Abstract:Patients considering renal transplantation face an increasingly complex array of choices as a result of the revised kidney transplant allocation system. Decision aids have been shown to improve patient decision making through the provision of detailed, relevant, individualized clinical data. A mobile iOS based application (app) including animated patient education and individualized risk adjusted outcomes following kidney transplants with varying donor characteristics and DSA waiting times was piloted in 2 large US transplant programs with a diverse group of renal transplant candidates (N=81).The majority (86%) of patients felt that the app improved their knowledge and was culturally appropriate for their race/ethnicity (67%-85%). Patients scored significantly higher on transplant knowledge testing (9.1/20 to 13.8/20 p<0.001) after viewing the app, including patients with low health literacy (8.0 to 13.0 p<0.001). Overall knowledge of and interest in living and deceased donor kidney transplantation increased. This pilot project confirmed the benefit and cultural acceptability of this educational tool, and further refinement will explore how to better communicate the risks and benefits of non-standard donors.

General DNA hypomethylation is associated with Alzheimer’s disease (AD), but it is unclear when DNA hypomethylation starts or plays a role in AD pathology or whether DNA re-methylation would rescue early amyloid-related cognitive impairments. In an APP transgenic mouse model of AD-like amyloid pathology we found that early intraneuronal amyloid beta build-up is sufficient to unleash a global and beta-site amyloid precursor protein cleaving enzyme 1 (bace-1) DNA demethylation in AD-vulnerable brain regions. S-adenosylmethionine administration at these early stages abolished this hypomethylation, diminished the amyloid pathology and restored cognitive capabilities. To assess a possible human significance of findings, we examined the methylation at 12 CpGs sites in the bace-1 promoter, using genome-wide DNA methylation data from 740 postmortem human brains. Thus, we found significant associations of bace-1 promoter methylation with β-amyloid load among persons with AD dementia, and PHFtau tangle density. Our results support a plausible causal role for the earliest amyloid beta accumulation to provoke DNA hypomethylation, influencing AD pathological outcomes.

Background The ongoing shortage of donor livers for transplantation and the increased use of marginal livers necessitate the development of accurate pretransplant tests of viability. Considering the importance energy status during transplantation, we aimed to correlate peritransplant energy cofactors to posttransplant outcome and subsequently model this in an ex vivo setting. Methods Sequential biopsies were taken from 19 donor livers postpreservation, as well as 30 min after portal venous (PVR) and hepatic arterial reperfusion (HAR) and analyzed by LC-MS for energetic cofactors (ATP/ADP/AMP, NADH/NAD+, NADPH/NADP+, FAD+, GSSG/GSH). Energy status was correlated to posttransplant outcome. In addition, 4 discarded human DCD livers were subjected to ex vivo reperfusion, modeling reperfusion injury and were similarly analyzed for energetic cofactors. Results A rapid shift towards higher energy adenine nucleotides was observed following clinical reperfusion, with a 2.45-, 3.17- and 2.12-fold increase in ATP:ADP, ATP:AMP and energy charge (EC) after PVR, respectively. Seven of the 19 grafts developed early allograft dysfunction (EAD). Correlation with peritransplant cofactors revealed a significant difference in EC between EAD and normal functioning grafts (0.09 vs. 0.31, P<0.05). In the simulated reperfusion model, a similar trend in adenine nucleotide changes was observed. Conclusion A preserved energy status appears critical in the peritransplant period. Levels of adenine nucleotides change rapidly following reperfusion and ratios of ATP/ADP/AMP following reperfusion are significantly correlated to graft function. Using these markers as a viability test in combination with ex vivo reperfusion may provide a useful predictor of outcome that incorporates donor, preservation and reperfusion factors.

No abstract