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Circadian clock function declines with ageing, which can aggravate ageing-related diseases such as type 2 diabetes and neurodegenerative disorders. Understanding age-related changes in the circadian system at a systemic level can contribute to the development of strategies to promote healthy ageing. The goal of this study was to investigate the impact of ageing on 24-h rhythms in amine metabolites across four tissues in young (2 months of age) and old (22-25 months of age) mice using a targeted metabolomics approach. Liver, plasma, the suprachiasmatic nucleus (SCN; the location of the central circadian clock in the hypothalamus) and the paraventricular nucleus (PVN; a downstream target of the SCN) were collected from young and old mice every 4 h during a 24-h period (n = 6-7 mice per group). Differential rhythmicity analysis revealed that ageing impacts 24-h rhythms in the amine metabolome in a tissue-specific manner. Most profound changes were observed in the liver, in which rhythmicity was lost in 60% of the metabolites in aged mice. Furthermore, we found strong correlations in metabolite levels between the liver and plasma and between the SCN and the PVN in young mice. These correlations were almost completely abolished in old mice. These results indicate that ageing is accompanied by a severe loss of the circadian coordination between tissues and by disturbed rhythmicity of metabolic processes. The tissue-specific impact of ageing may help to differentiate mechanisms of ageing-related disorders in the brain versus peripheral tissues and thereby contribute to the development of potential therapies for these disorders.
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Envejecimiento , Ritmo Circadiano , Hígado , Metaboloma , Núcleo Hipotalámico Paraventricular , Núcleo Supraquiasmático , Animales , Envejecimiento/metabolismo , Envejecimiento/fisiología , Núcleo Supraquiasmático/metabolismo , Ritmo Circadiano/fisiología , Ratones , Hígado/metabolismo , Masculino , Núcleo Hipotalámico Paraventricular/metabolismo , Ratones Endogámicos C57BL , Relojes Circadianos/fisiología , Aminas/metabolismoRESUMEN
Adaptation of physiology and behavior to seasonal changes in the environment are for many organisms essential for survival. Most of our knowledge about the underlying mechanisms comes from research on photoperiodic regulation of reproduction in plants, insects and mammals. However, even humans, who mostly live in environments with minimal seasonal influences, show annual rhythms in physiology (e.g., immune activity, brain function), behavior (e.g., sleep-wake cycles) and disease prevalence (e.g., infectious diseases). As seasonal variations in environmental conditions may be drastically altered due to climate change, the understanding of the mechanisms underlying seasonal adaptation of physiology and behavior becomes even more relevant. While many species have developed specific solutions for dedicated tasks of photoperiodic regulation, we find a number of common principles and mechanisms when comparing insect and mammalian systems: (1) the circadian system contributes to photoperiodic regulation; (2) similar signaling molecules (VIP and PDF) are used for transferring information from the circadian system to the neuroendocrine system controlling the photoperiodic response; (3) the hormone melatonin participates in seasonal adaptation in insects as well as mammals; and (4) changes in photoperiod affect neurotransmitter function in both animal groups. The few examples of overlap elaborated in this perspective article, as well as the discussion on relevance for humans, should be seen as encouragement to unravel the machinery of seasonal adaptation in a multitude of organisms.
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Misalignment of the daily sleep-wake and fasting-feeding cycles with the endogenous circadian timing system is an inevitable consequence of night shift work and is associated with adverse metabolic health effects. However, a detailed characterisation of the effects of night shifts on 24-h rhythms in the metabolome is missing. We performed targeted metabolomic profiling on plasma samples collected every 2 h from healthy human subjects during two 24-h measurement periods at baseline and on the fourth day of a simulated night shift protocol, in which the habitual sleep-wake cycle was delayed by 10 h. Thirty-two out of the 130 detected metabolites showed a 24-h rhythm both at baseline and during the night shift condition. Among these, 75% were driven by sleep-wake and fasting-feeding cycles rather than by the endogenous circadian clock, showing an average phase delay of 8.8 h during the night shift condition. Hence, the majority of rhythmic metabolites were misaligned relative to the endogenous circadian system during the night shift condition. This could be a key mechanism involved in the increased prevalence of adverse metabolic health effects observed in shift workers. On the individual level, the response to the night shift protocol was highly diverse, with phase shifts of rhythmic metabolite profiles ranging from a 0.2-h advance in one subject to a 12-h delay in another subject, revealing an individual metabolomic signature of circadian misalignment. Our findings provide insight into the overall and individual responses of the metabolome to circadian misalignment associated with night schedules and may thereby contribute to the development of individually tailored strategies to minimise the metabolic impacts of shift work.
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Ritmo Circadiano/fisiología , Metabolismo/fisiología , Horario de Trabajo por Turnos/efectos adversos , Adulto , Relojes Circadianos , Femenino , Voluntarios Sanos , Humanos , Iluminación , Masculino , Metaboloma , Metabolómica , Fotoperiodo , Horario de Trabajo por Turnos/psicología , Sueño/fisiologíaRESUMEN
Circadian variations of various aspects of the immune system have been described. However, the circadian control of T cells has been relatively unexplored. Here, we investigated the role of circadian clocks in regulating CD8 T cell response to antigen presentation by dendritic cells (DCs). The in vivo CD8 T cell response following vaccination with DCs loaded with the OVA257-264 peptide antigen (DC-OVA) leads to a higher expansion of OVA-specific T cells in response to vaccination done in the middle of the day, compared to other time points. This rhythm was dampened when DCs deficient for the essential clock gene Bmal1 were used and abolished in mice with a CD8 T cell-specific Bmal1 deletion. Thus, we assessed the circadian transcriptome of CD8 T cells and found an enrichment in the daytime of genes and pathways involved in T cell activation. Based on this, we investigated early T cell activation events. Three days postvaccination, we found higher T cell activation markers and related signaling pathways (including IRF4, mTOR, and AKT) after a vaccination done during the middle of the day compared to the middle of the night. Finally, the functional impact of the stronger daytime response was shown by a more efficient response to a bacterial challenge at this time of day. Altogether, these results suggest that the clock of CD8 T cells modulates the response to vaccination by shaping the transcriptional program of these cells and making them more prone to strong and efficient activation and proliferation according to the time of day.
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Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Relojes Circadianos/inmunología , Ritmo Circadiano/inmunología , Transducción de Señal , Presentación de Antígeno/inmunología , Antígenos/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Activación de Linfocitos/inmunología , Modelos Biológicos , VacunaciónRESUMEN
Misalignment of the endogenous circadian timing system leads to disruption of physiological rhythms and may contribute to the development of the deleterious health effects associated with night shift work. However, the molecular underpinnings remain to be elucidated. Here, we investigated the effect of a 4-day simulated night shift work protocol on the circadian regulation of the human transcriptome. Repeated blood samples were collected over two 24-hour measurement periods from eight healthy subjects under highly controlled laboratory conditions before and 4 days after a 10-hour delay of their habitual sleep period. RNA was extracted from peripheral blood mononuclear cells to obtain transcriptomic data. Cosinor analysis revealed a marked reduction of significantly rhythmic transcripts in the night shift condition compared with baseline at group and individual levels. Subsequent analysis using a mixed-effects model selection approach indicated that this decrease is mainly due to dampened rhythms rather than to a complete loss of rhythmicity: 73% of transcripts rhythmically expressed at baseline remained rhythmic during the night shift condition with a similar phase relative to habitual bedtimes, but with lower amplitudes. Functional analysis revealed that key biological processes are affected by the night shift protocol, most notably the natural killer cell-mediated immune response and Jun/AP1 and STAT pathways. These results show that 4 days of simulated night shifts leads to a loss in temporal coordination between the human circadian transcriptome and the external environment and impacts biological processes related to the adverse health effects associated to night shift work.
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Ritmo Circadiano/fisiología , Simulación por Computador , Leucocitos Mononucleares/metabolismo , Horario de Trabajo por Turnos , Trastornos del Sueño del Ritmo Circadiano/fisiopatología , Sueño/fisiología , Transcriptoma , Adolescente , Adulto , Femenino , Humanos , Masculino , Trastornos del Sueño del Ritmo Circadiano/genética , Adulto JovenRESUMEN
Shift work, defined as work occurring outside typical daytime working hours, is associated with an increased risk of various non-communicable diseases, including diabetes and cardiovascular disease. Disruption of the internal circadian timing system and concomitant sleep disturbances is thought to play a critical role in the development of these health problems. Indeed, controlled laboratory studies have shown that short-term circadian misalignment and sleep restriction independently impair physiological processes, including insulin sensitivity, energy expenditure, immune function, blood pressure and cardiac modulation by the autonomous nervous system. If allowed to persist, these acute effects may lead to the development of cardiometabolic diseases in the long term. Here, we discuss the evidence for the contributions of circadian disruption and associated sleep disturbances to the risk of metabolic and cardiovascular health problems in shift workers. Improving the understanding of the physiological mechanisms affected by circadian misalignment and sleep disturbance will contribute to the development and implementation of strategies that prevent or mitigate the cardiometabolic impact of shift work.
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Enfermedades Cardiovasculares , Horario de Trabajo por Turnos , Trastornos del Sueño-Vigilia , Enfermedades Cardiovasculares/epidemiología , Ritmo Circadiano , Humanos , Horario de Trabajo por Turnos/efectos adversos , Sueño , Trastornos del Sueño-Vigilia/etiologíaRESUMEN
AIM: The objective of this study was to investigate whether the pharmacokinetics of orally administered levofloxacin show 24 h variation. Levofloxacin was used as a model compound for solubility and permeability independent absorption and passive renal elimination. METHODS: In this single centre, crossover, open label study, 12 healthy subjects received an oral dose of 1000 mg levofloxacin at six different time points equally divided over the 24 h period. Population pharmacokinetic modelling was used to identify potential 24 h variation in the pharmacokinetic parameters of this drug. RESULTS: The pharmacokinetics of levofloxacin could be described by a one compartment model with first order clearance and a transit compartment to describe drug absorption. The fit of the model was significantly improved when the absorption rate constant was described as a cosine function with a fixed period of 24 h, a relative amplitude of 47% and a peak around 08.00 h in the morning. Despite this variation in absorption rate constant, simulations of a once daily dosing regimen showed that tmax , Cmax and the area under the curve at steady-state were not affected by the time of drug administration. CONCLUSION: The finding that the absorption rate constant showed considerable 24 h variation may be relevant for drugs with similar physicochemical properties as levofloxacin that have a narrower therapeutic index. Levofloxacin, however, can be dosed without taking into account the time of day, at least in terms of its pharmacokinetics.
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Antibacterianos/farmacocinética , Ritmo Circadiano , Levofloxacino/farmacocinética , Modelos Biológicos , Administración Oral , Adolescente , Adulto , Antibacterianos/sangre , Antibacterianos/orina , Simulación por Computador , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Electrocardiografía , Tasa de Filtración Glomerular , Humanos , Levofloxacino/sangre , Levofloxacino/orina , Masculino , Persona de Mediana Edad , Tirotropina/sangre , Adulto JovenRESUMEN
Misalignment of behavior and circadian rhythms due to night work can impair sleep and waking function. While both simulated and field-based studies suggest that circadian adaptation to a nocturnal schedule is slow, the rates of adaptation in real-world shift-work conditions are still largely unknown. The aim of this study was to evaluate the extent of adaptation of 24-h rhythms with 6-sulfatoxymelatonin (aMT6s) and cortisol in police officers working rotating shifts, with a special attention to night shifts. A total of 76 police officers (20 women; aged 32 ± 5.4 years, mean ± SD) from the province of Quebec, Canada, participated in a field study during their 28- or 35-day work cycle. Urine samples were collected for ~32 h before a series of day, evening, and night shifts to assess circadian phase. Before day, evening, and night shifts, 60%-89% of officers were adapted to a day schedule based on aMT6 rhythms, and 71%-78% were adapted based on cortisol rhythms. To further quantify the rate of circadian adaptation to night shifts, initial and final phases were determined in a subset of 37 officers with suitable rhythms for both hormones before and after 3-8 consecutive shifts (median = 7). Data were analyzed with circular and linear mixed-effects models. After night shifts, 30% and 24% of officers were adapted to a night-oriented schedule for aMT6s and cortisol, respectively. Significantly larger phase-delay shifts (aMT6s: -7.3 ± 0.9 h; cortisol: -6.3 ± 0.8 h) were observed in police officers who adapted to night shifts than in non-adapted officers (aMT6s: 0.8 ± 0.9 h; cortisol: 0.2 ± 1.1 h). Consistent with prior research, our results from both urinary aMT6s and cortisol midpoints indicate that a large proportion of police officers remained in a state of circadian misalignment following a series of night shifts in dim-light working environments.
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Ritmo Circadiano , Melatonina , Humanos , Femenino , Hidrocortisona , Policia , Tolerancia al Trabajo Programado , SueñoRESUMEN
BACKGROUND: The circadian timing system coordinates daily cycles in physiological functions, including glucose metabolism and insulin sensitivity. Here, the aim was to characterise the 24-h variation in glucose levels in critically ill patients during continuous enteral nutrition after controlling for potential sources of bias. METHODS: Time-stamped clinical data from adult patients who stayed in the Intensive Care Unit (ICU) for at least 4 days and received enteral nutrition were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Linear mixed-effects and XGBoost modelling were used to determine the effect of time of day on blood glucose values. FINDINGS: In total, 207,647 glucose measurements collected during enteral nutrition were available from 6,929 ICU patients (3,948 males and 2,981 females). Using linear mixed-effects modelling, time of day had a significant effect on blood glucose levels (p < 0.001), with a peak of 9.6 [9.5-9.6; estimated marginal means, 95% CI] mmol/L at 10:00 in the morning and a trough of 8.6 [8.5-8.6] mmol/L at 02:00 at night. A similar impact of time of day on glucose levels was found with the XGBoost regression model. INTERPRETATION: These results revealed marked 24-h variation in glucose levels in ICU patients even during continuous enteral nutrition. This 24-h pattern persists after adjustment for potential sources of bias, suggesting it may be the result of endogenous biological rhythmicity. FUNDING: This work was supported by a VENI grant from the Netherlands Organisation for Health Research and Development (ZonMw), an institutional project grant, and by the Dutch Research Council (NWO).
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Glucemia , Nutrición Enteral , Unidades de Cuidados Intensivos , Humanos , Masculino , Femenino , Glucemia/metabolismo , Nutrición Enteral/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Enfermedad Crítica , Ritmo Circadiano , AdultoRESUMEN
A wealth of data is available from electronic health records (EHR) that are collected as part of routine clinical care in hospitals worldwide. These rich, longitudinal data offer an attractive object of study for the field of circadian medicine, which aims to translate knowledge of circadian rhythms to improve patient health. This narrative review aims to discuss opportunities for EHR in studies of circadian medicine, highlight the methodological challenges, and provide recommendations for using these data to advance the field. In the existing literature, we find that data collected in real-world clinical settings have the potential to shed light on key questions in circadian medicine, including how 24-hour rhythms in clinical features are associated with-or even predictive of-health outcomes, whether the effect of medication or other clinical activities depend on time of day, and how circadian rhythms in physiology may influence clinical reference ranges or sampling protocols. However, optimal use of EHR to advance circadian medicine requires careful consideration of the limitations and sources of bias that are inherent to these data sources. In particular, time of day influences almost every interaction between a patient and the healthcare system, creating operational 24-hour patterns in the data that have little or nothing to do with biology. Addressing these challenges could help to expand the evidence base for the use of EHR in the field of circadian medicine.
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BACKGROUND: There are increased indications that physical activity timing, irrespective of intensity, impacts insomnia and circadian clock function. Here, we describe the rationale and design of a randomized cross-over study, called ON TIME, to examine the effects of (changing) physical activity timing on insomnia severity and on multiple exploratory outcomes that are linked to circadian clock function. METHODS: We will conduct a randomized cross-over trial in 40 healthy older adults (aged 65 to 75 years) with subclinical or clinical insomnia (Insomnia Severity Index (ISI) scores of ≥ 10) from the Dutch municipality of Leiden and surroundings. Participants will undergo 3 intervention periods (14 days each) consecutively: one sedentary period and two periods of increased physical activity (one period with morning activity and one period with evening activity). The intervention periods are separated by a wash-out period of 1 week. In both active intervention arms, participants will follow coached or uncoached outdoor physical exercise sessions comprising endurance, strength, and flexibility exercises for 14 days. The primary outcome is change in insomnia severity as measured by the ISI. Additional exploratory outcomes include multiple components of objective sleep quality measured with tri-axial accelerometry and subjective sleep quality assessed by questionnaires as well as dim light melatonin onset and 24-h rhythms in heart rate, heart rate variability, breathing rate, oxygen saturation, mood, and objective emotional arousal and stress. Additionally, we will collect diary data on eating patterns (timing and composition). Finally, fasting blood samples will be collected at baseline and after each intervention period for measurements of biomarkers of metabolic and physiological functioning and expression of genes involved in regulation of the biological clock. DISCUSSION: We anticipate that this study will make a significant contribution to the limited knowledge on the effect of physical activity timing. Optimizing physical activity timing has the potential to augment the health benefits of increased physical exercise in the aging population. TRIAL REGISTRATION: Trial was approved by the Medical Ethics Committee Leiden, The Hague, Delft, The Netherlands (June, 2023). The trial was registered in the CCMO-register https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm under study ID NL82335.058.22 and named ("Ouderen op tijd in beweging" or in English "Older adults exercising on time"). At time of manuscript submission, the trial was additionally registered at ClinicalTrials.gov under study ID: NL82335.058.22 and is awaiting approval.
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Estudios Cruzados , Ejercicio Físico , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Anciano , Factores de Tiempo , Masculino , Femenino , Índice de Severidad de la Enfermedad , Países Bajos , Ritmo Circadiano , Calidad del Sueño , Melatonina/sangre , Resultado del Tratamiento , Relojes Circadianos , Terapia por Ejercicio/métodos , Factores de EdadRESUMEN
AIM OF THE STUDY: The primary purpose was to examine sleep difficulties and delirium in the Intensive and Intermediate Care Unit. Secondarily, factors impacting night-time sleep duration and quality, mortality, and the impact of benzodiazepine use on sleep outcomes were investigated. MATERIALS AND METHODS: This retrospective study encompassed data from 323 intensive and intermediate care unit admissions collected in the Netherlands, spanning from November 2018 to May 2020. Sleep quality was measured using the Richards-Campbell Sleep Questionnaire. Night-time sleep duration was nurse-reported. We investigated associations of these sleep outcomes with age, sex, length-of-stay, natural daylight, disease severity, mechanical ventilation, benzodiazepine use, and delirium using Generalized Estimating Equations models. Associations with one-year post-discharge mortality were analyzed using Cox regression. RESULTS: Night-time sleep duration was short (median 4.5 hours) and sleep quality poor (mean score 4.9/10). Benzodiazepine use was common (24 % of included nights) and was negatively associated with night-time sleep duration and quality (B = -0.558 and -0.533, p <.001). Delirium and overnight transfers were negatively associated with sleep quality (B = -0.716 and -1.831, p <.05). The day-to-night sleep ratio was higher in the three days before delirium onset than in non-delirious individuals (p <.05). Age, disease severity and female sex were associated with increased one-year mortality. Sleep quality was negatively, but not-significantly, associated with mortality (p =.070). CONCLUSIONS: Night-time sleep in the critical care environment has a short duration and poor quality. Benzodiazepine use was not associated with improved sleep. Sleep patterns change ahead of delirium onset. IMPLICATIONS FOR CLINICAL PRACTICE: Consistent sleep monitoring should be part of routine nursing practice, using a validated instrument like the Richards-Campbell Sleep Questionnaire. Given the lack of proven efficacy of benzodiazepines in promoting sleep in critical care settings, it is vital to develop more effective sleep treatments that include non-benzodiazepine medication and sleep hygiene strategies.
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Benzodiazepinas , Delirio , Humanos , Femenino , Benzodiazepinas/efectos adversos , Estudios Retrospectivos , Cuidados Posteriores , Unidades de Cuidados Intensivos , Delirio/tratamiento farmacológico , Alta del Paciente , SueñoRESUMEN
Shift workers face an increased risk of metabolic health problems, but the direct metabolic response to working nights is not fully understood. The aim of this study was to investigate the effect of night shifts on the 24-h urinary metabolome of shift workers. Eleven police officers working rotating shifts completed two 24-h laboratory visits that took place before and after they worked 7 consecutive nights. Sleep and meals were scheduled on a day schedule in the first visit and then on a night schedule (i.e., sleep and meals shifted by approximately 12 h) in the second visit. Targeted metabolomic analysis was performed on urine samples collected throughout these laboratory visits. Differential rhythmicity analysis was used to compare 24-h rhythms in urinary metabolites in both conditions. Our results show that on the day schedule, 24-h rhythms are present in the urinary levels of the majority of metabolites, but that this is significantly reduced on the night schedule, partly due to loss of organic acid rhythmicity. Furthermore, misalignment of 24-h metabolite rhythms with the shifted behavioral cycles in the night schedule was observed in more than half of the metabolites that were rhythmic in both conditions (all acylcarnitines). These results show that working nights alters the daily rhythms of the urinary metabolome in rotating shift workers, with the most notable impact observed for acylcarnitines and organic acids, 2 metabolite classes involved in mitochondrial function. Further research is warranted to study how these changes relate to the increased metabolic risks associated with shift work.
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Ritmo Circadiano , Policia , Humanos , Ritmo Circadiano/fisiología , Sueño/fisiología , Tolerancia al Trabajo Programado/fisiología , Metaboloma , Admisión y Programación de PersonalRESUMEN
BACKGROUND: There is no consensus on reporting light characteristics in studies investigating non-visual responses to light. This project aimed to develop a reporting checklist for laboratory-based investigations on the impact of light on non-visual physiology. METHODS: A four-step modified Delphi process (three questionnaire-based feedback rounds and one face-to-face group discussion) involving international experts was conducted to reach consensus on the items to be included in the checklist. Following the consensus process, the resulting checklist was tested in a pilot phase with independent experts. FINDINGS: An initial list of 61 items related to reporting light-based interventions was condensed to a final checklist containing 25 items, based upon consensus among experts (final n = 60). Nine items were deemed necessary to report regardless of research question or context. A description of each item is provided in the accompanying Explanation and Elaboration (E&E) document. The independent pilot testing phase led to minor textual clarifications in the checklist and E&E document. INTERPRETATION: The ENLIGHT Checklist is the first consensus-based checklist for documenting and reporting ocular light-based interventions for human studies. The implementation of the checklist will enhance the impact of light-based research by ensuring comprehensive documentation, enhancing reproducibility, and enabling data aggregation across studies. FUNDING: Network of European Institutes for Advanced Study (NETIAS) Constructive Advanced Thinking (CAT) programme; Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust, 204686/Z/16/Z); Netherlands Organisation for Health Research and Development VENI fellowship (2020-09150161910128); U.S. Department of Defense Grant (W81XWH-16-1-0223); National University of Singapore (NUHSRO/2022/038/Startup/08); and National Research Foundation Singapore (NRF2022-THE004-0002).
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Lista de Verificación , Proyectos de Investigación , Estados Unidos , Humanos , Reproducibilidad de los Resultados , ConsensoRESUMEN
Study Objectives: This exploratory study assessed the impact of sex and hormonal contraceptives (HC) use on the homeostatic and diurnal variation of alertness, fatigue, sleepiness, psychomotor performance, and sleep behavior in police officers working rotating shifts. Methods: A total of 56 men and 20 women (6 using, 11 not using, and 3 with unknown use of HC) participated in an observational study throughout a month-long work cycle. Participants wore an actigraph, filled out a sleep and work log, answered questionnaires (Samn-Perelli, KSS, Visual Analogue Scales), and completed 5-min Psychomotor Vigilance Tasks (PVT) according to an ecological momentary assessment approach. Linear mixed-effects models were used to analyze the effects of group (men, women, and HC use), time awake, and time of day on the dependent variables. Results: Self-reported parameters and performance significantly varied with time awake and time of day. Women were more fatigued and sleepier than men, when considering both time awake and time of day. Compared to men, women using HC were more fatigued, less alert, and sleepier. Women had less attention lapses than men after 7 and 17 h awake, although no main effect of HC was detected. Conclusions: Women tended to rate themselves as more fatigued than men, especially when using HC. Surprisingly, psychomotor performances of women were sometimes better than those of men. This exploratory study indicates that sex and HC are important factors to consider in occupational medicine.
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Objectives: To characterize bedside 24-h patterns in light exposure in the Neonatal Intensive Care Unit (NICU) and to explore the environmental and individual patient characteristics that influence these patterns in this clinical setting. Methods: We conducted a retrospective cohort study that included 79 very preterm infants who stayed in an incubator with a built-in light sensor. Bedside light exposure was measured continuously (one value per minute). Based on these data, various metrics (including relative amplitude, intradaily variability, and interdaily stability) were calculated to characterize the 24-h patterns of light exposure. Next, we determined the association between these metrics and various environmental and individual patient characteristics. Results: A 24-h light-dark cycle was apparent in the NICU with significant differences in light exposure between the three nurse shifts (p < 0.001), with the highest values in the morning and the lowest values at night. Light exposure was generally low, with illuminances rarely surpassing 75 lux, and highly variable between patients and across days within a single patient. Furthermore, the season of birth and phototherapy had a significant effect on 24-h light-dark cycles, whereas no effect of bed location and illness severity were observed. Conclusion: Even without an official lighting regime set, a 24-h light-dark cycle was observed in the NICU. Various rhythmicity metrics can be used to characterize 24-h light-dark cycles in a clinical setting and to study the relationship between light patterns and health outcomes.
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Aging is associated with changes in heart rate (HR), heart rate variability (HRV), and 24-h rhythms in HR. Longevity has been linked to lower resting HR, while a higher resting HR and a decreased HRV were linked to cardiovascular events and increased mortality risk. HR and HRV are often investigated during a short electrocardiogram (ECG) measurement at a hospital. In this study, we aim to investigate the relationship between HR parameters with familial longevity and chronological age derived from continuous ambulatory ECG measurements collected over a period of 24 to 90 hours. We included 73 middle-aged participants (mean (SD) age: 67.0 (6.16) years), comprising 37 offspring of long-lived families, 36 of their partners, and 35 young participants (22.8 (3.96) years). We found no association with familial longevity, but middle-aged participants had lower 24-h HR (average and maximum HR, not minimum HR), lower amplitudes, and earlier trough and peak times than young participants. Associations in HR with chronological age could be caused by the aging process or by differences in environmental factors. Interestingly, middle-aged participants had a less optimal HRV during long-term recordings in both the sleep and awake periods, which might indicate that their heart is less adaptable than that of young participants. This could be a first indication of deteriorated cardiovascular health in middle-aged individuals.
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Electrocardiografía Ambulatoria , Longevidad , Anciano , Envejecimiento/fisiología , Electrocardiografía , Frecuencia Cardíaca/fisiología , Humanos , Longevidad/fisiología , Persona de Mediana EdadRESUMEN
The circadian timing system optimizes health by temporally coordinating behavior and physiology. During mammalian gestation, fetal circadian rhythms are synchronized by the daily fluctuations in maternal body temperature, hormones and nutrients. Circadian disruption during pregnancy is associated with negative effects on developmental outcomes in the offspring, highlighting the importance of regular and robust 24-h rhythms over gestation. In the case of preterm birth (before 37 weeks of gestation), maternal cues no longer synchronize the neonate's circadian system, which may adversely affect the neonate. There is increasing evidence that introducing robust light-dark cycles in the Neonatal Intensive Care Unit has beneficial effects on clinical outcomes in preterm infants, such as weight gain and hospitalization time, compared to infants exposed to constant light or constant near-darkness. However, the biological basis for these effects and the relationship with the functional and anatomical development of the circadian system is not fully understood. In this review, we provide a concise overview of the effects of light-dark cycles on clinical outcomes of preterm neonates in the NICU and its alignment with the development of the circadian system.
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Shift work, an essential part of our 24/7 society, inevitably leads to displacement of the habitual sleep period and thereby to misalignment of the internal circadian timing system with the rest-activity cycle and the environment. How interindividual differences in circadian organization affect sleep duration and timing during rotating shift work is not fully understood. The objective of this study was to assess the effect of chronotype, shift type, and their interaction on actigraphy-based sleep behavior in 74 police officers (20 women and 54 men; age [mean ± SD]: 32.1 ± 5.4 years) involved in rotating shift work throughout a 28- to 35-day work cycle consisting of morning, evening, and night shifts. Using linear mixed modeling, we found that chronotype was associated with sleep duration depending on the shift type: increasing morningness was correlated with longer sleep duration during series of consecutive morning shifts, while increasing eveningness was correlated with longer sleep duration during series of evening shifts. During series of night shifts, increasing eveningness was associated with a longer duration of the main sleep episode, but this relationship was attenuated and no longer significant when naps were taken into account due to increased napping in morning chronotypes during series of night shifts. Providing a detailed within-subject characterization of sleep behavior across a complete work cycle consisting of morning, evening, and night shifts, this study advances the understanding of the relationship between chronotype and sleep in rotating shift workers and supports the implementation of work schedules that take into account chronobiological principles.
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Horario de Trabajo por Turnos , Adulto , Ritmo Circadiano , Femenino , Humanos , Masculino , Sueño , Encuestas y Cuestionarios , Tolerancia al Trabajo ProgramadoRESUMEN
Premature birth (before 37 weeks of gestation) has been linked to a variety of adverse neurological outcomes. Sleep problems are associated with decreased neurocognitive functioning, which is especially common in children born preterm. The exact relationship between prematurity and sleep at school age is unknown. A systematic review is performed with the aim to assess the relationship between prematurity and sleep at school age (5th to 18th year of life), in comparison to sleep of their peers born full-term. Of 347 possibly eligible studies, nine were included. The overall conclusion is that prematurity is associated with earlier bedtimes and a lower sleep quality, in particular more nocturnal awakenings and more non-rapid eye movement stage 2 sleep. Interpretations and limitations of the review are discussed. Moreover, suggestions for future research are brought forward, including the need for a systematic approach with consistent outcome measures in this field of research. A better understanding of the mechanisms that influence sleep in the vulnerable group of children born preterm could help optimize these children's behavioral and intellectual development.