Association between bilirubin and lipid profile in Portuguese elderly individuals

Several studies showed that mildly elevated bilirubin blood concentration is inversely associated to coronary artery disease (CAD). The most commonly mechanism contributing to CAD prevention is the bilirubin antioxidant effect, protecting several macromolecules from oxidation. Recently, other studies have found that higher serum bilirubin levels (BL) are associated with beneficial effects improving lipid profile and that might contribute to decrease cholesterol and triacylglycerol. In the meantime, a consistently negative association between BL and body mass index (BMI) was observed. The aim of this study was evaluate the cardiovascular risk protection by bilirubin analyzing the association between bilirubin levels and lipid profile in elderly. Clinical data, anthropometric measurements (BMI, Visceral Fat and Body Fat Percentage), lipid profile (total cholesterol-TC; triglycerides-TG; high-density lipoprotein cholesterol-HDL-c; low-density lipoprotein cholesterol-LDL-c; apoliprotein A-Apo-A; apoliprotein B-Apo-B) were evaluated in 70 institutionalized elderly, 43 females (mean age= 88.2±5.5 years old) and 27 males (mean age= 87.7±7.7 years old). Anthropometric measurements were obtained by bioimpedance, using specific scale (Tanita BC Model: 545). The lipid parameters were performed in autoanalyzer (Cobas Mira S, Roche, Switzerland) using available commercial kits. Correlation analysis revealed positive associations between BL and the HDL-c in males (total bilirubin: r=0.51; p<0.007) and no association in females (r=0.40; p<0.50). Positive associations were also found to TB levels and Apo-A (males: r=0.40; p<0.50 and females: r=0.270; p<0.013). Interestingly, the conjugated bilirubin present a stronger positive association with this two parameters (male: r=0.64; p<0.000; female: r=0.29; p<0.052). No associations were found between bilirubin and triglycerides; total cholesterol and anthropometric measurements. Low levels of HDL-c are a risk factor for coronary heart disease. A similar association has been shown for Apo-A1. These results suggest higher bilirubin is associated with higher cardioprotective agents, which indicates that the determination of total bilirubin should be included for more accurate cardiovascular disease risk assessment.info:eu-repo/semantics/publishedVersio

A Combined Approach Exploring Gene Function Based on Worm-Human Orthology

Background: Many aspects of the nematode Caenorhabditis elegans biology are conservedbetween invertebrates and vertebrates establishing this particular organism as an excellent geneticmodel. Because of its small size, large populations and self-fertilization of the hermaphrodite,functional predictions carried out by genetic modifications as well as RNAi screens, can be rapidlytested.Results: In order to explore the function of a set of C. elegans genes of unknown function, as wellas their potential functional roles in the human genome, we performed a phylogenetic analysis toselect the most probable worm orthologs. A total of 13 C. elegans genes were subjected to downregulationvia RNAi and characterization of expression profiles using GFP strains. Previouslyunknown distinct expression patterns were observed for four of the analyzed genes, as well as fourvisible RNAi phenotypes. In addition, subcellular protein over-expression profiles of the humanorthologs for seven out of the thirteen genes using human cells were also analyzed.Conclusion: By combining a whole-organism approach using C. elegans with complementaryexperimental work done on human cell lines, this analysis extends currently available informationon the selected set of genes

Desenvolvimento de recursos humanos: um recorte contemporâneo

A aprendizagem e o desenvolvimento contínuo são fatores nucleares no paradigma contemporâneo das organizações, das sociedades e dos indivíduos. É neste contexto que o Desenvolvimento de Recursos Humanos (DRH) emerge como uma área, profissional e científica, progressivamente mais forte e autónoma no campo dos Recursos Humanos. É face a este enquadramento, que procuramos nesta dissertação compreender a conceptualização contemporânea do DRH, explorando as principais abordagens, dimensões e problemáticas associadas. É com este intuito que realizamos 3 estudos. O primeiro consiste numa revisão sistemática da literatura no sentido de conhecer a construção conceptual cientifica sobre o DRH. No segundo estudo, analisamos as associações profissionais de DRH com o intuito de adquirir uma perspetiva mais profissionalizante da realidade do DRH a nível internacional. O terceiro estudo consiste num inquérito por questionário a profissionais de DRH com a finalidade de conhecer a realidade profissional de DRH em Portugal. A investigação revelou que o DRH é um processo diretamente ligado ao potencial humano disponível numa determinada sociedade ou organização, que visa contribuir para que as pessoas adquiram e melhorem continuamente as competências necessárias para desempenhar as suas funções ocupacionais e, consequentemente, que as sociedades e as organizações tirem maior proveito do seu capital humano. Por este motivo, revela-se fundamental que as organizações (laborais e sociais) desenvolvam estratégias de DRH para que possam gerir a sua força de trabalho de forma organizada e alinhada com as suas missões e objetivos. Das dimensões mais associadas ao DRH destaca-se o contexto económico-social (reportando-se às questões da qualificação e do mercado de trabalho), o contexto organizacional (associado às diversas atividades de aprendizagem e melhoria contínua) e o desenvolvimento individual (relacionado com a gestão de carreira dos indivíduos). Em todas as abordagens emerge como processo de reforço da capacidade interna das sociedades e das organizações para lidar com os desafios atuais e futuros.Continuous learning and development are central factors on the contemporary paradigm of organizations, societies and individuals. It is in this context that Human Resource Development (HRD) emerges as a professional and scientific field progressively stronger and more autonomous among the Human Resources domain. It is facing this framework that, with this paper, we aim to understand the contemporary conceptualization of HRD, exploring its main approaches, dimensions and associated issues. It is with this goal that we developed three different studies. The first study consisting on a systematic revision of literature, aiming to understand the conceptual scientific construction on HRD. A second study, which analyzes HRD professional associations with the intent of acquiring a more professionalizing perspective of the reality of HRD worldwide. The third study consists on a questionnaire to HRD professionals with the purpose of approaching the professional reality of HRD in Portugal. The research revealed that HRD is a process directly connected to the human potential available in a determined society or organization. It aims to contribute to the acquisition and continuously improvement of individuals occupational skills and, consequently, to societies and organizations, enabling them to take a better benefit from their human capital. For this motive, the development of HRD strategies point out to be fundamental towards the alignment of society, organizations, and people, as the primer labor force element. The most highlighted dimensions associated with HRD, are the socio-economic context (reporting to the questions of qualification and labor market), the organizational context (associated to the several activities of learning and continuous improvement) and the individual development (related to the management of one´s individual career). In all the approaches, HRD emerges as a reinforcement process of the intern skills of societies and organizations in order to deal with current and future challenges.info:eu-repo/semantics/publishedVersio

Functional Characterization in Caenorhabditis Elegans of Transmembrane Worm-Human Orthologs

Background: The complete genome sequences for human and the nematode Caenorhabditiselegans offer an opportunity to learn more about human gene function through functionalcharacterization of orthologs in the worm. Based on a previous genome-wide analysis of wormhumanorthologous transmembrane proteins, we selected seventeen genes to exploreexperimentally in C. elegans. These genes were selected on the basis that they all have highconfidence candidate human orthologs and that their function is unknown. We first analyzed theirphylogeny, membrane topology and domain organization. Then gene functions were studiedexperimentally in the worm by using RNA interference and transcriptional gfp reporter genefusions.Results: The experiments gave functional insights for twelve of the genes studied. For example,C36B1.12, the worm ortholog of three presenilin-like genes, was almost exclusively expressed inhead neurons, suggesting an ancient conserved role important to neuronal function. We proposea new transmembrane topology for the presenilin-like protein family. sft-4, the worm ortholog ofsurfeit locus gene Surf-4, proved to be an essential gene required for development during the larvalstages of the worm. R155.1, whose human ortholog is entirely uncharacterized, was implicated inbody size control and other developmental processes.Conclusions: By combining bioinformatics and C. elegans experiments on orthologs, we providefunctional insights on twelve previously uncharacterized human genes

Effect of sonic agitation of a binary mixture of solvents on filling remnants removal as an alternative to apical enlargement — a micro-CT study

Background: This work aimed to evaluate the efficacy of sonic agitation of a binary mixture of solvents (methyl ethyl ketone/tetrachloroethylene) on filling remnants removal and compare the effects of solvent agitation with the enlargement to the next instrument size. Methods: Twenty-four mandibular incisors were prepared with ProTaper Next (X1, X2) and obturated with the single-cone technique and AH Plus sealer. The teeth were retreated with ProTaper Universal Retreatment and ProTaper Next and divided into two groups (n = 12) according to the final instrument (X3 or X4). All canals were submitted to a supplementary procedure consisting of a mixture of solvents―methyl ethyl ketone/tetrachloroethylene, agitated with EndoActivator. The volume of filling remnants was assessed through micro-computed tomography in the apical 5 mm. Statistical analysis was performed with a significance level of 5%. Results: The supplementary procedure of agitation of the solvent mixture was beneficial in both groups (p p > 0.05). Conclusions: An additional step with a two-solvent solution potentiated by EndoActivator showed to be very effective for the removal of gutta-percha and resinous sealer remnants from apical root canals of mandibular incisors, avoiding further enlargement.This article was supported by National Funds through FCT-Fundacao para a Ciencia e a Tecnologia, I.P., within CINTESIS, R&D Unit (reference UIDB/4255/2020)

O enoturismo em Portugal : da "cultura" do vinho ao vinho como cultura : a oferta enoturística nacional e as suas implicações no desenvolvimento local e regional

Tese de doutoramento, Geografia (Planeamento Regional e Urbano), 2009, Universidade de Lisboa, Faculdade de LetrasO Enoturismo é um fenómeno característico de Modernidade, com uma dupla valência e significado: constitui-se como uma actividade turística complementar à oferta turística nacional, predominantemente balnear. Encerra produtos turísticos onde o interesse pelo conhecimento do vinho e da vinha nas suas dimensões material, cultural e gastronómica, ou seja, simbólica, se materializam. Pode revelar-se uma actividade complementar da actividade rural e agrícola vitivinícola, ou motor de outras actividades tradicionais, seguindo uma lógica de pluriactividade (Covas; Cavaco) essencial aos agentes que em meio rural equacionam a sustentabilidade dos seus negócios. Mundialmente esta bivalência é reconhecida. Os casos de benchmarking que retratam os principais países europeus onde a actividade se desenvolve: França, Itália e Espanha confirmam este cenário. No Novo Mundo , ainda que repleto de especificidades e diferenças quando comparado com as realidades e escala europeia, possui o mesmo sentido de dupla valência. Em Portugal, esta actividade encontra-se ainda na sua primeira idade. Assume-se que a passagem do rural a produto turístico implica a eleição de alguns traços de ruralidade que se transformam em bandeiras do Destino Enoturístico , numa lógica de (re)constitução social desta realidade. Este fenómeno é visível quando se analisa a imprensa especializada, em boa parte responsável por este processo de transformação/criação da imagem do rural, inscrevendo-se um Novo rural. A valorização do passado, das tradições e do familiar são bivalentes: para os visitantes significam os argumentos que tornam o destino atractivo; para os agentes locais tornam-se num contributo que lhes permite a valorização e confirmação identitária há muito aspirada. No conjunto interferem na forma de organização e valorização do espaço: o agrícola, tornado rural, transforma-se agora em turístico, numa valorização endógena e exógena destes espaços e dos seus actores. A opção de análise à escala regional permite melhor retratar as suas especificidades, tendo-se optado pelas regiões do Minho, Douro, Alentejo e Setúbal. Considera-se que o Enoturismo é de particular relevância para estas regiões, não tanto pelos postos de trabalho que implica ou pelos lucros gerados, mas pelos processos de interiorização do prestígio e do valor que o trabalho da arte de fabricar o vinho induz. Esta imagem de um rural interessante para quem visita e prestigiante para quem nele participa podem constituir uma vantagem para o universo agrícola, como alavanca de algumas dinâmicas locais necessárias à sua perpetuação e fixação de populações neste meio. A proposta que é feita é, em certa medida, a comercialização do espaço rural, das suas paisagens, produtos, culturas, agentes, ou seja, do passado e do presente, de forma a garantir-lhes um futuro.Wine tourism is a modernity phenomenon, with a double valence and significance: it is a complement to the national tourism offer, predominantly based on coast and beach tourism. It includes tourism products where the knowledge of the wine and vineyards in their physical, cultural, gastronomic and symbolic dimensions. It may prove to be a complementary activity of wine agriculture and rural life, or a propulsion motor to other traditional activities, following a logic of "multiple-activities" (Covas; Cavaco) vital to sustainability of agents and their business in rural areas. Worldwide this double-valence is recognized. The benchmarking studies we made prove well similarities in the main European countries where the business is developing: France, Italy and Spain, reinforcing this scenario. In the "New World" it is possible to notice the same bivalent sense, though full of peculiarities and differences when compared with the realities and European scale. In Portugal, this activity is still in its infancy. It is assumed that the passage of the rural to the tourism product involves the election of some traces of countryside that are transformed into banners of "Wine Tourism Destination," a logic of social (re) constitution of this reality. This phenomenon is visible when looking at the specialized press, in large part responsible for this process of transformation / creation of the image of the countryside, signing up a "new" rural. The recovery of the value of the past, of traditions and of the family is their multiple meanings: for visitors it gives the arguments that make the destination attractive; for local agents it becomes in the contribute that allows them to recover the value and long-aspirated identity confirmation. Overall, they interfere in the way of organization and exploitation of space: the agricultural turned rural, now becomes touristic, an endogenous and exogenous value recovery of these spaces and its stakeholders. The option of a regional scale analysis allows for a better portray of their specificities, so the following regions were selected; Minho, Douro, Alentejo and Setubal. It is estimated that the wine tourism is of particular relevance to these regions, not so much by jobs that it involves or the profits generated, but for the process of internalization of the prestige and value that the work of "the art of making wine" leads. This image of a interesting rural region for those who visit and prestigious for those who participates in it, can be an advantage for the agricultural field, as a lever of some local dynamics required for its establishment and perpetuation of people in this environment. The proposal that is made is to some extent, the "commercialization" of rural land, its landscapes, products, cultures, agents, i.e., past and present, to ensure them a future.Fundação para a Ciência e Tecnologia (SFRH/BD/18033/2004 Compreender o Enoturismo em Portugal). Programa Operacional Ciência e Inovação 201

Recovery of depleted miR-146a in ALS cortical astrocytes reverts cell aberrancies and prevents paracrine pathogenicity on microglia and motor neurons

Copyright © 2021 Barbosa, Gomes, Sequeira, Gonçalves-Ribeiro, Pina, Carvalho, Moreira, Vaz, Vaz and Brites. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).Reactive astrocytes in Amyotrophic Lateral Sclerosis (ALS) change their molecular expression pattern and release toxic factors that contribute to neurodegeneration and microglial activation. We and others identified a dysregulated inflammatory miRNA profile in ALS patients and in mice models suggesting that they represent potential targets for therapeutic intervention. Such cellular miRNAs are known to be released into the secretome and to be carried by small extracellular vesicles (sEVs), which may be harmful to recipient cells. Thus, ALS astrocyte secretome may disrupt cell homeostasis and impact on ALS pathogenesis. Previously, we identified a specific aberrant signature in the cortical brain of symptomatic SOD1-G93A (mSOD1) mice, as well as in astrocytes isolated from the same region of 7-day-old mSOD1 mice, with upregulated S100B/HMGB1/Cx43/vimentin and downregulated GFAP. The presence of downregulated miR-146a on both cases suggests that it can be a promising target for modulation in ALS. Here, we upregulated miR-146a with pre-miR-146a, and tested glycoursodeoxycholic acid (GUDCA) and dipeptidyl vinyl sulfone (VS) for their immunoregulatory properties. VS was more effective in restoring astrocytic miR-146a, GFAP, S100B, HMGB1, Cx43, and vimentin levels than GUDCA, which only recovered Cx43 and vimentin mRNA. The miR-146a inhibitor generated typical ALS aberrancies in wild type astrocytes that were abolished by VS. Similarly, pre-miR-146a transfection into the mSOD1 astrocytes abrogated aberrant markers and intracellular Ca2+ overload. Such treatment counteracted miR-146a depletion in sEVs and led to secretome-mediated miR-146a enhancement in NSC-34-motor neurons (MNs) and N9-microglia. Secretome from mSOD1 astrocytes increased early/late apoptosis and FGFR3 mRNA in MNs and microglia, but not when derived from pre-miR-146a or VS-treated cells. These last strategies prevented the impairment of axonal transport and synaptic dynamics by the pathological secretome, while also averted microglia activation through either secretome, or their isolated sEVs. Proteomic analysis of the target cells indicated that pre-miR-146a regulates mitochondria and inflammation via paracrine signaling. We demonstrate that replenishment of miR-146a in mSOD1 cortical astrocytes with pre-miR-146a or by VS abrogates their phenotypic aberrancies and paracrine deleterious consequences to MNs and microglia. These results propose miR-146a as a new causal and emerging therapeutic target for astrocyte pathogenic processes in ALS.This work was supported by the Research Grant of the Santa Casa Scientific Research Program on ALS, by Santa Casa da Misericórdia de Lisboa (SCML), Portugal, Project Ref. ELA-2015-002 (to DB). Fundação para a Ciência e a Tecnologia (FCT) also supported the project PTDC/MED-NEU/31395/2017 (to DB), PTDC/MED-QUI/30021/2017 (to RM) and iMed. ULisboa (UIDB/04138/2020 and UIDP/04138/2020), together with Programa Operacional Regional de Lisboa and the Programa Operacional Competitividade e Internacionalização (LISBOA-01-0145-FEDER-031395 to DB). Individual fellowships MB (SFRH/BD/129586/2017), CG (SFRH/BD/102718/2014), AV (SFRH/BPD/76590/2011), and JG-R PD/BD/150342/2019 were from FCT. CS was a research fellowship recipient from SCML.info:eu-repo/semantics/publishedVersio