Epigenetic landscape correlates with genetic subtype but does not predict outcome in childhood acute lymphoblastic leukemia

Although children with acute lymphoblastic leukemia (ALL) generally have a good outcome, some patients do relapse and survival following relapse is poor. Altered DNA methylation is highly prevalent in ALL and raises the possibility that DNA methylation-based biomarkers could predict patient outcome. In this study, genome-wide methylation analysis, using the Illumina Infinium HumanMethylation450 BeadChip platform, was carried out on 52 diagnostic patient samples from 4 genetic subtypes [ETV6-RUNX1, high hyperdiploidy (HeH), TCF3-PBX1 and dic(9;20)(p11–13;q11)] in a 1:1 case-control design with patients who went on to relapse (as cases) and patients achieving long-term remission (as controls). Pyrosequencing assays for selected loci were used to confirm the array-generated data. Non-negative matrix factorization consensus clustering readily clustered samples according to genetic subgroups and gene enrichment pathway analysis suggested that this is in part driven by epigenetic disruption of subtype specific signaling pathways. Multiple bioinformatics approaches (including bump hunting and individual locus analysis) were used to identify CpG sites or regions associated with outcome. However, no associations with relapse were identified. Our data revealed that ETV6-RUNX1 and dic(9;20) subtypes were mostly associated with hypermethylation; conversely, TCF3-PBX1 and HeH were associated with hypomethylation. We observed significant enrichment of the neuroactive ligand-receptor interaction pathway in TCF3-PBX1 as well as an enrichment of genes involved in immunity and infection pathways in ETV6-RUNX1 subtype. Taken together, our results suggest that altered DNA methylation may have differential impacts in distinct ALL genetic subtypes.     

中美生物医学合作研究计划及其前景

中美生物医学合作研究计划实施3年来,收到了来自中美双方科学家共657项申请.这些申请在研究内容上涉及肿瘤、感染性疾病(包括HIV感染和艾滋病相关研究)、过敏性疾病、医学免疫学、精神健康及神经性疾病(中风和帕金森病).经过国家自然科学基金委员会和美国国立卫生研究院的联合评审程序,有109项申请项目获得了资助.联合评审的机制和获资助的109个研究项目的合作研究为今后中美双方的进一步合作奠定了基础.     

X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology

Mutations in the creatine transporter gene, SLC6A8 (MIM 30036), located in Xq28, have been found in families with X-linked mental retardation (XLMR) as well as in males with idiopathic mental retardation (MR). In order to estimate the frequency of such mutations in the MR population, a screening of 478 males with MR of unknown cause was undertaken. All 13 exons of SLC6A8 were sequenced using genomic DNA. Six novel potentially pathogenic mutations were identified that were not encountered in at least 588 male control chromosomes: two deletions (p.Asn336del, p.Ile347del) and a splice site alteration (c.1016+2C>T) are considered pathogenic based on the nature of the variant. A mutation (p.Arg391Trp) should be considered pathogenic owing to its localization in a highly conserved region. Two other missense variants (p.Lys4Arg, p.Gly26Arg) are not conserved but were not observed in over 300 male control chromosomes. Their pathogenicity is uncertain. A missense variant (p.Val182Met), was classified as a polymorphism based on a normal creatine/creatinine (Cr:Crn) ratio and cerebral creatine signal in proton magnetic resonance spectroscopy (H-MRS) in the patient. Furthermore, we found 14 novel intronic and neutral variants that were not encountered in at least 280 male control chromosomes and should be considered as unclassified variants. Our findings of a minimum of four pathogenic mutations and two potentially pathogenic mutations indicate that about 1% of males with MR of unknown etiology might have a SLC6A8 mutation. Thus, DNA sequence analysis and/or a Cr:Crn urine screen is warranted in any male with MR of unknown cause.Amy J. Clark and Efraim H. Rosenberg have contributed equally to this work.     

Lexical–semantic priming effects during infancy

When and how do infants develop a semantic system of words that are related to each other? We investigated word–word associations in early lexical development using an adaptation of the inter-modal preferential looking task where word pairs (as opposed to single target words) were used to direct infants’ attention towards a target picture. Two words (prime and target) were presented in quick succession after which infants were presented with a picture pair (target and distracter). Prime–target word pairs were either semantically and associatively related or unrelated; the targets were either named or unnamed. Experiment 1 demonstrated a lexical–semantic priming effect for 21-month olds but not for 18-month olds: unrelated prime words interfered with linguistic target identification for 21-month olds. Follow-up experiments confirmed the interfering effects of unrelated prime words and identified the existence of repetition priming effects as young as 18 months of age. The results of these experiments indicate that infants have begun to develop semantic–associative links between lexical items as early as 21 months of age.     

Integration of child mental health services to primary care: challenges and opportunities

In the first decade of this new millennium, health professionals are faced with a rapidly increasing need for child mental health services and changing models of service provision. This gives us a unique opportunity to make provision for services where it has not been available before, or to improve upon the existing services. This paper examines the challenges and opportunities while attempting to integrate child mental health services to primary care.     

Balint groups as 'shared care' in the area of mental health in primary medicine

This paper describes how Balint groups can be effective for primary care doctors and how leaders of these groups can act as role models in the interdisciplinary, experiential learning experience. The paper describes the way Balint activity helps the facilitation of a dialogue between mental health professionals and primary care physicians. While these groups have been found to improve the sensitivity of doctors in their interaction with patients, Balint groups, with the joint leadership of professionals from different disciplines, can be seen as an effective method to improve primary care and mental health cooperation. These issues are discussed and appropriate examples outlined offering an uncommon perspective on an interesting topic to promote an integrated, shared model of care.     

Dream work with children: Perceptions and practices of school mental health professionals.

In this study, 49 public school mental health practitioners (school counselors, school psychologists, and school social workers) completed a survey about working with students’ dreams. The majority of these practitioners reported having at least one student bring up dreams during counseling, more frequently with troubling dreams and nightmares or when coping with grief. Results showed that practitioners were less likely to talk about dreams with students who had been identified with an adjustment disorder, psychosis, or eating disorder; those who were oppositional or ill; and those who struggled with substance abuse problems. Although most practitioners did not feel competent working with children’s dreams and reported minimal training in dream work, they were interested in learning more about children’s dreams and potential uses of dream work in supportive counseling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Confronting and coping with weight stigma: an investigation of overweight and obese adults

Objective: This study examined experiences of weight stigmatization, sources of stigma, coping strategies, psychological functioning, and eating behaviors in a sample of 2671 overweight and obese adults. Research Methods and Procedures: The total sample was partitioned into two subsamples for investigation. Sample I was comprised of 2449 adult women, and Sample II was a matched sample of adult men and women (N = 222) that was disaggregated to investigate gender differences. Both samples completed an online battery of self‐report questionnaires measuring frequency of weight stigmatization and coping responses to deal with bias, the most common sources of the bias, symptoms of depression, self‐esteem, attitudes about weight and obesity, and binge eating behaviors. Results: Experiences of weight stigmatization, in many forms and across multiple occasions, was common in both samples. A variety of coping strategies were used in response. More frequent exposure to stigma was related to more attempts to cope and higher BMI. Physicians and family members were the most frequent sources of weight bias reported. No gender differences were observed in types or frequency of stigmatization. Frequency of stigmatization was not related to current psychological functioning, although coping responses were associated with emotional well‐being. Discussion: These findings raise questions about the relationship between stigma and psychological functioning and have important implications for obesity treatment and stigma reduction intervention efforts, both of which are discussed.     

伊曲康唑联合外用药物治疗花斑糠疹临床研究

目的探讨伊曲康唑胶囊联合1%盐酸布替萘芬乳膏和2%酮康唑洗剂治疗花斑糠疹的疗效及不良反应。方法入选患者按单双日分为两组,两组均口服伊曲康唑0.2g,1次/d,连续7d,同时外用1%盐酸布替萘芬乳膏,1次/d,连续14d,对照组停药观察,试验组同时使用2%酮康唑洗剂洗浴,每周2次,连用3个月。分别于治疗前、治疗后1、3、6、12个月评价疗效。结果试验组114例患者3个月时痊愈率78.1%,6个月时痊愈率90.4%,对照组125例患者3个月时痊愈率72.8%,6个月时痊愈率75.2%,12个月后试验组复发率1.8%,对照组为18.4%。结论伊曲康唑胶囊短时口服联合外用布替萘芬和酮康唑洗剂洗浴疗效较好,安全性高,使用方便,可大大降低花斑糠疹的复发率。