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Hidenori Maruyama,1 Fumiya Sano,2 Reiko Sakaguchi,3 Keisuke Okamoto,4 Itaru Miura5 1Medical Science, Sumitomo Pharma Co., Ltd, Osaka, Japan; 2Department of Data Science, Drug Development Division, Sumitomo Pharma Co., Ltd, Tokyo, Japan; 3Department of Clinical Research, Drug Development Division, Sumitomo Pharma Co., Ltd, Tokyo, Japan; 4Department of Clinical Operation, Drug Development Division, Sumitomo Pharma Co., Ltd, Tokyo, Japan; 5Department of Neuropsychiatry, Fukushima Medical University, Fukushima, JapanCorrespondence: Hidenori Maruyama, Tel +81-80-4368-2576, Fax +81-6-6203-5733, Email hidenori.maruyama@sumitomo-pharma.co.jpPurpose: To evaluate the effect of lurasidone on a new, patient Life Engagement scale in schizophrenia.Patients and Methods: This post-hoc analysis included participants (ages 18 to 74) diagnosed with schizophrenia who were randomized to lurasidone (40 mg/day) or placebo in a 6-week double-blind efficacy study and those who continued in a subsequent 12-week open-label extension study during which patients received either 40 or 80/mg day lurasidone (flexibly dosed). Change in life engagement was measured using the Positive and Negative Syndrome Scale (PANSS) 11-item Life Engagement subscale score, and individual subscale items, at week 6 during the double-blind phase and extension phase week 12 during the open-label extension phase.Results: Analysis focused on 478 subjects randomized to lurasidone or placebo during the 6-week trial, and 146 who received lurasidone during the extension phase. During the 6-week trial, there was a significantly greater change on the PANSS11 Life Engagement subscale score from baseline to week 6 in the lurasidone group compared to the placebo group (mean changes of − 6.4 and − 4.8, respectively, p = 0.006; effect size = 0.27). Further improvement was evident during the extension phase for patients who received lurasidone in both phases, with a mean change from double-blind baseline to week 12 of the open

Auto-fluorescent protein (AFP)-based biosensors transduce the structural change in their embedded recognition modules induced by recognition/reaction events to fluorescence signal changes of AFP. The lack of detailed structural information on the recognition module often makes it difficult to optimize AFP-based biosensors. To enhance the signal response derived from detecting the putative structural change in the nitric oxide (NO)-sensing segment of transient receptor potential canonical 5 (TRPC5) fused to enhanced green fluorescent protein (EGFP), EGFP-TRPC5, a facile two-step screening strategy, in silico first and in vitro second, was applied to variants of EGFP-TRPC5 deletion-mutated within the recognition module. In in silico screening, the structural changes of the recognition modules were evaluated as root-mean-square-deviation (RMSD) values, and 10 candidates were efficiently selected from 47 derivatives. Through in vitro screening, four mutants were identified that showed a larger change in signal response than the parent EGFP-TRPC5. One mutant in particular, 551-575, showed four times larger change upon reaction with NO and H₂O₂. Furthermore, mutant 551-575 also showed a signal response upon reaction with H₂O₂ in mammalian HEK293 cells, indicating that the mutant has the potential to be applied as a biosensor for cell measurement. Therefore, this two-step screening method effectively allows the selection of AFP-based biosensors with sufficiently enhanced signal responses for application in mammalian cells.

Objectives: To evaluate the short-term efficacy and safety of blonanserin in adolescents with schizophrenia.Methods: This 6-week multicenter, double-blind, randomized, placebo-controlled study investigated fixed-dose blonanserin (8 or 16 mg/day) in patients 12-18 years of age diagnosed with schizophrenia, as indicated by a Positive and Negative Syndrome Scale (PANSS) total score of 60-120 and a Clinical Global Impressions-Severity score of >= 3. The primary endpoint was change from baseline to week 6 in the PANSS total score, using a mixed model for repeated measures analysis. Safety was assessed by the incidence and severity of adverse events (AEs).Results: Among 151 randomized patients, 150 were included in the primary analysis population. Demographic and clinical characteristics were similar across groups at baseline. The rate of study discontinuation was 14.9%, 23.5%, and 28.3% in patients administered with placebo, blonanserin 8 mg/day, and blonanserin 16 mg/day, respectively. The least-squares mean change (95% confidence interval [CI]) from baseline to week 6 in PANSS total score was -10.6 (-16.10 to -5.10), -15.3 (-20.80 to -9.86), and -20.5 (-25.89 to -15.16) in patients administered placebo, 8 mg/day blonanserin, and 16 mg/day blonanserin, respectively. The 16-mg/day blonanserin group showed significantly greater reduction in the PANSS total score than the placebo group (least-squares mean difference [95% CI]: -9.9 [-17.61 to -2.25], p = 0.012, effect size: 0.538), although the 8-mg/day group showed no significant difference. The incidence of AEs such as akathisia, somnolence, and hyperprolactinemia was higher in the blonanserin groups than in the placebo group. AEs associated with blonanserin were generally mild and were consistent with its known profile in adults with schizophrenia.Conclusions: Blonanserin achieved a sufficient efficacy in adolescent patients, and the safety profile was similar to that in adults, which suggests that blonanserin may be a s

Objectives: To evaluate the short-term efficacy and safety of blonanserin in adolescents with schizophrenia.Methods: This 6-week multicenter, double-blind, randomized, placebo-controlled study investigated fixed-dose blonanserin (8 or 16 mg/day) in patients 12-18 years of age diagnosed with schizophrenia, as indicated by a Positive and Negative Syndrome Scale (PANSS) total score of 60-120 and a Clinical Global Impressions-Severity score of >= 3. The primary endpoint was change from baseline to week 6 in the PANSS total score, using a mixed model for repeated measures analysis. Safety was assessed by the incidence and severity of adverse events (AEs).Results: Among 151 randomized patients, 150 were included in the primary analysis population. Demographic and clinical characteristics were similar across groups at baseline. The rate of study discontinuation was 14.9%, 23.5%, and 28.3% in patients administered with placebo, blonanserin 8 mg/day, and blonanserin 16 mg/day, respectively. The least-squares mean change (95% confidence interval [CI]) from baseline to week 6 in PANSS total score was -10.6 (-16.10 to -5.10), -15.3 (-20.80 to -9.86), and -20.5 (-25.89 to -15.16) in patients administered placebo, 8 mg/day blonanserin, and 16 mg/day blonanserin, respectively. The 16-mg/day blonanserin group showed significantly greater reduction in the PANSS total score than the placebo group (least-squares mean difference [95% CI]: -9.9 [-17.61 to -2.25], p = 0.012, effect size: 0.538), although the 8-mg/day group showed no significant difference. The incidence of AEs such as akathisia, somnolence, and hyperprolactinemia was higher in the blonanserin groups than in the placebo group. AEs associated with blonanserin were generally mild and were consistent with its known profile in adults with schizophrenia.Conclusions: Blonanserin achieved a sufficient efficacy in adolescent patients, and the safety profile was similar to that in adults, which suggests that blonanserin may be

We report the synthesis of photoactive carbon monoxide-releasing coordination polymer particles through the assembly of Mn(I) carbonyl complexes with bis(imidazole) ligands. The use of Mn(I) carbonyl complexes as metallic nodes in the coordination network avoids the potential for aggregation-induced self-quenching, favouring their use in the solid state.

Itaru Miura,1 Kei Watabe,2 Reiko Sakaguchi,3 Keisuke Okamoto,4 Hidenori Maruyama5 1Department of Neuropsychiatry, Fukushima Medical University, Fukushima, Japan; 2Department of Data Science, Drug Development Division, Sumitomo Pharma Co., Ltd, Tokyo, Japan; 3Department of Clinical Research, Drug Development Division, Sumitomo Pharma Co., Ltd, Tokyo, Japan; 4Department of Clinical Operation, Drug Development Division, Sumitomo Pharma Co., Ltd, Tokyo, Japan; 5Medical Affairs, Sumitomo Pharma Co., Ltd, Tokyo, JapanCorrespondence: Itaru Miura, Department of Neuropsychiatry, Fukushima Medical University 1 Hikarigaoka, Fukushima, 960-1295, Japan, Tel +81-24-547-1331, Fax +81-24-548-6735, Email itaru@fmu.ac.jpPurpose: To evaluate the effectiveness and safety of lurasidone 80 mg/day (versus the 40 mg/day dose) during a 12-week, open-label extension study in patients with an acute exacerbation of schizophrenia who had completed a 6-week double-blind study of lurasidone.Patients and Methods: A total of 289 adult patients with schizophrenia completed the double-blind study and enrolled in the 12-week extension study. Lurasidone was flexibly dosed at 40 or 80 mg/day. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) subscale scores, Clinical Global Impression-Severity Scale (CGI-S), and Calgary Depression Scale for Schizophrenia (CDSS), analyzed based on last observation carried forward (LOCF-endpoint). Safety/tolerability assessments included adverse events, body weight, laboratory tests, and discontinuation due to adverse events.Results: Mean endpoint change was greater for lurasidone in modal doses of 80 mg/d (N=136) vs 40 mg/d (N=153) on the PANSS positive subscale (− 3.0 vs − 2.3), PANSS negative subscale (− 1.9 vs − 1.7), PANSS General Psychopathology subscale (− 5.1 vs − 3.8), the CGI-S score (− 0.5 vs − 0.4), and the CDSS score (− 0.7 vs − 0.1). Discontinuation rates due to adverse events on lurasidone modal 80 mg/d vs

Masaomi Iyo,1 Jun Ishigooka,2 Masatoshi Nakamura,3 Reiko Sakaguchi,4 Keisuke Okamoto,5 Yongcai Mao,6 Joyce Tsai,7 Alison Fitzgerald,8 Kentaro Takai,9 Teruhiko Higuchi10,11 1Department of Psychiatry, Graduate School of Medicine, Chiba University, Chiba, Japan; 2Institute of CNS Pharmacology, Tokyo, Japan; 3Department of Data Science, Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan; 4Department of Clinical Research, Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan; 5Department of Clinical Operation, Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan; 6Division of Data Science, Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA; 7Division of Clinical Research, Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA; 8Division of Clinical Operations, Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA; 9Medical Affairs, Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan; 10Japan Depression Center, Tokyo, Japan; 11National Center of Neurology and Psychiatry, Tokyo, JapanCorrespondence: Kentaro Takai Email kentaro-takai@ds-pharma.co.jpPurpose: The goal of this study was to evaluate the safety and effectiveness of lurasidone among patients with schizophrenia in a 12-week open-label extension study.Patients and Methods: Patients who completed a 6-week, double-blind, placebo-controlled study were enrolled in a 12-week open-label extension study with flexible dosing of lurasidone at 40 or 80 mg/day. Safety assessments included adverse events, vital signs, laboratory tests, and electrocardiogram (ECG) parameters. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression-Severity Scale (CGI-S), Calgary Depression Scale for Schizophrenia (CDSS) and quality of life measure.Results: A total of 289 patients were enrolled in the open-label extension study. Rates of treatment-emergent adverse events (TEAEs) were low; akathisia was the most common TEAE w