Sample records for early mn exposure

  1. Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats.

    PubMed

    Beaudin, Stephane A; Strupp, Barbara J; Strawderman, Myla; Smith, Donald R

    2017-02-01

    Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1-21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230-237; http://dx.doi.org/10.1289/EHP258.

  2. Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats

    PubMed Central

    Beaudin, Stephane A.; Strupp, Barbara J.; Strawderman, Myla; Smith, Donald R.

    2016-01-01

    Background: Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. Objectives: To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. Methods: Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1–21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. Results: Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. Conclusions: This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230–237; http://dx.doi.org/10.1289/EHP258 PMID:27384154

  3. Pre-weaning Mn exposure leads to prolonged astrocyte activation and lasting effects on the dopaminergic system in adult male rats

    PubMed Central

    Kern, Cynthia; Smith, Donald R.

    2010-01-01

    Little is known about the effects of manganese (Mn) exposure over neurodevelopment and whether these early insults result in effects lasting into adulthood. To determine if early Mn exposure produces lasting neurobehavioral and neurochemical effects, we treated neonate rats with oral Mn (0, 25, or 50 mg Mn/kg/d over PND 1–21) and evaluated 1) behavioral performance in the open arena in the absence (PND 97) and presence (PND 98) of a d-amphetamine challenge, 2) brain dopamine D1 and D2-like receptors and dopamine transporter densities in the prefrontal cortex, striatum, and nucleus accumbens (PND 107), and 3) astrocyte marker glial fibrillary acidic protein (GFAP) levels in these same brain regions (PND 24 and 107). We found that pre-weaning Mn exposure did not alter locomotor activity or behavior disinhibition in adult rats, though Mn-exposed animals did exhibit an enhanced locomotor response to d-amphetamine challenge. Pre-weaning Mn exposure led to increased D1 and D2 receptor levels in the nucleus accumbens and prefrontal cortex, respectively, compared to controls. We also found increased GFAP expression in the prefrontal cortex in Mn-exposed PND 24 weanlings, and increased GFAP levels in prefrontal cortex, medial striatum and nucleus accumbens of adult (PND 107) rats exposed to pre-weaning Mn, indicating an effect of Mn exposure on astrogliosis that persisted and/or progressed to other brain regions in adult animals. These data show that pre-weaning Mn exposure leads to lasting molecular and functional impacts in multiple brain regions of adult animals, long after brain Mn levels returned to normal. PMID:20963817

  4. Effects from environmental Mn exposures: a review of the evidence from non-occupational exposure studies.

    PubMed

    Hudnell, H K

    1999-01-01

    The risk posed to human health by environmental manganese exposure is unknown. Occupational-exposure outcomes may not extrapolate to environmental exposures due to the healthy worker effect and differences in dosage parameters which may affect the biological response. This paper attempts to combine the existing literature on non-occupational Mn exposures with results from our current study in SW Quebec on environmental Mn exposure (Mergler et al., this issue) within the framework of a biologically-based, dose-response (BBDR) model. BBDR MODEL: The basic BBDR model consists of seven stages relating exposure to health effects. The stages are: 1) sources, 2) applied dose, 3) absorbed dose, 4) target-site dose, 5) toxic event, 6) measurable change, and 7) health outcome. Several air monitoring programs, such as the PTEAM study (Riverside, CA, 1990, mean PM10 Mn outdoor-airborne 24 h average = 0.045 microgram/m3), provided data relevant to the estimation of Mn applied dose, but did not include measures of body burden. Data from the SW Quebec study showed a mean total-particulate airborne Mn concentration of 0.022 microgram/m3 with a range of 0.009 to 0.035 microgram/m3 across four sampling sites, whereas the EPA reference concentration (RfC) is 0.05 microgram/m3. EPA has considered tap water levels to be safe below 200 micrograms/l Mn, and mean Mn tap-water (MnW) level in the participants' homes was 6.38 +/- 11.95 micrograms/l with a range from 0.1 to 158.9 micrograms/l Mn. A previous study of MnW exposure in Greece reported Mn levels in areas with low, medium and high MnW ranging from 4 to 2,300 micrograms/l and a significant association with Mn in hair but not Mn in blood (MnB). The mean absorbed dose of the SW Quebec study participants, as indicated by MnB, was 7.5 +/- 2.3 micrograms/l with a range of 2.5 to 15.9 micrograms/l. Our study and others on environmental Mn exposure did not provide an estimate of target-site dose. However, a significant correlation (r = 0

  5. Manganese in plasma: a promising biomarker of exposure to Mn in welders. A pilot study.

    PubMed

    Hoet, Perrine; Vanmarcke, Els; Geens, Tom; Deumer, Gladys; Haufroid, Vincent; Roels, Harry A

    2012-08-13

    There is raising concern about the potential neurotoxic effects of manganese (Mn) inhalation exposure in welders. Because most of the airborne particles in welding fume are in the respirable fraction, their bioavailability is likely to be higher than for coarser dust exposure. No well-validated biomarker for Mn exposure is available. To investigate the interest of measuring Mn in plasma (Mn-P) and urine (Mn-U) as biomarkers of exposure in a group of 28 welders whose tasks were only welding-related. Ambient air exposure to Mn (Mn-air) was determined by personal full-shift measurements on Monday and Tuesday. On the same days, blood and urine samples were collected before and after the shift. Mn-air varied from 1.3 to 729 μg/m(3) (GM 27.7). For Mn-U 65% of the values in welders were below the LOQ (0.20 μg/L). Compared to controls, the welders' Mn-P averaged 33% higher (1.5 vs 2.0 μg/L). In welders, the after-shift Mn-P values correlated well with Mn-air above 10 μg/m(3). In spite of similar Mn-air exposure on Monday and Tuesday, the relationships between Mn-air and after-shift Mn-P strikingly differed on Tuesday in that the inflection in the relationship was less obvious and the slope of the regression line (Mn-P after-shift/logMn-air) for a doubling of logMn-air was 2.3 times lower than on Monday. On Monday (the first day of the workweek), a Mn-P value of 2 μg/L could distinguish Mn-air exposure above or below 20 μg/m(3) with a sensitivity of 69% and a specificity of 82%. This preliminary study indicates that Mn-P is a promising biomarker of current exposure to Mn in welders and lends biological plausibility to the intended change for the Mn TLV-TWA of 20 μg/m(3) proposed by ACGIH for respirable Mn particulate. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Early Phthalates Exposure in Pregnant Women Is Associated with Alteration of Thyroid Hormones

    PubMed Central

    Tsai, Chih-Hsin; Liang, Wei-Yen; Li, Sih-Syuan; Huang, Han-Bin

    2016-01-01

    Introduction Previous studies revealed that phthalate exposure could alter thyroid hormones during the last trimester of pregnancy. However, thyroid hormones are crucial for fetal development during the first trimester. We aimed to clarify the effect of phthalate exposure on thyroid hormones during early pregnancy. Method We recruited 97 pregnant women who were offered an amniocentesis during the early trimester from an obstetrics clinic in southern Taiwan from 2013 to 2014. After signing an informed consent form, we collected amniotic fluid and urine samples from pregnant women to analyze 11 metabolites, including mono-ethyl phthalate (MEP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethylhexyl) phthalate (MEHP), mono-butyl phthalate (MnBP), of 9 phthalates using liquid chromatography/ tandem mass spectrometry. We collected blood samples from each subject to analyze serum thyroid hormones including thyroxine (T4), free T4, and thyroid-binding globulin (TBG). Results Three phthalate metabolites were discovered to be >80% in the urine samples of the pregnant women: MEP (88%), MnBP (81%) and MECPP (86%). Median MnBP and MECPP levels in pregnant Taiwanese women were 21.5 and 17.6 μg/g-creatinine, respectively, that decreased after the 2011 Taiwan DEHP scandal. Results of principal component analysis suggested two major sources (DEHP and other phthalates) of phthalates exposure in pregnant women. After adjusting for age, gestational age, TBG, urinary creatinine, and other phthalate metabolites, we found a significantly negative association between urinary MnBP levels and serum T4 (β = –5.41; p-value = 0.012; n = 97) in pregnant women using Bonferroni correction. Conclusion We observed a potential change in the thyroid hormones of pregnant women during early pregnancy after DnBP exposure. Additional study is necessitated to clarify these associations. PMID:27455052

  7. Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers.

    PubMed

    Modabbernia, A; Velthorst, E; Gennings, C; De Haan, L; Austin, C; Sutterland, A; Mollon, J; Frangou, S; Wright, R; Arora, M; Reichenberg, A

    2016-08-01

    Despite evidence for the effects of metals on neurodevelopment, the long-term effects on mental health remain unclear due to methodological limitations. Our objective was to determine the feasibility of studying metal exposure during critical neurodevelopmental periods and to explore the association between early-life metal exposure and adult schizophrenia. We analyzed childhood-shed teeth from nine individuals with schizophrenia and five healthy controls. We investigated the association between exposure to lead (Pb(2+)), manganese (Mn(2+)), cadmium (Cd(2+)), copper (Cu(2+)), magnesium (Mg(2+)), and zinc (Zn(2+)), and schizophrenia, psychotic experiences, and intelligence quotient (IQ). We reconstructed the dose and timing of early-life metal exposures using laser ablation inductively coupled plasma mass spectrometry. We found higher early-life Pb(2+) exposure among patients with schizophrenia than controls. The differences in log Mn(2+) and log Cu(2+) changed relatively linearly over time to postnatal negative values. There was a positive correlation between early-life Pb(2+) levels and psychotic experiences in adulthood. Moreover, we found a negative correlation between Pb(2+) levels and adult IQ. In our proof-of-concept study, using tooth-matrix biomarker that provides direct measurement of exposure in the fetus and newborn, we provide support for the role of metal exposure during critical neurodevelopmental periods in psychosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Exposure-response relationship and risk assessment for cognitive deficits in early welding-induced manganism.

    PubMed

    Park, Robert M; Bowler, Rosemarie M; Roels, Harry A

    2009-10-01

    The exposure-response relationship for manganese (Mn)-induced adverse nervous system effects is not well described. Symptoms and neuropsychological deficits associated with early manganism were previously reported for welders constructing bridge piers during 2003 to 2004. A reanalysis using improved exposure, work history information, and diverse exposure metrics is presented here. Ten neuropsychological performance measures were examined, including working memory index (WMI), verbal intelligence quotient, design fluency, Stroop color word test, Rey-Osterrieth Complex Figure, and Auditory Consonant Trigram tests. Mn blood levels and air sampling data in the form of both personal and area samples were available. The exposure metrics used were cumulative exposure to Mn, body burden assuming simple first-order kinetics for Mn elimination, and cumulative burden (effective dose). Benchmark doses were calculated. Burden with a half-life of about 150 days was the best predictor of blood Mn. WMI performance declined by 3.6 (normal = 100, SD = 15) for each 1.0 mg/m3 x mo exposure (P = 0.02, one tailed). At the group mean exposure metric (burden; half-life = 275 days), WMI performance was at the lowest 17th percentile of normal, and at the maximum observed metric, performance was at the lowest 2.5 percentiles. Four other outcomes also exhibited statistically significant associations (verbal intelligence quotient, verbal comprehension index, design fluency, Stroop color word test); no dose-rate effect was observed for three of the five outcomes. A risk assessment performed for the five stronger effects, choosing various percentiles of normal performance to represent impairment, identified benchmark doses for a 2-year exposure leading to 5% excess impairment prevalence in the range of 0.03 to 0.15 mg/m3, or 30 to 150 microg/m3, total Mn in air, levels that are far below those permitted by current occupational standards. More than one-third of workers would be impaired after

  9. Longitudinal T1 relaxation rate (R1) captures changes in short-term Mn exposure in welders

    PubMed Central

    Lewis, Mechelle M.; Flynn, Michael R.; Lee, Eun-Young; Van Buren, Scott; Van Buren, Eric; Du, Guangwei; Fry, Rebecca C.; Herring, Amy H.; Kong, Lan; Mailman, Richard B.; Huang, Xuemei

    2016-01-01

    Objectives We demonstrated recently that the T1 relaxation rate (R1) captured short-term Mn exposure in welders with chronic, relatively low exposure levels in a cross-sectional study. In the current study, we used a longitudinal design to examine whether R1 values reflect the short-term dynamics of Mn exposure. Methods Twenty-nine welders were evaluated at baseline and 12 months. Occupational questionnaires estimated short-term welding exposure using welding hours in the 90 days prior to each study visit (HrsW90). In addition, blood Mn levels, the pallidal index (PI; globus pallidus T1-weighted intensity (T1WI)/frontal white matter T1WI), and R1 values in brain regions of interest (ROIs) were determined as Mn biomarkers at each visit. Associations between changes in estimated welding exposure and changes in purported Mn biomarkers were assessed by Spearman’s correlations with adjustment for age and baseline R1, HrsW90, and blood Mn values. Results Changes in welding hours (HrsW90: the short-term welding exposure estimate), was associated significantly with changes in R1 values in the putamen (r=0.541, p=0.005), caudate (R=0.453, p=0.023), globus pallidus (R=0.430, p=0.032), amygdala (R=0.461, p=0.020), and hippocampus (R=0.447, p=0.025), but not with changes in blood Mn levels or the PI. Discussion Changes in R1 values correlated with changes in the short-term welding exposure estimate, but not with more traditional measures of Mn exposure (blood Mn levels or PI). These results suggest that R1 may serve as a useful marker to capture the short-term dynamics in Mn brain accumulation related to welding exposure. PMID:27567731

  10. Internal exposure to neutron-activated 56Mn dioxide powder in Wistar rats-Part 2: pathological effects.

    PubMed

    Shichijo, Kazuko; Fujimoto, Nariaki; Uzbekov, Darkhan; Kairkhanova, Ynkar; Saimova, Aisulu; Chaizhunusova, Nailya; Sayakenov, Nurlan; Shabdarbaeva, Dariya; Aukenov, Nurlan; Azimkhanov, Almas; Kolbayenkov, Alexander; Mussazhanova, Zhanna; Niino, Daisuke; Nakashima, Masahiro; Zhumadilov, Kassym; Stepanenko, Valeriy; Tomonaga, Masao; Rakhypbekov, Tolebay; Hoshi, Masaharu

    2017-03-01

    To fully understand the radiation effects of the atomic bombing of Hiroshima and Nagasaki among the survivors, radiation from neutron-induced radioisotopes in soil and other materials should be considered in addition to the initial radiation directly received from the bombs. This might be important for evaluating the radiation risks to the people who moved to these cities soon after the detonations and probably inhaled activated radioactive "dust." Manganese-56 is known to be one of the dominant radioisotopes produced in soil by neutrons. Due to its short physical half-life, 56 Mn emits residual radiation during the first hours after explosion. Hence, the biological effects of internal exposure of Wistar rats to 56 Mn were investigated in the present study. MnO 2 powder was activated by a neutron beam to produce radioactive 56 Mn. Rats were divided into four groups: those exposed to 56 Mn, to non-radioactive Mn, to 60 Co γ rays (2 Gy, whole body), and those not exposed to any additional radiation (control). On days 3, 14, and 60 after exposure, the animals were killed and major organs were dissected and subjected to histopathological analysis. As described in more detail by an accompanying publication, the highest internal radiation dose was observed in the digestive system of the rats, followed by the lungs. It was found that the number of mitotic cells increased in the small intestine on day 3 after 56 Mn and 60 Co exposure, and this change persisted only in 56 Mn-exposed animals. Lung tissue was severely damaged only by exposure to 56 Mn, despite a rather low radiation dose (less than 0.1 Gy). These data suggest that internal exposure to 56 Mn has a significant biological impact on the lungs and small intestine.

  11. Observations on the oxidation of Mn-modified Ni-base Haynes 230 alloy under SOFC exposure conditions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Z Gary; Xia, Gordon; Stevenson, Jeffry W.

    2005-07-01

    The commercial Ni-base Haynes 230 alloy (Ni-Cr-Mo-W-Mn) was modified with two increased levels of Mn (1 and 2 wt per cent) and evaluated for its oxidation resistance under simulated SOFC interconnect exposure conditions. Oxidation rate, oxide morphology, oxide conductivity and thermal expansion were measured and compared with commercial Haynes 230. It was observed that additions of higher levels of Mn to the bulk alloy facilitated the formation of a bi-layered oxide scale that was comprised of an outer M3O4 (M=Mn, Cr, Ni) spinel-rich layer at the oxide – gas interface over a Cr2O3-rich sub-layer at the metal – oxide interface.more » The modified alloys showed higher oxidation rates and the formation of thicker oxide scales compared to the base alloy. The formation of a spinel-rich top layer improved the scale conductivity, especially during the early stages of the oxidation, but the higher scale growth rate resulted in an increase in the area-specific electrical resistance over time. Due to their face-centered cubic crystal structure, both commercial and modified alloys demonstrated a coefficient of thermal expansion that was higher than that of typical anode-supported and electrolyte-supported SOFCs.« less

  12. Internal exposure to neutron-activated 56Mn dioxide powder in Wistar rats: part 1: dosimetry.

    PubMed

    Stepanenko, Valeriy; Rakhypbekov, Tolebay; Otani, Keiko; Endo, Satoru; Satoh, Kenichi; Kawano, Noriyuki; Shichijo, Kazuko; Nakashima, Masahiro; Takatsuji, Toshihiro; Sakaguchi, Aya; Kato, Hiroaki; Onda, Yuichi; Fujimoto, Nariaki; Toyoda, Shin; Sato, Hitoshi; Dyussupov, Altay; Chaizhunusova, Nailya; Sayakenov, Nurlan; Uzbekov, Darkhan; Saimova, Aisulu; Shabdarbaeva, Dariya; Skakov, Mazhin; Vurim, Alexandr; Gnyrya, Vyacheslav; Azimkhanov, Almas; Kolbayenkov, Alexander; Zhumadilov, Kasym; Kairikhanova, Yankar; Kaprin, Andrey; Galkin, Vsevolod; Ivanov, Sergey; Kolyzhenkov, Timofey; Petukhov, Aleksey; Yaskova, Elena; Belukha, Irina; Khailov, Artem; Skvortsov, Valeriy; Ivannikov, Alexander; Akhmedova, Umukusum; Bogacheva, Viktoria; Hoshi, Masaharu

    2017-03-01

    There were two sources of ionizing irradiation after the atomic bombings of Hiroshima and Nagasaki: (1) initial gamma-neutron irradiation at the moment of detonation and (2) residual radioactivity. Residual radioactivity consisted of two components: radioactive fallout containing fission products, including radioactive fissile materials from nuclear device, and neutron-activated radioisotopes from materials on the ground. The dosimetry systems DS86 and DS02 were mainly devoted to the assessment of initial radiation exposure to neutrons and gamma rays, while only brief considerations were given for the estimation of doses caused by residual radiation exposure. Currently, estimation of internal exposure of atomic bomb survivors due to dispersed radioactivity and neutron-activated radioisotopes from materials on the ground is a matter of some interest, in Japan. The main neutron-activated radionuclides in soil dust were 24 Na, 28 Al, 31 Si, 32 P, 38 Cl, 42 K, 45 Ca, 46 Sc, 56 Mn, 59 Fe, 60 Co, and 134 Cs. The radionuclide 56 Mn (T 1/2 = 2.58 h) is known as one of the dominant beta- and gamma emitters during the first few hours after neutron irradiation of soil and other materials on ground, dispersed in the form of dust after a nuclear explosion in the atmosphere. To investigate the peculiarities of biological effects of internal exposure to 56 Mn in comparison with external gamma irradiation, a dedicated experiment with Wistar rats exposed to neutron-activated 56 Mn dioxide powder was performed recently by Shichijo and coworkers. The dosimetry required for this experiment is described here. Assessment of internal radiation doses was performed on the basis of measured 56 Mn activity in the organs and tissues of the rats and of absorbed fractions of internal exposure to photons and electrons calculated with the MCNP-4C Monte Carlo using a mathematical rat phantom. The first results of this international multicenter study show that the internal irradiation due to

  13. Activation of MAPK and FoxO by Manganese (Mn) in Rat Neonatal Primary Astrocyte Cultures

    PubMed Central

    Exil, Vernat; Ping, Li; Yu, Yingchun; Chakraborty, Sudipta; Caito, Samuel W.; Wells, K. Sam; Karki, Pratap; Lee, Eunsook; Aschner, Michael

    2014-01-01

    Environmental exposure to manganese (Mn) leads to a neurodegenerative disease that has shared clinical characteristics with Parkinson's disease (PD). Mn-induced neurotoxicity is time- and dose-dependent, due in part to oxidative stress. We ascertained the molecular targets involved in Mn-induced neurodegeneration using astrocyte culture as: (1) Astrocytes are vital for information processing within the brain, (2) their redox potential is essential in mitigating reactive oxygen species (ROS) levels, and (3) they are targeted early in the course of Mn toxicity. We first tested protein levels of Mn superoxide dismutase -2 (SOD-2) and glutathione peroxidase (GPx-1) as surrogates of astrocytic oxidative stress response. We assessed levels of the forkhead winged-helix transcription factor O (FoxO) in response to Mn exposure. FoxO is highly regulated by the insulin-signaling pathway. FoxO mediates cellular responses to toxic stress and modulates adaptive responses. We hypothesized that FoxO is fundamental in mediating oxidative stress response upon Mn treatment, and may be a biomarker of Mn-induced neurodegeneration. Our results indicate that 100 or 500 µM of MnCl2 led to increased levels of FoxO (dephosphorylated and phosphorylated) compared with control cells (P<0.01). p-FoxO disappeared from the cytosol upon Mn exposure. Pre-treatment of cultured cells with (R)-(−)-2-oxothiazolidine-4-carboxylic acid (OTC), a cysteine analog rescued the cytosolic FoxO. At these concentrations, MAPK phosphorylation, in particular p38 and ERK, and PPAR gamma coactivator-1 (PGC-1) levels were increased, while AKT phosphorylation remained unchanged. FoxO phosphorylation level was markedly reduced with the use of SB203580 (a p38 MAPK inhibitor) and PD98059 (an ERK inhibitor). We conclude that FoxO phosphorylation after Mn exposure occurs in parallel with, and independent of the insulin-signaling pathway. FoxO levels and its translocation into the nucleus are part of early events

  14. AGE-RELATED, MULTIPLE-SYSTEM EFFECTS FROM ENVIRONMENTAL EXPOSURE TO AIRBORNE MANGANESE (MN)

    EPA Science Inventory

    Past research has tentatively associated excessive manganese (Mn) exposure with Parkinson-like effects in older adults, violent and aggressive behavior in young adults, and learning and neurobehavioral deficits in elementary school children. Our recent EPA/University of Quebec at...

  15. Manganese exposure and cognitive deficits: a growing concern for manganese neurotoxicity.

    PubMed

    Roels, H A; Bowler, R M; Kim, Y; Claus Henn, B; Mergler, D; Hoet, P; Gocheva, V V; Bellinger, D C; Wright, R O; Harris, M G; Chang, Y; Bouchard, M F; Riojas-Rodriguez, H; Menezes-Filho, J A; Téllez-Rojo, Martha Maria

    2012-08-01

    This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children's cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses.

    PubMed

    Claus Henn, Birgit; Austin, Christine; Coull, Brent A; Schnaas, Lourdes; Gennings, Chris; Horton, Megan K; Hernández-Ávila, Mauricio; Hu, Howard; Téllez-Rojo, Martha Maria; Wright, Robert O; Arora, Manish

    2018-02-01

    Associations between manganese (Mn) and neurodevelopment may depend on dose and exposure timing, but most studies cannot measure exposure variability over time well. We apply temporally informative tooth-matrix biomarkers to uncover windows of susceptibility in early life when Mn is associated with visual motor ability in childhood. We also explore effect modification by lead (Pb) and child sex. Participants were drawn from the ELEMENT (Early Life Exposures in MExico and NeuroToxicology) longitudinal birth cohort studies. We reconstructed dose and timing of prenatal and early postnatal Mn and Pb exposures for 138 children by analyzing deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry. Neurodevelopment was assessed between 6 and 16 years of age using the Wide Range Assessment of Visual Motor Abilities (WRAVMA). Mn associations with total WRAVMA scores and subscales were estimated with multivariable generalized additive mixed models. We examined Mn interactions with Pb and child sex in stratified models. Levels of dentine Mn were highest in the second trimester and declined steeply over the prenatal period, with a slower rate of decline after birth. Mn was positively associated with visual spatial and total WRAVMA scores in the second trimester, among children with lower (< median) tooth Pb levels: one standard deviation (SD) increase in ln-transformed dentine Mn at 150 days before birth was associated with a 0.15 [95% CI: 0.04, 0.26] SD increase in total score. This positive association was not observed at high Pb levels. In contrast to the prenatal period, significant negative associations were found in the postnatal period from ~ 6 to 12 months of age, among boys only: one SD increase in ln-transformed dentine Mn was associated with a 0.11 [95% CI: - 0.001, - 0.22] to 0.16 [95% CI: - 0.04, - 0.28] SD decrease in visual spatial score. Using tooth-matrix biomarkers with fine scale temporal profiles of exposure, we found discrete

  17. Early Life Exposures and Cancer

    Cancer.gov

    Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.

  18. A developmental perspective on early-life exposure to neurotoxicants.

    PubMed

    Bellinger, David C; Matthews-Bellinger, Julia A; Kordas, Katarzyna

    2016-09-01

    Studies of early-life neurotoxicant exposure have not been designed, analyzed, or interpreted in the context of a fully developmental perspective. The goal of this paper is to describe the key principles of a developmental perspective and to use examples from the literature to illustrate the relevance of these principles to early-life neurotoxicant exposures. Four principles are discussed: 1) the effects of early-life neurotoxicant exposure depend on a child's developmental context; 2) deficits caused by early-life exposure initiate developmental cascades that can lead to pathologies that differ from those observed initially; 3) early-life neurotoxicant exposure has intra-familial and intergenerational impacts; 4) the impacts of early-life neurotoxicant exposure influence a child's ability to respond to future insults. The first principle is supported by considerable evidence, but the other three have received much less attention. Incorporating a developmental perspective in studies of early-life neurotoxicant exposures requires prospective collection of data on a larger array of covariates than usually considered, using analytical approaches that acknowledge the transactional processes between a child and the environment and the phenomenon of developmental cascades. Consideration of early-life neurotoxicant exposure within a developmental perspective reveals that many issues remain to be explicated if we are to achieve a deep understanding of the societal health burden associated with early-life neurotoxicant exposures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Genetic and biochemical effects induced by iron ore, Fe and Mn exposure in tadpoles of the bullfrog Lithobates catesbeianus.

    PubMed

    Veronez, Alexandra Caroline da Silva; Salla, Rômulo Victor; Baroni, Vinícius Dadalto; Barcarolli, Indianara Fernanda; Bianchini, Adalto; Dos Reis Martinez, Claudia Bueno; Chippari-Gomes, Adriana Regina

    2016-05-01

    For decades, the extraction of minerals has intensified in order to meet the demand of industry. Iron ore deposits are important sources of metals, such as iron (Fe) and manganese (Mn). The particulate ores can be dispersed during extraction, transport and storage, with potential to induce biological impacts. Amphibians are very sensitive to environmental stressors. Therefore, the present study aimed to assess the effects of iron ore, Fe and Mn exposure during the metamorphosis of Lithobates catesbeianus. Endpoints analyzed included morphological (biometrical and developmental analyses), whole body Fe and Mn concentration in, plasma ferritin concentration, erythrocyte DNA damage (measured through comet assay and micronucleus test) and liver activity of enzymes involved in oxidative status [glutathione S-transferase (GST) and catalase (CAT)]. Tadpoles were kept under control condition (no contaminant addition) or exposed to iron ore (3.79mg/L as fine particulate matter); Fe (nominal concentration: 0.51mg/L Fe as C10H12FeN2NaO8; Fe-EDTA); and Mn (nominal concentration: 5.23mg/L Mn as 4H2O.MnCl2) for 30 days. Virtually, no mortality was observed, except for one tadpole found dead in the iron ore treatment. However, tadpoles exposed to iron ore had longer tail than those kept under control conditions while tadpoles exposed to manganese chloride showed higher body length than control ones. Exposure to Fe and Mn induced a delay in tadpole metamorphosis, especially when these metals are presented not as a mixture (iron ore). Tadpoles exposed to iron ore had increased whole body Fe and Mn while those exposed to Fe and Mn accumulated each metal individually. Tadpoles exposed to any of the contaminants tested showed a significant increase in erythrocyte DNA damage and frequency of micronuclei. In addition, they showed higher liver GST activity respect with those kept under control conditions. Plasma ferritin concentration and liver CAT activity were higher only in tadpoles

  20. In Vivo Manganese Exposure Modulates Erk, Akt and Darpp-32 in the Striatum of Developing Rats, and Impairs Their Motor Function

    PubMed Central

    Cordova, Fabiano M.; Aguiar, Aderbal S.; Peres, Tanara V.; Lopes, Mark W.; Gonçalves, Filipe M.; Remor, Aline P.; Lopes, Samantha C.; Pilati, Célso; Latini, Alexandra S.; Prediger, Rui D. S.; Erikson, Keith M.; Aschner, Michael; Leal, Rodrigo B.

    2012-01-01

    Manganese (Mn) is an essential metal for development and metabolism. However, exposures to high Mn levels may be toxic, especially to the central nervous system (CNS). Neurotoxicity is commonly due to occupational or environmental exposures leading to Mn accumulation in the basal ganglia and a Parkinsonian-like disorder. Younger individuals are more susceptible to Mn toxicity. Moreover, early exposure may represent a risk factor for the development of neurodegenerative diseases later in life. The present study was undertaken to investigate the developmental neurotoxicity in an in vivo model of immature rats exposed to Mn (5, 10 and 20 mg/kg; i.p.) from postnatal day 8 (PN8) to PN12. Neurochemical analysis was carried out on PN14. We focused on striatal alterations in intracellular signaling pathways, oxidative stress and cell death. Moreover, motor alterations as a result of early Mn exposure (PN8-12) were evaluated later in life at 3-, 4- and 5-weeks-of-age. Mn altered in a dose-dependent manner the activity of key cell signaling elements. Specifically, Mn increased the phosphorylation of DARPP-32-Thr-34, ERK1/2 and AKT. Additionally, Mn increased reactive oxygen species (ROS) production and caspase activity, and altered mitochondrial respiratory chain complexes I and II activities. Mn (10 and 20 mg/kg) also impaired motor coordination in the 3rd, 4th and 5th week of life. Trolox™, an antioxidant, reversed several of the Mn altered parameters, including the increased ROS production and ERK1/2 phosphorylation. However, Trolox™ failed to reverse the Mn (20 mg/kg)-induced increase in AKT phosphorylation and motor deficits. Additionally, Mn (20 mg/kg) decreased the distance, speed and grooming frequency in an open field test; Trolox™ blocked only the decrease of grooming frequency. Taken together, these results establish that short-term exposure to Mn during a specific developmental window (PN8-12) induces metabolic and neurochemical alterations in the striatum

  1. Assessing Susceptibility from Early-Life Exposure to Carcinogens

    PubMed Central

    Barton, Hugh A.; Cogliano, V. James; Flowers, Lynn; Valcovic, Larry; Setzer, R. Woodrow; Woodruff, Tracey J.

    2005-01-01

    Cancer risk assessment methods currently assume that children and adults are equally susceptible to exposure to chemicals. We reviewed available scientific literature to determine whether this was scientifically supported. We identified more than 50 chemicals causing cancer after perinatal exposure. Human data are extremely limited, with radiation exposures showing increased early susceptibility at some tumor sites. Twenty-seven rodent studies for 18 chemicals had sufficient data after postnatal and adult exposures to quantitatively estimate potential increased susceptibility from early-life exposure, calculated as the ratio of juvenile to adult cancer potencies for three study types: acute dosing, repeated dosing, and lifetime dosing. Twelve of the chemicals act through a mutagenic mode of action. For these, the geometric mean ratio was 11 for lifetime exposures and 8.7 for repeat exposures, with a ratio of 10 for these studies combined. The geometric mean ratio for acute studies is 1.5, which was influenced by tissue-specific results [geometric mean ratios for kidney, leukemia, liver, lymph, mammary, nerve, reticular tissue, thymic lymphoma, and uterus/vagina > 1 (range, 1.6–8.1); forestomach, harderian gland, ovaries, and thyroid < 1 (range, 0.033–0.45)]. Chemicals causing cancer through other modes of action indicate some increased susceptibility from postnatal exposure (geometric mean ratio is 3.4 for lifetime exposure, 2.2 for repeat exposure). Early exposures to compounds with endocrine activity sometimes produce different tumors after exposures at different ages. These analyses suggest increased susceptibility to cancer from early-life exposure, particularly for chemicals acting through a mutagenic mode of action. PMID:16140616

  2. Medical students' attitudes towards early clinical exposure in Iran.

    PubMed

    Khabaz Mafinejad, Mahboobeh; Mirzazadeh, Azim; Peiman, Soheil; Khajavirad, Nasim; Mirabdolhagh Hazaveh, Mojgan; Edalatifard, Maryam; Allameh, Seyed-Farshad; Naderi, Neda; Foroumandi, Morteza; Afshari, Ali; Asghari, Fariba

    2016-06-19

    This study was carried out to investigate the medical students' attitudes towards early clinical exposure at Tehran University of Medical Sciences. A cross-sectional study was conducted during 2012-2015. A convenience sample of 298 first- and second-year students, enrolled in the undergraduate medical curriculum, participated in an early clinical exposure program. To collect data from medical students, a questionnaire consisting of open-ended questions and structured questions, rated on a five-point Likert scale, was used to investigate students' attitudes toward early clinical exposure. Of the 298 medical students, 216 (72%) completed the questionnaires. The results demonstrated that medical students had a positive attitude toward early clinical exposure. Most students (80.1%) stated that early clinical exposure could familiarize them with the role of basic sciences knowledge in medicine and how to apply this knowledge in clinical settings. Moreover, 84.5% of them believed that early clinical exposure increased their interest in medicine and encouraged them to read more. Furthermore, content analysis of the students' responses uncovered three main themes of early clinical exposure, were considered helpful to improve learning: "integration of theory and practice", "interaction with others and professional development" and "desire and motivation for learning medicine". Medical students found their first experience with clinical setting valuable. Providing clinical exposure in the initial years of medical curricula and teaching the application of basic sciences knowledge in clinical practice can enhance students' understanding of the role they will play in the future as a physician.

  3. Manganese Exposure and Cognition Across the Lifespan: Contemporary Review and Argument for Biphasic Dose-Response Health Effects

    PubMed Central

    Vollet, Kaitlin; Dietrich, Kim N.

    2016-01-01

    Manganese (Mn) is both an essential micronutrient and potential neurotoxicant. This dual role underlies a growing body of literature demonstrating that Mn exhibits a biphasic dose-response relationship with neurocognitive outcomes. We reviewed recent epidemiologic studies from 2007–2016 that investigated the relationship between Mn exposure and cognitive outcomes across the lifespan: early life, school-aged children, and adulthood. In total, 27 research articles were included in this review: 12 pediatric and 15 adult studies (10 occupational and five environmental exposures). The majority of these studies provided evidence of the negative effects of Mn exposure on cognition. The pediatric literature provides evidence that both high and low levels of Mn are negatively associated with intellectual development. Future Mn research should include examination of non-linear relationships and multiple neurotoxicants across the lifespan, and particularly during critical developmental windows. PMID:27722879

  4. Medical students’ attitudes towards early clinical exposure in Iran

    PubMed Central

    Khabaz Mafinejad, Mahboobeh; Peiman, Soheil; Khajavirad, Nasim; Mirabdolhagh Hazaveh, Mojgan; Edalatifard, Maryam; Allameh, Seyed-Farshad; Naderi, Neda; Foroumandi, Morteza; Afshari, Ali; Asghari, Fariba

    2016-01-01

    Objectives This study was carried out to investigate the medical students’ attitudes towards early clinical exposure at Tehran University of Medical Sciences. Methods A cross-sectional study was conducted during 2012-2015. A convenience sample of 298 first- and second-year students, enrolled in the undergraduate medical curriculum, participated in an early clinical exposure program. To collect data from medical students, a questionnaire consisting of open-ended questions and structured questions, rated on a five-point Likert scale, was used to investigate students’ attitudes toward early clinical exposure. Results Of the 298 medical students, 216 (72%) completed the questionnaires. The results demonstrated that medical students had a positive attitude toward early clinical exposure. Most students (80.1%) stated that early clinical exposure could familiarize them with the role of basic sciences knowledge in medicine and how to apply this knowledge in clinical settings. Moreover, 84.5% of them believed that early clinical exposure increased their interest in medicine and encouraged them to read more. Furthermore, content analysis of the students’ responses uncovered three main themes of early clinical exposure, were considered helpful to improve learning: “integration of theory and practice”, “interaction with others and professional development” and “desire and motivation for learning medicine”. Conclusions Medical students found their first experience with clinical setting valuable. Providing clinical exposure in the initial years of medical curricula and teaching the application of basic sciences knowledge in clinical practice can enhance students’ understanding of the role they will play in the future as a physician. PMID:27318794

  5. Exposure to Potentially Traumatic Events in Early Childhood: Differential Links to Emergent Psychopathology

    ERIC Educational Resources Information Center

    Briggs-Gowan, Margaret J.; Carter, Alice S.; Clark, Roseanne; Augustyn, Marilyn; McCarthy, Kimberly J.; Ford, Julian D.

    2010-01-01

    Research NeedsObjective: To examine associations between exposure to potentially traumatic events (PTEs) and clinical patterns of symptoms and disorders in preschool children. Method: Two hundred and thirteen referred and non-referred children, ages 24 to 48 months (MN = 34.9, SD = 6.7 months) were studied. Lifetime exposure to PTEs (family…

  6. Trans-Agency Early-Life Exposures and Cancer Working Group

    Cancer.gov

    The Trans-Agency Early-Life Exposures and Cancer Working Group promotes integration of early-life events and exposures into public health cancer research, control, prevention, and policy strategies to reduce the cancer burden in the United States and globally.

  7. {sup 53}Mn-{sup 53}Cr CHRONOMETRY OF CB CHONDRITE: EVIDENCE FOR UNIFORM DISTRIBUTION OF {sup 53}Mn IN THE EARLY SOLAR SYSTEM

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yamashita, Katsuyuki; Yamakawa, Akane; Nakamura, Eizo

    High-precision Cr isotope ratios for chondrules and metal grain separated from CB chondrite Gujba were determined. The {epsilon}{sup 54}Cr values ({epsilon}{sup i}Cr = [({sup i}Cr/{sup 52}Cr){sub sample}/({sup i}Cr/{sup 52}Cr){sub standard} - 1] x 10{sup 4}) for all samples were identical within the analytical uncertainty, with a mean value of +1.29 {+-} 0.02. Uniform {epsilon}{sup 54}Cr signatures of both chondrules and metal grains imply that the Cr isotope systematics of the meteorite was once completely equilibrated. The {epsilon}{sup 53}Cr values of the chondrules and metal grain, on the other hand, display a strong correlation with the {sup 55}Mn/{sup 52}Cr ratio. Themore » {sup 53}Mn/{sup 55}Mn calculated from the slope of the isochron is (3.18 {+-} 0.52) x 10{sup -6}. This corresponds to absolute ages of 4563.7 {+-} 1.2 Ma and 4563.5 {+-} 1.1 Ma using angrites D'Orbigny and LEW 86010, respectively, as time anchors. These ages are consistent with the ages obtained using other short- and long-lived radio nuclides, supporting the uniform distribution of {sup 53}Mn in the early solar nebula.« less

  8. A historical overview of the development of manganese (Mn) ...

    EPA Pesticide Factsheets

    Abstract for Manganese 2016A historical overview of the development of manganese (Mn) pharmacokinetic data under Section 211(b) of the Clean Air Act (CAA)William K BoyesBackground. In the 1990’s, the use of methylcyclopentadienyl manganese tricarbonyl (MMT) as an octane-enhancing gasoline fuel additive led to concerns for potential public health consequences from exposure to Mn combustion products in automotive exhaust. Methods: After a series of regulatory / legal actions and negotiations, the EPA issued under CAA 211(b) an Alternative Tier 2 Test Rule that required development of scientific information intended to help resolve uncertainties in exposure or health risk estimates associated with MMT use. Among the uncertainties identified were: the chemical forms of Mn emitted in automotive exhaust; the relative toxicity of different Mn species; the potential for sensitive subpopulations including females, the young and elderly; differences in sensitivity between test species and humans; differences between inhalation and oral exposures; and the influence of dose rate and exposure duration on tissue accumulation of Mn. It was determined that development of specific sets of pharmacokinetic information and models regarding Mn could help resolve much of the uncertainties identified. Results. The results of the test program included development of several unique Mn PK datasets, and a series of increasingly sophisticated Mn physiologically-based pharmacokinetic

  9. Outdoor air pollution exposures and micronuclei frequencies in lymphocytes from pregnant women and newborns in Crete, Greece (Rhea cohort).

    PubMed

    O'Callaghan-Gordo, Cristina; Fthenou, Eleni; Pedersen, Marie; Espinosa, Ana; Chatzi, Leda; Beelen, Rob; Chalkiadaki, Georgia; Decordier, Ilse; Hoek, Gerard; Merlo, Domenico Franco; Nieuwenhuijsen, Mark; Roumeliotaki, Theano; Vafeiadi, Marina; Vande Loock, Kim; Kleinjans, Jos; Stephanou, Euripides; Kirsch-Volders, Micheline; Kogevinas, Manolis

    2015-11-01

    Micronuclei (MN) are biomarkers of early genetic effects that have been used to investigate the association between environmental exposures and cancer. However, few studies have examined the association between environmental exposures during pregnancy and MN in mothers and newborns. We examined MN frequency in maternal blood and in cord blood, in relation to maternal air pollution exposure, and the potential interaction with maternal vitamin C intake and maternal smoking. We used the cytokinesis-block micronucleus assay to assess MN frequency per 1000 bi-nucleated T-lymphocytes from 181 mothers and 183 newborns born in 2007-2008 in Heraklion (Crete, Greece). The ESCAPE land-use regression methods were used to estimate annual mean exposure to outdoor air pollution [particulate matter (PM), black carbon, nitrogen dioxide (NO2) and nitrogen oxides (NOx)] at maternal home addresses. Food frequency questionnaires were used to estimate maternal dietary vitamin C intake during pregnancy. Smoking habits were self-reported using questionnaires which were checked by measuring maternal urinary cotinine levels. Exposure to PM2.5 was associated with increased MN frequencies in pregnant women [rate ratio [RR (95%CI)] per 5 µg/m(3)=1.53 (1.02, 2.29)]. This increase was considerably higher among women who did not fulfill the recommended vitamin C dietary allowances [RR=9.35 (2.77, 31.61); n=20]. Exposure to PM2.5-10, PM10, NO2 and NOx were also associated with a higher incidence of MN frequencies in smoker women (n=56). No associations were found for newborns. We found an association between air pollution, particularly PM2.5, and MN frequency in mothers but not in newborns. This association was more pronounced among women with a lower dietary intake of vitamin C during pregnancy and among women who smoked during pregnancy. While results are clear in mothers, the association between maternal carcinogenic exposures during pregnancy and biomarkers of early biologic effect in the

  10. Neurotoxic effects of subchronic intratracheal Mn nanoparticle exposure alone and in combination with other welding fume metals in rats.

    PubMed

    Máté, Zsuzsanna; Horváth, Edina; Papp, András; Kovács, Krisztina; Tombácz, Etelka; Nesztor, Dániel; Szabó, Tamás; Szabó, Andrea; Paulik, Edit

    2017-04-01

    Manganese (Mn) is a toxic heavy metal exposing workers in various occupational settings and causing, among others, nervous system damage. Metal fumes of welding, a typical source of Mn exposure, contain a complex mixture of metal oxides partly in nanoparticle form. As toxic effects of complex substances cannot be sufficiently understood by examining its components separately, general toxicity and functional neurotoxicity of a main pathogenic welding fume metal, Mn, was examined alone and combined with iron (Fe) and chromium (Cr), also frequently found in fumes. Oxide nanoparticles of Mn, Mn + Fe, Mn + Cr and the triple combination were applied, in aqueous suspension, to the trachea of young adult Wistar rats for 4 weeks. The decrease of body weight gain during treatment, caused by Mn, was counteracted by Fe, but not Cr. At the end of treatment, spontaneous and evoked cortical electrical activity was recorded. Mn caused a shift to higher frequencies, and lengthened evoked potential latency, which were also strongly diminished by co-application of Fe only. The interaction of the metals seen in body weight gain and cortical activity were not related to the measured blood and brain metal levels. Fe might have initiated protective, e.g. antioxidant, mechanisms with a more general effect.

  11. Mn2+ exerts stronger structural effects than the Mn-citrate complex on the human erythrocyte membrane and molecular models.

    PubMed

    Suwalsky, M; Villena, F; Sotomayor, C P

    2010-01-01

    While traces of manganese (Mn) take part in important and essential functions in biology, elevated exposures have been shown to cause significant toxicity. Chronic exposure to the metal leads to manganese neurotoxicity (or manganism), a brain disorder that resembles Parkinsonism. Toxic effect mechanisms of Mn is not understood, toxic concentrations of manganese are not well defined and blood manganese concentration at which neurotoxicity occurs has not been identified. There are reports indicating that the most abundant Mn-species in Mn carriers within blood is the Mn-citrate complex. Despite the well-documented information about the toxic effects of Mn, there are scarce reports concerning the effects of manganese compounds on both structure and functions of cell membranes, particularly those of human erythrocytes. With the aim to better understand the molecular mechanisms of the interaction of Mn with cell membranes, MnCl(2), and the Mn-citrate complex were incubated with intact erythrocytes, isolated unsealead human erythrocyte membranes (IUM), and molecular models of the erythrocyte membrane. These consisted in bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes present in the outer and inner monolayers of the erythrocyte membrane, respectively. The capacity of the Mn compounds to perturb the bilayer structures of DMPC and DMPE was evaluated by X-ray diffraction, IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed by scanning electron microscopy (SEM). In all these systems it was found that Mn(2+) exerted considerable higher structural perturbations than the Mn-citrate complex.

  12. The OBELIX project: early life exposure to endocrine disruptors and obesity.

    PubMed

    Legler, Juliette; Hamers, Timo; van Eck van der Sluijs-van de Bor, Margot; Schoeters, Greet; van der Ven, Leo; Eggesbo, Merete; Koppe, Janna; Feinberg, Max; Trnovec, Tomas

    2011-12-01

    The hypothesis of whether early life exposure (both pre- and early postnatal) to endocrine-disrupting chemicals (EDCs) may be a risk factor for obesity and related metabolic diseases later in life will be tested in the European research project OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life). OBELIX is a 4-y project that started in May 2009 and which has the following 5 main objectives: 1) to assess early life exposure in humans to major classes of EDCs identified as potential inducers of obesity (ie, dioxin-like compounds, non-dioxin-like polychlorinated biphenyls, organochlorine pesticides, brominated flame retardants, phthalates, and perfluorinated compounds) by using mother-child cohorts from 4 European regions with different food-contaminant exposure patterns; 2) to relate early life exposure to EDCs with clinical markers, novel biomarkers, and health-effect data related to obesity; 3) to perform hazard characterization of early life exposure to EDCs for the development of obesity later in life by using a mouse model; 4) to determine mechanisms of action of obesogenic EDCs on developmental programming with in vivo and in vitro genomics and epigenetic analyses; and 5) to perform risk assessments of prenatal exposure to obesogenic EDCs in food by integrating maternal exposure through food-contaminant exposure and health-effect data in children and hazard data in animal studies.

  13. Pathways of inhalation exposure to manganese in children ...

    EPA Pesticide Factsheets

    Manganese (Mn) is both essential element and neurotoxicant. Exposure to Mn can occur from various sources and routes. Structural equation modeling was used to examine routes of exposure to Mn among children residing near a ferromanganese refinery in Marietta, Ohio. An inhalation pathway model to ambient air Mn was hypothesized. Data for model evaluation were obtained from participants in the Communities Actively Researching Exposure Study (CARES). These data were collected in 2009 and included levels of Mn in residential soil and dust, levels of Mn in children's hair, information on the amount of time the child spent outside, heat and air conditioning in the home and level of parent education. Hair Mn concentration was the primary endogenous variable used to assess the theoretical inhalation exposure pathways. The model indicated that household dust Mn was a significant contributor to child hair Mn (0.37). Annual ambient air Mn concentration (0.26), time children spent outside (0.24) and soil Mn (0.24) significantly contributed to the amount of Mn in household dust. These results provide a potential framework for understanding the inhalation exposure pathway for children exposed to ambient air Mn who live in proximity to an industrial emission source. The purpose of this study was to use a structural equations modeling approach combined with exposure estimates derived from air-dispersion modeling to assess potential inhalation exposure pathways for children to a

  14. Customized compact neutron activation analysis system to quantify manganese (Mn) in bone in vivo

    PubMed Central

    Liu, Yingzi; Mostafaei, Farshad; Sowers, Daniel; Hsieh, Mindy; Zheng, Wei; Nie, Linda H

    2018-01-01

    Objective In the US alone, millions of workers, including over 300 000 welders, are at high risk of occupational manganese (Mn) exposure. Those who have been chronically exposed to excessive amount of Mn can develop severe neurological disorders similar, but not identical, to the idiopathic Parkinson’s disease. One challenge of identifing the health effects of Mn exposure is to find a reliable biomarker for exposure assessment, especially for long-term cumulative exposure. Approach Mn’s long biological half-life as well as its relatively high concentration in bone makes bone Mn (BnMn) a potentially valuable biomarker for Mn exposure. Our group has been working on the development of a deuterium–deuterium (D–D)-based neutron generator to quantify Mn in bone in vivo. Main results and significance In this paper, we report the latest advancements in our system. With a customized hand irradiation assembly, a fully characterized high purity germanium (HPGe) detector system, and an acceptable hand dose of 36 mSv, a detection limit of 0.64 µg Mn/g bone (ppm) has been achieved. PMID:28060775

  15. Brain magnetic resonance imaging and manganese concentrations in red blood cells of smelting workers: Search for biomarkers of manganese exposure

    PubMed Central

    Jiang, Yueming; Zheng, Wei; Long, Liling; Zhao, Weijia; Li, Xiangrong; Mo, Xuean; Lu, Jipei; Fu, Xue; Li, Wenmei; Liu, Shouting; Long, Quanyong; Huang, Jinli; Pira, Enrico

    2014-01-01

    The MRI technique has been used in diagnosis of manganism in humans and non-human primates. This cross-sectional study was designed to explore whether the pallidal signal intensity in T1-weighted MRI correlated with Mn levels in the blood compartment among Mn-exposed workers and to understand to what extent the MRI signal could reflect Mn exposure. A group of 18 randomly selected male Mn-exposed workers of which 13 were smelting workers with high exposure (mean of airborne Mn in work place: 1.26 mg/m3; range: 0.31–2.93 mg/m3), and 5 power distribution control workers with low exposure (0.66 mg/m3 and 0.23–0.77 mg/m3) from a ferroalloy factory, and another group of 9 male subjects as controls from a non-smelting factory who were office or cafeteria workers (0.01 mg/m3 and 0–0.03 mg/m3) were recruited for neurological tests, MRI examination, and analysis of Mn in whole blood (MnB), plasma (MnP) or red blood cells (MnRBC). No clinical symptoms and signs of manganism were observed among these workers. MRI data showed average increases of 7.4% (p < 0.05) and 16.1% (p < 0.01) in pallidal index (PI) among low- and high-exposed workers, respectively, as compared to controls. Fourteen out of 18 Mn-exposed workers (78%) had intensified PI values, while this proportion was even higher (85%) among the high Mn-exposed workers. Among exposed workers, the PI values were significantly associated with MnRBC (r = 0.55, p = 0.02). Our data suggest that the workers exposed to airborne Mn, but without clinical symptoms, display an exposure-related, intensified MRI signal. The MRI, as well as MnRBC, may be useful in early diagnosis of Mn exposure. PMID:16978697

  16. Brain magnetic resonance imaging and manganese concentrations in red blood cells of smelting workers: search for biomarkers of manganese exposure.

    PubMed

    Jiang, Yueming; Zheng, Wei; Long, Liling; Zhao, Weijia; Li, Xiangrong; Mo, Xuean; Lu, Jipei; Fu, Xue; Li, Wenmei; Liu, Shouting; Long, Quanyong; Huang, Jinli; Pira, Enrico

    2007-01-01

    The MRI technique has been used in diagnosis of manganism in humans and non-human primates. This cross-sectional study was designed to explore whether the pallidal signal intensity in T1-weighted MRI correlated with Mn levels in the blood compartment among Mn-exposed workers and to understand to what extent the MRI signal could reflect Mn exposure. A group of 18 randomly selected male Mn-exposed workers of which 13 were smelting workers with high exposure (mean of airborne Mn in work place: 1.26 mg/m3; range: 0.31-2.93 mg/m3), and 5 power distribution control workers with low exposure (0.66 mg/m3 and 0.23-0.77 mg/m3) from a ferroalloy factory, and another group of 9 male subjects as controls from a non-smelting factory who were office or cafeteria workers (0.01 mg/m3 and 0-0.03 mg/m3) were recruited for neurological tests, MRI examination, and analysis of Mn in whole blood (MnB), plasma (MnP) or red blood cells (MnRBC). No clinical symptoms and signs of manganism were observed among these workers. MRI data showed average increases of 7.4% (p<0.05) and 16.1% (p<0.01) in pallidal index (PI) among low- and high-exposed workers, respectively, as compared to controls. Fourteen out of 18 Mn-exposed workers (78%) had intensified PI values, while this proportion was even higher (85%) among the high Mn-exposed workers. Among exposed workers, the PI values were significantly associated with MnRBC (r=0.55, p=0.02). Our data suggest that the workers exposed to airborne Mn, but without clinical symptoms, display an exposure-related, intensified MRI signal. The MRI, as well as MnRBC, may be useful in early diagnosis of Mn exposure.

  17. Hair Manganese as an Exposure Biomarker among Welders

    PubMed Central

    Reiss, Boris; Simpson, Christopher D.; Baker, Marissa G.; Stover, Bert; Sheppard, Lianne; Seixas, Noah S.

    2016-01-01

    Quantifying exposure and dose to manganese (Mn) containing airborne particles in welding fume presents many challenges. Common biological markers such as Mn in blood or Mn in urine have not proven to be practical biomarkers even in studies where positive associations were observed. However, hair Mn (MnH) as a biomarker has the advantage over blood and urine that it is less influenced by short-term variability of Mn exposure levels because of its slow growth rate. The objective of this study was to determine whether hair can be used as a biomarker for welders exposed to manganese. Hair samples (1cm) were collected from 47 welding school students and individual air Mn (MnA) exposures were measured for each subject. MnA levels for all days were estimated with a linear mixed model using welding type as a predictor. A 30-day time-weighted average MnA (MnA30d) exposure level was calculated for each hair sample. The association between MnH and MnA30d levels was then assessed. A linear relationship was observed between log-transformed MnA30d and log-transformed MnH. Doubling MnA30d exposure levels yields a 20% (95% confidence interval: 11–29%) increase in MnH. The association was similar for hair washed following two different wash procedures designed to remove external contamination. Hair shows promise as a biomarker for inhaled Mn exposure given the presence of a significant linear association between MnH and MnA30d levels. PMID:26409267

  18. Heterogeneity of Multimedia Exposures to Neurotoxic Elements (Al, As, Cd, Pb, Mn, and Hg) in Breastfed Infants from Porto Velho, Brazil.

    PubMed

    Bastos, Wanderley R; Vieira, Solange M; Manzatto, Ângelo G; Dórea, José G; Rubira, Marcelo C; de Souza, Victor Francisco P; da Costa Junior, Walkimar A; Souza Bastos, Maria T

    2017-10-01

    Infant exposure to neurotoxic elements is a public health issue that needs monitoring with regard to breast milk composition. We studied six neurotoxic elements in breast milk samples at different stages of lactation in mothers from Porto Velho, Brazil. We used a flow-injection mercury system (FIMS) to determine total Hg concentrations and an inductively coupled plasma optical emission spectrometer (ICP-OES) to determine the concentrations of Al, As, Cd, Pb, and Mn in 106 donors of a human milk bank. Association rules analyses were applied to determine the pattern of binary and ternary mixtures of the measured exposants. The metal concentration was mostly below the limit of detection (LOD) for Cd (99%), Pb (84%), and Hg (72%), and it was above the LOD for As (53%), Mn (60%), and Al (82%), respectively. Median concentrations (dry weight) of Al, As, Hg, Mn, and Pb were 1.81 μg/g, 13.8 ng/g, 7.1 ng/g, 51.1 ng/g, and 0.43 μg/g, respectively. Al is singly the most frequent element to which infants are exposed. Occurring binary combination (> LOD) was 56% for Al-Mn, 41% for Al-As, 22% for Al-Hg, and 13% for Al-Pb. In 100% of neonates, exposure to Al-ethylmercury (EtHg) occurred through immunization with thimerosal-containing vaccines (TCV). Association rules analysis revealed that Al was present in all of the multilevel combinations and hierarchical levels and that it showed a strong link with other neurotoxic elements (especially with Mn, As, and Hg). (a) Nursing infants are exposed to combinations of neurotoxicants by different routes, dosages, and at different stages of development; (b) In breastfed infants, the binary exposures to Al and total Hg can occur through breast milk and additionally through TCV (EtHg and Al); (c) The measured neurotoxic elements were found at low frequencies in breast milk and at concentrations that pose no public health concerns for milk banking.

  19. Hair Manganese as an Exposure Biomarker among Welders.

    PubMed

    Reiss, Boris; Simpson, Christopher D; Baker, Marissa G; Stover, Bert; Sheppard, Lianne; Seixas, Noah S

    2016-03-01

    Quantifying exposure and dose to manganese (Mn) containing airborne particles in welding fume presents many challenges. Common biological markers such as Mn in blood or Mn in urine have not proven to be practical biomarkers even in studies where positive associations were observed. However, hair Mn (MnH) as a biomarker has the advantage over blood and urine that it is less influenced by short-term variability of Mn exposure levels because of its slow growth rate. The objective of this study was to determine whether hair can be used as a biomarker for welders exposed to manganese. Hair samples (1cm) were collected from 47 welding school students and individual air Mn (MnA) exposures were measured for each subject. MnA levels for all days were estimated with a linear mixed model using welding type as a predictor. A 30-day time-weighted average MnA (MnA30d) exposure level was calculated for each hair sample. The association between MnH and MnA30d levels was then assessed. A linear relationship was observed between log-transformed MnA30d and log-transformed MnH. Doubling MnA30d exposure levels yields a 20% (95% confidence interval: 11-29%) increase in MnH. The association was similar for hair washed following two different wash procedures designed to remove external contamination. Hair shows promise as a biomarker for inhaled Mn exposure given the presence of a significant linear association between MnH and MnA30d levels. © The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  20. Using exposure windows to explore an elusive biomarker: blood manganese.

    PubMed

    Baker, Marissa G; Stover, Bert; Simpson, Christopher D; Sheppard, Lianne; Seixas, Noah S

    2016-05-01

    We sought to understand the time course between exposure to manganese (Mn) and uptake into the blood, to allow a more meaningful interpretation of exposure biomarker data, and to determine the utility of blood as a biomarker of Mn exposure. Welder trainees were monitored over the course of a five-quarter training program. Each quarter, trainees gave eight blood samples and had personal air monitoring four times. A mixed model was fit to obtain estimates of airborne exposure by welding type (fixed effect), adjusted for subject (random effect). Considering weekends and days absent as zero exposure, estimated exposures were summed over various exposure windows and related to measured blood manganese (MnB) using a mixed model. A relationship consistent with zero was found between MnB and modeled 1 or 7 days of exposure. After 30 days of preceding exposure, a 1 mg-days/m(3) increase in air Mn is associated with a 0.57 ng/mL increase in MnB (95% CI -0.04, 1.19). Considering a 90-day exposure window and a cumulative exposure window, a 1 mg-days/m(3) increase in air Mn is associated with a 0.26 (95% CI 0.005, 0.51) and 0.09 (95% CI 0.006, 0.17) ng/mL increase in MnB, respectively. From this analysis, MnB may begin to act as a biomarker of Mn exposure over longer time periods, or at higher levels of exposure. This novel study design allowed investigation of how MnB relates to different time windows of exposure, representing the most robust Mn exposure assessment in the biomarker literature.

  1. Parsing the Effects Violence Exposure in Early Childhood: Modeling Developmental Pathways

    PubMed Central

    Carter, Alice S.; Ford, Julian D.

    2012-01-01

    Objective To prospectively examine pathways from early childhood violence exposure and trauma-related symptoms to school-age emotional health. Methods A longitudinal, birth cohort (N = 437) was assessed with parent reports of lifetime violence exposure and trauma-related symptoms at 3 years of age and later, internalizing and externalizing symptoms, and social competence at school age. Results Early family and neighborhood violence correlated significantly with early trauma-related symptoms and also significantly predicted school-age internalizing and externalizing symptoms and poorer competence, independent of sociodemographic risk and past-year violence exposure. Longitudinal pathways were significantly mediated by arousal and avoidance symptoms at 3 years of age, which increased risk for clinically significant emotional problems and lower competence at school age (adjusted odds ratios = 3.1–6.1, p < 0.01). Conclusions Trauma-related symptoms may mediate developmental pathways from early violence exposure to later emotional health. Interventions that prevent or reduce early trauma-related symptoms may ameliorate the long-term deleterious impact of violence exposure. PMID:21903730

  2. Composition and origin of Early Cambrian Tiantaishan phosphorite-Mn carbonate ores, Shaanxi Province, China

    USGS Publications Warehouse

    Hein, J.R.; Fan, D.; Ye, J.; Liu, T.; Yeh, H.-W.

    1999-01-01

    The Tiantaishan phosphorite-Mn carbonate ores occur in the Early Cambrian Tananpo Formation in complexly folded and faulted rocks located in southern Shaanxi Province. About 65 x 106 tonnes of 17% P2O5 ore reserves exist and Mn-ore reserves are about 8.3 x 106 tonnes of +18% Mn. The stratigraphic sequence in ascending order consists of black phyllite, black to gray phosphorite ore, black phyllite, rhodochrostone ore, Mn mixed-carbonates, and dolostone. Data are presented from microprobe mineral chemistry, whole-rock chemistry, stable isotopes of carbonates, X-ray mineralogy, petrographic and SEM observations, and statistical analysis of chemical data. The dominant ore-forming minerals are hydroxy- and carbonate fluorapatite and Ca rhodochrosite, with Mg kutnahorite and dolomite comprising the Mn mixed-carbonate section. Pyrite occurs in all rock types and alabandite (MnS) occurs throughout the rhodochrostone section. The mean P2O5 content of phosphorite is 31% and argillaceous phosphorite is 16%, while the mean MnO content of rhodochrostone ore is 37%. Phosphorite ores are massive, spheroidal, laminated, and banded, while rhodochrostone ores have oolitic, spheroidal, and granular fabrics. The most distinguishing characteristics of the ores are high total organic carbon (TOC) contents (mean 8.4%) in the phosphorite and high P2O5 contents (mean 2.7%) in the rhodochrostone ore. The atypically high TOC contents in the Tiantaishan phosphorite probably result from very strong productivity leading to high sedimentation rates accompanied by weak reworking of sediments; poor utilization of the organic matter by bacteria; and/or partial replacement of bacterial or algal mats by the apatite. The depositional setting of the ores was the margin of an epicontinental seaway created as a direct consequence of global processes that included break-up of a supercontinent, formation of narrow seaways, creation of extensive continental shelves, overturn of stagnant, metal-rich deep

  3. The die is cast - Arsenic exposure in early life and disease susceptibility

    EPA Science Inventory

    Abstract Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for development and progression of disease in bo...

  4. Early Sign Language Exposure and Cochlear Implantation Benefits.

    PubMed

    Geers, Ann E; Mitchell, Christine M; Warner-Czyz, Andrea; Wang, Nae-Yuh; Eisenberg, Laurie S

    2017-07-01

    Most children with hearing loss who receive cochlear implants (CI) learn spoken language, and parents must choose early on whether to use sign language to accompany speech at home. We address whether parents' use of sign language before and after CI positively influences auditory-only speech recognition, speech intelligibility, spoken language, and reading outcomes. Three groups of children with CIs from a nationwide database who differed in the duration of early sign language exposure provided in their homes were compared in their progress through elementary grades. The groups did not differ in demographic, auditory, or linguistic characteristics before implantation. Children without early sign language exposure achieved better speech recognition skills over the first 3 years postimplant and exhibited a statistically significant advantage in spoken language and reading near the end of elementary grades over children exposed to sign language. Over 70% of children without sign language exposure achieved age-appropriate spoken language compared with only 39% of those exposed for 3 or more years. Early speech perception predicted speech intelligibility in middle elementary grades. Children without sign language exposure produced speech that was more intelligible (mean = 70%) than those exposed to sign language (mean = 51%). This study provides the most compelling support yet available in CI literature for the benefits of spoken language input for promoting verbal development in children implanted by 3 years of age. Contrary to earlier published assertions, there was no advantage to parents' use of sign language either before or after CI. Copyright © 2017 by the American Academy of Pediatrics.

  5. Early life exposures and the risk of adult glioma.

    PubMed

    Anic, Gabriella M; Madden, Melissa H; Sincich, Kelly; Thompson, Reid C; Nabors, L Burton; Olson, Jeffrey J; LaRocca, Renato V; Browning, James E; Pan, Edward; Egan, Kathleen M

    2013-09-01

    Exposure to common infections in early life may stimulate immune development and reduce the risk for developing cancer. Birth order and family size are proxies for the timing of exposure to childhood infections with several studies showing a reduced risk of glioma associated with a higher order of birth (and presumed younger age at infection). The aim of this study was to examine whether birth order, family size, and other early life exposures are associated with the risk of glioma in adults using data collected in a large clinic-based US case-control study including 889 glioma cases and 903 community controls. A structured interviewer-administered questionnaire was used to collect information on family structure, childhood exposures and other potential risk factors. Logistic regression was used to calculate odds ratios (OR) and corresponding 95% confidence intervals (CI) for the association between early life factors and glioma risk. Persons having any siblings were at significantly lower risk for glioma when compared to those reporting no siblings (OR=0.64; 95% CI 0.44-0.93; p=0.020). Compared to first-borns, individuals with older siblings had a significantly lower risk (OR=0.75; 95% CI 0.61-0.91; p=0.004). Birth weight, having been breast fed in infancy, and season of birth were not associated with glioma risk. The current findings lend further support to a growing body of evidence that early exposure to childhood infections reduces the risk of glioma onset in children and adults.

  6. Median infectious dose (ID₅₀) of porcine reproductive and respiratory syndrome virus isolate MN-184 via aerosol exposure.

    PubMed

    Cutler, Timothy D; Wang, Chong; Hoff, Steven J; Kittawornrat, Apisit; Zimmerman, Jeffrey J

    2011-08-05

    The median infectious dose (ID(50)) of porcine reproductive and respiratory syndrome (PRRS) virus isolate MN-184 was determined for aerosol exposure. In 7 replicates, 3-week-old pigs (n=58) respired 10l of airborne PRRS virus from a dynamic aerosol toroid (DAT) maintained at -4°C. Thereafter, pigs were housed in isolation and monitored for evidence of infection. Infection occurred at virus concentrations too low to quantify by microinfectivity assays. Therefore, exposure dose was determined using two indirect methods ("calculated" and "theoretical"). "Calculated" virus dose was derived from the concentration of rhodamine B monitored over the exposure sequence. "Theoretical" virus dose was based on the continuous stirred-tank reactor model. The ID(50) estimate was modeled on the proportion of pigs that became infected using the probit and logit link functions for both "calculated" and "theoretical" exposure doses. Based on "calculated" doses, the probit and logit ID(50) estimates were 1 × 10(-0.13)TCID(50) and 1 × 10(-0.14)TCID(50), respectively. Based on "theoretical" doses, the probit and logit ID(50) were 1 × 10(0.26)TCID(50) and 1 × 10(0.24)TCID(50), respectively. For each point estimate, the 95% confidence interval included the other three point estimates. The results indicated that MN-184 was far more infectious than PRRS virus isolate VR-2332, the only other PRRS virus isolate for which ID(50) has been estimated for airborne exposure. Since aerosol ID(50) estimates are available for only these two isolates, it is uncertain whether one or both of these isolates represent the normal range of PRRS virus infectivity by this route. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. African ancestry, early life exposures, and respiratory morbidity in early childhood.

    PubMed

    Kumar, R; Tsai, H-J; Hong, X; Gignoux, C; Pearson, C; Ortiz, K; Fu, M; Pongracic, J A; Burchard, E G; Bauchner, H; Wang, X

    2012-02-01

    Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02-1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19-1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14-1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05-1.34) and European ancestry (OR: 0.84, 95% CI: 0.74-0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (OR(whites) : 0.31, 95% CI: 0.09-1.14; OR(hispanic) : 0.47, 95% CI: 0.20-1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to evaluate wheezing disparities and a proxy for differentially distributed genetic and

  8. African ancestry, early life exposures, and respiratory morbidity in early childhood

    PubMed Central

    Kumar, R.; Tsai, H.-J.; Hong, X.; Gignoux, C.; Pearson, C.; Ortiz, K.; Fu, M.; Pongracic, J. A.; Burchard, E. G.; Bauchner, H.; Wang, X.

    2012-01-01

    Summary Background Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. Objective To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. Methods We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Results Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02–1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19–1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14–1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05–1.34) and European ancestry (OR: 0.84, 95% CI: 0.74–0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (ORwhites: 0.31, 95% CI: 0.09–1.14; ORhispanic: 0.47, 95% CI: 0.20–1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. Conclusions and Clinical Relevance In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to

  9. Neuropsychological Effects of Low-Level Manganese Exposure in Welders

    PubMed Central

    Laohaudomchok, Wisanti; Lin, Xihong; Herrick, Robert F.; Fang, Shona C.; Cavallari, Jennifer M.; Shrairman, Ruth; Landau, Alexander; Christiani, David C.; Weisskopf, Marc G.

    2011-01-01

    While the neuropsychological effects of high manganese (Mn) exposure in occupational settings are well known, the effects of lower levels of exposure are less understood. In this study, we investigated the neuropsychological effects of lower level occupational Mn exposure in 46 male welders (mean age = 37.4, sd = 11.7 years). Each welders’ cumulative Mn exposure indices (Mn-CEI) for the past 12 months and total work history Mn exposure were constructed based on air Mn measurements and work histories. The association between these exposure indices and performance on cognitive, motor control, and psychological tests was examined. In addition, among a subset of welders (n=24) who completed the tests both before and after a work shift, we examined the association between cross-shift Mn exposure assessed from personal monitoring and acute changes in test scores. Mn exposures in this study (median = 12.9 μg/m3) were much lower, as compared to those observed in other similar studies. Increasing total Mn-CEI was significantly associated with slower reaction time on the continuous performance test (CPT; p<0.01), as well as worse mood for several scales on the Profile of Mood States (POMS; confused, tired, and a composite of tired and energetic, all p≤0.03). Increasing Mn-CEI over the previous 12 months was significantly associated with worse mood on the sad, tense, and confused POMS scales (all p≤0.03) and the association with worse CPT performance approached significance (p=0.10). Higher Mn exposure over the course of a workday was associated with worse performance on the CPT test across the day (p=0.06) as well as declines in fine motor control over the work-shift (p=0.04), adjusting for age and time between the 2 tests. Our study suggests that even at relatively low Mn exposure levels neuropsychological effects may manifest particularly with respect to attention, mood, and fine motor control. PMID:21192973

  10. Early exposure to media violence and later child adjustment.

    PubMed

    Fitzpatrick, Caroline; Barnett, Tracie; Pagani, Linda S

    2012-05-01

    The extent to which early childhood exposure to violent media is associated with subsequent adverse child functioning remains disconcerting. In this study, we examine whether preschool child exposure to what parents generally characterize as violent television programming predicts a range of second-grade mental health outcomes. Participants are from the Quebec Longitudinal Study of Child Development (N = 1786). At 41 and 53 months, parents reported whether the child had viewed television shows and videos consisting of what they judged as violent content. According to parents, children watched on average 1.8 hours of mixed programming per day. Parent-reported child exposure to televised violence was associated with teacher-reported antisocial symptoms (β = 0.180, 95% confidence interval [CI]: 0.026-0.333), emotional distress (β = 0.224, 95% CI: 0.010-0.438), inattention (β = 0.349, 95% CI: 0.048-0.651), and lower global academic achievement (β = -0.127, 95% CI: -0.237-0.017) in second grade. Violent televiewing was also associated with less child-reported academic self-concept (β = -0.175, 95% CI: -0.296-0.053) and intrinsic motivation (β = -0.162, 95% CI: -0.016-0.307) in second grade. Effects remained significant after adjusting for preexisting child and family characteristics such as baseline child aggression. This prospective study suggests risks associated with early childhood violent media exposure for long-term mental health in children. These findings, suggesting diffusive relationships between early childhood violent media exposure and negative socioemotional and academic outcomes, empirically support the notion that access to early childhood violent television represents a threat to population health and should be discouraged by adult caregivers.

  11. Derivation of an occupational exposure level for manganese in welding fumes.

    PubMed

    Bailey, Lisa A; Kerper, Laura E; Goodman, Julie E

    2018-01-01

    Exposure to high levels of manganese (Mn) in occupational settings is known to lead to adverse neurological effects. Since Mn is an essential nutrient, there are mechanisms that maintain its homeostatic control in the body, and there is some level of Mn in air that does not perturb Mn homeostasis. However, the Mn exposure concentrations at which no adverse effects are expected in occupational settings vary considerably across regulatory agencies. We set out to derive a Mn Occupational Exposure Level (OEL) for welders based on a review of studies that evaluated Mn exposure concentrations from welding fumes and: (1) neurological effects in welders; (2) levels of Mn in the brains of welders (via pallidal index [PI] estimated from magnetic resonance imaging [MRI]); (3) other biomarkers of Mn exposure in welders (i.e., blood and urine); and (4) Mn brain concentrations, PI, and corresponding neurological effects in non-human primates. Our analysis suggests uncertainty in quantifying dose-response associations for Mn from many of the occupational welding studies. The few welding studies that adequately estimate exposure suggest a possible OEL of 100-140μg/m 3 for respirable Mn. This range is consistent with other epidemiology studies, studies of biomarkers of Mn exposure in welders, and with studies in non-human primates, though future studies could provide a stronger basis for deriving a Mn occupational guideline for welders. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The die is cast: arsenic exposure in early life and disease susceptibility.

    PubMed

    Thomas, David J

    2013-12-16

    Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for the development and progression of disease in both species. Mode of action and dosimetric studies in the mouse may help assess the role of age at exposure as a factor in susceptibility to the toxic and carcinogenic effects of arsenic in humans.

  13. Early-life chemical exposures and risk of metabolic syndrome.

    PubMed

    De Long, Nicole E; Holloway, Alison C

    2017-01-01

    The global prevalence of obesity has been increasing at a staggering pace, with few indications of any decline, and is now one of the major public health challenges worldwide. While obesity and metabolic syndrome (MetS) have historically thought to be largely driven by increased caloric intake and lack of exercise, this is insufficient to account for the observed changes in disease trends. There is now increasing evidence to suggest that exposure to synthetic chemicals in our environment may also play a key role in the etiology and pathophysiology of metabolic diseases. Importantly, exposures occurring in early life (in utero and early childhood) may have a more profound effect on life-long risk of obesity and MetS. This narrative review explores the evidence linking early-life exposure to a suite of chemicals that are common contaminants associated with food production (pesticides; imidacloprid, chlorpyrifos, and glyphosate) and processing (acrylamide), in addition to chemicals ubiquitously found in our household goods (brominated flame retardants) and drinking water (heavy metals) and changes in key pathways important for the development of MetS and obesity.

  14. Reducing radiation exposure during CRT implant procedures: early experience with a sensor-based navigation system.

    PubMed

    Thibault, Bernard; Andrade, Jason G; Dubuc, Marc; Talajic, Mario; Guerra, Peter G; Dyrda, Katia; Macle, Laurent; Rivard, Léna; Roy, Denis; Mondésert, Blandine; Khairy, Paul

    2015-01-01

    Cardiac resynchronization therapy (CRT) implant procedures are often complex and prolonged, resulting in significant ionizing radiation (IR) exposure to the patient and operator. We report our early experience working with a novel sensor-based electromagnetic tracking system (MediGuide™, MDG, St. Jude Medical Inc., St. Paul, MN, USA), in terms of procedural IR exposure reduction. Information regarding patient demographics, procedural details, procedural duration, and IR exposure were prospectively collected on 130 consecutive CRT procedures performed between January 2013 and January 2014. Sixty procedures were performed with MDG guidance, and 70 were performed without MDG guidance. Despite a nonsignificant trend toward shorter procedure duration with the use of MDG (120 minutes vs 138 minutes with non-MDG, P = 0.088), a 66% reduction in total IR exposure (median 769 μGray · m(2) vs 2,608 μGray · m(2), P < 0.001) was found. This reduction was primarily driven by a >90% reduction in IR dose required to cannulate the coronary sinus (median 80 μGray · m(2) vs 922 μGray · m(2), P < 0.001), and to a lesser extent from a reduction in IR dose required for LV lead placement (median 330 μGray·m(2) vs 737 μGray · m(2), P = 0.059). In addition, a significant learning curve effect was observed with a significantly shorter procedural duration for the last 15 cases compared to the first 15 cases (median 98 minutes vs 175 minutes, P < 0.001). The nonfluoroscopic MDG positioning system is associated with a dramatic reduction in exposure to IR during CRT implant procedures, with a 90% decrease in the IR dose required to cannulate the coronary sinus. A steep learning curve was quantified. ©2014 Wiley Periodicals, Inc.

  15. Phosphatidylserine metabolism modification precedes manganese-induced apoptosis and phosphatidylserine exposure in PC12 cells.

    PubMed

    Ferrara, G; Gambelunghe, A; Mozzi, R; Marchetti, M C; Migliorati, G; Muzi, G; Buratta, S

    2013-12-01

    Long-term exposure to high manganese (Mn) levels can lead to Parkinson-like neurological disorders. Molecular mechanisms underlying Mn cytotoxicity have been not defined. It is known that Mn induces apoptosis in PC12 cells and that this involves the activation of some signal transduction pathways. Although the role of phospholipids in apoptosis and signal transduction is well-known, the membrane phospholipid component in Mn-related damage has not yet been investigated. Phosphatidylserine (PS) facilitates protein translocation from cytosol to plasma membrane and PS exposure on the cell surface allows macrophage recognition of apoptotic cells. This study investigates the effects of MnCl2 on PS metabolism in PC12 cells, relating them to those on cell apoptosis. Apoptosis induction decreased PS radioactivity of PC12 cells incubated with radioactive serine. MnCl2 reduced PS radioactivity even under conditions that did not affect cell viability or PS exposure, suggesting that the effects on PS metabolism may represent an early event in cell apoptosis. Thus the latter conditions that also induced a greater PS decarboxylation were utilized for further investigating on the effects on PS synthesis, by measuring the activity and expression of PS-synthesizing enzymes, in cell lysates and in total cellular membranes (TM). Compared with corresponding controls, enzyme activity of MnCl2-treated cells was lower in cell lysates and greater in TM. Evaluating the expression of two isoforms of PS-synthesizing enzyme (PSS), PSSII was increased both in cell lysate and TM, while PSSI was unchanged. MnCl2 addition to control cell lysate reduced enzyme activity. These results suggest Mn plays a dual role on PS synthesis. Once inside the cell, Mn inhibits the enzyme/s, thus accounting for reduced PS synthesis in lysates and intact cells. On the other hand, it increases PSSII expression in cell membranes. The possibility that this occurs to counteract the direct effects of Mn ions on enzyme

  16. Epigenetics, obesity and early-life cadmium or lead exposure

    PubMed Central

    Park, Sarah S; Skaar, David A; Jirtle, Randy L; Hoyo, Cathrine

    2017-01-01

    Obesity is a complex and multifactorial disease, which likely comprises multiple subtypes. Emerging data have linked chemical exposures to obesity. As organismal response to environmental exposures includes altered gene expression, identifying the regulatory epigenetic changes involved would be key to understanding the path from exposure to phenotype and provide new tools for exposure detection and risk assessment. In this report, we summarize published data linking early-life exposure to the heavy metals, cadmium and lead, to obesity. We also discuss potential mechanisms, as well as the need for complete coverage in epigenetic screening to fully identify alterations. The keys to understanding how metal exposure contributes to obesity are improved assessment of exposure and comprehensive establishment of epigenetic profiles that may serve as markers for exposures. PMID:27981852

  17. Epigenetics, obesity and early-life cadmium or lead exposure.

    PubMed

    Park, Sarah S; Skaar, David A; Jirtle, Randy L; Hoyo, Cathrine

    2017-01-01

    Obesity is a complex and multifactorial disease, which likely comprises multiple subtypes. Emerging data have linked chemical exposures to obesity. As organismal response to environmental exposures includes altered gene expression, identifying the regulatory epigenetic changes involved would be key to understanding the path from exposure to phenotype and provide new tools for exposure detection and risk assessment. In this report, we summarize published data linking early-life exposure to the heavy metals, cadmium and lead, to obesity. We also discuss potential mechanisms, as well as the need for complete coverage in epigenetic screening to fully identify alterations. The keys to understanding how metal exposure contributes to obesity are improved assessment of exposure and comprehensive establishment of epigenetic profiles that may serve as markers for exposures.

  18. Associations among environmental exposure to manganese, neuropsychological performance, oxidative damage and kidney biomarkers in children.

    PubMed

    Nascimento, Sabrina; Baierle, Marília; Göethel, Gabriela; Barth, Anelise; Brucker, Natália; Charão, Mariele; Sauer, Elisa; Gauer, Bruna; Arbo, Marcelo Dutra; Altknecht, Louise; Jager, Márcia; Dias, Ana Cristina Garcia; de Salles, Jerusa Fumagalli; Saint' Pierre, Tatiana; Gioda, Adriana; Moresco, Rafael; Garcia, Solange Cristina

    2016-05-01

    Environmental exposure to manganese (Mn) results in several toxic effects, mainly neurotoxicity. This study investigated associations among Mn exposure, neuropsychological performance, biomarkers of oxidative damage and early kidney dysfunction in children aged 6-12 years old. Sixty-three children were enrolled in this study, being 43 from a rural area and 20 from an urban area. Manganese was quantified in blood (B-Mn), hair (H-Mn) and drinking water using inductively coupled plasma mass spectrometry (ICP-MS). The neuropsychological functions assessed were attention, perception, working memory, phonological awareness and executive functions - inhibition. The Intelligence quotient (IQ) was also evaluated. The biomarkers malondialdehyde (MDA), protein carbonyls (PCO), δ-aminolevulinate dehydratase (ALA-D), reactivation indexes with dithiothreitol (ALA-RE/DTT) and ZnCl2 (ALA-RE/ZnCl2), non-protein thiol groups, as well as microalbuminuria (mALB) level and N-acetyl-β-D-glucosaminidase (NAG) activity were assessed. The results demonstrated that Mn levels in blood, hair and drinking water were higher in rural children than in urban children (p<0.01). Adjusted for potential confounding factors, IQ, age, gender and parents' education, significant associations were observed mainly between B-Mn and visual attention (β=0.649; p<0.001). Moreover, B-Mn was negatively associated with visual perception and phonological awareness. H-Mn was inversely associated with working memory, and Mn levels from drinking water with written language and executive functions - inhibition. Rural children showed a significant increase in oxidative damage to proteins and lipids, as well as alteration in kidney function biomarkers (p<0.05). Moreover, significant associations were found between B-Mn, H-Mn and Mn levels in drinking water and biomarkers of oxidative damage and kidney function, besides between some oxidative stress biomarkers and neuropsychological tasks (p<0.05). The findings of this

  19. Environmental exposure to manganese and motor function of children in Mexico.

    PubMed

    Hernández-Bonilla, D; Schilmann, A; Montes, S; Rodríguez-Agudelo, Y; Rodríguez-Dozal, S; Solís-Vivanco, R; Ríos, C; Riojas-Rodríguez, H

    2011-10-01

    Occupational manganese (Mn) exposure has been associated with motor deficits in adult workers, but data on the potential effects of environmental exposure to Mn on the developing motor function for a children population is scarce. The aim of this study was to evaluate the association between exposure to Mn and motor function of school aged children. We conducted a cross-sectional study selecting 195 children (100 exposed and 95 unexposed) between 7 and 11 years old. The following tests were used to evaluate the motor function: Grooved pegboard, finger tapping, and Santa Ana test. Mn exposure was assessed by blood (MnB) and hair concentrations (MnH). We constructed linear regression models to evaluate the association between exposure to Mn and the different test scores adjusting for age, sex, maternal education, hemoglobin and blood lead. The median concentration of MnH and MnB was significantly higher in exposed (12.6 μg/g and 9.5 μg/L) compared to unexposed children (0.6 μg/g and 8.0 μg/L). The exposed children on average performed the grooved pegboard test faster, but made more errors, although these results did not reach statistical significance with neither one of the Mn exposure biomarkers. MnB showed an inverse association on the execution of the finger tapping test (average in 5 trials β -0.4, p=0.02), but no association was observed with MnH. A subtle negative association of Mn exposure on motor speed and coordination was shown. In adults, the main effect of environmental Mn exposure has been associated with motor skills, but these results suggest that such alterations are not the main effect on children. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Are There Effects of Intrauterine Cocaine Exposure on Delinquency during Early Adolescence? A Preliminary Report

    PubMed Central

    Gerteis, Jessie; Chartrand, Molinda; Martin, Brett; Cabral, Howard J.; Rose-Jacobs, Ruth; Crooks, Denise; Frank, Deborah A.

    2011-01-01

    Objective To ascertain whether level of intrauterine cocaine exposure (IUCE) is associated with early adolescent delinquent behavior, after accounting for prenatal exposures to other psychoactive substances and relevant psychosocial factors. Methods Ninety-three early adolescents (12.5–14.5 years old) participating since birth in a longitudinal study of IUCE reported delinquent acts via an audio computer assisted self interview (ACASI). Level of IUCE and exposure to cigarettes, alcohol, and marijuana were determined by maternal report, maternal and infant urine assays, and infant meconium assays at birth. Participants reported their exposure to violence on the Violence Exposure Scale for Children – Revised (VEX-R) at ages 8.5, 9.5, 11 years and during early adolescence, and the strictness of supervision by their caregivers during early adolescence. Results Of the 93 participants, 24 (26%) reported ≥3 delinquent behaviors during early adolescence. In the final multivariate model (including level of IUCE and cigarette exposure, childhood exposure to violence, and caregiver strictness/supervision) ≥ 3 delinquent behaviors were not significantly associated with level of IUCE but were significantly associated with intrauterine exposure to half a pack or more of cigarettes per day and higher levels of childhood exposure to violence, effects substantially unchanged after control for early adolescent violence exposure. Conclusions In this cohort, prospectively ascertained prenatal exposure to cigarettes and childhood exposure to violence are associated with self-reported delinquent behaviors during early adolescence. Contrary to initial popular predictions, intrauterine cocaine is not a strong predictor of adolescent delinquent behaviors in this cohort. PMID:21558951

  1. Ionic Strength-Controlled Mn (Hydr)oxide Nanoparticle Nucleation on Quartz: Effect of Aqueous Mn(OH)2.

    PubMed

    Jung, Haesung; Jun, Young-Shin

    2016-01-05

    The early formation of manganese (hydr)oxide nanoparticles at mineral-water interfaces is crucial in understanding how Mn oxides control the fate and transport of heavy metals and the cycling of nutrients. Using atomic force microscopy, we investigated the heterogeneous nucleation and growth of Mn (hydr)oxide under varied ionic strengths (IS; 1-100 mM NaNO3). Experimental conditions (i.e., 0.1 mM Mn(2+) (aq) concentration and pH 10.1) were chosen to be relevant to Mn remediation sites. We found that IS controls Mn(OH)2 (aq) formation, and that the controlled Mn(OH)2 (aq) formation can affect the system's saturation and subsequent Mn(OH)2 (s) and further Mn3O4 (s) nanoparticle formation. In 100 mM IS system, nucleated Mn (hydr)oxide particles had more coverage on the quartz substrate than those in 1 mM and 10 mM IS systems. This high IS also resulted in low supersaturation ratio and thus favor heterogeneous nucleation, having better structural matching between nucleating Mn (hydr)oxides and quartz. The unique information obtained in this work improves our understanding of Mn (hydr)oxide formation in natural as well as engineered aqueous environments, such as groundwater contaminated by natural leachate and acid mine drainage remediation.

  2. Exposure of Mn and FeSODs, but not Cu/ZnSOD, to NO leads to nitrosonium and nitroxyl ions generation which cause enzyme modification and inactivation: an in vitro study.

    PubMed

    Niketíc, V; Stojanović, S; Nikolić, A; Spasić, M; Michelson, A M

    1999-11-01

    The effect of NO treatment in vitro on structural and functional alterations of Cu/Zn, Mn, and Fe type of SODs was studied. Significant difference in response to NO of Cu/ZnSOD compared to the Mn and Fe types was demonstrated. Cu/ZnSOD was shown to be stable with respect to NO: even on prolonged exposure, NO produced negligible effect on its structure and activity. In contrast, both Mn and Fe types were found to be NO-sensitive: exposure to NO led to their fast and extensive inactivation, which was accompanied by extensive structural alterations, including (in some of the samples tested) the cleavage of enzyme polypeptide chains, presumably at His residues of the enzyme metal binding sites. The generation of nitrosonium (NO+) and nitroxyl (NO-) ions in NO treated Mn and FeSODs, which produce enzyme modifications and inactivation, was demonstrated. The physiological and biomedical significance of described findings is briefly discussed.

  3. Recovery from welding-fume-exposure-induced MRI T1 signal intensities after cessation of welding-fume exposure in brains of cynomolgus monkeys.

    PubMed

    Han, Jeong Hee; Chung, Yong Hyun; Park, Jung Duck; Kim, Choong Yong; Yang, Seoung Oh; Khang, Hyun Soo; Cheong, Hae Kwan; Lee, Jong Seong; Ha, Chang Soo; Song, Chang-Woo; Kwon, Il Hoon; Sung, Jae Hyuck; Heo, Jeong Doo; Kim, Na-Young; Huang, Mingai; Cho, Myung Haing; Yu, Il Je

    2008-09-01

    The shortening of the MRI T1 relaxation time, indicative of a high signal intensity in a T1-weighted MRI, is known as a useful biomarker for Mn exposure after short-term welding-fume exposure. A previous monkey experimental study found that the T1 relaxation times decreased time-dependently after exposure, and a visually detectable high signal intensity appeared after 150 days of exposure. The nadir for the shortening of the T1 relaxation time was also previously found to correspond well with the blood Mn concentration in welders, suggesting a correlation between a prolonged high blood Mn concentration and shortened T1 relaxation time. Accordingly, to clarify the clearance of the brain Mn concentration after the cessation of welding-fume exposure, cynomolgus monkeys were assigned to 3 groups-unexposed, low dose (31 mg/m(3) total suspended particulate (TSP), 0.9 mg Mn/m(3)), and high dose (62 mg/m(3) TSP, 1.95 mg Mn/m(3))-and exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day for 8 mo in an inhalation chamber system equipped with an automatic fume generator. After reaching the peak MRI T1 signal intensity (shortest T1 relaxation time), the monkeys were allowed to recover by ceasing the welding-fume exposure. Within 2 mo, the MRI T1 signal intensities for the exposed monkeys returned to nearly the same level as those for the unexposed monkeys, indicating the potential for recovery from a high MRI T1 signal intensity induced by welding-fume exposure, even after prolonged exposure. Clearance of the Mn tissue concentration was also demonstrated in the globus pallidus, plus other tissues from the brain, liver, spleen, and blood. In contrast, there was no clearance of the lung concentrations of Mn, indicating that a soluble form of Mn was transported to the blood and brain. Therefore, the solubility of Mn in welding fumes would appear to be an important determinant as regards the retention of blood Mn levels and brain tissue Mn

  4. Early-Life Soy Exposure and Gender-Role Play Behavior in Children

    PubMed Central

    Daniels, Julie L.; Edwards, Lloyd J.; Siega-Riz, Anna Maria; Rogan, Walter J.

    2011-01-01

    Background: Soy-based infant formula contains high levels of isoflavones. These estrogen-like compounds have been shown to induce changes in sexually dimorphic behaviors in animals exposed in early development. Objective: We examined gender-role play behavior in relation to soy-based and non-soy-based infant feeding methods among children in the Avon Longitudinal Study of Parents and Children. Methods: We studied 3,664 boys and 3,412 girls. Four exposure categories were created using data from questionnaires administered at 6 and 15 months postpartum: primarily breast, early formula (referent), early soy, and late soy. Gender-role play behavior was assessed using the Pre-School Activities Inventory (PSAI). Associations between infant feeding and PSAI scores at 42 months of age were assessed using linear regression. Post hoc analyses of PSAI scores at 30 and 57 months were also conducted. Results: Early-infancy soy use was reported for approximately 2% of participants. Mean [95% confidence interval (CI)] PSAI scores at 42 months were 62.3 (62.0, 62.6) and 36.9 (36.6, 37.2) for boys and girls, respectively. After adjustment, early soy (vs. early formula) feeding was associated with higher (less feminine) PSAI scores in girls (® = 2.66; 95% CI: 0.19, 5.12) but was not significantly associated with PSAI scores in boys. The association between soy exposure and PSAI scores in girls was substantially attenuated at 30 and 57 months. Conclusions: Although not consistent throughout childhood, early-life soy exposure was associated with less female-typical play behavior in girls at 42 months of age. Soy exposure was not significantly associated with play behavior in boys. PMID:21813368

  5. Early-life soy exposure and gender-role play behavior in children.

    PubMed

    Adgent, Margaret A; Daniels, Julie L; Edwards, Lloyd J; Siega-Riz, Anna Maria; Rogan, Walter J

    2011-12-01

    Soy-based infant formula contains high levels of isoflavones. These estrogen-like compounds have been shown to induce changes in sexually dimorphic behaviors in animals exposed in early development. We examined gender-role play behavior in relation to soy-based and non-soy-based infant feeding methods among children in the Avon Longitudinal Study of Parents and Children. We studied 3,664 boys and 3,412 girls. Four exposure categories were created using data from questionnaires administered at 6 and 15 months postpartum: primarily breast, early formula (referent), early soy, and late soy. Gender-role play behavior was assessed using the Pre-School Activities Inventory (PSAI). Associations between infant feeding and PSAI scores at 42 months of age were assessed using linear regression. Post hoc analyses of PSAI scores at 30 and 57 months were also conducted. Early-infancy soy use was reported for approximately 2% of participants. Mean [95% confidence interval (CI)] PSAI scores at 42 months were 62.3 (62.0, 62.6) and 36.9 (36.6, 37.2) for boys and girls, respectively. After adjustment, early soy (vs. early formula) feeding was associated with higher (less feminine) PSAI scores in girls (β = 2.66; 95% CI: 0.19, 5.12) but was not significantly associated with PSAI scores in boys. The association between soy exposure and PSAI scores in girls was substantially attenuated at 30 and 57 months. Although not consistent throughout childhood, early-life soy exposure was associated with less female-typical play behavior in girls at 42 months of age. Soy exposure was not significantly associated with play behavior in boys.

  6. Hair as a Biomarker of Environmental Manganese Exposure

    PubMed Central

    Eastman, Rachel R.; Jursa, Tom P.; Benedetti, Chiara; Lucchini, Roberto G.; Smith, Donald R.

    2013-01-01

    The absence of well-validated biomarkers of manganese (Mn) exposure in children remains a major obstacle for studies of Mn toxicity. We developed a hair cleaning methodology to establish the utility of hair as an exposure biomarker for Mn and other metals (Pb, Cr, Cu), using ICP-MS, scanning electron microscopy, and laser ablation ICP-MS to evaluate cleaning efficacy. Exogenous metal contamination on hair that was untreated or intentionally contaminated with dust or Mn-contaminated water was effectively removed using a cleaning method of 0.5% Triton X-100 sonication plus 1N nitric acid sonication. This cleaning method was then used on hair samples from children (n=121) in an ongoing study of environmental Mn exposure and related health effects. Mean hair Mn levels were 0.121 μg/g (median = 0.073 μg/g, range = 0.011 – 0.736 μg/g), which are ~4 to 70-fold lower than levels reported in other pediatric Mn studies. Hair Mn levels were also significantly higher in children living in the vicinity of active, but not historic, ferroalloy plant emissions compared to controls (P<0.001). These data show that exogenous metal contamination on hair can be effectively cleaned of exogenous metal contamination, and they substantiate the use of hair Mn levels as a biomarker of environmental Mn exposure in children. PMID:23259818

  7. Blood manganese as an exposure biomarker: State of the evidence

    PubMed Central

    Baker, Marissa G.; Simpson, Christopher D.; Stover, Bert; Sheppard, Lianne; Checkoway, Harvey; Racette, Brad A.; Seixas, Noah S.

    2014-01-01

    Despite evidence of adverse health effects resulting from exposure to manganese (Mn), biomarkers of exposure are poorly understood. To enhance understanding, mean blood Mn (MnB) and mean air Mn (MnA) were extracted from 63 exposure groups in 24 published papers, and the relationship was modeled using segmented regression. On a log/log scale, a positive association between MnA and MnB was observed among studies reporting MnA concentrations above about 10 μg/m3, although interpretation is limited by largely cross-sectional data, study design variability, and differences in exposure monitoring methods. Based on the results of the segmented regression, we hypothesize that below the concentration of about 10 μg/m3, Mn in the body is dominated by dietary Mn, and additional inhaled Mn only causes negligible changes in Mn levels unless the inhaled amount is substantial. However, stronger study designs are required to account for temporal characteristics of the MnA to MnB relationships which reflect the underlying physiology and toxicokinetics of Mn uptake and distribution. Thus, we present an inception cohort study design we have conducted among apprentice welders, and the analytical strengths this study design offers. To determine if blood could be a useful biomarker for Mn to be utilized by industrial hygienists in general industry requires additional time-specific analyses, which our inception cohort study design will allow. PMID:24579750

  8. Environmental Exposure to Manganese in Air: Associations ...

    EPA Pesticide Factsheets

    BACKGROUND: Manganese (Mn) inhalation has been associated with neuropsychological and neurological sequelae in exposed workers. Few environmental epidemiologic studies have examined the potentialy neurotoxic effects of Mn exposure in ambient air on motor function and hand tremor in adult community residents. Mn exposed residents were recruited in two Ohio towns: Marietta, a town near a ferro-manganese smelter, and East Liverpool, a town adjacent to a facility processing, crushing, screening, and packaging Mn products.METHODS: Chronic (≥10years) exposure to ambient air Mn in adult residents and effects on neuropsychological and neurological outcomes were investigated. Participants from Marietta (n=100) and East Liverpool (n=86) were combined for analyses. AERMOD dispersion modeling of fixed-site outdoor air monitoring data estimated Mn inhalation over a ten year period. Adult Mn­ exposed residents' psychomotor ability was assessed using Finger Tapping, Hand Dynamometer, Grooved Pegbcard, and the Computerized Adaptive Testing System (CATSYS) Tremor system.Bayesian structural equation modeling was used to assess associations between air-Mn and motor function and tremor .RESULTS: Air-Mn exposure was significantly correlated in bivariate analyses with the tremor test (CATSYS) for intensity, center frequency and harmonic index. The Bayesian path analysis model showed associations of air-Mn with the CATSYS non-dominant center frequency and harmonic ind

  9. Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

    PubMed

    Cooke, Gerard M

    2014-01-01

    The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

  10. Prenatal Mancozeb Exposure, Excess Manganese, and Neurodevelopment at 1 Year of Age in the Infants' Environmental Health (ISA) Study.

    PubMed

    Mora, Ana María; Córdoba, Leonel; Cano, Juan Camilo; Hernandez-Bonilla, David; Pardo, Larissa; Schnaas, Lourdes; Smith, Donald R; Menezes-Filho, José A; Mergler, Donna; Lindh, Christian H; Eskenazi, Brenda; van Wendel de Joode, Berna

    2018-05-01

    Although growing evidence suggests that early-life excess manganese (Mn) impairs neurodevelopment, data on the neurodevelopmental effects of mancozeb, a fungicide containing Mn, and its main metabolite ethylenethiourea (ETU) are limited. We examined whether prenatal mancozeb exposure and excess Mn were associated with neurodevelopment in 355 1-y-old infants living near banana plantations with frequent aerial mancozeb spraying in Costa Rica. We measured urinary ETU, hair Mn, and blood Mn concentrations in samples collected 1-3 times during pregnancy from mothers enrolled in the Infants' Environmental Health (ISA) study. We then assessed neurodevelopment in their 1-y-old infants using the Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III). We estimated exposure-outcome associations using linear regression models adjusted for maternal education, parity, gestational age at birth, child age, Home Observation for Measurement of the Environment score, and location of neurodevelopmental assessment. Median (P25-P75) urinary ETU, hair Mn, and blood Mn measured during pregnancy were 3.3 μg/L (2.4-4.9; specific gravity-corrected), 1.7 μg/g (0.9-4.1), and 24.0 μg/L (20.3-28.0), respectively. Among girls, higher ETU was associated with lower social-emotional scores [β per 10-fold increase=-7.4 points (95% CI: -15.2, 0.4)], whereas higher hair Mn was associated with lower cognitive scores [-3.0 (-6.1, 0.1)]. Among boys, higher hair Mn was associated with lower social-emotional scores [-4.6 (-8.5, -0.8)]. We observed null associations for blood Mn, language, and motor outcomes. Our findings indicate that maternal exposure to mancozeb and excess Mn during pregnancy may have adverse and sex-specific effects on infant neurodevelopment. https://doi.org/10.1289/EHP1955.

  11. Statistical modeling to determine sources of variability in exposures to welding fumes.

    PubMed

    Liu, Sa; Hammond, S Katharine; Rappaport, Stephen M

    2011-04-01

    Exposures to total particulate matter (TP) and manganese (Mn) received by workers during welding and allied hot processes were analyzed to assess the sources and magnitudes of variability. Compilation of data from several countries identified 2065 TP and 697 Mn measurements for analysis. Linear mixed models were used to determine fixed effects due to different countries, industries and trades, process characteristics, and the sampling regimen, and to estimate components of variance within workers (both intraday and interday), between workers (within worksites), and across worksites. The fixed effects explained 55 and 49% of variation in TP and Mn exposures, respectively. The country, industry/trade, type of ventilation, and type of work/welding process were the major factors affecting exposures to both agents. Measurements in the USA were generally higher than those in other countries. Exposure to TP was 67% higher in enclosed spaces and 43% lower with local exhaust ventilation (LEV), was higher among boilermakers and was higher when either a mild-steel base metal or a flux cored consumable was used. Exposure to Mn was 750% higher in enclosed spaces and 67% lower when LEV was present. Air concentrations of Mn were significantly affected by the welding consumables but not by the base metal. Resistance welding produced significantly lower TP and Mn exposures compared to other welding processes. Interestingly, exposures to TP had not changed over the 40 years of observation, while those of Mn showed (non-significant) reductions of 3.6% year(-1). After controlling for fixed effects, variance components between worksites and between-individual workers within a worksite were reduced by 89 and 57% for TP and 75 and 63% for Mn, respectively. The within-worker variation (sum of intraday and interday variance components) of Mn exposure was three times higher than that of TP exposure. The estimated probabilities of exceeding occupational exposure limits were very high

  12. Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes.

    PubMed

    Xu, Ning; Chua, Angela K; Jiang, Hong; Liu, Ning-Ai; Goodarzi, Mark O

    2014-08-01

    Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study.

  13. Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression

    PubMed Central

    Saravia, Jordy; You, Dahui; Thevenot, Paul; Lee, Greg I.; Shrestha, Bishwas; Lomnicki, Slawo; Cormier, Stephania A.

    2013-01-01

    Elevated levels of combustion-derived particulate matter (CDPM) are a risk factor for the development of lung diseases such as asthma. Studies have shown that CDPM exacerbates asthma, inducing acute lung dysfunction and inflammation; however, the impact of CDPM exposure on early immunological responses to allergens remains unclear. To determine the effects of early-life CDPM exposure on allergic asthma development in infants, we exposed infant mice to CDPM and then induced a mouse model of asthma using house dust mite (HDM) allergen. Mice exposed to CDPM+HDM failed to develop a typical asthma phenotype including airway hyperresponsiveness, Th2-inflammation, Muc5ac expression, eosinophilia, and HDM-specific Ig compared to HDM-exposed mice. Although HDM-specific IgE was attenuated, total IgE was two-fold higher in CDPM+HDM mice compared to HDM-mice. We further demonstrate that CDPM exposure during early life induced an immunosuppressive environment in the lung, concurrent with increases in tolerogenic dendritic cells and Tregs, resulting in suppression of Th2 responses. Despite having early immunosuppression, these mice develop severe allergic inflammation when challenged with allergen as adults. These findings demonstrate a mechanism whereby CDPM exposure modulates adaptive immunity, inducing specific-antigen tolerance while amplifying total IgE, and leading to a predisposition to develop asthma upon rechallenge later in life. PMID:24172848

  14. Early exposure of rotating magnetic fields promotes central nervous regeneration in planarian Girardia sinensis.

    PubMed

    Chen, Qiang; Lin, Gui-miao; Wu, Nan; Tang, Sheng-wei; Zheng, Zhi-jia; Lin, Marie Chia-mi; Xu, Gai-xia; Liu, Hao; Deng, Yue-yue; Zhang, Xiao-yun; Chen, Si-ping; Wang, Xiao-mei; Niu, Han-ben

    2016-05-01

    Magnetic field exposure is an accepted safe and effective modality for nerve injury. However, it is clinically used only as a supplement or salvage therapy at the later stage of treatment. Here, we used a planarian Girardia sinensis decapitated model to investigate beneficial effects of early rotary non-uniform magnetic fields (RMFs) exposure on central nervous regeneration. Our results clearly indicated that magnetic stimulation induced from early RMFs exposure significantly promoted neural regeneration of planarians. This stimulating effect is frequency and intensity dependent. Optimum effects were obtained when decapitated planarians were cultured at 20 °C, starved for 3 days before head-cutting, and treated with 6 Hz 0.02 T RMFs. At early regeneration stage, RMFs exposure eliminated edema around the wound and facilitated subsequent formation of blastema. It also accelerated cell proliferation and recovery of neuron functionality. Early RMFs exposure up-regulated expression of neural regeneration related proteins, EGR4 and Netrin 2, and mature nerve cell marker proteins, NSE and NPY. These results suggest that RMFs therapy produced early and significant benefit in central nervous regeneration, and should be clinically used at the early stage of neural regeneration, with appropriate optimal frequency and intensity. © 2016 Wiley Periodicals, Inc.

  15. Dog and cat exposure and respective pet allergy in early childhood.

    PubMed

    Pyrhönen, Kaisa; Näyhä, Simo; Läärä, Esa

    2015-05-01

    The association of dog and cat exposure in early childhood with the incidence of respective allergies has remained controversial. The aim of the study was to obtain population-based evidence on the association of early exposure to dog or cat, or both, with dog and cat allergies. The study population was identified from the nationwide population register comprising all children aged 1-4 yr (N = 4779) born between 2001 and 2005 and living in the province of South Karelia, Finland. Cross-sectional questionnaire data on pet exposure in infancy and physician-diagnosed pet allergies were obtained from 3024 participants and merged with longitudinally accumulated data on sIgE and skin prick tests indicating allergic sensitization abstracted from all patient records in the area. The adjusted relative incidence of positive test results (with 95% confidence intervals) was 2.69 (1.45-5.02) for dog and 5.03 (2.47-10.2) for cat allergens among children exposed to a respective pet alone compared with children without such exposure. The corresponding adjusted prevalence odds ratios for diagnosed dog and cat allergies were 1.75 (0.77-3.79) and 5.13 (2.30-11.4), respectively. The association between pet exposure and the incidence of positive test results was independent of parents' allergies. Early exposure to dog and cat at home is associated with a higher incidence of respective pet allergy during the first four years of life. Further evidence from population-based studies with longer follow-up is required to justify any recommendation concerning early pet contacts with a view to preventing pet allergies later in life. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Children's Prenatal Exposure to Drugs: Implications for Early Childhood Educators.

    ERIC Educational Resources Information Center

    Mayfield, Phyllis K.; Chapman, J. Keith

    1998-01-01

    Examines the effects of drug use during pregnancy on early and later child development, the extent of women's drug use, and behavioral and learning characteristics of children prenatally exposed to drugs. Provides intervention guidelines for early childhood settings including children with prenatal drug exposure, focusing on recommendations for…

  17. Induction of genomic instability after an acute whole-body exposure of mice to 56Fe ions

    NASA Astrophysics Data System (ADS)

    Rithidech, Kanokporn Noy; Supanpaiboon, Wisa; Honikel, Louise; Whorton, Elbert B.

    2009-10-01

    The purpose of this study was to evaluate dose-response relationships for the in vivo induction of micronuclei (MN) as a measure of both initial radiation damage and the induction of genomic instability. These measurements were made in mouse blood erythrocytes as a function of radiation dose, radiation quality, time after irradiation, and the genetic background of exposed individuals. Blood samples were collected from two strains of mouse (CBA/CaJ and C57BL/6J) at different times up to 3 months following a whole-body exposure to various doses of 1 GeV/amu 56Fe ions (0, 0.1, 0.5 and 1.0 Gy, at the dose rate of a 1 Gy/min) or 137Cs gamma rays (0, 0.5, 1.0 and 3.0 Gy, at the dose rate of 0.72 Gy/min). Blood-smear slides were stained with acridine orange (AO). The frequencies of MN were measured in mature normochromatic-erythrocytes (MN-NCEs) and in immature polychromatic-erythrocytes (MN-PCEs). Effects of both types of radiation on erythropoiesis were also evaluated. As a measure of cell progression delay, a dose-dependent decrease in numbers of PCEs was observed at day 2 post-exposure in both strains, regardless of radiation quality. Subsequently, the levels of PCEs increased in all exposed mice, reaching control levels (or higher) by day 7 post-exposure. Further, at day 2 after the exposure, there was no increase in the frequency of MN-PCEs in CBA/CaJ mice exposed to 56Fe ions while the frequency of MN-PCEs elevated as a function of dose in the C57BL/6J mice. At day 4, there was no dose related increase in MN-NCEs in either strain of mouse exposed to 137Cs gamma rays. Additionally, at the early sacrifice times (days 2 and 4), 56Fe ions were slightly more effective (per unit dose) in inducing MN-NCEs than 137Cs gamma rays in CBA/CaJ mice. However, there was no increase in the frequency of MN-NCEs at late times after an acute exposure to either type of radiation. In contrast, both types of radiation induced increased MN-PCEs frequencies in irradiated CBA/CaJ mice, but

  18. Long-Term Neurotoxic Effects of Early Life Exposure to Tetrachloroethylene-contaminated Drinking Water

    PubMed Central

    Aschengrau, Ann; Janulewicz, Patricia A.; White, Roberta F.; Vieira, Veronica M.; Gallagher, Lisa G.; Getz, Kelly D.; Webster, Thomas F.; Ozonoff, David M.

    2016-01-01

    Background Tetrachloroethene (PCE) is a common environmental and occupational contaminant and an acknowledged neurotoxicant. From 1968 through 1983 widespread contamination of public drinking water supplies with PCE occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distribution pipes. Objectives A retrospective cohort study (“the Cape Cod Health Study”) was undertaken to examine possible health consequences of early life exposure to PCE-contaminated drinking water. This review describes the study methods and findings regarding the impact of prenatal and childhood exposure on neurological outcomes during early adulthood, including vision, neuropsychological functioning, brain structure, risky behaviors, and mental illness. The review also describes the strengths and challenges of conducting population-based epidemiological research in this unique setting. Methods Subjects were identified by cross-matching birth certificate and water system data. Information on health outcomes and confounding variables was collected from self-administered surveys (N= 1,689), neuropsychological tests (N=63), vision exam (N=63), and magnetic resonance imaging (N=42). Early life exposure to PCE was estimated using a leaching and transport model. The data analysis compared the occurrence of each health outcome among subjects with prenatal and early childhood PCE exposure to unexposed subjects while considering the impact of confounding variables. Results The study found evidence that early life exposure to PCE-contaminated drinking water has long-term neurotoxic effects. The strongest associations were seen with illicit drug use, bipolar disorder, and post-traumatic stress disorder. Key strengths of the study were availability of historical data on affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little confounding. Challenges arose mainly from

  19. Predicting Later-Life Outcomes of Early-Life Exposures

    EPA Science Inventory

    Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.Objectives: We examined the current state of understanding of later-life diseases resulting from ea...

  20. Early alcohol exposure impairs ocular dominance plasticity throughout the critical period.

    PubMed

    Medina, Alexandre E; Ramoa, Ary S

    2005-06-09

    Animal models of fetal alcohol syndrome (FAS) have revealed an impairment of sensory neocortex plasticity. Here, we examine whether early alcohol exposure leads to a permanent impairment of ocular dominance plasticity (OD) or to an alteration in the timing of the critical period. Ferrets were exposed to alcohol during a brief period of development prior to eye opening and effects of monocular deprivation examined during early, mid and late critical period. Single-unit electrophysiology revealed markedly reduced OD plasticity at every age examined. This finding provides evidence that early alcohol exposure does not affect the timing or duration of the critical period of OD plasticity and suggests an enduring impairment of neural plasticity in FAS.

  1. Early adolescent exposure to alcohol advertising and its relationship to underage drinking.

    PubMed

    Collins, Rebecca L; Ellickson, Phyllis L; McCaffrey, Daniel; Hambarsoomians, Katrin

    2007-06-01

    To determine whether early adolescents who are exposed to alcohol marketing are subsequently more likely to drink. Recent studies suggest that exposure to alcohol ads has a limited influence on drinking in mid-adolescence. Early adolescents may be more vulnerable to alcohol advertising effects. Two in-school surveys of 1786 South Dakota youth measured exposure to television beer advertisements, alcohol ads in magazines, in-store beer displays and beer concessions, radio-listening time, and ownership of beer promotional items during 6th grade, and drinking intentions and behavior at 7th grade. Multivariate regression equations predicted the two drinking outcomes using the advertising exposure variables and controlling for psychosocial factors and prior drinking. After adjusting for covariates, the joint effect of exposure to advertising from all six sources at grade 6 was strongly predictive of grade 7 drinking and grade 7 intentions to drink. Youth in the 75th percentile of alcohol marketing exposure had a predicted probability of drinking that was 50% greater than that of youth in the 25th percentile. Although causal effects are uncertain, policy makers should consider limiting a variety of marketing practices that could contribute to drinking in early adolescence.

  2. Early Embryonic Androgen Exposure Induces Transgenerational Epigenetic and Metabolic Changes

    PubMed Central

    Xu, Ning; Chua, Angela K.; Jiang, Hong; Liu, Ning-Ai

    2014-01-01

    Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study. PMID:24992182

  3. Protective effect of Mn(III)-desferrioxamine B upon oxidative stress caused by ozone and acid rain in the Brazilian soybean cultivar Glycine max "Sambaiba".

    PubMed

    Esposito, Jéssica Bordotti Nobre; Esposito, Breno Pannia; Azevedo, Ricardo Antunes; Cruz, Luciano Soares; da Silva, Luzimar Campos; de Souza, Silvia Ribeiro

    2015-04-01

    This study aimed to investigate the effects of the Mn complex (Mn(III)-desferrioxamine B (MnDFB)) on oxidative stress in the Brazilian soybean cultivar Glycine max "Sambaiba" following exposure to ozone and acid rain. We determined the suitable dose of MnDFB to apply to G. max seedlings using a dose-response curve. The highest superoxide dismutase (SOD) activity and Mn content in leaves were found upon the application of 8 μM MnDFB. Thus, G. max seedlings pretreated with 8 μM MnDFB were individually exposed to ozone and acid rain simulated. Pretreatment with MnDFB reduced lipid peroxidation upon ozone exposure and increased SOD activity in leaves; it did not alter the metal content in any part of the plant. Conversely, following acid rain exposure, neither the metal content in leaves nor SOD enzyme activity were directly affected by MnDFB, unlike pH. Our findings demonstrated that exogenous MnDFB application before ozone exposure may modulate the MnSOD, Cu/ZnSOD, and FeSOD activities to combat the ROS excess in the cell. Here, we demonstrated that the applied dose of MnDFB enhances antioxidative defenses in soybean following exposure to acid rain and especially to ozone.

  4. Early life exposure to ambient air pollution and childhood asthma in China.

    PubMed

    Deng, Qihong; Lu, Chan; Norbäck, Dan; Bornehag, Carl-Gustaf; Zhang, Yinping; Liu, Weiwei; Yuan, Hong; Sundell, Jan

    2015-11-01

    Early life is suggested to be a critical time in determining subsequent asthma development, but the extent to which the effect of early-life exposure to ambient air pollution on childhood asthma is unclear. We investigated doctor-diagnosed asthma in preschool children due to exposure to ambient air pollution in utero and during the first year of life. In total 2490 children aged 3-6 years participated in a questionnaire study regarding doctor-diagnosed asthma between September 2011 and January 2012 in China. Children's exposure to critical air pollutants, sulfur dioxide (SO2) as proxy of industrial air pollution, nitrogen dioxide (NO2) as proxy of traffic pollution, and particulate matter≤10µm in diameter (PM10) as a mixture, was estimated from the concentrations measured at the ambient air quality monitoring stations by using an inverse distance weighted (IDW) method. Logistic regression analysis was employed to determine the relationship between early-life exposure and childhood asthma in terms of odds ratio (OR) and 95% confidence interval (CI). Association between early-life exposure to air pollutants and childhood asthma was observed. SO2 and NO2 had significant associations with adjusted OR (95% CI) of 1.45 (1.02-2.07) and 1.74 (1.15-2.62) in utero and 1.62 (1.01-2.60) and 1.90 (1.20-3.00) during the first year for per 50 µg/m(3) and 15 µg/m(3) increase respectively. Exposure to the combined high level of SO2 and NO2 in China significantly elevated the asthmatic risk with adjusted OR (95% CI) of 1.76 (1.18-2.64) in utero and 1.85 (1.22-2.79) during the first year compared to the low level exposure. The associations were higher for males and the younger children aged 3-4 than females and the older children aged 5-6. Early-life exposure to ambient air pollution is associated with childhood asthma during which the level and source of air pollution play important roles. The high level and nature of combined industrial and traffic air pollution in China may

  5. A Possible Neuroprotective Action of a Vinylic Telluride against Mn-Induced Neurotoxicity

    PubMed Central

    Ávila, Daiana S.; Colle, Dirleise; Gubert, Priscila; Palma, Aline S.; Puntel, Gustavo; Manarin, Flávia; Noremberg, Simone; Nascimento, Paulo C.; Aschner, Michael; Rocha, João B. T.; Soares, Félix A. A.

    2010-01-01

    Manganese (Mn) is a metal required by biological systems. However, environmental or occupational exposure to high levels of Mn can produce a neurological disorder called manganism, which has similarities to Parkinson's disease. Diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP) is an organotellurium compound with a high antioxidant activity, especially in the brain. The present study was designed to investigate the effects of long-term low-dose exposure to Mn in drinking water on behavioral and biochemical parameters in rats and to determine the effectiveness of vinylic telluride in attenuating the effects of Mn. After 4 months of treatment with MnCl2 (13.7 mg/kg), rats exhibited clear signs of neurobehavioral toxicity, including a decrease in the number of rearings in the open field and altered motor performance in rotarod. The administration of DPTVP (0.150 μmol/kg, ip, 2 weeks) improved the motor performance of Mn-treated rats, indicating that the compound could be reverting Mn neurotoxicity. Ex vivo, we observed that Mn concentrations in the Mn-treated group were highest in the striatum, consistent with a statistically significant decrease in mitochondrial viability and [3H]glutamate uptake, and increased lipid peroxidation. Mn levels in the hippocampus and cortex were indistinguishable from controls, and no significant differences were noted in the ex vivo assays in these areas. Treatment with DPTVP fully reversed the biochemical parameters altered by Mn. Furthermore, DPTVP treatment was also associated with a reduction in striatal Mn levels. Our results demonstrate that DPTVP has neuroprotective activity against Mn-induced neurotoxicity, which may be attributed to its antioxidant activity and/or its effect on striatal Mn transport. PMID:20133376

  6. Latent carcinogenicity of early-life exposure to dichloroacetic acid in mice

    EPA Science Inventory

    AbstractEnvironmental exposures occurring early in life may have an important influence on cancer risk later in life. Here we investigated carryover effects of young-adult exposure to dichloroacetic acid (DCA), a small molecule analog of pyruvate and low-level environmental cont...

  7. Bioavailability and Toxicity of Copper, Manganese, and Nickel in Paronychiurus kimi (Collembola), and Biomarker Discovery for Their Exposure.

    PubMed

    Son, Jino; Lee, Yun-Sik; Lee, Sung-Eun; Shin, Key-Il; Cho, Kijong

    2017-01-01

    Bioavailability and toxicity of Cu, Mn, and Ni in Paronychiurus kimi were investigated after 28 days of exposure to OECD artificial soil spiked with these metals. Uptake and effect of Cu, Mn, and Ni on the reproduction of P. kimi were related to different metal fractions (water-soluble, 0.01 M CaCl 2 -extractable or porewater metal concentrations). Cu and Mn concentrations in P. kimi increased with increasing Cu and Mn concentrations in the soil, while Ni contents in P. kimi reached a plateau at a concentration higher than 200 mg/kg in soil. Both uptake and juvenile production related well to different metal fractions, suggesting that these metal fractions are suitable for assessing bioavailability and toxicity of metals in P. kimi. When toxicity for reproduction was compared, as reflected by EC 50 values, the order of metal toxicity varied depending upon how exposure concentration was expressed. Moreover, the results of proteomic analysis showed that several proteins involved in the immune system, neuronal outgrowth, and metal ion binding were up-regulated in P. kimi following short-term (7 days) exposure to sublethal level (corresponding to 50% of the EC 50 ) of Cu, Mn, or Ni, respectively. This suggests that the ecotoxicoproteomic approach seems to be a promising tool for early exposure warnings below which significant adverse effects are unlikely to occur. This study demonstrated that a combination of chemical and biological measures can provide information about metal bioavailability and toxicity to which P. kimi has been exposed.

  8. Impact of Early Postnatal Androgen Exposure on Voice Development

    PubMed Central

    Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.

    2012-01-01

    Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

  9. Arsenic and manganese exposure and children's intellectual function.

    PubMed

    Wasserman, Gail A; Liu, Xinhua; Parvez, Faruque; Factor-Litvak, Pam; Ahsan, Habibul; Levy, Diane; Kline, Jennie; van Geen, Alexander; Mey, Jacob; Slavkovich, Vesna; Siddique, Abu B; Islam, Tariqul; Graziano, Joseph H

    2011-08-01

    Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase focus on co-exposure to multiple toxicants. Earlier reports, including our own work in Bangladesh, have demonstrated independent associations between neurobehavioral function and exposure to both arsenic (As) and manganese (Mn) in school-aged children. Our earlier studies, however, were not designed to examine possible interactive effects of exposure to both As and Mn. To allow investigation of possible synergistic impact of simultaneous exposures, we recruited a new sample of 299 8-11 year old children, stratified by design on As (above and below 10 μg/L) and Mn (above and below 500 μg/L) concentrations of household wells. When adjusted only for each other, both As and Mn in whole blood (BAs; BMn) were significantly negatively related to most WISC-IV subscale scores. With further adjustment for socio-demographic features and ferritin, BMn remained significantly associated with reduced Perceptual Reasoning and Working Memory scores; associations for BAs, and for other subscales, were expectably negative, significantly for Verbal Comprehension. Urinary As (per gram creatinine) was significantly negatively associated with Verbal Comprehension scores, even with adjustment for BMn and other contributors. Mn by As interactions were not significant in adjusted or unadjusted models (all p's>0.25). Findings are consistent with other reports documenting adverse impact of both As and Mn exposure on child developmental outcomes, although associations appear muted at these relatively low exposure levels. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. ADVERSE HEALTH EFFECTS FROM ENVIRONMENTAL MANGANESE EXPOSURE.

    EPA Science Inventory

    The ubiquitous element, manganese (Mn), is an essential nutrient, but toxic at excessive exposure levels. Therefore, the US EPA set guideline levels for Mn exposure through inhalation (reference concentration-RfC=0.05 ?g/m3) and ingestion (reference dose-RfD=0.14 mg/kg/day (10 mg...

  11. Early Adolescent Exposure to Alcohol Advertising and Its Relationship to Underage Drinking

    PubMed Central

    Collins, Rebecca L.; Ellickson, Phyllis L.; McCaffrey, Daniel; Hambarsoomians, Katrin

    2009-01-01

    Purpose To determine whether early adolescents who are exposed to alcohol marketing are subsequently more likely to drink. Recent studies suggest that exposure to alcohol ads has a limited influence on drinking in mid-adolescence. Early adolescents may be more vulnerable to alcohol advertising effects. Methods Two in-school surveys of 1,786 South Dakota youth measured exposure to television beer advertisements, alcohol ads in magazines, in-store beer displays and beer concessions, radio-listening time, and ownership of beer promotional items during sixth grade, and drinking intentions and behavior at seventh grade. Multivariate regression equations predicted the two drinking outcomes using the advertising exposure variables and controlling for psychosocial factors and prior drinking. Results After adjusting for covariates, the joint effect of exposure to advertising from all six sources at Grade 6 was strongly predictive of Grade 7 drinking and Grade 7 intentions to drink. Youth in the 75th percentile of alcohol marketing exposure had a predicted probability of drinking that was 50% greater than that of youth in the 25th percentile. Conclusions Although causal effects are uncertain, policy makers should consider limiting a variety of marketing practices that could contribute to drinking in early adolescence. PMID:17531759

  12. Energetics of cubic and hexagonal phases in Mn-doped GaN : First-principles pseudopotential calculations

    NASA Astrophysics Data System (ADS)

    Choi, Eun-Ae; Kang, Joongoo; Chang, K. J.

    2006-12-01

    We perform first-principles pseudopotential calculations to study the influence of Mn doping on the stability of two polytypes, wurtzite and zinc-blende, in GaN . In Mn δ -doped GaN and GaMnN alloys, we find similar critical concentrations of the Mn ions for stabilizing the zinc-blende phase against the wurtzite phase. Using a slab geometry of hexagonal lattices, we find that it is energetically unfavorable to form inversion domains with Mn exposure, in contrast to Mg doping. At the initial stage of epitaxial growth, a stacking fault that leads to the cubic bonds can be generated with the Mn exposure to the Ga-polar surface. However, the influence of the Mn δ -doped layer on the formation of the cubic phase is only effective for GaN layers deposited up to two monolayers. We find that the Mn ions are energetically more stable on the growth front than in the bulk, indicating that these ions act as a surfactant. Thus it is possible to grow cubic GaN if the Mn ions are periodically supplied or diffuse out from the Mn δ -doped layer to the growth front during the growth process.

  13. Manganese in the shell of the bivalve Mytilus edulis: Seawater Mn or physiological control?

    NASA Astrophysics Data System (ADS)

    Freitas, Pedro S.; Clarke, Leon J.; Kennedy, Hilary; Richardson, Christopher A.

    2016-12-01

    Manganese in the shell calcite of marine bivalves has been suggested to reflect ambient seawater Mn concentrations, thus providing a high-resolution archive of past seawater Mn concentrations. However, a quantitative relationship between seawater Mn and shell Mn/Ca ratios, as well as clear understanding of which process(es) control(s) shell Mn/Ca, are still lacking. Blue mussels, Mytilus edulis, were grown in a one-year duration field experiment in the Menai Strait, U.K., to study the relationship between seawater particulate and dissolved Mn2+ concentrations and shell calcite Mn/Ca ratios. Shell Mn/Ca showed a well-defined intra-annual double-peak, with maximum values during early spring and early summer and low values during autumn and winter. Seawater particulate Mn peaked during winter and autumn, with a series of smaller peaks during spring and summer, whereas dissolved Mn2+ exhibited a marked single maximum during late-spring to early-summer, being low during the remainder of the year. Consequently, neither seawater particulate Mn nor dissolved Mn2+ concentrations explain the intra-annual variation of shell Mn/Ca ratios. A physiological control on shell Mn/Ca ratios is evident from the strong similarity and timing of the double-peaked intra-annual variations of Mn/Ca and shell growth rate (SGR), the latter corresponding to periods of increased metabolic activity (as indicated by respiration rate). It is thus likely that in M. edulis SGR influences shell Mn/Ca by altering the concentration or activity of Mn2+ within the extra-pallial fluid (EPF), by changing the flux of Mn into or the proportion of protein bound Mn within the EPF. By linking shell Mn/Ca ratios to the endogenous and environmental factors that determine growth and metabolic activity, this study helps to explain the lack of a consistent relationship between shell Mn/Ca in marine bivalve shell calcite and seawater particulate and dissolved Mn2+ concentrations. The use of Mn content from M. edulis

  14. The Exposure Advantage: Early Exposure to a Multilingual Environment Promotes Effective Communication.

    PubMed

    Fan, Samantha P; Liberman, Zoe; Keysar, Boaz; Kinzler, Katherine D

    2015-07-01

    Early language exposure is essential to developing a formal language system, but may not be sufficient for communicating effectively. To understand a speaker's intention, one must take the speaker's perspective. Multilingual exposure may promote effective communication by enhancing perspective taking. We tested children on a task that required perspective taking to interpret a speaker's intended meaning. Monolingual children failed to interpret the speaker's meaning dramatically more often than both bilingual children and children who were exposed to a multilingual environment but were not bilingual themselves. Children who were merely exposed to a second language performed as well as bilingual children, despite having lower executive-function scores. Thus, the communicative advantages demonstrated by the bilinguals may be social in origin, and not due to enhanced executive control. For millennia, multilingual exposure has been the norm. Our study shows that such an environment may facilitate the development of perspective-taking tools that are critical for effective communication. © The Author(s) 2015.

  15. Manganese accumulation in hair and teeth as a biomarker of manganese exposure and neurotoxicity in rats.

    PubMed

    Liang, Guiqiang; Zhang, Li'e; Ma, Shuyan; Lv, Yingnan; Qin, Huiyan; Huang, Xiaowei; Qing, Li; Li, Qin; Chen, Kangcheng; Xiong, Feng; Ma, Yifei; Nong, Jie; Yang, Xiaobo; Zou, Yunfeng

    2016-06-01

    Manganese (Mn) is an essential trace element to humans. However, excessive Mn causes cognitive impairment resulting from injury to the central nervous system within the hippocampus. No ideal biomarker is currently available for evaluating Mn exposure and associated neurotoxicity in the body. Hence, this study used Mn levels in the serum (MnS), teeth (MnT), and hair (MnH) as biomarkers for evaluating the association between Mn exposure and cognitive impairment in Mn-treated rats. A total of 32 male Sprague-Dawley rats were randomly divided into four groups, received 0, 5, 10, and 20 mg/(kg day) of MnCl2·4H2O for 5 days a week for 18 weeks, respectively. Lifetime Mn cumulative dose (LMCD) was used to evaluate external Mn exposure. Hippocampus, serum, teeth, and hair specimens were collected from the rats for Mn determination by graphite furnace atomic absorption spectrometry. Learning and memory functions were assessed using the Morris water maze test. Results showed that chronic Mn exposure increased the hippocampus (MnHip), MnS, MnT, and MnH levels, as well as impaired learning and memory function in rats. MnHip, MnT, and MnH levels were positively correlated with LMCD (r = 0.759, r = 0.925, and r = 0.908, respectively; p < 0.05), escape latency (r = 0.862, r = 0.716, and r = 0.814, respectively; p < 0.05), and the number of platform crossings (r = -0.734, r = -0.514, and r = -0.566, respectively; p < 0.05). No association was observed between MnS levels and the number of platform crossings (r = -0.286, p > 0.05). Thus, MnT and MnH detected long-term low-dose Mn exposure. These parameters can be reliable biomarkers for Mn exposure and associated neurotoxicity in Mn-treated rats.

  16. Long-term Neurotoxic Effects of Early-life Exposure to Tetrachloroethylene-contaminated Drinking Water.

    PubMed

    Aschengrau, Ann; Janulewicz, Patricia A; White, Roberta F; Vieira, Veronica M; Gallagher, Lisa G; Getz, Kelly D; Webster, Thomas F; Ozonoff, David M

    2016-01-01

    Tetrachloroethene (PCE) is a common environmental and occupational contaminant and an acknowledged neurotoxicant. From 1968 through 1983, widespread contamination of public drinking water supplies with PCE occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distribution pipes. A retrospective cohort study (the Cape Cod Health Study) was undertaken to examine possible health consequences of early-life exposure to PCE-contaminated drinking water. This review describes the study methods and findings regarding the effects of prenatal and childhood exposure on neurologic outcomes during early adulthood, including vision, neuropsychological functioning, brain structure, risky behaviors, and mental illness. The review also describes the strengths and challenges of conducting population-based epidemiologic research in this unique setting. Participants were identified by cross-matching birth certificates and water system data. Information on health outcomes and confounding variables was collected from self-administered surveys (n = 1689), neuropsychological tests (n = 63), vision examinations (n = 63), and magnetic resonance imaging (n = 42). Early-life exposure to PCE was estimated using a leaching and transport model. The data analysis compared the occurrence of each health outcome among individuals with prenatal and early childhood PCE exposure to unexposed individuals while considering the effect of confounding variables. The study found evidence that early-life exposure to PCE-contaminated drinking water has long-term neurotoxic effects. The strongest associations were seen with illicit drug use, bipolar disorder, and post-traumatic stress disorder. Key strengths of the study were availability of historical data on affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little confounding. Challenges arose mainly from the historical

  17. Adult Neuropsychological Performance Following Prenatal and Early Postnatal Exposure to Tetrachloroethylene (PCE)-contaminated Drinking Water

    PubMed Central

    Janulewicz, Patricia A; White, Roberta F; Martin, Brett M; Winter, Michael R; Weinberg, Janice M; Vieira, Veronica; Aschengrau, Ann

    2012-01-01

    This population-based retrospective cohort study examined adult performance on a battery of neuropsychological tests in relation to prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using pipe network information from town water departments, a PCE leaching and transport algorithm, EPANet water flow modeling software, and a Geographic Information System (GIS). Results of crude and multivariate analyses among 35 exposed and 28 unexposed subjects showed no association between prenatal and early postnatal exposure and decrements on tests that assess abilities in the domains of omnibus intelligence, academic achievement or language. The results were suggestive of an association between prenatal and early postnatal PCE exposure and diminished performance on tests that assessed abilities in the domains of visuospatial functioning, learning and memory, motor, attention and mood. Because the sample size was small, most findings were not statistically significant. Future studies with larger sample sizes should be conducted to further define the neuropsychological consequences of early developmental PCE exposure. PMID:22522125

  18. Early Exposure to Toxic Substances Damages Brain Architecture. Working Paper #4

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2006

    2006-01-01

    New science shows that exposure to toxins prenatally or early in life can have a devastating and lifelong effect on the developing architecture of the brain. Exposures to many chemicals have much more severe consequences for embryos, fetuses, and young children, whose brains are still developing, than for adults. Substances that can have a truly…

  19. Associations between former exposure to manganese and olfaction in an elderly population: Results from the Heinz Nixdorf Recall Study.

    PubMed

    Casjens, Swaantje; Pesch, Beate; Robens, Sibylle; Kendzia, Benjamin; Behrens, Thomas; Weiss, Tobias; Ulrich, Nadin; Arendt, Marina; Eisele, Lewin; Pundt, Noreen; Marr, Anja; van Thriel, Christoph; Van Gelder, Rainer; Aschner, Michael; Moebus, Susanne; Dragano, Nico; Jöckel, Karl-Heinz; Brüning, Thomas

    2017-01-01

    Occupational exposure to manganese (Mn) has been associated with impairments in olfaction and motor functions, but it has yet to be determined if such effects persist upon cessation of exposure. The objective of this study was to evaluate the influence of former occupational Mn exposure on olfaction within the framework of a prospective cohort study among an elderly German population. Information on job tasks with recognized Mn exposure and data on odor identification assessed with Sniffin' sticks was collected during the second follow-up of the Heinz Nixdorf Recall Study. The study population consisted of 1385 men aged 55-86 years, 354 of whom ever worked in jobs with potential Mn exposure (median 58.3μg/m 3  years, interquartile range 19.0-185μg/m 3  years). Multiple exposure measures, including job tasks, cumulative Mn exposure, and Mn determined in blood samples (MnB) archived at baseline, were used to estimate effects of Mn on olfaction. Having ever worked as welder was associated with better olfaction compared to other blue-collar workers without Mn exposure. Blue-collar workers identified less odors in comparison to white-collar workers. Concentrations of previous Mn exposure >185μg/m 3  years or MnB ≥15μg/L were not associated with impaired olfaction. In addition to a strong age effect, participants with lower occupational qualification identified less odors. We found no relevant association of former Mn exposure at relatively low levels with impaired olfaction. Possible neurotoxic Mn effects may not be persistent after cessation. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Water dissociation on Mn(1×1)/Ag(100)

    DOE PAGES

    Arble, Chris; Tong, Xiao; Giordano, Livia; ...

    2016-08-19

    In this work we utilize experimental and simulation techniques to examine the molecular level interaction of water with a MnO(1×1) thin film deposited onto Ag(100). The formation of MnO(1×1)/Ag(100) was characterized by low energy electron diffraction and scanning tunneling microscopy. Density functional theory (DFT) shows MnO(1×1) is thermodynamically more stable than MnO(2×1) by –0.4 eV per MnO. Upon exposure to 2.5 Torr water vapor at room temperature, X-ray photoemission spectroscopy results show extensive surface hydroxylation attributed to reactivity at MnO(1×1) terrace sites. DFT calculations of a water monomer on MnO(1×1)/Ag(100) show the dissociated form is energetically more favorable than molecularmore » adsorption, with a hydroxylation activation barrier 0.4 eV per H 2O. Lastly, these results are discussed and contrasted with previous studies of MgO/Ag(100) which show a stark difference in behavior for water dissociation.« less

  1. Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure.

    PubMed

    Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Yuan, Yan; Liaw, Jane; Durán, Viviana; Cuevas, Susana; García, José; Meza, Rodrigo; Valdés, Rodrigo; Valdés, Gustavo; Benítez, Hugo; VanderLinde, Vania; Villagra, Vania; Cantor, Kenneth P; Moore, Lee E; Perez, Saida G; Steinmaus, Scott; Smith, Allan H

    2014-08-01

    From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer. We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls. ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ≤110, 110 to 800, and >800 μg/L were 1.00, 1.88 [95% confidence interval (CI), 0.96-3.71], and 5.24 (3.05-9.00; P(trend) < 0.001) for lung cancer, and 1.00, 2.94 (1.29-6.70), and 8.11 (4.31-15.25; P(trend) < 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 μg/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed. Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure. Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. ©2014 American Association for Cancer Research.

  2. The developmental neurotoxicity of arsenic: cognitive and behavioral consequences of early life exposure.

    PubMed

    Tolins, Molly; Ruchirawat, Mathuros; Landrigan, Philip

    2014-01-01

    More than 200 million people worldwide are chronically exposed to arsenic. Arsenic is a known human carcinogen, and its carcinogenic and systemic toxicity have been extensively studied. By contrast, the developmental neurotoxicity of arsenic has been less well described. The aim of this review was to provide a comprehensive review of the developmental neurotoxicity of arsenic. We reviewed the published epidemiological and toxicological literature on the developmental neurotoxicity of arsenic. Arsenic is able to gain access to the developing brain and cause neurotoxic effects. Animal models link prenatal and early postnatal exposure to reduction in brain weight, reductions in numbers of glia and neurons, and alterations in neurotransmitter systems. Animal and in vitro studies both suggest that oxidative stress may be a mechanism of arsenic neurotoxicity. Fifteen epidemiological studies indicate that early life exposure is associated with deficits in intelligence and memory. These effects may occur at levels of exposure below current safety guidelines, and some neurocognitive consequences may become manifest only later in life. Sex, concomitant exposures, and timing of exposure appear to modify the developmental neurotoxicity of arsenic. Four epidemiological studies failed to show behavioral outcomes of arsenic exposure. The published literature indicates that arsenic is a human developmental neurotoxicant. Ongoing and future prospective birth cohort studies will allow more precise definition of the developmental consequences of arsenic exposure in early life. Copyright © 2014. Published by Elsevier Inc.

  3. Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Marreilha dos Santos, A.P., E-mail: apsantos@ff.ul.pt; Lucas, Rui L.; Andrade, Vanda

    2012-02-01

    Chronic, excessive exposure to manganese (Mn) may induce neurotoxicity and cause an irreversible brain disease, referred to as manganism. Efficacious therapies for the treatment of Mn are lacking, mandating the development of new interventions. The purpose of the present study was to investigate the efficacy of ebselen (Ebs) and para-aminosalicylic acid (PAS) in attenuating the neurotoxic effects of Mn in an in vivo rat model. Exposure biomarkers, inflammatory and oxidative stress biomarkers, as well as behavioral parameters were evaluated. Co-treatment with Mn plus Ebs or Mn plus PAS caused a significant decrease in blood and brain Mn concentrations (compared tomore » rats treated with Mn alone), concomitant with reduced brain E{sub 2} prostaglandin (PGE{sub 2}) and enhanced brain glutathione (GSH) levels, decreased serum prolactin (PRL) levels, and increased ambulation and rearing activities. Taken together, these results establish that both PAS and Ebs are efficacious in reducing Mn body burden, neuroinflammation, oxidative stress and locomotor activity impairments in a rat model of Mn-induced toxicity. -- Highlights: ► The manuscript is unique in its approach to the neurotoxicity of Mn. ► The manuscript incorporates molecular, cellular and functional (behavioral) analyses. ► Both PAS and Ebs are effective in restoring Mn behavioral function. ► Both PAS and Ebs are effective in reducing Mn-induced oxidative stress. ► Both PAS and Ebs led to a decrease in Mn-induced neuro-inflammation.« less

  4. Behavioral alterations of zebrafish larvae after early embryonic exposure to ketamine.

    PubMed

    Félix, Luís M; Antunes, Luís M; Coimbra, Ana M; Valentim, Ana M

    2017-02-01

    Ketamine has been associated with pediatric risks that include neurocognitive impairment and long-term behavioral disorders. However, the neurobehavioral effects of ketamine exposure in early development remain uncertain. This study aimed to test stage- and dose-dependent effects of ketamine exposure on certain brain functions by evaluating alterations in locomotion, anxiety-like and avoidance behaviors, as well as socialization. Embryos were exposed to different concentrations of ketamine (0, 0.2, 0.4, and 0.8 mg mL -1 ) for 20 min during the 256-cell (2.5 h post fertilization-hpf), 50% epiboly (5.5 hpf), and 1-4 somites (10.5 hpf) stages. General exploratory activities, natural escape-like responses, and social interactions were analyzed under continuous light or under a moving light stimulus. A dose-dependent decrease in the overall mean speed was perceived in the embryos exposed during the 256-cell stage. These results were related to previously observed head and eye malformations, following ketamine exposure at this stage and may indicate possible neurobehavioral disorders when ketamine exposure is performed at this stage. Results also showed that ketamine exposure during the 50% epiboly and 1-4 somites stages induced a significant increment of the anxiety-like behavior and a decrease in avoidance behavior in all exposed groups. Overall, the results validate the neurodevelopmental risks of early-life exposure to ketamine.

  5. Manganese in exhaled breath condensate: a new marker of exposure to welding fumes.

    PubMed

    Hulo, Sébastien; Chérot-Kornobis, Nathalie; Howsam, Mike; Crucq, Sébastien; de Broucker, Virginie; Sobaszek, Annie; Edme, Jean-Louis

    2014-04-07

    To evaluate manganese in exhaled breath condensate (Mn-EBC) as an indicator of exposure to fumes from metal inert gas welding process. We collected EBC and urine from 17 welders and 16 unexposed control subjects after 5 days exposure. Concentrations of manganese (Mn), nickel (Ni), iron (Fe) and chromium (Cr) were measured in EBC and urine samples and correlated with cumulative exposure indices for the working week (CIW) and for the total welding years (WY), based on duration of welding activity and atmospheric metal measurements. Concentrations of Mn and Ni in EBC were significantly higher among welders than controls whereas this difference was not significant for Mn in urine. Levels of Mn and Ni in EBC were not correlated with their respective levels in urine. The linear regressions found significant positive coefficients between Mn-EBC, Ni-EBC, Ni-U and Cr-U concentrations and the cumulative exposure indices. Taking into account tobacco use, statistical analysis showed the same trends except for the relationship between Mn-U and CIW. This pilot study showed that Mn-EBC, as well as Ni-EBC, can serve as reliable indices of occupational exposure to welding fumes and provide complimentary toxicokinetic information to that provided by urine analyses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. An examination of sex differences in the effects of early-life opiate and alcohol exposure

    PubMed Central

    Terasaki, Laurne S.; Gomez, Julie; Schwarz, Jaclyn M.

    2016-01-01

    Early-life exposure to drugs and alcohol is one of the most preventable causes of developmental, behavioural and learning disorders in children. Thus a significant amount of basic, animal and human research has focused on understanding the behavioural consequences and the associated neural effects of exposure to drugs and alcohol during early brain development. Despite this, much of the previous research that has been done on this topic has used predominantly male subjects or rodents. While many of the findings from these male-specific studies may ultimately apply to females, the purpose of this review is to highlight the research that has also examined sex as a factor and found striking differences between the sexes in their response to early-life opiate and alcohol exposure. Finally, we will also provide a framework for scientists interested in examining sex as a factor in future experiments that specifically examine the consequences of early-life drug and alcohol exposure. PMID:26833841

  7. Prenatal Exposure to Perfluoroalkyl Substances and Adiposity in Early and Mid-Childhood

    PubMed Central

    Mora, Ana María; Oken, Emily; Rifas-Shiman, Sheryl L.; Webster, Thomas F.; Gillman, Matthew W.; Calafat, Antonia M.; Ye, Xiaoyun; Sagiv, Sharon K.

    2016-01-01

    Background: Few studies have examined whether prenatal exposure to perfluoroalkyl substances (PFASs) is associated with childhood adiposity. Objective: We examined associations of prenatal exposure to PFASs with adiposity in early and mid-childhood. Methods: We measured plasma PFAS concentrations in 1,645 pregnant women (median, 9.6 weeks gestation) enrolled in Project Viva, a prospective pre-birth cohort study in Massachusetts (USA), between 1999 and 2002. We assessed overall and central adiposity in 1,006 children in early childhood (median, 3.2 years) and 876 in mid-childhood (median, 7.7 years) using anthropometric and dual X-ray absorptiometry (DXA) measurements. We fitted multivariable linear regression models to estimate exposure-outcome associations and evaluated effect modification by child sex. Results: Median (25–75th percentiles) prenatal plasma perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) concentrations in children assessed in early childhood were 5.6 (4.1–7.7), 24.8 (18.4–33.9), 2.4 (1.6–3.8), and 0.6 (0.5–0.9) ng/mL, respectively. Among girls, each interquartile range increment of prenatal PFOA concentrations was associated with 0.21 kg/m2 (95% CI: –0.05, 0.48) higher body mass index, 0.76 mm (95% CI: –0.17, 1.70) higher sum of subscapular and triceps skinfold thickness, and 0.17 kg/m2 (95% CI: –0.02, 0.36) higher DXA total fat mass index in mid-childhood. Similar associations were observed for PFOS, PFHxS, and PFNA. We observed null associations for boys and early-childhood adiposity measures. Conclusions: In this cohort, prenatal exposure to PFASs was associated with small increases in adiposity measurements in mid-childhood, but only among girls. Citation: Mora AM, Oken E, Rifas-Shiman SL, Webster TF, Gillman MW, Calafat AM, Ye X, Sagiv SK. 2017. Prenatal exposure to perfluoroalkyl substances and adiposity in early and mid-childhood. Environ Health

  8. Early exposure to ultraviolet-B radiation decreases immune function later in life

    PubMed Central

    Ceccato, Emma; Cramp, Rebecca L.; Seebacher, Frank; Franklin, Craig E.

    2016-01-01

    Amphibians have declined dramatically worldwide. Many of these declines are occurring in areas where no obvious anthropogenic stressors are present. It is proposed that in these areas, environmental factors such as elevated solar ultraviolet-B (UV-B) radiation could be responsible. Ultraviolet-B levels have increased in many parts of the world as a consequence of the anthropogenic destruction of the ozone layer. Amphibian tadpoles are particularly sensitive to the damaging effects of UV-B radiation, with exposure disrupting growth and fitness in many species. Given that UV-B can disrupt immune function in other animals, we tested the hypothesis that early UV-B exposure suppresses the immune responses of amphibian tadpoles and subsequent juvenile frogs. We exposed Limnodynastes peronii tadpoles to sublethal levels of UV-B radiation for 6 weeks after hatching, then examined indices of immune function in both the tadpoles and the subsequent metamorphs. There was no significant effect of UV-B on tadpole leucocyte counts or on their response to an acute antigen (phytohaemagglutinin) challenge. However, early UV-B exposure resulted in a significant reduction in both metamorph leucocyte abundance and their response to an acute phytohaemagglutinin challenge. These data demonstrate that early UV-B exposure can have carry-over effects on later life-history traits even if the applied stressor has no immediately discernible effect. These findings have important implications for our understanding of the effects of UV-B exposure on amphibian health and susceptibility to diseases such as chytridiomycosis. PMID:27668081

  9. Cognitive Function Related to Environmental Exposure to Manganese

    EPA Science Inventory

    Background: The towns of Marietta and East Liverpool (EL), Ohio, have been identified as having elevated manganese (Mn) in air due to industrial pollution. Objectives: To evaluate relationships between environmental Mn (Mn-air) exposure and distance from the source and cognitive...

  10. Environmental exposure to manganese in air: Associations with tremor and motor function.

    PubMed

    Bowler, Rosemarie M; Beseler, Cheryl L; Gocheva, Vihra V; Colledge, Michelle; Kornblith, Erica S; Julian, Jaime R; Kim, Yangho; Bollweg, George; Lobdell, Danelle T

    2016-01-15

    Manganese (Mn) inhalation has been associated with neuropsychological and neurological sequelae in exposed workers. Few environmental epidemiologic studies have examined the potentially neurotoxic effects of Mn exposure in ambient air on motor function and hand tremor in adult community residents. Mn exposed residents were recruited in two Ohio towns: Marietta, a town near a ferro-manganese smelter, and East Liverpool, a town adjacent to a facility processing, crushing, screening, and packaging Mn products. Chronic (≥ 10 years) exposure to ambient air Mn in adult residents and effects on neuropsychological and neurological outcomes were investigated. Participants from Marietta (n=100) and East Liverpool (n=86) were combined for analyses. AERMOD dispersion modeling of fixed-site outdoor air monitoring data estimated Mn inhalation over a ten year period. Adult Mn-exposed residents' psychomotor ability was assessed using Finger Tapping, Hand Dynamometer, Grooved Pegboard, and the Computerized Adaptive Testing System (CATSYS) Tremor system. Bayesian structural equation modeling was used to assess associations between air-Mn and motor function and tremor. Air-Mn exposure was significantly correlated in bivariate analyses with the tremor test (CATSYS) for intensity, center frequency and harmonic index. The Bayesian path analysis model showed associations of air-Mn with the CATSYS non-dominant center frequency and harmonic index; while the Bayesian structural equation model revealed associations between air-Mn and lower Finger Tapping scores. Household income was significantly associated with motor dysfunction but not with tremor. Tremor and motor function were associated with higher exposure to airborne Mn. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. The Contribution of M.N. Skatkin to the Advancement of Didactic Ideas about the Developmental Role of Education (1950s to Early 1960s)

    ERIC Educational Resources Information Center

    Selivyorstova, E. N.

    2015-01-01

    The article analyzes the research that M.N. Skatkin conducted during the 1950s and early 1960s and describes its contribution to the elabortion of Russian teaching science approaches towards understanding of the developmental role of education. [This article was translated by Kenneth Cargill.

  12. Antibiotic Exposure in Early Life Increases Risk of Childhood Obesity: A Systematic Review and Meta-Analysis

    PubMed Central

    Shao, Xiaoqing; Ding, Xiaolian; Wang, Bin; Li, Ling; An, Xiaofei; Yao, Qiuming; Song, Ronghua; Zhang, Jin-an

    2017-01-01

    A number of studies have previously assessed the impact of antibiotic exposure in early life on the risk of childhood obesity, but no systematic assessment is currently available. A systematic review and meta-analysis was performed to comprehensively and quantitatively elucidate the risk of childhood obesity caused by antibiotic exposure in early life. Literature search was performed in PubMed, Embase, and Web of Science. Random-effect meta-analysis was used to pool the statistical estimates. Fifteen cohort studies involving 445,880 participants were finally included, and all those studies were performed in developed countries. Antibiotic exposure in early life significantly increased risk of childhood overweight [relative risk (RR) = 1.23, 95% confidence interval (CI) 1.13–1.35, P < 0.001] and childhood obesity (RR = 1.21, 95% CI 1.13–1.30, P < 0.001). Antibiotic exposure in early life also significantly increased the z-score of childhood body mass index (mean difference: 0.07, 95% CI 0.05–0.09, P < 0.00001). Importantly, there was an obvious dose–response relationship between antibiotic exposure in early life and childhood adiposity, with a 7% increment in the risk of overweight (RR = 1.07, 95% CI 1.01–1.15, P = 0.03) and a 6% increment in the risk of obesity (RR = 1.06, 95% CI 1.02–1.09, P < 0.001) for each additional course of antibiotic exposure. In conclusion, antibiotic exposure in early life significantly increases risk of childhood obesity. Moreover, current analyses are mainly taken from developed countries, and therefore the impact of antibiotic exposure on risk of childhood obesity in vulnerable populations or developing countries still needs to be evaluated in future studies. PMID:28775712

  13. The role of marine biotoxins on the trophic transfer of Mn and Zn in fish.

    PubMed

    Pouil, Simon; Clausing, Rachel J; Metian, Marc; Bustamante, Paco; Dechraoui Bottein, Marie-Yasmine

    2018-05-01

    Essential nutrients are critical for physiological processes of organisms. In fish, they are obtained primarily from the diet, and their transfer and accumulation are known to be impacted by environmental variables such as water temperature, pH and salinity, as well as by diet composition and matrices. Yet, prey items consumed by fish may also contain toxic compounds such as marine toxins associated with harmful algae. These biotoxins have the potential to affect essential trace element assimilation in fish through chemical interactions such as the formation of trace element-toxin complexes or by affecting general fish physiology as in the modification of ion-specific transport pathways. We assessed the influence of dietary exposure to brevetoxins (PbTxs), ichthyotoxic neurotoxins produced by the dinoflagellate Karenia brevis, on trophic transfer of two essential trace elements, Mn and Zn, in a fish model. Using ecologically relevant concentrations of PbTxs and trace elements in controlled laboratory conditions, juvenile turbots Scophthalmus maximus were given food containing PbTxs before or at the same time as a feeding with radiotracers of the chosen essential elements ( 54 Mn and 65 Zn). Treatments included simultaneous exposure (PbTxs +  54 Mn +  65 Zn) in a single-feeding, 3-week daily pre-exposure to dietary PbTx followed by a single feeding with 54 Mn and 65 Zn, and a control ( 54 Mn and 65 Zn only). After a 21-day depuration period, turbot tissue brevetoxin levels were quantified and assimilation efficiencies of 54 Mn and 65 Zn were assessed. PbTxs were found in turbot tissues in each exposure treatment, demonstrating dietary trophic transfer of these toxins; yet, no differences in assimilation efficiencies of Mn or Zn were found between treatments or the control (p > 0.05). These results indicate that, in our experimental conditions, PbTx exposure does not significantly affect the trophic transfer of Mn and Zn in fish. Copyright © 2018

  14. Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps

    PubMed Central

    Bailey, Kathryn A.; Smith, Allan H.; Tokar, Erik J.; Graziano, Joseph H.; Kim, Kyoung-Woong; Navasumrit, Panida; Ruchirawat, Mathuros; Thiantanawat, Apinya; Suk, William A.; Fry, Rebecca C.

    2015-01-01

    Background Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. Objectives This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. Discussion Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. Conclusions Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes. Citation Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360 PMID:26115410

  15. CONSEQUENCES OF REPEATED ETHANOL EXPOSURE DURING EARLY OR LATE ADOLESCENCE ON CONDITIONED TASTE AVERSIONS IN RATS

    PubMed Central

    Saalfield, Jessica; Spear, Linda

    2015-01-01

    Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences.. Recent evidence suggests that adolescents are less sensitive than adults to ethanol’s aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4 g/kg i.g. ethanol (25%) or water every 48 hours from postnatal day (P) 25–45 (early AIE) or P45–65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5 g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence. PMID:25698309

  16. Exposure to dim light at night during early development increases adult anxiety-like responses.

    PubMed

    Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J

    2014-06-22

    Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior

  17. Quartz exposure, retention, and early silicosis in sheep.

    PubMed

    Bégin, R; Dufresne, A; Cantin, A; Possmayer, F; Sébastien, P; Fabi, D; Bilodeau, G; Martel, M; Bisson, D; Pietrowski, B

    1989-05-01

    The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To

  18. Exposure to Childhood Sexual and Physical Abuse and Adjustment in Early Adulthood

    ERIC Educational Resources Information Center

    Fergusson, David M.; Boden, Joseph M.; Horwood, L. John

    2008-01-01

    Objective: This research examined linkages between exposure to childhood sexual abuse (CSA) and childhood physical punishment/abuse (CPA) and mental health issues in early adulthood. Method: The investigation analyzed data from a birth cohort of over 1,000 New Zealand young adults studied to the age of 25. Results: Exposure to CSA and CPA was…

  19. Early life exposure to malaria and cognition in adulthood: evidence from Mexico.

    PubMed

    Venkataramani, Atheendar S

    2012-09-01

    This study examines the impact of early life malaria exposure on cognition in sample of Mexican adults, using the nationwide introduction of malaria eradication efforts to identify causal impacts. The core findings are that birth year exposure to malaria eradication was associated with increases in Raven Progressive Matrices test scores and consumption expenditures, but not schooling. Additionally, cohorts born after eradication both entered and exited school earlier than their pre-eradication counterparts. These effects were only seen for men and explanations for this are assessed. Collectively, these findings suggest that improvements in infant health help explain secular increases in cognitive test scores, that better cognition may link early life health to adulthood earnings, and that human capital investments through childhood and young adulthood respond sensitively to market returns to early life endowment shocks. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats.

    PubMed

    Saalfield, Jessica; Spear, Linda

    2015-12-01

    Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4g/kg i.g. ethanol (25%) or water every 48 h from postnatal day (P) 25-45 (early AIE) or P45-65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Levels and predictors of airborne and internal exposure to manganese and iron among welders.

    PubMed

    Pesch, Beate; Weiss, Tobias; Kendzia, Benjamin; Henry, Jana; Lehnert, Martin; Lotz, Anne; Heinze, Evelyn; Käfferlein, Heiko Udo; Van Gelder, Rainer; Berges, Markus; Hahn, Jens-Uwe; Mattenklott, Markus; Punkenburg, Ewald; Hartwig, Andrea; Brüning, Thomas

    2012-01-01

    We investigated airborne and internal exposure to manganese (Mn) and iron (Fe) among welders. Personal sampling of welding fumes was carried out in 241 welders during a shift. Metals were determined by inductively coupled plasma mass spectrometry. Mn in blood (MnB) was analyzed by graphite furnace atom absorption spectrometry. Determinants of exposure levels were estimated with multiple regression models. Respirable Mn was measured with a median of 62 (inter-quartile range (IQR) 8.4-320) μg/m(3) and correlated with Fe (r=0.92, 95% CI 0.90-0.94). Inhalable Mn was measured with similar concentrations (IQR 10-340 μg/m(3)). About 70% of the variance of Mn and Fe could be explained, mainly by the welding process. Ventilation decreased exposure to Fe and Mn significantly. Median concentrations of MnB and serum ferritin (SF) were 10.30 μg/l (IQR 8.33-13.15 μg/l) and 131 μg/l (IQR 76-240 μg/l), respectively. Few welders were presented with low iron stores, and MnB and SF were not correlated (r=0.07, 95% CI -0.05 to 0.20). Regression models revealed a significant association of the parent metal with MnB and SF, but a low fraction of variance was explained by exposure-related factors. Mn is mainly respirable in welding fumes. Airborne Mn and Fe influenced MnB and SF, respectively, in welders. This indicates an effect on the biological regulation of both metals. Mn and Fe were strongly correlated, whereas MnB and SF were not, likely due to higher iron stores among welders.

  2. Childhood Exposure to Manganese and Postural Instability in Children living near a Ferromanganese Refinery in Southeastern Ohio

    PubMed Central

    Rugless, Fedoria; Bhattacharya, Amit; Succop, Paul; Dietrich, Kim N.; Cox, Cyndy; Alden, Jody; Kuhnell, Pierce; Barnas, Mary; Wright, Robert; Parsons, Patrick J.; Praamsma, Meredith L.; Palmer, Christopher D.; Beidler, Caroline; Wittberg, Richard; Haynes, Erin N.

    2014-01-01

    Airborne manganese (Mn) exposure can result in neurotoxicity and postural instability in occupationally exposed workers, yet few studies have explored the association ambient exposure to Mn in children and postural stability. The goal of this study was to determine the association between Mn and lead (Pb) exposure, as measured by blood Pb, blood and hair Mn and time weighted distance (TWD) from a ferromanganese refinery, and postural stability in children. A subset of children ages 7–9 years enrolled in the Marietta Community Actively Researching Exposure Study (CARES) were invited to participate. Postural balance was conducted on 55 children residing in Marietta, Ohio and the surrounding area. Samples of blood were collected and analyzed for Mn and Pb, and samples of hair were analyzed for Mn. Neuromotor performance was assessed using postural balance testing with a computer force platform system. Pearson correlations were calculated to identify key covariates. Associations between postural balance testing conditions and Mn and Pb exposure were estimated with linear regression analyses adjusting for gender, age, parent IQ, parent age. Mean blood Mn was 10 μg/L (SEM=0.36), mean blood Pb was 0.85 μg/dL (SEM=0.05), and mean hair Mn was 0.76 μg/g (SEM=0.16). Mean residential distance from the refinery was 11.5 km (SEM=0.46). All three measures of Mn exposure were significantly associated with poor postural balance. In addition, low-level blood Pb was also negatively associated with balance outcomes. We conclude that Mn exposure and low-level blood Pb are significantly associated with poor postural balance. PMID:24370548

  3. Early-life bisphenol a exposure and child body mass index: a prospective cohort study.

    PubMed

    Braun, Joseph M; Lanphear, Bruce P; Calafat, Antonia M; Deria, Sirad; Khoury, Jane; Howe, Chanelle J; Venners, Scott A

    2014-11-01

    Early-life exposure to bisphenol A (BPA) may increase childhood obesity risk, but few prospective epidemiological studies have investigated this relationship. We sought to determine whether early-life exposure to BPA was associated with increased body mass index (BMI) at 2-5 years of age in 297 mother-child pairs from Cincinnati, Ohio (HOME Study). Urinary BPA concentrations were measured in samples collected from pregnant women during the second and third trimesters and their children at 1 and 2 years of age. BMI z-scores were calculated from weight/height measures conducted annually from 2 through 5 years of age. We used linear mixed models to estimate BMI differences or trajectories with increasing creatinine-normalized BPA concentrations. After confounder adjustment, each 10-fold increase in prenatal (β = -0.1; 95% CI: -0.5, 0.3) or early-childhood (β = -0.2; 95% CI: -0.6, 0.1) BPA concentrations was associated with a modest and nonsignificant reduction in child BMI. These inverse associations were suggestively stronger in girls than in boys [prenatal effect measure modification (EMM) p-value = 0.30, early-childhood EMM p-value = 0.05], but sex-specific associations were imprecise. Children in the highest early-childhood BPA tercile had lower BMI at 2 years (difference = -0.3; 95% CI: -0.6, 0.0) and larger increases in their BMI slope from 2 through 5 years (BMI increase per year = 0.12; 95% CI: 0.07, 0.18) than children in the lowest tercile (BMI increase per year = 0.07; 95% CI: 0.01, 0.13). All associations were attenuated without creatinine normalization. Prenatal and early-childhood BPA exposures were not associated with increased BMI at 2-5 years of age, but higher early-childhood BPA exposures were associated with accelerated growth during this period.

  4. Childhood developmental vulnerabilities associated with early life exposure to infectious and noninfectious diseases and maternal mental illness.

    PubMed

    Green, Melissa J; Kariuki, Maina; Dean, Kimberlie; Laurens, Kristin R; Tzoumakis, Stacy; Harris, Felicity; Carr, Vaughan J

    2017-12-26

    Fetal exposure to infectious and noninfectious diseases may influence early childhood developmental functioning, on the path to later mental illness. Here, we investigated the effects of in utero exposure to maternal infection and noninfectious diseases during pregnancy on offspring developmental vulnerabilities at age 5 years, in the context of estimated effects for early childhood exposures to infectious and noninfectious diseases and maternal mental illness. We used population data for 66,045 children from an intergenerational record linkage study (the New South Wales Child Development Study), for whom a cross-sectional assessment of five developmental competencies (physical, social, emotional, cognitive, and communication) was obtained at school entry, using the Australian Early Development Census (AEDC). Child and maternal exposures to infectious or noninfectious diseases were determined from the NSW Ministry of Health Admitted Patients Data Collection (APDC) and maternal mental illness exposure was derived from both APDC and Mental Health Ambulatory Data collections. Multinomial logistic regression analyses were used to examine unadjusted and adjusted associations between these physical and mental health exposures and child developmental vulnerabilities at age 5 years. Among the physical disease exposures, maternal infectious diseases during pregnancy and early childhood infection conferred the largest associations with developmental vulnerabilities at age 5 years; maternal noninfectious illness during pregnancy also retained small but significant associations with developmental vulnerabilities even when adjusted for other physical and mental illness exposures and covariates known to be associated with early childhood development (e.g., child's sex, socioeconomic disadvantage, young maternal age, prenatal smoking). Among all exposures examined, maternal mental illness first diagnosed prior to childbirth conferred the greatest odds of developmental

  5. Programming social, cognitive, and neuroendocrine development by early exposure to novelty.

    PubMed

    Tang, Akaysha C; Akers, Katherine G; Reeb, Bethany C; Romeo, Russell D; McEwen, Bruce S

    2006-10-17

    Mildly stressful early life experiences can potentially impact a broad range of social, cognitive, and physiological functions in humans, nonhuman primates, and rodents. Recent rodent studies favor a maternal-mediation hypothesis that considers maternal-care differences induced by neonatal stimulation as the cause of individual differences in offspring development. Using neonatal novelty exposure, a neonatal stimulation paradigm that dissociates maternal individual differences from a direct stimulation effect on the offspring, we investigated the effect of early exposures to novelty on a diverse range of psychological functions using several assessment paradigms. Pups that received brief neonatal novelty exposures away from the home environment showed enhancement in spatial working memory, social competition, and corticosterone response to surprise during adulthood compared with their home-staying siblings. These functional enhancements in novelty-exposed rats occurred despite evidence that maternal care was directed preferentially toward home-staying instead of novelty-exposed pups, indicating that greater maternal care is neither necessary nor sufficient for these early stimulation-induced functional enhancements. We suggest a unifying maternal-modulation hypothesis, which distinguishes itself from the maternal-mediation hypothesis in that (i) neonatal stimulation can have direct effects on pups, cumulatively leading to long-term improvement in adult offspring; and (ii) maternal behavior can attenuate or potentiate these effects, thereby decreasing or increasing this long-term functional improvement.

  6. Exposure to dust mite allergen and endotoxin in early life and asthma and atopy in childhood

    PubMed Central

    Celedón, Juan C.; Milton, Donald K.; Ramsey, Clare D.; Litonjua, Augusto A.; Ryan, Louise; Platts-Mills, Thomas A. E.; Gold, Diane R.

    2013-01-01

    Background There has been no longitudinal study of the relation between concurrent exposure to dust mite allergen and endotoxin in early life and asthma and atopy at school age. Objectives To examine the relation between exposure to dust mite allergen and endotoxin at age 2 to 3 months and asthma, wheeze, and atopy in high-risk children. Methods Birth cohort study of 440 children with parental history of atopy in the Boston metropolitan area. Results In multivariate analyses, early exposure to high levels of dust mite allergen (≥10 μg/g) was associated with increased risks of asthma at age 7 years (odds ratio [OR], 3.0; 95% CI, 1.1-7.9) and late-onset wheeze (OR, 5.0; 95% CI, 1.5-16.4). Exposure to endotoxin levels above the lowest quartile at age 2 to 3 months was associated with reduced odds of atopy at school age (OR, 0.5; 95% CI, 0.2-0.9). In contrast with its inverse association with atopy, endotoxin exposure in early life was associated with an increased risk of any wheeze between ages 1 and 7 years that did not change significantly with time (hazard ratio for each quartile increment in endotoxin levels, 1.23; 95% CI, 1.07-1.43). Conclusion Among children at risk of atopy, early exposure to high levels of dust mite allergen is associated with increased risks of asthma and late-onset wheeze. In these children, endotoxin exposure is associated with a reduced risk of atopy but an increased risk of wheeze. Clinical implications Early endotoxin exposure may be a protective factor against atopy but a risk factor for wheeze in high-risk children. PMID:17507083

  7. Prenatal and Early Childhood Exposure to Tetrachloroethylene and Adult Vision

    PubMed Central

    Getz, Kelly D.; Janulewicz, Patricia A.; Rowe, Susannah; Weinberg, Janice M.; Winter, Michael R.; Martin, Brett R.; Vieira, Veronica M.; White, Roberta F.

    2012-01-01

    Background: Tetrachloroethylene (PCE; or perchloroethylene) has been implicated in visual impairments among adults with occupational and environmental exposures as well as children born to women with occupational exposure during pregnancy. Objectives: Using a population-based retrospective cohort study, we examined the association between prenatal and early childhood exposure to PCE-contaminated drinking water on Cape Cod, Massachusetts, and deficits in adult color vision and contrast sensitivity. Methods: We estimated the amount of PCE that was delivered to the family residence from participants’ gestation through 5 years of age. We administered to this now adult study population vision tests to assess acuity, contrast sensitivity, and color discrimination. Results: Participants exposed to higher PCE levels exhibited lower contrast sensitivity at intermediate and high spatial frequencies compared with unexposed participants, although the differences were generally not statistically significant. Exposed participants also exhibited poorer color discrimination than unexposed participants. The difference in mean color confusion indices (CCI) was statistically significant for the Farnsworth test but not Lanthony’s D-15d test [Farnsworth CCI mean difference = 0.05, 95% confidence interval (CI): 0.003, 0.10; Lanthony CCI mean difference = 0.07, 95% CI: –0.02, 0.15]. Conclusions: Prenatal and early childhood exposure to PCE-contaminated drinking water may be associated with long-term subclinical visual dysfunction in adulthood, particularly with respect to color discrimination. Further investigation of this association in similarly exposed populations is necessary. PMID:22784657

  8. Prenatal and Early Life Exposure to Traffic Pollution and Cardiometabolic Health in Childhood

    PubMed Central

    Fleisch, Abby F.; Luttmann-Gibson, Heike; Perng, Wei; Rifas-Shiman, Sheryl L.; Coull, Brent A.; Kloog, Itai; Koutrakis, Petros; Schwartz, Joel D.; Zanobetti, Antonella; Mantzoros, Christos S.; Gillman, Matthew W.; Gold, Diane R.; Oken, Emily

    2016-01-01

    Background Prenatal exposure to traffic pollution has been associated with faster infant weight gain, but implications for cardiometabolic health in later childhood are unknown. Methods Among 1,418 children in Project Viva, a Boston-area pre-birth cohort, we assessed anthropometric and biochemical parameters of cardiometabolic health in early (median age 3.3 years) and mid- (median age 7.7 years) childhood. We used spatiotemporal models to estimate prenatal and early life residential PM2.5 and black carbon exposure as well as traffic density and roadway proximity. We performed linear regression analyses adjusted for sociodemographics Results Children whose mothers lived close to a major roadway at the time of delivery had higher markers of adverse cardiometabolic risk in early and mid-childhood. For example, total fat mass was 2.1kg (95%CI: 0.8, 3.5) higher in mid-childhood for children of mothers who lived < 50 m vs. ≥ 200m from a major roadway. Black carbon exposure and traffic density were generally not associated with cardiometabolic parameters, and PM2.5 exposure during the year prior was paradoxically associated with improved cardiometabolic profile Conclusions Infants whose mothers lived close to a major roadway at the time of delivery may be at later risk for adverse cardiometabolic health. PMID:26843357

  9. Stress Induced Charge-Ordering Process in LiMn 2O 4

    DOE PAGES

    Chen, Yan; Yu, Dunji; An, Ke

    2016-07-25

    In this letter we report the stress-induced Mn charge-ordering process in the LiMn 2O 4 spinel, evidenced by the lattice strain evolutions due to the Jahn–Teller effects. In situ neutron diffraction reveals the initial stage of this process at low stress, indicating the eg electron localization at the preferential Mn sites during the early phase transition as an underlying charge-ordering mechanism in the charge-frustrated LiMn 2O 4. The initial stage of this transition exhibits as a progressive lattice and charge evolution, without showing a first-order behavior.

  10. Early Programming of Uterine Tissue by Bisphenol A: Critical Evaluation of Evidence from Animal Exposure Studies

    PubMed Central

    Suvorov, Alexander; Waxman, David J.

    2015-01-01

    Exposure to Bisphenol A (BPA) during the critical window of uterine development has been proposed to program the uterus for increased disease susceptibility based on well-documented effects of the potent xenoestrogen diethylstilbestrol. To investigate this proposal, we reviewed 37 studies of prenatal and/or perinatal BPA exposure in animal models and evaluated evidence for: molecular signatures of early BPA exposure; the development of adverse uterine health effects; and epigenetic changes linked to long-term dysregulation of uterine gene expression and health effects. We found substantial evidence for adult uterine effects of early BPA exposure. In contrast, experimental support for epigenetic actions of early BPA exposure is very limited, and largely consists of effects on Hoxa gene DNA methylation. Critical knowledge gaps were identified, including the need to fully characterize short-term and long-term uterine gene responses, interactions with estrogens and other endogenous hormones, and any long-lasting epigenetic signatures that impact adult disease. PMID:26028543

  11. Exposure to Alcohol Content in Movies and Initiation of Early Drinking Milestones.

    PubMed

    Jackson, Kristina M; Janssen, Tim; Barnett, Nancy P; Rogers, Michelle L; Hayes, Kerri L; Sargent, James

    2018-01-01

    Exposure to alcohol content in movies has been shown to be associated with adolescent use of alcohol, including earlier onset. This study examined the influence of movie alcohol exposure on subsequent alcohol onset, considering the social context (whether the movie was viewed with a friend or parent). We examined whether media's influence holds across a spectrum of early drinking milestones: sipping (but not consuming a full drink of) alcohol, consuming a full drink of alcohol, and engaging in heavy episodic drinking (HED). Data were taken from a sample of 882 middle school youth (52% female; 24% non-White) enrolled in an ongoing study on alcohol initiation and progression. Exposure to alcohol content in films was measured using a method that combines content analysis and random assignment of movie titles to youth surveys. The hazard of initiating alcohol use (sip, full drink, HED) as a function of exposure was estimated using survival analysis. Associations were adjusted for demographic, personality, and social influence factors known to be associated with both movie exposure and alcohol use. Exposure to alcohol content was common. Hours of exposure prospectively predicted earlier onset of alcohol involvement across all outcomes. Viewing movies with friends appeared to augment the media exposure effect, in contrast to viewing movies with parents, which was not a significant predictor of initiation. Exposure to alcohol in films is involved in the entry into early stages of alcohol involvement. Findings support further investigation into the role of the media in underage drinking, especially in the context of consuming media with friends and peers. Limiting media exposure and/or stronger Federal Trade Commission oversight of movie ratings should be a priority for preventing underage drinking. Copyright © 2017 by the Research Society on Alcoholism.

  12. Variance components of short-term biomarkers of manganese exposure in an inception cohort of welding trainees.

    PubMed

    Baker, Marissa G; Simpson, Christopher D; Sheppard, Lianne; Stover, Bert; Morton, Jackie; Cocker, John; Seixas, Noah

    2015-01-01

    Various biomarkers of exposure have been explored as a way to quantitatively estimate an internal dose of manganese (Mn) exposure, but given the tight regulation of Mn in the body, inter-individual variability in baseline Mn levels, and variability in timing between exposure and uptake into various biological tissues, identification of a valuable and useful biomarker for Mn exposure has been elusive. Thus, a mixed model estimating variance components using restricted maximum likelihood was used to assess the within- and between-subject variance components in whole blood, plasma, and urine (MnB, MnP, and MnU, respectively) in a group of nine newly-exposed apprentice welders, on whom baseline and subsequent longitudinal samples were taken over a three month period. In MnB, the majority of variance was found to be between subjects (94%), while in MnP and MnU the majority of variance was found to be within subjects (79% and 99%, respectively), even when controlling for timing of sample. While blood seemed to exhibit a homeostatic control of Mn, plasma and urine, with the majority of the variance within subjects, did not. Results presented here demonstrate the importance of repeat measure or longitudinal study designs when assessing biomarkers of Mn, and the spurious associations that could result from cross-sectional analyses. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. Exposure to Violence Predicting Cortisol Response During Adolescence and Early Adulthood: Understanding Moderating Factors

    PubMed Central

    Heinze, Justin E.; Miller, Alison L.; Stoddard, Sarah A.; Zimmerman, Marc A.

    2014-01-01

    Previous research on the association between violence and biological stress regulation has been largely cross-sectional, and has also focused on childhood. Using longitudinal data from a low-income, high-risk, predominantly African-American sample (n = 266; 57 % female), we tested hypotheses about the influence of cumulative exposure to violence during adolescence and early adulthood on cortisol responses in early adulthood. We found that cumulative exposure to violence predicted an attenuated cortisol response. Further, we tested whether sex, mothers’ support, or fathers’ support moderated the effect of exposure to violence on cortisol responses. We found that the effect of cumulative exposure to violence on cortisol was modified by sex; specifically, males exposed to violence exhibited a more attenuated response pattern. In addition, the effect of cumulative exposure to violence on cortisol was moderated by the presence of fathers’ support during adolescence. The findings contribute to a better understanding of how cumulative exposure to violence influences biological outcomes, emphasizing the need to understand sex and parental support as moderators of risk. PMID:24458765

  14. Family Instability and Exposure to Violence in the Early Life Course.

    PubMed

    Cavanagh, Shannon E; Stritzel, Haley; Smith, Chelsea; Crosnoe, Robert

    2017-10-11

    Family instability has been linked with a host of outcomes across the early life course. This study extends this literature by connecting instability with violence in the community by examining the associations among family structure, family structure change, and secondary exposure to violence during adolescence across diverse segments of the population. Using longitudinal data from the Project on Human Development in Chicago Neighborhoods study, we found that living with a single parent and experiencing family structure changes were associated with secondary exposure to violence. Multiple group models suggest that partner change translated into more exposure for boys than girls. Findings also suggest that family instability may lead to more secondary exposure to violence for African American youth. © 2017 Society for Research on Adolescence.

  15. Triple-mixture of Zn, Mn, and Fe increases bioaccumulation and causes oxidative stress in freshwater neotropical fish.

    PubMed

    de Oliveira, Luciana Fernandes; Santos, Caroline; Risso, Wagner Ezequiel; Dos Reis Martinez, Claudia Bueno

    2018-06-01

    Metal bioaccumulation and oxidative stress biomarkers were determined in Prochilodus lineatus to understand the effects of short-term exposure to a triple-mixture of Zn, Mn, and Fe. Three independent tests were carried out, in which fish were exposed to 3 concentrations of Zn (0.18, 1.0, and 5.0 mg L -1 ), Mn (0.1, 0.5, and 5.0 mg L -1 ), and in the mix test to Fe (5.0 mg L -1 ) and a mixture of Zn (1.0 mg L -1 ) + Mn (0.5 mg L -1 ), with and without Fe. After exposure for 96 h, tissues were removed for metal bioaccumulation analysis and oxidative stress biomarkers were determined in liver, along with DNA damage in blood cells. Our results revealed that Zn and Mn were bioaccumulated in fish tissues after exposure to 5.0 mg L -1 , whereas Fe only bioaccumulated in muscle and gills after mixture exposure. Results indicated that 1 metal interfered with the other's bioaccumulation. In P. lineatus, 5 mg L -1 of both Mn and Fe were toxic, because damage was observed (lipid peroxidation [LPO] in liver and DNA damage in blood cells), whereas Zn induced liver responses (metallothionein [MT] and reduced glutathione [GSH] increases) to prevent damage. In terms of bioaccumulation and alterations of oxidative stress biomarkers, we showed that Zn, Mn, and Fe triple-mixture enhances individual metal toxicity in Neotropical fish P. lineatus. Environ Toxicol Chem 2018;37:1749-1756. © 2018 SETAC. © 2018 SETAC.

  16. Activation of a water molecule using a mononuclear Mn complex: from Mn-aquo, to Mn-hydroxo, to Mn-oxyl via charge compensation.

    PubMed

    Lassalle-Kaiser, Benedikt; Hureau, Christelle; Pantazis, Dimitrios A; Pushkar, Yulia; Guillot, Régis; Yachandra, Vittal K; Yano, Junko; Neese, Frank; Anxolabéhère-Mallart, Elodie

    2010-07-01

    Activation of a water molecule by the electrochemical oxidation of a Mn-aquo complex accompanied by the loss of protons is reported. The sequential (2 × 1 electron/1 proton) and direct (2 electron/2 proton) proton-coupled electrochemical oxidation of a non-porphyrinic six-coordinated Mn(II)OH 2 complex into a mononuclear Mn(O) complex is described. The intermediate Mn(III)OH 2 and Mn(III)OH complexes are electrochemically prepared and analysed. Complete deprotonation of the coordinated water molecule in the Mn(O) complex is confirmed by electrochemical data while the analysis of EXAFS data reveals a gradual shortening of an Mn-O bond upon oxidation from Mn(II)OH 2 to Mn(III)OH and Mn(O). Reactivity experiments, DFT calculations and XANES pre-edge features provide strong evidence that the bonding in Mn(O) is best characterized by a Mn(III)-oxyl description. Such oxyl species could play a crucial role in natural and artificial water splitting reactions. We provide here a synthetic example for such species, obtained by electrochemical activation of a water ligand.

  17. Exploring Manganese Fractionation Using a Sequential Extraction Method to Evaluate Welders' Gas Metal Arc Welding Exposures during Heavy Equipment Manufacturing.

    PubMed

    Hanley, Kevin W; Andrews, Ronnee; Bertke, Steven; Ashley, Kevin

    2017-01-01

    The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in welding fume at three factories where heavy equipment was manufactured. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. One hundred nine worker-days were monitored for either total or respirable Mn during gas metal arc welding. The samples were analyzed using an experimental method to separate different Mn fractions based on selective chemical solubility. The full-shift total particle size Mn time-weighted average (TWA) breathing zone concentrations ranged 0.38-26 for soluble Mn in a mild ammonium acetate solution; 3.2-170 for Mn0,2+ in acetic acid; 3.1-290 for Mn3+,4+ in hydroxylamine-hydrochloride; and non-detectable (ND)-130 µg m-3 for insoluble Mn fractions in hydrochloric and nitric acid. The summation of all the total particulate Mn TWA fractions yielded results that ranged from 6.9 to 610 µg m-3. The range of respirable size Mn TWA concentrations were 0.33-21 for soluble Mn; 15-140 for Mn0,2+; 14-170 for Mn3+,4+; 5.3-230 for insoluble Mn; and 36-530 µg m-3 for Mn (sum of fractions). Total particulate TWA GM concentrations of the Mn (sum) were 53 (GSD = 2.5), 150 (GSD = 1.7), and 120 (GSD = 1.8) µg m-3 for the three separate factories. Although all of the workers' exposures were measured below the OSHA regulatory permissible exposure limit and NIOSH recommended exposure limit for Mn, 70 welders' exposures exceeded the ACGIH Threshold Limit Values® for total Mn (100 µg m-3) and 29 exceeded the recently adopted respirable Mn TLV (20 µg m-3). This study shows that a welding fume exposure control and management program is warranted for Mn, which includes improved exhaust ventilation and may necessitate the use of respiratory protection, especially for welding parts that impede air circulation. Published by Oxford University Press on behalf of

  18. Bias to pollen odors is affected by early exposure and foraging experience.

    PubMed

    Arenas, A; Farina, W M

    2014-07-01

    In many pollinating insects, foraging preferences are adjusted on the basis of floral cues learned at the foraging site. In addition, olfactory experiences gained at early adult stages might also help them to initially choose food sources. To understand pollen search behavior of honeybees, we studied how responses elicited by pollen-based odors are biased in foraging-age workers according to (i) their genetic predisposition to collect pollen, (ii) pollen related information gained during foraging and (iii) different experiences with pollen gained at early adult ages. Bees returning to the hive carrying pollen loads, were strongly biased to unfamiliar pollen bouquets when tested in a food choice device against pure odors. Moreover, pollen foragers' orientation response was specific to the odors emitted by the pollen type they were carrying on their baskets, which suggests that foragers retrieve pollen odor information to recognize rewarding flowers outside the hive. We observed that attraction to pollen odor was mediated by the exposure to a pollen diet during the first week of life. We did not observe the same attraction in foraging-age bees early exposed to an artificial diet that did not contain pollen. Contrary to the specific response observed to cues acquired during foraging, early exposure to single-pollen diets did not bias orientation response towards a specific pollen odor in foraging-age bees (i.e. bees chose equally between the exposed and the novel monofloral pollen odors). Our results show that pollen exposure at early ages together with olfactory experiences gained in a foraging context are both relevant to bias honeybees' pollen search behavior. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Effects of Long-Term Exposure to Zinc Oxide Nanoparticles on Development, Zinc Metabolism and Biodistribution of Minerals (Zn, Fe, Cu, Mn) in Mice

    PubMed Central

    Wang, Chao; Lu, Jianjun; Zhou, Le; Li, Jun; Xu, Jiaman; Li, Weijian; Zhang, Lili; Zhong, Xiang; Wang, Tian

    2016-01-01

    Zinc oxide nanoparticles (nano-ZnOs) are widely used and possess great potentials in agriculture and biomedicine. It is inevitable for human exposure to these nanoparticles. However, no study had been conducted to investigate the long term effects of nano-ZnOs. This study aimed at investigating effects of nano-ZnOs on development, zinc metabolism and biodistribution of minerals (Zn, Fe, Cu, and Mn) in mice from week 3 to 35. After the characteristics of nano-ZnOs were determined, they were added into the basal diet at 0, 50, 500 and 5000 mg/kg. Results indicated that added 50 and 500 mg/kg nano-ZnOs showed minimal toxicity. However, 5000 mg/kg nano-ZnOs significantly decreased body weight (from week 4 to 16) and increased the relative weights of the pancreas, brain and lung. Added 5000 mg/kg nano-ZnOs significantly increased the serum glutamic-pyruvic transaminase activity and zinc content, and significantly enhanced mRNA expression of zinc metabolism-related genes, including metallothionein 1(32.66 folds), metallothionein 2 (31.42 folds), ZIP8 (2.21folds), ZIP14 (2.45 folds), ZnT1 (4.76 folds), ZnT2 (6.19 folds) and ZnT4 (1.82 folds). The biodistribution determination showed that there was a significant accumulation of zinc in the liver, pancreas, kidney, and bones (tibia and fibula) after receiving 5000 mg/kg nano-ZnO diet, while no significant effects on Cu, Fe, and Mn levels, except for liver Fe content and pancreas Mn level. Our results demonstrated that long term exposure to 50 and 500 mg/kg nano-ZnO diets showed minimal toxicity. However, high dose of nano-ZnOs (5000 mg/kg) caused toxicity on development, and altered the zinc metabolism and biodistribution in mice. PMID:27732669

  20. Effects of Long-Term Exposure to Zinc Oxide Nanoparticles on Development, Zinc Metabolism and Biodistribution of Minerals (Zn, Fe, Cu, Mn) in Mice.

    PubMed

    Wang, Chao; Lu, Jianjun; Zhou, Le; Li, Jun; Xu, Jiaman; Li, Weijian; Zhang, Lili; Zhong, Xiang; Wang, Tian

    2016-01-01

    Zinc oxide nanoparticles (nano-ZnOs) are widely used and possess great potentials in agriculture and biomedicine. It is inevitable for human exposure to these nanoparticles. However, no study had been conducted to investigate the long term effects of nano-ZnOs. This study aimed at investigating effects of nano-ZnOs on development, zinc metabolism and biodistribution of minerals (Zn, Fe, Cu, and Mn) in mice from week 3 to 35. After the characteristics of nano-ZnOs were determined, they were added into the basal diet at 0, 50, 500 and 5000 mg/kg. Results indicated that added 50 and 500 mg/kg nano-ZnOs showed minimal toxicity. However, 5000 mg/kg nano-ZnOs significantly decreased body weight (from week 4 to 16) and increased the relative weights of the pancreas, brain and lung. Added 5000 mg/kg nano-ZnOs significantly increased the serum glutamic-pyruvic transaminase activity and zinc content, and significantly enhanced mRNA expression of zinc metabolism-related genes, including metallothionein 1(32.66 folds), metallothionein 2 (31.42 folds), ZIP8 (2.21folds), ZIP14 (2.45 folds), ZnT1 (4.76 folds), ZnT2 (6.19 folds) and ZnT4 (1.82 folds). The biodistribution determination showed that there was a significant accumulation of zinc in the liver, pancreas, kidney, and bones (tibia and fibula) after receiving 5000 mg/kg nano-ZnO diet, while no significant effects on Cu, Fe, and Mn levels, except for liver Fe content and pancreas Mn level. Our results demonstrated that long term exposure to 50 and 500 mg/kg nano-ZnO diets showed minimal toxicity. However, high dose of nano-ZnOs (5000 mg/kg) caused toxicity on development, and altered the zinc metabolism and biodistribution in mice.

  1. Personal exposures to airborne metals in London taxi drivers and office workers in 1995 and 1996.

    PubMed

    Pfeifer, G D; Harrison, R M; Lynam, D R

    1999-09-01

    In 1995, a petroleum marketer introduced a diesel fuel additive in the UK containing Mn as MMT (methylcyclopentadienyl manganese tricarbonyl). A small study of personal exposures to airborne Mn in London was conducted before and after introduction of the additive to identify any major impact of the additive on exposures. In 1995, personal exposures to Mn were measured in two groups, taxi drivers and office workers (10 subjects per group) for two consecutive 7-day periods. A similar study was carried out in 1996 to determine if exposures had changed. Samples were also analyzed for Ca, Al, Mg and Pb. In 1996, exposures to aerosol mass as total suspended particulates (TSP) and PM2.5 were measured in addition to the metals. Manganese exposures in this cohort did not increase as a result of introduction of the additive. However, a significant source of Mn exposure was discovered during the conduct of these tests. The mean exposure to Mn was higher among the office workers in both years than that of the taxi drivers. This was due to the fact that approximately half of the office workers commuted via the underground railway system where airborne dust and metal concentrations are significantly elevated over those in the general environment. Similar results have been noted in other cities having underground rail systems. Exposure to Mn, Pb, Ca, and Mg were not significantly different between the 2 years. Taxi drivers had higher exposures than office workers to Mg and Pb in both years. Commuting via the underground also had a significant impact on exposures to TSP, PM2.5, Al, and Ca, but had little effect on exposures to Mg. The aerosol in the underground was particularly enriched in Mn, approximately 10-fold, when compared to the aerosol in the general environment. There are several possible sources for this Mn, including mechanical wear of the steel wheels on the steel rais, vaporization of metal from sparking of the third rail, or brake wear.

  2. Effects of early exposure and lifetime exposure to intimate partner violence (IPV) on child adjustment.

    PubMed

    Graham-Bermann, Sandra A; Perkins, Suzanne

    2010-01-01

    Children exposed to overwhelming and potentially traumatic events early in their lives are considered at-risk for problems in adjustment. Yet it is not known whether it is the age of first exposure (AFE) to violence or the amount of violence that the child witnessed in their lifetime that has the greatest impact on adjustment. For a sample of 190 children ages 6 to 12 exposed to intimate partner violence, their mothers reported that the average length of their abusive relationship was 10 years. The majority of children were first exposed to family violence as infants (64%), with only 12% first exposed when school-aged. Both the AFE and an estimate of the cumulative amount of violence were significantly and negatively related to children's behavioral problems. However, in regression analyses controlling for child sex, ethnicity, age, and family environment variables, cumulative violence exposure accounted for greater variance in adjustment than did AFE. Furthermore, cumulative violence exposure mediated the relationship between AFE and externalizing behavior problems, indicating that the cumulative exposure to IPV outweighed the AFE in its effect on child adjustment.

  3. Early feeding affects resistance against cold exposure in young broiler chickens.

    PubMed

    van den Brand, H; Molenaar, R; van der Star, I; Meijerhof, R

    2010-04-01

    In field conditions, a fasting period of 24 to 72 h after hatch is common, which is associated with delayed gastrointestinal development and yolk utilization and retarded subsequent performance. Hardly any information is available about the influence of diet composition in the first days on later life and additionally, effects of early feeding on thermoregulatory development are also not known. The aim of this study was to investigate effects of diet composition in early fed broiler chickens on their (thermoregulatory) development. Shortly after hatch, 200 Hybro chickens (initial BW of 43.6 g) were assigned to 1 of 5 feed treatments: control, dextrose, albumen, prestarter, or prestarter plus fat. Water was available ad libitum. Measurements were done in 10 replicates of 4 chickens per treatment. At d 2 or 3, half of the chickens were exposed to 20 degrees C for 30 min to determine resistance against cold exposure and rectal temperature was determined just before, immediately after, and 30 min after the end of this cold exposure. Thereafter, all chickens were killed to investigate body development. Chickens in both prestarter groups developed faster than in the other 3 groups, expressed by a higher BW, yolk-free body mass, heart and liver weight, and higher chick and intestine length. Between d 2 and 3, differences in these variables among chickens from both prestarter groups and other groups increased. Rectal temperature before cold exposure was higher in chickens from both prestarter groups (40.6 and 40.7 degrees C, respectively) and decreased less (0.6 and 0.7 degrees C, respectively) during cold exposure than in chickens from the control (39.5 and 1.2 degrees C, respectively) and albumen group (39.8 and 2.1 degrees C, respectively), whereas chickens from the dextrose group were in between (40.4 and 1.2 degrees C, respectively). We conclude that early fed diet composition in broiler chickens is (besides general development) important for development of both body

  4. Early life permethrin exposure leads to hypervitaminosis D, nitric oxide and catecholamines impairment.

    PubMed

    Fedeli, Donatella; Carloni, Manuel; Nasuti, Cinzia; Gambini, Anna; Scocco, Vitangelo; Gabbianelli, Rosita

    2013-09-01

    The aim of this study is to gain more knowledge on the impact of early life pesticide exposure on premature aging. The effect of a low dose of the insecticide permethrin administered to rats during early life (1/50 LD50, from 6th to 21st day of life) was analyzed by measuring some metabolites in plasma and urine of 500-day-old animals. Significant differences in early life treated rats compared to the control group were found in the plasma levels of Ca(++), Na(+), 25-hydroxy-vitamin D, adrenaline, noradrenaline, nitric oxide, cholesterol and urea while in urine only Na(+) content was different. These results add information on the impact of permethrin during the neonatal period, supporting the evidence that early life environmental exposure to xenobiotics has long-term effects, inducing modifications in adulthood that can be revealed by the analysis of some macroelements, metabolites and catecholamines in plasma, when rats are 500 days old. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Early androgen exposure and human gender development.

    PubMed

    Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

    2015-01-01

    During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This

  6. Disproportionate Exposure to Early-Life Adversity and Sexual Orientation Disparities in Psychiatric Morbidity

    ERIC Educational Resources Information Center

    McLaughlin, Katie A.; Hatzenbuehler, Mark L.; Xuan, Ziming; Conron, Kerith J.

    2012-01-01

    Objectives: Lesbian, gay, and bisexual (LGB) populations exhibit elevated rates of psychiatric disorders compared to heterosexuals, and these disparities emerge early in the life course. We examined the role of exposure to early-life victimization and adversity--including physical and sexual abuse, homelessness, and intimate partner violence--in…

  7. Activation of a water molecule using a mononuclear Mn complex: from Mn-aquo, to Mn-hydroxo, to Mn-oxyl via charge compensation†

    PubMed Central

    Lassalle-Kaiser, Benedikt; Hureau, Christelle; Pantazis, Dimitrios A.; Pushkar, Yulia; Guillot, Régis; Yachandra, Vittal K.; Yano, Junko; Neese, Frank; Anxolabéhère-Mallart, Elodie

    2014-01-01

    Activation of a water molecule by the electrochemical oxidation of a Mn-aquo complex accompanied by the loss of protons is reported. The sequential (2 × 1 electron/1 proton) and direct (2 electron/2 proton) proton-coupled electrochemical oxidation of a non-porphyrinic six-coordinated Mn(II)OH2 complex into a mononuclear Mn(O) complex is described. The intermediate Mn(III)OH2 and Mn(III)OH complexes are electrochemically prepared and analysed. Complete deprotonation of the coordinated water molecule in the Mn(O) complex is confirmed by electrochemical data while the analysis of EXAFS data reveals a gradual shortening of an Mn–O bond upon oxidation from Mn(II)OH2 to Mn(III)OH and Mn(O). Reactivity experiments, DFT calculations and XANES pre-edge features provide strong evidence that the bonding in Mn(O) is best characterized by a Mn(III)-oxyl description. Such oxyl species could play a crucial role in natural and artificial water splitting reactions. We provide here a synthetic example for such species, obtained by electrochemical activation of a water ligand. PMID:24772190

  8. Early Childhood Lead Exposure and Academic Achievement: Evidence From Detroit Public Schools, 2008–2010

    PubMed Central

    Baker, Harolyn W.; Tufts, Margaret; Raymond, Randall E.; Salihu, Hamisu; Elliott, Michael R.

    2013-01-01

    Objectives. We assessed the long-term effect of early childhood lead exposure on academic achievement in mathematics, science, and reading among elementary and junior high school children. Methods. We linked early childhood blood lead testing surveillance data from the Detroit Department of Health and Wellness Promotion to educational testing data from the Detroit, Michigan, public schools. We used the linked data to investigate the effect of early childhood lead exposure on academic achievement among school-aged children, both marginally and adjusted for grade level, gender, race, language, maternal education, and socioeconomic status. Results. High blood lead levels before age 6 years were strongly associated with poor academic achievement in grades 3, 5, and 8. The odds of scoring less than proficient for those whose blood lead levels were greater than 10 micrograms per deciliter were more than twice the odds for those whose blood lead levels were less than 1 micrograms per deciliter after adjustment for potential confounders. Conclusions. Early childhood lead exposure was negatively associated with academic achievement in elementary and junior high school, after adjusting for key potential confounders. The control of lead poisoning should focus on primary prevention of lead exposure in children and development of special education programs for students with lead poisoning. PMID:23327265

  9. Early postnatal ozone exposure alters rat nodose and jugular sensory neuron development

    PubMed Central

    Zellner, Leor C.; Brundage, Kathleen M.; Hunter, Dawn D.; Dey, Richard D.

    2011-01-01

    Sensory neurons originating in nodose and jugular ganglia that innervate airway epithelium (airway neurons) play a role in inflammation observed following exposure to inhaled environmental irritants such as ozone (O3). Airway neurons can mediate airway inflammation through the release of the neuropeptide substance P (SP). While susceptibility to airway irritants is increased in early life, the developmental dynamics of afferent airway neurons are not well characterized. The hypothesis of this study was that airway neuron number might increase with increasing age, and that an acute, early postnatal O3 exposure might increase both the number of sensory airway neurons as well as the number SP-containing airway neurons. Studies using Fischer 344 rat pups were conducted to determine if age or acute O3 exposure might alter airway neuron number. Airway neurons in nodose and jugular ganglia were retrogradely labeled, removed, dissociated, and counted by means of a novel technique employing flow cytometry. In Study 1, neuron counts were conducted on postnatal days (PD) 6, 10, 15, 21, and 28. Numbers of total and airway neurons increased significantly between PD6 and PD10, then generally stabilized. In Study 2, animals were exposed to O3 (2 ppm) or filtered air (FA) on PD5 and neurons were counted on PD10, 15, 21, and 28. O3-exposed animals displayed significantly less total neurons on PD21 than FA controls. This study shows that age-related changes in neuron number occur, and that an acute, early postnatal O3 exposure significantly alters sensory neuron development. PMID:22140294

  10. Prenatal alcohol and other early childhood adverse exposures: Direct and indirect pathways to adolescent drinking

    PubMed Central

    Cornelius, Marie D.; De Genna, Natacha M.; Goldschmidt, Lidush; Larkby, Cynthia; Day, Nancy L.

    2016-01-01

    We examined direct and indirect pathways between adverse environmental exposures during gestation and childhood and drinking in mid-adolescence. Mothers and their offspring (n = 917 mother/child dyads) were followed prospectively from second trimester to a 16-year follow-up assessment. Interim assessments occurred at delivery, 6, 10, and 14 years. Adverse environmental factors included gestational exposures to alcohol, tobacco, and marijuana, exposures to childhood maltreatment and violence, maternal psychological symptoms, parenting practices, economic and home environments, and demographic characteristics of the mother and child. Indirect effects of early child behavioral characteristics including externalizing, internalizing activity, attention, and impulsivity were also examined. Polytomous logistic regression analyses were used to evaluate direct effects of adverse environmental exposures with level of adolescent drinking. Structural equation modeling (SEM) was applied to simultaneously estimate the relation between early adversity variables, childhood characteristics, and drinking level at age 16 while controlling for significant covariates. Level of drinking among the adolescent offspring was directly predicted by prenatal exposure to alcohol, less parental strictness, and exposures to maltreatment and violence during childhood. Whites and offspring with older mothers were more likely to drink at higher levels. There was a significant indirect effect between childhood exposure to violence and adolescent drinking via childhood externalizing behavior problems. All other hypothesized indirect pathways were not significant. Thus most of the early adversity measures directly predicted adolescent drinking and did not operate via childhood behavioral dysregulation characteristics. These results highlight the importance of adverse environmental exposures on pathways to adolescent drinking. PMID:26994529

  11. Generalized Anxiety and Major Depressive syndrome measured by the SCL-90-R in Two Manganese (Mn) Exposed Ohio Towns

    EPA Science Inventory

    Objective: Environmental exposure to manganese (Mn) may cause generalized anxiety (GA) and major depression (MD) in residents living in Mn-exposed areas. Marietta and East Liverpool are two Ohio towns identified as having elevated levels of Mn. The objective was to determine if l...

  12. State-of-the-science review: Does manganese exposure during welding pose a neurological risk?

    PubMed

    Santamaria, Annette B; Cushing, Colleen A; Antonini, James M; Finley, Brent L; Mowat, Fionna S

    2007-01-01

    Recent studies report that exposure to manganese (Mn), an essential component of welding electrodes and some steels, results in neurotoxicity and/or Parkinson's disease (PD) in welders. This "state-of-the-science" review presents a critical analysis of the published studies that were conducted on a variety of Mn-exposed occupational cohorts during the last 100 yr, as well as the regulatory history of Mn and welding fumes. Welders often perform a variety of different tasks with varying degrees of duration and ventilation, and hence, to accurately assess Mn exposures that occurred in occupational settings, some specific information on the historical work patterns of welders is desirable. This review includes a discussion of the types of exposures that occur during the welding process--for which limited information relating airborne Mn levels with specific welding activities exists--and the human health studies evaluating neurological effects in welders and other Mn-exposed cohorts, including miners, millers, and battery workers. Findings and implications of studies specifically conducted to evaluate neurobehavioral effects and the prevalence of PD in welders are also discussed. Existing exposure data indicate that, in general, Mn exposures in welders are less than those associated with the reports of clinical neurotoxicity (e.g., "manganism") in miners and smelter workers. It was also found that although manganism was observed in highly exposed workers, the scant exposure-response data available for welders do not support a conclusion that welding is associated with clinical neurotoxicity. The available data might support the development of reasonable "worst-case" exposure estimates for most welding activities, and suggest that exposure simulation studies would significantly refine such estimates. Our review ends with a discussion of the data gaps and areas for future research.

  13. Occupational exposure to manganese-containing welding fumes and pulmonary function indices among natural gas transmission pipeline welders.

    PubMed

    Hassani, Hamid; Golbabaei, Farideh; Ghahri, Asghar; Hosseini, Mostafa; Shirkhanloo, Hamid; Dinari, Behnam; Eskandari, Davood; Fallahi, Majid

    2012-01-01

    The objectives of this study were to evaluate manganese (Mn)-containing welding fumes' exposure, assess urinary Mn as a biomarker for Mn exposure and investigate the correlation of Mn in air, total fumes and urinary Mn with pulmonary function indices in 118 welders and 37 unexposed controls from two regions in Iran, Assaluyeh and Borujen. Air samples were collected on mixed cellulose ester membrane filters in personal air samplers and then analyzed using inductively coupled plasma atomic emission spectroscopy (ICP-AES) (NIOSH Method 7300). For all participants, urine samples were collected during the entire work shift, and Mn in urine was determined by graphite furnace atomic absorption spectroscopy according to NIOSH Method 8310. Spirometric measurements were also done for participants. The maximum exposures to airborne Mn and total fumes were 0.304 ± 0.256 mg/m(3) and 21.52 ± 9.40 mg/m(3), respectively. The urine Mn levels in the various groups ranged between 0.77 to 7.58 μg/l. The correlation between airborne Mn and urinary Mn was significant for total whole participants. Some values of spirometric indices were statistically lower in welders rather than controls. Our results indicate that many welders have been exposed to higher concentrations of Mn-containing welding fumes. Urinary Mn can be used as a biomarker for Mn exposure. There were weak inverse correlations between Mn-containing welding fumes and pulmonary function indices, and the inverse correlation between urinary Mn with forced vital capacities (FVC) and forced expiratory volume in 1 s (FEV1) was significant.

  14. Fe/Mn in olivine of carbonaceous meteorites

    NASA Technical Reports Server (NTRS)

    Steele, Ian M.

    1993-01-01

    Olivines in primitive meteorites show a range of Fe/Mn both within one grain and among grains suggesting that they have recorded changing conditions during or after growth. Because olivine should be an early forming phase, Fe/Mn is used here to infer these earliest conditions. Initial Fe/Mn in cores of isolated, euhedral forsterite in both C2 and C3 meteorites ranges from 25 to 35 but differs at grain edge. Murchison (C2) forsterites show Fe/Mn approaching 1.0 at the grain edge while Ornans Fe/Mn is near 60 at grain edge. These values are lower than the matrix Fe/Mn for both meteorites and the distinct difference in zoning profile indicates different processes operating during and after grain growth. The Fe/Mn of bulk samples from a particular source such as the Moon is nearly constant. Individual samples show variation suggesting that there is some fractionation of Mn from Fe. Minerals have their individual ranges of Fe/Mn which has been used to recognize different types of olivine within one meteorite. Extreme values of Fe/Mn below 1.0 occur in forsterite from some IDP's, UOC matrix, and C1 meteorites. There are apparently no detailed studies of Fe/Mn variation within single olivine grains. Forsterite grains in C2 and C3 carbonaceous chondrites show complex zoning, and the nearly pure forsterites (Fo greater than approximately 99.5) have high levels of some minor elements including Ti, Al, V, and Sc. There is disagreement on the original source of these grains and both chondrule and vapor growth have been proposed. In addition, there is clear evidence that diffusion has affected the outer margins but in some cases the whole grain. Within the cores, the FeO range is limited, and if growing under constant conditions, the Fe/Mn should be near constant as there is little fractionation of Mn from Fe by forsterite. Additionally, there are apparently no co-crystallizing phases as evidenced by a lack of common inclusions in the forsterites. These observations are now

  15. Long-term effect of early-life stress from earthquake exposure on working memory in adulthood.

    PubMed

    Li, Na; Wang, Yumei; Zhao, Xiaochuan; Gao, Yuanyuan; Song, Mei; Yu, Lulu; Wang, Lan; Li, Ning; Chen, Qianqian; Li, Yunpeng; Cai, Jiajia; Wang, Xueyi

    2015-01-01

    The present study aimed to investigate the long-term effect of 1976 Tangshan earthquake exposure in early life on performance of working memory in adulthood. A total of 907 study subjects born and raised in Tangshan were enrolled in this study. They were divided into three groups according to the dates of birth: infant exposure (3-12 months, n=274), prenatal exposure (n=269), and no exposure (born at least 1 year after the earthquake, n=364). The prenatal group was further divided into first, second, and third trimester subgroups based on the timing of exposure during pregnancy. Hopkins Verbal Learning Test-Revised and Brief Visuospatial Memory Test-Revised (BVMT-R) were used to measure the performance of working memory. Unconditional logistic regression analysis was used to analyze the influential factors for impaired working memory. The Hopkins Verbal Learning Test-Revised scores did not show significant difference across the three groups. Compared with no exposure group, the BVMT-R scores were slightly lower in the prenatal exposure group and markedly decreased in the infant exposure group. When the BVMT-R scores were analyzed in three subgroups, the results showed that the subjects whose mothers were exposed to earthquake in the second and third trimesters of pregnancy had significantly lower BVMT-R scores compared with those in the first trimester. Education level and early-life earthquake exposure were identified as independent risk factors for reduced performance of visuospatial memory indicated by lower BVMT-R scores. Infant exposure to earthquake-related stress impairs visuospatial memory in adulthood. Fetuses in the middle and late stages of development are more vulnerable to stress-induced damage that consequently results in impaired visuospatial memory. Education and early-life trauma can also influence the performance of working memory in adulthood.

  16. Occupational Exposure to Manganese and Fine Motor Skills in Elderly Men: Results from the Heinz Nixdorf Recall Study.

    PubMed

    Pesch, Beate; Casjens, Swaantje; Weiss, Tobias; Kendzia, Benjamin; Arendt, Marina; Eisele, Lewin; Behrens, Thomas; Ulrich, Nadin; Pundt, Noreen; Marr, Anja; Robens, Sibylle; Van Thriel, Christoph; Van Gelder, Rainer; Aschner, Michael; Moebus, Susanne; Dragano, Nico; Brüning, Thomas; Jöckel, Karl-Heinz

    2017-11-10

    Exposure to manganese (Mn) may cause movement disorders, but less is known whether the effects persist after the termination of exposure. This study investigated the association between former exposure to Mn and fine motor deficits in elderly men from an industrial area with steel production. Data on the occupational history and fine motor tests were obtained from the second follow-up of the prospective Heinz Nixdorf Recall Study (2011-2014). The study population included 1232 men (median age 68 years). Mn in blood (MnB) was determined in archived samples (2000-2003). The association between Mn exposure (working as welder or in other at-risk occupations, cumulative exposure to inhalable Mn, MnB) with various motor functions (errors in line tracing, steadiness, or aiming and tapping hits) was investigated with Poisson and logistic regression, adjusted for iron status and other covariates. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for substantially impaired dexterity (errors >90th percentile, tapping hits <10th percentile). The median of cumulative exposure to inhalable Mn was 58 µg m-3 years in 322 men who ever worked in at-risk occupations. Although we observed a partly better motor performance of exposed workers at group level, we found fewer tapping hits in men with cumulative Mn exposure >184.8 µg m-3 years (OR 2.15, 95% CI 1.17-3.94). MnB ≥ 15 µg l-1, serum ferritin ≥ 400 µg l-1, and gamma-glutamyl transferase ≥74 U l-1 were associated with a greater number of errors in line tracing. We found evidence that exposure to inhalable Mn may carry a risk for dexterity deficits. Whether these deficits can be exclusively attributed to Mn remains to be elucidated, as airborne Mn is strongly correlated with iron in metal fumes, and high ferritin was also associated with errors in line tracing. Furthermore, hand training effects must be taken into account when testing for fine motor skills. © The Author 2017. Published by Oxford

  17. Effects of pulmonary exposure to chemically-distinct welding fumes on neuroendocrine markers of toxicity.

    PubMed

    Krajnak, K; Sriram, K; Johnson, C; Roberts, J R; Mercer, R; Miller, G R; Wirth, O; Antonini, J M

    2017-01-01

    Exposure to welding fumes may result in disorders of the pulmonary, cardiovascular, and reproductive systems. Welders are also at a greater risk of developing symptoms similar to those seen in individuals with idiopathic Parkinson's disease. In welders, there are studies that suggest that alterations in circulating prolactin concentrations may be indicative of injury to the dopamine (DA) neurons in the substantia nigra. The goal of these studies was to use an established model of welding particulate exposure to mimic the effects of welding fume inhalation on reproductive functions. Since previous investigators suggested that changes in circulating prolactin may be an early marker of DA neuron injury, movement disorders, and reproductive dysfunction, prolactin, hypothalamic tyrosine hydroxylase (TH) levels (a marker of DA synthesis), and other measures of hypothalamic-pituitary-gonadal (HPG) function were measured after repetitive instillation of welding fume particulates generated by flux core arc-hard surfacing (FCA-HS), manual metal arc-hard surfacing (MMA-HS) or gas metal arc-mild steel (GMA-MS) welding, or manganese chloride (MnCl 2 ). Exposure to welding fume particulate resulted in the accumulation of various metals in the pituitary and testes of rats, along with changes in hypothalamic TH and serum prolactin levels. Exposure to particulates with high concentrations of soluble manganese (Mn) appeared to exert the greatest influence on TH activity levels and serum prolactin concentrations. Thus, circulating prolactin levels may serve as a biomarker for welding fume/Mn-induced neurotoxicity. Other reproductive measures were collected, and these data were consistent with epidemiological findings that prolactin and testosterone may serve as biomarkers of welding particulate induced DA neuron and reproductive dysfunction.

  18. Minimal second language exposure, SES, and early word comprehension: New evidence from a direct assessment*

    PubMed Central

    Deanda, Stephanie; Arias-Trejo, Natalia; Poulin-Dubois, Diane; Zesiger, Pascal; Friend, Margaret

    2015-01-01

    Although the extant literature provides robust evidence of the influence of language exposure and socioeconomic status (SES) on language acquisition, it is unknown how sensitive the early receptive vocabulary system is to these factors. The current study investigates effects of minimal second language exposure and SES on the comprehension vocabulary of 16-month-old children in the language in which they receive the greatest exposure. Study 1 revealed minimal second language exposure and SES exert significant and independent effects on a direct measure of vocabulary comprehension in English-dominant and English monolingual children (N = 72). In Study 2, we replicated the effect of minimal second language exposure in Spanish-dominant and Spanish monolingual children (N = 86), however no effect of SES on vocabulary was obtained. Our results emphasize the sensitivity of the language system to minimal changes in the environment in early development. PMID:26957947

  19. Community Exposure to Air Manganese and Motor and Cognitive Outcomes

    EPA Science Inventory

    Although manganese (Mn) is an essential nutrient, occupational studies have shown inhaling high levels of Mn can lead to adverse nervous system health effects. Few studies have examined the health effects of air-Mn exposure on adults in a community. We conducted a cross-sectional...

  20. Infant self-regulation and early childhood media exposure.

    PubMed

    Radesky, Jenny S; Silverstein, Michael; Zuckerman, Barry; Christakis, Dimitri A

    2014-05-01

    Examine prospective associations between parent-reported early childhood self-regulation problems and media exposure (television and video viewing) at 2 years. We hypothesized that children with poor self-regulation would consume more media, possibly as a parent coping strategy. We used data from 7450 children in the Early Childhood Longitudinal Study-Birth Cohort. When children were 9 months and 2 years old, parents completed the Infant Toddler Symptom Checklist (ITSC), a validated scale of self-regulation. With daily media use at 2 years as our outcome, we conducted weighted multivariable regression analyses, controlling for child, maternal, and household characteristics. Children watched an average of 2.3 hours per day (SD 1.9) of media at age 2 years. Infants with poor self-regulation (9-month ITSC score ≥3) viewed 0.23 hour per day (95% confidence interval [CI] 0.12-0.35) more media at 2 years compared with those with 9-month ITSC score of 0 to 2; this remained significant in adjusted models (0.15 hour per day [95% CI 0.02-0.28]). Children rated as having persistent self-regulation problems (ITSC ≥3 at both 9 months and 2 years) were even more likely to consume media at age 2 (adjusted β 0.21 hour per day [95% CI 0.03-0.39]; adjusted odds ratio for >2 hours per day 1.40 [95% CI 1.14-1.71]). These associations were slightly stronger in low socioeconomic status and English-speaking households. Early childhood self-regulation problems are associated with mildly increased media exposure, even after controlling for important confounding variables. Understanding this relationship may provide insight into helping parents reduce their children's screen time. Copyright © 2014 by the American Academy of Pediatrics.

  1. Structure and magnetism of a Mn(III)-Mn(II)-Mn(II)-Mn(III) chain complex.

    PubMed

    Uhrecký, Róbert; Moncoľ, Ján; Koman, Marian; Titiš, Ján; Boča, Roman

    2013-07-14

    A novel tetranuclear manganese(II/III) complex with anions of pyridine-2,6-dicarboxylic acid (dipicolinic acid) has been synthesised and magneto-structurally characterised. The crystal structure of [Mn(II)2Mn(III)2(dipic)6(H2O)4]·2CH3OH·4H2O has been determined by single-crystal X-ray diffraction. The tetranuclear complex molecule [Mn(II)2Mn(III)2(dipic)6(H2O)4] is centrosymmetric and two manganese(II) and two manganese(III) atoms are bridged by four dipicolinate ligands. The complex molecules and uncoordinated water and methanol molecules are connected through hydrogen bonds and they form a 3D supramolecular hydrogen-bonding network.

  2. The effect of a low iron diet and early life methylmercury exposure in Daphnia pulex

    PubMed Central

    Hudson, Sherri L.; Doke, Dzigbodi A.; Gohlke, Julia M.

    2016-01-01

    Iron (Fe) deficiency increases risk for adverse health outcomes in humans; however little is known about the potential interaction with methylmercury (MeHg) exposure. Studies testing multiple stressor hypotheses are expensive and time consuming in mammalian model systems; therefore, determining relevance of alternative models is important. Daphnia pulex were fed standard or low-Fe diets of freshwater algae, Ankistrodesmus falcatus. MeHgCl (1600 ng/L) or vehicle was added to culture media for 24 h during early life, and the combinatorial effects of a low-Fe diet and MeHg exposure on lifespan, maturation time, and reproduction were evaluated. Lipid storage effects were measured using image analysis of Oil Red O staining and triacylglyceride quantification. Our results show a dose-dependent reduction in lifespan in D. pulex fed low Fe diets. Lipid analysis suggests an interactive effect of diet and MeHg exposure, with MeHg exposure increasing lipid storage in D. pulex fed a low-Fe diet. These findings suggest the effects of dietary iron intake and early life MeHg exposure in D. pulex may be mediated by changes in energetics that result in differential lipid storage. Therefore, lipid storage in D. pulex may be a useful screen for detecting long-term effects of multiple stressors early in life. PMID:26806633

  3. Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function.

    PubMed

    Fleisch, Abby F; Rifas-Shiman, Sheryl L; Mora, Ana M; Calafat, Antonia M; Ye, Xiaoyun; Luttmann-Gibson, Heike; Gillman, Matthew W; Oken, Emily; Sagiv, Sharon K

    2017-03-01

    Perfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited. We studied 665 mother-child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999-2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex. Children with higher PFAS concentrations had lower HOMA-IR [e.g., -10.1% (95% CI: -17.3, -2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: -15.6% (95% CI: -25.4, -4.6) vs. -6.1% (95% CI: -16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring. We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481-487; http://dx.doi.org/10.1289/EHP303.

  4. Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function

    PubMed Central

    Fleisch, Abby F.; Rifas-Shiman, Sheryl L.; Mora, Ana M.; Calafat, Antonia M.; Ye, Xiaoyun; Luttmann-Gibson, Heike; Gillman, Matthew W.; Oken, Emily; Sagiv, Sharon K.

    2016-01-01

    Background: Perfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited. Methods: We studied 665 mother–child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999–2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex. Results: Children with higher PFAS concentrations had lower HOMA-IR [e.g., –10.1% (95% CI: –17.3, –2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: –15.6% (95% CI: –25.4, –4.6) vs. –6.1% (95% CI: –16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring. Conclusions: We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481–487; http://dx.doi.org/10.1289/EHP303 PMID:27586368

  5. ENVIRONMENTAL MANGANESE: GUIDELINE EXPOSURE LEVELS, EVIDENCE OF HEALTH EFFECTS AND RESEARCH NEEDS.

    EPA Science Inventory

    Introduction. The ubiquitous element, manganese (Mn), is an essential nutrient, but toxic at excessive exposure levels. The US EPA, therefore, set guideline levels for Mn exposure through inhalation (reference concentration-RfC=0.05 g/m3) and ingestion (reference dose-RfD=0.14 m...

  6. Early life exposure to China's 1959-61 famine and midlife cognition.

    PubMed

    Xu, Hongwei; Zhang, Zhenmei; Li, Lydia; Liu, Jinyu

    2018-02-01

    Existing studies of the 1944-45 Dutch famine found little evidence of the association between early life malnutrition and midlife cognition. Among 2446 rural participants born between 1958 and 1963 in the China Health and Retirement Longitudinal Study, we examined effects of exposure to China's 1959-61 Great Leap Forward famine during prenatal and early postnatal life, on four cognitive measures in 2011 (baseline) and changes in cognition between 2011 and 2013 (first follow-up). We obtained difference-in-differences (DID) estimates of the famine effects by exploiting temporal variation in the timing and duration of famine exposure across six birth cohorts born between 1958 and 1963, together with geographical variation in famine severity at the prefecture level. After adjusting for gender, marital status and provincial fixed effects, we found that the 1961 cohort who experienced full-term prenatal and partial-term postnatal exposures to famine had lower scores on the Telephone Interview of Cognitive Status (TICS), a test of drawing pentagons, and general cognition at age 50 years compared with the unexposed 1963 cohort. Adjusting for education, the famine effects on drawing pentagons and general cognition were fully attenuated, but the effect on TICS persisted. We also found a robust negative famine effect on the longitudinal change in general cognition during the 2-year follow-up in the 1959 cohort. Severe nutritional deprivation during prenatal and postnatal periods has a lasting impact on cognitive performance in Chinese adults in their early 50s. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

  7. Early Childhood Risk Factors for Mealtime TV Exposure and Engagement in Low-Income Families.

    PubMed

    Domoff, Sarah E; Lumeng, Julie C; Kaciroti, Niko; Miller, Alison L

    To identify whether child and mother characteristics in early childhood predict TV exposure and engagement during mealtime in middle childhood. A total of 220 low-income mother-child dyads participated. Children were 4.26 years old (SD = 0.51) at baseline and 5.94 years (SD = 0.68) at 2-year follow-up. Mothers completed baseline measures of child negative emotionality and parenting practices. Family mealtimes were video recorded and coded for background TV exposure and child TV engagement. Multinomial logistic regression tested whether child emotionality and parenting practices during early childhood predicted risk of child TV exposure or engagement during mealtime, relative to no TV use, 2 years later. Children with greater negative emotionality in early childhood were more likely to engage with TV during mealtime than to have no TV. Similarly, early parenting disciplinary practices characterized by over-reactivity and laxness increased the risk for child TV engagement versus no TV during mealtime approximately 2 years later. We identified 2 factors that associated with an increased risk for TV viewing during meals. Helping parents manage child negative emotionality using positive parenting strategies might reduce later child TV engagement and improve the quality of family mealtimes. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  8. Early Childhood Risk Factors for Mealtime TV Exposure and Engagement in Low-Income Families

    PubMed Central

    Domoff, Sarah E.; Lumeng, Julie C.; Kaciroti, Niko; Miller, Alison L.

    2016-01-01

    OBJECTIVE To identify whether child and mother characteristics in early childhood predict TV exposure and engagement during mealtime in middle childhood. METHODS A total of 220 low-income mother-child dyads participated. Children were 4.26 years old (SD = 0.51) at baseline and 5.94 years (SD = 0.68) at two-year follow-up. Mothers completed baseline measures of child negative emotionality and parenting practices. Family mealtimes were video-recorded and coded for background TV exposure and child TV engagement. Multinomial logistic regression tested whether child emotionality and parenting practices during early childhood predicted risk of child TV exposure or engagement during mealtime, relative to no TV use, two years later. RESULTS Children with greater negative emotionality in early childhood were more likely to engage with TV during mealtime than to have no TV. Similarly, early parenting disciplinary practices characterized by over-reactivity and laxness increased the risk for child TV engagement versus no TV during mealtime approximately two years later. CONCLUSIONS We identified two factors that associated with an increased risk for TV viewing during meals. Helping parents manage child negative emotionality using positive parenting strategies may reduce later child TV engagement and improve the quality of family mealtimes. PMID:27979749

  9. Fetal exposure to lead during pregnancy and the risk of preterm and early-term deliveries.

    PubMed

    Cheng, Lu; Zhang, Bin; Huo, Wenqian; Cao, Zhongqiang; Liu, Wenyu; Liao, Jiaqiang; Xia, Wei; Xu, Shunqing; Li, Yuanyuan

    2017-08-01

    Studies have reported the association between lead exposure during pregnancy and preterm birth. However, findings are still inconsistent. This prospective birth cohort study evaluated the risks of preterm and early-term births and its association with prenatal lead exposure in Hubei, China. A total of 7299 pregnant women were selected from the Healthy Baby Cohort. Maternal urinary lead levels were measured by the Inductively Coupled Plasma Mass Spectrometry. The associations between tertiles of urinary lead levels and the risks of preterm and early-term deliveries were assessed using multiple logistic regression models. The geometric mean of creatinine-adjusted urinary lead concentrations among all participating mothers, preterm birth, and early-term birth were 3.19, 3.68, and 3.17μg/g creatinine, respectively. A significant increase in the risk of preterm births was associated with the highest urinary lead tertile after adjusting for confounders with odds ratio (OR) of 1.96. The association was more pronounced among 25-36 years old mothers with OR of 2.03. Though significant p trends were observed between lead exposure (medium and high tertiles) and the risk of early-term births, their ORs were not significant. Our findings indicate that the risk of preterm birth might increase with higher fetal lead exposure, particularly among women between the age of 25 and 36 years. Copyright © 2017 Elsevier GmbH. All rights reserved.

  10. Pathways of inhalation exposure to manganese in children living near a ferromanganese refinery: A structural equation modeling approach

    EPA Science Inventory

    Manganese (Mn) is both essential element and neurotoxicant. Exposure to Mn can occur from various sources and routes. Structural equation modeling was used to examine routes of exposure to Mn among children residing near a ferromanganese refinery in Marietta, Ohio. An inhalation ...

  11. Precipitation of Carbides in Early Aging Stages and Their Crystallographic Orientations in Hadfield Steel Mn13

    NASA Astrophysics Data System (ADS)

    Ding, Zhimin; Liang, Bo; Zhao, Ruirong; Chen, Chunhuan

    2015-05-01

    The methods of transmission electron microscopy (TEM) and electron diffraction are used to study the carbides precipitated in Hadfield steel Mn13 during 2-h aging at 475°C. It is shown that carbides of types (Fe, Mn, Cr)23C6 and mixed (Fe, Mn, Cr)7C3 + (Fe, Mn, Cr)3C precipitate simultaneously over austenite grain boundaries. The data on precipitation of M23C- and M7C3-type carbides in a Hadfield steel after water quenching and aging are pioneer ones. Strict orientation relations of the M23C6 carbides and of the austenite matrix are determined.

  12. Risk Factors in Early Child Development: Is Prenatal Cocaine/Polydrug Exposure a Key Variable?

    ERIC Educational Resources Information Center

    Phelps, Leadelle; Wallace, Nancy Virginia; Bontrager, Annie

    1997-01-01

    Assessed the effect of cocaine/polydrug in utero exposure on early childhood development while controlling for covariant factors. Analysis of two matched samples of preschoolers (20 with drug exposure and 20 without) revealed that both groups scored approximately one standard deviation below the expected mean in social skills, auditory…

  13. Exposure to Environmental Air Manganese and Medication Use

    EPA Science Inventory

    Manganese (Mn) is an essential element with natural low levels found in water, food, and air, but due to industrialized processes, both workplace and the environmental exposures to Mn have increased. Recently, environmental studies have reported physical and mental health problem...

  14. Exposure to bitumen fumes and genotoxic effects on Turkish asphalt workers.

    PubMed

    Karaman, Ali; Pirim, Ibrahim

    2009-04-01

    Bitumen fumes consist essentially of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, some of which are known to be carcinogenic or cocarcinogenic in humans. The aim of this study was to investigate exposure to asphalt fumes among Turkish asphalt workers and determine whether any effects could be detected with genotoxic tests. The study included 26 asphalt workers and 24 control subjects. Sister chromatid exchange (SCE) and micronucleus (MN) were determined in peripheral lymphocytes. Urinary 1-hydroxypyrene (1-OHP) excretion was used as a biomarker of occupational exposure to PAHs. The asphalt workers had a significant increase in SCEs and MN (for each, p < 0.001). A positive correlation existed between the duration of exposure and rates of SCE or MN frequencies (r = 0.49, p < 0.05; r = 0.53, p < 0.05, respectively). The concentration of 1-OHP in urine was higher for the asphalt workers than for the controls (p < 0.001). However, we found that there was no statistically significant correlation between the urinary 1-OHP concentration and SCEs or MN frequencies (r = 0.25, p > 0.5; r = 0.17, p > 0.5, respectively). This study shows that Turkish asphalt workers have an increased exposure to PAHs from bitumen fumes, and genotoxic effects could be detected by SCEs and MN tests.

  15. Early Visual Language Exposure and Emergent Literacy in Preschool Deaf Children: Findings from a National Longitudinal Study

    ERIC Educational Resources Information Center

    Allen, Thomas E.; Letteri, Amy; Choi, Song Hoa; Dang, Daqian

    2014-01-01

    A brief review is provided of recent research on the impact of early visual language exposure on a variety of developmental outcomes, including literacy, cognition, and social adjustment. This body of work points to the great importance of giving young deaf children early exposure to a visual language as a critical precursor to the acquisition of…

  16. Multicopper Oxidase Involvement in Both Mn(II) and Mn(III) Oxidation during Bacterial Formation of MnO2

    PubMed Central

    Soldatova, Alexandra V.; Butterfield, Cristina; Oyerinde, Oyeyemi F.; Tebo, Bradley M.; Spiro, Thomas G.

    2013-01-01

    Global cycling of environmental manganese requires catalysis by bacteria and fungi for MnO2 formation, since abiotic Mn(II) oxidation is slow under ambient conditions. Genetic evidence from several bacteria implicates multicopper oxidases (MCOs) as being required for MnO2 formation. However, MCOs catalyze one-electron oxidations, whereas conversion of Mn(II) to MnO2 is a two-electron process. Trapping experiments with pyrophosphate (PP), a Mn(III) chelator, have demonstrated that Mn(III) is an intermediate in Mn(II) oxidation when mediated by exosporium from the Mn-oxidizing bacterium Bacillus SG-1. The reaction of Mn(II) depends on O2 and is inhibited by azide, consistent with MCO catalysis. We show that the subsequent conversion of Mn(III) to MnO2 also depends on O2 and is inhibited by azide. Thus, both oxidation steps appear to be MCO-mediated, likely by the same enzyme, indicated by genetic evidence to be the MnxG gene product. We propose a model of how the manganese oxidase active site may be organized to couple successive electron transfers to the formation of polynuclear Mn(IV) complexes as precursors to MnO2 formation. PMID:22892957

  17. Manganese (Mn) Oxidation Increases Intracellular Mn in Pseudomonas putida GB-1

    PubMed Central

    Banh, Andy; Chavez, Valarie; Doi, Julia; Nguyen, Allison; Hernandez, Sophia; Ha, Vu; Jimenez, Peter; Espinoza, Fernanda; Johnson, Hope A.

    2013-01-01

    Bacterial manganese (Mn) oxidation plays an important role in the global biogeochemical cycling of Mn and other compounds, and the diversity and prevalence of Mn oxidizers have been well established. Despite many hypotheses of why these bacteria may oxidize Mn, the physiological reasons remain elusive. Intracellular Mn levels were determined for Pseudomonas putida GB-1 grown in the presence or absence of Mn by inductively coupled plasma mass spectrometry (ICP-MS). Mn oxidizing wild type P. putida GB-1 had higher intracellular Mn than non Mn oxidizing mutants grown under the same conditions. P. putida GB-1 had a 5 fold increase in intracellular Mn compared to the non Mn oxidizing mutant P. putida GB-1-007 and a 59 fold increase in intracellular Mn compared to P. putida GB-1 ∆2665 ∆2447. The intracellular Mn is primarily associated with the less than 3 kDa fraction, suggesting it is not bound to protein. Protein oxidation levels in Mn oxidizing and non oxidizing cultures were relatively similar, yet Mn oxidation did increase survival of P. putida GB-1 when oxidatively stressed. This study is the first to link Mn oxidation to Mn homeostasis and oxidative stress protection. PMID:24147089

  18. The effect of exposure to hypergravity on pregnant rat dams, pregnancy outcome and early neonatal development

    NASA Astrophysics Data System (ADS)

    Ladd, B.; Nguon, K.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that hypergravity exposure affects food intake and mass gain during pregnancy. In the present study, we explored the hypothesis that changes in maternal body mass in hypergravity-exposed pregnant rat dams affect pregnancy outcome and early offspring development. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravity and by exposure during critical developmental periods. To test this hypothesis, we compared maternal body mass gain, food consumption, birth outcome and early offspring development between Sprague Dawley rat dams exposed to graded (1.5 1.75G) chronic hypergravity (HG) or rotation (rotational control, RC) on a 24-ft centrifuge for 22.5 h starting on gestational day (G) 10 with dams housed under identical conditions but not exposed to hypergravity (SC). We also compared maternal body mass, food consumption, birth outcome and early offspring development between rat dams exposed to 1.65G during different stages of pregnancy and nursing. Exposure to hypergravity resulted in transient loss in body mass and prolonged decrease in food consumption in HG dams, but the changes observed at 1.5G were not magnified at 1.65G or 1.75G. On the other hand RC dams gained more mass and consumed more food than SC dams. Exposure to hypergravity also affected pregnancy outcome as evidenced by decreased litter size, lowered neonatal mass at birth, and higher neonatal mortality; pregnancy outcome was not affected in RC dams. Neonatal changes evidenced by impaired righting response observed at 1.5G was magnified at higher gravity and was dependent on the period of hypergravity exposure. On the other hand, righting response was improved in RC neonates. Hypergravity exposure during early postpartum affected the food consumption of nursing mothers and affected early survival of their offspring. The changes observed in dams and neonates appear to be due to hypergravity exposure since animals exposed to the rotation

  19. Associations between content types of early media exposure and subsequent attentional problems.

    PubMed

    Zimmerman, Frederick J; Christakis, Dimitri A

    2007-11-01

    Television and video/DVD viewing among very young children has become both pervasive and heavy. Previous studies have reported an association between early media exposure and problems with attention regulation but did not have data on the content type that children watched. We tested the hypothesis that early television viewing of 3 content types is associated with subsequent attentional problems. The 3 different content types are educational, nonviolent entertainment, and violent entertainment. Participants were children in a nationally representative sample collected in 1997 and reassessed in 2002. The analysis was a logistic regression of a high score on a validated parent-reported measure of attentional problems, regressed on early television exposure by content and several important sociodemographic control variables. Viewing of educational television before age 3 was not associated with attentional problems 5 years later. However, viewing of either violent or non-violent entertainment television before age 3 was significantly associated with subsequent attentional problems, and the magnitude of the association was large. Viewing of any content type at ages 4 to 5 was not associated with subsequent problems. The association between early television viewing and subsequent attentional problems is specific to noneducational viewing and to viewing before age 3.

  20. Neighborhood Violent Crime and Academic Growth in Chicago: Lasting Effects of Early Exposure*

    PubMed Central

    Burdick-Will, Julia

    2017-01-01

    A large body of research documents the importance of early experiences for later academic, social, and economic success. Exposure to an unsafe neighborhood is no exception. Living in a violent neighborhood can influence the stress levels, protective behaviors, and community interactions of both parents and children in ways that generate cumulative educational disadvantage. Using nine years (2002–2011) of detailed crime data from the Chicago Police Department and longitudinal administrative data from the Chicago Public Schools, I estimate the influence of early exposure to neighborhood violence on growth in standardized test scores over time. Student fixed-effects are included to remove any bias due to constant differences between students. The results show that children from more violent neighborhoods fall farther behind their peers from safer neighborhoods as they progress through school. These effects are comparable in size to the independent association with socioeconomic disadvantage and an annual measure of more recent neighborhood violence exposure. PMID:29129943

  1. Environmental Exposure to Manganese in Air: Associations ...

    EPA Pesticide Factsheets

    Manganese (Mn), an essential element, can be neurotoxic in high doses. This cross-sectional study explored the oognitive function of adults residing in two towns (Marietta and East Liverpool, Ohio, USA) identified as having high levels of environmental airborne Mn from industrial sources. Air-Mn site surface emissions method modeling for total suspended particulate (TSP) ranged from 0.03 to 1.61 µg/m(3) in Marietta and 0.01-6.32 µg/m(3) in East Liverpool. A comprehensive screening test battery of cognitive function, including the domains of abstract thinking, attention/concentration, executive function and memory was administered. The mean age of the participants was 56 years (±10.8 years). Participants were mostly female (59.1) and primarily white (94.6%). Significant relationships (p<0.05) were found between Mn exposure and performance on working and visuospatial memory (e.g., Rey-0 Immediate B3=0.19, Rey-0 Delayed B3=0.16) and verbal skills (e.g., Similarities B3=0.19). Using extensive cognitive testing and computer modeling of 10-plus years of measured air monitoring data, this study suggests that long-term environmental exposure to high levels of air-Mn, the exposure metric of this paper, may result in mild deficits of cognitive function in adult populations. This study addresses research questions under Sustainable and Healthy Communities (2.2.1.6 lessons learned, best practices and stakeholder feedback from community and tribal participa

  2. Kinetic Investigations of SiMn Slags From Different Mn Sources

    NASA Astrophysics Data System (ADS)

    Kim, Pyunghwa Peace; Tangstad, Merete

    2018-06-01

    The kinetics of MnO and SiO2 reduction were investigated for Silicomanganese (SiMn) slags using a Thermogravimetric analysis (TGA) between 1773 K and 1923 K (1500 °C and 1650 °C) under CO atmospheric pressure. The charge materials were based on Assmang ore and HC FeMn Slag. Rate models for MnO and SiO2 reduction were applied to describe the metal-producing rates, as shown by the following equations: r_{MnO} = k_{MnO} × A × ( {a_{MnO} - {a_{Mn} }/{K_{T }}} ) r_{{{SiO}2 }} = k_{SiO2} × A × ( {a_{{{SiO}2 }} - {a_{Si} }/{K_{T }}} ). The results show that the choice of raw materials in the charge considerably affected the reduction rate of MnO and SiO2. The highest reduction rate was found to be from charges using HC FeMn slag. The difference in the driving forces was insignificant among the SiMn slags, and the similar slag viscosities could not explain the different reduction rates. Instead, the difference is attributed to small amounts of sulfur and the amount of iron in the charge. In addition, the rate models were applicable to describe the reduction of MnO and SiO2 in SiMn slags.

  3. Assessment of saliva, hair and toenails as biomarkers of low level exposure to manganese from drinking water in children.

    PubMed

    Ntihabose, Ruth; Surette, Céline; Foucher, Delphine; Clarisse, Olivier; Bouchard, Maryse F

    2018-01-01

    We evaluated hair, toenails, and saliva (whole and supernatant) as biomarkers of exposure to manganese (Mn) in 274 school age children (6-13 years) consuming well water in southeastern New Brunswick, Canada. Mn concentrations in tap water ranged from <0.03 to 1046μgL -1 (geometric mean 5.96μgL -1 ). The geometric mean of Mn intake resulting from the consumption of water was 0.25 (0-34.95) μg kg -1 day -1 . Both Mn concentration in water and Mn intake were significantly correlated with Mn in hair (r=0.60 and r=0.53, respectively), Mn in toenail (r=0.29 and r=0.37 respectively) and to a lesser extent with Mn in saliva supernatant (r=0.14 and r=0.18, respectively). Mn in whole saliva did not correlate with Mn in water or Mn intake. Both Mn in hair and Mn in toenail allowed to discriminate the most exposed group from the least exposed group, based on Mn in water and Mn intake from water. In this group of children with low level Mn exposure, Mn concentrations in hair, and toenails reflected reasonably well Mn exposure from drinking water, whereas Mn content in saliva correlated less strongly. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood.

    PubMed

    Parker, Matthew O; Evans, Alexandra M-D; Brock, Alistair J; Combe, Fraser J; Teh, Muy-Teck; Brennan, Caroline H

    2016-01-01

    Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning. © 2014 Society for the Study of Addiction.

  5. Ethanol exposure during the early first trimester equivalent impairs reflexive motor activity and heightens fearfulness in an avian model.

    PubMed

    Smith, Susan M; Flentke, George R; Kragtorp, Katherine A; Tessmer, Laura

    2011-02-01

    Prenatal alcohol exposure is a leading cause of childhood neurodevelopmental disability. The adverse behavioral effects of alcohol exposure during the second and third trimester are well documented; less clear is whether early first trimester-equivalent exposures also alter behavior. We investigated this question using an established chick model of alcohol exposure. In ovo embryos experienced a single, acute ethanol exposure that spanned gastrulation through neuroectoderm induction and early brain patterning (19-22h incubation). At 7 days posthatch, the chicks were evaluated for reflexive motor function (wingflap extension, righting reflex), fearfulness (tonic immobility [TI]), and fear/social reinstatement (open-field behavior). Chicks exposed to a peak ethanol level of 0.23-0.28% were compared against untreated and saline-treated controls. Birds receiving early ethanol exposure had a normal righting reflex and a significantly reduced wingflap extension in response to a sudden descent. The ethanol-treated chicks also displayed heightened fearfulness, reflected in increased frequency of TI, and they required significantly fewer trials for its induction. In an open-field test, ethanol treatment did not affect latency to move, steps taken, vocalizations, defecations, or escape attempts. The current findings demonstrate that early ethanol exposure can increase fearfulness and impair aspects of motor function. Importantly, the observed dysfunctions resulted from an acute ethanol exposure during the period when the major brain components are induced and patterned. The equivalent period in human development is 3-4 weeks postconception. The current findings emphasize that ethanol exposure during the early first trimester equivalent can produce neurodevelopmental disability in the offspring. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Oxidation of MnO(100) and NaMnO2 formation: Characterization of Mn2+ and Mn3+ surfaces via XPS and water TPD

    NASA Astrophysics Data System (ADS)

    Feng, Xu; Cox, David F.

    2018-09-01

    The oxidation of clean and Na precovered MnO(100) has been investigated by X-ray photoelectron spectroscopy (XPS), low energy electron diffraction (LEED) and temperature programmed desorption (TPD) of adsorbed water. XPS results indicate that Mn3O4-like and Mn2O3-like surfaces can be formed by various oxidation treatments of clean and nearly-stoichiometric MnO(100), while a NaMnO2-like surface can be produced by the oxidation of MnO(100) pre-covered with multilayers of metallic Na. Water TPD results indicate that water adsorption/desorption is sensitive to the available oxidation states of surface Mn cations, and can be used to distinguish between surfaces exposing Mn2+and Mn3+ cations, or a combination of these oxidation states. Carbon dioxide and water TPD results from the NaMnO2-like surface indicate that pre-adsorbed water blocks the uptake of CO2, while water displaces pre-adsorbed CO2. No indication of a strong reactive interaction is observed between CO2, water and the NaMnO2-like surface under the conditions of our study.

  7. Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh

    PubMed Central

    Smith, Allan H; Yunus, Mohammad; Khan, Al Fazal; Ercumen, Ayse; Yuan, Yan; Smith, Meera Hira; Liaw, Jane; Balmes, John; von Ehrenstein, Ondine; Raqib, Rubhana; Kalman, David; Alam, Dewan S; Streatfield, Peter K; Steinmaus, Craig

    2013-01-01

    Background Arsenic exposure via drinking water increases the risk of chronic respiratory disease in adults. However, information on pulmonary health effects in children after early life exposure is limited. Methods This population-based cohort study set in rural Matlab, Bangladesh, assessed lung function and respiratory symptoms of 650 children aged 7–17 years. Children with in utero and early life arsenic exposure were compared with children exposed to less than 10 µg/l in utero and throughout childhood. Because most children drank the same water as their mother had drunk during pregnancy, we could not assess only in utero or only childhood exposure. Results Children exposed in utero to more than 500 µg/l of arsenic were more than eight times more likely to report wheezing when not having a cold [odds ratio (OR) = 8.41, 95% confidence interval (CI): 1.66–42.6, P < 0.01] and more than three times more likely to report shortness of breath when walking on level ground (OR = 3.86, 95% CI: 1.09–13.7, P = 0.02) and when walking fast or climbing (OR = 3.19, 95% CI: 1.22–8.32, P < 0.01]. However, there was little evidence of reduced lung function in either exposure category. Conclusions Children with high in utero and early life arsenic exposure had marked increases in several chronic respiratory symptoms, which could be due to in utero exposure or to early life exposure, or to both. Our findings suggest that arsenic in water has early pulmonary effects and that respiratory symptoms are a better marker of early life arsenic toxicity than changes in lung function measured by spirometry. PMID:24062297

  8. Early marijuana initiation: The link between prenatal marijuana exposure, early childhood behavior, and negative adult roles.

    PubMed

    Goldschmidt, Lidush; Richardson, Gale A; Larkby, Cynthia; Day, Nancy L

    We investigated the associations among gestational factors including prenatal marijuana exposure (PME), child behavior at age 3, early age of onset of marijuana use (EAOM, <15years), and adult roles at 22years. Participants were drawn from the Maternal Health Practices and Child Development (MHPCD) Project, a longitudinal study of prenatal substance exposure in offspring who have been studied for over 22years since the prenatal phase. Data from the prenatal, birth, 3-, and 22-year phases (N=608) were used in the present study. Age of onset of offspring substance use was determined based on data from the 14-, 16-, and 22-year phases. The subjects were of lower socioeconomic status, 43% were Caucasian and the remaining were African-American, and 48% were males. Early childhood behavior was significantly (p<0.05) related to EAOM after controlling for PME, birth and childhood environmental risk factors, and Conduct Disorder. EAOM was significantly associated with negative adult roles including increased risk of being arrested (p<0.001), lower educational attainment (p<0.001), having a child without being married (p<0.05), and unemployment at 22years (p<0.001). The correlations between PME and negative adult roles and between early childhood behavior and negative adult roles were also statistically significant. Pathway analysis demonstrated that EAOM significantly mediated the associations between PME and fulfillment of adult roles and between early childhood behavior and adult roles. There are a number of intervention points that could be targeted that would have a long-term impact on lowering the probability of EAOM and less success in adult roles. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

    PubMed Central

    Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat

    2014-01-01

    Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life. PMID:24648221

  10. Estimating Air-Manganese Exposures in Two Ohio Towns ...

    EPA Pesticide Factsheets

    Manganese (Mn), a nutrient required for normal metabolic function, is also a persistent air pollutant and a known neurotoxin at high concentrations. Elevated exposures can result in a number of motor and cognitive deficits. Quantifying chronic personal exposures in residential populations studied by environmental epidemiologists can be time-consuming and expensive. We developed an approach for quantifying chronic exposures for two towns (Marietta and East Liverpool, Ohio) with elevated air Mn concentrations (air-Mn) related to ambient emissions from industrial processes. This was accomplished through the use of measured and modeled data in the communities studied. A novel approach was developed because one of the facilities lacked emissions data for the purposes of modeling. A unit emission rate was assumed over the surface area of both source facilities, and offsite concentrations at receptor residences and air monitoring sites were estimated with the American Meteorological Society/Environmental Protection Agency Regulatory Model (AERMOD). Ratios of all modeled receptor points were created, and a long-running air monitor was identified as a reference location. All ratios were normalized to the reference location. Long-term averages at all residential receptor points were calculated using modeled ratios and data from the reference monitoring location. Modeled five-year average air-Mn exposures ranged from 0.03-1.61 µg/m3 in Marietta and 0.01-6.32 µg/m3 in E

  11. Challenges to studying the health effects of early life environmental chemical exposures on children's health.

    PubMed

    Braun, Joseph M; Gray, Kimberly

    2017-12-01

    Epidemiological studies play an important role in quantifying how early life environmental chemical exposures influence the risk of childhood diseases. These studies face at least four major challenges that can produce noise when trying to identify signals of associations between chemical exposure and childhood health. Challenges include accurately estimating chemical exposure, confounding from causes of both exposure and disease, identifying periods of heightened vulnerability to chemical exposures, and determining the effects of chemical mixtures. We provide recommendations that will aid in identifying these signals with more precision.

  12. Differential Exposure to Early Childhood Education Services and Mother-Toddler Interaction

    ERIC Educational Resources Information Center

    Klebanov, P.K.; Brooks-Gunn, J.

    2008-01-01

    This study examined the associations of exposure to early childhood education (ECE) services upon 2.5-year-old children's task persistence and enthusiasm and their mothers' authoritative and authoritarian behavior and support stimulation. Families participated in the Infant Health and Development Program, an eight-site randomized comprehensive ECE…

  13. Effect of early life exposure to air pollution on development of childhood asthma.

    PubMed

    Clark, Nina Annika; Demers, Paul A; Karr, Catherine J; Koehoorn, Mieke; Lencar, Cornel; Tamburic, Lillian; Brauer, Michael

    2010-02-01

    There is increasing recognition of the importance of early environmental exposures in the development of childhood asthma. Outdoor air pollution is a recognized asthma trigger, but it is unclear whether exposure influences incident disease. We investigated the effect of exposure to ambient air pollution in utero and during the first year of life on risk of subsequent asthma diagnosis in a population-based nested case-control study. We assessed all children born in southwestern British Columbia in 1999 and 2000 (n = 37,401) for incidence of asthma diagnosis up to 34 years of age using outpatient and hospitalization records. Asthma cases were age- and sex-matched to five randomly chosen controls from the eligible cohort. We estimated each individual's exposure to ambient air pollution for the gestational period and first year of life using high-resolution pollution surfaces derived from regulatory monitoring data as well as land use regression models adjusted for temporal variation. We used logistic regression analyses to estimate effects of carbon monoxide, nitric oxide, nitrogen dioxide, particulate matter early life exposure to CO, NO, NO2, PM10, SO2, and black carbon and proximity to point sources. Traffic-related pollutants were associated with the highest risks: adjusted odds ratio = 1.08 (95% confidence interval, 1.041.12) for a 10-microg/m3 increase of NO, 1.12 (1.071.17) for a 10-microg/m3 increase in NO2, and 1.10 (1.061.13) for a 100-microg/m3 increase in CO. These data support the hypothesis that early childhood exposure to air pollutants plays a role in development of asthma.

  14. Oral methylphenidate alleviates the fine motor dysfunction caused by chronic postnatal manganese exposure in adult rats.

    PubMed

    Beaudin, Stéphane A; Strupp, Barbara J; Lasley, Stephen M; Fornal, Casimir A; Mandal, Shyamali; Smith, Donald R

    2015-04-01

    Developmental manganese (Mn) exposure is associated with motor dysfunction in children and animal models, but little is known about the underlying neurochemical mechanisms or the potential for amelioration by pharmacotherapy. We investigated whether methylphenidate (MPH) alleviates fine motor dysfunction due to chronic postnatal Mn exposure, and whether Mn exposure impairs brain extracellular dopamine (DA) and norepinephrine (NE) in the prefrontal cortex (PFC) and striatum in adult animals. Rats were orally exposed to 0 or 50 mg Mn/kg/day from postnatal day 1 until the end of the study (PND 145). The staircase test was used to assess skilled forelimb function. Oral MPH (2.5 mg/kg/day) was administered daily 1 h before staircase testing for 16 days. DA and NE levels were measured by dual probe microdialysis. Results show that Mn exposure impaired reaching and grasping skills and the evoked release of DA and NE in the PFC and striatum of adult rats. Importantly, oral MPH treatment fully alleviated the fine motor deficits in the Mn-exposed animals, but did not affect forelimb skills of control rats not exposed to Mn. These results suggest that catecholaminergic hypofunctioning in the PFC and striatum may underlie the Mn-induced fine motor dysfunction, and that oral MPH pharmacotherapy is an effective treatment approach for alleviating this dysfunction in adult animals. The therapeutic potential of MPH for the treatment of motor dysfunction in Mn-exposed children and adults appears promising pending further characterization of MPH efficacy in other functional areas (eg, attention) believed to be affected by developmental Mn exposure. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Early-life Sodium-exposure Unmasks Susceptibility to Stroke in hyperlipidemic-hypertensive Tg[hCETP]25-Rats

    PubMed Central

    Decano, Julius L.; Viereck, Jason C.; McKee, Ann C.; Hamilton, James A.; Ruiz-Opazo, Nelson; Herrera, Victoria L.M.

    2009-01-01

    Background Early-life risk factor exposure increases aortic atherosclerosis and blood pressure in humans and animal models, however, limited insight has been made into end-organ complications. Methods and Results We investigated the effects of early-life Na-exposure (0.23% vs 0.4%NaCl regular-rat chow) on vascular disease outcomes using the inbred, transgenic[hCETP]25 Dahl salt-sensitive hypertensive rat model of male-predominant coronary atherosclerosis, Tg25. Rather than the expected increased coronary heart disease, fetal 0.4%Na-exposure (≤2g-Na/2000cal/diet/day) induced adult-onset stroke in both sexes (ANOVA P<0.0001), with earlier stroke-onset in Tg25-females. Analysis of later onsets of 0.4%Na-exposure resulted in decreased stroke-risk and later stroke-onsets, despite longer 0.4%Na-exposure durations, indicating increasing risk with earlier onsets of 0.4%Na-exposure. Histological analysis of stroke+rat brains revealed cerebral cortical hemorrhagic infarctions, microhemorrhages, neuronal ischemia, microvascular injury. Ex-vivo MRI of stroke+ rat brains detected cerebral hemorrhages, microhemorrhages and ischemia with middle cerebral artery-distribution, and cerebellar non-involvement. Ultrasound micro-imaging detected carotid artery disease. Pre-stroke analysis detected neuronal ischemia, and decreased mass of isolated cerebral, but not cerebellar, microvessels. Conclusions Early-life Na-exposure exacerbated hypertension and unmasked stroke susceptibility with greater female vulnerability in hypertensive-hyperlipidemic Tg25-rats. The reproducible modeling in Tg25sp rats of carotid artery disease, cerebral hemorrhagic-infarctions, neuronal ischemia, microhemorrhages, and microvascular alterations suggests a pathogenic spectrum with causal interrelationships. This “mixed-stroke” spectrum could represent paradigms of ischemic-hemorrhagic transformation, and/or a microangiopathic basis for the association of ischemic-lesions, microhemorrhages, and strokes

  16. Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice

    PubMed Central

    Nemmar, Abderrahim; Hemeiri, Ahmed Al; Hammadi, Naser Al; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Elwasila, Mohamed; Ali, Badreldin H; Adeghate, Ernest

    2015-01-01

    Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored “moasel” tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are

  17. Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice.

    PubMed

    Nemmar, Abderrahim; Al Hemeiri, Ahmed; Al Hammadi, Naser; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Elwasila, Mohamed; Ali, Badreldin H; Adeghate, Ernest

    2015-03-01

    Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored "moasel" tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are early

  18. Occurrence of mental illness following prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study

    PubMed Central

    2012-01-01

    Background While many studies of adults with solvent exposure have shown increased risks of anxiety and depressive disorders, there is little information on the impact of prenatal and early childhood exposure on the subsequent risk of mental illness. This retrospective cohort study examined whether early life exposure to tetrachloroethylene (PCE)-contaminated drinking water influenced the occurrence of depression, bipolar disorder, post-traumatic stress disorder, and schizophrenia among adults from Cape Cod, Massachusetts. Methods A total of 1,512 subjects born between 1969 and 1983 were studied, including 831 subjects with both prenatal and early childhood PCE exposure and 547 unexposed subjects. Participants completed questionnaires to gather information on mental illnesses, demographic and medical characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure originating from the vinyl-liner of water distribution pipes was assessed using water distribution system modeling software that incorporated a leaching and transport algorithm. Results No meaningful increases in risk ratios (RR) for depression were observed among subjects with prenatal and early childhood exposure (RR: 1.1, 95% CI: 0.9-1.4). However, subjects with prenatal and early childhood exposure had a 1.8-fold increased risk of bipolar disorder (N = 36 exposed cases, 95% CI: 0.9-1.4), a 1.5-fold increased risk post-traumatic stress disorder (N = 47 exposed cases, 95% CI: 0.9-2.5), and a 2.1-fold increased risk of schizophrenia (N = 3 exposed cases, 95% CI: 0.2-20.0). Further increases in the risk ratio were observed for bipolar disorder (N = 18 exposed cases, RR; 2.7, 95% CI: 1.3-5.6) and post-traumatic stress disorder (N = 18 exposed cases, RR: 1.7, 95% CI: 0.9-3.2) among subjects with the highest exposure levels. Conclusions The results of this study provide evidence against an impact of early life exposure to PCE on the risk of depression. In contrast, the

  19. Occurrence of mental illness following prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study.

    PubMed

    Aschengrau, Ann; Weinberg, Janice M; Janulewicz, Patricia A; Romano, Megan E; Gallagher, Lisa G; Winter, Michael R; Martin, Brett R; Vieira, Veronica M; Webster, Thomas F; White, Roberta F; Ozonoff, David M

    2012-01-20

    While many studies of adults with solvent exposure have shown increased risks of anxiety and depressive disorders, there is little information on the impact of prenatal and early childhood exposure on the subsequent risk of mental illness. This retrospective cohort study examined whether early life exposure to tetrachloroethylene (PCE)-contaminated drinking water influenced the occurrence of depression, bipolar disorder, post-traumatic stress disorder, and schizophrenia among adults from Cape Cod, Massachusetts. A total of 1,512 subjects born between 1969 and 1983 were studied, including 831 subjects with both prenatal and early childhood PCE exposure and 547 unexposed subjects. Participants completed questionnaires to gather information on mental illnesses, demographic and medical characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure originating from the vinyl-liner of water distribution pipes was assessed using water distribution system modeling software that incorporated a leaching and transport algorithm. No meaningful increases in risk ratios (RR) for depression were observed among subjects with prenatal and early childhood exposure (RR: 1.1, 95% CI: 0.9-1.4). However, subjects with prenatal and early childhood exposure had a 1.8-fold increased risk of bipolar disorder (N = 36 exposed cases, 95% CI: 0.9-1.4), a 1.5-fold increased risk post-traumatic stress disorder (N = 47 exposed cases, 95% CI: 0.9-2.5), and a 2.1-fold increased risk of schizophrenia (N = 3 exposed cases, 95% CI: 0.2-20.0). Further increases in the risk ratio were observed for bipolar disorder (N = 18 exposed cases, RR; 2.7, 95% CI: 1.3-5.6) and post-traumatic stress disorder (N = 18 exposed cases, RR: 1.7, 95% CI: 0.9-3.2) among subjects with the highest exposure levels. The results of this study provide evidence against an impact of early life exposure to PCE on the risk of depression. In contrast, the results provide support for an impact

  20. Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel

    Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. Inmore » all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti

  1. Driving kids to smoke? Children's reported exposure to smoke in cars and early smoking initiation.

    PubMed

    Glover, Marewa; Scragg, Robert; Min, Sandar; Kira, Anette; Nosa, Vili; McCool, Judith; Bullen, Chris

    2011-11-01

    The health risks associated with second hand smoke (SHS) are well-known. However, little is known about exposure to SHS in cars and risk of smoking uptake. This paper investigates the association between pre-adolescents reported exposure to smoking in cars and prevalence of early stage smoking activity. Data from Keeping Kids Smokefree baseline surveys of students were used to investigate smoking status and reported exposure to smoking in cars. Log binomial regression analyses were used to investigate if reported exposure to SHS in cars was associated with smoking prevalence. 83% of 5676 students invited took part. After controlling for all variables reported exposure to smoking in cars and homes were significantly associated with increased risk of initiated smoking (RR 1.87, 95% CI 1.43-2.44, and RR 1.5, 95% CI 1.13-1.97, respectively). Exposure to smoking in cars was substantially and significantly associated with risk of current smoking (RR 3.21, 95% CI 1.45-7.08). Early smoking uptake is associated with students' reported exposure to smoking in cars which confirms the importance of protecting children from SHS. Smoking in cars is under parental control and therefore modifiable. Moreover, children's reports of SHlS exposure offer a simple way of identifying families who can be targeted for tobacco control interventions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Psychological symptoms and quality of life among residents exposed to long-term, low-dose environmental manganese (Mn)

    EPA Science Inventory

    Objective: Elevated levels of air manganese (air-Mn) exposure have been associated with adverse health effects. This study examined the relationship of air-Mn concentrations with mood and quality of life.Participants and methods: 185 residents (age mean (M)=55.13±10.88; ed...

  3. Community violence exposure in early adolescence: Longitudinal associations with hippocampal and amygdala volume and resting state connectivity.

    PubMed

    Saxbe, Darby; Khoddam, Hannah; Piero, Larissa Del; Stoycos, Sarah A; Gimbel, Sarah I; Margolin, Gayla; Kaplan, Jonas T

    2018-06-11

    Community violence exposure is a common stressor, known to compromise youth cognitive and emotional development. In a diverse, urban sample of 22 adolescents, participants reported on community violence exposure (witnessing a beating or illegal drug use, hearing gun shots, or other forms of community violence) in early adolescence (average age 12.99), and underwent a neuroimaging scan 3-5 years later (average age 16.92). Community violence exposure in early adolescence predicted smaller manually traced left and right hippocampal and amygdala volumes in a model controlling for age, gender, and concurrent community violence exposure, measured in late adolescence. Community violence continued to predict hippocampus (but not amygdala) volumes after we also controlled for family aggression exposure in early adolescence. Community violence exposure was also associated with stronger resting state connectivity between the right hippocampus (using the manually traced structure as a seed region) and bilateral frontotemporal regions including the superior temporal gyrus and insula. These resting state connectivity results held after controlling for concurrent community violence exposure, SES, and family aggression. Although this is the first study focusing on community violence in conjunction with brain structure and function, these results dovetail with other research linking childhood adversity with smaller subcortical volumes in adolescence and adulthood, and with altered frontolimbic resting state connectivity. Our findings suggest that even community-level exposure to neighborhood violence can have detectable neural correlates in adolescents. © 2018 John Wiley & Sons Ltd.

  4. Drosophila melanogaster - an embryonic model for studying behavioral and biochemical effects of manganese exposure

    PubMed Central

    Ternes, Ana Paula Lausmann; Zemolin, Ana Paula; da Cruz, Litiele Cezar; da Silva, Gustavo Felipe; Saidelles, Ana Paula Fleig; de Paula, Mariane Trindade; Wagner, Caroline; Golombieski, Ronaldo Medeiros; Flores, Érico Marlon de Moraes; Picoloto, Rochele Sogari; Pereira, Antônio Batista; Franco, Jeferson Luis; Posser, Thaís

    2014-01-01

    Embryonic animals are especially susceptible to metal exposure. Manganese (Mn) is an essential element, but in excess it can induce toxicity. In this study we used Drosophila melanogaster as an embryonic model to investigate biochemical and behavioral alterations due to Mn exposure. Flies were treated with standard medium supplemented with MnCl2 at 0.1 mM, 0.5 mM or 1 mM from the egg to the adult stage. At 0.5 mM and 1 mM Mn, newly ecloded flies showed significantly enhanced locomotor activity when assessed by negative geotaxis behavior. In addition, a significant increase in Mn levels (p < 0.0001) was observed, while Ca, Fe, Cu, Zn and S levels were significantly decreased. A significant drop in cell viability occurred in flies exposed to 1 mM Mn. There was also an induction of reactive oxygen species at 0.5 mM and 1 mM Mn (p < 0.05). At 1 mM, Mn increased Catalase (p < 0.005), Superoxide Dismutase (p < 0.005) and Hsp83 (p < 0.0001) mRNA expression, without altering Catalase or Superoxide Dismutase activity; the activity of Thioredoxin reductase and Glutatione-S-transferase enzymes was increased. Mn treatment did not alter ERK or JNK1/2 phosphorylation, but at 1 mM caused an inhibition of p38MAPK phosphorylation. Together these data suggest mechanisms of adaptation in the fly response to Mn exposure in embryonic life. PMID:26417337

  5. Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure.

    PubMed

    Salehi, Fariba; Krewski, Daniel; Mergler, Donna; Normandin, Louise; Kennedy, Greg; Philippe, Suzanne; Zayed, Joseph

    2003-09-15

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 microg/m(3). At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 microg/m(3), but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 microg/m(3) exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate.

  6. Early life trauma exposure and stress sensitivity in young children.

    PubMed

    Grasso, Damion J; Ford, Julian D; Briggs-Gowan, Margaret J

    2013-01-01

    The current study replicates and extends work with adults that highlights the relationship between trauma exposure and distress in response to subsequent, nontraumatic life stressors. The sample included 213 2-4-year-old children in which 64.3% had a history of potential trauma exposure. Children were categorized into 4 groups based on trauma history and current life stress. In a multivariate analysis of variance, trauma-exposed children with current life stressors had elevated internalizing and externalizing problems compared with trauma-exposed children without current stress and nontrauma-exposed children with and without current stressors. The trauma-exposed groups with or without current stressors did not differ on posttraumatic stress disorder symptom severity. Accounting for number of traumatic events did not change these results. These findings suggest that early life trauma exposure may sensitize young children and place them at risk for internalizing or externalizing problems when exposed to subsequent, nontraumatic life stressors.

  7. Tunable multiple emissions in manganese-concentrated sulfide through simultaneous tailoring of Mn-site coordination and Mn-Mn pair geometry

    NASA Astrophysics Data System (ADS)

    Chen, Zitao; Song, Enhai; Ye, Shi; Zhang, Qinyuan

    2017-12-01

    In contrast to generally single-band visible emission feature from Mn2+, simultaneous visible (VIS) and near-infrared (NIR) multiple emissions are demonstrated in Mn2+ concentrated sulfide (MnS) by only involving a single crystallographic site. Upon varying the Mn2+-site coordination and/or Mn-Mn pairs geometry in different structural MnS, the multiple emissions from divalent manganese can be easily tuned from 575 to 720 nm (VIS) or from 880 to 900 or 1380 nm (NIR), respectively. The excitation spectroscopy and the luminescent decay, together with crystal structural analyses, are employed to investigate the electronic transition and the excited state dynamics of these Mn2+ concentrated systems. It is found that the VIS and NIR emissions can be ascribed to the isolated Mn2+ ion and exchange coupled Mn-Mn pair center, respectively. The effect of crystal field and bridging geometry, as well as temperature on the exchange coupled Mn2+ pairs NIR emissive center, is also investigated in detail. This work not only provides keen insights into the de-excitation pathway of Mn2+-concentrated material, but also offers the possibilities of designing a novel NIR emitting source for various photonic applications.

  8. Estimation of Particulate Mass and Manganese Exposure Levels among Welders

    PubMed Central

    Hobson, Angela; Seixas, Noah; Sterling, David; Racette, Brad A.

    2011-01-01

    Background: Welders are frequently exposed to Manganese (Mn), which may increase the risk of neurological impairment. Historical exposure estimates for welding-exposed workers are needed for epidemiological studies evaluating the relationship between welding and neurological or other health outcomes. The objective of this study was to develop and validate a multivariate model to estimate quantitative levels of welding fume exposures based on welding particulate mass and Mn concentrations reported in the published literature. Methods: Articles that described welding particulate and Mn exposures during field welding activities were identified through a comprehensive literature search. Summary measures of exposure and related determinants such as year of sampling, welding process performed, type of ventilation used, degree of enclosure, base metal, and location of sampling filter were extracted from each article. The natural log of the reported arithmetic mean exposure level was used as the dependent variable in model building, while the independent variables included the exposure determinants. Cross-validation was performed to aid in model selection and to evaluate the generalizability of the models. Results: A total of 33 particulate and 27 Mn means were included in the regression analysis. The final model explained 76% of the variability in the mean exposures and included welding process and degree of enclosure as predictors. There was very little change in the explained variability and root mean squared error between the final model and its cross-validation model indicating the final model is robust given the available data. Conclusions: This model may be improved with more detailed exposure determinants; however, the relatively large amount of variance explained by the final model along with the positive generalizability results of the cross-validation increases the confidence that the estimates derived from this model can be used for estimating welder exposures

  9. Mn(II) Oxidation by the Multicopper Oxidase Complex Mnx: A Coordinated Two-Stage Mn(II)/(III) and Mn(III)/(IV) Mechanism.

    PubMed

    Soldatova, Alexandra V; Romano, Christine A; Tao, Lizhi; Stich, Troy A; Casey, William H; Britt, R David; Tebo, Bradley M; Spiro, Thomas G

    2017-08-23

    The bacterial manganese oxidase MnxG of the Mnx protein complex is unique among multicopper oxidases (MCOs) in carrying out a two-electron metal oxidation, converting Mn(II) to MnO 2 nanoparticles. The reaction occurs in two stages: Mn(II) → Mn(III) and Mn(III) → MnO 2 . In a companion study , we show that the electron transfer from Mn(II) to the low-potential type 1 Cu of MnxG requires an activation step, likely forming a hydroxide bridge at a dinuclear Mn(II) site. Here we study the second oxidation step, using pyrophosphate (PP) as a Mn(III) trap. PP chelates Mn(III) produced by the enzyme and subsequently allows it to become a substrate for the second stage of the reaction. EPR spectroscopy confirms the presence of Mn(III) bound to the enzyme. The Mn(III) oxidation step does not involve direct electron transfer to the enzyme from Mn(III), which is shown by kinetic measurements to be excluded from the Mn(II) binding site. Instead, Mn(III) is proposed to disproportionate at an adjacent polynuclear site, thereby allowing indirect oxidation to Mn(IV) and recycling of Mn(II). PP plays a multifaceted role, slowing the reaction by complexing both Mn(II) and Mn(III) in solution, and also inhibiting catalysis, likely through binding at or near the active site. An overall mechanism for Mnx-catalyzed MnO 2 production from Mn(II) is presented.

  10. Fourier transform spectroscopy of MnH and MnD

    NASA Astrophysics Data System (ADS)

    Balfour, W. J.; Launila, O.; Klynning, L.

    Two infrared band systems, centred near 846 nm and 1060 nm in both MnH and MnD have been rotationally analysed and shown to have a common lower state. The electronic transitions lie within the quintet manifold and are here designated c 5Σ-a 5Σ and b 5Πi-a 5Σ for the 846 and 1060 nm systems, respectively. In the 846 nm system in MnH all 10 main branches have been found in the 0-0 and 1-1 bands, while in MnD the data are complete only for 0-0. Satellite branches have been identified in the 1060 nm system and all spin and Λ-type doublings have been established. The number of assigned 0-0 branches in the 1060 nm system is 35 for MnH and 37 for MnD. Molecular constants have been determined for all three states involved. Λ-doubling diagrams are presented for b 5Πi state with v = 1, 2 levels in MnH and with the v = 2 level in MnD. Local perturbations in c5Σ (v = 1) in MnH are suspected to originate from the v = 3 level of b 5Πi.

  11. The Role of Prenatal Substance Exposure and Early Adversity on Parasympathetic Functioning from 3 to 6 Years of Age

    PubMed Central

    Abar, Beau; Sheinkopf, Stephen; Lester, Barry; Lagasse, Linda; Seifer, Ronald; Shankaran, Seetha; Bada-Ellzey, Henrietta; Bauer, Charles; Whitaker, Toni; Hinckley, Matt; Hammond, Jane; Higgins, Rosemary

    2014-01-01

    We employed latent growth curve analysis to examine trajectories of respiratory sinus arrhythmia (RSA) from 3 to 6 years among children with varying levels of prenatal substance exposure and early adversity. Data were drawn from a prospective longitudinal study of prenatal substance exposure that included 1,121 participants. Baseline RSA and RSA reactivity to an attention-demanding task were assessed at 3, 4, 5, and 6 years. Overall, there were significant individual differences in the trajectories of RSA reactivity, but not baseline RSA, across development. Greater levels of prenatal substance exposure, and less exposure to early adversity, were associated with increased RSA reactivity at 3 years, but by 6 years, both were associated with greater RSA reactivity. Prenatal substance exposure had an indirect influence through early adversity on growth in RSA reactivity. Results are in support of and contribute to the framework of allostatic load. PMID:24002807

  12. Prenatal exposure to diurnal temperature variation and early childhood pneumonia.

    PubMed

    Zeng, Ji; Lu, Chan; Deng, Qihong

    2017-04-01

    Childhood pneumonia is one of the leading single causes of mortality and morbidity in children worldwide, but its etiology still remains unclear. We investigate the association between childhood pneumonia and exposure to diurnal temperature variation (DTV) in different timing windows. We conducted a prospective cohort study of 2,598 children aged 3-6 years in Changsha, China. The lifetime prevalence of pneumonia was assessed by a questionnaire administered by the parents. Individual exposure to DTV during both prenatal and postnatal periods was estimated. Logic regression models was used to examine the association between childhood pneumonia and DTV exposure in terms of odds ratios (OR) and 95% confidence interval (CI). Lifetime prevalence of childhood pneumonia in preschool children in Changsha was high up to 38.6%. We found that childhood pneumonia was significantly associated with prenatal DTV exposure, with adjusted OR (95%CI) =1.19 (1.02-1.38), particularly during the second trimester. However, childhood pneumonia not associated with postnatal DTV exposure. Sensitivity analysis indicated that boys are more susceptible to the pneumonia risk of diurnal temperature variation than girls. We further observed that the prevalence of childhood pneumonia was decreased in recent years as DTV shrinked. Early childhood pneumonia was associated with prenatal exposure to the diurnal temperature variation (DTV) during pregnancy, particularly in the second trimester, which suggests fetal origin of childhood pneumonia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Sucrose exposure in early life alters adult motivation and weight gain.

    PubMed

    Frazier, Cristianne R M; Mason, Peggy; Zhuang, Xiaoxi; Beeler, Jeff A

    2008-09-17

    The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.

  14. Motoric impairment following manganese exposure in asteroid echinoderms.

    PubMed

    Sköld, Helen Nilsson; Baden, Susanne P; Looström, Jakob; Eriksson, Susanne P; Hernroth, Bodil E

    2015-10-01

    In the oceans, naturally occurring manganese (Mn) is released from the sediments during events of hypoxia. While neuro- and immuno-toxic effects of bioavailable manganese are well documented for crustaceans, studies of similar effects of manganese on other marine invertebrates are comparatively few. Here, we developed a new functional test "the repeated turning assay" to investigate if manganese exposure at ∼12 mg L(-1) affected motoric behaviour of two asteroid echinoderms, the Common sea star, Asterias rubens, and the Black brittle star, Ophiocomina nigra. By measuring of the turning-over capacity, from dorsal to ventral position, after one and two weeks of manganese exposure, we showed that for both species Mn exposure significantly delayed the ability to turn. After a recovery period of two weeks, the capacity of turning-over was not restored to that of unexposed animals neither for A. rubens nor for O. nigra. Further investigation of sea stars showed that Mn accumulated ∼5 fold in the tube feet, organs involved in their turning-over activity, and the high concentration remained after the recovery period. In the tube feet we also recorded an increased activity of acetylcholinesterase (AChE), here used as a proxy for neuromuscular disturbances. The results indicated that Mn induces neuromuscular disturbance in echinoderms which is important news, given that previous studies have concluded that adult echinoderms are relatively tolerant to Mn. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Perpendicular magnetic tunnel junctions with Mn-modified ultrathin MnGa layer

    NASA Astrophysics Data System (ADS)

    Suzuki, K. Z.; Miura, Y.; Ranjbar, R.; Bainsla, L.; Ono, A.; Sasaki, Y.; Mizukami, S.

    2018-02-01

    Perpendicular magnetic tunnel junctions (p-MTJs) with a MgO barrier and a 1-nm-thick MnGa electrode were investigated by inserting several monolayers (MLs) of Mn. The tunnel magnetoresistance (TMR) ratio systematically increased when increasing the Mn layer thickness with a maximum of 18 (38.4)% at 300 (5) K for a Mn layer thickness of 0.6-0.8 nm. This ratio is five times higher compared to that without the Mn layer. The perpendicular magnetic anisotropy (PMA) field and the PMA constant of the ultrathin MnGa layer also increased up to 62-90 kOe and 6.2-11.3 Merg/cm3, respectively, with an increase in the Mn interlayer thickness, even for the ultrathin regime of the MnGa layer. For p-MTJs showing a high TMR and PMA, electron microscopy indicated the presence of 3-4 MLs of Mn at the MnGa/MgO interface; thus, the Mn modification enhanced the TMR as well as improved the PMA. This may be a promising finding to develop a Mn-based free layer for spin-transfer-torque devices for high-recording-density magnetoresistive random access memory and a sub-THz oscillator/detector.

  16. Life course exposure to smoke and early menopause and menopausal transition.

    PubMed

    Tawfik, Hebatullah; Kline, Jennie; Jacobson, Judith; Tehranifar, Parisa; Protacio, Angeline; Flom, Julie D; Cirillo, Piera; Cohn, Barbara A; Terry, Mary Beth

    2015-10-01

    Early age at menopause is associated with increased risk of cardiovascular disease, stroke, osteoporosis, and all-cause mortality. Cigarette smoke exposure in adulthood is an established risk factor for earlier age at natural menopause and may be related to age at the menopausal transition. Using data from two US birth cohorts, we examined the association between smoke exposure at various stages of the life course (prenatal exposure, childhood exposure to parental smoking, and adult smoke exposure) and menopause status in 1,001 women aged 39 to 49 years at follow-up. We used logistic regression analysis (adjusting for age at follow-up) to estimate odds ratios (ORs) and 95% confidence intervals (CI) relating smoke exposure to natural menopause and the menopausal transition. The magnitudes of the associations for natural menopause were similar but not statistically significant after adjustment for confounders among (i) women with prenatal smoke exposure who did not smoke on adult follow-up (OR, 2.7; 95% CI, 0.8-9.4) and (ii) current adult smokers who were not exposed prenatally (OR, 2.8; 95% CI, 0.9-9.0). Women who had been exposed to prenatal smoke and were current smokers had three times the risk of experiencing earlier natural menopause (adjusted OR, 3.4; 95% CI, 1.1-10.3) compared with women without smoke exposure in either period. Only current smoking of long duration (>26 y) was associated with the timing of the menopausal transition. Our data suggest that exposure to smoke both prenatally and around the time of menopause accelerates ovarian aging.

  17. Preconception and early pregnancy air pollution exposures and risk of gestational diabetes mellitus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Robledo, Candace A.; Mendola, Pauline, E-mail: pauline.mendola@mail.nih.gov; Yeung, Edwina

    Background: Air pollution has been linked to gestational diabetes mellitus (GDM) but no studies have evaluated impact of preconception and early pregnancy air pollution exposures on GDM risk. Methods: Electronic medical records provided data on 219,952 singleton deliveries to mothers with (n=11,334) and without GDM (n=208,618). Average maternal exposures to particulate matter (PM) ≤ 2.5 μm (PM{sub 2.5}) and PM{sub 2.5} constituents, PM ≤ 10 μm (PM{sub 10}), nitrogen oxides (NO{sub x}), carbon monoxide, sulfur dioxide (SO{sub 2}) and ozone (O{sub 3}) were estimated for the 3-month preconception window, first trimester, and gestational weeks 1–24 based on modified Community Multiscalemore » Air Quality models for delivery hospital referral regions. Binary regression models with robust standard errors estimated relative risks (RR) for GDM per interquartile range (IQR) increase in pollutant concentrations adjusted for study site, maternal age and race/ethnicity. Results: Preconception maternal exposure to NO{sub X} (RR=1.09, 95% CI: 1.04, 1.13) and SO{sub 2} (RR=1.05, 1.01, 1.09) were associated with increased risk of subsequent GDM and risk estimates remained elevated for first trimester exposure. Preconception O{sub 3} was associated with lower risk of subsequent GDM (RR=0.93, 0.90, 0.96) but risks increased later in pregnancy. Conclusion: Maternal exposures to NO{sub x} and SO{sub 2} preconception and during the first few weeks of pregnancy were associated with increased GDM risk. O{sub 3} appeared to increase GDM risk in association with mid-pregnancy exposure but not in earlier time windows. These common exposures merit further investigation. - Highlights: • Air pollution may be related to gestational diabetes (GDM). • No prior studies have examined preconception exposure. • Maternal exposure to NO{sub x} and SO{sub 2} before conception increased subsequent GDM risk. • NO{sub x} and SO{sub 2} exposure in the first seven weeks of pregnancy also

  18. Buccal mucosa micronuclei counts in relation to exposure to low dose-rate radiation from the Chornobyl nuclear accident and other medical and occupational radiation exposures.

    PubMed

    Bazyka, D; Finch, S C; Ilienko, I M; Lyaskivska, O; Dyagil, I; Trotsiuk, N; Gudzenko, N; Chumak, V V; Walsh, K M; Wiemels, J; Little, M P; Zablotska, L B

    2017-06-23

    Ionizing radiation is a well-known carcinogen. Chromosome aberrations, and in particular micronuclei represent an early biological predictor of cancer risk. There are well-documented associations of micronuclei with ionizing radiation dose in some radiation-exposed groups, although not all. That associations are not seen in all radiation-exposed groups may be because cells with micronuclei will not generally pass through mitosis, so that radiation-induced micronuclei decay, generally within a few years after exposure. Buccal samples from a group of 111 male workers in Ukraine exposed to ionizing radiation during the cleanup activities at the Chornobyl nuclear power plant were studied. Samples were taken between 12 and 18 years after their last radiation exposure from the Chornobyl cleanup. The frequency of binucleated micronuclei was analyzed in relation to estimated bone marrow dose from the cleanup activities along with a number of environmental/occupational risk factors using Poisson regression adjusted for overdispersion. Among the 105 persons without a previous cancer diagnosis, the mean Chornobyl-related dose was 59.5 mSv (range 0-748.4 mSv). There was a borderline significant increase in micronuclei frequency among those reporting work as an industrial radiographer compared with all others, with a relative risk of 6.19 (95% CI 0.90, 31.08, 2-sided p = 0.0729), although this was based on a single person. There was a borderline significant positive radiation dose response for micronuclei frequency with increase in micronuclei per 1000 scored cells per Gy of 3.03 (95% CI -0.78, 7.65, 2-sided p = 0.1170), and a borderline significant reduction of excess relative MN prevalence with increasing time since last exposure (p = 0.0949). There was a significant (p = 0.0388) reduction in MN prevalence associated with bone X-ray exposure, but no significant trend (p = 0.3845) of MN prevalence with numbers of bone X-ray procedures. There are indications of

  19. Inhibition of ATPase activity in rat synaptic plasma membranes by simultaneous exposure to metals.

    PubMed

    Carfagna, M A; Ponsler, G D; Muhoberac, B B

    1996-03-08

    Inhibition of Na+/K+-ATPase and Mg2+-ATPase activities by in vitro exposure to Cd2+, Pb2+ and Mn2+ was investigated in rat brain synaptic plasma membranes (SPMs). Cd2+ and Pb2+ produced a larger maximal inhibition of Na+/K+-ATPase than of Mg2+-ATPase activity. Metal concentrations causing 50% inhibition of Na+/K+-ATPase activity (IC50 values) were Cd2+ (0.6 microM) < Pb2+ (2.1 microM) < Mn2+ (approximately 3 mM), and the former two metals were substantially more potent in inhibiting SPM versus synaptosomal Na+/K+-ATPase. Dixon plots of SPM data indicated that equilibrium binding of metals occurs at sites causing enzyme inhibition. In addition, IC50 values for SPM K+-dependent p-nitrophenylphosphatase inhibition followed the same order and were Cd2+ (0.4 microM) < Pb2+ (1.2 microM) < Mn2+ (300 microM). Simultaneous exposure to the combinations Cd2+/Mn2+ or Pb2+/Mn2+ inhibited SPM Na+/K+-ATPase activity synergistically (i.e., greater than the sum of the metal-induced inhibitions assayed separately), while Cd2+/Pb2+ caused additive inhibition. Simultaneous exposure to Cd2+/Pb2+ antagonistically inhibited Mg2+-ATPase activity while Cd2+/Mn2+ or Pb2+/Mn2+ additively inhibited Mg2+-ATPase activity at low Mn2+ concentrations, but inhibited antagonistically at higher concentrations. The similar IC50 values for Cd2+ and Pb2+ versus Mn2+ inhibition of Na+/K+-ATPase and the pattern of inhibition/activation upon exposure to two metals simultaneously support similar modes of interaction of Cd2+ and Pb2+ with this enzyme, in agreement with their chemical reactivities.

  20. Characterization of air manganese exposure estimates for residents in two Ohio towns

    PubMed Central

    Colledge, Michelle A.; Julian, Jaime R.; Gocheva, Vihra V.; Beseler, Cheryl L.; Roels, Harry A.; Lobdell, Danelle T.; Bowler, Rosemarie M.

    2016-01-01

    This study was conducted to derive receptor-specific outdoor exposure concentrations of total suspended particulate (TSP) and respirable (dae ≤ 10 μm) air manganese (air-Mn) for East Liverpool and Marietta (Ohio) in the absence of facility emissions data, but where long-term air measurements were available. Our “site-surface area emissions method” used U.S. Environmental Protection Agency’s (EPA) AERMOD (AMS/EPA Regulatory Model) dispersion model and air measurement data to estimate concentrations for residential receptor sites in the two communities. Modeled concentrations were used to create ratios between receptor points and calibrated using measured data from local air monitoring stations. Estimated outdoor air-Mn concentrations were derived for individual study subjects in both towns. The mean estimated long-term air-Mn exposure levels for total suspended particulate were 0.35 μg/m3 (geometric mean [GM]) and 0.88 μg/m3 (arithmetic mean [AM]) in East Liverpool (range: 0.014–6.32 μg/m3) and 0.17 μg/m3 (GM) and 0.21 μg/m3 (AM) in Marietta (range: 0.03–1.61 μg/m3). Modeled results compared well with averaged ambient air measurements from local air monitoring stations. Exposure to respirable Mn particulate matter (PM10; PM <10 μm) was higher in Marietta residents. Implications Few available studies evaluate long-term health outcomes from inhalational manganese (Mn) exposure in residential populations, due in part to challenges in measuring individual exposures. Local long-term air measurements provide the means to calibrate models used in estimating long-term exposures. Furthermore, this combination of modeling and ambient air sampling can be used to derive receptor-specific exposure estimates even in the absence of source emissions data for use in human health outcome studies. PMID:26211636

  1. Radioprotection of the Brain White Matter by Mn(III) N-Butoxyethylpyridylporphyrin-Based Superoxide Dismutase Mimic MnTnBuOE-2-PyP5+

    PubMed Central

    Weitzel, Douglas H.; Tovmasyan, Artak; Ashcraft, Kathleen A.; Rajic, Zrinka; Weitner, Tin; Liu, Chunlei; Li, Wei; Buckley, Anne F.; Prasad, Mark R.; Young, Kenneth H.; Rodriguiz, Ramona M.; Wetsel, William C.; Peters, Katherine B.; Spasojevic, Ivan; Herndon, James E.; Batinic-Haberle, Ines; Dewhirst, Mark W.

    2015-01-01

    Cranial irradiation is a standard therapy for primary and metastatic brain tumors. A major drawback of radiotherapy (RT), however, is long-term cognitive loss that affects quality of life. Radiation-induced oxidative stress in normal brain tissue is thought to contribute to cognitive decline. We evaluated the effectiveness of a novel mimic of superoxide dismutase enzyme (SOD), MnTnBuOE-2-PyP5+ (Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin), to provide long-term neuroprotection following 8 Gy of whole brain irradiation. Long-term RT damage can only be assessed by brain imaging and neurocognitive studies. C57BL/6J mice were treated with MnTnBuOE-2-PyP5+ before and after RT and evaluated three months later. At this time point, drug concentration in the brain was 25 nmol/L. Mice treated with MnTnBuOE-2-PyP5+/RT exhibited MRI evidence for myelin preservation in the corpus callosum compared with saline/RT treatment. Corpus callosum histology demonstrated a significant loss of axons in the saline/RT group that was rescued in the MnTnBuOE-2-PyP5+/RT group. In addition, the saline/RT groups exhibited deficits in motor proficiency as assessed by the rotorod test and running wheel tests. These deficits were ameliorated in groups treated with MnTnBuOE-2-PyP5+/RT. Our data demonstrate that MnTnBuOE-2-PyP5+ is neuroprotective for oxidative stress damage caused by radiation exposure. In addition, glioblastoma cells were not protected by MnTnBuOE-2-PyP5+ combination with radiation in vitro. Likewise, the combination of MnTnBuOE-2-PyP5+ with radiation inhibited tumor growth more than RT alone in flank tumors. In summary, MnTnBuOE-2-PyP5+ has dual activity as a neuroprotector and a tumor radiosensitizer. Thus, it is an attractive candidate for adjuvant therapy with RT in future studies with patients with brain cancer. PMID:25319393

  2. Repeated Exposure to Ketamine-Xylazine during Early Development Impairs Motor Learning-dependent Dendritic Spine Plasticity in Adulthood

    PubMed Central

    Huang, Lianyan; Yang, Guang

    2014-01-01

    Background Recent studies in rodents suggest that repeated and prolonged anesthetic exposure at early stages of development leads to cognitive and behavioral impairments later in life. However, the underlying mechanism remains unknown. In this study, we tested whether exposure to general anesthesia during early development will disrupt the maturation of synaptic circuits and compromise learning-related synaptic plasticity later in life. Methods Mice received ketamine/xylazine (20/3 mg/kg) anesthesia for one or three times, starting at either early [postnatal day 14 (P14)] or late (P21) stages of development (n=105). Control mice received saline injections (n=34). At P30, mice were subjected to rotarod motor training and fear conditioning. Motor learning-induced synaptic remodeling was examined in vivo by repeatedly imaging fluorescently-labeled postsynaptic dendritic spines in the primary motor cortex before and after training using two-photon microscopy. Results Three exposures to ketamine/xylazine anesthesia between P14–18 impair the animals’ motor learning and learning-dependent dendritic spine plasticity [new spine formation, 8.4 ± 1.3% (mean ± SD) versus 13.4 ± 1.8%, P = 0.002] without affecting fear memory and cell apoptosis. One exposure at P14 or three exposures between P21–25 has no effects on the animals’ motor learning or spine plasticity. Finally, enriched motor experience ameliorates anesthesia-induced motor learning impairment and synaptic deficits. Conclusion Our study demonstrates that repeated exposures to ketamine/xylazine during early development impair motor learning and learning-dependent dendritic spine plasticity later in life. The reduction in synaptic structural plasticity may underlie anesthesia-induced behavioral impairment. PMID:25575163

  3. Effects of manganese exposure on visuoperception and visual memory in schoolchildren.

    PubMed

    Hernández-Bonilla, D; Escamilla-Núñez, C; Mergler, D; Rodríguez-Dozal, S; Cortez-Lugo, M; Montes, S; Tristán-López, L A; Catalán-Vázquez, M; Schilmann, A; Riojas-Rodriguez, Horacio

    2016-12-01

    Manganese (Mn) is an essential metal involved in multiple physiological functions. Environmental exposure to airborne Mn is associated with neurocognitive deficits in humans. Children, whose nervous system is in development, are particularly susceptible to Mn neurotoxicity. The objective of this study was to assess the association between Mn environmental exposure, and effects on visuoperception and visual memory in schoolchildren. We assessed schoolchildren between 7 and 11 years old, with similar socioeconomic status, from the mining district of Molango (n=148) and Agua Blanca (n=119, non-mining area) in Hidalgo state, Mexico. The Rey-Osterrieth Complex Figure (ROCF) test was used to assess visuoperception and short-term visual memory. Hair manganese (MnH) concentrations were determined. Linear regression models were constructed to estimate the associations between MnH and ROCF scores, adjusted for potential confounders. The geometric mean MnH was nine times higher in schoolchildren from the Mn mining area (5.25μg/g) than in schoolchildren from the non-mining area (0.55μg/g). For the ROCF Copy trial, MnH was significantly associated with an increase in distortion errors (tangency, closure), angle errors, overtracing (partial overtracing). In the Immediate Recall trial, MnH was significantly associated with increased overtracing (partial overtracing) and omissions, and negatively associated with the number of perceptual drawn units, total score and percentage immediate recall. MnH is associated with alterations in visuoperception and short-term visual memory in schoolchildren exposed to airborne Mn. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. The Long-Term Impacts of Medicaid Exposure in Early Childhood: Evidence from the Program's Origin*

    PubMed Central

    Boudreaux, Michel H.; Golberstein, Ezra; McAlpine, Donna D.

    2016-01-01

    This paper examines the long-term impact of exposure to Medicaid in early childhood on adult health and economic status. The staggered timing of Medicaid's adoption across the states created meaningful variation in cumulative exposure to Medicaid for birth cohorts that are now in adulthood. Analyses of the Panel Study of Income Dynamics suggest exposure to Medicaid in early childhood (age 0-5) is associated with statistically significant and meaningful improvements in adult health (age 25-54), and this effect is only seen in subgroups targeted by the program. Results for economic outcomes are imprecise and we are unable to come to definitive conclusions. Using separate data we find evidence of two mechanisms that could plausibly link Medicaid's introduction to long-term outcomes: contemporaneous increases in health services utilization for children and reductions in family medical debt. PMID:26763123

  5. Transcriptomic Responses During Early Development Following Arsenic Exposure in Western Clawed Frogs, Silurana tropicalis.

    PubMed

    Zhang, Jing; Koch, Iris; Gibson, Laura A; Loughery, Jennifer R; Martyniuk, Christopher J; Button, Mark; Caumette, Guilhem; Reimer, Kenneth J; Cullen, William R; Langlois, Valerie S

    2015-12-01

    Arsenic compounds are widespread environmental contaminants and exposure elicits serious health issues, including early developmental anomalies. Depending on the oxidation state, the intermediates of arsenic metabolism interfere with a range of subcellular events, but the fundamental molecular events that lead to speciation-dependent arsenic toxicity are not fully elucidated. This study therefore assesses the impact of arsenic exposure on early development by measuring speciation and gene expression profiles in the developing Western clawed frog (Silurana tropicalis) larvae following the environmental relevant 0.5 and 1 ppm arsenate exposure. Using HPLC-ICP-MS, arsenate, dimethylarsenic acid, arsenobetaine, arsenocholine, and tetramethylarsonium ion were detected. Microarray and pathway analyses were utilized to characterize the comprehensive transcriptomic responses to arsenic exposure. Clustering analysis of expression data showed distinct gene expression patterns in arsenate treated groups when compared with the control. Pathway enrichment revealed common biological themes enriched in both treatments, including cell signal transduction, cell survival, and developmental pathways. Moreover, the 0.5 ppm exposure led to the enrichment of pathways and biological processes involved in arsenic intake or efflux, as well as histone remodeling. These compensatory responses are hypothesized to be responsible for maintaining an in-body arsenic level comparable to control animals. With no appreciable changes observed in malformation and mortality between control and exposed larvae, this is the first study to suggest that the underlying transcriptomic regulations related to signal transduction, cell survival, developmental pathways, and histone remodeling may contribute to maintaining ongoing development while coping with the potential arsenic toxicity in S. tropicalis during early development. © The Author 2015. Published by Oxford University Press on behalf of the

  6. Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development

    PubMed Central

    Brown, Traci A.; Holian, Andrij; Pinkerton, Kent E.; Lee, Joong Won; Cho, Yoon Hee

    2016-01-01

    Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual’s lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development. PMID:27138493

  7. Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development.

    PubMed

    Brown, Traci Ann; Holian, Andrij; Pinkerton, Kent E; Lee, Joong Won; Cho, Yoon Hee

    2016-07-01

    Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual's lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.

  8. Predicting Lactational and Early Post-Weaning Exposures in Rats Using Biologically Based Pharmacokinetic Modeling

    EPA Science Inventory

    Risk and safety assessments for early life exposures to environmental chemicals or pharmaceuticals based on cross-species extrapolation would greatly benefit from information on chemical dosimetry in the young.

  9. In utero arsenic exposure induces early onset of atherosclerosis in ApoE−/− mice

    PubMed Central

    Srivastava, Sanjay; D’Souza, Stanley E.; Sen, Utpal; States, J. Christopher

    2007-01-01

    Consumption of arsenic contaminated drinking water has been linked to higher rates of coronary disease, stroke, and peripheral arterial disease. Recent evidence suggests that early life exposures may play a significant role in the onset of chronic adult diseases. To investigate the potential for in utero exposure to accelerate the onset of cardiovascular disease we exposed pregnant ApoE-knockout (ApoE−/−) mice to arsenic in their drinking water and examined the aortic trees of their male offspring for evidence of early disease 10 and 16 weeks after birth. Mice were maintained on normal chow after weaning. ApoE−/− mice are a commonly used model for atherogenesis and spontaneously develop atherosclerotic disease. Mice exposed to arsenic in utero showed a >2-fold increase in lesion formation in the aortic roots as well as the aortic arch compared to control mice at both 10 and 16 weeks of age. The mice exposed to arsenic also had a 20 – 40% decrease in total triglycerides, but no change in total cholesterol, phospholipids and total abundance of VLDL or HDL particles. Subfractionation of VLDL particles showed a decrease in large VLDL particles. In addition, the arsenic exposed mice showed a vasorelaxation defect in response to acetylcholine suggesting disturbance of endothelial cell signalling. These results indicate that in utero arsenic exposure induces an early onset of atherosclerosis in ApoE−/− mice without a hyperlipidemic diet and support the hypothesis that in utero arsenic exposure may be atherogenic in humans. PMID:17317095

  10. Prenatal corticosteroid exposure alters early developmental seizures and behavior

    PubMed Central

    Velíšek, Libor

    2011-01-01

    In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hydrocortisone (2× 10 mg/kg), betamethasone (2× 0.4 mg/kg) or vehicle. On postnatal day (P)15, seizures were induced by flurothyl or kainic acid (3.5 or 5.0 mg/kg). Horizontal bar holding was determined prior to seizures and again on P17. Performance in the elevated plus maze was assessed on P20-22. Prenatal exposure to betamethasone decreased postnatal susceptibility to flurothyl-induced clonic seizures but not to kainic acid-induced seizures. Prenatal hydrocortisone decreased postnatal weight but did not affect seizure susceptibility. Hydrocortisone alone did not affect performance in behavioral tests except for improving horizontal bar holding on P17. A combination of prenatal hydrocortisone and postnatal seizures resulted in increased anxiety. Prenatal exposure to mineralocorticoid receptor blocker canrenoic acid did not attenuate, but surprisingly amplified the effects of hydrocortisone on body weight and significantly worsened horizontal bar performance. Thus, prenatal exposure to excess corticosteroids alters postnatal seizure susceptibility and behaviors. Specific effects may depend on corticosteroid species. PMID:21429712

  11. Examination of age-related epigenetic changes following early-life exposure to dichloroacetic acid

    EPA Science Inventory

    Recent studies have shown that transient early-life exposure to dichloroacetic acid (DCA), a pyruvate analog and metabolic reprogramming agent, increases liver cancer incidence in older mice. This carcinogenic effect is not associated with direct mutagenicity, persistent cytotoxi...

  12. Ordovician reef-hosted Jiaodingshan Mn-Co deposit and Dawashan Mn deposit, Sichuan Province, China

    USGS Publications Warehouse

    Fan, Delian; Hein, James R.; Ye, Jie

    1999-01-01

    The Jiaodingshan Mn-Co and Dawashan Mn deposits are located in the approximately 2-m thick Daduhe unit of the Wufengian strata of Late Ordovician (Ashgill) age. Paleogeographic reconstruction places the deposits at the time of their formation in a gulf between Chengdu submarine rise and the Kangdian continent. The Jiaodingshan and Dawashan deposits occur in algal-reef facies, the former in an atoll-like structure and the latter in a pinnacle reef. Ores are mainly composed of rhodochrosite, kutnahorite, hausmannite, braunite, manganosite, and bementite. Dark red, yellowish-pink, brown, green-gray, and black ores are massive, banded, laminated, spheroidal, and cryptalgal (oncolite, stromatolite, algal filaments) boundstones. Blue, green, and red algal fossils show in situ growth positions. Samples of high-grade Jiaodingshan and Dawashan ores assay as much as 66.7% MnO. Jiaodingshan Mn carbonate ores have mean contents of Ba, Co, and Pb somewhat higher than in Dawashan ores. Cobalt is widely distributed and strongly enriched in all rock types as compared to its crustal mean content. Cobalt is correlated with Cu, Ni, and MgO in both deposits and additionally with Ba and Zn in the Dawashan deposit. The δ13C(PDB) values of Mn carbonate ores (-7.8 to -16.3‰) indicate contributions of carbon from both seawater bicarbonate and the bacterial degradation of organic matter, the latter being 33% to 68%, assuming about -24‰ for the δ13C(PDB) of the organic matter. Host limestones derived carbon predominantly from seawater bicarbonate δ1313C(PDB) of +0.2 to -7‰). NW-trending fault zones controlled development of lithofacies, whereas NE-trending fault zones provided pathways for movement of fluids. The source of Co, Ni, and Cu was mainly from weathering of mafic and ultramafic rocks on the Kangdian continent, whereas contemporaneous volcanic eruptions were of secondary importance. The reefs were likely mineralized during early diagenesis under shallow burial. The reefs

  13. A tissue dose-based comparative exposure assessment of manganese using physiologically based pharmacokinetic modeling—The importance of homeostatic control for an essential metal

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gentry, P. Robinan, E-mail: rgentry@ramboll.com

    A physiologically-based pharmacokinetic (PBPK) model (Schroeter et al., 2011) was applied to simulate target tissue manganese (Mn) concentrations following occupational and environmental exposures. These estimates of target tissue Mn concentrations were compared to determine margins of safety (MOS) and to evaluate the biological relevance of applying safety factors to derive acceptable Mn air concentrations. Mn blood concentrations measured in occupational studies permitted verification of the human PBPK models, increasing confidence in the resulting estimates. Mn exposure was determined based on measured ambient air Mn concentrations and dietary data in Canada and the United States (US). Incorporating dietary and inhalation exposuresmore » into the models indicated that increases in target tissue concentrations above endogenous levels only begin to occur when humans are exposed to levels of Mn in ambient air (i.e. > 10 μg/m{sup 3}) that are far higher than those currently measured in Canada or the US. A MOS greater than three orders of magnitude was observed, indicating that current Mn air concentrations are far below concentrations that would be required to produce the target tissue Mn concentrations associated with subclinical neurological effects. This application of PBPK modeling for an essential element clearly demonstrates that the conventional application of default factors to “convert” an occupational exposure to an equivalent continuous environmental exposure, followed by the application of safety factors, is not appropriate in the case of Mn. PBPK modeling demonstrates that the relationship between ambient Mn exposures and dose-to-target tissue is not linear due to normal tissue background levels and homeostatic controls. - Highlights: • Manganese is an essential nutrient, adding complexity to its risk assessment. • Nonlinearities in biological processes are important for manganese risk assessment. • A PBPK model was used to estimate target

  14. Early pregnancy exposure to feto-toxic medications among out-patients in Malawi.

    PubMed

    Kabuluzi, Ezereth; Campbell, Malcolm; McGowan, Linda; Chirwa, Ellen; Brabin, Loretta

    2014-08-01

    To estimate the proportion of women in early pregnancy prescribed potentially feto-toxic medications at an out-patient clinic in Malawi. Over six-months the number of women of child-bearing age attending out-patient clinics and prescribed medicines at Mitundu Community Hospital was derived from the hospital's registry and pharmacy records. Women prescribed potentially feto-toxic medicines (using Food and Drug Administration classifications) by medical assessments were subsequently interviewed and pregnancy tested. Exposure to potentially feto-toxic medications was estimated and differences between pregnant and non-pregnant women were described. Of 8970 female outpatients, 1012 (11.3%; 95% CI: 10.6% to 12%) were prescribed potentially feto-toxic medicines. After excluding 740 as unlikely to be pregnant, 209 women had negative pregnancy tests and 63 were confirmed as pregnant, representing one in 16 of women prescribed contraindicated medicines or between 2.8% and 3.5% of all women attending in early pregnancy. Most medicines were FDA rated C or D. Only 152 (55.9%) of these women had been asked about pregnancy and prescribing practices did not discriminate between pregnant and non-pregnant patients. Assessment and prescribing practices for women attending out-patient clinics who might be in early pregnancy were inadequate, increasing the risk of exposure to potentially feto-toxic medicines.

  15. Possible origin of photoconductivity in La0.7Ca0.3MnO3

    NASA Astrophysics Data System (ADS)

    Sagdeo, P. R.; Choudhary, R. J.; Phase, D. M.

    2010-01-01

    The effect of photon energy on the density of states near Fermi level of pulsed laser deposited La0.7Ca0.3MnO3 thin film has been studied to investigate the possible origin of change in the conductivity of these manganites upon photon exposure. For this purpose the photoelectron spectroscopy measurements were carried out using CSR beamline (BL-2) on Indus-1 synchrotron radiation source. The valance band spectra were measured at room temperature with photon energy ranging from 40 to 60 eV. We could see huge change in the density of states near Fermi level and this change is observed to be highest at 56 eV which is due to the resonance between Mn 3p to Mn 3d level. Our results suggest that the probability of electron transfer from deep Mn 3p level to Mn 3d-eg level is higher than that of Mn 3d-t2g level. It appears that this transfer of electron from deep Mn level to Mn 3d-eg level not only modifies the density of state near Fermi level but also changes the mobility of electrons by modifying the electron lattice coupling due to presence of Mn+3 Jahn-Teller ion.

  16. Occupational and environmental exposure of automobile mechanics and nonautomotive workers to airborne manganese arising from the combustion of methylcyclopentadienyl manganese tricarbonyl (MMT).

    PubMed

    Sierra, P; Loranger, S; Kennedy, G; Zayed, J

    1995-07-01

    Inhalation exposure to manganese (Mn) was measured for a group of garage mechanics and a control group of nonautomotive workers. The airborne Mn exposure of 35 garage mechanics suspected of being relatively highly exposed to Mn from MMT was measured at the workplace over one-week period. It also was measured for 30 nonautomotive workers at the University of Montreal. The environmental exposure also was measured for the two groups, as was the exposure to three other metals, aluminum (Al), iron (Fe), and zinc (Zn). At work the mechanics were exposed to Mn concentrations varying from 0.010 to 6.673 micrograms m-3 with a mean of 0.45 microgram m-5, while the control group was exposed to concentrations varying from 0.011 to 1.862 microgram m-3 with a mean of 0.04 microgram m-3. The mean environmental exposure for the two groups was similar to the Mn concentrations gathered in Montreal in 1992. Workplace concentrations of Al, Fe, and Zn also were higher for the garage mechanics. The results suggest that less than 10% of the Mn exposure of the garage mechanics was due to MMT. The levels of the metals measured were below the established limits for industrial and even environmental exposure.

  17. Early Life Exposure to Endocrine Disrupting Chemicals and Childhood Obesity and Neurodevelopment

    PubMed Central

    Braun, Joseph M.

    2017-01-01

    Endocrine disrupting chemicals (EDCs) may increase the risk of childhood diseases by disrupting hormonally mediated processes critical for growth and development during gestation, infancy, or childhood. The fetus, infant, and child may have enhanced sensitivity to environmental stressors like EDCs due to rapid development and greater exposure to some EDCs that results from their developmentally appropriate behavior, anatomy, and physiology. This review summarizes epidemiological studies examining the relations of early-life exposure to bisphenol A (BPA), phthalates, triclosan, and perfluoroalkyl substance (PFAS) with childhood neurobehavioral disorders and obesity. The available epidemiological evidence suggests that prenatal exposure to several of these ubiquitous EDCs is associated with adverse neurobehavior (BPA and phthalates) and excess adiposity or increased risk of obesity/overweight (PFAS). Quantifying the effects of EDC mixtures, improving EDC exposure assessment, reducing bias from confounding, identifying periods of heightened vulnerability, and elucidating the presence and nature of sexually dimorphic EDC effects would result in stronger inferences from epidemiological studies. Ultimately, better estimates of the causal effects of EDC exposures on child health could help identify susceptible sub-populations and lead to public health interventions to reduce these exposures. PMID:27857130

  18. Life Course Exposure to Smoke and Early Menopause and Menopausal Transition

    PubMed Central

    Tawfik, Heba; Kline, Jennie; Jacobson, Judith; Tehranifar, Parisa; Protacio, Angeline; Flom, Julie D.; Cirillo, Piera; Cohn, Barbara A.; Terry, Mary Beth

    2015-01-01

    Objective Early age at menopause is associated with increased risk of cardiovascular disease, stroke, osteoporosis and all-cause mortality. Cigarette smoke exposure in adulthood is an established risk factor for earlier age at natural menopause and may be related to age at menopausal transition. Using data from two U.S. birth cohorts, we examined the association between smoke exposure at various stages of the life course (prenatal, childhood exposure to parental smoking and adult smoke exposure) with menopause status in 1,001 women aged 39 – 49 years at follow-up. Methods We used logistic regression analysis, adjusting for age at follow-up, to estimate odds ratios (ORs) and 95% confidence intervals (CI) relating smoke exposure to natural menopause and menopausal transition. Results The magnitudes of the associations for natural menopause were similar, but not statistically significant after adjustment for confounders for i) women with prenatal smoke exposure who did not smoke at adult follow-up (OR= 2.7 [95% CI 0.8, 9.4]) and ii) current adult smokers who were not exposed prenatally (OR= 2.8 [95% CI 0.9, 9.0]). Women who had been exposed to prenatal smoke and were current smokers had three times the risk of experiencing natural menopause (adjusted OR=3.4 [95% CI 1.1, 10.3]) compared to women without smoke exposure in either time period. Only current smoking of long duration (>26 years) was associated with the timing of the menopausal transition. Conclusion Our data suggest that exposure to smoke both prenatally and around the time of menopause accelerates ovarian aging. PMID:25803667

  19. Antiferromagnetic MnN layer on the MnGa(001) surface

    NASA Astrophysics Data System (ADS)

    Guerrero-Sánchez, J.; Takeuchi, Noboru

    2016-12-01

    Spin polarized first principles total energy calculations have been applied to study the stability and magnetic properties of the MnGa(001) surface and the formation of a topmost MnN layer with the deposit of nitrogen. Before nitrogen adsorption, surface formation energies show a stable gallium terminated ferromagnetic surface. After incorporation of nitrogen atoms, the antiferromagnetic manganese terminated surface becomes stable due to the formation of a MnN layer (Mn-N bonding at the surface). Spin density distribution shows a ferromagnetic/antiferromagnetic arrangement in the first surface layers. This thermodynamically stable structure may be exploited to growth MnGa/MnN magnetic heterostructures as well as to look for exchange biased systems.

  20. Effect of early postnatal exposure to valproate on neurobehavioral development and regional BDNF expression in two strains of mice.

    PubMed

    Bath, Kevin G; Pimentel, Tiare

    2017-05-01

    Valproate has been used for over 30years as a first-line treatment for epilepsy. In recent years, prenatal exposure to valproate has been associated with teratogenic effects, limiting its use in women that are pregnant or of childbearing age. However, despite its potential detrimental effects on development, valproate continues to be prescribed at high rates in pediatric populations in some countries. Animal models allow us to test hypotheses regarding the potential effects of postnatal valproate exposure on neurobehavioral development, as well as identify potential mechanisms mediating observed effects. Here, we tested the effect of early postnatal (P4-P11) valproate exposure (100mg/kg and 200mg/kg) on motor and affective development in two strains of mice, SVE129 and C57Bl/6N. We also assessed the effect of early valproate exposure on regional BDNF protein levels, a potential target of valproate, and mediator of neurodevelopmental outcomes. We found that early life valproate exposure led to significant motor impairments in both SVE129 and C57Bl/6N mice. Both lines of mice showed significant delays in weight gain, as well as impairments in the righting reflex (P7-8), wire hang (P17), open field (P12 and P21), and rotarod (P25 and P45) tasks. Interestingly, some of the early locomotor effects were strain- and dose-dependent. We observed no effects of valproate on early markers of anxiety-like behavior. Importantly, early life valproate exposure had significant effects on regional BDNF expression, leading to a near 50% decrease in BDNF levels in the cerebellum of both strains of mice, while not impacting hippocampal BDNF protein levels. These observations indicate that postnatal exposure to valproate may have significant, and region-specific effects, on neural and behavioral development, with specific consequences for cerebellar development and motor function. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice.

    PubMed

    Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui

    2017-03-01

    Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437-446; http://dx.doi.org/10.1289/EHP360.

  2. Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice

    PubMed Central

    Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui

    2016-01-01

    Background: Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. Objectives: We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. Methods: We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Results: Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. Conclusions: An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health

  3. Imidacloprid Exposure Suppresses Neural Crest Cells Generation during Early Chick Embryo Development.

    PubMed

    Wang, Chao-Jie; Wang, Guang; Wang, Xiao-Yu; Liu, Meng; Chuai, Manli; Lee, Kenneth Ka Ho; He, Xiao-Song; Lu, Da-Xiang; Yang, Xuesong

    2016-06-15

    Imidacloprid is a neonicotinoid pesticide that is widely used in the control pests found on crops and fleas on pets. However, it is still unclear whether imidacloprid exposure could affect early embryo development-despite some studies having been conducted on the gametes. In this study, we demonstrated that imidacloprid exposure could lead to abnormal craniofacial osteogenesis in the developing chick embryo. Cranial neural crest cells (NCCs) are the progenitor cells of the chick cranial skull. We found that the imidacloprid exposure retards the development of gastrulating chick embryos. HNK-1, PAX7, and Ap-2α immunohistological stainings indicated that cranial NCCs generation was inhibited after imidacloprid exposure. Double immunofluorescent staining (Ap-2α and PHIS3 or PAX7 and c-Caspase3) revealed that imidacloprid exposure inhibited both NCC proliferation and apoptosis. In addition, it inhibited NCCs production by repressing Msx1 and BMP4 expression in the developing neural tube and by altering expression of EMT-related adhesion molecules (Cad6B, E-Cadherin, and N-cadherin) in the developing neural crests. We also determined that imidacloprid exposure suppressed cranial NCCs migration and their ability to differentiate. In sum, we have provided experimental evidence that imidacloprid exposure during embryogenesis disrupts NCCs development, which in turn causes defective cranial bone development.

  4. Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation

    PubMed Central

    Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P.; Zhou, Feng C.

    2009-01-01

    Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88 mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10 and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p < 0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes

  5. Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation.

    PubMed

    Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P; Zhou, Feng C

    2009-10-01

    Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10, and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p<0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes in

  6. Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb

    PubMed Central

    2017-01-01

    Abstract Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB. PMID:28955723

  7. Multireversible redox processes in pentanuclear bis(triple-helical) manganese complexes featuring an oxo-centered triangular {Mn(II)2Mn(III)(μ3-O)}5+ or {Mn(II)Mn(III)2(μ3-O)}6+ core wrapped by two {Mn(II)2(bpp)3}-.

    PubMed

    Romain, Sophie; Rich, Jordi; Sens, Cristina; Stoll, Thibaut; Benet-Buchholz, Jordi; Llobet, Antoni; Rodriguez, Montserrat; Romero, Isabel; Clérac, Rodolphe; Mathonière, Corine; Duboc, Carole; Deronzier, Alain; Collomb, Marie-Noëlle

    2011-09-05

    A new pentanuclear bis(triple-helical) manganese complex has been isolated and characterized by X-ray diffraction in two oxidation states: [{Mn(II)(μ-bpp)(3)}(2)Mn(II)(2)Mn(III)(μ-O)](3+) (1(3+)) and [{Mn(II)(μ-bpp)(3)}(2)Mn(II)Mn(III)(2)(μ-O)](4+) (1(4+)). The structure consists of a central {Mn(3)(μ(3)-O)} core of Mn(II)(2)Mn(III) (1(3+)) or Mn(II)Mn(III)(2) ions (1(4+)) which is connected to two apical Mn(II) ions through six bpp(-) ligands. Both cations have a triple-stranded helicate configuration, and a pair of enantiomers is present in each crystal. The redox properties of 1(3+) have been investigated in CH(3)CN. A series of five distinct and reversible one-electron waves is observed in the -1.0 and +1.50 V potential range, assigned to the Mn(II)(4)Mn(III)/Mn(II)(5), Mn(II)(3)Mn(III)(2)/Mn(II)(4)Mn(III), Mn(II)(2)Mn(III)(3)/Mn(II)(3)Mn(III)(2), Mn(II)Mn(III)(4)/Mn(II)(2)Mn(III)(3), and Mn(III)(5)/Mn(II)Mn(III)(4) redox couples. The two first oxidation processes leading to Mn(II)(3)Mn(III)(2) (1(4+)) and Mn(II)(2)Mn(III)(3) (1(5+)) are related to the oxidation of the Mn(II) ions of the central core and the two higher oxidation waves, close in potential, are thus assigned to the oxidation of the two apical Mn(II) ions. The 1(4+) and 1(5+) oxidized species and the reduced Mn(4)(II) (1(2+)) species are quantitatively generated by bulk electrolyses demonstrating the high stability of the pentanuclear structure in four oxidation states (1(2+) to 1(5+)). The spectroscopic characteristics (X-band electron paramagnetic resonance, EPR, and UV-visible) of these species are also described as well as the magnetic properties of 1(3+) and 1(4+) in solid state. The powder X- and Q-band EPR signature of 1(3+) corresponds to an S = 5/2 spin state characterized by a small zero-field splitting parameter (|D| = 0.071 cm(-1)) attributed to the two apical Mn(II) ions. At 40 K, the magnetic behavior is consistent for 1(3+) with two apical S = 5/2 {Mn(II)(bpp)(3)}(-) and one S

  8. Manganese exposure alters extracellular GABA, GABA receptor and transporter protein and mRNA levels in the developing rat brain

    PubMed Central

    Anderson, Joel G.; Fordahl, Steve C.; Cooney, Paula T.; Weaver, Tara L.; Colyer, Christa L.; Erikson, Keith M.

    2011-01-01

    Unlike other essential trace elements (e.g., zinc and iron) it is the toxicity of manganese (Mn) that is more common in human populations than its deficiency. Data suggest alterations in dopamine biology may drive the effects associated with Mn neurotoxicity, though recently γ-aminobutyric acid (GABA) has been implicated. In addition, iron deficiency (ID), a common nutritional problem, may cause disturbances in neurochemistry by facilitating accumulation of Mn in the brain. Previous data from our lab have shown decreased brain tissue levels of GABA as well as decreased 3H-GABA uptake in synaptosomes as a result of Mn exposure and ID. These results indicate a possible increase in the concentration of extracellular GABA due to alterations in expression of GABA transport and receptor proteins. In this study weanling-male Sprague-Dawley rats were randomly placed into one of four dietary treatment groups: control (CN; 35 mg Fe/kg diet), iron-deficient (ID; 6 mg Fe/kg diet), CN with Mn supplementation (via the drinking water; 1 g Mn/L) (CNMn), and ID with Mn supplementation (IDMn). Using in vivo microdialysis, an increase in extracellular GABA concentrations in the striatum was observed in response to Mn exposure and ID although correlational analysis reveals that extracellular GABA is related more to extracellular iron levels and not Mn. A diverse effect of Mn exposure and ID was observed in the regions examined via Western blot and RT-PCR analysis, with effects on mRNA and protein expression of GAT-1, GABAA, and GABAB differing between and within the regions examined. For example, Mn exposure reduced GAT-1 protein expression by approximately 50% in the substantia nigra, while increasing mRNA expression approximately four-fold, while in the caudate putamen mRNA expression was decreased with no effect on protein expression. These data suggest that Mn exposure results in an increase in extracellular GABA concentrations via altered expression of transport and receptor

  9. Sex differences in the consequences of early-life exposure to epidemiological stress--a life-history approach.

    PubMed

    Störmer, Charlotte

    2011-01-01

    Exposure to infectious disease in early life has been suggested to have a negative effect on later-life survival,possibly through the induction of inflammatory responses. Although a life-course perspective emphasizes the importance of both survival and reproduction for individual fitness, to date, no studies have investigated whether early-life exposure to infectious disease has an impact on reproduction as it has been suggested for later survival. To address this question, I have used family reconstitution data from a historical (18th and 19th century) human population in the Krummhörn (Germany) comparing survival and reproduction between an exposed and a non-exposed group. The exposed group comprised those exposed to a high-infectious disease load during prenatal and early postnatal development. The results show a marked sex difference in the impact of early-life exposure to infectious disease. Exposed females show no effect on their life expectancy but significantly reduced fertility (number of children). For exposed males, however, the effect on survival is opponent over time: mortality is increased during childhood but decreased in late adulthood. Above that, exposed males reproduce earlier and have a smaller proportion of surviving children. This study does not support former studies indicating a negative association between early-life disease load and later survival. I argue that due to differences in male and female life strategies, males in general are more vulnerable especially early in life. Hence, adverse environmental conditions may have a stronger effect on male survivability and reproductive performance.

  10. Interactive effects of early and recent exposure to stressful contexts on cortisol reactivity in middle childhood.

    PubMed

    Jaffee, Sara R; McFarquhar, Tara; Stevens, Suzanne; Ouellet-Morin, Isabelle; Melhuish, Edward; Belsky, Jay

    2015-02-01

    Given mixed findings as to whether stressful experiences and relationships are associated with increases or decreases in children's cortisol reactivity, we tested whether a child's developmental history of risk exposure explained variation in cortisol reactivity to an experimentally induced task. We also tested whether the relationship between cortisol reactivity and children's internalizing and externalizing problems varied as a function of their developmental history of stressful experiences and relationships. Participants included 400 children (M = 9.99 years, SD = 0.74 years) from the Children's Experiences and Development Study. Early risk exposure was measured by children's experiences of harsh, nonresponsive parenting at 3 years. Recent risk exposure was measured by children's exposure to traumatic events in the past year. Children's cortisol reactivity was measured in response to a social provocation task and parents and teachers described children's internalizing and externalizing problems. The effect of recent exposure to traumatic events was partially dependent upon a child's early experiences of harsh, nonresponsive parenting: the more traumatic events children had recently experienced, the greater their cortisol reactivity if they had experienced lower (but not higher) levels of harsh, nonresponsive parenting at age 3. The lowest levels of cortisol reactivity were observed among children who had experienced the most traumatic events in the past year and higher (vs. lower) levels of harsh, nonresponsive parenting in early childhood. Among youth who experienced harsh, nonresponsive parent-child relationships in early childhood and later traumatic events, lower levels of cortisol reactivity were associated with higher levels of internalizing and externalizing problems. Hypothalamic-pituitary-adrenal (HPA) axis reactivity to psychological stressors and the relationship between HPA axis reactivity and children's internalizing and externalizing

  11. Micronuclei in cord blood lymphocytes and associations with biomarkers of exposure to carcinogens and hormonally active factors, gene polymorphisms, and gene expression: the NewGeneris cohort.

    PubMed

    Merlo, Domenico Franco; Agramunt, Silvia; Anna, Lívia; Besselink, Harrie; Botsivali, Maria; Brady, Nigel J; Ceppi, Marcello; Chatzi, Leda; Chen, Bowang; Decordier, Ilse; Farmer, Peter B; Fleming, Sarah; Fontana, Vincenzo; Försti, Asta; Fthenou, Eleni; Gallo, Fabio; Georgiadis, Panagiotis; Gmuender, Hans; Godschalk, Roger W; Granum, Berit; Hardie, Laura J; Hemminki, Kari; Hochstenbach, Kevin; Knudsen, Lisbeth E; Kogevinas, Manolis; Kovács, Katalin; Kyrtopoulos, Soterios A; Løvik, Martinus; Nielsen, Jeanette K; Nygaard, Unni Cecilie; Pedersen, Marie; Rydberg, Per; Schoket, Bernadette; Segerbäck, Dan; Singh, Rajinder; Sunyer, Jordi; Törnqvist, Margareta; van Loveren, Henk; van Schooten, Frederik J; Vande Loock, Kim; von Stedingk, Hans; Wright, John; Kleinjans, Jos C; Kirsch-Volders, Micheline; van Delft, Joost H M

    2014-02-01

    Leukemia incidence has increased in recent decades among European children, suggesting that early-life environmental exposures play an important role in disease development. We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Malondialdehyde DNA adducts (M1dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M1dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX® (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX® (for estrogens) (2 genes), and DR CALUX® (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/2 and CYP2E1

  12. Estimating Air-Manganese Exposures in Two Ohio Towns

    EPA Science Inventory

    Manganese (Mn), a nutrient required for normal metabolic function, is also a persistent air pollutant and a known neurotoxin at high concentrations. Elevated exposures can result in a number of motor and cognitive deficits. Quantifying chronic personal exposures in residential po...

  13. XPS and EELS characterization of Mn2SiO4, MnSiO3 and MnAl2O4

    NASA Astrophysics Data System (ADS)

    Grosvenor, A. P.; Bellhouse, E. M.; Korinek, A.; Bugnet, M.; McDermid, J. R.

    2016-08-01

    X-ray Photoelectron Spectroscopy (XPS) and Electron Energy Loss Spectroscopy (EELS) are strong candidate techniques for characterizing steel surfaces and substrate-coating interfaces when investigating the selective oxidation and reactive wetting of advanced high strength steels (AHSS) during the continuous galvanizing process. However, unambiguous identification of ternary oxides such as Mn2SiO4, MnSiO3, and MnAl2O4 by XPS or EELS, which can play a significant role in substrate reactive wetting, is difficult due to the lack of fully characterized standards in the literature. To resolve this issue, samples of Mn2SiO4, MnSiO3 and MnAl2O4 were synthesized and characterized by XPS and EELS. The unique features of the XPS and EELS spectra for the Mn2SiO4, MnSiO3 and MnAl2O4 standards were successfully derived, thereby allowing investigators to fully differentiate and identify these oxides at the surface and subsurface of Mn, Si and Al alloyed AHSS using these techniques.

  14. Diversity of Mn oxides produced by Mn(II)-oxidizing fungi

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Santelli, Cara M.; Webb, Samuel M.; Dohnalkova, Alice

    Manganese (Mn) oxides are environmentally abundant, highly reactive mineral phases that mediate the biogeochemical cycling of nutrients, contaminants, carbon, and numerous other elements. Despite the belief that microorganisms (specifically bacteria and fungi) are responsible for the majority of Mn oxide formation in the environment, the impact of microbial species, physiology, and growth stage on Mn oxide formation is largely unresolved. Here, we couple microscopic and spectroscopic techniques to characterize the Mn oxides produced by four different species of Mn(II)-oxidizing Ascomycete fungi (Plectosphaerella cucumerina strain DS2psM2a2, Pyrenochaeta sp. DS3sAY3a, Stagonospora sp. SRC1lsM3a, and Acremonium strictum strain DS1bioAY4a) isolated from acid minemore » drainage treatment systems in central Pennsylvania. The site of Mn oxide formation varies greatly among the fungi, including deposition on hyphal surfaces, at the base of reproductive structures (e.g., fruiting bodies), and on envisaged extracellular polymers adjacent to the cell. The primary product of Mn(II) oxidation for all species growing under the same chemical and physical conditions is a nanoparticulate, poorly-crystalline hexagonal birnessite-like phase resembling synthetic d-MnO2. The phylogeny and growth conditions (planktonic versus surface-attached) of the fungi, however, impact the conversion of the initial phyllomanganate to more ordered phases, such as todorokite (A. strictum strain DS1bioAY4a) and triclinic birnessite (Stagonospora sp. SRC1lsM3a). Our findings reveal that the species of Mn(II)-oxidizing fungi impacts the size, morphology, and structure of Mn biooxides, which will likely translate to large differences in the reactivity of the Mn oxide phases.« less

  15. Exposure to Environmental Air Manganese and Medication ...

    EPA Pesticide Factsheets

    Manganese (Mn) is an essential element with natural low levels found in water, food, and air, but due to industrialized processes, both workplace and the environmental exposures to Mn have increased. Recently, environmental studies have reported physical and mental health problems associated with air-Mn exposure, but medical record reviews for exposed residents are rare in the literature. When medical records and clinical testing are unavailable, examination of residents’ prescribed medication use may be used as a surrogate of health effects associated with Mn. We examined medication use among adult Ohio residents in two towns with elevated air-Mn (n=185) and one unexposed control town (n=90). Study participants recorded medication use in a health questionnaire and brought their currently prescribed medication, over-the-counter and supplement lists to their interview. Two physicians (family and psychiatric medicine) reviewed the provided medication list and developed medical categories associated with the medications used. The exposed (E) and control (C) groups were compared on the established 12 medication and 1 supplement categories using chi-square tests. The significant medication categories were further analyzed using hierarchical binomial logistic regression adjusting for education, personal income, and years of residency. The two groups were primarily white (E:94.6%; C:96.7%) but differed on education (E:13.8; C:15.2 years), residence length in their re

  16. Linking Magazine Exposure to Social Appearance Anxiety: The Role of Appearance Norms in Early Adolescence.

    PubMed

    Trekels, Jolien; Eggermont, Steven

    2017-12-01

    Early adolescents (N = 1,591; M age  = 11.698; SD = 0.892) participated in a two-wave panel study (6-month interval) to examine the longitudinal association between appearance-focused magazine exposure and social appearance anxiety. We revealed that magazine exposure positively correlated with the internalization of appearance ideals and the attribution of social rewards to attractiveness which, in turn, related to social appearance anxiety. Internalization and attribution of social rewards formed a reinforcing spiral; once internalized, early adolescents associate positive things with appearance ideals (e.g., peer acceptance) and the perception of rewards increases early adolescents' inclination to internalize ideals. Given the adverse consequences of social appearance anxiety, the findings warrant research on the role of media in the occurrence of social appearance anxiety. © 2017 The Authors. Journal of Research on Adolescence © 2017 Society for Research on Adolescence.

  17. Unique light-induced degradation in yellow-emitting K₂SiF₆:Mn²⁺ phosphor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oyama, Takuya; Adachi, Sadao, E-mail: adachi@el.gunma-u.ac.jp

    2014-10-07

    Photo-induced luminescence intensity degradation in yellow-emitting K₂SiF₆:Mn²⁺ phosphor is studied using x-ray diffraction measurement, photoluminescence (PL) analysis, PL excitation (PLE) spectroscopy, PL decay analysis, and electron spin resonance (ESR) measurement. The yellow-emitting K₂SiF₆:Mn²⁺ phosphor exhibits remarkable degradation in the PL intensity under Xe lamp exposure. Coherent laser irradiation also induces degradation and its degree is in the order of He–Cd (λ = 325 nm) > Ar⁺ (488 nm) > He–Ne laser (632.8 nm). The degradation mechanism is proposed to be due to change in the valence state of manganese ions from Mn²⁺ to Mn³⁺ by the photooxidation (Mn²⁺ → Mn³⁺)more » or disproportionation reaction (2Mn²⁺ → Mn⁺ + Mn³⁺). The ESR measurement confirms the decreased Mn²⁺ spin density in the sample exposed with Xe lamp. The PLE spectrum suggests that the excitation of Mn³⁺ ions occurs through energy transfer upon absorption of exciting radiation by the Mn²⁺ ions. Thermal annealing of the degraded samples at ≥200 °C causes a blueshift in the PL emission band with an appearance of the Mn⁴⁺-related sharp red emission lines.« less

  18. Nano-sized Mn3O4 and β-MnOOH from the decomposition of β-cyclodextrin-Mn: 2. The water-oxidizing activities.

    PubMed

    Najafpour, Mohammad Mahdi; Mostafalu, Ramin; Hołyńska, Małgorzata; Ebrahimi, Foad; Kaboudin, Babak

    2015-11-01

    Nano-sized Mn oxides contain Mn3O4, β-MnOOH and Mn2O3 have been prepared by a previously reported method using thermal decomposition of β-cyclodextrin-Mn complexes. In the next step, the water-oxidizing activities of these Mn oxides using cerium(IV) ammonium nitrate as a chemical oxidant are studied. The turnover frequencies for β-MnO(OH) and Mn3O4 are 0.24 and 0.01-0.17 (mmol O2/mol Mns), respectively. Subsequently, water-oxidizing activities of these compounds are compared to the other previously reported Mn oxides. Important factors affecting water oxidation by these Mn oxides are also discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Fluoride Exposure in Early Life as the Possible Root Cause of Disease In Later Life.

    PubMed

    Nakamoto, Tetsuo; Rawls, H Ralph

    2018-05-15

    Fluoride, one of the most celebrated ingredients for the prevention of dental caries in the 20th century, has also been controversial for its use in dentifrices and other applications. In the current review, we have concentrated primarily on early-life exposure to fluoride and how it may affect the various organs. The most recent controversial aspects of fluoride are related to toxicity of the developing brain and how it may possibly result in the decrease of intelligence quotient (IQ), autism, and calcification of the pineal gland. In addition, it has been reported to have possible effects on bone and thyroid glands. If nutritional stress is applied during a critical period of growth and development, the organ(s) and/or body will never recover once they pass through the critical period. For example, if animals are force-fed during experiments, they will simply get fat but never reach the normal size. Although early-life fluoride exposure causing fluorosis is well reported in the literature, the dental profession considers it primarily as an esthetic rather than a serious systemic problem. In the current review, we wanted to raise the possibility of future disease as a result of early-life exposure to fluoride. It is not currently known how fluoride will become a cause of future disease. Studies of other nutritional factors have shown that the effects of early nutritional stress are a cause of disease in later life.

  20. Children's Environmental Health in the Digital Era: Understanding Early Screen Exposure as a Preventable Risk Factor for Obesity and Sleep Disorders.

    PubMed

    Wolf, Candice; Wolf, Seth; Weiss, Miriam; Nino, Gustavo

    2018-02-23

    The quantity, accessibility and focus on child-targeted programming has exponentially increased since it entered American households in the early 1900s. It may have started with the television (TV), but technology has evolved and now fits in our pockets; as of 2017, 95% of American families own a smartphone. Availability and child-tailored content has subsequently led to a decrease in the age at initial screen exposure. The negative effects that accompany the current culture of early screen exposure are extensive and need to be considered as technology continues to enter the home and inundate social interactions. Increased levels of early screen exposure have been associated with decreased cognitive abilities, decreased growth, addictive behavior, poor school performance, poor sleep patterns, and increased levels of obesity. Research on the adverse effects of early screen exposure is mounting, but further epidemiological studies are still needed to inform prevention and regulation policies.

  1. Effects of early heat exposure on thermoregulatory responses and blood viscosity of broilers prior to marketing.

    PubMed

    Zhou, W T; Fujita, M; Ito, T; Yamamoto, S

    1997-07-01

    1. This study was to determine the effects of heat load early in life on thermoregulatory responses and whole blood viscosity of broilers during a subsequent exposure to high environmental temperature later in life. 2. The birds, which had been subjected to exposure to 38 degrees C for 24 h at 5-d-old, served as prior exposure group (group A). Both group A and control group B were exposed to 33 degrees C for 3 h when near marketable weight. 3. On exposure to 33 degrees C, although there were no significant differences in the increases in heat production (HP) between the two groups, abdominal temperature (Ta), temperature of external ear tract (Tee), shank skin temperature (Tss), standing-lying frequency and lying time were lower in group A than in group B. Heart rate (HR) and comb surface temperature (Tcs) did not differ but increased in both groups during exposure to 33 degrees C. Respiration rate (RR) was greater in group A. 4. Blood viscosity decreased markedly in both groups after exposure to 33 degrees C; the decrease was greater in group A. 5. These results suggest that early exposure may promote broilers' ability to cope with the subsequent heat load by altering thermoregulatory physiological responses and behavioural patterns, resulting in an alleviation of heat stress.

  2. In utero and early childhood exposure to arsenic decreases lung function in children

    PubMed Central

    Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R. Clark; Gandolfi, A. Jay; Gonzalez-De Alba, Cesar

    2016-01-01

    Background The lung is a target organ for adverse health outcomes following exposure to arsenic. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to arsenic through drinking water, however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of arsenic and its metabolites with lung function in children exposed in utero and in early childhood to high arsenic levels through drinking water. Methods A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic arsenic. Lung function was assessed by spirometry. Results Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 μg/L. The mean urinary arsenic level registered in the studied subjects was 141.2 μg/L and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percent of inorganic arsenic. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Conclusion Exposure to arsenic through drinking water during in utero and early life was associated with a decrease in FVC and with a restrictive spirometric pattern in the children evaluated. PMID:25131850

  3. Lung Function in Rural Guatemalan Women Before and After a Chimney Stove Intervention to Reduce Wood Smoke Exposure: Results From the Randomized Exposure Study of Pollution Indoors and Respiratory Effects and Chronic Respiratory Effects of Early Childhood Exposure to Respirable Particulate Matter Study.

    PubMed

    Guarnieri, Michael; Diaz, Esperanza; Pope, Daniel; Eisen, Ellen A; Mann, Jennifer; Smith, Kirk R; Smith-Sivertsen, Tone; Bruce, Nigel G; Balmes, John R

    2015-11-01

    COPD is the third most frequent cause of death globally, with much of this burden attributable to household biomass smoke exposure in developing countries. As biomass smoke exposure is also associated with cardiovascular disease, lower respiratory infection, lung cancer, and cataracts, it presents an important target for public health intervention. Lung function in Guatemalan women exposed to wood smoke from open fires was measured throughout the Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) stove intervention trial and continued during the Chronic Respiratory Effects of Early Childhood Exposure to Respirable Particulate Matter (CRECER) cohort study. In RESPIRE, early stove households received a chimney woodstove at the beginning of the 18-month trial, and delayed stove households received a stove at trial completion. Personal exposure to wood smoke was assessed with exhaled breath carbon monoxide (CO) and personal CO tubes. Change in lung function between intervention groups and as a function of wood smoke exposure was assessed using random effects models. Of 306 women participating in both studies, acceptable spirometry was collected in 129 early stove and 136 delayed stove households (n = 265), with a mean follow-up of 5.6 years. Despite reduced wood smoke exposures in early stove households, there were no significant differences in any of the measured spirometric variables during the study period (FEV1, FVC, FEV1/FVC ratio, and annual change) after adjustment for confounding. In these young Guatemalan women, there was no association between lung function and early randomization to a chimney stove or personal wood smoke exposure. Future stove intervention trials should incorporate cleaner stoves, longer follow-up, or potentially susceptible groups to identify meaningful differences in lung function.

  4. Early visual language exposure and emergent literacy in preschool deaf children: findings from a national longitudinal study.

    PubMed

    Allen, Thomas E; Letteri, Amy; Choi, Song Hoa; Dang, Daqian

    2014-01-01

    Brief review is provided of recent research on the impact of early visual language exposure on a variety of developmental outcomes, including literacy, cognition, and social adjustment. This body of work points to the great importance of giving young deaf children early exposure to a visual language as a critical precursor to the acquisition of literacy. Four analyses of data from the Visual Language and Visual Learning (VL2) Early Education Longitudinal Study are summarized. Each confirms findings from previously published laboratory findings and points to the positive effects of early sign language on, respectively, letter knowledge, social adaptability, sustained visual attention, and cognitive-behavioral milestones necessary for academic success. The article concludes with a consideration of the qualitative similarity hypothesis and a finding that the hypothesis is valid, but only if it can be presented as being modality independent.

  5. Environmental Exposure to Manganese in Air: Associations with Tremor and Motor Function

    EPA Science Inventory

    BACKGROUND: Manganese (Mn) inhalation has been associated with neuropsychological and neurological sequelae in exposed workers. Few environmental epidemiologic studies have examined the potentialy neurotoxic effects of Mn exposure in ambient air on motor function and han...

  6. Characterization of Mn-resistant endophytic bacteria from Mn-hyperaccumulator Phytolacca americana and their impact on Mn accumulation of hybrid penisetum.

    PubMed

    Zhang, Wen-Hui; Chen, Wei; He, Lin-Yan; Wang, Qi; Sheng, Xia-Fang

    2015-10-01

    Three hundred Mn-resistant endophytic bacteria were isolated from the Mn-hyperaccumulator, Phytolacca americana, grown at different levels of Mn (0, 1, and 10mM) stress. Under no Mn stress, 90%, 92%, and 11% of the bacteria produced indole acetic acid (IAA), siderophore, and 1-aminocyclopropane-1-carboxylate (ACC) deaminase, respectively. Under Mn stress, 68-94%, 91-92%, and 21-81% of the bacteria produced IAA, siderophore, and ACC deaminase, respectively. Greater percentages of ACC deaminase-producing bacteria were found in the Mn-treated P. americana. Furthermore, the ratios of IAA- and siderophore-producing bacteria were significantly higher in the Mn treated plant leaves, while the ratio of ACC deaminase-producing bacteria was significantly higher in the Mn treated-roots. Based on 16S rRNA gene sequence analysis, Mn-resistant bacteria were affiliated with 10 genera. In experiments involving hybrid penisetum grown in soils treated with 0 and 1000mgkg(-1) of Mn, inoculation with strain 1Y31 was found to increase the root (ranging from 6.4% to 18.3%) and above-ground tissue (ranging from 19.3% to 70.2%) mass and total Mn uptake of above-ground tissues (64%) compared to the control. Furthermore, inoculation with strain 1Y31 was found to increase the ratio of IAA-producing bacteria in the rhizosphere and bulk soils of hybrid penisetum grown in Mn-added soils. The results showed the effect of Mn stress on the ratio of the plant growth-promoting factor-producing endophytic bacteria of P. americana and highlighted the potential of endophytic bacterium as an inoculum for enhanced phytoremediation of Mn-polluted soils by hybrid penisetum plants. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Early life low-level cadmium exposure is positively associated with increased oxidative stress

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kippler, Maria; Bakhtiar Hossain, Mohammad; Department of Laboratory Medicine, Section of Occupational and Environmental Medicine, Lund University, Lund

    Environmental exposure to cadmium (Cd) is known to induce oxidative stress, a state of imbalance between the production of reactive oxygen species (ROS) and the ability to detoxify them, in adults. However, data are lacking on potential effects in early-life. We evaluated urinary concentrations of 8-oxo-7,8-dihydro-2 Prime -deoxyguanosine (8-oxodG), a recognized marker of oxidative DNA damage, in relation to Cd exposure in 96 predominantly breast-fed infants (11-17 weeks of age) in rural Bangladesh. Urinary 8-oxodG was measured using liquid chromatography tandem mass spectrometry and Cd in urine and breast milk by inductively coupled plasma mass spectrometry. Median concentration of 8-oxodGmore » was 3.9 nmol/L, urinary Cd 0.30 {mu}g/L, and breast-milk Cd 0.13 {mu}g/L. In linear regression analyses, urinary 8-oxodG was positively associated with Cd in both urine (p=0.00067) and breast milk (p=0.0021), and negatively associated with body weight (kg; p=0.0041). Adjustment for age, body weight, socio-economic status, urinary arsenic, as well as magnesium, calcium, and copper in breast milk did not change the association between Cd exposure and urinary 8-oxodG. These findings suggest that early-life low-level exposure to Cd via breast milk induces oxidative stress. Further studies are warranted to elucidate whether this oxidative stress is associated with impaired child health and development.« less

  8. Estimated effects of in utero cocaine exposure on language development through early adolescence.

    PubMed

    Bandstra, Emmalee S; Morrow, Connie E; Accornero, Veronica H; Mansoor, Elana; Xue, Lihua; Anthony, James C

    2011-01-01

    The potential longitudinal effects of prenatal cocaine exposure (PCE) on language functioning were estimated from early childhood through early adolescence in a large, well-retained urban sample of 451 full-term children (242 cocaine-exposed, 209 non-cocaine-exposed) participating in the Miami Prenatal Cocaine Study (MPCS). The sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview, and toxicology assays of maternal and infant urine, and infant meconium. Age-appropriate versions of the Clinical Evaluation of Language Fundamentals (CELF) were used to measure total, expressive, and receptive language at ages 3, 5, and 12years. Longitudinal latent growth curve (LLGC) modeling of the data revealed an association between PCE (measured dichotomously as yes/no) and lower functioning in expressive and total language scores, after considering other sources of variation including child's age at testing, sex, prenatal exposure to alcohol, marijuana, and tobacco, and additional medical and social-demographic covariates. Analyses of level of PCE showed a gradient, i.e. dose-dependent, relationship between PCE level and expressive, receptive, and total language scores in the models controlling for age, child's sex, and other prenatal drug exposures. With additional covariate control these findings were most stable for the total language score. The evidence supports an inference about an enduring stable cocaine-specific effect on children's language abilities, with no effect on language growth over time in the longitudinal trajectory of language development. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Adolescent adrenocortical activity and adiposity: differences by sex and exposure to early maternal depression.

    PubMed

    Ruttle, Paula L; Klein, Marjorie H; Slattery, Marcia J; Kalin, Ned H; Armstrong, Jeffrey M; Essex, Marilyn J

    2014-09-01

    Prior research has linked either basal cortisol levels or stress-induced cortisol responses to adiposity; however, it remains to be determined whether these distinct cortisol measures exert joint or independent effects. Further, it is unclear how they interact with individual and environmental characteristics to predict adiposity. The present study aims to address whether morning cortisol levels and cortisol responses to a psychosocial stressor independently and/or interactively influence body mass index (BMI) in 218 adolescents (117 female) participating in a longitudinal community study, and whether associations are moderated by sex and exposure to early maternal depression. Reports of maternal depressive symptoms were obtained in infancy and preschool. Salivary cortisol measures included a longitudinal morning cortisol measure comprising sampling points across ages 11, 13, 15, and 18 and measures of stress-induced cortisol responses assessed via the Trier Social Stress Test (TSST) at age 18. Lower morning cortisol and higher TSST cortisol reactivity independently predicted higher age 18 BMI. Morning cortisol also interacted with sex and exposure to early maternal depression to predict BMI. Specifically, girls exposed to lower levels of early maternal depression displayed a strong negative morning cortisol-BMI association, and girls exposed to higher levels of maternal depression demonstrated a weaker negative association. Among boys, those exposed to lower levels of maternal depression displayed no association, while those exposed to higher levels of maternal depression displayed a negative morning cortisol-BMI association. Results point to the independent, additive effects of morning and reactive cortisol in the prediction of BMI and suggest that exposure to early maternal depression may exert sexually dimorphic effects on normative cortisol-BMI associations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Anxiety affecting parkinsonian outcome and motor efficiency in adults of an Ohio community with environmental airborne manganese exposure.

    EPA Science Inventory

    Manganese (Mn) is a nutrient and neurotoxicant sometimes associated with mood, motor and neurological effects. Reports of health effects from occupational exposure to Mn are well known, but the reported links to environmental airborne Mn (Mn-Air) are less conclusive. Marietta, OH...

  11. Early histological and functional effects of chronic copper exposure in rat liver.

    PubMed

    Cisternas, Felipe A; Tapia, Gladys; Arredondo, Miguel; Cartier-Ugarte, Denise; Romanque, Pamela; Sierralta, Walter D; Vial, María T; Videla, Luis A; Araya, Magdalena

    2005-10-01

    Cu is an essential trace element capable of producing toxic effects in animals and man when ingested acutely or chronically in excess. Although chronic Cu exposure is increasingly recognized as a public health issue, its early effects remain largely unknown. We approached the significance of a moderate chronic Cu load in young rats to correlate early hepatic histopathological changes with functional alterations of liver cells. For this purpose, supplementation with 1,200 ppm of Cu in rat food for 16 weeks was chosen. In these conditions, Cu load elicited a significant decrease in growth curves. There were mild light microscopy alterations in Cu-treated rats, although increasing intracellular Cu storage was correlated with longer Cu exposure both by histological and biochemical measurements. Ultrastructural alterations included lysosomal inclusions as well as mitochondrial and nuclear changes. Liver perfusion studies revealed higher rates of basal O(2) consumption and colloidal carbon-induced O(2) uptake in Cu-treated rats, with enhanced carbon-induced O(2)/carbon uptake ratios and NF-kappaB DNA binding activity. These changes were time-dependent and returned to control values after 12 or 16 weeks. It is concluded that subchronic Cu loading in young rats induces early hepatic morphological changes, with enhancement in Küpffer cell-dependent respiratory burst activity and NF-kappaB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.

  12. Developmental disruption of medial prefrontal cortical GABAergic function by non-contingent cocaine exposure during early adolescence

    PubMed Central

    Cass, Daryn K.; Thomases, Daniel R.; Caballero, Adriana; Tseng, Kuei Y.

    2013-01-01

    Background Drug experimentation during adolescence is associated with increased risk of drug addiction relative to any other age group. To further our understanding on the neurobiology underlying such liability, we investigate how early adolescent cocaine experience impacts the overall medial prefrontal cortex (mPFC) network function in adulthood. Methods A non-contingent administration paradigm was used to assess the impact of early adolescent cocaine treatment (rats; postnatal days -PD- 35-40) on the overall inhibitory regulation of mPFC activity in adulthood (PD65-75) by means of histochemical and in vivo electrophysiological measures combined with pharmacological manipulations. Results Cocaine exposure during early adolescence yields a distinctive hyper-metabolic PFC state that was not observed in adult (PD75-80)-treated rats. Local field potential recordings expand upon these findings by showing that early adolescent cocaine exposure is associated with an attenuation of mPFC GABAergic inhibition evoked by ventral hippocampal stimulation at beta and gamma frequencies that endures throughout adulthood. Such cocaine-induced mPFC disinhibition was not observed in adult-exposed animals. Furthermore, the normal developmental upregulation of parvalbumin immunoreactivity observed in the mPFC from PD35 to PD65 is lacking following early adolescent cocaine treatment. Conclusion Our data indicate that repeated cocaine exposure during early adolescence can elicit a state of mPFC disinhibition resulting from a functional impairment of the local prefrontal GABAergic network that endures through adulthood. A lack of acquisition of prefrontal GABAergic function during adolescence could trigger long-term deficits in the mPFC that may increase the susceptibility for the onset of substance abuse and related psychiatric disorders. PMID:23558299

  13. Radiation exposure and disease questionnaires of early entrants after the Hiroshima bombing.

    PubMed

    Imanaka, Tetsuji; Endo, Satoru; Kawano, Noriyuki; Tanaka, Kenichi

    2012-03-01

    It is popularly known that people who entered into the ground-zero area shortly after the atomic bombings in Hiroshima and Nagasaki suffered from various syndromes similar to acute radiation effects. External exposures from neutron-induced radionuclides in soil have recently been reassessed based on DS02 calculations as functions of both distance from the hypocentres and elapsed time after the explosions. Significant exposure due to induced radiation can be determined for those who entered the area within 1000 m from the hypocentres shortly after the bombing. Although it was impossible to track the action of each of the survivors over the days or weeks following the bombings in order to make reliable dose estimates for their exposures to soil activation or fallout, four individuals among those early entrants were investigated here to describe useful information of what happened shortly after the bombing.

  14. Neonatal C57BL/6J and parkin mice respond differently following developmental manganese exposure: Result of a high dose pilot study.

    PubMed

    Foster, Melanie L; Bartnikas, Thomas B; Maresca-Fichter, Hailey C; Mercadante, Courtney; Dash, Miriam; Miller, Chelsea; Dorman, David C

    2018-01-01

    It has been suggested that childhood exposure to neurotoxicants may increase the risk of Parkinson's disease (PD) or other neurodegenerative disease in adults. Some recessive forms of PD have been linked to loss-of-function mutations in the Park2 gene that encodes for parkin. The purpose of this pilot study was to evaluate whether responses to neonatal manganese (Mn) exposure differ in mice with a Park2 gene defect (parkin mice) when compared with a wildtype strain (C57BL/6J). Neonatal parkin and C57BL/6J littermates were randomly assigned to 0, 11, or 25mg Mn/kg-day dose groups with oral exposures occurring from postnatal day (PND) 1 through PND 28. Motor activity was measured on PND 19-22 and 29-32. Tissue Mn concentrations were measured in liver, femur, olfactory bulb, frontal cortex, and striatum on PND 29. Hepatic and frontal cortex gene expression of Slc11a2, Slc40a1, Slc30a10, Hamp (liver only), and Park2 were also measured on PND 29. Some strain differences were seen. As expected, decreased hepatic and frontal cortex Park2 expression was seen in the parkin mice when compared with C57BL/6J mice. Untreated parkin mice also had higher liver and femur Mn concentrations when compared with the C57BL/6J mice. Exposure to≥11mg Mn/kg-day was associated with increased brain Mn concentrations in all mice, no strain difference was observed. Manganese exposure in C57Bl6, but not parkin mice, was associated with a negative correlation between striatal Mn concentration and motor activity. Manganese exposure was not associated with changes in frontal cortex gene expression. Decreased hepatic Slc30a10, Slc40a1, and Hamp expression were seen in PND 29 C57BL/6J mice given 25mg Mn/kg-day. In contrast, Mn exposure was only associated with decreased Hamp expression in the parkin mice. Our results suggest that the Parkin gene defect did not increase the susceptibility of neonatal mice to adverse health effects associated with high-dose Mn exposure. Copyright © 2017 Elsevier B

  15. Betel quid chewing as a source of manganese exposure: total daily intake of manganese in a Bangladeshi population.

    PubMed

    Al-Rmalli, Shaban W; Jenkins, Richard O; Haris, Parvez I

    2011-02-07

    A relationship between betel quid chewing in Bangladeshi populations and the development of skin lesions and tremor has been previously reported, for people exposed to high levels of arsenic (As) through drinking contaminated groundwater. Exposure to manganese (Mn) is also known to induce neurotoxicity and levels of Mn in Bangladeshi groundwater are also high. The present study evaluates betel quid chewing as an overlooked source of Mn exposure in a Bangladeshi population. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine (1) urinary Mn levels for 15 chewers and 22 non-chewers from the ethnic Bangladeshi community in the United Kingdom, and (2) Mn levels in betel quids, its individual components and other Bangladeshi foods. Betel quid chewers displayed a significantly higher (P = 0.009) mean Mn concentration in urine (1.93 μg L(-1)) compared to non-chewers (0.62 μg L(-1)). High levels of Mn were detected in Piper betel leaves with an overall average of 135 mg kg(-1) (range 26 -518 mg kg(-1)). The mean concentration of Mn in betel quid was 41 mg kg(-1) (SD 27) and the daily intake of Mn in the Bangladeshi population was estimated to be 20.3 mg/day. Chewing six betel quids could contribute up to 18% of the maximum recommended daily intake of Mn. We have demonstrated that Mn in betel quids is an overlooked source of exposure to Mn in humans. Chewers display a 3.1 fold increased urinary Mn concentration compared to non-chewers. The practice of betel quid chewing contributes a high proportion of the maximum recommended daily intake of Mn, which could make chewers in Bangladesh more vulnerable to Mn neurotoxicity.

  16. Betel quid chewing as a source of manganese exposure: total daily intake of manganese in a Bangladeshi population

    PubMed Central

    2011-01-01

    Background A relationship between betel quid chewing in Bangladeshi populations and the development of skin lesions and tremor has been previously reported, for people exposed to high levels of arsenic (As) through drinking contaminated groundwater. Exposure to manganese (Mn) is also known to induce neurotoxicity and levels of Mn in Bangladeshi groundwater are also high. The present study evaluates betel quid chewing as an overlooked source of Mn exposure in a Bangladeshi population. Methods Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine (1) urinary Mn levels for 15 chewers and 22 non-chewers from the ethnic Bangladeshi community in the United Kingdom, and (2) Mn levels in betel quids, its individual components and other Bangladeshi foods. Results Betel quid chewers displayed a significantly higher (P = 0.009) mean Mn concentration in urine (1.93 μg L-1) compared to non-chewers (0.62 μg L-1). High levels of Mn were detected in Piper betel leaves with an overall average of 135 mg kg-1 (range 26 -518 mg kg-1). The mean concentration of Mn in betel quid was 41 mg kg-1 (SD 27) and the daily intake of Mn in the Bangladeshi population was estimated to be 20.3 mg/day. Chewing six betel quids could contribute up to 18% of the maximum recommended daily intake of Mn. Conclusion We have demonstrated that Mn in betel quids is an overlooked source of exposure to Mn in humans. Chewers display a 3.1 fold increased urinary Mn concentration compared to non-chewers. The practice of betel quid chewing contributes a high proportion of the maximum recommended daily intake of Mn, which could make chewers in Bangladesh more vulnerable to Mn neurotoxicity. PMID:21299859

  17. Chronic exposure to bisphenol a impairs progesterone receptor-mediated signaling in the uterus during early pregnancy

    PubMed Central

    Li, Quanxi; Davila, Juanmahel; Bagchi, Milan K.; Bagchi, Indrani C.

    2016-01-01

    Environmental and occupational exposure to endocrine disrupting chemicals (EDCs) is a major threat to female reproductive health. Bisphenol A (BPA), an environmental toxicant that is commonly found in polycarbonate plastics and epoxy resins, has received much attention due to its estrogenic activity and high risk of chronic exposure in human. Whereas BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In a recent publication in Endocrinology, we demonstrated that prolonged exposure to an environmental relevant dose of BPA disrupts progesterone receptor-regulated uterine functions, thus affecting uterine receptivity for embryo implantation and decidua morphogenesis, two critical events for establishment and maintenance of early pregnancy. In particular we reported a marked impairment of progesterone receptor (PGR) expression and its downstream effector HAND2 in the uterine stromal cells in response to chronic BPA exposure. In an earlier study we have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor (FGF) expression and the MAP kinase signaling pathway, thus inhibiting epithelial proliferation. Interestingly we observed that downregulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with an enhanced activation of FGFR and MAPK signaling, aberrant proliferation, and lack of uterine receptivity in the epithelium. In addition, the proliferation and differentiation of endometrial stromal cells to decidual cells, an event critical for the maintenance of early pregnancy, was severely compromised in response to BPA. This research highlight will provide an overview of our findings and discuss the potential mechanisms by which chronic BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy. PMID:28239613

  18. Media ideals and early adolescents' body image: Selective avoidance or selective exposure?

    PubMed

    Rousseau, Ann; Eggermont, Steven

    2018-06-05

    The present study combines selective exposure theory with body image coping literature to study effects of media internalization in early adolescence. The main objective was to explore how early adolescents selectively internalize media body ideals to manage their body image. To examine the role of media internalization in early adolescents' body image management, we used two-wave panel data (N Wave1  = 1986) gathered among 9- to 14-year-olds. Structural equation analyses indicated that media internalization (Wave 1) positively related to body surveillance (Wave 2). Body surveillance (Wave 2), in turn, was associated with more body image self-discrepancy (Wave 2). In addition, body image self-discrepancy (Wave 1) related to higher body surveillance (Wave 1). Body surveillance, in turn, related to more media internalization cross-sectionally, but less media internalization six months later. Taken together, these results suggest a role for media internalization in early adolescents' body image management. Theoretical and practical implications are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Environmental manganese exposure and associations with memory, executive functions, and hyperactivity in Brazilian children.

    PubMed

    Carvalho, Chrissie Ferreira de; Oulhote, Youssef; Martorelli, Marina; Carvalho, Carla Oliveira de; Menezes-Filho, José Antônio; Argollo, Nayara; Abreu, Neander

    2018-02-09

    Manganese (Mn) is an essential element, however high levels of Mn have been associated with lower neuropsychological performance and behavioral problems in children. We investigated the associations between hair Mn concentrations and neuropsychological and behavioral performances among children with long-term exposure to airborne Mn aged between 7 and 12 years. Neuropsychological performance included tests of: verbal memory, inhibitory control, cognitive flexibility, verbal fluency, and motor function. We used the Conners Abbreviated Rating Scale for teachers to assess students' behaviors of hyperactivity. Hair manganese (MnH) concentrations in children and exposure to airborne manganese from a ferro-manganese alloy plant were analyzed and correlated with tests scores. Multivariable linear models adjusting for potential confounders showed that elevated levels of MnH were associated with lower performance in verbal memory, as measured by the free recall after interference (β = - 1.8; 95% CI: - 3.4, - 0.2), which indicates susceptibility to interference, and Delayed Effect (β = -2.0; 95% CI: -3.7, - 0.2), representing a loss of information over time. Additionally, we found patterns of effect modification by sex in three subtests measuring verbal memory: the free recall after interference score, Interference Effect, and Delayed Effect (all at p < 0.10). Overall, the results suggest that long-term airborne Mn exposure may be associated with lower performance in verbal memory, and hyperactivity behaviors. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Mn-Site Doped CaMnO 3: Creation of the CMR Effect

    NASA Astrophysics Data System (ADS)

    Raveau, B.; Zhao, Y. M.; Martin, C.; Hervieu, M.; Maignan, A.

    2000-01-01

    The doping of CaMnO3-δ at Mn sites with pentavalent and hexavalent d0 elements - Nb, Ta, W, Mo - modifies the resistivity behavior of this phase, extending the insulating domain and increasing significantly the resistivity at low temperature as the doping element content increases. The higher valency of the doping element introduces electrons; i.e., Mn3+ species are formed in the Mn4+ matrix. Double exchange phenomena then allow ferromagnetic interactions, by application of external magnetic fields which are similar to those observed for electron-doped manganites Ca1-xLnxMnO3 (x≤0.15), but with smaller magnetic moments. Consequently, this Mn site doping induces CMR properties with resistivity ratios considerably larger than those for CaMnO3-δ.

  1. Evaluating cardiac risk: exposure response analysis in early clinical drug development.

    PubMed

    Grenier, Julie; Paglialunga, Sabina; Morimoto, Bruce H; Lester, Robert M

    2018-01-01

    The assessment of a drug's cardiac liability has undergone considerable metamorphosis by regulators since International Council for Harmonization of Technical Requirement for Pharmaceuticals for Human Use E14 guideline was introduced in 2005. Drug developers now have a choice in how proarrhythmia risk can be evaluated; the options include a dedicated thorough QT (TQT) study or exposure response (ER) modeling of intensive electrocardiogram (ECG) captured in early clinical development. The alternative approach of ER modeling was incorporated into a guidance document in 2015 as a primary analysis tool which could be utilized in early phase dose escalation studies as an option to perform a dedicated TQT trial. This review will describe the current state of ER modeling of intensive ECG data collected during early clinical drug development; the requirements with regard to the use of a positive control; and address the challenges and opportunities of this alternative approach to assessing QT liability.

  2. Evaluation of the effect of an environmental management program on exposure to manganese in a mining zone in Mexico.

    PubMed

    Cortez-Lugo, Marlene; Riojas-Rodríguez, Horacio; Moreno-Macías, Hortensia; Montes, Sergio; Rodríguez-Agudelo, Yaneth; Hernández-Bonilla, David; Catalán-Vázquez, Minerva; Díaz-Godoy, Raúl; Rodríguez-Dozal, Sandra

    2018-01-01

    In the state of Hidalgo, Mexico, is found the largest second deposit of Manganese (Mn) in Latin America. Various studies on the sources of emission, exposure, and the effects on the health of children and adults have been conducted utilizing an ecosystem approach. Given the findings of Mn levels in air and the neurocognitive effects, an Environmental Management Program (EMP) was designed and implemented with the purpose of reducing exposure to Mn of the population, including various actions for reducing Mn emissions into the atmosphere. To evaluate the impact of the EMP on the concentrations of Mn in air, as well as the modification of exposure to Mn in the blood and hair of adult residents of the communities intervened. A quasi-experimental study was conducted in five rural communities, in which Mn concentrations were evaluated in air and in blood in the years 2002 and 2007, pre-intervention, and in 2013, postintervention. In 2003, the concentration of hair Mn among the communities was evaluated. Measurements were carried out of Particulate Matter (PM) of >10 and 2.5μm (PM10 and PM2.5), and Mn in PM10 and PM2.5 were measured using proton-induced X-ray emissions (PIXE). The method of Difference in Differences (DID) was applied to estimate the impact of EMP on Mn concentrations in particulate matter via linear regression through multilevel models. To evaluate the effect of Mn concentrations in air over Mn concentrations in blood in both study periods in the mining communities per year (2002 and 2013), a linear regression model for each year was employed. We estimated that the EMP contributed to reducing the average daily concentrations of Mn in PM10 and PM2.5 by 92 and 85%, respectively. The adjusted model did not show an effect of Mn concentrations in air over Mn concentrations in blood in both study periods. The results suggest that the measures implemented to reduce Mn emissions in air exerted a significant impact on the reduction of inhaled exposure in adult

  3. Editor’s Highlight: Lower Fractional Anisotropy in the Globus Pallidus of Asymptomatic Welders, a Marker for Long-Term Welding Exposure

    PubMed Central

    Lee, Eun-Young; Flynn, Michael R.; Du, Guangwei; Lewis, Mechelle M.; Herring, Amy H.; Van Buren, Eric; Van Buren, Scott; Kong, Lan; Mailman, Richard B.; Huang, Xuemei

    2016-01-01

    Introduction: Welding fumes contain several metals including manganese (Mn), iron (Fe), and copper (Cu) that at high exposure may co-influence welding-related neurotoxicity. The relationship between brain accumulation of these metals and neuropathology, especially in welders with subclinical exposure levels, is unclear. This study examined the microstructural integrity of basal ganglia (BG) regions in asymptomatic welders using diffusion tensor imaging (DTI). Methods: Subjects with (n = 43) and without (age- and gender-matched controls; n = 31) history of welding were studied. Occupational questionnaires estimated short-term (HrsW; welding hours and E90; cumulative exposure, past 90 days) and long-term (YrsW; total years welding and ELT; cumulative exposure, lifetime) exposure. Whole blood metal levels (Mn, Fe, and Cu) were obtained. Brain MRI pallidal index (PI), R1 (1/T1), and R2* (1/T2*) were measured to estimate Mn and Fe accumulation in BG [caudate, putamen, and globus pallidus (GP)]. DTI was used to assess BG microstructural differences, and related with exposure measurements. Results: When compared with controls, welders had significantly lower fractional anisotropy (FA) in the GP. In welders, GP FA values showed non-linear relationships to YrsW, blood Mn, and PI. GP FA decreased after a critical level of YrsW or Mn was reached, whereas it decreased with increasing PI values until plateauing at the highest PI values. GP FA, however, did not show any relationship with short-term exposure measurements (HrsW, E90), blood Cu and Fe, or R2* values. Conclusion: GP FA captured microstructural changes associated with chronic low-level Mn exposure, and may serve as a biomarker for neurotoxicity in asymptomatic welders. PMID:27466214

  4. Affinity for risky behaviors following prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study.

    PubMed

    Aschengrau, Ann; Weinberg, Janice M; Janulewicz, Patricia A; Romano, Megan E; Gallagher, Lisa G; Winter, Michael R; Martin, Brett R; Vieira, Veronica M; Webster, Thomas F; White, Roberta F; Ozonoff, David M

    2011-12-02

    Many studies of adults with acute and chronic solvent exposure have shown adverse effects on cognition, behavior and mood. No prior study has investigated the long-term impact of prenatal and early childhood exposure to the solvent tetrachloroethylene (PCE) on the affinity for risky behaviors, defined as smoking, drinking or drug use as a teen or adult. This retrospective cohort study examined whether early life exposure to PCE-contaminated drinking water influenced the occurrence of cigarette smoking, alcohol consumption, and drug use among adults from Cape Cod, Massachusetts. Eight hundred and thirty-one subjects with prenatal and early childhood PCE exposure and 547 unexposed subjects were studied. Participants completed questionnaires to gather information on risky behaviors as a teenager and young adult, demographic characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure was estimated using the U.S. EPA's water distribution system modeling software (EPANET) that was modified to incorporate a leaching and transport model to estimate PCE exposures from pipe linings. Individuals who were highly exposed to PCE-contaminated drinking water during gestation and early childhood experienced 50-60% increases in the risk of using two or more major illicit drugs as a teenager or as an adult (Relative Risk (RR) for teen use = 1.6, 95% CI: 1.2-2.2; and RR for adult use = 1.5, 95% CI: 1.2-1.9). Specific drugs for which increased risks were observed included crack/cocaine, psychedelics/hallucinogens, club/designer drugs, Ritalin without a prescription, and heroin (RRs:1.4-2.1). Thirty to 60% increases in the risk of certain smoking and drinking behaviors were also seen among highly exposed subjects. The results of this study suggest that risky behaviors, particularly drug use, are more frequent among adults with high PCE exposure levels during gestation and early childhood. These findings should be confirmed in follow

  5. Affinity for risky behaviors following prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study

    PubMed Central

    2011-01-01

    Background Many studies of adults with acute and chronic solvent exposure have shown adverse effects on cognition, behavior and mood. No prior study has investigated the long-term impact of prenatal and early childhood exposure to the solvent tetrachloroethylene (PCE) on the affinity for risky behaviors, defined as smoking, drinking or drug use as a teen or adult. Objectives This retrospective cohort study examined whether early life exposure to PCE-contaminated drinking water influenced the occurrence of cigarette smoking, alcohol consumption, and drug use among adults from Cape Cod, Massachusetts. Methods Eight hundred and thirty-one subjects with prenatal and early childhood PCE exposure and 547 unexposed subjects were studied. Participants completed questionnaires to gather information on risky behaviors as a teenager and young adult, demographic characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure was estimated using the U.S. EPA's water distribution system modeling software (EPANET) that was modified to incorporate a leaching and transport model to estimate PCE exposures from pipe linings. Results Individuals who were highly exposed to PCE-contaminated drinking water during gestation and early childhood experienced 50-60% increases in the risk of using two or more major illicit drugs as a teenager or as an adult (Relative Risk (RR) for teen use = 1.6, 95% CI: 1.2-2.2; and RR for adult use = 1.5, 95% CI: 1.2-1.9). Specific drugs for which increased risks were observed included crack/cocaine, psychedelics/hallucinogens, club/designer drugs, Ritalin without a prescription, and heroin (RRs:1.4-2.1). Thirty to 60% increases in the risk of certain smoking and drinking behaviors were also seen among highly exposed subjects. Conclusions The results of this study suggest that risky behaviors, particularly drug use, are more frequent among adults with high PCE exposure levels during gestation and early childhood

  6. Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Sunagawa, Mayumi; Mangala, Lingegowda; Zhang, Ye; Kahdim, Munira; Wilson, Bobby; Cucinotta, Francis A.; Wu, Honglu

    2011-01-01

    Tumor formation in humans or animals is a multi-step process. An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

  7. [Influence of early childhood stress exposure and traumatic life events on pain perception].

    PubMed

    Tesarz, J; Gerhardt, A; Eich, W

    2018-06-05

    Adult pain perception is influenced substantially by interactions between mind, body, and social environment during early life. Early stress exposure and traumatic life events induce powerful psychophysical stress reactions that exert multiple neurofunctional processes. This has significant implications for pain perception and pain processing. As part of this review, the complex relationships between traumatic stress experiences and associated psychobiological mechanisms of chronic pain will be discussed. Based on selected studies, psychophysiological findings are presented and possible underlying mechanisms are discussed. The article concludes with a discussion of potential implications for treatment.

  8. Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

    PubMed

    Morales, Eva; Garcia-Esteban, Raquel; de la Cruz, Oscar Asensio; Basterrechea, Mikel; Lertxundi, Aitana; de Dicastillo, Maria D Martinez López; Zabaleta, Carlos; Sunyer, Jordi

    2015-01-01

    Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed. Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. In utero and early childhood exposure to arsenic decreases lung function in children.

    PubMed

    Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R Clark; Gandolfi, A Jay; Gonzalez-De Alba, Cesar

    2015-04-01

    The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⁻¹. The mean urinary As level registered in the studied subjects was 141.2 µg l⁻¹ and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Microbially-induced Fe and Mn oxides in condensed pelagic sediments (Middle-Upper Jurassic, Western Sicily)

    NASA Astrophysics Data System (ADS)

    Préat, A.; Mamet, B.; Di Stefano, P.; Martire, L.; Kolo, K.

    2011-06-01

    This article presents a petrographic comparison of the Rosso Ammonitico facies of Western Sicily and the original Rosso Ammonitico Veronese of Northern Italy based on a total of 27 sections. The Rosso Ammonitico has been the subject of numerous controversies that range from bathyal to shallow-water platform sedimentation. Therefore it seemed interesting to verify if the term Rosso Ammonitico has the same geologic connotation from region to region. The Middle-Upper Jurassic Rosso Ammonitico of Western Sicily is a condensed succession formed during a period of extensional synsedimentary tectonics related to the spreading of the Ionian Ocean. Slope-to-basin or pelagic carbonate deposits characterize the sedimentation which consists of reddish mudstones and wackestones. The abundant fauna is composed of radiolarians, protoglobigerinids, Saccocoma, Bositra associated with ammonites. A few ferruginous hardgrounds, Fe-Mn oxide crusts and Mn-coated condensation horizons are also present. The red matrices contain abundant Fe-Mn encrusted, microbored and bioeroded bioclasts. Sporadic Fe-Mn oncolites composed of amorphous Mn-minerals and goethite are also conspicuous. The matrix, as well as the shells and the fillings of the complex associated veinlets, are frequently altered into calcite microsparite. Submicronic iron bacterial and fungal filaments associated with mineralized extracellular polymeric substances (EPS) are observed in the matrix. They record dysaerobic microenvironments at or near the sediment-water interfaces. Early mineralized discontinuities enhanced by subsequent pressure dissolution are reported in the succession. Mn-(Ni) bacterial filaments are exceptionally observed in the cortex of the Fe-Mn oncolites. As a consequence of an early lithification, the Mn filaments are poorly preserved. The pigmentation of the rock is due to the dispersion of submicronic oxyhydroxides (now goethite and amorphous iron) formed by bacterial mediation during early diagenesis

  11. Editor's Highlight: Lower Fractional Anisotropy in the Globus Pallidus of Asymptomatic Welders, a Marker for Long-Term Welding Exposure.

    PubMed

    Lee, Eun-Young; Flynn, Michael R; Du, Guangwei; Lewis, Mechelle M; Herring, Amy H; Van Buren, Eric; Van Buren, Scott; Kong, Lan; Mailman, Richard B; Huang, Xuemei

    2016-09-01

    Welding fumes contain several metals including manganese (Mn), iron (Fe), and copper (Cu) that at high exposure may co-influence welding-related neurotoxicity. The relationship between brain accumulation of these metals and neuropathology, especially in welders with subclinical exposure levels, is unclear. This study examined the microstructural integrity of basal ganglia (BG) regions in asymptomatic welders using diffusion tensor imaging (DTI). Subjects with (n = 43) and without (age- and gender-matched controls; n = 31) history of welding were studied. Occupational questionnaires estimated short-term (HrsW; welding hours and E90; cumulative exposure, past 90 days) and long-term (YrsW; total years welding and ELT; cumulative exposure, lifetime) exposure. Whole blood metal levels (Mn, Fe, and Cu) were obtained. Brain MRI pallidal index (PI), R1 (1/T1), and R2* (1/T2*) were measured to estimate Mn and Fe accumulation in BG [caudate, putamen, and globus pallidus (GP)]. DTI was used to assess BG microstructural differences, and related with exposure measurements. When compared with controls, welders had significantly lower fractional anisotropy (FA) in the GP. In welders, GP FA values showed non-linear relationships to YrsW, blood Mn, and PI. GP FA decreased after a critical level of YrsW or Mn was reached, whereas it decreased with increasing PI values until plateauing at the highest PI values. GP FA, however, did not show any relationship with short-term exposure measurements (HrsW, E90), blood Cu and Fe, or R(2)* values. GP FA captured microstructural changes associated with chronic low-level Mn exposure, and may serve as a biomarker for neurotoxicity in asymptomatic welders. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Manganese Fractionation Using a Sequential Extraction Method to Evaluate Welders' Shielded Metal Arc Welding Exposures During Construction Projects in Oil Refineries.

    PubMed

    Hanley, Kevin W; Andrews, Ronnee; Bertke, Steven; Ashley, Kevin

    2015-01-01

    The National Institute for Occupational Safety and Health has conducted an occupational exposure assessment study of manganese (Mn) in welding fume of construction workers rebuilding tanks, piping, and process equipment at two oil refineries. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. Seventy-two worker-days were monitored for either total or respirable Mn during stick welding and associated activities both within and outside of confined spaces. The samples were analyzed using an experimental method to separate different Mn fractions by valence states based on selective chemical solubility. The full-shift total particulate Mn time-weighted average (TWA) breathing zone concentrations ranged from 0.013-29 for soluble Mn in a mild ammonium acetate solution; from 0.26-250 for Mn(0,2+) in acetic acid; from non-detectable (ND) - 350 for Mn(3+,4+) in hydroxylamine-hydrochloride; and from ND - 39 micrograms per cubic meter (μg/m(3)) for insoluble Mn fractions in hydrochloric and nitric acid. The summation of all Mn fractions in total particulate TWA ranged from 0.52-470 μg/m(3). The range of respirable particulate Mn TWA concentrations were from 0.20-28 for soluble Mn; from 1.4-270 for Mn(0,2+); from 0.49-150 for Mn(3+,4+); from ND - 100 for insoluble Mn; and from 2.0-490 μg/m(3) for Mn (sum of fractions). For all jobs combined, total particulate TWA GM concentrations of the Mn(sum) were 99 (GSD = 3.35) and 8.7 (GSD = 3.54) μg/m(3) for workers inside and outside of confined spaces; respirable Mn also showed much higher levels for welders within confined spaces. Regardless of particle size and confined space work status, Mn(0,2+) fraction was the most abundant followed by Mn(3+,4+) fraction, typically >50% and ∼30-40% of Mn(sum), respectively. Eighteen welders' exposures exceeded the ACGIH Threshold Limit Values for total Mn (100 μg/m(3)) and 25 exceeded the recently adopted respirable

  13. Manganese fractionation using a sequential extraction method to evaluate welders’ shielded metal arc welding exposures during construction projects in oil refineries

    PubMed Central

    Hanley, Kevin W.; Andrews, Ronnee; Bertke, Steven; Ashley, Kevin

    2015-01-01

    The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in welding fume of construction workers rebuilding tanks, piping, and process equipment at two oil refineries. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. Seventy-two worker-days were monitored for either total or respirable Mn during stick welding and associated activities both within and outside of confined spaces. The samples were analyzed using an experimental method to separate different Mn fractions by valence states based on selective chemical solubility. The full-shift total particulate Mn time-weighted average (TWA) breathing zone concentrations ranged from 0.013 – 29 for soluble Mn in a mild ammonium acetate solution; from 0.26 – 250 for Mn0,2+ in acetic acid; from non-detectable (ND) – 350 for Mn3+,4+ in hydroxylamine-hydrochloride; and from ND – 39 micrograms per cubic meter (μg/m3) for insoluble Mn fractions in hydrochloric and nitric acid. The summation of all Mn fractions in total particulate TWA ranged from 0.52 to 470 μg/m3. The range of respirable particulate Mn TWA concentrations were from 0.20 – 28 for soluble Mn; from 1.4 – 270 for Mn0,2+; from 0.49 – 150 for Mn3+,4+; from ND – 100 for insoluble Mn; and from 2.0 – 490 μg/m3 for Mn (sum of fractions). For all jobs combined, total particulate TWA GM concentrations of the Mn(sum) were 99 (GSD=3.35) and 8.7 (GSD=3.54) μg/m3 for workers inside and outside of confined spaces; respirable Mn also showed much higher levels for welders within confined spaces. Regardless of particle size and confined space work status, Mn0,2+ fraction was the most abundant followed by Mn3+,4+ fraction, typically >50% and ~30-40% of Mn(sum), respectively. Eighteen welders’ exposures exceeded the ACGIH Threshold Limit Values for total Mn (100 μg/m3) and 25 exceeded the recently adopted

  14. Prenatal Cocaine Disrupts Serotonin Signaling-Dependent Behaviors: Implications for Sex Differences, Early Stress and Prenatal SSRI Exposure

    PubMed Central

    Williams, Sarah K; Lauder, Jean M; Johns, Josephine M

    2011-01-01

    Prenatal cocaine (PC) exposure negatively impacts the developing nervous system, including numerous changes in serotonergic signaling. Cocaine, a competitive antagonist of the serotonin transporter, similar to selective serotonin reuptake inhibitors (SSRIs), also blocks dopamine and norepinephrine transporters, leaving the direct mechanism through which cocaine disrupts the developing serotonin system unclear. In order to understand the role of the serotonin transporter in cocaine’s effect on the serotonergic system, we compare reports concerning PC and prenatal antidepressant exposure and conclude that PC exposure affects many facets of serotonergic signaling (serotonin levels, receptors, transporters) and that these effects differ significantly from what is observed following prenatal SSRI exposure. Alterations in serotonergic signaling are dependent on timing of exposure, test regimens, and sex. Following PC exposure, behavioral disturbances are observed in attention, emotional behavior and stress response, aggression, social behavior, communication, and like changes in serotonergic signaling, these effects depend on sex, age and developmental exposure. Vulnerability to the effects of PC exposure can be mediated by several factors, including allelic variance in serotonergic signaling genes, being male (although fewer studies have investigated female offspring), and experiencing the adverse early environments that are commonly coincident with maternal drug use. Early environmental stress results in disruptions in serotonergic signaling analogous to those observed with PC exposure and these may interact to produce greater behavioral effects observed in children of drug-abusing mothers. We conclude that based on past evidence, future studies should put a greater emphasis on including females and monitoring environmental factors when studying the impact of PC exposure. PMID:22379462

  15. Dyslipdemia induced by chronic low dose co-exposure to lead, cadmium and manganese in rats: the role of oxidative stress.

    PubMed

    Oladipo, Olusola Olalekan; Ayo, Joseph Olusegun; Ambali, Suleiman Folorunsho; Mohammed, Bisalla; Aluwong, Tanang

    2017-07-01

    Lead (Pb), cadmium (Cd) and manganese (Mn) have many potential adverse health effects in vitro and in animal models of clinical toxicity. The current study investigated the dyslipidaemic and oxidative stress effects of chronic low-dose oral exposure to Pb, Cd and Mn and the combination (Pb+Cd+Mn) in rats for 15 weeks. Chronic exposure to the metals did not significantly (P>0.05) alter serum lipid profiles. However, the atherogenic index decreased by 32.2% in the Pb+Cd+Mn group, relative to the control. The triglyceride/high-density lipoprotein cholesterol ratio decreased by 39.4% in the Pb+Cd+Mn group, relative to the control, and elevated by 81.8, 94.8 and 20.8%, relative to the Pb, Cd and Mn groups, respectively. While the serum concentrations of malondialdehyde significantly increased in the Mn and Pb+Cd+Mn groups, that of glutathione peroxidase-1 decreased in the Pb+Cd+Mn group, and metallothionein-1 and zinc concentrations markedly decreased in all the metal treatment groups. The results suggest that long-term exposure of rats to Pb+Cd+Mn may result in hypolipidaemia, mediated via oxidative stress and metal interactions. Individuals who are constantly exposed to environmentally relevant levels of the metals may be at risk of hypolipidaemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Tempering of Mn and Mn-Si-V dual-phase steels

    NASA Astrophysics Data System (ADS)

    Speich, G. R.; Schwoeble, A. J.; Huffman, G. P.

    1983-06-01

    Changes in the yield behavior, strength, and ductility of a Mn and a Mn-Si-V d11Al-phase (ferrite-martensite) steel were investigated after tempering one hour at 200 to 600 °C. The change in yield behavior was complex in both steels with the yield strength first increasing and then decreasing as the tempering temperature was increased. This complex behavior is attributed to a combination of factors including carbon segregation to dislocations, a return of discontinuous yielding, and the relief of resid11Al stresses. In contrast, the tensile strength decreased continuously as the tempering temperature was increased in a manner that could be predicted from the change in hardness of the martensite phase using a simple composite strengthening model. The initial tensile ductility (total elongation) of the Mn-Si-V steel was much greater than that of the Mn steel. However, upon tempering up to 400 °C, the ductility of the Mn-Si-V decreased whereas that of the Mn steel increased. As a result, both steels had similar ductilities after tempering at 400 °C or higher temperatures. These results are attributed to the larger amounts of retained austenite in the Mn-Si-V steel (9 pct) compared to the Mn steel (3 pct) and its contribution to tensile ductility by transforming to martensite during plastic straining. Upon tempering at 400 °C, the retained austenite decomposes to bainite and its contribution to tensile ductility is eliminated.

  17. Dietary cyanogen exposure and early child neurodevelopment: An observational study from the Democratic Republic of Congo.

    PubMed

    Kashala-Abotnes, Espérance; Sombo, Marie-Thérèse; Okitundu, Daniel L; Kunyu, Marcel; Bumoko Makila-Mabe, Guy; Tylleskär, Thorkild; Sikorskii, Alla; Banea, Jean-Pierre; Mumba Ngoyi, Dieudonné; Tshala-Katumbay, Désiré; Boivin, Michael J

    2018-01-01

    Dietary cyanogen exposure from ingesting bitter (toxic) cassava as a main source of food in sub-Saharan Africa is related to neurological impairments in sub-Saharan Africa. We explored possible association with early child neurodevelopmental outcomes. We undertook a cross-sectional neurodevelopmental assessment of 12-48 month-old children using the Mullen Scale of Early Learning (MSEL) and the Gensini Gavito Scale (GGS). We used the Hopkins Symptoms Checklist-10 (HSCL-10) and Goldberg Depression Anxiety Scale (GDAS) to screen for symptoms of maternal depression-anxiety. We used the cyanogen content in household cassava flour and urinary thiocyanate (SCN) as biomarkers of dietary cyanogen exposure. We employed multivariable generalized linear models (GLM) with Gamma link function to determine predictors of early child neurodevelopmental outcomes. The mean (SD) and median (IQR) of cyanogen content of cassava household flour were above the WHO cut-off points of 10 ppm (52.18 [32·79]) and 50 (30-50) ppm, respectively. Mean (SD) urinary levels of thiocyanate and median (IQR) were respectively 817·81 (474·59) and 688 (344-1032) μmole/l in mothers, and 617·49 (449·48) and 688 (344-688) μmole/l in children reflecting individual high levels as well as a community-wide cyanogenic exposure. The concentration of cyanide in cassava flour was significantly associated with early child neurodevelopment, motor development and cognitive ability as indicated by univariable linear regression (p < 0.05). After adjusting for biological and socioeconomic predictors at multivariable analyses, fine motor proficiency and child neurodevelopment remained the main predictors associated with the concentration of cyanide in cassava flour: coefficients of -0·08 to -.15 (p < 0·01). We also found a significant association between child linear growth, early child neurodevelopment, cognitive ability and motor development at both univariable and multivariable linear regression analyses

  18. The Information Book Flood: Is Additional Exposure Enough to Support Early Literacy Development?

    ERIC Educational Resources Information Center

    Neuman, Susan B.

    2017-01-01

    The purpose of this quasi-experimental study was to examine the influence of a book distribution program targeted at enhancing children's exposure to information books. The research examined whether a flood of information books in early childhood settings, placing libraries in a central role, could affect growth in language, content-related…

  19. Persistent behavioral effects following early life exposure to retinoic acid or valproic acid in zebrafish

    PubMed Central

    Bailey, Jordan M.; Oliveri, Anthony N.; Karbhari, Nishika; Brooks, Roy A.J.; De La Rocha, Amberlene J.; Janardhan, Sheila; Levin, Edward D.

    2015-01-01

    BACKGROUND Moderate to severe dysregulation in retinoid signaling during early development is associated with a constellation of physical malformations and/or neural tube defects, including spina bifida. It is thought that more subtle dysregulation of this system, which might be achievable via dietary (i.e. hypervitaminosis A) or pharmacological (i.e. valproic acid) exposure in humans, will manifest on behavioral domains including sociability, without overt physical abnormalities. METHODS During early life, zebrafish were exposed to low doses of two chemicals that disrupt retinoid signaling. From 0-5 dpf, larvae were reared in aqueous solutions containing retinoic acid (0, 0.02, 0.2 or 2 nM) or valproic acid (0, 0.5, 5.0 or 50 uM). One cohort of zebrafish was assessed using a locomotor activity screen at 6-dpf; another was reared to adulthood and assessed using a neurobehavioral test battery (startle habituation, novel tank exploration, shoaling, and predator escape/avoidance). RESULTS There was no significant increase in the incidence of physical malformation among exposed fish compared to controls. Both retinoic acid and valproic acid exposures during development disrupted larval activity with persisting behavioral alterations later in life, primarily manifesting as decreased social affiliation. CONCLUSIONS Social behavior and some aspects of motor function were altered in exposed fish; the importance of examining emotional or psychological consequences of early life exposure to retinoid acting chemicals is discussed. PMID:26439099

  20. Exposure to the Chinese famine in early life and the risk of anaemia in adulthood.

    PubMed

    Shi, Zumin; Zhang, Cuilin; Zhou, Minghao; Zhen, Shiqi; Taylor, Anne W

    2013-10-01

    Famine exposure during the early stage of life is related to a number of adulthood diseases. The objective of this study was to examine the association of early life exposure to the famine in China (1959-1961) with the risk of anaemia in adulthood. We used the data of 2007 adults born between 1954 and 1964 in Jiangsu province from the 2002 Chinese National Nutrition and Health Survey. Anaemia was defined as haemoglobin concentration <12 g/dl in women and <13 g/dl in men. Prevalence of anaemia in adulthood in nonexposed, fetal-exposed, early-childhood, mid-childhood, and late-childhood exposed to famine groups were 26.0%, 33.8%, 28.1%, 28.2% and 29.7%, respectively. Overall, fetal-exposed to famine was associated with 37% increased risk of anaemia as compared with those non-exposed after adjusting for income, education, place of residence, smoking, alcohol drinking, job, hypertension and BMI; relative risk (95% confidence interval) (RR (95% CI)) was 1.37 (1.09, 1.71). In general, this association appeared to be stronger among men, those who were currently overweight or obese, or those of lower educational levels. Corresponding RR (95% CI) was 1.87 (1.21-2.87), 1.75 (1.20-2.56), and 2.07 (1.37-3.12), respectively. Fetal exposure to the Chinese famine was associated with an increased risk of anaemia in adulthood.

  1. Early Exposure to Dogs and Farm Animals and the Risk of Childhood Asthma.

    PubMed

    Fall, Tove; Lundholm, Cecilia; Örtqvist, Anne K; Fall, Katja; Fang, Fang; Hedhammar, Åke; Kämpe, Olle; Ingelsson, Erik; Almqvist, Catarina

    2015-11-01

    The association between early exposure to animals and childhood asthma is not clear, and previous studies have yielded contradictory results. To determine whether exposure to dogs and farm animals confers a risk of asthma. In a nationwide cohort study, the association between early exposure to dogs and farm animals and the risk of asthma was evaluated and included all children born in Sweden from January 1, 2001, to December 31, 2010 (N = 1,011,051), using registry data on dog and farm registration, asthma medication, diagnosis, and confounders for parents and their children. The association was assessed as the odds ratio (OR) for a current diagnosis of asthma at age 6 years for school-aged children and as the hazard ratio (HR) for incident asthma at ages 1 to 5 years for preschool-aged children. Data were analyzed from January 1, 2007, to September 30, 2012. Living with a dog or farm animal. Childhood asthma diagnosis and medication used. Of the 1,011,051 children born during the study period, 376,638 preschool-aged (53,460 [14.2%] exposed to dogs and 1729 [0.5%] exposed to farm animals) and 276,298 school-aged children (22,629 [8.2%] exposed to dogs and 958 [0.3%] exposed to farm animals) were included in the analyses. Of these, 18,799 children (5.0%) in the preschool-aged children's cohort experienced an asthmatic event before baseline, and 28,511 cases of asthma and 906,071 years at risk were recorded during follow-up (incidence rate, 3.1 cases per 1000 years at risk). In the school-aged children's cohort, 11,585 children (4.2%) experienced an asthmatic event during the seventh year of life. Dog exposure during the first year of life was associated with a decreased risk of asthma in school-aged children (OR, 0.87; 95% CI, 0.81-0.93) and in preschool-aged children 3 years or older (HR, 0.90; 95% CI, 0.83-0.99) but not in children younger than 3 years (HR, 1.03; 95% CI, 1.00-1.07). Results were comparable when analyzing only first-born children. Farm animal

  2. Polarity dependence of Mn incorporation in (Ga,Mn)N superlattices

    NASA Astrophysics Data System (ADS)

    Tropf, L.; Kunert, G.; Jakieła, R.; Wilhelm, R. A.; Figge, S.; Grenzer, J.; Hommel, D.

    2016-03-01

    In the context of recent efforts to combine high Mn concentrations in (Ga,Mn)N with a pronounced p-type carrier density, (Ga,Mn)N/GaN:Mg-superlattices have been fabricated using plasma-assisted molecular beam epitaxy. Profiles of the dopant atomic densities in the heterostructures are obtained by secondary ion mass spectroscopy. They show an abrupt drop of two to three orders of magnitude in both Mn and Mg concentrations after the first GaN:Mg layer above a critical Mg-flux. Scanning electron microscopy before and after selective etching reveals a polarity inversion from originally Ga-face to N-face GaN in samples in which high Mg fluxes were applied. From our observations, we are able to draw an analogy between the impurity incorporation laws of Mg and Mn.

  3. Prenatal exposure to neurotoxic metals is associated with increased placental glucocorticoid receptor DNA methylation

    PubMed Central

    Appleton, Allison A.; Jackson, Brian P.; Marsit, Carmen J.

    2017-01-01

    ABSTRACT Epigenetic alterations related to prenatal neurotoxic metals exposure may be key in understanding the origins of cognitive and neurobehavioral problems in children. Placental glucocorticoid receptor (NR3C1) methylation has been linked to neurobehavioral risk in early life, but has not been examined in response to neurotoxic metals exposure despite parallel lines of research showing metals exposure and NR3C1 methylation each contribute to a similar set of neurobehavioral phenotypes. Thus, we conducted a study of prenatal neurotoxic metals exposure and placental NR3C1 methylation in a cohort of healthy term singleton pregnancies from Rhode Island, USA (n = 222). Concentrations of arsenic (As; median 0.02 ug/g), cadmium (Cd; median 0.03 μg/g), lead (Pb; median 0.40 μg/g), manganese (Mn; median 0.56 μg/g), mercury (Hg; median 0.02 μg/g), and zinc (Zn; 145.18 μg/g) measured in infant toenails were categorized as tertiles. Multivariable linear regression models tested the independent associations for each metal with NR3C1 methylation, as well as the cumulative risk of exposure to multiple metals simultaneously. Compared to the lowest exposure tertiles, higher levels of As, Cd, Pb, Mn, and Hg were each associated with increased placental NR3C1 methylation (all P<0.02). Coefficients for these associations corresponded with a 0.71–1.41 percent increase in NR3C1 methylation per tertile increase in metals concentrations. For Zn, the lowest exposure tertile compared with the highest tertile was associated with 1.26 percent increase in NR3C1 methylation (P=0.01). Higher cumulative metal risk scores were marginally associated with greater NR3C1 methylation. Taken together, these results indicate that prenatal exposure to neurotoxic metals may affect the offspring's NR3C1 activity, which may help explain cognitive and neurodevelopmental risk later in life. PMID:28548590

  4. Prenatal exposure to neurotoxic metals is associated with increased placental glucocorticoid receptor DNA methylation.

    PubMed

    Appleton, Allison A; Jackson, Brian P; Karagas, Margaret; Marsit, Carmen J

    2017-08-01

    Epigenetic alterations related to prenatal neurotoxic metals exposure may be key in understanding the origins of cognitive and neurobehavioral problems in children. Placental glucocorticoid receptor (NR3C1) methylation has been linked to neurobehavioral risk in early life, but has not been examined in response to neurotoxic metals exposure despite parallel lines of research showing metals exposure and NR3C1 methylation each contribute to a similar set of neurobehavioral phenotypes. Thus, we conducted a study of prenatal neurotoxic metals exposure and placental NR3C1 methylation in a cohort of healthy term singleton pregnancies from Rhode Island, USA (n = 222). Concentrations of arsenic (As; median 0.02 ug/g), cadmium (Cd; median 0.03 μg/g), lead (Pb; median 0.40 μg/g), manganese (Mn; median 0.56 μg/g), mercury (Hg; median 0.02 μg/g), and zinc (Zn; 145.18 μg/g) measured in infant toenails were categorized as tertiles. Multivariable linear regression models tested the independent associations for each metal with NR3C1 methylation, as well as the cumulative risk of exposure to multiple metals simultaneously. Compared to the lowest exposure tertiles, higher levels of As, Cd, Pb, Mn, and Hg were each associated with increased placental NR3C1 methylation (all P<0.02). Coefficients for these associations corresponded with a 0.71-1.41 percent increase in NR3C1 methylation per tertile increase in metals concentrations. For Zn, the lowest exposure tertile compared with the highest tertile was associated with 1.26 percent increase in NR3C1 methylation (P=0.01). Higher cumulative metal risk scores were marginally associated with greater NR3C1 methylation. Taken together, these results indicate that prenatal exposure to neurotoxic metals may affect the offspring's NR3C1 activity, which may help explain cognitive and neurodevelopmental risk later in life.

  5. Early life exposure to traffic-related air pollution and allergic rhinitis in preschool children.

    PubMed

    Deng, Qihong; Lu, Chan; Yu, Yichen; Li, Yuguo; Sundell, Jan; Norbäck, Dan

    2016-12-01

    Evidence linking long-term exposure to outdoor air pollution with allergic rhinitis (AR) in children is scare, and the role of components of air pollution and timing of exposure remains unclear. To assess the association of pre- and post-natal exposure to air pollution with life-time prevalence of AR in preschool children. We conducted a cohort study of 2598 children aged 3-6 years in Changsha, China. The lifetime prevalence of AR was assessed by a questionnaire administered by parents. Children's exposures to dioxide nitrogen (NO 2 ), sulfur dioxide (SO 2 ) and particulate matter with an aerodynamic diameter ≤ 10 μm (PM 10 ) during different pre- and post-natal timing windows were estimated using the measured concentrations at monitoring stations. The odds ratio (OR) and 95% confidence interval (CI) of childhood AR for exposure to different air pollutants during different timing windows were assessed by logistic regression model in terms of an interquartile range (IQR) increase in exposure level. Life-time prevalence of AR in preschool children (7.3%) was associated with both pre- and post-natal exposure to traffic-related air pollution (TRAP), but only significant during the third trimester of pregnancy with adjusted OR = 1.40 (95% CI: 1.08-1.82) for a 15 μg/m 3 increase in NO 2 and during the first-year of life with adjusted OR = 1.36 (95% CI: 1.03-1.78) and 1.54 (95% CI: 1.07-2.21) respectively for 11 and 12 μg/m 3 increase in NO 2 and PM 10 . The association of early life exposure to TRAP with childhood AR was robust by adjusting for other air pollutants and timing windows. Sensitivity analysis indicated that the association was higher in the children who are male, young, with genetic predisposition by parental atopy, and living in damp houses. Early life exposure to traffic-related air pollutant during pregnancy and first-year of life may contribute to childhood AR. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Effect of Mn and Fe on the Formation of Fe- and Mn-Rich Intermetallics in Al–5Mg–Mn Alloys Solidified Under Near-Rapid Cooling

    PubMed Central

    Liu, Yulin; Huang, Gaoren; Sun, Yimeng; Zhang, Li; Huang, Zhenwei; Wang, Jijie; Liu, Chunzhong

    2016-01-01

    Mn was an important alloying element used in Al–Mg–Mn alloys. However, it had to be limited to a low level (<1.0 wt %) to avoid the formation of coarse intermetallics. In order to take full advantage of the benefits of Mn, research was carried out to investigate the possibility of increasing the content of Mn by studying the effect of cooling rate on the formation of Fe- and Mn-rich intermetallics at different content levels of Mn and Fe. The results indicated that in Al–5Mg–Mn alloy with low Fe content (<0.1 wt %), intermetallic Al6(Fe,Mn) was small in size and amount. With increasing Mn content, intermetallic Al6(Fe,Mn) increased, but in limited amount. In high-Fe-containing Al–5Mg–Mn alloys (0.5 wt % Fe), intermetallic Al6(Fe,Mn) became the dominant phase, even in the alloy with low Mn content (0.39 wt %). Cooling rate played a critical role in the refinement of the intermetallics. Under near-rapid cooling, intermetallic Al6(Fe,Mn) was extremely refined. Even in the high Mn and/or high-Fe-containing alloys, it still demonstrated fine Chinese script structures. However, once the alloy composition passed beyond the eutectic point, the primary intermetallic Al6(Fe,Mn) phase displayed extremely coarse platelet-like morphology. Increasing the content of Fe caused intermetallic Al6(Fe,Mn) to become the primary phase at a lower Mn content. PMID:28787888

  7. Effect of Mn and Fe on the Formation of Fe- and Mn-Rich Intermetallics in Al-5Mg-Mn Alloys Solidified Under Near-Rapid Cooling.

    PubMed

    Liu, Yulin; Huang, Gaoren; Sun, Yimeng; Zhang, Li; Huang, Zhenwei; Wang, Jijie; Liu, Chunzhong

    2016-01-29

    Mn was an important alloying element used in Al-Mg-Mn alloys. However, it had to be limited to a low level (<1.0 wt %) to avoid the formation of coarse intermetallics. In order to take full advantage of the benefits of Mn, research was carried out to investigate the possibility of increasing the content of Mn by studying the effect of cooling rate on the formation of Fe- and Mn-rich intermetallics at different content levels of Mn and Fe. The results indicated that in Al-5Mg-Mn alloy with low Fe content (<0.1 wt %), intermetallic Al₆(Fe,Mn) was small in size and amount. With increasing Mn content, intermetallic Al₆(Fe,Mn) increased, but in limited amount. In high-Fe-containing Al-5Mg-Mn alloys (0.5 wt % Fe), intermetallic Al₆(Fe,Mn) became the dominant phase, even in the alloy with low Mn content (0.39 wt %). Cooling rate played a critical role in the refinement of the intermetallics. Under near-rapid cooling, intermetallic Al₆(Fe,Mn) was extremely refined. Even in the high Mn and/or high-Fe-containing alloys, it still demonstrated fine Chinese script structures. However, once the alloy composition passed beyond the eutectic point, the primary intermetallic Al₆(Fe,Mn) phase displayed extremely coarse platelet-like morphology. Increasing the content of Fe caused intermetallic Al₆(Fe,Mn) to become the primary phase at a lower Mn content.

  8. Effects of early exposure to phthalates and bisphenols on cardiometabolic outcomes in pregnancy and childhood.

    PubMed

    Philips, Elise M; Jaddoe, Vincent W V; Trasande, Leonardo

    2017-03-01

    Pregnant women are exposed to various chemicals, including endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenols. Increasing evidence suggests that early life exposures to phthalates and bisphenols may contribute to cardiometabolic risks. The aim of this narrative review was to summarize current knowledge of the effects of fetal and childhood exposure to phthalates and bisphenols on child growth and child cardiometabolic outcomes and the effects on maternal outcomes. In total, 54 studies were identified and included. The majority of studies found effects of phthalates and bisphenols on maternal, child growth, and cardiometabolic outcomes. Currently results suggest that early life exposure to phthalates and bisphenols may have a substantial influence on perinatal and postnatal cardiometabolic programming. In a large part of the investigated outcomes studies show contradictory results. However, the majority of the existing evidence is based on non-cohort studies with single samples neglecting time-variant effects and complicating conclusions regarding causal inference. More studies are needed investigating the mechanisms and its potential interactions. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Magnetostriction-polarization coupling in multiferroic Mn 2MnWO 6

    DOE PAGES

    Li, Man-Rong; McCabe, Emma E.; Stephens, Peter W.; ...

    2017-12-11

    Double corundum-related polar magnets are promising materials for multiferroic and magnetoelectric applications in spintronics. However, their design and synthesis is a challenge, and magnetoelectric coupling has only been observed in Ni 3TeO 6 among the known double corundum compounds to date. Here in this paper we address the high-pressure synthesis of a new polar and antiferromagnetic corundum derivative Mn 2MnWO 6, which adopts the Ni 3TeO 6-type structure with low temperature first-order field-induced metamagnetic phase transitions (T N = 58 K) and high spontaneous polarization (~ 63.3 μC·cm -2). The magnetostriction-polarization coupling in Mn 2MnWO 6 is evidenced by secondmore » harmonic generation effect, and corroborated by magnetic-field-dependent pyroresponse behavior, which together with the magnetic-field-dependent polarization and dielectric measurements, qualitatively indicate magnetoelectric coupling. Finally, piezoresponse force microscopy imaging and spectroscopy studies on Mn 2MnWO 6 show switchable polarization, which motivates further exploration on magnetoelectric effect in single crystal/thin film specimens.« less

  10. Magnetostriction-polarization coupling in multiferroic Mn 2MnWO 6

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Man-Rong; McCabe, Emma E.; Stephens, Peter W.

    Double corundum-related polar magnets are promising materials for multiferroic and magnetoelectric applications in spintronics. However, their design and synthesis is a challenge, and magnetoelectric coupling has only been observed in Ni 3TeO 6 among the known double corundum compounds to date. Here in this paper we address the high-pressure synthesis of a new polar and antiferromagnetic corundum derivative Mn 2MnWO 6, which adopts the Ni 3TeO 6-type structure with low temperature first-order field-induced metamagnetic phase transitions (T N = 58 K) and high spontaneous polarization (~ 63.3 μC·cm -2). The magnetostriction-polarization coupling in Mn 2MnWO 6 is evidenced by secondmore » harmonic generation effect, and corroborated by magnetic-field-dependent pyroresponse behavior, which together with the magnetic-field-dependent polarization and dielectric measurements, qualitatively indicate magnetoelectric coupling. Finally, piezoresponse force microscopy imaging and spectroscopy studies on Mn 2MnWO 6 show switchable polarization, which motivates further exploration on magnetoelectric effect in single crystal/thin film specimens.« less

  11. Children’s Environmental Health in the Digital Era: Understanding Early Screen Exposure as a Preventable Risk Factor for Obesity and Sleep Disorders

    PubMed Central

    Wolf, Candice; Wolf, Seth; Weiss, Miriam; Nino, Gustavo

    2018-01-01

    The quantity, accessibility and focus on child-targeted programming has exponentially increased since it entered American households in the early 1900s. It may have started with the television (TV), but technology has evolved and now fits in our pockets; as of 2017, 95% of American families own a smartphone. Availability and child-tailored content has subsequently led to a decrease in the age at initial screen exposure. The negative effects that accompany the current culture of early screen exposure are extensive and need to be considered as technology continues to enter the home and inundate social interactions. Increased levels of early screen exposure have been associated with decreased cognitive abilities, decreased growth, addictive behavior, poor school performance, poor sleep patterns, and increased levels of obesity. Research on the adverse effects of early screen exposure is mounting, but further epidemiological studies are still needed to inform prevention and regulation policies. PMID:29473855

  12. Mn(II,III) oxidation and MnO 2 mineralization by an expressed bacterial multicopper oxidase

    DOE PAGES

    Butterfield, Cristina N.; Soldatova, Alexandra V.; Lee, Sung -Woo; ...

    2013-07-01

    Reactive Mn(IV) oxide minerals are ubiquitous in the environment and control the bioavailability and distribution of many toxic and essential elements and organic compounds. Their formation is thought to be dependent on microbial enzymes, because spontaneous Mn(II) to Mn(IV) oxidation is slow. Several species of marine Bacillus spores oxidize Mn(II) on their exosporium, the outermost layer of the spore, encrusting them with Mn(IV) oxides. Molecular studies have identified the mnx (Mn oxidation) genes, including mnxG, encoding a putative multicopper oxidase (MCO), as responsible for this two-electron oxidation, a surprising finding because MCOs only catalyze single-electron transfer reactions. Characterization of themore » enzymatic mechanism has been hindered by the lack of purified protein. By purifying active protein from the mnxDEFG expression construct, we found that the resulting enzyme is a blue (absorption maximum 590 nm) complex containing MnxE, MnxF, and MnxG proteins. Further, by analyzing the Mn(II)- and (III)-oxidizing activity in the presence of a Mn(III) chelator, pyrophosphate, we found that the complex facilitates both electron transfers from Mn(II) to Mn(III) and from Mn(III) to Mn(IV). X-ray absorption spectroscopy of the Mn mineral product confirmed its similarity to Mn(IV) oxides generated by whole spores. Our results demonstrate that Mn oxidation from soluble Mn(II) to Mn(IV) oxides is a two-step reaction catalyzed by an MCO-containing complex. Lastly, with the purification of active Mn oxidase, we will be able to uncover its mechanism, broadening our understanding of Mn mineral formation and the bioinorganic capabilities of MCOs.« less

  13. Mn(II,III) oxidation and MnO2 mineralization by an expressed bacterial multicopper oxidase

    PubMed Central

    Butterfield, Cristina N.; Soldatova, Alexandra V.; Lee, Sung-Woo; Spiro, Thomas G.; Tebo, Bradley M.

    2013-01-01

    Reactive Mn(IV) oxide minerals are ubiquitous in the environment and control the bioavailability and distribution of many toxic and essential elements and organic compounds. Their formation is thought to be dependent on microbial enzymes, because spontaneous Mn(II) to Mn(IV) oxidation is slow. Several species of marine Bacillus spores oxidize Mn(II) on their exosporium, the outermost layer of the spore, encrusting them with Mn(IV) oxides. Molecular studies have identified the mnx (Mn oxidation) genes, including mnxG, encoding a putative multicopper oxidase (MCO), as responsible for this two-electron oxidation, a surprising finding because MCOs only catalyze single-electron transfer reactions. Characterization of the enzymatic mechanism has been hindered by the lack of purified protein. By purifying active protein from the mnxDEFG expression construct, we found that the resulting enzyme is a blue (absorption maximum 590 nm) complex containing MnxE, MnxF, and MnxG proteins. Further, by analyzing the Mn(II)- and (III)-oxidizing activity in the presence of a Mn(III) chelator, pyrophosphate, we found that the complex facilitates both electron transfers from Mn(II) to Mn(III) and from Mn(III) to Mn(IV). X-ray absorption spectroscopy of the Mn mineral product confirmed its similarity to Mn(IV) oxides generated by whole spores. Our results demonstrate that Mn oxidation from soluble Mn(II) to Mn(IV) oxides is a two-step reaction catalyzed by an MCO-containing complex. With the purification of active Mn oxidase, we will be able to uncover its mechanism, broadening our understanding of Mn mineral formation and the bioinorganic capabilities of MCOs. PMID:23818588

  14. Mn(II,III) oxidation and MnO2 mineralization by an expressed bacterial multicopper oxidase

    NASA Astrophysics Data System (ADS)

    Butterfield, Cristina N.; Soldatova, Alexandra V.; Lee, Sung-Woo; Spiro, Thomas G.; Tebo, Bradley M.

    2013-07-01

    Reactive Mn(IV) oxide minerals are ubiquitous in the environment and control the bioavailability and distribution of many toxic and essential elements and organic compounds. Their formation is thought to be dependent on microbial enzymes, because spontaneous Mn(II) to Mn(IV) oxidation is slow. Several species of marine Bacillus spores oxidize Mn(II) on their exosporium, the outermost layer of the spore, encrusting them with Mn(IV) oxides. Molecular studies have identified the mnx (Mn oxidation) genes, including mnxG, encoding a putative multicopper oxidase (MCO), as responsible for this two-electron oxidation, a surprising finding because MCOs only catalyze single-electron transfer reactions. Characterization of the enzymatic mechanism has been hindered by the lack of purified protein. By purifying active protein from the mnxDEFG expression construct, we found that the resulting enzyme is a blue (absorption maximum 590 nm) complex containing MnxE, MnxF, and MnxG proteins. Further, by analyzing the Mn(II)- and (III)-oxidizing activity in the presence of a Mn(III) chelator, pyrophosphate, we found that the complex facilitates both electron transfers from Mn(II) to Mn(III) and from Mn(III) to Mn(IV). X-ray absorption spectroscopy of the Mn mineral product confirmed its similarity to Mn(IV) oxides generated by whole spores. Our results demonstrate that Mn oxidation from soluble Mn(II) to Mn(IV) oxides is a two-step reaction catalyzed by an MCO-containing complex. With the purification of active Mn oxidase, we will be able to uncover its mechanism, broadening our understanding of Mn mineral formation and the bioinorganic capabilities of MCOs.

  15. Generation of a Mn(IV)-Peroxo or Mn(III)-Oxo-Mn(III) Species upon Oxygenation of Mono- and Binuclear Thiolate-Ligated Mn(II) Complexes.

    PubMed

    Lee, Chien-Ming; Wu, Wun-Yan; Chiang, Ming-Hsi; Bohle, D Scott; Lee, Gene-Hsiang

    2017-09-05

    A thiolate-bridged binuclear complex [PPN] 2 [(Mn II ( TMS PS3)) 2 ] (1, PPN = bis(triphenylphosphine)iminium and TMS PS3H 3 = (2,2',2″-trimercapto-3,3',3″-tris(trimethylsilyl)triphenylphosphine)), prepared from the reaction of MnCl 2 /[PPN]Cl and Li 3 [ TMS PS3], converts into a mononuclear complex [PPN][Mn II ( TMS PS3)(DABCO)] (2) in the presence of excess amounts of DABCO (DABCO = 1,4-diazabicyclo[2.2.2]octane). Variable temperature studies of solution containing 1 and DABCO by UV-vis spectroscopy indicate that 1 and 2 exist in significant amounts in equilibrium and mononuclear 2 is favored at low temperature. Treatment of 1 or 2 with the monomeric O 2 -side-on-bound [PPN][Mn IV (O 2 )( TMS PS3)] (3) produces the mono-oxo-bridged dimer [PPN] 2 [(Mn III ( TMS PS3)) 2 (μ-O)] (4). The electrochemistry of 1 and 2 reveals anodic peak(s) for a Mn III/ Mn II redox couple at shifted potentials against Fc/Fc + , indicating that both complexes can be oxidized by dioxygen. The O 2 activation mediated by 1 and 2 is investigated in both solution and the solid state. Microcrystals of 2 rapidly react with air or dry O 2 to generate the Mn(IV)-peroxo 3 in high yield, revealing a solid-to-solid transformation and two-electron reduction of O 2 . Oxygenation of 1 or 2 in solution, however, is affected by diffusion and transient concentration of dioxygen in the two different substrates, leading to generation of 3 and 4 in variable ratios.

  16. Magnetic properties of single-phase MnBi grown from MnBi{sub 49} melt

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xiao, X. F.; Si, P. Z., E-mail: pzsi@cjlu.edu.cn; Feng, H.

    2014-05-07

    The single-phase NiAs-type MnBi, embedded in Bi matrix, was grown from homogeneous MnBi{sub 49} melt at low temperatures to prevent the formation of Mn{sub 1.08}Bi. An abrupt magnetization change was observed at ∼240 K. The origin of this change was ascribed to the movement of the Mn atoms between the regular sites and the interstitial sites in the MnBi lattices. The splitting of the x-ray photoelectron lines of MnBi indicates the presence of two binding states of Mn atoms, one of which was ascribed to interstitial Mn atoms. A large coercivity up to 1.79 T at 400 K was observed in the as-grownmore » bulk isotropic MnBi alloys.« less

  17. Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.

    PubMed

    Auiler, J F; Liu, K; Lynch, J M; Gelotte, C K

    2002-01-01

    Stimulant therapy is the mainstay of treatment for children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Once-daily, extended-release oral formulations offer long acting control of symptoms by modifying drug delivery and absorption. In particular, consistency in early drug exposure is important for symptom control during school or work hours. Because these once-daily formulations are usually taken in the morning, the timing of the doses with breakfast is important. This study compared the effect of a high-fat breakfast on early drug exposure from a morning dose of two extended-release stimulant formulations: the osmotic-controlled OROS tablet of methylphenidate HCI (CONCERTA) and the capsule containing extended-release beads of mixed amphetamine salts (ADDERALL XR). The study had a single-dose, open-label, randomised, four-treatment, crossover design in which healthy subjects received either 36 mg CONCERTA or 20 mg ADDERALL XR in the morning after an overnight fast or a high-fat breakfast. Serial blood samples were collected over 28h to determine plasma concentrations of methylphenidate and amphetamine. The food effect on early drug exposure and the pharmacokinetic profiles up to 8 h after dosing of the two extended-release stimulants were directly compared using partial area (AUC(p4h), AUC(p6h) and AUC(p8h)) fed/fasted ratios. Amphetamine concentrations were markedly lower when the subjects had eaten breakfast, resulting in lower early drug exposures (p < 0.0001). By contrast, methylphenidate concentrations over the same 8 h were unaffected by breakfast, providing consistent levels of early drug exposure. Therefore, as a child's or adult's eating pattern varies, methylphenidate exposure over the first 8 h would be expected to have less day-to-day variation compared with amphetamine exposure. The osmotic-controlled OROS tablet provides a reliable and consistent delivery of methylphenidate HCI, independent of food, for patients with

  18. Chains of risk for alcohol use disorder: Mediators of exposure to neighborhood deprivation in early and middle childhood.

    PubMed

    Karriker-Jaffe, Katherine J; Lönn, Sara L; Cook, Won K; Kendler, Kenneth S; Sundquist, Kristina

    2018-03-01

    Our goal was to test a cascade model to identify developmental pathways, or chains of risk, from neighborhood deprivation in childhood to alcohol use disorder (AUD) in young adulthood. Using Swedish general population data, we examined whether exposure to neighborhood deprivation during early and middle childhood was associated with indicators of social functioning in adolescence and emerging adulthood, and whether these were predictive of AUD. Structural equation models showed exposure to neighborhood deprivation was associated with lower school achievement during adolescence, poor social functioning during emerging adulthood, and the development of AUD for both males and females. Understanding longitudinal pathways from early exposure to adverse environments to later AUD can inform prevention and intervention efforts. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Neuromotor function in ship welders after cessation of manganese exposure.

    PubMed

    Wastensson, Gunilla; Sallsten, Gerd; Bast-Pettersen, Rita; Barregard, Lars

    2012-08-01

    The aim of the present study was to investigate whether previous long-term exposure to manganese (Mn) via inhalation of welding fumes can cause persistent impairment in neuromotor function even long after cessation of exposure. Quantitative tests of tremor, motor speed, manual dexterity, diadochokinesis, eye-hand coordination and postural stability were administered to 17 retired ship welders (mean age 69 years), with mean exposure time 28 years. The welders' exposure had ceased on average 18 years before the study. A cumulative exposure index (CEI) was calculated for each of the former welders. The welders were compared with 21 referents from the same shipyards (mean age was 66 years). Former welders performed less well than referents in the grooved pegboard test, and poorer performance was associated with CEI. The performance in most of the other neurobehavioral tests was similar between groups, but the welders tended to perform slightly better than the referents in tests demanding hand steadiness. The latter finding may be due to a training effect from their former working tasks or selection bias into or out of this occupation. In the present study of welders with previous welding fume exposure, former welders and referents performed similarly in most of the neurobehavioral tests. Previous adverse effects on the neuromotor system might have ceased, and decreased neuromotor function due to normal aging processes in both groups might have disguised any slight effect of previous Mn exposure. The poorer performance in the grooved pegboard test among welders may indicate an adverse effect on motor function of long-term exposure to Mn, but this finding has to be confirmed by other studies.

  20. In situ TEM observation of novel chemical evolution of MnBr2 catalyzed by Cu under electron beam irradiation

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Bai, Xianwei; Guan, Xiangxiang; Shen, Xi; Yao, Yuan; Wang, Yanguo; Zou, Bingsuo; Yu, Richeng

    2017-10-01

    Manganese bromide has attracted enormous attention for its applications in the syntheses of organic-inorganic hybrid compounds. A complete understanding of structural and chemical stabilities of MnBr2 is important for controlling its properties. Here, we focus on the irradiation resistance of MnBr2. The chief purpose of this research is reached by in situ transmission electron microscopy. It is demonstrated that the deliquescent MnBr2 powder is prone to adsorb the vapor in air, and the hydrous MnBr2 can be decomposed under its continuous exposure to electron beam, indicated by a transmission electron microscope via the catalysis of Cu grid at room temperature.

  1. Assessment of health risks resulting from early-life exposures: Are current chemical toxicity testing protocols and risk assessment methods adequate?

    PubMed

    Felter, Susan P; Daston, George P; Euling, Susan Y; Piersma, Aldert H; Tassinari, Melissa S

    2015-03-01

    Abstract Over the last couple of decades, the awareness of the potential health impacts associated with early-life exposures has increased. Global regulatory approaches to chemical risk assessment are intended to be protective for the diverse human population including all life stages. However, questions persist as to whether the current testing approaches and risk assessment methodologies are adequately protective for infants and children. Here, we review physiological and developmental differences that may result in differential sensitivity associated with early-life exposures. It is clear that sensitivity to chemical exposures during early-life can be similar, higher, or lower than that of adults, and can change quickly within a short developmental timeframe. Moreover, age-related exposure differences provide an important consideration for overall susceptibility. Differential sensitivity associated with a life stage can reflect the toxicokinetic handling of a xenobiotic exposure, the toxicodynamic response, or both. Each of these is illustrated with chemical-specific examples. The adequacy of current testing protocols, proposed new tools, and risk assessment methods for systemic noncancer endpoints are reviewed in light of the potential for differential risk to infants and young children.

  2. A hierarchical nanostructure consisting of amorphous MnO 2, Mn 3O 4 nanocrystallites, and single-crystalline MnOOH nanowires for supercapacitors

    NASA Astrophysics Data System (ADS)

    Hu, Chi-Chang; Hung, Ching-Yun; Chang, Kuo-Hsin; Yang, Yi-Lin

    In this communication, a porous hierarchical nanostructure consisting of amorphous MnO 2 (a-MnO 2), Mn 3O 4 nanocrystals, and single-crystalline MnOOH nanowires is designed for the supercapacitor application, which is prepared by a simple two-step electrochemical deposition process. Because of the gradual co-transformation of Mn 3O 4 nanocrystals and a-MnO 2 nanorods into an amorphous manganese oxide, the cycle stability of a-MnO 2 is obviously enhanced by adding Mn 3O 4. This unique ternary oxide nanocomposite with 100-cycle CV activation exhibits excellent capacitive performances, i.e., excellent reversibility, high specific capacitances (470 F g -1 in CaCl 2), high power property, and outstanding cycle stability. The highly porous microstructures of this composite before and after the 10,000-cycle CV test are examined by means of scanning electron microscopy (SEM) and transmission electron microscopy (TEM).

  3. Prolonged Exposure Therapy for a Vietnam Veteran with PTSD and Early-Stage Dementia

    ERIC Educational Resources Information Center

    Duax, Jeanne M.; Waldron-Perrine, Brigid; Rauch, Sheila A. M.; Adams, Kenneth M.

    2013-01-01

    Although prolonged exposure therapy (PE) is considered an evidence-based treatment for PTSD, there has been little published about the use of this treatment for older adults with comorbid early-stage dementia. As the number of older adults in the United States continues to grow, so will their unique mental health needs. The present article…

  4. Prenatal exposure to disaster-related traumatic stress and developmental trajectories of temperament in early childhood: Superstorm Sandy pregnancy study.

    PubMed

    Zhang, Wei; Rajendran, Khushmand; Ham, Jacob; Finik, Jackie; Buthmann, Jessica; Davey, Kei; Pehme, Patricia M; Dana, Kathryn; Pritchett, Alexandra; Laws, Holly; Nomura, Yoko

    2018-07-01

    Little is known about the impact of prenatal maternal stress (PNMS) on the developmental trajectory of temperament and few studies have been able to incorporate a natural disaster as a quasi-experimental stressor. The current study investigated PNMS related to Superstorm Sandy ('Sandy'), a hurricane that struck the New York metropolitan area in October 2012, in terms of objective exposure during pregnancy, subjective stress reaction as assessed by maternal symptoms of post-traumatic stress, and their impact on the developmental changes in temperament during early childhood. A subsample of 318 mother-child dyads was drawn from the Stress in Pregnancy Study. Temperament was measured at 6, 12, 18, and 24 months of age. Objective exposure was associated with greater High-Intensity Pleasure, Approach, Perceptual Sensitivity and Fearfulness, but lower Cuddliness and Duration of Orientation at 6 months. Objective exposure and its interaction with subjective stress reaction predicted developmental changes in temperament. In particular, objective exposure was linked to greater increases in Activity Level but decreases in High-Intensity Pleasure, Approach, and Fearfulness. The combination of objective exposure and subjective stress reaction was also associated with greater increases in Activity Level. Temperament was measured solely via maternal report. Trimester-specific effects of Sandy on temperament were not examined. This is the first study to examine the effects of prenatal maternal exposure to a natural disaster on trajectories of early childhood temperament. Findings suggest that both objective stress exposure and subjective stress reaction in-utero predict developmental trajectories of temperament in early childhood. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Dental caries and fluorosis experience of 8-12-year-old children by early-life exposure to fluoride.

    PubMed

    Do, Loc G; Miller, Jenifer; Phelan, Claire; Sivaneswaran, Shanti; Spencer, A John; Wright, Clive

    2014-12-01

    It is important to evaluate concurrently the benefit for dental caries and the risk for dental fluorosis from early exposure to fluoride among children. To evaluate associations of different levels of exposure to fluoride in early childhood with dental caries and dental fluorosis experience in school children. A Child Dental Health Survey (CDHS) was conducted among school children in the Australian state of New South Wales (NSW) in 2007. Trained and calibrated examination teams conducted oral epidemiologic examinations to assess caries experience as decayed, missing or filled tooth surfaces of the primary and permanent dentitions (dmfs/DMFS) and fluorosis using the Thylstrup & Fejerskov (TF) index on the maxillary central incisors only. A parental questionnaire collected information on residential histories and tap water usage to enable calculation of percentage of 3-year lifetime exposure to fluoride in water. Use of dietary fluoride supplements was also collected. Dental caries and fluorosis experience were compared among groups by levels of exposure to fluoride from water and fluoride supplements in bivariate and multivariable analysis, controlling for socioeconomic factors. Exposure to different fluoride sources varied in the group of 2611 children aged 8-12 years. Lower household income was significantly associated in both bivariate and multivariable analyses with the greater prevalence and severity of primary tooth caries among 8-10-year-old children and permanent tooth caries among 8-12 year old. Exposure to fluoride in water during the first 3 years of life was associated with both caries and fluorosis experience observed at age 8-12 years. Having higher percentage of 3-year lifetime exposure to fluoride in water was associated with higher prevalence of mostly mild fluorosis, but significantly lower prevalence and severity of caries in the primary and permanent dentitions. There were significant associations of dental caries and fluorosis experience with

  6. The nervous system effects of occupational exposure on workers in a South African manganese smelter.

    PubMed

    Myers, Jonathan E; Thompson, Mary Lou; Ramushu, Suzan; Young, Taryn; Jeebhay, Mohamed F; London, Leslie; Esswein, Eric; Renton, Kevin; Spies, Adri; Boulle, Andrew; Naik, Inakshi; Iregren, Anders; Rees, David J

    2003-12-01

    Five hundred and nine production workers at a manganese (Mn) smelting works comprising eight production facilities and 67 external controls were studied cross-sectionally for Mn related neuroehavioural effects. Exposure measures from personal sampling included Mn in inhalable dust as cumulative exposure indices (CEI) and average intensity (INT). Biological exposure and biological effect measures included blood (MnB), urine (MnU) manganese and serum prolactin. Endpoints included items from the Swedish nervous system questionnaire (Q16), World Health Organisation neurobehavioural core test battery (WHO NCTB), Swedish performance evaluation system (SPES), Luria-Nebraska (LN), and Danish product development (DPD) test batteries, and a brief clinical examination. Potential confounders and effect modifiers included age, educational level, alcohol and tobacco consumption, neurotoxic exposures in previous work, past medical history, previous head injury and home language. Associations were evaluated by multiple linear and logistic regression modelling. Modelling assumptions were tested. Average exposure intensity across all jobs ranged from near 0 (0.06 microg/m3) for external controls to 5.08 mg/m3 for inhalable Mn, and was greater than the ACGIH TLV for 69% of subjects. Results from the large number of tests performed resolved into three groups. Group 1 shows differences between external unexposed referents and all the exposed and/or differences between internal low exposed referents and the rest of the exposed but no further exposure-response relationships. It includes the Santa Ana, Benton and digit-span tests from the WHO NCTB; the hand tapping and endurance tapping tests from the SPES; Luria-Nebraska item 2L; questionnaire items tired, depressed, irritated, having to take notes in order to remember things, and subjects' perception that they had sex less often than normal; a test of clinical abnormality; and increased sway under two conditions (eyes open without foot

  7. Paramagnetic resonance of Mn4+ and Mn2+ centers in lanthanum gallate single crystals

    NASA Astrophysics Data System (ADS)

    Vazhenin, V. A.; Potapov, A. P.; Guseva, V. B.; Artyomov, M. Yu.

    2010-03-01

    An increase in the manganese concentration in lanthanum gallate in the range 0.5-5.0% has been found to result in a complete replacement of individual Mn4+ ions by Mn2+ ions. The relative concentrations and binding energies of individual Mn4+, Mn3+, and Mn2+ ions have been determined. The spin Hamiltonians of the Mn2+ and Mn4+ centers in the rhombohedral and orthorhombic phases, respectively, have been constructed and the orientation of the principal axes of the fine-structure tensor of Mn4+ at room temperature has been found. The possibility of using electron paramagnetic resonance for determining the rotation angles of oxygen octahedra of lanthanum gallate with respect to the perovskite structure has been discussed.

  8. Growth, Development, and Behavior in Early Childhood Following Prenatal Cocaine Exposure

    PubMed Central

    Frank, Deborah A.; Augustyn, Marilyn; Knight, Wanda Grant; Pell, Tripler; Zuckerman, Barry

    2008-01-01

    Context Despite recent studies that failed to show catastrophic effects of prenatal cocaine exposure, popular attitudes and public policies still reflect the belief that cocaine is a uniquely dangerous teratogen. Objective To critically review outcomes in early childhood after prenatal cocaine exposure in 5 domains: physical growth; cognition; language skills; motor skills; and behavior, attention, affect, and neurophysiology. Data Sources Search of MEDLINE and Psychological Abstracts from 1984 to October 2000. Study Selection Studies selected for detailed review (1) were published in a peerreviewed English-language journal; (2) included a comparison group; (3) recruited samples prospectively in the perinatal period; (4) used masked assessment; and (5) did not include a substantial proportion of subjects exposed in utero to opiates, amphetamines, phencyclidine, or maternal human immunodeficiency virus infection. Data Extraction Thirty-six of 74 articles met criteria and were reviewed by 3 authors. Disagreements were resolved by consensus. Data Synthesis After controlling for confounders, there was no consistent negative association between prenatal cocaine exposure and physical growth, developmental test scores, or receptive or expressive language. Less optimal motor scores have been found up to age 7 months but not thereafter, and may reflect heavy tobacco exposure. No independent cocaine effects have been shown on standardized parent and teacher reports of child behavior scored by accepted criteria. Experimental paradigms and novel statistical manipulations of standard instruments suggest an association between prenatal cocaine exposure and decreased attentiveness and emotional expressivity, as well as differences on neurophysiologic and attentional/affective findings. Conclusions Among children aged 6 years or younger, there is no convincing evidence that prenatal cocaine exposure is associated with developmental toxic effects that are different in severity

  9. Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

    PubMed

    Flores-Montoya, Mayra Gisel; Sobin, Christina

    2015-07-01

    Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1). Copyright © 2014 John Wiley & Sons, Ltd.

  10. Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

    PubMed Central

    Flores-Montoya, Mayra Gisel; Sobin, Christina

    2014-01-01

    Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams’ drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 μg dl−1). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 μg dl−1. PMID:25219894

  11. Fourier transform infrared emission spectra of MnH and MnD

    NASA Astrophysics Data System (ADS)

    Gordon, Iouli E.; Appadoo, Dominique R. T.; Shayesteh, Alireza; Walker, Kaley A.; Bernath, Peter F.

    2005-01-01

    Fourier transform infrared emission spectra of MnH and MnD were observed in the ground X7Σ + electronic state. The vibration-rotation bands from v = 1 → 0 to v = 3 → 2 for MnH and from v = 1 → 0 to v = 4 → 3 for MnD were recorded at an instrumental resolution of 0.0085 cm -1. Spectroscopic constants were determined for each vibrational level and equilibrium constants were found from a Dunham-type fit. The equilibrium vibrational constant ( ωe) for MnH was found to be 1546.84518(65) cm -1, the equilibrium rotational constant ( Be) is 5.6856789(103) cm -1 and the eqilibrium bond distance ( re) was determined to be 1.7308601(47) Å.

  12. Geochemistry of the Nsuta Mn deposit in Ghana: Implications for the Paleoproterozoic atmosphere and ocean chemistry

    NASA Astrophysics Data System (ADS)

    Goto, K. T.; Ito, T.; Suzuki, K.; Kashiwabara, T.; Takaya, Y.; Shimoda, G.; Nozaki, T.; Kiyokawa, S.; Tetteh, G. M.; Nyame, F. K.

    2013-12-01

    Oxygenation of the atmosphere and oceans has influenced the evolution of ocean chemistry and diversification of early life. A number of large manganese (Mn) deposits are distributed in the Paleoproterozoic sedimentary successions that were formed during the great oxidation event (GOE) around 2.4-2.2 Ga (Meynard, 2010). Due to the high redox potential of Mn, occurrences of Mn deposits have been regarded as important evidence for a highly oxidized environment during the Paleoproterozoic (Kirschvink et al., 2000). Furthermore, because Mn oxides strongly adsorb various elements, including bioessential elements such as Mo, formation of large Mn deposits may have affected the seawater chemical composition and ecology during the Paleoproterozoic. However, the genesis of each Mn deposit is poorly constrained, and the relationships among the formation of Mn deposits, the evolution of atmospheric and ocean chemistry, and the diversification of early life are still ambiguous. In this study, we report the Re-Os isotope compositions, rare earth element (REE) compositions, and abundance of manganophile elements in the Mn carbonate ore and host sedimentary rock samples collected from the Nsuta Mn deposit of the Birimian Supergroup, Ghana. The Nsuta deposit is one of the largest Paleoproterozoic Mn deposits, although its genesis remains controversial (Melcher et al., 1995; Mucke et al., 1999). The composite Re-Os isochron age (2149 × 130 Ma) of the Mn carbonate and sedimentary rock samples was consistent with the depositional age of the sedimentary rocks (~2.2 Ga) presumed from the U-Pb zircon age of volcanic rocks (Hirdes and Davis, 1998), suggesting that the timing of Mn ore deposition was almost equivalent to the host rock sedimentation. The PAAS-normalized REE pattern showed a positive Eu anomaly in all samples and a positive Ce anomaly only in the Mn carbonate ore. These REE patterns indicate the possible contribution of Eu-enriched fluids derived from hydrothermal activity

  13. Early Childhood Household Smoke Exposure Predicts Less Task-Oriented Classroom Behavior at Age 10

    ERIC Educational Resources Information Center

    Pagani, Linda S.; Fitzpatrick, Caroline

    2016-01-01

    Secondhand tobacco smoke is considered a developmental neurotoxicant especially given underdeveloped vital systems in young children. An ecological test of its negative influence on brain development can be made by examining the prospective association between early childhood household smoke exposure and later classroom behavior. Using a…

  14. Mn-53-Cr-53 Systematics of R-Chondrite NWA 753

    NASA Technical Reports Server (NTRS)

    Jogo, K.; Shih, C-Y.; Reese, Y. D.; Nyquist, L. E.

    2006-01-01

    Chondrules and chondrites are interpreted as objects formed in the early solar system, and it is important to study them in order to elucidate its evolution. Here, we report the study of the Mn-Cr systematics of the R-Chondrite NWA753 and compare the results to other chondrite data. The goal was to determine Cr isotopic and age variations among chondrite groups with different O-isotope signatures. The Mn-53-Cr-53 method as applied to individual chondrules [1] or bulk chondrites [2] is based on the assumption that 53Mn was initially homogeneously distributed in that portion the solar nebula where the chondrules and/or chondrites formed. However, different groups of chondrites formed from regions of different O-isotope compositions. So, different types of chondrites also may have had different initial Mn-53 abundances and/or Cr isotopic compositions. Thus, it is important to determine the Cr isotopic systematics among chondrites from various chondrite groups. We are studying CO-chondrite ALH83108 and Tagish Lake in addition to R-Chondrite NWA753. These meteorites have very distinct O-isotope compositions (Figure 1).

  15. Exposure to the Chinese famine in early life and the risk of anaemia in adulthood

    PubMed Central

    2013-01-01

    Background Famine exposure during the early stage of life is related to a number of adulthood diseases. The objective of this study was to examine the association of early life exposure to the famine in China (1959–1961) with the risk of anaemia in adulthood. Methods We used the data of 2007 adults born between 1954 and 1964 in Jiangsu province from the 2002 Chinese National Nutrition and Health Survey. Anaemia was defined as haemoglobin concentration <12 g/dl in women and <13 g/dl in men. Results Prevalence of anaemia in adulthood in nonexposed, fetal-exposed, early-childhood, mid-childhood, and late-childhood exposed to famine groups were 26.0%, 33.8%, 28.1%, 28.2% and 29.7%, respectively. Overall, fetal-exposed to famine was associated with 37% increased risk of anaemia as compared with those non-exposed after adjusting for income, education, place of residence, smoking, alcohol drinking, job, hypertension and BMI; relative risk (95% confidence interval) (RR (95% CI)) was 1.37 (1.09, 1.71). In general, this association appeared to be stronger among men, those who were currently overweight or obese, or those of lower educational levels. Corresponding RR (95% CI) was 1.87 (1.21-2.87), 1.75 (1.20-2.56), and 2.07 (1.37-3.12), respectively. Conclusions Fetal exposure to the Chinese famine was associated with an increased risk of anaemia in adulthood. PMID:24079608

  16. Raw milk consumption and other early-life farm exposures and adult pulmonary function in the Agricultural Lung Health Study.

    PubMed

    Wyss, Annah B; House, John S; Hoppin, Jane A; Richards, Marie; Hankinson, John L; Long, Stuart; Henneberger, Paul K; Beane Freeman, Laura E; Sandler, Dale P; O'Connell, Elizabeth Long; Cummings, Christie Barker; Umbach, David M; London, Stephanie J

    2018-03-01

    Literature suggests that early exposure to the farming environment protects against atopy and asthma; few studies have examined pulmonary function. We evaluated associations between early-life farming exposures and pulmonary function in 3061 adults (mean age=63) from a US farming population using linear regression. Childhood raw milk consumption was associated with higher FEV 1 (β=49.5 mL, 95% CI 2.8 to 96.1 mL, p=0.04) and FVC (β=66.2 mL, 95% CI 13.2 to 119.1 mL, p=0.01). We did not find appreciable associations with other early-life farming exposures. We report a novel association between raw milk consumption and higher pulmonary function that lasts into older adulthood. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Local surrounding of Mn in LaMn 1-xCo xO 3 compounds by means of EXAFS on Mn-K

    NASA Astrophysics Data System (ADS)

    Procházka, Vít; Sikora, Marcin; Kapusta, Czeslaw; Štěpánková, Helena; Chlan, Vojtěch; Knížek, Karel; Jirák, Zdeněk

    2010-05-01

    A systematic study of LaMn 1-xCo xO 3 perovskite series by means of X-ray absorption spectroscopy in the extended X-ray absorption fine structure (EXAFS) range of the K-absorption edge of Mn is reported. The Mn-K edge absorption measurements in the EXAFS region were performed to study the local surrounding of Mn ions. Polycrystalline powder samples of LaMn 1-xCo xO 3 ( x=0, 0.02; 0.2; 0.4; 0.5; 0.6; 0.8) prepared by solid-state reaction were used. The EXAFS spectra were analyzed with the FEFF8 computer program. The Mn-O distances of Mn to the nearest oxygen surroundings were evaluated for the samples in the series and compared with the Co-O distances obtained by EXAFS in V. Procházka et al., JMMM 310 (2007) 197 and with results of X-ray powder diffraction in C. Autret, J. Phys. Condens. Matter 17 (2005) 1601.

  18. ENDOR/ESR of Mn atoms and MnH molecules in solid argon

    NASA Astrophysics Data System (ADS)

    van Zee, R. J.; Garland, D. A.; Weltner, W., Jr.

    1986-09-01

    Mn atoms and MnH molecules, the latter formed by reaction between metal and hydrogen atoms, were trapped in solid argon and their ESR/ENDOR spectra measured at 4 K. At each pumping magnetic field two ENDOR lines were observed for 55Mn(I=5/2) atoms, corresponding to hyperfine transitions within the MS =±1/2 levels. Values of the hyperfine interaction constant and nuclear moment of 55Mn were derived from the six sets of data. For MnH, three sets of signals were detected: a proton ``matrix ENDOR'' line, transitions in the MS =0,±1 levels involving MI (55Mn)=1/2, 3/2, 5/2 levels, and proton transitions corresponding to νH and νH±aH. Analysis yielded the hyperfine constant aH =6.8(1) MHz and the nuclear quadrupole coupling constant Q'(55Mn)=-11.81(2) MHz. The latter compared favorably with a theoretical value derived earlier by Bagus and Schaefer. A higher term in the spin Hamiltonian appeared to be necessary to fit the proton hyperfine data.

  19. Effect of Hfe Deficiency on Memory Capacity and Motor Coordination after Manganese Exposure by Drinking Water in Mice

    PubMed Central

    Alsulimani, Helal Hussain; Ye, Qi

    2015-01-01

    Excess manganese (Mn) is neurotoxic. Increased manganese stores in the brain are associated with a number of behavioral problems, including motor dysfunction, memory loss and psychiatric disorders. We previously showed that the transport and neurotoxicity of manganese after intranasal instillation of the metal are altered in Hfe-deficient mice, a mouse model of the iron overload disorder hereditary hemochromatosis (HH). However, it is not fully understood whether loss of Hfe function modifies Mn neurotoxicity after ingestion. To investigate the role of Hfe in oral Mn toxicity, we exposed Hfe-knockout (Hfe-/-) and their control wild-type (Hfe+/+) mice to MnCl2 in drinking water (5 mg/mL) for 5 weeks. Motor coordination and spatial memory capacity were determined by the rotarod test and the Barnes maze test, respectively. Brain and liver metal levels were analyzed by inductively coupled plasma mass spectrometry. Compared with the water-drinking group, mice drinking Mn significantly increased Mn concentrations in the liver and brain of both genotypes. Mn exposure decreased iron levels in the liver, but not in the brain. Neither Mn nor Hfe deficiency altered tissue concentrations of copper or zinc. The rotarod test showed that Mn exposure decreased motor skills in Hfe+/+ mice, but not in Hfe-/- mice (p = 0.023). In the Barns maze test, latency to find the target hole was not altered in Mn-exposed Hfe+/+ compared with water-drinking Hfe+/+ mice. However, Mn-exposed Hfe-/- mice spent more time to find the target hole than Mn-drinking Hfe+/+ mice (p = 0.028). These data indicate that loss of Hfe function impairs spatial memory upon Mn exposure in drinking water. Our results suggest that individuals with hemochromatosis could be more vulnerable to memory deficits induced by Mn ingestion from our environment. The pathophysiological role of HFE in manganese neurotoxicity should be carefully examined in patients with HFE-associated hemochromatosis and other iron overload

  20. Effect of Hfe Deficiency on Memory Capacity and Motor Coordination after Manganese Exposure by Drinking Water in Mice.

    PubMed

    Alsulimani, Helal Hussain; Ye, Qi; Kim, Jonghan

    2015-12-01

    Excess manganese (Mn) is neurotoxic. Increased manganese stores in the brain are associated with a number of behavioral problems, including motor dysfunction, memory loss and psychiatric disorders. We previously showed that the transport and neurotoxicity of manganese after intranasal instillation of the metal are altered in Hfe-deficient mice, a mouse model of the iron overload disorder hereditary hemochromatosis (HH). However, it is not fully understood whether loss of Hfe function modifies Mn neurotoxicity after ingestion. To investigate the role of Hfe in oral Mn toxicity, we exposed Hfe-knockout (Hfe (-/-)) and their control wild-type (Hfe (+/+)) mice to MnCl2 in drinking water (5 mg/mL) for 5 weeks. Motor coordination and spatial memory capacity were determined by the rotarod test and the Barnes maze test, respectively. Brain and liver metal levels were analyzed by inductively coupled plasma mass spectrometry. Compared with the water-drinking group, mice drinking Mn significantly increased Mn concentrations in the liver and brain of both genotypes. Mn exposure decreased iron levels in the liver, but not in the brain. Neither Mn nor Hfe deficiency altered tissue concentrations of copper or zinc. The rotarod test showed that Mn exposure decreased motor skills in Hfe (+/+) mice, but not in Hfe (-/-) mice (p = 0.023). In the Barns maze test, latency to find the target hole was not altered in Mn-exposed Hfe (+/+) compared with water-drinking Hfe (+/+) mice. However, Mn-exposed Hfe (-/-) mice spent more time to find the target hole than Mn-drinking Hfe (+/+) mice (p = 0.028). These data indicate that loss of Hfe function impairs spatial memory upon Mn exposure in drinking water. Our results suggest that individuals with hemochromatosis could be more vulnerable to memory deficits induced by Mn ingestion from our environment. The pathophysiological role of HFE in manganese neurotoxicity should be carefully examined in patients with HFE-associated hemochromatosis and

  1. Induction of genomic instability after an acute whole-body exposure of mice to 56Fe ions

    NASA Astrophysics Data System (ADS)

    Rithidech, Kanokporn; Supanpaiboon, Wisa; Whorton, Elbert

    collected from CBA/CaJ and C57BL/6J mice at different times up to 3 months following an acute whole-body exposure to various doses of 1 GeV/amu 56 Fe ions (0, 0.1, 0.5 and 1.0 cGy) or 137 Cs gamma rays (0, 0.5, 1.0 and 3.0 cGy, as a reference radiation). These strains of mouse are known to be sensitive (CBA/CaJ) or resistant (C57BL/6J) to radiation-induced chromosomal damage and AML. At 2 days after the exposure, our data indicated that there was no increase in the frequency of MN-PCEs in CBA/CaJ mice exposed to 56 Fe ions while the frequency of MN-PCEs elevated as a function of dose in the C57BL/6J mice. At day 4, there was no dose related increase in either strain of mouse exposed to either 56 Fe ions or 137 Cs gamma rays. We also found that at the early sacrifice times (2 and 4 days) the 56 Fe ions were slightly more effective, per unit dose, in inducing MN-NCEs than 137 Cs gamma rays in both strains. Likewise, no increase in the frequency of MN-NCEs was found at late times after an acute exposure to either type of radiation. In contrast, both types of radiation induced increased MN-PCE frequencies in irradiated CBA/CaJ mice, but not C57BL/6J mice, at late times post-exposure. This finding indicates the potential induction of genomic instability in hematopoietic cells of CBA/CaJ mice by both types of radiation. The finding also demonstrates the influence of genetic background on radiation-induced genomic instability in vivo. Research funded by NASA Grant #NAG9- 1 52 .

  2. Does the physics of (Ga,Mn)N differ from (GaMn)As qualitatively or quantitatively? Is valance of Mn impurity 2+ or 3+?

    NASA Astrophysics Data System (ADS)

    Nelson, Ryky; Berlijn, Tom; Ku, Wei; Moreno, Juana; Jarrell, Mark

    2013-03-01

    (Ga,Mn)N is a promising material for spintronics due to its potential high currie temperature (Tc). However, unlike for (Ga,Mn)As, some of the experiments on (Ga,Mn)N are still controversial on the intrinsic nature of the magnetism. Furthermore, under debate are the spin and charge state of the disordered Mn impurities in (Ga,Mn)N and whether its local moments interact via the same exchange mechanism as in (Ga,Mn)As. To address these issues we will present ab-initio-based analyses of disorder and correlation via the recently developed Wannier function based methods.

  3. Low-temperature molar heat capacities and entropies of MnO2 (pyrolusite), Mn3O4 (hausmanite), and Mn2O3 (bixbyite)

    USGS Publications Warehouse

    Robie, R.A.; Hemingway, B.S.

    1985-01-01

    Pyrolusite (MnO2), hausmanite (Mn3O4), and bixbyite (Mn2O3), are important ore minerals of manganese and accurate values for their thermodynamic properties are desirable to understand better the {p(O2), T} conditions of their formation. To provide accurate values for the entropies of these important manganese minerals, we have measured their heat capacities between approximately 5 and 380 K using a fully automatic adiabatically-shielded calorimeter. All three minerals are paramagnetic above 100 K and become antiferromagnetic or ferrimagnetic at lower temperatures. This transition is expressed by a sharp ??-type anomaly in Cpmo for each compound with Ne??el temperatures TN of (92.2??0.2), (43.1??0.2), and (79.45??0.05) K for MnO2, Mn3O4, and Mn2O3, respectively. In addition, at T ??? 308 K, Mn2O3 undergoes a crystallographic transition, from orthorhombic (at low temperatures) to cubic. A significant thermal effect is associated with this change. Hausmanite is ferrimagnetic below TN and in addition to the normal ??-shape of the heat-capacity maxima in MnO2 and Mn2O3, it has a second rounded maximum at 40.5 K. The origin of this subsidiary bump in the heat capacity is unknown but may be related to a similar "anomalous bump" in the curve of magnetization against temperature at about 39 K observed by Dwight and Menyuk.(1) At 298.15 K the standard molar entropies of MnO2, Mn3O4, and Mn2O3, are (52.75??0.07), (164.1??0.2), and (113.7??0.2) J??K-1??mol-1, respectively. Our value for Mn3O4 is greater than that adopted in the National Bureau of Standards tables(2) by 14 per cent. ?? 1985.

  4. Does exposure to glyphosate lead to an increase in the micronuclei frequency? A systematic and meta-analytic review.

    PubMed

    Ghisi, Nédia de Castilhos; de Oliveira, Elton Celton; Prioli, Alberto José

    2016-02-01

    Glyphosate-based herbicides are among the most used pesticides worldwide. Reviews on the safety of glyphosate have been conducted by several regulatory agencies and researches centers, many times with contradictory results. This study is a systematic meta-analytical review of experimental studies on the relationship between exposure to the glyphosate (GLY) and its formulations with the formation of micronuclei (MN) to establish a quantitative estimate of the environmental risks. The natural logarithm (ln) of the estimated response ratio was calculated from 81 experiments. A meta-analysis was performed on the complete data set, and individual meta-analyses were conducted after stratification by test system, class of vertebrate, exposure route, gender, endpoints, type of literature, formulation, GLY dose and exposure time. A forest plot showed an overall positive association between GLY exposure and its formulations and MN, corroborated by the cumulative effects size. Different responses were observed on mammalian and non-mammalian. Interesting results was noticed in exposure route where oral administration of GLY presented no significance. Exposure by intraperitoneal injection presented the highest MN formation. Pure GLY caused fewer effects than to commercial mixtures, but both presented mutagenic effects. The studies with males presented significant responses, while studies with females were not significant. The cumulative effects size was not clearly related to GLY dose, and was negatively related to exposure time. It can be attributed to different test systems, exposure routes and protocols analyzed. In conclusion, our results support the hypothesis that exposure to GLY and its formulations increases the frequency of MN formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Nursing students' early exposure to clinical practice: an innovation in curriculum development.

    PubMed

    Hoyles, A; Pollard, C; Lees, S; Glossop, D

    2000-08-01

    This paper describes a pilot study addressing issues surrounding the balance and status given to both theory and practice in the foundation part of a pre-registration programme. Contemporary thinking seems to suggest that there is a need to reverse recent trends which have placed an emphasis on theory. To facilitate this a framework for clinical learning was adapted to guide students' early exposure to clinical practice. The focus was to develop the students' observational and reflective skills whilst also providing the students with a frame of reference within which they could explore their theoretical studies. The information and experiences gained as a result of this study have led to the integration of an Orientation Framework to support students' early clinical experiences in a pre-registration programme.

  6. Exposure to respirable dust and manganese and prevalence of airways symptoms, among Swedish mild steel welders in the manufacturing industry.

    PubMed

    Hedmer, Maria; Karlsson, Jan-Eric; Andersson, Ulla; Jacobsson, Helene; Nielsen, Jörn; Tinnerberg, Håkan

    2014-08-01

    Welding fume consists of metal fumes, e.g., manganese (Mn) and gases, e.g., ozone. Particles in the respirable dust (RD) size range dominate. Exposure to welding fume could cause short- and long-term respiratory effects. The prevalence of work-related symptoms among mild steel welders was studied, and the occupational exposure to welding fumes was quantified by repeated measurements of RD, respirable Mn, and ozone. Also the variance components were studied. A questionnaire concerning airway symptoms and occupational history was answered by 79% of a cohort of 484 welders. A group of welders (N = 108) were selected and surveyed by personal exposure measurements of RD and ozone three times during 1 year. The welders had a high frequency of work-related symptoms, e.g., stuffy nose (33%), ocular symptoms (28%), and dry cough (24%). The geometric mean exposure to RD and respirable Mn was 1.3 mg/m(3) (min-max 0.1-38.3 mg/m(3)) and 0.08 mg/m(3) (min-max <0.01-2.13 mg/m(3)), respectively. More than 50% of the Mn concentrations exceeded the Swedish occupational exposure limit (OEL). Mainly, low concentrations of ozone were measured, but 2% of the samples exceeded the OEL. Of the total variance for RD, 30 and 33% can be attributed to within-worker variability and between-company variability, respectively. Welders had a high prevalence of work-related symptom from the airways and eyes. The welders' exposure to Mn was unacceptably high. To reduce the exposure further, control measures in the welding workshops are needed. Correct use of general mechanical ventilation and local exhaust ventilation can, for example, efficiently reduce the exposure.

  7. Associations between prenatal and childhood PBDE exposure and early adolescent visual, verbal and working memory.

    PubMed

    Cowell, Whitney J; Margolis, Amy; Rauh, Virginia A; Sjödin, Andreas; Jones, Richard; Wang, Ya; Garcia, Wanda; Perera, Frederica; Wang, Shuang; Herbstman, Julie B

    2018-05-19

    Prenatal and childhood exposure to polybrominated diphenyl ether (PBDE) flame retardants has been inversely associated with cognitive performance, however, few studies have measured PBDE concentrations in samples collected during both prenatal and postnatal periods. We examined prenatal (cord) and childhood (ages 2, 3, 5, 7 and 9 years) plasma PBDE concentrations in relation to memory outcomes assessed between the ages of 9 and 14 years. The study sample includes a subset (n = 212) of the African American and Dominican children enrolled in the Columbia Center for Children's Environmental Health Mothers and Newborns birth cohort. We used multivariable linear regression to examine associations between continuous log 10 -transformed PBDE concentrations and performance on tests of visual, verbal and working memory in age-stratified models. We additionally used latent class growth analysis to estimate trajectories of exposure across early life, which we analyzed as a categorical variable in relation to memory outcomes. We examined interactions between PBDE exposure and sex using cross-product terms. Associations between prenatal exposure and working memory significantly varied by sex (p-interaction = 0.02), with inverse relations observed only among girls (i.e. β BDE-47  = -7.55, 95% CI: -13.84, -1.24). Children with sustained high concentrations of BDEs-47, 99 or 100 across childhood scored approximately 5-8 standard score points lower on tests of visual memory. Children with PBDE plasma concentrations that peaked during toddler years performed better on verbal domains, however, these associations were not statistically significant. Exposure to PBDEs during both prenatal and postnatal periods may disrupt memory domains in early adolescence. These findings contribute to a substantial body of evidence supporting the developmental neurotoxicity of PBDEs and underscore the need to reduce exposure among pregnant women and children. Copyright © 2018

  8. Intrinsic ferromagnetism in nanocrystalline Mn-doped ZnO depending on Mn concentration.

    PubMed

    Subramanian, Munisamy; Tanemura, Masaki; Hihara, Takehiko; Soga, Tetsuo; Jimbo, Takashi

    2011-04-01

    The physical properties of Zn(1-x)Mn(x)O nanoparticles synthesized by thermal decomposition are extensively investigated by X-ray diffraction (XRD), Transmission Electron Microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Raman light scattering and Hysteresis measurements. XRD and XPS spectra reveal the absence of secondary phase in nanocrystalline ZnO doped with 5% or less Mn; and, later confirms that the valance state of Mn to be 2+ for all the samples. Raman spectra exhibit a peak at 660 cm(-1) which we attribute to the intrinsic lattice defects of ZnO with increasing Mn concentration. Overall, our results demonstrate that ferromagnetic properties can be realized while Mn-doped ZnO obtained in the nanocrystalline form.

  9. Mn induced 1 × 2 reconstruction in the τ-MnAl(0 0 1) surface

    NASA Astrophysics Data System (ADS)

    Guerrero-Sánchez, J.; Takeuchi, Noboru

    2018-05-01

    We report on first principles total energy calculations to describe the structural, electronic and magnetic properties of MnAl(0 0 1) surfaces. We have concentrated in structural models having 1 × 1 and 1 × 2 periodicities, since recent experiments of the similar MnGa(0 0 1) surface have found 1 × 1 and 1 × 2 reconstructions. Our calculations show the existence of two stable structures for different ranges of chemical potential. A 1 × 1 surface is stable for Al-rich conditions, whereas a Mn-induced 1 × 2 reconstruction appears after increasing the Mn chemical potential up to Mn-rich conditions. It is important to notice that experimentally, Mn rich conditions are important for improved magnetic properties. The Mn layers in both structures have ferromagnetic arrangements, but they are aligned antiferromagnetically with the almost no magnetic Al atoms. Moreover, the on top Mn atoms, which produce the 1 × 2 reconstruction, align antiferromagnetically with the second layer Mn atoms. These findings are similar to those obtained experimentally in MnGa thin films grown by molecular beam epitaxy. Therefore, this method could also be used to grow the proposed MnAl films.

  10. Electrochemical performances of LiMnPO4 synthesized from non-stoichiometric Li/Mn ratio.

    PubMed

    Xiao, Jie; Chernova, Natasha A; Upreti, Shailesh; Chen, Xilin; Li, Zheng; Deng, Zhiqun; Choi, Daiwon; Xu, Wu; Nie, Zimin; Graff, Gordon L; Liu, Jun; Whittingham, M Stanley; Zhang, Ji-Guang

    2011-10-28

    In this paper, the influences of the lithium content in the starting materials on the final performances of as-prepared Li(x)MnPO(4) (x hereafter represents the starting Li content in the synthesis step which does not necessarily mean that Li(x)MnPO(4) is a single phase solid solution in this work.) are systematically investigated. It has been revealed that Mn(2)P(2)O(7) is the main impurity when Li < 1.0 while Li(3)PO(4) begins to form once x > 1.0. The interactions between Mn(2)P(2)O(7) or Li(3)PO(4) impurities and LiMnPO(4) are studied in terms of the structural, electrochemical, and magnetic properties. At a slow rate of C/50, the reversible capacity of both Li(0.5)MnPO(4) and Li(0.8)MnPO(4) increases with cycling. This indicates a gradual activation of more sites to accommodate a reversible diffusion of Li(+) ions that may be related to the interaction between Mn(2)P(2)O(7) and LiMnPO(4) nanoparticles. Among all of the different compositions, Li(1.1)MnPO(4) exhibits the most stable cycling ability probably because of the existence of a trace amount of Li(3)PO(4) impurity that functions as a solid-state electrolyte on the surface. The magnetic properties and X-ray absorption spectroscopy (XAS) of the MnPO(4)·H(2)O precursor, pure and carbon-coated Li(x)MnPO(4) are also investigated to identify the key steps involved in preparing a high-performance LiMnPO(4). This journal is © the Owner Societies 2011

  11. The Submillimeter Spectrum of MnH and MnD (X7Σ+)

    NASA Astrophysics Data System (ADS)

    Halfen, D. T.; Ziurys, L. M.

    2008-01-01

    The submillimeter-wave spectrum of the MnH and MnD radicals in their 7Σ+ ground states has been measured in the laboratory using direct absorption techniques. These species were created in the gas phase by the reaction of manganese vapor, produced in a Broida-type oven, with either H2 or D2 gas in the presence of a DC discharge. The N = 0 → 1 transition of MnH near 339 GHz was recorded, which consisted of multiple hyperfine components arising from both the manganese and hydrogen nuclear spins. The N = 2 → 3 transition of MnD near 517 GHz was measured as well, but in this case only the manganese hyperfine interactions were resolved. Both data sets were analyzed with a Hund's case b Hamiltonian, and rotational, fine structure, magnetic hyperfine, and electric quadrupole constants have been determined for the two manganese species. An examination of the magnetic hyperfine constants shows that MnH is primarily an ionic species, but has more covalent character than MnF. MnH is a good candidate species for astronomical searches with Herschel, particularly toward material associated with luminous blue variable stars.

  12. Longitudinal and contemporaneous manganese exposure in apartheid-era South Africa: Implications for the past and future.

    PubMed

    Hess, Catherine A; Smith, Martin J; Trueman, Clive; Schutkowski, Holger

    2015-03-01

    Manganese is a potent environmental toxin, with significant effects on human health. Manganese exposure is of particular concern in South Africa where in the last decade, lead in gasoline has been replaced by methylcyclopentadienyl manganese tricarbonyl (MMT). We investigated recent historical levels of manganese exposure in urban Gauteng, South Africa prior to the introduction of MMT in order to generate heretofore non-existent longitudinal public health data on manganese exposure in urban South Africans. Cortical bone manganese concentration was measured by inductively coupled plasma mass spectrometer in 211 deceased adults with skeletal material from a fully identified archived tissue collection at the University of Pretoria, South Africa. All tissues came from individuals who lived and died in urban Gauteng (Transvaal), between 1958 and 1998. Median Mn concentration within the sampled tissues was 0.3μgg -1 , which is within reported range for bone manganese concentration in non-occupationally exposed populations and significantly below that reported in individuals environmentally exposed to MMT. No significant differences were seen in bone Mn between men and women or in individuals of different ethnicity, which further suggests environmental, as opposed to occupational exposure. There were no significant temporal or geographic differences in bone Mn. The results suggest that Mn exposure was low and uniformly distributed across the whole population prior to the introduction of MMT as a gasoline additive. In addition, should manganese exposure follow the same patterns as vehicle-emitted lead, a clear pattern of exposure will emerge with individuals in the urban core facing the greatest manganese exposure. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1

    PubMed Central

    Bohu, Tsing; Santelli, Cara M.; Akob, Denise M.; Neu, Thomas R.; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

    2015-01-01

    Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling. PMID:26236307

  14. Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1

    USGS Publications Warehouse

    Bohu, Tsing; Santelli, Cara M; Akob, Denise M.; Neu, Thomas R; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

    2015-01-01

    Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling.

  15. Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1.

    PubMed

    Bohu, Tsing; Santelli, Cara M; Akob, Denise M; Neu, Thomas R; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

    2015-01-01

    Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling.

  16. Comparison of high MRI T1 signals with manganese concentration in brains of cynomolgus monkeys after 8 months of stainless steel welding-fume exposure.

    PubMed

    Park, Jung Duck; Chung, Yong Hyun; Kim, Choong Yong; Ha, Chang Soo; Yang, Seoung Oh; Khang, Hyun Soo; Yu, In Kyu; Cheong, Hae Kwan; Lee, Jong Seong; Song, Chang-Woo; Kwon, Il Hoon; Han, Jeong Hee; Sung, Jae Hyuck; Heo, Jeong Doo; Choi, Byung Sun; Im, Ruth; Jeong, Jayoung; Yu, Il Je

    2007-09-01

    Several pharmacokinetic studies on inhalation exposure to manganese (Mn) have already demonstrated that Mn readily accumulates in the olfactory and brain regions. However, a shortening of the magnetic resonance imaging (MRI) T1 relaxation time or high T1 signal intensity in specific sites of the brain, including the globus pallidus and subcortical frontal white matter, as indicative of tissue manganese accumulation has not yet been clearly established for certain durations of known doses of welding-fume exposure in experimental animals. Accordingly, to investigate the movement of manganese after welding-fume exposure, six cynomolgus monkeys were acclimated and assigned to three dose groups: unexposed, low dose (31 mg/m(3) total suspended particulate [TSP], 0.9 mg/m(3) of Mn), and high dose (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of total suspended particulate. The primates were exposed to manual metal arc stainless steel (MMA-SS) welding fumes for 2 h per day in an inhalation chamber system equipped with an automatic fume generator. Magnetic resonance imaging (MRI) studies were conducted before the initiation of exposure and thereafter every month. The tissue Mn concentrations were then measured after a plateau was reached regarding the shortening of the MRI T1 relaxation time. A dose-dependent increase in the Mn concentration was found in the lungs, while noticeable increases in the Mn concentrations were found in certain tissues, such as the liver, kidneys, and testes. Slight increases in the Mn concentrations were found in the caudate, putamen, frontal lobe, and substantia nigra, while a dose-dependent noticeable increase was only found in the globus pallidus. Therefore, the present results indicated that a shortening of the MRI T1 relaxation time corresponded well with the Mn concentration in the globus pallidus after prolonged welding-fume exposure.

  17. Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery

    PubMed Central

    Katusic, Slavica K.; Colligan, Robert C.; Wilder, Robert T.; Voigt, Robert G.; Olson, Michael D.; Sprung, Juraj; Weaver, Amy L.; Schroeder, Darrell R.; Warner, David O.

    2011-01-01

    BACKGROUND: Annually, millions of children are exposed to anesthetic agents that cause apoptotic neurodegeneration in immature animals. To explore the possible significance of these findings in children, we investigated the association between exposure to anesthesia and subsequent (1) learning disabilities (LDs), (2) receipt of an individualized education program for an emotional/behavior disorder (IEP-EBD), and (3) scores of group-administered achievement tests. METHODS: This was a matched cohort study in which children (N = 8548) born between January 1, 1976, and December 31, 1982, in Rochester, Minnesota, were the source of cases and controls. Those exposed to anesthesia (n = 350) before the age of 2 were matched to unexposed controls (n = 700) on the basis of known risk factors for LDs. Multivariable analysis adjusted for the burden of illness, and outcomes including LDs, receipt of an IEP-EBD, and the results of group-administered tests of cognition and achievement were outcomes. RESULTS: Exposure to multiple, but not single, anesthetic/surgery significantly increased the risk of developing LDs (hazard ratio: 2.12 [95% confidence interval: 1.26–3.54]), even when accounting for health status. A similar pattern was observed for decrements in group-administered tests of achievement and cognition. However, exposure did not affect the rate of children receiving an individualized education program. CONCLUSIONS: Repeated exposure to anesthesia and surgery before the age of 2 was a significant independent risk factor for the later development of LDs but not the need for educational interventions related to emotion/behavior. We cannot exclude the possibility that multiple exposures to anesthesia/surgery at an early age may adversely affect human neurodevelopment with lasting consequence. PMID:21969289

  18. Early genotoxic response and accumulation induced by waterborne copper, lead, and arsenic in European seabass, Dicentrarchus labrax.

    PubMed

    Canalejo, Antonio; Diaz-de-Alba, Margarita; Granado-Castro, M Dolores; Cordoba, Francisco; Espada-Bellido, Estrella; Galindo-Riaño, M Dolores; Torronteras, Rafael

    2016-02-01

    Cu, Pb, and As, which are among the most abundant metals in the aquatic environment, are also among the most health-threatened by causing diverse cellular injuries. The aim of this study was to assess and compare the potential early induction of genotoxic effects after waterborne Cu, Pb, and As exposure in European seabass, Dicentrarchus labrax, a commercial widely cultured fish, using the micronucleus (MN) assay in peripheral blood erythrocytes. Fish were exposed under laboratory conditions to nominal solutions ranging 0-10 mg/L for 24 and 96 h. Furthermore, actual metal ion concentrations were measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES) or differential pulse anodic stripping voltammetry (DPASV) in water and four fish tissues differentially related to environmental exposition and metal accumulation, i.e. the gills, liver, muscle, and brain. Dose-dependent increases of micronuclei (MNi) frequency were observed after these very short exposures; based on measured metal concentrations in water, the genotoxic effect ordered as Cu > As > Pb. Significant genotoxic effect at 0.009 mg/L Cu, 0.57 mg/L Pb, and 0.01 mg/L As was seen. For Cu and Pb these are only slightly higher, but for As it is notably lower than the USEPA criteria of maximum concentration to prevent acute toxicity in aquatic organisms. Furthermore, genotoxicity was differentially related to metal accumulation. MNi frequency correlated positively with the content of Pb in all the organs, with the content of As in liver and gills and only with the content of Cu in the brain. In conclusion, our findings raised environmental concerns because these depicted a genotoxic potential of Cu, Pb, and As after a very short exposure to low but environmentally relevant concentrations, too close to regulatory thresholds. In addition, the MN test in D. labrax could be considered an early biomarker of genotoxicity induced by these metals in fish.

  19. Manganese exposure from drinking water and children's academic achievement.

    PubMed

    Khan, Khalid; Wasserman, Gail A; Liu, Xinhua; Ahmed, Ershad; Parvez, Faruque; Slavkovich, Vesna; Levy, Diane; Mey, Jacob; van Geen, Alexander; Graziano, Joseph H; Factor-Litvak, Pam

    2012-01-01

    Drinking water manganese (WMn) is a potential threat to children's health due to its associations with a wide range of outcomes including cognitive, behavioral and neuropsychological effects. Although adverse effects of Mn on cognitive function of the children indicate possible impact on their academic achievement little evidence on this issue is available. Moreover, little is known regarding potential interactions between exposure to Mn and other metals, especially water arsenic (WAs). In Araihazar, a rural area of Bangladesh, we conducted a cross-sectional study of 840 children to investigate associations between WMn and WAs and academic achievement in mathematics and languages among elementary school-children, aged 8-11 years. Data on As and Mn exposure were collected from the participants at the baseline of an ongoing longitudinal study of school-based educational intervention. Annual scores of the study children in languages (Bangla and English) and mathematics were obtained from the academic achievement records of the elementary schools. WMn above the WHO standard of 400μg/L was associated with 6.4% score loss (95% CI=-12.3 to -0.5) in mathematics achievement test scores, adjusted for WAs and other sociodemographic variables. We did not find any statistically significant associations between WMn and academic achievement in either language. Neither WAs nor urinary As was significantly related to any of the three academic achievement scores. Our finding suggests that a large number of children in rural Bangladesh may experience deficits in mathematics due to high concentrations of Mn exposure in drinking water. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. High interpatient variability of treosulfan exposure is associated with early toxicity in paediatric HSCT: a prospective multicentre study.

    PubMed

    van der Stoep, M Y Eileen C; Bertaina, Alice; Ten Brink, Marloes H; Bredius, Robbert G; Smiers, Frans J; Wanders, Dominique C M; Moes, Dirk Jan A R; Locatelli, Franco; Guchelaar, Henk-Jan; Zwaveling, Juliëtte; Lankester, Arjan C

    2017-12-01

    Treosulfan-based conditioning is increasingly employed in paediatric haematopoietic stem cell transplantation (HSCT). Data on treosulfan pharmacokinetics in children are scarce, and the relationship between treosulfan exposure, toxicity and clinical outcome is unresolved. In this multicentre prospective observational study, we studied treosulfan pharmacokinetics and the drug's relationship with regimen-related toxicity and early clinical outcome in 77 paediatric patients. Treosulfan dose was 30 g/m 2 , administered over 3 consecutive days in infants <1 year old (n = 12) and 42 g/m 2 in children ≥1 year old (n = 65). Mean day 1 treosulfan exposure was 1744 ± 795 mg*h/l (10 g/m 2 ) and 1561 ± 511 mg*h/l (14 g/m 2 ), with an inter-individual variability of 56 and 33% in the respective groups. High treosulfan exposure (>1650 mg*h/l) was associated with an increased risk of mucosal [Odds ratio (OR) 4·40; 95% confidence interval (CI) 1·19-16·28, P = 0·026] and skin toxicity (OR 4·51; 95% CI 1·07-18·93, P = 0·040). No correlation was found between treosulfan exposure and the early clinical outcome parameters: engraftment, acute graft-versus-host disease and donor chimerism. Our study provides the first evidence in a large cohort of paediatric patients of high variability in treosulfan pharmacokinetics and an association between treosulfan exposure and early toxicity. Ongoing studies will reveal whether treosulfan exposure is related to long-term disease-specific outcome and late treatment-related toxicity. © 2017 John Wiley & Sons Ltd.

  1. Brain deposition and neurotoxicity of manganese in adult mice exposed via the drinking water

    PubMed Central

    Saritha, Krishna; Celia, Dodd A.; Shahryar, Hekmatyar K.; Nikolay, Filipov M.

    2013-01-01

    Natural leaching processes and/or anthropogenic contamination can result in ground water concentrations of the essential metal manganese (Mn) that far exceed the current regulatory standards. Neurological consequences of Mn drinking water (DW) overexposure to experimental animals, i.e. mice, including its brain deposition/distribution and behavioral effects are understudied. Adult male C57BL/6 mice were exposed to Mn via the DW for 8 weeks. After 5 weeks of Mn exposure, magnetic resonance imaging revealed significant Mn deposition in all examined brain regions; the degree of Mn deposition did not increase further a week later. Behaviorally, early hyperactivity and more time spent in the center of the arenas in an open field test, decreased forelimb grip strength and less time swimming in a forced swim test were observed after 6 weeks of Mn DW exposure. Eight-week Mn DW exposure did not alter striatal dopamine, its metabolites, or the expression of key dopamine homeostatic proteins, but it significantly increased striatal 5-hydroxyindoleacetic acid (a serotonin metabolite) level, without affecting the levels of serotonin itself. Increased expression (mRNA) of glial fibrillary acidic protein (GFAP, an astrocyte activation marker), heme oxygenase-1 and inducible nitric oxide synthase (oxidative and nitrosative stress markers, respectively) were observed 8 weeks post Mn DW exposure in the substantia nigra. Besides mRNA increases, GFAP protein expression was increased in the substantia nigra pars reticulata. In summary, the neurobehavioral deficits, characterized by locomotor and emotional perturbations, and nigral glial activation associated with significant brain Mn deposition are among the early signs of Mn neurotoxicity caused by DW overexposure. PMID:23832297

  2. Brain deposition and neurotoxicity of manganese in adult mice exposed via the drinking water.

    PubMed

    Krishna, Saritha; Dodd, Celia A; Hekmatyar, Shahryar K; Filipov, Nikolay M

    2014-01-01

    Natural leaching processes and/or anthropogenic contamination can result in ground water concentrations of the essential metal manganese (Mn) that far exceed the current regulatory standards. Neurological consequences of Mn drinking water (DW) overexposure to experimental animals, i.e., mice, including its brain deposition/distribution and behavioral effects are understudied. Adult male C57BL/6 mice were exposed to Mn via the DW for 8 weeks. After 5 weeks of Mn exposure, magnetic resonance imaging revealed significant Mn deposition in all examined brain regions; the degree of Mn deposition did not increase further a week later. Behaviorally, early hyperactivity and more time spent in the center of the arenas in an open field test, decreased forelimb grip strength and less time swimming in a forced swim test were observed after 6 weeks of Mn DW exposure. Eight-week Mn DW exposure did not alter striatal dopamine, its metabolites, or the expression of key dopamine homeostatic proteins, but it significantly increased striatal 5-hydroxyindoleacetic acid (a serotonin metabolite) levels, without affecting the levels of serotonin itself. Increased expression (mRNA) of glial fibrillary acidic protein (GFAP, an astrocyte activation marker), heme oxygenase-1 and inducible nitric oxide synthase (oxidative and nitrosative stress markers, respectively) were observed 8 weeks post-Mn DW exposure in the substantia nigra. Besides mRNA increases, GFAP protein expression was increased in the substantia nigra pars reticulata. In summary, the neurobehavioral deficits, characterized by locomotor and emotional perturbations, and nigral glial activation associated with significant brain Mn deposition are among the early signs of Mn neurotoxicity caused by DW overexposure.

  3. [Air pollutant exposure during pregnancy and fetal and early childhood development. Research protocol of the INMA (Childhood and Environment Project)].

    PubMed

    Esplugues, Ana; Fernández-Patier, Rosalía; Aguilera, Inma; Iñíguez, Carmen; García Dos Santos, Saúl; Aguirre Alfaro, Amelia; Lacasaña, Marina; Estarlich, Marisa; Grimalt, Joan O; Fernández, Marieta; Rebagliato, Marisa; Sala, María; Tardón, Adonina; Torrent, Maties; Martínez, María Dolores; Ribas-Fitó, Núria; Sunyer, Jordi; Ballester, Ferran

    2007-01-01

    The INMA (INfancia y Medio Ambiente [Spanish for Environment and Childhood]) project is a cooperative research network. This project aims to study the effects of environment and diet on fetal and early childhood development. This article aims to present the air pollutant exposure protocol during pregnancy and fetal and early childhood development of the INMA project. The information to assess air pollutant exposure during pregnancy is based on outdoor measurement of air pollutants (nitrogen dioxide [NO2], volatile organic compounds [VOC], ozone, particulate matter [PM10, PM2,5 ] and of their composition [polycyclic aromatic hydrocarbons]); measurement of indoor and personal exposure (VOC and NO2); urinary measurement of a biological marker of hydrocarbon exposure (1-hydroxypyrene); and data gathered by questionnaires and geographic information systems. These data allow individual air pollutant exposure indexes to be developed, which can then be used to analyze the possible effects of exposure on fetal development and child health. This protocol and the type of study allow an approximation to individual air pollutant exposure to be obtained. Finally, the large number of participants (N = 4,000), as well as their geographic and social diversity, increases the study's potential.

  4. Early-Life Antibiotic Exposure, Gut Microbiota Development, and Predisposition to Obesity.

    PubMed

    Azad, Meghan B; Moossavi, Shirin; Owora, Arthur; Sepehri, Shadi

    2017-01-01

    Antibiotics are often prescribed inappropriately to infants and young children, with potentially adverse effects on the developing gut microbiota and related metabolic processes. We review evidence from 17 epidemiologic studies suggesting that antibiotic exposure during critical periods of early development may influence weight gain and the development of obesity. Complementary research in both humans and rodents indicates that gut microbiota play a key role in this process, although further research is needed to confirm and characterize the causal mechanisms involved. Obesity is a complex and multifactorial condition; thus, a multipronged prevention strategy will be required to curb the current obesity epidemic. Evidence to date suggests this strategy should include the judicious use of antibiotics, especially in early life when the developing gut microbiota is particularly susceptible to perturbations with long-lasting implications for metabolic programming and obesity risk. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

  5. Synthesis and characterization of monomeric Mn (IV) and pseudo-tetrameric Mn (III) complexes: magnetic properties of Mn (III) complex.

    PubMed

    Yahsi, Yasemin; Kara, Hulya

    2014-06-05

    Two novel monomer Mn (IV) [Mn(3,5-ClL1)2]⋅(CH3OH), (1), [3,5-ClL1H2=N-(2-hydroxyethyl)-3,5-dichlorosalicylaldimine] (1) and hydrogen-bonded pseudo-tetramer Mn (III) [Mn(5-BrL2)(H2O)2]2⋅[Mn(5-BrL2)(H2O)]2⋅2⋅(ClO4), (2), [5-BrL2H2=N,N'-bis(5-bromosalicylidenato)-1,2-diamino-2-methylpropane)] (2) Schiff base complexes have been synthesized and their crystal structures have been determined by single crystal X-ray diffraction analysis. A variable temperature magnetic susceptibility measurement study has been performed for complex (2) and the result indicates there is a very weak antiferromagnetic interaction (J=-0.40±0.016cm(-1)) between the two manganese (III) centers. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Cumulative Effects of Prenatal Substance Exposure and Early Adversity on Foster Children's HPA-Axis Reactivity during a Psychosocial Stressor

    ERIC Educational Resources Information Center

    Fisher, Philip A.; Kim, Hyoun K.; Bruce, Jacqueline; Pears, Katherine C.

    2012-01-01

    Dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis stress response has been reported among individuals with prenatal substance exposure and those with early adversity exposure. However, few researchers have examined the combined effects of these risk factors. Patterns of HPA reactivity among maltreated foster children with and without…

  7. Chondritic Mn/Na ratio and limited post-nebular volatile loss of the Earth

    NASA Astrophysics Data System (ADS)

    Siebert, Julien; Sossi, Paolo A.; Blanchard, Ingrid; Mahan, Brandon; Badro, James; Moynier, Frédéric

    2018-03-01

    The depletion pattern of volatile elements on Earth and other differentiated terrestrial bodies provides a unique insight as to the nature and origin of planetary building blocks. The processes responsible for the depletion of volatile elements range from the early incomplete condensation in the solar nebula to the late de-volatilization induced by heating and impacting during planetary accretion after the dispersion of the H2-rich nebular gas. Furthermore, as many volatile elements are also siderophile (metal-loving), it is often difficult to deconvolve the effect of volatility from core formation. With the notable exception of the Earth, all the differentiated terrestrial bodies for which we have samples have non-chondritic Mn/Na ratios, taken as a signature of post-nebular volatilization. The bulk silicate Earth (BSE) is unique in that its Mn/Na ratio is chondritic, which points to a nebular origin for the depletion; unless the Mn/Na in the BSE is not that of the bulk Earth (BE), and has been affected by core formation through the partitioning of Mn in Earth's core. Here we quantify the metal-silicate partitioning behavior of Mn at deep magma ocean pressure and temperature conditions directly applicable to core formation. The experiments show that Mn becomes more siderophile with increasing pressure and temperature. Modeling the partitioning of Mn during core formation by combining our results with previous data at lower P-T conditions, we show that the core likely contains a significant fraction (20 to 35%) of Earth's Mn budget. However, we show that the derived Mn/Na value of the bulk Earth still lies on the volatile-depleted end of a trend defined by chondritic meteorites in a Mn/Na vs Mn/Mg plot, which tend to higher Mn/Na with increasing volatile depletion. This suggests that the material that formed the Earth recorded similar chemical fractionation processes for moderately volatile elements as chondrites in the solar nebula, and experienced limited post

  8. Tough cryogenic alloys from the Fe-Mn and Fe-Mn-Cr systems

    NASA Technical Reports Server (NTRS)

    Schanfein, M. J.; Zackay, V. F.; Morris, J. W., Jr.

    1974-01-01

    By adjusting composition, metastable gamma (austenite) and epsilon (hexagonal) martensite may be retained in Fe-Mn and Fe-Mn-Cr alloys and used to impact toughness through the TRIP mechanism. The resulting alloys have excellent toughness at cryogenic temperatures. The best alloys obtained to date are: Fe-20Mn, with sigma (sub y) = 79ksi and K sub IC = 275ksi square root of (in) at 77 K, and Fc-16Mn-8Cr, with sigma sub y = 85ksi and K sub IC = 72ksi square root of (in) at 77 K.

  9. Impact of ferromanganese alloy plants on household dust manganese levels: implications for childhood exposure.

    PubMed

    Lucas, E L; Bertrand, P; Guazzetti, S; Donna, F; Peli, M; Jursa, T P; Lucchini, R; Smith, D R

    2015-04-01

    Adolescents living in communities with ferromanganese alloy plant activity have been shown to exhibit deficits in olfactory and fine motor function. Household dust may serve as an important manganese (Mn) exposure pathway to children, though dust Mn concentrations have not previously been measured to assess household contamination from ferromanganese alloy plant emissions. Here we determined the association between dust concentrations and surface loadings of Mn and other metals (Al, Cd, Cr, Cu, Fe, Pb, and Zn) in indoor and outdoor household dust from three Italian communities that differ by history of ferromanganese alloy plant activity: Bagnolo Mella, with an active ferromanganese alloy plant (n=178 households); Valcamonica, with historically active plants (n=166); and Garda Lake, with no history of ferromanganese plant activity (n=99). We also evaluated Mn levels in other environmental (soil, airborne particulates) and candidate biomarker (blood, hair, saliva, fingernails) samples from children within the households. Household dust Mn concentrations and surface loadings were significantly different between the three sites, with levels highest in Bagnolo Mella (outdoor median Mn concentration=4620, range 487-183,000µg/g), intermediate in Valcamonica (median=876, range 407-8240µg/g), and lowest in Garda Lake (median=407, range 258-7240µg/g). Outdoor dust Mn concentrations in Bagnolo Mella, but not the other communities, were significantly inversely related with distance from the plant (R(2)=0.6630, P<0.0001). Moreover, outdoor dust Mn concentrations and loadings were highly predictive of but significantly higher than indoor dust Mn concentrations and loadings by ~2 to ~7-fold (Mn concentrations) and ~7 to ~20-fold (Mn loadings). Finally, both indoor and outdoor dust Mn concentrations and outdoor dust Mn loading values were highly significantly correlated with both soil and air Mn concentrations, and with children's hair and fingernail Mn concentrations, but

  10. Impact of Ferromanganese Alloy Plants on Household Dust Manganese Levels: Implications for Childhood Exposure

    PubMed Central

    Lucas, E.L.; Bertrand, P.; Guazzetti, S.; Donna, F.; Peli, M.; Jursa, T.R.; Lucchini, R.; Smith, D.R.

    2015-01-01

    Adolescents living in communities with ferromanganese alloy plant activity have been shown to exhibit deficits in olfactory and fine motor function. Household dust may serve as an important manganese (Mn) exposure pathway to children, though dust Mn concentrations have not previously been measured to assess household contamination from ferromanganese alloy plant emissions. Here we determined the association between dust concentrations and surface loadings of Mn and other metals (Al, Cd, Cr, Cu, Fe, Pb, and Zn) in indoor and outdoor household dust from three Italian communities that differ by history of ferromanganese alloy plant activity: Bagnolo Mella, with an active ferromanganese alloy plant (n=178 households); Valcamonica, with historically active plants (n=166); and Garda Lake, with no history of ferromanganese plant activity (n=99). We also evaluated Mn levels in other environmental (soil, airborne particulates) and candidate biomarker (blood, hair, saliva, fingernails) samples from children within the households. Household dust Mn concentrations and surface loadings were significantly different between the three sites, with levels highest in Bagnolo Mella (outdoor median Mn concentration = 4620, range 487 – 183,000 µg/g), intermediate in Valcamonica (median = 876, range 407 – 8240 µg/g), and lowest in Garda Lake (median = 407, range 258 – 7240 µg/g). Outdoor dust Mn concentrations in Bagnolo Mella, but not the other communities, were significantly inversely related with distance from the plant (R2=0.6630, P<0.0001). Moreover, outdoor dust Mn concentrations and loadings were highly predictive of but significantly higher than indoor dust Mn concentrations and loadings by ~2 to ~7-fold (Mn concentrations) and ~7 to ~20-fold (Mn loadings). Finally, both indoor and outdoor dust Mn concentrations and outdoor dust Mn loading values were highly significantly correlated with both soil and air Mn concentrations, and with children’s hair and fingernail Mn

  11. Childhood Exposure to Adversity and Risk of Substance-Use Disorder in Two American Indian Populations: The Meditational Role of Early Substance-Use Initiation*

    PubMed Central

    Whitesell, Nancy Rumbaugh; Beals, Janette; Mitchell, Christina M.; Manson, Spero M.; Turner, R. Jay

    2009-01-01

    Objective: We examined the relationship of childhood exposure to adversity and risk of substance-use disorder in two culturally distinct American Indian reservation communities, exploring both the role of early initiation of substance use in mediating this relationship and variation in risk across types of adversity exposure. Method: The American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project provided data from 2,927 American Indians on the occurrence and age at onset of adversities, substance use, and substance-use-disorder symptoms. Results: The risk of substance-use disorder associated with early adversity was explained partially by early initiation of substance use. Three types of adversity (major childhood events, traumas, and witnessed violence) were associated with early onset of substance use and increased risk of substance-use disorder. Gender and tribe were also related to variation in both early substance use and substance-use disorder. Conclusions: Early exposure to adverse events was associated with early substance use and the subsequent development of substance-use disorders among American Indians. Public health initiatives targeting substance use and substance-use disorders in American Indian communities should include efforts to help children in these communities cope with adversities they encounter. PMID:19895776

  12. Cognitive Function Related to Environmental Exposure to ...

    EPA Pesticide Factsheets

    Background: The towns of Marietta and East Liverpool (EL), Ohio, have been identified as having elevated manganese (Mn) in air due to industrial pollution. Objectives: To evaluate relationships between environmental Mn (Mn-air) exposure and distance from the source and cognitive function in residents of two Ohio towns. Methods: Data were obtained from an EPA-sponsored study comparing two towns exposed to Mn-air (Marietta and EL). A cross-sectional design was used. The same inclusion/exclusion criteria and procedures were applied in the two towns. A neuropsychological screening test battery was administered to study participants (EL=86, Marietta=100) which included Stroop Color Word Test, Animal Naming, Auditory Consonant Trigrams (ACT) and Rey-O. To estimate Mn-air, U.S.EPA’s AERMOD dispersion model was used. Distance from source was calculated based on participants’ residential address and air miles from industrial facility emitting Mn-air. A binary logistic regression model controlling for annual household income was used to examine distance from source and neuropsychological outcomes Results: There were no age, sex, or employment status differences between the two towns. Years education was lower in EL (mean (M)=12.9) than Marietta (M=14.6) and years residency in town were higher in EL (M=47.0) than Marietta (M=36.1). EL participants resided closer to the Mn source than Marietta (M=1.12 vs M=4.75 air miles). Mn-air concentrations were higher in EL (M=0

  13. Enstatite Meteorites and the Original Heterogeneity of Mn-53 Distribution in the Solar Nebula

    NASA Technical Reports Server (NTRS)

    Lugmair, Guenter W.

    1999-01-01

    We have shown earlier that the relative abundance of radiogenic Cr-53 in bulk ordinary chondrites (approximately 0.48 epsilon) is clearly different from that in the earth-moon system (0 epsilon). The SNC parent body (Mars) is characterized by an intermediate Cr-53 excess (approximately 0.23 epsilon). We have also shown that the Mn-Cr systematics of the howardite-eucrite-diogenite parent body (HED PB, the asteroid Vesta) is consistent with the chondritic Mn/Cr ratio in the bulk HED PB and that it has a Cr-53 excess of approximately 0.5 epsilon units which is within error the same as that of chondrites. It appears that the excesses of Cr-53 in these planets are a function of their present heliocentric distance. The study of some other meteorite classes (angrites, pallasites, primitive achondrites) has shown that their Mn-CR systematics is consistent with that of the ordinary chondrites. The observed gradient in the radiogenic Cr-53 abundances can be explained by a). an early volatility controlled radial Mn/Cr fractionation in the nebula or b). an original heterogeneity of Mn-53. The first assumption, however, requires the Mn/Cr ratios of the bulk Earth and Mars to be considerably lower than the inferred model Mn/Cr ratios for these two planets. For this reason, we suggested that the observed gradient is due to an original radial Mn-53 heterogeneity in the late nebula.

  14. Systemic immune cell response in rats after pulmonary exposure to manganese-containing particles collected from welding aerosols.

    PubMed

    Antonini, James M; Zeidler-Erdely, Patti C; Young, Shih-Houng; Roberts, Jenny R; Erdely, Aaron

    2012-01-01

    Welding fume inhalation affects the immune system of exposed workers. Manganese (Mn) in welding fume may induce immunosuppressive effects. The goal was to determine if Mn in welding fume alters immunity by reducing the number of circulating total leukocytes and specific leukocyte sub-populations. Sprague-Dawley rats were treated by intratracheal instillation (ITI) with either a single dose (2.00 mg/rat) or repeated doses (0.125 or 2.00 mg/rat for 7 weeks) with welding fumes that contained different levels of Mn. Additional rats were treated by ITI once a week for 7 weeks with the two doses of manganese chloride (MnCl₂). Bronchoalveolar lavage was performed to assess lung inflammation. Also, whole blood was recovered, and the number of circulating total leukocytes, as well as specific lymphocyte subsets, was determined by flow cytometry. The welding fume highest in Mn content significantly increased lung inflammation, injury, and production of inflammatory cytokines and chemokines compared to all other treatment groups. In addition, the same group expressed significant decreases in the number of circulating CD4⁺ and CD8⁺ T-lymphocytes after a single exposure, and significant reductions in the number of circulating total lymphocytes, primarily CD4⁺ and CD8⁺ T-lymphocytes, after repeated exposures (compared to control values). Repeated MnCl₂ exposure led to a trend of a reduction (but not statistically significant) in circulating total lymphocytes, attributable to the changes in the CD4⁺ T-lymphocyte population levels. The welding fume with the lower concentration of Mn had no significant effect on the numbers of blood lymphocytes and lymphocyte subsets compared to control values. Evidence from this study indicates that pulmonary exposure to certain welding fumes cause decrements in systemic immune cell populations, specifically circulating T-lymphocytes, and these alterations in immune cell number are not dependent exclusively on Mn, but likely a

  15. Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure.

    PubMed

    Raineki, Charlis; Bodnar, Tamara S; Holman, Parker J; Baglot, Samantha L; Lan, Ni; Weinberg, Joanne

    2017-11-01

    The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8-12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Prenatal and Early Postnatal Exposure to Cigarette Smoke Decreases BDNF/TrkB Signaling and Increases Abnormal Behaviors Later in Life

    PubMed Central

    Xiao, Lan; Kish, Vincent L.; Benders, Katherine M.

    2016-01-01

    Background: Cigarette smoke exposure during prenatal and early postnatal periods increases the incidence of a variety of abnormal behaviors later in life. The purpose of this study was to identify the possible critical period of susceptibility to cigarette smoke exposure and evaluate the possibe effects of cigarette smoke during early life on brain-derived neurotrophic factor/neurotrophic tyrosine kinase receptor B signaling in the brain. Methods: Three different age of imprinting control region mice were exposed to cigarette smoke or filtered air for 10 consecutive days beginning on either gestational day 7 by maternal exposure, or postnatal days 2 or 21 by direct inhalation. A series of behavioral profiles and neurotrophins in brain were measured 24 hours after mice received acute restraint stress for 1 hour on postnatal day 59. Results: Cigarette smoke exposure in gestational day 7 and postnatal day 2 produced depression-like behaviors as evidenced by significantly increased immobility in both tail suspension and forced-swim test. Increased entry latencies, but not ambulation in the open field test, were also observed in the gestational day 7 and postnatal day 2 cigarette smoke exposure groups. Genetic analysis showed that gestational day 7 cigarette smoke exposure significantly altered mRNA level of brain-derived neurotrophic factor/tyrosine kinase receptor B in the hippocampus. However, behavioral profiles and brain-derived neurotrophic factor/tyrosine kinase receptor B signaling were not significantly changed in PND21 cigarette smoke exposure group compared with FA group. Conclusions: These results suggest that a critical period of susceptibility to cigarette smoke exposure exists in the prenatal and early postnatal period, which results a downregulation in brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in the hippocampus and enhances depression-like behaviors later in life. PMID:26503133

  17. High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Steinmaus, Craig, E-mail: craigs@berkeley.edu

    Background: Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods: We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤ 10 μg/L. Results: Compared to adults never exposed > 10 μg/L, adults born in Antofagasta during the high exposuremore » period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 mL decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 mL). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions: Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. - Highlights: • Based on its unique geology, lifetime arsenic exposure can be assessed in north Chile. • Signs and symptoms of lung disease were associated with early-life arsenic exposure. • Evidence of lung disease was also associated with moderate arsenic exposure.« less

  18. Enhanced Cycleability of Amorphous MnO₂ by Covering on α-MnO₂ Needles in an Electrochemical Capacitor.

    PubMed

    Liu, Quanbing; Ji, Shan; Yang, Juan; Wang, Hui; Pollet, Bruno G; Wang, Rongfang

    2017-08-24

    An allomorph MnO₂@MnO₂ core-shell nanostructure was developed via a two-step aqueous reaction method. The data analysis of Scanning Electron Microscopy, Transmission Electron Microscopy, X-Ray Diffraction and N₂ adsorption-desorption isotherms experiments indicated that this unique architecture consisted of a porous layer of amorphous-MnO₂ nano-sheets which were well grown onto the surface of α-MnO₂ nano-needles. Cyclic voltammetry experiments revealed that the double-layer charging and Faradaic pseudo -capacity of the MnO₂@MnO₂ capacitor electrode contributed to a specific capacitance of 150.3 F·g -1 at a current density of 0.1 A·g -1 . Long cycle life experiments on the as-prepared MnO₂@MnO₂ sample showed nearly a 99.3% retention after 5000 cycles at a current density of 2 A·g -1 . This retention value was found to be significantly higher than those reported for amorphous MnO₂-based capacitor electrodes. It was also found that the remarkable cycleability of the MnO₂@MnO₂ was due to the supporting role of α-MnO₂ nano-needle core and the outer amorphous MnO₂ layer.

  19. Spin reorientation and Ce-Mn coupling in antiferromagnetic oxypnictide CeMnAsO

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Qiang; Tian, Wei; Peterson, Spencer G.

    2015-02-18

    Structure and magnetic properties of high-quality polycrystlline CeMnAsO, a parent compound of the “1111”-type oxypnictides, have been investigated using neutron powder diffraction and magnetization measurements. We find that CeMnAsO undergoes a C-type antiferromagnetic order with Mn 2+(S = 5/2) moments pointing along the c axis below a relatively high Néel temperature of T N = 347(1) K. Below T SR = 35 K, two simultaneous transitions occur where the Mn moments reorient from the c axis to the ab plane preserving the C-type magnetic order, and Ce moments undergo long-range AFM ordering with antiparallel moments pointing in the ab plane.more » Another transition to a noncollinear magnetic structure occurs below 7 K. The ordered moments of Mn and Ce at 2 K are 3.32(4) μ B and 0.81(4)μ B, respectively. We find that CeMnAsO primarily falls into the category of a local-moment antiferromagnetic insulator in which the nearest-neighbor interaction (J 1) is dominant with J 2 < J 1/2 in the context of J 1 – J 2 – J c model. The spin reorientation transition driven by the coupling between Ce and the transition metal seems to be common to Mn, Fe, and Cr ions, but not to Co and Ni ions in the isostructural oxypnictides. As a result, a schematic illustration of magnetic structures in Mn and Ce sublattices in CeMnAsO is presented.« less

  20. Structure-electrochemical evolution of a Mn-rich P2 Na 2/3Fe 0.2Mn 0.8O 2 Na-ion battery cathode

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dose, Wesley M.; Sharma, Neeraj; Pramudita, James C.

    The structural evolution of electrode materials directly influences the performance of sodium-ion batteries. In this work, in situ synchrotron X-ray diffraction is used to investigate the evolution of the crystal structure of a Mn-rich P2-phase Na 2/3Fe 0.2Mn 0.8O 2 cathode. A single-phase reaction takes place for the majority of the discharge–charge cycle at ~C/10, with only a short, subtle hexagonal P2 to hexagonal P2 two-phase region early in the first charge. Thus, a higher fraction of Mn compared to previous studies is demonstrated to stabilize the P2 structure at high and low potentials, with neither “Z”/OP4 phases in themore » charged state nor significant quantities of the P'2 phase in the discharged state between 1.5 and 4.2 V. Notably, sodium ions inserted during discharge are located on both available crystallographic sites, albeit with a preference for the site sharing edges with the MO 6 octahedral unit. The composition Na ~0.70Fe 0.2Mn 0.8O 2 prompts a reversible single-phase sodium redistribution between the two sites. Sodium ions vacate the site sharing faces (Naf), favoring the site sharing edges (Nae) to give a Nae/Naf site occupation of 4:1 in the discharged state. This site preference could be an intermediate state prior to the formation of the P'2 phase. Furthermore, this work shows how the Mn-rich Na 2/3Fe 0.2Mn 0.8O 2 composition and its sodium-ion distribution can minimize phase transitions during battery function, especially in the discharged state.« less

  1. Structure-electrochemical evolution of a Mn-rich P2 Na 2/3Fe 0.2Mn 0.8O 2 Na-ion battery cathode

    DOE PAGES

    Dose, Wesley M.; Sharma, Neeraj; Pramudita, James C.; ...

    2017-08-04

    The structural evolution of electrode materials directly influences the performance of sodium-ion batteries. In this work, in situ synchrotron X-ray diffraction is used to investigate the evolution of the crystal structure of a Mn-rich P2-phase Na 2/3Fe 0.2Mn 0.8O 2 cathode. A single-phase reaction takes place for the majority of the discharge–charge cycle at ~C/10, with only a short, subtle hexagonal P2 to hexagonal P2 two-phase region early in the first charge. Thus, a higher fraction of Mn compared to previous studies is demonstrated to stabilize the P2 structure at high and low potentials, with neither “Z”/OP4 phases in themore » charged state nor significant quantities of the P'2 phase in the discharged state between 1.5 and 4.2 V. Notably, sodium ions inserted during discharge are located on both available crystallographic sites, albeit with a preference for the site sharing edges with the MO 6 octahedral unit. The composition Na ~0.70Fe 0.2Mn 0.8O 2 prompts a reversible single-phase sodium redistribution between the two sites. Sodium ions vacate the site sharing faces (Naf), favoring the site sharing edges (Nae) to give a Nae/Naf site occupation of 4:1 in the discharged state. This site preference could be an intermediate state prior to the formation of the P'2 phase. Furthermore, this work shows how the Mn-rich Na 2/3Fe 0.2Mn 0.8O 2 composition and its sodium-ion distribution can minimize phase transitions during battery function, especially in the discharged state.« less

  2. Electrochemical trapping of metastable Mn3+ ions for activation of MnO2 oxygen evolution catalysts.

    PubMed

    Morgan Chan, Zamyla; Kitchaev, Daniil A; Nelson Weker, Johanna; Schnedermann, Christoph; Lim, Kipil; Ceder, Gerbrand; Tumas, William; Toney, Michael F; Nocera, Daniel G

    2018-06-05

    Electrodeposited manganese oxide films are promising catalysts for promoting the oxygen evolution reaction (OER), especially in acidic solutions. The activity of these catalysts is known to be enhanced by the introduction of Mn 3+ We present in situ electrochemical and X-ray absorption spectroscopic studies, which reveal that Mn 3+ may be introduced into MnO 2 by an electrochemically induced comproportionation reaction with Mn 2+ and that Mn 3+ persists in OER active films. Extended X-ray absorption fine structure (EXAFS) spectra of the Mn 3+ -activated films indicate a decrease in the Mn-O coordination number, and Raman microspectroscopy reveals the presence of distorted Mn-O environments. Computational studies show that Mn 3+ is kinetically trapped in tetrahedral sites and in a fully oxidized structure, consistent with the reduction of coordination number observed in EXAFS. Although in a reduced state, computation shows that Mn 3+ states are stabilized relative to those of oxygen and that the highest occupied molecular orbital (HOMO) is thus dominated by oxygen states. Furthermore, the Mn 3+ (T d ) induces local strain on the oxide sublattice as observed in Raman spectra and results in a reduced gap between the HOMO and the lowest unoccupied molecular orbital (LUMO). The confluence of a reduced HOMO-LUMO gap and oxygen-based HOMO results in the facilitation of OER on the application of anodic potentials to the δ-MnO 2 polymorph incorporating Mn 3+ ions.

  3. Electrochemical Trapping of Metastable Mn3+ Ions for Activation of MnO2 Oxygen Evolution Catalysts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tumas, William; Chan, Zamyla Morgan; Kitchaev, Daniil A.

    Electrodeposited manganese oxide films are promising catalysts for promoting the oxygen evolution reaction (OER), especially in acidic solutions. The activity of these catalysts is known to be enhanced by the introduction of Mn3+. We present in situ electrochemical and X-ray absorption spectroscopic studies, which reveal that Mn3+ may be introduced into MnO2 by an electrochemically induced comproportionation reaction with Mn2+ and that Mn3+ persists in OER active films. Extended X-ray absorption fine structure (EXAFS) spectra of the Mn3+-activated films indicate a decrease in the Mn-O coordination number, and Raman microspectroscopy reveals the presence of distorted Mn-O environments. Computational studies showmore » that Mn3+ is kinetically trapped in tetrahedral sites and in a fully oxidized structure, consistent with the reduction of coordination number observed in EXAFS. Although in a reduced state, computation shows that Mn3+ states are stabilized relative to those of oxygen and that the highest occupied molecular orbital (HOMO) is thus dominated by oxygen states. Furthermore, the Mn3+(Td) induces local strain on the oxide sublattice as observed in Raman spectra and results in a reduced gap between the HOMO and the lowest unoccupied molecular orbital (LUMO). The confluence of a reduced HOMO-LUMO gap and oxygen-based HOMO results in the facilitation of OER on the application of anodic potentials to the d-MnO2 polymorph incorporating Mn3+ ions.« less

  4. Maternal Exposure to Occupational Asthmagens During Pregnancy and Autism Spectrum Disorder in the Study to Explore Early Development.

    PubMed

    Singer, Alison B; Windham, Gayle C; Croen, Lisa A; Daniels, Julie L; Lee, Brian K; Qian, Yinge; Schendel, Diana E; Fallin, M Daniele; Burstyn, Igor

    2016-11-01

    Maternal immune activity has been linked to children with autism spectrum disorder (ASD). We examined maternal occupational exposure to asthma-causing agents during pregnancy in relation to ASD risk. Our sample included 463 ASD cases and 710 general population controls from the Study to Explore Early Development whose mothers reported at least one job during pregnancy. Asthmagen exposure was estimated from a published job-exposure matrix. The adjusted odds ratio for ASD comparing asthmagen-exposed to unexposed was 1.39 (95 % CI 0.96-2.02). Maternal workplace asthmagen exposure was not associated with ASD risk in this study, but this result does not exclude some involvement of maternal exposure to asthma-causing agents in ASD.

  5. Manganese Exposure from Drinking Water and Children’s Classroom Behavior in Bangladesh

    PubMed Central

    Khan, Khalid; Factor-Litvak, Pam; Wasserman, Gail A.; Liu, Xinhua; Ahmed, Ershad; Parvez, Faruque; Slavkovich, Vesna; Levy, Diane; Mey, Jacob; van Geen, Alexander

    2011-01-01

    Background: Evidence of neurological, cognitive, and neuropsychological effects of manganese (Mn) exposure from drinking water (WMn) in children has generated widespread public health concern. At elevated exposures, Mn has been associated with increased levels of externalizing behaviors, including irritability, aggression, and impulsivity. Little is known about potential effects at lower exposures, especially in children. Moreover, little is known regarding potential interactions between exposure to Mn and other metals, especially arsenic (As). Objectives: We conducted a cross-sectional study of 201 children to investigate associations of Mn and As in tube well water with classroom behavior among elementary school children, 8–11 years of age, in Araihazar, Bangladesh. Methods: Data on exposures and behavioral outcomes were collected from the participants at the baseline of an ongoing longitudinal study of child intelligence. Study children were rated by their school teachers on externalizing and internalizing items of classroom behavior using the standardized Child Behavior Checklist-Teacher’s Report Form (CBCL-TRF). Results: Log-transformed WMn was positively and significantly associated with TRF internalizing [estimated β = 0.82; 95% confidence interval (CI), 0.08–1.56; p = 0.03], TRF externalizing (estimated β = 2.59; 95% CI, 0.81–4.37; p =0.004), and TRF total scores (estimated β = 3.35; 95% CI, 0.86–5.83; p = 0.008) in models that adjusted for log-transformed water arsenic (WAs) and sociodemographic covariates. We also observed a positive monotonic dose–response relationship between WMn and TRF externalizing and TRF total scores among the participants of the study. We did not find any significant associations between WAs and various scales of TRF scores. Conclusion: These observations reinforce the growing concern regarding the neurotoxicologic effects of WMn in children. PMID:21493178

  6. Early-Life Phthalate Exposure and Adiposity at 8 Years of Age.

    PubMed

    Shoaff, Jessica; Papandonatos, George D; Calafat, Antonia M; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P; Yolton, Kimberly; Braun, Joseph M

    2017-09-11

    Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022.

  7. Early-Life Phthalate Exposure and Adiposity at 8 Years of Age

    PubMed Central

    Papandonatos, George D.; Calafat, Antonia M.; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P.; Yolton, Kimberly; Braun, Joseph M.

    2017-01-01

    Background: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother–child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1–8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate–adiposity associations at each visit, test differences in phthalate–adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): −4.8, −0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022 PMID:28935615

  8. Prolactin is a peripheral marker of manganese neurotoxicity

    PubMed Central

    Marreilha dos Santos, AP; Lopes Santos, M; BatorÉu, Maria C; Aschner, M

    2011-01-01

    Excessive exposure to Mn induces neurotoxicity, referred to as manganism. Exposure assessment relies on Mn blood and urine analyses, both of which show poor correlation to exposure. Accordingly, there is a critical need for better surrogate biomarkers of Mn exposure. The aim of this study was to examine the relationship between Mn exposure and early indicators of neurotoxicity, with particular emphasis on peripheral biomarkers. Male Wistar rats (180–200 g) were injected intraperitoneally with 4 or 8 doses of Mn (10 mg/kg). Mn exposure was evaluated by analysis of Mn levels in brain and blood along with biochemical end-points (see below). Results Brain Mn levels were significantly increased both after 4 and 8 doses of Mn compared with controls (p<0.001). Blood levels failed to reflect a dose-dependent increase in brain Mn, with only the 8-dose treated group showing significant differences (p<0.001). Brain glutathione (GSH) levels were significantly decreased in the 8-dose-treated animals (p<0.001). A significant and dose-dependent increase in prolactin levels was found for both treated groups (p<0.001) compared to controls. In addition, a decrease in motor activity was observed in the 8-dose-treated group compared to controls. Conclusions 1) The present study demonstrates that peripheral blood level is a poor indicator of Mn brain accumulation and exposure; 2) Mn reduces GSH brain levels, likely reflecting oxidative stress; 3) Mn increases blood prolactin levels, indicating changes in the integrity of the dopaminergic system. Taken together these results suggest that peripheral prolactin levels may serve as reliable predictive biomarkers of Mn neurotoxicity. PMID:21262206

  9. Magnetic phase change in Mn-doped ZnSnAs2 thin films depending on Mn concentration

    NASA Astrophysics Data System (ADS)

    Uchitomi, Naotaka; Hidaka, Shiro; Saito, Shin; Asubar, Joel T.; Toyota, Hideyuki

    2018-04-01

    The relationship between Mn concentration and Curie temperature (TC) is studied for Mn-doped ZnSnAs2 ferromagnetic semiconductors, epitaxially grown on InP substrates by molecular beam epitaxy. In the ferromagnetic phase, Mn distributions in a (Zn,Mn,Sn)As2 thin film with 7.2 cation percent (cat. %) Mn are investigated using three-dimensional atom probe tomography. The results indicate an inhomogeneous distribution which spreads to a relatively high Mn concentration of 9.0 at. % (at. %). In the paramagnetic phase, it is found that the paramagnetic to ferromagnetic transition takes place sharply with a TC of 334 K when the Mn doping concentration increases to about 4 cat. % Mn, which corresponds to a magnetic percolation threshold for ferromagnetism in (Zn,Mn,Sn)As2. An effective Curie temperature ⟨TC⟩ is considered to bridge the Curie temperatures obtained experimentally to those calculated theoretically in inhomogeneous magnetic semiconductors. The behavior of magnetism in Mn-doped ZnSnAs2 can be explained by three different phases within the present framework.

  10. Effects of Prenatal Cocaine Exposure on Early Sexual Behavior: Gender Difference in Externalizing Behavior as a Mediator

    PubMed Central

    Min, Meeyoung O.; Minnes, Sonia; Lang, Adelaide; Yoon, Susan; Singer, Lynn T.

    2015-01-01

    Background Prenatal cocaine exposure (PCE) is associated with increased risk for externalizing behavior problems; childhood externalizing behavior problems are linked with subsequent early sexual behavior. The present study examined the effects of PCE on early sexual initiation (sexual intercourse prior to age 15) and whether externalizing behavior in preadolescence mediated the relationship. Methods Three hundred fifty-four (180 PCE and 174 non-cocaine exposed; 192 girls, 142 boys), primarily African-American, low socioeconomic status, 15-year old adolescents participated in a prospective longitudinal study. Adolescents’ sexual behavior was assessed at 15 years using the Youth Risk Behavior Surveillance System. Externalizing behavior was assessed at 12 years using the Youth Self-Report. Results Logistic regression models indicated that adolescents with PCE (n=69, 38%) were 2.2 times more likely (95% CI= 1.2 – 4.1, p < .01) to engage in early sexual intercourse than non-exposed peers (n=49, 28%) controlling for covariates. This relationship was fully mediated by self-reported externalizing behavior in girls but not in boys, suggesting childhood externalizing behavior as a gender moderated mediator. Blood lead level during preschool years was also related to a greater likelihood of early sexual intercourse (OR=2.6, 95% CI=1.4 – 4.7, p < .002). Greater parental monitoring decreased the likelihood of early sexual intercourse, while violence exposure increased the risk. Conclusions PCE is related to early sexual intercourse, and externalizing behavior problems mediate PCE effects in female adolescents. Interventions targeting externalizing behavior may reduce early sexual initiation and thereby reduce HIV risk behaviors and early, unplanned pregnancy in girls with PCE. PMID:26088698

  11. Effects of prenatal cocaine exposure on early sexual behavior: Gender difference in externalizing behavior as a mediator.

    PubMed

    Min, Meeyoung O; Minnes, Sonia; Lang, Adelaide; Yoon, Susan; Singer, Lynn T

    2015-08-01

    Prenatal cocaine exposure (PCE) is associated with increased risk for externalizing behavior problems; childhood externalizing behavior problems are linked with subsequent early sexual behavior. The present study examined the effects of PCE on early sexual initiation (sexual intercourse prior to age 15) and whether externalizing behavior in preadolescence mediated the relationship. Three hundred fifty-four (180 PCE and 174 non-cocaine exposed; 192 girls, 142 boys), primarily African-American, low socioeconomic status, 15-year-old adolescents participated in a prospective longitudinal study. Adolescents' sexual behavior was assessed at 15 years using the Youth Risk Behavior Surveillance System. Externalizing behavior was assessed at 12 years using the Youth Self-Report. Logistic regression models indicated that adolescents with PCE (n=69, 38%) were 2.2 times more likely (95% CI=1.2-4.1, p<.01) to engage in early sexual intercourse than non-exposed peers (n=49, 28%) controlling for covariates. This relationship was fully mediated by self-reported externalizing behavior in girls but not in boys, suggesting childhood externalizing behavior as a gender moderated mediator. Blood lead level during preschool years was also related to a greater likelihood of early sexual intercourse (OR=2.6, 95% CI=1.4-4.7, p<.002). Greater parental monitoring decreased the likelihood of early sexual intercourse, while violence exposure increased the risk. PCE is related to early sexual intercourse, and externalizing behavior problems mediate PCE effects in female adolescents. Interventions targeting externalizing behavior may reduce early sexual initiation and thereby reduce HIV risk behaviors and early, unplanned pregnancy in girls with PCE. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Discovery of ferromagnetism with large magnetic anisotropy in ZrMnP and HfMnP

    DOE PAGES

    Lamichhane, Tej N.; Taufour, Valentin; Masters, Morgan W.; ...

    2016-08-29

    Here, ZrMnP and HfMnP single crystals are grown by a self-flux growth technique, and structural as well as temperature dependent magnetic and transport properties are studied. Both compounds have an orthorhombic crystal structure. ZrMnP and HfMnP are ferromagnetic with Curie temperatures around 370 K and 320 K, respectively. The spontaneous magnetizations of ZrMnP and HfMnP are determined to be 1.9 μ B/f.u. and 2.1 μ B/f.u., respectively, at 50 K. The magnetocaloric effect of ZrMnP in terms of entropy change (Δ S) is estimated to be –6.7 kJ m –3 K –1 around 369 K. The easy axis of magnetizationmore » is [100] for both compounds, with a small anisotropy relative to the [010] axis. At 50 K, the anisotropy field along the [001] axis is ~4.6 T for ZrMnP and ~10 T for HfMnP. Such large magnetic anisotropy is remarkable considering the absence of rare-earth elements in these compounds. The first principle calculation correctly predicts the magnetization and hard axis orientation for both compounds, and predicts the experimental HfMnP anisotropy field within 25%. More importantly, our calculations suggest that the large magnetic anisotropy comes primarily from the Mn atoms, suggesting that similarly large anisotropies may be found in other 3d transition metal compounds.« less

  13. Alteration of gene expression by alcohol exposure at early neurulation.

    PubMed

    Zhou, Feng C; Zhao, Qianqian; Liu, Yunlong; Goodlett, Charles R; Liang, Tiebing; McClintick, Jeanette N; Edenberg, Howard J; Li, Lang

    2011-02-21

    We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos. This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube

  14. Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

    PubMed Central

    Das, Rina; Hammamieh, Rasha; Neill, Roger; Ludwig, George V; Eker, Steven; Lincoln, Patrick; Ramamoorthy, Preveen; Dhokalia, Apsara; Mani, Sachin; Mendis, Chanaka; Cummings, Christiano; Kearney, Brian; Royaee, Atabak; Huang, Xiao-Zhe; Paranavitana, Chrysanthi; Smith, Leonard; Peel, Sheila; Kanesa-Thasan, Niranjan; Hoover, David; Lindler, Luther E; Yang, David; Henchal, Erik; Jett, Marti

    2008-01-01

    Background Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs. Methods To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays. Results We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin. Conclusion Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents. PMID:18667072

  15. Improved supercapacitor performance of MnO2-electrospun carbon nanofibers electrodes by mT magnetic field

    NASA Astrophysics Data System (ADS)

    Zeng, Zheng; Liu, Yiyang; Zhang, Wendi; Chevva, Harish; Wei, Jianjun

    2017-08-01

    This work reports on a finding of mT magnetic field induced energy storage enhancement of MnO2-based supercapacitance electrodes (magneto-supercapacitor). Electrodes with MnO2 electrochemically deposited at electrospun carbon nanofibers (ECNFs) film are studied by cyclic voltammetry (CV), galvanostatic charge/discharge, electrochemical impedance spectroscopy (EIS), and life cycle stability tests in the presence/absence of milli-Tesla (mT) magnetic fields derived by Helmholtz coils. In the presence of a 1.34 mT magnetic field, MnO2/ECNFs shows a magneto-enhanced capacitance of 141.7 F g-1 vs. 119.2 F g-1 (∼19% increase) with absence of magnetic field at a voltage sweeping rate of 5 mV s-1. The mechanism of the magneto-supercapacitance is discussed and found that the magnetic susceptibility of the MnO2 significantly improves the electron transfer of a pseudo-redox reaction of Mn(IV)/Mn(III) at the electrode, along with the magnetic field induced impedance effect, which may greatly enhance the interface charge density, facilitate electrolyte transportation, and improve the efficiency of cation intercalation/de-intercalation of the pseudocapacitor under mT-magnetic field exposure, resulting in enhancement of energy storage capacitance and longer charge/discharge time of the MnO2/ECNFs electrode without sacrificing its life cycle stability.

  16. Manganese Exposure from Drinking Water and Children’s Academic Achievement

    PubMed Central

    Khan, Khalid; Wasserman, Gail A.; Liu, Xinhua; Ahmed, Ershad; Parvez, Faruque; Slavkovich, Vesna; Levy, Diane; Mey, Jacob; van Geen, Alexander; Graziano, Joseph H.; Factor-Litvak, Pam

    2012-01-01

    Drinking water manganese (WMn) is a potential threat to children’s health due to its associations with a wide range of outcomes including cognitive, behavioral and neuropsychological effects. Although adverse effects of Mn on cognitive function of the children indicate possible impact on their academic achievement little evidence on this issue is available.. Moreover, little is known regarding potential interactions between exposure to Mn and other metals, especially water arsenic (WAs). In Araihazar, a rural area of Bangladesh, we conducted a cross-sectional study of 840 children to investigate associations between WMn and WAs and academic achievement in mathematics and languages among elementary school-children, aged 8–11 years. Data on As and Mn exposure were collected from the participants at the baseline of an ongoing longitudinal study of school-based educational intervention. Annual scores of the study children in languages (Bangla and English) and mathematics were obtained from the academic achievement records of the elementary schools. WMn above the WHO standard of 400 μg/L was associated with 6.4 percentage score loss (95% CI=0.5, 12.3) in mathematics achievement test scores, adjusted for WAs and other sociodemographic variables. We did not find any significant associations between WMn and academic achievement in either language. Neither WAs nor urinary As was significantly related to any of the three academic achievement scores. Our finding suggests that a large number of children in rural Bangladesh may experience deficits in mathematics due to high concentrations of Mn exposure in drinking water. PMID:22182530

  17. Mn2+ concentration manipulated red emission in BaMg2Si2O7:Eu2+,Mn2+

    NASA Astrophysics Data System (ADS)

    Ye, Song; Zhang, Jiahua; Zhang, Xia; Lu, Shaozhe; Ren, Xinguang; Wang, Xiaojun

    2007-02-01

    The luminescent properties of concentration dependence are reported in BaMg2Si2O7:Eu2+,Mn2+ red phosphor. It is observed that the broad red emission of Mn2+ consists of two bands, located at 620 and 675 nm, respectively, which are attributed to two different Mn2+ centers [Mn2+(I) and Mn2+(II)] substituting for two nonidentical Mg2+ sites [Mg2+(I) and Mg2+(II)] in the host. It is also found that the relative emission intensity of the Mn2+(II) to the Mn2+(I) increases with increasing Mn2+ concentration, leading to a red-shift of the overall emission. A detail analysis on the energy transfer from Eu2+ to the two Mn2+ centers is presented, which indicates that the number ratio of Mn2+(II) to Mn2+(I) increases with increasing Mn2+ concentration. This result is interpreted by the preferential formation of Mn2+(I) substituting for Mg2+(I) site. Based on energy transfer, the emission intensity ratios of Mn2+(I) to Eu2+ and Mn2+(II) to Eu2+, which is Mn2+ concentration dependent, are calculated using related fluorescence lifetimes. The calculated results are in good agreement with that obtained experimentally in the emission spectra.

  18. Collaborative community hazard exposure mapping: Distant Early Warning radar sites in Alaska's North Slope

    NASA Astrophysics Data System (ADS)

    Brady, M.

    2015-12-01

    A method to produce hazard exposure maps that are developed in collaboration with local coastal communities is the focus of this research. Typically efforts to map community exposure to climate threats over large areas have limited consideration of local perspectives about associated risks, constraining their utility for local management. This problem is especially acute in remote locations such as the Arctic where there are unique vulnerabilities to coastal threats that can be fully understood only through inclusion of community stakeholders. Through collaboration with community members, this study identifies important coastal assets and places and surveys local perspectives of exposure to climate threats along Alaska's vast North Slope coastline spanning multiple municipalities. To model physical exposure, the study adapts the U.S. Geological Survey's (USGS) coastal vulnerability index (CVI) to the Arctic context by incorporating the effects of open water distance determined by sea ice extent, and assigning CVI values to coastal assets and places according to direction and proximity. The study found that in addition to concerns about exposed municipal and industrial assets, North Slope communities viewed exposure of traditional activity sites as presenting a particular risk for communities. Highly exposed legacy Cold War Distant Early Warning Line sites are of particular concern with impacts ranging from financial risk to contamination of sensitive coastal marine environments. This research demonstrates a method to collaboratively map community exposure to coastal climate threats to better understand local risks and produce locally usable exposure maps.

  19. Enhanced electrochemical performance of LiMn2O4 by constructing a stable Mn2+-rich interface

    NASA Astrophysics Data System (ADS)

    Lu, Zhongpei; Lu, Xiaojun; Ding, Jingjing; Zhou, Ting; Ge, Tao; Yang, Gang; Yin, Fan; Wu, Mingfang

    2017-12-01

    Spinel LiMn2O4 has drawn continuous attentions due to its low cost, good electrochemical performance, environmental friendliness and natural abundant resources. In view of its severe capacity fading, some types of manganese-based compounds with different Mn oxidation states are selected to protect bare LiMn2O4 by constructing a stable coating layer. In this work, LiMn2O4@LiMnPO4 composite, spherical LiMn2O4 (LMO) as core and Mn2+-rich phase of LiMnPO4 (LMP) as shell, is designed and synthesized. Two composites of LiMn2O4 particles coated with 3 wt% and 10 wt% LiMnPO4 have been compared studied. After 100 cycles at 0.5C rate, the two samples deliver capacity retentions of 96.63% and 93.23% of their initial capacities. Moreover, LMO coated by 3 wt% LiMnPO4 delivers 100.3 mAh g-1 after 200 cycles at 10C rate and 76.3 mAh g-1 after 1000 cycles at 20C rate, much higher than bare LiMn2O4 with 90 mAh g-1 and 45.8 mAh g-1, respectively. This core-shell structure with Mn2+-rich phase as a coating layer effectively enhance the material's cycling performance and rate capacity by reducing the contact of LiMn2O4 with electrolyte.

  20. Cord blood gene expression supports that prenatal exposure to perfluoroalkyl substances causes depressed immune functionality in early childhood.

    PubMed

    Pennings, Jeroen L A; Jennen, Danyel G J; Nygaard, Unni C; Namork, Ellen; Haug, Line S; van Loveren, Henk; Granum, Berit

    2016-01-01

    Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a class of synthetic compounds that have widespread use in consumer and industrial applications. PFAS are considered environmental pollutants that have various toxic properties, including effects on the immune system. Recent human studies indicate that prenatal exposure to PFAS leads to suppressed immune responses in early childhood. In this study, data from the Norwegian BraMat cohort was used to investigate transcriptomics profiles in neonatal cord blood and their association with maternal PFAS exposure, anti-rubella antibody levels at 3 years of age and the number of common cold episodes until 3 years. Genes associated with PFAS exposure showed enrichment for immunological and developmental functions. The analyses identified a toxicogenomics profile of 52 PFAS exposure-associated genes that were in common with genes associated with rubella titers and/or common cold episodes. This gene set contains several immunomodulatory genes (CYTL1, IL27) as well as other immune-associated genes (e.g. EMR4P, SHC4, ADORA2A). In addition, this study identified PPARD as a PFAS toxicogenomics marker. These markers can serve as the basis for further mechanistic or epidemiological studies. This study provides a transcriptomics connection between prenatal PFAS exposure and impaired immune function in early childhood and supports current views on PPAR- and NF-κB-mediated modes of action. The findings add to the available evidence that PFAS exposure is immunotoxic in humans and support regulatory policies to phase out these substances.

  1. Consequences of MnSOD interactions with nitric oxide: nitric oxide dismutation and the generation of peroxynitrite and hydrogen peroxide.

    PubMed

    Filipović, Milos R; Stanić, Dragana; Raicević, Smiljana; Spasić, Mihajlo; Niketić, Vesna

    2007-01-01

    The present study demonstrates that manganese superoxide dismutase (MnSOD) (Escherichia coli), binds nitric oxide (*NO) and stimulates its decay under both anaerobic and aerobic conditions. The results indicate that previously observed MnSOD-catalyzed *NO disproportionation (dismutation) into nitrosonium (NO+) and nitroxyl (NO-) species under anaerobic conditions is also operative in the presence of molecular oxygen. Upon sustained aerobic exposure to *NO, MnSOD-derived NO- species initiate the formation of peroxynitrite (ONOO-) leading to enzyme tyrosine nitration, oxidation and (partial) inactivation. The results suggest that both ONOO- decomposition and ONOO(-)-dependent tyrosine residue nitration and oxidation are enhanced by metal centre-mediated catalysis. We show that the generation of ONOO- is accompanied by the formation of substantial amounts of H2O2. MnSOD is a critical mitochondrial antioxidant enzyme, which has been found to undergo tyrosine nitration and inactivation in various pathologies associated with the overproduction of *NO. The results of the present study can account for the molecular specificity of MnSOD nitration in vivo. The interaction of *NO with MnSOD may represent a novel mechanism by which MnSOD protects the cell from deleterious effects associated with overproduction of *NO.

  2. Formation of self-organized Mn3O4 nanoinclusions in LaMnO3 films

    NASA Astrophysics Data System (ADS)

    Pomar, Alberto; Konstantinović, Zorica; Bagués, Nuria; Roqueta, Jaume; López-Mir, Laura; Balcells, Lluis; Frontera, Carlos; Mestres, Narcis; Gutiérrez-Llorente, Araceli; Šćepanović, Maja; Lazarević, Nenad; Popović, Zoran; Sandiumenge, Felip; Martínez, Benjamín; Santiso, José

    2016-09-01

    We present a single-step route to generate ordered nanocomposite thin films of secondary phase inclusions (Mn3O4) in a pristine perovskite matrix (LaMnO3) by taking advantage of the complex phase diagram of manganese oxides. We observed that in samples grown under vacuum growth conditions from a single LaMnO3 stoichiometric target by Pulsed Laser Deposition, the most favourable mechanism to accommodate Mn2+ cations is the spontaneous segregation of self-assembled wedge-like Mn3O4 ferrimagnetic inclusions inside a LaMnO3 matrix that still preserves its orthorhombic structure and its antiferromagnetic bulk-like behaviour. A detailed analysis on the formation of the self-assembled nanocomposite films evidences that Mn3O4 inclusions exhibit an epitaxial relationship with the surrounding matrix that it may be explained in terms of a distorted cubic spinel with slight ( 9º) c-axis tilting. Furthermore, a Ruddlesden-Popper La2MnO4 phase, helping to the stoichiometry balance, has been identified close to the interface with the substrate. We show that ferrimagnetic Mn3O4 columns influence the magnetic and transport properties of the nanocomposite by increasing its coercive field and by creating local areas with enhanced conductivity in the vicinity of the inclusions.

  3. Critical Evaluations and Thermodynamic Optimizations of the MnO-Mn2O3-SiO2 and FeO-Fe2O3-MnO-Mn2O3-SiO2 Systems

    NASA Astrophysics Data System (ADS)

    Kang, Youn-Bae; Jung, In-Ho

    2017-06-01

    A critical evaluation and thermodynamic modeling for thermodynamic properties of all oxide phases and phase diagrams in the Fe-Mn-Si-O system (MnO-Mn2O3-SiO2 and FeO-Fe2O3-MnO-Mn2O3-SiO2 systems) are presented. Optimized Gibbs energy parameters for the thermodynamic models of the oxide phases were obtained which reproduce all available and reliable experimental data within error limits from 298 K (25°C) to above the liquidus temperatures at all compositions covering from known oxide phases, and oxygen partial pressure from metal saturation to 0.21 bar. The optimized thermodynamic properties and phase diagrams are believed to be the best estimates presently available. Slag (molten oxide) was modeled using the modified quasichemical model in the pair approximation. Olivine (Fe2SiO4-Mn2SiO4) was modeled using two-sublattice model in the framework of the compound energy formalism (CEF), while rhodonite (MnSiO3-FeSiO3) and braunite (Mn7SiO_{12} with excess Mn2O3) were modeled as simple Henrian solutions. It is shown that the already developed models and databases of two spinel phases (cubic- and tetragonal-(Fe, Mn)3O4) using CEF [Kang and Jung, J. Phys. Chem. Solids (2016), vol. 98, pp. 237-246] can successfully be integrated into a larger thermodynamic database to be used in practically important higher order system such as silicate. The database of the model parameters can be used along with a software for Gibbs energy minimization in order to calculate any type of phase diagram section and thermodynamic properties.

  4. Inhibition of Calpains Protects Mn-Induced Neurotransmitter release disorders in Synaptosomes from Mice: Involvement of SNARE Complex and Synaptic Vesicle Fusion.

    PubMed

    Wang, Can; Xu, Bin; Ma, Zhuo; Liu, Chang; Deng, Yu; Liu, Wei; Xu, Zhao-Fa

    2017-06-16

    Overexposure to manganese (Mn) could disrupt neurotransmitter release via influencing the formation of SNARE complex, but the underlying mechanisms are still unclear. A previous study demonstrated that SNAP-25 is one of substrate of calpains. The current study investigated whether calpains were involved in Mn-induced disorder of SNARE complex. After mice were treated with Mn for 24 days, Mn deposition increased significantly in basal nuclei in Mn-treated and calpeptin pre-treated groups. Behaviorally, less time spent in the center of the area and decreased average velocity significantly in an open field test after 24 days of Mn exposure. With the increase in MnCl 2 dosage, intracellular Ca 2+ increased significantly, but pretreatment with calpeptin caused a dose-dependent decrease in calpains activity. There were fragments of N-terminal of SNAP-25 protein appearance in Mn-treated groups, but it is decreased with pretreatment of calpeptin. FM1-43-labeled synaptic vesicles also provided evidence that the treatment with Mn resulted in increasing first and then decreasing, which was consistent with Glu release and the 80 kDa protein levels of SNARE complexes. In summary, Mn induced the disorder of neurotransmitter release through influencing the formation of SNARE complex via cleaving SNAP-25 by overactivation of calpains in vivo.

  5. Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure.

    PubMed

    Barbier, Estelle; Pierrefiche, Olivier; Vaudry, David; Vaudry, Hubert; Daoust, Martine; Naassila, Mickaël

    2008-12-01

    Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring.

  6. Developmental manganese exposure in combination with developmental stress and iron deficiency: Effects on behavior and monoamines.

    PubMed

    Amos-Kroohs, Robyn M; Davenport, Laurie L; Gutierrez, Arnold; Hufgard, Jillian R; Vorhees, Charles V; Williams, Michael T

    2016-01-01

    Manganese (Mn) is an essential element but neurotoxic at higher exposures, however, Mn exposure seldom occurs in isolation. It often co-occurs in populations with inadequate dietary iron (Fe) and limited resources that result in stress. Subclinical FeD affects up to 15% of U.S. children and exacerbates Mn toxicity by increasing Mn bioavailability. Therefore, we investigated Mn overexposure (MnOE) in rats in combination with Fe deficiency (FeD) and developmental stress, for which we used barren cage rearing. For barren cage rearing (BAR), rats were housed in cages with a wire grid floor or standard bedding material (STD) from embryonic day (E)7 through postnatal day (P)28. For FeD, dams were fed a 90% Fe-deficient NIH-07 diet from E15 through P28. Within each litter, different offspring were treated with 100mg/kg Mn (MnOE) or vehicle (VEH) by gavage every other day from P4-28. Behavior was assessed at two ages and consisted of: open-field, anxiety tests, acoustic startle response (ASR) with prepulse inhibition (PPI), sociability, sucrose preference, tapered beam crossing, and the Porsolt's forced swim test. MnOE had main effects of decreasing activity, ASR, social preference, and social novelty. BAR and FeD transiently modified MnOE effects. BAR groups weighed less and showed decreased anxiety in the elevated zero maze, had increased ASR and decreased PPI, and exhibited reduced sucrose preference compared with the STD groups. FeD animals also weighed less and had increased slips on the tapered beam. Most of the monoamine effects were dopaminergic and occurred in the MnOE groups. The results showed that Mn is a pervasive developmental neurotoxin, the effects of which are modulated by FeD and/or BAR cage rearing. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Cat exposure in early life decreases asthma risk from the 17q21 high-risk variant.

    PubMed

    Stokholm, Jakob; Chawes, Bo L; Vissing, Nadja; Bønnelykke, Klaus; Bisgaard, Hans

    2018-05-01

    Early-life exposure to cats and dogs has shown diverging associations with childhood asthma risk, and gene-environment interaction is one possible explanation. We investigated interactions between cat and dog exposure and single nucleotide polymorphism rs7216389 variants in the chromosome 17q21 locus, the strongest known genetic risk factor for childhood asthma. Genotyping was performed in 377 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 . The primary end point was the development of asthma until age 12 years. The secondary end point was the number of episodes with pneumonia and bronchiolitis from 0 to 3 years of age. Exposures included cat and dog ownership from birth and cat and dog allergen levels in bedding at age 1 year. Replication was performed in the unselected COPSAC 2010 cohort with follow-up until 5 years of age. Cat and/or dog exposure from birth was associated with a lower prevalence of asthma among children with the rs7216389 high-risk TT genotype (adjusted hazard ratio, 0.16; 95% CI, 0.04-0.71; P = .015), with no effect in those with the CC/CT genotype (adjusted P = .283), demonstrating interaction between cat and dog exposure and the rs7216389 genotype (adjusted P = .044). Cat allergen levels were inversely associated with asthma development in children with the TT genotype (adjusted hazard ratio, 0.83; 95% CI, 0.71-0.97; P = .022), supporting the cat-rs7216389 genotype interaction (adjusted P = .008). Dog allergen exposure did not show such interaction. Furthermore, the TT genotype was associated with higher risk of pneumonia and bronchiolitis, and this increased risk was likewise decreased in children exposed to cat. Replication showed similar effects on asthma risk. The observed gene-environment interaction suggests a role of early-life exposure, especially to cat, for attenuating the risk of childhood asthma, pneumonia, and bronchiolitis in genetically susceptible subjects. Copyright © 2017

  8. Early Life Fructose Exposure and Its Implications for Long-Term Cardiometabolic Health in Offspring.

    PubMed

    Zheng, Jia; Feng, Qianyun; Zhang, Qian; Wang, Tong; Xiao, Xinhua

    2016-11-01

    It has become increasingly clear that maternal nutrition can strongly influence the susceptibility of adult offspring to cardiometabolic disease. For decades, it has been thought that excessive intake of fructose, such as sugar-sweetened beverages and foods, has been linked to increased risk of obesity, type 2 diabetes, and cardiovascular disease in various populations. These deleterious effects of excess fructose consumption in adults are well researched, but limited data are available on the long-term effects of high fructose exposure during gestation, lactation, and infancy. This review aims to examine the evidence linking early life fructose exposure during critical periods of development and its implications for long-term cardiometabolic health in offspring.

  9. Chlorpyrifos Exposure and Urban Residential Environment Characteristics as Determinants of Early Childhood Neurodevelopment

    PubMed Central

    Quinn, James W.; Rauh, Virginia A.; Perera, Frederica P.; Andrews, Howard F.; Garfinkel, Robin; Hoepner, Lori; Whyatt, Robin; Rundle, Andrew

    2011-01-01

    Objectives. We evaluated whether neighborhood characteristics correlated with early neurodevelopment and whether these characteristics confounded the previously reported association between exposure to chlorpyrifos (an organophosphate insecticide) and neurodevelopment. Methods. We obtained prenatal addresses, chlorpyrifos exposure data, and 36-month Psychomotor Development Index (PDI) and Mental Development Index (MDI) scores for a birth cohort in New York City (born 1998–2002). We used data from the 2000 US Census to estimate measures of physical infrastructure, socioeconomic status, crowding, demographic composition, and linguistic isolation for 1-kilometer network areas around each child's prenatal address. Generalized estimating equations were adjusted for demographics, maternal education and IQ, prenatal exposure to tobacco smoke, caretaking environment quality, and building dilapidation. Results. Of 266 children included as participants, 47% were male, 59% were Dominican, and 41% were African American. For each standard deviation higher in neighborhood percent poverty, the PDI score was 2.6 points lower (95% confidence interval [CI] = −3.7, −1.5), and the MDI score was 1.7 points lower (95% CI = −2.6, −0.8). Neighborhood-level confounding of the chlorpyrifos-neurodevelopment association was not apparent. Conclusions. Neighborhood context and chlorpyrifos exposure were independently associated with neurodevelopment, thus providing distinct opportunities for health promotion. PMID:20299657

  10. Surface Reactivity of Li2MnO3: First-Principles and Experimental Study.

    PubMed

    Quesne-Turin, Ambroise; Flahaut, Delphine; Croguennec, Laurence; Vallverdu, Germain; Allouche, Joachim; Charles-Blin, Youn; Chotard, Jean-Noël; Ménétrier, Michel; Baraille, Isabelle

    2017-12-20

    This article deals with the surface reactivity of (001)-oriented Li 2 MnO 3 crystals investigated from a multitechnique approach combining material synthesis, X-ray photoemission spectroscopy (XPS), scanning electron microscopy, Auger electron spectroscopy, and first-principles calculations. Li 2 MnO 3 is considered as a model compound suitable to go further in the understanding of the role of tetravalent manganese atoms in the surface reactivity of layered lithium oxides. The knowledge of the surface properties of such materials is essential to understand the mechanisms involved in parasitic phenomena responsible for early aging or poor storage performances of lithium-ion batteries. The surface reactivity was probed through the adsorption of SO 2 gas molecules on large Li 2 MnO 3 crystals to be able to focus the XPS beam on the top of the (001) surface. A chemical mapping and XPS characterization of the material before and after SO 2 adsorption show in particular that the adsorption is homogeneous at the micro- and nanoscale and involves Mn reduction, whereas first-principles calculations on a slab model of the surface allow us to conclude that the most energetically favorable species formed is a sulfate with charge transfer implying reduction of Mn.

  11. Enzymatic microbial Mn(II) oxidation and Mn biooxide production in the Guaymas Basin deep-sea hydrothermal plume

    NASA Astrophysics Data System (ADS)

    Dick, Gregory J.; Clement, Brian G.; Webb, Samuel M.; Fodrie, F. Joel; Bargar, John R.; Tebo, Bradley M.

    2009-11-01

    Microorganisms play important roles in mediating biogeochemical reactions in deep-sea hydrothermal plumes, but little is known regarding the mechanisms that underpin these transformations. At Guaymas Basin (GB) in the Gulf of California, hydrothermal vents inject fluids laden with dissolved Mn(II) (dMn) into the deep waters of the basin where it is oxidized and precipitated as particulate Mn(III/IV) oxides, forming turbid hydrothermal "clouds". Previous studies have predicted extremely short residence times for dMn at GB and suggested they are the result of microbially-mediated Mn(II) oxidation and precipitation. Here we present biogeochemical results that support a central role for microorganisms in driving Mn(II) oxidation in the GB hydrothermal plume, with enzymes being the primary catalytic agent. dMn removal rates at GB are remarkably fast for a deep-sea hydrothermal plume (up to 2 nM/h). These rapid rates were only observed within the plume, not in background deep-sea water above the GB plume or at GB plume depths (˜1750-2000 m) in the neighboring Carmen Basin, where there is no known venting. dMn removal is dramatically inhibited under anoxic conditions and by the presence of the biological poison, sodium azide. A conspicuous temperature optimum of dMn removal rates (˜40 °C) and a saturation-like (i.e. Michaelis-Menten) response to O 2 concentration were observed, indicating an enzymatic mechanism. dMn removal was resistant to heat treatment used to select for spore-forming organisms, but very sensitive to low concentrations of added Cu, a cofactor required by the putative Mn(II)-oxidizing enzyme. Extended X-ray absorption fine structure spectroscopy (EXAFS) and synchrotron radiation-based X-ray diffraction (SR-XRD) revealed the Mn oxides to have a hexagonal birnessite or δ-MnO 2-like mineral structure, indicating that these freshly formed deep-sea Mn oxides are strikingly similar to primary biogenic Mn oxides produced by laboratory cultures of bacteria

  12. Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Leu, Yu-Wei; Chu, Pei-Yi; Chen, Chien-Min

    Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodentmore » model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms.« less

  13. Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight.

    PubMed

    Kippler, Maria; Engström, Karin; Mlakar, Simona Jurkovic; Bottai, Matteo; Ahmed, Sultan; Hossain, Mohammad Bakhtiar; Raqib, Rubhana; Vahter, Marie; Broberg, Karin

    2013-05-01

    Dietary cadmium exposure was recently found to alter DNA methylation in adults, but data on effects early in life are lacking. Our objective was to evaluate associations between prenatal cadmium exposure, DNA methylation and birth weight. In total 127 mother-child pairs from rural Bangladesh were studied. For comparison, we included 56 children at 4.5 y. Cadmium concentrations in mothers' blood (gestational week 14) and children's urine were measured by ICPMS. Global DNA methylation was analyzed by Infinium HumanMethylation450K BeadChip in cord blood and children's blood. Maternal cadmium exposure was associated with cord blood DNA methylation (p-value < 10 (-16) ). The association was markedly sex-specific. In boys, 96% of the top 500 CpG sites showed positive correlations (rS-values > 0.50), whereas most associations in girls were inverse; only 29% were positive (rS > 0.45). In girls we found overrepresentation of methylation changes in genes associated with organ development, morphology and mineralization of bone, whereas changes in boys were found in cell death-related genes. Several individual CpG sites that were positively associated with cadmium were inversely correlated with birth weight, although none statistically significant after correction for multiple comparisons. The associations were, however, fairly robust in multivariable-adjusted linear regression models. We identified CpG sites that were significantly associated with cadmium exposure in both newborns and 4.5-y-old children. In conclusion, cadmium exposure in early life appears to alter DNA methylation differently in girls and boys. This is consistent with previous findings of sex-specific cadmium toxicity. Cadmium-related changes in methylation were also related to lower birth weight.

  14. Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight

    PubMed Central

    Kippler, Maria; Engström, Karin; Mlakar, Simona Jurkovic; Bottai, Matteo; Ahmed, Sultan; Hossain, Mohammad Bakhtiar; Raqib, Rubhana; Vahter, Marie; Broberg, Karin

    2013-01-01

    Dietary cadmium exposure was recently found to alter DNA methylation in adults, but data on effects early in life are lacking. Our objective was to evaluate associations between prenatal cadmium exposure, DNA methylation and birth weight. In total 127 mother-child pairs from rural Bangladesh were studied. For comparison, we included 56 children at 4.5 y. Cadmium concentrations in mothers’ blood (gestational week 14) and children’s urine were measured by ICPMS. Global DNA methylation was analyzed by Infinium HumanMethylation450K BeadChip in cord blood and children’s blood. Maternal cadmium exposure was associated with cord blood DNA methylation (p-value < 10–16). The association was markedly sex-specific. In boys, 96% of the top 500 CpG sites showed positive correlations (rS-values > 0.50), whereas most associations in girls were inverse; only 29% were positive (rS > 0.45). In girls we found overrepresentation of methylation changes in genes associated with organ development, morphology and mineralization of bone, whereas changes in boys were found in cell death-related genes. Several individual CpG sites that were positively associated with cadmium were inversely correlated with birth weight, although none statistically significant after correction for multiple comparisons. The associations were, however, fairly robust in multivariable-adjusted linear regression models. We identified CpG sites that were significantly associated with cadmium exposure in both newborns and 4.5-y-old children. In conclusion, cadmium exposure in early life appears to alter DNA methylation differently in girls and boys. This is consistent with previous findings of sex-specific cadmium toxicity. Cadmium-related changes in methylation were also related to lower birth weight. PMID:23644563

  15. Mutation in HFE gene decreases manganese accumulation and oxidative stress in the brain after olfactory manganese exposure.

    PubMed

    Ye, Qi; Kim, Jonghan

    2016-06-01

    Increased accumulation of manganese (Mn) in the brain is significantly associated with neurobehavioral deficits and impaired brain function. Airborne Mn has a high systemic bioavailability and can be directly taken up into the brain, making it highly neurotoxic. While Mn transport is in part mediated by several iron transporters, the expression of these transporters is altered by the iron regulatory gene, HFE. Mutations in the HFE gene are the major cause of the iron overload disorder, hereditary hemochromatosis, one of the prevalent genetic diseases in humans. However, whether or not HFE mutation modifies Mn-induced neurotoxicity has not been evaluated. Therefore, our goal was to define the role of HFE mutation in Mn deposition in the brain and the resultant neurotoxic effects after olfactory Mn exposure. Mice carrying the H67D HFE mutation, which is homologous to the H63D mutation in humans, and their control, wild-type mice, were intranasally instilled with MnCl2 with different doses (0, 0.2, 1.0 and 5.0 mg kg(-1)) daily for 3 days. Mn levels in the blood, liver and brain were determined using inductively-coupled plasma mass spectrometry (ICP-MS). H67D mutant mice showed significantly lower Mn levels in the blood, liver, and most brain regions, especially in the striatum, while mice fed an iron-overload diet did not. Moreover, mRNA expression of ferroportin, an essential exporter of iron and Mn, was up-regulated in the striatum. In addition, the levels of isoprostane, a marker of lipid peroxidation, were increased in the striatum after Mn exposure in wild-type mice, but were unchanged in H67D mice. Together, our results suggest that the H67D mutation provides decreased susceptibility to Mn accumulation in the brain and neurotoxicity induced by inhaled Mn.

  16. Early life urban exposure as a risk factor for developing obesity and impaired fasting glucose in later adulthood: results from two cohorts in Thailand.

    PubMed

    Angkurawaranon, Chaisiri; Wisetborisut, Anawat; Rerkasem, Kittipan; Seubsman, Sam-Ang; Sleigh, Adrian; Doyle, Pat; Nitsch, Dorothea

    2015-09-16

    Obesity and obesity related conditions, driven by processes such as urbanization and globalization, are contributing to pronounced cardiovascular morbidity and mortality in developing countries. There is limited evidence on the influence of living in an urban environment in early life on obesity and obesity related conditions later in life in developing countries such as Thailand. We used data from two cohort studies conducted in Thailand, the Thai Cohort Study (TCS) and the Chiang Mai University (CMU) Health Worker Study, to investigate the association between early life urban (vs rural) exposure and the later development of obesity. We additionally explored the association between early life urban exposure and impaired fasting glucose in adulthood using data from the CMU Health Worker Study. Among 48,490 adults from the TCS, 9.1 % developed obesity within 4 years of follow-up. Among 1,804 initially non-obese adults from CMU Health worker study, 13.6 % developed obesity within 5 years of follow-up. Early life urban exposure was associated with increased risk of developing obesity in adulthood in both cohorts. Adjusting for age and sex, those who spent their early lives in urban areas were 1.21 times more likely to develop obesity in the TCS (OR 1.21, 95 % CI 1.12 to 1.31) and 1.65 times more likely in the CMU Health Worker study (OR 1.65, 95 % CI 1.23 to 2.20). These associations remained significant despite adjustment for later life urban exposure and current household income. No evidence for an association was found for impaired fasting glucose. Early life urban exposure was associated with increased risk of developing obesity in adulthood. These findings support public health intervention programs to prevent obesity starting from early ages.

  17. Early valproic acid exposure alters functional organization in the primary visual cortex

    PubMed Central

    Pohl-Guimaraes, Fernanda; Krahe, Thomas E.; Medina, Alexandre E.

    2018-01-01

    Epilepsy is one of the most common neurologic disorders and affects 0.5 to 1% of pregnant women. The use of antiepileptic drugs, which is usually continued throughout pregnancy, can cause in offspring mild to severe sensory deficits. Neuronal selectivity to stimulus orientation is a basic functional property of the visual cortex that is crucial for perception of shapes and borders. Here we investigate the effects of early exposure to valproic acid (Val) and levetiracetam (Lev), commonly used antiepileptic drugs, on the development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets pups were exposed to Val (200 mg/kg), Lev (100 mg/kg) or saline every other day between postnatal day (P) 10 and P30, a period roughly equivalent to the third trimester of human gestation. Optical imaging of intrinsic signals or single-unit recordings were examined at P42–P84, when orientation selectivity in the ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in Val-but not Lev- or saline-treated animals. Moreover, single-unit recordings revealed that early Val treatment also reduced orientation selectivity at the cellular level. These findings indicate that Val exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in fetal anticonvulsant syndrome. PMID:21215743

  18. Early valproic acid exposure alters functional organization in the primary visual cortex.

    PubMed

    Pohl-Guimaraes, Fernanda; Krahe, Thomas E; Medina, Alexandre E

    2011-03-01

    Epilepsy is one of the most common neurologic disorders and affects 0.5 to 1% of pregnant women. The use of antiepileptic drugs, which is usually continued throughout pregnancy, can cause in offspring mild to severe sensory deficits. Neuronal selectivity to stimulus orientation is a basic functional property of the visual cortex that is crucial for perception of shapes and borders. Here we investigate the effects of early exposure to valproic acid (Val) and levetiracetam (Lev), commonly used antiepileptic drugs, on the development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets pups were exposed to Val (200mg/kg), Lev (100mg/kg) or saline every other day between postnatal day (P) 10 and P30, a period roughly equivalent to the third trimester of human gestation. Optical imaging of intrinsic signals or single-unit recordings were examined at P42-P84, when orientation selectivity in the ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in Val- but not Lev- or saline-treated animals. Moreover, single-unit recordings revealed that early Val treatment also reduced orientation selectivity at the cellular level. These findings indicate that Val exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in fetal anticonvulsant syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Yue; Xie, Changchun; Murphy, Susan K.

    Here, lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study frommore » birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. Our

  20. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    DOE PAGES

    Li, Yue; Xie, Changchun; Murphy, Susan K.; ...

    2015-06-26

    Here, lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study frommore » birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. Our

  1. Acute myeloid leukaemia at an early age: Reviewing the interaction between pesticide exposure and KMT2A-rearrangement

    PubMed Central

    Pombo-de-Oliveira, Maria S; Andrade, Francianne Gomes; Brisson, Gisele Dallapicola; dos Santos Bueno, Filipe Vicente; Cezar, Ingrid Sardou; Noronha, Elda Pereira

    2017-01-01

    Acute myeloid leukaemia (AML) in early childhood is characterised by a high frequency of recurrent genomic aberrations associated with distinct myeloid subtypes, clinical outcomes and pathogenesis. Genomic instability is the first step of pathogenic mechanism in early childhood AML. A sum of adverse events is necessary to the development of infant AML (i-AML), which includes latency of biochemical-molecular and cellular effects. Inherited genetic susceptibility associated with exposures to biotransformation substances can modulate the risk of DNA damage and it is a very important piece in the pathogenic puzzle. In this review, we have aimed to explore the chain of events in the time-points of the natural history of i-AML, which includes maternal exposures during pregnancy, the speculations about the formation of somatic mutations during foetal life and the secondary genomic aberrations associated with i-AML. The modulation of risk conferred by xenobiotic metabolism´s genes variants is the bottom line of the pathogenic process. Since we have conducted observational and molecular investigations in early childhood leukaemia, the data focused here is based on Brazilian findings with summarised results of our experience with epidemiological and molecular studies in early-age leukaemia. PMID:29225689

  2. Antiferromagnetism in semiconducting SrMn2Sb2 and BaMn2Sb2 single crystals

    NASA Astrophysics Data System (ADS)

    Sangeetha, N. S.; Smetana, V.; Mudring, A.-V.; Johnston, D. C.

    2018-01-01

    Crystals of SrMn2Sb2 and BaMn2Sb2 were grown using Sn flux and characterized by powder and single-crystal x-ray diffraction, respectively, and by single-crystal electrical resistivity ρ , heat capacity Cp, and magnetic susceptibility χ measurements versus temperature T , and magnetization versus field M (H ) isotherm measurements. SrMn2Sb2 adopts the trigonal CaAl2Si2 -type structure, whereas BaMn2Sb2 crystallizes in the tetragonal ThCr2Si2 -type structure. The ρ (T ) data indicate semiconducting behaviors for both compounds with activation energies of ≳0.35 eV for SrMn2Sb2 and 0.16 eV for BaMn2Sb2 . The χ (T ) and Cp(T ) data reveal antiferromagnetic (AFM) ordering at TN = 110 K for SrMn2Sb2 and 450 K for BaMn2Sb2 . The anisotropic χ (T ≤TN) data also show that the ordered moments in SrMn2Sb2 are aligned in the hexagonal a b plane, whereas the ordered moments in BaMn2Sb2 are aligned collinearly along the tetragonal c axis. The a b -plane M (H ) data for SrMn2Sb2 exhibit a continuous metamagnetic transition at low fields 0 Mn2Sb2 exhibits no metamagnetic transitions up to 5.5 T. The χ (T ) and C p(T ) data for both SrMn2Sb2 and BaMn2Sb2 indicate strong dynamic short-range AFM correlations above their respective TN up to at least 900 K within a local-moment picture, corresponding to quasi-two-dimensional magnetic behavior. The present results and a survey of the literature for Mn pnictides with the CaAl2Si2 and ThCr2Si2 crystal structures show that the TN values for the CaAl2Si2 -type compounds are much smaller than those for the ThCr2Si2 -type materials.

  3. Sulfur Mediated Alleviation of Mn Toxicity in Polish Wheat Relates to Regulating Mn Allocation and Improving Antioxidant System

    PubMed Central

    Sheng, Huajin; Zeng, Jian; Liu, Yang; Wang, Xiaolu; Wang, Yi; Kang, Houyang; Fan, Xing; Sha, Lina; Zhang, Haiqin; Zhou, Yonghong

    2016-01-01

    Sulfur (S) is an essential macronutrient that has been proved to play an important role in regulating plant responses to various biotic and abiotic stresses. The present study was designed to investigate the effect of S status on polish wheat plant response to Mn toxicity. Results showed that Mn stress inhibited plant growth, disturbed photosynthesis and induced oxidative stress. In response to Mn stress, polish wheat plant activated several detoxification mechanisms to counteract Mn toxicity, including enhanced antioxidant defense system, increased Mn distribution in the cell wall and up-regulated genes involved in S assimilation. Moderate S application was found to alleviate Mn toxicity mainly by sequestering excess Mn into vacuoles, inhibiting Mn translocation from roots to shoots, stimulating activities of antioxidant enzymes and enhancing GSH production via up-regulating genes involved in S metabolism. However, application of high level S to Mn-stressed plants did not significantly alleviated Mn toxicity likely due to osmotic stress. In conclusion, moderate S application is beneficial to polish wheat plant against Mn toxicity, S exerts its effects via stimulating the antioxidant defense system and regulating the translocation and subcellular distribution of Mn, in which processes GSH plays an indispensable role. PMID:27695467

  4. Brief Report: Do Delinquency and Community Violence Exposure Explain Internalizing Problems in Early Adolescent Gang Members?

    ERIC Educational Resources Information Center

    Madan, Anjana; Mrug, Sylvie; Windle, Michael

    2011-01-01

    Adolescent gang members are at higher risk for internalizing problems as well as exposure to community violence and delinquency. This study examined whether gang membership in early adolescence is associated with internalizing problems (depression, anxiety, and suicidal behavior) and whether these associations are mediated by delinquency and…

  5. Air exposure assessment and biological monitoring of manganese and other major welding fume components in welders.

    PubMed

    Ellingsen, Dag G; Dubeikovskaya, Larisa; Dahl, Kari; Chashchin, Maxim; Chashchin, Valery; Zibarev, Evgeny; Thomassen, Yngvar

    2006-10-01

    In a cross-sectional study, 96 welders were compared with 96 control subjects. Also 27 former welders, all diagnosed as having manganism, were examined. Exposure to welding fumes was determined in the 96 welders, while the concentration of elements in whole blood and urine was determined in all subjects. The geometric mean (GM) concentrations of manganese (Mn) and iron in the workroom air were 97 microg m(-3) (range 3-4620 microg m(-3); n=188) and 894 microg m(-3) (range 106-20 300 microg m(-3); n=188), respectively. Thus the Mn concentration in the workroom air was on average 10.6% (GM) of that of the Fe concentration. No substantial difference was observed in the air Mn concentrations when welding mild steel as compared to welding stainless steel. The arithmetic mean (AM) concentration of Mn in whole blood (B-Mn) was about 25% higher in the welders compared to the controls (8.6 vs. 6.9 microg l(-1); p < 0.001), while the difference in the urinary Mn concentrations did not attain statistical significance. A Pearson's correlation coefficient of 0.31 (p < 0.01) was calculated between B-Mn and Mn in the workroom air that was collected the day before blood sampling. Although the exposure to welding fumes in the patients had ceased on average 5.8 years prior to the study (range 4 years-7 years), their AM B-Mn concentration was still higher than in referents of similar age (8.7 microg l(-1) vs. 7.0 microg l(-1)). However, their urinary concentrations of cobolt, iron and Mn were all statistically significantly lower.

  6. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

    PubMed Central

    2011-01-01

    Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3) by inhalation over 6 months. Results DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Conclusions Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of

  7. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease.

    PubMed

    Levesque, Shannon; Surace, Michael J; McDonald, Jacob; Block, Michelle L

    2011-08-24

    Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months. DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m³ significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m³ and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m³) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m³ exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain.

  8. Early Exposure to Movie Smoking Predicts Established Smoking by Older Teens and Young Adults

    PubMed Central

    Dalton, Madeline A.; Beach, Michael L.; Adachi-Mejia, Anna M.; Longacre, Meghan R.; Matzkin, Aurora L.; Sargent, James D.; Heatherton, Todd F.; Titus-Ernstoff, Linda

    2009-01-01

    OBJECTIVE Movie smoking exposure is a strong predictor of smoking initiation by adolescents; however, we do not know whether it is a long-term predictor of established smoking. We conducted a prospective study to determine whether movie smoking exposure during early adolescence predicts established smoking in older teens and young adults. DESIGN We assessed movie smoking exposure and smoking status through a written school-based survey in 1999, when participants were 10 to 14 years of age. We enrolled 73% (n = 2603) of those who had never tried smoking in a follow-up study. In 2006–2007, we conducted telephone interviews with 69% (n = 1791) of the cohort to ascertain current smoking status. The primary outcome was established smoking, defined as having smoked >100 cigarettes. Mean age at follow-up was 18.7 years. RESULTS Thirteen percent (n = 235) progressed from never smoking to established smoking during the follow-up period. Eighty-nine percent (n = 209) of established smokers smoked during the 30 days before the survey. Even after controlling for a wide range of baseline characteristics, the relative risk for established smoking increased by one third with each successive quartile of movie smoking exposure. Those in the highest quartile for baseline movie smoking exposure were twice as likely to be established smokers at follow-up compared with those in the lowest quartile. CONCLUSIONS Movie smoking exposure significantly predicted progression to established smoking in long-term follow-up. We estimate that 34.9% of established smoking in this cohort can be attributed to movie smoking exposure. PMID:19336346

  9. Unknown risk: co-exposure to lead and other heavy metals among children living in small-scale mining communities in Zamfara State, Nigeria.

    PubMed

    Bartrem, Casey; Tirima, Simba; von Lindern, Ian; von Braun, Margrit; Worrell, Mary Claire; Mohammad Anka, Shehu; Abdullahi, Aishat; Moller, Gregory

    2014-08-01

    The lead poisoning crisis in Zamfara State, Northern Nigeria has been called the worst such case in modern history and it presents unique challenges for risk assessment and management of co-exposure to multiple heavy metals. More than 400 children have died in Zamfara as a result of ongoing lead intoxication since early in 2010. A review of the common toxic endpoints of the major heavy metals advances analysis of co-exposures and their common pathologies. Environmental contamination in Bagega village, examined by X-ray fluorescence of soils, includes lead, mercury, cadmium, arsenic and manganese. Co-exposure risk is explored by scoring common toxic endpoints and hazard indices to calculate a common pathology hazard risk ranking of Pb > As > Hg > Cd > Mn. Zamfara presents an extreme picture of both lead and multiple heavy metal mortality and morbidity, but similar situations have become increasingly prevalent worldwide.

  10. Effect of chronic copper and pentachlorophenol exposure to early life stages of Xenopus laevis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fort, D.J.; Stover, E.L.

    1995-12-31

    An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorophenol, from 0 d to 4 d (standard Frog Embryo Teratagenesis Assay Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased inmore » each successive time period. Continuous exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5/{micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.« less

  11. Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from Event-Related Potentials

    PubMed Central

    Grégoire, Laurent; Caparos, Serge; Leblanc, Carole-Anne; Brisson, Benoit; Blanchette, Isabelle

    2018-01-01

    This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD) and no abuse participants. We focused particularly on an early wave (C1/P1), the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms) of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD) suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology. PMID:29379428

  12. Post-GOE redox insights from Mo isotopes, Ce anomalies, and Mn from the 2.24 Ga Kazput Formation

    NASA Astrophysics Data System (ADS)

    Thoby, M.; Konhauser, K.; Philippot, P.; Killingsworth, B.; Warchola, T.; Lalonde, S.

    2017-12-01

    Following the Great Oxidation event (GOE) defined from 2.45 to 2.2 Ga, an event marking the first appearance of widespread atmospheric oxygen, a combination of decreased Mn(II) supply from land and increased Mn(IV)-precipitation in the oceans should have resulted in lower concentrations of Mn in seawater. Nevertheless, it appears that some early Proterozoic marine sediments record high seawater Mn concentrations hundreds of millions of years after the GOE. Here we investigate a Mn excursion associated with marine carbonates and shales of the 2.31 Ga Kazput Formation. Samples were recovered from drill core collected during the Turee Creek Drilling Project (TCDP). Using molybdenum (Mo) isotope data coupled with cerium (Ce) anomalies, we define the redox condition of the Kazput depositional environment. Initial results show no Mo fractionation and few cerium anomalies in carbonates, pointing to an anoxic basin without Mn oxide precipitates. Additionally, XRF data on the shales indicates an association of Mn with calcium (Ca) suggesting an anoxic environment at the time of their deposition. Our results provide new insights into the nature and environment of the Turee Creek basin and the extent of oxygenation of surface waters after the GOE.

  13. Loss of hfe function reverses impaired recognition memory caused by olfactory manganese exposure in mice.

    PubMed

    Ye, Qi; Kim, Jonghan

    2015-03-01

    Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout (Hfe (-/-)) and wild-type (Hfe (+/+)) mice mice were intranasally-instilled with manganese chloride (MnCl2 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in Hfe (+/+) mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, Hfe (-/-) mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in Hfe (+/+) mice, but not in Hfe (-/-) mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of

  14. Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

    PubMed Central

    Lim, Sanghee; Kwak, Minhye; Gray, Christy D.; Xu, Michael; Choi, Jun H.; Junn, Sue; Kim, Jieun; Xu, Jing; Schaefer, Michele; Johns, Roger A.; Song, Hongjun; Ming, Guo-Li; Mintz, C. David

    2017-01-01

    Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition. PMID:28683067

  15. The Educational Impact of Exposure to Clinical Psychiatry Early in an Undergraduate Medical Curriculum.

    PubMed

    Brown, Menna; Barnes, Jacob; Silver, Katie; Williams, Nicholas; Newton, Philip M

    2016-04-01

    The medical school at Swansea University provides compulsory early exposure to clinical education through short learning opportunities in the clinical setting (LOCS). These are 3-4-h sessions chosen by students from a list of over 900. Students are required to complete ten LOCS in each of their first 2 years of medical school, with at least one per year being in psychiatry. The objective of this study was to evaluate the educational experience of students undertaking LOCS in psychiatry, in part to understand whether this experience affects student understanding of psychiatry and the likelihood that they will pursue it as a career. A mixed methods approach was used. Qualitative focus group discussions were conducted with medical students to explore perceptions of psychiatry and experiences of psychiatry LOCS. Findings informed the development of a structured quantitative survey aimed at a larger sample of students. Six qualitative themes emerged: (1) limited exposure to psychiatry, (2) organizational issues, (3) positive LOCS experiences, (4) stigma, (5) anticipated emotional burden, (6) psychiatry at odds with current understanding of medicine. Questionnaire data showed that psychiatry is not a popular future career choice when compared to other specialties. Psychiatry LOCS are extremely popular with students and have a positive effect on their understanding of the specialty but did little to influence their stated likelihood of pursuing psychiatry as a career. Early exposure to clinical psychiatry through LOCS gives students positive experiences, which improve understanding and awareness of psychiatry. They do not, however, affect stated career intentions for psychiatry as a profession.

  16. Occupational pesticide exposure in early pregnancy associated with sex-specific neurobehavioral deficits in the children at school age.

    PubMed

    Andersen, Helle R; Debes, Fróði; Wohlfahrt-Veje, Christine; Murata, Katsuyuki; Grandjean, Philippe

    2015-01-01

    Prenatal exposure to pesticides may affect neurodevelopment, while the impact of modern pesticides is unclear. From 1997-2001, women working in greenhouse horticultures were recruited at the beginning of their pregnancy. Based on detailed interview of the women and their employers, those categorized as occupationally exposed to pesticides were moved to unexposed work functions or went on paid leave, while women without any exposure were considered unexposed controls. Of the resulting birth cohort of 203 children, 133 (65%) were examined at age 6 to 11 years together with 44 newly recruited children of same age whose mothers were not occupationally exposed to pesticides in pregnancy. All children underwent a standardized examination including a battery of neurodevelopmental tests. Maternal occupational pesticide exposure in early pregnancy was associated with prolonged brainstem auditory evoked potential latencies in the children as a whole and with impaired neuropsychological function in girls, while no effect was apparent in boys. In girls, language and motor speed functions were significantly inversely associated with prenatal exposure, and a non-significant tendency toward decreased function was also seen for other neuropsychological outcomes. A structural equation model that combined all these test results showed an overall impaired neuropsychological function in girls prenatally exposed to pesticides. Thus, our findings suggest an adverse effect of maternal occupational pesticide exposure on their children's neurodevelopment, despite the fact that the exposures occurred solely during early pregnancy and under well regulated working conditions, where special measures to protect pregnant women were applied. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Lead exposure and early child neurodevelopment among children 12-24 months in Kinshasa, the Democratic Republic of Congo.

    PubMed

    Kashala-Abotnes, Espérance; Mumbere, Pépé Penghele; Mishika, Jeannette Mukanya; Ndjukendi, Ally Omba; Mpaka, Davin Beya; Bumoko, Makila-Mabe Guy; Kayembe, Tharcisse Kalula; Tshala-Katumbay, Désiré; Kazadi, Théodore Kayembe; Okitundu, Daniel Luwa E-Andjafono

    2016-12-01

    Childhood lead exposure remains a problem in developing countries, and little is known about its effects on early child neurodevelopment and temperament in the Democratic Republic of Congo (DRC). We, therefore, conducted this study to determine the association between lead exposure and the neurodevelopment and behaviour of children aged 12-24 months in Kinshasa, DRC. A cross-sectional study was conducted between February and June 2012, and parents of 104 children were invited to participate. Blood lead levels (BLLs) of each child were tested using the flame atomic spectrophotometry method. All children were subject to a clinical examination and assessed with two selected early child neurodevelopmental tools, the Gensini-Gavito and the baby characteristics questionnaire, to measure their neurodevelopment and temperament. Detectable BLLs ranged from 1 to 30 μg/dl with a geometric mean of 6.9 (SD 4.8) μg/dl. BLLs at 5-9 and ≥10 μg/dl were significantly associated with the child temperament (p <0.05). Perinatal and maternal factors did not seem to affect early child neurodevelopment and temperament. Children exposed to lead were reported with more temperament difficulties at even blood lead levels <10 μg/dl, suggesting the need for preventive and intervention measures to reduce lead exposure among children in Kinshasa, DRC.

  18. Sense of coherence moderates late effects of early childhood Holocaust exposure.

    PubMed

    van der Hal-van Raalte, Elisheva A M; van IJzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

    2008-12-01

    This study evaluated child Holocaust survivors with an emphasis on potential protective factors facilitating participants' adaptation to post-Holocaust life. We examined Antonovsky's (1979, 1987) salutogenic paradigm, testing the mediating and moderating effect of participants' sense of coherence (SOC) on the association between early childhood deprivation due to Holocaust persecution and posttraumatic stress later in life. The nonclinical sample, composed of 203 child Holocaust survivors born between 1935 and 1944 completed questionnaires on Holocaust survival exposure, inventories on current health, posttraumatic stress, and SOC. The results indicated that SOC moderates the association between traumatic experiences during the war and posttraumatic stress, and SOC acts as a protective factor, buffering the impact of traumatic Holocaust experiences on child survivors in old age. Survivors with a less coherent perspective on the meaning of their life showed greater vulnerability for posttraumatic complaints. The moderating role of the SOC may suggest promising avenues of therapeutic interventions for child Holocaust survivors and other adults with early childhood trauma. (c) 2008 Wiley Periodicals, Inc.

  19. High-O2, low-CO2 atmosphere on early Mars inferred from manganese oxide deposits

    NASA Astrophysics Data System (ADS)

    Sekine, Y.; Imanura, S.; Noda, N.; Takahashi, Y.; Uesugi, S.; Kurisu, M.; Hartmann, J.

    2017-12-01

    The atmospheric composition and its redox state are central to understanding of geochemical cycles, aqueous environment, and habitability on early Mars. Findings of manganese (Mn) oxide deposits together with some trace metals (e.g., Zn and Ni) by the Curiosity and Opportunity rovers suggest a more oxidizing surface environments on early Mars, possibly with higher amount of O2, than in the present day [Lanza et al., 2016; Arvidson et al., 2016; Hurowitz et al., 2017]. However, the abundance and formation mechanism of O2 have been poorly constrained. In the present study, we report results of laboratory experiments to constrain the redox state of the aqueous environment and atmospheric composition responsible for formation of the Mn oxides on early Mars. Our results of scavenging pattern of trace metals show that the Mn oxides found by the rovers are MnO2, which requires highly oxidizing water (Eh > 0.4 V at pH 7-8) and high atmospheric O2 (> a few mbar) for deposition. We suggest that a low-CO2 condition are also required to prevent formation of Mn carbonate in the aqueous environments. We suggest a low CO2/O2 atmosphere, e.g., CO2/O2 < 1, on early Mars at the time of deposition. This in turn implies that O2 would not have been derived mainly from CO2 photolysis and may require more effective paths (e.g., H2O photolysis and effective atmospheric escape) for producing O2 in the very early stage of Mars' history.

  20. Tuning electronic and magnetic properties of Mn-mullite oxide sub-nanoclusters via MnOn polyhedron units.

    PubMed

    Li, Hui; Cho, Kyeongjae; Li, Shunfang; Wang, Weichao

    2018-06-13

    Ternary oxide nano-clusters compared to unary metallic and binary ones potentially exhibit more remarkable properties due to their higher stoichiometric flexibility in addition to cluster size variations. Herein, by combining with the structural searching scheme CALYPSO, we have built a series of Mn-mullite oxide clusters (SmxMnyOz)n {(xyz) = (125); (115); n = 1-4, 8} prior to investigation of their geometric and electronic structures via first-principles calculations. In small size regime (n < 4), (SmxMnyOz)n prefer nonstoichiometric (Sm1Mn1O5)n phases composed of nonmagnetic MnO4 tetrahedrons. When n ≧ 4, the clusters tend to develop as stoichiometric (Sm1Mn2O5)n species, including magnetic MnOn polyhedrons and Mn-Mn dimers, which contribute 3d-orbitals (dz2 and/or dx2-y2) around the Fermi levels. The different magnetic behaviors of nonstoichiometric and stoichiometric species originate from the distinct couplings of MnOn polyhedronal units, wherein Mn atoms experience different ligand fields and thus display different spin states. Such findings enable the tuning of electronic properties and potential applications in heterogeneous catalysis, electrochemical catalysis, and the related fields via engineering cluster size and stoichiometry.

  1. Antiferromagnetism in semiconducting SrMn 2 Sb 2 and BaMn 2 Sb 2 single crystals

    DOE PAGES

    Sangeetha, N. S.; Smetana, V.; Mudring, A. -V.; ...

    2018-01-03

    Here, crystals of SrMn 2Sb 2 and BaMn 2Sb 2 were grown using Sn flux and characterized by powder and single-crystal x-ray diffraction, respectively, and by single-crystal electrical resistivity ρ, heat capacity C p, and magnetic susceptibility χ measurements versus temperature T, and magnetization versus field M(H) isotherm measurements. SrMn 2Sb 2 adopts the trigonal CaAl 2Si 2-type structure, whereas BaMn 2Sb 2 crystallizes in the tetragonal ThCr 2Si 2-type structure. The ρ(T) data indicate semiconducting behaviors for both compounds with activation energies of ≳0.35 eV for SrMn 2Sb 2 and 0.16 eV for BaMn 2Sb 2. The χ(T) andmore » C p(T) data reveal antiferromagnetic (AFM) ordering at T N = 110 K for SrMn 2Sb 2 and 450 K for BaMn 2Sb 2. The anisotropic χ(T≤T N) data also show that the ordered moments in SrMn 2Sb 2 are aligned in the hexagonal ab plane, whereas the ordered moments in BaMn 2Sb 2 are aligned collinearly along the tetragonal c axis. The ab-plane M(H) data for SrMn 2Sb 2 exhibit a continuous metamagnetic transition at low fields 02Sb 2 exhibits no metamagnetic transitions up to 5.5 T. The χ(T) and C p(T) data for both SrMn 2Sb 2 and BaMn 2Sb 2 indicate strong dynamic short-range AFM correlations above their respective T N up to at least 900 K within a local-moment picture, corresponding to quasi-two-dimensional magnetic behavior. The present results and a survey of the literature for Mn pnictides with the CaAl 2Si 2 and ThCr 2Si 2 crystal structures show that the T N values for the CaAl 2Si 2-type compounds are much smaller than those for the ThCr 2Si 2-type materials.« less

  2. Irradiated esophageal cells are protected from radiation-induced recombination by MnSOD gene therapy.

    PubMed

    Niu, Yunyun; Wang, Hong; Wiktor-Brown, Dominika; Rugo, Rebecca; Shen, Hongmei; Huq, M Saiful; Engelward, Bevin; Epperly, Michael; Greenberger, Joel S

    2010-04-01

    Radiation-induced DNA damage is a precursor to mutagenesis and cytotoxicity. During radiotherapy, exposure of healthy tissues can lead to severe side effects. We explored the potential of mitochondrial SOD (MnSOD) gene therapy to protect esophageal, pancreatic and bone marrow cells from radiation-induced genomic instability. Specifically, we measured the frequency of homologous recombination (HR) at an integrated transgene in the Fluorescent Yellow Direct Repeat (FYDR) mice, in which an HR event can give rise to a fluorescent signal. Mitochondrial SOD plasmid/liposome complex (MnSOD-PL) was administered to esophageal cells 24 h prior to 29 Gy upper-body irradiation. Single cell suspensions from FYDR, positive control FYDR-REC, and negative control C57BL/6NHsd (wild-type) mouse esophagus, pancreas and bone marrow were evaluated by flow cytometry. Radiation induced a statistically significant increase in HR 7 days after irradiation compared to unirradiated FYDR mice. MnSOD-PL significantly reduced the induction of HR by radiation at day 7 and also reduced the level of HR in the pancreas. Irradiation of the femur and tibial marrow with 8 Gy also induced a significant increase in HR at 7 days. Radioprotection by intraesophageal administration of MnSOD-PL was correlated with a reduced level of radiation-induced HR in esophageal cells. These results demonstrate the efficacy of MnSOD-PL for suppressing radiation-induced HR in vivo.

  3. Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice.

    PubMed

    Wieczorek, Lindsay; Fish, Eric W; O'Leary-Moore, Shonagh K; Parnell, Scott E; Sulik, Kathleen K

    2015-05-01

    The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Early Exposure to Stimulant Medications and Substance-Related Problems: The Role of Medical and Nonmedical Contexts

    PubMed Central

    McCabe, Sean Esteban; Veliz, Phil; Boyd, Carol J.

    2016-01-01

    Background The age of onset (early vs. late) and context (medical vs. nonmedical) of exposure to stimulant medications for attention-deficit/hyperactivity disorder (ADHD) have been identified as important factors in the addictive potential of these controlled medications. This study examines the role of medical and nonmedical contexts in the association between early exposure to stimulant medications and substance use and substance-related problems among adolescents. Methods A Web-based survey was self-administered by Detroit-area secondary school students (N = 4,755) between the 2009–10 and 2012–13 school years. The sample consisted of 51% females, 62% Whites, 32% African-Americans, and 6% from other racial categories. Results During the study period, an estimated 11.7% of respondents were ever diagnosed with ADHD. Approximately 6.7% (n = 322) of respondents indicated lifetime medical use of prescription stimulants while 2.6% (n = 124) indicated lifetime nonmedical use. The odds of substance use and substance-related problems were significantly lower among those who initiated earlier medical use of stimulant medications relative to later medical initiation. In contrast, the odds of substance use and substance-related problems were significantly greater among those who initiated earlier nonmedical use of stimulant medications relative to later nonmedical initiation. Conclusions More than one in every ten adolescents in this epidemiologically-derived community-based sample was diagnosed with ADHD. This is the first investigation to demonstrate that context (medical vs. nonmedical) plays a critical role in the relationship between early exposure to stimulant medications and the subsequent risk of substance-related problems during adolescence within the same diverse youth sample. PMID:27129621

  5. Association of Prenatal and Early Life Exposure to Tetrachloroethylene (PCE) with Polycystic Ovary Syndrome and Other Reproductive Disorders in the Cape Cod Health Study: A Retrospective Cohort Study

    PubMed Central

    Mahalingaiah, Shruthi; Winter, Michael R.; Aschengrau, Ann

    2016-01-01

    Background Tetrachloroethylene (PCE) is an organic lipophilic solvent with possible neuroendocrine toxicity. The objective of this study was to determine the association of prenatal and early childhood exposure to PCE-contaminated drinking water and development of adult-onset Polycystic Ovary Syndrome (PCOS), endometriosis, difficulty conceiving and miscarriage. Methods Five-hundred exposed and 331 unexposed female participants born between 1969 and 1983 completed questionnaires on demographic and lifestyle characteristics, and reproductive disorders. Residential locations from the prenatal period through five years of age were used to estimate early life PCE exposure with water modeling software. Results For any early life exposure to PCE, the adjusted risk ratio for PCOS was 0.9 (95% CI: 0.5–1.6). No statistically significant associations were observed for increasing levels of exposure with PCOS or the other reproductive disorders. Conclusion No meaningful associations were found among adult women with early life exposure to PCE-contaminated drinking water and adult-onset reproductive disorders. PMID:27412368

  6. Local structure in LaMnO3 and CaMnO3 perovskites: A quantitative structural refinement of Mn K -edge XANES data

    NASA Astrophysics Data System (ADS)

    Monesi, C.; Meneghini, C.; Bardelli, F.; Benfatto, M.; Mobilio, S.; Manju, U.; Sarma, D. D.

    2005-11-01

    Hole-doped perovskites such as La1-xCaxMnO3 present special magnetic and magnetotransport properties, and it is commonly accepted that the local atomic structure around Mn ions plays a crucial role in determining these peculiar features. Therefore experimental techniques directly probing the local atomic structure, like x-ray absorption spectroscopy (XAS), have been widely exploited to deeply understand the physics of these compounds. Quantitative XAS analysis usually concerns the extended region [extended x-ray absorption fine structure (EXAFS)] of the absorption spectra. The near-edge region [x-ray absorption near-edge spectroscopy (XANES)] of XAS spectra can provide detailed complementary information on the electronic structure and local atomic topology around the absorber. However, the complexity of the XANES analysis usually prevents a quantitative understanding of the data. This work exploits the recently developed MXAN code to achieve a quantitative structural refinement of the Mn K -edge XANES of LaMnO3 and CaMnO3 compounds; they are the end compounds of the doped manganite series LaxCa1-xMnO3 . The results derived from the EXAFS and XANES analyses are in good agreement, demonstrating that a quantitative picture of the local structure can be obtained from XANES in these crystalline compounds. Moreover, the quantitative XANES analysis provides topological information not directly achievable from EXAFS data analysis. This work demonstrates that combining the analysis of extended and near-edge regions of Mn K -edge XAS spectra could provide a complete and accurate description of Mn local atomic environment in these compounds.

  7. Chronic ethanol exposure during adolescence through early adulthood in female rats induces emotional and memory deficits associated with morphological and molecular alterations in hippocampus.

    PubMed

    Oliveira, Ana Ca; Pereira, Maria Cs; Santana, Luana N da Silva; Fernandes, Rafael M; Teixeira, Francisco B; Oliveira, Gedeão B; Fernandes, Luanna Mp; Fontes-Júnior, Enéas A; Prediger, Rui D; Crespo-López, Maria E; Gomes-Leal, Walace; Lima, Rafael R; Maia, Cristiane do Socorro Ferraz

    2015-06-01

    There is increasing evidence that heavy ethanol exposure in early life may produce long-lasting neurobehavioral consequences, since brain structural maturation continues until adolescence. It is well established that females are more susceptible to alcohol-induced neurotoxicity and that ethanol consumption is increasing among women, especially during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence through early adulthood in female rats may induce hippocampal histological damage and neurobehavioral impairments. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) by gavage from the 35(th)-90(th) day of life. Ethanol-exposed animals displayed reduced exploration of the central area and increased number of fecal boluses in the open field test indicative of anxiogenic responses. Moreover, chronic high ethanol exposure during adolescence induced marked impairments on short-term memory of female rats addressed on social recognition and step-down inhibitory avoidance tasks. These neurobehavioral deficits induced by ethanol exposure during adolescence through early adulthood were accompanied by the reduction of hippocampal formation volume as well as the loss of neurons, astrocytes and microglia cells in the hippocampus. These results indicate that chronic high ethanol exposure during adolescence through early adulthood in female rats induces long-lasting emotional and memory deficits associated with morphological and molecular alterations in the hippocampus. © The Author(s) 2015.

  8. Neuropsychological Motor Outcomes in Adults from Airborne Manganese Exposure

    EPA Science Inventory

    Background: The literature on manganese (Mn) is dominated by occupational exposures of adults exposed often to high levels without protection. Neuropsychological adverse health effects are similar to Parkinson’s Disease with psychomotor slowing, tremor, cognitive and mood ...

  9. Environmental exposures of trace elements assessed using keratinized matrices from patients with chronic kidney diseases of uncertain etiology (CKDu) in Sri Lanka.

    PubMed

    Diyabalanage, Saranga; Fonseka, Sanjeewani; Dasanayake, D M S N B; Chandrajith, Rohana

    2017-01-01

    An alarming increase in chronic kidney disease with unknown etiology (CKDu) has recently been reported in several provinces in Sri Lanka and chronic exposures to toxic trace elements were blamed for the etiology of this disease. Keratinized matrices such as hair and nails were investigated to determine the possible link between CKDu and toxic element exposures. Elements Li, B, Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Cd, Ba, Hg and Pb of hair and nails of patients and age that matched healthy controls were determined with Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The results showed that trace element contents in the hair of patients varies in the order of Zn>Fe>Al>Mn>Cu>Ba>Sr>Ni>Pb>Cr>B>Hg>Se>Mo>Co>As>Li>Cd while Fe>Al>Zn>Ni>Cu>Mn>Cr>Ba>Sr>B>Pb>Se>Mo>Co>Hg>Li>As>Cd in nail samples. The hair As levels of 0.007-0.165μgg -1 were found in CKDu subjects. However, no significant difference was observed between cases and controls. The total Se content in hair of CKDu subjects ranged from 0.043 to 0.513μgg -1 while it was varied from 0.031 to 1.15μgg -1 in controls. Selenium in nail samples varied from 0.037μgg -1 to 4.10μgg -1 in CKDu subjects and from 0.042μgg -1 to 2.19μgg -1 in controls. This study implies that substantial proportions of Sri Lankan population are Se deficient irrespective of gender, age and occupational exposure. Although some cutaneous manifestations were observed in patient subjects, chemical analyses of hair and nails indicated that patients were not exposed to toxic levels of arsenic or the other studied toxic elements. Therefore the early suggested causative factors such as exposure to environmental As and Cd, can be ruled out. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. A comparison of functional magnetic resonance imaging findings in children with and without a history of early exposure to general anesthesia.

    PubMed

    Taghon, Thomas A; Masunga, Abigail N; Small, Robert H; Kashou, Nasser H

    2015-03-01

    Functional magnetic resonance imaging (fMRI) has been used to evaluate the long-term consequences of early exposure to neurotoxic agents. fMRI shows that different patterns of brain activation occur in ethanol-exposed subjects performing a go/no-go response inhibition task. Pharmacologically, ethanol and general anesthetics have similar receptor-level activity in the brain. This study utilizes fMRI to examine brain activation patterns in children exposed to general anesthesia and surgery during early brain development. After obtaining Nationwide Children's Hospital IRB approval, a surgical database was utilized to identify children aged 10-17 years with a history of at least 1 h of exposure to general anesthetics and surgery when they were between 0 and 24 months of age. Age- and gender-matched children without anesthesia exposure were recruited as a control group. All subjects were scanned while being presented with a go/no-go response inhibition task. Reaction time and accuracy data were acquired, and the blood-oxygen-level-dependent (BOLD) fMRI signal was measured as a biomarker for regional neuronal activity. There were no differences in terms of performance accuracy and response time. The analysis did not reveal any significant activation differences in the primary region of interest (prefrontal cortex and caudate nucleus); however, activation differences were seen in other structures, including the cerebellum, cingulate gyrus, and paracentral lobule. Early anesthetic exposure and surgery did not affect accuracy, response time, or activation patterns in the primary region of interest during performance of the task. Intergroup differences in activation patterns in other areas of the brain were observed, and the significance of these findings is unknown. fMRI appears to be a useful tool in evaluating the long-term effects of early exposure to general anesthesia. © 2015 John Wiley & Sons Ltd.

  11. CaMn 2Al 10: Itinerant Mn magnetism on the verge of magnetic order

    DOE PAGES

    Steinke, L.; Simonson, J. W.; Yin, W. -G.; ...

    2015-07-24

    We report the discovery of CaMn 2Al 10, a metal with strong magnetic anisotropy and moderate electronic correlations. Magnetization measurements find a Curie-Weiss moment of 0.83 μB/Mn, significantly reduced from the Hund's rule value, and the magnetic entropy obtained from specific heat measurements is correspondingly small, only ≈ 9% of Rln2. These results imply that the Mn magnetism is highly itinerant, a conclusion supported by density functional theory calculations that find strong Mn-Al hybridization. Consistent with the layered nature of the crystal structure, the magnetic susceptibility χ is anisotropic below 20 K, with a maximum ratio of χ [010]/χ [001]more » ≈ 3.5. A strong power-law divergence χ(T) ~ T –1.2 below 20 K implies incipient ferromagnetic order, an Arrott plot analysis of the magnetization suggests a vanishing low Curie temperature T C ~ 0. Our experiments indicate that CaMn 2Al 10 is a rare example of a system where the weak and itinerant Mn-based magnetism is poised on the verge of order.« less

  12. Early and sustained exposure to high-sucrose diet triggers hippocampal ER stress in young rats.

    PubMed

    Pinto, Bruno Araújo Serra; Melo, Thamys Marinho; Flister, Karla Frida Torres; França, Lucas Martins; Kajihara, Daniela; Tanaka, Leonardo Yuji; Laurindo, Francisco Rafael Martins; Paes, Antonio Marcus de Andrade

    2016-08-01

    Early-life environmental insults have been shown to promote long-term development of chronic non-communicable diseases, including metabolic disturbances and mental illnesses. As such, premature consumption of high-sugar foods has been associated to early onset of detrimental outcomes, whereas underlying mechanisms are still poorly understood. In the present study, we sought to investigate whether early and sustained exposure to high-sucrose diet promotes metabolic disturbances that ultimately might anticipate neurological injuries. At postnatal day 21, weaned male rats started to be fed a standard chow (10 % sucrose, CTR) or a high-sucrose diet (25 % sucrose, HSD) for 9 weeks prior to euthanasia at postnatal day 90. HSD did not alter weight gain and feed efficiency between groups, but increased visceral, non-visceral and brown adipose tissue accumulation. HSD rats demonstrated elevated blood glucose levels in both fasting and fed states, which were associated to impaired glucose tolerance. Peripheral insulin sensitivity did not change, whereas hepatic insulin resistance was supported by increased serum triglyceride levels, as well as higher TyG index values. Assessment of hippocampal gene expression showed endoplasmic reticulum (ER) stress pathways were activated in HSD rats, as compared to CTR. HSD rats had overexpression of unfolded protein response sensors, PERK and ATF6; ER chaperone, PDIA2 and apoptosis-related genes, CHOP and Caspase 3; but decreased expression of chaperone GRP78. Finally, HSD rats demonstrated impaired neuromuscular function and anxious behavior, but preserved cognitive parameters. In conclusion, our data indicate that early exposure to HSD promote metabolic disturbances, which disrupt hippocampus homeostasis and might precociously affect its neurobehavioral functions.

  13. Maternal exposure to metals—Concentrations and predictors of exposure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Callan, A.C., E-mail: a.callan@ecu.edu.au; Hinwood, A.L.; Ramalingam, M.

    2013-10-15

    A variety of metals are important for biological function but have also been shown to impact health at elevated concentrations, whereas others have no known biological function. Pregnant women are a vulnerable population and measures to reduce exposure in this group are important. We undertook a study of maternal exposure to the metals, aluminium, arsenic, copper, cobalt, chromium, lithium, manganese, nickel, selenium, tin, uranium and zinc in 173 participants across Western Australia. Each participant provided a whole blood and urine sample, as well as drinking water, residential soil and dust samples and completed a questionnaire. In general the concentrations ofmore » metals in all samples were low with the notable exception of uranium (blood U mean 0.07 µg/L, range <0.01–0.25 µg/L; urinary U mean 0.018 µg/g creatinine, range <0.01–0.199 µg/g creatinine). Factors that influenced biological concentrations were consumption of fish which increased urinary arsenic concentrations, hobbies (including mechanics and welding) which increased blood manganese concentrations and iron/folic acid supplement use which was associated with decreased concentrations of aluminium and nickel in urine and manganese in blood. Environmental concentrations of aluminium, copper and lithium were found to influence biological concentrations, but this was not the case for other environmental metals concentrations. Further work is underway to explore the influence of diet on biological metals concentrations in more detail. The high concentrations of uranium require further investigation. -- Highlights: • High concentrations of uranium with respect to international literature. • Environmental concentrations of Al, Cu and Li influenced urinary concentrations. • Exposure to mechanics/welding hobbies increased blood Mn concentrations. • Iron/Folic acid supplements reduced biological concentrations of Al, Ni and Mn.« less

  14. Elevated manganese exposure and school-aged children's behavior: a gender-stratified analysis.

    PubMed

    Menezes-Filho, José A; de Carvalho-Vivas, Chrissie F; Viana, Gustavo F S; Ferreira, Junia R D; Nunes, Lorena S; Mergler, Donna; Abreu, Neander

    2014-12-01

    High levels of waterborne manganese have been associated with problematic behavior in school-aged children, however to date this has not been reported for children exposed to airborne manganese. The objective of the present study was to examine behavioral traits among children with exposure to airborne manganese from a ferro-manganese alloy plant, located in the metropolitan region of Salvador, Brazil. The study included 34 boys and 36 girls, aged 7-12 years, living in two communities within a 3-km radius from the plant. For each child, hair manganese levels (MnH) and blood lead (PbB) levels were analyzed by graphite furnace atomic absorption spectrometry. The Children's Behavior Check List (CBCL) (Portuguese version validated in Brazil) was administered to parents or caregivers, providing scale scores of internalizing (withdrawn, somatic complaints, and anxious/depressed scales), externalizing (disruptive and aggressive) behaviors and a separate scale for attention problems. Median and range for MnH and PbB were 11.48 μg/g (range: 0.52-55.74); 1.1 μg/dL (range: 0.5-6.1), respectively. Spearman correlation analyses showed that several behavioral indices were significantly correlated with MnH levels for girls, but not for boys: total externalizing behavior (rho=0.484 vs rho=0.041) and attention problem scores (rho=0.542 vs rho=0.003) coefficients were significantly at p<0.001 level, respectively for girls and boys. No significant correlation was observed with any of the internalizing sub-scales. A linear regression model was fitted with the total externalizing behavior, inattention and total CBCL scores as dependent variables, with log transformed MnH stratified by sex, adjusting for age and maternal IQ. Total externalizing behaviors and attention problem scores were significantly associated with girls' MnH levels but not with boys'. Adjusting for maternal IQ, the β-coefficients for LogMnH associations with total externalizing and attention problems are 8.85 (95

  15. A binuclear Mn(III) complex of a scorpiand-like ligand displaying a single unsupported Mn(III)-O-Mn(III) bridge.

    PubMed

    Blasco, Salvador; Cano, Joan; Clares, M Paz; García-Granda, Santiago; Doménech, Antonio; Jiménez, Hermas R; Verdejo, Begoña; Lloret, Francesc; García-España, Enrique

    2012-11-05

    The crystal structure of a binuclear Mn(III) complex of a scorpiand-like ligand (L) displays an unsupported single oxo bridging ligand with a Mn(III)-O-Mn(III) angle of 174.7°. Magnetic susceptibility measurements indicate strong antiferromagnetic coupling between the two metal centers. DFT calculations have been carried out to understand the magnetic behavior and to analyze the nature of the observed Jahn-Teller distortion. Paramagnetic (1)H NMR has been applied to rationalize the formation and magnetic features of the complexes formed in solution.

  16. Zn-Mn alloy coatings from acidic chloride bath: Effect of deposition conditions on the Zn-Mn electrodeposition-morphological and structural characterization

    NASA Astrophysics Data System (ADS)

    Loukil, N.; Feki, M.

    2017-07-01

    Zn-Mn alloy electrodeposition on steel electrode in chloride bath was investigated using cyclic voltammetric, chronopotentiometric and chronoamperometric techniques. Cyclic voltammetries (CV) reveal a deep understanding of electrochemical behaviors of each metal Zn, Mn, proton discharge and Zn-Mn co-deposition. The electrochemical results show that with increasing Mn2+ ions concentration in the electrolytic bath, Mn2+ reduction occurs at lower over-potential leading to an enhancement of Mn content into the Zn-Mn deposits. A dimensionless graph model was used to analyze the effect of Mn2+ ions concentration on Zn-Mn nucleation process. It was found that the nucleation process is not extremely affected by Mn2+ concentration. Nevertheless, it significantly depends on the applied potential. Several parameters such as Mn2+ ions concentration, current density and stirring were investigated with regard to the Mn content into the final Zn-Mn coatings. It was found that the Mn content increases with increasing the applied current density jimp and Mn2+ ions concentration in the electrolytic bath. However, stirring of the solution decreases the Mn content in the Zn-Mn coatings. The phase structure and surface morphology of Zn-Mn deposits are characterized by means of X-ray diffraction analysis and Scanning Electron Microscopy (SEM), respectively. The Zn-Mn deposited at low current density is tri-phasic and consisting of η-Zn, ζ-MnZn13 and hexagonal close packed ε-Zn-Mn. An increase in current density leads to a transition from crystalline to amorphous structure, arising from the hydroxide inclusions in the Zn-Mn coating at high current density.

  17. Early age exposure to moisture damage and systemic inflammation at the age of 6 years.

    PubMed

    Karvonen, A M; Tischer, C; Kirjavainen, P V; Roponen, M; Hyvärinen, A; Illi, S; Mustonen, K; Pfefferle, P I; Renz, H; Remes, S; Schaub, B; von Mutius, E; Pekkanen, J

    2018-05-01

    Cross-sectional studies have shown that exposure to indoor moisture damage and mold may be associated with subclinical inflammation. Our aim was to determine whether early age exposure to moisture damage or mold is prospectively associated with subclinical systemic inflammation or with immune responsiveness in later childhood. Home inspections were performed in children's homes in the first year of life. At age 6 years, subclinical systemic inflammation was measured by serum C-reactive protein (CRP) and blood leukocytes and immune responsiveness by ex vivo production of interleukin 1-beta (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) in whole blood cultures without stimulation or after 24 hours stimulation with phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG) in 251-270 children. Moisture damage in child's main living areas in infancy was not significantly associated with elevated levels of CRP or leukocytes at 6 years. In contrast, there was some suggestion for an effect on immune responsiveness, as moisture damage with visible mold was positively associated with LPS-stimulated production of TNF-α and minor moisture damage was inversely associated with PI-stimulated IL-1β. While early life exposure to mold damage may have some influence on later immune responsiveness, it does not seem to increase subclinical systemic inflammation in later life. © 2018 National Institute for Health and Welfare, Finland Indoor Air published by John Wiley & Sons Ltd.

  18. Enhanced Cycleability of Amorphous MnO2 by Covering on α-MnO2 Needles in an Electrochemical Capacitor

    PubMed Central

    Liu, Quanbing; Yang, Juan; Wang, Hui; Pollet, Bruno G.; Wang, Rongfang

    2017-01-01

    An allomorph MnO2@MnO2 core-shell nanostructure was developed via a two-step aqueous reaction method. The data analysis of Scanning Electron Microscopy, Transmission Electron Microscopy, X-Ray Diffraction and N2 adsorption-desorption isotherms experiments indicated that this unique architecture consisted of a porous layer of amorphous-MnO2 nano-sheets which were well grown onto the surface of α-MnO2 nano-needles. Cyclic voltammetry experiments revealed that the double-layer charging and Faradaic pseudo-capacity of the MnO2@MnO2 capacitor electrode contributed to a specific capacitance of 150.3 F·g−1 at a current density of 0.1 A·g−1. Long cycle life experiments on the as-prepared MnO2@MnO2 sample showed nearly a 99.3% retention after 5000 cycles at a current density of 2 A·g−1. This retention value was found to be significantly higher than those reported for amorphous MnO2-based capacitor electrodes. It was also found that the remarkable cycleability of the MnO2@MnO2 was due to the supporting role of α-MnO2 nano-needle core and the outer amorphous MnO2 layer. PMID:28837099

  19. Structure and magnetic properties of L10-MnGa nanoparticles prepared using direct reactions between Mn nanoparticles and Ga

    NASA Astrophysics Data System (ADS)

    Si, P. Z.; Qian, H. D.; Park, J.; Ge, H. L.; Shinde, K. P.; Chung, K. C.; Choi, C. J.

    2018-05-01

    The tetragonal L10-Mn1+xGa (x<0.8) nanoparticles and bcc-Mn23Ga77 nanoparticles with large coercivity were prepared using direct reactions between Mn nanoparticles and Ga at elevated temperatures. The Mn23Ga77 phase was formed at ˜573 K while the L10-structured Mn1+xGa was formed at ˜850 K. After ball-milling, the L10-Mn1+xGa nanoparticles transformed into nano-flakes with enhanced coercivity. The size of the as-prepared Mn23Ga77 nanoparticles is comparable to that of the precursor Mn nanoparticles. An aggregation of the nanoparticles and thus a larger particle size were observed in the L10-Mn1+xGa nanoparticles obtained at 850 K. The size of the L10-Mn1+xGa nano-flakes is reduced to about 200-400 nm with a thickness of ˜20 nm. The coercivity of the Mn23Ga77 nanoparticles and the L10-Mn1+xGa nanoparticles at 300 K reached up to 0.2 T and 0.43 T, respectively. The coercivity of L10-Mn1+xGa ball-milled nano-flakes is 0.59 T at 300 K.

  20. Chronic Exposure to Bisphenol A Affects Uterine Function During Early Pregnancy in Mice

    PubMed Central

    Davila, Juanmahel; Kannan, Athilakshmi; Flaws, Jodi A.; Bagchi, Milan K.

    2016-01-01

    Environmental and occupational exposure to bisphenol A (BPA), a chemical widely used in polycarbonate plastics and epoxy resins, has received much attention in female reproductive health due to its widespread toxic effects. Although BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In this study, we addressed the effect of prolonged exposure to an environmental relevant dose of BPA on embryo implantation and establishment of pregnancy. Our studies revealed that treatment of mice with BPA led to improper endometrial epithelial and stromal functions thus affecting embryo implantation and establishment of pregnancy. Upon further analyses, we found that the expression of progesterone receptor (PGR) and its downstream target gene, HAND2 (heart and neural crest derivatives expressed 2), was markedly suppressed in BPA-exposed uterine tissues. Previous studies have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor and the MAPK signaling pathways and inhibiting epithelial proliferation. Interestingly, we observed that down-regulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with enhanced activation of fibroblast growth factor and MAPK signaling in the epithelium, thus contributing to aberrant proliferation and lack of uterine receptivity. Further, the differentiation of endometrial stromal cells to decidual cells, an event critical for the establishment and maintenance of pregnancy, was severely compromised in response to BPA. In summary, our studies revealed that chronic exposure to BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy. PMID:27022677

  1. Mn 4+ emission in pyrochlore oxides

    DOE PAGES

    Du, Mao-Hua

    2014-08-27

    For the existing Mn 4+ activated red phosphors have relatively low emission energies (or long emission wavelengths) and are therefore inefficient for general lighting. Density functional calculations are performed to study Mn 4+ emission in rare-earth hafnate, zirconate, and stannate pyrochlore oxides (RE 2Hf 2O 7, RE 2Zr 2O 7, and RE 2Sn 2O 7). We show how the different sizes of the RE 3+ cation in these pyrochlores affect the local structure of the distorted MnO 6 octahedron, the Mn–O hybridization, and the Mn 4+ emission energy. The Mn 4+ emission energies of many pyrochlores are found to bemore » higher than those currently known for Mn 4+ doped oxides and should be closer to that of Y 2O 3:Eu 3+ (the current commercial red phosphor for fluorescent lighting). The O–Mn–O bond angle distortion in a MnO6 octahedron is shown to play an important role in weakening Mn–O hybridization and consequently increasing the Mn 4+ emission energy. Our result shows that searching for materials that allow significant O–Mn–O bond angle distortion in a MnO 6 octahedron is an effective approach to find new Mn 4+ activated red phosphors with potential to replace the relatively expensive Y 2O 3:Eu 3+ phosphor.« less

  2. Manganese and Mn/Ca ratios in soil and vegetation in forests across the northeastern US: Insights on spatial Mn enrichment.

    PubMed

    Richardson, J B

    2017-03-01

    Manganese (Mn) cycling in the Critical Zone is important because of its role as an essential nutrient and potential toxicity to plants and organisms. Quantifying Mn enrichment in terrestrial environments has been limited since Mn is monoisotopic. However, elemental ratios of Mn/Ca ratios may be used to determine spatial Mn enrichment and in aboveground and belowground pools. The objectives of this study were to quantify the spatial variation in Mn concentrations and Mn/Ca ratios in foliage, bolewood, forest floor, and mineral soil horizons across the northeastern United States and compare Mn/Ca ratios to estimate enrichment. Forest floor and mineral soil samples were collected from 26 study sites across the northeastern United States and analyzed by strong acid digestion. Foliage and bolewood was collected from 12 of the 26 sites and analyzed for total Mn and Ca. Our results show forest floor and mineral soil horizon Mn concentrations and Mn/Ca ratios were higher at Pennsylvania and New York sites than New Hampshire and Vermont sites. Using a modified isotope equation, enrichment factors (EF) for Mn/Ca ratios were calculated to be ~3.6 in the forest floor, upper and lower mineral soil horizons at sites in New York and Pennsylvania compared to reference sites in New Hampshire and Vermont. Foliar and bolewood Mn concentrations also decreased from Pennsylvania towards New Hampshire. Moreover, foliar and bolewood Mn concentrations were strongly correlated to forest floor, upper, and lower mineral soil Mn concentrations. It was hypothesized that internal cycling (uptake, throughfall, and litterfall) of Mn controls retention of enriched Mn in forests. Geologic influences from a lithologic gradient and soil pH gradient could also influence Mn enrichment in addition to Mn pollution. Ratios of Mn/Ca and other elemental ratios hold promise as geochemical tracers but require further development. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. The Impact of Early Medical School Surgical Exposure on Interest in Neurosurgery.

    PubMed

    Zuccato, Jeffrey A; Kulkarni, Abhaya V

    2016-05-01

    Medical student interest in neurosurgery is decreasing and resident attrition is trending upwards in favor of more lifestyle-friendly specialties that receive greater exposure during medical school. The University of Toronto began offering an annual two week comprehensive, focused surgical experience (Surgical Exploration and Discovery (SEAD) program) to 20 first year medical students increasing exposure to surgical careers. This study determines how SEAD affects students' views of a career in neurosurgery. Surveys were administered to 38 SEAD participants over two program cycles. Information was obtained regarding demographics, impacts of SEAD, and factors affecting career decision making. Subgroup analyses assessed for factors predicting pre- and post-intervention interest in neurosurgery. Ninety-seven percent (n=37) of students completed the survey. Before SEAD, 25% were interested in neurosurgery but this decreased to 10% post-SEAD (p=0.001). However, post-SEAD interest increased from 10% to 38% if lifestyle factors were theoretically controlled across surgical specialties (p<0.005). A majority (81%) felt SEAD improved their understanding of neurosurgery, 62.2% felt that exposure to other surgical specialties reduced their interest in neurosurgery, and 21% felt SEAD increased their interest in neurosurgery. Nineteen percent intended to explore neurosurgery further with observerships and one student planned to organize neurosurgical research. This surgical exposure intervention increased understanding about neurosurgery and reduced overall interest in neurosurgery as a career. However, those remaining interested were motivated to plan further neurosurgical clinical experiences. The SEAD program may, therefore, aid in early selection of students motivated to satisfy the demands of a neurosurgical career.

  4. Operando identification of the point of [Mn- 2]O- 4 spinel formation during gamma-MnO 2 discharge within batteries

    DOE PAGES

    Gallaway, Joshua W.; Hertzberg, Benjamin J.; Zhong, Zhong; ...

    2016-05-07

    The rechargeability of γ-MnO 2 cathodes in alkaline batteries is limited by the formation of the [Mn 2]O 4 spinels ZnMn 2O 4 (hetaerolite) and Mn 3O 4 (hausmannite). However, the time and formation mechanisms of these spinels are not well understood. Here we directly observe γ-MnO 2 discharge at a range of reaction extents distributed across a thick porous electrode. Coupled with a battery model, this reveals that spinel formation occurs at a precise and predictable point in the reaction, regardless of reaction rate. Observation is accomplished by energy dispersive X-ray diffraction (EDXRD) using photons of high energy andmore » high flux, which penetrate the cell and provide diffraction data as a function of location and time. After insertion of 0.79 protons per γ-MnO 2 the α-MnOOH phase forms rapidly. α-MnOOH is the precursor to spinel, which closely follows. ZnMn 2O 4 and Mn 3O 4 form at the same discharge depth, by the same mechanism. The results show the final discharge product, Mn 3O 4 or Mn(OH) 2, is not an intrinsic property of γ-MnO 2. While several studies have identified Mn(OH) 2 as the final γ-MnO 2 discharge product, we observe direct conversion to Mn 3O 4 with no Mn(OH) 2.« less

  5. Impact of early developmental fluoride exposure on the peripheral pain sensitivity in mice.

    PubMed

    Ma, Jing; Liu, Fei; Liu, Peng; Dong, Ying-Ying; Chu, Zheng; Hou, Tie-Zhou; Dang, Yong-Hui

    2015-12-01

    Consumption of high concentration of fluoride in the drinking water would cause the fluorosis and chronic pain. Similar pain syndrome appeared in the patients in fluoride therapy of osteoporotic. The aim of the current study was to examine whether exposing immature mice to fluoride would modify the peripheral pain sensitivity or even cause a pain syndrome. We gave developmental fluoride exposure to mice in different concentration (0mg/L, 50mg/L and 100mg/L) and evaluated their basal pain threshold. Von Frey hair test, hot plate test and formalin test were conducted to examine the mechanical, thermal nociceptive threshold and inflammatory pain, respectively. In addition, the expression of hippocampal brain-derived neurotrophic factor (BDNF) was also evaluated by Western blotting. Hyperalgesia in fluoride exposure mice was exhibited in the Von Frey hair test, hot plate test and formalin test. Meanwhile, the expression of BDNF was significantly higher than that of control group. The results suggest that early developmental fluoride exposure may lower the basal pain threshold and be associated with the increasing of BDNF expression in hippocampus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Resonant optical alignment and orientation of Mn2+ spins in CdMnTe crystals

    NASA Astrophysics Data System (ADS)

    Baryshnikov, K. A.; Langer, L.; Akimov, I. A.; Korenev, V. L.; Kusrayev, Yu. G.; Averkiev, N. S.; Yakovlev, D. R.; Bayer, M.

    2015-11-01

    We report on spin orientation and alignment of Mn2 + ions in (Cd,Mn)Te diluted magnetic semiconductor crystals using resonant intracenter excitation with circular- and linear-polarized light. The resulting polarized emission of the magnetic ions is observed at low temperatures when the spin relaxation time of the Mn2 + ions is in the order of 1 ms , which considerably exceeds the photoluminescence decay time of 23 μ s . We demonstrate that the experimental data on optical orientation and alignment of Mn2 + ions can be explained using a phenomenological model that is based on the approximation of isolated centers.

  7. Spontaneous perpendicular exchange bias effect in L10-MnGa/FeMn bilayers grown by molecular-beam epitaxy

    NASA Astrophysics Data System (ADS)

    Zhao, X. P.; Lu, J.; Mao, S. W.; Yu, Z. F.; Wei, D. H.; Zhao, J. H.

    2018-01-01

    We report on the spontaneous perpendicular exchange bias effect in as-grown L10-MnGa/FeMn bilayers. An FeMn layer with different thicknesses is introduced as an antiferromagnetic layer to couple with single-crystalline ferromagnetic L10-MnGa, which is epitaxially grown on a GaAs (001) substrate by molecular-beam epitaxy. The perpendicular exchange bias shows a strong dependence on both the thickness of the FeMn layer and the measurement temperature. A large spontaneous perpendicular exchange bias up to 8.9 kOe is achieved in L10-MnGa/FeMn bilayers at 5 K without any external magnetic treatment. The corresponding effective interfacial exchange energy Jeff is estimated to be 1.4 mJ/m2. The spontaneous perpendicular exchange bias effect in the (001) textured L10-MnGa/FeMn bilayers paves the way for spintronic devices based on exchange biased perpendicularly magnetized materials.

  8. DNA methylation at stress-related genes is associated with exposure to early life institutionalization

    PubMed Central

    Non, Amy L.; Hollister, Brittany M.; Humphreys, Kathryn L.; Childebayeva, Ainash; Esteves, Kyle; Zeanah, Charles H.; Fox, Nathan A.; Nelson, Charles A.; Drury, Stacy S.

    2017-01-01

    Objectives Differences in DNA methylation have been associated with early life adversity, suggesting that alterations in methylation function as one pathway through which adverse early environments are biologically embedded. This study examined associations between exposure to institutional care, quantified as the percent time in institutional care at specified follow-up assessment ages, and DNA methylation status in two stress-related genes: FKBP5 and SLC6A4. Materials and Methods We analyzed data from the Bucharest Early Intervention Project, which is a prospective study in which children reared in institutional settings were randomly assigned (mean age 22 months) to either newly created foster care or care as usual (to remain in their current placement) and prospectively followed. A group of children from the same geographic area, with no history of institutionalized caregiving, were also recruited. DNA methylation status was determined in DNA extracted from buccal epithelial cells of children at age 12. Results An inverse association was identified such that more time spent in institutional care was associated with lower DNA methylation at specific CpG sites within both genes. Discussion These results suggest a lasting impact of early severe social deprivation on methylation patterns in these genes, and contribute to a growing literature linking early adversity and epigenetic variation in children. PMID:27218411

  9. Influence of interstitial Mn on magnetism in the room-temperature ferromagnet Mn 1 + δ Sb

    DOE PAGES

    Taylor, Alice E.; Berlijn, Tom; Hahn, Steven E.; ...

    2015-06-15

    We repormore » t elastic and inelastic neutron scattering measurements of the high-TC ferromagnet Mn 1 + δ Sb . Measurements were performed on a large, T C = 434 K, single crystal with interstitial Mn content of δ ≈ 0.13. The neutron diffraction results reveal that the interstitial Mn has a magnetic moment, and that it is aligned antiparallel to the main Mn moment. We perform density functional theory calculations including the interstitial Mn, and find the interstitial to be magnetic in agreement with the diffraction data. The inelastic neutron scattering measurements reveal two features in the magnetic dynamics: i) a spin-wave-like dispersion emanating from ferromagnetic Bragg positions (H K 2n), and ii) a broad, non-dispersive signal centered at forbidden Bragg positions (H K 2n+1). The inelastic spectrum cannot be modeled by simple linear spin-wave theory calculations, and appears to be significantly altered by the presence of the interstitial Mn ions. Finally, the results show that the influence of the interstitial Mn on the magnetic state in this system is more important than previously understood.« less

  10. Home cage locomotor changes in non-human primates after prolonged welding-fume exposure.

    PubMed

    Kim, Choong Yong; Sung, Jae Hyuck; Chung, Yong Hyun; Park, Jung Duck; Han, Jeong Hee; Lee, Jong Seong; Heo, Jeong Doo; Yu, Il Je

    2013-12-01

    To define the relationship between the brain concentration of manganese and neurological signs, such as locomotion, after prolonged welding-fume exposure, cynomolgus monkeys were acclimated for 1 month and then divided into three concentration groups: unexposed, low concentration (31 mg/m(3) total suspended particulate (TSP), 0.9 mg/m(3) of Mn), and high concentration (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of TSP. The monkeys were exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day over 8 months in an inhalation chamber system equipped with an automatic fume generator. The home cage locomotor activity and patterns were determined using a camera system over 2-4 consecutive days. After 25 and 32 weeks of exposure, the home cage locomotor activity of the high-concentration primates was found to be 5-6 times higher than that of the unexposed primates, and this increased locomotor activity was maintained for 7 weeks after ceasing the welding-fume exposure, eventually subsiding to three times higher after 13 weeks of recovery. Therefore, the present results, along with our previous observations of a high magnetic resonance imaging (MRI) T1 signal in the globus pallidus and increased blood Mn concentration, indicate that prolonged welding-fume exposure can cause neurobehavioral changes in cynomolgus monkeys.

  11. Microbial exposure early in life regulates airway inflammation in mice after infection with Streptococcus pneumoniae with enhancement of local resistance.

    PubMed

    Yasuda, Yasuki; Matsumura, Yoko; Kasahara, Kazuki; Ouji, Noriko; Sugiura, Shigeki; Mikasa, Keiichi; Kita, Eiji

    2010-01-01

    The immunological explanation for the "hygiene hypothesis" has been proposed to be induction of T helper 1 (Th1) responses by microbial products. However, the protective results of hygiene hypothesis-linked microbial exposures are currently shown to be unlikely to result from a Th1-skewed response. Until now, effect of microbial exposure early in life on airway innate resistance remained unclear. We examined the role of early life exposure to microbes in airway innate resistance to a respiratory pathogen. Specific pathogen-free weanling mice were nasally exposed to the mixture of microbial extracts or PBS (control) every other day for 28 days and intratracheally infected with Streptococcus pneumoniae 10 days after the last exposure. Exposure to microbial extracts facilitated colonization of aerobic gram-positive bacteria, anaerobic microorganisms, and Lactobacillus in the airway, compared with control exposure. In pneumococcal pneumonia, the exposure prolonged mouse survival days by suppressing bacterial growth and by retarding pneumococcal blood invasion, despite significantly low levels of leukocyte recruitment in the lung. Enhancement of airway resistance was associated with a significant decrease in production of leukocyte chemokine (KC) and TNFalpha, and suppression of matrix metalloproteinase (MMP-9) expression/activation with enhancement of tissue inhibitor of MMP (TIMP-3) activation. The exposure increased production of IFN-gamma, IL-4, and monocyte chemoattractant-1 following infection. Furthermore, expression of Toll-like receptor 2, 4, and 9 was promoted by the exposure but no longer upregulated upon pneumococcal infection. Thus, we suggest that hygiene hypothesis is more important in regulating the PMN-dominant inflammatory response than in inducing a Th1-dominant response.

  12. Early-life exposure to air pollutants and adverse pregnancy outcomes: protocol for a prospective cohort study in Beijing

    PubMed Central

    Song, Jing; Wei, Ling; Ma, Ying; Tian, Ning; Huang, Shi Yun; Dai, Yin Mei; Zhao, Li Hong; Kong, Yuan Yuan

    2017-01-01

    Introduction The association between early exposure to ambient air pollution and adverse pregnancy outcomes in China is unclear. This study will assess the risk of early-life exposure to air pollutants in Beijing and explore the viability of 8-hydroxydeoxyguanosine (8-OHdG) as a biological indicator to assess oxidative stress induced by early-life exposure to air pollution. Methods and analysis Here, 2500 women with singleton pregnancies and their infants will be recruited from the Beijing Obstetrics and Gynecology Hospital. We will collect nine types of biological samples, including maternal serum, urine, placental tissue, umbilical cord tissue and umbilical cord blood during all three trimesters. The air pollution data (particulate matter (PM)2.5, PM10 and similar factors) will be recorded at official fixed-site monitoring stations closest to where the pregnant women live. We plan to assess the effect of air pollutants on adverse pregnancy outcomes and infant respiratory and circulatory disease using Cox regression and competitive risk analysis and explore possible critical windows of exposure during pregnancy using daily pollutant concentrations averaged over various periods of pregnancy combined with individual activity and physiological parameters. Maternal and umbilical cord blood samples (1000 samples) will be randomly selected for 8-OHdG assays to assess the correlation between exposures to air pollutants and oxidative stress. We will determine whether air pollutant exposure or 8-OHdG levels are associated with adverse pregnancy outcomes. SPSS and SAS statistical software will be used for data analysis. Cox regression and competing risk analysis will be used to compute the HR and population attributable risk. Ethics and dissemination This research protocol has already been approved by the Medical Ethics Committee of Beijing Obstetrics and Gynecology Hospital. Written informed consent will be obtained from all study participants prior to enrolment. The

  13. Early-life exposure to air pollutants and adverse pregnancy outcomes: protocol for a prospective cohort study in Beijing.

    PubMed

    Song, Jing; Chen, Yi; Wei, Ling; Ma, Ying; Tian, Ning; Huang, Shi Yun; Dai, Yin Mei; Zhao, Li Hong; Kong, Yuan Yuan

    2017-09-03

    The association between early exposure to ambient air pollution and adverse pregnancy outcomes in China is unclear. This study will assess the risk of early-life exposure to air pollutants in Beijing and explore the viability of 8-hydroxydeoxyguanosine (8-OHdG) as a biological indicator to assess oxidative stress induced by early-life exposure to air pollution. Here , 2500 women with singleton pregnancies and their infants will be recruited from the Beijing Obstetrics and Gynecology Hospital. We will collect nine types of biological samples, including maternal serum, urine, placental tissue, umbilical cord tissue and umbilical cord blood during all three trimesters. The air pollution data (particulate matter (PM)2.5, PM10 and similar factors) will be recorded at official fixed-site monitoring stations closest to where the pregnant women live. We plan to assess the effect of air pollutants on adverse pregnancy outcomes and infant respiratory and circulatory disease using Cox regression and competitive risk analysis and explore possible critical windows of exposure during pregnancy using daily pollutant concentrations averaged over various periods of pregnancy combined with individual activity and physiological parameters. Maternal and umbilical cord blood samples (1000 samples) will be randomly selected for 8-OHdG assays to assess the correlation between exposures to air pollutants and oxidative stress. We will determine whether air pollutant exposure or 8-OHdG levels are associated with adverse pregnancy outcomes. SPSS and SAS statistical software will be used for data analysis. Cox regression and competing risk analysis will be used to compute the HR and population attributable risk. This research protocol has already been approved by the Medical Ethics Committee of Beijing Obstetrics and Gynecology Hospital. Written informed consent will be obtained from all study participants prior to enrolment. The results will be published in peer-reviewed journals or

  14. Impacts of triclosan exposure on zebrafish early-life stage: Toxicity and acclimation mechanisms.

    PubMed

    Falisse, Elodie; Voisin, Anne-Sophie; Silvestre, Frédéric

    2017-08-01

    Triclosan (TCS) is a broad spectrum antibacterial agent widely used in personal care products and present in most aquatic ecosystems. This study investigated the occurrence of triclosan acclimation and the biological mechanisms underlying the stress response triggered in early-life stage of zebrafish. Zebrafish eggs were first exposed to four different sublethal concentrations of TCS (2, 20, 50 and 100μg/L) for 7days following fertilization and subsequently exposed to a lethal concentration of TCS (1000μg/L). During the time-to-death exposure (TTD), mortality was continuously recorded to evaluate if increased resistance occurred. Overall, larvae exposed to 50μg/L of TCS demonstrated higher sensitivity, with delayed hatching and increased mortality during the sub-lethal exposure and significant lower mean time-to-death (TTD) value compared to the other groups. Interestingly, fish exposed to the highest concentration of TCS (100μg/L) presented a similar mean TTD value as controls and a significantly better survival in comparison with embryos exposed to 50μg/L, suggesting that acclimation process has been triggered at this concentration. Proteomic and enzymatic analyses were conducted on 7days post fertilization (dpf) larvae exposed to 50μg/L and 100μg/L of TCS giving insights into the functional changes triggered at those specific concentrations. TCS seemed to affect proteins involved in cytoskeleton, stress response, eyes and neuronal development. This was endorsed by the enzymatic results, which suggest impairment in glutathione metabolism and acute neurotoxicity. A significant 2.5-fold and 3-fold increase of AChE activity was observed following TCS exposure. Moreover, GPx activity was significantly increased whereas a significant inhibition of GR activity was observed, suggesting that de novo synthesis of reduced GSH might occur in order to maintain the ratio between reduced and oxidized GSH. Proteomic results revealed possible candidate protein involved in

  15. Early Adolescent Boys' Exposure to Internet Pornography: Relationships to Pubertal Timing, Sensation Seeking, and Academic Performance

    ERIC Educational Resources Information Center

    Beyens, Ine; Vandenbosch, Laura; Eggermont, Steven

    2015-01-01

    Research has demonstrated that adolescents regularly use Internet pornography. This two-wave panel study aimed to test an integrative model in early adolescent boys (M[subscript age] = 14.10; N = 325) that (a) explains their exposure to Internet pornography by looking at relationships with pubertal timing and sensation seeking, and (b) explores…

  16. Comparison of stationary and personal air sampling with an air dispersion model for children’s ambient exposure to manganese

    EPA Science Inventory

    Manganese (Mn) is ubiquitous in the environment and essential for normal growth and development, yet excessive exposure can lead to impairments in neurological function. This study modeled ambient Mn concentrations as an alternative to stationary and personal air sampling to asse...

  17. Structural Diversities in Heterometallic Mn-Ca Cluster Chemistry from the Use of Salicylhydroxamic Acid: {MnIII4Ca2}, {MnII/III6Ca2}, {MnIII/IV8Ca}, and {MnIII8Ca2} Complexes with Relevance to Both High- and Low-Valent States of the Oxygen-Evolving Complex.

    PubMed

    Alaimo, Alysha A; Koumousi, Evangelia S; Cunha-Silva, Luís; McCormick, Laura J; Teat, Simon J; Psycharis, Vassilis; Raptopoulou, Catherine P; Mukherjee, Shreya; Li, Chaoran; Gupta, Sayak Das; Escuer, Albert; Christou, George; Stamatatos, Theocharis C

    2017-09-05

    One-pot reactions between the [Mn 3 O(O 2 CPh) 6 (py) x ] +/0 triangular precursors and either CaBr 2 ·xH 2 O or CaCl 2 ·6H 2 O, in the presence of salicylhydroxamic acid (shaH 2 ), have afforded the heterometallic complexes [Mn III 4 Ca 2 (O 2 CPh) 4 (shi) 4 (H 2 O) 3 (Me 2 CO)] (1) and (pyH)[Mn II 2 Mn III 4 Ca 2 Cl 2 (O 2 CPh) 7 (shi) 4 (py) 4 ] (2), respectively, in good yields. Further reactions but using a more flexible synthetic scheme comprising the Mn(NO 3 ) 2 ·4H 2 O/Ca(NO 3 ) 2 ·4H 2 O and Mn(O 2 CPh) 2 ·2H 2 O/Ca(ClO 4 ) 2 ·4H 2 O "metal blends" and shaH 2 , in the presence of external base NEt 3 , led to the new complexes (NHEt 3 ) 2 [Mn III 4 Mn IV 4 Ca(OEt) 2 (shi) 10 (EtOH) 2 ] (3) and (NHEt 3 ) 4 [Mn III 8 Ca 2 (CO 3 ) 4 (shi) 8 ] (4), respectively. In all reported compounds, the anion of the tetradentate (N,O,O,O)-chelating/bridging ligand salicylhydroxime (shi 3- ), resulting from the in situ metal-ion-assisted amide-iminol tautomerism of shaH 2 , was found to bridge both Mn and Ca atoms. Complexes 1-4 exhibit a variety of different structures, metal stoichiometries, and Mn oxidation-state descriptions; 1 possesses an overall octahedral metal arrangement, 2 can be described as a Mn 4 Ca 2 octahedron bound to an additional Mn 2 unit, 3 consists of a Mn 8 "ring" surrounding a Ca II atom, and 4 adopts a rectangular cuboidal motif of eight Mn atoms accommodating two Ca II atoms. Solid-state direct-current magnetic susceptibility studies revealed the presence of predominant antiferromagnetic exchange interactions between the Mn centers, leading to S = 0 spin ground-state values for all complexes. From a bioinorganic chemistry perspective, the reported compounds may demonstrate some relevance to both high-valent scheme (3) and lower-oxidation-level species (1, 2, and 4) of the catalytic cycle of the oxygen-evolving complex.

  18. The impact of high-salt exposure on cardiovascular development in the early chick embryo.

    PubMed

    Wang, Guang; Zhang, Nuan; Wei, Yi-Fan; Jin, Yi-Mei; Zhang, Shi-Yao; Cheng, Xin; Ma, Zheng-Lai; Zhao, Shu-Zhu; Chen, You-Peng; Chuai, Manli; Hocher, Berthold; Yang, Xuesong

    2015-11-01

    In this study, we show that high-salt exposure dramatically increases chick mortality during embryo development. As embryonic mortality at early stages mainly results from defects in cardiovascular development, we focused on heart formation and angiogenesis. We found that high-salt exposure enhanced the risk of abnormal heart tube looping and blood congestion in the heart chamber. In the presence of high salt, both ventricular cell proliferation and apoptosis increased. The high osmolarity induced by high salt in the ventricular cardiomyocytes resulted in incomplete differentiation, which might be due to reduced expression of Nkx2.5 and GATA4. Blood vessel density and diameter were suppressed by exposure to high salt in both the yolk sac membrane (YSM) and chorioallantoic membrane models. In addition, high-salt-induced suppression of angiogenesis occurred even at the vasculogenesis stage, as blood island formation was also inhibited by high-salt exposure. At the same time, cell proliferation was repressed and cell apoptosis was enhanced by high-salt exposure in YSM tissue. Moreover, the reduction in expression of HIF2 and FGF2 genes might cause high-salt-suppressed angiogenesis. Interestingly, we show that high-salt exposure causes excess generation of reactive oxygen species (ROS) in the heart and YSM tissues, which could be partially rescued through the addition of antioxidants. In total, our study suggests that excess generation of ROS might play an important role in high-salt-induced defects in heart and angiogenesis. © 2015. Published by The Company of Biologists Ltd.

  19. Importance of trivalency and the eg1 configuration in the photocatalytic oxidation of water by Mn and Co oxides

    PubMed Central

    Maitra, Urmimala; Naidu, B. S.; Govindaraj, A.; Rao, C. N. R.

    2013-01-01

    Prompted by the early results on the catalytic activity of LiMn2O4 and related oxides in the photochemical oxidation of water, our detailed study of several manganese oxides has shown that trivalency of Mn is an important factor in determining the catalytic activity. Thus, Mn2O3, LaMnO3, and MgMn2O4 are found to be very good catalysts with turnover frequencies of 5 × 10−4 s−1, 4.8 × 10−4 s−1, and 0.8 ×10−4 s−1, respectively. Among the cobalt oxides, Li2Co2O4 and LaCoO3—especially the latter—exhibit excellent catalytic activity, with the turnover frequencies being 9 × 10−4 s−1 and 1.4 × 10−3 s−1, respectively. The common feature among the catalytic Mn and Co oxides is not only that Mn and Co are in the trivalent state, but Co3+ in the Co oxides is in the intermediate t2g5eg1 state whereas Mn3+ is in the t2g3eg1 state. The presence of the eg1 electron in these Mn and Co oxides is considered to play a crucial role in the photocatalytic properties of the oxides. PMID:23818589

  20. Effects of chronic crude oil exposure on early developmental stages of the Northern krill (Meganyctiphanes norvegica).

    PubMed

    Arnberg, Maj; Moodley, Leon; Dunaevskaya, Evgenia; Ramanand, Sreerekha; Ingvarsdóttir, Anna; Nilsen, Marianne; Ravagnan, Elisa; Westerlund, Stig; Sanni, Steinar; Tarling, Geraint A; Bechmann, Renée K

    2017-01-01

    Rising oil and gas activities in northern high latitudes have led to an increased risk of petroleum pollution in these ecosystems. Further, seasonal high UV radiation at high latitudes may elevate photo-enhanced toxicity of petroleum pollution to marine organisms. Zooplanktons are a key ecological component of northern ecosystems; therefore, it is important to assess their sensitivity to potential pollutants of oil and gas activity. As ontogenetic development may be particularly sensitive, the aim of this study was to examine the impact of chronic exposure to oil water dispersion (OWD) on development and feeding of early life stages of the Northern krill, Meganyctiphanes norvegica. In a range of experiments, embryonic, nonfeeding, and feeding larval stages were exposed to concentrations of between 0.01 and 0.1 mg/L of oil or photo-modified oil for 19 and 21 d. No significant effects on egg respiration, hatching success, development, length and larval survival were observed from these treatments. Similarly, evolution of fatty acid composition patterns during ontogenetic development was unaffected. The results indicates a high degree of resilience of these early developmental stages to such types and concentrations of pollutants. However, feeding and motility in later calyptopis-stage larvae were significantly impaired at exposure of 0.1 mg/L oil. Data indicate that feeding larval stage of krill was more sensitive to OWD than early nonfeeding life stages. This might be attributed to the narcotic effects of oil pollutants, their direct ingestion, or accumulated adverse effects over early development.

  1. Early Antibiotic Exposure in Low-resource Settings Is Associated With Increased Weight in the First Two Years of Life

    PubMed Central

    Rogawski, Elizabeth T.; Platts-Mills, James A.; Seidman, Jessica C.; John, Sushil; Mahfuz, Mustafa; Ulak, Manjeswori; Shrestha, Sanjaya; Soofi, Sajid B.; Yori, Pablo Penataro; Mduma, Estomih; Svensen, Erling; Ahmed, Tahmeed; Lima, Aldo A.M.; Bhutta, Zulfiqar; Kosek, Margaret; Lang, Dennis; Gottlieb, Michael; Zaidi, Anita; Kang, Gagandeep; Bessong, Pascal; Houpt, Eric R.; Guerrant, Richard L.

    2017-01-01

    ABSTRACT Objectives: The potential growth-promoting effects of antibiotics are not well understood among undernourished children in environments with high pathogen exposure. We aimed to assess whether early antibiotic exposure duration and class were associated with growth to 2 years of age across 8 low-resource sites in the MAL-ED birth cohort study. Methods: We followed 1954 children twice per week from birth to 2 years to record maternally reported antibiotic exposures and measure anthropometry monthly. We estimated the associations between antibiotic exposure before 6 months of age and weight-for-age and length-for-age (LAZ) z scores to 2 years. We assessed the impact of class-specific exposures and duration, and compared these results to effects of antibiotic exposures after 6 months of age. Results: Antibiotic use before 6 months of age was associated with increased weight from 6 months to 2 years, whereas associations with length were less consistent across sites and antibiotic classes. Compared to unexposed children, 2 or more courses of metronidazole, macrolides, and cephalosporins were associated with adjusted increases in weight-for-age of 0.24 (95% confidence interval (CI): 0.04, 0.43), 0.23 (95% CI: 0.05, 0.42), and 0.19 (95% CI: 0.04, 0.35) from 6 months to 2 years, respectively. Conclusions: Antibiotic use in low-resource settings was most associated with the ponderal growth of children who had multiple exposures to antibiotics with broad spectrum and anaerobic activity in early infancy. Opportunities for rational and targeted antibiotic therapy in low resource settings may also promote short-term weight gain in children, although longer-term physical growth and metabolic impacts are unknown. PMID:28604514

  2. Magnetic and conventional shape memory behavior of Mn-Ni-Sn and Mn-Ni-Sn(Fe) alloys

    NASA Astrophysics Data System (ADS)

    Turabi, A. S.; Lázpita, P.; Sasmaz, M.; Karaca, H. E.; Chernenko, V. A.

    2016-05-01

    Magnetic and conventional shape memory properties of Mn49Ni42Sn9(at.%) and Mn49Ni39Sn9Fe3(at.%) polycrystalline alloys exhibiting martensitic transformation from ferromagnetic austenite into weakly magnetic martensite are characterized under compressive stress and magnetic field. Magnetization difference between transforming phases drastically increases, while transformation temperature decreases with the addition of Fe. Both Mn49Ni42Sn9 and Mn49Ni39Sn9Fe3 alloys show remarkable superelastic and shape memory properties with recoverable strain of 4% and 3.5% under compression at room temperature, respectively. These characteristics can be counted as extraordinary among the polycrystalline NiMn-based magnetic shape memory alloys. Critical stress for phase transformation was increased by 34 MPa in Mn49Ni39Sn9Fe3 and 21 MPa in Mn49Ni42Sn9 at 9 T, which can be qualitatively understood in terms of thermodynamic Clausius-Clapeyron relationships and in the framework of the suggested physical concept of a volume magnetostress.

  3. Thermodynamic data from redox reactions at high temperatures. II. The MnO-0Mn3O4 oxygen buffer, and implications for the thermodynamic properties of MnO and Mn3O4

    NASA Astrophysics Data System (ADS)

    O'Neill, Hugh St. C.; Pownceby, Mark I.

    1993-09-01

    Theμ _{O_2 } defined by the reaction 6 MnO+O2 =2 Mn3O4 has been determined from 917 to 1,433 K using electrochemical cells (with calcia-stabilized zirconta, CSZ) of the type: MediaObjects/410_2005_BF01046534_f2.tif Steady emfs were achieved rapidly at all temperatures on both increasing and decreasing temperature, indicating that the MnO-Mn3O4 oxygen buffer equilibrates relatively easily. It therefore makes a useful alternative choice in experimental petrology to Fe2O3-Fe3O4 for buffering oxygen potentials at oxidized values. The results are (in J/mol, temperature in K, reference pressure 1 bar);μ _{O_2 } (±200)=-563,241+1,761.758 T-220.490 T in T+0.101819 T 2 with an uncertainty of ±200 J/mol. Third law analysis of these data, including a correction for the deviations in stoichiometry of MnO, implies S 298.15 for Mn3O4 of 166.6 J/K · mol, which is 2.5 J/K · mol higher than the calorimetric determination of Robie and Hemingway (1985). The low value of the calorimetric entropy may be due to incomplete ordering of the magnetic spins. The third law value of Δ r H {298.15/0} is-450.09 kJ/mol, which is significantly different from the calorimetric value of-457.5±3.4 kJ/mol, calculated from Δ f H {298.15/0} of MnO and Mn3O4, implying a small error in one or both of these latter.

  4. Expanding the Hygiene Hypothesis: Early Exposure to Infectious Agents Predicts Delayed-Type Hypersensitivity to Candida among Children in Kilimanjaro

    PubMed Central

    Wander, Katherine; O'Connor, Kathleen; Shell-Duncan, Bettina

    2012-01-01

    Background Multiple lines of evidence suggest that infections in early life prevent the development of pathological immune responses to allergens and autoantigens (the hygiene hypothesis). Early infections may also affect later immune responses to pathogen antigen. Methods To evaluate an association between early infections and immune responses to pathogen antigen, delayed-type hypersensitivity (DTH) to Candida albicans was evaluated among 283 2- to 7-year-old children in Kilimanjaro, Tanzania. A questionnaire and physical examination were used to characterize variables reflecting early exposure to infectious agents (family size, house construction materials, BCG vaccination, hospitalization history). Logistic regression was used to evaluate the association between early exposure to infectious agents and DTH to C. albicans. Results Triceps skinfold thickness (OR: 1.11; 95% CI: 1.01, 1.22) and age (OR: 1.27; 95% CI: 1.04, 1.55) were positively associated with DTH to C. albicans. Adjusted for age and sex, large family size (OR: 2.81; 95% CI: 1.04, 7.61), BCG vaccination scar (OR: 3.10; 95% CI: 1.10, 8.71), and hospitalization during infancy with an infectious disease (OR: 4.67; 95% CI: 1.00, 21.74) were positively associated with DTH to C. albicans. Conclusions Early life infections were positively associated with later DTH to C. albicans. This result supports an expansion of the hygiene hypothesis to explain not only pathological immune responses to allergens, but also appropriate immune responses to pathogens. Immune system development may be responsive to early infections as an adaptive means to tailor reactivity to the local infectious disease ecology. PMID:22616000

  5. Early life exposure to bisphenol A investigated in mouse models of airway allergy, food allergy and oral tolerance.

    PubMed

    Nygaard, Unni Cecilie; Vinje, Nina Eriksen; Samuelsen, Mari; Andreassen, Monica; Groeng, Else-Carin; Bølling, Anette Kocbach; Becher, Rune; Lovik, Martinus; Bodin, Johanna

    2015-09-01

    The impact of early life exposure to bisphenol A (BPA) through drinking water was investigated in mouse models of respiratory allergy, food allergy and oral tolerance. Balb/c mice were exposed to BPA (0, 10 or 100 μg/ml), and the offspring were intranasally exposed to the allergen ovalbumin (OVA). C3H/HeJ offspring were sensitized with the food allergen lupin by intragastric gavage, after exposure to BPA (0, 1, 10 or 100 μg/ml). In separate offspring, oral tolerance was induced by gavage of 5 mg lupin one week before entering the protocol for the food allergy induction. In the airway allergy model, BPA (100 μg/ml) caused increased eosinophil numbers in bronchoalveolar lavage fluid (BALF) and a trend of increased OVA-specific IgE levels. In the food allergy and tolerance models, BPA did not alter the clinical anaphylaxis or antibody responses, but induced alterations in splenocyte cytokines and decreased mouse mast cell protease (MMCP)-1 serum levels. In conclusion, early life exposure to BPA through drinking water modestly augmented allergic responses in a mouse model of airway allergy only at high doses, and not in mouse models for food allergy and tolerance. Thus, our data do not support that BPA promotes allergy development at exposure levels relevant for humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Magnetotransport study of Dirac fermions in YbMnBi2 and CaMnBi2

    NASA Astrophysics Data System (ADS)

    Wang, Aifeng; Zaliznyak, Igor; Graf, David; Ren, Weijun; Wang, Kefeng; Wu, Lijun; Garlea, Ovidiu; Warren, John; Bozin, Emil; Zhu, Yimei; Petrovic, Cedomir

    It is well known that AMnBi2 (A = alkaline earth) with two dimensional (2D) bismuth layer host quasi-2D Dirac states similar to graphene and topological insulators. The Dirac state is significantly affected by the alkaline earth in the block layer. Angle-resolved photoemission spectroscopy (ARPES) indicates that YbMnBi2 could be the first Weyl semimetal with time-reversal symmetry breaking, whereas the anisotropic Dirac state in SrMnBi2 can host a valley-polarized interlayer current through magnetic valley control. Here, we study in-plane magnetotransport in YbMnBi2, and interlayer magnetotransport in CaMnBi2. The angular-dependent magnetoresistance, nonzero Berry phase, and small cyclotron mass confirm the presence of Dirac fermion and quasi-2D fermi surface in YbMnBi2. The interlayer electronic transport in CaMnBi2 suggest valley polarized conduction and a Dirac state on the side wall of the warped cylindrical Fermi surface of CaMnBi2. Work at BNL was supported by the U.S. Department of Energy-BES, Division of Materials Science and Engineering, under Contract No. DE-SC0012704. Work at the National High Magnetic Field Laboratory is supported by the NSF Cooperative Agreement No. DMR-06541.

  7. Stability of Li- and Mn-Rich Layered-Oxide Cathodes within the First-Charge Voltage Plateau

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Iddir, Hakim; Bareño, Javier; Benedek, Roy

    Li and Mn rich layered oxides xLi 2MnO 3•(1-x)LiMO 2 enable high capacity and energy density Li-ion batteries, but undergo structural transformations during the first charge that degrade their performance, and result in Voltage Fade upon cycling. First-principles density-functional-theory simulations reveal atomic transformations that occur in the bulk during the first charge. The simulations and experiment (particularly XRD) show that the O and Mn sublattices remain intact during the early part of the voltage plateau, and significant transformations occur only well into the voltage plateau, with perhaps close to half of the Li in the Li 2MnO 3 domains removed.more » That Voltage Fade is actually observed experimentally for a first charge with only minimal activation (extending only slightly beyond the onset of the voltage plateau) may be a consequence of surface and interface instabilities. Implications for the achievement of high energy-density, low-fade battery operation are discussed.« less

  8. Early chronic low-level lead exposure produces glomerular hypertrophy in young C57BL/6J mice☆

    PubMed Central

    Basgen, John M.; Sobin, Christina

    2014-01-01

    Early chronic lead exposure continues to pose serious health risks for children, particularly those living in lower socioeconomic environments. This study examined effects on developing glomeruli in young C57BL/6J mice exposed to low (30 ppm), higher (330 ppm) or no lead via dams’ drinking water from birth to sacrifice on post-natal day 28. Low-level lead exposed mice [BLL mean (SD); 3.19 (0.70) μg/dL] had an increase in glomerular volume but no change in podocyte number compared to control mice [0.03 (0.01) μg/dL]. Higher-level lead exposed mice [14.68 (2.74) μg/dL] had no change in either glomerular volume or podocyte number. The increase in glomerular volume was explained by increases in glomerular capillary and mesangial volumes with no change in podocyte volume. Early chronic lead exposure yielding very low blood lead levels alters glomerular development in pre-adolescent animals. PMID:24300173

  9. Early Alcohol Exposure Disrupts Visual Cortex Plasticity in Mice

    PubMed Central

    Lantz, Crystal L.; Wang, Weili; Medina, Alexandre E.

    2012-01-01

    There is growing evidence that deficits in neuronal plasticity underlie the cognitive problems seen in fetal alcohol spectrum disorders (FASD). However, the mechanisms behind these deficits are not clear. Here we test the effects of early alcohol exposure on ocular dominance plasticity (ODP) in mice and the reversibility of these effects by phosphodiesterase (PDE) inhibitors. Mouse pups were exposed to 5 g/kg of 25% ethanol i.p. on postnatal days (P) 5, 7 and 9. This type of alcohol exposure mimics binge drinking during the third trimester equivalent of human gestation. To assess ocular dominance plasticity animals were monocularly deprived at P21 for 10 days, and tested using optical imaging of intrinsic signals. During the period of monocular deprivation animals were treated with vinpocetine (20mg/kg; PDE1 inhibitor), rolipram (1.25 mg/Kg; PDE4 inhibitor), vardenafil (3 mg/Kg; PDE5 inhibitor) or vehicle solution. Monocular deprivation resulted in the expected shift in ocular dominance of the binocular zone in saline controls but not in the ethanol group. While vinpocetine successfully restored ODP in the ethanol group, rolipram and vardenafil did not. However, when rolipram and vardenafil were given simultaneously ODP was restored. PDE4 and PDE5 are specific to cAMP and cGMP respectively, while PDE1 acts on both of these nucleotides. Our findings suggest that the combined activation of the cAMP and cGMP cascades may be a good approach to improve neuronal plasticity in FASD models. PMID:22617459

  10. The contributions of early adverse experiences and trajectories of respiratory sinus arrhythmia on the development of neurobehavioral disinhibition among children with prenatal substance exposure

    PubMed Central

    Conradt, Elisabeth; Degarmo, David; Fisher, Phil; Abar, Beau; Lester, Barry M.; Lagasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Hammond, Jane A.

    2015-01-01

    Neurobehavioral disinhibition (ND) is a complex condition reflecting a wide range of problems involving difficulties with emotion regulation and behavior control. Respiratory sinus arrhythmia (RSA) is a physiological correlate of emotion regulation that has been studied in a variety of at-risk populations; however, there are no studies of RSA in children with ND. Data were drawn from a prospective longitudinal study of prenatal substance exposure that included 1,073 participants. Baseline RSA and RSA reactivity to an attention-demanding task were assessed at 3, 4, 5, and 6 years. ND was assessed at ages 8/9, 11, and 13/14 years via behavioral dysregulation and executive dysfunction composite measures. Greater exposure to early adversity was related to less RSA reactivity at 3 years, increases in RSA reactivity from ages 3 to 6 years, and increased behavioral dysregulation from ages 8/9 to 13/14. RSA reactivity was examined as a moderator of the association between early adversity and changes in ND. A significant Early Adversity × RSA Reactivity quadratic interaction revealed that children with decelerations in RSA reactivity exhibited increases in behavioral dysregulation, regardless of their exposure to early adversity. However, greater exposure to early adversity was related to greater increases in behavioral dysregulation, but only if children exhibited accelerations in RSA reactivity from ages 3 to 6 years. The results contribute to our understanding of how interactions across multiple levels of analysis contribute to the development of ND. PMID:24909973

  11. The Effect of Early Life Antibiotic Exposures on Diarrheal Rates Among Young Children in Vellore, India

    PubMed Central

    Westreich, Daniel; Becker-Dreps, Sylvia; Adair, Linda S.; Sandler, Robert S.; Sarkar, Rajiv; Kattula, Deepthi; Ward, Honorine D.; Meshnick, Steven R.; Kang, Gagandeep

    2015-01-01

    Background: Antibiotic treatment of childhood illnesses is common in India. In addition to contributing to antimicrobial resistance, antibiotics might result in increased susceptibility to diarrhea through interactions with the gastrointestinal microbiota. Breast milk, which enriches the microbiota early in life, may increase the resilience of the microbiota against perturbations by antibiotics. Methods: In a prospective observational cohort study, we assessed whether antibiotic exposures from birth to 6 months affected rates of diarrhea up to age 3 years among 465 children from Vellore, India. Adjusting for treatment indicators, we modeled diarrheal rates among children exposed and unexposed to antibiotics using negative binomial regression. We further assessed whether the effect of antibiotics on diarrheal rates was modified by exclusive breastfeeding at 6 months. Results: More than half of the children (n = 267, 57.4%) were given at least one course of antibiotics in the first 6 months of life. The adjusted relative incidence rate of diarrhea was 33% higher among children who received antibiotics under 6 months of age compared with those who did not (incidence rate ratio: 1.33, 95% confidence interval: 1.12, 1.57). Children who were exclusively breastfed until 6 months of age did not have increased diarrheal rates following antibiotic use. Conclusions: Antibiotic exposures early in life were associated with increased rates of diarrhea in early childhood. Exclusive breastfeeding might protect against this negative impact. PMID:25742244

  12. Magneto-optical studies of ensembles of semimagnetic self-organized Cd(Mn)Se/Zn(Mn)Se Quantum Dots

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Reshina, I. I.; Ivanov, S. V.; Toropov, A. A.

    2013-12-04

    Ensembles of Cd(Mn)Se/ZnSe and CdSe/Zn(Mn)Se semimagnetic self-organized quantum dots with different Mn content have been studied by photoluminescence and resonant Raman scattering under strong magnetic fields in Faraday and Voigt geometries and with spectral and polarization selective excitation. Electron spin-flip Raman scattering has been observed in Voigt geometry in the structures with large Mn content. Narrow exciton peaks completely σ{sup −}σ{sup +} polarized have been observed under selective excitation in Faraday geometry in the structures with medium and small Mn content. A number of specific effects manifested themselves in the structures with a smallest Mn content where no Zeeman shiftmore » of the photoluminescence bands was observed.« less

  13. Biomonitoring and biomarkers of organophosphate pesticides exposure - state of the art.

    PubMed

    Kapka-Skrzypczak, Lucyna; Cyranka, Małgorzata; Skrzypczak, Maciej; Kruszewski, Marcin

    2011-01-01

    Human biomonitoring provides an efficient and cost-effective way to identify and quantify exposure to chemical substances, including those having deleterious eff ects on human organisms. Once the risk of hazardous exposure has been identified and the mechanism of toxic eff ects has been elucidated, an ultimate decision about how to reduce exposure can be made. A particularly high risk of exposure to hazardous chemicals is associated with the use of pesticides in agriculture, especially the use of organophosphorous pesticides (OP), which are the most widely and commonly used insecticides worldwide. There is some strong evidence that chronic exposure to these compounds may have adverse eff ects on health. Exposure to pesticides has been associated with an increase in the incidence of non-Hodgkin's lymphoma, multiple myeloma, soft tissue sarcoma, lung sarcoma, and cancer of the pancreas, stomach, liver, bladder and gall bladder, Parkinson disease, Alzheimer disease, and reproductive outcomes. In view of these findings, the detection of populations at risk constitutes a very important topic. The biomonitoring studies on individuals exposed to pesticides have shown an elevated level of indicators of DNA damage, such as chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), and recently, single cell gel electrophoresis (SCGE). The cytogenetic markers of DNA damage have become very popular and useful in providing an analytical data for risk assessment, such as internal exposure doses and early biological eff ects of both occupational and environmental exposure to pesticides. The article describes the usefulness and the limitations of these biomarkers in biomonitoring studies of populations exposed to pesticides, with regard to the main routes of uptake and different matrices, which can be used to monitor risk assessment in occupational settings. The article also summarizes the latest reports about biomarkers of susceptibility, and mentions other

  14. Early work-related physical exposures and low back pain in midlife: the Cardiovascular Risk in Young Finns Study.

    PubMed

    Lallukka, T; Viikari-Juntura, E; Viikari, J; Kähönen, M; Lehtimäki, T; Raitakari, O T; Solovieva, S

    2017-03-01

    To examine whether heavy physical workload in young adulthood increases the risk of local and radiating low back pain (LBP) in midlife. Longitudinal nationally representative Young Finns Study data among women (n=414) and men (n=324), aged 18-24 years in 1986 (baseline), were used. Physical heaviness of work was reported at baseline and follow-up (2007), and local and radiating LBP at follow-up. Covariates were age, smoking and body mass index. Logistic regression was used to examine the associations between physical heaviness of work and LBP. Additionally, the mediating effect of back pain at baseline was examined (the Sobel test). After adjustment for the covariates, and as compared with sedentary/light physical workload, heavy physical workload was associated with radiating LBP among women (OR 4.09, 95% CI 1.62 to 10.31) and men (OR 2.01, 95% CI 1.06 to 3.82). Among men, early back pain mediated the association (p value from the Sobel test=0.006). Among women, early exposure to physically heavy work showed the most consistent associations, while early and late exposures were associated with radiating and local LBP among men. Persistently heavy physical work was associated with radiating LBP among women and men. Physically heavy work at a young age can have a long-lasting effect on the risk of LBP, radiating LBP in particular. These results highlight the need to consider early and persistent exposures to prevent the adverse consequences of physical workload for the low back. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Exposure to Movie Reckless Driving in Early Adolescence Predicts Reckless, but Not Inattentive Driving.

    PubMed

    Kostermans, Evelien; Stoolmiller, Mike; de Leeuw, Rebecca N H; Engels, Rutger C M E; Sargent, James D

    2014-01-01

    We examine the association between exposure to depictions of reckless driving in movies and unsafe driving, modeling inattentive and reckless driving as separate outcomes. Data were obtained by telephone from 1,630 US adolescents aged 10 to 14 years at baseline who were drivers at a survey 6 years later. Exposure to movie reckless driving was measured based on movies seen from a randomly selected list of 50 movie titles that had been content coded for reckless driving among characters. Associations were tested with inattentive and reckless driving behaviors in the subsequent survey-controlling for baseline age, sex, socioeconomic status, parental education, school performance, extracurricular activities, daily television and video/computer game exposure, number of movies watched per week, self-regulation and sensation seeking. Exposure to movie reckless driving was common, with approximately 10% of movie characters having driven recklessly. Confirmatory factor analysis revealed a significant distinction between items tapping reckless and inattentive driving at the 6th wave. Age and exposure to movie reckless driving at baseline were directly associated with wave-6 reckless (but not inattentive) driving. Additionally, growth in sensation seeking mediated a prospective relation between the total number of movies watched per week at baseline and reckless driving, independent of exposure to movie reckless driving. Males and high sensation seekers reported lower seatbelt usage and more reckless driving, whereas lower self-regulation predicted inattentive driving. In this study, exposure to movie reckless driving during early adolescence predicted adolescents' reckless driving, suggesting a direct modeling effect. Other aspects of movies were also associated with reckless driving, with that association mediated through growth in sensation seeking. Predictors of reckless driving were different from predictors of inattentive driving, with lower self-regulation associated

  16. Exposure to Movie Reckless Driving in Early Adolescence Predicts Reckless, but Not Inattentive Driving

    PubMed Central

    Kostermans, Evelien; Stoolmiller, Mike; de Leeuw, Rebecca N. H.; Engels, Rutger C. M. E.; Sargent, James D.

    2014-01-01

    Objective We examine the association between exposure to depictions of reckless driving in movies and unsafe driving, modeling inattentive and reckless driving as separate outcomes. Methods Data were obtained by telephone from 1,630 US adolescents aged 10 to 14 years at baseline who were drivers at a survey 6 years later. Exposure to movie reckless driving was measured based on movies seen from a randomly selected list of 50 movie titles that had been content coded for reckless driving among characters. Associations were tested with inattentive and reckless driving behaviors in the subsequent survey–controlling for baseline age, sex, socioeconomic status, parental education, school performance, extracurricular activities, daily television and video/computer game exposure, number of movies watched per week, self-regulation and sensation seeking. Results Exposure to movie reckless driving was common, with approximately 10% of movie characters having driven recklessly. Confirmatory factor analysis revealed a significant distinction between items tapping reckless and inattentive driving at the 6th wave. Age and exposure to movie reckless driving at baseline were directly associated with wave-6 reckless (but not inattentive) driving. Additionally, growth in sensation seeking mediated a prospective relation between the total number of movies watched per week at baseline and reckless driving, independent of exposure to movie reckless driving. Males and high sensation seekers reported lower seatbelt usage and more reckless driving, whereas lower self-regulation predicted inattentive driving. Discussion In this study, exposure to movie reckless driving during early adolescence predicted adolescents’ reckless driving, suggesting a direct modeling effect. Other aspects of movies were also associated with reckless driving, with that association mediated through growth in sensation seeking. Predictors of reckless driving were different from predictors of inattentive driving

  17. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis.

    PubMed

    Esaiassen, Eirin; Fjalstad, Jon Widding; Juvet, Lene Kristine; van den Anker, John N; Klingenberg, Claus

    2017-07-01

    To systematically review and meta-analyse the relationship between antibiotic exposure in neonates and the following early adverse outcomes: necrotizing enterocolitis (NEC), invasive fungal infections (IFIs) and/or death. Data sources were PubMed, Embase, Medline and the Cochrane Database (to December 2016), supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic exposures (yes versus no, long versus short duration, and/or broad- versus narrow-spectrum regimens) and the risk of developing NEC, IFI and/or death in the neonatal period. Two reviewers extracted data and evaluated the risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, meta-analyses were conducted using the random-effect model. We identified 9 RCTs and 38 observational studies. The quality of the majority of studies was poor to moderate. There was a significant association between prolonged antibiotic exposure and an increased risk of NEC in five observational studies (5003 participants) and/or risk of death in five observational studies (13 534 participants). Eleven of 15 studies with data on broad- versus narrow-spectrum regimens reported an increased risk of IFI after broad-spectrum antibiotic exposure, in particular with third-generation cephalosporins and carbapenems. Meta-analysis was limited by few and old RCTs, insufficient sample sizes and diversity of antibiotic exposure and outcomes reported. Prolonged antibiotic exposure in uninfected preterm infants is associated with an increased risk of NEC and/or death, and broad-spectrum antibiotic exposure is associated with an increased risk of IFI. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Family Interactions, Exposure to Violence, and Emotion Regulation: Perceptions of Children and Early Adolescents at Risk

    ERIC Educational Resources Information Center

    Houltberg, Benjamin J.; Henry, Carolyn S.; Morris, Amanda Sheffield

    2012-01-01

    This study examined the protective nature of youth reports of family interactions in relation to perceived exposure to violence and anger regulation in 84 children and early adolescents (mean age of 10.5; 7-15 years old) primarily from ethnic minority groups and living in high-risk communities in a large southwestern city. Path analysis and…

  19. Movement disorder symptoms associated with Unified Parkinson’s Disease Rating Scale (UPDRS) in two manganese (Mn)-exposed communities

    EPA Science Inventory

    Objectives: The UPDRS is a commonly used neurological measurement to assess the presence and severity of parkinsonian symptoms. It has also been used to assess symptoms associated with Mn exposure. Objectives: to determine 1) if movement disorder symptoms were associated with UP...

  20. Early ethanol exposure and vinpocetine treatment alter learning- and memory-related proteins in the rat hippocampus and prefrontal cortex.

    PubMed

    Swart, Patricia C; Currin, Christopher B; Russell, Vivienne A; Dimatelis, Jacqueline J

    2017-05-01

    This study investigates the effects of early exposure to ethanol on cognitive function and neural plasticity-related proteins in the rat brain. Sprague-Dawley rats were administered 12% ethanol solution (4 g/kg/day i.p.) or saline from P4 to P9. Vinpocetine, a phosphodiesterase type 1 inhibitor, was tested to determine whether it could reverse any changes induced by early ethanol exposure. Hence, from P25 to P31, ethanol-exposed male rats were injected with vinpocetine (20 mg/kg/day i.p.) or vehicle (DMSO) prior to undergoing behavioral testing in the open field and Morris water maze (MWM) tests. Ethanol exposure did not adversely affect spatial memory in the MWM. A key finding in this study was a significant ethanol-induced change in the function of the phosphorylated extracellular signal-related kinase (P-ERK) signaling pathway in the prefrontal cortex (PFC) and dorsal hippocampus (DH) of rats that did not display overt behavioral deficits. The P-ERK/ERK ratio was decreased in the PFC and increased in the DH of ethanol-exposed rats compared with controls. Rats that received vinpocetine in addition to ethanol did not display any behavioral changes but did show alterations in neural plasticity-related proteins. Mitogen-activated protein kinase phosphatase was increased, whereas brain-derived neurotrophic factor was decreased, in the PFC of vinpocetine-treated ethanol-exposed rats, and phosphorylated-glycogen synthase kinase β and synaptophysin were increased in the DH of these rats. This study provides insight into the long-term effects of early ethanol exposure and its interaction with vinpocetine in the rat brain. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.