Polycyclic aromatic hydrocarbons in silicone wristbands of Uruguayan children: measurement and exposure source exploration.

Polycyclic aromatic hydrocarbons (PAHs) pose health risks to children, potentially resulting in stunted growth, obesity, and cognitive deficits, but lack of reliable and noninvasive means to measure PAHs results in poor understanding of exposure patterns and sources in this vulnerable population. In this study, 24 children aged ∼7 years (9 boys and 15 girls) from Montevideo, Uruguay wore silicone wristbands for 8 days to monitor the exposure of 27 PAHs. Wristbands were extracted using a modified ethyl acetate tandem solid phase extraction clean up and then analyzed via gas chromatography with tandem mass spectrometry. This analysis has reported LODs for 27 PAHs between 0.05 and 3.91 µg L-1. Eighteen PAHs were detected in >50% of the samples with concentration medians ranging 1.2-16.3 ng g-1 of wristband. Low molecular weight PAHs (2-3 rings) such as naphthalene and its alkyl derivatives were highly correlated (0.7-0.9) in the wristbands, suggesting exposure from related sources. Exposure source exploration focused on secondhand tobacco smoke, potentially through caregivers who reported on smoking habits in an associated survey. A principal components analysis (PCA) was conducted to examine patterns in PAH compounds detected in the wristbands; subsequently, the resulting components were compared according to current smoking among caregivers. The PCA analysis revealed a grouping of participants based on higher exposure of 1-methyl naphthalene, pyrene, fluoranthene, 1-methylphenanthrene, dibenzothiophene and 2-phenyl naphthalene. The derived components did relate with parental smoking, suggesting that some participants experienced exposure to a common source of certain PAHs outside of parental smoking. This is the first study to assess PAH exposure in young children from South America. Using wristbands, our study indicates exposure to multiple, potentially harmful chemicals. Wristbands could provide a comprehensive picture of PAH exposure in children, complementing other non-invasive biomonitoring approaches.

Enhancer Architecture and Essential Core Regulatory Circuitry of Chronic Lymphocytic Leukemia.

Enhancer profiling is a powerful approach for discovering cis-regulatory elements that define the core transcriptional regulatory circuits of normal and malignant cells. Gene control through enhancer activity is often dominated by a subset of lineage-specific transcription factors. By integrating measures of chromatin accessibility and enrichment for H3K27 acetylation, we have generated regulatory landscapes of chronic lymphocytic leukemia (CLL) samples and representative cell lines. With super enhancer-based modeling of regulatory circuits and assessments of transcription factor dependencies, we discover that the essential super enhancer factor PAX5 dominates CLL regulatory nodes and is essential for CLL cell survival. Targeting enhancer signaling via BET bromodomain inhibition disrupts super enhancer-dependent gene expression with selective effects on CLL core regulatory circuitry, conferring potent anti-tumor activity.

Combinations of topical fluoride (toothpastes, mouthrinses, gels, varnishes) versus single topical fluoride for preventing dental caries in children and adolescents.

BACKGROUND: Topical fluoride therapy (TFT) in the form of toothpastes, mouthrinses, varnishes and gels are effective caries preventive measures. However, there is uncertainty about the relative value of these interventions when used together. OBJECTIVES: To compare the effectiveness of two TFT modalities combined with one of them alone (mainly toothpaste) when used for the prevention of dental caries in children. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (May 2000), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2000), MEDLINE (1966 to January 2000), plus several other databases. We handsearched journals, reference lists of articles and contacted selected authors and manufacturers. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials with blind outcome assessment, comparing fluoride varnish, gel, mouthrinse, or toothpaste in combination with each other in children up to 16 years during at least 1 year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS). DATA COLLECTION AND ANALYSIS: Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party. Authors were contacted for missing data. The primary measure of effect was the prevented fraction (PF) that is the difference in mean caries increments between the 'treatment' and 'control' groups expressed as a percentage of the mean increment in the control group. Random effects meta-analyses were performed where data could be pooled. MAIN RESULTS: Eleven of the 12 included studies contributed data for the meta-analyses. For the nine trials that provided data for the main meta-analysis on the effect of fluoride mouthrinses, gels or varnishes used in combination with toothpaste (involving 4026 children) the D(M)FS pooled PF was 10% (95% CI, 2% to 17%; p = 0.01) in favour of the combined regimens. Heterogeneity was not substantial in these results (I square = 32%). The separate meta-analyses of fluoride gel or mouthrinse combined with toothpaste versus toothpaste alone favour the combined regimens, but differences were not statistically significant; the significant difference in favour of the combined use of fluoride varnish and toothpaste accrues from a very small trial and appears likely to be a spurious result. Not all other combinations of possible practical value were tested in the included studies. The only other statistically significant result was in favour of the combined use of fluoride gel and mouthrinse in comparison to gel alone (pooled DMFS PF 23%; 95% CI, 4% to 43%; p = 0.02), based on two trials. No other combinations of TFT were consistently superior to a single TFT. REVIEWER'S CONCLUSIONS: Topical fluorides (mouthrinses, gels, or varnishes) used in addition to fluoride toothpaste achieve a modest reduction in caries compared to toothpaste used alone. No conclusions about any adverse effects could be reached, because data were scarcely reported in the trials.

Fluoride mouthrinses for preventing dental caries in children and adolescents.

BACKGROUND: Fluoride mouthrinses have been used extensively as a caries-preventive intervention in school-based programmes and individually at home. OBJECTIVES: To determine the effectiveness and safety of fluoride mouthrinses in the prevention of dental caries in children and to examine factors potentially modifying their effect. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (May 2000), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2000), MEDLINE (1966 to January 2000), plus several other databases. We handsearched journals, reference lists of articles and contacted selected authors and manufacturers. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials with blind outcome assessment, comparing fluoride mouthrinse with placebo or no treatment in children up to 16 years during at least 1 year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS). DATA COLLECTION AND ANALYSIS: Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party. Authors were contacted for missing data. The primary measure of effect was the prevented fraction (PF) that is the difference in mean caries increments between the treatment and control groups expressed as a percentage of the mean increment in the control group. Random effects meta-analyses were performed where data could be pooled. Potential sources of heterogeneity were examined in random effects metaregression analyses. MAIN RESULTS: Thirty-six studies were included. For the 34 that contributed data for meta-analysis (involving 14,600 children) the D(M)FS pooled PF was 26% (95% confidence interval (CI), 23% to 30%; p < 0.0001). Heterogeneity was not substantial, but confirmed statistically (p = 0.008). No significant association between estimates of D(M)FS prevented fractions and baseline caries severity, background exposure to fluorides, rinsing frequency and fluoride concentration was found in metaregression analyses. A funnel plot of the 34 studies indicated no relationship between prevented fraction and study precision. There is little information concerning possible adverse effects or acceptability of treatment in the included trials. REVIEWER'S CONCLUSIONS: This review suggests that the supervised regular use of fluoride mouthrinse at two main strengths and rinsing frequencies is associated with a clear reduction in caries increment in children. In populations with caries increment of 0.25 D(M)FS per year, 16 children will need to use a fluoride mouthrinse (rather than a non-fluoride rinse) to avoid one D(M)FS; in populations with a caries increment of 2.14 D(M)FS per year, 2 children will need to rinse to avoid one D(M)FS. There is a need for complete reporting of side effects and acceptability data in fluoride mouthrinse trials.