Quantitative risk assessment: an emerging tool for emerging foodborne pathogens.

New challenges to the safety of the food supply require new strategies for evaluating and managing food safety risks. Changes in pathogens, food preparation, distribution, and consumption, and population immunity have the potential to adversely affect human health. Risk assessment offers a framework for predicting the impact of changes and trends on the provision of safe food. Risk assessment models facilitate the evaluation of active or passive changes in how foods are produced, processed, distributed, and consumed

Quantitative analysis of subcellular biomechanics and mechanotransduction

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004.Includes bibliographical references.Biological cells such as endothelial or muscle cells respond to mechanical stimulation with activation of specific intracellular and extracellular signaling pathways and cytoskeletal remodeling, a process termed mechanotransduction. Intracellular mechanosensors are thought to be activated by conformational changes induced by local cellular deformations. Since these mechanosensors have been speculated to be located in several cellular domains including the cell membrane, the cytoskeleton, and the nucleus, it is necessary to achieve a detailed understanding of subcellular mechanics. In this work, we present novel methods to independently quantify cytoskeletal displacements, mechanical coupling between the cytoskeleton and the extracellular matrix, and nuclear mechanics based on high resolution tracking of cellular structures and receptor bound magnetic beads in response to applied strain or microscopic forces. These methods were applied to study the effects of several human disease associated mutations on subcellular mechanics and to examine the interaction between known protein function and specific changes in cellular mechanical properties and mechanotransduction pathways. Initial experiments were targeted to the role of membrane adhesion receptors. Experiments with cells expressing a mutant form of the integrin-associated molecule tetraspanin CD151 revealed that CD151 plays a key role in selectively strengthening α6βl integrin-mediated adhesion to laminin-1. We then studied cytoplasmic behavior using cells from mice with an αB-Crystallin mutation (R120G) that causes desmin-related myopathy. These studies showed impaired passive cytoskeletal mechanics in adult mouse cardiac myocytes. Finally, we studied cells deficient in the nuclear envelope(cont.) protein lamin A/C and showed that lamin A/C deficient cells have increased nuclear deformation, defective mechanotransduction, and impaired viability under mechanical strain, suggesting that the tissue specific effects observed in laminopathies such as Emery-Dreifuss muscular dystrophy or Hutchinson-Gilford progeria may arise from varying degrees of impaired nuclear mechanics and transcriptional regulation. In conclusion, our methods provide new and valuable tools to examine the role of subcellular biomechanics on mechanotransduction in normal and mutant cells, leading to improved understanding of disease mechanisms associated with altered cell mechanics.by Jan Lammerding.Ph.D

Faculty Development Initiatives in Medical Education in German-Speaking Countries : I. State of affairs

Maßgeblich unter dem wachsenden externen Druck hat die didaktische Qualifizierung in den medizinischen Fakultäten an Bedeutung gewonnen. Im Rahmen der Professionalisierung der medizinischen Aus-, Fort- und Weiterbildung ist eine pädagogisch-didaktische Ausbildung der Lehrenden unumgänglich. Um Orientierung und Argumentationshilfe zu geben, werden in einer dreiteiligen Artikelfolge Stellenwert der Medizindidaktik, Anforderungsprofil der Angebote und Konzepte zur Implementierung und zur Erfolgsmessung für den deutschsprachigen Raum beleuchtet. In Teil I geben wir eine Bestandsaufnahme zur Medizindidaktik. Aktuell gibt es bundesweit ein breit gefächertes Qualifizierungsangebot. Es reicht von einfachen unstrukturierten Kurzfortbildungen wie zum Beispiel Vorträgen und Seminaren, die inhaltlich, formal und qualitativ eine große Beliebigkeit zeigen, bis hin zu umfassenden mehrjährigen (Aufbau-)Studiengängen mit "Master-Degree". Im internationalen Vergleich fehlt in Deutschland ein allgemein verbindliches "Basis-Programm", das die täglich Lehrenden systematisch auf ihre Ausbildungsaufgaben vorbereitet. Dies ist bisher nur lokal umgesetzt wie zum Beispiel in Baden-Württemberg mit dem ministeriell zertifizierten Programm der Medizindidaktischen Qualifikation I und II. Vergleichbares ist in Nordrhein-Westfalen und Bayern im Aufbau.In recent years, quality management of educational skills of medical teachers has gained increasing relevance, predominantly triggered by rising external pressure. Meanwhile, a consensus is reached that a professional training in pedagogical methods and didactic skills is essential for medical teachers in UGME and PGME. A series of three articles intends to provide not only a brief overview, but also detailed argumentative support concerning pedagogical aspects of medical education, the conceptual design and the implementation of faculty development programs in medical education. Additionally the important topic of how the effectiveness of staff development programs can be demonstrated will be addressed. The goal of the first article is to outline the present situation, conditions and recognition of teacher's training programs in German-speaking countries. At present, a variety of faculty development programs and activities have been designed and implemented. These activities include e.g. non-structured short courses and lectures, workshops and seminars of one to six days, as well as longitudinal programs up to national, two-year postgraduate programs to achieve the degree of a "Master of Medical Education" in Swiss and Germany. Compared to the international situation, in Germany is a lack of a mandatory basic program for all teaching staff members, which systematically provides a broad range of teaching and learning strategies for diverse settings. Only one regional faculty development program has been established so far in the federal state of Baden-Wurttemberg, which has been certified as "Medical Education Qualification, Step I and II" by the federal state ministry responsible for higher education. Two comparable programs are on the way in the federal states of Bavaria and North-Rhine-Westfalia

Faculty development initiatives in medical education in German-speaking countries : II. needs assessment and quality criteria

Maßgeblich unter dem wachsenden externen Druck hat die didaktische Qualifizierung in den medizinischen Fakultäten an Bedeutung gewonnen. Im Rahmen der Professionalisierung der medizinischen Aus-, Fort- und Weiterbildung ist eine pädagogisch-didaktische Ausbildung der Lehrenden unumgänglich. Um Orientierung und Argumentationshilfe zu geben, werden in einer dreiteiligen Artikelfolge Stellenwert der Medizindidaktik, Anforderungsprofil der Angebote und Konzepte zur Implementierung und zur Erfolgsmessung für den deutschsprachigen Raum beleuchtet. In Teil II beleuchten wir den Ausbildungsbedarf und erstellen ein Anforderungsprofil für ein strukturiertes systematisches Qualifizierungsangebot. Der Hauptbedarf besteht in der Qualifizierung der Lehrenden, die den täglichen Unterricht durchführen. Insbesondere sie brauchen das Handwerkszeug, das ihnen erlaubt, ihre verschiedenen Lehraufgaben effizienter zu bewältigen. Seitens der Fakultät und der Studierenden bestehen Ansprüche an qualifizierte Lehrende; ebenso bestehen Forderungen seitens der Lehrenden an adäquat qualifizierende Kurse. Zur Umsetzung dieser berechtigten Ansprüche sind modular aufgebaute Programme nötig, die eine zumindest national qualitativ und quantitativ vergleichbare Ausbildung gewährleisten. Anforderungen an derartige Kurse sind bereits definiert und lokal zum Beispiel in Baden-Württemberg und zum Teil auch in Nordrhein-Westfalen umgesetzt. Es gilt nun, diese auf breiter Basis in die Praxis umzusetzen.In recent years, quality management of didactic skills of medical teachers has gained increasing relevance, predominately triggered by rising external pressure. Meanwhile, a consensus is reached that a professional training in pedagogical methods and didactic skills is essential for medical teachers in UGME and PGME. A triple series of articles intends to provide not only a brief overview, but also detailed argumentative support concerning pedagogical aspects of medical education, the conceptual design and the implementation of faculty development programs in medical education. Additionally the important topic of how the effectiveness of staff development programs can be demonstrated will be addressed. The goal of the first article was to outline the actual situation, conditions and acknowledgment of teacher's training programs in German-speaking countries. The second article focuses on the needs assessment and on quality criteria of a systematic and comprehensive teachers' training. The most urgent necessity is the preparation of faculty members that cover the daily teaching routine. The teachers require a broad range of teaching and learning strategies that can be used in diverse settings and that enable them to fulfill their multiple roles more efficiently and effectively. Both medical school and students demand for qualified teachers; and faculty members call for professional opportunities to acquire the essential teaching skills and tools. Modular-designed training programs are necessary, which keep at least national minimal standards: A catalogue of quality criteria for such training programs has been defined and already implemented in Baden-Württemberg, and partly in North-Rhine-Westfalia. These criteria are described to make them adoptable for other places

Lamin A/C and emerin regulate MKL1/SRF activity by modulating actin dynamics

Laminopathies, caused by mutations in the LMNA gene encoding the nuclear envelope proteins lamins A and C, represent a diverse group of diseases that include Emery-Dreifuss Muscular Dystrophy (EDMD), dilated cardiomyopathy (DCM), limb-girdle muscular dystrophy, and Hutchison-Gilford progeria syndrome (HGPS).1 The majority of LMNA mutations affect skeletal and cardiac muscle by mechanisms that remain incompletely understood. Loss of structural function and disturbed interaction of mutant lamins with (tissue-specific) transcription factors have been proposed to explain the tissue-specific phenotypes.1 We report here that lamin A/C-deficient (Lmna−/−) and Lmna N195K mutant cells have impaired nuclear translocation and downstream signaling of the mechanosensitive transcription factor megakaryoblastic leukaemia 1 (MKL1), a myocardin family member that is pivotal in cardiac development and function.2 Disturbed nucleo-cytoplasmic shuttling of MKL1 was caused by altered actin dynamics in Lmna−/− and N195K mutant cells. Ectopic expression of the nuclear envelope protein emerin, which is mislocalized in Lmna mutant cells and also linked to EDMD and DCM, restored MKL1 nuclear translocation and rescued actin dynamics in mutant cells. These findings present a novel mechanism that could provide insight into the disease etiology for the cardiac phenotype in many laminopathies, whereby lamins A/C and emerin regulate gene expression through modulation of nuclear and cytoskeletal actin polymerization

Das „Sandwich-Prinzip“ – Einführung in Lerner zentrierte Lehr-Lernmethoden in der Medizin

Lernen ist ein hochindividueller Prozess, der von zahlreichen Faktoren, wie Vorwissen, Aufmerksamkeit, Lerninteresse und Motivation abhängt. Effizientes Lernen erscheint deshalb nur durch Ermöglichung individueller Lernphasen im Unterricht erreichbar. Die Sandwicharchitektur von Lehrveranstaltungen stellt ein übergeordnetes Prinzip dar, das durch Einsatz verschiedenster didaktischer Methoden kollektive und individuelle Lernphasen integriert und so effiziente Lernprozesse unterstützt

Alterations in peptide levels in Parkinson's disease and incidental Lewy body disease

The levels of the neuropeptides Met- and Leu-enkephalin (MET-ENK, LEU-ENK), substance P and neurotensin were measured by a combined high performance liquid chromatography/radioimmunoassay (HPLC/RIA) method in postmortem samples of basal ganglia from Parkinson's disease patients, incidental Lewy body disease patients (presymptomatic Parkinson's disease) and matched controls. Dopamine (DA) levels were reduced in the caudate nucleus and putamen in Parkinson's disease, but unaltered in incidental Lewy body disease. The levels of MET-ENK were reduced in the caudate nucleus, putamen and substantia nigra in Parkinson's disease. Met-enkephalin levels were reduced in the caudate nucleus and in the putamen in incidental Lewy body disease. Leu-enkephalin levels were decreased in the putamen and were undetectable in the substantia nigra in Parkinson's disease. Leu-enkephalin levels were unchanged in incidental Lewy body disease, although there was a tendency to a reduction in putamen. Substance P levels were reduced in the putamen in Parkinson's disease. No significant changes in substance P content were observed in incidental Lewy body disease. Neurotensin levels were increased in the substantia nigra in Parkinson's disease. Neurotensin levels in incidental Lewy body disease were not altered significantly, but tended to parallel the changes in Parkinson's disease. The changes in basal ganglia peptide levels in incidental Lewy body disease generally followed a trend similar to those seen in Parkinson's disease, but were less marked. This suggests that they are an integral part of the pathology of the illness and not secondary to DA neuronal loss or a consequence of prolonged drug therapy.Peer Reviewe

Faculty development initiatives in Medical Education in German-Speaking Countries : III. Aspects of successful implementation

Eine erfolgreiche Implementierung medizindidaktischer Qualifizierungsmaßnahmen setzt zwingend voraus, dass die Fakultäten nicht nur für entsprechende Angebote, sondern mittelfristig auch für lehrförderliche Rahmenbedingungen sorgen. Dabei müssen sowohl institutionelle Aspekte, die sich aus der Struktur und Funktion der Fakultät als Organisation ergeben als auch individuelle Aspekte der Zielgruppe der Lehrenden berücksichtigt werden. Von institutioneller Seitemuss vor allem Dermatologie und Deutschland die für alle sichtbare Unterstützung des Programms sichergestellt werden. Ebenfalls von zentraler Bedeutung ist die Bereitschaft, die medizindidaktische Qualifikation als einen wesentlichen Baustein der akademischen Laufbahn zu bewerten. Im Hinblick auf die Lehrenden geht es vor allem darum, das Angebot bekannt zu machen und seinen Nutzen herauszustellen, was mit Hilfe karrierebezogener Anreize naturgemäß leichter ist.To implement faculty development programs successfully it is absolutely essential that medical schools do not only provide adequate courses but do also offer surrounding conditions conducive to teaching. Institutional aspects that arise from structure and function of the medical school as an organisation as well as individual aspects that refer to the target group of medical teachers have to be taken into account. Looking at the institutional aspects it is especially important that official support of the program is assured and visible for everybody. Another institutional requirement is that expertise in teaching is regarded as an integral component of academic careers in medical education. Regarding medical teachers it is important to make faculty development programs known to them and to emphasise their benefit which is of course a lot easier by means of career incentives

Focused didactic training for skills lab student tutors – which techniques are considered helpful?

Objective: Peer-assisted learning is widely used in medical education. However, little is known about an appropriate didactic preparation for peer tutors. We herein describe the development of a focused didactic training for skills lab tutors in Internal Medicine and report on a retrospective survey about the student tutors’ acceptance and the perceived transferability of attended didactic training modules