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    Esteroides anabólicos androgênicos: uma revisão cronológica

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    A crescente utilização de esteroides anabólicos androgênicos tem se tornado uma preocupação social de progressão considerável na atualidade. Embasando-se nas propriedades hormonais, nos prováveis efeitos deletérios e nos esteroides anabólicos androgênicos mais usuais, o presente estudo científico, através do método de revisão de literatura narrativa, possibilita historiar as atribuições e propriedades dos esteroides anabólicos androgênicos de modo abrangente. As primeiras revelações da pesquisa contribuem para transmitir os interesses para as primeiras pesquisas e experimentações, cientificas ou não, até a idealização dos esteroides anabólicos androgênicos. Conta-se, então, através da datação de fatos, o progresso gradual dos esteroides anabólicos androgênicos: descoberta, isolamento, síntese, propalação, distribuição, comercialização até a indiscriminação de seu uso. Isto posto, é possível o esclarecimento das motivações do uso de esteroides anabólicos androgênicos no meio desportivo, bem como o conhecimento das propriedades fisiológicas que suscitam a alta procura destes sintéticos. A pesquisa ainda disponibiliza evidências sobre os índices de utilização de usuários recreacionais e competitivos, sendo esta última classe regularizada e fiscalizada por órgãos de influência mundial no combate ao uso de substâncias exógenas, independente do propósito (melhora física, melhora no desempenho ou performance) valendo-se de medidas corretivas aos atletas que fogem à regra. Quando, por fim, os efeitos imediatos dos esteroides anabólicos androgênicos colocados à prova por um grupo de pesquisadores que contestam a eficácia de um dos experimentos mais importantes da história da humanidade. Pretende-se, desta maneira, alcançar todas as classes populacionais, proporcionando-as conhecimento acerca dos esteroides anabólicos androgênicos, a partir de uma análise ampla proporcionada pelo histórico cronológico e descritivo sobre essas drogas, para alertá-las quanto as adversidades ocasionadas devido sua ministração através de campanhas sociais e educacionais

    Estudo da atividade antileishmanial de um novo sal orgânico derivado de triazol em leishmania amazonensis

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    Leishmaniasis is an infectious disease that is difficult to control and presents itself in three clinical forms: cutaneous, mucocutaneous and visceral leishmaniasis, caused by more than 20 species of parasites of the genus Leishmania spp., transmitted by the insect vector, the sand fly. Current chemotherapy for leishmaniasis faces significant limitations due to high toxicity, prolonged treatment regimens and increased parasite resistance, highlighting the urgent need for new treatment strategies. This study aimed to evaluate the in vitro activity of triazole derivatives against promastigotes and amastigotes of L. amazonensis, as well as its cytotoxicity in murine macrophages. In addition to investigate the mechanism of parasite killing. antipromastigote activity and cytotoxicity in peritoneal macrophages were determined by the colorimetric MTT method after 72 hours of treatment. The anti-amastigote effect was evaluated in macrophages infected with L. amazonensis after 72 hours of incubation, stained with Giemsa and counted by optical microscopy. The tests for analysis of the mechanism of action were performed using different biochemical and cellular indicators of cell death parameters, by fluorimetry and flow cytometry. Additionally, the ultrastructure and morphology of promastigotes treated with TZDS were analyzed by electron microscopy. The results found highlighted the importance of triazole salts, since the neutral form did not show inhibition of parasite growth. However, the triazole-derived salt demonstrated a promising selective index (SI = 34.28) and antileishmanial activity (IC50 = 0.13 μM and IC50 = 2.06 μM against promastigote and amastigote forms, respectively), proving to be more active than miltefosine, the standard drug. Regarding the TZDS mode of action, this compound induced significant mitochondrial alterations in the parasite, characterized by an increase in mitochondrial membrane potential (ΔΨm), elevated levels of total and mitochondrial Reactive Oxygen Species (ROS), and accumulation of lipid bodies in the cytoplasm. Treatment with triazole salt also produced several ultrastructural, biochemical, and cellular alterations in the promastigotes, consistent with apoptosislike cell death, including cell shrinkage and reduction in length, as well as exposure of phosphatidylserine in the outer leaflet of the plasma membrane and marked cell cycle arrest, in addition to DNA fragmentation. Despite the positive MDC (monodansylcadaverine) and the presence of membrane-bound vacuoles resembling autophagosomal structures observed by TEM analysis, autophagy is not a predominant process, with severe mitochondrial damage emerging as the primary event leading to parasite death. These findings demonstrate the promising antileishmanial potential of the triazole-derived salt, with its effect on multiple targets in L. amazonensis cells. Furthermore, the association of the active compound with miltefosine showed an additive effect in the treatment of macrophages infected by L. amazonensis. Overall, these results highlight the therapeutic potential of the evaluated salt and support further studies to evaluate its in vivo efficacy in a murine model of cutaneous leishmaniasis.As leishmanioses são doenças infecciosas de difícil controle e se apresentam em três formas clínicas: leishmaniose cutânea, mucocutânea e visceral, causadas por mais de 20 espécies de parasitos do gênero Leishmania spp., sendo transmitidos pelo inseto vetor, flebotomíneo. A quimioterapia atual para leishmaniose enfrenta limitações significativas devido à alta toxicidade, regimes de tratamento prolongados e aumento da resistência do parasita, destacando a necessidade urgente de novas estratégias de tratamentos. Este estudo teve como objetivo avaliar a atividade in vitro do sal de derivados de triazol contra promastigotas e amastigotas de L. amazonensis, bem como sua citotoxicidade em macrófagos murinos. Além disso, investigar o mecanismo de morte do parasito. A atividade antipromastigota e a citotoxicidade em macrófagos peritoneais foram determinadas pelo método colorimétrico do MTT após 72 horas de tratamento. O efeito antiamastigota foi avaliado em macrófagos infectados com L. amazonensis após 72 horas de incubação, corados com Giemsa e contados em microscopia óptica. Os testes para análises do mecanismo de ação foram feitos por meio de diferentes indicadores bioquímicos e celulares de parâmetros de morte celular, por fluorimetria e citometria de fluxo. Adicionalmente, foram analisados a ultraestrutura e a morfologia das promastigotas tratadas com TZDS, em microscopia eletrônica. Os resultados encontrados ressaltaram a importância dos sais de triazóis, pois a forma neutra não mostrou inibição do crescimento do parasita. Porém, o sal derivado de triazol demonstrou índice seletivo promissor (SI = 34,28) e atividade antileishmania (IC50= 0,13 μM e IC50= 2,06 μM contra formas promastigotas e amastigotas, respectivamente), provando ser mais ativo do que a miltefosina, o medicamento padrão. Em relação ao modo de ação TZDS, este composto induziu alterações mitocondriais significativas no parasita, caracterizadas por um aumento no potencial de membrana mitocondrial (ΔΨm), níveis elevados de Espécies Reativas de Oxigênio (ROS) totais e mitocondriais e acúmulo de corpos lipídicos no citoplasma. O tratamento com sal derivado de triazol também produziu várias alterações ultraestruturais, bioquímicas e celulares nas formas promastigotas, compatíveis com morte celular por apoptose-like, incluindo encolhimento celular e redução no comprimento, bem como exposição de fosfatidilserina no folheto externo da membrana plasmática e interrupção acentuada do ciclo celular, além de fragmentação de DNA. Apesar do MDC (monodansilcadaverina) positivo e da presença de vacúolos ligados à membrana que se assemelham a estruturas autofagossômicas observadas pela análise TEM, a autofagia não é um processo predominante, com danos mitocondriais graves emergindo como o evento primário que leva à morte do parasito. Esses achados demonstram o potencial antileishmania promissor do sal derivado de triazol, com seu efeito em múltiplos alvos em células de L amazonensis. Além disso, a associação do composto ativo com miltefosina mostrou um efeito aditivo no tratamento de macrófagos infectados por L. amazonensis. No geral, esses resultados destacam o potencial terapêutico do sal avaliado e dão suporte a estudos adicionais para avaliar sua eficácia in vivo em um modelo murino de leishmaniose cutânea

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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