Normal Circadian Rhythm Research Articles

P067 How much sleep medicine is taught to Australian and New Zealand medical students?

Abstract Background Sleep disorders are prevalent with wide-ranging consequences but often underdiagnosed. Previous research indicates low coverage of sleep topics in medical curricula and knowledge gaps in primary care physicians around the world. Methods The medical dean and one staff member from the 22 medical programs in Australia and New Zealand were surveyed about sleep content within the curriculum and barriers and facilitators to providing sleep education. Results Eleven programs responded (48% responding; 5 undergraduate-, 4 postgraduate-entry, 2 both) and reported a median of 4h of sleep education (IQR 1.0 – 5.9h). Most frequently covered topics were normal sleep (91% of respondents), sleep apnoea (91%), insomnia (55%), circadian disorders (51%), sleep and circadian rhythms as related to student wellbeing (45%), movement disorders (36%), hypersomnias (36%), and parasomnias (27%). More than half gave students the opportunity to meet a sleep specialist (55%), but fewer provided opportunities to attend a sleep clinic (36%), observe a sleep investigation (27%), or visit a sleep laboratory (18%). Most respondents (73%) believed sleep content could be increased; these institutions actually provided more sleep education than their counterparts (median 7.4h vs. 3.3h). Respondents suggested professional bodies can help by advising on educational frameworks, developing standard learning outcomes, and creating reference and teaching materials but noted the main barrier of limited space in the curriculum. Conclusions There is scope to improve sleep education in Australian and New Zealand medical programs, however, consensus on core topics and content integration with other disciplines are key, given limited curriculum space and time.

Night shift-induced circadian disruption: links to initiation of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and risk of hepatic cancer.

The circadian system plays a crucial role in regulating metabolic homeostasis at both systemic and tissue levels by synchronizing the central and peripheral clocks with exogenous time cues, known as zeitgebers (such as the light/dark cycle). Our body's behavioral rhythms, including sleep-wake cycles and feeding-fasting patterns, align with these extrinsic time cues. The body cannot effectively rest and repair itself when circadian rhythms are frequently disrupted. In many shift workers, the internal rhythms fail to fully synchronize with the end and start times of their shifts. Additionally, exposure to artificial light at night (LAN), irregular eating patterns, and sleep deprivation contribute to circadian disruption and misalignment. Shift work and jet lag disrupt the normal circadian rhythm of liver activity, resulting in a condition known as "circadian disruption". This disturbance adversely affects the metabolism and homeostasis of the liver, contributing to excessive fat accumulation and abnormal liver function. Additionally, extended working hours, such as prolonged night shifts, may worsen the progression of non-alcoholic fatty liver disease (NAFLD) toward non-alcoholic steatohepatitis (NASH) and increase disease severity. Studies have demonstrated a positive correlation between night shift work (NSW) and elevated liver enzymes, indicative of hepatic metabolic dysfunction, potentially increasing the risk of hepatocellular carcinoma (HCC) related to NAFLD. This review consolidates research findings on circadian disruption caused by NSW, late chronotype, jet lag, and social jet lag, drawing insights from studies involving both humans and animal models that investigate the effects of these factors on circadian rhythms in liver metabolism.

Light, sleep and circadian rhythm in critical illness.

Sleep and circadian disruption (SCD) are associated with worse outcomes in the ICU population. We discuss sleep, circadian physiology, the role of light in circadian entrainment and its possible role in treating SCD, with special attention to the use of light therapies and ICU design. The American Thoracic Society recently published an official research statement highlighting key areas required to define and treat ICU SCD. Recent literature has been predominantly observational, describing how both critical illness and the ICU environment might impair normal sleep and impact circadian rhythm. Emerging consensus guidance outlines the need for standardized light metrics in clinical trials investigating effects of light therapies. A recent proof-of-concept randomized controlled trial (RCT) showed improvement in delirium incidence and circadian alignment from ICU room redesign that included a dynamic lighting system (DLS). Further investigation is needed to define the optimal physical properties of light therapy in the ICU environment as well as timing and duration of light treatments. Work in this area will inform future circadian-promoting design, as well as multicomponent nonpharmacological protocols, to mitigate ICU SCD with the objective of improving patient outcomes.

Impact of cadmium and diclofenac exposure on biochemical responses, transcriptome, gut microflora, and growth performance in grass carp (Ctenopharyngodonidella)

In recent years, the concentrations of cadmium (Cd) and diclofenac (DCF) in water have frequently exceeded the standard; however, the toxic effects of these two pollutants on grass carp under single and combined exposure are unknown. In this study, the concentrations of pollutants in different tissues were detected, and the toxicities of the two pollutants to grass carp under different exposure conditions were compared based on growth traits, biochemical responses, gut microbiome, and transcriptomes. Based on these findings, the brain showed the lowest levels of Cd and DCF accumulation. Oxidative stress and pathological damage were observed in the brain and intestines. Changes in the structure and abundance of the gut microflora affect the synthesis of neurotransmitters, such as GABA and steroids. Differentially expressed genes in the brain were enriched in circadian rhythm functions. The expression of PER, CLOCK,1L-1β, 1L-17, and other genes are related to the abundance of Akkermansia, which indicates that the disorder of gut microflora will affect the normal circadian rhythm of the brain. All indices in the recovery group showed an increasing trend. Overall, the toxicity of Cd and DCF showed antagonism, and a single exposure had a stronger effect on gut microorganisms and circadian rhythm, which provided a scientific basis for exploring the comprehensive effects of different pollutants.

Mice Mutated in the First Fibronectin Domain of Adhesion Molecule L1 Show Brain Malformations and Behavioral Abnormalities.

The X-chromosome-linked cell adhesion molecule L1 (L1CAM), a glycoprotein mainly expressed by neurons in the central and peripheral nervous systems, has been implicated in many neural processes, including neuronal migration and survival, neuritogenesis, synapse formation, synaptic plasticity and regeneration. L1 consists of extracellular, transmembrane and cytoplasmic domains. Proteolytic cleavage of L1's extracellular and transmembrane domains by different proteases generates several L1 fragments with different functions. We found that myelin basic protein (MBP) cleaves L1's extracellular domain, leading to enhanced neuritogenesis and neuronal survival in vitro. To investigate in vivo the importance of the MBP-generated 70 kDa fragment (L1-70), we generated mice with an arginine to alanine substitution at position 687 (L1/687), thereby disrupting L1's MBP cleavage site and obliterating L1-70. Young adult L1/687 males showed normal anxiety and circadian rhythm activities but enhanced locomotion, while females showed altered social interactions. Older L1/687 males were impaired in motor coordination. Furthermore, L1/687 male and female mice had a larger hippocampus, with more neurons in the dentate gyrus and more proliferating cells in the subgranular layer, while the thickness of the corpus callosum and the size of lateral ventricles were normal. In summary, subtle mutant morphological changes result in subtle behavioral changes.

How Light Affects Circadian Rhythm and Mood Regulation

Light is full of the world and illuminates our lives, and scientists believe that light must play a crucial role in affecting humans either positively or negatively including circadian functions and emotion-related behaviors. Through experiments, researchers have revealed the fact that light can affect humans significantly and the principles behind phenomena of light influencing humans both physically and mentally. This essay focuses on how light works in humans’ circadian rhythm and mood regulation, and how exactly nocturnal light exposure induces depression-like behaviors. Many research results indicate that natural light can help reset circadian rhythm of humans when the normal circadian rhythm is disturbed by trans meridian travel or working during night. Thus, scientific time of light exposure helps to relieve jet-lag symptoms and allows people to have a healthier mental and physical state. Studies by Fernandez D C et al. and An K. et al. are included in this essay to demonstrate the effects of light on mood. Fernandez D C et al. experimentally confirm that PHb (perihabenular nucleus) is necessary in the circuit of light affecting mood through ipRGC which is the only receptor of light input to influence circadian functions of the brain. Subsequently, An K. et al. conducted a series of experiments on mice to investigate the role of a subcortical pathway regulated by circadian rhythms in modulating mood-related behaviors resulted from nighttime light exposure in mice. The findings provide insights into the mechanisms underlying the impact of nocturnal light on mood regulation and highlight the importance of considering circadian rhythms in understanding the effects of environmental factors on mental health. Overall, these studies allow more scientists to think about how to employ light as therapy as well as development of new anti-depressants based on the research of the ipRGC circuit.

Abstract 5517: Chronic stress causes metastasis via neutrophil-mediated changes to the microenvironment

Abstract Chronic stress is associated with increased risk of metastasis and poor survival in cancer patients, yet the reasons are unclear. We show that chronic stress increased lung metastasis from disseminated cancer cells 2- to 4-fold in mice. Chronic stress significantly altered the lung microenvironment, with fibronectin accumulation, reduced T cell infiltration, and increased neutrophil infiltration. Depleting neutrophils abolished stress-induced metastasis, indicating their critical role. Chronic stress shifted neutrophils’ normal circadian rhythm, and, via glucocorticoid release, caused increased neutrophil extracellular trap (NET) formation. Importantly, in mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress failed to increase NETs and metastasis. Furthermore, digesting NETs with deoxyribonuclease (DNase) I prevented chronic stress-induced metastasis. Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, NETs could be targets for preventing metastatic recurrence in cancer patients, many of whom will experience chronic stress due to their disease. Citation Format: Xue-Yan He, Yuan Gao, David Ng, Evdokia Michalopoulou, Shanu George, Jose M. Adrover, Lijuan Sun, Jean Albrengues, Juliane Daßler-Plenker, Xiao Han, Ledong Wan, Xiaoli S. Wu, Longling S. Shui, Yu-Han Huang, Bodu Liu, Chang Su, David L. Spector, Christopher R. Vakoc, Linda VanAelst, Mikala Egeblad. Chronic stress causes metastasis via neutrophil-mediated changes to the microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5517.

Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment

Chronic stress is associated with increased risk of metastasis and poor survival in cancer patients, yet the reasons are unclear. We show that chronic stress increases lung metastasis from disseminated cancer cells 2- to 4-fold in mice. Chronic stress significantly alters the lung microenvironment, with fibronectin accumulation, reduced Tcell infiltration, and increased neutrophil infiltration. Depleting neutrophils abolishes stress-induced metastasis. Chronic stress shifts normal circadian rhythm of neutrophils and causes increased neutrophil extracellular trap (NET) formation via glucocorticoid release. In mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress fails to increase NETs and metastasis. Furthermore, digesting NETs with DNase I prevents chronic stress-induced metastasis. Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, NETs could be targets for preventing metastatic recurrence in cancer patients, many of whom will experience chronic stress due to their disease.

Effects of melatonin on the management of multiple sclerosis: A scoping review on animal studies

<abstract><sec> <title>Background</title> <p>Multiple sclerosis (MS), is a debilitating neurological disease that currently has various treatments, like disease-modifying therapies, monoclonal antibodies, corticosteroids, and hormonal derivatives. Melatonin has several actions, like regulating circadian rhythms, which are usually used for insomnia. This scoping review aimed to explore the efficacy of melatonin, both as a standalone treatment and in conjunction with other drugs, in the management of MS in animal models.</p> </sec><sec> <title>Methods</title> <p>We searched PubMed, Web of Science, EMBASE, and Google Scholar using (“melatonin” OR “melatonin receptor”) AND (“multiple sclerosis”) AND (“animal”). Animal studies that evaluated the effects of melatonin on the development, progression, and outcomes of MS were included. Human studies and other types of studies like case reports were excluded. We used narrative synthesis for reporting the results.</p> </sec><sec> <title>Results</title> <p>Overall, 21 studies were included, conducted on mice (n = 15) and rats (n = 6). Mostly, studies reported that melatonin led to normal circadian rhythms in animals. Melatonin in doses of both 50 and 100 mg/kg were useful in nociception latency. Melatonin in combination with other drugs like H-89, diisopropylamine dichloroacetate, gibberellins, and IFN-1β improved outcomes, while there was not improved cognition in combination with mesenchymal stem cells. In some tests, male subjects showed significantly better responses. There were controversial results regarding the effects of melatonin on cytokines, but overall, it led to a reduction in proinflammatory cytokines.</p> </sec><sec> <title>Conclusions</title> <p>Melatonin overall demonstrated favorable outcomes regarding oxidative stress, anti-inflammation, and cytokine levels across various doses. It is recommended conducting systematic reviews and meta-analyses with a larger number of primary studies to provide more comprehensive insights.</p> </sec></abstract>

Circadian rhythms in the Drosophila eye may regulate adaptation of vision to light intensity.

The sensitivity of the eye at night would lead to complete saturation of the eye during the day. Therefore, the sensitivity of the eye must be down-regulated during the day to maintain visual acuity. In the Drosophila eye, the opening of TRP and TRPL channels leads to an influx of Ca++ that triggers down-regulation of further responses to light, including the movement of the TRPL channel and Gα proteins out of signaling complexes found in actin-mediated microvillar extensions of the photoreceptor cells (the rhabdomere). The eye also exhibits a light entrained-circadian rhythm, and we have recently observed that one component of this rhythm (BDBT) becomes undetectable by antibodies after exposure to light even though immunoblot analyses still detect it in the eye. BDBT is necessary for normal circadian rhythms, and in several circadian and visual mutants this eye-specific oscillation of detection is lost. Many phototransduction signaling proteins (e.g., Rhodopsin, TRP channels and Gα) also become undetectable shortly after light exposure, most likely due to a light-induced compaction of the rhabdomeric microvilli. The circadian protein BDBT might be involved in light-induced changes in the rhabdomere, and if so this could indicate that circadian clocks contribute to the daily adaptations of the eye to light. Likewise, circadian oscillations of clock proteins are observed in photoreceptors of the mammalian eye and produce a circadian oscillation in the ERG. Disruption of circadian rhythms in the eyes of mammals causes neurodegeneration in the eye, demonstrating the importance of the rhythms for normal eye function.

NANDA taxonomy and insomnia evaluation scale in older people: A crosssectional study

Objective: To identify the prevalence of indicators of the nursing diagnosis “insomnia” in older people through the Insomnia Severity Index (ISI) scale. Materials and methods: Cross-sectional epidemiological study involving older individuals from a community center. Data analysis was conducted between July and August 2021 using the R program. Univariate analysis was adopted for sociodemographic characterization. The χ² test (Pearson’s chi-square) was employed to assess the association between the sociodemographic variables, nursing diagnosis indicators, and the ISI. Results: A total of 90 older people (mean age = 76.8 years, SD = 7.2 years) with at least one defining characteristic were included in this study. There was a higher prevalence of the diagnostic indicators “insufficient physical endurance” (75.6%; 95% CI: 65-83%) and “average daily physical activityis less than recommended for age and gender” (71.1%; 95% CI: 61-79%). In contrast, the diagnostic indicators “increased accidents” (6.7%; 95% CI: 3-13%) and “lifestyle incongruent with normal circadian rhythms” (2.2%; 95% CI: 92-99%) had a lower prevalence. A significant association was found between ISI, the defining characteristics (p = 0.009; < 0.001; 0.005; 0.002; 0.022; < 0.001; 0.004; < 0.001), and the related factors (p = 0.007; 0.004; < 0.001; 0.006; 0.049) of nursing diagnosis. Conclusions: The prevailing indicators of insomnia in community-dwelling older individuals were demonstrated in our sample and their association with a validated clinical assessment survey was established. These findings may contribute to nurses’ diagnostic accuracy and their abilityto conduct effective diagnostic screening in older populations.

Are there differences in the adaptive profile of hair sheep and their crosses with wool breeds?

This study aimed to evaluate and compare the physiological performance of different genetic groups of sheep, by physiological variables and serum hormone levels, in a hot weather environment. Thirty sheep from five genetic groups were used: Santa Inês (SI), ½ Dorper + ½ Santa Inês (DO), ½ Ilê de France + ½ Santa Inês (IF), ½ Suffolk + ½ Santa Inês (SK), and ½ Texel + ½ Santa Inês (TX). The readings and records of physiological parameters (respiratory rate (RR), rectal temperature (RT), auricular cavity temperature (ACT), and surface temperature (ST)) were carried out at 7:00 am, 1:00pm, and 7:00pm, in 12 non-consecutive days. The collections of blood samples for hormone analysis (triiodothyronine (T3), thyroxine (T4), and cortisol (CORT)) is in four consecutive days. The environmental conditions of the experimental period caused a thermal discomfort in the sheep, but not a state of thermal stress. The thermolysis mechanisms, sensitive (ST and ACT) and latent (RR) processes, were enough to maintain their homeostasis (RT). The results showed that crossbred breeds presented a higher metabolism and were more efficient at dissipating heat through thermolysis than the SI breed. The crossbred breeds were efficient at dissipating heat through the elevation of body surface temperature and respiratory rate, mainly SK and TX, i.e., crossbred breeds, despite the wool cover, used thermoregulatory mechanisms that promoted lower variation of RT. The analysis of variance showed significant effects (P < 0.05) to the time factor in the responses of T4 and T3, and to the breed factor in the responses of CORT, T4, and T3. We did not observe interaction between the factors to any of the hormonal variables. Therefore, we can state that the effect of time was independent of breed and vice versa. Thyroid hormones presented lower blood concentration in the mornings (4.03 ± 0.82, T4; 65.08 ± 10.6, T3), increasing their concentration in the afternoon (4.60 ± 1.03, T4; 70.16 ± 14.17, T3). The thyroid hormones presented a normal circadian rhythm, with the exception of SK. Air temperature (AT) showed greater correlation with physiological variables than enthalpy (H) did, in the experimental conditions. However, H showed correlation with T4 and T3. The adaptive profile of the genetic groups under study are different, but the IF genetic group showed better performance under environmental conditions.

Fatigue risk assessment of a Helicopter Emergency Medical Service crew working a 24/7 shift pattern: results of a prospective service evaluation

BackgroundThe work of Helicopter Emergency Medical Services (HEMS) teams crosses the boundaries of several high-risk occupations including medicine, aviation, and transport. Working conditions can be challenging and operational demands requires a 24-h rota, resulting in disruption of the normal circadian rhythm. HEMS crews are therefore prone to both mental and physical fatigue. As fatigue in medical providers is linked to poor cognitive performance, degradation of psychomotor skills and error, this study aimed to explore the existence of predictable patterns of crew-fatigue in a HEMS service.MethodsHEMS medical crew members working a 3-on 3-off forward rotating rota with a 5-week shift cycle were asked to do psychomotor vigilance tests (PVT) as an objective measure of fatigue. PVT testing was undertaken at the start, mid- and at the end of every shift during a full 5-week shift cycle. In addition, they were asked to score subjective tiredness with the Samn-Perelli Fatigue Scale (SPFS), and to keep a Transport Fatigue Assessment shift log, wherein they noted shift characteristics potentially related to fatigue. Primary outcome of interest was defined as the change in PVT and SPFS scores over time.ResultsMean baseline resting PVT in milliseconds at the start of the study period was 427 [390–464]. There was an overall trend towards higher PVT-scores with shift progression mean [95% CI] PVT at the start of shifts 447 [433–460]; halfway through the shift 452 [440–463]; end of the shift 459 [444–475], p = 0.10), whereas SPFS scores remained constant. Within a 5 week forward-rotating cycle, an overall trend towards a gradual increase in both average PVT (from 436 [238–454] to 460 [371–527, p = 0.68] ms;) and SPFS (from 2.9 [2.6–3.2] to 3.6 [3.1–4.0], p = 0.38) was observed, although significant interindividual variation was present. Reported SPFS scores ≥ 4 (moderate fatigue) were mainly related to workload (number of jobs) and transport mode (car-based shifts).ConclusionAn overall trend towards a decline in psychomotor vigilance and an increase in self-reported tiredness was found for HEMS crew over a 5-week shift cycle. Using a bespoke predictive fatigue tool on a day-to-day basis could increase fatigue awareness and provide a framework to which relevant mitigating options can be applied.

Clinical Significance of Nocturnal Hypertension and Nighttime Blood Pressure Dipping in Hypertension.

This narrative review article aims to discuss more recent evidence, current challenges, and future perspectives regarding the clinical importance of nocturnal hypertension and nighttime blood pressure dipping, with particular reference to diagnosis, prognostic value, and therapeutic approach. The importance of nighttime blood pressure and nighttime blood pressure dipping has been demonstrated in decades. Increased nighttime blood pressure has been acknowledged as an unfavorable clinical trait. However, more recent evidence suggests that the abolishment of normal circadian blood pressure rhythm is not always a solid predictor of adverse cardiovascular events and needs to be interpreted in the light of each patients' individual characteristics. Physicians treating hypertensive patients with adverse nighttime blood pressure profiles often face the dilemma of chronotherapy. This has been a blurred field for years, yet very recent evidence from appropriately designed studies attempts to shed light on this puzzling question. As 24-h ambulatory blood pressure monitoring is being increasingly recommended and applied in real-world practice for the diagnosis and monitoring of hypertension, information on nighttime blood pressure and nocturnal dipping profile is collected but is not always easy to interpret.

O033 Is Sleeping and Waking Important for the Cortisol Awakening Response?

Abstract Introduction The rapid rise in cortisol after waking is known as the cortisol awakening response (CAR). However, as part of its normal circadian rhythm cortisol also rises in the morning independent of awakening. If CAR is a direct response to awakening, it should be eliminated in conditions of sleep deprivation (SD). Given that an atypical CAR is associated with several psychiatric and medical disorders, understanding the factors that influence CAR is of clinical relevance. This study explored cortisol during the normal waking period prior, during, and post-SD. Methods N=21 (11F 22.80±4.40y) completed 62h of SD in the laboratory. Salivary cortisol was collected across 5-time-points (07:00h, 07:15h, 07:30h, and 07:45h) on 2-pre-at-home-study days, 4-in-lab-study days, and 2-post-at-home-study days. Mixed-effects ANOVAs tested for fixed effects of day, time, and their interactions on cortisol, and cortisol area under the curve (AUCi, AUCg). Results SD produced significant effects of time*day (p&amp;lt;0.001). Cortisol levels at +30 and +45min post-awakening were lower on SD days. Cortisol levels on awakening (0mins) did not differ between any study days. There were significant effects of day (p&amp;lt;0.001). AUCi and AUCg were greater on in-laboratory-baseline and recovery days compared to other study days. Discussion This study found CAR is not present during periods of SD when there is no ‘waking’ from sleep. It showed for the first time that CAR recovers to baseline levels following recovery sleep. While the role of the CAR remains unclear this study identified factors that future research should consider to advance understanding of its purpose.

ULTRASTRUCTURAL CHANGES OF THE PINEAL GLAND IN EPILEPSY

Circadian mechanisms modulate neuronal excitability at several levels, and their destruction can cause excessive uncontrolled excitability. Previous studies have shown that epilepsy is associated with melatonin levels. Melatonin is a powerful chronobiotic secreted from the pineal gland; helps to maintain normal circadian rhythms and is used to treat some neurological and psychiatric disorders. Circadian rhythms and sleep/wake mechanisms play role in the epilepsy. Melatonin deficiency can decrease seizure threshold, and hence could increase seizure activity. The aim of the study was to identify ultrastructural changes in the pineal gland in an experimental model of epilepsy. Materials and methods. The experiment was carried out on Wistar rats, 5-6 months of age, weight of about 200 g, 36 experimental and 10 control animals. Electrically provoked experimental epileptic seizures model in rats was reproduced. The rats developed spontaneous generalized seizures after 9-14 stimulations. Material for histological examinations was taken after stable formation (for &gt;1 month) of repeated seizures. Ultrathin sections, after contrast with Reynolds lead citrate, were studied under an electron microscope at an accelerating voltage of 75 kV. The increase was selected adequate to the study and ranged from 20,000 to 60,000 times. Results. Experimental studies have confirmed the presence of stable dystrophic, up to apoptosis of some cells, morphological changes of the pineal gland in the experimental model of epilepsy in rats, which is the reason for the decrease in its functional activity. Conclusions. Our experimental data on the morphological changes of the pineal gland confirm the conclusion about a stable, possibly irreversible, decrease in gland function in epilepsy due to damage and disruption of the structure of its cells. Given the polyfunctionality of melatonin, its deficiency can be one of the causes of changes in neural networks, impaired permeability of synaptic membranes, and as a consequence, increased epileptic activity of neurons.

Research progresses on the effects of heavy metals on the circadian clock system.

Environmental pollution with heavy metals is widespread, thus increasing attention has been paid to their toxic effects. Recent studies have suggested that heavy metals may influence the expression of circadian clock genes. Almost all organs and tissues exhibit circadian rhythms. The normal circadian rhythm of an organism is maintained by the central and peripheral circadian clock. Thus, circadian rhythm disorders perturb normal physiological processes. Here, we review the effects of heavy metals, including manganese, copper, cadmium, and lead, on four core circadian clock genes, i.e.,ARNTL, CLOCK, PER, and CRY genes.

TEKANAN DARAH SISTOLIK LEBIH TINGGI PADA SORE DARIPADA PAGI HARI PADA USIA 45-65 TAHUN

Blood pressure is the pressure of the blood pumped by the heart against the walls of the arteries and is divided into systolic and diastolic. Blood pressure decreases 10% in the evening at normal circadian rhythms and rises again in the morning. Insomnia is one of the factors that can affect blood pressure. This study aims to look at differences in morning and evening blood pressure at the age of 45–65 years. The research method uses observational analytic with a cross sectional approach. Collecting samples using consecutive non-probability sampling. Subjects aged 45–65 were 301 people. Blood pressure was measured in the morning and evening. Insomnia data obtained based on a questionnaire. The statistical test used paired t test with a significance of p &lt;0.05. The results showed a significant difference between morning and evening systolic blood pressure (P = 0,023), but there was no difference between morning and evening diastolic blood pressure (P = 0,224). There is a relationship between insomnia and morning blood pressure (p=0,001). The conclusion from the research results is that systolic blood pressure in the afternoon is higher than in the morning. Morning blood pressure is associated with difficulty sleeping at night.&#x0D;

Disruption in the regulation of casein kinase 2 in circadian rhythm leads to pathological states: cancer, diabetes and neurodegenerative disorders.

Circadian rhythm maintains the sleep-wake cycle in biological systems. Various biological activities are regulated and modulated by the circadian rhythm, disruption of which can result in onset of diseases. Robust rhythms of phosphorylation profiles and abundances of PERIOD (PER) proteins are thought to be the master keys that drive circadian clock functions. The role of casein kinase 2 (CK2) in circadian rhythm via its direct interactions with the PER protein has been extensively studied; however, the exact mechanism by which it affects circadian rhythms at the molecular level is not known. Here, we propose an extended circadian rhythm model in Drosophila that incorporates the crosstalk between the PER protein and CK2. We studied the regulatory role of CK2 in the dynamics of PER proteins involved in circadian rhythm using the stochastic simulation algorithm. We observed that variations in the concentration of CK2 in the circadian rhythm model modulates the PER protein dynamics at different cellular states, namely, active, weakly active, and rhythmic death. These oscillatory states may correspond to distinct pathological cellular states of the living system. We find molecular noise at the expression level of CK2 to switch normal circadian rhythm to any of the three above-mentioned circadian oscillatory states. Our results suggest that the concentration levels of CK2 in the system has a strong impact on its dynamics, which is reflected in the time evolution of PER protein. We believe that our findings can contribute towards understanding the molecular mechanisms of circadian dysregulation in pathways driven by the PER mutant genes and their pathological states, including cancer, obesity, diabetes, neurodegenerative disorders, and socio-psychological disease.

Circadian rhythm disturbance and delirium in ICU patients: a prospective cohort study

BackgroundPatients treated in the intensive care unit (ICU) may experience a reversal of day and night. The circadian rhythm in ICU patients can be disturbed.MethodsTo explore the relationship between ICU delirium and the circadian rhythms of melatonin, cortisol and sleep. A prospective cohort study was carried out in a surgical ICU of a tertiary teaching hospital. Patients who were conscious during the ICU stay after surgery and were scheduled to stay in the ICU for more than 24 h were enrolled. Serum melatonin and plasma cortisol levels were measured three times a day by drawing arterial blood on the first three days after ICU admission. Daily sleep quality was assessed by the Richard-Campbell Sleep Questionnaire (RCSQ). The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) was performed twice a day to screen for ICU delirium.ResultsA total of 76 patients were included in this study, and 17 patients developed delirium during their ICU stay. Melatonin levels were different at 8:00 (p = 0.048) on day 1, at 3:00 (p = 0.002) and at 8:00 (p = 0.009) on day 2, and at all three time points on day 3 (p = 0.032, 0.014, 0.047) between delirium and non-delirium patients. The plasma cortisol level in the delirium patients was significantly lower than that in the non-delirium patients at 16:00 on day 1 (p = 0.025). The changes in melatonin and cortisol secretion levels exhibited obvious biological rhythmicity in non-delirium patients (p < 0.001 for melatonin, p = 0.026 for cortisol), while no rhythmicity was found in melatonin and cortisol secretion levels in the delirium group (p = 0.064 for melatonin, p = 0.454 for cortisol). There was no significant difference in RCSQ scores in the first three days between the two groups.ConclusionsThe disturbance of the circadian rhythm of melatonin and cortisol secretion was associated with the development of delirium in ICU patients. Clinical staff should pay more attention to the importance of maintaining patients’ normal circadian rhythms in the ICU.Trial registrationThe study was registered with the US National Institutes of Health ClinicalTrials.gov(NCT05342987) (25/04/2022).