RCAAP Repository

This essay focuses on the biography of Britannicus, son of Claudius and Valeria Messalina, considering particularly the information transmitted by Tacitus in the Annales. Tacitus’ work is also the only source that realizes that Britannicus would have been sexually assaulted by Nero, his brother by adoption, brother-in-law and rival as far as power was concerned. Thus, we also intend to analyse the reference to the stuprum of the young prince and its meaning within the historiography of Tacitus.

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 interessantes para a prática clínica, com base na melhor evidência científica. 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).

Objectives: To investigate the cross-sectional and prospective associations of lifestyle risk behaviors clustering with elevated depressive symptoms and to explore synergic prospective associations of different combinations of lifestyle risk behaviors with subsequent depressive symptoms. Study design: Prospective cohort study. Data on 31,190 middle-aged and older adults from waves 4 (2011) and 6 (2015) of the Survey of Health, Ageing and Retirement in Europe (SHARE) were used. Main outcome measures: Elevated depressive symptoms were estimated using the EURO-D 12-item scale. Lifestyle risk behaviors composing the cluster included physical inactivity, inadequate consumption of fruit and/or vegetables, binge drinking, and tobacco smoking. Gender, age group, education, place of residence, country, number of chronic diseases and body mass index were considered as confounders. Results: With the exception of binge drinking, all lifestyle risk behaviors were associated with higher odds of elevated depressive symptoms in cross-sectional and prospective analyses. The clustering of unhealthy lifestyle behaviors was cross-sectionally associated with elevated depressive symptoms and the clustering of two [odds ratio [OR]: 1.39; 95%CI: 1.28-1.51) and three or four (OR: 1.60; 95%CI: 1.38-1.85) were prospectively associated with elevated depressive symptoms. There were no interactions between the pairs of behaviors in the association with later elevated depressive symptoms. Conclusions: Our findings support the need for interventions integrating multiple health behaviors to prevent elevated depressive symptoms among middle-aged and older adults.

Motivation can be broadly defined as what moves people to act. Low motivation is a frequently reported factor for the reduced physical activity (PA) levels observed in patients with chronic obstructive pulmonary disease (COPD). This study assessed patients' motives to be physically active, according to three pulmonary rehabilitation (PR) participation groups (Never PR, Previous PR and Current PR) and explored whether these motives were related to the PA levels and clinical characteristics. The motives to be physically active were assessed with the Exercise Motivation Inventory-2 (EMI-2, 14 motivational factors, five dimensions) and PA with accelerometry (PA groups: <5000 steps/day vs. ≥5000 steps/day). The clinical variables included symptoms, impact of the disease, exercise capacity and comorbidities. Ninety-two patients (67.4 ± 8.1 years, 82.6% male, forced expiratory volume in 1s (FEV1) 48.3 ± 18.9% predicted; 30.4% Never PR, 51% Previous PR and 18.5% Current PR) participated. The motivational dimensions related to health/fitness presented the highest scores (3.8 ± 1.1; 3.4 ± 1.3). The motives to be active were not significantly different between PA groups (p > 0.05) but having less symptoms and ≥two comorbidities were associated with higher scores in psychological/health and body-related motives, respectively (p < 0.05). The findings may encourage health professionals to actively explore with patients their motives to be physically active to individualise PA promotion.

The Sodium/Iodide Symporter (NIS) is responsible for the active transport of iodide into thyroid follicular cells. Differentiated thyroid carcinomas (DTCs) usually preserve the functional expression of NIS, allowing the use of radioactive iodine (RAI) as the treatment of choice for metastatic disease. However, a significant proportion of patients with advanced forms of TC become refractory to RAI therapy and no effective therapeutic alternatives are available. Impaired iodide uptake is mainly caused by the defective functional expression of NIS, and this has been associated with several pathways linked to malignant transformation. MAPK signaling has emerged as one of the main pathways implicated in thyroid tumorigenesis, and its overactivation has been associated with the downregulation of NIS expression. Thus, several strategies have been developed to target the MAPK pathway attempting to increase iodide uptake in refractory DTC. However, MAPK inhibitors have had only partial success in restoring NIS expression and, in most cases, it remained insufficient to allow effective treatment with RAI. In a previous work, we have shown that the activity of the small GTPase RAC1 has a positive impact on TSH-induced NIS expression and iodide uptake in thyroid cells. RAC1 is a downstream effector of NRAS, but not of BRAF. Therefore, we hypothesized that the positive regulation induced by RAC1 on NIS could be a relevant signaling cue in the mechanism underlying the differential response to MEK inhibitors, observed between NRAS- and BRAF-mutant tumors. In the present study, we found that the recovery of NIS expression induced through MAPK pathway inhibition can be enhanced by potentiating RAC1 activity in thyroid cell systems. The negative impact on NIS expression induced by the MAPK-activating alterations, NRAS Q61R and BRAF V600E, was partially reversed by the presence of the MEK 1/2 inhibitors AZD6244 and CH5126766. Notably, the inhibition of RAC1 signaling partially blocked the positive impact of MEK inhibition on NIS expression in NRAS Q61R cells. Conversely, the presence of active RAC1 considerably improved the rescue of NIS expression in BRAF V600E thyroid cells treated with MEK inhibitors. Overall, our data support an important role for RAC1 signaling in enhancing MAPK inhibition in the context of RAI therapy in DTC, opening new opportunities for therapeutic intervention.

Background: In patients with venous thromboembolism (VTE), bleeding risk should be carefully assessed but none of the available risk scores is currently recommended. The aim of this study was to systematically evaluate the performance of bleeding scores in patients with VTE focusing on high-risk patients. Methods: Longitudinal studies were searched in Medline and Cochrane Library, as well as reviews and references of retrieved articles. Studies were identified, data were extracted, and reporting quality was evaluated. We determined the sensitivity, specificity, positive likelihood ratio (LR+), and diagnostic odds ratio (DOR) of the 'high risk' category of each bleeding score. Random effects meta-analysis was performed in order to derive the central estimates and 95% confidence intervals (95% CI). Results: Twenty-one studies and ten bleeding scores fulfilled the inclusion criteria. VTE-BLEED showed the highest sensitivity but the second-lowest specificity (Se 76%; Sp 61%), followed by ACCP (Se 59%; Sp 57%). The remaining scores had high specificity (> 80%) but a low sensitivity (< 20%). HEMORR2HAGES and Niewenhuis score showed the best performance regarding LR+ that was 2.67 and 5.91, respectively. Regarding DOR, the Niewenhuis score and VTE-BLEED were the best performers with 9.04; 95% CI 3.87-21.09 and 4.94 95% CI 2.66-9.09, respectively. In a cohort with patients predominantly treated with direct oral anticoagulants (DOACs), VTE-BLEED had the highest sensitivity (Se 77%; Sp 60%). Conclusions: Overall, the majority of the risk scores showed a moderate ability to forecast major bleeding events, with the VTE-BLEED as the most sensitive in patients treated with DOACs.

No contexto da cultura escolar, cada experiência e cada sucesso são marcados por uma transformação e por uma singularidade. As práticas educativas caracterizam-se por uma normatividade estruturada através de uma gramática, tendendo para hábitos e traduzindo-se em rotinas. As práticas são mediações da cultura escolar. Após uma explanação teórica e de contextualização na instituição escolar e na cultura escrita, aborda-se a caligrafia como prática de normatividade.

This article positions collective renewable energy prosumerism as a social movement that engages in energy system transformation. Collective renewable energy prosumer initiatives engage in ‘prefigurative’ work through their discursive framings (ways of thinking), their activities (ways of doing) and their understanding and enactment of social relations (ways of organising). The core of this article is a comparative analysis of the prefigurative work of 13 collective prosumers from 7 European countries (Belgium, Croatia, Germany, Italy, Netherlands, Portugal, United Kingdom). The article discusses their contributions to energy system transformation, including renewable energy production, different mechanisms for involving citizens, local value creation, and the degree of desired and actual collaboration and networking within broader prosumer ecosystems. We then discuss these contributions against societal discourses and expectations towards prosumerism, such as energy democracy, energy justice, and environmental sustainability and decarbonisation. This reveals three tensions: 1) a focus on decarbonisation but not on broader environmental problems, 2) the involvement of certain people and not of others, and 3) the building of prosumer eco-systems while ignoring incumbency. Future research avenues are formulated to conclude the article

Portuguese-speaking countries are at different levels in the process of promoting environmental education and sustainability. In recognition of the political and cultural ties within a considerable diversity of socio-economic conditions, a pioneering study was developed in 2017 to map and establish a diagnostic of Environmental Education’s (EE) realities and “sustainability norms legislation” in the Lusophone nations. Three years later, the EE2CPLP survey, implemented in 2020, builds upon and streamlines the first edition, considering the current context marked by Agenda 2030 and the impacts and concerns regarding the COVID-19 pandemic. Thus, the survey was divided into three main sections: (1) Contexts and EE approaches in the CPLP countries; (2) Place and role of children and youth in the field of EE and (3) Coronavirus pandemic environment, against the backdrop of Agenda 2030. In the following chapter, we will address EE’s cross-cutting nature, its selective traditions (i.e., positivist, normative, and pluralist) and its role for sustainable development and the 2030 Agenda. Looking for the perspective of stakeholders and experts in Environmental Education (EE) and sustainability, we will assess the perceived impact of the current health crisis, which compounds the climate crisis, exacerbating the socio-economic issues within Portuguese-speaking countries.

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Background: Bipolar disorder is a chronic and often debilitating illness. Current treatment options (both pharmaco- and psychotherapy) have shown efficacy, but for many leave a shortfall in recovery. Advances in the understanding of the pathophysiology of bipolar disorder suggest that interventions that target mitochondrial dysfunction may provide a therapeutic benefit. Methods: This review explores the current and growing theoretical rationale as well as existing preclinical and clinical data for those therapies aiming to target the mitochondrion in bipolar disorder. A Clinicaltrials.gov and ANZCTR search was conducted for complete and ongoing trials on mitochondrial agents used in psychiatric disorders. A PubMed search was also conducted for literature published between January 1981 and July 2017. Systematic reviews, randomized controlled trials, observational studies, case series, and animal studies with an emphasis on agents affecting mitochondrial function and its role in bipolar disorder were included. The search was augmented by manually searching the references of key papers and related literature. The results were presented as a narrative review. Results: Mitochondrial agents offer new horizons in mood disorder treatment. While some negative effects have been reported, most compounds are overall well tolerated and have generally benign side-effect profiles. Conclusions: The study of neuroinflammation, neurodegeneration, and mitochondrial function has contributed the understanding of bipolar disorder's pathophysiology. Agents targeting these pathways could be a potential therapeutic strategy. Future directions include identification of novel candidate mitochondrial modulators as well as rigorous and well-powered clinical trials.

Traça-se um quadro evolutivo da legislação e da realidade escolar portuguesas, tomando como principal referência o Poder Local e muito particularmente o Município. Problematiza-se e documenta-se o conceito de Município Pedagógico.

We investigated the genetic role of sortilin (SORT1) in frontotemporal dementia (FTD). SORT1 is the neuronal receptor for granulin, encoded by the progranulin gene (GRN), a major causal gene for inherited FTD. In Belgian cohorts of 636 FTD patients and 1066 unaffected control individuals, we identified 5 patient-only nonsynonymous rare variants in SORT1. Rare variant burden analysis showed a significant increase in rare coding variants in patients compared to control individuals (p = 0.04), particularly in the β-propeller domain (p = 0.04), with 2 rare variants located in the predicted binding site for GRN (p = 0.001). We extended these observations by analyzing 3 independent patient/control cohorts sampled in Spain, Italy, and Portugal by partners of the European Early-Onset Dementia Consortium, together with 1155 FTD patients and 1161 control persons. An additional 7 patient-only nonsynonymous variants were observed in SORT1 in European patients. Meta-analysis of the rare nonsynonymous variants in the Belgian and European patient/control cohorts revealed a significant enrichment in FTD patients (p = 0.006), establishing SORT1 as a genetic risk factor for FTD.

Vernet syndrome is a unilateral palsy of glossopharyngeal, vagus, and accessory nerves. Varicella zoster virus (VZV) infection has rarely been described as a possible cause. A 76-year-old man presented with 1-week-long symptoms of dysphonia, dysphagia, and weakness of the right shoulder elevation, accompanied by a mild right temporal parietal headache with radiation to the ipsilateral ear. Physical examination showed signs compatible with a right XI, X, and XI cranial nerves involvement and also several vesicular lesions in the right ear's concha. He had a personal history of poliomyelitis and chickenpox. Laringoscopy demonstrated right vocal cord palsy. Brain MRI showed thickening and enhancement of right lower cranial nerves and an enhancing nodular lesion in the ipsilateral jugular foramen, in T1 weighted images with gadolinium. Cerebrospinal fluid (CSF) analysis disclosed a mild lymphocytic pleocytosis and absence of VZV-DNA by PCR analysis. Serum VZV IgM and IgG antibodies were positive. The patient had a noticeable clinical improvement after initiation of acyclovir and prednisolone therapy. The presentation of a VZV infection with isolated IX, X, and XI cranial nerves palsy is extremely rare. In our case, the diagnosis of Vernet syndrome as a result of VZV infection was made essentially from clinical findings and supported by analytical and imaging data.

Background: Accurate distinction of epithelioid hemangioma (EH) from its malignant mimics is paramount but remains challenging due to its wide morphological spectrum and lack of objective molecular markers. FOSB oncogenic activation was recently identified as a key event in endothelial proliferation. We sought to investigate the FOSB staining pattern in EH with angiolymphoid hyperplasia with eosinophilia (EH-AHLE) morphology and to evaluate its value in differential diagnosis of epithelioid vascular tumors. Methods: From the authors' files, 15 representative cases of EH-ALHE were selected and evaluated for their FOSB immunostaining pattern. Other vascular proliferations which can be morphological mimics were also tested: epithelioid hemangioendothelioma (EHE) (5 cases) and epithelioid angiosarcoma (EAS) (5 cases). Results: All 15 cases of EH-ALHE showed strong and homogeneous FOSB nuclear expression in endothelial cells with ample cytoplasm and intracytoplasmic vacuoles. All cases of EHE and EAS lacked FOSB immunoreactivity or showed only incidental weak FOSB immunoreactivity in less than 5 nuclei per lesion. Conclusions: FOSB immunohistochemistry is sensitive in the diagnosis of EH-ALHE, and allows differentiation from its histological mimics. An immunohistochemical panel including not only pan-cytokeratin AE1/AE3 and endothelial markers, but also FOSB, helps in the diagnosis of epithelioid vascular tumors.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compare the effectiveness of different individual interventions in recovery from work.