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“Obesity is a growing issue of the modern world, and its negative impact on bones in obese male patients has been recently reported. The Wnt/beta-catenin pathway has an established role in the regulation of body fat content and bone density. We investigated the effects of indirubin-3′-oxime (I3O), the GSK3 beta inhibitor that activates Wnt/beta-catenin AR-13324 chemical structure signaling, on trabecular bone in high-fat diet (HFD)-induced obese male mice. I3O reverses the downregulating effect of fatty acid (FA) on Wnt/beta-catenin signaling and enhances the osteogenic commitment

of the bone marrow-derived stromal cell line ST2. FA induces the adipogenic differentiation of bone marrow stromal cells in vitro. In a male mouse model of HFD-induced obesity, trabecular bone loss was observed in the femora, SB273005 Cytoskeletal Signaling inhibitor with a gross increase in abdominal fat; however, the HFD effects were rescued with the activation of Wnt/beta-catenin signaling by I3O treatment. I3O administration also reversed the increase in the number of HFD-induced adipocytes in the femur bone marrow in trabecular bone. Overall, our results indicate that I3O could be a potential therapeutic agent for obese

male patients through downregulation of abdominal fat and net increment in trabecular bone density. (C) 2014 Elsevier Inc. All rights reserved.”
“Background: We examined the impact of data source and exposure measurement error for ambient NO2 on risk estimates derived from a case-crossover study of emergency room visits for asthma in Windsor, Canada between 2002 and 2009. Methods: Paired LY2090314 manufacturer personal and fixed-site NO2 data were available from an independent population (47 children and 48 adults) in Windsor between 2005 and 2006. We used linear regression to estimate the relationship and measurement error variance induced between fixed site and personal measurements of NO2, and through a series of simulations, evaluated the potential for a Bayesian model to adjust for this change in scale and measurement error. Finally, we re-analyzed data from the previous case-crossover study adjusting for the estimated

change in slope and measurement error. Results: Correlations between paired NO2 measurements were weak (R-2 smaller than = 0.08) and slopes were far from unity (0.0029 smaller than = beta smaller than = 0.30). Adjusting the previous case-crossover analysis suggested a much stronger association between personal NO2 (per 1 ppb) (Odds Ratio (OR)=1.276, 95% Credible Interval (CrI): 1.034, 1.569) and emergency room visits for asthma among children relative to the fixed-site estimate (OR=1.024, 95% CrI 1.004-1.045). Conclusions: Our findings suggest that risk estimates based on fixed-site NO2 concentrations may differ substantially from estimates based on personal exposures if the change in scale and/or measurement error is large.