Opportunity recognition in entrepreneurship education, design principles on fostering competent entrepreneurs in the science domain

This paper is part of a research project focusing on educational design principles that should help students with a background in Science to become competent with respect to opportunity recognition in business. The recognition of business opportunities is one of the basic competencies of entrepreneurs, and therefore needs attention in entrepreneurship education. Based on existing models, theories and prior experiences we developed and implemented several design principles in a course for students in a Master of Science and Business at Utrecht University. The evaluation and analysis of the learning process and the learning outcomes showed the merits of the principles on intrinsic motivation, avoiding environmental constraints, using prior knowledge and stimulating idea generation in the teaching of opportunity recognition

Living on Site While Renovating; Flexible Instructional Design of Post-Graduate Medical Training

BACKGROUND: Developing theoretical courses for post-graduate medical training that are aligned to current workplace-based learning practices and adaptive to change in the field is challenging, especially in (sub) specialties where time for re-design is limited and needs to be performed while education continues. APPROACH: An instructional design method was applied based on flexible co-design to improve post-graduate theoretical courses in child and adolescent psychiatry (CAP) in the Netherlands. In four phases over a period of three years, courses were re-designed at a national level. EVALUATION: Once common vision and learning goals were agreed upon and the prototype was developed (phases 1 and 2), the first courses could be tested in daily practice (phase 3). Phase 4 refined these courses in brief iterative cycles and allowed for designing additional courses building on and adding to previous experiences in brief iterative cycles. The resulting national theoretical courses re-allocated resources previously spent on a local level using easily accessible online tools. This allowed trainees to align content with their clinical rotations, personal preferences and training schedules. REFLECTION: The development of theoretical courses for post-graduate medical training in smaller medical (sub-)specialties with limited resources may profit from a flexible instructional design method. We consider the potential merit of such a method to other medical specialties and other (inter-)national efforts to develop theoretical teaching courses. A longer-term implementation evaluation is needed to show to what extent the investment made in the re-design proves to be future-proof and enables rapid adaptation to changes in the field

Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics

Aldosterone is synthesised by aldosterone synthase (CYP11B2). CYP11B2 has a highly homologous isoform, steroid 11β-hydroxylase (CYP11B1), which is responsible for the biosynthesis of aldosterone precursors and glucocorticoids. To investigate aldosterone biosynthesis and facilitate the search for selective CYP11B2 inhibitors, we constructed three-dimensional models for CYP11B1 and CYP11B2 for both human and rat. The models were constructed based on the crystal structure of Pseudomonas Putida CYP101 and Oryctolagus Cuniculus CYP2C5. Small steric active site differences between the isoforms were found to be the most important determinants for the regioselective steroid synthesis. A possible explanation for these steric differences for the selective synthesis of aldosterone by CYP11B2 is presented. The activities of the known CYP11B inhibitors metyrapone, R-etomidate, R-fadrazole and S-fadrazole were determined using assays of V79MZ cells that express human CYP11B1 and CYP11B2, respectively. By investigating the inhibitors in the human CYP11B models using molecular docking and molecular dynamics simulations we were able to predict a similar trend in potency for the inhibitors as found in the in vitro assays. Importantly, based on the docking and dynamics simulations it is possible to understand the enantioselectivity of the human enzymes for the inhibitor fadrazole, the R-enantiomer being selective for CYP11B2 and the S-enantiomer being selective for CYP11B1

Plant sterol or stanol esters retard lesion formation in LDL receptor-deficient mice independent of changes in serum plant sterols

Statins do not always decrease coronary heart disease mortality, which was speculated based on increased serum plant sterols observed during statin treatment. To evaluate plant sterol atherogenicity, we fed low density lipoprotein-receptor deficient (LDLr(+/-)) mice for 35 weeks with Western diets (control) alone or enriched with atorvastatin or atorvastatin plus plant sterols or stanols. Atorvastatin decreased serum cholesterol by 22% and lesion area by 57%. Adding plant sterols or stanols to atorvastatin decreased serum cholesterol by 39% and 41%. Cholesterol-standardized serum plant sterol concentrations increased by 4- to 11-fold during sterol plus atorvastatin treatment versus stanol plus atorvastatin treatment. However, lesion size decreased similarly in the sterol plus atorvastatin (-99% vs. control) and the stanol plus atorvastatin (-98%) groups, with comparable serum cholesterol levels, suggesting that increased plant sterol concentrations are not atherogenic. Our second study confirms this conclusion. Compared with lesions after a 33 week atherogenic period, lesion size further increased in controls (+97%) during 12 more weeks on the diet, whereas 12 weeks with the addition of plant sterols or stanols decreased lesion size (66% and 64%). These findings indicate that in LDLr(+/-) mice 1) increased cholesterol-standardized serum plant sterol concentrations are not atherogenic, 2) adding plant sterols/stanols to atorvastatin further inhibits lesion formation, and 3) plant sterols/stanols inhibit the progression or even induce the regression of existing lesions

Plant sterol or stanol esters retard lesion formation in LDL receptor-deficient mice independent of changes in serum plant sterols

Statins do not always decrease coronary heart disease mortality, which was speculated based on increased serum plant sterols observed during statin treatment. To evaluate plant sterol atherogenicity, we fed low density lipoprotein-receptor deficient (LDLr(+/-)) mice for 35 weeks with Western diets (control) alone or enriched with atorvastatin or atorvastatin plus plant sterols or stanols. Atorvastatin decreased serum cholesterol by 22% and lesion area by 57%. Adding plant sterols or stanols to atorvastatin decreased serum cholesterol by 39% and 41%. Cholesterol-standardized serum plant sterol concentrations increased by 4- to 11-fold during sterol plus atorvastatin treatment versus stanol plus atorvastatin treatment. However, lesion size decreased similarly in the sterol plus atorvastatin (-99% vs. control) and the stanol plus atorvastatin (-98%) groups, with comparable serum cholesterol levels, suggesting that increased plant sterol concentrations are not atherogenic. Our second study confirms this conclusion. Compared with lesions after a 33 week atherogenic period, lesion size further increased in controls (+97%) during 12 more weeks on the diet, whereas 12 weeks with the addition of plant sterols or stanols decreased lesion size (66% and 64%). These findings indicate that in LDLr(+/-) mice 1) increased cholesterol-standardized serum plant sterol concentrations are not atherogenic, 2) adding plant sterols/stanols to atorvastatin further inhibits lesion formation, and 3) plant sterols/stanols inhibit the progression or even induce the regression of existing lesion

Nerve Coaptation Improves the Sensory Recovery of the Breast in DIEP Flap Breast Reconstruction

Background: Restoring the sensation of the reconstructed breast has increasingly become a goal of autologous breast reconstruction. The aim of this study was to analyze the sensory recovery of the breast and donor site of innervated compared to noninnervated deep inferior epigastric perforator (DIEP) flap breast reconstructions, to assess associated factors, and to compare the differences between preoperative and postoperative sensation.Methods: A prospective cohort study was conducted, including patients who underwent innervated or noninnervated DIEP flap breast reconstruction between August of 2016 and August of 2018. Nerve coaptation was performed to the anterior cutaneous branch of the third intercostal nerve. Preoperative and postoperative sensory testing of the breast and donor site was performed with Semmes-Weinstein monofilaments.Results: A total of 67 patients with 94 innervated DIEP flaps and 58 patients with 80 noninnervated DIEP flaps were included. Nerve coaptation was significantly associated with lower mean monofilament values for the breast (-0.48; p &lt; 0.001), whereas no significant differences were found for the donor site (-0.16; p = 0.161) of innervated compared to noninnervated DIEP flaps. Factors positively or negatively associated with sensory recovery of the breast and donor site were identified. Preoperative versus postoperative comparison demonstrated significantly superior sensory recovery of the breast in innervated flaps (adjusted difference, -0.48; p = 0.017).Conclusions: This study demonstrated that nerve coaptation in DIEP flap breast reconstruction significantly improved the sensory recovery of the breast compared to noninnervated flaps. The sensory recovery of the donor site was not compromised in innervated reconstructions. The results support the role of nerve coaptation in autologous breast reconstruction.</p