Investigation of Ehrlich ascites tumor cell death mechanisms induced by Synadenium umbellatum Pax.

AbstractEthnopharmacological relevanceSynadenium umbellatum Pax. is widely found in South America and empirically used in Brazil for the treatment of several diseases, mainly cancer. The aim of the study was to investigate cell death mechanisms induced by Synadenium umbellatum Pax. using Ehrlich ascites tumor (EAT) cells, as well as the myelotoxicity potential of this plant.Materials and methodsS. umbellatum cytotoxicity was evaluated in EAT cells by trypan blue exclusion and MTT reduction test and the mechanisms involved in EAT cell death were investigated by light and fluorescence microscopy, flow cytometry and immunocytochemistry. Investigation of S. umbellatum myelotoxicity was performed by clonogenic assay of colony forming unit- granulocyte macrophage (CFU-GM).Results and ConclusionOur results demonstrated that S. umbellatum decreased the viability of EAT cells using both methods. Morphological analyses revealed that S. umbellatum-treatment induced EAT cell death by apoptotic pathway. We demonstrated the occurrence of reactive oxygen species (ROS) overgeneration, increased intracellular Ca2+ concentration, alteration in mitochondrial membrane potential, phosphatydylserine externalization, and activation of caspases 3, 8, and 9. However, S. umbellatum produced myelotoxicity in bone marrow cells in a concentration-dependent manner. In comparison to EAT cells, the effects of S. umbellatum in bone marrow cells were 8-fold lower. Taken together, our results showed that S. umbellatum induced apoptosis in EAT cells at several levels and seems more toxic to tumor cells than to normal bone marrow cells

A assistência na Saúde da Família sob a perspectiva dos usuários

This descriptive exploratory study analyzed user satisfaction with the care received at a Family Health Unit in Ribeirão Preto, Brazil. In total, 40 users from families registered in the FHU were selected, using key informants and the snowball sampling technique, and interviewed. Thematic content analysis was used to analyze the empirical material. Interviewees were mostly female, over 50 years, resident in the catchment area of the unit for 10-30 years, had incomplete primary education and also did not perform work outside the home. The analysis identified three themes: access, team-user interaction and organization of work in the FHU. The subjects of this study expressed satisfaction with the accessibility provided together with the caring attention given to them, marked by a team-user interaction that takes place in a friendly and patience manner. Although not totally satisfied, the majority of users would recommend the health service to someone due to its quality.Este estudio exploratorio y descriptivo analizó la satisfacción del usuario en lo que se refiere a la atención recibida en una unidad de Salud de la Familia(USF) en Ribeirao Preto-SP, Brasil. Fueron entrevistados 40 usuarios de familias registradas por la USF, seleccionadas por informantes clave y muestreo por bola de nieve. El análisis temático de contenido se utilizó para analizar el material empírico. Los entrevistados son mayoritariamente mujeres, con más de 50 años, residentes en el área de alcance de la unidad, entre 10 y 30 años, tienen enseñanza primaria incompleta y no ejercían trabajo fuera del domicilio. El análisis identificó tres temas: acceso, interacción equipo-usuario y organización del trabajo en la USF. Los sujetos del estudio expresaron satisfacción con la accesibilidad desde que vinculada a la atención cuidadosa que recibían, marcada por una interacción equipo-usuario amigable y paciente. A pesar de que no están totalmente satisfechos, la mayoría de los usuarios indicaría este servicio por su calidad.Analisou-se satisfação do usuário quanto ao atendimento em uma Unidade de Saúde da Família (USF) em Ribeirão Preto, SP, Brasil. É um estudo exploratório descritivo. Foram entrevisados 40 usuários de famílias cadastradas pela USF, selecionados a partir de informantes chave e da técnica snowball para amostragem. Para análise do material empírico, utilizou-se análise de conteúdo na modalidade temática. Os entrevistados são majoritariamente mulheres, acima de 50 anos, residentes na área de abrangência da unidade, de 10-30 anos, possuíam ensino fundamental incompleto e também não exerciam trabalho fora do domicílio. A análise identificou três temas: acesso, interação equipe/usuário e organização do trabalho na USF. Os sujeitos deste estudo expressam satisfação com a acessibilidade desde que aliada à atenção cuidadosa que lhes é dispensada, marcada por interação equipe/usuário que se produz de forma amigável e pacienciosa. Embora não totalmente satisfeitos, a maioria dos usuários indicaria esse serviço de saúde a alguém, por sua qualidade

‘People lie’: overcoming obstacles to incorporate social science research to biodiversity conservation

Mesmo com o reconhecimento da importância da interdisciplinaridade na conservação da biodiversidade, ainda há resistência em incorporar a pesquisa em ciências sociais (PCS) ao pensamento e à prática conservacionista. As razões para tal resistência podem ser resumidas em três afirmações gerais ainda comumente atribuídas à PCS: 'tem pouca utilidade' e 'menos rigor metodológico' quando comparada à pesquisa em ciências naturais e, sobretudo, é pouco confiável porque 'as pessoas mentem'. Neste ensaio, desenvolvido a partir da experiência dos participantes de uma comunidade de prática, formada por profissionais de diversas áreas e setores relacionados à conservação, e das discussões geradas nesse espaço de aprendizado coletivo, abordamos as limitações e os equívocos por trás das afirmações acima. A PCS não é menos útil na conservação e nem tem menos rigor metodológico do que a pesquisa em ciências naturais, e quando as pessoas mentem para o pesquisador o problema não está na pesquisa em si, mas na relação entre sujeito e pesquisador. Argumentamos que à medida que os conservacionistas se familiarizam com a PCS e que os princípios de equidade e justiça são incorporados aos valores e objetivos da conservação, a importância e necessidade da PCS na conservação tornam-se óbvias, e a falta de confiança entre pesquisador e sujeitos deixa de ser uma preocupação significativa. Capacitar, integrar e apoiar são nossas recomendações básicas para pesquisadores, educadores, gestores e tomadores de decisão nas áreas de conservação, ensino, publicação e financiamento, para que a PCS cumpra plenamente seu papel na conservação.Despite the acknowledged importance of interdisciplinarity in biodiversity conservation, there is still resistance to incorporate social science research (SSR) to both conservationist thinking and practice. The reasons for such a resistance can be summarized in three general statements still commonly attributed to SSR, namely: it is of 'little use' and it has 'less methodological rigor' than research in the natural sciences and, above all, it is unreliable because 'people lie'. The current essay was developed based on the experience of participants of a community of practice (formed by professionals from different fields and sectors  associated with conservation), as well as on discussions held in this space of collective learning. It addresses the limitations and misconceptions behind the aforementioned statements. SSR is not less useful in conservation and not less methodologically rigorous than research conducted in the natural sciences. When researchers are lied to, the problem does not lie on the research itself, but on the subject-researcher relationship. We herein argue that as conservationists become more familiar with SSR, and as principles like equity and justice are incorporated to conservation values and goals, both the importance and need of SSR in conservation become obvious, making the lack of trust between researcher and subjects no longer a significant concern. Increasing capacity, integrating and supporting are our basic recommendations for researchers, educators, managers and decision-makers in the conservation, teaching, publishing and funding fields, so that SSR can fully fulfill its role in conservation

IL-17 Produced during Trypanosoma cruzi Infection Plays a Central Role in Regulating Parasite-Induced Myocarditis

Chagas disease is caused by the intracellular parasite Trypanosoma cruzi. This infection has been considered one of the most neglected diseases and affects several million people in the Central and South America. Around 30% of the infected patients develop digestive and cardiac forms of the disease. Most patients are diagnosed during the chronic phase, when the treatment is not effective. Here, we showed by the first time that IL-17 is produced during experimental T. cruzi infection and that it plays a significant role in host defense, modulating parasite-induced myocarditis. Applying this analysis to humans could be of great value in unraveling the elements involved in the pathogenesis of chagasic cardiopathy and could be used in the development of alternative therapies to reduce morbidity during the chronic phase of the disease, as well as clinical markers of disease progression. The understanding of these aspects of disease may be helpful in reducing the disability-adjusted life years (DALYs) and costs to the public health service in developing countries

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODErn), to generate cause fractions and cause specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NC Ds) comprised the greatest fraction of deaths, contributing to 73.4% (95% uncertainty interval [UI] 72.5-74.1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 186% (17.9-19.6), and injuries 8.0% (7.7-8.2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22.7% (21.5-23.9), representing an additional 7.61 million (7. 20-8.01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7.9% (7.08.8). The number of deaths for CMNN causes decreased by 222% (20.0-24.0) and the death rate by 31.8% (30.1-33.3). Total deaths from injuries increased by 2.3% (0-5-4-0) between 2007 and 2017, and the death rate from injuries decreased by 13.7% (12.2-15.1) to 57.9 deaths (55.9-59.2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000-289 000) globally in 2007 to 352 000 (334 000-363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118.0% (88.8-148.6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36.4% (32.2-40.6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33.6% (31.2-36.1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respirator}, infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990 neonatal disorders, lower respiratory infections, and diarrhoeal diseases were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.Peer reviewe

Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

Background: Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10–24 years during the past three decades. Methods: Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100 000 population by sex, age group (10–14, 15–19, and 20–24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We report percentage changes in deaths and DALYs between 1990 and 2019. Findings: In 2019, 369 061 deaths (of which 214 337 [58%] were transport related) and 31·1 million DALYs (of which 16·2 million [52%] were transport related) among adolescents aged 10–24 years were caused by transport and unintentional injuries combined. If compared with other causes, transport and unintentional injuries combined accounted for 25% of deaths and 14% of DALYs in 2019, and showed little improvement from 1990 when such injuries accounted for 26% of adolescent deaths and 17% of adolescent DALYs. Throughout adolescence, transport and unintentional injury fatality rates increased by age group. The unintentional injury burden was higher among males than females for all injury types, except for injuries related to fire, heat, and hot substances, or to adverse effects of medical treatment. From 1990 to 2019, global mortality rates declined by 34·4% (from 17·5 to 11·5 per 100 000) for transport injuries, and by 47·7% (from 15·9 to 8·3 per 100 000) for unintentional injuries. However, in low-SDI nations the absolute number of deaths increased (by 80·5% to 42 774 for transport injuries and by 39·4% to 31 961 for unintentional injuries). In the high-SDI quintile in 2010–19, the rate per 100 000 of transport injury DALYs was reduced by 16·7%, from 838 in 2010 to 699 in 2019. This was a substantially slower pace of reduction compared with the 48·5% reduction between 1990 and 2010, from 1626 per 100 000 in 1990 to 838 per 100 000 in 2010. Between 2010 and 2019, the rate of unintentional injury DALYs per 100 000 also remained largely unchanged in high-SDI countries (555 in 2010 vs 554 in 2019; 0·2% reduction). The number and rate of adolescent deaths and DALYs owing to environmental heat and cold exposure increased for the high-SDI quintile during 2010–19. Interpretation: As other causes of mortality are addressed, inadequate progress in reducing transport and unintentional injury mortality as a proportion of adolescent deaths becomes apparent. The relative shift in the burden of injury from high-SDI countries to low and low–middle-SDI countries necessitates focused action, including global donor, government, and industry investment in injury prevention. The persisting burden of DALYs related to transport and unintentional injuries indicates a need to prioritise innovative measures for the primary prevention of adolescent injury. Funding: Bill & Melinda Gates Foundation