Externalização logística na área hospitalar : o caso de estudo Grupo Trofa Saúde

Tese de mestrado. Engenharia de Serviços e Gestão. Universidade do Porto. Faculdade de Engenharia. 201

POPULAÇÃO E BIOMASSA MICROBIANA EM SOLO DO PANTANAL MATOGROSSENSE

Este trabalho objetivou avaliar a população microbiana do solo em três áreas distintas, sendo elas, mata nativa, pastagem nativa e pastagem cultivada, no Pantanal mato-grossense. O solo foi coletado no mês de abril, final do período chuvoso, nas profundidades de 0-0,05 m, 0,05-0,1 m e 0,1-0,15 m. O número total de bactérias, actinomicetos e fungos cultiváveis foi maior na mata nativa, com destaque para o número de bactérias que diferiu estatisticamente das outras duas áreas. Na população de bactérias, as gram negativas e em formato de bastonete predominaram. O carbono da biomassa microbiana foi quantificado por dois métodos e em ambos os valores na mata nativa e pastagem nativa não diferiram entre si e foram superiores. Para a respiração basal a pastagem cultivada apresentou os menores valores. Este estudo demonstra que os solos da região pantaneira que ainda não sofreram alterações antrópicas conseguiram manter a população microbiana em franca atividade

Aripiprazole offsets mutant ATXN3-induced motor dysfunction by targeting dopamine D2 and serotonin 1A and 2A receptors in C. elegans

The atypical antipsychotic aripiprazole is a Food and Drug Administration-approved drug for the treatment of psychotic, mood, and other psychiatric disorders. Previous drug discovery efforts pinpointed aripiprazole as an effective suppressor of Machado–Joseph disease (MJD) pathogenesis, as its administration resulted in a reduced abundance and aggregation of mutant Ataxin-3 (ATXN3) proteins. Dopamine partial agonism and functional selectivity have been proposed as the main pharmacological mechanism of action of aripiprazole in the treatment of psychosis; however, this mechanism remains to be determined in the context of MJD. Here, we focus on confirming the efficacy of aripiprazole to reduce motor dysfunction in vivo, using a Caenorhabditis elegans (C. elegans) model of MJD, and on unveiling the drug targets required for its positive action against mutant ATXN3 pathogenesis. We employed pharmacogenetics and pharmacological approaches to identify which dopamine and serotonin receptors are critical for aripiprazole-mediated improvements in motor function. We demonstrated that dopamine D2-like and serotonin 5-HT1A and 5-HT2A receptors play important roles in this process. Our findings strengthen the relevance of dopaminergic and serotoninergic signaling modulation against mutant ATXN3-mediated pathogenesis. The identification of aripiprazole’s cellular targets, relevant for MJD and perhaps other neurodegenerative diseases, may pave the way for prospective drug discovery and development campaigns aiming to improve the features of this prototypical compound and reduce side effects not negligible in the case of aripiprazole.This work was funded by FEDER through the Competitiveness Internationalization Operational Program (POCI) and by National funds through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-0 31987, NORTE-01-0145-FEDER-000013, and NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement through the European Regional Development Fund (ERDF) and by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122; by National funds through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020). Additionally, this project was supported by the National Ataxia Foundation (NAF). A.J., J.P.-S., D.V.-C., and J.D.S. were supported by the FCT individual fellowships SFRH/BD/76613/2011, PD/BDE/127834/2016, SFRH/BD/147826/2019, and PD/BD/128074/2016, respectively

A National Wide Collaborative Study

INTRODUCTION: Even though the risk of COVID-19 in pregnancy may be increased, large-scale studies are needed to better understand the impact of the infection in this population. The aim of this study is to describe obstetric complications and the rate of vertical transmission in pregnant women with SARS-CoV-2 infection. MATERIAL AND METHODS: Detected cases of SARS-CoV-2 infection in pregnancy were registered in Portuguese hospitals by obstetricians. Epidemiological, pregnancy and childbirth data were collected. RESULTS: There were 630 positive cases in 23 Portuguese maternity hospitals, most at term (87.9%) and asymptomatic (62.9%). The most frequent maternal comorbidity was obesity. The rates of preterm birth and small-to-gestational-age were 12.1% and 9.9%, respectively. In the third trimester, 2.9% of pregnant women required respiratory support. There were eight cases (1.5%) of fetal death, including two cases of vertical transmission. There were five cases of postpartum respiratory degradation, but no maternal deaths were recorded. The caesarean section rate was higher in the first than in the second wave (68.5% vs 31.5%). RT-PCR SARS-CoV-2 positivity among newborns was 1.3%. CONCLUSION: SARS-Cov-2 infection in pregnancy may carry increased risks for both pregnant women and the fetuses. Individualized surveillance and the prophylaxis of this population with vaccination. is recommended in these cases.publishersversionepub_ahead_of_prin

Bovine herpesviruses do not play a major role in the differential diagnosis of rabies in cattle in Southern Brazil

Background: Rabies has long been recognized as the major cause of encephalitis in cattle in Latin American countries. It has been estimated that nearly 50.000 cattle heads per year are lost due to encephalitis in that subcontinent, with a signifi cant economic impact on cattle productive chains. In Brazil only, 2.500 to 3.000 cattle heads are estimated to be lost every year due to rabies. However, it is believed that rabies incidence in cattle is much larger, since usually only a few samples from affected animals in disease outbreaks are submitted to diagnostic laboratories. Rabies encephalitis is promptly and accurately diagnosed; however, particularly when rabies is excluded as causa mortis, the agent responsible for neurological disease of infectious origin often remains undetermined. Two bovine herpesviruses (BoHVs), bovine herpesvirus type 1 (BoHV-1) and bovine herpesvirus type 5 (BoHV-5) are major pathogens of cattle which are widely disseminated in Brazil. As usual in herpesvirus’ biology, these tend to infect a large number of hosts and establish lifelong latent infections which may occasionally be reactivated. Both viruses, particularly BoHV-5, are often recovered from cases of neurological disease in cattle. The participation of BoHVs in the differential diagnosis of rabies must be evaluated. Besides, there might be associations between the occurrence of rabies and BoHV infections that deserve investigation. The aim of this study was to investigate whether bovine herpesvirus 1 and 5 would play a signifi cant role in cases of neurological disease where rabies was the presumptive clinical diagnosis. In addition, associations between the occurrence of rabies and BoHV infections were searched for. The approach adopted for conducting such investigations was based on the search for viral nucleic acids as well as classical virus isolation on tissues of cattle submitted to rabies diagnosis over a two-year Materials, Methods & Results: Brain tissue samples of 101 cattle originally submitted to rabies diagnosis were collected over a two year period (2009-2010) from various municipalities within the state of Rio Grande do Sul, Brazil. Thirty nine of these samples had the diagnosis of rabies confi rmed by standard laboratory diagnostic methods. Aliquots of tissues were submitted to DNA extraction and examined in search for genomes of bovine herpesviruses (BoHV) types 1 (BoHV-1) and 5 (BoHV-5) by as well as for infectious virus. Bovine herpesvirus genomes were detected in 78/101 (77.2%) samples, in which BoHV-1 genomes were detected in 26/78 (25.7%), BoHV-5 genomes in 22/78 (21.8%) and mixed BoHV infections (BoHV-1 and BoHV-5 genomes) were detected in 30/101 (29.7%) samples. In the 39 samples with confi rmed rabies diagnosis, BoHV-1 DNA was detected in 9/39 (23%), BoHV-5 DNA in 6/39 (15.4%) and mixed infections with both BoHV types in 16/39 (41%) samples. However, no infectious herpesvirus was recovered from any of the specimens examined. Discussion: The high prevalence of BoHV1 and BoHV-5 infections was evidenced in the sampled population, but the absence of infectious BoHVs indicate that these were not associated to the occurrence of the cases of encephalitis where rabies was the primary suspicion. In addition, no association was detected between occurrence of rabies and detection of BoHVs, since the frequency of detection of herpesvirus genomes did not signifi cantly differ between rabies-positive and rabies-negative samples. The detection of BoHV DNA in scattered areas of the brain with no infectious virus suggests that latency may take place in different regions of the brain

Qualidade de vida em pacientes com fibrose cística

Introduction: Cystic Fibrosis (CF) is a rare, hereditary, multisystemic, and potentially lethal disease.Currently,with the advancement of medicine and the emergence of new therapies, CF patients are allowed to reach 40 years of age in developed countries.Objective: To assess the quality of life (QoL) ofpatients with CF to optimize their multidisciplinary care, based on criteria that impact their well-being. Material and Methods: Cross-sectional, prospective, quantitative, and exploratory study. Forty-seven interviews were collected from patients and their parents or legal guardians at a university referral center for CF in Minas Gerais, Brazil. The evaluation method was the Cystic Fibrosis Questionnaire (CFQ), associated with the analysis of the Shwachman-KulczyckiScore (SKS). Results: Our data showed that most of the CFQ domains were satisfactory (mean>50) and the SKS had good/excellent values ​​(score>71 points) in all groups. The group of patients older than 14 years had a worse QoL.Moreover, there was a divergence between the response of the 6 to 11 and 12 to 13-year group in comparison with the response of their legal guardians (p < 0.05). Conclusion: We found satisfactory means in all groups for the weight, digestive, and respiratory domains. However, the social role, vitality, emotional, and social domains had lower and decreasing means according to advancing age, then it would beparamount a multidisciplinary approach focused on these domains that most impact theirQoL. A limitation of research on rare diseases is the small sample, therefore not being possible to generalize the results. However, the analysis is still significant and relevant, demonstrating areas of impact that need to be improved.Introdução: A fibrose cística (FC) é uma doença rara, hereditária, multissistêmica e potencialmente letal. Atualmente, com o avanço da medicina e o surgimento de novas terapias, os pacientes com FC podem chegar aos 40 anos de idade em países desenvolvidos.Objetivo: Estudar a qualidade de vida dos pacientes com fibrose cística com o intuito de otimizar o atendimento multidisciplinar, baseando-se nos critérios que impactam seu bem-estar geral. Material e métodos: Estudo do tipo transversal, prospectivo, quantitativo e exploratório. Foram coletadas 47 entrevistas de pacientes e de seus responsáveis no centro de referência ao tratamento de fibrose cística de uma instituição pública de nível terciário. O método de avaliação foi o Cystic Fibrosis Questionnaire (CFQ), associado à análise do escore de Shwachman (SKS). Resultados: Nossos dados evidenciaram a maioria dos domínios do CFQ satisfatórios (média>50) e o SKS com valores bom/excelente (escore>71 pontos) em todos os grupos. O grupo de pacientes com mais de 14 anos apresentou pior QV, e houve uma divergência entre a resposta do grupo de 6 a 11 e 12 a 13 anos em relação à resposta dos seus pais e responsáveis (p<0,05). Conclusão: Encontramos médias satisfatórias em todos os grupos para os domínios peso, digestivo e respiratório. Porém, os domínios papel social, vitalidade, emocional e social apresentaram médias mais baixas e decrescentes com o avançar da idade, sendo essencial uma abordagem multidisciplinar focada nos domínios que mais impactam a qualidade de vida (QV). Uma limitação de pesquisas sobre doenças raras é a pequena amostra, não podendo, assim, generalizar os resultados. No entanto, a análise é significativa e relevante, demonstrando áreas de impacto e que devem ser aprimoradas

Promoting Responsible Research and Innovation (RRI) During Brazilian Activities of Genomic and Epidemiological Surveillance of Arboviruses

Zika infectio

Novel Machado-Joseph disease-modifying genes and pathways identified by whole-exome sequencing

Funding Information: This work was funded by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020 , and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia / Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/DTP-PIC/2638/2017 ( POCI-01-0145-FEDER-016592 ); GenomePT ( POCI-01-0145-FEDER-022184 ); ICVS Scientific Microscopy Platform , member of the national infrastructure PPBI - Portuguese Platform of Bioimaging ( PPBI-POCI-01-0145-FEDER-022122 ; by National funds , through the Foundation for Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020 ; and by the project NORTE-01-0145-FEDER-000013 , supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) . MR is supported by FCT ( CEECIND/03018/2018 ). ARVM ( SFRH/BD/129547/2017 ) and AFF ( SFRH/BD/121101/2016 ) are supported by a PhD grant financed by FCT . CB is supported by the Multiple System Atrophy Trust and Alzheimer's Research UK . MDC received funding from National Ataxia Foundation (NAF) and from FCT ( SFRH/BPD/101925/2014 ); DV-C received a grant from FCT ( SFRH/BD/147826/2019 ). Publisher Copyright: © 2021Machado-Joseph disease (MJD/SCA3) is a neurodegenerative polyglutamine disorder exhibiting a wide spectrum of phenotypes. The abnormal size of the (CAG)n at ATXN3 explains ~55% of the age at onset variance, suggesting the involvement of other factors, namely genetic modifiers, whose identification remains limited. Our aim was to find novel genetic modifiers, analyse their epistatic effects and identify disease-modifying pathways contributing to MJD variable expressivity. We performed whole-exome sequencing in a discovery sample of four age at onset concordant and four discordant first-degree relative pairs of Azorean patients, to identify candidate variants which genotypes differed for each discordant pair but were shared in each concordant pair. Variants identified by this approach were then tested in an independent multi-origin cohort of 282 MJD patients. Whole-exome sequencing identified 233 candidate variants, from which 82 variants in 53 genes were prioritized for downstream analysis. Eighteen disease-modifying pathways were identified; two of the most enriched pathways were relevant for the nervous system, namely the neuregulin signaling and the agrin interactions at neuromuscular junction. Variants at PARD3, NFKB1, CHD5, ACTG1, CFAP57, DLGAP2, ITGB1, DIDO1 and CERS4 modulate age at onset in MJD, with those identified in CFAP57, ACTG1 and DIDO1 showing consistent effects across cohorts of different geographical origins. Network analyses of the nine novel MJD modifiers highlighted several important molecular interactions, including genes/proteins previously related with MJD pathogenesis, namely between ACTG1/APOE and VCP/ITGB1. We describe novel pathways, modifiers, and their interaction partners, providing a broad molecular portrait of age at onset modulation to be further exploited as new disease-modifying targets for MJD and related diseases.publishersversionpublishe

Novel Machado-Joseph disease-modifying genes and pathways identified by whole-exome sequencing

Machado-Joseph disease (MJD/SCA3) is a neurodegenerative polyglutamine disorder exhibiting a wide spectrum of phenotypes. The abnormal size of the (CAG)n at ATXN3 explains ~55% of the age at onset variance, suggesting the involvement of other factors, namely genetic modifiers, whose identification remains limited. Our aim was to find novel genetic modifiers, analyse their epistatic effects and identify disease-modifying pathways contributing to MJD variable expressivity. We performed whole-exome sequencing in a discovery sample of four age at onset concordant and four discordant first-degree relative pairs of Azorean patients, to identify candidate variants which genotypes differed for each discordant pair but were shared in each concordant pair. Variants identified by this approach were then tested in an independent multi-origin cohort of 282 MJD patients. Whole-exome sequencing identified 233 candidate variants, from which 82 variants in 53 genes were prioritized for downstream analysis. Eighteen disease-modifying pathways were identified; two of the most enriched pathways were relevant for the nervous system, namely the neuregulin signaling and the agrin interactions at neuromuscular junction. Variants at PARD3, NFKB1, CHD5, ACTG1, CFAP57, DLGAP2, ITGB1, DIDO1 and CERS4 modulate age at onset in MJD, with those identified in CFAP57, ACTG1 and DIDO1 showing consistent effects across cohorts of different geographical origins. Network analyses of the nine novel MJD modifiers highlighted several important molecular interactions, including genes/proteins previously related with MJD pathogenesis, namely between ACTG1/APOE and VCP/ITGB1. We describe novel pathways, modifiers, and their interaction partners, providing a broad molecular portrait of age at onset modulation to be further exploited as new disease-modifying targets for MJD and related diseases