Prophylactic CMV therapy does not improve three‐yr patient and graft survival compared to preemptive therapy

Despite increasing evidence in favor of prophylactic valganciclovir treatment in kidney transplant recipients for the prevention of cytomegalovirus (CMV) infection, the impact of preemptive vs. prophylactic treatment on long‐term clinical outcomes is unclear. In this retrospective study, 187 kidney transplant recipients with serologic intermediate‐risk constellation (recipient CMV IgG positive) received either preemptive or prophylactic treatment with valganciclovir. Patient survival (primary endpoint), graft survival, viremia rates, and other CMV‐related outcomes were analyzed. Prophylactic therapy reduced the rates for CMV viremia during the first year (hazard ratio: 0.48, 95% confidence interval [CI] 0.30–0.75; p < 0.001). There was a trend for higher three‐yr patient mortality in the prophylactic group (hazard ratio: 5.08, 95% CI 0.62–41.3; p = 0.091), and the rate of graft loss was not reduced (hazard ratio: 0.93, 95% CI 0.32–2.68; p = 0.894). Estimated glomerular filtration rate over three yr was on average 6.8 mL/min/1.73 m² lower in the prophylactic group (95% CI −11.68 to −1.81; p = 0.007) using a multivariate random effects model but showed more improvement over time. Prophylactic valganciclovir treatment reduced the rate of CMV infections during the first year post‐transplant but no effects of prophylactic treatment on patient and graft survival or kidney function over three yr were observed.     

I know what I will see: action-specific motor preparation activity in a passive observation task

Literature on mirror neurons has shown that seeing someone preparing to move generates in the motor areas of the observers a brain activity similar to that generated when the subject prepares his own actions. Thus, the ‘mirroring’ of action would not be limited to the execution phase but also involves the preparation process. Here we confirm and extend this notion showing that, just as different brain activities prepare different voluntary actions, also different brain activities prepare to observe different predictable actions. Videos of two different actions from egocentric point of view were presented in separate blocks: (i) grasping of a cup and (ii) impossible grasping of a cup. Subjects had to passively observe the videos showing object-directed hand movements. Through the use of the event-related potentials, we found a cortical activity before observing the actions, which was very similar to the one recorded prior to the actual execution of that same action, in terms of both topography and latency. This anticipatory activity does not represent a general preparation state but an action-specific state, because being dependent on the specific meaning of the forthcoming action. These results reinforce our knowledge about the correspondence between action, perception and cognition.     

Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid–Resistant Nephrotic Syndrome

Background and objectives

Treatment of congenital nephrotic syndrome (CNS) and steroid–resistant nephrotic syndrome (SRNS) is demanding, and renal prognosis is poor. Numerous causative gene mutations have been identified in SRNS that affect the renal podocyte. In the era of high–throughput sequencing techniques, patients with nongenetic SRNS frequently escape the scientific interest. We here present the long-term data of the German CNS/SRNS Follow-Up Study, focusing on the response to cyclosporin A (CsA) in patients with nongenetic versus genetic disease.

Design, setting, participants, & measurements

Cross–sectional and longitudinal clinical data were collected from 231 patients with CNS/SRNS treated at eight university pediatric nephrology units with a median observation time of 113 months (interquartile range, 50–178). Genotyping was performed systematically in all patients.

Results

The overall mutation detection rate was high at 57% (97% in CNS and 41% in SRNS); 85% of all mutations were identified by the analysis of three single genes only (NPHS1, NPHS2, and WT1), accounting for 92% of all mutations in patients with CNS and 79% of all mutations in patients with SRNS. Remission of the disease in nongenetic SRNS was observed in 78% of patients after a median treatment period of 2.5 months; 82% of nongenetic patients responded within 6 months of therapy, and 98% of patients with nongenetic SRNS and CsA–induced complete remission (normalbuminemia and no proteinuria) maintained a normal renal function. Genetic SRNS, on the contrary, is associated with a high rate of ESRD in 66% of patients. Only 3% of patients with genetic SRNS experienced a complete remission and 16% of patients with genetic SRNS experienced a partial remission after CsA therapy.

Conclusions

The efficacy of CsA is high in nonhereditary SRNS, with an excellent prognosis of renal function in the large majority of patients. CsA should be given for a minimum period of 6 months in these patients with nongenetic SRNS. In genetic SRNS, response to CsA was low and restricted to exceptional patients.     

Different neural capacity limitations for articulatory and non-articulatory maintenance of verbal information

Many studies have demonstrated attenuated verbal working memory (WM) under articulatory suppression. However, performance is not completely abolished, suggesting a less efficient, non-articulatory mechanism for the maintenance of verbal information. The neural causes for the reduced efficiency of such a putative complementary maintenance system have not yet been addressed. The present study was conducted to fill this gap. Subjects performed a Sternberg task (a) under articulatory maintenance at low, high, and supracapacity set sizes and (b) under non-articulatory maintenance at low and high set sizes. With functional magnetic resonance imaging, set-size related increases in activity were compared between subvocal articulatory rehearsal and non-articulatory maintenance. First, the results replicate previous findings showing different networks underlying these two maintenance strategies. Second, activation of all key nodes of the articulatory maintenance network increased with the amount of memorized information, showing no plateau at high set sizes. In contrast, for non-articulatory maintenance, there was evidence for a plateau at high set sizes in all relevant areas of the network. Third, for articulatory maintenance, the non-articulatory maintenance network was additionally recruited at supracapacity set sizes, presumably to assist processing in this highly demanding condition. This is the first demonstration of differential neural bottlenecks for articulatory and non-articulatory maintenance. This study adds to our understanding of the performance differences between these two strategies supporting verbal WM.