Cell-to-cell transfer of Leishmania amazonensis amastigotes is mediated by immunomodulatory LAMP-rich parasitophorous extrusions

The last step of Leishmania intracellular life cycle is the egress of amastigotes from the host cell and their uptake by adjacent cells. Using multidimensional live imaging of long-term-infected macrophage cultures we observed that Leishmania amazonensis amastigotes were transferred from cell to cell when the donor host macrophage delivers warning signs of imminent apoptosis. They were extruded from the macrophage within zeiotic structures (membrane blebs, an apoptotic feature) rich in phagolysosomal membrane components. the extrusions containing amastigotes were selectively internalized by vicinal macrophages and the rescued amastigotes remain viable in recipient macrophages. Host cell apoptosis induced by micro-irradiation of infected macrophage nuclei promoted amastigotes extrusion, which were rescued by non-irradiated vicinal macrophages. Using amastigotes isolated from LAMP1/LAMP2 knockout fibroblasts, we observed that the presence of these lysosomal components on amastigotes increases interleukin 10 production. Enclosed within host cell membranes, amastigotes can be transferred from cell to cell without full exposure to the extracellular milieu, what represents an important strategy developed by the parasite to evade host immune system.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Escola Paulista Medi, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Inst Trop Med, Lab Soroepidemiol & Imunobiol, São Paulo, BrazilFdn Oswaldo Cruz FIOCRUZ, INCT DT, Salvador, BrazilUniversidade Federal de São Paulo, Fac Med, Dept Prevent Med, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Medi, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Inst Trop Med, Lab Soroepidemiol & Imunobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Fac Med, Dept Prevent Med, São Paulo, BrazilFAPESP: 10/19335-4Web of Scienc

Corrosion Behavior of 316L and Alloy 182 Dissimilar Weld Joint with Post-Weld Heat Treatment

Austenitic stainless steel and nickel-base alloys welds are widely used in nuclear reactor components, plantsof energy generation, chemical, and petrochemical industries, due to their high corrosion resistance. The postweld heat treatments (PWHT) are generally applied to welding in order to relieve the welding residual stress.The aim of this work was to evaluate the influence of different PWHT on corrosion behavior of a dissimilarweld joint of two AISI 316L austenitic stainless steel plates with a nickel-base alloy as filler material in salineenvironments. The material was submitted to heat treatments for three hours at 600, 700 and 800 °C. Theweld joint was examined by optical microscopy to determine the effects of PWHT in the microstructure. Thecorrosion behavior of the samples before and after heat treatment was evaluated using cyclic potentiodynamicpolarization (CPP) in sodium chloride solutions (19% v/v) and pH 4.0 at room temperature. Metallographicanalyses showed that delta ferrite dissolute as PWHT temperature increased. CPP curves demonstrated anincrease of pitting corrosion resistance as the PWHT temperature rises, although the pit size has been increased.The heat treated weld joint at 600 °C showed a similar corrosion resistance compared to as-weldedmaterial.Keywords: weld joint, post-weld treatment, polarization, pitting corrosion

Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones

The present study aimed to characterize the effects of quinoxaline-derived chalcones, designed on the basis of the selective PI3Kγ inhibitor AS605240, in oral cancer cells. Three lead compounds, namely N9, N17 and N23, were selected from a series of 20 quinoxaline-derived chalcones, based on an initial screening using human and rat squamous cell carcinoma lineages, representing compounds with at least one methoxy radical at the A-ring. The selected chalcones, mainly N9 and N17, displayed marked antiproliferative effects, via apoptosis and autophagy induction, with an increase of sub-G1 population and Akt inhibition. The three chalcones displayed marked in vitro antitumor effects in different protocols with standard chemotherapy drugs, with acceptable toxicity on normal cells. There was no growth retrieval, after exposure to chalcone N9 alone, in a long-term assay to determine the cumulative population doubling (CPD) of human oral cancer cells. A PCR array evaluating 168 genes related to cancer and inflammation, demonstrated striking actions for N9, which altered the expression of 74 genes. Altogether, our results point out quinoxalinic chalcones, mainly N9, as potential strategies for oral cancer treatment

Reducción del tiempo de tratamiento antimicrobiano en unidades de cuidados intensivos en Fortaleza, Brasil

The authors are grateful for the contribution of the physicians, pharmacists and patients of the Walter Cantídio University Hospital who collaborated in the conduction of this study.Objective: To evaluate the application of the Antimicrobial (ATM) treatment time reduction strategy in Intensive Care Units (ICU) in an Antimicrobial Stewardship Program (ASP). Method: This is a descriptive and cross-sectional study, carried out in two ICU of a university hospital in Fortaleza, Brazil, from January/2017 to January/2019. Adult patients were included, accompanied by a pharmacist, and using ATM, in which the treatment time reduction strategy was applied. The evaluation of the strategy was made through the difference between the predicted time established at the beginning of the treatment and the effective days of use of each ATM. Results: Of the 100 patients included, 51.0 % were male and 64.0 % were elderly. The respiratory system was the most frequently affected by the infections (37.4 %) and the most prevalent classes of ATM were carbapenems (23.0 %) and glycopeptides (20.1 %). There was a decrease from 831 unnecessary days of antimicrobial therapy and from an average of 13.7 to 8.9 days of treatment. The greatest reductions in days were observed for meropenem, with 202 days reduced. The study also allowed the identification of associations between the reduction > 8 days of treatment and the variables length of stay > 22 days and patients in exclusive palliative care, and associations between hospi tal discharge and reductions of up to 7 days of therapy. Conclusions: The data obtained suggest that the presence of an ASP influences the practices of ATM use and its treatment time and emphasize the role of pharmaceutical professionals in these programs.Objetivo: Evaluar la aplicación de la estrategia reducción del tiempo de tratamiento Antimicrobiano (ATM) en Uni dades de Cuidados Intensivos (UCI) en un Programa Stewardship de Antimicrobiano (ASP). Método: Este es un estudio descriptivo y transversal, realizado en dos UCI de un hospital universitario de Fortaleza, Brasil, de enero/2017 a enero/2019. Se incluyeron pacientes adultos, acompañados por un farmacéutico y utilizan do ATM, en los que se aplicó la estrategia de reducción del tiempo de tratamiento. La evaluación de la estrategia se realizó a través de la diferencia entre el tiempo previsto establecido al inicio del tratamiento y los días efectivos de uso de cada ATM. Resultados: De los 100 pacientes incluidos, 51,0 % eran del sexo masculino y 64,0 % ancianos. El sistema respira torio fue el más frecuentemente afectado (37,4 %) y las clases de ATM más prevalentes fueron los carbapenémicos (23,0 %) y los glicopéptidos (20,1 %). Hubo una disminución de 831 días innecesarios de terapia antimicrobiana y de un promedio de 13,7 a 8,9 días de tratamiento. Las mayores reducciones en días se observaron para meropenem, con 202 días reducidos. El estudio también permitió identificar asociaciones entre la reducción > 8 días de trata miento y las variables estancia > 22 días y pacientes en cuidados paliativos exclusivos; y asociaciones entre alta hospitalaria y reducciones de hasta 7 días de terapia. Conclusiones: Los datos obtenidos sugieren que la presencia de un ASP influye en las prácticas de uso de ATM y su tiempo de tratamiento y enfatizan el papel de los profesionales farmacéuticos en estos programa

Reducción del tiempo de tratamiento antimicrobiano en unidades de cuidados intensivos en Fortaleza, Brasil

Objective: To evaluate the application of the Antimicrobial (ATM) treatment time reduction strategy in Intensive Care Units (ICU) in an Antimicrobial Stewardship Program (ASP). Method: This is a descriptive and cross-sectional study, carried out in two ICU of a university hospital in Fortaleza, Brazil, from January/2017 to January/2019. Adult patients were included, accompanied by a pharmacist, and using ATM, in which the treatment time reduction strategy was applied. The evaluation of the strategy was made through the difference between the predicted time established at the beginning of the treatment and the effective days of use of each ATM. Results: Of the 100 patients included, 51.0 % were male and 64.0 % were elderly. The respiratory system was the most frequently affected by the infections (37.4 %) and the most prevalent classes of ATM were carbapenems (23.0 %) and glycopeptides (20.1 %). There was a decrease from 831 unnecessary days of antimicrobial therapy and from an average of 13.7 to 8.9 days of treatment. The greatest reductions in days were observed for meropenem, with 202 days reduced. The study also allowed the identification of associations between the reduction > 8 days of treatment and the variables length of stay > 22 days and patients in exclusive palliative care, and associations between hospital discharge and reductions of up to 7 days of therapy. Conclusions: The data obtained suggest that the presence of an ASP influences the practices of ATM use and its treatment time and emphasize the role of pharmaceutical professionals in these programs.Objetivo: Evaluar la aplicación de la estrategia reducción del tiempo de tratamiento Antimicrobiano (ATM) en Unidades de Cuidados Intensivos (UCI) en un Programa Stewardship de Antimicrobiano (ASP). Método: Este es un estudio descriptivo y transversal, realizado en dos UCI de un hospital universitario de Fortaleza, Brasil, de enero/2017 a enero/2019. Se incluyeron pacientes adultos, acompañados por un farmacéutico y utilizando ATM, en los que se aplicó la estrategia de reducción del tiempo de tratamiento. La evaluación de la estrategia se realizó a través de la diferencia entre el tiempo previsto establecido al inicio del tratamiento y los días efectivos de uso de cada ATM. Resultados: De los 100 pacientes incluidos, 51,0 % eran del sexo masculino y 64,0 % ancianos. El sistema respiratorio fue el más frecuentemente afectado (37,4 %) y las clases de ATM más prevalentes fueron los carbapenémicos (23,0 %) y los glicopéptidos (20,1 %). Hubo una disminución de 831 días innecesarios de terapia antimicrobiana y de un promedio de 13,7 a 8,9 días de tratamiento. Las mayores reducciones en días se observaron para meropenem, con 202 días reducidos. El estudio también permitió identificar asociaciones entre la reducción > 8 días de tratamiento y las variables estancia > 22 días y pacientes en cuidados paliativos exclusivos; y asociaciones entre alta hospitalaria y reducciones de hasta 7 días de terapia. Conclusiones: Los datos obtenidos sugieren que la presencia de un ASP influye en las prácticas de uso de ATM y su tiempo de tratamiento y enfatizan el papel de los profesionales farmacéuticos en estos programas

Nutrição e câncer de mama: um artigo de revisão

O câncer de mama é a segunda neoplasia mais comum entre as mulheres, sendo mais prevalente em mulheres entre 40 e 60 anos. Essa neoplasia, que representa a principal causa de morte por câncer entre as mulheres brasileiras, pode ser diagnosticada a partir de exames de mamografia e de ultrassom, sobretudo em mulheres mais jovens. Estudos recentes mostram que o aparecimento e a progressão do câncer de mama pode ser influenciada pelos hábitos alimentares da mulher.  Determinar a influência da alimentação no aparecimento, na progressão e no tratamento do câncer de mama. Para esta revisão integrativa, foram analisados artigos, publicados em português e em inglês, entre os anos de 2017 e 2022, nas bases de dado Medline, Pubmed, e Scielo, usando os descritores “câncer de mama”, “nutrição”, “dieta” e “nutriente" O estudo realizado por CACAU et al mostrou que os níveis de vitaminas A, D e E, em pacientes que consultaram no serviço de mastologia estavam abaixo do recomendado, o que se torna preocupante visto que essas vitaminas são importantes na prevenção do câncer.  SOUZA et al, observou em seus estudos transversais, que a obesidade e o sobrepeso estavam intimamente relacionados com o aparecimento do câncer de mama, devido à hiperestimulação estrogênica. CICCO et al mostra que o aconselhamento de mulheres a respeito do consumo de EPA e DHA é fundamental para reduzir os efeitos da quimioterapia. JIA et al, em seus estudos detalhou o efeito de cada um dos macronutrientes no surgimento e no desenvolvimento do câncer, apontando para aqueles que têm seu consumo estimulado e aqueles que devem ter seu consumo evitado. LIMA et al mostra em sua revisão de literatura a importância de um acompanhamento farmacoterápico durante a quimioterapia. O câncer de mama sofre grande influência de hábitos alimentares, devendo, alguns alimentos, como carnes vermelhas e bebidas alcoólicas serem evitados. No entanto, ainda é necessária a realização de mais estudos a fim de verificar o impacto da alimentação em grupos com fatores de risco específicos

Respirometry and Ruminant Nutrition

The gaseous exchange between an organism and the environment is measured by respirometry or indirect calorimetry. Once the oxygen consumption (O2) and the production of carbon dioxide (CO2) and methane (CH4) are known, the energy losses by gas and heat can be calculated. Energy metabolism and methane production have been studied in the Calorimetry and Metabolism Laboratory of the Federal University of Minas Gerais, located in Belo Horizonte, Minas Gerais, Brazil. Animals used are mainly Zebu cattle and their crossbreeds that represent most beef and dairy cattle breed grazed on tropical pastures. System calibration and routine work are addressed in this text. The results obtained on respirometric chambers are expressed in net energy (NE), which can be net energy for maintenance (NEm), lactation (NEL), weight gain (NEg), and pregnancy (NEp). NE is, in fact, what is used by the animal for maintenance and each productive function. The values of k (conversion efficiency of ME into NE) for maintenance (km), milk (kL), weight gain or growth (kg), and pregnancy (kp) are determined. Thanks to the peculiarity of the respirometric technique, the same animal can be evaluated several times, in different physiological states and planes of nutrition

Early reduction in PD-L1 expression predicts faster treatment response in human cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) is caused by Leishmania donovani in Sri Lanka. Pentavalent antimonials (e.g. sodium stibogluconate; SSG) remain first line drugs for CL with no new effective treatments emerging. We studied whole blood and lesion transcriptomes from Sri Lankan CL patients at presentation and during SSG treatment. From lesions but not whole blood, we identified differential expression of immune-related genes, including immune checkpoint molecules, after onset of treatment. Using spatial profiling and RNA-FISH, we confirmed reduced expression of PD-L1 and IDO1 proteins on treatment in lesions of a second validation cohort and further demonstrated significantly higher expression of these checkpoint molecules on parasite-infected compared to non-infected lesional CD68+ monocytes / macrophages. Crucially, early reduction in PD-L1 but not IDO1 expression was predictive of rate of clinical cure (HR = 4.88) and occurred in parallel with reduction in parasite load. Our data support a model whereby the initial anti-leishmanial activity of antimonial drugs alleviates checkpoint inhibition on T cells, facilitating immune-drug synergism and clinical cure. Our findings demonstrate that PD-L1 expression can be used as predictor of rapidity of clinical response to SSG treatment in Sri Lanka and support further evaluation of PD-L1 as a host directed therapy target in leishmaniasis

Condutas iniciais na Síndrome Coronariana aguda e seu desfecho sobre os quadros de Taquiarritmias: uma revisão sistemática com metanálise: Initial conducts in acute Coronary Syndrome and its outcome on Tachyarrhythmia frames: a systematic review with meta-analysis

Este artigo tem por objetivo realizar uma revisão sistemática de literatura sobre condutas iniciais diante de um quadro síndrome coronariana aguda e seu impacto sobre quadros de taquiarritmias. Trata-se de uma revisão sistemática de literatura baseada em buscas nas bases de dados Biblioteca Virtual em Saúde – BVS, Google Acadêmico, Lilacs, Pubmed e Scientific Electronic Library Online – SciELO. A pesquisa utilizou-se dos seguintes descritores, segundo o DeCS, com seus correspondentes no idioma inglês e espanhol: Arritmias Cardíacas; Taquicardia; Síndrome Coronariana Aguda. Os principais resultados obtidos apontam que a síndrome coronariana aguda, um evento isquêmico do miocárdio, decorrente da hipoperfusão cardíaca, pode resultar em taquiarritmias supraventriculares (TSV) e ventriculares (TV), tendo seu desfecho clínico e prognóstico dependente do intervalo de tempo desde o início do evento e do tipo de taquiarritmia desencadeada. A partir disto, surge a questão sobre quais condutas iniciais tomadas diante de SCA minimizaria desfechos clínicos de taquiarritmias, a fim de garantir um manejo adequado e minimização da morbimortalidade