The association between ultrafiltration rate and mortality in a co- hort of chronic hemodialysis patients with and without diabetes mellitus: a 7-year retrospective observational study.

Background: The ultrafiltration rate (UFR) is one of the important factors involved in long-term mortality in hemodialysis (HD) patients. Presence of diabetes mellitus often affects UFR due to abrupt hypotension during dialysis. In this study, we aimed to find the optimal UFR to improve the mortality in this population with and without diabetes mellitus (DM).Methods: The effect of the UFR on mortality was retrospectively evaluated in 707 patients un- dergoing regular HD from 1 June 2010 to 30 June 2017. The relationship between the UFR and mortality in patients in the non-DM group and those in the DM group was evaluated. Logistic regression analyses were used to select the determinants of mortality. Receiver operating char- acteristic (ROC) curve analyses and survival analysis were used to determine the optimal cutoff points of UFR for mortality.Results: The cutoff UFR values of the non-DM and DM groups were 12.07 ml/hr/kg and 9.66 ml/ hr/kg, respectively. A survival curve showed that in the non-DM group, the 7-year survival rate of patients with a UFR <12.07 ml/hr/kg was 72.6% and that in those with a UFR ≥12.07 ml/hr/kg was 19.6% (p<0.0001). In the DM group, the 7-year survival rate of those with a UFR <9.66 ml/ hr/kg was 66.7%, and it was 33.4% in those with a UFR ≥9.66 ml/hr/kg (p<0.0001).Conclusion: Lower UFR is essential for the long-term mortality of HD patients, and optimal UFR would be different between patients with and without DM

Construction of Semisynthetic DNA–Protein Conjugates with Phi X174 Gene-A* Protein

DNA–protein conjugates have frequently been used as versatile molecular tools for a variety of applications in biotechnology to harness synergistic effects of DNA and protein functions. With applications for DNA–protein conjugates growing, easy-to-use and economical methods for the synthesis of DNA–protein conjugates are required. In this study, we developed a method for site-specific labeling of single-stranded DNA (ssDNA) to a recombinant protein of interest (POI) through the Gene-A* protein (Gene-A*) from bacteriophage phi X174, without any chemical modifications of ssDNA. Gene-A* protein is an enzyme that site-selectively cleaves an oligodeoxyribonucleotide (ODN) containing a Gene-A* recognition sequence, at which point a tyrosine residue of Gene-A* is bonded to the 5′-phosphoryl group of the cleavage site via a stable phosphotyrosine linkage. Here, we constructed three kinds of recombinant proteins fused to Gene-A*: N-terminally Gene-A*-fused enhanced green fluorescent protein (EGFP), C-terminally Gene-A*-fused EGFP, and N-terminally Gene-A*-fused firefly luciferase (FLuc). The reaction yields of DNA–protein conjugation catalyzed by the Gene-A* moiety reached 80–90% in the three proteins, and kinetic study revealed that the reaction achieved a steady state after 10 min. Moreover, dot blot analyses were performed to evaluate the hybridization and aptamer-forming ability of ssDNA conjugated to the Gene-A* moiety of a recombinant Gene-A*-FLuc protein. This study demonstrated that a strategy using recombinant proteins fused to Gene-A* could offer a versatile, rapid, easy-to-use, and economical platform for producing DNA–protein conjugates

Effect of hemoperfusion with hexadecyl-immobilized cellulose beads on myocardial fatty acid imaging in hemodialysis patients: a case series study

Abstract Background Hexadecyl-immobilized porous cellulose beads (HICBs) can be used to remove β2-microglobulin, as well as several inflammatory cytokines and free protein-binding uremic toxins (PBUTs). Interleukin-6 and PBUT levels have been associated with oxidative stress and/or cardiovascular disease. In this retrospective study, we investigated the potential of direct hemoperfusion with HICBs to improve impaired myocardial fatty acid imaging in hemodialysis patients. Method We evaluated 24 hemodialysis patients who did not undergo percutaneous coronary intervention or coronary artery bypass grafting during the observation period. Among these patients, 12 who had been treated using HICB columns for more than 4 years were assigned to the HICBs group (mean observation period, 61.9 ± 16.3 months), while the remaining patients who had never undergone treatment with HICB columns were assigned to the non-HICBs group (mean observation period, 58.0 ± 12.2 months). Impaired myocardial fatty acid metabolism was assessed by single-photon emission computed tomography (SPECT) using 123I-β-ethyliodophenyl pentadecanoic acid (BMIPP). Uptake on SPECT was graded in 17 segments on a 5-point scale (0, normal; 4, absent) and assessed as the BMIPP summed score (SS). Results While the HICBs group showed a lower mean β2-MG than the non-HICBs group, the other baseline clinical patient characteristics did not differ between the two groups. In the HICBs group, the second BMIPP SS was decreased significantly compared with the first BMIPP SS. A decrease in the BMIPP SS was observed in nine (75%) patients with the first BMIPP SS ≥ 6, and no change was observed in three patients with BMIPP SS ≤ 2. In the non-HICBs group, the second BMIPP SS was increased significantly compared with the first BMIPP SS. Conclusion The improvement in myocardial fatty acid imaging suggests an improvement in the impaired myocardial microcirculation. We suggest that the use of direct hemoperfusion with HICBs may have improved the impaired myocardial microcirculation in hemodialysis patient through the removal of protein-bound toxins and inflammatory cytokines and might contribute towards improving the survival of dialysis patients