Endocrine-disrupting effects of cattle feedlot effluent on an aquatic sentinel species, the fathead minnow.

Over the last decade, research has examined the endocrine-disrupting action of various environmental pollutants, including hormones, pharmaceuticals, and surfactants, in sewage treatment plant effluent. Responding to the growth of concentrated animal feeding operations (CAFOs) and the pollutants present in their wastewater (e.g., nutrients, pharmaceuticals, and hormones), the U.S. Environmental Protection Agency developed a new rule that tightens the regulation of CAFOs. In this study, we collected wild fathead minnows (Pimephales promelas) exposed to feedlot effluent (FLE) and observed significant alterations in their reproductive biology. Male fish were demasculinized (having lower testicular testosterone synthesis, altered head morphometrics, and smaller testis size). Defeminization of females, as evidenced by a decreased estrogen:androgen ratio of in vitro steroid hormone synthesis, was also documented. We did not observe characteristics in either male or female fish indicative of exposure to environmental estrogens. Using cells transfected with the human androgen receptor, we detected potent androgenic responses from the FLE. Taken together, our morphologic, endocrinologic, and in vitro gene activation assay data suggest two hypotheses: a) there are potent androgenic substance(s) in the FLE, and/or b) there is a complex mixture of androgenic and estrogenic substances that alter the hypothalamic-pituitary-gonadal axis, inhibiting the release of gonadotropin-releasing hormone or gonadotropins. This is the first study demonstrating that the endocrine and reproductive systems of wild fish can be adversely affected by FLE. Future studies are needed to further investigate the effects of agricultural runoff and to identify the biologically active agents, whether natural or pharmaceutical in origin

Neuro-environmental interactions: a time sensitive matter

Introduction: The assessment of resting state (rs) neurophysiological dynamics relies on the control of sensory, perceptual, and behavioral environments to minimize variability and rule-out confounding sources of activation during testing conditions. Here, we investigated how temporally-distal environmental inputs, specifically metal exposures experienced up to several months prior to scanning, affect functional dynamics measured using rs functional magnetic resonance imaging (rs-fMRI). Methods: We implemented an interpretable XGBoost-shapley additive explanation (SHAP) model that integrated information from multiple exposure biomarkers to predict rs dynamics in typically developing adolescents. In 124 participants (53% females, ages, 13-25 years) enrolled in the public health impact of metals exposure (PHIME) study, we measured concentrations of six metals (manganese, lead, chromium, copper, nickel, and zinc) in biological matrices (saliva, hair, fingernails, toenails, blood, and urine) and acquired rs-fMRI scans. Using graph theory metrics, we computed global efficiency (GE) in 111 brain areas (Harvard Oxford atlas). We used a predictive model based on ensemble gradient boosting to predict GE from metal biomarkers, adjusting for age and biological sex. Results: Model performance was evaluated by comparing predicted versus measured GE. SHAP scores were used to evaluate feature importance. Measured versus predicted rs dynamics from our model utilizing chemical exposures as inputs were significantly correlated (p < 0.001, r = 0.36). Lead, chromium, and copper contributed most to the prediction of GE metrics. Discussion: Our results indicate that a significant component of rs dynamics, comprising approximately 13% of observed variability in GE, is driven by recent metal exposures. These findings emphasize the need to estimate and control for the influence of past and current chemical exposures in the assessment and analysis of rs functional connectivity

Impact of COVID-19-Related Social Isolation on Behavioral Outcomes in Young Adults Residing in Northern Italy

: Social isolation affects our emotions, behavior and interactions. Worldwide, individuals experienced prolonged periods of isolation during the first wave of the COVID-19 pandemic when authorities-imposed restrictions to reduce the spread of the virus. In this study, we investigated the effects of social isolation on emotional and behavioral outcomes in young adults from Lombardy, Italy, a global hotspot of COVID-19. We leveraged baseline (pre-social isolation) and follow-up (mid- or post-isolation) data collected from young adults enrolled in the ongoing, longitudinal Public Health Impact of Metals Exposure (PHIME) study. At baseline, 167 participants completed the ASEBA questionnaires (ASR/YSR) by web link or in person; 65 completed the ASR 12-18 weeks after the onset of restrictions. Using the sign test and multiple linear regression models, we examined differences in ASR scores between baseline and follow-up adjusting for sex, age, pre-pandemic IQ and time with social restrictions (weeks). Further, we examined interactions between sex and time in social isolation. Participants completed the ASR after spending an average of 14 weeks in social isolation (range 12-18 weeks). Thought problems increased between baseline and follow-up (median difference 1.0; 1st, 3rd quartile: -1.0, 4.0; p = 0.049). Among males, a longer time in social isolation (≥14 weeks) was associated with increased rule-breaking behaviors of 2.8 points. These results suggest the social isolation related to COVID-19 adversely impacted mental health. In particular, males seem to externalize their condition. These findings might help future interventions and treatment to minimize the consequences of social isolation experience in young adults

Predictors of serum concentrations of polybrominated flame retardants among healthy pregnant women in an urban environment: a cross-sectional study

Background: Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants commonly used in a wide range of products. Prenatal exposure to PBDEs has been associated with adverse neurodevelopment. Our objective was to characterize predictors of exposure to PBDEs among a multi-ethnic, low-income cohort of pregnant women enrolled from highly urban communities in New York City between years 2009–2010. Methods: During the first half of pregnancy we collected 316 maternal serum samples and administered an extensive questionnaire including items on demographics, diet and lifestyle. We measured 12 PBDE congeners in blood samples. Using bivariate and multivariate approaches, we regressed the most commonly detected PBDE congeners (PBDE-47, -99, -100 and -153) against potential demographic, dietary and lifestyle predictor variables. Results: At least one PBDE congener was detected in each serum sample. Our analyses demonstrate unique predictor patterns for PBDE-47, -99, -100 and -153 based on demographic, lifestyle and dietary characteristics of women. Higher education and increased use of household electronics were associated with higher levels of all 4 congeners. Six characteristics were associated with PBDE-153 serum concentrations, more than for any other congener. These include maternal education, household income, body mass index, solid dairy consumption, processed meat consumption and frequent use of household electronics. Conclusions: PBDE exposure in this widespread in this cohort, though levels are lower than previous assessments of US pregnant women. Lower levels may be in response to legislation restricting the production, sale and use of these compounds. In our cohort, we did not observe any individual predictor or a consistent pattern of several predictors representing a significant source of PBDE exposure. These data suggest that legislation and policy may be more effective at reducing exposure than personal lifestyle modifications

Topological network properties of resting-state functional connectivity patterns are associated with metal mixture exposure in adolescents

IntroductionAdolescent exposure to neurotoxic metals adversely impacts cognitive, motor, and behavioral development. Few studies have addressed the underlying brain mechanisms of these metal-associated developmental outcomes. Furthermore, metal exposure occurs as a mixture, yet previous studies most often consider impacts of each metal individually. In this cross-sectional study, we investigated the relationship between exposure to neurotoxic metals and topological brain metrics in adolescents. MethodsIn 193 participants (53% females, ages: 15-25 years) enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we measured concentrations of four metals (manganese, lead, copper, and chromium) in multiple biological media (blood, urine, hair, and saliva) and acquired resting-state functional magnetic resonance imaging scans. Using graph theory metrics, we computed global and local efficiency (global:GE; local:LE) in 111 brain areas (Harvard Oxford Atlas). We used weighted quantile sum (WQS) regression models to examine association between metal mixtures and each graph metric (GE or LE), adjusted for sex and age. ResultsWe observed significant negative associations between the metal mixture and GE and LE [beta GE = -0.076, 95% CI (-0.122, -0.031); beta LE= -0.051, 95% CI (-0.095, -0.006)]. Lead and chromium measured in blood contributed most to this association for GE, while chromium measured in hair contributed the most for LE. DiscussionOur results suggest that exposure to this metal mixture during adolescence reduces the efficiency of integrating information in brain networks at both local and global levels, informing potential neural mechanisms underlying the developmental toxicity of metals. Results further suggest these associations are due to combined joint effects to different metals, rather than to a single metal

The Luria-Nebraska Neuropsychological Battery Neuromotor Tasks: From Conventional to Image-Derived Measures

Background: Sensorimotor difficulties significantly interfere with daily activities, and when undiagnosed in early life, they may increase the risk of later life cognitive and mental health disorders. Subtests from the Luria-Nebraska Neuropsychological Battery (LNNB) discriminate sensorimotor impairments predictive of sensorimotor dysfunction. However, scoring the LNNB sensorimotor assessment is highly subjective and time consuming, impeding the use of this task in epidemiologic studies. Aim: To train and validate a novel automated and image-derived scoring approach to the LNNB neuro-motor tasks for use in adolescents and young adults. Methods: We selected 46 adolescents (19.6 +/- 2.3 years, 48% male) enrolled in the prospective Public Health Impact of Metal Exposure (PHIME) study. We visually recorded the administration of five conventional sensorimotor LNNB tasks and developed automated scoring alternatives using a novel mathematical approach combining optic flow fields from recorded image sequences on a frame-by-frame basis. We then compared the conventional and image-derived LNNB task scores using Pearson's correlations. Finally, we provided the accuracy of the novel scoring approach with Receiver Operating Characteristic (ROC) curves and the area under the ROC curves (AUC). Results: Image-derived LNNB task scores strongly correlated with conventional scores, which were assessed and confirmed by multiple administrators to limit subjectivity (Pearson's correlation >= 0.70). The novel image-derived scoring approach discriminated participants with low motility

Biospecimens and the ABCD study: Rationale, methods of collection, measurement and early data

Biospecimen collection in the Adolescent Brain Cognitive Development (ABCD) study – of hair samples, shed deciduous (baby) teeth, and body fluids – will serve dual functions of screening for study eligibility, and providing measures of biological processes thought to predict or correlate with key study outcomes on brain and cognitive development. Biosamples are being collected annually to screen for recency of drug use prior to the neuroimaging or cognitive testing visit, and to store for the following future studies: (1) on the effects of exposure to illicit and recreational drugs (including alcohol and nicotine); (2) of pubertal hormones on brain and cognitive developmental trajectories; (3) on the contribution of genomics and epigenomics to child and adolescent development and behavioral outcomes; and (4) with pre- and post-natal exposure to environmental neurotoxicants and drugs of abuse measured from novel tooth analyses. The present manuscript describes the rationales for inclusion and selection of the specific biospecimens, methodological considerations for each measure, future plans for assessment of biospecimens during follow-up visits, and preliminary ABCD data to illustrate methodological considerations. Keywords: Biospecimens, ABCD study, Substance use, Gonadal hormones, Genetics, Environmental exposure