Anthropogenic Asian aerosols provide Fe to the North Pacific Ocean.

Fossil-fuel emissions may impact phytoplankton primary productivity and carbon cycling by supplying bioavailable Fe to remote areas of the ocean via atmospheric aerosols. However, this pathway has not been confirmed by field observations of anthropogenic Fe in seawater. Here we present high-resolution trace-metal concentrations across the North Pacific Ocean (158°W from 25°to 42°N). A dissolved Fe maximum was observed around 35°N, coincident with high dissolved Pb and Pb isotope ratios matching Asian industrial sources and confirming recent aerosol deposition. Iron-stable isotopes reveal in situ evidence of anthropogenic Fe in seawater, with low δ56Fe (-0.23‰ > δ56Fe > -0.65‰) observed in the region that is most influenced by aerosol deposition. An isotope mass balance suggests that anthropogenic Fe contributes 21-59% of dissolved Fe measured between 35° and 40°N. Thus, anthropogenic aerosol Fe is likely to be an important Fe source to the North Pacific Ocean.

Preclinical Evaluation of Sodium Selenite in Mice: Toxicological and Tumor Regression Studies after Striatum Implantation of Human Glioblastoma Stem Cells.

Glioblastoma (GBM) is the most aggressive malignant glioma, with a very poor prognosis; as such, efforts to explore new treatments and GBM's etiology are a priority. We previously described human GBM cells (R2J-GS) as exhibiting the properties of cancer stem cells (growing in serum-free medium and proliferating into nude mice when orthotopically grafted). Sodium selenite (SS)-an in vitro attractive agent for cancer therapy against GBM-was evaluated in R2J-GS cells. To go further, we launched a preclinical study: SS was given orally, in an escalation-dose study (2.25 to 10.125 mg/kg/day, 5 days on, 2 days off, and 5 days on), to evaluate (1) the absorption of selenium in plasma and organs (brain, kidney, liver, and lung) and (2) the SS toxicity. A 6.75 mg/kg SS dose was chosen to perform a tumor regression assay, followed by MRI, in R2J-GS cells orthotopically implanted in nude mice, as this dose was nontoxic and increased brain selenium concentration. A group receiving TMZ (5 mg/kg) was led in parallel. Although not reaching statistical significance, the group of mice treated with SS showed a slower tumor growth vs. the control group (p = 0.08). No difference was observed between the TMZ and control groups. We provide new insights of the mechanisms of SS and its possible use in chemotherapy.

Selenium and Other Trace Elements in the Etiology of Parkinson's Disease: A Systematic Review and Meta-Analysis of Case-Control Studies.

BACKGROUND: Parkinson's disease (PD) is the most common neurodegenerative disease after Alzheimer's dementia. Whereas the exact etiology of PD remains unknown, risk of developing PD seems to be related to a combination of genetic and environmental factors. This also includes abnormal exposure to trace elements of nutritional and toxicological interest. OBJECTIVES: In this systematic review and meta-analysis, we summarized the results of case-control studies comparing levels of selenium, copper, iron, and zinc in PD patients and controls in either blood (whole blood, serum/plasma) or cerebrospinal fluid (CSF). METHODS: We performed a systematic PubMed search selecting studies reporting trace element levels in different specimens of patients and controls. We performed a meta-analysis using a random-effect model to compute the weighted mean differences (WMD) and corresponding 95% CI of selenium, copper, iron, and zinc levels in the blood or CSF of patients and their matched controls. RESULTS: We retrieved 56 papers reporting data for selenium (cases/controls: 588/721), copper (2,190/2,522), iron (2,956/3,469), and zinc (1,798/1,913) contents in CSF and blood. Cases showed considerably higher levels of selenium in CSF compared with controls (+51.6%; WMD 5.49; 95% CI 2.82 to 8.15), while levels in serum were similar (-0.2%; WMD -0.22; 95% CI -8.05 to 7.62). For copper, cases showed slightly higher levels in CSF and slightly lower concentrations in serum (+4.5%; WMD 1.87; 95% CI -3.59 to 7.33, and -4.5%; WMD -42.79; 95% CI -134.35 to 48.76, respectively). A slight increase was also found for CSF iron -levels (+9.5%; WMD 9.92; 1.23 to 18.61), while levels were -decreased in serum/plasma (-5.7%; WMD -58.19; 95% CI -106.49 to -9.89) and whole blood (-10.8%; WMD -95.69; 95% CI -157.73 to -33.65). Conversely, for zinc cases exhibited lower levels both in CSF (-10.8%; WMD -7.34; 95% CI -14.82 to 0.14) and serum/plasma (-7.5%; WMD -79.93; 95% CI -143.80 to -16.06). A longer duration of the disease tends to be associated with overall lower trace element levels in either CSF or blood. CONCLUSIONS: Due to the study findings and the greater relevance of the CSF compartment compared with the circulating peripheral ones, this meta-analysis suggests that overexposure in the central nervous system to selenium, and possibly to copper and iron, may be a risk factor of the disease, while zinc might have a protective -effect.

Comparison of Two Percutaneous Atrial Septal Defect Occluders for Device Healing and Nickel Release in a Chronic Porcine Model.

AIMS: To investigate the healing process and nickel release of the Hyperion occluder (Comed BV, Netherlands), as compared to the Amplatzer septal occluder (ASO) (St. Jude Medical Inc., St. Paul, MN, USA) in a chronic swine model. BACKGROUND: Some long-term complications occurring after percutaneous atrial septal defect (ASD) closure may be partially associated with an inappropriate healing of the device and increased nickel release. There is no direct comparative study of different occluders for healing and nickel release. METHODS: After percutaneous ASD creation, 12 pigs were implanted with 15 mm Hyperion (n = 6) and 15 mm ASO (n = 6) devices. After 1 month (n = 3 for each device) and 3 months (n = 3 for each device) of follow-up, device explantation was performed and healing was assessed using histopathological workup. Systemic and tissular nickel release was performed. RESULTS: Implantation was successful in 100% without complications. Device coverage was observed as early as 1 month after implantation and was almost complete after 3 months. A granulation tissue with a predominantly mononuclear inflammatory reaction was observed in contact with nitinol wires while an inflammatory reaction was seen in contact with textile fibers. We found no statistically significant difference between the 2 devices whether for histological grading scores or systemic nickel release, regardless to follow-up duration. CONCLUSIONS: In this preclinical study, we demonstrated that Amplatzer septal occluder and Hyperion occluder were not significantly different for device healing and nickel release processes.

Product indiscriminate use of vitamin risks: A review.

Most of the population does not seek professional advice before taking vitamin products and their indiscriminate use can lead to serious health risks. This study aims to demonstrate, through bibliographic survey, the risks of indiscriminate use of vitamin products related to hypervitaminosis and major drug interactions which the multivitamins are involved. A bibliographic survey was conducted in the databases LILACS, SciELO, PubMed, Medline, Micromedex, Drugs.com and textbooks on the subject. Vitamins are commonly described as harmless products by the majority of the population, but these trace elements can interact with other substances, causing mild disconforts or treatment failure for the patient, severe consequences to the body and can lead to death. To avoid the indiscriminate use of vitamin products, it is necessary that health professionals know and use specific laboratory tests for the determination of vitamins in the body, preventing these products from being unnecesarily prescribed. Also, the knowledge about what the possible effects of the indiscriminate use of vitamin supplements can lead to the rational use of these products.

Metformin Mitigates Nickel-Elicited Angiopoietin-Like Protein 4 Expression via HIF-1α for Lung Tumorigenesis.

Nickel (Ni), which is a carcinogenic workplace hazard, increases the risk of lung cancer. Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine that is involved in both angiogenesis and metastasis, but its role in lung cancer is still not clear. In this study, we assessed the role of ANGPTL4 in lung carcinogenesis under nickel exposure and investigated the effects of the antidiabetic drug metformin on ANGPTL4 expression and lung cancer chemoprevention. Our results showed that ANGPTL4 is increased in NiCl2-treated lung cells in a dose- and time-course manner. The expression of ANGPTL4 and HIF-1α induced by NiCl2 were significantly repressed after metformin treatment. The downregulation of HIF-1α expression by ROS savenger and HIF-1α inhibitor or knockdown by lentiviral shRNA infection diminished NiCl2-activated ANGPTL4 expression. Chromatin immunoprecipitation and the luciferase assay revealed that NiCl2-induced HIF-1α hypoxia response element interactions activate ANGPTL4 expression, which is then inhibited by metformin. In conclusion, the increased presence of ANGPTL4 due to HIF-1α accumulation that is caused by nickel in lung cells may be one mechanism by which nickel exposure contributes to lung cancer progression. Additionally, metformin has the ability to prevent NiCl2-induced ANGPTL4 through inhibiting HIF-1α expression and its binding activity. These results provide evidence that metformin in oncology therapeutics could be a beneficial chemopreventive agent.

Anemia following zinc treatment for Wilson's disease: a case report and literature review.

BACKGROUND: Zinc therapy is considered an effective and safe treatment for Wilson's disease. Hypocupremia-related anemia is rarely reported after long-term zinc administration or combination therapy with copper-chelating agent. CASE PRESENTATION: We herein report a 12-year-old girl with pre-symptomatic Wilson's disease diagnosed 5 years ago who presented with severe anemia after high-dose oral zinc for 4 years and 4 months. Her hemoglobin was gradually restored to the normal range after the adjustment of zinc dose and diet therapy for 4 months. A review of the literature revealed eight patients with hypocupremia-associated anemia following zinc therapy for Wilson's disease, including 7 adults and 1 child. The only child patient was a 16-year-old boy, in whom the zinc therapy was succession to penicillamine administration. CONCLUSIONS: This is the first report worldwide that a child developed severe anemia following high-dose single zinc administration for Wilson's disease. It highlights the importance of regular follow-up during zinc treatment and the involvement of specialists in the long-term management of Wilson's disease. We hope that this will alert pediatricians the issue of zinc over-treatment.

Peripheral axonopathy in sciatic nerve of adult Wistar rats following exposure to vanadium.

Depletion of myelin and neurobehavioural deficits are indications that vanadium crosses the blood-brain barrier and such neurotoxic effects of vanadium on the brain of Wistar rats have been elucidated. The effect however on the peripheral nerves, is yet to be reported. Thus, this work was designed to evaluate the axonal and myelin integrity of sciatic nerves in Wistar rats following exposure to vanadium. Ten male Wistar rats were exposed to 3 mg/kg body weight of sodium metavanadate for 7 days, subjected to rearing and forelimb grip behavioural tests, and sciatic nerves processed for histology (haematoxylin and eosin, cresyl violet, and luxol fast blue). Dystrophic axons with vesiculated myelin, thinned myelin sheath, and demyelinated axons were observed in the vanadium exposed rats, suggestive of axonopathy, classified as fourth-degree nerve injury. Lower behavioural scores were recorded for vanadium-dosed rats; thus, corroborating histological pictures observed of the sciatic nerves. Authors posit that vanadium crossed the "blood-nerve" barrier and caused the observed axonal pathologies and myelin depletion in the sciatic nerves of these rodents with resultant motor deficits. The present paper discusses possible motor deficits and the likely public health importance in regions with crude oil pollution and gas flaring rich in vanadium products.

Iron for the treatment of restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common neurologic disorder that is associated with peripheral iron deficiency in a subgroup of patients. It is unclear whether iron therapy is effective treatment for RLS. OBJECTIVES: To evaluate the efficacy and safety of oral or parenteral iron for the treatment of restless legs syndrome (RLS) when compared with placebo or other therapies. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycNFO, and CINAHL for the time period January 1995 to September 2017. We searched reference lists for additional published studies. We searched Clinicaltrials.gov and other clinical trial registries (September 2017) for ongoing or unpublished studies. SELECTION CRITERIA: Controlled trials comparing any formulation of iron with placebo, other medications, or no treatment, in adults diagnosed with RLS according to expert clinical interview or explicit diagnostic criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality, with discussion to reach consensus in the case of any disagreement. The primary outcome considered in this review was restlessness or unpleasant sensations, as experienced subjectively by the patient. We combined treatment/control differences in the outcomes across studies using random-effects meta-analyses. We analysed continuous data using mean differences (MDs) where possible and performed standardised mean difference (SMD) analyses when different measurements were used across studies. We calculated risk ratios (RRs) for dichotomous data using the Mantel-Haenszel method and 95% confidence intervals (CIs). We analysed study heterogeneity using the I2 statistic. We used standard methodological procedures expected by Cochrane. We performed GRADE analysis using GRADEpro. MAIN RESULTS: We identified and included 10 studies (428 total participants, followed for 2-16 weeks) in this review. Our primary outcome was restlessness or uncomfortable leg sensations, which was quantified using the International Restless Legs Scale (IRLS) (range, 0 to 40) in eight trials and a different RLS symptom scale in a ninth trial. Nine studies compared iron to placebo and one study compared iron to a dopamine agonist (pramipexole). The possibility for bias among the trials was variable. Three studies had a single element with high risk of bias, which was lack of blinding in two and incomplete outcome data in one. All studies had at least one feature resulting in unclear risk of bias.Combining data from the seven trials using the IRLS to compare iron and placebo, use of iron resulted in greater improvement in IRLS scores (MD -3.78, 95% CI -6.25 to -1.31; I2= 66%, 7 studies, 345 participants) measured 2 to 12 weeks after treatment. Including an eighth study, which measured restlessness using a different scale, use of iron remained beneficial compared to placebo (SMD -0.74, 95% CI -1.26 to -0.23; I2 = 80%, 8 studies, 370 participants). The GRADE assessment of certainty for this outcome was moderate.The single study comparing iron to a dopamine agonist (pramipexole) found a similar reduction in RLS severity in the two groups (MD -0.40, 95% CI -5.93 to 5.13, 30 participants).Assessment of secondary outcomes was limited by small numbers of trials assessing each outcome. Iron did not improve quality of life as a dichotomous measure (RR 2.01, 95% CI 0.54 to 7.45; I2=54%, 2 studies, 39 participants), but did improve quality of life measured on continuous scales (SMD 0.51, 95% CI 0.15 to 0.87; I2= 0%, 3 studies, 128 participants), compared to placebo. Subjective sleep quality was no different between iron and placebo groups (SMD 0.19, 95% CI -0.18 to 0.56; I2 = 9%, 3 studies, 128 participants), nor was objective sleep quality, as measured by change in sleep efficiency in a single study (-35.5 +/- 92.0 versus -41.4 +/- 98.2, 18 participants). Periodic limb movements of sleep were not significantly reduced with iron compared to placebo ( SMD -0.19, 95% CI -0.70 to 0.32; I2 = 0%, 2 studies, 60 participants). Iron did not improve sleepiness compared to placebo, as measured on the Epworth Sleepiness Scale (data not provided, 1 study, 60 participants) but did improve the daytime tiredness item of the RLS-6 compared to placebo (least squares mean difference -1.5, 95% CI -2.5 to -0.6; 1 study, 110 participants). The GRADE rating for secondary outcomes ranged from low to very low.Prespecified subgroup analyses showed more improvement with iron in those trials studying participants on dialysis. The use of low serum ferritin levels as an inclusion criteria and the use or oral versus intravenous iron did not show significant subgroup differences.Iron did not result in significantly more adverse events than placebo (RR 1.48, 95% CI 0.97 to 2.25; I2=45%, 6 studies, 298 participants). A single study reported that people treated with iron therapy experienced fewer adverse events than the active comparator pramipexole. AUTHORS' CONCLUSIONS: Iron therapy probably improves restlessness and RLS severity in comparison to placebo. Iron therapy may not increase the risk of side effects in comparison to placebo. We are uncertain whether iron therapy improves quality of life in comparison to placebo. Iron therapy may make little or no difference to pramipexole in restlessness and RLS severity, as well as in the risk of adverse events. The effect on secondary outcomes such as quality of life, daytime functioning, and sleep quality, the optimal timing and formulation of administration, and patient characteristics predicting response require additional study.

Perspectives on trace chemical safety and chemophobia: risk communication and risk management.

Safety issues regarding consumer products contaminated with trace amounts of chemicals are of great concern to consumers, with the degree of concern occasionally escalating to the psychological syndrome, chemophobia (i.e., the fear of chemicals). Hazardous substances frequently implicated in safety concerns include heavy metals (arsenic, mercury, cadmium, and lead), volatile organic compounds (VOC) such as benzene and o-toluidine, pesticides, carcinogens, radioactive substances, and endocrine disrupting chemicals (EDC) such as bisphenol A and phthalates. To improve communication of risk to society, members of academia, government, consumer organizations, and industry participated in this workshop to discuss and exchange perspectives on trace chemical safety. From the perspective of academia, integrated risk assessments need to be implemented to encompass various exposure sources and routes. The identification and investigation of new exposure-related biomarkers are also recommended to verify direct causal relationships between specific chemical exposure and effects on human health. As for regulation, governments need to establish and maintain acceptable limits for trace chemicals in products. In addition, harmonized efforts need to be undertaken among government agencies to share regulatory limits and effectively control trace chemicals in consumer products. Manufacturers need to faithfully abide by Good Manufacturing Practice (GMP) guidelines, monitor sources of contamination, and minimize these for consumer safety. To effectively resolve safety issues arising from trace chemicals exposure, collaborative efforts are needed involving academia, government, consumer organizations, and industry. Further, scientific evidence-based risk assessment is a critical approach to effectively manage trace chemical safety issues.

Perspectives on trace chemical safety and chemophobia: risk communication and risk management.

Safety issues regarding consumer products contaminated with trace amounts of chemicals are of great concern to consumers, with the degree of concern occasionally escalating to the psychological syndrome, chemophobia, i.e., the fear of chemicals. Hazardous substances frequently implicated in safety concerns include heavy metals (arsenic, mercury, cadmium, and lead), volatile organic compounds (VOC) such as benzene and o-toluidine, pesticides, carcinogens, radioactive substances, and endocrine disrupting chemicals (EDC) such as bisphenol A and phthalates. To improve communication of risk to society, members of academia, government, consumer organizations, and industry participated in this workshop to discuss and exchange perspectives on trace chemical safety. From the perspective of academia, integrated risk assessments need to be implemented to encompass various exposure sources and routes. The identification and investigation of new exposure-related biomarkers are also recommended to verify direct causal relationships between specific chemical exposure and effects on human health. As for regulation, governments need to establish and maintain acceptable limits for trace chemicals in products. In addition, harmonized efforts need to be undertaken among government agencies to share regulatory limits and effectively control trace chemicals in consumer products. Manufacturers need to faithfully abide by Good Manufacturing Practice (GMP) guidelines, monitor sources of contamination, and minimize these for consumer safety. To effectively resolve safety issues arising from trace chemicals exposure, collaborative efforts are needed involving academia, government, consumer organizations, and industry. Further, scientific evidence-based risk assessment is a critical approach to effectively manage trace chemical safety issues.

Effects of soil particle size on metal bioaccessibility and health risk assessment.

Oral ingestion is the main exposure pathway through which humans ingest trace metals in the soil, particularly for children. Metals in different soil particle size fractions may vary in terms of concentration and properties. Urban school/kindergarten soil samples were collected from three cities: Lanzhou in northwest China, Wuhan in central China, and Shenzhen in southeast China. Soil samples were classified according to particle size (<63 µm, 63-150 µm, 150-250 µm, and 250-2000 µm) to estimate the effects of soil particle size on the total content and bioaccessibility of metals (Cd, Cr, Cu, Ni, Pb, and Zn). Based on the results, we assessed whether the standard size <150 µm (containing < 63 µm and 63-150 µm), recommended by the Technical Review Workgroup (TRW) of the Environmental Protection Agency (EPA), and <250 µm (containing < 63 µm, 63-150 µm, and 150-250) recommended by the Bioaccessibility Research Group of Europe (BARGE), are suitable where the largest proportion adhering to hands is the finest soil (<63 µm). The results showed that different metals exhibited different relationships between soil particle size and content and between soil particle size and bioaccessibility. Pb and Zn generally exhibited the greatest bioaccessibility in the coarsest particle sizes (250-2000 µm); whereas the highest Ni bioaccessibility occurred in the finest sizes (<63 µm); the bioaccessibility of other metals did not exhibit any obvious relationships with particle size. When assessing health risks using bioaccessible metal content in the recommended soil particle size ranges (<150 µm and <250 µm) and in finer particles (<63 µm), the results for noncarcinogenic risks to children exhibited no obvious difference, while the actual carcinogenic risks may be underestimated with the use of soil particle size ranges < 150 µm and <250 µm. Therefore, when choosing an optimal particle size fraction to evaluate the health risk of oral soil ingestion, we recommend the use of the bioaccessible metal content in <63 µm soil fraction.

Intake of Trace Metals and the Risk of Incident Kidney Stones.

PURPOSE: The association between the intake of trace metals and the risk of incident stones has not been longitudinally investigated. MATERIALS AND METHODS: We performed a prospective analysis of 193,551 participants in the Health Professionals Follow-up Study, and the Nurses' Health Study I and II. During a followup of 3,316,580 person-years there was a total of 6,576 incident stones. We used multivariate regression models to identify associations of the intake of zinc, iron, copper and manganese with the risk of stones. In a subset of participants with 24-hour urine collections we examined the association between the intake of trace metals and urine composition. RESULTS: After multivariate adjustment total and dietary intakes of zinc and iron were not significantly associated with incident stones. A higher intake of manganese was associated with a lower risk of stones. The pooled HR of the highest quintile of total manganese intake compared with the lowest intake was 0.82 (95% CI 0.68-0.98, p = 0.02). Total but not dietary copper intake was marginally associated with a higher risk of stones (pooled HR 1.14, 95% CI 1.02-1.28, p = 0.01). There were no statistically significant associations of the total intake of manganese and copper with urinary supersaturation. CONCLUSIONS: Zinc and iron intake was not associated with a risk of stones. Copper intake may be associated with a higher risk in some individuals. Higher total manganese intake was associated with a lower risk of stones but not with traditional 24-hour urinary composite markers of stone risk. Further research is needed to elucidate the mechanisms by which manganese may reduce kidney stone formation.

Higher Plasma Selenium Concentrations Are Associated with Increased Odds of Prevalent Type 2 Diabetes.

Background: Selenium, an essential trace element, has been investigated as a potential cancer prevention agent. However, several studies have indicated that selenium supplementation may be associated with an increased risk of type 2 diabetes (T2D), although an equivocal relation of this nature requires confirmation. Objective: We examined the association between baseline plasma concentrations of selenium and the prevalence of T2D, as well as whether participant characteristics or intake of other antioxidant nutrients modified this relation. Methods: We conducted cross-sectional analyses of 1727 participants from the Selenium Trial, a randomized clinical trial of selenium supplementation for colorectal adenoma chemoprevention that had data for baseline selenium plasma concentrations, T2D status, and dietary intake. Logistic regression modeling was used to evaluate the associations between plasma selenium concentrations and prevalent T2D, adjusting for confounding factors. Heterogeneity of effect by participant characteristics was evaluated utilizing likelihood-ratio tests. Results: Mean ± SD plasma selenium concentrations for those with T2D compared with those without T2D were 143.6 ± 28.9 and 138.7 ± 27.2 ng/mL, respectively. After adjustment for confounding, higher plasma selenium concentrations were associated with a higher prevalence of T2D, with ORs (95% CIs) of 1.25 (0.80, 1.95) and 1.77 (1.16, 2.71) for the second and third tertiles of plasma selenium, respectively, compared with the lowest tertile (P-trend = 0.007). No significant effect modification was observed for age, sex, body mass index, smoking, or ethnicity. Increased odds of T2D were seen among those who were in the highest tertile of plasma selenium and the highest category of intake of ß-cryptoxanthin (P-trend = 0.03) and lycopene (P-trend = 0.008); however, interaction terms were not significant. Conclusions: These findings show that higher plasma concentrations of selenium were significantly associated with prevalent T2D among participants in a selenium supplementation trial. Future work is needed to elucidate whether there are individual characteristics, such as blood concentrations of other antioxidants, which may influence this relation.

Positive Iron Balance in Chronic Kidney Disease: How Much is Too Much and How to Tell?

BACKGROUND: Regulation of body iron occurs at cellular, tissue, and systemic levels. In healthy individuals, iron absorption and losses are minimal, creating a virtually closed system. In the setting of chronic kidney disease and hemodialysis (HD), increased iron losses, reduced iron absorption, and limited iron availability lead to iron deficiency. Intravenous (IV) iron therapy is frequently prescribed to replace lost iron, but determining an individual's iron balance and stores can be challenging and imprecise, contributing to uncertainty about the long-term safety of IV iron therapy. SUMMARY: Patients on HD receiving judicious doses of IV iron are likely to be in a state of positive iron balance, yet this does not appear to confer an overt risk for clinically relevant iron toxicity. The concomitant use of iron with erythropoiesis-stimulating agents, the use of maintenance iron dosing regimens, and the reticuloendothelial distribution of hepatic iron deposition likely minimize the potential for iron toxicity in patients on HD. Key Messages: Because no single diagnostic test can, at present, accurately assess iron status and risk for toxicity, clinicians need to take an integrative approach to avoid iron doses that impose excessive exposure while ensuring sufficient replenishment of iron stores capable of overcoming hepcidin blockade and allowing for effective erythropoiesis.

Linkage of national soil quality measurements to primary care medical records in England and Wales: a new resource for investigating environmental impacts on human health.

BACKGROUND: Long-term, low-level exposure to toxic elements in soil may be harmful to human health but large longitudinal cohort studies with sufficient follow-up time to study these effects are cost-prohibitive and impractical. Linkage of routinely collected medical outcome data to systematic surveys of soil quality may offer a viable alternative. METHODS: We used the Geochemical Baseline Survey of the Environment (G-BASE), a systematic X-ray fluorescence survey of soil inorganic chemistry throughout England and Wales to obtain estimates of the concentrations of 15 elements in the soil contained within each English and Welsh postcode area. We linked these data to the residential postcodes of individuals enrolled in The Health Improvement Network (THIN), a large database of UK primary care medical records, to provide estimates of exposure. Observed exposure levels among the THIN population were compared with expectations based on UK population estimates to assess representativeness. RESULTS: Three hundred seventy-seven of three hundred ninety-five English and Welsh THIN practices agreed to participate in the linkage, providing complete residential soil metal estimates for 6,243,363 individuals (92% of all current and former patients) with a mean period of prospective computerised medical data collection (follow-up) of 6.75 years. Overall agreement between the THIN population and expectations was excellent; however, the number of participating practices in the Yorkshire & Humber strategic health authority was low, leading to restricted ranges of measurements for some elements relative to the known variations in geochemical concentrations in this area. CONCLUSIONS: The linked database provides unprecedented population size and statistical power to study the effects of elements in soil on human health. With appropriate adjustment, results should be generalizable to and representative of the wider English and Welsh population.

Selenium for preventing cancer.

BACKGROUND: This review is the third update of the Cochrane review "Selenium for preventing cancer". Selenium is a naturally occurring element with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancer. OBJECTIVES: To gather and present evidence needed to address two research questions:1. What is the aetiological relationship between selenium exposure and cancer risk in humans?2. Describe the efficacy of selenium supplementation for cancer prevention in humans. SEARCH METHODS: We updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE (Ovid, 2013 to January 2017, week 4), and Embase (2013 to 2017, week 6), as well as searches of clinical trial registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and longitudinal observational studies that enrolled adult participants. DATA COLLECTION AND ANALYSIS: We performed random-effects (RE) meta-analyses when two or more RCTs were available for a specific outcome. We conducted RE meta-analyses when five or more observational studies were available for a specific outcome. We assessed risk of bias in RCTs and in observational studies using Cochrane's risk assessment tool and the Newcastle-Ottawa Scale, respectively. We considered in the primary analysis data pooled from RCTs with low risk of bias. We assessed the certainty of evidence by using the GRADE approach. MAIN RESULTS: We included 83 studies in this updated review: two additional RCTs (10 in total) and a few additional trial reports for previously included studies. RCTs involved 27,232 participants allocated to either selenium supplements or placebo. For analyses of RCTs with low risk of bias, the summary risk ratio (RR) for any cancer incidence was 1.01 (95% confidence interval (CI) 0.93 to 1.10; 3 studies, 19,475 participants; high-certainty evidence). The RR for estimated cancer mortality was 1.02 (95% CI 0.80 to 1.30; 1 study, 17,444 participants). For the most frequently investigated site-specific cancers, investigators provided little evidence of any effect of selenium supplementation. Two RCTs with 19,009 participants indicated that colorectal cancer was unaffected by selenium administration (RR 0.99, 95% CI 0.69 to 1.43), as were non-melanoma skin cancer (RR 1.16, 95% CI 0.30 to 4.42; 2 studies, 2027 participants), lung cancer (RR 1.16, 95% CI 0.89 to 1.50; 2 studies, 19,009 participants), breast cancer (RR 2.04, 95% CI 0.44 to 9.55; 1 study, 802 participants), bladder cancer (RR 1.07, 95% CI 0.76 to 1.52; 2 studies, 19,009 participants), and prostate cancer (RR 1.01, 95% CI 0.90 to 1.14; 4 studies, 18,942 participants). Certainty of the evidence was high for all of these cancer sites, except for breast cancer, which was of moderate certainty owing to imprecision, and non-melanoma skin cancer, which we judged as moderate certainty owing to high heterogeneity. RCTs with low risk of bias suggested increased melanoma risk.Results for most outcomes were similar when we included all RCTs in the meta-analysis, regardless of risk of bias. Selenium supplementation did not reduce overall cancer incidence (RR 0.99, 95% CI 0.86 to 1.14; 5 studies, 21,860 participants) nor mortality (RR 0.81, 95% CI 0.49 to 1.32; 2 studies, 18,698 participants). Summary RRs for site-specific cancers showed limited changes compared with estimates from high-quality studies alone, except for liver cancer, for which results were reversed.In the largest trial, the Selenium and Vitamin E Cancer Trial, selenium supplementation increased risks of alopecia and dermatitis, and for participants with highest background selenium status, supplementation also increased risk of high-grade prostate cancer. RCTs showed a slightly increased risk of type 2 diabetes associated with supplementation. A hypothesis generated by the Nutritional Prevention of Cancer Trial - that individuals with low blood selenium levels could reduce their risk of cancer (particularly prostate cancer) by increasing selenium intake - has not been confirmed. As RCT participants have been overwhelmingly male (88%), we could not assess the potential influence of sex or gender.We included 15 additional observational cohort studies (70 in total; over 2,360,000 participants). We found that lower cancer incidence (summary odds ratio (OR) 0.72, 95% CI 0.55 to 0.93; 7 studies, 76,239 participants) and lower cancer mortality (OR 0.76, 95% CI 0.59 to 0.97; 7 studies, 183,863 participants) were associated with the highest category of selenium exposure compared with the lowest. Cancer incidence was lower in men (OR 0.72, 95% CI 0.46 to 1.14, 4 studies, 29,365 men) than in women (OR 0.90, 95% CI 0.45 to 1.77, 2 studies, 18,244 women). Data show a decrease in risk of site-specific cancers for stomach, colorectal, lung, breast, bladder, and prostate cancers. However, these studies have major weaknesses due to study design, exposure misclassification, and potential unmeasured confounding due to lifestyle or nutritional factors covarying with selenium exposure beyond those taken into account in multi-variable analyses. In addition, no evidence of a dose-response relation between selenium status and cancer risk emerged. Certainty of evidence was very low for each outcome. Some studies suggested that genetic factors might modify the relation between selenium and cancer risk - an issue that merits further investigation. AUTHORS' CONCLUSIONS: Well-designed and well-conducted RCTs have shown no beneficial effect of selenium supplements in reducing cancer risk (high certainty of evidence). Some RCTs have raised concerns by reporting a higher incidence of high-grade prostate cancer and type 2 diabetes in participants with selenium supplementation. No clear evidence of an influence of baseline participant selenium status on outcomes has emerged in these studies.Observational longitudinal studies have shown an inverse association between selenium exposure and risk of some cancer types, but null and direct relations have also been reported, and no systematic pattern suggesting dose-response relations has emerged. These studies suffer from limitations inherent to the observational design, including exposure misclassification and unmeasured confounding.Overall, there is no evidence to suggest that increasing selenium intake through diet or supplementation prevents cancer in humans. However, more research is needed to assess whether selenium may modify the risk of cancer in individuals with a specific genetic background or nutritional status, and to investigate possible differential effects of various forms of selenium.

Acute copper overload induces vascular dysfunction in aortic rings due to endothelial oxidative stress and increased nitric oxide production.

The mechanisms involved in vascular reactivity alterations promoted by copper (Cu) overload were investigated. Thoracic aorta obtained from male Wistar rats were cut into rings and exposed for 1 h to 10 µg/ml Cu. Exposure to Cu decreased the contractile responses of aortic rings to phenylephrine (PHE). Removal of endothelium and subsequent administration of N-nitro-L arginine methyl ester (L-NAME), tetrahydrobiopterin, aminoguanidine, diethyldithiocarbamic acid, catalase, or tetraethylammonium increased contractile responses. Incubation with apocinyn and tiron enhanced the sensitivity to PHE. Data demonstrated that high concentrations of Cu reduced PHE-mediated vascular reactivity which was associated with elevated production of nitric oxide (NO), which was attributed to activation of inducible NO synthase, and elevated levels of hydrogen peroxide probably related to a rise in superoxide dismutase activity and reactive oxygen species generation.

Sequential Extractions and Toxicity Potential of Trace Metals Absorbed into Airborne Particles in an Urban Atmosphere of Southwestern Nigeria.

The paper investigates the hypothesis that biotoxicities of trace metals depend not only on the concentration as expressed by the total amount, but also on their geochemical fractions and bioavailability. Airborne particles were collected using SKC Air Check XR 5000 high volume Sampler at a human breathing height of 1.5-2.0 meters, during the dry season months from November 2014 to March 2015 at different locations in Akure (7°10'N and 5°15'E). The geochemical-based sequential extractions were performed on the particles using a series of increasingly stringent solutions selected to extract metals (Cd, Cu, Cr, Ni, Pb, Zn, and Mn) into four operational geochemical phases-exchangeable, reducible, organic, and residual-and then quantified using an Atomic Absorption Spectrophotometer. The results showed metals concentration of order Pb > Cr > Cd > Zn > Ni > Cu > Mn. However, most metals in the samples exist in nonmobile fractions: exchangeable (6.43-16.2%), reducible (32.58-47.39%), organic (4.73-9.88%), and residual (18.28-27.53%). The pollution indices show ingestion as the leading route of metal exposure, with noncarcinogenic (HQ) and cancer risk (HI) for humans in the area being higher than 1.0 × 10-4, indicating a health threat.

Investigation of the roles of trace elements during hepatitis C virus infection using protein-protein interactions and a shortest path algorithm.

BACKGROUND: Hepatitis is a type of infectious disease that induces inflammation of the liver without pinpointing a particular pathogen or pathogenesis. Type C hepatitis, as a type of hepatitis, has been reported to induce cirrhosis and hepatocellular carcinoma within a very short amount of time. It is a great threat to human health. Some studies have revealed that trace elements are associated with infection with and immune rejection against hepatitis C virus (HCV). However, the mechanism underlying this phenomenon is still unclear. METHODS: In this study, we aimed to expand our knowledge of this phenomenon by designing a computational method to identify genes that may be related to both HCV and trace element metabolic processes. The searching procedure included three stages. First, a shortest path algorithm was applied to a large network, constructed by protein-protein interactions, to identify potential genes of interest. Second, a permutation test was executed to exclude false discoveries. Finally, some rules based on the betweenness and associations between candidate genes and HCV and trace elements were built to select core genes among the remaining genes. RESULTS: 12 lists of genes, corresponding to 12 types of trace elements, were obtained. These genes are deemed to be associated with HCV infection and trace elements metabolism. CONCLUSIONS: The analyses indicate that some genes may be related to both HCV and trace element metabolic processes, further confirming the associations between HCV and trace elements. The method was further tested on another set of HCV genes, the results indicate that this method is quite robustness. GENERAL SIGNIFICANCE: The newly found genes may partially reveal unknown mechanisms between HCV infection and trace element metabolism. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.