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Study Objectives Obstructive sleep apnea (OSA) is characterized by multiple “endotypic traits,” including pharyngeal collapsibility, muscle compensation, loop gain, and arousal threshold. Here, we examined (1) within-night repeatability, (2) long-term consistency, and (3) influences of body position and sleep state, of endotypic traits estimated from in-home polysomnography in mild-to-severe OSA (apnea-hypopnea index, AHI > 5 events/h). Methods Within-night repeatability was assessed using Multi-Ethnic Study of Atherosclerosis (MESA): Traits derived separately from “odd” and “even” 30-min periods were correlated and regression (error vs. N windows available) provided a recommended amount of data for acceptable repeatability (Rthreshold = 0.7). Long-term consistency was assessed using the Osteoporotic Fractures in Men Study (MrOS) at two time points 6.5 ± 0.7 years apart, before and after accounting for across-year body position and sleep state differences. Within-night dependence of traits on position and state (MESA plus MrOS data) was estimated using bootstrapping. Results Within-night repeatability for traits ranged from R = 0.62–0.79 and improved to R = 0.69–0.83 when recommended amounts of data were available (20–35 7-min windows, available in 94%–98% of participants); repeatability was similar for collapsibility, loop gain, and arousal threshold (R = 0.79–0.83), but lower for compensation (R = 0.69). Long-term consistency was modest (R = 0.30–0.61) and improved (R = 0.36–0.63) after accounting for position and state differences. Position/state analysis revealed reduced loop gain in REM and reduced collapsibility in N3. Conclusions Endotypic traits can be obtained with acceptable repeatability. Long-term consistency was modest but improved after accounting for position and state changes. These data support the use of endotypic assessments in large-scale epidemiological studies. Clinical Trial Information The data used in the manuscript are from observational cohort studies and are not a part of the clinical trial.

Study Objectives Obstructive sleep apnea has major health consequences but is challenging to treat. For many therapies, efficacy is determined by the severity of underlying pharyngeal collapsibility, yet there is no accepted clinical means to measure it. Here, we provide insight into which polysomnographic surrogate measures of collapsibility are valid, applicable across the population, and predictive of therapeutic outcomes. Methods Seven promising polysomnography-derived surrogate collapsibility candidates were evaluated: Vpassive (flow at eupneic ventilatory drive), Vmin (ventilation at nadir drive), event depth (depth of the average respiratory event), oxygen desaturation slope and mean oxygen desaturation (events-related averages), Fhypopneas (fraction of events scored as hypopneas), and apnea index. Evaluation included (1) validation by comparison to physiological gold-standard collapsibility values (critical closing pressure, Pcrit), (2) capacity to detect increased collapsibility with older age, male sex, and obesity in a large community-based cohort (Multi-Ethnic Study of Atherosclerosis, MESA), and (3) prediction of treatment efficacy (oral appliances and pharmacological pharyngeal muscle stimulation using atomoxetine-plus-oxybutynin). Results Pcrit was significantly correlated with Vmin (r = −0.54), event depth (r = 0.49), Vpassive (r = −0.38), Fhypopneas (r = −0.46), and apnea index (r = −0.46; all p Conclusions Among several candidates, event depth, Fhypopneas, and apnea index were identified as preferred pharyngeal collapsibility surrogates for use in the clinical arena.

The deregulation of microRNAs (miRs) has been identified in tumor development. Indeed, the restoration of tumor-suppressive miRs has been associated with inhibited tumor development in various cancers. Herein, we aimed to evaluate the impact of combined miR-383-5p restoration, as a tumor-suppressive miR, with taxol therapy in suppressing MDA-MB-231 breast cancer development. MDA-MB-231 cell line was restored with miR-383-5p and treated with paclitaxel both in combined and separate manners. The MTT experiment was carried out to measure the cytotoxicity of the therapeutic approaches on the tumoral cells. Besides, flow cytometry was conducted to assess apoptosis and cell cycle status following the treatments. Furthermore, the expression levels of critical factors contributed to tumor proliferation, migration, apoptosis were investigated via the qRT-PCR and western blotting techniques. The outcomes pointed out that the miR-383-5p might substantially enhance the chemosensitivity of MDA-MB-231 to taxol. Besides, miR-383-5p restoration and the combined therapy of miR-383-5p restoration with paclitaxel could remarkably increase apoptosis, decrease cell viability, arrest the cell cycle, inhibit clonogenicity, suppress tumor migration, suppress the PI3K/Akt signaling pathway, and down-regulate PD-L1 expression of BC cells. The restoration of miR-383-5p can enhance the chemosensitivity of MDA-MB-231 cells to taxol. Despite the anti-tumoral effects of miR-383-5p restoration on MDA-MB-231 breast cancer development, the combined therapy of miR-383-5p restoration with paclitaxel can be more effective in repressing MDA-MB-231 breast cancer development.

The deregulation of microRNAs (miRs) has been identified in tumor development. Indeed, the restoration of tumor-suppressive miRs has been associated with inhibited tumor development in various cancers. Herein, we aimed to evaluate the impact of combined miR-383-5p restoration, as a tumor-suppressive miR, with taxol therapy in suppressing MDA-MB-231 breast cancer development. MDA-MB-231 cell line was restored with miR-383-5p and treated with paclitaxel both in combined and separate manners. The MTT experiment was carried out to measure the cytotoxicity of the therapeutic approaches on the tumoral cells. Besides, flow cytometry was conducted to assess apoptosis and cell cycle status following the treatments. Furthermore, the expression levels of critical factors contributed to tumor proliferation, migration, apoptosis were investigated via the qRT-PCR and western blotting techniques. The outcomes pointed out that the miR-383-5p might substantially enhance the chemosensitivity of MDA-MB-231 to taxol. Besides, miR-383-5p restoration and the combined therapy of miR-383-5p restoration with paclitaxel could remarkably increase apoptosis, decrease cell viability, arrest the cell cycle, inhibit clonogenicity, suppress tumor migration, suppress the PI3K/Akt signaling pathway, and down-regulate PD-L1 expression of BC cells. The restoration of miR-383-5p can enhance the chemosensitivity of MDA-MB-231 cells to taxol. Despite the anti-tumoral effects of miR-383-5p restoration on MDA-MB-231 breast cancer development, the combined therapy of miR-383-5p restoration with paclitaxel can be more effective in repressing MDA-MB-231 breast cancer development.

Study Objectives The presence of flow limitation during sleep is associated with adverse health consequences independent of obstructive sleep apnea (OSA) severity (apnea-hypopnea index, AHI), but remains extremely challenging to quantify. Here we present a unique library and an accompanying automated method that we apply to investigate flow limitation during sleep. Methods A library of 117,871 breaths (N = 40 participants) were visually classified (certain flow limitation, possible flow limitation, normal) using airflow shape and physiological signals (ventilatory drive per intra-esophageal diaphragm EMG). An ordinal regression model was developed to quantify flow limitation certainty using flow-shape features (e.g. flattening, scooping); breath-by-breath agreement (Cohen’s ƙ); and overnight flow limitation frequency (R2, %breaths in certain or possible categories during sleep) were compared against visual scoring. Subsequent application examined flow limitation frequency during arousals and stable breathing, and associations with ventilatory drive. Results The model (23 features) assessed flow limitation with good agreement (breath-by-breath ƙ = 0.572, p < 0.001) and minimal error (overnight flow limitation frequency R2 = 0.86, error = 7.2%). Flow limitation frequency was largely independent of AHI (R2 = 0.16) and varied widely within individuals with OSA (74[32–95]%breaths, mean[range], AHI > 15/h, N = 22). Flow limitation was unexpectedly frequent but variable during arousals (40[5–85]%breaths) and stable breathing (58[12–91]%breaths), and was associated with elevated ventilatory drive (R2 = 0.26–0.29; R2 < 0.01 AHI v. drive). Conclusions Our method enables quantification of flow limitation frequency, a key aspect of obstructive sleep-disordered breathing that is independent of the AHI and often unavailable. Flow limitation frequency varies widely between individuals, is prevalent during arousals and stable breathing, and reveals elevated ventilatory drive. Clinical trial registration: The current observational physiology study does not qualify as a clinical trial.

BackgroundIn the classic model of obstructive sleep apnoea (OSA), respiratory events occur with sleep-related dilator muscle hypotonia, precipitating increased neural ventilatory ‘drive’. By contrast, a drive-dependent model has been proposed, whereby falling drive promotes dilator muscle hypotonia to precipitate respiratory events. Here we determine the extent to which the classic versus drive-dependent models of OSA are best supported by direct physiological measurements.MethodsIn 50 OSA patients (5–91 events/hour), we recorded ventilation (‘flow’, oronasal mask and pneumotach) and ventilatory drive (calibrated intraoesophageal diaphragm electromyography, EMG) overnight. Flow and drive during events were ensemble averaged; patients were classified as drive dependent if flow fell/rose simultaneously with drive. Overnight effects of lower drive on flow, genioglossus muscle activity (EMGgg) and event risk were quantified (mixed models).ResultsOn average, ventilatory drive fell (rather than rose) during events (−20 (−42 to 3)%baseline, median (IQR)) and was strongly correlated with flow (R=0.78 (0.24 to 0.94)). Most patients (30/50, 60%) were classified as exhibiting drive-dependent event pathophysiology. Lower drive during sleep was associated with lower flow (−17 (−20 to –14)%/drive) and EMGgg (−3.5 (−3.8 to –3.3)%max/drive) and greater event risk (OR: 2.2 (1.8 to 2.5) per drive reduction of 100%eupnoea); associations were concentrated in patients with drive-dependent OSA (ie, flow: −37 (−40 to –34)%/drive, OR: 6.8 (5.3 to 8.7)). Oesophageal pressure—without tidal volume correction—falsely suggested rising drive during events (classic model).ConclusionsIn contrast to the prevailing view, patients with OSA predominantly exhibit drive-dependent event pathophysiology, whereby flow is lowest at nadir drive, and lower drive raises event risk. Preventing ventilatory drive decline is therefore considered a target for OSA intervention.

Finding the right distance metric is one of the main challenges in machine learning and computer vision procedures. On the other hand, adapting a good classifier with the learned metric has the same importance. In traditional machine learning problems both training and test data come from a same distribution, however it is not common for many real-world data sets. Therefore, they suffer from poor performance where there is inconsistency and dissimilarity between the training (source) data and the test (target) data domain distributions. In this paper, we present a method to overcome this issue efficiently. To this end, a projection matrix is found by learning a cross-domain metric to map the samples of the source and target datasets to a new feature space where the distance of two domains is reduced by utilizing marginal and conditional adaptation terms. Moreover, the metric becomes powerful by employing marginalized de-noising and low-rank strategies. Also, parallel to learning the projection matrix, an adaptive decision function is learned by minimizing the empirical risk while maximizing the consistency of the manifold structure of data with the classifier. In addition, a distribution adaptation term is incorporated into the learning procedure of the classifier to lessen the distance between two domains by minimizing it. The validity of the proposed technique is tested on different image categorization datasets and the experimental results demonstrate that it performs well compared to the state-of-the-art methods.

BackgroundMechanisms underlying blood pressure (BP) changes in obstructive sleep apnoea (OSA) are incompletely understood. We assessed the associations between BP and selected polysomnography (PSG) traits: sleep depth, airflow limitation measurements and OSA-specific hypoxic burden.MethodsThis cross-sectional analysis included 2055 participants from the Multi-Ethnic Study of Atherosclerosis who underwent PSG and BP measurements in 2010–2013. Sleep depth was assessed using the ‘OR product’, a continuous measure of arousability. Airflow limitation was assessed by duty cycle (Ti/Tt) and % of breaths with flow limitation, and hypoxia by ‘hypoxic burden’. Primary outcomes were medication-adjusted systolic BP (SBP) and diastolic BP (DBP). We used generalised linear models adjusted for age, sex, race/ethnicity, smoking, education, body mass index, alcohol use, periodic limb movements and alternative physiological disturbances.ResultsThe sample had a mean age of 68.4 years and apnoea–hypopnoea index of 14.8 events/hour. Sleep depth was not significantly associated with BP. Every 1 SD increment in log-transformed non-rapid eye movement duty cycle was associated with 0.9% decrease in SBP (95% CI: 0.1% to 1.6%), even after adjusting for sleep depth and hypoxic burden. Every 1 SD increment in log-transformed hypoxic burden was associated with a 1.1% increase in SBP (95% CI: 0.1% to 2.1%) and 1.9% increase in DBP (95% CI: 1.0% to 2.8%) among those not using hypertension medications.ConclusionsHigher duty cycle was associated with lower SBP overall and hypoxic burden with higher SBP and DBP among non-BP medication users. These findings suggest changes in both respiratory effort and oxygenation during sleep influence BP.

Introduction: One of the important factors for behavioral changes in chronic patients, especially cardiac patients, is the increased self-efficacy of these patients. The aim of this study was to determine correlation between defenses mechanism and self-efficacy in Ischemic Heart patient’s referred to Feiz hospital of Isfahan in 2017. Methods: This study was a correlational analytical study that consisted of all Ischemic Heart patient’s referred to Feiz hospital of Esfahan in second half of 2017. Based on inclusion criteria and census sampling, 150 patients were included. To collect data we used three questionnaires: demographic, Defense Styles Questionnaire-DSQ and Sullivan’s cardiac self-efficacy questionnaire. Data was analyzed using SPSS 19, Kolmogorov–Smirnov test, independent t-test, and Pearson correlation coefficients. Results: Based on the results, 53.3% of patients were male, 76% of whom were married and 32% had undergraduate education. Findings showed the rate of defense mechanisms with a mean of 193.07±28.45 and their self-efficacy with a moderate mean. Pearson correlation coefficient showed that there is a positive and significant correlation between the developed defense mechanisms with self-efficacy of patients (r=0.20, P=0.013). Conclusion: The results of the study indicated that there is a positive and significant relationship between using defense mechanisms and predicting the self-efficacy of patients with ischemic heart; that means by using grown defense mechanisms, the self-efficacy will upgrade. So training and enhancement of developed mechanisms and reduction of unhealthy mechanisms by nurses is suggested.

The recent discovery that a combination of noradrenergic and antimuscarinic drugs improved upper airway muscle function during sleep and reduced OSA severity has revitalized interest in pharmacologic therapies for OSA.Would 1 week of reboxetine plus oxybutynin (Reb-Oxy) be effective on OSA severity?A randomized, placebo-controlled, double-blind, crossover trial was performed comparing 4 mg reboxetine plus 5 mg oxybutynin (Reb-Oxy) vs placebo in patients with OSA. After a baseline in-laboratory polysomnogram (PSG), patients underwent PSGs after 7 nights of Reb-Oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI), which was the primary outcome. Response rate was based on the percentage of subjects with a ≥ 50% reduction in AHI from baseline. Secondary outcomes included Epworth Sleepiness Scale (ESS) score and psychomotor vigilance test (PVT) values. Home oximetry evaluated overnight oxygen desaturation index (ODI) throughout treatment.Sixteen subjects aged 57 [51-61] years (median [interquartile range]) with a BMI of 30 [26-36] kg/mThe administration of Reb-Oxy greatly decreased OSA severity and increased vigilance. These results highlight potential possibilities for pharmacologic treatment of OSA.ClinicalTrials.gov; No.: NCT04449133; URL: www.clinicaltrials.gov.

Introduction Flow limitation is the distinguishing characteristic of obstructive sleep apnoea. Critically, periods of flow limitation can occur without overt reductions in airflow (e.g. disproportionate increase in ventilatory drive vs. achieved ventilation), however, such periods are ignored by clinical scoring. Here we investigate flow limitation during so-called “stable breathing”, i.e. periods of sleep without scored events, by applying our recently-validated model to estimate flow limitation from the airflow signal. Methods Flow limitation was visually-scored (N=117,871 breaths) from N=40 participants attending an overnight sleep study for suspected sleep apnoea. Scoring was aided by physiological signals (e.g. intra-oesophageal diaphragm EMG). Model flow limitation classification used features extracted from the pneumotach signal (cross-validated accuracy=92.4%). We applied this method to investigate the occurrence of flow limitation during stable breathing, defined as periods of sleep >3 min duration without scored arousals or respiratory events. Results Model predicted flow limitation frequency was strongly correlated with visual scoring (R²=0.84 p Discussion Flow limitation occurs surprisingly frequently during stable breathing. While some individuals achieve stable breathing with minimal flow limitation, others demonstrate substantial flow limitation. Heterogeneity in frequency of flow limitation (within and between individuals) may provide further insights into emergent phenotypic variability within sleep disordered breathing. Finally, this model performed similarly in nasal pressure (88.2% accuracy), indicating potential application to clinical studies.

Study Objectives New electroencephalogram (EEG) features became available for use in polysomnography and have shown promise in early studies. They include a continuous index of sleep depth (odds-ratio-product: ORP), agreement between right and left sleep depth (R/L coefficient), dynamics of sleep recovery following arousals (ORP-9), general EEG amplification (EEG Power), alpha intrusion and arousal intensity. This study was undertaken to establish ranges and reproducibility of these features in subjects with different demographics and clinical status. Methods We utilized data from the two phases of the Sleep-Heart-Health-Study (SHHS1 and SHHS2). Polysomnograms of 5,804 subjects from SHHS1 were scored to determine the above features. Feature values were segregated according to clinical status of obstructive sleep apnea (OSA), insomnia, insomnia plus OSA, no clinical sleep disorder, and demographics (age, gender, and race). Results from SHHS visit2 were compared with SHHS1 results. Results All features varied widely among clinical groups and demographics. Relative to participants with no sleep disorder, wake ORP was higher in participants reporting insomnia symptoms and lower in those with OSA (p < 0.0001 for both), reflecting opposite changes in sleep pressure, while NREM ORP was higher in both insomnia and OSA (p 0.75). Conclusions The reported results serve as bases for interpreting studies that utilize novel sleep EEG biomarkers and identify characteristic EEG changes that vary with age, gender and may help distinguish insomnia from OSA.