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

Occurrence of 15 haplotypes of linepithema micans (Hymenoptera: Formicidae) in southern Brazil.

The ant genus Linepithema is widely known, thanks to the pest species Linepithema humile (Mayr), which is easily mistaken for Linepithema micans (Forel) due to their morphological similarity. Like L. humile , L. micans is associated to the main grapevine pest in Brazil, Eurhizococcus brasiliensis (Wille), also known as ground pearl. Therefore, the present study uses mtDNA fragments to expand the knowledge of haplotype diversity and distri- bution of L. micans in the state of Rio Grande do Sul Brazil), to understand the genetic differences of the popu- lations identified in this study. We identified 15 haplotypes of L. micans spread across different localities. Twelve of these haplotypes were new for the species. The high haplotype diversity uncovered in Rio Grande do Sul (Brazil) for this species was predictable, as L. micans is in its native environment. Additional studies that take gene flow into account may reveal interesting aspects of diversity in these populations. Keywords: mitotype, ground pearl, Rio Grande do Su

Cardiovascular risk biomarkers and metabolically unhealthy status in prepubertal children: Comparison of definitions

Background and aims: The early onset of cardio-metabolic abnormalities, known as metabolically unhealthy (MU) status, is highly associated with obesity and cardiovascular disease (CVD), as well as with increased morbidity and mortality later in life. Given the lack of a consensus MU classification for prepubertal children, we aimed to compare available MU definitions in terms of their association with CVD risk biomarkers. Methods and results: A total of 930 prepubertal children (622 with overweight/obesity, 462 males) aged 5–10.9 years were recruited, anthropometric measures were taken and biomarkers were analyzed. Children were classified using eight MU definitions based on different cut-offs for blood pressure, triacylglycerides, high-density lipoprotein cholesterol, glucose and homeostasis model assessment for insulin resistance (HOMA-IR). MU prevalence in children with overweight/obesity ranged between 30% and 60% across definitions. Plasma concentrations of resistin, leptin, myeloperoxidase (MPO) and total plasminogen activator inhibitor 1 (tPAI-1) were higher, and those of adiponectin were lower, in MU compared to MH children with overweight/obesity. Linear regression analyses confirmed the contribution of MPO and tPAI-1 concentrations to MU status, with most significant results derived from definitions that use age and sex-specific criteria and that account for HOMA-IR. Conclusion: Plasma concentrations of MPO and tPAI-1 are increased in prepubertal MU children irrespective of having normal-weight or overweight/obesity. Inclusion of age and sex-specific cut-offs for cardio-metabolic components as well as insulin resistance criteria increases the quality of MU definitions as seen by their stronger association with CVD biomarkers concentrations

Height-based equations as screening tools for high blood pressure in pediatric practice, the GENOBOX study

Due to the absence of easily applicable cut-off points to determine high blood pressure or hypertension in children, as in the adult population, blood pressure is rarely measured in the pediatrician''s clinical routine. This has led to an underdiagnosis of high blood pressure or hypertension in children. For this reason, the present study evaluate the utility of five equations for the screening of high blood pressure in children: blood pressure to height ratio, modified blood pressure to height ratio, new modified blood pressure to height ratio, new simple formula and height-based equations. The authors evaluated 1599 children between 5 and 18 years. The performance of the five equations was analyzed using the receiver-operating characteristics curves for identifying blood pressure above P90th according to the American Academy of Pediatrics Clinical Practice Guideline 2017. All equations showed an area under the curve above 0.882. The new modified blood pressure to height ratio revealed a high sensitivity whereas the height-based equations showed the best performance, with a positive predictive value above 88.2%. Finally, all equations showed higher positive predictive values in children with overweight or obesity. The height-based equation obtained the highest PPV values above 71.1% in children with normal weight and above 90.2% in children with overweight or obesity. In conclusions, the authors recommend the use of the height-based equations equation because it showed the best positive predictive values to identify children with elevated blood pressure, independently of their sex, pubertal and weight status. © 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC

The vitamin D decrease in children with obesity is associated with the development of insulin resistance during puberty: The PUBMEP study

Obesity and cardiometabolic risk have been associated with vitamin D levels even in children. The objective of the present study was to evaluate the association between insulin resistance (IR), cardiometabolic risk factors, and vitamin D in children from prepubertal to pubertal stages. A total of 76 children from the PUBMEP study, aged 4–12 years at baseline, were included. Children were evaluated in prepubertal and pubertal stages. Anthropometric measurements and selected cardiometabolic risk biomarkers, such as plasma glucose, blood lipids, insulin, adiponectin, leptin, and blood pressure, and serum 25-hydroxyvitamin D (25(OH)D) were determined. Children were categorized by obesity degree and IR status combined before and after puberty. Paired t-test and multivariate linear regression analyses were conducted. During puberty, the increase in triacylglycerols, insulin, and HOMA-IR and the decrease in QUICKI were significantly associated with the reduction in 25(OH)D (B = -0.274, p = 0.032; B = -0.219, p = 0.019; B = -0.250, p = 0.013; B = 1.574, p = 0.013, respectively) after adjustment by BMI-z, sex, and pubertal stage. Otherwise, prepubertal non-IR children with overweight/obesity that became IR during puberty showed a significant decrease in 25(OH)D and HDL-c, and an increase in waist circumference and triacylglycerol concentrations (p < 0.05 for all) over time. These results suggest that changes in IR seem to be associated with an effect on 25(OH)D levels during puberty, especially in children with overweight. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Evaluation of Sedentary Behavior and Physical Activity Levels Using Different Accelerometry Protocols in Children from the GENOBOX Study

Background Physical activity (PA) has acquired a significant relevance due to the health benefits associated with its practice. Accelerometers are an effective tool to assess PA; however, the diversity of cut-off points used to define different PA intensities through accelerometry could interfere in the interpretation of the findings among studies. Objectives The present study aimed to examine the sedentary behavior (SB) and physical activity (PA) levels in children using six selected accelerometry protocols based on diverse cut-off points. Methods Clinical examination, anthropometric measurements, and PA evaluation by accelerometry were assessed in 543 selected children (10 +/- 2.4 years old) from the Spanish GENOBOX study. The ActiLife data scoring program was used to determine daily min spent in SB, and light, moderate, vigorous and moderate-vigorous PA using six validated accelerometry protocols differing in their cut-off points. Results Very different estimations for SB and PA intensity levels were found in children, independently of the non-wear-time algorithm selected, and considering puberty stages, age and body mass index. The time spent in daily SB varied from 471 to 663.7 min, PA ranged from 141 to 301.6 min, and the moderate-vigorous PA was reported between 20.7 and 180.2 min. Conclusion The choice of a particular accelerometry protocol considering these factors is important to evaluate SB or PA intensities to suit the characteristics of the sample researched. It seems necessary to establish future lines of research that include different analytical approaches to measure SB and PA by accelerometry based on standardized and validated methodology

Dietary patterns and their association with body composition and cardiometabolic markers in children and adolescents: Genobox cohort

Diet is a key factor for obesity development; however, limited data are available on dietary cluster analysis in children with obesity. We aimed to assess the associations between dietary patterns and obesity and several cardiometabolic markers. Anthropometry, bioelectrical impedance, blood pressure and plasma biomarkers of oxidative stress, inflammation and endothelial damage were determined in 674 Caucasian children, aged 5–16, with normal or excess weight. Using a food frequency questionnaire and cluster analysis, two consistent dietary patterns were shown, labeled as health conscious (HC) and sweet and processed (SP). The HC pattern included a greater proportion of participants with overweight/obesity than the SP cluster (80.1% vs. 63.8%). However, children with obesity within the HC cluster, showed less abdominal fat, through waist to hip (0.93 vs. 0.94) and waist to height (0.61 vs. 0.63) indexes (p < 0.01). Univariate general models showed several additional differences in cardiometabolic risk biomarkers in the global and stratified analyses, with a healthier profile being observed mainly in the HC cluster. However, multivariate models questioned these findings and pointed out the need for further studies in this field. Anyhow, our findings support the benefits of a healthy diet and highlight the importance of dietary patterns in the cardiometabolic risk assessment of children with overweight/obesity, beyond weight control

Evaluation of the Predictive Ability, Environmental Regulation and Pharmacogenetics Utility of a BMI-Predisposing Genetic Risk Score during Childhood and Puberty

The authors would like to thank the Spanish children and parents who participated in the study.Polygenetic risk scores (pGRSs) consisting of adult body mass index (BMI) genetic variants have been widely associated with obesity in children populations. The implication of such obesity pGRSs in the development of cardio-metabolic alterations during childhood as well as their utility for the clinical prediction of pubertal obesity outcomes has been barely investigated otherwise. In the present study, we evaluated the utility of an adult BMI predisposing pGRS for the prediction and pharmacological management of obesity in Spanish children, further investigating its implication in the appearance of cardio-metabolic alterations. For that purpose, we counted on genetics data from three well-characterized children populations (composed of 574, 96 and 124 individuals), following both cross-sectional and longitudinal designs, expanding childhood and puberty. As a result, we demonstrated that the pGRS is strongly associated with childhood BMI Z-Score (B = 1.56, SE = 0.27 and p-value = 1.90 × 10−8 ), and that could be used as a good predictor of obesity longitudinal trajectories during puberty. On the other hand, we showed that the pGRS is not associated with cardio-metabolic comorbidities in children and that certain environmental factors interact with the genetic predisposition to the disease. Finally, according to the results derived from a weight-reduction metformin intervention in children with obesity, we discarded the utility of the pGRS as a pharmacogenetics marker of metformin response.Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI1102042 PI1102059 PI1601301 PI1600871Spanish Ministry of Health, Social and Equality, General Department for Pharmacy and Health Products EC10-243 EC10-056 EC10-281 EC10-227Regional Government of Andalusia ("Plan Andaluz de investigacion, desarrollo e innovacion (2018)") P18-RT-2248Mapfre Foundation ("Research grants by Ignacio H. de Larramendi 2017")Instituto de Salud Carlos III IFI17/0004

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

Prepubertal Children With Metabolically Healthy Obesity or Overweight Are More Active Than Their Metabolically Unhealthy Peers Irrespective of Weight Status: GENOBOX Study

Background and Aim: The association of a metabolically healthy status with the practice of physical activity (PA) remains unclear. Sedentarism and low PA have been linked to increased cardiometabolic risk. The aim of this study was to evaluate the PA levels in metabolically healthy (MH) or unhealthy (MU) prepubertal children with or without overweight/obesity. Methods: A total 275 children (144 boys) with 9 ± 2 years old were selected for the GENOBOX study. PA times and intensities were evaluated by accelerometry, and anthropometry, blood pressure, and blood biochemical markers were analyzed. Children were considered to have normal weight or obesity, and further classified as MH or MU upon fulfillment of the considered metabolic criteria. Results: Classification resulted in 119 MH children (21% with overweight/obesity, referred to as MHO) and 156 MU children (47% with overweight/obesity, referred to as MUO). Regarding metabolic profile, MHO showed lower blood pressure levels, both systolic and diastolic and biochemical markers levels, such as glucose, Homeostatic Model Assessment of Insulin Resistance, triglycerides and higher HDL-c levels than MUO (P < 0.001). In addition, MHO children spent more time in PA of moderate intensity compared with MUO children. In relation to vigorous PA, MH normal weight (MHN) children showed higher levels than MUO children. Considering sex, boys spent more time engaged in moderate, vigorous, and moderate–vigorous (MV) PA than girls, and the number of boys in the MH group was also higher. Conclusion: Prepubertal MHO children are less sedentary, more active, and have better metabolic profiles than their MUO peers. However, all children, especially girls, should increase their PA engagement, both in terms of time and intensity because PA appears to be beneficial for metabolic health status itself. Copyright © 2022 Llorente-Cantarero, Leis, Rupérez, Anguita-Ruiz, Vázquez-Cobela, Flores-Rojas, González-Gil, Aguilera, Moreno, Gil-Campos and Bueno