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ABSTRACT Chrononutrition is a branch of chronobiology that evaluates nutrients and the pathways implicated in their regulation in accordance with circadian rhythms. Sleep deprivation and disturbances have been strongly associated with the progression of different metabolic alterations, and the time of food intake plays a fundamental role in maintaining metabolic homeostasis. It has been demonstrated that not only the components of food are important, but quantity and quality are also crucial elements of a healthy eating pattern. Chrononutrition is an emerging tool that could help improve dietary interventions beyond those derived from consuming an adequate amount of each nutrient. Diabetes is a complex endocrine pathology characterized by sustained hyperglycemia. Dietary changes are a key component in obtaining adequate control and preventing long-term complications. Recent studies emphasize the use of chrononutrition and its components as a novel dietary intervention that could improve metabolic control. The use of chrononutrition as a dietary intervention is faced with challenges such as the presence of gaps in the literature that limit its implementation. This emphasizes the imperative need for additional research that can lead to an evidence-based use of this intervention. (Rev Invest Clin. 2024;76(2):80-90)

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Chrononutrition is a branch of chronobiology that evaluates nutrients and the pathways implicated in their regulation in accordance with circadian rhythms. Sleep deprivation and disturbances have been strongly associated with the progression of different metabolic alterations, and the time of food intake plays a fundamental role in maintaining metabolic homeostasis. It has been demonstrated that not only the components of food are important, but quantity and quality are also crucial elements of a healthy eating pattern. Chrononutrition is an emerging tool that could help improve dietary interventions beyond those derived from consuming an adequate amount of each nutrient. Diabetes is a complex endocrine pathology characterized by sustained hyperglycemia. Dietary changes are a key component in obtaining adequate control and preventing long-term complications. Recent studies emphasize the use of chrononutrition and its components as a novel dietary intervention that could improve metabolic control. The use of chrononutrition as a dietary intervention is faced with challenges such as the presence of gaps in the literature that limit its implementation. This emphasizes the imperative need for additional research that can lead to an evidence-based use of this intervention.

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Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also for important determinants of clinical outcome. In this review, we provide a comprehensive overview of the interplay between chronobiology and cerebrovascular disease. We discuss circadian regulation of pathophysiological mechanisms underlying stroke onset or tolerance as well as in vascular dementia. This includes cell death mechanisms, metabolism, mitochondrial function, and inflammation/immunity. Furthermore, we present clinical evidence supporting the link between disrupted circadian rhythms and increased susceptibility to stroke and dementia. We propose that circadian regulation of biochemical and physiological pathways in the brain increase susceptibility to damage after stroke in sleep and attenuate treatment effectiveness during the active phase. This review underscores the importance of considering circadian biology for understanding the pathology and treatment choice for stroke and vascular dementia and speculates that considering a patient's chronotype may be an important factor in developing precision treatment following stroke.

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Tauopathies, a group of neurodegenerative diseases that includes Alzheimer's disease, commonly lead to disturbances in sleep-wake patterns and circadian rhythm disorders. The circadian rhythm, a recurring 24-hour cycle governing human biological activity, is regulated by the hypothalamic suprachiasmatic nucleus (SCN) and endogenous transcriptional-translational feedback loops. Surprisingly, little attention has been given to investigating tauopathy-driven neuropathology in the SCN and the repercussions of SCN and circadian gene dysfunction in the human brain affected by tauopathies. This review aims to provide an overview of the current literature on the vulnerability of the SCN in tauopathies in humans. Emphasis is placed on elucidating the neuronal and glial changes contributing to the widespread disruption of the molecular circadian clock. Furthermore, this review identifies areas of knowledge requiring further investigation.

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Sleep regularity is an essential part of the multidimensional sleep health framework. The phenomenon of irregular sleep patterns is widespread in contemporary lifestyles. This review synthesizes clinical evidence to summarize the measures of sleep regularity and discusses the role of different sleep regularity indicators in developing cardiometabolic diseases (coronary heart disease, hypertension, obesity, and diabetes). Existing literature has proposed several measurements to assess sleep regularity, mainly including the standard deviation (SD) of sleep duration and timing, sleep regularity index (SRI), interdaily stability (IS), and social jetlag (SJL). Evidence on associations between sleep variability and cardiometabolic diseases varies depending on the measure used to characterize variability in sleep. Current studies have identified a robust association between SRI and cardiometabolic diseases. In comparison, the association between other metrics of sleep regularity and cardiometabolic diseases was mixed. Meanwhile, the associations of sleep variability with cardiometabolic diseases differ across the population. SD of sleep characteristics or IS may be more consistently associated with HbA1c in patients with diabetes compared with the general population. The association between SJL and hypertension for patients with diabetes was more accordant than in the general population. Interestingly, the age-stratified association between SJL and metabolic factors was observed in the present studies. Furthermore, the relevant literature was reviewed to generalize the potential mechanisms through which irregular sleep increases cardiometabolic risk, including circadian dysfunction, inflammation, autonomic dysfunction, hypothalamic-pituitary-adrenal (HPA) axis disorder, and gut dysbiosis. Health-related practitioners should give more attention to the role of sleep regularity on human cardiometabolic in the future.

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BACKGROUND AND AIMS: Melatonin is a pineal hormone that plays an important role as an endogenous synchronizer of circadian rhythms and energy metabolism. As this circadian component has been closely related to eating behavior, an important question on this topic would be whether melatonin administration could influence eating habits. However, this topic has been rarely studied in the literature in individuals with excessive weight and chronic circadian misalignment, such as shift workers. Therefore, the present study aims to evaluate the effects of exogenous melatonin administration on the quali/quantitative aspects and temporal distribution of food intake in female night workers with excessive weight (overweight and obesity). An additional aim is to evaluate the association of the referred outcomes with circadian misalignment and chronotype. METHODS: A randomized, double-blind, placebo-controlled, crossover clinical trial was conducted with 27 female nursing professionals with excessive weight who worked permanent night shifts. The protocol was implemented under real-life conditions for 24 weeks, in two randomly allocated conditions (12 weeks of melatonin and 12 weeks of placebo). The quali/quantitative aspects of food intake (NOVA classification, total energy intake and the proportion of calories from macronutrients) and meal timing were assessed using food diaries. Timing for every meal recorded in the diaries was assessed to evaluate the temporal distribution of food intake. Generalized estimating equations were performed for each dependent variable. RESULTS: No significant modifications in total energy intake, macronutrient distribution, types of foods consumed, and meal timing were observed after melatonin administration. Different levels of circadian misalignment and chronotype did not interfere with these results. CONCLUSION: Eating habits of female night workers with excessive weight remained unchanged after melatonin administration, and no association of these results with circadian misalignment and chronotype was found. These results suggest that the metabolic effects of melatonin may occur independently of food intake.

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The COVID-19 lockdown has had a significant impact on people's lives worldwide. This study aimed to investigate the effect of personality on chrononutrition during the COVID-19 lockdown. Using a cross-sectional design, a convenient sample of 543 adults in Qatar completed an online questionnaire using validated tools to assess personality and chrononutrition behaviors during the first COVID-19 lockdown. Participants scoring high in openness were more likely to eat at night (mean difference (MD) = 0.41, 95% confidence interval (CI): 0.10, 0.72) compared to those scoring high in agreeableness, while those scoring high in extraversion and openness had a shorter eating window (MD = -76.6, 95%CI: -146.3, -6.93 and MD = -29.8, 95%CI: -56.5, -3.01, respectively). Participants high in extraversion had longer evening latency (MD = 66.3, 95%CI: 25.4, 107.3) and evening eating (MD = -62.0, 95%CI: -114.0, -9.0) compared those high in agreeableness. Participants high in conscientiousness showed evidence of first eating event misalignment during the weekend (MD = 22.0, 95%CI: 0.15, 43.9) and last eating event misalignment during weekdays (MD = -27.8, 95%CI: -47.3, -8.41) compared to those high in agreeableness. Lastly, participants high in openness showed evidence of eating window misalignment during the weekend (MD = 30.6, 95%CI: 5.01, 56.2). This study suggests that personality traits can inform personalized nutritional approaches when aiming for healthy habits during unexpected periods, such as the COVID-19 pandemic.

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BACKGROUND: Blood pressure (BP) variability is an independent risk factor for cardiovascular events. Recent evidence supports a role for the gut microbiota in BP regulation. However, whether the gut microbiome is associated with BP variability is yet to be determined. Here, we aimed to investigate the interplay between the gut microbiome and their metabolites in relation to BP variability. METHODS: Ambulatory BP monitoring was performed in 69 participants from Australia (55.1% women; mean±SD, 59.8±7.26 years; body mass index, 25.2±2.83 kg/m2). These data were used to determine nighttime dipping, morning BP surge (MBPS) and BP variability as SD. The gut microbiome was determined by 16S ribosomal RNA (rRNA) sequencing and metabolite levels by gas chromatography. RESULTS: We identified specific taxa associated with systolic BP variability, nighttime dipping, and MBPS. Notably, Alistipesfinegoldii and Lactobacillus spp. were only present in participants within the normal ranges of BP variability, MBPS and dipping, while Prevotella spp. and Clostridium spp., were found to be present in extreme dippers and the highest quartiles of BP SD and MBPS. There was a negative association between MBPS and microbial α-diversity (r=-0.244, P=0.046). MBPS was also negatively associated with plasma levels of microbial metabolites called short-chain fatty acids (r=-0.305, P=0.020), particularly acetate (r=-0.311, P=0.017). CONCLUSIONS: Gut microbiome diversity, levels of microbial metabolites, and the bacteria Alistipesfinegoldii and Lactobacillus were associated with lower BP variability and Clostridium and Prevotella with higher BP variability. Thus, our findings suggest the gut microbiome and metabolites may be involved in the regulation of BP variability.

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A variety of organisms including mammals have evolved a 24h, self-sustained timekeeping machinery known as the circadian clock (biological clock), which enables to anticipate, respond, and adapt to environmental influences such as the daily light and dark cycles. Proper functioning of the clock plays a pivotal role in the temporal regulation of a wide range of cellular, physiological, and behavioural processes. The disruption of circadian rhythms was found to be associated with the onset and progression of several pathologies including sleep and mental disorders, cancer, and neurodegeneration. Thus, the role of the circadian clock in health and disease, and its clinical applications, have gained increasing attention, but the exact mechanisms underlying temporal regulation require further work and the integration of evidence from different research fields. In this review, we address the current knowledge regarding the functioning of molecular circuits as generators of circadian rhythms and the essential role of circadian synchrony in a healthy organism. In particular, we discuss the role of circadian regulation in the context of behaviour and cognitive functioning, delineating how the loss of this tight interplay is linked to pathological development with a focus on mental disorders and neurodegeneration. We further describe emerging new aspects on the link between the circadian clock and physical exercise-induced cognitive functioning, and its current usage as circadian activator with a positive impact in delaying the progression of certain pathologies including neurodegeneration and brain-related disorders. Finally, we discuss recent epidemiological evidence pointing to an important role of the circadian clock in mental health.

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PURPOSE: This study aimed to identify the predictors of depression among female rotating-shift nurses. DESIGN AND METHODS: This secondary data analysis used data of 190 Korean female rotating-shift nurses from the parent study conducted in 2018. A multiple logistic regression analysis was performed to identify the predictors of depression. FINDINGS: Young age, poor sleep quality, and greater morning-shift social jetlag predicted depression among female nurses working a three-shift schedule. PRACTICE IMPLICATIONS: Nursing management should consider scheduling shifts to minimize nurses' social jetlag and develop interventions for improving sleep quality to prevent depression among female rotating-shift nurses.

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BACKGROUND-PURPOSE: A bidirectional relationship appears to connect tension-type headache (TTH) and circadian dysregulation. The present systematic review examined the published evidence for melatonin (MT) supplementation in the prophylaxis of TTH. Initially, we reviewed case-control studies investigating nocturnal MT or 6-sulphatoxymelatonin (aMT6s, a urine-discarded metabolite) in TTH individuals and healthy controls (HC). Secondly, we reviewed studies appraising the use of MT in the prevention of TTH. METHODS: The search strategy involved MEDLINE EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar and OpenGrey. Case-control studies were appraised according to the Newcastle-Ottawa-Scale, whereas randomised controlled trials were assessed based on the risk-of-bias Cochrane tool. Infrequent, as well as frequent, episodic, and chronic TTH patients were evaluated separately in children and adults. RESULTS: Our search strategy yielded two case-control studies. One (high-quality) did not reveal any difference in morning salivary MT concentration between children with frequent episodic TTH and HC. The second (moderate-quality) was indicative of a disturbed nocturnal secretion pattern in adults with chronic TTH. For the second part, five uncontrolled studies were retrieved. In total, 94 adults with chronic TTH were assessed and results were suggestive of a beneficial effect of MT on headache frequency, intensity, induced disability, and induced analgesic consumption. However, the uncontrolled-unblinded designs may have induced an important placebo effect. Non-adult populations and frequent TTH were substantially understudied. CONCLUSIONS: There are not enough studies to designate the role of MT in the prevention of TTH. Given the disease's background, additional relevant research is warranted for chronic TTH.

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Noise-induced hearing loss is one of the major causes of acquired sensorineural hearing loss in modern society. While people with excessive exposure to noise are frequently the population with a lifestyle of irregular circadian rhythms, the effects of circadian dysregulation on the auditory system are still little known. Here, we disturbed the circadian clock in the cochlea of male CBA/CaJ mice by constant light (LL) or constant dark. LL significantly repressed circadian rhythmicity of circadian clock genes Per1, Per2, Rev-erbα, Bmal1, and Clock in the cochlea, whereas the auditory brainstem response thresholds were unaffected. After exposure to low-intensity (92 dB) noise, mice under LL condition initially showed similar temporary threshold shifts to mice under normal light-dark cycle, and mice under both conditions returned to normal thresholds after 3 weeks. However, LL augmented high-intensity (106 dB) noise-induced permanent threshold shifts, particularly at 32 kHz. The loss of outer hair cells (OHCs) and the reduction of synaptic ribbons were also higher in mice under LL after noise exposure. Additionally, LL enhanced high-intensity noise-induced 4-hydroxynonenal in the OHCs. Our findings convey new insight into the deleterious effect of an irregular biological clock on the auditory system.

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BACKGROUND: Nurses and midwives make up almost 50% of the global healthcare shift working workforce. Shift work interferes with sleep and causes fatigue with adverse effects for nurses' and midwives' health, as well as on patient safety and care. Where other safety-critical sectors have developed Fatigue Risk Management Systems, healthcare is behind the curve; with published literature only focussing on the evaluation of discreet sleep-related/fatigue-management interventions. Little is known, however, about which interventions have been evaluated for nurses and midwives. Our review is a critical first step to building the evidence-base for healthcare organisations seeking to address this important operational issue. OBJECTIVES: We address two questions: (1) what sleep-related/fatigue-management interventions have been assessed in nurses and midwives and what is their evidence-base? and (2) what measures are used by researchers to assess intervention effectiveness? DESIGN AND DATA SOURCES: The following databases were searched in November, 2018 with no limit on publication dates: MEDLINE, PsychINFO and CINAHL. REVIEW METHODS: We included: (1) studies conducted in adult samples of nurses and/or midwives that had evaluated a sleep-related/fatigue-management intervention; and (2) studies that reported intervention effects on fatigue, sleep, or performance at work, and on measures of attention or cognitive performance (as they relate to the impact of shift working on patient safety/care). RESULTS: The search identified 798 potentially relevant articles, out of which 32 met our inclusion criteria. There were 8619 participants across the included studies and all were nurses (88.6% female). We did not find any studies conducted in midwives nor any studies conducted in the UK, with most studies conducted in the US, Italy and Taiwan. There was heterogeneity both in terms of the interventions evaluated and the measures used to assess effectiveness. Napping could be beneficial but there was wide variation regarding nap duration and timing, and we need to understand more about barriers to implementation. Longer shifts, shift patterns including nights, and inadequate recovery time between shifts (quick returns) were associated with poorer sleep, increased sleepiness and increased levels of fatigue. Light exposure and/or light attenuation interventions showed promise but the literature was dominated by small, potentially unrepresentative samples. CONCLUSIONS: The literature related to sleep-related/fatigue-management interventions for nurses and midwives is fragmented and lacks cohesion. Further empirical work is warranted with a view to developing comprehensive Fatigue Risk Management Systems to protect against fatigue in nurses, midwives, and other shift working healthcare staff.

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Cluster headache (CH) has been associated with circadian disturbances. The present systematic review examined available evidence for the utilization of melatonin (MT) in CH prophylaxis. First, case-control studies assessing nocturnal MT or its urine-expelled metabolite 6-sulfatoxymelatonin (aMT6s) in CH individuals and healthy controls (HC) were reviewed and meta-analyzed. Secondly, the results from randomized controlled trials (RCTs) and non-randomized studies evaluating MT's use in the prevention of CH were discussed. Literature search included MEDLINE, EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar, and OpenGrey. Bouts and remissions were assessed separately. Ten case-control studies (adult participants) were retrieved. Seven evaluated serum MT; meta-analysis involved only three of them (due to deficient reporting, n: bout = 31, remission = 38, HC = 31). Results were compatible with lower nocturnal serum MT levels during bouts [bout-HC; FE-MD = -29.89 pg/mL, 95% CI = (-46.00, -13.78), remission-HC; FE-MD = -2.40 pg/mL, 95% CI = (-16.57, 21.38), bout-remission; RE-MD = -32.10 pg/mL, 95% CI = (-56.78, -7.42)]. Nocturnal urinary melatonin was appraised in two studies, but reporting issues impeded the capitalization of the results. Nocturnal urine aMT6s was evaluated by two studies (n: bout = 29, remission = 22, HC = 20), and pooled results were indicative of lower aMT6s concentration in CH individuals during both active and inactive periods [bout-HC; FE-MD = -9.63 µg/nocturnal urine collection, 95% CI = (-14.40, -4.85), remission-HC; FE-MD = -9.12 µg/nocturnal urine collection, 95% CI = (-14.63,-3.62), bout-remission; FE-MD = -0.58 µg/nocturnal urine collection, 95% CI = (-4.58, 3.42)]. Regarding CH prophylaxis, one RCT and two non-randomized trials were retrieved, involving a total of 41 adult CH individuals (11-episodic, 31-chronic) and rendering the deduction of any conclusions precarious. Overall, available data for the role use of MT in CH are insufficient and inconclusive. Complementary studies evaluating endogenous MT concentrations and MT administration to patients with CH are warranted.

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SARS-CoV-2/COVID-19 leads to numerous unplanned or natural experiments with health and disease. Physical (social) distancing - a counter-measure with no alternative, but with no precedence in scope and scale either - is a key intervention and trigger of natural experiments. From a practical perspective, concerned disciplines should increase awareness of, provide recommendations to meet, and develop research for, health challenges arising from physical distancing at home. From the field of chronobiology, prolonged home stays may place undue strain on the body's circadian timing system but straightforward and often underestimated advice for coping can be provided (herein we provide such advice). Of course, advice or recommendations from other concerned disciplines that identify challenges associated with current COVID-19 mitigation strategies are also needed. From a research perspective, different disciplines should rise to the occasion and explore unsuspected natural experiment angles toward novel insights to promote health and prevent disease.

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Understanding the health consequences of chronic disruption of circadian rhythms can contribute to improving prevention strategies for shift workers. Chronic circadian disruption in shift work has been linked to a higher risk of stroke. Dysregulated immune responses are also linked to circadian disruption and may be a factor in stroke outcomes in shift workers. In this study, we test the hypotheses that specific schedules of circadian disruption exacerbate inflammatory responses in the brain, causing an increase in infarct size after experimentally induced ischemic stroke. Mice were exposed to 1 of 5 different lighting schedules followed by a 30-min middle cerebral artery occlusion, then reperfusion and 3-day recovery. A history of weekly phase advances resulted in an increased infarct volume versus the control lighting schedule. These effects were shift-direction specific, nonpermanent, and required multiple shifts to occur. In a separate cohort, stereotaxic injections of lipopolysaccharide were given bilaterally after exposure to 1 of 3 different lighting schedules. Ratios of pro- to anti-inflammatory cytokine expression show dysregulated responses after a history of phase advances. We conclude that chronic circadian disruption leads to worsened stroke outcome in a direction- and schedule-specific manner likely because of priming of the inflammatory response in the brain. These pieces of evidence suggest that the health impacts of shift work may be improved by targeting shift work scheduling, inflammatory mediators, or both.

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BACKGROUND: Sleep disorders and circadian dysregulation appear to be associated with primary headache disorders. OBJECTIVE: The aim of this study was to review the existing evidence for the deployment of melatonin in migraine prophylaxis. Initially, case-control studies investigating nocturnal melatonin and 6-sulphatoxymelatonin (aMT6s, melatonin metabolite discarded by the urine) levels in patients with migraine and healthy controls (HC) would be reviewed and meta-analyzed. Second, results from randomized controlled trials (RCTs) and non-randomized studies evaluating the use of melatonin in migraine would be synthesized. METHODS: MEDLINE EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar, and OpenGrey were comprehensively searched. The quality of studies was assessed according to the Newcastle-Ottawa Scale (case-control studies) and the Risk-of-Bias Cochrane tool (RCTs). Random-effects (RE) or fixed-effects (FE) model was used based on heterogeneity among studies (homogeneity assumed when PQ > 0.1 and I2  < 30%). Publication bias was assessed by funnel plots. RESULTS: Literature search provided 11 case-control studies. Evidence was compatible with lower nocturnal serum [5 of 6 studies were synthesized due to deficient reporting of 1 abstract, migraine n = 197, HC n = 132, RE MD = -12.29 pg/ml, 95%CI = (-21.10, -3.49)] and urinary melatonin [3 studies, migraine n = 30, HC n = 29, RE MD = -0.12 nmol/nocturnal (12 hours) urinary collection, 95%CI = (-0.22, -0.03)], as well as urine aMT6s levels [1 study, migraine n = 146, HC n = 74, MD = -11.90 µg/nocturnal (12 hours) urine collection, 95%CI = (-19.23, -4.57)] in adult migraine patients compared to HC [1 study involving children did not reveal any difference regarding nocturnal urine aMT6s, n = 18 per group, MD = -6.00 µg/nocturnal (12 hours) urine collection, 95%CI = (-21.19, 9.19)]. Regarding the treatment-prevention of migraine, 7 RCTs and 9 non-randomized studies were retrieved. Data synthesis was not feasible for the comparison of melatonin and placebo due to the existing clinical and methodological heterogeneity of the 5 relevant RCTs. Overall, melatonin was more efficacious and equally safe with placebo in the prevention of migraine in adults (3 of 4 RCTs provided superior efficacy results for melatonin, 1 RCT revealed no difference regarding Headache Frequency -HF-), while there are limited data for children (1 RCT revealed no difference against placebo regarding HF). Additionally, no difference was revealed between melatonin and amitriptyline (1 RCT), sodium valproate (1 RCT) or propranolol (1 non-randomized study) with respect to their efficacy in adults with migraine, while melatonin was more effective than pizotifen (1 RCT). In children with migraine, amitriptyline is more efficacious regarding most assessed parameters (2 studies, n = 85 per group, HF: RE MD = 4.03, 95%CI = (2.64, 5.42), Headache Duration: RE MD = 0.72, 95%CI = (0.41, 1.03), Headache Severity: FE MD = 1.57, 95%CI = (1.13, 2.00), Response to Treatment: FE MD = 0.33, 95%CI = (0.16, 0.69), Headache Induced Disability Severity: RE MD = 6.07, 95%CI = (-11.87, 24.01 ), Analgesic Consumption - assessed in 1 study, n = 40 per group - MD = 1.11, 95%CI = (-0.10, 2.32)), although melatonin presents a superior safety profile than amitriptyline both in adults and in children. CONCLUSIONS: Melatonin may be of potential benefit in the treatment-prevention of migraine in adults, but complementary evidence from high-quality RCTs is required.

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BACKGROUND: Nurses and midwives make up almost 50% of the global healthcare shift working workforce. Shift work interferes with sleep and causes fatigue with adverse effects for nurses' and midwives' health, as well as on patient safety and care. Where other safety-critical sectors have developed Fatigue Risk Management Systems, healthcare is behind the curve; with published literature only focussing on the evaluation of discreet sleep-related/fatigue-management interventions. Little is known, however, about which interventions have been evaluated for nurses and midwives. Our review is a critical first step to building the evidence-base for healthcare organisations seeking to address this important operational issue. OBJECTIVES: We address two questions: (1) what sleep-related/fatigue-management interventions have been assessed in nurses and midwives and what is their evidence-base? and (2) what measures are used by researchers to assess intervention effectiveness? DESIGN AND DATA SOURCES: The following databases were searched in November, 2018 with no limit on publication dates: MEDLINE, PsychINFO and CINAHL. REVIEW METHODS: We included: (1) studies conducted in adult samples of nurses and/or midwives that had evaluated a sleep-related/fatigue-management intervention; and (2) studies that reported intervention effects on fatigue, sleep, or performance at work, and on measures of attention or cognitive performance (as they relate to the impact of shift working on patient safety/care). RESULTS: The search identified 798 potentially relevant articles, out of which 32 met our inclusion criteria. There were 8619 participants across the included studies and all were nurses (88.6% female). We did not find any studies conducted in midwives nor any studies conducted in the UK, with most studies conducted in the US, Italy and Taiwan. There was heterogeneity both in terms of the interventions evaluated and the measures used to assess effectiveness. Napping could be beneficial but there was wide variation regarding nap duration and timing, and we need to understand more about barriers to implementation. Longer shifts, shift patterns including nights, and inadequate recovery time between shifts (quick returns) were associated with poorer sleep, increased sleepiness and increased levels of fatigue. Light exposure and/or light attenuation interventions showed promise but the literature was dominated by small, potentially unrepresentative samples. CONCLUSIONS: The literature related to sleep-related/fatigue-management interventions for nurses and midwives is fragmented and lacks cohesion. Further empirical work is warranted with a view to developing comprehensive Fatigue Risk Management Systems to protect against fatigue in nurses, midwives, and other shift working healthcare staff.

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Hepatocellular carcinoma (HCC) is the sixth most frequent neoplasm and the second leading cause of cancer-related deaths worldwide. Nonalcoholic fatty liver disease (NAFLD), a common disorder in obese people, has been identified as an important risk factor for HCC. Following the increasing prevalence of obesity, it is expected that the contribution of NAFLD to HCC's incidence worldwide will grow. Recently, a number of studies have been published, which help us better understand cellular and molecular mechanisms of how NAFLD promotes hepatocarcinogensis. Inflammatory cytokines, ER stress and circadian dysregulation, which mediate hepatocyte injury and NAFLD progression, have been identified to promote malignant transformation of hepatocytes. Besides these 'intrinsic' effects, lipid dysregulation dramatically affects the liver local microenvironment. The reshaped immune environment has also been found to contribute to the NAFLD-mediated hepatocarcinogenesis. This review explores recent findings of both 'intrinsic' effects on hepatocytes and the role of the local environment in NAFLD-promoted HCC development.

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Disturbances in circadian rhythms have been suggested as a possible cause of bipolar disorder (BD). Included in this study were 31 mood episodes of 26 BD patients, and 18 controls. Circadian rhythms of BD were evaluated at admission, at 2-week intervals during hospitalization, and at discharge. All participants wore wrist actigraphs during the studies. Saliva and buccal cells were obtained at 8:00, 11:00, 15:00, 19:00, and 23:00 for two consecutive days. Collected saliva and buccal cells were used for analysis of the cortisol and gene circadian rhythm, respectively. Circadian rhythms had different phases during acute mood episodes of BD compared to recovered states. In 23 acute manic episodes, circadian phases were ~7hour advanced (equivalent to ~17hour delayed). Phases of 21 out of these 23 cases returned to normal by ~7hour delay along with treatment, but two out of 23 cases returned to normal by ~17hour advance. In three cases of mixed manic episodes, the phases were ~6-7hour delayed. For five cases of depressive episodes, circadian rhythms phases were ~4-5hour delayed. After treatment, circadian phases resembled those of healthy controls. Circadian misalignment due to circadian rhythm phase shifts might be a pathophysiological mechanism of BD.

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