RCAAP Repository

A vasculite a imunoglobulina A (VIgA), anteriormente designada púrpura de Henoch- Schönlein ou púrpura anafilactóide, é a vasculite sistémica mais prevalente na criança. É uma vasculite imunomediada, com depósitos imunes de IgA individualizados nos pequenos vasos, sobretudo da pele, articulações, trato gastrointestinal e rim. A tétrade clássica de manifestações clínicas inclui: púrpura, artralgia/artrite, dor abdominal e compromisso renal. A nefrite da VIgA (NVIgA) surge num quinto a metade dos casos e, embora menos frequente que as outras manifestações clínicas, surge habitualmente no primeiro mês após o início da doença, e é potencialmente mais grave e mais prevalente na criança mais velha e no adulto. A terapêutica da NVIgA não é consensual, sendo convicção generalizada a necessidade de ensaios multicêntricos, prospetivos, randomizados e controlados. Apresentamos uma revisão da literatura sobre a NVIgA, com enfoque muito especial nas controvérsias e perspetivas atuais do seu tratamento.

Introdução: A retinopatia diabética (RD) é uma manifestação oftalmológica da diabetes mellitus e uma das principais causas de perda de visão à volta do mundo. Com a recente evolução da tecnologia na área da saúde, a inteligência artificial (IA) tem assumido um papel determinante, especialmente neste caso. Assim, foi feita uma revisão sistemática e meta-análise com o propósito de avaliar a capacidade diagnóstica destas IA’s nas vertentes de RD referenciável (RDR), RD com risco de perda de visão (VTDR) e em qualquer tipo de RD. Métodos: Uma pesquisa sistemática da literatura foi realizada na base de dados PubMed. O processo de seleção dos artigos foi feito até à data de 2 de abril de 2021, sendo que foram incluídos somente estudos que fizessem a comparação entre a graduação feita por IA’s e a graduação manual para diagnóstico de retinopatia diabética. Utilizou-se o software Covidence para a triagem e extração dos dados e a ferramenta STROBE para análise da qualidade dos estudos. Resultados: Quinze artigos foram incluídos na revisão sistemática por preencherem os critérios de inclusão. A meta-análise realizada mostrou através do common effect uma sensibilidade e especificidade de 89% e 86% para RDR, respetivamente; 100% e 92% para VTDR, respetivamente; 90% e 73% para qualquer tipo de RD, respetivamente. Não foram calculados valor preditivo positivo e negativo por não haver dados suficientes que permitissem o cálculo. Conclusão: Os achados do nosso estudo demonstraram que as IA’s tiveram alta sensibilidade, bem como especificidade para detetar RD, sobretudo nas categorias mais graves, o que significa que há uma abertura para implementar estes sistemas autónomos como métodos de rastreio auxiliares dos oftalmologistas, tendo como objetivos otimizar fluxos e acelerar o tempo de triagem, sem pôr em causa a precisão no diagnóstico da retinopatia diabética.

A hipófise anterior regula mecanismos tão vastos como o crescimento, o metabolismo ou a reprodução, através da secreção hormonal. As células folículo-estreladas (CFE), células não endócrinas situadas entre as células produtoras de hormonas da hipófise anterior, têm uma função ainda pouco conhecida. Apesar de tudo, com a sua organização em rede, parecem ter um importante papel na regulação e manutenção da população de células hormonais. Neste trabalho, o primeiro do género de que há registo, 33 hipófises de três grupos de ratinhos (18 wild type [WT], 11 geneticamente obesos [OB] e 4 sob uma dieta rica em ácidos gordos [HFD]) foram analisadas de forma a avaliar se existiria alguma relação entre o número de CFE e as alterações do metabolismo basal de cada grupo de ratinhos. Recorreu-se à marcação imunohistoquímica pela proteína S-100, a técnicas de imunofluorescência e ao software Image-J para se conseguir calcular a percentagem de CFE presentes em cada amostra. Chegou-se à conclusão de que, apesar de não se notarem diferenças significativas entre os ratinhos WT e OB, o grupo de ratinhos HFD teria uma percentagem de CFE significativamente superior aos outros dois grupos. Isto pode sugerir uma relação ainda desconhecida entre a dieta, em concreto uma dieta rica em ácidos gordos, e a apresentação de CFE na hipófise anterior. Os mecanismos e consequências fisiológicas subjacentes a esta alteração deverão, por isso, ser estudados, por forma a obter um maior esclarecimento da temática.

The concentration of lead in liver and kidneys of Wistar rats, fed with lead since fetal period in relation to their age and to a control group, was determined. A group of rats was exposed to lead acetate (n=30) in drinking water and the other group was exposed to normal water (n=20). Samples were collected from rats aging between 1 and 11 months and were analyzed by Energy Dispersive X-ray Fluorescence (EDXRF) without any chemical preparation. The EDXRF results were assessed by the PIXE (Proton Induced X-ray Emission) technique. The formaldehyde used to preserve the samples was also analyzed by ETAAS (Electro-Thermal Atomic Absorption Spectrometry) in order to verify if there was any loss of lead from the samples to the formaldehyde. We found that the loss was not significant (<2%). Concerning the mean values of the lead concentration measured in the contaminated soft tissues, in liver they range from 6 to 22μgg(-1), and in kidneys from 44 to 79μgg(-1). The control rats show, in general, values below the EDXRF detection limit (2μgg(-1)). The ratio kidney/liver ranges from 2 to 10 and is strongly positively correlated with the age of the animals. A Spearman correlation matrix to investigate the correlation between elemental concentrations and the dependence of these concentrations with age showed that there is a strong positive correlation with age for lead in the liver but not in the kidney. The correlation matrix showed also that the concentration of lead in these two soft tissues is not correlated. The lead accumulation in liver is made by different plateaus that strongly decrease with age. It was verified the existence of two levels of accumulation in kidney, not very highlighted, which might be indicative of a maximum accumulation level for lead in kidney.

The accumulation of lead in several bones of Wistar rats with time was determined and compared for the different types of bones. Two groups were studied: a control group (n = 20), not exposed to lead and a contaminated group (n = 30), exposed to lead from birth, first indirectly through mother's milk, and then directly through a diet containing lead acetate in drinking water (0.2%). Rats age ranged from 1 to 11 months, with approximately 1 month intervals and each of the collections had 3 contaminated rats and 2 control rats. Iliac, femur, tibia-fibula and skull have been analysed by Energy Dispersive X-ray Fluorescence Technique (EDXRF). Samples of formaldehyde used to preserve the bone tissues were also analysed by Electrothermal Atomic Absorption (ETAAS), showing that there was no significant loss of lead from the tissue to the preservative. The bones mean lead concentration of exposed rats range from 100 to 300 μg g(-1) while control rats never exceeded 10 μg g(-1). Mean bone lead concentrations were compared and the concentrations were higher in iliac, femur and tibia-fibula and after that skull. However, of all the concentrations in the different collections, only those in the skull were statistically significantly different (p < 0.05) from the other types of bones. Analysis of a radar chart also allowed us to say that these differences tend to diminish with age. The Spearman correlation test applied to mean lead concentrations showed strong and very strong positive correlations between all different types of bones. This test also showed that mean lead concentrations in bones are negatively correlated with the age of the animals. This correlation is strong in iliac and femur and very strong in tibia-fibula and skull. It was also shown that the decrease of lead accumulation with age is made by three plateaus of accumulation, which coincide, in all analysed bones, between 2nd-3rd and 9th-10th months.

Vagal activity is thought to influence atrial electrophysiological properties and play a role in the initiation and maintenance of atrial fibrillation (AF). We evaluated the effects of acute vagal stimulation on atrial conduction, refractoriness of atrial and pulmonary veins (PVs) and inducibility of AF. An open-chest epicardial approach was performed in New Zealand White rabbits with preserved autonomic innervation. Atrial electrograms were obtained with four unipolar electrodes placed epicardially along the atria (n = 22) and an electrode adapted to the proximal left PV (n = 10). The cervical vagus nerve was stimulated with bipolar platinum electrodes (20 Hz). Epicardial activation was recorded in sinus rhythm, and effective refractory periods (ERPs), dispersion of refractoriness and conduction times from high-lateral right atrium (RA) to high-lateral left atrium (LA) and PVs assessed at baseline and during vagal stimulation. Burst pacing (50 Hz, 10 s), alone or combined with vagal stimulation, was applied to the right (RAA) and left atrial appendage (LAA) and PVs to induce AF. At baseline, ERPs were lower in PVs than in LA and LAA, but did not differ significantly from RA and RAA, and there was a significant delay in the conduction time from RA to PVs compared with the activation time from RA to LA (P < 0.01). During vagal stimulation, ERP decreased significantly at all sites, without significant differences in the dispersion of refractoriness, and the atrial conduction times changed from 39 ± 19 to 49 ± 9 ms (RA to PVs; n.s.) and from 14 ± 7 to 28 ± 12 ms (RA to LA; P = 0.01). Induction of AF was reproducible in 50% of cases with 50 Hz and in 82% with 50 Hz combined with vagal stimulation (P < 0.05). During vagal stimulation, AF cycle length decreased at all sites, and AF duration changed from 1.0 ± 0.9 to 14.0 ± 10.0 s (P < 0.01), with documentation of PV tachycardia in three cases. In 70% of the animals, AF ceased immediately after interruption of vagal stimulation. We conclude that in the intact rabbit heart, vagal activity prolongs interatrial conduction and shortens atrial and PV ERP, contributing to the vulnerability to the induction and maintenance of AF. This model may be useful in the assessment of the autonomic influence in the mechanisms underlying AF.

The perception of landscape and its transformation underpins the process of socio-ecological awareness that is essential to a healthy relationship between Humans and Nature. One of the great challenges to contemporary and future society is the vital need to increase knowledge and awareness of the development model that has led us to the global ecological crisis that we face today. We know that resources may become scarce if we continue to consume them at the current rate, especially if the rise in atmospheric temperature exceeds certain limits. The landscape reflects this economic model and the decisions that are taken on the territory. Different expressions may be used depending on the scale and intensity of the transformation that has occurred as the landscape is a resource that is essential not only to the development of economic activities but also to the qualification of the territory and the well-being of the population (Cassatella and Peano, 2011). In Portugal, the result of two critical trends can be observed in the landscape - the depopulation of rural areas with the consequent concentration of population in urban settlements influenced by the coastline, and the inevitable simplification of the agricultural and forest cultural mosaics.

Este documento descreve o trabalho realizado no âmbito da disciplina de Projecto em Engenharia Informática do Mestrado em Engenharia Informática da Faculdade de Ciências da Universidade de Lisboa. Este projecto, desenvolvido na GEDI S.A., teve como principal objectivo criar uma ferramenta que auxilie as organizações na tomada de decisões de maneira a melhorar o seu desempenho no negócio. A técnica utilizada para se conseguir isto denomina-se BPM (Business Performance Management). É uma técnica que se pode considerar uma evolução dos sistemas de BI (Business Intelligence) convencionais. O projecto foi desenvolvido utilizando um conjunto de frameworks open source, sendo a linguagem de programação base o JAVA, na plataforma J2EE, e para as camadas de interface, negócio e dados: Struts ou JavaServer Pages, Spring e Hibernate correspondentemente. Para auxiliar no desenho de gráficos foi usada a ferramenta FusionCharts em conjunto com o Java. Foi ainda utilizada a tecnologia JavaServer Faces para a parte de forecasting do projecto. A ferramenta desenvolvida funciona de forma integrada com o sistema SIAG-AP (Sistema Integrado de Apoio à Gestão para a Administração Pública) desenvolvido pela GEDI.

Neurocardiogenic syncope (NCS) is a common clinical entity resulting from an excessive reflex autonomic response, particularly during orthostatism. Treatment options are controversial and of limited effectiveness. Tilt training (TT) is a promising option to treat these patients. However, its mechanism of action and clinical impact remain unclear. Objective: To characterize hemodynamic and autonomic responses during a TT program in patients with NCS refractory to conventional measures. Methods: We studied 28 patients (50% male, mean age 41±14 years) without structural heart disease, with NCS documented by tilt testing. The TT program included 9 tilt sessions (3 times a week, 30 min) (60° - 6 sessions, 70° - 3 sessions), under ECG and blood pressure monitoring combined with home orthostatic self-training and 10° head-up during sleep. Systolic volume, cardiac output, total peripheral resistance, baroreflex sensitivity and heart-rate variability were computed. Patients were reassessed at 1 month and every 6 months for a maximum of 36 months (24±12 months). Results: Over the course of the TT program there was a significant increase in total peripheral resistance (1485±225 vs. 1591±187 dyn·s·cm(-5), p<0.05), with a decrease in standard deviation (206±60 vs. 150±42, p<0.05). During follow-up, syncope recurred in five patients (19%), with a significant reduction in the number of episodes (4.0±3.2/patient in the 12 months before TT vs. 1.4±0.8/patient post-TT, p<0.05). Conclusion: In refractory NCS, TT may be an effective therapeutic option, with long-term benefits. These results appear to be due to an increase in vasoconstrictor reserve combined with a reduction in its variance.

Abstract: During and in the aftermath of the COVID-19 pandemic, several works reflected on young people’s physical and psychological health. The Dual Factor Model, which we refer to as the quadripartite model, is useful for understanding children’s and adolescents’ psychological health and differentiating them regarding their attitude toward the effects of the COVID-19 pandemic. In this investigation, students from the fifth to twelfth year of schooling enrolled in the DGEEC study “Psychological Health and Wellbeing in Portuguese schools” were considered. Four groups were created based on life satisfaction (low or high) and psychological distress (with or without symptoms). The study included 4444 students (M = 13.39 years ± 2.41), of whom 47.8% were male. Of the participants, 27.2% were in the second cycle of primary education, and 72.8% were in lower and upper secondary education. Differences in gender and education level (as a proxy for age) were observed. Additionally, when considering students’ perceptions of changes in their lives following the COVID-19 pandemic (stayed the same, became worse, became better), these three groups were compared concerning personal and contextual variables, revealing significant differences at both the individual and contextual levels. Finally, the study discusses the influence of education and health professionals and the need for friendly public policies.

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

In an unprecedented scenario, much of the research and interventions during the COVID-19 pandemic, which focused on young people, found themselves suspended. (1) Background: The goals of this project were to investigate (Study 1) social participation and positive development among young people in Cascais, Portugal, and to investigate (Study 2-a case study) the implementation of a program promoting active citizenship, social participation, and social entrepreneurship. At the same time, it was intended to constitute a resource and strategy to diminish the social alienation exacerbated by the pandemic. (2) Methods: SPSS v.26 software was used to analyze quantitative data from questionnaires used in the study of social participation, as well as the pre- and post-test impacts, and MAXQDA 2020 software was used to analyze qualitative data from YouTube discussions about youth needs and strategies for their problems, as well as from focus groups. (3) Results: In S1, it was evident that young people’s expectations of participation in the community were not defined and that their expected participation in the community was of a weekly nature. They considered themselves to have a good sense of belonging to the community or group and had reasonable social self-efficacy. Girls showed higher scores in Expectations of Community Participation and Active Participation. In their positive development, they did not have a defined evaluation of their competence, but their connection with others was evaluated as good. Boys showed higher levels of Competence. They said that every week they make 1 h of their day available to help others, and they did not frequently report feelings of social alienation. In S2, the evaluation of the impact of the project generally showed an improvement in the action research skills of the participants. At the end, six projects were proposed. In the analysis of the participants’ voices, the themes related to Substance Use, Social Capital, and Love and Sexuality stood out with higher participation and lower participation in the themes of Diversity, Culture and Housing. (4) Conclusions: The results suggest a need to encourage social participation, active citizenship, and entrepreneurship, along with their knowledge and skills for action. The promotion of debate and knowledge on issues related to young people’s lives seems to be a priority, especially issues related to Diversity, Culture and Housing. The Dream Teens model may prove to be an important strategy in this work, suggesting that this project may constitute a relevant model for future work.

Introduction and objectives: Asthma is a chronic and heterogeneous disease that affects people of all ages and has a high estimated increase in prevalence worldwide. Asthma control represents a main goal in the disease management. International studies revealed low levels of disease control resulting in a significant burden for healthcare systems, not only in terms of quality of life, but also in terms of health costs. Modifiable and non-modifiable factors have been identified as relating to poor asthma control level. In this study we evaluated the distribution of asthma control levels in Portuguese adult population and examine the determinants associated with uncontrolled asthma. Materials and methods: Using a similar methodology to the one employed in the Asthma Insights and Reality in Europe (AIRE) survey, 327 active asthmatic patients were identified by random phone number and completed a questionnaire during 2011 to 2012. Asthma control was assessed by the evaluation of GINA based symptom control, by Asthma Control Test.äó (ACT) and by self-perception of control. To examine the relationship between uncontrolled asthma and its determinants, univariate logistic regression analysis, sequential multivariable regression and population attributable risk percentage were determinate. Results: 35.2% active asthmatic patients had uncontrolled asthma, 64.8% partially controlled and none of the individuals had total control of asthma assessed by ACT test. Factors significantly associated with poor asthma control scores were: age (OR 1.02 per year of age; 95% CI: 1.01.Çô1.03), female sex (OR 1.87; 95% CI: 1.15.Çô3.04), educational level (OR 0.5; 95% CI: 0.28.Çô0.89 at high school level or over), occupation (OR 4.92; 95% CI: 2.12.Çô11.42 if looking for a first job or unemployed) (OR 2.51; 95% CI: 1.35.Çô4.65 if being retired), income (OR 0.23; 95% CI: 0.07.Çô0.72 if >619 euros), BMI (OR 1.09 per BMI unit; 95% CI: 1.03.Çô1.14), having rhinitis symptoms (OR 4.40; 95% CI: 2.56.Çô7.58) and using inhaled corticosteroids (OR 0.44; 95%CI: 0.24.Çô0.82 if used in the past or never used). Looking for a first job or being unemployed, BMI and having rhinitis symptoms remained significant after multivariate adjustments. Conclusions: Uncontrolled asthma was associated with several determinants. Their identification can contribute to improve asthma care both from clinical and from public health perspectives.

Purpose: A clinicopathological classification has been designed to predict recurrence/progression in patients with pituitary adenomas (PAs). We aimed to study its usefulness in predicting PAs that will have a challenging disease course and may require more often complex multimodal and multiple therapeutic approaches. Methods: Retrospective analysis of 129 patients with PAs operated in our institution between 2001 and 2020 (84 non-clinically functioning PAs, 32 acromegaly, 9 Cushing's disease, 2 prolactinomas and 2 thyrotropinomas). Grading was based on invasion and proliferation: 1a (non-invasive, non-proliferative; n = 59), 1b (non-invasive, proliferative; n = 17), 2a (invasive, non-proliferative; n = 38), and 2b (invasive, proliferative; n = 15). Results: Of the 129 patients, 68 (52.7%) were females, and the mean age at diagnosis was 53.7 ± 15.4 years. The mean follow-up duration was 93.1 ± 61.8 months. Grade 2b PAs when compared to other grades (2b-2a-1b-1a) had significantly higher rates of persistent tumor remnant within 1-year after operation (93-78-18-30%; p < 0.001), active disease at last follow-up (40-27-12-10%; p = 0.004), re-operation (27-16-0-5%; p = 0.023), irradiation (53-38-12-7%; p < 0.001), multimodal treatment (67-49-18-25%; p = 0.003), multiple treatment (33-27-6-9%; p = 0.017). Patients with grade 2b PAs also required a higher mean number of treatments (2.6-2.1-1.2-1.4; p < 0.001). Conclusions: This clinicopathological classification appears to be a useful grading system to identify PAs that may be more refractory and more often require complex multimodal and multiple therapeutic approaches. Invasive PAs, especially grade 2b tumors, may be more likely to need complex treatment approach, including radiotherapy, and may display higher rates of active disease at last follow-up, despite receiving higher number of treatments.

Background: Acute Myocardial Infarction (AMI) is the leading cause of death in Portugal and globally. The present investigation created a model based on machine learning for predictive analysis of mortality in patients with AMI upon admission, using different variables to analyse their impact on predictive models. Methods: Three experiments were built for mortality in AMI in a Portuguese hospital between 2013 and 2015 using various machine learning techniques. The three experiments differed in the number and type of variables used. We used a discharged patients' episodes database, including administrative data, laboratory data, and cardiac and physiologic test results, whose primary diagnosis was AMI. Results: Results show that for Experiment 1, Stochastic Gradient Descent was more suitable than the other classification models, with a classification accuracy of 80%, a recall of 77%, and a discriminatory capacity with an AUC of 79%. Adding new variables to the models increased AUC in Experiment 2 to 81% for the Support Vector Machine method. In Experiment 3, we obtained an AUC, in Stochastic Gradient Descent, of 88% and a recall of 80%. These results were obtained when applying feature selection and the SMOTE technique to overcome imbalanced data. Conclusions: Our results show that the introduction of new variables, namely laboratory data, impacts the performance of the methods, reinforcing the premise that no single approach is adapted to all situations regarding AMI mortality prediction. Instead, they must be selected, considering the context and the information available. Integrating Artificial Intelligence (AI) and machine learning with clinical decision-making can transform care, making clinical practice more efficient, faster, personalised, and effective. AI emerges as an alternative to traditional models since it has the potential to explore large amounts of information automatically and systematically.

Introdução: A importância da Microbiota Cervicovaginal na proteção de infeções (como o HPV) encontra-se bem estabelecida, nomeadamente através dos Lactobacillus spp., tal como o mecanismo através do qual o HPV conduz à Neoplasia Cervical. Contudo, não é possível classificar o HPV como um carcinogéneo completo. Desta forma, a importância de explorar a disbiose da MCV com a intenção de decifrar esta interação com o HPV, toma maior relevância. Objectivos: 1) Comparação da composição do MCV de mulheres com e sem HPV e de mulheres com ASCUS e LSIL; 2) Caraterização das citocinas presentes no microambiente vaginal; 3) Avaliação dos índices do hemograma como biomarcadores de prognóstico; 4) Correlação entre MCV, genótipos de HPV e citocinas. Metodologia: Trata-se de um estudo retrospetivo, observacional, multicêntrico e transversal. A análise da MCV realizou-se através do isolamento do ARN bacteriano 16s, e análise numa plataforma de NGS. As concentrações citocinas da MCV foram obtidas através de plataforma Multiplex. A análise estatística foi realizada em SPSS v 26.0. Um α de 0,05 foi considerado estatisticamente significativo. Resultados: Realçando o cerne do estudo, verificou-se que MCV do tipo CST III e CST IV influenciam o surgimento de lesões cervicais. Observou-se que o INL impacta o prognóstico de ASCUS. Dentro da MCV, os Lactobacillus impedem o crescimento de espécies do CST IV, enquanto as últimas expressam relações simbióticas entre si e apresentam afinidade com genótipos específicos de HPV. Por fim, a RANTES eleva-se significativamente perante infeções cervicovaginais. Conclusão: A importância da utilização do perfil de citocinas e da MCV é realçada na hipótese de prevenção do desenvolvimento de NC tal como na sua utilização como biomarcador de prognóstico. Estes conhecimentos permitem dar mais um passo na direção da medicina personalizada.

A miocardiopatia hipertrófica com aneurisma apical é uma variante da miocardiopatia hipertrófica com maior risco de eventos adversos, principalmente de natureza arrítmica, e morte súbita, que se julga estarem relacionados com a existência de uma dilatação apical discinética de paredes finas ao nível do ventrículo esquerdo. Esta formação aneurismática confere o substrato para mecanismos de reentrada, responsáveis pela ocorrência de taquicardias ventriculares monomórficas recorrentes com grande peso na morbilidade e mortalidade dos indivíduos que apresentam esta doença. Desta forma, esta revisão pretende sumarizar a clínica, diagnóstico e tratamento desta variante, de maneira a atuar de forma precoce e correta nos desfechos possíveis da mesma. Aborda-se, por isso, para além do tratamento já preconizado para a miocardiopatia hipertrófica no geral, a utilização da técnica de ablação por cateter de radiofrequência para impedir o ressurgimento dos eventos arrítmicos relacionados com o aneurisma apical.

A sociedade portuguesa pós-restauração viu-se confrontada com um forte debate sobre os diferentes modelos de poder político e o modo como este deveria ser exercido pela Coroa. Determinadas facções defendiam uma concepção política mais tradicional, com maior peso dos conselhos e tribunais e que implicava mecanismos de inclusão e participação da nobreza no processo de decisão política. Contrariando esta ideia surgem os partidários de um outro paradigma, estritamente ligado à Monarquia Católica de Filipe IV, onde o processo decisório era partilhado entre um conjunto reduzido de personalidades e onde as estruturas maiores, como os conselhos, eram substituídas por outras mais pequenas como as juntas, ou até mesmo com recurso ao valimento, que, ao contrário do primeiro modelo, implicava mecanismos de exclusão. A primeira fórmula, mais tradicional, estava em conformidade com uma das principais fundamentações do movimento de Dezembro de 1640: restauração das principais instituições políticas do Reino, num modelo governativo considerado tipicamente português, que desse modo poderia assegurar o melhor governo dos vassalos. O Conselho de Estado, principal órgão político da Monarquia portuguesa, constitui-se como um espaço privilegiado para a observação destes arquétipos em confronto e esteve permanentemente no centro deste debate. Deste modo, o nosso objectivo com este estudo será analisar o papel que o Conselho de Estado desempenhou no seio deste debate e a projecção que teve durante estes anos, no exercício dos diferentes modelos políticos.

The success of personalized medicine depends on the discovery of biomarkers that allow oncologists to identify patients that will benefit from a particular targeted drug. Molecular tests are mostly performed using tumor samples, which may not be representative of the tumor's temporal and spatial heterogeneity. Liquid biopsies, and particularly the analysis of circulating tumor DNA, are emerging as an interesting means for diagnosis, prognosis, and predictive biomarker discovery. In this study, the amplification refractory mutation system (ARMS) coupled with high-resolution melting analysis (HRMA) was developed for detecting two of the most relevant KRAS mutations in codon 12. After optimization with commercial cancer cell lines, KRAS mutation screening was validated in tumor and plasma samples collected from patients with pancreatic ductal adenocarcinoma (PDAC), and the results were compared to those obtained by Sanger sequencing (SS) and droplet digital polymerase chain reaction (ddPCR). The developed ARMS-HRMA methodology stands out for its simplicity and reduced time to result when compared to both SS and ddPCR but showing high sensitivity and specificity for the detection of mutations in tumor and plasma samples. In fact, ARMS-HRMA scored 3 more mutations compared to SS (tumor samples T6, T7, and T12) and one more compared to ddPCR (tumor sample T7) in DNA extracted from tumors. For ctDNA from plasma samples, insufficient genetic material prevented the screening of all samples. Still, ARMS-HRMA allowed for scoring more mutations in comparison to SS and 1 more mutation in comparison to ddPCR (plasma sample P7). We propose that ARMS-HRMA might be used as a sensitive, specific, and simple method for the screening of low-level mutations in liquid biopsies, suitable for improving diagnosis and prognosis schemes.

Resistance training has been shown to acutely increase arterial stiffness (AS), while endurance training appears to decrease AS. However, the findings are from studies in apparently healthy subjects and have limited applicability to patients at low and high cardiovascular risk, for whom combined exercise is recommended. We compared the time course of changes in local and regional indices of AS in response to high-volume combined endurance training (CET) and high-volume combined resistance training (CRT) in patients with coronary artery disease (CAD) and heart failure (HF). We studied 20 men with CAD and HF (10 each) aged 68.3 ± 9.6 years. AS was measured by pulse wave velocity (PWV), and brachial and central blood pressure (BP) were determined after 15 min of rest and 5 and 15 min after the exercise session. All patients completed two sessions on nonconsecutive days. A protocol by time interaction effect was observed for carotid (η2 = 0.21, p = 0.02), aortic (η2 = 0.60, p < 0.001), and femoral (η2 = 0.46, p = 0.01) PWV after CET and CRT, suggesting that PWV decreased after CET and increased after CRT. Decreases in the brachial and central variables of BP across time points were observed in both protocols. CET decreased whereas CRT increased carotid, aortic, and femoral PWV at 15 min after exercise in patients with CAD and HF.