Exploring the dynamics of snoring in relation to sleep stages: Implications for gender differences, sleep position, and upper airway collapsibility.

OBJECTIVE: The purpose of this study was to determine the sleep stage during which isolated snoring occurs in children and adults, and to analyze changes after treatment of obstructive sleep apnea (OSA). METHODS: This retrospective study examined duration of snoring time and respiratory events during each sleep stage in adults and children who underwent polysomnography, had an apnea-hypopnea index (AHI) < 15/h and had snoring time ≥ 10% of total sleep time. Changes in duration of snoring time were also examined in adult patients after treatment with an oral appliance (OA). RESULTS: Snoring time was shown to be predominant during N3 and N2 sleep and less dominant during REM sleep in both children (n = 47) and adults (n = 93). These results were seen even in children with REM dependency. The percentage of snoring time during N3 sleep was more pronounced in women than in men among young adult patients aged < 40 years but was not significantly different between men and women overall. There were no significant differences in the percentage of snoring time in each sleep stage between young women with mild OSA and non-OSA. In children, there were no significant differences between boys and girls in the percentage of snoring time in any sleep stage. The percentage of snoring time during N3 was significantly higher sleep in the non-supine position than in the supine position in children, whereas no significant differences were noted between the supine and non-supine positions in any sleep stage in adults. OA treatment for adult patients (n = 20) significantly increased the percentage of snoring time during N3 sleep, although it significantly decreased AHI, total snoring time, and snoring time during N1 sleep and REM sleep. CONCLUSIONS: Snoring presented exclusively during the N3 sleep stage, especially in young women with mild OSA, and in children with OSA, especially in the non-supine position. Snoring time during N3 sleep increased during OA treatment for OSA.

A novel PET probe to selectively image heat shock protein 90α/ß isoforms in the brain.

BACKGROUND: Heat shock proteins (HSPs) are present throughout the brain. They function as molecular chaperones, meaning they help with the folding and unfolding of large protein complexes. These chaperones are vital in the development of neuropathological conditions such as Alzheimer's disease and Lewy body disease, with HSP90, a specific subtype of HSP, playing a key role. Many studies have shown that drugs that inhibit HSP90 activity have beneficial effects in the neurodegenerative diseases. Therefore, HSP90 PET imaging ligand can be used effectively to study HSP90 in neurodegenerative diseases. Among four HSP90 isoforms, two cytosolic isoforms (HSP90α and HSP90ß) thought to be involved in the structural homeostasis of the proteins related to the neurodegenerative diseases. Currently, no useful PET imaging ligands selectively targeting the two cytosolic isoforms of HSP90 have been available yet. RESULTS: In this study, we developed a novel positron emission tomography (PET) imaging ligand, [11C]BIIB021, by 11C-radiolabeling (a positron emitter with a half-life of 20.4 min) 6-Chloro-9-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-9H-purin-2-amine (BIIB021), an inhibitor with a high affinity for and selectivity to HSP90α and HSP90ß. [11C]BIIB021 was synthesized with a high yield, molar activity and radiochemical purity. [11C]BIIB021 showed a high binding affinity for rat brain homogenate as well as human recombinant HSP90α and HSP90ß proteins. Radioactivity was well detected in the rat brain (SUV 1.4). It showed clear specific binding in PET imaging of healthy rats and autoradiography of healthy rat and human brain sections. Radiometabolite was detected in the brain, however, total distribution volume was well quantified using dual-input graphical model. Inhibition of p-glycoprotein increased brain radioactivity concentrations. However, total distribution volume values with and without p-glycoprotein inhibition were nearly the same. CONCLUSIONS: We have developed a new PET imaging agent, [11C]BIIB021, specifically targeting HSP90α/ß. We have been successful in synthesizing [11C]BIIB021 and in vitro and in vivo imaging HSP90α/ß. However, the quantification of HSP90α/ß is complicated by the presence of radiometabolites in the brain and the potential to be a substrate for p-glycoprotein. Further efforts are needed to develop radioligand suitable for imaging of HSP90α/ß.