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Can the Brain's Thermostatic Mechanism Generate Sleep-Wake and NREM-REM Sleep Cycles? A Nested Doll Model of Sleep-Regulating Processes. 大脑恒温机制能否产生睡眠-觉醒和 NREM-REM 睡眠周期?睡眠调节过程的嵌套玩偶模型。
IF 3.1 Q3 CLINICAL NEUROLOGY Pub Date : 2024-02-19 DOI: 10.3390/clockssleep6010008
Arcady A Putilov

Evidence is gradually accumulating in support of the hypothesis that a process of thermostatic brain cooling and warming underlies sleep cycles, i.e., the alternations between non-rapid-eye-movement and rapid-eye-movement sleep throughout the sleep phase of the sleep-wake cycle. A mathematical thermostat model predicts an exponential shape of fluctuations in temperature above and below the desired temperature setpoint. If the thermostatic process underlies sleep cycles, can this model explain the mechanisms governing the sleep cyclicities in humans? The proposed nested doll model incorporates Process s generating sleep cycles into Process S generating sleep-wake cycles of the two-process model of sleep-wake regulation. Process s produces ultradian fluctuations around the setpoint, while Process S turns this setpoint up and down in accord with the durations of the preceding wake phase and the following sleep phase of the sleep-wake cycle, respectively. Predictions of the model were obtained in an in silico study and confirmed by simulations of oscillations of spectral electroencephalographic indexes of sleep regulation obtained from night sleep and multiple napping attempts. Only simple-inverse exponential and exponential-functions from the thermostatic model were used for predictions and simulations of rather complex and varying shapes of sleep cycles during an all-night sleep episode. To further test the proposed model, experiments on mammal species with monophasic sleep are required. If supported, this model can provide a valuable framework for understanding the involvement of sleep-wake regulatory processes in the mechanism of thermostatic brain cooling/warming.

越来越多的证据支持这样一种假设,即大脑恒温的冷却和升温过程是睡眠周期的基础,即在睡眠-觉醒周期的整个睡眠阶段,非快速眼动睡眠和快速眼动睡眠之间的交替。恒温器的数学模型预测,温度在所需温度设定点上下的波动呈指数形状。如果恒温过程是睡眠周期的基础,那么这个模型能否解释人类的睡眠周期机制呢?所提出的嵌套娃娃模型将产生睡眠周期的过程 s 纳入了睡眠-觉醒双过程调节模型中产生睡眠-觉醒周期的过程 S 中。过程 s 围绕设定点产生超昼夜波动,而过程 S 则分别根据睡眠-觉醒周期中前一个觉醒阶段和后一个睡眠阶段的持续时间上下调整该设定点。该模型的预测是在一项硅学研究中获得的,并通过模拟夜间睡眠和多次小睡尝试中获得的睡眠调节频谱脑电图指标的振荡得到了证实。只有恒温模型中的简单反指数函数和指数函数被用于预测和模拟整夜睡眠过程中复杂多变的睡眠周期。为了进一步验证所提出的模型,需要在单相睡眠的哺乳动物物种上进行实验。如果得到支持,该模型将为理解恒温大脑降温/升温机制中睡眠-觉醒调节过程的参与提供一个有价值的框架。
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引用次数: 0
Bright Light Therapy for Major Depressive Disorder in Adolescent Outpatients: A Preliminary Study. 亮光疗法治疗青少年门诊患者的重度抑郁症:初步研究。
IF 3.1 Q3 CLINICAL NEUROLOGY Pub Date : 2024-01-30 DOI: 10.3390/clockssleep6010005
Rachel Ballard, John T Parkhurst, Lisa K Gadek, Kelsey M Julian, Amy Yang, Lauren N Pasetes, Namni Goel, Dorothy K Sit

Background: Bright light therapy (BLT) has not been well-studied in adolescents with major depressive disorder, particularly in outpatient settings.

Methods: We conducted an 8-week clinical trial of BLT in adolescents recruited from a primary care practice with moderate to severe major depression. Acceptability and feasibility were defined by daily use of the light box and integration into daily routines. To assess treatment effects, we utilized the Short Mood and Feelings Questionnaire (SMFQ) and actigraphic sleep variables.

Results: Of the nine enrolled adolescents, the rate of daily use of the light therapy box was 100% at week 2, 78% at week 4 (n = 7), and 67% at weeks 6 and 8 (n = 6). Participants were better able to integrate midday BLT compared to morning BLT into their day-to-day routines. Mean depression scores improved during the 2-week placebo lead-in (dim red light-DRL) and continued to show significant improvement through 6 weeks of BLT. Sleep efficiency increased significantly (p = 0.046), and sleep onset latency showed a trend toward a significant decrease (p = 0.075) in the BLT phase compared to the DRL phase.

Conclusion: Bright light treatment that was self-administered at home was feasible, acceptable, and effective for adolescent outpatients with depression. Findings support the development of larger, well-powered, controlled clinical trials of BLT in coordination with primary care.

背景:亮光疗法(BLT)在患有重度抑郁症的青少年中尚未得到充分研究,尤其是在门诊环境中:我们对从初级保健诊所招募的患有中度至重度重度抑郁症的青少年进行了为期 8 周的亮光疗法临床试验。可接受性和可行性由灯箱的日常使用和与日常生活的结合来定义。为了评估治疗效果,我们使用了简短情绪和感觉问卷(SMFQ)以及行为记录睡眠变量:结果:在 9 名参加治疗的青少年中,第 2 周每天使用光疗箱的比例为 100%,第 4 周为 78%(7 人),第 6 周和第 8 周为 67%(6 人)。与早上使用光疗箱相比,参与者能更好地将中午光疗箱融入日常作息中。在为期 2 周的安慰剂引导期(昏暗红光-DRL)中,平均抑郁评分有所改善,在 BLT 6 周后仍有显著改善。睡眠效率明显提高(p = 0.046),与DRL阶段相比,BLT阶段的睡眠开始潜伏期呈明显下降趋势(p = 0.075):结论:对门诊青少年抑郁症患者来说,在家中自行进行的强光治疗是可行的、可接受的、有效的。研究结果支持在基层医疗机构的配合下,开展更大规模的、有充分证据支持的BLT临床对照试验。
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引用次数: 0
Integrative Lighting Aimed at Patients with Psychiatric and Neurological Disorders. 针对精神和神经疾病患者的综合照明。
IF 3.1 Q3 CLINICAL NEUROLOGY Pub Date : 2023-12-15 DOI: 10.3390/clockssleep5040052
Xinxi Zeng, Thierry Silvio Claude Soreze, Martin Ballegaard, Paul Michael Petersen

The purpose of this paper is to investigate the impact of circadian lighting-induced melatonin suppression on patients with psychiatric and neurological disorders in hospital wards by using an ad-hoc metrology framework and the subsequent metrics formalized by the CIE in 2018. A measurement scheme was conducted in hospital ward rooms in the Department of Neurology, Zealand University Hospital, at Roskilde in Denmark, to evaluate the photometric and colorimetric characteristics of the lighting system, as well as its influence on the circadian rhythm of the occupants. The measurement scheme included point measurements and data logging, using a spectrophotometer mounted on a tripod with adjustable height to assess the newly installed circadian lighting system. The measured spectra were uploaded to the Luox platform to calculate illuminance, CCT, MEDI, etc., in accordance with the CIE S026 standard. Furthermore, the MLIT based on MEDI data logging results was calculated. In addition to CIE S026, we have investigated the usefulness of melatonin suppression models for the assessment of circadian performance regarding measured light. From the results, the lighting conditions in the patient room for both minimal and abundant daylight access were evaluated and compared; we found that access to daylight is essential for both illumination and circadian entrainment. It can be concluded that the measurement scheme, together with the use of the Luox platform and Canva template, is suitable for the accurate and satisfactory measurement of integrative lighting that aligns with CIE requirements and recommendations.

本文旨在通过使用一个临时计量框架和随后由 CIE 于 2018 年正式确定的度量标准,研究昼夜节律照明引起的褪黑激素抑制对医院病房中精神和神经紊乱患者的影响。测量计划在丹麦罗斯基勒的西兰大学医院神经科病房进行,以评估照明系统的光度和色度特性及其对居住者昼夜节律的影响。测量方案包括点测量和数据记录,使用安装在可调节高度的三脚架上的分光光度计来评估新安装的昼夜节律照明系统。测量到的光谱被上传到 Luox 平台,以便根据 CIE S026 标准计算照度、CCT、MEDI 等。此外,还根据 MEDI 数据记录结果计算了 MLIT。除 CIE S026 标准外,我们还研究了褪黑激素抑制模型在评估测量光照的昼夜节律性能方面的实用性。从结果来看,我们评估并比较了病房中日照最少和日照充足的照明条件;我们发现,日照对照明和昼夜节律调节都至关重要。可以得出的结论是,该测量方案以及对 Luox 平台和 Canva 模板的使用,适用于对符合 CIE 要求和建议的综合照明进行准确和令人满意的测量。
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引用次数: 0
Methods for REM Sleep Density Analysis: A Scoping Review. 快速动眼期睡眠密度分析方法:范围综述
IF 3.1 Q3 CLINICAL NEUROLOGY Pub Date : 2023-12-14 DOI: 10.3390/clockssleep5040051
Tamires Tiemi Kishi, Monica Levy Andersen, Ygor Matos Luciano, Viviane Akemi Kakazu, Sergio Tufik, Gabriel Natan Pires

Rapid eye movements (REM) sleep density is the parameter proposed to explain the variability in the amount of eye movements during REM sleep. Alterations in REM sleep density have been proposed as a screening criterion for individuals with depression and other mental health conditions, but its accuracy has not been properly evaluated. The lack of consensus and the variability of the methods used to score it reduces the external validity of the results, hindering an adequate analysis of its diagnostic accuracy and clinical applicability. This scoping review aimed to identify and quantify the methods used to score REM sleep density, describing their main characteristics. A literature search was conducted in PubMed, Scopus, PsycInfo, and Web of Science. Only studies with objective measures for REM sleep density analysis in individuals with depression were considered eligible. The final sample comprised 57 articles, covering 64 analyses of REM sleep density. The relative frequency methods were the predominant measurement parameter for analyzing REM sleep density across studies. The most frequently adopted REM estimation unit was the number of REM events followed by mini-epochs containing REM. The most common unit of measurement were frequency/time measures. The results demonstrate that there is no consistency in the methods used to calculate REM sleep density in the literature, and a high percentage of studies do not describe their methods in sufficient detail. The most used method was the number of REM episodes per minute of REM sleep, but its use is neither unanimous nor consensual. The methodological inconsistencies and omissions among studies limit the replicability, comparability, and clinical applicability of REM sleep density. Future guidelines should discuss and include a specific methodology for the scoring of REM sleep density, so it can be consensually implemented in clinical services and research.

快速眼动(REM)睡眠密度是用来解释快速眼动睡眠期间眼球运动量变化的参数。有人建议将快速眼动睡眠密度的变化作为抑郁症和其他精神疾病患者的筛查标准,但其准确性尚未得到适当评估。由于缺乏共识以及评分方法的多样性,降低了结果的外部有效性,阻碍了对其诊断准确性和临床适用性的充分分析。本范围综述旨在确定和量化用于评分快速动眼期睡眠密度的方法,并描述其主要特征。我们在 PubMed、Scopus、PsycInfo 和 Web of Science 上进行了文献检索。只有对抑郁症患者的快速动眼期睡眠密度进行客观分析的研究才符合条件。最终样本包括 57 篇文章,涉及 64 项快速动眼期睡眠密度分析。在所有研究中,相对频率法是分析快速眼动睡眠密度的主要测量参数。最常采用的快速动眼期估计单位是快速动眼期事件的数量,其次是包含快速动眼期的小节段。最常见的测量单位是频率/时间测量。研究结果表明,文献中用于计算快速眼动睡眠密度的方法并不一致,有很大比例的研究没有对其方法进行足够详细的描述。使用最多的方法是每分钟快速动眼期睡眠的快速动眼期发作次数,但这种方法的使用既不一致,也没有达成共识。研究方法的不一致和遗漏限制了快速动眼期睡眠密度的可复制性、可比性和临床适用性。未来的指南应讨论并纳入快速动眼期睡眠密度评分的具体方法,以便在临床服务和研究中得到一致认可。
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引用次数: 0
Microbiota Composition and Probiotics Supplementations on Sleep Quality-A Systematic Review and Meta-Analysis. 微生物群组成和益生菌补充剂对睡眠质量的影响--系统回顾和元分析。
IF 3.1 Q3 CLINICAL NEUROLOGY Pub Date : 2023-12-13 DOI: 10.3390/clockssleep5040050
Daniele Santi, Valentina Debbi, Francesco Costantino, Giorgia Spaggiari, Manuela Simoni, Carla Greco, Livio Casarini

The gut microbiota (GM) plays a crucial role in human health. The bidirectional interaction between GM and the central nervous system may occur via the microbiota-gut-brain axis, possibly regulating the sleep/wake cycle. Recent reports highlight associations between intestinal dysbiosis and sleep disorders, suggesting that probiotics could ameliorate this condition. However, data are poor and inconsistent. The aim of this quantitative metanalytic study is to assess the GM composition in sleep disturbances and evaluate probiotics' effectiveness for managing sleep disorders. A systematic review was carried out until July 2022 in online databases, limiting the literature research to human studies and English language articles. No significant GM diversity between patients with sleep disturbances versus healthy controls was found, revealed by α-diversity, while β-diversity is missing due to lack of proper reporting. However, probiotics supplementation significantly reduced the self-assessed parameter of sleep quality and disturbances Pittsburgh Sleep Quality Index (PSQI) score compared with the placebo. No difference in the Epworth Sleepiness Scale (ESS) score was found. While available data suggest that GM diversity is not related to sleep disturbances, probiotics administration strongly improves sleep quality as a subjective perception. However, heterogeneity of data reporting in the scientific literature should be considered as a limitation.

肠道微生物群(GM)对人类健康起着至关重要的作用。肠道微生物群与中枢神经系统之间的双向互动可能是通过微生物群-肠道-大脑轴发生的,可能调节睡眠/觉醒周期。最近的报道强调了肠道菌群失调与睡眠障碍之间的联系,表明益生菌可以改善这种状况。然而,这方面的数据很少,而且不一致。这项定量元分析研究旨在评估睡眠障碍中的转基因成分,并评估益生菌对控制睡眠障碍的效果。截至 2022 年 7 月,我们在在线数据库中进行了系统性回顾,文献研究仅限于人类研究和英文文章。结果发现,睡眠障碍患者与健康对照组之间没有明显的基因组多样性差异,α-多样性显示了这一点,而β-多样性则由于缺乏适当的报告而缺失。然而,与安慰剂相比,补充益生菌能显著降低自我评估的睡眠质量参数和干扰匹兹堡睡眠质量指数(PSQI)得分。在埃普沃思嗜睡量表(ESS)得分方面没有发现差异。虽然现有数据表明转基因多样性与睡眠障碍无关,但作为一种主观感受,服用益生菌能显著改善睡眠质量。然而,科学文献中数据报告的异质性应被视为一个局限。
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引用次数: 0
Diagnostic Accuracy of a Portable Electromyography and Electrocardiography Device to Measure Sleep Bruxism in a Sleep Apnea Population: A Comparative Study. 便携式肌电图和心电图仪在睡眠呼吸暂停人群中测量睡眠磨牙的诊断准确性:一项比较研究。
IF 3.1 Q3 CLINICAL NEUROLOGY Pub Date : 2023-11-20 DOI: 10.3390/clockssleep5040047
Rosana Cid-Verdejo, Adelaida A Domínguez Gordillo, Eleuterio A Sánchez-Romero, Ignacio Ardizone García, Francisco J Martínez Orozco

Background: The gold standard for diagnosing sleep bruxism (SB) and obstructive sleep apnea (OSA) is polysomnography (PSG). However, a final hypermotor muscle activity often occurs after apnea episodes, which can confuse the diagnosis of SB when using portable electromyography (EMG) devices. This study aimed to compare the number of SB episodes obtained from PSG with manual analysis by a sleep expert, and from a manual and automatic analysis of an EMG and electrocardiography (EKG) device, in a population with suspected OSA.

Methods: Twenty-two subjects underwent a polysomnographic study with simultaneous recording with the EMG-EKG device. SB episodes and SB index measured with both tools and analyzed manually and automatically were compared. Masticatory muscle activity was scored according to published criteria. Patients were segmented by severity of OSA (mild, moderate, severe) following the American Academy of Sleep Medicine (AASM) criteria. ANOVA and the Bland-Altman plot were used to quantify the agreement between both methods. The concordance was calculated through the intraclass correlation coefficient (ICC).

Results: On average, the total events of SB per night in the PSG study were (8.41 ± 0.85), lower than the one obtained with EMG-EKG manual (14.64 ± 0.76) and automatic (22.68 ± 16.02) analysis. The mean number of SB episodes decreases from the non-OSA group to the OSA group with both PSG (5.93 ± 8.64) and EMG-EKG analyses (automatic = 22.47 ± 18.07, manual = 13.93 ± 11.08). However, this decrease was minor in proportion compared to the automatic EMG-EKG analysis mode (from 23.14 to 22.47). The ICC based on the number of SB episodes in the segmented sample by severity degree of OSA along the three tools shows a moderate correlation in the non-OSA (0.61) and mild OSA (0.53) groups. However, it is poorly correlated in the moderate (0.24) and severe (0.23) OSA groups: the EMG-EKG automatic analysis measures 14.27 units more than PSG. The results of the manual EMG-EKG analysis improved this correlation but are not good enough.

Conclusions: The results obtained in the PSG manual analysis and those obtained by the EMG-EKG device with automatic and manual analysis for the diagnosis of SB are acceptable but only in patients without OSA or with mild OSA. In patients with moderate or severe OSA, SB diagnosis with portable electromyography devices can be confused due to apneas, and further study is needed to investigate this.

背景:诊断睡眠磨牙症(SB)和阻塞性睡眠呼吸暂停(OSA)的金标准是多导睡眠图(PSG)。然而,最终的过度运动肌肉活动通常发生在呼吸暂停发作后,这在使用便携式肌电图(EMG)设备时可能会混淆SB的诊断。本研究旨在比较疑似OSA患者的PSG与睡眠专家手工分析的SB发作次数,以及手工和自动分析的EMG和心电图(EKG)设备。方法:对22名受试者进行多导睡眠图研究,同时用肌电心电图仪记录。用这两种工具分别测量SB发作数和SB指数,并进行人工和自动比较分析。根据公布的标准对咀嚼肌活动进行评分。按照美国睡眠医学会(AASM)的标准,将患者按照OSA的严重程度(轻度、中度、重度)进行分类。方差分析和Bland-Altman图用于量化两种方法之间的一致性。通过类内相关系数(ICC)计算一致性。结果:PSG组平均每晚SB总事件数为(8.41±0.85)次,低于手动(14.64±0.76)和自动(22.68±16.02)分析。经PSG(5.93±8.64)和EMG-EKG(自动= 22.47±18.07,手动= 13.93±11.08)分析,平均SB发作次数从非OSA组减少到OSA组。然而,与自动肌电-心电图分析模式相比,这种下降比例很小(从23.14降至22.47)。根据OSA严重程度分段样本中SB发作次数的ICC沿三个工具显示,非OSA组(0.61)和轻度OSA组(0.53)之间存在中度相关性。然而,在中度(0.24)和重度(0.23)OSA组中相关性较差:肌电心电图自动分析比PSG多14.27个单位。手工肌电心电图分析的结果改善了这种相关性,但还不够好。结论:PSG手工分析和肌电心电图自动和手工分析诊断SB的结果均可接受,但仅适用于无OSA或轻度OSA患者。在中度或重度OSA患者中,便携式肌电仪的SB诊断可能因呼吸暂停而混淆,需要进一步研究。
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引用次数: 0
The Wave Model of Sleep Dynamics and an Invariant Relationship between NonREM and REM Sleep. 睡眠动力学的波模型及非快速眼动和快速眼动睡眠的不变关系。
IF 3.1 Q3 CLINICAL NEUROLOGY Pub Date : 2023-11-17 DOI: 10.3390/clockssleep5040046
Vasili Kharchenko, Irina V Zhdanova

Explaining the complex structure and dynamics of sleep, which consist of alternating and physiologically distinct nonREM and REM sleep episodes, has posed a significant challenge. In this study, we demonstrate that a single-wave model concept captures the distinctly different overnight dynamics of the four primary sleep measures-the duration and intensity of nonREM and REM sleep episodes-with high quantitative precision for both regular and extended sleep. The model also accurately predicts how these polysomnographic measures respond to sleep deprivation or abundance. Furthermore, the model passes the ultimate test, as its prediction leads to a novel experimental finding-an invariant relationship between the duration of nonREM episodes and the intensity of REM episodes, the product of which remains constant over consecutive sleep cycles. These results suggest a functional unity between nonREM and REM sleep, establishing a comprehensive and quantitative framework for understanding normal sleep and sleep disorders.

解释睡眠的复杂结构和动力学,包括交替和生理上不同的非快速眼动和快速眼动睡眠,已经提出了重大挑战。在这项研究中,我们证明了单波模型概念捕捉了四种主要睡眠测量的明显不同的夜间动态——非快速眼动睡眠和快速眼动睡眠的持续时间和强度——对常规睡眠和延长睡眠都有很高的定量精度。该模型还准确地预测了这些多导睡眠图测量对睡眠剥夺或充足的反应。此外,该模型通过了最终测试,因为它的预测导致了一个新的实验发现——非快速眼动发作的持续时间和快速眼动发作的强度之间存在不变的关系,其结果在连续的睡眠周期中保持不变。这些结果表明非快速眼动睡眠和快速眼动睡眠在功能上是统一的,为理解正常睡眠和睡眠障碍建立了全面和定量的框架。
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引用次数: 0
Associations between Rest–Activity Rhythms and Liver Function Tests: The US National Health and Nutrition Examination Survey, 2011–2014 休息-活动节律和肝功能测试之间的关系:美国国家健康和营养检查调查,2011-2014
Q3 CLINICAL NEUROLOGY Pub Date : 2023-11-02 DOI: 10.3390/clockssleep5040045
Chris Ho Ching Yeung, Cici Bauer, Qian Xiao
Liver functions are regulated by the circadian rhythm; however, whether a weakened circadian rhythm is associated with impaired liver function is unclear. This study aims to investigate the association of characteristics of rest–activity rhythms with abnormal levels of biomarkers of liver function. Data were obtained from the National Health and Nutrition Examination Survey 2011–2014. Seven rest–activity rhythm parameters were derived from 24 h actigraphy data using the extended cosine model and non-parametric methods. Multiple logistic regression and multiple linear regression models were used to assess the associations between rest–activity rhythm parameters and alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transaminase (GGT), albumin and bilirubin. Weakened overall rhythmicity characterized by a lower F statistic was associated with higher odds of abnormally elevated ALP (ORQ1vs.Q5: 2.16; 95% CI 1.19, 3.90) and GGT (ORQ1vs.Q5: 2.04; 95% CI 1.30, 3.20) and abnormally lowered albumin (ORQ1vs.Q5: 5.15; 95% CI 2.14, 12.38). Similar results were found for a lower amplitude, amplitude:mesor ratio, interdaily stability and intradaily variability. Results were robust to the adjustment of confounders and cannot be fully explained by individual rest–activity behaviors, including sleep and physical activity. Weakened rest–activity rhythms were associated with worse liver function as measured by multiple biomarkers, supporting a potential role of circadian rhythms in liver health.
肝功能受昼夜节律调节;然而,昼夜节律减弱是否与肝功能受损有关尚不清楚。本研究旨在探讨休息-活动节律特征与肝功能生物标志物异常水平的关系。数据来源于2011-2014年全国健康与营养检查调查。采用扩展余弦模型和非参数方法,从24 h活动记录仪数据中得到7个休息-活动节律参数。采用多元logistic回归和多元线性回归模型评估静息-活动节律参数与丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、γ -谷氨酰转氨酶(GGT)、白蛋白和胆红素的关系。以较低F统计值为特征的整体节律性减弱与ALP (ORQ1vs)异常升高的几率较高相关。Q5: 2.16;95% CI 1.19, 3.90)和GGT (ORQ1vs。Q5: 2.04;95% CI 1.30, 3.20)和异常降低的白蛋白(ORQ1vs)。Q5: 5.15;95% ci 2.14, 12.38)。在较低的振幅、振幅:中介率、日间稳定性和日内变异性方面也发现了类似的结果。结果对混杂因素的调整是稳健的,不能完全用个人的休息-活动行为来解释,包括睡眠和身体活动。通过多种生物标志物测量,休息-活动节律减弱与肝功能恶化相关,支持昼夜节律在肝脏健康中的潜在作用。
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引用次数: 0
Seasonal Variation in the Responsiveness of the Melanopsin System to Evening Light: Why We Should Report Season When Collecting Data in Human Sleep and Circadian Studies 黑视素系统对夜间光线反应的季节变化:为什么我们在收集人类睡眠和昼夜节律研究数据时应该报告季节
Q3 CLINICAL NEUROLOGY Pub Date : 2023-11-01 DOI: 10.3390/clockssleep5040044
Isabel Schöllhorn, Oliver Stefani, Christine Blume, Christian Cajochen
It is well known that variations in light exposure during the day affect light sensitivity in the evening. More daylight reduces sensitivity, and less daylight increases it. On average days, we spend less time outdoors in winter and receive far less light than in summer. Therefore, it could be relevant when collecting research data on the non-image forming (NIF) effects of light on circadian rhythms and sleep. In fact, studies conducted only in winter may result in more pronounced NIF effects than in summer. Here, we systematically collected information on the extent to which studies on the NIF effects of evening light include information on season and/or light history. We found that more studies were conducted in winter than in summer and that reporting when a study was conducted or measuring individual light history is not currently a standard in sleep and circadian research. In addition, we sought to evaluate seasonal variations in a previously published dataset of 72 participants investigating circadian and sleep effects of evening light exposure in a laboratory protocol where daytime light history was not controlled. In this study, we selectively modulated melanopic irradiance at four different light levels (<90 lx). Here, we aimed to retrospectively evaluate seasonal variations in the responsiveness of the melanopsin system by combining all data sets in an exploratory manner. Our analyses suggest that light sensitivity is indeed reduced in summer compared to winter. Thus, to increase the reproducibility of NIF effects on sleep and circadian measures, we recommend an assessment of the light history and encourage standardization of reporting guidelines on the seasonal distribution of measurements.
众所周知,白天光照的变化会影响晚上的光敏度。更多的日光会降低灵敏度,而更少的日光会增加灵敏度。平均而言,冬天我们在户外的时间比夏天少,接受到的光线也比夏天少得多。因此,在收集光对昼夜节律和睡眠的非图像形成(NIF)影响的研究数据时,它可能是相关的。事实上,仅在冬季进行的研究可能会导致比夏季更明显的NIF效应。在这里,我们系统地收集了关于夜间光照对NIF影响的研究在多大程度上包括季节和/或光照历史的信息。我们发现,在冬季进行的研究比在夏季进行的研究要多,而在睡眠和昼夜节律研究中,报告何时进行研究或测量个人光照史并不是目前的标准。此外,我们试图在先前发表的72名参与者的数据集中评估季节性变化,这些参与者在实验室协议中调查了夜间光照对昼夜节律和睡眠的影响,其中白天的光照历史没有控制。在本研究中,我们在四种不同的光照水平(<90 lx)下选择性地调制了褪黑辐照度。在这里,我们旨在通过探索性的方式结合所有数据集,回顾性地评估黑视素系统响应性的季节性变化。我们的分析表明,与冬季相比,夏季的光敏感性确实降低了。因此,为了提高NIF对睡眠和昼夜节律测量影响的可重复性,我们建议对光照史进行评估,并鼓励标准化测量数据季节性分布的报告指南。
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引用次数: 0
The Antihypertensive Guanabenz Exacerbates Integrated Stress Response and Disrupts the Brain Circadian Clock 降压药Guanabenz加重综合应激反应并扰乱大脑生物钟
Q3 CLINICAL NEUROLOGY Pub Date : 2023-10-31 DOI: 10.3390/clockssleep5040043
Hao Lin, Muhammad Naveed, Aidan Hansen, Tracy G. Anthony, Ruifeng Cao
The circadian clock regulates a variety of biological processes that are normally synchronized with the solar day. Disruption of circadian rhythms is associated with health problems. Understanding the signaling mechanisms that couple cell physiology and metabolism to circadian timekeeping will help to develop novel therapeutic strategies. The integrated stress response (ISR) is activated by the cellular stressors to maintain physiological homeostasis by orchestrating mRNA translation. Aberrant ISR has been found in a number of neurological diseases that exhibit disrupted circadian rhythms and sleep. Recent work has started to uncover a critical role for the ISR in regulating the physiology of the circadian clock. Guanabenz (2,6-dichlorobenzylidene aminoguanidine acetate) is an orally bioavailable α2-adrenergic receptor agonist that has been used as an antihypertensive for decades. Recent studies demonstrated that guanabenz can regulate the ISR. Here, we assessed the effects of guanabenz on cellular and behavioral circadian rhythms using a multidisciplinary approach. We found that guanabenz can induce the ISR by increasing eIF2α phosphorylation in cultured fibroblasts as well as in the mouse brain. The hyperphosphorylation of eIF2α by guanabenz is associated with the shortened circadian period in cells and animals and the disruption of behavioral circadian rhythms in mice. Guanabenz administration disrupted circadian oscillations of the clock protein Per1 and Per2 in the mouse suprachiasmatic nucleus, the master pacemaker. These results uncover a significant yet previously unidentified role of guanabenz in regulating circadian rhythms and indicate that exacerbated ISR activation can impair the functions of the brain’s circadian clock by disrupting clock gene expression.
生物钟调节着各种生物过程,这些过程通常与太阳日同步。昼夜节律紊乱与健康问题有关。了解将细胞生理和代谢与昼夜节律相结合的信号机制将有助于开发新的治疗策略。综合应激反应(integrated stress response, ISR)由细胞应激源激活,通过调控mRNA的翻译来维持生理稳态。在许多表现出昼夜节律和睡眠中断的神经系统疾病中发现了异常的ISR。最近的研究已经开始揭示ISR在调节生理时钟方面的关键作用。Guanabenz(2,6-二氯苄胺胍醋酸酯)是一种口服α2-肾上腺素能受体激动剂,几十年来一直被用作降压药。近年来的研究表明,胍苯胺可以调节ISR。在这里,我们使用多学科方法评估了胍那苯对细胞和行为昼夜节律的影响。我们发现,胍苯苯可以通过增加培养成纤维细胞和小鼠大脑中eIF2α的磷酸化来诱导ISR。guanabenz对eIF2α的过度磷酸化与细胞和动物的昼夜节律缩短以及小鼠行为昼夜节律的破坏有关。Guanabenz给药破坏了小鼠视交叉上核(主起搏器)中时钟蛋白Per1和Per2的昼夜节律振荡。这些结果揭示了guanabenz在调节昼夜节律中的重要作用,并且表明ISR激活加剧可以通过破坏生物钟基因表达来损害大脑生物钟的功能。
{"title":"The Antihypertensive Guanabenz Exacerbates Integrated Stress Response and Disrupts the Brain Circadian Clock","authors":"Hao Lin, Muhammad Naveed, Aidan Hansen, Tracy G. Anthony, Ruifeng Cao","doi":"10.3390/clockssleep5040043","DOIUrl":"https://doi.org/10.3390/clockssleep5040043","url":null,"abstract":"The circadian clock regulates a variety of biological processes that are normally synchronized with the solar day. Disruption of circadian rhythms is associated with health problems. Understanding the signaling mechanisms that couple cell physiology and metabolism to circadian timekeeping will help to develop novel therapeutic strategies. The integrated stress response (ISR) is activated by the cellular stressors to maintain physiological homeostasis by orchestrating mRNA translation. Aberrant ISR has been found in a number of neurological diseases that exhibit disrupted circadian rhythms and sleep. Recent work has started to uncover a critical role for the ISR in regulating the physiology of the circadian clock. Guanabenz (2,6-dichlorobenzylidene aminoguanidine acetate) is an orally bioavailable α2-adrenergic receptor agonist that has been used as an antihypertensive for decades. Recent studies demonstrated that guanabenz can regulate the ISR. Here, we assessed the effects of guanabenz on cellular and behavioral circadian rhythms using a multidisciplinary approach. We found that guanabenz can induce the ISR by increasing eIF2α phosphorylation in cultured fibroblasts as well as in the mouse brain. The hyperphosphorylation of eIF2α by guanabenz is associated with the shortened circadian period in cells and animals and the disruption of behavioral circadian rhythms in mice. Guanabenz administration disrupted circadian oscillations of the clock protein Per1 and Per2 in the mouse suprachiasmatic nucleus, the master pacemaker. These results uncover a significant yet previously unidentified role of guanabenz in regulating circadian rhythms and indicate that exacerbated ISR activation can impair the functions of the brain’s circadian clock by disrupting clock gene expression.","PeriodicalId":33568,"journal":{"name":"Clocks & Sleep","volume":"70 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135809498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Clocks & Sleep
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