Genome-wide methylation profiling identifies novel methylated genes in neuroblastoma tumors

Neuroblastoma is a very heterogeneous tumor of childhood. The clinical spectra range from very aggressive metastatic disease to spontaneous regression, even without therapy. Aberrant DNA methylation pattern is a common feature of most cancers. For neuroblastoma, it has been demonstrated both for single genes as well as genome-wide, where a so-called methylator phenotype has been described. Here, we present a study using Illumina 450K methylation arrays on 60 neuroblastoma tumors. We show that aggressive tumors, characterized by International Neuroblastoma Risk Group (INRG) as stage M, are hypermethylated compared to low-grade tumors. On the contrary, INRG stage L tumors display more non-CpG methylation. The genes with the highest number of hypermethylated CpG sites in INRG M tumors are TERT, PCDHGA4, DLX5, and DLX6-AS1. Gene ontology analysis showed a representation of neuronal tumor relevant gene functions among the differentially methylated genes. For validation, we used a set of independent tumors previously analyzed with the Illumina 27K methylation arrays, which confirmed the differentially methylated sites. Top candidate genes with aberrant methylation were analyzed for altered gene expression through the R2 platform (http://r2.amc.nl), and for correlations between methylation and gene expression in a public dataset. Altered expression in nonsurvivors was found for the genes B3GALT4 and KIAA1949, CLIC5, DLX6-AS, TERT, and PIRT, and strongest correlations were found for TRIM36, KIAA0513, and PIRT. Our data indicate that methylation profiling can be used for patient stratification and informs on epigenetically deregulated genes with the potential of increasing our knowledge about the underlying mechanisms of tumor development.     

Treatment during a developmental window prevents NF1-associated optic pathway gliomas by targeting Erk-dependent migrating glial progenitors

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Best Practice Guidelines in Pediatric/Adolescent Weight Loss Surgery

Objective: To establish evidence‐based guidelines for best practices in pediatric/adolescent weight loss surgery (WLS). Research Methods and Procedures: We carried out a systematic search of English‐language literature in MEDLINE on WLS performed on children and adolescents. Key words were used to narrow the field for a selective review of abstracts. Data were extracted, and evidence categories were assigned according to a grading system based on established evidence‐based models. Eight pertinent case series, published between 1980 and 2004, were identified and reviewed. These data were supplemented with expert opinions and literature on WLS in adults. Results: Recommendations focused on patient safety, reduction of medical errors, systems improvements, credentialing, and future research. We developed evidence‐based criteria for eligibility, assessment, treatment, and follow‐up; recommended surgical procedures based on the best available evidence; and established minimum guideline requirements for data collection. Discussion: Lack of adequate data and gaps in knowledge were cited as important reasons for caution. Physiological status, comprehensive screening of patients and their families, and required education and counseling were identified as key factors in assessing eligibility for surgery. Data collection and peer review were also identified as important issues in the delivery of best practice care.     

Association between pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections disease and tumor necrosis factor-α gene?308 g/a, ?850 c/t polymorphisms in 4-12-year-old children in Adana/Turkey

OBJECTIVES:

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a newly defined disease in neuropsychiatry and occurs with an autoimmune mechanism after Group A Beta Hemolytic Streptococcus (GABHS) infection. Tumor necrosis factor (TNF), encoded by TNF-α gene has an important role in the apoptotic mechanisms of autoimmune diseases. Recently, TNF-α polymorphisms and autoimmune/psychiatric disorders have been reported to be related. In this regard, we focused on to investigate a possible relation between the TNF-α gene promoter region−308 G/A and − 850 C/T polymorphisms and PANDAS.

MATERIALS AND METHODS:

In this study, ages of PANDAS patient and control groups were ranging from 4 years to 12-year-old. Patient group includes childhood onset PANDAS patients (n = 42) and control group includes healthy children (n = 58). Diagnoses have been carried out according to Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) criteria with Affective Disorders and Schizophrenia-Present and Lifetime (KSAD-S-PL) and Children Yale-Brown Obsessive Compulsive Scale Moreover, PANDAS criteria established by the American National Psychiatry Institute have been employed for diagnoses. For identifying polymorphisms; Polymerase Chain Reaction, Restriction Fragment Length Polymorphism and Polyacrylamid Gel Electrophoresis were used.

RESULTS AND DISCUSSION:

For −308 polymorphism, 37 of 42 PANDAS patients’ results and for −850 C/T polymorphism, 38 of 42 PANDAS patients’ results were obtained. According to our statistical analysis there is a positive relationship between PANDAS patients for −308 G/A polymorphism but not for −850 C/T polymorphism. There is no positive relationship between −308 G/A polymorphism and antistrep-tolysin O (ASO) titers and no relationship between −850 C/T polymorphism and ASO titers. We found, however, positive relationship between genders of patients (boys) and the disease. According to our results, we propose that the AA polymorphism of −308 G/A polymorphism can be used as a molecular indicator for PANDAS.     

Incidence and Factors Associated With Acne in Transgender Adolescents on Testosterone: A Retrospective Cohort Study

ObjectiveThis retrospective cohort study aimed to assess incidence and predictors of acne among transgender adolescents receiving testosterone.MethodsWe analyzed records of patients aged <18 years, assigned female at birth, seen at Children’s Healthcare of Atlanta Pediatric Endocrinology clinic for testosterone initiation between January 1, 2016, and January 1, 2019, with at least 1-year follow-up documented. Bivariable analyses to determine the association of clinical and demographic factors with new acne diagnosis were performed.ResultsOf 60 patients, 46 (77%) did not have baseline acne, but of those 46 patients, 25 (54%) developed acne within 1 year of testosterone initiation. Overall incidence proportion was 70% at 2 years; patients who used progestin prior to or during follow-up were more likely to develop acne than nonusers (92% vs 33%, P <.001).ConclusionTransgender adolescents starting testosterone, particularly those taking progestin, should be monitored for acne development and treated proactively by hormone providers and dermatologists.     

Prevalence and incidence of Helicobacter pylori Infection in a healthy pediatric population in the Lisbon area

Background: Helicobacter pylori is mainly acquired in childhood. Although adult studies reported a high prevalence of H. pylori infection in Portugal, the actual rate in children remains unknown. This study aimed to determine the prevalence and the incidence of H. pylori infection in an asymptomatic pediatric population of the Lisbon area and to correlate prevalence with sociodemographic determinants. Materials and Methods: Helicobacter pylori infection was determined by stool antigen test in 844 asymptomatic children (age 0–15 years; 49.4% boys). For the incidence study, H. pylori‐negative children in the prevalence study were followed‐up every 6 months over a 3‐year period. Results: The global prevalence of H. pylori infection was 31.6%, increasing with age (19.9, 37.0 and 51.5%, in age groups 0–5, 6–10, and 11–15, respectively), but was similar among genders (34.5% in boys and 28.4% in girls). Older age and attendance of nursery/kindergarten during preschool constituted independent risk factors. The overall estimated incidence was 11.6 per 100 child‐years (CY). Although 47.5% of children acquired H. pylori infection before 5 years of age, the mean age of acquisition was 6.3. The incidence of infection was similar among the three age groups (11.5, 13.0, and 10.5 per 100 CY, in age groups 0–5, 6–10, and 11–15, respectively). Conclusions: The prevalence of H. pylori infection in the Portuguese pediatric population is still high. Although this study confirmed that the highest acquisition rate occurs at young age, it showed that in high‐prevalence populations, older children can also acquire H. pylori infection at a rate similar to that of young children.     

Evaluation of home-based thermal biofeedback treatment of pediatric migraine headache

Sixteen children and adolescents with migraine headache were treated with thermal biofeedback. Seven were seen individually in the clinic while the other nine participated in a limited-contact, partly home-based regimen. Evaluation of headache diary data from 4-week monitoring periods before and after treatment showed significant (p<.01) reduction in headaches, with no significant difference in efficacy between the two conditions.This research was supported in part by grants from NIMH, MH-41341, and NINCDS, NS-23440.