Double-blind, placebo-controlled study of lurasidone monotherapy for the treatment of bipolar I depression.

AIM: Previous studies conducted primarily in the USA and Europe have demonstrated the efficacy and safety of lurasidone 20-120 mg/day for the treatment of bipolar I depression. The aim of the current study was to evaluate the efficacy and safety of lurasidone monotherapy for the treatment of bipolar I depression among patients from diverse ethnic backgrounds, including those from Japan. METHODS: Patients were randomly assigned to double-blind treatment for 6 weeks with lurasidone, 20-60 mg/day (n = 184) or 80-120 mg/day (n = 169), or placebo (n = 172). The primary end-point was change from baseline to Week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Lurasidone treatment significantly reduced mean MADRS total scores from baseline to Week 6 for the 20-60-mg/day group (-13.6; adjusted P = 0.007; effect size = 0.33), but not for the 80-120-mg/day group (-12.6; adjusted P = 0.057; effect size = 0.22) compared with placebo (-10.6). Treatment with lurasidone 20-60 mg/day also improved MADRS response rates, functional impairment, and anxiety symptoms. The most common adverse events associated with lurasidone were akathisia and nausea. Lurasidone treatments were associated with minimal changes in weight, lipids, and measures of glycemic control. CONCLUSION: Monotherapy with once daily doses of lurasidone 20-60 mg, but not 80-120 mg, significantly reduced depressive symptoms and improved functioning in patients with bipolar I depression. Results overall were consistent with previous studies, suggesting that lurasidone 20-60 mg/day is effective and safe in diverse ethnic populations, including Japanese.

Formation and Characterization of Hydrogen Boride Sheets Derived from MgB2 by Cation Exchange.

Two-dimensional (2D) materials are promising for applications in a wide range of fields because of their unique properties. Hydrogen boride sheets, a new 2D material recently predicted from theory, exhibit intriguing electronic and mechanical properties as well as hydrogen storage capacity. Here, we report the experimental realization of 2D hydrogen boride sheets with an empirical formula of H1B1, produced by exfoliation and complete ion-exchange between protons and magnesium cations in magnesium diboride (MgB2) with an average yield of 42.3% at room temperature. The sheets feature an sp2-bonded boron planar structure without any long-range order. A hexagonal boron network with bridge hydrogens is suggested as the possible local structure, where the absence of long-range order was ascribed to the presence of three different anisotropic domains originating from the 2-fold symmetry of the hydrogen positions against the 6-fold symmetry of the boron networks, based on X-ray diffraction, X-ray atomic pair distribution functions, electron diffraction, transmission electron microscopy, photo absorption, core-level binding energy data, infrared absorption, electron energy loss spectroscopy, and density functional theory calculations. The established cation-exchange method for metal diboride opens new avenues for the mass production of several types of boron-based 2D materials by countercation selection and functionalization.

Novel spliced variants of large-conductance Ca(2+)-activated K(+)-channel ß2-subunit in human and rodent pancreas.

Large-conductance Ca(2+)-activated K(+ )(BK) channel regulates action potential firing in pancreatic ß-cells. We cloned novel spliced variants of the BK-channel ß(2)-subunit (BKß2b), which consisted of 36 amino acids including the N-terminal in the original human BKß2 (BKß2a), from human and rodent pancreas. Real-time PCR analysis showed the abundant expression of BKß2b transcripts in human and rodent pancreas and also in the RINm5f insulinoma cell line. In addition, up-regulation of both BK-channel α-subunit (BKα) and BKß2b transcripts was observed in pancreas tissues from diabetes mellitus patients. In HEK293 cells co-expressing BKα and BKß2b, the inactivation of BK-channel currents, which is typical for BKα + BKß2a, was not observed, and electrophysiological and pharmacological properties of BKα + BKß2b were almost identical to those of BKα alone. In HEK293 cells stably expressing BKα, the transient co-expression of yellow fluorescence protein (YFP)-tagged BKß2a proteins resulted in their distribution along the cell membrane. In contrast, the co-expression of YFP-tagged BKß2b with BKα showed diffusely distributed fluorescence signals throughout the cell body. Taken together, the predominant splicing of BKß2b versus that of BKß2a presumably enhances the contribution of BK channels to membrane potential and may possibly be a factor modulating insulin secretion in a suppressive manner in pancreatic ß-cells.