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.

Legal disclosure of childhood sexual abuse: what can professionals tell us?

ABSTRACT: Purpose: This study explores how the decision to disclose Childhood Sexual Abuse (CSA) to the legal setting for adult victims is perceived by key informants, specifically factors that are believed to facilitate or prevent legal disclosure from occurring. Background: Prevalence rates of CSA are high (Pereda, Guilera, Forns & Gomez-Benito, 2009) and the negative consequences caused by the abuse acknowledged (Filipas & Ullman, 2006). Disclosure of this crime is understood to be complex and delayed disclosure recognised (Arata, 1998) but little is known about disclosure to the legal system. Rates of legal disclosure of CSA remain low and the attrition rates high (London, Bruck, Ceci & Shuman, 2005), but investigation and understanding of the contributory factors is rare. Disclosure of CSA to the legal system enables prosecution of the abuser and protection of the victim and others. Method: 10 “key informants” consisting of specialised clinicians working with adult victims of CSA were interviewed. Each informant completed an indepth interview exploring their beliefs about factors that facilitated or prevented adult victims of CSA from disclosing their experience to the legal system. Interviews were transcribed and the qualitative data subjected to Thematic Analysis. Conclusions: Two super-ordinate themes (Legal Disclosures Are Rare: “Why would they do that?” and The Anomalies: Acknowledging that this is a crime) and four sub-ordinate themes emerged from the analysis and an analytical narrative constructed. Themes emphasised the rarity of legal disclosure and the significant number of barriers adult victims of CSA perceive. Implications for clinical practice and future research are outlined.

Playgrounds going wrong: study of the adult style and children's rights during recess in an early childhood and primary education center

Recent perspectives on Pedagogy for Early Childhood Education emphasize children's participation in line with the Children's Rights Convention. The study aimed to analyse how children's rights are dealt with during recess in a school (Early Childhood and Primary Education) in Portugal. The aims were: to characterize the style of the adult (teaching assistants) and the interactions that are established with the children at the playground/recess, and analyse them in terms of children's rights. The qualitative approach was based on the observation during the recess for three weeks. The Adult Style Observation Schedule for Early Childhood Education (ASOS-ECE) was used to register and code the dynamics of six teaching assistants (3 ECE and 3 PE). Critical incidents were also registered. Statistical analysis of the ASOS-ECE levels were complemented with the content analysis of the notes. The playground space was quite limited and affected children's play and well-being. The outdoor playground was never used for the Early Childhood classes, only for Primary Education students but with little supervision. Children were often deprived of playground time by decision of the teaching assistants, as punishment. The results obtained through the Adult Style Observation Schedule for Early Childhood Education (ASOS-ECE) are not satisfactory and are below what would meet the minimum quality value (3,5). For Early Childhood Education, sensibility is the most valued dimension but with very low levels (<2,5). For Primary Education it was autonomy that scored highest (<2,5). The analysis of the notes/critical incidents highlighted articles 12 (expression of own views), 13 (freedom of expression), 19 (protection against violence), 29 (development of personality) and 31 (rest and leisure, play and recreational activities) as being put into question by actions of the adults responsible for the children. Children's rights and well-being need to be put forward in the knowledge base for all adults working with children so that Pedagogy can fulfil its purpose fully.