bluuebunny/crossref_metadata_2025_split huggingface dataset:
0280 Orexins play a dual role in immobility episodes on taiep rats a model of H-ABC
Authors: Cortes Carmen , Espinoza Karely , De Ovando Carlos , Hernandez Hugo , Piazza Valeria 
Published: May 2022

Abstract

Introduction
Leukodystrophies are a heterogenous group of congenital myelin alterations with more than 30 classified diseases was described until now. Among them there are several mutations in the a and b tubulins the so called tubulinophaties, that affect the central nervous system. The hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is due to a mutation in the tubulin b 4a (TUBB4A) and the taiep rats is the only available model of this human disease with similar magnetic resonance changes and a punctual mutation in the TUBB4A. Taiep rats had immobility episodes (IEs) with a peak between at 9 months of age. Importantly, electroencephalographic recordings shown that IEs had a rapid eye movement (REM) sleep characteristic pattern supporting that are equal to human cataplexy episodes that are key sign of narcolepsy. It is possible to induced IEs when taiep rats are manipulated from the tail or the thorax. Narcolepsy in humans and narcoleptic dogs had a significant decreased in orexin levels in the cerebrospinal fluid (CSF) and a concomitantly decreased of orexin neurons in the lateral hypothalamus.

Methods
We used 21 male rats from taiep at 9 months of age. All rats were kept in standard conditions and were implanted for EEG, EMG and EOG recordings to characterize IEs. We administered orexin A and B agonists and characterized the sleep-wake cycle and frequency of IEs, the peptides were administered by a intracerebroventricular (i.c.v.) injections diluted in artificial CSF. We also measured the number or positive orexin neurons in the lateral hypothalamus through immunohistochemistry.

Results
The i.c.v. administration of [Ala11, D-Leu 15] orexin B agonist significantly decrease the frequency of IEs with 3 and 10 nM doses (P≤0.05 and P≤0.03, respectively), without affecting the sleep-wake pattern. However, the i.c.v. administration of Orexin A (17-33) an agonist did not affect the sleep-wake pattern or the frequency of IEs. It is relevant that the number of orexins neurons did not differ between taiep and control Sprague-Dawley (SD) male rats.

Conclusion
Our results showed that IEs had a REM sleep EEG characteristic pattern with cataplexic-like atonia, there are sensible to orexin B agonist, but the number of orexin positive neurons do not differ with respect to SD male rats. In conclusion taiep rats a model of H-ABC is an adequate model of cataplexy-like episodes due to myelin disease.

Support (If Any)
Partially supported by PRONACES-CONACYT grant 194171, and VIEP-BUAP 2021 to CA in Neuroendocrinología. KGE is fellowship from CONACYT No. 772626.
0282 Elevated levels of Extracellular Vesicle Cytokines are Associated with Poor Sleep Quality in Warfighters with Chronic Mild TBI
Authors: Guedes Vivian , Gottshall Jackie , Mithani Sara , Leete Jackie , Lai Chen , Gill Jessica , Kenney Kimbra , Werner Kent 
Published: May 2022

Abstract

Introduction
Sleep disorders are common in military populations and frequently occur comorbidly with mild traumatic brain injury (mTBI), resulting in substantial health risks. Although inflammation and cytokine elevations have independently been reported both after traumatic brain injury (mTBI) and in association with sleep dysfunction, the impact of these factors on inflammatory processes in a combined context (i.e. post-mTBI sleep dysfunction) has yet to be explored. Extracellular vesicles (EVs) are a particularly promising source of these cytokines; EVs are lipid bilayer-enclosed particles released by cells to the extracellular environment, constituting a newly discovered form of cell-to-cell communication that may afford improved signal-to-noise ratio and more functionally specific protein biomarkers than free (soluble) sources. To determine whether mTBI and sleep dysfunction may bidirectionally regulate inflammatory processes, the present study examined associations between plasma and EV levels of cytokines and sleep quality in a cohort of warfighters with and without chronic mTBI.

Methods
Participants (n=182) were enrolled in the Chronic Effects of Neurotrauma Consortium (CENC) Multicenter Prospective Longitudinal Study/ Long-Term Impact of Military Brain Injury Consortium (LIMBIC). They were divided into control (no TBI history) or mTBI groups (positive history of mTBI). EV and plasma levels of interleukin (IL)-10, IL-6, and tumor necrosis factor-alpha (TNFα) were analyzed using a Simoa HD-1 analyzer. Sleep quality was evaluated using Pittsburgh Sleep Quality Index (PSQI).

Results
Within the mTBI group, patients reporting poor sleep quality (PSQI ≥10) had elevated EV levels of IL-10 (ß(SE) = 0.12(0.04), p&lt;0.01) when compared to those reporting good sleep (PSQI&lt;10). Sleep quality was associated with EV levels of IL-10 (ß(SE)=0.11(0.04), p=0.01) and TNFα (ß(SE)=0.07(0.03), p&lt; 0.01) in mTBI patients. Plasma levels of cytokines were not significantly associated with sleep quality.

Conclusion
Our findings suggest that EV levels of IL-10 and TNFα, but not their plasma levels, are associated with self-reported sleep quality warfighters with history of mTBI. Our results suggest that EVs are relevant signaling mechanisms in sleep-related inflammatory responses following mTBI. Larger prospective studies are needed to further investigate the links between EV cytokines and sleep quality in participants with mTBI.

Support (If Any)
This work was supported by grant funding from: Department of Defense, Chronic Effects of Neurotrauma Consortium (CENC) Award W81XWH-13-2-0095 and Department of Veterans Affairs CENC Award I01 CX001135.
0284 Repetitive Weekly REM Sleep Deprivation-Recovery Cycle Obtained from a Large U.S. Sample by Home-Based Under-Mattress Monitoring Devices
Authors: Kushida Clete , Cotton-Clay Andrew , Baron Susan , Fava Laura , Easwar Venkat , Kinsolving Arthur , Kahn Philippe , Zitser Jennifer , Rama Anil , Ding Feihong 
Published: May 2022

Abstract

Introduction
American adults are typically sleep deprived during weekdays and attempt to recover sleep on the weekends. Technological advances in home sleep monitoring have provided the opportunity to analyze sleep patterns on a scale much larger than previously imaginable. This study explores the weekly REM sleep deprivation–recovery cycle in a large U.S. sample.

Methods
Estimated total sleep time (TST) and REM/TST (R%) were analyzed by a commercially-available home-sleep-monitoring device (Sleeptracker-AI Monitor, Fullpower Technologies, California, USA). The device passively monitors sleep using piezo-electric sensors that register the forces exerted through the mattress. The de-identified data from the devices were analyzed following review and exemption of the study (#57681) from the Stanford University IRB. Data from 07/2020–06/2021, from 101,442 individuals with 14,277,964 recorded nights, were available. The analytic dataset included individuals with at least 300 nights of sleep per year and 26 of 52 nights per each day of the week (excluding nights abutting federal holidays).

Results
A total of 21,543 individuals (11,095 men, 51±14 years; 9,821 women, 50±15 years; 627 unspecified genders) and 6,850,717 recorded nights met the inclusion criteria. There is a stepwise increase in R% from Sunday night to Friday night and a decrease back to Sunday night, following a cycle of weekday sleep deprivation and weekend recovery. The means and standard deviations (across individuals’ averages) of TST in hours and R% for each night were: Sunday (TST*:7.21±0.885, R%*:24.20±3.09), Monday (TST*:7.18±0.853, R%*:24.56±3.10), Tuesday (TST*:7.16±0.847, R%*:24.67±3.13), Wednesday (TST*:7.16±0.845, R%*:24.80±3.15), Thursday (TST*:7.18±0.845, R%*:24.87±3.15), Friday (TST*:7.51±0.904, R%*:25.05±3.15), and Saturday (TST*:7.59±0.897, R%*:24.83±3.12). Each statistic, when compared with the previous night of the week, was significant (p &lt; 0.05/7, Bonferroni corrected) by paired t-test (denoted by an asterisk).

Conclusion
The use of advanced technology to estimate sleep-wake patterns in a large sample permits the validation of a repetitive REM sleep deprivation–recovery cycle. Individuals are, on average, partially sleep deprived starting Sunday night, which leads to a progressive REM sleep rebound that transitions into a REM recovery cycle on Friday and Saturday nights. Further work will focus on studying this cycle within different groups (e.g., age, gender), across seasons, and including other sleep parameters.

Support (If Any)
0285 Excessive daytime sleepiness with long sleep duration increases myocardial infarction risk
Authors: Wang Heming , Sofer Tamar , Saxena Richa , Purcell Shaun , Huang Tianyi , Zhu Xiaofeng , Rutter Martin , Redline Susan 
Published: May 2022

Abstract

Introduction
Excessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with cardiovascular diseases (CVD) and mortality. However, EDS is heterogeneous, associated with both short and long sleep duration. It is unclear whether each subtype is related to CVD.

Methods
To understand the association of EDS subtypes (stratified by sleep duration) with incident myocardial infarction (MI), we perform multivariable Cox proportional hazards regression on MI using longitudinal medical record data of 471,991 individuals free of CVD at baseline from the UK Biobank. Baseline EDS and sleep duration were assessed by self-reported questionnaires.

Results
After adjusting for multiple social-demographic and behavioral factors, EDS with long sleep (³9 hours) was associated with a 91% increased incidence of MI (HR=1.91, 95% CI 1.34-2.71) compared to healthy sleep pattern (sleeping 6-9 hours without sleepiness), while EDS with normal (6-9 hours) or short sleep (≤6 hours) was not associated with incident MI. Long sleep without sleepiness was associated with a 39% increase in incident MI (HR=1.39, 95% CI 1.14-1.71). The association of EDS with long sleep was not explained by chronotype, insomnia, sleep apnea, depression, hypertension, or type 2 diabetes, but was confounded with self-reported overall health conditions (HR=1.46, 95% CI 1.02-2.08 after adjustment).

Conclusion
Our study suggests the previous association evidence of EDS increasing risk of MI may be primarily driven by its long sleep subtype (high “sleep propensity”), but the underlying mechanisms are unclear. Future work is needed to understand whether there are targetable interventions for this novel sleep phenotype that may improve cardiovascular health.

Support (If Any)
This research has been conducted using the UK Biobank Resource under Application Number 6818. Funding supports: NHLBI R35HL135818 and R01HL153814.
0286 Presence and Potential Impact of Demographically Based Attrition in Pediatric Sleep Manipulation Research
Authors: Beebe Dean , Rajput Gargi , Whitacre Catharine 
Published: May 2022

Abstract

Introduction
Pediatric sleep manipulation studies have mostly enrolled youth from dominant-culture, higher-income families. Studies with more diverse samples have been underpowered to detect differential attrition and demographic effect moderators. Here we pool data from two adolescent sleep manipulation protocols in a Midwest US city to better examine demographic differences in attrition rates and effect sizes.

Methods
Samples were pooled from studies detailed in Beebe et al. (2017; SLEEP, zsw035) and Duraccio et al. (2021; JSR, e13054). Both involved a sleep stabilization week, followed by 5-night periods of sleep restriction (6.5 hours/night in bed) and healthy sleep (9.5-10 hours/night in bed) in randomized counterbalanced order. Primary caregivers and 14-17 year-old adolescents each completed attention and sleepiness questionnaires for both conditions. Here we compare adolescents who were caregiver-identified as Black vs. White, the two largest local racial groups. Caregivers also reported their own education, family income, and household structure (single- vs. two-parent). Non-parametric tests looked for differential attrition and MANCOVA tested for racial differences in effects.

Results
Of the 257 initially enrolled, Black adolescents and those from households with one parent, lower income, or lower caregiver education were differentially lost to attrition (all p&lt;.001), even though the racial makeup of the final sample approximated the regional population (36% Black, 64% White). In the final sample, Black and White youth were equally able to change their sleep (p&gt;.90). Manipulation effects were significantly smaller for Black than White adolescents for inattention (self-report p=.026; parent-report p=.017) and sleepiness (self-report p=.002, parent-report p&lt;.001), but these differential effects were non-significant after controlling for family income, household structure, and caregiver education (p&gt;.05).

Conclusion
Even when a final study sample seemingly approximates the diversity of the local population, differential attrition may affect results. In this case, it superficially appeared that being in a non-dominant group (self-identified Black) was protective against the impact of short sleep. However, this effect disappeared after controlling for demographic risk factors. Participation in sleep manipulation studies can be challenging, so families facing higher burdens may need more support; otherwise, only the most resilient of those families may succeed, which could distort findings.

Support (If Any)
NIH (R01HL120879, R01HL092149)
0287 Effects of Sleep Restriction and Recovery on the Capacity of Glucocorticoids to Inhibit Inflammatory Marker Expression in Human Monocytes
Authors: Engert Larissa , Eske Annika , Buraks Olivia , Dang Rammy , Mullington Janet , Haack Monika 
Published: May 2022

Abstract

Introduction
Chronic low-grade systemic inflammation is involved in the pathogenesis of many human diseases. Common sleep patterns of restricting sleep during weekdays and catching up on sleep over the weekend induce inflammatory upregulation that may not resolve following weekend recovery sleep. We hypothesize that this sleep pattern leads to an inflammatory imbalance of markers regulating inflammatory homeostasis, including inflammatory markers (eg, interleukin-6 (IL-6) and cyclooxygenase 2 (COX-2)) and markers of counter-inflammation (eg, glucocorticoids (GCs)). The enzyme COX-2 is involved in prostaglandin synthesis and is the target of pain-relieving nonsteroidal anti-inflammatory drugs (NSAIDs). GCs are used in the treatment of many inflammatory diseases, including severe acute infection with SARS-CoV-2. We investigated if sleep restriction impairs the capacity of GCs to inhibit inflammatory COX-2 expression in a preliminary dataset.

Methods
The present preliminary dataset (N=6, 2F/4M) derives from an ongoing randomized controlled within-subjects trial consisting of three 11-day in-hospital protocols (2 restricted sleep arms, 1 control sleep arm). The ongoing study is blinded for administration of placebo or aspirin under sleep restriction. Under restricted sleep conditions, 2 nights of baseline sleep (8h/night) were followed by 5 nights of restricted sleep (4h/night), concluding with 3 nights of recovery sleep (8h/night). In the control condition, participants could sleep 8h/night throughout the entire protocol. Blood samples were taken after baseline sleep, after 5 nights of restricted or control sleep, and after 2 nights of recovery sleep. Data were analyzed using generalized linear mixed models.

Results
Sleep restriction was associated with decreased capacity of GCs to inhibit COX-2 expression in monocytes (p&lt;.01) and has the expected inflammatory effect on IL-6 production in monocytes (p&lt;.01). Moreover, sleep restriction has lasting inflammatory effects as shown in increased inflammation following 2 nights of recovery sleep (p&lt;.01).

Conclusion
In conclusion, the present preliminary analysis suggests that in patients treated with GCs, sleep restriction potentially reduces their effectiveness in controlling inflammation, thus contributing to increased inflammation-related morbidity. Sample collection and data analysis is ongoing.

Support (If Any)
NIH/NHLBI R01-HL136310; NIH/NCRR UL1-RR02758, M01-RR01032; German Research Foundation (DFG) EN1291/1-1.
0288 Role of cofilin and calcium signaling in sleep-loss neural injury
Authors: Chou Allison Tzu-Han , Hollis Henry , Fenik Polina , Pullum Keelee , Slinger Michelle , Zamore Zachary , Zhu Yan , Anafi Ron , Veasey Sigrid 
Published: May 2022

Abstract

Introduction
Chronic sleep disruption (CSD) in young adult mice leads to phenotypes consistent with early (pre-plaque) Alzheimer’s Disease (AD), including increased Aβ and hippocampal neuron loss. Mechanisms underlying this injury are not known. Both acute sleep loss and AD activate cofilin, a regulator of actin dynamics. Activated cofilin (AC) in AD mouse models can impart neural injury, increase Aβ, and cofilin translocation to the mitochondria delays cytosolic Ca2+ clearance. We are critically testing the role of AC in chronic short sleep (CSS) and sleep fragmentation (SF) neural injury.

Methods
Synapse loss was studied using STED confocal microscopy and Imaris in CSS (n=9) and rested (n=10) mice. Synapses were identified as overlaps of pre- and postsynaptic densities. Percent area of cofilin was measured with FIJI. To further understand if and how wake-induced cofilin activation induces sleep-loss synapse and neural injury, we implanted AAV9CAMKII-GCaMP6f and then GRIN lenses, and later studied CAMKII calcium transients in CA1 of WT controls (n=4) and SF mice (n=4) by measuring GCaMP6f calcium transients. We developed a Shiny R application to analyze the frequency of Ca2+ spikes, ΔF/F0, and the rising and clearance patterns of spikes. To directly test cofilin’s role in delayed calcium clearance, we studied the calcium transients in hAPP mice (n=2) after injection of AAV-CAMKII-CofilinS3A to express AC and GCaMP6f. All data were analyzed with two-way ANOVA or unpaired t-tests.

Results
Results reveal significant synapse loss in CA1 of CSS mice (CSS=48.8±10.3; Rested=83.4±8.4), t(16)=2.63, p&lt;0.02, and increased cofilin activation (AC=19.8±3.41; Rested=8.76±1.95), t(16)=8.43, p&lt;0.0001. SF mice reveal an increase in NREM sleep firing rates, F(1,1)=22.0, p&lt;0.001. In contrast, hAPP-AC mice show significantly increased ΔF/F0, F(1,1)=356, p&lt;0.0001, prolonged calcium influx, F(1,1)=18.6, p&lt;0.02, and prolonged calcium clearance duration, F(1,1)=23.9, p&lt;0.01, but not increased firing frequencies.

Conclusion
CSS induces CA1 synapse loss and cofilin activation in WT mice. Increased CAMKII calcium ΔF/F0 occurs through different pathways in SF and AC, suggesting additional factors in CSD neural injury.

Support (If Any)
NIH AG054104; AG064231
0290 Associations between sleep duration and sedentary behavior in healthy, young adults
Authors: Melanson Edward , Depner Christopher , Wright Kenneth , Creasy Seth , Kubicki Michelle , Zimmerman Grace 
Published: May 2022

Abstract

Introduction
Chronic diseases are more prevalent among populations with greater daily sedentary time and among populations with insufficient sleep duration. Yet, little is known about the potential links between insufficient sleep and sedentary behavior. Early findings from recent studies show variable and bidirectional associations between sleep duration and sedentary behavior, based on the population studied. The purpose of this investigation was to measure associations between: (1) sleep duration and sedentary time the next day; and (2) sedentary time and sleep duration the same study day/night, during a sleep extension intervention.

Methods
Data collection are ongoing. To date, three participants (2 female; aged 24.7±4.04yr; BMI 21.73±2.38kg/m2) with self-reported habitual insufficient sleep (&lt;6.5h per night) completed the study protocol in its entirety. Sedentary behavior (&lt;1.5 METs, in seated or lying posture) and sleep duration were measured via activPALTM and wrist-actigraphy, respectively, at baseline for days 1-13. After baseline, participants completed a sleep extension intervention for study days 15-41, with sedentary behavior and sleep duration measured during study days 28-41. Only study days with full 24h activPAL™ wear time were included in statistical analyses. Associations between sedentary behavior and nightly sleep duration were analyzed by linear mixed-model regression. We focused this preliminary analysis of 3 participants on R2.

Results
Sleep duration was significantly increased (p&lt;0.05) during sleep extension (7.6±1.5h) versus baseline (7.0±1.4h). Sedentary behavior was not significantly different (p=0.869) during sleep extension (8.4±1.6h) versus baseline (8.3±2.0h). The association between sleep duration to sedentary time the following day had p=0.683, R2=0.51, and =2.5±6.2h. The association between daily sedentary time to sleep duration the same study day/night had p=0.72, R2=0.12, and =2.3±6.2h.

Conclusion
Preliminary findings from 3 participants in this ongoing study suggest that sleep extension is not associated with changes in sedentary behavior.

Support (If Any)
NIH-UL1TR002535, NIH-K01HL145099, Colorado Clinical Translational Science Institute Pilot (CO-J-20-119), University of Utah Seed Grant-10060570
0291 Social Desirability Mediates Self-Reported Sleepiness during a Laboratory Total Sleep Deprivation Study
Authors: Scott Jonah , Muck Rachael , Van Dongen Hans , Honn Kimberly 
Published: May 2022

Abstract

Introduction
Total sleep deprivation (TSD) increases sleepiness and impairs vigilant attention. There are large individual differences in vulnerability to sleep loss, but individuals’ self-ratings of sleepiness often do not align with their objective performance impairment. Here we investigated whether the trait of social desirability – the desire to conform to social standards – plays a role.

Methods
N=39 healthy adults (ages 27.6±4.6y; 22 men) completed a 3-night/4-day in-laboratory study with 10h baseline and recovery sleep opportunities (22:00–08:00) preceding and following a 38h period of TSD. Every 2–4h during TSD, subjects completed the Karolinska Sleepiness Scale (KSS) and a 10min Psychomotor Vigilance Test (PVT) to assess subjective sleepiness and vigilant attention, respectively. Throughout the study, subjects were behaviorally monitored by the researchers. Prior to the study, subjects completed the Marlow-Crowne Social Desirability (MCSD) scale. Based on standard criteria, subjects were categorized post hoc into average (n=13) and high (n=26) social desirability groups (no subjects in the sample scored low on social desirability). Self-reported sleepiness scored on the KSS and lapses (reaction times ≥500ms) on the PVT were analyzed using mixed-effects ANOVA with fixed effects for time awake and MCSD group and their interaction.

Results
As expected, there was a main effect of time awake for KSS score (F[12,441]=31.48, p&lt;0.001) and PVT lapses (F[12,441]=16.27, p&lt;0.001), with sleepiness and lapses increasing during TSD. We found a main effect of MCSD group for KSS score (F[1,441]=4.56, p=0.033), with the high MCSD group reporting lower levels of sleepiness than the average MCSD group. However, there was no effect of MCSD group for PVT lapses (p=0.93) and no time awake by MCSD interaction for either KSS (p=0.86) or PVT (p=0.99).

Conclusion
Subjects high in social desirability reported less sleepiness during TSD than those with average social desirability yet their objective performance was equally degraded. This finding has implications for fatigue risk management because individuals with high social desirability may underreport their sleepiness. This may undermine the reliability of self-report assessments of sleepiness and ability to work safely. [ 1] Whether there is bias in self-reported sleepiness for individuals low in social desirability as well remains to be investigated.

Support (If Any)
Support: ONR N00014-13-1-0302 and PRMRP W81XWH-20-1-0442