REALMS Study: Real-World Effectiveness and Safety of Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis in Portugal

Background: Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS). Objectives: To assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal. Methods: Retrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected. Results: Two-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were naïve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study. Conclusions: Therapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.info:eu-repo/semantics/publishedVersio

The modified patient enablement instrument: a Portuguese cross-cultural adaptation, validity and reliability study

"Article number: 16087"Enabling patients with asthma to obtain the knowledge, confidence and skills they need in order to assume a major role in the management of their disease is cost effective. It should be an integral part of any plan for long-term control of asthma. The modified Patient Enablement Instrument (mPEI) is an easily administered questionnaire that was adapted in the United Kingdom to measure patient enablement in asthma, but its applicability in Portugal is not known. Validity and reliability of questionnaires should be tested before use in settings different from those of the original version. The purpose of this study was to test the applicability of the mPEI to Portuguese asthma patients after translation and cross-cultural adaptation, and to verify the structural validity, internal consistency and reproducibility of the instrument. The mPEI was translated to Portuguese and back translated to English. Its content validity was assessed by a debriefing interview with 10 asthma patients. The translated instrument was then administered to a random sample of 142 patients with persistent asthma. Structural validity and internal consistency were assessed. For reproducibility analysis, 86 patients completed the instrument again 7 days later. Item-scale correlations and exploratory factor analysis were used to assess structural validity. Cronbach's alpha was used to test internal consistency, and the intra-class correlation coefficient was used for the analysis of reproducibility. All items of the Portuguese version of the mPEI were found to be equivalent to the original English version. There were strong item-scale correlations that confirmed construct validity, with a one component structure and good internal consistency (Cronbach's alpha >0.8) as well as high test-retest reliability (ICC=0.85). The mPEI showed sound psychometric properties for the evaluation of enablement in patients with asthma making it a reliable instrument for use in research and clinical practice in Portugal. Further studies are needed to confirm its responsiveness.Financial support for this work was provided by FEDER funds through the Operational Programme Competitiveness Factors-COMPETE and National Funds through FCT-Foundation for Science and Technology under the project POCI-01-0145-FEDER-007038, and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio

2,4,5-Triaminopyrimidines as blue fluorescent probes for cell viability monitoring: synthesis, photophysical properties, and microscopy applications

Monitoring cell viability is critical in cell biology, pathology, and drug discovery. Most cell viability assays are cell-destructive, time-consuming, expensive, and/or hazardous. Herein, we present a series of newly synthesized 2,4,5-triaminopyrimidine derivatives able to discriminate between live and dead cells. To our knowledge, these compounds are the first fluorescent nucleobase analogues (FNAs) with cell viability monitoring potential. These new fluorescent molecules are synthesized using highly efficient and cost- effective methods and feature unprecedented photophysical properties (longer absorption and emission wavelengths, environment-sensitive emission, and unprecedented brightness within FNAs). Using a live– dead Saccharomyces cerevisiae cell and theoretical assays, the fluorescent 2,4,5-triaminopyrimidine derivatives were found to specifically accumulate inside dead cells by interacting with dsDNA grooves, thus paving the way for the emergence of novel and safe fluorescent cell viability markers emitting in the blue region. As the majority of commercially available viability dyes emit in the green to red region of the visible spectrum, these novel markers might be useful to meet the needs of blue markers for co-staining combinations

Short-chain di-ureasil ormolytes doped with potassium triflate: Phase diagram and conductivity behavior

Di-urea cross-linked poly(oxyethylene)/siloxane hybrids, synthesized by the sol-gel process and containing a wide concentration range of potassium triflate, KCF3SO3, have been analyzed by x-ray diffraction and differential scanning calorimetry. The pseudo-phase diagram proposed has been taken into account in the interpretation of the complex impedance measurements. The xerogels prepared are obtained as transparent, thin monoliths . At room temperature the highest conductivity found was 2 x 10-6Scm-1.Fundação para a Ciência e a Tecnologia (FCT

Impairment of Adenosinergic System in Rett syndrome: Novel Therapeutic Target to Boost BDNF Signalling

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through A2AR it potentiates BDNF synaptic actions in healthy animals. We thus characterized several hallmarks of the adenosinergic and BDNF signalling in RTT and explored whether A2AR activation could boost BDNF actions. For this study, the RTT animal model, the Mecp2 knockout (Mecp2-/y) (B6.129P2 (C)-Mecp2tm1.1Bird/J) mouse was used. Whenever possible, parallel data was also obtained from post-mortem brain samples from one RTT patient. Ex vivo extracellular recordings of field excitatory post-synaptic potentials in CA1 hippocampal area were performed to evaluate synaptic transmission and long-term potentiation (LTP). RT-PCR was used to assess mRNA levels and Western Blot or radioligand binding assays were performed to evaluate protein levels. Changes in cortical and hippocampal adenosine content were assessed by liquid chromatography with diode array detection (LC/DAD). Hippocampal ex vivo experiments revealed that the facilitatory actions of BDNF upon LTP is absent in Mecp2-/y mice and that TrkB full-length (TrkB-FL) receptor levels are significantly decreased. Extracts of the hippocampus and cortex of Mecp2-/y mice revealed less adenosine amount as well as less A2AR protein levels when compared to WT littermates, which may partially explain the deficits in adenosinergic tonus in these animals. Remarkably, the lack of BDNF effect on hippocampal LTP in Mecp2-/y mice was overcome by selective activation of A2AR with CGS21680. Overall, in Mecp2-/y mice there is an impairment on adenosinergic system and BDNF signalling. These findings set the stage for adenosine-based pharmacological therapeutic strategies for RTT, highlighting A2AR as a therapeutic target in this devastating pathology.info:eu-repo/semantics/publishedVersio

Subsídios técnicos para a indicação geográfica de procedência do Vale do Submédio São Francisco: uva de mesa e manga.

bitstream/CPATSA-2010/42261/1/SDC222.pd

Progress in Identifying High Nature Value Montados: Impacts of Grazing on Hardwood Rangeland Biodiversity

Due to their complex structure and traditional low-intensity management, Portuguese oak woodland rangelands known as montados are often considered high nature value (HNV) farming systems, and as such, they may be deemed eligible for subsidies and incentives by governmental and nongovernmental agencies. Too little is known about how the HNV concept might be applied to conserve complex silvopastoral systems. These systems, due to their structural and functional complexity at multiple scales, tend to support high levels of biodiversity. Montados are in sharp decline as a result of the rapid specialization of land management that, through simplification, undermines multifunctionality. Understanding how changes in management influence these systems and their biodiversity is needed for prioritizing conservation efforts and for ensuring they remain HNV systems. On the basis of a field survey in 58 plots distributed among 29 paddocks on 17 farms, we conducted an integrated analysis of the relationship between grazing intensity and biodiversity in montados of similar biophysical and structural characteristics. Data on management were obtained through interviews, and biodiversity data (vegetation, macrofungi, birds, herpetofauna) were obtained through specific field protocols. Additional spatial data, such as soil characteristics, slope, land cover, and linear landscape elements, were also analyzed. The results show no overall biodiversity variation as a result of different management practices. However, different groups of species react differently to specific management practices, and within a pasture, grazing impacts are heterogenous. In low grazing intensity plots, macrofungi species richness was found to be higher, while bird species richness was lower. Using tree regeneration as proxy for montado sustainability, results show less tree regeneration in areas with higher forage quality and more intense grazing. Pathways for future progress are proposed, including creating areas within a paddock that attract grazing away from where regeneration is desired

Progress in analytical approaches integrating Livestock and Biodiversity to identify HNV Montados

The World Congress Silvo-Pastoral Systems 2016 aims to gather researchers from different disciplines, practitioners and policy makers at different governance levels that deal with the management and sustainability of silvo-pastoral systems. In this way the congress will create a fertile context to progress through interdisciplinarity research approaches that can help translate scientific knowledge into new adaptive management solutions, and thus bridge from science to practice. The aim is also to gather and compare knowledge from silvo-pastoral systems around the world, which share drought as a limiting factor, so that they can be discussed and evaluated