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Background: Angiogenesis plays an important role in colorectal cancer (CRC) tumorigenesis and metastatic progression. Methods: The present series consisted of CRC lymph node metastasis (LNM) tissue samples from 210 patients. Archival paraffin embedded LNM tissue were used to build up tissue microarray blocks and VEGF expression was immunohistochemically assessed. Results: VEGF-A and VEGF-C are overexpressed in LNM. VEGF-A was associated with patient age (p &lt, 0.001), and VEGFR-2 and VEGFR-3 with CRC relapse (p = 0.032, p = 0.030, respectively). VEGF-C positivity was associated with VEGFR-3 positivity (p = 0.031), and VEGF-D with VEGFR-2 and VEGFR-3 (p &le, 0.001). Matching the expression in LNM with CRC, in CRC VEGF-A positivity associates with VEGF-A, VEGF-C, VEGF-D, VEGF-R2, VEGF-R3 positivity in LNM, CRC VEGF-C with VEGF-D, VEGFR-2, VEGFR-3, CRC VEGFR-2 with VEGF-A, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3, CRC VEGFR-3 with VEGF-A, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3 in LNM. Conclusion: This study provides new information, revealing that VEGF family expression is increased in LNM. The association between the expression of VEGFR-2 and VEGFR-3 in LNM with CRC relapse reveals its impact on patient prognosis. Interesting data were found when the relationship between these proteins in primary tumor and their metastasis, were analyzed, VEGFA positivity in primary tumor is positively related to VEGF-A, VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in their respective LNM suggesting mutual influence.

The need for agile and proper identification of drugs of abuse has encouraged the scientific community to improve and todevelop new methodologies. The drug lysergic acid diethylamide (LSD) is still widely used due to its hallucinogenic effects. The use ofvoltammetric methods to analyze narcotics has increased in recent years, and the possibility of miniaturizing the electrochemical equipmentallows these methods to be applied outside the laboratory; for example, in crime scenes. In addition to portability, the search for affordable andsustainable materials for use in electroanalytical research has grown in recent decades. In this context, employing paper substrate, graphite pen-cil, and silver paint to construct paper-based electrodes is a great alternative. Here, a paper-based device comprising three electrodes was drawnon 300 g/m2watercolor paper with 8B pencils, and its efficiency was compared to the efficiency of a commercially available screen-printedcarbon electrode. Square wave voltammetry was used for LSD analysis in aqueous medium containing 0.05 mol/L LiClO4. The limits of detec-tion and quantification were 0.38 and 1.27 mol/L, respectively. Both electrodes exhibited a similar voltammetric response, which was alsoconfirmed during analysis of a seized LSD sample, with recovery of less than 10%. The seized samples were previously analyzed by GCMStechnique, employing the full scan spectra against the software spectral library. The electrode selectivity was also tested against 3,4-methylene-dioxymethamphetamine (MDMA) and methamphetamine. It was possible to differentiate these compounds from LSD, indicating that the devel-oped paper-based device has potential application in forensic chemistry analyses., Financial support provided by the Polícia Científica do Estado de São Paulo for the partnership, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP - Process 2016/23825-3), Fundação para a Ciência e Tecnologia, FCT, Portugal, (UID/QUI/00686/2016 and UID/QUI/00686/2019), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Process Capes Pro Forenses 25/2014).

A implementação das melhores evidências científicas nos serviços de saúde ainda não ocorre de forma satisfatória. Diante dessa problemática, o objetivo deste estudo foi investigar os desafios da Tradução do Conhecimento (TC) na área da saúde na atualidade. A metodologia desta revisão foi desenvolvida de acordo com os propósitos da revisão de escopo. Para tanto, as palavras-chave ‘translational medical research’ e ‘knowledge translation’ foram consultadas nos bancos de dados de periódicos da PubMed, Scopus e Web of Science. Foram incluídos os estudos publicados a partir do ano de 2008 até abril de 2018. Entre os 1.677 estudos encontrados, 839 artigos eram duplicados, e 818 não atendiam plenamente ao objetivo desta revisão; assim, 20 estudos foram submetidos à apreciação desse escopo. De acordo com as análises dos estudos, o desafio da TC advém de dois fatores: por um lado, a falta de coesão entre a comunidade científica e os tomadores de decisão em saúde; por outro, a inabilidade dos profissionais em traduzir e aplicar novos conhecimentos, além da omissão de apoio e de incentivos das instituições de saúde. Outrossim, esta revisão aborda um corpo significativo de diversos outros aspectos que limitam e/ou dificultam a TC área da saúde., The implementation of the best scientific evidence in health services has not yet occurred in a satisfactory way. Faced with this problem, the objective of this study was to investigate today’s challenges of Knowledge Translation in the health field. The methodology of this review was developed according to the requirements of the scope review. Therefore, the keywords ‘translational medical research’ and ‘knowledge translation’ were consulted in the databases of PubMed, Scopus, and Web of Science journals. Studies published from 2008 to April 2018 were included. Among the 1,677 studies found, 839 articles were duplicated and 818 did not fully meet the objective of this review, therefore, 20 studies were submitted to review and critical appraisal. According to the analysis of the studies, the challenge of Knowledge Translation comes from two factors: on the one hand, the lack of cohesion between the scientific community and health decision makers and, on the other hand, the inability of professionals to translate and apply new knowledge, in addition to the lack of support and incentives from health institutions. Furthermore, this review addresses a significant body of several other aspects that limit and/or hinder the translation of knowledge in the health field

This paper intends to make a bioethics reflection on the prolongation of human life as a consequence of the use of techniques and methods used by current medicine. The term we use is dysthanasia, however, in the anglo-american world the term medical futility is more frequently used, and for this reason we consider it synonymous with the same practice of prolonging human life with the current technical and scientific paraphernalia. The aim of this paper is to find some bioethics guidelines for the best praxis of health professionals in the clinical of end-of-life care.

Tese de doutoramento em Ciências da Saúde, Apesar dos grandes avanços e conquistas no controlo da tuberculose (TB), a doença continua a ser um importante problema de saúde pública, agravado pelo surgimento de resistência aos fármacos antituberculosos. Embora a carga da doença esteja a diminuir, é necessário acelerar este processo para atingir a meta ambiciosa de erradicação da TB até 2035, nomeadamente em Portugal. Para isso, é fundamental reavaliar e ajustar as medidas a nível nacional e local. Esta tese teve como objetivo fornecer conhecimentos sobre a emergência e transmissão da TB multirresistente (TBMR) em Portugal, visando o ajustamento das estratégias locais, de forma a prevenir e reduzir a incidência da TBMR no país. Com este propósito, e em primeiro lugar, analisamos a distribuição espacial da TBMR e TB não MR entre os municípios de Portugal, utilizando modelos espaciais Bayesianos; em segundo lugar, avaliamos a dinâmica da emergência e transmissão da TBMR, incluindo a identificação dos fatores de risco associados e estabelecemos a taxa de transmissão recente, combinando assim dados epidemiológicos e genéticos; por último, avaliamos os resultados do tratamento e identificamos os fatores associados à morte entre pacientes com TBMR e TBXDR (TB extensivamente resistente). Foram utilizados dados epidemiológicos do Sistema Nacional de Vigilância de TB (período 2000-2017) e de serviços de Saúde Pública. Encontramos heterogeneidade significativa na distribuição espacial de TBMR e TB não MR, identificamos 36 áreas de alto risco para TB não MR e 8 áreas de alto risco para TBMR. Estimamos que pelo menos 14,9% dos casos de TBMR foram atribuíveis à transmissão recente, que foi associada a indivíduos nascidos em Portugal. A taxa de sucesso do tratamento para TBMR no período em estudo foi de 77,9%. Observamos ainda que 18,4% dos pacientes com TBMR morreram durante o tratamento e, destes, 40,7% morreram nos primeiros 6 meses. A infeção pelo vírus da imunodeficiência humana foi independentemente associada à morte durante o tratamento. Desta forma, é necessário revisar e ajustar as estratégias de controlo da TB, focado na procura ativa de casos de doença e infeção latente e na deteção precoce de resistência aos fármacos, por meio de rastreio extensivo de contatos, investigação de clusters e rastreio sistemático entre grupos vulneráveis em áreas de alto risco identificadas., Despite great advances and achievements in the control of tuberculosis (TB), this disease remains an important public health problem aggravated by the emergence of resistance to anti-tuberculosis drugs. Although the disease burden is decreasing, it is necessary to accelerate this process to reach the ambitious target of eradicating TB by 2035, namely in Portugal. For this, it is essential to reassess and adjust the measures at national and local level. Thisthesis sought to provide knowledge on the emergency and transmission of multidrug-resistant TB (MDR-TB) in Portugal aiming at the adjustment of local strategies in order to prevent and reduce MDR-TB incidence in the country. For this purpose, firstly, we analyzed the spatial distribution of the MDR- and non-MDR-TB across municipalities in Portugal, using Bayesian spatial models; secondly, we assessed the dynamics of MDR TB emergence and transmission, including the identification of associated risk factors and established the rate of recent transmission, combining epidemiological and genetic data; and finally, we evaluated treatment outcomes and identified the factors associated with death among patients with MDR and XDR TB (extensively drug-resistant TB). We used epidemiological data from the national TB Surveillance System (regarding 2000-2017 period) and from Public Health services. We found significant heterogeneity in the spatial distribution of MDR- and non-MDR-TB and we identified 36 high-risk areas for non-MDR-TB and eight high-risk areas for MDR-TB. We estimated that at least 14.9% of MDR-TB cases were attributable to recent transmission, further associated with Portugal-born individuals. The estimated treatment success rate for MDR-TB was 77.9%. We observed that 18.4% of MDR-TB patients died during treatment, and, within these, 40.7% died in the first six months. Human immunodeficiency virus infection was independently associated with death during treatment. Therefore, it is necessary to review and adjust strategies for TB control, focusing on active search for cases of TB disease and latent infection, and early detection of drug-resistance, through extensive contact tracing, cluster investigations and systematic screening among vulnerable groups in identified high-risk areas., The work presented in this thesis was performed in the Life and Health Sciences Research Institute (ICVS), University of Minho. Financial support was provided by grants from the project NORTE-08-5369-FSE-000041, financed by the Operational Program NORTE 2020 and cofinanced by the European Social Fund through a doctoral grant UMINHO/BD/47/2016 and project PTDC/SAU-PUB/29521/2017; and by National funds, through the Foundation for Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020.

Tese de doutoramento em Ciências da Saúde, O envelhecimento normal é caracterizado por alterações no cérebro e na cognição, mesmo na ausência de doença. Visivelmente, as trajetórias de desempenho cognitivo no envelhecimento apresentam alta variabilidade inter-individual e vários fatores são conhecidos por contribuir para essa variabilidade. No entanto, os mecanismos neurais que provocam diferentes níveis de desempenho cognitivo em idosos ainda são mal compreendidos. O surgimento de novas ferramentas de análise na investigação em neuroimagem, tais como a análise de redes e parcelamento baseado em conectividade, pode ajudar a clarificar o envelhecimento do cérebro e as trajetórias cognitivas diferenciais. Contudo, até ao momento, poucos estudos aplicaram essas novas ferramentas para estudar alterações relacionadas com a idade nas redes cerebrais estruturais de matéria branca. O objetivo principal desta tese foi fornecer novo conhecimento sobre as mudanças induzidas pelo envelhecimento nas redes cerebrais estruturais de matéria branca e a sua associação com o estado cognitivo, através do uso de novas ferramentas de neuroimagem e estudos longitudinais. Os resultados obtidos revelaram que o envelhecimento é caracterizado por uma deterioração da integridade de matéria branca, que está associada a mudanças longitudinais na cognição. Também identificamos pela primeira vez uma sub-rede com mudanças significativas na conectividade estrutural ao longo do envelhecimento, que englobou diminuições sobretudo nas conexões intra-hemisféricas e aumentos principalmente nas conexões inter-hemisféricas. A análise das propriedades topológicas das redes cerebrais revelou uma diminuição na integração e aumento na segregação, sugerindo um cérebro mais “desconectado” com o envelhecimento. Por fim, também desenvolvemos um novo método para criar um parcelamento do cérebro baseado em conectividade e aplicámo-lo para estudar o envelhecimento do cérebro. Replicando o nosso resultado anterior, encontramos uma sub-rede com diminuições significativas nas conexões intra-hemisféricas e aumentos nas conexões inter-hemisféricas. A análise das características topológicas revelou resultados desafiadores que podem ser explicados pela maior resolução do parcelamento desenvolvido. De um modo geral, estes resultados podem ajudar a identificar os principais impulsionadores das alterações de matéria branca em diferentes níveis cognitivos, o que pode levar ao desenvolvimento de novos biomarcadores cerebrais in vivo de variabilidade inter-individual em trajetórias cognitivas., Normal aging is characterized by alterations in the brain and in cognition, even in the absence of disease. Noticeably, cognitive performance trajectories in aging exhibit high inter-individual variability and multiple factors are known to contribute to this variability. Still, the neural mechanisms which elicit different levels of cognitive performance in older adults are yet poorly understood. The emergence of new analytical tools in neuroimaging research, such as network analysis and connectivity-based parcellation, can help shed new light regarding the aging brain and the differential cognitive trajectories. However, to date few studies have applied these new tools to study age-related alterations in white matter structural brain networks. The main goal of this thesis was to provide new insights about the changes induced by aging in white matter structural brain networks and their association with cognitive status, through the use of new neuroimaging tools and longitudinal designs. Our findings revealed that aging is characterized by a deterioration of white matter integrity which is associated with longitudinal changes in cognition. We also identified for the first time a sub-network with significant changes in structural connectivity along aging, which encompassed decreases mainly in intra-hemispheric connections and increases mostly in inter hemispheric connections. The analysis of the topological properties of brain networks revealed a decrease in integration and an increase in segregation, suggesting a more “disconnected” brain along aging. Finally, we also developed a new method to create a connectivity-based parcellation of the brain and applied it to study the aging brain. Replicating our previous result, we found a sub-network with significant decreases in intra-hemispheric connections and increases in inter-hemispheric connections. The analysis of the topological features revealed challenging results which could be explained by the higher resolution of the developed parcellation. Altogether, these findings may help identify the main drivers of white matter alterations at different cognitive levels, which could lead to the development of new in-vivo brain biomarkers of inter-individual variability in cognitive trajectories., This work was financially supported by a grant of the project NORTE-08-5369-FSE-000041, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (grant UMINHO/BD/51/2017).

Trabalho de Doutoramento realizado em cotutela: Doutoramento em Envelhecimento e Doenças Crónicas e École Doctorale Cerveau, Cognition, Comportement (Paris, no 158), Chronic stress and high levels of the stress hormone, glucocorticoid (GC), are implicated in susceptibility to brain pathologies such as depression or Alzheimer’s disease (AD), as they promote neural plasticity damage and glial reactivity, which can lead to dendritic/synaptic loss, reduced neurogenesis, mood deficits, and impaired cognition. Growing clinical evidence supports a pathological link between depression and AD and shared neurobiological underpinnings with chronic stress being a potential link between them. Exposure of AD animal models to chronic stress triggers Tau pathology (e.g. Tau hyperphosphorylation and accumulation); the latter is causally related to neuronal malfunction and atrophy. Despite the well-known role of Tau in regulating cytoskeletal dynamics, the involvement of Tau in neurostructural remodeling and neuroplastic damage caused by chronic stress in the adult brain remains poorly explored. In the first objective of my thesis, we demonstrated the crucial role of Tau and its malfunction in stress-driven neurogenic, but not astrogliogenic or oligodendrogenic, damage in the cytogenic niches of the adult brain of wild-type animals (hippocampus and subventricular zone-olfactory bulb system) as mice lacking Tau were protected against stress-driven neurogenic suppression. Also, we showed that chronic stress impacts differentially the distinct phases of maturation of newborn immature neurons in the adult hippocampus. The second objective of my thesis focused on the cell-specific actions of the glucocorticoid receptor, GR, in stress-induced Tau pathology. To examine the role of GR specifically in neurons or microglia under stress conditions, we generated P301LTau mice in which GR gene is conditionally inactivated either in forebrain neurons or in microglia. Our findings show that GR was required in both cell types for chronic stress to induce cognitive deficits. Further analyses (which are ongoing) showed that neuronal GR is important in precipitating Tau neuropathology, and apical spine loss in CA1 hippocampal area. Microglial GR was found to affect microglial reactivity both in response to P301LTau as well as chronic stress-induced Tau pathology. Deletion of microglial GR results in spine loss whereas, it promotes spinogenesis under stress. However, it does not appear to impact Tau aggregation/accumulation. In conclusion, our data point to an important role of neuronal GR in mediating stress-driven Tau neuropathology and also identifies the essential role of microglial GR in stress-induced cognitive deficits. Given that the modern lifestyle increasingly exposes individuals to high stress loads, it is clear that understanding the mechanistic link(s) between chronic stress and AD pathogenesis may facilitate the treatment of AD and other related disorders., O stress crónico e as hormonas do stress, glucocorticoides, são sugeridos como causadores de suscetibilidade neuronal, estando associados a danos na plasticidade cerebral (ex. perda dendrítica/sináptica, neurogénese reduzida), inflamação, bem como a distúrbios neurológicos, como depressão e a doença de Alzheimer (DA); onde o dano da neuroplasticidade é um processo muito importante. Evidências clínicas apoiam uma ligação patológica entre a depressão e a DA, e fundamentos neurobiológicos observados no stress crónico indicam que este pode ser um fator de ligação entre elas. A exposição de modelos animais da DA a stress crónico desencadeiam patologia da proteína Tau, que parece estar relacionada com atrofia e o mau funcionamento neuronal. Tendo como função a regulação do citoesqueleto, a proteína Tau tem um papel importante e inexplorado na remodelação neuroestrutural e nos danos neuroplásticos provocados pelo stress crónico. No primeiro objetivo desta Tese, demonstramos a importância da proteína Tau e o impacto do seu mau funcionamento, causado pelo stress, nos nichos citogénicos do cérebro adulto, com impacto na neurogénese, mas não na astrogliogénese ou oligodendrogénese; pois animais sem a proteína Tau são protegidos contra a supressão neurogénica induzida pelo stress crónico. No segundo objetivo, focamo-nos nas ações do receptor de glucocorticoides (GR) na patologia Tau induzida pelo stress, em tipos celulares específicos. Para isso, geramos murganhos P301LTau com deleção condicional de GR em neurónios ou em microglia. Os resultados mostram que o GR é necessário para a indução de danos cognitivos derivados do stress crónico. O GR neuronal é importante para a precipitação da neuropatologia da Tau bem como para a perda de espinhas apicais na zona CA1 do hipocampo. A deleção de GR na microglia levou à sua reatividade, bem como à perda de espinhas, mas com o stress crónico promoveu a sua génese. A mesma não afetou a agregação/acumulação da proteína Tau. Desta forma, concluímos que os nossos dados apontam para o importante papel do GR neuronal na meadiação da neuropatologia da Tau e identificamos o papel essencial do GR na microglia para a indução de danos cognitivos. Dado que o estilo de vida moderno expõe cada vez mais os indivíduos a altas cargas de stress, é clara a necessidade de compreender melhor a ligação entre o stress crónico e a patogénese da DA, facilitando o tratamento da DA e de outros distúrbios., The work presented in this thesis was performed in the Life and Health Sciences Research Institute (ICVS), University of Minho, Portugal and in the Institute of Biology Paris Seine (IBPS), Sorbonne University, France. Financial Support was provided by a Ph.D. fellowship (PD/BD/127825/2016) from the FCT – Foundation for Science and Technology. This Ph.D. has also been funded by National funds, through the Foundation for Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020; and by the projects, NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, the Project Estratégico co-funded by FCT (PEst-C/SAU/LA0026/2013) and the European Regional Development Fund COMPETE (FCOMP-01-0124-FEDER-037298; POCI-01-0145-FEDER-007038) supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). We acknowledge support from PAULIF, a bilateral “Luso-France Integrated Actions” program and to “France Alzheimer et Maladies Apparentées” program.

Este ensaio tem como objetivo refletir sobre a Educação Física (EF) escolar como campo do conhecimento com responsabilidades de propor uma formação para o “tempo do inútil”. Ao longo do texto, procuramos demonstrar que, em tempos de crise, utilitarismos e imediatismos, reconhecer a importância de uma formação para o “tempo do inútil” representaria uma virada paradigmática para a EF, especialmente no contexto escolar., This essay aims reflect on the school Physical Education (PE) as a field of knowledge with responsibilities of propose a formation for the "useless time". Throughout the text, we tried to demonstrate that, in times of the crisis, utilitarianisms and immediacies, recognizing the importance of a culture for "useless time" would represent a paradigm change for PE, especially in the school context., Este ensayo apunta a reflexionar sobre la Educación Física (EF) escolar como un campo del conocimiento con responsabilidades de proponer una formación para el "tiempo de lo inútil". A lo largo del texto, tratamos de demostrar que, en tiempos de crisis, utilitarismos e imediatismos, reconocer la importancia de una cultura por "tiempo de lo inútil" representaría un cambio de paradigma para la EF, especialmente en lo contexto escuelar.

Tese de doutoramento em Ciências da Saúde, Visceral leishmaniasis (VL) is a neglected tropical disease caused by parasites of the genus Leishmania, particularly L. donovani and L. infantum, and can be fatal if untreated. Although several available therapies are described for VL, the associated high costs, efficacy problems, and the high numbers of relapsing cases point this disease as one of the neglected tropical diseases for which the development of new treatments is a priority. Metabolic reprogramming of immune cells is well described in infectious diseases. Several reports have shown that Leishmania infection profoundly affects host cell metabolism, which is intimately correlated with intracellular parasite survival. While neutrophils are essential to early infection, the long-lasting Leishmania infection is established within macrophages. Thus, in this thesis, we proposed to characterize the metabolic networks regulating VL on macrophages and its relation to the anti-leishmanial immune response. Therefore, we combined the use of in vitro and in vivo models of L. donovani infection with different analysis methods (RNA sequencing, metabolomics, multiparametric flow cytometry analysis, gene expression profiling, and protein quantification). Leishmania-infected macrophages rely on glucose metabolism to control parasite growth during early infection. In parallel, we uncover a relevant role for L- glutamine metabolism in L. donovani-infected macrophages. We observed a metabolic signature of increased glutaminolysis on L. donovani-infected macrophages, whose pharmacological inhibition significantly increased the susceptibility to infection. Importantly, we have demonstrated that glutamine-miltefosine synergy is a novel combined host- and pathogen-directed treatment for combating VL. Transcriptomic and metabolomic analyses performed at later times of infection indicated that L. donovani parasites further impact the host metabolome by modulating lipid metabolism-associated pathways. Overall, our data contribute to elucidate the capacity of Leishmania parasites to manipulate host cell metabolome towards an appropriate immunometabolic environment for their survival inside the host, which can be continuously changing along with the course of the infection. Deciphering these queries is of great value to understand how Leishmania parasites can hijack host metabolism to persist inside the host and the mechanisms underlying its adaptation., A leishmaniose visceral é uma doença tropical negligenciada causada por parasitas do gênero Leishmania, particularmente Leishmania donovani e Leishmania infantum. Embora várias terapias estejam disponíveis para o tratamento deste tipo de patologia, problemas de eficácia e o grande número de recidivas fazem desta doença uma das doenças tropicais negligenciadas para a qual o desenvolvimento de novos tratamentos é uma prioridade. A reprogramação metabólica das células imunológicas está amplamente descrita em doenças infeciosas. Vários estudos têm demonstrado alterações no metabolismo da célula hospedeira após infeção por Leishmania, estando esta alteração intimamente relacionada com a sobrevivência do parasita. Embora os neutrófilos sejam extremamente importantes no início da infeção, o estabelecimento da infeção é determinado pelos macrófagos. Deste modo, o principal objetivo desta tese é caracterizar as redes metabólicas que regulam a leishmaniose visceral em macrófagos e sua relação com a resposta imune do hospedeiro. Assim, combinamos o uso de modelos in vitro e in vivo de infeção por L. donovani com diferentes métodos de análise (sequenciação de RNA, metabolómica, citometría de fluxo, perfil de expressão gênica e quantificação de proteínas) para compreender de que forma estes parasitas podem modular o metabolismo celular de forma a permanecer dentro do hospedeiro. O nosso trabalho demonstrou que macrófagos infetados dependem do metabolismo glicolítico para controlar o crescimento dos parasitas no início da infeção. Além disso, também identificamos um papel relevante para o metabolismo da L-glutamina em macrófagos infetados com L. donovani. Macrófagos infetados apresentavam uma assinatura metabólica de aumento da glutaminólise, cuja inibição farmacológica aumentou significativamente a suscetibilidade à infeção. Além disso, demonstramos que a utilização de uma terapia combinada baseada na utilização de L-glutamina durante o tratamento com miltefosina, poderá representar uma nova terapia dirigida ao hospedeiro e ao patógeno para combater a Leishmaniose visceral. Análises de transcripótmica e metabolómica realizadas em momentos tardios de infeção indicaram que estes parasitas alteram o metaboloma do hospedeiro ao modular vias associadas com o metabolismo lipídico. Os nossos dados contribuem para elucidar a capacidade deste parasita em manipular o metaboloma da célula hospedeira criando um ambiente imunometabólico adequado para sua sobrevivência., The financial support of this work was provided by grants from the Foundation for Science and Technology (FCT, Portugal)/FEDER (PD/BDE/127830/2016 and Infect-Era Net (project INLEISH)), and by National funds, through the same foundation - project UIDB/50026/2020 and UIDP/50026/2020; and by the projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)

Tese de doutoramento em Ciências da Saúde, A major contributor for the severe deficits spinal cord injury (SCI) patients face lies on the disruption of the blood-spinal cord barrier (BSCB), and consequent deficient angiogenic response. Therefore, during this PhD thesis we proposed to develop vascularizable cell transplantation vehicles based on modified gellan gum (GG) hydrogels aiming to promote SCI repair. We started by understanding whether human umbilical vein endothelial cells (HUVECs) were able to assemble into vascular-like constructs when cultured on in-house GRGDS-modified GG (GG-GRGDS). HUVECs only developed stable vascular-like constructs in the presence of adipose-derived stem cells (ASCs). Moreover, the co-culture secretome had an enrichment on defined neurotrophic factors in comparison to the individual culture of both types of cells. We also observed a significant promotion on axonal growth in comparison to the hydrogels without cells. The next part of the work involved the modification of GG with two integrin-specific ligands (against αvβ3 and α5β1) to improve the bioactivity of the polymer. Cell adhesion studies showed that the αvβ3 mimetic promoted significant adhesion of ASCs to the matrix in comparison to RGD and the other mimetic ligand. This was even more evident for the formulation modified using a GG:ligand ratio of 10:1 (GGp10αv). Despite integrin specificity, it were only observed vascular-like structures only when HUVECs were co-cultured with ASCs. The axonal growth experiments did not reveal a statistical increase when comparing the co-culture with the hydrogel alone. Finally, the in vivo evaluation of both in-house GG-GRGDS and GGp10αv on a T8 transection model of SCI showed statistically significant motor improvements for GGp10αv encapsulating ASCs+HUVECs in comparison to lesioned animals. Furthermore, both GG-GRGDS and GGp10αv (with and without cells) lead to significant gains of sensation 8 weeks after SCI. It was also observed that during the acute phase of SCI GGp10αv+cells promoted a marked decrease on pro-inflammatory cytokines such as IL-1 α, IL-1 β, TNF-α and MCP-1 that are associated with the exacerbation of damage following SCI. On the other hand, IL-10 and IL-4, which are more connected to a pro-regenerative inflammation, were augmented relative to injured animals. Even though the histological and proteomic characterization of the tissue is still lacking, these indications point out towards a neuroprotective effect of GGp10αv+cells on injured tissue., Um dos principais contribuintes para os défices observados em pacientes com lesões medulares é a disrupção da componente medular da barreira hematoencefálica, e consequente resposta angiogénica defetiva. Assim, nesta tese propusemos o desenvolvimento de veículos de transplantação celular vascularizáveis baseados em hidrogéis de goma gelano modificado, com o pressuposto de promover a recuperação depois de lesão medular. Começámos por entender se células endoteliais do cordão umbilical (HUVECs) se organizavam em estruturas vasculares quando encapsuladas em GG modificado com GRGDS. Observámos que as HUVECs apenas apresentaram este fenótipo quando encapsuladas em co-cultura com células estaminais derivadas de tecido adipose (ASCs). A análise do secretoma da co-cultura mostrou um enriquecimento em factores neurotróficos definidos em comparação com a cultura isolada de ambas as células. Também se observou uma promoção significativa no crescimento axonal em comparação com os hidrogéis sem células. A próxima parte do trabalho envolveu a modificação de GG com dois ligandos específicos para integrinas (αvβ3 e α5β1) de modo a melhor a bioatividade do polímero. Estudos de adesão cellular mostraram que o mimético para αvβ3 promoveu adesão significativa de ASCs em comparação com o RGD e o outro ligando mimético. Isto foi ainda mais evidente para a formulação que usou um rácio GG:ligando de 1:10 (GGp10αv). Apesar da elevada especificidade, só se observaram estruturas vasculares quando as ASCs estavam em co-cultura com as HUVECs. As experiências de crescimento axonal não revelaram aumentos estatísticos quando comparando a co-cultura com hidrogel sem células. Finalmente, a avaliação in vivo da co-cultura em GGp10αv, num modelo de transecção em T8, levou a melhorias motoras significativas em comparação ao grupo lesionado. Além disso, tanto o GG-GRGDS como o GGp10αv promoveram ganhos sensoriais significativos às 8 semanas. Durante a fase aguda da condição o GGp10αv+células promoveu uma diminuição de citocinas pro-inflamatórias como IL-1 α, IL-1β, TNF-α e MCP-1. Por outro lado, citocinas ligadas a uma resposta inflamatória mais regenerativa como IL-10 e IL-4 estavam aumentadas em comparação com animais lesionados. Apesar de a caracterização histológica e proteómica do tecido estar em falta, estas indicações apontam para um efeito neuroprotetor promovido pela condição experimental GGp10αv+células no tecido medular lesionado., Financial support was provided by National funds, through the Foundation for Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020; and by the projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Prémios Santa Casa Neurociências ‐ Prize Melo e Castro for Spinal Cord Injury Research (MC-04/17). FEDER, through the Competitiveness Internationalization Operational Program (POCI), and by National funds, through the FCT, under the scope of the projects POCI-01-0145-FEDER-007038; TUBITAK/0007/2014; PTDC/DTP-FTO/5109/2014; POCI-01-0145-FEDER-029206; POCI-01-0145-FEDER-031392; PTDC/MED-NEU/31417/2017. LR is acknowledges FCT by the finantial support (PD/BDE/127835/2016)

Tese de doutoramento em Envelhecimento e Doenças Crónicas, In 2019, malaria caused half a million deaths worldwide, being elimination hampered by the ability of Plasmodium falciparum to evolve antimalarial resistance. The efficacy of artemisinin-based combination therapies (ACT) helped to reduce malaria mortality, however, resistance is a reality. Being ACT efficacy threatened, efforts to define the molecular basis of multidrug resistance and the search for new compound, ideally with new mechanisms of action, are urgently in need. Within the parasite, most of the available antimalarials act at the host’s intraerythrocytic stage. Here, many drugs are housed in the digestive vacuole of the parasite with flux promoted by transporter proteins, such as the Plasmodium falciparum multidrug resistance protein 1 (PfMDR1), a well-known ACT resistance player. We explored the interplay of known pfmdr1 resistance markers, namely, gene copy number variation with N86Y and Y184F single nucleotide polymorphisms to unravel the complex traits that might serve to maximize ACT resistance. Using genomic epidemiology, a global prevalence and temporal changes of pfmdr1 polymorphisms were assessed and, taking into account the information from this database, through a gene editing approach, we create in vitro edited parasite lines to evaluate the impact of these polymorphisms in the kinetics of the transporter. This data provided evidence of specific multicopy PfMDR1 with N86/184F haplotype, geographic selection and expansion in Southeast Asia. The genetic tools created could help on finding drugs with potential of reverting a multidrug resistance phenotype, as the herein explored synthetic compounds derived from steroids, a class of molecules with relevant biological activities. Structure–activity relationship led to the synthesis of steroid derivatives with promising antimalarial activity against the blood stage of the parasite’s life cycle with high selectivity and independent of PfMDR1. Exploring possible mechanisms of action of the best compound, revealed induction of oxidative stress inside the parasite and interference with the metabolic process that leads to hemozoin formation inside the digestive vacuole of the parasite. Overall, the findings presented could help tailor and optimize present antimalarial drug usage by taking into account the regional prevalence of pfmdr1 polymorphisms and highlights the high potential of the newly developed compounds, thereby underscoring the possibility to develop new antimalarial drugs based on steroids., Em 2019, a malária causou meio milhão de mortes mundialmente, sendo a eliminação dificultada pela capacidade do Plasmodium falciparum desenvolver resistência aos antimaláricos atuais. A eficácia da terapia de combinação baseadas em artemisinina (ACT) ajudou a reduzir a mortalidade provocada pela malária, no entanto, a resistência é uma realidade. A eficácia do ACT está comprometida, as tentativas para definir as bases moleculares da multirresistência e a procura por novos compostos, idealmente com novos mecanismos de ação, são urgentes. No parasita, a maioria dos antimaláricos atua no estadio intra-eritrocítico. Muitos são alojados no vacúolo digestivo do parasita através do fluxo promovido por proteínas transportadoras, como a “Plasmodium falciparum multidrug resistance protein 1” (PfMDR1), um fator envolvido na resistência aos ACTs. Neste trabalho foi explorada a interação de marcadores de resistência conhecidos no pfmdr1, ou seja, variação do número de cópias do gene com polimorfismos no nucleótido N86Y e Y184F para tentar descobrir as características que ajudam a maximizar a resistência aos ACTs. Usando epidemiologia genómica, a prevalência e alterações temporais dos polimorfismos no pfmdr1 foram avaliadas tendo em consideração a informação obtida desta base de dados, através de edição de genes, geramos in vitro parasitas editados para avaliar o impacto desses polimorfismos na cinética do transportador. Isto desvendou evidências acerca do haplótipo específico de multicópias com N86/184F, sobre a seleção geográfica e expansão no Sudeste Asiático. As ferramentas genéticas criadas podem auxiliar na descoberta de fármacos com potencial para reverter o fenótipo de resistência, como os compostos sintéticos derivados de esteróides explorados nesta tese, uma classe de moléculas com atividade biológica relevante. A relação estrutura-atividade levou à síntese de esteróides com uma atividade promissora contra o estadio intra-eritrocítico do ciclo de vida do parasita com grande seletividade e independência do PfMDR1. Os mecanismos de ação do melhor composto foi também explorados, revelando indução de stress oxidativo no parasita e uma interferência no processo metabólico que leva à formação de hemozoína. Concluindo, os resultados apresentados podem ajudar a adaptar e otimizar o uso dos antimaláricos atuais, tendo em consideração a prevalência regional dos polimorfismos no pfmdr1 e, destaca também o grande potencial dos compostos recentemente desenvolvidos, demonstrando a possibilidade de desenvolver novos antimaláricos baseados em esteróides., Financial support was provided by grants from the PD/BD/127826/2016, ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122; by National funds, through the Foundation for Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020; by the projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)

Tese de Doutoramento em Engenharia Química e Biológica, Os lipossomas são considerados um sistema de entrega adequado para vários fármacos. O nosso grupo de investigação desenvolveu uma formulação lipossomal com metotrexato (MTX), a primeira linha de tratamento da artrite reumatoide (AR). Os lipossomas têm uma estratégia inovadora de direcionamento por folato, recorrendo a um péptido hidrofóbico, que tem como alvo o recetor de folato β presente na superfície de macrófagos ativados, células efetoras chave na AR. Estes lipossomas acumulam-se nas articulações de ratinhos com artrite, melhorando as pontuações clínicas comparativamente a ratinhos que recebem MTX livre. Estes resultados conduziram ao desenvolvimento do projeto europeu FOLSMART, com ênfase no desenvolvimento não-clínico e ensaios clínicos de fase I. O trabalho desenvolvido no meu doutoramento está inserido neste projeto, tendo como objetivo otimizar a produção de lipossomas com MTX e completar os ensaios não-clínicos em ratinhos com artrite, de modo a alcançar a implementação do ensaio clínico em humanos. Primeiramente, foi estabelecido um método apropriado para a quantificação de fármacos encapsulados nos lipossomas, explorando as vantagens da espectrometria de ressonância magnética nuclear (RMN). Após determinar a concentração de um fármaco hidrofóbico e outro hidrofílico recorrendo ao uso de um padrão interno, foi realizado um estudo comparativo com duas técnicas tradicionais para validar os resultados obtidos por RMN. O armazenamento da formulação lipossomal a longo prazo também foi estudado, através da incorporação de sacarose como crio e lioprotetor, de modo a preservar a integridade do lipossoma após o processo de liofilização. Lipossomas com o fármaco localizado na bicamada lipídica apresentaram perdas insignificantes de fármaco, preservando a sua atividade biológica após o processo de liofilização. De seguida, o trabalho focou-se no aumento de MTX encapsulado nos lipossomas, através do desenvolvimento e otimização de um novo método de produção, baseado nos princípios do método de injeção etanólica. Os lipossomas obtidos apresentam valores pequenos de tamanho e índice de polidispersividade (sem extrusão), alta encapsulação de MTX e um aumento do benefício clínico em ratinhos com artrite. No final, foram realizadas experiências em ratinhos com artrite de modo a completar os ensaios não-clínicos. O melhor rácio fármaco-lípido de lipossomas direcionados por folato encapsulando MTX foi determinado, bem como a dose necessária para se obter efeito terapêutico. Além disso, foi avaliado o padrão de biodistribuição e a via de injeção subcutânea. Em resumo, este trabalho apresenta resultados que permitem a implementação do ensaio clínico em humanos, demonstrando que lipossomas direcionados por folato constituem um sistema promissor de entrega de MTX para o tratamento de AR., Liposomes are considered a suitable drug delivery system for several drugs. Our research group developed a liposomal formulation encapsulating methotrexate (MTX), the first-line therapy of rheumatoid arthritis (RA). The liposomes have an innovative strategy for folate-targeted delivery, using a hydrophobic peptide, that targets folate receptor β (FRβ) present at the surface of activated macrophages, key effector cells in RA. These liposomes showed a stronger accumulation at paws of arthritic mice, improving clinical scores compared to those receiving unformulated MTX. These results pave the way to develop the European project FOLSMART, emphases on the non-clinical development and phase I clinical trials. The work developed in my PhD is inserted in this project, aiming to optimize the production of liposomes encapsulating MTX and complete the nonclinical package in arthritic mice to further reach the implementation of the First-in-Human (FiH) clinical trial. Opening findings involved the establishment of an appropriate method for drug quantification inside liposomes, exploiting the advantages of 1H Nuclear Magnetic Resonance (NMR) spectrometry. After determining the concentration of a hydrophobic and a hydrophilic drug using an internal standard, a comparative study was performed with two traditional techniques to validate the results obtained by 1H NMR. A suitable approach to long-term storage of the liposomal formulation was also addressed, by incorporation of sucrose as cryo and lyoprotectant, to preserve its integrity after the freeze-drying process. Liposomes with a drug located in the lipid bilayer demonstrated negligible leakage preserving their biological activity after the freeze-drying process. Following efforts were dedicated on increasing MTX encapsulated inside liposomes through the development and optimization of a novel production method, based on the principles of the ethanol injection method. The liposomes obtained present small values of size and polydispersity index (without extrusion), a higher MTX encapsulation and increases the biological benefit in arthritic mice. At the end, a set of deeper experiments were performed in collagen-induced arthritis (CIA) mice model to complete the nonclinical package. The better drug-to-lipid ratio of folate-targeted liposomes encapsulating MTX was determined as well as the dosage needed to obtain a therapeutic effect in CIA mice. Furthermore, the biodistribution pattern was evaluated as well as the subcutaneous injection route. In summary, this PhD work present findings that allow the implementation of the FiH clinical trial, demonstrating that folate-targeted liposomes constitute a promising MTX delivery system for RA treatment., Fundação para a Ciência e a Tecnologia (FCT), Projeto Europeu FOLSMART

Tese de doutoramento em Engenharia Química e Biológica, A vaginose bacteriana (VB), a causa mais comum de distúrbio vaginal, está associada a complicações ginecológicas e obstétricas graves. Durante a VB, um biofilme polimicrobiano é formado no epitélio vaginal, formado principalmente por espécies de Gardnerella, mas contendo também diversos outros microrganismos anaeróbios. No entanto, pouco se sabe sobre o papel destes microrganismos no desenvolvimento de VB, sendo, no entanto, evidente que os biofilmes polimicrobianos de VB apresentam uma maior capacidade de sobreviver ao tratamento clássico por antibióticos. Por essa razão, a busca por novas terapias contra VB tem vindo a aumentar. Nesta tese, investigou-se as interações entre Gardnerella vaginalis e outras espécies associadas à VB, com o objetivo de compreender como estas interações afetam a formação de biofilmes e qual o impacto no tratamento antimicrobiano. Foram usados dois modelos distintos de formação de biofilmes triplos, o que permitiu concluir que, in vitro, G. vaginalis é a espécie microbiana que constituiu a maior parte da biomassa de todos os consórcios testados, em ambos os modelos. Verificou-se também que, em alguns dos consórcios, a capacidade antimicrobiana quer de antibióticos comuns, quer do óleo essencial (OE) obtido da planta Thymbra capitata, sofreram reduções de atividade, o que ajuda a explicar a elevada taxa de recorrência nos casos de VB. No global deste estudo, destacou-se (i) o papel central da Gardnerella na formação de biofilmes polimicrobianos associados à VB, (ii) como as interações entre bactérias em biofilmes polimicrobianos impactam a formação de biofilme e a suscetibilidade antimicrobiana, e (iii) o potencial antimicrobiano do OE de T. capitata contra biofilmes polimicrobianos associados à VB. Os resultados obtidos nesta tese podem ajudar a desenvolver novas abordagens terapêuticas com base em OE de T. capitata, a fim de prevenir VB e reduzir a sua recorrência., Bacterial vaginosis (BV), the most common cause of vaginal discharge, is associated with serious gynaecologic and obstetric complications. The hallmark of BV is the presence of a polymicrobial biofilm on the vaginal epithelium, presumably initiated and mainly formed by Gardnerella species. However, the BV biofilm is also populated by many other anaerobes, but very little is known about their role in BV development. It has been shown that this polymicrobial biofilm may increase the survival of Gardnerella and other BV-associated species when exposed to antibiotics, as such causing high recurrence rates of BV. This triggered the interest in exploring agents that have been claimed to disrupt biofilms, such as plant-derived products, namely Thymbra capitata essential oil (EO). In this thesis, we investigated the interactions between Gardnerella vaginalis and other BV-associated species in BV biofilms, aiming to understand how they impact BV development and treatment outcome. First, two in vitro triple-species biofilm formation models were used, with and without allowing G. vaginalis to form an early biofilm before adding the other two species. The data from this study revealed that independent of the model used, all species were able to form triple-species biofilms, in which G. vaginalis was always the predominant species. Interestingly, we observed that in some triple-species consortia, synergistic interactions affected the antibiotic treatment outcome, leading to an enhanced tolerance. Second, when applying T. capitata EO against multi-species biofilms consisting of six cultivable BVassociated species, we observed that the interactions between the species also influenced, to some extent, the EO antimicrobial activity. The data collected in this study further highlight (i) the pivotal role of Gardnerella in BV polymicrobial biofilms, (ii) how interactions between bacteria in multi-species biofilms impact the biofilm formation and antimicrobial susceptibility, and (iii) the antimicrobial potential of T. capitata EO against multi-species BVassociated biofilms. These findings could help to further shape novel treatment approaches based on T. capitata EO in order to prevent BV and reduce its recurrence., This study was supported by the Portuguese Foundation for Science and Technology (FCT) through an individual PhD scholarship (PD/BD/128037/2016), the research project PTDC/BIA-MIC/28271/2017 under the scope of COMPETE 2020 (POCI-01-0145-FEDER-028271) and the strategic funding of UIDB/04469/2020 unit.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is a neurodegenerative disorder caused by a polyglutamine expansion in the ATXN3 gene. In spite of the identification of a clear monogenic cause 25 years ago, the pathological process still puzzles researchers, impairing prospects for an effective therapy. Here, we propose the disruption of protein homeostasis as the hub of SCA3 pathogenesis, being the molecular mechanisms and cellular pathways that are deregulated in SCA3 downstream consequences of the misfolding and aggregation of ATXN3. Moreover, we attempt to provide a realistic perspective on how the translational/clinical research in SCA3 should evolve. This was based on molecular findings, clinical and epidemiological characteristics, studies of proposed treatments in other conditions, and how that information is essential for their (re-)application in SCA3. This review thus aims i) to critically evaluate the current state of research on SCA3, from fundamental to translational and clinical perspectives; ii) to bring up the current key questions that remain unanswered in this disorder; and iii) to provide a frame on how those answers should be pursued., The authors thank all the members of the Maciel lab for their helpful tips and discussion. This work was funded by the European Regional Development Fund (FEDER), through the Competitiveness Internationalization Operational Programme (POCI), and by national funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-0 31987. Moreover, the work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the FEDER (project NORTE-01-0145-FEDER-000013). A fellowship supporting the development of this work was attributed by FCT to J. D. Da S. (PD/BD/128074/2016).

As mudanças curriculares, a inserção das novas tecnologias, o contexto social e as condições econômicas e políticas da sociedade moderna afetam o processo de formação de professores. Partindo deste entendimento, este trabalho apresenta análises, discussão e significação da Educação em Saúde (ES), na formação inicial e continuada de professores, com uso do filme comercial “Uma Prova de Amor (EUA, 2009)”. A questão orientadora foi: que aprendizagens em educação em saúde são produzidas na discussão de filmes comerciais, em aulas da educação básica ou superior? Vinte e seis professores de Ciências Biológicas, em formação inicial e continuada, com reuniões formativas sistemáticas, participaram de sete sessões fílmicas. Em cada uma delas, o grupo assistia a um filme e discutia as compreensões de saúde e educação em saúde. As sessões foram audiogravadas, transcritas, lidas e identificados os excertos significativos. A Análise Microgenética das transcrições das discussões produzidas mostrou que o debate e as interações no grupo possibilitaram ampliar e ressignificar o entendimento de saúde numa articulação de aspectos anatômicos, fisiológicos e bioquímicos, sociais, emocionais e ambientais. Além disso, questões como finitude da vida, eutanásia, direito a morte digna e envelhecimento foram contempladas na discussão, ampliando a compreensão da promoção da saúde., Curricular changes, the insertion of new technologies, the social context and the economic and political conditions of mo-dern society affect the process of teacher training. Based on this understanding, this work presents the analysis, discussion and significance of Health Education (HE), in the initial and continuing teacher training, using the commercial film “My Sis-ter’s Keeper (USA, 2009)”. The guiding question was: what learning in health education is produced in the discussion of com-mercial films, in classes of basic and higher education? Twenty-six teachers of Biological Sciences, in initial and continuing training, with systematic training sessions, participated in seven film sessions. In each session, the group watched a film and discussed the understandings of health and health education. The sessions were audio-recorded, transcribed, read and the significant excerpts were identified. The Microgenetic Analysis of the transcripts of the discussions produced, showed that the debate and interactions in the group made it possible to broaden and re-signify the understanding of health in an articu-lation of anatomical, physiological and biochemical, social, emotional and environmental aspects. In addition, issues such as finitude of life, euthanasia, right to dignified death and aging were addressed in the discussion, broadening the understan-ding of health promotio, Fundos nacionais através da FCT (Fundação para a Ciência e a Tecnologia) no âmbito do projeto do CIEC (Centro de Investigação em Estudos da Criança) da Universidade do Minho, com a referência UID/CED/00317/2019

Tese de doutoramento em Ciências da Saúde, Tuberculosis is a global health problem and a destructive disease associated with high morbidity and mortality. Accurate early diagnosis and correct treatment would deeply contribute to worldwide control, but diagnosis is challenging. Results of chest radiography and tuberculin tests are unspecific and ambiguous, and the conventional laboratory approaches are, in some situations, insufficient for a precise diagnosis. Antigen detection platforms could provide simple and rapid diagnosis, however these tests present variable accuracy and cross-reactivity. The solution to these problems could be provided by the labeling of antibodies with nanoparticles, because magnetic nanoparticles can be manipulated and accurately detected by external magnetic fields, and antibodies provide target specificity and selective recognition. In the scope of the research presented throughout this dissertation, a new method towards a point-of-care diagnosis for tuberculosis was investigated. Streptavidin capped magnetic nanoparticles were bioconjugated with biotinylated antibodies that capture surrogate bacteria, and a magnetoresistive platform was used to detect labeled biomolecules at the biochip surface, previously functionalized with specific and control antibodies. Results confirmed the viability of this sandwich-type immunoassay technique, and experimental evidence for validating a proof-of-concept on specificity and quantification abilities of the magnetoresistive biosensor was provided by chemometrics and other signal correction methods, deriving the current state of the technology as a potential alternative test. The main goal of this PhD thesis is to provide significant developments towards the existence of a useful and effective alternative for the point-of-care diagnosis of tuberculosis, applying magnetic nanoparticles biofunctionalized with specific antibodies, which can be detected by a magnetoresistive biosensor platform previously developed at INESC MN., A tuberculose é um importante problema de saúde mundial e uma doença destrutiva associada a elevada morbilidade e mortalidade. Um diagnóstico precoce fiável e um tratamento adequado poderiam contribuir decisivamente para o controlo da tuberculose a nível mundial, mas isto é ainda um desafio. Os resultados de raio-X torácico e os testes de tuberculina são inespecíficos e ambíguos, e as abordagens laboratoriais convencionais são, em algumas situações, insuficientes para um diagnóstico preciso. Os testes de deteção de antigénio podem fornecer um diagnóstico simples e rápido, mas apresentam fiabilidade variável e reatividade cruzada. A solução para estes problemas poderia passar pela marcação de anticorpos com nanopartículas, porque as nanopartículas magnéticas podem ser manipuladas e detectadas com precisão por campos magnéticos externos e os anticorpos oferecem especificidade e reconhecimento seletivo. No âmbito do trabalho experimental apresentado ao longo da dissertação, investigou-se um novo método para o diagnóstico point-of-care de tuberculose. Foram usadas nanopartículas magnéticas com estreptavidina para bioconjugar anticorpos biotinilados que capturam bactérias em solução, e uma plataforma magnetoresistiva para detectar estas biomoléculas marcadas na superfície do biochip, previamente funcionalizada com anticorpos específico e controlo. Os resultados confirmaram a viabilidade desta técnica de imunoensaio tipo sanduíche, e as evidências experimentais validaram a prova de conceito para especificidade e quantificação do biosensor, por quimiometria e outros métodos de correção de sinal, derivando o atual estado da tecnologia como um possível teste alternativo. O principal objectivo desta tese de doutoramento é fornecer desenvolvimentos significativos no sentido da criação de uma alternativa útil e eficaz para o diagnóstico da tuberculose, aplicando nanopartículas magnéticas funcionalizadas com anticorpos específicos, mediante a detecção de um biosensor magnetoresistivo previamente desenvolvido no INESC MN.

Multisite neural probes are a fundamental tool to study brain function. Hybrid silicon/polymer neural probes combine rigid silicon and flexible polymer parts into one single device and allow, for example, the precise integration of complex probe geometries, such as multishank designs, with flexible biocompatible cabling. Despite these advantages and benefiting from highly reproducible fabrication methods on both silicon and polymer substrates, they have not been widely available. This paper presents the development, fabrication, characterization, and in vivo electrophysiological assessment of a hybrid multisite multishank silicon probe with a monolithically integrated polyimide flexible interconnect cable. The fabrication process was optimized at wafer level, and several neural probes with 64 gold electrode sites equally distributed along 8 shanks with an integrated 8 µm thick highly flexible polyimide interconnect cable were produced. The monolithic integration of the polyimide cable in the same fabrication process removed the necessity of the postfabrication bonding of the cable to the probe. This is the highest electrode site density and thinnest flexible cable ever reported for a hybrid silicon/polymer probe. Additionally, to avoid the time-consuming bonding of the probe to definitive packaging, the flexible cable was designed to terminate in a connector pad that can mate with commercial zero-insertion force (ZIF) connectors for electronics interfacing. This allows great experimental flexibility because interchangeable packaging can be used according to experimental demands. High-density distributed in vivo electrophysiological recordings were obtained from the hybrid neural probes with low intrinsic noise and high signal-to-noise ratio (SNR)., This work has been funded by: national funds through the Foundation for Science and Technology (FCT)—projects UIDB/50026/2020 and UIDP/50026/2020; the projects NORTE-01-0145- FEDER-000013 (“PersonalizedNOS—New avenues for the development of personalized medical interventions for neurological, oncologic and surgical disorders”) and NORTE-01-0145-FEDER-000023 (“FROnTHERA—Frontiers of technology for theranostics of cancer, metabolic and neurodegenerative diseases”), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI— Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122); FCT project PTDC/MEDNEU/ 28073/2017 (POCI-01-0145-FEDER-028073); and The Branco Weiss fellowship—Society in Science, (ETH Zurich).

"Available online 24 November 2020", Background: The Fresno Test was originally identified as an instrument to assess evidence-based practice knowledge and skills through cognitive testing and performance assessment in medical students. Further studies have been recommended to establish the measurement properties of the Fresno Test in different learner populations. Objectives: To perform a cross-cultural adaptation of the Fresno Test for Portuguese undergraduate nursing students and to analyze the interrater reliability. Design: Cross-cultural adaptation study with interrater reliability assessment carried out in two phases during 2017–2018. Settings: One of the main nursing schools, Portugal. Participants: Fourth year undergraduate nursing students. Methods: The study was performed in two phases, firstly the cross-cultural adaptation (performed in five stages) and secondly the analysis of interrater reliability. Results: Stages I, II, III and IV of the cross-cultural adaptation proceeded smoothly and the expert panel produced and agreed upon the pre-final version of Adapted Fresno Test. In stage V (the pre-test stage), students reported a general understanding of the items, but they reported a lack of knowledge to answer the test. An expert panel subsequently agreed that modifications were needed to ensure the test was within the student’s competency level and to decrease risk of assessment bias. For phase II, 50 complete questionnaires were randomly selected to be rated by three independent nurses using the modified rubric to score the test. The overall interrater reliability was 0.826 with a range from 0.271 to 1.000 for each item. Conclusions: The Adapted Fresno Test presented in this paper is the first instrument translated for European Portuguese and adapted specially for undergraduate nursing students. Despite good interrater reliability, further validation studies with more robust samples are suggested to definitively establish psychometric properties beyond the interrater reliability., The authors gratefully acknowledge the support of Health Sciences Research Unit:Nursing (UICISA: E), hosted by the Nursing School of Coimbra (ESEnfC) and funded by the Foundation for Science and Technology (FCT).

The outbreak of COVID-19 might produce dramatic psychological effects on individuals’ lives. In this study, we aimed to explore the elements that may reduce the negative effects on mental health of the quarantine period imposed by most governments during this worldwide crisis. We conducted an online survey to evaluate demographic, lifestyle and mental health variables in a sample of 1280 Portuguese individuals (79.8% females) with an average age of 37 years. We observed that factors related to living conditions, maintaining work either online or in the workplace, frequency of exercise and absence of previous psychological or physic disorders are protective features of psychological well-being (anxiety, depression, stress and obsessive-compulsive symptoms). Finally, the individuals previously receiving psychotherapeutic support exhibited better psychological indicators if they did not interrupt the process as a consequence of the outbreak. Our results indicate that the practice of physical exercise, reduced consumption of COVID-19 information and the implementation of remote mental healthcare measures might prevent larger impacts on mental health during the COVID-19 outbreak., This work was funded by the Foundation for Science and Technology (FCT), under the scope of the project 110_596697345 (Research 4 COVID) and partially funded by the FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by national funds, through the Foundation for Science and Technology (FCT), under the scope of the project UID/Multi/50026/2019. This manuscript has been developed under the scope of the project NORTE 01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER).

Background: Psychiatry gained ground as a science in the 19th century, in Portugal, and important laws were created in this context. Although nurses were care providers in various health institutions, it was also at this time that nursing was born as a profession. Objectives: To analyze the law presented; to explain its importance in the development of psychiatry and mental health in Portugal; to identify its contributions to the history of Portuguese psychiatric and mental health nursing. Methodology: Historical research, using as source the Law of 4 July 1889, Government Gazette No. 155 of 15 July 1889. Results: In Portugal, there was a need for the legislation and organization of care provision to the insane, creating structures suitable for this purpose. However, the legislative interventions planned were never implemented, and thus poor care was provided to the insane in Portugal until the end of the 19th century. Conclusion: This law was important for the development of mental health and psychiatry in Portugal because it was the first legal document issued in this domain., Contexto: A psiquiatria em Portugal ganhou relevo como ciência nos anos de oitocentos, sendo criada legislação importante nesse âmbito e, embora os enfermeiros fossem praticantes da assistência nas diversas instituições de saúde, foi igualmente nessa época que a enfermagem nasceu como profissão. Objetivos: Analisar a lei em apreço; indicar a sua importância no desenvolvimento da psiquiatria e da saúde mental em Portugal; identificar contributos para a história da enfermagem de saúde mental e psiquiátrica portuguesa. Metodologia: Investigação histórica, utilizando-se como fonte a Lei de 4 de julho de 1889, Diário do Governo n.º 155 de 15 de julho de 1889. Resultados: Pretendia-se que a assistência dos alienados em Portugal fosse legislada e organizada, criando- se estruturas próprias para esse efeito. Contudo, as intervenções previstas a nível legislativo nunca foram concretizadas e o país manteve défices na assistência dos alienados até ao final do século XIX. Conclusão: A lei analisada foi importante para o desenvolvimento da saúde mental e da psiquiatria portuguesa, visto ter sido o primeiro documento legal emanado nesse domínio., Contexto: La psiquiatría en Portugal se desarrolló como ciencia en el siglo XIX, se creando una importante legislación en esta área y, si bien los enfermeros eran practicantes de asistencia en las instituciones de salud, fue también en ese momento cuando nació la enfermería como profesión. Objetivos: Analizar la ley presentada; mostrar su importancia en el desarrollo de la psiquiatría y de la salud mental en Portugal; identificar contribuciones para la historia de la enfermería de salud mental y psiquiátrica portuguesa. Metodología: Investigación histórica, utilizándose como fuente la Ley del 4 de julio de 1889, Diário do Governo n.º 155 de 15 de julio de 1889. Resultados: Se pretendía legislar y organizar la asistencia de los enajenados en Portugal, mediante la creación de estructuras para tal fin. Sin embargo, las intervenciones previstas a nivel legislativo nunca se llevaron a cabo y el país mantuvo déficits en la asistencia a los enajenados hasta finales del siglo XIX. Conclusíon: La ley analizada fue importante para el desarrollo de la salud mental y la psiquiatría portuguesa, ya que fue el primer documento legal emitido en esta área., (undefined)

Dissertação de mestrado em Enfermagem da Pessoa em Situação Crítica, Os enfermeiros do serviço de urgência encontram-se na linha da frente na luta contra a COVID-19, estando diretamente expostos ao novo Coronavírus, pelo contacto e tratamento de indivíduos infetados. A velocidade com que se propagou a pandemia COVID-19 e o número de vítimas que fez e continua a fazer, desencadeou nos profissionais de enfermagem problemas psicológicos, de entre os quais se salienta a ansiedade, resultante da perda de controlo da situação, do risco de infetar outros, inclusivamente os familiares e, claro está, o medo da morte. Desenvolveu-se um estudo quantitativo descritivo-correlacional, tendo como objetivos avaliar o nível de ansiedade dos enfermeiros de um serviço de urgência, face ao novo Coronavírus; descrever a relação entre o nível de ansiedade e as variáveis sociodemográficas, a experiência profissional no serviço e o resultado positivo para teste à COVID-19, assim como, identificar fatores relacionados com o nível de ansiedade dos enfermeiros. Recorreu-se à aplicação de um questionário como instrumento de colheita de dados com base na Escala de Avaliação de Ansiedade de Hamilton que categoriza a ansiedade em níveis, nomeadamente: normal, ligeira, moderada ou severa. Os resultados revelam que o score médio de ansiedade dos enfermeiros é de 15,1 o que a categoriza como ligeira. Verificou-se que existe relação estatisticamente significativa entre a ansiedade e a variável sexo e filhos, sendo que as mulheres apresentam níveis de ansiedade superiores aos homens e 71,4% dos enfermeiros que não têm filhos apresentam níveis de ansiedade ligeira, moderada ou severa. O fator relacionado com o nível de ansiedade identificado foi o sexo. Perante a atual situação pandémica e eventuais repercussões a longo prazo na saúde psicológica dos enfermeiros do serviço de urgência, considera-se importante e fundamental a monitorização dos níveis de ansiedade dos enfermeiros, em estudos futuros, de forma a caracterizar o seu estado emocional e a rastrear problemas nesta classe profissional. Tornam-se imperativos programas de intervenção com foco na proteção emocional dos enfermeiros., Emergency department nurses are at the front line fighting against COVID-19, being directly exposed to the new Coronavirus, through the contact and treatment of infected individuals. The speed with which the COVID-19 pandemic spread and the number of victims it caused and continues to do, triggered psychological problems in nursing professionals, among which anxiety, resulting from the loss of control of the situation, the risk of infecting others, including family members and, of course, the fear of death. A quantitative descriptive-correlational study was developed, aiming to assess the level of anxiety of nurses in an emergency department, in view of the new Coronavirus; describe the relationship between the degrees of anxiety and the sociodemographic variables, the professional experience in the department and the positive result for testing the COVID-19, as well as identify the different factors related to the degrees of anxiety in nursing staff. A questionnaire was used as a data collection instrument based on the Hamilton Anxiety Assessment Scale, which categorizes anxiety into levels, namely: normal, mild, moderate or severe. The results reveal that the nurses average anxiety score is 15.1, which categorizes it as mild. It was found that there is a statistically significant relationship between anxiety and the variable gender and children, with women having levels of anxiety higher than men and 71.4% of nurses who do not have children have levels of mild, moderate or severe anxiety. The factor related to the level of anxiety identified was the gender. In view of the current pandemic situation and possible long-term repercussions on the psychological health of nurses in the emergency department, it is considered important and fundamental to monitor nurses anxiety degrees, in future studies, in order to characterize their emotional state and track problems in this professionals. Intervention programs with a focus on nurses emotional protection become imperative.

O ensaio faz o elogio a Diego Armando Maradona. Um atleta (futebolista) que encimou o humano nas suas mais diversas dimensões. Por um lado, a imanência na sua complexidade individual, psicológica, social e axiológica (o bem, o bom, o belo e o seus contrários); por outro, a transcendência da (na) imanência na medida em que eleva facetas e virtudes que o homem comum não consegue mas gostaria de atingir. Maradona acabou por projetar toda a dimensão mítica e lendária dos arquétipos dos heróis Gregos e Romanos, onde excelência e fragilidade (sua superação) convivem, numa (re) interpretação incessante., The essay praises Diego Armando Maradona. An athlete (footballer) who summed up the human in its most diverse dimensions. On the one hand, immanence in its individual, psychological, social and axiological complexity (the good, the good, the beautiful and its contraries); on the other hand, the transcendence of (na) immanence insofar as it raises facets and virtues that the common man cannot achieve but would like to achieve. Maradona ended up projecting the entire mythical and legendary dimension of the archetypes of Greek and Roman heroes, where excellence and fragility (their overcoming) coexist, in an unceasing (re) interpretation., El ensayo elogia a Diego Armando Maradona. Un deportista (futbolista) que resumió lo humano en sus más diversas dimensiones. Por un lado, la inmanencia en su complejidad individual, psicológica, social y axiológica (lo bueno, lo bueno, lo bello y sus contrarios); por otro lado, la trascendencia de la (na) inmanencia en la medida en que plantea facetas y virtudes que el hombre común no puede lograr pero quisiera lograr. Maradona acabó proyectando toda la dimensión mítica y legendaria de los arquetipos de los héroes griegos y romanos, donde conviven excelencia y fragilidad (su superación), en una (re) interpretación incesante., Este trabalho foi financiado por Fundos Nacionais através da FCT – Fundação para a Ciência e a Tecnologia no âmbito dos projetos do CIEC (Centro de Investigação em Estudos da Criança da Universidade do Minho) com as referências UIDB/00317/2020 e UIDP/00317/2020.

Dissertação de mestrado em Enfermagem da Pessoa em Situação Crítica, Juventude é sinónimo de longevidade. A morte de jovens assume uma conotação trágica e é vista como um dos maiores desafios enfrentados pelos profissionais de saúde. Nos serviços de urgência, além de salvarem vidas, os enfermeiros cuidam de jovens e famílias em morte iminente. Nestes contextos o paradigma assistencial implica que as intervenções terapêuticas sejam urgentes e emergentes e dirigidas para a cura, através da estabilização das funções orgânicas alteradas. No entanto, muitas vezes, os jovens que recorrem ao serviço de urgência têm prognóstico de limite de vida, para o qual não existe efetivamente nenhuma hipótese de recuperação, ou todas as intervenções falham. Os enfermeiros perante esta realidade são continuamente confrontados com vivências pessoais que influenciam a sua conduta, e a sua forma de cuidar. O presente estudo pretende compreender as vivências dos enfermeiros com a situação de morte de jovens/família em contexto de urgência/emergência. Para responder ao objetivo proposto desenvolveu-se um estudo exploratório, descritivo do tipo fenomenológico, cuja recolha de dados foi efetuada no serviço de um hospital da região norte de Portugal com recurso à entrevista semiestruturada. Os participantes do estudo são enfermeiros que cumpriam os critérios definidos tendo em conta as considerações éticas e operacionais intrínsecas à investigação, bem como o princípio da saturação de dados. Os dados obtidos permitiram identificar quatro áreas temáticas, i) experiências dos enfermeiros perante a morte de um jovem; ii) dificuldades sentidas pelos enfermeiros perante a morte de um jovem; iii) estratégias utilizadas pelos enfermeiros para enfrentar a morte de jovens e iv) informação complementar. Dentro de cada área temática foram ainda identificadas categorias e subcategorias, como, equipa orientada para a cura; acontecimento contranatura; vivência marcante; tomada de decisão; comunicação de más notícias; informação e cuidado à família; identificação das necessidades efetivas da família; envolvimento emocional/gestão de sentimentos; transição da situação para o contexto pessoal; discussão de situações vivenciados e partilha de emoções e sentimentos com colegas de equipa; apoio familiar; afastamento dos cuidados/fuga/distanciamento e necessidade de apoio psicológico à equipa/debriefing. Os resultados revelaram que os cuidados aos jovens em morte iminente e família têm impacte emocional nos enfermeiros, sendo um acontecimento que os marca para sempre. Para além da gestão emocional os participantes revelaram dificuldades que se prendem com a tomada de decisão, a comunicação de más notícias, a informação e cuidado à família, a identificação das necessidades efetivas da família, a gestão das emoções e a transição da situação para o contexto pessoal. As estratégias mais utilizadas pelos participantes para minimizar o impacte das perdas foram a discussão das situações vivenciadas e a partilha de emoções e sentimentos com colegas de equipa, o apoio familiar e o afastamento dos cuidados. Conclui-se que a implementação de programas de debriefing em equipa e o apoio emocional aos profissionais, que vivenciam o evento morte de jovens, poderiam contribuir para minimizar os danos causados pelo impacte desta experiência, no sentido de melhorar a qualidade de vida dos profissionais que trabalham num serviço de urgência e consequentemente, a qualidade dos cuidados., Youth is synonymous with longevity. The death of young people assumes a tragic connotation and is seen as one of the greatest challenges faced by health professionals. In emergency department, in addition to saving lives, nurses care for young people and families in imminent death. In these contexts, the care paradigm implies that therapeutic interventions are urgent and emergent and directed towards cure, through the stabilization of altered organic functions. However, many times, the young people who resort to the emergency service have a life-limiting prognosis, for which there is effectively no chance of recovery, or all interventions fail. Nurses, faced with this reality, are continuously confronted with personal experiences that influence their conduct and their way of providing care. This study aims to understand how nurses experience the situation of death of young people/family in an emergency context. To answer the proposed objective, an exploratory and descriptive phenomenological study was developed, which data were collected in the unit of a hospital in the northern region of Portugal, using semi-structured interview. The study participants were nurses who met the criteria defined, taking into account the ethical and operational considerations intrinsic to the research, as well as the principle of data saturation. The data obtained allowed us to identify four thematic areas, i) nurses’ experiences when facing the death of a young person; ii) difficulties experiences by nurses when facing the death of a young person; iii) strategies used by nurses to deal with the death of young people and iv) additional information. Within each thematic area, categories and subcategories were also identified, such as: cure-oriented team; unnatural event; remarkable experience; decision-making; communication of bad news; family information and care; identification of the family’s effective needs; emotional involvement/management of feelings; transition of the situation to the personal context; discussion of situations experienced and sharing of emotions and feelings with teammates; family support; withdrawal from care/escape/distancing and need for phycological support to the team/debriefing. The results revealed that the care provided to young people in imminent death and their families has an emotional impact on nurses, as it is an event that marks them forever. The results revealed that the care with imminent death of young people and their families impact the nurses emotionally, being an event that marks them forever. Besides the emotional management, the participants have shown difficulties regarding decision making, bad news communication, information and care towards the family, identify effective family needs, emotion management, and the situation's transition to the personal context. The main strategies used by the participants to minimize the impact of loss were discussing the experiences lived and sharing their feelings and emotions with their teammates, family support, and care withdrawal. In conclusion, the debriefing team programs' implementation and psychological support to professionals who experience situations of death of young people may contribute to minimizing the effects caused by these types of events, in order to improve the quality of life of these professionals and the quality of care.

Background:Spousal care is the most important source of informal care inold age.Nevertheless, despite the growing importance of this issue, the association betweenproviding spousal care inside the household and pain remains unexplored in Europe.Objective and Methods:This study aims to estimate the prevalence of pain reportedby spouse caregivers aged 65 plus that provide care inside the household and toinvestigate the association between providing spousal care and pain. Data from 17European countries that participated in wave 6 of the Surveyof Health, Aging andRetirement in Europe (SHARE) is used. The analyses are basedon 26,301 respondentsaged 65 years and older who provide informal care inside the household to theirspouse/partner exclusively (N=1,895) or do not provide any informal care (inside oroutside the household) (24,406). Descriptive statistics and multilevel logistic regressions(individual-level as level 1, and country as level 2) were performed.Results:Overall, spouse caregivers report pain more often (63.4%) than theirnon-caregiver‘s counterparts (50.3%). Important differences in the prevalence of painamong spouse caregivers were found between countries, withPortugal (80.3%), Spain(74.6%), France (73%), Italy (72.4%), and Slovenia (72.1) showing the highest prevalenceof pain, and Denmark (36%), Switzerland (41.5) and Sweden (42.3%), the lowest. Resultsfrom multilevel logistic regressions show that European individuals aged 65+who providespousal care have an increased likelihood of reporting pain(OR 1.30; CI=1.13–1.48).Conclusion:Our results suggest that in Europe, spouse caregivers aged 65+are atgreater risk of experiencing pain. Therefore, European policymakers should considerspouse caregivers as a health priority group, and take measures to ensure they receivecomprehensive health and socio-economic support, VS/2009/0562; Fundação Calouste Gulbenkian; PINFRA/22209/2016; SHARE-DEV3

Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a twostage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4rs7526628T/T genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4rs7526628T allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungicidal activity (p = 0.048). In addition, we observed that each copy of the MAPKAPK2rs12137965G allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2rs17013271T allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2rs12137965G allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (p = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (p = 0.00097). Finally, we also found that carriers of the protective MAPKAPK2rs17013271T allele had decreased numbers of CD27-IgM-IgD- B cells (p = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (p = 0.00018 and 0.00023). Altogether, these results suggest a role of the TNFSF4 and MAPKAPK2 genes in determining IA risk., Instituto de Salud Carlos III PI17/02276, ERA-NET PathoGenoMics PIM2010EPA-00756 0315900A, Collaborative Research Center/Transregio 124 FungiNet, Portuguese Foundation for Science and Technology PTDC/SAU-SER/29635/2017 PTDC/MED-GEN/28778/2017 CEECIND/03628/2017 CEECIND/04058/2018, European Union (EU) 847507, La Caixa Foundation ID 100010434, Portuguese Foundation for Science and Technology LCF/PR/HP17/52190003, PI20/01845, PI12/02688

Relatório de estágio de mestrado da Pessoa em Situação critica, No âmbito do Estágio do Mestrado em Enfermagem da Pessoa em Situação Crítica, da Escola Superior de Enfermagem da Universidade do Minho em consórcio com a Escola Superior de Enfermagem da Universidade de Trás-os-Montes e Alto Douro, decorrido num Serviço de urgência foi realizado o presente relatório. Este relatório para além de descrever e refletir sobre as atividades e competências desenvolvidas também descreve o projeto de intervenção desenvolvido no serviço ao longo do estágio, no âmbito da temática “O lugar da formação continua na atuação da equipa da sala de emergência nos cuidados à pessoa em situação critica”. A formação em contexto de urgência influencia direta e favoravelmente os níveis de desempenho dos enfermeiros perante emergências tais como peri-paragem/PCR. A continua e constante formação de qualidade diminui consideravelmente os riscos para o doente no sentido em que diminui o caos em que se pode tornar o serviço de urgência perante situações de life saving em que os profissionais de saúde concretamente os enfermeiros pelas mais variadas razões não estejam devidamente preparados para atuar em conformidade com a situação, por falta de formação complementar ou prática. A finalidade principal deste trabalho é detetar as lacunas existentes nas equipas alocadas à sala de emergência e trabalhar essas “falhas” com o intuito de melhorar a confiança e desempenho dos enfermeiros perante situações de emergência e assegurar a prestação de cuidados de alta qualidade, diminuindo assim o caos e a perda de controlo que se podem instalar devido à falta de formação/conhecimento de atuação. O plano de ação implementado passou pela aplicação de uma grelha de observação, direcionada aos aspetos que a mesma pretende observar objetivamente nos enfermeiros do serviço de urgência/emergência do Hospital em análise antes e após a ministração de formação de acordo com as guedlines. Após a análise dos resultados, o objetivo mediante os resultados obtidos e as ilações retiradas, foi organizar e ministrar uma formação com o intuito de melhorar os níveis de qualidade da prestação de cuidados de enfermagem ao doente crítico. Dos 6 casos abrangidos em contexto de sala de emergência cerca de 80% dos casos cumpriram com os itens observados na grelha. Quando observados os procedimentos realizados pelos enfermeiros, verifica-se que estes adaptam a sua prática clínica às suas aprendizagens e experiências pessoais, embora cumpram os protocolos instituídos. Conseguem seguir os algoritmos preconizados, mas gerem o cenário dentro das suas próprias experiências inclusive, com métodos de trabalho adequados às suas equipas. Constata-se assim que o facto de existirem equipas previamente formadas em suporte avançado de vida e, consequentemente na abordagem ao doente critico favorece os níveis de desempenho dos enfermeiros, melhorando e assegurando consideravelmente a segurança do doente critico., As part of the Internship of the Master's Degree in Nursing of the Critical Person, from the Higher School of Nursing at the University of Minho in consortium with the Higher School of Nursing at the University of Trás-os-Montes and Alto Douro, which took place in an emergency service, it was carried out this report. This report, in addition to describing and reflecting on the activities and skills developed, also describes the intervention project developed in the service throughout the internship, under the theme “The place of training continues in the performance of the emergency room team in caring for the person in critical situation ”. Training in an emergency context directly and favorably influences the performance levels of nurses in the face of emergencies such as peri-stop / CRP. The continuous and constant quality training reduces considerably the risks for the patient in the sense that it reduces the chaos in which the emergency service can become in the face of life saving situations in which health professionals, specifically nurses, for the most varied reasons are not properly prepared to act in accordance with the situation, due to lack of complementary or practical training. The main purpose of this work is to detect the gaps in the teams allocated to the emergency room and work on these “failures” in order to improve nurses' confidence and performance in emergency situations and ensure the provision of high quality care, thus reducing the chaos and loss of control that can be installed due to lack of training / knowledge of performance. The implemented action plan included the application of an observation grid, directed to the aspects that it intends to observe objectively in the nurses of the urgency / emergency service of the hospital under analysis before and after the training in accordance with the guedlines. After analyzing the results, the objective, based on the results obtained and the lessons learned, was to organize and provide training in order to improve the levels of quality in the provision of nursing care to critically ill patients. Of the 6 cases covered in the emergency room context, about 80% of the cases complied with the items observed in the grid. When observing the procedures performed by nurses, it appears that they adapt their clinical practice to their learning and personal experiences, although they comply with the established protocols. They manage to follow the recommended algorithms, but manage the scenario within their own experiences, including working methods appropriate to their teams. It can be seen that the fact that there are teams previously trained in advanced life support and, consequently in the approach to the critical patient, favors the performance levels of nurses, improving and ensuring considerably the safety of the critical patient.

We aim to evaluate the associations between digital health literacy (DHL) related to COVID-19 and online information-seeking behavior among university students. Methods: A total of 3.084 students (75.7% women), with an average age of 24.2 (SD = 7.5) participated in this cross-sectional study, most of whom (36.5%) were from social sciences and pursued a bachelor&rsquo, s degree (50.7%). Data on COVID-19-related DHL and online information-seeking behavior were collected using an online questionnaire. Logistic regression models were performed. Results: As the pandemic progressed, participants showed a lower chance of achieving a sufficient DHL (OR = 0.7, 95% CI = 0.6, 0.9). Using search engines more often (e.g., Google) (OR = 0.7, 95% CI = 0.5, 0.9), Wikipedia (OR = 0.7, 0.9) and social media (e.g., Facebook) (OR = 0.7, 0.9) decreased the likelihood of achieving sufficient DHL related to COVID-19. More frequent use of websites of public bodies (OR = 1.7, 95% CI = 1.1, 2.5) increased the odds of reporting sufficient DHL. Conclusion: DHL is associated with university students&rsquo, online information-seeking behavior in the time of COVID-19. From a community and public health perspective, programs aiming at improving DHL should be highlighted.

Objetivo: Avaliar o desenvolvimento psicomotor de crianças com baixo peso. Metodologia: Estudo de campo, descritivo, observacional, transversal e com abordagem quantitativa, realizado no período de abril a julho de 2017, no Instituto da Primeira Infância. Foi aprovado pelo parecer 2.007.070/2017, seguindo a Resolução 466/12. Foram avaliadas 34 crianças com a faixa etária de 4 a 6 anos, utilizando a Bateria Psicomotora de Vitor da Fonseca – adaptada. Os dados foram analisados pelo software Statistical Packcage for the Social Sciences versão 20.0. Resultados: Predomínio do gênero feminino, da faixa etária de 6 anos e da renda mensal de até 1 salário mínimo. Do total de participantes, observou-se que 20 (59,8%) apresentaram o perfil dispráxico, 12 (35,2%) o perfil normal e dois (5,9%) o perfil bom. Correlacionando os fatores psicomotores com o perfil observou-se que, com exceção da tonicidade, todos os outros seis fatores (equilíbrio, lateralidade, noção de corpo, estruturação espaçotemporal, praxia global e fina) obtiveram valores com a prevalência de pontuação 1 e 2, definindo um deficit psicomotor decorrente do baixo peso. Foi constatado também que 16 (57,1%) crianças, mesmo com a recuperação do estado nutricional, ainda apresentavam o perfil dispráxico. Conclusão: É possível, por meio de ações conjuntas de acompanhamento nutricional e intervenção da psicomotricidade, restabelecer o déficit psicomotor e favorecer uma intervenção direcionada para o desenvolvimento psicomotor da criança., Objective: To evaluate the psychomotor development of children with low weight. Methods: Field study, descriptive, observational, transversal and with quantitative approach, carried out from april to july 2017, in early childhood institute. It was approved by the 2.007.070/2017, following Resolution 466/12. Were evaluated 34 children aged 4 to 6 years, using the Psychomotor Battery in Vitor da Fonseca – adapted. The data were analyzed by software Statistical Packcage for the Social Sciences version 20.0. Results: Prevalence of the female gender, the age group of six years and the monthly income of up to one minimum wage. From the total of participants, it was observed that 20 (59,8%) presented the dyspraxic profile, 12 (35,2%) the normal profile and two (5,9%) the good profile. Correlating the psychomotor factors with the profile, it was observed that, with the exception of tonicity, all other six factors (balance, laterality, body notion, spatio-temporal structuring, global and fine praxis) obtained values with the prevalence of scores 1 and 2, defining a psychomotor deficit due to low weight. It was also found that 16 (57,1%) children, even with recovery of nutritional status, still presented the dyspraxic profile. Conclusions: It is possible through joint actions of nutritional monitoring and intervention of psychomotricity, reestablish the low weight and favor an intervention directed to the psychomotor development of the child., Este trabalho foi financiado por Fundos Nacionais através da FCT – Fundação para a Ciência e a Tecnologia no âmbito do projeto do CIEC (Centro de Investigação em Estudos da Criança da Universidade do Minho) com a referência UIDB/00317/2020.

CONTEXTO: O recovery é entendido como um processo subjetivo que pressupõe as dimensões clínica e pessoal. Os programas de intervenção comunitária na promoção do recovery devem basear-se em aspetos importantes como a qualidade de vida, suporte social e necessidades. OBJETIVOS: Avaliar o impacto de um programa de intervenção individualizado na qualidade de vida, suporte social e satisfação das necessidades, em pessoas com doença mental. MÉTODOS: Estudo quase-experimental com desenho antes-após de grupo único, com três momentos de avaliação com 16 sessões implementadas durante 4 meses. A amostra é constituída por 25 pessoas com doença mental selecionadas a partir da alta clínica de um hospital psiquiátrico da região Norte de Portugal. Utilizaram-se como instrumentos: Questionário de Avaliação Sociodemográfica e Clínica; Instrumento de Avaliação de Necessidades, construídos pelos investigadores; EQ-5D e; Escala de Satisfação com o Suporte Social. A Investigação foi aprovada pela Comissão de Ética da instituição onde foram recolhidos os dados. Foi utilizado o SPSS, versão 25.0, com recurso a medidas descritivas e testes de diferenças de médias não paramétricos - Friedman e de Wilcoxon - com um valor de significância de p, BACKGROUND: Recovery is understood as a subjective process that presupposes clinical and personal dimensions. Community intervention programs in the promotion of recovery should be based on importante aspects such as their needs, quality of life and social support. AIM: To evaluate the impact of an individualized intervention program on quality of life, social support and needs satisfaction in people with mental illness. METHODS: Quasi-experimental study with before-after design of single group, with three evaluation moments with 16 sessions implemented during 4 months. The sample consists of 25 people with mental illness selected from the high clinic of a psychiatric hospital in the Northern region of Portugal. The sociodemographic and clinical evaluation questionnaire, the Needs Assessment Instrument (NAI)., constructed by the researchers, the EQ-5D and the Social Support Satisfaction Scale were used as instruments. The investigation was approved by the Ethics Committee of the institution where the data were collected. SPSS, version 25.0 was used, using descriptive measures and tests of non-parametric mean differences - Friedman and Wilcoxon - with a significance level of p, CONTEXTO: La recuperación es un proceso subjetivo que presupone las dimensiones clínica y personal. Los programas de intervención comunitaria en la recuperación deben basarse en la calidad de vida, el apoyo social y las necesidades. OBJETIVOS: Evaluar el impacto de un programa de intervención individualizado en la calidad de vida, apoyo social y satisfacción de las necesidades, en personas con enfermedad mental. METODOLOGÍA: Estudio casi experimental con diseño antes-después de grupo único, con tres momentos de evaluación con 16 sesiones implementadas durante 4 meses. La muestra se compone de 25 personas con enfermedad mental seleccionados a partir del alta clínica de un hospital psiquiátrico en el norte de Portugal. Se utilizaron como instrumentos un cuestionario sociodemográfco y clínico, el Instrumento de Evaluación de Necesidades, construidos por los investigadores, el EQ-5D y la Escala de Satisfacción con el soporte social. La investigación fue aprobada por la Comisión de Ética de la institución donde se recogieron los datos. Se utilizó el SPSS, versión 25.0, con medidas descriptivas y pruebas de diferencias de promedios no paramétricos - Friedman y Wilcoxon - con un valor de signifcancia de p, Este artigo foi desenvolvido no âmbito do projeto (NORTE-01-0145-FEDER-023855), cofinanciado pelo Programa Operacional Regional do Norte (NORTE 2020), através do Portugal 2020 e do Fundo Europeu de Desenvolvimento Regional (FEDER)

Supplementary Material available at: https://www.mdpi.com/2076-2607/8/11/1678/s1, The novel coronavirus SARS-CoV-2 emerged from a zoonotic transmission in China towards the end of 2019, rapidly leading to a global pandemic on a scale not seen for a century. In order to cast fresh light on the spread of the virus and on the effectiveness of the containment measures adopted globally, we used 26,869 SARS-CoV-2 genomes to build a phylogeny with 20,247 mutation events and adopted a phylogeographic approach. We confirmed that the phylogeny pinpoints China as the origin of the pandemic with major founders worldwide, mainly during January 2020. However, a single specific East Asian founder underwent massive radiation in Europe and became the main actor of the subsequent spread worldwide during March 2020. This lineage accounts for the great majority of cases detected globally and even spread back to the source in East Asia. Despite an East Asian source, therefore, the global pandemic was mainly fueled by its expansion across and out of Europe. It seems likely that travel bans established throughout the world in the second half of March helped to decrease the number of intercontinental exchanges, particularly from mainland China, but were less effective between Europe and North America where exchanges in both directions are visible up to April, long after bans were imposed., This work was supported by strategic project ICVS/3B’s (UID/Multi/50025), financed by Fundação para a Ciência e Tecnologia/MCTES through national funds (PIDDAC) to Teresa Rito. Martin B. Richards and Maria Pala received support from a Leverhulme Doctoral Scholarship program. This work was partially supported by project NORTE-01-0145-FEDER000009) by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by “Contrato-Programa” UIDB/04050/2020 funded by Portuguese national funds through the Fundação para a Ciência e Tecnologia to Pedro A. Soares.

Obsessive-compulsive disorder (OCD) is characterized by cognitive regulation deficits. However, the current literature has focused on executive functioning and emotional response impairments in this disorder. Herein, we conducted a systematic review of studies assessing the behavioral, physiological, and neurobiological alterations in cognitive regulation in obsessive-compulsive patients using the PubMed database. Most of the studies included explored behavioral (distress, arousal, and frequency of intrusive thoughts) and neurobiological measures (brain activity and functional connectivity) using affective cognitive regulation paradigms. Our results pointed to the advantageous use of reappraisal and acceptance strategies in contrast to suppression to reduce distress and frequency of intrusive thoughts. Moreover, we observed alterations in frontoparietal network activity during cognitive regulation. Our conclusions are limited by the inclusion of underpowered studies with treated patients. Nonetheless, our findings support the OCD impairments in cognitive regulation of emotion and might help to improve current guidelines for cognitive therapy., This work has been funded by national funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020—and by the projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). S.F. was supported by a combined Ph.D. scholarship from the FCT and the company iCognitus4ALL—IT Solutions, Lda (grant number PD/BDE/127839/2016). The funding sources had not been involved in the study design, the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the article for publication.

Objetivo: identificar os conhecimentos e habilidades de enfermeiros para a prática baseada em evidência e suas práticas de pesquisa. Método: estudo realizado com 41 enfermeiros da Estratégia Saúde da Família, de um município no Sul do Brasil. A coleta de dados ocorreu por meio de um questionário, roteiro de questões auxiliares e grupo focal. Para análise utilizou-se estatística descritiva e análise de conteúdo temática. Resultados: identificou-se que há deficiência na formação acadêmica, para habilidades em pesquisa, bem como uma alta demanda de trabalho que dificulta a busca de evidências. Os enfermeiros consideraram a experiência clínica como o principal balizador de suas ações, além de que, carecem de conhecimentos e habilidades para produzir e utilizar estudos científicos. Conclusão: ainda é um desafio desenvolver a prática baseada em evidência, tencionando reflexões acerca do processo de formação profissional e da ênfase que a pesquisa tem na graduação e nos serviços de saúde.

Like severe influenza, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome (ARDS) has emerged as an important disease that predisposes patients to secondary pulmonary aspergillosis, with 35 cases of COVID-19 associated pulmonary aspergillosis (CAPA) published until June 2020. The release of danger-associated molecular patterns during severe COVID-19 results in both pulmonary epithelial damage and inflammatory disease, which are predisposing risk factors for pulmonary aspergillosis. Moreover, collateral effects of host recognition pathways required for the activation of antiviral immunity may, paradoxically, contribute to a highly permissive inflammatory environment that favors fungal pathogenesis. Diagnosis of CAPA remains challenging, mainly because bronchoalveolar lavage fluid galactomannan testing and culture, which represent the most sensitive diagnostic tests for aspergillosis in the ICU, are hindered by the fact that bronchoscopies are rarely performed in COVID-19 patients due to the risk of disease transmission. Similarly, autopsies are rarely performed, which may result in an underestimation of the prevalence of CAPA. Finally, the treatment of CAPA is complicated by drug–drug interactions associated with broad spectrum azoles, renal tropism and damage caused by SARS-CoV-2, which may challenge the use of liposomal amphotericin B, as well as the emergence of azole-resistance. This clinical reality creates an urgency for new antifungal drugs currently in advanced clinical development with more promising pharmacokinetic and pharmacodynamic profiles., AC was supported by the Fundação para a Ciência e a Tecnologia (FCT) (CEECIND/03628/2017, UIDB/50026/2020 and UIDP/50026/2020), and the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023). This research received no other external funding.

Este relatório tem por finalidade descrever as atividades e apresentar os principais resultados e indicadores relativos ao projeto "Doença mental: Intervenção Comunitária no Caminho do Recovery (InterComuniCaRe), cofinanciado pelo Programa Operacional Regional do Norte (NORTE 2020), através do Portugal 2020 e do Fundo Europeu de Desenvolvimento Regional (FEDER), cujo período de execução decorreu entre 15 de setembro de 2017 a 15 de março de 2019. Está organizado em quatro áreas: i) Dinâmica de Funcionamento; ii) Dimensão Investigativa; III) Dimensão Financeira - Desvios e; iv) Dimensão Reflexiva., Programa Operacional Regional do Norte (NORTE 2020), através do Portugal 2020 e do Fundo Europeu de Desenvolvimento Regional (FEDER)

Results from several studies show that only obese, unfit subjects, but not obese, fit subjects, are at higher mortality risk than are normal-weight fit subjects. The aim of the study was two-fold: (1) to examine the differences in C-reactive protein levels across different metabolic phenotypes (healthy and unhealthy) of weight status and (2) ascertain whether high levels of cardiorespiratory fitness (CRF) attenuate the association of C-reactive protein and metabolic phenotypes of weight status. This was a pooled study, which included data from three cross-sectional projects (1706 youth (921 girls) aged 12–18 years). We used a Shuttle run test to assess CRF. Adolescents were classified into six metabolic phenotypes (healthy and unhealthy) of weight status (non-overweight, overweight and obese), based on age- and sex-specific cutoff points for triglycerides, systolic blood pressure, HDL-cholesterol, glucose and body mass index. High-sensitivity assays were used to obtain the C-reactive protein as inflammatory biomarker. After adjustment for potential confounders (age, sex, pubertal stage and country), the analysis of covariance (ANCOVA) shows that C-reactive protein is directly associated with metabolic phenotypes of weight status. Subjects with obesity, regardless of their metabolic profile, had higher levels of C-reactive protein Z-score. In addition, (after adjustments for potential confounders) a two-way ANCOVA showed that high levels of CRF attenuated the associations of C-reactive protein levels in metabolic healthy non-overweight and in adolescents with obesity. In conclusion, higher CRF levels may attenuate the detrimental association between obesity and C-reactive protein independently of metabolic phenotype. Findings from this study are important for prevention, clinical practice on issues associated with adiposity and metabolic disorders., The Research Centre on Physical Activity Health and Leisure (CIAFEL) is supported by UID/DTP/00617/2013 (FCT). R.S. has a Discovery Early Career Research Award from the Australian Research Council (DE150101921). The FUPRECOL Study was carried out with the financial support of Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología “Francisco José de Caldas” COLCIENCIAS (Contract Nº 671-2014 Code 122265743978). The authors are grateful to the Bogota District Education Secretary for the data used in this study. The authors also thank the participating Bogota District students, teachers, schools and staff. This study was funded by the Department of Education (Grand number: CENEDUCA1/2019) of the Government of Navarra (Spain). A.G.-H. is a Miguel Servet Fellow (Instituto de Salud Carlos III—CP18/0150). R.R.-V. is funded in part by a Postdoctoral Fellowship Resolution ID 420/2019 of the Universidad Pública de Navarra.

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult., This research was funded by Prémios Santa Casa Neurociências—Prize Mantero Belard for Neurodegenerative Diseases Research (MB-28-2019); Portuguese Foundation for Science and Technology [Ph.D. fellowship to S.B.-A. (PD/BDE/135568/2018), B.M.-P. (SFRH/BD/120124/2016), A.M. (PDE/BDE/113598/2015), and D.S. (PD/BDE/135567/2018)]. This work was also funded by FEDER, through the Competitiveness Internationalization Operational Programme (POCI), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the projects POCI-01-0145-FEDER-007038; POCI-01-0145-FEDER-029751 and POCI-01-0145-FEDER-032619. This article has also been developed under the scope of the project NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER).

Prediction parameters of possible outcomes of canine leishmaniasis (CanL) therapy might help with therapeutic decisions and animal health care. Here, we aimed to develop a diagnostic method with predictive value by analyzing two groups of dogs with CanL, those that exhibited a decrease in parasite load upon antiparasitic treatment (group: responders) and those that maintained high parasite load despite the treatment (group: non-responders). The parameters analyzed were parasitic load determined by q-PCR, hemogram, serum biochemistry and immune system-related gene expression signature. A mathematical model was applied to the analysis of these parameters to predict how efficient their response to therapy would be. Responder dogs restored hematological and biochemical parameters to the reference values and exhibited a Th1 cell activation profile with a linear tendency to reach mild clinical alteration stages. Differently, non-responders developed a mixed Th1/Th2 response and exhibited markers of liver and kidney injury. Erythrocyte counts and serum phosphorus were identified as predictive markers of therapeutic response at an early period of assessment of CanL. The results presented in this study are highly encouraging and may represent a new paradigm for future assistance to clinicians to interfere precociously in the therapeutic approach, with a more precise definition in the patient’s prognosis., This work was funded by the Brazilian agencies Bahia Research Foundation—FAPESB (Grant nº PRONEM 498/2011-PNE 0002/2011 to S.M.B-M), National Council for Scientific and Technological Development —CNPq (PQ scholarship nº 307813/2018-5 to SMBM, and nº 303621/2015-0 to HG) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior —CAPES (PDSE scholarship nº 88881.189587/2018-01 to R.S.G; Finance Code 001 and PV scholarship nº 23066.033859/2018-73 to R.S.). This work was supported by grants from CESPU (TramTap-CESPU-2016, Chronic-TramTap_CESPU_2017 and TraTapMDMA-CESPU-2018), from the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), funded by FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI) and the Fundação para a Ciência e Tecnologia (FCT) (contract IF/00021/2014 to R.S.), Infect-Era (project INLEISH to R.S.) and Proyecto SNIP N◦ 292900 “Creación del Servicio de Laboratorio de Enfermedades Infecciosas y Parasitarias de Animales Domésticos de la Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas.Instituto de Investigación en Ganadería y Biotecnología-IGBI. Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas.

Sirtuins are emerging players in cancer biology and other age-related disorders, and their putative role in bladder cancer (BlCa) remains elusive. Further understanding of disease biology may allow for generation of more effective pathway-based biomarkers and targeted therapies. Herein, we aimed to illuminate the role of sirtuins’ family in BlCa and evaluate their potential as disease biomarkers and therapeutic targets. SIRT1-7 transcripts and protein levels were evaluated in a series of primary BlCa and normal bladder mucosa tissues. SIRT7 knockdown was performed through lentiviral transduction in MGHU3, 5637 and J82 cells and its functional role was assessed. SIRT1, 2, 4 and 5 expression levels were significantly lower in BlCa, whereas SIRT6 and 7 were overexpressed, and these results were corroborated by TCGA cohort analysis. SIRT7 transcript levels were significantly decreased in muscle-invasive vs. papillary BlCa. In vitro studies showed that SIRT7 downregulation promoted cells migration and invasion. Accordingly, increased EMT markers expression and decreased E-Cadherin (CDH1) was observed in those BlCa cells. Moreover, increased EZH2 expression and H3K27me3 deposition in E-Cadherin promoter was found in sh-SIRT7 cells. We demonstrated that sirtuins are globally deregulated in BlCa, and specifically SIRT7 downregulation is implicated in EMT, fostering BlCa invasiveness through EZH2-CDH1 axis., This research was supported by the Research Center of the Portuguese Oncology Institute of Porto (CI-IPOP–FBGEBC-27 and PI 74-CI-IPOP-19-2016), by Fundação para a Ciência e Tecnologia (FCT) (PhD fellowships SFRH/BD/112673/2015 to S.M.-R and SFRH/BD/92786/2013 to C.S.G.; IF/00601/2012 to B.M.C.), and by Fundo Europeu de Desenvolvimento Regional (FEDER) (post-doctoral fellowships IPO/ESTIMANORTE01-0145-FEDER-000027 to V.M.-G. and COMPETE/FEDER/FCT_CI-IPOP-BPD/UID/DTP/00776/2013 to I.G.).

Background: Colorectal cancer (CRC) surgery is associated with high rates of postoperative morbimortality. Sarcopenia has been identified as an independent predictor of these surgical outcomes. Methods: A sample of 272 patients who underwent CRC surgery between January 2005 and May 2010 at Braga Hospital, was selected. Sarcopenia was defined by the skeletal muscle mass index, measured by preoperative computed tomography (CT), at L3 level, using ImageJ&reg, software. Associations between sarcopenia and qualitative variables were analyzed by Chi-Square Test (&chi, 2) or Fisher&rsquo, s Exact Test and, for quantitative variables, by Mann-Whitney Test. A multivariate logistic regression was performed to assess if sarcopenia was an independent predictor of major morbidity. The overall and recurrence-free survivals were analyzed by Kaplan-Meier method and multivariate Cox regression was performed for recurrence-free survival. Results: The prevalence of sarcopenia was 19.1%. Sarcopenia was associated with male gender, no CRC family history and colon tumour (p &lt, 0.001, p = 0.029 and p = 0.017, respectively). The presence of sarcopenia was associated with postoperative morbidity Clavien&ndash, Dindo classification (p = 0.003), and sarcopenia was an independent predictor for major complications (grade &ge, III) (p = 0.003). Conclusions: The evaluation of sarcopenia in patients undergoing CRC surgical resection allows to predict a higher probability of major postoperative morbimortality.

Background: the presence of liver metastasis in colorectal cancer (CRC) remains one of the most significant prognostic factors. Objective: systematically review the results of studies evaluating the benefit of adding bevacizumab to a normal chemotherapy regime in the survival of patients with colorectal-cancer liver metastasis (CRLM). Search methods: Pubmed and Google Scholar databases were searched for eligible articles (from inception up to the 2 April 2019). Inclusion criteria: studies including patients with CRLM receiving anti-vascular endothelial growth factor (VEGF; bevacizumab) as treatment, overall survival as an outcome; regarding language restrictions, only articles in English were accepted. Main results: Eleven studies met the inclusion criteria. In 73% of these cases, chemotherapy with bevacizumab was an effective treatment modality for treating CRLM, and its administration significantly extended both overall survival (OS) and/or progression-free survival (PFS). Nevertheless, three articles showed no influence on survival rates of bevacizumab-associated chemotherapy. Author conclusions: It is necessary to standardize methodologies that aim to evaluate the impact of bevacizumab administration on the survival of patients with CRLM. Furthermore, follow-up time and the cause of a patient’s death should be recorded, specified, and cleared in order to better calculate the survival rate and provide a comparison between the produced literature., This research received no external funding.

This article belongs to the Special Issue Autophagy in Cancer., Autophagy is a highly conserved degradation mechanism that is essential for maintaining cellular homeostasis. In human disease, autophagy pathways are frequently deregulated and there is immense interest in targeting autophagy for therapeutic approaches. Accordingly, there is a need to determine autophagic activity in human tissues, an endeavor that is hampered by the fact that autophagy is characterized by the flux of substrates whereas histology informs only about amounts and localization of substrates and regulators at a single timepoint. Despite this challenging task, considerable progress in establishing markers of autophagy has been made in recent years. The importance of establishing clear-cut autophagy markers that can be used for tissue analysis cannot be underestimated. In this review, we attempt to summarize known techniques to quantify autophagy in human tissue and their drawbacks. Furthermore, we provide some recommendations that should be taken into consideration to improve the reliability and the interpretation of autophagy biomarkers in human tissue samples., This work was supported by grants from the Bernese Cancer League, “Stiftung für klinisch-experimentelle Tumorforschung”, and the Werner and Hedy Berger-Janser Foundation for Cancer Research (to M.H.); by Institute of Health Carlos III (ISCIII) and FEDER funds from the EU (PI14/01085 and PI17/00093) and supported by Miguel Servet contract by ISCIII and FSE funds (CPII16/00023) (to M.M.); from the Spanish Ministry of Science, Innovation and Universities (RTI2018-096748-B-100 to N.A.); from the University Professor Training Fellowship, Ministry of Science, Innovation and University, Government of Spain (FPU17/00026) (to P.C.O); from the ISCIII (PI16/00090 and PI19/01266) and the Andalusian Government (Consejería de Igualdad, Salud y Políticas Sociales, PI-0198-2016) for their financial support, and from the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd) founded by the ISCIII and co-financed by European Development Regional Fund (EDRF) “A way to achieve Europe” for their financial support (to J.M.), from Breakthrough Cancer Research, Ireland funding (to S.L.M); from the PI18/00442 grant integrated into the State Plan for R & D + I2013-2016 and funded by the ISCIII and the ERDF, a way to make Europe (to G.V.); from the Luxembourg National Research Fund (C18/BM/12670304/COMBATIC to B.J.); from the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, by the European Regional Development Fund (FEDER), through the Competitiveness Factors Operational Programme (COMPETE) (NORTE-01-0145-FEDER-000013) and from the projects POCI-01-0145-FEDER-028159 and POCI-01-0145-FEDER-030782 by FEDER, through the COMPETE (to P.L.); from National funds, through the Foundation for Science and Technology (FCT) (to P.L.); from ARRS—the Slovenian research agency, programme P1-0140: Proteolysis and its regulation (led by B. Turk) (to E.Ž.); from the Swiss Cancer Research (KFS-3360-02-2014) (to A.P, and M.P.T.) (KFS-3409-02-2014), and the Swiss National Science Foundation (31003A_173219) (to M.P.T.).

This article explains the state of Advance Directives (concerning living wills in case of inability to express one) in Portugal. It explores the causes of the low number of registered advance directives and proposes a standard form, one of the ways to increase citizen adherence.

Relatório de estágio de mestrado em Enfermagem da Pessoa em Situação Crítica, O presente relatório enquadra-se no âmbito do curso de Mestrado em Enfermagem à Pessoa em Situação Crítica, na Unidade Curricular de Estágio e Relatório Final ou Dissertação de Natureza Aplicada II. Cimentado por uma componente teórica, um dos objetivos deste relatório é descrever e refletir as atividades e intervenções desenvolvidas durante a evolução do estágio, analisando de forma crítico-reflexiva os saberes desenvolvidos na prática clínica bem como as competências adquiridas enquanto futura enfermeira especialista em enfermagem médico-cirúrgica. A realização do estágio numa Unidade de Cuidados Intensivos Polivalente (UCIP), bem como o desenvolvimento de um trabalho de projeto fundamentado pela metodologia de projeto suportaram o desenvolvimento destas competências. Neste enquadramento, o desenvolvimento de competências em contexto de estágio numa UCIP centrou-se nos domínios da prestação de cuidados, da formação, da gestão e da investigação, em concordância com as competências do enfermeiro especialista em enfermagem médico-cirúrgica. No domínio da prestação de cuidados à pessoa em situação crítica e família pudemos integrar competências técnicas, científicas, humanas e relacionais, sustentadas numa base ética. Os estudos de casos clínicos, as pesquisas de literatura científica e o debate com os profissionais do serviço, proporcionaram o desenvolvimento de estratégias face aos problemas encontrados. Sustentámos a sua organização e documentação através do Processo de Enfermagem. No domínio da formação estivemos envolvidas em diversas atividades que considerámos terem contribuído para a melhoria do desempenho profissional e para a uniformização dos cuidados. Paralelamente, permitiram uma atualização sistemática e o aperfeiçoamento dos conhecimentos e capacidades, imposta pelos avanços constantes da ciência e da tecnologia. No domínio da gestão, a utilização eficiente dos recursos existentes, com o fim de alcançar a máxima qualidade com o menor consumo de recursos, foi primordial na prestação de cuidados. Das atividades que desenvolvemos neste domínio destacamos a colaboração na gestão dos recursos humanos e materiais, gestão do risco clínico e, perante situações complexas, a aplicação dos feixes de intervenção da prevenção da infeção. No domínio da investigação, o ambiente criado numa Unidade de Cuidados Intensivos (UCI) aliado ao elevado desenvolvimento tecnológico em que as ações são sustentadas nos seus princípios põe em tese a prática do cuidado humano e, portanto, da temática da humanização dos cuidados. Esta, é uma situação complexa, vivenciada pelos enfermeiros da UCIP onde estagiámos, que expressaram sentir uma necessidade de transformação no sentido da melhoria dos cuidados de enfermagem que prestam. Assim, tivemos como objetivo: desenvolver uma Norma de Orientação Clínica (NOC) centrada na humanização de cuidados numa Unidade de Cuidados Intensivos, assente na metodologia de projeto. Pretendemos com esta NOC sensibilizar os enfermeiros para uma prática de cuidados centrados nas necessidades da pessoa em situação crítica e sua família e, deste modo, permitir uma postura ativa de forma a prestar cuidados mais humanizados, holísticos e eticamente sensíveis a fim de promover a saúde e o bem-estar da pessoa em situação crítica e família, tendo em conta as suas reais e potenciais necessidades. A elaboração deste relatório permitiu-nos evidenciar, analisar e refletir as aprendizagens adquiridas através da exposição das atividades realizadas para a consecução dos objetivos previamente traçados. Concluído este percurso, considerámos que foram desenvolvidas as competências do enfermeiro especialista e acreditámos, no futuro, sermos capazes de prestar cuidados especializados na área de enfermagem médico-cirúrgica, assente numa prática humanizadora, refletida e baseada na evidência científica., This report falls within the scope of the Master´s Degree in Nursing for People in Critical Situation, in the Internship Curricular Unit and Final Report or Dissertation of an Applied Nature II. Cemented by theorical component, one of the goals of this report is to describe and reflect about the activities and interventions developed during the evolution of the Internship Curricular Unit, analysing in a critical-reflexive way the knowledge developed in the clinical practice as well as the skills acquired as future specialist nurse in medical-surgical nursing. The accomplishment if the internship in a Multipurpose Intensive Care Unit (MICU), as well as the development of a project based on the Project Methodology, supported the development of these skills. In this context, the development of skills in the context of an internship at the MICU focused on the domains of care, training, management and research, in accordance with the skills of the specialist nurse in medical-surgical nursing. In the sphere of providing care to people in critical situations and family, we were able to integrate technical, scientific, human and relational skills, supported on an ethical basis. Clinical cases studies, the research of scientific literature and debate with the professionals from the department, provided the development of strategies for the problems found. We supported its organisation and documentation through the Nursing Process. In the area of training, we have been involved in several activities, which we considered that have contributed to the improvement of professional performance and the standardization of care. Parallelly, they allowed a systematic update and improvement of knowledge and skills, imposed by constant advances in science and technology. In the management field, the efficient use of the existing resources, in order to achieve maximum quality with the lowest consumption of resources, was primordial in the provision of care. From the all activities developed in this domain, we highlight the collaboration in the management of human and material resources, clinical risk management and, face to complex situations, the application of infection prevention intervention bundles. In the domain of research, the environment created in an Intensive Care Unit (ICU) combined with the high technology development in which the actions are based on its principles, underlines the practice of human care and therefore the theme of humanisation of care. This is a complex situation, experienced by ICU professionals, who expressed to feel a need for transformation in order to improve the care they provide. Thus, we had as goal: develop a Clinical Guidance Standard (CGS) focused on the humanisation of care in an Intensive Care Unit, according to the project work methodology, based on the assumptions of the AGREE II Instrument. With that, we intend to sensitise nurses to a care practice, focused on the needs of the critical person and their family and, therefore, allow an active posture in order to provide more humanised, holistic and ethically sensitive care, to promote, autonomously and independently, the health and well-being of the person in critical situation condition and their family, taking in account their real and potential needs. The elaboration of this document allowed us to emphasise, analyse and reflect the knowledge acquired through the exposure of the activities carried out to achieve the objectives previously set. We believe that the skills of the specialist nurse were developed, and we consider, in the future, to be able to provide specialised care in the medical-surgical nursing area, based on a humanising and reflected practice and based on scientific evidence.

A selection of new chromeno[2,3-b]pyridines was prepared from chromenylacrylonitriles and N-substituted piperazines, using a novel and efficient synthetic procedure. The compounds were tested for their anticancer activity using breast cancer cell lines MCF-7, Hs578t and MDA-MB-231 and the non-neoplastic cell line MCF-10A for toxicity evaluation. In general, compounds showed higher activity towards the luminal breast cancer subtype (MCF-7), competitive with the reference compound Doxorubicin. The in vivo toxicity assay using C. elegans demonstrated a safe profile for the most active compounds. Chromene 3f revealed a promising drug profile, inhibiting cell growth and proliferation, inducing cell cycle arrest in G /M phase, apoptosis and microtubule destabilization. The new compounds presented exciting bioactive features and may be used as lead compounds in cancer related drug discovery. 2, We acknowledge the financial support from University of Minho, Fundacao para a Ciencia e a Tecnologia (FCT) and FEDERCOMPETE for financial support through Centro de Quimica (UID/QUI/00686/2013 and UID/QUI/0686/2016), for the PhD grant awarded to Olivia Pontes (SFRH/BD/128850/2017) Research grant from Liga Portuguesa Contra o Cancro to Sofia Oliveira-Pinto. The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network (RNRMN) and was purchased within the framework of the National Program for Scientific Reequipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT. This work was also developed under the project NORTE-01-0145-FEDER-000013, by the Northern Portugal Regional Operational Program (NORTE 2020), through the European Regional Development Fund (FEDER) and the Competitiveness Factors Operational Program (COMPETE) and by National funds, through the Foundation for Science and Technology (ref. POCI-01-0145-FEDER-007038).

The discovery of glioblastoma stem cells (GSCs) in the 2000s revolutionized the cancer research field, raising new questions regarding the putative cell(s) of origin of this tumor type, and partly explaining the highly heterogeneous nature of glioblastoma (GBM). Increasing evidence has suggested that GSCs play critical roles in tumor initiation, progression, and resistance to conventional therapies. The remarkable oncogenic features of GSCs have generated significant interest in better defining and characterizing these cells and determining novel pathways driving GBM that could constitute attractive key therapeutic targets. While exciting breakthroughs have been achieved in the field, the characterization of GSCs is a challenge and the cell of origin of GBM remains controversial. For example, the use of several cell-surface molecular markers to identify and isolate GSCs has been a challenge. It is now widely accepted that none of these markers is, per se, sufficiently robust to distinguish GSCs from normal stem cells. Finding new strategies that are able to more efficiently and specifically target these niches could also prove invaluable against this devastating and therapy-insensitive tumor. In this review paper, we summarize the most relevant findings and discuss emerging concepts and open questions in the field of GSCs, some of which are, to some extent, pertinent to other cancer stem cells., J.V.C., C.S.G., and B.M.C. were supported by funds from the project NORTE-01-0145-FEDER-000013,supported by the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal Partnership Agreement, through the European Regional Development Fund (FEDER), and by National funds,through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020.

The recent global pandemic of COVID-19 has predisposed a relatively high number of patients to acute respiratory distress syndrome (ARDS), which carries a risk of developing super-infections. Candida species are major constituents of the human mycobiome and the main cause of invasive fungal infections, with a high mortality rate. Invasive yeast infections (IYIs) are increasingly recognized as s complication of severe COVID-19. Despite the marked immune dysregulation in COVID-19, no prominent defects have been reported in immune cells that are critically required for immunity to Candida. This suggests that relevant clinical factors, including prolonged ICU stays, central venous catheters, and broad-spectrum antibiotic use, may be key factors causing COVID-19 patients to develop IYIs. Although data on the comparative performance of diagnostic tools are often lacking in COVID-19 patients, a combination of serological and molecular techniques may present a promising option for the identification of IYIs. Clinical awareness and screening are needed, as IYIs are difficult to diagnose, particularly in the setting of severe COVID-19. Echinocandins and azoles are the primary antifungal used to treat IYIs, yet the therapeutic failures exerted by multidrug-resistant Candida spp. such as C. auris and C. glabrata call for the development of new antifungal drugs with novel mechanisms of action., M.H. received research funding by Gilead and Pfizer. D.S.P. receives research support and/or serves on advisory boards for Amplyx, Cidara, Scynexis, N8 Medical, Merck, Regeneron, and Pfizer. He also has a patent covering the detection of fungal species and drug resistance, as well as a pending patent on COVID-19 detection licensed to T2 Biosystems. A.C. was supported by the Fundação para a Ciência e a Tecnologia (FCT) (CEECIND/03628/2017 and PTDC/MED-GEN/28778/2017). Additional support was provided by FCT (UIDB/50026/2020 and UIDP/50026/2020), the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023), the European Union’s Horizon 2020 research and innovation program under grant agreement no. 847507, and the “la Caixa” Foundation (ID 100010434) and FCT under the agreement LCF/PR/HP17/52190003.

Prática Baseada em Evidências é uma abordagem que tem apresentado notoriedade para melhorar a efetividade clínica e apoiar o profissional de saúde nas suas condutas, utilizando três elementos: evidências científicas, a experiência clínica e as preferências do paciente. O objetivo do estudo é conhecer como se desenvolve a Prática Baseada em Evidências na Atenção Primária à Saúde, especificamente, na Estratégia Saúde da Família, bem como propor a inclusão do elemento “análise sociocultural” para a tomada de decisão. Estudo qualitativo, precedido da realização de dois grupos focais, com a participação de 14 profissionais de saúde. A técnica de análise de conteúdo temática foi utilizada para avaliação, tratamento e interpretação das informações. Os profissionais da Estratégia Saúde da Família têm dificuldade para desenvolver uma prática em saúde voltada a evidências científicas, apontando carência de conhecimentos e habilidades para a pesquisa e elevada carga de trabalho. Ademais, os resultados indicam que a Prática Baseada em Evidências deve ser diferenciada segundo a realidade dos territórios de atuação das equipes. Cabe aos profissionais de saúde identificar e valorar as características socioculturais da comunidade para uma Prática Baseada em Evidências mais sensível às necessidades de saúde de sua população adscrita., Evidence-Based Practice is an approach that has been renowned for improving clinical effectiveness and supporting health professional in their attitudes, by using three elements: scientific evidence, clinical experience and patients’ preferences. This study aimed at understanding how Evidence-Based Practice in Primary Health Care is developed, specifically, referring to Family Health Strategy, as well as proposing the inclusion of the "socio-cultural analysis" element for decision making. It was a qualitative study, preceded by two focus groups, having the participation of 14 health professionals. The thematic content analysis technique was used to evaluate, handle and understand information. Family Health Strategy professionals have difficulties in developing health practice focused on scientific evidence, showing their lack of knowledge and skills for research and also heavy workload. Moreover, results showed that Evidence-Based Practice should be differentiated according to the reality of the places where health professional teams work. It is the responsibility of health professionals to identify and to evaluate the sociocultural characteristics of the community for an Evidence-Based Practice that is more sensitive to the health needs of the population involved, CAPES -Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(undefined)

Background and aim: This study aimed to: i) examine the differences in insulin resistance (IR) across adiposity levels; and ii) ascertain whether high levels of adiponectin attenuate the detrimental association of adiposity with IR in adolescents.Methods and results: A total of 529 adolescents aged 12-18 years participated in this cross-sectional study (267 girls). Anthropometry and body adiposity parameters [body mass index (BMI), sum of skinfolds, body fat percentage (BF %) by bio-impedance analysis and waist circumference (WC)], were measured according to standardized procedures and categorized into age- and sex-specific quartiles. Socioeconomic status, pubertal stage and lifestyle determinants (Mediterranean diet adherence and cardiorespiratory fitness) were gathered and used as confounders. Serum adiponectin and IR (homeostasis model assessment of insulin resistance [HOMA-IR] estimated from fasting serum insulin and glucose were assessed. Analysis of covariance (ANCOVA) showed that HOMA-IR increased in a linear fashion throughout the quartiles of all adiposity measures (p < 0.001 for all), independently of age, sex, pubertal stage, socioeconomic status, adherence to the Mediterranean diet and cardiorespiratory fitness. Two-way ANCOVA showed that adolescents in the higher quartile of adiposity for BF%, BMI, WC and skinfolds sum (Q4) presented the highest adiponectin levels, and had 0.77 Standard Deviation (SD), 0.8 SD, 0.85 SD and 0.8 SD lower HOMA-IR, respectively (p < 0.01) than their low adiponectin group counterparts, after adjustments for potential confounders.Conclusion: Higher adiponectin levels may attenuate the detrimental association between adiposity and IR, particularly in subjects with higher adiposity. (C) 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University., The Research Centre on Physical Activity Health and Leisure (CIAFEL), Portugal is supported by UID/DTP/00617/2019 (FCT, Portugal). (FCT). R. S is supported by Portuguese Foundation for Science and Technology, Portugal: CEE-CIND/01069/2017 JM-was supported by grants: FCT: SFRH/BSAB/142983/2018 and UID/DTP/00617/2019 as well as Programa de Bolsas Santander Universidades 2018.Support Foundation of Sao Paulo Research - FAPESP, Brazil (2017/07372-1; 2015/14309-9; 2013/08522-6; 2011/50414-0; 2011/50356-0; 2008/53069-0, Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP), Brazil, National Council for Scientific and Technological Development - CNPq, Brazil (301322/2017-1) and Coordination of Higher Education Personnel Training - CAPES, Brazil.

Dissertação de mestrado em Enfermagem da Pessoa em Situação Crítica, O internamento numa Unidade de Cuidados Intensivos (UCI) é uma situação inesperada que envolve não só a pessoa em situação crítica, mas toda a família, despoletando sentimentos de angústia, incerteza, sofrimento e stress, provocando alterações drásticas nas rotinas diárias da família. Assim, é primordial que a família constitua um foco de atenção dos enfermeiros tão importante como o cuidar da Pessoa em Situação Crítica (PSC). Cuidar da PSC é um desafio, mas cuidar da sua família torna-se um desafio ainda maior. Mas, para ajudar a vivenciar todo este processo de saúde/doença de uma forma mais saudável é necessário que o enfermeiro conheça quais as principais necessidades sentidas pela família. E é na primeira visita à UCI que essas necessidades se tornam mais previsíveis. Por isso, é da competência do enfermeiro realizar um acolhimento adequado à família de forma a diminuir a ansiedade e gerar confiança e tranquilidade. Neste sentido foi desenvolvido um estudo quantitativo, de carater exploratório, descritivo-correlacional e transversal, delineando como objetivos identificar e descrever as principais necessidades sentidas pelos familiares da PSC e analisar a correlação entre as diferentes dimensões e as respetivas variáveis. A amostra não probabilística por conveniência e correlacional foi constituída por 88 familiares de referência de doentes internados em três UCI num hospital do norte de Portugal. Para a recolha de dados foi utilizado o Inventário das Necessidades da Família na Unidade de Cuidados Intensivos (INFUCI), adaptada para a população portuguesa por Sara Campos em 2014. Os resultados evidenciaram que os familiares atribuíram uma maior importância à necessidade segurança (M=3,87; DP=0,33), seguida de informação (M=3,58; DP=0,36), proximidade (M=3,49; DP=0,33), suporte (M=3,08; DP=0,37) e, por último, as necessidades relacionadas com o conforto (M=2,98; DP=0,44). Constatou-se que a nível de correlações entre as diferentes dimensões são estatisticamente positivas (variando com um coeficiente de Pearson entre 0,337 e 0,643), à exceção da dimensão conforto/segurança que não apresenta significado estatístico (r=0,205). Quanto às correlações entre as dimensões e os dados sociodemográficos, verificou-se que a única variável com significado estatístico é o sexo do participante, em que o sexo feminino atribuiu maior importância à dimensão informação (M=3,65), suporte (M=3,165) e conforto (M=3,07), comparativamente com o sexo masculino., The hospitalization in an Intensive Care Unit (ICU) is an unexpected situation that involves not only the person in a critical situation, but the whole family, triggering feelings of anguish, uncertainty, suffering and stress, causing drastic changes in the daily routines of the family. In that regard, family is as important as the care of the Person in Critical Situation (PCS). Taking care of the PCS is a challenge but taking care of her family becomes an even bigger challenge. However, to help to experience this whole health/disease process in a healthier way, it is necessary that nurses know the main needs felt by the family. And it is on the first visit to the ICU that these needs become more predictable. Therefore, it’s up to the nurses to provide an adequate welcome to the family in order to reduce anxiety and generate confidence and tranquility. In this sense, a prospective, descriptive, exploratory and transversal study, with a quantitative approach was developed, aiming to identify and describe the main needs felt by the family members of the PCS and to analyze the correlation between the different dimensions and their variables. The non-probabilistic sample for convenience and correlation was composed of 88 relatives of patients hospitalized in three IUC in a hospital in northern Portugal. For data collection, the Family Needs Inventory was used in the Intensive Care Unit (INFUCI), adapted for the Portuguese population by Sara Campos in 2014. The results showed that family members placed greater importance on the need for safety (M=3.87; DP=0.33), followed by information (M=3.58; DP=0.36), proximity (M=3.49; DP=0.33), support (M=3.08; DP=0.37) and, finally, comfort-related needs (M=2.98; DP=0.44). It was found that the level of correlations between the different dimensions are statistically positive (varying with a Pearson coefficient between 0.337 and 0.643), except for the comfort/safety dimension that has no statistical significance (r=0.205). Regarding the correlations between dimensions and sociodemographic data, it was found that the only variable with statistical significance is the gender of the participant, in which the female gender attributed greater importance to the information dimension (M=3.65), support (M=3.165) and comfort (M=3.07), compared to males.