Role of ABCB1 C3435T variant in response to antiepileptic drugs in epilepsy: a review

Over-expression of P-glycoprotein (P-gp), the encoded product of the ATP-binding cassette (ABC), sub-family B, member 1 (ABCB1/MDR1) gene, plays an important role in mediating multidrug resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation may in part explain inter-individual differences in phenotype-genotype relationships in the pharmacological response of epilepsy patients to AEDs. The synonymous C3435T polymorphism is one of the most common allelic variants in the ABCB1/MDR1 gene, proposed in the causation of refractory epilepsy. Many studies have shown the relationship between C3435T polymorphism and refractoriness to AEDs in epilepsy. However, there is controversy between the findings of various studies, that is, whether ABCB1/MDR1 C3435T gene polymorphism is associated with response to AEDs in epilepsy patients. This review provides a background and discusses the results of investigations on possible confounding factors affecting the interpretation and implementation of association studies in this area

Antecedents of consumer trust in mobile payment adoption

This study empirically examines the role of consumer trust and its antecedents in determining consumers’ intention to adopt mobile payment. This research proposes that consumers’ willingness to adopt mobile payment depends on their assessment of the trustworthiness of mobile service provider and vendor, their assessment of the functional reliability of mobile payment systems as well as their general disposition to trust and their cultural background, in particular, uncertainty avoidance. Data were gathered from 302 participants in Auckland, New Zealand. Results show that all five sets of trust antecedents influence the development of trust and trust is an important predictor of intention to adopt mobile payment. Both theoretical and practical implications are discussed

A REVIEW OF CINNAMON AS A POTENT ANTICANCER DRUG

ABSTRACTCinnamon is one of the most popular and oldest spices. Several recent studies have found that cinnamon also has anticancer activity. The present workhas reported the antineoplastic potential of the spice cinnamon in cancer. Collectively, these data suggest that cinnamon could be proposed as a potentanticancer drug. The bibliographic investigation was carried out during January 2004-December 2014 by analyzing journals and peer-reviewedpapers from the last decades. Peer-reviewed articles were indexed by Scopus, PubMed, and Google scholar. Only relevant studies published in Englishwere considered. There were 24 articles that reported the cytotoxic activity of cinnamon on all culture cell lines. About 8 species of Cinnamomum havebeen isolated with their active compounds for cancer cell lines. Based on the reviews of those articles, we conclude that cinnamon has the potentialto be further developed as an anticancer agent. In further development, however, not only the research for investigating the anticancer activities, butalso research for investigating the safety of cinnamon to the normal cell need to be performed.Keywords: Review, Cinnamon, Anticancer, Cinnamomum species, Cell lines

GAS CHROMATOGRAPH-MASS SPECTROMETER ANALYSIS AND ACUTE ORAL TOXICITY OF CINNAMOMUM BURMANNII., NESS EX BL. ESSENTIAL OIL

ABSTRACTObjective: Cinnamomum burmannii Nees Ex Bl. essential oil has cytotoxic effect on a lot of cancer cell lines. An investigation was carried out to analyzethe possible chemical components from C. burmannii essential oil and evaluate its acute toxicity, before an effective formulation of C. burmanniiessential oil as anticancer drugs.Methods: This study was analyzed chemical components from C. burmannii essential oil by gas chromatograph-mass spectrometer (GC-MS) andevaluated the acute oral toxicities of C. burmannii essential oil in strain Balb/C mice. Results: This analysis revealed that C. burmannii essential oil contains the active compound cinnamaldehyde (71.814%), trans-cinnamyl acetate(11.09%), coumarin (3.41%), and cineol (1.77%). Acute oral toxicity of C. burmannii essential oil with lethal dose 50 3679.11 mg/kg BW.Conclusion: C. burmannii essential oil contains the active compound cinnamaldehyde, trans-cinnamyl acetate, coumarin and cineol. Acute oral toxicityconclusively indicates C. burmannii essential oil includes category 5 practically non-toxic.Keywords: Gas chromatograph-mass spectrometer, Cinnamomum burmannii, Essential oil, Acute toxicity

Use of an alternative method to evaluate erythema severity in a clinical trial: difference in vehicle response with evaluation of baseline and postdose photographs for effect of oxymetazoline cream 1·0% for persistent erythema of rosacea in a phase IV study.

BackgroundOnce-daily topical oxymetazoline cream 1·0% significantly reduced persistent facial erythema of rosacea in trials requiring live, static patient assessments.ObjectivesTo evaluate critically the methodology of clinical trials that require live, static patient assessments by determining whether assessment of erythema is different when reference to the baseline photograph is allowed.MethodsIn two identically designed, randomized, phase III trials, adults with persistent facial erythema of rosacea applied oxymetazoline or vehicle once daily. This phase IV study evaluated standardized digital facial photographs from the phase III trials to record ≥ 1-grade Clinician Erythema Assessment (CEA) improvement at 1, 3, 6, 9 and 12 h postdose.ResultsAmong 835 patients (oxymetazoline n = 415, vehicle n = 420), significantly greater proportions of patients treated with oxymetazoline vs. vehicle achieved ≥ 1-grade CEA improvement. For the comparison between phase IV study results and the original phase III analysis, when reference to baseline photographs was allowed while evaluating post-treatment photographs, the results for oxymetazoline were similar to results of the phase III trials (up to 85.7%), but a significantly lower proportion of vehicle recipients achieved ≥ 1-grade CEA improvement (up to 29.7% [phase 4] vs. 52.3% [phase 3]; P<0.001). In the phase IV study, up to 80·2% of patients treated with oxymetazoline achieved at least moderate erythema improvement vs. up to 22·9% of patients treated with vehicle. The association between patients' satisfaction with facial skin redness and percentage of erythema improvement was statistically significant.ConclusionsAssessment of study photographs, with comparison to baseline, confirmed significant erythema reduction with oxymetazoline on the first day of application. Compared with the phase III trial results, significantly fewer vehicle recipients attained ≥ 1-grade CEA improvement, suggesting a mitigated vehicle effect. This methodology may improve the accuracy of clinical trials evaluating erythema severity

Toxicological evaluation of precocene II isolated from Ageratum conyzoides L. (Asteraceae) in Sprague Dawley rats

Precocene II (6,7-dimethoxy-2,2-dimethyl-2-chromene) was the main constituent isolated from Ageratum conyzoides L. and reportedly possessed antifungal activity. The study investigated the isolation,purification and toxicological effects of precocene II from A. conyzoides in Sprague Dawley rats. Precocene II was isolated from the petroleum ether fraction of the plant and the structure was determined by  1H-,13C-,DEPT-NMR and MS spectral techniques. Three groups of eight rats per group were used for the study. While groups B and C were respectively administered with 25 and 50 mg/kg of precocene II in 0.25% CMC-Na for 11 days by gastric intubation, group A was administered with 0.25% CMC-Na and served as the control group. After the last treatment, animals were fasted overnight and on the 12th day, they were injected intravenously with 0.2 ml/kg body weight of phenobarbital. Animalswere subsequently dissected from the abdominal region; blood was collected from the pulmonary vein into EDTA anti-coagulated and non anti-coagulated tubes. The liver, kidney and spleen tissues wereextracted into separate bottles for histopathological examinations. Results from hematological study indicated that the white blood cell (WBC), red blood cell (RBC), plateletcrit (PCT) and mean corpuscular hemoglobin count (MCHC) were significantly higher across the treated group s. Biochemical result showed that serum glucose level was significantly reduced in the treated groups. No apparent damage was noticed in the liver, kidney and spleen tissues. The result therefore suggests that precocene II possesses hypoglycemic property and could alter some hematopoietic elements but was not toxic to the liver, kidney and spleen tissues

Bigger Buffer k-d Trees on Multi-Many-Core Systems

A buffer k-d tree is a k-d tree variant for massively-parallel nearest neighbor search. While providing valuable speed-ups on modern many-core devices in case both a large number of reference and query points are given, buffer k-d trees are limited by the amount of points that can fit on a single device. In this work, we show how to modify the original data structure and the associated workflow to make the overall approach capable of dealing with massive data sets. We further provide a simple yet efficient way of using multiple devices given in a single workstation. The applicability of the modified framework is demonstrated in the context of astronomy, a field that is faced with huge amounts of data

IL11 stimulates ERK/P90RSK to inhibit LKB1/AMPK and activate mTOR initiating a mesenchymal program in stromal, epithelial, and cancer cells

IL11 initiates fibroblast activation but also causes epithelial cell dysfunction. The mechanisms underlying these processes are not known. We report that IL11-stimulated ERK/P90RSK activity causes the phosphorylation of LKB1 at S325 and S428, leading to its inactivation. This inhibits AMPK and activates mTOR across cell types. In stromal cells, IL11-stimulated ERK activity inhibits LKB1/AMPK which is associated with mTOR activation, ⍺SMA expression, and myofibroblast transformation. In hepatocytes and epithelial cells, IL11/ERK activity inhibits LKB1/AMPK leading to mTOR activation, SNAI1 expression, and cell dysfunction. Across cells, IL11-induced phenotypes were inhibited by metformin stimulated AMPK activation. In mice, genetic or pharmacologic manipulation of IL11 activity revealed a critical role of IL11/ERK signaling for LKB1/AMPK inhibition and mTOR activation in fatty liver disease. These data identify the IL11/mTOR axis as a signaling commonality in stromal, epithelial, and cancer cells and reveal a shared IL11-driven mesenchymal program across cell types

Midlatitude Plasma Bubbles Over China and Adjacent Areas During a Magnetic Storm on 8 September 2017

This paper presents observations of postsunset super plasma bubbles over China and adjacent areas during the second main phase of a storm on 8 September 2017. The signatures of the plasma bubbles can be seen or deduced from (1) deep field‐aligned total electron content depletions embedded in regional ionospheric maps derived from dense Global Navigation Satellite System networks, (2) significant equatorial and midlatitudinal plasma bite‐outs in electron density measurements on board Swarm satellites, and (3) enhancements of ionosonde virtual height and scintillation in local evening associated with strong southward interplanetary magnetic field. The bubbles/depletions covered a broad area mainly within 20°–45°N and 80°–110°E with bifurcated structures and persisted for nearly 5 hr (∼13–18 UT). One prominent feature is that the bubbles extended remarkably along the magnetic field lines in the form of depleted flux tubes, reaching up to midlatitude of around 50°N (magnetic latitude: 45.5°N) that maps to an altitude of 6,600 km over the magnetic equator. The maximum upward drift speed of the bubbles over the magnetic equator was about 700 m/s and gradually decreased with altitude and time. The possible triggering mechanism of the plasma bubbles was estimated to be storm time eastward prompt penetration electric field, while the traveling ionospheric disturbance could play a role in facilitating the latitudinal extension of the depletions.Key PointsPostsunset midlatitude plasma bubbles were observed over China and adjacent areas using GNSS TEC, Swarm Ne, and ionosonde dataThe plasma bubbles were triggered by PPEF and TID in equatorial regions and extended along the magnetic field lines to 50°N (45.5 MLAT)Plasma bubbles might reach an altitude of 6,600 km over the magnetic equator with the upper limit of upward drift speed being around 700 m/sPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143723/1/swe20573.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143723/2/swe20573_am.pd