Prediagnostic whole blood cadmium and molybdenum associated with pancreatic cancer in an American cohort.

Environmental exposures such as cadmium might be contributing to the increasing incidence of pancreatic cancer. Few prospective studies have examined the association between trace elements and pancreatic ductal adenocarcinoma (PDAC). We conducted a nested case-control study in participants aged 55-74 years at baseline from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort to examine the association between 12 trace elements measured in predignostic whole blood and PDAC. From May 1998 through December 2014, 318 incident PDAC cases were identified during follow-up to 16.7 years. Two controls (n = 636) alive when each case was diagnosed were selected and matched by age (+ 5 years), sex, calendar date of blood draw (2-month blocks), and race and ethnic group. We used multivariable adjusted conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Cadmium and molybdenum were associated with PDAC [highest compared to lowest quintile: cadmium OR=1.81; 95% CI: 01.12, 2.95; P-trend = 0.03; molybdenum OR=0.50; 95% CI: 0.32, 0.80; P-trend = 0.02]. The inverse molybdenum association was only observed among ever smokers (OR=0.31, 95% CI: 0.17, 0.58, P-trend= 0.003, P-interaction=0.03) with no association in never smokers. Lead, arsenic, and other trace elements were not associated with PDAC. Our results support that increasing prediagnostic whole blood cadmium increases while molybdenum reduces PDAC risk.

Serum zinc concentration and dietary zinc intake in relation to cognitive function: an analysis of the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

PURPOSE: There are several pathways by which zinc may be a modifiable factor to slow age-related cognitive decline. We investigated the associations between serum and dietary zinc and cognitive impairment in a longitudinal cohort. METHODS: We used data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort (n = 30,239) and the REGARDS Trace Element Study (n = 2666). Baseline serum zinc concentrations (2003-2007) were measured using inductively coupled plasma mass spectrometry. Baseline dietary zinc intake was measured via the Block food frequency questionnaire. Serum zinc concentrations and dietary zinc intake were categorized into quartiles. The outcome of interest was impairment on the Six-Item Screener (SIS), a measure of global cognitive functioning administered annually. The Enhanced Cognitive Battery (ECB), a more comprehensive series of tests assessing memory and fluency, was administered every two years and considered a secondary outcome. Associations between zinc and incident impairment were assessed using multivariable logistic regression. RESULTS: Among 2065 participants with serum zinc data, 184 individuals developed impairment over 10 years of follow-up. In adjusted models, there was no significant association between serum zinc and impairment as assessed by the SIS or the ECB. Among 18,103 participants who had dietary data, 1424 experienced incident impairment on the SIS. Dietary zinc intake was not significantly associated with impairment as assessed by the SIS or the ECB in adjusted models. CONCLUSION: Findings from this U.S. cohort did not support the hypothesis that serum zinc concentration or dietary zinc intake is associated with the risk of cognitive impairment.

Regulation of SELENOF translation by eIF4a3: Possible role in prostate cancer progression.

The levels of the SELENOF selenoprotein are dramatically reduced in prostate cancer compared to adjacent benign tissue and reducing SELENOF in prostate epithelial cells results in the acquisition of features of the transformed phenotype. It was hypothesized that the aberrant increase in the eiF4a3 translation factor, which has an established role in RNA splicing and the regulation of selenoprotein translation, contributes to the lower levels of SELENOF. Using the available databases, eIF4a3 messenger RNA (mRNA) levels are elevated in prostate cancer compared to normal tissue as is the hypomethylation of the corresponding gene. Using a prostate cancer tissue microarray, we established that eiF4a3 levels are higher in prostate cancer tissue. Ectopic expression of eIF4a3 in prostate cancer cells reduced SELENOF levels and attenuated the readthrough of the UGA codon using a specialized reporter construct designed to examine UGA decoding, with the opposite effects observed using eIF4a3 knock-down constructs. Direct binding of eIF4a3 to the regulatory regions of SELENOF mRNA was established with pull-down experiments. Lastly, we show that an eIF4a3 inhibitor, eIF4a3-IN-2, increases SELENOF levels, UGA readthrough, and reduces binding of eIF4a3 to the SELENOF mRNA 3'-UTR in exposed cells. These data establish eIF4a3 as a likely prostate cancer oncogene and a regulator of SELENOF translation.

Development and Characterization of a AuNP-Genipin-Viscoelastic Collagen Material.

Lower back pain is one of the leading causes of disability, affecting 11.9% of the population worldwide and studies have shown that intervertebral disc degeneration is a common cause for chronic lower back pain. We have explored the combination of three components, viscoelastic collagen, genipin, and gold nanoparticles to determine its potential to promote regeneration of the intervertebral disc, specifically for nucleus pulposus regeneration. The goal of this study was to develop, fabricate and characterize different formulations of viscoelastic collagen conjugated with gold nanoparticles and genipin to assess the feasibility as a tissue template. Results demonstrated the successful attachment of gold nanoparticles to the viscoelastic collagen utilizing the genipin crosslinker. For each of the viscoelastic collagen compositions examined, cell biocompatibility was achieved. The results also demonstrated an increase in stiffness of the material with different sizes and concentrations of AuNPs. Results from the TEM and STEM also demonstrated that the viscoelastic collagen that was developed did not display the characteristic D banding pattern of polymerized collagen. The findings from this study could lead to the development of a more efficient and cost-effective treatment for patients with chronic back pain caused by IVD degeneration.

Polymeric Interlayer Strengthening with Boron Neutron Capture Radiation Treatment for Laminated Glass.

Polymer interlayer materials are utilized in laminated glass systems to provide increased resilience from blast incidents. The polymer chains within the interlayer material can benefit from material modifications that increase the crosslinking between adjacent chains. One theorized method of targeted crosslinking is made possible through a boron neutron capture process. This process utilizes neutron radiation that bombards boron material, thus producing emissions of highly energetic particles into the polymer. The method has been experimentally utilized for bulk material processing as well as surface treatment. The surface treatment process has been extensively investigated in this study to manipulate polymers commonly used as interlayer material. Comparison evaluation tests have been completed to show the material behavior change through static tensile loading, dynamic tensile loading, indentation testing, and scratch resistance testing. Results present the specific material behavior changes, effects on different interlayer material, and optimizations for the treatment processes. Data resulting from these tests will expand the understanding of the material behavior changes from treatment techniques and show evidence of the expected crosslinking. This understanding will lead to a quantifiable application of system capacities to improve the future designs of the window and building systems and lead to a safer, more secure, and resilient infrastructure. Polymer treatment by boron neutron capture radiation has produced polymer interlayers with the potential of increased resilience to blast. The research to date has evaluated treated polymers and shown that the hardening and increased elasticity of the material can be initiated through treatment, thus indicating crosslinking behavior. These results show distinct changes in the material behavior, particularly with the EVA interlayer material. The harder surface of the interlayer may resist the cutting of the interlayer surface by glass shards. Scratch resistance was 30% higher and the measured hardness was 100% on treated surfaces. Treated EVA exhibited a 40% higher stress capacity, a 35% higher toughness, and a 40% increase in the elasticity of the material. The overall toughness increase of the treated polymer material allows for a higher energy absorption, and an overall improvement of window performance in blast conditions. The treatment technique can be applied to a variety of window interlayer products for optimal material performance in blast conditions.

Mercury, selenium, and fatty acids in the axial muscle of largemouth bass: evaluating the influence of seasonal and sexual changes in fish condition and reproductive status.

Largemouth bass (LMB, 265-475 mm) were collected to document whether changes in fish condition and reproductive status influenced the concentration of total mercury (Hg) and selenium (Se) in axial muscle by season and sex. The fatty acid (FA) composition of fish was also examined to describe seasonal and sexual differences and identify whether arachidonic acid (ARA) could be used as a biomarker of Hg toxicity. There was a trend for females to have lower (p < 0.062) Se concentrations than males. The concentration of Se for females during spring (mean ± SD, 686 ± 51 ng/g dw) was 15% lower than males (806 ± 67 ng/g dw). Lower Se concentrations in females than males continued through summer and fall. Concentration of Hg for females during spring (152 ± 39 ng/g ww) was also 59% lower than males (373 ± 303 ng/g ww), but the difference was not significant (p > 0.2). The percent of lipids was greatest in fall and winter (3%) and comprised primarily of omega-3 fatty acids (35 g/100 g lipid). Fish condition as measured by percent lipids and relative weight was negatively (p < 0.02) related to Hg concentration for females and males. Lipid content for both sexes was also positively (p < 0.05) related to the Se:Hg ratio. Relative weight was positively related to the Se:Hg ratio for females during all seasons (p = 0.014), but only during spring and summer for males (p < 0.007). A low Se:Hg value was associated with an elevation in ARA for both sexes and a reduced hepatosomatic index in males. Data suggested that females transferred muscle stores of Se and Hg to developing oocytes during spring. This study generates hypotheses regarding the physiological drivers of seasonal and sexual variability in Hg, Se, and FA in LMB that may be applicable to other species and have implications for fisheries health and management.

Magnesium intake is inversely associated with risk of non-alcoholic fatty liver disease among American adults.

PURPOSE: Human data are limited linking magnesium (Mg) intake to the risk of non-alcoholic fatty liver disease (NAFLD). We aimed to examine the association between Mg intake and the risk of NAFLD among young adults in the US with a 25-year follow-up. METHODS: This study included 2685 participants from the Coronary Artery Risk Development in Young Adult (CARDIA) study. Diet and dietary supplements were assessed at baseline (1985-1986) and exam years 7 and 20 using an interview-based dietary history. NAFLD, defined as liver attenuation ≤ 51 Hounsfield Units excluding secondary causes of liver fat accumulation, was identified by non-contrast-computed tomography scanning at exam year 25. Multivariable-adjusted logistic regression model was used to examine the associations between cumulative average total intake of Mg (dietary plus supplemental) and NAFLD odds. RESULTS: A total of 629 NAFLD cases were documented. After adjustment for potential confounders, an inverse association between total Mg intake and NAFLD odds was observed. Compared to participants in the lowest quintile of total Mg intake, the odds of NAFLD was 55% lower among individuals in the highest quintile [multivariable-adjusted odds ratio (OR) = 0.45, 95% confidence interval (CI) (0.23, 0.85), p for trend = 0.03]. Consistently, whole-grain consumption, a major dietary source of Mg, was inversely associated with NAFLD odds (p for trend = 0.02). CONCLUSIONS: This study suggests that higher cumulative intake of Mg throughout adulthood is associated with lower odds of NAFLD in midlife. Future studies are needed to establish a possible causal relationship.

Radium dial workers: back to the future.

PURPOSE: This paper reviews the history of the radium dial workers in the United States, summarizes the scientific progress made since the last evaluation in the early 1990s, and discusses current progress in updating the epidemiologic cohort and applying new dosimetric models for radiation risk assessment. BACKGROUND: The discoveries of radiation and radioactivity led quickly to medical and commercial applications at the turn of the 20th century, including the development of radioluminescent paint, made by combining radium with phosphorescent material and adhesive. Workers involved with the painting of dials and instruments included painters, handlers, ancillary workers, and chemists who fabricated the paint. Dial painters were primarily women and, prior to the mid to late 1920s, would use their lips to give the brush a fine point, resulting in high intakes of radium. The tragic experience of the dial painters had a significant impact on industrial safety standards, including protection measures taken during the Manhattan Project. The dial workers study has formed the basis for radiation protection standards for intakes of radionuclides by workers and the public. EPIDEMIOLOGIC APPROACH: The mortality experience of 3,276 radium dial painters and handlers employed between 1913 and 1949 is being determined through 2019. The last epidemiologic follow-up was 30 years ago when most of these workers were still alive. Nearly 65% were born before 1920, 37.5% were teenagers when first hired, and nearly 50% were hired before 1930 when the habit of placing brushes in mouths essentially stopped. Comprehensive dose reconstruction techniques are being applied to estimate organ doses for each worker related to the intake of 226Ra, 228Ra, and associated photon exposures. Time dependent dose-response analyses will estimate lifetime risks for specific causes of death. DISCUSSION: The study of radium dial workers is part of the Million Person Study of low-dose health effects that is designed to evaluate radiation risks among healthy American workers and veterans. Despite being one of the most important and influential radiation effects studies ever conducted, shifting programmatic responsibilities and declining funding led to the termination of the radium program of studies in the early 1990s. Renewed interest and opportunity have arisen. With scientific progress made in dosimetric methodology and models, the ability to perform a study over the entire life span, and the potential applicability to other scenarios such as medicine, environmental contamination and space exploration, the radium dial workers have once again come to the forefront.

The use of gold nanoparticles in improving ACL graft performance in an ovine model.

Surgical repair of the anterior cruciate ligament (ACL) can involve autograft or allograft materials. Allografts are typically chosen to avoid donor site morbidity associated with autografts harvest, but they can also result in a prolonged inflammatory period and delayed graft remodeling when compared to autografts. The aim of this study was to investigate the use of gold nanoparticles (AuNPs) conjugated to allografts to determine if AuNPs can reduce inflammation and enhance graft remodeling in an ovine model. Six sheep had their ACL surgically removed and replaced with a decellularized human gracilis tendon. Three of the sheep received grafts conjugated with 20 nm gold nanoparticles, while three of the sheep received grafts without the gold nanoparticles. The sheep were sacrificed 8 weeks after ACL reconstruction. Immediately following sacrifice, joint fluid was collected for cytology. Semi-quantitative histological scoring of the bone tunnel portion and the intra-articular portion of the grafts were performed independently along with descriptive analysis of histologic changes and quantitative analysis of revascularization. The results demonstrated that AuNP experimental grafts had an overall better histological scores than the non-AuNPs graft. The AuNPs grafts exhibited decreased inflammation in the bone tunnel portion of the graft, the intra-articular portion of the graft, and in the synovial fluid cell count. Overall, the results demonstrated that the grafts conjugated with nanoparticles have the potential to be influence inflammation and overall remodeling response.

Serum Zinc Levels and Incidence of Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

BACKGROUND AND PURPOSE: Despite zinc's role as an antioxidant and anti-inflammatory agent, prospective studies relating zinc levels to ischemic stroke risk are lacking. To examine the association between serum zinc levels and incidence of ischemic stroke in a US population. METHODS: Using a case-cohort study nested within the Reasons for Geographic and Racial Differences in Stroke cohort, participants were randomly selected from the Reasons for Geographic and Racial Differences in Stroke cohort to generate a sub-cohort (n=2346). All incident ischemic stroke cases as of September 2012 (n=660) were included, with 62 incident cases overlapping in the sub-cohort. Serum zinc levels were measured at baseline. Barlow-weighted Cox's proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios and the corresponding 95% CI of ischemic stroke by serum zinc levels. RESULTS: The median zinc level for the sub-cohort was 121.19 µg/dL (interquartile range, 104.86-140.39 µg/dL). Serum zinc levels were inversely associated with incidence of ischemic stroke after adjustment for potential confounders (quartile 4 versus quartile 1: hazard ratio, 0.78 [95% CI, 0.61-0.98], P=0.03 for trend). When stratified by prespecified factors (sex, race, region), only sex showed a significant modification (P=0.03 for interaction). The inverse association was more pronounced among females (quartile 4 versus quartile 1: hazard ratio, 0.58 [95% CI, 0.41-0.84], P<0.01 for trend) than males (quartile 4 versus quartile 1: hazard ratio, 1.08 [95% CI, 0.78-1.51], P=0.92 for trend). CONCLUSIONS: Serum zinc concentration was inversely associated with incidence of ischemic stroke, especially among women, indicating that low zinc levels may be a risk factor for ischemic stroke.

Low- and moderate- levels of arsenic exposure in young adulthood and incidence of chronic kidney disease: Findings from the CARDIA Trace Element Study.

BACKGROUND: It is unclear whether arsenic exerts adverse health effects on the kidney at low- and moderate- levels of exposure. We prospectively examined toenail arsenic concentrations measured during young adulthood in relation to incidence of chronic kidney disease (CKD) in midlife. METHODS: A total of 3768 participants (53 % female and 48 % blacks) in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included. Arsenic concentration in toenail clippings was assessed by using inductively coupled plasma mass spectrometry at CARDIA exam year 2. Incident CKD was identified if having estimated glomerular filtration rate <60 mL/min per 1.73 m² or albuminuria >30 mg/g. The association between toenail arsenic levels and CKD incidence over a mean of 24 years of follow-up was examined using multivariable-adjusted Cox proportional hazards models. RESULTS: After controlling for potential confounders, including demographics, socioeconomics, lifestyle factors, clinical measurements of blood pressure, lipids, and glucose, and medical history, arsenic exposure measured in toenails was not associated with CKD incidence (quintile 5 versus quintile 1: hazard ratio = 1.04, 95 % confidence interval = 0.78-1.40, P for trend = 0.38). CONCLUSION: This longitudinal study does not support the hypothesis that low- and moderate- levels of arsenic exposure are associated with elevated incidence of CKD in the US general population. Further studies are need to investigate species of arsenic biomarkers in relation to nephrotoxicity.

Brain Bromine Levels Associated with Alzheimer's Disease Neuropathology.

BACKGROUND: Bromine is a naturally occurring element that is widely present in the human environment in various chemical forms primarily as flame retardants, pesticides, and water treatments. OBJECTIVE: In this exploratory study, we investigated the association of brain bromine concentrations on Alzheimer's disease (AD) neuropathology, cerebral infarcts, and Lewy bodies. METHODS: The study was conducted in 215 deceased participants of the Memory and Aging Project, a clinical-pathologic cohort study. Brain bromine levels were measured using instrumental neutron activation analysis. Multiple brain regions were assessed for diffuse and neuritic plaques, neurofibrillary tangles, cerebral macro-and microinfarcts, and Lewy bodies. Standardized measures of AD pathology (Braak, CERAD, NIA-Reagan, global AD pathology) were computed. RESULTS: In linear regression models, the higher brain bromine levels were associated with more AD neuropathology (Braak (p trend = 0.01); CERAD (p trend = 0.02); NIA-Reagan (p trend = 0.02). CONCLUSION: Bromine accumulation in the brain is associated with higher level of AD neuropathology. The potential deleterious effects of this element on AD need further exploration.

Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology.

Cortical iron has been shown to be elevated in Alzheimer's disease (AD), but the impact of the directly measured iron on the clinical syndrome has not been assessed. We investigated the association between post-mortem iron levels with the clinical and pathological diagnosis of AD, its severity, and the rate of cognitive decline in the 12 years prior to death in subjects from the Memory and Aging Project (n = 209). Iron was elevated (ß [SE] = 9.7 [2.6]; P = 3.0 × 10-4) in the inferior temporal cortex only in subjects who were diagnosed with clinical AD during life and had a diagnosis of AD confirmed post-mortem by standardized criteria. Although iron was weakly associated with the extent of proteinopathy in tissue with AD neuropathology, it was strongly associated with the rate of cognitive decline (e.g., global cognition: ß [SE] = -0.040 [0.005], P = 1.6 × 10-14). Thus, cortical iron might act to propel cognitive deterioration upon the underlying proteinopathy of AD, possibly by inducing oxidative stress or ferroptotic cell death, or may be related to an inflammatory response.

Characterization of the neutron flux during production of 18F at a medical cyclotron and evaluation of the incidental neutron spectrum for neutron damage studies.

The fast neutron spectrum was measured in an irradiation position adjacent to two 18F (fluorine-18) production targets at a medical cyclotron. The neutron spectrum was modeled using MCNP6 and experimentally determined using activation foils. A three-group neutron spectrum was determined using an over-determined least squares fitting method. The MCNP6 model results and measurements of the activation foils were used as input to unfold the neutron spectrum using the STAYSL PNNL code. The neutron spectrum adjacent to the 18F production target was evaluated for use in incidental experiments to evaluate neutron-induced radiolysis of polyurethane and radiation hardness testing of electronics. The fast neutron flux near the 18F target between the energies of 0.4 - 16.5 MeV was 1.8 - 3.0x109 n cm-2s-1. The neutron dose rate in polyurethane at the irradiation position was 2.8 cGy s-1- 5.8 cGys-1. The 1 MeV equivalent neutron flux was 2.4x109 n cm-2s-1 - 4.0x109 n cm-2s-1.

Methylmercury exposure, genetic variation in metabolic enzymes, and the risk of glioma.

Methylmercury (MeHg) is an environmental neurotoxin with human exposure mainly from dietary intake of contaminated fish. Exposure to MeHg has been implicated in neurological damage, but research on its role in cancers, specifically glioma, is limited. In a glioma case-control study, we examined associations between toenail mercury (Hg) and glioma risk. We also examined genetic polymorphisms in 13 genes related to MeHg metabolism for association with glioma risk; genetic associations were also studied in the UK Biobank cohort. Median toenail Hg in cases and controls, respectively, was 0.066 µg/g and 0.069 µg/g (interquartile range (IQR): 0.032-0.161 and 0.031-0.150 µg/g). Toenail Hg was not found to be significantly associated with glioma risk (Odds Ratio: 1.02; 95% Confidence Interval: 0.91, 1.14; p = 0.70 in analysis for ordinal trend with increasing quartile of toenail MeHg). No genetic variant was statistically significant in both of the studies; one variant, rs11859163 (MMP2) had a combined p-value of 0.02 though it was no longer significant after adjustment for multiple testing (Bonferroni corrected p = 1). This study does not support the hypothesis that exposure to MeHg plays a role in the development of glioma at levels of exposure found in this study population.

Electrospun PCL, gold nanoparticles, and soy lecithin composite material for tissue engineering applications.

Soy lecithin has been shown to play a critical role in cell signaling and cellular membrane structure. In addition, it has been shown to increase biocompatibility, hydrophilicity, and decrease cytotoxicity. Gold nanoparticles have also shown to improve cellularity. Lecithin, gold nanoparticles, and polycaprolactone (PCL) solutions were electrospun in order to develop unique mesh materials for the treatment of osteoarthritis. The electrospinning parameters were optimized to achieve different solution ratios for fiber optimization. The amount of lecithin mixed with PCL varied from 30 wt.% to 50 wt.% . Gold nanoparticles (1% to 10% concentrations) were also added to lecithin-PCL mixture. The mechanical and chemical properties of the fiber mesh were analyzed via contact angle test, tensile mechanical tests, Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Cell viability was measured using a WST-1 Assay. Scanning electron microscopy confirmed the successful formation of fiber mesh. The compositions of 40% soy lecithin with PCL in 40% solvent (40:40) resulted in the most well-formed fiber mesh. DSC melt temperatures were statically insignificant; uniaxial stresses and the moduli resulted in no significant difference between the test composition and pristine PCL compositions. WST-1 assay revealed all compositions were non-cytotoxic. Overall, the addition of lecithin increased hydrophilicity while maintaining cell viability and the mechanical and chemical properties of PCL. This study demonstrated that it is possible to successfully electrospin a lecithin, gold nanoparticle, and polycaprolactone scaffold for tissue engineering applications.

Analysis and imaging of boron distribution in maize by quantitative neutron capture radiography.

Quantitative neutron capture radiography (QNCR) of 10B found in pre-dried maize samples has been conducted. Calibration standards constructed from filter paper mimicked plant tissues to reduce confounding matrix effects. A mathematical track elimination method improves the LOD as well as the visual contrast image at low boron concentration levels. The LOD for total boron is 1.7 µg/g in a 4 mm2 region of interest (ROI). The w(B) in five individual maize tassel meristems has been determined to be 14.9 µg/g - 21.2 µg/g.

Urinary cadmium concentration and the risk of ischemic stroke.

OBJECTIVES: To examine the association between urinary cadmium levels and the incidence of ischemic stroke and to explore possible effect modifications. METHODS: A case-cohort study was designed nested in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including 680 adjudicated incident cases of ischemic stroke and 2,540 participants in a randomly selected subcohort. Urinary creatinine-corrected cadmium concentration was measured at baseline. Multivariable-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated with the Barlow weighting method for the Cox proportional hazards regression model. RESULTS: The median urinary cadmium concentration was 0.42 (interquartile range 0.27-0.68) µg/g creatinine. After adjustment for potential confounders, urinary cadmium was associated with increased incidence of ischemic stroke (quintile 5 vs quintile 1: HR 1.50, 95% CI 1.01-2.22, p for trend = 0.02). The observed association was more pronounced among participants in the lowest serum zinc tertile (tertile 3 vs tertile 1: HR 1.82, 95% CI 1.06-3.11, p for trend = 0.004, p for interaction = 0.05) but was attenuated and became nonsignificant among never smokers (tertile 3 vs tertile 1: never smokers: HR 1.27, 95% CI 0.80-2.03, p for trend = 0.29; ever smokers: HR 1.60, 95% CI 1.06-2.43, p for trend = 0.07, p for interaction = 0.51). CONCLUSIONS: Findings from this study suggest that cadmium exposure may be an independent risk factor for ischemic stroke in the US general population. Never smoking and maintaining a high serum zinc level may ameliorate the potential adverse effects of cadmium exposure.

Toenail selenium, genetic variation in selenoenzymes and risk and outcome in glioma.

BACKGROUND: Selenium is an essential trace element obtained through diet that plays a critical role in DNA synthesis and protection from oxidative damage. Selenium intake and polymorphisms in selenoproteins have been linked to the risk of certain cancers though data for glioma are sparse. METHODS: In a case-control study of glioma, we examined the associations of selenium in toenails and genetic variants in the selenoenzyme pathway with the risk of glioma and patient survival. A total of 423 genetic variants in 29 candidate genes in the selenoenzyme pathway were studied in 1547 glioma cases and 1014 healthy controls. Genetic associations were also examined in the UK Biobank cohort comprised of 313,868 persons with 322 incident glioma cases. Toenail selenium was measured in a subcohort of 300 glioma cases and 300 age-matched controls from the case-control study. RESULTS: None of the 423 variants studied were consistently associated with glioma risk in the case-control and cohort studies. Moreover, toenail selenium in the case-control study had no significant association with glioma risk (p trend = 0.70) or patient survival among 254 patients with high grade tumors (p trend = 0.70). CONCLUSION: The present study offers no support for the hypothesis that selenium plays a role in the onset of glioma or patient outcome.

Serum mercury concentration and the risk of ischemic stroke: The REasons for Geographic and Racial Differences in Stroke Trace Element Study.

BACKGROUND: Although biologically plausible, epidemiological evidence linking exposure to methylmercury with increased risk of ischemic stroke is limited. The effects of methylmercury may be modified by selenium, which is an anti-oxidant that often co-exists with mercury in fish. OBJECTIVES: To examine the association between serum mercury levels with the incidence of ischemic stroke and to explore the possible effect modifications by serum selenium levels and demographic and geographic factors. METHODS: A case-cohort study was designed nested in the REasons for Geographic and Racial Differences in Stroke cohort, including 662 adjudicated incident cases of ischemic stroke and 2494 participants in a randomly selected sub-cohort. Serum mercury was measured using samples collected at recruitment. Multivariable-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated using the Barlow-weighting method for the Cox proportional hazards regression model. RESULTS: No statistically significant association was observed between serum mercury concentration and the incidence of ischemic stroke (the highest vs. lowest quintile of mercury levels: HR = 0.82; 95% CI = 0.55-1.22; P for linear trend = 0.42). Sex (P for interaction = 0.06), but not serum selenium levels, modified the association; a more evident trend toward lower incidence of ischemic stroke with higher mercury levels was observed among women. CONCLUSION: This study does not support an association between mercury and the incidence of ischemic stroke within a population with low-to-moderate level of exposure. Further studies are needed to explore the possibility of mercury-induced ischemic stroke toxicity in other populations at higher exposure levels.