Introduction-Extracellular matrix changes occur in many heart valve pathologies. For example, myxomatous mitral valves are reported to contain excess proteoglycans (PGs) and hyaluronan (HA). However, it is unknown which specific PGs are altered in myxomatous valves. Because PGs perform varied functions in connective tissues, this study was designed to identify and localize three matrixassociated PGs as well as HA and the HA receptor for endocytosis (HARE) within myxomatous and normal mitral valves.Methods-Human mitral posterior leaflets (control n=6−9, myxomatous n=14−21, mean age 61 for all groups) were histochemically stained for PG core proteins, HA, and HARE. Stain intensity was semi-quantitatively graded to determine differences in marker abundance betweennormal and myxomatous valves. The PGs were localized to different regions of the leaflet by correspondence to parallel Movat stained sections Results-The PGs decorin, biglycan and versican were more abundant in myxomatous valves than in normal controls (p<0.03). There was a gender effect on PG presence but no age related trends were observed. HA and HARE were distributed throughout all valves. There was no significant difference in HA between groups, but HARE expression was reduced in myxomatous valves compared to normal controls (p<0.002).Conclusion-Excess decorin, biglycan and versican may be associated with the remodeling of other matrix components in myxomatous mitral valves. Decreased expression of HARE in myxomatous valves suggests that HA metabolism could be altered in myxomatous mitral valve disease. These finding contribute towards elucidating the pathogenesis of myxomatous mitral valve disease and developing potential new therapies.

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Previous research in our lab suggested that heart valve tissues cultured without mechanical stimulation do not retain their in vivo microstructure, i.e., cell density decreased within the deep tissue layers and increased at the periphery. In this study, a splashing rotating bioreactor was designed to apply mechanical stimulation to a mitral valve leaflet segment. Porcine valve segments (n=9–10 per group) were cultured in the bioreactor for two weeks (dynamic culture); negative controls were cultured without mechanical stimulation (static culture), and baseline controls were fresh uncultured samples. Overall changes in cellularity and ECM structure were assessed by H&E and Movat pentachrome stains. Tissues were also immunostained for multiple extracellular matrix (ECM) components and turnover mediators. After two weeks of culture, proliferating cells were distributed throughout the tissue in segments cultured in the bioreactor, in contrast to segments cultured without mechanical stimulation. Most ECM components, especially collagen types I and III, better maintained normal expression patterns and magnitudes (as found in baseline controls) over two weeks of dynamic organ culture compared to static culture. Lack of mechanical stimulation changed several aspects of the tissue microstructure, including the cell distribution and ECM locations. In conclusion, mechanical stimulation by the bioreactor maintained tissue integrity, which will enable future in vitro investigation of mitral valve remodeling.

It is a delicate task to accurately assess the impact of solar particle events (SPEs) on future long‐duration human exploration missions. In the past, researchers have used several functional forms to fit satellite data for radiation exposure estimation. In this work we present a segmental power law interpolating algorithm to stream satellite data and get time series of proton spectra, which can be used to derive dosimetric quantities for any short period during which a single SPE or multiple SPEs occur. Directly using the corrected High Energy Proton and Alpha Detector fluxes of GOES, this method interpolates the intensity spectrum of a typical SPE to hundreds of MeV and extrapolates to the GeV level as long as sufficient particles are recorded in the high‐energy sensors. The high‐energy branch of the May 2012 SPE is consistent with the Band functional fitting, which is calibrated with ground level measurement. Modeling simulations indicate that the input spectrum of an SPE beyond 100 MeV is the major contributor for dose estimation behind the normal shielding thickness of spacecraft. Applying this method to the three SPEs that occurred in 2012 generates results consistent with two sets of in situ measurements, demonstrating that this approach could be a way to perform real‐time dose estimation. This work also indicates that the galactic cosmic ray dose rate is important for accurately modeling the temporal profile of radiation exposure during an SPE.