Repositório RCAAP

Purpose: This prospective cohort study aimed to investigate the short-term soft tissue clinical outcomes and recommendation for evaluation and follow-up after a new hybrid All-on-4 rehabilitation. Methods: Forty consecutively included patients rehabilitated in the complete edentulous atrophic maxillae through a hybrid All-on-4 treatment concept (4 immediate function implants in a combination between zygomatic and conventional implants). Periimplant conditions at zygomatic and conventional implants were compared. Four clinical levels (CLs) were used to classify the presence and severity of periimplant conditions. Results: Four patients withdrew from the study. No significant differences were found for periimplant conditions at zygomatic and conventional implants. The distribution was 28, 2, 1, and 9 patients with CL1, CL2, CL3, and CL4, respectively. Conclusions: Soft tissue clinical outcomes of extramaxillary zygomatic implants and conventional implants seem to follow a similar distribution. The proposed classification system stratifies patients, supports decision making, and with further validation may elucidate recommendations for frequency of recall appointments and intervention to enhance long-term success.

Background: Essential tremor (ET) is a very common movement disorder that has no diagnostic markers. Differentiation with Parkinson's disease (PD) can be clinically challenging in some cases, with a high rate of misdiagnosis. Magnetic resonance imaging (MRI) studies have been able to identify neuromelanin changes in the substantia nigra (SN) of PD patients, but they have thus far not been investigated in ET. In this study, we aimed to characterize neuromelanin-MR signal changes in ET and evaluate its diagnostic accuracy in the differential diagnosis with PD. Methods: The inclusion criteria were patients with ET and untreated "de novo" PD patients; in addition, age-matched controls were enrolled. These were studied with a high-resolution T1-weighted MRI sequence at 3.0 Tesla to visualize neuromelanin. The primary outcomes were the area and width of the SN region with high signal. Results: A total of 15 ET patients and 12 "de novo" PD patients were evaluated. The area and width of the T1 high signal in the SN region were markedly decreased in the PD group compared with the ET and age-matched controls, and a greater decrease was seen in the ventrolateral segment. The neuromelanin measures in the ET group, although slightly lower, were not significantly different from the healthy control group. We obtained a sensitivity of 66.7% and a specificity of 93.3% in discriminating ET from early-stage PD. Conclusions: Neuromelanin-sensitive MRI techniques can discriminate ET from early-stage tremor-dominant PD and can be a useful clinical tool in the evaluation of tremor disorders. © 2015 International Parkinson and Movement Disorder Society.

Family migration is the term used to categorise the international movement of people who migrate due to new or established family ties. People moving for family reasons constitute the largest group of migrants entering OECD countries, ahead of labour and humanitarian migration (OECD, 2017). The study of migrant families cuts across the available legal definitions of family and brings to light emerging forms of living together, gender roles, sexualities, kinship ties, and caregiving practices. This chapter selectively synthesises recent scholarship on family migration, providing insights on the institutionalisation of the field, outlining its approaches and methodologies, and highlighting emerging topics for future research. These include transnational families and how they stay in contact; separated families and deportation; the impact of family migration policies; marriage migration and multi-sited and longitudinal studies used in studying the transformation and diversification of family forms.

Student mobility or student migration? The international (and internal) movement of students displays an equivocal terminology, although the editor of this volume, in presenting us with the title of our chapter, prefers the broader term ‘mobilities’ in contrast to the titles of the other chapters in this section, which are all forms of ‘migration’. So why is it that, when students move—either internationally, or within their own countries—they are not usually seen as ‘migrants’, but as something else? This chapter aims to reflect further on the emergence of the twin concepts of migration and mobility as applied to the movement of students—how the concepts have been deployed in various situations and how they have been conditioned (or not) by different theoretical and methodological approaches to the subject of students’ spatial moves. Given that migration and mobility both connote geographical movement across space and over a range of periods of time, we ‘play’ with this notion of movement and propose the alternative term of student movementation. The chapter is structured in three parts. The first develops the definitional, terminological, and conceptual discussion introduced above. In the second section we survey the various directions in past and ongoing research on international student movementation. The conclusion reflects on gaps in our knowledge in this field. Throughout our account we try to give evidence of the empirical richness of research on students’ international moves by referring to a wide body of literature.

Microwave Imaging (MWI) has been studied to aid early breast cancer detection. Current prototypes in more advanced stages of development include both monostatic or multistatic setups. However, multistatic configurations usually include a high number of antennas which consequently require complex and computationally-intensive signal processing algorithms to ensure a good target detection. We previously presented a novel approach using a dielectric lens which reduces the signal processing burden of multistatic setups, while ensuring good spatial resolution. In this paper, we evaluate this novel setup using an anatomically realistic breast phantom and its capability of selecting targets inside the breast. We show a successful detection of the targets using an artefact removal algorithm based on singular value decomposition when the Bessel beam is centered at the target location.

Esta Newsletter (NL) resulta de uma parceria entre o Instituto de Saúde Baseada na Evidência e a Cochrane Portugal, e tem como objectivo disponibilizar informação sobre áreas importantes para a prática clínica, com base na melhor evidência científica disponível. São incluídos estudos relevantes, criticamente avaliados pela sua validade, importância dos resultados e aplicabilidade prática, resumidos numa óptica de suporte à decisão. É dada prioridade a estudos de causalidade incluindo-se ainda, quando justificado, estudos qualitativos e metodológicos, assim como revisões científicas. O conteúdo da NL é da exclusiva responsabilidade do(s) seu(s) autor(es).

The development of integrated decision-support tools, able to assess multiple hazards at the regional and local scales, is a fundamental step to enhance the preparedness of urban areas to mitigate present and future risks arising from climate change. Understanding multi-hazard risk can help prioritize resilience-increasing actions and disaster prevention measures and form the basis for exploring institutional adjustments that improve stakeholders’ capacities to manage risk. Within this framework, the present research work aims to identify and analyze a set of exposure and buildings’ vulnerability indicators to be used as input to a multi-hazard risk assessment methodology. Exposure is to be measured using a dimensionless score resulting from the quantitative identification of the elements at risk. Regarding the physical vulnerability of buildings, it is to be evaluated on a hazard-by-hazard basis using a large-scale parametric-based vulnerability assessment approach. Finally, the obtained exposure and physical vulnerability indicators are to be put together in order to create different data layers, which are then used to identify hotspot risk areas. The Metropolitan Area of Lisbon, Portugal, is used as a pilot study area to discuss the applicability and potential of the proposed indicators.

O fenómeno da marginalia pessoana, as formas que assume e a intenção que lhe está inerente é o tema deste trabalho, que pretende não só dar a conhecer a intensidade emotiva que caracterizou o processo de leitura de uma vasta biblioteca, como mostrar que as anotações de cada livro são um elemento valioso para a construção de uma identidade literária e que tornam possível aceder aos processos mentais do leitor / anotador em que Pessoa se tornou e aos momentos de interacção com os autores de cada exemplar lido. A análise exaustiva da marginalia de Fernando Pessoa nos livros da sua biblioteca poderá provar ser um auxílio precioso para a reconstrução dos percursos de leitura do poeta, já que os pensamentos expressos nos diversos volumes anotados reflectem preocupações estéticas e literárias que o poeta português manifestaria ao longo da vida na sua própria produção textual. Com este trabalho pretende-se também reconstituir algumas experiências pessoais e uma memória literária e intertextual, demonstrando a intensidade emotiva que caracterizou o processo de leitura dinâmica que Pessoa realizou e apresentando-nos este autor como pensador e interlocutor de cada livro que lia e anotava e como construtor de um percurso de raciocínio e reflexão que foi evoluindo ao longo do tempo e determinou a sua progressão como homem e artista.

As a part of environmental health surveillance programs related to Portuguese solid waste incinerators (SWI), two biomonitoring projects have been established to investigate additional exposure to lead in children under the age of 6 years living in the vicinity of those facilities. The above-mentioned programs, being the only ones in the country that integrate systematic observations on human exposure to heavy metals, have to provide systematic data from Portuguese regions on the extent and pattern of human exposure to heavy metals, namely to lead. The present paper is the third of a series of papers prepared to accomplish that objective in regards to lead exposure as evaluated by measuring lead levels in children under the age of 6 years. Altogether, 250 children from Lisbon and 247 from Madeira Island have already been involved in the investigation. The present study evaluates spatial and temporal trends of lead exposure, based on comparisons of children’s blood lead levels, either stratified by living area (exposed and control groups), or by time of exposure (T0, the baseline time, and T1, after approximately 2 years of regular operation of the facilities). The results obtained correspond to a relatively reduced number of individuals. Possibly for this reason, they are not fully conclusive in relation to whether living in the vicinity of SWI represents an additional risk of higher exposure to lead. Time trends of lead exposure as evaluated by blood lead levels in children also do not show any clear pattern. These conclusions and the fact that altogether around 3% of children from the whole group have blood lead levels X10 mg/dl warrant further investigation in order to clarify the contribution of incinerator emissions to the levels of lead in children and to identify alternative sources for preventive purposes, taking into consideration the relevance of even low lead exposure from a public health perspective, mainly in relation to children.

Cervical cancer is the fourth most common cancer affecting women worldwide, according to the latest IARC release with 528 000 new cases every year. Infection by high-risk human papillomavirus (HPV) is necessary but not sufficient for progression to cancer. Epithelial tissues, the target of HPV infection, are heavily exposed to reactive oxygen species (ROS). Hypochlorous acid (HOCl) is a very potent ROS, and it is produced by myeloperoxidase (MPO). MPO, a lysosomal enzyme expressed in polymorphonuclear neutrophils (PMN), has the potential to kill HPV transformed cells, as a component of an intercellular induced-apoptosis pathway. This enzyme catalyzes the production of HOCl in the presence of hydrogen peroxide (H2O2). The H2O2 produced by the Doderlein's bacillus will interact with MPO, contributing to the intercellular induced-apoptosis pathway. We studied a functional polymorphism in the promoter region of MPO (G463A) and how it may affect the risk of developing cervix cancer. A sample of 100 patients with invasive cervical cancer and 122 control women were genotyped for MPO polymorphism by PCR-RFLP method. The statistical method used was χ(2). We found that women with the GG genotype had lower risk for cervical cancer than the women who displayed the heterozygous genotype GA (OR = 0.546, 95 % CI = 0.315-0.939, p = 0.028, OR = 2.210, 95 % CI = 1.257-3.886, p = 0.008, respectively). The genotype that leads to a higher concentration of ROS (GG) presents itself as a protection factor in comparison to the homozygous genotype (AA). This can be explained by the interaction of HOCl and superoxide of transformed cells that will generate apoptosis-inducing hydroxyl radicals.

The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. By gene expression microarray analysis of T-ALL cells treated with the PI3K inhibitor AS605240, we identified Myc as a prominent downstream target of the PI3K pathway. A significant association was found between the AS605240 gene expression signature and that of glucocorticoid resistance and relapse in T-ALL. AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.

The emergence of drug resistance is a major limitation of current antimalarials. The discovery of new druggable targets and pathways including those that are critical for multiple life cycle stages of the malaria parasite is a major goal for developing next-generation antimalarial drugs. Using an integrated chemogenomics approach that combined drug resistance selection, whole-genome sequencing, and an orthogonal yeast model, we demonstrate that the cytoplasmic prolyl-tRNA (transfer RNA) synthetase (PfcPRS) of the malaria parasite Plasmodium falciparum is a biochemical and functional target of febrifugine and its synthetic derivative halofuginone. Febrifugine is the active principle of a traditional Chinese herbal remedy for malaria. We show that treatment with febrifugine derivatives activated the amino acid starvation response in both P. falciparum and a transgenic yeast strain expressing PfcPRS. We further demonstrate in the Plasmodium berghei mouse model of malaria that halofuginol, a new halofuginone analog that we developed, is active against both liver and asexual blood stages of the malaria parasite. Halofuginol, unlike halofuginone and febrifugine, is well tolerated at efficacious doses and represents a promising lead for the development of dual-stage next-generation antimalarials.

Retracing pathways of historical species introductions is fundamental to understanding the factors involved in the successful colonization and spread, centuries after a species’ establishment in an introduced range. Numerous plants have been introduced to regions outside their native ranges both intentionally and accidentally by European voyagers and early colonists making transoceanic journeys; however, records are scarce to document this. We use genotyping-by-sequencing and genotype-likelihood methods on the selfing, global weed, Plantago major, collected from 50 populations worldwide to investigate how patterns of genomic diversity are distributed among populations of this global weed. Although genomic differentiation among populations is found to be low, we identify six unique genotype groups showing very little sign of admixture and low degree of outcrossing among them. We show that genotype groups are latitudinally restricted, and that more than one successful genotype colonized and spread into the introduced ranges. With the exception of New Zealand, only one genotype group is present in the Southern Hemisphere. Three of the most prevalent genotypes present in the native Eurasian range gave rise to introduced populations in the Americas, Africa, Australia, and New Zealand, which could lend support to the hypothesis that P. major was unknowlingly dispersed by early European colonists. Dispersal of multiple successful genotypes is a likely reason for success. Genomic signatures and phylogeographic methods can provide new perspectives on the drivers behind the historic introductions and the successful colonization of introduced species, contributing to our understanding of the role of genomic variation for successful establishment of introduced taxa.

Até ao momento, vários estudos sugerem uma relação entre os níveis de ferro, a sua regulação, a patogénese e a gravidade da asma. No entanto, não foi possível estabelecer ainda, com significância, uma relação de causalidade entre a homeostasia do ferro e o seu papel na fisiopatologia da asma, podendo a alteração dos níveis de ferro ser uma consequência da inflamação crónica inerente à própria doença. O objetivo deste estudo foi avaliar a existência de uma correlação entre a asma grave e a anemia ferropénica. Foi efetuado um estudo clínico observacional retrospetivo, com base em dados de doentes com diagnóstico de asma grave seguidos no Serviço de Imunoalergologia do Centro Hospitalar Universitário Lisboa Norte até 2019, avaliando-se parâmetros laboratoriais, como hemograma e estudo do metabolismo do ferro. Foram igualmente recolhidos dados referentes a variáveis demográficas, tratamento com corticoterapia sistémica e resultados de questionários de avaliação do controlo da asma (ACT e CARAT). Dos 79 doentes com asma grave seguidos no Serviço de Imunoalergologia do Centro Hospitalar Universitário Lisboa Norte e com estudo do metabolismo do ferro, 2 doentes tinham ferropénia absoluta sem anemia (2,53%), 16 doentes tinham anemia (20,3%), dos quais apenas 7 tinham anemia ferropénica (8,9%). Segundo um estudo publicado em 2016, a prevalência de anemia em Portugal foi de 19,9%, sendo a prevalência de anemia ferropénica variável entre 5,8% e 18,4%, dependendo do valor de referência de ferritina utilizado. Concluindo, não foi possível estabelecer uma relação significativa de causalidade entre a asma grave e a anemia, sendo ela ferropénica ou de outra etiologia. Analisando os resultados deste estudo, pode ser colocada a hipótese do mau controlo da asma grave favorecer o desenvolvimento de anemia ou anemia ferropénica. Não foi possível, no entanto, inferir se a toma de corticosteroides sistémicos poderá favorecer o desenvolvimento de anemia ferropénica.

A leucoencefalopatia multifocal progressiva (LEMP) é uma doença desmielinizante do sistema nervoso central (SNC) caracterizada pela ativação do poliomavírus humano John Cunningham (JCV) em estados de imunossupressão severa, resultando numa apresentação heterogénea de sintomas neurológicos e cognitivos. Apesar de rara na população em geral, apresenta taxas de incidência consideráveis em grupos de risco, com elevada mortalidade e incapacidade progressiva. Apresenta-se o caso de dois doentes com LEMP que desenvolveram síndrome inflamatória de restituição imunológica (SIRI), tendo neste contexto realizado terapia antirretrovírica combinada (TARV) e corticoterapia. Estas medidas demonstram-se benéficas contenção do declínio neurológico e um resultado clínico favorável em termos de sobrevida e limitação funcional. Este trabalho reforça a importância do diagnóstico precoce e do follow-up de grupos de risco, levantando novas questões em relação à ação adjuvante da corticoterapia e ao papel da SIRI no desfecho clínico. Ao longo deste trabalho é efetuada uma revisão da literatura da LEMP e de JCV, procurando expor o enquadramento histórico e epidemiológico, a apresentação clínica, assim como, analisar as abordagens diagnósticas e terapêuticas.

A infeção por vírus da hepatite B tem uma grande prevalência a nível mundial, constituindo um importante problema de saúde pública. Em doentes com infeção crónica ou oculta, a reativação de vírus da hepatite B resultante do tratamento com fármacos imunossupressores e biológicos é uma causa de morbilidade e mortalidade. O objetivo principal desta dissertação é compreender os vários mecanismos associados à reativação de vírus da hepatite B e estratificar o risco consoante a classe farmacológica e a profilaxia. Para tal, procedeu-se a uma revisão da literatura científica publicada. Relativamente à reativação, devem considerar-se dois grupos de doentes, consoante os marcadores serológicos: antigénio HBs positivo ou antigénio HBs negativo e anticorpo anti-HBc positivo. Consoante a serologia e o tipo de terapêutica realizada, é possível determinar o risco de reativação, sendo este superior, se o antigénio HBs for positivo. O algoritmo de monitorização e profilaxia dependerá, tanto do tipo de doente, como do risco de reativação. Em todos os casos de risco elevado, deverá proceder-se à profilaxia antivírica com entecavir ou tenofovir. A profilaxia tem um papel preponderante, diminuindo a incidência da reativação e a severidade da hepatite. Numa situação de hepatite grave, torna-se necessário suspender a terapêutica imunossupressora. Com a emergência de novas terapêuticas biológicas e a ausência de relatos de reativação, é fundamental compreender os seus mecanismos de ação e a probabilidade de sua ocorrência, de modo a realizar-se uma profilaxia ou monitorização eficazes. Há que consciencializar as várias especialidades médicas acerca da reativação e das suas consequências e evitar a suspensão de terapêuticas que são essenciais para a situação médica do doente.

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CONTEXTUALIZAÇÃO: a pupila tem ganho importância na Oftalmologia desde a introdução da cirurgia refrativa e pseudofáquica. A sua avaliação pré-operatória é importante, uma vez que esta estrutura pode condicionar os resultados pós cirúrgicos. OBJETIVOS: fazer uma revisão da literatura acerca dos modelos esquemáticos do olho e o papel da pupila nestes, bem como das características da mesma e as dificuldades na sua medição. Será depois analisada e caracterizada a sua biometria (diâmetro e descentramento), a relação entre si e com o lado da órbita, diâmetro do limbus (WTW) e profundidade da câmara anterior (ACD) na população do Hospital da Luz Lisboa. Os resultados foram comparados com a literatura. RESULTADOS: o diâmetro pupilar (PD) médio foi de 4.109 ± 0.532mm, e a diferença entre olhos direitos e esquerdos foi significativa (p=0.005). ACD e WTW não estavam correlacionados com o PD (Pearson coefficient de 0.06 e 0.087). O descentramento pupilar horizontal (PCX) era de 0.259 ± 0.165mm, o vertical (PCY) de -0.010 ± 0.153mm, e o descentramento absoluto de 0.312 ± 0.144. O PCX e o descentramento absoluto correlacionavam-se com o PD (Pearson coefficient de 0.183 e de 0.174, respectivamente, e p<0.001). CONCLUSÃO: apesar de a pupila não ser contemplada na maioria dos modelos esquemáticos revistos, tem um papel significativo na qualidade de visão. Os resultados mostram valores genericamente similares à literatura, com algumas diferenças e limitações. Condições estandardizadas para pupilometria deviam ser propostas, e a possibilidade da existência de variabilidade inter-populacional dos parâmetros deveria ser testada.

Introduction: Assessment of SARS-CoV-2 seroprevalence may detect the real spread of the virus because antibody data can provide a long-lasting measure of infection. Existing serological studies in Portugal have tested new serology methods, albeit with small sample sizes and a lack the focus on geographical regions with a high rate of infection cases. The aim of this study was to estimate the serological prevalence of SARS-CoV-2 in Vila Nova de Gaia, the most populous municipality in the north of Portugal and one of those most affected during the first pandemic wave. Material and Methods: A cross-sectional observational study was conducted between June 23rd and July 17th, 2020. Included in the cohort were 18- to 74-year-old men and women living in the municipality of Vila Nova de Gaia, who were sampled through a nonprobabilistic quota-based approach. Cases with a previous RT-PCR diagnosis of COVID-19 were excluded. Sociodemographic and clinical information was collected using a self-administered, written questionnaire. Blood samples were collected for serological laboratory analysis to detect and quantify SARS-CoV-2 anti-IgG antibodies. Results: We tested 2754 participants. Our results show a SARS-CoV-2 seroprevalence of 3.03% (95% confidence interval: 2.37% – 3.87%). Being a smoker (odds ratio: 0.382, 95% confidence interval: 0.147 – 0.99) and having symptoms of COVID-19 (odds ratio: 2.480, 95% confidence interval: 1.360 – 4.522) were consistently associated with lower and higher odds of SARS-CoV-2 antibody presence, respectively, regardless of the analytic design. Moreover, without adjusting for any variables, having had contact with an infected person within the household was associated with increased odds of a positive test (odds ratio: 9.684, 95% confidence interval: 4.06 – 23.101); after adjusting, having self-reported chronic diseases (odds ratio: 0.448, 95% confidence interval: 0.213 – 0.941) was associated with decreased odds. Conclusion: This was the first study to estimate the serological prevalence of SARS-CoV-2 in one of the most populous municipalities in Portugal, representing the first step in the development of an epidemiological surveillance system in Portugal, which can help to improve the diagnosis of COVID-19.

O ácido hipocloroso (HOCl) é um oxidante forte produzido por neutrófilos e monócitos activados. Esta espécie reactiva de oxigénio (ROS) é gerada a partir da reacção do H2O2 com o Cl‒, catalisada pelo mieloperoxidase (MPO). Embora a formação de HOCl tenha como finalidade matar os microrganismos invasores dentro do fagossoma, pode ser libertado para fora da célula e levar à lesao dos tecidos, contribuindo para o processo inflamatório. O principal objectivo deste trabalho foi estudar as propriedades anti-inflamatórias de alguns flavonóides (quercetina, morina, apigenina e catequina), em relação à captação de HOCl, gerado por neutrófilos activados ex vivo, bem como os seus efeitos na activação do factor de transcrição NF-κB. Em relação à captação de HOCl, para cada flavonóide obtiveram-se diferentes valores de IC50, determinados através de diferentes métodos de competição: cloração da taurina e oxidação da sonda 3-aminofenilfluoresceína (APF), que foi seguida por espectrofluorimetria e citometria de fluxo. A quercetina e a morina apresentaram uma elevada actividade antioxidante com valores de IC50 semelhantes, uma vez que são compostos análogos e possuem as características estruturais que são determinantes para proteger as reacções de cloração/oxidação mediadas pelo HOCl. A apigenina, apesar de não possuir algumas dessas características estruturais, demonstrou possuir uma elevada capacidade antioxidante, devido à maior hidrofobicidade deste composto, quando comparado com a quercetina e a morina. Estudou-se, também, a capacidade dos flavonóides para induzir alterações na activação do NF-κB em células THP-1 activadas por LPS, usando duas abordagens diferentes. Quando as células foram transfectadas com um plasmídeo acoplado ao gene repórter da luciferase, que continha uma sequência kB de elevada afinidade para o NF-kB, e após activação com LPS, observou-se uma elevada activação do promotor do NF-kB. Na presença de alguns flavonóides (morina, apigenina, catequina e isorramnetina) observou-se uma diminuição na activação do promotor do NF-kB. Através da análise dos extractos celulares, por Western blot, também, se observou que a quercetina e a morina inibiam a activação do NF-kB. Esta resposta foi reflectida em termos da translocação do NF-κB para o núcleo e na inibição da degradação da proteína inibitória do NF-κB (IκB). Estes resultados sugerem que os flavonóides estudados podem exercer efeitos antiinflamatórios, através da captação de HOCl e, alguns deles, através da inibição do NF-kB.