Circadian Rhythm Disturbances Research Articles

The Circadian Clock as a Potential Biomarker and Therapeutic Target in Gastrointestinal Cancers.

The circadian clock consists of a hierarchical multi-oscillator network of intracellular and intercellular mechanisms throughout the body that contributes to anticipating metabolic activity and maintaining system homeostasis in response to environmental cues and intrinsic stimuli. Over the past few years, genetic variations of core clock genes have been associated with cancer risk in several epidemiological studies. A growing number of epidemiological research studies have demonstrated a direct correlation between the disturbance of circadian rhythms and the growth of tumors, indicating that shift workers are more susceptible to malignancies of the colon, prostate, ovarian, breast, lung, and liver. One of the most related cancers with circadian rhythm is Gastrointestinal (GI) cancer, which is a leading cause of cancer-related mortality nowadays. The aim of this review was to demonstrate the effect of the clock gene network on the growth of GI cancer, providing molecular targets for GI cancer treatment, possible prognostic biomarkers, and guidance for treatment choices.

Influence of circadian rhythm and sleep schedules on depressive symptoms among adolescents in China

ABSTRACT Circadian rhythm (24-hour period of physiological and behavioral changes) is the basis of the overall health, including mood and health. This study aimed to explore the influence of circadian rhythm and sleep schedules on depressive symptoms in Chinese adolescents. In this cross-sectional study, 841 middle school students were recruited and divided into two groups (depressive group, DG, n = 210, and control group, n = 631) depending on the total score of The Center for Epidemiological Studies Depression Scale for Children (CES-DC). The circadian rhythm and sleep quality among adolescents were evaluated by using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) and Self-rating scale of Sleep (SRSS) scales. Furthermore, correlation analysis and logistic regression analysis were used to determine the effects of demographic factors, sleeping arrangement, sleep quality, and circadian rhythm on depressive symptoms. The DG group’s CES-DC, BRIAN and SRSS scores were significantly higher than the control group’s. Higher scores of BRIAN and SRSS were risk factors for depressive symptoms in Chinese adolescents. Attending a day school and waking up later on weekends may be weak protective factors. Our results suggest that circadian rhythm disturbance, sleep quality, and sleeping arrangement have a significant influence on depressive symptoms among adolescents in China.

Melatonin protects zebrafish pancreatic development and physiological rhythms from sodium propionate-induced disturbances via the hypothalamic-pituitary-thyroid axis.

The widespread use of sodium propionate as a preservative in food may affect public health. We aimed to assess the effects of sodium propionate on circadian rhythms and pancreatic development in zebrafish and the possible underlying mechanisms. In this experiment, we analyzed the relationship between circadian rhythms and pancreatic development and then revealed the role of the thyroid endocrine system in zebrafish. The results showed that sodium propionate interfered with the rhythmic behavior of zebrafish, and altered the expression of important rhythmic genes. Experimental data revealed that pancreatic morphology and developmental genes were altered after sodium propionate exposure. Additionally, thyroid hormone levels and key gene expression associated with the hypothalamic-pituitary-thyroid axis were significantly altered. Melatonin at a concentration of 1 μmol L-1, with a mild effect on zebrafish, observably alleviated sodium propionate-induced disturbances in circadian rhythms and pancreatic development, as well as regulating the thyroid system. Melatonin, while modulating the thyroid system, significantly alleviates sodium propionate-induced circadian rhythm disturbances and pancreatic developmental disorders. We further revealed the deleterious effects of sodium propionate as well as the potential therapeutic effects of melatonin on circadian rhythm, pancreatic development and the thyroid system. © 2024 Society of Chemical Industry.

Sleep disturbance in clinical and preclinical scrapie-infected sheep measured by polysomnography

Neurodegenerative diseases are characterised by neuronal loss and abnormal deposition of pathological proteins in the nervous system. Among the most common neurodegenerative diseases are Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease and transmissible spongiform encephalopathies (TSEs). Sleep and circadian rhythm disturbances are one of the most common symptoms in patients with neurodegenerative diseases. Currently, one of the main objectives in the study of TSEs is to try to establish an early diagnosis, as clinical signs do not appear until the damage to the central nervous system is very advanced, which prevents any therapeutic approach. In this paper, we provide the first description of sleep disturbance caused by classical scrapie in clinical and preclinical sheep using polysomnography compared to healthy controls. Fifteen sheep classified into three groups, clinical, preclinical and negative control, were analysed. The results show a decrease in total sleep time as the disease progresses, with significant changes between control, clinical and pre-clinical animals. The results also show an increase in sleep fragmentation in clinical animals compared to preclinical and control animals. In addition, sheep with clinical scrapie show a total loss of Rapid Eye Movement sleep (REM) and alterations in Non Rapid Eyes Movement sleep (NREM) compared to control sheep, demonstrating more shallow sleep. Although further research is needed, these results suggest that prion diseases also produce sleep disturbances in animals and that polysomnography could be a diagnostic tool of interest in clinical and preclinical cases of prion diseases.

Differential Role for the Clock Gene, BMAL1, on Kidney Function in Male versus Female Rats

Many activities of modern life, such as social visits with friends at night, long working hours, jet lag, and shift work cause circadian rhythm disturbances, which increase the risk of renal decline and eventual disease. Chronic kidney disease (CKD) is defined by decreases in glomerular filtration rate (GFR) which is higher during the daytime and lower at night in healthy individuals. Prior studies indicate that processes critical for maintaining blood pressure ( e.g. autoregulation) contribute to this time-of-day-dependence mediated by a molecular timekeeping mechanism known as the molecular circadian clock that resides in all tissues including the kidney. We hypothesized that loss of the molecular clock would impair normal kidney physiology through misalignment of functional rhythms with normal environmental patterns associated with day and night. We used a rat model of circadian disruption to interrogate our hypothesis. Male and female brain and muscle ARNT-like protein 1 knockout (BMAL1 KO) and littermate control (CON) rats aged 12-14 weeks underwent GFR measurements using FITC-labeled sinistrin clearance at two times of the day corresponding to the dark (active) and light (inactive) periods. Following GFR measurements, rats were placed in metabolic cages with food to record water intake and urine excretion over 12h active and inactive periods. Implantable telemeters were used for 24h measurement of systolic and diastolic blood pressure, locomotor activity and body temperature. Autoregulatory behavior was assessed using the isolated juxtamedullary nephron preparation to determine afferent arteriole diameter responses to changes in perfusion pressure. Diurnal measurements of GFR revealed that male BMAL1 KO rats had a significantly lower GFR in the active period as compared to CON males (1.87±0.37 vs 2.55±0.47 ml/min/100g; 2-way ANOVA, p<0.05; n=8-9). As a result, there was no diurnal variation in the KO males as seen in the CON males (Δ GFR 0.63±0.24 vs 0.04±0.21 ml/min/100g/12h CON vs KO respectively) (Sidak post-hoc, p<0.05; n=8-9) in parallel with a lack of diurnal variation in urine volume and Na excretion. Both male (n=8) and female (n=6-9) BMAL1 KO rats also displayed a significantly lower 24h mean arterial pressure (Males; 103±1 vs 107±1 mmHg, p<0.05; Females; 110±1 vs 100±2 mmHg, p<0.05) compared to CON with diurnal variation and autoregulatory reactivity preserved. Male BMAL1 KO rats consumed significantly more water compared to CON (n=5-9, 22.5±5.4 vs 14.7±4.0 mL/12h, p<0.05) concomitant with increased urine excretion (n=5-9, 13.3±6 vs 4.2±0.8 mL/12h, p<0.05) and reduced urine osmolality (n=5-7, 967±398 vs 2140±811 mmol/kg, p<0.05) regardless of time of day. Taken together these data suggest that BMAL1 is necessary for maintaining renal functional rhythms and urine concentrating ability in a sex-dependent manner. R01 DK134562 P01 HL158500. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

CHRONOTYPE AND DAILY FUNCTIONING OF PATIENTS WITH DIFFERENT MOTOR SUBTYPES OF PARKINSON DISEASE

Introduction. Sleep and circadian rhythm disturbances can occur at any stage of Parkinson disease (PD) and significantly affect quality of life. Chronotypes of patients with PD are associated with different phenotypes, in particular with the motor subtype. Thus, we hypothesized that patients with different motor subtypes of PD may have differences in the distribution of chronotypes and patterns of daily activity. Methods and materials. We conducted clinical research on the basis of the Centre for Parkinson Disease and Neurodegenerative Diseases of the Department of Neurological Diseases of Poltava State Medical University. PD was verified according to the recommendations of the International Movement Disorders and Parkinson's Disease Society. The motor subtype of PD was determined by the Stebbin method, which is based on the calculation of the Stebbins coefficient by the sum of the Unified PD Rating Scale scores. The examined patients were divided into 3 groups according to the motor subtype of PD: group 1 (n = 38) - patients with PD subtype with the predominance of postural instability and gait disorders (PIGD); group 2 (n = 26) - patients with PD subtype with the predominance of tremor and mixed subtype; control group (n = 30) - conditionally healthy individuals without CNS lesions. Circadian patterns were analyzed using the Munich Chronotype Questionnaire (MCTQ). Results. It was found that in PD patients sleep onset and time of getting out of bed was later (p<0.001 and p=0.042, respectively), sleep latency was longer (p<0.001), sleep duration was shorter (p=0.001), the mid-sleep corresponded to a later time (p<0.001). Patients with the PIGD subtype had a later time of getting out of bed (p=0.038), longer sleep inertia (p<0.001), shorter sleep duration (p<0.001), and later mid-sleep time (p=0.028). We have shown the tendency of patients with PD, mostly in the PIGD subtype, to later chronotypes (p<0.001). Light exposure indirectly moderately correlated with mid-sleep in all study groups. It was found that both the motor subtype (p<0.001) and the level of light exposure during the day (p<0.001) statistically significantly affect the mid-sleep. Conclusion. Thus, we have found that patients with PD differ from age-matched controls without neurodegenerative diseases by chronotype and circadian pattern of functioning. The motor subtype of the disease is associated with circadian differences, namely, the PIGD subtype is associated with shorter sleep duration, a predisposition to a later chronotype, and longer sleep inertia.

Selective orexin 2 receptor blockade alleviates cognitive impairments and the pathological progression of Alzheimer's disease in 3xTg-AD mice.

The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid β (Aβ) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests. Then, immunohistochemistry, western blotting and ELISA were used to detect Aβ deposition, tau phosphorylation and neuroinflammation, and electrophysiological and wheel-running activity recording were recorded to observe hippocampal synaptic plasticity and circadian rhythm. The results showed that OX2R blockade ameliorated cognitive dysfunction, improved LTP depression, increased the expression of PSD-95, alleviated anxiety- and depression-like behaviors and circadian rhythm disturbances in 3xTg-AD mice, and reduced Aβ pathology, tau phosphorylation and neuroinflammation in the brains of 3xTg-AD mice. These results indicated that chronic OX2R blockade exerts neuroprotective effects in 3xTg-AD mice by reducing AD pathology at least partly through improving circadian rhythm disturbance and the sleep-wake cycle and that OX2R might be a potential target for the prevention and treatment of AD; however, the potential mechanism by which OX2R exerts neuroprotective effects on AD needs to be further investigated.

Prospective study of the association between chronotypes and depressive symptoms in Chinese university students: Moderating effects of PER1 gene DNA methylation

ABSTRACT Most studies have shown a link between chronotypes and mental health and have identified evening chronotypes (E-types) as a potential risk for depressive symptoms. However, the mechanisms behind this association remain unknown. Abnormal expression of the PER1 gene was not only associated with circadian rhythm disturbance, but also closely related to mental illness. Therefore, this study aimed to examine the association of chronotype with depressive symptoms, and further explore the moderating effects of the PER1 gene DNA methylation on chronotypes and depressive symptoms in Chinese university students. In a stratified cluster sampling design, chronotype and depressive symptoms were assessed in 1 042 university students from 2 universities in a two-year prospective survey from April 2019 to October 2020. The survey was conducted once every 6 months, corresponding to the time points in April 2019 (T0), October 2019 (T1), April 2020 (T2), and October 2020 (T3). At T0, the Morning and Evening Questionnaire 5 (MEQ-5) was adopted to assess chronotype. At T0-T3, the Patient Health Questionnaire 9 (PHQ-9) was adopted to investigate depressive symptoms. Meanwhile, at T0, participants were subjected to a health check-up trip in the hospital, and blood samples were taken from the students to measure the PER1 gene DNA methylation levels. Binary logistic regression was used to analyze the association of chronotypes with depressive symptoms. The depression/total depression group was coded as 1, while the remaining participants was defined as one group, and was coded as 0. The PROCESS plug-in of SPSS software was used to analyze the moderating effects of PER1 gene DNA methylation on the association of chronotype with depressive symptoms. After adjusting for covariates, the results indicated that T0 E-types were positively correlated with T0-T3 depression/total depression in female university students. Furthermore, the PER1 gene DNA methylation has negative moderating effects between T0 chronotype and T3 depressive symptoms and has a sex difference. This study can provide more favorable scientific value for the prevention and control of depression in university students.

Formulating Treatment to Cure Alzheimer's Dementia: Approach #2.

There are two generic approaches to curing any medical condition. The first one treats every patient for all the known possible causes that contribute to pathogenesis; the second one individualizes potentially curative therapy by only identifying in each separate patient the components of pathogenesis that are actually operative and treating those. This article adopts the second approach for formulating a cure for Alzheimer's dementia (AD). The components of AD's pathogenesis are, in alphabetical order, as follows: circadian rhythm disturbances, depression, diabetes and insulin resistance, dyslipidemia, hypertension, inflammation, metabolic syndrome, mitochondrial dysfunction, nutritional deficiencies, TGF-β deficiency, underweight, vascular abnormalities, and Wnt/β-catenin deficiency. For each component, data are described that show the degree to which its prevalence is higher in patients with mild cognitive impairment (MCI) who did not revert to having normal cognition than in those who did because the former group is the pool of patients in which future AD may develop. Only addressing the components that are present in a particular individual potentially is a curative strategy. Published data indicate that curative therapy requires the number of such components that are addressed to be ≥3. Although structural brain changes cannot be directly addressed, the impaired neural tracts result from many of the reversible causal elements, so correcting them will benefit these tracts.

Effect of exercise based interventions on sleep and circadian rhythm in cancer survivors-a systematic review and meta-analysis.

Disrupted circadian rhythm commonly reported in cancer survivors is closely associated with cancer related fatigue, sleep disturbances and compromised quality of life. As more cancer survivors request non-pharmacological treatment strategies for the management of their chronic sleep-related symptoms, there is a need for meta-analyses of various interventions such as exercise on sleep and circadian rhythm disturbances. A search for RCT's was conducted in April 2020 and updated in July 2023 using relevant keywords for cancer, sleep, circadian rhythm and exercise interventions on PubMed, Scopus, Web of Science, PEDro and CINAHL. Thirty-six studies were included for qualitative analysis and 26, for meta-analysis. Thirty-five studies analyzed sleep outcomes, while five analyzed circadian rhythm. RCT's studying the effect of aerobic exercise, resistance exercise, combined aerobic and resistance exercise, physical activity, yoga, or tai chi were included. Meta-analysis results showed significant exercise-related improvements on sleep quality assessed by Pittsburgh Sleep Quality index (PSQI) (SMD = -0.50 [-0.87, -0.13], p=0.008), wake after sleep onset (WASO) (SMD = -0.29 [-0.53, -0.05], p=0.02) and circadian rhythm, assessed by salivary cortisol levels (MD = -0.09 (95% CI [-0.13 to -0.06]) mg/dL, p<0.001). Results of the meta-analysis indicated that exercise had no significant effect on sleep efficiency, sleep onset latency, total sleep time and circadian rhythm assessed by accelerometry values. While some sleep and circadian rhythm outcomes (PSQI, WASO and salivary cortisol) exhibited significant improvements, it is still somewhat unclear what exercise prescriptions would optimize different sleep and circadian rhythm outcomes across a variety of groups of cancer survivors. As exercise does not exacerbate cancer-related circadian rhythm and sleep disturbances, and may actually produce some significant benefits, this meta-analysis provides further evidence for cancer survivors to perform regular exercise.

Biological Clock Genes are Crucial and Promising Biomarkers for the Therapeutic Targets and Prognostic Assessment in Gastric Cancer.

Gastric cancer is one of the major public health problems worldwide. Circadian rhythm disturbances driven by circadian clock genes play a role in the development of cancer. However, whether circadian clock genes can serve as potential therapeutic targets and prognostic biomarkers for gastric cancer remains elusive. In this study, we comprehensively analyzed the potential relationship between circadian clock genes and gastric cancer using online bioinformatics databases such as GEPIA, cBioPortal, STRING, GeneMANIA, Metascape, TIMER, TRRUST, and GEDS. Biological clock genes are expressed differently in human tumors. Compared with normal tissues, only PER1, CLOCK, and TIMELESS expression differences were statistically significant in gastric cancer (p < 0.05). PER1 (p = 0.0169) and CLOCK (p = 0.0414) were associated with gastric cancer pathological stage (p < 0.05). Gastric cancer patients with high expression of PER1 (p = 0.0028) and NR1D1 (p = 0.016) had longer overall survival, while those with high expression of PER1 (p = 0.042) and NR1D1 (p = 0.016) had longer disease-free survival. The main function of the biological clock gene is related to the circadian rhythms and melatonin metabolism and effects. CLOCK, NPAS2, and KAT2B were key transcription factors for circadian clock genes. In addition, we also found important correlations between circadian clock genes and various immune cells in the gastric cancer microenvironment. This study may establish a new gastric cancer prognostic indicator based on the biological clock gene and develop new drugs for the treatment of gastric cancer using biological clock gene targets.

A Protocol for Evaluating Digital Technology for Monitoring Sleep and Circadian Rhythms in Older People and People Living with Dementia in the Community.

Sleep and circadian rhythm disturbance are predictors of poor physical and mental health, including dementia. Long-term digital technology-enabled monitoring of sleep and circadian rhythms in the community has great potential for early diagnosis, monitoring of disease progression, and assessing the effectiveness of interventions. Before novel digital technology-based monitoring can be implemented at scale, its performance and acceptability need to be evaluated and compared to gold-standard methodology in relevant populations. Here, we describe our protocol for the evaluation of novel sleep and circadian technology which we have applied in cognitively intact older adults and are currently using in people living with dementia (PLWD). In this protocol, we test a range of technologies simultaneously at home (7-14 days) and subsequently in a clinical research facility in which gold standard methodology for assessing sleep and circadian physiology is implemented. We emphasize the importance of assessing both nocturnal and diurnal sleep (naps), valid markers of circadian physiology, and that evaluation of technology is best achieved in protocols in which sleep is mildly disturbed and in populations that are relevant to the intended use-case. We provide details on the design, implementation, challenges, and advantages of this protocol, along with examples of datasets.

Correlation between Poststroke Insomnia and Circadian Rhythm Disturbance Research Progress

Correlation between Poststroke Insomnia and Circadian Rhythm Disturbance Research Progress

The Impact of Screen Time on Sleep Patterns in School-Aged Children: A Cross-Sectional Analysis.

In a world filled with technology, there's concern about the impact of screen time on children and teenagers. A recent study of 11,875 children aged nine to 10 in the US explored how screen time affects mental health, behaviour, school performance, sleep, and friendships. The results indicate that more screen time is mildly linked to worse mental health, more behaviour problems, lower academic performance, and poorer sleep, but slightly better peer relationships. However, these connections were weak, with socioeconomic status (SES) having a stronger influence on these outcomes. The study doesn't prove that screen time causes these issues, suggesting that increased screen time might not be directly harmful to children in this age group. The research adds to the understanding of how screen time impacts children's well-being and highlights the importance of promoting healthy habits. Our study aims to add to this literature by examining how screen time impacts sleep quality, dream recall, and academic performance in school-aged children. Understanding the potential consequences of screen time is crucial for promoting healthy habits and ensuring the overall well-being of children. Our research seeks to provide further insights into the relationship between screen time and key aspects of children's lives as its prevalence continues to rise. The research incorporates a cohort of 1000 school-aged children, bifurcated evenly into two categories based on their daily screen exposure: a low screen time group (less than one hour daily, n = 500) and a high screen time group (over three hours daily, n = 500). The study probes into the correlation between screen time and various health parameters, such as sleep patterns, dream recall, and academic prowess. The analysis showed that children with low screen time had better sleep efficiency (90% vs. 75%), more frequent dream recall (70% vs. 30%), fewer nocturnal awakenings (0.5 vs. 1.5 times weekly), less daytime sleepiness (20% vs. 60%), and higher physical activity levels (60 vs. 30 minutes per day) compared to those with high screen time. They also had less weekend sleep variability (1.2 hours) and a lower risk of circadian rhythm disturbances (20% increased risk in the high screen time group). Additionally, a screen-free bedroom was more common in the low screen time group (85% vs. 30%), and parental involvement in sleep routines was higher (90% vs. 40%). Academically, the low screen time group achieved higher grades ('A' to 'A+' vs. 'B'), and they had more face-to-face social interactions (two vs. one hour per day). Escalating screen time is correlated with detrimental impacts on sleep efficiency, dream recall, physical activity, circadian rhythms, and academic performance in school-aged children. Fostering a screen-free bedroom environment and augmenting parental involvement in sleep routines may alleviate these adverse effects.

Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder and/or pelvic pain, increased urinary urgency and frequency and nocturia. The pathophysiology of IC/BPS is poorly understood, and theories include chronic inflammation, autoimmune dysregulation, bacterial cystitis, urothelial dysfunction, deficiency of the glycosaminoglycan (GAG) barrier and urine cytotoxicity. Multiple treatment options exist, including behavioural interventions, oral medications, intravesical instillations and procedures such as hydrodistension; however, many clinical trials fail, and patients experience an unsatisfactory treatment response, likely owing to IC/BPS phenotype heterogeneity and the use of non-targeted interventions. Oxidative stress is implicated in the pathogenesis of IC/BPS as reactive oxygen species impair bladder function via their involvement in multiple molecular mechanisms. Kinase signalling pathways, nociceptive receptors, mast-cell activation, urothelial dysregulation and circadian rhythm disturbance have all been linked to reactive oxygen species and IC/BPS. However, further research is necessary to fully uncover the role of oxidative stress in the pathways driving IC/BPS pathogenesis. The development of new models in which these pathways can be manipulated will aid this research and enable further investigation of promising therapeutic targets.

Endocrine disruption in teleosts and amphibians is mediated by anthropogenic and natural environmental factors: implications for risk assessment.

Environmental variation in the Anthropocene involves several factors that interfere with endocrine systems of wildlife and humans, presenting a planetary boundary of still unknown dimensions. Here, we focus on chemical compounds and other impacts of anthropogenic and natural originsthat are adversely affecting reproduction and development. The main sink of these endocrine disruptors (EDs) is surface waters, where they mostly endanger aquatic vertebrates, like teleost fish and amphibians. For regulatory purposes, EDs are categorized into EATS modalities (oestrogenic, androgenic, thyroidal, steroidogenesis), only addressing endocrine systems being assessable by validated tests. However, there is evidence that non-EATS modalities-and even natural sources, such as decomposition products of plants or parasitic infections-can affect vertebrate endocrine systems. Recently, the disturbance of natural circadian light rhythms by artificial light at night (ALAN) has been identified as another ED. Reviewing the knowledge about EDs affecting teleosts and amphibians leads to implications for risk assessment. The generally accepted WHO-definition for EDs, which focuses exclusively on 'exogenous substances' and neglects parasitic infections or ALAN, seems to require some adaptation. Natural EDs have been involved in coevolutionary processes for ages without resulting in a general loss of biodiversity. Therefore, to address the 'One Health'-principle, future research and regulatory efforts should focus on minimizing anthropogenic factors for endocrine disruption. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Abstract WMP57: Systematic Reduction of Neurochecks Overnight Decreases Length of Stay and Post-Stroke Delirium

Introduction: Post-stroke delirium is common and leads to worse short- and long-term outcomes with higher 28-day modified Rankin Score (mRS), longer length of hospitalization, and increased odds of discharge to a nursing home, development of dementia, and death. Circadian rhythm disturbances have been implicated as a core mechanism in the pathogenesis of delirium as well as a common sequela of stroke. Standard of care for acute stroke patients is to receive q1h-q4h neuro checks overnight to ensure stability and these are typically continued throughout hospitalization; however, there is limited evidence to support extended use and frequent checks have been implicated in increased delirium rate. Our pilot study addresses this problem by proactively holding neuro checks overnight on clinically stable patients with the goal of promoting re-institution of circadian rhythm as a delirium prevention measure. Methods: After at least 24 hours of hospitalization, patients who were felt to be clinically stable had neuro checks discontinued overnight between the hours of 8pm and 4am and efforts were made to bundle care around these times. If patients were felt not to be stable enough to reduce neuro checks, neuro checks were continued at the frequency typical of the usual standard of care. Patients were reassessed daily to determine if they were stable for neuro check decrease. The Confusion Assessment Method (CAM) was performed each shift with a positive result indicative of delirium. Results: 290 patients over 12 months were included in the analysis (157 pre-intervention, 133 post-intervention). Demographic data did not differ significantly between groups. After the intervention was initiated, CAM positivity decreased from 34% to 23% (p=0.017). LOS decreased from 6.6 days to 5.1 days (p=0.024). mRS and NIHSS during hospitalization did not significantly change (NIHSS p=0.97, mRS p=0.38). Conclusions: After the introduction of the intervention, delirium rate and length of stay decreased significantly. In conclusion, holding neuro checks overnight for clinically stable patients may decrease delirium rate and length of stay, but require more systematic study.

Relationship between biological rhythm dysregulation and suicidal ideation in patients with major depressive disorder

BackgroundAlthough the disturbance of circadian rhythms represents a significant clinical feature of major depressive disorder (MDD), the relationship between biological rhythm disturbances and the severity of suicidal ideation in individuals with MDD remains unclear. We aimed to explore the characteristics of different biological rhythm dimensions in MDD and their association with the severity of depressive symptoms and suicidal ideation.MethodsA total of 50 MDD patients and 50 healthy controls were recruited and their general information was collected. The severity of depressive symptoms was assessed with the 17-item Hamilton Depression Rating Scale (HDRS17). The intensity of suicidal ideation was evaluated with the Beck Scale for Suicide Ideation (BSS). The Chinese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) scale was utilized to assess the participants’ biological rhythm dysregulation. Multiple logistic regression analysis was conducted to explore the relationship between biological rhythm and the risk of MDD. Multiple linear regression analysis was performed in the MDD group to investigate the relationship between different biological rhythm dimensions and suicide ideation.ResultsSignificant differences were observed between the MDD group and the control group in total BRIAN score (Z=-5.41, P < 0.001) as well as scores for each dimension. After adjusting for confounding factors, multiple logistic regression analysis revealed a significant association between total BRIAN score and the presence of MDD (OR = 1.20, 95% CI = 1.10–1.29, P < 0.001), as well as between scores in different BRIAN dimensions and the presence of MDD (activity: OR = 1.47, 95% CI = 1.24–1.74, P < 0.001; sleep: OR = 1.52, 95% CI = 1.28–1.79, P < 0.001; social: OR = 1.80, 95% CI = 1.32–2.46, P < 0.001; eating pattern: OR = 1.34, 95% CI = 1.12–1.60, P = 0.001). In patients with MDD, linear regression analysis demonstrated a positive relationship between BSS scores and BRIAN eating pattern scores (β = 0.34, P = 0.022), even after adjusting for demographic factors and the severity of depression.ConclusionsPatients with MDD exhibited significantly higher levels of dysregulation in all four biological rhythm dimensions compared to healthy controls and the degree of dysregulation was associated with the severity of depression. More importantly, dysregulation of eating pattern may increase the intensity of suicidal ideation in MDD, thus elevating the risk of suicide.

Multi-omics and single-cell sequencing analyses reveal the potential significance of circadian pathways in cancer therapy

ABSTRACT Background Circadian rhythm disturbance is an independent risk factor for cancer. However, few studies have been reported on circadian rhythm related genes (CRGs) in cancer, so it is important to further explore the impact of CRGs in pan-cancer. Research design and methods The Cancer Genome Atlas database was used to collect cancer-related data such as copy number variation, single nucleotide variants, methylation, and survival differences. Immunohistochemistry (IHC) was used to verify the expression of circadian rhythm hub genes. The circadian pathway scores (CRS) were calculated using single-sample gene enrichment analysis. TIMER and GEPIA databases were used for immune-cell integration and assessment. Single-cell sequencing data was used to evaluate the abundance of CRS in tumor microenvironment cells. Results In this study, we found that the expression of circadian pathway varies between tumors. CSNK1E was significantly up-regulated in most tumors and CRY2 was significantly down-regulated in most tumors. The protein interaction network suggested CRY2 as the core gene and IHC verified its significant low expression in KIRC. In addition, CRGs were found to be protective factors in most tumors and have the potential to act as specific immune markers in different tumors. CRS was significantly lower in abundance in most tumors. CRS was significantly associated with overall survival in tumor patients and associated with the expression of many immune cells in the tumor immune microenvironment. CRS is significantly associated with tumor mutational burden and microsatellite instability scores in most tumors and may serve as a potential immunotherapeutic marker. Conclusions The circadian rhythm pathway may be a breakthrough point in regulating the tumor microenvironment meanwhile a suitable immunotherapy method in the future.

Probiotic Supplementation With Saccharomyces boulardii and Enterococcus faecium Improves Gastric Pain and Bloating in Airline Pilots With Chronic Non-atrophic Gastritis: An Open-Label Study.

Background Commercial airline pilots (APs) are prone to upper gastrointestinal symptoms, such as epigastric pain and bloating. These issues are often linked to occupational risk factors like irregular diet, sleep disruption, and circadian rhythm disturbance. The use of probiotics to enhance intestinal health is well established, but their efficacy in treating upper gastrointestinal diseases is still debated. This is primarily due to the stomach's small resident microbiota and its low pH, which is inhospitable to most microbes. However, emerging research suggests that specific probiotic strains, such as Enterococcus faecium, can withstand acidic environments. Moreover, certain yeast species, including Saccharomyces boulardii, can survive at a low pH. Consequently, we conducted a preliminary, three-arm, randomized, open-label, dose-finding, four-week study to compare the effects of watchful waiting (WW) with the administration of an oral probiotic supplement containing S. boulardii and E. faecium in APs diagnosed with Helicobacter pylori-negative chronic non-atrophic gastritis (CNG). Methods The study included 39 APs with CNG who were randomized into three groups with a 1:1:1 ratio. The low-dose group (n = 13) received one capsule of the probiotic supplement twice daily, before meals, for four weeks. The high-dose group (n = 13) was administered two capsules of the supplement on the same schedule. The third group (n = 13) underwent WW and served as the control arm. Blinding was maintained for the examining physicians and laboratory staff, but not for the patients. All participants self-rated their experiences of gastric pain and bloating at the beginning and conclusion of the four-week treatment period. Additionally, serum levels of pepsinogen I (PGI) and pepsinogen II (PGII) were measured at these time points. Results Supplementation with probiotics significantly outperformed WW in reducing subjective gastric pain and bloating. This effect was consistent across both tested dosages, with no significant differences observed. However, only high-dose probiotics led to a statistically significant decrease in PGII levels and an increase in the PGI/PGII ratio after the four-week study period, a result not observed with low-dose probiotics. Conclusions Oral administration of S. boulardii and E. faecium demonstrated potential efficacy in reducing gastric pain and bloating symptoms in APs with CNG, as evidenced by statistically significant symptom improvement compared to the control group that did not receive the probiotic supplementation. Notably, high-dose probiotics resulted in a significant increase in the PGI/PGII ratio, indicating potential long-term cytoprotective effects on the gastric mucosa.