Validation of sleep-staging accuracy for an in-home sleep electroencephalography device compared with simultaneous polysomnography in patients with obstructive sleep apnea.

Efforts to simplify standard polysomnography (PSG) in laboratories, especially for obstructive sleep apnea (OSA), and assess its agreement with portable electroencephalogram (EEG) devices are limited. We aimed to evaluate the agreement between a portable EEG device and type I PSG in patients with OSA and examine the EEG-based arousal index's ability to estimate apnea severity. We enrolled 77 Japanese patients with OSA who underwent simultaneous type I PSG and portable EEG monitoring. Combining pulse rate, oxygen saturation (SpO2), and EEG improved sleep staging accuracy. Bland-Altman plots, paired t-tests, and receiver operating characteristics curves were used to assess agreement and screening accuracy. Significant small biases were observed for total sleep time, sleep latency, awakening after falling asleep, sleep efficiency, N1, N2, and N3 rates, arousal index, and apnea indexes. All variables showed > 95% agreement in the Bland-Altman analysis, with interclass correlation coefficients of 0.761-0.982, indicating high inter-instrument validity. The EEG-based arousal index demonstrated sufficient power for screening AHI ≥ 15 and ≥ 30 and yielded promising results in predicting apnea severity. Portable EEG device showed strong agreement with type I PSG in patients with OSA. These suggest that patients with OSA may assess their condition at home.

Association between electroencephalogram-based sleep characteristics and physical health in the general adult population.

We examined the associations between electroencephalogram (EEG)-based sleep characteristics and physical health parameters in general adults via a cross-sectional study recruiting 100 volunteers aged 30-59 years. Sleep characteristics were measured at home using a portable multichannel electroencephalography recorder. Using the k-means + + clustering method, according to 10 EEG-based parameters, participants were grouped into better (n = 39), middle (n = 46), and worse (n = 15) sleep groups. Comparing 50 physical health parameters among the groups, we identified four signals of difference (P < 0.05), including systolic (sBP) and diastolic blood pressure (dBP), γ-glutamyl transpeptidase (γ-GTP), and serum creatinine, where sBP reached a Bonferroni-corrected threshold (P < 0.001). The sBP was higher by 7.9 (95% confidence interval 1.9-13.9) and 15.7 (7.3-24.0) mmHg before adjustment and 5.4 (- 0.1-10.9) and 8.7 (1.1-16.3) mmHg after adjustment for age, sex, body mass index, smoking, drinking habits, and 3% oxygen desaturation index in the middle and worse sleep groups, respectively, than in the better group. As another approach, among 500 combinations of EEG-based and physical health parameters, there were 45 signals of correlation, of which 4 (N1% and sBP, dBP, γ-GTP, and triglycerides) reached a Bonferroni-corrected threshold (P < 0.0001). Thus, EEG-based sleep characteristics are associated with several physical health parameters, particularly sBP.

Characteristics of hypersomnia due to inflammatory demyelinating diseases of the central nervous system.

Background: Neuromyelitis optica spectrum disorder (NMOSD) diagnostic criteria for inflammatory demyelinating central nervous system diseases included symptomatic narcolepsy; however, no relevant case-control studies exist. We aimed to examine the relationship among cerebrospinal fluid orexin-A (CSF-OX) levels, cataplexy and diencephalic syndrome; determine risk factors for low-and-intermediate CSF-OX levels (≤200 pg/mL) and quantify hypothalamic intensity using MRI. Methods: This ancillary retrospective case-control study included 50 patients with hypersomnia and 68 controls (among 3000 patients) from Akita University, the University of Tsukuba and community hospitals (200 facilities). Outcomes were CSF-OX level and MRI hypothalamus-to-caudate-nucleus-intensity ratio. Risk factors were age, sex, hypersomnolence and MRI hypothalamus-to-caudate-nucleus-intensity ratio >130%. Logistic regression was performed for the association between the risk factors and CSF-OX levels ≤200 pg/mL. Results: The hypersomnia group (n=50) had significantly more cases of NMOSD (p<0.001), diencephalic syndrome (p=0.006), corticosteroid use (p=0.011), hypothalamic lesions (p<0.023) and early treatment (p<0.001). No cataplexy occurred. In the hypersomnia group, the median CSF-OX level was 160.5 (IQR 108.4-236.5) pg/mL and median MRI hypothalamus-to-caudate-nucleus-intensity ratio was 127.6% (IQR 115.3-149.1). Significant risk factors were hypersomnolence (adjusted OR (AOR) 6.95; 95% CI 2.64 to 18.29; p<0.001) and MRI hypothalamus-to-caudate-nucleus-intensity ratio >130% (AOR 6.33; 95% CI 1.18 to 34.09; p=0.032). The latter was less sensitive in predicting CSF-OX levels ≤200 pg/mL. Cases with MRI hypothalamus-to-caudate-nucleus-intensity ratio >130% had a higher rate of diencephalic syndrome (p<0.001, V=0.59). Conclusions: Considering orexin as reflected by CSF-OX levels and MRI hypothalamus-to-caudate-nucleus-intensity ratio may help diagnose hypersomnia with diencephalic syndrome.

Determination of optimal 25-hydroxyvitamin D cutoff values for the evaluation of restless legs syndrome among pregnant women.

STUDY OBJECTIVES: Vitamin D deficiency is associated with restless legs syndrome (RLS). However, a cutoff value for serum 25-hydroxyvitamin D (25[OH]D) level associated with RLS has yet to be clearly determined. We evaluated the association between 25(OH)D and RLS in pregnant women. METHODS: Data from 203 pregnant women were evaluated using blood samples taken in the third trimester. Liquid chromatography-tandem mass spectrometry and ligand binding assays were used to measure 25(OH)D. RLS was diagnosed based on International Classification of Sleep Disorders, third edition, criteria. The cutoff value for serum 25(OH)D associated with RLS was explored using receiver operating characteristic (ROC) curve and classification and regression tree (CART) analyses. RESULTS: The results of liquid chromatography-tandem mass spectrometry (x) and ligand binding assays (y) for serum 25(OH)D in the RLS (n = 35, 17.2%) and non-RLS (n = 168) groups showed a relationship of y = -2.65 + 0.08x . The RLS group showed lower serum 25(OH)D and folate levels. ROC curve and CART analyses revealed cutoff values of 10-12.7 ng/mL and 6.6-7.2 ng/mL for 25(OH)D and folate, respectively. Of the 5 women with RLS symptoms persisting at a moderate-to-severe level after delivery, 4 had 25(OH)D levels < 10 ng/mL and all had folate levels < 6 ng/mL. CONCLUSIONS: Vitamin D and folate deficiency were associated with RLS in pregnant women and may be associated with persistent moderate-to-severe postpartum RLS symptomatology; it is essential to examine associations with RLS while accounting for measurement methods and assay systems. CITATION: Miyazaki A, Takahashi M, Shuo T, Eto H, Kondo H. Determination of optimal 25-hydroxyvitamin D cutoff values for the evaluation of restless legs syndrome among pregnant women. J Clin Sleep Med. 2023;19(1):73-83.

The impact of sleep-wake problems on health-related quality of life among Japanese nursing college students: a cross sectional survey.

AIM: This study was conducted to examine the impact of sleep-wake problems on health-related quality of life of Japanese nursing college students.  METHODS: This cross-sectional study was conducted in 2019 on 150 third and fourth-year nursing college students from two locations in Japan. Insomnia severity was assessed using the Insomnia Severity Index (ISI) and health-related quality of life using the SF-8 questionnaire. The total sleep time (TST) was divided into 3 groups: < 6 h, 6-7 h (reference), and ≥ 7 h. The total ISI score was divided into 2 groups: ≥ 8 points and < 8 points (reference). Logistic regression analysis was performed to evaluate sleep-wake problems related to decline in mental health. RESULTS: The median mental health indicated in the SF-8 questionnaire was divided into two groups, and the factors causing decline in mental health were investigated. The odds ratios (95% confidence interval) for adjusted ISI ≥ 8 and TST on weekdays < 6 h was 6.51 (2.96-14.30) and 3.38 (1.40-8.17), respectively. Mental health status was significantly lower when ISI ≥ 8 and even lower when TST < 6 h. CONCLUSION: Insomnia and short sleep duration are associated with decreased mental health status in nursing college students. Many tended to lack sleep on weekdays. Sleep-wake problems identified while in university should be comprehensively dealt with.

A rare genetic variant in the cleavage site of prepro-orexin is associated with idiopathic hypersomnia.

Idiopathic hypersomnia (IH) is a rare, heterogeneous sleep disorder characterized by excessive daytime sleepiness. In contrast to narcolepsy type 1, which is a well-defined type of central disorders of hypersomnolence, the etiology of IH is poorly understood. No susceptibility loci associated with IH have been clearly identified, despite the tendency for familial aggregation of IH. We performed a variation screening of the prepro-orexin/hypocretin and orexin receptors genes and an association study for IH in a Japanese population, with replication (598 patients and 9826 controls). We identified a rare missense variant (g.42184347T>C; p.Lys68Arg; rs537376938) in the cleavage site of prepro-orexin that was associated with IH (minor allele frequency of 1.67% in cases versus 0.32% in controls, P = 2.7 × 10-8, odds ratio = 5.36). Two forms of orexin (orexin-A and -B) are generated from cleavage of one precursor peptide, prepro-orexin. The difference in cleavage efficiency between wild-type (Gly-Lys-Arg; GKR) and mutant (Gly-Arg-Arg; GRR) peptides was examined by assays using proprotein convertase subtilisin/kexin (PCSK) type 1 and PCSK type 2. In both PCSK1 and PCSK2 assays, the cleavage efficiency of the mutant peptide was lower than that of the wild-type peptide. We also confirmed that the prepro-orexin peptides themselves transmitted less signaling through orexin receptors than mature orexin-A and orexin-B peptides. These results indicate that a subgroup of IH is associated with decreased orexin signaling, which is believed to be a hallmark of narcolepsy type 1.

Genome-wide association study of idiopathic hypersomnia in a Japanese population.

Idiopathic hypersomnia (IH) is a rare sleep disorder characterized by excessive daytime sleepiness, great difficulty upon awakening, and prolonged sleep time. In contrast to narcolepsy type 1, which is a well-recognized hypersomnia, the etiology of IH remains poorly understood. No susceptibility loci for IH have been identified, although familial aggregations have been observed among patients with IH. Narcolepsy type 1 is strongly associated with human leukocyte antigen (HLA)-DQB1*06:02; however, no significant associations between IH and HLA alleles have been reported. To identify genetic variants that affect susceptibility to IH, we performed a genome-wide association study (GWAS) and two replication studies involving a total of 414 Japanese patients with IH and 6587 healthy Japanese individuals. A meta-analysis of the three studies found no single-nucleotide polymorphisms (SNPs) that reached the genome-wide significance level. However, we identified several candidate SNPs for IH. For instance, a common genetic variant (rs2250870) within an intron of PDE9A was suggestively associated with IH. rs2250870 was significantly associated with expression levels of PDE9A in not only whole blood but also brain tissues. The leading SNP in the PDE9A region was the same in associations with both IH and PDE9A expression. PDE9A is a potential target in the treatment of several brain diseases, such as depression, schizophrenia, and Alzheimer's disease. It will be necessary to examine whether PDE9A inhibitors that have demonstrated effects on neurophysiologic and cognitive function can contribute to the development of new treatments for IH, as higher expression levels of PDE9A were observed with regard to the risk allele of rs2250870. The present study constitutes the first GWAS of genetic variants associated with IH. A larger replication study will be required to confirm these associations. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-021-00349-2.

A novel quantitative evaluation of deposits adhered to worn orthokeratology contact lenses.

PURPOSE: Total deposition and deposition along the reverse curve of heavily deposited worn orthokeratology (OK) lenses were quantitatively evaluated using two novel imaging methods. In addition, the cleaning efficacies of a contact lens cleaning solution for daily use and an intensive cleaner and protein remover solution were evaluated using the same two methods. STUDY DESIGN: Experimental study. METHODS: Twenty-six worn reverse-geometry OK lenses (MY Emerald, Technopia) were photographed for use in three experiments: (1) total deposition was assessed before and after cleaning with two cleaning solutions; (2) in addition to assessing total lens deposition, the feasibility of measuring the thickness of lens deposits along the reverse curve was assessed; and (3) after confirming it was possible to assess the thickness of lens deposits, the thickness of deposits was assessed before and after cleaning with a daily contact lens cleaning solution (O2 Care®, Menicon Co., Ltd.) and an intensive cleaner and protein remover (Progent®, Menicon Co., Ltd.). Total lens deposition was assessed as the total volume of cloudiness over the lens surface in terms of volume per unit pixel. Cross-sectional images were taken from worn OK lenses to assess the thickness of lens deposits on the reverse curve as the area of deposits/horizontal length. RESULTS: Significant differences in total deposition were found between the three cleaning conditions for the twenty worn OK lenses (mean total deposition ± SD for pre-cleaning = 0.209 ± 0.076; post-daily cleaning = 0.124 ± 0.078; and post-intensive cleaning = 0.045 ± 0.046) (p < 0.001). Mean total deposition and thickness of the deposits along the reverse curve for the three lenses from the second experiment were 0.310 and 6.0 mm, respectively. The mean thicknesses of lens deposits found in the third experiment under the 3 conditions were as follows: pre-cleaning = 3.4 µm; post-daily cleaning = 2.3 µm; and post-intensive cleaning = 0.0 µm. CONCLUSION: The two novel imaging methods used in this study detected significant amounts of deposits attached to worn OK lenses and were sensitive enough to detect a reduction in deposition following the use of the two cleaning solutions tested. Furthermore, these methods could visualize and quantify the thickness of lens deposits along the reverse curve.

Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis.

Dysfunction of the circadian clock has been implicated in the pathogenesis of cardiovascular disease. The CLOCK protein is a core molecular component of the circadian oscillator, so that mice with a mutated Clock gene (Clk/Clk) exhibit abnormal rhythms in numerous physiological processes. However, here we report that chronic kidney disease (CKD)-induced cardiac inflammation and fibrosis are attenuated in Clk/Clk mice even though they have high blood pressure and increased serum angiotensin II levels. A search for the underlying cause of the attenuation of heart disorder in Clk/Clk mice with 5/6 nephrectomy (5/6Nx) led to identification of the monocytic expression of G protein-coupled receptor 68 (GPR68) as a risk factor of CKD-induced inflammation and fibrosis of heart. 5/6Nx induces the expression of GPR68 in circulating monocytes via altered CLOCK activation by increasing serum levels of retinol and its binding protein (RBP4). The high-GPR68-expressing monocytes have increased potential for producing inflammatory cytokines, and their cardiac infiltration under CKD conditions exacerbates inflammation and fibrosis of heart. Serum retinol and RBP4 levels in CKD patients are also sufficient to induce the expression of GPR68 in human monocytes. Our present study reveals an uncovered role of monocytic clock genes in CKD-induced heart failure.

False-positive cases in multiple sleep latency test by accumulated sleep debt.

PURPOSE: Multiple sleep latency test (MSLT) is performed as objective assessment of sleepiness, on the following day after polysomnography (PSG). In most clinics, patients are required to stay for 2 days. However, if patients have chronic sleep debt before the examination, even if they get adequate nocturnal sleep during the initial PSG, their sleep debt would not be fully resolved, affecting MSLT results. This may lead to improper administration of psycho-stimulant medication. To clarify the sleep debt for the patients who showed short sleep latencies, we compared the mean sleep latencies of MSLTs. METHODS: Twelve hypersomnolent males, who underwent MSLTs (1st MSLT with 1 night and 2nd MSLT with more than 3 nights), were enrolled. We selected these cases based on the longer total sleep time on PSG night compared to the mean total sleep time on pre-examination sleep logs and shortened sleep latencies on PSG. To evaluate the effect of the sleep debt for the patients who showed short sleep latencies, we extended their hospitalization or re-hospitalized them. RESULTS: The mean sleep latency of 1st MSLT was 5.8 minutes and that of 2nd was 13.9 minutes (P < .001). Among these 12 cases, 5 cases altered from short to normal sleep latencies at the 2nd MSLT. These 5 cases were prevented from over-diagnoses by the extension of evaluations. CONCLUSIONS: The sleep debt may produce false-positive results when patients are examined by standard PSG and MSLT. Accumulation of sleep debt will cause shortened sleep latencies in the following nights. Patients should be advised to extend their hospitalization before PSG and MSLT to reduce the chronic sleep debt for accurate diagnosis of hypersomnia.

Sarcopenia is associated with insomnia in Japanese older adults: a cross-sectional study of data from the Nagasaki Islands study.

BACKGROUND: Sarcopenia is associated with increased mortality among older adults. Sleep-related problems have been studied as factors related to sarcopenia. This study was conducted to determine the relationship between sleep-related problems and sarcopenia among Japanese community-dwelling older adults using data from the Nagasaki Islands Study. METHODS: This cross-sectional study analyzed data collected from 2017 to 2018. A total of 1592 older adults (575 men, 36.1%) aged 65 years or older participated. Sarcopenia was evaluated using the skeletal muscle mass index and grasp powers based on the criteria of the Asian Working Group for Sarcopenia. Odds ratios for sarcopenia were calculated using logistic regression analysis. Furthermore, subgroup analysis was performed based on the following tertiles of age: 65-70 years, 71-78 years, and 79-98 years. RESULTS: The number of participants with sarcopenia was 238 (14.9%). The median age of participants in the sarcopenia group (80 years; interquartile range: 74-84) was significantly higher than in the non-sarcopenia group (73 years; interquartile range 69-79; P <  0.001). In the sarcopenia group, 70.9% of participants had difficulty initiating and/or maintaining sleep, sleep duration tended to be longer (P <  0.001), and 33.3% of participants' sleep duration was over 9 h. In a logistic regression analysis for sarcopenia, advancing age was the most prominent factor, and the adjusted odds ratio (95% confidence interval) of facing difficulty initiating and/or maintaining sleep was 1.60 (1.14-2.25). Despite longer sleep duration being a significant factor in the univariable analysis, it was not significant in the multivariable analysis. In the logistic regression analysis for sarcopenia among older adults aged 79-98 years, the odds ratio (95% confidence interval) among women was significantly low at 0.53 (0.33-0.83). CONCLUSIONS: Sarcopenia is associated with difficulty initiating and/or maintaining sleep among Japanese older adults. In sarcopenia control measures, sleep/wake disorders related to insomnia are required to be evaluated in detail to help inform nursing and medical policy.

Interleukin-18 and fibroblast growth factor 2 in combination is a useful diagnostic biomarker to distinguish adult-onset Still's disease from sepsis.

OBJECTIVE: To identify potential biomarkers to distinguish adult-onset Still's disease (AOSD) from sepsis. METHOD: We recruited 70 patients diagnosed with AOSD according to the Yamaguchi criteria, 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the AOSD and sepsis groups in order to identify specific molecular networks. Further, multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by their importance and determine specific biomarkers for distinguishing AOSD from sepsis. RESULTS: Seventeen of the 40 cytokines were found to be suitable for further analyses. The serum levels of eleven were significantly higher in patients with AOSD than healthy controls. Levels of serum fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and interleukin (IL)-18 were significantly elevated in patients with AOSD compared with those with sepsis, and cytokine clustering patterns differed between these two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both FGF-2 and IL-18 could distinguish AOSD from sepsis with high accuracy (cutoff value for FGF-2 = 36 pg/mL; IL-18 = 543 pg/mL, sensitivity 100%, specificity 72.2%, accuracy 93.8%). CONCLUSION: Determination of FGF-2 and IL-18 levels in combination may represent a biomarker for the differential diagnosis of AOSD from sepsis, based on the measurement of multiple cytokines.

The prevalence of insomnia and restless legs syndrome among Japanese outpatients with rheumatic disease: A cross-sectional study.

The prevalence of symptomatic insomnia and the prevalence of restless legs syndrome (RLS) are known to be higher among patients with rheumatic diseases compared to the general population. The prevalences of insomnia and RLS reported in a questionnaire by Japanese patients with rheumatic diseases at an outpatient clinic were analyzed herein. The association between the patients' disease activity and their sleep quality was analyzed. Of 121 rheumatic disease patients, 70 were enrolled. The median (interquartile range) age at enrollment was 62.0 (47.8-68.0) years. There were 58 women (82.9%) and 12 men (17.1%), and 43 patients (61.4%) with rheumatoid arthritis (RA), nine (12.9%) with systemic lupus erythematosus (SLE), and 18 (25.7%) with other rheumatic diseases. Twenty patients (28.6%) had one or more moderate-to-severe insomnia symptoms, and 10 (14.3%) were diagnosed with RLS. Among the patients with RA, the swollen joint count based on a 28-joint assessment (SJC28) was significantly higher in the insomnia group (n = 13) compared to the non-insomnia group (n = 30) (p = 0.006). A classification and regression tree (CART) analysis showed that the cut-off points of ≥3 mg/day prednisolone (PSL) treatment and <16.54% as the transferrin saturation (TSAT) value would best predict RLS in rheumatic disease. Patients with rheumatic disease had a high prevalence of symptomatic insomnia and RLS. A higher dose of PSL and lower TSAT were associated with the occurrence of RLS.

Characteristics of sleep/wake problems and delivery outcomes among pregnant Japanese women without gestational complications.

BACKGROUND: Frequently observed sleep/wake problems among pregnant women need comprehensive evaluation. This study was conducted to clarify the sleep/wake problems among pregnant women without gestational complications during the second and third trimester and the effects of sleep/wake problems on delivery outcomes. METHODS: A total of 88 Japanese pregnant women participated in this study. In their second and third trimester, subjective sleep quality, insomnia severity, excessive daytime sleepiness (EDS), and restless legs syndrome/Willis-Ekbom disease (RLS/WED) were assessed using questionnaires; also, sleep disordered breathing (SDB) was screened using a pulse oximeter. RESULTS: From the second to the third trimester, an increasing tendency of sleep/wake problems was observed. During the third trimester, the percentages of women experiencing decreased subjective sleep quality, difficulty maintaining sleep (DMS), EDS, RLS/WED, and 3% oxygen desaturation index (ODI) values ≥5/h were 62.5, 45.5, 48.9, 9.1, and 29.5%, respectively. In a logistic regression analysis for EDS in the third trimester, the adjusted odds ratio (95% confidence interval) of total sleep duration < 6 h, moderate to severe DMS, and 3% ODI values ≥5/h were 3.25 (1.16-9.10), 4.74 (1.60-14.00), and 0.90 (0.28-2.89), respectively. Although short sleep durations, decreased subjective sleep quality, EDS, and SDB did not affect delivery outcomes or the infant's condition, the percentage of women undergoing cesarean sections in the severe insomnia group was significantly higher (p = 0.008). CONCLUSIONS: Sleep/wake problems were frequent during pregnancy, especially during the third trimester. EDS among pregnant women was associated with shorter sleep durations and DMS rather than SDB. The effect of factors related to insomnia on delivery outcomes should thus be considered a crucial problem among pregnant Japanese women without gestational complications in clinical practice.

Reticulocyte levels have an ambivalent association with hypertension and atherosclerosis in the elderly: a cross-sectional study.

Purpose: Age-related reduction in bone marrow activity has been shown to cause anemia, and hypertension and endothelial dysfunction (atherosclerosis) are age-related diseases. However, recent studies have revealed a close association between bone marrow activity and endothelial maintenance. This study aimed to determine the association between elevated reticulocyte levels in conjunction with vigorous bone marrow activity and hypertension and atherosclerosis among the elderly. Study population and Methods: To determine the associations between reticulocyte levels and hypertension and atherosclerosis, we conducted a cross-sectional study of 2,098 elderly Japanese individuals, aged between 60 and 89 years, who had participated in an annual health check-up in 2014. Results: Of the total study population, 1,348 individuals were diagnosed with hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg and/or having used antihypertensive medication), and 393 were diagnosed with atherosclerosis (carotid intima-media thickness ≥1.1 mm). Reticulocyte levels were found to be significantly positively associated with hypertension and inversely associated with atherosclerosis. Cardiovascular risk factor-adjusted odds ratios and 95% confidence intervals for hypertension and atherosclerosis, when raised incrementally by 1 standard deviation to determine reticulocyte levels (5.5×104 cells/µL for men and 5.0×104 cells/µL for women), were 1.12 (1.01, 1.25) and 0.83 (0.72, 0.94), respectively. Conclusion: Along with established cardiovascular risk factors, reticulocyte levels in elderly Japanese individuals were found to be positively associated with hypertension and inversely associated with atherosclerosis. This finding may help clarify the background mechanisms concerning the association between bone marrow activity and vascular remodeling.

The impact of rotating work schedules, chronotype, and restless legs syndrome/Willis-Ekbom disease on sleep quality among female hospital nurses and midwives: A cross-sectional survey.

BACKGROUND: Decreases in subjective sleep quality are prevalent among nurses and midwives engaged in rotating shift work. OBJECTIVES: The present study aimed to examine the relationship between differences in work schedules and subjective sleep quality among female nursing staff. DESIGN: A cross-sectional survey design was used for descriptive and logistic regression analyses. Data collection was conducted from December 2016 to September 2017. SETTINGS: Participants were recruited from five regional core hospitals in Japan. PARTICIPANTS: A total of 1253 nurses and midwives were included in the final analysis. METHODS: Subjective sleep quality was assessed using the Japanese version of the Pittsburgh Sleep Quality Index. Chronotype and social jet lag were calculated for both work day and work-free day. Symptoms related to restless legs syndrome/Willis-Ekbom disease were assessed using the Japanese version of the Cambridge-Hopkins questionnaire short form 13. Participants with the urge to move their legs, though not fulfilling the restless legs syndrome/Willis-Ekbom disease criteria, were classified as having leg motor restlessness. Logistic regression analyses for poor sleep were adjusted for age, body mass index, smoking, drinking, menstruation status, the presence of premenstrual syndrome, and the presence of a spouse. RESULTS: Rates of poor sleep (Pittsburgh Sleep Quality Index score ≥6) among those working, day shifts, rotating 12.5 hour night shifts, rotating 16 hour night shifts, and three-shift rotations were 41.2%, 51.1%, 44.5%, and 60.4%, respectively. Approximately 40% of three-shift rotation workers experienced difficulty initiating sleep. Shift workers tended to exhibit evening chronotype, delayed sleep phase, and high social jet lag. The prevalence of restless legs syndrome/Willis-Ekbom disease was 2.5%. Leg motor restlessness was observed in. 15.5% of participants. The adjusted odds ratios (95% confidence interval) of three-shift work (vs. day shift), evening chronotype (vs. morning chronotype), and the presence of leg motor restlessness (vs. no leg motor restlessness) for those with poor sleep were 2.20 (1.47-3.30), 1.95 (1.29-2.94), and 1.66 (1.15-2.39), respectively. CONCLUSIONS: Regardless of the working schedules, rates of poor sleep were high among female hospital nurses and midwives. Our findings suggest that poor sleep quality is influenced by three-shift rotation, the evening chronotype, and leg motor restlessness.

Cardio-ankle vascular index and circulating CD34-positive cell levels as indicators of endothelial repair activity in older Japanese men.

AIM: The cardio-ankle vascular index (CAVI) reflects functional arterial stiffness, which is related to endothelial dysfunction. CD34-positive cells carry out an important function in endothelial repair. However, there have been no reports assessing the association between CAVI and the number of circulating CD34-positive cells. METHODS: We carried out a cross-sectional study of 249 Japanese men, aged 60-69 years, who underwent annual health checkups between 2013 and 2015. As individuals with high levels of circulating CD34-positive cells might indicate the influence of consumptive reduction of circulating CD34-positive cells as a result of aggressive endothelial repair, participants were stratified by circulating CD34-positive cell levels, using the median value in this population (0.95 cells/µL) as the cut-off. RESULTS: For participants with low circulating CD34-positive cell levels, logarithmic values of circulating CD34-positive cells were inversely associated with CAVI (multivariable standardized parameter estimate [ß] = -0.22, P = 0.014), but not for participants with high levels (ß = -0.04, P = 0.638). In addition, even when no significant associations between CAVI and carotid intima-media thickness were detected for participants with low circulating CD34-positive cell levels (ß = -0.02, P = 0.865), significant positive associations were identified for participants with high levels (ß = 0.22, P = 0.028). CONCLUSIONS: As circulating CD34-positive cell count might indicate endothelial repair activity, the present results show that CAVI is affected by insufficient endothelial repair in individuals with low circulating CD34-positive cell counts. Our results also show that a positive association between CAVI and carotid intima-media thickness exists only in individuals with aggressive endothelial repair, which indicates the presence of organic arterial disease, such as atherosclerosis. Geriatr Gerontol Int 2019; 19: 557-562.

Association between chronic kidney disease and carotid intima-media thickness in relation to circulating CD34-positive cell count among community-dwelling elderly Japanese men.

BACKGROUND AND AIMS: Endothelial injury is well-known as a process that can lead to chronic kidney disease (CKD) and atherosclerosis. Hematopoietic activity is known to be associated inversely with CKD and positively with atherosclerosis. Since bone-derived progenitor cells (CD34-positive cells) contribute to endothelial repair (including the progression of atherosclerosis), understanding the association between CKD and carotid intima-media thickness (CIMT), in relation to circulating CD34-positive cell count, may be an efficient means of clarifying the mechanisms underlying endothelial activity. METHODS: We conducted a cross-sectional study of 570 elderly Japanese men aged 60-69 years, who underwent a general health check-up. Participants were stratified as per a median circulating CD34-positive cell count (1.01 cells/µL). RESULTS: Independent of the known cardiovascular risk factors, CIMT was found to be positively associated with CKD in the participants with high circulating CD34-positive cell counts but not in participants with low counts. Odds ratios were 1.40 (1.04, 1.89) for participants with high and 1.01 (0.72, 1.43) for participants with low circulating CD34-positive cell counts after adjustment for known cardiovascular risk factors at 95% confidence intervals for CKD with one standard deviation increment of CIMT. CONCLUSIONS: A positive association between CIMT and CKD was observed among participants with high circulating CD34-positive cell counts but not among participants with low counts. Endothelial repair activity might determine the association between CKD and CIMT.

A variant at 9q34.11 is associated with HLA-DQB1*06:02 negative essential hypersomnia.

Essential hypersomnia (EHS) is a lifelong disorder characterized by excessive daytime sleepiness without cataplexy. EHS is associated with human leukocyte antigen (HLA)-DQB1*06:02, similar to narcolepsy with cataplexy (narcolepsy). Previous studies suggest that DQB1*06:02-positive and -negative EHS are different in terms of their clinical features and follow different pathological pathways. DQB1*06:02-positive EHS and narcolepsy share the same susceptibility genes. In the present study, we report a genome-wide association study with replication for DQB1*06:02-negative EHS (408 patients and 2247 healthy controls, all Japanese). One single-nucleotide polymorphism, rs10988217, which is located 15-kb upstream of carnitine O-acetyltransferase (CRAT), was significantly associated with DQB1*06:02-negative EHS (P = 7.5 × 10-9, odds ratio = 2.63). The risk allele of the disease-associated SNP was correlated with higher expression levels of CRAT in various tissues and cell types, including brain tissue. In addition, the risk allele was associated with levels of succinylcarnitine (P = 1.4 × 10-18) in human blood. The leading SNP in this region was the same in associations with both DQB1*06:02-negative EHS and succinylcarnitine levels. The results suggest that DQB1*06:02-negative EHS may be associated with an underlying dysfunction in energy metabolic pathways.