RCAAP Repository

Introdução O núcleo anterior do tálamo (ANT) é o alvo da estimulação cerebral profunda (DBS) no tratamento de pacientes com epilepsia refratária (RE). A ANT-DBS demonstrou eficácia no controlo de crises epiléticas. No entanto, surgiram referências a efeitos adversos, como distúrbios psiquiátricos. Objetivo Avaliar a progressão dos sintomas psiquiátricos e a manifestação de síndromes psiquiátricas de novo, em pacientes submetidos a ANT-DBS. Metodologia Pacientes adultos com RE submetidos a ANT-DBS no CHULN até abril de 2017, capazes de dar consentimento e realizar testes psicológicos, foram selecionados. A frequência das crises foi relatada pelo paciente/cuidador. Os sintomas psiquiátricos foram avaliados pelo Symptom Checklist-90 (SCL-90) previamente e 6, 12, 24, 36 e 60 meses após implantação. As síndromes psiquiátricas foram diagnosticadas pelo ICD-10. Resultados Dez pacientes foram incluídos. O tempo médio de seguimento clínico foi de 4.2 ± 1.17 anos. 70% dos pacientes relataram uma redução das crises. A mediana desta redução foi de 53% em 6 meses e 32.5% na última visita. Verificou-se um Índice Global de Severidade (GSI) basal médio no espectro disfuncional (1.12 ± 0.98), bem como um aumento neste índice e em todas as dimensões do SCL-90 no primeiro ano. Estes valores diminuíram posteriormente. Quatro pacientes (40%) foram diagnosticados com uma síndrome psiquiátrica de novo, dos quais dois tiveram um segundo tipo de episódio diferente, todos no primeiro ano após implantação. Conclusões Este estudo reforça o papel da ANT-DBS no controlo de crises em pacientes com RE e destaca o aumento no GSI de sintomas psiquiátricos e a alta frequência de síndromes psiquiátricas de novo, no primeiro ano. Apesar do pequeno tamanho da amostra, os resultados evidenciam a importância da avaliação psiquiátrica regular e atenta, a fim de proporcionar a melhor qualidade de vida possível a pessoas com RE submetidas a esta técnica de neuromodulação.

A esclerose múltipla é uma doença cada vez mais prevalente e a sua progressão leva a uma incapacidade clínica permanente. A maior parte dos doentes, jovens adultos em vida ativa, identificam fadiga e apatia como os sintomas inespecíficos mais debilitantes, sendo por isso importante explorá-los. No entanto, estes sintomas continuam a ser pouco abordados na avaliação clínica da doença. Neste trabalho, procurou-se relacionar a fadiga com alterações no estado motivacional de doentes com esclerose múltipla. Para tal, recorreu-se a uma tarefa comportamental na qual a tomada de decisão é baseada no conflito esforço-recompensa. Tentou-se comparar o desempenho de doentes com indivíduos saudáveis, assim como de doentes entre si com diferentes características clínicas, níveis de fadiga, apatia e depressão, analisando se o desempenho na tomada de decisão era independente desses condições. Também se procurou correlacionar medidas de fadiga, apatia e depressão em doentes e compará-las com indivíduos saudáveis. Esperava-se encontrar uma disfunção no processo esforço-recompensa perante uma tomada de decisão em doentes com elevadas queixas de fadiga. Tratou-se de um estudo caso-controlo cuja tarefa comportamental foi reproduzida a partir de um estudo idêntico realizado para doentes de Parkinson. Cada participante teve de aceitar ou rejeitar as recompensas que lhe foram propostas, ao longo de um total de 180 ensaios, consoante o nível de esforço que lhe era pedido para exercer por cada recompensa. Esses ensaios consistiram num jogo digital com macieiras, cujos frutos eram as recompensas, onde o esforço foi exercido através de um dinamómetro. Os participantes preencheriam ainda cinco questionários que avaliaram os seus graus de fadiga, apatia, depressão, défice cognitivo e características clínicas da sua doença. Infelizmente, devido à pandemia CoViD-19 que obrigou a cessar atividades presenciais e a regras estritas de distanciamento social, este projeto não pode ser devidamente desenvolvido nem foi possível deduzir qualquer conclusão.

Historicamente, a traqueostomia é um procedimento milenar que se tem vindo a reinventar ao longo das últimas décadas. Os sucessivos avanços na área da medicina têm permitido uma constante evolução das várias considerações a ter em conta no que diz respeito a este procedimento. As particularidades anatómicas das vias aéreas e as principais indicações que motivam este procedimento na população pediátrica diferem em grande escala do universo adulto. Apesar de todos os avanços científicos, o momento adequado para a realização do procedimento ainda não é consensual, embora as presentes práticas sejam expostas. Será analisada a importância da colaboração do prestador de cuidados para o sucesso desta terapêutica. Proceder-se-á à exposição dos diferentes tipos de tubos existentes e às particularidades de cada um. Relativamente ao procedimento em si, a abordagem cirúrgica permanece o método de escolha na população pediátrica, mantendo, não obstante, a traqueostomia percutânea também o seu lugar na prática clínica. Posteriormente apresenta-se uma exposição das nuances dos diversos cuidados a realizar após a traqueostomia, desde a humidificação e aspiração destes doentes às válvulas de comunicação. Embora estas crianças apresentem uma carga muito mais elevada de morbimortalidades que a restante população, esta é grandemente devida às patologias de base. Todavia, serão analisados os principais eventos adversos que se associam ao procedimento, bem como o modo como deverão ser prevenidos. Por fim, será desconstruída a complexidade do processo de descanulação destes doentes, abordando as melhores práticas, bem como os fatores preditores de uma descanulação bem-sucedida, à luz da melhor evidência atual. O principal objetivo desta revisão de literatura será a apresentação das melhores práticas e avanços na área, relativamente a cada um dos parâmetros apresentados deste procedimento verdadeiramente complexo e multidisciplinar.

No summary/description provided

Klebsiella pneumoniae (Kp) é uma bactéria Gram negativo, frequentemente responsável por infecções nosocomiais. As infecções por estirpes de Kp produtoras de carbapenemases (KpPC) são particularmente relevantes, dada a sua mortalidade elevada, prevalência crescente e opções terapêuticas limitadas. O principal factor de risco para o desenvolvimento de infecção por KpPC é a colonização prévia. O Giannella Risk Score (GRS) é um score preditor de risco de infecção por esta bactéria em doentes colonizados. Os doentes hemato-oncológicos são um grupo particularmente vulnerável. Contudo, nenhum estudo tentou ainda validar este score especificamente para esta população. Com o intuito de validar o GRS na população de doentes hemato-oncológicos e definir um ponto de corte ideal para diferençar doentes de alto e baixo risco de infecção por KpPC, realizou-se um estudo retrospectivo numa coorte de doentes do serviço de Hematologia do Centro Hospitalar Universitário de Lisboa Norte com colonização por KpPC entre Julho de 2018 e Dezembro de 2019. A capacidade preditora do score foi avaliada pelo cálculo da área debaixo da curva receiver operating characteristic (AUROC) e o ponto de corte ideal foi determinado pelo Índice de Youden. Obteve-se informação clínica de 51 doentes, 15 dos quais desenvolveram infecção por KpPC. A aplicação do GRS a esta coorte demonstrou uma AUROC de 0,69 (IC 95%, 0,52-0,87), com ponto de corte ideal em GRS≥6 e GRS<6 (sensibilidade 46,67%, especificidade 91,67%) para doentes de alto e baixo risco, respectivamente. Com este resultado, o score consegue identificar um grupo de doentes de alto risco, que tem maior probabilidade de beneficiar de terapêutica empírica activa contra KpPC, mas não identifica, com clareza, um grupo de baixo risco, no qual se poderia poupar a utilização de antibióticos. Os resultados validam o GRS para a população de doentes hemato-oncológicos, embora com menos capacidade preditora que os estudos realizados na população geral. Mais investigação, incidindo sobre factores de risco mais adequados para prever infecções por KpPC nesta população, bem como o custo-efectividade de alguns procedimentos, poderiam complementar o trabalho.

Lições históricas como Chernobyl, Fukushima ou o colapso da ponte de Mississípi revelam a vital importância da gestão de risco. Para além de saber gerir o risco, as empresas têm de desenvolver planos para se precaverem e oferecerem resiliência a qualquer ameaça que possam enfrentar, desde desastres naturais e terrorismo a ciberataques e propagação de vírus. Estes planos são denominados de planos de continuidade de negócio. A crucialidade destes planos e a introdução de novas leis como Lei Sarbanes-Oxley, Diretiva Europeia 2006/43/EC VIII e recentemente do Regulamento de Protecção de Dados geraram uma maior preocupação e sensibilidade nas empresas em aglomerar todos estes processos de governança, risco e conformidade (GRC). GRC integra a implementação da gestão de risco, planos de continuidade de negócio, conformidade com as leis e boas práticas de auditoria externa e interna. As empresas necessitam de uma ferramenta que ofereça uma visão global da Governança, Risco e Conformidade. No entanto, estas ferramentas são por norma dispendiosas, o que faz com que pequenas e médias empresas não tenham meios para suportar o custo. Consequentemente, estas empresas tendem a adoptar ferramentas de código aberto, como SimpleRisk, Envelop ou Eramba. Apesar de suportarem o GRC, existem vários problemas com as aplicações deste tipo, como a falta de manutenção, problemas de migração, dificuldade de escalabilidade, a necessidade constante de fazer atualizações e a grande curva de aprendizagem associada. A Ernst & Young agora conhecida como EY oferece serviços de Consulting, Assurance, Tax e de Strategy and Transaction para ajudar a resolver desafios mais difíceis dos seus clientes e criar valor. Para se preparar para uma futura auditoria, um cliente da EY pertencente ao sector bancário procura ser certificado em ISO/IEC 27001 e ISO/IEC 22301, referentes a Sistema de Gestão de Segurança de Informação (SGSI) e Sistema de Gestão de Continuidade de Negócio (SGCN), respectivamente. Adicionalmente, o cliente visa migrar a sua infraestrutura no local para uma infraestrutura na cloud. Com todos estes fatores em conta, a EY recomendou uma ferramenta de código aberto de GRC chamada Eramba. Esta tese propõe um estudo profundo das vulnerabilidades que o Eramba pode oferecer assim como uma solução para as resolver através de armazenamento em nuvem. Seguindo uma metodologia de pentesting chamada PTES para o estudo de vulnerabilidades foi possível identificar dez vulnerabilidades sendo quase todas de baixo nível. A metodologia PTES recomenda o uso de adoção de modelo de ameaças de modo a perceber como os processos estão correlacionados, onde estão armazenados dados importantes, quais são os principais ativos e como é processado um pedido na aplicação. Para fazer esta modelação foi seguido uma metodologia proposta pela Microsof nomeada de STRIDE, esta metodologia é uma mnemónica para Spoofing, Tampering, Repudiation, Information Disclosure, Denial of Service e Elevation of Privilege. A Microsoft propõe um modelo de ameaças em quatro passos: modelação do sistema através de Data Flow Diagrams; encontrar ameaças e consequentemente classificá-las através da nomenclatura STRIDE; endereçar ameaças mitigando e eliminando-as e validar se cada uma foi realmente endereçada com sucesso. De modo a endereçar estes dois últimos passos e para conjugar com os requisitos da empresa de migração para armazenamento na nuvem foi desenvolvido uma solução de tornar o Eramba num container para então usufruir da orquestração de containers que é o Kubernetes. Como resultado, a partir do trabalho desenvolvido é possível que qualquer organização adapte esta solução de GRC e consiga hospedar na nuvem sem enfrentar dificuldades. Este trabalho proporcionou analisar a viabilidade da ferramenta Eramba a longo prazo por qualquer organização e perceber se este é escalável.

Introduction: Birth weight is a major contributor to neonatal morbidity and mortality and is associated with chronic diseases in adulthood. This study aimed to evaluate the use of Intergrowth 21st instead of the Fenton & Kim 2013 growth charts in the diagnosis of small and large for gestational age in a group of Portuguese newborns. Material and Methods: We conducted an analytical and retrospective study to evaluate birth weight of term and preterm newborns using both growth charts. Groups studied: ‘Term-weeks’ and ‘Term-days’ (term newborns with gestational age in weeks and days, respectively), ‘Preterm-weeks’ and ‘Preterm-days’ (preterm newborns with gestational age in weeks and days, respectively). Results: A total of 14 056 newborns were included, 6% preterm. Using the Intergrowth 21st growth charts, the groups ‘Term-weeks’ (n = 12 081), ‘Term-days’ (n = 1118), ‘Preterm-weeks’ (n = 617) and ‘Preterm-days’ (n = 240), classified as small for gestational age according to the Fenton & Kim 2013 growth charts were adequate for gestational age in 52.8%, 57.8%, 37.7% and 9.3% respectively; and 9.2%, 9.2%, 5.9% and 0.6% of adequate for gestational age newborns were large for gestational age, respectively. In the ‘Pretermdays’ group, 7.9% of adequate for gestational age newborns were small for gestational age and 22.2% of large for gestational age newborns were adequate for gestational age, all with gestational age below 231 days. Discussion: The use of the Intergrowth 21st growth charts in this sample resulted in a lower number of newborns being classified as small for gestational age, except in very preterm newborns. Conclusion: Considering the results obtained, we suggest that Portuguese maternity hospitals use the Intergrowth 21st instead of the Fenton & Kim 2013 growth charts. However, more studies are needed to confirm these results.

Orofacial dyskinesias (OFD) in the elderly are often secondary topast dopamine receptor-antagonists, being the commonest manifestation of tardive dyskinesia. In some cases no relevant drug his-tory is found and other metabolic, vascular or toxic conditions should be excluded. We present a case of acquired hepatocerebral degeneration (AHCD) as an example of a rare metabolic cause of OFD.

Rationale: After a cerebral vein thrombosis, there is an increased risk of further venous thromboembolic events. The optimal duration of anticoagulation after cerebral vein thrombosis is unknown. Aim: To compare efficacy and safety of a policy of short- (3–6 months) versus long-term (12 months) anticoagulation (any type venous thromboembolic events) after cerebral vein thrombosis for the prevention of venous thromboembolic events. Sample size estimates: A sample of 1428 patients (749 per arm) allows detecting a reduction from 10 to 5% in the risk of venous thromboembolic event recurrence with 80% power at 5% significance, with 3% dropout rate. Methods and design: An international multicenter, prospective cluster-randomized trial with equal allocation between both interventions (ISRCTN25644448). Each cluster is a participating center, which accepted to be randomly allocated to one of the anticoagulation policies. Eligible patients are adults with radiologically confirmed cerebral vein thrombosis within 30 days, and stable to initiate post-acute anticoagulation. Patients judged by the investigator to be an absolute indication for permanent anticoagulation are excluded. Follow-up is at 6, 12 and 24 months. Study outcomes: Primary efficacy outcome is any symptomatic and confirmed fatal/nonfatal venous thromboembolic event (recurrent-cerebral vein thrombosis or non-cerebral venous thromboembolic event). Primary safety outcomes include bleeding events during treatment periods and death from any cause. Discussion: This study responds to a knowledge gap in the post-acute management of cerebral vein thrombosis patients by comparing short- versus long-term anticoagulation for the prevention of venous thromboembolic event recurrence.

Patients with a Philadelphia chromosome-negative myeloproliferative neoplasm may develop a lymphoproliferative disorder; however, the clinical and molecular determinants and the chronological onset of the two events remain unknown. We herein report the case of a 64-year-old man with concomitant diagnosis of high-risk essential thrombocythemia with evidence of a thrombotic event and high-count monoclonal B-cell lymphocytosis (high-count MBL). The patient harbored a JAK2V617F mutation and one of the most common genetic alterations found in chronic lymphocytic leukemia (CLL) (del 13q), which may represent a sign of disease progression. He was initiated on cytoreductive therapy with hydroxyurea 500 mg 3 times per week and hypocoagulation treatment, and is currently under regular surveillance of MBL without CLL criteria.

Background: In a rare disorder such as Huntington's disease (HD), a global network of clinical trial sites with access to patients speeds up recruitment into clinical trials. The objective was to test the hypothesis that demographics, HTT genotype, clinical spectrum, and progression are similar in HD participants of two large observational HD studies, the European Huntington's Disease Network's European REGISTRY study and the North American COHORT study. Methods: REGISTRY cross-sectional data were available from a total of 7,384 participants (1,125 [15.2%] premanifest and 6,259 [84.8%] manifest HD). COHORT cross-sectional data from 1,499 participants at 44 study sites were available (175 pre-HD [11.7%], 1,324 manifest HD [88.3%]). Participants were assessed clinically using the Unified Huntington's Disease Rating Scale (UHDRS). Longitudinal data were available for total motor score and cognitive performance in more than 50% of REGISTRY participants and more than 70% of COHORT participants. Results: Demographics, HTT genotypes, phenotype, and progression were similar in the two studies. Patients in Europe were prescribed antidyskinetics more frequently, and antidepressants less frequently, than in North America. In either study, participants on antidyskinetic medication had higher UHDRS total motor scores, worse function assessment scores, and worse cognitive scores than those taking antidepressants or no medication. In contrast, motor, function assessment, and cognitive scores were broadly similar in participants taking antidepressants or no medication. The differences in cognitive performances between languages were small. Conclusions: Our data suggest that HD patients, and the way they are assessed, are similar across two continents with different cultures and languages.

Impact of intermittent fasting (IF) on health, aging and disease was recently revisited by de Cabo et al. focusing on the evidence from preclinical and clinical trials showing a broad-spectrum benefit on several health domains. Although a highly relevant and interesting critical discussion was conducted, sleep as a major factor interfering on several cardiovascular and metabolic pathways2 directly and indirectly related with those profits seems to have been forgotten.

The increasing number of technologies inserted into vehicles, allowed the common user to have access to a broad number of utilities that allows driving to be easier, safer and more economical. ABS, GPS, Bluetooth and onboard computer are some of the technologies associated with a recent vehicle. On more experimental ones there is obstacle detection, automatic braking and self-driving technologies, which can be supported by a wireless network connection to further improve their capabilities. That connection allows the transformation of each independent vehicle into nodes in an ad-hoc network. The current challenge is to connect all those vehicles and be able to provide the data needed for their correct functioning in a timely manner. That is the challenge this dissertation will seek to analyse: the possibility to create a reliable vehicular information system for cooperative driving based on the cloud. Cloud-based storage can support an ever changing number of vehicles while still satisfying scalability requirements and maintaining ease of access without the need to maintain a physical infrastructure, as that responsibility is laid upon the provider. To understand which service is the best to host the vehicular information system it was analyzed three services from Amazon Web Services (AWS): S3, EC2 and DynamoDB. Ease of utility, latency, scalability and cost were the main requirements tested as they are the most important aspects for a real-time vehicular information system for autonomous vehicles. After deciding which cloud service would be the most appropriate to implement the vehicular information system, two client models were created that fulfilled a set of requirements. They were based in an already existing algorithm named Two-Step Full Replication which utilizes a group of Key-Value Stores services from various clouds to simulate a shared-memory based on multi-writer, multi-reader (MWMR) registers. This algorithm tolerates Byzantine faults by using Byzantine quorum techniques and integrity and authenticity checks. It was defined and implemented the necessary changes on the algorithm to create usable a client for a vehicular information system. The first model called ”Atomic Snapshot Client”, uses the modified Two-Step Full Replication interface with the Atomic Snapshot algorithm. This model guarantees that the read of the system (snapshot) is done atomically without being adulterated by concurrent writes, sacrificing execution latency. The second model is a faster version of the first one with the objective of obtaining faster responses from the system without overly sacrificing data consistency, which is called ”Fast Snapshot Client”. The main change from the first one is the reduction of the guarantees of the atomic registers to regular ones making the reads (scan) and writes (update) simpler and faster, although removing the atomic snapshot feature. With the analysis of the data collected from experiments performed with this model it was possible to observe a relation between the increase of the scan latency time and the total time spent on the execution of the read and write operations on an application with various clients. To solve this problem a simple garbage collector was implemented, which cleans each register when the number of outdated writes that it contains goes over a specified threshold. This solution, although simple, proved to be effective to reduce each scan time. Finally, a vehicular information system based on the AWS S3 service was implemented. It is composed by two types of clients based on the Fast Snapshot Client, named vehicular client and calculator client. The two types of client work together, where the vehicular clients trade information with the calculator. The calculator client scans the registers of the vehicle clients and writes on its registers the processed data for each vehicular client. The vehicle clients need to write all the relevant data they gather and read the register of their respective calculator client and act according to the data read. Each of the clients was tested separately and analysed in order to discuss the viability of this system in a real-world application as well as possible changes to further improve it.

This report describes the work developed in the Transport-on-Demand (ToD) Planner for MaaS - Resources Management project, at Card4B - Systems, S.A., whose theme is related to public transport and aims to develop solutions that improve the current features of some products. Nowadays, there are essential attributes that we look for in our daily lives, such as quickness, efficiency and flexibility of options. The mobility industry has adapted to this trend by offering integrated and intelligent services. Over the years, services have adapted to the passengers needs and it was then that the Mobility as a Service (MaaS) concept was born. Users have access to a single service that results in the integration of several transport options which, due to the technology advancement, allow them to define their desired origin and destination, previously know the price they will pay for the trip and the duration of it. This project has brought improvements to existing products, such as a web wid get that allows users to consult bus routes and schedules according to the following criteria: career, origin and destination. It is also worth to mention the introduction of a new concept - satellite stop - which acts as a flag for that stop, allowing it to be enabled or disabled. Posteriorly, a screen was developed to allow the drawing of routes that each bus will take, so that later they can be compared to the routes that were executed. Finally, it was necessary to replace a technology that will no longer be supported from 2021, Silverlight. The replacement was made in 2 parts: the first made in Blazor and the second using Javascript and jQuery.

No summary/description provided

Critical infrastructures such as electric power grids, nuclear plants, oil and gas refineries, transportations systems or pharmaceutical industries, play an increasingly important role in our lives due to technological advancement and the precision industry. Traditionally, most of these infrastructures, also called industrial control systems (ICS), are large-scale cyber-physical systems (CPS) which all use supervisory control and data acquisition (SCADA). Over recent years, malicious actors have realized the importance and impact of these infrastructures. Combining this with the deprivation of security features in ICS resulted in a large quantity of high value targets just waiting to be exploited. Since these systems are based on equipment with a really long lifetime and, in most of the cases, have an extremely high availability requirement, its important to, somehow, gather information and perform security tests in order to protect these infrastructures, without compromising a live operation. Normally these infrastructures are very complex and often have a remarkable diversity of equipment, communication protocols and transmission technologies. This thesis presents a portable testbed, PICSEL, which was designed and developed to achieve the following goals: to be a portable testbed testing existing exploits and new security solutions whilst exploring new vulnerabilities within the equipment or the environment. Several requirements were considered in the design of the testbed: for instance, choosing the equipment that allowed for more environment configurations; choosing power supplies that support additional equipment; and designing a static electrical diagram based on each device’s requirements. With these requirements, the testbed must be able to support different types of equipment and architectures, allowing for applications in multiple industries, inside which it can be easily reconfigured. The thesis describes the testbed architecture and discusses the design decisions, presenting two test scenarios that were studied and implemented using PICSEL. In each of these test scenarios, different attacks were performed validating each of the PICSEL goals. Testing known vulnerabilities, testing exploits in the wild and exporting information from PICSEL equipment to an external tool were very important steps to validate the results. Therefore, this thesis provides proof of concept confirming the key value of a modular and reconfigurable testbed, PICSEL.

Harmicines represent hybrid compounds composed of β-carboline alkaloid harmine and cinnamic acid derivatives (CADs). In this paper we report the synthesis of amide-type harmicines and the evaluation of their biological activity. N-harmicines 5a–f and O-harmicines 6a–h were prepared by a straightforward synthetic procedure, from harmine-based amines and CADs using standard coupling conditions, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo [4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) and N,N-diisopropylethylamine (DIEA). Amide-type harmicines exerted remarkable activity against the erythrocytic stage of P. falciparum, in low submicromolar concentrations, which was significantly more pronounced compared to their antiplasmodial activity against the hepatic stages of P. berghei. Furthermore, a cytotoxicity assay against the human liver hepatocellular carcinoma cell line (HepG2) revealed favorable selectivity indices of the most active harmicines. Molecular dynamics simulations demonstrated the binding of ligands within the ATP binding site of PfHsp90, while the calculated binding free energies confirmed higher activity of N-harmicines 5 over their O-substituted analogues 6. Amino acids predominantly affecting the binding were identified, which provided guidelines for the further derivatization of the harmine framework towards more efficient agents.

This study aimed to analyse the cross-sectional and prospective relationship between moderate and vigorous physical activity (PA) and depression symptoms. This study analysed 32,392 European late middle-aged to older adults, from 14 European countries across a 4-year follow-up. Data was collected in the fourth (in 2011) and sixth (in 2015) wave, from the Survey of Health, Ageing and Retirement in Europe (SHARE). For the present analysis, participants were considered who responded to the EURO-D 12-item scale of depression symptoms and reported the intensity and frequency of PA. ANCOVAs were conducted to assess the cross-sectional and prospective associations. For both men and women, engaging in moderate or vigorous PA in 2011 was associated with a lower score of depression in 2011 and 2015. From the prospective analysis, moderate and vigorous PA in 2011 was inversely associated with the score of depression. This association remains significant in the fully adjusted for self-rated health, sociodemographic characteristics, and the presence of chronic diseases. Moderate and vigorous PA at least once a week is negatively related to the score of depression, both in men and women. PA is negatively associated with depression symptoms, and from prospective analysis PA predicts lower depression scores 4 years later.

Aedes albopictus, along with Ae. aegypti, are key arbovirus vectors that have been expanding their geographic range over the last decades. In 2017, Ae. albopictus was detected for the first time at two distinct locations in Portugal. In order to understand how the Ae. albopictus populations recently introduced in Portugal are genetically related and which is their likely route of invasion, we performed an integrative cytochrome C oxidase I gene (COI)- and mitogenome-based phylogeographic analysis of mosquitoes samples collected in Portugal in 2017 and 2018 in the context of the global Ae. albopictus diversity. COI-based analysis (31 partial sequences obtained from 83 mosquitoes) revealed five haplotypes (1 to 5), with haplotype 1 (which is widely distributed in temperate areas worldwide) being detected in both locations. Haplotypes 2 and 3 were exclusively found in Southern region (Algarve), while haplotype 4 and 5 were only detected in the North of Portugal (Penafiel, Oporto region). Subsequent high discriminatory analyses based on Ae. albopictus mitogenome (17 novel sequences) not only confirmed a high degree of genetic variability within and between populations at both geographic locations (compatible with the Ae. albopictus mosquito populations circulating in Europe), but also revealed two mitogenome mutational signatures not previously reported at worldwide level. While our results generally sustain the occurrence of multiple introduction events, fine mitogenome sequence inspection further indicates a possible Ae. albopictus migration within the country, from the Northern introduction locality to the Southern region. In summary, the observed scenario of high Ae. albopictus genetic diversity in Portugal, together with the detection of mosquitoes in successive years since 2017 in Algarve and Penafiel, points that both Ae. albopictus populations seem to be already locally established, as its presence has been reported for three consecutive years, raising the public health awareness for future mosquito-borne diseases outbreaks.

The NineTeen Complex (NTC), also known as pre-mRNA-processing factor 19 (Prp19) complex, regulates distinct spliceosome conformational changes necessary for splicing. During Drosophila midblastula transition, splicing is particularly sensitive to mutations in NTC-subunit Fandango, which suggests differential requirements of NTC during development. We show that NTC-subunit Salsa, the Drosophila ortholog of human RNA helicase Aquarius, is rate-limiting for splicing of a subset of small first introns during oogenesis, including the first intron of gurken Germline depletion of Salsa and splice site mutations within gurken first intron impair both adult female fertility and oocyte dorsal-ventral patterning, due to an abnormal expression of Gurken. Supporting causality, the fertility and dorsal-ventral patterning defects observed after Salsa depletion could be suppressed by the expression of a gurken construct without its first intron. Altogether, our results suggest that one of the key rate-limiting functions of Salsa during oogenesis is to ensure the correct expression and efficient splicing of the first intron of gurken mRNA. Retention of gurken first intron compromises the function of this gene most likely because it undermines the correct structure and function of the transcript 5'UTR.