ArticleLiterature Review

Melatonin, sleep disturbance and cancer risk

August 2009
Sleep Medicine Reviews 13(4):257-64

DOI:10.1016/j.smrv.2008.07.007

Source
PubMed

Authors:

Tulane University

The pineal hormone melatonin is involved in the circadian regulation and facilitation of sleep, the inhibition of cancer development and growth, and the enhancement of immune function. Individuals, such as night shift workers, who are exposed to light at night on a regular basis experience biological rhythm (i.e., circadian) disruption including circadian phase shifts, nocturnal melatonin suppression, and sleep disturbances. Additionally, these individuals are not only immune suppressed, but they are also at an increased risk of developing a number of different types of cancer. There is a reciprocal interaction and regulation between sleep and the immune system quite independent of melatonin. Sleep disturbances can lead to immune suppression and a shift to the predominance in cancer-stimulatory cytokines. Some studies suggest that a shortened duration of nocturnal sleep is associated with a higher risk of breast cancer development. The relative individual contributions of sleep disturbance, circadian disruption due to light at night exposure, and related impairments of melatonin production and immune function to the initiation and promotion of cancer in high-risk individuals such as night shift workers are unknown. The mutual reinforcement of interacting circadian rhythms of melatonin production, the sleep/wake cycle and immune function may indicate a new role for undisturbed, high quality sleep, and perhaps even more importantly, uninterrupted darkness, as a previously unappreciated endogenous mechanism of cancer prevention.

Imbalanced sleep increases mortality risk by 14-34%: a meta-analysis

Article

Full-text available

Mar 2025

Sleep duration is a crucial factor influencing health outcomes, yet its relationship with mortality remains debated. In this meta-analysis, we aimed to investigate the association between short and long sleep duration and all-cause mortality in adults, including sex-specific differences. A systematic search was performed in multiple databases, including PubMed, Cochrane Central, and Web of Science, up to October 2024. Retrospective and prospective cohort studies involving adults with at least 1 year of follow-up and data on sleep duration and all-cause mortality were included. Hazard ratios were pooled using a random-effects model, with subgroup analyses performed based on sex and sleep duration categories. A total of 79 cohort studies were included, with data stratified by sex and categorized into short and long sleep durations. Short sleep duration (< 7 h per night) was associated with a 14% increase in mortality risk compared to the reference of 7–8 h, with a pooled hazard ratio of 1.14 (95% CI 1.10 to 1.18). Conversely, long sleep duration (≥ 9 h per night) was associated with a 34% higher risk of mortality, with a hazard ratio of 1.34 (95% CI 1.26 to 1.42). Sex-specific analyses indicated that both short and long sleep durations significantly elevated mortality risk in men and women, although the effect was more pronounced for long sleep duration in women. Both short and long sleep durations are associated with increased all-cause mortality, though the degree of risk varies by sex. These findings underscore the importance of considering optimal sleep duration in public health strategies aimed at enhancing longevity and highlight the need for sex-specific approaches in sleep health research.

Sleep and cancer mortality in the Cancer Prevention Study-II

Article

Full-text available

Sep 2024
CANCER CAUSE CONTROL

Purpose Sleep is a multi-dimensional human function that is associated with cancer outcomes. Previous work on sleep and cancer mortality have not investigated how this relationship varies by sex and cancer site. We investigated the association of sleep duration and perceived insomnia with site-specific and overall cancer mortality among participants in the Cancer Prevention Study–II. Methods Sleep was collected at baseline in 1982 among 1.2 million cancer-free US adults. Cancer-specific mortality was determined through 2018. We used multivariable Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals for overall and site-specific cancer mortality, stratified by sex. Results Among 983,105 participants (56% female) followed for a median of 27.9 person-years, there were 146,911 primary cancer deaths. Results from the adjusted model showed short (6 h/night) and long (8 h/night and 9–14 h/night) sleep duration, compared to 7 h/night, were associated with a modest 2%, 2%, and 5% higher risk of overall cancer mortality, respectively, and there was a significant non-linear trend (p-trend < 0.01). This non-linear trend was statistically significant among male (p-trend < 0.001) but not female (p-trend 0.71) participants. For male participants, short and long sleep were associated with higher risk of lung cancer mortality and long sleep was associated with higher risk of colorectal cancer mortality. Perceived insomnia was associated with a 3–7% lower risk of overall cancer mortality. Conclusion Sleep is important to consider in relation to sex- and site-specific cancer mortality. Future research should investigate other components of sleep in relation to cancer mortality.

Associations of clinical and modifiable behavioral risk factors with the histological progression of squamous intraepithelial lesions

Article

Full-text available

Aug 2024

Cervical cancer is the third most common cancer in women worldwide. Human papillomavirus (HPV) has been established as a cause of invasive cervical cancer. However, HPV is predominantly transient and only a minority of cases persist and progress clinically. Certain epidemiological factors have been suggested to increase the risk of HPV persistence and progression. In the present study, 893 women were investigated, with an age range from 25 to 60 years old. PAP smears and colposcopy were used for assessment. Of these women, 108 were diagnosed with squamous intraepithelial lesions (SILs) and were further divided into high-grade SIL (HSIL) and low-grade SIL (LSIL). The dietary habits, sleep patterns and gynecological histories of these participants were studied, and it was found that the probability of having <3 meals a day [odds ratio (OR), 4.35; 95% confidence interval (CI), 1.73-10.95], having an unbalanced diet (OR, 3.90; 95% CI, 1.44-10.55), breakfast skipping (OR, 6.32; 95% CI, 2.40-16.61) and disrupted sleep (OR, 4.42; 95% CI, 1.79-10.93) was significantly higher in the HSIL group compared with the probability in the LSIL group. In addition, participants who had pregnancies prior to the age of 20 were 2.85 times more likely to have more advanced disease (OR, 2.85; 95% CI, 1.22-6.71). Cervical erosion was higher in the HSIL group compared with that in the LSIL group (OR, 3.31; 95% CI, 1.36-6.96). The present study highlights the protective effects of meal numbers, nutritious diet and sleep hygiene against HPV and the progression of SIL.

Roles of Melatonin and Phyto-Melatoninas an Anti-Cancer Molecule: An Evolutionary Perspective

Article

Jul 2021

Ghosh S

Etymologically, melatonin (N-acetyl-5-methoxytryptamine) can be traced back to the origin of life. The first origin of melatonin was detected in cyano-bacteria. As considering the endosymbiont hypothesis, cyanobacteria were engulfed by the animal and plant cells. Later on, these bacteria performed the roles of mitochondria and chloroplastids in animals and plant cells respectively. Inner matrices of these organelles are having melatonin and probable function of this intra-organelle melatonin is to protect the organelles from the detrimental effects from free radicals (Reactive Oxygen Species; ROSs and Reactive Nitrogen Species; RNSs). In higher animals, melatonin is synthesized and secreted by the pineal gland mainly during the night, since light exposure suppresses its production. Other than pineal gland, melatonin is secreted from several different organs like retina, gastro-intestinal tract. The secretion of this hormone is regulated by several environmental factors like photo-period, temperature, humidity etc. Melatonin can exert its function either by as a free molecule or by its membrane bound receptors MT1 and MT2 respectively. Modulations of melatonin receptors results in stimulation of apoptosis, regulation of pro-survival signaling, inhibition on angiogenesis, metastasis, and induction of epigenetic alteration. Melatonin could also be utilized as adjuvant of cancer therapies, through reinforcing the therapeutic effects and reducing the side effects of chemotherapies or radiation. Melatonin could be an excellent candidate for prevention and treatment of several cancers, such as breast cancer, prostate cancer, gastric cancer and colorectal cancer. This review summarized the anticancer efficacy of melatonin, based on the results of epidemiological, experimental and clinical studies.

Sleep Duration and Stress Level in the Risk of Gastric Cancer: A Pooled Analysis of Case-Control Studies in the Stomach Cancer Pooling (StoP) Project

Article

Full-text available

Aug 2023

Simple Summary To our knowledge, this is the first study to address both sleep duration and psychological stress in association with GC risk. Long sleep was associated with gastric cancer, and its subsites and histological types, and stress increased the risk of noncardia cancer in particular. The two exposures exerted an independent effect on GC. These findings contribute to providing evidence for the role of sleep and stress in gastric cancer epidemiology. Abstract The association between sleep and stress and cancer is underinvestigated. We evaluated these factors in association with gastric cancer (GC). Five case-control studies from the Stomach Cancer Pooling (StoP) Project were included. We calculated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for sleep duration and stress level in association with GC through multiple logistic regression models adjusted for several lifestyle factors. The analysis included 1293 cases and 4439 controls, 215 cardia and 919 noncardia GC, and 353 diffuse and 619 intestinal types. Sleep duration of ≥9 h was associated with GC (OR =1.57, 95% CI = 1.23–2.00) compared to 8 h. This was confirmed when stratifying by subsite (noncardia OR = 1.59, 95% CI = 1.22–2.08, and cardia OR = 1.63, 95% CI = 0.97–2.72) and histological type (diffuse OR = 1.65, 95% CI = 1.14–2.40 and intestinal OR = 1.24, 95% CI = 0.91–1.67). Stress was associated with GC (OR = 1.33, 95% CI = 1.18–1.50, continuous). This relationship was selectively related to noncardia GC (OR = 1.28, 95% 1.12–1.46, continuous). The risk of diffuse (OR = 1.32, 95% CI = 1.11–1.58) and intestinal type (OR = 1.23, 95% CI = 1.07–1.42) were higher when stress was reported. Results for the association between increasing level of stress and GC were heterogeneous by smoking and socioeconomic status (p for heterogeneity = 0.02 and <0.001, respectively). In conclusion, long sleep duration (≥9 h) was associated with GC and its subtype categories. Stress linearly increased the risk of GC and was related to noncardia GC.

The Correlation of Sleep Disturbance and Location of Glioma Tumors: A Narrative Review

Article

Full-text available

Jun 2023

Sleep disturbance can occur when sleep centers of the brain, regions that are responsible for coordinating and generating healthy amounts of sleep, are disrupted by glioma growth or surgical resection. Several disorders cause disruptions to the average duration, quality, or patterns of sleep, resulting in sleep disturbance. It is unknown whether specific sleep disorders can be reliably correlated with glioma growth, but there are sufficient numbers of case reports to suggest that a connection is possible. In this manuscript, these case reports and retrospective chart reviews are considered in the context of the current primary literature on sleep disturbance and glioma diagnosis to identify a new and useful connection which warrants further systematic and scientific examination in preclinical animal models. Confirmation of the relationship between disruption of the sleep centers in the brain and glioma location could have significant implications for diagnostics, treatment, monitoring of metastasis/recurrence, and end-of-life considerations.

Research Progress, Hotspots, and Evolution of Nighttime Light Pollution: Analysis Based on WOS Database and Remote Sensing Data

Article

Full-text available

Apr 2023

With the rapid development of the global economy, the over-expansion of outdoor artificial light at night (ALAN) in cities has led to increasingly severe light pollution worldwide. More and more studies have paid attention to the problem of light pollution, but there is still a lack of systematic literature review on nighttime light pollution in terms of research progress, hotspots, and its evolutions. For this purpose, this study firstly analyzed current research actuality and trends about nighttime light pollution via a comprehensive retrospect of pertinent literature and summarized the adverse effects and monitoring technologies of light pollution by VOSviewer-based keyword co-occurrence technique. Additionally, the study explored the variation tendency of nighttime light pollution in typical countries from 2013 to 2021 based on remote-sensing data and further proposed management suggestions to protect the nighttime environment. The results indicate that the research popularity of nighttime light pollution has been increasing recently, especially after the opening of diversified remote-sensing data in 2012; the main research topics are dominated by adverse effects and monitoring technologies, where the latter is represented by ground survey and remote-sensing observation; the total levels of ALAN intensity are relatively high in most developed countries, but the mean and per capita values are decreasing, and the above phenomenon in developing countries show the opposite trend. This study expects to integrate the literature analysis method and remote-sensing data to demonstrate the research status and variation trends of nighttime light pollution systematically so as to provide scientific references for the assessment and management of the nighttime light environment.

Subjective and objective fatigue dynamics in air traffic control

Article

Feb 2025
IND HEALTH

Fatigue is a longstanding issue in air traffic control (ATC), closely associated with shift work and time-related factors. However, the dynamics of fatigue across morning, evening, and night shifts in an area control center (ACC) remain largely underexplored. This study examined sleep duration and fatigue progression across different shift types. Both objective (three-minute Psychomotor Vigilance Task, PVT-B) and subjective (Stanford Sleepiness Scale, SSS) measures were conducted at the beginning, middle, and end of each shift. Results indicated that pre-shift sleep duration was shortest before night shifts, likely increasing sleep pressure and reducing alertness during the window of circadian low (WOCL). Subjective fatigue remained stable throughout morning shifts but increased towards the end of evening shifts, reflecting circadian influences. Night shifts exhibited peak fatigue during the WOCL, driven primarily by circadian rhythms rather than task load. Objective measures revealed a mid-shift decline in performance, with only partial recovery in the latter half of night shifts. Compared to day shifts, night shifts resulted in significantly higher fatigue levels, underscoring the critical role of circadian rhythms in fatigue dynamics. These findings highlight the need for targeted fatigue mitigation strategies that address circadian vulnerabilities and irregular sleep patterns in ATC shift systems.

A narrative review of sleep and breast cancer: from epidemiology to mechanisms

Article

Full-text available

Dec 2024
CANCER CAUSE CONTROL

Breast cancer is the leading cause of cancer-related death and the most common cancer among women worldwide. It is crucial to identify potentially modifiable risk factors to intervene and prevent breast cancer effectively. Sleep factors have emerged as a potentially novel risk factor for female breast cancer. Current epidemiologic studies suggest a significant impact of sleep factors on breast cancer. Exposure to abnormal sleep duration, poor sleep quality, sleep disorders, sleep medication use, or night shift work can increase the risk of breast cancer by decreasing melatonin secretion, disrupting circadian rhythm, compromising immune function, or altering hormone levels. However, there are still controversies regarding the epidemiologic association, and the underlying mechanisms have yet to be fully elucidated. This paper summarizes the epidemiologic evidence on the associations between sleep factors, including sleep duration, sleep quality, sleep disorders, sleep medication use, sleep habits, and night shift work, and the development of breast cancer. The potential mechanisms underlying these associations were also reviewed.

Night shift work and prostate cancer: a large cohort study from UK Biobank and Mendelian randomisation study

Article

Full-text available

Dec 2024

Objective The global concern regarding the health implications of night shift work has escalated. Nevertheless, variations exist in the observed association between night shift work and prostate cancer (PCa). This study aims to systematically explore the association between night shift work and the risk of PCa. Design Cohort study and Mendelian randomisation (MR) study were used. Setting Cohort study data was from the UK Biobank (UKB). MR study using data was from the Finngen study and UKB through the Integrative Epidemiology Unit (IEU) Open Genome-Wide Association Study Project. Participants Participants without prior PCa in paid employment or self-employment were include in the current work schedule cohort, participants without PCa who provided employment history formed the lifetime night shift work cohort. Main outcome measures The outcome, incident PCa, was obtained from cancer register through linkage to national cancer databases. National cancer registries centralised information received from separate regional cancer centres around the UK. Results A total of 130 853 participants were included in the current work schedule cohort, while the lifetime night shift work cohort comprised 49 511 participants. Over a median follow-up duration of 13.9 years, the current work schedule cohort witnessed 4993 incident cases of PCa, while the lifetime night shift work cohort recorded 2022 PCa cases. In the analysis of the current work schedule, final model showed that no significant association was found between shift work and PCa risk, whether it involved shift but no night shifts (HR 0.96, 95% CI 0.85 to 1.08), some night shifts (HR 1.16, 95% CI 0.99 to 1.33) and usual night shifts (HR 1.01, 95% CI 0.85 to 1.19). In the analysis of the average frequency of night shift work, final model showed no significant impact of different night shift frequencies (<3/month: HR 0.97, 95% CI 0.73 to 1.29; 3–8/month: HR 0.99, 95% CI 0.83 to 1.19; >8/month: HR 0.89, 95% CI 0.73 to 1.07) on the risk of PCa. No significant association was found for either <10 years (HR 0.89, 95% CI 0.72 to 1.09) or ≥10 years (HR 1.00, 95% CI 0.86 to 1.16) of night shift work. Subsequent subgroup and sensitivity analyses demonstrated consistent results without significant alterations. Furthermore, in the two-sample MR analysis, no statistically significant causal relationship was identified between night shift work and the incidence of PCa. Conclusion In both the cohort studies and MR analysis, our investigation did not find any association between night shift work and PCa.

Microbiome-Based Therapeutics for Insomnia

Article

Full-text available

Dec 2024
INT J MOL SCI

Insomnia poses considerable risks to both physical and mental health, leading to cognitive impairment, weakened immune function, metabolic dysfunction, cardiovascular issues, and reduced quality of life. Given the significant global increase in insomnia and the growing scientific evidence connecting gut microbiota to this disorder, targeting gut microbiota as an intervention for insomnia has gained popularity. In this review, we summarize current microbiome-based therapeutics for insomnia, including dietary modifications; probiotic, prebiotic, postbiotic, and synbiotic interventions; and fecal microbiota transplantation. Moreover, we assess the capabilities and weaknesses of these technologies to offer valuable insights for future studies.

The effects of overnight sleep deprivation or total sleep deprivation on the body

Article

Full-text available

Jun 2024

Nataliya Volotovska

This analytical and scientific work explores the multifaceted effects of overnight and total sleep deprivation on the human body. Sleep deprivation, increasingly prevalent due to the modern pace of life, significantly impacts various physiological systems including the cardiovascular, nervous, reproductive, digestive, and immune systems. It also leads to hormonal imbalances and cognitive impairments, manifesting in serious somatic and mental illnesses. Despite extensive research, the mechanisms through which sleep influences these body systems remain incompletely understood. This review aims to synthesize current knowledge on the subject, emphasizing the importance of early identification and treatment of sleep disorders to prevent a range of health issues and enhance overall well-being.

Sleep and risk of hip fracture and falls among middle-aged and older Chinese

Article

Full-text available

Oct 2024

The study aimed to assess the prospective associations between sleep duration, sleep restfulness, midday napping and hip fracture (HF) and falls in a nationally representative Chinese population. Data were from the China Health and Retirement Longitudinal Study which was conducted from 2013 to 2018. In total, 10,508 individuals without a history of HF in 2013 were included. Nighttime sleep duration, sleep restfulness and midday napping were self-reported. Logistic regression analyses were performed to examine the relationships between sleep problems and HF as well as falls, adjusting for covariates. A total of 313 (3.0%) participants reported HF, and 3899 (37.1%) experienced at least one fall event over the following 5-year period. Participants who had a short sleep duration (≤ 6) were more likely to report HF (OR = 1.27, 95% CI = 1.00-1.62) and falls (OR = 1.18, 95% CI = 1.07–1.30) than those who had a normal sleep duration (6–9 h) in the fully adjusted model. Participants having unrestful sleep were also more likely to report falls (OR = 1.23, 95% CI = 1.11–1.36) than those who had restful sleep. However, there was no significant association between midday napping and HF and falls. In conclusion, short sleep duration and sleep restfulness were independently associated with an increased risk of HF and falls, which may have important clinical and public health implications. Interventions to improve sleep quality may reduce the risk of HF and fall accidents among middle-aged and older people.

Examining Health Behaviors as Mechanisms Linking Earlier Pubertal Timing with Accelerated Epigenetic Aging in Late Adolescence

Article

Full-text available

Oct 2024
J YOUTH ADOLESCENCE

Earlier pubertal timing is associated with accelerated epigenetic aging, but the underlying mechanisms are not well understood. This three-wave longitudinal study examined negative health behaviors, specifically substance use, short sleep duration, and poor diet quality in middle adolescence, as mediators of links between earlier phenotypic and perceived pubertal timing measured in early adolescence and epigenetic aging on three epigenetic clocks in late adolescence (GrimAge, DunedinPACE, and PhenoAge). Phenotypic pubertal timing measured physical pubertal maturation relative to chronological age, whereas perceived pubertal timing was based on adolescents’ subjective interpretation of their pubertal timing relative to their peers. Participants included 1213 youth (51% female, 49% male; 62% Black, 34% White) who participated during early adolescence (mean age = 13.10 years), middle adolescence (mean age = 16.1 years) and late adolescence (mean age = 19.7 years). Results from a mediation model revealed a mediation effect of earlier phenotypic pubertal timing on accelerated GrimAge in late adolescence through higher substance use during middle adolescence. There was also a direct effect of earlier phenotypic pubertal timing on accelerated DunedinPACE in males. Sleep duration and diet quality did not emerge as mediators but shorter sleep duration predicted accelerated GrimAge in females. These findings suggest that higher substance use presents a mechanism through which earlier maturing youth experience faster epigenetic aging that puts them at risk for poorer health across the lifespan.

Getting Up Early as Practiced in Islam and the Scientific Response of Our Bodies:

Article

Full-text available

Sep 2024

The Quran has a lot of verses where Allah (S.W.T.) states that day is for work and night is for relaxation. Furthermore, Hadiths indicate that as Allah is the sole one who created the cosmos and humanity, He is aware of what is best for them and how they should live. Everything that Allah says in the Quran is good for all of humanity. Comparing it to human physiology, we uncover an abundance of further data demonstrating the detrimental effects of disrupting routine against the cycle mentioned in the Quran and Sunnah. In the current review, we have compiled verses from the Quran and the Sunnah to illustrate how the body responds to early wakefulness. We have also used scientific evidence in our research. One can learn about the beneficial and dangerous consequences of early and late wakefulness on the human body by reading the complete article.

Major risks of harmful environmental carcinogenic effects in light industry enterprises

Article

Full-text available

Jun 2024

Anatolie Baciu

Synthesis paper revealing fundamental data on the epigenetic determination of the initiation and maintenance of neoplastic processes in the breast tissue of female workers in light industry enterprises. The primary importance of the synchronization of circadian rhythms in the environment and the biorhythms of the biological molecular, cellular and internal tissue clocks is noted. Preventive programs should be based on preventing the desynchronization of neuroendocrine mechanisms involving melatonin and hormone-dependent tissues of the internal environment with circadian light/dark cycles of the external environment. The forced nature of the work activity associated with the development of social jetlag requires the provision of recreation periods after the rotation period.

Investigating the methods and health outcomes of research studies on light pollution and human physiology and behaviour: a systematic review

Conference Paper

Jun 2022

Light at night (LAN) enables humans to extend their lifestyle and exploration, cultivates economic growth, and increases the perception of safety. On the other hand, LAN has been connected to adverse health outcomes, such as circadian disruption, mood effects, and increased breast cancer incidence risk in humans. Studies investigating health outcomes of LAN utilize a variety of methods sometimes resulting in conflicting outcomes. We conducted a systematic review focusing on the experimental methods and health outcomes of LAN studies. While most studies found a negative impact of LAN on human health, lighting conditions were not adequately reported or controlled in many cases. Recommendations are provided for future research studies investigating LAN effects on human health outcomes.

Anthropogenic disturbance affects calling and collective behaviour in corvid roosts

Article

Full-text available

May 2024
PHILOS T R SOC B

Acoustic communication plays an important role in coordinating group dynamics and collective movements across a range of taxa. However, anthropogenic disturbance can inhibit the production or reception of acoustic signals. Here, we investigate the effects of noise and light pollution on the calling and collective behaviour of wild jackdaws (Corvus monedula), a highly social corvid species that uses vocalizations to coordinate collective movements at winter roosting sites. Using audio and video monitoring of roosts in areas with differing degrees of urbanization, we evaluate the influence of anthropogenic disturbance on vocalizations and collective movements. We found that when levels of background noise were higher, jackdaws took longer to settle following arrival at the roost in the evening and also called more during the night, suggesting that human disturbance may cause sleep disruption. High levels of overnight calling were, in turn, linked to disruption of vocal consensus decision-making and less cohesive group departures in the morning. These results raise the possibility that, by affecting cognitive and perceptual processes, human activities may interfere with animals’ ability to coordinate collective behaviour. Understanding links between anthropogenic disturbance, communication, cognition and collective behaviour must be an important research priority in our increasingly urbanized world. This article is part of the theme issue ‘The power of sound: unravelling how acoustic communication shapes group dynamics’.

Random forest regression exploring contributing factors to artificial night-time lights observed in VIIRS satellite imagery

Article

Full-text available

Mar 2024

Artificial night-time lights (ANTL) pose environmental, economic, and social problems. To effectively manage this issue, it is important to understand the sources that contribute to it. Previous research has presented conflicting views on the relative importance of streetlamps and spill-over light from buildings as contributors to ANTL. In this study, we used satellite images, ground surveys of streetlamps and buildings in the city of Hobart, Tasmania, Australia, to determine the major contributing sources of ANTL. Imagery from the Visible Infrared Imaging Radiometer Suite (VIIRS) satellite was used to map ANTL. We developed a predictive random forest regression (RFR) model and found that streetlamps were the major contributor, followed by the building footprint area. We also found that an increase in both the number of streetlamps and buildings leads to an increase in ANTL observable in VIIRS satellite data. The RFR model performed well with an R² of 0.94 and a median normalised root mean square error of 6.25%.

Association between sleep duration, depression and breast cancer in the United States: a national health and nutrition examination survey analysis 2009–2018

Article

Full-text available

Feb 2024

Objective Breast cancer is the most common cancer in women, threatening both physical and mental health. The epidemiological evidence for association between sleep duration, depression and breast cancer is inconsistent. The aim of this study was to determine the association between them and build machine-learning algorithms to predict breast cancer. Methods A total of 1,789 participants from the National Health and Nutrition Examination Survey (NHANES) were included in the study, and 263 breast cancer patients were identified. Sleep duration was collected using a standardized questionnaire, and the Nine-item Patient Health Questionnaire (PHQ-9) was used to assess depression. Logistic regression yielded multivariable-adjusted breast cancer odds ratios (OR) and 95% confidence intervals (CI) for sleep duration and depression. Then, six machine learning algorithms, including AdaBoost, random forest, Boost tree, artificial neural network, limit gradient enhancement and support vector machine, were used to predict the development of breast cancer and find out the best algorithm. Results Body mass index (BMI), race and smoking were statistically different between breast cancer and non-breast cancer groups. Participants with depression were associated with breast cancer (OR = 1.99, 95%CI: 1.55–3.51). Compared with 7–9h of sleep, the ORs for <7 and >9 h of sleep were 1.25 (95% CI: 0.85–1.37) and 1.05 (95% CI: 0.95–1.15), respectively. The AdaBoost model outperformed other machine learning algorithms and predicted well for breast cancer, with an area under curve (AUC) of 0.84 (95%CI: 0.81–0.87). Conclusions No significant association was observed between sleep duration and breast cancer, and participants with depression were associated with an increased risk for breast cancer. This finding provides new clues into the relationship between breast cancer and depression and sleep duration, and provides potential evidence for subsequent studies of pathological mechanisms.

Association between night work and prostate cancer: a systematic review and meta‑analysis

Article

Full-text available

Jan 2024
INT ARCH OCC ENV HEA

Objective The aim was to conduct a systematic review and meta-analysis to study the association between night work and the development of prostate cancer. Methods A systematic literature search was conducted in CINAHL, Embase, MEDLINE, and Web of Science. Studies were included based on a PECOS; the population included men in/above the working age, exposure defined as night work, outcome defined as prostate cancer, and study design restricted to cohort studies. The exclusion of articles, risk-of-bias assessment, and data extraction were performed by two reviewers. A meta-analysis was conducted using a random-effects model, including a sensitivity analysis stratified based on the risk-of-bias assessment. We evaluated publication bias using a funnel plot and Egger´s test, and the level of evidence was assessed using GRADE. Results A total of 528 articles were identified, and eight cohort studies were included. Three studies had a moderate risk of bias, while five studies had a high risk of bias. The meta-analysis showed a pooled hazard ratio (HR) of 1.0 (95% CI 0.6–1.7). In the sensitivity analysis, moderate vs. high risk-of-bias studies showed a pooled HR of 1.2 (95% CI 0.3–4.1) and 0.9 (95% CI 0.6–1.3), respectively. Based on GRADE, the level of evidence was rated low. Conclusion We found no association between night work and the development of prostate cancer. The evidence was assessed as limited and inconsistent. Future studies encompassing consistent definitions of night work, including objective exposure data, are highly warranted.

Actigraphy-derived measures of sleep and risk of prostate cancer in the UK Biobank

Article

Nov 2023
J NATL CANCER I

Background Studies of sleep and prostate cancer are almost entirely based on self-report, with limited research using actigraphy. Our goal was to evaluate actigraphy-measured sleep and prostate cancer and to expand on findings from prior studies of self-reported sleep. Methods We prospectively examined 34 260 men without a history of prostate cancer in the UK Biobank. Sleep characteristics were measured over 7 days using actigraphy. We calculated sleep duration, onset, midpoint, wake-up time, social jetlag (difference in weekend-weekday sleep midpoints), sleep efficiency (percentage of time spent asleep between onset and wake-up time), and wakefulness after sleep onset. Cox proportional hazards models were used to estimate covariate-adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). Results Over 7.6 years, 1152 men were diagnosed with prostate cancer. Sleep duration was not associated with prostate cancer risk. Sleep midpoint earlier than 4:00 am was not associated with prostate cancer risk, though sleep midpoint of 5:00 am or later was suggestively associated with lower prostate cancer risk but had limited precision (earlier than 4:00 am vs 4:00-4:59 am HR = 1.00, 95% CI = 0.87 to 1.16; 5:00 am or later vs 4:00-4:59 am HR = 0.79, 95% CI = 0.57 to 1.10). Social jetlag was not associated with greater prostate cancer risk (1 to <2 hours vs <1 hour HR = 1.06, 95% CI = 0.89 to 1.25; ≥2 hours vs <1 hour HR = 0.90, 95% CI = 0.65 to 1.26). Compared with men who averaged less than 30 minutes of wakefulness after sleep onset per day, men with 60 minutes or more had a higher risk of prostate cancer (HR = 1.20, 95% CI = 1.00 to 1.43). Conclusions Of the sleep characteristics studied, higher wakefulness after sleep onset—a measure of poor sleep quality—was associated with greater prostate cancer risk. Replication of our findings between wakefulness after sleep onset and prostate cancer are warranted.

The effect of nutrition and physical activity on sleep quality among adults: a scoping review

Article

Full-text available

Oct 2023

Sleep quality and its effects have become a public concern over the last few years. While the prevalence of sleep disorders was increasing, several studies have linked diet and physical activity as a cause of it. Indeed, many people complain about their sleeping problems without considering their lifestyle as a cause. This leads the efforts to focus on these principal factors and find their specific effect. The study aims to map out the research on the effect of nutrition and physical activity on sleep quality. The literature search was conducted in electronic libraries and databases related to nutrition and medical literature – Google Scholar, PubMed, and ScienceDirect– using relevant selected keywords. Article inclusion and selection were made by excluding duplicates, analyzing titles and abstracts, and reviewing the articles’ full text. This review included 61 articles. This literature study reinforces the importance of researching sleep and the lifestyle contributors to poor sleep, such as physical activity and nutrition.

Exposure to polycyclic aromatic hydrocarbons increases the risk of poor sleep pattern in US adults: results from the NHANES (2005–2010)

Article

Full-text available

Oct 2023
ENVIRON SCI POLLUT R

Recently, polycyclic aromatic hydrocarbons (PAHs) were found to be linked to various diseases. The current study’s objective was to explore whether or not there was a relation between PAH exposure and poor sleep pattern. We evaluated nine urine PAH metabolites as exposures in our cross-sectional research based on the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. Logistic regression, restricted cubic spline regression (RCS) model, weighted quantile sum (WQS) regression, subgroup analysis, and mediation analysis were used to assess the associations between PAH metabolism and poor sleep pattern risk. After controlling for all confounding variables, several primary PAH metabolites, namely 1-hydroxynapthalene (1-NAP, OR 1.32, 95% CI 1.04–1.68), 2-hydroxyfluorene (2-FLU, OR 1.34, 95% CI 1.05–1.71), 1-hydroxyphenanthrene (1-PHE, OR 1.30, 95% CI 1.03–1.64), 9-hydroxyfluorene (9-FLU, OR 1.38, 95% CI 1.09–1.74), and ∑PAHs (OR 1.33, 95% CI 1.05–1.69), compared to the bottom tertile, were associated with increased risk of poor sleep pattern. The WQS regression analysis showed that 9-FLU and 1-NAP comprised the two most important factors related to poor sleep pattern. Mediation analysis revealed that inflammation acted as a mediator between PAHs and the prevalence of poor sleep pattern. In conclusion, exposure to PAHs may be associated with poor sleep pattern. Inflammation is a mediator of the effects of PAH exposure on poor sleep pattern.

Poor sleep behaviors and high genetic susceptibility increase the risk of osteoarthritis

Preprint

Full-text available

Sep 2023

Background Emerging research evidence suggests an association between sleep behaviors and the risk of osteoarthritis. The various sleep behaviors are typically correlated; however, most previous studies have focused on a particular sleep behavior without considering the overall sleep pattern. Combining conventional evidence from UK Biobank longitudinal data and genetic evidence from Mendelian randomization methods to infer causality between sleep behaviors and osteoarthritis (OA) at different sites. Method First, we conducted an assessment of the association between various sleep behaviors and different OA sites based on the comprehensive prospective cohort study of the UK Biobank. Furthermore, we constructed individual sleep risk scores (ISRS) to evaluate their effect on OA when combined. Second, we utilized MR to provide genetic evidence for the causal linkage between sleep behavior and OA. Finally, we calculated a genetic risk score (GRS) for OA based on a large-scale genome-wide association study and assessed the joint effect of sleep and genetic factors on the risk of OA. Results We found a U-shaped relationship between sleep duration and the risk of OA (Pnonlinear < 0.001), with the lowest risk for sleep duration of 7–8 hours per day. Participants with often and sometimes insomnia had a 46.9% and 16.4% increased risk of OA (HR Sometimes = 1.164, 95% CI = 1.132∼1.197, PSometimes = 3.44×10− 26; HR Usually =1.469, 95% CI = 1.426∼1.514, PUsually =3.82×10− 142), respectively, while MR analysis also provided consistent evidence. Similar results were observed in participants who were daytime dozing, but no association between daytime dozing and risk of OA was shown in the MR analysis. In observational studies, snoring and difficulty getting up are associated with an increased risk of OA. We further constructed ISRS with potential risk sleep factors. We found that the risk of OA was positively associated with ISRS; furthermore, if all participants maintained healthy sleep behavior, 21.3% of OA cases could be removed. Conclusion Unhealthy sleep behaviors, individually or in combination, could increase the risk of OA, while poor sleep behaviors and genetic factors can collaboratively increase the risk of OA.

Association of habitual sleep duration and its trajectory with the risk of cancer according to sex and body mass index in a population‐based cohort

Article

Full-text available

Jul 2023
CANCER-AM CANCER SOC

Background The relationship between sleep duration and cancer in China remains inconclusive. The authors investigated the association between sleep duration and cancer from both static and dynamic perspectives. Methods This study was based on the China Health and Retirement Longitudinal Study. We first tested the hazard ratios (HRs) with 95% confidence intervals (CIs) between baseline sleep duration and incident cancer using Cox proportional hazards regression analysis. Sleep duration trajectories from 2011 to 2015 were identified using group‐based trajectory modeling to examine the subsequent risk of incident cancer from 2015 to 2018 using Cox proportional hazards regression model. Results The risk of incident cancer increased by 69% (HR, 1.69; 95% CI, 1.19–2.39) in individuals who slept for <7 h per day (vs. 7 to ≤8 h), 41% (HR, 1.41; 95% CI, 1.01–1.95) in those who slept for <6 h per night (vs. 6 to ≤8 h), and 60% (HR, 1.60; 95% CI, 1.01–2.55) in those who did not take any naps during the day (vs. >60 min). Stratified by sex and body mass index, the risk of cancer was evident among women with night sleep of <6 h (vs. 6–8 h). However, the duration of <7 h of total sleep among men and overweight individuals was associated with cancer risk. Moreover, individuals with a short night sleep duration but no napping had a higher risk of cancer. Furthermore, cancer risk was only observed in individuals with short stable trajectory of night sleep (HR, 2.01; 95% CI, 1.07–3.80) and among women with short stable trajectory of total sleep (HR, 2.26; 95% CI, 1.13–4.52). Conclusions Cancer incidence risk was observed in participants with sleep duration of <7 h and among women with short stable sleep trajectory. Short nights and total sleep duration were both associated with a high risk of incident cancer, but varied by sex. Interestingly, cancer risk was restricted to women with short stable sleep trajectory. Plain Language Summary This study showed that short nights and total sleep duration were associated with a high risk of cancer incidence in middle‐aged and elderly Chinese population, with implications for early effective cancer prevention. Habitual sleep is a modifiable and dynamic lifestyle behavior, and long‐term short sleep trajectories among women can predict cancer outcomes. Future studies should examine the association between the trajectory of sleep parameters based on objective measures and specific cancer types.

Mobile sensing to advance tumor modeling in cancer patients: A conceptual framework

Article

Full-text available

Jul 2023

As mobile and wearable devices continue to grow in popularity, there is strong yet unrealized potential to harness people's mobile sensing data to improve our understanding of their cellular and biologically-based diseases. Breakthrough technical innovations in tumor modeling, such as the three dimensional tumor microenvironment system (TMES), allow researchers to study the behavior of tumor cells in a controlled environment that closely mimics the human body. Although patients' health behaviors are known to impact their tumor growth through circulating hormones (cortisol, melatonin), capturing this process is a challenge to rendering realistic tumor models in the TMES or similar tumor modeling systems. The goal of this paper is to propose a conceptual framework that unifies researchers from digital health, data science, oncology, and cellular signaling, in a common cause to improve cancer patients' treatment outcomes through mobile sensing. In support of our framework, existing studies indicate that it is feasible to use people's mobile sensing data to approximate their underlying hormone levels. Further, it was found that when cortisol is cycled through the TMES based on actual patients' cortisol levels, there is a significant increase in pancreatic tumor cell growth compared to when cortisol levels are at normal healthy levels. Taken together, findings from these studies indicate that continuous monitoring of people's hormone levels through mobile sensing may improve experimentation in the TMES, by informing how hormones should be introduced. We hope our framework inspires digital health researchers in the psychosocial sciences to consider how their expertise can be applied to advancing outcomes across levels of inquiry, from behavioral to cellular.

Enhancing the Sustainability of Outdoor Floodlighting for Cultural Heritage Buildings

Conference Paper

Full-text available

Jun 2023

Transcriptomic dysregulation in zebrafish brain exposed to artificial light at night: a comprehensive analysis of gene expression and pathway alterations

Article

Feb 2025
BIOL RHYTHM RES

Joint association of sleep patterns and oxidative balance score with all-cause and cardiovascular mortality among the general population

Article

Full-text available

Jan 2025

Background This study investigates the joint effect of sleep patterns and oxidative balance score (OBS) on all-cause and CVD mortality in the general population. Methods We examined 21,427 individuals aged 18–85 from NHANES 2005–2014, connecting them to mortality data until December 31, 2019, using interview and physical examination dates. Surveys collected data on sleep duration, self-reported sleep disturbance, and doctor-told sleep disorders, classified into healthy, intermediate, and unhealthy sleep patterns. OBS was calculated based on twenty oxidative stress-related exposures to dietary and lifestyle factors. Cox proportional hazards model was conducted to evaluate the association between sleep patterns or OBS alone and combined with all-cause and CVD mortality. Results Poor sleep patterns and pro-oxidant OBS (Q1 & Q2) were identified as risk factors for mortality. Each point increase in OBS was associated with a 3% decrease in both all-cause mortality and CVD mortality. There was an interaction between sleep patterns and OBS (P for interaction = 0.013). Joint analyses revealed that participants with combined unhealthy (intermediate and poor) sleep pattern and pro-oxidant OBS were significantly associated with increased risk of all-cause (HR = 1.45 [1.21–1.74]) and CVD mortality (HR = 1.60 [1.12–2.28]). Furthermore, stratified analysis highlighted that this joint effect was more prominent among individuals without hypertension or diabetes; more notable for all-cause mortality in younger individuals and for CVD mortality in the elderly. Conclusion We identified a significant interaction between sleep patterns and OBS affecting all-cause mortality. Unhealthy sleep patterns and pro-oxidant OBS were jointly and positively associated with an increased risk of all-cause and CVD mortality. Interventions targeting healthy sleep patterns and antioxidant lifestyles may promote health outcomes.

Genetic and epigenetic alterations in night shift nurses with breast cancer: a narrative review

Article

Full-text available

Jan 2025
Canc Cell Int

This narrative review explores the link between breast cancer and night shift work in nurses, focusing on genetic and epigenetic factors. Breast cancer disproportionately affects women globally, and night shift work is increasingly recognized as a potential risk factor. Nurses who work consecutive overnight shifts face elevated risks due to disruptions in their circadian rhythms. Studies suggest that working six or more successive night shifts, particularly over five years or more, may increase breast cancer risk. This review hypothesizes that disruptions in the sleep-wake cycle, such as changes in melatonin production and telomere length, could contribute to breast cancer susceptibility. Currently, there is limited genetic evidence to support this hypothesis. However, it is plausible that genetic and epigenetic alterations, including changes in genes like ER and HER2, may heighten the risk for night shift nurses. These alterations may involve variations in telomere length, DNA methylation, and disruptions in critical breast cancer-related genes. We highlight various genetic and epigenetic changes that may influence this increased susceptibility. Further research is needed to explore the underlying mechanisms and contributing factors in this association.

Horaires postés et santé

Article

Jan 2015

Influence of melatonin supplementation on cancer-related fatigue: a meta-analysis of randomized controlled trials

Article

Dec 2024
CLIN TRANSL ONCOL

Previous studies that evaluated the influence of melatonin supplementation on cancer-related fatigue (CRF) revealed inconsistent results. The present meta-analysis was performed to systematically evaluate the influence of melatonin on the severity of fatigue in patients with cancer. Relevant randomized controlled trials (RCTs) were acquired by conducting a comprehensive search in the PubMed, Embase, and Cochrane Library databases. Only RCTs published as full-length English-language articles were included. A random-effects model was utilized to combine the findings by incorporating its potential influence. Nine RCTs were included for the meta-analysis. Compared to the placebo, melatonin supplementation improved the symptoms of fatigue of these patients (standardized mean difference [SMD]: −0.23, 95% confidence interval [CI]: −0.44 to −0.01, p = 0.04, I2 = 53%). The univariate analysis suggested that the treatment duration was significantly correlated with the improvement of melatonin supplementation on CRF (coefficient = −0.0063, p = 0.02), which largely explains the source of heterogeneity (adjusted R2 = 83.7%). The subgroup analysis revealed significantly improved fatigue in studies with treatment durations of ≥13 weeks, but not in studies with treatment durations of <13 weeks (SMD: −0.38 vs. 0.06, p for subgroup difference = 0.02). The further subgroup analysis suggested that the results were not significantly influenced by the type of cancer, status (advanced cancer or overall cancer), sample size, treatment (active anticancer treatment or palliative care only), dose of melatonin, or scale for evaluating fatigue symptoms. Melatonin supplementation may relieve CRF, especially for intervention durations of ≥13 weeks.

Sleep Disorders and Oncological Diseases

Article

Nov 2024
Neurosci Behav Physiol

Night shift work and breast cancer risk – 2023 update of epidemiologic evidence

Article

Full-text available

Sep 2024

Introduction Night shift work is a complex and frequent occupational exposure, and breast cancer stands as the most prevalent cancer in women. The International Agency for Research on Cancer (IARC) has twice classified night shift work as a probable breast carcinogen, with the latest classification in June 2019. Since that time, new epidemiologic data has emerged. Methods We searched PubMed for original articles based on cohort and case-control studies of “breast cancer and night shift work” published after the IARC evaluation in June 2019. Results In total six cohorts and four case-control studies were included in our review. Overall, we observed some support for associations between persistent (long duration or high frequency) night shift work and an increase in breast cancer risk, though most studies were relatively small and statistically under-powered. Moreover, the recent studies do not contribute further evidence regarding the interaction with menopausal status, diurnal preference, hormonal subtypes of breast cancer or gene-environment aspects, which were issues that were left from the IARC evaluation. Conclusions The available new results somewhat consolidate the epidemiological evidence from IARC's 2019 evaluation, and do not provide further evidence regarding interaction of interest, e.g. menopausal status, etc. Therefore, long term follow-up of prospective cohorts or nested case-control studies, including precise exposure assessment and examinations of relevant interactions such as menopausal status, diurnal preference, hormonal subtypes of breast cancer and gene-environment aspects, are warranted. Meanwhile, protective measures for the night workers should be considered.

Sleep and Immune System Crosstalk: Implications for Inflammatory Homeostasis and Disease Pathogenesis

Article

Full-text available

Sep 2024

Background Sleep and immune function are interconnected aspects of health that mutually impact each other in disease development and inflammatory homeostasis. Different aspects of immunology are regulated by different sleep characteristics, impacting on specific aspects of immune function including cytokine production and T-cell activity. Ongoing disruptions of sleep have been linked to heightened inflammation and are suspected in the pathogenesis and disease course of a range of life-style-related illnesses, including diabetes and neurodegenerative diseases. Summary This review provides a comprehensive overview of knowledge on the interaction of sleep with the immune system, its modulation of inflammatory balance, and the pathogenesis of many diseases. It emphasizes how sleep deficiency compromises immune function by means of a systemic, low-grade inflammatory response, while adequate sleep promotes intense immune responses and thus enables efficient pathogen clearance and the maintenance of immune memory. The mutual influence of sleep on the immune system underlines its critical involvement in health preservation and the course of disease. Key Message Sleep plays an indispensable role in immune health, mediating the efficiency of immune responses and the course of the regulation of inflammation. Chronic sleep deprivation can result in a low-grade inflammation that substantially contributes to the onset and exacerbation of metabolic and neurodegenerative disorders. The intimate linkage between sleep and immune function can be one strategic approach to therapy, improving health outcomes by leveraging this sleep-immune connection.

Sleep Inertia and Its Associates in Shift and Non-Shift Workers

Article

Aug 2024

Objective We investigated the difference in sleep inertia between shift workers (SWs) and non-shift workers (NSWs) and the effects of depressive symptoms, sleepiness, insomnia, and chronotype on sleep inertia in SWs and NSWs.Methods Altogether, 4,561 SWs (2,142 men and 2,419 women, aged 36.99±9.84 years) and 2,093 NSWs (999 men and 1,094 women, aged 37.80±9.73 years) participated in the current study. All participants completed the Sleep Inertia Questionnaire (SIQ), Epidemiological Studies Depression Scale (CESD), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and Morningness–Eveningness Questionnaire (MEQ) through an online survey.Results SWs reported higher SIQ scores than NSWs after controlling for CESD, ESS, ISI, or MEQ. The CESD, ESS, ISI, and MEQ predicted SIQ in both SWs and NSWs. The effects of CESD and MEQ on SIQ were stronger in SWs and NSWs, respectively. The indirect effects of CESD and MEQ on SIQ via ESS were significantly moderated by work schedules.Conclusion SWs showed higher sleep inertia than NSWs. The effect of chronotypes on sleep inertia was more prominent in NSWs than in SWs. However, the effect of depressive symptoms on sleep inertia was more prominent in SWs than in NSWs. Moreover, the effect of depressive symptoms or chronotypes on sleep inertia was mediated by sleepiness, and such indirect effects were significantly different among the participants stratified by work schedules.

Sleep disorders and oncological diseases

Article

Jan 2024
ZH NEVROL PSIKHIATR

The study of neurological symptoms and signs connected with neoplasms and antitumor therapy is relevant in the context of an increasing prevalence of cancer. The COVID-19 pandemic and social factors have increased the number of patients suffering from insomnia. Sleep disorders is an unfavorable prognostic factor for neoplasms. The review presents risk factors and mechanisms of sleep disturbance, their relationship with inflammation and dysfunction of the immune system in cancer. In particular, dysfunction of the melatonergic system is discussed as a risk factor for the development of insomnia and cancer. The relevance of developing measures aimed at the rehabilitation of patients in order to restore normal sleep, which plays a fundamental role in maintaining a person's mental and physical health, is emphasized.

Impacts of Static Lighting in Confined Spaces on the Circadian Parameters, Alertness, Performance and Well-Being

Article

Full-text available

Apr 2024

The static lighting condition (SLC) in confined spaces may pose great challenges to the health of long-stay workers, inducing sleep disorders, cognitive decline, and negative emotions such as depression or anxiety. To explore human responses to the SLC (300 lx and 6000 K), 20 young subjects (22.6 ± 1.88 years old) were recruited in the underground confined lab for a week by measuring melatonin, core body temperature (CBT), subjective alertness (KSS score), sleep quality (Pittsburgh Sleep Quality Index, PSQI), Psychomotor Vigilance Task (PVT), Hamilton Depression Scale (HAMD) and Self-rating Anxiety Scale (SAS). The results showed a posterior shift in circadian rhythm after 1 week of confinement, with 0.62 h delay of dim light melatonin onset (DLMO), higher melatonin concentrations in the evening, lower melatonin concentrations at midnight, a day-by-day increase in KSS and CBT at bedtime, but this decreased daily when waking up, with cumulative effects. There was a progressive increase in sleep latency, PSQI scores, response time and scores of subjective emotion scales, meaning worse sleep, performance and emotional state. Due to limited exposure to high-lighting stimuli during the daytime, the initial concentrations of melatonin increased in the evening and decreased before sleep. In confined spaces, active health interventions by dynamic lighting patterns were proposed to safeguard human health and performance.

No evidence linking sleep traits with white blood cell counts: Multivariable-adjusted and Mendelian randomization analyses

Article

Mar 2024
EUR J CLIN INVEST

Background Disturbances in habitual sleep have been associated with multiple age‐associated diseases. However, the biological mechanisms underpinning these associations remain largely unclear. We assessed the possible involvement of the circulating immune system by determining the associations between sleep traits and white blood cell counts using multivariable‐adjusted linear regression and Mendelian randomization. Methods Cross‐sectional multivariable‐adjusted linear regression analyses were done using participants within the normal range of total white blood cell counts (>4.5 × 10 ⁹ and <11.0 × 10 ⁹ /μL) from UK Biobank. For the sleep traits, we examined (short and long) sleep duration, chronotype, insomnia symptoms and daytime dozing. Two‐sample Mendelian randomization analyses were done using instruments for sleep traits derived from European‐ancestry participants from UK Biobank (over 410,000 participants) and using SNP‐outcome data derived from European‐ancestry participants from the Blood Cell Consortium ( N = 563,946) to which no data from UK Biobank contributed. Results Using data from 357,656 participants (mean [standard deviation] age: 56.5 [8.1] years, and 44.4% men), we did not find evidence that disturbances in any of the studied sleep traits were associated with differences in blood cell counts (total, lymphocytes, neutrophiles, eosinophiles and basophiles). Also, we did not find associations between disturbances in any of the studied sleep traits and white blood cell counts using Mendelian Randomization. Conclusion Based on the results from two different methodologies, disturbances in habitual sleep are unlikely to cause changes in blood cell counts and thereby differences in blood cell counts are unlikely to be underlying the observed sleep‐disease associations.

Eyes Wide Open: Sleep as a Potential Contributor to Racial and Ethnic Disparities in Cancer

Article

Jan 2024
CANCER EPIDEM BIOMAR

US racial and ethnic minoritized groups face disproportionate cancer burdens compared to White Americans. Investigating modifiable factors, such as sleep, that are socially patterned and inequitably distributed by race and ethnicity may advance understanding of cancer disparities and provide intervention opportunities. Emerging data suggest poor sleep health is associated with cancer. Yet, its contribution to racial and ethnic cancer disparities is understudied. In this narrative review, we explored the sleep-cancer relation through a disparities lens. We 1) summarized literature reporting on associations between sleep and cancer among racial and ethnic minority populations; 2) examined potential sleep-cancer mechanisms; and 3) discussed future directions. We identified five studies reporting on sleep-cancer associations among minoritized groups. Poor sleep health was associated with aggressive breast cancer among Black women, increased breast cancer risk among Asian women, and increased risk of breast and total cancer among Hispanic/Latinx Americans. Sleep and cancer disparities have similar socioeconomic and behavioral determinants, suggesting racial and ethnic minoritized groups may be vulnerable to poor sleep health and its adverse health impacts. Evidence indicates that the sleep-cancer disparities relation is an emerging, but important area of research that warrants further investigation, as sleep may be an avenue for reducing cancer disparities.

The effects of eye masks and earplugs on sleep quality, anxiety, fear, and vital signs in patients in an intensive care unit: A randomised controlled study

Article

Sep 2023
J SLEEP RES

In intensive care units, environmental factors like loud noises and bright lights can cause fear, anxiety, changes in vital signs, and sleep disturbances. The aim of this study was to find out how using earplugs and eye masks during the night affected sleep quality, anxiety, fear, and vital signs of patients in an intensive care unit. A total of 70 patients, 35 in the intervention and 35 in the control group, were included in this randomised controlled study. While the patients in the intervention group were provided with earplugs and eye masks for 3 nights in addition to their routine care, only routine care was given to the patients in the control group. The 'Introductory Information Form', 'Visual Analogue Scale-Fear (VAS-F)', 'Visual Analogue Scale-Anxiety (VAS-A)', 'Vital Signs Monitoring Form', and 'Richards-Campbell Sleep Questionnaire' were used for data collection. It was found that the mean scores of VAS-F, VAS-A, heart rate, diastolic and systolic blood pressure of the intervention group decreased significantly after the intervention, while their sleep quality increased significantly. In this study, it was found that using earplugs and eye masks for patients in an intensive care unit during the night was effective in improving patients' sleep quality and reducing fear, anxiety, and problems in vital signs.

Disrupted Sleep and Brain Functioning

Chapter

Aug 2023

Sleep is one of the most important aspects of the normal functioning of the brain and the entire organism. Research into the different ways in which sleep can be disrupted as well as the various consequences of sleep disruption have gained much attention recently. Here we explore the ways in which a single pathology (a malignant brain disease) can affect the sleeping patterns of a person. We also explore the various well-known consequences of sleep disruption, both local and systemic. Our goal is to show how this often overlooked pathology is crucial in the understanding of many common pathologies.KeywordsDisrupted sleepMalignant brain tumors

All-cause and major-cause mortality associated with sleep latency in the Korean Genome and Epidemiology Study (KoGES): a population-based prospective cohort study

Article

Jul 2023

Background: The all-cause and cause-specific mortality risk associated with sleep latencies in the general adult population is unknown. We aimed to investigate the association of habitual prolonged sleep latency with long-term all-cause and cause-specific mortality in adults. Methods: The Korean Genome and Epidemiology Study (KoGES) is a population-based prospective cohort study comprising community-dwelling men and women aged 40-69 years from Ansan, South Korea. The cohort was studied bi-annually from April 17, 2003, to Dec 15, 2020, and the current analysis included all individuals who completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire between April 17, 2003, and Feb 23, 2005. The final study population comprised 3757 participants. Data were analysed from Aug 1, 2021, to May 31, 2022. The main exposure was sleep latency groups based on the PSQI questionnaire: fell asleep in 15 min or less, fell asleep in 16-30 min, occasional prolonged sleep latency (fell asleep in >30 min once or twice a week in the past month) and habitual prolonged sleep latency (fell asleep in >60 min more than once a week or fell asleep in >30 min ≥3 times a week, or both) in the past month at baseline. Outcomes were all-cause and cause-specific (cancer, cardiovascular disease, and other causes) mortality reported during the 18-year study period. Cox proportional hazards regression models were used to examine the prospective relationship between sleep latency and all-cause mortality, and competing risk analyses were done to investigate the association of sleep latency with cause-specific mortality. Findings: During a median follow-up of 16·7 years (IQR 16·3-17·4), 226 deaths were reported. After adjusting for demographic characteristics, physical characteristics, lifestyle factors, chronic conditions, and sleep variables, self-reported habitual prolonged sleep latency was associated with an increased risk of all-cause mortality (hazard ratio [HR] 2·22, 95% CI 1·38-3·57) compared to the reference group (those who fell asleep in 16-30 min). In the fully adjusted model, habitual prolonged sleep latency was associated with a more than doubled risk of dying from cancer compared to the reference group (HR 2·74, 95% CI 1·29-5·82). No significant association was observed between habitual prolonged sleep latency and deaths from cardiovascular disease and other causes. Interpretation: In this population-based prospective cohort study, habitual prolonged sleep latency was independently associated with an increased risk of all-cause and cancer-specific mortality in adults (independently of demographic characteristics, lifestyle factors, chronic morbidities, and other sleep variables). Although further studies are warranted to investigate the causality of the relationship, strategies or interventions to prevent habitual prolonged sleep latencies might enhance longevity in the general adult population. Funding: Korea Centers for Disease Control and Prevention.

Sleep and cancer recurrence and survival in patients with resected Stage III colon cancer: findings from CALGB/SWOG 80702 (Alliance)

Article

May 2023
BRIT J CANCER

Background: We sought to assess the influences of sleep duration, sleep adequacy, and daytime sleepiness on survival outcomes among Stage III colon cancer patients. Methods: We conducted a prospective observational study of 1175 Stage III colon cancer patients enrolled in the CALGB/SWOG 80702 randomised adjuvant chemotherapy trial who completed a self-reported questionnaire on dietary and lifestyle habits 14-16 months post-randomisation. The primary endpoint was disease-free survival (DFS), and secondary was overall survival (OS). Multivariate analyses were adjusted for baseline sociodemographic, clinical, dietary and lifestyle factors. Results: Patients sleeping ≥9 h-relative to 7 h-experienced a worse hazard ratio (HR) of 1.62 (95% confidence interval (CI), 1.01-2.58) for DFS. In addition, those sleeping the least (≤5 h) or the most (≥ 9 h) experienced worse HRs for OS of 2.14 (95% CI, 1.14-4.03) and 2.34 (95% CI, 1.26-4.33), respectively. Self-reported sleep adequacy and daytime sleepiness showed no significant correlations with outcomes. Conclusions: Among resected Stage III colon cancer patients who received uniform treatment and follow-up within a nationwide randomised clinical trial, very long and very short sleep durations were significantly associated with increased mortality. Interventions targeting optimising sleep health among indicated colon cancer patients may be an important method by which more comprehensive care can be delivered. Trial registration: ClinicalTrials.gov Identifier: NCT01150045.

Proteomic Research on the Therapeutic Properties of Medicinal Mushrooms

Chapter

Apr 2023

According to estimates, more than 800 mushroom species have been confirmed to possess various pharmacological properties. While the primary research focus has been on immunomodulatory and, more recently, on direct antitumor effects, many other therapeutic properties have also become important research subjects. Systems biology approaches, which include various omics methods coupled with bioinformatics, have begun to enter the field of medicinal mushroom research. Proteomics is a well-established hypothesis-generating discipline focused on the systemic study of proteins, used in discovering new pathways and processes resulting from physiological and pathological states or pharmacological interventions. It is particularly powerful in new potential therapeutic target discovery of “druggable proteins” or disease biomarkers of prognostic or therapeutic significance. Despite challenges in proteomics’ extensive data analysis and interpretation, proteomics remains indispensable for the detailed understanding and characterization of pharmacological effects.In comparison with genomics, proteomics generates more accurate data since several protein products may result from only one gene. This results from differential splicing and more than 200 posttranslational modifications, which affect protein function, stability, protein-protein, and other interactions. This chapter provides a current overview of proteomic research on medicinal mushrooms concerning anticancer, immunomodulatory, antidiabetic, hypolipidemic, antiatherosclerotic, hepatoprotective, and neuroprotective properties.KeywordsAnticancerAntidiabeticHepatoprotectiveHypolipidemicMedicinal mushroomsNeuroprotectiveProteomics

Brief Multimodal Intervention to Address Bedtime Procrastination and Sleep through Self-Compassion and Sleep Hygiene during Stressful Times

Preprint

Full-text available

Apr 2023

Bedtime procrastination is increasingly recognized as a widespread impediment to health-promoting sleep. Based on its potential malleability, bedtime procrastination is starting to be targeted for intervention using traditional health behavior models, but other cognitive and emotional factors that potentially modulate bedtime procrastination warrant more targeted intervention. The present research recruited college students (n = 93) with self-reported tendencies toward bedtime procrastination and low self-compassion early in the COVID-19 pandemic, and it examined a hybrid intervention model involving a single group meeting and home practices that focused on comprehensive sleep hygiene or intentional self-compassion practices, simultaneously leveraging social motivation and commitment. It also examined bedtime procrastination, sleep, emotion regulation, and procrastinatory cognitions. The study showed evidence for feasibility, acceptability, reduced bedtime procrastination, improved sleep, and moderated mediation whereby the relationship between increased self-compassion and decreased bedtime procrastination was mediated by improved emotion regulation for those with elevated reductions in procrastinatory cognition. Predictors of bedtime procrastination reduction and other relevant sequelae differed between self-compassion and sleep hygiene virtual trainings. Thus, the present research expands and synthesizes a burgeoning literature, suggesting that integrating effective elements into acceptable interventions may help reverse a cycle of self-criticism, emotion dysregulation, bedtime procrastination, and sleep-related difficulties for many who might benefit.

Sleep Deprivation Promotes Endothelial Inflammation and Atherogenesis by Reducing Exosomal miR-182-5p

Article

Apr 2023
ARTERIOSCL THROM VAS

Background: Insufficient or disrupted sleep increases the risk of cardiovascular disease, including atherosclerosis. However, we know little about the molecular mechanisms by which sleep modulates atherogenesis. This study aimed to explore the potential role of circulating exosomes in endothelial inflammation and atherogenesis under sleep deprivation status and the molecular mechanisms involved. Methods: Circulating exosomes were isolated from the plasma of volunteers with or without sleep deprivation and mice subjected to 12-week sleep deprivation or control littermates. miRNA array was performed to determine changes in miRNA expression in circulating exosomes. Results: Although the total circulating exosome levels did not change significantly, the isolated plasma exosomes from sleep-deprived mice or human were a potent inducer of endothelial inflammation and atherogenesis. Through profiling and functional analysis of the global microRNA in the exosomes, we found miR-182-5p is a key exosomal cargo that mediates the proinflammatory effects of exosomes by upregulation of MYD88 and activation of NF-ĸB/NLRP3 pathway in endothelial cells. Moreover, sleep deprivation or the reduction of melatonin directly decreased the synthesis of miR-182-5p and led to the accumulation of reactive oxygen species in small intestinal epithelium. Conclusions: The findings illustrate an important role for circulating exosomes in distant communications, suggesting a new mechanism underlying the link between sleep disorder and cardiovascular disease.

Long-term exposure to ambient air pollutants and their interaction with physical activity on insomnia: A prospective cohort study

Article

Feb 2023
ENVIRON RES

Exposure to air pollution or lack of physical activity (PA) increases the risk of insomnia. However, evidence on joint exposure to air pollutants is limited, and the interaction of joint air pollutants and PA on insomnia is unknown. This prospective cohort study included 40,315 participants with related data from the UK Biobank, which recruited participants from 2006 to 2010. Insomnia was assessed by self-reported symptoms. The annual average air pollutant concentrations of particulate matter (PM2.5, PM10), nitrogen oxides (NO2, NOX), sulfur dioxide (SO2) and carbon monoxide (CO) were calculated based on participants' addresses. We applied a weighted Cox regression model to evaluate the correlation between air pollutants and insomnia and newly proposed an air pollution score to assess joint air pollutants effect using a weighted concentration summation after obtaining the weights of each pollutant in the Weighted-quantile sum regression. With a median follow-up of 8.7 years, 8511 participants developed insomnia. For each 10 μg/m³ increase in NO2, NOX, PM10, SO2, the average hazard ratios (AHRs) and 95% confidence interval (CI) of insomnia were 1.10 (1.06, 1.14), 1.06 (1.04, 1.08), 1.35 (1.25, 1.45) and 2.58 (2.31, 2.89), respectively; For each 5 μg/m³ increase in PM2.5 and each 1 mg/m³ increase in CO, the corresponding AHRs (95%CI) were 1.27 (1.21, 1.34) and 1.83 (1.10, 3.04), respectively. The AHR (95%CI) for insomnia associated with per interquartile range (IQR) increase in air pollution scores were 1.20 (1.15, 1.23). In addition, potential interactions were examined by setting cross-product terms of air pollution score with PA in the models. We observed an interaction between air pollution scores and PA (P = 0.032). The associations between joint air pollutants and insomnia were attenuated among participants with higher PA. Our study provides evidence on developing strategies for improving healthy sleep by promoting PA and reducing air pollution.

Konservasi Air dan Energi dengan Menghidupkan Sunnah Nabi

Article

Sep 2013

Mujahidin Ahmad

em>Islam is a universal religion. Not only governs the relationship between servant and God but also regulates the relationship with fellow beings. Among the teachings of Islam that governs the relationship with the creatures is how the adherents of Islam set to be considerate of the environment, ie, how should humans maintain balance of nature and not ruin it. The use of water and energi, including matters governed by Islam through the Qur'an and the instructions Prophet Sallallaahu 'alaihi wasallam. Instructions regarding the procedure of which the Prophet made ablution, bathing, brushing teeth closely related to water conservation, while the doctrine of fasting, to walk to the mosque, turn off a light during sleep so strongly associated with the doctrine of the conservation of energy. By following the Sunnah of a Moslem not only to be rewarded, but also contribute to the conservation of natural resources whose benefits will be felt by all mankind</em

Rotating Night Shifts and Risk of Breast Cancer in Women Participating in the Nurses' Health Study

Article

Full-text available

Nov 2001

Background: Melatonin shows potential oncostatic action, and light exposure during night suppresses melatonin production. There is little information, however, about the direct effect of night work on the risk of cancer. We investigated the effect of night work in breast cancer. Methods: We examined the relationship between breast cancer and working on rotating night shifts during 10 years of follow-up in 78 562 women from the Nurses' Health Study. Information was ascertained in 1988 about the total number of years during which the nurses had worked rotating night shifts with at least three nights per month. From June 1988 through May 1998, we documented 2441 incident breast cancer cases. Logistic regression models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs), adjusted for confounding variables and breast cancer risk factors. All statistical tests were two-sided. Results: We observed a moderate increase in breast cancer risk among the women who worked 1-14 years or 15-29 years on rotating night shifts (multivariate adjusted RR = 1.08 [95% CI = 0.99 to 1.18] and RR = 1.08 [95% CI = 0.90 to 1.30], respectively). The risk was further increased among women who worked 30 or more years on the night shift (RR = 1.36; 95% CI = 1.04 to 1.78). The test for trend was statistically significant (P =.02). Conclusions: Women who work on rotating night shifts with at least three nights per month, in addition to days and evenings in that month, appear to have a moderately increased risk of breast cancer after extended periods of working rotating night shifts.

The 24‐Hour Sleep Propensity Function: Experimental Bases for Somnotypology

Article

Full-text available

Oct 1992

The present study investigated the temporal structure of sleep propensity during 48 hours using an ultrashort 7-min sleep/13-min wake cycle. Eight subjects were tested under two experimental conditions of either attempting sleep, or resisting sleep after a monitored night in the laboratory. Electrophysiological recordings were carried out during the 7-min trials. The temporal structure and the overall level of sleepiness of the 48-hour sleep propensity functions calculated from the amount of total sleep in each trial revealed a high within-subjects stability. This was found both across the two days of the study within conditions, and across conditions. Also, diurnal levels of sleepiness were systematically related to nocturnal sleep parameters. Subjects having short nocturnal sleep latencies and higher sleep efficiencies slept more during the day. It is proposed that the structure and level of the sleep propensity function can be used to characterize individuals along two dimensions of somnotypology: "morningness-eveningness" and "sleepy-alert."

Strogatz SH, Kronauer RE, Czeisler CA. Circadian pacemaker interferes with sleep onset at specific times each day: role in insomnia. Am J Physiol 253: R172-R178

Article

Full-text available

Aug 1987
Am J Physiol

The human circadian pacemaker modulates our desire and ability to fall asleep at different times of day. To study this circadian component of sleep tendency, we have analyzed the sleep-wake patterns recorded from 15 free-running subjects in whom the sleep-wake cycle spontaneously desynchronized from the circadian rhythm of body temperature. The analysis indicates that the distribution of sleep onsets during free run is bimodal, with one peak at the temperature trough and, contrary to previous reports, a second peak 9-10 h later. Furthermore, there are two consistent zones in the circadian temperature cycle during which normal subjects rarely fall asleep. We hypothesize that this bimodal rhythm of sleep tendency, revealed under free-running conditions, maintains the same fixed phase relation to the circadian temperature cycle during 24-h entrainment. This would imply that normally entrained individuals should experience a peak of sleep tendency in the midafternoon and a zone of minimal sleep tendency approximately 1-3 h before habitual bedtime. Our temporal isolation data thereby account quantitatively for the timing of the afternoon siesta and suggest that malfunctions of the phasing of the circadian pacemaker may underlie the insomnia associated with sleep-scheduling disorders.

Nocturnal eating and serum cholesterol of tree-shift workers

Article

Full-text available

Jan 1995

The goal of this study was to examine the effect of rotating three-shift work on the circadian distribution of dietary intake and to investigate the relationships between displaced eating and nutritional status variables [blood lipids, blood glucose, body mass index (BMI)]. Dietary data were collected by 147 replicate 24-h dietary recalls from 22 male industrial workers in rotating three-shift work. The intakes of energy and nutrients were estimated by the use of a nutrient data base. The BMI was calculated, and blood glucose, serum triglycerides, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol were measured once. The dietary intakes of energy, protein, total fat, saturated fat, total carbohydrates, sucrose, and dietary fiber did not differ between 24-h periods but did differ between work shifts and were lowest during the night. Correlation analyses between dietary intakes and nutritional status parameters showed that those who redistributed their eating most to the night shift had higher levels of serum total cholesterol and LDL and a higher LDL:HDL ratio; 63% of the LDL cholesterol level was explained by carbohydrate intake during night shifts. In contrast, the total intake for whole 24-h periods or across entire shift cycles was not related to serum variables or BMI. Dietary intake is lower during night shifts (34-37% of 24-h intake of various nutrients) than during morning shifts (43-47%) and afternoon shifts (47-59%). The redistribution of food intake to the night may be associated with metabolic disturbances in lipid metabolism.

Lucey DR, Clerici M, Shearer GMType 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev 9: 532-562

Article

Full-text available

Nov 1996

In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.

Nocturnal melatonin onset is phase locked to the primary sleep gate

Article

Full-text available

Aug 1997
Am J Physiol

In this study, we used the "ultrashort sleep-wake paradigm" (7/13), which measures sleep propensity three times an hour for 29 h, from 0700 to 1200 the next day, on 6 healthy male subjects concomitantly with melatonin plasma level. Melatonin was measured once an hour during the morning and early afternoon of the first day and three times an hour from 1600 to 1000 the following morning. Rectal temperature was measured continuously for four subjects. Subjects underwent the 7/13 paradigm three times, and in all three sessions consistent phase relationships were found between the nocturnal onset of melatonin secretion and opening of the nocturnal sleep gate; also, there was an inverse relationship between melatonin and core body temperature and an almost perfect out-of-phase relationship between sleep propensity and temperature, with the temperature peak falling precisely in the middle of the "forbidden zone" for sleep, i.e., the early evening nadir in sleepiness. On the basis of these phase relationships and previous findings from our laboratory on the effects of exogenous melatonin on the sleep propensity function, we conclude that melatonin participates in sleep-wake regulation in humans.

Humoral Regulation of Sleep

Article

Full-text available

Sep 1998
News Physiol Sci

Cytokines and hormones, including interleukin-1, tumor necrosis factor, growth hormone-releasing hormone, vasoactive intestinal polypeptide and prolactin, are involved in sleep regulation. These substances enhance sleep, inhibition of them inhibits sleep, and their brain levels vary with sleep. This knowledge helps our understanding of the humoral regulation of sleep.

Towards a unified model of neuroendocrine-immune interaction

Article

Full-text available

Sep 2001

Nikolai Petrovsky

Although the neuroendocrine system has immunomodulating potential, studies examining the relationship between stress, immunity and infection have, until recently, largely been the preserve of behavioural psychologists. Over the last decade, however, immunologists have begun to increasingly appreciate that neuroendocrine-immune interactions hold the key to understanding the complex behaviour of the immune system in vivo. The nervous, endocrine and immune systems communicate bidirectionally via shared messenger molecules variously called neurotransmitters, cytokines or hormones. Their classification as neurotransmitters, cytokines or hormones is more serendipity than a true reflection of their sphere of influence. Rather than these systems being discrete entities we would propose that they constitute, in reality, a single higher-order entity. This paper reviews current knowledge of neuroendocrine-immune interaction and uses the example of T-cell subset differentiation to show the previously under-appreciated importance of neuroendocrine influences in the regulation of immune function and, in particular, Th1/Th2 balance and diurnal variation there of.

Profile of 24-h Light Exposure and Circadian Phase of Melatonin Secretion in Night Workers

Article

Full-text available

Oct 2001
J BIOL RHYTHM

Light exposure was measured in 30 permanent night nurses to determine if specific light/dark profiles could be associated with a better circadian adaptation. Circadian adaptation was defined as a significant shift in the timing of the episode of melatonin secretion into the daytime. Light exposure was continuously recorded with ambulatory wrist monitors for 56 h, including 3 consecutive nights of work. Participants were then admitted to the laboratory for 24 h where urine was collected every 2 h under dim light for the determination of 6-sulphatoxymelatonin concentration. Cosinor analysis was used to estimate the phase position of the episode of melatonin secretion. Five participants showed a circadian adaptation by phase delay (“delayed participants”) and 3 participants showed a circadian adaptation by phase advance (“advanced participants”). The other 22 participants had a timing of melatonin secretion typical of day-oriented people (“nonshifters”). There was no significant difference between the 3 groups for total light exposure or for bright light exposure in the morning when traveling home. However, the 24-h profiles of light exposure were very distinctive. The timing of the main sleep episode was associated with the timing of light exposure. Delayed participants, however, slept in darker bedrooms, and this had a major impact on their profile of light/dark exposure. Delayed and advanced participants scored as evening and morning types, respectively, on a morningness-eveningness scale. This observation suggests that circadian phase prior to night work may contribute to the initial step toward circadian adaptation, later reinforced by specific patterns of light exposure.

Melatonin as a Chronobiotic / Anticancer Agent: Cellular, Biochemical, and Molecular Mechanisms of Action and their Implications for Circadian-Based Cancer Therapy

Article

Full-text available

Mar 2002

Melatonin, as a new member of an expanding group of regulatory factors that control cell proliferation and loss, is the only known chronobiotic, hormonal regulator of neoplastic cell growth. At physiological circulating concentrations, this indoleamine is cytostatic and inhibits cancer cell proliferation in vitro via specific cell cycle effects. At pharmacological concentrations, melatonin exhibits cytotoxic activity in cancer cells. At both physiological and pharmacological concentrations, melatonin acts as a differentiating agent in some cancer cells and lowers their invasive and metastatic status through alterations in adhesion molecules and maintenance of gap junctional intercellular communication. In other cancer cell types, melatonin, either alone or in combination with other agents, induces apoptotic cell death. Biochemical and molecular mechanisms of melatonin's oncostatic action may include regulation of estrogen receptor expression and transactivation, calcium/calmodulin activity, protein kinase C activity, cytoskeletal architecture and function, intracellular redox status, melatonin receptor-mediated signal transduction cascades, and fatty acid transport and metabolism. A major mechanism mediating melatonin's circadian stage-dependent tumor growth inhibitory action is the suppression of epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) activity. This occurs via melatonin receptor-mediated blockade of tumor linoleic acid uptake and its conversion to 13-hydroxyoctadecadienoic acid (13-HODE) which normally activates EGFR/MAPK mitogenic signaling. This represents a potentially unifying model for the chronobiological inhibitory regulation of cancer growth by melatonin in the maintenance of the host/cancer balance. It also provides the first biological explanation of melatonin-induced enhancement of the efficacy and reduced toxicity of chemo- and radiotherapy in cancer patients.

Metabolic Responses to Nocturnal Eating in Men Are Affected by Sources of Dietary Energy

Article

Full-text available

Aug 2002

Because night work is becoming more prevalent, we studied whether feeding at different times of a 24-h period would elicit different metabolic responses and whether dietary macronutrient composition would affect these responses. Seven men (26-43 y, 19.9-26.6 kg/m(2)) consumed two isocaloric diets, in a crossover design. The diets were a high carbohydrate (HC) diet [65 energy % (E%) carbohydrates, 20E% fat] and a high fat (HF) diet (40E% carbohydrates, 45E% fat). After a 6-d diet-adjustment period, the men were kept awake for 24 h and the food (continuation of respective diet) was provided as six isocaloric meals (i.e., every 4 h). Energy and substrate turnover, heart rate, mean arterial pressure (MAP), blood glucose, triacylglycerol (TAG), nonesterified fatty acid (NEFA) and glycerol were measured throughout the 24-h period. Significantly higher energy expenditure and NEFA concentration, and lower blood glucose and TAG concentrations were observed when the men consumed the HF diet than when they consumed the HC diet. Significant circadian patterns were seen in body and skin temperature (nadir, 0400-0500 h). When the men consumed the HF diet, significant circadian patterns were seen in fat oxidation (nadir, 0800-1200 h; plateau, 1200-0800 h), heat release (nadir, 0800-1200 h; plateau, 1600-0800 h), heart rate (nadir, 0000 h), blood glucose (nadir, 0800-1200 h; peak, 0000-0400 h), NEFA (nadir, 0800-1200 h; peak, 1200-2000 h) and TAG (nadir, 0800-1200 h; peak, 0400-0800 h) concentrations. Energy expenditure, carbohydrate oxidation, MAP and glycerol concentration did not display circadian patterns. Unequal variances eradicated most circadian effects in the HC-diet data. The increased TAG concentration in response to feeding at 0400 h might be involved in the higher TAG concentrations seen in shift workers. Distinct macronutrient/circadian-dependent postprandial responses were seen in most studied variables.

Health disorders of shift workers

Article

Full-text available

Apr 2003

Anders Knutsson

The effects of shift work on physiological function through disruption of circadian rhythms are well described. However, shift work can also be associated with specific pathological disorders. This article reviews the evidence for a relationship between specific medical disorders and working at night or on shift systems. The strongest evidence exists for an association with peptic ulcer disease, coronary heart disease and compromised pregnancy outcome.

Night-Shift Work and Risk of Colorectal Cancer in the Nurses’ Health Study

Article

Full-text available

Jul 2003
J NATL CANCER I

Exposure to light at night suppresses the physiologic production of melatonin, a hormone that has antiproliferative effects on intestinal cancers. Although observational studies have associated night-shift work with an increased risk of breast cancer, the effect of night-shift work on the risk of other cancers is not known. We prospectively examined the relationship between working rotating night shifts and the risk of colorectal cancers among female participants in the Nurses’ Health Study. We documented 602 incident cases of colorectal cancer among 78 586 women who were followed up from 1988 through 1998. Compared with women who never worked rotating night shifts, women who worked 1–14 years or 15 years or more on rotating night shifts had multivariate relative risks of colorectal cancer of 1.00 (95% confidence interval [CI] = 0.84 to 1.19) and 1.35 (95% CI = 1.03 to 1.77), respectively (Ptrend = .04). These data suggest that working a rotating night shift at least three nights per month for 15 or more years may increase the risk of colorectal cancer in women.

Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases.

Article

Oct 1996

Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases

Article

Oct 1996

McGraw-Hill Yearbook of Science and Technology

Article

Nov 1963
SOIL SCI

DAVID I. EGGENBERGER

Circadian pacemaker interferes with sleep onset at specific times each day: Role in insomnia

Article

Jan 1987
Am J Physiol

Melatonin: Nature’s most versatile biological signal?

Data

Apr 2014

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light ⁄ dark cycle via the suprachiasmatic nucleus. Pinealocytes function as ‘neuroendocrine transducers’ to secrete melatonin during the dark phase of the light ⁄ dark cycle and, consequently, melatonin is often called the ‘hormone of darkness’. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the ‘time of day’ and ‘time of year’ (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body’s chronological pacemaker or ‘Zeitgeber’. Synthesis of melatonin also occurs in other areas of the body, including the retina, the gastrointestinal tract, skin, bone marrow and in lymphocytes, from which it may influence other physiological functions through paracrine signaling. Melatonin has also been extracted from the seeds and leaves of a number of plants and its concentration in some of this material is several orders of magnitude higher than its night-time plasma value in humans. Melatonin participates in diverse physiological functions. In addition to its timekeeping functions, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect which it exerts even during ischemia. Melatonin’s cytoprotective properties have practical implications in the treatment of neurodegenerative diseases. Melatonin also has immuneenhancing and oncostatic properties. Its ‘chronobiotic’ properties have been shown to have value in treating various circadian rhythm sleep disorders, such as jet lag or shift-work sleep disorder. Melatonin acting as an ‘internal sleep facilitator’ promotes sleep, and melatonin’s sleep-facilitating properties have been found to be useful for treating insomnia symptoms in elderly and depressive patients. A recently introduced melatonin analog, agomelatine, is also efficient for the treatment of major depressive disorder and bipolar affective disorder. Melatonin’s role as a ‘photoperiodic molecule’ in seasonal reproduction has been established in photoperiodic species, although its regulatory influence in humans remains under investigation. Taken together, this evidence implicates melatonin in a broad range of effects with a significant regulatory influence over many of the body’s physiological functions.

Introduction

Article

Jul 2005

Russel J Reiter

McGraw-Hill Yearbook of Science and Technology

Article

Oct 1964
SOIL SCI

I. DAVID

Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GARotating night shifts and risk of breast cancer in women participating in the Nurses' Health Study. J Natl Cancer Inst 93: 1563-1568

Article

Feb 2002
EUR J CANCER

Eva S Schernhammer

Electric power, melatonin, and breast cancer

Conference Paper

Aug 1987

R.G. Stevens

In this paper, the epidemiology of breast cancer will be discussed, followed by a brief description of the effect of electric fields on melatonin and the relation of melatonin to mammary cancer in rats. Finally, there will be a consideration of factors such as alcohol that affect melatonin and their relation to breast cancer risk. 55 refs.

Breast Cancer Among Women Who Work at Night

Article

Sep 2001
EPIDEMIOLOGY

Johnni Hansen

Environmental influences in cancer aetiology

Article

Jul 2009

Purpose. The purpose of this review is to inform both scientists and clinicians about the increase in cancer incidence throughout the Western World and to discuss environmental influences in cancer aetiology, in order to stimulate thoughts about plausible aetiological mechanisms and possible preventative measures. Design. Literature review. Materials and methods. This review was conducted by searching biomedical databases such as PubMed and Medline. Further research to obtain cancer incidence data involved accessing UK cancer registries, major cancer charities and government statistical records from the Office of National Statistics, the Department of Health, and the Department of Environment, Food and Rural Affairs. Results. Cancer incidence rates have increased in the Western World and this increased incidence affects the whole age spectrum. Epidemiological studies have provided some evidence of an association between exposure to environmental contaminants such as organochlorines and increased cancer risk. However, many epidemiological studies have been inconclusive. Similar reviews concerning environmental influences in cancer aetiology concluded that exposures to carcinogenic or endocrine‐disrupting chemicals exist at concentrations too low or have carcinogenic potential too weak to be considered a major factor in cancer aetiology. However, animal and in vitro studies together with epidemiological evidence discussed in this review would dispute that claim; even if healthy adults are not at risk, it would seem that the developing foetus, infant, child and young adults are at risk. In addition, studies discussed in this review show that low oestrogenic potency cannot be used as a marker of the capability of a chemical to cause oestrogenic responses and endocrine disruption. Genetic polymorphisms, which can predispose people to cancer, may interact with environmental contaminants such as organochlorines and endocrine disrupters, thus providing a modifying effect. Prevention measures have hitherto predominately centred on tobacco smoking cessation and diet education. Anecdotal evidence from practising physicians in pre‐industrial and traditional living societies, i.e. Canadian Inuits and Brazilian Indians suggests malignant disease was rare. A relatively new theory other than the somatic mutation theory has been proposed, the main premise being that carcinogenesis is a problem of tissue organization, comparable with organogenesis. Conclusions. It is feasible that chemical environmental contaminants, in particular synthetic pesticides and organochlorines with endocrine‐disrupting properties, could be major factors in cancer aetiology, particularly for hormone‐dependent malignancies, such as breast, testicular and prostate cancers. Animal and in vitro studies provide good evidence of a feasible mechanism whereby environmentally relevant levels of organochlorines and substances of low oestrogenic potency can cause endocrine disruption and consequently malignant disease. In addition, low oestrogenic potency should not be used as a marker of the capability of a chemical to cause oestrogenic responses and endocrine disruption. Preventative measures other than education about tobacco, diet and the promotion of physical activity should be considered. Moreover, it seems to be the most vulnerable members of society: the developing foetus, the developing child and adolescent and the genetically predisposed, who are at risk of developing cancer following involuntary exposure to environmental contaminants. This may be an appropriate time for governments to adopt the precautionary principle until substances to which members of society are involuntarily exposed are proved safe from long‐term, low‐level effects on human health. The World Health Organization estimates that between 1 and 5% of malignant disease in developed countries is attributable to environmental factors: it is possible that this figure may be underestimated. Anecdotal evidence suggests that cancer may be a disease of industrialization. Further research into the tissue organization field theory may be warranted, as some forms of pre‐malignant states are attributed to dysorganogenesis, for example an undescended testis.

Variation of electroencephalographic activity during NREM and REM sleep with phase of circadian melatonin rhythm in humans

Article

Sep 2004
J PHYSIOL-LONDON

The circadian pacemaker regulates the timing, structure and consolidation of human sleep. The extent to which this pacemaker affects electroencephalographic (EEG) activity during sleep remains unclear. To investigate this, a total of 1.22 million power spectra were computed from EEGs recorded in seven men (total, 146 sleep episodes; 9 h 20 min each) who participated in a one‐month‐long protocol in which the sleep–wake cycle was desynchronized from the rhythm of plasma melatonin, which is driven by the circadian pacemaker. In rapid eye movement (REM) sleep a small circadian variation in EEG activity was observed. The nadir of the circadian rhythm of α‐activity (8.25–10.5 Hz) coincided with the end of the interval during which plasma melatonin values were high, i.e. close to the crest of the REM sleep rhythm. In non‐REM sleep, variation in EEG activity between 0.25 and 11.5Hz was primarily dependent on prior sleep time and only slightly affected by circadian phase, such that the lowest values coincided with the phase of melatonin secretion. In the frequency range of sleep spindles, high‐amplitude circadian rhythms with opposite phase positions relative to the melatonin rhythm were observed. Low‐frequency sleep spindle activity (12.25–13.0 Hz) reached its crest and high‐frequency sleep spindle activity (14.25–15.5Hz) reached its nadir when sleep coincided with the phase of melatonin secretion. These data indicate that the circadian pacemaker induces changes in EEG activity during REM and non‐REM sleep. The changes in non‐REM sleep EEG spectra are dissimilar from the spectral changes induced by sleep deprivation and exhibit a close temporal association with the melatonin rhythm and the endogenous circadian phase of sleep consolidation.

Light in the Built Environment: Potential role of Circadian Disruption in Endocrine Disruption and Breast Cancer

Article

Jan 2001

Life in industrialized societies is primarily life inside buildings. Illumination from electric lighting in the built environment is quite different from solar radiation in intensity, spectral content, and timing during the 24-hour daily period. Humans evolved over millions of years with the day–night pattern of solar radiation as the primary circadian cue. This pattern maintained a 24-hour rhythm of melatonin release, as well as a host of other physiological rhythms including the sleep–wake cycle. Electric lighting in the built environment is generally more than sufficient for visual performance, but may be inappropriate for the maintenance of normal neuroendocrine rhythms in humans; e.g., insufficient during the day and too much at night. Lighting standards and engineering stress visual performance, whereas circadian function is not currently emphasized. The molecular biological research on the circadian clock and on mechanisms of phototransduction makes it clear that light for vision and light for circadian function are not identical systems. In particular, if electric lighting as currently employed contributes to `circadian disruption' it may be an important cause of `endocrine disruption' and thereby contribute to a high risk of breast cancer in industrialized societies.

The impact of shift and night work on health

Article

Mar 1996
APPL ERGON

Giovanni Costa

Shift work, in particular night work, can have a negative impact on health and well-being of workers as it can cause: (a) disturbances of the normal circadian rhythms of the psychophysiological functions, beginning with the sleep/wake cycle; (b) interferences with work performance and efficiency over the 24 hour span, with consequent errors and accidents; (c) difficulties in maintaining the usual relationships both at family and social level, with consequent negative influences on marital relations, care of children and social contacts; (d) deterioration of health that can be manifested in disturbances of sleeping and eating habits and, in the long run, in more severe disorders that deal prevalently with the gastrointestinal (colitis, gastroduodenitis and peptic ulcer), neuro-psychic (chronic fatigue, anxiety, depression) and, probably, cardiovascular (hypertension, ischemic heart diseases) functions. Besides, shift and night work may have more specific adverse effects on women's health both in relation to their particular hormonal and reproductive function, and their family roles. It has been estimated that about 20% of all workers have to leave shift work in a very short time because of serious disturbances; those remaining in shift work show different levels of (mal)adaptation and (in)tolerance, that can become more or less manifest in different times, and with different intensity. In fact, the effects of such stress condition can vary widely among the shift workers in relation to many ‘intervening variables’ concerning both individual factors (e.g. age, personality traits, physiological characteristics), as well as working situations (e.g. work loads, shift schedules) and social conditions (e.g. number and age of children, housing, commuting).

In Short Photoperiods, Human Sleep Is Biphasic

Article

Jun 1992
J SLEEP RES

Thomas A. Wehr

Results of a photoperiod experiment show that human sleep can be unconsolidated and polyphasic, like the sleep of other animals. When normal individuals were transferred from a conventional 16-h photoperiod to an experimental 10-h photo-period, their sleep episodes expanded and usually divided into two symmetrical bouts, several hours in duration, with a 1-3 h waking interval between them. The durations of nocturnal melatonin secretion and of the nocturnal phase of rising sleepiness (measured in a constant routine protocol) also expanded, indicating that the timing of internal processes that control sleep and melatonin, such as circadian rhythms, had been modified by the change in photoperiod. Previous work suggests that the experimental results could be simulated with dual-oscillators, entrained separately to dawn and dusk, or with a two-process model, having a lowered threshold for sleep-onset during the scotoperiod.

Carcinogenicity of Shift-work, Painting, and Fire-fighting

Article

Jan 2008

Akerstedt, T., Fröberg, J. E., Friberg, Y. & Wetterberg, L. Melatonin excretion, body temperature and subjective arousal during 64 hours of sleep deprivation. Psychoneuroendocrinology 4, 219-225

Article

Aug 1979
PSYCHONEUROENDOCRINO

(1) Evidence has been presented, based on measurement of melatonin by radioimmunoassay in 12 healthy males, that the urinary excretion of melatonin follows a circadian pattern in humans during sleep deprivation when the subjects are exposed to light. (2) Melatonin excretion increased with increased sleep deprivation. (3) Melatonin excretion during recovery sleep did not differ from that during base line sleep. (4) Melatonin excretion did not react to psychosocial stress at trough times (as adrenaline did). (5) Self-rated fatigue and body temperature exhibited a circadian variation. (6) Peak fatigue and trough body temperature coincided temporally with the peak of melatonin excretion.

Interleukin-6 and renal cell cancer: Production, regulation, and growth effects

Article

Feb 1992

Interleukin-6 (IL-6) is a recently characterized pleiotropic cytokine with antitumor activity. We investigated the production of IL-6 by renal cell cancer (RCC) and the growth effects of IL-6 on RCC. Using immunoperoxidase staining, cytoplasmic IL-6 was detected in four of four renal tumor lines and in tumor cells from freshly nephrectomized RCC. We found that IL-6 mRNA was expressed at basal culture conditions by seven of ten RCC tumor lines tested. Biologically active IL-6, as measured by the B9 assay, was produced by all ten RCC tumor lines. The addition of tumor necrosis factor alpha (TNF alpha) significantly augmented the expression of IL-6 mRNA in five RCC tumor lines (P less than 0.05). The combination of interferon gamma IFN gamma and TNF alpha further enhanced the augmented IL-6 mRNA accumulation seen with TNF alpha alone (P less than 0.05). TNF alpha also significantly stimulated the production of biologically active IL-6 (P less than 0.01). Furthermore, IFN gamma and TNF alpha were found to enhance IL-6 bioactivity synergistically (P less than 0.05). The growth effects of IL-6 on RCC were also investigated in two experimental systems: IL-6 was found to stimulate proliferative responses in six of six RCC tumor lines as measured by thymidine-uptake assays; however, only one of six tumor lines displayed an increase in proliferative response of greater than 21% (113%). The growth effect of IL-6 was further tested in clonogenic assays. One of the tumor lines tested displayed an enhanced growth response of up to 200%. We conclude that IL-6 is produced by RCC; this production is enhanced by TNF alpha with synergistic effects seen with IFN gamma at both mRNA and protein levels. In turn, IL-6 may have a modest stimulatory growth effect on certain RCC tumor lines.

Melatonin: The chemical expression of darkness

Article

Sep 1991
MOL CELL ENDOCRINOL

Russel J Reiter

Ultrashort sleep-waking schedule. III. 'Gates' and 'Forbidden zones' for sleep

Article

Jun 1986
Electroencephalogr Clin Neurophysiol

Peretz Lavie

Three experiments which utilized an ultrashort sleep-waking cycle were conducted to investigate the 24 h structure of sleepiness after 1 night of sleep deprivation under 2 experimental conditions: instructing subjects to attempt to fall asleep or instructing subjects to attempt to resist sleep. Six subjects participated in experiment 1. At 19.00 h they started a 13 min waking-7 min sleep attempt, or 13 min waking-7 min resisting sleep, until 19.00 h on the next day. Eight subjects were tested in a similar way in experiment 2, which started at 07.00 h after a night of sleep deprivation and lasted for 24 h. Eight subjects were similarly tested in experiment 3 which started at 11.00 h after a night of sleep deprivation and lasted for 36 h until 23.00 h on the next day. The results showed that in spite of the significant between-group differences in total sleep, the temporal structure of sleepiness was very similar in the 3 experiments. In each there was a bimodal distribution of sleepiness: a major nocturnal sleepiness crest and a secondary mid-afternoon sleepiness peak. These were separated by a 'forbidden zone' for sleep centred at around 20.00-22.00 h. The onset of the nocturnal sleep period (the sleep gate) was found to be a discrete event occurring as an 'all or none' phenomenon. Its timing was stable over a 2 week period, and independent of the specific experimental demands; there were no significant differences between the AS and RS conditions with respect to total sleep time or any of the sleep stages. These results, which demonstrate structured variations in sleepiness across the nycthemeron are discussed in the light of the recent modelling of sleep along homeostatic principles.

Electric power use and breast cancer: A hypothesis

Article

May 1987
AM J EPIDEMIOL

RICHARD G. STEVENS

It is the purpose of this paper to present the hypothesis that use of electric power may increase risk of breast cancer. The hypothesis is based on experimental evidence that shows an effect of light and extremely low frequency electric and/or magnetic (ELF) fields on pineal melatonin production, and on the relationship of melatonin to mammary carcinogenesis. A brief discussion of the epidemiology of breast cancer will be followed by a description of the experimental foundation for the hypothesis. 20 references, 1 figure.

Decreased nocturnal plasma melatonin peak in patients with estrogen positive breast cancer

Article

Jun 1982

Plasma melatonin concentrations were determined over a period of 24 hours in 20 women with clinical stage I or II breast cancer. In ten of the patients, whose tumors were estrogen receptor positive, the nocturnal increase in plasma melatonin was much lower than that observed in eight control subjects. Women with the lowest peak concentration of melatonin had tumors with the highest concentrations of estrogen receptors. A significant correlation was found between the peak plasma melatonin concentration and the tumor estrogen receptor concentration in 19 of the patients. These data suggest that low nocturnal melatonin concentrations may indicate the presence of estrogen receptor positive breast cancer and could conceivably have etiologic significance.

Extended sleep in humans in 14 hour nights (LD 10:14): relationship between REM density and spontaneous awakening

Article

Apr 1994
Electroencephalogr Clin Neurophysiol

The sleep patterns of 8 normal subjects living in a winter-type photoperiod (10 h light and 14 h darkness; LD 10:14) for 4 weeks were characterized by the presence of periods of spontaneous wakefulness alternating with periods of spontaneous sleep. Transitions from sleep to wakefulness occurred much more frequently out of REM sleep than out of NREM sleep (P < 0.002). REM periods that terminated in wakefulness showed shorter REM durations (P < 0.0005) and higher REM densities (P < 0.0005) than REM periods that did not terminate in wakefulness. The authors discuss these results in terms of a possible relationship between REM density and arousal level. The higher REM density preceding wakefulness and the increased number of REM periods terminating in spontaneous awakenings could reflect an enhanced level of a brain arousing process, resulting from reduced sleep pressure in the extended nights.

Temporal Organization: Reflections of a Darwinian Clock-Watcher

Article

Feb 1993

C S Pittendrigh

Melatonin in human breast cancer tissue: Association with nuclear grade and estrogen receptor status

Article

Nov 1996

The pineal hormone melatonin has been reported to inhibit tumor growth in a variety of experimental and clinical situations and to be an important immunoregulatory agent. Cancer patients with mammary or prostate tumors show reduced levels of circulating melatonin. Melatonin might, thus, be involved in the development of the malignant disease and act directly on tumor cells. Melatonin concentration in human neoplastic and adipose tissue sampled from mastectomy or tumorectomy products (n = 15) was measured by high-performance liquid chromatography. Melatonin seemed to be 3 orders of magnitude more concentrated in the neoplastic and adipose tissues of the breast than in sera from healthy subjects or cancer patients. Few samples (n = 3) of normal breast tissues showed equally elevated concentrations of melatonin. Most interestingly, we found a significant inverse correlation between nuclear grade and melatonin concentration (p < 0.006) and a positive association between melatonin and estrogen receptor status (p < 0.02). No correlation between age of the patients and melatonin concentration was evident. Melatonin might be produced in situ by mammary epithelial cells and represent a good prognostic marker. The possibility that exogenous melatonin might influence nuclear grade and/or estrogen receptor activity in breast cancer patients should be investigated.

Variation of electroencephalographic activity during non-rapid eye movement and rapid eye movement sleep with phase of circadian melatonin rhythm in humans

Article

Jan 1998

1. The circadian pacemaker regulates the timing, structure and consolidation of human sleep. The extent to which this pacemaker affects electroencephalographic (EEG) activity during sleep remains unclear. 2. To investigate this, a total of 1.22 million power spectra were computed from EEGs recorded in seven men (total, 146 sleep episodes; 9 h 20 min each) who participated in a one-month-long protocol in which the sleep-wake cycle was desynchronized from the rhythm of plasma melatonin, which is driven by the circadian pacemaker. 3. In rapid eye movement (REM) sleep a small circadian variation in EEG activity was observed. The nadir of the circadian rhythm of alpha activity (8.25-10.5 Hz) coincided with the end of the interval during which plasma melatonin values were high, i.e. close to the crest of the REM sleep rhythm. 4. In non-REM sleep, variation in EEG activity between 0.25 and 11.5 Hz was primarily dependent on prior sleep time and only slightly affected by circadian phase, such that the lowest values coincided with the phase of melatonin secretion. 5. In the frequency range of sleep spindles, high-amplitude circadian rhythms with opposite phase positions relative to the melatonin rhythm were observed. Low-frequency sleep spindle activity (12.25-13.0 Hz) reached its crest and high-frequency sleep spindle activity (14.25-15.5 Hz) reached its nadir when sleep coincided with the phase of melatonin secretion. 6. These data indicate that the circadian pacemaker induces changes in EEG activity during REM and non-REM sleep. The changes in non-REM sleep EEG spectra are dissimilar from the spectral changes induced by sleep deprivation and exhibit a close temporal association with the melatonin rhythm and the endogenous circadian phase of sleep consolidation.

Increased Breast Cancer Risk among Women Who Work Predominantly at Night

Article

Feb 2001
EPIDEMIOLOGY

Johnni Hansen

Irregular working hours, including working at night, have serious psychological and physiological effects. In a nationwide population-based case-control study, we investigated the breast cancer risk among 30- to 54-year-old Danish women who worked predominantly at night. Individual employment histories were reconstructed back to 1964 for each of 7035 women with breast cancer and their individually matched controls from the records of a nationwide pension scheme with compulsory membership. Odds ratios, including 5 years of induction time and adjusted for socio-economic status, age at the birth of first and last child and number of children, were estimated by conditional logistic regression analysis. The odds ratio for breast cancer among women who worked at night at least half of a year was 1.5 (95% confidence interval, 1.2 to 1.7), and there was a tendency to increasing odds ratio by increasing duration of nighttime employment.

The Temporal Organization of Life: the Impact of Multi-frequency Non-linear Biologic Time Structure Upon the Host-Cancer Balance

Article

Jan 2001

W.J.M. Hrushesky

The current scientific paradigm, based upon an erroneous assumption of linear biologic reality and simple cause and effect relationships, has outlived its usefulness. In order to begin to turn the voluminous data the reductive process provides us with daily into meaningful understanding of life, it is essential to integrate these data within a complex, multi-frequency temporo-spatial framework. This rhythmic chronobiology more accurately depicts the life process, as well as its evolutionary and ongoing vital interaction with the pulsating cosmic resonance structure. Examples of the kinds of thinking and experiments necessary to exploit this new paradigm are provided.

Polyunsaturated fatty acids, melatonin, and cancer prevention

Article

Jul 2001
BIOCHEM PHARMACOL

Many nutritional, hormonal, and environmental factors affect carcinogenesis and growth of established tumors in rodents. In some cases, these factors may either enhance or attenuate the neoplastic process. Recent experiments performed in our laboratory using tissue-isolated rat hepatoma 7288CTC in vivo or during perfusion in situ have demonstrated new interactions among four of these factors. Two agents, dietary linoleic acid (C18:2n6) and "light at night," enhanced tumor growth, and two others, melatonin and n3 fatty acids, attenuated growth. Linoleic acid stimulated tumor growth because it is converted by hepatoma 7288CTC to the mitogen, 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin, the neurohormone synthesized and secreted at night by the pineal gland, and dietary n3 fatty acids are potent antitumor agents. Both inhibited tumor linoleic acid uptake and 13-HODE formation. Artificial light, specifically "light at night," increased tumor growth because it suppressed melatonin synthesis and enhanced 13-HODE formation. Melatonin and n3 fatty acids acted via similar or identical G(i) protein-coupled signal transduction pathways, except that melatonin receptors and putative n3 fatty acid receptors were used. The results link the four factors in a common mechanism and provide new insights into the roles of dietary n6 and n3 polyunsaturated fatty acid intake, "light at night," and melatonin in cancer prevention in humans.

Evidence for a biological dawn and dusk in the human circadian timing system

Article

Oct 2001

1. Because individuals differ in the phase angle at which their circadian rhythms are entrained to external time cues, averaging group data relative to clock time sometimes obscures abrupt changes that are characteristic of waveforms of the rhythms in individuals. Such changes may have important implications for the temporal organization of human circadian physiology. 2. To control for variance in phase angle of entrainment, we used dual internal reference points--onset and offset of the nocturnal period of melatonin secretion--to calculate average profiles of circadian rhythm data from five previously published studies. 3. Onset and/or offset of melatonin secretion were found to coincide with switch-like transitions between distinct diurnal and nocturnal periods of circadian rhythms in core body temperature, sleepiness, power in the theta band of the wake EEG, sleep propensity and rapid eye movement (REM) sleep propensity. 4. Transitions between diurnal and nocturnal periods of sleep-wake and cortisol circadian rhythms were found to lag the other transitions by 1-3 h. 5. When the duration of the daily light period was manipulated experimentally, melatonin-onset-related transitions in circadian rhythms appeared to be entrained to the light-to-dark transition, while melatonin-offset-related transitions appeared to be entrained to the dark-to-light transition. 6. These results suggest a model of the human circadian timing system in which two states, one diurnal and one nocturnal, alternate with one another, and in which transitions between the states are switch-like and are separately entrained to dawn and dusk. 7. This description of the human circadian system is similar to the Pittendrigh-Daan model of the rodent circadian system, and it suggests that core features of the system in other mammals are conserved in humans.

Health in a 24-h society

Article

Oct 2001

With increasing economic and social demands, we are rapidly evolving into a 24-h society. In any urban economy, about 20% of the population are required to work outside the regular 0800-1700 h working day and this figure is likely to increase. Although the increase in shiftwork has led to greater flexibility in work schedules, the ability to provide goods and services throughout the day and night, and possibly greater employment opportunities, the negative effects of shiftwork and chronic sleep loss on health and productivity are now being appreciated. For example, sleepiness surpasses alcohol and drugs as the greatest identifiable and preventable cause of accidents in all modes of transport. Industrial accidents associated with night work are common, perhaps the most famous being Chernobyl, Three Mile Island, and Bhopal.

Night Shift Work, Light at Night, and Risk of Breast Cancer

Article

Nov 2001

Exposure to light at night may increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin by the pineal gland, which, in turn, could increase the release of estrogen by the ovaries. This study investigated whether such exposure is associated with an increased risk of breast cancer in women. Case patients (n = 813), aged 20-74 years, were diagnosed from November 1992 through March 1995; control subjects (n = 793) were identified by random-digit dialing and were frequency matched according to 5-year age groups. An in-person interview was used to gather information on sleep habits and bedroom lighting environment in the 10 years before diagnosis and lifetime occupational history. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression, with adjustment for other potential risk factors. Breast cancer risk was increased among subjects who frequently did not sleep during the period of the night when melatonin levels are typically at their highest (OR = 1.14 for each night per week; 95% CI = 1.01 to 1.28). Risk did not increase with interrupted sleep accompanied by turning on a light. There was an indication of increased risk among subjects with the brightest bedrooms. Graveyard shiftwork was associated with increased breast cancer risk (OR = 1.6; 95% CI = 1.0 to 2.5), with a trend of increased risk with increasing years and with more hours per week of graveyard shiftwork (P =.02, Wald chi-squared test). The results of this study provide evidence that indicators of exposure to light at night may be associated with the risk of developing breast cancer.

Involvement of the MT1 melatonin receptor in human breast cancer

Article

Jun 2002
CANCER LETT

Two putative melatonin receptors have been described including the cell surface G-protein-linked receptors, mt1 and MT2, and the nuclear retinoic orphan receptor alpha (RORalpha). The mt1 receptor, but not the MT2 receptor, is expressed in human breast tumor cell lines, and melatonin-induced growth suppression can be mimicked by the mt1 and MT2 agonist, AMMTC, and blocked by the antagonist, CBPT. RORalpha receptors are also expressed in MCF-7 breast cancer cells and the putative RORalpha agonist CPG-52608 inhibits MCF-7 cell growth but with a very different dose-response than melatonin. Finally, melatonin and AMMTC, but not CPG-52608, can repress RORalpha transcriptional activity in MCF-7 cells.

A Longer Biological Night in Long Sleepers Than in Short Sleepers

Article

Jan 2003

Habitual sleep duration varies greatly among individuals. The physiological basis of this variation is unknown. We sought to determine whether individual differences in sleep duration are associated with systematic differences in the duration of the biological night that is programmed by the circadian pacemaker and reflected in the nocturnal interval of circadian rhythms in neuroendocrine function, body temperature, and arousal. Ten young, healthy long sleepers (sleep duration >9 h) and 14 short sleepers (<6 h) were studied under constant environmental conditions and in the absence of sleep. The nocturnal intervals of high plasma melatonin levels, increasing cortisol levels, low body temperature, and increasing sleepiness were longer in long sleepers than in short sleepers. The maxima in cortisol and sleepiness exhibited a close relationship to habitual wake-up time, which occurred approximately 2.5 h later in long sleepers than in short sleepers. It is concluded that the circadian pacemaker programs a longer biological night in long sleepers than in short sleepers. We propose that individual differences in the circadian pacemaker's program may contribute to the variability of sleep duration in the general population. The persistence or inertia of an individual's circadian program, as was evident in constant conditions, may underlie the commonly experienced difficulty of changing habitual sleep duration willfully.

Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans

Article

Aug 2004

Recent human studies suggested a supportive influence of regular nocturnal sleep on immune responses to experimental infection (vaccination). We hypothesized here that sleep could ease such responses by shifting the balance between T helper 1 (Th1) and T helper 2 (Th2) cytokine activity towards Th1 dominance thereby favoring cellular over humoral responses to infection. We compared the Th1/Th2 cytokine balance in 14 healthy men during regular nocturnal sleep (between 23:00 and 07:00 h) and while remaining awake during the same nocturnal interval, in a within-subject cross-over design. Blood was collected every 2 h. Production of T cell derived cytokines--interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha)--was measured at the single cell level using multiparametric flow cytometry. Also, several immunoactive hormones--prolactin, growth hormone (GH), thyroid stimulating hormone (TSH), cortisol, and melatonin--were measured, the release of which is known to be regulated by sleep. Compared with wakefulness, early nocturnal sleep induced a shift in the Th1/Th2 cytokine balance towards increased Th1 activity, as indicated by an increased (p <.05) ratio of IFN-gamma/IL-4 producing T helper cells. However, the Th1 shift was only of moderate size and replaced by Th2 dominance during late sleep (p <.05). It could be mediated via release of prolactin and GH which both were distinctly increased during sleep (p <.001). Though unexpected, the most pronounced effect of sleep on T cell cytokine production was a robust decrease in TNF-alpha producing CD8+ cells probably reflecting increased extravasation of cytotoxic effector and memory T cells.

Mechanisms of cancer inhibition by melatonin

Article

Nov 2004

Russel J Reiter

Urinary Melatonin Levels and Breast Cancer Risk

Article

Aug 2005
J NATL CANCER I

Exposure to light at night suppresses melatonin production, and night-shift work (a surrogate for such exposure) has been associated with an increased risk of breast cancer. However, the association between circulating melatonin levels and breast cancer risk is unclear. In a prospective case–control study nested within the Nurses' Health Study II cohort, we measured the concentration of the major melatonin metabolite, 6-sulphatoxymelatonin (aMT6s), in the first morning urine of 147 women with invasive breast cancer and 291 matched control subjects. In logistic regression models, the relative risk (reported as the odds ratio [OR]) of invasive breast cancer for women in the highest quartile of urinary aMT6s compared with those in the lowest was 0.59 (95% confidence interval [CI] = 0.36 to 0.97). This association was essentially unchanged after adjustment for breast cancer risk factors or plasma sex hormone levels but was slightly weakened when the analysis included 43 case patients with in situ breast cancer and their 85 matched control subjects (OR = 0.70, 95% CI = 0.47 to 1.06). The exclusion of women who had a history of night-shift work left our findings largely unchanged. These prospective data support the hypothesis that higher melatonin levels, as measured in first morning urine, are associated with a lower risk of breast cancer.

Melatonin, sleep disturbance and cancer risk

Abstract

No full-text available

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