Ab initio molecular dynamics simulations of Aluminum solvation

The solvation of Al and its hydrolyzed species in water clusters has been studied by means of ab initio molecular dynamics simulations. The hexa-hydrate aluminum ion formed a stable complex in the finite temperature cluster simulation of one aluminum ion and 16 waters. The average dipole moment of strongly polarized hydrated water molecules in the first solvation shell of the hexa-hydrate aluminum ion was found to be 5.02 Debye. The deprotonated hexa-hydrate complex evolves into a tetra-coordinated aluminate ion with two water molecules in the second solvation shell forming hydrogen bonds to the hydroxyl groups in agreement with the observed coordination.Comment: 12 pages in Elsevier LaTeX, 5 figures in Postscript, 2 last figures are in color, submitted to Chemical Physics Letter

Lower risk of lung cancer after multiple pneumonia diagnoses

Although pneumonia has been suggested as a risk factor for lung cancer, previous studies have not evaluated the influence of number of pneumonia diagnoses in relation to lung cancer risk

Mood Disorders and Risk of Lung Cancer in the EAGLE Case-Control Study and in the U.S. Veterans Affairs Inpatient Cohort

Background: Mood disorders may affect lung cancer risk. We evaluated this hypothesis in two large studies. Methodology/Principal Findings: We examined 1,939 lung cancer cases and 2,102 controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study conducted in Italy (2002-2005), and 82,945 inpatients with a lung cancer diagnosis and 3,586,299 person-years without a lung cancer diagnosis in the U.S. Veterans Affairs Inpatient Cohort (VA study), composed of veterans with a VA hospital admission (1969-1996). In EAGLE, we calculated odds ratios (ORs) and 95% confidence intervals (CI), with extensive adjustment for tobacco smoking and multiple lifestyle factors. In the VA study, we estimated lung cancer relative risks (RRs) and 95% CIs with time-dependent Poisson regression, adjusting for attained age, calendar year, hospital visits, time within the study, and related previous medical diagnoses. In EAGLE, we found decreased lung cancer risk in subjects with a personal history of mood disorders (OR: 0.59, 95% CI: 0.44-0.79, based on 121 lung cancer incident cases and 192 controls) and family history of mood disorders (OR: 0.62, 95% CI: 0.50-0.77, based on 223 lung cancer cases and 345 controls). The VA study analyses yielded similar results (RR: 0.74, 95% CI: 0.71-0.77, based on 2,304 incident lung cancer cases and 177,267 non-cancer person-years) in men with discharge diagnoses for mood disorders. History of mood disorders was associated with nicotine dependence, alcohol and substance use and psychometric scales of depressive and anxiety symptoms in controls for these studies. Conclusions/Significance: The consistent finding of a relationship between mood disorders and lung cancer risk across two large studies calls for further research into the complex interplay of risk factors associated with these two widespread and debilitating diseases. Although we adjusted for smoking effects in EAGLE, residual confounding of the results by smoking cannot be ruled out

Analysis of Exposure-Time-Response Relationships Using a Spline Weight Function.

To examine the time-dependent effects of exposure histories on disease, we estimate a weight function within a generalized linear model. The shape of the weight function, which is modeled as a cubic B-spline, gives information about the impact of exposure increments at different times on disease risk. The method is evaluated in a simulation study and is applied to data on smoking histories and lung cancer from a recent case-control study in Germany

GSTM1 and GSTT1 copy numbers and mRNA expression in lung cancer

Large fractions of the human population do not express GSTM1 and GSTT1 (GSTM1/T1) enzymes because of deletions in these genes. These variations affect xenobiotic metabolism and have been evaluated in relation to lung cancer risk, mostly based on null/present gene models. We measured GSTM1/T1 heterozygous deletions, not tested in genome-wide association studies, in 2,120 controls and 2,100 cases from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We evaluated their effect on mRNA expression on lung tissue and peripheral blood samples and their association with lung cancer risk overall and by histology types. We tested the null/present, dominant, and additive models using logistic regression. Cigarette smoking and gender were studied as possible modifiers. Gene expression from blood and lung tissue cells was strongly down regulated in subjects carrying GSTM1/T1 deletions by both trend and dominant models (P\u2009<\u20090.001). In contrast to the null/present model, analyses distinguishing subjects with 0, 1, or 2 GSTM1/T1 deletions revealed several associations. There was a decreased lung cancer risk in never-smokers (OR\u2009=\u20090.44; 95%CI\u2009=\u20090.23-0.82; P\u2009=\u20090.01) and women (OR\u2009=\u20090.50; 95%CI\u2009=\u20090.28-0.90; P\u2009=\u20090.02) carrying 1 or 2 GSTM1 deletions. Analogously, male smokers had an increased risk (OR\u2009=\u20091.13; 95%CI\u2009=\u20091.0-1.28; P\u2009=\u20090.05) and women a decreased risk (OR\u2009=\u20090.78; 95%CI\u2009=\u20090.63-0.97; P\u2009=\u20090.02) for increasing GSTT1 deletions. The corresponding gene smoking and gene-gender interactions were significant (P\u2009<\u20090.05). Our results suggest that decreased activity of GSTM1/T1 enzymes elevates lung cancer risk in male smokers, likely due to impaired carcinogens' detoxification. A protective effect of the same mutations may be operative in never-smokers and women, possibly because of reduced activity of other genotoxic chemicals. \ua9 2012 Wiley Periodicals, Inc

The exposure-time-response relationship between occupational asbestos exposure and lung cancer in Two German case-control studies.

BACKGROUND: Numerous studies have been carried out to evaluate the association between lung cancer and occupational asbestos exposure. However, the effects of timing of exposure have not been analyzed thoroughly. METHODS: Two German case-control studies with data on occupational asbestos exposure histories have been pooled. Duration of work in potentially asbestos exposed jobs and two derived weighted exposure measures are analyzed together with time since last exposure. A spline function is used to model the effect of time since exposure. RESULTS: The odds ratios (OR) and corresponding 95% confidence intervals were 1.8 (1.2, 2.7) and 2.4 (1.7, 3.4) for subjects having worked for 3 to 7 years and 8 or more years, respectively, in a job with potential asbestos exposure compared to never-exposed. Based on an evaluation of time since last exposure, the OR decreased significantly to about one-half after more than 20 years since exposure ceased. Using a spline function, applied to workers&#39; complete exposure histories, the effect of an increment of exposure is greatest 10-15 years after that exposure was received. CONCLUSIONS: In contrast to previous indications, the risk of lung cancer increases soon after asbestos exposure, with its maximum effect from 10 to 15 years after the exposure was received. &nbsp