Repositório RCAAP

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Glioblastoma (GB) and brain metastases (BM) are the most common brain tumors in adults and are invariably associated with a dismal outcome. These highly malignant tumors share common features including increased invasion and migration of the primary or metastatic brain cancer cells, whose triggering mechanisms are largely unknown. Emerging evidence has suggested that the ubiquitin-conjugating enzyme E2C (UBE2C), essential for controlling cell cycle progression, is overexpressed in diverse malignancies, including brain cancer. This review highlights the crucial role of UBE2C in brain tumorigenesis and its association with higher proliferative phenotype and histopathological grade, with autophagy and apoptosis suppression, epithelial-to-mesenchymal transition (EMT), invasion, migration, and dissemination. High expression of UBE2C has been associated with patients' poor prognosis and drug resistance. UBE2C has also been proven as a promising therapeutic target, despite the lack of specific inhibitors. Thus, there is a need to further explore the role of UBE2C in malignant brain cancer and to develop effective targeted therapies for patients with this deadly disease.

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Purpose: To evaluate bleb morphology features of different glaucoma drainage devices (GDD) using magnetic resonance imaging (MRI). Materials and methods: Prospective cohort study of GDD and bleb morphology in consecutive glaucoma patients implanted with Ahmed Glaucoma Valve (AGV), Paul Glaucoma Implant (PGI), Baerveldt Glaucoma Implant (BGI) and Ahmed ClearPath (ACP) devices. Thirty-six eyes from 30 consecutive patients underwent standardized GDD implantation followed by MRI at least 1 month after surgery. Main outcomes included bleb volume and endplate position relative to the optic nerve. Secondary outcomes included intraocular pressure (IOP), medication and surgical complications during a 12-month follow-up. Results: Seven eyes were implanted with the AGV (19%), 5 with BGI (14%), 16 with PGI (44%) and 8 with ACP (22%). MRI scans were obtained 85 ± 66 days after surgery. Mean total bleb volume was 563 ± 390 mm3 . This bleb volume was inversely correlated with early post-operative IOP (day 7; rs = -0.3326, p = 0.0475) but positively correlated with IOP at 12 months (rs = 0.3592, p = 0.0341). No significant difference in total bleb volume was found between GDD types (p = 0.1223). A double-layered bleb was observed in 34 eyes (94%). The inferior bleb volume was significantly larger in PGI devices versus other GDD types (380 ± 205 vs. 193 ± 161 mm3 ; p = 0.0043). Distance from the endplate to the optic nerve was 9.5 ± 4.0 mm, similar across GDDs (p = 0.2519). Conclusions: Double-layered blebs are a common finding with GDDs. Bleb volume showed different correlations with IOP at distinct timepoints and the PGI device formed larger blebs. A standardized GDD implantation technique ensures a safe distance from the GDD endplate to the optic nerve.

Background and aims: Cardiovascular (CV) diseases show clear differences in clinical manifestation and treatment outcomes between men and women. To reduce sex disparities in achieving lipid-lowering therapy (LLT) goals, a sex-focused assessment is essential and more studies are needed to bring new evidence to clinicians. This study aims to assess the role of sex in attaining low-density lipoprotein cholesterol (LDL-C) goals, after correction for age, CV risk category, LLT intensity, and presence of mental health disorder and social deprivation. Methods: A retrospective cohort analysis of patients aged 40-85, followed in 1 hospital and 14 primary care centers in Portugal, using electronic health records from 1/1/2012 to 31/12/2020, was performed. The analysis considered an episode-based design, where exposure consists of any time when LLT was started or intensity changed. The likelihood of reaching the LDL-C goal according to contemporary ESC/EAS guidelines was modeled using multivariate Cox regression. LDL-C goal achievement at 180 days was defined as the outcome. The analysis was repeated at 30-day follow-up intervals up to 360 days, and also stratified by CV risk category. Results: We identified 40,032 exposure episodes (LLT initiation or intensity change) in 30,323 distinct patients. Male sex, older age, lower CV risk and increasing LLT intensity were associated with improved LDL-C control. Women were 22% less likely to reach the LDL-C goal than men (HR = 0.78, 95% CI:0.73, 0.82) independently of covariates. Conclusions: Women have a lower likelihood of attaining LDL-C goals than men after adjustment for LLT intensity, age, CV risk category, presence of mental health disorder and social deprivation. This finding underscores the need for further investigation and tailoring of LLT management strategies in women.

Os episódios de precipitação intensa ocorridos durante os meses de Inverno encontramse associados ao desencadear de movimentos de vertente, causando muitas vezes a obstrução das redes viárias, a destruição de edifícios e em certos casos até à perca de vidas. Através da avaliação da susceptibilidade e do recurso à análise geomorfológica da Área Metropolitana de Lisboa (AML) pretende-se identificar as áreas sensíveis à ocorrência de movimentos de vertente, contribuindo assim para uma melhor gestão do território, diminuindo desta forma o grau de exposição que o caracteriza. Recorrendo aos Sistemas de Informação Geográfica (SIG), constitui objectivo inicial deste trabalho, criar um inventário de movimentos de vertente baseado em foto-interpretação, construindo em seguida um modelo de avaliação da susceptibilidade da AML. O método estatístico utilizado foi o Valor Informativo (VI), método indirecto bivariado, que utiliza diversos factores de predisposição. Posteriormente foi feita a validação do modelo, o que permitiu aferir a sua qualidade e robustez e foi testada a sua capacidade preditiva. Constitui objectivo final deste trabalho criar um modelo de Risco da rede ferroviária da AML à ocorrência de movimentos de vertente, a partir do qual serão calculados os Custos Directos e Indirectos resultantes, para a totalidade da rede ferroviária, bem como para cada uma das linhas suburbanas da AML. A construção destes modelos tem por base o estipulado no “Guia Metodológico para a Produção de Cartografia Municipal de Risco e para a Criação de Informação Geográfica de Base Municipal” (2009).

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Although the prevalence of severe asthma is not high (5-10% of patients), it is responsible for a large part of the overall disease burden and costs (50-60% of total costs), especially if the condition remains uncontrolled (which occurs in around 40% of cases). Currently, for patients without disease control or presenting frequent exacerbations despite optimal therapy, add-on treatments, traditionally long-acting anticholinergics, oral corticosteroids (OCS) or biologic agents (monoclonal antibodies) are recommended.2 Nonetheless, the long-term use of oral/systemic corticosteroids (CS) is significantly associated with adverse effects, acute and chronic complications that may decrease health-related quality of life and worsen prognosis, thus requiring additional monitoring and management. Conversely, target therapies (i.e., omalizumab, mepolizumab, reslizumab, benralizumab and more recently, dupilumab) have been developed grounded on the different phenotypes and endotypes of severe asthma, and are gradually reducing the reliance on OCS (i.e., greater specificity for achieving disease control by reducing the risk of exacerbations and requirements for rescue medication and OCS, with limited adverse events).