Orexin 2 receptor-selective agonist danavorexton (TAK-925) promotes wakefulness in non-human primates and healthy individuals.

The orexin 2 receptor-selective agonist danavorexton (TAK-925) has been shown to produce wake-promoting effects in wild-type mice, narcolepsy-model mice, and individuals with narcolepsy type 1 and type 2. Here, we report wake-promoting effects of danavorexton in non-human primates and healthy men during their sleep phase. Electroencephalogram analyses revealed that subcutaneous administration of danavorexton significantly increased wakefulness in common marmosets (p < 0.05 at 0.1 mg kg-1 , and p < 0.001 at 1 mg kg-1 and 10 mg kg-1 ) and cynomolgus monkeys (p ≤ 0.05 at 1 mg kg-1 and 3 mg kg-1 ). In a phase 1b crossover, randomized, double-blind, placebo-controlled and active-controlled study in sleep-deprived healthy participants (ClinicalTrials.gov identifier: NCT03522506), modafinil 300 mg (used to demonstrate assay sensitivity) and continuous infusion of danavorexton 44 mg and danavorexton 112 mg showed statistically superior wake-promoting effects to placebo (n = 18). Measured using the Maintenance of Wakefulness Test, mean (standard deviation) sleep latencies during infusion of danavorexton 44 mg, danavorexton 112 mg and placebo were 21.4 (8.9), 31.8 (3.2) and 9.2 (6.4) min, respectively. Least-squares mean difference from placebo in average sleep latency was 16.8 min with danavorexton 44 mg and 30.2 min with danavorexton 112 mg (both p < 0.001). Karolinska Sleepiness Scale scores were statistically significantly lower (indicating decreased sleepiness) for participants receiving danavorexton than for those receiving placebo during infusion (danavorexton 44 mg, p = 0.010; danavorexton 112 mg, p < 0.001). Together, these results indicate that an orexin 2 receptor agonist increases wakefulness in non-human primates and healthy individuals during their sleep phase.

Co-activation of rhythms during alpha band oscillations as an interictal biomarker of exploding head syndrome.

BACKGROUND: Exploding head syndrome is a rarely reported benign sensory parasomnia that may nonetheless have significant impact on patients' quality of life and their perceived well-being. To date, the mechanisms underlying attacks, characterised by a painless perception of abrupt, loud noises at transitional sleep-wake or wake-sleep states, are by and large unclear. METHODS AND RESULTS: In order to address the current gap in the knowledge of potential underlying pathophysiology, a retrospective case-control study of polysomnographic recordings of patients presenting to a tertiary sleep disorders clinic with exploding head syndrome was conducted. Interictal (non-attack associated) electroencephalographic biomarkers were investigated by performing macrostructural and event-related dynamic spectral analyses of the whole-night EEG. In patients with exploding head syndrome, additional oscillatory activity was recorded during wakefulness and at sleep/wake periods. This activity differed in its frequency, topography and source from the alpha rhythm that it accompanied. CONCLUSION: Based on these preliminary findings, we hypothesise that at times of sleep-wake transition in patients with exploding head syndrome, aberrant attentional processing may lead to amplification and modulation of external sensory stimuli.

Criteria in diagnosing nocturnal leg cramps: a systematic review.

BACKGROUND: Up to 33% of the general population over 50 years of age are affected by nocturnal leg cramps. Currently there are no generally accepted clinical characteristics, which identify nocturnal leg cramps. This study aims to identify these clinical characteristics and to differentiate between them and the characteristics of restless leg syndrome and periodic limb disorder. METHOD: A systematic literature study was executed from December 2015 to May 2016. This study comprised of a systematic literature review of randomized clinical trials, observational studies on nocturnal and rest cramps of legs and other muscles, and other systematic and narrative reviews. Two researchers independently extracted literature data and analyzed this using a standardized reviewing protocol. Modified versions of the Cochrane Collaboration tools assessed the risk of bias. A Delphi study was conducted to assess agreement on the characteristics of nocturnal leg cramps. RESULTS: After systematic and manual searches, eight randomized trials and ten observational studies were included. On the basis of these we identified seven diagnostic characteristics of nocturnal leg cramps: intense pain, period of duration from seconds to maximum 10 minutes, location in calf or foot, location seldom in thigh or hamstrings, persistent subsequent pain, sleep disruption and distress. CONCLUSION: The seven above characteristics will enhance recognition of the condition, and help clinicians make a clear distinction between NLC and other sleep-related musculoskeletal disorder among older adults.

An at-home evaluation of a light intervention to mitigate sleep inertia symptoms.

OBJECTIVES: Under laboratory settings, light exposure upon waking at night improves sleep inertia symptoms. We investigated whether a field-deployable light source would mitigate sleep inertia in a real-world setting. METHODS: Thirty-six participants (18 female; 26.6 years ± 6.1) completed an at-home, within-subject, randomized crossover study. Participants were awoken 45 minutes after bedtime and wore light-emitting glasses with the light either on (light condition) or off (control). A visual 5-minute psychomotor vigilance task, Karolinska sleepiness scale, alertness and mood scales, and a 3-minute auditory/verbal descending subtraction task were performed at 2, 12, 22, and 32 minutes after awakening. Participants then went back to sleep and were awoken after 45 minutes for the opposite condition. A series of mixed-effect models were performed with fixed effects of test bout, condition, test bout × condition, a random effect of the participant, and relevant covariates. RESULTS: Participants rated themselves as more alert (p = .01) and energetic (p = .001) in the light condition compared to the control condition. There was no effect of condition for descending subtraction task outcomes when including all participants, but there was a significant improvement in descending subtraction task total responses in the light condition in the subset of participants waking from N3 (p = .03). There was a significant effect of condition for psychomotor vigilance task outcomes, with faster responses (p < .001) and fewer lapses (p < .001) in the control condition. CONCLUSIONS: Our findings suggest that light modestly improves self-rated alertness and energy after waking at home regardless of sleep stage, with lower aggression and improvements to working memory only after waking from N3. Contrary to laboratory studies, we did not observe improved performance on the psychomotor vigilance task. Future studies should include measures of visual acuity and comfort to assess the feasibility of interventions in real-world settings.

Emotional and behavioral features associated with subclinical hypothyroidism in children and adolescents with Down syndrome.

Background: Subclinical hypothyroidism (SH) is particularly frequent in individuals with Down syndrome (DS). Despite the amount of evidence suggesting SH is associated with psychopathological symptoms and sleep problems in general population, poor is known about the emotional and behavioral features associated with SH in children with DS. Objective: The first aim of the current study was to investigate differences in emotional and behavioral profiles between a group of children with DS exhibiting co-occurring SH and a group of age and BMI-matched children with DS without co-occurring SH. The second aim of the present study was to investigate differences in sleep disturbances between these groups. Methods: We included in this retrospective study 98 participants with DS aged 3-18 years with the aim to explore differences in emotional/behavioral problems as well as in sleep difficulties between children with DS with or without co-occurring SH. Results: Participants with co-occurring SH exhibited significantly higher scores at several scales of the Conners' Parent Rating Scales Long Version - Revised. However, they did not exhibit more sleep problems than control group. Conclusion: These results provide specific indications for psychological and neuropsychiatric evaluation of children with DS with suspected or diagnosed SH, highlighting the importance of a multidisciplinary approach in clinical care for children and adolescents with DS.

Impact of COVID-19 online classes on morningness-eveningness personality among adult college students: A survey study.

BACKGROUND: COVID-19 emerged as a serious pandemic in 2019 and billions of people were infected. Various precautionary methods were taken to contain the spread of virus such as social distancing, public lockdown, sanitation, and closure of schools and colleges. Many colleges started online classes to resume their syllabus and to complete the course curriculum. These evening online sessions resulted in late night sleep, long term mobile/computer exposure, and disturbed sleep pattern. OBJECTIVE: The present study aimed to determine the impact of COVID-19 online classes on morningness- eveningness personality and to compare it with different age groups, gender, and body mass index. METHODS: The cluster sampling method was used to collect the subjects from the total of 1153 adult college students, 897 subjects were selected based on the selection criteria and instructed to submit an online survey consists of the Morningness-eveningness Questionnaire and demographic and anthropometric data through mail, social media, or through a researcher by direct interview. RESULTS: The mean score for the 897 participants is 56.7, indicating intermediate morningness-eveningness personality type. On comparing the different groups, the youngest group (18-20 years) scored 4.23%(mean = 46.7), female subjects scored 6.13%(mean = 58.1), the underweight 2.67%(mean = 59.2) and overweight groups scored 2.89%(mean = 59.7) indicating definite eveningness. Among the 897 collected samples of the population 8.13%of the subjects experienced definite eveningness, 14.93%has moderate eveningness, 17.38%are under intermediate category, 22.4%have moderate morningness, and 37.11%have definite morningness. CONCLUSIONS: Subjects with eveningness personality have high risk of developing mental illness, thus it's important to determine the eveningness personality among student population to avoid serious complications in later age.

Attractor competition enriches cortical dynamics during awakening from anesthesia.

Slow oscillations (≲ 1 Hz), a hallmark of slow-wave sleep and deep anesthesia across species, arise from spatiotemporal patterns of activity whose complexity increases as wakefulness is approached and cognitive functions emerge. The arousal process constitutes an open window to the unknown mechanisms underlying the emergence of such dynamical richness in awake cortical networks. Here, we investigate the changes in network dynamics as anesthesia fades out in the rat visual cortex. Starting from deep anesthesia, slow oscillations gradually increase their frequency, eventually expressing maximum regularity. This stage is followed by the abrupt onset of an infra-slow (~0.2 Hz) alternation between sleep-like oscillations and activated states. A population rate model reproduces this transition driven by an increased excitability that brings it to periodically cross a critical point. Based on our model, dynamical richness emerges as a competition between two metastable attractor states, a conclusion strongly supported by the data.

Cotard parasomnia: le délire de negation that occur during the sleep-wake dissociation?

None: Unpleasant dreamlike mentation can occur during non-rapid eye movement parasomnias, leading to associated panic attacks. The mentations are rarely remembered and are likely underreported. However, they may lead to significant personal distress and, if not addressed, may contribute to poorer clinical outcomes. Cotard le délire de negation are very rare nihilistic delusions, historically described with psychotic disorders. Their association with a variety of neurologic disorders, including migraine and cluster-headache, has also been reported. Here we present three cases of Cotard parasomnia during which distinct states of consciousness defined by nihilistic ideation occurred. Patients described believing they are dead or dying, while unable to perceive or experience their bodies in whole, or in part, as their own. A source analysis of the electroencephalographic fingerprint of these mentations suggests right-hemispheric hypoactivity subsequent to confusional arousals. Mechanistically, an aberrant activation of two major intrinsic brain networks of wakefulness, the salience network and the default mode network, is argued.

Cotard's Parasomnia: Le Délire de Negation that occur during the Sleep-Wake Dissociation?

NONE: Unpleasant dreamlike mentation can occur during NREM parasomnias, leading to associated panic attacks. The mentations are rarely remembered, and are likely underreported. However, they may lead to significant personal distress, and if not addressed, may contribute to poorer clinical outcomes. Cotard's 'Le Délire de Negation', are very rare nihilistic delusions, historically described with psychotic disorders. Their association with variety of neurologic disorders, including migraine and cluster-headache, has also been reported. Here we present three cases of Cotard's parasomnia during which distinct states of consciousness defined by nihilistic ideation are reported. Patients described believing to be dead or dying, whilst unable to perceive or experience their bodies in whole, or in part, as their own. The source analysis of electroencephalographic fingerprint of these mentations suggests right hemispheric hypoactivity subsequent to confusional arousals. Mechanistically, an aberrant activation of two major intrinsic brain networks of wakefulness, the salience and the default-mode-network is argued.

Can we feel like being neither alert nor sleepy? The electroencephalographic signature of this subjective sub-state of wake state yields an accurate measure of objective sleepiness level.

Accurate measurement of objective level of sleepiness can have important implications for experimental and field studies of sleep deprived individuals. We proposed to accurately quantify changes in sleepiness level with single electroencephalographic (EEG) measures obtained from EEG spectra consisting of 16 spectral powers within the frequency interval from 1 to 16 Hz. The EEG signal was recorded every other hour from 19:00 of Friday to 19:00 of Sunday in 48 study participants. The differential spectra were calculated for the 1st minute with eyes closed as the differences between EEG spectra for pairs of distinct subjective sub-states (alert, neither alert nor sleepy, sleepy, and very sleepy sub-states scored on the Karolinska Sleepiness Scale as 3, 5, 7, and 9, respectively).The differential spectra were calculated for the sub-samples of those participants who succeeded and failed to succeed in completing all 25 EEG recording sessions (n = 25 and 23, respectively) and for the addition sample of 130 participants deprived from sleep for only one night. Single spectral EEG measures were then calculated by summation of 16 spectral powers weighted by a differential spectrum. The strongest correlation coefficients (0.981, 0.987, and 0.985) were attained between the time courses of subjective and objective measures when data on 130, 23 and 25 participants, respectively, were used for calculation of frequency waiting curve differentiating alert sub-sate either from sleepy sub-state or from neither alert nor sleepy sub-state. We recommended implementation of the proposed objective measure into experimental procedures requiring accurate estimation of objective sleepiness level.

Avaliação da qualidade do sono e sonolência diurna de um grupo de idosos / Assessment of sleep quality and daytime sleepiness in a group of elderly people

O objetivo do estudo foi avaliar a qualidade do sono e sonolência diurna de um grupo de idosos, verificar se há associação com prática de atividade física, presença de doença crônica, e Índice de Massa Corporal (IMC) e se há correlação com IMC, idade e qualidade de vida. Trata-se de um estudo transversal e descritivo. Para avaliação da qualidade do sono utilizou-se o Pittsburgh Sleep Quality Index (PSQI), para avaliação da sonolência diurna a Escala de Sonolência de Epworth (ESE) e para avaliação da qualidade de vida o WHOQOL-BREF. Foram avaliados 47 idosos com mediana (intervalo interquartil 25-75%) de 66 (62-70) anos de idade e IMC de 28,58 (26,21-30,44). 74,5% apresentaram sono ruim, 61,7% apresentaram Sonolência Diurna Normal e 97,8% classificados com boa qualidade de vida, com destaque para os domínios relações sociais (80%) e autoavaliação da qualidade de vida (80%). Apenas apresentou associação estatisticamente significativa a presença de qualidade de sono ruim com a prática de atividade física. Não houve associação entre presença de qualidade de sono ruim ou sonolência com IMC e presença de doença crônica. Houve uma correlação fraca, negativa e estatisticamente significativa apenas entre qualidade do sono com qualidade de vida (ρ=-0,466) e idade (ρ=-0,297). Conclui-se que os idosos apresentaram qualidade do sono ruim, sonolência diurna normal e qualidade de vida geral boa.

The objective of the study was to evaluate the quality of sleep and daytime sleepiness of a group of elderly people, checking whether there is an association with physical activity, presence of chronic disease, and Body Mass Index (BMI) and whether there is a correlation with BMI, age and quality of life. This is a cross-sectional and descriptive study. To assess sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used, the Epworth Sleepiness Scale (ESE) was used to assess daytime sleepiness, and the WHOQOL-BREF was used to assess quality of life. 47 elderly people were evaluated with a median (interquartile range 25-75%) of 66 (62-70) years of age and BMI of 28.58 (26.21-30.44). 74.5% had poor sleep, 61.7% had Normal Daytime Sleepiness and 97.8% classified as having a good quality of life, with emphasis on the domains of social relationships (80%) and self-assessment of quality of life (80%). There was only a statistically significant association between the presence of poor sleep quality and the practice of physical activity. There was no association between the presence of poor sleep quality or sleepiness with BMI and the presence of chronic disease. There was a weak, negative and statistically significant correlation only between sleep quality and quality of life (ρ=-0.466) and age (ρ=- 0.297). It is concluded that the elderly had poor sleep quality, normal daytime sleepiness and good general quality of life.

Fadiga e sono em trabalhadores de enfermagem intensivistas na pandemia COVID-19 / Fatigue and sleep in intensive care nursing workers in the COVID-19 pandemic

Resumo Objetivo Analisar a relação entre fadiga, qualidade do sono, variáveis de saúde e laborais em trabalhadores de enfermagem de terapias intensivas, na pandemia COVID-19. Métodos Estudo transversal, correlacional, realizado de julho de 2020 a fevereiro de 2021, com amostra aleatória e probabilística de enfermeiros e técnicos de enfermagem de hospitais universitários do Rio Grande do Sul, Brasil. Para a coleta de dados foi utilizado questionário sociodemográfico/ocupacional, Escala de Avaliação da Fadiga e Índice de Qualidade do Sono de Pittsburgh. Nas análises utilizaram-se teste Qui-Quadrado, teste U Mann-Whitney e coeficiente de correlação de Spearman, com nível de significância de 5%. Foi realizada análise de regressão binária logística. Resultados Participaram 114 trabalhadores, com prevalência de fadiga baixa e qualidade do sono ruim. A fadiga alta associou-se às variáveis ir trabalhar doente e perceber ruídos/vibrações como causa de desconforto. Técnicos de enfermagem associaram-se a qualidade do sono ruim e preocupação com a exposição a substâncias químicas. Fadiga e Qualidade do sono correlacionaram-se de forma moderada e direta. As análises ajustadas evidenciaram que enfermeiros e técnicos de enfermagem com fadiga alta apresentaram quatro vezes mais chances de terem qualidade do sono ruim (OR = 4,86; IC = 1,50-15,75). Conclusão A fadiga e qualidade do sono se correlacionaram de forma direta, e estão associados a fatores individuais e do trabalho. A fadiga alta aumentou as chances de ter pior avaliação da qualidade do sono. Estratégias institucionais e organizacionais devem ser revistas a fim de priorizar a proteção da saúde destes trabalhadores de enfermagem.

Resumen Objetivo Analizar la relación entre fatiga, calidad del sueño, variables de salud y laborales en trabajadores de enfermería de terapias intensivas, durante la pandemia de COVID-19. Métodos Estudio transversal, correlacional, realizado de julio de 2020 a febrero de 2021, con muestreo aleatorio y probabilístico de enfermeros y técnicos de enfermería de hospitales universitarios de Rio Grande do Sul, Brasil. Para la recopilación de datos se utilizó un cuestionario sociodemográfico/laboral, la Escala de Evaluación de Fatiga y el Índice de Calidad del Sueño de Pittsburgh. Para los análisis se utilizó la prueba χ2 de Pearson, la prueba U de Mann-Whitney y el coeficiente de correlación de Spearman, con un nivel de significación de 5 %. Se realizó el análisis de regresión binaria logística. Resultados Participaron 114 trabajadores, con prevalencia de fatiga baja y sueño de mala calidad. Se relacionó la fatiga con las variables ir a trabajar enfermo y percibir ruidos/vibraciones como causa de malestar. Se relacionó a los técnicos de enfermería con el sueño de mala calidad y la preocupación por la exposición a sustancias químicas. La fatiga y la calidad del sueño se correlacionaron de forma moderada y directa. Los análisis realizados evidenciaron que enfermeros y técnicos de enfermería con fatiga alta presentaron cuatro veces más probabilidades de tener sueño de mala calidad (OR = 4,86; IC = 1,50-15,75). Conclusión La fatiga y la calidad del sueño se correlacionan de forma directa y están relacionadas con factores individuales y del trabajo. La fatiga alta aumentó las probabilidades de tener una peor evaluación de la calidad del sueño. Las estrategias institucionales y organizacionales deben ser revisadas a fin de priorizar la protección de la salud de los trabajadores de enfermería.

Abstract Objective To analyze the relationship between fatigue, sleep quality, variables of health and work in intensive care nursing workers during the COVID-19 pandemic. Methods Cross-sectional, correlational study conducted from July 2020 to February 2021 with a random and probabilistic sample of nurses and nursing technicians from university hospitals in Rio Grande do Sul, Brazil. A sociodemographic/occupational questionnaire, the Fatigue Assessment Scale and the Pittsburgh Sleep Quality Index were used in data collection. The chi-square test, Mann-Whitney U test and the Spearman correlation coefficient were used in the analyzes, adopting a significance level of 5%. Binary logistic regression analysis was performed. Results Participation of 114 workers. There was prevalence of low fatigue and poor sleep quality. High fatigue was associated with the variables going to work sick and perceiving noise/vibrations as a cause of discomfort. Nursing technicians were associated with poor sleep quality and concern about exposure to chemical substances. Fatigue and sleep quality were moderately and directly correlated. Adjusted analyzes showed that nurses and nursing technicians with high fatigue were four times more likely to have poor sleep quality (OR = 4.86; CI = 1.50-15.75). Conclusion Fatigue and sleep quality were directly correlated and are associated with individual and work factors. High fatigue increased the chances of having worse sleep quality assessment. Institutional and organizational strategies should be reviewed in order to prioritize the health protection of these nursing workers.

Two distinct synchronization processes in the transition to sleep: a high-density electroencephalographic study.

OBJECTIVES: To assess how the characteristics of slow waves and spindles change in the falling-asleep process. DESIGN: Participants undergoing overnight high-density electroencephalographic recordings were awakened at 15- to 30-min intervals. One hundred forty-one falling-asleep periods were analyzed at the scalp and source level. SETTING: Sleep laboratory. PARTICIPANTS: Six healthy participants. INTERVENTIONS: Serial awakenings. RESULTS: The number and amplitude of slow waves followed two dissociated, intersecting courses during the transition to sleep: slow wave number increased slowly at the beginning and rapidly at the end of the falling-asleep period, whereas amplitude at first increased rapidly and then decreased linearly. Most slow waves occurring early in the transition to sleep had a large amplitude, a steep slope, involved broad regions of the cortex, predominated over frontomedial regions, and preferentially originated from the sensorimotor and the posteromedial parietal cortex. Most slow waves occurring later had a smaller amplitude and slope, involved more circumscribed parts of the cortex, and had more evenly distributed origins. Spindles were initially sparse, fast, and involved few cortical regions, then became more numerous and slower, and involved more areas. CONCLUSIONS: Our results provide evidence for two types of slow waves, which follow dissociated temporal courses in the transition to sleep and have distinct cortical origins and distributions. We hypothesize that these two types of slow waves result from two distinct synchronization processes: (1) a "bottom-up," subcorticocortical, arousal system-dependent process that predominates in the early phase and leads to type I slow waves, and (2) a "horizontal," corticocortical synchronization process that predominates in the late phase and leads to type II slow waves. The dissociation between these two synchronization processes in time and space suggests that they may be differentially affected by experimental manipulations and sleep disorders.

Sleep quality and OPRM1 polymorphisms: a cross-sectional study among opioid-naive individuals

ABSTRACT O sistema opioidérgico envolve a regulação do sono e da vigília. É possível, portanto, que os polimorfismos genéticos no OPRM1 influenciem na qualidade do sono. Este estudo investigou a associação de polimorfismos do OPRM1 com a qualidade subjetiva do sono entre indivíduos sem tratamento prévio com opióides. Este estudo observacional de corte transversal envolveu 161 homens que nunca haviam se tornado opióides (média de idade = 27,74 anos; variação: 18 a 63 anos). A qualidade subjetiva do sono foi avaliada com a versão traduzida e validada em malaio do Índice de Qualidade do Sono de Pittsburgh (PSQI). O DNA foi extraído do sangue total e submetido à reação em cadeia da polimerase (PCR) para dois polimorfismos OPRM1 (118A> G e IVS2 + 691G> C). Sujeitos combinados com 118A e IVS2 + 691Galelos (haplótipo AC) apresentaram escores significativamente mais baixos do PSQI [média (DP) = 4,29 (1,76)] em comparação àqueles sem o haplótipo [4,99 (2,50)] (p = 0,004). Por outro lado, os indivíduos com genótipo heterozigótico combinado (GC / AG diplotipo) apresentaram escores significativamente mais altos do PSQI em comparação àqueles sem o diplótipo [6,04 (2,48) vs 4,54 (2,22), p = 0,004]. Em indivíduos sem tratamento prévio com opiáceos, o haplótipo AC e o diplótipo GC / AG para os polimorfismos 118A> G e IVS2 + 691G> C do OPRM1 estão associados a uma melhor e pior qualidade do sono, respectivamente.