Identifying the molecular targets for the beneficial or detrimental effects of small-molecule drugs is an important and currently unmet challenge. We have developed a method, drug affinity responsive target stability (DARTS), which takes advantage of a reduction in the protease susceptibility of the target protein upon drug binding. DARTS is universally applicable because it requires no modification of the drug and is independent of the mechanism of drug action. We demonstrate use of DARTS to identify known small-molecule-protein interactions and to reveal the eukaryotic translation initiation machinery as a molecular target for the longevity-enhancing plant natural product resveratrol. We envisage that DARTS will also be useful in global mapping of protein-metabolite interaction networks and in label-free screening of unlimited varieties of compounds for development as molecular imaging agents.aging ͉ label-free ͉ proteomics ͉ small molecules

Exercises after arteriovenous fistula (AVF) creation may help to improve maturation; however, their usefulness has only been examined in indirect, non-comparative studies or small trials. Between June 2013 and November 2014, we included all ambulatory patients with stages 5-5D chronic kidney disease who were candidates for the creation of a native AVF in our center. After surgery, all patients were randomized to an exercise group or a control group with single-blind control. At 1 month postoperatively, clinical maturation (expert nurse inspection) and ultrasonographic maturation (flow >500 mL/min, venous diameter >5 mm and depth <6 mm) were assessed in all patients. A total of 72 patients were randomized, 3 were lost to follow-up, and 69 were finally analyzed. The mean age was 66.8 years (standard deviation 13.8), 70.0% were men, and 65.2% were in pre-dialysis. After surgery (42.0% had distal AVF), the patients were randomized (31 controls, 38 exercise group). At 1 month after surgery, global clinical and ultrasonographic maturation was assessed in 88.4% and 78.3% of AVF, respectively (kappa = 0.539). Non-significant differences in clinical or ultrasonographic maturation were seen between exercise and control group (94.7% vs. 80.6%, P = 0.069; 81.6% vs. 74.2%, P = 0.459). A stepwise logistic regression was performed to control previously analyzed asymmetrically distributed confounding factors (AVF localization), revealing that the exercise group showed greater clinical, but not ultrasonographic, maturation (odds ratio [OR] 5.861, 95% confidence interval: 1.006-34.146 and OR 2.403, 0.66-8.754). A postoperative controlled exercise program after AVF creation seems to increase 1-month clinical AVF maturation in distal accesses. Furthermore, exercise programs should be taken into account, especially in distal accesses.

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Percutaneous mechanical thrombectomy with AngioJet is a safe technique with a high-clinical success rate. The presence of residual thrombus after thrombectomy and early re-occlusions are related to poorer results.

Thoracoscopic pulmonary vein isolation in patients with previously unsuccessful catheter ablations demonstrates satisfactory sinus rhythm maintenance rates in paroxysmal and persistent atrial fibrillation, but not in long-standing persistent atrial fibrillation. As with other minimally invasive surgical techniques, there is an important learning curve.