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Matthew A. Summers Emily R. Vasiljevski Kathy Mikulec Lauren Peacock David G. Little Aaron Schindeler 《Molecular genetics and metabolism》2018,123(4):518-525
Neurofibromatosis Type 1 (NF1) is a common autosomal dominant genetic disorder While NF1 is primarily associated with predisposition for tumor formation, muscle weakness has emerged as having a significant impact on quality of life. NF1 inactivation is linked with a canonical upregulation Ras-MEK-ERK signaling. This in this study we tested the capacity of the small molecule MEK inhibitor PD0325901 to influence the intramyocellular lipid accumulation associated with NF1 deficiency. Established murine models of tissue specific Nf1 deletion in skeletal muscle (Nf1MyoD?/?) and limb mesenchyme (Nf1Prx1?/?) were tested.Developmental PD0325901 dosing of dams pregnant with Nf1MyoD?/? progeny rescued the phenotype of day 3 pups including body weight and lipid accumulation by Oil Red O staining. In contrast, PD0325901 treatment of 4?week old Nf1Prx1?/? mice for 8?weeks had no impact on body weight, muscle wet weight, activity, or intramyocellular lipid. Examination of day 3 Nf1Prx1?/? pups showed differences between the two tissue-specific knockout strains, with lipid staining greatest in Nf1MyoD?/? mice, and fibrosis higher in Nf1Prx1?/? mice.These data show that a MEK/ERK dependent mechanism underlies NF1 muscle metabolism during development. However, crosstalk from Nf1-deficient non-muscle mesenchymal cells may impact upon muscle metabolism and fibrosis in neonatal and mature myofibers. 相似文献
995.
Emily Pao Nancy E. Gove Joseph T. Flynn Sangeeta Hingorani 《Biology of blood and marrow transplantation》2018,24(8):1678-1684
Hematopoietic cell transplantation (HCT) is a common treatment for many disorders. Albuminuria post-HCT, which may represent endothelial injury or inflammation from graft- versus-host disease, increases the risk of chronic kidney disease and nonrelapse mortality at 1 year. HCT recipients also have abnormal blood pressure (BP) and increased rates of cardiovascular complications. We sought to determine the relationships among albuminuria, endothelial dysfunction, and BP in HCT recipients. Patients age ?≥12 years who underwent their first allogeneic HCT between 2012 and 2015 and survived through day 80 post-HCT were eligible. Peripheral endothelial function was assessed using the EndoPAT2000 device at day 80 along with 24-hour ambulatory BP monitoring (ABPM). Clinical and laboratory data were collected along with a urine sample for calculation of the albumin-to-creatinine ratio. Both logistic and linear regression analyses were used to identify associations between EndoPAT score and clinical variables. Sixty patients (median age, 48 years; range, 14 to 69 years) completed the study. The median EndoPAT score was 2.05 (range, 1.02 to 4.45), and 17 patients (28%) had abnormal endothelial function. Forty-two patients (72%) had ambulatory hypertension (HTN), and 38 (63%) had blunted nocturnal dipping. HTN on ABPM (P?=?.045) and blunted nocturnal dipping (P?=?.04) were associated with a lower EndoPAT score. Albuminuria was not associated with EndoPAT score. There was a lack of agreement between our clinical definition of HTN (office BP and/or use of medications) and ABPM results (P?=?.04). We did not find an association between lower EndoPAT scores and albuminuria, but did find an association between an abnormal nocturnal dip and HTN diagnosed by ABPM. This suggests that albuminuria may reflect local endothelial injury and inflammation rather than a systemic process. Office BP readings do not accurately reflect true BP, suggesting that 24-hour ABPM studies are needed to diagnose and treat HTN appropriately. 相似文献
996.
Neal J. Thomas Debbie Spear Emily Wasserman Steven Pon Barry Markovitz Aalok R. Singh Simon Li Shira J. Gertz Courtney M. Rowan Allen Kunselman Robert F. Tamburro 《Biology of blood and marrow transplantation》2018,24(12):2479-2486
To assess if calfactant reduces mortality among children with leukemia/lymphoma or after hematopoietic cell transplantation (HCT) with pediatric acute respiratory distress syndrome (PARDS), we conducted a multicenter, randomized, placebo-controlled, double-blinded trial in 17 pediatric intensive care units (PICUs) of tertiary care children's hospitals. Patients ages 18 months to 25 years with leukemia/lymphoma or having undergone HCT who required invasive mechanical ventilation for bilateral lung disease with an oxygenation index (OI) > 10 and <37 were studied. Interventions used were intratracheal instillation of either calfactant or air placebo (1 or 2 doses). Forty-three subjects were enrolled between November 2010 and June 2015: 26 assigned to calfactant and 17 to placebo. There were no significant differences in the primary outcome, which was survival to PICU discharge (adjusted hazard ratio of mortality for calfactant versus placebo, 1.78; 95% confidence interval, .53 to 6.05; P?=?.35), OI, functional outcomes, or ventilator-free days, adjusting for risk strata and Pediatric Risk of Mortality (PRISM) score. Despite the risk-stratified randomization, more allogeneic HCT patients received calfactant (76% and 39%, respectively) due to low recruitment at various sites. This imbalance is important because independent of treatment arm and while adjusting for PRISM score, those with allogeneic HCT had a nonsignificant higher likelihood of death at PICU discharge (adjusted odds ratio, 3.02; 95% confidence interval, .76 to 12.06; P?=?.12). Overall, 86% of the patients who survived to PICU discharge also were successfully discharged from the hospital. These data do not support the use of calfactant among this high mortality group of pediatric leukemia/lymphoma and/or HCT patients with PARDS to increase survival. In spite of poor enrollment, allogeneic HCT patients with PARDS appeared to be characterized by higher mortality than even other high-risk immunosuppressed groups. Conducting research among these children is challenging but necessary, because survival to PICU discharge usually results in successful discharge to home. 相似文献
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Virtual reality (VR) technology is rapidly becoming a popular application for physical rehabilitation and motor control research.
But questions remain about whether this technology really extends our ability to influence the nervous system or whether moving
within a virtual environment just motivates the individual to perform. I served as guest editor of this month's issue of the
Journal of NeuroEngineering and Rehabilitation (JNER) for a group of papers on augmented and virtual reality in rehabilitation.
These papers demonstrate a variety of approaches taken for applying VR technology to physical rehabilitation. The papers by
Kenyon et al. and Sparto et al. address critical questions about how this technology can be applied to physical rehabilitation
and research. The papers by Sveistrup and Viau et al. explore whether action within a virtual environment is equivalent to
motor performance within the physical environment. Finally, papers by Riva et al. and Weiss et al. discuss the important characteristics
of a virtual environment that will be most effective for obtaining changes in the motor system. 相似文献
999.
Nicholas G. Moon Fiorella Mazzini Allison M. Pekkanen Emily M. Wilts Timothy E. Long 《Macromolecular chemistry and physics.》2018,219(16)
The monomer isosorbide diacrylate (iSDA) and commercially available dithiols allowed access to a range of biosourced, degradable polymers. Altering the dithiol identity significantly affected the glass transition Tgs of the polymer products; however, polymers did not exhibit Tgs above room temperature. Incorporating the comonomer N,N′‐methylene bisacrylamide provided mechanical reinforcement through hydrogen bonding, resulting in soft, pliable materials. Differential scannin calorimetry (DSC) and variable‐temperature fourier‐transform infrared (FTIR) spectroscopy indicated that increases in mechanical integrity resulted from hydrogen bonding. Dynamic mechanical analysis (DMA) revealed materials that exhibited suitable moduli and service windows at body temperature. Biological evaluation demonstrated favorable cytotoxicity and cell attachment, rendering these materials potential candidates as novel scaffold materials for tissue growth. 相似文献
1000.
Emily Kay-Rivest Marco A. Mascarella Pramod Puligandla Sherif Emil Christine Saint-Martin Lily H.P. Nguyen Sam J. Daniel Robert Baird 《Journal of pediatric surgery》2018,53(5):1010-1013