Significant mitral valve regurgitation creates progressive adverse remodeling of the left ventricle (LV). Replacement of the failing valve with a prosthesis generally improves patient outcomes but leaves the patient with non-physiological intracardiac flow patterns that might contribute to their future risk of thrombus formation and embolism. It has been suggested that the angular orientation of the implanted valve might modify the postoperative distortion of the intraventricular flow field. In this study, we investigated the effect of prosthetic valve orientation on LV flow patterns by using heart geometry from a patient with LV dysfunction and a competent native mitral valve to calculate intracardiac flow fields with computational fluid dynamics (CFD). Results were validated using in vivo 4D Flow MRI. The computed flow fields were compared to calculations following virtual implantation of a mechanical heart valve oriented in four different angles to assess the effect of leaflet position. Flow patterns were visualized in long- and short-axes and quantified with flow component analysis. In comparison to a native valve, valve implantation increased the proportion of the mitral inflow remaining in the basal region and further increased the residual volume in the apical area. Only slight changes due to valve orientation were observed. Using our numerical framework, we demonstrated quantitative changes in left ventricular blood flow due to prosthetic mitral replacement. This framework may be used to improve design of prosthetic heart valves and implantation procedures to minimize the potential for apical flow stasis, and potentially assist personalized treatment planning.Despite the wide-spread use of musculoskeletal simulations and its use in estimating spinal loads, much is not known about how to best collect experimental data for modelling purposes. The primary purposes in this study were to determine the effects of tracking of running motion capture data to a model (1) with and without coupling of lumbar spine segments, and (2) with varying combinations of spinal markers. Running trials were collected from 7 participants, with each at three different speeds. The motion data was fit to the Full-Body Lumbar Spine Model (FBLS) with coupling of the lumbar spine enabled (CS) and disabled and therefore rigid (RS) in OpenSim through the Inverse Kinematics tool (IK).  https://www.selleckchem.com/products/ro-3306.html  Different combinations of markers were chosen as tracking inputs for IK to represent experimental data collection with different marker sets. Root-mean-square (RMS) marker errors of all 13 markers along the spine for each gait cycle were calculated. The CS model resulted in 23.7% lower errors than the RS model (p less then 0.001). The marker subset analysis showed that increasing the number of markers in the experimental data collection decreases the error, with the four marker tracking subsets with the highest number of markers tracked having the lowest errors. The location of the marker and timing in the gait cycle did not affect marker error. When spinal mechanics are of interest, the inclusion of a coupled lumbar spine in the model and a larger spinal marker set help better track experimental kinematics when fitting to a model.The pelvis functions to transmit upper body loads to the lower limbs and is critical in human locomotion. Semi-automated, finite element (FE) morphing techniques eliminate the need for segmentation and have shown to accelerate the generation of multiple specimen-specific pelvic FE models to enable the study of pelvic mechanical behaviour. The purpose of this research was to produce simulated human pelvic FE models representing android, gynecoid, anthropoid and platypelloid morphologies and to isolate differences in strain patterns due to anatomic shape under physiologic loading. Using five initially generated specimen-specific FE models, each specimen-specific FE model was reconfigured into three different morphologies using FE mesh morphing techniques. Significantly different strains were found comparing the gynecoid (classical female pelvis') to the android ('true male pelvis') models (p = 0.040), with strains twice as high in the superior pubic rami. No significant differences were seen in comparing overall strains between the other pelvic shapes (p = 0.61-0.126). The highest strain regions in all models were found in the supra-acetabular regions, with high strains also found in the regions of the superior pubic rami, the greater sciatic notch and sacral regions about the L5 vertebrae. Quantifying the contributions of shape to strain in the pelvis may increase the understanding of sex and patient-specific differences in fracture risk and motivate the consideration of treatment strategies that account for anatomic pelvic differences.Hair cells can be regenerated after damage by transdifferentiation in which a supporting cell directly differentiates into a hair cell without mitosis. However, such regeneration is at the cost of exhausting the support cells in the mammalian mature cochlea. Thus, more effective methods should be found to promote mitotic regeneration but partially preserve support cells after damage. To address the issue, we first injured hair cells in the chick basilar papillae (BP) by treatment with streptomycin in vitro. We then compared the mitotic regeneration on the neural side in the middle part of BP after treatment with a pharmacological inhibitor or agonist of the Notch (DAPT), Wnt (LiCl), Bmp (Noggin) or Fgf (SU5402) signaling pathway, with that after treatment with combinations of two or three inhibitors or agonist of these pathways. Our results indicate that treatments with a single inhibitor or agonist of the Notch, Wnt, Bmp or Fgf signaling pathway could significantly increase mitotic regeneration as well as direct transdifferentiation. The results also show that hair cells (Myosin 7a+), support cells (Sox2+) and mitotically regenerated hair cells (Myosin 7a+/Sox2+/BrdU+) increased significantly on the neural side in the middle part of BP after two or three combinations of the inhibition of Notch, Bmp or Fgf signaling pathway or the activation of Wnt signaling pathway, besides the reported coregulatory effects of Notch and Wnt signaling. The study of the effects of systematic combinations of pathway modulators provided more insight into hair cell regeneration from mitosis.