TY - JOUR A1 - Sellmer, Andreas A1 - Stangl, Hubert A1 - Beyer, Mandy A1 - Grünstein, Elisabeth A1 - Leonhardt, Michel A1 - Pongratz, Herwig A1 - Eichhorn, Emerich A1 - Elz, Sigurd A1 - Striegl, Birgit A1 - Jenei-Lanzl, Zsuzsa A1 - Dove, Stefan A1 - Straub, Rainer H. A1 - Krämer, Oliver H. A1 - Mahboobi, Siavosh T1 - Marbostat-100 Defines a New Class of Potent and Selective Antiinflammatory and Antirheumatic Histone Deacetylase 6 Inhibitors JF - Journal of medicinal chemistry N2 - 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. KW - Animals KW - anti-Inflammatory agent KW - chemical synthesis KW - pharmacology KW - therapeutic use KW - toxicity Y1 - 2018 U6 - https://doi.org/10.1021/acs.jmedchem.7b01593 VL - 61 IS - 8 SP - 3454 EP - 3477 PB - ACS Publications ER - TY - JOUR A1 - Schroeder, Florian A1 - Polzer, Stanislav A1 - Slažanský, Martin A1 - Man, Vojtěch A1 - Skácel, Pavel T1 - Predictive capabilities of various constitutive models for arterial tissue JF - Journal of the Mechanical Behavior of Biomedical Materials N2 - 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. KW - Arterial biomechanics KW - Constitutive modeling KW - Mechanical testing KW - Uniaxial – biaxial tension Y1 - 2018 U6 - https://doi.org/10.1016/j.jmbbm.2017.11.035 VL - 78 IS - February SP - 369 EP - 380 PB - Elsevier ER - TY - JOUR A1 - Schmitz, Paul A1 - Neumann, Christoph Cornelius A1 - Neumann, Carsten A1 - Nerlich, Michael A1 - Dendorfer, Sebastian T1 - Biomechanical analysis of iliac crest loading following cortico-cancellous bone harvesting JF - Journal of Orthopaedic Surgery and Research N2 - Background Iliac crest bone harvesting is a frequently performed surgical procedure widely used to treat bone defects. The objective of this study is to assess the biomechanical quantities related to risk for pelvic fracture after harvesting an autologous bone graft at the anterior iliac crest. Methods Finite element models with a simulated harvest site (sized 15 × 20 mm, 15 × 35 mm, 30 × 20 mm and 30 × 35 mm) in the iliac wing are created. The relevant loading case is when the ipsilateral leg is lifted off the ground. Musculoskeletal analysis is utilized to compute the muscle and joint forces involved in this motion. These forces are used as boundary conditions for the finite element analyses. Bone tissue stress is analyzed. Results Critical stress peaks are located between the anterior superior iliac spine (ASIS) and the anterior edge of the harvest site. Irrespective of the graft size, the iliac wing does not show any significant stress peaks with the harvest site being 20 to 25 mm posterior to the ASIS. The harvest area itself inhibits the distribution of the forces applied on the ASIS to extend to the posterior iliac wing. This leads to a lack of stress posterior to the harvest site. A balanced stress distribution with no stress peaks appears when the bone graft is taken below the iliac crest. Conclusion A harvest site located at least 20 to 25 mm posterior to the ASIS should be preferred to minimize the risk of iliac fatigue fracture. KW - Bone harvesting KW - Autologous bone graft KW - Iliac crest KW - Fatigue fracture KW - Pelvis KW - ASIS KW - FEA KW - Biomechanical investigation KW - Beckenkammknochen KW - Knochenentnahme KW - Spongiosa KW - Biomechanische Analyse Y1 - 2018 U6 - https://doi.org/10.1186/s13018-018-0822-1 VL - 13 IS - 108 SP - 1 EP - 8 PB - Springer Nature ER - TY - CHAP A1 - Aurbach, Maximilian A1 - Jungtäubl, Dominik A1 - Spicka, Jan A1 - Dendorfer, Sebastian T1 - EMG-based validation of musculoskeletal models considering crosstalk T2 - World Congress Biomechanics, 28-30 June 2018, Dublin N2 - BACKGROUND: Validation and verification of multibody musculoskeletal models sEMG is a difficult process because of the reliability of sEMG data and the complex relationship of muscle force and sEMG. OBJECTIVE: This work aims at comparing experimentally recorded and simulated muscle activities considering a numerical model for crosstalk. METHODS: For providing an experimentally derived reference data set, subjects were performing elevations of the arm, where the activities of the contemplated muscle groups were measured by sEMG sensors. Computed muscle activities were further processed and transformed into an artificial electromyographical signal, which includes a numerical crosstalk model. In order to determine whether the crosstalk model provides a better agreement with the measured muscle activities, the Pearson correlation coefficient has been computed as a qualitative way of assessing the curve progression of the data sets. RESULTS: The results show an improvement in the correlation coefficient between the experimental data and the simulated muscle activities when taking crosstalk into account. CONCLUSIONS: Although the correlation coefficient increased when the crosstalk model was utilized, it is questionable if the discretization of both, the crosstalk and the musculoskeletal model, is accurate enough. Y1 - 2018 U6 - https://doi.org/10.1109/BIOMDLORE.2018.8467211 ER - TY - GEN A1 - Singh, Max Diamond T1 - Zusätzliche Anforderungen an Produktdaten und technische Dokumentation durch die MDR T2 - Medizintechnik Kongress 2018: Effizienz in der Medizinprodukteentwicklung vor dem Hintergrund von MDR und IVDR ; Frankfurt am Main, 08.11.2018, [Veranstalter: Velten Consulting & ILC Consulting] Y1 - 2018 ER - TY - GEN A1 - Singh, Max Diamond T1 - Notified Body Viewpoint : Preparing for MDR/IVDR T2 - MDR/IVDR - Status Report from Stakeholders. Where are we now in November 2018? - Bern, 22.11.2018 - [Veranstalter: RAPS : Regulatory Affairs Professionals Society] Y1 - 2018 ER - TY - GEN A1 - Singh, Max Diamond T1 - Overview of the Medical Device Regulation (MDR) BT - MDR-Roadshow TÜV SÜD MHS, San Diego & Minneapolis, 2018 Y1 - 2018 ER - TY - JOUR A1 - Raptis, Georgios T1 - Technischer Datenschutz in der telemedizinischen Versorgung JF - Der Krankenhaus-JUSTITIAR N2 - Die fortschreitende Digitalisierung des Gesundheitswesens ebnet auch den Weg einer stärkeren Verbreitung der telemedizinischen Versorgung in Deutschland. Die Politik erleichtert diesen Weg, z.B. mit dem eHealth-Gesetz oder mit der Lockerung des "Fernbehandlungsverbots" durch den Deutschen Ärztetag. Dabei wird schon aus der Definition (siehe z.B. die unten stehende Definition der AG Telemedizin) klar, dass Telemedizin keine neue medizinische Disziplin begründet. Bei Telemedizin handelt es sich nur um ein technisches Werkzeug in Kombination mit geeigneten klinischen Prozessen, damit bestehende medizinische Expertise unter Einsatz von Informations- und Kommunikationstechnologien räumliche Entfernungen oder einen zeitlichen Versatz überbrücken kann. Patientinnen und Patienten können also behandelt werden, auch wenn sie vom Arzt räumlich entfernt sind. KW - Telemedizin KW - Datenschutz Y1 - 2018 VL - 7 IS - 4 SP - 105 EP - 107 ER - TY - JOUR A1 - Benditz, Achim A1 - Auer, Simon A1 - Spörrer, J.F. A1 - Wolkerstorfer, S. A1 - Grifka, Joachim A1 - Süß, Franz A1 - Dendorfer, Sebastian T1 - Regarding loads after spinal fusion, every level should be seen separately: a musculoskeletal analysis JF - European Spine Journal N2 - The number of spinal fusion surgeries is steadily increasing and biomechanical consequences are still in debate. The aim of this study is to provide biomechanical insights into the sagittal balance of the spine and to compare spinal load before and after spinal fusion. METHOD: The joint reaction forces of 52 patients were analyzed in proximo-distal and antero-posterior direction from the levels T12-L1 to L5-S1 using musculoskeletal simulations. RESULTS: In 104 simulations, pre-surgical forces were equal to post-surgical. The levels L4-L5 and T12-L1, however, showed increased spinal forces compression forces with higher sagittal displacement. Improved restauration of sagittal balance was accompanied by lower spinal load. AP shear stress, interestingly decreased with sagittal imbalance. CONCLUSION: Imbalanced spines have a risk of increased compression forces at Th12-L1. L4-L5 always has increased spinal loads. These slides can be retrieved under Electronic Supplementary Material. KW - AnyBody Modeling System KW - Musculoskeletal analysis KW - Sagittal balance KW - Spinal fusion KW - Spine biomechanics KW - Biomechanische Analyse KW - Wirbelsäulenversteifung KW - Vergleichende Anatomie Y1 - 2018 U6 - https://doi.org/10.1007/s00586-018-5476-5 VL - 27 IS - 8 SP - 1905 EP - 1910 PB - Springer-Verlag ER - TY - CHAP A1 - Gross, Simon A1 - Verkerke, Gijsbertus Jacob A1 - Dendorfer, Sebastian T1 - Combined Experimental and Numerical Approach to Investigate Changes in Muscle Recruitment Pattern of the Back Muscles during Exhausting Exercise T2 - World Congress Biomechanics Dublin, 2018 N2 - In recent years, musculoskeletal computation has become a widely used tool to investigate joint and muscle forces within the human body. However, the issue of muscle fatigue is not considered adequately in most models and is a challenging task. One aspect that needs to be examined is the interaction of muscles during an exhausting task. Therefore, an experimental study was designed to analyze the changes of back muscle recruitment pattern during such exercises. In this study 38 subjects (27 male, 11 female, height = 177±8.5 cm, weight = 74.0±13.6 kg) participated. Each subject had to perform three static and three dynamic exhausting exercises where the back muscles were loaded with subject specific forces using a dynamometer adapter especially designed for the trunk muscles. To collect the muscle activity, twelve surface electromyography sensors were applied on the back, and four on the abdominal muscles. Muscle activity and fatigue were analyzed by calculating the maximum voluntary contraction normalized signal and the median frequency. At first the fatigue of m. erector spinae and m. multifidi was analyzed, since these muscles carry the main load during the exercises. Subsequently the activity of the m. trapezius, m. rectus abdominis and m. obliquus externus were investigated to determine recruitment patterns. To gain more detailed information of these patterns a numerical model was built using the AnyBody Modeling System™. Analyzing the measurements, we can observe an increasing muscle activity during isokinetic exercises while the force is constant. Since the activity in the simulation is defined as the current force output divided by the strength of the muscle, the strength parameter was scaled down based on the measured data, assuming a linear force – activity correlation, and using a numerical algorithm considering the influence of cross talk. The results show, that changes in recruitment pattern can be divided into three major subgroups. Prior to total exhaustion, some of the subjects show additional activation of muscles in the trapezius region, while other subjects show an additional activation of abdominal muscles, increasing the intra-abdominal pressure which supports the spine. In the third group an activation in both regions can be observed. The numerical simulations show an increasing activity of abdominal muscles as well as muscles in the upper back. Especially the m. latissimus dorsi shows a significantly higher activity. The results lead to the conclusion that prior to total exhaustion, additional muscles are recruited to support the main muscles. It was shown that abdominal muscles are activated to support back muscles by pressurizing the trunk cavity to delay total exhaustion as long as possible. In conclusion, the results show that changes in muscle recruitment pattern need to be considered when introducing muscle fatigue to musculoskeletal models. Y1 - 2018 ER -