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We read with interest the commentary by Skeldon and Dijk about our article "Weekly, seasonal and chronotype-dependent variation of dim light melatonin onset." The discussion points raised by Skeldon and Dijk are currently among the most hotly debated in human circadian science. What external factors determine human phase of entrainment? How great is the contribution of natural versus artificial light and sun time versus social time? Our intra-individual data add to the still limited evidence from field studies in this matter. In their commentary, Skeldon and Dijk formulate two either-or hypotheses, postulating that humans entrain either solely to the natural light-dark cycle (sun time referenced by midday) (H1 ) or solely to the light selected by local clock time and social constraints (H2 ). Neither hypothesis accounts for the effect of season on human light exposure. We interpreted our findings along more complex lines, speculating that the 1-h earlier melatonin rise in summer found in our sample is likely the combined result of daylight saving time (DST)-induced behavioral advances and a stronger natural zeitgeber in summer (light exposure determined by social and seasonal factors, Horiginal ). Here, we show how the criticism by Skeldon and Dijk is based on two sentences quoted out of context (misrepresenting our hypothesis as H1 ) and that their hypothesis H2 leaves out important seasonal components in light exposure.
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Melatonina , Ritmo Circadiano , Humanos , Luz , Fotoperíodo , Estações do Ano , SonoRESUMO
Periods of sleep and wakefulness can be estimated from wrist-locomotor activity recordings via algorithms that identify periods of relative activity and inactivity. Here, we evaluated the performance of our Munich Actimetry Sleep Detection Algorithm. The Munich Actimetry Sleep Detection Algorithm uses a moving 24-h threshold and correlation procedure estimating relatively consolidated periods of sleep and wake. The Munich Actimetry Sleep Detection Algorithm was validated against sleep logs and polysomnography. Sleep-log validation was performed on two field samples collected over 54 and 34 days (median) in 34 adolescents and 28 young adults. Polysomnographic validation was performed on a clinical sample of 23 individuals undergoing one night of polysomnography. Epoch-by-epoch analyses were conducted and comparisons of sleep measures carried out via Bland-Altman plots and correlations. Compared with sleep logs, the Munich Actimetry Sleep Detection Algorithm classified sleep with a median sensitivity of 80% (interquartile range [IQR] = 75%-86%) and specificity of 91% (87%-92%). Mean onset and offset times were highly correlated (r = .86-.91). Compared with polysomnography, the Munich Actimetry Sleep Detection Algorithm reached a median sensitivity of 92% (85%-100%) but low specificity of 33% (10%-98%), owing to the low frequency of wake episodes in the night-time polysomnographic recordings. The Munich Actimetry Sleep Detection Algorithm overestimated sleep onset (~21 min) and underestimated wake after sleep onset (~26 min), while not performing systematically differently from polysomnography in other sleep parameters. These results demonstrate the validity of the Munich Actimetry Sleep Detection Algorithm in faithfully estimating sleep-wake patterns in field studies. With its good performance across daytime and night-time, it enables analyses of sleep-wake patterns in long recordings performed to assess circadian and sleep regularity and is therefore an excellent objective alternative to sleep logs in field settings.
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Actigrafia , Sono , Adolescente , Algoritmos , Humanos , Polissonografia , Reprodutibilidade dos Testes , Vigília , Adulto JovemRESUMO
In humans, the most important zeitgeber for entrainment is light. Laboratory studies have shown that meaningful changes in light exposure lead to phase shifts in markers of the circadian clock. In natural settings, light is a complex signal varying with external conditions and individual behaviors; nonetheless, phase of entrainment is assumed to be fairly stable. Here, we investigated the influence of season and weekly schedule (as indicators of variation in light landscapes) on phase of entrainment. Using a within-subjects design (N = 33), we assessed dim-light melatonin onset (DLMO) as a circadian phase marker in humans, on workdays and work-free days, in summer (under daylight saving time) and in winter, while also estimating sleep times from actimetry. Our mixed-model regressions show that both season and weekly structure are linked with changes in phase of entrainment and sleep. In summer, both DLMO and sleep times were about 1 hour earlier compared to winter, and sleep duration was shorter. On work-free days, DLMO and sleep times were later, and their phase relationship differed more relative to workdays. All these effects were stronger in later chronotypes (those who habitually sleep late). Our results confirm that phase of entrainment is earlier when stronger zeitgebers are present (summer) and show that it relates to midday or midnight rather than sunrise or sunset. Additionally, they suggest that late chronotypes are capable of rapid phase shifts each week as they move between workdays and work-free days, stimulating interesting questions about the stability of circadian phase under natural conditions.
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Ritmo Circadiano/efeitos dos fármacos , Luz , Melatonina/metabolismo , Admissão e Escalonamento de Pessoal , Glândula Pineal/efeitos dos fármacos , Estações do Ano , Sono/efeitos da radiação , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Estudos Longitudinais , Masculino , Glândula Pineal/metabolismo , Saliva/metabolismo , Fatores de Tempo , Adulto JovemRESUMO
Following general anesthesia, people are often confused about the time of day and experience sleep disruption and fatigue. It has been hypothesized that these symptoms may be caused by general anesthesia affecting the circadian clock. The circadian clock is fundamental to our well-being because it regulates almost all aspects of our daily biochemistry, physiology, and behavior. Here, we investigated the effects of the most common general anesthetic, isoflurane, on time perception and the circadian clock using the honeybee (Apis mellifera) as a model. A 6-h daytime anesthetic systematically altered the time-compensated sun compass orientation of the bees, with a mean anticlockwise shift in vanishing bearing of 87° in the Southern Hemisphere and a clockwise shift in flight direction of 58° in the Northern Hemisphere. Using the same 6-h anesthetic treatment, time-trained bees showed a delay in the start of foraging of 3.3 h, and whole-hive locomotor-activity rhythms were delayed by an average of 4.3 h. We show that these effects are all attributable to a phase delay in the core molecular clockwork. mRNA oscillations of the central clock genes cryptochrome-m and period were delayed by 4.9 and 4.3 h, respectively. However, this effect is dependent on the time of day of administration, as is common for clock effects, and nighttime anesthesia did not shift the clock. Taken together, our results suggest that general anesthesia during the day causes a persistent and marked shift of the clock effectively inducing "jet lag" and causing impaired time perception. Managing this effect in humans is likely to help expedite postoperative recovery.
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Anestesia Geral/efeitos adversos , Abelhas/fisiologia , Relógios Circadianos/fisiologia , Percepção do Tempo/fisiologia , Ciclos de Atividade/efeitos dos fármacos , Ciclos de Atividade/fisiologia , Anestésicos Gerais/efeitos adversos , Animais , Sequência de Bases , Abelhas/efeitos dos fármacos , Abelhas/genética , Relógios Circadianos/efeitos dos fármacos , Relógios Circadianos/genética , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Voo Animal/efeitos dos fármacos , Voo Animal/fisiologia , Genes de Insetos , Humanos , Isoflurano/efeitos adversos , Modelos Animais , Fotoperíodo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Percepção do Tempo/efeitos dos fármacosRESUMO
Earlier human activity relative to sunrise and sunset, the very essence of daylight saving time, is linked with health and safety detriments in humans. A new study predicts that deer, at least, may benefit from earlier human activity through reduced deer-vehicle collisions.
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Cervos , Animais , Humanos , Tempo , Estações do AnoRESUMO
Early school times clash with the late sleep of adolescents, leading to wide-spread sleep restriction in students. Evidence suggests that delaying school starts is beneficial for sleep and recent studies investigated whether this also translates into improved academic achievement. We thus conducted a systematic review of the literature on school start times, grades and test scores in middle and high-school students. We reviewed 21 studies following the PRISMA guidelines and assessed the evidence quality using a pre-defined risk of bias tool. Nine studies reported no association of later starts with achievement, while the remaining reported mixed (5), positive (5), negative (1) or unclear (1) results. Considering the heterogeneity in academic outcomes, study types, amount of delay and exposure, and the substantial risk of bias, a meta-analysis was not warranted - instead we provide grouped reviews and discussion. Overall, no generalisable improvements in achievement with later starts emerge beyond the level of single studies. This does not necessarily preclude improvements in students' learning but highlights shortcomings of the literature and the challenges of using grades and test scores to operationalise academic achievement. Given other previously reported positive outcomes, our results suggest that schools could start later while achievement is likely maintained.
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Sucesso Acadêmico , Logro , Adolescente , Escolaridade , Humanos , Instituições Acadêmicas , Sono , EstudantesRESUMO
The mismatch between teenagers' late sleep phase and early school start times results in acute and chronic sleep reductions. This is not only harmful for learning but may reduce career prospects and widen social inequalities. Delaying school start times has been shown to improve sleep at least short-term but whether this translates to better achievement is unresolved. Here, we studied whether 0.5-1.5 years of exposure to a flexible school start system, with the daily choice of an 8 AM or 8:50 AM-start, allowed secondary school students (n = 63-157, 14-21 years) to improve their quarterly school grades in a 4-year longitudinal pre-post design. We investigated whether sleep, changes in sleep or frequency of later starts predicted grade improvements. Mixed model regressions with 5111-16,724 official grades as outcomes did not indicate grade improvements in the flexible system per se or with observed sleep variables nor their changes-the covariates academic quarter, discipline and grade level had a greater effect in our sample. Importantly, our finding that intermittent sleep benefits did not translate into detectable grade changes does not preclude improvements in learning and cognition in our sample. However, it highlights that grades are likely suboptimal to evaluate timetabling interventions despite their importance for future success.
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Early school times fundamentally clash with the late sleep of teenagers. This mismatch results in chronic sleep deprivation posing acute and long-term health risks and impairing students' learning. Despite immediate short-term benefits for sleep, the long-term effects of later starts remain unresolved. In a pre-post design over 1 year, we studied a unique flexible school start system, in which 10-12th grade students chose daily between an 8:00 or 8:50AM-start. Missed study time (8:00-8:50) was compensated for during gap periods or after classes. Based on 2 waves (6-9 weeks of sleep diary each), we found that students maintained their ~ 1-h-sleep gain on later days, longitudinally (n = 28) and cross-sectionally (n = 79). This gain was independent of chronotype and frequency of later starts but attenuated for boys after 1 year. Students showed persistently better sleep quality and reduced alarm-driven waking and reported psychological benefits (n = 93) like improved motivation, concentration, and study quality on later days. Nonetheless, students chose later starts only infrequently (median 2 days/week), precluding detectable sleep extensions in the flexible system overall. Reasons for not choosing late starts were the need to make up lost study time, preference for extra study time and transport issues. Whether flexible systems constitute an appealing alternative to fixed delays given possible circadian and psychological advantages warrants further investigation.
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Ritmo Circadiano/fisiologia , Privação do Sono/psicologia , Sono/fisiologia , Adolescente/fisiologia , Adulto , Escolaridade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Fatores de Risco , Instituições Acadêmicas , Privação do Sono/epidemiologia , Privação do Sono/fisiopatologia , Estudantes/psicologia , Fatores de Tempo , Adulto JovemRESUMO
With the emergence of big data science, the question how we can easily collect meaningful information about circadian clock phenotypes in large human cohorts imposes itself. Here, we describe potentials and limitations of using questionnaires, specifically the Munich ChronoType Questionnaire (MCTQ), to characterize such circadian phenotypes. We also discuss scenarios when alternative methods might be more appropriate.
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Ritmo Circadiano , Fenótipo , Inquéritos e Questionários/normas , Big Data , HumanosRESUMO
The integrity of extracted ribonucleic acid (RNA) is commonly assessed by gel electrophoresis and subsequent analysis of the ribosomal RNA (rRNA) bands. Using the honey bee, Apis mellifera (Hymenoptera: Apidae), as an example, the electrophoretic rRNA profile of insects is explained. This profile differs significantly from the standard benchmark since the 28S rRNA of most insects contains an endogenous "hidden break." Upon denaturation, the masking hydrogen bonds are disrupted, releasing two similar sized fragments that both migrate closely with 18S rRNA. The resulting rRNA profile thus reflects the endogenous composition of insect rRNA and should not be misinterpreted as degradation.
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Abelhas/genética , Conformação de Ácido Nucleico , RNA Ribossômico/química , Animais , Eletroforese/normas , Ligação de HidrogênioRESUMO
Sleep deprivation in teenage students is pervasive and a public health concern, but evidence is accumulating that delaying school start times may be an effective countermeasure. Most studies so far assessed static changes in schools start time, using cross-sectional comparisons and one-off sleep measures. When a high school in Germany introduced flexible start times for their senior students-allowing them to choose daily between an 8 am or 9 am start (≥08:50)-we monitored students' sleep longitudinally using subjective and objective measures. Students (10-12th grade, 14-19 y) were followed 3 weeks prior and 6 weeks into the flexible system via daily sleep diaries (nâ =â 65) and a subcohort via continuous wrist-actimetry (nâ =â 37). Satisfaction and perceived cognitive outcomes were surveyed at study end. Comparisons between 8 am and ≥9 am-starts within the flexible system demonstrated that students slept 1.1 h longer when starting school later-independent of gender, grade, chronotype, and frequency of later starts; sleep offsets were delayed but, importantly, onsets remained unchanged. Sleep quality was increased and alarm-driven waking reduced. However, overall sleep duration in the flexible system was not extended compared to baseline-likely because students did not start later frequently enough. Nonetheless, students were highly satisfied with the flexible system and reported cognitive and sleep improvements. Therefore, flexible systems may present a viable alternative for implementing later school starts to improve teenage sleep if students can be encouraged to use the late-option frequently enough. Flexibility may increase acceptance of school start changes and speculatively even prevent delays in sleep onsets through occasional early starts.
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Instituições Acadêmicas , Sono , Adolescente , Estudos Transversais , Alemanha , Humanos , Fatores de TempoRESUMO
BACKGROUND: Melatonin modulates circadian rhythms in physiology and sleep initiation. Genetic variants of the MTNR1B locus, encoding the melatonin MT2 receptor, have been associated with increased type 2 diabetes (T2D) risk. Carriers of the common intronic MTNR1B rs10830963 T2D risk variant have modified sleep and circadian traits such as changes of the melatonin profile. However, it is currently unknown whether rare variants in the MT2 coding region are also associated with altered sleep and circadian phenotypes, including meal timing. MATERIALS AND METHODS: In this pilot study, 28 individuals [50% male; 46-82 years old; 50% with rare MT2 mutations (T2D MT2)] wore actigraphy devices and filled out daily food logs for 4 weeks. We computed circadian, sleep, and caloric intake phenotypes, including sleep duration, timing, and regularity [assessed by the Sleep Regularity Index (SRI)]; composite phase deviations (CPD) as well a sleep timing-based proxy for circadian misalignment; and caloric intake patterns throughout the day. Using regression analyses, we estimated age- and sex-adjusted mean differences (MD) and 95% confidence intervals (95%CI) between the two patient groups. Secondary analyses also compare T2D MT2 to 15 healthy controls. RESULTS: Patients with rare MT2 mutations had a later sleep onset (MD = 1.23, 95%CI = 0.42;2.04), and midsleep time (MD = 0.91, 95%CI = 0.12;1.70), slept more irregularly (MD in SRI = -8.98, 95%CI = -16.36;-1.60), had higher levels of behavioral circadian misalignment (MD in CPD = 1.21, 95%CI = 0.51;1.92), were more variable in regard to duration between first caloric intake and average sleep offset (MD = 1.08, 95%CI = 0.07;2.08), and had more caloric episodes in a 24 h day (MD = 1.08, 95%CI = 0.26;1.90), in comparison to T2D controls. Secondary analyses showed similar patterns between T2D MT2 and non-diabetic controls. CONCLUSION: This pilot study suggests that compared to diabetic controls, T2D MT2 patients display a number of adverse sleep, circadian, and caloric intake phenotypes, including more irregular behavioral timing. A prospective study is needed to determine the role of these behavioral phenotypes in T2D onset and severity, especially in view of rare MT2 mutations.
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Individuals vary in how their circadian system synchronizes with the cyclic environment (zeitgeber). Assessing these differences in "phase of entrainment"-often referred to as chronotype-is an important procedure in laboratory experiments and epidemiological studies but is also increasingly applied in circadian medicine, both in diagnosis and therapy. While biochemical measurements (e.g., dim-light melatonin onset [DLMO]) of internal time are still the gold standard, they are laborious, expensive, and mostly rely on special conditions (e.g., dim light). Chronotype estimation in the form of questionnaires is useful in approximating the timing of an individual's circadian clock. They are simple, inexpensive, and location independent (e.g., administrable on- and offline) and can therefore be easily administered to many individuals. The Munich ChronoType Questionnaire (MCTQ) is an established instrument to assess chronotype by asking subjects about their sleep-wake-behavior. Here we present a shortened version of the MCTQ, the µMCTQ, for use in situations in which instrument length is critical, such as in large cohort studies. The µMCTQ contains only the core chronotype module of the standard MCTQ (stdMCTQ), which was shortened and adapted from 17 to 6 essential questions, allowing for a quick assessment of chronotype and other related parameters such as social jetlag and sleep duration. µMCTQ results correspond well to the ones collected by the stdMCTQ and are externally validated by actimetry and DLMO, assessed at home (no measure of compliance). Sleep onset, midpoint of sleep, and the µMCTQ-derived marker of chronotype showed slight deviations toward earlier times in the µMCTQ when compared with the stdMCTQ (<35 min). The µMCTQ assessment of chronotype showed good test-retest reliability and correlated significantly with phase markers from actimetry and melatonin (DLMO), especially with measurements taken on work-free days. Because of its brevity, the µMCTQ represents an ideal tool to estimate individual internal time in time-critical contexts, from large cohort studies to individualized medicine.
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Relógios Circadianos , Ritmo Circadiano , Sono , Inquéritos e Questionários/normas , Vigília , Actigrafia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores de Tempo , Adulto JovemRESUMO
Many regions and countries are reconsidering their use of Daylight Saving Time (DST) but their approaches differ. Some, like Japan, that have not used DST over the past decades are thinking about introducing this twice-a-year change in clock time, while others want to abolish the switch between DST and Standard Time, but don't agree which to use: California has proposed keeping perennial DST (i.e., all year round), and the EU debates between perennial Standard Time and perennial DST. Related to the discussion about DST is the discussion to which time zone a country, state or region should belong: the state of Massachusetts in the United States is considering switching to Atlantic Standard Time, i.e., moving the timing of its social clock (local time) 1 h further east (which is equivalent to perennial DST), and Spain is considering leaving the Central European Time to join Greenwich Mean Time (GMT), i.e., moving its social timing 1 h further west. A wave of DST discussions seems to periodically sweep across the world. Although DST has always been a political issue, we need to discuss the biology associated with these decisions because the circadian clock plays a crucial role in how the outcome of these discussions potentially impacts our health and performance. Here, we give the necessary background to understand how the circadian clock, the social clock, the sun clock, time zones, and DST interact. We address numerous fallacies that are propagated by lay people, politicians, and scientists, and we make suggestions of how problems associated with DST and time-zones can be solved based on circadian biology.
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The Munich ChronoType Questionnaire (MCTQ) has now been available for more than 15 years and its original publication has been cited 1240 times (Google Scholar, May 2019). Additionally, its online version, which was available until July 2017, produced almost 300,000 entries from all over the world (MCTQ database). The MCTQ has gone through several versions, has been translated into 13 languages, and has been validated against other more objective measures of daily timing in several independent studies. Besides being used as a method to correlate circadian features of human biology with other factors-ranging from health issues to geographical factors-the MCTQ gave rise to the quantification of old wisdoms, like "teenagers are late", and has produced new concepts, like social jetlag. Some like the MCTQ's simplicity and some view it critically. Therefore, it is time to present a self-critical view on the MCTQ, to address some misunderstandings, and give some definitions of the MCTQ-derived chronotype and the concept of social jetlag.
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[This corrects the article DOI: 10.3389/fphys.2019.00944.].
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Local and national governments around the world are currently considering the elimination of the annual switch to and from Daylight Saving Time (DST). As an international organization of scientists dedicated to studying circadian and other biological rhythms, the Society for Research on Biological Rhythms (SRBR) engaged experts in the field to write a Position Paper on the consequences of choosing to live on DST or Standard Time (ST). The authors take the position that, based on comparisons of large populations living in DST or ST or on western versus eastern edges of time zones, the advantages of permanent ST outweigh switching to DST annually or permanently. Four peer reviewers provided expert critiques of the initial submission, and the SRBR Executive Board approved the revised manuscript as a Position Paper to help educate the public in their evaluation of current legislative actions to end DST.
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Ritmo Circadiano , Luz , Fotoperíodo , Humanos , Estações do Ano , Sistema Solar , Fatores de TempoRESUMO
Our lives are structured by the daily alternation of activity and rest, of wake and sleep. Despite significant advances in circadian and sleep research, we still lack answers to many of the most fundamental questions about this conspicuous behavioral pattern. We strongly believe that investigating this pattern in entrained conditions, real-life and daily contexts-in situ-will help the field to elucidate some of these central questions. Here, we present two common approaches for in situ investigation of human activity and rest: the Munich ChronoType Questionnaire (MCTQ) and actimetry. In the first half of this chapter, we provide detailed instructions on how to use and interpret the MCTQ. In addition, we give an overview of the main insights gained with this instrument over the past 10 years, including some new findings on the interaction of light and age on sleep timing. In the second half of this chapter, we introduce the reader to the method of actimetry and share our experience in basic analysis techniques, including visualization, smoothing, and cosine model fitting of in situ recorded data. Additionally, we describe our new approach to automatically detect sleep from activity recordings. Our vision is that the broad use of such easy techniques in real-life settings combined with automated analyses will lead to the creation of large databases. The resulting power of big numbers will promote our understanding of such fundamental biological phenomena as sleep.