Validation of Induced Microglia-Like Cells (iMG Cells) for Future Studies of Brain Diseases

Microglia are the primary resident immune cells of the central nervous system that maintain physiological homeostasis in the brain and contribute to the pathogenesis of many psychiatric disorders and neurodegenerative diseases. Due to the lack of appropriate human cellular models, it is difficult to study the basic pathophysiological processes linking microglia to brain diseases. In this study, we adopted a microglia-like cellular model derived from peripheral blood monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-34 (IL-34). We characterized and validated this in vitro cellular model by morphology, immunocytochemistry, gene expression profiles, and functional study. Our results indicated that the iMG cells developed typical microglial ramified morphology, expressed microglial specific surface markers (P2RY12 and TMEM119), and possessed phagocytic activity. Principal component analyses and multidimensional scaling analyses of RNA-seq data showed that iMG cells were distinct from monocytes and induced macrophages (iMacs) but clustered closer to human microglia and hiPSC-induced microglia. Heatmap analyses also found that iMG cells, but not monocytes, were closely clustered with human primary microglia. Further pathway and relative expression analysis indicated that unique genes from iMG cells were involved in the regulation of the complement system, especially in the synapse and ion transport. Overall, our data demonstrated that the iMG model mimicked many features of the brain resident microglia, highlighting its utility in the study of microglial function in many brain diseases, such as schizophrenia and Alzheimer\u27s disease (AD)

EDUCAÇÃO ESTADUAL: PROJETO CRIANDO OPORTUNIDADES – REFORÇO ESCOLAR

Visando apresentar uma política pública voltada para o âmbito educacional com o objetivo de sanar os desafios que envolvem o processo de ensino-aprendizagem, este estudo abordará o Projeto Criando Oportunidades– Reforço Escolar, meio pelo qual o Governo do Estado do Amazonas, por intermédio da Secretaria de Estado de Educação e Qualidade do Ensino/SEDUC, busca conduzir o aluno da Rede Pública Estadual com déficit de aprendizagem ao desenvolvimento de habilidades apontadas como críticas, através de um acompanhamento diferenciado, proporcionando em paralelo a prática docente aos acadêmicos licenciados das diversas áreas do conhecimento. O método de pesquisa bibliográfica e documental utilizado aponta que o reforço escolar se constitui de uma ferramenta poderosa, em que o professor se torna um “investigador” da problemática do aluno, ajudando-o na recuperação do seu desempenho e descoberta do seu potencial, buscando resgatar a sua autoestima e transformá-lo num estudante capaz de aprender. Portanto, o objetivo deste trabalho é mostrar o desenvolvimento de tal política e ação cuja lógica expressa a vontade de melhorar o cenário da educação do Estado nos diferentes níveis e modalidades, atendendo à demanda dos alunos com dificuldade no trato dos conteúdos

A type III effector protease NleC from enteropathogenic Escherichia coli targets NF-κB for degradation.

Published versio

An integrative multiomic network model links lipid metabolism to glucose regulation in coronary artery disease.

Elevated plasma cholesterol and type 2 diabetes (T2D) are associated with coronary artery disease (CAD). Individuals treated with cholesterol-lowering statins have increased T2D risk, while individuals with hypercholesterolemia have reduced T2D risk. We explore the relationship between lipid and glucose control by constructing network models from the STARNET study with sequencing data from seven cardiometabolic tissues obtained from CAD patients during coronary artery by-pass grafting surgery. By integrating gene expression, genotype, metabolomic, and clinical data, we identify a glucose and lipid determining (GLD) regulatory network showing inverse relationships with lipid and glucose traits. Master regulators of the GLD network also impact lipid and glucose levels in inverse directions. Experimental inhibition of one of the GLD network master regulators, lanosterol synthase (LSS), in mice confirms the inverse relationships to glucose and lipid levels as predicted by our model and provides mechanistic insights

Planning, implementing, and running a multicentre preterm birth study with biobank resources in Brazil : the preterm SAMBA study

Background. Our aim was to describe the steps in planning, implementing, and running a multicentre cohort study of maternal and perinatal health using a high-quality biobank comprised of maternal serum, plasma, and hair samples collected from five sites in Brazil.The Preterm SAMBA study, conducted by the Brazilian Network for Studies on Reproductive and Perinatal Health, was an innovative approach used to identify women at higher risk for preterm birth. It is also of great importance in the study of other maternal and perinatal complications in the context of Brazil, which is a middle-income country. Methods. We described phases of planning, implementing, and running the Preterm SAMBA study, a multicentre Brazilian cohort study of low-risk nulliparous pregnant women, to validate a set of metabolite biomarkers for preterm birth identified in an external cohort. Procedures and strategies used to plan, implement, and maintain this multicentre preterm birth study are described in detail. Barriers and experience cited in the current narrative are not usually discussed in the scientific literature or published study protocols. Results. Several barriers and strategies were identified in different phases of the Preterm SAMBA study at different levels of the study framework (steering committee; coordinating and local centres). Strategies implemented and resources used in the study are a legacy of the Brazilian Network, aimed at training collaborators in such complex settings. Conclusion. The Brazilian Network for Studies on Reproductive and Perinatal Health has gained some experience in conducting a multicentre cohort study using a resourceful biobank which may be helpful to other research groups and maternal/perinatal health networks that plan on employing a similar approach to a similar background

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

A GAMIFICAÇÃO COMO ESTRATÉGIA DE FORMAÇÃO DE PROFESSORES EM MATEMÁTICA: UMA ABORDAGEM BIBLIOGRÁFICA

Introduction: Teacher training in mathematics is crucial to improving the quality of mathematics teaching. In this context, gamification emerges as a promising strategy to promote the engagement and pedagogical effectiveness of educators. This study investigates the application of gamification in the training of mathematics teachers, aiming to understand its potential in the professional development of teachers. Objective: The research aims to critically analyze the application of gamification in the training of mathematics teachers, investigating its impact on the professional development and pedagogical practices of educators. Methods: The methodology adopted consists of a bibliographical research of a qualitative nature, which involves a critical review of the existing literature on gamification and teacher training in mathematics. Relevant studies, theories and concepts will be examined to support the analysis of the use of gamification in mathematics. Results and Discussion: The results and discussions highlight the importance of gamification as a promising strategy in the training of mathematics teachers, highlighting its potential benefits for the professional development of educators and for improving the teaching of the subject, as well as analyzing the practical implications and theories of gamification in mathematics teacher training. Final Considerations: Therefore, the study discussions suggest possible directions for future research. Therefore, the importance of continuing to investigate the use of gamification as an effective professional development strategy for mathematics teachers is highlighted, aiming to further improve the quality of teaching in this subject.Introducción: La formación docente en matemáticas es crucial para mejorar la calidad de la enseñanza de las matemáticas. En este contexto, la gamificación emerge como una estrategia prometedora para promover el compromiso y la eficacia pedagógica de los educadores. Este estudio investiga la aplicación de la gamificación en la formación de profesores de matemáticas, con el objetivo de comprender su potencial en el desarrollo profesional de los profesores. Objetivo: La investigación tiene como objetivo analizar críticamente la aplicación de la gamificación en la formación de profesores de matemáticas, investigando su impacto en el desarrollo profesional y las prácticas pedagógicas de los educadores. Métodos: La metodología adoptada consiste en una investigación bibliográfica de carácter cualitativo, que implica una revisión crítica de la literatura existente sobre gamificación y formación del profesorado de matemáticas. Se examinarán estudios, teorías y conceptos relevantes para respaldar el análisis del uso de la gamificación en matemáticas. Resultados y Discusión: Los resultados y discusiones resaltan la importancia de la gamificación como una estrategia prometedora en la formación de profesores de matemáticas, destacando sus potenciales beneficios para el desarrollo profesional de los educadores y para la mejora de la enseñanza de la materia, así como analizando las implicaciones prácticas. y teorías de la gamificación en la formación de profesores de matemáticas. Consideraciones finales: Por lo tanto, las discusiones del estudio sugieren posibles direcciones para futuras investigaciones. A formação de professores em matemática é crucial para aprimorar a qualidade do ensino matemático. Nesse contexto, a gamificação surge como uma estratégia promissora para promover o engajamento e a eficácia pedagógica dos educadores. Este estudo investiga a aplicação da gamificação na formação de professores de matemática, visando compreender seu potencial no desenvolvimento profissional dos docentes. Objetivo: A pesquisa objetiva analisar criticamente a aplicação da gamificação na formação de professores de matemática, investigando seu impacto no desenvolvimento profissional e nas práticas pedagógicas dos educadores.   Métodos: A metodologia adotada consiste em uma pesquisa bibliográfica de natureza qualitativa, que envolve a revisão crítica da literatura existente sobre gamificação e formação de professores em matemática. Serão examinados estudos, teorias e conceitos relevantes para fundamentar a análise do uso da gamificação na matemática. Resultados e Discussão: Os resultados e discussões destacam a importância da gamificação como uma estratégia promissora na formação de professores de matemática, evidenciando seus potenciais benefícios para o desenvolvimento profissional dos educadores e para a melhoria do ensino da disciplina, bem como analisar as implicações práticas e teóricas da gamificação na formação docente em matemática. Considerações Finais: Com isso, as discussões do estudo sugerem possíveis direções para pesquisas futuras. Portanto, destaca-se a importância de continuar investigando o uso da gamificação como uma estratégia eficaz de desenvolvimento profissional para professores de matemática, visando aprimorar ainda mais a qualidade do ensino nesta disciplina.Introdução: A formação de professores em matemática é crucial para aprimorar a qualidade do ensino matemático. Nesse contexto, a gamificação surge como uma estratégia promissora para promover o engajamento e a eficácia pedagógica dos educadores. Este estudo investiga a aplicação da gamificação na formação de professores de matemática, visando compreender seu potencial no desenvolvimento profissional dos docentes. Objetivo: A pesquisa objetiva analisar criticamente a aplicação da gamificação na formação de professores de matemática, investigando seu impacto no desenvolvimento profissional e nas práticas pedagógicas dos educadores.   Métodos: A metodologia adotada consiste em uma pesquisa bibliográfica de natureza qualitativa, que envolve a revisão crítica da literatura existente sobre gamificação e formação de professores em matemática. Serão examinados estudos, teorias e conceitos relevantes para fundamentar a análise do uso da gamificação na matemática. Resultados e Discussão: Os resultados e discussões destacam a importância da gamificação como uma estratégia promissora na formação de professores de matemática, evidenciando seus potenciais benefícios para o desenvolvimento profissional dos educadores e para a melhoria do ensino da disciplina, bem como analisar as implicações práticas e teóricas da gamificação na formação docente em matemática. Considerações Finais: Com isso, as discussões do estudo sugerem possíveis direções para pesquisas futuras. Portanto, destaca-se a importância de continuar investigando o uso da gamificação como uma estratégia eficaz de desenvolvimento profissional para professores de matemática, visando aprimorar ainda mais a qualidade do ensino nesta disciplina

Multifunctional, self-assembling, anionic peptide-lipid nanocomplexes for targeted siRNA delivery

Formulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated liposomes and cationic targeting peptides that overcome these problems. Biophysical measurements indicated that at optimal ratios of components, anionic PEGylated nanocomplexes formed spherical particles and that, unlike cationic nanocomplexes, were resistant to aggregation in the presence of serum, and achieved significant gene silencing although their non-PEGylated anionic counterparts were less efficient. We have evaluated the utility of anionic nanoparticles for the treatment of neuronal diseases by administration to rat brains of siRNA to BACE1, a key enzyme involved in the formation of amyloid plaques. Silencing of BACE1 was achieved in vivo following a single injection of anionic nanoparticles by convection enhanced delivery and specificity of RNA interference verified by 5' RACE-PCR and Western blot analysis of protein

Multilevel psychometric properties of the AHRQ hospital survey on patient safety culture

<p>Abstract</p> <p>Background</p> <p>The Agency for Healthcare Research and Quality (AHRQ) <it>Hospital Survey on Patient Safety Culture </it>was designed to assess staff views on patient safety culture in hospital settings. The purpose of this study was to examine the multilevel psychometric properties of the survey.</p> <p>Methods</p> <p>Survey data from 331 U.S. hospitals with 2,267 hospital units and 50,513 respondents were analyzed to examine the psychometric properties of the survey's items and composites. Item factor loadings, intraclass correlations (ICCs), design effects, internal consistency reliabilities, and multilevel confirmatory factor analyses (MCFA) were examined as well as intercorrelations among the survey's composites.</p> <p>Results</p> <p>Psychometric analyses confirmed the multilevel nature of the data at the individual, unit and hospital levels of analysis. Results provided overall evidence supporting the 12 dimensions and 42 items included in the AHRQ <it>Hospital Survey on Patient Safety Culture </it>as having acceptable psychometric properties at all levels of analysis, with a few exceptions. The Staffing composite fell slightly below cutoffs in a number of areas, but is conceptually important given its impact on patient safety. In addition, one hospital-level model fit indicator for the Supervisor/Manager Expectations & Actions Promoting Patient Safety composite was low (CFI = .82), but all other psychometrics for this scale were good. Average dimension intercorrelations were moderate at .42 at the individual level, .50 at the unit level, and .56 at the hospital level.</p> <p>Conclusions</p> <p>Psychometric analyses conducted on a very large database of hospitals provided overall support for the patient safety culture dimensions and items included in the AHRQ <it>Hospital Survey on Patient Safety Culture</it>. The survey's items and dimensions overall are psychometrically sound at the individual, unit, and hospital levels of analysis and can be used by researchers and hospitals interested in assessing patient safety culture. Further research is needed to study the criterion-related validity of the survey by analysing the relationship between patient safety culture and patient outcomes and studying how to improve patient safety culture.</p

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO