Browsing by Subject "Sleep"
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Item Open Access A Shared Neural Substrate for Diverse General Anesthetics and Sleep(2019) Jiang-Xie, Li-FengEver since the initial discovery of general anesthetics almost 170 years ago, how general anesthesia (GA) induces loss of consciousness remains a century-long mystery. In addition, whether diverse anesthetic drugs and sleep share a common neural pathway is hotly debated and largely unknown. Previous studies have established that many GA drugs inhibit neural activity through targeting GABA receptors. Here, by using Fos staining, ex vivo brain slice recording, and eventually in vivo multichannel extracellular electrophysiology, we discovered a core ensemble of hypothalamic neurons in and near the supraoptic nucleus, consisting primarily of peptidergic neuroendocrine cells, which are surprisingly and persistently activated by multiple classes of GA drugs. Strikingly, chemogenetic or optogenetic stimulation of these anesthesia-activated neurons (AANs) strongly potentiated slow-wave sleep and prolonged GA, whereas conditional ablation through diphtheria toxin receptor strategy or inhibition of AANs with optogenetics led to reduced slow-wave oscillation in the brain, significant loss of slow-wave and rapid-eye movement sleep, and shortened durations under GA. Together, these findings identify a previously unknown common neural substrate underlying diverse GA drugs and natural sleep, and further illustrate a crucial role of the neuroendocrine system in regulating global brain states.
Item Open Access Characterizing sleep-wake cycles in dogs (Canis lupus familiaris) using daytime activity levels, sex, and temperament: a longitudinal comparison(2024-04-12) Sandberg, EmilyAcross many species, sleep patterns are associated with variables such as age, sex, daytime activity levels, and temperament. Yet, current research lacks an in-depth characterization of dog sleep patterns and how they vary according to these variables during the critical developmental period of young puppyhood. Such studies are crucial in order to establish dogs as a model organism for studies of sleep and for additional applications in the realms of dog welfare and training. In the present study, we characterized how often and for how long young dogs wake, as well as their barking patterns during sleep. We evaluated sleep behaviors for dogs aged 8-18 weeks and determined longitudinal patterns using a sample of Canine Companions service-dogs-in-training (N=21). Video recordings of dogs were analyzed using a novel coding scheme to determine duration and frequency of awake bouts and barking. Mixed-effects logistic regression models reveal that awake-bout length (minutes) and frequency did not vary significantly by weeks of age, daytime activity levels, or temperament. However, we did find significant sex differences in awake bout length (p<0.009). These results suggest distinct daytime and nighttime temperaments, as well as the importance of this developmental period for developing adultlike sleep patterns. Further study is required to examine sleep behaviors in puppies beyond 18-weeks to better understand how adultlike patterns emerge and the stability of the patterns observed in this study.Item Open Access Development and Preliminary Feasibility of iByte4Health: A Mobile Health (mHealth) Pediatric Obesity Prevention Intervention to Engage Parents with Low-Income of Children 2-9 Years.(Nutrients, 2021-11-25) Tripicchio, Gina L; Kay, Melissa; Herring, Sharon; Cos, Travis; Bresnahan, Carolyn; Gartner, Danielle; Sosinsky, Laura Stout; Bass, Sarah BThis research describes the development and preliminary feasibility of iByte4Health, a mobile health (mHealth) obesity prevention intervention designed for parents with a low-income of children 2-9 years of age. Study 1 (n = 36) presents findings from formative work used to develop the program. Study 2 (n = 23) presents a 2-week proof-of-concept feasibility testing of iByte4Health, including participant acceptability, utilization, and engagement. Based on Study 1, iByte4Health was designed as a text-messaging program, targeting barriers and challenges identified by parents of young children for six key obesity prevention behaviors: (1) snacking; (2) physical activity; (3) sleep; (4) sugary drinks; (5) fruit and vegetable intake; and (6) healthy cooking at home. In Study 2, participants demonstrated high program retention (95.7% at follow-up) and acceptability (90.9% reported liking or loving the program). Users were engaged with the program; 87.0% responded to at least one self-monitoring text message; 90.9% found the videos and linked content to be helpful or extremely helpful; 86.4% found text messages helpful or extremely helpful. iByte4Health is a community-informed, evidenced-based program that holds promise for obesity prevention efforts, especially for those families at the increased risk of obesity and related disparities. Future work is warranted to test the efficacy of the program.Item Embargo Exploring Birthing Parent Needs During the Early Postpartum Period with Emphasis on Sleep and Interactions between Healthcare Team Members, Infants and Birthing Parents(2024) Hepler, Bonnie Marie JonesParents who give birth (e.g., mothers, birthing parents, primary caregivers) experience a vast array of needs during the early postpartum period. While unique needs across all individuals are likely innumerable, generally needs focus on taking care of oneself, taking care of one's infant, and dyadic needs such as feeding an infant. One example of a generalized health need is the physiologic need for the birthing parent to receive sufficient sleep. Yet, birthing parents may experience significant deficits in sleep during the early postpartum period, and these unmet sleep needs can significantly impact the parent’s physical and mental well-being during this crucial and transformative period of life. Therefore, this dissertation study explores the concept of postpartum needs and how they emerge and, in particular, investigates maternal experiences of sleep during the first days postpartum. These topics are explored through two studies. First, in a qualitative descriptive study of 22 birthing parents we assessed their perspectives of postpartum needs and how these needs emerge. Then, using videotaped recordings of 15 postpartum families during an in-depth multiple case study, we used behavioral observation methods to code the experiences of 15 postpartum families and their health care team members as videotaped during postpartum hospitalizations. This study provided key insights into the patterns and context of postpartum maternal sleep and awakenings. These findings include describing the interactions that contributed to a median 2.6 hours of sleep for the birthing parents during the last 24 hours of their inpatient stay. In conclusion, we found that parents experience numerous unmet needs during the postpartum period, best understood within the complex socioecologic context in which they arise. These patient-focused findings elevate the importance of aligning health care services in hospital settings and at home with birthing parent needs.
Item Open Access Field-Based Assessments of Behavioral Patterns During Shiftwork in Police Academy Trainees Using Wearable Technology.(Journal of biological rhythms, 2022-06) Erickson, Melissa L; Wang, Will; Counts, Julie; Redman, Leanne M; Parker, Daniel; Huebner, Janet L; Dunn, Jessilyn; Kraus, William ECircadian misalignment, as occurs in shiftwork, is associated with numerous negative health outcomes. Here, we sought to improve data labeling accuracy from wearable technology using a novel data pre-processing algorithm in 27 police trainees during shiftwork. Secondarily, we explored changes in four metabolic salivary biomarkers of circadian rhythm during shiftwork. Using a two-group observational study design, participants completed in-class training during dayshift for 6 weeks followed by either dayshift or nightshift field-training for 6 weeks. Using our novel algorithm, we imputed labels of circadian misaligned sleep episodes that occurred during daytime, which were previously were mislabeled as non-sleep by Garmin, supported by algorithm performance analysis. We next assessed changes to resting heart rate and sleep regularity index during dayshift versus nightshift field-training. We also examined changes in field-based assessments of salivary cortisol, uric acid, testosterone, and melatonin during dayshift versus nightshift. Compared to dayshift, nightshift workers experienced larger changes to resting heart rate, sleep regularity index (indicating reduced sleep regularity), and alterations in sleep/wake activity patterns accompanied by blunted salivary cortisol. Salivary uric acid and testosterone did not change. These findings show wearable technology combined with specialized data pre-processing can be used to monitor changes in behavioral patterns during shiftwork.Item Open Access Investigating Cognitive/Affective/Sleep disturbance symptoms in Patients Receiving High-Dose Interleukin-2 Therapy(2018) Mann, TaraPatients undergoing intensive treatments for life-limiting chronic illnesses such as cancer often experience severe cognitive, affective, and sleep disturbance symptoms. Immunotherapies such as high-dose Interleukin-2 (IL-2) can result in severe alterations in cognition, affect, and sleep. These alterations not only prevent patients from receiving their full course of treatment but also severely impact the quality of life of patients and their care partners. A mixed-method case study approach was used to investigate the trajectory of these symptoms from three key informants (the patient receiving IL-2, the care partner, and the primary nurse) in ten IL-2 cases over up to four treatment hospitalizations. Quantitative measurement scores and qualitative reports of symptom change were compiled to understand the symptom trajectory within and across treatment hospitalizations.
This dissertation includes a systematic literature review in Chapter 2 that highlights the lack of trajectory analysis surrounding cognitive, affective, and sleep disturbance symptoms in patients undergoing IL-2, as well as the gravity and impact that these symptoms have on patients and their families. Chapter 3 features the study team’s evaluation of methods using a case study approach to collect quantitative and qualitative data from one patient, care partner, and primary nurse as a case triad to examine cognitive, affective, and sleep disturbance symptoms one patient diagnosed with MRCC experienced during one hospitalization for IL-2 treatment and served as the foundation for the larger study. Chapters 4 and 5 synthesized data from case informants in the larger study and described the trajectory of cognitive symptoms and affective and sleep disturbance symptoms, respectively, that patients receiving IL-2 therapy for renal cell carcinoma experienced within and across hospitalizations.
Cognitive, affective, and sleep disturbance symptoms are often synergistic and interdependent. Of these symptoms, fatigue and anxiety were the most frequently reported, worsening with each subsequent dose of IL-2, suggesting a cumulative dosing effect. Interventions should be uniquely designed to target patients receiving IL-2, care partners, nurses, and the healthcare team with the aim of reducing commonly reported yet severely incapacitating symptoms. A reduction in these symptoms can reduce other cognitive, affective, and sleep disturbance symptoms, improving the patient’s overall symptom trajectory experience.
Item Open Access Periodic limb movements during sleep and risk of hypertension: A systematic review.(Sleep medicine, 2023-02) Srivali, Narat; Thongprayoon, Charat; Tangpanithandee, Supawit; Krisanapan, Pajaree; Mao, Michael A; Zinchuk, Andrey; Koo, Brain B; Cheungpasitporn, WisitBackground
Several studies suggest an association between periodic limb movements during sleep (PLMS) and hypertension; however, a systematic evaluation of this relationship is lacking.Methods
We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio, comparing the risk of hypertension in persons with PLMS (defined by the level of periodic limb movements per hour of sleep depended on individual studies) versus those without PLMS. After assessing heterogeneity and bias, the pooled risk ratio and 95% confidence intervals (CIs) were determined using a random-effect, generic inverse variance method of DerSimonian and Laird.Results
Out of 572 potentially relevant articles, six eligible studies were included in the data analysis. Studies (6 cross-sectional) included 8949 participants. The statistical heterogeneity of this study was insignificant, with an I2 of 0%. A funnel plot and Egger's regression asymmetry test showed no publication bias with P-value ≥0.05. The pooled risk ratio of hypertension in patients with PLMS was 1.26 (95% CI, 1.12-1.41).Conclusions
Our analysis demonstrates an increased hypertension risk among patients with PLMS. Prospective or interventional studies are needed to confirm this association.Item Unknown Quality improvement initiative to improve infant safe sleep practices in the newborn nursery.(BMJ open quality, 2022-08) Shaikh, Sophie Kay; Chamberlain, Lauren; Nazareth-Pidgeon, Kristina Marie; Boggan, Joel CThe American Academy of Pediatrics recommends that healthcare professionals model their safe infant sleeping environment recommendations, yet adherence to safe sleep practices within our community hospital mother-baby unit was low. We used quality improvement (QI) methodology to increase adherence to infant safe sleep practices, with a goal to improve the proportion of infants sleeping in an environment that would be considered 'perfect sleep' to 70% within a 1-year period. The project occurred while the hospital was preparing for Baby Friendly certification, with increased emphasis on rooming in and skin to skin at the same time.Multiple Plan-Do-Study-Act cycles were performed. Initial cycles targeted nurse and parental education, while later cycles focused on providing sleep sacks/wearable blankets for the infants.While we did not meet our goal, the percentage of infants with 'perfect sleep' increased from a baseline of 41.9% to 67.3%, and we also saw improvement in each of the individual components that contribute to this composite measure. Improvements were sustained over 12 months later, suggesting that QI interventions targeting infant safe sleep in this inpatient setting can have long-lasting results. This project also suggests that infant safe sleep QI initiatives and preparation towards Baby Friendly Hospital Certification can be complementary.Item Unknown Relationship between sleep and exercise as colorectal cancer survivors transition off treatment.(Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2018-08) Coles, Theresa; Bennett, Antonia V; Tan, Xianming; Battaglini, Claudio L; Sanoff, Hanna K; Basch, Ethan; Jensen, Roxanne E; Reeve, Bryce BThe primary objective of this study was to evaluate the relationship between exercise and sleep disturbance in a sample of individuals diagnosed with stage I, II, and III colorectal cancer (CRC) as patients transitioned off first-line treatment. We also sought to identify heterogeneity in the relationship between sleep disturbance and exercise.Data were obtained from the MY-Health study, a community-based observational study of adults diagnosed with cancer. Patient-Reported Outcomes Measurement Information System® (PROMIS) measures (e.g., PROMIS Sleep) were administered, and participants self-reported demographics, comorbidities, cancer treatment, and exercise. Regression mixture and multiple regression models were used to evaluate the relationship between sleep disturbance and exercise cross-sectionally at an average of 10 months after diagnosis, and the change in sleep disturbance over a 7-month period, from approximately 10 to 17 months post-diagnosis.Patients whose exercise was categorized as likely at or above American College of Sports Medicine's guidelines did not report statistically better sleep quality compared to patients who were classified as not active. However, retirement (B = - 2.4), anxiety (B = 0.21), and fatigue (B = 0.24) had statistically significant relationships with sleep disturbance (p < 0.05). Increase in exercise was not significantly associated with a decrease in sleep disturbance. No statistical heterogeneity was revealed in the relationship between sleep and exercise.Further prospective research using an objective measure of exercise is warranted to confirm or refute the nature of the relationship between exercise and sleep disturbance in individuals diagnosed with CRC transitioning off first-line treatment.Item Open Access Sequential psychological and pharmacological therapies for comorbid and primary insomnia: study protocol for a randomized controlled trial.(Trials, 2016-03-03) Morin, Charles M; Edinger, Jack D; Krystal, Andrew D; Buysse, Daniel J; Beaulieu-Bonneau, Simon; Ivers, HansBACKGROUND: Chronic insomnia is a prevalent disorder associated with significant psychosocial, health, and economic impacts. Cognitive behavioral therapies (CBTs) and benzodiazepine receptor agonist (BzRA) medications are the most widely supported therapeutic approaches for insomnia management. However, few investigations have directly compared their relative and combined benefits, and even fewer have tested the benefits of sequential treatment for those who do not respond to initial insomnia therapy. Moreover, insomnia treatment studies have been limited by small, highly screened study samples, fixed-dose, and fixed-agent pharmacotherapy strategies that do not represent usual clinical practices. This study will address these limitations. METHODS/DESIGN: This is a two-site randomized controlled trial, which will enroll 224 adults who meet the criteria for a chronic insomnia disorder with or without comorbid psychiatric disorders. Prospective participants will complete clinical assessments and polysomnography and then will be randomly assigned to first-stage therapy involving either behavioral therapy (BT) or zolpidem. Treatment outcomes will be assessed after 6 weeks, and treatment remitters will be followed for the next 12 months on maintenance therapy. Those not achieving remission will be offered randomization to a second, 6-week treatment, again involving either pharmacotherapy (zolpidem or trazodone) or psychological therapy (BT or cognitive therapy (CT)). All participants will be re-evaluated 12 weeks after the protocol initiation and at 3-, 6-, 9-, and 12-month follow-ups. Insomnia remission, defined categorically as a score < 8 on the Insomnia Severity Index, a patient-reported outcome, will serve as the primary endpoint for treatment comparisons. Secondary outcomes will include sleep parameters derived from daily sleep diaries and from polysomnography, subjective measures of fatigue, mood, quality of life, and functional impairments; and measures of adverse events; dropout rates; and treatment acceptability. Centrally trained therapists will administer therapies according to manualized, albeit flexible, treatment algorithms. DISCUSSION: This clinical trial will provide new information about optimal treatment sequencing and will have direct implication for the development of clinical guidelines for managing chronic insomnia with and without comorbid psychiatric conditions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01651442 , Protocol version 4, 20 April 2011, registered 26 June 2012.Item Open Access Sleep Disorders in Childhood Neurogenetic Disorders(Children, 2017-09-12) Dosier, Laura; Vaughn, Bradley; Fan, ZhengGenetic advances in the past three decades have transformed our understanding and treatment of many human diseases including neurogenetic disorders. Most neurogenetic disorders can be classified as "rare disease," but collectively neurogenetic disorders are not rare and are commonly encountered in general pediatric practice. The authors decided to select eight relatively well-known neurogenetic disorders including Down syndrome, Angelman syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, congenital central hypoventilation syndrome, achondroplasia, mucopolysaccharidoses, and Duchenne muscular dystrophy. Each disorder is presented in the following format: overview, clinical characteristics, developmental aspects, associated sleep disorders, management and research/future directions.Item Open Access Sleep disturbance, dyspnea, and anxiety following total joint arthroplasty: an observational study.(Journal of orthopaedic surgery and research, 2022-08-19) George, Steven Z; Bolognesi, Michael P; Ryan, Sean P; Horn, Maggie EBackground
Patient-Reported Outcomes Measurement Information System (PROMIS) domains for sleep disturbance, anxiety, and dyspnea have been under-reported for total joint arthroplasty (TJA). The aims of this study were to report postoperative differences for these domains based on TJA location and chronic pain state. We also investigated whether these domains were associated with physical function and pain interference outcomes.Methods
This was a retrospective, observational study of patients who underwent hip, knee, or shoulder TJA (primary and revision surgeries) at a single academic tertiary referral center. A subset of these patients completed an email-based survey for chronic pain grade (Chronic Pain Grade Scale-Revised) and sleep disturbance, anxiety, dyspnea, physical function, and pain interference (PROMIS short forms). Pre-operative and operative data were extracted from the electronic health record. Data analysis investigated PROMIS domains for differences in TJA location and chronic pain grade. Hierarchical linear regression determined associations of these domains with physical function and pain interference.Results
A total of 2638 individuals provided informed consent and completed the email survey. In the ANOVA models for sleep disturbance, anxiety, and dyspnea, there was no location by chronic pain grade interaction (p > 0.05) and no difference based on TJA location (p > 0.05). There were differences for chronic pain grade (p < 0.01). The poorest postoperative outcome score for each domain was associated with high impact chronic pain. Furthermore, sleep disturbance and dyspnea had the strongest associations with physical function and pain interference (p < 0.01).Conclusions
Sleep disturbance, anxiety, and dyspnea did not vary based on TJA location, but were associated with postoperative chronic pain grade. Sleep disturbance and dyspnea were strongly associated with commonly reported outcomes of physical function and pain interference. These findings provide guidance for those interested in expanding TJA outcome assessment to include sleep disturbance, anxiety, and/or dyspnea.Item Open Access Sleep Disturbances in Cervical Spondylotic Myelopathy: Prevalence and Postoperative Outcomes-an Analysis From the Quality Outcomes Database.(Clinical spine surgery, 2023-04) Bisson, Erica F; Mummaneni, Praveen V; Michalopoulos, Giorgos D; El Sammak, Sally; Chan, Andrew K; Agarwal, Nitin; Wang, Michael Y; Knightly, John J; Sherrod, Brandon A; Gottfried, Oren N; Than, Khoi D; Shaffrey, Christopher I; Goldberg, Jacob L; Virk, Michael S; Hussain, Ibrahim; Shabani, Saman; Glassman, Steven D; Tumialan, Louis M; Turner, Jay D; Uribe, Juan S; Meyer, Scott A; Lu, Daniel C; Buchholz, Avery L; Upadhyaya, Cheerag; Shaffrey, Mark E; Park, Paul; Foley, Kevin T; Coric, Domagoj; Slotkin, Jonathan R; Potts, Eric A; Stroink, Ann R; Chou, Dean; Fu, Kai-Ming G; Haid, Regis W; Asher, Anthony L; Bydon, MohamadStudy design
Prospective observational study, level of evidence 1 for prognostic investigations.Objectives
To evaluate the prevalence of sleep impairment and predictors of improved sleep quality 24 months postoperatively in cervical spondylotic myelopathy (CSM) using the quality outcomes database.Summary of background data
Sleep disturbances are a common yet understudied symptom in CSM.Materials and methods
The quality outcomes database was queried for patients with CSM, and sleep quality was assessed through the neck disability index sleep component at baseline and 24 months postoperatively. Multivariable logistic regressions were performed to identify risk factors of failure to improve sleep impairment and symptoms causing lingering sleep dysfunction 24 months after surgery.Results
Among 1135 patients with CSM, 904 (79.5%) had some degree of sleep dysfunction at baseline. At 24 months postoperatively, 72.8% of the patients with baseline sleep symptoms experienced improvement, with 42.5% reporting complete resolution. Patients who did not improve were more like to be smokers [adjusted odds ratio (aOR): 1.85], have osteoarthritis (aOR: 1.72), report baseline radicular paresthesia (aOR: 1.51), and have neck pain of ≥4/10 on a numeric rating scale. Patients with improved sleep noted higher satisfaction with surgery (88.8% vs 72.9%, aOR: 1.66) independent of improvement in other functional areas. In a multivariable analysis including pain scores and several myelopathy-related symptoms, lingering sleep dysfunction at 24 months was associated with neck pain (aOR: 1.47) and upper (aOR: 1.45) and lower (aOR: 1.52) extremity paresthesias.Conclusion
The majority of patients presenting with CSM have associated sleep disturbances. Most patients experience sustained improvement after surgery, with almost half reporting complete resolution. Smoking, osteoarthritis, radicular paresthesia, and neck pain ≥4/10 numeric rating scale score are baseline risk factors of failure to improve sleep dysfunction. Improvement in sleep symptoms is a major driver of patient-reported satisfaction. Incomplete resolution of sleep impairment is likely due to neck pain and extremity paresthesia.Item Open Access Spike avalanches exhibit universal dynamics across the sleep-wake cycle.(PLoS One, 2010-11-30) Ribeiro, Tiago L; Copelli, Mauro; Caixeta, Fábio; Belchior, Hindiael; Chialvo, Dante R; Nicolelis, Miguel AL; Ribeiro, SidartaBACKGROUND: Scale-invariant neuronal avalanches have been observed in cell cultures and slices as well as anesthetized and awake brains, suggesting that the brain operates near criticality, i.e. within a narrow margin between avalanche propagation and extinction. In theory, criticality provides many desirable features for the behaving brain, optimizing computational capabilities, information transmission, sensitivity to sensory stimuli and size of memory repertoires. However, a thorough characterization of neuronal avalanches in freely-behaving (FB) animals is still missing, thus raising doubts about their relevance for brain function. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we employed chronically implanted multielectrode arrays (MEA) to record avalanches of action potentials (spikes) from the cerebral cortex and hippocampus of 14 rats, as they spontaneously traversed the wake-sleep cycle, explored novel objects or were subjected to anesthesia (AN). We then modeled spike avalanches to evaluate the impact of sparse MEA sampling on their statistics. We found that the size distribution of spike avalanches are well fit by lognormal distributions in FB animals, and by truncated power laws in the AN group. FB data surrogation markedly decreases the tail of the distribution, i.e. spike shuffling destroys the largest avalanches. The FB data are also characterized by multiple key features compatible with criticality in the temporal domain, such as 1/f spectra and long-term correlations as measured by detrended fluctuation analysis. These signatures are very stable across waking, slow-wave sleep and rapid-eye-movement sleep, but collapse during anesthesia. Likewise, waiting time distributions obey a single scaling function during all natural behavioral states, but not during anesthesia. Results are equivalent for neuronal ensembles recorded from visual and tactile areas of the cerebral cortex, as well as the hippocampus. CONCLUSIONS/SIGNIFICANCE: Altogether, the data provide a comprehensive link between behavior and brain criticality, revealing a unique scale-invariant regime of spike avalanches across all major behaviors.Item Open Access The effects of sleep hypoxia on coagulant factors and hepatic inflammation in emphysematous rats.(PLoS One, 2010-10-06) Feng, Jing; Wang, Qing-shan; Chiang, Ambrose; Chen, Bao-yuanOBJECTIVES: To develop a sleep hypoxia (SH) in emphysema (SHE) rat model and to explore whether SHE results in more severe hepatic inflammation than emphysema alone and whether the inflammation changes levels of coagulant/anticoagulant factors synthesized in the liver. METHODS: Seventy-five rats were put into 5 groups: SH control (SHCtrl), treated with sham smoke exposure (16 weeks) and SH exposure (12.5% O(2), 3 h/d, latter 8 weeks); emphysema control (ECtrl), smoke exposure and sham SH exposure (21% O(2)); short SHE (SHEShort), smoke exposure and short SH exposure (1.5 h/d); mild SHE (SHEMild), smoke exposure and mild SH exposure (15% O(2)); standard SHE (SHEStand), smoke exposure and SH exposure. Therefore, ECtrl, SHEShort, SHEMild and SHEStand group were among emphysematous groups. Arterial blood gas (ABG) data was obtained during preliminary tests. After exposure, hepatic inflammation (interleukin -6 [IL-6] mRNA and protein, tumor necrosis factor α [TNFα] mRNA and protein) and liver coagulant/anticoagulant factors (antithrombin [AT], fibrinogen [FIB] and Factor VIII [F VIII]) were evaluated. SPSS 11.5 software was used for statistical analysis. RESULTS: Characteristics of emphysema were obvious in emphysematous groups and ABGs reached SH criteria on hypoxia exposure. Hepatic inflammation parameters and coagulant factors are the lowest in SHCtrl and the highest in SHEStand while AT is the highest in SHCtrl and the lowest in SHEStand. Inflammatory cytokines of liver correlate well with coagulant factors positively and with AT negatively. CONCLUSIONS: When SH is combined with emphysema, hepatic inflammation and coagulability enhance each other synergistically and produce a more significant liver-derivative inflammatory and prothrombotic status.Item Open Access The relationship of sleep with temperature and metabolic rate in a hibernating primate.(PLoS One, 2013) Krystal, Andrew D; Schopler, Bobby; Kobbe, Susanne; Williams, Cathy; Rakatondrainibe, Hajanirina; Yoder, Anne D; Klopfer, PeterSTUDY OBJECTIVES: It has long been suspected that sleep is important for regulating body temperature and metabolic-rate. Hibernation, a state of acute hypothermia and reduced metabolic-rate, offers a promising system for investigating those relationships. Prior studies in hibernating ground squirrels report that, although sleep occurs during hibernation, it manifests only as non-REM sleep, and only at relatively high temperatures. In our study, we report data on sleep during hibernation in a lemuriform primate, Cheirogaleus medius. As the only primate known to experience prolonged periods of hibernation and as an inhabitant of more temperate climates than ground squirrels, this animal serves as an alternative model for exploring sleep temperature/metabolism relationships that may be uniquely relevant to understanding human physiology. MEASUREMENTS AND RESULTS: We find that during hibernation, non-REM sleep is absent in Cheirogaleus. Rather, periods of REM sleep occur during periods of relatively high ambient temperature, a pattern opposite of that observed in ground squirrels. Like ground squirrels, however, EEG is marked by ultra-low voltage activity at relatively low metabolic-rates. CONCLUSIONS: These findings confirm a sleep-temperature/metabolism link, though they also suggest that the relationship of sleep stage with temperature/metabolism is flexible and may differ across species or mammalian orders. The absence of non-REM sleep suggests that during hibernation in Cheirogaleus, like in the ground squirrel, the otherwise universal non-REM sleep homeostatic response is greatly curtailed or absent. Lastly, ultra-low voltage EEG appears to be a cross-species marker for extremely low metabolic-rate, and, as such, may be an attractive target for research on hibernation induction.Item Open Access The sleep effects of tiagabine on the first night of treatment predict post-traumatic stress disorder response at three weeks.(J Psychopharmacol, 2014-05) Krystal, Andrew D; Zhang, Wei; Davidson, Jonathan RT; Connor, Kathryn MINTRODUCTION: We sought to test the hypothesis that improvements in sleep might mediate treatment-related improvements in daytime symptoms of post-traumatic stress disorder (PTSD). We evaluated whether changes in sleep occurring on the first night of tiagabine (a gamma-amino butyric acid (GABA) reuptake inhibitor) administration predicted subsequent PTSD response. METHODS: This was an open-label three-week polysomnographic (PSG) study of nightly treatment with tiagabine dosing from 2-12 mg including 20 adults with PTSD with ≥30 min of self-reported and PSG wake time after sleep onset (WASO). RESULTS: A treatment night 1 decrease in self-reported and PSG WASO and an increase in slow-wave sleep (SWS) accounted for 94% of the variance in week 3 Short PTSD Rating Interview (SPRINT) score, the primary outcome measure (p<0.001). Increased night 1 SWS also accounted for 91% of the variance in Work/School Impairment and 45% of the variance in Social Life Impairment as measured with the Sheehan Disability Scale (p<0.001). These relationships were much stronger correlates of three-week outcome than three-week sleep effects. CONCLUSIONS: The initial sleep response to tiagabine may mediate or be an indicator of the subsequent PTSD response. The findings highlight the importance of sleep maintenance and SWS in the treatment of PTSD and also suggest a potential relationship between SWS and daytime function.