Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia

Low folate intake as well as alterations in folate metabolism as a result of polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with an increased incidence of neural tube defects, vascular disease, and some cancers. Polymorphic variants of MTHFR lead to enhanced thymidine pools and better quality DNA synthesis that could afford some protection from the development of leukemias, particularly those with translocations. We now report associations of MTHFR polymorphisms in three subgroups of pediatric leukemias: infant lymphoblastic or myeloblastic leukemias with MLL rearrangements and childhood lymphoblastic leukemias with either TEL-AML1 fusions or hyperdiploid karyotypes. Pediatric leukemia patients (n = 253 total) and healthy newborn controls (n = 200) were genotyped for MTHFR polymorphisms at nucleotides 677 (C→T) and 1,298 (A→C). A significant association for carriers of C677T was demonstrated for leukemias with MLL translocations (MLL+, n = 37) when compared with controls [adjusted odd ratios (OR) = 0.36 with a 95% confidence interval (CI) of 0.15–0.85; P = 0.017]. This protective effect was not evident for A1298C alleles (OR = 1.14). In contrast, associations for A1298C homozygotes (CC; OR = 0.26 with a 95% CI of 0.07–0.81) and C677T homozygotes (TT; OR = 0.49 with a 95% CI of 0.20–1.17) were observed for hyperdiploid leukemias (n = 138). No significant associations were evident for either polymorphism with TEL-AML1+ leukemias (n = 78). These differences in allelic associations may point to discrete attributes of the two alleles in their ability to alter folate and one-carbon metabolite pools and impact after DNA synthesis and methylation pathways, but should be viewed cautiously pending larger follow-up studies. The data provide evidence that molecularly defined subgroups of pediatric leukemias have different etiologies and also suggest a role of folate in the development of childhood leukemia.

Developmental Activities That Lead to Dropout and Investment in Sport

Background: Studies suggest that expert performance in sport is the result of long-term engagement in a highly specialized form of training termed deliberate practice. The relationship between accumulated deliberate practice and performance predicts that those who begin deliberate practice at a young age accumulate more practice hours over time and would, therefore, have a significant performance advantage. However, qualitative studies have shown that a large amount of sport-specific practice at a young age may lead to negative consequences, such as dropout, and is not necessarily the only path to expert performance in sport. Studies have yet to investigate the activity context, such as the amount of early sport participation, deliberate play and deliberate practice within which dropout occurs. Purpose: To determine whether the nature and amount of childhood-organized sport, deliberate play and deliberate practice participation influence athletes' subsequent decisions to drop out or invest in organized sport. It was hypothesized that young athletes who drop out will have sampled fewer sports, spent less time in deliberate play activities and spent more time in deliberate practice activities during childhood sport involvement. Participants: The parents of eight current, high-level, male, minor ice hockey players formed an active group. The parents of four high-level, male, minor ice hockey players who had recently withdrawn from competitive hockey formed a dropout group. Data collection: Parents completed a structured retrospective survey designed to assess their sons' involvement in organized sport, deliberate play and deliberate practice activities from ages 6 to 13. Data analysis: A complete data-set was available for ages 6 through 13, resulting in a longitudinal data-set spanning eight years. This eight-year range was divided into three levels of development corresponding to the players' progress through the youth ice hockey system. Level one encompassed ages 6–9, level two included ages 10–11 and level three covered ages 12–13. Descriptive statistics were used to report the ages at which the active and dropout players first engaged in select hockey activities. ANOVA with repeated measures across the three levels of development was used to compare the number of sports the active and dropout players were involved in outside of hockey, the number of hours spent in these sports, and involvement in various hockey-related activities. Findings: Results indicated that both the active and dropout players enjoyed a diverse and playful introduction to sport. Furthermore, the active and dropout players invested similar amounts of time in organized hockey games, organized hockey practices, specialized hockey training activities (e.g. hockey camps) and hockey play. However, analysis revealed that the dropout players began off-ice training at a younger age and invested significantly more hours/year in off-ice training at ages 12–13, indicating that engaging in off-ice training activities at a younger age may have negative implications for long-term ice hockey participation. Conclusion: These results are consistent with previous research that has found that early diversification does not hinder sport-specific skill development and it may, in fact, be preferable to early specialization. The active and dropout players differed in one important aspect of deliberate practice: off-ice training activities. The dropout players began off-ice training at a younger age, and participated in more off-ice training at ages 12 and 13 than their active counterparts. This indicates a form of early specialization and supports the postulate that early involvement in practice activities that are not enjoyable may ultimately undermine the intrinsic motivation to continue in sport. Youth sport programs should not focus on developing athletic fitness through intense and routine training, but rather on sport-specific practice, games and play activities that foster fun and enjoyment.

ISSP Position Stand: To Sample or to Specialize? Seven Postulates About Youth Sport Activities that Lead to Continued Participation and Elite Performance

A comprehensive approach to sport expertise should consider the entire situation that is comprised of the person, the task, the environment, and the complex interplay of these components (Hackfort, 1986). Accordingly, the Developmental Model of Sport Participation (Côté, Baker, & Abernethy, 2007; Côté & Fraser-Thomas, 2007) provides a comprehensive framework for sport expertise that outlines different pathways of involvement in sport. In pathways one and two, early sampling serves as the foundation for both elite and recreational sport participation. Early sampling is based on two main elements of childhood sport participation: 1) involvement in various sports and 2) participation in deliberate play. In contrast, pathway three shows the course to elite performance through early specialization in one sport. Early specialization implies a focused involvement on one sport and a large number of deliberate practice activities with the goal of improving sport skills and performance during childhood. This paper proposes seven postulates regarding the role that sampling and deliberate play, as opposed to specialization and deliberate practice, can have during childhood in promoting continued participation and elite performance in sport.

Expression of SHOX in human fetal and childhood growth plate

Abnormalities in the growth plate may lead to short stature and skeletal deformity including Leri Weil syndrome, which has been shown to result from deletions or mutations in the SHOX gene, a homeobox gene located at the pseudoautosomal region of the X and Y chromosome. We studied the expression of SHOX protein, by immunohistochemistry, in human fetal and childhood growth plates and mRNA by in situ hybridization in childhood normal and Leri Weil growth plate. SHOX protein was found in reserve, proliferative, and hypertrophic zones of fetal growth plate from 12 wk to term and childhood control and Leri Weil growth plates. The pattern of immunostaining in the proliferative zone of childhood growth plate was patchy, with more intense uniform immunostaining in the hypertrophic zone. In situ hybridization studies of childhood growth plate demonstrated SHOX mRNA expression throughout the growth plate. No difference in the pattern of SHOX protein or mRNA expression was seen between the control and Leri Weil growth plate. These findings suggest that SHOX plays a role in chondrocyte function in the growth plate.

Childhood abuse is associated with structural impairment in the ventrolateral prefrontal cortex and aggressiveness in patients with borderline personality disorder

Volume reduction and functional impairment in areas of the prefrontal cortex (PFC) have been found in borderline personality disorder (BPD), particularly in patients with a history of childhood abuse. These abnormalities may contribute to the expression of emotion dysregulation and aggressiveness. In this study we investigated whether the volume of the PFC is reduced in BPD patients and whether a history of childhood abuse would be associated with greater PFC structural changes. Structural MRI data were obtained from 18 BPD patients and 19 healthy individuals matched for age, sex, handedness, and education and were analyzed using voxel based morphometry. The Child Abuse Scale was used to elicit a past history of abuse; aggression was evaluated using the Buss-Durkee Hostility Inventory (BDHI). The volume of the right ventrolateral PFC (VLPFC) was significantly reduced in BPD subjects with a history of childhood abuse compared to those without this risk factor. Additionally, right VLPFC gray matter volume significantly correlated with the BDHI total score and with BDHI irritability and negativism subscale scores in patients with a history of childhood abuse. Our results suggest that a history of childhood abuse may lead to increased aggression mediated by an impairment of the right VLPFC. © 2013 Elsevier Ireland Ltd.

ISSP Position Stand: To Sample or to Specialize? Seven Postulates About Youth Sport Activities that Lead to Continued Participation and Elite Performance

A comprehensive approach to sport expertise should consider the entire situation that is comprised of the person, the task, the environment, and the complex interplay of these components (Hackfort, 1986). Accordingly, the Developmental Model of Sport Participation (Côté, Baker, & Abernethy, 2007; Côté & Fraser-Thomas, 2007) provides a comprehensive framework for sport expertise that outlines different pathways of involvement in sport. In pathways one and two, early sampling serves as the foundation for both elite and recreational sport participation. Early sampling is based on two main elements of childhood sport participation: 1) involvement in various sports and 2) participation in deliberate play. In contrast, pathway three shows the course to elite performance through early specialization in one sport. Early specialization implies a focused involvement on one sport and a large number of deliberate practice activities with the goal of improving sport skills and performance during childhood. This paper proposes seven postulates regarding the role that sampling and deliberate play, as opposed to specialization and deliberate practice, can have during childhood in promoting continued participation and elite performance in sport.

Clinical Signs and Symptoms and Laboratory Findings of Methadone Poisoning in Children

Background: Poisoning accounts for about 7% of all accidents in children under 5 years and is implicated in over 5% of all childhood deaths in developing countries. Objectives: Due to the potential risks of methadone poisoning in children and increased cases of methadone poisoning among Iranian children, this study was conducted to investigate the clinical signs and symptoms and laboratory findings of methadone toxicity in children. Patients and Methods: The present retrospective, descriptive, cross-sectional study describes the clinical symptoms and signs and laboratory findings of methadone poisoning in children under 12 years old in Shahid Beheshti Hospital, Kashan, during the years 2009 to 2013. Results: Of 58 patients, 33 (56.9%) were male and 25 (43.1%) female (P = 0.294). The mean age of patients was 5.2 ± 1.0 years. All the cases of poisoning happened with methadone syrup, due to unsafe keeping of methadone in mineral water bottles and containers of other drugs. Signs and symptoms included drowsiness (91.4 %), miosis (75.9%), vomiting (69.0%), ineffective breathing (any kind of breathing problem except apnea) (62.1%), apnea (53.4%), cyanosis (43.1%), seizure (8.6%), ataxia (6.9%) and delirium (3.4%). Conclusions: Keeping methadone in appropriate containers and warning methadone consumers about the dangerous side effects of its consumption and the symptoms of methadone poisoning in children may minimize the occurrence of this form of poisoning and its complications in children.

Peer interaction in mixed age groups: a study in the computer area of an early childhood education center in Portugal

The study was developed as a teacher-research project during initial teacher education – Masters Degree of Early Childhood and Primary Education, in Portugal. It analysed the interactions between children of 3 to 6 years old, during the use of the computer as a free choice activity, confronting situations between peers of the same age and situations between peers of different ages. The focus of the analysis was the collaborative interactions. This was a qualitative study. Children could choose the computer, amongst other interest areas, and work for around an hour in pairs. In the computer, children used mainly educational games. During four weeks, the interactions between the pairs were audio recorded. Field notes and informal interviews to the children were also used to collect data. Eleven children were involved in the study with ages ranging from 3 to 6 years old. Baseline data on children’s basic computer proficiency was collected using the Individualized Computer Proficiency Checklist (ICPC) by Hyun. The recorded interactions were analysed using the types of talk offered by Scrimshaw and Perkins and Wegerif and Scrimshaw: cumulative talk, exploratory talk, disputational talk, and tutorial talk. This framework was already used in a study in an early childhood education context in Portugal by Amante. The results reveal differences in computer use and characterize the observed interactions. Seven different pairs of children's interactions were analysed. More than a third of the interactions were cumulative talk, followed by exploratory talk, tutorial talk and disputational talk. Comparing same and mixed age pairs, we observed that cumulative talk is the more present interaction, but in same age pairs this is followed by exploratory talk whereas in the mixed age pairs it is tutorial talk that has the second largest percentage. The pairs formed by the children were very asymmetrical in terms of age and computer proficiency. This lead to the more tutorial interactions, where one children showed the other or directed him/her on how to play. The results show that collaboration is present during the use of a computer area in early childhood education. The free choice of the children means the adults can only suggest pairing suited to specific interactions between the children. Another way to support children in more exploratory talk interactions could be by discussing the way the older children can help the younger ones beyond directing or correcting their work.

Migraine Equivalents In Childhood.

Migraine equivalents are a group of periodic and paroxysmal neurologic diseases. Because headache is not a prominent symptom, the diagnosis might be challenging. The objective of the study was to evaluate the frequency and outcome of migraine equivalents. This was a retrospective study. We included benign paroxysmal torticollis of infancy, benign paroxysmal vertigo of infancy, abdominal migraine, cyclic vomiting, aura without migraine, and confusional migraine. We evaluated the frequency of events, treatment, and outcome. Out of 674 children with headache, 38 (5.6%) presented with migraine equivalents. Twenty-one were boys and the mean age was 6.1 years. Fifteen had abdominal migraine, 12 benign paroxysmal vertigo, 5 confusional migraine, 3 aura without migraine, 2 paroxysmal torticollis, and 1 cyclic vomiting. Prophylactic treatment was introduced in 23 patients; 4 lost follow-up and 19 had significant improvement. We conclude that the correct diagnosis of migraine equivalents enables an effective treatment with an excellent outcome.

Phenotypic Polymorphism Of Chrysomya Albiceps (wiedemann) (diptera: Calliphoridae) May Lead To Species Misidentification.

Species identification is an essential step in the progress and completion of work in several areas of biological knowledge, but it is not a simple process. Due to the close phylogenetic relationship of certain species, morphological characters are not always sufficiently distinguishable. As a result, it is necessary to combine several methods of analysis that contribute to a distinct categorization of taxa. This study aimed to raise diagnostic characters, both morphological and molecular, for the correct identification of species of the genus Chrysomya (Diptera: Calliphoridae) recorded in the New World, which has continuously generated discussion about its taxonomic position over the last century. A clear example of this situation was the first record of Chrysomya rufifacies in Brazilian territory in 2012. However, the morphological polymorphism and genetic variability of Chrysomya albiceps studied here show that both species (C. rufifacies and C. albiceps) share very similar character states, leading to misidentification and subsequent registration error of species present in our territory. This conclusion is demonstrated by the authors, based on a review of the material deposited in major scientific collections in Brazil and subsequent molecular and phylogenetic analysis of these samples. Additionally, we have proposed a new taxonomic key to separate the species of Chrysomya found on the American continent, taking into account a larger number of characters beyond those available in current literature.

Simplified flow cytometric assay to detect minimal residual disease in childhood with acute lymphoblastic leukemia

The detection of minimal residual disease (MRD) is an important prognostic factor in childhood acute lymphoblastic leukemia (ALL) providing crucial information on the response to treatment and risk of relapse. However, the high cost of these techniques restricts their use in countries with limited resources. Thus, we prospectively studied the use of flow cytometry (FC) with a simplified 3-color assay and a limited antibody panel to detect MRD in the bone marrow (BM) and peripheral blood (PB) of children with ALL. BM and PB samples from 40 children with ALL were analyzed on days (d) 14 and 28 during induction and in weeks 24-30 of maintenance therapy. Detectable MRD was defined as > 0.01% cells expressing the aberrant immunophenotype as characterized at diagnosis among total events in the sample. A total of 87% of the patients had an aberrant immunophenotype at diagnosis. On d14, 56% of the BM and 43% of the PB samples had detectable MRD. On d28, this decreased to 45% and 31%, respectively. The percentage of cells with the aberrant phenotype was similar in both BM and PB in T-ALL but about 10 times higher in the BM of patients with B-cell-precursor ALL. Moreover, MRD was detected in the BM of patients in complete morphological remission (44% on d14 and 39% on d28). MRD was not significantly associated to gender, age, initial white blood cell count or cell lineage. This FC assay is feasible, affordable and readily applicable to detect MRD in centers with limited resources.

Childhood and adolescent obesity and adult mortality: a systematic review of cohort studies

This systematic review addressed cohort studies on obesity in childhood and adolescence and adult mortality, published from January 1990 to March 2007. We searched the PubMed database with the following uniterms: obesity, mortality, child, adolescent; obesity and mortality; overweight and mortality. References were also analyzed. The age limit was 2 to 18 years. Quality of the articles was assessed, and eight were identified and reviewed. All used weight and stature for determination of obesity, and seven used body mass index (BMI). The quality score varied from 9 to 17. Evidence of association between obesity in childhood and adolescence and adult mortality should be viewed with caution. Use of BMI and potential confounders were discussed. Further research is needed to analyze the relationship between childhood and adolescent obesity and adult mortality.

Infant feeding practices, childhood growth and obesity in adult life

A saúde infantil é amplamente afetada pelo estado nutricional. Há um interesse crescente acerca da possibilidade do estado nutricional apresentado pela criança e das práticas alimentares na primeira infância estarem relacionados à obesidade em indivíduos adultos, aumentando os riscos para complicações metabólicas. Sabe-se que estudos prospectivos possibilitam a investigação e a avaliação apropriadas de determinantes do desenvolvimento infantil. Consequentemente, o presente artigo objetivou revisar as principais evidências disponíveis a partir de estudos longitudinais sobre associações entre práticas alimentares na primeira infância, padrões de crescimento infantil e estado nutricional verificados durante a vida adulta

Relationship between birthweight and arterial elasticity in childhood

There is a considerable debate about the potential influence of fetal programming on cardiovascular diseases in adulthood. In the present prospective epidemiological cohort study, the relationship between birthweight and arterial elasticity in 472 children between 5 and 8 years of age was assessed. LAEI (large artery elasticity index), SAEI (small artery elasticity index) and BP (blood pressure) were assessed using the HDI/PulseWave CR-2000 CardioVascular Profiling System. Blood concentrations of glucose, total cholesterol and its fractions [LDL (low-density lipoprotein)-cholesterol and HDL (high-density lipoprotein)-cholesterol] and triacylglycerols (triglycerides) were determined by automated enzymatic methods. Insulin was assessed by a chemiluminescent method, insulin resistance by HOMA (homoeostasis model assessment) and CRP (C-reactive protein) by immunonephelometry. Two linear regression models were applied to investigate the relationship between the outcomes, LAEI and SAEI, and the following variables: birthweight, gestational age, glucose, LDL-cholesterol, HDL-cholesterol, triacylglycerols, insulin, CRP, HOMA, age, gender, waist circumference, per capita income, SBP (systolic BP) and DBP (diastolic BP). LAEI was positively associated with birthweight (P=0.036), waist circumference (P<0.001) and age (P<0.001), and negatively associated with CRP (P=0.024) and SBP (P<0.001). SAEI was positively associated with birthweight (P=0.04), waist circumference (P=0.001) and age (P<0.001), and negatively associated with DBP (P<0.001). Arterial elasticity was decreased in apparently healthy children who had lower birthweights, indicating an earlier atherogenetic susceptibility to cardiovascular diseases in adolescence and adult life. Possible explanations for the results include changes in angiogenesis during critical phases of intrauterine life caused by periods of fetal growth inhibition and local haemodynamic anomalies

The relationship between cortisol concentrations in pregnancy and systemic vascular resistance in childhood

Objective. To assess the relationship between cortisol concentrations in the last trimester of pregnancy and systemic vascular resistance — SVR in childhood. Materials and methods. This study is part of a cohort involving 130 Brazilian pregnant women and their children, ages 5 to 7 years. Maternal cortisol was determined in saliva by an enzyme immunoassay utilizing the mean concentration of 9 samples of saliva (3 in each different day), collected at the same time, early in the morning. SVR was assessed by the HDI/PulseWave CR-2000 Cardiovascular Profiling System®. Socioeconomic and demographic characteristics and life style factors were determined by a questionnaire. The nutritional status of the women and children was assessed by the body mass index — BMI. The association between maternal cortisol and SVR in childhood was calculated by multivariate linear regression analysis. Results.There were statistically significant associations between maternal cortisol and SVR (p = 0.043) and BMI-z score of the children (p = 0.027), controlling for maternal BMI, birth weight, age, and gender of the children. Conclusion. As far as we know this is the first study in the literature assessing the association between cortisol concentrations in pregnancy and SVR in childhood. Overall, the data suggest that exposure to excess glucocorticoid in the prenatal period is associated to vascular complications in childhood, predisposing to cardiovascular diseases in later life