Matrix GLA protein (MGP) is ubiquitously expressed with high accumulation in bone and cartilage, where it was found to associate with bone morphogenetic proteins (BMP) during protein purification. To test whether MGP affects BMP-induced differentiation, three sets of experiments were performed. First, pluripotent C3H10T1/2 cells transfected with human MPG (hMGP) or antisense to hMGP (AS-hMGP) were treated with BMP-2. In cells overexpressing hMGP, osteogenic and chondrogenic differentiation was inhibited indicating decreased BMP-2 activity. Conversely, in cells overexpressing AS-hMGP, BMP-2 activity was enhanced. Second, cells were prepared from homozygous and heterozygous MPG-deficient mice aortas. When treated with BMP-2, these cells underwent chondrogenic and osteogenic differentiation, respectively, whereas controls did not. Third, FLAG-tagged hMGP with the same biological effect as native hMGP inhibited BMP-induced differentiation, when exogenously added to culture media. Together, these results suggest that MGP modulates BMP activity. To test whether hMGP fragments would retain the effect of full-length hMGP, three subdomains were overexpressed in C3H10T1/2 cells. In cells expressing the mid-region, alone (amino acids (aa) 35-54) or in combination with the N terminus (aa 1-54) but not the C terminus (aa 35-84), osteogenic differentiation was enhanced and occurred even without added BMP-2. Thus, two subdomains had the opposite effect of full-length hMGP, possibly due to different expression levels or domain characteristics.Matrix GLA protein (MGP) 1 is a small ubiquitous matrix protein containing carboxyglutamic acid (GLA) (calculated mass of mature protein 10.4 kDa), initially isolated from bone and characterized by Price et al. (1). Results from other investigators suggest that MGP affects differentiation in developing cartilage and bone. Luo et al. (2) observed that MGP is expressed in early and late stages of chondrogenic differentiation but not in the intermediate stage. Yagami et al. (3) found that MGP had an effect on mineralization in chondrocytes that was dependent on cell stage; it affected mineralization in hypertrophic chondrocytes but not in proliferative chondrocytes. They also found that overexpression of MGP in developing limb buds delayed chondrocyte maturation and blocked endochondral ossification. In MGP null (MGPϪ/Ϫ) mice (4), the epiphyseal growth plates of bones showed inappropriate calcification in the layer of proliferating chondrocytes that failed to differentiate into hypertrophic chondrocytes. In addition, the mice unexpectedly developed severe vascular calcification, resulting from a replacement of the aortic medial layer by chondrocytelike cells, producing a typical cartilage matrix that progressively calcified.When Urist and colleagues (5) first discovered bone morphogenetic protein (BMP), they observed a tight association with MGP in vitro during protein purification requiring strong denaturants to break. Although complex formation was not shown in vivo or in situ, it was sug...
A multidisciplinary team led by nursing leadership and physicians developed a plan to meet increasing demand and improve the patient experience in the ED without expanding the department's current resources. The approach included Lean tools and engaged frontline staff and physicians. Applying Lean management principles resulted in quicker service, improved patient satisfaction, increased capacity, and reduced resource utilization. Incorporating continuous daily management is necessary for sustainment of continuous improvement activities.
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Background: For 20 years, telemedicine has been waiting in the wings for its time in the spotlight. The Coronavirus Disease 2019 (COVID-19) pandemic, with its emphasis on personal protective equipment (PPE) and reducing high-risk contacts, was the catalyst needed to bring telemedicine into mainstream consciousness and acceptance. Objectives: We first review some of the key factors that precipitated this abrupt alteration of the perception of telemedicine. We then detail the creation of a department-wide telemedicine network using off-the-shelf consumer products. Our goal was to very rapidly install a system that was familiar to end-users for the purpose of reducing high-risk contacts and conserving PPE. Sourcing from the consumer realm proved to be advantageous over enterprise-level equipment when these goals were desired. Discussion: After a rollout of 1.5 weeks from zero to fully operational, we showed an immediate decrease in highrisk contacts and PPE use. All 80 rooms plus all triage areas in our department were outfitted with Apple iPads running Zoom. User adoption was high and telemedicine use increased from $17 to $90 instances a day, a 429% increase. We saw a decrease in high-risk contacts of about 75%, with a concomitant cost savings in PPE. Conclusions: We propose that the use of consumer products sourced from local vendors is a viable solution for telemedicine systems focusing on speed, reducing costs, and ease of deployment. Future work will focus on studying its performance characteristics vs. other systems in an evolving landscape.
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