A large survey of nocturia related to sleep quality and daytime quality of life in a young Japanese population: NOCTURNE study.

AIMS: Nocturia, due to nocturnal polyuria and other conditions associated with nocturnal voiding, affects sleep quality and daytime quality of life (QOL). We aimed to investigate the relationship among nocturia, sleep quality, and daytime QOL in a young Japanese population. METHODS: This epidemiological study analyzed data from a retrospective data set containing sleep data from wearable devices worn by 9446 Japanese users and a prospective data set containing answers to a 10-item questionnaire completed by a subset of 605 users in the retrospective dataset. We recorded the first uninterrupted sleep period (FUSP), total sleep time (TST), number of nocturnal voids, sleep quality, daytime QOL, bothering nocturnal voids, and early wake-ups in the morning. RESULTS: The subjects were 18-65 years old. The mean TST was 6.7 ± 0.9 h, and the mean number of wake-ups was 2.11 ± 1.1. FUSP and TST decreased (from 334 ± 114 to 173 ± 74 min and 5.9 ± 1.0 to 5.5 ± 1.0 h, respectively) with an increasing number of nocturnal voids, and the change was statistically significant. Logistic regression analysis showed a statistically significant relationship between nocturia and FUSP and the number of wake-ups. CONCLUSION: Nocturia has close relationships with FUSP and the number of wake-ups and can result in decreased daytime QOL in young Japanese people.

Recombinant FIX Fc fusion protein activity assessment with the one-stage clotting assay: A multicenter, assessor-blinded, prospective study in Japan (J-Field Study).

INTRODUCTION: The one-stage clotting assay is used to measure factor IX (FIX) activity in patients' plasma samples and in FIX products for hemophilia treatment. However, the diversity of reagents and instruments has resulted in significant FIX assay variability. METHODS: The accuracy of the one-stage clotting assay to measure recombinant FIX Fc fusion protein (rFIXFc) activity was evaluated by major Japanese hemophilia treatment centers and commercial laboratories that measure factor IX activity for a majority of hemophilia B patients in Japan. Plasma-derived FIX (pdFIX) and recombinant FIX (rFIX) products were used as comparators. FIX-deficient plasma was spiked with four levels of FIX products based on label potency and measured under blinded conditions by routine one-stage clotting assay procedures in 19 participating laboratories. Interlaboratory coefficient of variation and spike recovery were calculated. RESULTS: Interlaboratory coefficient of variation of rFIXFc was not significantly different from that of rFIX, but appeared larger than that of pdFIX. Mean spike recovery for rFIXFc was generally comparable to rFIX and pdFIX. However, larger discrepancies between pdFIX and rFIX were observed in three of nine laboratories using ellagic acid-based activated partial thromboplastin time reagents. CONCLUSION: Recombinant FIX Fc fusion protein activity was found to be similar to that of rFIX or pdFIX by the one-stage clotting assay. However, minimizing interlaboratory variability is vital for optimizing future patient care.

Phosphoproteomic and proteomic profiling of serine/threonine protein kinase PkaE of Streptomyces coelicolor A3(2) and its role in secondary metabolism and morphogenesis.

This study aimed to investigate the role of serine/threonine kinase PkaE in Streptomyces coelicolor A3(2). Liquid chromatography tandem mass spectrometry was performed for comparative phosphoproteome and proteome analyses of S. coelicolor A3(2), followed by an in vitro phosphorylation assay. Actinorhodin production in the pkaE deletion mutant was lower than that in wild-type S. coelicolor A3(2), and the spores of the pkaE deletion mutant were damaged. Furthermore, phosphoproteome analysis revealed that 6 proteins were significantly differentially hypophosphorylated in pkaE deletion mutant (p < 0.05, fold-change ≤ 0.66), including BldG and FtsZ. In addition, the in vitro phosphorylation assay revealed that PkaE phosphorylated FtsZ. Comparative proteome analysis revealed 362 differentially expressed proteins (p < 0.05) and six downregulated proteins in the pkaE deletion mutant involved in actinorhodin biosynthesis. Gene ontology enrichment analysis revealed that PkaE participates in various biological and cellular processes. Hence, S. coelicolor PkaE participates in actinorhodin biosynthesis and morphogenesis.

Long-term efficacy and safety of intramuscular interferon beta-1a: Randomized postmarketing trial of two dosing regimens in Japanese patients with relapsing-remitting multiple sclerosis.

OBJECTIVES: To evaluate the efficacy and safety of 2 years of treatment with intramuscular interferon beta-1a (IM IFN beta-1a) in Japanese patients with relapsing-remitting multiple sclerosis, with an exploratory analysis of the impact of initial dose titration on tolerability. METHODS: Japanese patients with relapsing-remitting multiple sclerosis were randomized to receive IM IFN beta-1a at dosages of either 30mcg once weekly (full-dose group, n=50) or 15mcg once weekly for 2 weeks then 30mcg once weekly thereafter (titration group, n=50). Key outcomes included annualized relapse rate (ARR) at 2 years (primary endpoint), change in disability measured using the Expanded Disability Status Scale (EDSS), safety, and tolerability. RESULTS: The ARR (95% CI) decreased from 1.540 (1.381-1.718) at baseline to 0.371 (0.240-0.571) at Year 1 and 0.351 (0.244-0.503) at Year 2. EDSS improvements were apparent from Week 24; the mean change from baseline EDSS score (2.1) at Year 2 was -0.34 (P=0.004). The most frequently reported adverse events were influenza-like illness (92%), nasopharyngitis (57%), relapse of multiple sclerosis (51%), and injection-site reaction (30%). The overall incidence and severity of influenza-like symptoms were similar in the full-dose group and titration group; only 1 participant, in the full-dose group (2%), experienced severe influenza-like symptoms. However, the incidence of influenza-like symptoms was slightly reduced at earlier timepoints in the titration group. CONCLUSIONS: The results of this 2-year study demonstrate that IM IFN beta-1a can be used effectively and safely in Japanese patients with relapsing-remitting multiple sclerosis for an extended period of time.