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.

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.

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.

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.

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.

Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

BACKGROUND AND PURPOSE: The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States. METHODS: We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species. RESULTS: The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident. CONCLUSIONS: A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research.

Cross sectional study of serum selenium concentration and esophageal squamous dysplasia in western Kenya.

BACKGROUND: Low serum selenium status has been associated with increased risk of esophageal squamous cell carcinoma (ESCC). East Africa is a region of high ESCC incidence and is known to have low soil selenium levels, but this association has not previously been evaluated. In this study we assessed the association of serum selenium concentration and the prevalence of esophageal squamous dysplasia (ESD), the precursor lesion of ESCC, in a cross-sectional study of subjects from Bomet, Kenya. METHODS: 294 asymptomatic adult residents of Bomet, Kenya completed questionnaires and underwent endoscopy with Lugol's iodine staining and biopsy for detection of ESD. Serum selenium concentrations were measured by instrumental neutron activation analysis. Odds ratios (OR) and confidence intervals (95% CI) for associations between serum selenium and ESD were calculated using unconditional logistic regression. RESULTS: The mean serum selenium concentration was 85.5 (±28.3) µg/L. Forty-two ESD cases were identified (14% of those screened), including 5 (12%) in selenium quartile 1 (Q1), 5 (12%) in Q2, 15 (36%) in Q3, and 17 (40%) in Q4. Higher serum selenium was associated with prevalence of ESD (Q4 vs Q1: OR: 3.03; 95% CI: 1.05-8.74) and this association remained after adjusting for potential confounders (Q4 vs Q1: OR: 3.87; 95% CI: 1.06-14.19). CONCLUSION: This is the first study to evaluate the association of serum selenium concentration and esophageal squamous dysplasia in an African population at high risk for ESCC. We found a positive association between higher serum selenium concentration and prevalence of ESD, an association contrary to our original hypothesis. Further work is needed to better understand the role of selenium in the etiology of ESCC in this region, and to develop effective ESCC prevention and control strategies.

Measurement of Uranium Isotope Ratios in Keratinous Materials: A Noninvasive Bioassay for Special Nuclear Material.

Hair, toenail, and fingernail are noninvasive, integrative biological monitors routinely used to assess mineral intake.1-4 In this study, we demonstrate the feasibility of distinguishing between exposure to natural, depleted, and enriched U by measuring the (235)U/(238)U, (234)U/(238)U, and (236)U/(238)U ratios in the hair, fingernails, and toenails of occupationally exposed workers and control volunteers. The exposure history of cases and controls to non-natural U was assessed through voluntary self-reporting using a simple questionnaire. The measured U isotope ratios and U concentration in the hair, toenail, and fingernail of cases were compared to a nonexposed control group. No difference was observed in the uranium concentration between the two groups. Significant differences between the cases and the control group were observed in the (235)U/(238)U and (236)U/(238)U isotope ratios but not the (234)U/(238)U. This is the first time that hair, fingernail, and toenail have been demonstrated to be sensitive to occupational exposure to enriched and depleted U, a result with significant implications for proliferation compliance monitoring.

Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes.

The application of boron neutron capture therapy (BNCT) following liposomal delivery of a (10)B-enriched polyhedral borane and a carborane against mouse mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with a mean diameter of 134 nm or less, composed of an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating Na3[1-(2'-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer, were injected into the tail veins of female BALB/c mice bearing right flank EMT6 tumors. Biodistribution studies indicated that two identical injections given 24 h apart resulted in tumor boron levels exceeding 67 µg/g tumor at 54 h--with tumor/blood boron ratios being greatest at 96 h (5.68:1; 43 µg boron/g tumor)--following the initial injection. For BNCT experiments, tumor-bearing mice were irradiated 54 h after the initial injection for 30 min with thermal neutrons, resulting in a total fluence of 1.6 × 10(12) neutrons per cm(2) (±7%). Significant suppression of tumor growth was observed in mice given BNCT vs. control mice (only 424% increase in tumor volume at 14 d post irradiation vs. 1551% in untreated controls). In a separate experiment in which mice were given a second injection/irradiation treatment 7 d after the first, the tumor growth was vastly diminished (186% tumor volume increase at 14 d). A similar response was obtained for mice irradiated for 60 min (169% increase at 14 d), suggesting that neutron fluence was the limiting factor controlling BNCT efficacy in this study.

Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults.

IMPORTANCE: Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern. OBJECTIVE: To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumption or brain mercury levels are correlated with brain neuropathologies. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analyses of deceased participants in the Memory and Aging Project clinical neuropathological cohort study, 2004-2013. Participants resided in Chicago retirement communities and subsidized housing. The study included 286 autopsied brains of 554 deceased participants (51.6%). The mean (SD) age at death was 89.9 (6.1) years, 67% (193) were women, and the mean (SD) educational attainment was 14.6 (2.7) years. EXPOSURES: Seafood intake was first measured by a food frequency questionnaire at a mean of 4.5 years before death. MAIN OUTCOMES AND MEASURES: Dementia-related pathologies assessed were Alzheimer disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. Dietary consumption of seafood and n-3 fatty acids was annually assessed by a food frequency questionnaire in the years before death. Tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses. RESULTS: Among the 286 autopsied brains of 544 participants, brain mercury levels were positively correlated with the number of seafood meals consumed per week (ρ = 0.16; P = .02). In models adjusted for age, sex, education, and total energy intake, seafood consumption (≥ 1 meal[s]/week) was significantly correlated with less Alzheimer disease pathology including lower density of neuritic plaques (ß = -0.69 score units [95% CI, -1.34 to -0.04]), less severe and widespread neurofibrillary tangles (ß = -0.77 score units [95% CI, -1.52 to -0.02]), and lower neuropathologically defined Alzheimer disease (ß = -0.53 score units [95% CI, -0.96 to -0.10]) but only among apolipoprotein E (APOE ε4) carriers. Higher intake levels of α-linolenic acid (18:3 n-3) were correlated with lower odds of cerebral macroinfarctions (odds ratio for tertiles 3 vs 1, 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation had no statistically significant correlation with any neuropathologic marker. Higher brain concentrations of mercury were not significantly correlated with increased levels of brain neuropathology. CONCLUSIONS AND RELEVANCE: In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology.

Prostate MRI: a national survey of Urologist's attitudes and perceptions.

INTRODUCTION: The use of multi-parametric (MP) MRI to diagnose prostate cancer has been the subject of intense research, with many studies showing positive results. The purpose of our study is to better understand the accessibility, role, and perceived accuracy of MP-MRI in practice by surveying practicing urologists. MATERIALS AND METHODS: Surveys were sent to 7,400 practicing American Urological Association member physicians with a current email address. The survey asked demographic information and addressed access, accuracy, cost, and role of prostate MRI in clinical practice. RESULTS: Our survey elicited 276 responses. Respondents felt that limited access and prohibitive cost of MP-MRI limits its use, 72% and 59% respectively. Academic urologists ordered more MP-MRI studies per year than those in private practice (43.3% vs. 21.1%; p<0.001). Urologists who performed more than 30 prostatectomies a year were more likely to feel that an MP-MRI would change their surgical approach (37.5% vs. 19.6%, p-value=0.002). Only 25% of respondents agreed or strongly agreed that MP-MRI should be used in active surveillance. For patients with negative biopsies and elevated PSA, 39% reported MP-MRI to be very useful. CONCLUSIONS: Our study found that MP-MRI use is most prominent among practitioners who are oncology fellowship-trained, practice at academic centers, and perform more than 30 prostatectomies per year. Limited access and prohibitive cost of MP-MRI may limit its utility in practice. Additionally, study participants perceive a lack of accuracy of MP-MRI, which is contrary to the recent literature.

Hemorrhagic Cystitis Requiring Bladder Irrigation is Associated with Poor Mortality in Hospitalized Stem Cell Transplant Patients.

PURPOSE: To evaluate the overall prognosis of post-stem cell transplant inpatients who required continuous bladder irrigation (CBI) for hematuria. MATERIALS AND METHODS: We performed a retrospective analysis of adult stem cell transplant recipients who received CBI for de novo hemorrhagic cystitis as inpatients on the bone marrow transplant service at Washington University from 2011-2013. Patients who had a history of genitourinary malignancy and/or recent surgical urologic intervention were excluded. Multiple variables were examined for association with death. RESULTS: Thirty-three patients met our inclusion criteria, with a mean age of 48 years (23-65). Common malignancies included acute myelogenous leukemia (17/33, 57%), acute lymphocytic leukemia (3/33, 10%), and peripheral T cell lymphoma (3/33, 10%). Median time from stem cell transplant to need for CBI was 2.5 months (0 days-6.6 years). All patients had previously undergone chemotherapy (33/33, 100%) and 14 had undergone prior radiation therapy (14/33, 42%). Twenty-eight patients had an infectious disease (28/33, 85%), most commonly BK viremia (19/33, 58%), cytomegalovirus viremia (17/33, 51%), and bacterial urinary tract infection (8/33, 24%). Twenty-two patients expired during the same admission as CBI treatment (22/33 or 67% of total patients, 22/28 or 79% of deaths), with a 30-day mortality of 52% and a 90-day mortality of 73% from the start of CBI. CONCLUSIONS: Hemorrhagic cystitis requiring CBI is a symptom of severe systemic disease in stem cell transplant patients. The need for CBI administration may be a marker for mortality risk from a variety of systemic insults, rather than directly attributable to the hematuria.

Toenail iron, genetic determinants of iron status, and the risk of glioma.

PURPOSE: Iron is essential for oxygen transport and oxidative metabolism; however, elevated iron stores can trigger overproduction of reactive oxygen species and induce DNA damage. Little is known about the association between body iron stores and glioma risk. This study examined the associations of iron levels measured in toenails and genetic variants linked to body iron stores with risk of glioma in a clinic-based case-control study. METHODS: Samples were collected a median of 24 days following glioma diagnosis in the cases (10th-90th percentile, range: 10-44 days). Nail iron levels were measured in 300 cases and 300 controls using neutron activation analysis. A total of 24 genetic variants associated with iron status were genotyped in 622 cases and 628 controls. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk according to toenail iron and the examined genotypes. RESULTS: No association was observed between toenail iron and glioma risk when restricting to cases with nails collected within ~3 weeks of diagnosis (OR = 0.93; 95 % CI 0.46, 1.87 comparing those with high (≥14 µg/g) vs. low (<6 µg/g) iron levels). In contrast, an inverse association with increasing iron was observed after restricting to cases with a delay of 3 weeks or greater (OR = 0.42; 95 % CI 0.19, 0.95), reflecting potentially insidious effects of advancing disease on iron levels among the cases. No associations were observed for any of the examined genetic variants. CONCLUSION: The results do not support a role for body iron stores as a determinant of glioma risk.

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.

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.

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.

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.