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  • 1
    Abstract: OBJECTIVE: The initial steps of pancreatic regeneration versus carcinogenesis are insufficiently understood. Although a combination of oncogenic Kras and inflammation has been shown to induce malignancy, molecular networks of early carcinogenesis remain poorly defined. DESIGN: We compared early events during inflammation, regeneration and carcinogenesis on histological and transcriptional levels with a high temporal resolution using a well-established mouse model of pancreatitis and of inflammation-accelerated KrasG12D-driven pancreatic ductal adenocarcinoma. Quantitative expression data were analysed and extensively modelled in silico. RESULTS: We defined three distinctive phases-termed inflammation, regeneration and refinement-following induction of moderate acute pancreatitis in wild-type mice. These corresponded to different waves of proliferation of mesenchymal, progenitor-like and acinar cells. Pancreas regeneration required a coordinated transition of proliferation between progenitor-like and acinar cells. In mice harbouring an oncogenic Kras mutation and challenged with pancreatitis, there was an extended inflammatory phase and a parallel, continuous proliferation of mesenchymal, progenitor-like and acinar cells. Analysis of high-resolution transcriptional data from wild-type animals revealed that organ regeneration relied on a complex interaction of a gene network that normally governs acinar cell homeostasis, exocrine specification and intercellular signalling. In mice with oncogenic Kras, a specific carcinogenic signature was found, which was preserved in full-blown mouse pancreas cancer. CONCLUSIONS: These data define a transcriptional signature of early pancreatic carcinogenesis and a molecular network driving formation of preneoplastic lesions, which allows for more targeted biomarker development in order to detect cancer earlier in patients with pancreatitis.
    Type of Publication: Journal article epub ahead of print
    PubMed ID: 27646934
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Zeitschrift für Medizinische Ausbildung; VOL: 26; DOC22 /20090515/
    Publication Date: 2009-05-16
    Description: Aims: An interactive surgical logbook was introduced in 2004 as part of a reform of the 16-week surgical training period of the final medical year at Heidelberg University. The present work describes its aims and development and examines its utilization by students and supervising doctors over a period of four years. Methods: The surgical training period of the final medical year was evaluated in 2003 by means of questionnaires and interviews with doctors, nurses, orderlies, and final-year medical students. Subsequently, a catalog of training objectives was compiled, which formed the basis for a logbook that states the training objectives, outlines the curriculum of the surgical training period, and includes separate pages for documenting 31 different medical procedures including the treatment of three patients under one's care. It further includes tables for recording one's attendance at training activities and detachable forms for self-assessment, evaluation of the surgical training period, and assessment of the student by the training doctors. The logbook was given to all students in their final-year surgical training period, but its use was optional. The entries in all returned logbooks were retrieved, recorded, and analyzed. Results: The return rate of the logbooks was initially low but rose within two years to 80%-100%. The extent of the entries was, however, continuously poor. Nineteen percent of the logbooks were devoid of entries, approximately 40% had no entries of clinical procedures, and the majority of the rest contained very incomplete records. The extent of feedback and comments by the supervising doctors was very limited, and their assessment forms often were filled in by the students themselves. By contrast, students returned numerous self-assessment and evaluation questionnaires that were complete and contained differentiated entries. Informal interviews with students revealed that cooperation was lacking on the part of the training doctors, and the long hours spent in the operating room placed considerable restrictions on the regular use of the logbook. However, low motivation of students who are not interested in surgery must also be considered. Conclusion: The interactive surgical logbook developed in cooperation with final-year medical students is potentially an effective measure for promoting the acquisition of a targeted learning strategy and individually designing one's own training program. Its efficiency, however, depends on active support by the training doctors and motivation on the part of the students. To overcome these limitations, we intend to modify the logbook and integrate it into a mandatory competence-based tutoring program in the future.
    Description: Zielsetzung: Im Rahmen einer Reform des chirurgischen Tertials des Praktischen Jahres (PJ) an der Chirurgischen Universitätsklinik Heidelberg wurde 2004 ein interaktives chirurgisches Logbuch eingeführt. Die Arbeit beschreibt seine Entwicklung und untersucht seine Anwendung durch die Studierenden und das Lehrpersonal in einem Zeitraum von vier Jahren. Methode: 2003 wurde das chirurgische Tertial durch schriftliche Fragebögen und Interviews mit Ärzten, Pflegepersonal und PJ-Studierenden evaluiert. Die Ziele des Tertials wurden neu konkretisiert und ein Lernzielkatalog konzipiert. Auf dessen Basis wurde ein Logbuch entwickelt, in dem die Studierenden ihre klinischen Tätigkeiten während des Tertials fortlaufend dokumentieren und analysieren sollen. Das Logbuch definiert die Lernziele des Tertials, umfasst 31 zu dokumentierende Verfahren einschließlich der Behandlung eigener Patienten sowie Formulare zur Selbsteinschätzung, Beurteilung durch Dozenten, Evaluation des Tertials und Teilnahme an Lehrveranstaltungen. Das Logbuch wird an alle PJ-Studierenden ausgeteilt, seine Anwendung und Rückgabe sind jedoch freiwillig. Die Einträge aller zurückgegebenen Logbücher wurden tabellarisch erfasst und analysiert. Ergebnisse: Die anfänglich niedrige Rücklaufquote stieg innerhalb von zwei Jahren auf 80-100%. Die Eintragungen waren jedoch fortwährend dürftig: 19% der abgegebenen Logbücher enthielten gar keine Einträge, ca. 40% keine Einträge zu den aufgeführten klinischen Fertigkeiten. Die Mehrheit der restlichen Logbücher enthielt Einträge nur für einen kleinen Teil der zu erlernenden Prozeduren, die überdies vorwiegend sehr unvollständig waren. Kontrolle und Rückmeldung durch die Dozenten waren sehr begrenzt. Im Gegensatz dazu wurden von den Studierenden zahlreiche Selbsteinschätzungs- und Evaluationsbögen vollständig und differenziert ausgefüllt zurückgegeben. Informelle Gespräche mit Studierenden ergaben, dass mangelnde Kooperation seitens der begleitenden Ärzte und lange Aufenthalte im OP wesentliche Hindernisse für die regelmäßige Anwendung des Logbuches darstellen. Mangelnde Motivation der Studierenden muss ebenfalls bedacht werden. Schlussfolgerung: Das durch Mitwirkung der Studierenden entwickelte interaktive Logbuch ist eine potentiell höchst wirksame Maßnahme, die den Ausbau einer gezielten Lernstrategie und Selbstgestaltung eines vollständigen Trainingsprogramms fördern kann. Sein effektiver Gebrauch ist jedoch von einer aktiven Unterstützung der begleitenden Ärzte und der Motivation der Studierenden abhängig. Um diese Hindernisse zu umgehen, beabsichtigen wir in Zukunft, das Logbuch als Grundlage für ein verpflichtendes kompetenzbasiertes Tutorensystem zu modifizieren.
    Keywords: Medical education ; final-year undergraduate training ; surgery ; logbook ; interactive logbook ; portfolio ; compliance ; evaluation ; self-assessment ; competence ; Medizinische Ausbildung ; Praktisches Jahr ; Chirurgie ; Logbuch ; interaktives Logbuch ; Portfolio ; Compliance ; Evaluation ; Selbsteinschätzung ; Kompetenz ; ddc: 610
    Language: German
    Type: article
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  62. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie; 20160414-20160415; Münster; DOCP1.3 /20160225/
    Publication Date: 2016-02-26
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  128. Kongress der Deutschen Gesellschaft für Chirurgie; 20110503-20110506; München; DOC11dgch055 /20110520/
    Publication Date: 2011-05-20
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 5
  • 6
    Abstract: Fungal infections are major causes of morbidity and mortality, especially in immunocompromised individuals. The innate immune system senses fungal pathogens through Syk-coupled C-type lectin receptors (CLRs), which signal through the conserved immune adaptor Card9. Although Card9 is essential for antifungal defense, the mechanisms that couple CLR-proximal events to Card9 control are not well defined. Here, we identify Vav proteins as key activators of the Card9 pathway. Vav1, Vav2, and Vav3 cooperate downstream of Dectin-1, Dectin-2, and Mincle to engage Card9 for NF-kappaB control and proinflammatory gene transcription. Although Vav family members show functional redundancy, Vav1/2/3-/- mice phenocopy Card9-/- animals with extreme susceptibility to fungi. In this context, Vav3 is the single most important Vav in mice, and a polymorphism in human VAV3 is associated with susceptibility to candidemia in patients. Our results reveal a molecular mechanism for CLR-mediated Card9 regulation that controls innate immunity to fungal infections.
    Type of Publication: Journal article published
    PubMed ID: 27926862
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  • 7
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Zeitschrift für Medizinische Ausbildung; VOL: 25; DOC89 /20080815/
    Publication Date: 2008-08-15
    Description: Background: The final clinical year of undergraduate medical training in Germany aims at providing more practical experience. However, most hospitals lack a structured curriculum. The Department of General Surgery at Heidelberg University, therefore, developed a systematic curriculum for this training period. Methods: In designing the new curriculum, we followed Kern's six-step approach to curriculum development . To assess needs, students, physicians, and nurses were asked in semi-structured interviews to give their views on existing as well as desirable educational contents. Results: The interview data showed that most tasks of final-year students were fulfilled without supervision. Even skills considered very important by professionals were not audited. The accomplishment of core competencies was thus accidental. On the basis of the interview data, learning objectives were formulated and translated into adequate teaching strategies. Conclusion: The present work shows the results of our needs assessment and may serve as a model for surgery departments of any teaching hospital in Germany.
    Description: Hintergrund: Das Praktische Jahr (PJ) soll die Umsetzung theoretischer Kenntnisse in die Praxis ermöglichen. Den meisten Ausbildungskliniken fehlt ein strukturiertes PJ-Curriculum. An der Chirurgischen Universitätsklinik Heidelberg wurde deshalb ein systematisches Curriculum für diesen Studienabschnitt entwickelt. Methoden: Die Curriculumsentwicklung folgte dem sechsstufigen Modell nach Kern . Grundlage war eine Bedarfsanalyse anhand halbstrukturierter Interviews mit Pflegepersonal, Ärzten und Studierenden, in denen deren Meinung zum existierenden Ausbildungsprogramm und zu wünschenswerten Verbesserungen abgefragt wurde. Ergebnisse: Die Analyse der Ergebnisse ergab, dass die Ausbildung nicht ausreichend auf den Arztberuf vorbereitet. Die meisten Fertigkeiten wurden durch Studierende ohne jegliche Supervision durchgeführt, der Erwerb von Kernkompetenzen blieb dem Zufall überlassen. Auf der Basis der Interviewdaten wurden Lernziele formuliert und in adäquate Lehrstrategien übersetzt. Schlussfolgerung: Die vorliegende Arbeit zeigt die Ergebnisse der Bedarfsanalyse und kann auf jede chirurgische Abteilung deutscher Ausbildungskliniken übertragen werden.
    Keywords: medical education ; needs assessment ; final-year undergraduate curriculum ; surgery ; Medizinische Ausbildung ; Strukturiertes Curriculum für das Praktische Jahr ; Chirurgie ; Bedarfsanalyse ; ddc: 610
    Language: German
    Type: article
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  • 8
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  45. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung; 20190509-20190511; Wien; DOC19oegu025 /20190408/
    Publication Date: 2019-04-09
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 9
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  62. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie; 20160414-20160415; Münster; DOCV2.10 /20160225/
    Publication Date: 2016-02-26
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 10
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  62. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie; 20160414-20160415; Münster; DOCV2.1 /20160225/
    Publication Date: 2016-02-26
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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