Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Ambientalização curricular no contexto amazônico do Centro de Estudos Superiores de Tefé / Curricular environmentalization in the Amazon context of the Center for Higher Studies in Tefé

A educação ambiental através do currículo e mediante a transversalidade é a via seguida pelas universidades para consolidar conhecimentos, atitudes e valores ambientais na formação de profissionais. Isto é chamado de ambientalização curricular, que é uma direção de trabalho da educação superior à que, como tendência, se presta especial atenção nas principais universidades do mundo, mas não nas latino-americanas, as quais refletem demoras na implementação de estratégias deste tipo de trabalho educativo. O autor analisa as principais limitações que se manifestam e a necessidade do desenvolvimento de um currículo ambientalizado, adaptado ao contexto no que se formam os estudantes, que neste caso é o amazônico

Ambientalização curricular no contexto Amazônico do Centro de Estudos Superiores de Tefé / Curricular environmentalization in the Amazon context of the Center for Higher Studies in Tefé

A educação ambiental através do currículo e mediante a transversalidade é a via seguida pelas universidades para consolidar conhecimentos, atitudes e valores ambientais na formação de profissionais. Isto é chamado de ambientalização curricular, que é uma direção de trabalho da educação superior à que, como tendência, se presta especial atenção nas principais universidades do mundo, mas não nas latino-americanas, as quais refletem demoras na implementação de estratégias deste tipo de trabalho educativo. O autor analisa as principais limitações que se manifestam e a necessidade do desenvolvimento de um currículo ambientalizado, adaptado ao contexto no que se formam os estudantes, que neste caso é o amazônico

Multi-inflammatory Syndrome in Children Related to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Spain

Abstract Some clusters of children with a multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We describe the epidemiological and clinical features of children with MIS-C in Spain. MIS-C is a potentially severe condition that presents in children with recent SARS-CoV-2 infection.</jats:p

Current state-of-the-art and gaps in platform trials: 10 things you should know, insights from EU-PEARL

Summary: Platform trials bring the promise of making clinical research more efficient and more patient centric. While their use has become more widespread, including their prominent role during the COVID-19 pandemic response, broader adoption of platform trials has been limited by the lack of experience and tools to navigate the critical upfront planning required to launch such collaborative studies. The European Union-Patient-cEntric clinicAl tRial pLatform (EU-PEARL) initiative has produced new methodologies to expand the use of platform trials with an overarching infrastructure and services embedded into Integrated Research Platforms (IRPs), in collaboration with patient representatives and through consultation with U.S. Food and Drug Administration and European Medicines Agency stakeholders. In this narrative review, we discuss the outlook for platform trials in Europe, including challenges related to infrastructure, design, adaptations, data sharing and regulation. Documents derived from the EU-PEARL project, alongside a literature search including PubMed and relevant grey literature (e.g., guidance from regulatory agencies and health technology agencies) were used as sources for a multi-stage collaborative process through which the 10 more important points based on lessons drawn from the EU-PEARL project were developed and summarised as guidance for the setup of platform trials. We conclude that early involvement of critical stakeholder such as regulatory agencies or patients are critical steps in the implementation and later acceptance of platform trials. Addressing these gaps will be critical for attaining the full potential of platform trials for patients. Funding: Innovative Medicines Initiative 2 Joint Undertaking with support from the European Union’s Horizon 2020 research and innovation programme and EFPIA