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White matter hyperintensities (WMHs) are prevalent in the older adult and are often accompanied by cognitive decline and an increased risk of dementia. However, the roles of WMHs in the periventricular white matter and deep white matter regions in the aging process remain controversial. This study aimed to investigate the WMH burden across the adult lifespan and determine the interrelationships among age, WMH, and cognition. The present study included 312 healthy individuals aged 21-89 years who received structural magnetic resonance imaging and cognitive assessments. Periventricular WMH (PVWMH) and deep WMH (DWMH) volumes were computed and fitted using different regression models to evaluate the trajectory of WMH changes across the lifespan. Our findings support that the changes in WMH volume in the healthy population follow a nonlinear pattern with age, especially in PVWMH. With 2-mediator mediation analysis, we further suggest that the effect of age on the cognitive performance is mediated only by PVWMH. Conclusively, the increased PVWMH, but not DWMH, plays a major role in predicting cognitive aging in healthy adults., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The role of oxidative stress and systemic inflammation on the association between personal exposures to ambient fine particulate matter ≤ 2.5 μm in diameter (PM2.5) and cardiac autonomic dysfunction, indicated by reduction in heart rate variability (HRV), has not been examined., Methods: We performed a repeated measures study on community adults in a densely populated inner city neighborhood in Boston, Massachusetts. Continuous ambulatory electrocardiogram (ECG) monitoring and personal exposure to PM2.5 were measured for up to two consecutive days. Peripheral blood and spot urine samples were collected at 12-hour intervals for the measurements of markers of inflammation including C-reactive protein (CRP), fibrinogen, white blood cell (WBC) and platelet counts as well as for the analysis of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage., Results: After adjusting for confounders, we found a pronounced decrease in nighttime standard deviation of normal-to normal intervals (SDNN): an interquartile range (IQR) increase in PM2.5 (13.6 μg/m(3)) was associated with an 8.4% decrease in SDNN (95% CI: -11.3 to -5.5). Compared with the lower eightieth percentile, significantly greater PM2.5 associated nighttime SDNN reductions were observed among subjects in the upper twentieth percentile of 8-OHdG by -25.3%, CRP by -24.9%, fibrinogen by -28.7%, WBC by -23.4%, and platelet counts by -24.0% (all P<0.0001; all P interaction<0.01)., Conclusions: These data suggest that oxidative stress and systemic inflammation exacerbate the adverse effects of PM2.5 on the cardiac autonomic function even at ambient levels of exposure., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: We investigated the clinical significance of tumor markers in patients with silicosis., Methods: Eighty silicosis patients without malignancy and 50 healthy volunteers were compared for serum tumor marker concentrations. Pulmonary function and several routine laboratory tests were performed. Correlation between serum tumor marker concentrations and severity markers for silicosis was analyzed. Tumor marker concentrations were detected in both blood and BALF samples in silicosis patients. The pre- and post-lavage differences in the serum tumor marker concentrations were also investigated. Immunohistochemical staining for tumor markers was performed in a lung biopsy specimen from a silicosis patient., Results: Both serum NSE and CA125 concentrations were significantly higher in cases compared with controls. Significant positive correlations were found between values of NSE and CA125 and LDH concentration. Significant negative correlations were also observed between values of NSE and CA125 and spirometric parameters. Patients with silicosis had higher concentrations of NSE in BALF than that in serum. 11 of 14 patients experienced a decrease in NSE concentrations following whole lung lavage. Immunohistochemical studies showed positive NSE staining in lung biopsy specimen., Conclusions: Serum NSE and CA125 concentrations would provide valuable clinical information to assess disease severity in silicosis., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Recent data show that arsenic may play a role in obesity-related diseases. However, urinary arsenic studies report an inverse association between arsenic level and body mass index (BMI). We explored whether toenail arsenic, a long-term exposure measure, was associated with BMI in 74 welders with known arsenic exposure. BMI showed significant inverse associations with toenail arsenic (p=0.01), which persisted in models adjusted for demographics, diet and work history. It is unclear whether low arsenic biomarker concentrations in high BMI subjects truly reflect lower exposures, or instead reflect internal or metabolic changes that alter arsenic metabolism and tissue deposition., (Copyright © 2014 Elsevier Inc. All rights reserved.)

PR toxin, a mycotoxin from cultures of Penicillium roqueforti, inhibited the in vitro activities of rat liver DNA polymerase alpha, beta, and gamma irrespectively of the nature of template-primer used. The concentration required for 50% inhibition of DNA polymerase alpha was 5-6 X 10(-6) M, while those for DNA polymerase beta and gamma were several times higher. By using DNA polymerase beta as a model, and based on the enzyme and template-primer concentration effects and also from the kinetic analysis on PR toxin inhibition, we concluded that two action mechanisms of PR toxin inhibition on in vitro DNA synthesis are operative. Inhibition of the in vitro DNA synthesis directed by DNA template was mediated primarily through alteration of the enzyme itself, whereas in the DNA synthesis reaction directed by RNA template DNA primer, the impairment of template or primer function due to PR toxin treatment probably had occurred. The inhibition of DNA polymerase by PR toxin persisted even after exhaustive dialysis. Addition of PR toxin to an ongoing reaction also inhibited DNA synthesis. Inactivation of DNA polymerase activity of PR toxin likely involved some essential amino acid residues other than sulfhydryl groups.

The effect of dietary selenite on the binding characteristics of serum proteins was investigated with rats. In the control serum, the maximal binding of phenylmercuric acetate (PMA) and methylmercuric chloride (MMC) to rat serum protein was approx. 18 and 9 nmoles per mg protein, respectively. The binding of Hg2+ was biphasic and it did not reach a maximum at the concentrations used. Selenite treatment caused a reduction in binding capacity of serum proteins to Hg2+ and PMA, and an increase in the binding affinities. However, there were no such changes for the binding of MMC. Selenite protection from mercury toxicity, therefore, acts not only via a change in tissue distribution and a change in the formation of seleno-proteins but, also, via a change in the binding characteristics to some mercury compounds. In the case of methylmercury, a different mechanism of protection must exist as the modification of tissue distribution, its binding to subcellular and soluble proteins and the binding characteristics remained equivocal.