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Formation of advanced glycation end products (AGEs) in extracellular matrix (ECM) is implicated in the development of chronic diabetic complications. However, the involvement of AGEs in diabetic bone disease has not been well established. We have examined whether AGEs are increased in the bone collagen of streptozotocin-induced diabetic rats in vivo and whether glycation of type I collagen affects the functions of osteoblastic cells in vitro. During 12 weeks of observation, AGEs in collagen extracted from the tibiae of diabetic rats increased in a time-dependent manner and were significantly higher than controls at every time point. In vitro, the incubation of collagen with glucose-6-phosphate resulted in a time-dependent increase of AGEs. When osteoblastic cells isolated from fetal rat calvaria were cultured on AGE-modified type I collagen, it dose-dependently inhibited phenotypic expressions of osteoblasts. Among osteoblastic parameters, nodule formation was the most sensitive, being inhibited by approximately 70% by the glycation of collagen for only 1 week. Alkaline phosphatase activity and osteocalcin secretion were inhibited by 20-30% and 15-70%, respectively, by the glycation of collagen for 1-5 weeks. These results indicate that AGE-modified collagen affects osteoblastic cell differentiation and function in vitro and suggest that similar changes occurring in vivo may contribute to diabetic osteopenia.

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Flow experience is a subjective state experienced during holistic involvement in a certain activity, which has been reported to function as a factor promoting motivation, skill development, and better performance in the activity. To verify the positive effects of flow and develop a method to utilize it, the establishment of a reliable measurement of the flow state is essential. The present study utilized an electroencephalogram (EEG) during an experimentally evoked flow state and examined the possibility of objective measurement of immediate flow. A total of 16 participants (10 males, 6 females) participated in the experiment that employed a mental arithmetic task developed in a previous study. Post-trial self-report of the flow state and EEG during task execution were measured and compared among three conditions (Boredom, Flow, and Overload) that had different levels of task difficulty. Furthermore, the correlations between subjective flow items and EEG activity were examined. As expected, the ratings on the subjective evaluation items representing the flow state were the highest in the Flow condition. Regarding the EEG data, theta activities in the frontal areas were higher in the Flow and the Overload conditions than in the Boredom condition, and alpha activity in the frontal areas and the right central area gradually increased depending on the task difficulty. These EEG activities correlated with self-reported flow experience, especially items related to the concentration on the task and task difficulty. From the results, the flow state was characterized by increased theta activities in the frontal areas and moderate alpha activities in the frontal and central areas. The former may be related to a high level of cognitive control and immersion in task, and the latter suggests that the load on the working memory was not excessive. The findings of this study suggest the possibility of distinguishing the flow state from other states using multiple EEG activities and indicate the need for other physiological indicators corresponding to the other aspects of flow experience.

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