Metallochaperones Are Needed for Mycobacterium tuberculosis and Escherichia coli Nicotinamidase-Pyrazinamidase Activity.

Mycobacterium tuberculosis nicotinamidase-pyrazinamidase (PZAse) is a metalloenzyme that catalyzes conversion of nicotinamide-pyrazinamide to nicotinic acid-pyrazinoic acid. This study investigated whether a metallochaperone is required for optimal PZAse activity. M. tuberculosis and Escherichia coli PZAses (PZAse-MT and PZAse-EC, respectively) were inactivated by metal depletion (giving PZAse-MT-Apo and PZAse-EC-Apo). Reactivation with the E. coli metallochaperone ZnuA or Rv2059 (the M. tuberculosis analog) was measured. This was repeated following proteolytic and thermal treatment of ZnuA and Rv2059. The CDC1551 M. tuberculosis reference strain had the Rv2059 coding gene knocked out, and PZA susceptibility and the pyrazinoic acid (POA) efflux rate were measured. ZnuA (200 μM) achieved 65% PZAse-EC-Apo reactivation. Rv2059 (1 μM) and ZnuA (1 μM) achieved 69% and 34.3% PZAse-MT-Apo reactivation, respectively. Proteolytic treatment of ZnuA and Rv2059 and application of three (but not one) thermal shocks to ZnuA significantly reduced the capacity to reactivate PZAse-MT-Apo. An M. tuberculosis Rv2059 knockout strain was Wayne positive and susceptible to PZA and did not have a significantly different POA efflux rate than the reference strain, although a trend toward a lower efflux rate was observed after knockout. The metallochaperone Rv2059 restored the activity of metal-depleted PZAse in vitro Although Rv2059 is important in vitro, it seems to have a smaller effect on PZA susceptibility in vivo. It may be important to mechanisms of action and resistance to pyrazinamide in M. tuberculosis Further studies are needed for confirmation.IMPORTANCE Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis and remains one of the major causes of disease and death worldwide. Pyrazinamide is a key drug used in the treatment of tuberculosis, yet its mechanism of action is not fully understood, and testing strains of M. tuberculosis for pyrazinamide resistance is not easy with the tools that are presently available. The significance of the present research is that a metallochaperone-like protein may be crucial to pyrazinamide's mechanisms of action and of resistance. This may support the development of improved tools to detect pyrazinamide resistance, which would have significant implications for the clinical management of patients with tuberculosis: drug regimens that are appropriately tailored to the resistance profile of a patient's individual strain lead to better clinical outcomes, reduced onward transmission of infection, and reduction of the development of resistant strains that are more challenging and expensive to treat

Educação, currículo escolar e protagonismo juvenil: os desafios da educação na contemporaneidade

Resumo: Este artigo se insere no debate sobre educação e política, abordando a relação entre educação, currículo escolar e violência simbólica na perspectiva de adolescentes entre 12 e 17 anos que cumprem medidas socioeducativas no CREAS (Centro de Referência Especializada da Assistência Social) de Vitória, Brasil. Através de nossas análises, percebemos que a educação apresenta desafios, contradições e tensões decorrentes principalmente da organização da sociedade contemporânea, que acaba por reforçar a exclusão desses alunos. Além disso, apontamos a discrepância entre a regulamentação dessas medidas e o cotidiano escolar bem como a falta de protagonismo dos sujeitos envolvidos no cumprimento dessas medidas como alguns obstáculos do processo de inclusão desses adolescentes. Palavras-chave: Educação; Currículo Escolar; Protagonismo Juvenil e Violência.   Resumen: Este artículo se inserta en el debate sobre educación y política, con un enfoque en la relación entre educación, plan de estudios y violencia simbólica en la perspectiva del adolescente entre 12 y 17 años que cumple una “medida socioeducativa” en el CREAS (Centro de Referência Especializado de la Asistencia Social) de Vitória, Brasil. Mediante nuestros análisis percibimos que la educación presenta desafíos, contradicciones y tensiones derivadas principalmente de la organización de la sociedad contemporánea, que refuerza la exclusión. Además, señalamos la discrepancia entre la regulación de la medida, y el cotidiano escolar, así como la falta de protagonismo de los sujetos involucrados en el cumplimiento de las medidas como algunos obstáculos del proceso de inclusión de estos adolescentes. Palabras clave: Educación; Plan de Estudios; Protagonismo Juvenil y Violencia.   Abstract: The theme of this article is inserted in the debate on education and politics in a way that relates education, curriculum and symbolic violence in the perspective of adolescents at the age range of 12 to 17 years who are under socio-educational measures in the CREAS (Specialized Center of Reference in Social Work) of Vitoria, Brazil. Throughout some analysis we realized that education presents challenges, contradictions and tensions mainly due to the organization of contemporary society, which reinforces exclusion. In addition, we identified the discrepancy between the regulation of these measures and the school routine, and the lack of leadership of the individuals complying with the measures as some of the obstacles these adolescents face in the social inclusion process. Keywords: Education; School Curriculum; Youth Participation and Violence

Reliability and Validation of the Child Eating Behavior Questionnaire in 3- to 6-Year-Old Spanish Children

Introduction: Eating behavior is often established during the first years of life. Therefore, it is important to make a research on it to understand the relationships that children have with food and how this can contribute to prevent the development of childhood obesity. An appropriate assessment of eating behavior can be achieved using the “Child Eating Behavior Questionnaire” (CEBQ). This questionnaire has been validated in several populations and languages, but it has never been translated, adapted, and validated for Spanish children. Aim: To evaluate the reliability and internal consistency of the CEBQ questionnaire, culturally adapted and translated into Spanish (Spain), in Spanish families with children aged 3 to 6 years, as well as its association with children’s body mass index (BMI) to test its construct validity. Materials and Methods: Children between 3 and 6 years old were recruited from the ongoing MELI-POP randomized controlled clinical trial, as well as from public schools located in middle class neighborhoods of Zaragoza, Spain, to complete the sample. Sociodemographic characteristics and anthropometric measures were obtained according to standardized methods. The 35-item CEBQ questionnaire was completed twice with a time difference of 3 weeks between each response. Statistical analyses included the evaluation of internal consistency and reliability of the questionnaire, a confirmatory factor analysis, and the association between the different CEBQ scales and the children’s BMI. Results: A total of 197 children completed variables; 97 of them were boys (49.2%) and 100 girls (50.8%). Mean age of the total sample was 4.7 ± 0.9 years. There was a high test-re-test reliability of the questionnaire with values close to 1, with an average of 0.66 and a good internal consistency (Cronbach alpha with values above 0.7), so that a high reliability is established between the items in each scale. A gradual positive association was found between the score of different “pro-intake” scales of the CEBQ: “Food Responsiveness, ” “Emotional Overeating, ” and “Enjoyment of food” and the children’s BMI; at the opposite, negative associations were observed between BMI and the score of anti-intake scales “Satiety Responsiveness, ” “Slowness in Eating, ” and “Emotional Undereating.” Conclusion: The Spanish version of the CEBQ is a useful tool to assess the eating behavior of Spanish children because the high reliability and internal validity. There is a significant association between eating behavior and BMI in Spanish children. Copyright © 2022 Jimeno-Martínez, Maneschy, Moreno, Bueno-Lozano, De Miguel-Etayo, Flores-Rojas, Jurado-Castro, de Lamas, Vázquez-Cobela, Martinez-Lacruz, Portoles, Martínez, Navas-Carretero, Schröder, Fitó, Babio, Salas-Salvadó, Leis, Gil-Campos and Rupérez

O LÚDICO NO PROCESSO PEDAGÓGICO DA EDUCAÇÃO INFANTIL: IMPORTANTE, PORÉM AUSENTE

This study observed and analyzed the presence of playful teaching practice on the educational action of teachers in the kindergarten school both from the public and private sectors in the city of São José do Rio Preto. By means of a bibliographical and empirical research, schools from four different parts of the city were evaluated and systematically observed. Later, a questionnaire was applied to the teachers. The main objective was to verify whether or not there were situations in which playful activities would be part of the teacher’s daily agenda, either as a planned activity or even used randomly, as well as the understanding of the teachers concerning this matter in the infantile education.Este estudio analisó la presencia del juguete en el hacer pedagógico de las maestras en guarderías de la red pública de la ciudad de São José do Rio Preto. Por medio de encuestas bibliográficas y empíricas, fueran abordadas escuelas distribuidas en los cuatro sectores de la ciudad en los cuales se realizó una observación sistematizada, y después la aplicación de una encuesta con los maestros. El objectivo primero fue verificar si en el cotidiano de las escuelas tenía o no situaciones de utilización de actividades lúdicas, planeamento de las actividades o empleo obligatorio, como también la comprensión de las mismas acerca de los juguetes infantiles.Este estudo observou e analisou a presença do lúdico no fazer educacional das professoras das escolas infantis das redes pública e particular da cidade de São José do Rio Preto. Por meio de pesquisas bibliográfica e empírica, foram abordadas escolas distribuídas nos quatro setores da cidade, nas quais se realizou, primeiramente, uma observação sistematizada e posteriormente a aplicação de um questionário junto às professoras. O principal objetivo foi verificar se no cotidiano escolar das unidades de ensino infantil envolvidas na pesquisa havia ou não situações de utilização de atividades lúdicas, planejamento das atividades ou seu uso aleatório, assim como a compreensão das professoras acerca do brincar na educação infantil. Os dados coletados foram tratados de modo comparativo entre os dois modelos de escolas compreendidas nos setores público e privado, o que possibilitou traçar um percurso do lúdico na educação infantil e no fazer pedagógico das professoras que, na época, atuavam nos distintos segmentos com a respectiva faixa etária

Study of breast cancer incidence in patients of lymphangioleiomyomatosis

The online version of this article (doi:10.1007/s10549-016-3737-8) contains supplementary material, which is available to authorized user

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types