Endogenous Rhythm Research Articles

Rapid changes in overnight blood pressure after transitioning to early-morning shiftwork.

Risk for adverse cardiovascular events increases when blood pressure does not decrease at night ("non-dipping," <10% decrease from daytime blood pressure). Shiftwork alters relationships between behaviors and endogenous circadian rhythms (i.e., circadian disruption along with variable sleep timing), and chronic shiftwork increases cardiovascular disease risk. To determine whether transitioning into shiftwork changes the overnight blood pressure dipping pattern, we leveraged a natural experiment that occurs when newly-hired bus operators transition from a daytime training schedule into an early-morning shiftwork or daywork schedule. Twenty participants were studied in a 90-day protocol upon new employment and underwent cardio-metabolic health assessments, including ambulatory blood pressure monitoring, and weekly sleep-wake diaries. Measurements were repeated after ~30 and 90 days after transitioning to a day or an early-morning shiftwork schedule. Newly-hired shiftworkers displayed dramatic changes in overnight blood pressure, with 62% converting from a healthy dipping blood pressure to the nondipping pattern, resulting in 93% of shiftworkers displaying a nondipping phenotype at 90-days. In contrast, 50% of dayworkers had a nondipping profile at baseline and this decreased to 0% at 90-days, a significant difference from shiftworkers (p = .001). At 90-days, overnight blood pressure dipping was ~7% less in shiftworkers than dayworkers (-6.3% [95%CI -3.7 to -8.8%] vs -13.1% [-10.3 to -15.9%]: p < .01), with changes in dipping associated with changes in sleep timing variability (r2 = .28, p = .03). The observed changes in overnight blood pressure dipping in newly-hired early-morning shiftworkers, which were associated with sleep timing variability, may be an early warning sign of increased cardiovascular risk among shiftworkers.

Acclimation to tidal conditions alters the physiological responses of the green shore crab, Carcinus maenas, to subsequent emersion.

Animals inhabiting the intertidal zone are exposed to abrupt changes in environmental conditions associated with the rise and fall of the tide. For convenience, the majority of laboratory studies on intertidal organisms have acclimated individuals to permanently submerged conditions in seawater tanks. In this study, green shore crabs, Carcinus maenas, were acclimated to either a simulated tidal regime of continuous emersion-immersion ('tidal') or to permanently submerged conditions ('non-tidal') to assess their physiological responses to subsequent emersion. Tidal crabs exhibited an endogenous rhythm of oxygen consumption during continuous submersion with lower oxygen consumption during periods of anticipated emersion, which was not detected in non-tidal crabs. During emersion, tidal crabs were able to buffer apparent changes in acid-base balance and exhibited no change in venous pH, whereas non-tidal crabs developed an acidosis associated with a rise in lactate levels. These results indicate that tidal crabs were better able to sustain aerobic metabolism and had lower metabolic costs during emersion than non-tidal crabs. It is likely that the elevated levels of haemocyanin exhibited by tidal crabs allowed them to maintain oxygen transport and buffer pH changes during emersion. This suggests that acclimation of C. maenas to submerged conditions results in a loss of important physiological mechanisms that enable it to tolerate emersion. The results of this study show that caution must be taken when acclimating intertidal organisms to submerged conditions in the laboratory, as it may abolish important physiological responses and adaptations that are critical to their performance when exposed to air.

Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers.

Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8hours sleep at night, four meals during a 16hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n=16 males, mean age±SD=23.4±2.3years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near-identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n=25, 14 females, 36.3±8.9years) across four protocols; two with abrupt 8hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8hour advance (1.6hours/day over 5days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by -3.7hours and -4.2hours, respectively, compared to -6.6hours and -4.7hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1hours) but not the gradual (+2.1hours) protocol, compared to +3.1hours and +2.8hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.

No Evidence for Entrainment: Endogenous Gamma Oscillations and Rhythmic Flicker Responses Coexist in Visual Cortex.

Over the past decades, numerous studies have linked cortical gamma oscillations (∼30–100 Hz) to neurocomputational mechanisms. Their functional relevance, however, is still passionately debated. Here, we asked whether endogenous gamma oscillations in the human brain can be entrained by a rhythmic photic drive >50 Hz. Such a noninvasive modulation of endogenous brain rhythms would allow conclusions about their causal involvement in neurocognition. To this end, we systematically investigated oscillatory responses to a rapid sinusoidal flicker in the absence and presence of endogenous gamma oscillations using magnetoencephalography (MEG) in combination with a high-frequency projector. The photic drive produced a robust response over visual cortex to stimulation frequencies of up to 80 Hz. Strong, endogenous gamma oscillations were induced using moving grating stimuli as repeatedly done in previous research. When superimposing the flicker and the gratings, there was no evidence for phase or frequency entrainment of the endogenous gamma oscillations by the photic drive. Unexpectedly, we did not observe an amplification of the flicker response around participants' individual gamma frequencies (IGFs); rather, the magnitude of the response decreased monotonically with increasing frequency. Source reconstruction suggests that the flicker response and the gamma oscillations were produced by separate, coexistent generators in visual cortex. The presented findings challenge the notion that cortical gamma oscillations can be entrained by rhythmic visual stimulation. Instead, the mechanism generating endogenous gamma oscillations seems to be resilient to external perturbation.SIGNIFICANCE STATEMENT We aimed to investigate to what extent ongoing, high-frequency oscillations in the gamma-band (30–100 Hz) in the human brain can be entrained by a visual flicker. Gamma oscillations have long been suggested to coordinate neuronal firing and enable interregional communication. Our results demonstrate that rhythmic visual stimulation cannot hijack the dynamics of ongoing gamma oscillations; rather, the flicker response and the endogenous gamma oscillations coexist in different visual areas. Therefore, while a visual flicker evokes a strong neuronal response even at high frequencies in the gamma-band, it does not entrain endogenous gamma oscillations in visual cortex. This has important implications for interpreting studies investigating the causal and neuroprotective effects of rhythmic sensory stimulation in the gamma-band.

The impact of stress and stress hormones on endogenous clocks and circadian rhythms

In mammals, daily rhythms in physiology and behavior are under control of a circadian pacemaker situated in the suprachiasmatic nucleus (SCN). This master clock receives photic input from the retina and coordinates peripheral oscillators present in other tissues, maintaining all rhythms in the body synchronized to the environmental light–dark cycle. In line with its function as a master clock, the SCN appears to be well protected against unpredictable stressful stimuli. However, available data indicate that stress and stress hormones at certain times of day are capable of shifting peripheral oscillators in, e.g., liver, kidney and heart, which are normally under control of the SCN. Such shifts of peripheral oscillators may represent a temporary change in circadian organization that facilitates adaptation to repeated stress. Alternatively, these shifts of internal rhythms may represent an imbalance between precisely orchestrated physiological and behavioral processes that may have severe consequences for health and well-being.

Clocks, Rhythms, Sex, and Hearts: How Disrupted Circadian Rhythms, Time-of-Day, and Sex Influence Cardiovascular Health.

Cardiovascular diseases are the top cause of mortality in the United States, and ischemic heart disease accounts for 16% of all deaths around the world. Modifiable risk factors such as diet and exercise have often been primary targets in addressing these conditions. However, mounting evidence suggests that environmental factors that disrupt physiological rhythms might contribute to the development of these diseases, as well as contribute to increasing other risk factors that are typically associated with cardiovascular disease. Exposure to light at night, transmeridian travel, and social jetlag disrupt endogenous circadian rhythms, which, in turn, alter carefully orchestrated bodily functioning, and elevate the risk of disease and injury. Research into how disrupted circadian rhythms affect physiology and behavior has begun to reveal the intricacies of how seemingly innocuous environmental and social factors have dramatic consequences on mammalian physiology and behavior. Despite the new focus on the importance of circadian rhythms, and how disrupted circadian rhythms contribute to cardiovascular diseases, many questions in this field remain unanswered. Further, neither time-of-day nor sex as a biological variable have been consistently and thoroughly taken into account in previous studies of circadian rhythm disruption and cardiovascular disease. In this review, we will first discuss biological rhythms and the master temporal regulator that controls these rhythms, focusing on the cardiovascular system, its rhythms, and the pathology associated with its disruption, while emphasizing the importance of the time-of-day as a variable that directly affects outcomes in controlled studies, and how temporal data will inform clinical practice and influence personalized medicine. Finally, we will discuss evidence supporting the existence of sex differences in cardiovascular function and outcomes following an injury, and highlight the need for consistent inclusion of both sexes in studies that aim to understand cardiovascular function and improve cardiovascular health.

Study of Parameters of Biological Rhythms of Plankton Communities in Natural Conditions

The change in the intensity of bioluminescence fields in the coastal area of the western shelf of the Crimea in the dark time of day was discussed. It is noted, that the biomass of luminous organisms closely correlate with the biomass of plankton and other pelagic creatures, including commercial pelagic fish. The parameters of the basic biological rhythms of plankton communities are found using method of Fourier series. These rhythms leads to change of intensity of the bioluminescence field. It is shown, that the change of the intensity of bioluminescence field with a 14 hours period due to duration of photo- and dark- periods. Changes in the intensity of the bioluminescence fields with periods of 4.7 and 2.8 hours due to endogenous circadian rhythms of plankton community. An original method for evaluation of errors of periods found of biological rhythms was proposed. The correlation coefficient between measured and calculated values of the intensity of the bioluminescence fields was estimated, taking into account the influence of three main biological rhythms, was r = 0.906, that confirms the correctness of the assumptions made.

Predictive visuo-motor communication through neural oscillations

SummaryThe mechanisms coordinating action and perception over time are poorly understood. The sensory cortex needs to prepare for upcoming changes contingent on action, and this requires temporally precise communication that takes into account the variable delays between sensory and motor processing. Several theorists1,2 have proposed synchronization of the endogenous oscillatory activity observed in most regions of the brain3 as the basis for an efficient and flexible communication protocol between distal brain areas,2,4 a concept known as “communication through coherence.” Synchronization of endogenous oscillations5,6 occurs after a salient sensory stimulus, such as a flash or a sound,7, 8, 9, 10, 11 and after a voluntary action,12, 13, 14, 15, 16, 17, 18 and this directly impacts perception, causing performance to oscillate rhythmically over time. Here we introduce a novel fMRI paradigm to probe the neural sources of oscillations, based on the concept of perturbative signals, which overcomes the low temporal resolution of BOLD signals. The assumption is that a synchronized endogenous rhythm will modulate cortical excitability rhythmically, which should be reflected in the BOLD responses to brief stimuli presented at different phases of the oscillation cycle. We record rhythmic oscillations of V1 BOLD synchronized by a simple voluntary action, in phase with behaviorally measured oscillations in visual sensitivity in the theta range. The functional connectivity between V1 and M1 also oscillates at the same rhythm. By demonstrating oscillatory temporal coupling between primary motor and sensory cortices, our results strongly implicate communication through coherence to achieve precise coordination and to encode sensory-motor timing.

Spontaneous Production Rates in Music and Speech.

Individuals typically produce auditory sequences, such as speech or music, at a consistent spontaneous rate or tempo. We addressed whether spontaneous rates would show patterns of convergence across the domains of music and language production when the same participants spoke sentences and performed melodic phrases on a piano. Although timing plays a critical role in both domains, different communicative and motor constraints apply in each case and so it is not clear whether music and speech would display similar timing mechanisms. We report the results of two experiments in which adult participants produced sequences from memory at a comfortable spontaneous (uncued) rate. In Experiment 1, monolingual pianists in Buffalo, New York engaged in three production tasks: speaking sentences from memory, performing short melodies from memory, and tapping isochronously. In Experiment 2, English-French bilingual pianists in Montréal, Canada produced melodies on a piano as in Experiment 1, and spoke short rhythmically-structured phrases repeatedly. Both experiments led to the same pattern of results. Participants exhibited consistent spontaneous rates within each task. People who produced one spoken phrase rapidly were likely to produce another spoken phrase rapidly. This consistency across stimuli was also found for performance of different musical melodies. In general, spontaneous rates across speech and music tasks were not correlated, whereas rates of tapping and music were correlated. Speech rates (for syllables) were faster than music rates (for tones) and speech showed a smaller range of spontaneous rates across individuals than did music or tapping rates. Taken together, these results suggest that spontaneous rate reflects cumulative influences of endogenous rhythms (in consistent self-generated rates within domain), peripheral motor constraints (in finger movements across tapping and music), and communicative goals based on the cultural transmission of auditory information (slower rates for to-be-synchronized music than for speech).

Seasonality, niche management and vertical migration in landscapes of relief

Landscapes of vertical relief, such as mountains and continental slopes, intensify ecological and climatological variation within narrow spatial windows. Seasonal vertical migrants exploit this variation during their residence in, and movements between, vertically stratified seasonal ranges. Animals in terrestrial, marine and even human‐ecological systems undergo similar patterns of seasonal vertical movements. The diversity of arenas in which vertical migration evolved lends insight to the factors promoting seasonal use of landscapes of relief. Because animals must contend with both endogenous circannual rhythms and exogenous environmental seasonality, vertical migrants may be sensitive to inconsistent change across stratified seasonal ranges under climate change. To better understand how ongoing and future climatic and environmental changes are likely to impact vertical migrants, we examine vertical migration in the context of niche tracking and niche switching. Whereas niche trackers minimize variation in realized environmental conditions throughout their seasonal movements, niche switchers undergo seasonal transitions in realized niche space. These strategies mediate the relationship between migrants and their changing environment, and can be used to forecast impacts of future change and effectively conserve systems of vertical migration. Niche tracking may be hindered by inconsistent or unpredictable environmental change along a single niche axis across strata, while niche switching may be sensitive to incongruous spatiotemporal change across factors. We suggest that climate change will affect seasonal patterns in vertical environments discontinuously across time, space and strata, and that vertical migrants are likely to face additional anthropogenic threats that interact with environmental seasonality. Conservation of vertical migrants should prioritize the availability of, and facilitate movement between, stratified seasonal ranges.

The Role of Colony Temperature in the Entrainment of Circadian Rhythms of Honey Bee Foragers.

Honey bees utilize their circadian rhythms to accurately predict the time of day. This ability allows foragers to remember the specific timing of food availability and its location for several days. Previous studies have provided strong evidence toward light/dark cycles being the primary Zeitgeber for honey bees. Work in our laboratory described large individual variation in the endogenous period length of honey bee foragers from the same colony and differences in the endogenous rhythms under different constant temperatures. In this study, we further this work by examining the temperature inside the honey bee colony. By placing temperature and light data loggers at different locations inside the colony we measured temperature at various locations within the colony. We observed significant oscillations of the temperature inside the hive, that show seasonal patterns. We then simulated the observed temperature oscillations in the laboratory and found that using the temperature cycle as a Zeitgeber, foragers present large individual differences in the phase of locomotor rhythms for temperature. Moreover, foragers successfully synchronize their locomotor rhythms to these simulated temperature cycles. Advancing the cycle by six hours, resulting in changes in the phase of activity in some foragers in the assay. The results are shown in this study highlight the importance of temperature as a potential Zeitgeber in the field. Future studies will examine the possible functional and evolutionary role of the observed phase differences of circadian rhythms.

Human Body Rhythms in the Development of Non-Invasive Methods of Closed-Loop Adaptive Neurostimulation.

The creation and improvement of non-invasive closed-loop brain stimulation technologies represent an exciting and rapidly expanding field of neuroscience. To identify the appropriate way to close the feedback loop in adaptive neurostimulation procedures, it was previously proposed to use on-line automatic sensory stimulation with the parameters modulated by the patient’s own rhythmical processes, such as respiratory rate, heart rate, and electroencephalogram (EEG) rhythms. The current paper aims to analyze several recent studies demonstrating further development in this line of research. The advantages of using automatic closed-loop feedback from human endogenous rhythms in non-invasive adaptive neurostimulation procedures have been demonstrated for relaxation assistance, for the correction of stress-induced functional disturbances, for anxiety management, and for the cognitive rehabilitation of an individual. Several distinctive features of the approach are noted to delineate its further development.

Tick-Tock Consider the Clock: The Influence of Circadian and External Cycles on Time of Day Variation in the Human Metabolome-A Review.

The past decade has seen a large influx of work investigating time of day variation in different human biofluid and tissue metabolomes. The driver of this daily variation can be endogenous circadian rhythms driven by the central and/or peripheral clocks, or exogenous diurnal rhythms driven by behavioural and environmental cycles, which manifest as regular 24 h cycles of metabolite concentrations. This review, of all published studies to date, establishes the extent of daily variation with regard to the number and identity of ‘rhythmic’ metabolites observed in blood, saliva, urine, breath, and skeletal muscle. The probable sources driving such variation, in addition to what metabolite classes are most susceptible in adhering to or uncoupling from such cycles is described in addition to a compiled list of common rhythmic metabolites. The reviewed studies show that the metabolome undergoes significant time of day variation, primarily observed for amino acids and multiple lipid classes. Such 24 h rhythms, driven by various factors discussed herein, are an additional source of intra/inter-individual variation and are thus highly pertinent to all studies applying untargeted and targeted metabolomics platforms, particularly for the construction of biomarker panels. The potential implications are discussed alongside proposed minimum reporting criteria suggested to acknowledge time of day variation as a potential influence of results and to facilitate improved reproducibility.

Photoperiod integration in C3H rd1 mice.

In mammals, the suprachiasmatic nuclei (SCN) constitute the main circadian clock, receiving input from the retina which allows synchronization of endogenous biological rhythms with the daily light/dark cycle. Over the year, the SCN encodes photoperiodic variations through duration of melatonin secretion, with abundant nocturnal levels in winter and lower levels in summer. Thus, light information is critical to regulate seasonal reproduction in many species and is part of the central photoperiodic integration. Since intrinsically photosensitive retinal ganglion cells (ipRGCs) are vital for circadian photoentrainment and other nonvisual functions, we studied the contribution of ipRGCs in photoperiod integration in C3H retinal degeneration 1 (rd1) mice. We assessed locomotor activity and melatonin secretion in mice exposed to short or long photoperiods. Our results showed that rd1 mice are still responsive to photoperiod variations in term of locomotor activity, melatonin secretion, and regulation of the reproductive axis. In addition, retinas of animals exposed to short photoperiod exhibit higher melanopsin labeling intensity compared with the long photoperiod condition, suggesting seasonal-dependent changes within this photoreceptive system. These results show that ipRGCs in rd1 mice can still measure photoperiod and suggest a key role of melanopsin cells in photoperiod integration and the regulation of seasonal physiology.

BBX19 fine-tunes the circadian rhythm by interacting with PSEUDO-RESPONSE REGULATOR proteins to facilitate their repressive effect on morning-phased clock genes.

The core plant circadian oscillator is composed of multiple interlocked transcriptional–translational feedback loops, which synchronize endogenous diel physiological rhythms to the cyclic changes of environmental cues. PSEUDO-RESPONSE REGULATORS (PRRs) have been identified as negative components in the circadian clock, though their underlying molecular mechanisms remain largely unknown. Here, we found that a subfamily of zinc finger transcription factors, B-box (BBX)-containing proteins, have a critical role in fine-tuning circadian rhythm. We demonstrated that overexpressing Arabidopsis thaliana BBX19 and BBX18 significantly lengthened the circadian period, while the null mutation of BBX19 accelerated the circadian speed. Moreover, BBX19 and BBX18, which are expressed during the day, physically interacted with PRR9, PRR7, and PRR5 in the nucleus in precise temporal ordering from dawn to dusk, consistent with the respective protein accumulation pattern of PRRs. Our transcriptomic and genetic analysis indicated that BBX19 and PRR9, PRR7, and PRR5 cooperatively inhibited the expression of morning-phased clock genes. PRR proteins affected BBX19 recruitment to the CCA1, LHY, and RVE8 promoters. Collectively, our findings show that BBX19 interacts with PRRs to orchestrate circadian rhythms, and suggest the indispensable role of transcriptional regulators in fine-tuning the circadian clock.

013 Associations Between Rest-Activity Rhythms and Nocturnal Blood Pressure are Sex-Dependent in Apparently Healthy Emerging Adults

Abstract Introduction Misalignment between endogenous circadian rhythms and environmental signals – an emerging risk factor for cardiovascular disease (CVD) – can disrupt diurnal blood pressure (BP) rhythms, resulting in higher nocturnal BP and less-pronounced BP dipping (i.e., % decline in nighttime systolic BP [SBP] relative to daytime values). Daily patterns of rest and activity (‘rest-activity rhythms’ [RAR]) are a proxy for estimating circadian disruption in free-living settings and have been independently associated with elevated CVD risk. However, the relation between RAR and nocturnal BP is unclear. Thus, we aimed to quantify the associations between RAR and nocturnal BP characteristics in male and female emerging adults (18-25y). Methods Fifty healthy emerging adults (20±1y; 20M/30F) underwent 24-h ambulatory BP monitoring following 14 consecutive days of continuous wrist actigraphy. RAR variables of interdaily stability (IS; day-to-day consistency in RAR), intradaily variability (IV; within-day fragmentation of RAR), and relative amplitude (RA; difference between trough vs. peak activity) were computed. Bivariate correlations were used to quantify associations between RAR variables and nocturnal BP characteristics for all participants, and separately for males and females. Linear regression models of mean nocturnal SBP, nocturnal diastolic BP (DBP), and SBP dipping were also generated to test main and interactive effects of sex and RAR. Potential confounders (variables associated with outcomes at p&amp;lt;0.10) of daytime BP, race, body mass index, physical activity, sleep duration, alcohol, caffeine, and sodium intake were also included as indicated. Results Overall, IS and RA positively correlated with % SBP dipping (IS: r=0.33, p=0.02; RA: r=0.35, p=0.01). Among females only, correlations strengthened (IS: r=0.50, p&amp;lt;0.01; RA: r=0.52, p&amp;lt;0.01) and an inverse association between RA and mean nocturnal SBP emerged (r=-0.46, p=0.01). Conversely, among males, no significant associations were apparent. Multivariate regressions revealed a significant sex*RAR interaction, such that in females, every 1-standard deviation increase in IS and RA were associated with an average decrease in nocturnal SBP of 5.4 mmHg (95% CI: -10.0, -0.73) and 4.8 mmHg (95% CI: -9.2, -0.34), respectively. Conclusion Findings suggest that consistent and high-amplitude RAR associate with more favorable nocturnal BP characteristics, particularly in emerging female adults. Support (if any) Supported in part by NIH P20-GM113125.

Circadian Phase Prediction From Non-Intrusive and Ambulatory Physiological Data.

Chronotherapy aims to treat patients according to their endogenous biological rhythms and requires, therefore, knowing their circadian phase. Circadian phase is partially determined by genetics and, under natural conditions, is normally entrained by environmental signals (zeitgebers), predominantly by light. Physiological data such as melatonin concentration and core body temperature (CBT) have been used to estimate circadian phase. However, due to their expensive and intrusive obtention, other physiological variables that also present circadian rhythmicity, such as heart rate variability, skin temperature, activity, and body position, have recently been proposed in several studies to estimate circadian phase. This study aims to predict circadian phase using minimally intrusive ambulatory physiological data modeled with machine learning techniques. Two approaches were considered; first, time-series were used to train artificial neural networks (ANNs) that predict CBT and melatonin dynamics and, second, a novel approach that uses scalar variables to build regression models that predict the time of the minimum CBT and the dim light melatonin onset (DLMO). ANNs require less than 48 hours of minimally intrusive data collection to predict circadian phase with an accuracy of less than one hour. On the other hand, regression models that use only three variables (body mass index, activity, and heart rate) are simpler and show higher accuracy with less than one minute of error, although they require longer times of data collection. This is a promising approach that should be validated in further studies considering a broader population and a wider range of conditions, including circadian misalignment.

Social interaction masking contributes to changes in the activity of the suprachiasmatic nucleus and impacts on circadian rhythms

Light is the most powerful temporal cue that entrains physiology and behavior through modulation of the suprachiasmatic nucleus (SCN) of the hypothalamus. However, on a daily basis, individuals face a combination of light and several non-photic cues, such as social interaction. In order to investigate whether SCN activity and SCN-driven rhythms are altered by social interaction, adult male C57BLJ/6 mice were maintained in groups of 3–4 animals per cage or 1 animal per cage (socially isolated) under 12:12 h / light:dark (LD) cycles or constant darkness (DD). Analysis of the two anatomical subdivisions (ventral, v and dorsal, d) of the medial SCN revealed an effect of housing conditions on the d-SCN but not on the v-SCN on the number of c-Fos immunoreactive (ir) neurons. As such, 2 h after the light-phase onset d-SCN c-Fos-ir number was lower in single-housed mice under LD. Importantly, under DD there were no effect of housing conditions in the number of c-Fos-ir SCN neurons. Social isolation increased the amplitude and strength of SCN-driven rhythm of body temperature (Tc) entrained to LD and it advanced its onset, uncoupling with spontaneous locomotor activity (SLA) rhythm, without altering endogenous Tc and SLA rhythms expressed under DD. Associated with reduced Tc in the light phase, single-housed mice showed reduced body weight. However, these phenotypes were not accompanied by changes in the number of c-Fos-ir neurons in the preoptic area (POA), which are known to regulate energy metabolism and Tc. Altogether, these results imply that the social interaction masking effect on the d-SCN is added to that of light stimulus, in order to achieve full c-Fos expression in the SCN, which, in turn seems to be required to maintain daily-phase coherence between the photo-entrained rhythms of Tc and SLA. There might be an inter-relationship between masking (social interaction) and entrainment stimulus (light) that impacts the circadian parameters of the photo-entrained Tc rhythm. As such, in the absence of social interactions a more robust Tc rhythm is shown. This inter-relationship seems to occur in the dorsal subdivision of the SCN but not in the POA.

Preoperative oral melatonin can reduce preoperative anxiety and postoperative analgesia in a dose-dependent manner

BackgroundPreoperative anxiety has deleterious effects on patients’ outcome through its influence on intraoperative requirements of anesthetics and analgesics (Bayrak et al., J Coll Physicians Surg Pak 29:868–873, 2019), postoperative (PO) pain intensity, and analgesia requirement, and may even increase PO morbidity and mortality after certain types of surgery. Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland at night under control of an endogenous rhythm of secretion generated by the suprachiasmatic nuclei. The current study hypothesized that preoperative melatonin could reduce patients’ anxiety and reduce intraoperative (IO) and postoperative (PO) analgesic in a dose-dependent manner.ResultsPreoperative consultation was, to some extent, effective in reducing patients’ anxiety and apprehension. At 1 h after receiving premedication, Anxiety Specific to Surgery Questionnaire (ASSQ) scores were significantly lower in study groups in comparison to baseline scores and at 1 h scores of P group patients (patients who received 3 ml of plain distilled water), and this significant effect extended for 3-h PO. The reported ∆∆ASSQ between study groups was 25.9% between M2 (melatonin) and Z (midazolam) groups and 36.9% between groups M1 (received melatonin in a dose of 3 mg) and M2 (received melatonin in a dose of 6 mg). Preoperative anxiolytic therapy allowed reduction of PO pain scores and analgesia consumption with prolongation of duration till 1st request of rescue analgesia, and these effects were more pronounced with melatonin 6 mg in comparison to placebo, melatonin 3mg, or midazolam.ConclusionPreoperative melatonin is an appropriate policy for reduction of preoperative anxiety and provided reduction of PO anxiety, pain scores, and consumption of analgesia thus promoting early recovery and short PO hospital stay. Dose dependency was evident, and preoperative melatonin 6-mg dose provided satisfactory effect.

Clocking cancer: the circadian clock as a target in cancer therapy.

Disruption of the cellular pathway modulating endogenous 24-h rhythms, referred to as "the circadian clock", has been recently proven to be associated with cancer risk, development, and progression. This pathway operates through a complex network of transcription-translation feedback loops generated by a set of interplaying proteins. The expression of core circadian clock genes is frequently dysregulated in human tumors; however, the specific effects and underlying mechanisms seem to vary depending on the cancer types and are not fully understood. In addition, specific oncogenes may differentially induce the dysregulation of the circadian clock in tumors. Pharmacological modulation of clock components has been shown to result in specific lethality in certain types of cancer cells, and thus holds great promise as a novel anti-cancer therapeutic approach. Here we present an overview of the rationale and current evidence for targeting the clock in cancer treatment.