Deciduous teeth from the New Hampshire birth cohort study: Early life environmental and dietary predictors of dentin elements.

BACKGROUND: Sparse research exists on predictors of element concentrations measured in deciduous teeth. OBJECTIVE: To estimate associations between maternal/child characteristics, elements measured in home tap water during pregnancy and element concentrations in the dentin of shed deciduous teeth. METHODS: Our analysis included 152 pregnant person-infant dyads followed from the second trimester through the end of the first postnatal year from the New Hampshire Birth Cohort Study. During pregnancy and early infancy, we collected dietary and sociodemographic information via surveys, measured elements in home tap water, and later collected naturally exfoliated teeth from child participants. We measured longitudinal deposition of elements in dentin using LA-ICP-MS. Multivariable linear mixed models were used to estimate associations between predictors and dentin element concentrations. RESULTS: We measured 12 elements in dentin including those previously reported (Ba, Mn, Pb, Sr, Zn) and less frequently reported (Al, As, Cd, Cu, Hg, Li, and W). A doubling of Pb or Sr concentrations in water was associated with higher dentin Pb or Sr respectively in prenatally formed [9% (95%CI: 3%, 15%); 3% (1%, 6%)] and postnatally formed [10% (2%, 19%); 6% (2%, 10%)] dentin. Formula feeding from birth to 6 weeks or 6 weeks to 4 months was associated with higher element concentrations in postnatal dentin within the given time period as compared to exclusive human milk feeding: Sr: 6 weeks: 61% (36%, 90%) and 4 months: 85% (54%, 121%); Ba: 6 weeks: 35% (3.3%, 77%) and 4 months: 42% (10%, 83%); and Li: 6 weeks: 61% (33%, 95%) and 4 months: 58% (31%, 90%). SIGNIFICANCE: These findings offer insights into predictors of dentin elements and potential confounders in exposure-health outcome relationships during critical developmental periods.

A new mRNA structure prediction based approach to identifying improved signal peptides for bone morphogenetic protein 2.

BACKGROUND: Signal peptide (SP) engineering has proven able to improve production of many proteins yet is a laborious process that still relies on trial and error. mRNA structure around the translational start site is important in translation initiation and has rarely been considered in this context, with recent improvements in in silico mRNA structure potentially rendering it a useful predictive tool for SP selection. Here we attempt to create a method to systematically screen candidate signal peptide sequences in silico based on both their nucleotide and amino acid sequences. Several recently released computational tools were used to predict signal peptide activity (SignalP), localization target (DeepLoc) and predicted mRNA structure (MXFold2). The method was tested with Bone Morphogenetic Protein 2 (BMP2), an osteogenic growth factor used clinically for bone regeneration. It was hoped more effective BMP2 SPs could improve BMP2-based gene therapies and reduce the cost of recombinant BMP2 production. RESULTS: Amino acid sequence analysis indicated 2,611 SPs from the TGF-ß superfamily were predicted to function when attached to BMP2. mRNA structure prediction indicated structures at the translational start site were likely highly variable. The five sequences with the most accessible translational start sites, a codon optimized BMP2 SP variant and the well-established hIL2 SP sequence were taken forward to in vitro testing. The top five candidates showed non-significant improvements in BMP2 secretion in HEK293T cells. All showed reductions in secretion versus the native sequence in C2C12 cells, with several showing large and significant decreases. None of the tested sequences were able to increase alkaline phosphatase activity above background in C2C12s. The codon optimized control sequence and hIL2 SP showed reasonable activity in HEK293T but very poor activity in C2C12. CONCLUSIONS: These results support the use of peptide sequence based in silico tools for basic predictions around signal peptide activity in a synthetic biology context. However, mRNA structure prediction requires improvement before it can produce reliable predictions for this application. The poor activity of the codon optimized BMP2 SP variant in C2C12 emphasizes the importance of codon choice, mRNA structure, and cellular context for SP activity.

Fish intake and mercury exposure in young children.

Fish consumption is one of the main sources of mercury (Hg) exposure, but few studies have examined Hg exposure from fish consumption among children. This study aimed to assess the frequency of fish intake and associations with Hg and other element concentrations among 700 three-year-old children from the New Hampshire Birth Cohort Study. Usual fish intake was derived from a validated food frequency questionnaire (Block Questionnaire for ages 2-7) and toenail element concentrations were determined using ICP-MS. Multiple linear regression analysis was used to assess the association between fish intake and toenail element concentrations. A mixture analysis, using Weighted quantile sum (WQS) regression, was used to estimate the relative contribution of fish consumption to element exposures. Twenty-three percent of children were reported to consume at least one fish meal/week on average during the previous 6 months. In adjusted linear regression models, children with any type of fish consumption versus no consumption had 108% (95% confidence interval (CI: 68%, 153%)) higher toenail Hg concentrations. To a lesser extent, children consuming "other fish (not fried) including tuna" and "fried fish or fish sticks" had 120% (95% CI: 82%, 164%), and 23% (95% CI: 2%, 51%) higher toenail concentrations, respectively, than those consuming no fish. Using WQS regression, Hg was the element most strongly related to fish consumption. Fish intake among young children was related to Hg exposure even at low levels of consumption. Future studies will need to determine the health consequences of this exposure.

Associations of Perinatal Metal and Metalloid Exposures with Early Child Behavioral Development Over Time in the New Hampshire Birth Cohort Study.

Research on the neurodevelopmental effects of metal(loid)s has focused mainly on outcomes assessed at one time point, even though brain development progresses over time. We investigated biomarkers of perinatal exposure to metals and changes in child behavior over time. We followed 268 participants from the prospective New Hampshire Birth Cohort Study between birth and age 5 years. We measured arsenic (As), copper (Cu), manganese (Mn), lead (Pb), selenium (Se), and zinc (Zn) in toenails from 6-week-old infants. The Behavioral Symptoms Index (BSI), externalizing, and internalizing symptoms were assessed using the Behavior Assessment System for Children, 2nd edition (BASC-2) at ages 3 and 5 years. Multivariable linear regression was used to estimate associations of metals with behavior change, calculated as the difference in symptom raw scores between 3 and 5 years, in addition to the associations for symptom scores at 3 and 5 years separately. Sex-specific associations were also explored using stratified models and a sex-metal interaction term. Adjusted associations of metals and change in behavior varied by exposure and outcome. Each 1 µg/g increase in ln toenail Cu was associated with improved behavior between 3 and 5 years [BSI: ß = - 3.88 (95%CI: - 7.12, - 0.64); Externalizing problems: ß = - 2.20 (95%CI: - 4.07, - 0.33)]. Increasing Zn was associated with increased externalizing behavior over time (ß = 3.42 (95%CI: 0.60, 6.25). Sex-stratified analyses suggested more pronounced associations among boys compared to girls. Perinatal exposure to metals may alter behavioral development between ages 3 and 5 years. Findings support the need for more research on associations between metals and neurodevelopment over longer time periods.

Integrative Co-Registration of Elemental Imaging and Histopathology for Enhanced Spatial Multimodal Analysis of Tissue Sections through TRACE.

Summary: Elemental imaging provides detailed profiling of metal bioaccumulation, offering more precision than bulk analysis by targeting specific tissue areas. However, accurately identifying comparable tissue regions from elemental maps is challenging, requiring the integration of hematoxylin and eosin (H&E) slides for effective comparison. Facilitating the streamlined co-registration of Whole Slide Images (WSI) and elemental maps, TRACE enhances the analysis of tissue regions and elemental abundance in various pathological conditions. Through an interactive containerized web application, TRACE features real-time annotation editing, advanced statistical tools, and data export, supporting comprehensive spatial analysis. Notably, it allows for comparison of elemental abundances across annotated tissue structures and enables integration with other spatial data types through WSI co-registration. Availability and Implementation: Available on the following platforms- GitHub: jlevy44/trace_app , PyPI: trace_app , Docker: joshualevy44/trace_app , Singularity: joshualevy44/trace_app . Contact: joshua.levy@cshs.org. Supplementary information: Supplementary data are available.

Lead exposure across the life course and age at death.

BACKGROUND: Lead (Pb) exposure has been associated with an increased risk of all-cause mortality, even at low levels. Little is known about how the timing of Pb exposure throughout life may influence these relationships. Quantifying the amount of Pb present in various tissues of the body provides measurements of exposure from different periods of life. These include bone, tooth enamel, which is the hard outer layer of the crown, and tooth cementum, which is the calcified connective tissue covering the tooth root. The purpose of the study was to examine Pb exposure at multiple periods throughout life, including childhood (enamel), adulthood (cementum), and later life (bone), and to estimate their associations with age at death. METHODS: 208 skeleton donors (born 1910-1960) from an ongoing case-control study were included in this study. Pb was measured in tibia (shin), bone using X-Ray Florescence and in teeth using Laser-Ablation Inductively Coupled Plasma Mass Spectroscopy. After excluding unusually high measurements (>2sd), this resulted in a final sample of 111 with all exposure measures. Correlations across measures were determined using partial Spearman correlations. Associations between Pb exposure and age at death were estimated using Multivariable Linear Regression. RESULTS: Pb measures across exposure periods were all significantly correlated, with the highest correlation between cementum and tibia measures (r = 0.61). Donors were largely female (63.0 %), White (97.3 %), and attended some college (49.5 %). Single exposure models found that higher tooth cementum Pb (-1.27; 95 % CI: -2.48, -0.06) and tibia bone Pb (-0.91; 95 % CI: -1.67, -0.15) were significantly associated with an earlier age at death. When considered simultaneously, only cementum Pb remained significant (-1.51; 95 % CI: -2.92, -0.11). Secondary analyses suggest that the outer cementum Pb may be especially associated with an earlier age at death. CONCLUSION: Results suggest that higher Pb exposure is associated with an earlier age at death, with adulthood as the life period of most relevance. Additional studies using Pb exposure measures from different life stages should be conducted.

Seasonal patterns in trace elements assessed in toenails.

BACKGROUND: Seasonal patterns in measured exposure biomarkers can cause measurement error in epidemiological studies. There is little research about the seasonality of metals and trace elements when assessed in toenail samples. Adjusting for such patterns in models for estimating associations between long-term exposures and health outcomes can potentially improve precision and reduce bias. OBJECTIVES: Assess and describe seasonal patterns in toenail measurements of trace elements. METHODS: The Sister Study enrolled women residing in the US, including Puerto Rico, whose sister had been diagnosed with breast cancer. At the time of enrollment, participants removed nail polish and collected their toenail clippings, which were cleaned before analysis. We considered the following elements: iron, vanadium, aluminum, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, molybdenum, cadmium, tin, antimony, mercury, and lead. For two subsamples of the cohort, we fit trigonometric regression models with toenail element measures as the outcome, using sine and cosine functions of the collection day (transformed to an angle) to capture seasonal patterns. These models can estimate the amplitude and timing of the peaks in measures. We evaluated the evidence for a seasonal effect by comparing for each measured element the trigonometric model to a model that was constant across time. RESULTS: There was a seasonal trend in toenail element concentration for iron, aluminum, vanadium, chromium, manganese, cobalt, arsenic, molybdenum, cadmium, tin, and lead, all of which peaked near mid-August. Seasonal patterns were concordant across two non-overlapping samples of women, analyzed in different labs. DISCUSSION: Given the evidence supporting seasonal patterns for 11 of the 17 elements measured in toenails, correcting for seasonality of toenail levels of those trace elements in models estimating the association between those exposures and health outcomes is important. The basis for higher concentrations in toenails collected during the summer remains unknown.

Quantified retrospective biomonitoring of fetal and infant elemental exposure using LA-ICP-MS analysis of deciduous dentin in three contrasting human cohorts.

BACKGROUND: Spatial elemental analysis of deciduous tooth dentin combined with odontochronological estimates can provide an early life (in utero to ~2 years of age) history of inorganic element exposure and status. OBJECTIVE: To demonstrate the importance of data normalization to a certified reference material to enable between-study comparisons, using populations with assumed contrasting elemental exposures. METHODS: We used laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) of dentin to derive a history of elemental composition from three distinct cohort studies: a present day rural cohort, (the New Hampshire Birth Cohort Study (NHBCS; N = 154)), an historical cohort from an urban area (1958-1970), (the St. Louis Baby Tooth Study (SLBT; N = 78)), and a present-day Nigerian cohort established to study maternal HIV transmission (Dental caries and its association with Oral Microbiomes and HIV in young children-Nigeria (DOMHaIN; N = 31)). RESULTS: We report Li, Al, Mn, Cu, Zn, Sr, Ba and Pb concentrations (µg/g) and qualitatively examine As, Cd and Hg across all three cohorts. Rates of detection were highest, both overall and for each cohort individually, for Zn, Sr, Ba and Li. Zinc was detected in 100% of samples and was stably present in teeth at a concentration range of 64 - 86 µg/g. Mercury, As and Cd detection rates were the lowest, and had high variability within individual ablated spots. We found the highest concentrations of Pb in the pre- and postnatal dentin of the SLBT cohort, consistent with the prevalent use of Pb as an additive to gasoline prior to 1975. The characteristic decline in Mn after the second trimester was observed in all cohorts. IMPACT: Spatially resolved elemental analysis of deciduous teeth combined with methods for estimating crown formation times can be used to reconstruct an early-life history of elemental exposure inaccessible via other biomarkers. Quantification of data into absolute values using an external standard reference material has not been conducted since 2012, preventing comparison between studies, a common and highly informative component of epidemiology. We demonstrate, with three contrasting populations, that absolute quantification produces data with the lowest variability, compares well with available data and recommends that future tooth biomarker studies report data in this way.

Urinary biomarkers of exposure to toxic and essential elements: A comparison of infants fed with human milk or formula.

Background: Early-life exposure to nonessential (toxic) and essential trace elements can influence child development. Although infant formula powders and the water used to reconstitute them can contain higher concentrations of many elements compared with human milk, the influence of feeding mode on reliable biomarkers of infant exposure has rarely been demonstrated. Methods: We evaluated associations between urinary biomarkers and feeding mode (exclusively human milk, exclusively formula, or combination-fed) for four toxic (arsenic, cadmium, nickel, and uranium) and three essential elements (cobalt, molybdenum, and selenium) using general linear models. Results: A total of 462 participants from the rural New Hampshire Birth Cohort Study were on average 6 weeks old between July 2012 and March 2019 and had urine samples, 3-day food diaries, and relevant covariate data available. In adjusted models, urinary arsenic was 5.15 (95% confidence interval = 4.04, 6.58), molybdenum was 19.02 (14.13-25.59), and selenium was 1.51 (1.35-1.68) times higher in infants fed exclusively with formula compared with infants fed exclusively with human milk. By contrast, urinary uranium was 0.59 (0.46-0.75) and cobalt was 0.78 (0.65-0.95) times lower with formula feeding than human milk feeding. Conclusion: Our findings suggest that infant exposure to several potentially toxic elements varies by feeding mode, as concentrations of reliable urinary biomarkers were higher with formula or human milk, depending on the element. Importantly, exposure to arsenic increased with household tap water arsenic regardless of feeding mode, suggesting that all infants could be at risk in populations with high concentrations of arsenic in drinking water.

Toenail and serum levels as biomarkers of iron status in pre- and postmenopausal women: correlations and stability over eight-year follow-up.

Iron status is often assessed in epidemiologic studies, and toenails offer a convenient alternative to serum because of ease of collection, transport, and storage, and the potential to reflect a longer exposure window. Very few studies have examined the correlation between serum and toenail levels for trace metals. Our aim was to compare iron measures using serum and toenails on both a cross-sectional and longitudinal basis. Using a subset of the US-wide prospective Sister Study cohort, we compared toenail iron measures to serum concentrations for iron, ferritin and percent transferrin saturation. Among 146 women who donated both blood and toenails at baseline, a subsample (59%, n = 86) provided specimens about 8 years later. Cross-sectional analyses included nonparametric Spearman's rank correlations between toenail and serum biomarker levels. We assessed within-woman maintenance of rank across time for the toenail and serum measures and fit mixed effects models to measure change across time in relation to change in menopause status. Spearman correlations at baseline (follow-up) were 0.08 (0.09) for serum iron, 0.08 (0.07) for transferrin saturation, and - 0.09 (- 0.17) for ferritin. The within-woman Spearman correlation for toenail iron between the two time points was higher (0.47, 95% CI 0.30, 0.64) than for serum iron (0.30, 95% CI 0.09, 0.51) and transferrin saturation (0.34, 95% CI 0.15, 0.54), but lower than that for ferritin (0.58, 95% CI 0.43, 0.73). Serum ferritin increased over time while nail iron decreased over time for women who experienced menopause during the 8-years interval. Based on cross-sectional and repeated assessments, our evidence does not support an association between serum biomarkers and toenail iron levels. Toenail iron concentrations did appear to be moderately stable over time but cannot be taken as a proxy for serum iron biomarkers and they may reflect physiologically distinct fates for iron.

The contributions of neonatal inhalation of copper to air pollution-induced neurodevelopmental outcomes in mice.

Exposures to ambient ultrafine particle (UFP) air pollution (AP) during the early postnatal period in mice (equivalent to human third trimester brain development) produce male-biased changes in brain structure, including ventriculomegaly, reduced brain myelination, alterations in neurotransmitters and glial activation, as well as impulsive-like behavioral characteristics, all of which are also features characteristic of male-biased neurodevelopmental disorders (NDDs). The purpose of this study was to ascertain the extent to which inhaled Cu, a common contaminant of AP that is also dysregulated across multiple NDDs, might contribute to these phenotypes. For this purpose, C57BL/6J mice were exposed from postnatal days 4-7 and 10-13 for 4 hr/day to inhaled copper oxide (CuxOy) nanoparticles at an environmentally relevant concentration averaging 171.9 ng/m3. Changes in brain metal homeostasis and neurotransmitter levels were determined following termination of exposure (postnatal day 14), while behavioral changes were assessed in adulthood. CuxOy inhalation modified cortical metal homeostasis and produced male-biased disruption of striatal neurotransmitters, with marked increases in dopaminergic function, as well as excitatory/inhibitory imbalance and reductions in serotonergic function. Impulsive-like behaviors in a fixed ratio (FR) waiting-for-reward schedule and a fixed interval (FI) schedule of food reward occurred in both sexes, but more prominently in males, effects which could not be attributed to altered locomotor activity or short-term memory. Inhaled Cu as from AP exposures, at environmentally relevant levels experienced during development, may contribute to impaired brain function, as shown by its ability to disrupt brain metal homeostasis and striatal neurotransmission. In addition, its ability to evoke impulsive-like behavior, particularly in male offspring, may be related to striatal dopaminergic dysfunction that is known to mediate such behaviors. As such, regulation of air Cu levels may be protective of public health.

Periconceptional and Prenatal Exposure to Metals and Extracellular Vesicle and Particle miRNAs in Human Milk: A Pilot Study.

Human milk is a rich source of microRNAs (miRNAs), which can be transported by extracellular vesicles and particles (EVPs) and are hypothesized to contribute to maternal-offspring communication and child development. Environmental contaminant impacts on EVP miRNAs in human milk are largely unknown. In a pilot study of 54 mother-child pairs from the New Hampshire Birth Cohort Study, we examined relationships between five metals (arsenic, lead, manganese, mercury, and selenium) measured in maternal toenail clippings, reflecting exposures during the periconceptional and prenatal periods, and EVP miRNA levels in human milk. 798 miRNAs were profiled using the NanoString nCounter platform; 200 miRNAs were widely detectable and retained for downstream analyses. Metal-miRNA associations were evaluated using covariate-adjusted robust linear regression models. Arsenic exposure during the periconceptional and prenatal periods was associated with lower total miRNA content in human milk EVPs (PBonferroni < 0.05). When evaluating miRNAs individually, 13 miRNAs were inversely associated with arsenic exposure, two in the periconceptional period and 11 in the prenatal period (PBonferroni < 0.05). Other metal-miRNA associations were not statistically significant after multiple testing correction (PBonferroni ≥ 0.05). Many of the arsenic-associated miRNAs are involved in lactation and have anti-inflammatory properties in the intestine and tumor suppressive functions in breast cells. Our findings raise the possibility that periconceptional and prenatal arsenic exposure may reduce levels of multiple miRNAs in human milk EVPs. However, larger confirmatory studies, which can apply environmental mixture approaches, evaluate potential effect modifiers of these relationships, and examine possible downstream consequences for maternal and child health and breastfeeding outcomes, are needed.

Oxidation of hemoglobin in the lung parenchyma facilitates the differentiation of pneumococci into encapsulated bacteria.

Pneumococcal pneumonia causes cytotoxicity in the lung parenchyma but the underlying mechanism involves multiple factors contributing to cell death. Here, we discovered that hydrogen peroxide produced by Streptococcus pneumoniae (Spn-H 2 O 2 ) plays a pivotal role by oxidizing hemoglobin, leading to its polymerization and subsequent release of labile heme. At physiologically relevant levels, heme selected a population of encapsulated pneumococci. In the absence of capsule and Spn-H 2 O 2 , host intracellular heme exhibited toxicity towards pneumococci, thus acting as an antibacterial mechanism. Further investigation revealed that heme-mediated toxicity required the ABC transporter GlnPQ. In vivo experiments demonstrated that pneumococci release H 2 O 2 to cause cytotoxicity in bronchi and alveoli through the non-proteolytic degradation of intracellular proteins such as actin, tubulin and GAPDH. Overall, our findings uncover a mechanism of lung toxicity mediated by oxidative stress that favor the growth of encapsulated pneumococci suggesting a therapeutic potential by targeting oxidative reactions. Highlights: Oxidation of hemoglobin by Streptococcus pneumoniae facilitates differentiation to encapsulated pneumococci in vivo Differentiated S. pneumoniae produces capsule and hydrogen peroxide (Spn-H 2 O 2 ) as defense mechanism against host heme-mediated toxicity. Spn-H 2 O 2 -induced lung toxicity causes the oxidation and non-proteolytic degradation of intracellular proteins tubulin, actin, and GAPDH. The ABC transporter GlnPQ is a heme-binding complex that makes Spn susceptible to heme toxicity.

Gadolinium-based Contrast Agent Biodistribution and Speciation in Rats.

Background Gadolinium retention has been observed in organs of patients with normal renal function; however, the biodistribution and speciation of residual gadolinium is not well understood. Purpose To compare the pharmacokinetics, distribution, and speciation of four gadolinium-based contrast agents (GBCAs) in healthy rats using MRI, mass spectrometry, elemental imaging, and electron paramagnetic resonance (EPR) spectroscopy. Materials and Methods In this prospective animal study performed between November 2021 and September 2022, 32 rats received a dose of gadoterate, gadoteridol, gadobutrol, or gadobenate (2.0 mmol/kg) for 10 consecutive days. GBCA-naive rats were used as controls. Three-dimensional T1-weighted ultrashort echo time images and R2* maps of the kidneys were acquired at 3, 17, 34, and 52 days after injection. At 17 and 52 days after injection, gadolinium concentrations in 23 organ, tissue, and fluid specimens were measured with mass spectrometry; gadolinium distribution in the kidneys was evaluated using elemental imaging; and gadolinium speciation in the kidney cortex was assessed using EPR spectroscopy. Data were assessed with analysis of variance, Kruskal-Wallis test, analysis of response profiles, and Pearson correlation analysis. Results For all GBCAs, the kidney cortex exhibited higher gadolinium retention at 17 days after injection than all other specimens tested (mean range, 350-1720 nmol/g vs 0.40-401 nmol/g; P value range, .001-.70), with gadoteridol showing the lowest level of retention. Renal cortex R2* values correlated with gadolinium concentrations measured ex vivo (r = 0.95; P < .001), whereas no associations were found between T1-weighted signal intensity and ex vivo gadolinium concentration (r = 0.38; P = .10). EPR spectroscopy analysis of rat kidney cortex samples showed that all GBCAs were primarily intact at 52 days after injection. Conclusion Compared with other macrocyclic GBCAs, gadoteridol administration led to the lowest level of retention. The highest concentration of gadolinium was retained in the kidney cortex, but T1-weighted MRI was not sensitive for detecting residual gadolinium in this tissue. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Tweedle in this issue.

Prenatal exposure to metal mixtures and lung function in children from the New Hampshire birth cohort study.

Prenatal exposure to metals/metalloids, even at common US population levels, may pose risks to fetal health, and affect children's lung function. Yet, the combined effects of simultaneous prenatal exposures on children's lung function remain largely unexplored. This study analyzed 11 metals (As speciation, Cd, Co, Cu, Mo, Ni, Pb, Sb, Se, Sn, Zn) in maternal urine during weeks 24-28 of gestation and evaluated lung function, including forced vital capacity (FVC) and forced expiratory volume in the first second of expiration (FEV1), in 316 US mother-child pairs at around age 7. We used Bayesian Kernel Machine Regression (BKMR), weighted quantile sum regression (WQSR), and multiple linear regression to examine the association between metal mixture exposure and children's lung function, adjusting for maternal smoking, child age, sex, and height. In BKMR models assessing combined exposure effects, limited evidence of metal non-linearity or interactions was found. Nevertheless, Co, As species, and Pb showed a negative association, while Mo exhibited a positive association with children's FVC and FEV1, with other metals held constant at their medians. The weighted index, from WQSR analysis assessing the cumulative impact of all metals, highlighted prenatal Mo with the highest positive weight, and Co, As, and Sb with the most substantial negative weights on children's FVC and FEV1. Urinary Co and Pb were negatively associated with FVC (ß = -0.09, 95% confidence interval (CI) (-0.18; -0.01) and ß = -0.07, 95% CI (-0.13; 0.00), respectively). Co was also negatively associated with FEV1 (ß = -0.09, 95% CI (-0.18; 0.00). There was a negative association between As and FVC, and a positive association between Mo and both FVC and FEV1, though with wide confidence intervals. Our findings suggest that prenatal trace element exposures may impact children's lung function, emphasizing the importance of reducing toxic exposures and maintaining adequate nutrient levels.

Evidence of elevated heavy metals concentrations in wild and farmed sugar kelp (Saccharina latissima) in New England.

Seaweed farming in the United States is gaining significant financial and political support due to prospects to sustainably expand domestic economies with environmentally friendly products. Several networks are seeking appropriate synthesis of available science to both inform policy and substantiate the sector's sustainability claims. Significant knowledge gaps remain regarding seaweed-specific food hazards and their mitigation; a resource-intensive challenge that can inhibit sustainable policies. This is particularly concerning for rapidly expanding Saccharina latissima (sugar kelp) crops, a brown seaweed that is known to accumulate heavy metals linked to food hazards. Here, we present baseline information about concentrations of arsenic, cadmium, lead, and mercury, in both wild and farmed sugar kelp from the New England region. We interpret our findings based on proximity to potential sources of contamination, location on blade, and available heavy metals standards. Contrary to our expectations, high concentrations were widespread in both wild and farmed populations, regardless of proximity to contamination. We find, like others, that cadmium and arsenic consistently reach levels of regulatory concern, and that dried seaweeds could harbor higher concentrations compared to raw products. We also share unique findings that suggest some toxins concentrate at the base of kelp blades. Our results are one step towards aggregating vital data for the region to expand its seaweed farming footprint.

Bacterial Modification of the Association Between Arsenic and Autism-Related Social Behavior Scores.

Arsenic is related to neurodevelopmental outcomes and is associated with the composition of the gut microbiome. Data on the modifying role of the microbiome are limited. We probed suggestive relationships between arsenic and social behaviors to quantify the modifying role of the infant gut microbiome. We followed children for whom arsenic concentrations were quantified in 6-week-old toenail clippings. Scores on the Social Responsiveness Scale (SRS-2), which measures autism-related social behaviors, were provided by caregivers when the child was approximately 3 years of age. Metagenomic sequencing was performed on infant stools collected at 6 weeks and 1 year of age. To evaluate modification by the top ten most abundant species and functional pathways, we modeled SRS-2 total T-scores as a function of arsenic concentrations, microbiome features dichotomized at their median, and an interaction between exposure and the microbiome, adjusting for other trace elements and sociodemographic characteristics. As compared to the standardized population (SRS-2 T-scores = 50), participants in our study had lower SRS-2 scores (n = 78, mean = 44, SD = 5).The relative abundances of several functional pathways identified in 6-week stool samples modified the arsenic-SRS-2 association, including the pathways of valine and isoleucine biosynthesis; we observed no association among those with high relative abundance of each pathway [ß = - 0.67 (95% CI - 1.46, 0.12)], and an adverse association [ß = 1.67 (95% CI 0.3, 3.04), pinteraction= 0.05] among infants with low relative abundance. Our findings indicate the infant gut microbiome may alter neurodevelopmental susceptibility to environmental exposures.

Improving the Customer Experience: Physician Feedback Program for Clinical Laboratories.

CONTEXT.­: Clinician feedback is an important source of information for laboratory quality improvement programs. OBJECTIVE.­: To pilot a program for nearly real-time solicitation and analysis of physician feedback regarding clinical laboratory services. DESIGN.­: Laboratories distributed either electronic or paper survey forms to physicians. Results were tabulated by College of American Pathologists staff. Free-text comments were shared promptly with the participating laboratories to facilitate follow-up. RESULTS.­: Forty-seven clinical laboratories participated in the study and submitted results for 987 physician surveys, including both paper and electronic forms. Of 694 responses submitted electronically within the study period, 460 (66.3%) included at least 1 free-text entry, for a total of 951 free-text comments. CONCLUSIONS.­: Point-of-service solicitation of physician feedback regarding clinical laboratory services is feasible and can provide a substantial quantity of potentially useful information regarding laboratory performance from the customer perspective.