Genes de patogenicidade de Helicobacter pylori, polimorfismos de citocinas e fatores ambientais afetam o desenvolvimento de doenças gástricas: uma visão geral

Backgrounds and objectives: Helicobacter pylori is a Gram-negative bacterium that colonizes the stomach of approximately 50% of the world´s human population. This microorganismis the major causal agent of gastritis and is an important risk factor for the development of peptic ulcer disease and gastric carcinoma. The factors that determine these diverse clinical outcomes are subject to continuous investigations and is thought to be determined by interaction of bacterial factors, host immune system and environmental variables.The aim of this review is to provide an overview of these factors that influence susceptibility to severe outcomes of H. pylori infection. Methods: For this, original and review articles were selected by searching the PubMed, CAPES Portal Journals and SCIELO bibliographic databases. Results: H. pylori possesses a set of pathogenicity factors, such as cagA, vacA, iceA, babA for colonizing the gastric mucosa and establishing a chronic infection. These bacterial factors are essential players in modulating the immune responseinvolved in the initiation of the carcinogenesis in the stomach. Host genetic factors contribute to the regulation of the inflammatory response and in the aggravation of mucosal damage once the gastric infection with H. pylori induces the mucosal production of various pro- and anti-inflammatory cytokines in the host. The harmful role of environmental factors is related to poor socioeconomic conditions, salt intake, smoking and alcohol consumption. Conclusion: By deciphering the deterministic rules – if any – of this interplay between factors of the bacterium, host and environmental variables, we will eventually be able to predict, treat, and ultimately prevent serious gastroduodenal diseases.Justificativa e objetivos: Helicobacter pylori é uma bactéria Gram negativa que coloniza o estômago de aproximadamente 50% da população humana mundial. Este microrganismo é o principal agente causal de gastrite e um importante fator de risco para o desenvolvimento de úlcera péptica e carcinoma gástrico. Os fatores que determinam essa diversidade de manifestações clínicas permanecem incertos, mas podem estar relacionados com a interação dos fatores bacterianos, sistema imune do hospedeiro e variáveis ambientais. O objetivo desta revisão é fornecer uma visão geral destes fatores que influenciam na susceptibilidade a desordens severas de infecção por H. pylori. Método: Para isso, foram selecionados artigos originais e de revisão através da pesquisa nas bases de dados bibliográficos PubMed, Portal de Periódicos CAPES e SCIELO. Resultados: H. pylori possui um conjunto de fatores de patogenicidade, tais como cagA, vacA, iceA, babA, para colonizar a mucosa gástrica e estabelecer infecção crônica. Estes fatores bacterianos são agentes essenciais em modular a resposta imune envolvida na iniciação da carcinogênesegástrica. Os fatores genéticos do hospedeiro contribuem para regular a resposta inflamatória e parao agravamento da lesão damucosa gástrica uma vez que a infecção gástrica por H. pylori induz a produção de várias citocinas pró e anti-inflamatórias no hospedeiro. O papel prejudicial dos fatores ambientais está relacionado com as precárias condições socioeconômicas, com o consumo de sal, com o tabagismo e com o consumo de álcool. Conclusão: Ao decifrar as regras deterministas - se houver - dessa interação entre fatores da bactéria, do hospedeiro e variáveis ambientais, será possível prever, tratar e, finalmente, prevenir graves doenças gastroduodenais

The interplay between mutations in cagA, 23S rRNA, gyrA and drug resistance in Helicobacter pylori

In this study, we evaluated the mutations of Helicobacter pylori associated with resistance to clarithromycin and levofloxacin. Furthermore, based on the proposed interaction between antimicrobial resistance and pathogenicity, we correlated the mutation profiles of the strains with the presence of the pathogenicity gene cagA. We analyzed 80 gastric biopsy specimens from H. pylori-infected patients for point mutations in the 23S rRNA gene region and in the gyrA gene, which are related to clarithromycin and levofloxacin resistance, respectively, and investigated the presence of the cagA gene in these strains. We observed that in the assayed biopsies, 8.7% (7/80) had mutations in the 23S rRNA gene region at positions 2143 and 2142, while 22.5% (18/80) had mutations in gyrA at codons 87 and 91. Moreover, absence of the CagA-EPIYA pathogenicity factor was observed in 68% (17/25) of resistant samples. The knowledge of the local profile of antimicrobial resistance and the complex interplay involving resistance and pathogenicity can contribute to an appropriate clinical approach

Comparative evaluation of five hydrological models in a large-scale and tropical river basin

Hydrological modeling is an important tool for water resources management, providing a feasible solution to represent the main hydrological processes and predict future streamflow regimes. The literature presents a set of hydrological models commonly used to represent the rainfallrunoff process in watersheds with different meteorological and geomorphological characteristics. The response of such models could differ significantly for a single precipitation event, given the uncertainties associated with the input data, parameters, and model structure. In this way, a correct hydrological representation of a watershed should include the evaluation of different hydrological models. This study explores the use and performance of five hydrological models to represent daily streamflow regimes at six hydropower plants located in the Tocantins river basin (Brazil). The adopted models include the GR4J, HYMOD, HBV, SMAP, and MGB-IPH. The evaluation of each model was elaborated considering the calibration (2014–2019) and validation period (2005–2010) using observed data of precipitation and climatological variables. Deterministic metrics and statistical tests were used to measure the performance of each model. For the calibration stage, results show that all models achieved a satisfactory performance with NSE values greater than 0.6. For the validation stage, only the MGB-IPH model present a good performance with NSE values greater than 0.7. A bias correction procedure were applied to correct the simulated data of conceptual models. However, the statistical tests exposed that only the MGB-IPH model could preserve the main statistical properties of the observed data. Thus, this study discusses and presents some limitations of the lumped model to represent daily streamflows in large-scale river basins (>50,000 km²)

Testing software product lines

Two studies of testing practices for software product lines identify gaps between required techniques and existing approaches in the available literature. This Web extra offers extra details for the main article (specifically, the bibliography for the two studies described)

A Deep Dive on the Impact of COVID-19 in Software Development

Context: COVID-19 pandemic has impacted different business sectors around the world. Objective. This study investigates the impact of COVID-19 on software projects and software development professionals. Method: We conducted a mining software repository study based on 100 GitHub projects developed in Java using ten different metrics. Next, we surveyed 279 software development professionals for better understanding the impact of COVID-19 on daily activities and wellbeing. Results: We identified 12 observations related to productivity, code quality, and wellbeing. Conclusions: Our findings highlight that the impact of COVID-19 is not binary (reduce productivity vs. increase productivity) but rather a spectrum. For many of our observations, substantial proportions of respondents have differing opinions from each other. We believe that more research is needed to uncover specific conditions that cause certain outcomes to be more prevalent

Salvage treatment for refractory or relapsed acute myeloid leukemia: a 10-year single-center experience

OBJECTIVES: The outcomes of refractory and relapsed acute myeloid leukemia (AML) patients in developing countries are underreported, even though the similar classic regimens are widely used. METHODS: We conducted a retrospective comparison of ‘‘MEC’’ (mitoxantrone, etoposide, and cytarabine) and ‘‘FLAG-IDA’’ (fludarabine, cytarabine, idarubicin, and filgrastim) in adults with first relapse or refractory AML. RESULTS: In total, 60 patients were included, of which 28 patients received MEC and 32 received FLAG-IDA. A complete response (CR) rate of 48.3% was observed. Of the included patients, 16 (27%) died before undergoing bone marrow assessment. No statiscally significant difference in CR rate was found between the two protocols (p=0.447). The median survival in the total cohort was 4 months, with a 3-year overall survival (OS) rate of 9.7%. In a multivariable model including age, fms-like tyrosine kinase 3 (FLT3) status, and stem-cell transplantation (SCT), only the last two indicators remained significant: FLT3-ITD mutation (hazard ratio [HR] =4.6, po0.001) and SCT (HR=0.43, p=0.01). CONCLUSION: In our analysis, there were no significant differences between the chosen regimens. High rates of early toxicity were found, emphasizing the role of supportive care and judicious selection of patients who are eligible for intensive salvage therapy in this setting. The FLT3-ITD mutation and SCT remained significant factors for survival in our study, in line with the results of previous studies

Surgical treatment of osteochondral lesions of the knee with mosaicplasty

OBJECTIVE: To evaluate the functional results of mosaicplasty in knees of patients with osteochondral lesion. METHODS: Between August 1999 and March 2005, twenty-seven patients were submitted to mosaicplasty on the knee. Twenty-one were male and six female. The patients' ages ranged from 16 to 64 years (average 38.1 years). Seventeen lesions were located on the right knee and ten on the left one. The lesion was located on the lateral condyle in 4 patients (15%), on the medial condyle in 18 patients (66.5%) and on the patella in 5 patients (18.5%). The lesion sizes varied from 1 to 8 cm² (average 2.7 cm²). The patients operated on were evaluated before and after surgery by the functional Lysholm scale, with an average follow-up of 2.5 years. RESULTS: In the preoperative evaluation, the average was 62.7 points, evolving to 95.4 points in the postoperative evaluation. The patients submitted to mosaicplasty in the lateral condyle presented an average of 51.5 points before surgery, evolving to 100 points after surgery. The patients submitted to mosaicplasty in the medial condyle had presented average of 64.1 points before surgery, evolving to 95.4 points after surgery. The patients submitted to mosaicplasty on the patella presented average of 66.4 points before surgery, evolving to 92 points in the postoperative evaluation. CONCLUSION: Mosaicplasty proved to be a good alternative for the treatment of chondral and osteochondral lesions of the knee, showing better evolution in lesions located on the femoral condyles than in lesions located on the patella.OBJETIVO: Avaliação dos resultados funcionais da técnica de mosaicoplastia em joelhos de pacientes com lesão osteocondral. MÉTODOS: No período de agosto de 1999 a março de 2005, 27 pacientes foram submetidos à mosaicoplastia do joelho. Vinte e um eram do sexo masculino e seis, do feminino. A idade variou de 16 a 64 anos (média de 38,1 anos). Dezessete lesões eram do lado direito e 10, do esquerdo. Em relação à localização da lesão, quatro (15%) situaram-se no côndilo femoral lateral, 18 (66,5%) no côndilo femoral medial e 5 (18,5%) na patela. O tamanho das lesões variou de 1 a 8cm² (média de 2,7cm²). Os pacientes operados foram avaliados no pré e pós-operatórios pela escala funcional de Lysholm, com seguimento médio de 2,5 anos. RESULTADOS: O pré-operatório teve uma média de 62,7 pontos e o pós-operatório uma média de 95,4 pontos. Os pacientes submetidos à mosaicoplastia no côndilo femoral lateral apresentaram, no pré-operatório, a média de pontos de 51,5 pontos e, no pós-operatório, média de 100 pontos. No côndilo femoral medial a média no pré-operatório foi de 64,1 pontos e, no pós-operatório, de 95,4 pontos. Com relação à patela, a média do pré-operatório foi de 66,4 pontos e, do pós-operatório, de 92 pontos. CONCLUSÃO: A mosaicoplastia mostrou-se uma boa alternativa no tratamento das lesões osteocondrais do joelho. Entretanto, apresentou melhor evolução nas lesões dos côndilos femorais em relação às localizadas na patela.UNIFESPUNIFESPUNIFESPSciEL

Avaliação de Ibicella lutea como agente antimicrobiano frente à Staphylococcus aureus

Justificative and Objectives: the study aimed the assessment of the antibacterial activity of crude extracts and fractions of Ibicella lutea, front Staphylococcus aureus, thecombination of these compounds and cytotoxic activity. Methods: was used for antibacterial activity the Microdilution Test Broth, and performed the Checkerboard Test. The extracts showed antibacterial activity were submitted to the citotoxicity test, with macrophages cell and determination of the Selectivity Index (SI). Results: The acetate etila fraction (AcOE) was better antimicrobial activity (6.25 µg/mL) compared with the others extracts and fractions used, however none of the compounds showed bactericidal activity in concentrations employed. In present study, we can be observed an additive activity between AcOE and methanolic (MeOH) fractions, and indifferent interaction between crude extracts. According to citotoxicity test, the extract which led to a higher survival rate of macrophage cells was the fraction AcOE (IC50%=30.35 µg/mL). However, when the calculated SI no satisfactory results (SI < 10) to any of the extracts was observed. Conclusions: in the present study we can observe an antimicrobial activity of the fractions AcOE and MeOH to S. aureus, as well as an additive this potential when the fractions are combined, providing support from isolation and characterization of yours active components. Despite the extracts did not showed a satisfactory SI, new toxicity studies should be performed to establish the potential use of safety with the products derived from I. lutea, such as drugs for topical and biocide products.Justificativa e Objetivos: O estudo objetivou a avaliação da atividade antibacteriana de extratos brutos e frações de Ibicella lutea, na inibição do crescimento de Staphylococcus aureus, avaliando a combinação destes compostos e sua atividade citotóxica. Métodos: Para a atividade antibacteriana dos extratos foi utilizado o Teste de Microdiluição em Caldo, seguido do Teste Checkerboard. Os extratos que apresentaram atividade antibacteriana foram submetidos ao teste de citotoxicidade, com células macrofágicas e determinação do seu Índice de Seletividade (IS). Resultados: A fração de acetato de etila(AcOE) obteve o melhor potencial antibacteriano (6,25 µg/mL), entretanto nenhum dos compostos testados apresentaram atividade bactericida nas concentrações empregadas. Neste estudo pode-se observar uma ação aditiva entre as frações AcOE e metanólica (MeOH), sendo a interação entre os extratos brutos indiferente. De acordo com o teste de citotoxicidade, a fração AcOE apresentou uma maior índice de sobrevivência das células macrofágicas (IC50%=30,35 µg/mL). Entretanto, quando calculado o IS, não houve resultados satisfatórios (IS < 10) para os extratos analisados. Conclusões: Neste estudo observou-se o potencial antibacteriano das frações AcOE e MeOH, assim como uma ação aditiva na combinação das frações, dando suporte para o isolamento e caracterização de seus componentes ativos. Apesar dos extratos não apresentarem um IS satisfatório, novos estudos de toxicidade devem ser realizados para determinar com segurança o potencial de uso dos produtos provenientes de I. lutea, como é o caso de medicamentos para uso tópico ou biocidas