Sleep Initiation Research Articles

Factors Associated with Sleep Disorder among Korean Cancer Survivors: A Cross-Sectional Study.

The factors associated with sleep disorder are controversial. This study aimed to evaluate the prevalence of sleep disorder and the factors associated with sleep disorder among Korean adult cancer survivors. In this cross-sectional study, we collected data on sleep problems as outcome variables, and sociodemographic and clinical information as predictor variables from cancer survivors at two university-affiliated hospitals. Sleep disorder was defined as "a difficulty in sleep initiation or sleep maintenance at least 3 times a week that started after a cancer diagnosis." Multiple logistic regression analysis was performed with odds ratios (OR) and 95% confidence intervals (95% CI) to evaluate the factors associated with sleep disorder. The participants were 1,893 Korean cancer survivors (mean age, 58.1 years; females 68.0%). The prevalence of sleep disorder among male and female cancer survivors were 16.5% and 20.3%, respectively. An increase of age by 1-year was associated with a 1.04 (95% CI, 1.01-1.07; P=0.011) times higher risk of sleep disorder in males, while an inverse association was found in females. In female survivors, high fear of cancer recurrence (FCR), high anxiety, menopause, and high EuroQol Visual Analog Scale were associated with 1.45 (95% CI, 1.06-1.98; P=0.020), 1.78 (95% CI, 1.25-2.55; P=0.002), 1.70 (95% CI, 1.08-2.67; P=0.022), and 0.59 (95% CI, 0.43-0.82; P=0.002) times higher risk of sleep disorder, respectively. In male survivors, living with a spouse/or partner was associated with 57% (95% CI, 0.20-0.95; P=0.036) lower risk of sleep disorder. Analyses of cancer sites showed that the factors associated with sleep disorder varied across cancer sites. One-fifth of adult cancer survivors had sleep disorder. Age, menopausal status, FCR, anxiety, living with a spouse or partner, and quality of life were independently associated with sleep disorder in Korean cancer survivors.

Closed-Loop Auditory Stimulation to Guide Respiration: Preliminary Study to Evaluate the Effect on Time Spent in Sleep Initiation during a Nap.

Various stimulation systems to modulate sleep structure and function have been introduced. However, studies on the time spent in sleep initiation (TSSI) are limited. This study proposes a closed-loop auditory stimulation (CLAS) to gradually modulate respiratory rhythm linked to the autonomic nervous system (ANS) activity directly associated with sleep. CLAS is continuously updated to reflect the individual's current respiratory frequency and pattern. Six participants took naps on different days with and without CLAS. The average values of the TSSI are 14.00 ± 4.24 and 9.67 ± 5.31 min in the control and stimulation experiments (p < 0.03), respectively. Further, the values of respiratory instability and heart rate variability differ significantly between the control and stimulation experiments. Based on our findings, CLAS supports the individuals to gradually modulate their respiratory rhythms to have similar characteristics observed near sleep initiation, and the changed respiratory rhythms influence ANS activities, possibly influencing sleep initiation. Our approach aims to modulate the respiratory rhythm, which can be controlled intentionally. Therefore, this method can probably be used for sleep initiation and daytime applications.

A Cross-Sectional Study of Sleep Disturbances in Children and Adolescents With Abdominal Pain-Associated Disorders of Gut-Brain Interaction.

The aims of the current study were to determine the frequencies of specific sleep disturbances in youth with abdominal pain-associated disorders of gut-brain interaction (AP-DGBIs) and to assess relationships with psychological dysfunction. This was a retrospective evaluation of 226 consecutive patients diagnosed with an AP-DGBI. All had undergone a systematic evaluation of gastrointestinal symptoms, the Sleep Disturbance Scale for Children, and the Behavior Assessment System for Children. Disorders of initiation and maintenance of sleep (DIMS; 40%) and disorders of excessive daytime somnolence (DOES; 14%) were each present in more than 10% of the patients. Both DIMS and DOES scores were more likely to be elevated in patients with anxiety and/or depression scores in the at-risk or elevated-risk ranges. Sleep disorders are common in youth with AP-DGBIs and are associated with anxiety and depression, even in those patients with anxiety and depression in the at-risk range.

Prolonged Use of an Automated Insulin Delivery System Improves Sleep in Long-Standing Type 1 Diabetes Complicated by Impaired Awareness of Hypoglycemia.

This study assessed changes in actigraphy-estimated sleep and glycemic outcomes after initiating automated insulin delivery (AID). Ten adults with long-standing type 1 diabetes and impaired awareness of hypoglycemia (IAH) participated in an 18-month clinical trial assessing an AID intervention on hypoglycemia and counter-regulatory mechanisms. Data from eight participants (median age = 58 years) with concurrent wrist actigraph and continuous glucose monitoring (CGM) data were used in the present analyses. Actigraphs and CGM measured sleep and glycemic control at baseline (one week) and months 3, 6, 9, 12, 15, and 18 (three weeks) following AID initiation. HypoCount software integrated actigraphy with CGM data to separate wake and sleep-associated glycemic measures. Paired sample t-tests and Cohen's d effect sizes modeled changes and their magnitude in sleep, glycemic control, IAH (Clarke score), hypoglycemia severity (HYPO score), hypoglycemia exposure (CGM), and glycemic variability (lability index [LI]; CGM coefficient-of-variation [CV]) from baseline to 18 months. Sleep improved from baseline to 18 months (shorter sleep latency [P < .05, d = 1.74], later sleep offset [P < .05, d = 0.90], less wake after sleep onset [P < .01, d = 1.43]). Later sleep onset (d = 0.74) and sleep midpoint (d = 0.77) showed medium effect sizes. Sleep improvements were evident from 12 to 15 months after AID initiation and were preceded by improved hypoglycemia awareness (Clarke score [d = 1.18]), reduced hypoglycemia severity (HYPO score [d = 2.13]), reduced sleep-associated hypoglycemia (percent time glucose was < 54 mg/dL, < 60 mg/dL,< 70 mg/dL; d = 0.66-0.81), and reduced glucose variability (LI, d = 0.86; CV, d = 0.62). AID improved sleep initiation and maintenance. Improved awareness of hypoglycemia, reduced hypoglycemia severity, hypoglycemia exposure, and glucose variability preceded sleep improvements.This trial is registered with ClinicalTrials.gov NCT03215914 https://clinicaltrials.gov/ct2/show/NCT03215914.

Regional variability in intracerebral properties of NREM to REM sleep transitions in humans

Transitions between wake and sleep states show a progressive pattern underpinned by local sleep regulation. In contrast, little evidence is available on non-rapid eye movement (NREM) to rapid eye movement (REM) sleep boundaries, considered as mainly reflecting subcortical regulation. Using polysomnography (PSG) combined with stereoelectroencephalography (SEEG) in humans undergoing epilepsy presurgical evaluation, we explored the dynamics of NREM-to-REM transitions. PSG was used to visually score transitions and identify REM sleep features. SEEG-based local transitions were determined automatically with a machine learning algorithm using features validated for automatic intra-cranial sleep scoring (10.5281/zenodo.7410501). We analyzed 2988 channel-transitions from 29 patients. The average transition time from all intracerebral channels to the first visually marked REM sleep epoch was 8 s ± 1 min 58 s, with a great heterogeneity between brain areas. Transitions were observed first in the lateral occipital cortex, preceding scalp transition by 1 min 57 s ± 2 min 14 s (d = -0.83), and close to the first sawtooth wave marker. Regions with late transitions were the inferior frontal and orbital gyri (1 min 1 s ± 2 min 1 s, d = 0.43, and 1 min 1 s ± 2 min 5 s, d = 0.43, after scalp transition). Intracranial transitions were earlier than scalp transitions as the night advanced (last sleep cycle, d = -0.81). We show a reproducible gradual pattern of REM sleep initiation, suggesting the involvement of cortical mechanisms of regulation. This provides clues for understanding oneiric experiences occurring at the NREM/REM boundary.

High Prescribing and State-Level Variation in Z-Drug Use Among Medicare Patients.

Z-drugs are nonbenzodiazepine hypnotics used for sleep initiation and maintenance; these drugs increase the risk of fall-related injuries in older adults. The American Geriatrics Society's Beers criteria classifies Z-drugs as high-risk and strongly recommends avoiding prescribing Z-drugs to older adults due to adverse effects. The study objectives were to determine the prevalence of Z-drug prescribing among Medicare Part D patients and identify state or specialty-dependent prescribing differences. This study also aimed to determine prescribing patterns of Z-drugs to Medicare patients. Z-drug prescription data was extracted from the Centers for Medicare and Medicaid Services State Drug Utilization Data for 2018. For all 50 states, the number of prescriptions per 100 Medicare enrollees and days-supply per prescription was determined. The percentage of total prescriptions prescribed by each specialty and the average number of prescriptions per provider within each specialty was also determined. Zolpidem was the most prescribed Z-drug (95.0%). Prescriptions per 100 enrollees were significantly high in Utah (28.2) and Arkansas (26.7) and significantly low in Hawaii (9.3) relative to the national average (17.5). Family medicine (32.1%), internal medicine (31.4%), and psychiatry (11.7%) made up the largest percentages of total prescriptions. The number of prescriptions per provider was significantly high among psychiatrists. Contrary to the Beers criteria, Z-drugs are prescribed to older adults at high rates.

Does EGFR Signaling Mediate Orexin System Activity in Sleep Initiation?

Sleep-wake cycle disorders are an important symptom of many neurological diseases, including Parkinson's disease, Alzheimer's disease, and multiple sclerosis. Circadian rhythms and sleep-wake cycles play a key role in maintaining the health of organisms. To date, these processes are still poorly understood and, therefore, need more detailed elucidation. The sleep process has been extensively studied in vertebrates, such as mammals and, to a lesser extent, in invertebrates. A complex, multi-step interaction of homeostatic processes and neurotransmitters provides the sleep-wake cycle. Many other regulatory molecules are also involved in the cycle regulation, but their functions remain largely unclear. One of these signaling systems is epidermal growth factor receptor (EGFR), which regulates the activity of neurons in the modulation of the sleep-wake cycle in vertebrates. We have evaluated the possible role of the EGFR signaling pathway in the molecular regulation of sleep. Understanding the molecular mechanisms that underlie sleep-wake regulation will provide critical insight into the fundamental regulatory functions of the brain. New findings of sleep-regulatory pathways may provide new drug targets and approaches for the treatment of sleep-related diseases.

0419 Sensitivity of ORP to classify individuals with insomnia based on subjective complaints

Abstract Introduction The diagnosis of insomnia is currently based on subjective complaints. Previous research has demonstrated limited benefits of polysomnography in improving diagnostic accuracy with no evident differences in sleep macro-architecture and traditional indices of sleep quality. In this study, we aimed to assess the ability of a novel index of sleep quality, the Odds Ratio Product (ORP), to correctly identify individuals with insomnia, based on subjective complaints. Methods We analyzed responses to a custom sleep survey from 510 participants (age 46.2±12.4; 229 females). We entered 13 outcomes to a principal component analysis (PCA). These included age, body mass index (BMI), Epworth Sleepiness Scale (ESS) scores, sex, questions about snoring, subjective hours of sleep, satisfaction with own sleep, movement symptoms, problems falling asleep, staying asleep and waking up early. Based on the correlations between the original outcomes, the PCA extracted 3 factors that were interpreted as 3 different phenotypes: 1) insomnia (e.g., sleep initiation and maintenance complaints, satisfaction with sleep, lower subjective sleep duration); 2) OSA (e.g., bed partner snoring complaints, snoring self-awareness, sleepiness, respiratory complaints); 3) movement disorder (e.g., movements, female, lower age, higher BMI). We then computed the pre-test probability of insomnia (factor 1 scores &amp;gt;80%) and conducted a series of ROC analyses to assess specificity of PSG indices traditionally used to evaluate the presence of insomnia, and of ORP metrics. Results The AUC values assessing the ability of ORP metrics to predict 80% pre-test probability of insomnia were: ORPwake (0.592, 95% CI 0.499-0.685), ORPNREM (0.465, 95% CI 0.362-0.558), ORPREM (0.542, 95% CI 0.447-0.636), and ORPTRT (0.567, 95% CI 0.475-0.659). When looking at traditional indices like total sleep time (TST), wake after sleep onset (WASO), and number of awakenings, the AUC values were 0.471 (95% CI 0.385-0.556), 0.612 (95% CI 0.528-0.697) and 0.509 (95% CI 0.421-0.597), respectively. Conclusion WASO, ORPwake and ORPTRT have the highest sensitivity to detect insomnia in participants with &amp;gt;80% pretest probability measured by subjective complaints. These analyses indicate the value of EEG metrics of sleep quality to correctly identify individuals with insomnia and the need to investigate both sleep and wake states. Support (if any)

0150 Increased Prevalence of Clinical Depression in Late Teens with Sleep Complaints

Abstract Introduction Adolescent mental health is becoming clinical attention since suicide is one of the leading causes of death in late teens. Depression and sleep are interconnected, since depression affects sleep, vice versa. Clinical depression with symptoms of sleep disturbance were interviewed by a board certified psychiatrist following depression inventory. Age, sex matched adolescents were also accessed by depression inventory scales. Methods 71 adolescence aged from 16-18 ( M:F=1:1) who visited sleep disorders clinic for their complaints of daytime sleepiness, sleep initiation problems, snoring, frequent midnight awakenings. 29% of them diagnosed with narcolepsy, 21% delayed sleep phase syndrome, 19% obstructive sleep apnea syndrome, 15% of them had chronic insomnia. Some of them have multiple sleep disorders associated diagnosis like OSA + narcolepsy, OSA + insomnia, or DSPS + OSA. 21 aged, sex matched high school students were evaluated for their anxiety and depression symptoms. Results Patients with sleep complaints had higher level of emotional distress compared with healthy adolescents without sleep complaints. Among sleep disorders, patients with narcolepsy had higher level of depression. These explains why children or adolescents with narcolepsy are initially misdiagnosed with depression in clinical setting. Comorbid depression and narcolepsy should be differentiated in clinical field. Conclusion In adolescents, patients with sleep disorders especially with narcolepsy have higher level of depression. Misdiagnosis of narcolepsy as depression may delay narcolepsy diagnosis. Support (if any)

Treatment strategy for insomnia disorder: Japanese expert consensus.

There is a lack of evidence regarding answers for clinical questions about treating insomnia disorder. This study aimed to answer the following clinical questions: (1) how to use each hypnotic and non-pharmacological treatment differently depending on clinical situations and (2) how to reduce or stop benzodiazepine hypnotics using alternative pharmacological and non-pharmacological treatments. Experts were asked to evaluate treatment choices based on 10 clinical questions about insomnia disorder using a nine-point Likert scale (1 = "disagree" to 9 = "agree"). The responses of 196 experts were collected, and the answers were categorized into first-, second-, and third-line recommendations. The primary pharmacological treatment, lemborexant (7.3 ± 2.0), was categorized as a first-line recommendation for sleep initiation insomnia, and lemborexant (7.3 ± 1.8) and suvorexant (6.8 ± 1.8) were categorized as the first-line recommendations for sleep maintenance insomnia. Regarding non-pharmacological treatments for primary treatment, sleep hygiene education was categorized as the first-line recommendation for both sleep initiation (8.4 ± 1.1) and maintenance insomnia (8.1 ± 1.5), while multicomponent cognitive behavioral therapy for insomnia was categorized as the second-line treatment for both sleep initiation (5.6 ± 2.3) and maintenance insomnia (5.7 ± 2.4). When reducing or discontinuing benzodiazepine hypnotics by switching to other medications, lemborexant (7.5 ± 1.8) and suvorexant (6.9 ± 1.9) were categorized as first-line recommendations. Expert consensus indicates that orexin receptor antagonists and sleep hygiene education are recommended as first-line treatments in most clinical situations to treat insomnia disorder.

0679 Do Individuals with ADHD and Sleep Disorders Symptoms Exhibit Worse Executive Function?

Abstract Introduction Sleep disorders in individuals with Attention Deficit Hyperactivity Disorder (ADHD) are more prevalent than in people without ADHD. Given that sleep disorders (e.g., insomnia and OSA) impact daytime function (e.g., mood, memory, motivation, attention, executive function [EF], etc.), it is reasonable to wonder if these domains interact. Thus, the aim of the present analysis was to evaluate subjects diagnosed with ADHD who were also symptomatic for insomnia or OSA on a self-report measure of executive function. The hypothesis for the analysis being: subjects with insomnia would show more severe executive function deficits as compared to subjects without symptoms of insomnia and/or subjects with OSA. Methods This analysis includes data from 149 subjects diagnosed with ADHD (38% female, Mage 32.8±13.2yrs). Sleep disorder and EF data was provided by the Penn ADHD Treatment and Research Program. Database assessments were gathered from intakes, which included the SDS-CL-25 (a comprehensive screener for sleep disorders) and the BDEFS-LF (a self-report measure of EF deficit). In order to type individuals as “symptom positive” for insomnia or OSA, subjects were required to score &amp;gt;3 for any item within each category. These groups were then compared for their scores on the BDEFS-LF (total score and for three factor scores: self-restraint score [BDEFS-SR], self-regulation of emotions score [BDEFS-SRM], and self-motivation score [BDEFS-SM]). Results Subjects with-and-without insomnia symptoms were not found to significantly differ on the BDEFS-T, or any of the three sub-scales. In contrast, subjects with-and-without OSA symptoms significantly differed on the BDEFS-T (p=0.0328), and on two of the three sub-scales (BDEFS-SR [p=0.0183] &amp; BDEFS-SRM [p=0.0032]). Conclusion Contrary to our hypothesis, it was the symptom positive OSA group that showed the most deficits on executive function (as measured by the BDEFS-T). This suggests that, in people with ADHD, sleep fragmentation and/or hypoxia may be more associated with EF deficits than problems with sleep initiation or maintenance. This said, it is also possible that other measures of insomnia that better represent sleep insufficiency and/or total nocturnal wakefulness may be more associated with executive functioning deficits, alone or in combination with the sleep sequela of OSA. Support (if any)

Encouraging Continuous Positive Airway Pressure Adherence With Personalized Strategies

Objectives: This study aimed to elucidate whether a comprehensive intervention focusing on individual characteristics could enhance adherence to Continuous Positive Airway Pressure (CPAP) in patients with Obstructive Sleep Apnea (OSA).Methods: We conducted a single-arm, pilot intervention study, recruiting participants aged ≥20 years with suspected OSA. All participants underwent split-night polysomnography and received standardized CPAP treatment. We identified five categories of factors contributing to poor CPAP adherence: mouth breathing, high CPAP pressure causing sleep initiation difficulties, bradypnea or hyperpnea before sleep onset, postarousal central apnea, and nasal dryness and obstruction. We objectively measured CPAP adherence data at 1, 3, 6 and 12 months after a comprehensive intervention targeting individual characteristics. We analyzed the trends in CPAP adherence rates over 1 year.Results: A total of 48 participants (74.0% males; 56.9±13.9 years old) were followed up for 12 months. CPAP adherence rate was 77.1% at 1 month; declined to 60.4%, 39.6%, and 31.3% at 3, 6, and 12 months, respectively. There was no significant difference in demographic and psychological factors, sleep-related symptoms, and sleep characteristics between the adherence and the non-adherence groups. Low body mass index was an independent risk factor affecting CPAP adherence (odds ratios 0.78, &lt;i&gt;p&lt;/i&gt;=0.04).Conclusions: Although our study did not yield significant improvements in CPAP adherence through the comprehensive intervention that targeted individual characteristics, it is significant because it attempted to provide a multidimensional approach to intervention, rather than targeting a single aspect, in promoting CPAP adherence.

就寝前の洗口液使用が睡眠に及ぼす影響：腕時計型心拍数計を用いたフィールド睡眠研究

This study aimed to test the efficacy of a mint-flavored mouthwash when it is used at bedtime for subsequent sleep in a field study setting, using a wristwatch-type heart rate (HR) monitoring devise. Using a within-subject experimental design, twenty healthy adults used three types of mouthwash having a different intensity of mint sensation (or water as a control) per one experiment night just before going to bed at their home environment, in a counterbalanced order. As for results, irrespective of the intensity of mint-flavored mouthwashes, the subjective score for “fatigue” and “refreshing” before sleep was decreased and increased, respectively. In addition, although a significant inhibition of HR decline in the sleep initiation period (0-30 minutes after bedtime) was observed with the use of mint-flavored mouthwashes compared with the control, the trend reversed subsequently as HR trended lower than for the control during 2-6 hour after the bedtime. These findings suggest that the using mint-flavored mouthwashes at bedtime induces a positive mood before sleep and may improve physiological sleep. Moreover, this study illustrated the possible application and significant advantage of the use of wristwatch-type heart rate monitoring devise in a context of field study.

The Assessment and Management of Insomnia Among Older Adults

As many as 50% of older adults have concerns regarding the initiation or maintenance of sleep. The underdiagnosis or misdiagnosis of sleep disorders can cause significant complications in the elderly, and this symposium aims to provide the geriatric specialist with the knowledge and tools to evaluate and treat common sleep concerns. The session will open with a brief introduction overviewing the epidemiology and significance of insomnia. Dr. Srinivasan will open with a review of the physiologic stages of the sleep cycle. She will also discuss age-related changes in sleep architecture that clinicians should be aware of when conceptualizing sleep in elderly patients.In section 2, Dr. Johnson will review the evaluation of insomnia in older adults, with a focus on differential diagnosis of sleep disorders. Insomnia will be sub-divided into initial, middle, and terminal insomnia and include brief overviews of obstructive sleep apnea, parasomnias including REM sleep behavior disorder, restless legs syndrome, and factors impacting the circadian cycle. Screening tools and scales to assist in the evaluation of sleep disorders will also be discussed.Section 3 will be an overview of non-pharmacological interventions from Dr. Srinivasan. She will review the evidence for Cognitive Behavioral Therapy for Insomnia (CBT-I) and also discuss the core components of CBT-I. While sleep hygiene and behavioral therapies are usually considered first line treatment, pharmacotherapy may be beneficial as adjunctive treatment in patients with persistent insomnia who are unable to pursue cognitive behavioral therapies. According to the medical literature, both treatment modalities have been found to yield similar short-term outcomes, while CBT-I has been shown to yield better long-term outcomes. In the 4th section of the session, Dr. Dix will provide an overview of different classes of pharmacological interventions for insomnia, discussing a variety of treatments and their mechanism of action, dosing, efficacy, risks, and benefits. Prior to allowing time for questions from the audience, Dr. Tampi will briefly discuss the practical application of available evidence in managing insomnia among older adults.

Effects of curcumin supplementation on insomnia and daytime sleepiness in young women with premenstrual syndrome and dysmenorrhea: Arandomized clinical trial.

Premenstrual syndrome and primary dysmenorrhea are common gynecological complaints that are associated with psychological disorders. There is increasing evidence for the neuroprotective properties of curcumin, a polyphenolic natural product. This study aimed to assess the effects of curcumin on sleep complications in women with premenstrual syndrome and dysmenorrhea. This triple-masked, placebo-controlled clinical trial comprised 124 patients with both premenstrual syndrome and dysmenorrhea. Participants were randomly assigned to curcumin (n=57) or control (n=60) groups. Each participant received one capsule containing either 500 mg of curcumin plus piperine or placebo, daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles. Insomnia and sleepiness were assessed using standard questionnaires. Scores for insomnia and daytime sleepiness were directly correlated with the Premenstrual Syndrome Screening Tool (PSST) score (p<0.05), but not with the visual analogue scale (VAS) score at baseline (p>0.05). There was a non-significant reduction in insomnia and sleepiness scores in both curcumin and placebo groups after the study intervention. Whilst, improvement rate of insomnia status, daytime sleepiness severity, short sleep duration and difficult sleep initiation was not statistically significant between the curcumin and placebo groups. Curcumin does not significantly affect sleep disorders in young women with premenstrual syndrome and dysmenorrhea.

Frustration Intolerance, Self-Efficacy and Sleep Quality in Medical Students During Pandemic of Covid-19

Introduction: A novel coronavirus disease (COVID-19) was initially reported in China in December 2019. In a few months, the virus spread rapidly across the globe, and on 30 January 2020 the World Health Organization (WHO) declared the outbreak to be a Public Health Emergency of International Concern. Objectives: The main objective of the study is to find the frustration intolerance, self-efficacy and sleep quality in medical students during pandemic of COVID-19. Material and methods: This cross sectional study was conducted in University of Lahore during 2021-2022. The data was collected through questionnaire. The questionnaire covered sleep conditions, stores of infection control supplies, mood and stress, usage of social media and sources of acquiring COVID-19 information, risk perception, and sociodemographic data. Results: The data was collected from 200 patients. About half of them were young-aged (55.0%) and married (49.1%). In terms of social media use, 57.8% spent more than 2 h per day. With regard to sleep deterioration after the COVID-19 outbreak, the weighted proportions of those who reported worsening sleep quality, worsening sleep initiation, and shortened sleep duration were 38.3%, 29.8%, and 29.1%, respectively. The weighted prevalence of current clinical insomnia was estimated at 29.9%. Practical implication: This study will help to find out the effect of COVID-19 on sleep quality, sleep initiation and duration among Pakistani population. Conclusion: It is concluded that COVID-19 is widely spreading in Pakistan and it effects on their sleep quality, sleep initiation, and sleep duration had worsened since the outbreak of COVID-19. This study identified high prevalence of frustration intolerance and poor sleep quality in medical students during pandemic of Covid-19. Keywords: COVID-19, Prevalence, Frustration, Pakistan, Sleep, Identify

Tripping on the edge of consciousness.

Herein the major accomplishments, trials and tribulations, and epiphanies experienced by James M. Krueger over the course of his career in sleep research are presented. They include the characterization of a) the supranormal EEG delta waves occurring during NREMS post sleep loss, b) Factor S as a muramyl peptide, c) the physiological roles of cytokines in sleep regulation, d) multiple other sleep regulatory substances, e) the dramatic changes in sleep over the course of infectious diseases, and f) sleep initiation within small neuronal/glial networks. The theory that the preservation of brain plasticity is the primordial sleep function is briefly discussed. These accomplishments resulted from collaborations with many outstanding scientists including James M. Krueger's mentors (John Pappenheimer and Manfred Karnovsky) and collaborators later in life, including Charles Dinarello, Louis Chedid, Mark Opp, Ferenc Obal jr., Dave Rector, Ping Taishi, Linda Toth, Jeannine Majde, Levente Kapas, Eva Szentirmai, Jidong Fang, Chris Davis, Sandip Roy, Tetsuya Kushikata, Fabio Garcia-Garcia, Ilia Karatsoreos, Mark Zielinski, and Alok De, plus many students, e.g. Jeremy Alt, Kathryn Jewett, Erika English, and Victor Leyva-Grado.

Neuro-orchestration of sleep and wakefulness.

Although considered an inactive state for centuries, sleep entails many active processes occurring at the cellular, circuit and organismal levels. Over the last decade, several key technological advances, including calcium imaging and optogenetic and chemogenetic manipulations, have facilitated a detailed understanding of the functions of different neuronal populations and circuits in sleep-wake regulation. Here, we present recent progress and summarize our current understanding of the circuitry underlying the initiation, maintenance and coordination of wakefulness, rapid eye movement sleep (REMS) and non-REMS (NREMS). We propose a de-arousal model for sleep initiation, in which the neuromodulatory milieu necessary for sleep initiation is achieved by engaging in repetitive pre-sleep behaviors that gradually reduce vigilance to the external environment and wake-promoting neuromodulatory tone. We also discuss how brain processes related to thermoregulation, hunger and fear intersect with sleep-wake circuits to control arousal. Lastly, we discuss controversies and lingering questions in the sleep field.

SLEEP DURATION MEDIATES THE RELATIONSHIP BETWEEN LETTER FLUENCY AND COGNITION

Abstract Changes in cognition are a normative part of aging. Verbal fluency is widely used for assessing cognitive function, including predicting mild cognitive impairment. As people age, sleep duration and quality decrease. This has been associated with cognitive decline; individuals with low-quality sleep (fewer hours and difficulties with initiation or maintenance of sleep) are more likely to complain of poorer cognition. Lack of sleep is detrimental to verbal fluency (word production). Longer sleep has been linked to memory deficits and is a potential indicator of mild cognitive impairment. This study aimed to address the relationship between verbal fluency and cognitive function as mediated by sleep duration. Participants included 31 middle-aged adults (female, n=19;age=53.55±7.18yrs) and 24 older adults (female=14; age=70.33±3.69yrs). The MoCA assessed cognitive functioning. Verbal fluency (90 seconds each) was measured via category word (animals; semantic verbal fluency) and letter word (phonemic verbal fluency; F,A,S). Mediation models used Baron and Kenny’s (1986) approach for estimating mediation effects, controlling for age and education. Category results were non-significant. However, sleep duration partially mediated the relationship between letter fluency for each letter and cognitive function, respectively (F:F(2,52)=7.31, p=.002, R2=.22; A: F(2,52)=3.80, p=.029, R2=.18; S: F(2,52)=5.47, p=.007, R2=.17). Sleep hours were negatively associated with letter fluency, meaning fewer hours of sleep improved fluency performance, which in turn was positively associated with MOCA scores (F: b=-.378, 95%CI [-0.64, 0.02]; A: b=-.172, 95%CI [-0.42, 0.01]; S: b=-.24, 95%CI [-0.64, 0.02]. This coincides with the abovementioned literature and helps further understand how sleep and cognitive performance are related.

Associations between demographic and parental factors and infant sleep characteristics.

Although sleep problems are highly prevalent in infants, the intrinsic and extrinsic factors that influence sleep consolidation and regulation in this age group are not well understood. This study aimed to examine the cross-sectional associations of demographic and parental factors with infant sleep characteristics. Participants were 97 Canadian mother-infant dyads primarily from Edmonton, Alberta. Demographic factors (e.g., infant age), parenting practices (e.g., sleep position, sleep initiation methods), and infants sleep characteristics (e.g., the frequency of nighttime awakenings) were assessed using the Brief Infant Sleep Questionnaire. Maternal sleep characteristics (e.g., nighttime sleep duration) were assessed using Actigraph accelerometers. Infant age (mean = 4.24 ± 2.90) was associated with most infant sleep characteristics. In multiple regression models for infant nighttime sleep duration, after removing influential observations, a negative association for side (vs. prone) sleep position was, respectively, observed. In multiple regression models for the frequency of nighttime awakenings in infants, positive associations for infants falling asleep while feeding (vs. in bed alone) and side (vs. prone) sleep position were consistently observed after removing influential observations. Lower nighttime sleep efficiency (B = - 0.08, 95%CI: -0.13, -0.02) and longer nighttime wake after sleep onset (B = 1.03, 95%CI: 0.41, 1.65) in mothers were associated with more frequent nighttime awakenings in infants. After removing influential observations, more frequent nighttime awakenings (B = 0.35; 95%CI: 0.09, 0.61) and longer total sleep duration (B = 0.33, 95%CI: 0.11, 0.55) in mothers were also associated with more frequent nighttime awakenings in infants. Sleep initiation methods with less parental involvement, and more continuous and efficient maternal nighttime sleep, tended to be associated with less interrupted infant sleep.