Rooneymcdonald0244

2-6.4%, R1f = 0.6-1.4%) for all readouts. Overall, SIR-TFE parameters exhibited the lowest variability, while SIR-EPI parameters were adversely affected by susceptibility-related image distortions. In patients with relapsing remitting multiple sclerosis (n = 2), focal changes in SIR parameters were observed in lesions using all three readouts; however, contrast was reduced in smaller lesions for SIR-TFE, which was consistent with the numerical simulations. Together, these findings demonstrate that efficient, accurate, and repeatable whole-brain SIR can be performed using 3D TFE, EPI, or TSE readouts; however, the appropriate readout should be tailored to the application. OBJECTIVE To evaluate economic costs from the health system perspective of an electronic health record-based clinical decision support (CDS) tool, TeenBP, designed to assist in the recognition and management of hypertension in youth. METHODS Twenty primary care clinics within an integrated health system were randomized to the TeenBP CDS or usual care (UC), with patient enrollment from 4/15/14-4/14/16. The 12-month change in standardized medical care costs for insured patients aged 10-17 years without prior hypertension were calculated for each study arm. The primary analysis compared patients with ≥1 visit with blood pressure (BP) ≥95th percentile (isolated hypertensive BP), and secondary analyses compared patients with ≥3 visits within one year with BP ≥95th percentile (incident hypertension). Generalized estimating equation models estimated the difference-in-differences in costs between groups over time. RESULTS Among 925 insured patients with an isolated hypertensive BP, the pre-to-post change in overall costs averaged $22 more for TeenBP CDS versus UC patients over 12 months, but this difference was not statistically significant (p=0.723). Among 159 insured patients with incident hypertension, the pre-to-post change in overall costs over 12 months was higher by $227 per person on average for TeenBP CDS versus UC patients, but this difference also was not statistically significant (p=0.313). CONCLUSIONS The TeenBP CDS intervention was previously found to significantly improve identification and management of hypertensive BP in youth, and in this study, we find that this tool did not significantly increase care costs in its first 12 months of clinical use. Elucidating the effects of nanoparticles (NPs) on key bacterial functions not only deepens our understanding of nano-toxicity mechanisms, but also guides us in the design criteria for manufacturing safe nanomaterials. In this study, bacterial growth, biofilm development and the expression of biofilm-related genes were monitored in Pseudomonas putida KT2440, a plant-beneficial bacterium, following exposure to ZnO NPs. Low concentrations of NPs (0.5-30 mg L-1) significantly promoted bacterial growth and biofilm formation, while higher concentrations (>30 mg L-1) significantly inhibited biofilm formation. Confocal laser scanning microscopy revealed that microscope slides coated with 0.5 mg L-1 of ZnO NPs showed enhanced bacterial colonization and biomass production, but at higher concentrations (250 mg L-1), biomass production was about 11 times lower than that of the substrate without NPs. Increased protein and sugar contents of the biofilm matrix corroborated the stimulating effects of low concentrations of ZnO NPs. Physiological data were supported by changes in the expression of genes associated with oxidative stress and biofilm development. ZnO NPs at 0.5 mg L-1 stimulated the expression of quorum sensing, lipopolysaccharide biosynthesis, and antibiotic resistance genes; high concentrations of ZnO NPs (250 mg L-1) down-regulated biofilm formation-related genes and up-regulated antioxidant genes. Our results indicate that long-term release of low concentrations of ZnO NPs to the environment would promote undesired biofilm formation and increased resistance to antibiotics. Akt inhibitor Silymarin extracted from milk thistle seeds, is used for treating hepatic diseases. Silybin and isosilybin are its main components, and synthesized from coupling of taxifolin and coniferyl alcohol. Here, the biosynthetic pathways of taxifolin and coniferyl alcohol were reconstructed in Saccharomyces cerevisiae for the first time. To alleviate substantial burden caused by a great deal of genetic manipulation, expression of the enzymes (e.g. ZWF1, TYR1 and ARO8) playing multiple roles in the relevant biosynthetic pathways was selectively optimized. The strain YT1035 overexpressing seven heterologous enzymes and five native enzymes and the strain YC1053 overexpressing seven heterologous enzymes and four native enzymes, respectively produce 336.8 mg/L taxifolin and 201.1 mg/L coniferyl alcohol. Silybin and isosilybin are synthesized from taxifolin and coniferyl alcohol under catalysis of APX1t (the truncated milk thistle peroxidase), with a yield of 62.5%. This study demonstrates an approach for producing silybin and isosilybin from glucose for the first time. Chronic kidney disease (CKD) is associated with elevated circulating fibroblast growth factor 23 (FGF23), impaired renal biosynthesis of 1α,25-dihydroxyvitamin D (1α,25(OH)2D), low bone mass, and increased fracture risk. Our previous data with human mesenchymal stem cells (hMSCs) indicated that vitamin D metabolism in hMSCs is regulated as it is in the kidney and promotes osteoblastogenesis in an autocrine/paracrine manner. In this study, we tested the hypothesis that FGF23 inhibits vitamin D metabolism and action in hMSCs. hMSCs were isolated from discarded marrow during hip arthroplasty, including two subjects receiving hemodialysis and a series of 20 subjects (aged 49-83 years) with estimated glomerular filtration rate (eGFR) data. The direct in vitro effects of rhFGF23 on hMSCs were analyzed by RT-PCR, Western immunoblot, and biochemical assays. Ex vivo analyses showed positive correlations for both secreted and membrane-bound αKlotho gene expression in hMSCs with eGFR of the subjects from whom hMSCs were isolated. There was downregulated constitutive expression of αKlotho, but not FGFR1 in hMSCs obtained from two hemodialysis subjects. In vitro, rhFGF23 countered vitamin D-stimulated osteoblast differentiation of hMSCs by reducing the vitamin D receptor, CYP27B1/1α-hydroxylase, biosynthesis of 1α,25(OH)2D3, and signaling through BMP-7. These data demonstrate that dysregulated vitamin D metabolism in hMSCs may contribute to impaired osteoblastogenesis and altered bone and mineral metabolism in CKD subjects due to elevated FGF23. This supports the importance of intracellular vitamin D metabolism in autocrine/paracrine regulation of osteoblast differentiation in hMSCs.