Comparative studies on the binding site of anesthetics to GABA a receptors using in silico docking methods

Although the GABAA receptor(GABAAR)has been proposed as the main action site for sevoflurane,isoflurane,halothane,enflurane,propofol,and benzodiazepines(BZDs),binding of these anesthetics with high-resolution structures of the GABAAR have been rarely examined by comparative docking analyses.Moreover,various combinations of ligands on more GABAARs with various subtypes need to be analyzed to understand the elaborate action mechanism of GABAARs better because some GABAA ligands showed specificity toward the distinct subtypes of the GABAAR.Methods:We performed in silico docking analysis to compare the binding modes of sevoflurane,isoflurane,halothane,enflurane,propofol,and BZDs to the GABAAR based on one of the most recently provided 3D structures.We performed the docking analysis and the affinity-based ranking of the binding sites.Results:Our docking studies revealed that isoflurane,halothane,and enflurane docked in an extracellular domain(ECD)on GABAARs,in contrast to sevoflurane.Conclusion:Our results supported a multi-site mechanism for the allosteric modulation of propofol.Propofol was bound to the pore or favored various subsites in the transmembrane domain(TMD).Our result confirmed that different chemically related BZD ligands interact via distinct binding modes rather than by using a common binding mode,as previously suggested.

A critical readability and quality analysis of internet-based patient information on neck dissections

Objective:Patients are increasingly turning to the Internet as a source of healthcare information.Given that neck dissection is a common procedure within the field of Otolaryngology-Head and Neck Surgery,the aim of this study was to evaluate the quality and readability of online patient education materials on neck dissection.Methods:A Google search was performed using the term"neck dissection."The first 10 pages of a Google search using the term"neck dissection"were analyzed.The DISCERN instrument was used to assess quality of information.Readability was calculated using the Flesch-Reading Ease,Flesch-Kincaid Grade Level,Gunning-Fog Index,Coleman-Liau Index,and Simple Measure of Gobbledygook Index.Results:Thirty-one online patient education materials were included.Fifty-five percent(n=17)of results originated from academic institutions or hospitals.The mean Flesch-Reading Ease score was 61.2±11.9.Fifty-two percent(n=16)of patient education materials had Flesch-Reading Ease scores above the recommended score of 65.The average reading grade level was 10.5±2.1.The average total DISCERN score was 43.6±10.1.Only 26%of patient education materials(PEMs)had DISCERN scores corresponding to a"good quality"rating.There was a significant positive correlation between DISCERN scores and both Flesch-Reading Ease scores and average reading grade level.Conclusions:The majority of patient education materials were written above the recommended sixth-grade reading level and the quality of online information pertaining to neck dissections was found to be suboptimal.This research highlights the need for patient education materials regarding neck dissection that are high quality and easily understandable by patients.