Results from a population-based cohort study

Funding Information: We have read the journal's policy and the authors of this manuscript have the following competing interests: ARF reports travel grants from Roche and advisory board fees from Daiichi Sankyo, Gilead, Merck Sharp & Dohme, Novartis and Roche, outside the submitted work. DMB reports travel grants from LEO Farmacêuticos, Merck Sharp & Dohme, Ipsen, Janssen, Roche, and Novartis, advisory board fees from Janssen, Pfizer, Merck Sharp & Dohme, Angelini, AstraZeneca, and Novartis, and institutional grants from F. Hoffmann-La Roche, outside the submitted work. The other authors have declared that no competing interests exist. Funding Information: The authors acknowledge the RON network that cooperated in providing up-to-date information on cases diagnosed and treated with the drug of interest (participating institutions: Centro Hospitalar Universit?rio de S?o Jo?o, Centro Hospitalar Universit?rio Lisboa Norte, Centro Hospitalar Universit?rio do Algarve, Hospital de Braga, Centro Hospitalar e Universit?rio de Coimbra, Centro Hospitalar de Tr?s-os-Montes e Alto Douro, Hospital Central do Funchal, Centro Hospitalar de Vila Nova de Gaia/Espinho, Centro Hospitalar Lisboa Ocidental, Hospital Garcia de Orta, Centro Hospitalar Universit?rio Lisboa Central, Hospital Distrital de Santar?m, Centro Hospitalar de Entre o Douro e Vouga, Hospital da Senhora da Oliveira Guimar?es, Centro Hospitalar de Set?bal, Centro Hospitalar e Universit?rio do Porto, Centro Hospitalar Tondela Viseu, Hospital do Esp?rito Santo de ?vora, Centro Hospitalar Barreiro Montijo, Hospital Beatriz ?ngelo, Hospital do Santo Esp?rito da Ilha Terceira, Hospital do Divino Esp?rito Santo de Ponta Delgada, Hospital Pedro Hispano ? ULS Matosinhos, Hospital do Litoral Alentejano ? Santiago do Cac?m ? ULS Litoral Alentejano, Centro Hospitalar do Oeste, Centro Hospitalar M?dio Tejo, Hospital Jos? Joaquim Fernandes ? Beja ? ULS Baixo Alentejo, Centro Hospitalar Universit?rio da Cova da Beira, Centro Cl?nico Champalimaud, Hospitais CUF, Hospitais da Luz, Hospitais dos Lus?adas, Hospital Particular do Algarve). Publisher Copyright: © 2022 The AuthorsBackground: Real-world (RW) data may provide valuable information on the effectiveness and safety of medicines, which is particularly relevant for clinicians, patients and third-party payers. Evidence on the effectiveness of palbociclib plus fulvestrant is scarce, which highlights the need of additional studies. The aim of this study was to evaluate the effectiveness of palbociclib plus fulvestrant in advanced breast cancer (ABC). Materials and methods: We conducted a population-based retrospective cohort study and cases of interest were identified through the Portuguese National Cancer Registry database and additional data sources. Patients aged≥18 years, diagnosed with ABC and exposed to palbociclib plus fulvestrant between May 31, 2017 and March 31, 2019 were included. Patients were followed-up until death or cut-off date (February 28, 2021). Primary outcome was rw-progression-free survival (rwPFS). Secondary outcomes were rw-overall survival (rwOS), rw-time to palbociclib failure (rwTPF) and rw-time to next treatment (rwTTNT). Results: A total of 210 patients were included. Median age was 58 years (range 29–83) and 99.05% were female. Median follow-up time was 23.22 months and, at cut-off date, treatment had been discontinued in 189 patients, mainly due to disease progression (n = 152). Median rwPFS was 7.43 months (95% confidence interval [CI] 6.28–9.05) and 2-year rwPFS was 16.65% (95%CI 11.97–22.00). Median rwOS was 24.70 months (95%CI 21.58–29.27), median rwTPF was 7.5 months (95%CI 6.51–9.08) and median rwTTNT was 11.74 months (95%CI 10.33–14.08). Conclusion: Palbociclib plus fulvestrant seems an effective treatment for ABC in real-world context. Compared to registrations studies, rwPFS and rwOS were shorter in real-life setting.publishersversionpublishe

TempuSpacium Didática das Ciências Sociais - Estudos I

A educação para os media é, em geral, entendida enquanto etapa e meio para a educação para a cidadania. Nas suas diversas formas, os media, estão presentes, desde bem cedo, na vida das pessoas e, por isso, são determinantes na formação de cidadãos. No entanto, o efeito dos media é qualitativamente muito diferente em função dos grupos sociais e das desiguais capacidades dos recetores e utilizadores para aceder e fazer escolhas face ao enorme acervo de informação e de ofertas disponíveis através dos referidos media. Estas evidências acentuam a necessidade de a escola reforçar, criativa e permanentemente, o seu papel de facilitador na utilização das imensas possibilidades oferecidas pelos media, promovendo uma educação para escolhas valorativamente ponderadas face aos seus conteúdos. Não parece que tal esteja a acontecer de modo significativo

TempuSpacium Didática das Ciências Sociais - Estudos I

A educação para os media é, em geral, entendida enquanto etapa e meio para a educação para a cidadania. Nas suas diversas formas, os media, estão presentes, desde bem cedo, na vida das pessoas e, por isso, são determinantes na formação de cidadãos. No entanto, o efeito dos media é qualitativamente muito diferente em função dos grupos sociais e das desiguais capacidades dos recetores e utilizadores para aceder e fazer escolhas face ao enorme acervo de informação e de ofertas disponíveis através dos referidos media. Estas evidências acentuam a necessidade de a escola reforçar, criativa e permanentemente, o seu papel de facilitador na utilização das imensas possibilidades oferecidas pelos media, promovendo uma educação para escolhas valorativamente ponderadas face aos seus conteúdos. Não parece que tal esteja a acontecer de modo significativo

Arbustus unedo essence: morphological and genetic characterization of the strawberry tree of Castelo de Paiva

O medronheiro é um arbusto da região mediterrânica que pode ser encontrada por todo o país. Ao contrário do que verifica na região sul do país, no concelho de Castelo de Paiva é atribuída uma reduzida importância económica a esta espécie. Com o intuito de preservar e potenciar a produção desta espécie e contribuir para a dinamização da economia do concelho, procedeu-se à caracterização morfológica e genética de uma amostra da população de medronheiros de Castelo de Paiva. A caracterização morfológica e genética foi realizada para um total de 10 genótipos. Para tal recolheram-se 70 folhas aleatoriamente em cada árvore. Em 40 folhas mediu-se o comprimento, largura, comprimento do pedúnculo, peso fresco, peso seco e determinou-se a área foliar. Dos caracteres morfológicos analisados, aqueles que se revelaram mais úteis na distinção dos vários genótipos foram: comprimento do pedúnculo, peso fresco e peso seco. As restantes 30 folhas foram utilizadas para a caracterização genética. Esta caracterização foi realizada recorrendo a um marcador de DNA, ISSR. Os 5 primeiros exemplaresutilizados na técnica de ISSR demonstraram-se polimórficos. Os resultados da caracterização genética sugerem que a variabilidade genética na população é média a alta.The strawberry tree is a shrub native in the Mediterranean region and it can be found throughout Portugal. Unlike the case in the southern region of the country, in Castelo de Paiva a minor economic importance is given to this species. In order to preserve, to enhance the production of this species and to contribute to the boosting of the economy of the region, we proceeded to the characterization of a small sample population of this fruit tree of Castelo de Paiva in what concerns to its morphology and genetics. The morphological and genetic characterization was performed for a total of 10 genotypes. For this, 70 leaves were randomly collected from each tree. For 40 leaves, it was measured the length, the width, the peduncle length, the wet weight, the dry weight and determined the leaf area. Of the morphological characteristics analyzed, the ones that proved most useful in distinguishing the various genotypes were: the length peduncle, the wet weight and the dry weight. The remaining 30 leaves were used in the genetic characterization. This characterization was performed using a DNA marker, the ISSR. The 5 primers used in the ISSR technique proved to be polymorphic. The results from the genetic characterization suggest that variability in population genetics is medium to high

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Deliverable 4.3 (D4.3): Protocol for field collection and preservation of eDNA samples, EnvMetaGen project (Grant Agreement No 668981)

The overall goal of ERA Chair/EnvMetaGen project No 668981 is to expand the research and innovation potential of InBIO – Research network in Biodiversity and Evolutionary Biology, through the creation of an ERA Chair in Environmental Metagenomics. This field was selected as the focus of the ERA Chair, because Environmental DNA (eDNA) analysis is increasingly being used for biodiversity assessment, diet analysis, detection of rare or invasive species, population genetics and ecosystem functional analysis. In this context, the work plan of EnvMetaGen includes one work package dedicated to the Deployment of an eDNA Lab (WP4), which involves the training of InBIO researchers and technicians for implementing best practice protocols for the analysis of eDNA (Task 4.2). These protocols are essential for key application areas and to the development of research projects in association with business partners and other stakeholders, and thus to the strengthening of InBIO triple-helix initiatives (InBIO-Industry-Government; WP5). This report provides an overview of the current state of the art for collecting and preserving eDNA samples, with particular focus on vertebrate faecal samples, water samples and bulk invertebrate samples, which have been selected as key targets for the development of triple helix strategic initiatives (Task 5.3). The protocols already optimized and currently under development for the collection and preservation of eDNA samples are reported herein. Moreover, the future directions of sample collection and preservation at InBIO are discussed. This development was made possible through the recruitment of the ERA Chair team (WP2), secondments and Junior Researcher exchanges through the collaboration with international networks (WP3), an enhancement of computational infrastructure at InBIO (WP4) and participation of team members in workshops and conferences (WP6). Together, Deliverables D4.2-D4.5 (this document; Ferreira et al. 2018; Galhardo et al. 2018; Paupério et al. 2018) form a detailed account of the successful deployment of a fully functional eDNA lab under the EnvMetaGen project, and provide a valuable resource for eDNA practitioners in all spheres of the triple-helix model

Identification and microbial production of the raspberry phenol salidroside that is active against Huntington's disease

Sequence data from this article can be found in the GenBank/EMBL data libraries under accession numbers: KX262844.1 (RsUGT72B14, R. sachalinensis); AY547304.1 (RsUGT73B6. R. sachalinensis); NP_418458.1 (malE, E. coli); NP_415214.1 (pgm, E. coli); NP_415752.1 (galU, E. coli); NM_001180688.3 (aro10, S. cerevisiae), and NP_417484.1 (yqhD, E. coli).Edible berries are considered to be among nature's treasure chests as they contain a large number of (poly)phenols with potentially health-promoting properties. However, as berries contain complex (poly)phenol mixtures, it is challenging to associate any interesting pharmacological activity with a single compound. Thus, identification of pharmacologically interesting phenols requires systematic analyses of berry extracts. Here, raspberry (Rubus idaeus, var. Prestige) extracts were systematically analyzed to identify bioactive compounds against pathological processes of neurodegenerative diseases. Berry extracts were tested on different Saccharomyces cerevisiae strains expressing disease proteins associated with Alzheimer's, Parkinson's, or Huntington's disease or amyotrophic lateral sclerosis. After identifying bioactivity against Huntington's disease, the extract was fractionated and the obtained fractions were tested in the yeast model, which revealed that salidroside, a glycosylated phenol, displayed significant bioactivity. Subsequently, a metabolic route to salidroside was reconstructed in S. cerevisiae and Corynebacterium glutamicum. The best-performing S. cerevisiae strain was capable of producing 2.1 mM (640 mg L-1) salidroside from glucose in shake flasks, whereas an engineered C. glutamicum strain could efficiently convert the precursor tyrosol to salidroside, accumulating up to 32 mM (9,700 mg L-1) salidroside in bioreactor cultivations (yield: 0.81 mol mol-1). Targeted yeast assays verified that salidroside produced by both organisms has the same positive effects as salidroside of natural origin.We express our gratitude to Dr. Rute Neves (Chr. Hansen A/S, Denmark), Prof. Dr. Jochen Förster and Dr. Alexey Dudnik (The Nova Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Denmark), who coordinated the BacHBerry project. We also thank Prof. Dr. Ian Macreadie (Centre of Excellence for Alzheimer’s Disease Research & Care, School of Exercise, Biomedical & Health Sciences, Edith Cowan University, WA, Australia) for providing p416_GPD-GFP_AB42; Prof. Dr. Tiago Outeiro (University Medical Center Gottingen, Department of Neurodegeneration and Restorative Research, Germany) for providing W303-1A_Syn and W303-1A TU; Prof. Dr. Flaviano Giorgini (Department of Genetics and Genome Biology, University of Leicester, UK) for providing p425GAL1_HTT103Q; and Prof. Dr. Greg Petsko (Department of Biochemistry and Chemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, U.S.) for providing pYES_GAL1pr-FUS-GFP and pYES_CT.info:eu-repo/semantics/publishedVersio

Assessment of calcinosis in Portuguese patients with systemic sclerosis: a multicenter study

© The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR) 2023Introduction/objectives: The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis. Method: A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed. Results: We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02-6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28-9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2-14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7-34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001-0477, p = 0.015). Conclusions: Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors' variability. Key Points • Prevalence of subclinical calcinosis in SSc patients is substantial. • Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method. • Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis. • Anti-nuclear antibody positivity may be a protective factor for knee calcinosis.info:eu-repo/semantics/publishedVersio