Aging-associated Alterations in the Gene Regulatory Network Landscape Associate with Risk, Prognosis and Response to Therapy in Lung Adenocarcinoma.

Aging is the primary risk factor for many individual cancer types, including lung adenocarcinoma (LUAD). To understand how aging-related alterations in the regulation of key cellular processes might affect LUAD risk and survival outcomes, we built individual (person)-specific gene regulatory networks integrating gene expression, transcription factor protein-protein interaction, and sequence motif data, using PANDA/LIONESS algorithms, for both non-cancerous lung tissue samples from the Genotype Tissue Expression (GTEx) project and LUAD samples from The Cancer Genome Atlas (TCGA). In GTEx, we found that pathways involved in cell proliferation and immune response are increasingly targeted by regulatory transcription factors with age; these aging-associated alterations are accelerated by tobacco smoking and resemble oncogenic shifts in the regulatory landscape observed in LUAD and suggests that dysregulation of aging pathways might be associated with an increased risk of LUAD. Comparing normal adjacent samples from individuals with LUAD with healthy lung tissue samples from those without LUAD, we found that aging-associated genes show greater aging-biased targeting patterns in younger individuals with LUAD compared to their healthy counterparts of similar age, a pattern suggestive of age acceleration. This implies that an accelerated aging process may be responsible for tumor incidence in younger individuals. Using drug repurposing tool CLUEreg, we found small molecule drugs with potential geroprotective effects that may alter the accelerating aging profiles we found. We also observed that, in contrast to chronological age, a network-informed aging signature was associated with survival and response to chemotherapy in LUAD.

Characterization of parameters for the analysis of objective measures of non-nutritive sucking of newborns. / Caracterização de parâmetros para análise de medidas objetivas da sucção não-nutritiva de recém-nascidos.

PURPOSE: To propose a methodology for analyzing data generated by an instrument measuring non-nutritive sucking pressure in newborns. METHODS: An analytical observational study was developed, with a cross-sectional design, considering the data collected from 24 full-term newborns without complications. Three collections from each neonate were analyzed, with duration of 2 minutes and a 2-minute interval between them. The defined parameters were extracted using a program developed in Matlab®. The results were obtained by analyzing and comparing 12 variables at a 5% confidence level. Comparison of manual and computerized analyzes was also carried out using the intraclass correlation coefficient. RESULTS: The multiple comparison between the three collection moments showed that the significant statistical differences occurred between collections one and two and two and three. When analyzing and comparing each variable separately, it was noted that the second collection showed: greater number of sucking groups, greater number of suctions, less time to start the sucking groups, longer time of sucking groups, less number of sporadic suctions, higher mean pressure values and with less standard deviation, more number of pauses with shorter time of pauses. The intraclass correlation coefficient revealed almost perfect agreement for the 12 evaluated parameters. CONCLUSION: The 12 variables analyzed are relevant, especially in the second collection. The Matlab® program proved to be viable and effective in extracting and analyzing parameters, showing high agreement when compared to manual evaluation.

OBJETIVO: Propor uma metodologia de análise dos dados gerados por um instrumento de medição da pressão de sucção não-nutritiva do recém-nascido. MÉTODO: Estudo observacional analítico, transversal com dados de 24 recém-nascidos a termo sem comprometimentos. Após a avaliação clínica foram analisadas três coletas de cada neonato empregando-se o referido instrumento, com duração de 2 minutos e intervalo de 2 minutos entre elas. Os parâmetros definidos foram extraídos por meio de um programa desenvolvido em Matlab®. Os resultados foram obtidos pela análise e comparação de 12 variáveis ao nível de confiança de 5%. Foi realizada ainda comparação das análises manual e computadorizada por meio do coeficiente de correlação intraclasse. RESULTADOS: A comparação múltipla entre os três momentos de coleta, mostrou que as diferenças estatísticas significantes ocorreram entre as coletas um e dois e dois e três. Ao se analisar e comparar cada variável separadamente, notou-se que a segunda coleta apresentou: maior número de grupos de sucção, maior número de sucções, menor tempo para iniciar os grupos de sucção, maior tempo de grupos de sucção, menor número de sucções esporádicas, valores de pressão média maiores e com menor desvio padrão, maior número de pausas com tempo de pausas menor. O coeficiente de correlação intraclasse revelou concordância quase perfeita para os 12 parâmetros avaliados. CONCLUSÃO: As 12 variáveis analisadas mostram-se relevantes, especialmente na segunda coleta. O programa em Matlab® mostrou-se viável e eficaz na extração e análise dos parâmetros, apresentando alta concordância quando comparado à avaliação manual.

Spatially distinct epithelial and mesenchymal cell subsets along progressive lineage restriction in the branching embryonic mammary gland.

How cells coordinate morphogenetic cues and fate specification during development remains a fundamental question in organogenesis. The mammary gland arises from multipotent stem cells (MaSCs), which are progressively replaced by unipotent progenitors by birth. However, the lack of specific markers for early fate specification has prevented the delineation of the features and spatial localization of MaSC-derived lineage-committed progenitors. Here, using single-cell RNA sequencing from E13.5 to birth, we produced an atlas of matched mouse mammary epithelium and mesenchyme and reconstructed the differentiation trajectories of MaSCs toward basal and luminal fate. We show that murine MaSCs exhibit lineage commitment just prior to the first sprouting events of mammary branching morphogenesis at E15.5. We identify early molecular markers for committed and multipotent MaSCs and define their spatial distribution within the developing tissue. Furthermore, we show that the mammary embryonic mesenchyme is composed of two spatially restricted cell populations, and that dermal mesenchyme-produced FGF10 is essential for embryonic mammary branching morphogenesis. Altogether, our data elucidate the spatiotemporal signals underlying lineage specification of multipotent MaSCs, and uncover the signals from mesenchymal cells that guide mammary branching morphogenesis.

Thiazolyl-isatin derivatives: Synthesis, in silico studies, in vitro biological profile against breast cancer cells, mRNA expression, P-gp modulation, and interactions of Akt2 and VIM proteins.

The literature reports that thiazole and isatin nuclei present a range of biological activities, with an emphasis on anticancer activity. Therefore, our proposal was to make a series of compounds using the molecular hybridization strategy, which has been used by our research group, producing hybrid molecules containing the thiazole and isatin nuclei. After structural planning and synthesis, the compounds were characterized and evaluated in vitro against breast cancer cell lines (T-47D, MCF-7 and MDA-MB-231) and against normal cells (PBMC). The activity profile on membrane proteins involved in chemoresistance and tumorigenic signaling proteins was also evaluated. Among the compounds tested, the compounds 4c and 4a stood out with IC50 values of 1.23 and 1.39 µM, respectively, against the MDA-MB-231 cell line. Both compounds exhibited IC50 values of 0.45 µM for the MCF-7 cell line. Compounds 4a and 4c significantly decreased P-gp mRNA expression levels in MCF-7, 4 and 2 folds respectively. Regarding the impact on tumorigenic signaling proteins, compound 4a inhibited Akt2 in MDA-MB-231 and compound 4c inhibited the mRNA expression of VIM in MCF-7.

Caracterização de parâmetros para análise de medidas objetivas da sucção não-nutritiva de recém-nascidos / Characterization of parameters for the analysis of objective measures of non-nutritive sucking of newborns

RESUMO Objetivo Propor uma metodologia de análise dos dados gerados por um instrumento de medição da pressão de sucção não-nutritiva do recém-nascido. Método Estudo observacional analítico, transversal com dados de 24 recém-nascidos a termo sem comprometimentos. Após a avaliação clínica foram analisadas três coletas de cada neonato empregando-se o referido instrumento, com duração de 2 minutos e intervalo de 2 minutos entre elas. Os parâmetros definidos foram extraídos por meio de um programa desenvolvido em Matlab®. Os resultados foram obtidos pela análise e comparação de 12 variáveis ao nível de confiança de 5%. Foi realizada ainda comparação das análises manual e computadorizada por meio do coeficiente de correlação intraclasse. Resultados A comparação múltipla entre os três momentos de coleta, mostrou que as diferenças estatísticas significantes ocorreram entre as coletas um e dois e dois e três. Ao se analisar e comparar cada variável separadamente, notou-se que a segunda coleta apresentou: maior número de grupos de sucção, maior número de sucções, menor tempo para iniciar os grupos de sucção, maior tempo de grupos de sucção, menor número de sucções esporádicas, valores de pressão média maiores e com menor desvio padrão, maior número de pausas com tempo de pausas menor. O coeficiente de correlação intraclasse revelou concordância quase perfeita para os 12 parâmetros avaliados. Conclusão As 12 variáveis analisadas mostram-se relevantes, especialmente na segunda coleta. O programa em Matlab® mostrou-se viável e eficaz na extração e análise dos parâmetros, apresentando alta concordância quando comparado à avaliação manual.

ABSTRACT Purpose To propose a methodology for analyzing data generated by an instrument measuring non-nutritive sucking pressure in newborns. Methods An analytical observational study was developed, with a cross-sectional design, considering the data collected from 24 full-term newborns without complications. Three collections from each neonate were analyzed, with duration of 2 minutes and a 2-minute interval between them. The defined parameters were extracted using a program developed in Matlab®. The results were obtained by analyzing and comparing 12 variables at a 5% confidence level. Comparison of manual and computerized analyzes was also carried out using the intraclass correlation coefficient. Results The multiple comparison between the three collection moments showed that the significant statistical differences occurred between collections one and two and two and three. When analyzing and comparing each variable separately, it was noted that the second collection showed: greater number of sucking groups, greater number of suctions, less time to start the sucking groups, longer time of sucking groups, less number of sporadic suctions, higher mean pressure values and with less standard deviation, more number of pauses with shorter time of pauses. The intraclass correlation coefficient revealed almost perfect agreement for the 12 evaluated parameters. Conclusion The 12 variables analyzed are relevant, especially in the second collection. The Matlab® program proved to be viable and effective in extracting and analyzing parameters, showing high agreement when compared to manual evaluation.

Bayesian Optimized sample-specific Networks Obtained By Omics data (BONOBO).

Gene regulatory networks (GRNs) are effective tools for inferring complex interactions between molecules that regulate biological processes and hence can provide insights into drivers of biological systems. Inferring co-expression networks is a critical element of GRN inference as the correlation between expression patterns may indicate that genes are coregulated by common factors. However, methods that estimate co-expression networks generally derive an aggregate network representing the mean regulatory properties of the population and so fail to fully capture population heterogeneity. To address these concerns, we introduce BONOBO (Bayesian Optimized Networks Obtained By assimilating Omics data), a scalable Bayesian model for deriving individual sample-specific co-expression networks by recognizing variations in molecular interactions across individuals. For every sample, BONOBO assumes a Gaussian distribution on the log-transformed centered gene expression and a conjugate prior distribution on the sample-specific co-expression matrix constructed from all other samples in the data. Combining the sample-specific gene expression with the prior distribution, BONOBO yields a closed-form solution for the posterior distribution of the sample-specific co-expression matrices, thus making the method extremely scalable. We demonstrate the utility of BONOBO in several contexts, including analyzing gene regulation in yeast transcription factor knockout studies, prognostic significance of miRNA-mRNA interaction in human breast cancer subtypes, and sex differences in gene regulation within human thyroid tissue. We find that BONOBO outperforms other sample-specific co-expression network inference methods and provides insight into individual differences in the drivers of biological processes.

Gene regulatory Networks Reveal Sex Difference in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response to therapy. However, the molecular mechanisms responsible for these disparities have not been investigated extensively. Sample-specific gene regulatory network methods were used to analyze RNA sequencing data from non-cancerous human lung samples from The Genotype Tissue Expression Project (GTEx) and lung adenocarcinoma primary tumor samples from The Cancer Genome Atlas (TCGA); results were validated on independent data. We observe that genes associated with key biological pathways including cell proliferation, immune response and drug metabolism are differentially regulated between males and females in both healthy lung tissue, as well as in tumor, and that these regulatory differences are further perturbed by tobacco smoking. We also uncovered significant sex bias in transcription factor targeting patterns of clinically actionable oncogenes and tumor suppressor genes, including AKT2 and KRAS. Using differentially regulated genes between healthy and tumor samples in conjunction with a drug repurposing tool, we identified several small-molecule drugs that might have sex-biased efficacy as cancer therapeutics and further validated this observation using an independent cell line database. These findings underscore the importance of including sex as a biological variable and considering gene regulatory processes in developing strategies for disease prevention and management.

Adjustment of spurious correlations in co-expression measurements from RNA-Sequencing data.

MOTIVATION: Gene co-expression measurements are widely used in computational biology to identify coordinated expression patterns across a group of samples. Coordinated expression of genes may indicate that they are controlled by the same transcriptional regulatory program, or involved in common biological processes. Gene co-expression is generally estimated from RNA-Sequencing data, which are commonly normalized to remove technical variability. Here, we demonstrate that certain normalization methods, in particular quantile-based methods, can introduce false-positive associations between genes. These false-positive associations can consequently hamper downstream co-expression network analysis. Quantile-based normalization can, however, be extremely powerful. In particular, when preprocessing large-scale heterogeneous data, quantile-based normalization methods such as smooth quantile normalization can be applied to remove technical variability while maintaining global differences in expression for samples with different biological attributes. RESULTS: We developed SNAIL (Smooth-quantile Normalization Adaptation for the Inference of co-expression Links), a normalization method based on smooth quantile normalization specifically designed for modeling of co-expression measurements. We show that SNAIL avoids formation of false-positive associations in co-expression as well as in downstream network analyses. Using SNAIL, one can avoid arbitrary gene filtering and retain associations to genes that only express in small subgroups of samples. This highlights the method's potential future impact on network modeling and other association-based approaches in large-scale heterogeneous data. AVAILABILITY AND IMPLEMENTATION: The implementation of the SNAIL algorithm and code to reproduce the analyses described in this work can be found in the GitHub repository https://github.com/kuijjerlab/PySNAIL.

Short-chain fatty acids are associated with adiposity, energy and glucose homeostasis among different metabolic phenotypes in the Nutritionists' Health Study.

BACKGROUND AND AIMS: The gut microbiome is associated with obesity, mainly mediated by bacteria-produced short-chain fatty acids (SCFAs). It is unknown how SCFA concentrations are associated with the phenotypes metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese/overweight (MHO), and metabolically unhealthy obese/overweight (MUO). We compared plasma and fecal SCFA concentrations among adult women categorized according to the metabolic phenotypes mentioned above and examined associations between SCFA and adiposity and components of energy and glucose homeostasis. METHODS: This was a cross-sectional study involving 111 participants. Body composition was assessed by DEXA. Energy and glycemic homeostasis were assessed by the standard mixed-meal tolerance test coupled with indirect calorimetry. SCFAs were quantified by gas chromatography and mass spectrometry. RESULTS: Only plasma propionate was increased in the MHNW phenotype compared to the MHO and MUO phenotypes [p < 0.05]. Fecal propionate and butyrate concentrations and plasma propionate concentrations were inversely associated with total and visceral adiposity [p < 0.05]. Fecal and plasma SCFA concentrations were associated with reduced glucose, insulin and HbA1c levels, increased fasting and postprandial GLP-1 levels; and more preserved beta-cell function [p < 0.05]. Fecal and plasma SCFA concentrations were positively correlated with resting energy expenditure and lipid oxidation rate and inversely correlated with the oxidation rate of carbohydrates [p < 0.05]. CONCLUSION: These findings reinforce the concept that fecal and plasma SCFA concentrations are linked to specific components of energy and glucose homeostasis; and body adiposity. However, it was not possible to discriminate the different metabolic phenotypes of adiposity based on the determination of fecal SCFA concentrations.

The Network Zoo: a multilingual package for the inference and analysis of gene regulatory networks.

Inference and analysis of gene regulatory networks (GRNs) require software that integrates multi-omic data from various sources. The Network Zoo (netZoo; netzoo.github.io) is a collection of open-source methods to infer GRNs, conduct differential network analyses, estimate community structure, and explore the transitions between biological states. The netZoo builds on our ongoing development of network methods, harmonizing the implementations in various computing languages and between methods to allow better integration of these tools into analytical pipelines. We demonstrate the utility using multi-omic data from the Cancer Cell Line Encyclopedia. We will continue to expand the netZoo to incorporate additional methods.

X chromosome associations with chronic obstructive pulmonary disease and related phenotypes: an X chromosome-wide association study.

BACKGROUND: The association between genetic variants on the X chromosome to risk of COPD has not been fully explored. We hypothesize that the X chromosome harbors variants important in determining risk of COPD related phenotypes and may drive sex differences in COPD manifestations. METHODS: Using X chromosome data from three COPD-enriched cohorts of adult smokers, we performed X chromosome specific quality control, imputation, and testing for association with COPD case-control status, lung function, and quantitative emphysema. Analyses were performed among all subjects, then stratified by sex, and subsequently combined in meta-analyses. RESULTS: Among 10,193 subjects of non-Hispanic white or European ancestry, a variant near TMSB4X, rs5979771, reached genome-wide significance for association with lung function measured by FEV1/FVC ([Formula: see text] 0.020, SE 0.004, p 4.97 × 10-08), with suggestive evidence of association with FEV1 ([Formula: see text] 0.092, SE 0.018, p 3.40 × 10-07). Sex-stratified analyses revealed X chromosome variants that were differentially trending in one sex, with significantly different effect sizes or directions. CONCLUSIONS: This investigation identified loci influencing lung function, COPD, and emphysema in a comprehensive genetic association meta-analysis of X chromosome genetic markers from multiple COPD-related datasets. Sex differences play an important role in the pathobiology of complex lung disease, including X chromosome variants that demonstrate differential effects by sex and variants that may be relevant through escape from X chromosome inactivation. Comprehensive interrogation of the X chromosome to better understand genetic control of COPD and lung function is important to further understanding of disease pathology. Trial registration Genetic Epidemiology of COPD Study (COPDGene) is registered at ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008). Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints Study (ECLIPSE), GlaxoSmithKline study code SCO104960, is registered at ClinicalTrials.gov, NCT00292552 (Active since February 16, 2006). Genetics of COPD in Norway Study (GenKOLS) holds GlaxoSmithKline study code RES11080, Genetics of Chronic Obstructive Lung Disease.

Epidemiology of tobacco use and nicotine dependence in truck drivers.

OBJECTIVE: To investigate the epidemiology of tobacco use and nicotine dependence in a sample of truck drivers in Brazil. METHODS: Between 2015 and 2016, a cross-sectional study was conducted on 624 truck drivers who operate on the BR-050 highway in Brazil. Participants were interviewed about sociodemographic data, occupational characteristics, mental health, behavioral data, and tobacco use. Then, the Fagerstrom test for nicotine dependence (FTND) was used to verify nicotine dependence in smoking truck drivers. Logistic regression and linear regression were also used to verify factors associated with tobacco use in the previous 30 days and nicotine dependence scores, respectively. RESULTS: The prevalence of tobacco use among truck drivers was 21.1% (n = 132;95%CI: 18.1-24.5). Of the total number of smokers who responded to the FTND (n = 118; 89.4%), most had high/very high nicotinic dependence (68.6%; 95%CI: 59.8-76.3). Tobacco use was associated with absence of religion (adjusted odds ratio [AOR]: 2.60; 95%CI: 1.35-5.01), employment relationship of the contract (AOR = 1.98; 95%CI: 1.26-3.13); > 12 hours daily working time (AOR = 1.80; 95%CI: 1.09-2.98) and alcohol use in the previous 30 days (AOR = 2.92; 95%CI: 1.86-4.57). Irregular physical activity was associated with higher scores of nicotine dependence (ß = 1.87; 95%CI: 0.55-3.19). CONCLUSION: The results showed a high prevalence of tobacco use and high/very high nicotine dependence among the truck drivers.

Short-term flaxseed oil, rich in omega 3, protects mice against metabolic damage caused by high-fat diet, but not inflammation.

It is known that long-term high-fat diet (HF) feeding drastically affects the adipose tissue, contributing to metabolic disorders. Recently, short-term HF consumption was shown to affect different neuronal signaling pathways. Thus, we aimed to evaluate the inflammatory effects of a short-term HF and whether a diet containing omega-3 fatty acid fats from flaxseed oil (FS) has protective effects. Mice were divided into three groups for 3 d, according to their diets: Control group (CT), HF, or FS for 3 d. Lipid profiles were assessed through mass spectrometry and inflammatory markers by RT-qPCR and Western blotting. After short-term HF, mice increased food intake, body weight, adiposity, and fasting glucose. Increased mRNA content of Ccl2 and Tnf was demonstrated in the HF compared to CT in mesenteric adipose tissue. In the liver, TNFα protein was higher in the HF group than in CT, followed by a decreased polyunsaturated fatty acids tissue incorporation in HF. On the other hand, the consumption of FS reduced food intake and fasting glucose, as well as increased omega-3 fatty acid incorporation in MAT and the liver. However, short-term FS was insufficient to control the early inflammation triggered by HF in MAT and the liver. These data demonstrated that a 3-d HF diet is enough to damage glucose homeostasis and trigger inflammation. In contrast, short-term FS protects against increased food intake and fasting glucose but not inflammation in mice.

Depression, health status and life satisfaction in voice hearers / Depressão, estado de saúde e satisfação de vida em ouvidores de vozes

Objective: The objective of this study was to review the occurrence of depressive episodes and their relationship with the health status and life satisfaction in patients who hear voices. Methods: This is a cross-sectional study carried out between February and March 2019. For data collection, a questionnaire was used on socioeconomic and health conditions as well as the Beck's Depression Inventory and Life Satisfaction Scale. The database was elaborated in the Epidata program and the analysis in Stata 11. Results: A total of 112 patients participated in the survey; 82 answered all the questions in Beck's inventory. Patients who reported that they considered their health as very bad or bad and those who had high blood pressure experienced depression. Poor life satisfaction was also associated with the presence of depressive symptoms. Conclusion: It is therefore evident the importance of considering such aspects in the health care of voice-hearers.

Objetivo: O objetivo deste estudo foi analisar a ocorrência de episódios depressivos e sua relação com estado de saúde e satisfação de vida em usuários ouvidores de vozes. Método: Trata-se de um estudo transversal realizado entre fevereiro e março de 2019. Para coleta de dados utilizou-se um questionário com questões socioeconômicas, condições de saúde, Inventário de Depressão de Beck e Escala de Satisfação com a Vida. O banco de dados foi elaborado no programa Epidata e a análise no Stata 11. Resultados: Participaram da pesquisa 112 usuários, sendo que 82 responderam todas as questões do inventário de Beck. Os usuários que referiram considerar sua saúde como péssima/ruim e aqueles que possuíam hipertensão arterial apresentaram depressão. Além disso, a baixa satisfação com a vida também foi associada com a presença de sintomas depressivos. Conclusão: Diante disso, evidencia-se a importância de se considerar esses aspectos no cuidado à saúde de ouvidores de vozes.

Atividades grupais na perspectiva de enfermeiros da Atenção Psicossocial / Group activities from the perspective of Psychosocial Care nurses / Actividades grupales desde la perspectiva de las enfermeras de Atención Psicosocial

O estudo teve como objetivo compreender as atividades grupais na perspectiva de enfermeiros dos Centros de Atenção Psicossocial. Trata-se de uma pesquisa qualitativa e descritiva realizada com 15 enfermeiros atuantes nos serviços. A entrevista discursiva foi o instrumento utilizado. Realizou-se a Análise Temática de Minayo e utilizou-se a teoria de Pichon-Rivière sobre grupos operativos, em diálogo com outras investigações, para orientar a interpretação dos dados. Entre os aspectos apontados pelos enfermeiros estão: a pouca formação para atuar na coordenação de grupo; a falta de incentivo institucional para que possam se especializar; a superlotação dos grupos e a pouca disponibilidade de estrutura física e de recursos materiais. Entende-se que uma das principais formas de enfrentar os desafios apontados é a apropriação, por parte dos profissionais, de um aporte teórico para trabalhar com grupos, o qual pode ser balizado pela prática da educação permanente em saúde nos serviços.

The study aimed to understand group activities from the perspective of nurses from Psychosocial Care Centers. This is a qualitative descriptive research conducted with 15 nurses working in the services. The discursive interview was the instrument used. Thematic analysis from Minayo was carried out and the Pichon-Rivière theory on operative groups was used in dialogue with other investigations to guide the interpretation of the data. Among the aspects pointed out by nurses, there is little training to work in group coordination; the lack of institutional incentive for them to specialize; overcrowding of groups; and the limited availability of physical structure and material resources. It is understood that one of the main ways to face the challenges mentioned is the appropriation by professionals of a theoretical framework to work with groups, which can be guided by the practice of permanent education in health services.

El estudio tuvo como objetivo comprender las actividades grupales desde la perspectiva de los enfermeros de los Centros de Atención Psicosocial. Esta es una investigación descriptiva cualitativa realizada con 15 enfermeras que laboran en los servicios. La entrevista oral fue el instrumento utilizado. Se realizó el análisis temático de Minayo y se utilizó la teoría de Pichon-Rivière sobre grupos operativos en diálogo con otras investigaciones para orientar la interpretación de los datos. Entre los aspectos señalados por las enfermeras se encuentra la falta de capacitación para trabajar en coordinación grupal; la falta de incentivo institucional para que se especialicen; hacinamiento de grupos; y la disponibilidad limitada de estructura física y recursos materiales. Se entiende que una de las principales formas de afrontar los retos mencionados es la apropiación por parte de los profesionales de un marco teórico para trabajar con grupos, el cual puede ser guiado por la práctica de la educación permanente en salud en los servicios.

IL-7 Receptor Drives Early T Lineage Progenitor Expansion.

IL-7 and IL-7R are essential for T lymphocyte differentiation by driving proliferation and survival of specific developmental stages. Although early T lineage progenitors (ETPs), the most immature thymocyte population known, have a history of IL-7R expression, it is unclear whether IL-7R is required at this stage. In this study, we show that mice lacking IL-7 or IL-7R have a marked loss of ETPs that results mostly from a cell-autonomous defect in proliferation and survival, although no changes were detected in Bcl2 protein levels. Furthermore, a fraction of ETPs responded to IL-7 stimulation ex vivo by phosphorylating Stat5, and IL-7R was enriched in the most immature Flt3+Ccr9+ ETPs. Consistently, IL-7 promoted the expansion of Flt3+ but not Flt3- ETPs on OP9-DLL4 cocultures, without affecting differentiation at either stage. Taken together, our data show that IL-7/IL-7R is necessary following thymus seeding by promoting proliferation and survival of the most immature thymocytes.

Entrevista fenomenológica como ferramenta de pesquisa em enfermagem: reflexão teórica / Entrevista fenomenológica como herramienta de investigación en enfermería: reflexión teórica / Phenomenological interview as a research tool in nursing: theoretical reflection

Objetivo: Refletir acerca da utilização da entrevista fenomenológica no desvelamento do fenômeno em pesquisas da enfermagem. Metodologia: Estudo teórico reflexivo à luz do referencial teórico filosófico e metodológico de Martin Heidegger, proposto a analisar os aspectos contextuais da entrevista fenomenológica em pesquisas da enfermagem. Resultado: Este recurso metodológico, em pesquisa qualitativa, proporciona o estar com o outro de forma ampliada na busca da singularidade de cada ser indo em direção a clarificação do fenômeno vivido. Conclusão: Para a enfermagem, a entrevista fenomenológica visa contribuir para a compreensão do ser em suas relações com o mundo, promovendo maior visibilidade deste e proporcionando importante contribuição para o desvelamento do fenômeno investigado nas pesquisas de abordagem fenomenológica

Objective: To reflect on the use of phenomenological interviews in the unveiling of the phenomenon in nursing research. Methodology: Reflective theoretical study in the lightof Martin Heidegger's philosophical and methodological theoretical framework, proposed to analyze the contextual aspects of phenomenological interviews in nursing research. Result: In qualitative research, this methodological resource provides the being-with-the-other in an expanded way in the search for the singularity of each being, in order to clarify the phenomenon experienced. Conclusion: For nursing, phenomenological interviews aim at contributing to the understanding of the being in their relationships with the world, promoting greater visibility of the world and providing an important contribution to the unveiling of the phenomenon investigated in phenomenological approach research.

Objetivo: Reflexionar sobre el uso de la entrevista fenomenológica para develar el fenómeno en la investigación en enfermería. Metodología: Estudio teórico reflexivo a la luz del marco teórico filosófico y metodológico de Martin Heidegger, propuesto para analizarlos aspectos contextuales de la entrevista fenomenológica em la investigación em enfermería. Resultado: Este recurso metodológico, en la investigación cualitativa, proporciona el ser conelotro de manera expandida em la búsqueda de la singularidad de cada ser, a fin de aclarar el fenómeno experimentado. Conclusión: Para la enfermería, la entrevista fenomenológica tiene como objetivo contribuir a la comprensión de estar en sus relaciones com el mundo, promover una mayor visibilidade del mundo y proporcionar una contribución importante a la revelacion del fenómeno investigado em la investigación de enfoque fenomenológico

Acute Outcomes of Cigarette Smoke and Electronic Cigarette Aerosol Inhalation in a Murine Model.

Cigarette smoking throughout life causes serious health issues in the lungs. The electronic cigarette (E-Cig) use increased, since it was first introduced in the world. This research work compared the short-term exposure consequences to e-cigarette vapor and cigarette smoke in male mice. Forty-five C57BL/6 mice were randomized into control (C) in an ambient air exposition cigarette smoke (CS) and aerosol electronic cigarette (EC), both were exposed to 120 puffs, 3 times/day during five days. Then, in the experimental protocol, the euthanized mice had their tissues removed for analysis. Our study showed that CS and EC resulted in higher cell influx into the airways, and an increase in macrophage counts in CS (209.25 ± 7.41) and EC (220.32 ± 8.15) when compared to C (108.40 ± 4.49) (p < 0.0001). The CS (1.92 ± 0.23) displayed a higher pulmonary lipid peroxidation as opposed to C (0.93 ± 0.06) and EC (1.23 ± 0.17) (p < 0.05). The EC (282.30 ± 25.68) and CS (368.50 ± 38.05) promoted increased levels of interleukin 17 when compared to C (177.20 ± 10.49) (p < 0.05). The EC developed shifts in lung histoarchitecture, characterized by a higher volume density in the alveolar air space (60.21; 55.00-65.83) related to C (51.25; 18.75-68.75) and CS (50.26; 43.75-62.08) (p =0.002). The EC (185.6 ± 9.01) presented a higher respiratory rate related to CS (133.6 ± 10.2) (p < 0.002). Therefore, our findings demonstrated that the short-term exposure to e-cig promoted more acute inflammation comparing to cigarette smoke in the ventilatory parameters of the animals.

Psicotrópicos: uso por estudantes universitários antes e durante a pandemia de doença por coronavírus 2019 / Psicotrópicos: uso por estudiantes universitarios antes y durante la pandemia de enfermedad del coronavirus 2019 / Psychotropics: use by college students before and during the coronavirus disease 2019 pandemic

Objetivo: descrever a utilização de psicotrópicos por estudantes universitários antes e durante a pandemia de doença por coronavírus 2019. Métodos: estudo transversal com 464 estudantes que frequentaram uma disciplina ofertada durante a pandemia. Utilizou-se um questionário via Google Forms com questões autoaplicáveis. As informações coletadas foram transferidas para o Microsoft Excel 2007 e analisadas no software Statistical Package for the Social Sciences 25.0. Resultado: 37,3% referiram fazer uso de psicotrópicos antes ou durante a pandemia. Destes, mais de 80,0% relataram fazer uso antes e 17,5% iniciaram após o início da pandemia, sendo a maioria do sexo feminino, solteiras e cursando o primeiro ou o último semestre da graduação. Os antidepressivos foram os mais utilizados pelos participantes (64,0%). Conclusões: a prevalência do uso de psicotrópicos entre estudantes pode ter se acentuado na pandemia. O desenvolvimento de programas e políticas voltadas à promoção e cuidado à saúde mental dos universitários é necessário.(AU)

Objective: to describe the use of psychotropic drugs by university students before and during the 2019 coronavirus disease pandemic. Method: cross-sectional study with 464 students who attended a course offered during the pandemic. A questionnaire was used via Google Forms with self- administered questions. The collected information was transferred to the Microsoft Excel 2007 and analyzed in the Statistical Package for the Social Sciences 25.0 software. Result: 37.3% reported using psychotropic drugs before or during the pandemic. Of these, more than 80.0% reported using it before and 17.5% started after the beginning of the pandemic, the majority being female, single, and attending the first or last semester of graduation. Antidepressants were the most used by participants (64.0%). Conclusions: the prevalence of psychotropic use among students may have increased during the pandemic. The development of programs and policies aimed at promoting and caring for the mental health of university students is necessary.(AU)

Objetivo: describir el uso de psicofármacos por parte de estudiantes universitarios antes y durante la pandemia de la enfermedad por coronavirus 2019. Método: estudio transversal con 464 estudiantes que asistieron un curso ofrecido durante la pandemia. Se utilizó un cuestionario en Google Forms con preguntas autoadministradas. La información recolectada fue transferida al Microsoft Excel 2007 y analizada en el software Statistical Package for the Social Sciences 25.0. Resultado: el 37,3% informó usar psicofármacos antes o durante la pandemia. De estos, más del 80,0% reportaron usarlo antes y el 17,5% iniciaron después, siendo la mayoría mujeres, solteras y cursando el primer o último semestre de graduación. Los antidepresivos fueron los más utilizados por los participantes (64,0%). Conclusiones: la prevalencia del consumo de psicotrópicos entre estudiantes puede haber aumentado durante la pandemia. Es necesario el desarrollo de programas y políticas dirigidas a promover y cuidar la salud mental de estudiantes universitarios.(AU)

Alterações de vida e saúde em adultos em decorrência do período de isolamento social durante a pandemia da COVID-19: estudo transversal / Changes in life and health in adults as a result of the period of social isolation during the COVID-19 pandemic: cross-sectional study

Introdução: A pandemia da COVID-19 trouxe à população mundial mudanças de vidas em diferentes áreas. Objetivo: Descrever as principais alterações de vida e saúde de adultos em decorrência do período de isolamento social vivido pela pandemia da COVID-19. Métodos: Trata-se de um estudo transversal, descritivo e quantitativo com 412 indivíduos, de ambos os sexos, idade entre 18 e 49 anos, submetidos a um questionário virtual sobre as alterações de vida e saúde no período de isolamento social do Estado Pernambuco/PE. Resultados: A maioria dos participantes foram do sexo feminino, com idade média de 26,18 anos, afirmando ter problemas com o isolamento social, precisando se adaptar a uma nova realidade sobre hábitos alimentares, higiênicos e atividade física. O isolamento social consequência da pandemia desencadeou, na maioria dos participantes deste estudo, sintomas como ansiedade, estresse, medo, angústia, tontura, dores musculares, principalmente na coluna e dores articulares, princilamente nos joelhos. Conclusão: O isolamento social em decorrência da pandemia pela COVID-19 pode afetar tanto a vida e saúde das pessoas, pode desencadear doenças psicoemocionais e dificultar o processo de adaptação social.