Using Biologic Markers in Blood to Assess Exposure to Multiple Environmental Chemicals for Inner-City Children 3–6 Years of Age

We assessed concurrent exposure to a mixture of > 50 environmental chemicals by measuring the chemicals or their metabolites in the blood of 43 ethnically diverse children (3–6 years of age) from a socioeconomically disadvantaged neighborhood in Minneapolis. Over a 2-year period, additional samples were collected every 6–12 months from as many children as possible. We analyzed blood samples for 11 volatile organic compounds (VOCs), 2 heavy metals (lead and mercury, 11 organochlorine (OC) pesticides or related compounds, and 30 polychlorinated biphenyl (PCB) congeners. The evidence suggests that numerous VOCs originated from common sources, as did many PCBs. Longitudinal measurements indicate that between-child variance was greater than within-child variance for two VOCs (benzene, toluene), for both heavy metals (Pb, Hg), for all detectable OC pesticides, and for 15 of the measured PCB congeners (74, 99, 101, 118, 138–158, 146, 153, 156, 170, 178, 180, 187, 189, 194, 195). Despite the relatively small sample size, highest measured blood levels of 1,4-dichlorobenzene, styrene, m-/p-xylene, Pb, Hg, heptachlor epoxide, oxychlordane, dichlorodiphenyldichloroethene (p,p′-DDE), trans-nonachlor, and PCB congeners 74, 99, 105, 118, 138, 146, 153, 156, 170, and 180 were comparable with or higher than 95th percentile measurements of older children and adults from national surveys. Results demonstrate that cumulative exposures to multiple environmental carcinogens and neurotoxins can be comparatively high for children from a poor inner-city neighborhood

Volatile Organic Compounds and Pulmonary Function in the Third National Health and Nutrition Examination Survey, 1988–1994

BACKGROUND: Volatile organic compounds (VOCs) are present in much higher concentrations indoors, where people spend most of their time, than outdoors and may have adverse health effects. VOCs have been associated with respiratory symptoms, but few studies address objective respiratory end points such as pulmonary function. Blood levels of VOCs may be more indicative of personal exposures than are air concentrations; no studies have addressed their relationship with respiratory outcomes. OBJECTIVE: We examined whether concentrations of 11 VOCs that were commonly identified in blood from a sample of the U.S. population were associated with pulmonary function. METHODS: We used data from 953 adult participants (20–59 years of age) in the Third National Health and Nutrition Examination Survey (1988–1994) who had VOC blood measures as well as pulmonary function measures. Linear regression models were used to evaluate the relationship between 11 VOCs and measures of pulmonary function. RESULTS: After adjustment for smoking, only 1,4-dichlorobenzene (1,4-DCB) was associated with reduced pulmonary function. Participants in the highest decile of 1,4-DCB concentration had decrements of −153 mL [95% confidence interval (CI), −297 to −8] in forced expiratory volume in 1 sec and −346 mL/sec (95% CI, −667 to −24) in maximum mid-expiratory flow rate, compared with participants in the lowest decile. CONCLUSIONS: Exposure to 1,4-DCB, a VOC related to the use of air fresheners, toilet bowl deodorants, and mothballs, at levels found in the U.S. general population, may result in reduced pulmonary function. This common exposure may have long-term adverse effects on respiratory health

Biologic Monitoring of Exposure to Environmental Chemicals throughout the Life Stages: Requirements and Issues for Consideration for the National Children’s Study

Biomonitoring of exposure is a useful tool for assessing environmental exposures. The matrices available for analyses include blood, urine, breast milk, adipose tissue, and saliva, among others. The sampling can be staged to represent the particular time period of concern: preconceptionally from both parents, from a pregnant woman during each of the three trimesters, during and immediately after childbirth, from the mother postnatally, and from the child as it develops to 21 years of age. The appropriate sample for biomonitoring will depend upon matrix availability, the time period of concern for a particular exposure or health effect, and the different classes of environmental chemicals to be monitored. This article describes the matrices available for biomonitoring during the life stages being evaluated in the National Children’s Study; the best biologic matrices for exposure assessment for each individual chemical class, including consideration of alternative matrices; the analytical methods used for analysis, including quality control procedures and less costly alternatives; the costs of analysis; optimal storage conditions; and chemical and matrix stability during long-term storage

Functional Electrical Stimulation of Intrinsic Laryngeal Muscles under Varying Loads in Exercising Horses

Bilateral vocal fold paralysis (BVCP) is a life threatening condition and appears to be a good candidate for therapy using functional electrical stimulation (FES). Developing a working FES system has been technically difficult due to the inaccessible location and small size of the sole arytenoid abductor, the posterior cricoarytenoid (PCA) muscle. A naturally-occurring disease in horses shares many functional and etiological features with BVCP. In this study, the feasibility of FES for equine vocal fold paralysis was explored by testing arytenoid abduction evoked by electrical stimulation of the PCA muscle. Rheobase and chronaxie were determined for innervated PCA muscle. We then tested the hypothesis that direct muscle stimulation can maintain airway patency during strenuous exercise in horses with induced transient conduction block of the laryngeal motor nerve. Six adult horses were instrumented with a single bipolar intra-muscular electrode in the left PCA muscle. Rheobase and chronaxie were within the normal range for innervated muscle at 0.55±0.38 v and 0.38±0.19 ms respectively. Intramuscular stimulation of the PCA muscle significantly improved arytenoid abduction at all levels of exercise intensity and there was no significant difference between the level of abduction achieved with stimulation and control values under moderate loads. The equine larynx may provide a useful model for the study of bilateral fold paralysis

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al

Fin-Tail Coordination during Escape and Predatory Behavior in Larval Zebrafish

Larval zebrafish innately perform a suite of behaviors that are tightly linked to their evolutionary past, notably escape from threatening stimuli and pursuit and capture of prey. These behaviors have been carefully examined in the past, but mostly with regard to the movements of the trunk and tail of the larvae. Here, we employ kinematics analyses to describe the movements of the pectoral fins during escape and predatory behavior. In accord with previous studies, we find roles for the pectoral fins in slow swimming and immediately after striking prey. We find novel roles for the pectoral fins in long-latency, but not in short-latency C-bends. We also observe fin movements that occur during orienting J-turns and S-starts that drive high-velocity predatory strikes. Finally, we find that the use of pectoral fins following a predatory strike is scaled to the velocity of the strike, supporting a role for the fins in braking. The implications of these results for central control of coordinated movements are discussed, and we hope that these results will provide baselines for future analyses of cross-body coordination using mutants, morphants, and transgenic approaches

Assessing Fish and Motile Fauna around Offshore Windfarms Using Stereo Baited Video

There remains limited knowledge of how offshore windfarm developments influence fish assemblages, particularly at a local scale around the turbine structures. Considering the existing levels of anthropogenic pressures on coastal fish populations it is becoming increasingly important for developers and environmental regulators to gain a more comprehensive understanding of the factors influencing fish assemblages. Improving our ability to assess such fish populations in close proximity to structures will assist in increasing this knowledge. In the present study we provide the first trial use of Baited Remote Underwater Stereo-Video systems (stereo BRUVs) for the quantification of motile fauna in close proximity to offshore wind turbines. The study was conducted in the Irish Sea and finds the technique to be a viable means of assessing the motile fauna of such environments. The present study found a mixture of species including bottom dwellers, motile crustaceans and large predatory fish. The majority of taxa observed were found to be immature individuals with few adult individuals recorded. The most abundant species were the angular crab (Goneplax rhomboides) and the small-spotted catshark (Scyliorhinus canicula). Of note in this study was the generally low abundance and diversity of taxa recorded across all samples, we hypothesise that this reflects the generally poor state of the local fauna of the Irish Sea. The faunal assemblages sampled in close proximity to turbines were observed to alter with increasing distance from the structure, species more characteristic of hard bottom environments were in abundance at the turbines (e.g. Homarus gammarus, Cancer pagarus, Scyliorhinus spp.) and those further away more characteristic of soft bottoms (e.g. Norwegian Lobster). This study highlights the need for the environmental impacts of offshore renewables on motile fauna to be assessed using targeted and appropriate tools. Stereo BRUVs provide one of those tools, but like the majority of methods for sampling marine biota, they have limitations. We conclude our paper by providing a discussion of the benefits and limitations of using this BRUV technique for assessing fauna within areas close to offshore windfarms

Evaluation of Jackknife and Bootstrap for Defining Confidence Intervals for Pairwise Agreement Measures

Several research fields frequently deal with the analysis of diverse classification results of the same entities. This should imply an objective detection of overlaps and divergences between the formed clusters. The congruence between classifications can be quantified by clustering agreement measures, including pairwise agreement measures. Several measures have been proposed and the importance of obtaining confidence intervals for the point estimate in the comparison of these measures has been highlighted. A broad range of methods can be used for the estimation of confidence intervals. However, evidence is lacking about what are the appropriate methods for the calculation of confidence intervals for most clustering agreement measures. Here we evaluate the resampling techniques of bootstrap and jackknife for the calculation of the confidence intervals for clustering agreement measures. Contrary to what has been shown for some statistics, simulations showed that the jackknife performs better than the bootstrap at accurately estimating confidence intervals for pairwise agreement measures, especially when the agreement between partitions is low. The coverage of the jackknife confidence interval is robust to changes in cluster number and cluster size distribution

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Pramipexole effects on startle gating in rats and normal men

Dopamine D3 receptors regulate sensorimotor gating in rats, as evidenced by changes in prepulse inhibition (PPI) of startle after acute administration of D3 agonists and antagonists. In this study, we tested the effects of the D3-preferential agonist, pramipexole, on PPI in normal men and Sprague–Dawley rats. Acoustic startle and PPI were tested in clinically normal men, comparing the effects of placebo vs. 0.125 mg (n = 20) or placebo vs. 0.1875 mg (n = 20) pramipexole, in double blind, crossover designs. These measures were also tested in male Sprague–Dawley rats using a parallel design [vehicle vs. 0.1 mg/kg (n = 8), vehicle vs. 0.3 mg/kg (n = 8) or vehicle vs. 1.0 mg/kg pramipexole (n = 8)]. Autonomic and subjective measures of pramipexole effects and several personality instruments were also measured in humans. Pramipexole increased drowsiness and significantly increased PPI at 120-ms intervals in humans; the latter effect was not moderated by baseline PPI or personality scale scores. In rats, pramipexole causes a dose-dependent reduction in long-interval (120 ms) PPI, while low doses actually increased short-interval (10–20 ms) PPI. Effects of pramipexole on PPI in rats were independent of baseline PPI and changes in startle magnitude. The preferential D3 agonist pramipexole modifies PPI in humans and rats. Unlike indirect DA agonists and mixed D2/D3 agonists, pramipexole increases long-interval PPI in humans, in a manner that is independent of baseline PPI and personality measures. These findings are consistent with preclinical evidence for differences in the D2- and D3-mediated regulation of sensorimotor gating