Repositório RCAAP

Introduction/aims: Fasciculations can be symptomatic, yet not progress to amyotrophic lateral sclerosis (ALS), a condition categorized as benign fasciculation syndrome (BFS). We aimed to assess electrodiagnostic changes and clinical course over time in patients with BFS. Methods: This was a retrospective review of medical records of patients who were referred because of a suspicion of ALS or who had directly asked for a consultation because of a personal concern regarding ALS. All clinical and electromyography (EMG) investigations were performed by the same neurologist, following an established protocol. In addition, laboratory testing and imaging studies were performed as determined to be clinically necessary. Results: We included 37 subjects (mean age 46 ± 14.7 y, 29 male, 7 healthcare professionals). Most patients had experienced fasciculations in both upper and lower limb muscles (62.2%); the remaining patients had fasciculations only in their lower limbs. EMG in seven subjects showed chronic neurogenic potentials in addition to fasciculation potentials; all of these were older men. Follow-up data were available in 24 patients (median 4.7 y), 21 with repeat EMGs, including all those with neurogenic EMG changes at baseline (median 6.5 y). Two-thirds of patients reported symptomatic improvement: 57.1% of those with abnormal EMG and 61.1% with normal EMG. The EMG changes were stable. Discussion: Prognosis of BFS is favorable, regardless of minor EMG abnormalities. The latter do not necessarily imply progression to ALS.

Transcripts containing premature termination codons (PTCs) can be subject to nonsense-associated alternative splicing (NAS). Two models have been evoked to explain this, scanning and splice motif disruption. The latter postulates that exonic cis motifs, such as exonic splice enhancers (ESEs), are disrupted by nonsense mutations. We employ genome-wide transcriptomic and k-mer enrichment methods to scrutinize this model. First, we show that ESEs are prone to disruptive nonsense mutations owing to their purine richness and paucity of TGA, TAA and TAG. The motif model correctly predicts that NAS rates should be low (we estimate 5-30%) and approximately in line with estimates for the rate at which random point mutations disrupt splicing (8-20%). Further, we find that, as expected, NAS-associated PTCs are predictable from nucleotide-based machine learning approaches to predict splice disruption and, at least for pathogenic variants, are enriched in ESEs. Finally, we find that both in and out of frame mutations to TAA, TGA or TAG are associated with exon skipping. While a higher relative frequency of such skip-inducing mutations in-frame than out of frame lends some credence to the scanning model, these results reinforce the importance of considering splice motif modulation to understand the etiology of PTC-associated disease.

Cardiovascular disease (CVD) remains the world’s number one cause of death, either in developed or in developing countries. Therefore, cardiovascular health should concern every living person in the world. From hereditary conditions to lifestyle habits (such as smoking, eating habits, exercise, and others) and societal and environmental contexts (such as air pollution), our hearts are faced with numerous threats. The World Heart Federation (WHF), which I have the privilege to lead for the next two years, is at the helm of the effort to achieve our high-level ambition of cardiovascular health for everyone by leading and inspiring the cardiovascular community. This gives WHF an obligation and an opportunity to shape the future of cardiovascular health, to lead and anticipate the changes we wish for our patients, the professionals, and the global community. We do that by influencing policies, sharing knowledge, and inspiring action.

Introduction: Chronic pain (CP) negatively impacts the lives of almost 2 billion people worldwide, including approximately 37% of adults in Portugal. As most of these patients are followed by a general practitioner, identifying the prevalence and characterizing the pain of patients who visit primary care units will provide valuable insights into the CP landscape in Portugal. Methods: To achieve this goal, an observational, cross-sectional study was conducted in 58 primary care units of mainland Portugal between June 2017 and March 2018. Interviews were conducted with 8445 patients, and 578 CP patients were characterized. Results: We observed that one third of patients suffered from CP, and of these, approximately one third felt that their pain management was insufficient. Most of the population was 55 years old or older, retired, and had more than three comorbidities. However, age and the number and type of comorbidities were not predictors of pain intensity. Additionally, most of the population had pain or discomfort that hindered their mobility and the performance of their everyday activities. This decrease in the quality of life led to feelings of anxiety and depression, which were associated with pain intensity. Conclusion: Given the high prevalence of CP, strategies to improve the quality of life of these patients and decrease the negative impacts, as well as awareness campaigns to increase the populations' knowledge of this condition, are essential for the suitable and timely treatment of CP.

This work aims to analyse the mediator-event structure and its influence over an artistic intervention through the project intervention model with the population. First, the concept is presented through its theoretical and practical aspects, while identifying and reflecting around national Portuguese and foreign instances of mediator-events. It is intended to understand if the artistic and educational interventions through the project model can benefit a mediator-event program adapted for the co-participation between worlds, studied in the current Portuguese panorama. It is studied how this structure can evolve and contribute to the development of a radical pedagogy through the lenses and ingredients of Maria Acaso (2007) and if it might exist a pedagogical dynamic within a horizontal program within the mediator-event. To this end, the work reflects upon the contributions and limits of the mediator-event and its intervention is analysed, through a qualitative data analysis. A scheme of a mediator-event structure is elaborated, compatible with the development of horizontal programs, associated with arts education in connection to radical pedagogies. In a second phase, the feasibility of radical pedagogy is studie and discussed within the scope of the horizontal program Viagem Sentimental with the Portuguese choreographer Francisco Camacho, a program integrated within the mediator event Festival Todos 18’. This study uses several interviews collected from artists, programmers and participants from Festival Todos 18’ and 19’, as well as notes from a field paper diary, collected over several weeks between June and September 2018, along the programs Viagem Sentimental rehearsals with Francisco Camacho, Conversa com Crianças with Rita Pedro, Vala Comum with Andresa Soares, Bruno Humberto e João Ferro Martins, as well as the sewing workshops organized with Vera Alvelos at Festival Todos 18’ e 19’ in São Vicente, Lisbon. Finally, three ingredients are identified to contribute to an update on the intervention with communities in the area of contemporary cultural production.

The fundamental idea of this theoretical/practical thesis is the invention, and subsequent development, of paper, both as a support and, later, as raw material in art. Paper has been, for centuries, one of the most important acquisitions of humanity. Paper has been, is and will be, both in daily life and in the aesthetic development, at the origin of future countless activities, particularly those of artistic nature. From the Renaissance on, paper has fostered the democratization of art and culture. It has been the vehicle for several paradigmatic changes over time. The scope of the present work is the transition from the Classical Art stage of Paper used as a support, to the Modern Art stage, when it became a medium per se. It is the transition from a contemplative art to a tactile, spatial art interacting with the viewer. This was only made possible due to the physical/chemical properties of paper. The importance of paper as vehicle and as material for painting and sculpture opened up possibilities for new aesthetics and forms of expression in the development of Modern Art. In spite of the technological progress of the Digital Era, there is always a document in paper support to physically register artistic works, which makes us understand the perennial nature of paper in plastic arts. The present thesis is, albeit its historical nature, essentially of scientific nature, about paper as raw material and the plastic and expressive potentialities of its perennial nature. The scope of the practical part of the present research work is the art of Installation and the potential of papermaking technique in plastic arts.

(1) Background: the Miombo woodlands comprise the most important vegetation from southern Africa and are dominated by tree legumes with an ecology highly driven by fires. Here, we report on the characterization of bacterial communities from the rhizosphere of Brachystegia boehmii in different soil types from areas subjected to different regimes. (2) Methods: bacterial communities were identified through Illumina MiSeq sequencing (16S rRNA). Vigna unguiculata was used as a trap to capture nitrogen-fixing bacteria and culture-dependent methods in selective media were used to isolate plant growth promoting bacteria (PGPB). PGP traits were analysed and molecular taxonomy of the purified isolates was performed. (3) Results: Bacterial communities in the Miombo rhizosphere are highly diverse and driven by soil type and fire regime. Independent of the soil or fire regime, the functional diversity was high, and the different consortia maintained the general functions. A diverse pool of diazotrophs was isolated, and included symbiotic (e.g., Mesorhizobium sp., Neorhizobium galegae, Rhizobium sp., and Ensifer adhaerens), and non-symbiotic (e.g., Agrobacterium sp., Burkholderia sp., Cohnella sp., Microvirga sp., Pseudomonas sp., and Stenotrophomonas sp.) bacteria. Several isolates presented cumulative PGP traits. (4) Conclusions: Although the dynamics of bacterial communities from the Miombo rhizosphere is driven by fire, the maintenance of high levels of diversity and functions remain unchanged, constituting a source of promising bacteria in terms of plant-beneficial activities such as mobilization and acquisition of nutrients, mitigation of abiotic stress, and modulation of plant hormone levels.

The motivation for writing this book stems from our engagement with three undeniable trends in the twenty-frst century: a geographical trend of escalating urbanisation in a world shaken by multiple interdependent crises, a political trend of recognising the challenges following from this and placing them centrally into global plans for sustainable development, and thirdly, a trend in science policy of proclaiming the importance of interdisciplinary and transdisciplinary (ITD) research, not least to inform policymaking. While torn between challenges and opportunities, one aspect that seems to unite all urban sustainability agendas is an appeal for transformative change and for knowledge that can make it happen. Our collaborative book, Enabling the City, occupies this inconvenient, uncomfortable, inarticulate space – but a space almost universally acclaimed as necessary to solve the difcult processes and urban challenges of today. This book focuses on how inter- and transdisciplinary processes of knowledge production may contribute to transformation at a local level, inescapably infuenced by global trends.

Osteoarthritis (OA) is the most common form of arthritis affecting more than 500 million people globally. It accounts for more pain and functional disability than any other musculoskeletal disease and is an important source of high societal and economic costs. Although the pathophysiology of OA is poorly understood, the risk factors associated with disease development are well-established. They include age, obesity, sex, previous incidence of joint injuries, meniscal damage, joint instability, malalignment, genetics, bone shape (including anatomical deformities), muscle weakness and sarcopenia, and metabolic disease. Although OA can affect any synovial joint, including joints in the hand, according to studies on the global burden of disease in 2010 and 2017, knee OA represents the greatest societal burden.

O presente estudo teve como objectivo geral conhecer as representações que os alunos do 3º ciclo têm sobre a violência escolar. Mais especificamente, foram consideradas as seguintes questões de estudo: Como se distribuem os alunos pela vitimização na escola? Como se distribuem os alunos pela disrupção escolar? Que relação existe entre as dimensões da vitimização e da disrupção escolar? Que relação existe entre as dimensões da vitimização e o desempenho escolar? Que relação existe entre as dimensões da vitimização e a escolaridade desejada? Como se diferenciam os alunos na vitimização em função da autoridade parental? A amostra incluiu 328 alunos, do distrito de Setúbal, do 3º Ciclo. Como instrumentos de avaliação, foram utilizados três questionários: o PVS, “Peer Victimization Scale”, de Mynard e Joseph (2000), a EDEP, uma “Escala de Disrupção Escolar Professada pelos Alunos”, de Veiga (1996) e um conjunto de perguntas gerais sobre o aluno e seus contextos. A análise dos resultados permitiu responder às questões de estudo, destacando-se, aqui, um grupo de alunos que referem ser vítimas de bullying na escola, especificamente, 21,4% afirmam ser vítimas de agressão verbal, 11,1% agressão social, 7,5% agressão física e 7,1% agressão relativa à propriedade. Observou-se, também, que 19% dos alunos referem ter comportamentos disruptivos dentro da sala de aula, falando sem autorização e estando distraídos. Como esperado, foram encontradas relações significativas entre a vitimização e a disrupção escolar; a vitimização não apareceu significativamente correlacionada com o rendimento escolar nem com a escolaridade desejada. Verificou-se, ainda, que os alunos que são vítimas percepcionam o pai como tendo um tipo de autoridade indiferente. Os resultados aproximam-se de estudos revistos, à luz dos quais foram discutidos. O estudo apresenta, no final, sugestões para novas investigações.

Today’s processes of urbanisation and the significant projected growth and shift of dynamic urbanisation to the South and East all imply complex challenges related to urban development. As a result of the global significance of urban trends, the sustainable development agenda is also changing to reflect this priority – through goal-driven changes. Inter-and transdisciplinary approaches are an expression of depth and degrees of collaboration and diversity, and debates around their need are premised on fundamental questions about the nature and legitimacy of knowledge: what it is, who holds it and who is entitled to contribute to its production. The experience and knowledge within the urban realm could be better integrated into the more recent discussion on transdisciplinarity and transformative science for a more sustainable future. The chapter also presents an overview of the key concepts discussed in this book.

The increasing number of human biomonitoring (HBM) studies undertaken in recent decades has brought to light the need to harmonise procedures along all phases of the study, including sampling, data collection and analytical methods to allow data comparability. The first steps towards harmonisation are the identification and collation of HBM methodological information of existing studies and data gaps. Systematic literature reviews and meta-analyses have been traditionally put at the top of the hierarchy of evidence, being increasingly applied to map available evidence on health risks linked to exposure to chemicals. However, these methods mainly capture peer-reviewed articles, failing to comprehensively identify other important, unpublished sources of information that are pivotal to gather a complete map of the produced evidence in the area of HBM. Within the framework of the European Human Biomonitoring Initiative (HBM4EU) initiative-a project that joins 30 countries, 29 from Europe plus Israel, the European Environment Agency and the European Commission-a comprehensive work of data triangulation has been made to identify existing HBM studies and data gaps across countries within the consortium. The use of documentary analysis together with an up-to-date platform to fulfil this need and its implications for research and practice are discussed.

Background: Previous systematic reviews have not shown clear benefit of glucocorticoids for acute viral bronchiolitis, but their use remains considerable. Recent large trials add substantially to current evidence and suggest novel glucocorticoid-including treatment approaches. Objectives: To review the efficacy and safety of systemic and inhaled glucocorticoids in children with acute viral bronchiolitis. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 12), MEDLINE (1950 to January week 2, 2013), EMBASE (1980 to January 2013), LILACS (1982 to January 2013), Scopus® (1823 to January 2013) and IRAN MedEx (1998 to November 2009). Selection criteria: Randomised controlled trials (RCTs) comparing short-term systemic or inhaled glucocorticoids versus placebo or another intervention in children under 24 months with acute bronchiolitis (first episode with wheezing). Our primary outcomes were: admissions by days 1 and 7 for outpatient studies; and length of stay (LOS) for inpatient studies. Secondary outcomes included clinical severity parameters, healthcare use, pulmonary function, symptoms, quality of life and harms. Data collection and analysis: Two authors independently extracted data on study and participant characteristics, interventions and outcomes. We assessed risk of bias and graded strength of evidence. We meta-analysed inpatient and outpatient results separately using random-effects models. We pre-specified subgroup analyses, including the combined use of bronchodilators used in a protocol. Main results: We included 17 trials (2596 participants); three had low overall risk of bias. Baseline severity, glucocorticoid schemes, comparators and outcomes were heterogeneous. Glucocorticoids did not significantly reduce outpatient admissions by days 1 and 7 when compared to placebo (pooled risk ratios (RRs) 0.92; 95% confidence interval (CI) 0.78 to 1.08 and 0.86; 95% CI 0.7 to 1.06, respectively). There was no benefit in LOS for inpatients (mean difference -0.18 days; 95% CI -0.39 to 0.04). Unadjusted results from a large factorial low risk of bias RCT found combined high-dose systemic dexamethasone and inhaled epinephrine reduced admissions by day 7 (baseline risk of admission 26%; RR 0.65; 95% CI 0.44 to 0.95; number needed to treat 11; 95% CI 7 to 76), with no differences in short-term adverse effects. No other comparisons showed relevant differences in primary outcomes. Authors' conclusions: Current evidence does not support a clinically relevant effect of systemic or inhaled glucocorticoids on admissions or length of hospitalisation. Combined dexamethasone and epinephrine may reduce outpatient admissions, but results are exploratory and safety data limited. Future research should further assess the efficacy, harms and applicability of combined therapy.

Mitochondria are crucial to support synaptic activity, particularly through ATP production and Ca2+ homeostasis. This implies that mitochondria need to be well distributed throughout the different neuronal sub-compartments. To achieve this, a tight and precise regulation of several neuronal cytoskeleton players is necessary to transport and dock mitochondria. As post-mitotic cells, neurons are highly dependent on mitochondrial quality control mechanisms and several cytoskeleton proteins have been implicated in mitophagy. Therefore, all of these processes are orchestrated by the crosstalk between mitochondria and the neuronal cytoskeleton to form a coordinated and tuned symphony.

This chapter develops a proposed framework for urban inter-and transdisciplinary processes. In the framework, competences and dispositions are listed separately on purpose to highlight their potential distinctiveness and relevance, thus making them more clearly visible in the phase of planning for an inter-and transdisciplinary process. The first dimension has four phases that characterise inter-and transdisciplinary processes: co-design, co-production, dissemination and outreach, and continuation. The second dimension includes four enabling conditions: time, competences and dispositions, contexts, and words. For inter-and transdisciplinary projects linked to research funds, time is almost always too short, as the unequal weight given to economic and social time results in the former trumping the latter. The third dimension describes a predisposition to learning as an individual, in teams and in society: a quality that underpins and influences the workings of both the phases and the enabling conditions.

Parasitic diseases, such as sleeping sickness, Chagas disease and malaria, remain a major cause of morbidity and mortality worldwide, but particularly in tropical, developing countries. Controlling these diseases requires a better understanding of host-parasite interactions, including a deep appreciation of parasite distribution in the host. The preferred accumulation of parasites in some tissues of the host has been known for many years, but recent technical advances have allowed a more systematic analysis and quantifications of such tissue tropisms. The functional consequences of tissue tropism remain poorly studied, although it has been associated with important aspects of disease, including transmission enhancement, treatment failure, relapse and clinical outcome. Here, we discuss current knowledge of tissue tropism in Trypanosoma infections in mammals, describe potential mechanisms of tissue entry, comparatively discuss relevant findings from other parasitology fields where tissue tropism has been extensively investigated, and reflect on new questions raised by recent discoveries and their potential impact on clinical treatment and disease control strategies.

The position of the nucleus within cells is a key event during cell migration. The movement and positioning of the nucleus strongly impacts cell migration. Notably, the last two years largely contributed to emphasise the dynamicity of the nucleus-cytoskeleton interactions that occur during cell migration. Nuclei are under continuous tension from opposing intracellular forces and its tether to the cytoskeleton can be regulated at different levels. Interestingly, it was showed how nuclear positioning is highly related to cell function. In most migrating cells, including cancer cells, the nucleus can be the rate limiting step of cell migration and is placed away from the leading edge. By contrast, leukocytes position their nucleus close to the lamellipodia at the leading edge, and the nucleus contributes to drilling through the endothelium. Differences in cell migration in 2D versus 3D environments are also evident. The mechanisms and forces at play during nuclear positioning and translocation are clearly affected by the nature of the substrate. As such nuclear positioning during cell migration can vary between cell types and environments. In this review we aim to give an overview of the latest discoveries in the field revealing how nuclear positioning is tightly regulated, not only by intrinsic nuclear properties, such as deformability, nuclear envelope content or nucleus-cytoskeleton connectivity, but also by the microenvironment.

In the present review, we stress the importance of the purine nucleosides, adenosine and guanosine, in protecting the nervous system, both centrally and peripherally, via activation of their receptors and intracellular signalling mechanisms. A most novel part of the review focus on the mechanisms of neuronal regeneration that are targeted by nucleosides, including a recently identified action of adenosine on axonal growth and microtubule dynamics. Discussion on the role of the purine nucleosides transversally with the most established neurotrophic factors, e.g. brain derived neurotrophic factor (BDNF), glial derived neurotrophic factor (GDNF), is also focused considering the intimate relationship between some adenosine receptors, as is the case of the A2A receptors, and receptors for neurotrophins. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'.

Parasites undergo complex life cycles that comprise a wide variety of cellular differentiation events in different host compartments and transmission across multiple hosts. As parasites depend on host resources, it is not surprising they have developed efficient mechanisms to sense alterations and adapt to the available resources in a wide range of environments. Here we provide an overview of the nutritional needs of different parasites throughout their diverse life stages and highlight recent insights into strategies that both hosts and parasites have developed to meet these nutritional requirements needed for defense, survival, and replication. These studies will provide the foundation for a systems-level understanding of host-parasite interactions, which will require the integration of molecular, epidemiologic, and mechanistic data and the application of interdisciplinary approaches to model parasite regulatory networks that are triggered by alterations in host resources.

The incidence of brain metastases (BM) in cancer patients is increasing. After diagnosis, overall survival (OS) is poor, elicited by the lack of an effective treatment. Monoclonal antibody (mAb)-based therapy has achieved remarkable success in treating both hematologic and non-central-nervous system (CNS) tumors due to their inherent targeting specificity. However, the use of mAbs in the treatment of CNS tumors is restricted by the blood-brain barrier (BBB) that hinders the delivery of either small-molecules drugs (sMDs) or therapeutic proteins (TPs). To overcome this limitation, active research is focused on the development of strategies to deliver TPs and increase their concentration in the brain. Yet, their molecular weight and hydrophilic nature turn this task into a challenge. The use of BBB peptide shuttles is an elegant strategy. They explore either receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) to cross the BBB. The latter is preferable since it avoids enzymatic degradation, receptor saturation, and competition with natural receptor substrates, which reduces adverse events. Therefore, the combination of mAbs properties (e.g., selectivity and long half-life) with BBB peptide shuttles (e.g., BBB translocation and delivery into the brain) turns the therapeutic conjugate in a valid approach to safely overcome the BBB and efficiently eliminate metastatic brain cells.