ArticleLiterature Review

Melatonin, sleep disturbance and cancer risk

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Abstract

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.

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... Melatonin is also often called a hormone of darkness since all of the body's melatonin is secreted at night-time (63). Melatonin has been shown to have various anti-tumor effects, both in malignant brain tumors (64,65) and in other cancers (63,66). ...
... Melatonin is also often called a hormone of darkness since all of the body's melatonin is secreted at night-time (63). Melatonin has been shown to have various anti-tumor effects, both in malignant brain tumors (64,65) and in other cancers (63,66). Besides this protective role in malignant brain tumor patients, melatonin also has many other possible anti-tumor mechanisms, which link it to points mentioned earlier. ...
... The modern, industrialized lifestyle with its dependency on light disrupts significantly the synthesis and the secretion of melatonin (63,69). Even different diets have been found to affect the melatonin levels in the organism (70). ...
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Malignant brain tumors are among the most aggressive human neoplasms. One of the most common and severe symptoms that patients with these malignancies experience is sleep disruption. Disrupted sleep is known to have significant systemic pro-tumor effects, both in patients with other types of cancer and those with malignant brain lesions. We therefore provide a review of the current knowledge on disrupted sleep in malignant diseases, with an emphasis on malignant brain tumors. More specifically, we review the known ways in which disrupted sleep enables further malignant progression. In the second part of the article, we also provide a theoretical framework of the reverse process. Namely, we argue that due to the several possible pathophysiological mechanisms, patients with malignant brain tumors are especially susceptible to their sleep being disrupted and compromised. Thus, we further argue that addressing the issue of disrupted sleep in patients with malignant brain tumors can, not just improve their quality of life, but also have at least some potential of actively suppressing the devastating disease, especially when other treatment modalities have been exhausted. Future research is therefore desperately needed.
... Hvilket yrke man har kan også ha noe å si for søvn og helse. Dersom man jobber på natten, vil døgnrytmen forstyrres [35]. Ved eksponering for lys på nattestid vil utskillelse av søvnhormonet melatonin forsinkes. ...
... Ved eksponering for lys på nattestid vil utskillelse av søvnhormonet melatonin forsinkes. Melatonin er antatt å virke beskyttende på kreftutvikling, og det er funnet at nattarbeid kan ha sammenheng med flere krefttyper, deriblant brystkreft, prostatakreft, tarmkreft og livmorkreft [35]. Det er foreløpig uklart om kreftutvikling også har sammenheng med søvnforstyrrelser hvor døgnrytmen ikke blir forstyrret som ved skiftarbeid [35]. ...
... Melatonin er antatt å virke beskyttende på kreftutvikling, og det er funnet at nattarbeid kan ha sammenheng med flere krefttyper, deriblant brystkreft, prostatakreft, tarmkreft og livmorkreft [35]. Det er foreløpig uklart om kreftutvikling også har sammenheng med søvnforstyrrelser hvor døgnrytmen ikke blir forstyrret som ved skiftarbeid [35]. Etter at risikoen for utvikling av kreft ved å arbeide på natten ble kjent, har Verdens helseorganisasjon konkludert med at skiftarbeid som involverer døgnrytmeforstyrrelse via eksponering for lys på nattestid sannsynlig er kreftfremkallende for mennesker [36]. ...
Article
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Søvn gjennom livsløpet: konsekvenser for helsen Søvn utgjør en stor del av livet. Til sammen tilbringer vi omtrent en tredjedel av livet sovende. Både hvordan vi sover og hvor mye vi sover endrer seg gjennom hele livet, helt fra spedbarnsalder til alderdom. Det er viktig å tilrettelegge for god søvn i alle livets stadier for å opprettholde god helse gjennom hele livet.
... Disruption of circadian rhythms can occur due to changes in normal daily activities such as shift work, jet lag, unusual photoperiods (e.g., polar regions), or possibly due to sleep disorders (Blask, 2009;Mattis and Sehgal, 2016). Additionally, aging plays a critical role in causing sleep-related disorders among the elderly population. ...
... Evidence from the literature suggests that aged individuals demonstrate fragmented sleep patterns compared to younger individuals and that the duration of slow-wave sleep (SWS: deep sleep) decreases with increasing age (Mattis and Sehgal, 2016). Age-related neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's show signs of circadian disruption, which is indicative of older individuals having an increased susceptibility to circadian dysfunctionassociated clinical ailments including cancer risk (Blask, 2009;Abbott and Videnovic, 2016;Mattis and Sehgal, 2016). Generally, sleep helps maintain normal physiological processes such as brain development, plasticity, memory, learning and immunity (Bollinger et al., 2010;Abel et al., 2013; Figure 1). ...
... Melatonin is the hormone produced in the pineal gland during the dark (night), and its synthesis is directly controlled by the central clock (SCN) (Blask, 2009). Melatonin exerts its effects by binding to one of two melatonergic receptors, namely MT1 and MT2, both of which belong to the G protein-coupled receptor family. ...
Article
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected nearly 28 million people in the United States and has caused more than five hundred thousand deaths as of February 21, 2021. As the novel coronavirus continues to take its toll in the United States and all across the globe, particularly among the elderly (>65 years), clinicians and translational researchers are taking a closer look at the nexus of sleep, circadian rhythms and immunity that may contribute toward a more severe coronavirus disease-19 (COVID-19). SARS-CoV-2-induced multi-organ failure affects both central and peripheral organs, causing increased mortality in the elderly. However, whether differences in sleep, circadian rhythms, and immunity between older and younger individuals contribute to the age-related differences in systemic dysregulation of target organs observed in SARS-CoV-2 infection remain largely unknown. Current literature demonstrates the emerging role of sleep, circadian rhythms, and immunity in the development of chronic pulmonary diseases and respiratory infections in human and mouse models. The exact mechanism underlying acute respiratory distress syndrome (ARDS) and other cardiopulmonary complications in elderly patients in combination with associated comorbidities remain unclear. Nevertheless, understanding the critical role of sleep, circadian clock dysfunction in target organs, and immune status of patients with SARS-CoV-2 may provide novel insights into possible therapies. Chronotherapy is an emerging concept that is gaining attention in sleep medicine. Accumulating evidence suggests that nearly half of all physiological functions follow a strict daily rhythm. However, healthcare professionals rarely take implementing timed-administration of drugs into consideration. In this review, we summarize recent findings directly relating to the contributing roles of sleep, circadian rhythms and immune response in modulating infectious disease processes, and integrate chronotherapy in the discussion of the potential drugs that can be repurposed to improve the treatment and management of COVID-19.
... The peak concentration is approximatelty 10 pg/mL in blood and 3 pg/mL in the saliva (Benloucif et al, 2008). It is suggested that melatonin might be useful in the treatment of several diseases, such as depression (Cardinali et al, 2012), insomnia (Cardinali et al, 2012;Blask, 2009), obesity (Tan et al, 2011;Agil et al, 2012), diabetes (Agil et al, 2012), cancer (Blask, 2009), immune (Calvo et al, 2013) and cardiac disorders (Paulis and Simko, 2007). It can forage ROS by increasing antioxidant enzyme activities and its antioxidant properties (Singh and Jadhav, 2014). ...
... The peak concentration is approximatelty 10 pg/mL in blood and 3 pg/mL in the saliva (Benloucif et al, 2008). It is suggested that melatonin might be useful in the treatment of several diseases, such as depression (Cardinali et al, 2012), insomnia (Cardinali et al, 2012;Blask, 2009), obesity (Tan et al, 2011;Agil et al, 2012), diabetes (Agil et al, 2012), cancer (Blask, 2009), immune (Calvo et al, 2013) and cardiac disorders (Paulis and Simko, 2007). It can forage ROS by increasing antioxidant enzyme activities and its antioxidant properties (Singh and Jadhav, 2014). ...
Article
The present study was designed to evaluate the effect of melatonin and different photoperiods on lung biomarkers of pulmonary fibrosis in diabetic albino rat. Experiment was performed in two sets. In set-1, the rats were made diabetic and then treated with melatonin and in set-2 diabetic rats were treated with different photoperiods such as Long Photoperiod (LP; 20L:4D), Short Photoperiod (SP; 4L:20D) and natural day length for control group. Circulatory glucose level, insulin, MMP-1, MMP-2, MMP-7 and surfactant proteins as well as accumulation of collagen fibres in lung tissue increased in diabetic rats. Treatment with melatonin and short photoperiod decreased accumulation of collagen in lung tissue as well as circulatory glucose level, insulin, MMP-1, MMP-2, MMP-7 and surfactant proteins. Long photoperiod increased all the parameters. Such relationship between all the studied biomarkers shows that diabetes could be one of the factors responsible for idiopathic pulmonary fibrosis and melatonin and short photoperiod might be helpful in treatment of secondary complications of diabetes.
... Participants working under bright light conditions reported higher subjective alertness and improved mood (Smolders et al., 2012;Leichtfried et al., 2015), showed better sustained attention (Smolders et al., 2012), better response and conflict inhibition (Ru et al., 2019), better performance on tasks for working memory (Huiberst et al., 2016) and long-term memory (Zhu et al., 2017). More specifically, in shift work, appropriate lighting conditions are of additional relevance as disturbed hormonal regulations and physiological processes are typical consequences of shift work due to the mismatch between the light-dark pattern and the sleep-wake rhythm (Blask, 2009). Night work reduces the duration of darkness per day by several hours (Rabstein et al., 2019). ...
... We included two comparable groups of shift workers who worked on the same production line in a truck assembly factory but were exposed to the different light settings. We particularly chose to focus on shift workers (two-shift system), because the sleep-wake pattern is often disturbed in this population due to the early rising time in the morning, causing sleep problems during the night and fatigue and reduced alertness during the day (Blask et al., 2009). A objective assessment of sleep, objective measurements of cognition (alertness, concentration and inhibition) and a subjective measurement of visual comfort were administered before and after the changed light settings. ...
Article
It is well known that exposure to light at the right time of the day is important to synchronise our circadian rhythm and enhance cognitive functioning. There is, however, a lack of field studies investigating which lighting characteristics are necessary to improve sleep and cognitive functioning. A controlled field study with 80 shift workers was set up, in which the impact of an integrative lighting (IL) scenario was investigated during the morning shift. Two groups were compared: a control group (no change in lighting settings) and a IL-group (exposed to a melanopic Equivalent Daylight Illuminance of 192 lux, i.e., bright light with a high fraction of short-wavelengths). Pre-post measurement of visual comfort, cognitive functioning (D2 task, go-nogo reaction time task) and sleep (MotionWatch8) were performed. The IL-settings ameliorated sleep efficiency and sleep latency during morning shift and enhanced alertness (not inhibition) compared to standard lighting conditions. Changing lighting settings in an industrial setting should be considered as it seems worthwhile for employees’ sleep and cognitive performance.
... This may mean that sleep deficits can play a large role in chronic diseases affected by biological clock-associated proteins. There also may be an effect due to the pineal hormone melatonin, which is involved in circadian regulation and facilitation of sleep, inhibition of cancer growth, and enhancement of immune function [27,32]. However, there are also effects of sleep and the immune system that are independent of melatonin, indicating that sleep disruption could lead to immune suppression and lead to predominance in cancer-stimulatory cytokines [32]. ...
... There also may be an effect due to the pineal hormone melatonin, which is involved in circadian regulation and facilitation of sleep, inhibition of cancer growth, and enhancement of immune function [27,32]. However, there are also effects of sleep and the immune system that are independent of melatonin, indicating that sleep disruption could lead to immune suppression and lead to predominance in cancer-stimulatory cytokines [32]. A weakened immune system could ultimately impact CRC survivorship, negatively affecting the ability to fight a CRC diagnosis. ...
Article
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Purpose: Sleep quality in relation to anatomic site among colorectal cancer (CRC) patients is not well understood, though discerning the relationship could contribute to improved survivorship care. Methods: We ascertained sleep quality (Pittsburgh Sleep Quality Index) and other personal characteristics within an ongoing population-based study of CRC patients identified through a cancer registry (N = 1453). Differences in sleep quality by CRC site were analyzed using chi-square and ANOVA tests. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of tumor site with sleep quality concerns, adjusting for patient attributes and time since diagnosis. Results: Sleeping problems were reported by 70% of CRC patients. Overall, participants with rectal (vs. colon) cancer were more likely (OR (95% CI)) to report general trouble sleeping (1.58 (1.19, 2.10)). Rectal cancer patients were also more likely than colon cancer patients to report changes in sleep patterns after cancer diagnosis (1.38 (1.05, 1.80)), and trouble sleeping specifically due to getting up to use the bathroom (1.53 (1.20, 1.96)) or pain (1.58 (1.15, 2.17)), but were less likely to report trouble sleeping specifically due to issues with breathing/coughing/snoring (0.51 (0.27, 0.99)). Conclusion: Overall, rectal cancer patients were more likely to have sleep complications compared to colon cancer patients. This suggests sleep-focused survivorship care may be adapted according to CRC site to ensure patients receive appropriate support.
... Several studies found that administration of antipsychotic drugs such as haloperidol or fluvoxamine can induce CRSD such as DSWPD [ [ 14,15,16,17,18,19,20 ]. Modern living styles characterized by nocturnal living patterns, shift-time work, and working in offices with little variation in illumination throughout the day and night may also induce disorders in biological rhythm. ...
... Therefore, continuous exposure to nighttime illumination from digital media devices may be a risk factor to developing sleep or sleep/wake circadian disorders. It is well-established in the sleep literature that targeted exposure to bright ALAN can delay sleep onset and melatonin secretion [ 14,15,16,23,24 ], and therefore is considered an effective treatment for circadian rhythms sleep disorders [ 25,26 ]. In our opinion, extended exposure to light from digital screens at night is in practice a form of unintended "light therapy" that affects the circadian clock and its derivatives and consequently influences sleep capacity and quality. ...
Chapter
Circadian rhythm sleep disorders (CRSD) are a group of sleep disorders characterized by a de-synchronization between a person's biological clock and the environmental 24-h schedule. There are six main types of CRSD, namely, advanced sleep phase syndrome (ASPD), delayed sleep phase disorder (DSPD), irregular sleep-wake rhythm (ISWR), free running disorder (FRD), shift work type (SWD), and jet lag disorder (JLD). Physiological data and genetic studies in patients with CRSDs suggest that these disorders result from abnormal functioning of the circadian rhythm system. The diagnosis of CRSD is based on clinical interview and sleep log diaries and/or actigraphic monitoring under a free condition schedule. Bright-light therapy and melatonin administration have proved to be the most effective treatments for CRSD. Difficulties in daytime functioning are one of the prominent characteristics of CRSDs. Individuals with CRSDs frequently fail to adjust to the normal accepted hours of activity. It is common that the daytime functional difficulties that accompany CRSDs are misinterpreted as symptoms of psychopathology or daily dysfunction. CRSDs are under-recognized and frequently misdiagnosed, and therefore treated as psychological, psychiatric, and/or sleep disorders. Recognition and awareness of the characterization of these disorders should improve the diagnosis and treatment of these patients. Keywords Circadian rhythm sleep disorders Insomnia Hypersomnia Depression 14.1. Introduction Humans need to adjust their behavior and physiological processes to the conditions of a 24-h day-night (light-dark) period. Synchronization of the endogenous clock with environmental conditions enables the rhythmic changes of behavior and physiological processes to be in phase with the external world. The synchronizing factors are clear environmental cues (so-called time givers-"zeitgebers"), the most prominent of which to the central clock in the SCN is light. Alternating periods of light and dark, day and night, are cues that enforce the period of activity and sleep. Sleep is regulated by two main factors [ 1 ]: the model posits that a homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C), with time-courses derived from physiological and behavioral variables-the homeostatic pressure and the circadian timing-and the interaction between them. The homeostatic pressure to sleep accumulates as long as a person is awake and therefore the pressure to sleep increases in a positive correlation with the awake time. The circadian factor plays a role in the timing of the sleep; this means that there is a time of day that the probability to fall asleep is higher, for example, in the afternoon between 1 and 4 p.m. and at night between 0 and 4 a.m. The interaction between these two factors will determine the timing and length of sleep [ 1 ]. Circadian rhythm sleep disorders (CRSDs) are a group of sleep disorders characterized by an asynchronization between a person's biological clock and the environmental 24-h schedule. These disorders can lead to harmful psychological and functional difficulties and are often misdiagnosed and incorrectly treated due to the fact that physicians are unaware of their existence. In the current chapter we describe the characteristics of CRSDs, its diagnosis and treatment, as well as the relationship to daily dysfunction and disabilities. Affiliationids : Aff1 Aff2, Correspondingaffiliationid : Aff2 Affiliationids : Aff1 Aff2
... Evidence on the use of melatonin supplementation is currently inconclusive. Although some studies have shown nocturnal melatonin supplementation to be effective in inhibiting the growth of existing tumors, a bolus of exogenous melatonin in a tumor-free individual may result in a phase shift that contributes to circadian disruption rather than alleviates it (Blask, 2009;Stevens, 2006). Others have therefore suggested the potential value of circadian-timed melatonin supplementation as a preventive or therapeutic agent (Blask, 2009). ...
... Although some studies have shown nocturnal melatonin supplementation to be effective in inhibiting the growth of existing tumors, a bolus of exogenous melatonin in a tumor-free individual may result in a phase shift that contributes to circadian disruption rather than alleviates it (Blask, 2009;Stevens, 2006). Others have therefore suggested the potential value of circadian-timed melatonin supplementation as a preventive or therapeutic agent (Blask, 2009). ...
Article
Breast cancer is increasingly prevalent in industrialized regions of the world, and exposure to light at night (LAN) has been proposed as a potential risk factor. Epidemiological observations have documented an increased breast cancer risk among female night-shift workers, and strong experimental evidence for this relationship has also been found in rodent models. Indirect support for the LAN hypothesis comes from studies involving blind women, sleep duration, bedroom light levels, and community nighttime light levels. This article reviews the literature, discusses possible mechanisms of action, and provides recommendations for occupational health nursing research, practice, and education. Research is needed to further explore the relationship between exposure to LAN and breast cancer risk and elucidate the mechanisms underlying this relationship before interventions can be designed for prevention and mitigation of breast cancer.
... Artificial light at night is of major concern to the epidemiologist and oncologist based on its implication in cancer of breast in females and prostate cancer in males (Haim and Portnov, 2014; Al-Naggar and Anil, 2016; Garcia-Saenz et al., Haim et al., 2019). [1][2][3][4] The consequences and negative impact of exposure to light reported was directly linked to its ability to suppress melatonin (Falchi et al., 2011;Haim and Zubidat, 2015), [5,6] an ubiquitous hormone known to play vital roles in the survival of animals due to its activity in combating oxygen radicals (Blask, 2009;Reiter et al., 2011 andGuerrero et al., 2013). [7][8][9] Melatonin is responsible for various physiological processes (Barrenetxe et al., 2004;Golan et al., 2018) [10][11] in the body and any alteration in its activity could be detrimental to the body. ...
... [1][2][3][4] The consequences and negative impact of exposure to light reported was directly linked to its ability to suppress melatonin (Falchi et al., 2011;Haim and Zubidat, 2015), [5,6] an ubiquitous hormone known to play vital roles in the survival of animals due to its activity in combating oxygen radicals (Blask, 2009;Reiter et al., 2011 andGuerrero et al., 2013). [7][8][9] Melatonin is responsible for various physiological processes (Barrenetxe et al., 2004;Golan et al., 2018) [10][11] in the body and any alteration in its activity could be detrimental to the body. Moreover, previous studies focus mostly on the effect of white light on the activity of melatonin (Haim and Portnov, 2014) [1] but recent studies have shown that all the light spectra have the potential to suppress melatonin, this time with respect to the light intensity (Zubidat et al., 2011;Haim et al., 2019). ...
Article
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Artificial light at night is considered as environmental stressor depending largely on the spectra. Haematological parameters have been used as bio-indicator of stress when animals are subjected to unfavourable environmental condition. Hence this study evaluated the effect of various spectra of light on the haematology of albino rats. Day old rats were exposed to blue (BL), green (GL), yellow (YL), red (RL) and white (WL) lights at night while darkness (DD) and ambient light (CL) served as control. Compact florescent bulbs were used and light intensity maintained at 300 lux. At days 35, 63, 91 and 126, six rats per treatment and per sex were euthanized. Blood was collected and analysed for haematocrit (Hct), haemoglobin (Hb) and red blood cells (RBC). At d35 and d63, Hct and Hb and RBC were significantly (p < 0.05) low in male and female rats exposed to coloured light. Hct and Hb recorded in the male rats exposed to green light and female rats exposed to blue and green lights were lower than the normal physiological range for rats at these ages bracket. Further exposure to light at d91 and d126 showed no negative effects on blood parameters. Linear regression showed significant increase in the blood parameter with time on exposure to coloured light which together signifies adaptation. Exposure to light of high energy (BL and GL) and WL during prepubertal could be detrimental. Normal day and night light cycle provided the optimum environmental lighting condition for adequate homeostatic of the blood in rats.
... Plusieurs mécanismes potentiels ont été identifiés, y compris l'augmentation de la pression artérielle, l'hyperactivité sympathique ou l'intolérance au glucose (Grandner et al., 2012(Grandner et al., , 2016Newman et al., 1997). Par ailleurs, un lien entre les troubles du sommeil et le risque d'apparition de certains cancers (colon, sein, endomètre…) a été évoqué dans la littérature (Blask, 2009). Par exemple, des études longitudinales ont rapporté une diminution du risque de cancer du sein allant de 38 à 72% chez les femmes ayant une durée de sommeil adéquate (Pinheiro et al., 2006;Verkasalo et al., 2005;Zhao et al., 2013). ...
Thesis
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Physical activity and ingested nutrients take part in the regulation of the internal clock and sleep physiology. Recently, there has been a surge of interest in this topic. However, studies remain almost exclusively limited to adults. Adolescence is marked by critical transitions that may trigger several behavioral disturbances particularly with regard to sleep. A problem compounded by an array of endogenous and exogenous factors forming the so called “Perfect Storm” of both altered sleep duration and quality. Obesity and elite sport are two factors that have been separately associated with sleep disturbances, and have a negative impact on holistic development, with lowered performance and altered health status of adolescents, both physical (recovery, metabolism, growth, weight control) and cognitive (learning, memory, decision-making, vigilance). Therefore, the purpose of this work was to explore the effect of physical activity and nutrition on sleep among these two distinct adolescent populations. Altered sleep pattern in young athletes seems to be more related to sport constraints such as competition and travel. However, acute exercise improves sleep duration in quality in both populations (athlete and with obesity). Moreover, dietary intake seems to be a promising alternative to improve sleep quality. Only three days under controlled feeding fixed at the recommended dietary allowance resulted in reduced sleep onset latency in adolescents with obesity compared to ad-libitum condition. Finally, randomized controlled studies are needed to support the effect of certain nutrients on sleep. PROTMORPHEUS study will bring a fuller understanding of the effect of protein tryptophan/large neutral amino acids ratio on sleep.
... estrogen receptor signaling, and thus can directly or indirectly reduce cellular proliferation through estrogen receptor mediated signaling, thus bringing about downregulation/ inhibition of estrogen mediated proliferation of breast cancer cells (Fig. 7). However, remarkable contribution of melatonin towards cancer prevention is not only through attenuating the modulation of circadian rhythm but also through free-radical scavenging and antioxidant potential through multiple cell-protecting signaling cascades (Blask, 2009;Kaczor, 2010;Liu et al., 2018). Reduction in tumor size in breast cancer patients has also been previously (Kaczor, 2010) attributed to the inhibition of insulin-like growth factor. ...
Article
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Objective Compelling evidence from epidemiological and experimental studies indicate that the disruption of circadian rhythm and decreased melatonin synthesis are risk factors for breast cancer. With the ever-increasing rate of breast cancer cases globally, there is a strong need for safer, effective, and alternate treatment strategies with lesser side effects. This study aimed to investigate the effects of melatonin and vitamin D3 on the gene expression of two apoptotic factors, BCL-2 and Bax, in the MCF-7 cancer cell line. Methods Cell viability (MCF-7) was studied through MTT reduction assay in response to melatonin (1 nM, 5 nM and 10 nM) and vitamin D3 (0.5 nM, 1 nM and 10 NM). The optimum dose of melatonin (5 nM) and vitamin D3 (0.5 nM) were selected for their combination and Bax/BCL-2 ratio determination. Changes on the expression of genes BCL-2 and Bax, were determined through mRNA expression while Western blot analysis was used to detect changes in the expression of BCL-2 and Bax at the protein level. Results There was an upregulation of Bax gene expression and protein expression with the treatments of melatonin, vitamin D3, and their combination, with concomitant downregulation of Bcl-2 gene and protein expression. The Bax/BCL-2 ratio was increased significantly (p < 0.001) suggesting potential therapeutic treatments. Conclusion The results suggest that treatment with melatonin and vitamin D3 inhibits the proliferation and induced apoptosis in breast cancer cells. We report here for the first time that this combination has effectively activated Bax and downregulated BCL-2 at the DNA and protein level.
... In addition, SD could activate the hypothalamic-pituitary-adrenal axis to promote the release of glucocorticoids and promote the secretion of melatonin (37).Melatonin could shorten sleep latency and prolong sleep duration to promote sleep and regulate immune response. Considering that melatonin could simultaneously treat sleep deprivation and its inflammation, further studies about melatonin as a potential drug for the treatment of sleep deprivation were needed (38)(39)(40). ...
Article
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Sleep disturbance is common in patients with cancer and is associated with poor prognosis. However, the effects of sleep deprivation (SD) on immune surveillance during the development of hepatocellular carcinoma (HC) and the underlying mechanisms are not known. This was investigated in the present study using mouse models of SD and tumorigenesis. We determined that acute and chronic sleep deprivation (CSD) altered the relative proportions of various immune cell types in blood and peripheral organs. CSD increased tumor volume and weight, an effect that was enhanced with increasing CSD time. Expression of the cell proliferation marker Ki-67 was elevated in tumor tissues, and tumor cell infiltration into adjacent muscles was enhanced by CSD. Multicolor flow cytometry analysis revealed that CSD significantly reduced the numbers of antitumor CD3 ⁺ T cells and natural killer (NK) cells and increased that of immunosuppressive CD11b ⁺ cells infiltrating into the tumor microenvironment from the spleen via the peripheral blood. These results indicate that CSD impairs immune surveillance mechanisms and promotes immunosuppression in the tumor microenvironment to accelerate tumor growth, underscoring the importance of alleviating sleep disturbance in HC patients in order to prevent HC progression.
... Additionally, sleep disturbances related to LAN, can be compared to night shift work, which is an established risk factor for breast cancer (Touitou et al., 2017) and classified as "probably carcinogenic to humans" by the International Agency for Research on Cancer (IARC Monograph Working Group, 2019). Knowledge of the cancer inhibitory effect of melatonin, animal studies involving breast tumour xenografts, and sleep disturbance mechanisms known from night shift work literature all provide plausibility for an association between LAN and breast cancer (Blask, 2009;Hill et al., 2015;Xiang et al., 2019). Epidemiological evidence on LAN and breast cancer was reported in three cohort studies (Hurley et al., 2014;James et al., 2017;Xiao et al., 2020) and three case-control studies (Bauer et al., 2013;Garcia-Saenz et al., 2018;Ritonja et al., 2020), which used satellite-based data and images from the International Space Station (ISS) to estimate outdoor LAN as a proxy of personal exposure. ...
Article
Background Knowledge of the role of melatonin, xenograft experiments, and epidemiological studies suggests that exposure to light at night (LAN) may disturb circadian rhythms, possibly increasing the risk of developing breast cancer. Objectives We examined the association between residential outdoor LAN and the incidence of breast cancer: overall and subtypes classified by estrogen (ER) and progesterone (PR) receptor status. Methods We used data on 16,941 nurses from the Danish Nurse Cohort who were followed-up from the cohort baseline in 1993 or 1999 through 2012 in the Danish Cancer Registry for breast cancer incidence and the Danish Breast Cancer Cooperative Group for breast cancer ER and PR status. LAN exposure data were obtained from the U.S. Defense Meteorological Satellite Program (DMSP) available for 1996, 1999, 2000, 2003, 2004, 2006, and 2010 in nW/cm2/sr unit, and assigned to the study participants’ residence addresses during the follow-up. Time-varying Cox regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LAN and breast cancer, adjusting for individual characteristics, road traffic noise, and air pollution. Results Of 16,941 nurses, 745 developed breast cancer in total during 320,289 person-years of follow-up. We found no association between exposure to LAN and overall breast cancer. In the fully adjusted models, HRs for the highest (65.8-446.4 nW/cm2/sr) and medium (22.0-65.7 nW/cm2/sr) LAN tertiles were 0.97 (95% CI: 0.77, 1.23) and 1.09 (95% CI: 0.90, 1.31), respectively, compared to the lowest tertile of LAN exposure (0-21.9 nW/cm2/sr). We found a suggestive association between LAN and ER-breast cancer. Conclusion This large cohort study of Danish female nurses suggests weak evidence of the association between LAN and breast cancer incidence.
... Sleep deficiency has been also linked to higher adiposity, metabolic syndrome and type II diabetes that may in turn further increase the risk of cancer [56][57][58] . Furthermore, short sleep duration might be related to increased light-at-night exposure and thus lower nocturnal melatonin levels 38 , a hormone with well-known direct and indirect oncostatic properties 59,60 . Finally, sleep loss and/or circadian misalignment may be associated with gut microbiota disruption and subsequent increased risk for metabolic disease and CRC 61,62 . ...
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Sleep duration is a novel and potentially modifiable risk factor for cancer. We evaluated the association of self-reported sleep duration and daytime napping with odds of colorectal and gastric cancer. We included 2008 incident colorectal cancer cases, 542 gastric cancer cases and 3622 frequency-matched population controls, recruited in the MCC-Spain case–control study (2008–2013). Sleep information, socio-demographic and lifestyle characteristics were obtained through personal interviews. Multivariable adjusted logistic regression models were used to estimate odds ratios (OR) with 95% confidence intervals (CI) for cancer, across categories of sleep duration (≤ 5, 6, 7, 8, ≥ 9 hours/day), daytime napping frequency (naps/week) and duration (minutes/nap). Compared to 7 hours of sleep, long sleep was associated with increased odds of colorectal (OR ≥9 hours : 1.59; 95%CI 1.30–1.94) and gastric cancer (OR ≥9 hours : 1.95; 1.37–2.76); short sleep was associated with increased odds of gastric cancer (OR ≤5 hours : 1.32; 0.93–1.88). Frequent and long daytime naps increased the odds of colorectal (OR 6–7 naps/week, ≥30 min : 1.32; 1.14–1.54) and gastric cancer (OR 6–7 naps/week, ≥30 min : 1.56; 1.21–2.02). Effects of short sleep and frequent long naps were stronger among participants with night shift-work history. Sleep and circadian disruption may jointly play a role in the etiology of colorectal and gastric cancer.
... Sleep is increasingly acknowledged as a "vital sign" -a signal of health (or lack thereof) across multiple body systems (Grandner & Malhotra, 2015). Although the full extent of its purpose is a mystery, we know that sleep serves a critical role in brain function, learning and memory, metabolism, and immune function (Adamantidis & de Lecea, 2008;Blask, 2009;Czeisler & Gooley, 2007;Horne, 1985;Kyriacou & Hastings, 2010). Sleep is particularly important for youth during key developmental stages when brain and body are rapidly changing (Acebo & Carskadon, 2002;Blumberg, 2014;Colrain & Baker, 2011;Jenni & Carskadon, 2007;Sadeh et al., 2000;Simola, Laitalainen, et al., 2012;Wolfson & Carskadon, 1998). ...
Article
Background: Sleep is vital to youth well-being and when it becomes disturbed - whether due to environmental or individual factors - mental and physical health suffer. Sleep problems can also be a symptom of underlying mental health disorders. Assessing different components of sleep, including quality and hygiene, can be useful both for identifying mental health problems and for measuring changes in well-being over time. However, there are dozens of sleep-related measures for youth and it can be difficult to determine which to select for a specific research or clinical purpose. The goal of this review was to identify sleep-related measures for clinical and/or research use in youth mental health settings, and to update the evidence base on this topic. Method: We generated a list of candidate measures based on other reviews and searched in PubMed and PsycINFO using the terms "sleep" AND (measure OR assessment OR questionnaire) AND (psychometric OR reliability OR validity). Search results were limited to studies about children and adolescents (aged 2-17) published in English. Additional criteria for inclusion were that there had to be at least three publications reporting on the measure psychometrics in community or mental health populations. Sleep measures meeting these criteria were evaluated using the criteria set by De Los Reyes and Langer (2018). Results: Twenty-six measures, across four domains of sleep - insomnia, sleep hygiene, sleepiness, sleep quality - met inclusion criteria. Each measure had at least adequate clinical utility. No measure(s) emerged as superior across psychometric domains. Conclusion: Clinicians and researchers must evaluate sleep measures for each use case, as the intended purpose will dictate which measure is best. Future research is necessary to evaluate measure performance in transdiagnostic mental health populations, including youth with serious mental illness.
... Meanwhile, melatonin can modulate estrogen metabolism and also interrupt the signaling pathways of ER-mediated and is considered to protect against breast cancer (Cos et al., 2006). Melatonin can also suppress the proliferation and invasion of tumor cell, inhibit DNA damage, and modulate the immune system to add eradication of tumor cells, all of which may suppress the development of breast cancer (Blask, 2009;Cohen et al., 1978). Furthermore, other mechanisms should be also acknowledged as discussed by Veiga et al. (2019), such as melatonin blocks estrogen receptors binding to DNA and transactivation functions (Madaeva et al., 2017), has antioxidant and anti-angiogenic actions, and also induces apoptosis in tumors (Ajith, 2015;Madaeva et al., 2017). ...
Article
Recent epidemiological studies have explored effects of light at night (LAN) exposure on breast cancer, but reported inconsistent findings. We performed a systematic review and meta-analysis of available evidence regarding the association of LAN assessed by satellite data with breast cancer. We conducted a systematic PubMed, Web of Science, and EMBASE database literature search until August 2020. Random-effects meta-analysis was applied to synthesis risk estimates. Heterogeneity was measured using statistics of Cochran’s Q, I2, and Tau2 (τ2). We assessed publication bias through funnel plot and Egger’s test. Moreover, subgroup analyses according to study design and menopausal status were performed. Risk of bias (RoB) of each included study was assessed using a domain-based RoB assessment tool. The confidence in the body of evidence was appraised using the GRADE approach for level-of-evidence translation. A total of 1157 studies were identified referring to LAN and breast cancer, from which 6 were included for quantitative synthesis. We found a significantly higher odds of breast cancer in the highest versus the lowest category of LAN exposure (OR = 1.11, 95% CI: 1.06, 1.16; I2 = 0.0%). In the subgroup analyses stratified by menopausal status and study design, significant association was found in postmenopausal women (OR = 1.07, 95% CI = 1.00, 1.13) and cohort studies (OR = 1.11, 95% CI = 1.05, 1.18), while the summary estimates of premenopausal women and case-control studies showed no significance. The level of evidence for the association of LAN exposure and breast cancer risk was graded as “moderate” with “probably low” RoB according to the NTP/OHAT framework. In conclusion, this study suggests a link of LAN exposure with risk of breast cancer. Further high-quality prospective studies, especially performed in low-to middle-income countries with improvement in the area of LAN exposure assessment are needed to advance this field.
... However, the nocturnal secretion of melatonin can be modified by multiple medications or light exposure, leading to an alteration in the function of the body clock, usually with detrimental effects on health [81]. Indeed, a decreased melatonin production has been associated with an increased risk of cancer [82,83]. Nonetheless, exogenous melatonin can be used to treat desynchronization and circadian disorders [84], and to promote sleep [85], due to its chronobiotic and hypnotic effects. ...
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Opinion statement Sleep and circadian rhythm disturbance are among the most commonly experienced symptoms in patients with cancer. These disturbances occur throughout the spectrum of cancer care from diagnosis, treatment, and long into survivorship. The pathogenesis of these symptoms and disturbances is based on common inflammatory pathways related to cancer and its’ treatments. The evaluation of sleep and circadian disorders requires an understanding of how these symptoms cluster with other cancer-related symptoms and potentiate each other. A thorough evaluation of these symptoms and disorders utilizing validated diagnostic tools, directed review of clinical information, and diagnostic testing is recommended. Treatment of sleep and circadian disturbance in cancer patients should be based on the findings of a detailed evaluation, including specific treatment of primary sleep and circadian disorders, and utilize integrative and personalised management of cancer-related symptoms through multiple pharmacologic and non-pharmacologic modalities. Recognition, evaluation, and treatment of sleep and circadian rhythm disturbance in cancer may lead to improved symptom management, quality of life, and outcomes.
... Sleep disorders can have extensive adverse effects both physically and mentally; for example, they can promote obesity and impair cognition (Espie, 2002;Wang et al., 2014;André et al., 2019). They are also listed as IARC Group 2A carcinogens, and a number of epidemiological and clinical studies have found that multiple sleep disorders significantly increase the risk of cancer (Davis et al., 2001;Schernhammer et al., 2003;Blask, 2009). Sleep fragmentation (SF) is a common type of sleep disorder generally caused by obstructive sleep apnea (Young et al., 2002); to some extent, it significantly increases the cancer incidence and mortality in younger patients (Campos-Rodriguez et al., 2013;Martínez-García et al., 2014), and this effect has been confirmed in animal experiments (Cao et al., 2015). ...
Article
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Ganoderma lucidum (Lingzhi) polysaccharide peptide (GL-pp) is a component of the globally acknowledged traditional Chinese medicine Ganoderma lucidum; Ganoderma lucidum is known for its sedative, hypnotic, immune regulatory, antitumor, and other pharmacological effects. In recent years, sleep disorders have been linked to many diseases and human body disorders, including cancer. Some experimental studies in mice found that sleep fragmentation could promote tumor development and progression. However, effects on GL-pp on tumor metastasis under circumstances of sleep disorders have rarely been studied. Thus, in this study, we used mice with sleep fragmentation (SF) bearing B16-F10-luc-G5 melanoma tumors to investigate the effect of SF on melanoma metastasis. Furthermore, we investigated the antitumor and antimetastatic effects of GL-pp (80 mg/kg) in mice suffering from SF and bearing B16-F10-luc-G5. Then, whole proteomics was used to analyze the differences in protein expression in the lung tissue between SF mice bearing B16-F10-luc-G5 with and without GL-pp administration. High-throughput pyrosequencing of 16S rRNA was also used to analyze the impact of GL-pp on the gut microbiota composition in SF mice bearing B16-F10-luc-G5. Last, the effects of GL-pp on macrophage polarization and TNF-α serum levels were detected. Collectively, we found that SF significantly facilitated the B16-F10-luc-G5 melanoma tumor metastasis in mice, while GL-pp significantly reduced B16-F10-luc-G5 melanoma tumor metastasis under the condition of SF, in which proteomics and gut microbiota had been changed greatly.
... Shorter sleep means a greater possibility of nighttime activities and a greater chance of exposure to light at night, subsequently resulting in decreased melatonin levels [83]. Melatonin plays an anti-cancer role experimentally by suppressing the initial phase of cell proliferation and stimulating differentiation and apoptosis, whereas decreased or insufficient melatonin may promote tumor growth [83,84]. Furthermore, melatonin is intricately linked with sex hormone levels [31]. ...
Article
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Purpose To collect existing evidence on the relationship between sleep duration and health outcomes. Methods A thorough search was conducted in PubMed, Web of Science, Embase, and the Cochrane Database of Systematic Reviews from inception to January, 2021. Meta-analyses of observational and interventional studies were eligible if they examined the associations between sleep duration and human health. Results In total, this umbrella review identified 69 meta-analyses with 11 outcomes for cancers and 30 outcomes for non-cancer conditions. Inappropriate sleep durations may significantly elevate the risk for cardiovascular disease (CVD), cognitive decline, coronary heart disease (CHD), depression, falls, frailty, lung cancer, metabolic syndrome (MS), and stroke. Dose–response analysis revealed that a 1-h reduction per 24 hours is associated with an increased risk by 3–11% of all-cause mortality, CHD, osteoporosis, stroke, and T2DM among short sleepers. Conversely, a 1-h increment in long sleepers is associated with a 7–17% higher risk of stroke mortality, CHD, stroke, and T2DM in adults. Conclusion Inappropriate sleep duration is a risk factor for developing non-cancer conditions. Decreasing and increasing sleep hours towards extreme sleep durations are associated with poor health outcomes.
... Insomnia problems are approximately three times higher among cancer patients than in the general population [23,82,83], and impaired sleep patterns persist in more than 50% of BC survivors due to the multiorgan component of the disease, the deterioration of the immune system, or the alteration in melatonin release, among other factors [13,[25][26][27]82,[84][85][86][87][88]. In this way, it has been suggested that the relationship between night work and sleep rhythm disruption in nurses implies an increased risk of BC [17,89] and could also involve exposure to other risk factors such as stress, self-medication, tobacco abuse, or the use of psychoactive substances [23]. ...
Article
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Night work has been highlighted by the International Agency for Research on Cancer (IARC) as a likely carcinogenic factor for humans, associated with breast cancer and professions that require continuity of work. Knowing the impact that short and long-term night work has on the nurses’ collective seems a priority, therefore, this study aims to analyse the relationship between night work and the development of breast cancer risk factors in nurses. For this, a cross-sectional study through an online questionnaire on breast cancer risk variables and working life was designed. The study was conducted in Spain and the sample consisted of 966 nurses, of whom 502 were healthy participants and 56 were breast cancer patients. These two groups were compared in the analyses. A descriptive analysis was performed, and the relationship was tested using χ2 independence test and OR calculation. The CHAID (Chi Square Automatic Interaction Detection) data mining method allowed for the creation of a segmentation tree for the main risk variables. The most significant risk variables related to working life have been the number of years worked, nights worked throughout life, and years working more than 3 nights per month. Exceeding 16 years of work has been significant for women and men. When the time worked is less than 16 years, the number of cases increases if there is a family history of cancer and if there have been more than 500 nights of work. High-intensity night work seems more harmful at an early age. The accumulation of years and nights worked increase the risk of breast cancer when factors such as sleep disturbance, physical stress, or family responsibilities come together.
... Such sleep-related characteristics of patients with cancer reduce immune functioning (Firth et al., 2017a) and elicit changes in carbohydrate metabolism and endocrine function (Spiegel et al., 1999). Further, they slow their recovery and exacerbate the disorder (Blask, 2009). Increased pain sensitivity (Sateia and Lang, 2008), fatigue, depression levels (Donovan and Jacobsen, 2007), and reduced quality of life (Simon and Vonkorff, 1997) also frequently arise due to sleeprelated problems. ...
Article
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Objective: This pilot study aimed to evaluate the efficacy of a digital cognitive behavioral therapy (dCBT) in patients with cancer experiencing sleep problems. Methods: A total of 57 participants aged 25-65 years (6M/51F with a mean of 42.80 years and a standard deviation of 14.15 years) were randomly assigned to three groups-21 participants to a dCBT program (HARUToday Sleep), 20 participants to an app-based attentional control program (HARUCard Sleep), and 16 participants to a waitlist control group-and evaluated offline before and after the program completion. Of the 57 participants, there were a total of 45 study completers, 15 participants in each group. The dependent variables were sleep quality scores, measured by the Pittsburgh Sleep Quality Index (PSQI) and health-related quality of life scores, measured using the Short-Form 36 (SF-36), and attentional bias scores from a dot-probe computer task. Results: For both the intention-to-treat (N = 57) and study-completers analyses (N = 45, 15 for each group), a significant increase supported by a large effect size was found in the quality of sleep score of the HARUToday Sleep group compared to both the app-based attentional control and the waitlist control group. However, no significant changes were found in the quality of life and attentional bias scores. Conclusion: Our results suggest that the HARUToday Sleep app has the potential to serve as an intervention module to enhance the sleep quality of patients with cancer experiencing sleep problems.
... The Light at night (LAN) hypothesis states that the exposure to visible light during night, lowers the nocturnal melatonin production by the pineal gland which in turn increases the risk of cancer development due to melatonin anti-proliferative effects and melatonin enhancement of the immune system [29][30][31][32] . Predictions of this hypothesis which include among others (increased breast cancer risk among non-day shift workers, blindness lower risk, and co-distribution between population level community nighttime and breast cancer incidence) 29,30 are supported by increasing evidence. ...
Article
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Polymorphisms in the PER3 gene have been associated with several human disease phenotypes, including sleep disorders and cancer. In particular, the long allele of a variable number of tandem repeat (VNTR) polymorphism has been previously linked to an increased risk of breast cancer. Here we carried out a combined germline and somatic genetic analysis of the role of the PER3 VNRT polymorphism in breast cancer. The combined data from 8284 individuals showed a non-significant trend towards increased breast cancer risk in the 5-repeat allele homozygous carriers (OR = 1.17, 95% CI: 0.97–1.42). We observed allelic imbalance at the PER3 locus in matched blood and tumor DNA samples, showing a significant retention of the long variant (risk) allele in tumor samples, and a preferential loss of the short repetition allele ( p = 0.0005). Gene co-expression analysis in healthy and tumoral breast tissue samples uncovered significant associations between PER3 expression levels with those from genes which belong to several cancer-associated pathways. Finally, relapse-free survival (RFS) analysis showed that low expression levels of PER3 were linked to a significant lower RSF in luminal A ( p = 3 × 10 ⁻¹² ) but not in the rest of breast cancer subtypes.
... [20] Melatonin has been demonstrated to suppress the initiation phase of tumorigenesis and inhibit the proliferation of human cancer cell lines in experimental studies. [21,22] Another hypothesis is that impaired immune function may underlie the link between sleep loss and carcinogenesis. [23] In previous studies among poor sleepers, we found that the changes in sleep duration may suppress immune function and change the balance of cytokine production. ...
Article
Background: Prospective analyses have yet to identify a consistent relationship between sleep duration and the incidence of gastrointestinal (GI) cancers. The effect of changes in sleep duration on GI cancer incidence has scarcely been studied. Therefore, we aimed to examine the association between baseline sleep duration and annual changes in sleep duration and GI cancer risk in a large population-based cohort study. Methods: A total of 123,495 participants with baseline information and 83,511 participants with annual changes in sleep duration information were prospectively observed from 2006 to 2015 for cancer incidence. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and their confidence intervals (CIs) for GI cancers according to sleep duration and annual changes in sleep duration. Results: In baseline sleep duration analyses, short sleep duration (≤5 h) was significantly associated with a lower risk of GI cancer in females (HR: 0.31, 95% CI: 0.10-0.90), and a linear relationship between baseline sleep duration and GI cancer was observed (P = 0.010), especially in males and in the >50-year-old group. In the annual changes in sleep duration analyses, with stable category (0 to -15 min/year) as the control group, decreased sleep duration (≤-15 min/year) was significantly associated with the development of GI cancer (HR: 1.29; 95% CI: 1.04-1.61), especially in the >50-year-old group (HR: 1.32; 95% CI: 1.01-1.71), and increased sleep duration (>0 min/year) was significantly associated with GI cancer in females (HR: 2.89; 95% CI: 1.14-7.30). Conclusions: Both sleep duration and annual changes in sleep duration were associated with the incidence of GI cancer.
... Existing literature have established the effects of physical activity (1,2), screen time (3,4), and sleep duration (5,6) on the depression status of both, adolescent and adult populations. Moreover, previous studies revealed that unhealthy time use activities (e.g., excessive sedentary time, inadequate sleep duration) were risk predictors of physiological diseases, including cardiovascular diseases (7)(8)(9), hypertension (10,11), and cancers (12)(13)(14). Based on plentiful existing evidence, the World Health Organization (WHO) and other health institutes proposed updated time use guidelines to direct people's daily activities for substantial health benefits (15)(16)(17)(18). ...
Article
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Background To date, the relationship between diverse time use behaviors and depression status among emerging adults have not been disentangled in the literature. Therefore, if and how the time displacement mechanism activates depressive symptoms among emerging adults remains unclear. Methods To fill this gap in the literature, we employed a network analysis to make estimations. The emerging adult sample ( N = 1,811) was collected by the Guizhou Population Health Cohort Study. Time use behaviors were measured by an adaption of the self-administered International Physical Activity Questionnaire, and depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9). Results The results revealed that the time displacement mechanism of emerging adults differed from that of adolescents. Sleep duration was not crowded out by other activities, while the time spent on computer use was found to be negatively related to time spent on heavy work activities. Moreover, computer use behavior triggered three depressive symptoms (“Anhedonia,” “Guilt,” and “Motor”), but inhibited “Suicide.” The results of the directed acyclic graph revealed that females and heavy drinkers were at risk of depression. Limitations The study sample was confined to only one province, which may limit its generalizability. The cross-sectional design impeded the ability to draw causal inferences. Conclusion Our results enhance the current understanding of the internal mechanism of how time use behaviors influence depressive symptoms among emerging adults.
... Nocturnal melatonin secretion can persists in constant darkness, but exposure to light during the nighttime can suppress the release of the hormone into the bloodstream (25). The endogenous activity of the central clock results in melatonin production, so suppression of melatonin can lead to stimulation of cancer development (27). The possibility of chronotherapy and melatonin supplementation can be applied as a new platform to enhance the efficacy of chemotherapy drugs through precise time-dependent administration (28). ...
Article
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The circadian system is an innate clock mechanism that governs biological processes on a near 24-hour cycle. Circadian rhythm disruption (i.e., misalignment of circadian rhythms), which results from the lack of synchrony between the master circadian clock located in the suprachiasmatic nuclei (SCN) and the environment (i.e., exposure to day light) or the master clock and the peripheral clocks, has been associated with increased risk of and unfavorable cancer outcomes. Growing evidence supports the link between circadian disruption and increased prevalence and mortality of genitourinary cancers (GU) including prostate, bladder, and renal cancer. The circadian system also plays an essential role on the timely implementation of chronopharmacological treatments, such as melatonin and chronotherapy, to reduce tumor progression, improve therapeutic response and reduce negative therapy side effects. The potential benefits of the manipulating circadian rhythms in the clinical setting of GU cancer detection and treatment remain to be exploited. In this review, we discuss the current evidence on the influence of circadian rhythms on (disease) cancer development and hope to elucidate the unmet clinical need of defining the extensive involvement of the circadian system in predicting risk for GU cancer development and alleviating the burden of implementing anti-cancer therapies.
... The influence of neuro-endocrine signals on proliferation of immune cells or the last effector mechanism as production of antibodies or the activity of cytotoxic cells were estimated in previous studies (13,14), Each of the main stress system hypothalamo pituitary adrenal(HPA) axis and the sympathetic nervous system(SNS), during nocturnal sleep period their activity inhibited, associated with suppression in cortisol and catecholamines in circulation (13,15), In normal nocturnal sleep cytokine production will support towards type1 dominance and therefore reinforce proinflammatory activity and showed that the nocturnal prevalence of type1 cytokines shifted towards type2 cytokines by acute experimental sleep deprivation that's mean sleep leads to direct suppression of IL-10 production as anti-inflammatory cytokines (16). The pituitary growth hormone (GH), prolactin and the pineal hormone melatonin that responsible about cell growth, differentiation and restoration that's during sleep show an increase in their blood levels (17), that promote activation of immune cells and enhance production of pro-inflammatory cytokines as interleukin IL-12,tumor necrotic factor alpha TNF-α (18)(19)(20). Where these proinflammatory cytokines found to be peak throughout nocturnal sleep (21,22). ...
Article
Full-text available
Sleep is a naturally, restorative process, characterized by altered consciousness. Normal sleep and circadian system act as important physiological regulator on immune functions, these regulation mediated by neurotransmitters, hormones and cytokines signals which support relation between the immune system and central nervous system. Various immune parameters in peripheral circulation show Diurnal changes over the day, these changes under effect of the 2 main stress systems, the sympathetic nervous system(SNS) and the hypothalamo pituitary adrenal (HPA) axis, changes occurring in immune parameters over the 24-h during the sleep-wake cycle categorized to nocturnal Proinflammatory and daytime anti-inflammatory activity. In addition to its effects on cognitive function, compelling evidence links sleep loss to alterations in the neuroendocrine, immune and inflammatory systems. sleep deprivation either in partial sleep deprivation or total sleep deprivation as a stressful status enhances the adrenergic tons that affects innate and adaptive immunity, with increasing susceptibility to infections and immune-related diseases. Several studies have shown negative effects of sleep deprivation on all functions of the body and its effect on the immune system this review aims to explain the changes occurring in immune parameters and inflammatory cytokines over the 24-h during the normal sleep-wake cycle and during sleep disturbance and benefit of sleep recovery(napping) to recede these physiological changes that resulting from sleep deprivation. ÖZET Uyku değişen bilinç durumlarıyla karakterize onarıcı ve doğal bir süreçtir. Uyku ve sirkadiyen sistem bağışıklık sistemi fonksiyonları üzerinde güçlü bir düzenleyici etkiye sahiptir. Bu etki bağışıklık sistemi ve merkezi sinir sistemi arasındaki ilişkiyi destekleyen nörotransmitterler, hormonlar ve sitokinler aracılığıyla oluşturulur. Çeşitli bağışıklık sistemi parametreleri gün içerisinde kan dolaşımında diurnal değişiklikler göstermektedir. Bu değişiklikler hipotalamus-hipofiz-adrenal (HPA) aks ve sempatik sinir sisteminin (SNS) kontrolündedir. Gün boyunca uyku-uyanıklık döngüsünde, bağışıklık sistemi parametrelerinde gerçekleşen değişiklikler, gece pro-inflamatuar etki gündüz ise anti-inflamatuar etki olarak ortaya çıkmaktadır. Uyku eksikliği bilişsel işlev üzerindeki etkilerine ek olarak, nöroendokrin, bağışıklık ve inflamatuar sistemdeki değişikliklere de yol açmaktadır. Kısmi ya da tam uyku yoksunluğu stresli bir durum olarak sempatik tonusu arttırmasıyla doğal ve kazanılmış bağışıklığı etkilemektedir. Bu durum enfeksiyonlara yatkınlığa ve bağışıklık sistemiyle ilişkili hastalıklarda artışa sebep olmaktadır. Çeşitli araştırmalar, uyku yoksunluğunun vücudun tüm işlevleri üzerindeki olumsuz etkilerini ve bağışıklık sistemi üzerindeki etkilerini göstermiştir. Bu derleme gün içerisinde normal uyku-uyanıklık dönemi ya da uyku bozukluğu sırasında, bağışıklık sistemi parametreleri ve inflamatuar sitokinlerdeki değişiklikleri; uyku açığını kapatmak için yapılan toparlanma uykusunun, uyku yoksunluğunun sebep olduğu fizyolojik değişiklikleri geriletme üzerindeki faydalarını açıklamayı amaçlamaktadır.
... The influence of neuro-endocrine signals on proliferation of immune cells or the last effector mechanism as production of antibodies or the activity of cytotoxic cells were estimated in previous studies (13,14), Each of the main stress system hypothalamo pituitary adrenal(HPA) axis and the sympathetic nervous system(SNS), during nocturnal sleep period their activity inhibited, associated with suppression in cortisol and catecholamines in circulation (13,15), In normal nocturnal sleep cytokine production will support towards type1 dominance and therefore reinforce proinflammatory activity and showed that the nocturnal prevalence of type1 cytokines shifted towards type2 cytokines by acute experimental sleep deprivation that's mean sleep leads to direct suppression of IL-10 production as anti-inflammatory cytokines (16). The pituitary growth hormone (GH), prolactin and the pineal hormone melatonin that responsible about cell growth, differentiation and restoration that's during sleep show an increase in their blood levels (17), that promote activation of immune cells and enhance production of pro-inflammatory cytokines as interleukin IL-12,tumor necrotic factor alpha TNF-α (18)(19)(20). Where these proinflammatory cytokines found to be peak throughout nocturnal sleep (21,22). ...
Article
Full-text available
Sleep is a naturally, restorative process, characterized by altered consciousness. Normal sleep and circadian system act as important physiological regulator on immune functions, these regulation mediated by neurotransmitters, hormones and cytokines signals which support relation between the immune system and central nervous system. Various immune parameters in peripheral circulation show Diurnal changes over the day, these changes under effect of the 2 main stress systems, the sympathetic nervous system(SNS) and the hypothalamo pituitary adrenal (HPA) axis, changes occurring in immune parameters over the 24-h during the sleep-wake cycle categorized to nocturnal Proinflammatory and daytime anti-inflammatory activity. In addition to its effects on cognitive function, compelling evidence links sleep loss to alterations in the neuroendocrine, immune and inflammatory systems. sleep deprivation either in partial sleep deprivation or total sleep deprivation as a stressful status enhances the adrenergic tons that affects innate and adaptive immunity, with increasing susceptibility to infections and immune-related diseases. Several studies have shown negative effects of sleep deprivation on all functions of the body and its effect on the immune system this review aims to explain the changes occurring in immune parameters and inflammatory cytokines over the 24-h during the normal sleep-wake cycle and during sleep disturbance and benefit of sleep recovery(napping) to recede these physiological changes that resulting from sleep deprivation. ÖZET Uyku değişen bilinç durumlarıyla karakterize onarıcı ve doğal bir süreçtir. Uyku ve sirkadiyen sistem bağışıklık sistemi fonksiyonları üzerinde güçlü bir düzenleyici etkiye sahiptir. Bu etki bağışıklık sistemi ve merkezi sinir sistemi arasındaki ilişkiyi destekleyen nörotransmitterler, hormonlar ve sitokinler aracılığıyla oluşturulur. Çeşitli bağışıklık sistemi parametreleri gün içerisinde kan dolaşımında diurnal değişiklikler göstermektedir. Bu değişiklikler hipotalamus-hipofiz-adrenal (HPA) aks ve sempatik sinir sisteminin (SNS) kontrolündedir. Gün boyunca uyku-uyanıklık döngüsünde, bağışıklık sistemi parametrelerinde gerçekleşen değişiklikler, gece pro-inflamatuar etki gündüz ise anti-inflamatuar etki olarak ortaya çıkmaktadır. Uyku eksikliği bilişsel işlev üzerindeki etkilerine ek olarak, nöroendokrin, bağışıklık ve inflamatuar sistemdeki değişikliklere de yol açmaktadır. Kısmi ya da tam uyku yoksunluğu stresli bir durum olarak sempatik tonusu arttırmasıyla doğal ve kazanılmış bağışıklığı etkilemektedir. Bu durum enfeksiyonlara yatkınlığa ve bağışıklık sistemiyle ilişkili hastalıklarda artışa sebep olmaktadır. Çeşitli araştırmalar, uyku yoksunluğunun vücudun tüm işlevleri üzerindeki olumsuz etkilerini ve bağışıklık sistemi üzerindeki etkilerini göstermiştir. Bu derleme gün içerisinde normal uyku-uyanıklık dönemi ya da uyku bozukluğu sırasında, bağışıklık sistemi parametreleri ve inflamatuar sitokinlerdeki değişiklikleri; uyku açığını kapatmak için yapılan toparlanma uykusunun, uyku yoksunluğunun sebep olduğu fizyolojik değişiklikleri geriletme üzerindeki faydalarını açıklamayı amaçlamaktadır.
... Chronic sleep insufficiency is reported to cause systemic low-grade inflammation in the body, which is one of the known provocatory factors for malignancy and cancer [61]. Also, melatonin which is known to decrease cancer development, particularly breast cancer, is suppressed in short sleepers [73]. A study conducted on 23,620 middle-aged participants showed an increased risk of cancer onset by almost 43% after a mean follow up of 7.8 years in those suffering from sleep insufficiency (<6 h/d) [46]. ...
Chapter
Almost all organisms have sleep time. In humans, about one third of life is spent in sleeping or trying to fall asleep. Obtaining the standard sleep in each of the life periods is of crucial importance. Adequate duration, good quality, appropriate timing and regularity, along with absence of any associated sleep disorders are the main features of a standard sleep. Genes, gender, and age mainly determine the sleep needs. Sleep is essential for the proper functioning of multiple body organs and systems; thus, its problems will adversely affect nearly all body organs. These adverse health consequences depend on the chronicity of the problem, age, and type of the sleep disturbance. It seems that the adverse effects following sleep disturbances are more prominent in the brain in younger population, i.e., children and adolescents, while adults and older ages experience more chronic diseases. In addition to increasing mortality, sleep problems have short- and long-term impact on increasing the risk of several chronic disorders including cardiovascular diseases, metabolic syndrome, obesity, type 2 diabetes, hormonal imbalances, cognitive and mental health problems, cancer, osteoporosis, and stroke. In the present chapter, we will first briefly explain the mechanisms of sleep regulation and the characteristics of a standard sleep. Then, we will summarize the importance and benefits of a life-course healthy sleep, as well as acute and chronic adverse health effects of sleep disturbances.
... One of the consequences of light pollution is the negative impact it has on mammal animals [6,7], insects [8,9] and human health. Studies have shown a link between light pollution, disturbed human biorhythms, and increased numbers of patients with certain cancers, particularly breast and colon cancer [10,11]. It is shown that the proportion of patients with direct exposure to artificial light from unsuitable lighting systems is higher if they are exposed to it during typical sleep times and/or when working night shifts. ...
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The improper illumination of cultural heritage buildings and monuments can be a source of enormous light pollution, which can have a major impact on the overall environment of the illuminated area. Such lighting can be the result of carelessness or a poorly designed lighting system. This paper presents one of the methodologies that can significantly reduce light pollution, especially spilt light out of building façades. The methodology is based on using luminaires with specially made shutters and an appropriate silhouette of the object. The shutters are designed with the help of photos of the object and the location’s sizes measured. The methodology was tested during the renovation of the lighting systems of different churches in Slovenia and is described using the example of the Church of St. Thomas near Ptuj, Slovenia (N46°28.9554′, E16°0.7416′). The results show that the methodology is effective and can significantly reduce light pollution that occurs when such buildings are incorrectly lit.
... This questionnaire is a 7item self-report, and it is a 5-point Likert scale (0 = no problem; 4 = very severe problem), and the outcome score ranges from 0 to 28. The overall yielding score is elucidated as follows: (0-7) refers to the absence of insomnia, (8)(9)(10)(11)(12)(13)(14) interprets sub-threshold insomnia; (15)(16)(17)(18)(19)(20)(21) refers to moderate insomnia, and lastly (22)(23)(24)(25)(26)(27)(28) refers to severe insomnia. In addition to that, the data of participants' sociodemographic include average age, gender, different levels of residency, marital status, and the number of on-call per month. ...
... Unfortunately, we could not disentangle whether the observed association was due to the antitumor effect of melatonin or the benefit from good quality sleep. Available evidence suggests that a higher level of melatonin in the blood associates with sleep propensity during the night, but the association seems not being causal (49). Results from healthy human subjects and rat models suggested that sleep deprivation and exposure to a constant light environment did not suppress melatonin serum levels despite their associations with the disruption of the melatonin rhythms (50,51). ...
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Introduction: Preclinical evidence suggests that melatonin may affect cellular pathways involved in colorectal cancer (CRC). We sought to test whether melatonin use was associated with decreased risk of CRC using population-based data. Methods: We performed a nationwide cohort study using a new-user study design. We identified a total of 58,657 incident melatonin users aged 50 years and older from the Prescribed Drug Register, and matched them with 175,971 comparisons who did not use melatonin, on the ratio of 1:3. The Cox regression model was used to calculate hazard ratios and 95% confidence intervals. Results: The incidence rate of CRC was 10.40 per 10,000 person-years for melatonin users, whereas the rate was 12.82 per 10,000 person-years in the nonusers. We found a significant negative association between melatonin use and risk of CRC (adjusted hazard ratio, 0.82; 95% confidence interval, 0.72-0.92). A test for trend showed a significant dose-response correlation (P < 0.001). The decrease of CRC risk was independent of tumor location and stage at diagnosis. When stratified by age groups, the inverse association was significant only among individuals aged 60 years and older. Discussion: This population-based cohort study suggests that the use of melatonin was associated with a reduced risk of CRC. Further studies are needed to confirm the observed association and to explore the underlying mechanisms.
... Because sleep behaviors might affect each other 25 , for example, late chronotype and insomnia might result in shorter sleep duration and excessive daytime sleepiness, these sleep behaviors might individually act through different mechanisms, but could work synergistically to increase the risk of fracture. For instance, insomnia and abnormal sleep duration were relevant to the metabolic disruption (e.g., decreased melatonin secretion) 26 , and activated inflammation 27 , which might increase the risk of fracture 28,29 . Late chronotype had been linked to disrupted circadian rhythm 30,31 , and the deficiency of clock gene (e.g., BMAL1) in mice could result in a low bone mass 32 . ...
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We combined conventional evidence from longitudinal data in UK Biobank and genetic evidence from Mendelian randomization (MR) approach to infer the causality between sleep behaviors and fracture risk. We found that participants with insomnia showed 6.4% higher risk of fracture (hazard ratio [HR] = 1.064, 95% CI = 1.038–1.090, P = 7.84 × 10 ⁻⁷ ), falls and bone mineral density (BMD) mediated 24.6% and 10.6% of the intermediary effect; the MR analyses provided the consistent evidence. A U-shape relationship was observed between sleep duration and fracture risk ( P < 0.001) with the lowest risk at sleeping 7–8 h per day. The excessive daytime sleepiness and “evening” chronotype were associated with fracture risk in observational study, but the association between chronotype and fracture did not show in MR analyses. We further generated a sleep risk score (SRS) with potential risk factors (i.e., insomnia, sleep duration, chronotype, and daytime sleepiness). We found that the risk of fracture increased with an increasing SRS (HR = 1.087, 95% CI = 1.065–1.111, P = 1.27 × 10 ⁻¹⁴ ). Moreover, 17.4% of the fracture cases would be removed if all participants exhibited a healthy sleep pattern. In conclusion, insomnia had a causal effect on fracture, falls had a larger intermediary effect than BMD in this association. Individuals with fracture risk could benefit from the intervention on unhealthy sleep pattern.
... A cohort study confirmed that insomnia increases the risk of respiratory tract infection, and it has been reported that patients receiving chemotherapy are more susceptible to infection if they complain of insomnia [77,78]. Many researchers have long believed that insomnia increases the risk of cancer [79]. This is not just a belief; some studies have reported that insomnia increases the risk of breast cancer [80,81]. ...
Article
Sleep plays a critical role in homeostasis of the body and mind. Insomnia is a disease that causes disturbances in the initiation and maintenance of sleep. Insomnia is known to affect not only the sleep process itself but also an individual's cognitive function and emotional regulation during the daytime. It increases the risk of various neuropsychiatric diseases such as depression, anxiety disorder, and dementia. Although it might appear that insomnia only affects the nervous system, it is also a systemic disease that affects several aspects of the body, such as the cardiovascular, endocrine, and immune systems; therefore, it increases the risk of various diseases such as hypertension, diabetes mellitus, and infection. Insomnia has a wide range of effects on our bodies because sleep is a complex and active process. However, a high proportion of patients with insomnia do not seek treatment, which results in high direct and indirect costs. This is attributed to the disregard of many of the negative effects of insomnia. Therefore, we expect that understanding insomnia as a systemic disease will provide an opportunity to understand the condition better and help prevent secondary impairment due to insomnia.
... Poor sleep quality, a public health issue with a prevalence of 31.8-60% in adults [1][2][3][4], has been associated with increased disease risk, including obesity [5], hypertension [6,7], diabetes mellitus [8], cardiovascular diseases [9][10][11], mental health problems [12], and neurodegenerative diseases [13,14], and motor injuries [15]. Therefore, an improved understanding of modifiable risk factors is critical to public health. ...
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Objective To investigate the relationship between secondhand smoke (SHS) exposure and sleep quality in never-smokers of Northwest China.Methods Never-smoking adults (≥ 15 years) from Xinjiang, Northwest China, were included in this cross-sectional survey between April and October 2019. SHS exposure in never-smokers was estimated using a structured questionnaire. Sleep quality was evaluated by Pittsburgh Sleep Quality Index (PSQI), with PSQI score > 5 classified as poor sleep quality. Association of SHS exposure and frequency and duration of SHS exposure with poor sleep quality were analyzed by using a multivariate logistic regression after adjusting for potential confounding factors, including stratification by sex.ResultsThe mean age of participants was 48.0 years, and 77% were females. Of 21,198 never-smokers, 13% (n = 2703) reported SHS exposure and 35% (n = 7390) reported poor sleep quality. In multivariate logistic regression analysis, a significant association was observed between SHS exposure and poor sleep quality (adjusted odds ratio (OR), 1.36; 95% confidence interval (CI) 1.24–1.48). Subgroup analysis showed a negative association of SHS exposure with sleep quality in both sexes. However, a significant dose–response relationship of frequency and duration of SHS exposure per week with poor sleep quality was observed only in females. Consistent results were also observed in the aged ≥ 18 years.Conclusion Exposure to SHS is associated with poor sleep quality in never-smoking adults of Northwest China. A dose–response relationship between SHS exposure and poor sleep quality is found in women. Avoiding SHS exposure may have beneficial effects on sleep quality, especially for females.
Article
Sleep duration is emerging as an important modifiable risk factor for morbidity and mortality. We assessed the association between sleep duration and cancer incidence and mortality among Japanese adults using data from six population-based cohorts with 271 694 participants. During a total follow-up period of about 5.9 million person-years, we identified 40 751 incident cancer cases and 18 323 cancer deaths. We computed study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models and pooled the estimates using random-effects meta-analysis. Sleep duration of ≥ 10 h (vs. 7 h) was associated with increased risk of cancer incidence among women (HR 1.19, 95% CI 1.02-1.38), but not men, and increased risk of cancer mortality among men (HR 1.18, 95% CI 1.00-1.39) and women (HR 1.44, 95% CI 1.20-1.73). Sleep duration of ≤ 5 h (vs. 7 h) was not associated with cancer incidence and mortality. However, among post-menopausal women, sleep durations of both ≤ 5 h and ≥ 10 h (vs. 7 h) were associated with an increased risk of cancer mortality. Among Japanese adults, sleep duration of ≥ 10 h is associated with increased risk of cancer incidence and mortality among women and cancer mortality among men.
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Background: Evidence on the variability of associations between sleep duration and incident disability according to the presence or absence of sleep complaints is limited.This study assessed the associations between sleep durations and disability incidence stratified by the presence or absence of sleep complaints. Methods: A total of 3,896 community-dwelling Japanese adults aged ≥65 years were observed for 37 months after the self-reporting of sleep duration and sleep complaints. Disability incidence was defined by the certification of needed support/long-term care according to the public long-term care insurance. A proportional hazards model was fitted to examine the association of sleep duration with incident disability according to the presence or absence of fatigue on awakening. Missing values of covariates were estimated using multiple imputations. Results: Long sleep duration was associated significantly with incident disability regardless of the presence or absence of fatigue on awakening; the age- and sex-adjusted hazard ratios were 1.62 (95% Confidence Interval, 1.02–2.56) and 1.35 (1.04–1.75), respectively. The elevated risks of long sleep durations without complaints disappeared after an adjustment for impairments of functional health, while that of long sleep duration with complaints disappeared after an adjustment for medical histories, especially stroke history. Conclusion: Long sleep duration was associated with disability incidence among community-dwelling older persons. The domains of health accounting for the association differed by the presence or absence of sleep complaints.
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Background: It is unclear which psychological factors (stressors, emotional correlates, and psychophysiological markers) induce cancer risk. This currently limits the potential for prevention strategies. Purpose: The aim of this review is to bring forth evidence of stress as a determinant of cancer risk from a public health perspective, written for a broad public of practitioners and scientists. Methods: Based on a semisystematic literature search, the impact of different aspects/types of stress and the potential physiological and behavioral pathways are summarized, while highlighting further research, public health and clinical implications. Results: Between 2007 and 2020, 65 case-control or cohort studies have been identified. Apart from overall cancer (N = 24), 12 cancer types have been associated with psychological stress with most for breast (N = 21), colorectal (N = 11) and lung/prostate/pancreas cancer (N = 8 each). Although the evidence regarding the mechanisms is still scarce, cancer development in relation to stress might be due to interacting and combined effects of different stress(or) types, but such interaction has not really been tested yet. The path from stress towards cancer incidence consists of a biological pathway with endocrinology and immunology as well as stress-induced behavioral pathways, including smoking, alcoholism, sleep disruption, an unhealthy diet, and low physical activity together with the related phenomenon of obesity. Conclusion: Not only the stress but also the stress-induced lifestyle should be targeted for cancer prevention and treatment. Future research should include a more diverse spectrum of cancer types (not only hormonal related like breast cancer) and of stress measures while also considering behavioral covariates.
Article
Background The relationship between insomnia and lung cancer is scanty. The Mendelian randomization approach provides the rationale for evaluating the potential causality between genetically-predicted insomnia and lung cancer risk. Methods We extracted 148 insomnia-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from published genome-wide association studies (GWASs). Summary data of individual-level genetic information of participants were obtained from the International Lung Cancer Consortium (ILCCO) (29,266 cases and 56,450 controls). MR analyses were performed using the inverse-variance-weighted approach, MR pleiotropy residual sum and outlier (MR-PRESSO) test, weighted median estimator, and MR-Egger regression. Sensitivity analyses were further performed using Egger intercept analysis, leave-one-out analysis, MR-PRESSO global test, and Cochran's Q test to verify the robustness of our findings. Results The results of the MR analysis indicated an increased risk of lung cancer in insomnia patients (OR = 1.1671; 95% CI 1.0754–1.2666, p = 0.0002). The subgroup analyses showed increased risks of lung adenocarcinoma (OR = 1.1878; 95% CI 1.0594–1.3317, p = 0.0032) and squamous cell lung cancer (OR = 1.1595; 95% CI 1.0248–1.3119, p = 0.0188). Conclusion Our study indicated that insomnia is a causal risk factor in the development of lung cancer. Due to the lack of evidence on both the epidemiology and the mechanism level, more studies are needed to better elucidate the results of the study.
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This chapter will focus on Ayurveda and yoga to understand the power of the mind and body to resolve conflict. The fundamental principles of Ayurveda will be discussed in relation to the universe and body because we are a microcosm of the macrocosm. A society so rich in science, pharmaceuticals, and healthcare professionals still struggles for good health. Society continues to remain malnourished even though overfed with food causing the human mind to turn to other modalities like Ayurveda and yoga. As contemporary medicine starts with disease, Ayurveda begins with health with the focus on maintaining the health of the healthy. The fundamental principles of Ayurveda regarding the biological humors (doshas) will be discussed in relation to the five elements of ether, air, fire, water, earth. The main focus will be diet and lifestyle. This chapter will provide pearls of Ayurvedic wisdom to allow one to assimilate these practices into daily life.
Article
Background context The clinical symptoms of cervical myelopathy (CM) are closely associated with the risk factors of sleep disturbance, and its pathophysiological process is similar to that of spinal cord injury. Therefore, patients with CM are also expected to have sleep disturbance like patients with spinal cord injury, who typically have various types of sleep disorders. Fortunately, sleep disturbance in patients with CM is expected to respond well to treatment, and clinical studies are required to establish proper treatment strategies for CM patients with sleep disturbance. Purpose To compare the effects of CM treatment on sleep quality between patients treated surgically and those managed conservatively and to identify predictors associated with sleep improvement. Study design/setting Prospective cohort study Patient sample Patients diagnosed as having CM Outcome measures Pittsburgh Sleep Quality Index (PSQI) Methods The effect of CM treatment on sleep improvement at the 6-month follow-up was evaluated using a multivariate logistic regression analysis of propensity score-matched patients. To investigate factors associated with significant sleep improvement, a subgroup analysis was performed. Results A total of 131 patients with CM and sleep disturbance were enrolled. Among these patients, 31 received surgical treatment and 100 received conservative treatment. Sleep quality improved rapidly and consistently after surgery, and significant sleep improvement was observed in most of the patients in the surgical group (26/31 patients, 83.9%) at the 6-month follow-up. However, sleep improvement only occurred in 27 (27%) of the 100 patients in the conservative group at the 6-month follow-up. The subgroup analysis revealed that the degree of CM determined by mJOA scores > 13 was a significant predictor of sleep improvement after conservative treatment. Conclusions Clinicians should closely monitor patients with CM with sleep disturbance, and proper treatment strategies should be considered according to the severity of the conditions.
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Background: Urgent restlessness is a common condition following ketamine anesthesia in the emergency. The aim of this study was to compare the effects of intravenous midazolam, oral melatonin, and placebo in controlling of ketamine-induced agitation in adult patients undergoing minor emergency surgery. Methods: In a randomized clinical trial study, 96 patients in the emergency department who needed ketamine for sedation were divided into three groups of 32 cases. Prior to administration of ketamine, the first group received intravenous midazolam plus oral placebo, the second group received intravenous placebo and oral melatonin, and the third group received oral placebo plus intravenous placebo. The time of re-consciousness and recovery time were determined and compared in the three groups. Findings: The mean score of restlessness was significantly lower in the midazolam and melatonin groups than in the control group (P = 0.020); but there was no difference between the midazolam and melatonin groups (P > 0.999). Conclusion: According to the findings of the study, oral melatonin, as intravenous as midazolam, appears to be effective in reducing ketamine-induced agitation in anesthesia for minor emergency surgeries.
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The circadian rhythm, sleep, and cancer are complex phenomena that demonstrate a dynamic interrelationship through regulation of and moderation by overlapping molecular, physiologic, and psychological processes. These relationships vary based on cancer subtype, thus broad generalizations are difficult. While additional research is needed to understand the specific mechanisms of coregulation, these processes provide an opportunity to improve care for cancer patients. In this article, we explore the current understanding of the basic and clinical science linking these phenomena and provide a foundation for the care of circadian and sleep problems in cancer patients.
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Introduction Melatonin levels are partially driven by the parenchyma volume of the pineal gland. Low urinary levels of 6‐sulfatoxymelatonin have been associated with increased risk of advanced prostate cancer, but the relationship between pineal gland volume and composition and prostate cancer risk has not been examined. Materials and Methods We utilized data from 864 men from the AGES‐Reykjavik Study with complete pineal gland volumes and urinary 6‐sulfatoxymelatonin measurements. Pineal parenchyma, calcification, and cyst volumes were calculated from brain magnetic resonance imaging. Levels of 6‐sulfatoxymelatonin were assayed from prediagnostic urine samples. We calculated Pearson correlation coefficients between parenchyma volume and urinary 6‐sulfatoxymelatonin levels. We used Cox proportional hazards regression to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) comparing prostate cancer risk across parenchyma volume tertiles and across categories factoring in parenchyma volume, gland composition, and urinary 6‐sulfatoxymelatonin level. Results Parenchyma volume was moderately correlated with urinary 6‐sulfatoxymelatonin level (r = .24; p < .01). There was no statistically significant association between parenchyma volume tertile and prostate cancer risk. Men with high parenchyma volume, pineal cysts and calcifications, and low urinary 6‐sulfatoxymelatonin levels had almost twice the risk of total prostate cancer as men with low parenchyma volume, no pineal calcifications or cysts, and low urinary 6‐sulfatoxymelatonin levels (HR: 1.98; 95% CI: 1.02, 3.84; p: .04). Conclusions Although parenchyma volume is not associated with prostate cancer risk, pineal gland composition and other circadian dynamics may influence risk for prostate cancer. Additional studies are needed to examine the interplay of pineal gland volume, composition, and melatonin levels on prostate cancer risk.
Article
The present study is aimed at probing the molecular interaction between Carmustine (anti-cancer drug) and Melatonin (hormone) within the realm of Density functional theory at B3LYP/6-31G (d,p) level, and using vibrational spectroscopic techniques, namely, FTIR (400–4000 cm–1), Raman (145–3560 cm–1) and surface-enhanced Raman spectroscopy (SERS) (145–3560 cm–1) techniques as well. The vibrational spectra are assigned for both monomers and the interacting complex incorporating the VEDA program and found to be consistent with the experimental findings. NBO analysis has been performed to explore the charge transfer path between Carmustine and Melatonin that provides a reliable insight into the origin of N–H∙∙∙O intermolecular hydrogen bond, which is further supported by the MEP analysis. The complex's thermodynamic and quantum chemical parameters are computed and compared to the respective values of the individual states. The biomolecular complex is found to have low HOMO-LUMO gap and high hyper-polarizability values indicating the complex to be high chemical reactivity and nonlinear optical activity. Moreover, molecular docking analysis is performed to investigate the pharmaceutical activeness of the complex against the selected MIA protein.
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Objectives To examine the effects of qigong interventions on sleep disturbance-related symptom clusters for cancer patients and to explore the possible mediating role of fatigue and depression in affecting sleep. Methods In this systematic review and meta-analysis, a systematic search was conducted through October 2020 by searching multiple English and Chinese databases. Inclusion was limited to randomized controlled trials that measured the effect of qigong on sleep and fatigue/depressive symptoms in cancer patients. Eleven studies involving 907 cancer patients were included in the systematic review, whereas the meta-analysis included ten studies with 851 cancer patients. Results The most commonly investigated form of qigong was Taichi, and the intervention length ranged from 10 days to 6 months. All studies employed self-reported measurements. Overall, qigong significantly improved sleep (SMD = -1.28, 95% CI: -2.01, -0.55) and fatigue (SMD = -0.89, 95% CI: -1.59, -0.19) in cancer patients post-intervention, but not depressive symptoms (SMD = -0.69, 95% CI: -1.81, 0.42). Notably, the benefits on sleep and fatigue became non-significant after 3 months. Qigong’s effect on sleep was significantly mediated by its effect on fatigue (β = 1.27, SE = 0.24, p = 0.002), but not depressive symptoms (β = 0.53 SE = 0.26 p = 0.106). Conclusions Qigong can be recommended for improving sleep disturbance-fatigue symptom clusters in the cancer population, while qigong’s benefit on sleep is likely based on its effect on reducing fatigue. Future qigong studies should adopt more rigorous design and employ strategies to maintain longevity of intervention benefits.
Article
Background Prolonged sleep is a higher stroke risk, but post-stroke prolonged sleep facilitates stroke recovery. No study has explored the relationship between pre- and post-stroke prolonged sleep and their involvement in stroke-related quality of life (QOL). This study aimed to clarify the role of pre- and post-stroke prolonged sleep in QOL and sleep quality during hospitalization. Methods Fifty-one subacute stroke inpatients were enrolled. QOL was assessed by the Stroke and Aphasia QOL Scale-39-J. Sleep quality and lifestyle values were assessed by original questionnaires. Results Patients in pre-stroke prolonged sleep > 8 h had a higher incidence of post-stroke poor sleep quality than those belonging to the normal or shorter hours (OR 5.33, 95% CI 1.30–21.84, p = 0.047). In addition, pre-stroke prolonged sleep was associated with lower scores of psychosocial QOL and lifestyle values of “accepting disability; caring about what other people think of what you do”. In contrast, post-stroke prolonged sleep was associated with the lower risk of post-stroke poor sleep quality (OR 0.27, 95% CI 0.08–0.86, p = 0.045). Post-stroke high sleep quality had higher (better) scores of physical and energy QOL, and lifestyle values of “caring about what other people think of what you do; having some places to go out after discharge” compared with post-stroke poor sleep quality. Post-stroke prolonged sleep was derived from pre-stroke not prolonged sleep rather than pre-stroke prolonged sleep (p = 0.039, Chi-square test). Conclusions Pre-stroke prolonged sleep is associated with a higher incidence of post-stroke poor sleep quality and lower scores of QOL and lifestyle values after stroke.
Article
Working at night causes circadian disruption and it has been classified as a probable carcinogen. An evening chronotype, or preference for late day activity, has been shown to increase risk for several adverse health effects, such as metabolic disorders and recently, breast cancer. To further explore this emerging area of interest, we examined the association between endometrial cancer (EC) risk, another common cancer in women, and chronotype. The women in this study were members of the California Teachers Study cohort, which was established in 1995. Chronotype was reported on a subsequent questionnaire (Q5), administered in 2012-2013. The women included in this analysis were under age 90 years, were post-menopausal at Q5, and had no hysterectomy. The cancer cases, identified through linkages to the California Cancer Registry, were diagnosed between 1996 and 2014. We used unconditional logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between chronotype and EC diagnosis. There were 437 EC cases and 26,753 cancer-free controls included in this analysis. Controls were more likely to classify themselves as current morning chronotypes than were cases (39% and 34%, respectively). Compared to morning types, women who were definite evening types had a statistically significantly elevated OR of 1.44 (95% CI 1.09-1.91). This association was more pronounced among obese women as compared to non-obese women. For evening type compared to morning type, the OR among obese women was 2.01 (95% CI 1.23, 3.29) while the OR for non-obese women was 1.12 (95% CI 0.77, 1.63). To our knowledge, the association between EC risk and evening chronotype has not been previously reported, but is consistent with the small body of literature which suggests increased breast cancer risks among evening chronotypes. Because this study was based on a retrospective analysis in a cohort of mostly white female teachers in California, further analysis of chronotype as a potential EC risk factor should be considered in other cohorts and in prospective analyses in order to further explore this relationship.
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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.
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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."
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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.
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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.
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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.
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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.
Data
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.
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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.
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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.
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• 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.
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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.
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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).
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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.
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(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.
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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.
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.
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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.
Article
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.
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.