Effects of long-term individual housing of middle-aged female Octodon degus on spatial learning and memory in the Barnes maze task.

Introduction: Prolonged social isolation is a form of passive chronic stress that has consequences on human and animal behavior. The present study was undertaken to elucidate whether the long-term isolation would precipitate age-related changes in anxiety and spatial learning and memory in degus. Methods: We investigated the effects of long-term social isolation on anxiety levels in the light-dark test, and spatial orientation abilities in the Barnes maze. Middle-aged female Octodon degus were allocated to either group-housed (3 animals per cage) or individually-housed for 5 months. Results: Under this experimental condition, there were no significant group differences in the anxiety level tested in the light-dark test and in the motivation to escape from the Barnes maze. There were no significant differences in cortisol levels between individually- and group-housed animals. On the last acquisition training day of spatial learning, individually- housed animals had a significantly higher number of correct responses and a smaller number of reference and working memory errors than the group-housed animals. In addition, isolated animals showed a tendency for reference and working memory impairment on the retention trial, while group-housed degus showed improvement in these parameters. Discussion and conclusion: The present study indicates that prolonged social isolation during adulthood in female degus has a dual effect on spatial orientation. Specifically, it results in a significant improvement in acquisition skills but a slight impairment in memory retention. The obtained cognitive changes were not accompanied by modification in anxiety and cortisol levels.

Melatonin as a Mediator of the Gut Microbiota-Host Interaction: Implications for Health and Disease.

In recent years, the role played by melatonin on the gut microbiota has gained increasingly greater attention. Additionally, the gut microbiota has been proposed as an alternative source of melatonin, suggesting that this antioxidant indoleamine could act as a sort of messenger between the gut microbiota and the host. This review analyses the available scientific literature about possible mechanisms involved in this mediating role, highlighting its antioxidant effects and influence on this interaction. In addition, we also review the available knowledge on the effects of melatonin on gut microbiota composition, as well as its ability to alleviate dysbiosis related to sleep deprivation or chronodisruptive conditions. The melatonin-gut microbiota relationship has also been discussed in terms of its role in the development of different disorders, from inflammatory or metabolic disorders to psychiatric and neurological conditions, also considering oxidative stress and the reactive oxygen species-scavenging properties of melatonin as the main factors mediating this relationship.

Phase Response Curve to Light under Ambulatory Conditions: A Pilot Study for Potential Application to Daylight Saving Time Transitions.

Several studies have investigated the relationship between daylight saving time (DST) and sleep alterations, psychiatric disorders, cardiovascular events and traffic accidents. However, very few have monitored participants while maintaining their usual lifestyle before and after DST. Considering that DST transitions modify human behavior and, therefore, people's light exposure patterns, the aim of this study was to investigate the potential effects of DST on circadian variables, considering sleep and, for the first time, the human phase response curve to light. To accomplish this, eight healthy adults (33 ± 11 years old, mean ± SD) were recruited to monitor multivariable circadian markers and light exposure by means of a wearable ambulatory monitoring device: Kronowise®. The following night phase markers were calculated: midpoints of the five consecutive hours of maximum wrist temperature (TM5) and the five consecutive hours of minimum time in movement (TL5), sleep onset and offset, as well as sleep duration and light intensity. TM5 for wrist temperature was set as circadian time 0 h, and the balance between advances and delays considering the phase response curve to light was calculated individually before and after both DST transitions. To assess internal desynchronization, the possible shift in TM5 for wrist temperature and TL5 for time in movement were compared. Our results indicate that the transition to DST seems to force the circadian system to produce a phase advance to adapt to the new time. However, the synchronizing signals provided by natural and personal light exposure are not in line with such an advance, which results in internal desynchronization and the need for longer synchronization times. On the contrary, the transition back to ST, which implies a phase delay, is characterized by a faster adaptation and maintenance of internal synchronization, despite the fact that exposure to natural light would favor a phase advance. Considering the pilot nature of this study, further research is needed with higher sample sizes.

Living at the Wrong Time: Effects of Unmatching Official Time in Portugal and Western Spain.

Human circadian rhythmicity is subjected to the internal circadian clock, the sun and social clocks (official time, social/work schedules). The discrepancy among these clocks, as occurs when official time does not match its geographical time zone, may produce circadian disruption. Western Spain (GMT+1/+2) and Portugal (GMT0/+1) share similar longitudes (sun time) but have different official times. This provides a unique opportunity to evaluate the effects of official time on circadian rhythmicity and sleep in elderly and retired populations (with no remunerated duties presumed, although other social commitments may be present) at both locations. Although both populations slept enough for their age (7-8 h), circadian robustness (e.g., interdaily stability, relative amplitude) was greater in Portugal, especially during weekdays, while greater desynchronization (both body temperature vs. motor activity and body temperature vs. light exposure) tended to occur in the Spaniards. Once corrected by GMT0, meals took place later in Spain than in Portugal, especially as the day progresses, and a possible interplay between bed/meal timings and internal desynchronization was found. Our results point to the possible deleterious effect on circadian system robustness when official time is misaligned with its geographical time zone.

Chronodisruption and Ambulatory Circadian Monitoring in Cancer Patients: Beyond the Body Clock.

PURPOSE OF REVIEW: Circadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms' disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease. RECENT FINDINGS: In recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications. This review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the state-of-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer research.

Correlated color temperature and light intensity: Complementary features in non-visual light field.

An appropriate exposure to the light-dark cycle, with high irradiances during the day and darkness during the night is essential to keep our physiology on time. However, considering the increasing exposure to artificial light at night and its potential harmful effects on health (i.e. chronodisruption and associated health conditions), it is essential to understand the non-visual effects of light in humans. Melatonin suppression is considered the gold standard for nocturnal light effects, and the activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) through the assessment of pupillary light reflex (PLR) has been recently gaining attention. Also, some theoretical models for melatonin suppression and retinal photoreceptors activation have been proposed. Our aim in this study was to determine the influence of correlated color temperature (CCT) on melatonin suppression and PLR, considering two commercial light sources, as well as to explore the possible correlation between both processes. Also, the contribution of irradiance (associated to CCT) was explored through mathematical modelling on a wider range of light sources. For that, melatonin suppression and PLR were experimentally assessed on 16 healthy and young volunteers under two light conditions (warmer, CCT 3000 K; and cooler, CCT 5700 K, at ~5·1018 photons/cm2/sec). Our experimental results yielded greater post-stimulus constriction under the cooler (5700 K, 13.3 ± 1.9%) than under the warmer light (3000 K, 8.7 ± 1.2%) (p < 0.01), although no significant differences were found between both conditions in terms of melatonin suppression. Interestingly, we failed to demonstrate correlation between PLR and melatonin suppression. Although methodological limitations cannot be discarded, this could be due to the existence of different subpopulations of Type 1 ipRGCs differentially contributing to PLR and melatonin suppression, which opens the way for further research on ipRGCs projection in humans. The application of theoretical modelling suggested that CCT should not be considered separately from irradiance when designing nocturnal/diurnal illumination systems. Further experimental studies on wider ranges of CCTs and light intensities are needed to confirm these conclusions.

Behavioral and Thermoregulatory Responses to Changes in Ambient Temperature and Wheel Running Availability in Octodon degus.

Octodon degus is primarily a diurnal species, however, in laboratory conditions, it can switch from diurnal to nocturnal in response to wheel running availability. It has been proposed that this activity inversion obeys thermoregulatory constraints induced by vigorous physical exercise. Thus, its activity shifts to the night as the ambient temperature is lower.Here, we investigate the relationship between thermoregulation and the activity phase-inversion in response to wheel-running in this species. We measured behavioral activity and body temperature rhythms in diurnal naïve animals under 12 h light: 12 h dark cycles at four different ambient temperatures (spanning from ~26°C to 32°C), and following access to running wheels while maintained under high ambient temperature.Our results show that naïve degus do not shift their diurnal activity and body temperature rhythms to a nocturnal phase when subjected to sequential increases in ambient temperature. However, when they were provided with wheels under constant high-temperature conditions, all animals inverted their diurnal phase preference becoming nocturnal. Both, negative masking by light and entrainment to the dark phase appeared involved in the nocturnalism of these animals. Analysis of the thermoregulatory response to wheel running revealed some differences between masked and entrained nocturnal chronotypes.These data highlight the importance of the coupling between wheel running availability and ambient temperature in the nocturnalism of the degus. The results support the view that an innate "protective" pre-program mechanism (associating darkness and lower ambient temperature) may change the timing of behavioral activity in this species to reduce the potential risk of hyperthermia.

Ambulatory circadian monitoring in sleep disordered breathing patients and CPAP treatment.

Our aim was to evaluate the circadian rhythm of motor activity, body position and integrated variable TAP (composed by wrist Temperature, motor Activity and body Position) in Sleep Disordered Breathing (SDB), its relation to SDB severity and the effect of continuous positive airway pressure (CPAP) on these circadian rhythms. To do this, we monitored motor activity and body position rhythms of 78 SDB patients (53.3 ± 1.2 years old, 26.9% women) and 32 healthy subjects (51.4 ± 3.2 years old, 43.8% women) for 1 week. On the last day of that week, SDB patients underwent a polysomnography followed by a Maintenance of Wakefulness Test, Multiple Sleep Latency Test and Sustained Attention to Response Task protocol. A subgroup of 18 moderate to severe SDB patients was treated with CPAP and monitored again after 3 months under treatment. A non-parametrical analysis was performed to characterize the circadian patterns to assess differences between groups and associations between sleep and circadian parameters. Circadian variables were altered in SDB, exhibiting a direct relationship to SDB severity. The motor activity pattern showed a clear improvement with CPAP treatment. Thus, circadian ambulatory monitoring, including the integrated variable TAP, could be used to evaluate the circadian alterations caused by SDB and activity pattern to monitor the effect of CPAP treatment.

Widespread Doublecortin Expression in the Cerebral Cortex of the Octodon degus.

It has been demonstrated that in adulthood rodents show newly born neurons in the subgranular layer (SGL) of the dentate gyrus (DG), and in the subventricular zone (SVZ). The neurons generated in the SVZ migrate through the rostral migratory stream (RMS) to the olfactory bulb. One of the markers of newly generated neurons is doublecortin (DCX). The degu similarly shows significant numbers of DCX-labeled neurons in the SGL, SVZ, and RMS. Further, most of the nuclei of these DCX-expressing neurons are also labeled by proliferating nuclear antigen (PCNA) and Ki67. Finally, whereas in rats and mice DCX-labeled neurons are predominantly present in the SGL and SVZ, with only a few DCX neurons present in piriform cortex, the degu also shows significant numbers of DCX expressing neurons in areas outside of SVZ, DG, and PC. Many areas of neocortex in degu demonstrate DCX-labeled neurons in layer II, and most of these neurons are found in the limbic cortices. The DCX-labeled cells do not stain with NeuN, indicating they are immature neurons.

Activity-rest circadian pattern and academic achievement, executive function, and intelligence in children with obesity.

This study aimed to analyze the associations of activity-rest pattern indicators with academic achievement, executive function, and intelligence and to explore whether these associations are mediated by the total gray matter volume among children with overweight/obesity. Ninety-five children (10 ± 1 year, 37 girls) with overweight/obesity (based on the World Obesity Federation body mass index cutoff points) were included in this cross-sectional study. Hip- and wrist-worn ActiGraph GT3X + accelerometers were used to assess the activity-rest pattern. Interdaily stability (IS), intradaily variability (IV), the mean value of the lowest 5 hours (L5), and the mean value of the maximum 10 hours (M10) of activity and their respective timing (TL5, TM10) were used as indicators of the activity-rest pattern throughout the day. Chronotype and social jetlag were used as indicators of circadian preference. Academic achievement, executive function, and intelligence were assessed with standardized tests. Gray matter volume was acquired by magnetic resonance imaging (MRI). IS was positively associated with executive function (ß = 0.244, P = .014). IV was negatively associated with mathematics and academic applications (ß: -0.211 to -0.238, P's ≤ .026). Later TM10 in the day was related to lower writing, academic skills, and intelligence (ß: -0.229 to -0.271, P's ≤ .025). None of the associations found were mediated by gray matter volume. A non-fragmented and stable activity-rest pattern and earlier physical activity in the day were associated with better academic achievement, executive function, and intelligence in children with overweight/obesity. Further studies are required to corroborate or contrast our findings.

Electrochromic selective filtering of chronodisruptive visible wavelengths.

We present evidence of pupil response modification, as well as differential theoretical melatonin suppression through selective and dynamic electrochromic filtering of visible light in the 400-500 nm range to minimize chronodisruptive nocturnal blue light exposure. A lower activation of intrinsically photosensitive retinal ganglion cells (ipRGCs), the first step for light to reach a human's internal clock, is related to melatonin secretion therefore avoiding detrimental effects of excessive blue light exposure. Pupillary Light Reflex and Color Naming were experimentally assessed under light filtered by two different coloration states (transmissive and absorptive) of these novel dynamic filters, plus an uncoated test device, in 16 volunteers. Also, different commercial light sources at illuminances ranging from 1 to 1000 lux were differentially filtered and compared in terms of theoretical melatonin suppression. Representative parameters of the pupil responses reflected lower pupil constriction when the electrochromic filters (ECFs) were switched on (absorptive state, blue light is absorbed by the filter) compared to uncoated filters (control sample), but failed to do so under transmissive state (blue light passes through the filter) indicating less activation of ipRGCs under absorptive state (although no significant differences between states was found). Out of eight colors tested, just one showed significant differences in naming between both filter states. Thus, the ECF would have some protecting effect on ipRGC activation with very limited changes in color perception. While there are some limitations of the theoretical model used, the absorptive state yielded significantly lower theoretical melatonin suppression in all those light sources containing blue wavelengths across the illuminance range tested. This would open the way for further research on biological applications of electrochromic devices.

Living Without Temporal Cues: A Case Study.

Isolation from external time cues allows endogenous circadian rhythmicity to be demonstrated. In this study, also filmed as a television documentary, we assessed rhythmic changes in a healthy man time isolated in a bunker for 9 days/nights. During this period the lighting conditions were varied between: (1) self-selected light/dark cycle, (2) constant dim light, and (3) light/dark cycle with early wake up. A range of variables was assessed and related to the sleep-wake cycle, psychomotor and physical performance and clock-time estimation. This case study using modern non-invasive monitoring techniques emphasizes how different physiological circadian rhythms persist in temporal isolation under constant dim light conditions with different waveforms, free-running with a period (τ) between 24 and 25 h. In addition, a significant correlation between time estimation and mid-sleep time, a proxy for circadian phase, was demonstrated.

Melatonin alleviates circadian system disruption induced by chronic shifts of the light-dark cycle in Octodon degus.

Modern 24-h society lifestyle is associated with experiencing frequent shifts in the lighting conditions which can negatively impact human health. Here, we use the degus, a species exhibiting diurnal and nocturnal chronotypes, to: (a) assess the impact of chronic shifts of the light:dark (LD) cycle in the animal's physiology and behaviour and (b) test the therapeutic potential of melatonin in enhancing rhythmicity under these conditions. Degus were subjected to a "5d + 2d" LD-shifting schedule for 19 weeks. This protocol aims to mimic lighting conditions experienced by humans during shift work: LD cycle was weekly delayed by 8h during 5 "working" days (Morning, Afternoon and Night schedule); during weekends (2 days), animals were kept under Morning schedule. After 9 weeks, melatonin was provided daily for 6h in the drinking water. The "5d + 2d" shifting LD schedule led to a disruption in wheel-running activity (WRA) and body temperature (Tb) rhythms which manifested up to three separate periods in the circadian range. This chronodisruption was more evident in nocturnal than in diurnal degus, particularly during the Afternoon schedule when a phase misalignment between WRA and Tb rhythms appeared. Melatonin treatment and, to a lesser extent, water restriction enhanced the 24-h component, suggesting a potential role in ameliorating the disruptive effects of shift work.

Assessing Chronotypes by Ambulatory Circadian Monitoring.

In order to develop objective indexes for chronotype identification by means of direct measurement of circadian rhythms, 159 undergraduate students were recruited as volunteers and instructed to wear ambulatory circadian monitoring (ACM) sensors that continuously gathered information on the individual's environmental light and temperature exposure, wrist temperature, body position, activity, and the integrated TAP (temperature, activity, and position) variable for 7 consecutive days under regular free-living conditions. Among all the proposed indexes, the night phase marker (NPM) of the TAP variable was the best suited to discriminate among chronotypes, due to its relationship with the Munich ChronoType Questionnaire (ß = 0.531; p < 0.001). The NPM of TAP allowed subjects to be classified as early- (E-type, 20%), neither- (N-type, 60%), and late-types (L-type, 20%), each of which had its own characteristics. In terms of light exposure, while all subjects had short exposure times to bright light (>100 lux), with a daily average of 93.84 ± 5.72 min, the earlier chronotypes were exposed to brighter days and darker nights compared to the later chronotypes. Furthermore, the earlier chronotypes were associated with higher stability and day-night contrast, along with an earlier phase, which could be the cause or consequence of the light exposure habits. Overall, these data support the use of ACM for chronotype identification and for evaluation under free living conditions, using objective markers.

Determining Light Intensity, Timing and Type of Visible and Circadian Light From an Ambulatory Circadian Monitoring Device.

During last decades, the way of life in modern societies has deeply modified the temporal adjustment of the circadian system, mainly due to the inappropriate use of artificial lighting and the high prevalence of social jet-lag. Therefore, it becomes necessary to design non-invasive and practical tools to monitor circadian marker rhythms but also its main synchronizer, the light-dark cycle under free-living conditions. The aim of this work was to improve the ambulatory circadian monitoring device (ACM, Kronowise®) capabilities by developing an algorithm that allows to determine light intensity, timing and circadian light stimulation by differentiating between full visible, infrared and circadian light, as well as to discriminate between different light sources (natural and artificial with low and high infrared composition) in subjects under free living conditions. The ACM device is provided with three light sensors: (i) a wide-spectrum sensor (380-1100 nm); (ii) an infrared sensor (700-1100 nm) and (iii) a sensor equipped with a blue filter that mimics the sensitivity curve of the melanopsin photopigment and the melatonin light suppression curve. To calibrate the ACM device, different commercial light sources and sunlight were measured at four different standardized distances with both a spectroradiometer (SPR) and the ACM device. CIE S 026/E:2018 (2018), toolbox software was used to calculate the melanopic stimulation from data recorded by SPR. Although correlation between raw data of luminance measured by ACM and SPR was strong for both full spectrum (r = 0.946, p < 0.0001) and circadian channel (r = 0.902, p < 0.0001), even stronger correlations were obtained when light sources were clustered in three groups: natural, infrared-rich artificial light and infrared-poor artificial light, and their corresponding linear correlations with SPR were considered (r = 0.997, p < 0.0001 and r = 0.998, p < 0.0001, respectively). Our results show that the ACM device provided with three light sensors and the algorithm developed here allow an accurate detection of light type, intensity and timing for full visible and circadian light, with simultaneous monitoring of several circadian marker rhythms that will open the possibility to explore light synchronization in population groups while they maintain their normal lifestyle.

Validation of a Device for the Ambulatory Monitoring of Sleep Patterns: A Pilot Study on Parkinson's Disease.

The development of wearable devices has increase interest in the use of ambulatory methods to detect sleep disorders more objectively than those permitted by subjective scales evaluating sleep quality, while subjects maintain their usual lifestyle. This study aims to validate an ambulatory circadian monitoring (ACM) device for the detection of sleep and wake states and apply it to the evaluation of sleep quality in patients with Parkinson disease (PD). A polysomnographic validation study was conducted on a group of patients with different sleep disorders in a preliminary phase, followed by a pilot study to apply this methodology to PD patients. The ACM device makes it possible to estimate the main sleep parameters very accurately, as demonstrated by: (a) the lack of significant differences between the mean values detected by PSG and ACM in time in bed (TIB), total sleep time (TST), sleep efficiency (SE), and time awake after sleep onset (WASO); (b) the slope of the correlation lines between the parameters estimated by the two procedures, very close to 1, which demonstrates the linearity of the predictions; (c) the low bias value in the estimates obtained through ACM. Sleep in PD is associated with lower distal skin temperature, efficiency and overall sleep time; greater WASO, activity during sleep and duration of naps and a worse circadian function index. In summary, the ACM device has proven to be clinically useful to evaluate sleep in an objective manner, thanks to the integrated management of different complementary variables, having advantages over conventional actigraphy.

Targeting neurons in the gastrointestinal tract to treat Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is associated with α-synuclein (αS) aggregation within the enteric nervous system (ENS) and constipation. Squalamine displaces proteins that are electrostatically bound to intracellular membranes and through this mechanism suppresses aggregation of αS monomers into neurotoxic oligomers. OBJECTIVE: We sought to evaluate the safety of ENT-01 oral tablets (a synthetic squalamine salt), its pharmacokinetics, and its effect on bowel function in PD patients with constipation. METHODS: In Stage 1, 10 patients received escalating single doses from 25 to 200 mg/day or maximum tolerated dose (MTD). In Stage 2, 34 patients received daily doses escalating from 75 to a maximum of 250 mg/day, a dose that induced change in bowel function or MTD, followed by a fixed dose for 7 days, and a 2-week washout. Primary efficacy endpoint was defined as an increase of 1 complete spontaneous bowel movement (CSBM)/week, or 3 CSBM/week over the baseline period, as defined by FDA guidelines for prokinetic agents. Safety was also assessed. RESULTS: Over 80% of patients achieved the primary efficacy endpoint, with the mean number of CSBM/week increasing from 1.2 at baseline to 3.6 during fixed dosing (p = 1.2 × 10-7). Common adverse events included nausea in 21/44 (47%) and diarrhea in 18/44 (40%) patients. Systemic absorption was <0.3%. CONCLUSIONS: Orally administered ENT-01 was safe and significantly improved bowel function in PD, suggesting that the ENS is not irreversibly damaged in PD. Minimal systemic absorption suggests that improvements result from local stimulation of the ENS. A double-blind, placebo-controlled study is now ongoing.

Application of Machine Learning Methods to Ambulatory Circadian Monitoring (ACM) for Discriminating Sleep and Circadian Disorders.

The present study proposes a classification model for the differential diagnosis of primary insomnia (PI) and delayed sleep phase disorder (DSPD), applying machine learning methods to circadian parameters obtained from ambulatory circadian monitoring (ACM). Nineteen healthy controls and 242 patients (PI = 184; DSPD = 58) were selected for a retrospective and non-interventional study from an anonymized Circadian Health Database (https://kronowizard.um.es/). ACM records wrist temperature (T), motor activity (A), body position (P), and environmental light exposure (L) rhythms during a whole week. Sleep was inferred from the integrated variable TAP (from temperature, activity, and position). Non-parametric analyses of TAP and estimated sleep yielded indexes of interdaily stability (IS), intradaily variability (IV), relative amplitude (RA), and a global circadian function index (CFI). Mid-sleep and mid-wake times were estimated from the central time of TAP-L5 (five consecutive hours of lowest values) and TAP-M10 (10 consecutive hours of maximum values), respectively. The most discriminative parameters, determined by ANOVA, Chi-squared, and information gain criteria analysis, were employed to build a decision tree, using machine learning. This model differentiated between healthy controls, DSPD and three insomnia subgroups (compatible with onset, maintenance and mild insomnia), with accuracy, sensitivity, and AUC >85%. In conclusion, circadian parameters can be reliably and objectively used to discriminate and characterize different sleep and circadian disorders, such as DSPD and OI, which are commonly confounded, and between different subtypes of PI. Our findings highlight the importance of considering circadian rhythm assessment in sleep medicine.

Light color importance for circadian entrainment in a diurnal (Octodon degus) and a nocturnal (Rattus norvegicus) rodent.

The central circadian pacemaker (Suprachiasmatic Nuclei, SCN) maintains the phase relationship with the external world thanks to the light/dark cycle. Light intensity, spectra, and timing are important for SCN synchronisation. Exposure to blue-light at night leads to circadian misalignment that could be avoided by using less circadian-disruptive wavelengths. This study tests the capacity of a diurnal Octodon degus and nocturnal Rattus norvegicus to synchronise to different nocturnal lights. Animals were subjected to combined red-green-blue lights (RGB) during the day and to: darkness; red light (R); combined red-green LED (RG) lights; and combined red-green-violet LED (RGV) lights during the night. Activity rhythms free-ran in rats under a RGB:RG cycle and became arrhythmic under RGB:RGV. Degus remained synchronised, despite the fact that day and night-time lighting systems differed only in spectra, but not in intensity. For degus SCN c-Fos activation by light was stronger with RGB-light than with RGV. This could be relevant for developing lighting that reduces the disruptive effects of nocturnal light in humans, without compromising chromaticity.

Circadian Impairment of Distal Skin Temperature Rhythm in Patients With Sleep-Disordered Breathing: The Effect of CPAP.

Study objectives: Our aim was to evaluate the circadian rhythm of distal skin temperature (DST) in sleep-disordered breathing (SDB), its relation to excessive daytime sleepiness and the effect of continuous positive airway pressure (CPAP) on DST. Methods: Eighty SDB patients (53.1 ± 1.2 years old, 27.6% women) and 67 healthy participants (52.3 ± 1.6 years old, 26.9% women) wore a temperature data logger for 1 week. On the last day of that week, SDB patients underwent a polysomnography followed by a Maintenance of Wakefulness Test (MWT), Multiple Sleep Latency Test, and Sustained Attention to Response Task protocol to objectively quantify daytime sleepiness. A subset of 21 moderate to severe SDB patients were treated with CPAP during at least 3 months and revaluated with the same procedure. A nonparametric analysis was performed to characterize DST to assess differences between groups and associations among DST, polysomnography, and daytime sleepiness measures. Results: SDB patients showed an unstable, fragmented, flattened, phase-advanced, and less robust DST rhythm as compared to healthy participants. The more severe the SDB, the worse the DST pattern was, as indicated by the correlation coefficient. Sleepiness, according to MWT sleep latencies, was also associated with the higher fragmentation, lower amplitude, and less robustness of the DST rhythm. Treatment with CPAP improved DST pattern regularity and robustness. Conclusion: DST is altered in SDB, exhibiting a direct relationship to the severity of this condition, and improves with CPAP treatment. DST independently correlates with sleepiness, thus, its measurement may contribute to the understanding of the pathophysiology of sleepiness in these patients.