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This study sought to examine the correlation between left ventricular (LV) myocardial feature tracking (FT) and deep learning-based strain (DLS) analysis in the diagnostic (CMRd) and follow-up (CMRf) cardiac magnetic resonance imaging of patients with acute myocarditis. The retrospective study included 17 patients with acute myocarditis and 20 healthy controls. The CMRd took place within 14 days of symptom onset, while the CMRf took place at least 2 months after the event. The global-circumferential FT (FTc) and global-circumferential DLS (DLSc) were analyzed. The continuous variables were compared using paired t-tests or the Wilcoxon test, whereas Pearson's test or Spearman's test was used to evaluate the correlation between the continuous variables. The time between the CMRd and CMRf was 5 months [3-11]. The LV ejection fraction (LVEF) was 55 ± 6 and 59 ± 4%, p = 0.008, respectively, and 94.1% of the patients showed late gadolinium enhancement (LGE) and myocardial edema on the CMRd. Significantly lower FTc (-16.1 ± 2.2% vs. -18.9 ± 1.9%, p = 0.001) and DLSc (-38.1 ± 5.2% vs. -41.3 ± 4.5%, p = 0.015) were observed with respect to the controls. Significant increases in the FTc (-16.1 ± 2.2 vs. -17.5 ± 1.9%, p = 0.016) and DLSc (-38.1 ± 5.2 vs. -39.8 ± 3.9%, p = 0.049) were found between the CMRd and CMRf, which were unrelated to the LGE. The LVEF correlated well with the FTc (r = 0.840) and DLSc (r = 0.760). Both techniques had excellent reproducibility, with high intra- (FTc = 0.980, DLSc = 1.000) and inter-observer (FTc = 0.970, DLSc = 0.980) correlation. There was correlation between the LV DLSc/FTc and LVEF in the patients with acute myocarditis according to the CMRd and CMRf.
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BACKGROUND: Viral lower respiratory tract infections (LRTI) are the leading cause of hospitalization in children. In Catalonia (Spain), information is scarce about the burden of viral LRTIs in paediatric hospitalizations. The aim of this study is to describe epidemiological, clinical, virological and economic features of paediatric hospitalizations due to viral LRTI. METHODS: From October 2012 to December 2020, children aged <16 years admitted to a tertiary paediatric hospital in Catalonia (Spain) with confirmed viral LRTI were included in the study. Virus seasonality, prevalence, age and sex distribution, clinical characteristics, hospital costs and bed occupancy rates were determined. RESULTS: A total of 3,325 children were included (57.17% male, 9.44% with comorbidities) accounting for 4056 hospitalizations (32.47% ≤ 12 months): 53.87% with wheezing/asthma, 37.85% with bronchiolitis and 8.28% with pneumonia. The most common virus was respiratory syncytial virus (RSV) (52.59%). Influenza A was associated with pneumonia (odds ratio [OR] 7.75) and caused longer hospitalizations (7 ± 31.58 days), while RSV was associated with bronchiolitis (OR 6.62) and was the most frequent reason for admission to the paediatric intensive care unit (PICU) (11.23%) and for respiratory support (78.76%). Male sex, age ≤12 months, chronic conditions and bronchiolitis significantly increased the odds of PICU admission. From October to May, viral LRTIs accounted for 12.36% of overall hospital bed days. The total hospitalization cost during the study period was 16,603,415. CONCLUSIONS: Viral LRTIs are an important cause of morbidity, hospitalization and PICU admission in children. The clinical burden is associated with significant bed occupancy and health-care costs, especially during seasonal periods.
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Bronquiolite , COVID-19 , Pneumonia , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Criança , Humanos , Masculino , Lactente , Feminino , Criança Hospitalizada , Espanha/epidemiologia , Hospitalização , Infecções Respiratórias/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologiaRESUMO
4-dimensional-flow cardiac magnetic resonance in patients with aortic dissection in chronic/post repair phase as a complementary diagnostic tool for anatomic-functional evaluation. Quali-quantitative analysis of 3 patients with this pathology clearly showing the true/false lumen, quantitative flow in false lumen, and helping in discerning lumen origin from different arterial vessels. (Level of Difficulty: Advanced.).
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[This corrects the article DOI: 10.1007/s42843-022-00055-8.].
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Almost two years into the pandemic, the scientific and healthcare communities continue to learn a great deal regarding COVID-19, the disease produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Broad variability during acute COVID-19 infection is seen, ranging from asymptomatic presentation to death. The vast majority of individuals who develop COVID-19 return to their pre-COVID-19 baseline within several weeks. However, a portion of patients will develop a post-COVID-19 syndrome of persistent cognitive, somatic, and behavioral symptoms. This syndrome, designated as post-acute sequelae of SARS-CoV-2 infection, is more commonly known as long COVID. The objectives of this paper are to inform psychologists regarding our current understanding of the underlying pathophysiology of COVID-19, review criteria for range of severity during acute illness, present clinical manifestations of long haul phenomena, and discuss the emerging literature base of evidence-based treatment and management approaches.
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The Burnout Assessment Tool (BAT) has been gaining increased attention as a sound and innovative instrument in its conceptualization of burnout. BAT has been adapted for several countries, revealing promising validity evidence. This paper aims to present the psychometric properties of the Brazilian and Portuguese versions of the BAT in both the 23-item and 12-item versions. BAT's validity evidence based on the internal structure (dimensionality, reliability, and measurement invariance) and validity evidence based on the relations to other variables are the focus of research. A cross-sectional study was conducted with two non-probabilistic convenience samples from two countries (N = 3103) one from Brazil (nBrazil = 2217) and one from Portugal (nPortugal = 886). BAT's original structure was confirmed, and it achieved measurement invariance across countries. Using both classic test theory and item response theory as frameworks, the BAT presented good validity evidence based on the internal structure. Furthermore, the BAT showed good convergent evidence (i.e., work engagement, co-worker support, role clarity, work overload, and negative change). In conclusion, the psychometric properties of the BAT make this freely available instrument a promising way to measure and compare burnout levels of Portuguese and Brazilian workers.
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Esgotamento Psicológico , Brasil/epidemiologia , Estudos Transversais , Humanos , Portugal , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
This study aimed to adapt and show evidence of validity for the Ecuadorian version of the Burnout Assessment Tool (BAT) considering only its "core" dimensions. The adaptation process included its translation and back translation. For content validation, expert reviews and focus groups were carried out. A confirmatory factor analysis was used to identify the psychometric properties and dimensionality of the scale. The reliability of the scale was assessed through the alpha, omega and composite reliability indices. To carry out the study, the questionnaire was applied to a sample of workers with a high level of education in Ecuador. In total, 2237 respondents were considered in the analysis. The results showed that the hierarchical model for BAT-23 and its short version, the BAT-12 scale, is the most adequate structure for analysis of the construct in the Ecuadorian context. The reliability of the general factor of burnout and its dimensions, evaluated by composite reliability, omega and Cronbach's alpha, showed satisfactory indices. The findings obtained provide support for the reliability and validity of the Burnout Assessment Tool for the Ecuadorian context.
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Esgotamento Psicológico , Traduções , Equador , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Objectives: The recent health crisis has led to a tightening of visitor policies during medical consultations. This work studies the relationship between the companion's health literacy (functional, interactive, and critical) and the companion's co-creation of value (co-production and value in use). Methods: Six hypotheses are tested by means of a sample of companions of chronically ill patients over the age of 65, using structural equation modeling. Results: Functional literacy does not predict the co-creation of value through either of its dimensions (co-production and value in use). Interactive literacy has a positive influence on co-production and a negative influence on value in use. Critical literacy only positively influences value in use. Discussion: Merely understanding the health information is not sufficient for the companion to be recognized as a collaborator or "ally" of the doctor. It is necessary to encourage the companion's communication and critical evaluation skills.
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Letramento em Saúde , Médicos , Doença Crônica , Comunicação , Amigos , HumanosRESUMO
Modern genomic data sets often involve multiple data-layers (e.g., DNA-sequence, gene expression), each of which itself can be high-dimensional. The biological processes underlying these data-layers can lead to intricate multivariate association patterns. We propose and evaluate two methods to determine the proportion of variance of an output data set that can be explained by an input data set when both data panels are high dimensional. Our approach uses random-effects models to estimate the proportion of variance of vectors in the linear span of the output set that can be explained by regression on the input set. We consider a method based on an orthogonal basis (Eigen-ANOVA) and one that uses random vectors (Monte Carlo ANOVA, MC-ANOVA) in the linear span of the output set. Using simulations, we show that the MC-ANOVA method gave nearly unbiased estimates. Estimates produced by Eigen-ANOVA were also nearly unbiased, except when the shared variance was very high (e.g., >0.9). We demonstrate the potential insight that can be obtained from the use of MC-ANOVA and Eigen-ANOVA by applying these two methods to the study of multi-locus linkage disequilibrium in chicken (Gallus gallus) genomes and to the assessment of inter-dependencies between gene expression, methylation, and copy-number-variants in data from breast cancer tumors from humans (Homo sapiens). Our analyses reveal that in chicken breeding populations ~50,000 evenly-spaced SNPs are enough to fully capture the span of whole-genome-sequencing genomes. In the study of multi-omic breast cancer data, we found that the span of copy-number-variants can be fully explained using either methylation or gene expression data and that roughly 74% of the variance in gene expression can be predicted from methylation data.
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Genômica/métodos , Análise de Variância , Animais , Neoplasias da Mama/genética , Galinhas/genética , Variações do Número de Cópias de DNA , Metilação de DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Desequilíbrio de Ligação , Método de Monte Carlo , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do GenomaRESUMO
Baseados na perspectiva da complexidade do comportamento humano, avanços científicos têm sido obtidos por pesquisadores da Psicologia Positiva ao identificar fatores de saúde e de proteção das pessoas em concomitância com os de risco de dano ou agravo á saúde. Esse artigo teórico visa demonstrar o impacto desses achados para a Psicologia Organizacional e do Trabalho, com base em três conceitos centrais. São apresentados no artigo os modelos teóricos que fundamentam as evidências e os principais achados nos estudos sobre bem-estar, engajamento e redesenho do trabalho. A principal contribuição é que as pesquisas estão sendo impulsionadas com modelos integrativos sobre esses fenômenos e suas associações com variáveis de felicidade, proatividade e realização profissional, dentre outras. Somada ao conhecimento dos estudos tradicionais, a Psicologia Positiva possibilita a visão sistêmica sobre trabalho e organizações, tratando a saúde e o bem-estar como premissas do contexto laboral e o desempenho saudável como desfecho positivo das atividades profissionais. (AU)
Based on the perspective of the complexity of human behavior, scientific advances are being obtained in Positive Psychology by identifying protective factors concurrently with those that cause risk or harm to health. This theoretical article aims to demonstrate the influence of these findings on organizational and work psychology, based on evidence produced in three central constructs. We present the theoretical models that support the evidence and main findings of studies on well-being, engagement and job crafting. The main contribution is that the studies are being driven with integrative models on these phenomena and their associations with happiness, proactivity and professional achievement variables, among others. Added to the knowledge of the traditional studies, Positive Psychology enables a systemic view of work and organizations, treating health and well-being as premises of the work context and healthy performance as a positive outcome of professional activities. (AU)
Con base en la perspectiva de la complejidad del comportamiento humano, avances científicos están siendo obtenidos por los investigadores de la psicología positiva al identificar factores de salud y de protección de las personas en concomitancia con los riesgos de daño o agravio de la salud. Este artículo teórico tiene como objetivo demostrar su impacto en la psicología organizacional y laboral, basada en tres constructos centrales. Se presentan modelos teóricos que respaldan las evidencias y los principales hallazgos en los estudios sobre bienestar, rendimiento y job crafting. La principal contribución es que las integraciones están siendo impulsadas con modelos integradores sobre estos fenómenos y sus asociaciones con las variables de felicidad, proactividad, logro profesional, entre otros. Además del conocimiento de los estudios tradicionales, la psicología positiva permite una visión sistémica del trabajo y las organizaciones, tratando la salud y el bienestar como premisas del contexto laboral y el rendimiento saludable como un resultado positivo de las actividades profesionales. (AU)
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Humanos , Psicologia , Seguridade Social/psicologia , Saúde Ocupacional , Engajamento no Trabalho , Satisfação no EmpregoRESUMO
Esse estudo visa investigar a relação entre Burnout e satisfação de vida em trabalhadores brasileiros pelo modelo teórico Job Demands-Resources (JDR), da Psicologia Positiva. Foram testadas as associações entre Burnout e demandas e recursos de trabalho, satisfação de vida e sintomas depressivos, em 986 participantes das cinco regiões brasileiras, entre 18 e 89 anos (M = 39, DP = 11,1), sendo 87,2% de mulheres. Os resultados demonstram que Burnout prediz sintomas depressivos e é consequente de altas demandas e baixos recursos laborais. O papel de mediação parcial da satisfação de vida se destaca quando associado aos recursos de trabalho, o que diminui a probabilidade de ocorrência do Burnout e sintomas depressivos associados. Conclui-se que recursos de trabalho e satisfação de vida são importantes fatores psicossociais de proteção ao Burnout, que influenciam indireta e negativamente sintomas depressivos. Contribuições desses achados para o trabalho e as organizações são discutidas no texto. (AU)
This study aims to investigate the relationship between burnout and life satisfaction in Brazilian workers through the Job Demands-Resources (JDR) theoretical model of Positive Psychology. The associations between burnout and job demands, job resources, life satisfaction and depressive symptoms were tested in 986 participants, 87.2% women, from the five Brazilian regions, aged between 18 and 89 years (M = 39, SD = 11.1). The results show that high job demands and low job resources are indirectly linked with depressive symptoms via burnout and low life satisfaction. The partial mediation role of life satisfaction stands out when associated with job resources, which reduces the likelihood of burnout and its association with depressive symptoms. It was concluded that job resources and life satisfaction are important psychosocial protective factors for burnout, which impacts indirectly and negatively on depressive symptoms. Contributions of these findings for work and organizations are discussed in the text. (AU)
Este estudio tiene como objetivo investigar la relación entre el burnout y la satisfacción con la vida en los trabajadores brasileños a través del modelo teórico Job Demand Resources (JDR), de la psicología positiva. Las asociaciones entre burnout y demandas y recursos laborales, satisfacción con la vida y síntomas depresivos fueron probadas en 986 participantes de las cinco regiones brasileñas, los participantes poseían edades entre 18 y 89 años (M = 39, DS = 11.1), siendo el 87.2% mujeres. Los resultados demuestran que el burnout predice síntomas depresivos motivados por las altas demandas y bajos recursos laborales. El papel de la mediación parcial de la satisfacción con la vida se destaca cuando se asocia con recursos laborales, lo que reduce la probabilidad de burnout y los síntomas depresivos asociados. Se concluye que los recursos laborales y la satisfacción con la vida son factores psicosociales importantes de protección contra el burnout, que influyen indirectamente y negativamente en los síntomas depresivos. Las contribuciones de estos hallazgos para el trabajo y las organizaciones se discuten en el artículo. (AU)
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Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Psicologia , Seguridade Social/psicologia , Saúde Mental , Depressão/psicologia , Esgotamento Psicológico/psicologia , Satisfação no Emprego , Estudos de Avaliação como AssuntoRESUMO
Gratidão é um estado mental positivo de agradecimento por experiências de vida, adversas ou de risco, vinculadas à memória das lembranças afetivas que aumentam o bem-estar subjetivo. Foi desenvolvida uma escala brasileira com o objetivo de mensurar o construto da gratidão, definida para esta pesquisa. A escala original com 13 itens, construída e revisada com base nos padrões internacionais, foi preenchida por 762 participantes (625 mulheres, 82%; 137 homens), entre 18 e 90 anos, M = 41, DP = 13. A análise fatorial exploratória extraiu sete itens com estrutura interna unidimensional, resultando na Escala Brasileira de Gratidão (B-GRAT). A análise fatorial confirmatória, pela matriz de correlações policóricas demonstrou índice adequado para o modelo testado e consistência interna de a = 0,84. Foi testada a correlação de Pearson com a Escala de Esperança Disposicional. Os resultados indicam evidência da adequação psicométrica da B-GRAT na avaliação da gratidão no Brasil. (AU)
Gratitude is a positive mental state of gratefulness for adverse or risky life experiences related to affective memories that improve the subjective well-being. A new scale was developed aiming to produce an instrument for the assessment of gratitude. An original pool of 13 items, constructed and reviewed using accurate standards, was responded to by 762 participants (242 females, 72.5%; 88 males), aged 18-90 years, M = 41, SD = 13. An Exploratory Factor Analysis concluded with the selection of 7 items that presented an internal unidimensional structure, resulting in the Brazilian scale of Gratitude (B-GRAT). Confirmatory Factor Analysis using the polychoric correlations matrix showed an adequate fit of the model and an internal consistency de α = 0.84. The concurrent validity with the Hope Index Scale was checked by means of Pearson's correlation. The results indicate evidence that the B-GRAT is psychometrically adequate to assess gratitude in Brazil. (AU)
La gratitud es un estado mental positivo de agradecimiento por las experiencias de la vida, adversas o arriesgadas, relacionadas con la memoria afectiva que aumentan el bienestar subjetivo. Se desarrolló una escala brasileña con el propósito de medir el constructo de gratitud, definido para esta investigación. La escala original con 13 ítems, construida y revisada según los estándares internacionales, fue completada por 762 participantes (625 mujeres, 82%, 137 hombres), entre 18 y 90 años, M = 41, DS = 13. El análisis factorial exploratorio reveló 7 ítems con una estructura interna unidimensional, lo que resultó en la Escala de Gratitud Brasileña (B-GRAT). El análisis factorial confirmatorio, por la matriz de correlaciones policóricas, presentó un índice adecuado para el modelo probado y una consistencia interna de α= 0.84. La correlación de Pearson fue probada con la escala de esperanza disposicional. Los resultados indican evidencia de la adecuación psicométrica de B-GRAT en la evaluación de la gratitud en Brasil. (AU)
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Psicologia , Seguridade Social/psicologia , Reconhecimento Psicológico , Esperança , Otimismo , Reprodutibilidade dos Testes , Análise FatorialRESUMO
BACKGROUND/OBJECTIVES: Little is currently known about how exercise may influence dietary patterns and/or food preferences. The present study aimed to examine the effect of a 15-week exercise training program on overall dietary patterns among young adults. SUBJECTS/METHODS: This study consisted of 2680 young adults drawn from the Training Intervention and Genetics of Exercise Response (TIGER) study. Subjects underwent 15 weeks of aerobic exercise training, and exercise duration, intensity, and dose were recorded for each session using computerized heart rate monitors. In total, 4355 dietary observations with 102 food items were collected using a self-administered food frequency questionnaire before and after exercise training (n = 2476 at baseline; n = 1859 at 15 weeks). Dietary patterns were identified using a Bayesian sparse latent factor model. Changes in dietary pattern preferences were evaluated based on the pre/post-training differences in dietary pattern scores, accounting for the effects of gender, race/ethnicity, and BMI. RESULTS: Within each of the seven dietary patterns identified, most dietary pattern scores were decreased following exercise training, consistent with increased voluntary regulation of food intake. A longer duration of exercise was associated with decreased preferences for the western (ß: -0.0793; 95% credible interval: -0.1568, -0.0017) and snacking (ß: -0.1280; 95% credible interval: -0.1877, -0.0637) patterns, while a higher intensity of exercise was linked to an increased preference for the prudent pattern (ß: 0.0623; 95% credible interval: 0.0159, 0.1111). Consequently, a higher dose of exercise was related to a decreased preference for the snacking pattern (ß: -0.0023; 95% credible interval: -0.0042, -0.0004) and an increased preference for the prudent pattern (ß: 0.0029; 95% credible interval: 0.0009, 0.0048). CONCLUSIONS: The 15-week exercise training appeared to motivate young adults to pursue healthier dietary preferences and to regulate their food intake.
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Dieta/estatística & dados numéricos , Exercício Físico , Promoção da Saúde/métodos , Adulto , Índice de Massa Corporal , Registros de Dieta , Feminino , Preferências Alimentares , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários , Adulto JovemRESUMO
This paper presents a systematic review of Brazilian and international studies on the assessment of psychosocial factors, published between 2009 and 2015, with emphasis on the analysis of assessment instruments. One of the main interests of this review was to identify, in the published articles, the use of principles of Positive Psychology in the analysis of factors of prevention, promotion and health protection of workers. A total of 5,724 articles were found. Articles that were repeated or not written in Portuguese, English or Spanish were excluded. Thus, after analysis, 410 articles remained. Of these, 69 articles that dealt directly with the evaluation of psychosocial factors at work were selected. Most studies address the pathogenesis of psychosocial factors, but there is increasing number of studies that combine the analyses of pathogenic factors with motivational factors in health promotion and in the study of preserved positive aspects. We found that although the findings indicate an incipient movement concerning some protective factors (social support, creativity, engagement, etc.), there are still few studies in the Positive Psychology approach. We suggest that further studies test integrative theoretical models or stressors and motivational factors to deepen the understanding of the protective factors and positive aspects associated with psychosocial factors at work.
Este artigo realiza uma revisão sistemática nos estudos brasileiros e internacionais para a avaliação de fatores psicossociais, entre 2009 e 2015, com ênfase na análise de instrumentos de avaliação. Um dos interesses principais nessa revisão foi identificar a utilização dos princípios da Psicologia Positiva na análise dos fatores de prevenção, promoção e proteção à saúde dos trabalhadores nos artigos investigados. Foram encontrados 5.724 artigos. Foram excluídos trabalhos repetidos e não escritos em português, inglês ou espanhol. Restaram 410 artigos. Destes foram selecionados 69 que tratavam diretamente sobre avaliação dos fatores psicossociais do trabalho. A maioria dos estudos lida com a patogênese dos fatores psicossociais, mas há uma produção crescente combinando análises de fatores patogênicos com fatores motivacionais na promoção da saúde e no estudo de aspectos positivos preservados. Constatou-se que embora os achados indiquem um movimento incipiente de considerar alguns fatores protetivos (suporte social, criatividade, engajamento, etc.), ainda há poucos estudos no enfoque da Psicologia Positiva. Sugere-se que estudos futuros testem modelos teóricos integrativos ou fatores estressores e motivacionais para aprofundar o entendimento dos fatores de proteção e aspectos positivos associados a fatores psicossociais no trabalho.
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Masculino , Feminino , Psicologia , Saúde Ocupacional , Impacto PsicossocialRESUMO
BACKGROUND: Current sequence-based approaches to identify enzyme functional shifts, such as enzyme promiscuity, have proven to be highly dependent on a priori functional knowledge, hampering our ability to reconstruct evolutionary history behind these mechanisms. Hidden Markov Model (HMM) profiles, broadly used to classify enzyme families, can be useful to distinguish between closely related enzyme families with different specificities. The (ßα)8-isomerase HisA/PriA enzyme family, involved in L-histidine (HisA, mono-substrate) biosynthesis in most bacteria and plants, but also in L-tryptophan (HisA/TrpF or PriA, dual-substrate) biosynthesis in most Actinobacteria, has been used as model system to explore evolutionary hypotheses and therefore has a considerable amount of evolutionary, functional and structural knowledge available. We searched for functional evolutionary intermediates between the HisA and PriA enzyme families in order to understand the functional divergence between these families. RESULTS: We constructed a HMM profile that correctly classifies sequences of unknown function into the HisA and PriA enzyme sub-families. Using this HMM profile, we mined a large metagenome to identify plausible evolutionary intermediate sequences between HisA and PriA. These sequences were used to perform phylogenetic reconstructions and to identify functionally conserved amino acids. Biochemical characterization of one selected enzyme (CAM1) with a mutation within the functionally essential N-terminus phosphate-binding site, namely, an alanine instead of a glycine in HisA or a serine in PriA, showed that this evolutionary intermediate has dual-substrate specificity. Moreover, site-directed mutagenesis of this alanine residue, either backwards into a glycine or forward into a serine, revealed the robustness of this enzyme. None of these mutations, presumably upon functionally essential amino acids, significantly abolished its enzyme activities. A truncated version of this enzyme (CAM2) predicted to adopt a (ßα)6-fold, and thus entirely lacking a C-terminus phosphate-binding site, was identified and shown to have HisA activity. CONCLUSION: As expected, reconstruction of the evolution of PriA from HisA with HMM profiles suggest that functional shifts involve mutations in evolutionarily intermediate enzymes of otherwise functionally essential residues or motifs. These results are in agreement with a link between promiscuous enzymes and intragenic epistasis. HMM provides a convenient approach for gaining insights into these evolutionary processes.
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Bactérias/enzimologia , Bactérias/genética , Evolução Molecular , Isomerases/química , Isomerases/genética , Metagenoma , Bactérias/classificação , Sítios de Ligação , Histidina/biossíntese , Cadeias de Markov , Mutagênese Sítio-Dirigida , Filogenia , Especificidade por Substrato , Triptofano/biossínteseRESUMO
Type 2 Diabetes (T2D) is a chronic disease arising from the development of insulin absence or resistance within the body, and a complex interplay of environmental and genetic factors. The incidence of T2D has increased throughout the last few decades, together with the occurrence of the obesity epidemic. The consideration of variants identified by Genome Wide Association Studies (GWAS) into risk assessment models for T2D could aid in the identification of at-risk patients who could benefit from preventive medicine. In this study, we build several risk assessment models, evaluated with two different classification approaches (Logistic Regression and Neural Networks), to measure the effect of including genetic information in the prediction of T2D. We used data from to the Original and the Offspring cohorts of the Framingham Heart Study, which provides phenotypic and genetic information for 5245 subjects (4306 controls and 939 cases). Models were built by using several covariates: gender, exposure time, cohort, body mass index (BMI), and 65 SNPs associated to T2D. We fitted Logistic Regressions and Bayesian Regularized Neural Networks and then assessed their predictive ability by using a ten-fold cross validation. We found that the inclusion of genetic information into the risk assessment models increased the predictive ability by 2%, when compared to the baseline model. Furthermore, the models that included BMI at the onset of diabetes as a possible effector, gave an improvement of 6% in the area under the curve derived from the ROC analysis. The highest AUC achieved (0.75) belonged to the model that included BMI, and a genetic score based on the 65 established T2D-associated SNPs. Finally, the inclusion of SNPs and BMI raised predictive ability in all models as expected; however, results from the AUC in Neural Networks and Logistic Regression did not differ significantly in their prediction accuracy.
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Lifestyle and genetic factors play a large role in the development of Type 2 Diabetes (T2D). Despite the important role of genetic factors, genetic information is not incorporated into the clinical assessment of T2D risk. We assessed and compared Whole Genome Regression methods to predict the T2D status of 5,245 subjects from the Framingham Heart Study. For evaluating each method we constructed the following set of regression models: A clinical baseline model (CBM) which included non-genetic covariates only. CBM was extended by adding the first two marker-derived principal components and 65 SNPs identified by a recent GWAS consortium for T2D (M-65SNPs). Subsequently, it was further extended by adding 249,798 genome-wide SNPs from a high-density array. The Bayesian models used to incorporate genome-wide marker information as predictors were: Bayes A, Bayes Cπ, Bayesian LASSO (BL), and the Genomic Best Linear Unbiased Prediction (G-BLUP). Results included estimates of the genetic variance and heritability, genetic scores for T2D, and predictive ability evaluated in a 10-fold cross-validation. The predictive AUC estimates for CBM and M-65SNPs were: 0.668 and 0.684, respectively. We found evidence of contribution of genetic effects in T2D, as reflected in the genomic heritability estimates (0.492±0.066). The highest predictive AUC among the genome-wide marker Bayesian models was 0.681 for the Bayesian LASSO. Overall, the improvement in predictive ability was moderate and did not differ greatly among models that included genetic information. Approximately 58% of the total number of genetic variants was found to contribute to the overall genetic variation, indicating a complex genetic architecture for T2D. Our results suggest that the Bayes Cπ and the G-BLUP models with a large set of genome-wide markers could be used for predicting risk to T2D, as an alternative to using high-density arrays when selected markers from large consortiums for a given complex trait or disease are unavailable.
Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Genótipo , Polimorfismo de Nucleotídeo Único , Adulto , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Modelos Genéticos , Fenótipo , Locos de Características QuantitativasRESUMO
BACKGROUND/AIMS: To quantify the extent to which the increase in obesity observed across recent generations of the American population is associated with the individual or combined effects of assortative mating (AM) for body mass index (BMI) and differential realized fertility by BMI. METHODS: A Monte Carlo framework is formed and informed using data collected from the National Longitudinal Survey of Youth (NLSY). The model has 2 portions: one that generates childbirth events on an annual basis and another that produces a BMI for each child. Once the model is informed using the data, a reference distribution of offspring BMIs is simulated. We quantify the effects of our factors of interest by removing them from the model and comparing the resulting offspring BMI distributions with that of the baseline scenario. RESULTS: An association between maternal BMI and number of offspring is evidenced in the NLSY data as well as the presence of AM. These 2 factors combined are associated with an increased mean BMI (+0.067, 95% CI: 0.056; 0.078), an increased BMI variance (+0.578, 95% CI: 0.418; 0.736) and an increased prevalence of obesity (RR 1.032, 95% CI: 1.023; 1.041) and BMIs >40 (RR 1.083, 95% CI: 1.053; 1.118) among offspring. CONCLUSION: Our investigation suggests that both differential realized fertility and AM by BMI appear to play a role in the increasing prevalence of obesity in America.
Assuntos
Índice de Massa Corporal , Fertilidade/genética , Padrões de Herança/genética , Obesidade/genética , Comportamento Reprodutivo , Humanos , Modelos Genéticos , Método de Monte Carlo , ProbabilidadeRESUMO
West Nile virus, genus Flavivirus, is transmitted between birds and occasionally other animals by ornithophilic mosquitoes. This virus also infects humans causing asymptomatic infections in about 85% of cases and <1% of clinical cases progress to severe neuroinvasive disease. The virus also presents a threat since most infections remain unapparent. However, the virus contained in blood and organs from asymptomatically infected donors can be transmitted to recipients of these infectious tissues. This paper reviews the presently available methods to achieve the laboratory diagnosis of West Nile virus infections in humans, discussing the most prominent advantages and disadvantages of each in light of the results obtained during four different External Quality Assessment studies carried out by the European Network for 'Imported' Viral Diseases (ENIVD).