Effects of Optimization Technique on Simulated Muscle Activations and Forces.

Two optimization techniques, static optimization (SO) and computed muscle control (CMC), are often used in OpenSim to estimate the muscle activations and forces responsible for movement. Although differences between SO and CMC muscle function have been reported, the accuracy of each technique and the combined effect of optimization and model choice on simulated muscle function is unclear. The purpose of this study was to quantitatively compare the SO and CMC estimates of muscle activations and forces during gait with the experimental data in the Gait2392 and Full Body Running models. In OpenSim (version 3.1), muscle function during gait was estimated using SO and CMC in 6 subjects in each model and validated against experimental muscle activations and joint torques. Experimental and simulated activation agreement was sensitive to optimization technique for the soleus and tibialis anterior. Knee extension torque error was greater with CMC than SO. Muscle forces, activations, and co-contraction indices tended to be higher with CMC and more sensitive to model choice. CMC's inclusion of passive muscle forces, muscle activation-contraction dynamics, and a proportional-derivative controller to track kinematics contributes to these differences. Model and optimization technique choices should be validated using experimental activations collected simultaneously with the data used to generate the simulation.

Medially-stabilized total knee arthroplasty does not alter knee laxity and balance in cadaveric knees.

Instability after total knee arthroplasty (TKA) can lead to suboptimal outcomes and revision surgery. Medially-stabilized implants aim to more closely replicate normal knee motion than other implants following TKA, but no study has investigated knee laxity (motion under applied loads) and balance (i.e., difference in varus/valgus motion under load) following medially-stabilized TKA. The primary purposes of this study were to investigate how medially-stabilized implants change knee laxity in non-arthritic, cadaveric knees, and if it produces a balanced knee after TKA. Force-displacement data were collected on 18 non-arthritic cadaveric knees before and after arthroplasty using medially-stabilized implants. Varus-valgus and anterior-posterior laxity and varus-valgus balance were compared between native and medially-stabilized knees at 0°, 20°, 60°, and 90° under three different loading conditions. Varus-valgus and anterior-posterior laxities were not different between native and medially-stabilized knees under most testing conditions (p ≥ 0.068), but differences of approximately 2° less varus-valgus laxity at 20° of flexion and 4 mm more anterior-posterior laxity at 90° were present from native laxities (p < 0.017) Medially-stabilized implant balance had ≤1.5° varus bias at all flexion angles. Future studies should confirm if the consistent laxity afforded by the medially-stabilized implant is associated with better and more predictable postoperative outcomes. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:335-349, 2019.

Expression and prognostic assessment of dipeptidyl peptidase IV and related enzymes in B-cell chronic lymphocytic leukemia.

Recent observations of the deregulated expression of several dipeptidyl peptidase (DP) IV-like enzymes in human cancers have led to presumptions of their pathogenic role in cancer. To further explore this concept we have characterized the expression of all DPIV-like enzymes in chronic lymphocytic leukemia (CLL). We have demonstrated the constitutive expression of DPIV, DP8, DP9, DPII and PEP mRNA and DPIV, DP8 and DP9 protein in CLL. FAP mRNA was not detected in CLL or normal B-lymphocytes. This correlated with an absence of FAP protein on the cell surface. This study also shows that DP8 mRNA expression is significantly upregulated in CLL compared to normal tonsil B-lymphocytes (p < 0.05) which may suggest biological importance in this disease. DP expression could not be correlated with any molecular or clinical prognostic markers for CLL in this cohort including IgVH mutational status, CD38, ZAP-70 or CD49d expression (n = 58). However, the constitutive expression of the DPIV-like enzymes in CLL and their emergence as potent immune regulators makes them candidate therapeutic targets in this disease.