The nicotine + alcohol interoceptive drug state: contribution of the components and effects of varenicline in rats

Nicotine and alcohol co-use is highly prevalent, and as such, individuals experience the interoceptive effects of both substances together. Therefore, examining sensitivity to a compound nicotine and alcohol (N+A) interoceptive cue is critical to broaden our understanding of mechanisms that may contribute to nicotine and alcohol co-use

Platelet-Rich Plasma Injection With Percutaneous Needling for Recalcitrant Lateral Epicondylitis: Comparison of Tenotomy and Fenestration Techniques.

Background: Recalcitrant lateral epicondylitis (LE) is a common debilitating condition, with numerous treatment options of varying success. An injection of platelet-rich plasma (PRP) has been shown to improve LE, although it is unclear whether the method of needling used in conjunction with a PRP injection is of clinical importance. Purpose: To determine whether percutaneous needle tenotomy is superior to percutaneous needle fenestration when each is combined with a PRP injection for the treatment of recalcitrant LE. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 93 patients with recalcitrant LE were treated with a PRP injection and percutaneous needle fenestration (n = 45) or percutaneous needle tenotomy (n = 48) over a 5-year study interval. Preoperative patient data, including visual analog scale for pain (VAS-P), Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), and Patient-Rated Tennis Elbow Evaluation (PRTEE) scores and grip strength, were obtained from a chart review and compared with postoperative values obtained prospectively. Secondary outcomes included the incidence of complications, need for additional interventions, return to work, and patient satisfaction. Results: At a mean follow-up of 40 months, significant improvements in VAS-P (mean, -6.1; 95% CI, -6.8 to -5.5; P \u3c .0001), QuickDASH (mean, -46; 95% CI, -52 to -40; P \u3c .0001), and PRTEE (mean, -57; 95% CI, -64 to -50; P \u3c .0001) scores and grip strength (mean, +6.1 kg; 95% CI, 4.9 to 7.3; P \u3c .0001) were observed across the entire study cohort, with no significant differences noted between the fenestration and tenotomy groups. Nine of 45 patients (22%) underwent additional procedures to treat recurrent symptoms in the fenestration group compared with 5 of 48 patients (10%) in the tenotomy group (P = .05). No complications occurred in any patients, and no patients expressed dissatisfaction with their treatment course. Conclusion: A PRP injection with concomitant percutaneous needling is an effective treatment for recalcitrant LE, with sustained improvements in pain, strength, and function demonstrated at a mean follow-up of longer than 3 years. Although the method of concomitant needling does not appear to have a significant effect on treatment outcomes, more aggressive needle tenotomy is less likely to require conversion to open tenotomy than needle fenestration in the short term to midterm

Modulation of sensitivity to alcohol by cortical and thalamic brain regions

The nucleus accumbens core (AcbC) is a key brain region known to regulate the discriminative stimulus/interoceptive effects of alcohol. As such, the goal of the present work was to identify AcbC projection regions that may also modulate sensitivity to alcohol. Accordingly, AcbC afferent projections were identified in behaviorally naïve rats using a retrograde tracer which led to the focus on the medial prefrontal cortex (mPFC), insular cortex (IC) and rhomboid thalamic nucleus (Rh). Next, to examine the possible role of these brain regions in modulating sensitivity to alcohol, neuronal response to alcohol in rats trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water was examined using a two-lever drug discrimination task. As such, rats were administered water or alcohol (1g/kg, IG) and brain tissue was processed for c-Fos immunoreactivity (IR), a marker of neuronal activity. Alcohol decreased c-Fos IR in the mPFC, IC, Rh, and AcbC. Lastly, site-specific pharmacological inactivation with muscimol+baclofen (GABAA agonist+GABAB agonist) was used to determine the functional role of the mPFC, IC and Rh in modulating the interoceptive effects of alcohol in rats trained to discriminate alcohol (1 g/kg, IG) vs. water. mPFC inactivation resulted in full substitution for the alcohol training dose, and IC and Rh inactivation produced partial alcohol-like effects, demonstrating the importance of these regions, with known projections to the AcbC, in modulating sensitivity to alcohol. Together, these data demonstrate a site of action of alcohol and the recruitment of cortical/thalamic regions in modulating sensitivity to the interoceptive effects of alcohol

Gabapentin potentiates sensitivity to the interoceptive effects of alcohol and increases alcohol self-administration in rats

Gabapentin, a drug used in the treatment of epileptic seizures and neuropathic pain, has shown efficacy in the treatment of alcohol dependence. Moreover, given that gabapentin is used in the general population (e.g., non-dependent individuals, social drinkers), we sought to utilize preclinical assessments to examine the effects of gabapentin on sensitivity to moderate alcohol doses and alcohol self-administration in rats with a history of moderate drinking. To this end, we assessed whether gabapentin (0, 10, 30, 120 mg/kg, IG) pretreatment alters sensitivity to experimenter- and self-administered alcohol, and whether gabapentin alone has alcohol-like discriminative stimulus effects in rats trained to discriminate a moderate alcohol dose (1 g/kg, IG) vs. water. Second, we assessed whether gabapentin (0, 10, 30, 60 mg/kg, IG) would alter alcohol self-administration in rats with a history of moderate alcohol consumption. Gabapentin pretreatment potentiated the interoceptive effects of both experimenter-administered and self-administered alcohol in discrimination-trained rats. Additionally, the highest gabapentin doses tested (30 and 120 mg/kg) were found to have partial alcohol-like discriminative stimulus effects when administered alone (e.g., without alcohol). In the self-administration trained rats, gabapentin pretreatment (60 mg/kg) resulted in an escalation in alcohol self-administration. Given the importance of interoceptive drug cues in priming and maintaining self-administration, these data define a specific behavioral mechanism (i.e., potentiation of alcohol effects) by which gabapentin may increase alcohol self-administration in non-dependent populations

An X-Ray Study of the Supernova Remnant G290.1-0.8

G290.1-0.8 (MSH 11-61A) is a supernova remnant (SNR) whose X-ray morphology is centrally bright. However, unlike the class of X-ray composite SNRs whose centers are dominated by nonthermal emission, presumably driven by a central pulsar, we show that the X-ray emission from G290.1-0.8 is thermal in nature, placing the remnant in an emerging class which includes such remnants as W44, W28, 3C391, and others. The evolutionary sequence which leads to such X-ray properties is not well understood. Here we investigate two scenarios for such emission: evolution in a cloudy interstellar medium, and early-stage evolution of a remnant into the radiative phase, including the effects of thermal conduction. We construct models for these scenarios in an attempt to reproduce the observed center-filled X-ray properties of G290.1-0.8, and we derive the associated age, energy, and ambient density conditions implied by the models. We find that for reasonable values of the explosion energy, the remnant age is of order (1 - 2) x 10^{4} yr. This places a fairly strong constraint on any association between G290.1-0.8 and PSR J1105-610, which would require an anomalously large velocity for the pulsar.Comment: 7 pages, 7 figures, ApJ, accepte

Comparative analysis of classic brain component sizes in relation to flightiness in birds

Increased encephalization has been linked to a range of behavioural traits and scenarios. However, studies of whole brain size in this context have been criticised for ignoring the role of specific brain areas in controlling behaviour. In birds, the response to potential threats is one such behaviour that may relate to the way in which the brain processes sensory information. We used a phylogenetic generalised least squares (PGLS) analyses, based on five different phylogenetic hypotheses, to analyse the relationship of relative sizes of whole brain and brain components with Flight-Initiation Distance (FID), the distance at which birds flee from an approaching human, for 41 bird species. Starting distance (the distance at which an approach to a bird commences), body mass and eye size have elsewhere been shown to be positively associated with FID, and consequently were included as covariates in our analysis. Starting distance and body mass were by far the strongest predictors of FID. Of all brain components, cerebellum size had the strongest predictor weight and was negatively associated with FID but the confidence intervals on the average estimate included zero and the overall predictor weight was low. Models featuring individual brain components were generally more strongly weighted than models featuring whole brain size. The PGLS analyses estimated there to be no phylogenetic signal in the regression models, and hence produced results equivalent to ordinary least squares regression analysis. However analyses that assumed strong phylogenetic signal produced substantially different results with each phylogeny, and overall suggest a negative relationship between forebrain size and FID. Our analyses suggest that the evolutionary assumptions of the comparative analysis, and consideration of starting distance make a profound difference to the interpretation of the effect of brain components on FID in birds

New Evidence for Efficient Collisionless Heating of Electrons at the Reverse Shock of a Young Supernova Remnant

Although collisionless shocks are ubiquitous in astrophysics, certain key aspects of them are not well understood. In particular, the process known as collisionless electron heating, whereby electrons are rapidly energized at the shock front, is one of the main open issues in shock physics. Here we present the first clear evidence for efficient collisionless electron heating at the reverse shock of Tycho's supernova remnant (SNR), revealed by Fe-K diagnostics using high-quality X-ray data obtained by the Suzaku satellite. We detect K-beta (3p->1s) fluorescence emission from low-ionization Fe ejecta excited by energetic thermal electrons at the reverse shock front, which peaks at a smaller radius than Fe K-alpha (2p->1s) emission dominated by a relatively highly-ionized component. Comparison with our hydrodynamical simulations implies instantaneous electron heating to a temperature 1000 times higher than expected from Coulomb collisions alone. The unique environment of the reverse shock, which is propagating with a high Mach number into rarefied ejecta with a low magnetic field strength, puts strong constraints on the physical mechanism responsible for this heating, and favors a cross-shock potential created by charge deflection at the shock front. Our sensitive observation also reveals that the reverse shock radius of this SNR is about 10% smaller than the previous measurement using the Fe K-alpha morphology from the Chandra observations. Since strong Fe K-beta fluorescence is expected only from low-ionization plasma where Fe ions still have many 3p electrons, this feature is key to diagnosing the plasma state and distribution of the immediate postshock ejecta in a young SNR.Comment: 7 pages, 9 figures, resubmitted to ApJ with minor changes following the referee repor