Modulation of yeast Erg1 expression and terbinafine susceptibility by iron bioavailability.

Ergosterol is a specific sterol component of yeast and fungal membranes. Its biosynthesis is one of the most effective targets for antifungal treatments. However, the emergent resistance to multiple sterol-based antifungal drugs emphasizes the need for new therapeutic approaches. The allylamine terbinafine, which selectively inhibits squalene epoxidase Erg1 within the ergosterol biosynthetic pathway, is mainly used to treat dermatomycoses, whereas its effectiveness in other fungal infections is limited. Given that ergosterol biosynthesis depends on iron as an essential cofactor, in this report, we used the yeast Saccharomyces cerevisiae to investigate how iron bioavailability influences Erg1 expression and terbinafine susceptibility. We observed that both chemical and genetic depletion of iron decrease ERG1 expression, leading to an increase in terbinafine susceptibility. Deletion of either ROX1 transcriptional repressor or CTH1 and CTH2 post-transcriptional repressors of ERG1 expression led to an increase in Erg1 protein levels and terbinafine resistance. On the contrary, overexpression of CTH2 led to the opposite effect, lowering Erg1 levels and increasing terbinafine susceptibility. Although strain-specific particularities exist, opportunistic pathogenic strains of S. cerevisiae displayed a response similar to the laboratory strain. These data indicate that iron bioavailability and particular regulatory factors could be used to modulate susceptibility to terbinafine.

Workshop on Blood Loss Quantification in Obstetrics: Improving Medical Student Learning through Clinical Simulation.

PURPOSE: To assess whether a clinical simulation-based obstetric blood loss quantification workshop for medical undergraduate trainees improves theoretical-practical knowledge, along with self-assurance and self-confidence. METHODS: This was a quasi-experimental pre-post learning study conducted at the Gynaecology and Obstetrics Unit of the Hospital Gregorio Marañón, Madrid, Spain. Participants were volunteer students in their fourth year of a 6-year degree course in Medicine. The study period was divided into the stages: pre-workshop, intra-workshop, 2 weeks post-workshop and 6 months post-workshop. In the pre-workshop stage, students completed a brief online course in preparation for the workshop. The effectiveness of the workshop was assessed through multiple choice tests and self-administered questionnaires. Data were compared between time-points using statistical tests for paired samples. RESULTS: Of the 142 students invited (age 21.94 ± 3.12 years), 138 accepted the offer of the workshop (97.2%), and 85.4% had no experience in managing blood loss. Between the stages pre- and 2 weeks post-workshop, significant improvements were observed in theoretical-practical knowledge (µ = 1.109), self-assurance and self-confidence. At the 6 months post-workshop stage, theoretical-practical knowledge diminished compared with 2 weeks post-workshop, returning to pre-workshop levels, while self-assurance and confidence failed to vary significantly in the longer term. CONCLUSIONS: The obstetric workshop improved theoretical-practical knowledge and the self-assurance and confidence of the medical students. Results 2 weeks post-workshop were maintained up until 6 months after the training intervention. The clinical simulation-based workshop was perceived by the students as useful and necessary.