@article{SellmerStanglBeyeretal., author = {Sellmer, Andreas and Stangl, Hubert and Beyer, Mandy and Gr{\"u}nstein, Elisabeth and Leonhardt, Michel and Pongratz, Herwig and Eichhorn, Emerich and Elz, Sigurd and Striegl, Birgit and Jenei-Lanzl, Zsuzsa and Dove, Stefan and Straub, Rainer H. and Kr{\"a}mer, Oliver H. and Mahboobi, Siavosh}, title = {Marbostat-100 Defines a New Class of Potent and Selective Antiinflammatory and Antirheumatic Histone Deacetylase 6 Inhibitors}, series = {Journal of medicinal chemistry}, volume = {61}, journal = {Journal of medicinal chemistry}, number = {8}, publisher = {ACS Publications}, doi = {10.1021/acs.jmedchem.7b01593}, pages = {3454 -- 3477}, abstract = {Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to autoimmunity, cancer, HIV infection, inflammation, and neurodegeneration. Hence, histone deacetylase inhibitors (HDACi), which alter protein acetylation, gene expression patterns, and cell fate decisions, represent promising new drugs for the therapy of these diseases. Whereas pan-HDACi inhibit all 11 Zn2+-dependent histone deacetylases (HDACs) and cause a broad spectrum of side effects, specific inhibitors of histone deacetylase 6 (HDAC6i) are supposed to have less side effects. We present the synthesis and biological evaluation of Marbostats, novel HDAC6i that contain the hydroxamic acid moiety linked to tetrahydro-β-carboline derivatives. Our lead compound Marbostat-100 is a more potent and more selective HDAC6i than previously established well-characterized compounds in vitro as well as in cells. Moreover, Marbostat-100 is well tolerated by mice and effective against collagen type II induced arthritis. Thus, Marbostat-100 represents a most selective known HDAC6i and the possibility for clinical evaluation of a HDAC isoform-specific drug.}, language = {en} } @misc{BaldaranovKilicPflugetal., author = {Baldaranov, Dobri and Kilic, Mustafa and Pflug, Kenny and Theiss, Stephan and Leis, Alexander and Pemmerl, Josef and Pels, Hendrik and Boy, Sandra and Bogdahn, Ulrich and Schlachetzki, Felix}, title = {Prehospital stroke education in paramedics}, series = {European Journal of Neurology}, volume = {22}, journal = {European Journal of Neurology}, number = {Suppl. 1}, publisher = {Wiley}, pages = {800}, abstract = {Background and aims: Rapid pre-hospital identification of stroke symptoms result in therapy directed admission to dedicated stroke units. Widespread application of stroke scales reveal high sensitivity but low specificity, especially in non-academic first aid personal. In our previous work we show that prehospital stroke diagnostics based on neurolo-gical examination and transcranial color-coded Duplex so-nography (TCCS) is feasible and results in high sensitivity and specificity for middle cerebral artery / distal internal carotid artery occlusion. The aim of our ongoing study is to design and evaluate a dedicated stroke educational program for paramedics including transcranial ultrasound. This is a prerequisite for a telemedical decision support system in the absence of stroke experienced emergency doctors. Methods: We currently educate 6 paramedics in advanced stroke neurology and also transcranial ultrasound examina-tion during a course of 2 months. The web-based curricu-lum was designed in two parts. The first was theoretical and the second will be the real-life training under neurological supervision. For final assessment of the theoretical know-ledge a control group will be implemented without specific stroke expertise. The stroke-educated paramedics will have to assist stroke investigation, perform pre-hospital TCCS and enter the date in a mobile telestroke pad. The data set will be send to an in-hospital stroke physician. We will as-sess the mean time to reach the diagnostic assessment, its sensitivity and specificity and the patient outcome after 30 days. Results: Our study is ongoing Conclusion: The study just reach the 2 part and we will be glad to present our data on the meeting EAN 2015. Disclosure: Nothing to disclose}, language = {en} } @article{WidbillerKeimSchlichtingetal., author = {Widbiller, Matthias and Keim, Lukas and Schlichting, Ralf and Striegl, Birgit and Hiller, Karl-Anton and Jungbauer, Rebecca and Buchalla, Wolfgang and Galler, Kerstin M.}, title = {Debris Removal by Activation of Endodontic Irrigants in Complex Root Canal Systems}, series = {Applied Sciences}, volume = {11}, journal = {Applied Sciences}, number = {16}, publisher = {MDPI}, address = {Basel}, doi = {10.3390/app11167331}, pages = {1 -- 14}, abstract = {Aim of the study was to develop a standardized model system to investigate endodontic irrigation techniques and assess the efficiency of different activation methods on the removal of hard tissue debris in complex root canal systems. Mesial roots of mandibular molars were firstly scanned by micro-computed tomography (µCT) and allocated to three groups of irrigant activation: sonic activation (EDDY, VDW, Munich, Germany), laser activation (AutoSWEEPS, FOTONA, Ljubljana, Slovenia) and conventional needle irrigation (control). Roots were fixed in individual 3D-printed holders to facilitate root canal enlargement under constant irrigation with NaOCl (5\%). To enable standardized quantification of remaining debris, BaSO4-enriched dentine powder was compacted into the canals, followed by another µCT-scan. The final irrigation was performed using 17\% ethylenediaminetetraacetic acid (EDTA) and 5\% sodium hypochlorite (NaOCl) with the respective activation method, and the volume of remaining artificial debris was quantified after a final µCT-scan. The newly developed model system allowed for reliable, reproducible and standardized assessment of irrigation methods. Activation of the irrigant proved to be significantly more effective than conventional needle irrigation regarding the removal of debris, which persisted particularly in the apical third of the root canal in the control group. The efficiency of irrigation was significantly enhanced with laser- and sonic-based activation, especially in the apical third.}, language = {en} } @article{HuberSchlosserStenzeletal., author = {Huber, Michaela and Schlosser, Daniela and Stenzel, Susanne and Maier, Johannes and Pattappa, Girish and Kujat, Richard and Striegl, Birgit and Docheva, Denitsa}, title = {Quantitative Analysis of Surface Contouring with Pulsed Bipolar Radiofrequency on Thin Chondromalacic Cartilage}, series = {BioMed Research International}, journal = {BioMed Research International}, publisher = {HINDAWI}, doi = {10.1155/2020/1242086}, pages = {1 -- 8}, abstract = {The purpose of this study was to evaluate the quality of surface contouring of chondromalacic cartilage by bipolar radio frequency energy using different treatment patterns in an animal model, as well as examining the impact of the treatment onto chondrocyte viability by two different methods. Our experiments were conducted on 36 fresh osteochondral sections from the tibia plateau of slaughtered 6-month-old pigs, where the thickness of the cartilage is similar to that of human wrist cartilage. An area of 1 cm(2) was first treated with emery paper to simulate the chondromalacic cartilage. Then, the treatment with RFE followed in 6 different patterns. The osteochondral sections were assessed for cellular viability (live/dead assay, caspase (cell apoptosis marker) staining, and quantitative analysed images obtained by fluorescent microscopy). For a quantitative characterization of none or treated cartilage surfaces, various roughness parameters were measured using confocal laser scanning microscopy (Olympus LEXT OLS 4000 3D). To describe the roughness, the Root-Mean-Square parameter (Sq) was calculated. A smoothing effect of the cartilage surface was detectable upon each pattern of RFE treatment. The Sq for native cartilage was Sq=3.8 +/- 1.1 mu m. The best smoothing pattern was seen for two RFE passes and a 2-second pulsed mode (B2p2) with an Sq=27.3 +/- 4.9 mu m. However, with increased smoothing, an augmentation in chondrocyte death up to 95\% was detected. Using bipolar RFE treatment in arthroscopy for small joints like the wrist or MCP joints should be used with caution. In the case of chondroplasty, there is a high chance to destroy the joint cartilage.}, language = {en} } @article{SchroederPolzerSlažanskyetal., author = {Schroeder, Florian and Polzer, Stanislav and Slažansk{\´y}, Martin and Man, Vojtěch and Sk{\´a}cel, Pavel}, title = {Predictive capabilities of various constitutive models for arterial tissue}, series = {Journal of the Mechanical Behavior of Biomedical Materials}, volume = {78}, journal = {Journal of the Mechanical Behavior of Biomedical Materials}, number = {February}, publisher = {Elsevier}, doi = {10.1016/j.jmbbm.2017.11.035}, pages = {369 -- 380}, abstract = {Introduction Aim of this study is to validate some constitutive models by assessing their capabilities in describing and predicting uniaxial and biaxial behavior of porcine aortic tissue. Methods 14 samples from porcine aortas were used to perform 2 uniaxial and 5 biaxial tensile tests. Transversal strains were furthermore stored for uniaxial data. The experimental data were fitted by four constitutive models: Holzapfel-Gasser-Ogden model (HGO), model based on generalized structure tensor (GST), Four-Fiber-Family model (FFF) and Microfiber model. Fitting was performed to uniaxial and biaxial data sets separately and descriptive capabilities of the models were compared. Their predictive capabilities were assessed in two ways. Firstly each model was fitted to biaxial data and its accuracy (in term of R2 and NRMSE) in prediction of both uniaxial responses was evaluated. Then this procedure was performed conversely: each model was fitted to both uniaxial tests and its accuracy in prediction of 5 biaxial responses was observed. Results Descriptive capabilities of all models were excellent. In predicting uniaxial response from biaxial data, microfiber model was the most accurate while the other models showed also reasonable accuracy. Microfiber and FFF models were capable to reasonably predict biaxial responses from uniaxial data while HGO and GST models failed completely in this task. Conclusions HGO and GST models are not capable to predict biaxial arterial wall behavior while FFF model is the most robust of the investigated constitutive models. Knowledge of transversal strains in uniaxial tests improves robustness of constitutive models.}, language = {en} } @inproceedings{GeithSommerSchratzenstalleretal., author = {Geith, Markus A. and Sommer, Gerhard and Schratzenstaller, Thomas and Holzapfel, Gerhard A.}, title = {First Approaches in Quantifying Acute Vascular Damage due to Stenting}, series = {23rd Congress of the European Society of Biomechanics, July 2-5,2017, Seville, Spain}, booktitle = {23rd Congress of the European Society of Biomechanics, July 2-5,2017, Seville, Spain}, subject = {Stent}, language = {en} } @article{GeithEckmannHaspingeretal., author = {Geith, Markus A. and Eckmann, Jakob D. and Haspinger, Daniel Ch. and Agrafiotis, Emmanouil and Maier, Dominik and Szabo, Patrick and Sommer, Gerhard and Schratzenstaller, Thomas and Holzapfel, Gerhard A.}, title = {Experimental and mathematical characterization of coronary polyamide-12 balloon catheter membranes}, series = {PLoS One}, volume = {15}, journal = {PLoS One}, number = {6}, publisher = {PLOS}, doi = {10.1371/journal.pone.0234340}, pages = {1 -- 22}, abstract = {The experimental quantification and modeling of the multiaxial mechanical response of polymer membranes of coronary balloon catheters have not yet been carried out. Due to the lack of insights, it is not shown whether isotropic material models can describe the material response of balloon catheter membranes expanded with nominal or higher, supra-nominal pressures. Therefore, for the first time, specimens of commercial polyamide-12 balloon catheters membranes were investigated during uniaxial and biaxial loading scenarios. Furthermore, the influence of kinematic effects on the material response was observed by comparing results from quasi-static and dynamic biaxial extension tests. Novel clamping techniques are described, which allow to test even tiny specimens taken from the balloon membranes. The results of this study reveal the semi-compliant, nonlinear, and viscoelastic character of polyamide-12 balloon catheter membranes. Above nominal pressure, the membranes show a pronounced anisotropic mechanical behavior with a stiffer response in the circumferential direction. The anisotropic feature intensifies with an increasing strain-rate. A modified polynomial model was applied to represent the realistic mechanical response of the balloon catheter membranes during dynamic biaxial extension tests. This study also includes a compact set of constitutive model parameters for the use of the proposed model in future finite element analyses to perform more accurate simulations of expanding balloon catheters.}, language = {en} } @article{GeithSwidergalHochholdingeretal., author = {Geith, Markus A. and Swidergal, Krzysztof and Hochholdinger, Bernd and Schratzenstaller, Thomas and Wagner, Marcus and Holzapfel, Gerhard A.}, title = {On the importance of modeling balloon folding, pleating, and stent crimping: An FE study comparing experimental inflation tests}, series = {International Journal for Numerical Methods in Biomedical Engineering}, volume = {35}, journal = {International Journal for Numerical Methods in Biomedical Engineering}, number = {11}, publisher = {Wiley}, doi = {10.1002/cnm.3249}, abstract = {Finite element (FE)-based studies of preoperative processes such as folding,pleating, and stent crimping with a comparison with experimental inflation tests are not yet available. Therefore, a novel workflow is presented in which residual stresses of balloon folding and pleating, as well as stent crimping, and the geometries of all contact partners were ultimately implemented in an FE code to simulate stent expansion by using an implicit solver. The numerical results demonstrate that the incorporation of residual stresses and strains experienced during the production step significantly increased the accuracy of the subsequent simulations, especially of the stent expansion model. During the preoperative processes, stresses inside the membrane and the stent material also reached a rather high level. Hence, there can be no presumption that balloon catheters or stents are undamaged before the actual surgery. The implementation of the realistic geometry, in particular the balloon tapers, and the blades of the process devices improved the simulation of the expansion mech-anisms, such as dogboning, concave bending, or overexpansion of stent cells. This study shows that implicit solvers are able to precisely simulate the mentioned preoperative processes and the stent expansion procedure without a preceding manipulation of the simulation time or physical mass.}, subject = {Stent}, language = {en} } @inproceedings{DendorferFeldottoWalchetal., author = {Dendorfer, Sebastian and Feldotto, Benedikt and Walch, Blasius and Koch, Patrick and Knoll, Alois}, title = {Co-Development of an Infant Prototype in Hardware and Simulation based on CT Imaging Data}, series = {IEEE International Conference on Cyborg and Bionic Systems (CBS), 2019, Munich}, booktitle = {IEEE International Conference on Cyborg and Bionic Systems (CBS), 2019, Munich}, pages = {6}, abstract = {The development of biomimetic robots has gained research interest in the last years as it may both help under-standing processes of motion execution in biological systems as well as developping a novel generation of intelligent and energy efficient robots. However, exact model generation that builds up on observations and robot design is very time intensive. In this paper we present a novel pipeline for co-development of biomimetic hardware and simulation models based on biological Computer Tomography (CT) data. For this purpose we exploit State of the Art rapid prototyping technologies such as 3D Printing and the Neurorobotics Platform for musculoskeletal simulations in virtual environments. The co-development integrates both advantages of virtual and physical experimental models and is expected to increase development speed of controllers that can be tested on the simulated counterpart before application to a printed robot model. We demonstrate the pipeline by generating a one year old infant model as a musculoskeletal simulation model and a print-in-place 3D printed skeleton as a single movable part. Even though we hereonly introduce the initial body generation and only a first testsetup for a modular sensory and control framework, we can clearly spot advantages in terms of rapid model generation and highly biological related models. Engineering costs are reducedand models can be provided to a wide research community for controller testing in an early development phase.}, subject = {Biomechanische Analyse}, language = {en} } @article{WeberDendorferBulstraetal., author = {Weber, Tim A. and Dendorfer, Sebastian and Bulstra, Sjoerd K. and Grifka, Joachim and Verkerke, Gijsbertus Jacob and Renkawitz, Tobias}, title = {Gait six month and one-year after computer assisted Femur First THR vs. conventional THR. Results of a patient- and observer- blinded randomized controlled trial}, series = {Gait \& Posture}, volume = {vol. 49}, journal = {Gait \& Posture}, doi = {10.1016/j.gaitpost.2016.06.035}, pages = {418 -- 425}, abstract = {A prospective randomized controlled trial is presented that is used to compare gait performance between the computer assisted Femur First (CAS FF) operation method and conventional THR (CON). 60 patients underwent a 3D gait analysis of the lower extremity at pre-operative, 6 months post-operative and twelve months post-operative. Detailed verification experiments were facilitated to ensure the quality of data as well as to avoid over-interpreting of the data. The results confirm a similar data-quality as reported in the literature. Walking speed, range of motion and symmetry thereof improved over the follow-up period, without significant differences between the groups. While all parameters do significantly increase over the follow-up period for both groups, there were no significant differences between them at any given time-point. Patients undergoing CAS FF showed a trend to improved hip flexion angle indicating a possible long-term benefit.}, language = {en} }