Is the use of high correlated color temperature light at night related to delay of sleep timing in university students? A cross-country study in Japan and China.

BACKGROUND: Blue-enriched white light at night has the potential to delay the circadian rhythm in daily life. This study was conducted to determine whether the use of high correlated color temperature (CCT) light at home at night is associated with delay of sleep timing in university students. METHODS: The survey was conducted in 2014-2015 in 447 university students in Japan and 327 students in China. Habitual sleep timing and type of CCT light at home were investigated by using a self-administered questionnaire. The Japanese students were significantly later than the Chinese students in bedtime, wake time, and midpoint of sleep. They were asked whether the lighting in the room where they spend most of their time at night was closer to warm color (low CCT) or daylight color (high CCT). The amount of light exposure level during daily life was measured for at least 1 week by the use of a light sensor in 60 students in each country. RESULTS: The percentages of participants who used high CCT lighting at night were 61.6% for Japanese students and 80.8% for Chinese students. Bedtime and sleep onset time on school days and free days were significantly later in the high CCT group than in the low CCT group in Japan. The midpoint of sleep in the high CCT group was significantly later than that in the low CCT group on free days but not on school days. On the other hand, none of the sleep measurements on school days and free days were significantly different between the high CCT and low CCT groups in China. Illuminance level of light exposure during the night was significantly higher in Japanese than in Chinese, but that in the morning was significantly higher in China than in Japan. CONCLUSIONS: The use of high CCT light at night is associated with delay of sleep timing in Japanese university students but not in Chinese university students. The effects of light at night on sleep timing and circadian rhythm may be complicated by other lifestyle factors depending on the country.

Non-visual effects of diurnal exposure to an artificial skylight, including nocturnal melatonin suppression.

BACKGROUND: Recently, more consideration is being given to the beneficial effects of lighting on the maintenance and promotion of the health and well-being of office occupants in built environments. A new lighting technology using Rayleigh scattering has made it possible to simulate a blue sky. However, to date, no studies have examined the possible beneficial effects of such artificial skylights. The aims of this study were to examine the non-visual effects of artificial skylights and conventional fluorescent lights in a simulated office environment and to clarify the feature effects of the artificial skylights. METHODS: Participants were 10 healthy male adults. Non-visual effects were evaluated based on brain arousal levels (α-wave ratio and contingent negative variation [CNV]), autonomic nervous activity (heart rate variability [HRV]), work performance, and subjective responses during daytime exposure to either an artificial skylight or fluorescent lights, as well as nocturnal melatonin secretion. RESULTS: Subjective evaluations of both room lighting-related "natural" and "attractive" items and the "connected to nature" item were significantly higher with the skylight than with the fluorescent lights. Cortical arousal levels obtained from the early component of the CNV amplitude were significantly lower with the skylight than with the fluorescent lights, whereas α-wave ratio and work performance were similar between the two light sources. The HRV evaluation showed that sympathetic nerve tone was lower and parasympathetic nerve tone was higher, both significantly, for the skylight than for the fluorescent lights during daytime. Nocturnal melatonin secretion was significantly greater before and during light exposure at night under the daytime skylight than under the fluorescent lights. CONCLUSIONS: Our results suggest that artificial skylights have some advantages over conventional fluorescent lights in maintaining ordinary work performance during daytime with less psychological and physiological stress. The findings also suggest that the artificial skylights would enable built environments to maintain long-term comfort and productivity.

An ancestral haplotype of the human PERIOD2 gene associates with reduced sensitivity to light-induced melatonin suppression.

Humans show various responses to the environmental stimulus in individual levels as "physiological variations." However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, PER2 and PER3, exhibiting geographical differentiation of allele frequencies. Among the haplotypes of PER3, no significant difference in light sensitivity was found. However, three common haplotypes of PER2 accounted for more than 96% of the chromosomes in subjects, and 1 of those 3 had a significantly low-sensitive response to light-stimulus (P < 0.05). The homozygote of the low-sensitive PER2 haplotype showed significantly lower percentages of melatonin suppression (P < 0.05), and the heterozygotes of the haplotypes varied their ratios, indicating that the physiological variation for light-sensitivity is evidently related to the PER2 polymorphism. Compared with global haplotype frequencies, the haplotype with a low-sensitive response was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree, suggesting that the low light-sensitive haplotype is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types. Hence, we speculate that the high light-sensitive haplotypes have spread throughout the world after the Out-of-Africa migration of modern humans.

Human genetic research, race, ethnicity and the labeling of populations: recommendations based on an interdisciplinary workshop in Japan.

BACKGROUND: A challenge in human genome research is how to describe the populations being studied. The use of improper and/or imprecise terms has the potential to both generate and reinforce prejudices and to diminish the clinical value of the research. The issue of population descriptors has not attracted enough academic attention outside North America and Europe. In January 2012, we held a two-day workshop, the first of its kind in Japan, to engage in interdisciplinary dialogue between scholars in the humanities, social sciences, medical sciences, and genetics to begin an ongoing discussion of the social and ethical issues associated with population descriptors. DISCUSSION: Through the interdisciplinary dialogue, we confirmed that the issue of race, ethnicity and genetic research has not been extensively discussed in certain Asian communities and other regions. We have found, for example, the continued use of the problematic term, "Mongoloid" or continental terms such as "European," "African," and "Asian," as population descriptors in genetic studies. We, therefore, introduce guidelines for reporting human genetic studies aimed at scientists and researchers in these regions. CONCLUSION: We need to anticipate the various potential social and ethical problems entailed in population descriptors. Scientists have a social responsibility to convey their research findings outside of their communities as accurately as possible, and to consider how the public may perceive and respond to the descriptors that appear in research papers and media articles.

Melanopsin gene polymorphism I394T is associated with pupillary light responses in a dose-dependent manner.

BACKGROUND: Melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) play an important role in non-image forming responses to light, such as circadian photoentrainment, light-induced melatonin suppression, and pupillary light response. Although it is known that there are some single nucleotide polymorphisms (SNPs) in the melanopsin (OPN4) gene in humans, the associations of the SNPs with non-image forming responses to light remains unclear. In the present study, we examined the associations of melanopsin gene polymorphisms with pupillary light response. METHODS: Japanese university students (mean age: 21.0 ± 1.7 years) with the genotypes of TT (n = 38), TC (n = 28) and CC (n = 7) at rs1079610 (I394T) located in the coding region participated in the present study. They were matched by age and sex ratio. Dark-adapted pupil size (<1 lx) was first measured. Then steady-state pupil size was measured during exposure to five lighting conditions (10 lx, 100 lx, 1000 lx, 3000 lx, 6000 lx in the vertical direction at eye level). RESULTS: Significant interaction between the genotype of I394T (TT versus TC+CC) and luminance levels was found in pupil size. Under high illuminance levels (1000 lx, 3000 lx and 6000 lx), pupil sizes in subjects with the C allele were significantly smaller than those in subjects with the TT genotype. On the other hand, pupil size in subjects with the C allele under low illuminance (<1 lx) was significantly larger than that in subjects with the TT genotype. Percentages of pupil constriction under high illuminance levels were significantly greater in subjects with the C allele than in subjects with the TT genotype. CONCLUSIONS: Human melanopsin gene polymorphism I394T interacted with irradiance in association with pupil size. This is the first evidence suggesting a functional connection between melanopsin gene polymorphism and pupillary light response as an index of non-image forming response to light.

Comparison of cardiovascular response to sinusoidal and constant lower body negative pressure with reference to very mild whole-body heating.

BACKGROUND: The purpose of the present study was to compare sinusoidal versus constant lower body negative pressure (LBNP) with reference to very mild whole-body heating. Sinusoidal LBNP has a periodic load component (PLC) and a constant load component (CLC) of orthostatic stress, whereas constant LBNP has only a CLC. We tested two sinusoidal patterns (30-s and 180-s periods with 25 mmHg amplitude) of LBNP and a constant LBNP with -25 mmHg in 12 adult male subjects. RESULTS: Although the CLC of all three LBNP conditions were configured with -25 mmHg, the mean arterial pressure (MAP) results showed a significantly large decrease from baseline in the 30-s period condition (P <0.01). In contrast, the other cardiovascular indices (heart rate (HR), stroke volume (SV), cardiac output (CO), basal thoracic impedance (Z(0)), total peripheral resistance (TPR), the natural logarithmic of the HF component (lnHF), and LF/HF (ln(LF/HF))) of heart rate variability (HRV) showed relatively small variations from baseline in the 30-s period condition (P <0.01). The result of the gain and phase of transfer function at the sinusoidal period of LBNP showed that the very mild whole-body heating augmented the orthostatic responses. CONCLUSION: These results revealed that the effect of the CLC of LBNP on cardiovascular adjustability was attenuated by the addition of the PLC to LBNP. Based on the results of suppressed HRV response from baseline in the 30-s period condition, we suggest that the attenuation may be caused by the suppression of the vagal responsiveness to LBNP.

Cognitive characteristics of older Japanese drivers.

BACKGROUND: Some causes of accidents among older drivers are: not paying attention to traffic signals; missing stop lines; and having to deal with and misjudging emergency situations. These causes of accidents reveal problems with attention and cognition. Such incidents are also related to driver perception and stress-coping mechanisms. It is important to examine the relation of stress reactions to attention and cognition as a factor influencing the causes of accidents commonly involving older drivers. FINDING: Subjects were 10 young drivers (23.3 ± 3.33 years) and 25 older drivers divided into two groups (older1 [60 to 65 years] and older2 [> 65 years]). This study revealed the correlation within driver stress inventory and driver coping questionnaires parameters was observed only in older drivers. They also needed a longer response time for Trail Making Test A and B. The factors affected the attention and cognition of older drivers by age but not driving experience itself, and coping parameters such as emotion focus, reappraisal, and avoidance were not included as stress inventory parameters. Being prone to fatigue was less for younger drivers than older drivers. Because they have shorter distances, shorter drive times, and no need for expressways, older drivers also had a significantly lower risk of thrill-seeking behaviour and more patience. CONCLUSION: The intervention addressing their attention skills, aggressive feelings, and emotion focus should be considered. The technological improvements in cars will make older drivers feel safer and make driving easier which might lower the attention paid to the road, and regular driving training might be needed to assess and enhance their safety.

Distinct responses of cones and melanopsin-expressing retinal ganglion cells in the human electroretinogram.

BACKGROUND: The discovery of the novel photoreceptor, melanopsin-expressing retinal ganglion cells (mRGCs), has raised researchers' interest in photoreceptive tasks performed by the mRGC, especially in non-image-forming visual functions. In a prior study, we investigated the mRGC response to light stimuli independent of rods and cones with the four-primary illumination system, which modulates stimulus levels to the mRGC and cones independently, and mRGC baseline responses were recorded in the electroretinogram (ERG). METHODS: In the present study, we used the same illumination system to compare independent responses of the mRGC and cones in five subjects (mean ± SD age, 23.0 ± 1.7 years). The ERG waveforms were examined as direct measurements of responses of the mRGCs and cones to stimulation (250 msec). Implicit times (the time taken to peaks) and peak values from 30 stimuli given to each subject were analyzed. RESULTS: Two distinct positive peaks appeared in the mRGC response, approximately 80 msec after the onset of the stimuli and 30 msec after their offset, while no such peaks appeared in the cone response. The response to the mRGC stimulus was significantly higher than that to the cone stimulus at approximately 80 msec (P < 0.05) and tended to be higher than the cone stimulus at approximately 280 msec (P = 0.08). CONCLUSIONS: Implicit time of the first peak was much longer than that to the b-wave and this delay might reflect mRGC's sluggish responses. This is the first report of amplitudes and implicit time in the ERG from the response of the mRGC that is independent of rods and cones, and obtained using the four-primary illumination system.

Effect of reduced illumination on insomnia in office workers.

OBJECTIVE: We evaluated the possible effects of reduced illumination in the workplace on insomnia among office workers. METHODS: Seventy-two office workers answered the Athens Insomnia Scale (AIS) in July 2009 (under ordinary illumination, 01 conditions) and July 2010 (under reduced illumination, Rl conditions). The workers were divided into three groups, indoor workers (IWs), semi-outdoor workers (SWs) and outdoor workers (OWs), according to the frequency of working outside of the office because a worker with a high frequency of working outside of the office might rarely be exposed to the lighting condition within an office. The first five items of the AIS (AIS-5) were used to assess sleep difficulties, and the last three items (AIS-3) assessed next-day consequences of sleep or daytime symptoms, which often result from insomnia and/or sleep disorders. RESULTS: Illuminance levels at a height of 1,100 mm from the floor under the Rl conditions (550-490 lux) were significantly lower than under the Ol conditions (750-700 lux). The AIS-5 score of the IWs was significantly increased under the Rl conditions compared with the Ol conditions. There was no difference in AIS-3 scores between conditions for any group. CONCLUSION: Indoor workers hardly went outside of the office and were exposed only to office light during the daytime. Thus, the underexposure to light could have had an impact on insomnia in those individuals. A novel lighting environment is required to optimize work-related levels of light exposure.

Effects of load and gradient on energy cost of running.

This study quantified the interaction of electromyography (EMG) obtained from the vastus lateralis and metabolic energy cost of running (C(r); mL·[mass+load](-1)·meter(-1)), an index of running economy, during submaximal treadmill running. Experiments were conducted with and without load on the back on a motor-driven treadmill on the downhill, level and uphill slopes. The obtained EMG was full-wave rectified and integrated (iEMG). The iEMG was divided into eccentric (ECC) and concentric (CON) phases with a foot sensor and a knee-joint goniometer. The ratio of ECC to CON (ECC/CON ratio) was regarded as the muscle elastic capacity during running on each slope. The C(r) was determined as the ratio of the 2-min steady-state VO(2) to the running speed. We found a significant decrease in the C(r) when carrying the load at all slopes. The ECC/CON ratio was significantly higher in the load condition at the downhill and level slopes, but not at the uphill slope. A significant gradient difference was observed in the C(r) (downuphill). Thus, an alteration of Cr by the gradient and load was almost consistent with that of the ECC/CON ratio. The ECC/CON ratio, but not the rotative torque (T) functioning around the center of body mass, significantly correlated with C(r) (r=-0.41, p<0.05). These results indicated that the ECC/CON ratio, rather than T, contributed to one of the energy-saving mechanisms during running with load.

Effects of different light intensities in the morning on dim light melatonin onset.

The present study evaluated the effects of exposure to light intensity in the morning on dim light melatonin onset (DLMO). The tested light intensities were 750 lux, 150 lux, 3000 lux, 6000 lux and 12,000 lux (horizontal illuminance at cornea), using commercial 5000 K fluorescent lamps. Eleven healthy males aged 21-31 participated in 2-day experiments for each light condition. On the first experimental day (day 1), subjects were exposed to dim light (<30 lux) for 3 h in the morning (09:00-12:00). On the same day, saliva samples were taken in dim light (<30 lux) every 30 min from 21:00 to 01:00 to determine the DLMO phase. The subjects were allowed to sleep from 01:00 to 08:00. On the second experimental day (day 2), the subjects were exposed to experimental light conditions for 3 h in the morning. The experimental schedule after light exposure was the same as on day 1. On comparing day 2 with day 1, significant phase advances of DLMO were obtained at 3000 lux, 6000 lux and 12,000 lux. These findings indicate that exposure to a necessary intensity from an ordinary light source, such as a fluorescent lamp, in the morning within one day affects melatonin secretion.

Effects of saliva collection using cotton swabs on melatonin enzyme immunoassay.

BACKGROUND: Although various acceptable and easy-to-use devices have been used for saliva collection, cotton swabs are among the most common ones. Previous studies reported that cotton swabs yield a lower level of melatonin detection. However, this statistical method is not adequate for detecting an agreement between cotton saliva collection and passive saliva collection, and a test for bias is needed. Furthermore, the effects of cotton swabs have not been examined at lower melatonin level, a level at which melatonin is used for assessment of circadian rhythms, namely dim light melatonin onset (DLMO). In the present study, we estimated the effect of cotton swabs on the results of salivary melatonin assay using the Bland-Altman plot at lower level. METHODS: Nine healthy males were recruited and each provided four saliva samples on a single day to yield a total of 36 samples. Saliva samples were directly collected in plastic tubes using plastic straws, and subsequently pipetted onto cotton swabs (cotton saliva collection) and into clear sterile tubes (passive saliva collection). The melatonin levels were analyzed in duplicate using commercially available ELISA kits. RESULTS: The mean melatonin concentration in cotton saliva collection samples was significantly lower than that in passive saliva collection samples at higher melatonin level (>6 pg/mL). The Bland-Altman plot indicated that cotton swabs causes relative and proportional biases in the assay results. For lower melatonin level (<6 pg/mL), although the BA plots didn't show proportional and relative biases, there was no significant correlation between passive and cotton saliva collection samples. CONCLUSION: Our findings indicate an interference effect of cotton swabs on the assay result of salivary melatonin at lower melatonin level. Cotton-based collection devices might, thus, not be suitable for assessment of DLMO.

The ERG responses to light stimuli of melanopsin-expressing retinal ganglion cells that are independent of rods and cones.

The mechanisms by which melanopsin-expressing retinal ganglion cells (mRGCs) regulate circadian rhythms in humans have not been established. To understand mRGC characteristics and their role independent of effects due to the rods and cones, mRGC responses should be induced or measured independent of cone and rod responses. In the present study, we obtained results from light stimuli which differentially induce only the mRGC response by using a receptor-silent substitution technique. The mRGCs responded linearly to contrast changes of light stimuli, whereas they showed complicated responses to frequency changes with regard to the latency of response time. These results suggest that mRGC behavior is not a simple response to the various frequencies found in solar light but may be related to intrinsic neural circuits with feedback connections in the mRGC pathway. The results in this study also demonstrated that the test stimuli affected only the mRGC response and that this could be successfully detected by using the electroretinogram (ERG).

Thermoregulatory effect in humans of suppressed endogenous melatonin by pre-sleep bright-light exposure in a cold environment.

This study investigated the physiological function of suppressed melatonin through thermoregulation in a cold environment. Interactions between thermoregulation directly affected by exposure to a cold environment and indirectly affected by endogenous melatonin suppression by bright-light exposure were examined. Ten male subjects were exposed to two different illumination intensities (30 and 5000 lux) for 4.5 h, and two different ambient temperatures (15 and 27 degrees C) for 2 h before sleep under dark and thermoneutral conditions. Salivary melatonin level was suppressed by bright light (p < 0.001), although the ambient temperature condition had no significant effect on melatonin. During sleep, significant effects of pre-sleep exposure to a cold ambient temperature (p < 0.001) and bright light (p < 0.01) on rectal temperature (T(re)) were observed. Pre-sleep, bright-light exposure led to an attenuated fall in T(re) during sleep. Moreover, T(re) dropped more precipitously after cold exposure than thermoneutral conditions (cold: -0.54 +/- 0.07 degrees C/h; thermoneutral: -0.16 +/- 0.03 degrees C/h; p < 0.001). Pre-sleep, bright-light exposure delayed the nadir time of T(re) under thermoneutral conditions (p < 0.05), while cold exposure masked the circadian rhythm with a precipitous decrease in T(re). A significant correlation between the T(re) nadir and melatonin level (r = -0.774, p < 0.05) indicated that inter-individual differences with higher melatonin levels lead to a reduction in T(re) after cold exposure. These results suggest that suppressed endogenous melatonin inhibits the downregulation of the body temperature set-point during sleep.

Effects of saliva collection using cotton swab on cortisol enzyme immunoassay.

Cotton swabs are among the most commonly used devices for collecting saliva, but various studies have reported that their use impacts the results of salivary cortisol assays. These studies, however, estimated this impact by comparing the average of the concentration and/or scatter plots. In the present study, we estimated the impact of cotton swabs on the results of salivary cortisol enzyme immunoassay (EIA) by Bland-Altman plot. Eight healthy males (aged 20-23 years) provided four saliva samples on different days to yield a total of 32 samples. Saliva samples were collected directly in plastic tubes using plastic straws and then pipetted onto cotton swabs (cotton saliva collection) and into clear sterile tubes (passive saliva collection). There was a lower correlation between cotton and passive saliva collection. Individually, four subjects showed a negative correlation between passive and cotton saliva collection. A Bland-Altman plot indicated that cotton swabs causes a proportional bias on the EIA assay result. Our findings indicate a considerable effect of using cotton swabs for saliva collection, and subject-specific variability in the impact. A Bland-Altman plot further suggests possible reasons for this effect.

Sex differences on components of mental rotation at different menstrual phases.

Male (n=18) and female (n=16) subjects completed a three-dimensional mental rotation task (MRT). The hormonal and MRT data were collected from female subjects at low (menstruation) and high (ovulation) estrogen phases. Each subject's reaction time (RT) and error rate (ER) were plotted to give the slope and intercept of the functions, relating performance to angular disparity. Males showed faster RT and lower ER compared to females at each menstrual phase; the difference arises from the slope. These findings suggest that there is a sex difference in mental rotation at each menstrual phase.

Effects of short wavelength control in polychromatic light sources on nocturnal melatonin secretion.

In this study, 12 healthy males were exposed to various light conditions (2300K, 3000K, 5000K and dim) for 1.5h at midnight. The conditions of 3000K and 5000K were created by commercial fluorescent lamps. The light at 2300K was achieved by fitting a 3000K fluorescent lamp with a special filter that absorbed short-wavelength light. The vertical illuminance level was kept at 200lx. Saliva samples were taken before and after the light exposure. The light at 5000K suppressed melatonin secretion acutely. The 2300K lamp condition appeared to have no effect on melatonin secretion as well as the dim condition, while melatonin secretion was measurably suppressed by the light at 3000K.