Repositório RCAAP

A Doença de Ménétrier (DM) é uma gastropatia que se assume como um desafio diagnóstico devido à sua raridade, escassez de casos descritos internacionalmente, complexidade fisiopatológica inerente e à falta de critérios diagnósticos precisos, tornando exigente o estabelecimento do diagnóstico diferencial com outras patologias que mimetizam esta entidade. O objetivo do presente trabalho passa por rever e estruturar a literatura de modo a sensibilizar o clínico para o reconhecimento e correta abordagem diagnóstica e terapêutica desta entidade e apropriada gestão do doente. Com esse intuito, é descrito o caso de uma doente de 61 anos que se apresenta com um quadro clínico em que é imperioso considerar não só este diagnóstico como o de diversas Poliposes Gástricas que têm uma apresentação clínica e imagiológica semelhante, mas abordagens distintas num estadio inicial que podem ter impacto no prognóstico a longo prazo.

Biomechanical analysis of pelvic floor dysfunction requires knowledge of certain biomechanical parameters, such as muscle fiber direction, in order to adequately model function. Magnetic resonance (MR) diffusion tensor imaging (DTI) provides an estimate of overall muscle fiber directionality based on the mathematical description of water diffusivity. This work aimed at evaluating the concurrence between pubovisceralis muscle fiber representations obtained from DTI, and the maximum principal stress lines obtained through the finite element method. Seven datasets from axial T2-weighted images were used to build numerical models, and muscle fiber orientation estimated from the DT images. The in-plane projections of the first eigenvector of both vector fields describing muscle fiber orientation were extracted and compared. The directional consistency was evaluated by calculating the angle between the normalized vectors for the entire muscle and also for the right and left insertions, middle portions, and anorectal area. The values varied between 28° ± 6 (right middle portion) and 34° ± 9 (anorectal area), and were higher than the angular precision of the DT estimates, evaluated using wild bootstrapping analysis. Angular dispersion ranged from 17° ± 4 (left middle portion) to 23° ± 5 (anorectal area). Further studies are needed to examine acceptability of these differences when integrating the vectors estimated from DTI in the numerical analysis.

Clinical reasoning (mostly diagnostic reasoning) is made of two sequential steps: firstly, problem-solving - estimating disease probabilities through information from the physical exam and sequential tests, providing new information to refine the probability that the patient has a specific disease. Secondly, decision-analysis - a method that formally integrates the evidence regarding the beneficial and harmful effects of treatment options, considering the patient´s values regarding those effects, requiring knowledge of treatment effects, and whether the benefits outweigh risks and costs. This approach is duly called evidence-based diagnosis.

T-cell acute lymphoblastic leukemia (T-ALL) frequently involves aberrant expression of TAL1 (T-cell acute lymphocytic leukemia 1) and LMO2, oncogenic members of the TAL1 transcriptional complex. Transcriptional activity of the TAL1-complex is thought to have a pivotal role in the transformation of thymocytes and is associated with a differentiation block and self-renewal. The transcription factor Forkhead Box P3 (FOXP3) was recently described to be expressed in a variety of malignancies including T-ALL. Here we show that increased FOXP3 levels negatively correlate with expression of genes regulated by the oncogenic TAL1-complex in human T-ALL patient samples as well as a T-ALL cell line ectopically expressing FOXP3. In these cells, FOXP3 expression results in altered regulation of cell cycle progression and reduced cell viability. Finally, we demonstrate that FOXP3 binds LMO2 in vitro, resulting in decreased interaction between LMO2 and TAL1, providing a molecular mechanism for FOXP3-mediated transcriptional modulation in T-ALL. Collectively, our findings provide initial evidence for a novel role of FOXP3 as a tumor suppressor in T-ALL through modulation of TAL1 transcriptional activity.

Este trabalho teve como objetivo estudar as políticas de formação contínua de professores do ensino primário em Angola entre 2001 e 2020, com enfoque nas medidas levadas a cabo pelo sistema educativo, procurando identificar os referenciais das políticas públicas que estiveram subjacentes às inúmeras mudanças ocorridas durante este período. Para conduzir esta investigação optou-se por desenvolver uma pesquisa de natureza qualitativa fundamentada no paradigma fenomenológico-interpretativo. Tendo em conta os objetivos propostos para esta investigação, o estudo partiu de uma pesquisa arquivística/documental onde foi feita a análise cuidada de documentos oficiais, públicos e privados. Paralelamente foram realizadas entrevistas que de modo geral representaram as técnicas utilizadas em uma investigação naturalista. Os dados mostraram que, no período em análise, foram desenvolvidas diversas medidas que visaram a formação contínua de professores do ensino primário pela iniciativa do Ministério da Educação. A análise dos dados evidenciou como as políticas educativas que visaram a formação de professores são construídas por múltiplos atores para além do Estado, nomeadamente com Instituições Internacionais e Organizações não Governamentais, e transportam um referencial sobre a profissionalidade docente.

Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia, affecting infants and adults worldwide. N. meningitidis is also a common inhabitant of the human nasopharynx and, as such, is highly adapted to its niche. During bacteremia, N. meningitidis gains access to the blood compartment, where it adheres to endothelial cells of blood vessels and causes dramatic vascular damage. Colonization of the nasopharyngeal niche and communication with the different human cell types is a major issue of the N. meningitidis life cycle that is poorly understood. Here, highly saturated random transposon insertion libraries of N. meningitidis were engineered, and the fitness of mutations during routine growth and that of colonization of endothelial and epithelial cells in a flow device were assessed in a transposon insertion site sequencing (Tn-seq) analysis. This allowed the identification of genes essential for bacterial growth and genes specifically required for host cell colonization. In addition, after having identified the small noncoding RNAs (sRNAs) located in intergenic regions, the phenotypes associated with mutations in those sRNAs were defined. A total of 383 genes and 8 intergenic regions containing sRNA candidates were identified to be essential for growth, while 288 genes and 33 intergenic regions containing sRNA candidates were found to be specifically required for host cell colonization. Importance: Meningococcal meningitis is a common cause of meningitis in infants and adults. Neisseria meningitidis (meningococcus) is also a commensal bacterium of the nasopharynx and is carried by 3 to 30% of healthy humans. Under some unknown circumstances, N. meningitidis is able to invade the bloodstream and cause either meningitis or a fatal septicemia known as purpura fulminans. The onset of symptoms is sudden, and death can follow within hours. Although many meningococcal virulence factors have been identified, the mechanisms that allow the bacterium to switch from the commensal to pathogen state remain unknown. Therefore, we used a Tn-seq strategy coupled to high-throughput DNA sequencing technologies to find genes for proteins used by N. meningitidis to specifically colonize epithelial cells and primary brain endothelial cells. We identified 383 genes and 8 intergenic regions containing sRNAs essential for growth and 288 genes and 33 intergenic regions containing sRNAs required specifically for host cell colonization.

We show that formyl benzeno boronic acids (2FBBA) selectively react with N-terminal cysteines to yield a boronated thiazolidine featuring a B-N bond. The reaction exhibits a very rapid constant rate (2.38 ± 0.23 × 102 M-1 s-1) under mild aqueous conditions (pH 7.4, 23 °C) and tolerates different amino acids at the position adjacent to the N-cysteine. DFT calculations highlighted the diastereoselective nature of this ligation reaction and support the involvement of the proximal boronic acid in the activation of the imine functionality and the stabilisation of the boronated thiazolidine through a chelate effect. The 2FBBA reagent allowed the effective functionalisation of model peptides (C-ovalbumin and a laminin fragment) and the boronated thiazolidine construct was shown to be stable over time, though the reaction was reversible in the presence of benzyl hydroxylamine. The reaction proved to be highly chemoselective, and 2FBBA was used to functionalize the N-terminal cysteine of calcitonin in the presence of a potentially competing in-chain thiol group. This exquisite selectivity profile enabled the dual functionalisation of calcitonin and the interactive orthogonal modification of this peptide when 2FBBA was combined with conventional maleimide chemistry. These results highlight the potential of this methodology to construct complex and well-defined bioconjugates.

Human exposure to heavy metals makes it necessary to monitor these elements in the human body if the objective is to relate heavy metal exposure to adverse health effects. In Portugal, biomonitoring projects on heavy metals are being carried out on people living in the vicinity of solid waste incinerators. The projects are being developed in the ambit of two environmental health surveillance programs related to solid waste incineration facilities, one near Lisbon and the other on Madeira Island, that have the main objective of guaranteeing the safeguard of public health in relation to the potential negative impact of incineration processes on human health. These programs are the only ones in the country that integrate a systematic observation of human exposure to heavy metals as determined by the respective body burden in several population groups. Therefore, they are the only ones that are currently able to provide systematic data from Portuguese regions on the extent and pattern of human exposure to this type of pollutants. The present paper is the first of a series of three prepared papers with the objective of presenting and discussing available data. It addresses exposure to lead, cadmium and mercury as determined by their levels in blood of general population adults. Results suggest the effectiveness of source control measures in relation to both incinerators under study, similarly to what has been concluded from previous studies addressing exposure to dioxins. They also show, in relation to the baseline situation, a general significant trend for reduction of exposure to all studied heavy metals. Individuals from Lisbon seem to have a significantly higher body burden of the studied metals than those living in Madeira and, in general, metal exposure in men is significantly higher than in women, with the most relevant exception being the case of higher mercury levels in women, at the baseline and for both communities. Compared with published reference values for similar conditions, blood levels of cadmium, lead, and mercury of the present investigation seem to be relatively higher, in median terms and for extreme values, mainly in the case of cadmium and mercury. In the case of lead the differences are not so marked.

A presente investigação surge como resultado de um estudo empírico realizado no âmbito do Mestrado em Administração Educacional. Tendo em conta o interesse que o tema da gestão intermédia e das lideranças em contexto escolar tem vindo a despertar nas últimas décadas, sobretudo nos vários países da europa, e associando às mudanças políticas consideráveis que o Estado angolano tem vindo a implementar com a Reforma educativa a vigorar mais ou menos a vinte anos, torna-se oportuno refletir sobre a melhoria da qualidade da escola em Angola. Foi desenvolvido um estudo empírico, com a finalidade fundamental de compreender o papel das estruturas de gestão intermédias na liderança e promoção da melhoria da qualidade da escola. Em termos metodológicos, optou-se por um estudo de natureza mista, optando-se pela realização de um estudo de caso, centrado em uma escola do ensino primário e do I ciclo do ensino secundário no Lobito, Angola. Conjugando técnicas de cariz quantitativo e qualitativo, o estudo envolveu a análise documental, a realização de entrevistas e respetiva análise de conteúdo e aplicação e análise estatística de um questionário. O trabalho realizado teve início em agosto de 2019 com a recolha de dados na escola em estudo e contou com a participação de 69 professores, incluindo o diretor da escola. As conclusões mostraram que os gestores intermédios na escola surgem como lideranças efetivas desempenhando um papel preponderante no dinamismo escolar, pois são eles que no dia a dia estão mais perto e presentes na vida dos alunos, como mediadores diretos de um processo de transmissão de valores e conhecimentos para a vida; são os facilitadores na relação entre escola e família; compartilham com os demais professores da turma e classes as conquistas e dificuldades destes na escola e nas famílias.

Objectives: Patients with mild cognitive impairment (MCI) may have difficulties in time perception, which in turn might contribute to some of their symptoms, especially memory deficits. The aim of this study was to evaluate perception of interval length and subjective passage of time in MCI patients as compared to healthy controls. Methods: Fifty-five MCI patients and 57 healthy controls underwent an experimental protocol for time perception on interval length, a questionnaire for the subjective passage of time and a neuropsychological evaluation. Results: MCI patients presented no changes in the perception of interval length. However, for MCI patients, time seemed to pass more slowly than it did for controls. This experience was significantly correlated with memory deficits but not with performance in executive tests, nor with complaints of depression or anxiety. Conclusions: Memory deficits do not affect the perception of interval length, but are associated with alterations in the subjective passage of time.

Background: Cognitive difficulties contribute to patients' disability during migraine attacks and have been overlooked in migraine research. Neuropsychological studies performed during attacks have produced inconsistent findings due to design differences and limitations. Objective: Our objective is to document changes in cognitive performance of migraine patients during migraine attacks with a comprehensive battery of cognitive/behavioral tests, while controlling for potential confounders. Method: A prospective two-period, randomized, cross-over study compared within-subject neuropsychological evaluation in two conditions-during a naturally occurring untreated migraine attack and a headache-free period. Results: Thirty-nine patients with episodic migraine (37 females, average 38 years old) were included and 24 completed the study. Participants performed worse during the attack in the majority of cognitive tests, compared to the headache-free status, and significantly so in word reading speed (p = 0.013), verbal learning (p = 0.01), short-term verbal recall with (p = 0.01) and without (p = 0.013) semantic cueing and delayed recall with (p = 0.003) and without (p = 0.05) semantic cues. Differences found were unrelated to age, gender, literacy, condition order, interval between evaluations, anxiety, pain intensity or duration of the attack. Discussion: Cognitive performance decreases during migraine attacks, especially in reading and processing speed, verbal memory and learning, supporting patients' subjective complaints. These findings suggest the existence of a reversible brain dysfunction during attacks of migraine without aura, which can relate specifically to migraine or be a consequence of acute pain processing by the brain.

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects around 1% of the human population worldwide. RA diagnosis can be difficult as there is no definitive test for its detection. Therefore, the aim of this study was to identify biomarkers that could be used for RA diagnosis. Methods: Sera from a collagen-induced arthritis mouse model were used to select potential biomarkers for RA diagnosis by phage display technology. In silico and in vitro analyses were performed to characterize and validate the selected peptides. Samples were classified into three groups: RA; two other immune-mediated rheumatic diseases (systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS)); and healthy controls (HC). Enzyme-linked immunosorbent assay (ELISA) was carried out to determine antibody levels, and diagnostic parameters were determined by constructing receiver operating characteristic curves. Mass spectrometry and Western blot were performed to identify the putative autoantigen that was mimicked by a highly reactive mimotope. Results: After three rounds of selection, 14 clones were obtained and tested for immunoreactivity analysis against sera from RA and HC groups. The phage-fused peptide with the highest immunoreactivity (M12) was synthesized, and was able to efficiently discriminate RA patients from SLE, AS and HCs (p < 0.0001) by ELISA. The specificity and sensitivity of anti-M12 antibodies for RA diagnosis were 91 % and 84.3 %, respectively. The M12 peptide was identified as one that mimics a predicted antigenic site of the carbonic anhydrase III (CAIII) protein, a ubiquitous biomarker that has been identified in patients with other diseases. Conclusion: M12 is the first peptide associated with the CAIII protein that may be used as an antigen for antibody detection to aid in RA diagnosis with high sensitivity and specificity.

Abnormally expanded DNA repeats are associated with several neurodegenerative diseases. In Friedreich's ataxia (FRDA), expanded GAA repeats in intron 1 of the frataxin gene (FXN) reduce FXN mRNA levels in averaged cell samples through a poorly understood mechanism. By visualizing FXN expression and nuclear localization in single cells, we show that GAA-expanded repeats decrease the number of FXN mRNA molecules, slow transcription, and increase FXN localization at the nuclear lamina (NL). Restoring histone acetylation reverses NL positioning. Expanded GAA-FXN loci in FRDA patient cells show increased NL localization with increased silencing of alleles and reduced transcription from alleles positioned peripherally. We also demonstrate inefficiencies in transcription initiation and elongation from the expanded GAA-FXN locus at single-cell resolution. We suggest that repressive epigenetic modifications at the expanded GAA-FXN locus may lead to NL relocation, where further repression may occur.

Breast cancer diagnosis using radar-based medical MicroWave Imaging (MWI) has been studied in recent years. Realistic numerical and physical models of the breast are needed for simulation and experimental testing of MWI prototypes. We aim to provide the scientific community with an online repository of multiple accurate realistic breast tissue models derived from Magnetic Resonance Imaging (MRI), including benign and malignant tumours. Such models are suitable for 3D printing, leveraging experimental MWI testing. We propose a pre-processing pipeline, which includes image registration, bias field correction, data normalisation, background subtraction, and median filtering. We segmented the fat tissue with the region growing algorithm in fat-weighted Dixon images. Skin, fibroglandular tissue, and the chest wall boundary were segmented from water-weighted Dixon images. Then, we applied a 3D region growing and Hoshen-Kopelman algorithms for tumour segmentation. The developed semi-automatic segmentation procedure is suitable to segment tissues with a varying level of heterogeneity regarding voxel intensity. Two accurate breast models with benign and malignant tumours, with dielectric properties at 3, 6, and 9 GHz frequencies have been made available to the research community. These are suitable for microwave diagnosis, i.e., imaging and classification, and can be easily adapted to other imaging modalities.

Rainfall is considered the most important physical process for landslide triggering in Portugal. It is expected that changes in the precipitation regimes in the region, as a direct consequence of climate change, will have influence in the occurrence of extreme rainfall events that will be more frequently, throughout the century. The aim of this study relied on the assessment of the projected future changes in the extreme precipitation over Portugal mainland and quantifying the correlation between extreme rainfall events and landslide events through Rainfall Triggering Thresholds (RTTs). This methodology was applied for two specific locations within two Portuguese areas of great geomorphological interest. To analyze the past frequency of landslide events, we resorted to the DISASTER database. To evaluate the possible projected changes in the extreme precipitation, we used the Iberia02 dataset and the EURO-CORDEX models’ runs at a 0.11° spatial resolution. It was analyzed the models’ performance to simulate extreme values in the precipitation series. The simulated precipitation relied on RCM-GCM models’ runs, from EURO-CORDEX, and a multimodel ensemble mean. The extreme precipitation assessment relied on the values associated to the highest percentiles, and to the values associated to the RTTs’ percentiles. To evaluate the possible future changes of the precipitation series, both at the most representative percentiles and RTTs’ percentiles, a comparison was made between the simulated values from EURO-CORDEX historical runs (1971–2000) and the simulated values from EURO-CORDEX future runs (2071–2100), considering two concentration scenarios: RCP 4.5 and RCP 8.5. In the models’ performance, the multimodel ensemble mean appeared to be within the best representing models. As for the projected changes in the extreme precipitation for the end of the century, when following the RCP 4.5 scenario, most models projected an increase in the extreme values, whereas, when following the RCP 8.5 scenario, most models projected a decrease in the extreme values.

In the context of the growing global middle class, and the ageing of the baby boomer generation, an increasing number of migrants with accumulated wealth from advanced economies are relocating to economically less developed or more peripheral countries to improve their quality of life. Migration of the middle-classes and the relatively affluent is embedded in the same globalising processes and social transformations in production and processes of accumulation that have reshaped labour migration (Hayes, 2021; Castles, 2010). Privileged mobilities are part of wider migration systems, however, what distinguishes lifestyle migrants from other migrants, who are also in pursuit of a better quality of life, is the ease with which they can relocate due to relative privilege in terms of citizenship and financial or cultural capital.

Background: Currently, assessment of symptoms associated with Parkinson's disease is mainly performed in the clinic. However, these assessments have limitations because they provide only a snapshot of the condition. Methods: The feasibility and usability of an objective, continuous and relatively unobtrusive system (SENSE-PARK System), which consists of wearable sensors (three worn during the day and one worn at night), a smartphone-based App, a balance board and computer software, was tested 24/7 over 12 weeks in a study including 22 PD patients. During the first four weeks of the study, patients did not get feedback about their performance, during the last eight weeks they did. The study included seven clinical visits with standardized interviews, and regular phone contact. The primary outcome was the number of drop-outs during the study. As secondary outcomes, the Post-Study System Usability Questionnaire (PSSUQ), score and information obtained from the standardized interviews were used to evaluate the usability of the system. Results: All patients completed the study. The participants rated the usability of the SENSE-PARK System with a mean score of 2.67 (±0.49) on the PSSUQ. The interviews revealed that most participants liked using the system and appreciated that it signaled changes in their health condition. Conclusions: This 12 week controlled study demonstrates that the acceptance level of PD patients using the SENSE-PARK System as a home-based 24/7 assessment is very good. Particular emphasis should be given to a user-friendly design. Motivation to wear such a system can be increased by providing direct feedback about the individual health condition.

2-Deoxy-2-fluoroglycosyl iodides are privileged glycosyl donors for the stereoselective preparation of 1-Nu-β-fluorosugars, which are useful reagents for chemical site-selective protein glycosylation. Ready access to such β-fluorosugars enables the mild and efficient construction of well-defined fluoroglycoproteins.

As part of environmental health surveillance programs related to solid waste incinerators located near Lisbon and on Madeira Island, human biomonitoring projects have been implemented in Portugal, some of them focused on crosssectional surveys of heavy metals in blood. One of the general aims of these programs is to provide Portuguese data on the extent and pattern of human exposure to the pollutants potentially released in the stack gases from the incinerators, namely heavy metals. The present investigation reports information specifically on blood lead levels of newborn– mother pairs living in the vicinity of the incinerators under study, as well as of statistically similar participants living outside the exposed area. For Lisbon, lead levels determined at the baseline period (T0), as well as three subsequent evaluations of potential specific impacts of the incinerator (T1, T2 and T3) are described in order to investigate spatial and temporal trends of human exposure to lead. Available data for Madeira, namely lead levels in blood from the study population before the incinerator started operation, is also described. For Lisbon, analyses showed a statistically significant decrease of lead concentrations in maternal and umbilical cord blood during the whole monitoring period. Practically ‘‘overt’’ transplacental exposure to lead was observed only in the Lisbon biomonitoring project and for some cross-sectional surveys. Baseline levels for Madeira were the lowest found in all observations already performed in both programs (maternal and umbilical cord mean lead levels of 0.4 mg/dl and 0.3 mg/dl, respectively). No statistical associations have been found between lead levels in blood and age neither for global populations from Lisbon and Madeira nor for specific groups included in the different observational periods.

Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse embryonic stem cell differentiation and following ectopic expression in chick embryonic otic epithelium. Induced HCs (iHCs) express numerous HC-specific markers and exhibit polarized membrane protrusions reminiscent of stereociliary bundles. Transcriptome profiling confirms the progressive establishment of a HC-specific gene signature during in vitro iHC programming. Overall, this work provides a novel approach to achieve robust and highly efficient HC production in vitro, which could be used as a model to study HC development and to drive inner ear HC regeneration.