Colon epithelial cell-specific Bmal1 deletion impairs bone formation in mice.

The circadian clock system regulates multiple metabolic processes, including bone metabolism. Previous studies have demonstrated that both central and peripheral circadian signaling regulate skeletal growth and homeostasis in mice. Disruption in central circadian rhythms has been associated with a decline in bone mineral density in humans and the global and osteoblast-specific disruption of clock genes in bone tissue leads to lower bone mass in mice. Gut physiology is highly sensitive to circadian disruption. Since the gut is also known to affect bone remodeling, we sought to test the hypothesis that circadian signaling disruption in colon epithelial cells affects bone. We therefore assessed structural, functional, and cellular properties of bone in 8 week old Ts4-Cre and Ts4-Cre;Bmal1fl/fl (cBmalKO) mice, where the clock gene Bmal1 is deleted in colon epithelial cells. Axial and appendicular trabecular bone volume was significantly lower in cBmalKO compared to Ts4-Cre 8-week old mice in a sex-dependent fashion, with male but not female mice showing the phenotype. Similarly, the whole bone mechanical properties were deteriorated in cBmalKO male mice. The tissue level mechanisms involved suppressed bone formation with normal resorption, as evidenced by serum markers and dynamic histomorphometry. Our studies demonstrate that colon epithelial cell-specific deletion of Bmal1 leads to failure to acquire trabecular and cortical bone in male mice.

The American Association for the Surgery of Trauma (AAST) Liver Injury Grade Does Not Equally Predict Interventions in Blunt and Penetrating Trauma.

INTRODUCTION: The AAST liver injury grade has a validated association with mortality and need for operation. AAST liver injury grade is the same regardless of the mechanism of trauma. METHODS: A 5-year retrospective review of all liver injuries at an urban, level-one trauma center was performed. RESULTS: Totally, 315 patients were included (29% blunt, 71% penetrating). In blunt trauma, AAST grade was associated with need for laparotomy (0%, 7%, 5%, 33%, 29%, Grade 1-5, p = 0.01), angiography (0%, 7%, 25%, 40%, 57%, p < 0.001), embolization (0%, 7%, 15%, 33%, 43%, p = 0.01), and percutaneous drainage procedures (13% use in Grade 4, otherwise 0%, p = 0.04), but not ERCP (0% for all grades). In penetrating trauma, AAST grade was associated with need for angiography (7%, 4%, 15%, 24%, 30%, p < 0.01) and percutaneous drainage (7%, 2%, 14%, 18%, 26%, p = 0.03) and had a marginal association with embolization (0%, 4%, 11%, 13%, 22%, p = 0.06). Laparotomy, ERCP, sphincterotomy, and stenting rates increased with AAST grade, but this was not statistically significant. CONCLUSION: AAST grade is associated with the need for surgical hemostasis, angioembolization, and percutaneous drainage in both penetrating and blunt trauma. Operative, endoscopic, and percutaneous procedures are utilized more in penetrating trauma. Angioembolization was used more in blunt trauma. Mechanism should be considered when using AAST grade to guide management of liver injuries.