Evaluation problemorientierten Lernens im Münchner Modell der Medizinerausbildung - Bewertung durch die Studierenden (1997 bis 2001)

This research report is concerned with the evaluation of problem-oriented learning in medicine, i.e. the Munich Model of medicine education. First, key concepts of problem-oriented learning and their realisation in medical education are outlined. Then, the Munich Model of medicine education which has been established in cooperation with the Harvard Medical School, Boston, is described. Four problem-oriented courses are part of this model. Approximately 1.500 students participated in these courses. The aim of the evaluation is to provide a basis for improving the quality of the four problem-oriented courses. Evaluation dimensions are acceptance, subjective learning gains, group cooperation and tutor's support. The report shows the students' ratings of all courses conducted since 1997. The evaluation results are described for each course. Furthermore, between-course comparisons are reported. In general, students are very satisfied with the courses. Findings are discussed and future research is outlinedIn diesem Forschungsbericht wird die Evaluation des Münchner Modells problemorientierten Lernens in der Medizin beschrieben. Zunächst werden Schlüsselkonzepte problemorientierten Lernens und deren Umsetzung in der Medizinerausbildung dargestellt. Danach wird das Münchner Modell der Medizinerausbildung erläutert, in dem vier problemorientierte Kurse realisiert werden. Dieses wurde in Kooperation mit der Harvard Medical School, Boston, entwickelt. An den vier Kursen nahmen bisher insgesamt annähernd 1.500 Studierende teil. Ziel der Evaluation ist es, eine Grundlage zur weiteren Qualitätsverbesserung der vier problemorientierten Kurse bereitzustellen. Die Studierenden bewerten im Rahmen der Evaluation die Dimensionen Akzeptanz, subjektiver Lernerfolg, Gruppenkooperation und Betreuung durch den Tutor. In diesem Bericht werden die Teilnehmerbewertungen aller Kurse seit 1997 dargestellt. Die Evaluationsergebnisse werden für jeden Kurs erläutert. Darüber hinaus werden Vergleiche zwischen den Kursen berichtet. Insgesamt sind die Studierenden sehr zufrieden mit den Kursen. Die Befunde werden in Zusammenhang mit Fragestellungen zukünftiger Forschung diskutier

Cryo-Electron Microscopy to Investigate Molecular Dynamics and Conformational Changes in Protein Complexes

Stress can be considered as one of the most fundamental aspects in life, and all living organisms are constantly exposed to a variety of different stress situations. Thus, efficient stress sensing and reaction mechanisms are crucial for their survival. Stress response mechanisms are as diverse as the causative stimuli and oftentimes cross-linked forming a versatile reaction network, to ensure the cells’ survival under critical situations. Notably, stress response mechanisms play a major role in pathogenicity, virulence and disease. Pathogenic Bacteria are permanently facing environmental pressure originating from the host’s defense systems or drug treatments, while mutations in eukaryotic stress response systems have been shown to cause a large number of severe human diseases such as diabetes, cancer or Parkinson’s and Alzheimer’s disease. A profound molecular knowledge on the respective mechanisms is thus the inevitable prerequisite towards a global understanding of this fundamental aspect of life, paving the way for the development of new drugs or therapeutic approaches. Within this thesis, various aspects of stress response mechanisms in three different systems were investigated using state-of-the-art electron microscopy techniques. First, I set out to solve the structure of the Vibrio vulnificus stressosome complex, a key player in the bacterial environmental stress response. Currently, there is no structural data available for any gram-negative stressosome. A medium-resolution cryo-electron microscopy (cryo-EM) structure of the minimal complex could be obtained, which features an exceptional symmetry break originating from its unique, regulatory stoichiometry. Based on the structural data, it was possible to propose an activation mechanism and to pinpoint a number of significant differences in comparison to gram-positive stressosome complexes. Undoubtedly, the structure contributes a major piece of information necessary to understand stress sensing and signal transduction in this human pathogen. This study was complemented by a number of physiological and phylogenetic experiments contributed by our co-workers, and published recently (VIII. PUBLICATION 1). The second project focused on the gram-positive soil bacterium Corynebacterium glutamicum, a prime model organism for investigations of the bacterial osmostress response. Sensing of hyper-osmotic stress and regulation of the respective stress response in C. glutamicum are simultaneously performed by BetP, a conformationally asymmetric-trimeric secondary active transporter able to import the compatible solute betaine. Two stimuli are identified to initiate the full osmostress response in BetP, namely an elevated cytoplasmic K+ concentration and a loosely defined ‘membrane stimulus’. Despite the availability of functional data on BetP regulation, structural information especially of the down-regulated state and the subsequent transition events are absent. Using single particle cryo-EM analysis, I was able to provide high-resolution structures of the down-regulated and a transition state, which elucidated a number of important structural features not described so far. It could be shown that down-regulated BetP adopts a symmetric arrangement stabilized by antight cytoplasmic interaction network of the sensory domain, further strengthened by Cardiolipin molecules located at regulatory lipid binding sites. These constraints are released upon stress sensing, as demonstrated by fourier transform infrared (FTIR) spectroscopy and molecular dynamics simulation (MD) data contributed by our co-workers, resulting in the well-established, asymmetric-trimeric structures previously known. The wealth of new data on the down-regulated state allowed to propose a detailed regulation mechanism and to further sharpen the previously vague picture of the membrane stimulus. The data are summarized and presented in IX. PREPRINT 1. A third topic of this thesis was the three dimensional investigation via dual-axis scanning transmission electron microscopy (STEM) tomography of crystalloid-ER structures we identified before in human embryonic kidney (HEK) cells upon over-expression of polycystin-2 (PC-2). In this study presented in X. MANUSCRIPT 1, I was further able to proof the presence of ER whorls, and to obtain high-resolution three-dimensional (3D) reconstructions of the two different ER morphotypes. These data provided unmatched insights into the cellular ER interaction partners and clearly demonstrated the dynamic nature of the organelle even under stress situations. A detailed discussion of the identified morphological features in their respective cellular context finally allowed for the description of the organellar membrane architecture at a high level of detail. Lastly, the discussion addresses the electron microscopy techniques and instruments used and contains an outlook on further perspectives for the projects. Overall, this thesis yielded intriguing mechanistic insights into the versatile bacterial and eukaryotic stress response mechanisms, reflecting their manifold nature ultimately converging to a common outcome

Causes of Mortality and Diseases in Farmed Deer in Switzerland

To investigate diseases and causes of mortality in Swiss farmed deer, deer found dead or shot due to diseased condition between March 2003 and December 2004 were requested for a complete postmortem examination. One hundred and sixty-two animals were submitted. Perinatal mortality, necrobacillosis in 3 week to 6 month old deer, and endoparasitosis in 6 month to 2 year old deer were identified as the most important causes of loss, followed by ruminal acidosis, which was diagnosed in 22% of deer older than 1 year. Congenital malformations were observed in 15% of deer less than 6 months old. Reportable infectious diseases known as major problems in deer farming in other countries were rare (yersiniosis, malignant catarrhal fever) or not observed (tuberculosis, chronic wasting disease). Overall, the results indicate that the Swiss deer population does not present major health problems of concern for domestic animals

Gastric lactobezoar - a rare disorder?

Gastric lactobezoar, a pathological conglomeration of milk and mucus in the stomach of milk-fed infants often causing gastric outlet obstruction, is a rarely reported disorder (96 cases since its first description in 1959). While most patients were described 1975-1985 only 26 children have been published since 1986. Clinically, gastric lactobezoars frequently manifest as acute abdomen with abdominal distension (61.0% of 96 patients), vomiting (54.2%), diarrhea (21.9%), and/or a palpable abdominal mass (19.8%). Respiratory (23.0%) and cardiocirculatory (16.7%) symptoms are not uncommon. The pathogenesis of lactobezoar formation is multifactorial: exogenous influences such as high casein content (54.2%), medium chain triglycerides (54.2%) or enhanced caloric density (65.6%) of infant milk as well as endogenous factors including immature gastrointestinal functions (66.0%), dehydration (27.5%) and many other mechanisms have been suggested. Diagnosis is easy if the potential presence of a gastric lactobezoar is thought of, and is based on a history of inappropriate milk feeding, signs of acute abdomen and characteristic features of diagnostic imaging. Previously, plain and/or air-, clear fluid- or opaque contrast medium radiography techniques were used to demonstrate a mass free-floating in the lumen of the stomach. This feature differentiates a gastric lactobezoar from intussusception or an abdominal neoplasm. Currently, abdominal ultrasound, showing highly echogenic intrabezoaric air trapping, is the diagnostic method of choice. However, identifying a gastric lactobezoar requires an investigator experienced in gastrointestinal problems of infancy as can be appreciated from the results of our review which show that in not even a single patient gastric lactobezoar was initially considered as a possible differential diagnosis. Furthermore, in over 30% of plain radiographs reported, diagnosis was initially missed although a lactobezoar was clearly demonstrable on repeat evaluation of the same X-ray films. Enhanced diagnostic sensitivity would be most rewarding since management consisting of cessation of oral feedings combined with administration of intravenous fluids and gastric lavage is easy and resolves over 85% of gastric lactobezoars. In conclusion, gastric lactobezoar is a disorder of unknown prevalence and is nowadays very rarely published, possibly because of inadequate diagnostic sensitivity and/or not yet identified but beneficial modifications of patient management

How Religious Styles Develop: Longitudinal, Cross-cultural and Multi-method Research with Faith Development Interviews. Wave III Hypotheses for the JTF-funded Project ”Faith Development Revisited“

Streib H, Chen Z, Keller B, et al. How Religious Styles Develop: Longitudinal, Cross-cultural and Multi-method Research with Faith Development Interviews. Wave III Hypotheses for the JTF-funded Project ”Faith Development Revisited“. OSF . 2019

A thermoresponsive and magnetic colloid for 3D cell expansion and reconfiguration

A dual thermoresponsive and magnetic colloidal gel matrix is described for enhanced stem-cell culture. The combined properties of the material allow enzyme-free passaging and expansion of mesenchymal stem cells, as well as isolation of cells postculture by the simple process of lowering the temperature and applying an external magnetic field. The colloidal gel can be reconfigured with thermal and magnetic stimuli to allow patterning of cells in discrete zones and to control movement of cells within the porous matrix during culture

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were requested for a complete postmortem examination. One hundred and sixty-two animals were submitted. Perinatal mortality, necrobacillosis in 3 week to 6 month old deer, and endoparasitosis in 6 month to 2 year old deer were identified as the most important causes of loss, followed by ruminal acidosis, which was diagnosed in 22% of deer older than 1 year. Congenital malformations were observed in 15% of deer less than 6 months old. Reportable infectious diseases known as major problems in deer farming in other countries were rare (yersiniosis, malignant catarrhal fever) or not observed (tuberculosis, chronic wasting disease). Overall, the results indicate that the Swiss deer population does not present major health problems of concern for domestic animals

Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore

Arginine-rich cell-penetrating peptides do not enter cells by directly passing through a lipid membrane; they instead passively enter vesicles and live cells by inducing membrane multilamellarity and fusion. The molecular picture of this penetration mode, which differs qualitatively from the previously proposed direct mechanism, is provided by molecular dynamics simulations. The kinetics of vesicle agglomeration and fusion by an iconic cell-penetrating peptide-nonaarginine-are documented via real-time fluorescence techniques, while the induction of multilamellar phases in vesicles and live cells is demonstrated by a combination of electron and fluorescence microscopies. This concert of experiments and simulations reveals that the identified passive cell penetration mechanism bears analogy to vesicle fusion induced by calcium ions, indicating that the two processes may share a common mechanistic origin.Peer reviewe

Sarcopenia in Neurological Patients: Standard Values for Temporal Muscle Thickness and Muscle Strength Evaluation.

Temporal muscle thickness (TMT) was investigated as a novel surrogate marker on MRI examinations of the brain, to detect patients who may be at risk for sarcopenia. TMT was analyzed in a retrospective, normal collective cohort (n = 624), to establish standard reference values. These reference values were correlated with grip strength measurements and body mass index (BMI) in 422 healthy volunteers and validated in a prospective cohort (n = 130) of patients with various neurological disorders. Pearson correlation revealed a strong association between TMT and grip strength (retrospective cohort, ρ = 0.746; p < 0.001; prospective cohort, ρ = 0.649; p < 0.001). A low or no association was found between TMT and age (retrospective cohort, R2 correlation coefficient 0.20; p < 0.001; prospective cohort, ρ = -0.199; p = 0.023), or BMI (retrospective cohort, ρ = 0.116; p = 0.042; prospective cohort, ρ = 0.227; p = 0.009), respectively. Male patients with temporal wasting and unintended weight loss, respectively, showed significantly lower TMT values (p = 0.04 and p = 0.015, unpaired t-test). TMT showed a high correlation with muscle strength in healthy individuals and in patients with various neurological disorders. Therefore, TMT should be integrated into the diagnostic workup of neurological patients, to prevent, delay, or treat sarcopenia