Veterans of Operation Desert Storm/Desert Shield – the 1991 Gulf War (GW) – are a unique population who returned from theater with multiple health complaints and disorders. Studies in the U.S. and elsewhere have consistently concluded that approximately 25–32% of this population suffers from a disorder characterized by symptoms that vary somewhat among individuals and include fatigue, headaches, cognitive dysfunction, musculoskeletal pain, and respiratory, gastrointestinal and dermatologic complaints. Gulf War illness (GWI) is the term used to describe this disorder. In addition, brain cancer occurs at increased rates in subgroups of GW veterans, as do neuropsychological and brain imaging abnormalities.Chemical exposures have become the focus of etiologic GWI research because nervous system symptoms are prominent and many neurotoxicants were present in theater, including organophosphates (OPs), carbamates, and other pesticides; sarin/cyclosarin nerve agents, and pyridostigmine bromide (PB) medications used as prophylaxis against chemical warfare attacks. Psychiatric etiologies have been ruled out.This paper reviews the recent literature on the health of 1991 GW veterans, focusing particularly on the central nervous system and on effects of toxicant exposures. In addition, it emphasizes research published since 2008, following on an exhaustive review that was published in that year that summarizes the prior literature (RACGWI, 2008).We conclude that exposure to pesticides and/or to PB are causally associated with GWI and the neurological dysfunction in GW veterans. Exposure to sarin and cyclosarin and to oil well fire emissions are also associated with neurologically based health effects, though their contribution to development of the disorder known as GWI is less clear. Gene-environment interactions are likely to have contributed to development of GWI in deployed veterans. The health consequences of chemical exposures in the GW and other conflicts have been called “toxic wounds” by veterans. This type of injury requires further study and concentrated treatment research efforts that may also benefit other occupational groups with similar exposure-related illnesses.

High levels of depression, anxiety and distress are reported in adults exposed to childhood sexual and physical abuse. These findings require increased awareness for the potential needs of adults exposed to child abuse and public health interventions to prevent child abuse.

Recent theoretical and experimental work indicates that neurons tune themselves to maintain target levels of excitation by modulating ion channel expression and synaptic strengths. As a result, functionally equivalent circuits can produce similar activity despite disparate underlying network and cellular properties. To experimentally test the extent to which synaptic and intrinsic conductances can produce target activity in the presence of variability in neuronal intrinsic properties, we used the dynamic clamp to create hybrid two-cell circuits built from four types of stomatogastric neurons coupled to the same model Morris-Lecar neuron by reciprocal inhibition. We measured six intrinsic properties (input resistance, minimum membrane potential, firing rate in response to ϩ1 nA of injected current, slope of the frequency-current curve, spike height, and spike voltage threshold) of dorsal gastric, gastric mill, lateral pyloric, and pyloric dilator neurons from male crabs of the species Cancer borealis. The intrinsic properties varied twofold to sevenfold in each cell type. We coupled each biological neuron to the Morris-Lecar model with seven different values of inhibitory synaptic conductance and also used the dynamic clamp to add seven different values of an artificial h-conductance, thus creating 49 different circuits for each biological neuron. Despite the variability in intrinsic excitability, networks formed from each neuron produced similar circuit performance at some values of synaptic and h-conductances. This work experimentally confirms results from previous modeling studies; tuning synaptic and intrinsic conductances can yield similar circuit outputs from neurons with variable intrinsic excitability.

Recent work argues that similar network performance can result from highly variable sets of network parameters, raising the question of whether neuromodulation can be reliable across individuals with networks with different sets of synaptic strengths and intrinsic membrane conductances. To address this question, we used the dynamic clamp to construct 2-cell reciprocally inhibitory networks from gastric mill (GM) neurons of the crab stomatogastric ganglion. When the strength of the artificial inhibitory synapses (gsyn) and the conductance of an artificial Ih (gh) were varied with the dynamic clamp, a variety of network behaviors resulted, including regions of stable alternating bursting. Maps of network output as a function of gsyn and gh were constructed in normal saline and again in the presence of serotonin or oxotremorine. Both serotonin and oxotremorine depolarize and excite isolated individual GM neurons, but by different cellular mechanisms. Serotonin and oxotremorine each increased the size of the parameter regions that supported alternating bursting, and, on average, increased burst frequency. Nonetheless, in both cases some parameter sets within the sample space deviated from the mean population response and decreased in frequency. These data provide insight into why pharmacological treatments that work in most individuals can generate anomalous actions in a few individuals, and they have implications for understanding the evolution of nervous systems. dynamic clamp ͉ evolution ͉ serotonin ͉ stomatogastric ganglion ͉ oscillator H ow different are the brains in a population of healthy individuals of the same species? Both modeling and experimental studies demonstrate that similar circuit function can result from a large variation in the synaptic and intrinsic conductances that contribute to circuit function (1-11). This finding suggests that each individual could, during development, build a brain that differs significantly from all others and poses the question of whether circuits with diverse underlying structure, yet similar behavior, can respond reliably (12, 13) to neuromodulatory substances that alter brain states (14-21). Therefore, we used the dynamic clamp (22, 23) to construct 2-cell circuits (24) from neurons of the crab stomatogastric ganglion (STG). The strength of the reciprocal inhibitory synapses (g syn ) and the conductance of an artificial I h (g h ) were varied (24), and the resulting activity patterns were recorded in control saline and in response to 2 neuromodulatory substances, serotonin and the muscarinic agonist, oxotremorine.In these hybrid experiments, the intrinsic properties of these 2 biological neurons vary between each other and across preparations while 2 of the important parameters for network performance are under experimental control. This method ensures that the variability intrinsic to biological systems is retained, while allowing access to some of the parameters controlling network performance. Results and DiscussionWe used gastric mill (GM) neurons of the STG of t...

Background: Former American football players have a higher prevalence of cognitive impairment than that of the US general population. It remains unknown what aspects of playing football are associated with neuropsychiatric outcomes. Hypothesis: It was hypothesized that seasons of professional football, playing position, and experience of concussions were associated with cognition-related quality of life (QOL) and indicators of depression and anxiety. Study Design: Descriptive epidemiology study. Methods: The authors examined whether seasons of professional football, playing position, and experience of concussions, as measured by self-report of 10 symptoms, were associated with cognition-related QOL and indicators of depression and anxiety in a cross-sectional survey conducted 2015 to 2017. Cognition-related QOL was measured by the short form of the Quality of Life in Neurological Disorders: Applied Cognition–General Concerns. The Patient Health Questionnaire–4 measured depression and anxiety symptoms. Of 13,720 eligible men with apparently valid contact information, 3506 players returned a questionnaire at the time of this analysis (response rate = 25.6%). Results: Seasons of professional play (risk ratio [RR] per 5 seasons = 1.19, 95% CI = 1.06-1.34) and playing position were associated with cognition-related QOL. Each 5 seasons of play was associated with 9% increased risk of indicators of depression at borderline statistical significance ( P = .05). When compared with former kickers, punters, and quarterbacks, men who played any other position had a higher risk of poor cognition-related QOL, depression, and anxiety. Concussion symptoms were strongly associated with poor cognition-related QOL (highest concussion quartile, RR = 22.3, P < .001), depression (highest quartile, RR = 6.0, P < .0001), and anxiety (highest quartile, RR = 6.4, P < .0001), even 20 years after last professional play. Conclusion: The data suggest that seasons of play and playing position in the NFL are associated with lasting neuropsychiatric health deficits. Additionally, poor cognition-related QOL, depression, and anxiety appear to be associated with concussion in the long term.

The stomatogastric ganglion (STG) is an excellent model for studying cellular and network interactions because it contains a relatively small number of cells (approximately 25 in C. borealis) which are well characterized. The cells in the STG exhibit a broad range of outputs and are responsible for the motor actions of the stomach. The stomach contains the gastric mill which breaks down food with three internal teeth, and the pylorus which filters the food before it reaches the midgut. The STG produces two rhythmic outputs to control the gastric mill and pylorus known as central pattern generators (CPGs). Each cell in the STG can participate in one or both of these rhythms. These CPGs allow for the study of neuromodulation, homeostasis, cellular and network variability, network development, and network recovery.The dissection of the stomatogastric nervous system (STNS) from the Jonah crab (Cancer borealis) is done in two parts; the gross and fine dissection. In the gross dissection the entire stomach is dissected from the crab. During the fine dissection the STNS is extracted from the stomach using a dissection microscope and micro-dissection tools (see figure 1). The STNS includes the STG, the oesophageal ganglion (OG), and the commissural ganglia (CoG) as well as the nerves that innervate the stomach muscles. Here, we show how to perform a complete dissection of the STNS in preparation for an electrophysiology experiment where the cells in the STG would be recorded from intracellularly and the peripheral nerves would be used for extracellular recordings. The proper technique for finding the desired nerves is shown as well as our technique of desheathing the ganglion to reveal the somata and neuropil.

In populations exposed to heavy metals, there are few biomarkers that capture intermediate exposure windows. We sought to determine the correlation between toenail metal concentrations and prior 12 month work activity in welders with variable, metal-rich, welding fume exposures. Forty-eight participants, recruited through a local union, provided 69 sets of toenail clippings. Union-supplied and worker verified personal work histories were used to quantify hours welded and respirator use. Toenail samples were digested and analyzed for lead (Pb), manganese (Mn), cadmium (Cd), nickel (Ni) and arsenic (As) using ICP-MS. Spearman correlation coefficients were used to examine the correlation between toenail metal concentrations. Using mixed models to account for multiple participation times, we divided hours welded into three-month intervals and examined how weld hours correlated with log-transformed toenail Pb, Mn, Cd, Ni and As concentrations. Highest concentrations were found for Ni, followed by Mn, Pb and As, and Cd. All of the metals were significantly correlated with one another (rho range=0.28-0.51), with the exception of Ni and As (rho=0.20, p=0.17). Using mixed models adjusted for age, respirator use, smoking status and BMI, we found that Mn was associated with weld hours 7-9 months prior to clipping (p = 0.003), Pb was associated with weld hours 10-12 months prior to clipping (p=0.03) and over the entire year (p=0.04). Cd was associated with weld hours 10-12 months prior to clipping (p=0.05), and also with the previous year's total hours welded (p=0.02). The association between Ni and weld hours 7-9 months prior to clipping approached significance (p=0.06). Toenail metal concentrations were not associated with the long-term exposure metric, years as a welder. Results suggest Mn, Pb, and Cd may have particular windows of relevant exposure that reflect work activity. In a population with variable exposure, toenails may serve as useful COMPETING INTERESTSThe authors declare they have no competing financial interests. HHS Public Access

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