Cannabidiol Mitigates Opioid Reward On Conditioned Place Preference In Mice

ABSTRACT This study sought to determine whether the cannabis constituent, cannabidiol (CBD), is able to attenuate morphine reward in the conditioned place preference (CPP) paradigm. Mice received IP injections of either saline or morphine and increasing doses of CBD that were paired with a distinct environment in the CPP apparatus. Morphine-produced place preference was dose-dependently blocked by CBD. Furthermore, none of the tested doses of CBD exhibited reward or aversion. The finding that CBD blocks opioid reward suggests CBD may be useful as an abuse deterrent, particularly in the setting of opioid use for pain management

Comparative Analysis of Requirements Change Prediction Models: Manual, Linguistic, and Neural Network

Requirement change propagation, if not managed, may lead to monetary losses or project failure. The a posteriori tracking of requirement dependencies is a well-established practice in project and change management. The identification of these dependencies often requires manual input by one or more individuals with intimate knowledge of the project. Moreover, the definition of these dependencies that help to predict requirement change is not currently found in the literature. This paper presents two industry case studies of predicting system requirement change propagation through three approaches: manually, linguistically, and bag-of-words. Dependencies are manually and automatically developed between requirements from textual data and computationally processed to develop surrogate models to predict change. Two types of relationship generation, manual keyword selection and part-of-speech tagging, are compared. Artificial neural networks are used to create surrogate models to predict change. These approaches are evaluated on three connectedness metrics: shortest path, path count, and maximum flow rate. The results are given in terms of search depth needed within a requirements document to identify the subsequent changes. The semi-automated approach yielded the most accurate results, requiring a search depth of 11 %, but sacrifices on automation. The fully automated approach is able to predict requirement change within a search depth of 15 % and offers the benefits of full minimal human input

Aging and aerobic fitness affect the contribution of noradrenergic sympathetic nerves to the rapid cutaneous vasodilator response to local heating

Sedentary aging results in a diminished rapid cutaneous vasodilator response to local heating. We investigated whether this diminished response was due to altered contributions of noradrenergic sympathetic nerves; assessing 1) the age-related decline and, 2) the effect of aerobic fitness. We measured skin blood flow (SkBF)(laser-Doppler flowmetry) in young (24±1 yr) and older (64±1 yr) endurance-trained and sedentary men (n=7 per group) at baseline and during 35 min of local skin heating to 42 °C at three forearm sites: 1) untreated; 2) bretylium tosylate (BT), preventing neurotransmitter release from noradrenergic sympathetic nerves; and 3) yohimbine and propranolol (YP), antagonising α- and β-adrenergic receptors. SkBF was converted to cutaneous vascular conductance (CVC) (SkBF/mean arterial pressure) and normalized to maximal CVC (%CVCmax) achieved by skin heating to 44 °C. Pharmacological agents were administered using microdialysis. In the young trained, the rapid vasodilator response was reduced at the BT and YP sites (P0.05) but treatment with BT did (P>0.05). Neither BT nor YP treatments affected the rapid vasodilator response in the older sedentary group (P>0.05). These data suggest that the age-related reduction in the rapid vasodilator response is due to an impairment of sympathetic-dependent mechanisms, which can be partly attenuated with habitual aerobic exercise. Rapid vasodilation involves noradrenergic neurotransmitters in young trained men, and non-adrenergic sympathetic cotransmitters (e.g., neuropeptide Y) in young sedentary and older trained men, possibly as a compensatory mechanism. Finally, in older sedentary men, the rapid vasodilation appears not to involve the sympathetic system

Effect of age on cutaneous vasomotor responses during local skin heating

This study examined the effect of ageing on the low-frequency oscillations (vasomotion) of skin blood flow in response to local heating (LH). Skin blood flow was assessed by laser-Doppler flowmetry on the forearm at rest (33 °C) and in response to LH of the skin to both 42 °C and 44 °C in 14 young (24 ± 1 years) and 14 older (64 ± 1 years) participants. Vasomotion was analyzed using a wavelet transform to investigate power of the frequency intervals associated with endothelial, neural, myogenic, respiratory, and cardiac activities of the laser-Doppler signal. Laser-Doppler flux increased in both groups with LH (both d > 1.8, p 1.2, p 0.9, p 0.7), myogenic (d = 0.3, p > 0.7), respiratory (d = 0.4, p > 0.6), and cardiac (d = 0.1, p > 0.7) frequency intervals. These data indicate that LH increases cutaneous endothelial and myogenic activity, while decreasing neural activity. Furthermore, ageing reduces the increase in cutaneous endothelial activity in response to LH

Polymorphism in killer cell immunoglobulin-like receptors and human leukocyte antigen-c and predisposition to preeclampsia in Ethiopian pregnant women population.

INTRODUCTION: Preeclampsia (PE) is a human specific pregnancy-related syndrome of unknown etiology that affects 2-8 % of pregnancies. Polymorphism in maternal Killer Cell Immunoglobulin-like Receptors (KIRs) and the ligand fetal Human Leukocyte Antigen-C (HLA-C) may predispose pregnant mothers for PE due to defective trophoblast invasion into the maternal decidua. Our study aimed to investigate the association between maternal KIR and fetal HLA-C polymorphism and PE in Ethiopian pregnant women. METHODS: We included a total of 288 (157 controls and 131 PE cases) in a case-controls study at Adama Regional Referral Hospital, Ethiopia. The KIR and HLA-C genotyping was done using traditional polymerase chain reaction on genomic DNA extracted form maternal venous and cord blood followed by 2% agarose gel electrophoresis. RESULTS: The statistical associations between variables were evaluated using Pearson's Chi-square test. P < 0.05, with 95 % confidence interval was considered statistically significant. A significant association was observed between the KIR2DS1 and PE, with a higher frequency (60.5 %) of the gene in the control group. Similarly, a significant association was observed between KIR AA genotype and PE, with a higher frequency (38.2 %) of this genotype in the PE group. Ethiopians share the same risk genotype for PE as seen in previous African and European studies, namely homozygosity of a maternal KIR AA genotype. However, Ethiopians differ from other East African populations by sharing the same protective KIR2DS1 gene as Europeans

Prolonged high-dose intravenous magnesium therapy for severe tetanus in the intensive care unit: a case series

<p>Abstract</p> <p>Introduction</p> <p>Tetanus rarely occurs in developed countries, but it can result in fatal complications including respiratory failure due to generalized muscle spasms. Magnesium infusion has been used to treat spasticity in tetanus, and its effectiveness is supported by several case reports and a recent randomized controlled trial.</p> <p>Case presentations</p> <p>Three Caucasian Greek men aged 30, 50 and 77 years old were diagnosed with tetanus and admitted to a general 12-bed intensive care unit in 2006 and 2007 for respiratory failure due to generalized spasticity. Intensive care unit treatment included antibiotics, hydration, enteral nutrition, early tracheostomy and mechanical ventilation. Intravenous magnesium therapy controlled spasticity without the need for additional muscle relaxants. Their medications were continued for up to 26 days, and adjusted as needed to control spasticity. Plasma magnesium levels, which were measured twice a day, remained in the 3 to 4.5 mmol/L range. We did not observe hemodynamic instability, arrhythmias or other complications related to magnesium therapy in these patients. All patients improved, came off mechanical ventilation, and were discharged from the intensive care unit in a stable condition.</p> <p>Conclusion</p> <p>In comparison with previous reports, our case series contributes the following meaningful additional information: intravenous magnesium therapy was used on patients already requiring mechanical ventilation and remained effective for up to 26 days (significantly longer than in previous reports) without significant toxicity in two patients. The overall outcome was good in all our patients. However, the optimal dose, optimal duration and maximum safe duration of intravenous magnesium therapy are unknown. Therefore, until more data on the safety and efficacy of magnesium therapy are available, its use should be limited to carefully selected tetanus cases.</p

All-sky Medium Energy Gamma-ray Observatory: Exploring the Extreme Multimessenger Universe

The All-sky Medium Energy Gamma-ray Observatory (AMEGO) is a probe class mission concept that will provide essential contributions to multimessenger astrophysics in the late 2020s and beyond. AMEGO combines high sensitivity in the 200 keV to 10 GeV energy range with a wide field of view, good spectral resolution, and polarization sensitivity. Therefore, AMEGO is key in the study of multimessenger astrophysical objects that have unique signatures in the gamma-ray regime, such as neutron star mergers, supernovae, and flaring active galactic nuclei. The order-of-magnitude improvement compared to previous MeV missions also enables discoveries of a wide range of phenomena whose energy output peaks in the relatively unexplored medium-energy gamma-ray band