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Summary: The association between nightmare frequency (NMF) and suicidal ideation (SI) is well known, yet the impact of the COVID‐19 pandemic on this relation is inconsistent. This study aimed to investigate changes in NMF, SI, and their association during the COVID‐19 pandemic. Data were collected in 16 countries using a harmonised questionnaire. The sample included 9328 individuals (4848 women; age M[SD] = 46.85 [17.75] years), and 17.60% reported previous COVID‐19. Overall, SI was significantly 2% lower during the pandemic vs. before, and this was consistent across genders and ages. Most countries/regions demonstrated decreases in SI during this pandemic, with Austria (−9.57%), Sweden (−6.18%), and Bulgaria (−5.14%) exhibiting significant declines in SI, but Italy (1.45%) and Portugal (2.45%) demonstrated non‐significant increases. Suicidal ideation was more common in participants with long‐COVID (21.10%) vs. short‐COVID (12.40%), though SI did not vary by COVID‐19 history. Nightmare frequency increased by 4.50% during the pandemic and was significantly higher in those with previous COVID‐19 (14.50% vs. 10.70%), during infection (23.00% vs. 8.10%), and in those with long‐COVID (18.00% vs. 8.50%). The relation between NMF and SI was not significantly stronger during the pandemic than prior (rs = 0.18 vs. 0.14; z = 2.80). Frequent nightmares during the pandemic increased the likelihood of reporting SI (OR = 1.57, 95% CI 1.20–2.05), while frequent dream recall during the pandemic served a protective effect (OR = 0.74, 95% CI 0.59–0.94). These findings have important implications for identifying those at risk of suicide and may offer a potential pathway for suicide prevention. [ABSTRACT FROM AUTHOR]

Summary: Many people report suffering from post‐acute sequelae of COVID‐19 or "long‐COVID", but there are still open questions on what actually constitutes long‐COVID and how prevalent it is. The current definition of post‐acute sequelae of COVID‐19 is based on voting using the Delphi‐method by the WHO post‐COVID‐19 working group. It emphasizes long‐lasting fatigue, shortness of breath and cognitive dysfunction as the core symptoms of post‐acute sequelae of COVID‐19. In this international survey study consisting of 13,628 subjects aged 18–99 years from 16 countries of Asia, Europe, North America and South America (May–Dec 2021), we show that post‐acute sequelae of COVID‐19 symptoms were more prevalent amongst the more severe COVID‐19 cases, i.e. those requiring hospitalisation for COVID‐19. We also found that long‐lasting sleep symptoms are at the core of post‐acute sequelae of COVID‐19 and associate with the COVID‐19 severity when COVID‐19 cases are compared with COVID‐negative cases. Specifically, fatigue (61.3%), insomnia symptoms (49.6%) and excessive daytime sleepiness (35.8%) were highly prevalent amongst respondents reporting long‐lasting symptoms after hospitalisation for COVID‐19. Understanding the importance of sleep‐related symptoms in post‐acute sequelae of COVID‐19 has a clinical relevance when diagnosing and treating long‐COVID. [ABSTRACT FROM AUTHOR]

Summary: There has been increasing concern about the long‐term impact of coronavirus disease 2019 (COVID‐19) as evidenced by anecdotal case reports of acute‐onset parkinsonism and the polysomnographic feature of increased rapid eye movement sleep electromyographic activity. This study aimed to determine the prevalence and correlates of dream‐enactment behaviours, a hallmark of rapid eye movement sleep behaviour disorder, which is a prodrome of α‐synucleinopathy. This online survey was conducted between May and August 2020 in 15 countries/regions targeting adult participants (aged ≥18 years) from the general population with a harmonised structured questionnaire on sleep patterns and disorders, COVID‐19 diagnosis and symptoms. We assessed dream‐enactment behaviours using the Rapid Eye Movement Sleep Behaviour Disorder Single‐Question Screen with an additional question on their frequency. Among 26,539 respondents, 21,870 (82.2%) answered all items that were analysed in this study (mean [SD] age 41.6 [15.8] years; female sex 65.5%). The weighted prevalence of lifetime and weekly dream‐enactment behaviours was 19.4% and 3.1% and were found to be 1.8‐ and 2.9‐times higher in COVID‐19‐positive cases, respectively. Both lifetime and weekly dream‐enactment behaviours were associated with young age, male sex, smoking, alcohol consumption, higher physical activity level, nightmares, COVID‐19 diagnosis, olfactory impairment, obstructive sleep apnea symptoms, mood, and post‐traumatic stress disorder features. Among COVID‐19‐positive cases, weekly dream‐enactment behaviours were positively associated with the severity of COVID‐19. Dream‐enactment behaviours are common among the general population during the COVID‐19 pandemic and further increase among patients with COVID‐19. Further studies are needed to investigate the potential neurodegenerative effect of COVID‐19. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to develop a Japanese version of the Hyperarousal Scale (HAS-J) and investigate its factor structure, reliability, and validity, as well as to calculate a cutoff score for the HAS-J and assess different levels of hyperarousal in insomnia patients and community dwellers. Methods: We recruited 224 outpatients receiving insomnia treatment (56.3% women; mean age 51.7 ± 15.6 years) and 303 community dwellers aged 20 years or older (57.8% women; mean age 43.9 ± 15.2 years). Exploratory and confirmatory factor analysis was performed to examine the factor structure of the HAS-J. Cronbach's α and McDonald's ω were then used to test internal consistency. To examine the scale's validity, we determined correlations between the HAS-J and other indexes and compared HAS-J scores between insomnia patients and community dwellers. We also compared HAS-J scores between two community-dweller groups (normal and poor sleepers) and two insomnia patient groups (with and without alleviation after treatment). Results: Following exploratory and confirmatory factor analysis, a 20-item measure emerged comprising three factors: "Introspectiveness and Reactivity," "Neuroticism," and "Insomnia." Confirmatory factor analysis showed a generally good fit for the model of the three-factor structure suggested by the exploratory factor analysis loadings (χ2 (163) = 327.423, (p < 0.001), CFI = 0.914, GFI = 0.872, AGFI = 0.835, RMSEA = 0.067). In insomnia patients, internal consistency indicated sufficient reliability of the HAS-J. Correlation analysis showed weak to moderate positive correlations of the HAS-J score with other indexes, indicating concurrent validity of the HAS-J. All HAS-J subscale scores were significantly higher in insomnia patients than in community dwellers. Additionally, the total score in patients with alleviation of insomnia was comparable to that in poor sleepers and significantly higher than that in normal sleepers. Conclusions: This study demonstrated the reliability and validity of the HAS-J, indicating that it is useful as a clinical scale of hyperarousal. The high level of hyperarousal in insomnia patients who were assessed to be in remission by the Insomnia Severity Index suggests a risk of insomnia recurrence in these patients. [ABSTRACT FROM AUTHOR]

Objectives: To develop a classification system for urine cytology with artificial intelligence (AI) using a convolutional neural network algorithm that classifies urine cell images as negative (benign) or positive (atypical or malignant). Patients and Methods: We collected 195 urine cytology slides from consecutive patients with a histologically confirmed diagnosis of urothelial cancer (between January 2016 and December 2017). Two certified cytotechnologists independently evaluated and labelled each slide; 4637 cell images with concordant diagnoses were selected, including 3128 benign cells (negative), 398 atypical cells, and 1111 cells that were malignant or suspicious for malignancy (positive). This pathologically confirmed labelled dataset was used to represent the ground truth for AI training/validation/testing. Customized CutMix (CircleCut) and Refined Data Augmentation were used for image processing. The model architecture included EfficientNet B6 and Arcface. We used 80% of the data for training and validation (4:1 ratio) and 20% for testing. Model performance was evaluated with fivefold cross‐validation. A receiver‐operating characteristic (ROC) analysis was used to evaluate the binary classification model. Bayesian posterior probabilities for the AI performance measure (Y) and cytotechnologist performance measure (X) were compared. Results: The area under the ROC curve was 0.99 (95% confidence interval [CI] 0.98–0.99), the highest accuracy was 95% (95% CI 94–97), sensitivity was 97% (95% CI 95–99), and specificity was 95% (95% CI 93–97). The accuracy of AI surpassed the highest level of cytotechnologists for the binary classification [Pr(Y > X) = 0.95]. AI achieved >90% accuracy for all cell subtypes. In the subgroup analysis based on the clinicopathological characteristics of patients who provided the test cells, the accuracy of AI ranged between 89% and 97%. Conclusion: Our novel AI classification system for urine cytology successfully classified all cell subtypes with an accuracy of higher than 90%, and achieved diagnostic accuracy of malignancy superior to the highest level achieved by cytotechnologists. [ABSTRACT FROM AUTHOR]

Summary: This protocol paper describes the second survey produced by the International Covid Sleep Study (ICOSS) group with the aim to examine the associations between SARS‐CoV‐2 infection and sleep, sleepiness, and circadian problems as potential predisposing factors for more severe COVID‐19 disease profile and for development of Long‐COVID in the general population. The survey consists of 47 questions on sleep, daytime sleepiness, circadian rhythm, health, mental wellbeing, life habits, and socioeconomic situation before and during the pandemic, and conditional questions to those reporting having had coronavirus infection, being vaccinated, or suffering from particular sleep symptoms or sleep disorders. Surveys will be administered online between May and November 2021 in Austria, Brazil, Bulgaria, Canada, China, Croatia, Finland, France, Germany, Israel, Italy, Japan, Norway, Portugal, Sweden and USA. Data collected by the survey will give valuable information on the open questions regarding COVID‐19 disease risk factors, symptomatology and evolution of Long‐COVID, and on other long‐term consequences related to the pandemic. [ABSTRACT FROM AUTHOR]

Social restrictions during the coronavirus disease (COVID-19) pandemic have impacted sleep behavior and sleep problems, and their related daytime functioning in young adults. However, no studies have examined such changes in young individuals from countries with mild infection intensity and social restrictions. Therefore, we focused on sleep behaviors and sleep issues in young people in Japan. This study was conducted before and after the pandemic (October 2019 and May 2020, respectively). In total, 2,222 (1,371 students and 851 workers) individuals participated and completed anonymous Web-based questionnaires concerning demographic characteristics, sleep behaviors, sleep problems using the Japanese version of the Epworth Sleepiness Scale (JESS) and the Athens Insomnia Scale (AIS-J), psychological distress using the Japanese version of the Kessler Psychological Distress Scale, and health-related quality of life (HRQoL) evaluated with the Short Form-8 (SF-8). A significantly delayed sleep phase was observed in the second survey compared to the first (p <.001) and was more pronounced in students than in workers (p <.001). The total sleep time, social jetlag degree, and JESS, AIS-J, and SF-8 scores were significantly improved after the pandemic (p <.001, p <.001, p <.001, p <.001, p <.05, and p <.001, respectively). Careful monitoring of whether these modest changes can lead to adjustment concerns is needed. [ABSTRACT FROM AUTHOR]

Background: Delayed sleep-wake phase disorder (DSWPD) is more prevalent among the younger generation. However, the prevalence of this disorder in Asia, particularly Japan, has not yet been elucidated. Furthermore, the impact of DSWPD morbidity on daytime functioning and factors associated with the presence of the disorder remain unclear. Methods: A web-based survey was conducted among youth aged 15–30 years. In total, 7,810 individuals completed the questionnaire. The questionnaire included items on sociodemographic variables as well as the Japanese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry self-report (J-BRIAN-SR), which assesses the risk of DSWPD, sleep behaviors and possibly related lifestyle variables, productivity loss [WHO Health and Work Performance Questionnaire (HPQ)], and health-related quality of life (HRQOL). The risk of DSWPD was indicated by a J-BRIAN-SR score greater than or equal to 40 points and days of absence ≥4 days per month. After comparing these variables for participants at risk of DSWPD and those who were not, the factors associated with the risk of DSWPD were examined using logistic regression analysis, with sociodemographic and lifestyle variables as independent variables. Results: The overall prevalence of participants at risk DSWPDs was 4.3%. Compared with participants without DSWPD, those at risk of DSWPD presented significantly worse HPQ and HRQOL scores. The risk of DSWPD was positively associated with the presence of currently treated diseases, length of nighttime liquid crystal display (LCD) viewing, and being a high school/university students. It was negatively associated with habitual exercise. Conclusion: The risk of DSWPD seemed to be consistent with reports from Western countries, and individuals possibly affected by the disorder were thought to have deteriorated daytime functioning. In addition, lifestyle specific to youth, such as long-term LCD viewing at night and relatively loose social constraints, could be associated with the presence of DSWPD in this generation. [ABSTRACT FROM AUTHOR]

Social jetlag, a form of circadian misalignment, has been suggested to induce several clinical symptoms such as mental/physical health problems. However, evidence on the association of social jetlag with general daytime functioning (e.g., school life) is limited. This cross-sectional study aimed to 1) estimate the distribution of social jetlag exceeding one hour and 2) comprehensively explore the associations between social jetlag and irritable mood, daytime sleepiness, and poor academic performance among Japanese adolescents. The study included 4,782 students aged 12–15 years, from 13 junior high schools, who completed a self-administered questionnaire. Social jetlag was calculated as the difference in the midpoint of sleep between weekdays and weekends and was categorized as follow: negative, <1 h, 1–2 h, or ≥2 h. Outcomes were irritable mood, daytime sleepiness, and academic performance, which were analyzed with generalized linear mixed models to examine the relations with social jetlag, with adjustments for potential confounders like sleep quality. The distribution of social jetlag of ≥1 h was 51.1%, including 1–2 h (35.8%) and ≥2 h (15.3%). Its most frequently observed duration was 0 to <1 h (41.0%), followed by negative social jetlag (7.9%). The full adjusted model revealed that social jetlag of ≥1 h was associated with elevated risk of irritable mood, daytime sleepiness, and poor academic performance, while negative social jetlag was associated only with poor academic performance. Social jetlag was highly prevalent among Japanese adolescents and could be a major risk factor for irritable mood, daytime sleepiness, and poor academic performance. Abbreviations: BMI, Body mass index; DLMO, Dim light melatonin onset; CIs, Confidence intervals; MSF, The midpoints of sleep on free days; MSFsc, Sleep-corrected MSF; MSW, The midpoints of sleep on weekdays; PDSS, The Pediatric Daytime Sleepiness Scale. [ABSTRACT FROM AUTHOR]

Background: The histamine H3 receptor has emerged as one of the most promising targets of novel pharmacotherapy for narcolepsy. Studies now aim to investigate the optimal dose of enerisant, a novel H3 antagonist/inverse agonist, for the treatment of excessive daytime sleepiness in patients with narcolepsy. Methods: We conducted two phase 2, fixed-dose, double-blind, randomized, placebo-controlled trials in patients with narcolepsy. The first phase 2 study (Study 1) was conducted to investigate the efficacy and safety of enerisant at dosages of 25, 50, and 100 mg/day administered for 3 weeks based on the results of a phase 1 study conducted on healthy volunteers. The primary endpoint was mean sleep latency in maintenance of wakefulness test (MWT), and the secondary endpoint was the total score on the Epworth Sleepiness Scale (ESS). The dosages of enerisant in the second phase 2 study (Study 2) were set at 5 and 10 mg/day based on the simulation of receptor occupancy results from positron emission tomography study. Results: Forty-six and fifty-three patients were randomized in Study 1 and Study 2, respectively. The efficacy of enerisant was partially confirmed in Study 1 with ESS; however, the doses were not tolerated, and there were many withdrawals due to adverse events (mainly insomnia, headache, and nausea). The doses in Study 2 were well tolerated, with a lower incidence of adverse events in Study 2 than in Study 1, although the efficacy could not be confirmed with MWT and ESS in Study 2. Conclusions: The optimal dose of enerisant could not be determined in these two studies. Although enerisant has a favorable pharmacokinetic profile, it is thought to have large interindividual variabilities in terms of efficacy and safety, suggesting the necessity of tailored dosage adjustments. Trial registration: ClinicalTrials.gov identifier: NCT03267303; Registered 30 August 2017 (Study 2). Japic identifier: JapicCTI-142529; Registered 7 May 2014 (Study 1) and JapicCTI-173689; Registered 30 August 2017, https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?clinicalTrialId=29277 (Study 2). [ABSTRACT FROM AUTHOR]

The prevalence of sleep-disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Since sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021. [ABSTRACT FROM AUTHOR]

Purpose: In 2-dimensional lateral cephalometric radiographs, patients with severe obstructive sleep apnea (OSA) exhibit a more crowded oropharynx in comparison with non-OSA. We tested the hypothesis that machine learning, an application of artificial intelligence (AI), could be used to detect patients with severe OSA based on 2-dimensional images. Methods: A deep convolutional neural network was developed (n = 1258; 90%) and tested (n = 131; 10%) using data from 1389 (100%) lateral cephalometric radiographs obtained from individuals diagnosed with severe OSA (n = 867; apnea hypopnea index > 30 events/h sleep) or non-OSA (n = 522; apnea hypopnea index < 5 events/h sleep) at a single center for sleep disorders. Three kinds of data sets were prepared by changing the area of interest using a single image: the original image without any modification (full image), an image containing a facial profile, upper airway, and craniofacial soft/hard tissues (main region), and an image containing part of the occipital region (head only). A radiologist also performed a conventional manual cephalometric analysis of the full image for comparison. Results: The sensitivity/specificity was 0.87/0.82 for full image, 0.88/0.75 for main region, 0.71/0.63 for head only, and 0.54/0.80 for the manual analysis. The area under the receiver-operating characteristic curve was the highest for main region 0.92, for full image 0.89, for head only 0.70, and for manual cephalometric analysis 0.75. Conclusions: A deep convolutional neural network identified individuals with severe OSA with high accuracy. Future research on this concept using AI and images can be further encouraged when discussing triage of OSA. [ABSTRACT FROM AUTHOR]

Summary: Recent evidence suggests that short‐term obstructive sleep apnea (OSA) treatment could affect OSA pathogenesis such as ventilatory control. The aim of our present study was to identify the impact of long‐term treatment on the change in pathogenesis and natural progression of OSA. In a longitudinal analysis of a non‐obese cohort study, patients with OSA treated with either continuous positive airway pressure (CPAP) or an oral appliance (OA), interrupted their treatment for 1 week and underwent a polysomnography (PSG) off treatment that was compared with their initial PSG taken 5 years before treatment initiation. In all, 154 consecutive patients with OSA who were treated by CPAP using an auto‐titrating continuous positive airway pressure device (CPAP‐APAP) (n = 112), or by OA (n = 27) or were untreated (n = 15), PSG was performed twice with a median (range) follow‐up of 93 (60–176) months. Multivariate logistic regression showed that reduction of body mass index (BMI) and good treatment adherence to be significant predictors of favourable OSA progression, as represented by an improved or unchanged apnea–hypopnea index (AHI) (odds ratios were 5.14 and 2.89, respectively). Amongst the patients with an unchanged BMI and good CPAP‐APAP adherence (n = 55), the improvement in AHI was significantly associated with the decrease in supine non‐rapid eye movement‐AHI and mixed apnoea index/apnoea index, which are generally recognised to be determinants of ventilator instability. These findings suggest that not only weight but also treatment adherence are determinants in the natural progression of OSA severity. [ABSTRACT FROM AUTHOR]

Background: Young adults are likely to have activities and go to bed late at night due to their age-dependent delayed endogenous circadian clock. The purpose of the present study was to clarify sleep–wake rhythm and its association with lifestyle, health-related quality of life, and academic performance among nursing students. Methods: Self-reported questionnaires were distributed to undergraduate nursing students at six universities in Japan. Sleep–wake rhythm was assessed using the morningness-eveningness questionnaire. A quantitative design using the generalized linear mixed effect model was utilized to identify the factors related to the evening type among female nursing students (n = 447). Results: About 18% of the participants were identified as the evening type. Evening type was associated with living alone, part-time job, and club activity. Sleep duration on weekdays was shorter, meal time duration was the shortest, and the percentages of students who skipped meals and those who gained body weight were higher in the evening type than in the morning type and intermediate type. Mental health-related quality of life was lower in the intermediate type and evening type than in the morning type, while there was no difference in physical health-related quality of life among these groups. The percentages of the nursing students who have experienced absence, tardiness, falling asleep during class, and/or interference with academic achievement were higher in the evening type than in other groups. Conclusions: The present study has important implications for nursing students' biological characteristics and lifestyle, which are associated with their health-related quality of life and academic performance. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the impact of sleep problems on job stress in office workers. Methods: This study included 4645 office workers from 29 companies who completed the study questionnaires between April 2017 and April 2019 in Japan. Sleep duration was assessed based on the participants' subjective sleep schedule on workdays and free days. The midpoint of sleep on free days (sleep‐corrected) and social jetlag were calculated in accordance with the Munich Chronotype Questionnaire. To assess job stress, we used the 57‐item Brief Job Stress Questionnaire. Results: Multivariate logistic regression analysis revealed that the following factors were significantly associated with high job stress in office workers: a sleep duration <6 h on workdays (OR = 1.77, 95% CI = 1.46–2.15, P < 0.001), a sleep duration <6 h on free days (OR = 1.40, 95% CI = 1.05–1.87, P = 0.022), a sleep duration of at least 8 h on free days (OR = 1.31, 95% CI = 1.06–1.60, P = 0.011), and more than 2 h of social jetlag (OR = 1.33, 95% CI = 1.04–1.70, P = 0.022). Conclusion: This study suggests that insufficient sleep, long sleep durations on free days, and social jetlag may be associated with high job stress in office workers. [ABSTRACT FROM AUTHOR]

Background: The situation of work productivity loss due to sleep disorders/problems among workers in industrialized societies remains unclear. The purpose of this study was to clarify the prevalence of insomnia symptoms and actual situation of work productivity by job type (white-collars/blue-collars) among construction/civil engineering workers in Japan and evaluate the association between insomnia symptoms and work productivity adjusting for sleep duration and sociodemographic, work-related, and health-related variables.Methods: This cross-sectional study included 17,828 construction/civil engineering workers (15,837 males and 1991 females) aged 40 to 74 years in Japan. The questionnaire consisted of socio-demographic characteristics, information on work productivity (work performance and absence), respective insomnia symptoms (difficulty initiating sleep; DIS, difficulty maintaining sleep; DMS, and early morning awakening; EMA), bedtime schedule, work-related factors (job type, working hours), and perceived health condition. To identify the associated factors of work productivity, the logistic regression analyses were conducted.Results: The percentages of workers who reported to be experiencing DIS, DMS, and EMA were 7.9, 16.3, and 13.1%, respectively. Poor work performance was associated with every insomnia symptom in both the blue-collar and white-collar workers. Meanwhile, absence was associated with DIS in blue-collar workers and both DIS and DMS in white-collar workers; however, not with EMA in both the groups. In blue-collar workers, engagement in shift work was associated with poor work performance.Conclusions: The present study revealed the association between insomnia symptoms and work productivity, suggesting the necessity of early prevention of insomnia among both blue-collar and white-collar workers. [ABSTRACT FROM AUTHOR]

We found that strawberry extract suppressed immunoglobulin (Ig) E production in vitro and in vivo, and identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as one of the IgE suppressor in the extract. We report here the effect of GAPDH on various Ig productions in vitro and in vivo. GAPDH suppressed IgE and enhanced IgA, IgG and IgM productions in ovalbumin (OVA)-stimulated human peripheral blood mononuclear cells. Oral administration of GAPDH at 10 mg/kg/day to OVA-induced allergy model mice tended to decrease total IgE level and increase total IgA and IgG levels in sera, and also decreased OVA-specific IgE and IgG levels. It is known that the increase of total IgA as well as the decrease of total and specific IgE is important for alleviating allergic symptoms. In addition, GAPDH accelerated IgA production and increased some cytokine secretions such as IL-4, TGF-β1 and IFN-γ in the OVA-immunized mice spleen lymphocytes. These cytokines involved in the class-switching, IgA enhancement, and IgE suppression, respectively, supporting above results. Our study suggests a possibility that oral administration of GAPDH may induce the immunomodulation in allergic responses. [ABSTRACT FROM AUTHOR]

Circadian clocks orchestrate multiple different physiological rhythms in a well-synchronized manner. However, how these separate rhythms are interconnected is not exactly understood. Here, we developed a method that allows for the real-time simultaneous measurement of locomotor activity and body temperature of mice using infrared video camera imaging. As expected from the literature, temporal profiles of body temperature and locomotor activity were positively correlated with each other. Basically, body temperatures were high when animals were in locomotion. However, interestingly, increases in body temperature were not always associated with the appearance of locomotor activity. Video imaging revealed that mice exhibit non-locomotor activities such as grooming and postural adjustments, which alone induce considerable elevation of body temperature. Noticeably, non-locomotor movements always preceded the initiation of locomotor activity. Nevertheless, non-locomotor movements were not always accompanied by locomotor movements, suggesting that non-locomotor movements provide a mechanism of thermoregulation independent of locomotor activity. In addition, in the current study, we also report the development of a machine learning-based recording method for the detection of circadian feeding and drinking behaviors of mice. Our data illustrate the potential utility of thermal video imaging in the investigation of different physiological rhythms. [ABSTRACT FROM AUTHOR]

Background: Although long-term use of benzodiazepines and benzodiazepine receptor agonists (BZDs) has been associated with an increased risk of dependence, the incidence, details of clinical manifestations, and triggering factors of withdrawal symptoms associated with long-term BZD use at common clinical doses remain unclear. Methods: In a multicenter, open-label study of 123 Japanese patients with insomnia, patients were given a common clinical dose of eszopiclone (2 mg) for 24 weeks, and then treatment was abruptly discontinued. Withdrawal symptoms were evaluated using the Benzodiazepine Hypnotics Withdrawal Symptom Scale (BHWSS). The Insomnia Severity Index (ISI) was used to rate insomnia severity during treatment and 2 weeks after discontinuation. Dependence and poor compliance during treatment without strict medication controls were evaluated with the Benzodiazepine Dependence Self Report Questionnaire short version (Bendep-SRQ SV) subscale sum scores for problematic use, preoccupation, and lack of compliance. Associations between the presence of clinically relevant withdrawal symptoms (BHWSS≥7) and demographic measures, ISI scores at Week 24, and Bendep-SRQ SV subscale sum scores were evaluated by multivariable stepwise logistic regression analyses. Results: Seventy-six patients completed treatment and 2 weeks of withdrawal; eight (10.5%) had clinically relevant withdrawal symptoms. On multiple logistic regression analysis, Bendep-SRQ SV subscale sum scores were correlated with withdrawal symptoms (odds ratio, 1.650; 95% confidence interval, 1.105–2.464; p = 0.014). Exacerbation of post-discontinuation insomnia was not significantly different between patients who showed clinically relevant withdrawal symptoms and those who did not (p = 0.245). Conclusions: Dependence and poor compliance may contribute to withdrawal symptoms with long-term BZD use. Providing guidance to ensure proper compliance is thought to be the best way to mitigate withdrawal symptoms. Trial registration: UMIN000024462 (18/10/2016). [ABSTRACT FROM AUTHOR]

Cataplexy is a sudden drop of antigravity-muscle tone triggered most often by positive emotional factors, which is one of the major symptoms of narcolepsy. Cataplexy has been treated pharmacologically, most often with tricyclic antidepressants. Even though tricyclic antidepressants are effective in reducing sleep paralysis and hypnagogic hallucinations, they even enhance daytime sleepiness, dizziness, and orthostatic hypotension. We assessed the anticataplectic effect of milnacipran, an SNRI, on human and canine narcolepsy. We also assessed the effect of milnacipran on REM sleep suppression in nocturnal sleep. Ten human patients with narcolepsy–cataplexy who changed medication from clomipramine to milnacipran due to side effects were enrolled. The change in the frequency of cataplexy and side effects before and after drug replacement was investigated. To assess milnacipran's depressant effect on REM sleep, we performed nocturnal polysomnography examinations twice on each eight healthy adult subjects who were administered with milnacipran or placebo. In the study on canine narcolepsy, four genetically narcoleptic Doberman pinschers were enrolled. The food-elicited cataplexy test was used to assess the anticataplectic effect of milnacipran. Milnacipran significantly reduced cataplexy from 9.3 to 5.5 episodes per month in human patients without much side effects. The percentage of REM sleep significantly decreased (p = 0.042) in the subjects with milnacipran (17.5 ± 1.7%) compared to subjects with placebo (21.5 ± 2.3%). Milnacipran also significantly reduced cataplexy dose-dependently in the study on canine narcolepsy. Milnacipran reduced cataplexy in human patients and REM sleep in healthy human subjects. Our study contributes further to previously reported role of adrenergic uptake inhibition in cataplexy. This compound had less side effect than those of tricyclic antidepressant, clomipramine. [ABSTRACT FROM AUTHOR]

Aims: Benzodiazepine receptor agonists (BZ‐RAs) are frequently prescribed to treat insomnia; however, their long‐term use is not recommended. To introduce an appropriate pharmaco‐therapy, the current state and background factors of BZ‐RAs' dependence must be elucidated. In this study, we developed a Japanese version of the Benzodiazepine Dependence Self‐Report Questionnaire (Bendep‐SRQ‐J) and conducted a study of BZ‐RAs' use disorder. Methods: The Bendep‐SRQ‐J was created with permission from the original developer. Subjects were inpatients and outpatients receiving BZ‐RAs between 2012 and 2013. Clinical data collected were Bendep‐SRQ‐J scores, sleep disorders for which BZ‐RAs were prescribed, physical comorbidities, psychotropic drugs, and lifestyle factors. Logistic analysis was performed to extract factors associated with severe symptoms. Results: Of the 707 patients prescribed BZ‐RAs, 324 had voluntarily tapered or discontinued their drugs. Logistic analysis showed that the total number of drugs administered in the last 6 months correlated with both worsening of symptoms or conditions. This was more notable among younger patients, and the proportion of patients with severe symptoms or conditions increased with the increasing number of drugs. Conclusion: Using the Bendep‐SRQ‐J, we elucidated the current state of BZ‐RA dependence. Nearly half of the patients were non‐compliant. The proportion of patients with severe symptoms or disease conditions increased with the increase in the number of drugs administered. These findings highlight the need for clinicians to be aware of the likelihood of benzodiazepine dependence, especially in young patients and patients prescribed multiple hypnotics. [ABSTRACT FROM AUTHOR]

Background: Although earlier studies have demonstrated that circadian rhythm sleep-wake disorders (CRSWD) are more prevalent in visually impaired individuals, the actual prevalence of CRSWD and insomnia among the visually impaired Japanese population remains unclear. The aim of this cross-sectional, telephone-based study was to estimate the prevalence of CRSWD and insomnia, and explore factors associated with CRSWD and insomnia among visually impaired Japanese individuals.Methods: A nationwide telephone survey was conducted among visually-impaired individuals through local branches of the Japan Federation of the Blind. In total, 157 visually impaired individuals were eligible for this study. Demographic information and information about visual impairments, lifestyle, and sleep patterns were assessed using questionnaires and subsequent telephone interviews. CRSWD and insomnia were defined according to the International Classification of Sleep Disorders-Third Edition criteria.Results: The prevalence of CRSWD in visually impaired individuals was 33.1%. Among those with CRSWD, a non-24-h/irregular sleep-wake rhythm type was the most frequently observed (26.8%), followed by an advanced sleep-wake phase type and a delayed sleep-wake phase type (3.8 and 2.5%, respectively). Furthermore, 28.7% of the visually impaired individuals were found to have insomnia. In the visually impaired individuals, the absence of light perception, unemployment, living alone, and use of hypnotics were significantly associated with CRSWD, whereas only the use of hypnotics was extracted as a marginally associated factor of insomnia.Conclusions: CRSWD and insomnia were highly prevalent in visually impaired Japanese individuals. The presence of CRSWD among the visually impaired individuals was associated with a lack of light perception and/or social zeitgebers. [ABSTRACT FROM AUTHOR]

Purpose: The upper airway (UA) anatomical collapsibility, UA muscle responsiveness, breathing control, and/or arousability are important contributing factors for obstructive sleep apnea (OSA). Differences in clinical manifestations of OSA are believed to reflect interactions among these factors. We aimed to classify OSA patients into subgroups based on polysomnographic (PSG) variables using cluster analysis and assess each subgroup's characteristics. Methods: Men with moderate or severe OSA and without any concomitant heart or psychosomatic disease were recruited. A hierarchical cluster analysis was performed using variables including fraction of apnea, respiratory event duration, minimum oxygen saturation, arousal rate before termination, and frequency of respiratory events in the supine position. The impact of sleep stages or body position on PSG variables was also evaluated in each cluster. Results: A total of 210 men (mean age, 50.0 years, mean body mass index, 27.4 kg/m2) were studied. The three subgroups that emerged from the analysis were defined as follows: cluster 1 (high fraction of apnea and severe desaturation (20%)), cluster 2 (high fraction of apnea and long event duration (31%)), and cluster 3 (low fraction of apnea (49%)). There were differences in the body mass index and apnea type between the three clusters. Sleep stages and/or body position affected PSG variables in each cluster. Conclusions: Patients with OSA could be divided into three distinct subgroups based on PSG variables. This clustering may be used for assessing the pathophysiology of OSA to tailor individual treatment other than continuous positive airway pressure therapy. [ABSTRACT FROM AUTHOR]

Misalignment between an individual's circadian phase and his/her environment due to social imposition is called social jetlag (SJL). SJL has emerged as a public health concern, as it contributes to an unhealthy lifestyle and adverse health outcomes. This study aimed to elucidate the percentage of SJL in a large Japanese population using the Japanese version of the Munich ChronoType Questionnaire (MCTQ). A total of 10,000 participants responded to a web-based cross-sectional survey, and the final sample comprised 3708 participants (60.1% male; average age 45.1 [SD 13.4] years). SJL was measured by subtracting each participant's midpoint of sleep on workdays from their midpoint of sleep on free days. The average [SD] absolute SJL (SJLabs) value was 0.91 [0.89] hours, and the percentage of participants with SLJabs of more than 1 h was 40.1%. Our data also showed that SJLabs becomes progressively smaller with advancing age. A considerable number of participants of our Japanese population showed differences in sleep behavior between workdays and free days. Young people in particular commonly oversleep on free days to compensate for the sleep debt accumulated over the workweek because of their late chronotype. [ABSTRACT FROM AUTHOR]

Conventionally, the alignment layer like polyimide is necessary for Liquid Crystal (LC) initial alignment. In this study, we have developed a novel reactive monomer (RM) for self vertical alignment (SVA). Doping this SVA RM into LC, we become able to manufacture VA mode Liquid Crystal Display panel without alignment layer. This technology would bring many merits to LCD performance. Also, this technology is very good compatibility with the Polymer Sustained Alignment (PSA) technology, that is widely used for LCD TV application etc. We report our achievement, comparing PSA. [ABSTRACT FROM AUTHOR]

Clock genes that comprise the circadian clock system control various physiological functions. Delayed sleep-wake phase disorder (DSWPD) and night eating syndrome (NES) are characterized by delayed sleep and meal timing, respectively. We estimated that clock gene expression rhythms in DSWPD patients may be delayed in comparison with the healthy subjects due to delayed melatonin secretion rhythms, producing eveningness chronotype in these individuals. However, it was difficult to estimate which clock gene expression rhythms were delayed or not in NES patients, because previous studies revealed that melatonin secretion rhythm was a little delayed compared with healthy individuals and that chronotype of NES patients depended on the individuals. Therefore, we examined expression rhythms of clock genes such as Period3 (Per3), nuclear receptor subfamily 1, group D, member 1 (Nr1d1) and Nr1d2 in these patients. Further, we expected sleep and meal patterns in DSWPD and NES patients may be more diverse than patterns observed in healthy subjects, and thus analyzed relationships among clock gene expression rhythms, sleep quality, sleep midpoint time, and meal times. We enrolled healthy male participants along with DSWPD and NES male patients, and asked all participants to answer questionnaires and to keep diaries to record information on their sleep and meals. Further, we asked them to collect 5–10 beard follicle samples, 6 times every 4 h. We measured clock gene expression rhythms using total RNA extracted from beard follicle cells. Peak time of clock gene expression in the NES group showed more diversity than the other groups, and that in the DSWPD group was delayed compared with the control group. In addition, the peak time of clock gene expression was negatively correlated with sleep quality and positively correlated with meal time after a long fast. Amplitudes of clock gene expression, especially Per3, positively responded to better mental and physical conditions as well as with better sleep quality. Results of this study suggest that peak times of clock gene expression in NES patients depended on the individuals; some patients with NES showed similar clock gene expression rhythm to healthy subjects, and other patients with NES showed similar to DSWPD patients. Moreover, this study suggests that meal time after a long fast may influence more determination in clock gene expression rhythms than the time of breakfast. Therefore, this study also indicates that Per3 clock gene may be one of the parameters that will help us understand sleep and meal rhythm disturbances. [ABSTRACT FROM AUTHOR]

We found that strawberry (Fragaria x ananassa) extract has an IgE production suppressive activity and its oral administration improved skin manifestation in atopic dermatitis model mice. In present study, we identified an active substance using the IgE-producing human myeloma cell line U266. Gel filtration experiment indicated that the IgE suppressor was more than 6 kDa in molecular size. In addition, its pectinase treatment inhibited the activity, suggesting that the active substance in strawberry extract is pectin. Among solutions of water-(WP), hexametaphosphate-(HXP), acid-(HP) and alkali soluble pectin (OHP) extracted from strawberry, only OHP suppressed IgE production, and their suppressive activity was cancelled by pectinase treatment. In addition, OHP extracted from apple also inhibited IgE production. Furthermore, OHP also suppressed IgE production and did not affect IgG and IgM production in human peripheral blood mononuclear cells in an in vitro immunization condition. From these results, we concluded that OHP was an IgE suppressor in strawberry extract. [ABSTRACT FROM AUTHOR]

Background: Pseudohypoaldosteronism type II (PHAII) is a hereditary hypertensive disease caused by mutations in four genes: WNK1, WNK4, Kelch-like3 (KLHL3), and cullin3 (CUL3). Recently, it was revealed that CUL3-KLHL3 E3 ligase complex ubiquitinates WNK1 and WNK4, leading to their degradation, and that a common pathogenesis of PHAII is defective WNK degradation due to CUL3-KLHL3 E3 ligase complex impairment. PHAII-causing CUL3 mutations mediate exon9 skipping, producing a CUL3 protein with a 57-amino acid deletion (Δ403-459). However, the pathogenic effects of KLHL3, an adaptor protein that links WNKs with CUL3, in PHAII caused by CUL3 mutation remain unclear.Methods: To clarify detailed pathophysiological mechanisms underlying PHAII caused by CUL3 mutation in vivo, we generated and analyzed knock-in mice carrying the same CUL3 exon9 deletion (CUL3WT/Δex9) as that reported in PHAII patients.Results: CUL3WT/Δex9 mice exhibited a PHAII-like phenotype. Interestingly, we confirmed markedly decreased KLHL3 expression in CUL3WT/Δex9 mice by confirming the true KLHL3 band in vivo. However, the expression of other KLHL family proteins, such as KLHL2, was comparable between WT and mutant mice.Conclusion: KLHL3 expression was decreased in CUL3WT/Δex9 mice. However, expression levels of other KLHL family proteins were comparable between the wild-type and mutant mice. These findings indicate that the decreased abundance of KLHL3 is a specific phenomenon caused by mutant CUL3 (Δexon9). Our findings would improve our understanding of the pathogenesis of PHAII caused by CUL3 mutation in vivo. [ABSTRACT FROM AUTHOR]

Social jetlag has recently attracted attention as the circadian misalignment between biological and social clocks. We aimed to examine social jetlag and its effect on daytime sleepiness and daily functions in patients with narcolepsy, behaviorally induced insufficient sleep syndrome (BIISS) and delayed sleep-wake phase disorder (DSPD). The levels of social jetlag (SJLmid) and sleep-corrected social jetlag (SJLsc) were calculated for each patient, and the effect of these social jetlag-related parameters on daytime sleepiness and daily functions were examined. Objective sleepiness measured by the mean sleep latency in the multiple sleep latency test, subjective sleepiness assessed by the Epworth sleepiness scale (ESS), health-related quality of life (HRQoL) assessed by the SF-8 health survey, and incidences of mistakes in daily activities, traffic accidents and near-miss events related to daytime sleepiness were compared among the narcolepsy (n = 39), BIISS (n = 87) and DSPD (n = 28) groups. Both SJLmid and SJLsc showed a negative correlation with physical HRQoL in patients with narcolepsy and a positive correlation with the ESS score in patients with DSPD. In patients with BIISS, SJLsc reflected sleep loss rather than circadian misalignment; moreover, SJLsc was not associated with daytime sleepiness and daily functions. Social jetlag was not associated with incidences of mistakes in daily activities, traffic accidents and near-miss events. The state of social jetlag and its association with daily functions differed among the narcolepsy, BIISS and DSPD groups. Social jetlag represented sleep debt in BIISS, circadian misalignment in narcolepsy and both in DSPD. Our results thus show that the clinical manifestations and significance of social jetlag differ depending on the underlying sleep disorders. [ABSTRACT FROM AUTHOR]

The objective of the current review was to update the previous evidence-based medicine review of treatments for restless legs syndrome published in 2008. All randomized, controlled trials (level I) with a high quality score published between January 2007 and January 2017 were reviewed. Forty new studies qualified for efficacy review. Pregabalin, gabapentin enacarbil, and oxycodone/naloxone, which did not appear in the previous review, have accrued data to be considered efficacious. Likewise, new data enable the modification of the level of efficacy for rotigotine from likely efficacious to efficacious. Intravenous ferric carboxymaltose and pneumatic compression devices are considered likely efficacious in idiopathic restless legs syndrome. Bupropion and clonidine were reviewed, but the lack of data determined a rating of insufficient evidence for efficacy. The following interventions continue to be considered efficacious as in 2008: levodopa, ropinirole, pramipexole, cabergoline, pergolide, and gabapentin. Bromocriptine, oxycodone, carbamazepine, and valproic acid are considered likely efficacious. Oral iron is nonefficacious in iron-sufficient subjects, but its benefit for patients with low peripheral iron status has not been adequately evaluated. Restless legs syndrome augmentation has been identified as a significant long-term treatment complication for pramipexole more than pregabalin and possibly for all dopaminergic agents more than α2δ ligands. Therefore, special monitoring for augmentation is required for all dopaminergic medications as well as tramadol. Other drugs also require special safety monitoring: cabergoline, pergolide, oxycodone, methadone, tramadol, carbamazepine, and valproic acid. Finally, we also highlighted gaps and needs for future clinical research and studies of restless legs syndrome. © 2018 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Periodic limb movements during sleep (PLMS) are identified as a common finding in patients with restless legs syndrome (RLS). Although PLMS are observed in more than 80% of RLS patients in Western countries, little is known about Asian RLS patients and no data are available about Japanese patients. This cross-sectional study aimed to investigate ethnic differences in clinical information and polysomnographic variables including PLMS between Austrian and Japanese RLS patient undergoing nocturnal polysomnography (n-PSG). One hundred Austrian and 139 Japanese consecutive patients diagnosed with RLS who underwent n-PSG were included [Austrian 54.5 ± 13.6 years, 40 females (40%); Japanese 50.2 ± 18.9 years, 88 females (63.3%)]. Medical records and n-PSG data were reviewed retrospectively. Epidemiological, clinical and n-PSG variables were compared between the two groups. Rate of patients with PLMS ≥ 5/h and those with PLMS ≥ 15/h were higher in Austrian than in Japanese RLS patients (80.0 vs. 56.1%, P < 0.001; 55.0 vs. 41.7%, P = 0.043). Accordingly, Japanese RLS patients showed lower PLMS index than Austrian patients (21.3 vs. 33.6/h, P = 0.008). Japanese RLS patients showed higher female predominance, lower BMI, lower systolic/diastolic blood pressure, lower ferritin level and higher International restless legs syndrome severity scale than Austrian patients. None of these variables were associated with PLMS in both groups. Japanese RLS patients showed significantly lower comorbidity rate and lower indices of PLMS compared to Austrian RLS patients. This cross-sectional study on ethnic differences in PLMS in patients with RLS may provide a bridge to a future genetic comparative study between European and Asian RLS patients. [ABSTRACT FROM AUTHOR]

For prevention and early detection of dependence on hypnotics such as benzodiazepines (BZDs) or its agonists, a withdrawal symptom scale specialized for this kind of drug has long been sought. In this study, the benzodiazepine hypnotics withdrawal symptom scale (BHWSS) was developed using item response theory (IRT). This study enrolled 121 chronic insomnia patients (mean age 46.1 ± 15.6 years) who had been treated with hypnotics for 3 or more months. The patients were asked to fill a questionnaire that was developed by selecting questions from Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ) and Clinical Institute Withdrawal Assessment for Benzodiazepines (CIWA-B) on the basis of the symptoms triggered by reduction or abrupt cessation of the intake of hypnotics. A factor analysis was performed to verify the assumption that the new scale had one dimension. We drew item response category characteristic curves, following the IRT. Besides statistical considerations, clinical implications were also incorporated to select the 12 items used to construct the BHWSS questionnaire. Using the analyses based on IRT, 6 items each were selected from BWSQ and CIWA-B. The cumulative proportion of contribution of the first factor, obtained by factor analysis, was found to be 0.36. Cronbach’s α coefficient and McDonald’s ω coefficient were calculated to be 0.86 and 0.87, respectively. The total score of 12 items increased monotonically with the increasing level of withdrawal symptoms. The BHWSS could potentially become a practical tool for estimating the degree of BZD withdrawal symptoms. [ABSTRACT FROM AUTHOR]

Although cognitive behavioral therapy (CBT-I) has been recommended for the treatment of insomnia comorbid with psychiatric disorders and medical diseases, the effectiveness of CBT-I in such cases remains to be established. To fill this gap in the literature, we conducted a meta-analysis on the efficacy of CBT-I in the remediation of insomnia severity, important disease-related symptoms, and quality of life (QoL) in comorbid insomnia. A comprehensive literature search identified 30 randomized controlled trials (RCT) that were eligible for inclusion in the final analyses. Effect sizes were computed with Hedges' g, and study quality was evaluated using the Jadad scale. Analysis revealed that the effect sizes of the treatment were medium to large for important disease-related symptoms ( g = 0.60), insomnia severity ( g = 0.94), subjective and objective sleep onset latency ( g = 0.65 and g = 0.51, respectively), subjective waking after sleep onset ( g = 0.61), subjective and objective sleep efficiency ( g = 0.83 and g = 0.48, respectively), and sleep quality ( g = 0.80), but was small for health-related QoL ( g = 0.34) compared with a control group. At follow-up, the effect sizes of CBT-I were large for all outcome variables, but several large and significant heterogeneities were confirmed. CBT-I is an effective treatment for reducing the severity of insomnia and important disease-related symptoms of comorbid insomnia. [ABSTRACT FROM AUTHOR]

It is not known whether the endogenous mammalian core clock proteins sustain measurable oscillations in cells in culture wherede novotranslation is pharmacologically inhibited. We studied here the mammalian core clock protein PER2, which undergoes robust circadian oscillations in both abundance and phosphorylation. With a newly developed antibody that enables tracing the endogenous PER2 protein oscillations over circadian cycles with cultured mouse embryonic fibroblast cells, we provide evidence that PER2 does not persist noticeable circadian rhythms when translation is inhibited. [ABSTRACT FROM PUBLISHER]

Recent studies have also revealed the substantial efficacy of CBT-I not only for the severity of insomnia symptoms but also for important disease-related outcomes in chronic insomnia disorder comorbid with psychiatric diseases [[5]]. Many types of studies including meta-analyses have identified the effectiveness of cognitive behavioral therapy for insomnia (CBT-I) in the treatment of chronic insomnia disorder [[1]], and the therapy is currently recommended by insomnia treatment guidelines as the first-line treatment for the disorder [[3]]. In particular, a recent finding that response to insomnia treatment mediated eventual remission from depression suggested that focused effort to improve insomnia has the potential to enhance depression treatment outcomes [[7]]. [Extracted from the article]

We applied a neuroimaging analysis to investigate the association between neurocognitive decline and brain structural changes in patients with OSAS. Nineteen male patients with severe OSAS were enrolled. Correlations between sleep-breathing indices and microstructural changes were analyzed. SpO was positively correlated with ADC, FA, and white matter volumes in frontal areas, cingulate, anterior cerebellar lobe, and pons. A positive correlation with gray matter volume was identified in the bilateral parahippocampal gyri. Neurocognitive decline also correlated with minimum SpO value. Intermittent hypoxia in OSAS may cause microstructural axonal changes. These alterations may underlie executive dysfunction in OSAS. [ABSTRACT FROM AUTHOR]

The Polymer Sustained Alignment (PSA) technology is widely used for Liquid Crystal Display (LCD) TV application etc., because of its high transmittance, high contrast ratio and fast response. In this study, we have developed a novel high reactive and high reliable monomer for PSA. Also we found UV irradiation condition had a huge impact on Image Sticking issue, we propose the optimal UV condition for our new monomer too. [ABSTRACT FROM AUTHOR]

To investigate the rate of and risk factors for restless legs syndrome (RLS) augmentation in Japanese patients receiving pramipexole (PPX) treatment. Records of 231 consecutive patients with idiopathic RLS who received PPX therapy for more than one month in a single sleep disorder center were analyzed retrospectively. Augmentation was diagnosed based on the Max Planck Institute criteria; associated factors were identified by logistic regression analysis. Mean age at PPX initiation was 60.6 ± 14.9 years and mean treatment duration was 48.5 ± 26.4 months. Augmentation was diagnosed in 21 patients (9.1%). Daily PPX dose and treatment duration were significantly associated with augmentation. By analyzing the receiver operating characteristic curve, a PPX dose of 0.375 mg/day was found to be the optimal cut-off value for predicting augmentation. After stratifying patients according to PPX treatment duration, at median treatment duration of 46 months, optimal cut-off values for daily doses were 0.375 and 0.500 mg/day for <46 months and ≥46 months of treatment, respectively. The RLS augmentation with PPX treatment in Japanese patients was occurred at rate of 9.1%, being quite compatible with previously reported rates in Caucasian patients. The symptom could appear within a relatively short period after starting the treatment in possibly vulnerable cases even with a smaller drug dose. Our results support the importance of keeping doses of PPX low throughout the RLS treatment course to prevent augmentation. [ABSTRACT FROM AUTHOR]

Body temperature in homeothermic animals does not remain constant but displays a regular circadian fluctuation within a physiological range (e.g., 35°C–38.5°C in mice), constituting a fundamental systemic signal to harmonize circadian clock-regulated physiology. Here, we find the minimal upstream open reading frame (uORF) encoded by the 5′ UTR of the mammalian core clock gene Per2 and reveal its role as a regulatory module for temperature-dependent circadian clock entrainment. A temperature shift within the physiological range does not affect transcription but instead increases translation of Per2 through its minimal uORF. Genetic ablation of the Per2 minimal uORF and inhibition of phosphoinositide-3-kinase, lying upstream of temperature-dependent Per2 protein synthesis, perturb the entrainment of cells to simulated body temperature cycles. At the organismal level, Per2 minimal uORF mutant skin shows delayed wound healing, indicating that uORF-mediated Per2 modulation is crucial for optimal tissue homeostasis. Combined with transcriptional regulation, Per2 minimal uORF-mediated translation may enhance the fitness of circadian physiology. [Display omitted] • The circadian core clock gene Per2 possesses a minimal uORF in the 5′ UTR • The Per2 minimal uORF binds ribosomes at increased temperature • Circadian clock entrains to temperature via the Per2 minimal uORF through PI3K • The Per2 minimal uORF modulates translation and mediates skin tissue maintenance Miyake et al. identify a minimal upstream open reading frame (uORF) in the 5′ UTR of the core clock gene Per2 , which contributes to the circadian clock phase adaptation to day/night physiological body temperature cycles via the PI3K-mediated pathway. The Per2 minimal uORF mediates maintenance of skin tissue homeostasis. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate the level of daytime sleepiness in Japanese school-aged children and adolescents, and to examine associated factors including sleep loss and social jetlag using the Japanese version of the Pediatric Daytime Sleepiness Scale (PDSS-J). After the linguistic validation of the PDSS-J with a multi-step translation methodology, consisting of forward translation, back translation, expert review and cognitive debriefing interviews, we conducted a psychometric validation for 492 students aged 11–16 years (46.7% boys) of public elementary school, junior high school and high school, using the PDSS-J, the Karolinska Sleepiness Scale (KSS), and bedtimes and wake-up times on school days and free days. Internal consistency (Cronbach’s alpha) of the PDSS-J was 0.77, and the test–retest reliability demonstrated by the intraclass coefficient was 0.88. Multivariate logistic regression analysis revealed that both short sleep duration and social jetlag were identified as factors associated with daytime sleepiness, after adjustment for age and sex. PDSS-J scores were significantly higher in the group with large social jetlag with or without sufficient sleep duration than in the group with sufficient sleep duration and small social jetlag. The PDSS-J is an important tool for assessing daytime sleepiness, given its ease of administration and robust psychometric properties. The impact of not only sleep loss but also social jetlag on daytime sleepiness among school-aged children and adolescents must be fully taken into account. [ABSTRACT FROM AUTHOR]

Background: Obesity is known to be an important risk factor for OSA; however, OSA can also be seen in nonobese patients with a small maxilla and/or mandible as well as in all obese patients with such features. Thus, we hypothesized that regional factors, oropharyngeal crowding associated with fat deposition, and maxillomandibular enclosure size closely related to the severity of OSA.Methods: A total of 703 male Japanese subjects were enrolled; theywere classified into obese (BMI ≥ 30 kg/m(2); n = 158) and nonobese (BMI < 30 kg/m(2); n = 545) groups. Using lateral cephalometric analysis, we measured the tongue size (TG), lower face cage (LFC), and TG/LFC ratio (ie, oropharyngeal crowding) to evaluate the state of upper airway crowding. The correlations between these cephalometric measurements and BMI, age, and the apnea-hypopnea index (AHI) were evaluated.Results: In obese subjects, the TG/LFC ratio, BMI, and TG positively correlated with AHI, whereas, in nonobese subjects, age, BMI, and TG/LFC significantly correlated with AHI. Subsequent stepwise multiple linear regression analysis revealed that the variables associated with AHI differed between obese and nonobese OSA subjects, although BMI and TG/LFC were significantly associated with AHI in both groups. In particular, the contribution of TG/LFC to AHI was larger than that of BMI in the obese group.Conclusions: Oropharyngeal crowding is a local anatomic factor that independently relates to the severity of OSA in both obese and nonobese patients; the more crowded the upper airway, the more severe the OSA. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that there are certain pathophysiological relationships between bipolar disorder (BD) and circadian rhythm dysfunction. However, apparently no studies have clarified the prevalence of circadian rhythm sleep-wake disorders (CRSWD) in patients with BD. This study was set out to investigate the prevalence of CRSWD and associated factors in patients with BD. One hundred four euthymic BD outpatients participated in this study. The subjects were asked to answer questionnaires including demographic variables, clinical course of BD, and family history of psychiatric disorders and suicide. Severity of BD was assessed by the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. CRSWD was diagnosed by clinical interview, together with sleep logs, according to the International Classification of Sleep Disorders, third edition (ICSD-3). Thirty-five subjects (32.4%) met the criteria for CRSWD. The age at the time of investigation and that at the onset of BD were both lower in the CRSWD group than in the non-CRSWD group. The rates of family history of psychiatric disorders and suicide in the CRSWD group were higher than those in the non-CRSWD group. Multiple logistic regression analysis revealed that the presence of CRSWD was significantly associated with younger onset age of BD and family history of suicide. The prevalence of CRSWD could be quite high in BD patients. Younger onset age of BD and family history of suicide were associated with presence of CRSWD in BD patients. [ABSTRACT FROM AUTHOR]

We evaluated the impact of migraine and restless legs syndrome (RLS) comorbidity on sleep and mood using two different clinical settings (Study 1, 33 RLS patients from a multicenter study; Study 2, 262 active migraine patients from a single-center study). Although the presence of migraine in RLS patients was not correlated with sleep problems or depressive symptoms (Study 1), the presence of RLS in active migraine patients was associated with poor sleep quality, daytime sleepiness and depressive symptoms (Study 2). RLS is an important comorbidity associated with active migraine; however, the clinical setting in particular may influence the RLS–migraine association. [ABSTRACT FROM AUTHOR]