Dysregulation of the Long Noncoding RNA X-Inactive-Specific Transcript Expression in Male Patients with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a sex-biased disease with female gender as a significant risk factor. Recently, we reported that increased expression of the long noncoding RNA X-inactive-specific transcript (Xist), as induced by an intersectin-1s protein fragment with proliferative potential (EHITSN), may explain the sexual dimorphism of female pulmonary artery endothelial cells (ECs) and at least in part, the imbalance sex/ratio of PAH. Xist is essential for X-chromosome inactivation and dosage compensation of X-linked genes. Increased Xist expression was also detected in a subset of ECs and lung tissue samples of male patients with PAH. The role of different Xist expression levels in ECs of male patients with PAH (ECPAH) was studied in several lines of male ECPAH in conjunction with molecular, biochemical, morphologic, and functional approaches. Male ECPAH showed on average 10.3-fold increase in high Xist versus low Xist, a significant association between Xist levels and their proliferative potential, and a heterogeneous methylation of the Xist/Tsix locus. Interestingly, Xist up-regulation in male ECPAH decreases the expression of Klf2, via EHITSN interaction with EZH2, the catalytic subunit of the polycomb repressive complex 2. Moreover, the studies demonstrate that EHITSN-triggered p38/Elk1/c-Fos signaling is a pathologic mechanism central to ECPAH proliferation and the dynamic crosstalk with cell cycle regulatory proteins cyclin A1/cyclin D2 and Xist-EZH2-Klf2 interaction participate directly and differentially in establishing the proliferative profile of male ECPAH.

Senolytic-facilitated Reversal of End-Organ Dysfunction in a Murine Model of Obstructive Sleep Apnea.

Rationale: Obstructive sleep apnea (OSA) is a highly prevalent condition that is associated with accelerated biological aging and multiple end-organ morbidities. Current treatments, such as continuous positive airway pressure (CPAP), have shown limited cognitive, metabolic, and cardiovascular beneficial outcomes despite adherence. Thus, adjunct therapies aiming to reduce OSA burden, such as senolytics, could improve OSA outcomes.Objectives: To assess if targeting senescence in addition to partial normoxia mimicking "good" CPAP adherence can improve physiological outcomes in mice exposed to chronic intermittent hypoxia.Methods: We compared the effects of 6 weeks of therapy with either partial normoxic recovery alone or combined with the senolytic navitoclax after 16 weeks of intermittent hypoxia exposures, a hallmark of OSA, on multiphenotypic cardiometabolic and neurocognitive parameters.Measurements and Main Results: Our findings indicate that only when combined with navitoclax, partial normoxic recovery significantly improved sleepiness (sleep in the dark phase: 34% ± 4% vs. 26% ± 3%; P < 0.01), cognition (preference score: 51% ± 19% vs. 70% ± 11%; P = 0.048), coronary artery function (response to acetylcholine [vasodilation]: 56% ± 13% vs. 72% ± 10%; P < 0.001), glucose, and lipid metabolism and reduced intestinal permeability and senescence in multiple organs.Conclusions: These findings indicate that the reversibility of end-organ morbidities induced by OSA is not only contingent on restoration of normal oxygenation patterns but can be further enhanced by targeting other OSA-mediated detrimental cellular processes, such as accelerated senescence.

Physicians prescribe fewer analgesics during night shifts than day shifts.

Adequate pain management is one of the biggest challenges of the modern healthcare system. Physician perception of patient subjective pain, which is crucial to pain management, is susceptible to a host of potential biases. Here we explore the timing of physicians' work as a previously unrecognized source of systematic bias in pain management. We hypothesized that during night shifts, sleep deprivation, fatigue, and stress would reduce physicians' empathy for others' pain, leading to underprescription of analgesics for patient pain relief. In study 1, 67 resident physicians, either following a night shift or not, performed empathy for pain assessment tasks and simulated patient scenarios in laboratory conditions. As predicted, following a night shift, physicians showed reduced empathy for pain. In study 2, we explored this phenomenon in medical decisions in the field. We analyzed three emergency department datasets from Israel and the United States that included discharge notes of patients arriving with pain complaints during 2013 to 2020 (n = 13,482). Across all datasets, physicians were less likely to prescribe an analgesic during night shifts (compared to daytime shifts) and prescribed fewer analgesics than generally recommended by the World Health Organization. This effect remained significant after adjusting for patient, physician, type of complaint, and emergency department characteristics. Underprescription for pain during night shifts was particularly prominent for opioids. We conclude that night shift work is an important and previously unrecognized source of bias in pain management, likely stemming from impaired perception of pain. We consider the implications for hospitals and other organizations employing night shifts.

Chronic intermittent hypoxia remodels catecholaminergic nerve innervation in mouse atria.

Chronic intermittent hypoxia (CIH, a model for sleep apnoea) is a major risk factor for several cardiovascular diseases. Autonomic imbalance (sympathetic overactivity and parasympathetic withdrawal) has emerged as a causal contributor of CIH-induced cardiovascular disease. Previously, we showed that CIH remodels the parasympathetic pathway. However, whether CIH induces remodelling of the cardiac sympathetic innervation remains unknown. Mice (male, C57BL/6J, 2-3 months) were exposed to either room air (RA, 21% O2 ) or CIH (alternating 21% and 5.7% O2 , every 6 min, 10 h day-1 ) for 8-10 weeks. Flat-mounts of their left and right atria were immunohistochemically labelled for tyrosine hydroxylase (TH, a sympathetic marker). Using a confocal microscope (or fluorescence microscope) and Neurlocudia 360 digitization and tracing system, we scanned both the left and right atria and quantitatively analysed the sympathetic axon density in both groups. The segmentation data was mapped onto a 3D mouse heart scaffold. Our findings indicated that CIH significantly remodelled the TH immunoreactive (-IR) innervation of the atria by increasing its density at the sinoatrial node, the auricles and the major veins attached to the atria (P < 0.05, n = 7). Additionally, CIH increased the branching points of TH-IR axons and decreased the distance between varicosities. Abnormal patterns of TH-IR axons around intrinsic cardiac ganglia were also found following CIH. We postulate that the increased sympathetic innervation may further amplify the effects of enhanced CIH-induced central sympathetic drive to the heart. Our work provides an anatomical foundation for the understanding of CIH-induced autonomic imbalance. KEY POINTS: Chronic intermittent hypoxia (CIH, a model for sleep apnoea) causes sympathetic overactivity, cardiovascular remodelling and hypertension. We determined the effect of CIH on sympathetic innervation of the mouse atria. In vivo CIH for 8-10 weeks resulted in an aberrant axonal pattern around the principal neurons within intrinsic cardiac ganglia and an increase in the density, branching point, tortuosity of catecholaminergic axons and atrial wall thickness. Utilizing mapping tool available from NIH (SPARC) Program, the topographical distribution of the catecholaminergic innervation of the atria were integrated into a novel 3D heart scaffold for precise anatomical distribution and holistic quantitative comparison between normal and CIH mice. This work provides a unique neuroanatomical understanding of the pathophysiology of CIH-induced autonomic remodelling.

Prevalence and factors associated with digital addiction among students taking university entrance tests: a GIS-based study.

BACKGROUND: The surge in digital media consumption, coupled with the ensuing consequences of digital addiction, has witnessed a rapid increase, particularly after the initiation of the COVID-19 pandemic. Despite some studies exploring specific technological addictions, such as internet or social media addiction, in Bangladesh, there is a noticeable gap in research focusing on digital addiction in a broader context. Thus, this study aims to investigate digital addiction among students taking the university entrance test, examining its prevalence, contributing factors, and geographical distribution using GIS techniques. METHODS: Data from a cross-sectional survey were collected from a total of 2,157 students who were taking the university entrance test at Jahangirnagar University, Bangladesh. A convenience sampling method was applied for data collection using a structured questionnaire. Statistical analyses were performed with SPSS 25 Version and AMOS 23 Version, whereas ArcGIS 10.8 Version was used for the geographical distribution of digital addiction. RESULTS: The prevalence of digital addiction was 33.1% (mean score: 16.05 ± 5.58). Those students who are attempting the test for a second time were more likely to be addicted (42.7% vs. 39.1%), but the difference was not statistically significant. Besides, the potential factors predicted for digital addiction were student status, satisfaction with previous mock tests, average monthly expenditure during the admission test preparation, and depression. No significant difference was found between digital addiction and districts. However, digital addiction was higher in the districts of Manikganj, Rajbari, Shariatpur, and Chittagong Hill Tract areas, including Rangamati, and Bandarban. CONCLUSIONS: The study emphasizes the pressing need for collaborative efforts involving educational policymakers, institutions, and parents to address the growing digital addiction among university-bound students. The recommendations focus on promoting alternative activities, enhancing digital literacy, and imposing restrictions on digital device use, which are crucial steps toward fostering a healthier digital environment and balanced relationship with technology for students.

Cancer-related Fatigue in Lung Cancer: A Research Agenda: An Official American Thoracic Society Research Statement.

Background: Fatigue is the most common symptom among cancer survivors. Cancer-related fatigue (CRF) may occur at any point in the cancer care continuum. Multiple factors contribute to CRF development and severity, including cancer type, treatments, presence of other symptoms, comorbidities, and medication side effects. Clinically, increasing physical activity, enhancing sleep quality, and recognizing sleep disorders are integral to managing CRF. Unfortunately, CRF is infrequently recognized, evaluated, or treated in lung cancer survivors despite more frequent and severe symptoms than in other cancers. Therefore, increased awareness and understanding of CRF are needed to improve health-related quality of life in lung cancer survivors. Objectives: 1) To identify and prioritize knowledge and research gaps and 2) to develop and prioritize research questions to evaluate mechanistic, diagnostic, and therapeutic approaches to CRF among lung cancer survivors. Methods: We convened a multidisciplinary panel to review the available literature on CRF, focusing on the impacts of physical activity, rehabilitation, and sleep disturbances in lung cancer. We used a three-round modified Delphi process to prioritize research questions. Results: This statement identifies knowledge gaps in the 1) detection and diagnostic evaluation of CRF in lung cancer survivors; 2) timing, goals, and implementation of physical activity and rehabilitation; and 3) evaluation and treatment of sleep disturbances and disorders to reduce CRF. Finally, we present the panel's initial 32 research questions and seven final prioritized questions. Conclusions: This statement offers a prioritized research agenda to 1) advance clinical and research efforts and 2) increase awareness of CRF in lung cancer survivors.

Single-cell RNA-seq uncovers cellular heterogeneity and provides a signature for paediatric sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a highly prevalent disease and a major cause of systemic inflammation leading to neurocognitive, behavioural, metabolic and cardiovascular dysfunction in children and adults. However, the impact of OSA on the heterogeneity of circulating immune cells remains to be determined. METHODS: We applied single-cell transcriptomics analysis (scRNA-seq) to identify OSA-induced changes in transcriptional landscape in peripheral blood mononuclear cell (PBMC) composition, which uncovered severity-dependent differences in several cell lineages. Furthermore, a machine-learning approach was used to combine scRNAs-seq cell-specific markers with those differentially expressed in OSA. RESULTS: scRNA-seq demonstrated OSA-induced heterogeneity in cellular composition and enabled the identification of previously undescribed cell types in PBMCs. We identified a molecular signature consisting of 32 genes, which distinguished OSA patients from various controls with high precision (area under the curve 0.96) and accuracy (93% positive predictive value and 95% negative predictive value) in an independent PBMC bulk RNA expression dataset. CONCLUSION: OSA deregulates systemic immune function and displays a molecular signature that can be assessed in standard cellular RNA without the need for pre-analytical cell separation, thereby making the assay amenable to application in a molecular diagnostic setting.

Gut microbiota mediate vascular dysfunction in a murine model of sleep apnoea: effect of probiotics.

BACKGROUND: Obstructive sleep apnoea (OSA) is a chronic prevalent condition characterised by intermittent hypoxia (IH), and is associated with endothelial dysfunction and coronary artery disease (CAD). OSA can induce major changes in gut microbiome diversity and composition, which in turn may induce the emergence of OSA-associated morbidities. However, the causal effects of IH-induced gut microbiome changes on the vasculature remain unexplored. Our objective was to assess if vascular dysfunction induced by IH is mediated through gut microbiome changes. METHODS: Faecal microbiota transplantation (FMT) was conducted on C57BL/6J naïve mice for 6 weeks to receive either IH or room air (RA) faecal slurry with or without probiotics (VSL#3). In addition to 16S rRNA amplicon sequencing of their gut microbiome, FMT recipients underwent arterial blood pressure and coronary artery and aorta function testing, and their trimethylamine N-oxide (TMAO) and plasma acetate levels were determined. Finally, C57BL/6J mice were exposed to IH, IH treated with VSL#3 or RA for 6 weeks, and arterial blood pressure and coronary artery function assessed. RESULTS: Gut microbiome taxonomic profiles correctly segregated IH from RA in FMT mice and the normalising effect of probiotics emerged. Furthermore, IH-FMT mice exhibited increased arterial blood pressure and TMAO levels, and impairments in aortic and coronary artery function (p<0.05) that were abrogated by probiotic administration. Lastly, treatment with VSL#3 under IH conditions did not attenuate elevations in arterial blood pressure or CAD. CONCLUSIONS: Gut microbiome alterations induced by chronic IH underlie, at least partially, the typical cardiovascular disturbances of sleep apnoea and can be mitigated by concurrent administration of probiotics.

Obstructive sleep apnoea is related to melanoma aggressiveness through paraspeckle protein-1 upregulation.

BACKGROUND: In patients with obstructive sleep apnoea (OSA), intermittent hypoxia induces overexpression of paraspeckle component (PSPC)1, a master modulator of transforming growth factor (TGF)-ß signalling, which promotes cell cancer progression through epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of intermittent hypoxia-induced effects on PSPC1, and their consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma with or without OSA, and their relationship with tumour aggressiveness along with the in vitro effects of soluble PSPC1 and intermittent hypoxia on melanoma cell aggressiveness mechanisms were assessed. METHODS: In 292 cutaneous melanoma patients, sleep studies and serum levels of PSPC1 and TGF-ß were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and intermittent hypoxia conditions. RESULTS: PSPC1 levels were higher in patients with moderate-severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several cutaneous melanoma clinical aggressiveness indicators. Both intermittent hypoxia exposures and serum from OSA patients upregulated TGF-ß expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics. CONCLUSION: In cutaneous melanoma patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with intermittent hypoxia would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.

Validation of a predictive model for obstructive sleep apnea in people with Down syndrome.

Detecting obstructive sleep apnea (OSA) is important to both prevent significant comorbidities in people with Down syndrome (DS) and untangle contributions to other behavioral and mental health diagnoses. However, laboratory-based polysomnograms are often poorly tolerated, unavailable, or not covered by health insurance for this population. In previous work, our team developed a prediction model that seemed to hold promise in identifying which people with DS might not have significant apnea and, consequently, might be able to forgo a diagnostic polysomnogram. In this study, we sought to validate these findings in a novel set of participants with DS. We recruited an additional 64 participants with DS, ages 3-35 years. Caregivers completed the same validated questionnaires, and our study team collected vital signs, physical exam findings, and medical histories that were previously shown to be predictive. Patients then had a laboratory-based polysomnogram. The best modeling had a validated negative predictive value of 50% for an apnea-hypopnea index (AHI) > 1/hTST and 73.7% for AHI >5/hTST. The positive predictive values were 60% and 39.1%, respectively. As such, a clinically reliable screening tool for OSA in people with DS was not achieved. Patients with DS should continue to be monitored for OSA according to current healthcare guidelines.

Comorbid insomnia and sleep apnea in children: a preliminary explorative study.

Insomnia and sleep-disordered breathing (SDB) are prevalent sleep disorders. These disorders can therefore be concurrently present - comorbid insomnia and sleep apnea (COMISA). The prevalence of COMISA in the paediatric age range is unclear. As such, phenotypic constructs should help better define this comorbid condition if it exists in children and improve both diagnostic sensitivity and ultimately clinical care outcomes. We aimed to evaluate the frequency of insomnia in children and adolescents referred for evaluation of sleep symptoms suggestive of SDB in one initial (Cohort#1) and verify such findings in an independent cohort (Cohort#2) using a retrospective cross-sectional approach in patients aged 9-19 years presenting at a sleep centre to be evaluated for symptoms of SDB. Cohort #1 comprised 50 consecutive children (58% males; mean [SD] age 13.6 [3.3] years; median [interquartile range, IQR] Epworth Sleepiness Scale score 10 [6-12]) who were evaluated using validated SDB and insomnia questionnaires. Cohort#2 was extracted from electronic medical records and included 384 polysomnographically evaluated children (mean [SD] age 12.9 [3.6] years; mean [SD] body mass index z score 1.27 [0.28]; median Epworth Sleepiness Scale score 9.7 [4-17]). In Cohort #1, 56% were at high risk of SDB, 36% had insomnia alone, and 18% were at high risk of COMISA. The prevalence of COMISA in Cohort #2 was 16%, 72% had SDB alone, and 12% had insomnia alone. In both cohorts, COMISA manifested as increased propensity for sleepiness and fatigue during both waking and daytime. Thus, the presence of COMISA is frequent in the paediatric age range and accompanied by a more prominent symptomatic phenotype.

Nocturnal oximetry parameters as predictors of sleep apnea severity in resource-limited settings.

Nocturnal oximetry is an alternative modality for evaluating obstructive sleep apnea syndrome (OSAS) severity when polysomnography is not available. The Oxygen Desaturation (≥3%) Index (ODI3) and McGill Oximetry Score (MOS) are used as predictors of moderate-to-severe OSAS (apnea-hypopnea index-AHI >5 episodes/h), an indication for adenotonsillectomy. We hypothesised that ODI3 is a better predictive parameter for AHI >5 episodes/h than the MOS. All polysomnograms performed in otherwise healthy, snoring children with tonsillar hypertrophy in a tertiary hospital (November 2014 to May 2019) were analysed. The ODI3 and MOS were derived from the oximetry channel of each polysomnogram. Logistic regression was applied to assess associations of ODI3 or MOS (predictors) with an AHI >5 episodes/h (primary outcome). Receiver operating characteristic (ROC) curves and areas under ROC curves were used to compare the ODI3 and MOS as predictors of moderate-to-severe OSAS. The optimal cut-off value for each oximetry parameter was determined using Youden's index. Polysomnograms of 112 children (median [interquartile range] age 6.1 [3.9-9.1] years; 35.7% overweight) were analysed. Moderate-to-severe OSAS prevalence was 49.1%. The ODI3 and MOS were significant predictors of moderate-to-severe OSAS after adjustment for overweight, sex, and age (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.19-1.51); and OR 4.10, 95% CI 2.06-8.15, respectively; p < 0.001 for both). Area under the ROC curve was higher for the ODI3 than for MOS (0.903 [95% CI 0.842-0.964] versus 0.745 [95% CI 0.668-0.821]; p < 0.001). Optimal cut-off values for the ODI3 and MOS were ≥4.3 episodes/h and ≥2, respectively. The ODI3 emerges as preferable or at least a complementary oximetry parameter to MOS for detecting moderate-to-severe OSAS in snoring children when polysomnography is not available.

Adaptation and validation of the Chinese version of the Sleep Quality Questionnaire.

STUDY OBJECTIVES: Sleep quality is essential to health. The current study aimed to adapt and validate the Sleep Quality Questionnaire (SQQ) into Chinese language. METHODS: The Chinese version of the SQQ (SQQ-C) was created following the guidelines for cross-cultural adaptation. Compliant with the COSMIN methodology, baseline data (N = 13,325) examined three validity domains and internal consistency, including content validity using the content validity index (CVI) and the cognitive debriefing and focus group (relevance, comprehensiveness and comprehensibility), construct validity using structural validity and cross­sectional measurement invariance, and criterion validity using concurrent/convergent validity. Follow-up data (N = 3410) gathered within a mean of 168 (167-207) h interval were used to additionally assess longitudinal measurement invariance and test-retest reliability using intraclass correlation coefficient (ICC). RESULTS: Scale-level CVI/Average was equal to 0.922; Item-level CVIs ranged from 0.889 to 1.000 (excellent), except for item 2 (0.556-fair). A panel of local experts and local participants during cognitive debriefing and focus group stated that it had sufficient relevance and comprehensibility but a slight deficiency in comprehensiveness. Confirmatory factor analysis indicated a stable two-factor structure encompassing Daytime Sleepiness Subscale and Sleep Difficulty Subscale from baseline to follow-up data. The SQQ-C-9 (without item 2) outperformed the SQQ-C-10 (full form). The SQQ-C-9 provided evidence of measurement invariance (strict) across subgroups (cohorts, gender, and age) and across time. The SQQ-C was negatively correlated with the Chinese Nonrestorative Sleep Scale and the Chinese Sleep Condition Indicator. Cronbach's alpha (α), McDonald's Omega (ω), and ICC, respectively, ranged from 0.712 to 0.838, 0.723 to 0.840, and 0.738 to 0.764 for total scale and each subscale. CONCLUSION: The SQQ-C exhibits adequate psychometric properties and a stable two-factor structure, and should enable valuable assessments of sleep quality in clinical and research settings.

Depression among Bangladeshi diabetic patients: a cross-sectional, systematic review, and meta-analysis study.

AIM: This study aims to assess the prevalence and associated factors of depression among diabetic patients in a cross-sectional sample and perform a systematic review and meta-analysis of the extant studies to date. METHODS: A face-to-face semi-structured interview of established diabetic patients was conducted in four districts of Bangladesh between May 24 to June 24, 2022, and the Patient Health Questionnaire (PHQ-2) was used to detect depression. PRISMA guidelines were followed to conduct a systematic review and meta-analysis, with Bangladeshi articles published until 3rd February 2023. RESULTS: The prevalence of depression among 390 diabetic patients was 25.9%. Having secondary education and using both insulin and medication increased the likelihood of depression, whereas being a business professional and being physically active reduced the likelihood of depression. The systematic review and meta-analysis indicated that the pooled estimated prevalence of depression was 42% (95% CI 32-52%). Females had a 1.12-times higher risk of depression than males (OR = 1.12, 95% CI: 0.99 to 1.25, p < 0.001). CONCLUSIONS: Two-fifths of diabetic patients were depressed, with females at higher risk. Since depression among diabetic patients increases adverse outcomes, improved awareness and screening methods should be implemented to detect and treat depression in diabetic patients.

Predictive factors for obstructive sleep apnea in adults with severe asthma receiving biologics: a single-center cross-sectional study.

PURPOSE: To evaluate the prevalence and potential predictors of obstructive sleep apnea (OSA) in a cohort of adults with severe asthma. METHODS: From March 2021 to December 2021, this cross-sectional study enrolled patients with severe asthma receiving biologics, who were consecutively referred for sleep evaluation irrespective of sleep-related symptoms. Clinical and functional data, including three OSA screening instruments (GOAL, STOP-Bang, and NoSAS) were recorded. All participants underwent a portable sleep test (ApneaLink Air™). OSA diagnosis was based on the respiratory disturbance index ≥ 5.0/h and subclassified according to severity thresholds. Data were subjected to logistic regression tests to identify possible predictors for OSA. Discrimination was estimated from the area under the curve (AUC). RESULTS: Overall, 56 outpatients were included (80% females): 54% with any OSA, 13% with moderate-to-severe OSA, and 4% with severe OSA. In the multivariate analysis, no parameter emerged as an independent predictor for OSA: age (p = 0.080), body mass index (p = 0.060), loud snoring (p = 0.130), and hypertension (p = 0.848). No screening instrument was useful to predict any OSA: GOAL (AUC: 0.714; 95% confidence interval (CI): 0.579-0.849), NoSAS (AUC: 0.645; 95% CI: 0.497-0.793), and STOP-Bang (AUC: 0.640; 95% CI: 0.493-0.788). Similarly, no screening tool was also useful for predicting moderate-to-severe OSA or severe OSA. CONCLUSION: Patients with evere asthma receiving biologics exhibit a high prevalence of OSA. However, no clinical, functional, or OSA screening instrument showed acceptable discriminatory ability to predict the presence of OSA in these patients with severe asthma.

Snoring, obstructive sleep apnea, and upper respiratory tract infection in elementary school children in Japan.

PURPOSE: Both obstructive sleep apnea (OSA) and the common cold are disorders of the upper respiratory tract, and may be associated. However, studies on the association between OSA and upper respiratory tract infections (URTI) in children are scarce. The aim of this study was to investigate possible associations between snoring, the severity of OSA, and URTI in elementary school children. METHODS: This was a cross-sectional study in a community cohort of elementary school children (first and second graders) in Japan. Information on sleep habits, history of URTI, and OSA risk was obtained from a parental questionnaire. Children underwent overnight tracheal sound recordings from which apnea-hypopnea index was estimated. Multivariable logistic analysis was employed to define the association between snoring, OSA, and URTI ≥ 3 episodes over six months. RESULTS: Of the 922 potential enrollees, 653 children and their parents (71%) agreed to participate in the study. Multivariable-adjusted ORs for URTI were 1.73 (95%CI: 1.16 to 2.59) in children who snored 1 to 4 nights per week and 2.82 (95%CI: 1.26 to 6.28) in snoring ≥ 5 nights per week compared with never snoring (reference). Likewise, subjectively reported louder snoring, as well as objectively defined louder sound levels, were significantly associated with URTI. In addition, OR for URTI in children with an estimated apnea-hypopnea index ≥ 2.0 events/hour was 2.65 (95%CI: 1.32 to 5.31) compared to children with apnea-hypopnea index less than 1.0 events/hour (reference). CONCLUSIONS: Snoring and severity of OSA as measured by nocturnal tracheal sound recordings were associated with increased susceptibility to URTI in elementary school children.

Sleep hygiene behaviours mediate the association between health/e-health literacy and mental wellbeing.

BACKGROUND: Health literacy and e-health literacy are important factors helping people shape awareness of health behaviours in different aspects, including sleep hygiene behaviours. Good sleep hygiene behaviours promote sleep quality and are beneficial to overall mental wellbeing. OBJECTIVE: We aimed to examine if sleep hygiene behaviours may mediate the association between health literacy/e-health literacy and mental wellbeing. METHODS: Adult Iranian subjects (n = 9775; mean [SD] age = 36.44 [11.97] years; 67.3% females) completed the Health Literacy Instrument for Adults, eHealth Literacy Scale, three items on sleep hygiene behaviour that have been used in prior research and the Short Warwick Edinburgh Mental Wellbeing Scale. Data were then subjected to structural equation modelling (SEM) including 500 bootstrapping resampling to examine whether sleep hygiene is a mediator in the relationship between health literacy/e-health literacy and mental wellbeing. FINDINGS: Both health literacy and e-health literacy were significantly associated with mental wellbeing (r = .63 for health literacy and .39 for e-health literacy; p < .001) and sleep hygiene behaviours (r = .58 for health literacy and .36 for e-health literacy; p < .001). Sleep hygiene behaviours were significantly associated with mental wellbeing (r = .42; p < .001). Moreover, SEM that incorporated bootstrapping approaches indicated that sleep hygiene behaviours were significant mediators in the association between health literacy/e-health literacy and mental wellbeing. CONCLUSIONS: We conclude that health literacy and e-health literacy are associated with mental health wellbeing in the Iranian population. Additionally, the association could be mediated via sleep hygiene behaviours. PATIENT OR PUBLIC CONTRIBUTION: The study was co-designed with healthcare providers from the vice-Chancellor's Office for Health Affairs of Qazvin University of Medical Sciences as equal partners. Moreover, the women's health volunteers were involved in the design of the study.

Clinical and polysomnographic predictors of suboptimal auto-adjusting CPAP titration in adult OSA patients: a single-center study.

PURPOSE: To examine potential clinical, demographic, anthropometric, and polysomnographic predictors of successful auto-adjusting continuous positive airway pressure (CPAP) titration for treatment of obstructive sleep apnea (OSA). METHODS: This cross-sectional study was conducted in adults diagnosed with moderate-to-severe OSA (baseline apnea-hypopnea index [AHI] ≥ 15.0/h), who underwent auto-adjusting CPAP titration (S9 or S10 AutoSet ResMed®) in a sleep laboratory setting while wearing a nasal or pillow mask. Participants were then grouped into two groups: optimal CPAP titration (residual AHI < 5.0/h) or suboptimal CPAP titration (residual AHI ≥ 5.0/h). Multivariate logistic regression analysis was used to assess possible independent predictive factors for suboptimal CPAP titration. RESULTS: A total of 1222 adults consisting of 874 subjects with optimal CPAP titration (71.5%) and 348 subjects with suboptimal CPAP titration (28.5%) were evaluated. Multivariate analysis resulted in a model with an adequate calibration (Hosmer-Lemeshow chi-square-test: 7.088; p = 0.527), with male sex, higher values of baseline AHI, therapeutic pressure (95th percentile), and mask leak (95th percentile) emerging as significant and independent predictors for suboptimal CPAP titration: adjusted odds ratio (OR): 1.456 (95% confidence interval [CI] 1.076-1.971; p = 0.015), OR: 1.009 (95% CI 1.002-1.016; p = 0.013), OR: 1.281 (95% CI 1.206-1.361; p < 0.001), and 1.035 (1.026-1.043; p < 0.001), respectively. CONCLUSIONS: In a large cohort of adults undergoing auto-adjusting CPAP titration due to moderate-to-severe OSA, male sex, increased values of baseline AHI, pressure requirements, and mask leak were significant predictors for less than optimal CPAP titration.

Cardiovascular Disease in Obstructive Sleep Apnea: Putative Contributions of Mineralocorticoid Receptors.

Obstructive sleep apnea (OSA) is a chronic and highly prevalent condition that is associated with oxidative stress, inflammation, and fibrosis, leading to endothelial dysfunction, arterial stiffness, and vascular insulin resistance, resulting in increased cardiovascular disease and overall mortality rates. To date, OSA remains vastly underdiagnosed and undertreated, with conventional treatments yielding relatively discouraging results for improving cardiovascular outcomes in OSA patients. As such, a better mechanistic understanding of OSA-associated cardiovascular disease (CVD) and the development of novel adjuvant therapeutic targets are critically needed. It is well-established that inappropriate mineralocorticoid receptor (MR) activation in cardiovascular tissues plays a causal role in a multitude of CVD states. Clinical studies and experimental models of OSA lead to increased secretion of the MR ligand aldosterone and excessive MR activation. Furthermore, MR activation has been associated with worsened OSA prognosis. Despite these documented relationships, there have been no studies exploring the causal involvement of MR signaling in OSA-associated CVD. Further, scarce clinical studies have exclusively assessed the beneficial role of MR antagonists for the treatment of systemic hypertension commonly associated with OSA. Here, we provide a comprehensive overview of overlapping mechanistic pathways recruited in the context of MR activation- and OSA-induced CVD and propose MR-targeted therapy as a potential avenue to abrogate the deleterious cardiovascular consequences of OSA.

Multi-Omics Analysis of Circulating Exosomes in Adherent Long-Term Treated OSA Patients.

Obstructive sleep apnea (OSA) is a highly prevalent chronic disease affecting nearly a billion people globally and increasing the risk of multi-organ morbidity and overall mortality. However, the mechanisms underlying such adverse outcomes remain incompletely delineated. Extracellular vesicles (exosomes) are secreted by most cells, are involved in both proximal and long-distance intercellular communication, and contribute toward homeostasis under physiological conditions. A multi-omics integrative assessment of plasma-derived exosomes from adult OSA patients prior to and after 1-year adherent CPAP treatment is lacking. We conducted multi-omic integrative assessments of plasma-derived exosomes from adult OSA patients prior to and following 1-year adherent CPAP treatment to identify potential specific disease candidates. Fasting morning plasma exosomes isolated from 12 adult patients with polysomnographically-diagnosed OSA were analyzed before and after 12 months of adherent CPAP therapy (mean ≥ 6 h/night) (OSAT). Exosomes were characterized by flow cytometry, transmission electron microscopy, and nanoparticle tracking analysis. Endothelial cell barrier integrity, wound healing, and tube formation were also performed. Multi-omics analysis for exosome cargos was integrated. Exosomes derived from OSAT improved endothelial permeability and dysfunction as well as significant improvement in tube formation compared with OSA. Multi-omic approaches for OSA circulating exosomes included lipidomic, proteomic, and small RNA (miRNAs) assessments. We found 30 differentially expressed proteins (DEPs), 72 lipids (DELs), and 13 miRNAs (DEMs). We found that the cholesterol metabolism (has04979) pathway is associated with lipid classes in OSA patients. Among the 12 subjects of OSA and OSAT, seven subjects had complete comprehensive exosome cargo information including lipids, proteins, and miRNAs. Multi-omic approaches identify potential signature biomarkers in plasma exosomes that are responsive to adherent OSA treatment. These differentially expressed molecules may also play a mechanistic role in OSA-induced morbidities and their reversibility. Our data suggest that a multi-omic integrative approach might be useful in understanding how exosomes function, their origin, and their potential clinical relevance, all of which merit future exploration in the context of relevant phenotypic variance. Developing an integrated molecular classification should lead to improved diagnostic classification, risk stratification, and patient management of OSA by assigning molecular disease-specific therapies.