RCAAP Repository

This report presents the results of the study ‘Financialization of housing in Southern Europe: policy analysis and recommendations’, carried out between August and November of 2020. The study, which focuses on Portugal, Spain, Italy and Greece, is based on a comprehensive review of the scholarly literature on the financialization of housing and on a systematic collection of relevant legislation produced in the four countries. The study identifies six modes of housing financialization and several cross-cutting dimensions: 1) mortgage debt, which links the access to homeownership to finance; 2) mortgage securitization, the use of mortgage portfolios as securities/assets; 3) financialization of social rented housing; 4) financialization of market rental housing; 5) transformation of public or not-for-profit housing companies into financialized companies; 6) financialization of ‘not-for-housing housing’ (NFHH) (Donald and Roling 2019), and in particular short-term rentals (STRs) and empty housing used as investment. 7) cross-cutting issues, that is, regulations, practices and programmes that intersect the previous modes, easing the attraction and penetration of financial capital into housing systems and real estate markets. Based on this framework, the study systematizes the role of the state in housing financialization in Southern Europe, observing a number of ‘waves’ of housing financialization.

Este trabalho aborda o tema dos ossículos de equinodermes do Miocénico da Bacia Neogénica do Tejo-Sado, a partir de amostras provenientes da arriba costeira da Península de Setúbal, nomeadamente Foz do Rego, Fonte da Telha, Olhos d’Água e Lagoa de Albufeira. Complementarmente, foram observadas associações de Nanofósseis calcários dos níveis amostrados para maior precisão biostratigráfica. Foram recolhidas 11 amostras que foram crivadas por via húmida e posteriormente tríadas. Da fracção fina daquelas amostras foram feitas lâminas delgadas para o estudo das associações de Nanofósseis calcários, e para a amostra LAAM4 também para o estudo da possível existência de ossículos de holoturóides de dimensão nanométrica. Em todas as amostras estudadas, a Helicospahera stalis e H. walbersdorfensis estão presentes indicando uma idade Tortoniano Inferior. Apenas as amostras provenientes da Lagoa de Albufeira possuíram conteúdo relevante em Equinodermes. Vários ossículos dos representantes fósseis deste Filo foram encontrados naquela localidade, nomeadamente de equinóides, asteróides, ofiuróides, crinóides e holoturóides. Vários fragmentos de carapaças de Equinodermes irregulares espatangóides foram encontrados, juntamente com dois tipos dos seus espinhos. O seu elevado estado de fragmentação não possibilitou uma identificação específica. Fragmentos de equinóides regulares foram também descobertos. Alguns desses fragmentos foram identificados como pertencendo aos géneros Psammechinus e Genocidaris. Os ossículos de equinodermes asteróides dos géneros Luidia e Astropecten encontram-se presentes, nomeadamente ossículos marginais e ambulacrais. Espinhos e outros ossículos de asteróides não identificados foram também encontrados, não tendo sido possível uma classificação sistemática. O género Ophiura encontra-se representado no sedimento estudado, por diversos dos seus ossículos. Foi também possível fazer a distinção de outros ossículos de ofiuróides, não tendo sido possível saber qual a sua espécie. A análise dos cálices de crinóides descobertos possibilitou afirmar que pertencem ao género Palaoantedon. Outros ossículos de crinóides estão também presentes, nomeadamente ossículos dos cirrais e braquiais, englobado-os dentro daquele género.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons (MN) with currently limited targets and biomarkers. Neuroinflammation is a key player for disease onset/progression and the relationship between MN dysfunction and microglial activation represents a major hallmark. Our recent data demonstrated overactivation of the N9-microglia exposed to exosomes from NSC-34-MNs carrying the SOD1G93A mutation (SOD1G93A-MNs). These mutated MNs and their exosomes were enriched in microRNA(miR)-124. After internalizing these exosomes, N9-microglia exhibited time-dependent polarization and upregulated miR-124. Likewise, soluble factors released by SOD1G93A-MNs produced harmful effects on N9-microglia (upregulation of pro-inflammatory mediators/alarmins and reduced phagocytosis). Considering the paracrine effects that upregulated neuronal miR-124 may have on microglia functional properties through the influence of MN-derived secretome, we anticipate that miR-124 can be an active player for microglia immune-deregulation. We aimed to investigate whether the immune balance/function of spinal microglia is modified by wild-type (WT) or SOD1G93A-MN secretome and if it relates with MN miR-124 upregulation. As miRNAs have been progressively associated to deregulated pathways in ALS, we explored how the modulation of miR-124 in WT/diseased MNs modifies the secretome signature of inflammatory-associated miRNA content. Next, we aimed to clarify differences in microglia feedback to the secretome from WT/mutated MNs to better understand their immunoregulatory action. Since our preliminary data showed the anti-inflammatory benefits of miR-124 modulation in SOD1G93A-MNs in the murine N9-microglia cell line, our ultimate goal was to validate such data in the mice spinal cord (SC) microglia cultures, which better resemble in vivo conditions. We used mixed glial cultures isolated from the SC of 8-day-old WT and SOD1G93A mice, that were maintained for 21 days in vitro (DIV). Microglia were then isolated and used after 2 DIV. Additionally, WT and SOD1G93A-MNs were plated and differentiated for 1 day, when SOD1G93A-MNs were transfected with anti-miR-124 for 12 h and maintained for additional 48 h. Secretomes from WT/SOD1G93A/SOD1G93A anti-miR-124 MNs were collected at 4 DIV, incubated in microglia for 4/24 h and inflammatory/functional mediators were evaluated. We demonstrated that SOD1G93A-MNs have a specific miRNA profile (increased miR-124/miR-125b, decreased miR-146a/miR-21), which was fully recapitulated in mutated MNs secretome, except for miR-125b, probably due to its intracellular retention. These effects were reversed in SOD1G93A anti-miR-124-MNs and reflected in their secretome, validating miR-124 as a driver of such deregulation. Relatively to the influence exerted by the neuronal secretome, both spinal microglia responded similarly to WT MNs secretome, displaying decreased inflammatory-associated markers upon 24 h incubation, suggesting the immunosuppressive action of this secretome. Moreover, we proved that SOD1G93A-MNs secretome has an acute and immunostimulant impact on WT microglia by increasing pro-inflammatory-associated genes and also reducing the expression of markers involved in phagocytosis and intercellular communication. In contrast, these inflammatory-associated markers were decreased in SOD1G93A microglia exposed to SOD1G93A-MN secretome, indicating their inability to mount a reparative response. As we anticipated that miR-124 elevation in SOD1G93A-MNs is partially associated with a secretome exerting microglial phenotypic aberrancies, our next results were directed to assess the microglia regenerative effects after incubation with SOD1G93A-anti-miR-124 MN secretome. Such modulation was able to prevent the upregulation of iNOS/IL-1β/IL-18/HMGB1, observed in WT microglia incubated with mutated MNs-secretome. Overall, this work highlights the impact that MNs and their secretome have in ALS microglia immune balance and dysfunction. Our findings also point out, for the first time, the benefits of downregulating miR-124 in SOD1G93A-MNs as a strategy to prevent paracrine microglia activation and ALS-associated neuroinflammation, using the SOD1G93A mice. Future studies will be performed to validate these data in MNs and microglia generated from ALS patients with familiar and sporadic forms of the disease.

The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) for children in Portugal resulted in significant changes in the serotype distribution of the pneumococcal population responsible for invasive pneumococcal disease (IPD) not only in children, but also in adults, consistent with herd protection. A 23-valent pneumococcal polysaccharide vaccine (PPV23) is also available in Portugal since 1996, although adult uptake is believed to be low. The effect of broader PCV13 uptake in children in adult IPD is currently unknown. We aimed to characterize the pneumococcal population causing adult IPD (≥18 years old) in Portugal after the introduction of PCV13 in the Nacional Immunization Plan for children, in 2015. A total of 1608 Streptococcus pneumoniae isolates were recovered from adult IPD in 61 hospitals in Portugal between 2015 and 2017. These strains were characterized phenotypically (serotyping and antimicrobial susceptibility testing) and by molecular methods (MLST). The results obtained were compared with those from previous studies to assess the effect of PCV13 introduction in Nacional Immunization Plan in the studied population. Among the 1608 isolates, 56 different serotypes were found. The most common serotypes were serotype 8 (17.8%, n=287), 3 (14.7%, n=236), 22F (7.4%, n=119), 14 (6.9%, n=111), 19A (6.2%, n=100) and 9N (4.1%, n=66). Most of the cases corresponded to serotypes exclusively found in the PPV23 (42.4%, n=681). The PCV13 serotypes were responsible for 37.6% (n=605) of the cases, and 7-valent pneumococcal conjugate vaccine (PCV7) serotypes accounted for a small fraction of the cases (14.0%, n=225). Penicillin and erythromycin non-susceptibility were detected in 14.9% (n=239) and 16.4% (n=263) of the bacterial isolates, respectively. PCV7 and serotypes exclusively found in PCV13 were responsible for 51.0% (n=122) and 15.5% (n=37) of the penicillin non-susceptible isolates and 37.6% (n=99) and 19.0% (n=50) of the erythromycin resistant isolates, respectively. Regarding all collection, 31.2% (n=501) of the strains were non-susceptible to at least one of the tested antibiotics, where serotypes 14 and 19A were the most common. MLST analysis was performed in 726 strains, where 56 different clonal complexes were found. PCV13 serotypes presented a high genetic diversity, while serotypes exclusively found in PPV23 and non-vaccine serotypes (NVT) presented a lower genetic diversity. Thirteen major clonal complexes (CC) were defined in this study that accounted for 86.4% (n=627) of the isolates: CC156, CC180, CC433, CC378, CC97, CC235, CC439, CC199, CC260, CC315, CC994, CC30 and CC191. Eleven of the 43 PMEN clones were at least double-locus-variant of 33.6% (n=244) of the isolates, however no significant association was established between clonal complexes and penicillin and erythromycin non-susceptible isolates. Serotyping was also performed using in silico methods, where both approaches (SeroBa and PneumoCAT) were found to be good alternatives to conventional methods for the determination of S. pneumoniae serotypes. Comparison with previous studies revealed an increase in the proportion of serotypes 8 and 12F, while serotypes 1, 12B and 7F decreased. Non-susceptible serotypes 8 and 22F isolates increased, whereas non-susceptible 19A isolates decreased. Although not significant, serotype 3 also presented an increase in the proportion of non-susceptible isolates to some of the antimicrobials tested. Regarding genetic lineages, sequence type (ST) 53 (serotype 8) increased, while ST191 (serotype 7F) and ST276 (serotype 19A) decreased. Even with the introduction of PCV13 in the National Immunization Plan, serotype 3 is still one of the dominant serotypes in adult IPD in Portugal, along with serotypes 14 and 19A (all serotypes present in PCV13). The increase in serotypes that do not belong to PCV13, especially serotype 8, 22F and 9N is also of concern, particularly serotypes 8 and 22F where antimicrobial non-susceptible isolates increased. With these, our data suggests that, in a situation of higher vaccination coverage, PCV13 serotypes are still significant causes of adult IPD, especially serotypes 3. However, serotypes not present in PCV13 have been showing to be an important cause of adult IPD, particularly serotypes 8 and 22F, reinforcing the continuous need for surveillance studies.

A maioria das mortes ocorre após um período longo de doença crónica. Desta forma, é expectável que estes doentes experienciem um período ímpar na sua vida, frequentemente previsível e gradual, composto por verdadeiras alterações, conhecido por morte iminente. A capacidade de identificar os sinais e sintomas que caracterizam esta fase pode ajudar não só a entender melhor a fisiopatologia do processo de morte, mas também ajudar os clínicos a tomar as melhores decisões, de forma a garantir a dignidade e a qualidade de vida que estes doentes necessitam, facilitar a comunicação com as suas famílias e também permitir uma melhor gestão de recursos de saúde. O objetivo deste trabalho foi estudar os sinais e sintomas que ocorrem nos últimos dias de vida num doente crónico. Uma pesquisa de revisão realizada em diferentes bases de dados médicas (PubMed, Cochrane Library e European Journal of Palliative Care) revelou 46 sinais e sintomas que caracterizam o doente perto da morte e as suas prevalências relativamente às últimas 24 horas, 2 dias, 3 dias, 7 dias e 14 dias de vida. Em geral, os resultados obtidos encontram-se em conformidade com estudos anteriores. Contudo, tendo em conta que a definição temporal de morte iminente ainda não se encontra bem estabelecida, é difícil conseguir chegar a uma conclusão definitiva. São necessários mais estudos para ajudar os clínicos a reconhecer o doente na sua fase final de vida.

Introdução: O cancro da mama é a neoplasia maligna mais comum entre as mulheres. A evolução na terapêutica do carcinoma da mama tem ocorrido no sentido do alcance da menor invasividade sem que, no entanto, haja o compromisso da eficácia. Alguns estudos evidenciaram a baixa probabilidade da extensão microscópica das células malignas superior a 1cm da loca tumoral, o que desafia a noção da imperatividade da radioterapia adjuvante convencional associada a cirurgia conservadora, particularmente para as doentes em estádio inicial. A Radioterapia Intraoperatória (RT-IO) corresponde a uma das técnicas de Irradiação parcial acelerada da mama (APBI) que se tem apresentado como uma das possíveis alternativas no tratamento das doentes em estádio inicial. Esta revisão tem como objetivo proceder a revisão da literatura relativa a eficácia do uso terapêutico da RT-IO em substituição a Radioterapia adjuvante convencional na abordagem conservadora do cancro da mama em estádio inicial. Metodologia: Realizou-se uma revisão não sistemática da literatura, com recurso a base de dados Pubmed com os termos Breast cancer, Early stage, Treatmen, Intraoperative radiotherapy. Resultados: Obteve-se um conjunto de 31 artigos potencialmente relevantes, dos quais se incluíram 9, duas Revisões Sistemáticas, dois Ensaios Clínicos de Fase III, dois Ensaios Clínicos de Fase II, dois Estudo Coorte Prospetivo e um Estudo Retrospetivo. Discussão: As evidencias mostram que a RT-IO é equiparável a radioterapia convencional quanto a sobrevida global. A sua eficácia no tratamento do cancro da mama em estádio inicial não é inferior ao tratamento convencional no que se refere ao controlo da doença local. É, no entanto, necessária uma escolha cuidadosa das doentes no sentido de serem selecionadas as de baixo risco. É também importante realçar a necessidade de mais estudos, com maior duração, para a identificação mais precisa deste grupo de doentes.

O choque séptico é das principais causas de doença grave e mortalidade em todo o mundo. É um tipo de choque distributivo que cursa com alterações circulatórias que culminam na hipotensão. Um dos objectivos primários do tratamento do choque séptico é restabelecer a pressão de perfusão de órgão através do início de suporte vasopressor, quando esta não é atingida apenas com a reposição volémica. A noradrenalina é, atualmente, o vasopressor de primeira-linha embora se reconheça a existência de casos de hipossensibilidade adrenérgica ou efeitos adversos com doses mais elevadas. A terlipressina é um pro-fármaco sintético, análogo da vasopressina, com elevada afinidade para os recetores de vasopressina-1, com potencial vasopressor. Neste trabalho tenta-se avaliar o quão eficaz e segura a terlipressina é para tratar o choque séptico. Pesquisaram-se as bases de dados da PUBMED e selecionaram-se ensaios clínicos aleatorizados que utilizaram terlipressina em associação com vasopressores adrenérgicos ou isoladamente em doentes com choque séptico. Nos 5 estudos selecionados não se observou diferença significativa na mortalidade ou no tempo de internamento. A terlipressina foi em todos pelo menos tão eficaz como a noradrenalina a manter a pressão arterial média acima dos 65 mmHg. Os doentes a quem foi administrada terlipressina tiveram menor necessidade de noradrenalina relativamente aos que não receberam terlipressina. Alguns estudos mostram redução dos lactatos séricos e da creatinina sérica. O efeito adverso mais frequentemente reportoado foi isquémia digitial. A terlipressina é um vasopressor não adrenérgico aparentemente tão eficaz a corrigir a hipotensão associada ao choque séptico como a noradrenalina, e com potencial benefício na perfusão de tecidos e função de órgão.

Strokes represent a major cause of morbidity and mortality worldwide. Hypertension is the risk factor with the greatest impact in stroke incidence. Blood pressure (BP) control, as a secondary prevention measure, has a substantial effect on diminishing recurrence of vascular events (stroke included). The optimal BP target in secondary stroke prevention is still controversial and different guidelines from diverse organizations recommend different targets. Data available on risk factors control in European countries is limited and, at least, 5 years old. This study’s objective was to assess in a cohort study whether, in Portugal, patients who recently suffered a stroke have controlled BP. Methods: Adult patients (age >18 years) admitted with a diagnosis of stroke (imagological confirmed), included in the PRECISE-Stroke study online database between January 2017 and May 2020. Patients had their BP assessed on discharge, 3 months and 12 months post-stroke. Posteriorly, we conducted a comparative study of BP control throughout the 12-month follow-up period. Results: 357 patients (42,3% female) were included in this study, mean age of 66 years old. 75,4% of them had controlled BP at discharge. 3- and 12-month post-stroke BP control rate drops down to 52,9 and 51%, respectively. In terms of evolution, only 32,6% of patients had controlled BP in every assessment. One limitation to this work was the loss of follow-up through the 12-month post-stroke period, with just 56% of patients attending both medical appointments. Conclusion: The percentage of patients with controlled BP was higher than previously reported, but it is still not ideal.

The first episode psychosis is a variable syndrome defined by the presence of positive and negative symptoms with a continuous duration of at least one week. Typically it begins in adolescence or young adulthood. The prevalence of tobacco use in patients with first episode psychosis is markedly high, about 59%, higher than in the general population. Most of the existing studies currently refer to patients with chronic psychotic disorders. Thus, there has been crescent interest in understanding the concrete origin of the relationship between tobacco and the first psychotic episode. This systematic review reunites the studies published until March 2018, through a search in Pubmed and Web of Knowledge databases, in order to study three main aims that could contribute to the existence of the relationship between tobacco and first psychotic episode: 1)Tobacco smoking as a potential risk factor to first episode psychosis; 2)Nicotine use in the form of tobacco smoking in first episode psychosis: the self-medication hypothesis; and 3)Tobacco use as a marker of greater illness severity in first episode psychosis. Ten original articles were included, of which: one studied the first topic mentioned above; four studied the second; and the remaining five studied the third hypothesis. This review concludes that the relationship between tobacco and the first psychotic episode is undeniable, and, in spite of being difficult to reach the nature of this association, there was a trend towards a greater contribution of the hypothesis “Tobacco smoking as a potential risk factor to first episode psychosis” comparative to the “Nicotine use in the form of tobacco smoking in first episode psychosis: the self-medication hypotheses”. The last hypothesis "Tobacco as a marker of disease severity" was the one that was most corroborated, with four of the five studies included in this topic supporting this hypothesis. In one study, it is suggested that poor adherence to medication may be a causal factor that mediates the association between smoking and increased severity of the disease. It was found that, although further studies on this associations are necessary, if fully tested, it may be very useful in clinical practice, primarily in a view of prevention and also in the staging of the disease.

A prescrição de um ou mais agentes farmacológicos constitui a forma de terminar a maior parte das consultas médicas. O modo como os medicamentos são utilizados tem consequências óbvias para a saúde dos indivíduos e das populações e para a utilização eficiente dos recursos de saúde disponíveis. Este assunto interessa aos decisores políticos, aos profissionais de saúde, aos doentes e ao público em geral.

Introdução: A malária é uma doença infecciosa causada por um parasita do género Plasmodium, com transmissão associada ao mosquito Anopheles. Atualmente em Portugal, apesar de não existir malária indígena, continuam a ser diagnosticados múltiplos casos anualmente, associados a viajantes e imigrantes com origem em países endémicos. A malária grave, definida pela OMS através de um conjunto de critérios clínicos e laboratoriais, é a forma complicada e potencialmente fatal da doença, sendo as crianças um grupo de risco. Neste trabalho procura-se caracterizar os internamentos por malária grave na UCIPed do HSM/CHULN. Métodos: Estudo retrospetivo com base na consulta dos processos clínicos dos doentes internados em UCIP com malária grave entre janeiro de 2010 e junho de 2020. Foram analisados os dados demográficos, sintomas à apresentação, manifestações clínicas e laboratoriais, tratamento e intervenções. Análise estatística descritiva. Resultados: Foram incluídos oito doentes, entre os 3 e os 17 anos (mediana de 11,5 anos), todos com estadia recente em África e infeção identificada por P. falciparum. Seis doentes eram residentes em países Africanos, e apenas uma criança realizou quimioprofilaxia. Todos os doentes apresentaram febre, anemia e trombocitopenia, as manifestações mais frequentes. Os principais critérios de gravidade foram a presença de choque, hiperparasitemia, lesão renal aguda, acidose metabólica e icterícia. Todos foram tratados com uma associação de quinino com doxiciclina ou clindamicina. Houve necessidade de ventilação invasiva em duas crianças, suporte aminérgico em quatro, suporte transfusional em cinco e expansão de volume em seis. Ocorreu um óbito. Discussão: Esta série ilustra a gravidade potencial da malária e morbimortalidade associada. É essencial manter um elevado grau de suspeição para a doença em crianças com estadia em áreas endémicas e instituir terapêutica atempada, incluindo internamento em cuidados intensivos, em casos de malária grave, pela probabilidade de efeitos adversos da terapêutica e necessidade frequente de suporte de órgão.

This article looks after the specific form of exploitation in contemporary domestic service by a focus on female labour force from the plantation societies’ working class in the global economy of domestic service. The case study of Mauritius relates to the intensification of domestic service use in the context of deindustrialization and global cities’ transnational webs. Rather than exploring domestic service work from the perspective of the social reproduction and domestic economy of the served household, I consider first domestic service as a factor of production of the economic development according to Mauritian postcolonial State’s plan. The analysis of the empirical data collected during an 8 months’ fieldwork period brings together three units of analysis: the national productive context, past and present domestic service relations according to maids and employers’ representations, and the proper maids’ household. These analytical tools give evidence of the modernity of colonial power references in the making of the neoliberal exploitation of women’s time in domestic service, and of the way by which this work has turned a major site of class conflicts. This article aims to contribute to the literature on the transnational forms of exploitation in domestic service, as to the studies on the history of class relations to which the domestic workers belong.

The identification of bilateral ground-glass opacifications on thoracic computed tomography (CT) in the COVID-19 ongoing pandemic, supports the diagnosis of SARS-CoV-2 infection. Although COVID-19 pneumonia may present with this typical imaging pattern, itis importantto highlightthat even in an acute clinical setting this pattern it is a non-specific imaging finding and other conditions such as pulmonary oedema, non-infectious pneumonitis and infectious interstitial pneumonia by other pathogens need to be considered.

Como a percepção da população em geral das praias e dunas como ambientes inúteis e perigosas, mudou para um ambiente desejado, muito procurado para banhos terapêuticos, eventos lúdicos e actividades económicas.

The current pandemic of SARS-CoV-2 came un-expectantly and required unprecedented ability to adapt and quickly put in place the most appropriate response measures to limit the spread of COVID-19 disease, while minimising disruption to society’s essential activities. Some sectors were more capable of adapting and reacting than others. Higher education was one of the sectors where the academic capacity (FIP Development Goal 1) demonstrated was phenomenal, partially attributable to the ability to create partnerships between academia and practice. This editorial provides a description of the major changes put in place in Portugal to ensure the education and training of future graduates in Pharmaceutical Sciences was maintained with the same quality. It also discusses some of the potentially less beneficial long-term impacts of these adaptions to the teaching and assessment methods for the competencies of the workforce of tomorrow.

Background Gene therapies have the potential to be a curative approach to a large number of genetic diseases. However, granting of a positive marketing authorisation does not equal patient access to therapy. Objectives The purpose of this paper is to identify a full set of hurdles potentially preventing patient access to gene therapies based on the available literature. Methods A review of the literature using systematic approach in two distinct databases was performed by identifying relevant, peer-reviewed publications, between 2012 and 2018. Results Seven major topics were identified as potential patient access hurdles, namely affordability, assessment of value, development of therapy, ethical/social factors, evidence generation, operational implementation and regulatory hurdles. From these, 25 additional subthemes were further identified. The most frequently mentioned obstacle in the literature is related to the affordability aspect especially focusing on high cost of therapy (84%) and therapy payment/reimbursement (51%). Importantly, the evidence generation focusing on limited trial outcomes (81%) seems as a strong obstacle in patient access to these therapies. Conclusions A growing number of gene therapies are expected to be developed and made available to patients and healthcare professionals. Improvement of patient access to gene therapies can only be achieved by understanding all hurdles, in a complete and integrated fashion, so that strategies are timely established to ensure gene therapies’ benefits are provided to patients and to the society.

Entre 28 de Julho e 15 de Agosto do ano de 2003, ocorreu em Portugal uma onda de calor muito intensa que afectou todos os distritos do Continente. O período com temperaturas muito elevadas durou dezanove (19) dias. O sistema de vigilância ÍCARO identificou a possibilidade da ocorrência de excesso de mortalidade associada ao calor, tendo a existência de efeitos relevantes sobre a mortalidade sido reconhecida posteriormente. Dadas as consequências adversas para a saúde resultantes das ondas de calor, afigurou- se como fundamental, determinar os seus efeitos face à morbilidade. Este estudo destinou-se a contribuir para uma melhor caracterização dos efeitos das ondas de calor na saúde humana, que se traduzem em internamentos hospitalares. O excesso de internamentos hospitalares durante o período de 28 de Julho a 15 de Agosto de 2003 foi obtido com base na análise das bases de dados dos GDH (Grupos de Diagnósticos Homogéneos) de 2001 a 2003. A estimativa global de excesso de internamentos hospitalares no período da onda de calor (POC) de 2003 situou-se nos 5%, o que representa uma estimativa de 2576 internamentos hospitalares a mais do que o esperado. Para os indivíduos com 75 ou mais anos, os internamentos hospitalares ocorridos em 2003 durante o período da ocorrência da onda de calor foram mais elevados, 28% e 25%, relativamente a 2001 e 2002. A estimativa de excesso situa-se nos 14%, o que representa um excesso de 1213 internamentos hospitalares a mais do que o esperado. Quando comparados o internamento hospitalar de 2003 com o de 2001/2002, o grupo de causas de internamento hospitalar que registou um maior aumento percentual durante a onda de calor foi o das Doenças do Aparelho Respiratório, seguido do grupo das Doenças das Glândulas Endócrinas, Nutrição e Metabolismo e do grupo das Doenças do Aparelho Genitourinário. Os resultados apresentados mostram evidência de que existe de facto um impacto da ocorrência de ondas de calor nos padrões de morbilidade, nomeadamente no número de internamentos hospitalares na população de Portugal continental em geral e na população mais idosa em particular (75 e mais anos). A onda de calor de Agosto de 2003 ocorreu no período em que o número de internamentos hospitalares está em regra no seu ponto mais baixo. O número estimado de internamentos adicionais associados ao calor distribuído por todos os hospitais não terá tido particular expressão em cada um deles. O excesso de internamentos estimado no grupo etário dos 75 ou mais anos representa pelo menos 45% de todo o excesso de internamentos (para toda população), num grupo etário que é apenas usualmente responsável por cerca de 15% dos internamentos.

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49·5 years (SD 10·0; onset) and 58·5 years (11·3; death) in the MAPT group, 58·2 years (9·8; onset) and 65·3 years (10·9; death) in the C9orf72 group, and 61·3 years (8·8; onset) and 68·8 years (9·7; death) in the GRN group. Mean disease duration was 6·4 years (SD 4·9) in the C9orf72 group, 7·1 years (3·9) in the GRN group, and 9·3 years (6·4) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0·45 between individual and parental age at onset, r=0·63 between individual and mean family age at onset, r=0·58 between individual and parental age at death, and r=0·69 between individual and mean family age at death) than in either the C9orf72 group (r=0·32 individual and parental age at onset, r=0·36 individual and mean family age at onset, r=0·38 individual and parental age at death, and r=0·40 individual and mean family age at death) or the GRN group (r=0·22 individual and parental age at onset, r=0·18 individual and mean family age at onset, r=0·22 individual and parental age at death, and r=0·32 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35-62, for age at onset; 61%, 47-73, for age at death), and even more by family membership (66%, 56-75, for age at onset; 74%, 65-82, for age at death). In the GRN group, only 2% (0-10) of the variability of age at onset and 9% (3-21) of that of age of death was explained by the specific mutation, whereas 14% (9-22) of the variability of age at onset and 20% (12-30) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11-26) of the variability of age at onset and 19% (12-29) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates.

Monozygotic twins provide a unique opportunity to better understand complex genetic diseases and the relative contribution of heritable factors in shaping the immune system throughout life. Common Variable Immunodeficiency Disorders (CVID) are primary antibody defects displaying wide phenotypic and genetic heterogeneity, with monogenic transmission accounting for only a minority of the cases. Here, we report a pair of monozygotic twins concordant for CVID without a family history of primary immunodeficiency. They featured a remarkably similar profile of clinical manifestations and immunological alterations at diagnosis (established at age 37) and along the subsequent 15 years of follow-up. Interestingly, whole-exome sequencing failed to identify a monogenic cause for CVID, but unraveled a combination of heterozygous variants, with a predicted deleterious impact. These variants were found in genes involved in relevant immunological pathways, such as JUN, PTPRC, TLR1, ICAM1, and JAK3. The potential for combinatorial effects translating into the observed disease phenotype is inferred from their roles in immune pathways, namely in T and B cell activation. The combination of these genetic variants is also likely to impose a significant constraint on environmental influences, resulting in a similar immunological phenotype in both twins, despite exposure to different living conditions. Overall, these cases stress the importance of integrating NGS data with clinical and immunological phenotypes at the single-cell level, as provided by multi-dimensional flow-cytometry, in order to understand the complex genetic landscape underlying the vast majority of patients with CVID, as well as those with other immunodeficiencies.

Apresentação sobre os processos de dinâmica dunar litoral com exemplos da costa portuguesa.