Exploring the Link between Premature Ovarian Insufficiency, Insomnia and Circadian Pathways.

OBJECTIVE: To establish an interaction network for genes related to premature ovarian insufficiency (POI) and insomnia, and to identify biological processes that connect POI to the physiological clock. METHODS: Previously reported lists of genes associated to POI and insomnia were contrasted and their intersection was used as input on protein-protein interaction analyses. POI-associated genes were contrasted with gene expression markers for neural circadian control and enriched pathways among their shared content were dissected. RESULTS: The functional network generated from the intersection between POI and insomnia gene lists pointed to the central nervous system as the most relevant cellular context for this connection. After identifying POI-associated genes that play a role in neural circadian patterns, we observed the disruption of pathways related to the hypothalamic-pituitary-gonadal axis as the major genetic link between ovarian function and circadian neural circuits. CONCLUSIONS: These findings highlight neurological mechanisms that support the POI-insomnia interplay.

The influence of phototherapy on circadian melatonin and sleep regulation and potential benefits of these pathways in the management of vitiligo: a narrative review : Vitiligo, phototherapy, sleep and melatonin.

Ultraviolet B narrow band (UVB-NB) phototherapy is the gold standard treatment for vitiligo, primarily due to its immunomodulatory effects. Additionally, it may influence circadian melatonin balance, that may indirectly induce sleep regulation, which in turn could potentially contribute to vitiligo improvement. The association between melatonin, vitiligo and phototherapy has been little investigated. The aim of this study was to evaluate the current evidence regarding the effects of circadian melatonin regulation and sleep, particularly during vitiligo treatment with phototherapy. We undertook a narrative review to synthetize the evidence on this association through the MEDLINE/PubMed database, using combined search terms: melatonin, vitiligo, phototherapy, and circadian rhythm (sleep). A total of 56 articles were included. There are few studies on this relationship, and conflicting findings. Some studies have suggested that UV exposure and phototherapy might benefit vitiligo by stimulating melanocytes, which have melatonin receptors, and this could potentially synchronize the circadian regulation of melatonin. This improved melatonin balance could result in better sleep quality further enhancing the antiinflammatory properties of melatonin and contributing to vitiligo improvement. Less is known about the possible effects of the use of topical melatonin, with or without phototherapy, to treat vitiligo lesions. In conclusion, there is some evidence that circadian melatonin regulation plays an important role in the course of vitiligo, both through sleep regulation and its anti-inflammatory properties. The evidence suggests that the systemic and physiological properties of melatonin, especially its circadian behavior regulated by phototherapy, may be more effective in respect of vitiligo improvement than the use of topical melatonin. However, the effects of the oral intake of melatonin are less clear. Phototherapy, as a potential modulator of circadian melatonin rhythm, that influences sleep and clinical improvement of vitiligo, needs further examination, as does the use of melatonin as an adjuvant treatment to UVB phototherapy in vitiligo.

Associations between real-life light exposure patterns and sleep behaviour in adolescents.

One of the most striking changes in the regulation of sleep-wake behaviour during adolescence is circadian phase delay. Light exposure synchronises circadian rhythms, impacting sleep regulation, however, the influence of real-life light exposure on sleep variations remains less clear. We aimed to describe the sleep and light exposure patterns of high school students with comparable schedules and socio-economic backgrounds, and to evaluate whether there was any association between them, considering chronotype. We analysed five school days and two free days of actigraphy records, from 35 adolescents (24 female, mean age: 16.23 ± 0.60). The sample was described using the Sleep Regularity Index (SRI), chronotype (actigraphy MSFsc), and self-reported diurnal preference (Morning/Evening Scale). Regression models were constructed to assess the impact of light exposure (daytime and nighttime) on subsequent sleep episodes; and to confirm whether the associations could be an indirect consequence of chronotype. Despite following similar routines, the SRI varied considerably (48.25 to 88.28). There was compatibility between the actigraphy proxy for chronotype and the self-reported diurnal preference, extracted using the circadian rhythm scale for adolescents. Less light exposure during the day was associated with later sleep onset and shorter sleep duration. An increase of 100 lux in average daytime light exposure advance of 8.08 minutes in sleep onset and 7.16 min in sleep offset. When the regressions were controlled for chronotype, these associations persisted. These findings facilitate discussions regarding the behavioural aspect of the impact of real-life light exposure on sleep and its potential as a target for interventions aiming to enhance adolescents' sleep quality.

Artificial Intelligence, the Production of Scientific Texts, and the Implications for Sleep Science: Exploring Emerging Paradigms and Perspectives.

The emergence of artificial intelligence (AI) has revolutionized many fields, including natural language processing, and marks a potential paradigm shift in the way we evaluate knowledge. One significant innovation in this area is ChatGPT, a large language model based on the GPT-3.5 architecture created by OpenAI, with one of its main aims being to aid in general text writing, including scientific texts. Here, we highlight the challenges and opportunities related to using generative AI and discuss both the benefits of its use, such as saving time by streamlining the writing process and reducing the amount of time spent on mundane tasks, and the potential drawbacks, including concerns regarding the accuracy and reliability of the information generated and its ethical use. In respect of both education and the writing of scientific texts, clear rules and objectives and institutional principles must be established for the use of AI. We also consider the positive and negative effects of the use of AI technologies on interpersonal interactions and behavior, and, as sleep scientists, its potential impacts on sleep. Striking a balance between the benefits and potential drawbacks of integrating AI into society demands ongoing research by experts, the wide dissemination of the scientific results, as well as continued public discourse on the subject.

Sleep Debt and Insulin Resistance: What's Worse, Sleep Deprivation or Sleep Restriction?

Objective To evaluate which condition of sleep debt has a greater negative impact on insulin resistance: sleep deprivation for 24 hours or 4 hours of sleep restriction for 4 nights. Materials and Methods In total, 28 healthy male subjects aged 18 to 40 years were recruited and randomly allocated to two groups: sleep deprivation (SD) and sleep restriction (SR). Each group underwent two conditions: regular sleep (11 pm to 7 am ) and total sleep deprivation for 24 hours (SD); regular sleep (11 pm to 7 am ) and 4 nights of sleep restriction (SR) (1 am to 5 am ). The oral glucose tolerance test (OGTT) was performed, and baseline glucose, insulin, free fatty acids (FFAs), and cortisol were measured. In addition, the area under the curve (AUC) for glucose and insulin, the homeostasis model assessment of insulin resistance (HOMA-IR), and the Matsuda Index (Insulin Sensitivity Index, ISI) were calculated. Results Glucose and insulin had a similar pattern between groups, except at the baseline, when insulin was higher in the sleep debt condition of the SR when compared with the SD ( p < 0.01). In the comparison between regular sleep and sleep debt, the SD had a higher insulin AUC ( p < 0.01) and FFAs ( p = 0.03) after sleep deprivation, and insulin and the insulin AUC increased ( p < 0.01 for both), while the ISI decreased ( p = 0.02) after sleep restriction in the SR. In baseline parameters covariate by the condition of regular sleep, insulin ( p = 0.02) and the HOMA-IR ( p < 0.01) were higher, and cortisol ( p = 0.04) was lower after sleep restriction when compared with sleep deprivation. Conclusion Sleep restriction for 4 consecutive nights is more detrimental to energy metabolism because of the higher insulin values and insulin resistance compared with an acute period of sleep deprivation of 24 hours.

Unlocking the role of Galectin-3: Implications for sleep disorders and health.

Galectin-3 is a member of the lectin family, and is an intriguing protein that is found in diverse tissues across the body. It is known for its multifaceted involvement in various physiological functions, including tissue repair, immune function and neuroinflammation in the central nervous system. It also serves as a paracrine signal, promoting the growth of certain cells and contributing to fibrosis, while higher levels of Galectin-3 in the bloodstream correlate with an increased risk of mortality and cardiovascular disease-related outcomes in the general population. Recent scientific studies have identified a potential link between Galectin-3 and sleep disorders. However, the precise mechanisms through which galectin-3 influences sleep disorders remain an active area of investigation. Although initial studies suggest a potential association between Galectin-3 and sleep disruptions, including conditions, such as insomnia, insufficient sleep time, and obstructive sleep apnea, further research is required to establish a more definitive relationship. This review explores recent findings regarding the potential connection between Galectin-3 and sleep patterns, and offers insights into the complex interplay between this protein and sleep. These discoveries present promising prospects for the development of innovative therapeutic approaches aimed at sleep disorder management, using Galectin-3 as a potential target for interventions or as a biomarker for sleep health.

Cellular senescence and sleep in childhood and adolescence: A scoping review focusing on sleep-disordered breathing.

BACKGROUND: Sleep is a fundamental and complex physiological process whose duration decreases and characteristics change with age. Around 50 % of children will experience sleep disturbances at some point in their early life. Sleep disturbances can result in a number of deleterious consequences, including alterations in the levels of cellular senescence (CS) markers. CS is a complex process essential for homeostasis characterized by the irreversible loss of cell proliferation capacity; however, the accumulation of senescent cells can lead to age-related diseases. OBJECTIVE: In this review, our objective was to gather information about the relationship between sleep duration, sleep-disordered breathing (SDB) and cellular senescence markers, namely: oxidative stress, inflammation, insulin-like growth factor 1 (IGF-1), and growth hormone (GH) in newborns, children, and teenagers. METHODS: To achieve this, we searched six databases: MEDLINE, Scopus, LILACS, Web of Science, Embase, and SciELO, and identified 20 articles that met our inclusion criteria. RESULTS: Our results show that better sleep quality and duration and, both the surgical and non-surgical treatment of sleep disorders are associated with a reduction in oxidative stress, inflammation, and telomeric attrition levels. Furthermore, our results also show that surgical treatment for SDB significantly reduced the levels of cellular senescence markers. Further studies need to be conducted in this area, particularly longitudinal studies, for a greater understanding of the mechanisms involved in the relationship between sleep and senescence. CONCLUSION: Better sleep quality and duration were associated with less oxidative stress, inflammation, and telomeric attrition and a higher level of IGF-1 in children and teenagers.

Altered sleep and diurnal consequences in women with dysmenorrhea: study from the EPISONO database.

PURPOSE: Our study aimed to identify alterations in sleep, inflammatory mediators, fatigue and quality of life in women with dysmenorrhea and compare them to women without dysmenorrhea. METHODS: The sample comprised 328 women from a Brazilian cross-sectional sleep study, EPISONO (2007), who had undergone 1-night polysomnography (PSG) type I and completed questionnaires related to sleep quality, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. Blood samples were used to assess levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). The 2 groups were distributed based on the presence or absence of dysmenorrhea symptoms. RESULTS: Sleep efficiency was significantly lower in the group of women with dysmenorrhea (82.5% ± 13.8) compared to the non-dysmenorrhea group (86.2% ± 10.9). Dysmenorrhea was associated with significantly higher scores of fatigue and worse scores in the physical quality of life. No statistical differences were detected in inflammatory markers between the 2 groups. DISCUSSION: Fatigue and physical quality of life were presented in women with dysmenorrhea, as was reduced sleep efficiency, although no alteration on inflammatory markers were observed. CONCLUSION: These findings show that dysmenorrhea can have a deleterious effect on women's sleep, with repercussions on daily routines and quality of life.

Sleep disturbances associated with DEAF1 pathogenic variants.

Neurodevelopmental disorders and sleep disturbances share genetic risk factors. DEAF1 genetic variants are associated with rare syndromes in which sleep disturbances are commonly reported, yet the specific sleep disorders in these patients, and the molecular mechanisms underlying this association, are unknown. We aimed to pinpoint specific biological processes that may be disrupted by pathogenic variants in this gene, comparing a list of DEAF1 regulatory target genes with a list of insomnia-associated genes, and using the intersect gene list as the input for pathway enrichment analysis. Thirty-nine DEAF1 regulatory targets were also identified as insomnia-associated genes, and the intersecting gene list was found to be strongly associated with immune processes, ubiquitin-mediated proteolysis pathways and regulation of the cell cycle. This preliminary study highlights pathways that may be disrupted by DEAF1 pathogenic mutations and might be putative factors underlying the manifestation of insomnia in patients harboring such variants.

Subjective sleep assessment in individuals with SYNGAP1-associated syndrome.

STUDY OBJECTIVES: Sleep disturbances are common in neurodevelopmental disorders (NDDs), affecting patients and caregivers' quality of life. SYNGAP1-associated syndrome, a rare NDD, is marked by intellectual disability, developmental delay, epilepsy, and sleep issues. However, research on sleep quality in these individuals is limited. This study aimed to evaluate genetic variants, epilepsy, and sleep patterns in SYNGAP1-associated syndrome patients and their caregivers. METHODS: An online survey was applied to 11 caregivers of individuals diagnosed with SYNGAP1-associated syndrome. Specific clinical inquiries were included, addressing childbirth, previous surgeries, and medication use. Inquiries about epilepsy included type of epilepsy, type and frequency of seizures, anti-seizure medications, and complementary non-pharmacological treatments. Children's Sleep Habits Questionnaire (CSHQ) was applied to assess the patients' sleep profile. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of caregivers. RESULTS: Genetic analysis showed heterozygous mutations in SYNGAP1, often leading to loss of function. Epilepsy was present in 82% of participants, with 77.8% having drug-resistant seizures. Using the Children's Sleep Habits Questionnaire (CSHQ), 81.8% of patients exhibited poor sleep habits, including bedtime resistance, anxiety, night awakenings, parasomnias, and daytime sleepiness. Caregivers also reported poor sleep quality according to the Pittsburgh Sleep Quality Index (PSQI). CONCLUSIONS: This study highlights the high prevalence of epilepsy and sleep problems in SYNGAP1-associated syndrome, impacting both patients and caregivers. Further research is crucial to understand the syndrome's effects on sleep disturbances, emphasizing the need for targeted interventions to improve sleep quality in individuals with rare genetic syndromes and their caregivers.

Sleep is associated with telomere shortening: A population-based longitudinal study.

As the chronological age increases, there is a decrease in the telomere length (TL). Associations between TL and age-related diseases have been described. Since the major pathophysiological factors related to inadequate sleep (including sleep complaints and sleep disorders) contribute to the exacerbation of inflammation and oxidative stress, an association of sleep and TL has been proposed. The aim of this study was to evaluate the association between sleep-related variables with TL in a longitudinal framework. We used data derived from the EPISONO cohort, which was followed over 8 years. All individuals answered sleep-related questionnaires, underwent a full-night polysomnography (PSG), and had their blood collected for DNA extraction. The TL was measured through a quantitative real time polymerase chain reaction. Age, sex, body mass index (BMI), smoking, physical activity status, and the 10 principal components (ancestry estimate) were considered covariables. Of the 1042 individuals in the EPISONO cohort, 68.3% agreed to participate in the follow-up study (n = 712). Baseline SpO2 (ß = 0.008, p = 0.007), medium SpO2 (ß = 0.013, p = 0.013), and total sleep time <90% (ß = -0.122, p = 0.012) had an effect on TL from the follow-up. The 8 year TL attrition was inversely associated with total sleep time, sleep efficiency, sleep architecture variables, wake after sleep onset, arousal index, oxygen-related variables baseline, and the presence of obstructive sleep apnea (OSA). We conclude that individuals with worse sleep quality, alterations in sleep architecture, and OSA had greater TL attrition over the 8 years. Using a longitudinal approach, these findings confirm previous cross-sectional evidence linking sleep with accelerated biological ageing.

Amyloid profile is associated with sleep quality in preclinical but not in prodromal Alzheimer's disease older adults.

BACKGROUND: Few studies have assessed whether neuropathological markers of AD in the preclinical and prodromal stages are associated with polysomnographic changes and obstructive sleep apnea (OSA). METHODS: This was a cross-sectional, case-control study of older adults (≥60 years) without relevant clinical and psychiatric comorbidities selected randomly from a cohort of individuals without dementia in a tertiary university hospital in São Paulo, Brazil. They underwent neuropsychological evaluation for clinical diagnosis and were allocated into two samples: cognitively unimpaired (CU) and mild cognitive impairment (MCI). Also, they underwent PET-PiB to determine the amyloid profile and all-night in-lab polysomnography. For each sample, we compared polysomnographic parameters according to the amyloid profile (A+ vs A-). RESULTS: We allocated 67 participants (mean age 73 years, SD 10,1), 70 % females, 14 ± 5 years of education, into two samples: CU (n = 28, 42.4 %) and MCI (n = 39, 57.6 %). In the CU sample, the group A+ (n = 9) showed worse sleep parameters than A- (n = 19) (lower total sleep time (p = 0.007), and sleep efficiency (p = 0.005); higher sleep onset latency (p = 0.025), wake time after sleep onset (p = 0.011), and arousal index (AI) (p = 0.007)), and changes in sleep structure: higher %N1 (p = 0.005), and lower %REM (p = 0.006). In the MCI sample, MCI A-had higher AI (p = 0.013), respiratory disturbance index (p = 0.025, controlled for age), and higher rates of severe OSA than A+. DISCUSSION: The amyloid profile was associated with polysomnographic markers of worse sleep quality in individuals with preclinical AD but not with prodromal AD, probably due to the higher frequencies of severe OSA.

Erectile dysfunction and sleep related bruxism: An exploratory review of an improbable association.

The World Health Organization recognizes sexual health as not merely the absence of disease, but a state of physical, mental, and social well-being in relation to one's sexuality. Achieving sexual satisfaction is pivotal for many individuals, as it significantly contributes to their quality of life. Among various sexual disorders, erectile dysfunction (ED) is notably prevalent, affecting an estimated 10-20 million men in the United States alone. This condition impacts not just the person experiencing it but also significantly influences their intimate connections with partners. Although the causes of ED are multifactorial, recent research highlights a compelling association between sleep disorders, such as sleep deprivation, obstructive sleep apnea (OSA), and insomnia, and the incidence of ED. Furthermore, engaging in night work has been observed to exacerbate the risk of developing ED. One common sleep disorder, sleep related bruxism (SRB), despite its prevalence, has not generally been associated with ED. However, there is some interesting evidence hinting at a potential relationship, including a few studies reporting a high prevalence of ED in individuals with SRB. This review delves into the epidemiological, etiological, and mechanistic links between ED and SRB, aiming to uncover potential intersections between these two conditions. These insights could pave the way for innovative research avenues, possibly exploring treatments like vasodilation medication, that might concurrently address both ED and SRB.

Kinesin binding as a shared pathway underlying the genetic basis of male factor infertility and insomnia.

OBJECTIVE: To study whether male factor infertility and insomnia share genetic risk variants and identify any molecular, cellular, and biologic interactions between these traits. DESIGN: The in silico study was performed. Two lists of genetic variants were manually curated through a literature review, one of those associated with male factor infertility and the other with insomnia. Genes were assigned to these variants to compose male factor infertility-associated (454 genes) and insomnia-associated (921 genes) gene lists. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Enrichment of biologic pathways and protein-protein interaction analysis. RESULT(S): Twenty-eight genes were common to both lists, representing a greater overlap than would be expected by chance. In the 28 genes contained in the intersection list, there was a significant enrichment of pathways related to kinesin binding. A protein-protein interaction analysis using the intersection list as input retrieved 25 nodes and indicated that two of them were kinesin-related proteins (PLEKHM2 and KCL1). CONCLUSION(S): The shared male factor infertility and insomnia genes, and the biologic pathways highlighted in this study, suggest that further functional investigations into the interplay between fertility and sleep are warranted.

The Impact of Sleep: From Ancient Rituals to Modern Challenges.

Although sleep is crucial for mental and physical health, insufficient sleep is a growing problem in our modern society. In general, adults need approximately eight hours of sleep per night, but this is often unfeasible nowadays. This sleep restriction has been observed, and it has worsened, throughout the past two centuries; therefore, it is more attributed to socioeconomic changes than to biological adaptations. The most important factors to contribute to this sleep restriction were the popularization of artificial light and industrialization. The present manuscript briefly overviews, from a socioanthropological perspective, the reasons why sleep has been impacted, disclosing its effects on individuals and on society.

Sleep staging algorithm based on smartwatch sensors for healthy and sleep apnea populations.

OBJECTIVE: Sleep stages can provide valuable insights into an individual's sleep quality. By leveraging movement and heart rate data collected by modern smartwatches, it is possible to enable the sleep staging feature and enhance users' understanding about their sleep and health conditions. METHOD: In this paper, we present and validate a recurrent neural network based model with 23 input features extracted from accelerometer and photoplethysmography sensors data for both healthy and sleep apnea populations. We designed a lightweight and fast solution to enable the prediction of sleep stages for each 30-s epoch. This solution was developed using a large dataset of 1522 night recordings collected from a highly heterogeneous population and different versions of Samsung smartwatch. RESULTS: In the classification of four sleep stages (wake, light, deep, and rapid eye movements sleep), the proposed solution achieved 71.6 % of balanced accuracy and a Cohen's kappa of 0.56 in a test set with 586 recordings. CONCLUSION: The results presented in this paper validate our proposal as a competitive wearable solution for sleep staging. Additionally, the use of a large and diverse data set contributes to the robustness of our solution, and corroborates the validation of algorithm's performance. Some additional analysis performed for healthy and sleep apnea population demonstrated that algorithm's performance has low correlation with demographic variables.

Bimodal diurnal preference in undergraduate students is associated with negative health and sleep outcomes.

The bimodal preference is a fourth diurnal preference proposed by re-scoring the Morningness-Eveningness Questionnaire. The present work aimed to describe the prevalence of the bimodal preference in a sample of undergraduate students and to characterize the bimodal type in terms of their health and sleep-related outcomes. A web-based cross-sectional study conducted between September 2018 and March 2021 (convenience sampling method). The sample was composed of undergraduate students who completed an electronic form that included the Morningness and Eveningness Questionnaire, the Pittsburgh Sleep Quality Index, the Self-Compassion Scale, the Epworth Sleepiness Scale, the Hospital Anxiety and Depression Scale, and the World Health Organization Subjective Well-Being Index. The final sample consisted of 615 students (82% female, mean age: 23.4 ± 6.5 years), of whom 108 (18%) had positive bimodality indexes. Bimodal subjects comprised 48 students, 8% of the total sample. Bimodal subjects had poorer subjective sleep quality, more daytime sleepiness, lower subjective well-being, greater anxiety and depression symptoms, and lower self-compassion than morning and/or intermediate types; they did not differ from evening types. The description of bimodal diurnal preference in this population may be of interest for the design of academic policies more in line with the circadian reality of students.