On dialysis, HCVAb+ve patients had a slightly worse outcome. After renal transplantation, the HCVAb+ve cohort had a markedly worse patient and graft outcome. The impact of viral eradication on these outcomes is unknown.

We have studied the Sphingosine 1-phosphate (S1P) receptor system to better understand why certain molecular targets within a closely related family are much more tractable when identifying compelling chemical leads. Five medically important G protein-coupled receptors for S1P regulate heart rate, coronary artery caliber, endothelial barrier integrity, and lymphocyte trafficking. Selective S1P receptor agonist probes would be of great utility to study receptor subtype-specific function. Through systematic screening of the same libraries, we identified novel selective agonists chemotypes for each of the S1P1 and S1P3 receptors. uHTS for S1P1 was more effective than for S1P3, with many selective, low nanomolar hits of proven mechanism emerging for. Receptor structure modeling and ligand docking reveal differences between the receptor binding pockets, which are the basis for sub-type selectivity. Novel selective agonists interact primarily in the hydrophobic pocket of the receptor in the absence of head-group interactions. Chemistry-space and shape-based analysis of the screening libraries in combination with the binding models explain the observed differential hit rates and enhanced efficiency for lead discovery for S1P1 vs. S1P3 in this closely related receptor family.

The current definition of a significant stenosis in an autologous arteriovenous fistula (aAVF), the percentage narrowing compared with the adjacent "normal" vessel, is inaccurate. We believe a significant stenosis in the aAVF is an absolute minimal luminal diameter determined by the requirements of the hemodialysis pump. To determine what absolute diameter constitutes a hemodynamically significant stenosis in a radio-cephalic autologous arteriovenous fistula (RC aAVF), the minimal luminal diameter of dysfunctional RC aAVF was compared to that of functional RC aAVF using grayscale and color ultrasound. There were 93 fistulas in study group and 77 in control group. The mean minimum luminal diameter in study group was significantly lower than in control group (2.19 vs. 4.71 mm, p 0.001). With a cutoff value of 2.7 mm, there was 90% sensitivity and 80% specificity in distinguishing functional fistula from dysfunctional fistula. The area under the receiver-operator curve was 90% (CI 84-94%), indicating that a 2.7 mm diameter is accurate in discriminating functional from dysfunctional fistulas. An absolute minimal luminal diameter of 2.7 mm, as determined with grayscale and color ultrasound, is a useful cutoff for defining significant stenosis in a RC aAVF.

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