Blood Mn Levels Research Articles

Cotinine exposure enhances the association of blood manganese and non-alcoholic fatty liver disease in American children: a cross-sectional study

This cross-sectional survey aims to determine whether cotinine exposure would enhance the relationship between blood manganese (Mn) and non-alcoholic fatty liver disease (NAFLD) in children using the NHANES database. Restricted cubic spline (RCS) and logistic regression analyses were adopted to determine the potential relationship. Besides, we tested the robustness of the results by performing trend tests and subgroup analyses. The study finally enrolled 866 children aged 18 years and below. Blood Mn was linearly linked to NAFLD and the risk of NAFLD was increased with the blood Mn elevation (P < 0.05). There was a notable relationship between blood Mn and NAFLD in crude model 1, which was still significant upon adjustment of all the identified covariates (all P < 0.05). Under Mn exposure, the cotinine-exposed group had a higher risk of NAFLD than the cotinine-unexposed group. In conclusion, blood Mn level is an independent risk factor for pediatric NAFLD, and cotinine exposure can enhance this relationship to some degree. Therefore, reducing cotinine exposure may alleviate detrimental consequences related to exposure to heavy metals in children.

Effects of Mixed Metal Exposure on MRI Metrics in Basal Ganglia.

Welding fumes contain various metals. Past studies, however, mainly focused on Manganese (Mn)-related neurotoxicity. This study investigated welding-related mixed metal exposure effects on MRI metrics in the basal ganglia (BG) and their dose-response relationship. Subjects with (N = 23) and without (N = 24) a welding exposure history were examined. Metal exposure was estimated with exposure history questionnaire and whole blood metal levels. T1 (weighted-intensity and relaxation time; estimates of brain Mn accumulation), diffusion tensor imaging [Axial (AD), mean (MD), radial diffusivity (RD), and fractional anisotropy (FA); estimates of microstructural differences] metrics in BG [caudate nucleus, putamen, and globus pallidus (GP)] and voxel-based morphometry (for volume) were examined and related with metal exposure measures. Compared to controls, welders showed higher GP R1 (1/T1; p = 0.034) but no differences in blood metal and T1-weighted (T1W) values in any ROIs (p's > 0.120). They also had higher AD and MD values in the GP (p's < 0.033) but lower FA values in the putamen (p = 0.039) with no morphologic differences. In welders, higher blood Mn and Vanadium (V) levels predicted higher BG R1 and T1W values (p's < 0.015). There also were significant overall metal mixture effects on GP T1W and R1 values. Moreover, GP AD and MD values showed non-linear associations with BG T1W values: They increased with increasing T1W values only above certain threshold of T1 values. The current findings suggest that Mn and V individually but also metal mixtures jointly predict GP T1 signals that may in turn contribute to altered DTI metrics in the BG after certain exposure threshold levels.

Higher blood manganese level associated with increased risk of adult latent tuberculosis infection in the US population.

The associations between blood heavy metal levels and latent tuberculosis infection (LTBI) have not been fully elucidated. The aim of this study was to investigate the potential association between blood heavy metal levels and LTBI in adults using National Health and Nutrition Examination Survey data from 2011 to 2012. We enrolled 1710 participants in this study, and compared the baseline characteristics of participants involved. Multivariate logistic regression analysis, restricted cubic splines (RCS) analysis, along with subgroup analysis and interaction tests were utilized to explore the association between blood manganese (Mn) level and LTBI risk. Participants with LTBI had higher blood Mn level compared to non-LTBI individuals (p < 0.05), while the levels of lead, cadmium, total mercury, selenium, copper, and zinc did not differ significantly between the two groups (p > 0.05). In the fully adjusted model, a slight increase in LTBI risk was observed with each 1-unit increase in blood Mn level (OR = 1.00, 95% CI: 1.00-1.01, p = 0.02). Participants in the highest quartile of blood Mn level had a threefold increase in LTBI risk compared to those in the lowest quartile (OR = 4.01, 95% CI: 1.22-11.33, p = 0.02). RCS analysis did not show a non-linear relationship between blood Mn level and LTBI (non-linear p-value = 0.0826). Subgroup analyses and interaction tests indicated that age, alcohol consumption, and income-to-poverty ratio significantly influenced LTBI risk (interaction p-values<0.05). Individuals with LTBI had higher blood Mn level compared to non-LTBI individuals, and higher blood Mn level associated with increased LTBI risk.

The manganese transporter SLC39A8 links alkaline ceramidase 1 to inflammatory bowel disease

The metal ion transporter SLC39A8 is associated with physiological traits and diseases, including blood manganese (Mn) levels and inflammatory bowel diseases (IBD). The mechanisms by which SLC39A8 controls Mn homeostasis and epithelial integrity remain elusive. Here, we generate Slc39a8 intestinal epithelial cell-specific-knockout (Slc39a8-IEC KO) mice, which display markedly decreased Mn levels in blood and most organs. Radiotracer studies reveal impaired intestinal absorption of dietary Mn in Slc39a8-IEC KO mice. SLC39A8 is localized to the apical membrane and mediates 54Mn uptake in intestinal organoid monolayer cultures. Unbiased transcriptomic analysis identifies alkaline ceramidase 1 (ACER1), a key enzyme in sphingolipid metabolism, as a potential therapeutic target for SLC39A8-associated IBDs. Importantly, treatment with an ACER1 inhibitor attenuates colitis in Slc39a8-IEC KO mice by remedying barrier dysfunction. Our results highlight the essential roles of SLC39A8 in intestinal Mn absorption and epithelial integrity and offer a therapeutic target for IBD associated with impaired Mn homeostasis.

Associations between blood manganese levels and sarcopenia in adults: insights from the National Health and Nutrition Examination Survey.

While increasing concerns arise about the health effects of environmental pollutants, the relationship between blood manganese (Mn) and sarcopenia has yet to be fully explored in the general population. This study aims to investigate the association between blood manganese (Mn) levels and sarcopenia in adults. In our study, we evaluated 8,135 individuals aged 18-59 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018. We employed generalized additive model (GAM) to discern potential non-linear relationships and utilized the two-piecewise linear regression model to probe the association between blood Mn levels and sarcopenia. After adjusting for potential confounders, we identified non-linear association between blood Mn levels and sarcopenia, with an inflection point at 13.45 μg/L. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.006 (0.996 to 1.048) and 1.082 (1.043 to 1.122), respectively. Subgroup analysis showed that the effect sizes of blood Mn on sarcopenia have significant differences in gender and different BMI groups. Our results showed that a reverse U-shaped curve between blood Mn levels and sarcopenia, with an identified the inflection point at blood Mn level of 13.45 μg/L.

The non-linear associations between blood manganese level and sarcopenia in patients undergoing maintenance hemodialysis: A multicenter cross-sectional study

Background and aimsManganese (Mn), a vital element in energy metabolism, is predominantly stored in skeletal muscles and plays a crucial role in muscle function and strength. Patients on maintenance hemodialysis (MHD) often experience muscle wasting due to metabolic disruption and inflammation. This study aimed to explore the relationship between blood Mn levels and sarcopenia in a patient population. MethodsIn this multicenter cross-sectional study, conducted from March 2021 to March 2022, 386 patients on MHD from three medical centers were included. Blood Mn levels were measured using inductively coupled plasma mass spectrometry, and body composition was assessed post-dialysis using bioelectrical impedance analysis. Grip strength was measured using a digital dynamometer. The patients were categorized into groups with and without sarcopenia. Using a generalized additive model to fit a smooth curve, we employed a generalized linear model to identify the optimal inflection point and explore the threshold effect after discovering a segmented relationship. Subsequently, a binary logistic regression analysis was conducted to investigate the relationship between blood manganese levels and the risk of sarcopenia, with adjustments made for potential confounding factors. ResultsA negative correlation was observed between blood Mn levels and sarcopenia-related parameters (Appendicular Skeletal Muscle Mass Index and grip strength) in Spearman’s correlation analysis (both P < 0.05). After adjusting for confounding factors, a nonlinear association was identified. When blood Mn was ≤ 10.6 μg/L, the increase in sarcopenia was not statistically significant (P > 0.05). Conversely, when blood Mn exceeded 10.6 μg/L, each 1 μg/L increase raised the risk of sarcopenia by 0.1 times. Considering confounders, multivariate binary logistic regression confirmed an independent association between elevated blood Mn levels and sarcopenia. ConclusionThis study revealed an independent association between elevated blood Mn levels (> 10.6 μg/L) and sarcopenia in patients undergoing MHD. These findings emphasize the importance of understanding the Mn metabolism in the context of muscle health in this patient population. Further research is warranted to explore the underlying mechanisms and potential interventions for mitigating sarcopenia in patients with elevated blood Mn levels undergoing MHD.

Atypical case of hypermanganesemia with dystonia type 1: a treatable primary dystonia caused by inborn error of manganese metabolism

Dystonia is one of the most common movement disorders in the pediatric age group. Dystonia with hypermanganesemia have polycythemia with deranged iron profile, chronic liver disease and basal ganglia hyperintensity on T1 weighted MRI brain image as characteristic finding. We are reporting one case of dystonia, lower limb weakness, polycythemia, and characteristic basal ganglia hyperintensity with a normal iron profile without liver involvement which diagnosed as inherited manganese (Mn) transporter defect due to homozygous mutations of SLC30A10 gene. Most of the reported cases of this mutation have reported decreased iron profile in their blood report and liver involvement contrary to our case. Intravenous disodium calcium edetate chelation and oral iron therapy led to a decrease in whole blood Mn level as well as clinical improvement in the patient. This is a rare disorder and is one of the potentially treatable inherited metal storage disorders and fatal if left untreated.

Manganese and Sleep Outcomes in United States Adults: Results from the 2017–2020 National Health and Nutrition Examination Survey (NHANES)

BackgroundManganese (Mn) is an essential micronutrient, but inadequate or excess Mn intake can have a detrimental impact on human health. Despite the essentiality, little is known about the relationship between Mn and sleep. ObjectiveThis study aimed to examine the relationship between blood Mn concentrations and sleep outcomes in US adults. MethodsThis cross-sectional study used data on blood Mn and sleep from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) (n = 8356, age ≥18 y). Multivariable logistic regression was used to examine associations between quintiles of blood Mn concentrations and subjective sleep outcomes (short sleep duration, late sleep midpoint, trouble sleeping, and obstructive sleep apnea [OSA] symptoms), adjusting for age, gender, body mass index, race/ethnicity, income, smoking, inflammation-adjusted serum ferritin concentration (iron status), caffeine, and alcohol intake. Gender-stratified models were used due to interactions with gender. ResultsThe mean (SE) blood Mn concentration was 9.7 (0.1) μg/L in US adults. In males, a nonlinear association was noted in the relationship between blood Mn levels and short sleep duration on weekdays and weekends. The third Mn quintile (Q3) group had lower odds of short sleep duration (<7 h) on weekdays (odds ratio [OR]=0.6, 95% confidence interval [CI]: 0.4, 0.9) than the lowest Mn quintile (Q1, reference) after adjusting for covariates in males. The second Mn quintile (Q2) group had lower odds of late sleep midpoint on weekdays than Q1 (OR=0.6, 95% CI: 0.4, 0.8). In females, Q2 group had lower odds of OSA symptoms than Q1 (OR: 0.6, 95% CI: 0.4, 0.9). No relationship was noted between Mn and trouble sleeping. ConclusionsGender differences exist in the association between Mn and sleep in adults. Q1 group had the poorest sleep outcomes, including higher odds of short sleep duration (in males), late sleep midpoint (in males), and OSA symptoms (in females).

Detailed β-(1→3)-D-glucan and mannan antigen kinetics in patients with candidemia.

Fungal antigens such as β-(1→3)-D-glucan (BDG) or mannan (Mn) are useful for detection of candidemia. However, detailed data on serum levels before diagnosis and during treatment are scarce. We conducted a prospective study at two German tertiary care centers for 36 months. Sera from adult patients with candidemia were tested for BDG (Fungitell assay) and Mn (Platelia Candida Ag-Plus assay). For each patient, the clinical course and biomarker kinetics were closely followed and compared. 1,243 sera from 131 candidemia episodes and 15 relapses were tested. In 35% of episodes, empirical therapy included an antifungal drug. Before blood culture sampling, BDG and Mn levels were elevated in 62.4% and 30.8% of patients, respectively. Sensitivity at blood culture sampling was 78.6% (BDG) and 35.1% (Mn). BDG levels of non-survivors were significantly higher than those of survivors. During follow-up, a therapeutic response was associated with decreasing BDG and Mn levels in 84.3% or 70.5% of episodes, respectively. A median increase of 513 pg BDG/mL and 390 pg Mn/mL indicated a relapse of candidemia with a sensitivity of 80% or 46.7%, respectively. In 72.9% and 46.8% of patients, increasing BDG or Mn levels were associated with a fatal outcome. Prior to discharge, BDG and Mn levels had dropped or normalized in 65.7% or 82.1% of patients, respectively. Summarising, in patients with candidemia, biomarker positivity usually precedes culture positivity. Relapses are mostly accompanied by secondary biomarker increases. Rising concentrations of BDG and Mn predict lethality, whereas decreasing levels suggest a favorable outcome in the majority of patients.

Association of Blood Manganese and Preeclampsia: A Systematic Review and Meta-analysis.

A systematic review and meta-analysis was performed to comprehensively evaluate the association between manganese (Mn) level and preeclampsia (PE) during pregnancy. Relevant observational studies were retrieved by searching Medline, Web of Science, Embase, and Cochrane Library from database inception to May 25, 2023. Pooling results was performed using a random-effects model incorporating heterogeneity. This meta-analysis incorporated 18 observational studies, which included 1113 women with PE and 5480 normotensive pregnant women. Pooled results showed that compared to normotensive control, women with PE had significantly lower blood Mn concentration (standardized mean difference: -0.36, 95% confidence interval: -0.50 to -0.22, p < 0.001; I2 = 67%). Subgroup analysis showed that the results were not significantly affected by study country (African, Asian, or Western), timing of blood sampling (before, at, or after the diagnosis of PE), mean blood Mn level of controls, or numbers of confounding factors adjusted (p for subgroup analysis all > 0.05), while methods for measuring blood Mn levels might affect the results (p for subgroup difference < 0.001). Finally, pooled results of three studies showed that a high level of blood Mn was related to a low risk of PE with blood Mn analyzed in continuous (risk ratio [RR]: 0.71, 95% CI: 0.59 to 0.85, p < 0.001; I2 = 0%) and categorized variables (RR: 0.50, 95% CI: 0.30 to 0.82, p = 0.006; I2 = 32%). In conclusion, a low blood level of Mn may be associated with PE in pregnant women.

Independent and Combined Associations of Blood Manganese, Cadmium and Lead Exposures with the Systemic Immune-Inflammation Index in Adults.

Manganese (Mn), cadmium (Cd) and lead (Pb) have toxic effects on the immune system. However, their independent and combined effects on immune-inflammation responses are unclear. In recent years, the systemic immune-inflammation index (SII) has been developed as an integrated and novel inflammatory indicator. A retrospective cross-sectional study of 2174 adults ≥20 years old from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 was conducted. Generalized linear models were used to evaluate the independent and combined associations of SII with blood Mn, Cd and Pb levels. As continuous variables, both blood Cd and Mn showed dose-dependent relationships with the SII before and after adjusting for all potential confounding factors. Metal concentrations were then converted into categorical variables. Compared with the adults in the lowest Cd or Mn tertile, those in the highest tertile had higher risks of elevated SII. Furthermore, co-exposure to Mn and Cd also showed a positive relationship with the SII after adjusting for all confounding factors. However, the single effect of Pb exposure and the joint effect of Pb and other metal exposures on the SII were not observed. This study provides important epidemiological evidence of the associations of SII with single and co-exposure effects of blood Mn, Cd, and Pb.

Metal-ion transporter SLC39A8 is required for brain manganese uptake and accumulation

Manganese (Mn) is an essential nutrient, but is toxic in excess. Whole-body Mn levels are regulated in part by the metal-ion influx transporter SLC39A8, which plays an essential role in the liver by reclaiming Mn from bile. Physiological roles of SLC39A8 in Mn homeostasis in other tissues, however, remain largely unknown. To screen for extrahepatic requirements for SLC39A8 in tissue Mn homeostasis, we crossed Slc39a8-inducible global-KO (Slc39a8 iKO) mice with Slc39a14 KO mice, which display markedly elevated blood and tissue Mn levels. Tissues were then analyzed by inductively coupled plasma-mass spectrometry to determine levels of Mn. Although Slc39a14 KO; Slc39a8 iKO mice exhibited systemic hypermanganesemia and increased Mn loading in the bone and kidney due to Slc39a14 deficiency, we show Mn loading was markedly decreased in the brains of these animals, suggesting a role for SLC39A8 in brain Mn accumulation. Levels of other divalent metals in the brain were unaffected, indicating a specific effect of SLC39A8 on Mn. Invivo radiotracer studies using 54Mn in Slc39a8 iKO mice revealed that SLC39A8 is required for Mn uptake by the brain, but not most other tissues. Furthermore, decreased 54Mn uptake in the brains of Slc39a8 iKO mice was associated with efficient inactivation of Slc39a8 in isolated brain microvessels but not in isolated choroid plexus, suggesting SLC39A8 mediates brain Mn uptake via the blood-brain barrier. These findings establish SLC39A8 as a candidate therapeutic target for mitigating Mn uptake and accumulation in the brain, the primary organ of Mn toxicity.

0501 Manganese and sleep health outcomes in U.S. adults: analysis of the NHANES 2017-2020

Abstract Introduction Manganese (Mn) is an essential trace mineral required for normal growth and physiological processes. However, inadequate or excess Mn can have a detrimental impact on human health. Despite the essentiality, little is known about the relationship between Mn and sleep. The objective of this study is to examine the relationships between blood Mn levels and sleep patterns (duration, midpoint of sleep, obstructive sleep apnea [OSA] symptoms, and trouble sleeping) in U.S. adults. Methods Data from the 2017 to 2020 National Health and Nutrition Examination Survey (NHANES) was used for the analysis. Adults aged 18 or older with both blood Mn levels and sleep parameters were included (n=8356). Self-reported fall asleep time and wake up time in the past week were used to calculate sleep duration and midpoint. Trouble sleeping and symptoms of OSA were also collected. Blood Mn levels were divided into quintiles for analysis. Multivariable logistic regressions that accounted for complex study design were used. Results The mean (SE) blood Mn concentration was 9.7 (0.1) µg/L, and was higher among participants who were younger, female, identified as non-Hispanic Asian, had lower income, were non-smokers, and had lower iron levels (P&amp;lt; 0.05, for all). About 25% of adults had short sleep duration (&amp;lt; 7 hours) on weekdays. OSA symptoms were noted in 49% of adults. In men, the odds of short sleep duration on weekdays were higher among those with the lowest Mn level (Q1: &amp;lt; 7.0 µg/L) than the reference group (Q3: 8.5-10.0 µg/L) after adjusting for age, race, income, smoking, and iron (OR: 1.5, 95% CI: 1.1-2.1, P=0.03). Among women, Q2 (7.0-8.4 µg/L) was the related to the lowest odds of OSA symptoms compared to all other groups after adjusting for covariates (P=0.049). Conclusion Lower or higher Mn levels in blood were related to poor sleep health in U.S. adults, which suggests that inadequate or excessive Mn intake might be harmful to sleep. Future studies on the mechanisms of these relationships are needed. Support (if any) This work was supported by National Institutes of Health R01DK123022, R21NS112974 to YAS, and K01HL151673 to ECJ.

Possible Sources of Trace Metals in Obese Females Living in Informal Settlements near Industrial Sites around Gauteng, South Africa.

Trace metals have been reported in the literature to be associated with obesity. Exposure to some trace metals such as Mn, Cr, Ni, Cd, and Pb may pose a serious health risk to individuals living around a polluted environment. The present study assessed the levels of trace metals in the blood of obese females living around industrial areas in Gauteng, South Africa. The study was carried out using a mixed method approach. Only females with a BMI ≥ 30.0 were considered. A total of 120 obese females participated in the study (site 1: 40-industrial area, site 2: 40-industrial area, and site 3: 40-residential area), aged 18-45 and not in menopause. Blood samples were analysed for trace metals content using inductively coupled plasma mass spectrometry (ICP-MS). The mean concentrations of trace metals were in the order Pb > Mn > Cr > Co > As > Cd (site 1), Pb > Mn > Co > As > Cd (site 2), and Mn > Cr > Co > As > Pb > Cd (site 3). The blood Mn from site 1 ranged from 6.79 µg/L-33.99 µg/L, and the mean differences obtained from the participants from different sites were significant (p < 0.01). The blood levels of Mn, Pb, Cr, Co, As, and Cd were above the recommended limits set by the WHO in some of the participants. The present study noted, among others, closeness to industrial areas, lifestyle decisions such as the use of tobacco products by their partners indoors, and the method used for cooking as factors that might have accounted for the blood levels of Mn, Pb, Cd and Co. The study showed that there is a need for constant monitoring of the levels of trace metals in the blood of those living in these areas.

A novel homozygous SLC39A14 variant in an infant with hypermanganesemia and a review of the literature.

Manganese (Mn) is an essential trace metal necessary for good health; however, excessive amounts in the body are neurotoxic. To date, three genes (SLC30A10, SLC39A8, and SLC39A14) have been discovered to cause inborn errors in Mn metabolism in humans. As very rare diseases, the clinical features require further clarification. A male Chinese patient who mainly presented with hypermanganesemia and progressive parkinsonism-dystonia was recruited for this study. We collected and analyzed clinical information, performed whole-exome sequencing (WES), and reviewed the relevant literature. The motor-developmental milestones of the patient were delayed at the age of 4 months, followed by rapidly progressive dystonia. The patient displayed elevated Mn concentrations in blood and urine, and brain magnetic resonance imaging (MRI) showed symmetrical hyperintensity on T1-weighted images and hypointensity on T2-weighted images in multiple regions. A novel homozygous variant of the SLC39A14 gene (c.1058T > G, p.L353R) was identified. The patient was treated with disodium calcium edetate chelation (Na2CaEDTA). Three months later, mild improvement in clinical manifestation, blood Mn levels, and brain MRI was observed. To date, 15 patients from 10 families have been reported with homozygous mutations of SLC39A14, with a mean age of onset of 14.9 months. The common initial symptom is motor regression or developmental milestone delay, with a disease course for nearly all patients involving development of progressive generalized dystonia and loss of ambulation before treatment. Additionally, hypermanganesemia manifests as Mn values ranging from 4- to 25-fold higher than normal baseline levels, along with brain MRI results similar to those observed in the recruited patient. Nine SLC39A14 variants have been identified. Seven patients have been treated with Na2CaEDTA, and only one patient achieved obvious clinical improvement. We identified a novel SLC39A14 mutation related to autosomal recessive hypermanganesemia with dystonia-2, which is a very rare disease. Patients present motor regression or delay of developmental milestones and develop progressive generalized dystonia. Chelation therapy with Na2CaEDTA appears to effectively chelate Mn and increase urinary Mn excretion in some cases; however, clinical response varies. The outcome of the disease was unsatisfactory. This study expands the genetic spectrum of this disease.

Associations between welding fume exposure and neurological function in Japanese male welders and non-welders.

There are some studies reporting the association between (manganese [Mn]) exposure to welding fume and neurological dysfunction. This study examined the relationship between Mn exposure and neurological behavior in Japanese male welders and non-welders using biological samples, which to date has not been assessed in Japan. A total of 94 male welders and 95 male non-welders who worked in the same factories were recruited. The blood and urine samples were obtained from all the participants to measure Mn exposure levels. Neurological function tests were also conducted with all participants. The sampling of the breathing air zone using a personal sampler was measured for welders only. The odds ratios (ORs) for the Working Memory Index (WMI) scores were significantly higher among all participants in the low blood Mn concentration group than those in the high blood Mn concentration group (OR, 2.77; 95% confidence interval [CI], 1.24, 6.19; P=.013). The association of WMI scores and blood Mn levels in welders had the highest OR (OR, 3.73; 95% CI, 1.04, 13.38; P=.043). Although not statistically significant, a mild relationship between WMI scores and blood Mn levels was observed in non-welders (OR, 2.09; 95% CI, 0.63, 6.94; P=.227). The results revealed a significant positive relationship between blood Mn and neurological dysfunction in welders. Furthermore, non-welders at the same factories may be secondarily exposed to welding fumes. Further research is needed to clarify this possibility.

Welder's lung and brain MRI findings in manganese-exposed welders.

Biomarkers of manganese (Mn) exposure and manganism are poorly understood. Blood Mn levels are often used to assess exposure, while brain Mn accumulation may be demonstrated by pallidal hyperintensity at magnetic resonance imaging (MRI). Mn-containing electrodes used in manual metal arc welding may be associated with the welder's lungs. A cross-sectional study was set up to compare T1 intensity in basal ganglia at MRI and Mn blood levels in subjects with or without pneumoconiosis. Clinical, radiological, pulmonary function and laboratory parameters were assessed among 154 welders referred to our hospital for suspected pulmonary pathology. The study group included 123 male welders with pneumoconiosis (79.9%) and 31 welders without pulmonary damage (20.1%). The cases without pneumoconiosis were younger (38.5±6.6 vs 42.1±7.1, p=0.012). Cases with pneumoconiosis had blood lower Mn levels [13.5 (10-21)] as compared to those without pneumoconiosis [18.5 (7.8- 34)], p=0.035. In the same groups, the cases with high blood Mn levels were 49 (39.8%) and 18 (58.1%) p= 0.052, respectively. Brain MRI hyperintensity was found in 86 (55.8%) subjects with welder's lung 63 (51.2) but also in 23 (74.2) individuals without welder's lung. MRI hyperintensity in basal ganglia was significantly related to high blood Mn (p<0.005). This is the first study evaluating blood Mn levels of welders and their correlation with pulmonary and neurological effects. Poor working conditions may be associated with exposure to Mn and fibrogenic fumes leading to chronic lung diseases and hyperintensity in brain MRI suggesting Mn accumulation.

Insights into the health status of the general population living near an electroplating industry zone: metal elevations and renal impairment.

A cross-sectional study was conducted in 2016 in Zhejiang Province, China, to evaluate the body burdens of metals and metalloids associated with renal dysfunction in populations living near electroplating industries. We recruited 236 subjects and performed physical examinations, determined the blood and urinary levels of arsenic (As), cadmium (Cd), chromium (Cr), manganese (Mn), nickel (Ni), lead (Pb), antimony (Sb), and selenium (Se) by an inductively coupled plasma mass spectrometer (ICP-MS), and measured three renal impairment biomarkers, namely nacetyl-β-D-glucosaminidase (NAG), retinol-binding protein (RBP), and β2-microglobulin (BMG). The proportion of abnormal nasal symptoms in the exposure group (10.1%) was much higher than in the control group (0; p < 0.05). The blood and urinary levels of As, Cd, and Se in the exposure group were significantly higher than those in the control group (p < 0.05). The blood levels of Mn and Pb, as well as the urinary levels of Cr and Ni, were significantly higher in the exposure group than in the control group (p < 0.05). The exposure group demonstrated higher levels of NAG, RBP, and BMG than the control group (0.51 vs. 0.14mg/g creatinine, 12.79 vs. 9.26IU/g creatinine, and 1.39 vs. 0.78mg/g creatinine, respectively; p < 0.05). Urinary BMG was positively correlated with urinary Cd levels (r = 0.223, p < 0.05), while urinary RBP was correlated with blood Cd levels (r = 0.151, p < 0.05) and urinary Cd, Cr, Ni, and Se levels (r = 0.220, 0.303, 0.162, and 0.306, respectively; p < 0.05). In conclusion, our study indicated that a population living in the vicinity of electroplating industries had high body burdens of certain metals and metalloids associated with non-negligible renal dysfunction.

Association between blood manganese and bone mineral density in US adolescents.

Manganese (Mn) exposure may reduce bone mineral density (BMD); however, studies investigating its effects on BMD are limited, especially among adolescents. Therefore, the present study is aimed at investigating the association between blood Mn levels and BMD in adolescents. This cross-sectional study included participants aged 12-19years with National Health and Nutrition Examination Survey data collected between 2011 and 2018. Total, trunk bone, lumbar spine, and pelvic BMDs were used as outcome variables. Multivariate linear regression models were used to investigate the association between blood Mn levels and BMD. The relationship between blood Mn level and BMD was assessed using smooth curve fitting. In total, 1,703 participants (mean age 15.62 ± 2.31years) were considered. Multivariable linear regression models demonstrated that BMD decreased as blood Mn level increased, especially among girls aged 12-15years. This relationship was also observable in non-Hispanic whites and other races according to subgroup analyses stratified by race. Smooth curve fitting indicated the existence of a non-linear relationship between blood Mn and BMD after confounding variable adjustment. The present study indicated that blood Mn levels were negatively associated with BMD in adolescents, especially in girls aged 12-15years. Therefore, clinicians should be aware of the potential risk of low bone mass among adolescents with high blood Mn levels.

Association between Blood Manganese Levels and Visceral Adipose Tissue in the United States: A Population-Based Study.

Manganese (Mn) is an essential trace element with a narrow toxic margin for human health. The association between Mn exposure and adverse visceral adipose tissue (VAT) accumulation is unclear. This study aimed to estimate the associations of blood Mn levels with VAT mass or visceral obesity in the general population in the United States. This cross-sectional study included data of 7297 individuals released by National Health and Nutrition Examination Survey (NHANES). VAT was quantified with dual-energy X-ray absorptiometry, and blood Mn was measured using inductively coupled plasma mass spectrometry. The generalized linear model and generalized additive model (GAM) were applied to estimate the linear and non-linear associations between Mn levels and VAT mass, respectively. Logistic regression was used to estimate the associations between blood Mn levels and the risk of visceral obesity. Fully adjusted generalized linear regression revealed that individuals in the higher quantile of Mn had increased VAT mass compared with those in the lower quantile (β per quantile change = 0.025; 95% CI of 0.017, 0.033; p &lt; 0.001). Positive associations were also observed in males and females (males: β per quantile change = 0.012, 95% CI of 0.002, 0.022 (p = 0.020); female: β per quantile change = 0.036; 95% CI of 0.023, 0.048 (p &lt; 0.001)). The GAM illustrated that the non-linear associations between blood Mn levels and VAT mass were in U-shape patterns (effective degree of freedom &gt;1 in total participants, males, and females). A stratified analysis found significant interactions between Mn and the family income-to-poverty ratio (PIR) in males, with stronger associations in males with a PIR &lt; 1.3 (β = 0.109; 95% CI of 0.048, 0.170). Additional analyses revealed that individuals in the highest quantile of Mn had a 39% higher risk of visceral obesity (OR = 1.39; 95% CI of 1.15-1.69; p &lt; 0.001). Higher blood Mn levels were positively associated with increased VAT mass and visceral obesity risk. The adverse VAT phenotype associated with excessive blood Mn levels should be further investigated.