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1.
Br J Clin Pharmacol ; 2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38520277

ABSTRACT

AIMS: This randomized controlled pilot study aimed to assess the differences in the frequency, type and severity of prescribing errors made by medical students when assessed in an electronic (e-)prescribing system compared to a traditional prescribing method (e.g., typing out a prescription). METHODS: Fourth year medical students in the period of 1 November to 31 July 2023, were asked to participate in this single-centre prospective, randomized, controlled intervention study. Participants performed a prescribing assessment in either an e-prescribing system (intervention group) or in a more traditional prescribing platform (control group). The prescriptions were checked for errors, graded and categorized. Differences in prescribing errors, error categories and severity were analysed. RESULTS: Out of 334 students, 84 participated in the study. Nearly all participants (98.8%) made 1 or more prescribing errors, primarily involving inadequate information errors. In the intervention group, more participants made prescribing errors involving the prescribed amount (71.4 vs. 19.0%; P < .01), but fewer involving administrative errors (2.4 vs. 19.0%; P = .03). Prescribing-method-specific errors were identified in 4.8 and 40.5% of the intervention and control group, respectively, with significant differences in overlapping errors as well. CONCLUSION: This pilot study shows the importance of training e-prescribing competencies in medical curricula, in addition to traditional prescribing methods. It identifies prescribing-method-specific prescribing errors and emphasizes the need for further research to define e-prescribing competencies. Additionally, the need for an accessible real-life-like e-prescribing environment tailored to educators and students is essential for effective learning and incorporation of e-prescribing into medical curricula.

2.
J Biol Chem ; 293(52): 19942-19956, 2018 12 28.
Article in English | MEDLINE | ID: mdl-30355733

ABSTRACT

We previously reported that transcription of the human IL1B gene, encoding the proinflammatory cytokine interleukin 1ß, depends on long-distance chromatin looping that is stabilized by a mutual interaction between the DNA-binding domains (DBDs) of two transcription factors: Spi1 proto-oncogene at the promoter and CCAAT enhancer-binding protein (C/EBPß) at a far-upstream enhancer. We have also reported that the C-terminal tail sequence beyond the C/EBPß leucine zipper is critical for its association with Spi1 via an exposed residue (Arg-232) located within a pocket at one end of the Spi1 DNA-recognition helix. Here, combining in vitro interaction studies with computational docking and molecular dynamics of existing X-ray structures for the Spi1 and C/EBPß DBDs, along with the C/EBPß C-terminal tail sequence, we found that the tail sequence is intimately associated with Arg-232 of Spi1. The Arg-232 pocket was computationally screened for small-molecule binding aimed at IL1B transcription inhibition, yielding l-arginine, a known anti-inflammatory amino acid, revealing a potential for disrupting the C/EBPß-Spi1 interaction. As evaluated by ChIP, cultured lipopolysaccharide (LPS)-activated THP-1 cells incubated with l-arginine had significantly decreased IL1B transcription and reduced C/EBPß's association with Spi1 on the IL1B promoter. No significant change was observed in direct binding of either Spi1 or C/EBPß to cognate DNA and in transcription of the C/EBPß-dependent IL6 gene in the same cells. These results support the notion that disordered sequences extending from a leucine zipper can mediate protein-protein interactions and can serve as druggable targets for regulating gene promoter activity.


Subject(s)
CCAAT-Enhancer-Binding Protein-beta/metabolism , Interleukin-1beta/genetics , Protein Interaction Maps , Proto-Oncogene Proteins/metabolism , Trans-Activators/metabolism , Transcriptional Activation , Animals , Binding Sites , CCAAT-Enhancer-Binding Protein-beta/chemistry , Cell Line , Crystallography, X-Ray , Humans , Mice , Molecular Docking Simulation , Promoter Regions, Genetic , Protein Conformation , Proto-Oncogene Mas , Proto-Oncogene Proteins/chemistry , Trans-Activators/chemistry
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