Impairment of Adenosinergic System in Rett syndrome: Novel Therapeutic Target to Boost BDNF Signalling

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through A2AR it potentiates BDNF synaptic actions in healthy animals. We thus characterized several hallmarks of the adenosinergic and BDNF signalling in RTT and explored whether A2AR activation could boost BDNF actions. For this study, the RTT animal model, the Mecp2 knockout (Mecp2-/y) (B6.129P2 (C)-Mecp2tm1.1Bird/J) mouse was used. Whenever possible, parallel data was also obtained from post-mortem brain samples from one RTT patient. Ex vivo extracellular recordings of field excitatory post-synaptic potentials in CA1 hippocampal area were performed to evaluate synaptic transmission and long-term potentiation (LTP). RT-PCR was used to assess mRNA levels and Western Blot or radioligand binding assays were performed to evaluate protein levels. Changes in cortical and hippocampal adenosine content were assessed by liquid chromatography with diode array detection (LC/DAD). Hippocampal ex vivo experiments revealed that the facilitatory actions of BDNF upon LTP is absent in Mecp2-/y mice and that TrkB full-length (TrkB-FL) receptor levels are significantly decreased. Extracts of the hippocampus and cortex of Mecp2-/y mice revealed less adenosine amount as well as less A2AR protein levels when compared to WT littermates, which may partially explain the deficits in adenosinergic tonus in these animals. Remarkably, the lack of BDNF effect on hippocampal LTP in Mecp2-/y mice was overcome by selective activation of A2AR with CGS21680. Overall, in Mecp2-/y mice there is an impairment on adenosinergic system and BDNF signalling. These findings set the stage for adenosine-based pharmacological therapeutic strategies for RTT, highlighting A2AR as a therapeutic target in this devastating pathology.info:eu-repo/semantics/publishedVersio

An operational approach to high resolution agro-ecological zoning in West-Africa

Research ArticleThe objective of this work is to develop a simple methodology for high resolution crop suitability analysis under current and future climate, easily applicable and useful in Least Developed Countries. The approach addresses both regional planning in the context of climate change projections and pre-emptive short-term rural extension interventions based on same-year agricultural season forecasts, while implemented with off-the-shelf resources. The developed tools are applied operationally in a case-study developed in three regions of Guinea-Bissau and the obtained results, as well as the advantages and limitations of methods applied, are discussed. In this paper we show how a simple approach can easily generate information on climate vulnerability and how it can be operationally used in rural extension servicesinfo:eu-repo/semantics/publishedVersio

Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe.Peer Reviewe

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

Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe

Resultados Preliminares (ta Ventilação de Alta Frequência na Unidade de Neonatologia do Hospital São Francisco Xavier

No Hospital São Francisco Xavier foram ventilados durante o ano de 1996 (Janeiro 1996 a Dezembro 1996), sob o protocolo de ventilação de alta frequência (VAF) 17 recém-nascidos que cumpriram os critérios pré-estabelecidos para admissão no estudo.Estes critérios foram os seguintes: 1) critérios de idade ou peso: recém-nascidos com menos de 1500 gramas ou 31 semanas de idade gestacional com necessidade de ventilação mecânica exigindo Fi02 de 30% e frequência respiratória do ventilador maior que 10 ciclos minuto: 2) critérios clínicos: Silverman maior ou igual a 7: 3) critérios laboratoriais: PaCo2 maior de 60 mmHg e Pa02 menor de 50 mmHg ou saturação transcutânea, menor de 80% com FiO2 maior de 21% e, ou pH menor de 7.25: 4) critérios clínicos major: presença de síndroma de rotura de vias aéreas (air leak) ou enfisema intersticial. Excluiu-se a apneia de causa central com repercussão sistémica. Deu-se preferência ao nascimento no Hospital São Francisco Xavier.Utilizaram-se parâmetros de avaliação às 12, 48, 120 e 240 horas de vida de F102, PAM, Índice de oxigenação, défice de bases.Registou-se o peso, idade gestacional, sexo, tipo de parto e local, NTISS e CRIB à entrada, grau de gravidade de doença de membrana hialina (critério radiográfico) e ecografia transfontanelar. Avaliou-se o tempo de ventilação global, VAF, ventilação convencional, CPAP, mudanças de método de ventilação e critérios de displasia broncopulmonar.A VAF foi aplicada precocemente (<6 H de vida) a uma população de RN de muito baixo peso dos quais 41% tinham peso inferior a 1000 gramas. Os RN, em média estiveram sob vaf 5 +/- 4 dias a que se seguiram 16 +/- 14 dias de ventilação convencional, no global 24 +/- 21 dias de FiO2 maior de 21%.O índice de oxigenação é um critério de gravidade do quadro e da necessidade ventilatória. Os óbitos parecem ter sido influenciados pelo não uso de dexametasona e, ou surfactante. 100% dos sobreviventes estavam a respirar ar ambiente às 36 semanas de idade corrigida, ainda que aos 28 dias de vida 23% tivessem critérios de DBP. Dos 13 recém-nascidos sobreviventes 15% dos RN tiveram hemorragia intraventricular. Os valores encontrados pela escala de Brazy e teste de Griphits mostraram que o grau de lesão se situou no moderado risco da primeira e de um bom prognóstico a curto e médio prazo da segunda.Os resultados deste estudo são favoráveis a que se prossiga com VAF

Clinical and Laboratory Basis for the Diagnosis and Understanding of Neonatal Metabolic Diseases

The authors divide neonatal metabolic diseases into two major groups: intoxication and energy deficiency. The main signs which allow for the suspicion of the diagnosis are indicated for each group. The complementary examinations to be carried out by the Clinical Pathology Service of the Central Hospital and those which must be carried out by the metabolic diseases Reference Centre are reviewed. Based on the clinical framework and on the examination results, the authors establish five syndromatic groups to orientate diagnosis. The authors conclude by presenting differential diagnosis tables based on the original systematic classification by Jean-Marie Saudubray, with up-dated modifications from their own experience

Colestase Neonatal: Contribuição da Clínica e dos Exames Complementares para o Diagnóstico Diferencial (Dez Anos de Experiência)

Os autores apresentam o estudo retrospectivo de 25 casos de colestase neonatal, avaliando a contribuição dos exames complementares, particularmente da cintigrafia hepatobiliar, para o diagnóstico nos diversos grupos etiológicos e sua orientação clínica.Foram encontrados seis grupos etiológicos: Grupo I: Transitória multifactorial, secundária a prematuridade e/ou alimentação parentérica, sépsis e medicamentos (10 casos, 40%); Grupo II: Atrésia das vias biliares extra-hepáticas (4 casos, 16%); Grupo III: Hipoplasia das vias biliares intra-hepáticas (3 casos, 12%); Grupo IV: Hepatite neonatal (3 casos, 12%); Grupo V: Doenças metabólicas (3 casos, 12%); Grupo VI: Outras etiologias (2 casos, 8%). Verificou-se um claro predomínio da colestase transitória multifactorial, sendo esta, hoje em dia, a etiologia mais frequente nas unidades de cuidados intensivos neonatais. Neste grupo a média das idades gestacionais foi de 33 semanas, com um peso médio à nascença de 1802 gr, sendo 20% das crianças simultaneamente leves para a idade gestacional. Noventa por cento (90%) dos recém-nascidos deste grupo efectuou alimentação parentérica prolongada e 70% teve sépsis neonatal tardia. A grande maioria não teve nem acolia nem colúria. A evolução foi favorável, sem sequelas hepáticas. No grupo da atrésia das vias biliares, a totalidade dos recém-nascidos era de termo, sem complicações no período neonatal, todos adequados à idade gestacional. A grande maioria dos doentes teve acolia e colúria. A cintigrafia hepática demonstrou ausência de excreção de contraste para o intestino no grupo da atrésia das vias biliares extra-hepáticas (grupo II) e no da hipoplasia da vias biliares intra-hepáticas (grupo III). No grupo da colestase transitória multifactorial (grupo I), a totalidade dos casos evidenciou um atraso na excreção de contraste. Este exame revelou-se de extrema importância na selecção de doentes para a biópsia hepática, a qual confirmou o diagnóstico nos grupos II, III e V, não tendo sido realizada em nenhum doente das restantes etiologias (grupos I, IV e VI). Na abordagem da colestase neonatal é muito importante a história perinatal, a condição do recém-nascido (pré-termo, LIG, noxas), o exame físico e a observação cuidadosa da cor das fezes para orientação diagnóstica e selecção criteriosa dos exames complementares a efectuar. É fundamental o reconhecimento desta nova entidade, em que a colestase é o resultado da própria condição de prematuridade associada a factores iatrogénicos. A sua evolução é, habitualmente, favorável e o diagnóstico não deve passar pela realização de biópsia hepática