Background The gait modification strategies Trunk Lean and Medial Thrust have been shown to reduce the external knee adduction moment (EKAM) in patients with knee osteoarthritis which could contribute to reduced progression of the disease. Which strategy is most optimal differs between individuals, but the underlying mechanism that causes this remains unknown. Research question Which gait parameters determine the optimal gait modification strategy for individual patients with knee osteoarthritis? Methods Forty-seven participants with symptomatic medial knee osteoarthritis underwent 3-dimensional motion analysis during comfortable gait and with two gait modification strategies: Medial Thrust and Trunk Lean. Kinematic and kinetic variables were calculated. Participants were then categorized into one of the two subgroups, based on the modification strategy that reduced the EKAM the most for them. Multiple logistic regression analysis with backward elimination was used to investigate the predictive nature of dynamic parameters obtained during comfortable walking on the optimal modification gait strategy. Results For 68.1 % of the participants, Trunk Lean was the optimal strategy in reducing the EKAM. Baseline characteristics, kinematics and kinetics did not differ significantly between subgroups during comfortable walking. Changes to frontal trunk and tibia angles correlated significantly with EKAM reduction during the Trunk Lean and Medial Thrust strategies, respectively. Regression analysis showed that MT is likely optimal when the frontal tibia angle range of motion and peak knee flexion angle in early stance during comfortable walking are high (R2Nagelkerke = 0.12). Significance Our regression model based solely on kinematic parameters from comfortable walking contained characteristics of the frontal tibia angle and knee flexion angle. As the model explains only 12.3 % of variance, clinical application does not seem feasible. Direct assessment of kinetics seems to be the most optimal strategy for selecting the most optimal gait modification strategy for individual patients with knee osteoarthritis.
MULTIFILE
Development of novel testing strategies to detect adverse human health effects is of interest to replace in vivo-based drug and chemical safety testing. The aim of the present study was to investigate whether physiologically based kinetic (PBK) modeling-facilitated conversion of in vitro toxicity data is an adequate approach to predict in vivo cardiotoxicity in humans. To enable evaluation of predictions made, methadone was selected as the model compound, being a compound for which data on both kinetics and cardiotoxicity in humans are available. A PBK model for methadone in humans was developed and evaluated against available kinetic data presenting an adequate match. Use of the developed PBK model to convert concentration–response curves for the effect of methadone on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in the so-called multi electrode array (MEA) assay resulted in predictions for in vivo dose–response curves for methadone-induced cardiotoxicity that matched the available in vivo data. The results also revealed differences in protein plasma binding of methadone to be a potential factor underlying variation between individuals with respect to sensitivity towards the cardiotoxic effects of methadone. The present study provides a proof-of-principle of using PBK modeling-based reverse dosimetry of in vitro data for the prediction of cardiotoxicity in humans, providing a novel testing strategy in cardiac safety studies.
MULTIFILE
Recycling of plastics plays an important role to reach a climate neutral industry. To come to a sustainable circular use of materials, it is important that recycled plastics can be used for comparable (or ugraded) applications as their original use. QuinLyte innovated a material that can reach this goal. SmartAgain® is a material that is obtained by recycling of high-barrier multilayer films and which maintains its properties after mechanical recycling. It opens the door for many applications, of which the production of a scoliosis brace is a typical example from the medical field. Scoliosis is a sideways curvature of the spine and wearing an orthopedic brace is the common non-invasive treatment to reduce the likelihood of spinal fusion surgery later. The traditional way to make such brace is inaccurate, messy, time- and money-consuming. Because of its nearly unlimited design freedom, 3D FDM-printing is regarded as the ultimate sustainable technique for producing such brace. From a materials point of view, SmartAgain® has the good fit with the mechanical property requirements of scoliosis braces. However, its fast crystallization rate often plays against the FDM-printing process, for example can cause poor layer-layer adhesion. Only when this problem is solved, a reliable brace which is strong, tough, and light weight could be printed via FDM-printing. Zuyd University of Applied Science has, in close collaboration with Maastricht University, built thorough knowledge on tuning crystallization kinetics with the temperature development during printing, resulting in printed products with improved layer-layer adhesion. Because of this knowledge and experience on developing materials for 3D printing, QuinLyte contacted Zuyd to develop a strategy for printing a wearable scoliosis brace of SmartAgain®. In the future a range of other tailor-made products can be envisioned. Thus, the project is in line with the GoChem-themes: raw materials from recycling, 3D printing and upcycling.
