The Efficacy of Mirabegron for the Relief of Ureteral Stent-Related Symptoms

To investigate the efficacy of mirabegron for lower urinary tract symptoms in patients with an indwelling ureteral stent after ureterorenoscopic lithotripsy. This was a prospective follow-up study of 76 patients with stent-related symptoms (SRSs). Patients with upper urinary calculi who were pre-stented for > 2 weeks before lithotripsy were examined for the presence of SRSs by tests including the International Prostate Symptom Score (IPSS), OAB Symptom Score (OABSS), and urinary bother and pain measured by a Visual Analogue Scale (VAS) before lithotripsy. Mirabegron (50 mg/day) was prescribed post-lithotripsy for 2 weeks. SRSs were assessed at the time of stent removal. The IPSS scores improved significantly from 16.2 to 14.3 (p<0.001) and the IPSS-QoL scores decreased significantly from 5.0 to 4.6 (p=0.012). The OABSS scores improved significantly from 7.7 to 6.8 (p=0.006), and the urinary urgency scores (OABSS-Q3) decreased significantly from 3.24 to 2.68 (p<0.001). The number of nocturia episodes decreased significantly from 2.5 to 2.2 (p=0.045). Urinary bother and pain assessed by the VAS declined from 4.2 and 3.1 to 3.8 (p=0.15) and 2.5 (p=0.075), respectively. Mirabegron significantly improved SRSs and the number of nocturia episodes due to a ureteral stent

Suplatast tosilate alleviates nasal symptoms through the suppression of nuclear factor of activated T-cells-mediated IL-9 gene expression in toluene-2,4-diisocyanate-sensitized rats

Histamine H1 receptor (H1R) gene is upregulated in patients with pollinosis; its expression level is highly correlated with the nasal symptom severity. Antihistamines are widely used as allergy treatments because they inhibit histamine signaling by blocking H1R or suppressing H1R signaling as inverse agonists. However, long-term treatment with antihistamines does not completely resolve toluene-2,4-diisocyanate (TDI)-induced nasal symptoms, although it can decrease H1R gene expression to the basal level, suggesting additional signaling is responsible for the pathogenesis of the allergic symptoms. Here, we show that treatment with suplatast tosilate in combination with antihistamines markedly alleviates nasal symptoms in TDI-sensitized rats. Suplatast suppressed TDI-induced upregulation of IL-9 gene expression. Suplatast also suppressed ionomycin/phorbol-12-myristate-13-acetate-induced upregulation of IL-2 gene expression in Jurkat cells, in which calcineurin (CN)/nuclear factor of activated T-cells (NFAT) signaling is known to be involved. Immunoblot analysis demonstrated that suplatast inhibited binding of NFAT to DNA. Furthermore, suplatast suppressed ionomycin-induced IL-9 mRNA upregulation in RBL-2H3 cells, in which CN/NFAT signaling is also involved. These data suggest that suplatast suppressed NFAT-mediated IL-9 gene expression in TDI-sensitized rats and this might be the underlying mechanism of the therapeutic effects of combined therapy of suplatast with antihistamine

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

ANALYSIS OF REACHING MOVEMENTS WITH THE ADDITION OF RESISTANCE FORCES IN THE HORIZONTAL AND VERTICAL PLANES USING A ROBOT ARM IN NON-DISABLED INDIVIDUALS

A new, simpler, quantitative evaluation method, with higher reproducibility and validity than the conventional method used to evaluate hemiplegic upper extremities, is needed. The general properties of reaching movements were examined in healthy subjects by adding resistance forces to establish a new evaluation method using robotic technology. The subjects included 14 non-disabled males and 2 non-disabled females whose average age was 25 years. Their reaching movements were measured in both the horizontal and vertical planes with resistance force to add disturbance using a robot arm. Then, the jerk cost, the largest swinging distance, and the end¬point displacement were calculated. Significant differences were seen between subjects with and without disturbance in the horizontal jerk cost and largest swinging distance in the horizontal plane, and vertical jerk cost and largest swinging distance in the vertical plane. The horizontal and vertical jerk costs and largest swinging distances were also greater with a larger disturbance. In the reaching movements of healthy people in the horizontal and vertical planes, when the reaching movement was subjected to orthogonal disturbance, jerk cost and largest swinging distance in the direction of the disturbance were easily affected in response to the disturbance

Triammonium Molecular Tripods as Organic Building Blocks for Hybrid Perovskite Solar Cells

Considerable efforts have been devoted to the development of new organic‐inorganic hybrid perovskites as well as their passivation‐layer materials to improve the performance of solution‐processable thin‐film solar cells for practical applications. For this purpose, monocations, such as monoammonium ions, have been studied extensively as organic building blocks. Herein, a new class of cationic molecules featuring a triptycene framework is introduced, to which three ammonium ions are attached close to each other. Inspired by the previous finding that 1,8,13‐trisubstituted triptycenes have an excellent ability to form 2D assemblies, two derivatives with ammonium ion groups at these positions are synthesized, linked either directly or via methylene spacers. Hybrid perovskites with different dimensionalities in terms of the inorganic octahedral units were prepared by reaction of the triammonium‐appended triptycene tripods with PbI2, however, the optoelectronic properties obtained were unsatisfactory. Even so, the triammonium‐containing triptycene tripod having methylene spacers was shown to serve as a good passivation layer for perovskites solar cells (PSCs), leading to improvements in power conversion efficiency and long‐term stability. Given the large degree of design freedom, triptycene tripods merit further investigation as a new motif in the development of surface‐passivation materials for PSCs