Imidazole derivatives as promising agents for the treatment of Chagas disease

More than 100 years later after being firstly described, Chagas disease remains endemic in 21 Latin American countries and has spread to other continents. Indeed, this disease, caused by the protozoan parasite Trypanosoma cruzi, is no longer just a problem for the American continent but has become a global health threat. Current therapies, nifurtimox and benznidazole (Bz), are far from being adequate due to undesirable effects and their lack of efficacy in the chronic phases of the disease. In this work, we present an in-depth phenotypical evaluation in T.cruzi of a new class of imidazole compounds, discovered in a previous phenotypic screening against different trypanosomatids and designed as potential inhibitors of cAMP phosphodiesterases (PDEs). The confirmation of several activities similar or superior to Bz prompted a synthesis program of hit optimization and extended SAR, aimed at improving drug-like properties such as aqueous solubility, resulting in additional hits with IC50 similar to Bz. The cellular effects of one representative hit, compound 9, on bloodstream trypomastigotes were further investigated. Transmission electron microscopy revealed cellular changes, after just 2 h of incubation with the IC50 concentration, that were consistent with induced autophagy and osmotic stress - mechanisms previously linked to cAMP signaling. Compound 9 induced highly significant increases in both cellular and medium cAMP, confirming that inhibition of T.cruzi PDE(s) is part of its mechanism of action. The potent and selective activity of this imidazole-based PDE inhibitor class against T.cruzi constitutes a successful repurposing of research into inhibitors of mammalian PDEs

Narrar histórias para se constituir educador ambiental pela pesquisa

Research, along with narrative, is presented as an educational principle which can transform the reality in environmental teacher education. The research exercise described in this paper was developed by a discussion group - GDP - about research in environmental teacher education at the IV EPEA, a seminar on research in Environmental Education. We believe that narrative may transform environmental educators in their learning process.Apresenta-se a pesquisa como princípio educativo agregada à narrativa como elemento transformador da realidade da formação de educadores ambientais. O exercício de pesquisa apresentado foi desenvolvido no grupo de discussão - GDP - sobre pesquisa na formação de educadores ambientais no IV EPEA - Encontro de Pesquisa em Educação Ambiental. Aposta-se na possibilidade da narrativa na constituição transformadora de educadores ambientais

Trombose venosa profunda: aspectos epidemiológicos, fisiopatológicos e manejo terapêutico

A Trombose Venosa Profunda (TVP) é uma condição médica grave caracterizada pela formação de um coágulo sanguíneo dentro das veias profundas do corpo, principalmente nas pernas. Quanto à epidemiologia, trata-se de uma doença comum em todo o mundo, afetando entre 2,5% a 5% da população. A prevalência da TVP aumenta com a idade e é maior em homens do que em mulheres. A fisiopatologia da TVP envolve a formação de coágulos sanguíneos nas veias profundas das pernas, o que pode ocorrer devido a uma variedade de fatores, incluindo imobilização prolongada, tabagismo, cirurgias, trauma, câncer, uso de contraceptivos orais, gravidez e pós-parto, fatores genéticos e obesidade. Quanto às manifestações clínicas, destacam-se dor, inchaço e vermelhidão nas pernas afetadas, bem como sensação de calor na pele sobre a veia afetada. No entanto, muitos casos de TVP são assintomáticos, o que torna o diagnóstico precoce desafiador. O diagnóstico da TVP envolve avaliação clínica, exames laboratoriais, exames de imagem, como ultrassonografia doppler, que podem detectar a presença de coágulos sanguíneos nas veias profundas das pernas. Já a abordagem terapêutica envolve o uso de medicamentos como anticoagulantes, que ajudam a prevenir a formação de novos coágulos sanguíneos e reduzem o risco de complicações graves. Em alguns casos, a remoção do coágulo pode ser necessária para prevenir complicações. A prevenção da TVP também é importante, especialmente em pessoas com fatores de risco, e pode envolver a mudança de estilo de vida e o uso de medicamentos preventivos

Aspectos metodológicos e desafios da Coorte On-line Comportamento Alimentar e Saúde Mental (COCASa) de docentes e discentes universitários durante a pandemia da COVID-19

O distanciamento social adotado para controle da COVID-19 obrigou Instituições de Ensino Superior (IES) a aderirem a novas estratégias para realização das atividades acadêmicas e muitas pesquisas passaram a ser realizadas em ambientes virtuais. O objetivo deste artigo é descrever os aspectos metodológicos e principais desafios enfrentados para a execução do projeto COCASa, um estudo de coorte on-line sobre comportamento alimentar e saúde mental de docentes e discentes de IES do Brasil. O estudo foi iniciado em julho de 2020 e acompanhará os participantes por dois anos. Adotou-se amostragem não probabilística estratificada proporcional com a utilização de escalas, de inquérito alimentar e de questões estruturadas elaboradas pela equipe do projeto. Entre os participantes do baseline, 4.074 discentes e 2.210 docentes iniciaram o questionário e, respectivamente, 76,8% e 85,1% finalizaram o preenchimento. Em ambos os grupos, a maior participação foi de mulheres (docentes: 66,7% e discentes: 76,2%) e residentes nas regiões Nordeste (docentes: 37% e discentes: 50,9%) e Sul (docentes: 27,1% e discentes: 22,5%) do Brasil. A pesquisa on-line amplia a possibilidade de recrutamento de participantes e alcança limites territoriais com menor demanda por financiamento. Durante a pandemia da COVID-19, o uso do ambiente virtual tornou-se uma estratégia viável e acessível para a manutenção das atividades de pesquisa, configurando-se como uma provável tendência a ser adotada pela comunidade científica

Anoxia- and hypoxia-induced expression of LDH-A* in the Amazon Oscar, Astronotus crassipinis

Adaptation or acclimation to hypoxia occurs via the modulation of physiologically relevant genes, such as erythropoietin, transferrin, vascular endothelial growth factor, phosphofructokinase and lactate dehydrogenase A. In the present study, we have cloned, sequenced and examined the modulation of the LDH-A gene after an Amazonian fish species, Astronotus crassipinis (the Oscar), was exposed to hypoxia and anoxia. In earlier studies, we have discovered that adults of this species are extremely tolerant to hypoxia and anoxia, while the juveniles are less tolerant. Exposure of juveniles to acute hypoxia and anoxia resulted in increased LDH-A gene expression in skeletal and cardiac muscles. When exposed to graded hypoxia juveniles show decreased LDH-A expression. In adults, the levels of LDH-A mRNA did not increase in hypoxic or anoxic conditions. Our results demonstrate that, when given time for acclimation, fish at different life-stages are able to respond differently to survive hypoxic episodes

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

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 understanding 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,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 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 underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities 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 organism 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 neglected 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 lost

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 understanding 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,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 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 underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities 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 organism 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 neglected 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 lost

Evaluation and Psychological Intervention in Pregnancy loss

A perda gestacional constitui um acontecimento potencialmente traumático, devido ao seu carácter normalmente inesperado e imprevisível. Ao processo de luto subsequente a este evento estão subjacentes algumas tarefas (nomeadamente, a aceitação da morte e a expressão emocional da dor que lhe está associada), existindo um conjunto variado de manifestações emocionais, cognitivas, comportamentais e fisiológicas que constituem reacções esperadas face às circunstâncias. Embora apenas uma minoria dos casais que se confronta com uma perda gestacional desenvolva psicossintomatologia clinicamente significativa, os profissionais de saúde mental podem ter um papel relevante na promoção da aceitação da perda e da expressão emocional, bem como na integração deste acontecimento. O presente trabalho debruça-se sobre as especificidades da vivência do luto perante uma situação de perda gestacional, salientando os diversos parâmetros que devem ser alvo de avaliação clínica cuidada e propondo estratégias terapêuticas específicas para cada um dos principais objectivos da intervenção clínica.Pregnancy loss, due to frequently being unexpected and unpredictable, is a potentially traumatic event. The subsequent grief process is characterized by some tasks (namely, accepting the death and ex-pressing the associated feelings), and there is a group of emotional, cognitive, behavioral and physiologic symptoms which are expected to occur, considering the circumstances. Although only a small percentage of couples dealing with a pregnancy loss will show clinically significant psychosymptomatology, mental he-alth professionals may have a relevant role in promoting the acceptance of the loss and the emotional ex-pression, as well as the integration of this event. The present work focuses the specificities of grief experi-ence due to pregnancy loss, pointing out the factors which should be carefully assessed and presenting spe-cific therapeutic strategies for each of the main goals of clinical intervention