RCAAP Repository

Coastal flooding (CF), enhanced by climate change, is one of the most significant impacts of sea level rise (SLR). Bissau city, home to ~25% of Guinea-Bissau population is already affected by CF due to tides and storms. It is anticipated that the situation will deteriorate in coming decades with the expected scenarios of SLR. This article evaluated the vulnerability to coastal flooding of Bissau, using the single-value model, which considers two variables: inundation value and a topographic surface. The inundation value, here referred as total water level (TWL) was estimated by the sum of three vertical components: astronomical tide (AT), storm surge (SS) and the SLR estimation for the considered scenario. Thus, the inundation extension was quantified and mapped using a TWL estimated for the year 2100, and a high-precision global Digital Elevation Model (DEM – TanDEM-X) of the Bissau region. The results indicate that the land potentially to be flooded corresponds to 29.3% of the study area (94.9 km²). The Southwest zone of Bissau presents greater exposure to flooding, due to its low altitude. Also, the disorderly anthropogenic occupation of flooded lands, makes these areas more vulnerable in a climate change scenario.

Background: Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells. Methods: We developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders. Results: We observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC. Conclusions: This study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation.

O presente relatório diz respeito a um trabalho de final de mestrado na modalidade de relatório de estágio, de natureza descritiva, técnica e científica, elaborado na sequência de um primeiro estágio realizado no Centro de Estudos de Teatro, da Faculdade de Letras da Universidade de Lisboa. O estágio permitiu o aprofundamento de competências profissionais sobre a temática dos arquivos pessoais, tendo por base o arquivo pessoal de Osório Mateus, relevante para a preservação da memória do teatro em Portugal no século XX. Tem como principais objectivos gerais: compreender o universo, nacional e internacional, dos arquivos pessoais e contribuir para a preservação da memória do teatro em Portugal. Como objectivos específicos: efectuar o estudo biográfico de Osório Mateus; identificar, organizar e representar a informação do arquivo pessoal; promover o acesso democrático e universal à informação, através da web; apreender o lugar de Osório Mateus no teatro em Portugal no século XX. O arquivo pessoal foi doado à Faculdade de Letras da Universidade de Lisboa por Osório Mateus, professor da Faculdade de Letras da Universidade de Lisboa. É um conjunto constituído, na sua maioria, por programas de espectáculos e folhas de sala, cotados manualmente por quem recolheu a colecção em casa do doador, apresentando, uma lógica de organização. Seguiu-se o paradigma positivista, uma vez que se partiu de uma pesquisa bibliográfica, na qual se procurou analisar os estudos já realizados em arquivos de teatro. De seguida, identificaram-se as tipologias documentais, na sua maioria, programas de espectáculos e folhas de sala, tendo-se procedido à sua descrição e representação na base de dados da Biblioteca da Faculdade de Letras da Universidade de Lisboa, segundo a norma ISBD (versão consolidada), havendo a adaptação de alguns campos do template para a descrição dos objectos. Passando a integrar o sistema de informação e pesquisa da referida Biblioteca, a informação encontra-se organizada, representada e disponível para consulta dos utilizadores.

O trabalho desenvolvido no âmbito desta dissertação pretende desvendar como a vontade de um grupo de anónimos, sedentos das artes dramáticas, conseguiu erigir um espaço - o do Teatro Aveirense - que conta com mais de 125 anos de vida. As suas necessidades e motivações, as alegrias e tristezas, as vicissitudes dos tempos e os problemas inerentes a tão grandiosa obra numa cidade de província. Paralelamente, são apresentadas as companhias e peças que se exibiram nos palcos da cidade, tomando em consideração o seu registo cronológico. Dá-se especial destaque às companhias amadoras devido à importância que tiveram na formação de públicos e mentalidades, bem como no seu papel preponderante para a História do Teatro em Portugal.

This thesis aims to contribute to a better understanding of the history of biology in Portugal. Genetics in Portugal emerged in the 1930s. Why not before and how this took place were the two questions I proposed to answer in the fist part of this thesis. My approach focuses on the dynamics between different biological communities and on the influence other “national traditions” in biology had on a periphery such as Portugal. A historical survey of the first decades of the twentieth century regarding the extant sources on Mendelism is provided and the influence of the French tradition in biology is debated. In the second part, following the scientific life of the leading Portuguese geneticist J. A. Serra (from 1936 until 1952), I analyse the emergence of genetics in the Faculty of Sciences of the University of Coimbra, discussing the influence of German genetics during World War II. Here I add a further dimension by looking into the relation between science and politics, as a reciprocal one. Two main conclusions: 1) the emergence of genetics in Portugal during the 1930s played a crucial role on the migration of experimental practices among different biological communities; and 2) the consolidation of genetics in the university context of Coimbra was shaped and occasionally benefited from the political agenda of the New State.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow shear stress. HGPS-iPSC SMCs cultured under arterial flow conditions detach from the chip after a few days of culture; this process is mediated by the upregulation of metalloprotease 13 (MMP13). Importantly, double-mutant LmnaG609G/G609GMmp13-/- mice or LmnaG609G/G609GMmp13+/+ mice treated with a MMP inhibitor show lower SMC loss in the aortic arch than controls. MMP13 upregulation appears to be mediated, at least in part, by the upregulation of glycocalyx. Our HGPS-SMCs chip represents a platform for developing treatments for HGPS individuals that may complement previous pre-clinical and clinical treatments.

Mammalian cells display a broad spectrum of phenotypes, morphologies, and functional niches within biological systems. Our understanding of mechanisms at the individual cellular level, and how cells function in concert to form tissues, organs and systems, has been greatly facilitated by centuries of extensive work to classify and characterize cell types. Classic histological approaches are now complemented with advanced single-cell sequencing and spatial transcriptomics for cell identity studies. Emerging data suggests that additional levels of information should be considered, including the subcellular spatial distribution of molecules such as RNA and protein, when classifying cells. In this Perspective piece we describe the importance of integrating cell transcriptional state with tissue and subcellular spatial and temporal information for thorough characterization of cell type and state. We refer to recent studies making use of single cell RNA-seq and/or image-based cell characterization, which highlight a need for such in-depth characterization of cell populations. We also describe the advances required in experimental, imaging and analytical methods to address these questions. This Perspective concludes by framing this argument in the context of projects such as the Human Cell Atlas, and related fields of cancer research and developmental biology.

The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.

Kyotorphin (KTP, l-tyrosyl-l-arginine) is an endogenous dipeptide initially described to have analgesic properties. Recently, KTP was suggested to be an endogenous neuroprotective agent, namely for Alzheimer's disease (AD). In fact, KTP levels were shown to be decreased in the cerebrospinal fluid of patients with AD, and recent data showed that intracerebroventricular (i.c.v.) injection of KTP ameliorates memory impairments in a sporadic rat model of AD. However, this administration route is far from being a suitable therapeutic strategy. Here, we evaluated if the blood-brain permeant KTP-derivative, KTP-NH2, when systemically administered, would be effective in preventing memory deficits in a sporadic AD animal model and if so, which would be the synaptic correlates of that action. The sporadic AD model was induced in male Wistar rats through i.c.v. injection of amyloid β peptide (Aβ). Animals were treated for 20 days with KTP-NH2 (32.3 mg/kg, intraperitoneally (i.p.), starting at day 3 after Aβ administration) before memory testing (Novel object recognition (NOR) and Y-maze (YM) tests). Animals were then sacrificed, and markers for gliosis were assessed by immunohistochemistry and Western blot analysis. Synaptic correlates were assessed by evaluating theta-burst induced long term potentiation (LTP) of field excitatory synaptic potentials (fEPSPs) recorded from hippocampal slices and cortical spine density analysis. In the absence of KTP-NH2 treatment, Aβ-injected rats had clear memory deficits, as assessed through NOR or YM tests. Importantly, these memory deficits were absent in Aβ-injected rats that had been treated with KTP-NH2, which scored in memory tests as control (sham i.c.v. injected) rats. No signs of gliosis could be detected at the end of the treatment in any group of animals. LTP magnitude was significantly impaired in hippocampal slices that had been incubated with Aβ oligomers (200 nM) in the absence of KTP-NH2. Co-incubation with KTP-NH2 (50 nM) rescued LTP toward control values. Similarly, Aβ caused a significant decrease in spine density in cortical neuronal cultures, and this was prevented by co-incubation with KTP-NH2 (50 nM). In conclusion, the present data demonstrate that i.p. KTP-NH2 treatment counteracts Aβ-induced memory impairments in an AD sporadic model, possibly through the rescuing of synaptic plasticity mechanisms.

People living with Parkinson's disease (PwP) experience a wide range of motor and non-motor symptoms associated with increasing complexity of care delivery. A multispecialty approach has been presented as an intuitive solution for tailored and comprehensive care delivery. Nevertheless, past trials of both multidisciplinary or interdisciplinary care models in PD suggested no measurable change to a small benefit in quality of life (QoL) and failed to show economic sustainability. We propose a home-based community-centred integrated care (iCARE-PD) for PwP as a pragmatic solution to harness the potential of existing care resources using an integrated care strategy, enable self-management support and implement technology-enabled care. The iCARE-PD model is based on Freeman's concept of continuity of care and the expanded Chronic Care Model for organization of care strategies. A home-based community-centred integrated care has immediate implications for clinical practice, with potential benefits in rural areas or lower-income countries, by enhancing access to care with optimized costs. There is a need to establish which and how interventions may be used as an instrument of care in each local deployment of the iCARE-PD model. We put forward a multidisciplinary framework to generate the evidence supportive of its implementation as the standard of care in the future and delineate the core strategies to secure the implementation of this care approach across different health care systems to ensure feasibility and economic sustainability. We envision this model becoming a paradigm of personalized care transferable to people with atypical forms of neurodegenerative parkinsonism.

Gastric carcinoma (GC) represents the most common cause of death in patients with common variable immunodeficiency (CVID). However, a limited number of cases have been characterised so far. In this study, we analysed the clinical features, bacterial/viral infections, detailed morphology and immune microenvironment of nine CVID patients with GC. The study of the immune microenvironment included automated digital counts of CD20+, CD4+, CD8+, FOXP3+, GATA3+ and CD138+ immune cells, as well as the evaluation of PD-L1 expression. Twenty-one GCs from non-CVID patients were used as a control group. GC in CVID patients was diagnosed mostly at early-stage (n = 6/9; 66.7%) and at younger age (median-age: 43y), when compared to non-CVID patients (p < 0.001). GC pathogenesis was closely related to Helicobacter pylori infection (n = 8/9; 88.9%), but not to Epstein-Barr virus (0.0%) or cytomegalovirus infection (0.0%). Non-neoplastic mucosa (non-NM) in CVID-patients displayed prominent lymphocytic gastritis (100%) and a dysfunctional immune microenvironment, characterised by higher rates of CD4+/CD8+/Foxp3+/GATA3+/PD-L1+ immune cells and the expected paucity of CD20+ B-lymphocytes and CD138+ plasma cells, when compared to non-CVID patients (p < 0.05). Changes in the immune microenvironment between non-NM and GC were not equivalent in CVID and non-CVID patients, reflecting the relevance of immune dysfunction for gastric carcinogenesis and GC progression in the CVID population.

O objectivo da Newsletter do Instituto de Saúde Baseado na Evidência (ISBE) é a disponibilização de informação sobre áreas relevantes para a prática clínica, baseada na melhor evidência científica. São localizados estudos relevantes e de alta qualidade, criticamente avaliados pela sua validade, importância dos resultados e aplicabilidade prática e resumidos numa óptica de suporte à decisão clínica. É dada prioridade aos estudos de causalidade – revisões sistemáticas, ensaios clínicos, estudos de coorte prospectivos/retrospectivos, estudos seccionais cruzados e caso‐controlo – incluindo‐se ainda, quando justificado, estudos qualitativos considerados de elevada qualidade metodológica e importância clínica.

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The objective of the present study is to evaluate the relation between the spatial and temporal dynamics of Land Use and Land Cover (LULC) and the hydro-geomorphological processes and their impacts. The study area is the city of Leiria, in central Portugal, within the period 1958–2018 based on the historical record of floods and landslides disasters. The LULC analysis shows an accentuated increase in the artificial areas and a continuous decrease in the agricultural areas. With regard to hydro-geomorphologic disaster occurrences, a total of 124 occurrences were identified, having caused a set of impacts. The obtained results allow one to characterize the artificialization process, its intensity and territorial dispersion, as a consequence of urban sprawl and peri-urbanization, along with its consequences in exposure to hydro-geomorphological processes. The analysis concludes that changing the risk drivers resulted in an increase in frequency and spatial dispersion of hydro-geomorphologic disasters over the analysed period.

Considerando a formação de um imaginário visual em torno de Angola, sobretudo a partir da década de trinta do século XX – abrangendo o espaço, as sociedades e respectivas expressões artísticas – pretende-se neste estudo discutir o impacto das suas representações no campo da pintura, quer durante o período colonial, quer após o desmantelamento do colonialismo enquanto sistema político-administrativo. Para tal são analisados textos e obras de pintores que em Portugal e Angola, irão problematizar esta relação entre estética, ideologia e história, descrevendo vias de adesão, contestação ou desmontagem, demonstrando, simultaneamente, descontinuidades e continuidades entre passado e presente. Considering the development of a visual imagery about Angola, especially from the thirties – which involved space, societies and their artistic expressions – this study aims to discuss the impact of these representations in painting, both during the colonial period and after the dismantling of colonialism, as a political-administrative system. For this, are analysed texts and works of Portuguese and Angolan painters, which discuss the connection among aesthetics, ideology and history, describe adhesions or disruptions, demonstrating simultaneously, the continuities and discontinuities between past and present.

No summary/description provided

Objetivo: Investigar as terapêuticas atualmente utilizadas para tratar o glaucoma associado à polineuropatia amiloidótica familiar (PAF) e sugerir um algoritmo terapêutico, tendo por base a eficácia e risco de complicações de cada abordagem e os antecedentes clínicos do doente. Métodos: Pesquisa de literatura de 01/01/2000 até 14/07/2019, utilizando as bases de dados Web of Science® e PubMed®, utilizando frases associadas à PAF e terapêutica de glaucoma, tendo sido selecionados artigos que abordavam a terapêutica para o glaucoma associados à PAF. A pesquisa resultou em 9 artigos. A informação de cada artigo for compilada com base na abordagem terapêutica, tendo sido depois avaliada e interpretada criticamente. Resultados: A terapêutica médica é eficaz em cerca de um terço dos doentes com glaucoma da PAF, sendo que destes cerca de 70% necessita de terapêutica médica máxima. A trabeculectomia com MMC teve uma sobrevivência cirúrgica ao fim de 3 anos de cerca de 50% com elevadas taxas de complicações e reoperações em estudos de follow-up prolongado. O sucesso relativo da implantação das válvulas de Ahmed (AGV) foi de cerca de 95% num follow-up de 21,3 meses e com uma taxa de complicações e reoperações inferior à de trabeculectomias com MMC. Os olhos vitrectomizados apresentaram maior risco, tanto de desenvolver glaucoma, como de necessitar cirurgia para o glaucoma. O impacto de cirurgias das cataratas prévias não foi claro. Ranibizumab intravitreo, esclerectomia profunda não-penetrante e procedimentos ciclodestrutivos foram descritos como sendo usados para tratar o glaucoma associado à PAF. Conclusões: É necessária vigilância oftalmológica apertada nos doentes com PAF. Uma terapêutica médica primária é uma abordagem inicial apropriada, porém caso se verifique uma progressão do glaucoma, poderá ser necessário uma abordagem cirúrgica, preferivelmente através de uma cirurgia de AGV. Em olhos vitrectomizados, uma abordagem cirúrgica primária deverá ser discutida e considerada.

Atualmente, as mulheres com doenças reumáticas consideram mais facilmente a gravidez devido aos novos avanços na terapêutica e na gestão da doença durante este período, factores que contribuem para melhores resultados na gestação, tanto maternos como fetais. Assim, devemos considerar este facto quando avaliamos o impacto de vários factores na sua qualidade de vida. Os Patient Reported Outcome Measures (PROM’s) são um dos instrumentos chave para avaliar a qualidade de vida, mas não existem muitos PROM’s específicos da gravidez, e a maioria não foi usada neste grupo de doentes. Por estes motivos, realizámos uma análise comparativa entre grávidas sem doença reumática e grávidas com doença reumática para observar possíveis diferenças entre os dois grupos. Desenvolvemos um caderno de colheita para ser preenchido por 40 grávidas, que recorreram a um hospital terciário (Hospital Santa Maria, Centro Hospitalar Lisboa Norte EPE), com e sem doença reumática. Este caderno continha informações sobre dados sociodemográficos, clínicos gerais, história obstétrica atual e prévia e também 8 PROM’s. Os dados foram analisados com recurso ao software SPSS. Os nossos resultados demonstraram diferenças estatisticamente significativas no domínio Saúde Geral do Questionário de Estado de Saúde (SF-36) e tendência a ser significativamente diferente no EuroQol – 5 dimensions (EQ5D), com as grávidas com doenças reumáticas relatando piores resultados. Concluindo, estes resultados sugeriram que o SF-36 poderá ser um bom PROM para avaliar a qualidade de vida em grávidas com e sem doença reumática. No entanto, este trabalho também deixou claro que é necessário continuar a investigação para entender melhor esta situação complexa que é estar grávida e ter uma doença crónica dinâmica e assim tomar decisões clínicas assertivas e úteis para melhorar os cuidados de saúde neste grupo de pacientes.

Os doentes com infecção VIH têm maior risco de AVC, do que os não infectados, sendo o VIH um factor independente preditor de isquemia. É neste contexto, que se apresenta o caso clínico de uma jovem com infecção VIH. Não obstante a doente em causa nunca ter tido sida, realizar terapêutica anti-retroviral de longa data e ter carga viral nula, tem sofrido AVC isquémicos como complicação do VIH. Far-se-á uma discussão do caso, enquadrando-o num dos algoritmos propostos na literatura, nomeadamente num quadro de aneurismas intracranianos, decorrentes de numa vasculopatia não aterosclerótica associada ao VIH. Quanto à abordagem, no caso reportado o plano passou pela manutenção da terapêutica anti-retroviral e controlo dos factores de risco cardiovascular. A doente ficou com seguimento na consulta de Neurologia, para despistar novas manifestações neurológicas, recorrendo também à imagiologia seriada, a fim de perceber a evolução e o grau de comprometimento do sistema vascular.

Recent large wildfires have caused serious environmental and social impacts in different areas of the world, such as Portugal, Greece and Australia. Sociodemographic changes in rural areas and climate change issues create unprecedented and challenging circumstances that call for an adjustment of fire management strategies and planning tools. In this research, we revise the procedure to assess wildfire susceptibility and hazard for mainland Portugal in a structural perspective. Based on a dataset of burned areas covering 44 years and a set of predisposing factors related to topography and landcover, we tested several susceptibility models using the Likelihood Ratio method, to calculate favourability scores. Landcover classes were analysed using national detailed sources and considering different timeframes. Hazard levels were obtained by combining the susceptibility model with the best accuracy and the probability to burn estimated from fire history (1975-2018). The resulting hazard values were classified in 5 levels based on the breaks of the success curve, instead of quantiles as in previous maps, to ensure territorial continuity at different spatial scales. The results show where the combination of terrain features is more favorable to fire propagation. The higher favourability scores were found for shrubland-type vegetation, whereas agricultural areas, cork and holm forests show lower scores. Eucalyptus and maritime pine forests show similar intermediate scores and have increased since 2007. The two highest hazard classes classify correctly 90% of the burned area over 44 years, demonstrating the high accuracy of the model. If integrated in spatial planning instruments, in conjunction with municipal plans, the two most hazardous classes may hinder the expansion of built-up areas. About 2% of the municipalities have more than 90% of their territory classified as hazardous, whereas 32% of the municipalities have, instead, less than 10% of hazardous area. These structural maps are a useful baseline for a long-term approach and can be complemented by estimations regarding the behavior and severity of wildfires, which should be further explored.