Recent exposure to ultrafine particles in school children alters miR-222 expression in the extracellular fraction of saliva

Background: Ultrafine particles (< 100 nm) are ubiquitous present in the air and may contribute to adverse cardiovascular effects. Exposure to air pollutants can alter miRNA expression, which can affect downstream signaling pathways. miRNAs are present both in the intracellular and extracellular environment. In adults, miR-222 and miR-146a were identified as associated with particulate matter exposure. However, there is little evidence of molecular effects of ambient air pollution in children. This study examined whether exposure to fine and ultrafine particulate matter (PM) is associated with changes in the extracellular content of miR-222 and miR-146a of children. Methods: Saliva was collected from 80 children at two different time points, circa 11 weeks apart and stabilized for RNA preservation. The extracellular fraction of saliva was obtained by means of differential centrifugation and ultracentrifugation. Expression levels of miR-222 and miR-146a were profiled by qPCR. We regressed the extracellular miRNA expression against recent exposure to ultrafine and fine particles measured at the school site using mixed models, while accounting for sex, age, BMI, passive smoking, maternal education, hours of television use, time of the day and day of the week. Results: Exposure to ultrafine particles (UFP) at the school site was positively associated with miR-222 expression in the extracellular fraction in saliva. For each IQR increase in particles in the class room (+8504 particles/cm(3)) or playground (+ 28776 particles/cm(3)), miR-222 was, respectively 23.5 % (95 % CI: 3.5 %-41.1 %; p = 0.021) or 29.9 % (95 % CI: 10.6 %-49.1 %; p = 0.0027) higher. No associations were found between miR-146a and recent exposure to fine and ultrafine particles. Conclusions: Our results suggest a possible epigenetic mechanism via which cells respond rapidly to small particles, as exemplified by miR-222 changes in the extracellular fraction of saliva

Immunoglobulin Heavy Chain High-Throughput Sequencing in Pediatric B-Precursor Acute Lymphoblastic Leukemia: Is the Clonality of the Disease at Diagnosis Related to Its Prognosis?

peer reviewedHigh-throughput sequencing (HTS) of the immunoglobulin heavy chain (IgH) locus is a recent very efficient technique to monitor minimal residual disease of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). It also reveals the sequences of clonal rearrangements, therefore, the multiclonal structure, of BCP-ALL. In this study, we performed IgH HTS on the diagnostic bone marrow of 105 children treated between 2004 and 2008 in Belgium for BCP-ALL in the European Organization for Research and Treatment of Cancer (EORTC)-58951 clinical trial. Patients were included irrespectively of their outcome. We described the patterns of clonal complexity at diagnosis and investigated its association with patients' characteristics. Two indicators of clonal complexity were used, namely, the number of foster clones, described as clones with similar D-N2-J rearrangements but other V-rearrangement and N1-joining, and the maximum across all foster clones of the number of evolved clones from one foster clone. The maximum number of evolved clones was significantly higher in patients with t(12;21)/ETV6:RUNX1. A lower number of foster clones was associated with a higher risk group after prephase and t(12;21)/ETV6:RUNX1 genetic type. This study observes that clonal complexity as accessed by IgH HTS is linked to prognostic factors in childhood BCP-ALL, suggesting that it may be a useful diagnostic tool for BCP-ALL status and prognosis

Quality of life of long-term childhood acute lymphoblastic leukemia survivors:Comparison with healthy controls

peer reviewed[en] OBJECTIVE: Improved treatment landscape has led to better outcomes for paediatric acute lymphoblastic leukemia (ALL) survivors. As the number of survivors increase, we need to elucidate the long-term quality of life (QoL) and domains of complaints in these patients. Furthermore, the main priorities of these patients need to be clarified. We assessed long-term QoL outcomes of survivors of childhood ALL compared to matched population controls. METHODS: QoL data were collected from survivors recruited in France and Belgium between 2012 and 2017, including the Short Form Health Survey (SF-12) and the Quality of Life Systemic Inventory (QLSI). The Wilcoxon test was used to compare SF-12 scale scores between survivors and matched population controls. For the QLSI, comparisons were mainly descriptive. RESULTS: One hundred and eighty-six survivors (mean age: 27.6 years; range: 18.1-52.8) at follow-up completed QoL measures, amongst whom 180 were matched to controls. Overall, survivors had higher QoL on all SF12 scale scores, indicating that they had better functioning compared to controls. Statistically significant differences on the SF12 were observed for Vitality, Social Functioning, Role Limitations due to Emotional Problems and Mental Health scales. QLSI outcomes suggested that survivors were happier than controls with Couple and Social Relations. Controls were unhappiest compared to survivors with Money, Love life, Self-esteem, Nutrition and Paid Work. CONCLUSIONS: Our findings suggest that survivors of childhood ALL have better QoL outcomes on some domains compared to the general population, specifically around social and emotional functioning, and that they tend to prioritize their relationships more. Interventions for improving QoL outcomes, might build on existing positive experiences with family, friends and partners

The posterior distribution of the RR in the meta-analyses of the associations between A) adding lidocaine and the risk of pain on injection of propofol, and B) pretreatment with lidocaine and the risk of pain on injection of propofol.

<p>The posterior distributions describe the knowledge about the RR. The higher the value of the density function, the more likely a given value of RR is in light of the prior knowledge (no prior knowledge was assumed) and the data from the meta-analysis. For both meta-analyses, there was much certainty that the RR was greater than 1, indicating that statistically significant results favoring the treatment had a greater probability of being included in the meta-analysis than other results. </p

How does underreporting of negative and inconclusive results affect the false positive rate in meta-analysis? A simulation study. R code

<p>The aim of this project was to perform simulations investigating the impact of a higher publishing probability for statistically significant positive outcomes on the validity of meta-analysis. The type I error rate for the test of the mean effect size (i.e., the rate at which meta-analyses showed that the mean effect differed from 0 when it in fact equaled 0) was estimated. Additionally, the power and type I error rate of publication bias detection methods based on the funnel plot were estimated. The simulations show that a higher probability of including statistically significant positive outcomes causes a severe increase of the false positive rate in meta-analysis. Moreover, a one-sided selection process based on the statistical significance of a sufficient magnitude to dramatically bias meta-analysis conclusions is poorly detectable by publication bias methods based on the funnel plot when the mean effect size equals 0. An annotated R program which was used to perform the simulations is available here.</p

Publication bias in meta-analyses of clinical trials.

<p>The RR is the ratio of the probability of including statistically significant results favoring the treatment to the probability of including other results. The median of the posterior distribution was used for point estimation. The interval estimate is the 95% equal-tail credible interval. P(RR>1) is the posterior probability that statistically significant results favoring the treatment had a higher chance of being included in the meta-analysis than other results.</p

The posterior distribution of the RR in the meta-analyses of the associations between A) c−reactive protein level and cardiovascular events and B) child physical abuse and depressive disorders.

<p>The posterior distributions describe the knowledge about the RR. The higher the value of the density function, the more likely a given value of RR is in light of the prior knowledge (no prior knowledge was assumed) and the data from the meta-analysis. For both meta-analyses, there was much certainty that the RR was greater than 1, indicating that plausible statistically significant results had a greater probability of being included in the meta-analysis than other results.</p