Comparative Evaluation of the Safety and Efficacy of Long-Term Use of Imidafenacin and Solifenacin in Patients with Overactive Bladder: A Prospective, Open, Randomized, Parallel-Group Trial (the LIST Study)

Objectives. Overactive bladder (OAB) is a chronic disease, but comparative trials of anticholinergics, which are commonly used for treatment of OAB, have generally been performed for up to 12 weeks only. There is no comparative study of a long-term intervention. Methods. We conducted a 52-week prospective randomized comparative study to evaluate the efficacy and tolerability of two anticholinergics. Results. Forty-one Japanese patients with untreated OAB were randomly assigned to imidafenacin and solifenacin groups. There was no difference in OABSS and KHQ scores between the two groups, but the severity and incidence of adverse events caused by the anticholinergics showed increased differences between the groups with time. The severity of dry mouth and the incidence of constipation were significantly lower in the imidafenacin group (P = 0.0092 and P = 0.0013, resp.). Conclusions. This study is the first long-term trial to show differences in the properties of anticholinergics that were not detected in short-term studies. Since OAB is a chronic disease, we conclude that imidafenacin is preferable to solifenacin from a perspective of safety

Suzaku Observation of Group of Galaxies NGC 507: Temperature and Metal Distributions in the Intra-cluster Medium

Temperature and abundance distributions of the intra-cluster medium (ICM) in the NGC 507 group of galaxies were studied with Suzaku. Observed concentric annular spectra were well-represented by a two temperature model for ICM, and we found steeper abundance gradients for Mg, Si, S, and Fe compared with O in the central region. Abundance ratios of alpha-elements to iron were found to be similar to those in other groups and poor clusters. We calculated metal mass-to-light ratios for Fe, O and Mg (IMLR, OMLR, MMLR) for NGC 507, and values for different systems were compared. Hotter and richer systems tend to show higher values of IMLR, OMLR, and MMLR. OMLR and MMLR were measured to an outer region for the first time with Suzaku, while IMLR was consistent with that with ASCA. We also looked into 2-dimensional map of the hardness ratio, but found no significant deviation from the circular symmetry.Comment: 12 pages, 10 figures, accepted for publication in PAS

Inhomogeneity in the Hot Intracluster Medium of Abell 1060 Observed with Chandra

A Chandra observation of the non-cooling flow cluster A 1060 has confirmed that the hot intracluster medium has fairly uniform distributions of temperature and metal abundance from a radius of about 230 kpc to the central 5 kpc region (H_0= 75 km/s/Mpc). The radial temperature profile shows a broad peak at 30-40 kpc from the center at a level ~20% higher than that in the outer region. Assuming spatially uniform temperature and abundance distributions, we derived a 3-dimensional density structure by iteratively correcting the beta model, and obtained the central gas density to be 8.2^{+1.8}_{-1.0} x 10^{-3} cm^{-3}. The distribution of gravitational mass was estimated from the density profile, and a central concentration of mass within a radius of 50 kpc was indicated. The data also suggest several high-abundance regions. The most significant blob adjacent to the central galaxy NGC 3311 has a radius of about 9 kpc, which indicates a metallicity of ~1.5 solar. We consider that this blob may be produced by the gas stripped off from NGC 3311.Comment: 10 pages, 11 figures, accepted by PASJ. High resolution version available at http://www-x.phys.metro-u.ac.jp/~akira_h/papers

A Unique Gene-Silencing Approach, Using an Intelligent RNA Expression Device (iRed), Results in Minimal Immune Stimulation When Given by Local Intrapleural Injection in Malignant Pleural Mesothelioma

Background: We have recently introduced an intelligent RNA expression device (iRed), comprising the minimum essential components needed to transcribe short hairpin RNA (shRNA) in cells. Use of iRed efficiently produced shRNA molecules after transfection into cells and alleviated the innate immune stimulation following intravenous injection. Methods: To study the usefulness of iRed for local injection, the engineered iRed encoding luciferase shRNA (Luc iRed), complexed with cationic liposomes (Luc iRed/liposome-complexes), was intrapleurally injected into an orthotopic mesothelioma mouse model. Results: Luc iRed/liposome-complexes markedly suppressed the expression of a luciferase marker gene in pleurally disseminated mesothelioma cells. The suppressive efficiency was correlated with the expression level of shRNA within the mesothelioma cells. In addition, intrapleural injection of iRed/liposome-complexes did not induce IL-6 production in the pleural space and consequently in the blood compartment, although plasmid DNA (pDNA) or dsDNA (the natural construct for iRed) in the formulation did. Conclusion: Local delivery of iRed could augment the in vivo gene silencing effect without eliciting pronounced innate immune stimulation. Our results might hold promise for widespread utilization of iRed as an RNAi-based therapeutic for intracelial malignant cancers

A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease

Background: Kawasaki disease (KD) is a systemic vasculitis which may be associated with coronary artery aneurysms. A notable risk factor for the development of coronary artery aneurysms is resistance to intravenous immunoglobulin (IVIG) therapy, which comprises standard treatment for the acute phase of KD. The cause of IVIG resistance in KD is largely unknown; however, the contribution of genetic factors, especially variants in immune-related genes, has been suspected. Methods: To explore genetic variants related to IVIG-unresponsiveness, we designated KD patients who did not respond to both first and second courses of IVIG therapy as IVIG-unresponsive patients. Using genomic DNA from 30 IVIG-unresponsive KD patients, we performed pooled genome sequencing targeting 39 immune-related cytokine receptor genes. Results: The single nucleotide variant (SNV), rs563535954 (located in the IL4R locus), was concentrated in IVIG-unresponsive KD patients. Individual genotyping showed that the minor allele of rs563535954 was present in 4/33 patients with IVIG-unresponsive KD, compared with 20/1063 individuals in the Japanese genome variation database (odds ratio = 7.19, 95% confidence interval 2.43-21.47). Furthermore, the minor allele of rs563535954 was absent in 42 KD patients who responded to IVIG treatment (P = 0.0337), indicating that a low-frequency variant, rs563535954, is associated with IVIG-unresponsiveness in KD patients. Although rs563535954 is located in the 3'-untranslated region of IL4R, there was no alternation in IL4R expression associated with the mior allele of rs563535954. However, IVIG-unresponsive patients that exhibited the minor allele of rs563535954 tended to be classified into the low-risk group (based on previously reported risk scores) for prediction of IVIG-resistance. Therefore, IVIG-unresponsiveness associated with the minor allele of rs563535954 might differ from IVIG-unresponsiveness associated with previous risk factors used to evaluate IVIG-unresponsiveness in KD. Conclusion: These findings suggest that the SNV rs563535954 could serve as a predictive indicator of IVIG-unresponsiveness, thereby improving the sensitivity of risk scoring systems, and may aid in prevention of coronary artery lesions in KD patients.ArticlePEDIATRIC RHEUMATOLOGY.17:34(2019)journal articl