Mutational spectrum of cystinosis in Portugal, 1998-2017

Artigo original publicado em inglês: Ferreira F, Leal I, Sousa D, et al. CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population. Open J Genet. 2018 Dec 18;8(4):91-100. doi:10.4236/ojgen.2018.84008A cistinose é uma doença metabólica multisistémica, autossómica recessiva caracterizada por uma acumulação de cistina em diferentes órgãos e tecidos devido a uma deficiência no transporte de cistina para o exterior dos lisossomas. O gene responsável pela doença, CTNS, está localizado no cromossoma 17 e codifica para uma proteína de membrana lisossomal, a cistinosina. Neste trabalho foram estudados doentes não relacionados provenientes das consultas de adultos e pediatria de diferentes hospitais de Portugal continental e ilhas, que apresentavam proteinuria não-nefrótica, hipercalciúria, hipocaliemia, hiperaminoacidúria, glicosúria e hipofosfatemia, sugestivo de síndroma de Fanconi e queixas oculares. Bioquimicamente, a cistina intraleucocitária foi quantificada, tendo-se igualmente efetuado a caracterização molecular do gene CTNS, inicialmente apenas direcionado para a pesquisa da deleção de 57-kb, seguida da sequenciação de todos os exões codificantes do gene CTNS. Desde 1998 a 2017, 21 doentes cistinóticos foram bioquimicamente caracterizados. Entretanto, 4 destes doentes faleceram e dos restantes 17, apenas 11 foram estudados para o gene CTNS. Verificouse que 5 destes 11 doentes foram homozigóticos para a deleção de 57-kb (10/22; 45,5%), e outros 5 foram compostos heterozigóticos para esta mutação (15/22; 68,2%). As outras mutações identificadas foram: p.Q128X (c.721 C>T; 2/22), p.S139F (c.755 C>T; 4/22) e c.18-21delGACT (p.T7FfsX7; 1/22). Todos estes 17 doentes cistinóticos estão em tratamento, sendo que 84% são adultos, 16% são crianças jovens e 54,5% são transplantados renais. Este estudo efetuado ao longo de vários anos, reflete a experiência no diagnóstico e monitorização dos doentes cistinóticos. Além disso, a caracterização das mutações encontradas no gene CTNS, ressalta a importância para um screening inicial da deleção de 57-kb e permite um futuro aconselhamento genético aos casais de risco.Cystinosis is a multisystemic autosomal recessive deficiency of the lysossomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems were studied. Intraleukocyte cystine levels were determined and molecular analysis performed, to determine the presence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. From 1998 to 2017, 21 cystinotic patients were biochemically diagnosed. From the remaining 17 (4 deceased), 11 were studied for CTNS gene. Five out of 11 patients were homozygous for the 57-kb deletion (10/22; 45.5%), and other 5 were compound heterozygous for this variant (15/22; 68.2%). The other mutations found were p.Q128X (c.721 C>T; 2/22), p.S139F (c.755 C>T; 4/22) and c.18-21delGACT (p.T7FfsX7; 1/22). All of these 17 cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in Portugal and it could be the basis for future genetic counseling in cistinotic patients.info:eu-repo/semantics/publishedVersio

CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population

Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective : This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene . Methods : Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS , followed by direct sequencing of the coding exons of CTNS . Results : From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22; 45.5%), and other five were compound heterozygous for this variant (15/22; 68.2%). The other mutations found were p.Q128X (c.721 C>T; 2/22), p.S139F (c.755 C>T; 4/22) and c.18-21delGACT (p.T7FfsX7; 1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.info:eu-repo/semantics/publishedVersio

Parasitas Pulmonares em Pequenos Ruminantes: Mais Conhecimento, Melhor Diagnóstico

A pneumonia parasitária por nematodes da superfamília Trichostrongyloidea e Metastrongyloidea, também conhecida como estrongilose pulmonar, apresenta elevada prevalência nalgumas regiões geográficas, mas tem merecido pouca atenção por parte dos Médicos Veterinários e investigadores [1,2]. Os estudos de prevalência disponíveis assentam predominantemente na deteção de lesões pulmonares em matadouro e no diagnóstico in vivo, com recurso à técnica de Baermann. No entanto, a velocidade de processamento das carcaças no matadouro limita substancialmente a probabilidade de deteção de lesões características de estrongilose e a técnica de Baermann, apesar de ser considerada a gold standard para diagnóstico in vivo, apresenta uma sensibilidade que não ultrapassa os 90%, é demorada e exige conhecimentos técnicos para a sua correta execução [3,4,5]. Em Portugal, do ponto de vista clínico, estas parasitoses são subdiagnosticadas, na medida em que a pesquisa de parasitas pulmonares raramente é incluída nos testes parasitológicos de rotina, requisitados pelos Médicos Veterinários aos laboratórios [6], o que, associado à escassez de investigação científica na área, cria uma lacuna no conhecimento da distribuição geográfica e de outros aspetos da epidemiologia destas infeções, comprometendo o seu tratamento e controlo. Apesar da desparasitação regular (anual ou bianual) de pequenos ruminantes estar amplamente instituída, alguns princípios ativos frequentemente utilizados para o controlo de parasitas gastrointestinais são pouco eficazes nos nematodes pulmonares, particularmente nalgumas espécies da família Protostrongylidae, pelo que a abordagem terapêutica deve ser integrada e assente no diagnóstico parasitológico prévio. Assim, este trabalho, assente na revisão da bibliografia disponível e na experiência prática dos técnicos e investigadores do Laboratório de Anatomia Patológica da Escola Superior Agrária de Viseu (LAP, ESAV) e do Laboratório de Parasitologia Victor Caeiro da Universidade de Évora (LPVC, UE), pretende sensibilizar os profissionais de saúde animal e investigadores dedicados aos pequenos ruminantes para as infeções por nematodes pulmonares, fornecendo ainda ferramentas de diagnóstico laboratorial acessíveis e orientações para a abordagem terapêutica e profilática.info:eu-repo/semantics/publishedVersio

Identification of clusters of asthma control: A preliminary analysis of the inspirers studies

This work was funded by ERDF (European Regional Development Fund) through the operations: POCI- -01-0145-FEDER-029130 (“mINSPIRERS—mHealth to measure and improve adherence to medication in chronic obstructive respiratory diseases - generalisation and evaluation of gamification, peer support and advanced image processing technologies”) co-funded by the COMPETE2020 (Programa Operacional Competitividade e Internacionalização), Portugal 2020 and by Portuguese Funds through FCT (Fundação para a Ciência e a Tecnologia).© 2020, Sociedade Portuguesa de Alergologia e Imunologia Clinica. All rights reserved. Aims: To identify distinct asthma control clusters based on Control of Allergic Rhinitis and Asthma Test (CARAT) and to compare patients’ characteristics among these clusters. Methods: Adults and adolescents (≥13 years) with persistent asthma were recruited at 29 Portuguese hospital outpatient clinics, in the context of two observational studies of the INSPIRERS project. Demographic and clinical characteristics, adherence to inhaled medication, beliefs about inhaled medication, anxiety and depression, quality of life, and asthma control (CARAT, >24 good control) were collected. Hierarchical cluster analysis was performed using CARAT total score (CARAT-T). Results: 410 patients (68% adults), with a median (percentile 25–percentile 75) age of 28 (16-46) years, were analysed. Three clusters were identified [mean CARAT-T (min-max)]: cluster 1 [27(24-30)], cluster 2 [19(14-23)] and cluster 3 [10(2-13)]. Patients in cluster 1 (34%) were characterised by better asthma control, better quality of life, higher inhaler adherence and use of a single inhaler. Patients in clusters 2 (50%) and 3 (16%) had uncontrolled asthma, lower inhaler adherence, more symptoms of anxiety and depression and more than half had at least one exacerbation in the previous year. Further-more, patients in cluster 3 were predominantly female, had more unscheduled medical visits and more anxiety symp-toms, perceived a higher necessity of their prescribed inhalers but also higher levels of concern about taking these inhalers. There were no differences in age, body mass index, lung function, smoking status, hospital admissions or specialist physician follow-up time among the three clusters. Conclusion: An unsupervised method based on CARAT--T, identified 3 clusters of patients with distinct, clinically meaningful characteristics. The cluster with better asthma control had a cut-off similar to the established in the validation study of CARAT and an additional cut-off seems to distinguish more severe disease. Further research is necessary to validate the asthma control clusters identified.publishersversionpublishe

práticas artísticas no ensino básico e secundário

Educação Artística: integrar a inovação. A educação artística apresenta-se como um território a re-cartografar, numa atualização tão rápida quanto aquela que ocorre no campo artístico. As propostas publicadas neste número 11 da Revista Matéria-Prima trazem essa diversidade de abordagens, com novidades conceptuais que estabelecem as devidas relações entre educação e cidadania, participação, sustentabilidade, cultura visual, e também com alguma atenção sobre os debates pós-coloniais e as questões de género. Os 16 artigos reunidos neste 11º número da Revista Matéria-Prima trazem a realidade operativa quer na formação de professores e quer na formulação dos discursos pedagógicos, suas justificações e suas propostas alternativas.As propostas apresentadas devolvem o debate ao terreno, e alargam-no. Provocam as periferias, convocam abordagens diferenciadas sobre o tema da arte e da educação. Em todas elas a proposta de crescimento através da arte, que hoje implica cada vez mais cidadania, crítica, criatividade, interligação, comprometimento, participação.info:eu-repo/semantics/publishedVersio

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

estudos artísticos

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Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI