Prevalence of obstructive sleep apnoea in REM behaviour disorder:response to continuous positive airway pressure therapy

Objectives: Rapid eye movement behaviour disorder (RBD) is a parasomnia in which there is loss of muscle atonia during rapid eye movement (REM) sleep, resulting in dream enactment. The aims of this study were to determine the prevalence of obstructive sleep apnoea (OSA) in RBD patients and determine whether continuous positive airway pressure (CPAP) therapy improved RBD symptoms in patients with concomitant RBD and OSA.Methods: A questionnaire was mailed to 120 patients identified from a tertiary sleep centre with RBD meeting full International Classification for Sleep Disorders-3 (ICSD-3) criteria. Patients were diagnosed as having OSA if they had an apnoea-hypopnea index (AHI) ≥ 5. The questionnaire focused on CPAP-use, compliance and complications. Standard statistical analysis was undertaken using SPSS (v.21, IBM).Results: One hundred and seven of the potential participants (89.2%) had an OSA diagnosis. Out of 72 who responded to the questionnaire, (60%) 27 patients were using CPAP therapy. CPAP therapy improved RBD symptoms in 45.8% of this group. Despite this positive response to treatment in nearly half of CPAP-users, there was no significant difference in subjective or objective CPAP compliance between those who reported RBD improvement and those who did not. Subjective compliance with CPAP was over-reported, with mean usage being 7.17 ± 1.7 h per night compared to objective mean compliance of 5.71 ± 1.7.Conclusions: OSA is a very common co-morbidity of RBD. CPAP therapy might improve self-reported RBD symptoms further, in addition to standard RBD treatment. However, further research into its topic is necessary.</p

COMRADES determines in vivo RNA structures and interactions.

The structural flexibility of RNA underlies fundamental biological processes, but there are no methods for exploring the multiple conformations adopted by RNAs in vivo. We developed cross-linking of matched RNAs and deep sequencing (COMRADES) for in-depth RNA conformation capture, and a pipeline for the retrieval of RNA structural ensembles. Using COMRADES, we determined the architecture of the Zika virus RNA genome inside cells, and identified multiple site-specific interactions with human noncoding RNAs.This work was supported by Cancer Research UK (C13474/A18583, C6946/A14492) and the Wellcome Trust (104640/Z/14/Z, 092096/Z/10/Z) to E.A.M. O.Z. was supported by the Human Frontier Science Program (HFSP, LT000558/2015), the European Molecular Biology Organization (EMBO, ALTF1622-2014), and the Blavatnik Family Foundation postdoctoral fellowship. G.K. and M.G. were supported by Wellcome Trust grant 207507 and UK Medical Research Council. A.T.L.L. and J.C.M. were supported by core funding from Cancer Research UK (award no. 17197 to JCM). J.C.M was also supported by core funding from EMBL. I.G. and L.W.M. were supported by the Wellcome Trust Senior Fellowship in Basic Biomedical Science to I.G. (207498/Z/17/Z). I.J.M., L.F.G. and J.S.-G. were supported by grants R01GM104475 and R01GM115649 from NIGMS. C.K.K was supported by City University of Hong Kong Projects 9610363 and 7200520, Croucher Foundation Project 9500030 and Hong Kong RGC Projects 9048103 and 9054020. C.-F.Q. was supported by the NSFC Excellent Young Scientist Fund 81522025 and the Newton Advanced Fellowship from the Academy of Medical Sciences, UK

0059 Disruption of Circadian Clock Proteins in Obstructive Sleep Apnea Patients

Abstract Introduction Circadian clocks are endogenous coordinators of 24-hour rhythm of behavioral and molecular processes in living organism. They are composed of set of genes, which function as activators - CLOCK and BMAL1, which through binding to regulatory elements containing E-boxes activate transcription of repressor proteins Period (PER1) and cryptochrome (CRY1). The aim of the study was to assess: CLOCK, BMAL1, PER1 and CRY1 in obstructive sleep apnea (OSA) patients. Methods The study included 20 individuals, who underwent PSG and based on apnea-hypopnea index (AHI) were divided into severe OSA group (n=10; AHI30; 90% male) and healthy control (n=10; AHI&amp;lt;5; 70% male). All participants had their peripheral blood collected in the evening (9:00-10:00 pm) before and in the morning (6:00-7:00 am) after the PSG. CLOCK, BMAL1, CRY1 and PER1 protein concertation measurements were performed using ELISA. Results Increased level of following proteins was observed in OSA group: evening CLOCK (p=0.037), morning CLOCK (p=0.019), morning BMAL1 (p=0.0.16), evening PER1 (p=0.004), morning PER1 (p=0.029) and evening CRY1 (p=0.035). Yet, no significant difference was found between morning and evening level of any of the proteins in OSA and control group. Additionally, morning level of activator proteins CLOCK and BMAL1 had positive correlation with AHI (p=0.022, R=0.510 and p=0.010, R=0.560, respectively) and desaturation index (p=0.209, R=0.487 and p=0.009, R=0.570, respectively), while for repressor proteins PER1 and CRY1 significant correlations were found with desaturation index in the evening (p=0.025, R=0.500 and p=0.048, R=0.448, respectively), AHI in REM stage (p=0.009, R=0.569 and p=0.027, R=0.495, respectively) and AHI (for PER1 only p=0.014, R=0.540). Conclusion OSA patients have increased level of circadian clock proteins that corelates with severity of the disease. Further research is needed into the disruption of circadian clock should in OSA patients and possible effect of OSA treatment on concentrations of these proteins should be investigated. Support The study was financed by Polish National Centre Grant no. 2018/31/N/NZ5/03931. </jats:sec

0170 Association of HIF-1 Alpha and Beta Subunits with Clock and BMAL1 Proteins in Obstructive Sleep Apnea Patients

Abstract Introduction Obstructive sleep apnea (OSA) is a chronic condition that is characterized by intermittent hypoxia. Key regulator of oxygen metabolism is hypoxia inducible factor (HIF), which consists of oxygen sensitive subunit and continuously produced subunit. Circadian clock is composed of set of genes, which function as activators - CLOCK and BMAL 1, who similarly to HIF are basic helix-loop-helix-PER-ARNT-SIM transcription factors. Therefore, the aim of the study was to assess the relationship between HIF-1alpha, HIF-1beta, CLOCK, BMAL1 and polysomnography (PSG) variables in healthy individuals and severe OSA patients. Methods The study included 20 individuals, who underwent PSG and based on apnea-hypopnea index (AHI) were divided into severe OSA group (n=10; AHI30; 90% male) and healthy control (n=10; AHI&amp;lt;5; 70% male). All participants had their peripheral blood collected in the evening (9:00-10:00 pm) before and in the morning (6:00-7:00 am) after the PSG. HIF-1alpha, HIF-1beta, CLOCK and BMAL1 protein concertation measurements were performed using ELISA. Results Significant difference was observed in the following protein measurements between study groups: evening and morning HIF-1 (p=0.020 and p=0.043, respectively), evening HIF-1alpha (p=0.047), evening and morning CLOCK (p=0.037 and p=0.019, respectively) and morning BMAL1 (p=0.016). No differences were observed between morning and evening protein levels in both groups. Evening HIF-1beta corraleted with evening CLOCK and morning BMAL1 (R=0.511, p=0.21 and R=0.594, p=0.006, respectively), while morning HIF-1 with evening BMAL1 (R=474, p=0.35). Furthermore, evening and morning HIF-1 correlated with evening BMAL1 (R=564, p=0.010 and R=0.689, p=0.001, respectively). Additionally, morning CLOCK and BMAL1 correlated with AHI (R=0.510, p=0.022 and R=0.560, p=0.010, respectively) and desaturation index (R=0.487, p=0.209 and R=0.570, p=0.009, respectively). Conclusion There is significant correlation between both subunits of HIF-1 protein and circadian clock proteins: CLOCK and BMAL1, which further correlate with increased disease severity. This suggests OSA patients are in risk of circadian clock disruption due to present hypoxia. Support The study was financed by Polish National Centre Grant no. 2018/31/N/NZ5/03931. </jats:sec

P060 Hypoxia-induced overexpression of Rev-Erb-alpha and NPAS2 proteins in obstructive sleep apnea patients - possible mechanism of DM2 development

Abstract Circadian clocks are endogenous coordinators of 24-hour behavioral and molecular rhythms, which disruption may be caused by obstructive sleep apnea (OSA). It is composed of a set of genes, function as activators (CLOCK, BMAL) or repressors (PER, CRY). Neuronal PAS Domain Protein 2 (NPAS2) can substitute CLOCK in its function. Orphan nuclear receptor (Rev-Erb-α) is another protein supporting the CLOCK-BMAL1 complex, forming the loop which helps to regulate their expression. There are studies suggesting the significant influence of circadian disruption mediated via NPAS2 and Rev-Erb-α on DM2 development. The aim of the study was to determine the role of NPAS2 and Rev-Erb-α in DM2 for OSA patients. All participants underwent polysomnography (PSG) examination. Based on apnea-hypopnea index accompanied by clinical data the recruited individuals (n=40) were assigned to one from 3 groups: OSA (severe OSA, no DM2; n=17), DM2 (severe OSA + DM2; n=7) and control group (no OSA, no DM2; n=16). Serum protein levels of Rev-Erb-α and NPAS2 were assessed with ELISA immunoassay. Analysis between the groups revealed the statistically significant difference only in NPAS2 protein level (p=0.037). Further post-hoc analysis revealed significant differences between OSA and the control group (p=0.017). Moreover, a statistically significant correlation between AHI and NPAS2 serum protein level was observed (r=-0.478, p=0.002). NPAS2 protein levels are associated with a number of apneas and hypopneas during the REM phase of sleep and might have a significant role in the development of OSA complications. However, further studies are needed to understand its role.</jats:p