Background:Previous studies suggest that blood lead levels are positively associated with attention deficit/hyperactivity disorder (ADHD) and ADHD-symptoms in children. However, the associations between lead exposure and ADHD subtypes are inconsistent and understudied.Objective:The objective of this study was to explore the association of low-level concurrent lead exposure with subtypes of ADHD symptoms in 578 Mexican children 6–13 years of age.Methods:We measured concurrent blood lead levels using inductively coupled plasma mass spectrometry (ICPMS). We administered the Conners’ Rating Scales-Revised (CRS-R) to mothers to evaluate their children’s ADHD symptoms. We used imputation to fill missing values in blood lead levels and used segmented regression models adjusted for relevant covariates to model the nonlinear relationship between blood lead and ADHD symptoms.Results:Mean ± SD blood lead levels were 3.4 ± 2.9 μg/dL. In adjusted models, a 1-μg/dL increase in blood lead was positively associated with Hyperactivity and Restless-Impulsivity scores on the CRS-R scale and Hyperactivity-Impulsivity scores on the CRS-R scale of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, but only in children with blood lead level ≤ 5 μg/dL. Blood lead was not associated with Inattentive symptoms or overall ADHD behavior.Conclusions:In this population of Mexican children, current blood lead level among children with low exposure (≤ 5 μg/dL) was positively associated with hyperactive/impulsive behaviors, but not with inattentiveness. These results add to the existing evidence of lead-associated neurodevelopmental deficits at low levels of exposure.Citation:Huang S, Hu H, Sánchez BN, Peterson KE, Ettinger AS, Lamadrid-Figueroa H, Schnaas L, Mercado-García A, Wright RO, Basu N, Cantonwine DE, Hernández-Avila M, Téllez-Rojo MM. 2016. Childhood blood lead levels and symptoms of attention deficit hyperactivity disorder (ADHD): a cross-sectional study of Mexican children. Environ Health Perspect 124:868–874; http://dx.doi.org/10.1289/ehp.1510067

Vegetable oil-based polymeric materials always suffer from relatively poor performance, such as lower tensile strength and glass transition temperatures, than petroleum-based polymeric materials, which greatly limit their practical applications. In this study, octahydro-2,5-pentalenediol (OPD) was synthesized from naturally occurring citric acid and used together with castor oil as the polyol blends for the production of bio-based waterborne polyurethane (PU) dispersions (PUDs). The effects of the OPD contents on the particle size and ζ potential of the resulting polyurethane dispersion, and the thermal stability, mechanical properties, and hydrophilicity of the resulting polyurethane films were systematically investigated. Taking advantage of the rigid cyclic structures of the OPD and the flexible fatty acid chain of castor oil, waterborne polyurethane (WPU) films with tailorable mechanical performance ranging from elastomeric polymers to rigid plastics were successfully prepared and characterized. The tensile strength of the samples increases from 9.5 to 22.3 MPa with the ratio between OPD and castor oil increasing from 0:10 to 5:5, whereas their elongation at break decreases from 192 to 12%. A significant increase in the glass transition temperature, transparency, and anticorrosive properties was observed for the resulting polyurethane films with increasing the OPD content. However, the thermal stability of the PU films exhibited a slight decrease as the OPD content increased. Moreover, the water contact angle exhibited a slight increase for the polyurethane films prepared from polyol blends compared to the WPU film prepared from pure castor oil. This work provides a novel route to tailor the performance of vegetable oil-based waterborne polyurethanes through the incorporation of rigid cyclic rings into soft polymer networks.

Caenorhabditis elegans is an instrumental research model used to advance our knowledge in areas including development, metabolism, and aging. However, research on metabolism and/or other measures of health/aging are confounded by the nematode’s food source in the lab, live E. coli bacteria. Commonly used treatments, including ultraviolet irradiation and antibiotics, are successful in preventing bacterial replication, but the bacteria can remain metabolically active. The purpose of this study is to develop a metabolically inactive food source for the worms that will allow us to minimize the confounding effects of bacterial metabolism on worm metabolism and aging. Our strategy is to use a paraformaldehyde (PFA) treated E. coli food source and to determine its effects on worm health, metabolism and longevity. We initially determine the lowest possible concentrations of PFA necessary to rapidly and reproducibly kill bacteria. We then measure various aspects of worm behavior, healthspan and longevity, including growth rate, food attraction, brood size, lifespan and metabolic assessments, such as oxygen consumption and metabolomics. Our resulting data show that worms eat and grow well on these bacteria and support the use of 0.5% PFA-killed bacteria as a nematode food source for metabolic, drug, and longevity experiments.

Efficient interventions to reduce blood triglycerides are few; newer and more tolerable intervention targets are needed. Understanding the molecular mechanisms underlying blood triglyceride levels variation is key to identifying new therapies. To explore the role of epigenetic mechanisms on triglyceride levels, a blood methylome scan was conducted in 199 individuals from 5 French-Canadian families ascertained on venous thromboembolism, and findings were replicated in 324 French unrelated patients with venous thromboembolism. Genetic context and functional relevance were investigated. Two DNA methylation sites associated with triglyceride levels were identified. The first one, located in the ABCG1 gene, was recently reported, whereas the second one, located in the promoter of the PHGDH gene, is novel. The PHGDH methylation site, cg14476101, was found to be associated with variation in triglyceride levels in a threshold manner: cg14476101 was inversely associated with triglyceride levels only when triglyceride levels were above 1.12 mmol/L (discovery P-value = 8.4 × 10−6; replication P-value = 0.0091). Public databases findings supported a functional role of cg14476101 on PHGDH expression. PHGDH catalyses the first step in the serine biosynthesis pathway. These findings highlight the role of epigenetic regulation of the PHGDH gene in triglyceride metabolism, providing novel insights on putative intervention targets.

An organism’s ability to perceive and respond to changes in its environment is crucial for its health and survival. Here we reveal how the most well-studied longevity intervention, dietary restriction, acts in-part through a cell non-autonomous signaling pathway that is inhibited by the presence of attractive smells. Using an intestinal reporter for a key gene induced by dietary restriction but suppressed by attractive smells, we identify three compounds that block food odor effects in C. elegans, thereby increasing longevity as dietary restriction mimetics. These compounds clearly implicate serotonin and dopamine in limiting lifespan in response to food odor. We further identify a chemosensory neuron that likely perceives food odor, an enteric neuron that signals through the serotonin receptor 5-HT1A/SER-4, and a dopaminergic neuron that signals through the dopamine receptor DRD2/DOP-3. Aspects of this pathway are conserved in D. melanogaster. Thus, blocking food odor signaling through antagonism of serotonin or dopamine receptors is a plausible approach to mimic the benefits of dietary restriction.

Flavin-Containing Monooxygenases are conserved xenobiotic-detoxifying enzymes. Recent studies have revealed endogenous functions of FMOs in regulating longevity in Caenorhabditis elegans and in regulating aspects of metabolism in mice. To explore the cellular mechanisms of FMO’s endogenous function, here we demonstrate that all five functional mammalian FMOs may play similar endogenous roles to improve resistance to a wide range of toxic stresses in both kidney and liver cells. We further find that stress-activated c-Jun N-terminal kinase activity is enhanced in FMO-overexpressing cells, which may lead to increased survival under stress. Furthermore, FMO expression modulates cellular metabolic activity as measured by mitochondrial respiration, glycolysis, and metabolomics analyses. FMO expression augments mitochondrial respiration and significantly changes central carbon metabolism, including amino acid and energy metabolism pathways. Together, our findings demonstrate an important endogenous role for the FMO family in regulation of cellular stress resistance and major cellular metabolic activities including central carbon metabolism.

Background: The grading and pathologic biomarkers of glioma has important guiding significance for the individual treatment. In clinical, it is often necessary to obtain tumor samples through invasive operation for pathological diagnosis. The present study aimed to use conventional machine learning algorithms to predict the tumor grades and pathologic biomarkers on magnetic resonance imaging (MRI) data. Methods: The present study retrospectively collected a dataset of 367 glioma patients, who had pathological reports and underwent MRI scans between October 2013 and March 2019. The radiomic features were extracted from enhanced MRI images, and three frequently-used machine-learning models of LC, Support Vector Machine (SVM), and Random Forests (RF) were built for four predictive tasks: (1) glioma grades, (2) Ki67 expression level, (3) GFAP expression level, and (4) S100 expression level in gliomas. Each sub dataset was split into training and testing sets at a ratio of 4:1. The training sets were used for training and tuning models. The testing sets were used for evaluating models. According to the area under curve (AUC) and accuracy, the best classifier was chosen for each task. Results: The RF algorithm was found to be stable and consistently performed better than Logistic Regression and SVM for all the tasks. The RF classifier on glioma grades achieved a predictive performance (AUC: 0.79, accuracy: 0.81). The RF classifier also achieved a predictive performance on the Ki67 expression (AUC: 0.85, accuracy: 0.80). The AUC and accuracy score for the GFAP classifier were 0.72 and 0.81. The AUC and accuracy score for S100 expression levels are 0.60 and 0.91. Conclusion: The machine-learning based radiomics approach can provide a noninvasive method for the prediction of glioma grades and expression levels of multiple pathologic biomarkers, preoperatively, with favorable predictive accuracy and stability.

Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans, fmo-2 expression increases lifespan and healthspan downstream of multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, beyond its classification as a xenobiotic enzyme, fmo-2 expression leads to rewiring of endogenous metabolism principally through changes in one carbon metabolism (OCM). These changes are likely relevant, as we find that genetically modifying OCM enzyme expression leads to alterations in longevity that interact with fmo-2 expression. Using computer modeling, we identify decreased methylation as the major OCM flux modified by FMO-2 that is sufficient to recapitulate its longevity benefits. We further find that tryptophan is decreased in multiple mammalian FMO overexpression models and is a validated substrate for FMO-2. Our resulting model connects a single enzyme to two previously unconnected key metabolic pathways and provides a framework for the metabolic interconnectivity of longevity-promoting pathways such as dietary restriction. FMOs are well-conserved enzymes that are also induced by lifespan-extending interventions in mice, supporting a conserved and important role in promoting health and longevity through metabolic remodeling.