Blood Mn Research Articles

Prenatal metal concentrations and physical abnormalities in the Japan Environment and Children's Study.

The association between prenatal metal exposure and congenital anomalies is unclear. We aimed to examine the association between exposure to cadmium, lead, mercury, selenium, and manganese and physical abnormalities. Data from 89,887 pregnant women with singleton pregnancies who participated in the Japan Environment and Children's Study (JECS) were used. The correlation between maternal blood metal concentrations and physical abnormalities during the second or third trimester was investigated using logistic regression models. Physical anomalies included those observed at birth or at 1 month, primarily from ICD-10 Chapter 17, particularly congenital anomalies associated with environmental factors (e.g., hypospadias, cryptorchidism, cleft lip and palate, digestive tract atresia, congenital heart disease, and chromosomal abnormalities) and minor abnormalities. After adjusting for covariates, the OR (95% CIs) of physical abnormalities for a one-unit rise in Mn concentrations in all individuals were 1.26 (1.08, 1.48). The OR (95% CIs) of physical abnormalities in the 4th quartile (≥18.7 ng/g) were 1.06 (1.01, 1.13) (p-value for the trend = 0.034) compared with those in the 1st quartile (≤12.5 ng/g). In Japan, maternal blood Mn concentrations above threshold during pregnancy may slightly increase the incidence of physical abnormalities. Physical abnormalities (including minor anomalies and congenital anomalies) are associated with prenatal manganese concentrations. They are not associated with cadmium, lead, mercury, and selenium concentrations.

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.

Associations between blood essential metal mixture and serum uric acid: a cross-sectional study.

Although several studies have explored the associations between single essential metals and serum uric acid (SUA), the study about the essential metal mixture and the interactions of metals for hyperuricemia remains unclear. We performed a cross-sectional study to explore the association of the SUA levels with the blood essential metal mixture, including magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), zinc (Zn), manganese (Mn) in Chinese community-dwelling adults (n=1039). The multivariable linear regression, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were conducted to estimate the associations of blood essential metals with SUA levels and the BKMR model was also conducted to estimate the interactions of the essential metals on SUA. In the multivariable linear regression, the association of blood Mg, Mn, and Cu with SUA was statistically significant, both in considering multiple metals and a single metal. In WQS regression [β=13.59 (95%CI: 5.57, 21.60)] and BKMR models, a positive association was found between the mixture of essential metals in blood and SUA. Specifically, blood Mg and Cu showed a positive association with SUA, while blood Mn showed a negative association. Additionally, no interactions between individual metals on SUA were observed. In conclusion, further attention should be paid to the relationship between the mixture of essential metals in blood and SUA. However, more studies are needed to confirm these findings.

Blood Levels of Environmental Heavy Metals are Associated with Poorer Iron Status in Ugandan Children: A Cross-Sectional Study

BackgroundIron deficiency (ID) and environmental exposure to metals frequently co-occur among Ugandan children, but little is known about their associations, although iron and other divalent metals share the same intestinal absorption transporter, divalent metal transporter 1 (DMT1). ObjectivesWe examined associations between iron status and blood concentrations of lead, manganese (Mn), cobalt (Co), and cadmium, both singly and as a mixture. MethodsWe used data on sociodemographic status, iron biomarkers, and blood concentrations of heavy metals collected from a cross-sectional survey of 100 children aged 6–59 mo in Kampala, Uganda. We compared blood concentrations of metals in ID with iron-sufficient children. We examined associations between a metal mixture and iron biomarkers using multiple linear regression and weighted quintile sum regression. ResultsThe median (interquartile range) blood Mn (μg/L) was higher in ID children defined by soluble transferrin receptor (sTfR) and ferritin (ID compared with iron-sufficient children): (sTfR [21.3 {15.1, 28.8}, 11.2 {8.6, 18.5}], ferritin [19.5 {15.0, 27.2}, 11.2 {8.8, 19.6}]; P < 0.001 for both). Similarly, the median (interquartile range) blood Co (μg/L) was higher in ID children by ferritin ([0.5 {0.4, 0.9}, 0.4 {0.3, 0.5}], P = 0.05). Based on the multiple linear regression results, higher blood Co and Mn were associated with poorer iron status (defined by all 4 iron indicators for Co and by sTfR for Mn). The weighted quintile sum regression result showed that higher blood concentrations of a metal mixture were associated with poorer iron status represented by sTfR, ferritin, and hepcidin, mainly driven by Co and Mn. ConclusionsOur study findings suggest that poorer iron status is associated with overall heavy metal burden, predominantly Co and Mn, among Ugandan children. Further prospective studies should confirm our primary findings and investigate the combined effects of coexposures to neurotoxicants on the neurodevelopment of young children.

Prenatal manganese biomarkers and operant test battery performance in Mexican children: Effect modification by child sex

BackgroundManganese (Mn) is essential to healthy neurodevelopment, but both Mn deficiency and over-exposure have been linked to prefrontal cortex (PFC) impairments, the brain region that regulates cognitive and neurobehavioral processes responsible for spatial memory, learning, motivation, and time perception. These processes facilitated by attention, inhibitory control, working memory, and cognitive flexibility are often sexually dimorphic and complex, driven by multiple interconnected neurologic and cognitive domains. ObjectiveWe investigated the role of child sex as an effect modifier of the association between prenatal Mn exposure and performance in an operant testing battery (OTB) that assessed multiple cognitive and behavioral functional domains. MethodsChildren (N = 575) aged 6–8 years completed five OTB tasks. Blood and urinary Mn measurements were collected from mothers in the 2nd and 3rd trimesters. Multiple regression models estimated the association between Mn biomarkers at each trimester with OTB performance while adjusting for socio-demographic covariates. Covariate-adjusted weighted quantile sum (WQS) regression models were used to estimate the association of a Mn multi-media biomarker (MMB) mixture with OTB performance. Interaction terms were used to estimate modification effect by child sex. ResultsHigher blood Mn exposure was associated with better response rates (more motivation) on the progressive ratio task and higher overall accuracy on the delayed matching-to-sample task. In the WQS models, the MMB mixture was associated with better response rates (more motivation) on the progressive ratio task. Additionally, for the linear and WQS models, we observed a modification effect by child sex in the progressive ratio and delayed matching-to-sample tasks. Higher prenatal Mn biomarker levels were associated with improved task performance for girls and reduced performance in boys. ConclusionHigher prenatal blood Mn concentrations and the MMB mixture predicted improved performance on two of five operant tasks. Higher prenatal Mn concentrations regulated executive functions in children in a sexually dimorphic manner. Higher prenatal Mn exposure is associated with improved performance on spatial memory and motivation tasks in girls, suggesting that Mn's nutritional role is sexually dimorphic, and should be considered when making dietary and/or environmental intervention recommendations.

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.

Associations Between Individual and Combined Metal Exposures in Whole Blood and Kidney Function in U.S. Adults Aged 40 Years and Older.

The effects of metal exposure on kidney function have been reported in previous literature. There is limited and inconsistent information on the associations between individual and combined exposures to metals and kidney function among the middle-aged and older population.The aim of this study was to clarify the associations of exposure to individual metals with kidney function while accounting for potential coexposure to metal mixtures and to evaluate the joint and interactive associations of blood metals with kidney function.A total of 1669 adults aged 40 years and older were enrolled in the present cross-sectional study using the 2015-2016 National Health and Nutrition Examination Survey (NHANES). Single-metal and multimetal multivariable logistic regression models, quantile G-computation, and Bayesian kernel machine regression models (BKMR) were fitted to explore the individual and joint associations of whole blood metals [lead (Pb), cadmium (Cd), mercury (Hg), cobalt (Co), manganese (Mn), and selenium (Se)] with the odds of decreased estimated glomerular filtration rate (eGFR) and albuminuria. A decreased eGFR was defined as an eGFR ≤ 60 mL/min per 1.73 m2, and albuminuria was categorized as a urinary albumin-creatinine ratio (UACR) of ≥ 30.0 mg/g.The results from quantile G-computation and BKMR indicated positive associations between exposure to the metal mixture and the prevalence of decreased eGFR and albuminuria (all P values < 0.05). These positive associations were mainly driven by blood Co, Cd, and Pb. Furthermore, blood Mn was identified as an influential element contributing to an inverse correlation with kidney dysfunction within metal mixtures. Increasing blood Se levels were negatively associated with the prevalence of decreased eGFR and positively associated with albuminuria. In addition, a potential pairwise interaction between Mn-Co on decreased eGFR was identified by BKMR analysis.Findings from our study suggested a positive association between exposure to the whole blood metal mixture and decreased kidney function, with blood Co, Pb, and Cd being the main contributors to this association, while Mn demonstrated an inverse relationship with renal dysfunction. However, as our study was cross-sectional in nature, further prospective studies are warranted to better understand the individual and combined effects of metals on kidney function.

Sex-specific association between prenatal manganese exposure and working memory in school-aged children in Mexico city: An exploratory multi-media approach

It remains unclear whether manganese (Mn) exposure affects working memory (WM) in a sexually dimorphic manner. Further, no gold standard media exists to measure Mn, suggesting a combined blood and urinary Mn index may better capture the totality of exposure. We investigated the modification effect of child sex on the influence of prenatal Mn exposure on WM in school-age children, exploring two methodological frameworks to integrate exposure estimates across multiple exposure biomarkers. Leveraging the PROGRESS birth cohort in Mexico City, children (N = 559) ages 6–8 completed the between errors and strategy measures of the CANTAB Spatial Working Memory (SWM) task. Mn levels were assayed in blood and urine of mothers during the 2nd and 3rd trimesters and in umbilical cord blood from mothers and children at delivery. Weighted quantile sum regression estimated the association of a multi-media biomarker (MMB) mixture with SWM. We applied a confirmatory factor analysis to similarly quantify a latent blood Mn burden index. We then used an adjusted linear regression to estimate the Mn burden index with SWM measures. Interaction terms were used to estimate the modification effect by child sex for all models. Results showed that the between-errors-specific MMB mixture (i.e., this model demonstrates the impact of the MMB mixture on the between-error scores.) was associated (β = 6.50, 95% CI: 0.91, 12.08) with fewer between errors for boys and more between errors for girls. The strategy-specific MMB mixture (i.e., this model demonstrates the impact of the MMB mixture on the strategy scores) was associated (β = −1.36, 95% CI: 2.55, - 0.18) with less efficient strategy performance for boys and more efficient strategy performance for girls. A higher Mn burden index was associated (β = 0.86, 95% CI: 0.00, 1.72) with more between errors in the overall sample. The vulnerability to prenatal Mn biomarkers on SWM differs in the directionality by child sex. An MMB mixture and composite index of body burden are stronger predictors than a single biomarker for Mn exposure on WM performance.

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.

Blood metal/metalloid concentration of male subjects undergoing IVF/ICSI treatment outcomes: A prospective cohort study

BackgroundPrevious epidemiology studies reported that heavy metal/metalloid exposure is associated with the impairment of semen quality. However, it is still not clear whether the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment outcome will be affected after the heavy metal/metalloid exposure of the male partners. MethodsA prospective cohort study with a 2-year followed-up was conducted in a tertiary IVF center. A total of 111 couples undergoing IVF/ICSI treatment were initially recruited from November 2015 to November 2016. Male blood concentrations of heavy metal/metalloid including Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Mo, Cd, Hg, and Pb were measured by inductively coupled plasma mass spectrometry, and the lab and pregnancy outcome data were followed up. The associations between male blood heavy metal/metalloid concentration and the clinical outcomes were analyzed by Poisson regression analysis. ResultsOur results showed that none of the heavy metal/metalloid of male partners we investigated are significantly associated with the oocyte fertilization and good embryo (P ≥ 0.05); however, antral follicle count (AFC) was a protective factor for the oocyte fertilization (RR: 1.07, 95 % CI: 1.04–1.10). The blood Fe concentration of the male partner was positively associated (P < 0.05) with pregnancy in the first fresh cycle (RR:170.93, 95 % CI: 4.13–7082.04), cumulative pregnancy (RR: 23.61, 95 % CI: 3.25–171.64) and cumulative live birth (RR: 36.42, 95 % CI: 1.21–1092.54). In the first frozen embryo cycles, pregnancy was significantly associated (P < 0.05) with the blood Mn (RR: 0.01, 95 % CI:0.00–0.11) and Se concentration (RR: 0.01, 95 % CI:8.25 E-5–0.47) and female age (RR: 0.86, 95 % CI:0.75–0.99); live birth was significantly associated (P < 0.05) with the blood Mn concentration (RR: 0.00, 95 % CI: 1.14E-7–0.51). ConclusionsOur results suggested that the higher male blood Fe concentration was positively associated with pregnancy in the fresh embryo transfer cycle, cumulative pregnancy, and cumulative live birth, whereas the higher male blood Mn and Se concentration were associated with lower chance of pregnancy and live birth in the frozen embryo transfer cycle. However, the underline mechanism of this finding still needs further investigation.

Association between blood manganese levels and depressive symptoms among US adults: A nationally representative cross-sectional study

BackgroundRecent studies indicated that manganese (Mn) levels were inconsistently associated with the prevalence of depression. We aimed to evaluate whether blood Mn concentrations were associated with the risk of depression among US adults. MethodsUsing the NHANES 2011–2019 datasets, we conducted a cross-sectional study in 16,572 eligible participants with complete data on blood Mn concentrations and depression diagnosis. A weighted multivariable logistic model and restricted cubic spline model were applied to explore the association and dose-response relationship of blood Mn concentrations with depression risk in the total population and subgroups. ResultsIn the total population, compared with the lowest reference group of blood Mn, participants in the second, third, and fourth quartile had an OR of 0.84 (95%CI: 0.66, 1.07), 0.93 (95%CI: 0.73, 1.19) and 0.91 (95%CI: 0.71, 1.15) for depression (ptrend = 0.640). In subgroup analyses, doubling of blood Mn concentrations was associated with a 0.83-fold (95%CI: 0.67, 1.02), 0.30 -fold (0.14, 0.65) decreased risk of depression in females and other ethnic groups, respectively. Significant modification effects of ethnicity on the association of blood Mn concentrations with depression risk were observed. Limitationscross-sectional study design and self-reported depressive symptoms. ConclusionsElevated blood Mn concentrations were associated with decreased depression risk in females and other specific subgroups. Mn supplementation could be a potential pathway for intervention and prevention of depression.

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.

Influence of Environmental Exposure to Steel Waste on Endocrine Dysregulation and PER3 Gene Polymorphisms.

To evaluate the association between environmental exposure to the following chemical substances: cadmium (Cd), lead (Pb), nickel (Ni), manganese (Mn), benzene (BZN), and toluene (TLN), and Period Circadian Regulator 3 (PER3) gene variable number of tandem repeats (VNTR) polymorphisms, according to chronotype in a population living in a steel residue-contaminated area. This assessment comprises a study conducted from 2017 to 2019 with 159 participants who completed health, work, and Pittsburgh sleep scale questionnaires. Cd, Pb, Ni, Mn, BZN, and TLN concentrations in blood and urine were determined by Graphite Furnace Atomic Absorption Spectrometry (GFAAS) and Headspace Gas Chromatography (GC), and genotyping was carried out using Polymerase Chain Reaction (PCR). A total of 47% of the participants were afternoon chronotype, 42% were indifferent, and 11% were morning chronotype. Insomnia and excessive sleepiness were associated with the indifferent chronotype, while higher urinary manganese levels were associated with the morning chronotype (Kruskal-Wallis chi-square = 9.16; p < 0.01). In turn, the evening chronotype was associated with poorer sleep quality, higher lead levels in blood, and BZN and TLN levels in urine (χ2 = 11.20; p < 0.01) in non-occupationally exposed individuals (χ2 = 6.98; p < 0.01) as well as the highest BZN (χ2 = 9.66; p < 0.01) and TLN (χ2 = 5.71; p < 0.01) levels detected in residents from the influence zone 2 (far from the slag). Mn, Pb, benzene, and toluene contaminants may have influenced the different chronotypes found in the steel residue-exposed population.

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.

The effect of mask fit test on the association between the concentration of metals in biological samples and the results of time-weighted average personal exposure: A study on Japanese male welders.

The mask fit test confirms whether the wearing condition of the wearer's face and the facepiece of the respirators are used appropriately. This study aimed to examine whether the results of the mask fit test affect the association between the concentration of metals related to welding fumes in biological samples and the results of time-weighted average (TWA) personal exposures. A total of 94 male welders were recruited. Blood and urine samples were obtained from all participants to measure the metal exposure levels. Using personal exposure measurements, the 8-h TWA (8 h-TWA) of respirable dust, TWA of respirable Mn, and 8-h TWA of respirable Mn were calculated. The mask fit test was performed using the quantitative method specified in the Japanese Industrial Standard T8150:2021. Fifty-four participants (57%) passed the mask fit test. Only in the Fail group of the mask fit test, it was observed that blood Mn concentrations be positively associated with the results of TWA personal exposure after adjusting for multivariate factors (8-h TWA of respirable dust; coefficient, 0.066; standard error (SE), 0.028; P = 0.018, TWA of respirable Mn: coefficient, 0.048; SE, 0.020; P = 0.019, 8 h-TWA of respirable Mn: coefficient, 0.041; SE, 0.020; P = 0.041). The results clarify that welders with high concentrations of welding fumes in their breathing air zone are exposed to dust and Mn if there is leaking air owing to the lack of fitness between respirators and the wearer's face when using human samples in Japan.

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.

Bio substrate microelement concentrations in young men — residents of the Far North — under increased physical exercises

BACKGROUND: High-level athletic competitions necessitate more strenuous physical activity and this upsets the bodys chemistry balance. Numerous mechanisms are in place during sports to adapt to regular physical activity, but as a result, the body is progressively stressed out as it experiences a high loss in the bio-elements associated with intense exercise.&#x0D; AIM: to thoroughly analyze the chemical profiles of athletes residing in the city of Magadan, who have achieved great sporting success, and to identify the unique features of microelement concentrations in subjective samples (hair, whole blood).&#x0D; MATERIALS AND METHODS: The study was conducted to analyze elemental pictures of high-level athletes in the city of Magadan who were between the ages of 19 and 25 (n=29). Age-matched men who showed usual levels of physical activity comprise the control group (n=22). Different biological substrates (hair and whole blood, among others) were examined to determine the most informative substrate for the identification of the most common types of chronic elemental imbalance. This was considered particularly important for further prevention of typical region-related disorders in the body chemistry by increasing functional reserves. Eighteen macro- and microelements were examined via atomic emission and mass spectrometric methods with inductively coupled argon plasma.&#x0D; RESULTS AND DISCUSSION: The athletes examined in the present study exhibited higher levels of Ca, Co, Fe, Se, and Zn in their hair samples and showed higher median concentrations of blood Na and P, and an excess levels of blood Mn, when compared with the subjects who had moderate levels of physical activity and whose blood examination showed higher values of K, Mg, Co, Fe, Se, the deficiency of Co, Cu, Zn, and Fe, and excess of Mg and Se.&#x0D; CONCLUSION: However, data obtained in the present study did not enable us to explicitly draw inferences regarding sports-induced changes in the body microelement profile. In some cases, the elemental profile of athletes is similar to that of residents of Magadan and they show a typical northern type of deficiency in essential elements expressed in the hair. Notably, the frequency of hair deficits is frequently higher in young men who experience no increased exercise levels. Excessive toxic elements or heavy metals were not identified biological substrates examined in the present study. It was our understanding that long-term assessment of the athletes elemental imbalance which is formed under intense physical activity can be performed through spectral hair analysis. This is attributable to the fact that it is an accumulative bio substrate that shows no day-to-day fluctuations under changeable functional or psychoemotional states, as well as nutrition preferences.