Comparative mathematical modeling of causal association between metal exposure and development of chronic kidney disease.

Background: Previous studies have identified several genetic and environmental risk factors for chronic kidney disease (CKD). However, little is known about the relationship between serum metals and CKD risk. Methods: We investigated associations between serum metals levels and CKD risk among 100 medical examiners and 443 CKD patients in the medical center of the First Hospital Affiliated to China Medical University. Serum metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). We analyzed factors influencing CKD, including abnormalities in Creatine and Cystatin C, using univariate and multiple analysis such as Lasso and Logistic regression. Metal levels among CKD patients at different stages were also explored. The study utilized machine learning and Bayesian Kernel Machine Regression (BKMR) to assess associations and predict CKD risk based on serum metals. A chained mediation model was applied to investigate how interventions with different heavy metals influence renal function indicators (creatinine and cystatin C) and their impact on diagnosing and treating renal impairment. Results: Serum potassium (K), sodium (Na), and calcium (Ca) showed positive trends with CKD, while selenium (Se) and molybdenum (Mo) showed negative trends. Metal mixtures had a significant negative effect on CKD when concentrations were all from 30th to 45th percentiles compared to the median, but the opposite was observed for the 55th to 60th percentiles. For example, a change in serum K concentration from the 25th to the 75th percentile was associated with a significant increase in CKD risk of 5.15(1.77,8.53), 13.62(8.91,18.33) and 31.81(14.03,49.58) when other metals were fixed at the 25th, 50th and 75th percentiles, respectively. Conclusions: Cumulative metal exposures, especially double-exposure to serum K and Se may impact CKD risk. Machine learning methods validated the external relevance of the metal factors. Our study highlights the importance of employing diverse methodologies to evaluate health effects of metal mixtures.

Associations among neighborhood walkability, metal exposure, and sex steroid hormone levels: Results from Hangzhou Birth Cohort Study â ¡.

BACKGROUND: Neighborhood walkability may influence maternal-fetal exposure to environmental hazards and maternal-fetal health (e.g., fetal growth restriction, reproductive toxicity). However, few studies have explored the association between neighborhood walkability and hormones in pregnant women. METHODS: We included 533 pregnant women from the Hangzhou Birth Cohort Study II (HBCS-II) with testosterone (TTE) and estradiol (E2) measured for analysis. Neighborhood walkability was evaluated by calculating a walkability index based on geo-coded addresses. Placental metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). TTE and E2 levels in umbilical cord blood were measured using chemiluminescence microparticle immunoassay (CMIA). Linear regression model was used to estimate the relationship between the walkability index, placental metals, and sex steroid hormones. Effect modification was also assessed to estimate the effect of placental metals on the associations of neighborhood walkability with TTE and E2. RESULTS: Neighborhood walkability was significantly linked to increased E2 levels (P trend=0.023). Compared with participants at the first quintile (Q1) of walkability index, those at the third quintiles (Q3) had lower chromium (Cr) levels (ß = -0.212, 95% CI = -0.421 to -0.003). Arsenic (As), cobalt (Co), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), tin (Sn), and vanadium (V) were linked to decreased TTE levels, and cadmium (Cd) was linked to increased TTE levels. No metal was significantly associated with E2 levels in trend analysis. In the analysis of effect modification, the associations of neighborhood walkability with TTE and E2 were significantly modified by Mn (P = 0.005) and Cu (P = 0.049) respectively. CONCLUSION: Neighborhood walkability could be a favorable factor for E2 production during pregnancy, which may be inhibited by maternal exposure to heavy metals.

Elevated blood metal ion levels in patients undergoing instrumented spinal surgery: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Elevated blood metal levels have been reported in patients after spinal surgery using metallic implants. Although some studies have suggested an association between heightened blood metal concentrations and potential adverse effects, estimates of the incidence of abnormal metal levels after spinal surgery have been inconsistent. PURPOSE: The aims of this systematic review and meta-analysis were to assess: (1) mean differences in blood metal ion levels between patients undergoing spinal fusion surgery and healthy controls, (2) odds of elevated blood metal ion levels after surgery compared to presurgery levels, and (3) pooled incidence of elevated blood metal ions overall and by metal type. STUDY DESIGN: Systematic review and meta-analysis. PATIENTS SAMPLE: The patient sample included 613 patients from 11 studies who underwent spinal surgery instrumentation. OUTCOME MEASURES: Blood metal ion concentrations and the incidence of patients with elevated metal levels compared with in those the control group. METHODS: A comprehensive search was conducted in PubMed, EMBASE, Scopus, and Cochrane Library to identify studies reporting blood metal ion levels after spinal fusion surgery. Mean differences (MD), odds ratios (OR), and incidence rates were pooled using random effects models. Heterogeneity was assessed using I2 statistics, and fixed-effects models were used if no heterogeneity was detected. Detailed statistical analysis was performed using the Review Manager version 5.4 software. RESULTS: The analysis included 11 studies, with a total of 613 patients. Mean blood metal ion levels were significantly higher after spinal fusion surgery (MD 0.56, 95% CI 0.17-0.96; I2=86%). Specifically, titanium levels were significantly elevated (MD 0.81, 95% CI 0.32-1.30; I2=47%). The odds of elevated blood metal ions were higher after surgery (OR 8.17, 95% CI 3.38-19.72; I2=41%), primarily driven by chromium (OR 23.50, 95% CI 5.56-99.31; I2=30%). The incidence of elevated chromium levels was found to be 66.98% (95% CI 42.31-91.65). CONCLUSION: In conclusion, blood metal ion levels, particularly titanium and chromium, were significantly increased after spinal fusion surgery compared to presurgery levels and healthy controls. Approximately 70% of the patients exhibited elevated blood levels of chromium and titanium.

Serum and tissue metallome of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) patients have late presentation at the time of diagnosis and a poor prognosis. Metal dyshomeostasis is known to play a role in cancer progression. However, the blood and tissue metallome of PDAC patients has not been assessed. This study aimed to determine the levels of essential and toxic metals in the serum and pancreatic tissue from PDAC patients. Serum samples were obtained from PDAC patients before surgical resection. Tissue (tumor and adjacent normal pancreas) were obtained from the surgically resected specimen. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis was performed to quantify the levels of 10 essential and 3 toxic metals in these samples. Statistical analysis was performed to identify dysregulated metals in PDAC and their role as potential diagnostic and prognostic biomarkers. Significantly decreased serum levels of magnesium, potassium, calcium, iron, zinc, selenium, arsenic, and mercury and increased levels of molybdenum were shown to be associated with PDAC. There were significantly decreased levels of zinc, manganese and molybdenum, and increased levels of calcium and selenium in the pancreatic tumor tissue compared with the adjacent normal pancreas. Notably, lower serum levels of calcium, iron, and selenium, and higher levels of manganese, were significantly associated with a poor prognosis (i.e., overall survival) in PDAC patients. In conclusion, this is the first study to comprehensively assess the serum and tissue metallome of PDAC patients. It identified the association of metals with PDAC diagnosis and prognosis.

Recent advances in the application of metallomics in diagnosis and prognosis of human cancer.

Metals play a critical role in human health and diseases. In recent years, metallomics has been introduced and extensively applied to investigate the distribution, regulation, function, and crosstalk of metal(loid) ions in various physiological and pathological processes. Based on high-throughput multielemental analytical techniques and bioinformatics methods, it is possible to elucidate the correlation between the metabolism and homeostasis of diverse metals and complex diseases, in particular for cancer. This review aims to provide an overview of recent progress made in the application of metallomics in cancer research. We mainly focuses on the studies about metallomic profiling of different human biological samples for several major types of cancer, which reveal distinct and dynamic patterns of metal ion contents and the potential benefits of using such information in the detection and prognosis of these malignancies. Elevated levels of copper appear to be a significant risk factor for various cancers, and each type of cancer has a unique distribution of metals in biofluids, hair/nails, and tumor-affected tissues. Furthermore, associations between genetic variations in representative metalloprotein genes and cancer susceptibility have also been demonstrated. Overall, metallomics not only offers a better understanding of the relationship between metal dyshomeostasis and the development of cancer but also facilitates the discovery of new diagnostic and prognostic markers for cancer translational medicine.

Maternal blood metal concentrations and whole blood DNA methylation during pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI).

The maternal epigenome may be responsive to prenatal metals exposures. We tested whether metals are associated with concurrent differential maternal whole blood DNA methylation. In the Early Autism Risk Longitudinal Investigation cohort, we measured first or second trimester maternal blood metals concentrations (cadmium, lead, mercury, manganese, and selenium) using inductively coupled plasma mass spectrometry. DNA methylation in maternal whole blood was measured on the Illumina 450 K array. A subset sample of 97 women had both measures available for analysis, all of whom did not report smoking during pregnancy. Linear regression was used to test for site-specific associations between individual metals and DNA methylation, adjusting for cell type composition and confounding variables. Discovery gene ontology analysis was conducted on the top 1,000 sites associated with each metal. We observed hypermethylation at 11 DNA methylation sites associated with lead (FDR False Discovery Rate q-value <0.1), near the genes CYP24A1, ASCL2, FAT1, SNX31, NKX6-2, LRC4C, BMP7, HOXC11, PCDH7, ZSCAN18, and VIPR2. Lead-associated sites were enriched (FDR q-value <0.1) for the pathways cell adhesion, nervous system development, and calcium ion binding. Manganese was associated with hypermethylation at four DNA methylation sites (FDR q-value <0.1), one of which was near the gene ARID2. Manganese-associated sites were enriched for cellular metabolism pathways (FDR q-value<0.1). Effect estimates for DNA methylation sites associated (p < 0.05) with cadmium, lead, and manganese were highly correlated (Pearson ρ > 0.86). DNA methylation sites associated with lead and manganese may be potential biomarkers of exposure or implicate downstream gene pathways.

Increased aluminum and lithium and decreased zinc levels in plasma is related to cognitive impairment in workers at an aluminum factory in China: A cross-sectional study.

BACKGROUND: Previous studies have shown that multiple imbalances of metal ions in the brain are closely associated with the neurodegenerative disorders. Our studies have shown that long-term working exposure to aluminum induces increased plasma aluminum levels and causes cognitive impairment in workers at aluminum factories. OBJECTIVE: To explore the levels of nine metals in plasma and the effect on cognitive function among in-service workers. METHODS: In this cross-sectional study, cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), which included seven subitems: executive/visuospatial abilities; naming; attention and calculation; language; abstract; recall; and orientation. The plasma levels of nine kinds of metals were measured by inductively coupled plasma-mass spectrometry (ICP-MS). A multivariate generalized linear regression model and Bayesian kernel machine regression (BKMR) were selected to estimate the relationship between metal plasma level and MoCA scores with adjustment for confounders. RESULTS: One hundred and eighty-seven workers participated in this study. In the multivariable generalized linear model, among these nine metals studied, five were related to the MoCA score: aluminum, lithium, cobalt, zinc and chromium. In the BKMR model, a significantly negative correlation between the plasma aluminum, lithium and the total MoCA score was observed. Moreover, for subitems on the MoCA scale, the plasma levels of lithium, aluminum, and zinc had a significant correlation with the executive/visuospatial abilities, naming, and orientation abilities, respectively. The log-transformation concentrations of plasma aluminum and lithium were negatively correlated with the executive/visuospatial abilities and naming abilities, respectively. The log-transformation plasma zinc concentration was positively correlated with orientation abilities. CONCLUSION: Based on the results, we determined that increased aluminum and lithium and decreased zinc levels in plasma were associated with the incidence of mild cognitive impairment (MCI) in workers at a Chinese aluminum plant.

Serum and urinary concentrations of arsenic, beryllium, cadmium and lead after an aerobic training period of six months in aerobic athletes and sedentary people.

AIM: The aim of the present study was to evaluate the possible effect of a period of 6 months of aerobic physical training on serum and urinary concentrations of arsenic (As), beryllium (Be), cadmium (Cd) and lead (Pb), potentially toxic minerals. METHODS: Twenty-four well-trained, long distance runners (AG), were recruited at the start of their training period. They had been performing training regularly for the previous 2 years, recording an average volume of 120 km per week of rigorous aerobic exercise aimed at high-level competitions (1500 and 5000 m race modalities). Twenty-six untrained, sedentary participants constituted the control group (CG). All participants had been living in the same geographic area for at least 2 years before the start of the survey. Serum and urine samples were obtained from each participant at the beginning and at the end of the 6 months of the training program. The values of each mineral were determined by inductively coupled plasma mass spectrometry (ICP-MS). Additionally, the daily intake of each mineral was evaluated at both moments in time. RESULTS: The daily concentrations of trace elements in the diet were similar at the start and the end of the training period without differences between groups. In serum, significant differences between groups were observed in As, Cd and Pb (p < 0.05). Attending to time effects, a significant difference was obtained in Pb (p < 0.05). In urine, significant differences between groups were obtained in all minerals (p < 0.05). According to training period, significant differences were observed in As, Be and Pb (p < 0.05). Finally, the group x time interaction revealed significant differences in As and Be (p < 0.05). CONCLUSIONS: Aerobic training may constitute a possibly effective method for increasing the elimination of Cd and Pb potentially toxic minerals from the body, especially among highly trained individuals.

Biological Monitoring of Metal Ions Released from Hip Prostheses.

The aim of this study was to evaluate the levels of As, Be, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V, and Zn, by inductively coupled plasma-mass spectrometry (ICP-MS) in the urine of two groups of patients with two different types of metal-on-metal (MoM) total hip prostheses (ASR DePuy®, group A, 25 patients; total Met-Met System Lima®, group B, 28 patients). The determination of metals reflected a steady-state release (group A: 9 years after surgery and group B: 6 years after surgery). The results obtained confirmed the increase of Co and Cr urinary levels in both group when compared with the reference values for the general population adopted by the Italian Society of Reference Values (SIVR). In particular, Co and Cr levels exceeded the threshold values in urine, respectively, of 30 µg and 21 µg, adjusted to creatinine based on the threshold in whole blood of 7 µg/L proposed by the Medicines and Healthcare Products Regulatory Agency (MHRA). Regarding the other investigated metals, significantly higher values were found in Group A than in Group B. These differences could be due to the type of hip prosthesis implanted, the longer period of time since the implantation, as well as many other factors such as diet, age, drug consumption, physical activity, or presence of dental fillings. The continuous monitoring over the years of metal concentrations in patients carrying a prosthesis could be useful to better identify the sources of these metals.

Metal/Metalloid Levels in Electronic Cigarette Liquids, Aerosols, and Human Biosamples: A Systematic Review.

BACKGROUND: Electronic cigarettes (e-cigarettes) have become popular, in part because they are perceived as a safer alternative to tobacco cigarettes. An increasing number of studies, however, have found toxic metals/metalloids in e-cigarette emissions. OBJECTIVE: We summarized the evidence on metal/metalloid levels in e-cigarette liquid (e-liquid), aerosols, and biosamples of e-cigarette users across e-cigarette device systems to evaluate metal/metalloid exposure levels for e-cigarette users and the potential implications on health outcomes. METHODS: We searched PubMed/TOXLINE, Embase®, and Web of Science for studies on metals/metalloids in e-liquid, e-cigarette aerosols, and biosamples of e-cigarette users. For metal/metalloid levels in e-liquid and aerosol samples, we collected the mean and standard deviation (SD) if these values were reported, derived mean and SD by using automated software to infer them if data were reported in a figure, or calculated the overall mean (mean ± SD) if data were reported only for separate groups. Metal/metalloid levels in e-liquids and aerosols were converted and reported in micrograms per kilogram and nanograms per puff, respectively, for easy comparison. RESULTS: We identified 24 studies on metals/metalloids in e-liquid, e-cigarette aerosols, and human biosamples of e-cigarette users. Metal/metalloid levels, including aluminum, antimony, arsenic, cadmium, cobalt, chromium, copper, iron, lead, manganese, nickel, selenium, tin, and zinc, were present in e-cigarette samples in the studies reviewed. Twelve studies reported metal/metalloid levels in e-liquids (bottles, cartridges, open wick, and tank), 12 studies reported metal/metalloid levels in e-cigarette aerosols (from cig-a-like and tank devices), and 4 studies reported metal/metalloid levels in human biosamples (urine, saliva, serum, and blood) of e-cigarette users. Metal/metalloid levels showed substantial heterogeneity depending on sample type, source of e-liquid, and device type. Metal/metalloid levels in e-liquid from cartridges or tank/open wicks were higher than those from bottles, possibly due to coil contact. Most metal/metalloid levels found in biosamples of e-cigarette users were similar or higher than levels found in biosamples of conventional cigarette users, and even higher than those found in biosamples of cigar users. CONCLUSION: E-cigarettes are a potential source of exposure to metals/metalloids. Differences in collection methods and puffing regimes likely contribute to the variability in metal/metalloid levels across studies, making comparison across studies difficult. Standardized protocols for the quantification of metal/metalloid levels from e-cigarette samples are needed. https://doi.org/10.1289/EHP5686.

Blood Metal Ion Release After Primary Total Knee Arthroplasty: A Prospective Study.

OBJECTIVES: To investigate the course of in vivo blood metal ion levels in patients undergoing primary total knee arthroplasty (TKA) and to investigate potential risk factors associated with metal ion release in these patients. METHODS: Twenty-five patients with indication for TKA were included in this prospective study. Whole blood metal ion analysis was performed pre-operatively and at 1 week, 6 weeks, 3 months, 6 months, and 12 months postoperatively. Clinical scores were obtained using the American Knee Society Score (AKSS) and the Oxford Knee Score (OKS) at each follow-up and patients' activity levels were assessed by measuring the mean annual walking cycles at 12 months follow-up. Anteroposterior and lateral radiographs of the operated knee were evaluated postoperatively and at 12-month follow-up with regard to implant position and radiological signs of implant loosening. Correlation analysis using multivariate linear regression was performed to investigate the influence of different variables (age, gender, functional scores, number of walking cycles, and body mass index [BMI]) on blood cobalt ion concentrations. RESULTS: Mean metal ion levels of cobalt, chromium, molybdenum, and titanium were 0.28 µg/L (SD, 0.14), 0.43 µg/L (SD, 0.49), 0.62 µg/L (SD, 0.45), and 1.96 µg/L (SD, 0.98), respectively at 12-month follow-up. Mean cobalt ion levels significantly increased 1-year after surgery compared to preoperative measurements. There was no statistically significant increase of mean metal ion levels of chromium, titanium, and molybdenum at 1-year follow-up. Overall, metal ion levels were low and no patient demonstrated cobalt ion levels above 1 µg/L. Postoperative radiographs demonstrated well-aligned TKAs in all patients and no signs of osteolysis or implant loosening were detected at 1-year follow-up. Both the AKSS and OKS significantly improved during the course of the study up to the final follow-up. Multivariate regression analysis did not show a statistically significant correlation between the tested variables and blood cobalt ion concentrations. CONCLUSION: A statistically significant increase of mean cobalt ion concentration at 1-year follow-up was found in this cohort of patients with well-functioning TKA, although overall blood metal ion levels were relatively low. Despite low systemic metal ion concentrations seen in this cohort, the local effects of increased metal ion concentrations in the periprosthetic environment on the long-term outcome of TKA should be further investigated.

Regional variations in human chemical exposures in Canada: A case study using biomonitoring data from the Canadian Health Measures Survey for the provinces of Quebec and Ontario.

The Canadian Health Measures Survey (CHMS), an ongoing national health survey conducted in two-year cycles, collects extensive biomonitoring data that is used to assess the exposure of Canadians to environmental chemicals of concern. Combining data from multiple cycles of the CHMS allows for the calculation of robust regional estimates of chemical concentrations in blood and urine. The objective of this work was to compare biomarkers of exposure to several environmental chemicals for the provinces of Quebec and Ontario, two major CHMS regions, as well as the entire CHMS (representing Canada) minus Quebec (CMQ), and the entire CHMS minus Ontario (CMO), and to interpret differences between regions. Geometric means and 95th percentiles of blood and/or urinary concentrations of 45 environmental chemicals or their metabolites for Ontario, Quebec, CMQ, and CMO were calculated by combining the two most recent cycles of data available for a chemical (cycles 1 and 2, or cycles 2 and 3) from the first three cycles of the CHMS (2007-2013). Weighted one-way ANOVA was used to test the differences between regional estimates. After applying a Bonferonni-Holm adjustment for multiple comparisons, the following measures were significantly higher in Quebec as compared to Ontario and CMQ: blood lead, urinary lead and the urinary polyaromatic hydrocarbon (PAH) metabolites, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2- hydroxyphenanthrene and 3-hydroxyphenanthrene. In Quebec compared to CMQ only, urinary 2-hydroxfluorene, 3-hydroxyfluorene, 2-hydroxynaphthalene, and 4-hydroxyphenanthrene were higher. The concentration of urinary fluoride was significantly higher in Ontario as compared to Quebec and CMO. Blood manganese and urinary fluoride were significantly lower in Quebec compared to CMQ, and blood and urinary selenium were significantly lower in Ontario compared to CMO. Regional differences in tobacco use, age of dwellings and drinking water fluoridation are among the possible contributing factors to some of the observed differences. In conclusion, this is the first study where biomonitoring data from multiple cycles of CHMS were combined in order to generate robust estimates for subsets of the Canadian population. Such assessments can contribute to a regional-level prioritization of control measures to reduce the exposure of Canadians to chemicals in their environment.

A Metallomic Approach to Assess Associations of Serum Metal Levels With Gallstones and Gallbladder Cancer.

BACKGROUND AND AIMS: Exposure to metals may promote the risk for cancers. We evaluated the associations of a broad spectrum of metals with gallbladder cancer (GBC) and gallstones. APPROACH AND RESULTS: A total of 259 patients with GBC, 701 patients with gallstones, and 851 population-based controls were enrolled in Shanghai, China. A metallome panel was used to simultaneously detect 18 metals in serum through inductively coupled plasma-mass spectrometry. Logistic regression models were used to estimate crude or adjusted odds ratios (ORadj ) with 95% confidence intervals (CIs) for the association between metal levels and gallbladder disease. Among the 18 metals tested, 12 were significantly associated with GBC and six with gallstones (Pcorrected  < 0.002). Boron, lithium, molybdenum, and arsenic levels were associated with GBC compared to gallstones as well as with gallstones compared to population-based controls. Elevated levels of cadmium, chromium, copper, molybdenum, and vanadium were positively associated with GBC versus gallstones; and the ORadj for the highest tertile (T3) compared to the lowest tertile (T1) ranged from 1.80 to 7.28, with evidence of dose-response trends (P < 0.05). Arsenic, boron, iron, lithium, magnesium, selenium, and sulfur were inversely associated with GBC, with the T3 versus T1 ORadj ranging from 0.20 to 0.69. Arsenic, boron, calcium, lithium, molybdenum, and phosphorus were negatively associated with gallstones, with the T3 versus T1 ORadj ranging from 0.50 to 0.75 (P < 0.05). CONCLUSIONS: Metals were associated with both GBC and gallstones, providing cross-sectional evidence of association across the natural history of disease. Longitudinal studies are needed to evaluate the temporality of metal exposure and gallbladder diseases and to investigate the mechanisms of disease pathogenesis.

Associations of plasma metal concentrations with the decline in kidney function: A longitudinal study of Chinese adults.

Metals are widespread pollutants in the environment which have been reported to be associated with kidney dysfunction in many existing epidemiological studies. However, most of the studies are cross-sectional design and mainly focus on several toxic metals including arsenic, lead and cadmium. Therefore, we conducted this prospective study within the Dongfeng-Tongji cohort to evaluate the associations of plasma multiple metals with the decline in kidney function among Chinese middle-aged and elderly. In total, 1434 participants free of chronic diseases at baseline were included in analysis. We measured baseline plasma concentrations of 23 metals and calculated estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on serum creatinine, age, sex and ethnicity. Bonferroni correction was used for multiple testing to reduce the probability of a type I error. Principal component analysis was conducted to evaluate the combined effect of multiple metal co-exposure. Most of the plasma metal concentrations were within the literature reported reference values, whereas the concentration of lead and nickel exceeded the guideline value. We found that plasma concentrations of aluminum, arsenic, barium, lead, molybdenum, rubidium, strontium, vanadium and zinc were significantly associated with the decline in kidney function measured by annual eGFR decline, rapid renal function decline (defined as an annual decline in eGFR ≥ 5 mL/min/1.73 m2) or incident eGFR < 60 mL/min/1.73 m2, with the adjusted beta coefficients (95% CI) for annual eGFR decline 0.50 (0.30, 0.69), 0.98 (0.74, 1.23), 0.56 (0.32, 0.79), 0.21 (0.03, 0.39), 0.35 (0.16, 0.54), 0.94 (0.71, 1.17), 0.37 (0.15, 0.60), 0.78 (0.54, 1.02), and 0.74 (0.57, 0.91), respectively. The metals exposures were linked with increased risks of impaired kidney function. Associations of principal components representing these metals with the decline in kidney function were significant and suggest a possible additional health risk by co-exposure. Participants engaged in manufacturing had higher plasma levels of several metals compared with those who had been involved in management- or administration-related work. Our findings suggest that exposure to multiple metals contribute to the decline in kidney function among the middle-aged and elderly. Co-exposure to multiple metals may have synergetic effect on the kidney function. Further studies are warranted to confirm our findings and clarify the potential mechanisms.

Metallomics-based platforms for comparing the human blood serum profiles between bipolar disorder and schizophrenia patients.

RATIONALE: An evaluation of bipolar disorder (BD) and schizophrenia (SCZ) was carried out, from a metallomics point of view, using native conditions, attempting to preserve the interaction between metals and biomolecules. METHOD: For this task, blood serum samples from healthy individuals and patients were compared. In addition, the profiles of metal ions and metalloids involved in the pathologies were quantified, and a comparison was carried out of the protein profile in serum samples of healthy individuals and diseased patients. RESULTS: After optimization and accuracy evaluation of the method, different concentrations of Li, Mg, Mn and Zn were observed in the samples of BD patients and high levels of copper for SCZ patients, indicating an imbalance in the homeostasis of important micronutrients. The treatment, especially with lithium, may be related to competition between metallic ions. BD-related metallobiomolecules were detected, preserving the binding between metal ions and biomolecules, with four fractions detected in the ultraviolet range (280 nm). Four fractions were collected by high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICP-MS) and the proteins were identified by liquid chromatography/tandem mass spectrometry (LC/MS/MS). The Ig lambda chain V-IV region Hil, immunoglobulin heavy constant gama 1 (IGHG1) and beta-2-glycoprotein 1 (or ApoH) was identified in SCZ samples, suggesting its relationship with mood disorders. Surprisingly, Protein IGKV2D-28 was identified only in BD samples, opening up new possibilities for studies regarding the role of this protein in BD. CONCLUSIONS: This approach brings new perspectives to the comprehension of mood disorders, highlighting the importance of metallomics science in disease development. This strategy showed an innovative potential for evaluating mood disorders at the proteomic level, making it possible to identify proteins related to mood disorders and BD.

Exposure to metal fumes and circulating miRNAs in Algerian welders.

PURPOSE: A cross-sectional study was conducted in a group of Algerian welders to study the relationship between the exposure to metal particles from welding fumes and the concentration of three circulating miRNAs, miR-21, miR-146a and miR-155, as markers of renal function injury. METHODS: Characteristics of the subjects and the curriculum laboris were determined by questionnaires. We measured the concentrations of metals in blood and urine samples using ICP-MS. The three circulating miRNAs studied were measured by quantitative PCR. Associations between miRNAs and internal exposure markers were assessed by simple and multiple regression analyses. RESULTS: miR-21 was significantly lower among welders (p = 0.017), compared with controls, adjusted for age, body mass index, smoking status and seniority. Significant adjusted associations were observed between miR-21 or miR-155 and urinary chromium (p = 0.005 or p = 0.041, respectively), miR-146a and urinary nickel (p = 0.019). The results of the multivariate analysis showed that duration of employment was the main factor responsible for the variation of miRNAs among welders. CONCLUSION: In conclusion, a recent exposure to certain metals, mainly chromium and nickel, appears to be associated to a decrease in plasma expression of miR-21, miR-146a and miR-155. Further larger studies would help to determine the mechanisms of action of metal particles on miRNA expression.

The Association of Serum TNF-α Levels and Blood Multi-Elements Modified by TNF-α Gene Polymorphisms in Metal Industrial Workers.

Health of the metal industrial workers should be a noteworthy issue due to the hazard ofchronic exposure to metals or toxic elements. The interactions among multiple elements aresophisticated and may differ from person to person. Tumor necrosis factor-α (TNF-α) genepolymorphisms were supposed to be involved with the interactions because TNF-α plays animportant role in inflammation, a mechanism by which toxic elements cause threats to humanhealth. This research aimed to analyze the influence of TNF-αgene polymorphisms and multielementson serum TNF-α level. Blood multi-elements concentrations (lead, cadmium, arsenic,selenium, cobalt, copper, and zinc), serum TNF-α level, and TNF-α single nucleotidepolymorphisms (SNPs), including -238G > A (rs361525), -308G > A (rs1800629), -857C > T(rs1799724), -863C > A (rs1800630), and -1031T > C (rs1799964), were measured in 462 metalindustrial workers. We applied mixed-effect models to analyze the interactions among multielementsand TNF-α SNPs. Blood concentration of all elements were positively associated withserum TNF-α level, and the effects may be modified by TNF-α gene polymorphisms. Our studyrevealed that TNF-α -308A/A and -1031C/C may be susceptible genotypes, and thus we suggestthat those workers should take preventive measures against metal toxicity.

Nutraceutical effect of vitamins and minerals on performance and immune and antioxidant systems in dairy calves during the nutritional transition period in summer.

We aimed to determine whether the use of injectable vitamins and minerals improves growth performance and immune and antioxidant responses in dairy calves during pre- and post-weaning period in summer. Twenty dairy calves (45 days of age) were randomized to two groups (10 each): control group (CON) and treated group [TREAT; injection providing 0.20, 0.80, 0.20, 0.10, 35 and 1 mg/kg of copper, zinc, manganese selenium, and vitamins A and E, during two periods (15 days pre- and 15 days post-weaning)]. The animals were weighed and blood samples were collected on days 1, 15, 30 and 45 of the study. Levels of serum copper, selenium, zinc, and manganese were measured on day 1; and the results showed that calves were not deficient in these minerals. The TREAT group had greater BW gain during the final third of the experiment. There was an increase in total leukocyte numbers as a result of elevation in neutrophil counts (day 45) and monocytes (days 30 and 45) in the TREAT group. This group also had lower reactive oxygen species (ROS) content (days 15, 30 and 45) and lipid peroxidation (LPO; days 15 and 45). Furthermore, the TREAT group had greater antioxidant capacity against peroxyl radicals (ACAP; days 15 and 30), activities of the enzymes glutathione peroxidase (GPx; days 15, 30 and 45) and superoxide dismutase (SOD; day 15), concentrations of total serum proteins (day 30), serum globulin (days 15 and 30), ceruloplasmin (day 15), tumor necrosis factor-alpha (TNF-α), interleukin-1, (IL-1; days 30 and 45) and interferon gamma (IFNγ; day 45), compared to CON group. High respiratory rates during hot times of the day in all study calves was suggestive of heat stress. Taken together, the data suggest that mineral and vitamins injections increased the growth performance and boosted the antioxidant and immunological systems of dairy calves during the diet transition period in summer.

Exposure profile of mercury, lead, cadmium, arsenic, antimony, copper, selenium and zinc in maternal blood, cord blood and placenta: the Tohoku Study of Child Development in Japan.

BACKGROUND: The effects of prenatal exposure to toxic elements on birth outcomes and child development have been an area of concern. This study aimed to assess the profile of prenatal exposure to toxic elements, arsenic (As), bismuth (Bi), cadmium (Cd), mercury (total mercury (THg), methylmercury (MHg), inorganic mercury (IHg)), lead (Pb), antimony (Sb) and tin (Sn), and essential trace elements, copper (Cu), selenium (Se) and zinc (Zn), using the maternal blood, cord blood and placenta in the Tohoku Study of Child Development of Japan (N = 594-650). METHODS: Inductively coupled plasma mass spectrometry was used to determine the concentrations of these elements (except mercury). Levels of THg and MeHg were measured using cold vapour atomic absorption spectrophotometry and a gas chromatograph-electron capture detector, respectively. RESULTS: Median concentrations (25th-75th) of As, Cd, Pb, Sb, Sn and THg in the maternal blood were 4.06 (2.68-6.81), 1.18 (0.74-1.79), 10.8 (8.65-13.5), 0.2 (0.06-0.40) and 0.2 (0.1-0.38) ng mL-1 and 5.42 (3.89-7.59) ng g-1, respectively. Median concentrations (25th-75th) of As, Cd, Pb, Sb, Sn and THg in the cord blood were 3.68 (2.58-5.25), 0.53 (0.10-1.25), 9.89 (8.02-12.5), 0.39 (0.06-0.92) and 0.2 (0.2-0.38) ng mL-1 and 9.96 (7.05-13.8) ng g-1, respectively. CONCLUSIONS: THg and Sb levels in the cord blood were twofold higher than those in the maternal blood. Cord blood to maternal blood ratios for As, Cd and Sb widely varied between individuals. To understand the effects of prenatal exposure, further research regarding the variations of placental transfer of elements is necessary.

Pregnant Inuit Women's Exposure to Metals and Association with Fetal Growth Outcomes: ACCEPT 2010⁻2015.

Environmental contaminants such as heavy metals are transported to the Arctic regions via atmospheric and ocean currents and enter the Arctic food web. Exposure is an important risk factor for health and can lead to increased risk of a variety of diseases. This study investigated the association between pregnant women's levels of heavy and essential metals and the birth outcomes of the newborn child. This cross-sectional study is part of the ACCEPT birth cohort (Adaption to Climate Change, Environmental Pollution, and dietary Transition) and included 509 pregnant Inuit women ≥18 years of age. Data were collected in five Greenlandic regions during 2010⁻2015. Population characteristics and birth outcomes were obtained from medical records and midwives, respectively, and blood samples were analyzed for 13 metals. Statistical analysis included one-way ANOVA, Spearman's rho, and multiple linear and logistic regression analyses. The proportion of current smokers was 35.8%. The levels of cadmium, chromium, and nickel were higher compared to reported normal ranges. Significant regional differences were observed for several metals, smoking, and parity. Cadmium and copper were significantly inversely related to birth outcomes. Heavy metals in maternal blood can adversely influence fetal development and growth in a dose⁻response relationship. Diet and lifestyle factors are important sources of toxic heavy metals and deviant levels of essential metals. The high frequency of smokers in early pregnancy is of concern, and prenatal exposure to heavy metals and other environmental contaminants in the Greenlandic Inuit needs further research.