Erin N. Haynes

Altered myelination and axonal integrity in adults with childhood lead exposure: A diffusion tensor imaging study

Childhood lead exposure is associated with adverse cognitive, neurobehavioral and motor outcomes, suggesting altered brain structure and function. The purpose of this work was to assess the long-term impact of childhood lead exposure on white matter integrity in young adults. We hypothesized that childhood lead exposure would alter adult white matter architecture via deficits in axonal integrity and myelin organization. Adults (22.9+/-1.5 years, range 20.0-26.1 years) from the Cincinnati Lead Study were recruited to undergo a study employing diffusion tensor imaging (DTI). The anatomic regions of association between water diffusion characteristics in white matter and mean childhood blood lead level were determined for 91 participants (52 female). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on an exploratory voxel-wise basis. In adjusted analyses, mean childhood blood lead levels were associated with decreased FA throughout white matter. Regions of the corona radiata demonstrated highly significant lead-associated decreases in FA and AD and increases in MD and RD. The genu, body, and splenium of the corpus callosum demonstrated highly significant lead-associated decreases in RD, smaller and less significant decreases in MD, and small areas with increases in AD. The results of this analysis suggest multiple insults appear as distinct patterns of white matter diffusion abnormalities in the adult brain. Neurotoxic insults from the significant lead burden the participants experienced throughout childhood affect neural elements differently and may be related to the developmental stage of myelination at periods of exposure. This study indicates that childhood lead exposure is associated with a significant and persistent impact on white matter microstructure as quantified with diffusivity changes suggestive of altered myelination and axonal integrity.

ENVIRONMENTAL MANGANESE EXPOSURE IN RESIDENTS LIVING NEAR A FERROMANGANESE REFINERY IN SOUTHEAST OHIO: A PILOT STUDY

Manganese (Mn) is an essential element, yet is neurotoxic in excess. The majority of Mn research has been conducted on occupationally exposed adults with few studies focused on an environmentally exposed population. Marietta, OH is home to one of the largest airborne Mn emission sources in the United States, a ferromanganese refinery. In preparation for a community-based participatory research study, a preliminary pilot study was initiated to characterize the communitys exposure to Mn in ambient air and to evaluate the relationship between biological indices of Mn exposure and genes associated with Mn metabolism in Marietta area residents. Participants in the pilot study were recruited through newspaper advertisement, fliers and direct mailing. Exposure to ambient Mn was estimated using an air pollution dispersion model, AERMOD. A total of 141 residents participated in the pilot study ranging in age from 2 to 81 years. Estimated annual average ambient air Mn concentrations in the study area obtained from AERMOD varied from 0.02 to 2.61 microg/m(3). Mean blood and hair Mn values were 9.12 microg/L (SD 3.90) and 5.80 microg/g (SD 6.40 microg/g), respectively and were significantly correlated (r=0.30, p<0.01). Blood and hair Mn was significantly associated within families (r=0.27, p=<0.02 and r=0.43, p<0.01), respectively. The relationship between hair Mn and estimated ambient air Mn became significant when genes for iron metabolism were included in linear models. The preliminary ambient air and biological concentrations of Mn found in this population demonstrate the need for further research into potential health effects.

Manganese Exposure and Neurocognitive Outcomes in Rural School-Age Children: The Communities Actively Researching Exposure Study (Ohio, USA)

Background Manganese (Mn) plays a vital role in brain growth and development, yet excessive exposure can result in neurotoxicity. Marietta, Ohio, is home to the nation’s longest-operating ferromanganese refinery, and community concern about exposure led to the development of the research study. Objectives Our overall goal was to address the community’s primary research question: “Does Mn affect cognitive development of children?” We evaluated the relationships between Mn exposure as measured by blood and hair Mn, along with other neurotoxicants including blood lead (Pb) and serum cotinine, and child cognition. Methods Children 7–9 years of age were enrolled (n = 404) in the Communities Actively Researching Exposure Study (CARES) from Marietta and Cambridge, Ohio, and their surrounding communities from October 2008 through March 2013. Blood and hair were analyzed for Mn and Pb, and serum was analyzed for cotinine. We used penalized splines to assess potential nonlinear associations between biological measures and IQ subscale scores, followed by multivariable regression models with categorical variables based on quartiles of the distribution for biological measures with nonlinear associations and continuous variables for biological measures with linear associations. Results Geometric mean blood (n = 327) and hair Mn (n = 370) concentrations were 9.67 ± 1.27 μg/L and 416.51 ± 2.44 ng/g, respectively. After adjusting for potential confounders, both low and high blood and hair Mn concentrations were associated with lower Full Scale IQ and subscale scores, with significant negative associations between the highest quartile and middle two quartiles of blood Mn (β –3.51; 95% CI: –6.64, –0.38) and hair Mn (β –3.66; 95% CI: –6.9, –0.43%) and Full Scale IQ. Conclusions Both low and high Mn concentrations in blood and hair were negatively associated with child IQ scores. Serum cotinine was negatively associated with child cognitive function. Citation Haynes EN, Sucharew H, Kuhnell P, Alden J, Barnas M, Wright RO, Parsons PJ, Aldous KM, Praamsma ML, Beidler C, Dietrich KN. 2015. Manganese exposure and neurocognitive outcomes in rural school-age children: the Communities Actively Researching Exposure Study (Ohio, USA). Environ Health Perspect 123:1066–1071; http://dx.doi.org/10.1289/ehp.1408993

Exposure of Firefighters to Particulates and Polycyclic Aromatic Hydrocarbons

Firefighting continues to be among the most hazardous yet least studied occupations in terms of exposures and their relationship to occupational disease. Exposures are complex, involving mixtures of particles and chemicals such as polycyclic aromatic hydrocarbons (PAHs). Adverse health effects associated with these agents include elevated incidences of coronary heart disease and several cancers. PAHs have been detected at fire scenes, and in the firehouse rest area and kitchen, routinely adjoining the truck bay, and where firefighters spend a major part of each shift. An academic-community partnership was developed with the Cincinnati Fire Department with the goal of understanding active firefighters’ airborne and dermal PAH exposure. PAHs were measured in air and particulates, and number and mass concentrations, respectively, of submicron (0.02–1 μm) and PM2.5 (2.5 μm diameter and less) particles during overhaul events in two firehouses and a University of Cincinnati administrative facility as a comparison location. During overhaul firefighters evaluate partially combusted materials for re-ignition after fire extinguishment and commonly remove Self-Contained Breathing Apparatus (SCBA). Face and neck wipes were also collected at a domestic fire scene. Overhaul air samples had higher mean concentrations of PM2.5 and submicron particles than those collected in the firehouse, principally in the truck bay and kitchen. Among the 17 PAHs analyzed, only naphthalene and acenaphthylene were generally detectable. Naphthalene was present in 7 out of 8 overhaul activities, in 2 out of 3 firehouse (kitchen and truck bay) samples, and in none collected from the control site. In firefighter face and neck wipes a greater number of PAHs were found, several of which have carcinogenic activity, such as benzofluoranthene, an agent also found in overhaul air samples. Although the concentration for naphthalene, and all other individual PAHs, was very low, the potential simultaneous exposure to multiple chemicals even in small quantities in combination with high ultrafine particle exposure deserves further study. It is recommended that personal respiratory and skin protection be worn throughout the overhaul process.

Effect of chronic low level manganese exposure on postural balance: a pilot study of residents in southern Ohio.

Objective:The objective of this study was to determine the effect of non-occupational exposure to manganese (Mn) on postural balance. Methods:Residents living near a ferromanganese refinery provided hair and blood samples after postural balance testing. The relationship between hair Mn and postural balance was analyzed with logistic regression. Following covariate adjustment, postural balance was compared with control data by analysis of covariance. Results:Mean hair Mn was 4.4 &mgr;g/g. A significantly positive association was found between hair Mn and sway area (eyes open on the platform, P = 0.05; eyes closed on the platform, P = 0.04) and sway length (eyes open on the platform, P = 0.05; eyes closed on the platform, P = 0.04). Postural balance of residents was significantly larger than controls in 5 out of 8 postural balance outcomes. Conclusion:Preliminary findings suggest subclinical impairment in postural balance among residents chronically exposed to ambient Mn. A prospective study with a larger sample size is warranted.

Assessment of personal exposure to manganese in children living near a ferromanganese refinery.

Airborne exposure to manganese (Mn) can result in neurologic effects. Stationary air sampling is the traditional technique to assess Mn exposure for communities, yet may not accurately reflect childrens personal exposure. The goal of the study was to characterize personal exposure to Mn and PM(2.5) in a cohort of children ages 7-9 years residing near a ferromanganese refinery. A subset of children living in non-smoking households ages 7-9 enrolled in the Marietta Community Actively Researching Exposure Study during March-June 2009 and 2010 were invited to participate. Blood and hair were collected and analyzed for Mn. Participants wore a PM(2.5) sampler (Personal Modular Impactor) for 48 h. TWD was based on time spent at home and school and the distance of each from the refinery. Stationary outdoor air sampling was conducted 8 km from the refinery using a Harvard-type PM(2.5) impactor. The relationship between personal Mn exposure and TWD was examined by multiple regression adjusting for stationary air Mn concentration, wind speed and direction, and precipitation. Complete personal air sampling data were collected on 38 children. TWD ranged from 4.7 km to 28.5 km with a mean distance of 11.1 (4.7 sd) km. Mn concentration in personal air samples ranged from 1.5 ng/m3 to 54.5 ng/m3 (geometric mean, 8.1 ng/m3). TWD was a significant predictor of natural log personal air Mn concentration (lnMn) with an associated decrease of 0.075 lnMn for each km TWD (p<0.05, 95% CI -0.13 to -0.01). Personal Mn exposures were positively associated with stationary air Mn levels and inversely associated with wind speed. A childs location (home and school) relative to the refinery is a significant predictor of personal Mn exposure. Wind speed is also an important contributor to personal Mn exposure.

Air pollution and stillbirth risk: exposure to airborne particulate matter during pregnancy is associated with fetal death.

Objective To test the hypothesis that exposure to fine particulate air pollution (PM2.5) is associated with stillbirth. Study Design Geo-spatial population-based cohort study using Ohio birth records (2006-2010) and local measures of PM2.5, recorded by the EPA (2005-2010) via 57 monitoring stations across Ohio. Geographic coordinates of the mother’s residence for each birth were linked to the nearest PM2.5 monitoring station and monthly exposure averages calculated. The association between stillbirth and increased PM2.5 levels was estimated, with adjustment for maternal age, race, education level, quantity of prenatal care, smoking, and season of conception. Results There were 349,188 live births and 1,848 stillbirths of non-anomalous singletons (20-42 weeks) with residence ≤10 km of a monitor station in Ohio during the study period. The mean PM2.5 level in Ohio was 13.3 μg/m3 [±1.8 SD, IQR(Q1: 12.1, Q3: 14.4, IQR: 2.3)], higher than the current EPA standard of 12 μg/m3. High average PM2.5 exposure through pregnancy was not associated with a significant increase in stillbirth risk, adjOR 1.21(95% CI 0.96,1.53), nor was it increased with high exposure in the 1st or 2nd trimester. However, exposure to high levels of PM2.5 in the third trimester of pregnancy was associated with 42% increased stillbirth risk, adjOR 1.42(1.06,1.91). Conclusions Exposure to high levels of fine particulate air pollution in the third trimester of pregnancy is associated with increased stillbirth risk. Although the risk increase associated with high PM2.5 levels is modest, the potential impact on overall stillbirth rates could be robust as all pregnant women are potentially at risk.

Developing a bidirectional academic-community partnership with an Appalachian-American community for environmental health research and risk communication.

Background: Marietta, Ohio, is an Appalachian-American community whose residents have long struggled with understanding their exposure to airborne manganese (Mn). Although community engagement in research is strongly endorsed by the National Institutes of Health and the National Institute of Environmental Health Sciences in particular, little has been documented demonstrating how an academic–community partnership that implements the community-based participatory research (CBPR) principles can be created and mobilized for research. Objectives: We created a bidirectional, academic–community partnership with an Appalachian-American community to a) identify the community’s thoughts and perceptions about local air quality, its effect on health, and the perception of risk communication sources and b) jointly develop and conduct environmental health research. Methods: We formed a community advisory board (CAB), jointly conducted pilot research studies, and used the results to develop a community-driven research agenda. Results: Persons in the community were “very concerned” to “concerned” about local air quality (91%) and perceived the air quality to have a direct impact on their health and on their children’s health (93% and 94%, respectively). The CAB identified the primary research question: “Does Mn affect the cognition and behavior of children?” Although the community members perceived research scientists as the most trusted and knowledgeable regarding risks from industrial emissions, they received very little risk information from research scientists. Conclusions: Engaging a community in environmental health research from its onset enhanced the quality and relevance of the research investigation. The CBPR principles were a useful framework in building a strong academic–community partnership. Because of the current disconnect between communities and research scientists, academic researchers should consider working collaboratively with community-based risk communication sources.

Clinical and Translational Scientist Career Success: Metrics for Evaluation

Despite the increased emphasis on formal training in clinical and translational research and the growth in the number and scope of training programs over the past decade, the impact of training on research productivity and career success has yet to be fully evaluated at the institutional level. In this article, the Education Evaluation Working Group of the Clinical and Translational Science Award Consortium introduces selected metrics and methods associated with the assessment of key factors that affect research career success. The goals in providing this information are to encourage more consistent data collection across training sites, to foster more rigorous and systematic exploration of factors associated with career success, and to help address previously identified difficulties in program evaluation. Clin Trans Sci 2012; Volume 5: 400–407

Childhood exposure to manganese and postural instability in children living near a ferromanganese refinery in southeastern Ohio

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, and 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.