bluuebunny/crossref_metadata_2025_split huggingface dataset:
0804 Enhanced Drug-Induced Sleep Endoscopy: Distinguishing Central from Obstructive Apneas
Authors: Cheong Crystal , Schwartz Alan , Seay Everett , Mora Jorge , Thaler Erica , Dedhia Raj 
Published: May 2022

Abstract

Introduction
Drug-induced sleep endoscopy (DISE) is a useful tool for assessing upper airway collapse in patients with obstructive sleep apnea (OSA) and frequently influences surgical plans. The standard DISE setup of an endoscopic tower with flexible bronchoscope is adequate for visualizing collapse configurations, but endoscopic findings do not always correlate with actual respiratory physiology. We describe our enhanced clinical DISE setup incorporating nasal flow and respiratory effort measurements, which facilitates differentiation between central and obstructive events. Central sleep apnea was detected in two patients who were originally diagnosed with OSA and underwent DISE during hypoglossal nerve stimulation candidacy workup.
Report of Cases: Case 1 is a 58-year-old male with cardiomyopathy, atrial fibrillation and congestive heart failure who was diagnosed with moderate OSA on a home sleep apnea test. He was PAP intolerant due to claustrophobia. DISE during baseline breathing revealed complete anteroposterior collapse at the palate, tongue base and epiglottis. However, central apneas with Cheyne-Stokes breathing were noticed when positive airway pressure (PAP) was applied. A subsequent polysomnogram revealed severe sleep apnea which was primarily central in nature with Cheyne-Stokes breathing and OSA. He declined retrying PAP and opted for phrenic nerve stimulation.
Case 2 is a 48-year-old male with a history of aortic valve repair, hypothyroidism, atrial
fibrillation provoked by excessive thyroxine, hypertension and moderate OSA diagnosed on several polysomnograms. He had been treated previously with nasal and palatal surgery, oral appliances and PAP. DISE revealed complete anteroposterior collapse of the palate and tongue base, but also central apneas during baseline breathing and at low PAP levels. Polysomnogram performed following his DISE confirmed central sleep apnea which was positional in nature. He chose to undergo positional therapy instead of PAP or phrenic nerve stimulation.

Conclusion
The nasal flow and respiratory effort measurements included in our enhanced DISE setup enable the sleep surgeon to recognize the absence of respiratory effort even in the face of soft tissue collapse observed on videoendoscopy. These cases demonstrate the ability of propofol to preserve pathophysiologic mechanisms of sleep apnea (i.e. central versus obstructive), and underscore the importance of DISE as a diagnostic tool prior to sleep surgery.

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NIH 1R01HL144859-01
0818 Psychosis associated with sodium oxybate
Authors: Bhattacharyya Sarathi , Eng Kevin , Harris Brian , Zeidler Michelle 
Published: May 2022

Abstract

Introduction
Sodium oxybate is commonly used to treat narcolepsy with cataplexy. At the approved doses, the most common side effects are typically described as nausea, vomiting, dizziness, hypersomnia, urinary disturbances, and weight loss. Cases of medication-induced psychosis have been reported in the literature but remain exceedingly rare. We present a case of rapid-onset psychosis in a patient with systemic lupus erythematosus, which added complexity to the evaluation, treatment and clinical course.
Report of Cases: The patient is a 42 year old woman with a past history of fibromyalgia, lupus and a prior diagnosis of narcolepsy evaluated for daytime hypersomnia and poor night time sleep. Prior medications included sodium oxybate which was effective; and modafinil and amphetamines which created intolerable side effects. Prior sleep studies were not available and a repeat PSG/MSLT were performed. PSG did not show sleep disordered breathing or nocturnal movements and MSLT showed an average sleep latency of 5.4 minutes and 4 SOREMs. HLA DQB10602 was positive. The patient was reinitiated on sodium oxybate and titrated to 4.5g twice nightly. A few weeks later the patient developed visual hallucinations, persecutory delusions, and insomnia for 3 days. She was admitted for an evaluation to rule out lupus cerebritis, and auto-immune vs. infectious encephalitis. MRI/MRA, lumbar puncture, as well as inflammatory markers and rheumatologic and infectious work up were unrevealing. Sodium oxybate was discontinued on the day of admission and the patient’s mentation returned to baseline over the next few days. Discharge diagnosis was psychosis secondary to sodium oxybate.

Conclusion
Psychosis is an extremely rare side effect of sodium oxybate therapy among patients treated for cataplectic narcolepsy. It remains a diagnosis of exclusion, and any alternative diagnoses must be explored prior to making the diagnosis of psychosis secondary to sodium oxybate, particularly in the medically complex patient.

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0849 Baclofen-induced severe central sleep apnea
Authors: Agrawal Ritwick , Teague Taylor 
Published: May 2022

Abstract

Introduction
Baclofen is a gamma-aminobutyric acid-B agonist that targets neurons in the spinal cord and brain. It has skeletal muscle-relaxant properties and is FDA approved to treat spasticity from spinal cord injury (SCI), multiple sclerosis, or traumatic brain injury. Off label use includes treatment of alcohol use disorder, hiccups, and muscle spasms. A rare respiratory side effect of baclofen is apnea, with reports of baclofen-induced central sleep apnea (CSA) in a pediatric patient and four adults with alcohol use disorder. We describe a case of severe CSA in a veteran with T7 paraplegia due to chronic baclofen use.
Report of Cases: A 42-year-old veteran with T7 paraplegia was referred to sleep medicine for unrefreshing sleep. He had a remote history of spinal cord injury complicated by spasticity that was being treated with oral baclofen (40 mg TID). Further evaluation of unrefreshing sleep was obtained with baseline polysomnography. A total of 146 apnea and hypopnea events were observed (5 obstructive apneas, 131 central apneas, 4 mixed apneas and 6 hypopneas) for an AHI of 43.2 events/hour. Minimum oxygen saturation was 85% with 0.3 minutes spent &lt;89%. Respiratory pattern was suggestive of crescendo decrescendo breathing but did not meet diagnostic criteria for Cheyne-Stokes respiration (cycle length &lt;40 seconds). Other causes of CSA were investigated but unrevealing. A diagnosis of baclofen-induced central sleep apnea was made.

Conclusion
Spasticity is a common consequence of SCI and is commonly managed with baclofen. Apnea is a rare respiratory side effect of baclofen but can significantly impact patients’ sleep quality and overall quality of life. Our case highlights how providers should have a high suspicion for sleep-disordered breathing in patients with chronic baclofen use.

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1. Ghanavatian S, Derian A. Baclofen. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 15, 2021.2. Locatelli F, Formica F, Galbiati S, et al. Polysomnographic Analysis of a Pediatric Case of Baclofen-Induced Central Sleep Apnea. J Clin Sleep Med. 2019;15(2):351-354. Published 2019 Feb 15. doi:10.5664/jcsm.76443. Olivier PY, Joyeux-Faure M, Gentina T, et al. Severe Central Sleep Apnea Associated With Chronic Baclofen Therapy: A Case Series. Chest. 2016;149(5):e127-e131. doi:10.1016/j.chest.2015.10.001
0852 Narcolepsy Type 1 in a Pediatric Patient with Temporal Lobe Epilepsy
Authors: Najimi Neda , Shahid Asim , Prero Moshe 
Published: May 2022

Abstract

Introduction
Narcolepsy type-1 is clinically characterized by irrepressible daytime sleepiness and REM-sleep dissociation, including cataplexy. Cataplexy usually manifests as episodes of brief, symmetrical sudden loss of muscle tone with retained consciousness. It may be difficult to distinguish from seizure activity as they may share overlapping features. We discuss a pediatric patient with temporal lobe epilepsy with co-occuring Narcolepsy Type 1.
Report of Cases: A 17-year-old boy with obesity and a history of focal epilepsy secondary to intracranial hemorrhage in the neonatal period status-post right parieto-occipital resection at age 11, presented with worsening fall episodes and feeling of imbalance Following surgery, his seizures improved, but he was having excessive sleepiness. At age 13, he started experiencing episodes of slurred speech, feeling of imbalance, “body heaviness and tongue heaviness” with occasional falls. He denied loss of consciousness, body shaking, stiffening, or incontinence.
At age 17, he presented to medical attention due to increasing frequency of such episodes.
Physical exam was significant for BMI 42.7 kg/m , Mallampati 4, tonsils 3+ bilaterally, and homonymous hemianopia. Epworth Sleepiness Scale: 22/24. Video EEG was negative for epileptiform discharges despite occurrence of above-mentioned episodes increasing the clinical suspicion of Narcolepsy. Polysomnography revealed sleep latency of 0 minutes, REM latency of 2.6 minutes, and mild OSA. Toxicology screen was negative. MSLT showed mean sleep latency of 1.2 minutes with 3 SOREMPs. CSF orexin could not be obtained due to technical constraints.
He was diagnosed with Narcolepsy type-1 and started on Venlafaxine and Methylphenidate with resultant improvement in both daytime sleepiness, and the severity and frequency of cataplexy.
However, his feeling of imbalance persisted, prompting repeat video EEG which demonstrated left temporal lobe seizure activity. Anti-epileptic regimen was optimized with improvement in sensation of imbalance.

Conclusion
Temporal lobe epilepsy and Narcolepsy Type-1 can have overlapping features that make it difficult to distinguish between the two. While exceedingly rare, the two entities may co-occur. Diagnostic and therapeutic management require coordination between Sleep Medicine and Neurology. While PSG, MSLT, and CSF Orexin can clarify the diagnosis of narcolepsy, neurologic work up should be pursued if symptoms are not completely attributable to Narcolepsy.

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0858 Under reporting of Apnea Hypopnea Index (AHI) in patients with predominant REM sleep disordered breathing on antidepressants
Authors: Reddy Pratap , Kahn Daron 
Published: May 2022

Abstract

Introduction
The prevalence of Rapid Eye Movement (REM) related Sleep Disordered Breathing (SDB) ranges from 13.5% to 36.7% in patients suspicious to have SDB.1 It is reported that patients with REM related SDB often have associated depression and are commonly on anti-depressants.2 Antidepressants suppress overall REM sleep duration. Significant sleep disordered breathing is known to occur during REM sleep. These patients commonly present with excessive daytime sleepiness and fatigue. Obstructive sleep apnea (OSA) diagnosis is often missed in these patients secondary to REM sleep suppression and subsequent underreporting of AHI.1. Conwell W, Patel B etal 2012 PMID: 21614575. 2. Geckil AA, Ermis H. 2020 PMID: 30949927.
Report of Cases: Case 1 is a 53-year-old obese white female with stable depression on citalopram 20mg presented with witnessed loud snoring and apneas, sleep onset and maintenance insomnia, daytime fatigue and hypersomnolence. Her Epworth Sleep Score (ESS) was 13/24. Her in lab baseline polysomnogram demonstrated overall AHI 3.8/hour and REM only AHI 24.3/hour. To further explore her persistent daytime sleepiness a Mean Sleep Latency Test (MSLT) was ordered. Citalopram was held 2 weeks prior to MSLT. In the PSG her overall AHI increased to 7.6/hour diagnosing her with mild OSA. PAP therapy was initiated that improved patients nocturnal sleep, daytime fatigue and hypersomnolence. Case 2 is a 54-year-old overweight white female with past medical history of chronic stable depression on Wellbutrin SR 100 mg daily presented with significant day time fatigue and hypersomnolence (ESS 15/24). Her baseline PSG reported AHI 1.7/hour with REM only AHI 10.7/hour. However due to persistent excessive daytime sleepiness MSLT was ordered. Her Wellbutrin was held 2 weeks prior to testing. Her overnight PSG demonstrated increase in her AHI to 7.9/hour and REM AHI to 34.2/hour. Mild obstructive sleep apnea was diagnosed, and PAP therapy was initiated that improved her hypersomnolence.

Conclusion
These cases illustrate that antidepressants likely mask obstructive sleep apnea by suppressing REM sleep. Given the underreported AHI in patients with REM SDB who are on anti-depressants it may be prudent to hold anti-depressants for 2 weeks to establish an accurate diagnosis of sleep apnea.

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0862 A unique case of severe sleep onset and maintenance insomnia following COVID-19 vaccination
Authors: Aryal Shubekchha , Kramer Joshua , Azzouz Mouhannad , Stansbury Robert 
Published: May 2022

Abstract

Introduction
The COVID-19 vaccines have documented transient side effects, including injection site soreness, redness, headache, fatigue, and fever. In addition, there have been few reported long-term side effects, including Guillain-Barre, pericarditis, and cerebral venous sinus thrombosis. We present a rare case of severe insomnia as a long-term side effect following COVID-19 vaccination.
Report of Cases: A 59-year-old female with a past medical history of well-controlled hypothyroidism and migraine presented to the sleep center with four months of insomnia. She had a history of COVID infection in November 2020 with only mild symptoms of sore throat and fatigue. The patient finished her two-shot series of the Moderna COVID-19 vaccine in April 2021. Immediately following the vaccination, the patient had severe trouble falling and staying
asleep. Her insomnia was resistant to multiple medications including zolpidem Immediate-release(IR), Controlled-release(CR) formulas, zaleplon, eszopiclone, trazodone, melatonin, clonazepam, suvorexant, and lemborexant. However, magnetic resonance imaging (MRI) brain imaging only showed nonspecific white matter disease. She had no mood disorders or psychosocial stressors, and the patient had excellent sleep hygiene measures. However,
insomnia caused severe impairment of her daily life activities to a point where she was almost
seeking inpatient admission for her insomnia. During the COVID-19 pandemic, the effects on sleep have been significant, particularly insomnia. Prescriptions for sleep medications have increased. Many have attributed the rise of insomnia to pandemic-related stress, disturbance of circadian rhythm from home confinement, and worsening mental health.

Conclusion
To our knowledge, there have not been documented side effects of insomnia on the COVID-19 vaccines, with some studies suggesting sleep deprivation reducing their effectiveness. As vaccination efforts continue worldwide, awareness of side effects from vaccines is paramount for clinicians facing the challenges in patient care.This case demonstrates that chronic insomnia can be a side effect of the COVID-19 vaccines. Therefore, further surveillance of patients and side effects from COVID-19 vaccination is warranted as insomnia can have significant clinical and psychosocial consequences.

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Sox9 and Lef1 Regulate the Fate and Behavior of Airway Glandular Progenitors in Response to Injury
Authors: Ievlev Vitaly , Jensen-Cody Chandler C , Lynch Thomas J , Pai Albert C , Park Soo , Shahin Weam , Wang Kai , Parekh Kalpaj R , Engelhardt John F 
Published: May 2022

AbstractCartilaginous airways of larger mammals and the mouse trachea contain at least 3 well-established stem cell compartments, including basal cells of the surface airway epithelium (SAE) and ductal and myoepithelial cells of the submucosal glands (SMG). Here we demonstrate that glandular Sox9-expressing progenitors capable of SAE repair decline with age in mice. Notably, Sox9-lineage glandular progenitors produced basal and ciliated cells in the SAE, but failed to produce secretory cells. Lef1 was required for glandular Sox9 lineage contribution to SAE repair, and its deletion significantly reduced proliferation following injury. By contrast, in vivo deletion of Sox9 enhanced proliferation of progenitors in both the SAE and SMG shortly following injury, but these progenitors failed to proliferate in vitro in the absence of Sox9, similar to that previously shown for Lef1 deletion. In cystic fibrosis ferret airways, Sox9 expression inversely correlated with Ki67 proliferative marker expression in SMG and the SAE. Using in vitro and ex vivo models, we demonstrate that Sox9 is extinguished as glandular progenitors exit ducts and proliferate on the airway surface and that Sox9 is required for migration and proper differentiation of SMG, but not surface airway, progenitors. We propose a model whereby Wnt/Lef1 and Sox9 signals differentially regulate the proliferative and migratory behavior of glandular progenitors, respectively.
Exploring the Influence of Experimental Design on Toxicity Outcomes in Zebrafish Embryo Tests
Authors: Hsieh Jui-Hua , Behl Mamta , Parham Frederick , Ryan Kristen 
Published: May 2022

Abstract
Compound toxicity data obtained from independent zebrafish laboratories can vary vastly, complicating the use of zebrafish screening for regulatory decisions. Differences in the assay protocol parameters are the primary source of variability. We investigated this issue by utilizing data from the NTP DNT-DIVER database (https://doi.org/10.22427/NTP-DATA-002-00062-0001-0000-1, last accessed June 2, 2022), which consists of data from zebrafish developmental toxicity (devtox) and locomotor response (designated as “neurotox”) screens from 3 independent laboratories, using the same set of 87 compounds. The data were analyzed using the benchmark concentration (BMC) modeling approach, which estimates the concentration of interest based on a predetermined response threshold. We compared the BMC results from 3 laboratories (A, B, C) in 3 toxicity outcome categories: mortality, cumulative devtox, and neurotox, in terms of activity calls and potency values. We found that for devtox screening, laboratories with similar/same protocol parameters (B vs C) had an active call concordance as high as 86% with negligible potency difference. For neurotox screening, active call concordances between paired laboratories are lower than devtox screening (highest 68%). When protocols with different protocol parameters were compared, the concordance dropped, and the potency shift was on average about 3.8-fold for the cumulative devtox outcome and 5.8-fold for the neurotox outcome. The potential contributing protocol parameters for potency shift are listed or ranked. This study provides a quantitative assessment of the source of variability in zebrafish screening protocols and sets the groundwork for the ongoing Systematic Evaluation of the Application of Zebrafish in Toxicology effort at the National Toxicology Program.
Characterization and computational simulation of human Syx, a RhoGEF implicated in glioblastoma
Authors: Boyd Ryan J. , Olson Tien L. , Zook James D. , Stein Derek , Aceves Manuel , Lin Wan‐Hsin , Craciunescu Felicia M. , Hansen Debra T. , Anastasiadis Panos Z. , Singharoy Abhishek , Fromme Petra 
Published: May 2022

AbstractStructural discovery of guanine nucleotide exchange factor (GEF) protein complexes is likely to become increasingly relevant with the development of new therapeutics targeting small GTPases and development of new classes of small molecules that inhibit protein‐protein interactions. Syx (also known as PLEKHG5 in humans) is a RhoA GEF implicated in the pathology of glioblastoma (GBM). Here we investigated protein expression and purification of ten different human Syx constructs and performed biophysical characterizations and computational studies that provide insights into why expression of this protein was previously intractable. We show that human Syx can be expressed and isolated and Syx is folded as observed by circular dichroism (CD) spectroscopy and actively binds to RhoA as determined by co‐elution during size exclusion chromatography (SEC). This characterization may provide critical insights into the expression and purification of other recalcitrant members of the large class of oncogenic—Diffuse B‐cell lymphoma (Dbl) homology GEF proteins. In addition, we performed detailed homology modeling and molecular dynamics simulations on the surface of a physiologically realistic membrane. These simulations reveal novel insights into GEF activity and allosteric modulation by the plekstrin homology (PH) domain. These newly revealed interactions between the GEF PH domain and the membrane embedded region of RhoA support previously unexplained experimental findings regarding the allosteric effects of the PH domain from numerous activity studies of Dbl homology GEF proteins. This work establishes new hypotheses for structural interactivity and allosteric signal modulation in Dbl homology RhoGEFs.
A Comparison of Haitian and American Bachelor of Science in Nursing Students' Perceptions of Cigarette Smoking and E-Cigarette Use
Authors: Ruffin Larider , Padden-Denmead Mary , Lewis Jack B. , Ekwegh Tavonia , Denning Shawn , Calimer Trevor , Crowell Tara 
Published: May 2022

Abstract
Cigarette smoking is a global health epidemic, and smoking along with electronic nicotine delivery systems use or vaping are on the rise. Despite the effectiveness of smoking cessation strategies, healthcare providers and nursing students do not routinely recommend these strategies for patients who are smokers. This study compares the perceptions of smoking and vaping between two groups of baccalaureate degree nursing students from Haiti and the United States. The study was influenced by contemporary and past studies showing that more young people are drawn into smoking and vaping despite the prevalence of antismoking policies and awareness campaigns. In this descriptive study, surveys were used to collect data to determine the differences between the two country's nursing students on their perception of smoking and vaping. The findings indicated that, despite greater usage, the students from the United States had a higher perception of the health implications of cigarette smoking and vaping compared with those from Haiti. On the basis of the findings of this study, collaborative pedagogical research opportunities among international nursing education programs can further curriculum development to foster growth and development of future global health practitioners.
Pediatric Physical Therapists' Perceptions of Telehealth Continuation Post-pandemic: A Thematic Analysis of Open-Ended Survey Responses
Authors: Hall Jamie B. , Luechtefeld Jessica T. , Woods Morgan L. 
Published: May 2022

Purpose:
To explore pediatric physical therapists' (PTs) perceptions about continuing telehealth services post-pandemic.

Methods:
Two open-ended questions from a larger survey were analyzed using a pragmatic application of thematic analysis.

Results:
Two hundred two pediatric PTs in the United States responded. Themes included Telehealth During COVID-19, Benefits, Drawbacks, and Recommendations. Telehealth During COVID-19 acknowledged adopting and providing telehealth during a global pandemic was likely different than at other times. Benefits described perceived positive aspects of telehealth for children, families, and PTs, which support continuation of telehealth post-pandemic. Drawbacks described perceived negative aspects of telehealth for children, families, and PTs, which may dissuade continuation. Recommendations described respondents' recommendations for the continuation of telehealth. Ultimately respondents recommended a hybrid model of telehealth and in-person services going forward.

Conclusions:
A hybrid model of telehealth and in-person services may have the benefits of increasing access, flexibility, efficiency, communication, and home programming across pediatric practice settings.