Ethik First - extracurriculäre Unterstützung für Studierende und junge Ärzt*innen bei moralischen Dilemmata im Klinikalltag

Introduction: Moral value conflicts play an increasingly central role in everyday hospital life. Clinical ethics, however, is only marginally represented in the compulsory curriculum for human medicine and the additional education regulations. The aim of the Ethik First project at the University Medical Center Schleswig-Holstein, Campus Kiel is to close this gap with an extracurricular offer and to support medical students from the fifth clinical semester onward and during their practical year as well as assistant doctors in dealing with moral dilemmas in everyday hospital life. The project has taken the concomitant learning objectives from the national competency-based learning objective catalog for medicine. According to the target group, the address in particular, showed higher taxonomy levels. Project description: The multimodal concept is based on three pillars: In monthly principle-based case conferences, participants practice ethical reflection and moral judgment primarily on the basis of concrete cases introduced by them using the methods of problem-based learning and consideration-based deliberation. If participants do not bring forth a case, they discuss ethical aspects of current political relevance. Moreover, there is an annual public speaker event.Results: Since the project began in 2017, ~20 students and interns have taken part in Ethik First one or more times. In a web-based interim evaluation (N=13), all respondents fully agreed that they considered the format helpful for dealing with ethical questions at the clinic. They rated the relevance for their later profession as high. There is evidence for support in moral dilemma situations.Discussion: The first evaluation results of the voluntary extracurricular offer show the acceptance of the selected format, which goes beyond pure teaching in its conception in that it addresses moral stress as well and strengthens the participants' individual resilience.Conclusion: Ethik First reinforces the role of ethical aspects in the training of (prospective) doctors and focuses on reflecting on cases they have experienced firsthand. We formulate a desideratum for appropriate advanced training concepts both in medical studies and in advanced medical training such that the training and development of comparable projects at medical faculties and at medical associations with student participation can be discussed.Einleitung: Moralische Wertekonflikte spielen im Klinikalltag immer wieder und zunehmend eine zentrale Rolle. Klinische Ethik ist jedoch nur marginal im Pflichtcurriculum für Humanmedizin und den Weiterbildungsordnungen vertreten. Ziel des Projektes Ethik First am Universitätsklinikum Schleswig-Holstein, Campus Kiel ist es daher, diese Lücke mit einem extracurricularen Angebot zu schließen und Medizinstudierende ab dem 5. klinischen Semester sowie im Praktischen Jahr und Assistenzärzt*innen im Umgang mit moralischen Dilemmata im Klinikalltag zu unterstützen. Die damit einhergehenden Lernziele sind dem Nationalen Kompetenzbasierten Lernzielkatalog Medizin entnommen und adressieren der Zielgruppe entsprechend insbesondere höhere Taxonomiestufen. Projektbeschreibung: Das multimodale Konzept beruht auf drei Säulen: Vorrangig werden in monatlich stattfindenden prinzipienorientierten Fallkonferenzen ethische Reflexion und moralisches Urteilen anhand konkreter von den Teilnehmer*innen eingebrachter Fälle nach den Methoden des problembasierten Lernens und der erwägungsorientierten Deliberation eingeübt. Wird durch die Teilnehmer*innen kein Fall eingebracht, werden alternativ ethische Aspekte von aktueller tagespolitischer Relevanz gemeinsam diskutiert. Ergänzend findet jährlich eine öffentliche Veranstaltung eines*einer Referenten*in statt.Ergebnisse: Seit Beginn des Angebots im Jahr 2017 nahmen circa 20 Studierende und Assistenzärzt*innen ein- oder mehrmals an Ethik First teil. In einer webbasierten Zwischenevaluation (N=13) stimmten alle Befragten voll zu, dass sie das Format für hilfreich halten, um ethische Fragestellungen aus der Klinik zu bearbeiten. Die Relevanz für den späteren Beruf wurde hoch eingeschätzt. Es ergeben sich Anhalte für eine Unterstützung bei moralischen Dilemmasituationen.Diskussion: Erste Evaluationsergebnisse des freiwilligen extracurricularen Angebotes zeigen die Akzeptanz des gewählten Formates, das in seiner Konzeption über reine Lehre hinaus geht, indem auch moralischer Stress adressiert wird und die individuelle Resilienz der Teilnehmer*innen gestärkt werden soll.Schlussfolgerung: Ethik First stärkt die Rolle ethischer Aspekte in der Ausbildung von (angehenden) Ärzt*innen und stellt die Reflexion selbst erlebter Fälle in den Mittelpunkt. Wir formulieren ein Desiderat an entsprechenden Fort- und Weiterbildungskonzepten sowohl im Medizinstudium als auch in der ärztlichen Weiterbildung, sodass Aus- und Aufbau vergleichbarer Angebote an medizinischen Fakultäten und auch an den Ärztekammern mit studentischer Beteiligung diskutiert werden sollten

Solid-State Stability Issues of Drugs in Transdermal Patch Formulations

The transdermal patch formulation has many advantages, including noninvasiveness, an ability to bypass the first-pass metabolism, low dosage requirements, and prolonged drug delivery. However, the instability of solid-state drugs is one of the most critical problems observed in transdermal patch products. Therefore, a well-characterized approach for counteracting stability problems in solid-state drugs is crucial for improving the performance of transdermal patch products. This review provides insight into the solid-state stability of drugs associated with transdermal patch products and offers a comprehensive update on the various approaches being used for improving the stability of the active pharmaceutical ingredients currently being used

Palmitoylation is required for TNF-R1 signaling

Background Binding of tumor necrosis factor (TNF) to TNF-receptor 1 (TNF-R1) can induce either cell survival or cell death. The selection between these diametrically opposed effects depends on the subcellular location of TNF-R1: plasma membrane retention leads to survival, while endocytosis leads to cell death. How the respective TNF-R1 associated signaling complexes are recruited to the distinct subcellular location is not known. Here, we identify palmitoylation of TNF-R1 as a molecular mechanism to achieve signal diversification. Methods Human monocytic U937 cells were analyzed. Palmitoylated proteins were enriched by acyl resin assisted capture (AcylRAC) and analyzed by western blot and mass spectrometry. Palmitoylation of TNF-R1 was validated by metabolic labeling. TNF induced depalmitoylation and involvement of APT2 was analyzed by enzyme activity assays, pharmacological inhibition and shRNA mediated knock-down. TNF-R1 palmitoylation site analysis was done by mutated TNF-R1 expression in TNF-R1 knock-out cells. Apoptosis (nuclear DNA fragmentation, caspase 3 assays), NF-kappa B activation and TNF-R1 internalization were used as biological readouts. Results We identify dynamic S-palmitoylation as a new mechanism that controls selective TNF signaling. TNF-R1 itself is constitutively palmitoylated and depalmitoylated upon ligand binding. We identified the palmitoyl thioesterase APT2 to be involved in TNF-R1 depalmitoylation and TNF induced NF-kappa B activation. Mutation of the putative palmitoylation site C248 interferes with TNF-R1 localization to the plasma membrane and thus, proper signal transduction. Conclusions Our results introduce palmitoylation as a new layer of dynamic regulation of TNF-R1 induced signal transduction at a very early step of the TNF induced signaling cascade. Understanding the underlying mechanism may allow novel therapeutic options for disease treatment in future