53 research outputs found

    Gender Differences in the Context of Obstructive Sleep Apnea and Metabolic Diseases

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    Funding: The author FM is funded by the Portuguese Foundation for Science and Technology with contract reference CEECIND/04266/2017.The relationship between obstructive sleep apnea (OSA) and endocrine and metabolic disease is unequivocal. OSA, which is characterized by intermittent hypoxia and sleep fragmentation, leads to and exacerbates obesity, metabolic syndrome, and type 2 diabetes (T2D) as well as endocrine disturbances, such as hypothyroidism and Cushing syndrome, among others. However, this relationship is bidirectional with endocrine and metabolic diseases being considered major risk factors for the development of OSA. For example, polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women of reproductive age, is significantly associated with OSA in adult patients. Several factors have been postulated to contribute to or be critical in the genesis of dysmetabolic states in OSA including the increase in sympathetic activation, the deregulation of the hypothalamus-pituitary axis, the generation of reactive oxygen species (ROS), insulin resistance, alteration in adipokines levels, and inflammation of the adipose tissue. However, probably the alterations in the hypothalamus-pituitary axis and the altered secretion of hormones from the peripheral endocrine glands could play a major role in the gender differences in the link between OSA-dysmetabolism. In fact, normal sleep is also different between men and women due to the physiologic differences between genders, with sex hormones such as progesterone, androgens, and estrogens, being also connected with breathing pathologies. Moreover, it is very well known that OSA is more prevalent among men than women, however the prevalence in women increases after menopause. At the same time, the step-rise in obesity and its comorbidities goes along with mounting evidence of clinically important sex and gender differences. Metabolic and cardiovascular diseases, seen as a men's illness for decades, presently are more common in women than in men and obesity has a higher association with insulin-resistance-related risk factors in women than in men. In this way, in the present manuscript, we will review the major findings on the overall mechanisms that connect OSA and dysmetabolism giving special attention to the specific regulation of this relationship in each gender. We will also detail the gender-specific effects of hormone replacement therapies on metabolic control and sleep apnea.publishersversionpublishe

    Gestão de projetos de obras de engenharia, na fase de concurso do processo de contratação pública

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    A gestão das empreitadas de obras públicas, consideradas na presente dissertação como projetos, têm um grande impacto em termos de duração do projeto, logo na fase de concurso. O presente estudo tem por objetivo servir de suporte à decisão para a redução dos tempos de execução das atividades do processo de concurso público, e para o planeamento de futuros processos. Cumulativamente, tem por objetivo fomentar uma cultura de gestão do projeto dentro da organização. Para o efeito, foi selecionada uma amostra de 15 processos de concurso público relativa a empreitadas de construção e reabilitação de infraestruturas de abastecimento de água e de saneamento de águas residuais, localizadas nas áreas de intervenção da AdVT, SA (Polos das Beiras e Alentejo), totalizando um montante de investimento de cerca de 16 milhões de euros e levados a cabo por diferentes gestores de projeto (gestores de procedimento - GP) pertencentes ao Departamento de Engenharia da organização. Foi aplicado o método Program Evaluation and Review Technique (PERT) para avaliar o tempo de conclusão do projeto e identificação do caminho crítico no processo de contratação pública da amostra selecionada. Como se poderia depreender, obedecendo o projeto a regras de contratação pública, as atividades são sequenciais não havendo atividades paralelas, neste sentido constatou-se que todas as atividades do processo estão no caminho critico.The management of public works contracts, considered in the present dissertation as projects, have a great impact in terms of project duration, in the tender phase. The purpose of this study is to support the decision to reduce the execution times of the public tender process and to plan future processes. Cumulatively, it aims to foster a culture of project management within the organization For this purpose, a sample of 15 public tender procedures related to construction and rehabilitation of water supply and wastewater sanitation infrastructure were selected, located in the intervention areas of AdVT, SA (Poles of Beiras and Alentejo), totaling an amount of investment of around 16 million euros and carried out by different project managers (procedure managers GP) belonging to the Engineering Department of the organization. The Program Evaluation and Review Technique (PERT) method was applied to evaluate the completion time of the project and identify the critical path in the public procurement process of the selected sample. As one could deduce by obeying the project to public contracting rules, the activities are sequential with no parallel activities, in this sense it was found that all activities of the process are in the critical path

    Trick or Treat?

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    Funding Information: Funding: AC and FOM were supported by grants and contracts from the Portuguese Foundation for Science and Technology, PD/BD/136863/2018 and CEECIND/04266/2017, respectively.Accumulating evidence suggests the existence of a strong link between metabolic syndrome and neurodegeneration. Indeed, epidemiologic studies have described solid associations between metabolic syndrome and neurodegeneration, whereas animal models contributed for the clarification of the mechanistic underlying the complex relationships between these conditions, having the development of an insulin resistance state a pivotal role in this relationship. Herein, we review in a concise manner the association between metabolic syndrome and neurodegeneration. We start by providing concepts regarding the role of insulin and insulin signaling pathways as well as the pathophysiological mechanisms that are in the genesis of metabolic diseases. Then, we focus on the role of insulin in the brain, with special attention to its function in the regulation of brain glucose metabolism, feeding, and cognition. Moreover, we extensively report on the association between neurodegeneration and metabolic diseases, with a particular emphasis on the evidence observed in animal models of dysmetabolism induced by hypercaloric diets. We also debate on strategies to prevent and/or delay neurodegeneration through the normalization of whole-body glucose homeostasis, particularly via the modulation of the carotid bodies, organs known to be key in connecting the periphery with the brain.publishersversionpublishe

    EDUCAÇÃO PROFISSIONAL NO PNE 2014-2024: TENDÊNCIAS E DESAFIOS

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    Versa sobre a abordagem da modalidade Educação Profissional no PNE 2014-2024. Identifica-se que a expansão da Rede Federal de Educação Profissional e Tecnológica, a institucionalização dos Institutos Federais e a integração das ações da educação profissional técnica de nível médio, da educação de jovens e adultos e da educação profissional e tecnológica são movimentos da política nacional brasileira para essa modalidade de ensino que vem se consolidando na última década. A partir desse pressuposto são discutidos alguns, dos muitos, desafios que emergem para a Educação Profissional na contemporaneidade

    Synthesis of polyurethanes with low volatile organic Compounds content for upholstery and automotive Articles

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    The manufacture of upholstery and automotive articles is linked to the release of Volatile Organic Compounds (hereinafter VOCs) during their manufacture, which have short and long-term effects on the health of users and the environment. In the leather sector, around 40 kg of VOCs are generated per 1000 kg of raw skin. This research work has focused on the synthesis of new and more sustainable urethane-based polymers that, in turn, allow the quality requirements of the finish to be met, which vary depending on the leather article manufactured. The main objective of the study is to minimize the content of VOCs in the different aliphatic polyurethanes synthesized in a pilot-scale reactor, making small modifications to the synthesis formulations. The synthesis route developed is based on the preparation of polymers of ionomeric polyurethanes and their subsequent dispersion in water. In the synthesis processes developed, the content of coalescing solvents and neutralizing agents, which directly contribute to the concentration of VOCs of the urethane polymers, is eliminated and / or minimized as much as possible. The new urethane-based polymers obtained have been analyzed according to the parameters of pH, viscosity, density and percentage of solids in the resin. Likewise, organoleptic tests (color, transparency, hardness, touch and tacking) and physical tests (tensile strength, water absorption, hardness and color change at 100°C for 24 hours) have been carried out on the film corresponding to each synthesized polyurethane resin. These products will be introduced in finishing formulations designed to obtain high-performance upholstery and automotive leather with minimal impact in terms of VOC content at the pilot level. Tests of fastness and physical resistance have been carried out to evaluate the performance of these leathers.This research work has been developed within the framework of the NoVOCs project (RTC-2016-4575-5) within the Collaboration Challenges program (2016-2018) approved by the Ministry of Economy and Competitiveness of Spain

    Dysmetabolism and Sleep Fragmentation in Obstructive Sleep Apnea Patients Run Independently of High Caffeine Consumption

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    Funding Information: This research was funded by the Portuguese Science and Technology Foundation (FCT) with the grant number CEECIND/04266/2017. Acknowledgments: The authors would like to thank Eunice Silva for technical support. Funding Information: Funding: This research was funded by the Portuguese Science and Technology Foundation (FCT) with the grant number CEECIND/04266/2017.Daytime hypersomnolence, the prime feature of obstructive sleep apnea (OSA), frequently leads to high coffee consumption. Nevertheless, some clinicians ask for patients’ caffeine avoidance. Caffeinated drinks are sometimes associated with more severe OSA. However, these effects are not consensual. Here we investigated the effect of caffeine consumption on sleep architecture and apnea/hypopnea index in OSA. Also, the impact of caffeine on variables related with dysmetabolism, dyslipidemia, and sympathetic nervous system (SNS) dysfunction were investigated. A total of 65 patients diagnosed with OSA and 32 without OSA were included after given written informed consent. Polysomnographic studies were performed. Blood was collected to quantify caffeine and its metabolites in plasma and biochemical parameters. 24 h urine samples were collected for catecholamines measurement. Statistical analyses were performed by SPSS: (1) non-parametric Mann-Whitney test to compare variables between controls and OSA; (2) multivariate logistic regression testing the effect of caffeine on sets of variables in the 2 groups; and (3) Spearmans’ correlation between caffeine levels and comorbidities in patients with OSA. As expected OSA development is associated with dyslipidemia, dysmetabolism, SNS dysfunction, and sleep fragmentation. There was also a significant increase in plasma caffeine levels in the OSA group. However, the higher consumption of caffeine by OSA patients do not alter any of these associations. These results showed that there is no apparent rationale for caffeine avoidance in chronic consumers with OSA.publishersversionpublishe

    Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice

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    © 2016. Published by The Company of Biologists Ltd.The neuroprotective role of carbon monoxide (CO) has been studied in a cell-autonomous mode. Herein, a new concept is disclosed - CO affects astrocyte-neuron communication in a paracrine manner to promote neuroprotection. Neuronal survival was assessed when co-cultured with astrocytes that had been pre-treated or not with CO. The CO-pre-treated astrocytes reduced neuronal cell death, and the cellular mechanisms were investigated, focusing on purinergic signaling. CO modulates astrocytic metabolism and extracellular ATP content in the co-culture medium. Moreover, several antagonists of P1 adenosine and P2 ATP receptors partially reverted CO-induced neuroprotection through astrocytes. Likewise, knocking down expression of the neuronal P1 adenosine receptor A2A-R (encoded by Adora2a) reverted the neuroprotective effects of CO-exposed astrocytes. The neuroprotection of CO-treated astrocytes also decreased following prevention of ATP or adenosine release from astrocytic cells and inhibition of extracellular ATP metabolism into adenosine. Finally, the neuronal downstream event involves TrkB (also known as NTRK2) receptors and BDNF. Pharmacological and genetic inhibition of TrkB receptors reverts neuroprotection triggered by CO-treated astrocytes. Furthermore, the neuronal ratio of BDNF to pro-BDNF increased in the presence of CO-treated astrocytes and decreased whenever A2A-R expression was silenced. In summary, CO prevents neuronal cell death in a paracrine manner by targeting astrocytic metabolism through purinergic signaling.publishersversionpublishe

    A Metabolic Signature to Monitor Endothelial Cell Differentiation, Activation, and Vascular Organization

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    Funding: The institutions are funded by Fundação para a Ciência e Tecnologia, Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), MOSTMICRO-ITQB (UIDB/04612/2020 and UIDP/04612/2020), and the Associated Laboratory LS4FUTURE (LA/P/0087/2020). Filipa Lopes-Coelho’s fellowship was funded by FCT (PD/BD/128337/2017). Luis G. Gonçalves was financed by an FCT contract according to DL57/2016 (SFRH/BPD/111100/2015). This work benefited from access to CERMAX, ITQB NOVA, Oeiras, Portugal, with equipment funded by FCT, project AAC 01/SAICT/2016.The formation of new blood vessels is an important step in the morphogenesis and organization of tissues and organs; hence, the success of regenerative medicine procedures is highly dependent on angiogenesis control. Despite the biotechnological advances, tissue engineering is still a challenge. Regarding vascular network formation, the regulators are well known, yet the identification of markers is pivotal in order to improve the monitoring of the differentiation and proliferation of endothelial cells, as well as the establishment of a vascular network supporting tissue viability for an efficacious implantation. The metabolic profile accompanies the physiological stages of cells involved in angiogenesis, being a fruitful hub of biomarkers, whose levels can be easily retrieved. Through NMR spectroscopy, we identified branched amino acids, acetate, and formate as central biomarkers of monocyte-to-endothelial-cell differentiation and endothelial cell proliferation. This study reinforces the successful differentiation process of monocytes into endothelial cells, allowing self-to-self transplantation of patient-derived vascular networks, which is an important step in tissue engineering, since monocytes are easily isolated and autologous transplantation reduces the immune rejection events.publishersversionpublishe

    Circulating Dopamine Is Regulated by Dietary Glucose and Controls Glucagon-like 1 Peptide Action in White Adipose Tissue

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    Funding: This work was supported by a grant from GIFT (Grupo de Investigação Fundamental e Translational) from the Portugal Society of Diabetes and Portugal Foundation for Science and Technology (PEst UID/NEU/04539/2013 and UID/NEU/04539/2019: CNC.IBILI; PEst UIDB/04539/2020 and UIDP/04539/2020: CIBB). G.T. and D.R.S. were supported by Ph.D. Grants from the Portuguese Foundation for Science and Technology (PD/BD/127822/2016 and 2021.08160.BD respectively). J.F.S. is supported by a contract from the Portuguese Foundation for Science and Technology (CEEC IND/02428/2018).Dopamine directly acts in the liver and white adipose tissue (WAT) to regulate insulin signaling, glucose uptake, and catabolic activity. Given that dopamine is secreted by the gut and regulates insulin secretion in the pancreas, we aimed to determine its regulation by nutritional cues and its role in regulating glucagon-like peptide 1 (GLP-1) action in WAT. Solutions with different nutrients were administered to Wistar rats and postprandial dopamine levels showed elevations following a mixed meal and glucose intake. In high-fat diet-fed diabetic Goto-Kakizaki rats, sleeve gastrectomy upregulated dopaminergic machinery, showing the role of the gut in dopamine signaling in WAT. Bromocriptine treatment in the same model increased GLP-1R in WAT, showing the role of dopamine in regulating GLP-1R. By contrast, treatment with the GLP-1 receptor agonist Liraglutide had no impact on dopamine receptors. GLP-1 and dopamine crosstalk was shown in rat WAT explants, since dopamine upregulated GLP-1-induced AMPK activity in mesenteric WAT in the presence of the D2R and D3R inhibitor Domperidone. In human WAT, dopamine receptor 1 (D1DR) and GLP-1R expression were correlated. Our results point out a dietary and gut regulation of plasma dopamine, acting in the WAT to regulate GLP-1 action. Together with the known dopamine action in the pancreas, such results may identify new therapeutic opportunities to improve metabolic control in metabolic disorders.publishersversionpublishe
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