Scientific publications of the Saarland University
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Nanofat promotes wound healing in skin following exposure to ionizing radiation
Get PDFRadiotherapy, while effective in cancer treatment, can lead to side effects, such as radiodermatitis with potential long-term consequences including telangiectasias, ulceration and fibrosis of the skin, eventually resulting in impaired wound healing. In this study, we analyzed whether the healing of such challenging wounds can be improved by nanofat (NF). NF is generated by mechanical emulsification and filtration of fat samples and, thus, is a random mixture of adipose-derived stem cells, microvascular fragments, extracellular matrix components and growth factors. Two months after localized ionizing radiation of the skin with a total dose of 20 Gy, full-thickness wounds were created in dorsal skinfold chambers of mice, which were filled with platelet-rich plasma (PRP; control, n = 8) or NF fixed in PRP (PRP + NF, n = 8). The healing process was assessed by means of stereomicroscopy, intravital fluorescence microscopy, histology and immunohistochemistry over 14 days. The closure of PRP + NF-treated wounds was accelerated, as indicated by significantly smaller wound areas on day 14 when compared to controls. This was associated with a higher density of blood-perfused microvessels inside the wounds. Moreover, PRP + NF-treated wounds showed a tendency towards an improved granulation tissue formation, lymphatic drainage and M2/M1 macrophage ratio. Taken together, these findings suggest that the application of NF represents a promising therapeutic strategy for the management of complex wounds in irradiated skin
Tidal volume and mortality during extracorporeal membrane oxygenation for acute respiratory distress syndrome: a multicenter observational cohort study
Get PDFBackground
Approximately half of the patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) remain ECMO-dependent beyond 14 days after ECMO initiation. The identification of factors associated with mortality during an ECMO run may update prognostic assessment and focus clinical interventions.
Methods
In this observational study, data from 1137 patients with COVID-19 ARDS receiving ECMO support in 29 German centers between January 1st 2020 and July 31st 2021 were analyzed. Multivariable stepwise logistic regression analyses were performed to build survival prediction models with day-by-day data during the first 14 days of an ECMO run. The primary endpoint was all-cause mortality in the intensive care unit.
Results
Mortality in this cohort was high (75%). Patients who remained ECMO-dependent on day 14 of their ECMO run showed comparable mortality to all patients receiving ECMO support on day 1. Yet, factors associated with mortality changed during the first 14 days of ECMO support. On day 1 of ECMO support, only patient age and lactate remained in the final mortality prediction model. On day 14 of an ECMO run, tidal volume was independently associated with mortality (adjusted Odds Ratio 0.693 (95%CI 0.564–0.851), p < 0.001 for 1 mL/kg increase in tidal volume per predicted body weight). The adjusted mortality for patients with a tidal volume below 2 mL/kg on day 14 of their ECMO run was above 80% (lower limit of the 95%CI interval). Higher tidal volume was mainly based on higher respiratory system compliance. Yet, the benefit of higher compliance was not observed in some patients who were still ventilated with very low driving pressures despite remaining ECMO-dependent on day 14 of ECMO support.
Conclusions
Mortality predictors change during the course of an ECMO run. In a cohort with high mortality, on day 14 of ECMO support for ARDS, tidal volume may be an independent predictor of mortality. Further analyses on ventilation strategies in patients who remain ECMO-dependent are needed.
Trial registration number
DRKS00022964, retrospectively registered
Structural DNMT-nucleosome contacts are related to DNA methylation patterns
Get PDFDNA-methylation is a key epigenetic mark in chromatin that attenuates chromatin accessibility during transcription,
implying a crucial role in gene regulation. Its symmetrical distribution and function is thought to be linked to
the periodicity of the DNA helix and the positioning of DNA wrapped around the nucleosome. Epigenomic data
suggest that DNA methyltransferases (DNMTs) can methylate DNA when wrapped around a histone octamer.
Yet, how this is precisely linked to positioning and periodicity is yet to be elucidated. It has been hypothesized
that the observed methylation patterns may be related to the changing accessibility of nucleosome-bound
DNA to DNMTs. Here, incorporating NOMe-Seq data, which simultaneously measures nucleosome positioning
and DNA methylation at CpG sites across the genome, the interaction of DNMT1 with nucleosomal DNA could
be mechanistically modeled and compared to hypothesized dependencies. Furthermore, X-ray structures of
DNMT1 were superimposed onto those of nucleosome core complexes at base resolution to determine which
histone-bound DNA positions would be sterically accessible or inaccessible to DNMTs. Statistical comparison with
experimental NOMe-Seq data revealed that structurally computed DNA accessibility scores can indeed explain DNA
methylation patterns in actively transcribed regions with positioned high nucleosome density
Empathie-Training für Lehramtsstudierende: Evaluierung verschiedener Trainingsformen und Persistenz der Effekte
Get PDFEmpathie ist nicht nur in alltäglichen zwischenmenschlichen Beziehungen unerlässlich, sondern auch in einer Arbeitswelt erforderlich, in der soziale Interaktionen im Vordergrund stehen. Besonders für Lehrkräfte ist Empathie eine notwendige Fähigkeit, um ihren Beruf effektiv ausüben zu können. Aus diesem Grund sollte die Empathie von Lehramtsstudierenden gefördert werden. Im Rahmen diesen Forschungsprojekts wurde ein achtwöchiges Empathie-Training für Lehramtsstudierende in Seminarform entwickelt und dessen Wirksamkeit bereits in einer Pilotstudie evaluiert. Diese Pilotstudie konnte bereits zeigen, dass durch das Training die Empathie der Teilnehmenden, insbesondere der Aspekt der Perspektivenübernahme, verbessert werden kann (Paulus & Meinken, 2022a). Aufbauend auf den ersten Ergebnissen wird in dieser Dissertation die Frage untersucht, ob ökonomischere Trainingsformen die Empathie, insbesondere die Perspektivenübernahme, ebenfalls anhaltend verbessert können. Zeit- und ressourcensparende Trainingsformen und die Persistenz der Trainingseffekte sind insbesondere im Hinblick auf ihren praktischen Nut-zen von großer Bedeutung. So wurde das Training sowohl in Seminarform modifiziert als auch hinsichtlich ökonomischer Aspekte weiterentwickelt. Demnach wurde das Training ne-ben der modifizierten Seminarform, auch in Blockform an jeweils 1,5 Tagen in Präsenz, in Online-Blockform an 1,5 Tage online und in Eintagesform an einem Tag in Präsenz durchgeführt. Die Stichprobe der Untersuchung besteht aus insgesamt 134 Lehramtsstudierenden, die an einem der Empathie-Trainings teilgenommen haben. 25 Personen nahmen an dem Training in Seminarform teil, insgesamt 61 Personen absolvierten das Training in Blockform, 26 Personen in Online-Blockform und 22 Personen in Eintagesform. Zur Überprüfung der Trainingseffekte wurden vor und nach dem Training jeweils zwei Fragebögen verwendet, die die Empathie der Teilnehmenden erfassen. Der merkmalsorientierte Saarbrücker Persönlichkeitsfragebogen (SPF) wurde hierfür mit der kontextspezifischen Jefferson Scale of Empathy for Teachers (JSE-T) ergänzt. Bei der Evaluierung wurden insbesondere die Items der Perspektivenübernahme berücksichtigt. Für die Evaluation der Persistenz wurden Messungen in verschiedenen Zeitabständen nach Trainingsende durchgeführt. Die Messung mit dem längsten zeitlichen Abstand, die für alle Trainingsformen durchgeführt wurde, war 4 Monate nach Trainingsende. Nach dem Training zeigten sich bei den Teilnehmenden in allen Trainingsformen deutliche Verbesserungen in der Perspektivenübernahme und in der generellen Einstellung zu empathischem Verhalten im schulischen Kontext. Zudem können in den ökonomischen Präsenz-Trainingsformen (Blockform & Eintagesform) deutliche Verbesserungen festgestellt werden, die vergleichbar mit dem Training in der zeitintensiveren Seminarform sind. In Seminar- und Blockform halten die Ergebnisse über 4 Monate nach Trainingsende mit großem Trainingserfolg in Seminar- (g = 1.35) und Blockform (g = .73) an. Sowohl in der Eintagesform als auch in der Online-Blockform weisen die Ergebnisse daraufhin, dass eine anhaltende Verbesserung der Perspektivenübernahme durch diese Trainingsformen möglich ist. Allerdings lassen sich auf Grundlage der vorliegenden Untersuchungen keine tragfähigen Schlussfolgerungen hinsichtlich der Persistenz des Trainings in diesen Formen ziehen. Insbesondere für das Training in Online-Blockform ist aus Sicht der Ökonomisierung weitere Forschung angebracht. Insgesamt zeigen die Ergebnisse, dass ein Empathie-Training in zeitintensiver, aber auch in ökonomischer Form die Empathie von Lehramtsstudierenden anhaltend verbessern kann. Diese Erkenntnis legt nahe, das Empathie-Training systematisch in die praktische Lehramtsausbildung zu implementieren. Darüber hinaus lässt sich ein Potenzial zur Übertragung des Trainings auf weitere Berufsgruppen ableiten, wodurch der gesellschaftliche Nutzen gezielt ausgeweitet werden kann
Stereoselective Syntheses of Cyclic Microsclerodermin Derivatives
Get PDFStarting from l-xylose and d-arabinose, six different cyclic microscleroderma derivatives were successfully obtained. Key steps of the syntheses are, on the one hand, Sakurai allylations, whose stereochemical course depends on the Lewis acid used, and on the other hand, photochemical Wolff rearrangements in the presence of complex aminofuranosides. Finally, aromatic side chains were introduced via cross metathesis
Promoting future teachers’ pedagogical knowledge: The role of self-generated vs. provided illustrative examples after instruction
Get PDFIllustrative examples demonstrate how abstract information can be applied in real-world. In the context of advancing evidence-informed teaching practice, the current intervention study investigated to what extent student teachers should be supported in learning educational theories and findings by different example-based approaches. Conducting a 1 × 3-factorial design, N = 105 student teachers were randomly assigned to three experimental groups: After a pre-test, all groups received the same learning instruction on the topic of cooperative learning. Then, (1) n = 35 students were prompted to generate own examples for the instructional text, (2) n = 35 students received examples along with the text, and (3) n = 35 students studied the text only, without any prompts or examples. In a post-questionnaire, it was retrospectively assessed how students perceived their learning control in engaging with the material; in a post-test, knowledge retention and knowledge transfer were measured. As assumed, findings revealed that generating examples enhanced perceived learning control and learning outcomes compared to studying provided examples. Students who learned with the instructional text only achieved lowest learning outcomes; but contrary to the expectations, these students perceived their learning control comparably high as those who generated examples. Mediation analyses indicated that for students who received illustrative examples or the instructional text only, a greater learning control perception was positively associated with knowledge retention, subsequently enhancing knowledge transfer. The study underscores the benefits of illustrative examples in teacher education, particularly when students engage in generating them. It suggests further examination of how and why example generation facilitates learning
Editorial: Introducing industry and practice notes - strengthening the bridge between research and practice in operations management
Get PDFDo Dogs Really Influence How People Evaluate Psychotherapists? A Conceptual Replication Attempt
Get PDFThe icebreaker effect – the idea that integrating animals into psychotherapy improves the therapeutic alliance – is believed to be one of the main mechanisms of action in animal-assisted psychotherapy. Support for this notion has come from preliminary evidence that the presence of a dog positively influences how people perceive psychotherapists. However, the robustness and generalizability of these findings have yet to be tested. Thus, in our study, we aimed to (1) conceptually replicate these results and (2) gain insight into what might drive them by employing a design with high experimental control. Four hundred and eighty-one participants took part in our experiment, in which they first watched a video of a psychotherapist introducing themself. In the video, we experimentally manipulated whether the psychotherapist had an additional qualification in animal-assisted therapy or in meditation techniques and mindfulness (as a control condition), whether the psychotherapist referred to this additional qualification in the video, whether this additional qualification was visible in the video (dog or meditation accessories visible), and the psychotherapist's gender. After watching the video, participants were asked to report on the anticipated therapeutic relationship, the perceived trustworthiness of the therapist, and their own willingness to self-disclose. None of our analyses yielded any evidence of positive effects from the presence of a dog in the video. Thus, we could not replicate the previous results. Given our design, we argue that our results suggest that it is neither the mere presence of the dog (i.e., the visibility of the dog in the video) nor the perception of the psychotherapist's ability to work with a dog as an additional qualification that drove the previously found positive effects. Instead, we discuss the idea that these positive effects might be due to (potentially unconscious) changes in psychotherapists’ behavior and performance when accompanied by a dog. We invite future research to investigate (1) the role that therapists’ behavioral changes due to the presence of a dog play and (2) under which circumstances these changes occur
A tailored approach towards the right dose of dasatinib, (E)-clomiphene, imatinib and infliximab leveraging physiologically based pharmacokinetic and population pharmacokinetic modeling
Get PDFThe overall aim of precision medicine is to provide the right treatment to the right patient at the right time and, consequently, improving clinical outcome and minimizing toxicities. However, substantial inter- and intra-individual variability in drug exposure and response often impedes successful treatment which calls for tailoring drug therapy to individual needs. Here, precision dosing represents an essential component of precision medicine to improve individual drug treatment. Despite the application of therapeutic drug monitoring or pharmacogenetic testing to optimize the dose for specific drugs, a significant need for advanced dosing strategies remains. Model-informed precision dosing, a crucial development in personalized medicine, uses pharmacometric models to guide clinicians in making dosing decisions by predicting tailored dosing regimens for individual patients or specific patient populations. This thesis aimed to develop and provide mechanistic pharmacometric models for the two tyrosine kinase inhibitors dasatinib and imatinib as well as for the selective estrogen receptor modulator (E)-clomiphene and an empirical pharmacometric model for the monoclonal antibody infliximab, helping to enhance treatment efficacy and reduce the risk of toxicities. These models and their presented applications may be leveraged to foster future precision dosing efforts in healthcare.Zu den Hauptzielen der Präzisionsmedizin gehört die Anwendung der richtigen Therapie für den richtigen Patienten zum richtigen Zeitpunkt, um die klinische Wirksamkeit zu verbessern und Toxizitäten zu minimieren. Einer erfolgreichen Arzneimitteltherapie steht häufig eine hohe inter- und intra-individuelle Variabilität im Ansprechen an die Therapie entgegen. Das Konzept der Präzisionsdosierung ist daher eine wichtige Komponente der Präzisionsmedizin. Doch trotz der Anwendung von Therapeutischem Drug-Monitoring oder pharmakogenetischer Tests für vereinzelte Arzneistoffe zur individuellen Dosisoptimierung besteht weiterhin ein großer Bedarf an fortschrittlicheren Dosierungsstrategien: Mit der Modell-informierten Präzisionsdosierung, die eine Weiterentwicklung in der Präzisionsmedizin darstellt, können basierend auf pharmakometrischen Modellen und Patienten-bezogenen Informationen individuelle Dosen für Patienten oder Patientengruppen vorhergesagt werden. Das Ziel dieser Thesis war es, mechanistische pharmakometrische Modelle für die beiden Tyrosin Kinase Inhibitoren Dasatinib und Imatinib und den selektiven Estrogen-Rezeptor Inhibitor (E)-Clomifen zu entwickeln sowie ein empirisches pharmakometrisches Modell für den monoklonalen Antikörper Infliximab bereitzustellen. Diese Modelle können zukünftig für individuelle Dosisanpassungen in der Klinik angewendet werden, um höhere Therapieansprechraten zu erzielen und das Risiko für Toxizitäten zu minimieren