Dudleypetersson3278

Raman spectroscopy was used to evaluate spatial and temporal post-RTx changes to cortical bone composition in age-matched RTx and non-RTx groups. Results Significant early spatial differences in mineral/matrix and collagen crosslink ratios were found between endosteal and periosteal or mid-cortical bone at 2-wks post-RTx. Although spatial differences were transient, mineral/matrix ratios significantly decreased and collagen crosslink ratios significantly increased with post-RTx time throughout the entire tibial metaphyseal cortex. Conclusions Irradiation negatively impacts the composition of cortical bone in a spatially-dependent manner starting as early as 2-wks post-RTx. Long-term progressive post-RTx changes across all cortical bone sites may eventually contribute to the increased risk of post-RTx bone fragility fractures. © 2020 The Author(s).Even though the receptor activator of the nuclear factor-κB ligand (RANKL) and its receptor RANK have an exclusive role in osteoclastogenesis, the possibility of RANKL/RANK-independent osteoclastogenesis has been the subject of a long-standing debate in bone biology. In contrast, it has been reported that calvarial injection of TNF-ɑ elicits significant osteoclastogenesis in the absence of RANKL/RANK in NF-κB2- and RBP-J-deficient mice, suggesting that inflammatory challenges and secondary gene manipulation are the prerequisites for RANKL/RANK-deficient mice to develop osteoclasts in vivo. Here we report that, even in the absence of RANKL (Rankl -/- ), cherubism mice (Sh3bp2 KI/KI ) harboring the homozygous gain-of-function mutation in SH3-domain binding protein 2 (SH3BP2) develop tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts spontaneously. The Sh3bp2 KI/KI Rankl -/- mice exhibit an increase in tooth exposure and a decrease in bone volume/total volume compared to Sh3bp2 +/+ Rankl -/- mice. The multinucleated cells were stained positively for cathepsin K. Osteoclastic marker gene expression in bone and serum TRAP5b levels were elevated in Sh3bp2 KI/KI Rankl -/- mice. Elevation of the serum TNF-ɑ levels suggested that TNF-ɑ is a driver for the RANKL-independent osteoclast formation in Sh3bp2 KI/KI mice. Our results provide a novel mutant model that develops osteoclasts independent of RANKL and establish that the gain-of-function of SH3BP2 promotes osteoclastogenesis not only in the presence of RANKL but also in the absence of RANKL. © 2020 The Authors.Many mechanical properties of cortical bone are largely governed by the underlying microarchitecture; however, the influence of microarchitecture on the fatigue life of bone is poorly understood. Furthermore, imaging-based studies investigating intracortical microarchitecture may expose bone samples to large doses of radiation that may compromise fatigue resistance. The purpose of this pilot study was to 1) investigate the relationship between intracortical microarchitecture and the fatigue life of human bone in compression and 2) examine the effects of synchrotron irradiation on fatigue life measurements. Cortical samples were prepared from the femoral and tibial shafts of three cadaveric donors. A subset of samples was imaged using synchrotron X-ray microCT to quantify microarchitecture, including porosity, canal diameter, lacunar density, lacunar volume, and lacunar orientation. A second group of control samples was not imaged and used only for mechanical testing. Fatigue life was quantified by cyclically loading both groups in zero-compression until failure. Increased porosity and larger canal diameter were both logarithmically related to a shorter fatigue life, whereas lacunar density demonstrated a positive linear relationship with fatigue life (r2 = 45-73%, depending on measure). Irradiation from microCT scanning reduced fatigue life measurements by 91%, but relationships with microarchitecture measurements remained. Additional research is needed to support the findings of this pilot study and fully establish the relationship between intracortical microarchitecture and the compressive fatigue life of bone. © 2020 The Authors.Statistical learning, the ability to extract regularities from the environment over time, has become a topic of burgeoning interest. Its influence on behavior, spanning infancy to adulthood, has been demonstrated across a range of tasks, both those labeled as tests of statistical learning and those from other learning domains that predated statistical learning research or that are not typically considered in the context of that literature. Given this pervasive role in human cognition, statistical learning has the potential to reconcile seemingly distinct learning phenomena and may be an under-appreciated but important contributor to a wide range of human behaviors that are studied as unrelated processes, such as episodic memory and spatial navigation.Purpose To quantify the interobserver variability among the most frequently encountered parenchymal patterns in High Resolution CT (HRCT) and to compare the interobserver variability in the application of the 2011 and 2018 usual interstitial pneumonia (UIP) criteria according to the joint guidelines from international thoracic and respiratory societies. Material and methods Two observers independently evaluated 126 HRCT, with examples of most common parenchymal patterns, and noted the presence of each pattern. The readers also noted whether the findings met the 2011 criteria for UIP. In a second reading, the same readers noted whether the HRCT met the UIP criteria according to the 2018 UIP update. Results The kappa values for interobserver variability for the different patterns ranged from 0.28 (intralobular lines) to 0.85 (tree-in-bud nodules). The kappa value for UIP pattern was similar for 2011 and 2018 criteria, 0.58 and 0.69, respectively. Compared to the 2011 UIP criteria, there was no statistically significant difference in the number of HRCT classified as UIP using the 2018 criteria. Conclusions There is a substantial variation in interobserver agreement between the different parenchymal patterns, which suggests that some patterns a more easily identified than others. There is also a considerable reader variation in the assessment of UIP applying the 2011 UIP criteria as well as applying the 2018 UIP update. https://www.selleckchem.com/products/CP-690550.html © 2020 The Authors.