Regulation and function of elF2B in neurological and metabolic disorders.

Eukaryotic initiation factor 2B, eIF2B is a guanine nucleotide exchange, factor with a central role in coordinating the initiation of translation. During stress and disease, the activity of eIF2B is inhibited via the phosphorylation of its substrate eIF2 (p-eIF2α). A number of different kinases respond to various stresses leading to the phosphorylation of the alpha subunit of eIF2, and collectively this regulation is known as the integrated stress response, ISR. This targeting of eIF2B allows the cell to regulate protein synthesis and reprogramme gene expression to restore homeostasis. Advances within structural biology have furthered our understanding of how eIF2B interacts with eIF2 in both the productive GEF active form and the non-productive eIF2α phosphorylated form. Here, current knowledge of the role of eIF2B in the ISR is discussed within the context of normal and disease states focusing particularly on diseases such as vanishing white matter disease (VWMD) and permanent neonatal diabetes mellitus (PNDM), which are directly linked to mutations in eIF2B. The role of eIF2B in synaptic plasticity and memory formation is also discussed. In addition, the cellular localisation of eIF2B is reviewed and considered along with the role of additional in vivo eIF2B binding factors and protein modifications that may play a role in modulating eIF2B activity during health and disease.

Actions developed at the Instituto de Medicina Integral Prof. Fernando Figueira to confront the COVID-19 pandemic / Ações desenvolvidas no Instituto de Medicina Integral Prof. Fernando Figueira para enfrentamento à pandemia da COVID-19

Abstract The COVID-19 pandemic has brought countless challenges to the health institutions around the world, especially those located in countries such as Brazil, with large territorial dimensions and many social and economic differences. This technical report aims to publish the actions carried out and the products developed at the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) before and during the pandemic - from January 31st to September 4th, 2020 - facing it efficiently and effectively, seeking institutional sustainability. The mobilization of the professional staff at the institution was fundamental to create protocols ofas-sistance, adapt the physical structures in the hospital and outpatient care, care for the health professionals, offer teaching and research activities in the distance mode, articulate management members to make decisions based on systematically collected data on the pandemic situationat real time. All actions were carried out with a single objective of assisting all the patients affected by COVID-19 admitted at the institution.

Resumo A pandemia da COVID-19 trouxe incontáveis desafios para as instituições de saúde de todo o mundo, em especial as localizadas em países como o Brasil, com grande dimensão territorial e muitas diferenças sociais e econômicas. Este informe técnico tem como objetivo publicizar as ações realizadas e os produtos desenvolvidos no Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) antes e durante a pandemia - no período de 31 de janeiro até 04 de setembro de 2020 - enfrentando-a com eficiência e eficácia, buscando a sustentabilidade institucional. A mobilização do corpo profissional da instituição foi fundamental para a construir protocolos de atendimento, adaptar as estruturas físicas na assistência ao paciente em âmbito hospitalar e ambulatorial, cuidar dos profissionais de saúde, ofertar as atividades de ensino e pesquisa na modalidade à distância, articular os membros da gestão para tomar decisões baseadas em dados sistematicamente coletados sobre a situação da pandemia em tempo real. Todas as ações foram realizadas com um uníssono objetivo de atender a todos os pacientes acometidos pela COVID-19 admitidos na instituição.

Actions developed at the Instituto de Medicina Integral Prof. Fernando Figueira to confront microcephaly by Zika virus / Ações desenvolvidas no Instituto de Medicina Integral Prof. Fernando Figueira para enfrentamento à microcefalia pelo Zika vírus

Abstract Objectives: to publicize by inserting institutionally to the context of microcephaly care by Zika virus in the Northeast of Brazil and to describe the activities developed during the epidemic outbreak that occurred in the country in 2015. Methods: analysis on technical documents and institutional announcements in newspapers, on television and radio was carried out from August 2015 to July 2016. Results: the Central Nucleus to Monitor and Study Microcephaly at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP); took part in elaborating a Clinical and Epidemiological protocol for Professionals at Maternity Hospitals and Referral Services from the State Health Department of Pernambuco (SES/PE); IMIP became a National Referral Center in elaborating protocols to identify and monitor children with microcephaly, and a Benchmark Assistance for the State Health Department of Pernambuco. Technical meetings took place with the participation of clinical and medical professionals, researchers, professors and institutional managers, forums, training sessions and workshops along with national and international institutions, technical visits of international organizations and development of studies on Zika virus and microcephaly. Conclusions: the impact by notifying microcephaly cases caused mobilization of services at IMIP, reorganization of work processes and research developments.

Resumo Objetivos: publicizar a inserção institucional no contexto da atenção à microcefalia pelo vírus Zika na Região Nordeste do Brasil e descrever as atividades desenvolvidas durante o surto epidêmico ocorrido no país em 2015. Métodos: realizada análise de documentos técnicos e de divulgação institucionais e de registros da mídia impressa, televisiva e de rádio no período de agosto de 2015 a julho de 2016. Resultados: instituído o Núcleo Central de Monitoramento e Estudo da Microcefalia do Instituto de Medicina Integral Prof. Fernando Figueira (IMIP); participação na elaboração de Protocolo Clínico e Epidemiológico para Profissionais de Maternidades e Serviços de Referência pela Secretaria Estadual de Saúde de Pernambuco (SES/PE); IMIP tornou-se Centro de Referência Nacional na Elaboração de Protocolos para Identificação e Acompanhamento de Crianças com Microcefalia e Referência Assistencial para a SES/PE. Realizadas reuniões técnicas com a participação dos profissionais clínicos, pesquisadores, docentes e gestores da instituição, fóruns, treinamentos e oficinas de trabalho com instituições nacionais e internacionais, visita técnica de organismos internacionais e desenvolvimento de estudos sobre vírus Zika e microcefalia. Conclusões: o impacto causado pela notificação dos casos de microcefalia provocou mobilização dos serviços do IMIP, reorganização dos processos de trabalho e desenvolvimento de pesquisas.