[Show abstract][Hide abstract]ABSTRACT: Our objective is to evaluate the relationships between prenatal maternal stress and depressive symptoms, respectively, and infant neurodevelopment at 6 months, adjusted for heavy metals and oxidative stress. This research is a part of a multi-center birth cohort study in South Korea. Information on stress and depressive symptoms was collected during the first trimester using Psychosocial Well-Being Index Short Form (PWI-SF) and Center for Epidemiological Studies Depression Scale (CES-D). The Korean Bayley Scales of Infant Development-II assessment (BSID-II), which includes the standardized mental development index (MDI) and psychomotor developmental index (PDI), and Korean Ages & Stages Questionnaires (K-ASQ) were applied to infants at six months of age. A higher index score indicates better development. Among 641 babies, 320 were female (50%). Maternal PWI ≥ 29 (vs. PWI ≤ 18) during early pregnancy was associated with a decrease in MDI scores of 5.37 points (P = 0.02) after adjusting for socioeconomic factors. Maternal CES-D ≥ 26 (vs. CES-D ≤ 10) during early pregnancy was associated with a decrease in MDI scores of 8.18 points (P = 0.01). The associations remained significant even after adjustment for lead, cadmium, and MDA levels (P < 0.05). However, no association was found between maternal PWI/CES-D and PDI score. No interaction was observed between stress and lead exposure. We found an inverse association between prenatal maternal stress and depressive symptoms, and MDI scores in 6-month-old infants after adjustment for prenatal lead exposure, which is known to affect cognitive function negatively.
Full-text Article · Jun 2016 · Journal of Korean Medical Science
[Show abstract][Hide abstract]ABSTRACT: Chronic exposure to manganese (Mn) can lead to impairments in motor and cognitive functions. Several recent studies reported Mn-induced executive dysfunction. The present study compared the neural correlates of ongoing executive function of welders and healthy controls. Fifty-three welders and 44 healthy controls were enrolled. Participants were given functional magnetic resonance imaging (fMRI) scans and performed two modified versions of the Wisconsin Card Sorting Task (WCST) that differed in cognitive demand, and a task that established a high-level baseline (HLB) condition. Card Sorting Test and Word-Color Test were also used to assess executive performance. Neural activation of the bilateral superior-frontal cortex, right-inferior parietal cortex, and bilateral insula cortex were greater in healthy controls than in welders when contrasting the difficult version of the WCST with the HLB. There were also correlations between executive functions by the Card Sorting Test and Word-Color Test, and brain activation in the insula cortex using the WCST. Our results indicated that welders had altered neural processing related to executive function in the prefrontal cortex under conditions of high cognitive demand. Welders also had less activation of the insula cortex, a part of a larger network comprising the lateral prefrontal cortex and parietal cortex.
Full-text Article · May 2016 · Neurotoxicology and Teratology
[Show abstract][Hide abstract]ABSTRACT: We investigated the association between breastfeeding and cognitive development in infants during their first 3 years. The present study was a part of the Mothers' and Children's Environmental Health (MOCEH) study, which was a multi-center birth cohort project in Korea that began in 2006. A total of 697 infants were tested at age 12, 24, and 36 months using the Korean version of the Bayley Scales of Infant Development II (K-BSID-II). The use and duration of breastfeeding and formula feeding were measured. The relationship between breastfeeding and the mental development index (MDI) score was analyzed by multiple linear regression analysis. The results indicated a positive correlation between breastfeeding duration and MDI score. After adjusting for covariates, infants who were breastfed for ≥ 9 months had significantly better cognitive development than those who had not been breastfed. These results suggest that the longer duration of breastfeeding improves cognitive development in infants.
Full-text Article · Apr 2016 · Journal of Korean Medical Science
[Show abstract][Hide abstract]ABSTRACT: This study was conducted to estimate the cause-specific mortality in male emergency responders (ER), compare with that of Korean men. Mortality was also compared between more experienced firefighters (i.e., firefighters employed ≥20 years and firefighters employed ≥10 to <20 years) and less experienced firefighters and non-firefighters (i.e., firefighters employed <10 years and non-firefighters) to investigate associations between mortality and exposure to occupational hazards.
The cohort was comprised of 33,442 males who were employed as ERs between 1980 and 2007 and not deceased as of 1991. Work history was merged with the death registry from the National Statistical Office of Korea to follow-up on mortality between 1992 and 2007. Standardized mortality ratios (SMR) for ERs were calculated in reference to the Korean male population. Adjusted relative risks (ARRs) of mortalities for firefighters employed ≥20 years and ≥10 years to <20 years were calculated in reference to non-firefighters and firefighters employed < 10 years.
Overall (SMR=0.43, 95%CI=0.39-0.47) and some kinds of cause-specific mortalities were significantly lower among ERs compared with the Korean male population. No significant increase in mortality was observed across the major ICD-10 classifications among ERs. Mortality due to exposure to smoke, fire, and flames (SMR=3.11, 95% CI=1.87-4.85), however, was significantly increased among ERs. All-cause mortality (ARR=1.46, 95% CI=1.13-1.89), overall cancer mortality (ARR=1.54, 95% CI=1.02-2.31) and mortality of external injury, poisoning and external causes (ARR=3.13, 95% CI=1.80-5.46) were significantly increased among firefighters employed ≥20 years compared to those of non-firefighters and firefighters employed < 10 years.
An increase in mortality due to all cancer and external injury, poisoning, and external causes in firefighters employed ≥20 years compared with non-firefighters and firefighters employed <10 years suggests occupational exposure.
[Show abstract][Hide abstract]ABSTRACT: To investigate whether performance IQ in children is associated with maternal blood cadmium concentration in early pregnancy.Method
The present study is a component of the Mothers’ and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project in Korea that began in 2006. The study cohort consisted of 119 children whose mothers underwent testing of blood cadmium during early pregnancy. All children were evaluated using the Korean version of the Wechsler Preschool and Primary Scale of Intelligence, revised edition (WPPSI-R), at 60 months of age. Multivariate linear regression analysis was performed to analyze the correlation between IQ in children and maternal blood cadmium concentration in early pregnancy, after adjustment for covariates.ResultsMaternal blood cadmium concentration during early pregnancy was inversely associated with performance IQ, after adjustment for covariates such as sex, educational levels of both parents, family income, and maternal BMI. Maternal blood cadmium concentration, however, was not associated with cognitive IQ.Conclusion
Performance IQ in children is associated with maternal blood cadmium concentration in early pregnancy.
Full-text Article · Nov 2014 · Journal of Trace Elements in Medicine and Biology
[Show abstract][Hide abstract]ABSTRACT: An understanding of the characteristics of occupational lung cancer is important to establish policies that prevent carcinogen exposure and to compensate workers exposed to lung carcinogens. This study analyzed the characteristics of occupational lung cancers in workers who were compensated under the Industrial Accident Compensation Insurance Law between 1994 and 2011. A total of 179 occupational lung cancers were compensated. The main carcinogenic exposure was asbestos, followed by crystalline silica and hexavalent chromium. The mean exposure duration and latency were 19.8 and 23.2 yr. The most common industry was manufacturing, followed by construction and transportation. The most common occupation was maintenance and repair, followed by foundry work, welding, painting, and spinning or weaving. Although asbestos was predominant carcinogen, the proportion of these cases was relatively low compared to other developed countries. Proper surveillance system is needed to monitor occupational lung cancer and improve prevention measures.
Article · Nov 2014 · Journal of Korean Medical Science
[Show abstract][Hide abstract]ABSTRACT: Objective:
To investigate whether blood lead concentrations are elevated in iron-deficient children, and to examine the association between iron deficiency and/or elevated blood lead concentration and cognitive deficits in children.
The present study is a component of the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project in Korea that began in 2006. The study cohort consisted of 194 children who underwent testing of blood lead and serum C-reactive proteins (CRPs) and ferritin concentrations, and the Korean version of the Wechsler Preschool and Primary Scale of Intelligence, revised edition (WPPSI-R), at 60 months of age. In addition, the mothers' blood lead concentrations during pregnancy were included in the analyses. Multivariate linear regression analysis was performed to analyze the correlation between high blood lead and low serum ferritin concentrations, after adjustment for covariates, in children, as well as to analyze the association of verbal IQ with serum ferritin and blood lead concentrations.
Lead and ferritin concentrations were inversely and significantly associated in children after adjustment for covariates. Moreover, both concentrations were associated with verbal IQ, after adjustment for covariates, and each was associated with cognitive deficits after adjustment for the other. Sobel test statistics showed that blood lead concentration was a significant partial mediator for the relationship between iron deficiency and verbal IQ.
Due to the results discussed in the present study, cognitive deficit in children seems to be associated not only with iron deficiency, but also with blood lead concentration.
Article · Sep 2014 · Journal of Trace Elements in Medicine and Biology
[Show abstract][Hide abstract]ABSTRACT: Background
It is well known that lead exposure induces neurotoxic effects, which can result in a variety of neurocognitive dysfunction. Especially, occupational lead exposures in adults are associated with decreases in cognitive performance including working memory. Despite recent advances in human neuroimaging techniques, the neural correlates of lead-exposed cognitive impairment remain unclear. Therefore, this study was aimed to compare the neural activations in relation to working memory function between the lead-exposed subjects and healthy controls.
Thirty-one lead-exposed subjects and 34 healthy subjects performed an n-back memory task during MRI scan. We performed fMRI using the 1-back and 2-back memory tasks differing in cognitive demand. Functional MRI data were analyzed using within- and between-group analysis. We found that the lead-exposed subjects showed poorer working memory performance during high memory loading task than the healthy subjects. In addition, between-group analyses revealed that the lead-exposed subjects showed reduced activation in the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, pre supplementary motor areas, and inferior parietal cortex.
Our findings suggest that functional abnormalities in the frontoparietal working memory network might contribute to impairments in maintenance and manipulation of working memory in the lead-exposed subjects.
[Show abstract][Hide abstract]ABSTRACT: Background:
A great deal of research has been devoted to identifying subclinical functional brain abnormalities in manganese (Mn)-exposed welders. However, no previous study has investigated morphological brain abnormalities, such as changes in brain volume, in welders. This study evaluates morphological changes in brain volume among welders, and investigates the relationship between structural brain abnormalities and subclinical dysfunction in this population.
We used voxel-based morphometry (VBM) to assess differences in gray and white matter brain volumes between 40 welders with chronic Mn exposure and 26 age-matched control subjects. Correlation analyses were used to investigate the relationship between brain volume changes and decreased performance on neurobehavioral tests.
Brain volumes in the globus pallidus and cerebellar regions were significantly diminished in welders with chronic Mn exposure compared to controls (FDR-corrected P<0.05). These changes in brain volume were negatively correlated with cognitive performance and grooved pegboard scores.
There are measurable brain volume reductions in the globus pallidus and cerebellum of welders chronically exposed to Mn, and these volume reductions correlate with cognitive and motor neurobehavioral deficits. Our findings therefore indicate that volumetric measurement could be a useful subclinical marker among welders that show no signs of manganism.
[Show abstract][Hide abstract]ABSTRACT: Our objective was to evaluate the relationship between intrauterine exposure to cadmium and the presence of atopic dermatitis in infants 6 months of age, adjusted for covariates including exposure to other heavy metals. The present research is a component of the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project conducted in Korea. Study subjects were restricted to pregnant women in whom cadmium and lead levels were measured at delivery and whose infants were assessed for the presence of atopic disease at 6 months of age. The odds ratio (OR) for the presence of atopic dermatitis in 6-month-old infants whose cord blood had elevated cadmium levels, after adjustment for other covariates, was 2.350 (95% CI, 1.126-4.906). The OR for the presence of atopic dermatitis in infants whose cord blood had elevated lead levels was not significant. In the present study, the cord blood cadmium level was significantly associated with the presence of atopic dermatitis in 6-month-old infants; this was not true of the cord blood lead level. To the best of our knowledge, this is the first prospective study to show a relationship between prenatal exposure to cadmium and atopic dermatitis in infancy.
Full-text Article · Apr 2013 · Journal of Korean medical science
[Show abstract][Hide abstract]ABSTRACT: Chronic exposure to manganese (Mn), which can be an occupational hazard or can result from liver failure, is associated with adverse motor and cognitive outcomes. Evidence from previous neuroimaging and magnetic resonance spectroscopy studies suggested alteration of function in Mn-exposed brains. However, the effect of chronic exposure of the human brain to Mn on white matter (WM) structure has not yet been determined. In the present study, we used diffusion tensor imaging (DTI) to investigate whether welders exposed to Mn demonstrate differences in WM integrity, compared with control subjects. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on a voxel-wise basis in 30 male welders with exposure to Mn and in 19 age- and gender-matched control subjects. Direct comparison between welders and controls using investigator-independent Statistical Parametric Mapping (SPM) voxel-wise analysis of DTI metrics revealed a reduction of FA in the corpus callosum (CC) and frontal WM in Mn-exposed welders. Further, marked increases in RD and negligible changes in AD suggested that the microstructural changes in the CC and frontal WM result from compromised radial directionality of fibers in these areas, caused primarily by demyelination. Correlation analysis with neurobehavioral performance also suggested that the microstructural abnormalities were associated with subtle motor and cognitive differences in welders.
[Show abstract][Hide abstract]ABSTRACT: Chronic manganese (Mn) exposure often leads to impairments in fine motor and cognitive functions, particularly memory. However, the neural correlates of Mn-induced alterations in memory remain unclear. In the present study, we performed functional MRI (fMRI) with 2-back memory tests to assess the neural correlates of Mn-induced memory impairment in response to subclinical dysfunction in the working memory networks in welders exposed to Mn for extended periods of time. Within-group and between-group analyses revealed that brain activity in working memory networks was increased in welders with chronic Mn exposure during the 2-back verbal working memory task compared to healthy control individuals. Therefore, our fMRI findings indicate that welders might require more neural resources in working memory networks to compensate for subtle deficits in working memory and altered working memory processes, even if they performed the tasks at the same level as healthy control individuals.
[Show abstract][Hide abstract]ABSTRACT: In a previous study, regional delivery of manganese (Mn)ions within the brain revealed that the metal accumulates in the basal ganglia, where it induces degeneration of the globus pallidus. Degeneration of the basal ganglia impairs motor ability by compromising an important neural circuit involved in the regulation of motor control. Therefore, much research has been devoted to identifying a sensitive and non-invasive imaging marker to evaluate the functional correlates of Mn-related brain dysfunction.
We performed the first-ever sequential finger-tapping functional MRI (fMRI) experiment to investigate the behavioural significance of additionally recruited brain regions in welders with chronic Mn exposure.
During the finger tapping task, activation of the bilateral primary sensorimotor cortex (SM1), bilateral supplementary motor area (SMA), bilateral dorsolateral premotor cortex, bilateral superior parietal cortex and ipsilateral dentate nucleus was higher in the welding group (42 welders) than in the control group (26 controls). The pallidal index correlated with the activation observed in the contralateral SM1 for the finger tapping task of the left hand. The fMRI variables correlated with motor behaviour. Grooved Pegboard performances (right hand) correlated with activation, as seen in the ipsilateral and contralateral SMAs obtained during the finger tapping task of the right hand.
Our findings suggest that increased brain activation results from the compensational activation of ancillary cortical pathways, which ensures adequate motor function.
Article · Dec 2010 · Occupational and environmental medicine
[Show abstract][Hide abstract]ABSTRACT: This article presents a schematic review of the clinical manifestations of occupational neurologic disorders in Korea and discusses the toxicologic implications of these conditions. Vascular encephalopathy, parkinsonism, chronic toxic encephalopathy, cerebellar dysfunction, peripheral neuropathy, and neurodegenerative diseases are common presentations of occupational neurotoxic syndromes in Korea. Few neurotoxins cause patients to present with pathognomic neurologic syndrome. Detailed neurologic examinations and categorization of the clinical manifestations of neurologic disorders will improve the clinical management of occupational neurologic diseases. Physicians must be aware of the typical signs and symptoms of possible exposure to neurotoxins, and they should also pay attention to less-typical, rather-vague symptoms and signs in workers because the toxicologic characteristics of occupational neurologic diseases in Korea have changed from typical patterns to less-typical or equivocal patterns. This shift is likely to be due to several years of low-dose exposure, perhaps combined with the effects of aging, and new types of possibly toxicant-related neurodegenerative diseases. Close collaboration between neurologists and occupational physicians is needed to determine whether neurologic disorders are work-related.
Full-text Article · Jun 2010 · Journal of Clinical Neurology
[Show abstract][Hide abstract]ABSTRACT: To evaluate which T1-wieghted technique between 3D gradient-echo (FSPGR) and conventional spin-echo (SE) sequence is more sensitive predictor of neurobehavioral dysfunction found in welders with chronic manganese (Mn) acquired at 3 Tesla.
Forty-three current male welders and 29 age- and gender-matched, nonwelding production workers (control individuals) were recruited to the present study. Each subject underwent neurological examination, blood sample collection, and neurobehavioral tests, in addition to magnetic resonance imaging (MRI) examination. The MRI examinations were performed using a 3.0 Tesla whole-body scanner. T1-weighted axial images were obtained using SE and FSPGR with a 180 degrees inversion recovery prepared pulse, and the corresponding pallidal indices (PI), PI (SE), and PI (FSPGR), were calculated.
Both PI (SE) and PI (FSPGR) were well correlated with blood Mn level, but only PI (FSPGR) was significantly correlated with air Mn concentration (P = 0.007). Of the neurobehavioral performance indicators, after controlling for covariates, PI (FSPGR) was significantly associated with cognitive components, such as the digit symbol score, the digit span backward score, the Stroop test score and also with the grooved pegboard (dominant hand) score, whereas PI (SE) was associated only with grooved pegboard (dominant hand) score.
PI using a T1-weighted 3D FSPGR sequence shows the best correlation with neurobehavioral performance indicators and is the best measure for detection of blood and airborne Mn concentrations in welders exposed to excessive occupational Mn.
Full-text Article · Apr 2010 · Journal of Magnetic Resonance Imaging
[Show abstract][Hide abstract]ABSTRACT: Occupational and environmental exposure to manganese (Mn) is associated with various neurobehavioral and movement dysfunctions. However, few studies have systemically examined the neurochemical effects of Mn exposure.
We examined typical changes in cerebral metabolite ratios in welders chronically exposed to Mn, compared with control individuals, using proton magnetic resonance spectroscopy (MRS), investigated whether an abnormality in brain metabolism is associated with neurobehavioral changes, and assessed possible implications of chronic Mn exposure.
Thirty-five welders chronically exposed to Mn and 20 age-matched healthy subjects underwent single-voxel MRS at short echo time to assess the N-acetylaspartate (NAA), myoinositol (mI), total choline (tCho), and glutamine plus glutamate (Glx) levels, each of which was expressed as a ratio to total creatine (tCr). Neurobehavioral tests were also performed to define cognitive status.
NAA/tCr, Glx/tCr, and tCho/tCr ratios in the frontal gray matter (anterior cingulate cortex; ACC) and parietal white matter did not differ significantly between welders and control subjects. These metabolite ratios did not correlate significantly with blood Mn concentration or neurobehavioral parameters. However, mI levels in the ACC, but not in the parietal white matter, were significantly reduced in welders compared with control individuals (P<0.01). Furthermore, in the frontal lobe of the brain, the mI/tCr ratio was significantly correlated with verbal memory scores as well as blood Mn concentration (P<0.05).
The cognitive decline observed in welders exposed to Mn was associated with a decreased mI/tCr ratio in the ACC. The depletion of mI in welders may reflect possible glial cell swelling and/or detoxification processes associated with long-term exposure to Mn.
[Show abstract][Hide abstract]ABSTRACT: The aim of the study was to evaluate subclinical neurological effects in welders, using an extensive list of neurobehavioral batteries and determine if there is a link between pallidal index (PI) and subclinical neurobehavioral effects in the spectrum of manganese (Mn) symptomatology.
A total of 43 asymptomatic male welders and 29 age- and sex-matched healthy control individuals completed questionnaires, and underwent blood examinations, brain magnetic resonance imaging (MRI) scans, and a wide range of neurobehavioral examinations.
Digit symbol, auditory verbal learning test (delayed recall), complex figure test (copy and immediate recall), digit span, verbal fluency test, Stroop test, grooved pegboard, finger tapping, frequency dispersion and harmonic index of tremor, and maximum frequency of hand coordination showed differences between welders and control individuals. No differences were noted for simple reaction time, postural sway, smell test, and profile of mood states (POMS). Blood Mn levels were shown to be significantly associated with grooved pegboard (dominant hand) and complex figure test (copy) results. PI was significantly associated with digit symbol, digit span backward, Stroop Word and Stroop error index, and grooved pegboard (dominant hand) results.
The present findings that there were significant correlations between several neurobehavioral deficits and PI as well as blood Mn suggest that they may be attributed to Mn exposure in welding fumes. The present study also shows that PI is a better predictor of neurobehavioral performance than blood Mn levels in asymptomatic welders.
[Show abstract][Hide abstract]ABSTRACT: A 58-year-old woman was referred to our hospital due to progressive skin darkening, which began 5 months previously. The patient had strikingly diffuse blue-gray discoloration of the skin, most prominent in sun-exposed areas, especially her face and hands. The oral mucosa, tongue, gums, eye conjunctiva, ears, nail beds, and trunk were also involved. Bluish-gray discoloration of all nails was aggravated by cold weather. She had ingested 1 L of colloidal silver solution daily for approximately 16 months as a traditional remedy. Her serum silver concentration was 381 ng/ml which was a very high (reference level: <15 ng/ml). Light microscopic examination of a punch biopsy specimen from her nose revealed fine, minute, round, and brown-black granules deposited in the basement membrane of hair follicular epithelium. Scanning electron microscopic examination showed electron-dense granules deposited in the intercellular space of sweat glands. Energy disperse X-ray spectrometry analysis demonstrated peaks for silver and sulfur in the dense black deposits. The ingestion of colloidal silver appears to be an increasing practice among patients using alternative health practices. All silver-containing products including colloidal silver should be labeled with a clear warning to prevent argyria, especially in alternative health practices.
Article · Mar 2009 · American Journal of Industrial Medicine