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Glutamatergic neurons in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors by regulating breathing in response to tissue CO2/H+. The RTN and greater parafacial region may also function as a chemosensing network composed of CO2/H+-sensitive excitatory and inhibitory synaptic interactions. In the context of disease, we showed that loss of inhibitory neural activity in a mouse model of Dravet syndrome disinhibited RTN chemoreceptors and destabilized breathing (Kuo et al., 2019). Despite this, contributions of parafacial inhibitory neurons to control of breathing are unknown, and synaptic properties of RTN neurons have not been characterized. Here, we show the parafacial region contains a limited diversity of inhibitory neurons including somatostatin (Sst)-, parvalbumin (Pvalb)-, and cholecystokinin (Cck)-expressing neurons. Of these, Sst-expressing interneurons appear uniquely inhibited by CO2/H+. We also show RTN chemoreceptors receive inhibitory input that is withdrawn in a CO2/H+-dependent manner, and chemogenetic suppression of Sst+ parafacial neurons, but not Pvalb+ or Cck+ neurons, increases baseline breathing. These results suggest Sst-expressing parafacial neurons contribute to RTN chemoreception and respiratory activity.

Patients with sleep-disordered breathing (SDB) have cyclic variation of heart rate (CVHR) in response to respiratory events. However, limited data are available regarding the utility of CVHR as a screening tool for SDB in mixed heart failure (HF) and non-HF patients.

We enrolled consecutive patients with and without HF who underwent full polysomnographies with simultaneous Holter electrocardiogram monitoring. We determined the temporal position of the individual dips comprising the CVHR score using time-domain methods.

The data of 101 patients, including 70 with and 31 without HF, were analyzed. The CVHR score was significantly correlated with the apnea-hypopnea index (AHI) (r = 0.667, P < 0.001) and limits of agreement between the AHI and CVHR score were -21.8 to 35.2. The receiver operating characteristic analysis demonstrated that the CVHR score (best cut-off of 23.5 events/h) identified severe SDB with a sensitivity of 83.3%, specificity of 79.5%, and the area under the curve of 0.856. In addition, there was no interaction between the presence or absence of HF and the AHI-CVHR score relationship (P = 0.323).

The CVHR score, determined by Holter electrocardiogram monitoring, is a useful tool for evaluating SDB even in mixed HF and non-HF patients.

The CVHR score, determined by Holter electrocardiogram monitoring, is a useful tool for evaluating SDB even in mixed HF and non-HF patients.

Obstructive sleep apnea (OSA) is a common disorder characterized by multiple episodes of airflow limitations and intermittent hypoxia. Pregnancy is a risk factor for developing OSA and OSA is associated with multiple adverse pregnancy outcomes and maternal morbidities, even beyond the gestational period. Despite the high prevalence of OSA and its impact on perinatal outcomes, there are no standard methods and optimal timing to screen for this disorder. Consequently, OSA is currently underdiagnosed in pregnancy. We present a case of severe OSA in pregnancy that developed in the third trimester of pregnancy after a negative study in early pregnancy. Our report emphasizes how lack of standardized screening and diagnostic methods in pregnancy can misdiagnose OSA, even in severe cases, and highlights the need for further research in this area.

Obstructive sleep apnea (OSA) is a common disorder characterized by multiple episodes of airflow limitations and intermittent hypoxia. Pregnancy is a risk factor for developing OSA and OSA is associated with multiple adverse pregnancy outcomes and maternal morbidities, even beyond the gestational period. Despite the high prevalence of OSA and its impact on perinatal outcomes, there are no standard methods and optimal timing to screen for this disorder. Consequently, OSA is currently underdiagnosed in pregnancy. We present a case of severe OSA in pregnancy that developed in the third trimester of pregnancy after a negative study in early pregnancy. Our report emphasizes how lack of standardized screening and diagnostic methods in pregnancy can misdiagnose OSA, even in severe cases, and highlights the need for further research in this area.

Research evaluating the influence of rapid eye movement suppressing antidepressants (REMS-AD) on multiple sleep latency test (MSLT) results and the value of performing actigraphy prior to this test in children and adolescents is lacking. We examined the impact of REMS-AD and actigraphy parameters on mean sleep latency (MSL) and sleep-onset REM episodes (SOREMs) on MSLT in a pediatric clinical sample.

This was a retrospective chart review at a quarternary referral center. We identified 164 MSLTs conducted in patients aged less than 18 years between 2014-2017. Correlations between REMS-AD, self-reported sleep duration, actigraphy parameters and each of the outcomes (MSL and SOREMs) were examined. 6-OHDA Regression analyses accounting for clinical characteristics were performed.

Mean age of the sample was 11.9±4.19 years, 62% were female, 28 (17%) were on REMS-AD (48% of whom were able to discontinue these medications prior to MSLT) and mean pediatric daytime sleepiness score was 21.7±6.1. MSL was 11.27±5.77 min and mean number of SOREMs 0.55±1.04. Patients on a REMS-AD at initial assessment had fewer SOREMs compared to those not taking these medications (0.17±0.19 versus 0.62±0.09; p=0.04); no difference was noted in MSL (10.36±1.10 versus 11.47±0.50; p=0.36). Increased time in bed on actigraphy (TIBa) correlated with a longer MSL and fewer SOREMs (r=0.23; p=0.04 and r=0.316; p=0.004 respectively). Following regression analyses, use of REMS-AD continued to remain associated with fewer SOREMs; greater TIBa, but not self-reported sleep duration, was associated with a longer MSL (all p<0.05).

Clinicians should account for the use of REMS-AD and utilize actigraphy to determine time in bed while interpreting the results of a pediatric MSLT.

Clinicians should account for the use of REMS-AD and utilize actigraphy to determine time in bed while interpreting the results of a pediatric MSLT.

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