Exploring the molecular pathways linking sleep phenotypes and POGZ-associated neurodevelopmental disorder.

Pogo transposable element-derived protein with ZNF domain (POGZ) gene encodes a chromatin regulator and rare variants on this gene have been associated with a broad spectrum of neurodevelopmental disorders, such as White-Sutton syndrome. Patient clinical manifestations frequently include developmental delay, autism spectrum disorder and obesity. Sleep disturbances are also commonly observed in these patients, yet the biological pathways which link sleep traits to the POGZ-associated syndrome remain unclear. We screened for sleep implications among individuals with causative POGZ variants previously described. Sleep disturbances were observed in 52% of patients, and being obese was not observed as a risk factor for sleep problems. Next, we identified genes associated with sleep-associated traits among the POGZ regulatory targets, aiming to uncover the molecular pathways that, when disrupted by POGZ loss of function, contribute to the aetiology of sleep phenotypes in these patients. The intersect between POGZ targets and sleep-related genes was used in a pathway enrichment analysis. Relevant pathways among these overlapping genes are involved in the regulation of circadian rhythm, tau protein binding, ATPase activator activity. This study may represent the beginning for novel functional investigations on shared molecular mechanisms between sleep disturbances and rare developmental syndromes related to POGZ and its regulatory targets.

Understanding Sexual Parasomnias: A Review of the Current Literature on Their Nature, Diagnosis, Impacts, and Management.

Sexual behavior during sleep, known as sexual parasomnias, has captured the interest of researchers and clinicians. These parasomnias involve various sexual activities that occur unconsciously during sleep. Although relatively rare, they can profoundly affect well-being and relationships and can carry legal consequences. Understanding their nature, prevalence, and causes is crucial for advancing knowledge in this field. This article revisits the topic of sexsomnia, presenting new data and discussing cases published from 2007 to 2023. By analyzing these cases, we aim to enhance recognition, diagnosis, and management of sexsomnia, reducing stigma and providing better support for affected individuals.

A cross-sectional analysis of the association between sleep disorders and cancer using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2014.

STUDY OBJECTIVES: Cancer is one of the main causes of death in the world, while sleep disorders are a serious public health problem, especially in large cities, insomnia and obstructive sleep apnea (OSA) being the most common. In the last decade, studies have pointed to a possible association between sleep disorders and cancer. The aim of this study is to evaluate whether there is any association between sleep disorders and cancer diagnosis. METHODS: Five National Health and Nutrition Examination Surveys (NHANES) (2005-2014) from the United States were combined in order to obtain the sample. Two main sleep variables were assessed: having trouble sleeping and/or ever telling a doctor you had a sleep problem. The odds ratio of ever having a cancer diagnosis was the main outcome. Data was analyzed by binary logistic regression models in Jamovi. RESULTS: The final sample comprised 26,821 participants. Individuals who reported having trouble sleeping had an odds ratio (OR)=1.48 (95% CI=[1.336-1.646]; p<0.001) of having been diagnosed with cancer, and those who had already been diagnosed with a sleep disorder presented an OR=1.21 (95% CI=[1.046-1.415]; p=0.011), showing an increased chance of having been diagnosed with cancer. In men, these values were even greater, presenting an OR=1.56 (95% CI=[1.321-1.843]; p<0.001) and an OR=1.26 (95% CI=[1.013-1.582]; p=0.037), respectively, for having trouble sleeping and for having been diagnosed with a sleep disorders, in relation to having been diagnosed with cancer. CONCLUSIONS: Individuals who had trouble sleeping or who had been diagnosed with a sleep disorder at any time in their life were more likely to have been diagnosed with cancer.

Methods for REM Sleep Density Analysis: A Scoping Review.

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.

Emergence of different dimensions of sleepiness in a general population sample: An EPISONO study.

INTRODUCTION: Recent evidence supports the idea that sleepiness has several dimensions, comprising psychophysiological phenomena, such as sleep propensity and sleepiness perception. The Epworth Sleepiness Scale (ESS) is among one of the most used sleepiness assessment tools, but recent data suggest that it might not detect problematic impairments in sleep health. More research is warranted investigating sleepiness dimensions with large sample sizes, using both objective and subjective methods of analyzing sleep. METHODS: We used data from the Epidemiological Sleep Study (EPISONO), a major study carried out in Brazil using a representative sample of 1042 participants of the general population of Sao Paulo city, who completed questionnaires and underwent type I polysomnography. Sleepiness was measured by the ESS (sleep propensity) and the UNIFESP Sleep Questionnaire, which asked about the frequency of feeling sleepy during the day (sleepiness perception). The participants were distributed into 4 groups in respect of excessive daytime sleepiness (EDS) according to the following criteria: 1) having an ESS score >10 (ESS group). 2) feeling sleepy ≥3 times per week (Frequent EDS group). 3) the combined criteria (Combined EDS group). 4) having no evidence of EDS (no EDS group). The UNIFESP Sleep Questionnaire was used to obtain self-reported sleep duration, sleep debt, and sleep duration variability. Participants also completed the Pittsburgh Sleep Quality Index, the Insomnia Severity Index, and a pre-polysomnography sleep questionnaire. RESULTS: After removing participants with missing data, there were 620 participants with no EDS, 255 individuals in the ESS group, 68 in the Frequent EDS group, and 73 in the Combined EDS group. Compared to the no EDS group, the ESS and Combined EDS groups had significantly increased sleep efficiency, diminished sleep latency, wake after sleep onset, and self-reported weekly sleep duration. The Frequent and Combined EDS groups had significantly higher scores in the Insomnia Severity Index and Pittsburgh Sleep Quality Index. All EDS groups had an increased likelihood of nonrestorative sleep. EDS frequency and the ESS scores were significantly correlated. CONCLUSIONS: Participants with a high sleep propensity had a profile suggesting prior sleep deprivation, while high sleepiness perception was associated with impaired sleep quality. These findings indicated that, in the general population, these instruments evaluated separate sleepiness dimensions with different associations, highlighting that screening using a combination of instruments might be more effective in detecting impairments in sleep health.

Impact of the early months of the COVID-19 pandemic on the sleep patterns of a Brazilian population sample.

Humanitarian and health crisis have drastic effects on the physical and mental well-being of people. The COVID-19 pandemic forced many countries to impose containment measures on its population to halt the spread of the new coronavirus (SARS-CoV-2). This aim of this study was to explore self-reported sleep quality and insomnia symptoms in a sample of the Brazilian population before and during the COVID-19 quarantine period. Our data was collected through online questionnaires, including the Pittsburgh Sleep Quality Index, the Insomnia Severity Index, and the Sleep Hygiene Index. The final sample comprised 1,109 volunteers. Generalized estimating equations (GEE) revealed that during the initial months of the COVID-19 pandemic, alterations in self-reported sleep parameters were observed in the participants. Sleep efficiency and sleep duration increased, but there was a worsening in sleep quality and an increase in symptoms related to insomnia.

The role of upper airway and facial skeleton anatomy in the evolution of obstructive sleep apnea: an 8-year follow-up.

PURPOSE: To evaluate the role of anatomic alterations of the upper airway and facial skeleton in the evolution of obstructive sleep apnea (OSA) in a prospective population-based study with an 8-year follow-up. METHODS: This was a population-based, longitudinal, prospective study, which took place from 2007 to 2015 at the Instituto do Sono, Sao Paulo, Brazil. In 2007, type I polysomnography (PSG), otorhinolaryngological examination, and collection of anthropometric measurements of all volunteers were performed. Volunteers were classified according to their anatomical features of the upper airway and facial skeleton. After 8 years, volunteers were invited for reevaluation. The relationship between anatomical characteristics and polysomnographic evolution was evaluated. RESULTS: The study included 554 patients. After 8 years of follow-up, there was an increase in neck circumference and body mass index of the participants. There was a worsening in all polysomnographic parameters analyzed, with an increase in the apnea-hypopnea index, a decrease in minimum saturation values, and an increase in the percentage of sleep time with peripheral oxyhemoglobin saturation <90%. There was no statistical relationship between the anatomical findings considered unfavorable and the worsening of polysomnographic parameters. CONCLUSIONS: In a sample of the general population, after 8 years, we did not find any relationship between upper airway and facial skeleton characteristics and the progression of OSA.

The effects of social jetlag and sleep variability on sleepiness in a population-based study: The mediating role of sleep debt.

Sleepiness is a multicausal condition, and previous research has highlighted associations between this symptom and the circadian timing system, specifically concerning social jetlag and sleep variability. Recent inquiries have shown that the effects of social jetlag on sleepiness can be confounded with the consequences of sleep debt. In light of the current evidence, we aimed to assess the effects of social jetlag and sleep variability on sleepiness and the potential mediating role of sleep debt. We used data from the EPISONO study, a cross-sectional population-based study with a sample size of 1042 participants, representative of the city of Sao Paulo, Brazil. Participants completed the UNIFESP Sleep Questionnaire (self-reported bedtime and get-up time) and the Epworth Sleepiness Scale (subjective daytime sleepiness). Subsequently, sleep-corrected mid-sleep time (chronotype), total sleep time, social jetlag (absolute difference between the mid-sleep time on workdays and mid-sleep time on free days), sleep variability (standard deviation of mid-sleep time), and sleep debt (difference between total sleep time on workdays and free days) were calculated. Generalised linear models were used to test whether social jetlag and sleep variability affected sleepiness. Mediation models were used to determine if any observed significant effects were mediated by sleep debt. The prevalence of social jetlag was 23% for >1 h and 12% for >2 h. The mean sleep variability was 41 ± 30 min. Social jetlag had a significant effect on the Epworth Sleepiness Scale scores. This association was no longer statistically significant after controlling for age, sex, body mass index, work schedule, and chronotype. A significant indirect effect of social jetlag on sleep debt and subsequently on the Epworth Sleepiness Scale scores was found. No effect of sleep variability on sleepiness could be identified. In conclusion, the association between social jetlag and sleepiness was mediated by sleep debt but was not independent of demographic, work, and chronotype variables. This study provides new evidence on the importance of circadian misalignment and sleep debt for sleep health on a population level.

Exploring the potential relationships among obstructive sleep apnea, erectile dysfunction, and gut microbiota: a narrative review.

INTRODUCTION: Poor sleep quality is closely associated with comorbidities affecting a multitude of organ systems. Among the sleep disorders in the population, there has recently been an increase in the prevalence of obstructive sleep apnea (OSA), which has particularly affected men. The intermittent hypoxia and sleep fragmentation associated with OSA can result in the manifestation or aggravation of a number of pathophysiologic conditions, including the impairment of reproductive function in men and women. In this context, erectile dysfunction (ED) is of particular concern. Other consequences of OSA are changes in the gastrointestinal microbiota, with the resultant dysbiosis having potentially harmful consequences that promote downstream exacerbation of various comorbidities. OBJECTIVES: This narrative review aims to explore the potential relationships among ED, gut microbiota, and OSA. METHODS: A search of the relevant literature was performed in the PubMed, Embase, Medline, and Web of Science databases. RESULTS: Sleep is important for regulating the body's functions, and sleep deprivation can negatively affect health. OSA can damage organic functions, including reproductive function, and can lead to ED. Restoring the microbiota and improving sleep can help to improve sexual function or reverse ED and enhance other associated conditions mediated through the gut-brain axis relationship. Probiotics and prebiotics can be used as supportive strategies in the prevention and treatment of OSA, as they help to reduce systemic inflammation and improve intestinal barrier function. CONCLUSION: A good diet, a healthy lifestyle, and proper bowel function are essential in controlling depression and several other pathologies. Modulating the gut microbiota through probiotics and prebiotics can provide a viable strategy for developing new therapeutic options in treating many conditions. A better understanding of these a priori unrelated phenomena would foster our understanding of the effects of OSA on human fertility and how changes in gut microbiota may play a role.

Insomnia is associated with symptoms of central sensitization in patients with painful temporomandibular disorders.

BACKGROUND: Central sensitization (CS) and temporomandibular disorder (TMD) are both associated with insomnia. Therefore, the authors aimed to investigate whether insomnia was associated with more symptoms of CS in patients with TMD. METHODS: In 82 volunteers with TMD, insomnia was clinically assessed, allowing sample stratification according to its presence. The Central Sensitization Inventory questionnaire was self-applied to assess the clinical symptoms of CS. RESULTS: Participants with insomnia had significantly higher mean (SD) scores of CS according to the Central Sensitization Inventory than participants without insomnia (43.10 [12.57] vs 26.59 [13.66]; P = < .001). CONCLUSIONS: Insomnia was associated with higher scores of CS symptoms in patients with TMD. PRACTICAL IMPLICATIONS: Insomnia influences TMD as well as its relationship with CS, and, therefore, it is critical to the clinical management of TMD.

Robust specific RBD responses and neutralizing antibodies after ChAdOx1 nCoV-19 and CoronaVac vaccination in SARS-CoV-2- seropositive individuals.

Background: The pandemic unleashed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 500 million people worldwide and caused more than 6 million deaths. Cellular and humoral immunity induced by infection or immunization are key factors in controlling the viral burden and avoiding the recurrence of coronavirus disease. The duration and effectiveness of immunity after infection is relevant to pandemic policy interventions, including the timing of vaccine boosters. Objectives: We sought to evaluate longitudinal binding and functional antibodies against SARS-CoV-2 receptor-binding domain in police officers and health care workers with a history of coronavirus disease 2019 and compare with SARS-CoV-2-naive individuals after vaccination with adenovirus-based ChAdOx1 nCoV-19 (AstraZeneca-Fiocruz) or the inactivated CoronaVac vaccine (Sinovac-Butantan Institute). Methods: A total of 208 participants were vaccinated. Of these, 126 (60.57%) received the ChAdOx1 nCoV-19 vaccine and 82 (39.42%) received the CoronaVac vaccine. Prevaccination and postvaccination blood was collected, and the amount of anti-SARS-CoV-2 IgG and the neutralizing ability of the antibodies to block the interaction between angiotensin-converting enzyme 2 and receptor-binding domain were determined. Results: Subjects with preexisting SARS-CoV-2 immunity and who received a single dose of ChAdOx1 nCoV-19 or CoronaVac have similar or superior antibody levels when compared with levels in seronegative individuals even after 2 doses of the vaccine. Neutralizing antibody titers of seropositive individuals were higher with a single dose of either ChAdOx1 nCoV-19 or CoronaVac compared with those of seronegative individuals. After 2 doses, both groups reached a plateau response. Conclusions: Our data reinforce the importance of vaccine boosters to increase specific binding and neutralizing SARS-CoV-2 antibodies.

The effects of sleep deprivation and obstructive sleep apnea syndrome on male reproductive function: a multi-arm randomised trial.

Sleep is essential for the maintenance of health and systemic homeostasis. Decreased sleep time and sleep quality have been associated with a wide range of diseases. To evaluate the effects of obstructive sleep apnea (OSA) and total or selective rapid eye movement (REM) sleep deprivation on male reproductive function, we performed a three-arm parallel study with one pre-defined OSA group and a group of healthy volunteers who were then randomised into total or REM sleep deprivation groups. Questionnaires were completed and overnight polysomnography was undertaken, and blood and sperm samples were collected at the Sleep Institute, São Paulo, Brazil. OSA was diagnosed using questionnaires and polysomnography. Male sexual function was assessed through the questionnaires, blood tests, and semen samples. Data showed an association between OSA and lower circulating levels of total and free testosterone and high-density lipoproteins, as well as a lower proportion of healthy sperm cells and decreased sperm concentration, in comparison to volunteers. Volunteers subjected to either total or REM sleep deprivation had increased circulating levels of thyroid-stimulating hormone, insulin, and higher homeostatic model assessment of insulin resistance (HOMA-IR) values. Both sleep-deprived groups also shown decreased cholesterol, and low-density lipoproteins when compared to their baseline levels, but had no alterations in their spermograms. We observed a reduction in total testosterone following total sleep deprivation, but no effect after REM sleep deprivation. OSA was associated with a hormonal imbalance, which is probably linked with impaired reproductive function and associated comorbidities, such as sleep fragmentation/loss and obesity.

Association between night pain and quality of life in women: A general population sleep study.

BACKGROUND: Women with pain present decreased sleep duration and quality of life, but little is known about the consequences of nighttime pain on overall health. Our goal was to compare levels of anxiety, depression and fatigue in women with pain during the night with those without pain. We hypothesized that pain perception is associated with the worsening of fatigue and mood. METHODS: In total, 244 women aged 20-80 years who took part in the Epidemiologic Sleep Study (EPISONO) met the inclusion criteria, 85 in the self-reported pain group and 171 in the control group. Participants were assigned to the pain group if they both responded (i) they generally had pain, according to Pre-Sleep Questionnaire (PSQ) and (ii) their pain generally interfered with their sleep 3 or more times a week, according to Pittsburg Sleep Quality Index (PSQI). Those who answered negatively to both questions were allocated to the control group. All participants underwent a full night laboratory polysomnography, and completed questionnaires related to fatigue, depression, anxiety and quality of life. RESULTS: Pain group participants had a significantly lower perception of quality of life, and significantly higher levels of fatigue (5.4 times), anxiety and depression. Pain perception was also correlated to levels of anxiety and depression in the psychological (rs  = -0.463, -0.607, respectively) and social (rs  = -0.423, -0.438, respectively) quality of life domains. CONCLUSIONS: Nighttime pain in women was associated with decreased quality of life, worsening mood and fatigue. Our data shows the importance of investigating pain and its deleterious effects on women's health. SIGNIFICANCE: Our study highlights that women experiencing nighttime pain also reported worse mood outcomes and decreased quality of life, regardless of the level and type of pain. Our data, based on association analysis and not investigating causality, suggest it is important to consider nighttime pain in clinical care to improve quality of life and general health.

The effects of hormonal contraceptive use on sleep in women: A systematic review and meta-analysis.

Hormonal contraceptives are some of the most widely used medications worldwide, but studies on their effects on sleep are contradictory, with some reporting a sleep-promoting effect, while others a sleep-inhibiting effect. Our objective was, therefore, to undertake a systematic review and meta-analysis of the literature on this subject to try to clarify their effects. A search was conducted in three databases (PubMed, Scopus and Web of Science). Only studies evaluating hormonal contraception use were considered eligible, and both objective and subjective sleep-related outcomes were considered. Individual effect size was calculated for each article, and meta-analyses were performed using a DerSimonian and Laird random effects method. The initial search identified 2076 articles, of which 13 met the criteria for the study after full text evaluation. A total of 33 meta-analyses were performed, three of them related to subjective measures and 30 considering data from polysomnography. The only statistically significant result between contraceptive users and non-contraceptive users was observed in respect of wake after sleep onset, which was 7 min shorter among contraceptive users (-7.12 [-12.80; -1.44]; I2  = 65%; p = 0.01). In conclusion, hormonal contraceptives are not associated with clinically relevant changes in sleep patterns in women.

Effect of chronic sleep deprivation on acrosomal integrity and functional parameters of murine sperm.

OBJECTIVE: To evaluate the effect of chronic sleep deprivation on sperm function quality in mice. DESIGN: Experimental study. SETTING: Not applicable. ANIMALS: Spermatozoa from twenty-four 10-week-old C57BL/6J male mice. INTERVENTION(S): The sleep deprivation group underwent gentle handling for 6 hours for 5 consecutive days. The mice in the sleep recovery group were allowed to sleep during the 24-hour period after the sleep deprivation protocol. MAIN OUTCOME MEASURE(S): After euthanasia, the spermatozoa were collected for analysis. Sperm motility was evaluated using computer-assisted sperm analyzer. Intracellular superoxide anion (O2-) activity, acrosome integrity, mitochondrial activity, and DNA fragmentation assays were conducted afterward. RESULT(S): Sleep deprivation and sleep recovery groups presented a lower percentage of spermatozoa with an intact acrosome, compared with the respective control groups. Regarding DNA fragmentation, a decreased proportion of spermatozoa with Comet I class intact DNA was observed in the sleep recovery group, compared with the recovery control group. Beat cross frequency was increased in the sleep recovery group. CONCLUSION(S): Sleep deprivation can reduce sperm quality, impairing acrosome integrity. Sleep recovery decreased DNA integrity and increased beat cross frequency.