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Search Results: 1 - 10 of 229524 matches for " Philip R Kym "
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TRPA1 modulation of spontaneous and mechanically evoked firing of spinal neurons in uninjured, osteoarthritic, and inflamed rats
Steve McGaraughty, Katharine L Chu, Richard J Perner, Stan DiDomenico, Michael E Kort, Philip R Kym
Molecular Pain , 2010, DOI: 10.1186/1744-8069-6-14
Abstract: Systemic injection of A-967079 (30 μmol/kg, i.v.) decreased the responses of wide dynamic range (WDR), and nociceptive specific (NS) neurons following noxious pinch stimulation of the ipsilateral hind paw in uninjured and CFA-inflamed rats. Similarly, A-967079 reduced the responses of WDR neurons to high-intensity mechanical stimulation (300 g von Frey hair) of the knee joint in both OA and OA-sham rats. WDR neuronal responses to low-intensity mechanical stimulation (10 g von Frey hair) were also reduced by A-967079 administration to CFA-inflamed rats, but no effect was observed in uninjured rats. Additionally, the spontaneous activity of WDR neurons was decreased after A-967079 injection in CFA-inflamed rats but was unaltered in uninjured, OA, and OA-sham animals.Blockade of TRPA1 receptors disrupts transmission of high-intensity mechanical stimulation to the spinal cord in both uninjured and injured rats indicating that TRPA1 receptors have an important role in noxious mechanosensation in both normal and pathological conditions. TRPA1 receptors also contribute to the transmission of low-intensity mechanical stimulation, and to the modulation of spontaneous WDR firing, but only after an inflammatory injury.The transient receptor potential (TRP)A1 receptor is part of a larger family of TRP ion channels that includes TRPV, TRPM, TRPC, TRPN, TRPP, and TRPML [1-3]. TRPA1 is expressed in small and medium-sized peptidergic primary afferent sensory neurons that also express TRPV1 [4-8]. A recent report has also demonstrated localization of TRPA1 to a subclass of large diameter primary afferent sensory neurons and epidermal kerantinocytes [8]. TRPA1 is activated by a variety of chemical irritants that include allyl isothiocyanate (mustard oil), allicin, gingerol, cinnamaldehyde, eugenol, and methysalicylate [5,6,9,10]. Local application of these TRPA1 agonists induces spontaneous pain in humans [11], as well as nocifensive behaviors and hypersensitivity to peripheral stimu
Pore dilation occurs in TRPA1 but not in TRPM8 channels
Jun Chen, Donghee Kim, Bruce R Bianchi, Eric J Cavanaugh, Connie R Faltynek, Philip R Kym, Regina M Reilly
Molecular Pain , 2009, DOI: 10.1186/1744-8069-5-3
Abstract: Abundantly expressed in sensory neurons, TRPV1, TRPA1 and TRPM8 are involved in sensory function, pain and neurogenic inflammation [1]. The function of these ion channels has been attributed to their ability to pass certain ion species across the plasma membrane. Once activated, TRPV1, TRPA1 and TRPM8 are permeable to small cations such as Ca2+, K+, Na+; hence, channel activation simultaneously depolarizes the plasma membrane and raises intracellular Ca2+, which subsequently triggers a variety of physiological processes. By analogy to voltage-gated K+ channels, it is assumed that ion selectivity of TRP channels should be an invariant signature to the respective channel. However, this notion has been challenged recently. When activated, TRPV1 exhibits time and agonist-dependent changes in ion selectivity [2]. In fact, TRPV1 undergoes pore dilation and allows permeation of large organic cations, including spermine (202.3 Da), NMDG (195.2 Da), Yo-Pro (376 Da), gentamycin (477.6 Da) and QX-314 [3-7]. Here we explored whether TRPA1 and TRPM8 undergo pore dilation by examining Yo-Pro uptake and changes in ion selectivity upon channel activation.Yo-Pro is a divalent cation impermeable to the plasma membrane. However, under certain conditions, it can enter cells, bind nucleic acids and emit fluorescence. Hence the uptake of Yo-Pro has been used previously as an indicator of pore dilation [2,8,9]. In HEK293-F cells transiently expressing rat TRPA1, allyl isothiocyanate (AITC) evoked robust increases in intracellular Ca2+ (Fig. 1A). Concomitantly, AITC also induced Yo-Pro uptake in a concentration-dependent manner (Fig. 1B). At higher concentrations of AITC (100 or 300 μM), the increase in fluorescence was immediately noticeable and continued to increase for about 50 min. In addition, AITC also induced Ca2+ influx and Yo-Pro uptake in cells expressing human TRPA1 and mouse TRPA1, but not in untransfected cells (data not shown). In cells expressing human TRPM8, menthol activat
Accurately Measuring Inspection Time with Computers  [PDF]
A. Kym Preiss, Nicholas R. Burns
International Journal of Intelligence Science (IJIS) , 2012, DOI: 10.4236/ijis.2012.24013
Abstract: Accurately measuring inspection time (IT) with computers requires several considerations. They are: 1) Screen redraw period; 2) Synchronous and timely image presentation; 3) Stimulus duration timing; 4) Image scale invariance; 5) Stan dardized presentation format (of which image scale invariance is a part). The first consideration dictates a minimum duration available for measuring IT. The second and third are necessary for accurate stimulus duration. The fourth is necessary to provide scale invariant images, that is, images with the same visual angle at a given viewing distance on any computer. And the fifth ensures that participants everywhere respond to the same task. Our computer program em bodies these elements and we make it freely available to any interested party. Data to establish validity and reliability are presented, and normative data on 2518 participants aged 6 to 92 years are available.
Polychlorinated Biphenyls in Whole-Body Field Mice Collected Upgradient and Downgradient of a Sediment Retention Structure in Los Alamos Canyon, Los Alamos National Laboratory, New Mexico, USA  [PDF]
Philip R. Fresquez
Journal of Environmental Protection (JEP) , 2014, DOI: 10.4236/jep.2014.52013

Polychlorinated biphenyl (PCBs) congeners were measured in (unwashed) whole-body field (deer) mice (Peromyscus maniculaltus) collected directly upgradient from a sediment retention structure (weir) within Los Alamos Canyon (LAC), Los Alamos National Laboratory (LANL), New Mexico, USA, from 2007 through 2013. Samples were also collected approximately 8 km downgradient of the retention structure in 2009 and 2013. LAC, a major drainage that crosses LANL lands, contains legacy waste, including PCBs, and occasionally discharges storm water and snowmelt flows to the Rio Grande approximately 8.8 km away from the weir. The Rio Grande is the major waterway that flows southward across the state. The weir was constructed across the channel on the northeastern boundary of LANL in late 2000 to help contain sediments mobilized by floodwaters as a result of a large wildfire in early 2000 that burned forest lands west and adjacent to LANL. Total PCBs in field mice directly upgradient of the sediment retention structure from 2007 through 2012 were significantly greater (p < 0.05) than in field mice collected from background locations but decreased in concentration over time; by 2013 the levels were statistically similar (p > 0.05) to background. The highest mean total PCB concentration in field mice was below the levels that may negatively impact field mice population attributes. Total PCBs in field mice collected 8 km below the sediment retention structure in 2009 were lower than field mice collected from behind the weir and decreased over time; also by 2013, the amount of PCBs in field mice 8 km below the sediment retention structure were not significantly different (p > 0.05) from background. The rank order of concentrations of ICES 7 PCB congeners

The Financial Life Well-Lived: Psychological Benefits of Financial Planning
Kym Irving
Australasian Accounting Business and Finance Journal , 2012,
Tarveen K.R. Singh,Kym J. Guelfi,Grant Landers,Brian Dawson
Journal of Sports Science and Medicine , 2010,
Abstract: Most team sports are characterised by repeated short maximal sprint efforts interspersed with longer periods of active recovery or rest. Although a variety of testing protocols have been devised to simulate these activity patterns under controlled conditions, a common limitation is the lack of 'body contact' to simulate the tackling efforts seen in contact sports. Therefore, the purpose of this study was to assess the reliability of a simulated team game protocol with and without 'contact'. Eleven male, team-sport athletes (mean ± SD; age 22 ± 2 yr; BMI 23.0 ± 1.7 kg·m-2) completed four separate testing trials; two 'non-contact' trials (NCON) and two 'contact' (CON) trials of a simulated game to determine the reliability of a range of team sport performance indicators including repeated 15-m sprint time, vertical jump height, heart rate response and ratings of perceived exertion (RPE). The team game protocol involved four sets of 15-min of intermittent running around a circuit replicating the movement patterns observed in team sports, either with or without simulated contact. Within-subject reliability of each performance measure was determined by expressing the typical error of measurement as the coefficient of variation, as well as determining intra-class correlations. Both CON and NCON produced reliable results for a variety of team sport performance indicators including repeated 15-m sprint time, vertical jump height, heart rate response and RPE. Repeated sprint and jump performance declined over time throughout the simulated game (p < 0.05), while heart rate and RPE increased. There was no difference in these performance measures between CON and NCON protocols. As such, these simulated game protocols provide reliable options for assessing team game performance parameters in response to training or other interventions under controlled conditions
Bioassessment of the Rio Grande Upstream and Downstream of Los Alamos National Laboratory,New Mexico, USA  [PDF]
Philip R. Fresquez, Gerald Z. Jacobi
Journal of Environmental Protection (JEP) , 2012, DOI: 10.4236/jep.2012.311176
Abstract: Benthic macroinvertebrates (aquatic insects) were collected from the Rio Grande upstream and downstream of Los Alamos Canyon (LAC), a major drainage that crosses Los Alamos National Laboratory (LANL) lands in northern New Mexico, USA. LAC contains legacy waste, including radionuclides and polychlorinated biphenyls, and occasionally discharges storm water and snowmelt flows to the Rio Grande. The Rio Grande is the major waterway that flows southward across the state. In 2009, rock baskets were placed in waters 61- to 76-cm-deep within each reach (five per reach), and, after approximately 6 weeks of colonization, the rock baskets were retrieved. All samples were sorted completely and organisms were identified to the lowest possible taxonomic level. Both reaches in 2009 were dominated by the collector filtering net-spinning caddisfly, Hydropsyche occidentalis. In 2011, benthic macroinvertebrates were collected using D kick nets from shallow riffle locations (15- to 31-cm depth) from each reach (six per reach). These samples were collected after post- (Las Conchas) fire flooding events moved sediment and ash through the two study areas—the downstream reach, however, was affected by higher flows and greater number of flooding events than those affecting the upstream reach. Each kick net sample consisted of ten 1-m (kick) samples. The 10 subsamples were composited and organisms were picked from randomly selected cells in a sorting pan until 500 organisms had been identified to the lowest possible taxonomic level. Both reaches in 2011 were dominated by the collector-gathering mayfly, Baetis tricaudatus. A bioassessment of the downstream reach compared with the upstream (reference) reach was conducted by scoring 10 metrics related to the structure and function of the benthic macroinvertebrate community. While 2009 ranked at the highest level (nonimpaired), 2011 ranked a level lower (slightly impaired). The slightly lower bioassessment score of the downstream reach in 2011 may be a result of flooding impacts following the Las Conchas fire rather than of LANL operations. Overall, based on the similarity of benthic macroinvertebrate metrics between reaches and the composition of benthic macroinvertebrates favoring pollution intolerant taxa, LANL influences, if any, via the LAC system to the Rio Grande are not significantly impacting water quality of the Rio Grande.
Examining the Effects of Environmental Policy on Shale Gas Production: The Case of Alberta, Canada  [PDF]
Peter Langer, Dale Carl, Philip R. Walsh
Journal of Geoscience and Environment Protection (GEP) , 2017, DOI: 10.4236/gep.2017.59007
Abstract: The increase in natural gas production in North America resulting from the implementation of new technologies related to the fracturing (fracking) of natural gas-bearing shale reservoirs has enhanced the security of supply and lowered energy costs in the continent. Yet the environmental impact associated with shale gas development has raised concerns and debate among energy and environmental policy makers as to how best to address these concerns. As Canada’s largest producer of natural gas, the Province of Alberta is an example of a jurisdiction with numerous regulations for dealing with such environmental risks. This paper applies the CO/RE model of Konschnik and Bolingin examining Alberta’s environmental regulatory framework and the impact; it will have on further shale gas production in the province. Aside from the identification of risks associated with increased seismicity, the results of this examination suggest that the current regulatory environment does not appear to have any adverse effect on current and future shale gas production within the province. Furthermore, Alberta’s environmental regulation has influenced shale gas producers to pursue innovation in technology and engineering practice and has helped establish a collaborative approach to mitigating environmental risk.
Residual Cardiovascular Risk—Is Inflammation the Primary Cause?  [PDF]
David S. Schade, R. Philip Eaton
World Journal of Cardiovascular Diseases (WJCD) , 2018, DOI: 10.4236/wjcd.2018.81007
Abstract: Every cardiovascular clinical trial that has examined the beneficial effects of lowering LDL cholesterol to prevent cardiovascular events has demonstrated residual cardiovascular risk in the interventional treatment group. Residual risk is the term applied to the cardiovascular events (e.g., myocardial infarction, stroke, and cardiovascular death) that occur in spite of being on “optimal” medical therapy. This term is usually applied to secondary intervention studies,?i.e., lipid lowering treatments in subjects who have already had at least one cardiovascular event. Studies that described residual risk have attributed it, at least in part, to the fact that the LDLc has not been lowered sufficiently to stop atherosclerotic plaque formation and rupture into the arterial lumen. However, a recent cardiovascular intervention clinical trial which achieved a very low group median LDLc of 30 mg/dl still demonstrated significant residual risk. Of more importance to reducing residual risk may be addressing the ongoing inflammation in the coronary arteries that results in cellular liberation of cytokines and proteases that attack the atherosclerotic plaque’s fibrous cap. Recent studies have shown that inflammation may act independently of LDL to cause cardiovascular events. This article provides evidence that inflammation is the primary cause of residual risk and will need to be treated as aggressively as LDL lowering if CVD events in the post treatment period are to be significantly reduced. Addressing major risk factors including obesity, diabetes, smoking, hypertension and hyperlipidemia are critical to reducing inflammation. Statins and aspirin are the mainstay medications to reduce ongoing inflammation. However, newer pharmaceuticals may also be required to reduce inflammation to undetectable levels. Targeting inflammation to eradicate residual cardiovascular risk will be the next therapeutic challenge facing primary care physicians.
The Basis of Atherosclerotic Guidelines—Time for a Change?  [PDF]
David S. Schade, R. Philip Eaton
World Journal of Cardiovascular Diseases (WJCD) , 2018, DOI: 10.4236/wjcd.2018.87033
Abstract: Major advances have occurred within the last decade in the understanding of the pathogenesis of coronary artery disease. Not only are the underlying mechanisms now clearly defined, but effective medical therapies are available at low cost and minimal side effects. In spite of these advances, cardiovascular events are still the leading cause of death in the United States and the Western world. Analysis of the many factors involved in the delivery of appropriate cardiovascular care strongly suggests that the primary reason is the overly restrictive guidelines published by medical societies. This article proposes a much broader basis for constructing atherosclerosis clinical guidelines, namely the known pathophysiology of atherosclerosis. If pathophysiology forms the basis of atherosclerotic treatment recommendations, then a risk/benefit analysis can be used to determine appropriate preventive therapy for any specific individual. The result will be that many additional individuals will be eligible for preventive treatment of atherosclerosis, and the saving of many lives at minimal cost will result.
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