Physiologically-based pharmacokinetic modeling for mirabegron: a multi-elimination pathway mediated by cytochrome P450 3A4, uridine 5'-diphosphate-glucuronosyltransferase 2B7, and butyrylcholinesterase

1. This was the first study to construct a physiologically-based pharmacokinetic (PBPK) model for mirabegron which incorporates the overall elimination pathways of metabolism by cytochrome P450 (CYP) 3A4, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B7, and butyrylcholinesterase (BChE) and renal excretion. The objective was to assess the risk of drug-drug interactions (DDIs) by estimating the contribution of each elimination pathway and simulating the magnitude of the DDIs with UGT2B7 inhibitors.

2. A PBPK model for mirabegron was constructed to reproduce the plasma concentration-time curves from a phase 1 study and the magnitude of the DDI with ketoconazole taking into account the overall elimination pathways. The PBPK model was subsequently verified using data from other DDI studies.

3. The constructed PBPK model estimated the contribution for each elimination pathway: 44% and 29% for CYP3A4 and UGT2B7 in the liver, 1.6% for UGT2B7 in the kidney, 3.2% for BChE in plasma, and 22% for renal excretion.

4. Co-administration of probenecid (an UGT2B7 inhibitor) or fluconazole (an UGT2B7 and CYP3A4 inhibitor) was predicted to increase area under the curve for mirabegron to 115% or 174%, respectively.

5. In conclusion, PBPK modeling and simulation revealed a low DDI risk for mirabegron following co-administration with BChE or UGT2B7 inhibitors.

     

Children’s participative citizenship within the context of integral care and daily life

The concept of participation was reviewed as a component of children's citizenship in order to promote a programme for Integral Development. A narrative revision of the literature was carried out as well as a group discussion was organized along with the staff of an Integral Care Programme, in order to identify notions of democracy and child citizenship related to care and rearing. Some elements that favoured the child participation and some parenting skills were identified. Among the elements that must be encouraged in children are: the development of emotional, cognitive and communicative skills and promotion of decision-making; among the parent skills development included are: sensitivity and responsivity; establishing routines and participation experiences. It is important to stand out that the identified elements to promote child participation and parental competences should be adapted to every specific cultural context.     

SNP interactions of Helicobacter pylori-related host genes PGC,PTPN11, IL1B,and TLR4 in susceptibility to gastric carcinogenesis

A series of host genes that respond to Helicobacter pylori (H. pylori) infection are involved in the process of gastric carcinogenesis. This study sought to examine interactions among polymorphisms of H. pylori-related genes PGC, PTPN11, TLR4, and IL1B and assess whether their interaction effects were modified by H. pylori infection. Thirteen polymorphisms of the aforementioned genes were genotyped by the Sequenom MassARRAY platform in 714 gastric cancer patients, 907 atrophic gastritis cases and 1276 healthy control subjects. When we considered the host genetic effects alone, gene–gene interactions consistently decreased the risks of gastric cancer and/or atrophic gastritis, including three two-way interactions: PGC rs6912200-PTPN11 rs12229892, PGC rs4711690-IL1B rs1143623 and PTPN11 rs12229892-IL1B rs1143623 and a three-way interaction: PGC rs4711690-PGC rs6912200-PTPN11 rs12229892. When the effect modification of H. pylori infection was evaluated, the cumulative effects of the aforementioned three-way interaction on atrophic gastritis susceptibility switched from being beneficial to being risky by the status of H. pylori infection. These data showed that SNP interactions among H. pylori-related genes PGC, PTPN11, and IL1B, are associated with susceptibility to gastric carcinogenesis. Moreover, we provided important hints of an effect modification by H. pylori infection on the cumulative effect of PGC and PTPN11 polymorphisms. Functional experiments and further independent large-scale studies especially in other ethnic populations are still needed to confirm our results.     

翻转课堂在护生法律法规教学中的应用

目的探讨翻转课堂教学模式在护生法律法规教学中的应用效果。方法试验组(n=44)借助微信小程序等平台,针对护生法律法规课程开展翻转课堂教学,对照组(n=43)则采取传统以教师为中心的授课法,在课程结束后通过课程考核成绩、自制满意度问卷和"护生自主学习能力评价调查表"比较教学效果和质量。结果试验组的课程考核成绩、自主学习能力和教学满意度均高于对照组,且差异有统计学意义(P<0.05)。结论运用翻转课堂教学模式开展护士法律法规教学,能够提高课程教学质量和护生教学体验,也有利于从不同维度培养护生的自主学习能力。     

The role of online videos in teaching procedural skills to post-graduate medical learners: A systematic narrative review

Abstract

Objective: Online videos are commonly used in medical education. The aim of this review was to investigate the role of online instructional videos in teaching procedural skills to postgraduate medical learners.

Methods: This systematic narrative review was conducted according to the PRISMA guidelines. MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, ERIC and Google Scholar were searched. Full texts that applied to online videos, postgraduate medical learners and procedural skills were included without language restrictions. The methodological quality of the studies was evaluated using a validated tool. A thematic analysis of the studies was carried out using a general inductive approach.

Results: A total of 785 articles were retrieved and the full text was reviewed for 66 articles that met the inclusion and exclusion criteria of the study. Twenty papers that were relevant to the role of online videos in postgraduate medical education of procedural skills were used for this review. They were heterogenous in the outcomes collected and the evidence was of variable quality. There was strong evidence for the use of online videos for procedural skill knowledge acquisition and retention. Online videos were used for various purposes, such as supervision, assessment, postoperative debriefing, providing feedback, and promoting reflection.

Conclusion: Online videos are a valuable educational tool especially for procedural skill knowledge acquisition and retention. Future research needs to be carried out on the appropriate use of platforms in disseminating and using online videos, identifying the factors surrounding the learners, video characteristics, and data protection.