Gastric cancer is among the major causes of death from neoplasia leading causes of death worldwide, with high incidence rates and problems related to its treatment. Here, we outline how Geissospermum sericeum exerts antitumor activity on the ACP02 cell line (human gastric adenocarcinoma) and the mechanism of cell death. The ethanol extract and fractions, neutral fraction and alkaloid fraction, were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid (geissoschizoline N4-methylchlorine) identified by NMR. The cytotoxicity activity of the samples (ethanol extract, neutral fraction, alkaloid fraction, and geissoschizoline N4-methylchlorine) in HepG2 and VERO cells was determined by MTT. The ACP02 cell line was used to assess the anticancer potential. Cell death was quantified with the fluorescent dyes Hoechst 33342, propidium iodide, and fluorescein diacetate. The geissoschizoline N4-methylchlorine was evaluated in silico against caspase 3 and 8. In the antitumor evaluation, there was observed a more significant inhibitory effect of the alkaloid fraction (IC50 18.29 µg/mL) and the geissoschizoline N4-methylchlorine (IC50 12.06 µg/mL). However, geissoschizoline N4-methylchlorine showed lower cytotoxicity in the VERO (CC50 476.0 µg/mL) and HepG2 (CC50 503.5 µg/mL) cell lines, with high selectivity against ACP02 cells (SI 39.47 and 41.75, respectively). The alkaloid fraction showed more significant apoptosis and necrosis in 24 h and 48 h, with increased necrosis in higher concentrations and increased exposure time. For the alkaloid, apoptosis and necrosis were concentration- and time-dependent, with a lower necrosis rate. Molecular modeling studies demonstrated that geissoschizoline N4-methylchlorine could occupy the active site of caspases 3 and 8 energetically favorably. The results showed that fractionation contributed to the activity with pronounced selectivity for ACP02 cells, and geissoschizoline N4-methylchlor is a promising candidate for caspase inhibitors of apoptosis in gastric cancer. Thus, this study provides a scientific basis for the biological functions of Geissospermum sericeum, as well as demonstrates the potential of the geissoschizoline N4-methylchlorine in the treatment of gastric cancer.

O presente estudo objetivou caracterizar o perfil clinico-epidemiológico de pessoas vivendo com HIV (PVHIV) residentes no estado do Pará. Foram incluídos todos os indivíduos, independente de idade ou sexo, cujas amostras, de 2013 a 2015, foram encaminhadas ao Laboratório Central do Pará (LACEN-PA) para a realização do teste de genotipagem do HIV. Os dados foram obtidos por meio da coleta de informações nos laudos do teste de genotipagem guardados no LACEN. Foram coletadas informações como sexo, idade, nível de escolaridade, raça, ano de diagnóstico, motivos relacionados a mudança de esquema terapêutico e presença de mutações. O gênero masculino foi predominante, com faixa etária entre 40 e 50 anos ou mais, pardos e com ensino fundamental. A maioria teve o diagnóstico para o HIV entre os anos 2000 e 2009, tendo a maior parte apresentado mudanças de esquema terapêutico. Tal fato se deu em grande parte pela presença de falha terapêutica e intolerância, corroborando assim com a presença de mutações. No presente estudo observamos um perfil epidemiológico de PVHIV condizente com a literatura, caracterizado pela prevalência do gênero masculino, com faixa etária entre 40 e 50 anos ou mais, pardo e escolaridade em nível fundamental. Foi possível observar também um alto índice de mudanças nos regimes terapêuticos, de falha terapêutica, além de elevadas taxas de mutações. Demonstrando assim, a importância do exame de genotipagem não só para a escolha da terapia mais adequada como também para a adoção de estratégias que busquem melhorar a adesão de PVHIV ao tratamento com antirretrovirais. Novos estudos que possam contribuir com a compreensão e identificação das mudanças dos regimes terapêuticos assim como a contribuição destes para o aparecimento de mutações e consequente falha terapêutica são necessários.

Cross-Cultural Conflict Management ComparativeAnalysis of Eastern and Western Approaches

This study aimed to evaluate the anti-leishmania activity of extracts and fractions from stem and leaf of Montrichardia linifera against Leishmania amazonensis. The stem (EES) and leaf (EEL) extracts were obtained by maceration of powders with 96º GL alcohol. The extracts were subjected to exhaustive extraction using a reflux system and solvents of increasing polarity, obtaining 4 fractions for each extract: hexane, dichloromethane, ethyl acetate and methanol. The extracts and fractions were submitted to a phytochemical prospecting study. The antipromastigote activity and cytotoxicity in macrophages (J774) were performed using the cell viability test (MTT). In the extract and fractions of the stem, alkaloids, steroids, terpenes, flavonic heterosides, tannins, polyphenols and saponins were detected. In the extract and fractions of the leaves, coumarins, steroids, terpenes, flavonic heterosides, tannins, polyphenols and saponins were detected. In the anti-leishmania evaluation, the hexane fraction of the leaf (HFL) showed promising activity (IC50=38.56 µg/mL), and the hexane fraction of the stem (HFS) showed moderate activity (CI50=179.3 µg/mL), the extracts and the other fractions were inactive (IC50>200 µg/mL). In the cytotoxicity test, EES and HFS were cytotoxic (CC50 54.82 µg/mL and 26.95 µg/mL, respectively). EEF and HFL showed moderate cytotoxicity (CC50 of 162.7 µg/mL and 347.1 µg/mL). As for the selectivity index, the HFL showed high selectivity (SI=90). In summary, fractionation contributed to increase anti-leishmania activity and the selectivity of HFS, such activity may be related to steroids or terpenes.

Issue The National Health Plan (PNS) 2012-2016 (extended until 2020) is the Portuguese strategic health document that presents the direction of intervention within the Health System. A final evaluation of PNS was foreseen, with National Institute of Health Dr Ricardo Jorge (INSA) being responsible for carrying out this task. The experience gained by INSA in defining a roadmap to be used in this process can be important in steering other actors to policy evaluation. Description of the problem In order to analyze the impact of policies, it is necessary to collect evidence that can evaluate the results achieved, and more importantly, identify gaps in implementation and evaluation issues. Herein, we aim to present the methodological approach developed to pave the way to the final assessment of PNS. Results As part of the Biennial Collaborative Agreement 2016-2017, WHO sponsored a high-level technical consultative process with relevant experts to address the condition for defining the work plan. It was devised to undertake: i) A scoping review based upon data collected from PNS implementation evidence mapping; ii) A qualitative analysis of the perception from main stakeholders on PNS impact and their expectations. Thus, a matrix of evidence was built to analyze the alignment of PNS at national and local levels, and with the main health framework targets and indicators. Also, online surveys and face-to-face interviews were done with key stakeholders in order to identify evidence gaps and critical factors for the successful PNS implementation, among others. Lessons To characterize its implementation and impact on citizens' health, a sound PNS evaluation should be guided by clear assessment questions, supported by validated tools and complemented by international guidance. In addition, a long-term consultative process with key stakeholder support is required to properly identify opportunities, priorities, and outcomes. Key messages Institutionalization of an evaluation process as part of public policies life cycle is a powerfull tool to foster learning and crucial to achievement of proposed goals. A clear structure to support the policy evaluation approach is mandatory to guarantee impartiality, independence and transparency on the overall process.

To describe the presence of mutations and the ART resistance profile in PLHIV in Belém, Pará. Methods: This is a cross-sectional, descriptive and retrospective study, where 189 genotyping reports of individuals were included, regardless of age or sex and who were seen in the period from 2013 to 2015. Results: Most individuals had a high viral load (93%), low TCD4+ lymphocyte levels (97%) and the most prevalent HIV subtype was B (78%). We observed in this study a high presence of mutations in all classes of drugs used in ART with emphasis on M184V (ITRNN), K103N (ITRNN) and L63A/P/T/Q (PI), demonstrating that many mutations can contribute to the profile of viral resistance. Conclusion: The results presented show the importance of genotyping testing not only for choosing therapeutic and surveillance regimens, but also to contribute to patient adherence to antiretroviral treatment.

Objetivo: Caracterizar o perfil de miRNAs virais, seus mecanismos de patogênese e descrever sua interação com o hospedeiro. Métodos: Essa pesquisa é uma revisão integrativa, as palavras-chaves foram padronizadas de acordo com os Descritores em Ciências da Saúde (DeCS), as bases de dados consultadas foram o NCBI, LILACS, BVS e SciELO. Resultados: Os miRNAs regulam negativamente a sinalização IFNγ, RIGI, suprimindo a resposta imune inata, funcionam como imunomoduladores também sendo regulados positivamente e várias vias como PI3K/Akt e ERK/MAPK mantém a patogênese. A regulação negativa da sinalização do interferon tipo I, inibindo citotoxicidade de linfócitos natural killer atenua a resposta imunológica e leva a depleção do sistema imune por essas moléculas, membros da família Let-7 podem reprimir a via de apoptose por inibição de BCL2L2 potencializando infecções. Considerações finais: Os miRNAs são movidos por amplo espectro de interações, ocasionando desregulação de vias de sinalização em processos infecciosos, no entanto, essas moléculas podem ser biomarcadores terapêuticos de interesse, auxiliando no prognóstico e diagnóstico de pacientes com infecções virais.