Eurycoma longifolia (Tongkat Ali) enhances wakefulness during active periods but facilitates sleep during resting periods in C57BL/6 mice.

The effects of the Eurycoma longifolia (also known as Tongkat Ali [TA]) on sleep and wakefulness was evaluated in C57BL/6 mice. While TA has been used as an aphrodisiac in males, it exhibits various pharmacological effects. The most notable effect observed with TA was wake-enhancement during the second half of the active period, accompanied by significant elevations in core body temperature (CBT). In contrast, sleep was enhanced during the resting period (i.e., increase in rapid eye movement [REM] sleep and delta electroencephalography [EEG] power in non-REM sleep) with significant declines in CBT. The transition of TA's effects between resting and active periods was rapid. The results of the experiments in constant darkness indicate that TA prolongs the circadian tau and that this transition is governed by circadian clock mechanisms rather than light exposure. TA did not demonstrate efficacy in aiding sleep in an acute stress-induced insomnia model; thus, TA may be more suitable as a wake-enhancing agent for daytime sleepiness, as sleep propensity tends to accumulate towards the end of active period. Since TA amplifies the rest-activity pattern, prolongs circadian tau and increases REM sleep, thereby reversing some common symptoms seen in elderly subjects, it may also hold promise as a rejuvenating medicine.

Influences of sleep and lifestyle factors on the risk for covid-19 infections, from internet survey of 10,000 Japanese business workers.

We conducted an internet survey to assess sociodemographic variables, lifestyle factors, sleep problems, and comorbidities for sleep apnea syndrome (SAS) in COVID-19 and influenza (FLU) infections. Data from 10,323 workers (50.0% male) were analyzed. COVID-19 was diagnosed in 144 subjects (COVID-19+), and 8,693 were classified as not suspected to be infected (COVID-19-). SAS had been diagnosed in 35.4% of the COVID-19+ subjects, but only 231 (2.7%) of the 8,693 COVID-19- subjects. COVID-19+ subjects were more susceptible to FLU (35.4%) compared to COVID-19- subjects (3.0%). A multivariate analysis revealed that higher risks of COVID-19+ were linked to the following factors: going out without a face mask (OR 7.05, 95% CI 4.53-11.00), FLU+ (OR 6.33, 95% CI 3.80-10.54), excessive exercise before going to sleep (OR 2.10, 95% CI 1.63-2.70), SAS+ (OR 5.08, 95% CI 2.88-8.94), younger age (OR 1.05, 95% CI 1.03-1.07), falling sleep while sitting or talking with someone (OR 3.70, 95% CI 2.30-5.95), and use of hypnotics (OR 2.28, 95% CI 1.20-4.30). Since sleep impairment played a relatively small role in COVID-19+/SAS- subjects, we assume that SAS itself was a more significant risk factor for COVID-19 infection rather than sleep impairment. A better understanding of the mechanisms that result in increased susceptibility to COVID-19 in SAS is vital for helping prevent COVID-19.

Brain Mast Cells in Sleep and Behavioral Regulation.

The function of mast cells in the brain for the mediation of neurobehavior is largely unknown. Mast cells are a heterogeneous population of granulocytic cells in the immune system. Mast cells contain numerous mediators, such as histamine, serotonin, cytokines, chemokines, and lipid-derived factors. Mast cells localize not only in the periphery but are also resident in the brain of mammalians. Mast cells in the brain are constitutively active, releasing their contents gradually or rapidly by anaphylactic degranulation. Their activity is also increased by a wide range of stimuli including both immune and non-immune signals. Brain mast cell neuromodulation may thus be involved in various neurobehavior in health and diseases.Using Kit mutant mast cell deficient mice (KitW/KitW-v), we obtained results indicating that brain mast cells regulate sleep/wake and other behavioral phenotypes and that histamine from brain mast cells promotes wakefulness. These findings were also confirmed using a newer inducible and Kit-independent mast cell deficient Mas-TRECK (toxin receptor knockout) mouse. Injections of diphtheria toxin (DT) selectively deplete mast cells and reduce wakefulness during the periods of mast cell depletion.We recently introduced a mouse model for chronic sleep loss associated with diabetes. The mice reared on the wire net for 3 weeks (i.e., mild stress [MS]) showed decreased amount of non-rapid eye movement (NREM) sleep, increased sleep fragmentation, and abnormal glucose tolerance test [GTT] and insulin tolerance test [ITT], phenotypes which mirror human chronic insomnia. Interestingly, these mice with insomnia showed an increased number of mast cells in both the brain and adipose tissue. Mast cell deficient mice (KitW/KitW-v) and inhibition of mast cell functions with cromolyn or a histamine H1 receptor antagonist administration ameliorated both insomnia and abnormal glycometabolism. Mast cells may therefore represent an important pathophysiological mediator in sleep impairments and abnormal glycometabolism associated with chronic insomnia.

Advances in the pharmacological management of non-24-h sleep-wake disorder.

Introduction: Melatonin, a hormone that regulates circadian rhythms and the sleep-wake cycle, is produced mainly during the dark period in the pineal gland and is suppressed by light exposure. Patients with non-24-h sleep-wake disorder (non-24) fail to entrain the master clock with the 24-h light-dark cycle due to the lack of light perception to the suprachiasmatic nucleus typically in totally blind individuals or other organic disorders in sighted individuals, causing a progressive delay in the sleep-wake cycle and periodic insomnia and daytime sleepiness.Areas covered: Herein, the authors review the pharmacological therapies including exogenous melatonin and melatonin receptor agonists for the management of non-24. They introduce a historical report about the effects of melatonin on the phase shift and entrainment for blind individuals with the free-running circadian rhythm.Expert opinion: Orally administered melatonin entrains the endogenous circadian rhythm and improves nighttime sleep and daytime alertness for non-24. Currently, tasimelteon is the only approved medication for non-24 by the US Food and Drug Administration and the European Medicines Agency. Treatments that focus only on sleep problems are insufficient for the treatment of non-24, and aids to entrain the free-running rhythm with the light-dark cycle are needed.

Reviewing the systematic reviews in OSA surgery.

OBJECTIVE: There is an extensive amount of literature on surgeries as treatment for obstructive sleep apnea syndrome on adults. Previous systematic reviews have been performed to summarize the outcomes for sleep surgeries, with conflicting results. The objective of this study was to critically evaluate these systematic reviews to provide an overview of their quality, strengths, and conclusions. DATA SOURCES: MEDLINE, Scopus, and the Cochrane Collaboration databases were searched from inception to April 2013. REVIEW METHODS: An overview of systematic reviews was undertaken. Studies included in this review are the systematic reviews whose primary objective was to evaluate the outcomes of sleep apnea surgery on adults. The methodological quality of the studies was analyzed with AMSTAR checklist, and the quality of evidence was evaluated using the GRADE assessment tool. Primary outcome measures assessed the effect of surgery on snoring, sleepiness, and the apnea-hypopnea index. RESULTS: A total of 11 studies were included in this study, and the pooled overview includes 378 studies. The systematic reviews were mostly graded as low quality using the GRADE tool and low to moderate according to the AMSTAR checklist. Outcome for apnea-hypopnea index demonstrated substantial variation leading to conflicting results. Despite a high amount of heterogeneity, outcomes for sleepiness and snoring demonstrated significant improvement across included reviews. CONCLUSIONS: Although obstructive sleep apnea surgery is associated with improved outcomes in most studies, the level and quality of evidence reviews requires improvement.