Histone Deacetylase 3 Depletion in Osteo/Chondroprogenitor Cells Decreases Bone Density and Increases Marrow Fat

Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO) mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health

Unraveling the Shift to the Entrepreneurial Economy

A recent literature has emerged providing compelling evidence that a major shift in the organization of the developed economies has been taking place: away from what has been characterized as the managed economy towards the entrepreneurial economy. In particular, the empirical evidence provides consistent support that (1) the role of entrepreneurship has significantly increased, and (2) a positive relationship exists between entrepreneurial activity and economic performance. However, the factors underlying this observed shift have not been identified in a systematic manner. The purpose of this paper is to suggest some of the factors leading to this shift and implications for public policy. In particular, we find that a fundamental catalyst underlying the shift from the managed to the entrepreneurial economy involved the role of technological change. However, we also find that it was not just technological change but rather involved a number of supporting factors, ranging from the demise of the communist system, increased globalization, new competition for multinational firms and higher levels of prosperity. Recognition of the causes of the shift from the managed to the entrepreneurial economy suggests a rethinking of the public policy approach. Rather than the focus of directly and exclusively on promoting startups and SMEs, it may be that the current approach to entrepreneurship policy is misguided. The priority should not be on entrepreneurship policy but rather a more pervasive and encompassing approach, policy consistent with an entrepreneurial economy

Impact of preoperative physical activity and depressive symptoms on post-cardiac surgical outcomes.

OBJECTIVE:To determine the independent and combined impact of preoperative physical activity and depressive symptoms with hospital length of stay (HLOS), and postoperative re-hospitalization and mortality in cardiac surgery patients. METHODS:A cohort study including 405 elective and in-house urgent cardiac surgery patients were analyzed preoperatively. Physical activity was assessed with the International Physical Activity Questionnaire to categorize patients as active and inactive. The Patient Health Questionnaire-9 was used to evaluate preoperative depressive symptoms and categorize patients as depressed and not depressed. Patients were separated into four groups: 1) Not depressed/active (n = 209), 2) Depressed/active (n = 48), 3) Not depressed/inactive (n = 101), and 4) Depressed/inactive (n = 47). Administrative data captured re-hospitalization and mortality data, and were combined into a composite endpoint. Models adjusted for demographics, comorbidities, and cardiac surgery type. Multiple imputation was used to impute missing values. RESULTS:Preoperative physical activity behavior and depression were not associated with HLOS examined in isolation or when analyzed by the physical activity/depressive symptom groups. Physical inactivity (HR: 1.60, 95% CI 1.05 to 2.42; p = 0.03), but not depressive symptoms, was independently associated with the composite outcome. Freedom from the composite outcome were 76.1%, 87.5%, 68.0%, and 61.7% in the Not depressed/active, Depressed/active, Not depressed/inactive, and Depressed/inactive groups, respectively (P = 0.02). The Active/Depressed group had a lower risk of the composite outcome (HR: 0.35 95% CI 0.14 to 0.89; p = 0.03) compared to the other physical activity/depression groups. CONCLUSION:Preoperative physical activity appears to be more important than depressive symptoms on short-term postoperative re-hospitalization and mortality