Trypanosoma cruzi killing and immune response boosting by novel phenoxyhydrazine-thiazole against Chagas disease.

Trypanosoma cruzi (T. cruzi) causes Chagas, which is a neglected tropical disease (NTD). WHO estimates that 6 to 7 million people are infected worldwide. Current treatment is done with benznidazole (BZN), which is very toxic and effective only in the acute phase of the disease. In this work, we designed, synthesized, and characterized thirteen new phenoxyhydrazine-thiazole compounds and applied molecular docking and in vitro methods to investigate cell cytotoxicity, trypanocide activity, nitric oxide (NO) production, cell death, and immunomodulation. We observed a higher predicted affinity of the compounds for the squalene synthase and 14-alpha demethylase enzymes of T. cruzi. Moreover, the compounds displayed a higher predicted affinity for human TLR2 and TLR4, were mildly toxic in vitro for most mammalian cell types tested, and LIZ531 (IC50 2.8 µM) was highly toxic for epimastigotes, LIZ311 (IC50 8.6 µM) for trypomastigotes, and LIZ331 (IC50 1.9 µM) for amastigotes. We observed that LIZ311 (IC50 2.5 µM), LIZ431 (IC50 4.1 µM) and LIZ531 (IC50 5 µM) induced 200 µg/mL of NO and JM14 induced NO production in three different concentrations tested. The compound LIZ331 induced the production of TNF and IL-6. LIZ311 induced the secretion of TNF, IFNγ, IL-2, IL-4, IL-10, and IL-17, cell death by apoptosis, decreased acidic compartment formation, and induced changes in the mitochondrial membrane potential. Taken together, LIZ311 is a promising anti-T. cruzi compound is not toxic to mammalian cells and has increased antiparasitic activity and immunomodulatory properties.

Cultural adaptation and validity evidence of the Student Nurse Stressor-15 (SNS-15) Scale for Brazil.

OBJECTIVES: to carry out the cultural adaptation and evaluation of validity evidence of the Student Nurse Stressor-15 (SNS-15) Scale for use in Brazil. METHODS: psychometric study, conducted from the stages of translation, synthesis, back-translation, review by a committee of seven experts, pre-test and evaluation of measurement properties with 32 and 238 nursing students, respectively. Descriptive statistics, Exploratory Factor Analysis (EFA), and Confirmatory Factor Analysis (CFA) were performed. The reliability of the instrument was estimated using McDonald's Omega (ω). RESULTS: EFA subsidized the distribution of the fifteen SNS-15 items into four factors. Using AFC, satisfactory fit indices were achieved (Comparative Fit Index = 0.94; Tucker-Lewis Index = 0.93; Root Mean Square Error of Approximation = 0.06; Standardized Root Mean Square Residual = 0.16) and ω = 0.86. CONCLUSIONS: the Brazilian version of the SNS-15 presents evidence that confirms its validity and reliability.

Phytochemical profile and biological activities of Bromelia antiacantha extracts

Abstract Reports from popular medicine usually act as a basis for the development of new drugs from natural compounds with therapeutic actions for serious diseases and prevalence such as cancer. Bromelia antiacantha Bertol. is a species of the Bromeliaceae family, considered an unconventional food plant, found in the south and midwest regions of Brazil. Despite the high nutritional content and pharmacological potential of its fruits, few scientific studies report its biological actions. Thus, this study evaluates the phytochemical profile of aqueous and ethanol extracts obtained from B. antiacantha fruits, as well as their possible antioxidant, antitumor, and cytotoxic activities. The aqueous extract exhibited phenolic compounds and flavonoids, while ethanol extracts indicated the presence of flavonoids and coumarin in their composition, regardless of the region of collection. The ethanolic extract demonstrated a more promising antioxidant effect than the aqueous extract and also induced a significant inhibition in the viability of human cervical cancer cells of the SiHa strain. In addition, treatment with both extracts did not alter the viability of non-tumor cells of the immortalized human keratinocyte lineage (HaCaT). These results bring new data about extracts obtained from a native plant, edible and traditionally used in popular medicine, opening new perspectives for its possible therapeutic application.

Resumo Relatos da medicina popular costumam atuar como referencial para o desenvolvimento de novos fármacos a partir de moléculas naturais com ações terapêuticas para doenças de alta gravidade e prevalência como o câncer. Bromelia antiacantha Bertol. é uma espécie da família Bromeliaceae, considerada uma planta alimentícia não convencional (PANC), encontrada nas regiões sul e centro-oeste do Brasil. Apesar do alto teor nutritivo e potencial farmacológico de seus frutos, poucos estudos científicos relatam suas ações biológicas. Desta forma, este estudo avalia o perfil fitoquímico de extratos aquoso e etanólico obtidos de frutos de B. antiacantha, bem como a sua possível ação antioxidante, antitumoral e citotóxica. O extrato aquoso apresentou compostos fenólicos e flavonoides, enquanto os extratos etanólicos apontam a presença de flavonóides e cumarina em sua composição, independente da região de coleta. O extrato etanólico demonstrou efeito antioxidante mais promissor do que o extrato aquoso e também induziu uma inibição significativa na viabilidade de células humanas de câncer cervical da linhagem SiHa. Além disso, o tratamento com ambos extratos não alterou a viabilidade de células não tumorais da linhagem de queratinócitos humanos imortalizados (HaCaT). Estes dados trazem novas informações sobre extratos obtidos de uma espécie vegetal nativa, comestível e já utilizada tradicionalmente, mas abrindo novas perspectivas quanto a possíveis aplicações terapêuticas.

Phytochemical profile and biological activities of Bromelia antiacantha extracts / Perfil fitoquímico e atividades biológicas de extratos de Bromelia antiacantha

Reports from popular medicine usually act as a basis for the development of new drugs from natural compounds with therapeutic actions for serious diseases and prevalence such as cancer. Bromelia antiacantha Bertol. is a species of the Bromeliaceae family, considered an unconventional food plant, found in the south and midwest regions of Brazil. Despite the high nutritional content and pharmacological potential of its fruits, few scientific studies report its biological actions. Thus, this study evaluates the phytochemical profile of aqueous and ethanol extracts obtained from B. antiacantha fruits, as well as their possible antioxidant, antitumor, and cytotoxic activities. The aqueous extract exhibited phenolic compounds and flavonoids, while ethanol extracts indicated the presence of flavonoids and coumarin in their composition, regardless of the region of collection. The ethanolic extract demonstrated a more promising antioxidant effect than the aqueous extract and also induced a significant inhibition in the viability of human cervical cancer cells of the SiHa strain. In addition, treatment with both extracts did not alter the viability of non-tumor cells of the immortalized human keratinocyte lineage (HaCaT). These results bring new data about extracts obtained from a native plant, edible and traditionally used in popular medicine, opening new perspectives for its possible therapeutic application.

Relatos da medicina popular costumam atuar como referencial para o desenvolvimento de novos fármacos a partir de moléculas naturais com ações terapêuticas para doenças de alta gravidade e prevalência como o câncer. Bromelia antiacantha Bertol. é uma espécie da família Bromeliaceae, considerada uma planta alimentícia não convencional (PANC), encontrada nas regiões sul e centro-oeste do Brasil. Apesar do alto teor nutritivo e potencial farmacológico de seus frutos, poucos estudos científicos relatam suas ações biológicas. Desta forma, este estudo avalia o perfil fitoquímico de extratos aquoso e etanólico obtidos de frutos de B. antiacantha, bem como a sua possível ação antioxidante, antitumoral e citotóxica. O extrato aquoso apresentou compostos fenólicos e flavonoides, enquanto os extratos etanólicos apontam a presença de flavonóides e cumarina em sua composição, independente da região de coleta. O extrato etanólico demonstrou efeito antioxidante mais promissor do que o extrato aquoso e também induziu uma inibição significativa na viabilidade de células humanas de câncer cervical da linhagem SiHa. Além disso, o tratamento com ambos extratos não alterou a viabilidade de células não tumorais da linhagem de queratinócitos humanos imortalizados (HaCaT). Estes dados trazem novas informações sobre extratos obtidos de uma espécie vegetal nativa, comestível e já utilizada tradicionalmente, mas abrindo novas perspectivas quanto a possíveis aplicações terapêuticas.

Cultural adaptation and validity evidence of the Student Nurse Stressor-15 (SNS-15) Scale for Brazil / Adaptación cultural y evidencia de validez de la Student Nurse Stressor-15 (SNS-15) Scale para Brasil / Adaptação cultural e evidências de validade da Student Nurse Stressor-15 (SNS-15) Scale para o Brasil

ABSTRACT Objectives: to carry out the cultural adaptation and evaluation of validity evidence of the Student Nurse Stressor-15 (SNS-15) Scale for use in Brazil. Methods: psychometric study, conducted from the stages of translation, synthesis, back-translation, review by a committee of seven experts, pre-test and evaluation of measurement properties with 32 and 238 nursing students, respectively. Descriptive statistics, Exploratory Factor Analysis (EFA), and Confirmatory Factor Analysis (CFA) were performed. The reliability of the instrument was estimated using McDonald's Omega (ω). Results: EFA subsidized the distribution of the fifteen SNS-15 items into four factors. Using AFC, satisfactory fit indices were achieved (Comparative Fit Index = 0.94; Tucker-Lewis Index = 0.93; Root Mean Square Error of Approximation = 0.06; Standardized Root Mean Square Residual = 0.16) and ω = 0.86. Conclusions: the Brazilian version of the SNS-15 presents evidence that confirms its validity and reliability.

RESUMEN Objetivos: realizar adaptación cultural y evaluación de evidencia de validez de la Student Nurse Stressor-15 (SNS-15) Scale para su uso en Brasil. Métodos: estudio psicométrico, realizado desde las etapas de traducción, síntesis, retrotraducción, revisión por un comité de siete expertos, pretest y evaluación de propiedades de medición con 32 y 238 estudiantes de enfermería, respectivamente. Se realizó estadística descriptiva, Análisis Factorial Exploratorio (AFE), Análisis Factorial Confirmatorio (AFC). La confiabilidad del instrumento se estimó mediante el Omega de McDonald (ω). Resultados: AFE subvencionó la distribución de los quince ítems del SNS-15 en cuatro factores. A través de la AFC se lograron índices de ajuste satisfactorios (Comparative Fit Index = 0,94; Tucker-Lewis Index = 0,93; Root Mean Square Error of Approximation = 0,06; Standardized Root Mean Square Residual = 0,16) y ω = 0,86. Conclusiones: la versión brasileña del SNS-15 presenta evidencias que confirman su validez y confiabilidad.

RESUMO Objetivos: realizar a adaptação cultural e a avaliação das evidências de validade da Student Nurse Stressor-15 (SNS-15) Scale para uso no Brasil. Métodos: estudo psicométrico, conduzido a partir das etapas de tradução, síntese, retrotradução, revisão por um comitê de sete especialistas, pré-teste e avaliação das propriedades de medida com 32 e 238 estudantes de enfermagem, respectivamente. Realizou-se estatística descritiva, Análise Fatorial Exploratória (AFE), Análise Fatorial Confirmatória (AFC). Estimou-se a confiabilidade do instrumento através do Ômega de McDonald's (ω). Resultados: a AFE subsidiou a distribuição dos quinze itens da SNS-15 em quatro fatores. Mediante AFC, alcançou-se índices satisfatórios de ajuste (Comparative Fit Index = 0,94; Tucker-Lewis Index = 0,93; Root Mean Square Error of Approximation = 0,06; Standardized Root Mean Square Residual = 0,16) e ω = 0,86. Conclusões: a versão brasileira da SNS-15 apresenta evidências que confirmam sua validade e confiabilidade.

The Effects of Different Exercise Training Types on Body Composition and Physical Performance in Older Adults with Sarcopenic Obesity: A Systematic Review and Meta-Analysis.

OBJECTIVES: To carry out a systematic review and meta-analysis to verify the effects of different exercise training types on body composition and physical performance in older adults with sarcopenic obesity (SO). DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Older adults (≥60 years). METHODS: Database searches were performed in MEDLINE (via PubMed), EMBASE, Cochrane Library, Web of Science, SCOPUS, and LILACS on January 10th, 2023. We included: randomized and/or controlled clinical trials; physical exercise as an intervention; analysis of body composition and/or muscle function; and sarcopenic obesity diagnosis. We used the Risk of Bias 2 tool and PEDro scale. The GRADE certainty of evidence was also performed. RESULTS: Fourteen studies were included in the systematic review and nine studies in the meta-analysis. A decrease in body fat (%) favoring the exercise group was identified (SMD: -0.34 [95% CI: -0.53 to -0.16]; p=0.0003) (GRADE: ⊕⊕⊕◯ Moderate). Only resistance training showed fat reduction (SMD: -0.27 [95% CI: -0.48 to -0.06]; p=0.01). Increases in upper (SMD: 0.41 [95% CI: 0.04 to 0.78]; p=0.03) (GRADE: ⊕⊕◯◯ Low) and lower (SMD: 0.80 [95% CI: 0.22 to 1.39]; p=0.007) (GRADE: ⊕⊕⊕⊕ High) limb strength was identified with exercise. Chair stand test showed increases with exercise (SMD: 0.73 [95% CI: 0.40 to 1.07]; p<0.0001) (GRADE: ⊕⊕⊕⊕ High), especially for resistance training (SMD: 0.62 [95% CI: 0.21 to 1.02]; p=0.003) and combined training (SMD: 0.99 [95% CI: 0.40 to 1.57]; p=0.0005). The PEDro scale for the studies in our review ranged from 3 to 8 (mean = 5.8 (1.6)), meaning fair methodological quality, and most studies were overall judged with at least low/some concerns in terms of risk of bias. CONCLUSION AND IMPLICATIONS: Overall, moderate to high certainty of evidence was found for body fat, lower limb strength, and chair stand test. On the other hand, low certainty of evidence was found for upper limb strength. Resistance, combined, and aerobic training evoked divergent results between the variables analyzed. Although promising, our results should be considered sparingly, but may guide additional exercise recommendations to improve specific health parameters in older adults with SO.

The Response of Paracoccidioides lutzii to the Interaction with Human Neutrophils.

The fungal pathogen Paracoccidioides lutzii causes systemic mycosis Paracoccidioidomycosis (PCM), which presents a broad distribution in Latin America. Upon infection, the fungus undergoes a morphological transition to yeast cells and provokes an inflammatory granulomatous reaction with a high number of neutrophils in the lungs. In this work, we employed proteomic analysis to investigate the in vitro response of the fungus to the interaction with human neutrophils. Proteomic profiling of P. lutzii yeast cells harvested at 2 and 4 h post interaction with human polymorphonuclear cells allowed the identification of 505 proteins differentially accumulated. The data indicated that P. lutzii yeast cells underwent a shift in metabolism from glycolysis to Beta oxidation, increasing enzymes of the glyoxylate cycle and upregulating enzymes related to the detoxification of oxidative and heat shock stress. To our knowledge, this is the first study employing proteomic analysis in the investigation of the response of a member of the Paracoccidioides genus to the interaction with neutrophils.

Proteomic Profiling of Paracoccidioides brasiliensis in Response to Phenacylideneoxindol Derivative: Unveiling Molecular Targets and Pathways.

BACKGROUND: The treatment of paracoccidioidomycosis (PCM) is a challenge, and the discovery of new antifungal compounds is crucial. The phenacylideneoxindoles exhibited promising antifungal activity against Paracoccidioides spp., but their mode of action remains unknown. METHODS: Through proteomic analysis, we investigated the effects of (E)-3-(2-oxo-2-phenylethylidene)indolin-2-one on P. brasiliensis. In addition, we investigated the metabolic alterations of P. brasiliensis in response to the compound. Furthermore, the effects of the compound on the membrane, ethanol production, and reactive oxygen species (ROS) production were verified. RESULTS: We identified differentially regulated proteins that revealed significant metabolic reorganization, including an increase in ethanol production, suggesting the activation of alcoholic fermentation and alterations in the rigidity of fungal cell membrane with an increase of the ergosterol content and formation of ROS. CONCLUSIONS: These findings enhance our understanding of the mode of action and response of P. brasiliensis to the investigated promising antifungal compound, emphasizing its potential as a candidate for the treatment of PCM.

Sirtuins: Key pieces in the host response to pathogens' puzzle.

Global warming is changing the distribution of different pathogens around the globe, and humans are more susceptible to new or re-emerging infections. The human response to microbes is complex and involves different mechanisms of the immune system. Regulation of gene expression of immunity genes and of metabolism of immune cells are essential in this process. Both mechanisms could be regulated by protein lysine acetylation that will control chromatin structure affecting gene expression or key enzyme activity involved in cellular processes. Protein acetylation is crucial for the immunity and involves two families of enzymes: lysine acetyltransferases (KATs), which will promote protein acetylation, and lysine deacetylases (KDACs) that will reduce this modification. Lysine deacetylases are divided into Zinc-dependent or HDACs and NAD+ -dependent, or Sirtuins. These enzymes are in the nucleus, cytosol, and mitochondria of mammalian cells affecting different cellular pathways, such as metabolism, gene expression, DNA repair, cell proliferation, and apoptosis, opening the opportunity to explore these proteins as drug targets in different diseases, including cancer and neurodegenerative illness. Although widely explored in chronic diseases, very little is known about the role of Sirtuins during host response against microbes' infection. In this review we aim to explore the most recent literature evidencing a role for these enzymes during host responses to viruses, bacterial and protozoan infections, pointing out how these proteins can be manipulated by these pathogens to progress in the infection. Moreover, we will uncover the potential of host KDACs as therapeutic targets to prevent infections by activating effector immune functions.

1,3-Thiazole derivatives as privileged structures for anti-Trypanosoma cruzi activity: Rational design, synthesis, in silico and in vitro studies.

Chagas disease is a deadly and centenary neglected disease that is recently surging as a potential global threat. Approximately 30% of infected individuals develop chronic Chagas cardiomyopathy and current treatment with the reference benznidazole (BZN) is ineffective for this stage. We presently report the structural planning, synthesis, characterization, molecular docking prediction, cytotoxicity, in vitro bioactivity and mechanistic studies on the anti-T. cruzi activity of a series of 16 novel 1,3-thiazoles (2-17) derived from thiosemicarbazones (1a, 1b) in a two-step and reproducible Hantzsch-based synthesis approach. The anti-T. cruzi activity was evaluated in vitro against the epimastigote, amastigote and trypomastigote forms of the parasite. In the bioactivity assays, all thiazoles were more potent than BZN against epimastigotes. We found that the compounds presented an overall increased anti-tripomastigote selectivity (Cpd 8 was 24-fold more selective) than BZN, and they mostly presented anti-amastigote activity at very low doses (from 3.65 µM, cpd 15). Mechanistic studies on cell death suggested that the series of 1,3-thiazole compounds herein reported cause parasite cell death through apoptosis, but without compromising the mitochondrial membrane potential. In silico prediction of physicochemical properties and pharmacokinetic parameters showed promising drug-like results, being all the reported compounds in compliance with Lipinski and Veber rules. In summary, our work contributes towards a more rational design of potent and selective antitripanosomal drugs, using affordable methodology to yield industrially viable drug candidates.

Positive and negative aspects of psychological stress in clinical education in nursing: A scoping review.

BACKGROUND: Even though clinical practice is crucial for nursing students' personal and professional development, it is recurrently associated with stress. However, stressful situations may not only elicit negative responses, but positive responses as well, and such aspects should be further investigated. AIM: To explore the literature addressing the positive and negative aspects of stress experienced by nursing students during clinical practicum. DESIGN: This scoping review followed the Joanna Briggs Institute (JBI) and PRISMA-ScR guidelines. DATA SOURCES: CINAHL, MEDLINE/PubMed, PsycINFO, Web of Science, IBECS, LILACS, BDENF and two theses and dissertations repositories. REVIEW METHODS: Searches were conducted from June to August 2022. Studies addressing the positive and negative aspects of stress experienced by nursing students during clinical practice were included regardless of the method adopted. RESULTS: This review included 32 studies published between 1999 and 2022 in 25 countries across four continents: Africa, America, Asia, and Europe. Stress can positively influence academic performance, especially in mobilizing a search for learning and professional development and in integrating theoretical knowledge and improving clinical skills and competencies. Negatively, stress can cause biopsychosocial symptoms that compromise a student's academic performance and can cause doubts and uncertainties about the construction of their professional identity. CONCLUSIONS: Although the negative aspects stand out over the positive ones, it is evident that both are present in the clinical practice environment. When considering stress of nursing students, educators should conduct the teaching-learning process in order to reduce the negative impact and promote the positive side of stressful situations.

Fátima Sampaio: vida e trajetória profissional como marcos da história da enfermagem / Fátima Sampaio: life and professional history as marks in the history of nursing / Fátima Sampaio: vida e historia profesional como marcas en la historia de la enfermería

Objetivo: descrever a trajetória profissional da piauiense Maria do Rozário de Fátima Borges Sampaio no ensino, na gestão e nos Conselhos Federal e Regional de Enfermagem. Métodos: estudo de natureza histórico-biográfica, embasado na metodologia da história oral de vida, cuja construção foi fundamentada em fontes orais, entrevista semiestruturada; e escritas, como atas, resoluções e comunicados disponibilizados pelo Conselho Federal de Enfermagem e Conselho Regional de Enfermagem ­ seção Piauí. A análise dos dados ocorreu para articular as informações captadas nas fontes para se construir a narrativa histórica. Resultados: Foram apresentados em dois quadros, que deram origem a três categorias discursivas: Vida e formação ­ de menina do interior à mestre; Ensino e gestão ­ todo enfermeiro é um educador e um gestor; Entidades de classe ­ representação da enfermagem e do Piauí. Conclusão: a história de Maria do Rozário de Fátima Borges Sampaio mostra uma mulher determinada e compromissada com a profissão, forte para enfrentar desafios, sensível no trato com o paciente e a complexidade deste, questionadora, estudiosa, dedicada e ética nas decisões, tanto no que se refere à assistência de enfermagem quanto às deliberações voltadas aos órgãos dos quais participou e presidiu. (AU)

Objective: to describe the professional trajectory of Maria do Rozário de Fátima Borges Sampaio, from Piauí, in teaching, management and in the Federal and Regional Councils of Nursing. Methods: a historical-biographical study, based on the methodology of oral history of life, whose construction was based on oral sources, semi-structured interviews, and written sources, such as minutes, resolutions, and communications made available by the Federal Council of Nursing and the Regional Council of Nursing - Piauí section. Data analysis occurred to articulate the information captured in the sources to build the historical narrative. Results: They were presented in two tables, which gave rise to three discursive categories: Life and training - from countryside girl to master; Teaching and management - every nurse is an educator and a manager; Class entities - representation of nursing and Piauí. Conclusion: the history of Maria do Rozário de Fátima Borges Sampaio shows a woman determined and committed to the profession, strong to face challenges, sensitive in dealing with patients and their complexity, questioning, studious, dedicated and ethical in her decisions, both in terms of nursing care and in terms of the deliberations focused on the bodies of which she participated and presided. (AU)

Objetivo: describir la trayectoria profesional de Maria do Rozário de Fátima Borges Sampaio, de Piauí, en la docencia, la gestión y en los Consejos Federal y Regional de Enfermería. Métodos: estudio de naturaleza histórico-biográfica, basado en la metodología de la historia oral de la vida, cuya construcción se fundamenta en fuentes orales, entrevistas semiestructuradas; y escritas, como atas, resoluciones y comunicados disponibles por el Consejo Federal de Enfermería y el Consejo Regional de Enfermería - sede Piauí. El análisis de los datos se produjo para articular la información captada en las fuentes para construir el relato histórico. Resultados: Se presentaron en dos cuadros, que dieron lugar a tres categorías discursivas: Vida y formación - de campesina a maestra; Enseñanza y gestión - toda enfermera es educadora y gestora; Entidades de clase - representación de la enfermería y de Piauí. Conclusión: la historia de Maria do Rozário de Fátima Borges Sampaio muestra a una mujer decidida y comprometida con la profesión, fuerte para afrontar los retos, sensible en el trato con los pacientes y su complejidad, cuestionadora, estudiosa, dedicada y ética en sus decisiones, tanto en lo que se refiere a los cuidados de enfermería como a las deliberaciones centradas en los órganos de los que participó y presidió. (AU)

Molecular Interactions of the Copper Chaperone Atx1 of Paracoccidioides brasiliensis with Fungal Proteins Suggest a Crosstalk between Iron and Copper Homeostasis.

Paracoccidioides spp. are endemic fungi from Latin America that cause Paracoccidioidomycosis, a systemic disease. These fungi present systems for high-affinity metal uptake, storage, and mobilization, which counteract host nutritional immunity and mitigate the toxic effects of metals. Regarding Cu mobilization, the metallochaperone Atx1 is regulated according to Cu bioavailability in Paracoccidioides spp., contributing to metal homeostasis. However, additional information in the literature on PbAtx1 is scarce. Therefore, in the present work, we aimed to study the PbAtx1 protein-protein interaction networks. Heterologous expressed PbAtx1 was used in a pull-down assay with Paracoccidioides brasiliensis cytoplasmic extract. Nineteen proteins that interacted with PbAtx1 were identified by HPLC-MSE. Among them, a relevant finding was a Cytochrome b5 (PbCyb5), regulated by Fe bioavailability in Aspergillus fumigatus and highly secreted by P. brasiliensis in Fe deprivation. We validated the interaction between PbAtx1-PbCyb5 through molecular modeling and far-Western analyses. It is known that there is a relationship between Fe homeostasis and Cu homeostasis in organisms. In this sense, would PbAtx1-PbCyb5 interaction be a new metal-sensor system? Would it be supported by the presence/absence of metals? We intend to answer those questions in future works to contribute to the understanding of the strategies employed by Paracoccidioides spp. to overcome host defenses.

Evaluating TROPOMI and MODIS performance to capture the dynamic of air pollution in São Paulo state: A case study during the COVID-19 outbreak.

Atmospheric pollutant data retrieved through satellite sensors are continually used to assess changes in air quality in the lower atmosphere. During the COVID-19 pandemic, several studies started to use satellite measurements to evaluate changes in air quality in many different regions worldwide. However, although satellite data is continuously validated, it is known that its accuracy may vary between monitored areas, requiring regionalized quality assessments. Thus, this study aimed to evaluate whether satellites could measure changes in the air quality of the state of São Paulo, Brazil, during the COVID-19 outbreak; and to verify the relationship between satellite-based data [Tropospheric NO2 column density and Aerosol Optical Depth (AOD)] and ground-based concentrations [NO2 and particulate material (PM; coarse: PM10 and fine: PM2.5)]. For this purpose, tropospheric NO2 obtained from the TROPOMI sensor and AOD retrieved from MODIS sensor data by using the Multi-Angle Implementation of Atmospheric Correction (MAIAC) algorithm were compared with concentrations obtained from 50 automatic ground monitoring stations. The results showed low correlations between PM and AOD. For PM10, most stations showed correlations lower than 0.2, which were not significant. The results for PM2.5 were similar, but some stations showed good correlations for specific periods (before or during the COVID-19 outbreak). Satellite-based Tropospheric NO2 proved to be a good predictor for NO2 concentrations at ground level. Considering all stations with NO2 measurements, correlations >0.6 were observed, reaching 0.8 for specific stations and periods. In general, it was observed that regions with a more industrialized profile had the best correlations, in contrast with rural areas. In addition, it was observed about 57% reductions in tropospheric NO2 throughout the state of São Paulo during the COVID-19 outbreak. Variations in air pollutants were linked to the region economic vocation, since there were reductions in industrialized areas (at least 50% of the industrialized areas showed >20% decrease in NO2) and increases in areas with farming and livestock characteristics (about 70% of those areas showed increase in NO2). Our results demonstrate that Tropospheric NO2 column densities can serve as good predictors of NO2 concentrations at ground level. For MAIAC-AOD, a weak relationship was observed, requiring the evaluation of other possible predictors to describe the relationship with PM. Thus, it is concluded that regionalized assessment of satellite data accuracy is essential for assertive estimates on a regional/local level. Good quality information retrieved at specific polluted areas does not assure a worldwide use of remote sensor data.

Chemokine receptors on human regulatory T cells during cutaneous leishmaniasis.

The aim of this work was to define the population of regulatory T cells (Tregs) which are circulating in the blood of Leishmania infected individuals clinically displaying a lesion (active disease-AD) and sub-clinical (SC) ones. We have individually collected blood samples, processed the PBMC and stained with fluorochrome-conjugated antibodies against CD3, CD4, Foxp3, CD25, CTLA-4, Ki-67, CCR4, CCR5, and CCR7. Cells were analyzed by flow cytometry. Our results suggest that CD25 and CTLA-4 are upregulated in Tregs of AD patients when compared to SC and uninfected (UN) controls. Moreover, Tregs proliferate upon infection based on Ki-67 nuclear antigen staining. Finally, we have observed that these Tregs of SC and AD patients upregulate CCR4, but not CCR5 and CCR7. There is an increase in the number of circulating Tregs in the blood of Leishmania infected individuals. These cells are potentially more suppressive based on the increased upregulation of CD25 and CTLA-4 during clinical infection (AD) when compared to SC infection. Tregs of both SC and AD cohorts are proliferating and express CCR4, which potentially guide them to the skin, but do not upregulate CCR5 and CCR7.

New Methylcitrate Synthase Inhibitor Induces Proteolysis, Lipid Degradation and Pyruvate Excretion in Paracoccidioides brasiliensis.

BACKGROUND: Paracoccidioidomycosis is a systemic mycosis caused by the inhalation of conidia of the genus Paracoccidioides. During the infectious process, fungal cells use several carbon sources, leading to the production of propionyl-CoA. The latter is metabolized by the methylcitrate synthase, a key enzyme of the methylcitrate cycle. We identified an inhibitor compound (ZINC08964784) that showed antifungal activity against P. brasiliensis. METHODS: This work aimed to understand the fungal metabolic response of P. brasiliensis cells exposed to ZINC08964784 through a proteomics approach. We used a glucose-free medium supplemented with propionate in order to simulate the environment found by the pathogen during the infection. We performed pyruvate dosage, proteolytic assay, dosage of intracellular lipids and quantification of reactive oxygen species in order to validate the proteomic results. RESULTS: The proteomic analysis indicated that the fungal cells undergo a metabolic shift due to the inhibition of the methylcitrate cycle and the generation of reactive species. Proteolytic enzymes were induced, driving amino acids into degradation for energy production. In addition, glycolysis and the citric acid cycle were down-regulated while ß-oxidation was up-regulated. The accumulation of pyruvate and propionyl-CoA led the cells to a state of oxidative stress in the presence of ZINC08964784. CONCLUSIONS: The inhibition of methylcitrate synthase caused by the compound promoted a metabolic shift in P. brasiliensis damaging energy production and generating oxidative stress. Hence, the compound is a promising alternative for developing new strategies of therapies against paracoccidioidomycosis.

Central and Effector Memory Human CD4+ and CD8+ T Cells during Cutaneous Leishmaniasis and after In Vitro Stimulation with Leishmania (Viannia) braziliensis Epitopes

Cutaneous Leishmaniasis (CL) is a Neglected Tropical Disease characterized by skin ulcers caused by Leishmania spp. protozoans and there is no safe and effective vaccine to reduce its negative consequences. In a previous work by our group, we identified T cell epitopes of Leishmania (Viannia) braziliensis which stimulated patients' T cells in vitro. In the present work, the peptides were tested as two pools for their ability to rescue memory T cells during natural infection by Leishmania. We analyzed the frequency of central memory (TCM, CD45RA-CD62L+) and effector memory (TEM, CD45RA + CD62L-) cells during active CL and post-treatment. In parallel, we investigated cell proliferation levels and the cytokines produced after stimulation. Interestingly, we observed higher frequencies (%) in CD4+ TEM during CL, and CD8+ TEM and CD8+ TCM during CL and post-treatment. Cell proliferation was increased, and a significant difference in expression was observed on T-bet and RORγT. Besides that, IFN-γ, IL-2, and IL-10 were detected in patient samples. Collectively, this dataset suggests that during CL there is an increase in the frequency of TCM and TEM, especially in the CD8 compartment. These results indicate a potentially immunogenic profile of the peptide pools, which can support the development of anti-Leishmania formulations.

Contributions of the institutions for the nursing professionalization: integrative review (2010-2020) in the light of freidsonian conceptions / Contribuciones de las entidades para la profesionalización de la enfermería: revisión integradora (2010-2020) bajo la luz de las concepciones freidsonianas / Contribuições das entidades para profissionalização da enfermagem: revisão integrativa (2010-2020) à luz das concepções freidsonianas

ABSTRACT Objective: To analyze the contributions of the Brazilian Nursing Association and the Federal and Regional Nursing Councils in the literature for the professionalization of nursing in the light of Eliot Freidson's theoretical conceptions. Methods: Integrative review of the literature, of socio-professional historical interest, carried out from June to November 2021, through the question: How did professional associations contribute to the professionalization of Brazilian nursing according to the literature from 2010 to 2020? The evidence were organized in a synoptic table, which allowed the construction of a conceptual map. Results: In the 23 selected studies, the professional associations presented scientific, social and political contributions, which shape the professional field of nursing, enabling knowledge/expertise, autonomy and self-regulation. Final considerations: The efforts of these institutions reaffirm nursing as an academic and consulting profession, capable of exerting control over the essence of nursing work. They strive to consolidate nursing as a legitimate professional field of health in Brazil.

RESUMEN Objetivo: Analizar las contribuciones de la Asociación Brasileña de Enfermería y de los Consejos Federales y Regionales de Enfermería a la profesionalización de la enfermería bajo la luz de las concepciones teóricas de Eliot Freidson Métodos: Se trata de una revisión integradora, de interés histórico socio profesional, realizada de junio a noviembre de 2021, mediante la pregunta: ¿Cómo han contribuido las entidades de clase con la profesionalización de la enfermería brasileña según la literatura de 2010 a 2020? Las pruebas se organizaron en un cuadro sinóptico que permitió construir un mapa conceptual. Resultados: En los 23 estudios seleccionados, las entidades de clase presentaron contribuciones científicas, sociales y políticas, que forman el campo profesional de la enfermería y facilitan el conocimiento, la experticia, la autonomía y la autorregulación. Consideraciones finales: Las entidades reafirman que la enfermería es una profesión académica y de consulta, capaz de ejercer el control sobre la esencia del trabajo en sí y perseveran para consolidarla como un campo profesional legítimo en el Brasil.

RESUMO Objetivo: Analisar na literatura contribuições da Associação Brasileira de Enfermagem e dos Conselhos Federal e Regionais de Enfermagem para a profissionalização da enfermagem à luz das concepções teóricas de Eliot Freidson. Métodos: Revisão integrativa, de interesse histórico socioprofissional, realizada de junho a novembro de 2021, mediante a questão: Como as entidades de classe contribuíram para a profissionalização da enfermagem brasileira de acordo com a literatura de 2010 a 2020? Organizaram-se as evidências em quadro sinótico, que possibilitou a construção de mapa conceitual. Resultados: Nos 23 estudos selecionados, as entidades de classe apresentaram contribuições científicas, sociais e políticas, que conformam o campo profissional da enfermagem, possibilitando conhecimento/expertise, autonomia e autorregulação. Considerações finais: Os esforços dessas entidades reafirmam a enfermagem como profissão acadêmica e de consulta, capaz de exercer controle sobre a essência do trabalho da enfermagem. Elas se empenham em consolidar a enfermagem como legítimo campo profissional da saúde no Brasil.

Proficiência digital e aprendizagem da história das entidades da enfermagem brasileira na pandemia / Competencia digital y aprendizaje de la historia de las asociaciones de enfermería brasileñas durante la pandemia / Digital proficiency and the learning of brazilian nursing institutions' history in the pandemic

Resumo Objetivo Caracterizar a proficiência digital e a aprendizagem de estudantes de enfermagem sobre a história das entidades de classe da enfermagem brasileira. Métodos Estudo exploratório-descritivo, transversal, realizado no curso de bacharelado em enfermagem, de três campi de uma instituição de ensino superior pública federal do Nordeste brasileiro. Aplicou-se, de novembro de 2020 a maio de 2021, questionário, via Google Forms, aos estudantes de enfermagem regularmente matriculados no segundo e terceiro períodos do curso. Realizou-se a análise estatística descritiva e inferencial. Resultados Participaram 56 estudantes de enfermagem, sendo 55,4% vinculados ao campus 1; 53,6% cursavam o terceiro semestre; 83,9% do sexo feminino; média idade de 20,55 (+3,32) anos; 55,4% pardos; 94,6% sem vínculo empregatício; 73,2% residindo com os pais; 92,9% com renda familiar mensal equivalente a três salários-mínimos. O grau de proficiência digital básico médio foi considerado baixo. Quanto às tecnologias digitais no ensino e à aprendizagem sobre história das entidades de classe, 62,5% acreditaram que contribuiria para aprendizagem, além do espaço da sala de aula, e facilitaria o acesso aos conteúdos; e 78,6% consideraram importante para desenvolver o senso crítico-reflexivo e a conscientização sobre a participação nessas entidades. Evidenciaram fundamental conhecer história da criação, contribuições, lutas, desafios e primeiras diretoras da Associação Brasileira de Enfermagem, além da criação dos Conselhos Federal e Regionais de Enfermagem e das respectivas atribuições. Conclusão As ações de ensino-aprendizagem, mediadas por tecnologias digitais, precisam considerar as competências digitais e os interesses dos estudantes na aprendizagem remota sobre história das entidades de classe da enfermagem.

Resumen Objetivo Caracterizar la competencia digital y el aprendizaje de estudiantes de enfermería sobre la historia de las asociaciones profesionales en la enfermería brasileña. Métodos Estudio exploratorio descriptivo, transversal, realizado en la carrera de licenciatura en enfermería, en tres campi de una institución de enseñanza superior pública federal del nordeste brasileño. De noviembre de 2020 a mayo de 2021, se aplicó un cuestionario por Google Forms a los estudiantes de enfermería regularmente matriculados en el segundo y tercer semestre de la carrera. Se realizó un análisis estadístico descriptivo e inferencial. Resultados Participaron 56 estudiantes de enfermería, el 55,4 % estaba vinculado al campus 1; el 53,6 % del tercer semestre; el 83,9 % de sexo femenino; promedio de edad de 20,55 (+3,32) años; el 55,4 % pardo; el 94,6 % sin vínculo laboral; el 73,2 % vive con sus padres; el 92,9 % con ingresos familiares mensuales equivalentes a tres salarios mínimos. El nivel de competencia digital básica promedio fue considerado bajo. En lo que se refiere a las tecnologías digitales en la enseñanza y al aprendizaje sobre historia de las asociaciones profesionales, el 62,5 % consideró que contribuiría para el aprendizaje, más allá del aula, y facilitaría el acceso a los contenidos; el 78,6 % lo consideró importante para desarrollar el sentido crítico-reflexivo y para concientizar sobre la participación en esas asociaciones. Consideraron fundamental conocer la historia de la creación, las contribuciones, las luchas, los desafíos y las primeras directoras de la Asociación Brasileña de Enfermería, además de la creación del Consejo Federal y los Consejos Regionales de Enfermería y sus respectivas atribuciones. Conclusión Las acciones de enseñanza-aprendizaje, mediadas por tecnologías digitales, deben considerar las competencias digitales y los intereses de los estudiantes en el aprendizaje remoto sobre historia de las asociaciones profesionales de enfermería.

Abstract Objective To characterize the digital proficiency of nurse students about the history of Brazilian nursing class institutions. Methods Exploratory-descriptive, cross-sectional study carried out in the Nursing bachelor's degree from three campuses of a federal public higher education institution in northeastern Brazil. We applied, from November 2020 to May, a questionnaire via Google Forms to nurse students regularly registered in the second and third periods of the course. We carried out statistical, descriptive, and inferential analyses. Results 56 nurse students participated in the study, of which 55.64% were from campus 1; 53.6% attended the third semester, 83.9% were female; average age of 20.55 (+3.32) years old; 55.4 were brown; 94.6% with no employment relationship; 73.2% living with their parents; 92.9% with a monthly family income of three minimum wages. We considered the average degree of basic digital proficiency low. Regarding the digital technologies in teaching and the learning about the class institutions' history, 62.5% believed that it contributed to the learning process, besides the classroom space and it eased the access to content, and 78.6% considered it important to develop a critical-reflexive sense and the awareness about the participation of these institutions. They found it fundamental to know the creation history, contributions, struggles, challenges, and first directors of the Brazilian Nursing Association, besides the creation of the Nursing Federal and Regional Councils and the respective attributions. Conclusion The teaching-learning process mediated by digital technologies needs to consider the digital competencies and students' interest in remote teaching about the nursing class institutions' history.

Turmeric supplementation with piperine is more effective than turmeric alone in attenuating oxidative stress and inflammation in hemodialysis patients: A randomized, double-blind clinical trial.

PURPOSE: Turmeric has renop rotective effects that can act to reduce oxidative stress and inflammation in hemodialysis (HD) patients. Piperine has been indicated as a bioavailability enhancer of turmeric and consequently of its biological effects. However, data on the efficacy of the turmeric/piperine combination in HD patients are limited. We aimed to verify whether turmeric supplementation in combination with piperine has a superior effect to turmeric alone in increasing antioxidant capacity and reducing oxidative stress and inflammation in HD patients. METHODS: This randomized, double-blind clinical trial was conducted in HD patients (age 20-75 years). Patients were supplemented with turmeric (3 g/day) or turmeric/piperine (3 g turmeric + 2 mg piperine/day) for 12 weeks. Malondialdehyde (MDA), antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), high-sensitivity C-reactive protein (hs-CRP), and ferritin were evaluated at baseline and the end of the study. RESULTS: There was a reduction in the MDA and ferritin levels in the turmeric/piperine group and in the comparison between groups at the end of the study [MDA: -0.08(-0.14/0.01) nmol/mL versus -0.003(-0.10/0.26) nmol/mL, p = 0.003; ferritin: -193.80 ±â€¯157.29 mg/mL versus 51.99 ±â€¯293.25 mg/mL, p = 0.018]. In addition, GPx activity reduced in the turmeric group (p = 0.029). No changes were observed for CAT, GR, and hs-CRP. CONCLUSION: Turmeric plus piperine was superior to turmeric alone in decreasing MDA and ferritin levels. The use of a combination of turmeric and piperine as a dietary intervention may be beneficial for modulating the status oxidative and inflammation in HD patients. BRAZILIAN REGISTRY OF CLINICAL TRIALS NUMBER: RBR-2t5zpd; Registration Date: May 2, 2018.