Spider venom administration impairs glioblastoma growth and modulates immune response in a non-clinical model.

Molecules from animal venoms are promising candidates for the development of new drugs. Previous in vitro studies have shown that the venom of the spider Phoneutria nigriventer (PnV) is a potential source of antineoplastic components with activity in glioblastoma (GB) cell lines. In the present work, the effects of PnV on tumor development were established in vivo using a xenogeneic model. Human GB (NG97, the most responsive line in the previous study) cells were inoculated (s.c.) on the back of RAG-/- mice. PnV (100 µg/Kg) was administrated every 48 h (i.p.) for 14 days and several endpoints were evaluated: tumor growth and metabolism (by microPET/CT, using 18F-FDG), tumor weight and volume, histopathology, blood analysis, percentage and profile of macrophages, neutrophils and NK cells isolated from the spleen (by flow cytometry) and the presence of macrophages (Iba-1 positive) within/surrounding the tumor. The effect of venom was also evaluated on macrophages in vitro. Tumors from PnV-treated animals were smaller and did not uptake detectable amounts of 18F-FDG, compared to control (untreated). PnV-tumor was necrotic, lacking the histopathological characteristics typical of GB. Since in classic chemotherapies it is observed a decrease in immune response, methotrexate (MTX) was used only to compare the PnV effects on innate immune cells with a highly immunosuppressive antineoplastic drug. The venom increased monocytes, neutrophils and NK cells, and this effect was the opposite of that observed in the animals treated with MTX. PnV increased the number of macrophages in the tumor, while did not increase in the spleen, suggesting that PnV-activated macrophages were led preferentially to the tumor. Macrophages were activated in vitro by the venom, becoming more phagocytic; these results confirm that this cell is a target of PnV components. Spleen and in vitro PnV-activated macrophages were different of M1, since they did not produce pro- and anti-inflammatory cytokines. Studies in progress are selecting the venom molecules with antitumor and immunomodulatory effects and trying to better understand their mechanisms. The identification, optimization and synthesis of antineoplastic drugs from PnV molecules may lead to a new multitarget chemotherapy. Glioblastoma is associated with high morbidity and mortality; therefore, research to develop new treatments has great social relevance. Natural products and their derivatives represent over one-third of all new molecular entities approved by FDA. However, arthropod venoms are underexploited, although they are a rich source of new molecules. A recent in vitro screening of the Phoneutria nigriventer spider venom (PnV) antitumor effects by our group has shown that the venom significantly affected glioblastoma cell lines. Therefore, it would be relevant to establish the effects of PnV on tumor development in vivo, considering the complex neoplastic microenvironment. The venom was effective at impairing tumor development in murine xenogeneic model, activating the innate immune response and increasing tumor infiltrating macrophages. In addition, PnV activated macrophages in vitro for a different profile of M1. These activated PnV-macrophages have potential to fight the tumor without promoting tumorigenesis. Studies in progress are selecting the venom molecules with antitumor and immunomodulatory effects and trying to better understand their mechanisms. We aim to synthesize and carry out a formulation with these antineoplastic molecules for clinical trials. Spider venom biomolecules induced smaller and necrotic xenogeneic GB; spider venom activated the innate immune system; venom increased blood monocytes and the migration of macrophages to the tumor; activated PnV-macrophages have a profile different of M1 and have a potential to fight the tumor without promote tumorigenesis

Effect of different conditions and modes of application on bond strength of adhesives to dentine

Objetivo: Evaluar la resistencia de la unión microtensil en diferentes condiciones de dentina (grabado-E, sin grabado-N, seco-D y húmedo-W) de un adhesivo multimodo (Scotchbond Universal-SU, 3M/ESPE) y un adhesivo de grabado total (Ambar-AB, FGM) utilizando un dispositivo sónico (Smart Sonic Device-SD, FGM). Material y Métodos: En este estudio in vitro, noventa y seis molares humanos extraídos sanos se dividieron en 12 grupos (n=8) de acuerdo con diferentes condiciones de dentina y sistemas adhesivos. Se eliminó el esmalte y se pulieron las superficies centrales de la dentina. Cada sistema adhesivo se aplicó de acuerdo con las diferentes condiciones de dentina, y los bloques de resina compuesta se acumularon de forma incremental y se almacenaron durante 24h. Las muestras se seccionaron en barras y los datos de resistencia de la unión se analizaron con la prueba de Kruskal-Wallis y la prueba de U de Mann-Whitney. Resultado: No se observaron efectos de la aplicación sónica. En general, AB mostró resultados más bajos en comparación con el SU. Las condiciones E y N no afectaron estadísticamente la fuerza de unión de los grupos SU. La dentina seca presentó valores de fuerza de adhesión estadísticamente superiores en comparación con la dentina húmeda para el grupo SU/E/SD. Conclusión: La adhesión de la dentina seca con un sistema adhesivo multimodo puede ser superior a la dentina húmeda con aplicación sónica. Los modos de aplicación no tuvieron influencia en la resistencia de la unión de los adhesivos estudiados

Propostas de enfrentamento da violência obstétrica no SUS

Sabe-se que a violência obstétrica, no cenário epidemiológico Brasileiro, caracteriza-se como uma prática violenta de extrema relevância dada a sua alta incidência e ascensão no cenário contemporâneo. Diante disso, objetiva-se apresentar as principais sugestões de propostas de enfrentamento da violência obstétrica no sistema de saúde. Com a ampliação no número de casos de coerção obstétrica no quadro do SUS, houve a necessidade da modulação de alternativas para coibir tais práticas. Dessa forma, inúmeras medidas foram instituídas envolvendo setores de participação pública e privada na busca constante de proporcionar um atendimento humanizado às puerperias. A violência obstétrica tem ascendido cada vez mais no cenário atual e faz-se necessária a adoção de métodos e medidas que visem intervir nessa prática, a fim de se preservar a integridade física e psíquica da mulher nesse período tão importante e vulnerável da vida

Fatores relacionados à ocorrência de infecções sexualmente transmissíveis em idosos / Factors related to the occurrence of sexually transmitted infections in the elderly

O envelhecimento exige adaptação do indivíduo por conta de diversas alterações biológicas, psicológicas e sociais. Entre elas estão incluídas as respostas sexuais que também são alteradas, porém não eliminadas. Todavia, quando se refere a vida sexual na terceira idade, ainda é cercada de grandes tabus pela sociedade favorecendo uma vulnerabilidade as Infecções Sexualmente Transmissíveis (IST). Este estudo tem como objetivo descrever os fatores de risco para ocorrência de IST em idosos. Desenvolveu-se uma revisão integrativa de literatura, a partir das bases de dados: SciELO, LILACS e BIREME, admitindo a inclusão de artigos publicados no recorte temporal entre 2016 a 2020, publicações com abordagem referente a vida sexual do idoso e a ocorrência de IST e produções que tenham como idioma português. O estudo evindenciou que os idosos ainda são vistos como seres assexuados, fazendo com que abordagens por profissionais da saúde sobre vida sexual, sejam quase inexistentes. Assim como também, foi observado um baixo conhecimento quanto a forma de transmissão e prevenção, demonstrando uma vulnerabilidade a IST. Conclui-se que os idosos ainda enfrentam barreiras e possuem carência de informação no que diz respeito a prática e vivência sexual ativa de forma segura

Landscape dynamics and diversification of the megadiverse South American freshwater fish fauna

Landscape dynamics are widely thought to govern the tempo and mode of continental radiations, yet the effects of river network rearrangements on dispersal and lineage diversification remain poorly understood. We integrated an unprecedented occurrence dataset of 4,967 species with a newly compiled, time-calibrated phylogeny of South American freshwater fishes—the most species-rich continental vertebrate fauna on Earth—to track the evolutionary processes associated with hydrogeographic events over 100 Ma. Net lineage diversification was heterogeneous through time, across space, and among clades. Five abrupt shifts in net diversification rates occurred during the Paleogene and Miocene (between 30 and 7 Ma) in association with major landscape evolution events. Net diversification accelerated from the Miocene to the Recent (c. 20 to 0 Ma), with Western Amazonia having the highest rates of in situ diversification, which led to it being an important source of species dispersing to other regions. All regional biotic interchanges were associated with documented hydrogeographic events and the formation of biogeographic corridors, including the Early Miocene (c. 23 to 16 Ma) uplift of the Serra do Mar and Serra da Mantiqueira and the Late Miocene (c. 10 Ma) uplift of the Northern Andes and associated formation of the modern transcontinental Amazon River. The combination of high diversification rates and extensive biotic interchange associated with Western Amazonia yielded its extraordinary contemporary richness and phylogenetic endemism. Our results support the hypothesis that landscape dynamics, which shaped the history of drainage basin connections, strongly affected the assembly and diversification of basin-wide fish fauna

Evolution of Chagas’ disease in Brazil. Epidemiological perspective and challenges for the future: a critical review

Aims: This paper aimed to provide a critical review of the evolution of Chagas’ disease in Brazil, its magnitude, historical development and management, and challenges for the future. Methods: A literature search was performed using PubMed, SciELO and Google Scholar and throughout collected articles’ references. Narrative analysis was structured around five main themes identified: vector transmission, control program, and transfusion, oral and congenital transmission. Results: In Brazil, the Chagas’ disease Control Program was fully implemented in the 1980s, when it reached practically all the endemic areas, and in 1991, the Southern Cone Initiative was created, aiming to eliminate the disease transmission through eliminating the Triatoma infestans and controlling blood banks. As a result, the prevalence of chagasic donors in blood banks reduced from 4.4% in the 80s to 0.2% in 2005. In 2006, PAHO certified the interruption of transmission of Chagas’ disease through this vector in Brazil. However, there are still challenges, such as the domiciliation of new vector species, the need for medical care of the infected individuals, the prevention of alternative mechanisms of transmission, the loss of political concern regarding the disease and, the weakening of the control program. Conclusion: Despite the progress towards control, there are still many challenges ahead to maintain and expand such control and minimise the risk of re-emergence

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

Tratamento do calázio e novos ensaios clínicos para a oftalmologia: uma revisão integrativa

As lesões inflamatórias mais comuns na pálpebra são conhecidas como calázios, com uma prevalência variando entre 0,2% e 6%, e que ocorre com maior frequência durante a idade adulta, geralmente dos 30 aos 50 anos de idade. O objetivo do presente estudo de revisão é avaliar a eficácia clínica de novos estudos para o tratamento do calázio, documentados por meio de ensaios clínicos. Trata-se de uma pesquisa de revisão integrativa realizada por meio da base de dados PubMed, que levou em consideração os seguintes critérios de inclusão: ensaios clínicos; artigos publicados nos últimos cinco anos; que possuíam texto completo disponível e que abordassem acerca de novos ensaios clínicos no tratamento do calázio. Ficou constatada a eficácia que a utilização de tratamentos conservadores, incluindo colírios e pomadas contendo antibióticos ou esteroides possuem no tratamento de primeira linha do calázio, além do fato de que oftalmologistas podem usar opções de tratamento invasivo, a exemplo da terapia cirúrgica, como terapia inicial naqueles pacientes que possuem lesões de longa data, em razão da maior refratariedade de tais pacientes aos métodos utilizados no tratamento conservador. Além disso, verificou-se a eficácia que a microblefaroesfoliação possui como método adjuvante e não invasivo no tratamento do calázio, com eficácia de quase 90% dos casos de calázio em comparação com a higiene palpebral realizada isoladamente

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected nearly 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease-2019 (COVID-19) including two novel mRNA-based vaccines. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S), receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy