Somatic genetics analysis of sleep in adult mice

The molecular mechanisms of mammalian sleep regulation remain largely unknown. Classical forward and reverse mouse genetic approaches require germline mutations and, thus, are unwieldy to study the sleep functions of essential genes or redundant pathways. It is also costly and time-consuming to conduct large-scale electroencephalogram (EEG)/electromyogram (EMG)-based mouse sleep screening due to lengthy genetic crosses and labor-intensive surgeries. Here, we develop a highly efficient adult brain chimeric (ABC) expression/knockout (KO) platform and a highly accurate AI-augmented SleepV (video) system for high-througphut somatic genetics analysis of sleep in adult mice. This ABC platform involves intravenous administration of adeno-associated viruses (AAV) that bypass the blood brain barrier and transduce the majority of adult brain neurons. Constitutive or inducible ABC-expression of CREB and CRTC1 reduces both quantity and quality of non-rapid-eye-movement sleep (NREMS), whereas ABC-KO of CREB by AAV-mediated Cre/loxP recombination increases daily NREMS amount. Moreover, ABC-KO of exon 13 of Sik3 by AAV-Cre injection of Sik3-E13flox/flox adult mice phenocopies Sleepy (Sik3Slp/Slp) mice, which carry a germline splicing mutation resulting in skipping of exon 13 of Sik3. While both long and short isoforms of SLP kinase contribute to, ABC-KO of Slp allele by CRISPR/Cas9 rescues the hypersomnia of Sik3Slp/+ mice. Double ABC-KO of orexin/hypocretin receptors by CRISPR/Cas9 results in chocolate-induced narcolepsy episodes. We envision that these somatic genetics approaches should facilitate efficient and sophisticated studies of many brain-related cellular, physiological and behavioral processes in adult mice without genetic crosses.

588 Wake Up and Learn: A School Based Sleep Education and Surveillance Program

Introduction Insufficient sleep, especially for students, has been a hot topic in news for the past few years. However, despite this increase in media attention, the number of adolescents with unrecognized sleep difficulties continues to grow. A partnership between Janet Weis Children’s Hospital (Geisinger) and Montgomery School District was established to pilot a program called “Wake Up and Learn” (WUAL). WUAL is a population based preventative sleep screening and education program for 7th to 12th graders through an asynchronous virtual platform. This is a descriptive summary of implementation of WUAL and early phase results. Methods The WUAL team consists of a board-certified pediatric sleep specialist, school guidance counselor and 2 project managers. The Protection of Pupil Rights Amendment (PPRA) was considered. A letter describing the program with an opt-out option was provided. WUAL website was developed to serve as an educational resource and to access the surveys. The surveys were generated using REDcap and included the Epworth sleepiness scale -CHAD (ESS) and the childhood sleep habits questionnaire (CHSQ). The surveys became available online and the students were instructed access the website and complete the surveys as part of class time. Results A total of 289 surveys were accessed, 287 ESS (99%) and 281 CSHQ (97%) were completed. Pathologic ESS scores (> 9), suggesting excessive daytime sleepiness (EDS), was identified in 75 students (26%). Scores suggestive of sleep dysfunction (> 41) on the CSHQ was found in 184 students (65%). Out of the 184 students 64 students also had an abnormal ESS. Conclusion This method of screening has demonstrated a high degree of successful completion. Based on early data, sleep pathology may be more prevalent than typically reported in children (20–25%). EDS was common, present in a quarter of students. However, of 184 students with abnormal CHSQ only 35% also had EDS. This suggests that there may be a need to identify alternative daytime dysfunction, such as school performance or mental health symptoms. This is an ongoing program that will have further updates and plans for expansion to more school districts. Support (if any) Grant Funding Support from Jazz Pharmaceuticals and Janet Weis Children’s Hospital (Geisinger)

Exertional and nocturnal periodic breathing after successful cardiac transplantation. A case report

We present a case report of a heart failure patient who underwent cardiopulmonary exercise testing and sleep screening 12 months before and after heart transplantation (HTx). Severe Cheyne-Stokes respiration (CSR) with central sleep apnoea (CSA) was identified either before and after HTx, while periodic breathing during exercise vanished. We suggest that optimization of hemodynamics and medical therapy (low dose of diuretic) did not withdraw the central mechanisms underlying the diathesis for CSR-CSA. While periodic breathing during exercise reversal may support a closer link with an exertional central hemodynamic. This observation indirectly neglects the possible unifying mechanistic background of CSR and periodic breathing, during exercise, in this setting.

Sleep, Mild Cognitive Impairment, and Interventions for Sleep Improvement: An Integrative Review

Sleep disturbance in mild cognitive impairment (MCI) is associated with progression to Alzheimer’s disease (AD), more severe AD symptoms, and worse health outcomes. The aim of this review was to examine the relationship between sleep and MCI, and the effectiveness of sleep improvement interventions for older adults with MCI or AD. An integrative review was conducted using four databases, and findings were analyzed using an iterative process. Findings from 24 studies showed that alterations in sleep increased the risk of MCI and that the sleep quality of individuals with MCI or AD was poorer than healthy controls. Changes in brain anatomy were also observed in healthy older adults with sleep disturbances. Examined interventions were shown to be effective in improving sleep. Screening for sleep disturbances in individuals with MCI/AD is crucial to mitigate neurodegenerative or neurobehavioral risks in this population.

Application accuracy of the sleep decision tree to standardized patient cases by physiotherapists: an observational study

BackgroundPhysiotherapists assess lifestyle factors, including sleep health, that contribute to poor health outcomes. Recommendations of sleep screening assessments have been provided; however, physical therapists’ ability to successfully identify which patients would benefit from additional consultation has not been established.ObjectiveTo determine if physiotherapists can accurately apply an evidence-based sleep decision tree to four hypothetical standardized patient cases.MethodsParticipants applied the sleep decision tree to the four standardized cases via an online platform. Likert scales were used to assess perception of ease of use, likelihood of use, and how helpful they thought the sleep decision tree would be. Descriptive analyses and multiple linear regression models were conducted.ResultsEighty-eight individuals participated in the study. Eighty-one respondents (92%) correctly answered the least complex case while 12 (14%) correctly answered the most complex case. Seventy-four (84%) respondents indicated the sleep decision tree was easy to use, 57 (65%) answered they were likely to use the sleep decision tree in clinical practice, and 66 (75%) said the sleep decision tree would be helpful to their clients.ConclusionsPhysiotherapists were able to accurately apply a sleep decision tree to simpler patient cases but were frequently unable to apply it to more complex patient cases. This may be due to lack of education, perceived ease of using, and relevance of the sleep decision tree to their clinical practice. The sleep decision tree may aid physiotherapists in assessing sleep health, screening for sleep disturbances, and referring for further assessment.

Validation francophone des questionnaires de sommeil auprès des étudiants-athlètes du Québec

La création de l’Athlete Sleep Screening Questionnaire (ASSQ) et de l’Athlete Sleep Behavior Questionnaire (ASBQ) a répondu au besoin d’outils fiables et valides pour l’évaluation subjective du sommeil auprès des athlètes. Cependant, seule la version anglophone de l’ASSQ et de l’ASBQ a été validée. Cette étude a donc pour but de valider la version francophone de ces deux questionnaires afin de les rendre accessibles aux athlètes francophones du Québec. Deux cent trois étudiants-athlètes du Québec (18-30 ans) ont participé à l’étude impliquant de remplir deux séries de questionnaires et un agenda de sommeil dans un intervalle de sept jours. Les résultats indiquent une stabilité temporelle (r = .73) acceptable et une cohérence interne faible (α = .56-.62) pour l’ASSQ. Le score de difficulté de sommeil (SDS) de l’ASSQ au temps 1 se caractérise par une sensibilité de 85% et une spécificité de 88% comparativement à 67% et 92% au temps 2. Quant à l’ASBQ, il se caractérise par une stabilité temporelle (r =.73) et une cohérence interne (α = .68-.72) acceptable. L’ASBQ et l’ASSQ ont des propriétés psychométriques acceptables dans un contexte non-clinique et de dépistage. Une retraduction de certains items améliorerait les propriétés psychométriques de ces deux outils francophones.