bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of Limb and Epaxial Muscle Activity During Walking in the Fire Salamander,Salamandra salamandra
Authors: Pierce S E , Lamas L P , Pelligand L , Schilling N , Hutchinson J R
Published: May 2020

Synopsis

Salamanders and newts (urodeles) are often used as a model system to elucidate the evolution of tetrapod locomotion. Studies range from detailed descriptions of musculoskeletal anatomy and segment kinematics, to bone loading mechanics and inferring central pattern generators. A further area of interest has been in vivo muscle activity patterns, measured through electromyography (EMG). However, most prior EMG work has primarily focused on muscles of the forelimb or hindlimb in specific species or the axial system in others. Here we present data on forelimb, hindlimb, and epaxial muscle activity patterns in one species, Salamandra salamandra, during steady state walking. The data are calibrated to limb stride cycle events (stance phase, swing phase), allowing direct comparisons to homologous muscle activation patterns recorded for other walking tetrapods (e.g., lizards, alligators, turtles, mammals). Results demonstrate that Salamandra has similar walking kinematics and muscle activity patterns to other urodele species, but that interspecies variation does exist. In the forelimb, both the m. dorsalis scapulae and m. latissimus dorsi are active for 80% of the forelimb swing phase, while the m. anconaeus humeralis lateralis is active at the swing–stance phase transition and continues through 86% of the stance phase. In the hindlimb, both the m. puboischiofemoralis internus and m. extensor iliotibialis anterior are active for 30% of the hindlimb swing phase, while the m. caudofemoralis is active 65% through the swing phase and remains active for most of the stance phase. With respect to the axial system, both the anterior and posterior m. dorsalis trunci display two activation bursts, a pattern consistent with stabilization and rotation of the pectoral and pelvic girdles. In support of previous assertions, comparison of Salamandra muscle activity timings to other walking tetrapods revealed broad-scale similarities, potentially indicating conservation of some aspects of neuromuscular function across tetrapods. Our data provide the foundation for building and testing dynamic simulations of fire salamander locomotor biomechanics to better understand musculoskeletal function. They could also be applied to future musculoskeletal simulations of extinct species to explore the evolution of tetrapod locomotion across deep-time.
Determination of Free and Total Choline and Free and Total Carnitine in Infant Formula and Adult/Pediatric Nutritional Formula by Liquid Chromatography/Tandem Mass Spectrometry (HPLC-MS/MS): A Multi-laboratory Testing Study, Final Action 2015.10
Authors: Shippar Jeffrey , Ellingson David , Sabbatini Jane
Published: May 2020

Background

A multi-laboratory study was conducted on AOAC First Action Method 2015.10 “Determination of Free and Total Choline and Free and Total Carnitine in Infant Formula and Adult/Pediatric Nutritional Formula by Liquid Chromatography/Tandem Mass Spectrometry (HPLC-MS/MS).”

Objective

In this study, nine laboratories participated in the performance testing of the method using ten nutritional products tested as blind duplicates.

Method

Both free and total carnitine and free and total choline content of the samples were determined using separate extractions for the free and total results. For free choline and carnitine analysis, samples are diluted in water. For total choline and carnitine analysis, samples are extracted using acid-assisted microwave hydrolysis with nitric acid. For both the free and total methods, samples are then diluted with acetonitrile and analyzed using strong cation exchange (SCX) liquid chromatography coupled to a triple quadrupole tandem mass spectrometer (LCMS). Stable isotope labeled internal standards were utilized in all analyses to compensate for extraction inefficiencies and ionization suppression.
COVID-19 immunity certificates: science, ethics, policy, and law
Authors: Greely Henry T
Published: May 2020

There is much discussion of adopting COVID-19 immunity certificates to allow those proven to have antibodies to the SARS-CoV-2 virus that causes COVID-19 to resume normal life and help restart the economy. This article points out issues that must be considered before adopting any such program. These issues fall into six categories: the uncertain science of COVID-19 immunity; the questionable quality of COVID-19 antibody tests; practical problems with issuing such certificates; deciding how the certificates might be used; ethical and social issues they would raise, especially fairness and self-infection; and potential legal barriers. It does not ultimately take a position on whether some narrow COVID-19 immunity plans should be adopted, concluding that the answer depends on too many currently unknown conditions. But its seventh part makes recommendations to decision-makers who might consider implementing such programs.
Characterization of G-CSF receptor expression in medulloblastoma
Authors: Paul Megan Rose , Huo Yuchen , Liu Andrea , Lesperance Jacqueline , Garancher Alexandra , Wechsler-Reya Robert J , Zage Peter E
Published: May 2020

Background

Identifying mechanisms of medulloblastoma recurrence is a key to improving patient survival, and targeting treatment-resistant subpopulations within tumors could reduce disease recurrence. Expression of the granulocyte colony-stimulating factor receptor (G-CSF-R, CD114) is a potential marker of cancer stem cells, and therefore we hypothesized that a subpopulation of medulloblastoma cells would also express CD114 and would demonstrate chemoresistance and responsiveness to G-CSF.

Methods

Prevalence of CD114-positive (CD114+) cells in medulloblastoma cell lines, patient-derived xenograft (PDX) tumors, and primary patient tumor samples were assessed by flow cytometry. Growth rates, chemoresistance, and responses to G-CSF of CD114+ and CD114-negative (CD114−) cells were characterized in vitro using continuous live cell imaging and flow cytometry. Gene expression profiles were compared between CD114+ and CD114− medulloblastoma cells using quantitative RT-PCR.

Results

CD114+ cells were identifiable in medulloblastoma cell lines, PDX tumors, and primary patient tumors and have slower growth rates than CD114− or mixed populations. G-CSF accelerates the growth of CD114+ cells, and CD114+ cells are more chemoresistant. The CD114+ population is enriched when G-CSF treatment follows chemotherapy. The CD114+ population also has higher expression of the CSF3R, NRP-1, TWIST1, and MYCN genes.

Conclusions

Our data demonstrate that a subpopulation of CD114+ medulloblastoma cells exists in cell lines and tumors, which may evade traditional chemotherapy and respond to exogenous G-CSF. These properties invite further investigation into the role of G-CSF in medulloblastoma therapy and methods to specifically target these cells.
Hamburg, 1350–1815
Authors: Hatje Frank
Published: May 2020

Originally, Hamburg was a borough around the cathedral of the archbishops of Hamburg-Bremen and a mercantile port city founded by the counts of Holsatia. In the 13th century both towns were united, given privileges supporting port and trade, and granted an ample political autonomy. As a member of the Hanseatic League, the city grew economically and demographically, particularly when Dutch and Sephardic refugees transferred their capital, know-how, and commercial networks after the fall of Antwerp in 1585. By that time, Hamburg’s merchants had already begun to link the markets around the Baltic and North Seas with the Iberian Peninsula and the Mediterranean. The extraordinary upturn around 1600 is evidenced by a rapid population growth and the huge sums that were spent on public buildings, which reflected Dutch influence, like the fortification and a number of welfare institutions as well as the stock exchange and the bank which turned Hamburg into an international hub of finance and trade ranking next to Amsterdam and London. During the 18th century her port became one of the most important emporia for French colonial goods until the 1790s, when the effects of the revolutionary wars made it crucial for British (re-)exportation to central Europe. The economic development was supported by Hamburg’s extraordinary constitutional setting. In 1618, the city’s status as a Free Imperial City was confirmed, whereas the kings of Denmark relinquished their claims on the city not until 1768, which resulted in strict neutrality policies of an independently acting city state whose rather exceptional republican constitution had been agreed upon by magistrate and citizens’ assembly in 1529, together with adopting the Reformation. Hamburg’s “state church” became a stronghold of orthodox Lutheranism. Since late 17th century, religious pluralism spread and Hamburg became one of the centers of the Enlightenment in the German-speaking lands, not least fostered by its republican political and civic culture. While the French revolution was hailed among the city’s elites, the effects of the French occupation in 1806 and the integration into the Napoleonic Empire in 1811 cooled down any enthusiasm. Although this nourished a considerable current of national patriotism, politics as well as civic identity resulted from the patriotic self-consciousness of a sovereign, independent city state trading with the rest of the world.
Glocalization
Authors: Roudometof Victor N.
Published: May 2020

Glocalization is a concept used in diverse fields of study, and the frequency of its use has increased significantly since 1995. Because its use ranges from geography to sociology to business studies to communication studies, this entry is interdisciplinary or transdisciplinary in nature and refers to work in other disciplines beyond the field of communication. Glocal and glocalization are neologisms that emerged in 1990–1991, resulting from merging the words local and global into a single word to indicate the fusion between the two. The Japanese idea of global localization is conventionally cited as the precursor concept behind the notion of glocal. There are several interpretations of glocalization in the literature, and this plurality illustrates both the heuristic value of the concept itself as well as the fact that its appropriation is often shaped by disciplinary blinders. In this entry, there are brief overviews of the theories or approaches to glocalization developed by Roland Robertson, Erik Swyngedouw, and Victor Roudometof, as well as the approaches aligned with the world society perspective. The topic of information and communication technology (ICT) and its relationship to glocalization is addressed separately to allow a more in-depth presentation of relevant research. The introduction of glocalization in social science research has also prompted a debate over the adoption of glocal methodologies. In addition, this entry features bibliographical surveys and a list of scholarly journals explicitly devoted to the study of glocalization. It should be noted that globalization and glocalization are related, as glocalization emerged after globalization’s emergence in the social-scientific debate. But the underlying notion of fusion or cultural hybridity is not new. Consequently, in this entry, discussion is focused specifically on glocalization as such and not on globalization, hybridity, or cultural fusion in general. Lastly, although Professor Tomiyuki Uesugi (Seijo University, Japan) has proposed the notion of “glocal studies,” to this date no such field exists.
0017 Transmembrane TNF- Soluble TNF Receptor Reverse Signal to Induce a Wake-Like State in Vitro
Authors: Dykstra-Aiello C J , Koh K , Nguyen J , Krueger J M
Published: May 2020

Introduction

Tumor necrosis factor (TNF) has sleep regulatory roles. Neuronal action potentials enhance TNF expression. Neuron/glia co-cultures exhibit more intense local sleep-like states after TNF administration in vitro. Both TNF and TNF receptors (Rs) are produced as transmembrane (tm) proteins that can subsequently be cleaved to produce soluble (s) forms. With immunocytes, sTNFR can bind tmTNF and induce reverse signaling within the cell expressing the tmTNF. This is opposite of conventional signaling induced by soluble ligands (e.g. sTNF) binding to transmembrane receptors. Having previously shown sleep inhibition after sTNFR administration in vivo, we hypothesized that tmTNF-sTNFR binding would induce wake-like states in vitro through reverse signaling.

Methods

Somatosensory cortical neurons/glia, from wildtype (WT) mice and mice lacking either TNF (TNF-KO) or both TNFRs (TNFR-KO), were co-cultured on multi-electrode arrays. Daily one-hour recordings were taken consecutively on incubation days 4 - 13 for development analyses. On day 14, a one-hour baseline was recorded prior to treatment with sTNFR (0.0 ng/μL-120 ng/μL). Immediately after treatment, recordings resumed for one hour. Synchronization of electrical activity (SYN), action potentials, slow wave power (SWP; 0.25–3.75 Hz), and burstiness index (measures used to define sleep in vivo) were used to characterize the ontological emergence of these electrophysiological properties and sTNFR-induced changes in vitro.

Results

Development rates were reduced in TNF-KO cells and increased in TNFR-KO cells relative to each other and to WT mice. Additionally, after sTNFR treatments, cells from TNFR-KO mice, which still express TNF, exhibited dose-dependent decreased SYN and SWP, indicative of a wake-like state. In contrast, cells from TNF-KO mice lacked a response to sTNFR treatment.

Conclusion

To our knowledge, this is the first demonstration of reverse TNF signaling with respect to sleep/wake states. As such, it provides a new way of viewing state regulation and associated potential clinical applications.

Support

This work was supported by grant NS096250 awarded to JK by NIH/NINDS.
0024 PTSD with Concurrent Excessive Daytime Sleepiness Alters Gene Expression in Military Personnel and Veterans; An RNA-Sequencing Study
Authors: Pattinson C L , Edwards K , Guedes V A , Mithani S , Yun S , Taylor P , Dunbar K , Lai C , Roy M J , Gill J M
Published: May 2020

Introduction

Up to 91% of military personnel and veterans with posttraumatic stress disorder (PTSD) report co-occurring sleep disturbances, including. insomnia and excessive daytime sleepiness (EDS). Sleep disturbances have been shown not only to increase the risk of developing PTSD, but to exacerbate and maintain PTSD symptomology. The aim of this study was to examine gene expression in active duty military personnel and veterans with PTSD, with and without EDS. Participants were categorized into three groups; 1) PTSD with EDS (PTSDwEDS; n=21), 2) PTSD without EDS (PTSDnoEDS; n=25), or 3) Controls (no PTSD and no EDS; n=57).

Methods

Participants were 79% male, mean age of 37.6years (SD=11.2years). PTSD symptoms were measured using the PTSD checklist for civilians (PCL-C); participants were classified as PTSD-present using DSM-IV-TR criteria of “moderate-to-severe”. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS), high sleepiness was indicated by an ESS score >13. We performed RNA-seq with Illumina’s HiSeq 2500 in paired-end. We conducted quality control using FastQC and aligned to GRCh38 reference genome using STAR (v2.5.3a). Differentially expressed genes identified using DESeq2 (v1.20.0) with False Discovery Rate of 0.10. Finally, Ingenuity Pathway Analysis (IPA) was conducted to identify dysregulated gene networks.

Results

Between the Controls and PTSDnoEDS groups, two genes were significantly dysregulated. In controls and PTSDwEDS groups, 251 genes were dysregulated. The IPA networks showed that genes associated with inflammation were significantly dysregulated. Finally, between PTSDwEDS and PTSDnoEDS there were 1,873 significantly dysregulated genes. The IPA networks identified dysregulation of genes related to sleep, fatigue, circadian, and mitochondrial function.

Conclusion

Taken together this data indicates that EDS that is co-morbidly experienced with PTSD is associated with significant gene dysregulation, above and beyond that observed in participants with PTSD without significant EDS and controls. Treating EDS in military personnel and veterans with PTSD is important.

Support

This work was supported by the Center for Neuroscience and Regenerative Medicine (CNRM)
0030 Effect of a Simulated Sunset versus Typical Indoor Lighting on Evening Melatonin Levels
Authors: Lanza S M , Kindel B C , Sprecher K E , Trainer M M , Wright K P
Published: May 2020

Introduction

The human circadian clock evolved in the presence of the natural light-dark solar cycle. Exposure to artificial light at night suppresses endogenous melatonin levels and delays the timing of the circadian clock. The advent of tunable LED (light emitting diode) technology presents an opportunity to develop and implement circadian based practices for healthy lighting. Here we determined the influence of a simulated sunset with tunable LED technology on evening melatonin levels.

Methods

Nine healthy adults (3 females, 24.0 ± 5.3 years) completed a 15-day crossover study comparing typical artificial indoor lighting versus a simulated sunset using tunable LEDs (Acuity Brands-Rubik). After 1 week maintaining an ~8h sleep schedule, participants arrived at the laboratory 6h prior to habitual bedtime. Typical electrical indoor home lighting was <90 lux in angle of gaze until scheduled bedtime (<467 lux maximum at 183 cm in the direction of the ceiling mounted light fixtures; 3,500K). To simulate sunset, a simple least square fit was used to match relative spectral irradiance of the laboratory LED lighting to solar spectral irradiance of a standard mid-latitude summer atmosphere in Boulder, Colorado with solar elevation angles ranging from 3.9 degrees to 0 degrees (sunset). The first 3h30min of the simulation was typical indoor lighting of <90 lux (angle of gaze; 3,500K) followed by a 25 min transition in spectral irradiance and then 2h5min at ~7 lux in the angle of gaze (<38 lux maximum at 183 cm; 2,700K).

Results

Melatonin levels were initially similar between conditions but were significantly higher (p<0.05) after the sunset transition in the simulated sunset condition compared to the typical electrical indoor home lighting condition.

Conclusion

These preliminary findings suggest that simulating a sunset transition with tunable LED technology prior to habitual bedtime in the evening has potential to benefit circadian health.

Support

This work was supported in part by NIH R01 HL135598 and NASA Award 80NSSC17K0569.
0035 Resting Metabolism and the Metabolic Response to Exercise Follow Circadian Patterns with Day/Night Differences in Substrate Utilization Between Lean and Obese Adults
Authors: McHill A W , Thosar S S , Bowles N P , Emens J S , Purnell J Q , Gillingham M , Shea S A
Published: May 2020

Introduction

Resting energy expenditure (EE) follows a circadian rhythm in healthy lean participants, with a nadir in the early morning hours. We determined: (1) whether this pattern persists (or how substrate utilization may change), when challenged with exercise, and; (2) whether obesity affects these responses.

Methods

Fourteen participants (aged 48.5±12.8y; 6-female; 5-obese, BMI 31.9±1.4kg/m2 [avg±SD]) underwent a 5-day inpatient forced desynchrony protocol, comprised of ten 5h 20min ‘days’ in dim-lighting and free of time cues. Resting EE was measured immediately prior to a 15-minute cycle ergometer exercise bout at 50% of estimated heart rate maximum. Substrate utilization was determined from the respiratory quotient (RQ). Circadian phase was calculated using the salivary dim-light melatonin onset (>3pg/mL threshold). EE data were analyzed using a mixed-effect model with group (lean vs. obese) and circadian phase as fixed factors; subject was a random factor. RQ was analyzed using t-tests to determine day/night differences in groups at rest and in response to exercise.

Results

Resting and exercising EE both displayed endogenous circadian rhythms (p<0.05) with nadirs in the early morning (~5:30am), without any differences between groups (p>0.22). Resting RQ was similar between the day and night in the lean group (p=0.66), but decreased (suggesting lower carbohydrate utilization) at night within the obese group (-2.5±1.6%, p=0.02). The lean group increased RQ in response to exercise both during the day (+8.9±2.8%) and night (+8.0±2.8%) (both p<0.001), but there was no increase in RQ in the obese group during either day or night exercise (p>0.16).

Conclusion

These data demonstrate that EE during rest and exercise follows a circadian pattern, with limited influence of obesity. Circadian differences in substrate utilization between lean and obese in the resting state and in response to exercise may play a role in expression and maintenance of unwanted weight gain and impaired metabolic health.

Support

R01HL125893, R01HL140577, KL2TR002370, K01HL146992, F32HL131308, Medical Research Foundation of Oregon, Ford Foundation, and CTSA grant (UL1TR000128)
0057 Actigraphy-Based Circadian Measures and Cerebrospinal Fluid Biomarkers of Neurodegeneration in Alzheimer’s Disease with Mild Cognitive Impairment
Authors: Mehra R , Bhambra R , Bena J , Bekris L , Leverenz J , Rao S , Foldvary-Schaefer N , Rao S , Pillai J
Published: May 2020

Introduction

Although recent data implicates sleep and circadian disruption to neurodegeneration in Alzheimer’s Disease (AD), the association of objective circadian biomarkers and neurodegeneration remains understudied. We hypothesize that actigraphy-based circadian measures are associated with cerebrospinal fluid (CSF) biomarkers of neurodegeneration in those mild cognitive impairment due to AD (MCI-AD).

Methods

Eighteen patients with CSF biomarker-confirmed MCI-AD underwent actigraphy monitoring generating the following circadian measures: amplitude, F-ratio and mesor and morning collection of CSF biomarkers of neurodegeneration (Aβ42,t-tau,p-tau). Linear models were used to evaluate the association of circadian and CSF measures; logarithmic transformations were performed on neurodegenerative markers for greater normality. Analysis was performed using SAS software. A significance level of 0.05 was assumed for all tests.

Results

Eighteen MCI-AD patients who were 68± 6.2 years, 44% female, with median AHI=12 and underwent actigraphy monitoring for 8.2+/-3.2 days were included. There was no significant association of circadian measures and Aβ42 nor with mesor and neurodegeneration biomarkers. Amplitude was associated with both p-tau and t-tau, such that each 10 unit increase in amplitude resulted in a predicted increase in p-tau of 8% (95% CI:1%-15%, p=0.018) and an increase of 13% (3%-23%; p=0.01) in t-tau. F-ratio was positively associated with p-tau and t-tau; each 1000 unit increase in F-ratio resulted in a predicted 12% (4%-22%; p=0.007) increase in P-tau and 20%(6%-35%; p=0.005) increase in t-tau. Associations of these circadian measures and CSF levels of p-tau and t-tau remained statistically significant after adjustment for age and sex.

Conclusion

Among patients with symptomatic MCI stages of AD, objective measures of circadian rhythm disruption are associated with CSF-based biomarkers of neurodegeneration even after consideration of age and sex. Future investigation should clarify directionality of this association and potential utility of circadian-based interventions in the mitigation of AD progression.

Support

N/A
0071 A Medullary Circuit Controlling REM Sleep
Authors: Schott A , Baik J , Chung S , Weber F
Published: May 2020

Introduction

Rapid eye movement (REM) sleep is a distinct brain state known for its association with vivid dreaming in humans, though it is also crucial for other mental processes such as memory consolidation and emotion regulation. REM sleep is punctuated by phasic neurophysiological events known as pontine (P)-waves, which are thought to contribute to the cognitive functions of REM sleep. However, little is known about the neural circuits regulating these P-waves, or those responsible for initiating REM sleep itself. Here, we show that a yet unstudied population of medullary neurons expressing corticotropin-releasing-hormone (CRH) are important for controlling both the induction of REM sleep and its phasic events.

Methods

To measure the endogenous activity of CRH+ neurons in the dorsomedial medulla (dmM), we injected the calcium indicator GCaMP6 in the dmM of CRH-Cre mice. To optogenetically manipulate dmM CRH+ neuron activity, we delivered either an excitatory (ChR2) or inhibitory (iC++) opsin to the dmM of CRH-Cre mice. To record P-waves, we implanted microelectrodes to record local field potentials in the subcoeruleus region of the pons.

Results

Fiber photometry recordings showed that dmM CRH+ neurons are selectively active during REM sleep, and optogenetic stimulation and inhibition of this population is sufficient to promote and reduce REM sleep, respectively. Additionally, dmM CRH+ neuron activity is correlated with P-waves in the pons, and optogenetic activation of dmM CRH+ cells reliably triggers P-waves during REM sleep. Finally, histological examination of fluorescently labeled dmM CRH+ axons revealed strong projections to several pontine areas involved in P-wave generation as well as modulation of the theta rhythm during REM sleep.

Conclusion

Our results suggest that dmM CRH+ neurons are involved in controlling REM sleep initiation as well as phasic events within REM sleep. These neurons thus constitute an important component of the brainstem circuitry regulating REM sleep.

Support

National Institutes of Health (R01 HL149133)
0075 Neural Correlates of Cognitive Fatigue in Parkinson Disease
Authors: Liu W , Bhavsar R , Mamikonyan E , Yang F N , Lei H , Weintraub D , Detre J A , Rao H
Published: May 2020

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disease affecting millions of people world-wide. Fatigue is a prevalent and debilitating non-motor symptom in PD. However, the neural correlates underlying cognitive fatigue are poorly understood. Our previous studies suggested that continuous performance of a simple but mentally demanding psychomotor vigilance task (PVT) induced cognitive fatigue, operationalized as subjective exhaustion and time-on-task performance decline. Here we used arterial spin labeling (ASL) perfusion fMRI to investigate regional cerebral blood flow (CBF) changes in PD patients during cognitive fatigue induced by continuous performance of 20-min PVT.

Methods

Twenty-one PD patients completed a 20-min PVT during the ASL scan and two additional 4-min resting-state ASL scans before and after PVT. Reaction times (RTs) and regional CBF changes throughout the PVT as well as during pre- and post-task resting baselines were measured. Cognitive fatigue was analyzed by dividing the entire PVT performance into five quintiles in addition to the immediate measurement of self-rated fatigue before and after PVT.

Results

PD patients demonstrated significantly increased self-reported fatigue ratings after the task (p < 0.05) and progressively slower RTs across quintiles (p < 0.05). Perfusion data showed that the PVT activates the right middle frontal cortex, right inferior parietal lobe, right insula, bilateral occipital cortex, and right cerebellum (FDR corrected). Moreover, the bilateral middle frontal gyri were less active during the post-task rest compared to the pre-task rest.

Conclusion

These results demonstrated that cognitive fatigue has an ongoing effect on brain activity after a period of continuous mental effort and supported the critical role of prefrontal cortex in mediating cognitive fatigue in PD. The findings also suggest the utility of continuous PVT as an appropriate paradigm to induce and examine cognitive fatigue in PD.

Support

Supported in part by Parkinson’s Foundation Translational Research Grant and NIH grants R01-MH107571, R21-AG051981, and P30-NS045839.
1009 Sleep Apnea and Colorectal Adenoma in the Veteran Population: A Case-Control Study
Authors: Guan L , Jiao L , Malhotra S
Published: May 2020

Introduction

Colorectal cancer is the third most common cancer in the United States, with over half of colorectal cancers estimated to be the result of modifiable risk factors. Studies relating sleep apnea (SA) and colorectal adenoma (CRA) are limited and the findings are equivocal. The objective of this study was to examine the association between SA and risk of CRA.

Methods

This was a retrospective cross-sectional case-control study of data collected from 460 veterans, ages 50-79, seen in the colonoscopy clinic at the Michael E. DeBakey VA Medical Center between 2014 and 2018. Information on demographics, sleep history, and co-morbidities were obtained through lifestyle questionnaire. Self-reported SA was diagnosed by a prior sleep study. Cases consisted of 297 participants had pathologically confirmed adenoma (including 117 participants having advanced CRA with villous component or diameter of polyp > 1 cm). Controls consisted of 173 polyp-free participants. The distribution of demographics and lifestyle factors were compared between CRA and non-CRA using the Student’s t or chi-square tests. Odds ratios (OR) and 95% confidence intervals (CI) of CRA in association with CRA were calculated using univariate and multivariate unconditional logistic regression models. The confounding factors included age, sex, ethnicity, obesity, smoking status, alcohol use, hypertension, and sleep duration.

Results

Compared with non-SA, the multivariable OR (95% CI) for CRA was 0.92 (0.58-1.48); for non-advanced CRA was 1.14 (0.68-1.91), and for advanced CRA was 0.61 (0.32-1.17) in SA participants. Adjustment of sleep duration in the model did not change the risk estimates.

Conclusion

Sleep-study diagnosed SA was not associated with development of CRA in this veteran population. Further studies are needed to confirm this observation and incorporate the severity and treatment of SA, and undiagnosed SA in risk assessment.

Support

This research is supported in part by the Gillson Longenbaugh Foundation, and Golfers Against Cancer organization (to LJ), the Cancer Prevention Research Institute of Texas (CPRIT) (RP#140767, to LJ).
1012 Urologic Features Related to the First Uninterrupted Sleep Period (FUSP) in Nocturia
Authors: Monaghan T F , Agudelo C W , Rahman S N , Michelson K P , Lazar J M , Everaert K , Weiss J P , Bliwise D L
Published: May 2020

Introduction

In nocturia, longer FUSP (time to first void) correlates with better quality sleep (Bliwise et al, JCSM 2015;11:53-5) and, with treatment, longer FUSP is associated with decreased nightly voids (Epstein et al, Neurourol Urodyn 2018;37:186-91). We examined urologic correlates of FUSP in an outpatient nocturia population without comorbidities (CHF, OSA, ESRD, diuretics).

Methods

Participants (n=119; men) kept a home flow/volume diary, tracking clock time and quantity of each urination across a 24-hr period. FUSP was defined as time between going to bed and time of first void. We analyzed the urine volume at first nocturnal void (FNVV) (i.e., at end of FUSP). We also analyzed all nighttime volumes and divided by reported hours of sleep to impute nocturnal urine production (NUP) (in ml/hr, classified as high [>90 ml/hr] [n=49] vs low [<90 ml/hr] [n=60])—a measure correlated with number of nocturia episodes (van Doorn et al, J Urol 2014;191:1034-9). Nocturnal maximal voided volume (NMVV) at any single nocturnal void defined maximal functional nocturnal bladder capacity. Data were analyzed non-parametrically.

Results

For 53 of 119 patients, FNVV was identical to NMVV. This was more likely in patients with NUP >90 ml/hr vs <90 ml/hr (59% vs 40%, p=.046). High (vs low) NUP rates were also associated with higher FNVV (300 [225-420] vs 135 [100-200] ml, p<.001), as well as higher number of voids (3 vs. 2, p=.03).

Conclusion

For nearly half of these nocturia patients, the volume at first void occurred at their maximal nocturnal volume. In nocturia, higher FNVV also reflects greater overall nocturnal volume of urine produced, and excess urine volume (as opposed to insufficient bladder capacity) likely plays a central role in the pathogenesis of nocturia in these patients. The extent to which these higher initial volumes represent free-water vs solute-driven clearance is currently under investigation.

Support

N/A
0105 Working Memory Impairment Due to Chronic Sleep Restriction, Dose Response to Recovery and Re-Exposure
Authors: Kaizi-Lutu M , Jones C , Mange A , Basner M , Dinges D F
Published: May 2020

Introduction

Chronic sleep restriction negatively effects working memory. Recovery sleep following sleep restriction partially restores working memory performance. This study examines the impact of chronic sleep restriction and subsequent recovery sleep dose on the N-Back Task (N-Back), a valid measure of working memory.

Methods

N=223 participants (29.9±6.9 years; 48.4% female), completed two baseline nights of 8h time in bed (TIB), followed by five nights of 4h TIB, and were then randomized to a sleep dose of 0, 2, 4, 6, 8, 10, or 12 h TIB. A subset of participants (n=73) were re-exposed to another five nights of 4h TIB. Participants completed the three versions of the N-Back (i.e. 1-Back, 2-Back, and B-back) every two hours during wakefulness and daily averages were computed. Mixed effects and linear regression models were used to assess the impact of sleep restriction and the sleep dose response on percent correct on the N-Back corrected for baseline.

Results

N=219 participants had valid working memory data. The 2-Back (β =-4.5%; P<0.0001) and the 3-Back (β =-12.5%; P<0.0001) were more difficult than the 1-Back. Working memory performance declined across days of sleep restriction for all N-Backs: 1-Back (β =-1.10%; P<0.0001), 2-Back (β =-0.99%; P<0.0001), and 3-Back (β =-1.10%; P<0.0001). The sleep dose analysis revealed a positive association with N-Back performance for all N-Back versions, 1-Back (β =0.99%; P=0.0002), 2-Back (β =1.46%; P<0.0001), and 3-Back (β =1.43%; P<0.0001). Re-exposure to only one night of 4h TIB following recovery sleep resulted in performance decrements equal to performance prior to recovery sleep for all N-Back versions (Ps>0.41).

Conclusion

These data indicate that working memory is adversely impacted by sleep restriction, and that sufficient recovery sleep, possibly across consecutive days, is necessary to maintain optimal working memory performance.

Support

Funded by National Institute of Health NIH R01NR004281 and National Space and Biomedical Research Institute NSRBI NCC 5–98
1034 Should We Recommend More Sleep To Prevent Obesity?
Authors: Kim D S , Foster B E , Collen J F , Eliasson A H
Published: May 2020

Introduction

According to the 2015-2016 National Health and Nutrition Examination Survey (NHANES), the national adult obesity rate was 40% with the incidence of adult obesity having increased by 70% over the last 30 years. Paralleling the obesity epidemic have been worsening sleep deprivation and eroding sleep quality. We analyzed data from a Cardiovascular Health Registry to explore a link between total sleep time and obesity.

Methods

Registry participants underwent anthropometrics and completed validated questionnaires assessing health behaviors and symptoms including total sleep time (TST), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Pittsburgh Sleep Quality Index (PSQI), Perceived Stress Scale (PSS), and exercise time. Differences between subjects with sufficient (≥7 hours) and insufficient (<7 hours) sleep were analyzed using T-tests.

Results

Registry participants (n=630) had mean age 55.3±9.9 years (45% men, 391W, 182B, 26H, 12A, 19O). The subgroup with sufficient sleep (n=261, 48% men), had mean BMI 29.3±5.6 while the subgroup with insufficient sleep (n=369, 44% men) had mean BMI of 30.5±5.3, p=0.008. The insufficient sleep group was noted to be sleepier (ESS 9.7±4.9 vs 7.4±4.6, p<0.001), more fatigued (FSS 4.9±2.3 vs 3.5±2.4, p<0.001) and have worse sleep quality (PSQI 8.6±3.7 vs 4.7±2.8, p<0.001). Insufficient sleepers also perceived greater stress levels (PSS 22.2±8.4 vs 18.9±6.2, p<0.001), and showed a trend toward less exercise per week (143±134 vs 163±106 minutes, p=0.13).

Conclusion

Participants with insufficient sleep were significantly more overweight on average and were more symptomatic for insufficient sleep. While current approaches to weight management focus largely on diet and physical activity, the data from this study suggest that insufficient sleep should also be considered as a risk factor for obesity and should be incorporated into management plans for obesity.

Support
1075 Sleep-stage Independent Electroencephalography Features For Classification Of Veterans With Post-traumatic Stress Disorder
Authors: Laxminarayan S , Wang C , Oyama T , Cashmere D , Germain A , Reifman J
Published: May 2020

Introduction

Prior sleep studies have suggested that electroencephalography (EEG) spectral power and synchrony features in certain sleep stages differ significantly at the group-average level between subjects with and without post-traumatic stress disorder (PTSD). Here, we investigated whether a multivariate combination of sleep-stage independent EEG features could objectively identify individual subjects with PTSD.

Methods

We analyzed EEG data recorded from 78 combat-exposed veteran men with (n = 31) and without (n = 47) PTSD during two consecutive nights of sleep. For each subject we computed 780 features from 10 EEG channels covering the whole brain, by averaging the values over the entire night regardless of sleep stage. Using a training set consisting of the first 47 consecutive subjects (18 with PTSD) of the study, we performed univariate feature selection and backward feature elimination using a logistic regression model. We then evaluated the model on the test set, which consisted of the remaining 31 subjects (13 with PTSD). We assessed model performance by computing the area under the receiver operating characteristic curve (AUC).

Results

Feature elimination using the logistic regression model yielded three uncorrelated features that were consistently discriminative of PTSD across the two consecutive nights. When we trained the logistic model consisting of these three features using data from both nights of the training set, the model yielded test-set AUCs of 0.84 and 0.80 for Night 1 and Night 2, respectively. These values were considerably larger than the test-set AUCs of the three individual features, which ranged from 0.55 to 0.74 across both nights.

Conclusion

We identified robust, stage-independent, whole-night features and combined them in a logistic regression model to discriminate subjects with and without PTSD. The model yielded AUCs above 0.80 on the test data, showing promise as an objective approach to diagnose PTSD at the individual level.

Support

This work was sponsored by U.S. Defense Health Program (grant No. W81XWH-14-2-0145) and managed by the U.S. Army Military Operational Medicine Program Area Directorate, Ft. Detrick, MD. The study was also supported by the Clinical and Translational Science Institute at the University of Pittsburgh (UL1 TR001857).
1084 Depression and Stress Generation: Can Sleep Quality Bridge the Gap?
Authors: Summers C , Ciesla J , Bean C
Published: May 2020

Introduction

The stress generation literature has established a bidirectional relationship between depression and stress. Not only do stressful life events predict depressive episodes, but a depressive history is also linked to increased, future stressors. One relevant mechanism that has received little attention to account for this relationship is sleep. Sleep difficulties are intertwined with depression, both as a predictive and maintenance factor. Beyond depression, sleep disruption is also a factor in a plethora of stressful events, from an increased risk of automotive accidents to higher reports of interpersonal conflict. The present study explored the role of sleep quality to account for depression’s association with stressors.

Methods

Ninety-six college students (Age: M = 19.56, SE = .20) reported on their depressive symptoms before undergoing a two-week, online diary, where they reported on sleep quality and the number of stressors experienced. A generalized structural equation model (GSEM) was used to test the relevance of sleep quality to account for baseline depressive symptoms predicting average differences in stressors over the diary. Within the GSEM, a multilevel model was used to explore the daily, within-person association between sleep quality and the number of stressors reported.

Results

Baseline depression was predictive of poorer sleep quality (b = .01, p < .001) and more stressors across the diary (b = .02, p = .017). Sleep quality mediated the effect of depression on stress generation (b = .002, p = .036), accounting for 13% of the variance. On a daily level, poorer sleep quality the night before predicted more stressors the next day (b = .16, p = .027).

Conclusion

The results suggest that sleep quality is a relevant mechanism in the prediction of future stressors from depression. Sleep difficulties may represent a pivotal area of future research and intervention target in breaking the cycle between depression and stress generation.

Support

Hammen, C. (1991). Generation of stress in the course of unipolar depression. Journal of Abnormal Psychology, 100, 555-561.

Tsuno, N., Besset, A., & Ritchie, K. (2005). Sleep and depression. The Journal of Clinical Psychiatry, 66, 1254-1269.
1090 Self-Reported Sleep Quality is a Robust Predictor of Depression in Women With Irregular Menstrual Cycles
Authors: Meers J M , Bower J L , Alfano C A
Published: May 2020

Introduction

Menstrual cycle regularity is an important marker of women’s health. Abnormalities are associated with serious health complaints, e.g., infertility, cardiovascular, and metabolic disorders. Cycle irregularity is also linked to depression, anxiety and poor quality sleep. In fact, poor sleep and circadian misalignment may precede menstrual irregularity for some. This study describes sleep and affective characteristics of women with menstrual cycle irregularity compared to regularly cycling women and examined the individual contributions of sleep and menstrual regularity to affective symptoms.

Methods

N=314 (Mage=20.95, SD=2.35) women provided reports of menstrual health characteristics (frequency, duration, related symptoms), sleep over the past month (Pittsburgh Sleep Quality Index; PSQI) and on the previous night, as well as mood (Center for Epidemiologic Studies Depression Scale) and anxiety (State Trait Anxiety Inventory) symptoms.

Results

Among the 20.4% (n=64) of women who endorsed “always irregular” periods, mean cycle length (m=31.33 days, sd=8.5) was significantly greater than among women more regular periods (m= 27.93, sd=3.83, t(55.37)=-2.78, p=.007). This subgroup also reported higher PSQI scores (t(181)=-2.56, p=.011), longer SOL (t(282)=-3.00, p=.003), poorer sleep quality overall (t(299)=-2.35, p=.02), and poorer sleep quality on the previous night (t(300)=2.70, p=.007). Irregular cyclers reported significantly more depressive (t(284)=-2.18, p=.03) but not anxiety symptoms. When sleep and menstrual irregularity were entered into a hierarchical linear regression to examine their relative influence on depressive symptoms (F[2,174]=13.15, p<.001, R2=.13), sleep remained the only significant predictor (b= 1.13, p <.001) and menstrual cycle effects were no longer significant.

Conclusion

In line with previous studies, cycle irregularity was associated with poorer sleep quality and depressive symptoms. Sleep quality was found to be a more robust predictor of depression than menstrual cycle irregularity, suggesting that sleep may underlie the affective disturbances in women with more irregular menstrual cycles.

Support

n/a
1098 Altered Actigraphic Behavioral Activity Rhythm In Depression
Authors: Chen I Y , Neikrug A B , Adams J , McMillan L , Yassa M A , Benca R M
Published: May 2020

Introduction

Disturbances in sleep and behavioral activity rhythms (BAR) are frequently observed in individuals with depression. However, it remains unclear how activity variability across the 24-hour period is specifically associated with this disorder. The present study aimed to examine actigraphy-measured sleep and BAR in depression.

Methods

As part of a larger study, fourteen patients with DSM-5 major depressive episode (27.8±7.7 years, 69.2% female) and 13 healthy controls (21.8±1.2 years, 76.5% female) were evaluated with 7-14 days of wrist-actigraphy. Actigraphy-derived sleep parameters included total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE). Minute-by-minute activity counts were aggregated into hour-by-hour bins; hourly mean activity levels were then generated to depict 24-hour activity patterns (i.e., BAR). Factorial (GroupxTime) mixed models were conducted to examine whether BAR differed between patients with MDD and controls. Generalized Additive Models (GAM), by fitting smoothed nonlinear curves to log-transformed aggregated activity, were performed as exploratory analyses to characterize onset (UP slope) and offset (DOWN slope) of BAR.

Results

Compared to healthy controls, patients with MDD exhibited greater actigraphic TST (p=.026); no other between-group differences were detected for the remaining sleep parameters. Significant between-group differences were observed for mean activity during wakefulness (p<.001). Mixed models assessing hour-by-hour daily activity revealed a significant GroupxTime interaction (p=.001) with significant main effects of group (p=.017) and time (p<.001); patients with MDD had lower activity from 6 to 9 pm (ps<.005). Exploratory GAMs results showed an attenuated DOWN slope in patients with MDD (p=.014), indicating a slower decrease in activity during the evening.

Conclusion

Altered BAR, characterized by an overall dampened activity pattern that was most prominent during the evening, was associated with depression. Furthermore, patients with MDD took longer to wind down in the evening. Future studies are needed to explore the potential benefits of adjunctive interventions addressing both BAR along with sleep in mitigating symptoms of depression.

Support

Research supported by National Institutes of Health R01 MH102392.
1111 Do Sleep Disorder Symptom Endorsements Differ Between ADHD Subtypes?
Authors: Seewald M , Muench A , Alio C , Rosenfield B , DiTomasso R , Rostain A , Ramsay J , Klingman K , Perlis M L
Published: May 2020

Introduction

To date, research on differences in sleep complaints between patients with different subtypes of ADHD has been mixed. On balance, the evidence tends towards ADHD-Combined Presentation (ADHD-C) being associated with more severe sleep and sleep-related daytime complaints than ADHD-Primarily Inattentive (ADHD-I). In order to further assess this issue a surveillance study was undertaken in an active ADHD clinic by adding a comprehensive sleep disorders screener (SDS-CL-25) to the clinical intake procedures. These data were used to ascertain whether the two subtypes differ for any of 13 sleep disorders symptoms.

Methods

Subjects (n = 132; 83 male, 49 female, mean age 32.8, age range 18-79), presenting to the clinic for evaluation for ADHD were given the SDS-CL-25. The SDS-CL-25 is a 25-item instrument developed to screen for multiple sleep disorders at one time (problems are endorsed on a Likert-scale; 0 = never and 4 = more than 5x/week). Endorsements greater than 3x/week were counted as positive for the symptom and less than three days per week was considered negative.

Percent per group was compared using Chi Square Analyses. Cumulative morbidity means were also analyzed using t-tests. The subtype, ADHD-I (n=71) and ADHD-C (N=61), was established using EMR records.

Results

No significant differences between patients with ADHD-I and ADHD-C were detected.

Conclusion

The lack of finding in the present analysis may reflect a lack of difference or a failure to detect differences based on the small sample sizes or lack of statistical control for likely confounders (age, sex, illness severity or chronicity, SES status, etc.). Analyses are ongoing.

Support

No support was provided for this abstract.