@article{FreyGassenmaierHofmannetal.2020, author = {Frey, Anna and Gassenmaier, Tobias and Hofmann, Ulrich and Schmitt, Dominik and Fette, Georg and Marx, Almuth and Heterich, Sabine and Boivin-Jahns, Val{\´e}rie and Ertl, Georg and Bley, Thorsten and Frantz, Stefan and Jahns, Roland and St{\"o}rk, Stefan}, title = {Coagulation factor XIII activity predicts left ventricular remodelling after acute myocardial infarction}, series = {ESC Heart Failure}, volume = {7}, journal = {ESC Heart Failure}, number = {5}, doi = {10.1002/ehf2.12774}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236013}, pages = {2354-2364}, year = {2020}, abstract = {Aims Acute myocardial infarction (MI) is the major cause of chronic heart failure. The activity of blood coagulation factor XIII (FXIIIa) plays an important role in rodents as a healing factor after MI, whereas its role in healing and remodelling processes in humans remains unclear. We prospectively evaluated the relevance of FXIIIa after acute MI as a potential early prognostic marker for adequate healing. Methods and results This monocentric prospective cohort study investigated cardiac remodelling in patients with ST-elevation MI and followed them up for 1 year. Serum FXIIIa was serially assessed during the first 9 days after MI and after 2, 6, and 12 months. Cardiac magnetic resonance imaging was performed within 4 days after MI (Scan 1), after 7 to 9 days (Scan 2), and after 12 months (Scan 3). The FXIII valine-to-leucine (V34L) single-nucleotide polymorphism rs5985 was genotyped. One hundred forty-six patients were investigated (mean age 58 ± 11 years, 13\% women). Median FXIIIa was 118 \% (quartiles, 102-132\%) and dropped to a trough on the second day after MI: 109\%(98-109\%; P < 0.001). FXIIIa recovered slowly over time, reaching the baseline level after 2 to 6 months and surpassed baseline levels only after 12 months: 124 \% (110-142\%). The development of FXIIIa after MI was independent of the genotype. FXIIIa on Day 2 was strongly and inversely associated with the relative size of MI in Scan 1 (Spearman's ρ = -0.31; P = 0.01) and Scan 3 (ρ = -0.39; P < 0.01) and positively associated with left ventricular ejection fraction: ρ = 0.32 (P < 0.01) and ρ = 0.24 (P = 0.04), respectively. Conclusions FXIII activity after MI is highly dynamic, exhibiting a significant decline in the early healing period, with reconstitution 6 months later. Depressed FXIIIa early after MI predicted a greater size of MI and lower left ventricular ejection fraction after 1 year. The clinical relevance of these findings awaits to be tested in a randomized trial.}, language = {en} } @article{TraubGrondeyGassenmaieretal.2022, author = {Traub, Jan and Grondey, Katja and Gassenmaier, Tobias and Schmitt, Dominik and Fette, Georg and Frantz, Stefan and Boivin-Jahns, Val{\´e}rie and Jahns, Roland and St{\"o}rk, Stefan and Stoll, Guido and Reiter, Theresa and Hofmann, Ulrich and Weber, Martin S. and Frey, Anna}, title = {Sustained increase in serum glial fibrillary acidic protein after first ST-elevation myocardial infarction}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {18}, issn = {1422-0067}, doi = {10.3390/ijms231810304}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288261}, year = {2022}, abstract = {Acute ischemic cardiac injury predisposes one to cognitive impairment, dementia, and depression. Pathophysiologically, recent positron emission tomography data suggest astroglial activation after experimental myocardial infarction (MI). We analyzed peripheral surrogate markers of glial (and neuronal) damage serially within 12 months after the first ST-elevation MI (STEMI). Serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were quantified using ultra-sensitive molecular immunoassays. Sufficient biomaterial was available from 45 STEMI patients (aged 28 to 78 years, median 56 years, 11\% female). The median (quartiles) of GFAP was 63.8 (47.0, 89.9) pg/mL and of NfL 10.6 (7.2, 14.8) pg/mL at study entry 0-4 days after STEMI. GFAP after STEMI increased in the first 3 months, with a median change of +7.8 (0.4, 19.4) pg/mL (p = 0.007). It remained elevated without further relevant increases after 6 months (+11.7 (0.6, 23.5) pg/mL; p = 0.015), and 12 months (+10.3 (1.5, 22.7) pg/mL; p = 0.010) compared to the baseline. Larger relative infarction size was associated with a higher increase in GFAP (ρ = 0.41; p = 0.009). In contrast, NfL remained unaltered in the course of one year. Our findings support the idea of central nervous system involvement after MI, with GFAP as a potential peripheral biomarker of chronic glial damage as one pathophysiologic pathway.}, language = {en} } @article{GuederReinFlohretal.2023, author = {G{\"u}der, G{\"u}lmisal and Rein, Eva von and Flohr, Thomas and Weismann, Dirk and Schmitt, Dominik and St{\"o}rk, Stefan and Frantz, Stefan and Kratzer, Vincent and Kendi, Christian}, title = {Motion detectors as additional monitoring devices in the intensive care unit — a proof-of-concept study}, series = {Applied Sciences}, volume = {13}, journal = {Applied Sciences}, number = {16}, issn = {2076-3417}, doi = {10.3390/app13169319}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362404}, year = {2023}, abstract = {Background: Monitoring the vital signs of delirious patients in an intensive care unit (ICU) is challenging, as they might (un-)intentionally remove devices attached to their bodies. In mock-up scenarios, we systematically assessed whether a motion detector (MD) attached to the bed may help in identifying emergencies. Methods: We recruited 15 employees of the ICU and equipped an ICU bed with an MD (IRON Software GmbH, Gr{\"u}nwald, Germany). Participants were asked to replay 22 mock-up scenes of one-minute duration each: 12 scenes with movements and 10 without movements, of which 5 were emergency scenes ("lying dead-still, with no or very shallow breathing"). Blinded recordings were presented to an evaluation panel consisting of an experienced ICU nurse and a physician, who was asked to assess and rate the presence of motions. Results: Fifteen participants (nine women; 173 ± 7.0 cm; 78 ± 19 kg) joined the study. In total, 286 out of 330 scenes (86.7\%) were rated correctly. Ratings were false negative (FN: "no movements detected, but recorded") in 7 out of 180 motion scenes (3.9\%). Ratings were false positive (FP: "movements detected, but not recorded") in 37 out of 150 scenes (24.7\%), more often in men than women (26 out of 60 vs. 11 out of 90, respectively; p \< 0.001). Of note, in 16 of these 37 FP-rated scenes, a vibrating mobile phone was identified as a potential confounder. The emergency scenes were correctly rated in 64 of the 75 runs (85.3\%); 10 of the 11 FP-rated scenes occurred in male subjects. Conclusions: The MD allowed for identifying motions of test subjects with high sensitivity (96\%) and acceptable specificity (75\%). Accuracy might increase further if activities are recorded continuously under real-world conditions.}, language = {en} } @article{PollingerSchmittSanderetal.2017, author = {Pollinger, Florian and Schmitt, Stefan and Sander, Dirk and Tian, Zhen and Kirschner, J{\"u}rgen and Vrdoljak, Pavo and Stadler, Christoph and Maier, Florian and Marchetto, Helder and Schmidt, Thomas and Sch{\"o}ll, Achim and Umbach, Eberhard}, title = {Nanoscale patterning, macroscopic reconstruction, and enhanced surface stress by organic adsorption on vicinal surfaces}, series = {New Journal of Physics}, volume = {19}, journal = {New Journal of Physics}, doi = {10.1088/1367-2630/aa55b8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171947}, year = {2017}, abstract = {Self-organization is a promising method within the framework of bottom-up architectures to generate nanostructures in an efficient way. The present work demonstrates that self- organization on the length scale of a few to several tens of nanometers can be achieved by a proper combination of a large (organic) molecule and a vicinal metal surface if the local bonding of the molecule on steps is significantly stronger than that on low-index surfaces. In this case thermal annealing may lead to large mass transport of the subjacent substrate atoms such that nanometer-wide and micrometer-long molecular stripes or other patterns are being formed on high-index planes. The formation of these patterns can be controlled by the initial surface orientation and adsorbate coverage. The patterns arrange self-organized in regular arrays by repulsive mechanical interactions over long distances accompanied by a significant enhancement of surface stress. We demonstrate this effect using the planar organic molecule PTCDA as adsorbate and Ag(10 8 7) and Ag(775)surfaces as substrate. The patterns are directly observed by STM, the formation of vicinal surfaces is monitored by highresolution electron diffraction, the microscopic surface morphology changes are followed by spectromicroscopy, and the macroscopic changes of surface stress are measured by a cantilever bending method. The in situ combination of these complementary techniques provides compelling evidence for elastic interaction and a significant stress contribution to long-range order and nanopattern formation.}, language = {en} } @article{FreyPoppPostetal.2014, author = {Frey, Anna and Popp, Sandy and Post, Antonia and Langer, Simon and Lehmann, Marc and Hofmann, Ulrich and Siren, Anna-Leena and Hommers, Leif and Schmitt, Angelika and Strekalova, Tatyana and Ertl, Georg and Lesch, Klaus-Peter and Frantz, Stefan}, title = {Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain}, series = {Frontiers in Behavioral Neuroscience}, volume = {8}, journal = {Frontiers in Behavioral Neuroscience}, issn = {1662-5153}, doi = {10.3389/fnbeh.2014.00376}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118234}, pages = {376}, year = {2014}, abstract = {Background: Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF). However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI). Methods and Results: In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation. Mice with large MI and increased left ventricular dimensions on echocardiography (termed CHF mice) showed reduced preference for sucrose, indicating depression-like behavior. 6 weeks after MI, mice were tested for exploratory activity, anxiety-like behavior and cognitive function using the elevated plus maze (EPM), light-dark box (LDB), open field (OF), and object recognition (OR) tests. In the EPM and OF, CHF mice exhibited diminished exploratory behavior and motivation despite similar movement capability. In the OR, CHF mice had reduced preference for novelty and impaired short-term memory. On histology, CHF mice had unaltered overall cerebral morphology. However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI. Conclusions: After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment. Thus, ischemic CHF leads to distinct behavioral changes in mice analogous to symptoms observed in humans with CHF and comorbid depression.}, language = {en} } @phdthesis{Schmitt2007, author = {Schmitt, Stefan}, title = {Adsorbatinduzierte richtungsabh{\"a}ngige Facettierung und selbstorganisierte Dom{\"a}nen-Musterbildung auf vizinalen Ag(111)-Oberfl{\"a}chen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-25088}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {Die vorliegende Arbeit besch{\"a}ftigt sich mit den strukturellen Aspekten einer adsorbat-induzierten Facettierung von vizinalen Ag(111)-Oberfl{\"a}chen. Bei dem Adsorbat handelte es sich um das organische Molek{\"u}l Perylen-3,4,9,10-Tetracarbons{\"a}ure-Dianhydrid (PTCDA). Die Experimente wurden unter Ultrahochvakuum-Bedingungen durchgef{\"u}hrt, die Charakterisierung erfolgte haupts{\"a}chlich mit den Messmethoden Rastertunnelmikroskopie (STM) und niederenergetische Elektronenbeugung (LEED). Das planare Farbstoffmolek{\"u}l PTCDA adsorbiert pr{\"a}ferentiell an den Stufenkanten der verwendeten 8.5° Ag(111)-Vizinaloberfl{\"a}chen und induziert bei geeigneten Pr{\"a}parationsbedingungen eine Rekonstruktion in stark gestufte Facettenfl{\"a}chen und in stufenfreie (111)-Terrassen. Die beobachteten Facetten sind f{\"u}r das System PTCDA/Ag charakteristisch und stellen durch eine molekulare {\"U}berstruktur richtungsselektiv stabilisierte Ag-Kristallebenen dar. Durch die Variation der Stufenrichtung der Startoberfl{\"a}che wurde eine Vielzahl von Facettentypen erhalten und nach Miller indiziert. In ihrer Gesamtheit erlauben sie einen R{\"u}ckschluss auf das Aussehen der Gleichgewichtskristallform eines mit PTCDA bedeckten Ag-Kristalles und damit auf das richtungsabh{\"a}ngige Benetzungsverhalten von Ag. Aus der Sicht des Substrates bewirkt das Adsorbat eine massive Erh{\"o}hung der Steifheit der Stufen. Die durch eine molekulare {\"U}berstruktur stabilisierten Facettenfl{\"a}chen {\"u}bernehmen die in der Kristallstruktur des Substrates angelegten Stufenrichtungen. Die gefundene Ausbildung von zwei typischen Facettensteigungen ist jedoch nicht durch die Ag-Kristallstruktur motivierbar. Die Facettierung wurde im Rahmen einer speziellen Adaption des Konzepts der Thermodynamik auf ebene gestufte Oberfl{\"a}chen als Orientierungsphasenseparation beschrieben. Dieses Konzept erlaubt eine korrekte Beschreibung der beobachteten lokalen Ph{\"a}nomene und zeigt zudem auf, dass das molekulare Gas, welches in den Messungen nicht erfasst wurde, eine wichtige Rolle bei der Rekonstruktion spielt. Es ergaben sich wichtige Indizien f{\"u}r die Existenz einer kritischen Inselgr{\"o}ße f{\"u}r PTCDA auf Ag(111). Es wurde eine vollst{\"a}ndige strukturelle Analyse aller stabilen molekularen {\"U}berstrukturen auf vizinalen Ag(111)-Oberfl{\"a}chen durchgef{\"u}hrt. Es wurden insgesamt 16 solcher {\"U}berstrukturen gefunden, von denen bisher nur 3 Strukturen bekannt und ver{\"o}ffentlicht waren. Dichte und Kommensurabilit{\"a}t der Facetten{\"u}berstrukturen sind systematisch vom Stufentyp der Oberfl{\"a}che abh{\"a}ngig. Die Frage nach dem Ursprung der beiden charakteristischen Facettensteigungen ist mit der Existenz von zwei Typen von {\"U}berstrukturgrenzen verkn{\"u}pft. Die Grenze bestimmt die Lage der fischgr{\"a}tartigen {\"U}berstruktur zu den Stufenkanten und die L{\"a}nge und die Breite des Molek{\"u}ls die beiden charakteristischen Stufenabst{\"a}nde. Letzteres geschieht verm{\"o}ge einer lokalen Wechselwirkung der PTCDA-Molek{\"u}le mit den Stufen. Die {\"U}berstrukturgrenzen erweisen sich als wichtiges Element der Rekonstruktion. Es wurden außerdem die Abh{\"a}ngigkeiten der verschiedenen, aneinander angrenzenden {\"U}berstrukturen aufgezeigt. Auf den (111)-Terrassen fanden sich 3 metastabile Ausnahme-Strukturen, welche einen vertieften Einblick in die komplexe Bildungskinetik der bisher bekannten stabilen (111)-Struktur erlauben. Die Facetten bilden zusammen mit den benachbarten (111)-Terrassen regelm{\"a}ßige, einem Reflexionsgitter {\"a}hnliche Muster mit einer Strukturweite von 5 bis 75nm. Die beobachteten Strukturweiten erreichen bei ausgedehntem Tempern typische Maximalwerte. STM-Messungen zeigen den Einfluss einer langreichweitigen Wechselwirkung zwischen den Facetten, vermittelt {\"u}ber elastische Eigenschaften des Substrates. Die Muster k{\"o}nnen als selbstorganisierte Zweiphasensysteme im thermodynamischen Gleichgewicht erkl{\"a}rt werden. Die Facetten wirken wie repulsiv wechselwirkende Defekte in einem elastischen Medium. Die Eignung dieser Muster als Templat wurde in Kooperation mit einer anderen Arbeitsgruppe am Beispiel der selektiven Deposition von Eisen belegt.}, subject = {Adsorbat}, language = {de} } @article{UllmannSchmittRothetal.2014, author = {Ullmann, Tobias and Schmitt, Andreas and Roth, Achim and Duffe, Jason and Dech, Stefan and Hubberten, Hans-Wolfgang and Baumhauer, Roland}, title = {Land Cover Characterization and Classification of Arctic Tundra Environments by Means of Polarized Synthetic Aperture X- and C-Band Radar (PolSAR) and Landsat 8 Multispectral Imagery — Richards Island, Canada}, doi = {10.3390/rs6098565}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113303}, year = {2014}, abstract = {In this work the potential of polarimetric Synthetic Aperture Radar (PolSAR) data of dual-polarized TerraSAR-X (HH/VV) and quad-polarized Radarsat-2 was examined in combination with multispectral Landsat 8 data for unsupervised and supervised classification of tundra land cover types of Richards Island, Canada. The classification accuracies as well as the backscatter and reflectance characteristics were analyzed using reference data collected during three field work campaigns and include in situ data and high resolution airborne photography. The optical data offered an acceptable initial accuracy for the land cover classification. The overall accuracy was increased by the combination of PolSAR and optical data and was up to 71\% for unsupervised (Landsat 8 and TerraSAR-X) and up to 87\% for supervised classification (Landsat 8 and Radarsat-2) for five tundra land cover types. The decomposition features of the dual and quad-polarized data showed a high sensitivity for the non-vegetated substrate (dominant surface scattering) and wetland vegetation (dominant double bounce and volume scattering). These classes had high potential to be automatically detected with unsupervised classification techniques.}, language = {en} } @article{RauschenbergerSchmittAzeemetal.2019, author = {Rauschenberger, Tabea and Schmitt, Viola and Azeem, Muhammad and Klein-Hessling, Stefan and Murti, Krisna and Gr{\"a}n, Franziska and Goebeler, Matthias and Kerstan, Andreas and Klein, Matthias and Bopp, Tobias and Serfling, Edgar and Muhammad, Khalid}, title = {T cells control chemokine secretion by keratinocytes}, series = {Frontiers in Immunology}, volume = {10}, journal = {Frontiers in Immunology}, number = {1917}, issn = {1664-3224}, doi = {10.3389/fimmu.2019.01917}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195695}, year = {2019}, abstract = {The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8\(^+\)T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8\(^+\)T cells. One key molecule is IFN-γ that is synthesized by CD8\(^+\)T cells under the control of NFATc1 and NFATc2. CD8\(^+\)T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. In addition, CD8\(^+\)T cells induced numerous type I IFN-inducible "defense genes" in keratinocytes encoding the PD1 and CD40 ligands, TNF-α and caspase-1. The enhanced expression of type I IFN-inducible genes resembles the gene expression pattern at the dermal/epidermal interface in lichen planus, an inflammatory T lymphocyte-driven skin disease, in which we detected the expression of CXCL10 in keratinocytes in close vicinity to the infiltration front of T cells. These data reflect the multifaceted interplay of lymphocytes with keratinocytes at the molecular level.}, language = {en} } @article{CzyschMedina‐MontanoZhongetal.2022, author = {Czysch, Christian and Medina-Montano, Carolina and Zhong, Zifu and Fuchs, Alexander and Stickdorn, Judith and Winterwerber, Pia and Schmitt, Sascha and Deswarte, Kim and Raabe, Marco and Scherger, Maximilian and Combes, Francis and De Vrieze, Jana and Kasmi, Sabah and Sandners, Niek N. and Lienenklaus, Stefan and Koynov, Kaloian and R{\"a}der, Hans-Joachim and Lambrecht, Bart N. and David, Sunil A. and Bros, Matthias and Schild, Hansj{\"o}rg and Grabbe, Stephan and De Geest, Bruno G. and Nuhn, Lutz}, title = {Transient Lymph Node Immune Activation by Hydrolysable Polycarbonate Nanogels}, series = {Advanced Functional Materials}, volume = {32}, journal = {Advanced Functional Materials}, number = {35}, doi = {10.1002/adfm.202203490}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287255}, year = {2022}, abstract = {The development of controlled biodegradable materials is of fundamental importance in immunodrug delivery to spatiotemporally controlled immune stimulation but avoid systemic inflammatory side effects. Based on this, polycarbonate nanogels are developed as degradable micellar carriers for transient immunoactivation of lymph nodes. An imidazoquinoline-type TLR7/8 agonist is covalently conjugated via reactive ester chemistry to these nanocarriers. The nanogels not only provide access to complete disintegration by the hydrolysable polymer backbone, but also demonstrate a gradual disintegration within several days at physiological conditions (PBS, pH 6.4-7.4, 37 °C). These intrinsic properties limit the lifetime of the carriers but their payload can still be successfully leveraged for immunological studies in vitro on primary immune cells as well as in vivo. For the latter, a spatiotemporal control of immune cell activation in the draining lymph node is found after subcutaneous injection. Overall, these features render polycarbonate nanogels a promising delivery system for transient activation of the immune system in lymph nodes and may consequently become very attractive for further development toward vaccination or cancer immunotherapy. Due to the intrinsic biodegradability combined with the high chemical control during the manufacturing process, these polycarbonate-based nanogels may also be of great importance for clinical translation.}, language = {en} } @article{PoppSchmittBoehrerLangeretal.2021, author = {Popp, Sandy and Schmitt-B{\"o}hrer, Angelika and Langer, Simon and Hofmann, Ulrich and Hommers, Leif and Schuh, Kai and Frantz, Stefan and Lesch, Klaus-Peter and Frey, Anna}, title = {5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction}, series = {Journal of Clinical Medicine}, volume = {10}, journal = {Journal of Clinical Medicine}, number = {14}, issn = {2077-0383}, doi = {10.3390/jcm10143104}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242739}, year = {2021}, abstract = {Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally na{\"i}ve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (-/-) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT-/- mice with infarct sizes >30\% experienced 100\% mortality, while 50\% of 5-HTT+/- and 37\% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30\%) 5-HTT-/- mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT-/- mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.}, language = {en} } @article{GrunzWenigKunzetal.2020, author = {Grunz, Jan-Peter and Wenig, Andreas Max and Kunz, Andreas Steven and Veyhl-Wichmann, Maike and Schmitt, Rainer and Gietzen, Carsten Herbert and Pennig, Lenhard and Herz, Stefan and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Gassenmaier, Tobias}, title = {3D cone-beam CT with a twin robotic x-ray system in elbow imaging: comparison of image quality to high-resolution multidetector CT}, series = {European Radiology Experimental}, volume = {4}, journal = {European Radiology Experimental}, doi = {10.1186/s41747-020-00177-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229877}, year = {2020}, abstract = {Background Elbow imaging is challenging with conventional multidetector computed tomography (MDCT), while cone-beam CT (CBCT) provides superior options. We compared intra-individually CBCT versus MDCT image quality in cadaveric elbows. Methods A twin robotic x-ray system with new CBCT mode and a high-resolution clinical MDCT were compared in 16 cadaveric elbows. Both systems were operated with a dedicated low-dose (LD) protocol (equivalent volume CT dose index [CTDI\(_{vol(16 cm)}\)] = 3.3 mGy) and a regular clinical scan dose (RD) protocol (CTDI\(_{vol(16 cm)}\) = 13.8 mGy). Image quality was evaluated by two radiologists (R1 and R2) on a seven-point Likert scale, and estimation of signal intensity in cancellous bone was conducted. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) statistics were used. Results The CBCT prototype provided superior subjective image quality compared to MDCT scans (for RD, p ≤ 0.004; for LD, p ≤ 0.001). Image quality was rated very good or excellent in 100\% of the cases by both readers for RD CBCT, 100\% (R1) and 93.8\% (R2) for LD CBCT, 62.6\% and 43.8\% for RD MDCT, and 0.0\% and 0.0\% for LD MDCT. Single-measure ICC was 0.95 (95\% confidence interval 0.91-0.97; p < 0.001). Software-based assessment supported subjective findings with less "undecided" pixels in CBCT than dose-equivalent MDCT (p < 0.001). No significant difference was found between LD CBCT and RD MDCT. Conclusions In cadaveric elbow studies, the tested cone-beam CT prototype delivered superior image quality compared to high-end multidetector CT and showed a potential for considerable dose reduction.}, language = {en} } @article{RechHueberFinzeletal.2016, author = {Rech, Juergen and Hueber, Axel J. and Finzel, Stephanie and Englbrecht, Matthias and Haschka, Judith and Manger, Bernhard and Kleyer, Arnd and Reiser, Michaela and Cobra, Jayme Fogagnolo and Figueiredo, Camille and Tony, Hans-Peter and Kleinert, Stefan and Wendler, Joerg and Schuch, Florian and Ronneberger, Monika and Feuchtenberger, Martin and Fleck, Martin and Manger, Karin and Ochs, Wolfgang and Schmitt-Haendle, Matthias and Lorenz, Hanns-Martin and Nuesslein, Hubert and Alten, Rieke and Henes, Joerg and Krueger, Klaus and Schett, Georg}, title = {Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment}, series = {Annals of the Rheumatic Diseases}, volume = {75}, journal = {Annals of the Rheumatic Diseases}, number = {9}, doi = {10.1136/annrheumdis-2015-207900}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187519}, pages = {1637-1644}, year = {2016}, abstract = {Objective To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. Methods MBDA scores (scale 1-100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. Results Moderate-to-high MBDA scores were found in 33\% of patients with RA overall. Twice as many patients who relapsed (58\%) had moderate/high MBDA compared with patients who remained in remission (21\%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13\%) in patients who were MBDA-/ACPA-, moderate in patients who were MBDA+/ACPA- (33.3\%) and MBDA-ACPA+ (31.8\%) and high in patients who were MBDA+/ACPA+ (76.4\%). Conclusions MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80\% of the patients. Trial registration number EudraCT 2009-015740-42.}, language = {en} } @article{StephanTascilarYalcinMutluetal.2023, author = {Stephan, Marlene and Tascilar, Koray and Yalcin-Mutlu, Melek and Hagen, Melanie and Haschka, Judith and Reiser, Michaela and Hartmann, Fabian and Kleyer, Arnd and Hueber, Axel J. and Manger, Bernhard and Figueiredo, Camille and Cobra, Jayme Fogagnolo and Tony, Hans-Peter and Finzel, Stephanie and Kleinert, Stefan and Wendler, J{\"o}rg and Schuch, Florian and Ronneberger, Monika and Feuchtenberger, Martin and Fleck, Martin and Manger, Karin and Ochs, Wolfgang and Schmitt-Haendle, Matthias and Lorenz, Hannes Martin and N{\"u}sslein, Hubert and Alten, Rieke and Henes, Joerg and Kr{\"u}ger, Klaus and Schett, Georg and Rech, J{\"u}rgen}, title = {Physical function of RA patients tapering treatment — a post hoc analysis of the randomized controlled RETRO trial}, series = {Journal of Clinical Medicine}, volume = {12}, journal = {Journal of Clinical Medicine}, number = {11}, issn = {2077-0383}, doi = {10.3390/jcm12113723}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319349}, year = {2023}, abstract = {Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a post hoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50\% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, and taper/stop) as the predictor. Two-hundred and eighty-two patients were analyzed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that the decline in functionality according to HAQ after tapering or discontinuation of DMARDs in RA patients with stable remission is associated with recurrence, but not with an overall functional decline.}, language = {en} } @article{ElsnerKunzWagneretal.2023, author = {Elsner, Clara and Kunz, Andreas Steven and Wagner, Nicole and Huflage, Henner and H{\"u}bner, Stefan and Luetkens, Karsten Sebastian and Bley, Thorsten Alexander and Schmitt, Rainer and Erg{\"u}n, S{\"u}leyman and Grunz, Jan-Peter}, title = {MRI-based evaluation of the flexor digitorum superficialis anatomy: investigating the prevalence and morphometry of the "chiasma antebrachii"}, series = {Diagnostics}, volume = {13}, journal = {Diagnostics}, number = {14}, issn = {2075-4418}, doi = {10.3390/diagnostics13142406}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362631}, year = {2023}, abstract = {Recent dissection studies resulted in the introduction of the term "chiasma antebrachii", which represents an intersection of the flexor digitorum superficialis (FDS) tendons for digits 2 and 3 in the distal third of the forearm. This retrospective investigation aimed to provide an MRI-based morphologic analysis of the chiasma antebrachii. In 89 patients (41 women, 39.3 ± 21.3 years), MRI examinations of the forearm (2010-2021) were reviewed by two radiologists, who evaluated all studies for the presence and length of the chiasma as well as its distance from the distal radioulnar and elbow joint. The chiasma antebrachii was identified in the distal third of the forearm in 88 patients (98.9\%), while one intersection was located more proximally in the middle part. The chiasma had a median length of 28 mm (interquartile range: 24-35 mm). Its distances to the distal radioulnar and elbow joint were 16 mm (8-25 mm) and 215 mm (187-227 mm), respectively. T1-weighted post-contrast sequences were found to be superior to T2- or proton-density-weighted sequences in 71 cases (79.8\%). To conclude, the chiasma antebrachii is part of the standard FDS anatomy. Knowledge of its morphology is important, e.g., in targeted injections of therapeutics or reconstructive surgery.}, language = {en} }