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Objective. The Spontaneously Diabetic Torii (SDT) fatty rat, established by introducing the fa allele (obesity gene) of the Zucker fatty rat into the SDT rat genome, is a new model of obese type 2 diabetes. We studied the pathologic features of diabetic retinopathy (DR) in this animal. Methods. The eyes of SDT fatty, SDT (controls), and Sprague Dawley (SD) rats (normal controls) were enucleated at 8, 16, 24, 32, and 40 weeks of age (n=5‐6 for each rat type at each age). The retinal thicknesses, numbers of retinal folds, and choroidal thicknesses were evaluated. Immunostaining for glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was performed. Quantitative analyses of the immunopositive regions were performed using a cell-counting algorithm. Results. The retinas tended to be thicker in the SDT fatty rats and SDT rats than in the SD rats; the choroids tended to be thicker in the SDT fatty rats than in the SD rats. The retinal folds in the SDT fatty rats developed earlier and were more severe than in the SDT rats. Quantitative analyses showed that the GFAP- and VEGF-positive regions in the retinas of the SDT fatty rats were significantly larger than those of the SDT rats. Conclusions. SDT fatty rats developed more severe DR earlier than the SDT rats. The SDT fatty rats might be useful as a type 2 diabetes animal model to study DR.

STUDY OBJECTIVES: The objective of this study was to determine the efficacy of ramelteon in treating abnormal eating behavior in patients with sleep-related eating disorder and/or night eating syndrome. METHODS: We retrospectively reviewed the medical records of patients with sleep-related eating disorder/night eating syndrome at the Yoyogi Sleep Disorder Center from November 2013 to November 2018. We categorized patients as ramelteon treatment responders when the frequency of nighttime eating per week decreased to less than half of that before treatment. RESULTS: Forty-nine patients were included in the analysis. The mean frequency of eating behavior (per week) (standard deviation) at baseline and post-ramelteon treatment was significantly different, at 5.3 (2.2) and 3.2 (3.0), respectively (P < .001). Twenty-one patients (42.9%) were classified as responders. Adverse events, all of which were mild daytime somnolence, were observed in 5 patients. There were significantly more individuals using benzodiazepine derivatives and Z-drugs before treatment and those with coexisting delayed sleep-wake phase disorder in the responder group than in the nonresponder group (P < .001 and P < .05, respectively). The mean benzodiazepine derivatives and Z-drugs dose significantly decreased from baseline to post-ramelteon treatment within the responder group (P < .05). This trend was not observed in the nonresponder group. Meanwhile, the sleep midpoint of patients with sleep-related eating disorder/night eating syndrome and delayed sleep-wake phase disorder did not significantly change after treatment. CONCLUSIONS: Our results indicate that ramelteon is a candidate treatment for sleep-related eating disorder/night eating syndrome. The effects of ramelteon might have occurred primarily through the reduction in benzodiazepine derivatives and Z-drugs rather than through the improvement in sleep-wake rhythm dysregulation. CITATION: Matsui K, Kuriyama K, Kobayashi M, Inada K, Nishimura K, Inoue Y. The efficacy of add-on ramelteon and subsequent dose reduction of benzodiazepine derivatives/Z-drugs for the treatment of sleep-related eating disorder and night eating syndrome: a retrospective analysis of consecutive patients. J Clin Sleep Med. 2021;17(7):1475–1483.

This study aimed to refine and validate the Benzodiazepine Hypnotics Withdrawal Symptom Scale (BHWSS). The 12-item prototype version of the BHWSS was administered to a sample of 346 patients with chronic insomnia (161 males and 185 females, mean age: 52.8 ± 16.6 years) who had been taking hypnotics (benzodiazepines [BZDs] or BZD receptor agonists) for at least 3 months. The item information curve indicated that two of the 12 BHWSS items should be excluded. As a result of analyzing the 10-item version of the BHWSS (revised-BHWSS), the contribution rate in the case of the factor 1 was 0.49, Cronbach's α was 0.90, and the reliability coefficient ω was 0.91. An analysis of the item information curve for the revised-BHWSS indicated that the information amount per item increased from 3.90 for the original 12-item BHWSS to 4.37 for the 10-item revised-BHWSS. The receiver operating characteristic curve indicated that 6.5 points on the revised-BHWSS was the most appropriate cutoff for estimating moderate or severe withdrawal symptoms using the Benzodiazepine Dependence Self-Report Questionnaire as a reference. These results suggest that the 10-item revised-BHWSS has sufficient reliability and validity for evaluating the severity of withdrawal symptoms after discontinuing BZDs.

Objective The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) might be applicable for assessing delayed sleep-wake phase disorder (DSWPD). We aimed to investigate the reliability and validity of the Japanese version of the BRIAN self-report (J-BRIAN-SR) in DSWPD patients and determine a cutoff score to identify the presence of the disorder. Methods We enrolled 60 newly diagnosed DSWPD outpatients and 64 age-matched healthy controls. We used Cronbach's alpha for internal reliability to evaluate J-BRIAN-SR. We confirmed the reliability of the A test and re-test using Pearson's correlation coefficient in the controls. We used confirmatory factor analysis to evaluate the factor structure of J-BRIAN-SR and referenced the Morningness-Eveningness Questionnaire (MEQ) to check concurrent validity. We analyzed the receiver operating characteristic curve (ROC) to determine the J-BRIAN-SR cutoff point for the presence of DSWPD. Results The 18-component scores of the J-BRIAN-SR had an overall reliability coefficient (Cronbach's alpha) of 0.82. We confirmed a high test-retest reliability using an intraclass correlation coefficient (r = 0.84). The correlation between J-BRIAN-SR and MEQ was 0.38 (p = 0.003). The J-BRIAN-SR that we extracted by exploratory factor analysis consisted of three factors. A score of 40 points provided a sensitivity of 80.0% and a specificity of 75.6% for the positivity of DSWPD. Conclusions The results of the present study revealed that J-BRIAN-SR is a valid and reliable instrument for screening and evaluating the severity of DSWPD. Our findings will be useful to physicians and patients in Japan and those in clinical settings.

Purpose To determine risk factors and clinical signs for severe Acanthamoeba keratitis (AK) by comparing severe cases with mild cases with good prognosis. Patients and methods We reviewed medical records of ten cases of AK (five males and five females) referred to our hospital and classified cases into two groups. One eye that required therapeutic keratoplasty and three eyes with a poor visual acuity (

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.

We assessed the validity of using a sheet-shaped body vibrometer (SBV) as a portable monitoring device for obstructive sleep apnea (OSA) screening. Seventy consecutive patients with suspected OSA underwent simultaneous in-laboratory polysomnography (PSG) and SBV. We evaluated the screening accuracy of the respiratory event index (REI) obtained with the SBV, using the REI based on either the estimated total sleep time (REI_eTST) or time in bed (REI_TIB); these were compared to the apnea-hypopnea index (AHI) obtained via PSG. Bland-Altman plots indicated that the mean difference between REI_eTST and AHI was lower than that between REI_TIB and AHI (1.2 ± 19.8 vs. 6.5 ± 16.8). For AHI ≥ 15, the sensitivity and specificity at an optimal REI_eTST of 17.0 were 90.9% and 76.9%, whereas those at an optimal REI_TIB of 15.9 were 86.4% and 80.8%, respectively; moreover, for AHI ≥ 30, these values at an optimal REI_eTST of 26.0 were 89.5% and 88.2%, whereas those at an optimal REI_TIB of 23.8 were 84.2% and 92.2%, respectively. The optimal cutoff values of REIs for AHI of ≥ 5 were markedly different from those for AHI obtained via PSG (REI_eTST, 14.9; REI_TIB, 15.0), but close to those for AHI of ≥ 15; both had good sensitivities and specificities. REIs obtained via SBV performed well in moderate-to-severe, but not mild, OSA screening; REI_eTST showed a slightly higher sensitivity and a relatively closer value to the AHI obtained via PSG when compared to REI_TIB. We consider the SBV less acceptable for screening mild cases than more severe cases.

Positional obstructive sleep apnea (P-OSA) is a clinically common phenotype of OSA, which can be treated effectively with mandibular advancement devices (MADs). We hypothesized that the efficacy of an MAD is comparable to that of nasal continuous positive airway pressure (nCPAP) in P-OSA patients.Among patients diagnosed with OSA at a single sleep center from January 2008 to May 2014, male subjects with moderate OSA were recruited and stringently categorized as having P-OSA when the ratio of their lateral apnea-hypopnea index (AHI) to supine AHI was ≤ 0.5, their lateral sleep time was60 minutes, and their lateral REM sleep time was longer than 10 minutes. Treatment efficacy was compared between P-OSA subjects with an MAD (n = 34) and those with nCPAP (n = 34) after matching for age, body-mass index, and baseline AHI.There were no significant differences in baseline AHI (MAD: nCPAP = 20.6 ± 3.9/h: 21.3 ± 1.7/h, p = 0.35) or in follow-up AHI (MAD: nCPAP = 4.7 ± 3.5/h: 3.4 ± 3.7/h, p = 0.12) between the 2 treatment groups, and hence MADs lowered the AHI to the same extent as nCPAP.These findings suggest that an MAD is as efficacious as nCPAP for P-OSA patients. MAD treatment for this specific phenotype may be a promising patient-tailored and first-line approach to OSA.A commentary on this article appears in this issue on page 1079.

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. 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. 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. 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.

To clarify the significance of melatonin secretion under intensive care conditions, we investigated melatonin secretion profiles and sleep parameters of 23 patients just after admission to the coronary care unit (CCU) and 19 age-matched controls. Sleep parameters were evaluated by actigraphy, and melatonin secretion was assessed by measuring the urinary 6-sulphatoxy melatonin (6-SMT). 6-SMT secretion was lower and nocturnal sleep parameters were less satisfactory in the subjects than those in the controls, and there were positive correlations between these variables, particularly in the subject patients. The lowered melatonin secretion might be involved in the mechanism of insomnia in CCU patients.

Objective Our study was conducted to validate the Japanese version of the Ford Insomnia Response to Stress Test (FIRST-J) and to clarify the association of the measure with trait anxiety and insomnia in healthy subjects and insomnia patients. Methods We studied 161 healthy subjects and 177 insomnia patients who completed the FIRST-J, Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS), and State-Trait Anxiety Inventory-Trait (STAI). The healthy subjects and the insomnia patients were classified, respectively, into two groups with high FIRST-J and low FIRST-J scores (divided by the median value of healthy subjects). Results Cronbach α coefficients of the FIRST-J in the insomnia patients and healthy subjects were 0.89 and 0.87, respectively. Factor analysis revealed that the FIRST-J had a single-factor structure. The FIRST-J score significantly correlated with all other measures in the healthy subjects, though the score only correlated with the score of the STAI in the insomnia patients. The healthy subjects with high FIRST-J scores showed higher scores of the AIS and STAI than those with low FIRST-J scores. Furthermore, insomnia patients had a higher total score of the FIRST-J than the healthy subjects. Conclusions The FIRST-J is an important tool for assessing vulnerability to insomnia.

The status of night-to-night variability for periodic limb movements in sleep (PLMS) has not been clarified. With this in mind, we investigated the validity of PLMS measurement by actigraphy with the PAM-RL device in Japanese patients with suspected restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) and the night-to-night variability of PLMS among the subjects.Forty-one subjects (mean age, 52.1±16.1 years) underwent polysomnography (PSG) and PAM-RL measurement simultaneously. Thereafter, subjects used the PAM-RL at home on four more consecutive nights.The correlation between PLMS index on PSG (PLMSI-PSG) and PLM index on PAM-RL (PLMI-PAM) was 0.781 (P.001). When the PLMSI cutoff value on PSG was set at 15 episodes per hour, the cutoff value for predicting this PLMSI level was 16.0 episodes per hour. When the condition was set to the level in which the mean interclass correlation coefficient reached ≥0.9, the number of required nights for repeated measurements was 26 nights for subjects with PLMI of15 episodes per hour and three nights for those with PLMI ≥15 episodes per hour on PAM-RL.PAM-RL is thought to be valuable for assessing PLMS even in Japanese subjects. Recording of PAM-RL for three or more consecutive nights may be required to ensure the screening reliability of a patient with suspected pathologically frequent PLMS.

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. Language: en

Recently, medical applications of radiation have been widely spread. However, exposure of medical staffs is sometimes not focused on because treatment of patients is the first priority. It is thus important to decrease exposure for them as much as possible. The purpose of this study is to develop a system which can measure energy spectrum and dose of gamma-rays at the same time in real time in medical application spots. As a result, the medical staff could be guided to aware the risk of radiation and finally the exposure dose to them could be suppressed substantially. We first decided to use a CsI(Tl) scintillator as the gamma-ray detection device. A Multi-Pixel Photon Counter (MPPC) was attached to the scintillator to detect gamma-ray signals. Pulse height spectra were measured with several standard gamma-ray sources. The detection efficiency and energy resolution were deduced from the measured results and the detection efficiency was compared with the calculation result by MCNP5. After evaluating the response function, the energy spectrum was derived with the spectrum type Bayesian estimation and the sequential Bayesian estimation procedure. From the result, it was confirmed that the sequential Bayesian estimation could be applied to real time measurement of gamma-ray energy spectrum and dose.

The SD-101 is a non-restrictive sheet-like medical device that measures sleep-disordered breathing using pressure sensors that can detect the gravitational alterations in the body that accompany respiratory movement. One report has described that the screening specificity of the SD-101 for mild to moderate obstructive sleep apnea syndrome (OSAS) is relatively low. The present study examines whether the accuracy of the SD-101 for OSAS screening is improved by simultaneously measuring percutaneous oxygen saturation (SpO2).Sixty consecutive individuals with suspected OSAS consented to undergo overnight polysomnography (PSG) together with simultaneous measurements of SD-101 and SpO2 at our laboratory.The apnea-hypopnea index (AHI) determined from PSG and the respiratory disturbance index determined from SD-101 measurements significantly correlated (SD-101 alone: r = 0.871, p 0.0001; SD-101 with SpO2: r = 0.965, p 0.0001). Bland-Altman plots showed a smaller dispersion for the SD-101 with SpO2 than for the SD-101 alone. The SD-101 with SpO2 detected an AHI of15 on PSG with a sensitivity and specificity of 96.9 and 90.5 % compared with 87.5 and of 85.7 %, respectively, of the SD-101 alone.Simultaneously measuring SpO2 improved the accuracy of the SD-101 for OSAS screening. Furthermore, this modality appears to offer high sensitivity and specificity for detecting even moderately severe OSAS.

Objective To assess the quality of life of patients with narcolepsy with cataplexy (NA–CA), narcolepsy without cataplexy (NA w/o CA), and idiopathic hypersomnia without long sleep time (IHS w/o LST) who were taking psychostimulant medication, and to ascertain which factors (including psychosocial and environmental variables) influence quality of life in this population. Methods In total, 185 patients who had received regular treatment were enrolled in the study (NA–CA, n =83; NA w/o CA, n =48; IHS w/o LST, n =54). Patients were asked to complete questionnaires including the Short Form-36 Health Survey (SF-36), the Epworth Sleepiness Scale (ESS), and items concerning psychosocial and environmental variables. Results All three diagnostic groups had significantly lower scores for most SF-36 domains compared with the Japanese normative data, and the ESS score was significantly reduced with treatment. Multiple logistic regression analyses revealed that several SF-36 domains were associated with the ESS score; autonomy in controlling own job schedule, experience of divorce or break up with a partner due to symptoms, experience of being forced to relocate or being dismissed due to symptoms, and perception of support from others. Conclusions The severity of subjective sleepiness and psychological and environmental variables influenced quality of life in patients with these hypersomnias of central origin.

The miscibility of microbial poly(ε- L -lysine)/carboxymethyl cellulose sodium salt (ε-PL/CMC) blends was investigated by solid-state nuclear magnetic resonance methods. 1 H spin-lattice relaxation time in the laboratory frame T1, and in the rotating frame, T1ρ measurements indicate that the blends are miscible at all compositions on a scale of 2–5 nm. Formation of carbamates and its reversibility were examined. ε-PL/CMC hydrogel was formed by bubbling carbon dioxide gas into ε-PL and CMC aqueous solution mixture.

Obstructive sleep apnea (OSA) is a common, but underdiagnosed, public health problem that predisposes the patient to higher cardiovascular morbidity and mortality. Nasal continuous positive airway pressure (nCPAP) has been established as a standard treatment for OSA for nearly three decades, whereas oral appliances (i.e., mandibular repositioning splint and tongue retaining device) have been prescribed for patients with mild to moderate OSA and/or who have failed to respond to nCPAP [1–3]. A tongue retaining device is particularly recommended in patients who are contraindicated for mandibular repositioning splints due to an insufficient number of teeth, severe periodontal disease, temporomandibular joint problems, and so on [1]. To improve the patency of the pharyngeal airway, this device holds the tongue at a protruded position by negative pressure that is generated within the anterior socket, thus possibly displacing the tongue base ventrally. Dort and Brant [4] succeeded in reducing the respiratory disturbance index (from a baseline of 15.5±17.6 to 8.9±7.6 at follow-up) with a tongue retaining device that had an improved anterior socket for tongue suction. There have also been a few reports on the efficacy of, compliance with, and indications for a tongue stabilizing device [5–7], which is considered to be a type of tongue retaining device. In a pilot study, Kingshott et al. [5] first documented that a tongue stabilizing device reduced the severity of snoring and microarousals. Deane et al. [6] later demonstrated that a tongue stabilizing device was as efficacious as a mandibular repositioning splint in terms of reducing the apnea– hypopnea index (AHI), but noted that a lower compliance was observed with the tongue stabilizing device when both appliances were offered. After the Fukushima Daiichi Nuclear Power Plant accident that occurred right after the East Japan earthquake, Tsuiki et al. [7] proposed that a tongue stabilizing device could be a first-line treatment modality for snorers with suspected OSA at temporary refuges because of its simplicity. Although these reports describe certain favorable results with tongue retaining devices, strong evidence indicating the effectiveness of the device is still limited. Clinically, incomplete tongue suction often fails to hold the tongue, leading to unsatisfactory outcomes. Moreover, the tongue retaining device does not involve alternative methods when the suction pressure is incomplete. This may result in an overall lower effectiveness of tongue retaining devices [2] in comparison with mandibular repositioning splints. S. Tsuiki :K. Maeda :M. Kobayashi : T. Sasai :Y. Takahashi : Y. Inoue Neuropsychiatric Research Institute, Tokyo, Japan

Summary A large tongue is recognised as a factor that increases the collapsibility of the upper airway in obstructive sleep apnoea (OSA) patients. We hypothesised that the propensity to develop severe OSA could be minimised if the dental arches were enlarged in obese OSA people who are thought to have a large tongue. We therefore compared the size of the dental arches in obese and non-obese OSA patients. Using a lateral cephalogram and study models, we compared the sizes of the tongue and dental arches in 23 obese and 23 non-obese Japanese male OSA patients, who were matched for age, apnoea hypopnea index (AHI) and maxillomandibular size. The median age (years) and AHI (events per hour) for the obese and non-obese groups were 36·5 and 39·0, and 13·4 and 14·3, respectively. The maxillomandibular size was matched with regard to SNA, SNB and lower face cage obtained from cephalometric measurements. The parameters that were measured for the study model included dental arch width, dental arch length, overjet and overbite. Tongue size (P

Background: Morbidity due to obstructive sleep apnea syndrome (OSAS) is increased in the elderly population. However, the clinical characteristics of OSAS in elderly patients have not been characterized conclusively. The aim of this study was to clarify differences in clinical characteristics of OSAS between patients with middle-age onset and elderly onset of OSAS. Methods: Patients with OSAS aged 65 years were classifi ed into groups according to age at fi identifi cation of respiratory pauses during sleep: a middle-age onset group (n 5 32) where onset was at age , 50 years and an elderly onset group (n 5 31) where onset was at age 60 years. We compared demographic variables; polysomnographic variables; daytime sleepiness measures, including the multiple sleep latency test (MSLT) and the Epworth sleepiness scale (ESS); and adequate level of nasal continuous positive airway pressure (CPAP) between groups. Results: BMI and frequency of underlying cardiovascular disorder were lower in the elderly onset group than in the middle-age onset group. No signifi cant differences in apnea-hypopnea index or percentage of the period showing O 2 desaturation were seen between groups. However, arousal index, maximal negative esophageal pressure value, and adequate nasal CPAP level were signifi cantly smaller in the elderly onset group. Mean sleep latency on MSLT was longer, and ESS score was lower in the elderly onset group. Conclusions: Compared with the middle-age onset group, the clinical signifi cance of OSAS in the elderly onset group seemed to remain milder. This fi nding is possibly because of the smaller physiologic response to respiratory events.

The loss of dopaminergic (DA) neurons in the substantia nigra (SN) is a major pathophysiological feature of patients with Parkinson's disease (PD). As nigral DA neurons contain both neuromelanin (NM) and dopamine transporter (DAT), decreased intensities in both NM-sensitive MRI and DAT PET reflect decreased DA neuronal density. This study demonstrates that a more specific metric for the nigral DA neuronal density can be derived with multimodal MRI and PET. Participants were 11 clinically diagnosed PD patients and 10 age and gender matched healthy controls (HCs). Two quantities, the NM-related index (RNM) and the binding potential of the radiotracer [18F]FE-PE2I to DAT (BPND) in SN, were measured for each subject using MRI and PET, respectively. Principal component analysis (PCA) was applied to the multimodal data set to estimate principal components. One of the components, PCP, corresponds to a basis vector oriented in a direction where both BPND and RNM increase. The ability of BPND, RNM and PCP to discriminate between HC and PD groups was compared. Correlation analyses between the motor score of the unified Parkinson's disease rating scale and each metric were also performed. PCP, BPND and RNM for PD patients were significantly lower than those for HCs (F = 16.26, P

Narcolepsy (NA) is a sleep disorder characterized by excessive daytime sleepiness and an increased propensity of rapid eye movement sleep. If left untreated, NA can lead to academic underachievement or job loss because of dozing off or mistakes caused by inattentiveness due to sleepiness. Although untreated narcolepsy patients may suffer from many social disadvantages due to excessive daytime sleepiness, mostly it takes a long time to receive a definitive diagnosis of the disorder. This retrospective study investigated factors related to the period until definitive diagnosis among patients with narcolepsy in Japan. We enrolled 181 consecutive patients (108 men, 73 women; mean age 37.6 ± 16.6 years old; narcolepsy with cataplexy/narcolepsy without cataplexy = 131:50). Multivariate logistic regression analysis was performed with period until definitive diagnosis as the dependent variable and descriptive clinical variables as the independent variables. The mean period until receiving the diagnosis among the participants was 9.9 ± 10.1 years. More than half of the patients first learned about the disorder from information provided by the media. Multivariate logistic analysis indicated that adult onset (p

The aggravation of obstructive sleep apnoea syndrome (OSAS) is reportedly associated with weight gain. The present study investigated the factors associated with worsening of respiratory functional parameters in Japanese OSAS patients who showed no body weight change during the follow-up period. A follow-up polysomnography (PSG) was performed in 82 patients with a mean of 7.5 years after the diagnostic PSG, and the apnoea–hypopnoea index (AHI), respiratory event duration, minimum percutaneous oxygen saturation (SpO2), baseline SpO2, and 3 % oxygen desaturation index (ODI) during sleep were compared between the two PSGs. Furthermore, factors associated with worsened AHI, respiratory event duration, and minimum SpO2 were investigated using logistic regression analysis. No significant differences were observed in AHI, baseline SpO2, and 3 % ODI between the two PSGs. However, there was a significantly increased respiratory event duration and decreased minimum SpO2 observed. In addition, 17 patients had a ≥25 % AHI increase, and the age of 40–60 years and initial OSAS severity (mild and moderate) were the significantly associated factors. Age of ≥60 years and a baseline body mass index (BMI) of ≥25 kg/m2 were significantly associated with prolonged respiratory event duration. The age of 40–60 years was significantly associated with decreased minimum SpO2. Untreated middle-aged patients may be at a high risk for worsened AHI and SpO2 even without weight gain.

We investigated daytime dysfunction in children with restless legs syndrome (RLS) and the effects of treatment primarily with iron supplements on RLS symptoms and daytime dysfunction. We recruited 25 children with RLS (male:female=6:19, mean age at study onset: 12.3 years) for this prospective study, assessing their demographics, symptomatic characteristics, serum ferritin levels, and daytime functioning using the ADHD Rating Scale IV (ADHD-RS-IV), the Pediatric Symptom Checklist (PSC), and the Pediatric Quality of Life Inventory (PedsQL™). Children with RLS were compared with 28 controls (male:female=10:18, mean age: 13.2 years) on these measures, pre- and post-treatment. Before treatment, ADHD-RS-IV (all ps0.05) and PSC scores (p0.05) were significantly higher and PedsQL™ scores (all ps0.05) significantly lower in the RLS group than in the control group. Eight and one of the RLS group had abnormally high PSC and ADHD-RS-IV scores, respectively. Following treatment, participants' daytime function had improved to levels similar to those of controls. Sixteen out of twenty-three cases were successfully treated primarily with iron supplement. Some children with RLS have daytime dysfunction; however, this can be treated with iron supplements.

In oral appliance therapy for obstructive sleep apnea (OSA), treatment success is arbitrarily defined. We investigated if the selection of response criteria affected the success rate of oral appliance treatment.The effects of an oral appliance on apnea-hypopnea index (AHI) and nadir percutaneous oxygen saturation (SpO2) were investigated in 224 OSA patients. Treatment success was defined as a reduction in AHI to5 events per hour with a50% reduction in baseline AHI (criterion 1), a follow-up AHI of10 events per hour with a50% reduction in baseline AHI (criterion 2), a50% reduction in baseline AHI alone (criterion 3), or a50% reduction in baseline AHI with the nadir SpO2 above 90% (criterion 4).The baseline AHI was reduced with an oral appliance in place compared with the follow-up value (23 ± 11-8.5 ± 8.7 events/h; P.05) in all of the participants. In every OSA subgroup, the success rate under criterion 3 (75% [mild], 71% [moderate], and 70% [severe]) was greater than that under criterion 1 (53%, 40%, and 24%, respectively). However, responders under criterion 3 in the severe OSA subgroup were still hypoxemic with a nadir SpO2 of 87 ± 8% even after treatment. This situation was improved by the use of criterion 4, in which a satisfactory improvement in AHI (from 38 ± 11 to 1 ± 1 events/h; P.01) was associated with a sufficient increase in the nadir SpO2 (93 ± 2%).We conclude that the selection of response criteria influences the success rate of oral appliance treatment. To avoid adverse health outcomes, an adjunct definition of treatment success using SpO2 may be effective for patients who have more severe OSA.

Parkinson's disease (PD) patients frequently develop obstructive sleep apnea (OSA). In order to clarify the clinical significance of OSA in PD, we compared descriptive variables between PD patients with OSA (PD+OSA) and without (PD-OSA), and between the PD+OSA group and a group of OSA patients without PD (control OSA). The apnea hypopnea index (AHI) cutoff of 15 episodes/hour on polysomnogram (PSG) was used to assign 107 PD patients to groups; OSA-related symptoms and PSG findings were then compared. Demographic and PSG variables were compared between PD+OSA patients and 31 OSA controls. Twenty-four patients with PD (22.4%) were classified as PD+OSA. There were no significant differences in descriptive variables between the PD+OSA and PD-OSA groups. The PD+OSA group had a higher arousal index on PSG than the PD-OSA group, although the two groups had similar ESS scores. The PD+OSA patients had a lower respiratory arousal index and a smaller decrease in oxygen saturation than the control OSA group, despite having a similar AHI. The prevalence of OSA in PD did not differ from that in the general elderly population, indicating that the clinical significance of OSA as a contributor to daytime sleepiness in PD is low.

The aim of this study was to develop and validate a Japanese version of the Athens Insomnia Scale (AIS-J).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.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.The AIS-J has sufficient validity and diagnostic utility.

Morbidity due to obstructive sleep apnea syndrome (OSAS) is increased in the elderly population. However, the clinical characteristics of OSAS in elderly patients have not been characterized conclusively. The aim of this study was to clarify differences in clinical characteristics of OSAS between patients with middle-age onset and elderly onset of OSAS.Patients with OSAS agedor = 65 years were classified into groups according to age at first identification of respiratory pauses during sleep: a middle-age onset group (n = 32) where onset was at age50 years and an elderly onset group (n = 31) where onset was at ageor = 60 years. We compared demographic variables; polysomnographic variables; daytime sleepiness measures, including the multiple sleep latency test (MSLT) and the Epworth sleepiness scale (ESS); and adequate level of nasal continuous positive airway pressure (CPAP) between groups.BMI and frequency of underlying cardiovascular disorder were lower in the elderly onset group than in the middle-age onset group. No significant differences in apnea-hypopnea index or percentage of the period showing O(2) desaturation were seen between groups. However, arousal index, maximal negative esophageal pressure value, and adequate nasal CPAP level were significantly smaller in the elderly onset group. Mean sleep latency on MSLT was longer, and ESS score was lower in the elderly onset group.Compared with the middle-age onset group, the clinical significance of OSAS in the elderly onset group seemed to remain milder. This finding is possibly because of the smaller physiologic response to respiratory events.

Patients with less severe obstructive sleep apnoea (OSA) are usually prescribed oral appliances and/or smaller optimal nasal continuous positive airway pressure (P(nCPAP)) in nCPAP therapy. We hypothesised that OSA patients with greater P(nCPAP) would not respond favourably to oral appliances. Oral appliances were inserted in nCPAP users after washing-out the nCPAP effect. Follow-up polysomnography was undertaken with the adjusted oral appliance in place. The predictability of P(nCPAP) was evaluated with receiver-operating characteristic (ROC) curves. The median baseline apnoea/hypopnoea index (AHI) was reduced with the oral appliance from 36 to 12 events.h(-1) in 35 patients. When responders were defined as patients showing a follow-up AHI of5 events.h(-1) with50% reduction in baseline AHI, the area under the ROC curve for P(nCPAP) was 0.76. The best cut-off value of P(nCPAP) turned out to be 10.5 cmH(2)O with a high negative predictive value (0.93) and a low negative likelihood ratio (0.18). OSA patients with a P(nCPAP) of10.5 cmH( 2)O are unlikely to respond to oral appliance therapy. This prediction is clinically helpful to both OSA patients and medical personnel in discussing oral appliances as a temporary substitute and/or alternative for nCPAP.

Background REM sleep behavior disorder (RBD) is a parasomnia characterized by intermittent loss of normal skeletal muscle atonia during REM sleep and elaborate motor activity associated with dream mentation. Idiopathic RBD (iRBD) has a known association with neurodegenerative diseases such as synucleinopathies. Recently, a specific screening scale for assessment of REM sleep behavior disorder (RBDSQ) was validated. Detection of RBD using a Japanese version of the RBDSQ would be useful in the stepwise diagnostic process. We investigated the validity and reliability of a Japanese version of this instrument, the RBDSQ-J. Methods Subjects were 52 patients with iRBD diagnosed according to criteria in the International Classification of sleep disorders, second edition, 55 obstructive sleep apnea syndrome (OSAS) patients who responded well to CPAP therapy after a diagnosis of RBD was ruled out by history and polysomnography (PSG) and 65 healthy subjects. Results An RBDSQ-J score cut-off of 5.0 was considered useful for differentiating the iRBD group from the healthy subjects or the OSAS group. Cronbach’s alpha for the entire RBDSQ-J was 0.866. Conclusion The RBDSQ-J had high sensitivity, specificity, and reliability and would be applicable as a screening method for iRBD in the elderly Japanese population.

A new, stereospecific synthesis of β-mannosides from glucose-derived 1,2-orthoesters has been developed by a simple four step procedure, comprising β-specific glycosidation of the 1,2-orthoesters, 2'-O-deacetylation, 2'-O-triflation, and SN 2 type inversion of the triflyl group providing β-D-Man-(1→6)-D-Gal,and β-D-Man-(1→4)-D-Glc derivatives in reasonable yield.

Introduction Oral appliance is generally accepted to be less efficacious than nasal continuous positive airway pressure (nCPAP) for the treatment of Obstructive Sleep Apnea (OSA). However, it was hypothesized that oral appliance was as efficacious as nCPAP when positional-dependent OSA (pOSA) patients were targeted. Materials and methods The gender (male), Body Mass Index (BMI) (20 Results There was no significant difference in the baseline AHI between oral appliance patients (20.92 ± 4.34) and nCPAP subjects (22.84 ± 2.65). The AHI was lowered significantly with oral appliance in place (16.05 ± 6.44, p p Conclusion These findings suggest that oral appliances are as efficacious as nCPAP in the treatment for patient with positional-dependent OSA. This information is available in discussing treatment of choice for OSA patients.