Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification

Functional diversity and co-operativity between subclonal populations of paediatric glioblastoma and diffuse intrinsic pontine glioma cells

The failure to develop effective therapies for pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) is in part due to their intrinsic heterogeneity. We aimed to quantitatively assess the extent to which this was present in these tumors through subclonal genomic analyses and to determine whether distinct tumor subpopulations may interact to promote tumorigenesis by generating subclonal patient-derived models in vitro and in vivo. Analysis of 142 sequenced tumors revealed multiple tumor subclones, spatially and temporally coexisting in a stable manner as observed by multiple sampling strategies. We isolated genotypically and phenotypically distinct subpopulations that we propose cooperate to enhance tumorigenicity and resistance to therapy. Inactivating mutations in the H4K20 histone methyltransferase KMT5B (SUV420H1), present in <1% of cells, abrogate DNA repair and confer increased invasion and migration on neighboring cells, in vitro and in vivo, through chemokine signaling and modulation of integrins. These data indicate that even rare tumor subpopulations may exert profound effects on tumorigenesis as a whole and may represent a new avenue for therapeutic development. Unraveling the mechanisms of subclonal diversity and communication in pGBM and DIPG will be an important step toward overcoming barriers to effective treatments

Ramadan Observance Is Associated with Impaired Kung-Fu-Specific Decision-Making Skills

The aim of the present study is to evaluate the effect of Ramadan observance (RAM) on decision-making in Kung-Fu athletes. Fourteen male Kung-Fu athletes (mean age = 19 ± 3 years) completed two test sessions: before Ramadan (BR) and at the end of Ramadan (ER). In the afternoon of each session (between 16:00 h and 18:00 h), participants completed: Epworth Sleepiness Scale (ESS), Profile of Mood States (POMS), and Pittsburg Sleep Quality Index (PSQI). Subjects also reported subjective fatigue, alertness, and concentration. Additionally, all participants performed video-based decision-making tasks (i.e., reaction time and decision-making). Results indicated that reaction time decreased by 30% at ER vs. BR (p < 0.01). However, decision-making decreased by 9.5% at ER vs. BR (p < 0.05). PSQI results indicated sleep quality score, sleep duration, and sleep efficiency were negatively affected at ER compared to BR (p < 0.05). ESS was higher at ER compared to BR (p < 0.05). In addition, fatigue scores, estimated by the POMS and current subjective feelings (i.e., fatigue, concentration, and alertness), were also negatively affected at ER compared to BR (p < 0.05). In conclusion, Ramadan observance was associated with an adverse effect on sleep and decision making, as well as feelings of fatigue, alertness, and concentration

Genetic Testing: Predictive Value Of Genotyping For Diagnosis And Management Of Disease

This article describes predictive, preventive value of genetic tests and the implication of the use of testing for personalized treatment. This year marks the 10th anniversity of publishing of the sequence of the human genome. One important area of application of this mega project is a development of genetic tests for mutation detection in single gene disorders that has impact for pediatric age group patients and analyzing susceptibility genes as risk factors in common disorders. Types of genetic tests, new emerging technologies will enable developments of high-throughput approaches by microarrays of great application capacity as described here. As it is usual for all technologies used in health care, bioethical concerns has to be delt with. The ethical, social and governance issues associated with genetic testing are discussed.PubMedScopu