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STUDY OBJECTIVES: The implementation of positive airway pressure (PAP) therapy to treat obstructive sleep apnea in children is a complex process. PAP therapy data are highly heterogeneous in pediatrics, and the clinical management cannot be generalized. We hypothesize that pediatric PAP users can be subgrouped via clustering analysis to guide tailored interventions. METHODS: PAP therapy data for 250 children with obstructive sleep apnea were retrospectively examined using unsupervised hierarchical cluster analysis based on (1) PAP tolerance (average hours on days used) and (2) consistency of PAP use (percentage of days used). Clinical features in each cluster were defined, and a tree decision analysis was generated for clinical implementation. RESULTS: We were able to subclassify all 250 children (median age = 11.5 years) into five clusters: A (13.6%), B (29.6%), C (17.6%), D (16.4%), and E (22.8%). The clusters showed significant differences in PAP use patterns (Kruskal-Wallis P value < 1e–16). The most consistent PAP use patterns were seen in clusters A, B, and C. Major differences across clusters included the prevalence of obesity, PAP setting, developmental delay, and adenotonsillectomy. We also identified important differences in mask acceptance, OSA severity, and individual responses to PAP therapy based on objective apnea-hypopnea reductions in PAP downloads. CONCLUSIONS: A simple method to subset PAP use patterns in children can be implemented by analyzing cloud-based PAP therapy data. This novel approach may contribute to optimization of PAP therapy in children of all ages based on real-world evidence at the individual level. CITATION: Weiss MR, Allen ML, Landeo-Gutierrez JS, et al. Defining the patterns of PAP adherence in pediatric obstructive sleep apnea: a clustering analysis using real world data. J Clin Sleep Med. 2021;17(5):1005–1013.

Behavioural studies widely implicate sleep in memory consolidation in the learning of a broad range of behaviours1-4. During sleep, brain regions are reactivated5,6, and specific patterns of neural activity are replayed7-10, consistent with patterns observed in prior waking behaviour. Birdsong learning is a paradigmatic model system for skill learning11-14. Song development in juvenile zebra finches is characterised by sleep-dependent circadian fluctuations in singing behaviour, with immediate post-sleep deterioration in song structure followed by recovery later in the day15. In sleeping adult birds, spontaneous bursting activity of forebrain premotor neurones in the robust nucleus of the arcopallium (RA) carries information about daytime singing16. Here we show that in juvenile zebra finches, playback during the day of an adult “tutor” song induced profound and tutor song-specific changes in bursting activity of RA neurones during the following night of sleep. The night-time neuronal changes preceded tutor song-induced changes in singing, first observed the following day. Interruption of auditory feedback greatly reduced sleep bursting and prevented the tutor song-specific neuronal remodelling. Thus, night-time neuronal activity is shaped by the interaction of the song model (sensory template) and auditory feedback, with changes in night-time activity proceeding the onset of practice associated with vocal learning. We hypothesise that night-time bursting induces adaptive changes in premotor networks during sleep as part of vocal learning. By this hypothesis, plastic changes are driven by replay of sensory information at night and evaluation of sensory feedback during the day, with the interaction between the two leading to complex circadian patterns such as are seen early in vocal development.

We describe for the first time a naturally occurring lysine modification that is converted to methyllysine by reduction with sodium borohydride. This modification is approximately 1.7 times as abundant in soluble proteins from human substantia nigra pars compacta as in proteins from other brain regions, possibly as a result of elevated oxidative stress in the nigra. Proteins from cultured PC12 cells exposed to oxidative stress conditions also contain elevated levels of this lysine modification. The abundance of the naturally occurring modification is roughly 0.08 nmoles/mg protein in either unstressed brain or PC12 cells. Modification levels remain stable in isolated proteins incubated for 2 h at 37 degrees C in pH 7 buffer. We propose that the endogenous modification is the lysine Schiff base, epsilon-N-methylenelysine, and that lysine modifications may result from a reaction with formaldehyde in vivo. Rat brain contains approximately 60 nmoles/g wet weight of formaldehyde, which probably includes both free and reversibly bound forms. Adding approximately 35 microm HCHO to PC12 cell growth medium introduces methylenelysine modifications in cell proteins and impairs cell viability. The existence of this post-translational modification suggests new mechanisms of oxidative stress that may contribute to tissue degeneration, including loss of nigral dopamine neurons during normal aging and in Parkinson's disease.

Glucocorticoid receptors (GRs) are present at a high density in the nucleus of the solitary tract (NTS), an area of the dorsal hindbrain (DHB) that is critical for blood pressure regulation. However, whether these receptors play any role in the regulation of blood pressure is unknown. We tested the hypothesis that glucocorticoids act in the DHB to increase arterial pressure using two experimental strategies. In one approach, we implanted pellets of corticosterone (Cort) or sham pellets onto the DHB over the NTS. Compared with rats with sham pellets, rats with DHB Cort pellets had an increased ( P < 0.05) mean arterial pressure (111 ± 2 vs. 104 ± 1 mmHg) and heart rate (355 ± 9 vs. 326 ± 5 beats/min) after 4 days. In the second approach, we implanted subcutaneous Cort pellets to increase the systemic Cort concentration and then subsequently implanted pellets of the GR antagonist mifepristone (Mif; previously RU-38486) or sham pellets onto the DHB. Two days of DHB Mif treatment reduced ( P < 0.05) mean arterial pressure in those rats with elevated plasma Cort levels (118 ± 2 vs. 108 ± 1 mmHg for sham vs. Mif DHB pellets). Cort and Mif pellets placed on the dura had no effects on arterial pressure or heart rate, ruling out systemic cardiovascular effects of the steroids. DHB Cort treatment had no effects on plasma Cort concentration or adrenal weight, indicating that the contents of the DHB Cort pellet did not diffuse into the systemic circulation or into the forebrain areas that regulate plasma Cort concentration in concentrations sufficient to produce physiological effects. Immunohistochemistry for the occupied GRs demonstrated that the Cort and Mif from the DHB pellets were delivered to the DHB with minimal diffusion to the ventral hindbrain or forebrain. We conclude that glucocorticoids act in the DHB to increase arterial pressure.

A suite of complex electroencephalographic patterns of sleep occurs in mammals. In sleeping zebra finches, we observed slow wave sleep (SWS), rapid eye movement (REM) sleep, an intermediate sleep (IS) stage commonly occurring in, but not limited to, transitions between other stages, and high amplitude transients reminiscent of K-complexes. SWS density decreased whereas REM density increased throughout the night, with late-night characterized by substantially more REM than SWS, and relatively long bouts of REM. Birds share many features of sleep in common with mammals, but this collective suite of characteristics had not been known in any one species outside of mammals. We hypothesize that shared, ancestral characteristics of sleep in amniotes evolved under selective pressures common to songbirds and mammals, resulting in convergent characteristics of sleep.

We describe for the first time a naturally occurring lysine modification that is converted to methyllysine by reduction with sodium borohydride. This modification is approximately 1.7 times as abundant in soluble proteins from human substantia nigra pars compacta as in proteins from other brain regions, possibly as a result of elevated oxidative stress in the nigra. Proteins from cultured PC12 cells exposed to oxidative stress conditions also contain elevated levels of this lysine modification. The abundance of the naturally occurring modification is roughly 0.08 nmoles/mg protein in either unstressed brain or PC12 cells. Modification levels remain stable in isolated proteins incubated for 2 h at 37 degrees C in pH 7 buffer. We propose that the endogenous modification is the lysine Schiff base, epsilon-N-methylenelysine, and that lysine modifications may result from a reaction with formaldehyde in vivo. Rat brain contains approximately 60 nmoles/g wet weight of formaldehyde, which probably includes both free and reversibly bound forms. Adding approximately 35 microm HCHO to PC12 cell growth medium introduces methylenelysine modifications in cell proteins and impairs cell viability. The existence of this post-translational modification suggests new mechanisms of oxidative stress that may contribute to tissue degeneration, including loss of nigral dopamine neurons during normal aging and in Parkinson's disease.

The purpose of this paper is to show that temporomandibular disorders manifest as much in children and adolescents as in adults. Objective signs, such as pain in the temporomandibular joint area to palpation or function, were found to be 40.6% on average from ages 6-18 years. Subjective signs reported by patients or their parents, such as clicking, pain to function and muscle tenderness, had an average prevalence of 38.7%. All but one researcher reported no difference between signs and symptoms as related to sex. These same articles concurred that the symptoms in children and adolescents, though less severe, were slightly higher in incidence than the adult population. Since the prevalence of signs and symptoms of temporomandibular disorders is the same in children and adolescents as in adults, more attention needs to be placed on its recognition in this age group. In addition, more research into treatment modalities and possible preventive measures in this age group is required to prevent sequelae in later years.