SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Aplicação das tecnologias de modelagem 3D conjugada às técnicas tradicionais para o registro das gravuras rupestres do rio Madeira, Rondônia, Brasil

Nos últimos anos, os estudos de arte rupestre no Brasil têm tido um grande avanço quanto à construção de modelos interpretativos deste tipo de vestígio arqueológico ainda pouco conhecido e explorado. Apesar dos desafios em localizar, registrar e preservá-las ao longo do vasto território brasileiro, um número pequeno, mas devotado, de pesquisadores tem documentado e estudado minuciosamente milhares de pinturas e gravuras rupestres em várias regiões do país por meio de técnicas tradicionais. Apresentamos aqui um estudo de caso realizado no rio Madeira, no estado de Rondônia, no qual conjugamos a metodologia tradicional com novas tecnologias para o registro de gravuras rupestres, o laser scanning terrestre e a fotogrametria de luz estruturada. Essas novas tecnologias proporcionam, entre outras vantagens, precisão, acuidade e rapidez na documentação de gravuras rupestres, assim como de seu entorno paisagístico. Em última instância, o trabalho do arqueólogo é gerar modelos interpretativos do registro arqueológico, baseados em uma documentação o mais fiel possível para que esses modelos possam ser testados e revistos. As tecnologias de modelagem 3D elevam nossa capacidade a um novo patamar metodológico

Revisão sistematizada da literatura e opinião de peritos

Objective: The 3E (Evidence, Expertise, Exchange) Initiative is a multinational effort of rheumatologists aimed at developing evidence-based recommendations addressing specific questions relevant to clinical practice. The objective of the Portuguese contribution for the 3E Initiative was to develop evidence-based recommendations on how to investigate, follow-up and treat undifferentiated peripheral inflammatory arthritis (UPIA) adapted to local reality and develop additional recommendations considered relevant in the national context. Methods: An international scientific committee from 17 countries selected a set of questions concerning the diagnosis and monitoring of UPIA using a Delphi procedure. Evidence-based answers to each question were sought by a systematic literature search, performed in Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2009 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In a national meeting, a panel of 63 Portuguese rheumatologists used the evidence which was gathered to develop recommendations, and filled the gaps in the evidence with their expert opinion. Finally, national recommendations were formulated and agreement among the participants was assessed. Results: A total of 54754 references were identified, of which 267 were systematically reviewed. Thirteen national key recommendations about the investigation, follow-up and treatment of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to the established operational diagnosis of UPIA, eight recommendations were related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, serologies, autoantibodies, radiographs, magnetic resonance imaging and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity), one addressed monitoring of clinical disease activity in UPIA, one aimed to find an useful method/score to predict a definitive diagnosis and the last one was related to treatment. Conclusion: Portuguese evidence-based recommendations for the management of UPIA in everyday practice were developed. Their dissemination and implementation in daily clinical practice should help to improve practice uniformity and optimize the management of UPIA patients.publishersversionpublishe

Portuguese guidelines for the use of biological agents in rheumatoid arthritis - March 2010 update.

The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of rheumatoid arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of non-responders. Biological treatment should be considered in RA patients with a disease activity score 28 (DAS 28) superior to 3.2 despite treatment with 20mg/week of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 6 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, characterized by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of 0.6 in the DAS28 score. After 6 months of treatment response criteria is defined as a decrease of more than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).publishersversionpublishe

Practical guide for the use of biological therapies in rheumatoid arthritis - Update of December 2011

The authors review the practical aspects of biologi -cal therapy use for rheumatoid arthritis patients, commenting safety issues before and after treatment initiation and the best treatment strategies to optimize efficacy.publishersversionpublishe

Unraveling the genetic background of individuals with a clinical familial hypercholesterolemia phenotype

Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism caused by pathogenic/likely pathogenic variants in LDLR, APOB, and PCSK9 genes. Variants in FH-phenocopy genes (LDLRAP1, APOE, LIPA, ABCG5, and ABCG8), polygenic hypercholesterolemia, and hyperlipoprotein (a) [Lp(a)] can also mimic a clinical FH phenotype. We aim to present a new diagnostic tool to unravel the genetic background of clinical FH phenotype. Biochemical and genetic study was performed in 1,005 individuals with clinical diagnosis of FH, referred to the Portuguese FH Study. A next-generation sequencing panel, covering eight genes and eight SNPs to determine LDL-C polygenic risk score and LPA genetic score, was validated, and used in this study. FH was genetically confirmed in 417 index cases: 408 heterozygotes and 9 homozygotes. Cascade screening increased the identification to 1,000 FH individuals, including 11 homozygotes. FH-negative individuals (phenotype positive and genotype negative) have Lp(a) >50 mg/dl (30%), high polygenic risk score (16%), other monogenic lipid metabolism disorders (1%), and heterozygous pathogenic variants in FH-phenocopy genes (2%). Heterozygous variants of uncertain significance were identified in primary genes (12%) and phenocopy genes (7%). Overall, 42% of our cohort was genetically confirmed with FH. In the remaining individuals, other causes for high LDL-C were identified in 68%. Hyper-Lp(a) or polygenic hypercholesterolemia may be the cause of the clinical FH phenotype in almost half of FH-negative individuals. A small part has pathogenic variants in ABCG5/ABCG8 in heterozygosity that can cause hypercholesterolemia and should be further investigated. This extended next-generation sequencing panel identifies individuals with FH and FH-phenocopies, allowing to personalize each person’s treatment according to the affected pathway