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Inhalation of welding fumes can cause metal accumulation in the brain, leading to Parkinsonian-like symptoms. Metal accumulation and altered neurochemical profiles have been observed using magnetic resonance imaging (MRI) in highly exposed welders, being associated with decreased motor function and cognition. While MRI is impractical to use as a health risk assessment tool in occupational settings, toenail metal levels are easier to assess and have been demonstrated to reflect an exposure window of 7-12 months in the past. Yet, it is unclear whether toenail metal levels are associated with brain metal levels or changes in metabolism, which are the root of potential health concerns. This study investigates whether toenail manganese (Mn) and iron (Fe) levels, assessed at several time points, correlate with brain Mn and Fe levels, measured by MRI, as well as brain GABA, glutamate (Glu), and glutathione (GSH) levels, measured by Magnetic Resonance Spectroscopy (MRS), in seventeen Mn-exposed welders. Quantitative T1 and R2* MRI maps of the whole brain, along with GABA, Glu, and GSH MRS measurements from the thalamus and cerebellum were acquired at baseline (T0). Toenail clippings were collected at T0 and every three months after the MRI for a year to account for different exposure periods being reflected by toenail clippings and MRI. Spearman correlations of toenail metal levels were run against brain metal and metabolite levels, but no significant associations were found for Mn at any timepoint. Cerebellar GSH positively correlated with toenail Fe clipped twelve months after the MRI (p = 0.05), suggesting an association with Fe exposure at the time of the MRI. Neither thalamic GABA nor Glu correlated with toenail Fe levels. In conclusion, this study cannot support toenail Mn as a proxy for brain Mn levels or metabolic changes, while toenail Fe appears linked to brain metabolic alterations, underscoring the importance of considering other metals, including Fe, in studying Mn neurotoxicity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ulrike Dydak reports a relationship with American Regent Inc that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fire agencies across the United States must make complex resource allocation decisions to manage wildfires using a national network of shared firefighting resources. Firefighters play a critical role in suppressing fires and protecting vulnerable communities. However, they are exposed to health and safety risks associated with fire, smoke inhalation, and infectious disease transmission. The COVID-19 pandemic further complicated these risks, prompting fire agencies to propose resource management adaptations to minimize COVID-19 exposure and transmission. It is unclear if and how the pandemic may have operationally influenced wildland firefighting personnel resource use given compounding wildfire and COVID-19 risks. Therefore, we developed generalized linear mixed models that were fit using multiple integrated datasets to detect changes in personnel resource use for years prior to and during the COVID-19 pandemic, while controlling for historical fire and landscape conditions, societal risks, and management objectives. Analyses of observed and predicted firefighting resource use revealed reductions in the mean personnel resources used per wildfire per day during the pandemic for models developed across the western U.S. and for various western U.S. fire regions. Notably, the Northern California and the Great Basin Coordination Centers showed statistically significant reductions in ground personnel use during the COVID-19 pandemic. Learning from wildland fire management strategies and resource use trends that occurred during the COVID-19 pandemic, fire agencies can better anticipate resource constraints that may arise during the compounding threats of severe wildland fire activity and infectious disease outbreaks to proactively prepare and adapt suppression management strategies., (© 2024. The Author(s).)

Arsenic (As) and lead (Pb) are environmental pollutants found in common sites linked to similar adverse health effects. This study determined driving factors of neurotoxicity on the developing cerebral vasculature with As and Pb mixture exposures. Cerebral vascular toxicity was evaluated at mixture concentrations of As and Pb representing human exposures levels (10 or 100 parts per billion; ppb; µg/L) in developing zebrafish by assessing behavior, morphology, and gene expression. In the visual motor response assay, hyperactivity was observed in all three outcomes in dark phases in larvae with exposure (1-120 h post fertilization, hpf) to 10 ppb As, 10 ppb Pb, or 10 ppb mix treatment. Time spent moving exhibited hyperactivity in dark phases for 100 ppb As and 100 ppb mix treatment groups only. A decreased brain length and ratio of brain length to total length in the 10 ppb mix group was measured with no alterations in other treatment groups or other endpoints (i.e., total larval length, head length, or head width). Alternatively, measurements of cerebral vasculature in the midbrain and cerebellum uncovered decreased total vascularization at 72 hpf in all treatment groups in the mesencephalon and in all treatment groups, except the 100 ppb Pb and 10 ppb As groups, in the cerebellum. In addition, decreased sprouting and branching occurred in the mesencephalon, while only decreased branching was measured in the cerebellum. The 10 ppb Pb group showed several cerebral vasculature modifications that were aligned with a specific gene expression alteration pattern different from other treatment groups. Additionally, the 100 ppb As group drove gene alterations, along with several other endpoints, for changes observed in the 100 ppb mix treatment group. Perturbations assessed in this study displayed non-linear concentration-responses, which are important to consider in environmental health outcomes for As and Pb neurotoxicity.

Background and Purpose: Children with developmental disabilities have increased risk of epilepsy and need for overnight video electroencephalographic (EEG) monitoring. However, video EEGs have historically been considered difficult to complete for this population. An autism support service at a pediatric tertiary care hospital implemented a coordinated team approach to help children with developmental disability tolerate overnight video EEGs. The project included completion of a caregiver-report preprocedure questionnaire that then was shared with the multidisciplinary team and used to create individualized care plans. The current study aims to describe rates of video EEG completion and need for lead placement under general anesthesia among children with autism and related disabilities who received these supports. Methods: Rates of video EEG completion and general anesthesia use were analyzed for children referred to the support service between April 2019 and November 2021. Results: A total of 182 children with developmental disability (mean age   = 10.3 years, 54.9% diagnosed with autism) met inclusion criteria. 92.9% (n   = 169) of children successfully completed EEG (leads on ≥12 hours). Only 19.2% (n   = 35) required general anesthesia for video EEG lead placement. The majority (80.2%) of parents (n   = 146) completed the preprocedure questionnaire. Video EEG outcomes did not differ based on completion of the questionnaire. Parent-reported challenges with communication and cooperation were associated with shorter video EEG duration and greater use of general anesthesia. Conclusions: These findings suggest that most children with developmental disability can complete video EEG with sufficient support. Preprocedure planning can identify children who would benefit from additional accommodations. Further research is necessary to clarify which supports are most helpful., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Although manganese (Mn) is a trace metal essential for humans, chronic exposure to Mn can cause accumulation of this metal ion in the brain leading to an increased risk of neurological and neurobehavioral health effects. This is a concern for welders exposed to Mn through welding fumes. While brain Mn accumulation in occupational settings has mostly been reported in the basal ganglia, several imaging studies also revealed elevated Mn in other brain areas. Since Mn functions as a magnetic resonance imaging (MRI) T1 contrast agent, we developed a whole-brain MRI approach to map in vivo Mn deposition differences in the brains of non-exposed factory controls and exposed welders. This is a cross-sectional analysis of 23 non-exposed factory controls and 36 exposed full-time welders from the same truck manufacturer. We collected high-resolution 3D MRIs of brain anatomy and R1 relaxation maps to identify regional differences using voxel-based quantification (VBQ) and statistical parametric mapping. Furthermore, we investigated the associations between excess Mn deposition and neuropsychological and motor test performance. Our results indicate that: (1) Using whole-brain MRI relaxometry methods we can generate excess Mn deposition maps in vivo, (2) excess Mn accumulation due to occupational exposure occurs beyond the basal ganglia in cortical areas associated with motor and cognitive functions, (3) Mn likely diffuses along white matter tracts in the brain, and (4) Mn deposition in specific brain regions is associated with exposure (cerebellum and frontal cortex) and motor metrics (cerebellum and hippocampus)., Competing Interests: Declaration of competing interest UD reports recent consulting with American Regent, Inc. The other authors do not have any financial conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: We describe 5 children with GFAP astrocytopathy with the goal of further characterizing this rare form of meningoencephalomyelitis. Methods: Retrospective chart review of patients diagnosed with GFAP astrocytopathy between 2019 and 2021. Results: Patients were 8-17 years old, and all were male. Fever, headache, and vomiting were common presenting symptoms, and weakness, tremor, and ataxia were common initial examination findings. Initial magnetic resonance imaging (MRI) showed spinal cord abnormalities in 2 patients and leptomeningeal enhancement in 1. Most patients had cerebral spinal fluid pleocytosis, and all screened negative for malignancy. Three patients progressed to coma, and all were treated with immunosuppressant therapy. By discharge, all patients had improved over their clinical nadir, although none had returned to baseline. Discussion: GFAP astrocytopathy is a recently recognized cause of meningoencephalomyelitis in children. Here, we expand our understanding of this entity with the goal of aiding those treating children with GFAP astrocytopathy., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In the last 20 years, the field of biotechnology has made significant progress and attracted substantial investments, leading to different paths of technological modernization among nations. As a result, there is now an international divide in the commercial and intellectual capabilities of biotechnology, and the implications of this divergence are not well understood. This raises important questions about why global actors are motivated to participate in biotechnology modernization, the challenges they face in achieving their goals, and the possible future direction of global biotechnology development. Using the framework of prospect theory, this paper explores the role of risk culture as a fundamental factor contributing to this divergence. It aims to assess the risks and benefits associated with the early adoption of biotechnology and the regulatory frameworks that shape the development and acceptance of biotechnological innovations. By doing so, it provides valuable insights into the future of biotechnology development and its potential impact on the global landscape., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Trump, Cummings, Loschin, Keisler, Wells and Linkov.)

Background and Objective: Bone strontium (Sr) is a reliable biomarker for studying related bone health outcomes and the effectiveness of Sr supplements in osteoporosis disease treatment. In this study, we evaluated the sensitivity of portable x-ray fluorescence (XRF) technology for in vivo bone Sr quantification among adults., Materials and Methods: Sr-doped bone-equivalent phantoms were used for system calibration. Using the portable XRF, we measured bone Sr levels in vivo in mid-tibia bone in 76 adults, 38-95 years of age, living in Indiana, US; we also analyzed bone data of 29 adults, 53-82 years of age, living in Shanghai, China. The same portable XRF device and system settings were used in measuring their mid-tibia bone. We compared bone Sr concentrations by sex, age, and recruitment site. We also used multiple linear regression model to estimate the association of age with bone Sr concentration, adjusting for sex and recruitment site., Results: The uncertainty of in vivo individual measurement increased with higher soft tissue thickness overlying bone, and it ranged from 1.0 ug/g dry bone (ppm) to 2.4 ppm with thickness ranging from 2 to 7 mm, with a measurement time of 5 min. Geometric mean (95% confidence interval (CI)) of the bone Sr concentration was 79.1 (70.1, 89.3) ppm. After adjustment for recruitment site and sex, an increase in five years of age was associated with a 8.9% (95% CI: 2.5%, 15.6%) increase in geometric mean bone Sr concentration., Discussion and Conclusion: Sr concentrations were consistently well above detection limits of the portable XRF, and exhibited an expected increase with age. These data suggest that the portable XRF can be a valuable technology to quantify Sr concentration in bone, and in the study of Sr-related health outcomes among adults, such as bone mineral density (BMD) and bone fracture risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Many studies evaluating methylmercury (MeHg) toxicity rely on whole blood total mercury (THg) measurements to estimate MeHg exposure. However, whole blood THg includes other forms of mercury (Hg), such as inorganic Hg, which have different exposure sources and toxicological effects than MeHg. Therefore, estimating the whole blood MeHg/THg ratio is critical to predicting MeHg exposure and, subsequently, efforts to establish an exposure-response relationship for use in risk assessment. A large, representative dataset (National Health and Nutrition Examination Survey (NHANES) 2011-2016) was used to determine the whole blood MeHg/THg ratio among (a) self-reported fish and shellfish consumers, ≥ 15 years of age (the "full adult" population (N = 5268 training dataset; N = 2336 test dataset)) and (b) female fish and shellfish consumers, 15-44 years of age (the "women of reproductive age" population (N = 1285 training dataset; N = 560 test dataset)). Unadjusted and adjusted linear and spline models with direct measurements for both THg and MeHg were evaluated. The mean whole blood MeHg/THg ratio was 0.75 (95% confidence interval (CI): 0.74, 0.75). This ratio was significantly higher among those with higher THg concentrations. All models exhibited excellent fit (adjusted R 2 from 0.957 to 0.982). Performance was slightly improved in spline versus linear models. For the full adult population and women of reproductive age, the unadjusted spline model predicted whole blood MeHg concentrations of 5.65 µg/L and 5.55 µg/L, respectively, when the THg concentration was 5.80 µg/L. These results suggest that whole blood THg is a good predictor of whole blood MeHg among fish and shellfish consumers., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Determining factors correlated with protective measures against COVID-19 is important to improve public health response. This study describes student opinions related to university COVID-19 preventive measures., Methods: In fall 2020, 643 US university students completed an online survey on perception, awareness, and adherence to COVID-19 preventive measures. Outcomes included protocol effectiveness (self or others), protocol adherence (self or others), consequences of protocol violation, knowledge of violations, and level of concern for COVID-19. Multiple linear regression models determined correlates of outcome variables. Covariates included gender, race, residence, area of study, class, and knowledge of someone with a positive COVID-19 test., Results: Overall, students agreed with protective measures (equivalent to higher scores). In adjusted linear models, females (versus males) had significantly higher scores for protocol effectiveness (self) (p < 0.001), consequences of protocol violation (p = 0.005), and concern about COVID-19 (p < 0.001). Asian/Pacific Islander (versus white) had significantly higher scores for protocol effectiveness (self) (p < 0.001), consequences of protocol violation (p = 0.008), and concern about COVID-19 (p = 0.001). Graduate students (versus freshman) had higher scores for protocol effectiveness (self) (p < 0.001), protocol adherence (self) (p = 0.004) and concern about COVID-19 (p < 0.001). In contrast, participants who had a positive COVID-19 test had significantly lower scores for protocol effectiveness (self) (p = 0.02), protocol adherence (self) (p = 0.004), and consequences of protocol violation (p = 0.008)., Conclusion: Overall, females, Asian/Pacific Islanders, and graduate students were more likely to agree with or adhere to COVID-19 prevention guidelines but those who tested positive for COVID-19 were less likely to do so. These results may inform future prevention efforts., (© 2022. The Author(s).)

This observational study was conducted to determine the prevalence and correlates of wearing masks at a large Midwestern US university during the COVID-19 pandemic. A total of 7,237 individuals were observed over 24 hours. Overall mask use prevalence was 90.6% (95% confidence interval: 89.9, 91.2); mask use was significantly associated with being indoors (vs outdoors), female (vs male), and at the athletic center (vs the student union)., (Copyright © 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Manganese (Mn) is an essential element. However, Mn overexposure is associated with motor dysfunction. This cross-sectional study assessed the association between bone Mn (BnMn) and whole blood Mn (BMn) with motor function in 59 Chinese workers. BnMn and BMn were measured using a transportable in vivo neutron activation analysis system and inductively coupled plasma mass spectrometry, respectively. Motor function (manual coordination, postural sway, postural hand tremor, and fine motor function) was assessed using the Coordination Ability Test System (CATSYS) and the Purdue Pegboard. Relationships between Mn biomarkers and motor test scores were analyzed with linear regression models adjusted for age, education, current employment, and current alcohol consumption. BMn was significantly inversely associated with hand tremor intensity (dominant hand (β=-0.04, 95 % confidence interval (CI):-0.07, -0.01; non-dominant hand β=-0.05, 95 % CI:-0.08, -0.01) hand tremor center frequency (non-dominant hand β=-1.61, 95 % CI:-3.03, -0.19) and positively associated with the Purdue Pegboard Assembly Score (β = 4.58, 95 % CI:1.08, 8.07). BnMn was significantly inversely associated with finger-tapping performance (non-dominant hand β=-0.02, 95 % CI:-0.04,-0.004), mean sway (eyes closed and foam β=-0.68, 95 % CI:-1.31,-0.04), and positively associated with hand tremor center frequency (dominant hand, β = 0.40, 95 % CI:0.002, 0.80). These results suggest BMn is related to better postural hand tremor and fine motor control and BnMn is related to worse motor coordination and postural hand tremor but better (i.e., less) postural sway. The unexpected positive results might be explained by choice of biomarker or confounding by work-related motor activities. Larger, longitudinal studies in this area are recommended., (Copyright © 2021 Elsevier B.V. All rights reserved.)

There have been considerations since the beginning of the Coronavirus pandemic that COVID-19 infection, like any other viral illness, can trigger neurological and metabolic decompensation in patients with mitochondrial diseases. At the time of writing, there were no published reports reviewing experiences and guidelines about management of COVID-19 infection in this patient population. We present a challenging case of an adult patient with a known diagnosis of Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes (MELAS) complicated by COVID-19 infection. She initially presented with altered mental status and vomiting and went on to develop a stroke-like episode, pancreatitis, and pneumatosis intestinalis. We review salient features of her hospitalization, including initiation of thromboprophylaxis in relation to intravenous arginine therapy, caution regarding medications such as remdesivir, and the incidence of gastrointestinal complications., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Historic industrial activity led to extensive lead and arsenic contamination within residential areas of East Chicago, Indiana, United States. Although remediation is underway, community concerns about this contamination remain. Therefore, the goal for this analysis was to characterize environmental contamination in soil within and around these areas. A total of 228 samples from 32 different sites (addresses) were collected by community members or study staff. These were analyzed for metals using portable x-ray fluorescence or inductively coupled plasma ̶ optical emission spectroscopy. Concentrations exceeding EPA screening levels were found for 42% of the soil arsenic samples, 35% of the soil lead samples, and 79% of the soil manganese samples; a few samples also contained elevated copper or zinc. Concentrations above EPA screening levels were identified both within and outside of the formally designated contaminated area. Roughly 30% of all sites had at least one sample above and one sample below the screening level for arsenic, lead, and manganese. For sites within the contaminated area, more than 90% (arsenic), 60% (lead) and 60% (manganese) of the samples exceeded EPA screening levels. There was a significant association of proximity to the historic industrial site with elevated soil concentrations of arsenic and lead; a similar association was present for manganese. These results are consistent with existing data for lead and arsenic and we additionally report elevated concentrations of manganese and a high within-site variability of all metal concentrations. These findings should be considered in future remediation efforts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The coronavirus disease 2019 pandemic has presented an enormous challenge to healthcare providers worldwide. The appropriate use of personal protective equipment (PPE) has been essential to ensure staff and patient safety. The 'PPE Helper Programme' was developed at a large London hospital group to counteract suboptimal PPE practice. Based on a behaviour change model of capability, opportunity and motivation (COM-B), the programme provided PPE support, advice and education to ward staff., Aim: Evaluation of the PPE Helper Programme., Methods: Clinical and non-clinical ward staff completed a questionnaire informed by the Theoretical Domains Framework and COM-B model. The questionnaire was available in paper and electronic versions. Quantitative responses were analysed using descriptive and non-parametric statistics, and free-text responses were analysed thematically., Findings: Over a 6-week period, PPE helpers made 268 ward visits. Overall, 261 questionnaires were available for analysis. Across the Trust, 68% of respondents reported having had contact with a PPE helper. Staff who had encountered a PPE helper responded significantly more positively to a range of statements about using PPE than staff who had not encountered a PPE helper. Black and minority ethnic staff were significantly more anxious regarding the adequacy of PPE. Non-clinical and redeployed staff (e.g. domestic staff) were most positive about the impact of PPE helpers. Free-text comments showed that staff found the PPE Helper Programme supportive and would have liked it earlier in the pandemic., Conclusion: The PPE Helper Programme is a feasible and beneficial intervention for providing support, advice and education to ward staff during infectious disease outbreaks., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Aluminum (Al) is a neurotoxicant; however, efforts to understand Al toxicity are limited by the lack of a quantitative biomarker of cumulative exposure. Bone Al measurements may address this need. Here, we describe and compare non-invasive bone Al measurements with fingernail Al and Al cumulative exposure indices (CEIs)., Methods: We completed a cross-sectional study of 43 factory workers in Zunyi, China. Bone Al measurements were taken with a compact in-vivo neutron activation analysis system (IVNAA). Fingernail samples were analyzed using inductively coupled plasma mass spectrometry. CEIs, based on self-reported work history and prior literature, were calculated for the prior 5, 10, 15, 20 years and lifetime work history. Linear regressions adjusted for age and education compared fingernail Al and Al CEIs with bone Al., Results: Median (interquartile range (IQR)) Al measurements were: 15 μg/g dry bone (IQR = 28) for bone Al; 34.9 μg/g (43.3) for fingernail; and 24 (20) for lifetime CEI. In adjusted regression models, an increase in 15-year CEI was significantly associated with increased bone Al (β = 0.91, 95% confidence interval (CI): 0.16, 1.66). Associations of bone Al with 10- and 20-year CEI were approaching statistical significance (β = 0.98, 95% CI: -0.14, 2.1; β = 0.59, 95% CI: -0.01, 1.18, respectively). Other models were not statistically significant., Conclusions: Bone Al was significantly associated with 15-year Al CEI, but not other Al CEIs or fingernail Al. Bone Al may be a useful measure of cumulative, rather than short-term, Al exposure. Additional refinement of this method is ongoing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Fish/seafood consumption is a source of mercury; other dietary sources are not well described. This cross-sectional study used National Health and Nutrition Examination Survey (NHANES) 2011-2012 data. Participants self-reported consuming fish/seafood (N = 5427) or not (N = 1770) within the past 30 days. Whole blood total mercury (THg), methylmercury (MeHg), and urinary mercury (UHg) were determined. Diet was assessed using 24 h recall. Adjusted regression models predicted mercury biomarker concentrations with recent food consumption, while controlling for age, sex, education, and race/ethnicity. Geometric mean THg was 0.89 µg/L (95% confidence interval (CI): 0.78, 1.02) (seafood consumers) and 0.31 µg/L (95% CI: 0.28, 0.34) (non-seafood consumers); MeHg and UHg concentrations follow similar patterns. In adjusted regressions among seafood consumers, significant associations were observed between mercury biomarkers with multiple foods, including fish/seafood, wine, rice, vegetables/vegetable oil, liquor, and beans/nuts/soy. Among non-seafood consumers, higher THg was significantly associated with mixed rice dishes, vegetables/vegetable oil, liquor, and approached statistical significance with wine (p < 0.10); higher MeHg was significantly associated with wine and higher UHg was significantly associated with mixed rice dishes. Fish/seafood consumption is the strongest dietary predictor of mercury biomarker concentrations; however, consumption of wine, rice, vegetables/vegetable oil, or liquor may also contribute, especially among non-seafood consumers.

Manganese (Mn) is a neurotoxicant that many workers are exposed to daily. There is limited knowledge about how changes in exposure levels impact measures in magnetic resonance imaging (MRI). We hypothesized that changes in Mn exposure would be reflected by changes in the MRI relaxation rate R1 and thalamic γ-aminobutyric acid (GABAThal). As part of a prospective cohort study, 17 welders were recruited and imaged on 2 separate occasions approximately 2 years apart. MRI relaxometry was used to assess changes of Mn accumulation in the brain. Additionally, GABA was measured using magnetic resonance spectroscopy in the thalamic and striatal regions of the brain. Air Mn exposure ([Mn]Air) and cumulative exposure indexes of Mn (Mn-CEI) for the past 3 months (Mn-CEI3M), past year (Mn-CEI12M), and lifetime (Mn-CEILife) were calculated using personal air sampling and a comprehensive work history, whereas toenails were collected for analysis of internal Mn body burden. Finally, welders' motor function was examined using the Unified Parkinson's Disease Rating Scale (UPDRS). Median exposure decreased for all exposure measures between the first and second scan. ΔGABAThal was significantly correlated with ΔMn-CEI3M (ρ = 0.66, adjusted p = .02), ΔMn-CEI12M (ρ = 0.70, adjusted p = .006), and Δ[Mn]Air (ρ = 0.77, adjusted p = .002). ΔGABAThal significantly decreased linearly with ΔMn-CEI3M (quantile regression, β = 15.22, p = .02) as well as Δ[Mn]Air (β = 1.27, p = .04). Finally, Mn-CEILife interacted with Δ[Mn]Air in the substantia nigra where higher Mn-CEILife lessened the ΔR1 per Δ[Mn]Air (F-test, p = .005). Although R1 and GABA changed with Mn exposure, UPDRS was unaffected. In conclusion, our study shows that effects from changes in Mn exposure are reflected in thalamic GABA levels and brain Mn levels, as measured by R1, in most brain regions., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The aim of this study is to determine the association between length of time in the USA with blood lead (BPb)., Design: Population-based cross-sectional study using data from the 2013-2016 National Health and Nutrition Examination Survey., Setting: USA., Participants: 5933 men and women (≥15 years); subgroups of men only (n=2867), women only (n=3064) and women of childbearing age (15-45 years) (n=1580)., Primary and Secondary Outcomes: The primary outcome was BPb concentration. The main exposure variable was self-reported number of years spent in the USA, categorised as: born in the USA; 0-4 years; 5-9 years; 10-19 years and ≥20 years. We used linear regression models adjusted for race/ethnicity, education, blood cotinine, age, sex (as appropriate) and accounted for complex survey design., Results: Women of childbearing age who have lived 0-4 years in the USA have, on average, a 54% (95% CI 36% to 75%) higher BPb compared with women born in the USA. Corresponding results for all women, men and the entire population were 49% (95% CI 34% to 66%), 49% (95% CI 28% to 75%) and 49% (95% CI 33% to 66%), respectively. Similar, statistically significant, results were observed for other time periods (5-9 years, 10-19 years and ≥20 years); the magnitude of the association decreased with increasing time in the USA., Conclusions: This study provides additional evidence that newcomers to the USA may be a population at higher risk of elevated BPb., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Occupational manganese (Mn) exposure has been associated with cognitive and olfactory dysfunction; however, few studies have incorporated cumulative biomarkers of Mn exposure such as bone Mn (BnMn). Our goal was to assess the cross-sectional association between BnMn, blood Mn (BMn), and fingernail Mn (FMn) with cognitive and olfactory function among Mn-exposed workers. A transportable in vivo neutron activation analysis (IVNAA) system was designed and utilized to assess BnMn among 60 Chinese workers. BMn and FMn were measured using inductively coupled plasma mass spectrometry. Cognitive and olfactory function was assessed using Animal and Fruit Naming tests, World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test (AVLT) and the University of Pennsylvania Smell Identification Test (UPSIT). Additional data were obtained via questionnaire. Regression models adjusted for age, education, factory of employment, and smoking status (UPSIT only), were used to assess the relationship between Mn biomarkers and test scores. In adjusted models, increasing BnMn was significantly associated with decreased performance on average AVLT scores [β (95% confidence interval (CI)) = -0.65 (-1.21, -0.09)] and Animal Naming scores [β (95% CI) = -1.54 (-3.00, -0.07)]. Increasing FMn was significantly associated with reduced performance measured by the average AVLT [β (95% CI) = -0.35 (-0.70, -0.006)] and the difference in AVLT scores [β (95% CI) = -0.40 (-0.77, -0.03)]. BMn was not significantly associated with any test scores; no significant associations were observed with Fruit Naming or UPSIT tests. BnMn and FMn, but not BMn, are associated with cognitive function in Mn-exposed workers. None of the biomarkers were significantly associated with olfactory function., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Previous studies suggest that cumulative lead exposure is associated with cognitive decline, but its relation with Alzheimer's disease (AD) remains unclear. Therefore, this study investigated the longitudinal association between blood lead level (BLL) and AD mortality., Methods: This study included 8,080 elders (60 years or older) with BLL data from the 1999 to 2008 US National Health and Nutrition Examination Survey. Mortality was determined from linked 1999-2014 National Death Index data. A causal diagram presented causal assumptions and identified a sufficient set of confounders: age, sex, poverty, race/ethnicity, and smoking. Cox proportional hazard models were used to determine the association between BLL and subsequent AD mortality. Impacts of competing risks and design effect were also assessed. Adjusted hazard rate ratio (HRR) and 95% confidence interval (CI) were reported., Results: Follow-up ranged from <1 to 152 months (median, 74). Eighty-one participants died from AD over 632,075 total person-months at risk. An increase in BLL was associated with an increase in AD mortality after adjusting for identified confounders. We estimated that those with BLL of 1.5 and 5 μg/dl had 1.2 (95% CI = 0.70, 2.1) and 1.4 (95% CI = 0.54, 3.8) times the rate of AD mortality compared to those with BLL of 0.3 μg/dl, respectively, after accounting for competing risks. Adjusted HRRs were 1.5 (95% CI = 0.81, 2.9) and 2.1 (95% CI = 0.70, 6.3), respectively, after considering design effect., Conclusions: This longitudinal study demonstrated a positive, albeit not statistically significant, association between BLL and AD mortality after adjustment for competing risks or design effect., Competing Interests: Sponsorships or competing interests that may be relevant to content are disclosed at the end of the article.

Background: Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment., Methods: We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk., Findings: Among 23 601 survivors with a median follow-up of 21 years (IQR 15-25), the 20-year cumulative incidence of at least one grade 3-5 chronic condition decreased significantly from 33·2% (95% CI 32·0-34·3) in those diagnosed 1970-79 to 29·3% (28·4-30·2; p<0·0001) in 1980-89, and 27·5% (26·4-28·6; p=0·012 vs 1980-89) in 1990-99. By comparison, the 20-year cumulative incidence of at least one grade 3-5 condition in 5051 siblings was 4·6% (95% CI 3·9-5·2). The 15-year cumulative incidence of at least one grade 3-5 condition was lower for survivors diagnosed 1990-99 compared with those diagnosed 1970-79 for Hodgkin lymphoma (17·7% [95% CI 15·0-20·5] vs 26·4% [23·8-29·1]; p<0·0001), non-Hodgkin lymphoma (16·9% [14·0-19·7] vs 23·8% [19·9-27·7]; p=0.0053), astrocytoma (30·5% [27·8-33·2] vs 47·3% [42·9-51·7]; p<0·0001), Wilms tumour (11·9% [9·5-14·3] vs 17·6% [14·3-20·8]; p=0·034), soft tissue sarcoma (28·3% [23·5-33·1] vs 36·5% [31·5-41·4]; p=0·021), and osteosarcoma (65·6% [60·6-70·6] vs 87·5% [84·1-91·0]; p<0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3-5 condition was higher (1990-99 vs 1970-79) for medulloblastoma or primitive neuroectodermal tumour (58·9% [54·4-63·3] vs 42·9% [34·9-50·9]; p=0·00060), and neuroblastoma (25·0% [21·8-28·2] vs 18·0% [14·5-21·6]; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3-5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64-0·92; HR with treatment in the model=0·89, 95% CI 0·72-1·11; p mediation =0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95% CI 0·65-0·85; HR with treatment=0·91, 95% CI 0·73-1·12; p mediation =0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970-79 to survivors diagnosed 1990-99 were noted for endocrinopathies (5·9% [5·3-6·4] vs 2·8% [2·5-3·2]; p<0·0001), subsequent malignant neoplasms (2·7% [2·3-3·1] vs 1·9% [1·6-2·2]; p=0·0033), musculoskeletal conditions (5·8% [5·2-6·4] vs 3·3% [2·9-3·6]; p<0·0001), and gastrointestinal conditions (2·3% [2·0-2·7] vs 1·5% [1·3-1·8]; p=0·00037), while hearing loss increased (3·0% [2·6-3·5] vs 5·7% [5·2-6·1]; p<0·0001)., Interpretation: Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population., Funding: National Cancer Institute and the American Lebanese-Syrian Associated Charities., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Although secondary hemophagocytic lymphohistiocytosis (HLH) has been reported in children with critical illness of various etiologies, it has not been reported in patients with febrile infection-related epilepsy syndrome (FIRES). We describe a series of patients with concurrent HLH and FIRES in an effort to establish common pathophysiologic abnormalities., Methods: Five patients with FIRES who were assessed for HLH were identified from a neurocritical care database. All were previously healthy and had extensive diagnostic testing. All had clinical deterioration with multiorgan dysfunction prompting HLH screening 20-29 days after hospitalization. Markers for inflammatory dysregulation were assessed in cerebrospinal fluid (CSF) and serum at various time points. Outcomes were assessed 6 months after presentation., Results: Three patients met clinical criteria for secondary HLH. Elevation of specific cytokines/chemokines was variable. CSF neopterin, high mobility group box 1 (HMGB1), and C-X-C motif chemokine ligand 8 (CXCL8) were significantly elevated in all. Interleukin-1β (IL-1β) and IL-18 were not elevated in any of the samples. Treatment and outcomes were variable., Significance: We describe 3 patients with HLH and FIRES. The co-occurrence of these 2 rare disorders suggests the possibility of a common immune dysregulation phenotype prolonging epileptogenesis. HLH screening in critically ill patients with FIRES may yield a broader understanding of shared inflammatory processes., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Manganese (Mn) exposure can result in parkinsonism. However, understanding of manganese neurotoxicity has been limited by the lack of a cumulative Mn biomarker. Therefore, the current goal was to develop Mn cumulative exposure indices (MnCEI), an established method to estimate cumulative exposure, and determine associations of MnCEI with blood Mn (BMn), fingernail Mn (FMn), and bone Mn (BnMn). We completed a cross-sectional study of 60 male Chinese workers. Self-reported occupational history was used to create two MnCEIs reflecting the previous 16 years (MnCEI 16 ) and total work history (MnCEI TOT ). An in vivo neutron activation analysis system was used to quantify BnMn. BMn and FMn were measured using ICP-MS. Mean (standard deviation) MnCEI TOT and MnCEI 16 were 37.5 (22.0) and 25.0 (11.3), respectively. Median (interquartile range) BMn, FMn, and BnMn were 14.1 (4.0) &mu;g/L, 13.5 (58.5) &mu;g/g, and 2.6 (7.2) &mu;g/g dry bone, respectively. MnCEI 16 was significantly correlated with FMn (Spearman&rsquo;s &rho; = 0.44; p = 0.02), BnMn ( &rho; = 0.44; p < 0.01), and MnCEI TOT ( &rho; = 0.44; p < 0.01). In adjusted regression models, MnCEI 16 was significantly associated with BnMn (&beta; = 0.03; 95% confidence interval = 0.001, 0.05); no other biomarkers were associated with MnCEI. This suggests BnMn may be a useful biomarker of the previous 16 years of Mn exposure, but larger studies are recommended.

Background: Survivors of childhood central nervous system (CNS) tumors experience high rates of treatment-related neurologic sequelae. Whether survivors continue to be at increased risk for new events as they age is unknown., Methods: Adverse neurologic health conditions in 5-year survivors of CNS tumors from the Childhood Cancer Survivor Study (n = 1876) were evaluated longitudinally at a median 23.0 years from diagnosis (range, 5.1-38.9), median age at last evaluation 30.3 years (range, 6.1-56.4). Multivariable regression estimated hazard ratios (HRs) and 95% CIs., Results: From 5 to 30 years post diagnosis, cumulative incidence increased for seizures from 27% to 41%, motor impairment 21% to 35%, and hearing loss 9% to 23%. Risks were elevated compared with siblings (eg, seizures HR: 12.7; 95% CI: 9.6-16.7; motor impairment HR: 7.6; 95% CI: 5.8-9.9; hearing loss HR: 18.4; 95% CI: 13.1-25.9). Regional brain doses of radiation therapy were associated with development of new deficits (eg, frontal ≥50 Gy and motor impairment HR: 2.0; 95% CI: 1.2-3.4). Increased risk for motor impairment was also associated with tumor recurrence (HR: 2.6; 95% CI: 1.8-3.8), development of a meningioma (HR: 2.3; 95% CI: 0.9-5.4), and stroke (HR: 14.9; 95% CI: 10.4-21.4). Seizure risk was doubled by recurrence (HR: 2.3; 95% CI: 1.6-3.2), meningioma (HR: 2.6; 95% CI: 1.1-6.5), and stroke (HR: 2.0; 95% CI: 1.1-3.4)., Conclusions: CNS tumor survivors remain at risk for new-onset adverse neurologic events across their lifespans at a rate greater than siblings. Cranial radiation, stroke, tumor recurrence, and development of meningioma were independently associated with late-onset adverse neurologic sequelae., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

We used neutron activation analysis (NAA) to measure hand bone manganese (BnMn) in 19 adult males. Median BnMn was 0.89µg/g dry bone (interquartile range = 1.07). After adjustment for age and occupation, higher ln(BnMn) was significantly associated with lower manual dexterity based on the Purdue Pegboard assembly task: β = -1.77, standard error = 0.79, p = 0.04. Due to the small sample size, these results should be interpreted cautiously. BnMn appears to be a promising biomarker, and should be further studied., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose of Review: This review describes published literature providing evidence for financial conflicts of interest in environmental and occupational health research. Secondary goals were to describe evidence that (a) utilized quantitative methods to evaluate the association of conflicts with study outcomes, and (b) assessed undisclosed as well as disclosed conflicts of interest., Recent Findings: Forty-three studies were identified which contained descriptions of the impact of financial conflicts of interest on research results; 11 of these conducted quantitative analyses to demonstrate these relationships. All 11 articles which quantified associations identified significant associations of the presence of financial conflicts of interest with study findings. In studies which measured undisclosed conflicts, these comprised a substantial proportion of all conflicts. Suggestions for improving understanding and interpretation of research results are presented.

Prior studies addressing associations between mercury and blood pressure have produced inconsistent findings; some of this may result from measuring total instead of speciated mercury. This cross-sectional study of 263 pregnant women assessed total mercury, speciated mercury, selenium, and n-3 polyunsaturated fatty acids in umbilical cord blood and blood pressure during labor and delivery. Models with a) total mercury or b) methyl and inorganic mercury were evaluated. Regression models adjusted for maternal age, race/ethnicity, prepregnancy body mass index, neighborhood income, parity, smoking, n-3 fatty acids and selenium. Geometric mean total, methyl, and inorganic mercury concentrations were 1.40µg/L (95% confidence interval: 1.29, 1.52); 0.95µg/L (0.84, 1.07); and 0.13µg/L (0.10, 0.17), respectively. Elevated systolic BP, diastolic BP, and pulse pressure were found, respectively, in 11.4%, 6.8%, and 19.8% of mothers. In adjusted multivariable models, a one-tertile increase of methyl mercury was associated with 2.83mmHg (0.17, 5.50) higher systolic blood pressure and 2.99mmHg (0.91, 5.08) higher pulse pressure. In the same models, an increase of one tertile of inorganic mercury was associated with -1.18mmHg (-3.72, 1.35) lower systolic blood pressure and -2.51mmHg (-4.49, -0.53) lower pulse pressure. No associations were observed with diastolic pressure. There was a non-significant trend of higher total mercury with higher systolic blood pressure. We observed a significant association of higher methyl mercury with higher systolic and pulse pressure, yet higher inorganic mercury was significantly associated with lower pulse pressure. These results should be confirmed with larger, longitudinal studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Decreased total testosterone (TT) is the recommended metric to identify age-related hypogonadism. However, average TT and the extent to which it varies by age, can vary substantially among different populations. Population-specific reference ranges are needed to understand normal versus abnormal TT levels. Therefore, the goal for this study was to describe androgen concentrations and their correlates among Western Chinese men. We completed a population-based, cross-sectional study including 227 young adults (YA) (20-39 years) and 939 older adults (OA) (40-89 years). We measured TT, sex-hormone binding globulin (SHBG), luteinizing hormone (LH), testosterone secreting index (TSI), and calculated free testosterone (cFT). Reference ranges for this population were determined using average YA concentrations. Multivariable regression models were used to predict hormone concentrations adjusting for age, waist-to-height ratio (WHR), marital status, education, occupation, smoking, alcohol, blood glucose, and blood pressure. Among OA, 3.8% had low TT, 15.2% had low cFT, 26.3% had low TSI, 21.6% had high SHBG, and 6.1% had high LH. Average cFT was significantly lower in OA (0.30 nmol/L; standard deviation (SD): 0.09) versus YA (0.37; SD: 0.11) but TT was not different in OA (16.82 nmol/L; SD: 4.80) versus YA (16.88; SD: 5.29). In adjusted models increasing age was significantly associated with increased SHBG or LH, and decreased cFT or TSI; however, TT was not significantly associated with age (β = 0.02 nmol/L; 95% confidence interval (CI): -0.01, 0.04). Higher WHR was associated with significantly decreased TT, SHBG, TSI, and LH. The only variable significantly related to cFT was age (β = -0.0033; 95% CI:-0.0037, -0.0028); suggesting that cFT measurements would not be confounded by other lifestyle factors. In conclusion, cFT, but not TT, varies with age in this population, suggesting cFT may be a better potential marker for age-related androgen deficiency than TT among Western Chinese men., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Confusion has surrounded the description of post-operative mutism and associated morbidity in pediatric patients with cerebellar tumors for years. The heterogeneity of definitions and diagnostic features has hampered research progress within the field, and to date, no international guidelines exist on diagnosis, prevention, treatment, or follow-up of this debilitating condition. An international group of clinicians and researchers from multiple relevant disciplines recently formed a cohesive panel to formulate a new working definition and agree upon standardized methods for diagnosis and follow-up., Methods: Consensus was obtained using the modified nominal group technique, involving four rounds of online Delphi questionnaires interspersed with a structured consensus conference with lectures, group work, and open discussion sessions., Results: A new, proposed definition of "post-operative pediatric CMS" was formed, preliminary recommendations for diagnostic and follow-up procedures were created, two working groups on a new scoring scale and risk prediction and prevention were established, and areas were identified where further information is needed., Discussion: The consensus process was motivated by desire to further research and improve quality of life for pediatric brain tumor patients. The Delphi rounds identified relevant topics and established basic agreement, while face-to-face engagement helped resolve matters of conflict and refine terminology. The new definition is intended to provide a more solid foundation for future clinical and research work. It is thought as a consensus for moving forward and hopefully paves the way to developing a standard approach to this challenging problem with the advent of better scoring methods and ultimate goal of reducing the risk of CMS.

A 3-year-old boy with sickle cell anemia (SCA) presented with progressive daily emesis and was found to have an anaplastic ependymoma. Radiation therapy and chemotherapy are usually employed after subtotal resections of anaplastic ependymomas, although the benefits from chemotherapy are unclear. To mitigate the risks of adjuvant treatment in this patient at risk for SCA-associated vasculopathy, renal impairment, and other end-organ damage, proton beam irradiation without chemotherapy was chosen. Scheduled packed red blood cell transfusions were instituted to maintain sickle hemoglobin levels less than 30%. This case highlights treatment complexities for malignant brain tumors in patients predisposed to treatment-related adverse effects., (© 2015 Wiley Periodicals, Inc.)

Background: Methylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions., Objective: Our objective was to assess the relationship between MeHg and fetal growth as well as the potential for confounding or interaction of this relationship from speciated mercury, fatty acids, selenium, and sex., Methods: This cross-sectional study includes 271 singletons born in Baltimore, Maryland, 2004-2005. Umbilical cord blood was analyzed for speciated mercury, serum omega-3 highly unsaturated fatty acids (n-3 HUFAs), and selenium. Multivariable linear regression models controlled for gestational age, birth weight, maternal age, parity, prepregnancy body mass index, smoking, hypertension, diabetes, selenium, n-3 HUFAs, and inorganic mercury (IHg)., Results: Geometric mean cord blood MeHg was 0.94 μg/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, βln(MeHg) = -0.045 (g/cm(3)) × 100 (95% CI: -0.084, -0.005). There was no evidence of a MeHg × sex interaction with ponderal index. Contrastingly, there was evidence of a MeHg × n-3 HUFAs interaction with birth length [among low n-3 HUFAs, βln(MeHg) = 0.40 cm, 95% CI: -0.02, 0.81; among high n-3 HUFAs, βln(MeHg) = -0.15, 95% CI: -0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, βln(MeHg) = 0.01 cm, 95% CI: -0.27, 0.29; among high n-3 HUFAs, βln(MeHg) = -0.37, 95% CI: -0.63, -0.10; p-interaction = 0.042]. The association of MeHg with birth weight and ponderal index was affected by n-3 HUFAs, selenium, and IHg. For birth weight, βln(MeHg) without these variables was -16.8 g (95% CI: -75.0, 41.3) versus -29.7 (95% CI: -93.9, 34.6) with all covariates. Corresponding values for ponderal index were -0.030 (g/cm(3)) × 100 (95% CI: -0.065, 0.005) and -0.045 (95% CI: -0.084, -0005)., Conclusion: We observed an association of increased MeHg with decreased ponderal index. There is evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies.

Current consensus guidelines recommending physical and cognitive rest until a patient is asymptomatic after a sports concussion (ie, a mild traumatic brain injury) are being called into question, particularly for patients who are slower to recover and in light of preclinical and clinical research demonstrating that exercise aids neurorehabilitation. The pathophysiological response to mild traumatic brain injury includes a complex neurometabolic cascade of events resulting in a neurologic energy deficit. It has been proposed that this energy deficit leads to a period of vulnerability during which the brain is at risk for additional injury, explains why early postconcussive symptoms are exacerbated by cognitive and physical exertion, and is used to rationalize absolute rest until all symptoms have resolved. However, at some point, rest might no longer be beneficial and exercise might need to be introduced. At both extremes, excessive exertion and prolonged avoidance of exercise (physical and mental) have negative consequences. Individuals who have experienced a concussion need guidance for avoidance of triggers of severe symptoms and a plan for graduated exercise to promote recovery as well as optimal functioning (physical, educational, and social) during the postconcussion period., (© The Author(s) 2015.)

Background: Autonomic dysfunction in pediatric patients with acquired brain injury is often encountered and greatly understudied. We sought to identify the incidence of Paroxysmal Sympathetic Hyperactivity (PSH) in critically ill pediatric patients with meningoencephalitis and encephalitis, associated risk factors and influence on outcome., Methods: Children admitted to the pediatric intensive care unit (PICU) with a diagnosis of meningoencephalitis and/or encephalitis were identified from a single institution Neurocritical Care database. The patients were stratified as having a bacterial or non-bacterial cause of their meningoencephalitis/encephalitis. Data from their hospitalization was supplemented with a retrospective review of the electronic medical record. PSH was defined as episodic lability in heart rate and/or blood pressure, hyperthermia, diaphoresis, dystonic posturing, tachypnea and/or agitation without any other cause. Statistical analysis was performed using t-test and chi-squared to compare outcomes and risk factors between patients with PSH and without., Results: PSH was found in 41 % of children studied. Subgroup analysis revealed patients with non-bacterial encephalitis were more likely to experience PSH (51 %) as compared to those with bacterial causes (27 %). Fever and/or seizures on presentation and female gender were associated with higher occurrence of PSH but only in the non-bacterial etiology group. There were trends toward increased length of PICU and overall hospital stay for patients with PSH., Conclusions: PSH was found in a high percentage of our patients with significant variation in risk factors and outcome noted between patients with bacterial and nonbacterial causes of their meningoencephalitis/encephalitis.

Background: Human exposure to the widespread environmental contaminant mercury is a known risk factor for common diseases such as cancer, cardiovascular disease and neurological disorders through poorly characterized mechanisms. Evidence suggests mercury exposure may alter DNA methylation levels, but to date, the effects in early life on a genome-wide scale have not been investigated., Methods: A study sample of 141 newborns was recruited in Baltimore, MD, USA and total mercury and methylmercury were measured in cord blood samples. We quantified genome-wide DNA methylation data using CHARM 2.0, an array-based method, and used region-finding analyses to identify concentration-associated differentially methylated regions (DMRs). To test for replication of these identified DMRs in the pilot, or Vanguard, phase of the National Children's Study (NCS), we compared bisulfite-pyrosequenced DNA at candidate regions from 85 whole cord blood samples with matched first trimester maternal mercury concentration measures., Results: Total mercury concentration was associated with methylation at DMRs inside ANGPT2 and near PRPF18 genes [false discovery rate (FDR) < 0.05], as well as DMRs near FOXD2 and within TCEANC2 (FDR< 0.1) genes. Methylmercury concentration was associated with an overlapping DMR within TCEANC2 (FDR< 0.05). In NCS replication analyses, methylation levels at three of four cytosine-guanine DNA dinucleotides (CpG sites) within the TCEANC2 DMR were associated with total mercury concentration (P < 0.05), and this association was diminished after adjusting for estimated cell proportions., Conclusions: Evidence for an association between mercury and DNA methylation at the TCEANC2 region was found, which may represent a mercury-associated shift in cord blood cell composition or a change in methylation within blood cell types. Further confirmatory studies are needed., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Purpose of Review: Pediatric brain tumors differ from those arising in adulthood. This article discusses the presentation, location, histology, new molecular understanding, therapy, and outcome of brain tumors in children., Recent Findings: Improved biological understanding of pediatric brain tumors is resulting in new molecular-based classification and the development of rationally designed therapeutics., Summary: The presentation of a pediatric brain tumor is dependent on the type of tumor, its location in the nervous system, and the age of the child. Diagnostic workup varies depending on the location of the tumor and the tumor's propensity to disseminate in the nervous system. Survival has improved for pediatric brain tumors, particularly medulloblastoma, as a result of improved surgical techniques and rational use of postoperative radiation and chemotherapy. For medulloblastoma, recent studies have sought to maintain or improve survival while decreasing neurologic sequelae, particularly from radiation in young children. For other childhood brain tumor types, improvements in outcome are not as clear-cut. New molecular insights will likely alter classification, risk stratification, and therapy in the near future.

Vincristine, a critical component of combination chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL), can lead to vincristine-induced peripheral neuropathy (VIPN). Longitudinal VIPN assessments were obtained over 12 months from newly diagnosed children with ALL (N = 128) aged 1-18 years who received vincristine at one of four academic children's hospitals. VIPN assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine (TNS©-PV), National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE©), Balis© grading scale, and Pediatric Neuropathic Pain Scale©-Five (PNPS©-5). Of children who provided a full TNS©-PV score, 85/109 (78%) developed VIPN (TNS©-PV ≥4). Mean TNS©-PV, grading scale, and pain scores were low. CTCAE©-derived grades 3 and 4 sensory and motor VIPN occurred in 1.6%/0%, and 1.9%/0% of subjects, respectively. VIPN did not resolve in months 8-12 despite decreasing dose density. VIPN was worse in older children. Partition cluster analysis revealed 2-3 patient clusters; one cluster (n = 14) experienced severe VIPN. In this population, VIPN occurs more commonly than previous research suggests, persists throughout the first year of treatment, and can be severe., (© 2015 Peripheral Nerve Society.)

Altered levels of selenium and copper have been linked with altered cardiovascular disease risk factors including changes in blood triglyceride and cholesterol levels. However, it is unclear whether this can be observed prenatally. This cross-sectional study includes 274 singleton births from 2004 to 2005 in Baltimore, Maryland. We measured umbilical cord serum selenium and copper using inductively coupled plasma mass spectrometry. We evaluated exposure levels vis-à-vis umbilical cord serum triglyceride and total cholesterol concentrations in multivariable regression models adjusted for gestational age, birth weight, maternal age, race, parity, smoking, prepregnancy body mass index, n-3 fatty acids and methyl mercury. The percent difference in triglycerides comparing those in the highest v. lowest quartile of selenium was 22.3% (95% confidence interval (CI): 7.1, 39.7). For copper this was 43.8% (95% CI: 25.9, 64.3). In multivariable models including both copper and selenium as covariates, copper, but not selenium, maintained a statistically significant association with increased triglycerides (percent difference: 40.7%, 95% CI: 22.1, 62.1). There was limited evidence of a relationship of increasing selenium with increasing total cholesterol. Our findings provide evidence that higher serum copper levels are associated with higher serum triglycerides in newborns, but should be confirmed in larger studies.

Purpose: To describe how the quality of life (QOL) discussion in childhood medulloblastoma (MB) relates to treatment developments, survival and sequelae from 1920 to 2014., Methods: Articles containing "childhood medulloblastoma" and "quality of life" were identified in PubMed. Those containing phrases pertaining to psychological, emotional, behavioral or social adjustment in the title, abstract or keywords were selected. Inclusion of relevant older publications was assured by cross-checking references., Results: 1920-1930s: suction, electro-surgery, kilovolt (KV) irradiation. Survival = months. Focus on operative mortality, symptoms and survival. 1940s: radiotherapy improved. 1950s: chemotherapy and intubation. Survival = years. Opinions oscillated between optimism/awareness of physical sequelae of radiotherapy. 1960s: magnified vision, ventriculo-peritoneal (VP) shunts, megavolt (MV) irradiation. Long-term survival shifted the attention towards neurological problems, disability and carcinogenesis of radiotherapy. 1970s: CT, microscope, bipolar coagulation, shunt filters, neuroanesthesia, chemotherapy trials and staging studies. Operative mortality decreased and many patients (re)entered school; emphasis on neuropsychological sequelae, IQ and academic performance. 1980s: magnetic resonance imaging (MRI), Cavitron ultrasonic aspiration (CUSA), laser surgery, hyper-fractionated radiotherapy (HFRT). Cerebellar mutism, psychological and social issues. 1990s: pediatric neurosurgery, proton beams, stem cell rescue. Reflections on QOL as such. 21st century: molecular genetics. Premature aging, patterns of decline, risk- and resilience factors., Discussion: QOL is a critical outcome measure. Focus depends on survival and sequelae, determined after years of follow-up. Detailed measurements are limited by time, money and human resources, and self-reporting questionnaires represent a crude measure limited by subjectivity. Therapeutic improvements raise the question of QOL versus cure. QOL is a potential primary research endpoint; multicenter international studies are needed, as are web-based tools that work across cultures.

Longitudinal imaging and quantitative genetic studies have both provided important insights into the nature of human brain development. In the present study we combine these modalities to obtain dynamic anatomical maps of the genetic contributions to cortical thickness through childhood and adolescence. A total of 1,748 anatomic MRI scans from 792 healthy twins and siblings were studied with up to eight time points per subject. Using genetically informative latent growth curve modeling of 81,924 measures of cortical thickness, changes in the genetic contributions to cortical development could be visualized across the age range at high resolution. There was highly statistically significant (P < 0.0001) genetic variance throughout the majority of the cerebral cortex, with the regions of highest heritability including the most evolutionarily novel regions of the brain. Dynamic modeling of changes in heritability over time demonstrated that the heritability of cortical thickness increases gradually throughout late childhood and adolescence, with sequential emergence of three large regions of high heritability in the temporal poles, the inferior parietal lobes, and the superior and dorsolateral frontal cortices.

Early life lead exposure may alter immune function and predispose a child to develop asthma. In an initial exploration of this hypothesis, we examined the association between blood lead, and serum immunoglobulin E (IgE), eosinophils, and asthma prevalence in a cross-sectional study of 1788 children from the National Health and Nutrition Examination Survey 2005-2006. Geometric mean blood lead, serum IgE, and percent eosinophils were 1.13 μg/dL (95% confidence interval (CI): 1.04, 1.22), 46.3 kU/L (95% CI: 40.3, 53.1), and 2.82 percent (95% CI 2.67, 2.98), respectively. Prevalence of asthma, atopic asthma, and atopy were 11.8% (95% CI: 9.5, 14.2), 8.1% (6.2, 9.9), and 44.4% (40.1, 48.7), respectively. Regression models controlled for season, age, sex, race/ethnicity, education, passive smoke exposure, and body mass index. Based on these models, there was an 11.1% (95% CI: 5.6, 16.9) increase in IgE and a 4.9% (95% CI: 2.3, 7.6) increase in eosinophils per 1 μg/dL increase in blood lead. In independent stratified analyses, lead was found to increase IgE and eosinophils among non-Hispanic whites, but not other children; and stronger associations were observed among children who lived with a smoker vs. not. Lead was not associated with asthma, atopic asthma, or general atopy. This study provides additional evidence of a cross-sectional association between lead with IgE and new evidence for eosinophils. This may be a mechanism for development of downstream allergic disease. The mechanisms that determine ultimate development of allergic disease are currently unknown, but are the focus of ongoing studies., (Copyright © 2013 Elsevier GmbH. All rights reserved.)