Clinical implementation of quantitative computed tomography-based finite element analysis (QCT/FEA) of proximal femur stiffness and strength to assess the likelihood of proximal femur (hip) fractures requires a unified modeling procedure, consistency in predicting bone mechanical properties, and validation with realistic test data that represent typical hip fractures, specifically, a sideways fall on the hip. We, therefore, used two sets (n = 9, each) of cadaveric femora with bone densities varying from normal to osteoporotic to build, refine, and validate a new class of QCT/FEA models for hip fracture under loading conditions that simulate a sideways fall on the hip. Convergence requirements of finite element models of the first set of femora led to the creation of a new meshing strategy and a robust process to model proximal femur geometry and material properties from QCT images. We used a second set of femora to cross-validate the model parameters derived from the first set. Refined models were validated experimentally by fracturing femora using specially designed fixtures, load cells, and high speed video capture. CT image reconstructions of fractured femora were created to classify the fractures. The predicted stiffness (cross-validation R2 = 0.87), fracture load (cross-validation R2 = 0.85), and fracture patterns (83% agreement) correlated well with experimental data.

Despite an excellent initial treatment response, relapses are common, even in type 2, and almost half of the patients require maintenance therapy. Pancreatic insufficiency is highly prevalent, which calls for active screening. Pancreatic cancer was not observed, and quality of life and survival are not impaired.

Quantitative computed tomography based finite element analysis of the femur is currently being investigated as a method for non-invasive stiffness and strength predictions of the proximal femur. The specific objective of this study was to determine better conversion relationships from QCT-derived bone density to elastic modulus, in order to achieve accurate predictions of the overall femoral stiffness in a fall-on-the-hip loading configuration. Twenty-two femurs were scanned, segmented and meshed for finite element analysis. The elastic moduli of the elements were assigned according to the average density in the element. The femurs were then tested to fracture and force-displacement data was collected to calculate femoral stiffness. Using a training set of nine femurs, finite element analyses were performed and the parameters of the density-elastic modulus relationship were iteratively adjusted to obtain optimal stiffness predictions in a least-squares sense. The results were then validated on the remaining 13 femurs. Our novel procedure resulted in parameter identification of both power and sigmoid functions for density-elastic modulus conversion for this specific loading scenario. Our in situ estimated power law achieved improved predictions compared to published power laws, and the sigmoid function yielded even smaller prediction errors. In the future, these results will be used to further improve the femoral strength predictions of our finite element models.

In contrast to the lung and the myocardium, the liver is a relatively homogeneous organ with fewer anatomic constraints on vascular branching. Hence, we hypothesize that the hepatic vasculature could more closely follow optimization of branching geometry than is the case in other organs. The geometrical and fractal properties of the rat hepatic portal vein tree were investigated, with the aid of three-dimensional micro-computed tomography data. Frequency distributions of vessel radii were obtained at three different voxel resolutions and fitted to a theoretical model of dichotomous branching. The model predicted an average junction exponent of 3.09. Hemodynamic model calculations showed that with generation, relative shear stress decreases. Branching angles were found to oscillate between those predicted by two optimality principles of minimum power loss and volume, and of minimum shear stress and surface. The liver shows a variation in branching morphology similar to that of other organs. Therefore, we conclude that anatomic constraints do not have a major perturbing impact.

The main objective of the present study was to determine alterations of calcium handling in the diabetic rat heart during the transition from adaptive to maladaptive phase of cardiomyopathy. By inhibiting the nuclear enzyme poly(ADP-ribose) polymerase (PARP), we also investigated the possible role of this enzyme in the sequence of pathological events. Six weeks after induction of type I diabetes by injection of streptozotocin in rats, the hearts were perfused according to Langendorff. Intracellular-free calcium (Ca 2+ i) levels were measured by surface fluorometry using Indo-1 AM. Cyclic changes in Ca 2+ i concentrations and hemodynamic parameters were measured simultaneously. The hearts were challenged by infusion of isoproterenol. Six weeks of diabetes resulted in reduced inotropy and lusitropy. The diabetic hearts (DM) expressed a significantly elevated end-diastolic Ca 2+ i level (control, 111±20 vs DM, 221±35 nM). The maximal transport capacity of SERCA2a and conductance of RyR2 were reduced. These changes were not accompanied by major alterations in the tissue content of SERCA2a, RyR2, phospholamban and Na + /Ca 2+ exchanger. In response to ß-adrenergic activation, SERCA2a transport capacity and RyR2 conductance were stunted in the DM hearts. Inhibition of PARP induced minor changes in the mechanical function and calcium handling of the DM hearts. In conclusion, the observed changes in contractility and in Ca 2+ i handling are most likely attributable to functional disturbances of SERCA2a and RyR2 in this transitional phase of diabetes. At this stage of diabetes, PARP does not appear to play a significant pathogenetic role in the alterations in contractile function and calcium handling.