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Changes in circadian rhythms have been observed in patients with chronic kidney disease (CKD), and evidence suggests that these changes can have a negative impact on health. This study aimed to investigate the existence of hemodialysis-induced chronodisruption, the chronotype distribution, and their association with sleep quality and quality of life (QoL). This was a cross-sectional study that enrolled 165 patients (mean age: 51.1 ± 12.5 y, 60.6% male) undergoing hemodialysis from three local units. The following instruments were used: the Morning-Eveningness Questionnaire (MEQ); a modified version of the Munich Chronotype Questionnaire (MCQT) to estimate hemodialysis-induced chronodisruption (HIC); the Kidney Disease QoL Short Form (KDQOL-SF); the Epworth Sleepiness Scale (ESS); the Pittsburgh Sleep Quality Index (PSQI) and the 10-Cognitive Screener (10-CS). HIC was present in 40.6% of CKD patients. Morning chronotype was prevalent in CKD patients (69%) compared to evening-type (17.1%) and significantly different from a paired sample from the general population ( p  < 0.001). HIC and chronotype were associated with different domains of QoL but not with sleep quality. This study suggests that there is a HIC and that morning chronotype is associated with CKD patients undergoing hemodialysis, with implications for QoL.

The molecular circadian timing system involves genes known as "clock genes," such as the PER3 gene. Studies have demonstrated associations among a repeat polymorphism (VNTR) of the PER3 gene with chronotypes, with the occurrence of circadian rhythm disorders and with sleep homeostasis phenotypes. The aim of this study was to investigate, by actigraphy, sleep and circadian rhythm profiles of people with different genotypes for the VNTR polymorphism of the PER3 gene. We genotyped 467 individuals (46,39% male) for the PER3 VNTR polymorphism. The mean age of the participants was 21.84 ± 2.64, ranging from 18 to 30 y old. Actigraphy data were collected from a subsample of 81 subjects with PER3 4-repeats homozygous ( PER3 4/4 ) or 5-repeats homozygous ( PER3 5/5 ) genotypes from April to June of 2021. From this sample, 48 PER3 4/4 and 33 PER3 5/5 subjects wore a wrist actigraph between 12 and 19 d. The sleep onset (weekdays, p  = 0.015; weekend, p  = 0.022) and offset (weekdays, p  = 0.004; weekend, p  = 0.041) of the PER3 5/5 group occurred later than the PER3 4/4 group. Similar results were observed for the mid-sleep phase of weekdays (MSW) ( p  = 0.008) and free days (MSF) ( p  = 0.019), and for the mid-sleep phase corrected for sleep debt accumulated over the week (MSFsc) ( p  = 0.024). Despite the phase differences found between the PER3 4/4 and PER3 5/5 groups, no differences were found in sleep duration and social jet lag. However, the PER3 4/4 group presented, on average, a longer sleep rebound on the days off when compared to the PER3 5/5 ( p  = 0.002). The PER3 5/5 group showed lower interdaily stability (IS) ( p  = 0.032) and higher daily activity rhythm variability (IV) ( p  = 0.035). The findings of the present study revealed associations between the PER3 gene, sleep, and circadian rhythms. In general, we found that the gene is associated with the expression of sleep timing and duration and to the phase of the activity rhythm. The experiments carried out here occurred in the COVID-19 pandemic scenario, which should be considered as an environmental element with potential effects on the results obtained.

Aims: To investigate the influence of fasting during the night shift on eating behavior, hunger, glucose and insulin levels the following day., Methods: Study with 10 male police officers who have been working at night. Participants were tested under three different conditions separated by at least 6 days of washout in a randomized, crossover design: "Night Shift Fasting" (NSF)-two nights of fasting during the night shift; "Night Shift Eating" (NSE)-two nights with the consumption of a standardized meal during the night shift (678 ± 42 kcal consumed at ~ 0200 h); and "Nighttime Sleep" (NS)-two nights of sleep. The morning after, blood glucose and insulin and hunger ratings were assessed, and food intake was assessed with an ad libitum test meal. Food intake was also assessed throughout the remainder of the day using a food record. Generalized Estimating Equations were used to analyze the effect of experimental condition., Results: Food intake during the test meal, especially of proteins and fats, was higher after fasting during the night shift compared to the other conditions (p < 0.05), whereas desire to eat scores were lower after the NSF compared to NSE condition (p = 0.043). Hunger levels were lower after the NSF compared to the NS condition (p = 0.012). Insulin and HOMA-IR were also lower in the morning after NSF (p < 0.001)., Conclusion: Fasting during the night shift leads to not only a higher intake of energy and macronutrients both in the early morning after work and throughout the next day, but also lower insulin levels and HOMA-IR in the morning., Registration Number of Clinical Trial: NCT03800732. Initial release: 01/09/2019. Last release: 02/23/2022., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Stem cell engineering of striatal medium spiny neurons (MSNs) is a promising strategy to understand diseases affecting the striatum and for cell-replacement therapies in different neurological diseases. Protocols to generate cells from human pluripotent stem cells (PSCs) are scarce and how well they recapitulate the endogenous fetal cells remains poorly understood. We have developed a protocol that modulates cell seeding density and exposure to specific morphogens that generates authentic and functional D1- and D2-MSNs with a high degree of reproducibility in 25 days of differentiation. Single-cell RNA sequencing (scRNA-seq) shows that our cells can mimic the cell-fate acquisition steps observed in vivo in terms of cell type composition, gene expression, and signaling pathways. Finally, by modulating the midkine pathway we show that we can increase the yield of MSNs. We expect that this protocol will help decode pathogenesis factors in striatal diseases and eventually facilitate cell-replacement therapies for Huntington's disease (HD)., Competing Interests: All authors declare no competing interests., (© 2022 The Authors.)

Objective: We tested the effect of later school start time (LSST) by 1 hour during 1 week on sleep, sleepiness, and mood profile using within-subject design., Design: A within-subject 3-weeks-long interventional study. A baseline week with school starting at 7:30 AM (week A), followed by an intervention week with school starting at 8:30 AM (week B), and a recovery week with school start time back to 7:30 AM (week C). Mixed model for repeated measures analysis was applied to test for the LSST effect between weeks., Setting: A private high school with high level of socioeconomic status., Participants: Forty-eight adolescents from 3 different high school years., Measurements: Participants were invited to wear actigraphs continuously during the 3 experimental weeks. Somnolence was obtained every school day twice, at arrival and before departure of school. Sleep quality and mood profile were evaluated by standard measures by the end of each school week, resulting in 3 repeated measures for each variable., Results: Thirty-eight adolescents completed the study. Adolescents woke up later during week B (7:42 ± 00:30) in comparison to weeks A (6:54 ± 00:12) and C (6:46 ± 00:15) (p &lt; .001), with no significant change on sleep onset between weeks (p = .657), resulting in a longer sleep duration in week B (p &lt; .001). Significant improvements on sleepiness and mood profile were also reported during week B., Conclusions: Starting school later was effective in improving multiple aspects from sleep patterns, subjective sleepiness, and mood profile., (Copyright © 2022 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Chronotype or diurnal preference is a questionnaire-based measure influenced both by circadian period and by the sleep homeostat. In order to further characterize the biological determinants of these measures, we used a hypothesis-free approach to investigate the association between the score of the morningness-eveningness questionnaire (MEQ) and the Munich chronotype questionnaire (MCTQ), as continuous variables, and volumetric measures of brain regions acquired by magnetic resonance imaging (MRI). Data were collected from the Baependi Heart Study cohort, based in a rural town in South-Eastern Brazil. MEQ and anatomical 1.5-T MRI scan data were available from 410 individuals, and MCTQ scores were available from a subset of 198 of them. The average MEQ (62.2 ± 10.6) and MCTQ (average MSFsc 201 ± 85 min) scores were suggestive of a previously reported strong general tendency toward morningness in this community. Setting the significance threshold at P > .002 to account for multiple comparisons, we observed a significant association between lower MEQ score (eveningness) and greater volume of the left anterior occipital sulcus (β = -0.163, p = .001) of the occipital lobe. No significant associations were observed for MCTQ. This may reflect the smaller dataset for MCTQ, and/or the fact that MEQ, which asks questions about preferred timings, is more trait-like than the MCTQ, which asks questions about actual timings. The association between MEQ and a brain region dedicated to visual information processing is suggestive of the increasingly recognized fluidity in the interaction between visual and nonvisual photoreception and the circadian system, and the possibility that chronotype includes an element of masking.

The perirhinal cortex (PRC) is a polymodal associative region of the temporal lobe that works as a gateway between cortical areas and hippocampus. In recent years, an increasing interest arose in the role played by the PRC in learning and memory processes, such as object recognition memory, in contrast with certain forms of hippocampus-dependent spatial and episodic memory. The integrative properties of the PRC should provide all necessary resources to select and enhance the information to be propagated to and from the hippocampus. Among these properties, we explore in this paper the ability of the PRC neurons to amplify the output voltage to current input at selected frequencies, known as membrane resonance. Within cerebral circuits the resonance of a neuron operates as a filter toward inputs signals at certain frequencies to coordinate network activity in the brain by affecting the rate of neuronal firing and the precision of spike timing. Furthermore, the ability of the PRC neurons to resonate could have a fundamental role in generating subthreshold oscillations and in the selection of cortical inputs directed to the hippocampus. Here, performing whole-cell patch-clamp recordings from perirhinal pyramidal neurons and GABAergic interneurons of GAD67-GFP + mice, we found, for the first time, that the majority of PRC neurons are resonant at their resting potential, with a resonance frequency of 0.5-1.5 Hz at 23°C and of 1.5-2.8 Hz at 36°C. In the presence of ZD7288 (blocker of HCN channels) resonance was abolished in both pyramidal neurons and interneurons, suggesting that I h current is critically involved in resonance generation. Otherwise, application of TTx (voltage-dependent Na + channel blocker) attenuates the resonance in pyramidal neurons but not in interneurons, suggesting that only in pyramidal neurons the persistent sodium current has an amplifying effect. These experimental results have also been confirmed by a computational model. From a functional point of view, the resonance in the PRC would affect the reverberating activity between neocortex and hippocampus, especially during slow wave sleep, and could be involved in the redistribution and strengthening of memory representation in cortical regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Binini, Talpo, Spaiardi, Maniezzi, Pedrazzoli, Raffin, Mattiello, Castagno, Masetto, Yanagawa, Dickson, Ramat, Toselli and Biella.)

Individual variability in diurnal preference or chronotype is commonly assessed with self-report scales such as the widely used morningness-eveningness questionnaire (MEQ). We sought to investigate the MEQ's internal consistency by applying exploratory factor analysis (EFA) to determine the number of underlying latent factors in four different adult samples, two each from the United Kingdom and Brazil (total N = 3,457). We focused on factors that were apparent in all samples, irrespective of particular sociocultural diversity and geographical characteristics, so as to show a common core reproducible structure across samples. Results showed a three-factor solution with acceptable to good model fit indexes in all studied populations. Twelve of the 19 MEQ items in the three-correlated factor solution loaded onto the same factors across the four samples. This shows that the scale measures three distinguishable, yet correlated constructs: (1) items related to how people feel in the morning, which we termed efficiency of dissipation of sleep pressure (recovery process) (items 1, 3, 4, 5, 7, 9, 13, and 19); (2) items related to how people feel before sleep, which we called sensitivity to buildup of sleep pressure (items 2, 10, and 12); and (3) peak time of cognitive arousal (item 11). Although the third factor was not regarded as consistent since only one item was common among all samples, it might represent subjective amplitude. These results suggested that the latent constructs of the MEQ reflect dissociable homeostatic processes in addition to a less consistent propensity for cognitive arousal at different times of the day. By analyzing answers to MEQ items that compose these latent factors, it may be possible to extract further knowledge of factors that affect morningness-eveningness.

Background: The most advanced disease-modifying therapies (DMTs) in development for Huntington's disease (HD) require intrathecal (IT) administration, which may create or exacerbate bottlenecks in resource capacity., Objective: To understand the readiness of healthcare systems for intrathecally administered HD DMTs in terms of resource capacity dynamics and implications for patients' access to treatment., Methods: Forty HD centres across 12 countries were included. Qualitative and quantitative data on current capacity in HD centres and anticipated capacity needs following availability of a DMT were gathered via interviews with healthcare professionals (HCPs). Data modelling was used to estimate the current capacity gap in HD centres., Results: From interviews with 218 HCPs, 25% of HD centres are estimated to have the three components required for IT administration (proceduralists, nurses and facilities). On average, 114 patients per centre per year are anticipated to receive intrathecally administered DMTs in the future. At current capacity, six of the sampled centres are estimated to be able to deliver DMTs to all the anticipated patients based on current resources. The estimated waiting time for IT administration at current capacity will average 60 months (5 years) by the second year after DMT availability., Conclusion: Additional resources are needed in HD centres for future DMTs to be accessible to all anticipated patients. Timely collaboration by the HD community will be needed to address capacity gaps. Healthcare policymakers and payers will need to address costs and navigate challenges arising from country- or region-specific healthcare delivery schemes.

Approaches utilizing multiple analysis techniques on a single sample are highly desirable in research, especially to reduce the number of animals and obtain the maximum information. Golgi-Cox staining is a widely used method for characterizing axon and dendritic morphology and several attempts to combine this technique with immunofluorescence and transmission electron microscopy have been proposed. With few exceptions, most of the protocols were characterized by a high degree of complexity and low reproducibility. Here we show a simplified procedure of perfusion, fixation and staining of brain tissues that allows Golgi-Cox staining, immunofluorescence and transmission electron microscopy in the same sample, to obtain high-quality images with a low-cost procedure. The main novelty in this protocol is the possibility of performing Golgi-Cox staining after the perfusion and post-fixation of brain tissue with a buffered solution containing, not only formaldehyde, but also glutaraldehyde. This renders the tissue suitable for electron microscopy, but it is also compatible with immunofluorescence staining. This combined protocol can be used in most neuroscience laboratories as it does not require special equipment and skills. This protocol will be useful in a broad range of neuroscience topics to study morphological changes during brain development and plasticity in physiological and pathological conditions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The parent study was a survey in 28 headache centers (6 countries) which identified five potential root causes for long waiting lists that limit patient access to specialist care. Here we performed an extension of the parent study to increase the panel of centers contacted, the representativeness of the analysis, and the statistical validity of the results, and to explore the role of dedicated headache clinics, triage, and specialized nurses., Methods: We conducted a 19-question survey using a sample of 239 headache centers (16 countries). The five-area framework identified in the parent study was confirmed and further developed by describing treatment center archetypes according to their setting (general neurology versus dedicated clinic) and resources available within the center (number of healthcare professional [HCPs] full-time-equivalent positions)., Results: In total, 474 HCPs were interviewed across 16 countries. The proportion of patients with chronic migraine and episodic migraine varied across centers and countries. There was limited access to specialized centers in this enlarged sample; with global average waiting list of 3.7 months for the first visit and 2.5 months for the follow-up visit. Long waiting lists for headache patient care is a major issue in several countries, with the waiting lists for new patient visits extending up to 14 months. The presence of a dedicated nurse was correlated positively with the use of triage for prioritization of patient access (correlation coefficient: 0.85) and completing migraine diary (0.71)., Conclusion: This study confirmed differences across treatment center archetypes in terms of patients, waiting lists, level of delegation to nurse, and patient education and compliance, and provides support for the potential benefit of dedicated clinical settings for headache patients. The survey highlighted the potential role of nurses in patient education and waiting list prioritization, consequently benefiting headache centers.

Studying communities at different stages of urbanisation and industrialisation can teach us how timing and intensity of light affect the circadian clock under real-life conditions. We have previously described a strong tendency towards morningness in the Baependi Heart Study, located in a small rural town in Brazil. Here, we tested the hypothesis that this morningness tendency is associated with early circadian phase based on objective measurements (as determined by dim light melatonin onset, DLMO, and activity) and light exposure. We also analysed how well the previously collected chronotype questionnaire data were able to predict these DLMO values. The average DLMO observed in 73 participants (40 female) was 20:03 ± 01:21, SD, with an earlier average onset in men (19:38 ± 01:16) than in women (20:24 ± 01:21; P ≤ .01). However, men presented larger phase angle between DLMO and sleep onset time as measured by actigraphy (4.11 hours vs 3.16 hours; P ≤ .01). Correlational analysis indicated associations between light exposure, activity rhythms and DLMO, such that early DLMO was observed in participants with higher exposure to light, higher activity and earlier light exposure. The strongest significant predictor of DLMO was morningness-eveningness questionnaire (MEQ) (beta=-0.35, P ≤ .05), followed by age (beta = -0.47, P ≤ .01). Sex, light exposure and variables derived from the Munich chronotype questionnaire were not significant predictors. Our observations demonstrate that both early sleep patterns and earlier circadian phase have been retained in this small rural town in spite of availability of electrification, in contrast to metropolitan postindustrial areas., (© 2020 The Authors. Journal of Pineal Research published by John Wiley & Sons Ltd.)

Context: Metabolic syndrome (MetS) is a complex condition comprising a 'clustering' of components representing cardiometabolic risk factors for heart disease and diabetes; its prevalence rate is high and consequences serious. Evidence suggests that light exposure patterns and misalignment of circadian rhythms might contribute to MetS etiology by impacting energy metabolism and glucose regulation., Objective: We hypothesised that individuals with MetS would show disrupted circadian and sleep parameters alongside differences in light exposure profiles. We investigated this using data from a cohort study in Brazil., Methods: Data from 103 individuals from the Baependi Heart Cohort Study aged between 50 and 70 were analysed. Motor activity and light exposure were measured using wrist-worn actigraphy devices. Cardiometabolic data were used to calculate the number of MetS components present in each participant, and participants grouped as MetS/non-MetS according to standard guidelines. Between-group comparisons were made for the actigraphy measures; additionally, correlation analyses were conducted., Results: Motor activity and circadian profiles showed no differences between groups. However, the MetS group presented lower light exposure during the day and higher light exposure at night. Correlation analyses, including all participants, showed that greater daytime light exposure and greater light exposure difference between day and night were associated with reduced MetS risk (a lower number of MetS components). Also, the light exposure difference between day and night correlated with body mass index across all participants., Conclusions: The observed results suggest a direct association between light exposure and MetS which appears to not be attributable to disruptions in circadian activity rhythm nor to sleep parameters. This link between light exposure patterns and MetS risk could inform possible prevention strategies., Competing Interests: The authors have declared that no competing interests exist.

The critical role of neuroinflammation in favoring and accelerating the pathogenic process in Alzheimer's disease (AD) increased the need to target the cerebral innate immune cells as a potential therapeutic strategy to slow down the disease progression. In this scenario, mesenchymal stem cells (MSCs) have risen considerable interest thanks to their immunomodulatory properties, which have been largely ascribed to the release of extracellular vesicles (EVs), namely exosomes and microvesicles. Indeed, the beneficial effects of MSC-EVs in regulating the inflammatory response have been reported in different AD mouse models, upon chronic intravenous or intracerebroventricular administration. In this study, we use the triple-transgenic 3xTg mice showing for the first time that the intranasal route of administration of EVs, derived from cytokine-preconditioned MSCs, was able to induce immunomodulatory and neuroprotective effects in AD. MSC-EVs reached the brain, where they dampened the activation of microglia cells and increased dendritic spine density. MSC-EVs polarized in vitro murine primary microglia toward an anti-inflammatory phenotype suggesting that the neuroprotective effects observed in transgenic mice could result from a positive modulation of the inflammatory status. The possibility to administer MSC-EVs through a noninvasive route and the demonstration of their anti-inflammatory efficacy might accelerate the chance of a translational exploitation of MSC-EVs in AD., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Glutamate is the most excitatory neurotransmitter in the central nervous system and it is involved in the initiation and maintaining of waking and rapid-eye-movement (REM) sleep. Homer proteins act in the trafficking and/or clustering of metabotropic glutamate receptors, and polymorphisms in the HOMER1 gene have been associated with phenotypes related to glutamate signaling dysregulation. In this study, we report the association of a single nucleotide polymorphism (SNP) in the HOMER1 gene (rs3822568) with specific aspects of sleep in a sample of the Brazilian population. To accomplish this, 1,042 individuals were subjected to a full-night polysomnography, and a subset of 983 subjects had rs3822568 genotyping data available. When compared with the A allele carriers, GG genotyped individuals showed higher sleep latency, lower sleep efficiency, reduced number of arousals per hour, lower apnea-hypopnea index (AHI) and lower theta spectral power. In summary, the present findings suggest that the rs3822568 polymorphism in the HOMER1 gene is associated with sleep EEG profiles and might have an impact on sleep quality and sleep structure, with potential to explain inter-individual variation in sleep homeostasis., Competing Interests: The authors have declared that no competing interests exist.

Chronic exposure to high circulating levels of glucocorticoids (GCs) may be a key risk factor for Alzheimer's Disease (AD) development and progression. In addition, hyper-activation of glucocorticoid receptors (GRs) induces brain alterations comparable to those produced by AD. In transgenic mouse models of AD, GCs increase the production of the most important and typical hallmarks of this dementia such as: Aβ40, Aβ42 and tau protein (both the total tau and its hyperphosphorylated isoforms). Moreover, GCs in brain are pivotal regulators of dendritic spine turnover and microglia activity, two phenomena strongly altered in AD. Although it is well-established that GCs primes the neuroinflammatory response in the brain to some stimuli, it is unknown whether or how GRs modulates dendritic spine plasticity and microglia activity in AD. In this study, we evaluated, using combined Golgi Cox and immunofluorescence techniques, the role of GR agonists and antagonists on dendritic spine plasticity and microglia activation in hippocampus of 3xTg-AD mice. We found that dexamethasone, an agonist of GRs, was able to significantly reduce dendritic spine density and induced proliferation and activation of microglia in CA1 region of hippocampus of 3xTg-AD mice at 6 and 10 months of age. On the contrary, the treatment with mifepristone, an antagonist of GRs, strongly enhanced dendritic spine density, decreased microglia density and improved the behavioural performance of 3xTg-AD mice. Additionally, primary microglial cells in vitro were directly activated by dexamethasone. Together, these data demonstrate that stress exacerbates AD and promotes a rapid progression of the pathology acting on both neurons and glial cells, supporting an important pro-inflammatory role of GC within CNS in AD. Consequently, these results further strengthen the need to test clinical interventions that correct GCs dysregulation as promising therapeutic strategy to delay the onset and slow down the progression of AD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We evaluated the circadian pattern of variation of the descending pain modulatory system (DPMS) using a conditioned pain modulation (CPM) paradigm according to the variable-number tandem-repeat (VNTR) of the clock gene PER3 polymorphism. We assessed the relationship between the genotypes PER3 4/4 and PER3 5/5 and the temporal pattern of variation across the day using the following measures: the heat pain threshold (HPT), the cold pressure test (CPT), and the serum levels of BDNF and S100-B protein. The ∆-values (from afternoon to morning) of these measures were used for the analysis. The circadian phenotype was according to the mid-point sleep time established by the Munich ChronoType Questionnaire (MCTQ). We included 18 healthy volunteers (15 women) ages 18 to 30. A Generalized Linear Model (GLM) revealed a significant difference in the ∆-CPM-task between Per3 4/4 and Per3 5/5 genotypes, with means (SDs) of -0.41 (0.78) vs. 0.67 (0.90) (χ 2  = 7.256; df = 1' P = 0.007), respectively. Both sleep deprivation of at least 2 h/day (B = -0.96, 95% confidence interval (CI) = -1.86 to -0.11)) and the ∆-S100-B protein (-0.03, 95% CI = -0.06 to -0.02) were negatively correlated with the ∆-CPM-task, while the ∆-BDNF was positively correlated with the ∆-CPM-task (0.015, 95% CI = 0.01 to 0.03). We observed a difference in the ∆-CPT between PER3 4/4 and PER3 5/5 (0.11 (4.51) vs. 4.00 (2.60), respectively) (χ 2  = 22.251; df = 1 P = 0.001). These findings suggest that the polymorphism of PER3 5/5 is associated with a decrease in the inhibitory function of the DPMS over the course of the day. However, sleep deprivation is an independent factor that also reduces the inhibitory function of the DPMS, regardless of the PER3 VNTR polymorphism.

Objectives: We searched for interactions between PER3 gene VNTR polymorphism, latitude, sleep duration, diurnal sleepiness, and social jetlag., Design: We selected samples from 3 distinct cities along the latitudinal range of Brazil and comprising the same time zone., Setting: Undergraduate universities located in 3 major cities of Brazil., Participants: A total of 980 undergraduate students: 276 from Maceio (latitude 9°), 358 from Campinas (latitude 22°), and 346 from Porto Alegre (latitude 30°)., Measurements: PER3 variable number of tandem repeats genotyping, diurnal sleepiness, sleep duration (weekdays and weekend), chronotype, and social jetlag., Results: Latitude is associated with a differential expression of circadian and sleep profiles. We observed a shift toward eveningness with increased latitude and increased social jetlag and diurnal sleepiness at latitude 30°. Moreover, our results suggest that the PER3 variable number of tandem repeats polymorphism has a modulatory effect on these circadian and sleep profiles: the variant PER3 4/4 is associated with a smaller difference in the sleep duration on weekdays among different latitudes and is associated with longer sleep duration on weekends just at latitude 30°, even when compared to both other genotypes at the same latitude. On the other hand, irrespective of the genotype, volunteers from latitude 30° expressed increased social jetlag and diurnal sleepiness., Conclusions: The seasonal variation in the light/dark cycle, tied to latitude, together with the tight social time constraints that young adults are subjected to during weekdays, generates differences in the sleep phenotypes. Volunteers with the PER3 4/4 variant who live farther from the equator have a greater increase in their weekend sleep duration., (Copyright © 2018 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Natural daylight exposures in arctic regions vary substantially across seasons. Negative consequences have been observed in self-reports of sleep and daytime functions during the winter but have rarely been studied in detail. The focus of the present study set out to investigate sleep seasonality among indoor workers using objective and subjective measures. Sleep seasonality among daytime office workers ( n = 32) in Kiruna (Sweden, 67.86° N, 20.23° E) was studied by comparing the same group of workers in a winter and summer week, including work and days off at the weekend, using actigraphs (motion loggers) and subjective ratings of alertness and mood. Actigraph analyses showed delayed sleep onset of 39 min in winter compared to the corresponding summer week ( p < 0.0001) and shorter weekly sleep duration by 12 min ( p = 0.0154). A delay of mid-sleep was present in winter at workdays (25 min, p < 0.0001) and more strongly delayed during days off (46 min, p < 0.0001). Sleepiness levels were higher in winter compared to summer ( p < 0.05). Increased morning light exposure was associated with earlier mid-sleep ( p < 0.001), while increased evening light exposure was associated with delay ( p < 0.01). This study confirms earlier work that suggests that lack of natural daylight delays the sleep/wake cycle in a group of indoor workers, despite having access to electric lighting. Photic stimuli resulted in a general advanced sleep/wake rhythm during summer and increased alertness levels., Competing Interests: Conflicts of InterestThe authors declare no conflict of interest., (© 2018 by the authors.)