Cardiopulmonary dysfunction in the Osteogenesis imperfecta mouse model Aga2 and human patients are caused by bone-independent mechanisms.

Osteogenesis imperfecta (OI) is an inherited connective tissue disorder with skeletal dysplasia of varying severity, predominantly caused by mutations in the collagen I genes (COL1A1/COL1A2). Extraskeletal findings such as cardiac and pulmonary complications are generally considered to be significant secondary features. Aga2, a murine model for human OI, was systemically analyzed in the German Mouse Clinic by means of in vivo and in vitro examinations of the cardiopulmonary system, to identify novel mechanisms accounting for perinatal lethality. Pulmonary and, especially, cardiac fibroblast of perinatal lethal Aga2/+ animals display a strong down-regulation of Col1a1 transcripts in vivo and in vitro, resulting in a loss of extracellular matrix integrity. In addition, dysregulated gene expression of Nppa, different types of collagen and Agt in heart and lung tissue support a bone-independent vicious cycle of heart dysfunction, including hypertrophy, loss of myocardial matrix integrity, pulmonary hypertension, pneumonia and hypoxia leading to death in Aga2. These murine findings are corroborated by a pediatric OI cohort study, displaying significant progressive decline in pulmonary function and restrictive pulmonary disease independent of scoliosis. Most participants show mild cardiac valvular regurgitation, independent of pulmonary and skeletal findings. Data obtained from human OI patients and the mouse model Aga2 provide novel evidence for primary effects of type I collagen mutations on the heart and lung. The findings will have potential benefits of anticipatory clinical exams and early intervention in OI patients.

Southern women's response to a walking intervention.

The need to change the sedentary habits of many American adults is well recognized. Middle-aged women are an important target group for increased physical activity because of certain health risks such as osteoporosis. In the current study, 31 women between the ages of 30 and 60 from high- and low-income groups (high-income >$50,000; low-income <$50,000 per year) took part in a physical activity intervention. The goal was to increase walking activity to a minimum of 90 min per week. Each woman received 16 telephone calls over a 6-month period in which she was asked to reflect upon the benefits of walking, goal setting, restructuring plans, social support, exercise efficacy, relapse prevention, and maintenance. Content analysis revealed a number of themes emerging from intervention conversations. There were differences between races in walking location and walking partners. Furthermore, there were differences between income groups in beliefs about the benefits of walking and social support. Overall, the intervention appeared to provide a basis for women to develop a walking routine. The women were able to reflect upon their walking routine and attempts to begin a walking routine and to identify how each component of the intervention affected their individual daily routine.