LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells

Background: Although promising for graft-versus-host disease (GvHD) treatment, MSC therapy still faces important challenges. For instance, increasing MSC migratory capacity as well as potentializing immune response suppression are of interest. For GvHD management, preventing opportunistic infections is also a valuable strategy, since immunocompromised patients are easy targets for infections. LL-37 is a host defense peptide (HDP) that has been deeply investigated due to its immunomodulatory function. In this scenario, the combination of MSC and LL-37 may result in a robust combination to be clinically used. Methods: In the present study, the effects of LL-37 upon the proliferation and migratory capacity of human placenta-derived MSCs (pMSCs) were assessed by MTT and wound scratch assays. The influence of LL-37 over the immunosuppressive function of pMSCs was then investigated using CFSE cell division kit. Flow cytometry and real-time PCR were used to investigate the molecular mechanisms involved in the effects observed. Results: LL-37 had no detrimental effects over MSC proliferation and viability, as assessed by MTT assay. Moreover, the peptide promoted increased migratory behavior of pMSCs and enhanced their immunomodulatory function over activated human PBMCs. Strikingly, our data shows that LL-37 treatment leads to increased TLR3 levels, as shown by flow cytometry, and to an increased expression of factors classically related to immunosuppression, namely IDO, IL-10, TGF-β, IL-6, and IL-1β. Conclusions: Taken together, our observations may serve as groundwork for the development of new therapeutic strategies based on the combined use of LL-37 and MSCs, which may provide patients not only with an enhanced immunosuppression regime, but also with an agent to prevent opportunistic infections

The influence of genetic stability on Aspergillus fumigatus virulence and azole resistance

Genetic stability is extremely important for the survival of every living organism, and a very complex set of genes has evolved to cope with DNA repair upon DNA damage. Here, we investigated the Aspergillus fumigatus AtmA (Ataxia-telangiectasia mutated, ATM) and AtrA kinases, and how they impact virulence and the evolution of azole resistance. We demonstrated that A. fumigatus atmA and atrA null mutants are haploid and have a discrete chromosomal polymorphism. The ?atmA and ?atrA strains are sensitive to several DNA-damaging agents, but surprisingly both strains were more resistant than the wild-type strain to paraquat, menadione, and hydrogen peroxide. The atmA and atrA genes showed synthetic lethality emphasizing the cooperation between both enzymes and their consequent redundancy. The lack of atmA and atrA does not cause any significant virulence reduction in A. fumigatus in a neutropenic murine model of invasive pulmonary aspergillosis and in the invertebrate alternative model Galleria mellonela. Wild-type, ?atmA, and ?atrA populations that were previously transferred 10 times in minimal medium (MM) in the absence of voriconazole have not shown any significant changes in drug resistance acquisition. In contrast, ?atmA and ?atrA populations that similarly evolved in the presence of a subinhibitory concentration of voriconazole showed an ~5-10-fold increase when compared to the original minimal inhibitory concentration (MIC) values. There are discrete alterations in the voriconazole target Cyp51A/Erg11A or cyp51/erg11 and/or Cdr1B efflux transporter overexpression that do not seem to be the main mechanisms to explain voriconazole resistance in these evolved populations. Taken together, these results suggest that genetic instability caused by ?atmA and ?atrA mutations can confer an adaptive advantage, mainly in the intensity of voriconazole resistance acquisition.We thank the Fundação de Amparo a Pesquisa do Estado de São Paulo and the Conselho Nacional de Desenvolvimento Cientí fi co e Tecnológico, Brazil, for fi nancial support. F.R. and B.H.F. were supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (NORTE-01-0145-FEDER-000013)info:eu-repo/semantics/publishedVersio

Caderno de pós-graduação em direito: processo decisório no poder legislativo

Os trabalhos científicos ora apresentados são fruto da disciplina Processo Decisório no Poder Legislativo, ministrada no quarto bimestre de 2021 pelo Professor Doutor Ricardo José Pereira Rodrigues. No bimestre, foram trabalhados casos difíceis (hard cases), sob o prisma do Processo Decisório no âmbito do Poder Legislativo em seus desdobramentos atuais. Foram selecionados 6 (seis) artigos sobre os assuntos e textos trabalhados durante o bimestre. Os textos são de autoria dos discentes da disciplina, sendo estes e estas: João Vitor Pinto Silva Mota, Mariana da Costa Paixão, Pamela de Oliveira Leal da Silva, Rafael Ferreira Larcher, Renata Ilha Léda e Samuel da Silva Antunes

APLICABILIDADE DAS PRÁTICAS INTEGRATIVAS NO SISTEMA ÚNICO DE SAÚDE.

Objective: To discuss the applicability of integrative practices in the single health system through the existing literature. Methods: This is a qualitative integrative literature review. The search for works involved in the research was carried out in the following databases: SCIELO, LILACS, BDENF and MEDLINE, using the descriptors in health sciences: "Comprehensive health care", "Complementary therapies" and "Single health system". The inclusion criteria were: articles published between 2013 and 2023, with free access to full texts, articles in Portuguese, English and Spanish and related to the theme. Exclusion criteria were: duplicate articles, incomplete articles, abstracts, reviews, debates, articles published in event proceedings and unavailable in full. Results: The therapeutic resources that make up ICPs are diverse, and in public health services they are more frequent because they favor lower costs. Conclusion: It can be concluded that integrative practices integrated into PHC have a very satisfactory effect on users' quality of life, and should minimize medication that is often unnecessary.Objetivo: Discutir por meio da literatura existente acerca da aplicabilidade das práticas integrativas no sistema único de saúde. Métodos: Trata-se de uma revisão integrativa da literatura de caráter qualitativo. A busca dos trabalhos envolvidos na pesquisa foi realizada nas seguintes bases de dados: SCIELO, LILACS, BDENF e MEDLINE, a partir dos descritores em ciências da saúde: “Assistência integral à saúde”, “Terapias complementares” e “Sistema único de saúde”. Os critérios de inclusão foram: publicados no período entre 2013 e 2023, cujo acesso ao periódico era livre aos textos completos, artigos em idioma português, inglês e espanhol e relacionados a temática. Critérios de exclusão foram: artigos duplicados, incompletos, resumos, resenhas, debates, artigos publicados em anais de eventos e indisponíveis na íntegra. Resultados: Os recursos terapêuticos que compõe as PICs são diversas, sendo que nos serviços públicos de saúde eles são mais frequentes por favorecerem a diminuição de custos. Conclusão: Conclui-se que as práticas integrativas integradas na APS têm um efeito muito satisfatório no que diz respeito a qualidade de vida dos usuários, devendo minimizar ações medicamentosas que muitas das vezes não são necessárias

Projeto PortVix: a fala de Vitória/ES em cena

Os objetivos centrais do presente artigo são (1) apresentar à comunidade científica o projeto PortVix, que trata da fala da cidade de Vitória, capital do Espírito Santo; (2) sintetizar os trabalhos desenvolvidos e em desenvolvimento, com base nos dados deste projeto; e (3) tecer considerações sobre o alinhamento da fala de Vitória ao cenário nacional e sobre traços que a caracterizam. A Teoria da Variação e de Mudança Linguística norteia a organização da amostra e, de forma geral, a análise de diversos fenômenos variáveis, a saber, alternância entre futuro do pretérito e pretérito imperfeito; a expressão variável do futuro do presente; usos do gerúndio; variação sintática das orações adverbiais finais; alternância nós/a gente; a expressão do objeto direto anafórico; concordância nominal; concordância verbal; expressão gramatical do imperativo; alternância indicativo/subjuntivo; alternância você/cê/ocê; ausência/presença de artigo diante de antropônimos e de possessivos. Observações do senso comum e resultados das análises permitem evidenciar que, ao lado de aspectos que alinham a fala de Vitória-ES ao cenário nacional, corroborando a generalidade de diversos fenômenos, há outros aspectos que permitem inferir a caracterização da fala capixaba face aos três estados com os quais o Espírito Santo estabelece fronteiras: Rio de Janeiro, Bahia e, especialmente, Minas Gerais

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives