Journal articles on the topic 'Rest-activity circadian rhythms: daily activity level'
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1
Aubourg, Timothée, Jacques Demongeot, and Nicolas Vuillerme. "Gaining Insights Into the Estimation of the Circadian Rhythms of Social Activity in Older Adults From Their Telephone Call Activity With Statistical Learning: Observational Study." Journal of Medical Internet Research 23, no. 1 (January 8, 2021): e22339. http://dx.doi.org/10.2196/22339.
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Background Understanding the social mechanisms of the circadian rhythms of activity represents a major issue in better managing the mechanisms of age-related diseases occurring over time in the elderly population. The automated analysis of call detail records (CDRs) provided by modern phone technologies can help meet such an objective. At this stage, however, whether and how the circadian rhythms of telephone call activity can be automatically and properly modeled in the elderly population remains to be established. Objective Our goal for this study is to address whether and how the circadian rhythms of social activity observed through telephone calls could be automatically modeled in older adults. Methods We analyzed a 12-month data set of outgoing telephone CDRs of 26 adults older than 65 years of age. We designed a statistical learning modeling approach adapted for exploratory analysis. First, Gaussian mixture models (GMMs) were calculated to automatically model each participant’s circadian rhythm of telephone call activity. Second, k-means clustering was used for grouping participants into distinct groups depending on the characteristics of their personal GMMs. Results The results showed the existence of specific structures of telephone call activity in the daily social activity of older adults. At the individual level, GMMs allowed the identification of personal habits, such as morningness-eveningness for making calls. At the population level, k-means clustering allowed the structuring of these individual habits into specific morningness or eveningness clusters. Conclusions These findings support the potential of phone technologies and statistical learning approaches to automatically provide personalized and precise information on the social rhythms of telephone call activity of older individuals. Futures studies could integrate such digital insights with other sources of data to complete assessments of the circadian rhythms of activity in elderly populations.
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Aubourg, Timothée, Jacques Demongeot, and Nicolas Vuillerme. "Gaining Insights Into the Estimation of the Circadian Rhythms of Social Activity in Older Adults From Their Telephone Call Activity With Statistical Learning: Observational Study." Journal of Medical Internet Research 23, no. 1 (January 8, 2021): e22339. http://dx.doi.org/10.2196/22339.
Full textAbstract:
Background Understanding the social mechanisms of the circadian rhythms of activity represents a major issue in better managing the mechanisms of age-related diseases occurring over time in the elderly population. The automated analysis of call detail records (CDRs) provided by modern phone technologies can help meet such an objective. At this stage, however, whether and how the circadian rhythms of telephone call activity can be automatically and properly modeled in the elderly population remains to be established. Objective Our goal for this study is to address whether and how the circadian rhythms of social activity observed through telephone calls could be automatically modeled in older adults. Methods We analyzed a 12-month data set of outgoing telephone CDRs of 26 adults older than 65 years of age. We designed a statistical learning modeling approach adapted for exploratory analysis. First, Gaussian mixture models (GMMs) were calculated to automatically model each participant’s circadian rhythm of telephone call activity. Second, k-means clustering was used for grouping participants into distinct groups depending on the characteristics of their personal GMMs. Results The results showed the existence of specific structures of telephone call activity in the daily social activity of older adults. At the individual level, GMMs allowed the identification of personal habits, such as morningness-eveningness for making calls. At the population level, k-means clustering allowed the structuring of these individual habits into specific morningness or eveningness clusters. Conclusions These findings support the potential of phone technologies and statistical learning approaches to automatically provide personalized and precise information on the social rhythms of telephone call activity of older individuals. Futures studies could integrate such digital insights with other sources of data to complete assessments of the circadian rhythms of activity in elderly populations.
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Bebas, Piotr, Bronislaw Cymborowski, and Jadwiga M. Giebultowicz. "Circadian rhythm of acidification in insect vas deferens regulated by rhythmic expression of vacuolar H+-ATPase." Journal of Experimental Biology 205, no. 1 (January 1, 2002): 37–44. http://dx.doi.org/10.1242/jeb.205.1.37.
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SUMMARY Recent studies have demonstrated that the peripheral tissues of vertebrates and invertebrates contain circadian clocks; however, little is known about their functions and the rhythmic outputs that they generate. To understand clock-controlled rhythms at the cellular level, we investigated a circadian clock located in the reproductive system of a male moth (the cotton leaf worm Spodoptera littoralis) that is essential for the production of fertile spermatozoa. Previous work has demonstrated that spermatozoa are released from the testes in a daily rhythm and are periodically stored in the upper vas deferens (UVD). In this paper, we demonstrate a circadian rhythm in pH in the lumen of the UVD, with acidification occurring during accumulation of spermatozoa in the lumen. The daily rhythm in pH correlates with a rhythmic increase in the expression of a proton pump, the vacuolar H+-ATPase (V-ATPase), in the apical portion of the UVD epithelium. Rhythms in pH and V-ATPase persist in light/dark cycles and constant darkness, but are abolished in constant light, a condition that disrupts clock function and renders spermatozoa infertile. Treatment with colchicine impairs the migration of V-ATPase-positive vesicles to the apical cell membrane and abates the acidification of the UVD lumen. Bafilomycin, a selective inhibitor of V-ATPase activity, also prevents the decline in luminal pH. We conclude that the circadian clock generates a rhythm of luminal acidification by regulating the levels and subcellular distribution of V-ATPase in the UVD epithelium. Our data provide the first evidence for circadian control of V-ATPase, the fundamental enzyme that provides the driving force for numerous secondary transport processes. They also demonstrate how circadian rhythms displayed by individual cells contribute to the synchrony of physiological processes at the organ level.
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Alós, Josep, Martina Martorell-Barceló, and Andrea Campos-Candela. "Repeatability of circadian behavioural variation revealed in free-ranging marine fish." Royal Society Open Science 4, no. 2 (February 2017): 160791. http://dx.doi.org/10.1098/rsos.160791.
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Repeatable between-individual differences in the behavioural manifestation of underlying circadian rhythms determine chronotypes in humans and terrestrial animals. Here, we have repeatedly measured three circadian behaviours, awakening time, rest onset and rest duration, in the free-ranging pearly razorfish, Xyrithchys novacula , facilitated by acoustic tracking technology and hidden Markov models. In addition, daily travelled distance, a standard measure of daily activity as fish personality trait, was repeatedly assessed using a State-Space Model. We have decomposed the variance of these four behavioural traits using linear mixed models and estimated repeatability scores ( R ) while controlling for environmental co-variates: year of experimentation, spatial location of the activity, fish size and gender and their interactions. Between- and within-individual variance decomposition revealed significant R s in all traits suggesting high predictability of individual circadian behavioural variation and the existence of chronotypes. The decomposition of the correlations among chronotypes and the personality trait studied here into between- and within-individual correlations did not reveal any significant correlation at between-individual level. We therefore propose circadian behavioural variation as an independent axis of the fish personality, and the study of chronotypes and their consequences as a novel dimension in understanding within-species fish behavioural diversity.
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Li, Jia-Da, Katherine J. Burton, Chengkang Zhang, Shuang-Bao Hu, and Qun-Yong Zhou. "Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 296, no. 3 (March 2009): R824—R830. http://dx.doi.org/10.1152/ajpregu.90463.2008.
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The suprachiasmatic nuclei (SCN) serve as the principal circadian pacemakers that coordinate daily cycles of behavior and physiology for mammals. A network of transcriptional and translational feedback loops underlies the operating molecular mechanism for circadian oscillation within the SCN neurons. It remains unclear how timing information is transmitted from SCN neurons to eventually evoke circadian rhythms. Intercellular communication between the SCN and its target neurons is critical for the generation of coherent circadian rhythms. At the molecular level, neuropeptides encoded by clock-controlled genes have been indicated as important output mediators. Arginine vasopressin (AVP) is the product of one such clock-controlled gene. Previous studies have demonstrated a circadian rhythm of AVP levels in the cerebrospinal fluid and the SCN. The physiological effects of AVP are mediated by three types of AVP receptors, designated as V1a, V1b, and V2. In this study, we report that V1a mRNA levels displayed a circadian rhythm in the SCN, peaking during night hours. The circadian rhythmicity of locomotor activities was significantly reduced in V1a-deficient ( V1a−/−) mice (50–75% reduction in the power of fast Fourier transformation). However, the light masking and light-induced phase shift effects are intact in V1a−/− mice. Whereas the expression of clock core genes was unaltered, the circadian amplitude of prokineticin 2 ( PK2) mRNA oscillation was attenuated in the SCN of V1a−/− mice (∼50% reduction in the peak levels). In vitro experiments demonstrated that AVP, acting through V1a receptor, was able to enhance the transcriptional activity of the PK2 promoter. These studies thus indicate that AVP-V1a signaling plays an important role in the generation of overt circadian rhythms.
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Ragozin, Oleg N., Irina A. Pogonysheva, Elena Yu Shalamova, Denis A. Pogonyshev, Elina R. Ragozina, and Victoria V. Postnikova. "Variability of Helioclimate Factors and Applicability to the Emergency Service Population of the Northern Region." Bulletin of Nizhnevartovsk State University, no. 4 (December 7, 2022): 89–97. http://dx.doi.org/10.36906/2311-4444/22-4/09.
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The purpose of this study was to study the influence of the variability of weather and heliophysical factors on the appeal to the Ambulance service for different groups of nosologies in the population of the Russian North. Information about calls to the emergency medical service of Khanty-Mansiysk was obtained from the database of calls for the period from 2001 to 2021 by disease classes (ICD-10). To assess the dynamics of weather factors, data from the All-Russian Research Institute of Hydrometeorological Information and materials from the weather station of Khanty-Mansiysk were used. The dynamics of air temperature; barometric pressure; relative humidity; baric trend; maximum wind speed; weight oxygen content in the air are analyzed. Data on the relative daily number of sunspots are obtained from the materials of the Royal Observatory of Belgium. The average daily values of the level of planetary geomagnetic activity, expressed by the Ap index, are copied from the website of the National Center for Geophysical Data of the USA (Boulder). Mathematical processing was carried out using wavelet analysis. The graph of temperature fluctuations for the period from 2001 to 2021 shows a significant circadian cyclicity and a semi-annual rhythm with a high level of trend. Significant rhythms of barometric pressure with a period of 5 years, 1 year and rhythms close to semi-annual, seasonal and near-monthly are observed. Humidity changes significantly in the circadian and intra-annual rhythms. The baric tendency has significant rhythms: 3 years, 1 year, 6, 3, 2 months. Changes in the maximum wind speed do not have a circadian rhythm, but intra-annual monthly variations are observed. The value of the weight oxygen content has circadian; two-year, five-year; two- and near-monthly rhythms. The relative number of sunspots (W) for the period from 2001 to 2021 is characterized by a five-, two-year and circadian rhythm. When considering the variations of the number W for the period from 1818 to 2017, in addition to the classic eleven-year, annual and near-monthly, rhythms with a period of 42.5 years, 18.1 years and 2.1 years are found. The index of planetary geomagnetic activity (Ar) has a rhythm with a period of 4 years, two-year and near-annual. The significance of all rhythms is p=0.001. When analyzing fluctuations in geomagnetic activity from 1932 to 2016, long-term rhythms are added: 35.00 years; 16.06 years; 10.88 years; semi-annual and three-month rhythms. Despite numerous hypotheses of the search for cosmobiological harmony in the form of evolutionary synchronisms, rhythmic cascades, golden section, the problem of the interaction of exogenous natural rhythms and endogenous rhythms of the human body remains largely unresolved. Comparison of the results of various studies is difficult due to methodological and mathematical approaches. With observation periods of 100-200 years or more, a long-period component is monitored, and in clinical studies (from a day to a week), short-period components are detected. Changing the background in the form of helioclimatic and social variations also does not add accuracy. The use of various methods of time series analysis involves obtaining information of different resolution levels (Fourier transform, SWANN, wavelet analysis). Nevertheless, the results obtained track the classical rhythms of solar and geomagnetic activity with periods of about eleven years, a year and a month. There is also a 35-year-old rhythm, a 42.5-year-old rhythm close to the 44.16-year rhythm identified by Bezrukova A.Ya., at 18.1 years (long-period components of the lunar tide) and other intra-annual rhythms with periods from two weeks to 9 months. The effect of helioclimatic factors on human health indicates the absence of constant coherence (in our case, the consistency of these processes over time, manifested when they are combined), due to the presence of a large number of mega- and mesorhythms, which is manifested by amplitude and phase desynchronization of heliogeophysical indicators and health status.
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Huffeldt, Nicholas Per, and Flemming R. Merkel. "Sex-specific, inverted rhythms of breeding-site attendance in an Arctic seabird." Biology Letters 12, no. 9 (September 2016): 20160289. http://dx.doi.org/10.1098/rsbl.2016.0289.
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In contrast to daily rhythms that are common in the presence of the geophysical light–dark cycle, organisms at polar latitudes exhibit many diel activity patterns during natural periods of continuous solar light or darkness (polar day and night, respectively), from 24 h rhythms to arrhythmicity. In Arctic Greenland (73.7° N, 56.6° W) during polar day, we observed breeding-site attendance rhythms of thick-billed murres ( Uria lomvia ; n = 21 pairs), a charadriiform seabird, which provide biparental care at the colony. We found that U. lomvia egg-incubation and chick-brooding attendance is rhythmic and synchronized to the geophysical day (mean period length [rhythm duration] ± 95% confidence interval = 24.13 ± 0.52 h). Individual pair members had temporally segregated, sex-specific colony-attendance rhythms that were opposite (inverted) to each other, and these sex-specific rhythms were prominent at the population level. Our results provide a basis for investigating circadian systems at polar latitudes and sex-specific parental-care strategies.
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Hsieh, Wan-Hsin, Carolina Escobar, Tatiana Yugay, Men-Tzung Lo, Benjamin Pittman-Polletta, Roberto Salgado-Delgado, Frank A. J. L. Scheer, Steven A. Shea, Ruud M. Buijs, and Kun Hu. "Simulated shift work in rats perturbs multiscale regulation of locomotor activity." Journal of The Royal Society Interface 11, no. 96 (July 6, 2014): 20140318. http://dx.doi.org/10.1098/rsif.2014.0318.
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Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation.
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Cenek, Lisa, Liubou Klindziuk, Cindy Lopez, Eleanor McCartney, Blanca Martin Burgos, Selma Tir, Mary E. Harrington, and Tanya L. Leise. "CIRCADA: Shiny Apps for Exploration of Experimental and Synthetic Circadian Time Series with an Educational Emphasis." Journal of Biological Rhythms 35, no. 2 (January 28, 2020): 214–22. http://dx.doi.org/10.1177/0748730419900866.
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Circadian rhythms are daily oscillations in physiology and behavior that can be assessed by recording body temperature, locomotor activity, or bioluminescent reporters, among other measures. These different types of data can vary greatly in waveform, noise characteristics, typical sampling rate, and length of recording. We developed 2 Shiny apps for exploration of these data, enabling visualization and analysis of circadian parameters such as period and phase. Methods include the discrete wavelet transform, sine fitting, the Lomb-Scargle periodogram, autocorrelation, and maximum entropy spectral analysis, giving a sense of how well each method works on each type of data. The apps also provide educational overviews and guidance for these methods, supporting the training of those new to this type of analysis. CIRCADA-E (Circadian App for Data Analysis–Experimental Time Series) allows users to explore a large curated experimental data set with mouse body temperature, locomotor activity, and PER2::LUC rhythms recorded from multiple tissues. CIRCADA-S (Circadian App for Data Analysis–Synthetic Time Series) generates and analyzes time series with user-specified parameters, thereby demonstrating how the accuracy of period and phase estimation depends on the type and level of noise, sampling rate, length of recording, and method. We demonstrate the potential uses of the apps through 2 in silico case studies.
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Caster, Stephen Z., Kathrina Castillo, Matthew S. Sachs, and Deborah Bell-Pedersen. "Circadian clock regulation of mRNA translation through eukaryotic elongation factor eEF-2." Proceedings of the National Academy of Sciences 113, no. 34 (August 9, 2016): 9605–10. http://dx.doi.org/10.1073/pnas.1525268113.
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The circadian clock has a profound effect on gene regulation, controlling rhythmic transcript accumulation for up to half of expressed genes in eukaryotes. Evidence also exists for clock control of mRNA translation, but the extent and mechanisms for this regulation are not known. In Neurospora crassa, the circadian clock generates daily rhythms in the activation of conserved mitogen-activated protein kinase (MAPK) pathways when cells are grown in constant conditions, including rhythmic activation of the well-characterized p38 osmosensing (OS) MAPK pathway. Rhythmic phosphorylation of the MAPK OS-2 (P-OS-2) leads to temporal control of downstream targets of OS-2. We show that osmotic stress in N. crassa induced the phosphorylation of a eukaryotic elongation factor-2 (eEF-2) kinase, radiation sensitivity complementing kinase-2 (RCK-2), and that RCK-2 is necessary for high-level phosphorylation of eEF-2, a key regulator of translation elongation. The levels of phosphorylated RCK-2 and phosphorylated eEF-2 cycle in abundance in wild-type cells but not in cells deleted for OS-2 or the core clock component FREQUENCY (FRQ). Translation extracts from cells grown in constant conditions show decreased translational activity in the late subjective morning, coincident with the peak in eEF-2 phosphorylation, and rhythmic translation of glutathione S-transferase (GST-3) from constitutive mRNA levels in vivo is dependent on circadian regulation of eEF-2 activity. In contrast, rhythms in phosphorylated eEF-2 levels are not necessary for rhythms in accumulation of the clock protein FRQ, indicating that clock control of eEF-2 activity promotes rhythmic translation of specific mRNAs.
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Karavanskyi, Yu V., I. L. Ryzhko, and V. V. Zamorov. "CIRCADE RHYTHMS OF PINCHUK'S GOBY PONTICOLA CEPHALARGOIDES (PINCHUK, 1976) IN LABORATORY CONDITIONS." Odesa National University Herald. Biology 26, no. 2(49) (December 29, 2021): 37–47. http://dx.doi.org/10.18524/2077-1746.2021.2(49).246881.
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Introduction. Circadian rhythms help the body to anticipate changes in environmental conditions and adapt to the daily fluctuations of external factors. The presence of such mechanisms, which provide early preparation of the organism, gives an advantage in the struggle for survival. The dynamics of light is one of the main factors, which determines the level of growth, development, nutrition, metabolism, affects hormonal activity. Aim. The aim of the study was to study the circadian rhythms of motor activity of Pinchuk's goby Ponticola cephalargoides (Pinchuk, 1976) in the laboratory. Methods. To study the activity of the fish individuals of the Pinchuk's goby caught in the Gulf of Odesa on a fishing rod were selected. The experiments were performed in an aquarium with two lighting options – under natural light and in the complete round-the-clock absence of lighting. Measurements of the fish activity were recorded at 1 hour intervals for 5 days. Results. The study revealed that the activity in constant darkness is generally lower than in the natural light. In both cases, the maximum value of the motor activity occurs in the first half of the day. Under the natural light, the activity of the Pinchuk's goby reaches the maximum value from 06:00 to 07:00, in constant darkness the activity reaches the maximum from 07:00 to 08:00. The difference in the activity of the fish between the two lighting modes is most noticeable from 16:00 to 22:00. Conclusion. It is established that the activity of Pinchuk's goby is cyclical both under the natural light conditions and in the absence of light. From 00:00 to 16:00 Pinchuk's goby has an endogenous circadian rhythm, from 16:00 to 22:30 the rhythm is exogenous.
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Herzog, Erik D., and Rachel M. Huckfeldt. "Circadian Entrainment to Temperature, But Not Light, in the Isolated Suprachiasmatic Nucleus." Journal of Neurophysiology 90, no. 2 (August 2003): 763–70. http://dx.doi.org/10.1152/jn.00129.2003.
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The suprachiasmatic nucleus (SCN) is the master pacemaker that drives circadian rhythms in mammalian physiology and behavior. The abilities to synchronize to daily cycles in the environment and to keep accurate time over a range of physiologic temperatures are two fundamental properties of circadian pacemakers. Recordings from a bioluminescent reporter ( Per1-luc) of Period1 gene activity in rats showed that the cultured SCN entrained to daily, 1.5°C cycles of temperature, but did not synchronize to daily light cycles. Temperature entrainment developed by 1 day after birth. Light cycles failed to affect the isolated SCN of rats aged 2 to 339 days. Entrainment to a 3-h shift in the warm-cool cycle was possible in <3 days with 3°C cycles. Importantly, Per1-luc expression in vitro was similar to that seen in vivo where peak expression occurs approximately 1 h prior to the daily increase in temperature. In addition, the firing rate of individual mouse SCN neurons continued to express near 24-h rhythms from 24–37°C. At lower temperatures, the percentage of rhythmic cells was reduced, but periodicity was temperature compensated. The results indicate that normal rhythms in brain temperature may serve to stabilize rhythmicity of the circadian system in vivo and that temperature compensation of this period is determined at the level of individual SCN cells.
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Siehler, Oliver, Shuo Wang, and Guy Bloch. "Social synchronization of circadian rhythms with a focus on honeybees." Philosophical Transactions of the Royal Society B: Biological Sciences 376, no. 1835 (August 23, 2021): 20200342. http://dx.doi.org/10.1098/rstb.2020.0342.
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Many animals benefit from synchronizing their daily activities with conspecifics. In this hybrid paper, we first review recent literature supporting and extending earlier evidence for a lack of clear relationship between the level of sociality and social entrainment of circadian rhythms. Social entrainment is specifically potent in social animals that live in constant environments in which some or all individuals do not experience the ambient day-night cycles. We next focus on highly social honeybees in which there is good evidence that social cues entrain the circadian clocks of nest bees and can override the influence of conflicting light-dark cycles. The current understanding of social synchronization in honeybees is consistent with self-organization models in which surrogates of forager activity, such as substrate-borne vibrations and colony volatiles, entrain the circadian clocks of bees dwelling in the dark cavity of the nest. Finally, we present original findings showing that social synchronization is effective even in an array of individually caged callow bees placed on the same substrate and is improved for bees in connected cages. These findings reveal remarkable sensitivity to social time-giving cues and show that bees with attenuated rhythms (weak oscillators) can nevertheless be socially synchronized to a common phase of activity. This article is part of the theme issue ‘Synchrony and rhythm interaction: from the brain to behavioural ecology’.
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Perebetyuk, L. S., L. V. Moroz, S. V. Shevchuk, Y. S. Segeda, and O. E. Shtatko. "Daily interleukin-1β variability in women with rheumatoid arthritis associated with fibromyalgia." Reports of Vinnytsia National Medical University 23, no. 4 (December 30, 2019): 616–20. http://dx.doi.org/10.31393/reports-vnmedical-2019-23(4)-10.
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Annotation. Disorders of circadian rhythms are considered to be one of the factors associated with the development of joint diseases. In patients with rheumatoid arthritis (RA) disorders of the neurohumoral regulation of circadian rhythms is a factor in the increased production of inflammatory cytokines in the joint tissues. In 30 % of RA patients, concomitant fibromyalgia (FM) is found, in which disorders of circadian regulation can deepen. Circadian features of the production of pain mediators and inflammation in RA patients with comorbid fibromyalgia (FM) have not been established. The aim of this study was to investigate the daily variability of serum interleukin-1β levels in RA patients depending on the comorbidity of FM. Materials and methods: 49 patients with rheumatoid arthritis (RA) (100 % female) aged 46.8 (39–53) years, with moderate and high disease activity (DAS28>3.2), of which 21 (42.9 %) patients with concomitant fibromyalgia (FM). Diagnosis of RA was established by ACR/EULAR criteria (2010), FM was diagnosed by mACR 2010. Blood sampling was performed twice daily (at 08-00 and at 20-00), the level of IL-1β in the blood was determined by enzyme immunoassay. The studies were conducted according to bioethical standards. Statistical processing of the results was performed by SPSS Statistics 22.0. Results: In RA patients circadian fluctuations of IL-1β level in blood were registered. IL-1β levels (08-00) in the morning was higher (1.2–1.3 times) than in the evening (20-00). In the presence of comorbid FM, patients with RA had significant increase in evening and average daily levels of IL-1β (1.3–1.6 times) than in RA patients without FM. Daily fluctuations of IL-1β correlate with RA activity and the fibromyalgia scale. Conclusions: In RA patients disorders of the circadian production of proinflammatory IL-1β, which are exacerbated under FM conditions, were detected. Increasing evening production of IL-1β correlated with the prevalence of pain index in RA patients with FM. Thus, disorders of IL-1β circadian production in RA patients can be integrated into the mechanisms of central sensitization and FM development.
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Barnea, Maayan, Zecharia Madar, and Oren Froy. "High-Fat Diet Delays and Fasting Advances the Circadian Expression of Adiponectin Signaling Components in Mouse Liver." Endocrinology 150, no. 1 (September 18, 2008): 161–68. http://dx.doi.org/10.1210/en.2008-0944.
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The circadian clock controls energy homeostasis by regulating circadian expression and/or activity of enzymes involved in metabolism. Disruption of circadian rhythms may lead to obesity and metabolic disorders. We tested whether the biological clock controls adiponectin signaling pathway in the liver and whether fasting and/or high-fat (HF) diet affects this control. Mice were fed low-fat or HF diet and fasted on the last day. The circadian expression of clock genes and components of adiponectin metabolic pathway in the liver was tested at the RNA, protein, or enzyme activity level. In addition, serum levels of glucose, adiponectin, and insulin were measured. Under low-fat diet, adiponectin signaling pathway components exhibited circadian rhythmicity. However, fasting and HF diet altered this circadian expression; fasting resulted in a phase advance, and HF diet caused a phase delay. In addition, adenosine monophosphate-activated protein kinase levels were high during fasting and low during HF diet. Changes in the phase and daily rhythm of clock genes and components of adiponectin signaling pathway as a result of HF diet may lead to obesity and may explain the disruption of other clock-controlled output systems, such as blood pressure and sleep/wake cycle, usually associated with metabolic disorders. Adiponectin signaling pathway components exhibit circadian rhythmicity under low-fat diet. Fasting and high-fat diet alter this circadian expression, leading to phase advance and delay, respectively.
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Evans, Jennifer A., Tanya L. Leise, Oscar Castanon-Cervantes, and Alec J. Davidson. "Neural correlates of individual differences in circadian behaviour." Proceedings of the Royal Society B: Biological Sciences 282, no. 1810 (July 7, 2015): 20150769. http://dx.doi.org/10.1098/rspb.2015.0769.
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Daily rhythms in mammals are controlled by the circadian system, which is a collection of biological clocks regulated by a central pacemaker within the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. Changes in SCN function have pronounced consequences for behaviour and physiology; however, few studies have examined whether individual differences in circadian behaviour reflect changes in SCN function. Here, PERIOD2::LUCIFERASE mice were exposed to a behavioural assay to characterize individual differences in baseline entrainment, rate of re-entrainment and free-running rhythms. SCN slices were then collected for ex vivo bioluminescence imaging to gain insight into how the properties of the SCN clock influence individual differences in behavioural rhythms. First, individual differences in the timing of locomotor activity rhythms were positively correlated with the timing of SCN rhythms. Second, slower adjustment during simulated jetlag was associated with a larger degree of phase heterogeneity among SCN neurons. Collectively, these findings highlight the role of the SCN network in determining individual differences in circadian behaviour. Furthermore, these results reveal novel ways that the network organization of the SCN influences plasticity at the behavioural level, and lend insight into potential interventions designed to modulate the rate of resynchronization during transmeridian travel and shift work.
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Shavlakadze, T., T. Anwari, Z. Soffe, G. Cozens, P. J. Mark, C. Gondro, and M. D. Grounds. "Impact of fasting on the rhythmic expression of myogenic and metabolic factors in skeletal muscle of adult mice." American Journal of Physiology-Cell Physiology 305, no. 1 (July 1, 2013): C26—C35. http://dx.doi.org/10.1152/ajpcell.00027.2013.
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Circadian rhythms and metabolism are tightly integrated, and rhythmic expression of metabolic factors is common in homeostatic processes. We measured the temporal changes in the expression of myogenic regulatory factors and expression and activity level of molecules involved in protein metabolism in skeletal muscles and livers in mice and examined the impact of fasting. Tissues were collected over 24 h (at zeitgeber times ZT1, ZT5, ZT9, ZT13, ZT17, ZT21, and ZT1 the following day) from adult male C57Bl/6J mice that had been either freely fed or fasted for 24 h. In skeletal muscle, there was a robust rise in the mRNA expression of the myogenic regulatory factors MyoD and myogenin during dark hours which was strongly suppressed by fasting. Circadian pattern was observed for mRNA of MuRF1, Akt1, and ribosomal protein S6 in muscles in fed and fasted mice and for Fbxo32 in fed mice. Activity (phosphorylation) levels of Akt(Ser473) displayed temporal regulation in fasted (but not fed) mice and were high at ZT9. Fasting caused significant reductions in phosphorylation for both Akt and S6 in muscles, indicative of inactivation. Hepatic phosphorylated Akt(Ser473) and S6(Ser235/236) proteins did not exhibit daily rhythms. Fasting significantly reduced hepatic Akt(473) phosphorylation compared with fed levels, although (unlike in muscle) it did not affect S6(Ser235/236) phosphorylation. This in vivo circadian study addresses for the first time the signaling activities of key molecules related to protein turnover and their possible cross-regulation of expression of genes related to protein degradation.
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Flôres, Danilo E. F. L., and Gisele A. Oda. "Quantitative Study of Dual Circadian Oscillator Models under Different Skeleton Photoperiods." Journal of Biological Rhythms 35, no. 3 (February 4, 2020): 302–16. http://dx.doi.org/10.1177/0748730420901939.
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The daily proportion of light and dark hours (photoperiod) changes annually and plays an important role in the synchronization of seasonal biological phenomena, such as reproduction, hibernation, and migration. In mammals, the first step of photoperiod transduction occurs in the suprachiasmatic nuclei (SCN), the circadian pacemaker that also coordinates 24-h activity rhythms. Thus, in parallel with its role in annual synchronization, photoperiod variation acutely shapes day/night activity patterns, which vary throughout the year. Systematic studies of this behavioral modulation help understand the mechanisms behind its transduction at the SCN level. To explain how entrainment mechanisms could account for daily activity patterns under different photoperiods, Colin Pittendrigh and Serge Daan proposed a conceptual model in which the pacemaker would be composed of 2 coupled, evening (E) and morning (M), oscillators. Although the E-M model has existed for more than 40 years now, its physiological bases are still not fully resolved, and it has not been tested quantitatively under different photoperiods. To better explore the implications of the E-M model, we performed computer simulations of 2 coupled limit-cycle oscillators. Four model configurations were exposed to systematic variation of skeleton photoperiods, and the resulting daily activity patterns were assessed. The criterion for evaluating different model configurations was the successful reproduction of 2 key behavioral phenomena observed experimentally: activity psi-jumps and photoperiod-induced changes in activity phase duration. We compared configurations with either separate light inputs to E and M or the same light inputs to both oscillators. The former replicated experimental results closely, indicating that the configuration with separate E and M light inputs is the mechanism that best reproduces the effects of different skeleton photoperiods on day/night activity patterns. We hope this model can contribute to the search for E and M and their light input organization in the SCN.
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Yang, Hui-Wen, Marta Garaulet, Peng Li, Cristina Bandin, Chen Lin, Men-Tzung Lo, and Kun Hu. "Daily Rhythm of Fractal Cardiac Dynamics Links to Weight Loss Resistance: Interaction with CLOCK 3111T/C Genetic Variant." Nutrients 13, no. 7 (July 19, 2021): 2463. http://dx.doi.org/10.3390/nu13072463.
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The effectiveness of weight loss treatment displays dramatic inter-individual variabilities, even with well-controlled energy intake/expenditure. This study aimed to determine the association between daily rhythms of cardiac autonomic control and weight loss efficiency and to explore the potential relevance to weight loss resistance in humans carrying the genetic variant C at CLOCK 3111T/C. A total of 39 overweight/obese Caucasian women (20 CLOCK 3111C carriers and 19 non-carriers) completed a behaviour–dietary obesity treatment of ~20 weeks, during which body weight was assessed weekly. Ambulatory electrocardiographic data were continuously collected for up to 3.5 days and used to quantify the daily rhythm of fractal cardiac dynamics (FCD), a non-linear measure of autonomic function. FCD showed a 24 h rhythm (p < 0.001). Independent of energy intake and physical activity level, faster weight loss was observed in individuals with the phase (peak) of the rhythm between ~2–8 p.m. and with a larger amplitude. Interestingly, the phase effect was significant only in C carriers (p = 0.008), while the amplitude effect was only significant in TT carriers (p < 0.0001). The daily rhythm of FCD and CLOCK 3111T/C genotype is linked to weight loss response interactively, suggesting complex interactions between the genetics of the circadian clock, the daily rhythm of autonomic control, and energy balance control.
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Huang, T., J. Chung, M. Reid, D. A. Johnson, M. E. Billings, E. B. Klerman, and S. Redline. "1007 Sociodemographic, Lifestyle and Dietary Correlates of Actigraphy-Measured Irregular Sleep Schedules in the Multi-Ethnic Study of Atherosclerosis." Sleep 43, Supplement_1 (April 2020): A382—A383. http://dx.doi.org/10.1093/sleep/zsaa056.1003.
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Abstract Introduction Increasing evidence links daily variability in sleep schedules to increased cardiometabolic risk. Little is known, however, regarding sociodemographic and behavioral correlates of irregular sleep schedules that may help identify causes or consequences of irregular sleep. Methods Among 1,946 participants from the Multi-Ethnic Study of Atherosclerosis, we examined the cross-sectional associations of irregular sleep schedules with sociodemographic, lifestyle, dietary factors, and actigraphy-based indices of rest-wake rhythms using multiple linear regression with adjustment for age, sex, race/ethnicity, education, income, marital status and work schedules. Sleep regularity was assessed using standard deviations (SD) in actigraphy-measured sleep duration and sleep onset timing across 7 days. Results Compared to Whites, the 7-day sleep duration SD (95% CI) was 17.4min (12.6, 22.2) higher in African-Americans, 10.4min (4.8, 16.0) higher in Hispanics and 7.9min (1.3, 14.4) higher in Chinese. Shift versus regular work was associated with 11.4min (5.1, 17.7) higher sleep duration SD. Irregular sleep duration was associated with lower income (p=0.006), higher depressive symptoms (p<0.0001), higher BMI (p=0.004) and current smoking (p=0.06). Higher sleep duration variability was associated with lower Alternative Healthy Eating Index (p=0.01), mainly due to suboptimal intakes of fruits, whole grains and nuts/legumes. No associations were observed for age, sex, education, marital status or number of meals per day. While sleep duration variability was not associated with self-reported physical activity level or actigraphy-measured 7-day mean activity count, sleep duration SD was inversely associated with relative amplitude (difference between the most versus the least active period; p<0.0001) and inter-daily stability (synchronization between rest-activity patterns and environmental zeitgebers; p<0.0001) of 24-h rest-activity patterns. Similar results were observed for sleep onset timing SD. Conclusion Substantial differences by sociodemographic factors exist regarding the consistency of day-to-day sleep schedules. Irregular sleep schedules are associated with overall circadian disruption across the day and some unhealthy lifestyle behaviors. Future studies are needed to understand temporal relationships of the observed associations. Support NIH grants K01HL143034, R35HL135818
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Hor, Charlotte N., Jake Yeung, Maxime Jan, Yann Emmenegger, Jeffrey Hubbard, Ioannis Xenarios, Felix Naef, and Paul Franken. "Sleep–wake-driven and circadian contributions to daily rhythms in gene expression and chromatin accessibility in the murine cortex." Proceedings of the National Academy of Sciences 116, no. 51 (November 27, 2019): 25773–83. http://dx.doi.org/10.1073/pnas.1910590116.
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The timing and duration of sleep results from the interaction between a homeostatic sleep–wake-driven process and a periodic circadian process, and involves changes in gene regulation and expression. Unraveling the contributions of both processes and their interaction to transcriptional and epigenomic regulatory dynamics requires sampling over time under conditions of unperturbed and perturbed sleep. We profiled mRNA expression and chromatin accessibility in the cerebral cortex of mice over a 3-d period, including a 6-h sleep deprivation (SD) on day 2. We used mathematical modeling to integrate time series of mRNA expression data with sleep–wake history, which established that a large proportion of rhythmic genes are governed by the homeostatic process with varying degrees of interaction with the circadian process, sometimes working in opposition. Remarkably, SD caused long-term effects on gene-expression dynamics, outlasting phenotypic recovery, most strikingly illustrated by a damped oscillation of most core clock genes, includingArntl/Bmal1, suggesting that enforced wakefulness directly impacts the molecular clock machinery. Chromatin accessibility proved highly plastic and dynamically affected by SD. Dynamics in distal regions, rather than promoters, correlated with mRNA expression, implying that changes in expression result from constitutively accessible promoters under the influence of enhancers or repressors. Serum response factor (SRF) was predicted as a transcriptional regulator driving immediate response, suggesting that SRF activity mirrors the build-up and release of sleep pressure. Our results demonstrate that a single, short SD has long-term aftereffects at the genomic regulatory level and highlights the importance of the sleep–wake distribution to diurnal rhythmicity and circadian processes.
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Sundar, Isaac K., Hongwei Yao, Michael T. Sellix, and Irfan Rahman. "Circadian molecular clock in lung pathophysiology." American Journal of Physiology-Lung Cellular and Molecular Physiology 309, no. 10 (November 15, 2015): L1056—L1075. http://dx.doi.org/10.1152/ajplung.00152.2015.
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Disrupted daily or circadian rhythms of lung function and inflammatory responses are common features of chronic airway diseases. At the molecular level these circadian rhythms depend on the activity of an autoregulatory feedback loop oscillator of clock gene transcription factors, including the BMAL1:CLOCK activator complex and the repressors PERIOD and CRYPTOCHROME. The key nuclear receptors and transcription factors REV-ERBα and RORα regulate Bmal1 expression and provide stability to the oscillator. Circadian clock dysfunction is implicated in both immune and inflammatory responses to environmental, inflammatory, and infectious agents. Molecular clock function is altered by exposomes, tobacco smoke, lipopolysaccharide, hyperoxia, allergens, bleomycin, as well as bacterial and viral infections. The deacetylase Sirtuin 1 (SIRT1) regulates the timing of the clock through acetylation of BMAL1 and PER2 and controls the clock-dependent functions, which can also be affected by environmental stressors. Environmental agents and redox modulation may alter the levels of REV-ERBα and RORα in lung tissue in association with a heightened DNA damage response, cellular senescence, and inflammation. A reciprocal relationship exists between the molecular clock and immune/inflammatory responses in the lungs. Molecular clock function in lung cells may be used as a biomarker of disease severity and exacerbations or for assessing the efficacy of chronotherapy for disease management. Here, we provide a comprehensive overview of clock-controlled cellular and molecular functions in the lungs and highlight the repercussions of clock disruption on the pathophysiology of chronic airway diseases and their exacerbations. Furthermore, we highlight the potential for the molecular clock as a novel chronopharmacological target for the management of lung pathophysiology.
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Lim, Ji Ye, Eunju Kim, Collin M. Douglas, Marvin Wirianto, Chorong Han, Kaori Ono, Sun Young Kim, et al. "The circadian E3 ligase FBXL21 regulates myoblast differentiation and sarcomere architecture via MYOZ1 ubiquitination and NFAT signaling." PLOS Genetics 18, no. 12 (December 27, 2022): e1010574. http://dx.doi.org/10.1371/journal.pgen.1010574.
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Numerous molecular and physiological processes in the skeletal muscle undergo circadian time-dependent oscillations in accordance with daily activity/rest cycles. The circadian regulatory mechanisms underlying these cyclic processes, especially at the post-transcriptional level, are not well defined. Previously, we reported that the circadian E3 ligase FBXL21 mediates rhythmic degradation of the sarcomere protein TCAP in conjunction with GSK-3β, and Psttm mice harboring an Fbxl21 hypomorph allele show reduced muscle fiber diameter and impaired muscle function. To further elucidate the regulatory function of FBXL21 in skeletal muscle, we investigated another sarcomere protein, Myozenin1 (MYOZ1), that we identified as an FBXL21-binding protein from yeast 2-hybrid screening. We show that FBXL21 binding to MYOZ1 led to ubiquitination-mediated proteasomal degradation. GSK-3β co-expression and inhibition were found to accelerate and decelerate FBXL21-mediated MYOZ1 degradation, respectively. Previously, MYOZ1 has been shown to inhibit calcineurin/NFAT signaling important for muscle differentiation. In accordance, Fbxl21 KO and MyoZ1 KO in C2C12 cells impaired and enhanced myogenic differentiation respectively compared with control C2C12 cells, concomitant with distinct effects on NFAT nuclear localization and NFAT target gene expression. Importantly, in Psttm mice, both the levels and diurnal rhythm of NFAT2 nuclear localization were significantly diminished relative to wild-type mice, and circadian expression of NFAT target genes associated with muscle differentiation was also markedly dampened. Furthermore, Psttm mice exhibited significant disruption of sarcomere structure with a considerable excess of MYOZ1 accumulation in the Z-line. Taken together, our study illustrates a pivotal role of FBXL21 in sarcomere structure and muscle differentiation by regulating MYOZ1 degradation and NFAT2 signaling.
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Cannizzaro, Emanuele, Luigi Cirrincione, Walter Mazzucco, Alessandro Scorciapino, Cesare Catalano, Tiziana Ramaci, Caterina Ledda, and Fulvio Plescia. "Night-Time Shift Work and Related Stress Responses: A Study on Security Guards." International Journal of Environmental Research and Public Health 17, no. 2 (January 15, 2020): 562. http://dx.doi.org/10.3390/ijerph17020562.
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Work-related stress can induce a break in homeostasis by placing demands on the body that are met by the activation of two different systems, the hypothalamic–pituitary–adrenal axis and the sympathetic nervous system. Night-shift work alters the body’s exposure to the natural light–dark schedule and disrupts circadian (daily) rhythms. The greatest effect of night-shift work is the disruption of circadian rhythms. The impact that these disruptions may have on the pathogenesis of many diseases, including cancer, is unknown. This study aims to discover the relationship among three different job activities of security guards and their stress-related responses by evaluating salivary cortisol levels and blood pressure. Methods: Ninety security guards, including night-time workers and night-time and daily-shift workers, were recruited for this study. Each security guard provided two saliva samples before and after three scheduled time points: (i) at 22:00, (ii) at 06:30, and (iii) at 14:00. Results: The results of the study showed a significant alteration in cortisol levels. Night-time shift cortisol levels significantly increased before and after the work shifts. A physiological prevalence of the vagal tone on the cardiocirculatory activity was found during night-shift work. Conclusions: This study indicates that cortisol levels and blood pressure are sensitive markers of biological responses to severe work stress. Shift-change consequences may occur at the end of the night shift when there is a significant increase in the cortisol level and a significant variation in cardiovascular parameters.
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Nechitaylo, Yuriy, Oleksandr Buriak, Olesya Pidmurniak, Nataliya Kovtyuk, and Tatiana Fomina. "VARIABILITY OF ARTERIAL BLOOD PRESSURE IN CHILDREN WITH DIABETES MELLITUS AND OBESITY." CBU International Conference Proceedings 7 (September 30, 2019): 778–82. http://dx.doi.org/10.12955/cbup.v7.1454.
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INTRODUCTION: The activity of the cardiovascular system has a clear to the circadian rhythms of a child's body. Daily fluctuations in blood pressure in normal conditions and in pathology is a physiological phenomenon which can play a significant role in developing arterial hypertension and even in the occurrence of fatal cardiovascular states such as heart attacks, strokes, and sudden cardiac arrest activities. Ambulatory blood pressure monitoring is recognized as a necessary instrumental investigation for diagnosis and management of patients with arterial hypertension and especially in children from high risk groups such as diabetics and obesity it may be even more important for hypertension diagnostics than in adults.
AIM: The objective of the study was to analyze the features of circadian oscillations of blood pressure and heart rate variability in children with diabetes mellitus and hypothalamic syndrome with obesity.
METHODS: Research included 76 children aged 10 to 18 years: 52 children with endocrine pathology (diabetes and obesity) and 24 clinically healthy persons. The peculiarities of nutrition, sleep, and the definition of the chronotype using the Horn-Ostberg questionnaire were carried out. The functional state of the cardiovascular systems was determined by single office measurement and by ambulatory blood pressure monitoring.
FINDINGS AND RESULTS: Ambulatory blood pressure monitoring revealed a number of differences between the groups of children. In diabetic patients, daytime systolic blood pressure was higher with increased variability, while the night blood pressure was significantly lower and with significantly less variability, compared to other groups. Attention is drawn to the higher level of diastolic blood pressure and lower variability at night in obese children.
CONCLUSIONS: Daily fluctuations of arterial pressure in children with diabetes and obesity differ from healthy persons depending on the type of disease and could be regarded as result of circadian biorhythms disruption. In obese persons it appears in the form of nocturnal SBP and DBP elevation but with index of variability compared to the control group. In diabetic children the circadian BP rhythms deviations appear in form of SBP elevation during the day with higher index of its variability. Their BP changes were associated with the presence of diabetic nephropathy and proteinuria.
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Bulyk, R. Y., A. V. Abramov, T. S. Bulyk, M. I. Kryvchanska, and K. V. Vlasova. "The effects of melatonin on the activity of the c-fos gene in the structures of the hypothalamic paraventricular nucleus under prolonged lighting." Regulatory Mechanisms in Biosystems 9, no. 2 (March 17, 2018): 131–34. http://dx.doi.org/10.15421/021819.
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The effect of constant illumination as a stress factor on the state of the "early response" c-fos gene in the lateral magnocellular subnuclei of the paraventricular nucleus (lmPVN) of the hypothalamus of rats at different time intervals (day and night) has been studied. To identify c-Fos in histological sections of the hypothalamus, a secondary (indirect) immunofluorescence method is used. Expression of the product of this gene, the c-Fos protein, in animals kept under normal conditions of alternation of illumination and darkness, shows a clear-cut circadian character. There was a significant decrease in the area of the immunopositive sites of structures at night by 19.4% compared to daytime measurements. The average values of the areas of such immunopositive subnuclei sites varied also in subgroups of rats under light stimulation conditions, in which samples of lmPVN were selected for study at 2 pm and 2 am, but the differences between groups did not reach the level of reliability. Under conditions of light stress, the c-Fos concentration index decreased by 29.4% during the day, and by 16.5% at night in relation to similar values in the intact group. In animals that were in the standard light mode, the c-Fos protein concentration index was significantly higher during the day than at night. In the intact group, the night value of the c-Fos concentration index averaged only 71.5% of the daily value. In rats subjected to constant illumination, the day and night values of the c-Fos concentration index did not differ reliably. To correct stress-induced changes in the activity of the "early response" c-fos gene in the rat hypothalamus, melatonin (0.5 mg/kg body weight of the animal) was used. Injections of melatonin to rats exposed to constant illumination normalized the circadian rhythm of the area of the material immunoreactive to c-Fos, compared to the group of animals that did not receive melatonin. When using melatonin against the background of constant illumination, a sharp increase of the protein concentration in the lmPVN subnuclei of hypothalamus in daytime and less pronounced at night intervals was detected. Injections of melatonin to animals were also reflected in the daily dynamics of the index of c-Fos protein content in the lmPVN subnuclei under conditions of constant illumination. In the daytime observation period, the index was almost twice the experimental data on stressed animals without the introduction of the hormone, bringing it closer to normal. Prospects for further research in this sphere will allow us to better understand the place and role of subnuclei of paraventricular nuclei of the hypothalamus in the mechanisms of the formation of circadian rhythms of the rat brain.
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Yang, Hui-Wen, Peng Li, Haoqi Sun, Matthew Maher, Jacqueline Lane, Andrew Lim, David Bennett, et al. "0195 Integrated actigraphy-based biomarker for the risk of Alzheimer’s dementia." Sleep 45, Supplement_1 (May 25, 2022): A89. http://dx.doi.org/10.1093/sleep/zsac079.193.
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Abstract Introduction Many physiological measures derived from actigraphy including physical activity, sleep, circadian/daily rhythm, and temporal correlations have been shown to predict Alzheimer’s dementia (AD). This study aimed to combine these actigraphy-based measures to develop an integrated actigraphy biomarker (IAB) for AD and to test its link to the genetic risk for AD. Methods We analyzed data of 1107 participants (age 80.9±7.3(mean±SD)) from the Rush Memory and Aging Project who were non-demented and had actigraphy (~10 days) at baseline, and had annual cognitive assessment during the follow-up (1-15 years). 270 developed AD (mean = 7.4 years). To construct the IAB for the AD’s risk, we trained a random forest survival model, in which time to incident AD was the outcome, and inputs included 10 features derived from actigraphy data: physical activity level, 3 features for sleep (sleep duration, sleep fragmentation, activity fragmentation), 4 features for circadian rhythmicity (amplitude, acrophase, interdaily stability, and intradaily variability of 24-hr rhythms), and 2 features for temporal correlations (at timescales between 1-90 min and 120-480 min). Polygenic risk score (PRS) was calculated using 457 independent SNPs strongly associated with Alzheimer’s disease (p<0.001). Cox proportional hazard ratio models were performed with different combinations of IAB, PRS, age, sex, and education, and the concordance score (C-score) was used to evaluate model performance. Results The derived IAB was 0.6 SD larger in the AD group as compared with the controls. The IAB alone achieved a C-score = 0.61 in predicting AD, with a hazard ratio=1.5 for 1-SD increase in IAB. The IAB and PRS were not correlated (r2=0.0004, p=0.25), and both significantly contributed to the prediction (both p<=0.0001) when included in one model, giving a C-score of 0.65. C-score was 0.7 in the model using only age, sex and educations yielded, and increased to 0.74 after including IAB and PRS (both effects remained significant p<0.0001). Conclusion The integrated actigraphy biomarker may provide complementary information for early prediction and detection of AD, independent of the known demographic and genetic risk factors. Support (If Any) NIH (RF1AG064312, RF1AG059867, R01AG56352, R01AG17917, T32GM007592, and R03AG067985); The BrightFocus Foundation (A2020886S).
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Zaichko, K., M. Stanislavchuk, N. Zaichko, and V. Khomenko. "FRI0025 CIRCADIAN RHYTHMS OF ENDOTHELIAL NITRIC OXIDE SYNTHASE PRODUCTION IN FEMALES WITH RHEUMATOID ARTHRITIS AND ARTERIAL HYPERTENSION DEPENDING ON NOS3 Т786С GENE POLYMORPHISM." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 585.2–585. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4254.
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Background:One of the most common comorbidity in patients with rheumatoid arthritis (RA) is arterial hypertension (AH), with incidence ranging from 20 to 60%. Mechanisms of this comorbidity arises a lot of interest. In our previous study was established the association ofT786C NOS3(rs2070744) gene polymorphism with AH in females with RA in the Ukrainian population [1].Objectives:So next, we were aiming to investigate daily fluctuation of endothelial nitric oxide synthase (NOS3) in RA patients with AH depending onNOS3 T786Cgene polymorphism.Methods:In the study were enrolled 173 females with RA aged 43.7 ± 7.35 years (Mean ± SD) and 34 age-matched healthy women without joint diseases and autoimmune diseases (control). Serum NOS3 level was determined at 08:00 and 20:00 using Cloud-Clone Corp kits (USA).NOS3 T-786Сpolymorphism was determined by Real-Time PCR (Bio-Rad iCycler IQ5) using SNP-express kit. Study was carried out in compliance with bioethical standards and provisions of the WHO, Helsinki Declaration of the General Assembly of the World Medical Association (1989).Results:Among enrolled patients prevailed individuals with more than 5 years disease history, ІІ-ІІІ radiographic stage (80.9 %), and were seropositive for anti-cyclic citrullinated peptide (80.6%). There were 114 (66%) normotensive patients and 59 (34%) patients with AH (13% - I stage, 20.8% - II stage). The daily fluctuation of NOS3 serum level was established in the control group. The evening NOS3 level was higher in 1.3 times, than the morning level (р<0.001). In RA patients the similar fluctuations of NOS3 level was registered, but the daily NOS3 production was lower, than in control. Diurnal variation of NOS3 level depended on comorbid AH andNOS3 T-786Сgenotype. InCCgenotype NOS3 levels at 08:00 and at 20:00 were lower in 1.2-1.3 times (p<0.05) than inTTandTCgenotypes. In patients with RA and AH the lowest diurnal variation of NOS3 level was inCCgenotype. The decrease of evening NOS3 production was strong associated with comorbid AH (OR 3.78; 95% CI 1.96-7.28).Conclusion:Circadian rhythms of NOS3 production in females with RA and AH depend onNOS3 Т786Сgene polymorphism. The depression of NOS3 production in the evening can be predictor of comorbid AH in females with RA.References:[1]Zaichko, K., & Stanislavchuk, M. (2017, April). T-786C gene promoter polymorphism of endothelial nitric oxide synthase: its association to the disease activity and arterial hypertension in patients with rheumatoid arthritis in the ukraine population. In rheumatology (vol. 56, pp. 129-129). GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND: OXFORD UNIV PRESS.Acknowledgments:NADisclosure of Interests:None declared
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Zaichko, K., and N. Zaichko. "POS0622 ASSOCIATION OF DIURNAL FLUCTUATION OF THE SOLUBLE TOLL-LIKE RECEPTORS 2 (sTLR2) WITH COMORBIDITY AND QUALITY OF LIFE IN WOMEN WITH RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 579.1–579. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3955.
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BackgroundDisorders of circadian rhythms in the production of inflammatory mediators play an important role in the pathogenesis of rheumatoid arthritis (RA) [1]. Innate immune factors, in particular toll-like receptors 2 (TLR2), are involved in the formation of the inflammatory pattern in RA. Recently was shown that TLR2 play an important role in the development of atherosclerosis and hypertension [2]. Chronobiological aspects of innate immunity, in particular circadian rhythms of the soluble form of TLR2 (sTLR2) in RA and its comorbidity, requires further study.ObjectivesThe aim of the study was to assess the daily variability of sTLR2 in RA patients depending on comorbid conditions and quality of life indexes.MethodsIn the study were enrolled 173 females with RA aged 45.9 (8.79) years and disease duration 7.96 (6.38) years. High activity of the RA (DAS28-ESR > 5.1) were registered in 114 (66%) cases, moderate activity (DAS-28 3.2-5.1) - in 59 (34%) cases. 144 (83%) patients were seropositive by anticyclic citrullinated peptide (ACCP). Among enrolled subjects 140 (81%) had ІІ-ІІІ radiographic stage. There were 89 (51%) patients with comorbid pathology, including arterial hypertension (AH) - 59 (34%). Serum sTLR2 level was determined at 8:00 and 20:00 using Cloud-Clone Corp kits (USA). All stages of the study were carried out in compliance with bioethical standards and provisions of the WHO, Helsinki Declaration of the General Assembly of the World Medical Association (1989), Bioethical protocol No 1, 01 November 2016. *Data are mean (SD) or n (%).ResultsIn patients with RA, daily fluctuations in sTLR2 levels were detected: indexes at 8:00 at 20:00 were lower than at 8:00 (343 (93.7) vs 272 (99.2) ng/L, р<0.001). The mean difference between sTLR2 levels at 8:00 and 20:00 was -21.6 (13.2) %. In RA patients with AH, the average daily level of sTLR2 was higher (in 1.42 times, p <0.001) than in RA patients without AH. Differences between RA with AH and RA without AH groups were more significant in the evening sTLR2 level (320 (112) vs 246 (81.3) ng/L, р<0.01), than in the morning (378 (90.6) vs 321 (89.0) ng/L, р<0.05). In the group RA with AH decrease in sTLR2 in the evening was less than in the group RA without AH (1.36 times, p <0.05). An increase in sTLR2 at 20:00 was associated with a deterioration in mental health according to SF-36 (VT, SF, MH) in 1.2-1.3 times (highest quartile vs lowest quartile, р<0.01). An increase in sTLR2 at 8:00 was associated with a decrease in physical health PF, RP, BP and GH (in 1.3-1.6 times, р<0.01). Patients with high levels of sTLR2 showed more severe pain, impaired function, fatigue and sleep, decreased physical and emotional comfort, and control of symptoms according to RAID (in 1.3-1.4 times, р<0.01).ConclusionIn RA patients daily fluctuations in sTLR2 levels has been registered with the decrease of this index in the evening. In the case of comorbid AH production of sTLR2 is higher, especially in the evening time. Disorders of sTLR2 production are one of the factors that deteriorate the quality of life in patients with RA.References[1]Cutolo M. (2016) Glucocorticoids and chronotherapy in rheumatoid arthritis. RMD Open, 2:e000203. doi:10.1136/rmdopen-2015-000203[2]Lazaridis A., Gavriilaki E., Douma S., & Gkaliagkousi E. (2021) Toll-like receptors in the pathogenesis of essential hypertension. a forthcoming immune-driven theory in full effect. Int J Mol Sci, 22(7):3451. doi: 10.3390/ijms22073451.Disclosure of InterestsNone declared
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Nechytailo, D., T. Mikheeva, and O. Hodovanets. "CHRONOBIOLOGICAL ASPECTS OF ARTERIAL PRESSURE LEVEL IN SCHOOLCHILDREN WITH ARTERIAL PREHYPERTENSION." Neonatology, surgery and perinatal medicine 12, no. 1(43) (May 8, 2022): 37–42. http://dx.doi.org/10.24061/2413-4260.xii.1.43.2022.7.
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Introduction. Arterial pressure has significant diurnal fluctuations, reaching its minimum and maximum values at certain hours of the day. For a complete characterization of arterial hypertension in recent years, the method of daily monitoring of arterial pressure is most often used, which makes it possible to determine the forms of the disease (labile and stable), circadian rhythms of arterial pressure and its variability. The use of this method in children may be even more important than in adults.Aim: to evaluate the chronobiological aspects of the level of arterial pressure in schoolchildren with arterial prehypertension.Materials and methods. 54 school-age children were examined, who were divided into the following groups: the main group consisted of 24 children with arterial prehypertension (high blood pressure) and the control group - 30 children with normal blood pressure.Chronobiological aspects of the level of arterial pressure in schoolchildren were assessed using daily monitoring of arterial pressure. The 24-hour blood pressure device provided long-term recording of blood pressure fluctuations during normal 24-hour activity and during patient’s sleep.Statistical processing of the obtained data was carried out using Microsoft Office Excel and Statistica 10.0 applications. Research results. When evaluating the characteristics of time indices of blood pressure in the examined children, it was found that children with prehypertension most often had an increase in systolic blood pressure at night.Comparing the features of daily blood pressure fluctuations between children with prehypertension and children from the control group, certain differences were identified that were observed in the curves of systolic blood pressure and diastolic blood pressure, especially at night.When assessing the variability of the average daily and average night levels of systolic and diastolic blood pressure in children by groups, it was found that the variability of systolic and diastolic blood pressure in children with prehypertension was probably lower than in children from the control group.Additionally, the features of the daily fluctuations in mean arterial pressure were evaluated, because it simultaneously takes into account the daily fluctuations of both systolic and diastolic blood pressure. The T-test showed that the mean arterial pressure level was probably higher in children with prehypertension (p<0,05) compared to children from the control group.Conclusions.1. There is a phenomenon of a decrease in blood pressure variability in children with prehypertension (especially at night), which can be regarded as a risk factor for the development of arterial hypertension.2. Based on the presence of a probable difference in the indicators of daily fluctuations in mean arterial pressure among children from the control group and children with prehypertension, the latter have an increase in the dynamic load on the vascular wall, which can lead to a slowdown in the blood flow velocity in the capillary bed and also act as a predictor of arterial hypertension.
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Chaibub Neto, Elias, Thanneer M. Perumal, Abhishek Pratap, Aryton Tediarjo, Brian M. Bot, Lara Mangravite, and Larsson Omberg. "Disentangling personalized treatment effects from “time-of-the-day” confounding in mobile health studies." PLOS ONE 17, no. 8 (August 4, 2022): e0271766. http://dx.doi.org/10.1371/journal.pone.0271766.
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Ideally, a patient’s response to medication can be monitored by measuring changes in performance of some activity. In observational studies, however, any detected association between treatment (“on-medication” vs “off-medication”) and the outcome (performance in the activity) might be due to confounders. In particular, causal inferences at the personalized level are especially vulnerable to confounding effects that arise in a cyclic fashion. For quick acting medications, effects can be confounded by circadian rhythms and daily routines. Using the time-of-the-day as a surrogate for these confounders and the performance measurements as captured on a smartphone, we propose a personalized statistical approach to disentangle putative treatment and “time-of-the-day” effects, that leverages conditional independence relations spanned by causal graphical models involving the treatment, time-of-the-day, and outcome variables. Our approach is based on conditional independence tests implemented via standard and temporal linear regression models. Using synthetic data, we investigate when and how residual autocorrelation can affect the standard tests, and how time series modeling (namely, ARIMA and robust regression via HAC covariance matrix estimators) can remedy these issues. In particular, our simulations illustrate that when patients perform their activities in a paired fashion, positive autocorrelation can lead to conservative results for the standard regression approach (i.e., lead to deflated true positive detection), whereas negative autocorrelation can lead to anticonservative behavior (i.e., lead to inflated false positive detection). The adoption of time series methods, on the other hand, leads to well controlled type I error rates. We illustrate the application of our methodology with data from a Parkinson’s disease mobile health study.
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Fujioka, Haruna, Masato S. Abe, and Yasukazu Okada. "Individual Ants Do Not Show Activity-Rest Rhythms in Nest Conditions." Journal of Biological Rhythms 36, no. 3 (April 5, 2021): 297–310. http://dx.doi.org/10.1177/07487304211002934.
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Circadian rhythms, which respond to the day-night cycle on the earth, arise from the endogenous timekeeping system within organisms, called the “biological clock.” For accurate circadian rhythms, daily fluctuations in light and temperature are considered one of the important time cues. In social insects, both abiotic and biotic factors (i.e., social interactions) play a significant role in activity-rest rhythm regulation. However, it is challenging to monitor individual activity-rest rhythms in a colony because of the large group size and small body size. Therefore, it is unclear whether individuals in a colony exhibit activity-rest rhythms and how social interactions regulate their activity-rest rhythms in the colony. This study developed an image-based tracking system using 2D barcodes for Diacamma cf. indicum from Japan (a monomorphic ant) and measured the locomotor activities of all colony members under laboratory colony conditions. We also investigated the effect of broods on activity-rest rhythms by removing all broods under colony conditions. Activity-rest rhythms appeared only in isolated ants, not under colony conditions. In addition, workers showed arrhythmic activities after brood removal. These results suggested that a mixture of social interactions, and not light and temperature, induces the loss of activity-rest rhythms. These results contribute to the knowledge of a diverse pattern of circadian activity rhythms in social insects.
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Ingram, Krista K., Deborah M. Gordon, Daniel A. Friedman, Michael Greene, John Kahler, and Swetha Peteru. "Context-dependent expression of the foraging gene in field colonies of ants: the interacting roles of age, environment and task." Proceedings of the Royal Society B: Biological Sciences 283, no. 1837 (August 31, 2016): 20160841. http://dx.doi.org/10.1098/rspb.2016.0841.
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Task allocation among social insect workers is an ideal framework for studying the molecular mechanisms underlying behavioural plasticity because workers of similar genotype adopt different behavioural phenotypes. Elegant laboratory studies have pioneered this effort, but field studies involving the genetic regulation of task allocation are rare. Here, we investigate the expression of the foraging gene in harvester ant workers from five age- and task-related groups in a natural population, and we experimentally test how exposure to light affects foraging expression in brood workers and foragers. Results from our field study show that the regulation of the foraging gene in harvester ants occurs at two time scales: levels of foraging mRNA are associated with ontogenetic changes over weeks in worker age, location and task, and there are significant daily oscillations in foraging expression in foragers. The temporal dissection of foraging expression reveals that gene expression changes in foragers occur across a scale of hours and the level of expression is predicted by activity rhythms: foragers have high levels of foraging mRNA during daylight hours when they are most active outside the nests. In the experimental study, we find complex interactions in foraging expression between task behaviour and light exposure. Oscillations occur in foragers following experimental exposure to 13 L : 11 D (LD) conditions, but not in brood workers under similar conditions. No significant differences were seen in foraging expression over time in either task in 24 h dark (DD) conditions. Interestingly, the expression of foraging in both undisturbed field and experimentally treated foragers is also significantly correlated with the expression of the circadian clock gene, cycle . Our results provide evidence that the regulation of this gene is context-dependent and associated with both ontogenetic and daily behavioural plasticity in field colonies of harvester ants. Our results underscore the importance of assaying temporal patterns in behavioural gene expression and suggest that gene regulation is an integral mechanism associated with behavioural plasticity in harvester ants.
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Brüning, Franziska, Sara B. Noya, Tanja Bange, Stella Koutsouli, Jan D. Rudolph, Shiva K. Tyagarajan, Jürgen Cox, Matthias Mann, Steven A. Brown, and Maria S. Robles. "Sleep-wake cycles drive daily dynamics of synaptic phosphorylation." Science 366, no. 6462 (October 10, 2019): eaav3617. http://dx.doi.org/10.1126/science.aav3617.
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The circadian clock drives daily changes of physiology, including sleep-wake cycles, through regulation of transcription, protein abundance, and function. Circadian phosphorylation controls cellular processes in peripheral organs, but little is known about its role in brain function and synaptic activity. We applied advanced quantitative phosphoproteomics to mouse forebrain synaptoneurosomes isolated across 24 hours, accurately quantifying almost 8000 phosphopeptides. Half of the synaptic phosphoproteins, including numerous kinases, had large-amplitude rhythms peaking at rest-activity and activity-rest transitions. Bioinformatic analyses revealed global temporal control of synaptic function through phosphorylation, including synaptic transmission, cytoskeleton reorganization, and excitatory/inhibitory balance. Sleep deprivation abolished 98% of all phosphorylation cycles in synaptoneurosomes, indicating that sleep-wake cycles rather than circadian signals are main drivers of synaptic phosphorylation, responding to both sleep and wake pressures.
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Slyepchenko, Anastasiya, Olivia R. Allega, Xiamin Leng, Luciano Minuzzi, Maha M. Eltayebani, Matthew Skelly, Roberto B. Sassi, Claudio N. Soares, Sidney H. Kennedy, and Benicio N. Frey. "Association of functioning and quality of life with objective and subjective measures of sleep and biological rhythms in major depressive and bipolar disorder." Australian & New Zealand Journal of Psychiatry 53, no. 7 (February 13, 2019): 683–96. http://dx.doi.org/10.1177/0004867419829228.
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Objective: Disruptions in biological rhythms and sleep are a core aspect of mood disorders, with sleep and rhythm changes frequently occurring prior to and during mood episodes. Wrist-worn actigraphs are increasingly utilized to measure ambulatory activity rhythm and sleep patterns. Methods: A comprehensive study using subjective and objective measures of sleep and biological rhythms was conducted in 111 participants (40 healthy volunteers [HC], 38 with major depressive disorder [MDD] and 33 with bipolar disorder [BD]). Participants completed 15-day actigraphy and first-morning urine samples to measure 6-sulfatoxymelatonin levels. Sleep and biological rhythm questionnaires were administered: Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), Munich Chronotype Questionnaire (MCTQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Actigraph data were analyzed for sleep and daily activity rhythms, light exposure and likelihood of transitioning between rest and activity states. Results: Mood groups had worse subjective sleep quality (PSQI) and biological rhythm disruption (BRIAN) and higher objective mean nighttime activity than controls. Participants with BD had longer total sleep time, higher circadian quotient and lower 6-sulfatoxymelatonin levels than HC group. The MDD group had longer sleep onset latency and higher daytime probability of transitioning from rest to activity than HCs. Mood groups displayed later mean timing of light exposure. Multiple linear regression analysis with BRIAN scores, circadian quotient, mean nighttime activity during rest and daytime probability of transitioning from activity to rest explained 43% of variance in quality-of-life scores. BRIAN scores, total sleep time and probability of transitioning from activity to rest explained 52% of variance in functioning (all p < 0.05). Conclusions: Disruption in biological rhythms is associated with poorer functioning and quality of life in bipolar and MDD. Investigating biological rhythms and sleep using actigraphy variables, urinary 6-sulfatoxymelatonin and subjective measures provide evidence of widespread sleep and circadian system disruptions in mood disorders.
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Helfrich-Förster, Charlotte, Michael N. Nitabach, and Todd C. Holmes. "Insect circadian clock outputs." Essays in Biochemistry 49 (June 30, 2011): 87–101. http://dx.doi.org/10.1042/bse0490087.
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Insects display an impressive variety of daily rhythms, which are most evident in their behaviour. Circadian timekeeping systems that generate these daily rhythms of physiology and behaviour all involve three interacting elements: the timekeeper itself (i.e. the clock), inputs to the clock through which it entrains and otherwise responds to environmental cues such as light and temperature, and outputs from the clock through which it imposes daily rhythms on various physiological and behavioural parameters. In insects, as in other animals, cellular clocks are embodied in clock neurons capable of sustained autonomous circadian rhythmicity, and those clock neurons are organized into clock circuits. Drosophila flies spend their entire lives in small areas near the ground, and use their circadian brain clock to regulate daily rhythms of rest and activity, so as to organize their behaviour appropriately to the daily rhythms of their local environment. Migratory locusts and butterflies, on the other hand, spend substantial portions of their lives high up in the air migrating long distances (sometimes thousands of miles) and use their circadian brain clocks to provide time-compensation to their sun-compass navigational systems. Interestingly, however, there appear to be substantial similarities in the cellular and network mechanisms that underlie circadian outputs in all insects.
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Hoopes, Elissa, Michele D'Agata, Talia Brookstein-Burke, Shannon Robson, Melissa Witman, Susan Malone, and Freda Patterson. "0003 On the Same Wavelength? Quantifying the Associations between Eating Timing and Rest-Activity Rhythms in Free-Living Adults." Sleep 45, Supplement_1 (May 25, 2022): A1—A2. http://dx.doi.org/10.1093/sleep/zsac079.002.
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Abstract Introduction Misalignment between the central circadian clock and daily behaviors increases cardiometabolic morbidity and mortality risk, likely due to internal misalignment between central and peripheral circadian rhythms. Experimental studies suggest food intake may act as a time cue (‘zeitgeber’) for resetting circadian rhythms, representing a potential behavioral target to ameliorate circadian misalignment and associated health consequences. However, the extent to which eating timing relates to circadian rhythms in free-living adults is unclear. Therefore, we tested the associations between eating timing with 24-h rest-activity-rhythms (RAR), a free-living proxy for endogenous circadian rhythms, in non-shift-working adults. Methods Adults without chronic health conditions or sleep disorders completed 14 days of 24/7 wrist accelerometry to evaluate RAR variables of interdaily stability (IS; day-to-day stability in RAR), intradaily variability (IV; within-day fragmentation of RAR), relative amplitude (RA; difference between peak vs. trough activity), L5 onset time (5-h period with lowest activity), and M10 onset time (10-h period with highest activity). Concurrently, time-stamped image-assisted diet records were obtained to generate average eating timing variables, including daily eating onset (time of first caloric intake after awakening), offset (last caloric intake time), duration (time elapsed between eating onset and offset), and caloric midpoint (time at which 50% of daily kcals were consumed), and variables illustrating irregularity in eating timing (standard deviation of eating timing variables). Pearson’s correlations quantified the associations between RAR and eating timing variables. Results Participants (N=30) were 28.0±6.6 years, 57% female, with a BMI of 23.8±2.5 kg/m2. Higher IS was correlated with lower irregularity in both eating onset (r=-0.55, p<0.01) and duration (r=-0.51, p<0.01). Higher RA correlated with earlier eating onset (r=-0.47, p<0.01), longer eating duration (r=0.53, p<0.01), and lower eating onset irregularity (r=-0.37, p<0.05). Later L5 correlated with later eating onset (r=0.67, p<0.001), offset (r=0.58, p<0.001), caloric midpoint (r=0.56, p<0.01), and greater eating offset irregularity (r=0.53, p<0.01). Later M10 correlated with later eating offset (r=0.40, p<0.05). Conclusion Preliminary findings indicate that eating timing and RAR are moderately correlated in free-living adults. Earlier eating timing, increased eating regularity, and longer daily eating duration may represent behavioral targets for improving circadian rhythms and subsequent cardiometabolic outcomes. Support (If Any): Support provided by the American Heart Association (#831488) and a University of Delaware Research Fund-Strategic Initiative Award.
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Malek, Zeina S., Dominique Sage, Paul Pévet, and Sylvie Raison. "Daily Rhythm of Tryptophan Hydroxylase-2 Messenger Ribonucleic Acid within Raphe Neurons Is Induced by Corticoid Daily Surge and Modulated by Enhanced Locomotor Activity." Endocrinology 148, no. 11 (November 1, 2007): 5165–72. http://dx.doi.org/10.1210/en.2007-0526.
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Tryptophan hydroxylase (TPH, the rate-limiting enzyme of serotonin synthesis) protein and mRNA levels display a circadian expression in the rat dorsal and median raphe. These patterns suggest a rhythmic synthesis of serotonin under the control of the master clock of suprachiasmatic nuclei. In the present study, we examined the involvement of endocrine and behavioral output signals of the master clock upon the Tph2 mRNA levels by quantitative in situ hybridization. In the absence of adrenals, a complete suppression of Tph2 mRNA rhythm was observed in dorsal and median raphe over 24 h. The restoration of corticosterone daily variations in adrenalectomized rats induced a Tph2 mRNA rhythmic pattern de novo, indicating that Tph2 mRNA rhythm is dependent upon daily fluctuations of glucocorticoids. Enhanced voluntary locomotor activity during 6 wk increased the level of Tph2 mRNA in both raphe nuclei of control rats without concomitant increase of corticosterone plasma levels. Moreover, this long-term enhanced locomotor activity was able to restore significant variation of Tph2 mRNA in adrenalectomized rats. In conclusion, both endocrine and behavioral cues can modulate Tph2 expression in dorsal and median raphe. The corticosterone surge acts as a rhythmic cue that induces the rhythmic expression of Tph2 in the raphe neurons. On the other hand, long-term exercise modulates the expression levels of this gene. Thus, the serotonin neurons are a target for both endocrine and behavioral circadian cues, and the serotoninergic input to the suprachiasmatic nuclei might feedback and influence the functioning of the clock itself.
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Levi, Francis, Sandra Komarzynski, Qi Huang, Teresa Young, Yeng Ang, Claire Fuller, Julia Brettschneider, et al. "Relevance of real-time teletransmission of physical activity, sleep, and circadian rhythms from gastrointestinal cancer (GIC) patients (pts) during daily routine (IDEAs, IRAS 233972)." Journal of Clinical Oncology 38, no. 4_suppl (February 1, 2020): 801. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.801.
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801 Background: The relative amount of activity and rest over the 24-hours, as measured by the dichotomy index I < O from actimetry records, is an independent predictor of overall survival and quality of life, and an early warning signal for emergency hospitalisation. The IDEAs study aimed to determine the sleep, physical and circadian pathologies in pts during their daily routine at home, which could lower I < O and be modifiable through personalised interventions. Methods: The rest-activity and surface temperature patterns were monitored in real time using a tele-transmitting chest sensor and a GPRS-platform for one week in 25 pts, with a WHO performance status of 0-1 and metastatic GIC (colorectal, 56%). Each pt completed questionnaires including Chronotype, HADS, and Pittsburgh Sleep Index, filled a precise diary of daily activities, meals and sleep times, and the MD Anderson Symptoms Inventory daily. I < O counts the In-bed activity bouts per min that are below the median activity Out-of-bed. Other pt-specific circadian parameters were estimated with spectral analyses and Hidden Markov models (HMM). I < O predictors were identified through correlation and regression analyses. Results: A poor I < O was found for 13 pts (52%). Self-reported scores for sleep quality or physical fitness showed no significant differences according to I < O. Yet HMM-modelled rest-activity revealed that pts with poor I < O had lower activity out-of-bed (median activity counts per minute, 110 vs 52, p = 0.001) and fractionated sleep (probability of remaining at rest when asleep, 94% vs 90%, p = 0.01). Poor I < O was significantly associated with an abnormal circadian rhythm in chest surface temperature, that was either wrongly timed or suppressed, for 83% of the pts as compared to 25% of those with a good I < O (p = 0.012). Conclusions: Nearly half of the pts displayed altered circadian rest-activity rhythm, with poor sleep and low daytime activity. In most of them, the circadian rhythm in body temperature, which critically regulates sleep, was abnormal. Exploration and specific treatment of sleep and circadian disorders are warranted for improving outcomes in cancer pts. Clinical trial information: 233972.
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Lévi, Francis, Sandra Komarzynski, Qi Huang, Teresa Young, Yeng Ang, Claire Fuller, Matei Bolborea, et al. "Tele-Monitoring of Cancer Patients’ Rhythms during Daily Life Identifies Actionable Determinants of Circadian and Sleep Disruption." Cancers 12, no. 7 (July 17, 2020): 1938. http://dx.doi.org/10.3390/cancers12071938.
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The dichotomy index (I < O), a quantitative estimate of the circadian regulation of daytime activity and sleep, predicted overall cancer survival and emergency hospitalization, supporting its integration in a mHealth platform. Modifiable causes of I < O deterioration below 97.5%—(I < O)low—were sought in 25 gastrointestinal cancer patients and 33 age- and sex-stratified controls. Rest-activity and temperature were tele-monitored with a wireless chest sensor, while daily activities, meals, and sleep were self-reported for one week. Salivary cortisol rhythm and dim light melatonin onset (DLMO) were determined. Circadian parameters were estimated using Hidden Markov modelling, and spectral analysis. Actionable predictors of (I < O)low were identified through correlation and regression analyses. Median compliance with protocol exceeded 95%. Circadian disruption—(I < O)low—was identified in 13 (52%) patients and four (12%) controls (p = 0.002). Cancer patients with (I < O)low had lower median activity counts, worse fragmented sleep, and an abnormal or no circadian temperature rhythm compared to patients with I < O exceeding 97.5%—(I < O)high—(p < 0.012). Six (I < O)low patients had newly-diagnosed sleep conditions. Altered circadian coordination of rest-activity and chest surface temperature, physical inactivity, and irregular sleep were identified as modifiable determinants of (I < O)low. Circadian rhythm and sleep tele-monitoring results support the design of specific interventions to improve outcomes within a patient-centered systems approach to health care.
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Saderi, Nadia, Adrián Báez-Ruiz, Lucia E. Azuara-Álvarez, Carolina Escobar, and Roberto C. Salgado-Delgado. "Differential Recovery Speed of Activity and Metabolic Rhythms in Rats After an Experimental Protocol of Shift-Work." Journal of Biological Rhythms 34, no. 2 (February 15, 2019): 154–66. http://dx.doi.org/10.1177/0748730419828534.
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The circadian system drives the temporal organization of body physiology in relation to the changing daily environment. Shift-work (SW) disrupts this temporal order and is associated with the loss of homeostasis and metabolic syndrome. In a rodent model of SW based on forced activity in the rest phase for 4 weeks, we describe the occurrence of circadian desynchrony, as well as metabolic and liver dysfunction. To provide better evidence for the impact of altered timing of activity, this study explored how long it takes to recover metabolic rhythms and behavior. Rats were submitted to experimental SW for 4 weeks and then were left to recover for one week. Daily locomotor activity, food intake patterns, serum glucose and triglycerides, and the expression levels of hepatic Pparα, Srebp-1c, Pepck, Bmal1 and Per2 were assessed during the recovery period and were compared with expected data according to a control condition. SW triggered the circadian desynchronization of all of the analyzed parameters. A difference in the time required for realignment was observed among parameters. Locomotor activity achieved the expected phase on day 2, whereas the nocturnal feeding pattern was restored on the sixth recovery day. Daily rhythms of plasma glucose and triglycerides and of Pparα, Pepck and Bmal1 expression in the liver resynchronized on the seventh day, whereas Srebp-1c and Per2 persisted arrhythmic for the entire recovery week. SW does not equally affect behavior and metabolic rhythms, leading to internal desynchrony during the recovery phase.
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Kim, Minjee, Kathryn Reid, Matthew Maas, Thanh-Huyen Vu, Rosemary Braun, Martha Daviglus, and Phyllis Zee. "164 Greater Light Exposure Is Associated with More Robust Rest-Activity Rhythms in Community-Dwelling Older Adults." Sleep 44, Supplement_2 (May 1, 2021): A67. http://dx.doi.org/10.1093/sleep/zsab072.163.
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Abstract Introduction Disrupted circadian rest-activity rhythms in older adults have been associated with an increased risk of cognitive decline and mortality. While light is one of the most potent synchronizing agents for the human circadian system, little is known about how light may influence rest-activity rhythms in older adults. We aimed to investigate the relationship between the amount of light exposure and rest-activity rhythm parameters using actigraphy data from a large cohort study. Methods 553 community-dwelling older adults (aged 72±5, 142 (25.5%) female) from the Chicago Healthy Aging Study cohort underwent recording of activity and ambient light exposure for a minimum of five 24-hour periods, using Actiwatch-L (Phillips Respironics). The average recording duration was 6.7±0.5 days. An extension to the traditional cosine model was used to compute circadian rest-activity rhythm parameters, including the amplitude (a measure of strength), the goodness of fit (pseudo F statistic; a measure of robustness), and acrophase (timing of peak activity). Light exposure was measured by time spent above light thresholds of 100, 200, 500, and 1000 lux per day (TAT100, TAT200, TAT500, TAT1000, respectively). Bivariate associations between rhythm parameters and TAT values were examined with Spearman’s correlation coefficients. Variables that met a significant threshold (p<0.05) were entered into multivariable models to adjust for potential confounders including age, sex, race, and season. Results Robustness of the rest-activity rhythm, measured by extended cosine pseudo-F statistics, was associated with TAT100 (partial Spearman’s correlation coefficient 0.12, p=0.008), TAT200 (coefficient 0.13, p=0.03), TAT500 (coefficient 0.16, p<0.001), and TAT 1000 (coefficient 0.18, p<0.001). TAT100/200/500/1000 were also associated with the strength of the rest-activity rhythm, measured by amplitude of the extended cosine fit (partial Spearman’s correlation coefficient vs. TAT100: 0.12, p=0.006, TAT200: 0.14, p=0.002, TAT500: 0.16, p<0.001, TAT1000: 0.18, p<0.001), after adjusting for age, sex, race, and season. Conclusion Across the seasons, greater daily light exposure is associated with more robust circadian rest-activity rhythm in community-dwelling older adults. Whether the enhancement of light exposure can improve the strength and robustness of rest-activity rhythm needs to be tested with future intervention studies. Support (if any):
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Yang, Hui-Wen, Sarah Chellappa, Arlen Gaba, Christian Cajochen, and Kun Hu. "758 Circadian rest-activity signatures in women with major depressive disorder." Sleep 44, Supplement_2 (May 1, 2021): A295—A296. http://dx.doi.org/10.1093/sleep/zsab072.755.
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Abstract Introduction Patients with major depressive disorder (MDD) show disrupted circadian rhythms and sleep, including reduced daytime physical activity and poor sleep quality. However, previous findings are masked by psychotropic medication intake, co-morbid diseases and years of chronic mental illness. Here, we aim at identifying circadian motor activity patterns in unmedicated women at the onset of MDD. Methods Twelve young unmedicated women with MDD (Mean+-SD: 24.9+-5.2y; range: 18-33y) and eight age-matched healthy women (Mean+-SD: 24.5+-3.2y; range: 20-31y) participated in our study. Activity recordings were collected using wrist-worn wearable devices (actigraphs) for ~7 days in real-life settings. Cosinor analyses were performed to assess the amplitude and phase of the 24-h rest-activity activity rhythms. Non-parametric analyses were used to quantify interdaily stability and intradaily variability of the rest-activity rhythm. Furthermore, we calculated the mean activity level and scaling exponent alpha, which quantifies the temporal correlation in activity fluctuations, per 3-h bins across the 24-h sleep-wake cycle. Results Women with MDD showed a significantly higher amplitude of the 24-h rest-activity activity rhythm (Mean+-SD: 332.7+-120.8 arbitrary units) than the controls (179.7+-122.9; p=0.002), elicited by higher activity levels during the daytime (0-12h after habitual wake-up time; p<0.01). In contrast, women with MDD showed a trend for lower interdaily stability levels than controls (respectively, 0.41+-0.07 and 0.46+-0.08; p=0.05). Interestingly, a significant interaction effect of “group” and “time since habitual wake” was elicited for scaling exponent alpha (p<0.001). Accordingly, women with MDD had higher alpha values during habitual sleep (0–6 hours before habitual wake-up time) than controls (respectively, 1.18+-0.22 and 1.12+-0.22). Conclusion Unmedicated women at the onset of MDD had altered circadian motor activity patterns, as indexed by higher amplitude particularly during daytime while awake, less stable 24-h activity rhythms, and highly correlated activity patterns during sleep that closely resemble those typically occurring during wakefulness. These findings suggest that MDD per se may be associated with impaired rest-activity profiles. Ultimately, the use of wearable devices might hold important prospects for the early detection of individuals at risk for mood disorders. Support (if any) Swiss National Science Foundation Grants START #3100–055385.98, 3130-0544991.98 and 320000-108108; NIH RF1AG064312, RF1AG059867
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Kleckner, Amber, Jennifer E. Reschke, Brian James Altman, Elizabeth Belcher, Richard Francis Dunne, Fergal J. Fleming, Nikesha Gilmore, et al. "A 10-hour time-restricted eating intervention to address cancer-related fatigue among cancer survivors." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 12109. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.12109.
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12109 Background: Cancer-related fatigue is a common, debilitating condition that can persist for months or years after cancer treatment. Time-restricted eating has been shown to improve circadian rhythm and strengthen rest and activity patterns, and therefore could help reduce persistent fatigue. Herein, we evaluated the feasibility of recruiting cancer survivors to a two-week, single-arm, time-restricted eating intervention with a 10-h eating window, assessed safety of the intervention, monitored adherence, and obtained initial estimates of within-group change in patient-reported fatigue. Methods: We recruited adults 4-60 months post-cancer treatment who had a fatigue level ≥3 on a scale from 0-10 and who did not already consume food within a 10-h window. Participants were asked to consume all food and beverages within a self-selected 10-h eating window for 14 days; water was allowed at all times. Participants completed a daily diary indicating when they began and stopped eating each day. To assess fatigue, participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Brief Fatigue Inventory (BFI) at pre- and post-intervention. We report mean±standard deviation and used a t-test to assess differences in pre- vs. post-intervention scores. Results: A total of 21 participants consented (20 breast cancer, 1 prostate cancer; 20 female; age 57.7±11.4 years; 1.6±1.1 years post-primary treatment). The study was feasible: 19/21 (90.5%) completed pre- and post-intervention assessments and daily diaries. It was also safe: there were two mild adverse events—one unlikely (insomnia) and one possibly related to the intervention (acute headache) and no severe adverse events. Most of the participants adhered to the intervention; 14/19 (73.7%) ate all of their food within a 10-h window at least 80% of the days, and 16/19 (84.2%) reported an average eating window ≤10 h. Fatigue scores improved a clinically meaningful degree for FACIT-F total score, FACIT-F fatigue subscale, and the BFI total score from pre- to post-intervention per established cutoffs (Table). Conclusions: Cancer survivors were willing and able to adhere to a two-week time-restricted eating intervention, and the intervention was safe. Also, fatigue was reduced with moderate to large effect sizes after two weeks of time-restricted eating. Based on our results, a follow-up randomized controlled trial to investigate time-restricted eating to alleviate cancer-related fatigue among cancer survivors is indicated. Funding: NIH/NCI UG1CA189961, T32CA102618. Clinical trial information: NCT04243512. [Table: see text]
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Bertolucci, Cristiano, Anna Borroni, and Anna Loy. "Daily and circadian rhythms of rest and activity ofTalpa romana Thomas (Mammalia, Insectivora: Talpidae). Preliminary results." Rendiconti Lincei 10, no. 2 (June 1999): 89–99. http://dx.doi.org/10.1007/bf02904384.
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Kolberg, Eirin, Ståle Pallesen, Gunnhild Johnsen Hjetland, Inger Hilde Nordhus, and Elisabeth Flo-Groeneboom. "The Effect of Bright Light Treatment on Rest–Activity Rhythms in People with Dementia: A 24-Week Cluster Randomized Controlled Trial." Clocks & Sleep 3, no. 3 (September 13, 2021): 449–64. http://dx.doi.org/10.3390/clockssleep3030032.
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Bright light treatment is an effective way to influence circadian rhythms in healthy adults, but previous research with dementia patients has yielded mixed results. The present study presents a primary outcome of the DEM.LIGHT trial, a 24-week randomized controlled trial conducted at nursing homes in Bergen, Norway, investigating the effects of a bright light intervention. The intervention consisted of ceiling-mounted LED panels providing varying illuminance and correlated color temperature throughout the day, with a peak of 1000 lx, 6000 K between 10 a.m. and 3 p.m. Activity was recorded using actigraphs at baseline and after 8, 16, and 24 weeks. Non-parametric indicators and extended cosine models were used to investigate rest–activity rhythms, and outcomes were analyzed with multi-level regression models. Sixty-one patients with severe dementia (median MMSE = 4) were included. After 16 weeks, the acrophase was advanced from baseline in the intervention group compared to the control group (B = −1.02, 95%; CI = −2.00, −0.05). There was no significant difference between the groups on any other rest–activity measures. When comparing parametric and non-parametric indicators of rest–activity rhythms, 25 out of 35 comparisons were significantly correlated. The present results indicate that ambient bright light treatment did not improve rest–activity rhythms for people with dementia.
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Stahl, Sarah. "DIGITAL MONITORING OF SLEEP, MEALS, AND EXERCISE AS A PREVENTIVE INTERVENTION FOR DEPRESSION IN BEREAVED SPOUSES." Innovation in Aging 3, Supplement_1 (November 2019): S604. http://dx.doi.org/10.1093/geroni/igz038.2249.
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Abstract The death of a spouse brings profound change to bereaved survivors’ lifestyle and daily routine. These changes disrupt circadian rhythms which, in turn, places individuals at high risk for depression. The purpose of this study is to examine the feasibility and acceptability of a 12-week behavioral intervention that targets the timing and regularity of sleep, meals, and physical activity via digital monitoring and motivational health coaching. Participants were 60+ years of age and assessed on intervention acceptability and adherence, depression symptoms (Hamilton Rating Scale for Depression) and the rest-activity rhythm, (a downstream indicator of the body’s circadian rhythm (via actigraphic technology). The intervention was rated highly by participants (n=55); 88% were compliant in digital monitoring and 95% were retained. Depression symptoms declined from pre-to post-intervention; and the regularity of circadian rhythms increased. An intervention that targets the regularity of day- and nighttime activities may reduce depression in older spousally-bereaved adults.
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Chaix, Amandine, Emily N. C. Manoogian, Girish C. Melkani, and Satchidananda Panda. "Time-Restricted Eating to Prevent and Manage Chronic Metabolic Diseases." Annual Review of Nutrition 39, no. 1 (August 21, 2019): 291–315. http://dx.doi.org/10.1146/annurev-nutr-082018-124320.
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Molecular clocks are present in almost every cell to anticipate daily recurring and predictable changes, such as rhythmic nutrient availability, and to adapt cellular functions accordingly. At the same time, nutrient-sensing pathways can respond to acute nutrient imbalance and modulate and orient metabolism so cells can adapt optimally to a declining or increasing availability of nutrients. Organismal circadian rhythms are coordinated by behavioral rhythms such as activity–rest and feeding–fasting cycles to temporally orchestrate a sequence of physiological processes to optimize metabolism. Basic research in circadian rhythms has largely focused on the functioning of the self-sustaining molecular circadian oscillator, while research in nutrition science has yielded insights into physiological responses to caloric deprivation or to specific macronutrients. Integration of these two fields into actionable new concepts in the timing of food intake has led to the emerging practice of time-restricted eating. In this paradigm, daily caloric intake is restricted to a consistent window of 8–12 h. This paradigm has pervasive benefits on multiple organ systems.
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Roecklein, K. A., D. L. Wescott, S. F. Smagula, A. M. Soehner, P. L. Franzen, and B. P. Hasler. "0037 Melanopsin Driven Pupil Responses and Physical Activity: Stability of Activity from Day-to-Day in Winter in Seasonal Affective Disorder." Sleep 43, Supplement_1 (April 2020): A15. http://dx.doi.org/10.1093/sleep/zsaa056.036.
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Abstract Introduction The post-illumination pupil response (PIPR) is a measure of the responsivity of intrinsically photosensitive retinal ganglion cells (ipRGCs), and reflects the cell biology of the photoentrainment pathway projecting from the retina to the circadian clock. Adequate signaling from the ipRGCs in the retina to the circadian clock is necessary to result in robust circadian output which we hypothesize would increase inter-daily stability (IS), a non-parametric modeling technique that examines stability of rest activity rhythms across successive days. Methods Participants were aged 18–66 years and recruited from the greater Pittsburgh area during the Winter with Seasonal Affective Disorder who completed both actigraphy and pupillometry (n = 16). PIPR measures were collected after a 1 second red or blue light pulse, and are calculated as the Net difference between red and blue at multiple time frames: at 6 seconds post stimulus (PIPR 6), from 10–30 seconds post-stimulus (PIPR 20), or from 10–40 seconds post-stimulus (PIPR 30). Using actigraphy, inter-daily stability (IS) was calculated as the amount of overall variability in the recording that is accounted for by the typical 24-hour profile, and reflects stability of the mean 24-h profile day-to-day. Results Inter-daily stability (IS) was associated with Net PIPR 20 (Β = 0.561; p = .031) and Net PIPR 30 (Β = 0.551; p = .034; all Β’s are standardized), but not Net PIPR 6 (Β = 0.298; p = .304). Retinal irradiance was calculated for each participant based on age and pupil diameter, to account for age-related differences in transmission of the stimulus to the retina. All raw Net PIPR values were adjusted for calculated retinal irradiance, and gender and time since wake were included as covariates. Conclusion Inter-daily stability (IS) values indicate greater stability of 24-hour activity profiles across days. If reduced responsivity to entraining pulses of light is associated with day-to-day instability in activity rhythms, as shown here, we might expect that amplifying entraining light through environmental changes or bright light therapy would normalize inter-daily stability in SAD, or the reverse, stabilizing activity profiles across days could improve depression and/or normalize retinal ipRGC responsivity. Support NIMH K.A.R. MH103303
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Graham, Jessica L., Katie B. Needham, Emily M. Bertucci, Alexis A. Pearson, Carolyn M. Bauer, and Timothy J. Greives. "Onset of Daily Activity in a Female Songbird Is Related to Peak-Induced Estradiol Levels." Integrative and Comparative Biology 59, no. 4 (June 24, 2019): 1059–67. http://dx.doi.org/10.1093/icb/icz112.
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Abstract Research in captive birds and mammals has demonstrated that circadian (i.e., daily) behavioral rhythms are altered in response to increases in sex-steroid hormones. Recently, we and others have demonstrated a high degree of individual repeatability in peak (gonadotropin-releasing hormone [GnRH]-induced sex) steroid levels, and we have found that these GnRH-induced levels are highly correlated with their daily (night-time) endogenous peak. Whether or not individual variation in organization and activity of the reproductive endocrine axis is related to daily timing in wild animals is not well known. To begin to explore these possible links, we tested the hypothesis that maximal levels of the sex steroid hormone estradiol (E2) and onset of daily activity are related in a female songbird, the dark-eyed junco (Junco hyemalis). We found that females with higher levels of GnRH-induced E2 departed from their nest in the morning significantly earlier than females with lower stimulated levels. We did not observe a relationship between testosterone and this measure of onset of activity. Our findings suggest an interaction between an individual’s reproductive endocrine axis and the circadian system and variation observed in an individuals’ daily activity onset. We suggest future studies examine the relationship between maximal sex-steroid hormones and timing of daily activity onset.