Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain

Gabapentin is a first-line therapy for neuropathic pain but its mechanisms and sites of action remain uncertain. We investigated gabapentin-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal gabapentin reversed evoked mechanical hypersensitivity, produced conditioned place preference (CPP) and dopamine release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal gabapentin also significantly inhibited dorsal horn wide dynamic range (WDR) neuronal responses to a range of evoked stimuli in SNL rats. In contrast, gabapentin microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP and elicited NAc dopamine release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on WDR neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous gabapentin-induced CPP and NAc dopamine release but failed to block its inhibition of tactile allodynia. Gabapentin therefore can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from non-opioid analgesics, gabapentin requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of gabapentin’s analgesic effects in patients

Thoughts about the optimum data acquisition geometry and time resolution of monochromatic beam x-ray diffraction microscopy experiments

International audienceSo far, 3D X-ray diffraction microscopy (3DXRD) and X-ray diffraction contrast tomography (DCT) experiments have typically been performed in forward scattering geometry, the detector intercepting diffraction cones up to limited opening angles below 30°. The extension of the current synchrotron–based methodology towards 3D orientation mapping of deformed microstructures with down to (sub-)micrometer spatial resolution will require a reduction of the pixel and hence sample size by one order of magnitude. This in turn relaxes the need for high energy beams and opens interesting possibilities for new acquisition geometries, taking advantage of improved spatial resolution and strain sensitivity at high diffraction angles. First results obtained in this acquisition geometry will be discussed and a comparison to polychromatic micro-diffraction experiments is drawn

The Integrity of ACSR Full Tension Single-Stage Splice Connector at Higher Operation Temperature

Due to increases in power demand and limited investment in new infrastructure, existing overhead power transmission lines often need to operate at temperatures higher than those used for the original design criteria. This has led to the accelerated aging and degradation of splice connectors. It is manifested by the formation of hot-spots that have been revealed by infrared imaging during inspection. The implications of connector aging is two-fold: (1) significant increases in resistivity of the splice connector (i.e., less efficient transmission of electricity) and (2) significant reductions in the connector clamping strength, which could ultimately result in separation of the power transmission line at the joint. Therefore, the splice connector appears to be the weakest link in electric power transmission lines. This report presents a protocol for integrating analytical and experimental approaches to evaluate the integrity of full tension single-stage splice connector assemblies and the associated effective lifetime at high operating temperature

The role of single nucleotide polymorphisms in breast cancer metastasis

Our understanding of many aspects of cancer biology has been advanced through the use of modern genetics. These studies have already shown that germ line polymorphisms play a significant role in disease initiation and response to therapy. However, what is less well studied is the role of germ line polymorphisms in cancer progression. Studies in rodents indicate that differential susceptibility to cancer metastasis can be heritable; thus, the search for the genes that control cancer metastasis is underway. Although some provocative studies suggest potential candidates for metastasis regulating genes, the conclusive identification of a specific inherited genetic variant that alters metastatic potential awaits further studies

Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat

Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children

The Effects of Twitter Sentiment on Stock Price Returns

Social media are increasingly reflecting and influencing behavior of other complex systems. In this paper we investigate the relations between a well-know micro-blogging platform Twitter and financial markets. In particular, we consider, in a period of 15 months, the Twitter volume and sentiment about the 30 stock companies that form the Dow Jones Industrial Average (DJIA) index. We find a relatively low Pearson correlation and Granger causality between the corresponding time series over the entire time period. However, we find a significant dependence between the Twitter sentiment and abnormal returns during the peaks of Twitter volume. This is valid not only for the expected Twitter volume peaks (e.g., quarterly announcements), but also for peaks corresponding to less obvious events. We formalize the procedure by adapting the well-known "event study" from economics and finance to the analysis of Twitter data. The procedure allows to automatically identify events as Twitter volume peaks, to compute the prevailing sentiment (positive or negative) expressed in tweets at these peaks, and finally to apply the "event study" methodology to relate them to stock returns. We show that sentiment polarity of Twitter peaks implies the direction of cumulative abnormal returns. The amount of cumulative abnormal returns is relatively low (about 1-2%), but the dependence is statistically significant for several days after the events

Методические разработки для подготовки к практическим занятиям по оториноларингологии студентов 4-го курса стоматологического факультета ВГМУ

ГОРЛА БОЛЕЗНИНОСА БОЛЕЗНИОТОРИНОЛАРИНГОЛОГИЯУХА БОЛЕЗНИУЧЕБНО-МЕТОДИЧЕСКИЕ ПОСОБИЯВ методических разработках подробно изложены методики исследования ЛОР-органов, вопросы по анатомо-топографическим особенностям и физиологии уха, носа, глотки и гортани; представлены вопросы, касающиеся знаний и умений студентов по оториноларингологии, современные методы диагностики и лечения наиболее распространенных заболеваний ЛОР-органов; даны варианты тестов для определения уровня знаний, вопросы для самоподготовки к практическим занятиям

Assessing Internet addiction using the parsimonious Internet addiction components model - a preliminary study [forthcoming]

Internet usage has grown exponentially over the last decade. Research indicates that excessive Internet use can lead to symptoms associated with addiction. To date, assessment of potential Internet addiction has varied regarding populations studied and instruments used, making reliable prevalence estimations difficult. To overcome the present problems a preliminary study was conducted testing a parsimonious Internet addiction components model based on Griffiths’ addiction components (2005), including salience, mood modification, tolerance, withdrawal, conflict, and relapse. Two validated measures of Internet addiction were used (Compulsive Internet Use Scale [CIUS], Meerkerk et al., 2009, and Assessment for Internet and Computer Game Addiction Scale [AICA-S], Beutel et al., 2010) in two independent samples (ns = 3,105 and 2,257). The fit of the model was analysed using Confirmatory Factor Analysis. Results indicate that the Internet addiction components model fits the data in both samples well. The two sample/two instrument approach provides converging evidence concerning the degree to which the components model can organize the self-reported behavioural components of Internet addiction. Recommendations for future research include a more detailed assessment of tolerance as addiction component

Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link

There is substantial epidemiological evidence supporting the concept that respiratory syncytial virus (RSV) lower respiratory tract infection in infancy may be linked to the development of reactive airway disease (RAD) in childhood. However, much less is known concerning the mechanisms by which this self-limiting infection leads to airway dysfunction that persists long after the virus is cleared from the lungs. A better understanding of the RSV–RAD link may have important clinical implications, particularly because prevention of RSV lower respiratory tract infection may reduce the occurrence of RAD later in life. Among the mechanisms proposed to explain the chronic sequelae of RSV infection is the interaction between the subepithelial neural network of the airway mucosa and the cellular effectors of inflammatory and immune responses to the virus. The body of clinical literature linking RSV and RAD is reviewed herein, as are the cellular and molecular mechanisms of neuroimmune interactions and neural remodeling that may underlie this link, and the possibility that preventing the infection may result in a decreased incidence of its chronic sequelae

Digenean parasites of Chinese marine fishes: a list of species, hosts and geographical distribution

In the literature, 630 species of Digenea (Trematoda) have been reported from Chinese marine fishes. These belong to 209 genera and 35 families. The names of these species, along with their hosts, geographical distribution and records, are listed in this paper