52 research outputs found

    Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

    Get PDF
    Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6,809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA

    Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

    Get PDF
    Objective: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%

    Biodiversidade.

    Get PDF
    Neste capítulo, foi adotada uma definição ampla da biodiversidade, incorporando não apenas a complexidade do conceito, mas uma percepção de seu mecanismo, na geração de serviços ecossistêmicos. Essa visão holística da biodiversidade tem implicações importantes para políticas públicas, englobando a conservação de regiões biologicamente relevantes e seus processos ecológicos associados, além da pura proteção das espécies. O Brasil, reconhecido pela sua megabiodiversidade, possui a maior cobertura de florestas tropicais e a flora mais rica do mundo, além de abrigar uma fauna igualmente importante. Abriga diversos biomas terrestres e aquáticos onde se expressa frequentemente, de forma endêmica, o mais vasto e diversificado conjunto de espécies do planeta. Apesar dos avanços nas pesquisas para conhecimento da biodiversidade brasileira, ainda há muitas lacunas sobre a estrutura e composição dos ecossistemas e a maneira adequada de manejá-los, visando sua preservação. Um País megadiverso como o Brasil, com taxas tão altas de biodiversidade e endemismo, também tem grande responsabilidade de preservar sua rica biota e seus ecossistemas. De fato, o patrimônio natural do País inclui dois hotspots de biodiversidade (Mata Atlântica e Cerrado), seis Reservas da Biosfera, reconhecidas pela Organização das Nações Unidas para a Educação, a Ciência e a Cultura (Unesco), 12 ecorregiões prioritárias, definidas pelo Global 200 (WWF, 2001), 11 sítios Ramsar2, para a proteção de zonas úmidas, e quase 1.500 unidades de conservação. Este capítulo traz um panorama das forças motrizes, pressões, estados, impactos e respostas sobre a biodiversidade brasileira. SUMÁRIO: CAPÍTULO 4 – BIODIVERSIDADE; INTRODUÇÃO; ESPÉCIES E ECOSSISTEMAS: Alterações de comunidades e populações; Tráfico de animais silvestres; Espécies exóticas invasoras; Biodiversidade em números; Plantas, algas e fungos; Fauna aquática e terrestre; Avaliação do estado de conservação da biodiversidade brasileira; Espécies ameaçadas; Espécies da flora ameaçadas; Espécies da fauna ameaçadas; Plano de ação para a conservação e regulação do uso de espécies; Flora nativa; Fauna nativa; Espécies exóticas e invasoras; Perda de habitat, fragmentação e deterioração dos ecossistemas; Áreas e ações prioritárias para conservação, utilização sustentável e repartição dos benefícios da biodiversidade brasileira; RECURSOS GENÉTICOS: Biopirataria; Legislação nacional de proteção do patrimônio genético nacional e do conhecimento tradicional associado; Efeitos da política pública de proteção do patrimônio genético nacional, e do conhecimento tradicional associado, na conservação dos recursos genéticos; Proteção, gestão e uso sustentável dos recursos genéticos; Ratificação do Protocolo de Nagoia pelo Brasil; Conservação dos recursos genéticos vegetais e microbianos; GOVERNANÇA: Estratégia e Plano de Ação Nacionais para a Biodiversidade (Epanb); Avaliação das metas nacionais da biodiversidade; BIODIVERSIDADE E SAÚDE: Usos da biodiversidade: dos saberes tradicionais à biotecnologia; Biodiversidade e segurança alimentar; Emergência de zoonoses e biodiversidade; CONSIDERAÇÕES FINAIS; REFERÊNCIAS.ODS 2, ODS 3, ODS 9, ODS 12, ODS 14, ODS 15, ODS 17

    Interaction between resource identity and bacterial community composition regulates bacterial respiration in aquatic ecosystems

    No full text
    Abstract Resource identity and composition structure bacterial community, which in turn determines the magnitude of bacterial processes and ecological services. However, the complex interaction between resource identity and bacterial community composition (BCC) has been poorly understood so far. Using aquatic microcosms, we tested whether and how resource identity interacts with BCC in regulating bacterial respiration and bacterial functional diversity. Different aquatic macrophyte leachates were used as different carbon resources while BCC was manipulated through successional changes of bacterial populations in batch cultures. We observed that the same BCC treatment respired differently on each carbon resource; these resources also supported different amounts of bacterial functional diversity. There was no clear linear pattern of bacterial respiration in relation to time succession of bacterial communities in all leachates, i.e. differences on bacterial respiration between different BCC were rather idiosyncratic. Resource identity regulated the magnitude of respiration of each BCC, e.g. Ultricularia foliosa leachate sustained the greatest bacterial functional diversity and lowest rates of bacterial respiration in all BCC. We conclude that both resource identity and the BCC interact affecting the pattern and the magnitude of bacterial respiration in aquatic ecosystems

    Interaction between resource identity and bacterial community composition regulates bacterial respiration in aquatic ecosystems

    No full text
    Abstract Resource identity and composition structure bacterial community, which in turn determines the magnitude of bacterial processes and ecological services. However, the complex interaction between resource identity and bacterial community composition (BCC) has been poorly understood so far. Using aquatic microcosms, we tested whether and how resource identity interacts with BCC in regulating bacterial respiration and bacterial functional diversity. Different aquatic macrophyte leachates were used as different carbon resources while BCC was manipulated through successional changes of bacterial populations in batch cultures. We observed that the same BCC treatment respired differently on each carbon resource; these resources also supported different amounts of bacterial functional diversity. There was no clear linear pattern of bacterial respiration in relation to time succession of bacterial communities in all leachates, i.e. differences on bacterial respiration between different BCC were rather idiosyncratic. Resource identity regulated the magnitude of respiration of each BCC, e.g. Ultricularia foliosa leachate sustained the greatest bacterial functional diversity and lowest rates of bacterial respiration in all BCC. We conclude that both resource identity and the BCC interact affecting the pattern and the magnitude of bacterial respiration in aquatic ecosystems

    Postmenopausal Exercise Prevention Program (PEPP)

    No full text
    corecore