603 research outputs found

    Temporal afterglow between two pulses of repetitively pulsed argon-acetylene plasma:measuring electron and negatively charged species densities

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    The temporal afterglow between two pulses of a repetitively pulsed radio-frequency driven low-pressure argon-acetylene plasma is experimentally explored using laser-induced photodetachment combined with microwave cavity resonance spectroscopy. The densities of electrons and negatively charged species, i.e. anions and dust particles, are measured temporally resolved until 1.9 s in the temporal plasma afterglow. Two different plasma-on times are adjusted to investigate the dynamics of anions and dust particles in the afterglow phase. The measurements show that while electrons decay rapidly within the first few milliseconds of the afterglow phase, the negatively charged species reside much longer in the plasma after the plasma is switched off. The electron density decay is measured to be faster for a longer plasma-on time. This effect is attributed to an enhanced recombination rate due to a higher dust particle density and/or size. The density of negatively charged species decays within two different timescales. The first 20 milliseconds of the afterglow is marked with a rapid decay in the negatively charged species density, in contrast with their slow density decay in the second time scale. Moreover, a residual of the negatively charged species densities is detected as long as 1.9 s after extinguishing the plasma.</p

    In vitro pharmacology of fentanyl analogs at the human mu opioid receptor and their spectroscopic analysis

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    Opioids are widely misused and account for almost half of overdose deaths in the United States. The cost in terms of lives, health care, and lost productivity is significant and has been declared a national crisis. Fentanyl is a highly potent mu opioid receptor (MOR) agonist and plays a significant role in the current opioid epidemic; fentanyl and its analogs (fentalogs) are increasingly becoming one of the biggest dangers in the opioid crisis. The availability of fentalogs in the illicit market is thought to play a significant role in the recent increase in opioid‐related deaths. Although there is both rodent homolog in vivo and in vitro data for some fentalogs, prior to this publication very little was known about the pharmacology of many of these illicit compounds at the human MOR (hMOR). Using gas chromatography–mass spectrometry, nuclear magnetic resonance spectroscopy, and in vitro assays, this study describes the spectral and pharmacological properties of 34 fentalogs. The reported spectra and chemical data will allow for easy identification of novel fentalogs in unknown or mixed samples. Taken together these data are useful for law enforcement and clinical workers as they will aid in the identification of fentalogs in unknown samples and can potentially be used to predict physiological effects after exposure.This study reports the basic in vitro pharmacology (affinity, agonist activity, and potencies) of 34 fentanyl analogs at the human mu opioid receptor. In addition, these fentalogs are analyzed spectroscopically using gas chromatography–mass spectrometry and proton nuclear magnetic resonance spectroscopy, to understand structural commonalities and key differences for identification.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156439/2/dta2822.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156439/1/dta2822_am.pd

    Baghdad’s thirdspace: Between liminality, anti-structures and territorial mappings

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    Wedged in-between the dense urban grain of Baghdad, blast walls of t-shaped concrete have littered the streets and neighbourhoods since 2003, after the US led invasion. The idiosyncrasy of these walls lies in their exaggerated spatial liminality. They appear, change location and disappear overnight, and on a daily basis, leaving Iraqis to navigate through labyrinths of in-between spaces. This article critically reveals the new social and power structures that have emerged in the context of the city in response to the condition resulting from this unique urban intervention. This uncanny spatial and social condition of permanent liminality will be analysed through Victor Turner’s critical theories of liminality and anti-structure coupled with Edward Soja’s theory of Thirdspace, interpreting, through a series of territorial mappings, a complex liminal condition in a contested and disrupted city

    Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

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    Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

    Anti-nociceptive and desensitizing effects of olvanil on capsaicin-induced thermal hyperalgesia in the rat

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    Background: Olvanil (NE 19550) is a non-pungent synthetic analogue of capsaicin, the natural pungent ingredient of capsicum which activates the transient receptor potential vanilloid type-1 (TRPV1) channel and was developed as a potential analgesic compound. Olvanil has potent anti-hyperalgesic effects in several experimental models of chronic pain. Here we report the inhibitory effects of olvanil on nociceptive processing using cultured dorsal root ganglion (DRG) neurons and compare the effects of capsaicin and olvanil on thermal nociceptive processing in vivo; potential contributions of the cannabinoid CB1 receptor to olvanil’s anti-hyperalgesic effects were also investigated. Methods: A hot plate analgesia meter was used to evaluate the anti-nociceptive effects of olvanil on capsaicin-induced thermal hyperalgesia and the role played by CB1 receptors in mediating these effects. Single cell calcium imaging studies of DRG neurons were employed to determine the desensitizing effects of olvanil on capsaicin-evoked calcium responses. Statistical analysis used Student’s t test or one way ANOVA followed by Dunnett’s post-hoctest as appropriate. Results: Both olvanil (100 nM) and capsaicin (100 nM) produced significant increases in intracellular calcium concentrations [Ca2+]I in cultured DRG neurons. Olvanil was able to des ensitise TRPV1 responses to further capsaicin exposure more effectively than capsaicin. Intra plantar injection of capsaicin (0.1, 0.3 and 1μg) produced a robust TRPV1-dependant thermal hyperalgesia in rats, whilst olvanil (0.1, 0.3 and 1μg) produced no hyperalgesia, emphasizing its lack of pungency. The highest dose of olvanil significantly reduced the hyperalgesic effects of capsaicin in vivo. Intraplantar injection of the selective cannabinoid CB1 receptor antagonist rimonabant (1μg) altered neither capsaicin-induced thermal hyperalgesia nor the desensitizing properties of olvanil, indicating a lack of involvement of CB1receptors. Conclusions: Olvanil is effective in reducing capsaicin-induced thermal hyperalgesia, probably via directly desensitizingTRPV1 channels in a CB 1 receptor-independent fashion. The results presented clearly support the potential for olvanil in the development of new topical analgesic preparations for treating chronic pain conditions while avoiding the unwanted side effects of capsaicin treatments

    Targeted disruption of Slc2a8 (GLUT8) reduces motility and mitochondrial potential of spermatozoa

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    GLUT8 is a class 3 sugar transport facilitator which is predominantly expressed in testis and also detected in brain, heart, skeletal muscle, adipose tissue, adrenal gland, and liver. Since its physiological function in these tissues is unknown, we generated a Slc2a8 null mouse and characterized its phenotype. Slc2a8 knockout mice appeared healthy and exhibited normal growth, body weight development and glycemic control, indicating that GLUT8 does not play a significant role for maintenance of whole body glucose homeostasis. However, analysis of the offspring distribution of heterozygous mating indicated a lower number of Slc2a8 knockout offspring (30.5:47.3:22.1%, Slc2a8+/+, Slc2a8+/−, and Slc2a8−/− mice, respectively) resulting in a deviation (p = 0.0024) from the expected Mendelian distribution. This difference was associated with lower ATP levels, a reduced mitochondrial membrane potential and a significant reduction of sperm motility of the Slc2a8 knockout in comparison to wild-type spermatozoa. In contrast, number and survival rate of spermatozoa were not altered. These data indicate that GLUT8 plays an important role in the energy metabolism of sperm cells
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