Sleep‐related eating disorder (SRED) is a condition characterized by recurrent episodes of eating at the transition from night‐time sleep to arousal. SRED patients describe eating in an ...out‐of‐control manner with preference for high‐caloric foods and sometimes with inedible or toxic items. Level of consciousness during SRED episodes ranges from partial consciousness to dense unawareness typical of somnambulistic episodes. SRED is sometimes associated with psychotropic medication, in particular sedative hypnotics, and other sleep disorders, including parasomnias, narcolepsy, and restless legs syndrome. Night eating syndrome (NES) is another important condition in the disordered night‐time eating spectrum showing hyperphagia episodes at full arousal from nocturnal sleep without accompanying amnesia. NES could be considered an abnormality in the circadian rhythm of meal timing with a normal circadian timing of sleep onset. The two conditions often overlap and possibly share a common pathophysiology. Studies have suggested that central nervous system serotonin modulation may lead to an effective treatment of NES, while the anti‐seizure medication topiramate may be an effective SRED treatment.
Aim
The aim of this study was to develop and validate a Japanese version of the Athens Insomnia Scale (AIS‐J).
Methods
The AIS‐J was created using a back‐translation design. A total of 477 ...outpatients with chronic insomnia and 163 individuals from the general community were recruited. Participants were asked to complete the AIS‐J along with two other insomnia scales – Japanese versions of the Pittsburgh Sleep Quality Index and the Insomnia Severity Index.
Results
The AIS‐J consisted of a two‐factor structure: ‘nocturnal sleep problem’ (items 1–5) and ‘daytime dysfunction’ (items 6–8). Internal consistencycoefficients ranged from 0.78 to 0.88. Correlations between the AIS‐J and the aforementioned authorized scales were 0.81 and 0.85, respectively. Scores on the AIS‐J were significantly higher for the insomnia group than for the control group. The AIS‐J cut‐off value for identifying pathological insomnia was estimated at 6 points or more, and the AIS‐J‐nocturnal cut‐off value was estimated at 4 points or more.
Conclusions
The AIS‐J has sufficient validity and diagnostic utility.
Temperature-dependent translational control of the core clock gene Per2 plays an important role in establishing entrainment of the circadian clock to physiological body temperature cycles. ...Previously, we found an involvement of the phosphatidylinositol 3-kinase (PI3K) in causing Per2 protein expression in response to a warm temperature shift (WTS) within a physiological range (from 35 to 38.5 °C). However, signaling pathway mediating the Per2 protein expression in response to WTS is only sparsely understood. Additional factor(s) other than PI3K remains unknown. Here we report the identification of eukaryotic initiation factor 2α (eIF2α) kinases, protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK), as a novel mediator of WTS-dependent Per2 protein expression. Canonically, eIF2α has been regarded as a major downstream target of PERK and PKR. However, we found that PERK and PKR mediate WTS response of Per2 in a manner not involving eIF2α. We observed that PERK and PKR serve as an upstream regulator of PI3K rather than eIF2α in the context of WTS-dependent Per2 protein expression. There have been studies reporting PI3K activation occurring depending on PERK and PKR, while its physiological contribution has remained elusive. Our finding therefore not only helps to enrich the knowledge of how WTS affects Per2 protein expression but also extends the region of cellular biology involving the PERK/PKR-mediated PI3K activation to include entrainment-mechanism of the circadian clock.
Time-resolved direct observations of proteins in action provide essential mechanistic insights into biological processes. Here, we present mechanisms of action of protein disulfide isomerase ...(PDI)-the most versatile disulfide-introducing enzyme in the endoplasmic reticulum-during the catalysis of oxidative protein folding. Single-molecule analysis by high-speed atomic force microscopy revealed that oxidized PDI is in rapid equilibrium between open and closed conformations, whereas reduced PDI is maintained in the closed state. In the presence of unfolded substrates, oxidized PDI, but not reduced PDI, assembles to form a face-to-face dimer, creating a central hydrophobic cavity with multiple redox-active sites, where substrates are likely accommodated to undergo accelerated oxidative folding. Such PDI dimers are diverse in shape and have different lifetimes depending on substrates. To effectively guide proper oxidative protein folding, PDI regulates conformational dynamics and oligomeric states in accordance with its own redox state and the configurations or folding states of substrates.
Abstract
Study Objectives
To evaluate the prevalence and clinical characteristics of isolated REM sleep behavior disorder (iRBD) among a general population of elderly Japanese people.
Methods
This ...epidemiological study targeted 2714 elderly residents (76.0 ± 8.0 years, 52.9% female) of a rural community. Questionnaires including the REM sleep behavior disorder single question and demographic information were distributed. All respondents with the question positive were interviewed by telephone. Respondents suspected of having iRBD proceeded to face-to-face interviews and underwent video-polysomnography and neurological/neuropsychological examination. These results were compared to those of previously diagnosed clinical iRBD patients in our sleep clinic.
Results
Of 1464 respondents to the questionnaire, 18 respondents were diagnosed as iRBD (1.23 0.66–1.79%), including eight respondents who satisfied diagnostic criteria with REM sleep without atonia (RWA) above the cut-off value (0.54 0.17–0.92%) and 10 respondents who had clear dream enactment behaviors but not RWA above the cut-off (provisionally diagnosed iRBD; p-iRBD) (0.69 0.26–1.11%). Severity of RBD and RWA of the population-based iRBD were compatible with those of the clinical iRBD. Half of the population-based iRBD showed orthostatic hypotension and they showed lower olfactory function than population-based p-iRBD and non-RBD. However, their olfactory and cognitive functions were higher than those in the clinical iRBD patients.
Conclusions
Prevalence of iRBD in Japanese elderly people was comparable with the rate reported from other countries. Population-based iRBD/p-iRBD showed lower neurodegenerative loading than clinical iRBD in spite of comparable disease duration of RBD, that may indicate their lower risk of future neurodegeneration.
Previous meta-analyses have shown the effectiveness of cognitive behavioral therapy for insomnia (CBT-I). However, conclusive information about therapeutic effects (especially during follow-up), ...effect sizes of objective sleep parameters and self-rating scales, and the problem of publication bias has not been obtained. We conducted a meta-analysis focusing on these issues. We identified 14 randomized controlled studies published between 1990 and 2009 that fulfilled our selection criteria. Intra-group comparison of CBT-I and comparison between CBT-I and control groups were performed on these studies. The intra-group comparison revealed that the effect sizes of CBT-I for subjective sleep variables from sleep diaries were medium to large at the end point of treatment, and these effect sizes were favorably maintained on follow-up. A between-group comparison revealed that CBT-I was more effective than the control for subjective sleep variables at the end of treatment and that its effectiveness was also recognized on follow-up. With regard to self-rating scales, as compared to the control group, the effect sizes in the CBT-I group were medium to large both at the end of treatment and on follow-up. However, there were problems of publication bias in some of the subjective or objective sleep variables. The abovementioned results support the effectiveness of CBT-I for the treatment and prevention of relapse of primary insomnia despite the existence of a certain publication bias.
Abstract Objective Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for dementia development in patients with Parkinson’s disease (PD); however, the role of subclinical RBD ...remains unknown. Patients with PD and clinical RBD, subclinical RBD, or with normal REM sleep were examined in a cross sectional study and a longitudinal follow-up. Methods Interviews regarding RBD symptoms and polysomnographies were performed on 82 PD patients divided into RBD subcategories based on the presence/absence of REM sleep without atonia (RWA) and/or RBD symptoms. Descriptive variables were compared and patients were followed-up longitudinally for 21.4 ± 10.8 months. Results The existence of RBD, but not subclinical RBD, was associated with orthostatic hypotension and levodopa dose equivalents (LDEs) in patients with PD. Kaplan–Myer curves indicated that the occurrence of dementia in the PD group with clinical RBD was significantly faster than in the PD group with normal REM sleep ( p = 0.013). A Cox hazard regression analysis revealed that development to PD with dementia was only significantly associated with the presence of clinical RBD (hazard ratio: 14.1, p = 0.017). Conclusion Clinical RBD symptoms, but not subclinical RBD, were associated with the development of dementia in PD.
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.
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