Enantioselektive Totalsynthese, biologische Aktivität und Strukturvariation des antitumoralen Alkaloids (-)-Dibromphakellstatin aus dem Meeresschwamm Phakellia mauritiana

Pyrrole-imidazole alkaloids represent a unique family of natural products which are exclusively found in marine sponges, mainly the Agelasidae, Axinellidae, and Halichondridae families. The pyrrole-imidazole alkaloids are fascinating due to thier biogenetic relationship leading to a large, strucurally diverse family based on a common key metabolite, oroidin. Some of the pyrrole-imidazole alkaloids have interesting biological activities, e. g., potent antitumor or antibacterial activities. One of these chellenging alkaloids is dibromophakellstatin which was first isolated from Phakellia mauritiana. In this work an efficient five step synthesis of dibromophakellstatin is described providing the natural product in an overall yield of 10%. Based on a broad investigation of the reactivity of dipyrrolopyrazinone-type enamides, a novel three component imidazolidinone anellation was exploited as the key step of the total synthesis. With this findings the overall yield of the synthesis could increased up to 18%. Based on these results it was possible to develope the first enantioselective total synthesis of (-)-dibromophakellstatin in a chiral pool approach (10 steps, 3.5% overall yield). In a collaboration effort the antitumor activity of dibromophakellstatin was confirmed. It was found that only the natural enantiomer shows biological activity by an unknown mechanism. Encouraged by the biological activity of (-)-dibromophakellstatin, different cyclopropane variations of the tetracyclic phakellin- and isophakellin scaffolds were obtained by reaction of dichlorocarbene with tri- and bicyclic precursors. Some of these compounds werde found to have interesting new anti proliferative activities

Адаптация опыта использования компьютерных программ-симуляторов для оценки компетенций студентов в процессе обучения

В рамках магистерской диссертации проведено исследование возможности адаптации компьютерных программ-симуляторов для оценки компетенций студентов в процессе обучения посредством изучения существующего международного и отечественного опыта использования программ-симуляторов в образовательной сфере, анализа нормативно-правовой базы, интервьюирования экспертов и проведения экспертного семинара.Within the framework of the master's thesis, the possibility of adapting computer simulators for assessing the competencies of students in the learning process was studied by studying the existing international and domestic experience in the use of simulator programs in the educational sphere, analyzing the regulatory framework, interviewing experts and holding an expert seminar

Detecting medication risks among people in need of care: performance of six instruments

Introduction: Numerous tools exist to detect potentially inappropriate medication (PIM) and potential prescribing omissions (PPO) in older people, but it remains unclear which tools may be most relevant in which setting. Objectives: This cross sectional study compares six validated tools in terms of PIM and PPO detection. Methods: We examined the PIM/PPO prevalence for all tools combined and the sensitivity of each tool. The pairwise agreement between tools was determined using Cohen’s Kappa. Results: We included 226 patients in need of care (median (IQR age 84 (80–89)). The overall PIM prevalence was 91.6 (95% CI, 87.2–94.9)% and the overall PPO prevalence was 63.7 (57.1–69.9%)%. The detected PIM prevalence ranged from 76.5%, for FORTA-C/D, to 6.6% for anticholinergic drugs (German-ACB). The PPO prevalences for START (63.7%) and FORTA-A (62.8%) were similar. The pairwise agreement between tools was poor to moderate. The sensitivity of PIM detection was highest for FORTA-C/D (55.1%), and increased to 79.2% when distinct items from STOPP were added. Conclusion: Using a single screening tool may not have sufficient sensitivity to detect PIMs and PPOs. Further research is required to optimize the composition of PIM and PPO tools in different settings

Detecting Medication Risks among People in Need of Care: Performance of Six Instruments

Introduction: Numerous tools exist to detect potentially inappropriate medication (PIM) and potential prescribing omissions (PPO) in older people, but it remains unclear which tools may be most relevant in which setting. Objectives: This cross sectional study compares six validated tools in terms of PIM and PPO detection. Methods: We examined the PIM/PPO prevalence for all tools combined and the sensitivity of each tool. The pairwise agreement between tools was determined using Cohen’s Kappa. Results: We included 226 patients in need of care (median (IQR age 84 (80–89)). The overall PIM prevalence was 91.6 (95% CI, 87.2–94.9)% and the overall PPO prevalence was 63.7 (57.1–69.9%)%. The detected PIM prevalence ranged from 76.5%, for FORTA-C/D, to 6.6% for anticholinergic drugs (German-ACB). The PPO prevalences for START (63.7%) and FORTA-A (62.8%) were similar. The pairwise agreement between tools was poor to moderate. The sensitivity of PIM detection was highest for FORTA-C/D (55.1%), and increased to 79.2% when distinct items from STOPP were added. Conclusion: Using a single screening tool may not have sufficient sensitivity to detect PIMs and PPOs. Further research is required to optimize the composition of PIM and PPO tools in different settings