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Item type: Item , Genome-Wide Association Study Reveals Single Nucleotide Polymorphisms Associated with Tail Length and Tail Kinks in Piglets(2025) Gerhards, Katharina; Egerer, Christiane; Becker, Sabrina; Willems, Hermann; Engel, Petra; Koenig, Sven; Reiner, GeraldTail docking is still used in pigs to reduce the prevalence of tail biting, although it is purely symptomatic and contrary to animal welfare. Genetic selection for shorter tails might, however, help to avoid tail docking and has therefore been proposed. A genetic basis for tail length is known for many species. Variability in tail length, including moderate heritability, has also been demonstrated in pigs. The aim of the present study was to identify genetic markers for tail length and to define candidate genes. To this end, 140 piglets were phenotyped and genotyped at 3 days of age and a genome-wide association study was performed. Seven SNPs were mapped on chromosomes 1, 2, 6, 11, and 15. Two linked SNPs on chromosome 2 resulted in a functional amino acid exchange. The genotypes at the SNPs were only associated with small differences in relative tail length of up to 16.5% (short genotype versus long genotype at SSC15), but at the same time with the occurrence of malformations in the form of tail kinks. The small effect size and the association between tail length and tail kinks, together with the generally pure symptomatic effect on tail biting, argue against the applicability of selection for shorter tails in pigs.Item type: Item , Isoflurane vs. Propofol Sedation in Patients with Severe Stroke : A Clinical Proof-of-Concept-Study(2025) Worm, André; Claudi, Christian; Braun, Svea R.; Schenker, Marisa; Meyer, Anneke; Moeller, Leona; Simon, Ole J.; Timmermann, Lars; Mrochen, Anne; Diel, Norma J.; Juenemann, Martin; Huttner, Hagen B.; Schramm, PatrickBackground: Severe strokes often require deep sedation, yet the optimal sedation regimen remains unclear. This comparative study compared the efficacy of achieving target sedation depth using inhaled (isoflurane) versus intravenous (propofol) sedation. Methods: This prospective, observational, proof-of-concept study was conducted between July 2022 and June 2023 at two University Hospitals with dedicated neurological intensive care units. We included conservatively treated patients with severe space-occupying strokes (ischemic or haemorrhagic) requiring deep sedation. Patients received either inhaled or intravenous sedation. Sedation targets were defined in the morning rounds using the Richmond-Agitation-Sedation-Scale and were assessed at two subsequent time points (7 p.m. and 7 a.m.) during hospital stay. The primary outcome was the number of days where the predefined sedation target was achieved at both time points, comparing between the two sedation regimens. Secondary and safety outcomes included the incidence of delirium, pneumonia, functional outcomes, mortality, and vasopressor doses. Results: Seventy-nine patients (age 71 [63–81] years, 31 female) were included. Patients sedated with isoflurane achieved the sedation target significantly more often, with 182/444 (41%) compared to 80/497 (16%) assessments in patients sedated with propofol (RR 1.4; 95%-CI: 1.3–1.6). This effect was consistent across all sedation stages, specifically in the deep sedation targets (RR 1.5; 95%-CI: 1.2–1.9) and no-sedation target (RR 5.1; 95%-CI: 2.8–9.4). Secondary and safety outcomes revealed no significant differences. Conclusions: Isoflurane sedation offers a benefit for invasively ventilated stroke patients with respect to sedation targets. Specifically, isoflurane facilitates faster awakening when transitioning from deep sedation to awakening. These data encourage further confirmatory studies for specific stroke-patient groups.Item type: Item , Dobutamine, epinephrine, and milrinone accelerate particle transport velocity in murine tracheal epithelium via Ca2+ release from caffeine-sensitive internal stores(2025) Schmidt, Götz; Borchers, Frederic; Müller, Sabrina; Ali Akbari, Amir; Edinger, Fabian; Sander, Michael; Koch, Christian; Henrich, MichaelMucociliary clearance, the ability of the respiratory tract to protect the integrity of the airways through the mechanical removal of potentially harmful substances, is of enormous importance during intensive care treatment. The present study aimed to evaluate the influence of clinically relevant inotropic agents on mucociliary clearance. The particle transport velocity (PTV) of isolated murine tracheae was measured as a surrogate for mucociliary clearance in the presence of dobutamine, epinephrine, and milrinone. Inhibitory substances were applied to elucidate the signal transduction cascades and the value and origin of calcium ions which provoke alterations in mucociliary clearance function. Dobutamine, epinephrine, and milrinone increased the PTV in a dose-dependent manner with half maximal effective concentrations of 75.7 nM, 87.0 nM, and 13.7 µM, respectively. After the depletion of intracellular calcium stores, no increase in PTV was observed after administering any of the three inotropic agents. While dobutamine and epinephrine activated β-adrenergic receptors, epinephrine used both the phospholipase C (PLC) and protein kinase A (PKA) pathway to promote the release of intracellular Ca2+. However, dobutamine primarily acted on the PKA pathway, having only a minor influence on the PLC pathway. The induced changes in PTV following milrinone administration required both the PKA and PLC pathway, although the PKA pathway was responsible for most of the induced changes. In conclusion, the common inotropic agents dobutamine, epinephrine, and milrinone increase murine PTV in a concentration-dependent manner and ultimately release Ca2+ from intracellular calcium stores, suggesting the function of changes in mucociliary clearance in the respiratory tract.Item type: Item , Genetic and epigenetic intersections in COVID-19-associated cardiovascular disease: emerging insights and future directions(2025) Sabit, Hussein; Arneth, Borros; Altrawy, Afaf; Ghazy, Aysha; Abdelazeem, Rawan M.; Adel, Amro; Abdel-Ghany, Shaimaa; Alqosaibi, Amany I.; Deloukas, Panos; Taghiyev, Zulfugar T.The intersection of COVID-19 and cardiovascular disease (CVD) has emerged as a significant area of research, particularly in understanding the impact of antiplatelet therapies like ticagrelor and clopidogrel. COVID-19 has been associated with acute cardiovascular complications, including myocardial infarction, thrombosis, and heart failure, exacerbated by the virus’s ability to trigger widespread inflammation and endothelial dysfunction. MicroRNAs (miRNAs) play a critical role in regulating these processes by modulating the gene expressions involved in platelet function, inflammation, and vascular homeostasis. This study explores the potential of miRNAs such as miR-223 and miR-126 as biomarkers for predicting resistance or responsiveness to antiplatelet therapies in COVID-19 patients with cardiovascular disease. Identifying miRNA signatures linked to drug efficacy could optimize treatment strategies for patients at high risk of thrombotic events during COVID-19 infection. Moreover, understanding miRNA-mediated pathways offers new insights into how SARS-CoV-2 exacerbates CVD, particularly through mechanisms like cytokine storms and endothelial damage. The findings of this research could lead to personalized therapeutic approaches, improving patient outcomes and reducing mortality in COVID-19-associated cardiovascular events. With global implications, this study addresses the urgent need for effective management of CVD in the context of COVID-19, focusing on the integration of molecular biomarkers to enhance the precision of antiplatelet therapy.Item type: Item , Einfluss von 17-β-Estradiol und Dienogest auf humane primäre endometriale Epithelzellen im Kontext der Endometriose(2025) Kary, Franziska LouisaEndometriose ist eine Erkrankung, die mit der Disseminierung von Endometriumgewebe in extrauterine Körperbereiche einhergeht und dort zu einer Etablierung von ektopen Endometriose-Herden führt. Die Krankheit ist östrogenabhängig und meist assoziiert mit einer Progesteron-Resistenz. Ein medikamentöser Therapieansatz, der in der Behandlung der Endometriose und assoziierter Symptome Anwendung findet, ist die Therapie mit synthetischem Progesteron wie Dienogest. Ziel dieser Arbeit war es herauszufinden, welche Effekte E2 und Dienogest auf humane endometriale Epithelzellen haben und inwieweit diese den Progress oder die Entstehung der Endometriose beeinflussen könnten. Es konnte gezeigt werden, dass E2 generell einen verstärkenden Einfluss auf Parameter hat, die dazu beitragen könnten, Endometriose-Herde zu etablieren. E2 führte in den vorgestellten Experimenten zu einer Verringerung des TEERs, einer geringeren Expression des Zell-Kontakt-Proteins ZO1 und zu einer vermehrten Migration und Invasivität der Zelllinie eCRC560. Dienogest hingegen reduzierte die genannten Parameter sowohl bei alleiniger Gabe als auch in Kombination mit E2. Des Weiteren wurde die Sekretion von MMP7 untersucht, einer Matrix-Metalloproteinase, bei welcher bereits eine verstärkte Expression in Endometriose-Herden und auch in eutopem Gewebe von an Endometriose erkrankten Frauen, beobachtet werden konnte. In dieser Arbeit konnte unter Behandlung mit Dienogest eine signifikante Reduktion der MMP7-Sekretion von eCRC560 gezeigt werden. Bei zusätzlicher Stimulation mit E2 kam es zu einer weiteren Reduktion, was auf einen synergistischen Effekt der beiden Hormone hinweist. E2 allein führte ebenfalls zu einer geringen Reduktion. Der zweite Teil dieser Arbeit bezog sich auf die Wundheilung im Uterus. Die Fibroblasten des Endometriums exprimieren physiologischerweise kein CD26/DPP4, eine Protease, die mit Narbenbildung assoziiert ist. Entsprechend kommt es auch im Endometrium nur in Ausnahmefällen zur Narbenbildung. Es konnte gezeigt werden, dass das Zytokin IL1α, CD26 in der humanen endometrialen Stromazelllinie HPESC560 induziert. Diese Erkenntnis könnte zum besseren Verständnis der Pathogenese der Narbenbildung im Uterus beitragen.