RCAAP Repository

Purpose: Rapid and effective diagnosis of Legionnaires' disease (LD) cases is extremely important so that timely and appropriate therapy can be provided, thereby lowering the morbidity and mortality rates and reducing the health and economic costs associated with this disease. Methodology: Diagnosis is established solely by microbiological tests. There are several methods available, each with different performance, sensitivity and specificity characteristics, and further understanding is required. Our objective was to assess the accuracy of urinary antigen detection, direct fluorescent antibody (DFA) staining, serological testing and the polymerase chain reaction (PCR) method versus culture analysis (the reference standard) in patients suspected of being infected with Legionella or patients with laboratory-confirmed LD. We performed a MEDLINE search in November 2014. Two authors independently assessed the trials and extracted data. Pooled analysis was performed through Meta-DiSc version 1.4. Result: The inclusion criteria were met by 11 studies. All the studies evaluated PCR and DFA tests to detect Legionella in clinical specimens, comparing them to culture techniques, and were included in the meta-analysis. The pooled sensitivity and specificity for PCR were 83 % [95 % confidence interval (CI): 79-87 %] and 90 % (95 % CI: 88-92 %), respectively. DFA was evaluated in one study and the sensitivity and specificity of this test were 67 % (95 % CI: 30-93 %) and 100 % (95 % CI: 91-100 %), respectively. PCR had high sensitivity and specificity for early diagnosis of LD. Conclusion: Culture analysis is deemed necessary for epidemiological studies, molecular strain typing and antibiotic sensibility evaluations; however, the performance of PCR in recent studies calls for additional, well-designed studies in order to achieve the best standard test, which will enable optimization of the Legionella infection diagnostic.

Aims of the study: To compare the assessment of respiratory decline with conventional tests, measurement of diaphragm compound muscle action potential (CMAP) to phrenic nerve stimulation and diaphragm thickness to ultrasound (US) investigation in amyotrophic lateral sclerosis (ALS) patients followed for a short period of time. Patients and methods: We evaluated in 40 consecutive ALS patients, the clinical functional scale (ALSFRS-R), forced vital capacity (FVC), maximal voluntary ventilation (MVV), maximal inspiratory (MIP) and expiratory (MEP) pressures, sniff nasal inspiratory pressure (SNIP), Diaphragm-CMAP (latency and amplitude) and diaphragm US (maximal and minimal diaphragm thickness during full inspiration and expiration, respectively). Patients were evaluated at study entry and 4 months later. Results: Clinical functional assessment (ALSFRS-R), MEP, SNIP, and Diaphragm-CMAP amplitude declined significantly. Conversely, FVC, MVV, MIP, and diaphragm thickness showed a non-significant decline. We found significant correlations between all variables measured at both evaluation times. Conclusion: In this study, we included patients who might be potentially eligible for a clinical trial and re-evaluated them within 4 months. In this short time, diaphragm thickness as assessed by US is not sensitive to detect changes. However, Diaphragm-CMAP amplitude was confirmed to be a sensitive non-volitional method to measure respiratory function in ALS.

Estudo preliminar sobre o impacto da Ciência Aber-ta em todo o ciclo científico, desde o início da inves-tigação até à sua publicação, procurando conhecer, descrever e explicar as perceções de um conjunto de investigadores face ao ecossistema da Ciência Aberta. Foi usada uma metodologia qualitativa, através da realização de uma entrevista semiestru-turada. Os resultados identificam as dúvidas dos investigadores relativamente ao cumprimento das premissas da Ciência Aberta. A sistematização das suas ideias permite questionar se estes estarão preparados para estas novas experiências no cam-po da ciência e se possuirão as competências para garantir a sua autonomia na identificação de onde publicar, como publicar, como gerir os dados de investigação, como divulgar os resultados da inves-tigação, como e porque escolher canais formais e informais da ciência, como usar as tecnologias em benefício da sua visibilidade e, finalmente, como assegurar a perenidade da sua produção científica. Também a nova linguagem usada na Ciência Aber-ta suscita muitas dificuldades junto dos investigado-res. Criar programas de capacitação destinados aos investigadores é uma meta estratégica nos proces-sos de implementação deste paradigma de ciência.

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As bibliotecas do ensino superior têm sido objeto de investigação nos mais diversos domínios, quer pelo seu papel determinante na construção do espaço das aprendizagens ao nível terciário, quer no estudo e desenvolvimento de políticas ou práticas que são transversais ao roteiro universitário ou politécnico. A análise da sua intervenção é pois de incontornável importância, especialmente para profissionais – que iniciam a sua carreira, ou peritos de reconhecida experiência - quer para outros interessados no tema das bibliotecas universitárias, sendo útil igualmente a decisores, professores e estudantes que se interessam pela área da informação e biblioteconomia em geral. Reconhecendo esse papel fundamental das bibliotecas universitárias, a presente obra procura colmatar uma lacuna nesta área, abrangendo múltiplas perspetivas, que procuram estabelecer pontes entre Portugal e o Brasil, através dos contributos dos diferentes autores. Partindo de uma perspetiva histórica, é feita uma reflexão sobre o papel e o valor das bibliotecas universitárias também na atualidade, nas suas diversas vertentes. Focando-se no contexto da gestão do conhecimento e relacionando as tecnologias, a Ciência Aberta e a investigação, bem como as questões da qualidade e impacto, são aprofundados os principais temas que estruturam as atividades desenvolvidas nestas organizações, incluindo perspetivas de futuro. O livro procura assim dar um contributo para o conhecimento destas matérias tão importantes para a vida académica e para a sociedade em geral, com influências determinantes no bem-estar, desenvolvimento da cidadania e aprendizagem ao longo da vida.

A ideia de mudança perpassa as bibliotecas universitárias o que impele os bibliotecários das instituições do ensino superior a repensar o seu papel e atuação em permanência. Por um lado, a construção de Recomendações para as bibliotecas do ensino superior, procura trazer estabilidade e segurança, criando orientações a serem aplicadas na prática. Por outro, as mudanças no ensino superior, nas tecnologias e recursos eletrónicos, e nas práticas de gestão, podem ser percebidas como elementos desestabilizadores, potenciando inseguranças nas ações desenvolvidas. É apresentado o documento orientador Recomendações para as Bibliotecas do Ensino Superior de Portugal 2020-2022, descrevendo-se o trabalho que esteve na sua origem, bem como a receção por parte dos bibliotecários de ensino superior em Portugal e as suas perspetivas de futuro face à aplicação destas mesmas recomendações. O presente estudo procura refletir sobre a dupla condição das bibliotecas do Ensino Superior na sua procura de equilíbrio entre a estabilidade e a inovação, numa constante adaptação. Conclui-se que a preparação e o planeamento assentes em linhas orientadoras funcionam como estabilizadores, que ancoram as ações desenvolvidas, enquanto que os ventos de mudança permitem a exploração de novos caminhos e práticas, potenciando-se assim um contexto virtuoso de atuação.

Multiple system atrophy (MSA) is characterized clinically by parkinsonism, cerebellar, autonomic, and corticospinal features of variable severity. When the presentation is only parkinsonism, the disease might be difficult to differentiate from Parkinson's disease (PD). We present a case of an 80-year-old man with previous diagnosis of PD. One year after the diagnosis, he had a whiplash cervical trauma due to a tricycle accident caused by a hole in the road. This low-energy trauma caused an unstable C4-C5 cervical fracture with spinal cord injury, which required surgical decompression and stabilization. Neurological examination showed marked postural instability, no rest and postural tremor, finger tapping slowed on the right, spastic tetraparesis (ASIA D) - predominantly on the left side, brisk deep tendon reflexes in the upper and lower extremities, and bilateral extensor plantar response. He also presented with vertical gaze restriction, mild hypometria in horizontal saccades, moderate dysphagia, and dysphonia. As atypical parkinsonism was suspected, he underwent an MRI that revealed conjunction of findings suggestive of parkinsonian-type MSA. In our case, we hypothesize that the loss of postural reflexes, as an early manifestation of MSA, did not allow the patient to have an effective reaction response to a low-energy trauma, resulting in a more severe injury. With this case report, we speculate that the severe spinal lesions caused by minor accidents can be an early sign of postural instability, which may lead to clinical suspicion of neurodegenerative disorder manifested by postural reflexes impairment.

The neurotrophin brain-derived neurotrophic factor (BDNF) mediates activity-dependent long-term changes of synaptic strength in the CNS. The effects of BDNF are partly mediated by stimulation of local translation, with consequent alterations in the synaptic proteome. The ubiquitin-proteasome system (UPS) also plays an important role in protein homeostasis at the synapse by regulating synaptic activity. However, whether BDNF acts on the UPS to mediate the effects on long-term synaptic potentiation (LTP) has not been investigated. In the present study, we show similar and nonadditive effects of BDNF and proteasome inhibition on the early phase of synaptic potentiation (E-LTP) induced by theta-burst stimulation of rat hippocampal CA1 synapses. The effects of BDNF were blocked by the proteasome activator IU1, suggesting that the neurotrophin acts by decreasing proteasome activity. Accordingly, BDNF downregulated the proteasome activity in cultured hippocampal neurons and in hippocampal synaptoneurosomes. Furthermore, BDNF increased the activity of the deubiquitinating enzyme UchL1 in synaptoneurosomes and upregulated free ubiquitin. In contrast to the effects on posttetanic potentiation, proteasome activity was required for BDNF-mediated LTP. These results show a novel role for BDNF in UPS regulation at the synapse, which is likely to act together with the increased translation activity in the regulation of the synaptic proteome during E-LTP.

Parkinson's Disease (PD) is a complex and multifactorial disorder of both idiopathic and genetic origin. Thus far, more than 20 genes have been linked to familial forms of PD. Two of these genes encode for ATP13A2 and alpha-synuclein (asyn), proteins that seem to be members of a common network in both physiological and disease conditions. Thus, two different hypotheses have emerged supporting a role of ATP13A2 and asyn in metal homeostasis or in autophagy. Interestingly, an appealing theory might combine these two cellular pathways. Here we review the novel findings in the interaction between these two proteins and debate the exciting roads still ahead.

Located at the confluence of the Sorraia and Tagus rivers, the Ponta da Erva area receives annually a large number of Barn Owl juveniles during the post-fledging dispersal period. The landscape is composed by pastures and agricultural fields separated by a large system of drainage ditches and fences, providing a suitable foraging habitat for this species. The recent conversion of a large number of fields into rice paddies - a rising tendency - may represent a significant degradation of this habitat. Based on a previous work (Tomé 1994), this study aimed to evaluate the effect of the land use changes through analysis of temporal and spatial variation of the species abundance over the period of post-fledging dispersal. Nocturnal car transects were carried out on a weekly basis, between July, 17, 2009 and February, 11 2010, during the first three and half hours after sunset, along a 22.5 kilometers route covering most of the area. Barn Owl abundance varied during the study period, with a maximum of 2.3 birds/km in August, coinciding with the arrival of juveniles to Ponta da Erva, and a minimum value of 0.178 birds/km in February, in the beginning of the breeding period. Habitat use was studied by performing three binary logistic regression models for summer, autumn and winter, comparing the presences with random locations where owls were absent. Results were similar to those obtained by Tomé (1994), concerning the use of the several biotopes over time, the importance of cereal stubbles, and the negative influence of grazing. In regard to rice paddies, the importance of this biotope increased considerably after harvest, during the autumn. In addition, Barn Owl diet was studied through pellet analysis. The results did not differ markedly from those observed previously by Tomé (1994), highlighting a very significant increase in the consumption of Pelophylax perezi and significant reduction of Crocidura russula.

Distance learning gained publicity and exposure with the pandemic context, attracting more students and the interest of research, consolidating its position of relevance, namely in higher education. This study seeks to reflect on the use of the conceptual map as an active learning strategy, with a view to greater student involvement in a distance university. From the context of a curricular unit with different strategies, which includes, in addition to the traditional reading of documents, the inclusion of videos and or activities in which each student participates in a committed way, it was proposed to use concept maps as powerful tools to engage students. This strategy was aligned with peer feedback. The testimonies left by the students who participated in this case study prove what the literature has said: that the active learning approach based on concept maps positively achieves the objectives and results that aim at successful learning and that the feedback from peers reinforces student self-regulation, enabling insights that improve their learning as a whole.

Brain-derived neurotrophic factor (BDNF) and its high-affinity full-length (FL) receptor, TrkB-FL, play a central role in the nervous system by providing trophic support to neurons and regulating synaptic plasticity and memory. TrkB and BDNF signaling are impaired in Alzheimer's disease (AD), a neurodegenerative disease involving accumulation of amyloid-β (Aβ) peptide. We recently showed that Aβ leads to a decrease of TrkB-FL receptor and to an increase of truncated TrkB receptors by an unknown mechanism. In the present study, we found that (1) Aβ selectively increases mRNA levels for the truncated TrkB isoforms without affecting TrkB-FL mRNA levels, (2) Aβ induces a calpain-mediated cleavage on TrkB-FL receptors, downstream of Shc-binding site, originating a new truncated TrkB receptor (TrkB-T') and an intracellular fragment (TrkB-ICD), which is also detected in postmortem human brain samples, (3) Aβ impairs BDNF function in a calpain-dependent way, as assessed by the inability of BDNF to modulate neurotransmitter (GABA and glutamate) release from hippocampal nerve terminals, and long-term potentiation in hippocampal slices. It is concluded that Aβ-induced calpain activation leads to TrkB cleavage and impairment of BDNF neuromodulatory actions.

Malaria imposes a horrific public health burden - hundreds of millions of infections and millions of deaths - on large parts of the world. While this unacceptable health burden and its economic and social impact have made it a focal point of the international development agenda, it became consensual that malaria control or elimination will be difficult to attain prior to gain a better understanding of the complex interactions occurring between its main players: Plasmodium, the causative agent of disease, and its hosts. Practical and ethical limitations exist regarding the ability to carry out research with human subjects or with human samples. In this review, we highlight how rodent models of infection have contributed significantly during the past decades to a better understanding of the basic biology of the parasite, host response and pathogenesis.

Bone Marrow Tyrosine kinase in the chromosome X (BMX) is a TEC family kinase associated with numerous pathological pathways in cancer cells. Covalent inhibition of BMX activity holds promise as a therapeutic approach against cancer. To screen for potent and selective covalent BMX inhibitors, large quantities of highly pure BMX are normally required which is challenging with the currently available production and purification processes. Here, we developed a scalable production process for the human recombinant BMX (hrBMX) using the insect cell-baculovirus expression vector system. Comparable expression levels were obtained in small-scale shake flasks (13 mL) and in stirred-tank bioreactors (STB, 5 L). A two-step chromatographic-based process was implemented, reducing purification times by 75% when compared to traditional processes, while maintaining hrBMX stability. The final production yield was 24 mg of purified hrBMX per litter of cell culture, with a purity of > 99%. Product quality was assessed and confirmed through a series of biochemical and biophysical assays, including circular dichroism and dynamic light scattering. Overall, the platform herein developed was capable of generating 100 mg purified hrBMX from 5 L STB in just 34 days, thus having the potential to assist in-vitro covalent ligand high-throughput screening for BMX activity inhibition.

γδT cells represent the majority of lymphocytes in several mucosal tissues where they contribute to tissue homoeostasis, microbial defence and wound repair. Here we characterise a population of interleukin (IL) 17-producing γδ (γδ17) T cells that seed the testis of naive C57BL/6 mice, expand at puberty and persist throughout adulthood. We show that this population is foetal-derived and displays a T-cell receptor (TCR) repertoire highly biased towards Vγ6-containing rearrangements. These γδ17 cells were the major source of IL-17 in the testis, whereas αβ T cells mostly provided interferon (IFN)-γ in situ. Importantly, testicular γδ17 cell homoeostasis was strongly dependent on the microbiota and Toll-like receptor (TLR4)/IL-1α/IL-23 signalling. We further found that γδ17 cells contributed to tissue surveillance in a model of experimental orchitis induced by intra-testicular inoculation of Listeria monocytogenes, as Tcrδ-/- and Il17-/- infected mice displayed higher bacterial loads than wild-type (WT) controls and died 3 days after infection. Altogether, this study identified a previously unappreciated foetal-derived γδ17 cell subset that infiltrates the testis at steady state, expands upon puberty and plays a crucial role in local tissue immune surveillance.

Excitotoxicity is a phenomenon that describes the toxic actions of excitatory neurotransmitters, primarily glutamate, where the exacerbated or prolonged activation of glutamate receptors starts a cascade of neurotoxicity that ultimately leads to the loss of neuronal function and cell death. In this process, the shift between normal physiological function and excitotoxicity is largely controlled by astrocytes since they can control the levels of glutamate on the synaptic cleft. This control is achieved through glutamate clearance from the synaptic cleft and its underlying recycling through the glutamate-glutamine cycle. The molecular mechanism that triggers excitotoxicity involves alterations in glutamate and calcium metabolism, dysfunction of glutamate transporters, and malfunction of glutamate receptors, particularly N-methyl-D-aspartic acid receptors (NMDAR). On the other hand, excitotoxicity can be regarded as a consequence of other cellular phenomena, such as mitochondrial dysfunction, physical neuronal damage, and oxidative stress. Regardless, it is known that the excessive activation of NMDAR results in the sustained influx of calcium into neurons and leads to several deleterious consequences, including mitochondrial dysfunction, reactive oxygen species (ROS) overproduction, impairment of calcium buffering, the release of pro-apoptotic factors, among others, that inevitably contribute to neuronal loss. A large body of evidence implicates NMDAR-mediated excitotoxicity as a central mechanism in the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and epilepsy. In this review article, we explore different causes and consequences of excitotoxicity, discuss the involvement of NMDAR-mediated excitotoxicity and its downstream effects on several neurodegenerative disorders, and identify possible strategies to study new aspects of these diseases that may lead to the discovery of new therapeutic approaches. With the understanding that excitotoxicity is a common denominator in neurodegenerative diseases and other disorders, a new perspective on therapy can be considered, where the targets are not specific symptoms, but the underlying cellular phenomena of the disease.

In Europe, which has an influenza vaccination coverage of 45·6%, about 30 million individuals have ischaemic heart disease, and more than half a million of these people will die from cardiovascular causes (figures based on the conservative standardised mortality rates of individuals aged 65 years and older). Considering that influenza vaccination is associated with a 24% risk reduction of cardiovascular mortality in this population (the lower limit of 95% CI of the estimate), an increase of coverage to 75% (as recommended by the European Council) would translate to about 42 000 potentially avoidable cardiovascular deaths in Europe among individuals with ischaemic heart disease.

Este relatório foi realizado no âmbito do Mestrado em Ensino de Geografia, da Universidade de Lisboa e apresenta o resultado de uma sequência letiva didática, através da lecionação do tema “A dinâmica do Litoral”. A sequência foi implementada na Escola Básica de Mafra à turma do 7ºA. O objetivo principal passou por perceber de que forma o estudo a dinâmica do litoral no 7º ano de escolaridade pode sensibilizar para a Educação Ambiental. Assim, é feita uma primeira abordagem à importância do Ensino da Geografia e à crescente preocupação que esta disciplina demonstra para com a proteção e prevenção do ambiente. Para conhecer a realidade portuguesa, no que diz respeito aos desafios relacionados com o litoral e com o ambiente, a estratégia passou pela exploração e análise de imagens vídeos, e da realização de algumas fichas de trabalho e questionários com o intuito de envolver os alunos na compreensão dos problemas sobre o litoral e procura de soluções para os mesmos. Para estimular o desenvolvimento de atitudes de sensibilização para a preservação do ambiente no espaço de vivência dos alunos, foram realizadas duas atividades: a primeira consistia na elaboração de um cartaz onde foram debatidas ideias sobre os problemas que afetam o mar trabalhando o pensamento critico e o pensamento criativo. A segunda atividade está relacionada com a realização de um vídeo, para concurso, com o tema “A importância do mar na minha região”, onde os alunos ficaram a perceber a importância que o mar teve e tem para o desenvolvimento de atividades locais. As estratégias de ensino – aprendizagem adotadas foram implementadas tentando sempre cativar e apelar à participação dos alunos nas aulas facilitando a aprendizagem. Estas passaram pela análise de mapas, imagens, realização fichas de trabalho e exploração e realização de vídeos. Com esta experiência foi possível concluir que o estudo da dinâmica do litoral pode de facto ajudar a sensibilizar os alunos para a Educação Ambiental. Embora estes alunos demonstrassem já alguma preocupação com as questões ambientais, tomaram ainda mais consciência dos problemas e possíveis soluções.

Formation of blood vessel networks by sprouting angiogenesis is critical for tissue growth, homeostasis and regeneration. How endothelial cells arise in adequate numbers and arrange suitably to shape functional vascular networks is poorly understood. Here we show that YAP/TAZ promote stretch-induced proliferation and rearrangements of endothelial cells whilst preventing bleeding in developing vessels. Mechanistically, YAP/TAZ increase the turnover of VE-Cadherin and the formation of junction associated intermediate lamellipodia, promoting both cell migration and barrier function maintenance. This is achieved in part by lowering BMP signalling. Consequently, the loss of YAP/TAZ in the mouse leads to stunted sprouting with local aggregation as well as scarcity of endothelial cells, branching irregularities and junction defects. Forced nuclear activity of TAZ instead drives hypersprouting and vascular hyperplasia. We propose a new model in which YAP/TAZ integrate mechanical signals with BMP signaling to maintain junctional compliance and integrity whilst balancing endothelial cell rearrangements in angiogenic vessels.

O turismo é um dos aspetos da modernidade mais importantes no mundo, com um impacto de extrema importância da economia, às sociedades e culturas, e ao ambiente. No entanto, o crescimento descontrolado do turismo tem vindo a provocar uma série de consequências no ambiente, como o aumento das emissões CO2, a sobre-exploração dos recursos naturais ou a destruição de ecossistemas e habitats naturais. O turismo sustentável e o turismo responsável são conceitos que tentam reduzir esses riscos, mas a sua diminuição deve começar pelas práticas consideradas como comuns e banais, no dia-a-dia de cada pessoa, que reduzem o consumo dos recursos e o desperdício. Considerando que o turismo jovem se encontra em franco crescimento, e que os jovens ditarão o comportamento do futuro, a presente dissertação pretende analisar as atitudes e comportamentos dos jovens face ao ambiente em férias, comparando-os com as práticas realizadas no seu quotidiano. Para tal, foram questionados 356 jovens entre os 18 e 30 anos, de várias nacionalidades, sobre os seus hábitos sustentáveis em ambos os contextos. Os resultados obtidos indicaram que os jovens revelam preocupações com o ambiente e que procuram, em geral, ter comportamentos ecologicamente corretos quer no seu dia-a-dia como em férias, não se observando grandes variações de comportamento naqueles dois contextos. Ainda assim, foram identificados alguns fatores que levam os jovens a não adotar certas práticas sustentáveis em férias, pelo que é necessária uma investigação mais profunda sobre as atitudes e motivações deste grupo-alvo, que vá além das práticas mais genéricas, a fim de criar soluções sustentáveis, credíveis e uma implementação coerente dessas práticas no quotidiano e em férias.