TY - JOUR A1 - Temiz Artmann, Aysegül A1 - Kurulgan demirci, Eylem A1 - Fırat, Ipek Seda A1 - Oflaz, Hakan A1 - Artmann, Gerhard T1 - Recombinant activated protein C (rhAPC) affects lipopolysaccharide-induced mechanical compliance changes and beat frequency of mESC-derived cardiomyocyte monolayers JF - SHOCK KW - Septic cardiomyopathy KW - LPS KW - cardiomyocyte biomechanics KW - CellDrum KW - actin cytoskeleton Y1 - 2021 U6 - https://doi.org/10.1097/SHK.0000000000001845 SN - 1540-0514 PB - Wolters Kluwer CY - Köln ER - TY - JOUR A1 - Goßmann, Matthias A1 - Frotscher, Ralf A1 - Linder, Peter A1 - Bayer, Robin A1 - Epple, U. A1 - Staat, Manfred A1 - Temiz Artmann, Aysegül A1 - Artmann, Gerhard T1 - Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells JF - Cellular physiology and biochemistry N2 - Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential. KW - Inotropic compounds KW - Pharmacology KW - Ion channels KW - CellDrum KW - Heart tissue culture KW - Induced pluripotent stem cells KW - Cardiac myocytes Y1 - 2016 U6 - https://doi.org/10.1159/000443124 SN - 1421-9778 (Online) SN - 1015-8987 (Print) VL - 38 IS - 3 SP - 1182 EP - 1198 PB - Karger CY - Basel ER - TY - JOUR A1 - Arinkin, Vladimir A1 - Digel, Ilya A1 - Porst, Dariusz A1 - Temiz Artmann, Aysegül A1 - Artmann, Gerhard T1 - Phenotyping date palm varieties via leaflet cross-sectional imaging and artificial neural network application JF - BMC bioinformatics N2 - Background True date palms (Phoenix dactylifera L.) are impressive trees and have served as an indispensable source of food for mankind in tropical and subtropical countries for centuries. The aim of this study is to differentiate date palm tree varieties by analysing leaflet cross sections with technical/optical methods and artificial neural networks (ANN). Results Fluorescence microscopy images of leaflet cross sections have been taken from a set of five date palm tree cultivars (Hewlat al Jouf, Khlas, Nabot Soltan, Shishi, Um Raheem). After features extraction from images, the obtained data have been fed in a multilayer perceptron ANN with backpropagation learning algorithm. Conclusions Overall, an accurate result in prediction and differentiation of date palm tree cultivars was achieved with average prediction in tenfold cross-validation is 89.1% and reached 100% in one of the best ANN. Y1 - 2014 U6 - https://doi.org/10.1186/1471-2105-15-55 SN - 1471-2105 VL - 15 IS - 55 SP - 1 EP - 8 ER - TY - JOUR A1 - Micili, Serap C. A1 - Valter, Markus A1 - Oflaz, Hakan A1 - Ozogul, Candan A1 - Linder, Peter A1 - Föckler, Nicole A1 - Artmann, Gerhard A1 - Digel, Ilya A1 - Temiz Artmann, Aysegül T1 - Optical coherence tomography : a potential tool to predict premature rupture of fetal membranes JF - Proceedings of the Institution of Mechanical Engineers. Part H : Journal of engineering in medicine Y1 - 2013 SN - 0046-2039 (Print) ; 2041-3033 (E-Journal) VL - Vol. 227 IS - No. 4 SP - 393 EP - 401 PB - Sage CY - London ER - TY - JOUR A1 - Kurulgan Demirci, Eylem A1 - Demirci, Taylan A1 - Linder, Peter A1 - Trzewik, Jürgen A1 - Gierkowski, Jessica Ricarda A1 - Gossmann, Matthias A1 - Kayser, Peter A1 - Porst, Dariusz A1 - Digel, Ilya A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül T1 - rhAPC reduces the endothelial cell permeability via a decrease of contractile tensions induced by endothelial cells JF - Journal of Bioscience and Bioengineering N2 - All cells generate contractile tension. This strain is crucial for mechanically controlling the cell shape, function and survival. In this study, the CellDrum technology quantifying cell's (the cellular) mechanical tension on a pico-scale was used to investigate the effect of lipopolysaccharide (LPS) on human aortic endothelial cell (HAoEC) tension. The LPS effect during gram-negative sepsis on endothelial cells is cell contraction causing endothelium permeability increase. The aim was to finding out whether recombinant activated protein C (rhAPC) would reverse the endothelial cell response in an in-vitro sepsis model. In this study, the established in-vitro sepsis model was confirmed by interleukin 6 (IL-6) levels at the proteomic and genomic levels by ELISA, real time-PCR and reactive oxygen species (ROS) activation by florescence staining. The thrombin cellular contraction effect on endothelial cells was used as a positive control when the CellDrum technology was applied. Additionally, the Ras homolog gene family, member A (RhoA) mRNA expression level was checked by real time-PCR to support contractile tension results. According to contractile tension results, the mechanical predominance of actin stress fibers was a reason of the increased endothelial contractile tension leading to enhanced endothelium contractility and thus permeability enhancement. The originality of this data supports firstly the basic measurement principles of the CellDrum technology and secondly that rhAPC has a beneficial effect on sepsis influenced cellular tension. The technology presented here is promising for future high-throughput cellular tension analysis that will help identify pathological contractile tension responses of cells and prove further cell in-vitro models. KW - Cell permeability KW - Cellular force KW - Endothelial cells KW - Recombinant activated protein C KW - Lipopolysaccharide KW - Contractile tension KW - CellDrum Y1 - 2012 U6 - https://doi.org/10.1016/j.jbiosc.2012.03.019 SN - 1347-4421 VL - 113 IS - 2 SP - 212 EP - 219 PB - Elsevier CY - Amsterdam ER - TY - BOOK A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül A1 - Zhubanova, Azhar A. A1 - Digel, Ilya ED - Artmann, Gerhard ED - Temiz Artmann, Aysegül ED - Zhubanova, Azhar A. ED - Digel, Ilya T1 - Biological, physical and technical basics of cell engineering Y1 - 2018 SN - 978-981-10-7903-0 PB - Springer CY - Singapore ER - TY - JOUR A1 - Angermann, Susanne A1 - Günthner, Roman A1 - Hanssen, Henner A1 - Lorenz, Georg A1 - Braunisch, Matthias C. A1 - Steubl, Dominik A1 - Matschkal, Julia A1 - Kemmner, Stephan A1 - Hausinger, Renate A1 - Block, Zenonas A1 - Haller, Bernhard A1 - Heemann, Uwe A1 - Kotliar, Konstantin A1 - Grimmer, Timo A1 - Schmaderer, Christoph T1 - Cognitive impairment and microvascular function in end-stage renal disease JF - International Journal of Methods in Psychiatric Research (MPR) N2 - Objective Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age-matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels. Methods 152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions. Results In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained. Conclusion This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention. KW - cerebral small vessel disease KW - cognitive impairment KW - dialysis KW - retinal vessels Y1 - 2022 U6 - https://doi.org/10.1002/mpr.1909 SN - 1049-8931 (Print) SN - 1557-0657 (Online) VL - 31 IS - 2 SP - 1 EP - 10 PB - Wiley ER - TY - JOUR A1 - Kotliar, Konstantin A1 - Ortner, Marion A1 - Conradi, Anna A1 - Hacker, Patricia A1 - Hauser, Christine A1 - Günthner, Roman A1 - Moser, Michaela A1 - Muggenthaler, Claudia A1 - Diehl-Schmid, Janine A1 - Priller, Josef A1 - Schmaderer, Christoph A1 - Grimmer, Timo T1 - Altered retinal cerebral vessel oscillation frequencies in Alzheimer's disease compatible with impaired amyloid clearance JF - Neurobiology of Aging N2 - Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis. KW - Alzheimer's disease KW - Retinal vessel analysis KW - Vasomotions KW - Pulsations KW - Mild cognitive impairment Y1 - 2022 U6 - https://doi.org/10.1016/j.neurobiolaging.2022.08.012 SN - 0197-4580 VL - 120 SP - 117 EP - 127 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Neumaier, Felix A1 - Weiss, Miriam A1 - Veldeman, Michael A1 - Kotliar, Konstantin A1 - Wiesmann, Martin A1 - Schulze-Steinen, Henna A1 - Höllig, Anke A1 - Clusmann, Hans A1 - Schubert, Gerrit Alexander A1 - Albanna, Walid T1 - Changes in endogenous daytime melatonin levels after aneurysmal subarachnoid hemorrhage – preliminary findings from an observational cohort study JF - Clinical Neurology and Neurosurgery N2 - Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH. KW - constructive alignment KW - examination KW - long-term retention KW - multimodal KW - practical learning Y1 - 2021 U6 - https://doi.org/10.1016/j.clineuro.2021.106870 SN - 0303-8467 VL - 208 IS - Article No.: 106870 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Alnemer, Momin Sami Mohammad A1 - Kotliar, Konstantin A1 - Neuhaus, Valentin A1 - Pape, Hans-Christoph A1 - Ciritsis, Bernhard D. T1 - Cost-effectiveness analysis of surgical proximal femur fracture prevention in elderly: a Markov cohort simulation model JF - Cost Effectiveness and Resource Allocation N2 - Background Hip fractures are a common and costly health problem, resulting in significant morbidity and mortality, as well as high costs for healthcare systems, especially for the elderly. Implementing surgical preventive strategies has the potential to improve the quality of life and reduce the burden on healthcare resources, particularly in the long term. However, there are currently limited guidelines for standardizing hip fracture prophylaxis practices. Methods This study used a cost-effectiveness analysis with a finite-state Markov model and cohort simulation to evaluate the primary and secondary surgical prevention of hip fractures in the elderly. Patients aged 60 to 90 years were simulated in two different models (A and B) to assess prevention at different levels. Model A assumed prophylaxis was performed during the fracture operation on the contralateral side, while Model B included individuals with high fracture risk factors. Costs were obtained from the Centers for Medicare & Medicaid Services, and transition probabilities and health state utilities were derived from available literature. The baseline assumption was a 10% reduction in fracture risk after prophylaxis. A sensitivity analysis was also conducted to assess the reliability and variability of the results. Results With a 10% fracture risk reduction, model A costs between $8,850 and $46,940 per quality-adjusted life-year ($/QALY). Additionally, it proved most cost-effective in the age range between 61 and 81 years. The sensitivity analysis established that a reduction of ≥ 2.8% is needed for prophylaxis to be definitely cost-effective. The cost-effectiveness at the secondary prevention level was most sensitive to the cost of the contralateral side’s prophylaxis, the patient’s age, and fracture treatment cost. For high-risk patients with no fracture history, the cost-effectiveness of a preventive strategy depends on their risk profile. In the baseline analysis, the incremental cost-effectiveness ratio at the primary prevention level varied between $11,000/QALY and $74,000/QALY, which is below the defined willingness to pay threshold. Conclusion Due to the high cost of hip fracture treatment and its increased morbidity, surgical prophylaxis strategies have demonstrated that they can significantly relieve the healthcare system. Various key assumptions facilitated the modeling, allowing for adequate room for uncertainty. Further research is needed to evaluate health-state-associated risks. KW - Hip fractures KW - Prevention KW - Geriatric KW - Cost-effectiveness KW - Prophylaxis Y1 - 2023 U6 - https://doi.org/10.1186/s12962-023-00482-4 SN - 1478-7547 N1 - Corresponding author: Momin S. Alnemer IS - 21, Article number: 77 PB - Springer Nature ER -