IMPLEMENTACIÓN DE JUEGOS DE REHABILITACIÓN EN UN NIÑO CON SÍNDROME FOXP1

O presente estudo teve como objetivo desenvolver e validar uma estratégia de jogo adaptado à reabilitação da função psicomotora numa criança portadora de FOXP1, indo de encontro às necessidades identificadas pelos cuidadores. Participou neste estudo uma criança de 4 anos com síndrome de FOXP1. Realizou-se uma entrevista semiestruturada com a cuidadora, que foi transcrita e codificada com base na Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF). Foi ainda implementada a Medida Canadense de Desempenho Ocupacional. Posteriormente, prosseguiu-se a testes de implementação adaptada dos jogos analógicos Crazy Cups e Go Go Gelato! e de componentes de um jogo digital. Durante estas sessões realizou-se registo em vídeo para permitir a análise qualitativa e quantitativa do comportamento psicomotor. Os resultados demonstraram que as componentes como os autocuidados, independência fora de casa, mobilidade, socialização e recreação tranquila foram destacados como importantes para a cuidadora, estando modificados por dificuldades marcadas na organização motora e na integração de estímulos. Na implementação dos jogos ocorreram diferenças no número interações entre o jogo analógico e o jogo digital, com destaque para um maior número de interações no jogo digital. Foi ainda percetível uma evolução no número das interações positivas da primeira para a segunda sessão. Este estudo contribuiu para a adaptação de jogos na população pediátrica. A perspetiva do cuidador constitui-se uma ferramenta essencial para desenvolver as dinâmicas do jogo, destacando o controlo do ambiente sensorial.This study aimed to develop and validate a game strategy adapted to the rehabilitation of psychomotor function in a child with FOXP1, meeting the needs identified by the caregivers. A 4-years-old child with FOXP1 syndrome participated in this study. A semi-structured interview was conducted with the caregiver, which was transcribed and coded based on the International Classification of Functioning, Disability and Health (ICF). The Canadian Occupational Performance Measure was also implemented. An implementation testing of adapted rules of the Crazy Cups and Go Go Gelato analog games was conducted and components of a digital game were implemented. During these sessions it was recorded a video to allow qualitative and quantitative analysis of psychomotor behavior. The results showed that the components such as self-care, independence mobility in the community, general mobility, socialization and quiet recreation were highlighted as important for the caregiver, being modified by marked difficulties in motor organization and stimulus integration. There were differences in the number of interactions between the analog game and the digital game, highlighting the greater number of interactions in the digital game. It was also noticeable an evolution in the number of positive interactions from the first to the second session. This study contributed to the adaptation of games in the pediatric population. The caregiver's perspective is an essential tool to develop the game dynamics, highlighting the control of the sensory environment.El propósito de este estudio fue desarrollar y validar una estrategia de juego adaptada a la rehabilitación de la función psicomotora en un niño con FOXP1, que satisfaga las necesidades identificadas por los cuidadores. Un niño de 4 años con síndrome FOXP1 participó en este estudio. Se realizó una entrevista semiestructurada con el cuidador, que se transcribió y codificó según la Clasificación Internacional de Funcionamiento, Discapacidad y Salud (ICF). También se implementó la Medida de desempeño ocupacional canadiense. Posteriormente, se continuaron las pruebas de implementación adaptadas de los juegos analógicos Crazy Cups y Go Go Gelato. y componentes de un juego digital. Durante estas sesiones, se realizó una grabación de video para permitir el análisis cualitativo y cuantitativo del comportamiento psicomotor. Los resultados mostraron que los componentes como el autocuidado, la independencia del hogar, la movilidad, la socialización y la recreación tranquila se destacaron como importantes para el cuidador, siendo modificados por marcadas dificultades en la organización motora y la integración de estímulos. En la implementación de los juegos han sido idenitifacadas diferencias en el número de interacciones entre el juego analógico y el juego digital, destacando el mayor número de interacciones en el juego digital. También se observó una evolución en el número de interacciones positivas de la primera a la segunda sesión. Este estudio contribuyó a la adaptación de los juegos en la población pediátrica. La perspectiva del cuidador es una herramienta esencial para desarrollar la dinámica del juego, destacando el control del entorno sensorial. &nbsp

Regulation of biological paternity investigation: comparative perspective

O objetivo deste artigo analisar comparativamente a legisla o relativa investiga o de paternidade biológica de crianças nascidas fora do casamento no brasil e em países europeus, com base em pesquisa de documentos legislativos pela internet e na consulta de bibliografia jurídica no mbito do direito da família. Foi elaborada uma tipologia legislativa verdade biológica absoluta e verdade biológica relativa atendendo s seguintes variáveis: formas de atribui o da paternidade (voluntária/ordem do tribunal); tipo de consentimento exigido para realiza o do teste genético (voluntário/forçado); autor da investiga o (estado/outros); e limite temporal da investiga o (existência de prazos processuais/ausência de prazo processual). A verdade biológica absoluta ocorre quando a investigação de paternidade decorre obrigatoriamente, podendo ser ordenado e forçado pelo tribunal o recurso ao teste genético. observou-se a prevalência da verdade biológica relativa. Em todos os países analisados verificou-se que o recurso ao teste genético preponderante no estabelecimento das relações de filiação. Mesmo em países em que necessário o consentimento para a realização de teste de DNA existem modalidades de submiss o mais subtis, que incluem a aplicação de multas ou a gera o da presunção da paternidade com base na recusa em realizar exame genético.The aim of this article is to do a comparative analysis relative to the investigation of biological paternity of children born out of wedlock in Brazil and european countries, based on the research of legislative documents through the internet and the consultation of legal bibliography in the area of family law. The legislative typology was made - absolute biological truth and relative biological truth according to the following variables: forms of paternal attribution (voluntary/court ordered), type of demanded consent for the performance of the genetic test (voluntary/forced), author of the investigation (state/other) and the time limit of the investigation (existence of process deadlines/no process deadlines). The absolute biological truth occurs when the investigation of paternity is compulsory and the court might order and force the submission to a genetic test. The dominating trend is relative biological truth. In all analysed countries it has been verified that the resource to genetic testing is preponderant when establishing affiliation relations. Even in countries where it's not possible to force an individual to the submission of a genetic exam, there are more subtle ways of submission, that include the application of fines or the assumption of paternity based on a refusal to perform the genetic exam.info:eu-repo/semantics/publishedVersio

Violacein-Induced Chaperone System Collapse Underlies Multistage Antiplasmodial Activity

Antimalarial drugs with novel modes of action and wide therapeutic potential are needed to pave the way for malaria eradication. Violacein is a natural compound known for its biological activity against cancer cells and several pathogens, including the malaria parasite, Plasmodium falciparum (Pf). Herein, using chemical genomic profiling (CGP), we found that violacein affects protein homeostasis. Mechanistically, violacein binds Pf chaperones, PfHsp90 and PfHsp70-1, compromising the latter's ATPase and chaperone activities. Additionally, violacein-treated parasites exhibited increased protein unfolding and proteasomal degradation. The uncoupling of the parasite stress response reflects the multistage growth inhibitory effect promoted by violacein. Despite evidence of proteotoxic stress, violacein did not inhibit global protein synthesis via UPR activation - a process that is highly dependent on chaperones, in agreement with the notion of a violacein-induced proteostasis collapse. Our data highlight the importance of a functioning chaperone-proteasome system for parasite development and differentiation. Thus, a violacein-like small molecule might provide a good scaffold for development of a novel probe for examining the molecular chaperone network and/or antiplasmodial drug design.publishersversionpublishe

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

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children

IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).</jats:sec

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups