Euphausia pacifica emulsified oil powder improves sleep quality in partially sleep-restricted healthy volunteers.

Although it is known that adequate sleep is crucial for maintaining a healthy lifestyle, approximately 30% of the general population has experienced insomnia. Thus, a better understanding of the relationship between food components and sleep quality is needed. North Pacific krill, Euphausia pacifica, is rich in marine n-3 polyunsaturated fatty acids in phospholipid form as well as 8R-hydroxy-eicosapentanoic acid. Here, emulsified oil powder derived from this krill was used in a trial involving 64 participants to assess its potential to enhance sleep quality. Consumption of the powdered emulsified oil was found to reduce drowsiness upon waking and enhance fatigue recovery, and for participants aged 40 and above, an improvement in sleep cycle was observed. In conclusion, consumption of krill emulsified oil powder was effective in enhancing sleep quality for individuals with partial sleep restrictions.

Anxiolytic-like activity of Aloysia virgatavar. platyphylla leaves extract in mice / Actividad ansiolítica del extracto de hojas de Aloysia virgatavar. platyphylla en ratones

Background: Medicinal plants are part of traditional medicine and should be considered a therapeutic alternative for mental diseases. Several plants belonging to the Verbenaceae family have proved useful in treating general anxiety disorders, the most prevalent psychiatric disorders. Objective: This research aimed to verify the extract's safety, the effect on general behavior, and the effect on sleeping time, as well as to evaluate the anxiolytic-like effect of the methanol extract of Aloysia virgata var. platyphylla (Avp), in mice. Methodology: The toxicity test was done according to the OECD guide (mice groups n=5), and general behavior was observed during the assay. Sleeping time was assessed using the pentobarbital-induced hypnosis method (n=8). Male Swiss albino mice (n=6) were treated with 50 to 400 mg/kg of Avp extract and diazepam as a control. The anxiolytic-like effect was tested through the hole board and elevated plus-maze test. Results: The Avp extract has no side effects in tested doses, and no central nervous system depressant activity was noted. A. virgatavar. platyphyllaincreased exploration (number and time) in the hole board. In the elevated plus-maze, increased number and time into open arms were evidenced compared to the control group. Conclusion: With all these results, we concluded that the Avp extract is safe and has a potential anxiolytic-like activity in the animal model used

Antecedentes: Las plantas medicinales forman parte de la medicina tradicional y deben ser consideradas una alternativa terapéutica para las enfermedades mentales. Varias plantas pertenecientes a la familia Verbenaceae han demostrado su utilidad en el tratamiento de los trastornos de ansiedad, uno de los trastornos psiquiátricos más prevalentes. Objetivo: Esta investigación tuvo como objetivo verificar la seguridad del extracto, el efecto sobre el comportamiento general y el efecto sobre el tiempo de sueño, así como evaluar el efecto tipo ansiolítico del extracto metanólico de Aloysia virgata var. platyphylla(Avp), en ratones. Metodología: La prueba de toxicidad se realizó de acuerdo con la guía de la OCDE (grupos de ratones n=5), y se observó el comportamiento general durante el ensayo. El tiempo de sueño se evaluó mediante el método de hipnosis inducida por pentobarbital (n=8). Se trataron ratones albinos suizos macho (n=6) con 50 a 400 mg/kg de extracto de Avp y diazepam como control. El efecto ansiolítico se probó a través de la placa perforada y prueba del laberinto en cruz elevado. Resultados: El extracto de Avp no tiene efectos secundarios en las dosis probadas y no se observó actividad depresora del sistema nervioso central. A. virgata var. platyphylla aumentó la exploración (número y tiempo) en el tablero de agujeros. En el laberinto en cruz elevado, se evidenció un mayor número y tiempo en los brazos abiertos en comparación con el grupo de control. Conclusión: Con todos estos resultados, concluimos que el extracto de Avp es seguro y tiene una potencial actividad ansiolítica en el modelo animal utilizado

Sleep-promoting activity of lotus (Nelumbo nucifera) rhizome water extract via GABAA receptors.

CONTEXT: The sleep-promoting activity of Nelumbo nucifera Gaertn. (Nymphaeaceae) alkaloids in leaves or seeds are well known. However, the sleep-promoting activity of the lotus rhizome (LE), which is used mainly as food, has not yet been evaluated. OBJECTIVE: We investigated the sleep-promoting activity of LE water extract. MATERIALS AND METHODS: Institute of Cancer Research (ICR) mice (n = 8) were subject to a pentobarbital-induced sleep test to assess changes in sleep latency and duration following the administration of LE (80-150 mg/kg). In addition, electroencephalography analysis was performed to determine the sleep quality after LE treatment as well as the sleep recovery effect of LE using a caffeine-induced insomnia SD rat model. Real-time PCR and western blot analysis were performed to investigate the expression of neurotransmitter receptors, and the GABAA receptor antagonists were used for receptor binding analysis. RESULTS: An oral administration of 150 mg/kg LE significantly increased sleep duration by 24% compared to the control. Furthermore, LE increased nonrapid eye movement (NREM) sleep by increasing theta and delta powers. In the insomnia model, LE increased sleep time by increasing NREM sleep. Moreover, treatment with picrotoxin and flumazenil decreased the sleep time by 33% and 23%, respectively, indicating an involvement of the GABAA receptor in the sleep-enhancing activity of LE. The expression of GABAA receptors and the concentration of GABA in the brain were increased by LE. DISCUSSION AND CONCLUSIONS: The results suggest that the sleep-promoting activity of LE was via the GABAA receptor. Collectively, these data show that LE may promote sleep.

Effect of Hibiscus syriacus Linnaeus extract and its active constituent, saponarin, in animal models of stress-induced sleep disturbances and pentobarbital-induced sleep.

Treatment of sleep disorders promotes the long-term use of commercially available sleep inducers that have several adverse effects, including addiction, systemic fatigue, weakness, loss of concentration, headache, and digestive problems. Therefore, we aimed to limit these adverse effects by investigating a natural product, the extract of the Hibiscus syriacus Linnaeus flower (HSF), as an alternative treatment. In the electric footshock model, we measured anxiety and assessed the degree of sleep improvement after administering HSF extract. In the restraint model, we studied the sleep rate using PiezoSleep, a noninvasive assessment system. In the pentobarbital model, we measured sleep improvement and changes in sleep-related factors. Our first model confirmed the desirable effects of HSF extract and its active constituent, saponarin, on anxiolysis and Wake times. HSF extract also increased REM sleep time. Furthermore, HSF extract and saponarin increased the expression of cortical GABAA receptor α1 (GABAAR α1) and c-Fos in the ventrolateral preoptic nucleus (VLPO). In the second model, HSF extract and saponarin restored the sleep rate and the sleep bout duration. In the third model, HSF extract and saponarin increased sleep maintenance time. Moreover, HSF extract and saponarin increased cortical cholecystokinin (CCK) mRNA levels and the expression of VLPO c-Fos. HSF extract also increased GABAAR α1 mRNA level. Our results suggest that HSF extract and saponarin are effective in maintaining sleep and may be used as a novel treatment for sleep disorder. Eventually, we hope to introduce HSF and saponarin as a clinical treatment for sleep disorders in humans.

Involvement of the adenosine A1 receptor in the hypnotic effect of rosmarinic acid.

Insomnia, the most common sleep disorder, is characterized by a longer sleep latency, greater sleep fragmentation, and consequent excessive daytime fatigue. Due to the various side effects of prescribed hypnotics, demand for new drugs is still high. Recent studies have suggested the adenosine receptor (AR) as a potential therapeutic target for insomnia, however, clinically useful hypnotics targeting AR are not yet available. In the present study, we evaluated the hypnotic effect of rosmarinic acid, a phenolic compound widely found in medicinal plants, through pentobarbital-induced sleep test, electroencephalography/electromyography (EEG/EMG), and immunohistochemistry in mice. The underlying mechanisms were assessed by pharmacological approach using 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and SCH5826, antagonists for A1R and A2AR, respectively. Receptor-binding assay and functional agonism were also performed. Our study provides a new evidence that rosmarinic acid has a direct binding activity (Ki = 14.21 ± 0.3 µM) and agonistic activity for A1R. We also found that rosmarinic acid significantly decreased sleep fragmentation and onset latency to NREM sleep, and these effects were abolished by DPCPX. The results from c-Fos immunostaining showed that rosmarinic acid decreased the neuronal activity in wake-promoting brain regions, such as the basal forebrain and the lateral hypothalamus, while increasing the neuronal activity in the ventrolateral preoptic nucleus, a sleep-promoting region; all these effects were significantly inhibited by DPCPX. Taken together, this study suggests that rosmarinic acid possesses novel activity as an A1R agonist and thereby exerts a hypnotic effect, and thus it may serve as a potential therapeutic agent for insomnia through targeting A1R.

A randomized double-blind placebo-controlled trial of the effectiveness of melatonin on neurocognition and sleep in survivors of childhood cancer.

BACKGROUND: Adult survivors of childhood cancer are at risk of developing sleep and neurocognitive problems, yet few efficacious interventions exist targeting these prevalent late effects. Melatonin has known sleep-promoting effects; however, it has not been well studied among childhood cancer survivors. METHOD: Survivors (n = 580; mean age = 33.5 years; 26 years post-diagnosis) from the St. Jude Lifetime Cohort were randomized (1:1) to a six-month double-blind placebo-controlled trial of 3 mg time-release melatonin within three strata (stratum 1: neurocognitive impairment only; stratum 2: neurocognitive and sleep impairment; stratum 3: sleep impairment only). Neurocognitive performance was assessed at baseline and post-intervention using standardized measures. Sleep was assessed via self-report and actigraphy. Independent sample t tests compared mean change scores from baseline to six months. Post-hoc analyses compared the prevalence of clinically significant treatment responders among melatonin and placebo conditions within and across strata. RESULTS: Intent-to-treat analyses revealed no statistically significant differences in neurocognitive performance or sleep from baseline to post-intervention. However, among survivors with neurocognitive impairment only, a larger proportion randomized to melatonin versus placebo demonstrated a treatment response for visuomotor speed (63% vs 41%, P = 0.02) and nonverbal reasoning (46% vs 28%, P = 0.04). Among survivors with sleep impairment only, a larger proportion treated with melatonin demonstrated a treatment response for shifting attention (44% vs 28%, P = 0.05), short-term memory (39% vs 19%, P = 0.01), and actigraphy-assessed sleep duration (47% vs 29%, P = 0.05). CONCLUSION: Melatonin was not associated with improved neurocognitive performance or sleep in our intent-to-treat analyses; however, a subset of survivors demonstrated a clinically significant treatment response.

Application of Chaihu-Guizhi-Longgu-Muli decoction combined with Liuwei Dihuang Pills in the treatment of menopausal insomnia and its effect on sleep quality.

To explore the application of Chaihu-Guizhi-Longgu-Muli decoction (CGLM) combined with Liuwei Dihuang Pills in the treatment of menopausal insomnia and its effect on sleep quality. The data of 120 menopausal insomnia patients admitted to our hospital from February 2019 to February 2020 were retrospectively analyzed and they were equally divided into the experimental group (n=60) and the control group (n=60) according to the order of admission. All patients were treated with Liuwei Dihuang Pills, and the experimental group was additionally given CGLM. The Pittsburgh Sleep Quality Index (PSQI), estrogen level, negative emotion score, quality of life score, serum ß-endorphin (ß-EP) level, serotonin level (5-HT) and treatment effective rate were compared between the two groups of patients. After treatment, the experimental group obtained markedly lower PSQI scores and negative emotion scores than the control group (P<0.001). The estrogen levels, ß-EP levels and 5-HT levels of the experimental group after treatment were significantly better than those of the control group (P<0.001). Higher quality of life scores and treatment effective rates were observed in the experimental group after treatment than the control group (P<0.001). CGLM combined with Liuwei Dihuang Pills can regulate the serum hormone levels of patients with menopausal insomnia, reduce negative emotions and improve sleep quality and quality of life, which merits clinical promotion.

A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening.

Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, we developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening. We comprehensively tested this formulation in two separate studies. First, we established the in vivo caffeine release profile in 10 young men. Subsequently, we investigated in placebo-controlled, double-blind, cross-over fashion the formulation's ability to improve sleep inertia in 22 sleep-restricted volunteers. Following oral administration of 160 mg caffeine at 22:30, we kept volunteers awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening at 07:00. Immediately upon awakening, we quantified subjective state, psychomotor vigilance, cognitive performance, and followed the evolution of the cortisol awakening response. We also recorded standard polysomnography during nocturnal sleep and a 1-h nap opportunity at 08:00. Compared to placebo, the engineered caffeine formula accelerated the reaction time on the psychomotor vigilance task, increased positive and reduced negative affect scores, improved sleep inertia ratings, prolonged the cortisol awakening response, and delayed nap sleep latency one hour after scheduled awakening. Based on these findings, we conclude that this novel, pulsatile-release caffeine formulation facilitates the sleep-to-wake transition in sleep-restricted healthy adults. We propose that individuals suffering from disabling sleep inertia may benefit from this innovative approach.Trials registration: NCT04975360.

Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials.

OBJECTIVE: To determine the benefits and harms of medical cannabis and cannabinoids for chronic pain. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, AMED, PsycInfo, CENTRAL, CINAHL, PubMed, Web of Science, Cannabis-Med, Epistemonikos, and trial registries up to January 2021. STUDY SELECTION: Randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1 month follow-up. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently assessed risk of bias and extracted data. We performed random-effects models meta-analyses and used GRADE to assess the certainty of evidence. RESULTS: A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer related pain (n=4). Length of follow-up ranged from 1 to 5.5 months. Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of -0.50 cm (95% CI -0.75 to -0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of -0.35 cm (-0.55 to -0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect). CONCLUSIONS: Moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo. The accompanying BMJ Rapid Recommendation provides contextualised guidance based on this body of evidence. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/3pwn2.

Chronic Toxoplasma gondii infection and sleep-wake alterations in mice.

AIM: Toxoplasma gondii (Tg) is an intracellular parasite infecting more than a third of the human population. Yet, the impact of Tg infection on sleep, a highly sensitive index of brain functions, remains unknown. We designed an experimental mouse model of chronic Tg infection to assess the effects on sleep-wake states. METHODS: Mice were infected using cysts of the type II Prugniaud strain. We performed chronic sleep-wake recordings and monitoring as well as EEG power spectral density analysis in order to assess the quantitative and qualitative changes of sleep-wake states. Pharmacological approach was combined to evaluate the direct impact of the infection and inflammation caused by Tg. RESULTS: Infected mouse exhibited chronic sleep-wake alterations over months, characterized by a marked increase (>20%) in time spent awake and in cortical EEG θ power density of all sleep-wake states. Meanwhile, slow-wave sleep decreased significantly. These effects were alleviated by an anti-inflammatory treatment using corticosteroid dexamethasone. CONCLUSION: We demonstrated for the first time the direct consequences of Tg infection on sleep-wake states. The persistently increased wakefulness and reduced sleep fit with the parasite's strategy to enhance dissemination through host predation and are of significance in understanding the neurodegenerative and neuropsychiatric disorders reported in infected patients.

1,25(OH)2 D3 attenuates sleep disturbance in mouse models of Lewis lung cancer, in silico and in vivo.

Many clinical studies have reported that patients diagnosed with cancer will suffer from sleep disturbance during their clinical process, especially among lung cancer patients, and this effect will not easily subside. 1,25-dihydroxy-vitamin-D3 [1,25(OH)2 D3 ], the activated form of vitamin D, can participate in neuronal differentiation and prevent damage to the nervous system. However, little is known about the potential therapeutic effects of cancer-related psychiatric symptoms. In light of this, we hypothesized that a low circulating level of vitamin D was related to sleep quality in the presence of a tumor, 1,25(OH)2 D3 may be an effective way to ameliorate sleep disturbance and neurochemical alterations along with the cancer progress. Male C57BL/6 mice were implanted with intracranial transmitters to monitor electroencephalogram and were subcutaneously inoculated with Lewis lung cancer cells. The results demonstrated that on Days 19-20, tumor-bearing mice displayed fragmented sleep, shortened wake phase, prolonged sleep in the non-rapid eye movement phase, and the levels of vitamin D-associated genes in the brain had changed a lot compared to control mice. Importantly, 1,25(OH)2 D3 treatment really effectively saved the sleep quality of tumor-bearing mice. We further explored and confirmed that 1,25(OH)2 D3 repressed tumor-induced neuroinflammation (IL-1ß, TNF-α, IL-6, IL-10, IFN-γ, and IL-2), enhanced neurotrophic factors (brain-derived neurotrophic factor [BDNF], glialcellline-derived neurotrophic factor) and 5-HT system in the hippocampus, hypothalamus or cortex. A molecular docking approah manifested the ability of 1,25(OH)2 D3 to affect the activity of tryptophan hydroxylase 2 and BDNF. Together, our results suggested that 1,25(OH)2 D3 treatment may attenuate sleep disturbance in Lewis lung cancer-bearing mice, and become a promising strategy for treating cancer symptom clusters to ameliorate the quality of life of patients with cancer.

Importancia del buen dormir en nuestros pacientes / Importance of good sleep in our patients

El sueño es una necesidad biológica. Regula las funciones inmunitarias. Las funciones inmunológicas dependen de los ritmos circadianos y del sueño regular. Según estudios previos a la pandemia, la corta duración del sueño o privación de sueño, en la semana cercana a la vacunación, se asocia con respuestas más bajas de anticuerpos. La privación de sueño da como resultado una función inmunológica más deficiente (es decir, actividad reducida de las células natural killer, producción de IL-2 suprimida) así como un aumento de los niveles circulantes de marcadores inflamatorios (IL-6, TNF-α [factor de necrosis tumoral] y proteína C reactiva). Los médicos deben ser conscientes de que muchas enfermedades que mencionamos en esta resumida actualización son comórbidas con alteraciones del sueño, y es importante, por ello, enseñar a los pacientes a mejorar su comportamiento con respecto al sueño y fomentar la educación sobre higiene del sueño. Destacamos que, en el interrogatorio de cualquier especialidad médica, deben incorporarse preguntas sobre el "dormir", dado que el sueño de buena calidad es fundamental en la prevención y el tratamiento de diversas enfermedades. (AU)

Sleep is a biological necessity. Regulates immune functions. Immune functions depend on circadian rhythms and regular sleep. According to studies prior to the pandemic, short duration of sleep or sleep deprivation, in the week leading up to vaccination, is associated with lower antibody responses to vaccination. Sleep deprivation results in poorer immune function (i.e., reduced natural killer cell activity, suppressed IL-2 production) as well as increased circulating levels of inflammatory markers (IL-6, factor of tumor necrosis, C-reactive protein). Clinicians should be aware that many illnesses, which we mention in this brief update, are comorbid with sleep disturbances and it is therefore important to teach patients to improve their sleep behavior and should encourage sleep hygiene education . We emphasize that in the questioning of any medical specialty, questions about "sleep" should be incorporated, given that good quality sleep is essential in the prevention and treatment of various diseases. (AU)

Interaction between cocaine use and sleep behavior: A comprehensive review of cocaine's disrupting influence on sleep behavior and sleep disruptions influence on reward seeking.

Dopamine, orexin (hypocretin), and adenosine systems have dual roles in reward and sleep/arousal suggesting possible mechanisms whereby drugs of abuse may influence both reward and sleep/arousal. While considerable variability exists across studies, drugs of abuse such as cocaine induce an acute sleep loss followed by an immediate recovery pattern that is consistent with a normal response to loss of sleep. Under more chronic cocaine exposure conditions, an abnormal recovery pattern is expressed that includes a retention of sleep disturbance under withdrawal and into abstinence conditions. Conversely, experimentally induced sleep disturbance can increase cocaine seeking. Thus, complementary, sleep-related therapeutic approaches may deserve further consideration along with development of non-human models to better characterize sleep disturbance-reward seeking interactions across drug experience.

Characterization of pharmaco-EEG fingerprint and sleep-wake profiles of Lavandula angustifolia Mill. essential oil inhalation and diazepam administration in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Lavandula angustifolia Mill. Essential oil (Lavender EO) has a long history of medicinal use and is particularly claimed to possess anxiolytic and sedative properties. Lavender EO aromatherapy has been used to reduce distress and improve insomnia naturally. Increasing evidence appeared to show similarities between the effects of lavender EO and the anxiolytic drugs, benzodiazepines. However, its effects on sleep-wake and electrical brain patterns in comparison to that of the standard anxiolytic, diazepam, remained to be explored. AIM OF THE STUDY: The aim of this work was to investigate electroencephalography (EEG) profiles and sleep-pattern elicited by lavender EO inhalation compared to that of diazepam, a standard anxiolytic drug in in vivo rat model. MATERIALS AND METHODS: Adult male Wistar rats were anesthetized for electrode implantation on the frontal and parietal skulls. EEG signals were recorded for 180 min following intraperitoneal injection of diazepam (10 mg/kg) or during continuous inhalation of lavender EO (200 µL) or distilled water (control). Fast Fourier transform was used for the analyses of EEG power spectra and sleep-wake parameters. RESULTS: During a 30-60 min period, diazepam and lavender EO significantly increased frontal powers of 0.78-45.31 and 7.03-18.36 Hz, respectively. Both treatments also increased parietal powers with lower magnitudes of significant change. Significant increases in some frequency ranges remained until a 60-90 min period. Sleep-wake analyses also revealed that diazepam significantly reduced time spent in wake, increased time spent in non-rapid eye movement (NREM), increased episode duration of NREM, decreased numbers of wake episode and decreased rapid eye movement (REM) sleep latency. On the other hand, lavender EO only significantly decreased wake episodes and latency to REM sleep. Lavender EO inhalation reduced numbers of wake episode but maintain normal time spent in wake, NREM and REM sleeps. CONCLUSIONS: These findings might suggest beneficial and distinct anxiolytic-like effects of lavender EO for sleep enhancing purposes.

Effect of Dexmedetomidine on Postoperative Sleep Quality: A Systematic Review.

In this article, we conduct a systematic review of the literature to explore the specific role of dexmedetomidine (DEX) on postoperative sleep and its associated mechanisms at present. The electronic database Embase, MEDLINE/PubMed, the Cochrane Library, Web of Science, and Google Scholar were searched. The restriction terms included "dexmedetomidine", "sleep" and "surgery". The inclusion criteria were as following: 1) patients 18 years old or older; 2) DEX used in the perioperative period not just for critically ill patients in the intensive care unit (ICU); 3) prospective or retrospective studies. The review articles, conference abstracts, and animal studies were excluded. Out of the 22 articles which met the above criteria, 20 of them were randomized controlled studies and 2 of them were retrospective cohort studies. Infusion of DEX including during the surgery and after surgery at a low or high dose was shown to improve subjective and objective sleep quality, although 2 studies showed there is no evidence that the use of DEX improves sleep quality and 1 showed less sleep efficiency and shorter total sleep time in the DEX group. Other postoperative outcomes evaluated postoperative nausea and vomiting, pain, postoperative delirium bradycardia and hypotension. Outcomes of our systematic review showed that DEX has advantages in improving patients' postoperative sleep quality. Combined with the use of general anesthetic, DEX provides a reliable choice for procedural sedation.

Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.

The accumulation of adenosine is strongly correlated with the need for sleep and the detection of sleep pressure is antagonised by caffeine. Caffeine also affects the circadian timing system directly and independently of sleep physiology, but how caffeine mediates these effects upon the circadian clock is unclear. Here we identify an adenosine-based regulatory mechanism that allows sleep and circadian processes to interact for the optimisation of sleep/wake timing in mice. Adenosine encodes sleep history and this signal modulates circadian entrainment by light. Pharmacological and genetic approaches demonstrate that adenosine acts upon the circadian clockwork via adenosine A1/A2A receptor signalling through the activation of the Ca2+ -ERK-AP-1 and CREB/CRTC1-CRE pathways to regulate the clock genes Per1 and Per2. We show that these signalling pathways converge upon and inhibit the same pathways activated by light. Thus, circadian entrainment by light is systematically modulated on a daily basis by sleep history. These findings contribute to our understanding of how adenosine integrates signalling from both light and sleep to regulate circadian timing in mice.

Pharmacologically Induced Ventilatory Depression in the Postoperative Patient: A Sleep-Wake State-Dependent Perspective.

Pharmacologically induced ventilatory depression (PIVD) is a common postoperative complication with a spectrum of severity ranging from mild hypoventilation to severe ventilatory depression, potentially leading to anoxic brain injury and death. Recent studies, using continuous monitoring technologies, have revealed alarming rates of previously undetected severe episodes of postoperative ventilatory depression, rendering the recognition of such episodes by the standard intermittent assessment practice, quite problematic. This imprecise description of the epidemiologic landscape of PIVD has thus stymied efforts to understand better its pathophysiology and quantify relevant risk factors for this postoperative complication. The residual effects of various perianesthetic agents on ventilatory control, as well as the multiple interactions of these drugs with patient-related factors and phenotypes, make postoperative recovery of ventilation after surgery and anesthesia a highly complex physiological event. The sleep-wake, state-dependent variation in the control of ventilation seems to play a central role in the mechanisms potentially enhancing the risk for PIVD. Herein, we discuss emerging evidence regarding the epidemiology, risk factors, and potential mechanisms of PIVD.

Effects of preoperative oral single-dose and double-dose carbohydrates on insulin resistance in patients undergoing gastrectomy:a prospective randomized controlled trial.

BACKGROUND & AIMS: Preoperative oral carbohydrates are strongly recommended for routine use before various elective procedures. The regimen mainly includes preoperative oral single-dose carbohydrate (2-3 h before surgery) and preoperative oral double-dose carbohydrates (10 h before surgery and 2-3 h before surgery). The choice between the two options is still controversial. METHODS: A total of 139 patients with gastric cancer who underwent radical gastrectomy were recruited from a hospital in Sichuan Province, China. The patients were randomly assigned to a single-dose group (n = 70) or a double-dose group (n = 69). Insulin resistance indicators, subjective comfort indicators, inflammatory mediators, immunological indicators, postoperative recovery indexes, and complications were compared between the two groups. RESULTS: There were no differences in insulin resistance indicators (fasting plasma glucose, fasting insulin, and homeostasis model assessment indexes), inflammatory mediators (C-reactive protein, interleukin-6, and tumor necrosis factor-α), immunological indicators (CD3+, CD4+, CD8+, and CD4+/CD8+) between the single-dose group and double-dose group (all P > 0.05) at preoperative day 1, preoperative 3 h, and postoperative day 1. There were no differences in subjective comfort indicators (thirst, hunger, anxiety, nausea, fatigue, and weakness) between the two groups (all P > 0.05) at preoperative day 1, preoperative 3 h, preoperative 1 h, and postoperative day 1. The postoperative recovery indexes and complications (exhaust time, liquid intake time, postoperative hospital stay, complication incidence, unplanned readmission rate, and unplanned reoperation rate 30 days after operation) did not significantly differ between the two groups (all P > 0.05). The number of preoperative nighttime urinations in the double-dose group was higher than that in the single-dose group (88.3% VS 48.5%, P < 0.001), and the number of hours of preoperative sleep in the double-dose group was lower than that in the single-dose group (4.56 ± 0.68 VS 5.71 ± 0.57, P < 0.001). CONCLUSION: Oral carbohydrates administered the night before surgery did not enhance the effects of oral carbohydrates administered 2-3 h before surgery on insulin resistance, subjective comfort, inflammation, and immunity and might affect the patients' night rest. In making a decision between oral carbohydrate regimes, evening carbohydrates could be omitted. TRIAL REGISTRATION: ChiCTR, ChiCTR1900020608. Registered January 10, 2019, http://www.chictr.org.cn: ChiCTR1900020608.

Enzymolysis peptides from Mauremys mutica plastron improve the disorder of neurotransmitter system and facilitate sleep-promoting in the PCPA-induced insomnia mice.

ETHNOPHARMACOLOGY RELEVANCY: For many centuries, Mauremys mutica is highly valued as a food homologous Chinese herbal medicine. It has been considered useful to sedate, nourish brain and promote sleep. However, the animal experimental evidence of its sleep-promoting activity is missing in literature. AIM OF THE STUDY: In this study, PCPA-induced insomnia model was used to explore the sleep-promoting mechanism of enzymolysis peptides from PMM, and its main composition and chemical structure were analyzed. MATERIALS AND METHODS: Experiments were performed using PCPA-induced insomnia model, all animals were intraperitoneally injected with PCPA (350 mg/kg·d) for two days. The sleep-promoting effect evaluated using measuring content of 5-HT, GABA, DA, IL-1, BDNF and expression of 5-HT1A receptor and GABAA receptor α1-subunit in mice brain. Primary structure of peptides was identified by HPLC-ESI-QqTOF-MS/MS. RESULTS: Compared with the model group, the content of 5-HT, GABA, IL-1, BDNF in mice brain of PMM peptide groups was increased to varying degrees, the content of DA was decreased, and the gene transcription and protein expression of 5-HT1A receptor and GABAA receptor α1-subunit were almost all returned to normal levels. In addition, the primary structures of most abundant nine typical peptides in PMM peptides were identified. CONCLUSIONS: The results showed that PMM peptides could improve the disorder of neurotransmitter system, restore compensatory over-expression 5-HT1A receptor and GABAA receptor α1-subunit, and have a good sleep-promoting effect. The specific amino acid composition, sequence and glycosylation modification of PMM peptides may be the key reason for their activity, which lays a foundation for the subsequent development of sleep-promoting peptide products.