Evacuation decisions in a chemical air pollution incident: cross sectional survey.

OBJECTIVE: To compare the health outcomes in sheltered and evacuated populations after a chemical incident in a plastics factory. DESIGN: Cross sectional survey. SETTING: Urban area in southwest England. PARTICIPANTS: 1750 residents from the area exposed to the chemical smoke, of which 472 were evacuated and the remaining 1278 were advised to shelter indoors. MAIN OUTCOME MEASURE: Number of adverse health symptoms. A case was defined by the presence of four or more symptoms. MAIN RESULTS: 1096 residents (63%; 299 evacuated, 797 sheltered) provided data for analyses. The mean symptom score and proportion of cases were higher in evacuated people than in the sheltered population (evacuated: symptom score 1.9, cases 19.7% (n = 59); sheltered: symptom score 1.0, cases 9.5% (n = 76); P < 0.001 for both). The difference between the two groups attenuated markedly at the end of two weeks from the start of the incident. The two main modifiable risk factors for the odds of becoming a case were evacuation (odds ratio 2.5, 95% confidence interval 1.7 to 3.8) and direct exposure to smoke for more than two hours on the first day of the incident (2.0, 1.7 to 2.3). The distance of residence from the factory or level of exposure before intervention (first six hours) had little effect on the odds of a person becoming a case. CONCLUSIONS: Sheltering may have been a better protective action than evacuation in this chemical incident, which is consistent with the prevailing expert view. Although this study has limitations, it is based on a real event. Evacuations carry their own risks and resource implications; increased awareness may help to reduce unnecessary evacuations in the future

Isoxazole-Derived Amino Acids are Bromodomain-Binding Acetyl-Lysine Mimics: Incorporation into Histone H4 Peptides and Histone H3.

A range of isoxazole-containing amino acids was synthesized that displaced acetyl-lysine-containing peptides from the BAZ2A, BRD4(1), and BRD9 bromodomains. Three of these amino acids were incorporated into a histone H4-mimicking peptide and their affinity for BRD4(1) was assessed. Affinities of the isoxazole-containing peptides are comparable to those of a hyperacetylated histone H4-mimicking cognate peptide, and demonstrated a dependence on the position at which the unnatural residue was incorporated. An isoxazole-based alkylating agent was developed to selectively alkylate cysteine residues in situ. Selective monoalkylation of a histone H4-mimicking peptide, containing a lysine to cysteine residue substitution (K12C), resulted in acetyl-lysine mimic incorporation, with high affinity for the BRD4 bromodomain. The same technology was used to alkylate a K18C mutant of histone H3.Pfizer Neusentis for studentship suppor

Investigation of the Acetylation Mechanism by GCN5 Histone Acetyltransferase

The histone acetylation of post-translational modification can be highly dynamic and play a crucial role in regulating cellular proliferation, survival, differentiation and motility. Of the enzymes that mediate post-translation modifications, the GCN5 of the histone acetyltransferase (HAT) proteins family that add acetyl groups to target lysine residues within histones, has been most extensively studied. According to the mechanism studies of GCN5 related proteins, two key processes, deprotonation and acetylation, must be involved. However, as a fundamental issue, the structure of hGCN5/AcCoA/pH3 remains elusive. Although biological experiments have proved that GCN5 mediates the acetylation process through the sequential mechanism pathway, a dynamic view of the catalytic process and the molecular basis for hGCN5/AcCoA/pH3 are still not available and none of theoretical studies has been reported to other related enzymes in HAT family. To explore the molecular basis for the catalytic mechanism, computational approaches including molecular modeling, molecular dynamic (MD) simulation and quantum mechanics/molecular mechanics (QM/MM) simulation were carried out. The initial hGCN5/AcCoA/pH3 complex structure was modeled and a reasonable snapshot was extracted from the trajectory of a 20 ns MD simulation, with considering post-MD analysis and reported experimental results. Those residues playing crucial roles in binding affinity and acetylation reaction were comprehensively investigated. It demonstrated Glu80 acted as the general base for deprotonation of Lys171 from H3. Furthermore, the two-dimensional QM/MM potential energy surface was employed to study the sequential pathway acetylation mechanism. Energy barriers of addition-elimination reaction in acetylation obtained from QM/MM calculation indicated the point of the intermediate ternary complex. Our study may provide insights into the detailed mechanism for acetylation reaction of GCN5, and has important implications for the discovery of regulators against GCN5 enzymes and related HAT family enzymes

Should children with developmental and behavioural problems be routinely screened for lead?

AIM—To test the hypothesis that children with behavioural and/or developmental problems have significantly higher blood lead concentrations than the general childhood population.
METHODS—Blood samples were taken from 69 children with behavioural and/or developmental problems and 136 controls (children admitted for elective day case surgery under general anaesthetic). Blood lead estimations were carried out using graphite furnace atomic absorption
RESULTS—Children with behavioural and/or developmental problems had higher lead concentrations than controls, both in terms of their distribution across the group (mean(geometric) lead concentrations: 40.7 (cases), 29.2 (controls), ratio of the means(geometric) 1.35(95% CI 1.17, 1.58)) and the proportion of children with lead concentrations above those commonly defined as "toxic"—that is, 100 µg/l (12% (cases), 0.7% (controls); p < 0.001). Multiple linear regression suggested that this difference was not explained by differences in age, sex, or socioeconomic status of the two comparison groups.
CONCLUSIONS—Children with behavioural and/or developmental problems are more likely to have significantly higher blood lead concentrations than the general childhood population. Lead, a known and more importantly, a treatable neurotoxin, would further contribute to the impairment suffered by these children. We argue that this group of children should be routinely screened for lead.