No abstract

Circular RNA is more stable than linear RNA both in vitro and in vivo because of its inaccessibility to exoribonucleases. Therefore, circularization of functional RNAs is a potentially useful methodology for designing therapeutic RNA reagents. We designed a circular hammerhead ribozyme that can cleave the template region of human telomerase RNA. This circular hammerhead ribozyme was generated by in vitro transcription followed by spontaneous self-circularization activity using the permuted intron-exon (PIE) method. Two-dimensional gel electrophoresis and alkaline digestion of the in vitro transcription products revealed that the circular hammerhead ribozyme could be produced by the PIE method. The purified circular hammerhead ribozyme cleaved the template region of human telomerase RNA in a magnesium-dependent manner. These results indicated that the circular hammerhead ribozyme generated by the PIE method maintained the specific feature of canonical hammerhead catalytic activity.

Syncope is induced by various causes in Japan. It is important that we understand the characteristics of each syncope cause. The consent rate for implanting an ILR in appropriate unexplained syncope patients is low. We need to educate these patients about the importance of making a diagnosis of syncope.

Background:Although clinical trials demonstrate that the elderly with atrial fibrillation have risks of thrombosis and bleeding, the relationship between aging and coagulation fibrinolytic system in "real-world" cardiology outpatients is uncertain. Methods and Results:We retrospectively evaluated 773 patients (mean age: 58 years; 52% men; Asian ethnicity). To thoroughly investigate markers of coagulation and fibrinolysis, we simultaneously measured levels of D-dimer, prothrombin-fragment1+2 (F1+2), plasmin-α2 plasmin inhibitor complex (PIC), and thrombomodulin (TM). There were correlations between aging and levels of F1+2, D-dimer, PIC, and TM (R=0.61, 0.57, 0.49, and 0.30, respectively). We compared 3 age groups, which were defined as the Y group (<64 years), M group (65-74 years), and the O group (>75 years). Levels of markers were higher in older individuals (D-dimer: 1.0±0.8 vs. 0.8±0.8 vs. 0.6±0.4 μg/ml, F1+2: 281.8±151.3 vs. 224.6±107.1 vs. 155.5±90.0 pmol/L, PIC: 0.9±0.3 vs. 0.8±0.3 vs. 0.6±0.5 μg/ml, and TM: 2.9±0.8 vs. 2.7±0.7 vs. 2.5±0.7FU/ml). We performed logistic regression analysis to determine F1+2 and PIC levels. Multivariate analysis revealed that aging was the most important determinant of high F1+2 and PIC levels.Conclusions: Hypercoagulable states develop with advancing age in "real-world" cardiology outpatients. (Circ J 2016; 80: 2133 -2140

Background There are some controversial reports related to the pro‐arrhythmic or anti‐arrhythmic potential of cardiac resynchronization therapy (CRT) and little is known about the relationship between ventricular arrhythmia (VA) and left ventricular (LV)‐lead threshold. Hypothesis Upgrade CRT is anti‐arrhythmic effect of VA with implantable cardioverter‐defibrillator (ICD) patients and has a relationship with the incident of VA and LV‐lead threshold. Methods Among 384 patients with the implantation of CRT‐defibrillator (CRT‐D), 102 patients underwent an upgrade from ICD to CRT‐D. We divided patients into three groups; anti‐arrhythmic effect after upgrade (n = 22), pro‐arrhythmic effect (n = 14), and unchanging‐VA events (n = 66). The VA event was determined by device reports. We described the electrocardiography parameters, LV‐lead characteristics, and clinical outcomes. Results Before upgrade, the numbers of VA were 305 episodes and the numbers of ICD therapy were 157 episodes. While after upgrade, the numbers of VA were 193 episodes and the number of ICD therapy were 74 episodes. Ventricular tachycardia cycle length (VT‐CL) after upgrade was significantly slower as compared to those with before upgrade. Pro‐arrhythmic group was significantly higher with delta LV‐lead threshold (after 1 month—baseline) as compared to those with anti‐arrhythmic group (0.74 vs −0.21 V). Furthermore, pro‐arrhythmic group was significantly bigger with delta VT‐CL (after 3 months—before 3 months) as compared to those with anti‐arrhythmic group ( P = .03). Conclusions We described upgrade‐CRT was associated with reduction of VA, ICD therapies and VT‐CL. While 14 patients had a pro‐arrhythmic effect and LV lead threshold might be associated with VA‐incidents.