Cardiac resynchronization therapy appears to offer benefit in pediatric and CHD patients who differ substantially from the adult populations in whom this therapy has been most thoroughly evaluated to date. Further studies looking at the long-term benefit of this therapy in this population are needed.

The COP9/signalosome (CSN) is known to remove the stimulatory NEDD8 modification from cullins. The activity of the fission yeast cullins Pcu1p and Pcu3p is dramatically stimulated when retrieved from csn mutants but inhibited by purified CSN. This inhibition is independent of cullin deneddylation but mediated by the CSN-associated deubiquitylating enzyme Ubp12p, which forms a complex with Pcu3p in a CSN-dependent manner. In ubp12 mutants, as in csn mutants, Pcu3p activity is stimulated. CSN is required for efficient targeting of Ubp12p to the nucleus, where both cullins reside. Finally, the CSN/Ubp12p pathway maintains the stability of the Pcu1p-associated substrate-specific adaptor protein Pop1p. We propose that CSN/Ubp12p-mediated deubiquitylation creates an environment for the safe de novo assembly of cullin complexes by counteracting the autocatalytic destruction of adaptor proteins.

During the 40-day and 3-month waiting periods in patients post-MI, the WCD successfully treated SCA in 1.4%, and the risk was highest in the first month of WCD use. The WCD may benefit individual patients selected for high risk of SCA early post-MI.

A reduction in compound muscle action potential (CMAP) amplitude and area following proximal versus distal stimulation is the accepted clinical hallmark of conduction block; however, quantitative criteria for determining conduction block remain ambiguous. In this study, digitized records of individual motor unit action potentials (MUAPs) elicited by incremental stimulation in vivo were arithmetically combined in a computer simulation of CMAP generation. Through simulation of possible phase interaction patterns of individual MUAPs, we have shown that abnormal temporal dispersion alone can produce reductions in CMAP area of up to 50%, values that are commonly thought to represent conduction block. Furthermore, by simulating conduction block without excessive temporal dispersion in defined subpopulations of axons, we have demonstrated the importance of the fastest conducting (largest MUAP) axons in determining CMAP amplitude and area. In conclusion, measurements of CMAP amplitude and area in determining conduction block may be misleading if there is significant abnormal temporal dispersion, and quantitation of the degree of conduction block is difficult without knowledge of which subpopulations of axons are affected.

In recent literature, surgically created hemodialysis (HD) arteriovenous fistulas (AVF) have high rates of primary failure. Endovascular treatment holds promise to salvage these fistulae. The outcomes of 119 patients who had a "failing to mature" AVF and presented for endovascular management were evaluated prospectively. All patients underwent a fistulogram. Stenotic lesions underwent balloon angioplasty, and accessory veins underwent obliteration. Technical success was determined immediately after the procedure. AVF salvage was determined by successful use during HD. Patients were followed up for 1 yr, during which primary and secondary AVF patency rates were measured. T he low prevalence of the arteriovenous fistula (AVF) among US hemodialysis (HD) patients (1,2) has initiated nationwide measures to increase AVF creation and prevalence (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Among these are providing educational programs, setting forth guidelines and goals (3,4), implementing multidisciplinary approaches (4 -9), encouraging preoperative venous mapping (14 -19), and asking surgeons to create AVF instead of arteriovenous grafts (AVG) (10 -21).Overall, an increase in AVF prevalence is occurring in the United States, albeit at a slow rate (14 -20). One impediment has been high primary failure rates, which in recent series ranged between 23 and 46% (9,(12)(13)(14). The use of ultrasound or other means of preoperative venous mapping is likely to decrease the incidence of primary AVF failures (14 -19). However, the increasing demand to create more fistulas may lead to their creation in borderline vessels, thereby increasing primary failure rates (21-23). Thus, salvage of these primary failures will be essential for increasing AVF prevalence in the United States.In our dedicated endovascular suite, we used percutaneous angioplasty and accessory vein obliteration in attempts to salvage fistulas with primary failure. Because most did not present with thrombosis, we elected to refer to their fistulas as "failing to mature." In this article, we report our initial success rates as well as follow-up on a series of 119 consecutive patients who were referred for salvage of their "failing to mature" AVF. Materials and Methods DefinitionsThe "failing to mature" AVF in our series was defined as an AVF that had been created for at least 8 wk but had not matured enough to allow successful cannulation or use during HD. This includes (1) fistulas that were never cannulated for HD be cause of obvious lack of maturity; (2) fistulas that failed first cannulation attempts and were abandoned; (3) fistulas that were cannulated successfully but could not be used because the blood flow was insufficient to sustain HD; this may have been because of high venous pressure or poor arterial inflow; and (4) fistulas that thrombosed before any attempts at HD. Juxta-arterial anastomosis segment refers to the initial 5 cm of the AVF starting at the arterial anastomosis. Peripheral vein refers to the venous outflow tract of t...