Lyhneblaabjerg8076
Domestic animals show considerable genetic diversity. Previous studies suggested that animal phenotypes were affected by miRNA-mRNA interplay, but these studies focused mainly on the analysis of one or several miRNA-mRNA interactions. However, in this study, we investigated miRNA-mRNA and miRNA-lncRNA interactions on a genomic scale using miranda and targetscan algorithms. There has been strong directional artificial selection practiced during the domestication of animals. Thus, we investigated SNPs that were located in miRNAs and miRNA binding sites and found that several SNPs located in 3'-UTRs of mRNAs had the potential to affect miRNA-mRNA interactions. In addition, a database, named miRBond, was developed to provide visualization, analysis and downloading of the resulting datasets. Our results open the way to further experimental verification of miRNA-mRNA and miRNA-lncRNA interactions as well as the influence of SNPs upon such interplay.Ophthalmic diseases include both those analogous to systemic diseases (eg, inflammation, infection, neuronal degeneration) and not analogous (eg, cataract, myopia). Many anterior segment diseases are treated pharmacologically through eye drops, which have an implied therapeutic index of local therapy. Unlike oral dosage forms administered for systemic diseases, eyedrops require patients not only to adhere to treatment, but to be able to accurately perform-ie, instill drops correctly. Anatomical and physiological barriers make topical delivery to the anterior chamber challenging-in some cases more challenging than absorption through the skin, nasal passages, or gut. Treatment of the posterior segment (eg, vitreous, retina, choroid, and optic nerve) is more challenging due to additional barriers. Recently, intravitreal injections have become a standard of care with biologics for the treatment of macular degeneration and other diseases. Although the eye has esterases, hydroxylases, and transporters, it has relatively little CYP450 enzymes. Because it is challenging to obtain drug concentrations at the target site, ocular clinical pharmacokinetics, and thus pharmacokinetic-pharmacodynamic interactions, are rarely available. Ophthalmic pharmaceuticals require consideration of solubility, physiological pH, and osmolarity, as well as sterility and stability, which in turn requires optimal pharmaceutics. Although applied locally, ocular medications may be absorbed systemically, which results in morbidity and mortality (eg, systemic hypotension, bronchospasm, and bradycardia).Aconitine (AC), benzoylaconine (BAC), and aconine (ACN) are three representative alkaloids in Aconitum tubers. Knowing that the drug disposal process in vivo is closely related to the toxicity and efficacy of a drug, it is important to classify the disposal properties of these alkaloids. In this study, the pharmacokinetics of the three alkaloids was investigated. The results showed that the three alkaloids could be quickly absorbed, especially BAC, whose Tmax was 0.31 ± 0.17 h. Their Cmax was 10.99, 3.99, and 4.29 ng·mL(-1) respectively, indicating that AC had better absorption than BAC and ACN. Subsequently, we further investigated their absorption mechanism using the Caco-2 cell monolayer model in vitro. The results showed that they were poorly absorbed, and the absorption of AC and BAC was inhibited by P-gp, while the absorption of ACN was in a form of passive diffusion. The t1/2 of AC, BAC and ACN was 1.41, 9.49, and 3.32 h, respectively, indicating that the metabolic or excretion rate of AC was quicker than that of BAC and ACN. Therefore, their metabolic stability was further investigated by using rat liver microsomes in vitro, which showed that AC was easier to be metabolized than BAC and ACN. The excretion experiments showed that AC and ACN were primarily excreted in urine, while BAC was excreted in faeces. In addition, the results of tissue distribution experiments showed that the three alkaloids distributed throughout all the organs, although the distribution rate of AC was slower than that of BAC and ACN. Copyright © 2015 John Wiley & Sons, Ltd.Mallory-type photocyclization involves a series of photoreactions of stilbenes, o-terphenyls and related derivatives, which undergo intramolecular cyclization via dihydrophenanthrene intermediates. In typical Mallory photocyclizations, oxidants are usually needed to produce the final phenanthrene-containing product. In the research described here, appropriately fluorinated stilbenes and o-terphenyls undergo ring closure and HF is eliminated. This photocyclodehydrofluorination (PCDHF) reaction is very useful to produce a wide range of selectively fluorinated polynuclear aromatic hydrocarbons that possess a phenanthrene (or heterocyclic analogue of phenanthrene) substructure. These fluorinated products are of great interest in various aspects of the materials science.Simplifying the therapeutic regimen of liver transplantation (LT) recipients may help prevent acute rejection and graft failure. The present study aimed to evaluate the efficacy and safety of conversion from twice-daily tacrolimus to once-daily extended-release tacrolimus under concurrent mycophenolate mofetil therapy in stable LT recipients. This randomized, prospective, controlled study included 91 patients who underwent LTs with at least 1 year of posttransplant follow-up. Conversion was made on a 1 mg to 1 mg basis. No incidences of biopsy-proven acute rejection, graft failure, or death were reported in either group at 24 weeks. Median serum tacrolimus level of the study group was 20% less than that of the control group at 8 weeks. However, no significant differences regarding biochemical indicators of liver function or serum creatinine levels were observed between the 2 groups. Adverse event (AE) profiles were similar for both groups, with comparable incidences of AEs and serious AEs. No significant differences regarding efficacy or safety were observed between the once-daily tacrolimus and twice-daily tacrolimus groups of stable LT recipients. In conclusion, our study suggests that tacrolimus can be safely converted from a twice-daily regimen to a once-daily regimen in stable LT recipients.
Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner.
Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states.
Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P < 0.003, n = 14), and this was voltage dependent (P < 0.001).
Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS.
Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS.
Cricopharyngeal dysfunction may lead to severe dysphagia and aspiration. The objective of this systematic review was to evaluate the existing studies on the effectiveness of myotomy, dilatation, and botulinum toxin (BoT) injection in the management of cricopharyngeal dysphagia.
PubMed and Web of Science databases were searched to identify eligible studies by using the terms "cricopharyngeal dysfunction," "cricopharyngeal myotomy," "cricopharyngeal botox," "cricopharyngeal dilation," and their combinations from 1990 to 2013. This was supplemented by hand-searching relevant articles. Eligible articles were independently assessed for quality by two authors. Statistical analysis was performed.
The database search revealed 567 articles. Thirty-two articles met eligibility criteria and were further evaluated. The reported success rates of BoT injections was between 43% and 100% (mean = 76%), dilation 58% and 100% (mean = 81%), and myotomy 25% and 100% (mean = 75%). In logistic regression analysis of the patient-weighted averages, the 78% success rate with myotomy was significantly higher than the 69% success rate with BoT injections (P = .042), whereas the intermediate success rate of 73% with dilation was not significantly different from that of either myotomy (P = .37) or BoT (P = .42). There was a statistically significant difference between endoscopic and open myotomy success rates (P = .0025). Endoscopic myotomy had a higher success rate, with a 2.2 odds ratio.
The success rate of myotomy is significantly higher than the success rate of BoT injections in cricopharyngeal dysfunction. Moreover, endoscopic myotomy was found to have a higher success rate compared to open myotomy.
The success rate of myotomy is significantly higher than the success rate of BoT injections in cricopharyngeal dysfunction. Moreover, endoscopic myotomy was found to have a higher success rate compared to open myotomy.
Monitoring trends of alcohol-attributable mortality is an integral part of the global strategy to reduce the harmful use of alcohol. However, mortality estimates based on different age ranges come to different conclusions. This study examined the impact of including different age ranges in terms of directions of trends of alcohol-attributable mortality during 14 years in Switzerland.
Alcohol-attributable mortality was estimated at four time-points between 1997 and 2011 using the Global Burden of Disease 2010 methodology. Estimates were obtained for two age groups 15-64 years and the total adult population (15 years and older).
Alcohol-attributable mortality among 15-64-year-olds decreased [1997 1334 deaths, confidence interval (CI) = 1237-1432; 2011 1019 deaths, CI = 964-1073; trend per year odds ratio (OR) = 0.99, P < 0.001]. In contrast, alcohol-attributable mortality among those 65 and older increased in the same time-period (1997 581 deaths, CI = -196 to 1357; 2011 1664 deaths, CI = 957-2372; OR were influenced heavily by changes in the mixture of deaths across cardiovascular diseases. Trends for alcohol-attributable mortality and cross-country comparisons should be reported separately for 15-64 and 65+ year-olds.
