Effects of Benzopyrene-7,8-Diol-9,10-Epoxide (BPDE) In Vitro and of Maternal Smoking In Vivo on Micronuclei Frequencies in Fetal Cord Blood

Up to 20% of pregnant women smoke and there is indirect evidence that certain tobacco-specific metabolites can cross the placental barrier and are genotoxic to the fetus. The presence of micronuclei results from chromosome damage and reflects the degree of underlying genetic instability. Fetal blood was obtained from the cord blood of 143 newborns (102 from nonsmoking mothers and 41 from mothers smoking >10 cigarettes/d during pregnancy). The micronucleus assay was performed following the guidelines established by the Human MicroNucleus project with modifications. To test the micronucleus assay, we evaluated the effect of a range of benzopyrene-7,8-diol-9,10-epoxide concentrations (from 3.125 nM to 4 microM) on cord blood from nonsmoking mothers. This validation showed that the number of micronuclei and apoptotic cells increased with benzopyrene-7,8-diol-9,10-epoxide dose (p < 0.0001 and p = 0.001, respectively); the minimal detectable effect was induced by 12.5 nM benzopyrene-7,8-diol-9,10-epoxide. In our sample, the number of MN was significantly higher in the 41 cord blood samples from mothers who smoked during pregnancy [smokers: 4 (1; 10.5); nonsmokers: 3 (0; 8); p = 0.016]. Therefore, the data reported herein support the hypothesis that tobacco compounds are able to induce chromosomal losses and breaks that are detectable as an increased number of micronuclei

A common framework for approaches to extreme event attribution

The extent to which a given extreme weather or climate event is attributable to anthropogenic climate change is a question of considerable public interest. From a scientific perspective, the question can be framed in various ways, and the answer depends very much on the framing. One such framing is a risk-based approach, which answers the question probabilistically, in terms of a change in likelihood of a class of event similar to the one in question, and natural variability is treated as noise. A rather different framing is a storyline approach, which examines the role of the various factors contributing to the event as it unfolded, including the anomalous aspects of natural variability, and answers the question deterministically. It is argued that these two apparently irreconcilable approaches can be viewed within a common framework, where the most useful level of conditioning will depend on the question being asked and the uncertainties involved

Immune function biomarkers in children exposed to lead and organochlorine compounds: a cross-sectional study

BACKGROUND: Different organochlorines and lead (Pb) have been shown to have immunomodulating properties. Children are at greater risk for exposure to these environmental toxicants, but very little data exist on simultaneous exposures to these substances. METHODS: We investigated whether the organochlorine compounds (OC) dichlorodiphenylethylene (DDE), hexachlorobenzene (HCB), hexachlorocyclohexane (γ-HCH), the sum of polychlorinated biphenyls (ΣPCBs) and Pb were associated with immune markers such as immunoglobulin (Ig) levels, white blood cell (WBC), counts of lymphocytes; eosinophils and their eosinophilic granula as well as IgE count on basophils. The investigation was part of a cross-sectional environmental study in Hesse, Germany. In 1995, exposure to OC and Pb were determined, questionnaire data collected and immune markers quantified in 331 children. For the analyses, exposure (OC and Pb) concentrations were grouped in quartiles (γ-HCH into tertiles). Using linear regression, controlling for age, gender, passive smoking, serum lipids, and infections in the previous 12 months, we assessed the association between exposures and immune markers. Adjusted geometric means are provided for the different exposure levels. RESULTS: Geometric means were: DDE 0.32 μg/L, ΣPCBs 0.50 μg/L, HCB 0.22 μg/L, γ-HCH 0.02 μg/L and Pb 26.8 μg/L. The ΣPCBs was significantly associated with increased IgM levels, whereas HCB was inversely related to IgM. There was a higher number of NK cells (CD56+) with increased γ-HCH concentrations. At higher lead concentrations we saw increased IgE levels. DDE showed the most associations with significant increases in WBC count, in IgE count on basophils, IgE, IgG, and IgA levels. DDE was also found to significantly decrease eosinophilic granula content. CONCLUSION: Low-level exposures to OC and lead (Pb) in children may have immunomodulating effects. The increased IgE levels, IgE count on basophils, and the reduction of eosinophilic granula at higher DDE concentrations showed a most consistent pattern, which could be of clinical importance in the etiology of allergic diseases

Parental smoking and childhood cancer: results from the United Kingdom Childhood Cancer Study

There are strong a priori reasons for considering parental smoking behaviour as a risk factor for childhood cancer but case – control studies have found relative risks of mostly only just above one. To investigate this further, self-reported smoking habits in parents of 3838 children with cancer and 7629 control children included in the United Kingdom Childhood Cancer Study (UKCCS) were analysed. Separate analyses were performed for four major groups (leukaemia, lymphoma, central nervous system tumours and other solid tumours) and more detailed diagnostic subgroups by logistic regression. In the four major groups, after adjustment for parental age and deprivation there were nonsignificant trends of increasing risk with number of cigarettes smoked for paternal preconception smoking and nonsignificant trends of decreasing risk for maternal preconception smoking (all P-values for trend >0.05). Among the diagnostic subgroups, a statistically significant increased risk of developing hepatoblastoma was found in children whose mothers smoked preconceptionally (OR=2.68, P=0.02) and strongest (relative to neither parent smoking) for both parents smoking (OR=4.74, P=0.003). This could be a chance result arising from multiple subgroup analysis. Statistically significant negative trends were found for maternal smoking during pregnancy for all diagnoses together (P<0.001) and for most individual groups, but there was evidence of under-reporting of smoking by case mothers. In conclusion, the UKCCS does not provide significant evidence that parental smoking is a risk factor for any of the major groups of childhood cancers

Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia

Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p<0.001). Infants treated with TH had lower peak Alanine aminotransferase (ALT) concentrations (p=0.025) and delay in reaching peak CRP concentration (p<0.001).  Conclusion: We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury

Anthropogenic intensification of short-duration rainfall extremes

Short- duration (1-3 h) rainfall extremes can cause serious damage to societies through rapidly developing (flash) flooding and are determined by complex, multifaceted processes that are altering as Earth's climate warms. In this Review, we examine evidence from observational, theoretical and modelling studies for the intensification of these rainfall extremes, the drivers and the impact on flash flooding. Both short- duration and long- duration (\textgreater1 day) rainfall extremes are intensifying with warming at a rate consistent with the increase in atmospheric moisture (~7% K-1), while in some regions, increases in short- duration extreme rainfall intensities are stronger than expected from moisture increases alone. These stronger local increases are related to feedbacks in convective clouds, but their exact role is uncertain because of the very small scales involved. Future extreme rainfall intensification is also modulated by changes to temperature stratification and large- scale atmospheric circulation. The latter remains a major source of uncertainty. Intensification of short- duration extremes has likely increased the incidence of flash flooding at local scales and this can further compound with an increase in storm spatial footprint to considerably increase total event rainfall. These findings call for urgent climate change adaptation measures to manage increasing flood risks