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.

The impact on the quality of life and sleep complaints in a vitiligo sample and the influence of inflammatory cytokines in the interaction between vitiligo and sleep.

INTRODUCTION: Vitiligo is an autoimmune dermatosis that affects quality of life, which englobes sleep quality. Sleep regulates the immune system, including inflammatory cytokines, and other pathways, which may influence vitiligo pathogenesis. OBJECTIVES: To analyze levels of immune serum components (cytokines) in a vitiligo group, and assess whether there was any association with sleep. METHODS: This study comprised 30 vitiligo patients and 26 control individuals. Quality of life and sleep questionnaires were completed [Dermatology Life Quality Index (DLQI), Short-Form Health Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI)]. Seven cytokines have been measured: IFN-γ, interleukin (IL)-4, IL-6, IL-10, IL-17A, IL-12 p40 and TNF-α. RESULTS: The mean age of the vitiligo group was 47.7 years-old, with prevalence of females (66.7 %). Mucosal (70 %), acral (60 %) and focal subtype (53.3 %) predominated. Signs of vitiligo activity were identified in 63.3 % of the disease sample. Total PSQI scores and scores for domain 4 (sleep efficiency) were statistically worse in vitiligo group. The SF-36 and ISI total scores were worse in the vitiligo group, although not statistically significant compared with controls. Four SF-36 domains were statistically worse in vitiligo sample, and the DLQI mean score was mild to moderate (5.57). Cytokine levels were not different between groups, or when associated with PSQI. Higher ISI scores (more severe insomnia) were related to increased IL-17A. Higher IL-4, IL-6 and IL-10 levels were associated with previous phototherapy. CONCLUSIONS: Poor sleep and impaired aspects of quality of life predominated in the vitiligo sample. Insomnia was related to IL-17A increase in vitiligo. Increased levels of IL-4, IL-6 and IL-10 were related to previous ultraviolet B narrow band (UVB-NB) phototherapy, suggesting an interaction of this treatment on immune system. Sleep disruption and the course of vitiligo may have common pathways in respect of circadian cytokines, which may represent an important subject in vitiligo management.

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.

Network analysis of sleep bruxism in the EPISONO adult general population.

Sleep bruxism (SB) has been associated with biological and psychosocial factors. The assessment of SB includes self-report, clinical evaluation, and polysomnography. This study aimed to investigate the associations of self-reported SB with other sleep disorders and demographic, psychological, and lifestyle factors in the adult general population, and to investigate whether self-reported SB and polysomnographically (PSG) confirmed SB provide similar outcomes in terms of their associated factors. We recruited 915 adults from the general population in Sao Paulo, Brazil. All participants underwent a one-night PSG recording and answered questions about sex, age, BMI, insomnia, OSA risk, anxiety, depression, average caffeine consumption, smoking frequency, and alcohol consumption frequency. We investigated the link between SB and the other variables in univariate, multivariate, and network models, and we repeated each model once with self-reported SB and once with PSG-confirmed SB. Self-reported SB was only significantly associated with sex (p = 0.042), anxiety (p = 0.002), and depression (p = 0.03) in the univariate analysis, and was associated with insomnia in the univariate (p < 0.001) and multivariate (ß = 1.054, 95%CI 1.018-1.092, p = 0.003) analyses. Network analysis showed that self-reported SB had a direct positive edge to insomnia, while PSG-confirmed SB was not significantly associated with any of the other variables. Thus, sleep bruxism was positively associated with insomnia only when self-reported, while PSG-confirmed SB was not associated with any of the included factors.

Ventilatory Burden as a Measure of Obstructive Sleep Apnea Severity Is Predictive of Cardiovascular and All-Cause Mortality.

Rationale: The apnea-hypopnea index (AHI), used for the diagnosis of obstructive sleep apnea, captures only the frequency of respiratory events and has demonstrable limitations. Objectives: We propose a novel automated measure, termed "ventilatory burden" (VB), that represents the proportion of overnight breaths with less than 50% normalized amplitude, and we show its ability to overcome limitations of AHI. Methods: Data from two epidemiological cohorts (EPISONO [Sao Paolo Epidemiological Study] and SHHS [Sleep Heart Health Study]) and two retrospective clinical cohorts (DAYFUN; New York University Center for Brain Health) were used in this study to 1) derive the normative range of VB, 2) assess the relationship between degree of upper airway obstruction and VB, and 3) assess the relationship between VB and all-cause and cardiovascular disease (CVD) mortality with and without hypoxic burden that was derived using an in-house automated algorithm. Measurements and Main Results: The 95th percentiles of VB in asymptomatic healthy subjects across the EPISONO and the DAYFUN cohorts were 25.2% and 26.7%, respectively (median [interquartile range], VBEPISONO, 5.5 [3.5-9.7]%; VBDAYFUN, 9.8 [6.4-15.6]%). VB was associated with the degree of upper airway obstruction in a dose-response manner (VBuntreated, 31.6 [27.1]%; VBtreated, 7.2 [4.7]%; VBsuboptimally treated, 17.6 [18.7]%; VBoff-treatment, 41.6 [18.1]%) and exhibited low night-to-night variability (intraclass correlation coefficient [2,1], 0.89). VB was predictive of all-cause and CVD mortality in the SHHS cohort before and after adjusting for covariates including hypoxic burden. Although AHI was predictive of all-cause mortality, it was not associated with CVD mortality in the SHHS cohort. Conclusions: Automated VB can effectively assess obstructive sleep apnea severity, is predictive of all-cause and CVD mortality, and may be a viable alternative to the AHI.

The interplay between X-chromosome functional dosage and circadian regulation in females.

PURPOSE: Biological factors and mechanisms that drive higher prevalence of insomnia in females are poorly understood. This study focused on the neurological consequences of X-chromosome functional imbalances between sexes. METHODS: Benefited from publicly available large-scale genetic, transcriptional and epigenomic data, we curated and contrasted different gene lists: (1) X-liked genes, including assignments for X-chromosome inactivation patterns and disease associations; (2) sleep-associated genes; (3) gene expression markers for the suprachiasmatic nucleus. RESULTS: We show that X-linked markers for the suprachiasmatic nucleus are significantly enriched for clinically relevant genes in the context of rare genetic syndromes and brain waves modulation. CONCLUSION: Considering female-specific patterns on brain transcriptional programs becomes essential when designing health care strategies for mental and sleep illnesses with sex bias in prevalence.

The relationship between irritable bowel syndrome, the gut microbiome, and obstructive sleep apnea: the role of the gut-brain axis.

Sleep disruption, especially that resulting from obstructive sleep apnea (OSA) - a widely prevalent sleep disorder - can lead to important systemic repercussions. We raise a subject of current interest, namely the possible relationship between sleep in general, OSA, and irritable bowel syndrome (IBS), an intestinal disease that can be made worse by stressful events. The intermittent hypoxia caused by OSA can induce alterations in the gut microbiota, which can lead to the dysregulation of the gut-brain axis and the worsening of IBS. This may be considered to be a circular relationship, with OSA playing a crucial role in the worsening of bowel symptoms, which in turn have a negative effect on sleep. Thus, based on previous evidence, we suggest that improving sleep quality could be a key to disrupting this relationship of IBS aggravation and OSA.

How do phases of the menstrual cycle affect sleep? A polysomnographic study of the EPISONO database.

PURPOSE: Our study aimed to evaluate the impact of the menstrual cycle stages, especially menses, on sleep, inflammatory mediators, fatigue, anxiety, depression, and quality of life. METHODS: We used data from the EPISONO study cohort, selecting 96 women who had undergone one-night polysomnography. The women were distributed in three groups according to the time point of the menstrual cycle on the polysomnography night: menses, mid/late follicular phase, and luteal phase. The volunteers completed questionnaires related to sleep quality, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. Blood samples were collected to analyze interleukin 6, tumor necrosis factor-alpha, and C-reactive protein. RESULTS: Sleep efficiency was statistically higher in women in the mid/late follicular group (89.9% ± 9.6) compared to menstrual (83.0% ± 10.8) and luteal (83.7% ± 12.7) groups. The mid/late follicular group presented a statistically significant reduction in sleep onset latency (7.1 ± 7.1 min) compared to the menstrual (22.3 ± 32.4 min) and luteal groups (15.9 ± 14.7 min). No statistical differences among the three groups were observed in other polysomnographic parameters, inflammatory mediators, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. CONCLUSIONS: Our findings demonstrate that the mid/late follicular phase might be beneficial for women's sleep, although there were no statistically changes in inflammatory mediators among the groups.

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.

Insomnia Symptoms and Menstrual Health: Is There a Link in Women During Reproductive Phase of Life?

OBJECTIVES: To investigate the association between insomnia severity symptoms and menstrual health, fatigue and anxiety symptoms in women at reproductive age. METHOD: We used data from EPISONO (2007), an epidemiological study from the city of São Paulo, Brazil. Women completed the Insomnia Severity Index (ISI), the Chalder Fatigue Scale (CFS), and the Beck Anxiety Inventory (BAI) to obtain information about insomnia, fatigue, and anxiety symptoms. For menstrual health, we collected information using our Institutional Women's Questionnaire about menstrual flow and duration, the presence of pain during menstruation and menstrual cycle regularity. The statistical analysis was performed using ordinal logistic regression, considering p < .05. RESULTS: Of the 1,042 participants, only 282 women met the inclusion criteria to participate in this study. The mean age was 34.4 years (SD ± 8.36), and the body mass index (BMI) was 25.7 (SD ± 5.39). According to the model, a 1-unit higher CFS score increased the odds of having more insomnia symptoms in the ISI (OR = 1.170; 95% CI=[1.073; 1.279]; p < .001). In the same way, a 1-unit higher BAI score increased the chance of presenting insomnia symptoms, according to the ISI (OR = 1.072; 95% CI=[1.042; 1.104]; p < .001). The menstrual variables did not represent statistical significance in the model. CONCLUSIONS: Fatigue and anxiety symptoms were associated with insomnia symptoms; however, no association was observed between menstrual health and insomnia. The need to examine sleep when there are sleep complaints is essential to provide an accurate diagnosis that facilitates appropriate treatment and to provide better sleep quality for women.

Homocysteine as a predictor of apnea-hypopnea index in obstructive sleep apnea: a longitudinal epidemiological study (EPISONO).

BACKGROUND: Obstructive sleep apnea (OSA) affects nearly 1 billion people globally, and has established links with cardiovascular and neurocognitive complications. Although it has some limitations, the apnea-hypopnea index (AHI) is commonly used to gauge OSA severity and therapeutic response. Homocysteine (Hcy) metabolism, when impaired, can elicit cellular senescence mechanisms that may be shared with OSA. Hence, our objective was to explore the role of Hcy concentrations both as a predictor of AHI values and as a potential risk factor for OSA. METHODS: Involving 1042 volunteers aged 20 to 80 years, the initial study (2007) included polysomnographic evaluations, questionnaires on sleep and general health, as well as biochemical analyses. After an 8-year interval, 715 participants from the initial study were invited for a follow-up assessment in 2015. RESULTS: Our findings showed that Hcy was a predictor for an increased AHI, and AHI increased over time. Individuals with plasma Hcy concentrations ≥ 15 µmol/L experienced an average AHI increase of 7.43 events/hour ([beta coefficient] ß = 7.43; 95%CI 2.73 to 12.13) over time, compared to those with plasma concentrations < 10 µmol/L. A similar trend was apparent in those with plasma Hcy concentrations between 10 ≥ and < 15 µmol/L, who had an AHI increase with an average beta coefficient of 3.20 events/hour (95%CI 1.01 to 5.39) compared to those with plasma Hcy concentrations < 10 µmol/L. CONCLUSIONS: In summary, our study suggests that increased plasma Hcy concentrations could be considered a risk factor for the development of OSA. These findings highlight that elevated plasma Hcy concentrations can predict the severity of OSA, underscoring their correlation with the AHI.

Changes in behavioral and cognitive abilities after rapid maxillary expansion in children affected by persistent snoring after long-term adenotonsillectomy: A noncontrolled study.

INTRODUCTION: The objective of this study was to verify changes in behavioral abilities and cognitive functions after rapid maxillary expansion (RME) in children with refractory sleep-disordered breathing (SDB) in the long term after adenotonsillectomy. METHODS: A prospective clinical trial study using RME therapy was conducted. Participant inclusion criteria were children who had adenotonsillectomy with maxillary transverse deficiency and persistent SDB (obstructive apnea-hypopnea index ≥1). The study included 24 children aged 5-12 years, and of these 24 children, 13 had primary snoring and 11 had obstructive sleep apnea. The patients underwent laryngeal nasofibroscopy and a complete polysomnography. In addition, patients completed the Obstructive Pediatric Sleep Questionnaire and Obstructive Sleep Apnea 18-Item Quality-of-Life Questionnaire. Behavioral and neurocognitive tests were also completed before and after RME. RESULTS: The Obstructive Pediatric Sleep Questionnaire and Obstructive Sleep Apnea 18-Item Quality-of-Life scores showed a statistically significant decrease in both groups (P <0.001) after RME. The results showed that neurocognitive and behavioral parameters (Child Behavior Checklist scale) were similar in primary snoring and obstructive sleep apnea (OSA) groups before RME. In the OSA group, the mean scores of the "Somatic" and "Aggressiveness" domains decreased significantly (P <0.05). The cognitive functions did not register significant differences pre- and post-RME in any of the cognitive functions, except for visuospatial function in the OSA group. CONCLUSIONS: The noncontrolled design was a major limitation of our study. The need for treatment for SDB should consider the association of symptoms and behavioral disturbances with the child's obstructive apnea-hypopnea index. RME might prove to be an alternative treatment for children with SDB refractory to adenotonsillectomy, improving quality of life and behavioral aspects. However, a larger sample size with a control group is needed to substantiate these claims.

Genetic basis of sleep phenotypes and rare neurodevelopmental syndromes reveal shared molecular pathways.

Sleep-related phenotypes have been frequently reported in early on-set epileptic encephalopathies and in developmental delay syndromes, in particular in syndromes related to autism spectrum disorder. Yet the convergent pathogenetic mechanisms between these comorbidities are largely unknown. We first performed a gene enrichment study that identified shared risk genes among rare epileptic encephalopathies/neurodevelopmental disorders, rare developmental delay genetic syndromes and sleep disturbances. We then determined cellular and molecular pathways enriched among genes shared between sleep phenotypes and those two early onset mental illnesses, aiming to identify genetic disparities and commonalities among these phenotypic groups. The sleep gene set was observed as significantly overlapped with the two gene lists associated to rare genetic syndromes (i.e., epileptic encephalopathies/neurodevelopmental disorders and developmental delay gene sets), suggesting shared genetic contribution. Similarities across significantly enriched pathways between the two intersect lists comprehended mostly synapse-related pathways, such as retrograde endocannabinoid signaling, serotonergic, and GABAergic synapse. Network analysis indicates epileptic encephalopathies/neurodevelopmental disorders versus sleep-specific clusters and developmental delay versus sleep-specific clusters related to synaptic and transcriptional regulation, respectively. Longstanding functional patterns previously described in epileptic encephalopathies and neurodevelopmental disorders genetic architecture were recaptured after dissecting the overlap between the genes associated to those developmental phenotypes and sleep disturbances, suggesting that during neurodevelopment different molecular and functional mechanisms are related to alterations on circadian rhythm. The overlapping gene set and biological pathways highlighted by this study may serve as a primer for new functional investigations of shared molecular mechanisms between sleep disturbances and rare developmental syndromes.

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.

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.

Influence of social jetlag on daytime sleepiness in obstructive sleep apnea.

Social jetlag is the discrepancy between socially determined sleep timing on workdays and biologically determined sleep timing on days free of social obligation. Poor circadian timing of sleep may worsen sleep quality and increase daytime sleepiness in obstructive sleep apnea (OSA). We analysed de-identified data from 2,061 participants (75.2% male, mean [SD] age 48.6 [13.4] years) who completed Sleep Apnea Global Interdisciplinary Consortium (SAGIC) research questionnaires and underwent polysomnography at 11 international sleep clinic sites. Social jetlag was calculated as the absolute difference in the midpoints of sleep between weekdays and weekends. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Linear regression analyses were performed to estimate the association between social jetlag and daytime sleepiness, with consideration of age, sex, body mass index, ethnicity, insomnia, alcohol consumption, and habitual sleep duration as confounders. Of the participants, 61.5% had <1 h of social jetlag, 27.5% had 1 to <2 h, and 11.1% had ≥2 h. Compared to those with <1 h of social jetlag, those with ≥2 h of social jetlag had 2.07 points higher ESS (95% confidence interval [CI] 0.77-3.38, p = 0.002), and those with 1 to <2 h of social jetlag had 0.80 points higher ESS (95% CI 0.04-1.55, p = 0.04) after adjustment for potential confounding. Interaction with OSA severity was observed; social jetlag appeared to have the greatest effect on daytime sleepiness in mild OSA. As social jetlag exacerbates daytime sleepiness in OSA, improving sleep timing may be a simple but novel therapeutic target for reducing the impact of OSA.

Sleep characteristics and inflammatory markers in women with post-traumatic stress disorder.

INTRODUCTION: Sexual violence is one of the most severe traumatic events. It is associated with a higher risk for post-traumatic stress disorder (PTSD) development. Sleep disturbances such as insomnia are frequently reported by PTSD patients and play a key role in the development and course of the disorder. Sleep disturbances are associated with higher levels of pro-inflammatory cytokines emphasizing the importance of sleep studies in individuals with PTSD. OBJECTIVES: To investigate the association between subjective and objective sleep measurements and PTSD symptoms with inflammatory markers in women with PTSD following sexual assault. METHODS: In this longitudinal study fifty-seven women with PTSD were evaluated for sleep measurements and inflammatory markers. Participants completed the Clinician-Administered PTSD Scale, the Beck Depression Inventory, the Pittsburgh Sleep Quality Index (PSQI), and the Insomnia Severity Index. In addition, patients underwent full in-lab polysomnography and serum levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) measurement. All assessments were performed at baseline and after one year. Patients received pharmacological and/or psychological interventions between baseline and one-year follow-up. RESULTS: Despite improving PTSD symptoms severity and sleep quality (expressed in PSQI), we found an increase in the inflammatory markers IL-1ß, TNF-α, IL-6 and CRP after one year of follow-up. These findings suggest that neurobiological processes may advance independently of PTSD symptoms. We found a significant increase in the levels of IL-1ß and TNF-α associated with decreased slow-wave sleep (p = 0.019 and p = 0.018 respectively), IL-6 associated with arousal index (p = 0.024), and CRP associated with insomnia severity (p = 0.012), and sleep duration longer than 6 h per night (p < 0.001). CONCLUSIONS: Sleep impairments in PTSD may be associated with a gradual and persistent alteration in the immune system, resulting in a progressive inflammatory process. Our results suggest that sleep mechanisms are involved in this incident inflammatory process in young women with PTSD.

Do nocturnal asthma attacks influence sleep parameters and inflammatory markers? A cross-sectional population-based study.

PURPOSE: To evaluate the effects of nocturnal asthma on sleep parameters and inflammatory markers according to the severity of the condition in participants in the São Paulo Epidemiologic Sleep Study (EPISONO). METHODS: Data from the 2007 and 2018 editions of the EPISONO study were utilized. Subjects completed validated sleep and respiratory questionnaires, underwent nocturnal polysomnography and spirometry tests, and provided blood samples for the assessment of inflammatory parameters. RESULTS: Of 72 participants (67% women), 53% (n = 38) had intermittent nocturnal asthma symptoms and 47% (n = 34) had persistent asthma (mild, moderate, and severe). Individuals with persistent nocturnal symptoms had a higher body mass index (BMI), were more likely to have respiratory symptoms, and had worse lung function, a higher apnea-hypopnea index (AHI), and higher desaturation index than individuals with intermittent nocturnal symptoms. Positive associations were identified between nocturnal asthma and obstructive sleep apnea (OSA). A higher frequency of OSA was observed in participants with persistent asthma and participants with OSA were more likely to have persistent than intermittent asthma. However, there were no significant differences between the immunological parameters of those with intermittent or persistent asthma. CONCLUSIONS: This study highlights the relevance of nocturnal symptoms as a valuable indicator of asthma severity. The findings also add to the existing body of evidence linking nocturnal asthma and OSA.

The effects of rapid maxillary expansion on persistent pediatric snoring post-tonsillectomy.

PURPOSE: To investigate the short-term effects of rapid maxillary expansion (RME) on the quality of life of children who had persistent snoring post-adenotonsillectomy (AT). METHODS: The study included children with maxillary constriction aged 5 to 12 years, two or more years after AT whose parents/guardians reported that they still snored ≥ 5 nights per week. We enrolled children with sleep-disordered breathing, including children with primary snoring and children with obstructive sleep apnea (OSA). All patients underwent laryngeal nasofibroscopy and complete polysomnography. Quality of Life (QOL) Questionnaire (OSA-18), the Pediatric Sleep Questionnaire (PSQ), Conners Abbreviated Scale (CAS), and the Epworth Sleepiness Scale (ESS) were administered before and after RME. RESULTS: Of 24 children enrolled, 13 had primary snoring and 11 had OSA. Overall OSA-18 scores were reduced in both groups (intragroup difference, p < 0.001). The PSQ total score, CAS, and ESS were significantly reduced in both groups (p < 0.001) In the evaluation of snoring, there was a reduction due to the treatment effect in both groups (p < 0.001). Daytime sleepiness and attention deficit hyperactivity disorders were also positively affected in both groups. CONCLUSIONS: Our study demonstrated the potential benefit of RME in treating children with persistent snoring and transverse maxillary deficiency (TMD). RME can improve snoring and the QOL of children with refractory SDB after AT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: RBR-463byn.

Effect of CPAP vs. mandibular advancement device for excessive daytime sleepiness, fatigue, mood, sustained attention, and quality of life in patients with mild OSA.

OBJECTIVE: This study's objective was to compare the best long-term treatment, mandibular advancement device (MAD) or continuous positive airway pressure (CPAP), for patients with mild obstructive sleep apnea (OSA) in improving excessive daytime sleepiness, fatigue, mood, sustained attention, and quality of life. METHODS: This study was a single-blind, parallel, randomized clinical trial with controls. The sample was composed of individuals between 18 and 65 years of age with a body mass index of < 35 kg/m2 and apnea/hypopnea index above five and less than 15. Participants were submitted to physical examination, polysomnography, and the following questionnaires: Pittsburgh Sleep Quality Index, Berlin Questionnaire, Epworth Sleepiness Scale, Stanford Sleepiness Scale, Karolinska Sleepiness Scale, Modified Fatigue Impact Scale, Functional Outcomes of Sleep Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory. They were also presented with the following tests: maintenance of wakefulness test and psychomotor vigilance task. RESULTS: Of 79 patients, 25 were in the MAD group, 31 in the CPAP group, and 23 in the control group. Polysomnographic parameters were best normalized with CPAP compared with MAD. Fatigue was improved in the MAD and CPAP groups, with no difference between these treatments. Quality of life was also improved with both treatments, but CPAP was superior to MAD. Daytime sleepiness, mood, and sustained attention showed no difference with the interventions. Greater adherence was obtained with MAD patients than with CPAP measured by hours of use. CONCLUSIONS: Treatment with CPAP was better at normalizing polysomnographic parameters and improving quality of life in patients with mild OSA. Both treatments improved fatigue with no difference between the two treatments. Neither treatment improved daytime sleepiness, mood or sustained attention. CLINICAL TRIALS DATABASE: NTC01461486.