Dream-enactment behaviours during the COVID-19 pandemic: an international COVID-19 sleep study.

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.

Urine cell image recognition using a deep-learning model for an automated slide evaluation system.

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.

A Cross-Sectional Study of Evening Hyperphagia and Nocturnal Ingestion: Core Constituents of Night Eating Syndrome with Different Background Factors.

This web-based cross-sectional survey aimed to elucidate the differences between the two core symptoms of night eating syndrome (NES): evening hyperphagia and nocturnal ingestion in the general Japanese population aged 16-79 years. Participants who consumed at least 25% of daily calories after dinner were defined as having evening hyperphagia. Those who consumed food after sleep initiation at least twice a week were determined to have nocturnal ingestion. Of the 8348 participants, 119 (1.5%) were categorized in the evening hyperphagia group, 208 (2.6%) in the nocturnal ingestion group, and 8024 in the non-NES group. Participants with evening hyperphagia and nocturnal ingestion had significantly higher anxiety scores (p < 0.05 and p < 0.001, respectively) and depression (p < 0.001 for both) than those without NES. Multiple logistic regression analysis revealed that evening hyperphagia was significantly and independently associated with higher body mass index, shorter sleep duration, later sleep-wake schedule, and higher insomnia score, while nocturnal ingestion was significantly and independently associated with younger age, smoking habit, living alone, earlier sleep-wake schedule, and higher insomnia score. Sleep duration and sleep-wake schedule characteristics in the two groups were opposite, suggesting differences in the sleep pathophysiology mechanisms.

Current state of hypnotic use disorders: Results of a survey using the Japanese version of Benzodiazepine Dependence Self-Report Questionnaire.

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.

Prevalence and Associated Factors of Nocturnal Eating Behavior and Sleep-Related Eating Disorder-Like Behavior in Japanese Young Adults: Results of an Internet Survey Using Munich Parasomnia Screening.

Nocturnal (night) eating syndrome and sleep-related eating disorder have common characteristics, but are considered to differ in their level of consciousness during eating behavior and recallability. To date, there have been no large population-based studies determining their similarities and differences. We conducted a cross-sectional web-based survey for Japanese young adults aged 19-25 years to identify factors associated with nocturnal eating behavior and sleep-related eating disorder-like behavior using Munich Parasomnia Screening and logistic regression. Of the 3347 participants, 160 (4.8%) reported experiencing nocturnal eating behavior and 73 (2.2%) reported experiencing sleep-related eating disorder-like behavior. Smoking (p < 0.05), use of hypnotic medications (p < 0.01), and previous and/or current sleepwalking (p < 0.001) were associated with both nocturnal eating behavior and sleep-related eating disorder-like behavior. A delayed sleep-wake schedule (p < 0.05) and sleep disturbance (p < 0.01) were associated with nocturnal eating behavior but not with sleep-related eating disorder-like behavior. Both nocturnal eating behavior and sleep-related eating disorder-like behavior had features consistent with eating disorders or parasomnias. Nocturnal eating behavior but not sleep-related eating disorder-like behavior was characterized by a sleep-awake phase delay, perhaps representing an underlying pathophysiology of nocturnal eating syndrome.

Phase II study of vinorelbine plus carboplatin with concurrent radiotherapy in elderly patients with non-small cell lung cancer.

OBJECTIVE: Concurrent chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer. In the current aging society, the establishment of an ideal treatment strategy for locally advanced non-small cell lung cancer in the elderly is warranted. To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. PURPOSE: To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. METHODS: This multicenter, phase II study included patients with physiologically or medically unresectable stage I-III NSCLC, who were ≥70 years old. The patients received carboplatin (AUC 2) and vinorelbine (15 mg/m2) both on day 1, 8, 22 and 29 concurrently with radiotherapy (2.0 Gy/day, 30 fractions, total 60 Gy). The primary endpoint was the objective response rate. The secondary endpoints were the progression-free survival, overall survival and the incidence of adverse events. RESULTS: 50 patients were accrued (42 men and 8 women). The median age was 77 years (range, 70-89 years) and the clinical stage was I/II/III in 3/7/40, respectively. Forty-seven patients completed the planned treatment. The response was complete remission in 4, partial response in 31, stable disease in 12 and progressive disease in 3, giving an objective response rate of 70% (95% confidence interval: 55.4-82.1). Frequent high Grade 3 or higher adverse events were hematologic, but no treatment deaths were noted. The median and 2-year progression-free survival were 8.4 months and 21.1% (95% confidence interval: 9.5-32.7%), respectively, and the median and 2-year overall survival were 15.4 months and 41.1% (95% confidence interval: 27.0-55.2), respectively. CONCLUSION: Concurrent chemoradiotherapy with carboplatin and vinorelbine showed an acceptable objective response rate and safety in elderly patients.

Efficacy and safety of cefditoren pivoxil for exacerbations of chronic obstructive pulmonary disease: A prospective multicenter interventional study.

Oral antibiotic therapy for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves an aminopenicillin with clavulanic acid, a macrolide, or a quinolone. To date, however, the clinical efficacy and safety of the oral cephalosporin cefditoren pivoxil has not been evaluated in Japanese patients with acute exacerbations of COPD. We conducted a prospective, multicenter, single arm, interventional study from January 2013 to March 2017 to determine the efficacy and safety of oral administration of 200 mg cefditoren pivoxil three times daily for 7 days in a cohort of 29 eligible patients from 15 hospitals. The mean age (SD) of participants was 73.1 (8.1) years and 28 had a smoking history (the mean [SD] of smoking index, 1426.7 [931.7]). The primary efficacy endpoint was clinical response (cure rate) at test of cure, which was set at 5-10 days after treatment ceased. Of the 23 patients finally analyzed, cure was achieved in 15 (65.2%), while 8 (34.8%) remained uncured. Previous experience of acute exacerbations significantly affected the cure rate: none of the three patients who had at least two prior exacerbations were cured, while 15 of the 20 patients with one or fewer prior exacerbations were cured (p = 0.032). The microbiological eradication rate was 88.9% at test of cure. During treatment, mild pneumonia was reported as an adverse event in one patient (3.4%) but resolved within 10 days of onset. We conclude that cefditoren pivoxil represents a viable alternative for antibiotic therapy in patients with few prior exacerbations.

Alkali-soluble pectin suppresses IgE production in human myeloma cell line in vitro.

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.

Ability of suvorexant to prevent delirium in patients in the intensive care unit: a randomized controlled trial.

AIM: There are no effective, tolerable, and established medications for preventing delirium in critically ill patients admitted to the intensive care unit (ICU). We investigated whether suvorexant was effective in preventing ICU delirium. METHODS: This randomized controlled study evaluated 70 adult patients (age ≥20 years) admitted to the mixed medical ICU of the Tokyo Medical University Hospital (Tokyo, Japan) between May 2015 and February 2017. Patients were randomized using a sealed envelope method to receive either suvorexant (n = 34; 15 mg for elderly patients and 20 mg for younger adults) or conventional treatment (n = 36) for a 7-day period. The primary outcome was delirium incidence based on the definition in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders. RESULTS: No significant between-group differences were observed in the demographic or clinical characteristics. Kaplan-Meier estimates revealed that time to delirium onset was significantly longer in the suvorexant group than in the conventional group (P < 0.05). CONCLUSION: Suvorexant might be effective in preventing delirium in ICU patients.

Validation of a sheet-shaped body vibrometer for screening of obstructive sleep apnea.

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.

Prevalence, symptomatic features, and factors associated with sleep disturbance/insomnia in Japanese patients with type-2 diabetes.

PURPOSE: To clarify the prevalence and symptomatic characteristics of sleep disturbance/insomnia among type-2 diabetes mellitus (DM) Japanese patients. METHODS: A cross-sectional survey of Japanese patients with the disorder was conducted. Participants consisted of 622 type-2 DM patients (mean 56.1±9.56 years) and 622 sex- and age-matched controls. Participants' scores in the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J), the Japanese version of the 12-item Center for Epidemiologic Studies Depression Scale (CES-D), the Medical Outcomes Study 8-item Short Form Health Survey (SF-8), and the glycated hemoglobin A1c (HbA1c) of type-2 DM patients were analyzed. RESULTS: There were 253 poor sleepers (43.9%) in the type-2 DM group as a result of dichotomization with the PSQI-J cutoff total score of 5.5. The type-2 DM group recorded a higher mean PSQI-J total score (P<0.01) and manifested poorer sleep maintenance. Poor sleepers in both groups had lower mental component summary from SF-8 (MCS), physical component summary from SF-8 (PCS), and CES-D than good sleepers, and good sleepers in both groups had higher MCS, PCS, and CES-D than poor sleepers. Higher body mass index, presence of smoking habit, and living alone were significantly associated with sleep disturbance/insomnia symptoms, but HbA1c was not associated with sleep disturbance/insomnia in the type-2 DM group. CONCLUSION: Individuals affected with type-2 DM are likely to experience sleep problems, characterized by disturbance in sleep maintenance. Sleep disturbance/insomnia symptoms in DM patients might considerably reduce health-related quality of life.

WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice.

The with-no-lysine kinase (WNK) 4 gene is a causative gene in pseudohypoaldosteronism type II. Although WNKs are widely expressed in the body, neither their metabolic functions nor their extrarenal role is clear. In this study, we found that WNK4 was expressed in mouse adipose tissue and 3T3-L1 adipocytes. In mouse primary preadipocytes and in 3T3-L1 adipocytes, WNK4 was markedly induced in the early phase of adipocyte differentiation. WNK4 expression preceded the expression of key transcriptional factors PPARγ and C/EBPα. WNK4-siRNA-transfected 3T3-L1 cells and human mesenchymal stem cells showed reduced expression of PPARγ and C/EBPα and lipid accumulation. WNK4 protein affected the DNA-binding ability of C/EBPß and thereby reduced PPARγ expression. In the WNK4-/- mice, PPARγ and C/EBPα expression were decreased in adipose tissues, and the mice exhibited partial resistance to high-fat diet-induced adiposity. These data suggest that WNK4 may be a proadipogenic factor, and offer insights into the relationship between WNKs and energy metabolism.

Later sleep schedule and depressive symptoms are associated with usage of multiple kinds of hypnotics.

OBJECTIVE: Usage of high doses of hypnotics possibly causes various adverse events. However, the risk factors of using multiple kinds of hypnotics have been inconclusive. To clarify this, we conducted a web-based cross-sectional questionnaire survey on the Japanese adult population. METHODS: A cross-sectional Internet-linked survey was conducted on 10,016 individuals and 1030 participants (10.3%) having subjective insomnia proceeded to subsequent analyses. The analyzed subjects were categorized into non-users of hypnotics (n = 833; 80.9%), users of a single kind of hypnotic (n = 96; 9.3%), and users of multiple kinds of hypnotics (n = 101; 9.8%). The descriptive variables including demographic data, scores of Center for Epidemiological Studies Depression Scale (CES-D), Short Form-8 Health-Related Quality of Life [QOL (SF-8)], Pittsburgh Sleep Quality Index (PSQI), and other parameters were compared among the groups. RESULTS: The users of multiple kinds of hypnotics had the highest mean score of CES-D, the lowest mental component summary of QOL (SF-8), and the latest sleep schedule among the three groups (p < 0.001). Logistic regression analyses revealed that sex (female: OR = 2.38; p < 0.001) and age (≥43 years old: OR = 2.61; p < 0.001) were independently associated with use of a single kind of hypnotic, while later sleep schedule (midpoint of sleep ≥5:30 a.m.: OR = 2.26; p < 0.001) and higher CES-D score (≥16 points: OR = 2.41; p < 0.001) were independently associated with use of multiple kinds of hypnotics. CONCLUSIONS: Characteristics of users of multiple kinds of hypnotics were different from those of users of a single kind of hypnotic.

Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3.

Mutations in with-no-lysine kinase (WNK) 1, WNK4, Kelch-like 3 (KLHL3), and Cullin3 result in an inherited hypertensive disease, pseudohypoaldosteronism type II. WNK activates the Na-Cl cotransporter (NCC), increasing sodium reabsorption in the kidney. Further, KLHL3, an adapter protein of Cullin3-based E3 ubiquitin ligase, has been recently found to bind to WNK, thereby degrading them. Insulin and vasopressin have been identified as powerful activators of WNK signaling. In this study, we investigated effects of Akt and PKA, key downstream substrates of insulin and vasopressin signaling, respectively, on KLHL3. Mass spectrometry analysis revealed that KLHL3 phosphorylation at S433. Phospho-specific antibody demonstrated defective binding between phosphorylated KLHL3 and WNK4. Consistent with the fact that S433 is a component of Akt and PKA phosphorylation motifs, in vitro kinase assay demonstrated that Akt and PKA can phosphorylate KLHL3 at S433, that was previously reported to be phosphorylated by PKC. Further, forskolin, a representative PKA stimulator, increased phosphorylation of KLHL3 at S433 and WNK4 protein expression in HEK293 cells by inhibiting the KLHL3 effect that leads to WNK4 degradation. Insulin also increased phosphorylation of KLHL3 at S433 in cultured cells. In conclusion, we found that Akt and PKA phosphorylated KLHL3 at S433, and phosphorylation of KLHL3 by PKA inhibited WNK4 degradation. This could be a novel mechanism on how insulin and vasopressin physiologically activate the WNK signal.

Dynein arms are strain-dependent direction-switching force generators.

Dynein is a minus-end-directed motor that can generate (forward) force to move along the microtubule toward its minus end. In addition, axonemal dyneins were reported to oscillate in the generation of forward force, and cytoplasmic dynein is observed to generate bidirectional forces in response to defined chemical states. Both dyneins can also respond to mechanically applied force. To test whether axonemal dynein can switch direction of force generation, we measured force using an optical trap and UV-photolysis of caged ATP. We observed that isolated dynein could repeatedly generate force in both directions along the microtubule. Bidirectional force was also observed for dynein arms that are still attached on the doublet microtubules. Axonemal dynein generated force to move backward (∼ 4 pN) as well as forward (5-6 pN) along microtubules. Furthermore, backward force could be stimulated by plus-end directed external force applied to axonemal dynein before ATP application. The results show that axonemal dynein is unique exhibiting multiple modes of force generation including backward and forward force, oscillatory force and slow, repetitive bidirectional force. The results also demonstrate that mechanical strain is important for switching the directionality of force generation in axonemal dyneins.

Giant Acceleration of Diffusion Observed in a Single-Molecule Experiment on F(1)-ATPase.

The giant acceleration (GA) of diffusion is a universal phenomenon predicted by the theoretical analysis given by Reimann et al. [Phys. Rev. Lett. 87, 010602 (2001)]. Here we apply the theory of the GA of diffusion to a single-molecule experiment on a rotary motor protein, F(1), which is a component of F(o)F(1) adenosine triphosphate synthase. We discuss the energetic properties of F(1) and identify a high energy barrier of the rotary potential to be 20k(B)T, with the condition that the adenosine diphosphates are tightly bound to the F(1) catalytic sites. To conclude, the GA of diffusion is useful for measuring energy barriers in nonequilibrium and single-molecule experiments.

[A Girl with Intraorbital Varix: A Case Report].

We report a case of intraorbital varix. A 16-year-old girl showed sudden left-sided exophthalmos after vomiting. After several episodes of vomiting, she developed complete loss of vision in the left eye, followed by orbital pain, disruption of eye movement, and periorbital swelling. No change in symptoms or signs was observed after the Valsalva maneuver or jugular vein compression. Computed tomography (CT), magnetic resonance imaging (MRI), and angiography were inconclusive. Transcranial surgery revealed a large varix near the optic nerve. The lesion could not be completely resected because the orbital fat interfered with its complete visualization. We cauterized the lesion to reduce its volume. The patient's symptoms improved markedly after surgery and cauterization. Thus, cauterization appears to be an effective strategy to reduce the volume of an unresectable intraorbital varix.

Practical 3DCT imaging of the vestibular aqueduct for Meniere's disease.

CONCLUSION: Radiographic visualization of the vestibular aqueduct (VA) from a lateral inside view was effective in assessing patients with Meniere's disease (MD). There were no VA shapes specific to MD on radiography, except for an obliterated VA. This technique could yield more accurate images and functional assessment of the VA for MD evaluation in a clinically useful and convenient manner, without requiring morphologic measurement. OBJECTIVE: To visualize the detailed images of the VA using three-dimensional (3D) computed tomography (CT) and discuss its clinical utility in assessing MD. SUBJECTS AND METHODS: The VAs in 13 healthy subjects and 25 MD patients, who were definitely diagnosed according to criteria described by the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology, Head and Neck Surgery (AAO-HNS), were imaged from the medial and lateral sides using 3DCT and compared to conventional CT images. RESULTS: Examination of the VA from both the lateral outside and inside views on 3DCT yielded more precise images than generated by conventional CT and could be useful to estimate the VA function. The estimated VA function in the MD ears was significantly abnormal compared to the function in healthy ears. An obliterated VA was characteristic of affected MD ears.

Impact of hypnotics use on daytime function and factors associated with usage by female shift work nurses.

OBJECTIVE: We investigated quality of life (QOL) and work performance of hypnotics users, and explored the factors associated with multiple hypnotics usage in shift work nurses. METHODS: We conducted a questionnaire-based, cross-sectional survey on nurses in university hospitals. We analyzed responses from 1202 nurses; 997 were female shift work nurses (82.9%), including 696 and 281 two- and three-shift workers, respectively. RESULTS: The rate of hypnotics use was 10% (6.9% were single hypnotic users and 3.1% were multiple hypnotics users). The rate of insomnia did not differ between the single and multiple hypnotics users. However, multiple hypnotics users showed lower QOL, more severe depressive symptoms, and greater frequencies of work-related errors than those using a single hypnotic. A multiple logistic regression analysis revealed that age ≥27 years, presence of depression, eveningness chronotype, and presence of insomnia symptoms were significantly associated with hypnotics use. On the other hand, only the existence of shift work disorder (SWD) was significantly associated with usage of multiple hypnotics. CONCLUSIONS: The present study suggested that usage of multiple hypnotics is not beneficial for relieving insomnia or for keeping better QOL in shift work nurses. It would be desirable to explore the causal relationship between SWD and multiple hypnotics use in a future longitudinal study.

Single carbon nanotube-based reversible regulation of biological motor activity.

Because of their small size and high thermal conductivity, carbon nanotubes (CNTs) are excellent candidates for exploring heat transfer at the level of individual molecules in biological research. With a view toward examining the thermal regulation of single biomolecules, we here developed single CNTs as a new platform for observing the motile activity of myosin motors. On multiwall CNTs (diameter ∼170 nm; length ∼10 µm) coated with skeletal-muscle myosin, the ATP-driven sliding of single actin filaments was clearly observable. The normal sliding speed was ∼6 µm/s. Locally irradiating one end of the CNT with a red laser (642 nm), without directly irradiating the active myosin motors, accelerated the sliding speed to ∼12 µm/s, indicating the reversible activation of protein function on a single CNT in real time. The temperature along the CNT, which was estimated from the temperature-dependence of the sliding speed, decreased with the distance from the irradiated spot. Using these results with the finite element method, we calculated a first estimation of the thermal conductivity of multiwall CNTs in solution, as 1540 ± 260 (Wm(-1) K(-1)), which is consistent with the value estimated from the width dependency of multiwall CNTs and the length dependency of single-wall CNTs in a vacuum or air. The temporal regulation of local temperature through individual CNTs should be broadly applicable to the selective activation of various biomolecules in vitro and in vivo.