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Seiko Miyata,1,* Kunihiro Iwamoto,1,* Ippei Okada,1,* Akihiro Fujimoto,2 Yuki Kogo,2 Daisuke Mori,1,3,4 Manabu Amano,5 Nao Matsuyama,5 Kazuki Nishida,5 Masahiko Ando,5 Toshiaki Taoka,6 Shinji Naganawa,7 Norio Ozaki1,4 1Department of Psychiatry, Nagoya University, Graduate School of Medicine, Nagoya, Japan; 2Medical Headquarters, Eisai Co., Ltd., Tokyo, Japan; 3Brain and Mind Research Center, Nagoya University, Nagoya, Japan; 4Pathophysiology of Mental Disorders, Nagoya University, Graduate School of Medicine, Nagoya, Japan; 5Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan; 6Department of Innovative Biomedical Visualization (Ibmv), Nagoya University, Graduate School of Medicine, Nagoya, Japan; 7Department of Radiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan*These authors contributed equally to this workCorrespondence: Seiko Miyata, Department of Psychiatry, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan, Tel +81 52 744 2282, Fax +81 52 744 2293, Email miyata.seiko.v4@f.mail.nagoya-u.ac.jpPurpose: Both subjective and objective evaluations are essential for the treatment of insomnia. Lemborexant has been shown to be effective in the long-term based solely on a subjective basis, and no long-term objective measures have been evaluated under natural sleep conditions. Small, lightweight sleep electroencephalogram (EEG) monitor was used, instead of polysomnography, to objectively evaluate sleep at home 4 and 12 weeks after lemborexant treatment.Patients and Methods: Adults and elderly subjects with insomnia disorder, per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were enrolled in this open-label, single-arm, single-center trial. Objective and subjective measures of sleep were prospectively assessed. Sleep disturbance, excessive sleepiness, and depressive symptoms were assessed using questionnaires.Results: A total of 45 subjects were screened, of which 33 were enrolled. Paired t-tests were conducted to evaluate changes in sleep variables and compared with the baseline; subjects showed significant improvements in objective sleep efficiency (SE) and subjective sleep parameters at weeks 4 and 12 following treatment with lemborexant. When baseline values were taken into account, a repeated-multivariate analysis of variance (MANOVA) revealed statistically significant changes in the objective measures. Sleep disturbance, excessive sleepiness, and depressive symptoms improved after three months of lemborexant treatment.Conclusion: Furthermore, lemborexant therapy improved nocturnal sleep, when measured objectively using sleep EEG monitoring at home, and improved daytime sleepiness and depressive symptoms in older adults with insomnia disorder.Keywords: insomnia, lemborexant, objective sleep evaluation, portable sleep EEG monitoring, subjective sleep evaluation

Masaya Ogasawara,1 Masahiro Takeshima,1 Shumpei Kosaka,2 Aya Imanishi,1 Yu Itoh,1 Dai Fujiwara,1 Kazuhisa Yoshizawa,1 Norio Ozaki,3 Kazuyuki Nakagome,4 Kazuo Mishima1 1Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan; 2Department of Psychiatry, Akita Prefectural Center for Rehabilitation and Psychiatric Medicine, Daisen, Japan; 3Department of Pathophysiology of Mental Disorders, Nagoya University Graduate School of Medicine, Nagoya, Japan; 4Department of Psychiatry, National Center of Neurology and Psychiatry, Tokyo, JapanCorrespondence: Kazuo Mishima, Department of Neuropsychiatry, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan, Tel +81-18-884-6122, Fax +81-18-884-6445, Email clocksclub@gmail.comPurpose: Sleep-tracking devices have performed well in recent studies that evaluated their use in healthy adults by comparing them with the gold standard sleep assessment technique, polysomnography (PSG). These devices have not been validated for use in patients with psychiatric disorders. Therefore, we tested the performance of three sleep-tracking devices against PSG in patients with psychiatric disorders.Patients and methods: In total, 52 patients (32 women; 48.1 ± 17.2 years, mean ± SD; 18 patients diagnosed with schizophrenia, 19 with depressive disorder, 3 with bipolar disorder, and 12 with sleep disorder cases) were tested in a sleep laboratory with PSG, along with portable electroencephalography (EEG) device (Sleepgraph), actigraphy (MTN-220/221) and consumer sleep-tracking device (Fitbit Sense).Results: Epoch-by-epoch sensitivity (for sleep) and specificity (for wake), respectively, were as follows: Sleepgraph (0.95, 0.76), Fitbit Sense (0.95, 0.45) and MTN-220/221 (0.93, 0.40). Portable EEG (Sleepgraph) had the best sleep stage-tracking performance. Sleep-wake summary metrics demonstrated lower performance on poor sleep (ice, shorter total sleep time, lower sleep efficiency, longer sleep latency, longer wake after sleep onset).Conclusion: Devices demonstrated similar sleep-wake detecting performance as compared with previous studies that evaluated sleep in healthy adults. Consumer sleep device may exhibit poor sleep stage-tracking performance in patients with psychiatric disorders due to factors that affect the sleep determination algorithm, such as changes in autonomic nervous system activity. However, Sleepgraph, a portable EEG device, demonstrated higher performance in mental disorders than the Fitbit Sense and actigraphy.Keywords: polysomnography, actigraphy, portable EEG, consumer sleep technologies, psychiatric patients

Keita Kawai,1 Kunihiro Iwamoto,1 Seiko Miyata,1 Ippei Okada,1 Motoo Ando,1 Hiroshige Fujishiro,1 Akiko Noda,2 Norio Ozaki1 1Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan; 2Department of Biomedical Sciences, Chubu University Graduate School of Life and Health Sciences, Kasugai, JapanCorrespondence: Kunihiro Iwamoto, Department of Psychiatry, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan, Tel +81-52-744-2282, Fax +81-52-744-2293, Email iwamoto@med.nagoya-u.ac.jpPurpose: Sleep state misperception, which is the discrepancy between subjective and objective sleep, is often observed in patients with depression. This phenomenon may delay the remission of depression. Previous studies have focused on the total sleep time (TST) misperception, with many of these studies using actigraphy. Thus, our study investigated depressed patients with the exploratory aim of clarifying factors associated with the sleep state misperception including the wake after sleep onset (WASO) misperception, with their objective sleep additionally evaluated by polysomnography (PSG).Patients and Methods: We conducted a cross-sectional study. Before undergoing overnight PSG monitoring, 40 patients with depression completed questionnaires that included the Beck Depression Inventory (BDI), Epworth sleepiness scale, Temperament and Character Inventory, and the Pittsburgh sleep quality index. Patients were also asked to estimate their subjective sleep duration after they woke up in the morning. Based on this data, we calculated the misperception using the following formula: subjective sleep duration minus objective sleep duration. We compared each factor between negative and positive misperception groups and the multiple regression analysis was performed for TST and WASO misperception, respectively.Results: Although sleep architectures, age, severity of depression and obstructive sleep apnea (OSA) exhibited differences in underestimating or overestimating the WASO, only sex differences were associated with underestimating or overestimating their total sleep time (TST). Moreover, BDI, the severity of OSA, sleep architectures (N1% and N2%), and benzodiazepine (BZD) use were significantly correlated with WASO misperception, whereas only OSA severity was significantly correlated with TST misperception. A subsequent multiple regression analysis demonstrated the BDI was independently correlated with the WASO misperception (β=0.341, p=0.049).Conclusion: In clinical practice, interventions especially for OSA, and the reduction of depressive symptoms are an important method for improving patient sleep perception. Moreover, current results suggest that BZD prescriptions should be avoided as well.Keywords: insomnia, personality, sleep architectures, discrepancy, sleep disorders

Takayoshi Ueno,1 Kazuhira Endo,1 Kiyomi Hori,2 Noriyuki Ozaki,2 Akira Tsuji,1 Satoru Kondo,1 Naohiro Wakisaka,1 Shigeyuki Murono,1 Kazunori Kataoka,3,4 Yasuki Kato,5 Tomokazu Yoshizaki11Division of Otolaryngology-Head and Neck Surgery, 2Department of Functional Anatomy, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan; 3Department of Materials Engineering, Graduate School of Engineering, 4Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 5Research Division, NanoCarrier Co., Ltd, Chiba, JapanAbstract: Oxaliplatin, a third-generation platinum compound incorporating oxalate and 1,2-diaminocyclohexane platinum, has been widely used in chemotherapy regimens for the treatment of metastatic colorectal cancer. Because of its wide spectrum of antitumor activity, oxaliplatin has been applied for the treatment of other carcinomas. However, the antitumor activity of single-agent oxaliplatin is insufficient. To increase its antitumor effects, polymeric micellar nanoparticles incorporating 1,2-diaminocyclohexane platinum (NC-4016) have been developed. The present study was designed to evaluate the efficacy of NC-4016 and its association with peripheral neuropathy, which is a primary dose-limiting factor in oxaliplatin therapy. The in vitro antitumor activity of NC-4016 was investigated using human carcinoma cell lines. To investigate the antitumor effects of NC-4016 in vivo, nude mice bearing the human carcinoma cell line KB were administered NC-4016 or oxaliplatin. The in vitro growth-inhibiting effect of NC-4016 was significantly weaker than that of oxaliplatin. However, the antitumor efficacy of NC-4016 was superior to that of oxaliplatin in vivo. Moreover, we compared the severity of peripheral neuropathy induced by oxaliplatin and NC-4016 in a rat model. ­Oxaliplatin, NC-4016, or 5% glucose (control) were administered by a single tail vein injection. In the oxaliplatin-treated rats, neither mechanical nor heat allodynia was observed during the experimental period, whereas cold hyperalgesia/allodynia was observed from day 1 to 7. Conversely, cold hyperalgesia/allodynia was not observed in the NC-4016-treated rats. The present study demonstrated that the antitumor efficacy of NC-4016 was superior to that of oxaliplatin in a mouse model of human carcinoma cell line KB. In addition, NC-4016-treated rats did not develop acute cold hypersensitivity, which is frequently experienced by patients after oxaliplatin administration.Keywords: oxaliplatin, carcinoma, chemotherapy, drug delivery system

We present the chemical bonding and electronic properties of liquid methane at temperatures from 2000 to 4000 K and high densities of up to 3.0 g/cm3, calculated using ab initio molecular dynamics simulations in combination with the Mulliken population analysis. Bond-overlap populations and pair distribution functions are studied to investigate the evolution of electron delocalization accompanying atomic structure change as the density is increased. In addition, we also investigated the bandgap energy, electronic density of states, and spatial distribution of electron density. We observed that molecular hydrogen and C‒C bonds are formed after methane dissociates, and then the system undergoes a nonmetal–metal transition coinciding with hydrogen being transformed from the molecular to the atomic state. The C‒C bonds in the system retain covalent character, even at the highest density of 3.0 g/cm3. [ABSTRACT FROM AUTHOR]

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

When a laser is focused on an underwater object, it experiences a large amount of pressure owing to the plasma confinement effect of water. A hemispherical bubble is generated on the surface of the object, and large pressure is generated when the bubble collapses. In this study, we conducted experiments using different laser energies to analyze the pressure–time histories associated with bubble contraction. The maximum pressure was 10%–40% of the laser ablation pressure, whereas the pressure pulse width was 5–10 times longer than the laser pulse width. Furthermore, the bubble motion could be adiabatically explained, except for the plasma interaction region. The results indicate that the pressure at which the bubble collapses does not depend on the maximum size of the generated bubble but depends on the energy of water vapor within the bubble. [ABSTRACT FROM AUTHOR]

Ultrahigh-energy density (UHED) states greater than 1 Gbar pressure are typically observed under extreme conditions, such as in the core of an inertial confinement fusion implosion. A novel alternative approach for generating volumetric UHED states is to use nanowire arrays irradiated with a femtosecond ultrahigh-intensity laser. In this paper, we present an experimental investigation on laser absorption and energy transport in nanowire arrays irradiated with a picosecond kilojoule petawatt laser. The laser–target interactions were studied by measuring the x-ray emission and escaping hot electrons from a bare Cu foil and a foil with a nanowire array grown on its surface. The measured Cu-Kα and He-α emissions from the nanowire array were higher than those from the flat foil. In addition, hot electrons observed from the front surface of the nanowire array were enhanced. On the other hand, despite the stronger Kα emission from the nanowire array and the enhancement of hot electrons escaping from the front surface of the nanowire array, the number of hot electrons observed from the rear side of the flat foil target was slightly lower than that of the flat foil. A comparison of the experimental results with the results of a two-dimensional particle-in-cell simulation code suggested that the magnetic fields generated around the periodic nanowire array trap hot electrons, improving the electron-to-target energy coupling and efficiently producing UHED states. [ABSTRACT FROM AUTHOR]