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- Methamphetamine promotes a-tubulin deacetylation in endothelial cells: The protective role of acetyl-L-carnitinePublication . Fernandes, Sílvia; Salta, Sofia; Summavielle, TeresaMethamphetamine (METH) is a powerful psychostimulant drug used worldwide for its reinforcing properties. In addition to the classic long-lasting monoaminergic-disrupting effects extensively described in the literature, METH has been consistently reported to increase blood brain barrier (BBB) permeability, both in vivo and in vitro, as a result of tight junction and cytoskeleton disarrangement. Microtubules play a critical role in cell stability, which relies on post-translational modifications such as a-tubulin acetylation. As there is evidence that psychostimulants drugs modulate the expression of histone deacetylases (HDACs), we hypothesized that in endothelial cells METH-mediation of cytoplasmatic HDAC6 activity could affect tubulin acetylation and further contribute to BBB dysfunction. To validate our hypothesis, we exposed the bEnd.3 endothelial cells to increasing doses of METH and verified that itleads to an extensivea-tubulin deacetylation mediated by HDACs activation. Furthermore, since we recently reported that acetyl-L-carnitine (ALC), a natural occurring compound, prevents BBB structural loss in a context of METH exposure, we reasoned that ALC could also preserve the acetylation of microtubules under METH action. The present results confirm that ALC is able to prevent METH-induced deacetylation providing effective protection on microtubule acetylation. Although further investigation is still needed, HDACs regulation may become a new therapeutic target for ALC.
- Betulinic acid for glioblastoma treatment: Reality, challenges and perspectivesPublication . Fernandes, Sílvia; Vieira, Mariana; Prudêncio, Cristina; Ferraz, RicardoBetulinic acid is a naturally occurring compound that can be obtained through methanolic or ethanolic extraction from plant sources, as well as through chemical synthesis or microbial biotransformation. Betulinic acid has been investigated for its potential therapeutic properties, and exhibits anti-inflammatory, antiviral, antimalarial, and antioxidant activities. Notably, its ability to cross the blood–brain barrier addresses a significant challenge in treating neurological pathologies. This review aims to compile information about the impact of betulinic acid as an antitumor agent, particularly in the context of glioblastoma. Importantly, betulinic acid demonstrates selective antitumor activity against glioblastoma cells by inhibiting proliferation and inducing apoptosis, consistent with observations in other cancer types. Compelling evidence published highlights the acid’s therapeutic action in suppressing the Akt/NFκB-p65 signaling cascade and enhancing the cytotoxic effects of the chemotherapeutic agent temozolomide. Interesting findings with betulinic acid also suggest a focus on researching the reduction of glioblastoma’s invasiveness and aggressiveness profile. This involves modulation of extracellular matrix components, remodeling of the cytoskeleton, and secretion of proteolytic proteins. Drawing from a comprehensive review, we conclude that betulinic acid formulations as nanoparticles and/or ionic liquids are promising drug delivery approaches with the potential for translation into clinical applications for the treatment and management of glioblastoma.
- Family caregiver support strategies and tools to promote caregiver mental and emotional supportPublication . Silva, Regina; Fernandes, Sílvia; Portugal, PaulaIntroduction: Caring for family members with severe mental illness poses a great risk to the health of caregivers, being associated with the development of emotional, mental and physical health problems. The Family Caregiver Support Project aims to empower informal caregivers, through access to relevant medical information, which promotes self-confidence and skills, both in the care of family members and in relation to their own needs. Methods: Partners from eight European countries participated in this project, including ESS|P.PORTO, in the period between 01/11/2018 and 31/10/2020. Results: This project resulted in the creation of a Guide and Resource Pack for training informal caregivers, accessible through a free online platform that can be accessed through a mobile application. All materials were produced in multiple languages and widely disseminated. Conclusion: The products and contents are still available, with an estimated strong impact on the training of informal caregivers, improving their quality of life.
- CytoPath®Easy: screening of cervical cancerPublication . Fernandes, Sílvia; Vilarinho, Ana Sofia; Silva, ReginaRecently, CytoPath®Easy kit was created by DiaPath S.p.A. and started to be commercially available for the screening of cervical cancer. Using this methodology, epithelial cells are immersed in a preservative liquid, and a thin-layer of cells in the slide is obtained through gravity sedimentation and filtration. The main objectives of this study are to evaluate the efficacy for the processing of cervical samples, for the detection of pre-neoplastic lesions and for the nucleic preservation and extraction by the kit. For this purpose, 215 cervical samples obtained by self-sampling were used: 174 were collected and processed by CytoPath® Easy and, as a control, 41 were collected and processed by the Thinprep® method. The samples were processed, stained by the Papanicolaou method, and independently evaluated microscopically for various morphological parameters; nucleic acids were isolated and evaluated for purity and integrity by spectrophotometry. Results obtained showed that both methods have a good performance, allowing the morphological evaluation of the cervical epithelium. However, the statistical analysis reveals that the methods are different from each other, with overall lower results being obtained in the method under study (p<0.001). In turn, both methods allow the extraction of good quality and quantity of DNA. Although some differences were found regarding morphology of the cells fixed and processed by the CytoPath®Easy method, this new methodology reveals efficient for the preservation of nucleic acids. Thus, its use in cervical cancer screening is recommended.
- Rastreio organizado do cancro do colo do útero açores – Perspetiva de um novo paradigmaPublication . Maciel, Débora; Fernandes, Sílvia; Silva, Regina A.O cancro do colo do útero é um dos cancros mais frequentes na mulher a nível global. Em 2010, foi implementado o programa de Rastreio Organizado do Cancro do Colo do Útero dos Açores (ROCCA) usando como teste primário o método de citologia líquida para a identificação precoce de lesões precursoras. Em 2020 foi implementada uma nova metodologia de rastreio, o teste de HPV mRNA - AptimaTM HPV Assay (Hologic), seguido de genotipagem. Este trabalho tem como objetivo avaliar a eficácia da implementação do ROCCA, bem como a adequabilidade do método molecular enquanto ferramenta de rastreio.
- Desenvolvimento de uma laminoteca digitalPublication . Silva, Regina; Duarte, Raquel; Fernandes, SílviaDigital Cytology consists in the conversion of a glass slide into a digital image. The application of digital cytology in education, conferences, telecytology, publications and cytology websites has shown increased accessibility to cytology, along with the quality and efficiency improvement of the health services. In this study we intend to develop an Online Slide Library of gynecological cytology available to students for the gynecological cytology One hundred samples of gynecological cytology were selected and scanned by the whole slide imaging method. The Online Slide Library was created with HyperText Markup Language 5 and the digital images sharing within the Library was conducted using the institution network server. In education, the Online Slide Library developed allows the easier access to the study of gynecologic cytology as well as the access to rare and/or old samples. Also several students can observe the same case simultaneously with this method of digital cytology. The results of the present work allow to conclude that the Online Slide Library is a complementary tool for the gynecological cytology study.
- Family caregiver support—a facilitator to empower family caregiversPublication . Fernandes, Sílvia; Portugal, Paula; Mullins, Lhara; Power, Martin; Letica-Crepulja, Marina; Stevanović, Aleksandra; Frančišković, Tanja; Silva, ReginaMental disorders are highly prevalent, placing an enormous burden on individuals, society and economy. Research shows that family members who provide care to individuals with chronic or disabling mental conditions are themselves at risk. As a response to this problem, the project ‘Family Caregiver Support - Strategies and tools to promote the mental and emotional health of caregivers’ emerged, funded by Erasmus + Program and carried out by 8 European partners including ESS|P.PORTO.
- Validation of CINtec® PLUS cytology kit in the diagnosis of persistent HPV infections - Cohort study in the Portuguese populationPublication . Abreu, Ângela; Silva, Regina; Fernandes, SílviaThe use of the CINtec® PLUS Cytology Kit as a complementary method of diagnosis is intended to contribute to a risk assessment of CIN II+ cervical lesions development, thus avoiding unnecessary colposcopy in negative cases. This method has proved to be effective in the follow-up of cervical lesions, although there is need for consistency in the approach of equivocal or negative cytological results, with persistent positive High-Risk Human Papillomavirus (HR-HPV) test. Aims: The present study intends to retrospectively evaluate the capacity of the CINtec® to add information to the clinical practice within the screening and follow-up of cervical lesions. Additionally, this study intends to define criteria for CINtec® referral in order to maximize its utilization in the Portuguese context. Materials and Methods: For this purpose, 225 cases with CINtec® PLUS Cytology Kit and histology results were used, and data were analysed and compared according to the cytology and HR-HPV molecular test results. Results: The data of this study show that CINtec® PLUS Cytology Kit is a valid test for the diagnosis of persistent HPV lesions (p = 0.0005), with excellent sensitivity and reliable values of specificity. Relevant patient groups to apply the kit are in agreement with the manufacturer recommendations: women with ASC-US/LSIL result and NILM cytology with HPV-positive test, essentially over 30 years old. Conclusions: Although clinical data and previous cytological information must help guiding, authors considered that CINtec® is a really valid test for the prognosis of persistent HPV infections in the female population.
- CytoPath®Easy processing method validation through cervical self-samplingPublication . Fernandes, Sílvia; Martins, C.; Silva, ReginaLiquid-based cytology is mostly used for the identification of pre-neoplastic and neoplastic cells of cérvix uteri, and many manual and automatic methodologies are available on the market. This study aims to validate a new manual liquid-based processing method - the CytoPath® Easy Kit, for its routine use in some cytology laboratories.
- Projeto SMART PATIENTS - holistic empowerment of citizens to become experts in their own healthPublication . Fernandes, Sílvia; Jesus, Ângelo; Patrício, Brígida; Melo, Cristina; Tavares, Diana; Silva, ReginaAlinhado com o Quadro Estratégico da UE para a Saúde, o projeto Smart Patients tem como principal objetivo capacitar os cidadãos, colocando-os no centro do sistema e envolvendo-os na gestão da sua própria saúde. Assim, o projeto visa aumentar o grau de literacia em saúde dos cidadãos, desenvolvendo as suas competências e autoconfiança na gestão das suas necessidades de saúde. O projeto foi coordenado localmente pela ESS | P. PORTO, com a participação de 5 Áreas Técnico-Científicas, em colaboração com o consórcio de sete países europeus, e decorreu no período entre 01/09/2016 e 31/10/2018. Como resultado deste projeto, foram criados materiais de sensibilização, orientação e informação para os cidadãos; uma plataforma online para partilha de materiais e ferramentas; uma página web e folhetos informativos; e um aplicativo móvel. Todos os materiais foram traduzidos em vários idiomas e amplamente divulgados. É expectável que os produtos e conteúdos desenvolvidos tenham um forte impacto na capacitação da saúde dos cidadãos europeus.