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Introduction: Basal cell carcinomas are mostly treated surgically, mostly by surgery with postoperative histopathologic margin evaluation (“conventional surgery”), but large long-term data regarding recurrence by completeness of excisions is limited. Methods: Retrospective cohort study of basal cell carcinomas treated by conventional surgery at different medical specialties in a large tertiary centre, between 2008 and 2014. Survival analysis with a Cox proportional-hazards was performed, stratified by completeness of excision (complete excision/incomplete excision) and adjusted to several potentially confounding covariates. Results: A total of 2876 basal cell carcinomas were identified, of which 2306 (2100 primary, 206 recurrent) were considered eligible for analysis. During the 5-years of follow-up, there were 80 (4%) recurrences among 1980 complete excisions (16/1000 cases-year) and 83 (23.9%) recurrences among 348 incomplete excisions (100/1000 cases-year). Survival analysis was performed with multivariable adjustment. In the final adjusted model, we identified an association between relapse and re-intervention on recurrent tumors [adjusted Hazard Ratio (HR) 2.20 (95% Confidence interval (IC), 1.26-3.84), p=0.006], a wrong preoperative clinical diagnosis/surgery devoid of preoperative biopsy [adjusted HR 2.75 (95% CI, 1.68-4.5), p

Indivíduos diagnosticados com Transtorno do Espectro do Autismo (TEA) apresentam comprometimento qualitativo para interagir socialmente de forma recíproca, para discriminar o sentido social das experiências com outros e, por conseguinte, prejuízo significativo no processo de desenvolvimento de habilidades sociocomunicativas. Sinais de autismo podem ser identificados desde o primeiro ano de vida, o que representa possibilidade de iniciar intervenção precoce – sendo esta um importante preditor na recuperação funcional desse transtorno do neurodesenvolvimento. O objetivo do presente estudo é revisar, na literatura científica, procedimentos de intervenção comportamentais e de desenvolvimento intensivas e precoce, em crianças diagnosticadas com TEA, que revelem evidência de resultados. Foram pesquisadas cinco bases de dados internacionais, nas áreas de saúde e educação, como fontes da busca, quais sejam: a) Web of Science; b) Scopus; c) PsycInfo; d) Eric; e, e) BVS. A partir disso, foram selecionados 95 artigos a partir dos critérios de inclusão adotados e identificou-se que as principais áreas de desenvolvimento-alvos das intervenções são habilidades de comunicação, interação social e cognição; o tempo médio pode variar, contudo, a recomendação é de que haja intensidade de, no mínimo, 3 horas por dia; os contextos de intervenção variam e envolvem predominantemente ambientes clínicos ou domésticos, cujos agentes de intervenção são técnicos e pais. Quanto aos ingredientes ativos nos efeitos das intervenções, quanto mais nova a criança e mais alto for o QI, maior a probabilidade de desfechos favoráveis na intervenção; em relação aos principais indicadores de qualidade, os programas são avaliados a partir de ganhos nas habilidades cognitivas, de linguagem, adaptativas e sociais. Tais resultados podem ser convertidas em diretrizes na implementação de programas de intervenção precoce para crianças com autismo.

Background and objectives To understand how organisms evolve, it is fundamental to study how mutations emerge and establish. Here, we estimated the rate of mutation accumulation of SARS-CoV-2 in vitro and investigated the repeatability of its evolution when facing a new cell type but no immune or drug pressures. Methodology We performed experimental evolution with two strains of SARS-CoV-2, one carrying the originally described spike protein (CoV-2-D) and another carrying the D614G mutation that has spread worldwide (CoV-2-G). After 15 passages in Vero cells and whole genome sequencing, we characterized the spectrum and rate of the emerging mutations and looked for evidences of selection across the genomes of both strains. Results From the frequencies of the mutations accumulated, and excluding the genes with signals of selection, we estimate a spontaneous mutation rate of 1.3 × 10−6 ± 0.2 × 10−6 per-base per-infection cycle (mean across both lineages of SARS-CoV-2 ± 2SEM). We further show that mutation accumulation is larger in the CoV-2-D lineage and heterogeneous along the genome, consistent with the action of positive selection on the spike protein, which accumulated five times more mutations than the corresponding genomic average. We also observe the emergence of mutators in the CoV-2-G background, likely linked to mutations in the RNA-dependent RNA polymerase and/or in the error-correcting exonuclease protein. Conclusions and implications These results provide valuable information on how spontaneous mutations emerge in SARS-CoV-2 and on how selection can shape its genome toward adaptation to new environments. Lay Summary: Each time a virus replicates inside a cell, errors (mutations) occur. Here, via laboratory propagation in cells originally isolated from the kidney epithelium of African green monkeys, we estimated the rate at which the SARS-CoV-2 virus mutates—an important parameter for understanding how it can evolve within and across humans. We also confirm the potential of its Spike protein to adapt to a new environment and report the emergence of mutators—viral populations where mutations occur at a significantly faster rate.

Even though tourists increasingly value sustainable practices in tourism businesses and destinations, price is still one of the main determinant factors in their decisions. Therefore, for destination managers it is essential to understand tourists’ willingness to pay an additional price to visit a place where sustainable practices are adopted. In this context, and building on social psychology theories, the present study proposes and tests a causal model encompassing tourists’ Willingness To Pay (WTP) for sustainability in tourist destinations as well as their own sustainability attitudes, namely: Environmental Beliefs, Ecotour Attitudes, and Sustainable Consumption Behaviour. To this end, data were collected through a questionnaire survey of Portuguese tourists (n = 567). The hypothesised relationships between the latent variables were then tested using Structural Equations Modelling (SEM) procedures. The results show that Environmental Beliefs significantly affected both Ecotour Attitudes and Sustainable Consumption Behaviour, and that the latter two significantly affected WTP. However, no significant effect of Environmental Beliefs on WTP was found. These findings provide useful insights for destination managers aiming to more effectively cater to sustainability-oriented tourists. Future research should attempt to assess the role of other determinants of WTP.

IntroductionInformation on vaccine effectiveness and viral loads in a context of novel variants of concern (VOC) emergence is of key importance to inform public health policies. This study aimed to estimate a measure of comparative vaccine effectiveness between Omicron (BA.1) and Delta (B.1.617.2 and sub-lineages) VOC according to vaccination exposure (primary or booster) and time since primary vaccination and to compare cycle threshold (Ct) values between Omicron and Delta VOC infections according to the vaccination status as an indirect measure of viral load.MethodsWe developed a case-case study using data on RT-PCR SARS-CoV-2 positive cases notified in Portugal during weeks 49-51 2021. The odds of vaccination in Omicron cases were compared to Delta using logistic regression adjusted for age group, sex, region and week of diagnosis and laboratory of origin. RT-PCR Ct values were compared by vaccination status and variant using linear regression model.ResultsHigher odds of vaccination were observed in cases infected by Omicron (BA.1) VOC compared to Delta (B.1.617.2) VOC cases for both complete primary vaccination (OR=2.1; CI 95% :1.8 to 2.4) and booster dose (OR= 5.2; CI 95%: 3.1 to 8.8), indicating vaccine effectiveness reduction against Omicron. No differences in distribution of Ct-values between these two VOC were observed for any vaccination exposure categories.ConclusionConsistent lower VE was observed against Omicron infection. Complete primary vaccination may not be protective against SARS-CoV-2 infection in regions where Omicron variant is dominant, but a massive rollout of booster vaccination campaign can contribute to reduce SARS-CoV-2 incidence in the population.

The quality of the coparental relationship after parental divorce significantly affects the parent-child relationship and the child development. Aiming to analyze the recent scientific literature on the relationship between coparenting and child behavior in divorced families, a systematic review was conducted according to the methodological recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA). The searches were carried out in six national and international databases, using the words coparenting, divorce and child behavior, and similar terms, in Portuguese, English and Spanish. Eleven articles published between 2010 and June 2020 were included. The main results of the studies showed that coparental support after divorce favors more positive outcomes in child behavior. On the other hand, the existence of coparental conflict represents risk factor for child behavioral problems, including in families whit coparental support and communication exist. La calidad de la relación coparental después del divorcio de los padres afecta significativamente la relación entre padres e hijos y el desarrollo infantil. A fin de analizar la literatura científica reciente sobre la relación entre coparentalidad y comportamiento del niño en familias divorciadas, se realizó una revisión sistemática conforme las recomendaciones metodológicas del Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Las búsquedas se realizaron en seis bases de datos, nacionales e internacionales, con los términos coparentalidad, divorcio y comportamiento infantil en portugués, inglés y español. Se incluyeron 11 artículos publicados entre 2010 y junio de 2020. Los principales resultados de los estudios mostraron que el apoyo coparental después del divorcio favorece resultados más positivos en el comportamiento infantil. Sin embargo, la existencia de conflicto coparental representa factor de riesgo para problemas de comportamiento en niños, incluso en familias que existe el apoyo y la comunicación coparental. A qualidade da relação coparental após o divócio dos pais afeta significativamente a relação pai-filhos e o desenvolvimento infantil. Com o objetivo de analisar a literatura científica recente a respeito das relações entre coparentalidade e comportamento da criança em famílias divorciadas, conduziu-se uma revisão sistemática de acordo com as recomendações metodológicas do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). As buscas foram realizadas em seis bases de dados, nacionais e internacionais,com os termos coparentalidade, divórcio e comportamento da criança, e termos correlatos, em português, inglês e espanhol. Foram incluídos 11 artigos publicados entre 2010 e junho de 2020. Por meio da análise dos resultados desses artigos, constatou-se que o apoio coparental após o divórcio favorece desfechos positivos no comportamento infantil. Por outro lado, a existência de conflito coparental representa fator de risco para problemas de comportamento na criança, inclusive em famílias onde há apoio e comunicação coparental.

IntroductionThe B.1.617.2 variant (Delta) was associated with increased transmissibility and lower vaccine effectiveness than the B.1.1.7 variant (Alpha). However, the effect of the B.1.617.2 variant on disease severity remains unclear. This study aims to assess whether infection with the B.1.617.2 variant was associated with a higher risk of serious illness, compared with other co-circulating variants, measured through hospitalization and death by COVID-19 in Portugal.MethodsWe conducted a matched cohort study in adult individuals diagnosed with SARS-CoV-2/COVID-19 infection between March 29 and August 1, 2021. Cases were individuals with a positive PCR test notified to the surveillance system. SARS-CoV-2 variants were classified first by genomic sequencing (WGS) and, if this information was unavailable, by detecting the S gene target failure.Delta (B.1.617.2) and Alpha (B.1.1.7) cases were matched on the week of diagnosis at a 1 to k ratio (k being the maximum number of unexposed available in that week) to maximize the inclusion of unexposed, using the nearest-neighbor algorithm. The hazard risk and 95% confidence intervals of hospitalization and death among those infected with the Delta (B.1.617.2) variant vs. Alpha (B.1.1.7) was estimated using a Cox proportional hazards model, adjusting for confounding for sex, age, and vaccination status.ResultsA total of 2,778 cases were included in the study. Of the total, 1 742 (68%) were identified as B.1.617.2 variant cases and 3 629 (32%) as B.1.1.7 variant. Within the B.1.1.7 variant cases 106 (2.9%) were hospitalized, and 110 (6.3%) within the B.1.617.2 variant cases. A total of 29 deaths were reported, 8 (0.2%) in patients infected with B.1.1.7 variant and 21 (1.2%) in patients with the B.1.617.2 variant. The confounding adjusted risk of hospitalization, in persons infected with the B.1.617.2 variant was 2.44 (95%CI 1.85; 3.20) times higher than the risk of hospitalization among B.1.1.7 variant cases, and the confounding-adjusted risk of death for B.1.617.2 variant cases was 5.20 (95%CI 2.20; 12.29) times higher than the risk of death in patients infected by B.1.1.7 variant.ConclusionThe B.1.617.2 variant is associated with an increased risk of hospitalization and death compared with the B.1.1.7 variant.

IntroductionEarly reports showed that Omicron (BA.1) SARS-CoV-2 could be less severe. However, the magnitude of risk reduction of hospitalization and mortality of Omicron (BA.1) infections compared with Delta (B.1.617.2) is not yet clear. This study compares the risk of severe disease among patients infected with the Omicron (BA.1) variant with patients infected with Delta (B.1.617.2) variant in Portugal.MethodsWe conducted a cohort study in individuals diagnosed with SARS-CoV-2 infection between 1stand 29thDecember 2021. Cases were individuals with a positive PCR test notified to the national surveillance system. SARS-CoV-2 variants were classified first by whole genomic sequencing (WGS) and, if this information was unavailable, by detecting the S gene target failure. We considered a hospitalization for all the patients admitted within the 14 days after the SARS-CoV-2 infection; after that period, they were censored.The comparison of the risk of hospitalization between Omicron (BA.1) and Delta (B.1.617.2) VOC was estimated using a Cox proportional hazards model. The mean length of stay was compared using linear regression, and the risk of death between Omicron and Delta patients was estimated with a penalized logistic regression. All models were adjusted for sex, age, previous infection, and vaccination status.ResultsWe included 15 978 participants aged 16 or more years old, 9 397 infected by Delta (B.1.617.2) and 6 581 infected with Omicron (BA.1). Within the Delta (B.1.617.2) group, 148 (1.6%) were hospitalized, and 16 (0.2%) were with the Omicron (BA.1). A total of 26 deaths were reported, all in participants with Delta (B.1.617.2) infection. Adjusted HR for hospitalization for the Omicron (BA.1) variant compared with Delta (B.1.617.2) was 0.25 (95%CI 0.15 to 0.43). The length of stay in hospital for Omicron (BA.1) patients was significantly shorter than for Delta (confounding-adjusted difference -4.0 days (95%CI -7.2 to -0.8). The odds of death were 0.14 (95% CI 0.0011 to 1.12), representing a reduction in the risk of death of 86% when infected with Omicron (BA.1) compared with Delta (B.1.617.2).ConclusionOmicron (BA.1) was associated with a 75% risk reduction of hospitalization compared with Delta (B.1.617.2) and reduced length of hospital stay.

In the last years, “omics” approaches have been applied to study the toxicity of nanomaterials (NM) with the aim of obtaining insightful information on their biological effects. One of the most developed “omics” field, transcriptomics, expects to find unique profiles of differentially expressed genes after exposure to NM that, besides providing evidence of their mechanistic mode of action, may also be used as biomarkers for biomonitoring purposes. Moreover, several NM have been associated with epigenetic alterations, i.e., changes in the regulation of gene expression caused by differential DNA methylation, histone tail modification and microRNA expression. Epigenomics research focusing on DNA methylation is increasingly common and the role of microRNAs is being better understood, either promoting or suppressing biological pathways. Moreover, the proteome is a highly dynamic system that changes constantly in response to a stimulus. Therefore, proteomics can identify changes in protein abundance and/ or variability that lead to a better understanding of the underlying mechanisms of action of NM while discovering biomarkers. As to genomics, it is still not well developed in nanotoxicology. Nevertheless, the individual susceptibility to NM mediated by constitutive or acquired genomic variants represents an important component in understanding the variations in the biological response to NM exposure and, consequently, a key factor to evaluate possible adverse effects in exposed individuals. By elucidating the molecular changes that are involved NM toxicity, the new “omics” studies are expected to contribute to exclude or reduce the handling of hazardous NM in the workplace and support the implementation of regulation to protect human health. This work was funded by FCT/ MCTES, project PTDC/SAU-PUB/32587/2017 and project PTDC/BTM-TEC/28554/2017 through national funds (PIDDAC), ToxOmics (UIDB/00009/2020; UIDP/00009/2020) and BioISI—Biosystems & Integrative Sciences Institute, Faculty of Sciences University of Lisbon, Lisbon, Portugal. It is also a result of 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 FCT, and the National Mass Spectrometry Network (RNEM)-FCT Infrastructure Program, Portugal. info:eu-repo/semantics/publishedVersion

One of the most important livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) genetic lineages is the clonal complex (CC) 398, which can cause typical S. aureus-associated infections in people. In this work, whole-genome sequencing, RNA-sequencing, and gel-based comparative proteomics were applied to study the genetic characteristics of three MRSA CC398 isolates recovered from humans (strains C5621 and C9017), and from an animal (strain OR418). Of the three strains, C9017 presented the broadest resistance genotype, including resistance to fluroquinolone, clindamycin, tiamulin, macrolide and aminoglycoside antimicrobial classes. The scn, sak, and chp genes of the immune evasion cluster system were solely detected in OR418. Pangenome analysis showed a total of 288 strain-specific genes, most of which are hypothetical or phage-related proteins. OR418 had the most pronounced genetic differences. RNAIII (δ-hemolysin) gene was clearly the most expressed gene in OR418 and C5621, but it was not detected in C9017. Significant differences in the proteome profiles were found between strains. For example, the immunoglobulin-binding protein Sbi was more abundant in OR418. Considering that Sbi is a multifunctional immune evasion factor in S. aureus, the results point to OR418 strain having high zoonotic potential. Overall, multiomics biomarker signatures can assume an important role to advance precision medicine in the years to come. SIGNIFICANCE: MRSA is one of the most representative drug-resistant pathogens and its dissemination is increasing due to MRSA capability of establishing new reservoirs. LA-MRSA is considered an emerging problem worldwide and CC398 is one of the most important genetic lineages. In this study, three MRSA CC398 isolates recovered from humans and from a wild animal were analyzed through whole-genome sequencing, RNA-sequencing, and gel-based comparative proteomics in order to gather systems-wide omics data and better understand the genetic characteristics of this lineage to identify distinctive markers and genomic features of relevance to public health. This work was supported by the Associate Laboratory for Green Chemistry-LAQV, which is financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020) and by the projects UIDB/CVT/00772/2020 and LA/P/0059/2020 funded by the Portuguese Foundation for Science and Technology (FCT). H. S. acknowledges the Associate Laboratory for Green Chemistry-LAQV (LA/P/0008/2020) funded by Fundação para a Ciência e a Tecnologia, I.P for his research contract. This work is a result of the GenomePT project (POCI-01-0145- FEDER-022184), supported by COMPETE 2020 - Operational Pro gramme for Competitiveness and Internationalization (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/publishedVersion

The infestation of Rhipicephalus microplus (Acari: Ixodidae) (Canestrini, 1887) represents a significant health problem for cattle. Up until today, no consistent control has been recommended for the free-living larval stage of R. microplus. The objective of the present study was to determine the larvicidal effect of an Allium sativum (garlic) aqueous extract against R. microplus using the larval package test, LPT. Tick larvae were obtained from adult female ticks from naturally infected animals, and 200 larvae were exposed to each A. sativum extract concentration (5, 7, 10, 16, 25, and 50%). All garlic groups received the extract in three different volumes (2, 5, and 7 ml) to determine the levels of humidity that would affect the free-living stage. Larvae from the control group were treated with distilled water and the positive control used cypermethrin in a 5-ml volume. Live and dead larvae were determined after 24 h of exposure. There was a significant statistical difference (P = 0.041) at 5% between 2 and 5 ml and between 7 and 10% of the extract using 2 ml (P = 0.034). There was a significant larvicidal activity of 100% mortality for the 16, 25, and 50% concentrations for all volumes. We observed a clear concentration-dependent effect for the extracts with a correlation coefficient of R

O presente artigo tem como objetivo comparar, por meio da histomorfometria, os alvéolos frescos enxertados com Fibrina Rica em Plaquetas e Leucócitos (L-PRF) com os alvéolos frescos convencionais contendo apenas coágulo sanguíneo. Procurou-se averiguar se existe diferença na formação óssea ao se adicionar a L-PRF no alvéolo pós-extração dentária, para garantir melhor formação óssea para posterior reabilitação por implantes osseointegrados. Foi realizado um estudo de boca dividida (split mouth), em um paciente (estudo piloto). Realizou-se no lado esquerdo a exodontia do 36 e 37 e, em seguida, enxertias com as membranas de L-PRF e, no lado direito, foi realizada exodontia do 46 e 47 deixando o alvéolo reparar livremente sem enxertia (apenas com coágulo sanguíneo convencional). Após 2 meses, foi realizada a cirurgia de instalação dos implantes dentários. Nesta etapa foi possível coletar 4 (quatro) amostras para análise histomorfométrica das diferentes regiões estudadas. Houve uma diferença com resultados melhores para o lado enxertado com L-PRF, sendo um reparo ósseo de 70%, 65%, 60% e 60% respectivamente para a região dos dentes 36, 37, 46 e 47. Para este estudo piloto foi possível afirmar que o lado teste apresentou uma melhor formação óssea quando comparado ao lado controle, indicando que pesquisas com amostragem adequada para análises estatísticas deverão ser realizadas dentro da metodologia proposta.

Made available in DSpace on 2022-04-28T16:56:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-13. Added 1 bitstream(s) on 2022-04-28T17:11:46Z : No. of bitstreams: 1 S1414-98932021000700200.pdf: 80501 bytes, checksum: 804e5d49a7d4147972d5081d6e0dd2d0 (MD5) Universidade Federal do Rio Grande do Sul Universidade Estadual Paulista Júlio de Mesquita Filho Universidade Federal de Santa Catarina Universidade Estadual Paulista Júlio de Mesquita Filho

O Gatekeeping materno é um fator importante para avaliar a proximidade e qualidade da relação do pai com os filhos. Este consiste em crenças e comportamentos maternos que podem facilitar ou dificultar o envolvimento paterno com a criança. Dentre vários fatores que afetam esses comportamentos maternos encontra-se a personalidade do pai. Como poucos estudos investigaram a relação entre estas variáveis, esta pesquisa objetivou comparar as percepções de pais e mães do gatekeeping materno e investigar os efeitos da percepção paterna de sua personalidade nas percepções materna e paterna do gatekeeping da mãe em famílias com crianças de quatro a seis anos. Participaram 171 casais do Sul do Brasil que responderam ao Questionário de Gatekeeping Materno e Inventário dos Cinco Grandes Fatores de Personalidade. Os resultados apontaram níveis moderados de gatekeeping materno, e elevados níveis de conscienciosidade e amabilidade paterna. As análises comparativas indicaram que pais perceberam maiores níveis de confirmação da identidade materna em comparação às próprias mães, e as mães perceberam em maior nível que os pais que tarefas domésticas e cuidados com as crianças fazem parte do papel materno. A regressão linear múltipla indicou que quanto mais neuroticismo, maior foi a percepção paterna do controle materno pelas normas e responsabilidades domésticas; e quanto mais extroversão, menos as mães relataram realizar o controle pelas normas e responsabilidades domésticas. Reforça-se a relação entre características pessoais em interação com construções histórico-sociais de gênero que afetam crenças e comportamentos maternos sobre tarefas domésticas e cuidados infantis, influenciando o envolvimento paterno.

Highlights • Deciduosis is defined as the presence of decidual tissue in an ectopic location. • It is caused by progesterone-mediated metaplasia of mesenchymal cells. • We describe a case of a non-pregnant patient with extensive peritoneal spread. • As in this report, this entity might mimic oncological conditions., Ectopic decidual reaction (or deciduosis) can be rarely seen in the peritoneum and most of the cases in the literature are associated with pregnancy. It is more commonly found in the ovaries, uterus and cervix. Although its pathophysiology is not totally understood, it is accepted that peritoneal deciduosis develops as a result of the progesterone induced metaplasia of subserosal stromal cells during pregnancy. It is important to distinguish this entity from oncologic conditions, namely metastatic carcinoma and mesothelioma. We report an unusual case of a 40 year-old non pregnant patient that presented with imaging findings suggestive of peritoneal carcinomatosis.

Recent studies have shown that persistent SARS-CoV-2 infections in immunocompromised patients can trigger the accumulation of an unusual high number of mutations with potential relevance at both biological and epidemiological levels. Here, we report a case of an immunocompromised patient (non-Hodgkin lymphoma patient under immunosuppressive therapy) with a persistent SARS-CoV-2 infection (marked by intermittent positivity) over at least 6 months. Viral genome sequencing was performed at days 1, 164, and 171 to evaluate SARS-CoV-2 evolution. Among the 15 single-nucleotide polymorphisms (SNPs) (11 leading to amino acid alterations) and 3 deletions accumulated during this long-term infection, four amino acid changes (V3G, S50L, N87S, and A222V) and two deletions (18-30del and 141-144del) occurred in the virus Spike protein. Although no convalescent plasma therapy was administered, some of the detected mutations have been independently reported in other chronically infected individuals, which supports a scenario of convergent adaptive evolution. This study shows that it is of the utmost relevance to monitor the SARS-CoV-2 evolution in immunocompromised individuals, not only to identify novel potentially adaptive mutations, but also to mitigate the risk of introducing "hyper-evolved" variants in the community. IMPORTANCE Tracking the within-patient evolution of SARS-CoV-2 is key to understanding how this pandemic virus shapes its genome toward immune evasion and survival. In the present study, by monitoring a long-term COVID-19 immunocompromised patient, we observed the concurrent emergence of mutations potentially associated with immune evasion and/or enhanced transmission, mostly targeting the SARS-CoV-2 key host-interacting protein and antigen. These findings show that the frequent oscillation in the immune status in immunocompromised individuals can trigger an accelerated virus evolution, thus consolidating this study model as an accelerated pathway to better understand SARS-CoV-2 adaptive traits and anticipate the emergence of variants of concern. This study was partially cofunded 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 Program (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/publishedVersion

We report a multidrug resistant Neisseria gonorrhoeae exhibiting resistance to ceftriaxone and cefixime, isolated in Portugal in 2019. Whole-genome sequencing was performed for typing and identification of genetic determinants of antimicrobial resistance. Due to its antimicrobial susceptibility profile, awareness should be raised for the circulation of this strain. M.P. was supported by the Portuguese Science and Technology Foundation through grant SFRH/BD/109264/2015. info:eu-repo/semantics/publishedVersion

O objetivo deste estudo foi identificar a produção de artigos científicos envolvendo a importância da brinquedoteca para o desenvolvimento infantil da criança hospitalizada, publicados em âmbito nacional entre 2008 até abril de 2018. Utilizou-se os descritores “brinquedo”, “hospital” e “criança” nas seguintes bases de dados: IndexPsi, SciELO, PePSIC, LILACS e Periódicos CAPES . Obteve-se o total de 151 resultados. Após leitura integral dos artigos, a amostra consistiu em 10 artigos científicos. Realizou-se uma análise sistemática dos achados, levantando seis categorias temáticas: 1) continuidade no desenvolvimento infantil; 2) humanização do atendimento; 3) interação social; 4) alívio dos efeitos emocionais decorrentes da internação; 5) o lúdico como fator de aprendizagem; e 6) distração. A brinquedoteca, vista a partir da Psicologia Ambiental, é um importante ambiente restaurador que possibilita a humanização do cuidado e traz benefícios não somente para a criança, mas também para os profissionais da saúde e acompanhantes.

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31950026/ Gastrointestinal infections caused by nontyphoidal Salmonella (NTS) remain one of the main causes of foodborne illness worldwide. Within the multiple existing Salmonella enterica serovars, the serovar Rissen is rarely reported, particularly as a cause of human salmonellosis. Between 2015 and 2017, the Portuguese National Reference Laboratory of Gastrointestinal Infections observed an increase in the number of clinical cases caused by multidrug-resistant (MDR) S. enterica serovar Rissen, particularly from the Azores archipelago. In the present study, we analyzed by whole genome sequencing (WGS) all clinical, animal, food, and environmental isolates received up to 2017 in the Portuguese Reference Laboratories. As such, through a wgMLST-based gene-by-gene analysis, we aimed to identify potential epidemiological clusters linking clinical and samples from multiple sources, while gaining insight into the genetic diversity of S. enterica serovar Rissen. We also investigated the genetic basis driving the observed multidrug resistance. By integrating 60 novel genomes with all publicly available serovar Rissen genomes, we observed a low degree of genetic diversity within this serovar. Nevertheless, the majority of Portuguese isolates showed high degree of genetic relatedness and a potential link to pork production. An in-depth analysis of these isolates revealed the existence of two major clusters from the Azores archipelago composed of MDR isolates, most of which were resistant to at least five antimicrobials. Considering the well-known spread of MDR between gastrointestinal bacteria, the identification of MDR circulating clones should constitute an alert to public health authorities. Finally, this study constitutes the starting point for the implementation of the "One Health" approach for Salmonella surveillance in Portugal. This work was partially funded by 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), and Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by the Fundação para a Ciência e a Tecnologia (FCT) info:eu-repo/semantics/publishedVersion

The aim of this study was to identify the production of scientific articles involving the importance of the toy library for the child development of hospitalized children, published nationwide between 2008 and April 2018. The keywords "toy", "hospital" and "child" were used in the databases: IndexPsi (06), SciELO (21), PePSIC (04), LILACS (60) and CAPES Journals (60). A total of 151 results were obtained. After applying inclusion and exclusion criteria, the sample consisted of 10 scientific papers. A systematic analysis of the findings was carried out, raising six thematic categories that contemplate the main contributions of the hospital toy library: 1) continuity in the child development; 2) humanization of care; 3) social interaction; 4) relief of the emotional effects of hospitalization; 5) the playful as a learning factor; and 6) distraction. It was agreed that the toy library is an environment that enables the humanization of care and brings benefits to the child, professionals and caregivers.

The aim of this review was to analyze the empirical studies that have measured temperament and coparenting. Accordingly, we sought to answer the question: “What is the relationship between the variables of coparenting and temperament in empirical studies, considering the different theoretical approaches, the different instruments used and families with children between zero and 11 years of age?” The databases chosen for this review were VHL-Psi, PsycINFO, PubMed, Scopus and Web of Science. The VHL-Psi database was searched, however, no articles were found. A total of 28 articles were selected, which were analyzed in their entirety and described regarding the number of participants, method, instruments used and other variables measured. The results regarding the relationship between coparenting and temperament were organized into six categories. Only two articles indicated a lack of significant relationships between the two variables. Temperament as a predictor of coparenting and the moderating role of coparenting as a risk and protection factor were highlighted. Bidirectional relationships between variables were addressed in only three articles and the lack of studies in this direction was evident. Differences in the coparenting of fathers and mothers highlight the importance of gender discussions.

Resumo Objetivo: Analisar sistematicamente a produção científica acerca do apego e a parentalidade sob o enfoque transcultural. Método: Realizou-se o levantamento de produções indexadas, a partir de buscas em bases de dados nacionais -Scielo Brasil- e CAPES -Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-; e internacionais -PsycINFO-, mediante os seguintes descritores: Apego OR Bowlby AND parentalidade OR “relação parental”; Attachment OR Bowlby AND Parenting OR Parenthood; e por fim, Apego OR Bowlby AND Parentalidad OR “Relaciones parentales”. Foram considerados os estudos nos idiomas português, inglês e espanhol, entre o período de 2013 a outubro de 2017. Após a definição dos critérios de inclusão, os cinco artigos retidos foram analisados com base nos aspectos metodológicos (dados da amostra, tipo de abordagem, tipo de estudo e técnica de coleta de dados), e posteriormente, foram submetidos a análise semântica, da qual derivou-se duas categorias temáticas: 1) Fatores que influenciam a formação do apego e a parentalidade e 2) Apego e relações parentais. Resultados: Apontaram-se lacunas existentes no que se refere à produção científica especificamente ao tema elencado; tendo em vista a diversidade de estudos que englobam os sistemas de apego e temas transversais, como apego e desenvolvimento infantil, apego e psicopatologia, apego e maternidade, entre outros. Além disso, não foram encontrados estudos nacionais sobre a temática, assim como pesquisas transculturais a respeito. Em relação ao delineamento dos estudos encontrados, todos caracterizam-se pelo enfoque quantitativo e estudos longitudinais do tipo prospectivosfollow-up. As técnicas de coleta de dados que mais se sobressaíram foram a Entrevista de Apego Adulto (AAI), seguida da Situação Estranha em pesquisas com amostras infantis. Conclusão: Destaca-se que a Teoria do Apego necessita estar aberta para a revisão e a consideração das dimensões relacionadas à cultura. Isso implica ajustá-la à diferentes contextos culturais, históricos e sociais. Sugere-se, portanto, o incremento de novos estudos que contemplem a formação do apego, os quais venham disseminar intervenções parentais positivas para o ciclo de vida pessoal e familiar dos sujeitos. Abstract Objective: This paper aims to analyze systematically the scientific production related to attachment behavioral and parenting based on a cross-cultural approach. Method: A survey of indexed productions based on national databases such as: Scielo Brasil and CAPES -Coordination of Improvement of Higher Level Personnel-; and international -PsycINFO-, using the following descriptors: Apego OR Bowlby AND parenting OR “parental relationship”; Attachment OR Bowlby AND Parenting OR Parenthood; and finally, Apego OR Bowlby AND Parentality OR “Parental relationships” was performed. Studies translated into Portuguese, English and Spanish between 2013 and October 2017 were considered. After defining the inclusion criteria, the five retained articles were analyzed based on the methodological aspects (sample data, type of approach, type of study and data collection technique), and afterwards, they were submitted to semantic analysis, from which we derived two thematic categories: 1) Factors that influence the formation of attachment and parenting, and 2) Attachment and parental relationships. Results: Gaps corresponding to the scientific production according to the topics suggested were identified; identifying the diversity of studies related to attachment behavioral systems and cross-cutting themes, such as: child attachment behavioral and development, attachment behavioral and psychopathology, attachment behavioral and motherhood, among others, were taken into account. In addition, there is no national studies based on these topics, as well as cross-cultural surveys. A quantitative approach and prospective longitudinal studies (follow-up) were conducted in these studies. In order to collect the data, Adult Attachment Interview (AAI) followed by The Strange Situation Survey used with children sampled, were highlighted. Conclusion: It should be noted that the Theory of Attachment needs to be open to the review and consideration of dimensions related to culture. This implies adjusting it to different cultural, historical and social contexts. It is suggested, therefore, the increase of new studies that contemplate the formation of attachment, which will disseminate positive parental interventions for the individuals’ personal and family life cycle. Resumen Objetivo: Analizar sistemáticamente la producción científica acerca del apego y la parentalidad bajo el enfoque transcultural. Método: Se realizó el levantamiento de producciones indexadas a partir de búsquedas en bases de datos nacionales -Scielo Brasil- y CAPES -Coordinación de Perfeccionamiento de Personal de Nivel Superior-; e internacionales -PsycINFO-, mediante los siguientes descriptores: Apego OR Bowlby AND parentalidad OR “relación parental”. Y por último, Apego OR Bowlby AND Parentalidad OR “Relaciones parentales”. Se consideraron los estudios en portugués, inglés y español, entre el período de 2013 a octubre de 2017. Después de la definición de los criterios de inclusión, los cinco artículos retenidos se analizaron sobre la base de los aspectos metodológicos (datos de la muestra, tipo de enfoque, tipo de estudio y técnica de recolección de datos), y posteriormente se sometieron al análisis semántico; se derivaron dos categorías temáticas: 1) Factores que influencian la formación del apego y la parentalidad, y 2) Apego y relaciones parentales. Resultados: Se señalaron las lagunas existentes en lo que se refiere a la producción científica específicamente al tema enumerado, identificando la diversidad de estudios que engloban los sistemas de apego y temas transversales, como apego y desarrollo infantil, apego y psicopatología, apego y maternidad, entre otros. Además, no se encontraron estudios nacionales sobre la temática, así como investigaciones transculturales al respecto. En relación al delineamiento de los estudios encontrados, todos se caracterizan por el enfoque cuantitativo y estudios longitudinales del tipo prospectivo follow-up. Las técnicas de recolección de datos que más sobresalieron fueron la Entrevista de Apego Adulto (AAI), seguida de la Situación Extraña en investigaciones con muestras infantiles. Conclusión: Se destaca que la Teoría del Apego necesita estar abierta para la revisión y la consideración de las dimensiones relacionadas a la cultura. Esto implica ajustarla a diferentes contextos culturales, históricos y sociales. Se sugiere, por lo tanto, el incremento de nuevos estudios que contemplen la formación del apego, los cuales vengan a diseminar intervenciones parentales positivas para el ciclo de vida personal y familiar de los sujetos.

No cenário atual, pode-se observar uma mudança nos papéis desempenhados pelos pais e mães na interação com seus filhos. A paternidade, por exemplo, passou a ser alvo das pesquisas científicas recentemente, tendo em vista a maior participação do pai na vida dos filhos. Dessa forma, esta pesquisa teve como objetivo identificar os fatores que interferem no envolvimento paterno de pais (homens) de crianças entre quatro a seis anos. Trata-se de um estudo exploratório descritivo, de natureza qualitativa, cujos dados foram coletados através de uma entrevista semiestruturada, a qual foi analisada pela técnica da análise de conteúdo categorial temática, utilizando-se o software Atlas.ti. Da análise das entrevistas emergiram quatro categorias: Vivência da paternidade; Responsabilidade; Interação pai-filho e Fatores que interferem no envolvimento paterno. Neste artigo serão apresentados os resultados da última categoria, por estarem diretamente relacionados com o objetivo deste estudo. Os resultados apontam que o modelo de paternidade que os participantes tiveram de seus próprios pais, além das relações que estabelecem com a mãe da criança, as características pessoais dos pais e dos filhos e, ainda, a rede de apoio que possuem, constituíram-se em aspectos que repercutiram no envolvimento paterno.DOI http://dx.doi.org/10.21452/2594-43632018v27n61a04

Este trabalho tem como objetivo demonstrar o desenvolvimento de novas atividades para aprimorar relacao entre “ensino-aprendizagem”, tendo como base a monitoria voluntaria na disciplina de Geoquimica Orgânica e Geoquimica do Petroleo, enfatizando a importância da aplicacao deste metodo para auxiliar e maximizar o ensino dos alunos, colaborando na formacao e qualificacao dos alunos da Engenharia de Petroleo da UFPel.A monitoria tem como principal proposta, combater os indices de reprovacao e desistencia da disciplina, assim como, do curso, desenvovendo metodos que auxiliam no progresso do aluno. Logo, estes metodos incluem exercicios teoricos semanais (conhecido informalmente como quiz ); exercicios periodicos mais complexos, os testes; analise critica de artigos cientificos; seminarios; indicacoes de bibliografias para leitura e auxilio nas duvidas durante o semestre.A adocao dos metodos citados no presente projeto apontaram um avanco no aprendizado, ja que os metodos resultaram no aumento do interesse dos alunos, e consequentemente uma diminuicao de desistencias e reprovacoes, cumprindo o seu objetivo principal. A partir dos dados de evasao e das respostas do formulario feito pelos proprios alunos, comprova-se um significativo avanco na qualidade de ensino nas disciplinas de Geoquimica Orgânica e Geoquimica do Petroleo.

Supplementary data to this article can be found online at https:// doi.org/10.1016/j.meegid.2018.10.025. The human-restricted bacterium Haemophilus influenzae is responsible for respiratory infections in both children and adults. While colonization begins in the upper airways, it can spread throughout the respiratory tract potentially leading to invasive infections. Although the spread of H. influenzae serotype b (Hib) has been prevented by vaccination, the emergence of infections by other serotypes as well as by non-typeable isolates (NTHi) have been observed, prompting the need for novel prevention strategies. Here, we aimed to study the population structure of H. influenzae and to get some insights into its pan-genome. We studied 305H. influenzae strains, enrolling 217 publicly available genomes, as well as 88 newly sequenced H. influenzae invasive strains isolated in Portugal, spanning a 24-year period. NTHi isolates presented a core-SNP-based genetic diversity about 10-fold higher than the one observed for Hib. The analysis of key factors involved in pathogenesis, such as lipooligosaccharides, hemagglutinating pili and High Molecular Weight-adhesins, suggests that NTHi shape its virulence repertoire, either by acquisition and loss of genes or by SNP-based diversification, likely towards host immune evasion and persistence. Discreet NTHi subpopulations structures are proposed based on core-genome supported with 17 candidate genetic markers identified in the accessory genome. Additionally, this study provides two bioinformatics tools for in silico rapid identification of H. influenzae serotypes and NTHi clades previously proposed, obviating laboratory-based demanding procedures. The present study constitutes an important genomic framework that could lay way for future studies on the genetic determinants underlying invasiveness and disease and population structure of H. influenzae. This work was supported by GenomePT (ref. POCI-01-0145-FEDER022184) from Fundação para a Ciência e Tecnologia, Portugal. info:eu-repo/semantics/publishedVersion

Resumo: O objetivo deste estudo foi identificar as aprendizagens de participantes de grupos de pais do Programa ACT, intervenção psicoeducativa que visa auxiliar no desenvolvimento de práticas educativas parentais positivas, propiciando às crianças ambientes mais seguros, saudáveis, estáveis, sem violência e maus-tratos. Os dados foram organizados de acordo com a análise categorial temática. Os resultados indicaram que a participação no ACT possibilitou aprendizagens sobre práticas educativas parentais, o reconhecimento de emoções dos adultos e das crianças, a compreensão acerca dos estilos parentais, a importância do envolvimento dos pais para o desenvolvimento da criança, além de aprendizagens sobre desenvolvimento infantil e aspectos relacionados a exposição às mídias eletrônicas na primeira infância. Este estudo apresentou como contribuição às pesquisas do Programa ACT uma análise qualitativa de aspectos específicos concernentes às aprendizagens realizadas nas sessões e resultados de grupos que incluíram a participação de pais (homens) no contexto brasileiro, diferenciando-se de estudos anteriores apenas com mães. Resumen: El objetivo de este estudio fue identificar los aprendizajes de los participantes de los grupos de padres del Programa ACT, intervención psicoeducativa que tiene como objetivo ayudar en el desarrollo de prácticas parentales positivas, proporcionando a los niños entornos más seguros, saludables y estables, sin violencia y abuso. Los datos se organizaron según el análisis categórico temático. Los resultados indicaron que la participación en el Programa ACT permitió aprender sobre prácticas educativas, el reconocimiento de las emociones de adultos y niños, la comprensión de estilos parentales, la importancia de la participación de los padres para el desarrollo infantil, así como el aprendizaje sobre el desarrollo infantil y los aspectos relacionados a la exposición a los medios electrónicos em la primera infancia. Este estudio presentó como contribución a la investigación del Programa ACT un análisis cualitativo de aspectos específicos del aprendizaje realizado en las sesiones y resultados de grupos que incluyeron la participación de padres (hombres) en el contexto brasileño, diferenciándose de estudios previos solo con madres. Abstract: The aim of this study was to identify the new learning of participants of an ACT Program parent group. This psychoeducational intervention aims to assist in the development of positive parenting practices, providing children safer, healthier, more stable environments, without violence or abuse. Data were organized according to thematic categorical analysis. The results indicated that participation in the ACT Program enabled learning about parenting practices, the recognition of emotions of the adults and children, understanding about parenting styles, the importance of parental involvement for child development, and learning about child development and aspects related to exposure to electronic media in early childhood. As a contribution to the ACT Program research, this study presented a qualitative analysis of specific aspects concerning the content learned in the sessions and results of groups that included the participation of fathers in the Brazilian context, differing from previous studies with only mothers.

Abstract: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

DNA methylation is a type of epigenetic modification that affects gene expression regulation and is associated with several human diseases. Microarray and short read sequencing technologies are often used to study 5’-methylcytosine (5’-mC) modification of CpG dinucleotides in the human genome. Although both technologies produce trustable results, the evaluation of the methylation status of CpG sites suffers from the potential side effects of DNA modification by bisulfite and the ambiguity of mapping short reads in repetitive and highly homologous genomic regions, respectively. Nanopore sequencing is an attractive alternative for the study of 5’-mC since the long reads produced by this technology allow to resolve those genomic regions more easily. Moreover, it allows direct sequencing of native DNA molecules using a fast library preparation procedure. In this work we show that 10X coverage depth nanopore sequencing, using DNA from a human cell line, produces 5’-mC methylation frequencies consistent with those obtained by methylation microarray and digital restriction enzyme analysis of methylation. In particular, the correlation of methylation values ranged from 0.73 to 0.90 using an average genome sequencing coverage depth 0.89) between sequencing runs and an almost uniform variation in methylation frequencies of CpGs across the entire value range. Furthermore, nanopore sequencing was able to correctly display methylation frequency patterns according to genomic annotations, including a majority of unmethylated and methylated sites in the CpG islands and inter-CpG island regions, respectively. These results demonstrate that low coverage depth nanopore sequencing is a fast, reliable and unbiased approach to the study of 5’-mC in the human genome.

Background and objectivesTo understand how organisms evolve, it is fundamental to study how mutations emerge and establish. Here, we estimated the rate of mutation accumulation of SARS-CoV-2 in vitro and investigated the repeatability of its evolution when facing a new cell type but no immune or drug pressures.MethodologyWe performed experimental evolution with two strains of SARS-CoV-2, one carrying the originally described spike protein (CoV-2-D) and another carrying the D614G mutation that has spread worldwide (CoV-2-G). After 15 passages in Vero cells and whole genome sequencing, we characterized the spectrum and rate of the emerging mutations and looked for evidences of selection across the genomes of both strains.ResultsFrom the mutations accumulated, and excluding the genes with signals of selection, we estimate a spontaneous mutation rate of 1.25×10-6 nt-1 per infection cycle for both lineages of SARS-CoV-2. We further show that mutation accumulation is heterogeneous along the genome, with the spike gene accumulating mutations at rate five-fold higher than the genomic average. We also observe the emergence of mutators in the CoV-2-G background, likely linked to mutations in the RNA-dependent RNA polymerase and/or in the error-correcting exonuclease protein.Conclusions and implicationsThese results provide valuable information on how spontaneous mutations emerge in SARS-CoV-2 and on how selection can shape its genome towards adaptation to new environments.Lay summaryMutation is the ultimate source of variation. We estimated how the SARS-COV-2 virus—cause of the COVID-19 pandemic—mutates. Upon infecting cells, its genome can change at a rate of 0.04 per replication. We also find that this rate can change and that its spike protein can adapt, even within few replications.

Traumatic brain injury (TBI) is a serious public health problem, affecting 69 million people worldwide annually. Mild TBI (mTBI) comprises the majority of the cases and remains the most neglected TBI severity. Its intricate pathophysiology involves complex cellular and molecular processes that remain uncomprehended. Although the renin-angiotensin system (RAS) has its well-known roles in blood pressure regulation and fluid balance, accumulating evidence demonstrates its active expression and signaling in the central nervous system. Over the past years, pre-clinical studies have been supporting the role of RAS in mTBI. However, particularly for human TBI, evidence is still missing. Herein, we investigated peripheral levels of angiotensin II (Ang II) and angiotensin-converting enzyme (ACE), components of RAS classical axis, as well as angiotensin-(1-7) [Ang-(1-7)] and ACE2, components of RAS counter-regulatory axis, in 28 mTBI patients and 24 healthy controls. In the first 24 h, mTBI patients displayed lower ACE (p = 0.0004) and ACE2 (p = 0.0047) concentrations and an increase in Ang II (p = 0.0234) and Ang-(1-7) (p = 0.0225) levels compared to controls. Interestingly, at 30 days follow-up, mTBI patients increased the levels of ACE (p = 0.0415) and ACE2 (p = 0.0416) along with a decrease in Ang II (p = 0.0039) and Ang-(1-7) (p = 0.0015) concentrations compared with their measures at 24 h after TBI. Also, our receiver operating curve (ROC) analysis demonstrated that ACE concentration was a good predictor of mTBI diagnosis (AUC = 0.798, p 0.0001). The current study provides the first clinical evidence of RAS molecule's involvement in mTBI and their possible role as discriminating biomarkers.

BackgroundDissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare institutions affects both patients and health-care workers (HCW), as well as the institutional capacity to provide essential health services.MethodsWe conducted an investigation of a cluster of SARS-CoV-2 positive cases detected in a “non-COVID-19” hospital ward during Summer 2020. The magnitude of the nosocomial outbreak was disclosed by massive testing, challenging the retrospective reconstruction of the introduction and transmission events. An in-depth contact tracing investigation was carried out to identify the contacts network during the 15-day period before the screening. In parallel, positive SARS-CoV-2 RNA samples were subjected to virus genome sequencing.ResultsOf the 245 tested individuals, 48 (21 patients and 27 HCWs) tested positive for SARS-CoV-2. HCWs were mostly asymptomatic, but the mortality among the vulnerable patient group reached 57.1% (12/21). Phylogenetic reconstruction revealed that all cases were part of the same transmission chain, thus confirming a single origin behind this nosocomial outbreak. By combining vast epidemiological and genomic data, including analysis of emerging minor variants, we unveiled a scenario of silent SARS-CoV-2 dissemination within the hospital ward, mostly driven by the close contact within the HCWs group and between HCWs and patients. This investigation triggered enhanced prevention and control measures, leading to a more timely detection and containment of novel nosocomial outbreaks.ConclusionsThe present study shows the benefit of combining genomic and epidemiological data for the investigation of complex nosocomial outbreaks, and provides valuable data to minimize the risk of transmission of COVID-19 in healthcare facilities.Short summarySARS-CoV-2 nosocomial outbreaks are of utmost public health concern. Here, we performed an in-depth investigation of a high-fatality rate nosocomial outbreak by combining vast genomic and epidemiological data, providing valuable information to understand cryptic transmission of SARS-CoV-2 within healthcare institutions.