12,305 research outputs found

    Economia colaborativa

    Get PDF
    A importância de se proceder à análise dos principais desafios jurídicos que a economia colaborativa coloca – pelas implicações que as mudanças de paradigma dos modelos de negócios e dos sujeitos envolvidos suscitam − é indiscutível, correspondendo à necessidade de se fomentar a segurança jurídica destas práticas, potenciadoras de crescimento económico e bem-estar social. O Centro de Investigação em Justiça e Governação (JusGov) constituiu uma equipa multidisciplinar que, além de juristas, integra investigadores de outras áreas, como a economia e a gestão, dos vários grupos do JusGov – embora com especial participação dos investigadores que integram o grupo E-TEC (Estado, Empresa e Tecnologia) – e de outras prestigiadas instituições nacionais e internacionais, para desenvolver um projeto neste domínio, com o objetivo de identificar os problemas jurídicos que a economia colaborativa suscita e avaliar se já existem soluções para aqueles, refletindo igualmente sobre a conveniência de serem introduzidas alterações ou se será mesmo necessário criar nova regulamentação. O resultado desta investigação é apresentado nesta obra, com o que se pretende fomentar a continuação do debate sobre este tema.Esta obra é financiada por fundos nacionais através da FCT — Fundação para a Ciência e a Tecnologia, I.P., no âmbito do Financiamento UID/05749/202

    Impact of gut microbiota on expression of genes involved in hepatic and intestinal metabolism: Role for cardiometabolic disease

    Get PDF
    Einleitung - Eine Modulation kardiometabolischer Erkrankungen über das Darm-Mikrobiom rückt zunehmend in den Fokus aktueller kardiovaskulärer Forschung. Zahlreiche Studien belegen die Interaktion zwischen den Darmbakterien und bedeutsamen Stoffwechselwegen wie dem Cholesterin- sowie Glukose-Metabolismus, welche im dysregulierten Zustand wichtige atherosklerotische Risikofaktoren darstellen. Eine genaue Charakterisierung der Einflussnahme des Darm-Mikrobioms könnte zu neuen Therapiestrategien für kardiometabolische Erkrankungen führen. Ziel meiner Forschungsarbeit ist die Analyse der Partizipation des Darm-Mikrobioms am Cholesterin- Metabolismus in Abhängigkeit von der Nahrungszusammensetzung (Standarddiät vs. hochfettreiche Diät) sowie an der cholesterinsenkenden Wirkung einer Atorvastatin- Therapie. Zudem wurde ein möglicher langfristiger Einfluss des Darm-Mikrobiom abhängigen Metaboliten Propionat auf den GLP-1-Metabolismus untersucht. Methodik - Im tierexperimentellen Versuch wurden Mäuse (C57BL/6J) mit intaktem oder depletiertem Darm-Mikrobiom mit verschiedenen Spezialdiäten (Standarddiät vs. hochfettreiche Diät) sowie mit Atorvastatin behandelt. Ein mikrobieller Einfluss auf die Expression Cholesterin-regulierender Gene in hepatischen und intestinalen Organproben wurde mittels quantitativer Real-time-PCR untersucht. Ein langfristiger Einfluss einer oralen Supplementation mit Propionat auf die Expression von Genen des GLP-1-Metabolismus in Mäusen (C57BL/6J, ApoE-/-) sowie auf die GLP- 1-Plasmakonzentration in Menschen wurde mittels quantitativer Real-time-PCR bzw. Sandwich-ELISA untersucht. Resultate - In Abwesenheit des Darm-Mikrobioms zeigte sich unter der Standarddiät eine dysregulierte Expression von Genen des Gallensäure-Metabolismus sowie der hepatischen Cholesterin-Homöostase. Unter der hochfettreichen Diät konnte kein direkter mikrobieller Einfluss auf die Genexpression festgestellt werden. Die Atorvastatinvermittelte Regulation der Expression Cholesterin-regulierender Gene zeigte sich zum Teil abhängig von einem intakten Darm-Mikrobiom (1). Im Rahmen der oralen Supplementation mit Propionat konnte kein nachhaltig stimulierender Effekt auf die Expression intestinaler Gene des GLP-1-Metabolismus sowie auf die GLP-1-Plasmakonzentration beobachtet werden. Schlussfolgerung – Es konnte gezeigt werden, dass das Darm-Mikrobiom an der physiologischen Cholesterin-Homöostase unter einer Standarddiät beteiligt ist. Darüber hinaus konnte in dieser Arbeit erstmalig gezeigt werden, dass das Darm-Mikrobiom an der Atorvastatin vermittelten Regulation der Expression Cholesterin-regulierender Gene beteiligt ist und somit zum cholesterinsenkenden Effekt des Atorvastatins beiträgt (1). Weiterhin konnte gezeigt werden, dass mögliche protektive Effekte des Darm-Mikrobiom abhängigen Metaboliten Propionat auf den kardiometabolischen Stoffwechsel vermutlich nicht über eine langfristige Modulation des GLP-1-Metabolismus erzielt werden.Introduction - Growing evidence suggests a gut microbial involvement in metabolic pathways contributing to cardiometabolic diseases, such as dyslipidemia and impaired glucose tolerance or diabetes. Since dysregulations in the cholesterol- and glucose metabolism are major risk factors for cardiovascular disease, detailed knowledge about the metabolic interactions between host and gut microbiota could lead to new approaches for treatment of cardiometabolic diseases. The aim of this research was to investigate the diet-dependent (standarddiet vs. high fat diet) impact of the gut microbiota on cholesterolmetabolism as well as its impact on the cholesterol lowering effect of atorvastatin. Moreover, it was examined whether oral supplementation with the gut microbiota dependent metabolite propionate has a sustainable effect on GLP-1-metabolism. Methods – Mice (C57BL/6J) with either an intact or depleted gut microbiome were fed diets diverging in nutrient composition (standarddiet vs. high fat diet) and some of the mice additionally received atorvastatin. A microbial-dependent regulation of gene expression of cholesterol-regulating genes in hepatic and intestinal tissue was examined by quantitative real-time-PCR. The effect of oral supplementation of propionate on GLP-1 gene expression in mice (C57BL/6J, ApoE-/-) as well as on GLP-1 plasma concentration in humans was examined by quantitative real-time-PCR and Sandwich-ELISA respectively. Results - Mice with depleted gut microbiota displayed a dysregulated expression of genes involved in bile acid metabolism and hepatic cholesterol-homeostasis upon standarddiet. Upon high fat diet direct microbial influence on gene expression was lacking. However, atorvastatin mediated effects on the expression of cholesterol regulating genes were partly dependent on the gut microbiota (1). Oral supplementation of propionate had no persistent stimulating effect neither on intestinal gene expression in mice nor on plasma concentrations of GLP-1 in humans. Conclusion – The results of this study show that the gut microbiota is involved in the physiologic cholesterol-homeostasis upon a standarddiet. Furthermore, for the first time, this study shows that the gut microbiota participates in atorvastatin mediated regulation of cholesterol-regulating genes and therefore may contribute to the cholesterol lowering effect of atorvastatin (1). Additionally, the findings of this study suggest that the postulated protective effects of propionate on cardiometabolic pathways are likely not mediated by a sustainable stimulation of GLP-1-metabolism

    Examples of works to practice staccato technique in clarinet instrument

    Get PDF
    Klarnetin staccato tekniğini güçlendirme aşamaları eser çalışmalarıyla uygulanmıştır. Staccato geçişlerini hızlandıracak ritim ve nüans çalışmalarına yer verilmiştir. Çalışmanın en önemli amacı sadece staccato çalışması değil parmak-dilin eş zamanlı uyumunun hassasiyeti üzerinde de durulmasıdır. Staccato çalışmalarını daha verimli hale getirmek için eser çalışmasının içinde etüt çalışmasına da yer verilmiştir. Çalışmaların üzerinde titizlikle durulması staccato çalışmasının ilham verici etkisi ile müzikal kimliğe yeni bir boyut kazandırmıştır. Sekiz özgün eser çalışmasının her aşaması anlatılmıştır. Her aşamanın bir sonraki performans ve tekniği güçlendirmesi esas alınmıştır. Bu çalışmada staccato tekniğinin hangi alanlarda kullanıldığı, nasıl sonuçlar elde edildiği bilgisine yer verilmiştir. Notaların parmak ve dil uyumu ile nasıl şekilleneceği ve nasıl bir çalışma disiplini içinde gerçekleşeceği planlanmıştır. Kamış-nota-diyafram-parmak-dil-nüans ve disiplin kavramlarının staccato tekniğinde ayrılmaz bir bütün olduğu saptanmıştır. Araştırmada literatür taraması yapılarak staccato ile ilgili çalışmalar taranmıştır. Tarama sonucunda klarnet tekniğin de kullanılan staccato eser çalışmasının az olduğu tespit edilmiştir. Metot taramasında da etüt çalışmasının daha çok olduğu saptanmıştır. Böylelikle klarnetin staccato tekniğini hızlandırma ve güçlendirme çalışmaları sunulmuştur. Staccato etüt çalışmaları yapılırken, araya eser çalışmasının girmesi beyni rahatlattığı ve istekliliği daha arttırdığı gözlemlenmiştir. Staccato çalışmasını yaparken doğru bir kamış seçimi üzerinde de durulmuştur. Staccato tekniğini doğru çalışmak için doğru bir kamışın dil hızını arttırdığı saptanmıştır. Doğru bir kamış seçimi kamıştan rahat ses çıkmasına bağlıdır. Kamış, dil atma gücünü vermiyorsa daha doğru bir kamış seçiminin yapılması gerekliliği vurgulanmıştır. Staccato çalışmalarında baştan sona bir eseri yorumlamak zor olabilir. Bu açıdan çalışma, verilen müzikal nüanslara uymanın, dil atış performansını rahatlattığını ortaya koymuştur. Gelecek nesillere edinilen bilgi ve birikimlerin aktarılması ve geliştirici olması teşvik edilmiştir. Çıkacak eserlerin nasıl çözüleceği, staccato tekniğinin nasıl üstesinden gelinebileceği anlatılmıştır. Staccato tekniğinin daha kısa sürede çözüme kavuşturulması amaç edinilmiştir. Parmakların yerlerini öğrettiğimiz kadar belleğimize de çalışmaların kaydedilmesi önemlidir. Gösterilen azmin ve sabrın sonucu olarak ortaya çıkan yapıt başarıyı daha da yukarı seviyelere çıkaracaktır

    Anuário científico da Escola Superior de Tecnologia da Saúde de Lisboa - 2021

    Get PDF
    É com grande prazer que apresentamos a mais recente edição (a 11.ª) do Anuário Científico da Escola Superior de Tecnologia da Saúde de Lisboa. Como instituição de ensino superior, temos o compromisso de promover e incentivar a pesquisa científica em todas as áreas do conhecimento que contemplam a nossa missão. Esta publicação tem como objetivo divulgar toda a produção científica desenvolvida pelos Professores, Investigadores, Estudantes e Pessoal não Docente da ESTeSL durante 2021. Este Anuário é, assim, o reflexo do trabalho árduo e dedicado da nossa comunidade, que se empenhou na produção de conteúdo científico de elevada qualidade e partilhada com a Sociedade na forma de livros, capítulos de livros, artigos publicados em revistas nacionais e internacionais, resumos de comunicações orais e pósteres, bem como resultado dos trabalhos de 1º e 2º ciclo. Com isto, o conteúdo desta publicação abrange uma ampla variedade de tópicos, desde temas mais fundamentais até estudos de aplicação prática em contextos específicos de Saúde, refletindo desta forma a pluralidade e diversidade de áreas que definem, e tornam única, a ESTeSL. Acreditamos que a investigação e pesquisa científica é um eixo fundamental para o desenvolvimento da sociedade e é por isso que incentivamos os nossos estudantes a envolverem-se em atividades de pesquisa e prática baseada na evidência desde o início dos seus estudos na ESTeSL. Esta publicação é um exemplo do sucesso desses esforços, sendo a maior de sempre, o que faz com que estejamos muito orgulhosos em partilhar os resultados e descobertas dos nossos investigadores com a comunidade científica e o público em geral. Esperamos que este Anuário inspire e motive outros estudantes, profissionais de saúde, professores e outros colaboradores a continuarem a explorar novas ideias e contribuir para o avanço da ciência e da tecnologia no corpo de conhecimento próprio das áreas que compõe a ESTeSL. Agradecemos a todos os envolvidos na produção deste anuário e desejamos uma leitura inspiradora e agradável.info:eu-repo/semantics/publishedVersio

    Psychological Resilience in Children and Adolescents: The Power of Self-Recovery

    Get PDF
    Many children in the world grow up without good enough opportunities under challenging conditions such as poverty, violence, neglect, abuse, family discord and diseases. These conditions hinder the mental, emotional and social development of children and young people, making it difficult for them to reach their potential to become healthy adults. In addition to all these, there are children who can survive even in the most severe conditions and continue their development with health and functionality. Psychological resilience is a resource that protects and develops the psychological well-being of children and adolescents, rather than an invariable, innate feature, it is a dynamic process that can be developed, continuous and shaped by the interaction of the individual with his own internal factors and environmental factors. The aim of this study is to present a review of the literature on resilience research from past to present. The article includes the definition of resilience, the history of resilience research, components of resilience, models, measurement, interventions, and future directions in resilience research. Investments in the development of resilience in children and adolescents will produce health-promoting outcomes that balance individual and community-based psychological well-being throughout life, including positive outcomes and potential improvements

    Mechanism of Qihuang needle therapy in the management of tic disorders: a clinical trial protocol

    Get PDF
    BackgroundQihuang needle therapy is a newly developed acupuncture therapy to treat tic disorders in clinical practice. However, the mechanism to reduce tic severity remains unknown. Changes in intestinal flora and circulation metabolites are perhaps the potential pathogenesis of tic disorders. As a result, we present a protocol for a controlled clinical trial using multi-omics analysis to probe the mechanism of the Qihuang needle in managing tic disorders.MethodsThis is a matched-pairs design, controlled, clinical trial for patients with tic disorders. Participants will be allocated to either an experimental group or a healthy control group. The main acupoints are Baihui (GV20), Yintang (EX-HN3), and Jueyinshu (BL14). The experimental group will receive Qihuang needle therapy for a month, while the control group will receive no interventions.Expected outcomesThe change in the severity of the tic disorder is set as the main outcome. Secondary outcomes include gastrointestinal severity index and recurrence rate, which will be calculated after a 12-week follow-up. Gut microbiota, measured by 16S rRNA gene sequencing; serum metabolomics, assessed via LC/MS; and serum zonulin, assessed by enzyme-linked immunosorbent assay (ELISA), will be used as biological specimen analysis outcomes. The present study will investigate the possible interactions between intestinal flora and serum metabolites and the improvement of clinical profiles, which may elucidate the mechanism of Qihuang needle therapy for tic disorders.Trial registrationThis trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/). Registration number: ChiCTR2200057723, Date: 2022-04-14

    Machine Learning Research Trends in Africa: A 30 Years Overview with Bibliometric Analysis Review

    Full text link
    In this paper, a critical bibliometric analysis study is conducted, coupled with an extensive literature survey on recent developments and associated applications in machine learning research with a perspective on Africa. The presented bibliometric analysis study consists of 2761 machine learning-related documents, of which 98% were articles with at least 482 citations published in 903 journals during the past 30 years. Furthermore, the collated documents were retrieved from the Science Citation Index EXPANDED, comprising research publications from 54 African countries between 1993 and 2021. The bibliometric study shows the visualization of the current landscape and future trends in machine learning research and its application to facilitate future collaborative research and knowledge exchange among authors from different research institutions scattered across the African continent

    The Genetics of Pain: An exploration of gene-by-environment interactions and their effects on pain

    Get PDF
    The findings presented in this dissertation are part of the bigger SYMBIOME project which aims to use the biopsychosocial model of pain to develop a prognostic clinical phenotype for people that experience musculoskeletal (MSK) trauma. Chapter 2 presents an exploratory analysis to assess the relationships between genetic polymorphisms and pain severity and interference. Early childhood trauma was also explored as a moderator between genetic polymorphisms and pain outcomes. For pain severity, major allele carriers (A/A and G/A) of FKBP5 rs9394314 reported significantly higher scores than minor allele carriers (G/G). Further, major allele carriers who had at least one adverse childhood experience (ACE) reported significantly higher scores than minor allele carriers with at least one ACE. For pain interference, minor allele carriers (G/G) of CNR2 rs2501431 scored significantly higher than major allele carriers (A/A and G/A). Chapter 3 presents a cluster analysis that combines genotypes of FKBP5 rs9394314 and CNR2 rs2501431 to explore meaningful relationships with pain and trauma-related distress. ACE was also explored as a moderator of these relationships. Three clusters were identified where the second cluster characterized by major allele carriers of rs9394314 and minor allele carriers of rs2501431 reported significantly higher pain-related functional interference scores. Participants in the second cluster with at least one ACE reported higher pain interference and traumatic distress scores compared to the third cluster, while participants in the first cluster with at least one ACE reported higher pain severity compared to the first cluster. Chapter 4 presents genomic structural equation models (SEM) that explore the relationships of genotypes with trauma-related distress using the traumatic injuries distress scale (TIDS), ACE, and recovery outcomes. The results demonstrate a relationship between TIDS and recovery outcomes, and an indirect relationship between FKBP5 rs9394314 and recovery outcomes exist which is mediated by TIDS. Major allele carriers of FKBP5 rs9394314 reported higher TIDS scores, which was also demonstrated for participants that had at least one ACE. Major allele carriers that scored higher on the TIDS were predicted to be in the none-recovered category. These results support the notion that gene-x-environment interactions may play an important role in pain and recovery

    Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico

    Get PDF
    Valve replacement remains as the standard therapeutic option for aortic stenosis patients, aiming at abolishing pressure overload and triggering myocardial reverse remodeling. However, despite the instant hemodynamic benefit, not all patients show complete regression of myocardial hypertrophy, being at higher risk for adverse outcomes, such as heart failure. The current comprehension of the biological mechanisms underlying an incomplete reverse remodeling is far from complete. Furthermore, definitive prognostic tools and ancillary therapies to improve the outcome of the patients undergoing valve replacement are missing. To help abridge these gaps, a combined myocardial (phospho)proteomics and pericardial fluid proteomics approach was followed, taking advantage of human biopsies and pericardial fluid collected during surgery and whose origin anticipated a wealth of molecular information contained therein. From over 1800 and 750 proteins identified, respectively, in the myocardium and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated proteins were detected. Gene annotation and pathway enrichment analyses, together with discriminant analysis, are compatible with a scenario of increased pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by complement activity and other extrinsic factors, such as death receptor activators), acute-phase response, immune system activation and fibrosis. Specific validation of some targets through immunoblot techniques and correlation with clinical data pointed to complement C3 β chain, Muscle Ring Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation regulated kinase 1A (DYRK1A) as potential markers of an incomplete response. In addition, kinase prediction from phosphoproteome data suggests that the modulation of casein kinase 2, the family of IκB kinases, glycogen synthase kinase 3 and DYRK1A may help improve the outcome of patients undergoing valve replacement. Particularly, functional studies with DYRK1A+/- cardiomyocytes show that this kinase may be an important target to treat cardiac dysfunction, provided that mutant cells presented a different response to stretch and reduced ability to develop force (active tension). This study opens many avenues in post-aortic valve replacement reverse remodeling research. In the future, gain-of-function and/or loss-of-function studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic targets. Besides, clinical studies in larger cohorts will bring definitive proof of complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de referência para doentes com estenose aórtica e visa a eliminação da sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica. Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes apresentam regressão completa da hipertrofia do miocárdio, ficando com maior risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os mecanismos biológicos subjacentes a uma remodelagem reversa incompleta ainda não são claros. Além disso, não dispomos de ferramentas de prognóstico definitivos nem de terapias auxiliares para melhorar a condição dos pacientes indicados para substituição da válvula. Para ajudar a resolver estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica para a caracterização, respetivamente, do miocárdio e do líquido pericárdico foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em ambiente cirúrgico. Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90 proteínas desreguladas foram detetadas. As análises de anotação de genes, de enriquecimento de vias celulares e discriminativa corroboram um cenário de aumento da expressão de genes pro-hipertróficos e de síntese proteica, um sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular (potencialmente acelerada pela atividade do complemento e por outros fatores extrínsecos que ativam death receptors), com ativação da resposta de fase aguda e do sistema imune, assim como da fibrose. A validação de alguns alvos específicos através de immunoblot e correlação com dados clínicos apontou para a cadeia β do complemento C3, a Muscle Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma, sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição dos pacientes indicados para intervenção. Em particular, a avaliação funcional de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes responderam de forma diferente ao estiramento e mostraram uma menor capacidade para desenvolver força (tensão ativa). Este estudo levanta várias hipóteses na investigação da remodelagem reversa. No futuro, estudos de ganho e/ou perda de função realizados em cardiomiócitos isolados ou em modelos animais de banding-debanding da aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos encontrados. Além disso, estudos clínicos em coortes de maior dimensão trarão conclusões definitivas quanto ao valor de prognóstico do complemento C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin
    corecore