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Article ; Online: Adaptive-mixture-categorization (AMC)-based g-computation and its application to trace element mixtures and bladder cancer risk

Siting Li / Margaret R. Karagas / Brian P. Jackson / Michael N. Passarelli / Jiang Gui

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 9

Abstract: Abstract Several new statistical methods have been developed to identify the overall impact of an exposure mixture on health outcomes. Weighted quantile sum (WQS) regression assigns the joint mixture effect weights to indicate the overall association of ... ...

Abstract	Abstract Several new statistical methods have been developed to identify the overall impact of an exposure mixture on health outcomes. Weighted quantile sum (WQS) regression assigns the joint mixture effect weights to indicate the overall association of multiple exposures, and quantile-based g-computation is a generalized version of WQS without the restriction of directional homogeneity. This paper proposes an adaptive-mixture-categorization (AMC)-based g-computation approach that combines g-computation with an optimal exposure categorization search using the F statistic. AMC-based g-computation reduces variance within each category and retains the variance between categories to build more powerful predictors. In a simulation study, the performance of association analysis was improved using categorizing by AMC compared with quantiles. We applied this method to assess the association between a mixture of 12 trace element concentrations measured from toenails and the risk of non-muscle invasive bladder cancer. Our findings suggested that medium-level (116.7–145.5 μg/g) vs. low-level (39.5–116.2 μg/g) of toenail zinc had a statistically significant positive association with bladder cancer risk.
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Arsenic metabolism, diabetes prevalence, and insulin resistance among Mexican Americans

Margaret C. Weiss / Yu-Hsuan Shih / Molly Scannell Bryan / Brian P. Jackson / David Aguilar / Eric L. Brown / Goo Jun / Craig L. Hanis / Maria Argos / Robert M. Sargis

Environmental Advances, Vol 12, Iss , Pp 100361- (2023)

A mendelian randomization approach

2023

Abstract: Background: Differences in arsenic metabolism capacity may influence risk for type 2 diabetes, but the mechanistic drivers are unclear. We evaluated the associations between arsenic metabolism with overall diabetes prevalence and with static and dynamic ... ...

Abstract	Background: Differences in arsenic metabolism capacity may influence risk for type 2 diabetes, but the mechanistic drivers are unclear. We evaluated the associations between arsenic metabolism with overall diabetes prevalence and with static and dynamic measures of insulin resistance among Mexican Americans living in Starr County, Texas. Methods: We utilized data from cross-sectional studies conducted in Starr County, Texas, from 2010-2014. A Mendelian randomization approach was utilized to evaluate the associations between arsenic metabolism and type 2 diabetes prevalence using the intronic variant in the arsenic methylating gene, rs9527, as the instrumental variable for arsenic metabolism. To further assess mechanisms for diabetes pathogenesis, proportions of the urinary arsenic metabolites were employed to assess the association between arsenic metabolism and insulin resistance among participants without diabetes. Urinary biomarkers of arsenic metabolites were modeled as individual proportions of the total. Arsenic metabolism was evaluated both with a static outcome of insulin resistance, homeostatic measure of assessment (HOMA-IR), and a dynamic measure of insulin sensitivity, Matsuda Index. Results: Among 475 Mexican American participants from Starr County, higher metabolism capacity for arsenic is associated with higher diabetes prevalence driven by worse insulin resistance. Presence of the minor T allele of rs9527 is independently associated with an increase in the proportion of monomethylated arsenic (MMA%) and is associated with an odds ratio of 0.50 (95% CI: 0.24, 0.90) for type 2 diabetes. This association was conserved after potential covariate adjustment. Furthermore, among participants without type 2 diabetes, the highest quartile of MMA% was associated with 22% (95% CI: -33.5%, -9.07%) lower HOMA-IR and 56% (95% CI: 28.3%, 91.3%) higher Matsuda Index for insulin sensitivity. Conclusions: Arsenic metabolism capacity, indicated by a lower proportion of monomethylated arsenic, is associated with ...
Keywords	Arsenic ; Methylation ; Type 2 diabetes ; Insulin resistance ; Insulin sensitivity ; Endocrine disruptor ; Environmental sciences ; GE1-350
Subject code	571 ; 616
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Infant infections, respiratory symptoms, and allergy in relation to timing of rice cereal introduction in a United States cohort

Yuka Moroishi / Antonio J. Signes-Pastor / Zhigang Li / Kathryn L. Cottingham / Brian P. Jackson / Tracy Punshon / Juliette Madan / Kari Nadeau / Jiang Gui / Margaret R. Karagas

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 8

Abstract: Abstract Rice products marketed in the USA, including baby rice cereal, contain inorganic arsenic, a putative immunotoxin. We sought to determine whether the timing of introduction of rice cereal in the first year of life influences occurrence of ... ...

Abstract	Abstract Rice products marketed in the USA, including baby rice cereal, contain inorganic arsenic, a putative immunotoxin. We sought to determine whether the timing of introduction of rice cereal in the first year of life influences occurrence of infections, respiratory symptoms, and allergy. Among 572 infants from the New Hampshire Birth Cohort Study, we used generalized estimating equation, adjusted for maternal smoking during pregnancy, marital status, education attainment, pre-pregnancy body mass index, maternal age at enrollment, infant birth weight, and breastfeeding history. Among 572 infants, each month earlier of introduction to rice cereal was associated with increased risks of subsequent upper respiratory tract infections (relative risk, RR = 1.04; 95% CI: 1.00–1.09); lower respiratory tract infections (RR = 1.19; 95% CI: 1.02–1.39); acute respiratory symptoms including wheeze, difficulty breathing, and cough (RR = 1.10; 95% CI: 1.00–1.22); fever requiring a prescription medicine (RR = 1.22; 95% CI: 1.02–1.45) and allergy diagnosed by a physician (RR = 1.20; 95% CI: 1.06–1.36). No clear associations were observed with gastrointestinal symptoms. Our findings suggest that introduction of rice cereal earlier may influence infants’ susceptibility to respiratory infections and allergy.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nutrient-toxic element mixtures and the early postnatal gut microbiome in a United States longitudinal birth cohort

Hannah E. Laue / Yuka Moroishi / Brian P. Jackson / Thomas J. Palys / Juliette C. Madan / Margaret R. Karagas

Environment International, Vol 138, Iss , Pp - (2020)

2020

Abstract: Background: The infant microbiome contributes to health status across the lifespan, but environmental factors affecting microbial communities are poorly understood, particularly when toxic and essential elements interact. Objective: We aimed to identify ... ...

Abstract	Background: The infant microbiome contributes to health status across the lifespan, but environmental factors affecting microbial communities are poorly understood, particularly when toxic and essential elements interact. Objective: We aimed to identify the associations between a spectrum of other early-postnatal nutrient or toxic elemental exposures measured and the infant gut microbiome. Methods: Our analysis included 179 six-week-old infants from the New Hampshire Birth Cohort Study. Eleven elements were measured in infant toenail clippings. The gut microbiome was assessed using 16S rRNA V4-V5 hypervariable region targeted sequencing. Multivariable zero-inflated logistic normal regression (MZILN) was used to model the association between element concentrations and taxon relative abundance. To explore interactive and nonlinear associations between the exposures and specific taxa we employed Bayesian Kernel Machine Regression (BKMR). Effect modification by delivery mode, feeding mode, peripartum antibiotic exposure, and infant sex was assessed with stratified models. Results: We found a negative association between arsenic and microbial diversity in the full population that was accentuated among infants exposed to peripartum antibiotics. Arsenic, cadmium, copper, iron, lead, manganese, nickel, selenium, tin, and zinc were each associated with differences in at least one taxon in the full study population, with most of the related taxa belonging to the Bacteroides and Lactobacillales. In stratified analyses, mercury, in addition to the other elements, was associated with specific taxa. Bifidobacterium, which associated negatively with zinc in MZILN and BKMR models, had a quadratic association with arsenic concentrations. These associations varied with the concentration of the other element. Conclusions: Early postnatal toxic and nutrient elemental exposures are associated with differences in the infant microbiome. Further research is needed to clarify the whether these alterations are a biomarker of exposure or ...
Keywords	Environmental sciences ; GE1-350
Subject code	333
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Urine and toenail cadmium levels in pregnant women

Alexandra J. White / Katie M. O'Brien / Brian P. Jackson / Margaret R. Karagas

Environment International, Vol 118, Iss , Pp 86-

A reliability study

2018 Volume 91

Abstract: Background: Cadmium, as measured in human tissue, has been associated with numerous health outcomes. However, few studies have evaluated the reliability of cadmium measurements across different biologic samples. We evaluated toenail cadmium levels over ... ...

Abstract	Background: Cadmium, as measured in human tissue, has been associated with numerous health outcomes. However, few studies have evaluated the reliability of cadmium measurements across different biologic samples. We evaluated toenail cadmium levels over time and compared toenail cadmium to urinary cadmium. We also evaluated the relationship between biomarker concentrations and cigarette smoking, a known source of cadmium exposure. Methods: Cadmium was assessed in urine and toenail samples collected from 1338 pregnant women participating in the New Hampshire Birth Cohort Study. Each participant was asked to provide a urine and a toenail sample at enrollment (between 24 and 28 weeks gestation) and another toenail sample 2–8 weeks postpartum. Cadmium concentrations were determined using inductively-coupled plasma mass spectrometry. Spearman correlations were assessed for cadmium in the toenails across the two-time points and comparing toenail and urine levels. Smoking status was evaluated as a predictor of cadmium levels. Results: Toenail cadmium assessed during pregnancy and postpartum were modestly correlated (R = 0.3, p < 0.0001). However, urine and toenail cadmium levels were unrelated (R = −0.03, p = 0.46). Both toenail and urinary cadmium levels were associated with women's smoking status. Conclusion: Our findings suggest that both toenail and urinary cadmium concentrations reflect the major source of exposure – cigarette smoking. Toenail cadmium concentrations are modestly reproducible pre- and postpartum; but do not appear to be related to urinary cadmium and thus likely represent different windows and chronicity of exposure among pregnant women. Keywords: Cadmium, Pregnancy, Urine, Toenail, Reliability, Biomarker
Keywords	Environmental sciences ; GE1-350
Subject code	500
Language	English
Publishing date	2018-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article: Concentrations and speciation of arsenic in New England seaweed species harvested for food and agriculture

Taylor, Vivien F / Brian P. Jackson

Chemosphere. 2016 Nov., v. 163

2016

Abstract: A survey of arsenic (As) concentrations and speciation was conducted on 10 species of seaweed from commercial harvesters and from collection at two sites in New England. Concentrations of As ranged from 4 to 106Â mg/kg, mostly in the form of arsenosugars, ...

Abstract	A survey of arsenic (As) concentrations and speciation was conducted on 10 species of seaweed from commercial harvesters and from collection at two sites in New England. Concentrations of As ranged from 4 to 106Â mg/kg, mostly in the form of arsenosugars, with the distribution of arsenosugar analogs varying between taxa. In brown algae, As levels were correlated with phosphate concentrations, and arsenosugar speciation reflected differences in sulfur and phosphate concentrations between taxa. Several samples of the brown algae species Laminaria digitata contained significant levels of inorganic As (2.8â20Â mg/kg), the most toxic form of As. A weak acid extraction with microwave heating was compared with a weaker methanol: water extraction method, and found to give slightly higher extraction efficiency with comparable relative concentrations of inorganic As, supporting the use of this faster and simpler extraction method for monitoring. Seaweed is a niche dietary item in the U.S. but its popularity is increasing; it is also used in agriculture and livestock farming which provide potential indirect routes for human exposure. The presence of occasional high concentrations of iAs, as well as the lack of toxicity studies on organic As species, suggest that monitoring of these high As foods is warranted.
Keywords	Laminaria ; arsenic ; foods ; harvesters ; humans ; livestock farming ; macroalgae ; methanol ; microwave treatment ; monitoring ; phosphates ; sulfur ; surveys ; toxicity ; toxicity testing ; New England region ; United States
Language	English
Dates of publication	2016-11
Size	p. 6-13.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2016.08.004
Database	NAL-Catalogue (AGRICOLA)

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Article: Determination of Osmium Concentration and Isotope Composition at Ultra-low Level in Polar Ice and Snow

Seo, Ji-Hye / Brian P. Jackson / Erich C. Osterberg / Mukul Sharma

Analytical chemistry. 2018 Apr. 08, v. 90, no. 9

2018

Abstract: Here we use two chemical separation procedures to determine exceptionally low Os concentrations (∼10–15 g g–1) and Os isotopic composition in polar snow/ice. Approximately 50 g of meltwater is spiked with 190Os tracer solution and frozen at −20 °C in ... ...

Abstract	Here we use two chemical separation procedures to determine exceptionally low Os concentrations (∼10–15 g g–1) and Os isotopic composition in polar snow/ice. Approximately 50 g of meltwater is spiked with 190Os tracer solution and frozen at −20 °C in quartz-glass ampules. A mixture of H2O2 and HNO3 is then added, and the sample is heated to 300 °C at 100 bar. This allows tracer Os to be equilibrated with the sample as all Os species are oxidized to OsO4. The resulting OsO4 is separated using either distillation (Method-I) or solvent-extraction (Method-II), purified, and measured using negative thermal ionization mass spectrometry (N-TIMS). A new technique is presented that minimizes Re and Os blanks of the Pt filaments used in N-TIMS. We analyze snow collected from Summit, Greenland during 2009, 2014, and 2017. We find that the average Os concentration of the snow is 0.459 ± 0.018 (95% C.I.) fg g–1 corresponding to an Os flux of 0.0579 ± 0.0023 (95% C.I.) fmol cm–2 yr–1. The average R(187Os/188Os) ratio of the Summit snow is 0.264 ± 0.026 (95% C.I.). Assuming that the volcanic source is negligible, the average ratio indicates that about 0.0518 ± 0.0040 (95% C.I.) fmol cm–2 yr–1 of Os is of cosmic derivation, corresponding to an accretion rate of extra-terrestrial Os to the Earth of 264 ± 21 mol yr–1.
Keywords	distillation ; hydrogen peroxide ; ice ; isotopes ; mass spectrometry ; nitric acid ; osmium ; snow ; snowmelt ; Greenland
Language	English
Dates of publication	2018-0408
Size	p. 5781-5787.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.8b00150
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Prenatal and postnatal mercury exposure and blood pressure in childhood

Shohreh F. Farzan / Caitlin G. Howe / Yu Chen / Diane Gilbert-Diamond / Susan Korrick / Brian P. Jackson / Adam R. Weinstein / Margaret R. Karagas

Environment International, Vol 146, Iss , Pp 106201- (2021)

2021

Abstract: Elevated blood pressure in childhood is an important risk factor for hypertension in adulthood. Environmental exposures have been associated with elevated blood pressure over the life course and exposure to mercury (Hg) has been linked to cardiovascular ... ...

Abstract	Elevated blood pressure in childhood is an important risk factor for hypertension in adulthood. Environmental exposures have been associated with elevated blood pressure over the life course and exposure to mercury (Hg) has been linked to cardiovascular effects in adults. As subclinical vascular changes begin early in life, Hg may play a role in altered blood pressure in children. However, the evidence linking early life Hg exposure to altered blood pressure in childhood has been largely inconsistent. In the ongoing New Hampshire Birth Cohort Study, we investigated prenatal and childhood Hg exposure at multiple time points and associations with blood pressure measurements in 395 young children (mean age 5.5 years, SD 0.4). Hg exposure was measured in children’s toenail clippings at age 3 and in urine at age 5–6 years, as well as in maternal toenail samples collected at ∼28 weeks gestation and 6 weeks postpartum, the latter two samples reflecting early prenatal and mid-gestation exposures, respectively. Five measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were averaged for each child using a standardized technique. In covariate-adjusted linear regression analyses, we observed that a 0.1 μg/g increase in child toenail Hg at age 3 or a 0.1 μg/L urine Hg at age 5–6 were individually associated with greater DBP (toenail β: 0.53 mmHg; 95% CI: −0.02, 1.07; urine β: 0.48 mmHg; 95% CI: 0.10, 0.86) and MAP (toenail β: 0.67 mmHg; 95% CI: 0.002, 1.33; urine β: 0.55 mmHg; 95% CI: 0.10, 1.01). Neither early prenatal nor mid-gestation Hg exposure, as measured by maternal toenails, were related to any changes to child BP. Simultaneous inclusion of both child urine Hg and child toenail Hg in models suggested a potentially stronger relationship of urine Hg at age 5–6 with DBP and MAP, as compared to toenail Hg at age 3. Our findings suggest that Hg exposure during childhood is associated with alterations in BP. Childhood may be an important window of opportunity to ...
Keywords	Mercury ; Children’s health ; Blood pressure ; Cohort ; New Hampshire ; Environmental sciences ; GE1-350
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Placental metal concentrations in relation to placental growth, efficiency and birth weight

Tracy Punshon / Zhigang Li / Brian P. Jackson / W. Tony Parks / Megan Romano / David Conway / Emily R. Baker / Margaret R. Karagas

Environment International, Vol 126, Iss , Pp 533-

2019 Volume 542

Abstract: The quality of the intrauterine environment, in which the placenta plays a critical role, affects birth outcomes and lifelong health. The effect of metal contaminants on the growth and functioning of the placenta have not been widely reported but may ... ...

Abstract	The quality of the intrauterine environment, in which the placenta plays a critical role, affects birth outcomes and lifelong health. The effect of metal contaminants on the growth and functioning of the placenta have not been widely reported but may provide insights into how metal exposures lead to these outcomes. We examined relationships between placental concentrations of cadmium (Cd), arsenic (As), mercury (Hg) and lead (Pb) and measures of placental growth and functioning (placental weight, placental efficiency (the log ratio of placental weight and birth weight), chorionic disc area and disc eccentricity) as part of the New Hampshire Birth Cohort Study (N = 1159). We additionally examined whether these associations were modified by placental concentrations of essential elements zinc (Zn) and selenium (Se). Associations were evaluated using generalized linear models. Multivariable-adjusted differences in placental weight were − 7.81 g (95% CI: −15.42, −2.48) with every ng/g increase in the Cd concentration of placenta (p-Value = 0.0009). Greater decrements in placental weight and efficiency associated with placental Cd were observed for females. For placentae with below median Zn and Se concentrations, decrements in placental weight were − 8.81 g (95% CI: −16.85, −0.76) and − 13.20 g (95% CI: −20.70, −5.70) respectively. The Cd concentration of placenta was also associated with reductions in placental efficiency both overall, and in Zn- and Se-stratified models. No appreciable differences were observed with other elements (As, Hg or Pb) and with other placental measures (chorionic disc area and disc eccentricity). In structural equation models, placental weight was a mediator in the relation between placental Cd concentration and reduced birth weight. Our findings suggest a role of interacting essential and contaminant elements on birth weight that may be mediated by changes in the growth and function of the placenta. Keywords: Placenta, Weight, Efficiency, Arsenic, Cadmium, Zinc, Selenium
Keywords	Environmental sciences ; GE1-350
Subject code	610
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns

Fu-Ying Tian / Todd M. Everson / Barry Lester / Tracy Punshon / Brian P. Jackson / Ke Hao / Corina Lesseur / Jia Chen / Margaret R. Karagas / Carmen J. Marsit

Environment International, Vol 137, Iss , Pp - (2020)

An epigenome-wide study of two U.S. birth cohorts

2020

Abstract: Background/Aim: Selenium (Se) levels in pregnancy have been linked to neurobehavioral development of the offspring. DNA methylation is a potential mechanism underlying the impacts of environmental exposures on fetal development; however, very few studies ...

Abstract	Background/Aim: Selenium (Se) levels in pregnancy have been linked to neurobehavioral development of the offspring. DNA methylation is a potential mechanism underlying the impacts of environmental exposures on fetal development; however, very few studies have been done elucidating the role of DNA methylation linking prenatal Se and child neurobehavior. We aimed to investigate the associations between placental Se concentration and epigenome-wide DNA methylation in two U.S. cohorts, and to assess the association between Se-related DNA methylation modifications and newborns’ neurobehavior. Methods: We measured placental Se concentrations in 343 newborns enrolled in the New Hampshire Birth Cohort Study and in 141 newborns in the Rhode Island Child Health Study. Genome-wide placental DNA methylation was measured by HumanMethylation450 BeadChip, and newborn neurobehavioral development was assessed by the NICU Network Neurobehavioral Scales (NNNS). We meta-analyzed the associations between placental Se concentration and DNA methylation in each cohort, adjusting for covariates. We also fit multiple linear regression and ordinal logistic regression for methylation and newborn NNNS summary scores. Results: We identified five Se-related differentially methylated CpG sites. Among them was cg09674502 (GFI1), where selenium concentration was positively associated with methylation (β-coefficient = 1.11, FDR-adjusted p-value = 0.045), and where we observed that a one percent methylation level increase was associated with a 15% reduced odds of higher muscle tone in the arms, legs and trunk of newborns, (OR [95% Confidence Interval, CI] = 0.85 [0.77, 0.95]). We also observed for each interquartile range (IQR) increase in selenium concentration in the placenta, there was 1.76 times greater odds of higher hypotonicity (OR [95% CI] = 1.76 [1.12, 2.82]). Conclusions: Placental selenium concentration was inversely associated with muscle tone of newborns, and hypermethylation of GFI1 could be a potential mechanism underlying this ...
Keywords	Environmental sciences ; GE1-350
Subject code	310
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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