Reconstitution of Monocyte Subsets and PD-L1 Expression but Not T Cell PD-1 Expression in Obstructive Sleep Apnea Patients upon PAP Therapy

Obstructive sleep apnea (OSA) is characterized by nocturnal breathing intermissions resulting in oxidative stress and eventually, a low-grade systemic inflammation. The study aimed to investigate the impact of positive airway pressure (PAP) therapy on the inflammatory milieu as measured by monocyte and T cell phenotypic alterations. Participants were assessed for their OSA severity before PAP therapy and about six months later, including patient-reported outcome and therapy usage by telemetry readout. The distributions of the CD14/CD16-characterized monocyte subsets as well as the CD4/CD8-characterized effector T cell subsets with regard to their PD-1 and PD-L1 expression were analyzed by flow cytometry from blood samples. Data of 25 patients revealed a significant reconstitution of the monocyte subset distribution and a decrease in PD-L1 expression on pan-monocytes and CD8⁺ T cells without an association to initial AHI and overweight. The PD-1 expression was still increased on T cell subsets, especially on CD4⁺ TH17/22 cells. We conclude that PAP therapy might have a rapid effect on the monocyte phenotype and overall PD-L1 expression levels. However, T cell immune alterations especially on TH17/22 cells persist longer, indicating an ongoing disturbance of the adaptive immune system.     

Discovery of Highly Potent Dual Orexin Receptor Antagonists via a Scaffold‐Hopping Approach

Starting from suvorexant (trade name Belsomra), we successfully identified interesting templates leading to potent dual orexin receptor antagonists (DORAs) via a scaffold‐hopping approach. Structure–activity relationship optimization allowed us not only to improve the antagonistic potency on both orexin 1 and orexin 2 receptors (Ox1 and Ox2, respectively), but also to increase metabolic stability in human liver microsomes (HLM), decrease time‐dependent inhibition of cytochrome P450 (CYP) 3A4, and decrease P‐glycoprotein (Pgp)‐mediated efflux. Compound 80 c [{(1S,6R)‐3‐(6,7‐difluoroquinoxalin‐2‐yl)‐3,8‐diazabicyclo[4.2.0]octan‐8‐yl}(4‐methyl‐[1,1′‐biphenyl]‐2‐yl)methanone] is a potent and selective DORA that inhibits the stimulating effects of orexin peptides OXA and OXB at both Ox1 and Ox2. In calcium‐release assays, 80 c was found to exhibit an insurmountable antagonistic profile at both Ox1 and Ox2, while displaying a sleep‐promoting effect in rat and dog models, similar to that of the benchmark compound suvorexant.     

Fatigue, sleep loss, and confidence in judgment.

Sixty-four adults participated in a study examining the accuracy of metacognitive judgments during 28 hr of sleep deprivation (SD) and continuous cognitive work. Three tasks were studied (perceptual comparison, general knowledge, and mental addition), collectively spanning a range of cognitive abilities and levels of susceptibility to SD. Subjective and objective measures of sleepiness confirmed the expected patterns of increasing fatigue with SD. Participants displayed differing levels of metacognitive abilities across tasks, but traditional indices of the confidence-accuracy relation (i.e., calibration, resolution, over- and underconfidence), as well as the accuracy of pre- and posttask estimates of performance, remained stable over the SD period. The findings suggest that people can accurately assess their own cognitive performance when deprived of 1 night of sleep and that this ability need not be based on subjective estimates of sleepiness. The implications and limitations of the study are discussed and directions for future research are proposed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interhemispheric asymmetry of human sleep EEG in response to selective slow-wave sleep deprivation.

Recent evidence suggests that the human sleep electroencephalogram (EEG) shows regional differences over both the sagittal and coronal planes. In the present study, in a group of 10 right-handers, the authors investigated the presence of hemispheric asymmetries in the homeostatic regulation of human sleep EEG power during and after selective slow-wave sleep (SWS) deprivation. The SWS deprivation was slightly more effective over the right hemisphere, but the left hemisphere showed a markedly larger increase of EEG power in the 1.00-24.75 Hz range during recovery-night non-REM sleep, and a larger increase of EEG power during both deprivation-night and recovery-night REM sleep. These results support the greater need for sleep recuperative processes of the left hemisphere, suggesting that local sleep regulation processes may also act during REM sleep. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

慢波和异相睡眠生理功能与人类工效的探讨

文章通过回顾近年来对睡眠成份ＳＷＳ和ＲＥＭＳ的研究资料，认为ＳＷＳ和ＲＥＭＳ节律在人的一生睡眠中的不同时期除了本身的生理需要外，还可通过现在已知的外界人控因素加以改变，这些因素对ＳＷＳ和ＲＥＭＳ节律的调节具有预防、治疗疾病和提高人类工效的作用。文章着重讨论和介绍了身心健康和不健康的个体如何增加或减少ＳＷＳ和ＲＥＭＳ的多种简单、实用的方法。     

Individual differences in mental activity at sleep onset.

Reports of sleep-onset and nocturnal (EEG Stage 1, REM period) mentation, CPIs, and thematic fantasy responses were collected from 32 young-adult Ss. In confirmation of recent findings by Foulkes and Vogel, dreamlike mental activity was found to occur with fairly substantial frequency at sleep onset, albeit with wide individual differences. Patterning of personality correlates with hypnagogic and nocturnal dream recall suggests that the former varies directly with waking ego strength and adaptive flexibility, while the latter varies directly with indications of waking maladaptive symptomatology. A psychodynamic interpretation of these results is offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Doubling the rate of signal presentation in a vigilance task during sleep deprivation.

An experiment was conducted to test the effect of doubling the amount of work required of Ss after loss of sleep. Ss were required to detect defined sequences of 3 digits ("signals") within an apparently random series. Digits were presented continuously for 30 min. either at 1 per sec. (slow) or 2 per sec. (fast). The slow condition contained 20 signals; the fast condition 40. Slow and fast groups were tested on 3 successive days of a 60-hr. vigil and 2 similar groups under control conditions. The results showed that loss of sleep affects performance under fast less than under slow. These and other results suggested that stimulation reduces the effect of sleepiness on performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Individual differences in dream recall.

Ss who typically fail to remember dreams at home (nonreporters) and Ss who frequently remember dreams (reporters) slept in the laboratory for 4 nights each. Gradual or abrupt awakenings were made at each EEG Stage-I REM (dream) period. Although nonreporters and reporters did not differ in REM-period frequency or EEG patterns during sleep, nonreporters did report dreaming less frequently following REM-period awakenings. Ss showed self-consistency in frequency of dream reporting and in type of failure to report. Some nonreporters typically failed to remember any content; others typically said they were awake and thinking. Comparisons among reporters and sub-groups of nonreporters for eye-movement frequency, arousal threshold, and dreamlike-report content indicate that it may be useful to distinguish different kinds of nonreporters. (17 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning during sleep?

Studies on the sleep-learning phenomenon are criticized in terms of weaknesses in experimental design, statistics and methodology employed, and criteria of sleep. While it is highly speculative that the studies reviewed show that sleep-learning is possible, "The conditions under which the results were found tend more to support the contention that some learning takes place in a special kind of waking state wherein Ss apparently do not remember later on if they had been awake. This may be of great practical importance from the standpoint of economy in study time, but it cannot be construed as sleep-learning." 25 references. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

百合水提物对对氯苯丙氨酸失眠模型大鼠睡眠改善作用研究

目的 研究不同剂量的百合水提取物对对氯苯丙氨酸(PCPA)失眠模型大鼠睡眠作用的影响。方法 大鼠腹腔注射PCPA混悬液制备大鼠失眠模型。将造模成功大鼠随机分为模型对照组、百合水提物组-低、百合水提物组-中、百合水提物组-高,另设空白对照组。百合水提物组-低 (100 mg/kg.d)、百合水提物组-中(200 mg/kg.d)、百合水提物组-高(300 mg/kg.d)大鼠连续 7 d 给予相应浓度药液,模型对照组和空白对照组连续 7 d 给予生理盐水灌胃。给药期间,观察大鼠一般状态;给药结束后,观察大鼠体质量变化、睡眠潜伏期、总睡眠时间,同时评价不同脑组织中五羟色胺、5-羟基吲哚乙酸、多巴胺含量的变化。结果 百合水提物各剂量组的大鼠在给药期间的一般状态均优于模型组,体质量增加情况也与正常对照组无显著差异;百合水提物中、高剂量组的睡眠潜伏期与模型组相比显著缩短(P＜0.05),百合水提物各剂量组的睡眠时间与模型组相比显著延长(P＜0.05);与模型对照组比较,各给药组大鼠不同脑组织中的5-HT含量显著升高(P < 0.05,P < 0.01),百合水提物中、高剂量组大鼠不同脑组织中的5-HIAA 含量显著升高(P < 0.05,P < 0.01),同时上述２个给药组大鼠的下丘脑、中缝核中的DA含量显著降低(P < 0.05),海马中仅百合水提物高剂量组的DA含量与对照组相比显著降低(P < 0.05)。结论 百合水提物具有改善PCPA失眠模型大鼠睡眠情况的作用。