Changes in pharyngeal anatomy and apnea/hypopnea index after a mandibular advancement device.

Objectives: This study aimed to evaluate the therapeutic effcacy of custom-made mandibular advancement devices (MAD) in the control of primary snoring and sleep apnea and to correlate with anatomical changes identified through imaging tests. Methods: Patients (n = 17) diagnosed with sleep apnea or primary snoring were included in this study and subsequently treated with MADs. Changes were assessed using a polysomnographic study (PSG), the Epworth Sleepiness Scale (ESS), and an imaging study with computed tomography scanning (CT). Studies were performed before and after the use of MAD. Anteroposterior measurements were taken in the sagittal plane at the hard palate, glottis, and supraglottic levels along the hard palate axis. Afterward, measurements were taken in the axial plane at the same levels along the hard palate axis. Results: From the six recorded measurements, the airway caliber increased by five. However, these changes were significant only in two measurements (sagittal hard palate and axial supraglottic). Snoring was controlled in 16 of the 17 subjects. From these sixteen, 12 subjects had a correct opening of the airway at the hard palate level. Moreover, daytime sleepiness decreased in all subjects. Discussion: Present results suggest that sagittal hard palate and axial supraglottic opening after use of MAD are mainly responsible for eliminating snoring and improve sleep apnea.

Further Evidence of the Melatonin Calmodulin Interaction: Effect on CaMKII Activity.

Melatonin (MEL) is a pleiotropic indolamine that reaches multiple intracellular targets. Among these, MEL binds to calmodulin (CaM) with high affinity. In presence of Ca2+, CaM binds to CaM-dependent kinase II (CaMKII). The Ca2+-CaM/CaMKII pathway regulates a myriad of brain functions in different cellular compartments. Evidence showing the regulation of this cellular pathway by MEL is scarce. Thus, our main objective was to study the interaction of MEL with CaM and its effects on CaMKII activity in two microenvironments (aqueous and lipidic) naturally occurring within the cell. In addition, colocalization of MEL with CaM in vivo was explored in mice brain hippocampus. In vitro CaM-MEL interaction and the structural conformations of CaM in the presence of this indoleamine were assessed through electrophoretic mobility and isoelectric point. The functional consequence of this interaction was evaluated by measuring CaMKII activity. Ca2+-CaM-MEL increased the activity of CaMKII in aqueous buffer but reduced the kinase activity in lipid buffer. Importantly, MEL colocalizes in vivo with Ca2+-CaM in the hippocampus. Our evidence suggests that MEL regulates the key cellular Ca2+-CaM/CaMKII pathway and might explain why physiological MEL concentrations reduce CaMKII activity in some experimental conditions, while in others it drives biological processes through activation of this kinase.

Metabolic Disturbances Induced by Sleep Restriction as Potential Triggers for Alzheimer's Disease.

Sleep has a major role in learning, memory consolidation, and metabolic function. Although it is known that sleep restriction increases the accumulation of amyloid ß peptide (Aß) and the risk to develop Alzheimer's disease (AD), the mechanism behind these effects remains unknown. In this review, we discuss how chronic sleep restriction induces metabolic and cognitive impairments that could result in the development of AD in late life. Here, we integrate evidence regarding mechanisms whereby metabolic signaling becomes disturbed after short or chronic sleep restriction in the context of cognitive impairment, particularly in the accumulation of Aß in the brain. We also discuss the role of the blood-brain barrier in sleep restriction with an emphasis on the transport of metabolic signals into the brain and Aß clearance. This review presents the unexplored possibility that the alteration of peripheral metabolic signals induced by sleep restriction, especially insulin resistance, is responsible for cognitive deficit and, subsequently, implicated in AD development.

Sleep and Mental Health Disturbances Due to Social Isolation during the COVID-19 Pandemic in Mexico.

The coronavirus disease (COVID-19) that broke out in China in December 2019 rapidly became a worldwide pandemic. In Mexico, the conditions requiring the declaration of a sanitary emergency were reached by the last week of March 2020, and health authorities' limited mobility and imposed social isolation were the main strategies to keep the virus from spreading. Thus, daily living conditions changed drastically in a few days, generating a stressful situation characterized by an almost complete lack of mobility, social isolation, and forced full-time interactions with family members. Soon, complaints of sleep disturbances, anxiety, and symptoms of depression were reported. The present study reports the results of an online survey performed during the first two months of isolation. Questionnaires exploring sleep disturbances, anxiety, and depression were sent to people who responded to an open invitation. A total of 1230 participants filled out the sleep questionnaire, 812 responded to the anxiety questionnaire, and 814 responded to the depression questionnaire. Both men and women reported poor sleep quality, but women showed a higher proportion (79%) than men (60%); young women were more likely to be affected by social isolation. Concerning anxiety and depression, both sexes reported high similar symptoms. These data suggest that stressful conditions related to social isolation and the economic uncertainty caused by the pandemic may induce mental health disturbances, which may become worse with sleep restriction.

Diverse sleep patterns, psychiatric disorders, and perceived stress in inhalants users living on the streets of Mexico City.

Homeless people face stressful circumstances influencing drug consumption, mental health, and sleep disorders. We performed an interdisciplinary study involving psychometric, polysomnographic, and ethnographic records to relate stress, psychiatric disorders, drug consumption, and sleep in ten people (four women, M = 32 y/o) living on the streets of Mexico City. Toluene-based inhalant dependence and suicidality were the more common psychiatric disorders among participants. They also presented sleep fragmentation; some manifested insomnia or sleep restriction, whereas others displayed extended rapid-eye movement sleep latencies associated with depression or inhalant consumption. Inhalants are used to improve mood, strengthen social bonds, and induce either sleep or alertness during the night. Inter-individual distinctions may be related to differential levels of intoxication, stress perception, backgrounds, and abilities to live and sleep on the street. Sleep restriction seems to be the more common factor, which may enhance the negative consequences of street situation.

Chronic sleep loss disrupts blood-testis and blood-epididymis barriers, and reduces male fertility.

Sleep loss increases blood-brain barrier permeability. As the blood-brain barrier and the blood-tissue barriers in the reproductive tract (blood-testis and blood-epididymis barriers) share common characteristics, we hypothesized that sleep restriction may also modify their barrier function. Previous reports showed that sleep loss decreased sperm viability and progressive fast mobility, which may be a consequence of altered blood-testis and blood-epididymis barrier. Therefore, we quantified changes in blood-testis and blood-epididymis barrier after sleep loss and related them to male fertility. Adult male Wistar rats were sleep restricted using the multiple-platform technique in a protocol of 20 hr daily sleep deprivation plus 4 hr of sleep recovery in the home-cage. At the 10th day, barrier permeability assays were performed with Na-fluorescein, 10 kDa Cascade blue-dextrans and Evans blue, and the expression of tight junction proteins, actin and androgen receptor was quantified. At the 10th day of sleep restriction and after sleep recovery days 1-7, males were placed with sexually receptive females, sexual behaviour was tested, and the percentage of pregnancies was calculated. Sleep restriction increased the barrier permeability to low- and high-molecular-weight tracers, and decreased the expression of tight junction proteins, actin and androgen receptor. Concomitantly, sleep restriction reduced the percentage of ejaculating males and the number of pregnancies. Sleep recovery for 2-3 days progressively re-established fertility, as indicated by a higher percentage of ejaculating males and impregnated females. In conclusion, chronic sleep loss alters fertility concomitantly with the disruption of the blood-tissue barriers at the reproductive tract, the mechanism involves androgen signalling.

Cyclic alternating pattern in infants with congenital hypothyroidism.

Congenital hypothyroidism is defined as thyroid hormone deficiency present at birth which is crucial for brain development. Recently, the cyclic alternating pattern, a rhythm present in electroencephalography recordings in non-Rapid eye movement sleep, has been related to brain development and cognition in different pediatric conditions. Therefore, we evaluated the cyclic alternating pattern rate in infants with congenital hypothyroidism, thyroxine supplementation, and healthy controls. The parameters of the cyclic alternating pattern were evaluated in 19 healthy infants (10 female, mean age 25.5 ±â€¯15.5 months) and 21 infants diagnosed with congenital hypothyroidism (19 female, mean age 24.3 ±â€¯19.0 months). We considered the transient electro-cortical activations (phase A of the cycle) in non-Rapid eye movement sleep and the subdivisions of the A phase in: A1, A2 and A3, based on their frequency content. All subjects were subjected to polysomnography recording in a standard laboratory setting. Sleep data were stored computer following the International 10-20 System. Data showed that congenital hypothyroidism infants exhibited higher frequency of central apnea, hypopnea, and arousals in comparison to controls. Particularly, central apnea index decreased with age in the control group but not in congenital hypothyroidism group. Regarding to cyclic alternating pattern measurements, congenital hypothyroidism infants exhibit a higher frequency in the percentage of A3 subtype (electroencephalographic desynchrony) and conversely a lower percentage of A1 subtype (electroencephalographic synchrony), than healthy infants. An important finding of this study is the positive correlation between A1 mean duration and age, which is bigger in control group than in congenital hypothyroidism group (time duration in control group (0.52 s/month) versus congenital hypothyroidism group (0.1 s/month). Infants with congenital hypothyroidism showed an increase of A3 subtype, of central apnea, and of arousals. The reduction of percentage and mean duration of A1 subtype could be a valuable indicator of sleep development in patients with congenital hypothyroidism and healthy infants.

Postnatal overnutrition alters the orexigenic effects of melanin-concentrating hormone (MCH) and reduces MCHR1 hypothalamic expression on spontaneous feeding and fasting.

One of the approaches to induce obesity in rodents consists in reducing litter size to 3 pups during the lactation period. Animals submitted to this manipulation are heavier, hyperphagic and develop several metabolic diseases for the rest of their lives. In the present study, under the premise that melanin-concentrating hormone (MCH), an orexigenic peptide synthesized by neurons of the lateral hypothalamus, is involved in food intake regulation, we aimed to measure the hypothalamic expression of its receptor, MCHR1, in adult early overfed obese animals and normoweight controls at both ad libitum and food deprived conditions. Additionally, we administered MCH, or an antiMCH antibody, into the third ventricle of ad libitum-fed rats, or fasted rats, respectively, and evaluated chow consumption. Typical nocturnal hyperphagia in rodents was elevated in obese animals compared to normoweight controls, accompanied by a lower expression of MCHR1 and leptin receptor (Ob-R). Following a 24 h fasting, MCHR1 remained lower in SL rats. After 4 h of re-feeding, obese animals ate more than normoweight controls. MCH failed to enhance appetite in early overfed obese animals and immunoneutralization of the peptide only reduced fasted induced-hyperphagia in normoweight controls. These results support the notion that both peptide and brain endogenous MCH exert a physiological relevant action in food intake regulation in normoweight rats, but that postnatal overnutrition disturbs this system, as reflected by MCHR1 downregulation at both ad libitum and fasted conditions and in the lack of response to MCH in both positive- and negative-energetic states in early overfed obese animals.

Innate immunity modulation in the duodenal mucosa induced by REM sleep deprivation during infection with Trichinella spirallis.

Sleep is considered to be an important predictor of the immunity, since the absence of sleep can affect the development of the immune response, and consequently increase the susceptibility to contract an infection. The aim of the present study was to investigate if sleep deprivation and stress induce dysregulation of the duodenal mucous membrane during the acute infection with Trichinella spiralis. Our results shows that, in the intestinal mucous membrane, stress and sleep deprivation, produces different effect in the cells, and this effect depends on the studied duodenal compartment, glands or villi. The sleep deprivation affect mast cells mainly, and the stress response is more heterogeneous. Interestingly, in the duodenal mucous membrane, none population of cells in the infected groups responded equally to both conditions. These findings suggest that the response of the intestinal mucous membrane during the infection caused for T. spiralis turns out to be affected in the sleep-deprived rats, therefore, the results of the present study sustain the theory that sleep is a fundamental process that is capable of modulating the immune response of mucous membranes, particularly the one generated against the parasite Trichinella spiralis.

A2A Adenosine Receptor Antagonism Reverts the Blood-Brain Barrier Dysfunction Induced by Sleep Restriction.

Chronic sleep restriction induces blood-brain barrier disruption and increases pro-inflammatory mediators in rodents. Those inflammatory mediators may modulate the blood-brain barrier and constitute a link between sleep loss and blood-brain barrier physiology. We propose that adenosine action on its A2A receptor may be modulating the blood-brain barrier dynamics in sleep-restricted rats. We administrated a selective A2A adenosine receptor antagonist (SCH58261) in sleep-restricted rats at the 10th day of sleep restriction and evaluated the blood-brain barrier permeability to dextrans coupled to fluorescein (FITC-dextrans) and Evans blue. In addition, we evaluated by western blot the expression of tight junction proteins (claudin-5, occludin, ZO-1), adherens junction protein (E-cadherin), A2A adenosine receptor, adenosine-synthesizing enzyme (CD73), and neuroinflammatory markers (Iba-1 and GFAP) in the cerebral cortex, hippocampus, basal nuclei and cerebellar vermis. Sleep restriction increased blood-brain barrier permeability to FITC-dextrans and Evans blue, and the effect was reverted by the administration of SCH58261 in almost all brain regions, excluding the cerebellum. Sleep restriction increased the expression of A2A adenosine receptor only in the hippocampus and basal nuclei without changing the expression of CD73 in all brain regions. Sleep restriction reduced the expression of tight junction proteins in all brain regions, except in the cerebellum; and SCH58261 restored the levels of tight junction proteins in the cortex, hippocampus and basal nuclei. Finally, sleep restriction induced GFAP and Iba-1 overexpression that was attenuated with the administration of SCH58261. These data suggest that the action of adenosine on its A2A receptor may have a crucial role in blood-brain barrier dysfunction during sleep loss probably by direct modulation of brain endothelial cell permeability or through a mechanism that involves gliosis with subsequent inflammation and increased blood-brain barrier permeability.

The Bidirectional Relationship between Sleep and Immunity against Infections.

Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The function of sleep in altering immune responses must be determined to understand how sleep deprivation increases the susceptibility to viral, bacterial, and parasitic infections. There are several explanations for greater susceptibility to infections after reduced sleep, such as impaired mitogenic proliferation of lymphocytes, decreased HLA-DR expression, the upregulation of CD14+, and variations in CD4+ and CD8+ T lymphocytes, which have been observed during partial sleep deprivation. Also, steroid hormones, in addition to regulating sexual behavior, influence sleep. Thus, we hypothesize that sleep and the immune-endocrine system have a bidirectional relationship in governing various physiological processes, including immunity to infections. This review discusses the evidence on the bidirectional effects of the immune response against viral, bacterial, and parasitic infections on sleep patterns and how the lack of sleep affects the immune response against such agents. Because sleep is essential in the maintenance of homeostasis, these situations must be adapted to elicit changes in sleep patterns and other physiological parameters during the immune response to infections to which the organism is continuously exposed.

Sleep deprivation induces changes in immunity in Trichinella spiralis-infected rats.

Sleep is considered an important predictor of immunity. A lack of sleep may reduce immunity, which increases susceptibility to any type of infection. Moreover, sleep deprivation in humans produces changes in both, the percent of circulating immune cells (T cells and NK cells) and cytokine levels (IL-1, IFNγ, TNΦ-αα, IL-6 and IL-17). The aim of our study was to investigate whether sleep deprivation produces deregulation on immune variables during the immune response generated against the helminth parasite Trichinella spiralis. Because sleep deprivation is stressful per se, we designed another experiments to compared stress alone (consisting in movement restriction and single housing) with sleep deprivation, in both control (uninfected) and experimental (infected) rats. Our results demonstrate that the sleep deprivation and stress have a differential effect in mesenteric lymph nodes (MLN) and spleen. In uninfected rats sleep deprivation alone produces an increase in natural killer cells (NK+) and B cells (CD45+), accompanied by a decrease in cytotoxic T cells (CD3+CD8+) in spleen; while, in MLN, produces only an increase in natural killer cells (NK+). Both, SD and stress, produce an increased percentage of total T cells (CD3+) in spleen. In the MLN both are also associated to an increase in cytotoxic T cells (CD3+CD8+) and B cells (CD45+). In the spleens of parasitized rats, cell populations did not change. In spleens of both, sleep-deprived and stressed infected rats, we observed an increase in B cells (CD45+). In infected rats, sleep deprivation alone produced an increase in NK cells (NK+). In mesenteric node cell populations of parasitized rats, we observed a decrease in NK cells and an increase in T helper (CD4+) cells in both SD and stressed rats. Rats that were only subjected to stress showed a decrease in B cells (CD45+). These findings suggest that the immune response generated against infection caused by T. spiralis is affected when the sleep pattern is disrupted. These results support the notion that sleep is a fundamental process for an adequate and strong immune response generated against this parasite.

Social and Cultural Elements Associated with Neurocognitive Dysfunctions in Spinocerebellar Ataxia Type 2 Patients.

Spinocerebellar Ataxia Type 2 (SCA2) is a rare genetic disorder producing cerebellar degeneration and affecting motor abilities. Neuroimaging studies also show neurodegeneration in subcortical and cortical regions related to emotional and social processes. From social neuroscience, it is suggested that motor and social abilities can be influenced by particular cultural dynamics so, culture is fundamental to understand the effect of brain-related alterations. Here, we present the first analysis about the cultural elements related to the SCA2 disorder in 15 patients previously evaluated with neuroimaging and psychometric instruments, and their nuclear relationships distributed in six geographical and cultural regions in Mexico. Ethnographic records and photographic and video archives about the quotidian participant's routine were obtained from the patients, their relatives and their caregivers. The information was categorized and interpreted taking into consideration cultural issues and patients' medical files. Our analyses suggest that most of the participants do not understand the nature of the disease and this misunderstanding favors magic and non-medical explanations. Patients' testimonies suggest a decrease in pain perception as well as motor alterations that may be related to interoceptive dysfunctions. Relatives' testimonies indicate patients' lack of social and emotional interests that may be related to frontal, temporal, and cerebellar degeneration. In general, participants use their religious beliefs to deal with the disease and only a few of them trust the health system. Patients and their families are either openly rejected and ignored, tolerated or even helped by their community accordingly to different regional traits. We propose that ethnography can provide social representations to understand the patients' alterations, to formulate neurobiological hypotheses, to develop neurocognitive interventions, and to improve the medical approach to the disease.

Reduced systemic levels of IL-10 are associated with the severity of obstructive sleep apnea and insulin resistance in morbidly obese humans.

Obstructive sleep apnea (OSA) has been related to elevation of inflammatory cytokines and development of insulin resistance in morbidly obese (MO) subjects. However, it is still unclear whether the systemic concentration of anti-inflammatory mediators is also affected in MO subjects directly related to the severity of OSA and level of insulin resistance. Normal weight and MO subjects were subjected to overnight polysomnography in order to establish the severity of OSA, according to the apnea-hypopnea index (AHI). Blood samples were obtained for estimation of total cholesterol and triglycerides, insulin, glucose, insulin resistance, tumor necrosis factor alpha (TNF-α), interleukin 12 (IL12), and interleukin 10 (IL-10). Serum levels of IL-10 were significantly lower in MO subjects with OSA than in MO and control individuals without OSA. Besides being inversely associated with serum TNF-α and IL-12, decreased IL-10 levels were significantly related to increased AHI, hyperinsulinemia, and insulin resistance. Serum IL-10 is significantly reduced in morbidly obese subjects with severe OSA while also showing a clear relationship with a state of hyperinsulinemia and insulin resistance probably regardless of obesity in the present sample. It may be of potential clinical interest to identify the stimulatory mechanisms of IL-10 in obese individuals with OSA.

Sleep in the spider monkey (Ateles geoffroyi): A semi-restrictive, non-invasive, polysomnographic study.

The normal sleep patterns of the spider monkey (Ateles geoffroyi) have not been described yet. The objective of this study was to characterize the electrophysiological patterns, sleeping postures, and sleep-wake cycle in semi-restricted spider monkeys. Continuous 24-hr polysomnographic (PSG) recordings, involving simultaneous recording of non-invasive electroencephalographic (EEG), electro-oculographic (EOG), and electromyographic (EMG) activities, were carried out in captive monkeys living in outdoor rainforest enclosures. Electrode placement was done according to the human international 10-20 system. Specific behaviors displayed by monkeys during the sleep-wake cycles were correlated with the PSG recordings. The nycthemeral distribution of the sleep-wake cycle was also calculated. The results show that electrophysiological N-REM sleep patterns in spider monkeys are similar to those observed in other primates, including human beings. Furthermore, a vertical semi-fetal posture was observed during N-REM and REM sleep phases. The amount of nocturnal sleep was significantly higher than that of the diurnal period, showing that the spider monkey is a diurnal primate. An outstanding finding was the absence of muscular atonia during the spider monkey's REM sleep, which suggests that arboreal primates have developed a neuromuscular mechanism specialized for sleeping in a vertical posture.

Further definition on the multiple partner choice arena: a potential animal model for the study of premature ejaculation.

INTRODUCTION: The multiple partner choice arena (MPCA) is an experimental setup in which male rats display a significant shortening of ejaculation latency, which is the main characteristic of premature ejaculation (PE) in men. Thus, the MPCA is a potential animal model for PE. AIM: In this study, we further analyze whether the features of the MPCA satisfy the validity criteria for it to be considered an animal model as well as the possible participation of the serotoninergic system in the faster ejaculation exhibited by male rats in the MPCA. METHODS: In Experiment 1, male rats were tested in a standard arena to assess their sexual behavior, then were assessed 1 week later in the MPCA. Another group was first tested in the MPCA, then in a standard arena. In Experiment 2, male rats divided into two groups were treated daily with WAY-100635 (5-HT(1A) antagonist) or vehicle for 15 days. In each group, half of the subjects were tested in a standard arena and half were tested in the MPCA on days 1, 8, and 15 of treatment. MAIN OUTCOME MEASURES: Number of intromissions and intromission and ejaculation latencies were the main outcome measures. RESULTS: In Experiment 1, males tested in the MPCA ejaculated significantly faster, regardless of the order in which they were evaluated in both arenas. In Experiment 2, the administration of WAY-100635 increased intromission and ejaculation latencies, and the number of intromissions in the MPCA. CONCLUSIONS: The results obtained in the MPCA support its use as an animal model for PE evaluation.

D1-like antagonist blocks conditioned place preference induced by ejaculation in male rats.

Mating behavior, particularly ejaculation, induces a state of sexual reward, which is evaluated by the conditioned place preference test. Several studies have shown that opioid receptors are involved in inducing the state of sexual reward, mainly because this state is blocked with naloxone, a mu opioid receptor antagonist. Dopamine has been implicated in sexual motivation, coital behavior and sexual reward, however, some experiments show that D2-like or non-specific dopaminergic antagonists are not capable of blocking the conditioned place preference induced by ejaculation; therefore, the role of dopamine on sexual reward has not been demonstrated, or has been frequently discarded. We show that a dose of SCH 23390 (a specific dopamine D1-like receptor antagonist), which does not modify locomotion, blocks the conditioned place preference induced by ejaculation and the conditioned place preference induced by SKF 38393 (D1-like agonist). Our results indicate that dopamine, across the D1-like receptors, is involved in the sexual reward induced by ejaculation.

Sleep loss as a factor to induce cellular and molecular inflammatory variations.

A reduction in the amount of time spent sleeping occurs chronically in modern society. Clinical and experimental studies in humans and animal models have shown that immune function is impaired when sleep loss is experienced. Sleep loss exerts a strong regulatory influence on peripheral levels of inflammatory mediators of the immune response. An increasing number of research projects support the existence of reciprocal regulation between sleep and low-intensity inflammatory response. Recent studies show that sleep deficient humans and rodents exhibit a proinflammatory component; therefore, sleep loss is considered as a risk factor for developing cardiovascular, metabolic, and neurodegenerative diseases (e.g., diabetes, Alzheimer's disease, and multiple sclerosis). Circulating levels of proinflammatory mediators depend on the intensity and duration of the method employed to induce sleep loss. Recognizing the fact that the concentration of proinflammatory mediators is different between acute and chronic sleep-loss may expand the understanding of the relationship between sleep and the immune response. The aim of this review is to integrate data from recent published reports (2002-2013) on the effects of sleep loss on the immune response. This review may allow readers to have an integrated view of the mechanisms involved in central and peripheral deficits induced by sleep loss.