenetically altered genes were not associated with genetic etiology of tobacco use, and the methylation levels of addiction genes, in particular, were more likely to reverse after smoking cessation. In contrast, other epigenetic markers continued to feature smoking exposure after cessation, which may explain long-term health effects observed in former smokers. This study reports, for the first time, blood epigenome-wide markers of waterpipe smokers and reveals new markers of cigarette smoking, with implications in mechanisms of addiction and the capacity to discriminate between different smoking types. These markers may offer actionable targets to reverse the epigenetic memory of addiction and can guide future prevention strategies for tobacco smoking as the most preventable cause of illnesses worldwide.

The multisensory regulation of unconventional T cell homeostasis.

Unconventional T cells typically group γδ T cells, invariant Natural Killer T cells (NKT) and Mucosal Associated Invariant T (MAIT) cells. With their pre-activated status and biased tropism for non-lymphoid organs, they provide a rapid (innate-like) and efficient first line of defense against pathogens at strategical barrier sites, while they can also trigger chronic inflammation, and unexpectedly contribute to steady state physiology. Thus, a tight control of their homeostasis is critical to maintain tissue integrity. In this review, we discuss the recent advances of our understanding of the factors, from neuroimmune to inflammatory regulators, shaping the size and functional properties of unconventional T cell subsets in non-lymphoid organs. We present a general overview of the mechanisms common to these populations, while also acknowledging specific aspects of their diversity. We mainly focus on their maintenance at steady state and upon inflammation, highlighting some key unresolved issues and raising upcoming technical, fundamental and translational challenges.

Territórios Saudáveis e Sustentáveis (TSS) no Distrito Federal: agroecologia e impacto dos agrotóxicos / Healthy and Sustainable Territories (TSS) in the Federal District: agroecology and the impact of pesticides

RESUMO O modelo agrícola predominante no Brasil apresenta disparidades sociais, econômicas e ambientais acentuadas. Tal cenário consiste em um grande desafio para o avanço da agroecologia, um dos caminhos apontados pelas Nações Unidas para o alcance dos Objetivos de Desenvolvimento Sustentável (ODS) e o desenvolvimento territorial de forma sustentável. Assim, o presente estudo teve como objetivo analisar os limites e os desafios na implantação de estratégias territoriais sob a ótica dos Territórios Saudáveis e Sustentáveis (TSS), tendo como eixo estruturante a controvérsia agroecologia x agrotóxicos. O artigo enfoca sua análise na Região Integrada de Desenvolvimento do Distrito Federal e Entorno (Ride-DF), na forma de pesquisa do tipo prospectiva, com revisão de literatura e recolha documental pertinente. Conclui-se que, a despeito do seu potencial, são escassas as informações sobre a temática, especialmente na efetividade e eficácia da estratégia de implantação dos TSS e o uso da agroecologia como suporte. O estudo depreende ainda que há a necessidade de aprofundar a realização de novas pesquisas e a construção de estratégia de intervenção territorial sob a ótica dos TSS.

ABSTRACT The predominant agricultural model in Brazil presents marked social, economic, and environmental disparities. This scenario consists of a great challenge for the advancement of Agroecology, one of the ways pointed out by the United Nations for the achievement of the Sustainable Development Goals (SDGs) and the territorial development in a sustainable way. Thus, the present study aimed to analyze the limits and challenges in the implementation of territorial strategies from the perspective of Healthy and Sustainable Territories (TSS), having the agroecology vs. agrochemicals controversy as a structuring axis. The essay focuses its analysis on the Integrated Development Region of the Federal District and Surroundings (RideDF), in the form of prospective research, with literature review and pertinent documentary collection. It is concluded that, in spite of its potential, information on the theme is scarce, especially on the effectiveness and efficiency of the TSS implementation strategy and the use of Agroecology as a support. The study also concludes that there is a need to deepen the accomplishment of new research and the construction of new territorial intervention strategies from the perspective of the TSS.

International regulatory situation of pesticides authorized for use in Brazil: potential for damage to health and environmental impacts. / Situação regulatória internacional de agrotóxicos com uso autorizado no Brasil: potencial de danos sobre a saúde e impactos ambientais.

The Brazilian legislation does not provide for a periodic review of the registration of pesticides and, even nowadays, products banned in other countries are still used. Based on the pesticide active substances registered in the country, the present study investigated the international regulatory situation in the following member countries: Organization for Economic Co-operation and Development (OECD), European Community, and the BRICS (Brazil, Russia, India, China, and South Africa). Moreover, we sought to relate the main chronic effects to human health and the environment of the most commercialized pesticide active substances in Brazil in lists of classification of carcinogenic potential (US Environmental Protection Agency - USEPA and International Agency for Research on Cancer - IARC), endocrine disruption, and candidates for substitution, both from the European Community. A total of 399 pesticide active substances registered in Brazil for agricultural use were identified, excluding microbiological and biological control agents. Of these, the percentage of unauthorized pesticide active substances according to countries is as follows: 85.7% in Iceland; 84.7% in Norway; 54.5% in Switzerland; 52.6% in India; 45.6% in Turkey; 44.4% in Israel; 43.4% in New Zealand; 42.4% in Japan; 41.5% in the European Community; 39.6% in Canada; 38.6% in China; 35.8% in Chile; 31.6% in Mexico; 28.6% in Australia; and 25.6% in the United States. 120 pesticide active substances were related to damage to health and the environment. Considering the pesticide active substances for which commercialization data are available in the country, 67.2% of this volume is associated with at least one serious chronic damage assessed in this study. The results of the present study indicate the need for promoting transparency of international databases, regarding the motivations of the respective regulatory decisions and the Brazilian regulatory bodies to reevaluate the registration of obsolete products and to strengthen public policies related to the reduction of the use of pesticides.

A legislação brasileira não prevê revisão periódica do registro dos agrotóxicos e, ainda hoje, são utilizados produtos proibidos em outros países. Partindo dos ingredientes ativos de agrotóxicos registrados no país, o presente estudo investigou a situação regulatória internacional nos países-membros da Organização para a Cooperação e Desenvolvimento Econômico (OCDE), da Comunidade Europeia e BRICS. Também se buscou relacionar os principais efeitos crônicos à saúde humana e ao meio ambiente dos ingredientes ativos de agrotóxicos mais comercializados no Brasil, em listas de classificação de potencial cancerígeno (Agência de Proteção Ambiental dos Estados Unidos - USEPA e Agência Internacional de Pesquisa em Câncer - IARC), desregulação endócrina e candidatos para substituição (estes dois últimos da Comunidade Europeia). Foram identificados 399 ingredientes ativos de agrotóxicos registrados no Brasil para uso agrícola, excluindo-se os microbiológicos e agentes biológicos de controle. Destes, não têm autorização 85,7% na Islândia, 84,7% na Noruega, 54,5% na Suíça, 52,6% na Índia, 45,6% na Turquia, 44,4% em Israel, 43,4% na Nova Zelândia, 42,4% no Japão, 41,5% na Comunidade Europeia, 39,6% no Canadá, 38,6% na China, 35,8% no Chile, 31,6% no México, 28,6% na Austrália e 25,6% nos Estados Unidos. Foram relacionados a danos à saúde e ao ambiente 120 ingredientes ativos de agrotóxicos. Considerando os ingredientes ativos de agrotóxicos para os quais estão disponíveis dados de comercialização no país, 67,2% deste volume está associado a pelo menos um dano crônico grave avaliado neste estudo. Os resultados do presente estudo indicam a necessidade de promover a transparência das bases de dados internacionais, no que tange às motivações para as respectivas decisões regulatórias e os órgãos reguladores brasileiros reavaliarem o registro de produtos obsoletos, fortalecendo políticas públicas relacionadas à redução do uso de agrotóxicos.

La legislación brasileña no prevé una revisión periódica del registro de los pesticidas e incluso hoy se utilizan productos prohibidos en otros países. Partiendo de los ingredientes activos de pesticidas registrados en el país, el presente estudio investigó la situación regulatoria internacional en los siguientes países-miembros: Organización para la Cooperación y Desarrollo Económico (OCDE), Comunidad Europea, y BRICS. También se buscó relacionar los principales efectos crónicos para la salud humana y en el medio ambiente de los ingredientes activos de pesticidas más comercializados en Brasil en listas de clasificación con potencial cancerígeno (Agencia de Protección Ambiental de Estados Unidos - USEPA e Agencia Internacional de Investigación sobre el Cáncer - IARC), desregulación endocrina y candidatos para sustitución, ambos de la Comunidad Europea. Se identificaron 399 ingredientes activos de pesticidas registrados en Brasil para uso agrícola, excluyéndose los microbiológicos y agentes biológicos de control. De estos, no tienen autorización en Islandia 85,7%, Noruega 84,7%, Suiza 54,5%, India 52,6%, Turquía 45,6%, Israel 44,4%, Nueva Zelanda 43,4%, Japón 42,4%, Comunidad Europea 41,5%, Canadá 39,6%, China 38,6%, Chile 35,8%, México 31,6%, Australia 28,6% y Estados Unidos 25,6%. 120 ingredientes activos de pesticidas estuvieron relacionados con daños en la salud y medioambiente. Considerando los ingredientes activos de pesticidas para los cuales están disponibles datos de comercialización en el país, un 67,2% de este volumen está asociado a por lo menos una enfermedad crónica grave evaluada en ese estudio. Los resultados del presente estudio indican la necesidad de promover la transparencia de las bases de datos internacionales, en lo que respecta a las motivaciones de las respectivas decisiones regulatorias, con el fin de que los órganos reguladores brasileños reevalúen el registro de productos obsoletos, así como para fortalecer políticas públicas relacionadas con la reducción del uso de pesticidas.

Situação regulatória internacional de agrotóxicos com uso autorizado no Brasil: potencial de danos sobre a saúde e impactos ambientais / Situación regulatoria internacional de pesticidas con uso autorizado en Brasil: potencial de daños sobre la salud e impactos ambientales / International regulatory situation of pesticides authorized for use in Brazil: potential for damage to health and environmental impacts

A legislação brasileira não prevê revisão periódica do registro dos agrotóxicos e, ainda hoje, são utilizados produtos proibidos em outros países. Partindo dos ingredientes ativos de agrotóxicos registrados no país, o presente estudo investigou a situação regulatória internacional nos países-membros da Organização para a Cooperação e Desenvolvimento Econômico (OCDE), da Comunidade Europeia e BRICS. Também se buscou relacionar os principais efeitos crônicos à saúde humana e ao meio ambiente dos ingredientes ativos de agrotóxicos mais comercializados no Brasil, em listas de classificação de potencial cancerígeno (Agência de Proteção Ambiental dos Estados Unidos - USEPA e Agência Internacional de Pesquisa em Câncer - IARC), desregulação endócrina e candidatos para substituição (estes dois últimos da Comunidade Europeia). Foram identificados 399 ingredientes ativos de agrotóxicos registrados no Brasil para uso agrícola, excluindo-se os microbiológicos e agentes biológicos de controle. Destes, não têm autorização 85,7% na Islândia, 84,7% na Noruega, 54,5% na Suíça, 52,6% na Índia, 45,6% na Turquia, 44,4% em Israel, 43,4% na Nova Zelândia, 42,4% no Japão, 41,5% na Comunidade Europeia, 39,6% no Canadá, 38,6% na China, 35,8% no Chile, 31,6% no México, 28,6% na Austrália e 25,6% nos Estados Unidos. Foram relacionados a danos à saúde e ao ambiente 120 ingredientes ativos de agrotóxicos. Considerando os ingredientes ativos de agrotóxicos para os quais estão disponíveis dados de comercialização no país, 67,2% deste volume está associado a pelo menos um dano crônico grave avaliado neste estudo. Os resultados do presente estudo indicam a necessidade de promover a transparência das bases de dados internacionais, no que tange às motivações para as respectivas decisões regulatórias e os órgãos reguladores brasileiros reavaliarem o registro de produtos obsoletos, fortalecendo políticas públicas relacionadas à redução do uso de agrotóxicos.

La legislación brasileña no prevé una revisión periódica del registro de los pesticidas e incluso hoy se utilizan productos prohibidos en otros países. Partiendo de los ingredientes activos de pesticidas registrados en el país, el presente estudio investigó la situación regulatoria internacional en los siguientes países-miembros: Organización para la Cooperación y Desarrollo Económico (OCDE), Comunidad Europea, y BRICS. También se buscó relacionar los principales efectos crónicos para la salud humana y en el medio ambiente de los ingredientes activos de pesticidas más comercializados en Brasil en listas de clasificación con potencial cancerígeno (Agencia de Protección Ambiental de Estados Unidos - USEPA e Agencia Internacional de Investigación sobre el Cáncer - IARC), desregulación endocrina y candidatos para sustitución, ambos de la Comunidad Europea. Se identificaron 399 ingredientes activos de pesticidas registrados en Brasil para uso agrícola, excluyéndose los microbiológicos y agentes biológicos de control. De estos, no tienen autorización en Islandia 85,7%, Noruega 84,7%, Suiza 54,5%, India 52,6%, Turquía 45,6%, Israel 44,4%, Nueva Zelanda 43,4%, Japón 42,4%, Comunidad Europea 41,5%, Canadá 39,6%, China 38,6%, Chile 35,8%, México 31,6%, Australia 28,6% y Estados Unidos 25,6%. 120 ingredientes activos de pesticidas estuvieron relacionados con daños en la salud y medioambiente. Considerando los ingredientes activos de pesticidas para los cuales están disponibles datos de comercialización en el país, un 67,2% de este volumen está asociado a por lo menos una enfermedad crónica grave evaluada en ese estudio. Los resultados del presente estudio indican la necesidad de promover la transparencia de las bases de datos internacionales, en lo que respecta a las motivaciones de las respectivas decisiones regulatorias, con el fin de que los órganos reguladores brasileños reevalúen el registro de productos obsoletos, así como para fortalecer políticas públicas relacionadas con la reducción del uso de pesticidas.

The Brazilian legislation does not provide for a periodic review of the registration of pesticides and, even nowadays, products banned in other countries are still used. Based on the pesticide active substances registered in the country, the present study investigated the international regulatory situation in the following member countries: Organization for Economic Co-operation and Development (OECD), European Community, and the BRICS (Brazil, Russia, India, China, and South Africa). Moreover, we sought to relate the main chronic effects to human health and the environment of the most commercialized pesticide active substances in Brazil in lists of classification of carcinogenic potential (US Environmental Protection Agency - USEPA and International Agency for Research on Cancer - IARC), endocrine disruption, and candidates for substitution, both from the European Community. A total of 399 pesticide active substances registered in Brazil for agricultural use were identified, excluding microbiological and biological control agents. Of these, the percentage of unauthorized pesticide active substances according to countries is as follows: 85.7% in Iceland; 84.7% in Norway; 54.5% in Switzerland; 52.6% in India; 45.6% in Turkey; 44.4% in Israel; 43.4% in New Zealand; 42.4% in Japan; 41.5% in the European Community; 39.6% in Canada; 38.6% in China; 35.8% in Chile; 31.6% in Mexico; 28.6% in Australia; and 25.6% in the United States. 120 pesticide active substances were related to damage to health and the environment. Considering the pesticide active substances for which commercialization data are available in the country, 67.2% of this volume is associated with at least one serious chronic damage assessed in this study. The results of the present study indicate the need for promoting transparency of international databases, regarding the motivations of the respective regulatory decisions and the Brazilian regulatory bodies to reevaluate the registration of obsolete products and to strengthen public policies related to the reduction of the use of pesticides.

STOP-Bang and NoSAS questionnaires as a screening tool for OSA: which one is the best choice?

INTRODUCTION: Currently there has been significant growth in the number of patients with suspected obstructive sleep apnea (OSA) referred to sleep clinics. In this sense, screening and stratification methods of the severity of this pathology have become increasingly relevant. OBJECTIVE: To evaluate the performance of the NoSAS and STOP-Bang scores in the screening of OSA in a sleep clinic. METHODS: Prospectively, for 12 months, all patients referred by primary care physicians to our sleep unit for clinical evaluation and who underwent in-lab polysomnography (PSG), also completed the NoSAS score (Neck circumference, Obesity, Snoring, Age, Sex) and STOP-Bang (Snoring, Tiredness, Observed apnea, Pressure (high blood), BMI, Age, Neck circumference, Gender). A ROC (receiver operating characteristic) analysis was used to find the scores that simultaneously maximize sensitivity and specificity for each diagnosis. RESULTS: Of the 294 individuals included, 84% had OSA, of which 28.8% were mild, 34.8% moderate, and 36.4% were severe. USING THE NOSAS SCORE FOR PREDICTING OSA, MODERATE TO SEVERE OSA, AND SEVERE OSA, THE ROC AREA WAS: 0.770 (95% CI: 0.703-0.837), p<0.001, sensitivity of 57.5%, and specificity of 83.0% for a score of 12; 0.746 (95% CI: 0.691-0.802), p<0.001, sensitivity of 68.2% and specificity of 75.4% for a score of 13; 0.686 (95% CI: 0.622-0.749), p<0.001, sensitivity of 71.1% and specificity of 58.3% for a score of 13, respectively. USING THE STOP-BANG SCORE FOR PREDICTING OSA, MODERATE TO SEVERE OSA, AND SEVERE OSA, THE ROC AREA WAS: 0.862 (95% CI: 0.808-0.916), p<0.001, sensitivity of 68.4% and specificity of 85.1% for a score of 5; 0.813 (95% CI: 0.756-0.861), p<0.001, sensitivity of 77.3% and specificity of 66.1% for a score of 5; 0.787 (95% CI: 0.732-0.841), p<0.001, sensitivity of 70.0% and specificity of 79.9% for a score of 6, respectively. CONCLUSIONS: The ROC area was consistently high for both scores confirming the diagnostic ability of the NoSAS and STOP-Bang questionnaires for all OSA severities. Thus, our results suggest that these questionnaires may be a powerful tool for the screening and stratification of patients in the diagnosis of OSA. Overall, the diagnostic ability of the STOP-Bang was higher than the NoSAS.

STOP-Bang and NoSAS questionnaires as a screening tool for OSA: which one is the best choice?

SUMMARY INTRODUCTION: Currently there has been significant growth in the number of patients with suspected obstructive sleep apnea (OSA) referred to sleep clinics. In this sense, screening and stratification methods of the severity of this pathology have become increasingly relevant. OBJECTIVE: To evaluate the performance of the NoSAS and STOP-Bang scores in the screening of OSA in a sleep clinic. METHODS: Prospectively, for 12 months, all patients referred by primary care physicians to our sleep unit for clinical evaluation and who underwent in-lab polysomnography (PSG), also completed the NoSAS score (Neck circumference, Obesity, Snoring, Age, Sex) and STOP-Bang (Snoring, Tiredness, Observed apnea, Pressure (high blood), BMI, Age, Neck circumference, Gender). A ROC (receiver operating characteristic) analysis was used to find the scores that simultaneously maximize sensitivity and specificity for each diagnosis. RESULTS: Of the 294 individuals included, 84% had OSA, of which 28.8% were mild, 34.8% moderate, and 36.4% were severe. USING THE NOSAS SCORE FOR PREDICTING OSA, MODERATE TO SEVERE OSA, AND SEVERE OSA, THE ROC AREA WAS: 0.770 (95% CI: 0.703-0.837), p<0.001, sensitivity of 57.5%, and specificity of 83.0% for a score of 12; 0.746 (95% CI: 0.691-0.802), p<0.001, sensitivity of 68.2% and specificity of 75.4% for a score of 13; 0.686 (95% CI: 0.622-0.749), p<0.001, sensitivity of 71.1% and specificity of 58.3% for a score of 13, respectively. USING THE STOP-BANG SCORE FOR PREDICTING OSA, MODERATE TO SEVERE OSA, AND SEVERE OSA, THE ROC AREA WAS: 0.862 (95% CI: 0.808-0.916), p<0.001, sensitivity of 68.4% and specificity of 85.1% for a score of 5; 0.813 (95% CI: 0.756-0.861), p<0.001, sensitivity of 77.3% and specificity of 66.1% for a score of 5; 0.787 (95% CI: 0.732-0.841), p<0.001, sensitivity of 70.0% and specificity of 79.9% for a score of 6, respectively. CONCLUSIONS: The ROC area was consistently high for both scores confirming the diagnostic ability of the NoSAS and STOP-Bang questionnaires for all OSA severities. Thus, our results suggest that these questionnaires may be a powerful tool for the screening and stratification of patients in the diagnosis of OSA. Overall, the diagnostic ability of the STOP-Bang was higher than the NoSAS.

RESUMO INTRODUÇÃO: Na atualidade tem se verificado um crescimento significativo no número de doentes com suspeita de apneia obstrutiva do sono (AOS) referenciados para consulta do sono. Nesse sentido, instrumentos de rastreio e estratificação da gravidade dessa patologia têm se tornado cada vez mais relevantes. OBJETIVO: Avaliar e comparar o desempenho da escala NoSAS e Stop-Bang para o rastreio de AOS. MÉTODOS: Estudo prospectivo durante 12 meses. Avaliados todos os doentes encaminhados aos cuidados de saúde primários do centro de medicina do sono que completaram o questionário NoSAS (Neck circumference, Obesity, Snoring, Age, Sex), Stop-Bang (Snoring, Tiredness, Observed apnea, Pressure [high blood], BMI, Age, Neck circumference, Gender) e foram submetidos a polissonografia. Utilizou-se uma análise ROC (receiver operating characteristic) para encontrar as pontuações que maximizam simultaneamente a sensibilidade e especificidade para cada diagnóstico. RESULTADOS: Incluídos 294 indivíduos, 84% apresentavam AOS, sendo que em 28,8% a OAS era ligeira, 34,8% moderada e 36,4% grave. USANDO A ESCALA NOSAS PARA PREVISÃO DE AOS, AOS MODERADA A GRAVE E AOS GRAVE, A ÁREA ROC FOI: 0,770 (IC95%: 0,703-0,837), p<0,001, sensibilidade de 57,5% e especificidade de 83,0% para a pontuação 12); 0,746 (IC95%: 0,691- 0,802), p<0,001, sensibilidade de 68,2% e especificidade de 75,4% para a pontuação 13); 0,686 (IC95%: 0,622-0,749), p<0,001, sensibilidade de 71,1% e especificidade de 58,3% para a pontuação 13), respectivamente. USANDO A ESCALA STOP-BANG PARA A PREVISÃO DE AOS, AOS MODERADA A GRAVE E AOS GRAVE, A ÁREA ROC FOI: 0,862 (IC95%: 0,808-0,916), p<0,001, sensibilidade de 68,4% e especificidade de 85,1% para pontuação 5); 0,813 (IC95%: 0,756-0,861), p<0,001, sensibilidade de 77,3% e especificidade de 66,1% para a pontuação 5); 0,787 (IC95%: 0,732-0,841), p<0,001, sensibilidade de 70,0% e especificidade de 79,9% para a pontuação 6), respectivamente. CONCLUSÕES: A área ROC foi consistentemente alta para as duas escalas, confirmando a capacidade diagnóstica dos questionários NoSAS e Stop-Bang para todos os graus de gravidade de AOS. Assim, os nossos resultados sugerem que esses questionários podem ser um importante instrumento para rastreio e estratificação de doentes no diagnóstico de AOS. Globalmente, a capacidade de diagnóstico do Stop-Bang foi superior à do NoSAS.

Construction and characterization of a new TRAIL soluble form, active at picomolar concentrations.

Apoptosis induction has emerged as a treatment option for anticancer therapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a type II transmembrane protein, is a potent and specific pro-apoptotic protein ligand, which activates the extrinsic apoptosis pathway of the cell death receptors. Here we describe the construction and characterization of a new soluble TRAIL, sfTRAIL, stabilized with the trimerization Foldon domain from the Fibritin protein of the bacteriophage T4. Supernatants of 0.22 µM-filtered supernatants were produced in Vero-transduced cells with HSV1-derived viral amplicon vectors. Experiments were undertaken in two known TRAIL-sensitive (U373 and MDA.MB.231) and two TRAIL-resistant (MCF7 and A549) cell lines, to determine (i) whether the sfTRAIL protein is synthetized and, (ii) whether sfTRAIL could induce receptor-mediated apoptosis. Our results showed that sfTRAIL was able to induce apoptosis at concentrations as low as 1899.29 pg/mL (27.71 pM), independently of caspase-9 activation, and reduction in cell viability at 998.73 fM.

Use of genetically modified crops and pesticides in Brazil: growing hazards.

Genetically modified (GM) crops were officially authorized in Brazil in 2003. In this documentary study, we aimed to identify possible changes in the patterns of pesticide use after the adoption of this technology over a span of 13 years (2000 to 2012). The following variables were analyzed: Pesticide use (kg), Pesticide use per capita (kg/inhab), Pesticide and herbicide use per area (kg/ha) and productivity (kg/ha). Contrary to the initial expectations of decreasing pesticide use following the adoption of GM crops, overall pesticide use in Brazil increased 1.6-fold between the years 2000 and 2012. During the same period, pesticide use for soybean increased 3-fold. This study shows that the adoption of GM crops in Brazil has led to an increase in pesticide use with possible increases in environmental and human exposure and associated negative impacts.

Use of genetically modified crops and pesticides in Brazil: growing hazards / Uso de sementes geneticamente modificadas e agrotóxicos no Brasil: cultivando perigos

Abstract Genetically modified (GM) crops were officially authorized in Brazil in 2003. In this documentary study, we aimed to identify possible changes in the patterns of pesticide use after the adoption of this technology over a span of 13 years (2000 to 2012). The following variables were analyzed: Pesticide use (kg), Pesticide use per capita (kg/inhab), Pesticide and herbicide use per area (kg/ha) and productivity (kg/ha). Contrary to the initial expectations of decreasing pesticide use following the adoption of GM crops, overall pesticide use in Brazil increased 1.6-fold between the years 2000 and 2012. During the same period, pesticide use for soybean increased 3-fold. This study shows that the adoption of GM crops in Brazil has led to an increase in pesticide use with possible increases in environmental and human exposure and associated negative impacts.

Resumo Culturas geneticamente modificadas (GM) foram oficialmente autorizadas no Brasil em 2003. O presente estudo documental buscou identificar possíveis alterações no padrão de uso de agrotóxicos a partir da adoção dessa tecnologia, considerando um período de 13 anos (2000 a 2012). Foram avaliadas as variáveis: uso de agrotóxicos (kg), uso de agrotóxicos per capita (kg/habitante), uso de agrotóxicos e uso de herbicidas por área plantada (kg/ha) e produtividade (kg/ha). Contrariando as expectativas iniciais de diminuição do uso de agrotóxicos após a introdução de culturas GM, observou-se que o uso total de agrotóxicos no Brasil aumentou 1,6 vezes entre os anos de 2000 e 2012. No mesmo período, destacou-se o uso de agrotóxicos na cultura de soja, aumentando em mais de 3 vezes. As análises estatísticas reforçam baixa correlação entre o consumo de agrotóxicos e herbicidas e a produtividade da soja. Sugere-se que a introdução de culturas GM levou ao aumento no uso de agrotóxicos, com a possibilidade de aumento da exposição humana e ambiental e, consequentemente, aos impactos negativos associados a essas substâncias.

A economia solidária como uma forma de promoção da juventude no campo / The solidarity economy as a way to promote youth

Introdução: A Incubadora Tecnológicas de Cooperativas Sociais de Economia Solidária da UnB em parceria com a Fiocruz Brasília vem desenvolvendo um projeto de geração de trabalho e renda junto ao assentamento Cunha, na cidade Ocidental, em Goiás. Inicialmente, está sendo realizada uma atividade de inclusão digital e economia solidária. Objetivo: Refletir sobre território e resistência por meio de uma experiência com juventude rural e economia solidária. Metodologia: Foi realizada uma observação participante por meio de visita no território, com registro em diário de campo e entrevista. Resultados: Em uma visita foi possível conhecer o assentamento, e observar aspectos importantes sobre o território e participar de uma atividade formativa no Centro de Metarreciclagem em Valparaíso, em Goiás. Os jovens vivem sob a pressão e o constante risco de abandonar a comunidade e a casa dos pais pela carência de transporte coletivo, acesso aos serviços de saúde e a uma escolarização regular, além da ausência completa de atrativos culturais, possibilidades de aumentar a renda ou as oportunidades laborais e de formação. Conclusão: Este trabalho mostrase promissor como possibilidade de qualificação profissional por meio da inclusão digital e também, como perspectiva futura de melhoria tecnológica dos meios de produção e comercialização. E o fundo solidário poderá permitir aos jovens financiarem pequenos negócios para geração de renda no campo. Como é um projeto inicial, avaliações periódicas e monitoramentos de processo e resultado são necessários.

Introduction: The Technological Incubator of Social Cooperatives Solidarity Economy of UnB in partnership with Fiocruz Brasilia has de veloped a job and income generating work with the Cunha settlement in Western city, Goiás. Initially, digital inclusion and solidarity economy activitities. Objective: The aim of this work is to reflect on territory and resistance through an experience with rural youth and solidarity economy. Methods: The research was developed through the method of participatory observation, visiting the territory, diary report and interviews. Results: It was also possible to experience the settlement, observe important aspects of the territory and participate in a training activity in Recicle Centre in Valparaíso, Goiás. Young people live under pressure and at the constant risk of leaving the community and parent´s home because of scarce of public transportation, access to health services and regular education, besides the complete absence of cultural attractions, opportunities to increase income or get employed and training opportunities. Conclusion: This task showed promising as a possible qualification through digital inclusion as well as to future perspectives of technological improvement of production and trading means. And the solidarity fund could enable young people finance small businesses in order to generate income with their families in the field. Once it is an initial project, periodic assessments and monitoring of processes and results are needed.

Experienced pediatric nurses' perceptions of work-related stressors on general medical and surgical units: A qualitative study.

BACKGROUND: Experienced pediatric nurses caring for increasingly sick and vulnerable children on medical and surgical units may be at particular risk for work-related stress. In view of their positive impact on quality of care, and the fact that they are particularly difficult to retain, it is imperative to understand the work-related stressors these nurses encounter in order to develop effective organizational interventions to minimize stressors and promote retention. OBJECTIVE: To explore experienced pediatric nurses' perceptions of work-related stressors in medical and surgical units. DESIGN: Qualitative descriptive design with semi-structured interviews. SETTING: Medical and surgical units at a quaternary care pediatric hospital in Montreal, Canada. PARTICIPANTS: Nurses recognized as experienced by the nursing leadership team as reflected by having been 'in charge' of the unit, or having trained junior staff, and who had been practicing full-time for three years or more on a general medical or surgical pediatric unit were eligible to participate. Purposive sampling was used, and nurses recruited until data saturation was reached (n=12). There were no refusals to participate. METHODS: Semi-structured interviews were conducted between August and December 2013. RESULTS: Nurses described a strong sense of responsibility for providing excellent patient care, and identified stressor that negatively impacted their ability to do so. Stressors are reflected in three themes: (1) "The kids are getting sicker and sicker": Difficulty ensuring excellent patient care to an increasingly vulnerable population, (2) Feeling powerless to provide quality care, and (3) Being a "Jack-of-all-trades": Struggling with competing demands. CONCLUSION: Experienced pediatric nurses felt powerless to provide quality care to an increasingly acute and vulnerable population. Dealing with multiple and diverse responsibilities, and limited resources and support, were important stressors. Nurse Managers and educators could mitigate stressors and improve retention of experienced pediatric nurses by offering targeted continuing education to those newly responsible for additional roles, and building supportive working environments that encourage collaboration and empower experienced nurses.

In vitro and in vivo activity of a new unsymmetrical dinuclear copper complex containing a derivative ligand of 1,4,7-triazacyclononane: catalytic promiscuity of [Cu2(L)Cl3].

Here we present the synthesis of the dinuclear complex [Cu(II)2(L)Cl3] (1), where L is the deprotonated form of the 3-[(4,7-diisopropyl-1,4,7-triazacyclononan-1-yl)methyl]-2-hydroxy-5-methylbenzaldehyde ligand. The complex was characterized by single crystal X-ray diffraction, potentiometric titration, mass spectrometry, electrochemical and magnetic measurements, EPR, UV-Vis and IR. Complex 1 is able to increase the hydrolysis rate of the diester bis-(2,4-dinitrophenyl)phosphate (2,4-BDNPP) by a factor of 2700, and also to promote the plasmidial DNA cleavage at pH 6 and to inhibit the formazan chromophore formation in redox processes at pH 7. Using Saccharomyces cerevisiae (BY4741) as a eukaryotic cellular model, we observed that 1 presents reduced cytotoxicity. In addition, treatment of wild-type and mutant cells lacking Cu/Zn-superoxide dismutase (Sod1) and cytoplasmic catalase (Ctt1) with 1 promotes increased survival after H2O2 or menadione (O2˙(-) generator) stress, indicating that 1 might act as a Sod1 and Ctt1 mimetic. Considered together, these results support considerations regarding the dynamic behaviour of an unsymmetrical dinuclear copper(II) complex in solid state and in aqueous pH-dependent solution.

Synthesis, magnetostructural correlation, and catalytic promiscuity of unsymmetric dinuclear copper(II) complexes: models for catechol oxidases and hydrolases.

Herein, we report the synthesis and characterization, through elemental analysis, electronic spectroscopy, electrochemistry, potentiometric titration, electron paramagnetic resonance, and magnetochemistry, of two dinuclear copper(II) complexes, using the unsymmetrical ligands N',N',N-tris(2-pyridylmethyl)-N-(2-hydroxy-3,5-di-tert-butylbenzyl)-1,3-propanediamin-2-ol (L1) and N',N'-bis(2-pyridylmethyl)-N,N-(2-hydroxybenzyl)(2-hydroxy-3,5-di-tert-butylbenzyl)-1,3-propanediamin-2-ol (L2). The structures of the complexes [Cu(2)(L1)(µ-OAc)](ClO(4))(2)·(CH(3))(2)CHOH (1) and [Cu(2)(L2)(µ-OAc)](ClO(4))·H(2)O·(CH(3))(2)CHOH (2) were determined by X-ray crystallography. The complex [Cu(2)(L3)(µ-OAc)](2+) [3; L3 = N-(2-hydroxybenzyl)-N',N',N-tris(2-pyridylmethyl)-1,3-propanediamin-2-ol] was included in this study for comparison purposes only (Neves et al. Inorg. Chim. Acta2005, 358, 1807-1822). Magnetic data show that the Cu(II) centers in 1 and 2 are antiferromagnetically coupled and that the difference in the exchange coupling J found for these complexes (J = -4.3 cm(-1) for 1 and J = -40.0 cm(-1) for 2) is a function of the Cu-O-Cu bridging angle. In addition, 1 and 2 were tested as catalysts in the oxidation of the model substrate 3,5-di-tert-butylcatechol and can be considered as functional models for catechol oxidase. Because these complexes possess labile sites in their structures and in solution they have a potential nucleophile constituted by a terminal Cu(II)-bound hydroxo group, their activity toward hydrolysis of the model substrate 2,4-bis(dinitrophenyl)phosphate and DNA was also investigated. Double electrophilic activation of the phosphodiester by monodentate coordination to the Cu(II) center that contains the phenol group with tert-butyl substituents and hydrogen bonding of the protonated phenol with the phosphate O atom are proposed to increase the hydrolase activity (K(ass.) and k(cat.)) of 1 and 2 in comparison with that found for complex 3. In fact, complexes 1 and 2 show both oxidoreductase and hydrolase/nuclease activities and can thus be regarded as man-made models for studying catalytic promiscuity.

Avaliação de programas sociais de mensuração de resultados para uma abordagem construtivista / Evaluation of social programs from mensuration of results towards a constructivist approach

O artigo discute duas formas de avaliar um programa social. No métodoconvencional busca-se verificar o valor e/ou o mérito de um programa, com a finalidadede responder às indagações dos financiadores ou executores, levantando dadosquantificáveis segundo uma abordagem positivista. Já na perspectiva construtivista,propõe-se avaliar o impacto dos programas sociais em seu contexto de implantação. Essemétodo mostra-se pertinente às necessidades da Psicologia Social, já que mais do queobter um estudo das relações sociais, considera a subjetividade dos sujeitos pesquisados,como, por exemplo, na sua capacidade de reordenamento diante das intervenções quelhe são dirigidas. Com isso busca-se intervir nas formas como essas relações acontecem,podendo contribuir, com as políticas sociais, uma vez que está em construção uma novaforma de se fazer política, na qual o protagonismo e o controle social tornam-seelementos indispensáveis(AU)

The paper makes a comparison between two evaluative approaches. In a moreconventional way, the goal is to verify the value of a program according to the interestsof its sponsors. In a positivist view, the evaluation is carried out only with the basis ofquantifiable data. Differently, the constructivist approach seeks to evaluate socialprograms in their context of application. It is a method more useful for Social Psychologybecause it focus on social relations as well as in the subjectivities of those involved in the research. It considers that the subjects are capable of reorganize themselves under theimpact of the social interventions. The constructivist approach aims to intervene in theserelations and to contribute for social policies, pointing out to a new way of doing politics,with the basis on social control and participation of the involved social actors(AU)

Diagnóstico ecocardiográfico de transposiçäo das grandes artérias associada à drenagem anômala de veias pulmonares / Echocardiographic diagnosis of transposition of the great arteries associated with anomalous pulmonary venous connection

We report 2 cases of transposition of the great arteries associated with anomalous pulmonary venous connection emphasizing the clinical findings, the diagnosis, and the evolution of the association. One of the patients had the anomalous pulmonary venous connection in its total infradiaphragmatic form, in the portal system, and the other patient had a partial form, in which an anomalous connection of the left superior lobar vein with the innominate vein existed. At the time of hospital admission, the patients had cyanosis and respiratory distress with clinical findings suggesting transposition of the great arteries. The diagnosis in 1 of the cases, in which the anomalous connection was partial, was established only with echocardiography, without invasive procedures that would represent risk for the patient; in the other case, in which the anomalous connection was total, the malformation was only evidenced with catheterization. The patients underwent surgery for anatomical correction of the heart disease. Only 1 patient had a good outcome