The molecular mechanisms of chronic pain are poorly understood and effective mechanism-based treatments are lacking. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected chronic mechanical and thermal hypersensitivity due to sustained elevated circulating adenosine. Extending from Ada−/− mice, we further discovered that prolonged elevated adenosine contributed to chronic pain behaviors in two additional independent animal models:1) sickle cell disease mice, a model of severe pain with limited treatment, and 2) complete Freund’s adjuvant paw-injected mice, a well-accepted inflammatory model of chronic pain. Mechanistically, we revealed that activation of adenosine A2B receptors on myeloid cells caused nociceptor hyperexcitability and promoted chronic pain via soluble IL-6 receptor trans-signaling, our findings determined that prolonged accumulated circulating adenosine contributes to chronic pain by promoting immune-neuronal interaction and revealed multiple therapeutic targets.
Using (18)F-fluorodopa PET and a constant 0.0062 influx rate in the putamen, dementia with Lewy bodies (n = 7) was distinguished from AD (n = 10) with a sensitivity of 86% and a specificity of 100%. A constant 0.0071 influx rate in the caudate yielded a sensitivity of 71% and a specificity of 100% for distinction of the two disorders. Despite a limited sample size, these findings suggest that assessing nigrostriatal dopaminergic function with (18)F-fluorodopa PET may be a useful diagnostic aid in cases of dementia with Lewy bodies while patients are alive.
For a company to survive in the long run, it is necessary to attract enough customers to generate profitability. Since the high uncertainty in organizations requires a more rapid response to customers’ needs, agility is a critical success factor for today’s manufacturing enterprise. To be competitive, enterprises must integrate their supply chains more effectively and forge close memberships with customers and suppliers more quickly. Therefore, the current study attempts to understand how supply chain agility has evolved. We have used a systematic literature review approach to examine the current state of the art and identify potential research gaps. It has indicated how companies can form and preserve competitive advantages in turbulent environments between manufacturers and consumers. From the outcomes, it can be observed that the developed supply chain agility has positive impacts on the sales of companies, velocity to market, profitability, market share and consumers’ satisfaction. Also, the investigations showed that the supply chain agility management needs persistent planning. Allotment of the resources to the agility aspects’ improvement might help companies increase the influence of such investments. Our investigation highlights the tactics for better readiness to attain supply chain agility that is the central part of electronic firms' competency in an emerging market.
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