Patterns in behavioural sleep variables and social jetlag in elderly people of Western Odisha.

In humans, sleep is an essential physiological process for life and survival. The main objective of the current study is to determine the behavioural sleep patterns and social jetlag in elderly adults. The second objective is to define the relationship among subjective sleep quality, mid-sleep timings, social jetlag, and sunlight exposure. We recruited 945 female and 1047 male participants aged ≥ 60 years from 65 rural villages in the Sambalpur district of Odisha, India. The Munich Chrono Type Questionnaire (MCTQ) is a self-reported questionnaire that measures a person's behavioral sleep variables, including social jetlag and chronotype, whereas the Pittsburgh Sleep Quality Index (PSQI) measures the subjective sleep quality of an individual. We employed MCTQ and PSQI to obtain behavioral sleep variables and subjective sleep quality in the recruited subjects. The behavioral sleep variables were compared using a paired t-test on both work and work-free days. In addition, the behavioral sleep variables as a function of gender were compared using an independent Student's t-test. In the current study, most of the elderly individuals reported both midpoint of sleep on workdays (MSW) and midpoint of sleep on work-free days (MSF) between 00:01-03:00. The averages of mid-sleep timings between workdays and work-free days were not statistically significant. Data on MSFsc (midpoint of sleep on work-free days sleep corrected) indicated that most elderly adults (99.6%) are morning type; they go to bed early and wake up early. The elderly participants from the rural population of Sambalpur district in western Odisha had the least social jetlag and exhibited good subjective sleep quality. It would be worthwhile to find out the determinants of these positive features apropos social jetlag and behavioural sleep patterns.

Adverse Effect of Circadian Rhythm Disorder on Reparative Angiogenesis in Hind Limb Ischemia.

Background Circadian rhythm disorders, often seen in modern lifestyles, are a major social health concern. The aim of this study was to examine whether circadian rhythm disorders would influence angiogenesis and blood perfusion recovery in a mouse model of hind limb ischemia. Methods and Results A jet-lag model was established in C57BL/6J mice using a light-controlled isolation box. Control mice were kept at a light/dark 12:12 (12-hour light and 12-hour dark) condition. Concentrations of plasma vascular endothelial growth factor and circulating endothelial progenitor cells in control mice formed a circadian rhythm, which was diminished in the jet-lag model (P<0.05). The jet-lag condition deteriorated tissue capillary formation (P<0.001) and tissue blood perfusion recovery (P<0.01) in hind limb ischemia, which was associated with downregulation of vascular endothelial growth factor expression in local ischemic tissue and in the plasma. Although the expression of clock genes (ie, Clock, Bmal1, and Cry) in local tissues was upregulated after ischemic injury, the expression levels of cryptochrome (Cry) 1 and Cry2 were inhibited by the jet-lag condition. Next, Cry1 and Cry2 double-knockout mice were examined for blood perfusion recoveries and a reparative angiogenesis. Cry1 and Cry2 double-knockout mice revealed suppressed capillary density (P<0.001) and suppressed tissue blood perfusion recovery (P<0.05) in the hind limb ischemia model. Moreover, knockdown of CRY1/2 in human umbilical vein endothelial cells was accompanied by increased expression of WEE1 and decreased expression of HOXC5. This was associated with decreased proliferative capacity, migration ability, and tube formation ability of human umbilical vein endothelial cells, respectively, leading to impairment of angiogenesis. Conclusions Our data suggest that circadian rhythm disorder deteriorates reparative ischemia-induced angiogenesis and that maintenance of circadian rhythm plays an important role in angiogenesis.

Optimization of light exposure and sleep schedule for circadian rhythm entrainment.

The circadian rhythm, called Process C, regulates a wide range of biological processes in humans including sleep, metabolism, body temperature, and hormone secretion. Light is the dominant synchronizer of the circadian rhythm-it has been used to regulate the circadian phase to cope with jet-lag, shift work, and sleep disorder. The homeostatic oscillation of the sleep drive is called Process S. Process C and Process S together determine the sleep-wake cycle in what is known as the two-process model. This paper addresses the regulation of both Process C and Process S by scheduling light exposure and sleep based on numerical simulations of circadian rhythm and sleep mathematical models. This is a significant step beyond the existing literature that only considers the entrainment of Process C. Regulation of the two-process model poses several unique features and challenges: 1. Process S is non-smooth, i.e., the homeostatic dynamics are different in the sleep and wake regimes; 2. Light only indirectly affects Process S through Process C; 3. Light does not affect Process C during sleep. We consider two scenarios: optimizing light intensity as the control input with spontaneous (i.e., unscheduled) sleep/wake times and jointly optimizing the light intensity and the sleep/wake times, which allows limited delayed sleep and early waking as part of the decision variables. We solve the time-optimal entrainment problem for the two-process model for both scenarios using an extension of the gradient descent algorithm to non-smooth systems. To illustrate the efficacy of our time-optimal entrainment strategies, we consider two common use cases: transmeridian travelers and shift workers. For transmeridian travelers, joint optimization of the two-process model avoids the unrealistic long wake duration when only Process C is considered. The entrainment time also decreases when both the light input and the sleep schedule are optimized compared to when only the light input is optimized. For shift workers, we show that the entrainment time is significantly shortened by optimizing the night shift working light.

Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice.

Artificial lighting, day-length changes, shift work, and transmeridian travel all lead to sleep-wake disturbances. The nychthemeral sleep-wake cycle (SWc) is known to be controlled by output from the central circadian clock in the suprachiasmatic nuclei (SCN), which is entrained to the light-dark cycle. Additionally, via intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (Opn4), short-term light-dark alternations exert direct and acute influences on sleep and waking. However, the extent to which longer exposures typically experienced across the 24-h day exert such an effect has never been clarified or quantified, as disentangling sustained direct light effects (SDLE) from circadian effects is difficult. Recording sleep in mice lacking a circadian pacemaker, either through transgenesis (Syt10cre/creBmal1fl/- ) or SCN lesioning and/or melanopsin-based phototransduction (Opn4-/- ), we uncovered, contrary to prevailing assumptions, that the contribution of SDLE is as important as circadian-driven input in determining SWc amplitude. Specifically, SDLE were primarily mediated (>80%) through melanopsin, of which half were then relayed through the SCN, revealing an ancillary purpose for this structure, independent of its clock function in organizing SWc. Based on these findings, we designed a model to estimate the effect of atypical light-dark cycles on SWc. This model predicted SWc amplitude in mice exposed to simulated transequatorial or transmeridian paradigms. Taken together, we demonstrate this SDLE is a crucial mechanism influencing behavior on par with the circadian system. In a broader context, these findings mandate considering SDLE, in addition to circadian drive, for coping with health consequences of atypical light exposure in our society.

From circadian clock mechanism to sleep disorders and jet lag: Insights from a computational approach.

We present ten insights that can be gained from computational models based on molecular mechanisms for the mammalian circadian clock. These insights range from the conditions in which circadian rhythms occur spontaneously to their entrainment by the light-dark (LD) cycle and to clock-related disorders of the sleep-wake cycle. Endogenous oscillations originate spontaneously from transcription-translation feedback loops involving clock proteins such as PER, CRY, CLOCK and BMAL1. Circadian oscillations occur in a parameter domain bounded by critical values. Outside this domain the circadian network ceases to oscillate and evolves to a stable steady state. This conclusion bears on the nature of arrhythmic behavior of the circadian clock, which may not necessarily be due to mutations in clock genes. Entrainment by the LD cycle occurs in a certain range of parameter values, with a phase that depends on the endogenous period of the circadian clock. A decrease in PER phosphorylation is accompanied by a decrease in endogenous period and a phase advance of the clock; this situation accounts for the familial, advanced sleep phase syndrome (FASPS). The mirror delayed sleep phase syndrome (DSPS) can be accounted for, similarly, by an increase in PER phosphorylation and a rise in autonomous period. Failure of entrainment by the LD cycle in the model corresponds to the non-24 h sleep-wake cycle syndrome, in which the phase of the circadian clock drifts in the course of time. Quasi-periodic oscillations that develop in these conditions sometimes correspond to long-period patterns in which the circadian clock is nearly entrained for long bouts of time before its phase rapidly drifts until a new regime of quasi-entrainment is re-established. In regard to jet lag, the computational approach accounts for the two modes of re-entrainment observed after an advance or delay which correspond, respectively, to an eastward or westward flight: the clock adjusts in a direction similar (orthodromic) or opposite (antidromic) to that of the shift in the LD cycle. Computational modeling predicts that in the vicinity of the switch between orthodromic and antidromic re-entrainment the circadian clock may take a very long time to resynchronize with the LD cycle. Repetitive perturbations of the circadian clock due, for example, to chronic jet lag -a situation somewhat reminiscent of shift work- may lead to quasi-periodic or chaotic oscillations. The latter irregular oscillations can sometimes be observed in normal LD cycles, raising the question of their possible relevance to fragmented sleep patterns observed in narcolepsy. The latter condition, however, appears to originate from disorders in the orexin neural circuit, which promotes wakefulness, rather than from an irregular operation of the circadian clock.

Delays are Self-enhancing: An Explanation of the East-West Asymmetry in Recovery from Jetlag.

There is evidence in mammals that recovering from jetlag after westward travel is faster than after eastward travel. To understand why, mathematical models have been used, along with theories of entrainment rooted in experimental evidence. The most complete understanding relies on detailed mathematical modeling, so it is helpful to develop an intuition about why there is an east-west asymmetry. One such intuition is that humans have long periods and therefore recover better when they can delay. Although this is part of the reason, it does not explain why short-period mice also recover from westward travel faster. Our goal is to provide a simple intuition consistent with detailed mathematical theories, but which does not require mathematical expertise to follow. Here, we present the intuition that westward travel is easier to recover from because of a simple principle: delays are self-enhancing.

Sleep timing, chronotype and social jetlag: Impact on cognitive abilities and psychiatric disorders.

Sleep timing is controlled by the subtle interplay between circadian and homeostatic oscillators which, according to their endogenous properties, allow beings to feel spontaneously that it is time to go to bed or wake up in synchrony with the earth's light/dark cycle. In humans, however, social time and nocturnal artificial light modify sleep timing. Our modern lifestyle and artificial nocturnal light delay our bedtime, make us wake up, and lead to a greater intraindividual variability in sleep timing. Depending on the constraints that social time places on us, our sleep timing may be in or out of phase with the internal circadian timing determined by the circadian clock. When a person's social time is out of phase with their circadian time, they may be considered to suffer from circadian disruption or 'social jetlag'. There are interindividual differences in sleep timing that are known as morningness-eveningness preferences or chronotype, e.g. late chronotypes go to bed later. Chronotype may be assessed in terms of differences in kinetic homeostatic sleep pressure, intrinsic circadian period (ICP) and/or phase angle entrainment. In addition, chronotype depends on genetic and age-related factors, e.g. it gets earlier as people grow older. The social time of late chronotype individuals during week days is not adapted to their circadian time, unlike on free days. This results in social jetlag and circadian disruption, which in turn induces a chronic sleep debt due to a late bedtime and an early wake time, which is compensated on free days but only partially. Sleep and circadian clock disruption generally alter cognitive performance (alertness, attention, memory, higher-order executive functions such as response inhibition and decision-making) but their impact remains to be clarified. When subjects adopt their preferred sleep timing, a "synchrony effect" often appears with chronotypes performing better during daytime at optimal than at suboptimal timing (late chronotypes perform better in the evening, early chronotypes in the morning). Evening types appear to be cognitively more vulnerable to suboptimal times than morning types, probably because they have to deal with social jetlag and the "wake effort" period after awakening. Circadian disruption, but not chronotype, may impact attentional/inhibitory performance (more impulsivity and inattention). Strong associations have been found between mood disorders or attention deficit hyperactivity disorder (ADHD) and chronotype, with these psychiatric disorders typically being overrepresented in evening types. The association between social jetlag and these psychiatric disorders is less obvious. Social jetlag can be corrected by reducing exposure to evening light, although eveningness may be considered as a lifelong factor predisposing to depression or inattention.

Accelerometry-assessed sleep duration and timing in late childhood and adolescence in Scottish schoolchildren: A feasibility study.

Children and adolescents commonly suffer from sleep and circadian rhythm disturbances, which may contribute to poorer mental health and wellbeing during this critical developmental phase. Many studies however rely on self-reported sleep measures. This study assessed whether accelerometry data collection was feasible within the school setting as a method for investigating the extent of sleep and circadian disruption, and associations with subjective wellbeing, in Scotland. Fourteen days of wrist-worn accelerometry data were collected from 69 pupils, aged 10-14 years. Objective measures of sleep timing, sleep duration and circadian rest-activity patterns were derived. Questionnaires assessed subjective sleep timing, depressive symptoms, and experiences of wearing the accelerometer. Pupils slept on average less than 8 hours per night, failing to meet standard age-specific recommendations. Sleep timing was later and duration longer on weekends compared to weekdays (B = 0.87, 95% confidence interval (CI) 0.70, 1.04; B = 0.49, 95% CI 0.29, 0.69), indicating social jetlag. Lower daytime activity was correlated with higher depressive symptoms (r = -0.84, p = 0.008). Compared to primary school pupils, secondary pupils had shorter sleep window duration and lower circadian relative amplitude. Over half of participants reported some discomfort/inconvenience wearing the accelerometer. These data highlight that inadequate sleep is prevalent in this sample of schoolchildren. Future, larger scale investigations will examine in more detail the associations between sleep, circadian function and physical activity with mental health and wellbeing.

COVID-19-mandated social restrictions unveil the impact of social time pressure on sleep and body clock.

In humans, sleep regulation is tightly linked to social times that assign local time to events, such as school, work, or meals. The impact of these social times, collectively-social time pressure, on sleep has been studied epidemiologically via quantification of the discrepancy between sleep times on workdays and those on work-free days. This discrepancy is known as the social jetlag (SJL). COVID-19-mandated social restrictions (SR) constituted a global intervention by affecting social times worldwide. We launched a Global Chrono Corona Survey (GCCS) that queried sleep-wake times before and during SR (preSR and inSR). 11,431 adults from 40 countries responded between April 4 and May 6, 2020. The final sample consisted of 7517 respondents (68.2% females), who had been 32.7 ± 9.1 (mean ± sd) days under SR. SR led to robust changes: mid-sleep time on workdays and free days was delayed by 50 and 22 min, respectively; sleep duration increased on workdays by 26 min but shortened by 9 min on free days; SJL decreased by ~ 30 min. On workdays inSR, sleep-wake times in most people approached those of their preSR free days. Changes in sleep duration and SJL correlated with inSR-use of alarm clocks and were larger in young adults. The data indicate a massive sleep deficit under pre-pandemic social time pressure, provide insights to the actual sleep need of different age-groups and suggest that tolerable SJL is about 20 min. Relaxed social time pressure promotes more sleep, smaller SJL and reduced use of alarm clocks.

Changes in the Biorhythms of Biochemical Parameters in Animals with Modeled Acute Desynchronosis.

This article describes models for the study of acute desynchronosis: jetlag syndrome and acute desynchronosis under physical stress for possible pharmacological correction of these disorders. The cosinor analysis allowed assessing significance of changes in biological rhythms in 2 biological models: the jetlag-type diurnal rhythm shift model and the model with changed light mode. The revealed changes in the rhythms of biochemical parameters in the blood serum of animals with acute desynchronosis indicate significant changes in the intensity of carbohydrate-lipid metabolism, which affected the processes of cell bioenergetics. These changes are most pronounced in the group of animals that were kept under conditions of constant darkness, which can serve as a marker of the initial stage of pathological desynchronosis. The jetlag-type model can be used to evaluate the effectiveness of the pharmacological correction of physiological desynchronosis. The model with modified light regimen can be used for evaluation of the effectiveness of pharmacological correction of pathological desynchronosis.

Up in the Air: Evidence of Dehydration Risk and Long-Haul Flight on Athletic Performance.

The microclimate of an airline cabin consists of dry, recirculated, and cool air, which is maintained at lower pressure than that found at sea level. Being exposed to this distinctive, encapsulated environment for prolonged durations, together with the short-term chair-rest immobilization that occurs during long-haul flights, can trigger distinct and detrimental reactions to the human body. There is evidence that long-haul flights promote fluid shifts to the lower extremity and induce changes in blood viscosity which may accelerate dehydration, possibly compromising an athlete's potential for success upon arrival at their destination. Surprisingly, and despite several recent systematic reviews investigating the effects of jet lag and transmeridian travel on human physiology, there has been no systematic effort to address to what extent hypohydration is a (health, performance) risk to travelers embarking on long journeys. This narrative review summarizes the rationale and evidence for why the combination of fluid balance and long-haul flight remains a critically overlooked issue for traveling persons, be it for health, leisure, business, or in a sporting context. Upon review, there are few studies which have been conducted on actual traveling athletes, and those that have provide no real evidence of how the incidence rate, magnitude, or duration of acute dehydration may affect the general health or performance of elite athletes.

Intervention for Reducing Sleep Disturbances After a 12-Time Zone Transition.

Hoshikawa, M, Uchida, S, and Dohi, M. Intervention for reducing sleep disturbances after a 12-time zone transition. J Strength Cond Res 34(7): 1803-1807, 2020-The purpose of this study was to examine the effect of an intervention consisting of bright light exposure, sleep schedule shifts, and ramelteon on sleep disturbances after a transition of 12 time zones. Two groups, which flew from Tokyo to Rio, participated in this study. The experimental group received the treatment, whereas the control group did not receive any treatment. The experimental group members were exposed to bright light at night and their sleep-wake schedules were gradually delayed for 4 days before their flight. They also took 8 mg of ramelteon once a day for 5 days from the day of their first flight. Both groups departed Tokyo at 14:05, transiting through Frankfurt and arriving in Rio at 05:05. In Rio, it was recommended that they go to bed earlier than usual if they experienced sleepiness. Nocturnal sleep variables measured by wristwatch actigraphy and subjective morning tiredness were compared between groups. Statistical analysis revealed shorter sleep onset latencies (SOLs) in the experimental group (p < 0.01). The SOLs in Rio were 7.7 ± 2.5 minutes for the experimental group and 16.3 ± 3.7 minutes for the control group (d = 0.89, effect size: large). Sleep efficiency for the first 3 nights in Rio was 88.5 ± 1.2% for the experimental group and 82.9 ± 3.0% for the control group (p < 0.01, d = 1.09, effect size: large). These results suggest that the intervention reduced sleep disturbances in Rio. Our intervention may increase the options for conditioning methods for athletic events requiring time zone transitions.

Chocolate for breakfast prevents circadian desynchrony in experimental models of jet-lag and shift-work.

Night-workers, transcontinental travelers and individuals that regularly shift their sleep timing, suffer from circadian desynchrony and are at risk to develop metabolic disease, cancer, and mood disorders, among others. Experimental and clinical studies provide evidence that food intake restricted to the normal activity phase is a potent synchronizer for the circadian system and can prevent the detrimental metabolic effects associated with circadian disruption. As an alternative, we hypothesized that a timed piece of chocolate scheduled to the onset of the activity phase may be sufficient stimulus to synchronize circadian rhythms under conditions of shift-work or jet-lag. In Wistar rats, a daily piece of chocolate coupled to the onset of the active phase (breakfast) accelerated re-entrainment in a jet-lag model by setting the activity of the suprachiasmatic nucleus (SCN) to the new cycle. Furthermore, in a rat model of shift-work, a piece of chocolate for breakfast prevented circadian desynchrony, by increasing the amplitude of the day-night c-Fos activation in the SCN. Contrasting, chocolate for dinner prevented re-entrainment in the jet-lag condition and favored circadian desynchrony in the shift-work models. Moreover, chocolate for breakfast resulted in low body weight gain while chocolate for dinner boosted up body weight. Present data evidence the relevance of the timing of a highly caloric and palatable meal for circadian synchrony and metabolic function.

How to manage travel fatigue and jet lag in athletes? A systematic review of interventions.

OBJECTIVES: We investigated the management of travel fatigue and jet lag in athlete populations by evaluating studies that have applied non-pharmacological interventions (exercise, sleep, light and nutrition), and pharmacological interventions (melatonin, sedatives, stimulants, melatonin analogues, glucocorticoids and antihistamines) following long-haul transmeridian travel-based, or laboratory-based circadian system phase-shifts. DESIGN: Systematic review Eligibility criteria Randomised controlled trials (RCTs), and non-RCTs including experimental studies and observational studies, exploring interventions to manage travel fatigue and jet lag involving actual travel-based or laboratory-based phase-shifts. Studies included participants who were athletes, except for interventions rendering no athlete studies, then the search was expanded to include studies on healthy populations. DATA SOURCES: Electronic searches in PubMed, MEDLINE, CINAHL, Google Scholar and SPORTDiscus from inception to March 2019. We assessed included articles for risk of bias, methodological quality, level of evidence and quality of evidence. RESULTS: Twenty-two articles were included: 8 non-RCTs and 14 RCTs. No relevant travel fatigue papers were found. For jet lag, only 12 athlete-specific studies were available (six non-RCTs, six RCTs). In total (athletes and healthy populations), 11 non-pharmacological studies (participants 600; intervention group 290; four non-RCTs, seven RCTs) and 11 pharmacological studies (participants 1202; intervention group 870; four non-RCTs, seven RCTs) were included. For non-pharmacological interventions, seven studies across interventions related to actual travel and four to simulated travel. For pharmacological interventions, eight studies were based on actual travel and three on simulated travel. CONCLUSIONS: We found no literature pertaining to the management of travel fatigue. Evidence for the successful management of jet lag in athletes was of low quality. More field-based studies specifically on athlete populations are required with a multifaceted approach, better design and implementation to draw valid conclusions. PROSPERO registration number The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42019126852).

The effect of jet lag on the human brain: A neuroimaging study.

Jet lag is commonly experienced when travelers cross multiple time zones, leaving the wake-sleep cycle and intrinsic biological "clocks" out of synchrony with the current environment. The effect of jet lag on intrinsic cortical function remains unclear. Twenty-two healthy individuals experiencing west-to-east jet lag flight were recruited. Brain structural and functional magnetic resonance studies, as well as psychological and neurohormonal tests, were carried out when participants returned from travel over six time zones and 50 days later when their jet lag symptoms had resolved. During jet lag, the functional brain network exhibited a small-world topology that was shifted toward regularity. Alterations during jet lag relative to recovery included decreased basal ganglia-thalamocortical network connections and increased functional connectivity between the medial temporal lobe subsystem and medial visual cortex. The lower melatonin and higher thyroid hormone levels during jet lag showed the same trend as brain activity in the right lingual gyrus. Although there was no significant difference between cortisol measurements during and after jet lag, cortisol levels were associated with temporal lobe activity in the jet lag condition. Brain and neuroendocrine changes during jet lag were related to jet lag symptoms. Further prospective studies are needed to explore the time course over which jet lag acts on the human brain.

Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice.

Modern society characterized by a 24/7 lifestyle leads to misalignment between environmental cycles and endogenous circadian rhythms. Persisting circadian misalignment leads to deleterious effects on health and healthspan. However, the underlying mechanism remains not fully understood. Here, we subjected adult, wild-type mice to distinct chronic jet-lag paradigms, which showed that long-term circadian misalignment induced significant early mortality. Non-biased RNA sequencing analysis using liver and kidney showed marked activation of gene regulatory pathways associated with the immune system and immune disease in both organs. In accordance, we observed enhanced steatohepatitis with infiltration of inflammatory cells. The investigation of senescence-associated immune cell subsets from the spleens and mesenteric lymph nodes revealed an increase in PD-1+CD44high CD4 T cells as well as CD95+GL7+ germinal center B cells, indicating that the long-term circadian misalignment exacerbates immune senescence and consequent chronic inflammation. Our results underscore immune homeostasis as a pivotal interventional target against clock-related disorders.

Amplitude Effects Allow Short Jet Lags and Large Seasonal Phase Shifts in Minimal Clock Models.

Mathematical models of varying complexity have helped shed light on different aspects of circadian clock function. In this work, we question whether minimal clock models (Goodwin models) are sufficient to reproduce essential phenotypes of the clock: a small phase response curve (PRC), fast jet lag, and seasonal phase shifts. Instead of building a single best model, we take an approach where we study the properties of a set of models satisfying certain constraints; here, a 1h-pulse PRC with a range of 3h and clock periods between 22h and 26h is designed. Surprisingly, almost all these randomly parameterized models showed a 4h change in phase of entrainment between long and short days and jet lag durations of three to seven days in advance and delay. Moreover, intrinsic clock period influenced jet lag duration and entrainment amplitude and phase. Fast jet lag was realized in this model by means of an interesting amplitude effect: the association between clock amplitude and clock period termed "twist." This twist allows amplitude changes to speed up and slow down clocks enabling faster shifts. These findings were robust to the addition of positive feedback to the model. In summary, the known design principles of rhythm generation - negative feedback, long delay, and switch-like inhibition (we review these in detail) - are sufficient to reproduce the essential clock phenotypes. Furthermore, amplitudes play a role in determining clock properties and must be always considered, although they are difficult to measure.

The erythrocyte membrane stability is associated with sleep time and social jetlag in shift workers.

The osmotic stability of the erythrocyte membrane (OSEM) has been associated with changes in lipid profile, blood glucose and blood pressure. Changes in these parameters are very frequent in shift workers, possibly because of the lack of synchronization of biological rhythms, which results in the social jetlag. However, the existence of association between OSEM and circadian misalignment has not been investigated in this population. Therefore, this study investigated whether shift work, sleep time and social jetlag (SJL) are associated with biochemical and hematological variables. A population consisting of 79 men working at night (n = 37) or during the day (n = 42), aged between 21 and 65 years and with a mean BMI of 27.56 ± 4.0 kg/m2, was investigated cross-sectionally in relation to sleep time, SJL, anthropometric (height, weight and waist circumference) and blood variables, with emphasis on the OSEM. SJL was calculated by the absolute difference between the midpoint of sleep on work and rest days. The Generalized Linear Model (GzLM) was used to investigate the existence of associations between SJL and average sleep time in relation to the analyzed variables. Workers without SJL presented lower baseline lysis values of erythrocytes in isotonic medium in relation to workers with SJL. In addition, workers who slept on average less than 6 hours had higher OSEM, and higher total and LDL-cholesterol in relation to those who slept more than 6 hours, regardless of the shift. It is possible that the association of sleep deprivation and SJL with erythrocyte membrane stability is mediated through changes in the lipid profile.