The exposure of young children to accident risk as pedestrians

Pedestrian road accidents show a marked peak for children aged 5, 6 and 7 years with boys twice as involved as girls at these ages. Howarth et al (1974) described a framework in which measures of exposure were defined and related to the accident statistics to obtain estimates of absolute levels of risk for different categories of pedestrian in different traffic situations. The present paper describes a survey of children's exposure carried out to provide suitable data for this quantitative analysis. We interviewed a representative sample of Nottingham schoolchildren about their journeys in the previous 24 hours and recorded the number of roads crossed and the traffic densities of these roads. The measures of exposure obtained are presented in relation to the accompaniment of children on their journeys, the type of area in which they live, and time of day. Risk was assessed by relating exposure measures both to the national and local accident statistics. The analysis provides estimates of the risk to children of different ages and sex in their normal pattern of road crossing and in crossing roads of different traffic density and indicates that the accident statistics alone considerably underestimate the degree of risk to children under the age of eight. Interviews with a sample of the parents of the children suggest that children may provide a more accurate measure of their exposure than do their parents.     

Isomer-specific degradation and endocrine disrupting activity of nonylphenols

Degradation of technical nonylphenol by Sphingobium xenophagum Bayram led to a significant shift in the isomers composition of the mixture. By means of gas chromatography-mass spectrometry, we could observe a strong correlation between transformation of individual isomers and their alpha-substitution pattern, as expressed by their assignment to one of six mass spectrometric groups. As a rule, isomers with less bulkiness at the alpha-carbon and those with an optimally sized main alkyl chain (4-6 carbon atoms) were degraded more efficiently. By mass spectrometric analysis, we identified the two most recalcitrant main isomers of the technical mixture (Group 4) as 4-(1,2-dimethyl-1-propylbutyl)phenols (NP193a and NP193b), which are diastereomers with a bulky alpha-CH3, alpha-CH(CH3)C2H5 substitution. Our experiments with strain Bayram show that the selective enrichment of isomers with bulky alpha-substitutions observed in nonylphenol fingerprints of natural systems can be caused by microbial ipso-hydroxylation. Based on the yeast estrogen assay (YES), we established an estrogenicity ranking with a variety of single isomers and compared it to rankings obtained with different reporter cell systems. Structure-activity relationships derived from these data suggest that Group 4 isomers have a high estrogenic potency. This indicates a substantial risk that enrichment of highly estrogenic isomers during microbial degradation by ipso-substitution will increase the specific estrogenicity of aging material.     

Aflatoxin Exposure during Early Life Is Associated with Differential DNA Methylation in Two-Year-Old Gambian Children

Background: DNA methylation is an epigenetic control mechanism that may be altered by environmental exposures. We have previously reported that in utero exposure to the mycotoxin and liver carcinogen aflatoxin B1 from the maternal diet, as measured using biomarkers in the mothers’ blood, was associated with differential DNA methylation in white blood cells of 6-month-old infants from The Gambia. Methods: Here we examined aflatoxin B1-associated differential DNA methylation in white blood cells of 24-month-old children from the same population (n = 244), in relation to the child’s dietary exposure assessed using aflatoxin albumin biomarkers in blood samples collected at 6, 12 and 18 months of age. HM450 BeadChip arrays were used to assess DNA methylation, with data compared to aflatoxin albumin adduct levels using two approaches; a continuous model comparing aflatoxin adducts measured in samples collected at 18 months to DNA methylation at 24 months, and a categorical time-dose model that took into account aflatoxin adduct levels at 6, 12 and 18 months, for comparison to DNA methylation at 24 months. Results: Geometric mean (95% confidence intervals) for aflatoxin albumin levels were 3.78 (3.29, 4.34) at 6 months, 25.1 (21.67, 29.13) at 12 months and 49.48 (43.34, 56.49) at 18 months of age. A number of differentially methylated CpG positions and regions were associated with aflatoxin exposure, some of which affected gene expression. Pathway analysis highlighted effects on genes involved with with inflammatory, signalling and growth pathways. Conclusions: This study provides further evidence that exposure to aflatoxin in early childhood may impact on DNA methylation.     

Hodgkin's disease complicated by the nephrotic syndrome

A 12-year-old boy with nodular sclerosis Hodgkin's disease demonstrated nephrotic syndrome. A renal biopsy studied with light microscopy, electron microscopy, and immunofluorescence showed minimal change glomerulonephritis and some foci of fluorescence with anti-IgM. A literature review revealed that 35 cases of Hodgkin's disease with nephrotic syndrome have been reported. Possible etiologic mechanisms are discussed.     

Probing Bacterial Uptake of Glycosylated Ciprofloxacin Conjugates

Mono‐ and disaccharide‐functionalised conjugates of the fluoroquinolone antibiotic ciprofloxacin have been synthesised and used as chemical probes of the bacterial uptake of glycosylated ciprofloxacin. Their antimicrobial activities against a panel of clinically relevant bacteria were determined: the ability of these conjugates to inhibit their target DNA gyrase and to be transported into the bacteria was assessed by using in vivo and in vitro assays. The data suggest a lack of active uptake through sugar transporters and that although the addition of monosaccharides is compatible with the inhibition of DNA gyrase, the addition of a disaccharide results in a significant decrease in antimicrobial activity.