Outdoor daylight exposure and longer sleep promote wellbeing under COVID-19 mandated restrictions.

Light is an important regulator of daily human physiology in providing time-of-day information for the circadian clock to stay synchronised with the 24-hr day. The coronavirus disease 2019 (COVID-19) pandemic led to social restrictions in many countries to prevent virus spreading, restrictions that dramatically altered daily routines and limited outdoor daylight exposure. We previously reported that sleep duration increased, social jetlag decreased, and mid-sleep times delayed during social restrictions (Global Chrono Corona Survey, N = 7,517). In the present study, we investigated in the same dataset changes in wellbeing and their link to outdoor daylight exposure, and sleep-wake behaviour. In social restrictions, median values of sleep quality, quality of life, physical activity and productivity deteriorated, while screen time increased, and outdoor daylight exposure was reduced by ~58%. Yet, many survey participants also reported no changes or even improvements. Larger reductions in outdoor daylight exposure were linked to deteriorations in wellbeing and delayed mid-sleep times. Notably, sleep duration was not associated with outdoor daylight exposure loss. Longer sleep and decreased alarm-clock use dose-dependently correlated with changes in sleep quality and quality of life. Regression analysis for each wellbeing aspect showed that a model with six predictors including both levels and their deltas of outdoor daylight exposure, sleep duration and mid-sleep timing explained 5%-10% of the variance in changes of wellbeing scores (except for productivity). As exposure to daylight may extenuate the negative effects of social restriction and prevent sleep disruption, public strategies during pandemics should actively foster spending more daytime outdoors.

Structural Insights into HIV-1 Vif-APOBEC3F Interaction.

UNLABELLED: The HIV-1 Vif protein inactivates the cellular antiviral cytidine deaminase APOBEC3F (A3F) in virus-infected cells by specifically targeting it for proteasomal degradation. Several studies identified Vif sequence motifs involved in A3F interaction, whereas a Vif-binding A3F interface was proposed based on our analysis of highly similar APOBEC3C (A3C). However, the structural mechanism of specific Vif-A3F recognition is still poorly understood. Here we report structural features of interaction interfaces for both HIV-1 Vif and A3F molecules. Alanine-scanning analysis of Vif revealed that six residues located within the conserved Vif F1-, F2-, and F3-box motifs are essential for both A3C and A3F degradation, and an additional four residues are uniquely required for A3F degradation. Modeling of the Vif structure on an HIV-1 Vif crystal structure revealed that three discontinuous flexible loops of Vif F1-, F2-, and F3-box motifs sterically cluster to form a flexible A3F interaction interface, which represents hydrophobic and positively charged surfaces. We found that the basic Vif interface patch (R17, E171, and R173) involved in the interactions with A3C and A3F differs. Furthermore, our crystal structure determination and extensive mutational analysis of the A3F C-terminal domain demonstrated that the A3F interface includes a unique acidic stretch (L291, A292, R293, and E324) crucial for Vif interaction, suggesting additional electrostatic complementarity to the Vif interface compared with the A3C interface. Taken together, these findings provide structural insights into the A3F-Vif interaction mechanism, which will provide an important basis for development of novel anti-HIV-1 drugs using cellular cytidine deaminases. IMPORTANCE: HIV-1 Vif targets cellular antiviral APOBEC3F (A3F) enzyme for degradation. However, the details on the structural mechanism for specific A3F recognition remain unclear. This study reports structural features of interaction interfaces for both HIV-1 Vif and A3F molecules. Three discontinuous sequence motifs of Vif, F1, F2, and F3 boxes, assemble to form an A3F interaction interface. In addition, we determined a crystal structure of the wild-type A3F C-terminal domain responsible for the Vif interaction. These results demonstrated that both electrostatic and hydrophobic interactions are the key force driving Vif-A3F binding and that the Vif-A3F interfaces are larger than the Vif-A3C interfaces. These findings will allow us to determine the configurations of the Vif-A3F complex and to construct a structural model of the complex, which will provide an important basis for inhibitor development.

Numerical simulation of blood flow in femoral perfusion: comparison between side-armed femoral artery perfusion and direct femoral artery perfusion.

Computational numerical analysis was performed to elucidate the flow dynamics of femoral artery perfusion. Numerical simulation of blood flow was performed from the right femoral artery in an aortic model. An incompressible Navier-Stokes equation and continuity equation were solved using computed flow dynamics software. Three different perfusion models were analyzed: a 4.0-mm cannula (outer diameter 15 French size), a 5.2-mm cannula (18 French size) and an 8-mm prosthetic graft. The cannula was inserted parallel to the femoral artery, while the graft was anastomosed perpendicular to the femoral artery. Shear stress was highest with the 4-mm cannula (172 Pa) followed by the graft (127 Pa) and the 5.2-mm cannula (99 Pa). The cannula exit velocity was high, even when the 5.2-mm cannula was used. Although side-armed perfusion with an 8-mm graft generated a high shear stress area near the point of anastomosis, flow velocity at the external iliac artery was decreased. The jet speed decreased due to the Coanda effect caused by the recirculation behind sudden expansion of diameter, and the flow velocity maintains a constant speed after the reattachment length of the flow. This study showed that iliac artery shear stress was lower with the 5.2-mm cannula than with the 4-mm cannula when used for femoral perfusion. Side-armed graft perfusion generates a high shear stress area around the anastomotic site, but flow velocity in the iliac artery is slower in the graft model than in the 5.2-mm cannula model.

Sleepiness induced by sleep-debt enhanced amygdala activity for subliminal signals of fear.

BACKGROUND: Emotional information is frequently processed below the level of consciousness, where subcortical regions of the brain are thought to play an important role. In the absence of conscious visual experience, patients with visual cortex damage discriminate the valence of emotional expression. Even in healthy individuals, a subliminal mechanism can be utilized to compensate for a functional decline in visual cognition of various causes such as strong sleepiness. In this study, sleep deprivation was simulated in healthy individuals to investigate functional alterations in the subliminal processing of emotional information caused by reduced conscious visual cognition and attention due to an increase in subjective sleepiness. Fourteen healthy adult men participated in a within-subject crossover study consisting of a 5-day session of sleep debt (SD, 4-h sleep) and a 5-day session of sleep control (SC, 8-h sleep). On the last day of each session, participants performed an emotional face-viewing task that included backward masking of nonconscious presentations during magnetic resonance scanning. RESULTS: Finally, data from eleven participants who were unaware of nonconscious face presentations were analyzed. In fear contrasts, subjective sleepiness was significantly positively correlated with activity in the amygdala, ventromedial prefrontal cortex, hippocampus, and insular cortex, and was significantly negatively correlated with the secondary and tertiary visual areas and the fusiform face area. In fear-neutral contrasts, subjective sleepiness was significantly positively correlated with activity of the bilateral amygdala. Further, changes in subjective sleepiness (the difference between the SC and SD sessions) were correlated with both changes in amygdala activity and functional connectivity between the amygdala and superior colliculus in response to subliminal fearful faces. CONCLUSION: Sleepiness induced functional decline in the brain areas involved in conscious visual cognition of facial expressions, but also enhanced subliminal emotional processing via superior colliculus as represented by activity in the amygdala. These findings suggest that an evolutionally old and auxiliary subliminal hazard perception system is activated as a compensatory mechanism when conscious visual cognition is impaired. In addition, enhancement of subliminal emotional processing might cause involuntary emotional instability during sleep debt through changes in emotional response to or emotional evaluation of external stimuli.

Investigation of macro and micro sleep structures of first night effect in school-aged children.

This study aimed to investigate the occurrence and age-related changes of the first night effect (FNE) in school-age children using both macro (sleep architecture) and micro (frequency analysis) structures to polysomnography (PSG) data. PSG data from two consecutive nights were obtained from 38 healthy children aged 6-15 years. Sleep variables and power spectral analysis were compared between the two nights. The relationship between age and the difference in sleep variables and power values between the two nights was examined using correlation analysis. The first night showed significant reductions in total sleep time, sleep efficiency, N1, N2, and REM sleep, as well as significant increases in sleep onset latency and wake after sleep onset. The decrease in N3 and the increase in N2 due to FNE were positively and negatively correlated with age, respectively. Spectral analysis showed no effect of FNE for most variables, but there was a trend toward an increase in the convergence value of the δ band with age. FNE occurs in school-age children, and its manifestation changes with age. The decrease in N3 and increase in N2 become more pronounced with age, while the enhancement of low-frequency power is consistent across ages. These findings highlight the importance of considering age and specific sleep indicators when interpreting pediatric PSG results and underscore the need for a multi-level approach to understanding sleep changes across development.

The Japanese version of the reduced morningness-eveningness questionnaire.

Circadian typology, or "morningness" and "eveningness," is generally assessed using the Morningness-Eveningness Questionnaire (MEQ), a 19-item scale that could be burdensome in large-scale surveys. To overcome this, a 5-item version known as the reduced morningness-eveningness questionnaire (rMEQ), which is sensitive to the assessment of circadian typology, was developed; however, a validated Japanese version of the rMEQ is yet to be established. This study aimed to develop and validate the Japanese version of the rMEQ. Five essential items for the rMEQ were selected from existing Japanese MEQ data (N = 2,213), and the rMEQ was compiled. We conducted a confirmatory factor analysis for the psychometric properties of the rMEQ and confirmed its robust one-factor structure for evaluating morningness-eveningness (GFI = 0.984, AGFI = 0.951, CFI = 0.935, and RMSEA = 0.091). Reliability was evaluated via internal consistency of rMEQ items using Cronbach's α and McDonald's ω, and the values were 0.618 and 0.654, respectively. The rMEQ scores strongly correlated with MEQ (ρ = 0.883, p < 0.001), and classification agreement (Morning, Neither, and Evening types) between rMEQ and MEQ was 77.6% (Cramer's V = 0.643, Weighted Cohen's κ = 0.72), confirming the validity. The Japanese rMEQ may be a valuable tool for the efficient assessment of circadian typologies.

Sleep patterns in Metropolitan and Regional areas in Japan: Before and during COVID-19 social restrictions.

Sleep timing is an important output of the circadian system. The COVID-19-mandated social restrictions significantly altered commuting time and sleep duration regionally in Japan. This study aimed to elucidate sleep patterns, especially chronotype and social jetlag (SJL), due to changes in social time pressure through the social restrictions between the Metropolitan and Regional areas in Japan. As part of the Global Chrono Corona Survey 2020 (GCCS), the data were collected during social restrictions (SR), but pre-COVID-19 behaviours were also queried retrospectively. We analyzed a cohort of 729 respondents representing both the Metropolitan and the Regional areas separately for workdays and work-free days. While the areas showed no difference in SJL before SR, the differential decrease was larger in the Metropolitan area during SR, resulting in a significant difference in SJL between the areas. The outdoor light exposure before SR was 30 min longer in the Metropolitan areas than in the Regional; during SR both areas showed similarly low (below 1 h) outdoor light exposures. The variables associated with decreased SJL were the Metropolitan areas, work-from-home, a no-usage alarm clock on workdays, and chronotypes (mid-sleep time on free days corrected for sleep deficit accumulated over the workweek, MSFsc) during SR. The results suggest that relaxed social schedules, as reflected in the increased frequency of work-from-home and reduced alarm clock use, and moving towards earlier MSFsc during SR were linked to decreased SJL and were more prominent in the Metropolitan areas. This study provides insights into sleep patterns and the social time pressure markers, by comparison between residential groups in Japan.

Estimating dim light melatonin onset time in children using delta changes in melatonin.

We aimed to establish a method for estimating dim light melatonin onset (DLMO) using mathematical slopes calculated from melatonin concentrations at three sampling points before and after sleep in children. The saliva of 30 children (mean age ± SD: 10.2 ± 1.3 years old) was collected under dim-light conditions up to six times every hour starting at 17:30 (t17), namely, 18:30 (t18), 19:30 (t19), 20:30 (t20), 21:30 (t21), 22:30 (t22), and 23:30 (t23), in the evening, and at 6:00 (t30) the following morning. We calculated SLOPEon (mathematical slope between melatonin concentrations at t18 and t20, t21 or t22), SLOPEoff (the slope between t20, t21 or t22, and t30), and ΔSLOPE, which is generated by subtracting SLOPEon from SLOPEoff. DLMO was estimated by multiple regression analysis with the leave-one-out cross-validation (LOOCV) method using SLOPEon and SLOPEoff, and ΔSLOPE. The intraclass correlation coefficient (ICC) between the estimated and measured DLMOs was used as the index of estimation accuracy. DLMOs estimated using multiple regression equations with SLOPEon and SLOPEoff yielded significant ICCs for the measured DLMOs, with the largest ICC at t20 (ICC = 0.634). Additionally, the ICC between the estimated and measured DLMOs using the equation with ΔSLOPE was significant, with a larger ICC at t20 (ICC = 0.726) than that of the equation with SLOPEon and SLOPEoff. Our results showed that DLMO could be estimated with a certain level of accuracy from salivary melatonin levels at three time points before and after sleep in children. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00493-x.

Association between sleep state misperception and bedtime behavior in patients with chronic insomnia.

Previous studies on sleep state misperception have objectively evaluated sleep status in special environments using polysomnography. There is a paucity of data from studies that evaluated habitual sleep status in home environments. The present study aimed to investigate sleep state misperception in the home environment of patients with chronic insomnia using a lumbar-worn actigraphy to identify sleep habits associated with sleep state misperception severity. Thirty-one patients and 42 healthy volunteers were included in the insomnia and non-insomnia group, respectively. Participants recorded subjective assessments in sleep diaries, objective assessments with an actigraphy worn for 14 days, and self-assessments using questionnaires. Both groups had similar objective sleep ratings; however, insomnia group had significantly worse subjective ratings (total sleep time, wake after sleep onset, and sleep onset latency). A significant correlation was found between subjective and objective total sleep time scores in non-insomnia group but not in insomnia group. Insomnia group had earlier bedtimes, significantly longer bedtimes, and impaired daytime functioning (Sheehan Disability Scale score); additionally, they underestimated their total sleep time, particularly with earlier bedtimes and longer laying durations. Monitoring the sleep status and habits of individuals in home environments could be instrumental in identifying key points for targeted interventions on sleep hygiene and cognitive behavioral therapy for insomnia.

Development and validation of the Japanese version of the Bedtime Procrastination Scale (BPS-J).

BACKGROUND: The average sleep duration of Japanese people is shorter than that of people from other countries, and bedtime procrastination is suspected to be one of the factors contributing to this issue. This study aimed to develop and validate the Japanese version of the Bedtime Procrastination Scale (BPS-J). METHODS: The BPS-J was developed through procedures including the translation and back-translation of the scale, cognitive interviews with 100 participants who reported having experiences of being diagnosed with insufficient sleep syndrome (ISS) or receiving treatment for ISS using open-ended online questionnaires, and expert checking. To investigate the scale's validity and reliability, an online survey was conducted with daytime workers aged 20 - 65 years without a history of sleep disorders other than ISS. Half the participants were retested using the same survey after 14 days. Participants' responses to the Brief Self-Control Scale (BSCS), General Procrastination Scale (GPS), and Munich ChronoType Questionnaire (MCTQ), and data on sleep-related variables such as sleep duration on workdays and the days per week of fatigue or sleep loss, sex, and age, were collected. RESULTS: We analyzed data from 574 participants to assess scale validity. We then analyzed data from 280 participants to determine test-retest reliability. Confirmatory factor analyses revealed that the two-factor model without Item 2 was most suitable for the BPS-J, unlike other language versions. Regardless of the full-item model or the model with Item 2 eliminated, sufficient reliability and significant correlations with the BSCS, GPS, MCTQ, and sleep-related variables such as sleep duration per night on work days, days per week of feeling fatigued, and days per week of sleep loss were observed. Logistic and linear regressions showed that the relationships between the BPS-J, sleep-related variables, and MCTQ were maintained after adjusting for sex and age. CONCLUSION: The BPS-J had sufficient validity and reliability. Further, eliminating Item 2 from the original version of the BPS strengthened the ability to survey Japanese daytime workers.

[Multifunctional HIV accessory proteins are hub proteins antagonizing host antiviral factors].

HIV has several accessory proteins (Vif, Vpu, Vpr, Vpx, and Nef) along with structural /enzymatic (Gag, Pol, and Env) and gene-expression regulatory proteins (Tat and Rev) essential for viral replication. The accessory proteins are neither required in some kinds of cells and nor all conserved between HIV-1 and HIV-2. For these reasons, their functional roles and mechanisms had been unclear. However, since a finding of Vif's neutralizing function against host restriction factor APOBEC3G, it has been elucidated that the accessory proteins play critical roles to antagonize host intrinsic antiviral activity. So far, in addition to Vif-APOBEC3, Vpu-BST-2/Tetherin and Vpx-SAMHD1 have been identified as such examples. Here, we summarize the biological functions and features on HIV accessory proteins in terms of antagonizing factors against the host antiviral factors.

Association between sleep duration and antibody acquisition after mRNA vaccination against SARS-CoV-2.

Introduction: Sleep enhances the antibody response to vaccination, but the relationship between sleep and mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not fully understood. Methods: In this prospective observational study, we investigated the influence of sleep habits on immune acquisition induced by mRNA vaccines against SARS-CoV-2 in 48 healthy adults (BNT-162b2, n=34; mRNA-1273, n=14; female, n=30, 62.5%; male, n=18, 37.5%; median age, 39.5 years; interquartile range, 33.0-44.0 years) from June 2021 to January 2022. The study measured sleep duration using actigraphy and sleep diaries, which covered the periods of the initial and booster vaccinations. Results: Multivariable linear regression analysis showed that actigraphy-measured objective sleep duration 3 and 7 days after the booster vaccination was independently and significantly correlated with higher antibody titers (B=0.003; 95% confidence interval, 0.000-0.005; Beta=0.337; p=0.02), even after controlling for covariates, including age, sex, the type of vaccine, and reactogenicity to the vaccination. Associations between acquired antibody titer and average objective sleep duration before vaccination, and any period of subjective sleep duration measured by sleep diary were negligible. Discussion: Longer objective, but not subjective, sleep duration after booster vaccination enhances antibody response. Hence, encouraging citizens to sleep longer after mRNA vaccination, especially after a booster dose, may increase protection against SARS-CoV-2. Study registration: This study is registered at the University Hospital Medical Information Network Center (UMIN: https://www.umin.ac.jp) on July 30, 2021, #UMIN000045009.

Rhythmic expression of circadian clock genes in human leukocytes and beard hair follicle cells.

Evaluating individual circadian rhythm traits is crucial for understanding the human biological clock system. The present study reports characterization of physiological and molecular parameters in 13 healthy male subjects under a constant routine condition, where interfering factors were kept to minimum. We measured hormonal secretion levels and examined temporal expression profiles of circadian clock genes in peripheral leukocytes and beard hair follicle cells. All 13 subjects had prominent daily rhythms in melatonin and cortisol secretion. Significant circadian rhythmicity was found for PER1 in 9 subjects, PER2 in 3 subjects, PER3 in all 13 subjects, and BMAL1 in 8 subjects in leukocytes. Additionally, significant circadian rhythmicity was found for PER1 in 5 of 8 subjects tested, PER2 in 2 subjects, PER3 in 6 subjects, and BMAL1 in 3 subjects in beard hair follicle cells. The phase of PER1 and PER3 rhythms in leukocytes correlated significantly with that of physiological rhythms. Our results demonstrate that leukocytes and beard hair follicle cells possess an endogenous circadian clock and suggest that PER1 and PER3 expression would be appropriate biomarkers and hair follicle cells could be a useful tissue source for the evaluation of biological clock traits in individuals.

Increased cerebral blood flow in the right frontal lobe area during sleep precedes self-awakening in humans.

BACKGROUND: Some people can subconsciously wake up naturally (self-awakening) at a desired/planned time without external time stimuli. However, the underlying mechanism regulating this ability remains to be elucidated. This study sought to examine the relationship between hemodynamic changes in oxyhemoglobin (oxy-Hb) level in the prefrontal cortex and sleep structures during sleep in subjects instructed to self-awaken. RESULTS: Fifteen healthy right-handed male volunteers with regular sleep habits participated in a consecutive two-night crossover study. The subjects were instructed to wake up at a specified time ("request" condition) or instructed to sleep until the morning but forced to wake up at 03:00 without prior notice ("surprise" condition). Those who awoke within ± 30 min of the planned waking time were defined as those who succeeded in self-awakening ("success" group). Seven subjects succeeded in self-awakening and eight failed.No significant differences were observed in the amounts of sleep in each stage between conditions or between groups. On the "request" night, an increase in oxy-Hb level in the right prefrontal cortex and a decrease in δ power were observed in the "success" group around 30 min before self-awakening, whereas no such changes were observed in the "failure" group. On the "surprise" night, no significant changes were observed in oxy-Hb level or δ power in either group. CONCLUSIONS: These findings demonstrate a correlation between self-awakening and a pre-awakening increase in hemodynamic activation in the right prefrontal cortex, suggesting the structure's contribution to time estimation ability.

Carryover effect on next-day sleepiness and psychomotor performance of nighttime administered antihistaminic drugs: a randomized controlled trial.

BACKGROUND: Antihistamines with strong sedative-hypnotic properties are frequently prescribed for insomnia secondary to allergy, but the potential risks of such administration have not been fully elucidated. SUBJECTS AND METHODS: This randomized, double-blind, placebo-controlled crossover study was conducted to evaluate next-day sleepiness and psychomotor performance following the administration of antihistamines. Twenty-two healthy male participants participated in four drug administration sessions with more than a 1-week interval between the sessions. Either zolpidem 10 mg, or diphenhydramine 50 mg, or ketotifen 1 mg, or a placebo was administered before sleep, and polysomnography was conducted to evaluate sleep. In the morning and afternoon of the day after administration, the participants were evaluated for subjective sleepiness, objective sleepiness, and psychomotor performance. RESULTS: The antihistamines with high blood-brain barrier-crossing efficiency were significantly associated with sleepiness and psychomotor performance decline the next day. Ketotifen showed the strongest carryover effect, followed by diphenhydramine. Compared with the placebo, no significant carryover effect was observed with zolpidem. CONCLUSION: The results suggest that the risk-benefit balance should be considered in the ready use of antihistamines that easily cross the blood-brain barrier for alleviating secondary insomnia associated with allergies.

Validity of an algorithm for determining sleep/wake states using FS-760 in school-aged children.

BACKGROUND: Actigraphy is a method used for determining sleep (S)/wakefulness (W) by actigraph, a device equipped with a built-in accelerometer and an algorithm validated for each device. The S/W determination algorithm for the waist-worn actigraph FS-760 has been formulated for adults. However, the algorithm for children has not been established. The purpose of this study was to formulate an algorithm for discriminating S/W in school-aged children using FS-760 and to evaluate its validity. We further tested the generalizability of existing algorithm for adults by applying it to the children's activity data and then examined factors associated with adult algorithm agreement rates by multiple regression analysis using combined adult and children data. METHODS: Sixty-five, healthy, school-aged children (aged 6 to 15 years) were recruited and randomly assigned to two groups: A (n = 33) and B (n = 32). They underwent 8-h polysomnography (PSG) and wore FS-760 simultaneously to obtain activity data. To determine the central epoch of the sleep/wake states (𝑥), a five-order linear discriminant analysis was conducted using the activity intensity of group A for five epochs (𝑥-2, 𝑥-1, 𝑥, 𝑥+1, 𝑥+2; 10 min) and evaluate its accuracy with the activity of group B. To reveal the factors associated with adult algorithm agreement rate, we integrated the activity, age, sleep efficiency of 15 adults (aged 20 to 39 years) and those of 65 children for multiple regression analysis. RESULTS: The mean agreement rate of the developed algorithm was 91.0%, with a mean sensitivity (true sleep detection rate) of 93.0% and a mean specificity (true wakefulness detection rate) of 63.9%. The agreement rate of the adult algorithm applied to children's activity was significantly lower (81.8%) than that of the children algorithm. Multiple regression analysis showed that the agreement rates calculated by the adult algorithm were significantly related to mean activity of the 𝑥 epoch in NREM and REM sleep as well as age and sleep efficiency. CONCLUSIONS: The S/W states in school-aged children can be reliably assessed using the developed algorithm for waist-worn actigraph FS-760. Since the accuracy of the adult algorithms decreased when applied it to children which have different activity levels during sleep, the establishment and validation of population-specific S/W algorithms should be required.

Circadian phase advances in children during camping life according to the natural light-dark cycle.

BACKGROUND: It is known that the circadian rhythm phase in adults can be advanced in a natural light-dark cycle without electrical lighting. However, the effect of advanced sleep-wake timing according to the natural light-dark cycle on children's circadian phase is unclear. We investigated the effects of approximately 2 weeks of camping life with little access to artificial lighting on children's circadian phases. We also conducted an exploratory examination on the effects of wake time according to natural sunrise time on the manner of the advance of their circadian phases. METHODS: Twenty-one healthy children (mean ± SD age, 10.6 ± 1.4 years) participated in a camping program with wake time (4:00) being earlier than sunrise time (EW condition), and 21 healthy children (10.4 ± 1.1 years) participated in a camping program with wake time (5:00) being almost matched to sunrise time (SW condition). Salivary dim light melatonin onset (DLMO) before the camping program and that after approximately 2 weeks of camping were compared. RESULTS: DLMO was advanced by approximately 2 h after the camping program compared with the circadian phase in daily life in both conditions. In addition, the advances in DLMO were significantly correlated with mid-sleep points before the camp in both conditions (EW: r = 0.72, p < 0.01, SW: r = 0.70, p < 0.01). These correlations mean that the phase advance was greater for the children with delayed sleep habits in daily life. Furthermore, in the EW condition, mean DLMO after the camp (18:09 ± 0:33 h) was earlier than natural sunset time and there was no significant decrease in interindividual variability in DLMO. On the other hand, in the SW condition, mean DLMO after the camp (18:43 ± 0:20 h) matched natural sunset time and interindividual variability in DLMO was significantly lower than that before the camp. CONCLUSIONS: Camping with advanced sleep and wake timing under natural sunlight advances children's circadian phases. However, DLMO earlier than sunset in an early waking condition may lead to large interindividual variability in the circadian rhythm phase.

Associations Between the 2011 Great East Japan Earthquake and Tsunami and the Sleep and Mental Health of Japanese People: A 3-Wave Repeated Survey.

PURPOSE: Large-scale natural disasters have an enormous physical and mental impact, immediately after they occur, on people living near the central disaster areas. It is known that, in the early stages, a seismic disaster triggers high rates of symptoms for insomnia, depression, and anxiety. However, little information is available about their medium- to long-term clinical outcomes. In this study, we conducted a repeated cross-sectional nationwide questionnaire survey to clarify changes in the prevalence of insomnia and its background factors after the Great East Japan Earthquake, a huge earthquake with a moment magnitude of 9.0 that occurred on March 11, 2011. METHODS: We conducted a repeated cross-sectional survey in November 2009 (pre-earthquake, 1224 participants), July 2011 (4 months post-earthquake, 1259 participants), and August 2012 (18 months post-earthquake, 1289 participants) using stratified random sampling from 157 Japanese sites. RESULTS: Compared to 2009, the prevalence of insomnia statistically increased nationwide immediately post-disaster (11.7% vs 21.2%; p < 0.001) but significantly decreased in 2012 compared to immediately after the earthquake (10.6% vs 21.2%; p < 0.001). In 2011, insomnia was most frequent in the central disaster area. Multivariable logistic regression models demonstrated the association between the following factors and increased risk of insomnia: being a woman (odds ratio [OR] 1.48, 95% confidence interval [CI]: 1.00-2.19), being employed in 2009 (OR 1.74, 95% CI: 1.15-2.62), and being of younger age group (20-64 years) in 2011 (OR 1.64, 95% CI: 1.12-2.42) and 2012 (OR 2.50 95% CI: 1.47-4.23). Post-earthquake, the prevalence of insomnia symptoms in men increased, while the gender difference decreased and was no longer statistically significant. Additionally, insomnia was associated with psychological distress (scores ≥5 on the Kessler Psychological Distress Scale) in 2011 and 2012. CONCLUSION: This study demonstrated that the prevalence of insomnia was significantly higher after the earthquake. Moreover, individuals with insomnia were more likely to experience psychological distress after the earthquake that continued until 2012.

Risk factors for low adherence to methylphenidate treatment in pediatric patients with attention-deficit/hyperactivity disorder.

Poor adherence is a major concern in the treatment of attention-deficit/hyperactivity disorder (ADHD). The objective of this study was to evaluate factors linked to early interruption of and low adherence to treatment with osmotic-release oral system methylphenidate hydrochloride (OROS-MPH) in pediatric patients with ADHD. A total of 1353 young people (age 6-17 years) with a diagnosis of ADHD who newly started OROS-MPH were extracted from the pharmacoepidemiological data of 3 million people in Japan. The cohort was retrospectively surveyed every month for 12 months. Ten possible risk factors were extracted from the data and analyzed by multivariable logistic regression. Sensitivity analysis was conducted to ensure the robustness of the analysis. The results revealed that treatment adherence was generally poor, with a tendency for discontinuation in the early stage. Multivariable logistic regression results showed that adherence is reduced by female sex, lower starting dose, and concomitant atomoxetine or hypnotics. These findings may help clinicians to predict the risk of poor adherence in the early stage of treatment and improve not only patients' symptoms, but also their quality of life.

The Role of the Thalamus in the Neurological Mechanism of Subjective Sleepiness: An fMRI Study.

PURPOSE: The thalamus, the region that forms the attentional network and transmits external sensory signals to the entire brain, is important for sleepiness. Herein, we examined the relationship between activity in the thalamus-seed brain network and subjective sleepiness. MATERIALS AND METHODS: Fifteen healthy male participants underwent an experiment comprising a baseline evaluation and two successive interventions, a 9-day sleep extension followed by 1-night total sleep deprivation. Pre- and post-intervention tests included the Karolinska sleepiness scale and neuroimaging for arterial spin labeling and functional connectivity. We examined the association between subjective sleepiness and the functional magnetic resonance imaging indices. RESULTS: The functional connectivity between the left or right thalamus and various brain regions displayed a significant negative association with subjective sleepiness, and the functional connectivity between the left and right thalamus displayed a significant positive association with subjective sleepiness. The graph theory analysis indicated that the number of positive functional connectivity related to the thalamus showed a strong negative association with subjective sleepiness, and conversely, the number of negative functional connectivity showed a positive association with subjective sleepiness. Arterial spin labeling analysis indicated that the blood flow in both the left and right thalami was significantly negatively associated with subjective sleepiness. Functional connectivity between the anterior cingulate cortex and salience network areas of the left insular cortex, and that between the anterior and posterior cingulate cortices showed a strong positive and negative association with subjective sleepiness, respectively. CONCLUSION: Subjective sleepiness and the thalamic-cortical network dynamics are strongly related, indicating the application of graph theory to study sleepiness and consciousness. These results also demonstrate that resting functional connectivity largely reflects the "state" of the subject, suggesting that the control of sleep and conscious states is essential when using functional magnetic resonance imaging indices as biomarkers.