Double homeobox gene, Duxbl, promotes myoblast proliferation and abolishes myoblast differentiation by blocking MyoD transactivation.

Homeobox genes encode transcription factors that regulate embryonic development programs including organogenesis, axis formation and limb development. Previously, we identified and cloned a mouse double homeobox gene, Duxbl, whose homeodomain exhibits the highest identity (67 %) to human DUX4, a candidate gene of facioscapulohumeral muscular dystrophy (FSHD). Duxbl proteins have been shown to be expressed in elongated myocytes and myotubes of trunk and limb muscles during embryogenesis. In this study, we found that Duxbl maintained low expression levels in various adult muscles. Duxbl proteins were induced to express in activated satellite cells and colocalized with MyoG, a myogenic differentiating marker. Furthermore, Duxbl proteins were not detected in quiescent satellite cells but detected in regenerated myocytes and colocalized with MyoD and MyoG following cardiotoxin-induced muscle injury. Ectopic Duxbl overexpressions in C2C12 myoblast cells promoted cell proliferation through mainly enhancing cyclin D1 and hyper-phosphorylated retinoblastoma protein but reducing p21 expression. However, Duxbl overexpression in C2C12 cells inhibited myogenic differentiation by decreasing MyoD downstream gene expressions, including M-cadherin, MyoG, p21 and cyclin D3 but not MyoD itself. Duxbl overexpressions also promoted cell proliferation but blocked MyoD-induced myogenic conversion in multipotent mesenchymal C3H10T1/2 cells. In addition, results of a luciferase reporter assay suggest that Duxbl negatively regulated MyoG promoter activity through the proximal two E boxes. In conclusion, these results indicate that Duxbl may play a crucial role in myogenesis and postnatal muscle regeneration by activating and proliferating satellite and myoblast cells.

[The effect of bundle care on central line associated bloodstream infection in a medical intensive care unit].

BACKGROUND & PROBLEMS: While the central line catheter is a common device used in intensive medical care, it is a frequent source of nosocomial infection. The central line associated bloodstream infection (CLABSI) rate at our medical ICU had increased steadily, with an average rate between January and May 2011 of .47%. We used a cross-team approach to implement bundle care as a strategy to reduce the CLABSI rate. PURPOSE: We designed a project to reduce the CLABSI rate below .3% in our ICU. RESOLUTION: This project was conducted between June 2011 and May 2012. Our strategy included providing a sterile towel, implementing maximal barrier precautions (head to toe), designing an illustration explaining how to use 2% CHG, establishing a procedures and care checklist, implementing quality assurance for procedures and care, and providing education on bundle care. RESULTS: The CLABSI rate reduced to .24% after project implementation. This result was below the target of .30%. CONCLUSIONS: We want to share this experience to help other hospitals and units improve critical care quality and to continue working to achieve a zero-tolerance infection rate.

[Project to reduce the central venous catheter-related bloodstream infection rate].

BACKGROUND: Central venous catheter-related bloodstream infection (CRBSI) is an important indicator of care quality. The average CRBSI rate in our unit was 1.027% in 2009. Causes of infection included inadequate CRBSI prevention practices and outdated standard procedures. PURPOSE: We designed a project to reduce the CRBSI rate below 0.5% in our intensive care unit. RESOLUTION: Improvement plans included providing in-service education, establishing a central venous catheter (CVC) care checklist, and updating CRBSI clinical management standards. RESULTS: The CRBSI rate fell to 1.43‰ after implementation. This was significantly below the reduction target of 0.5%. CONCLUSIONS: This project effectively reduced CRBSI. We want to share this experience to help other hospitals and units improve critical care quality and reduce healthcare costs.

Inhibitory activity of kinetin on free radical formation of activated platelets in vitro and on thrombus formation in vivo.

Kinetin has been shown to have anti-aging effects on several different systems, including plants and human cells. Recently, we demonstrated that kinetin markedly inhibited platelet aggregation in washed human platelets. In the present study, an electron spin resonance (ESR) method was used to further evaluate the scavenging activity of kinetin on the free radicals formed. Kinetin (70 and 150 microM) concentration dependently reduced the ESR signal intensity of hydroxyl radicals in collagen (1 microg/ml)-activated platelets. Furthermore, kinetin was effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at doses of 4 and 6 mg/kg. In addition, intravenous injection of kinetin (4 and 6 mg/kg) significantly prolonged the bleeding time by approximately 1.9- and 2.1-fold as compared with normal saline in severed mesenteric arteries of rats. A continuous infusion of kinetin (0.6 mg/kg/min) for 10 min also significantly increased the bleeding time by about 2.3-fold, and the bleeding time returned to baseline within 120 min after cessation of kinetin infusion. Platelet thrombi formation was induced by irradiation of mesenteric venules with filtered light in mice pretreated intravenously with fluorescein sodium. When kinetin was administered at 13 and 14 mg/kg in mice pretreated with fluorescein sodium (5 mg/kg), the occlusion time was significantly prolonged. In conclusion, these results suggest that kinetin has effective free radical-scavenging activity in vitro and antithrombotic activity in vivo. Treatment with kinetin may lower the risk of thromboembolic-related disorders. Therefore, kinetin may be a potential therapeutic agent for arterial thrombosis, but its toxicity must be further assessed.