Olfactory Malfunction in People Have been infected with 2019 Novel Coronavirus.
  © 2020, White et al.The TMEM175 family constitutes recently discovered K+ channels that are important for autophagosome turnover and lysosomal pH regulation and are associated with the early onset of Parkinson Disease. TMEM175 channels lack a P-loop selectivity filter, a hallmark of all known K+ channels, raising the question how selectivity is achieved. Here, we report the X-ray structure of a closed bacterial TMEM175 channel in complex with a nanobody fusion-protein disclosing bound K+ ions. Our analysis revealed that a highly conserved layer of threonine residues in the pore conveys a basal K+ selectivity. An additional layer comprising two serines in human TMEM175 increases selectivity further and renders this channel sensitive to 4-aminopyridine and Zn2+. Our findings suggest that large hydrophobic side chains occlude the pore, forming a physical gate, and that channel opening by iris-like motions simultaneously relocates the gate and exposes the otherwise concealed selectivity filter to the pore lumen. © 2020, Brunner et al.Axons span extreme distances and are subjected to significant stretch deformations during limb movements or sudden head movements, especially during impacts. Yet, axon biomechanics, and its relation to the ultrastructure that allows axons to withstand mechanical stress, is poorly understood. Using a custom developed force apparatus, we demonstrate that chick dorsal root ganglion axons exhibit a tension buffering or strain-softening response, where its steady state elastic modulus decreases with increasing strain. We then explore the contributions from the various cytoskeletal components of the axon to show that the recently discovered membrane-associated actin-spectrin scaffold plays a prominent mechanical role. Finally, using a theoretical model, we argue that the actin-spectrin skeleton acts as an axonal tension buffer by reversibly unfolding repeat domains of the spectrin tetramers to release excess mechanical stress.  https://www.selleckchem.com/products/OSI-906.html  Our results revise the current view point that microtubules and their associated proteins are the only significant load-bearing elements in axons. © 2020, Dubey et al.STUDY OBJECTIVES The multiple sleep latency test (MSLT) has limitations when evaluating disorders of hypersomnolence with unknown etiology. Alternative measures of hypersomnolence may objectively identify pathology in patients with complaints of daytime sleepiness that may not be captured by the MSLT alone. This study evaluated the impact of a multimodal hypersomnolence assessment relative to MSLT in patients with unexplained hypersomnolence.  https://www.selleckchem.com/products/OSI-906.html  METHODS Seventy-five patients with unexplained hypersomnolence were included in the analyzed sample. Polysomnography was performed without prescribed wake time, and the psychomotor vigilance task (PVT) and pupillographic sleepiness test (PST) were completed between MSLT nap opportunities. Presence or absence of hypersomnolence for each assessment was defined using a priori cutpoints. Proportions of patients identified as hypersomnolent using the multimodal assessment relative to MSLT alone were evaluated, as well as the sensitivity and specificity of ancillary hypersomnolence measures relative to MSLT as a gold standard. RESULTS The multimodal assessment more than doubled the proportion of patients identified as having objective deficits relative to MSLT≤8 minutes alone. The combination of excessive sleep duration, lapses on the PVT, and impairments on PST also had perfect sensitivity in identifying all patients identified as sleepy by the MSLT across three different MSLT cutpoints (5, 8, and 10 minutes). CONCLUSIONS These data demonstrate the insufficiency of the MSLT as a singular tool to identify objective pathology in persons with unexplained hypersomnolence. Further efforts to refine and standardize multimodal assessments will likely improve diagnostic acumen and research into the causes of these disorders. © 2020 American Academy of Sleep Medicine.STUDY OBJECTIVES People with obstructive sleep apnea (OSA) remain undiagnosed owing to lack of easy and comfortable screening tools. Through this study, we aimed to compare the diagnostic accuracy of chest wall motion and cyclic variation of heart rate (CVHR) in detecting OSA by using a single-lead electrocardiogram (ECG) patch with a 3-axis accelerometer. METHODS In total, 119 snoring patients simultaneously underwent polysomnography (PSG) with a single-lead ECG patch. Signals of chest wall motion and CVHR from the single-lead ECG patch were collected. The chest effort index (CEI) was calculated using the chest wall motion recorded by a 3-axis accelerometer in the device. The ability of CEI and CVHR indices in diagnosing moderate-to-severe OSA (apnea hypopnea index ≥ 15) was compared using the area under the curve (AUC) by using the DeLong test. RESULTS CVHR detected moderate-to-severe OSA with 52.9% sensitivity and 94.1% specificity (AUC 0.76, 95% confidence interval [CI] 0.67-0.84, optimal cutoff 21.2 events/h). By contrast, CEI identified moderate-to-severe OSA with 80% sensitivity and 79.4% specificity (AUC 0.87, 95% CI 0.80-0.94, optimal cutoff 7.1 events/h). CEI significantly outperformed CVHR with regard to the discrimination ability for moderate-to-severe OSA (delta AUC 0.11, 95% CI 0.009-0.21, P = 0.032). For determining severe OSA, the performance of discrimination ability was greater (AUC = 0.90, 95% CI 0.85-0.95) when combining these two signals. CONCLUSIONS Both CEI and CVHR recorded from a patch-type device with ECG and a 3-axis accelerometer can be used to detect moderate-to-severe OSA. Thus, incorporation of CEI is helpful in the detection of sleep apnea by using a single-lead ECG with a 3-axis accelerometer. © 2020 American Academy of Sleep Medicine.STUDY OBJECTIVES The variable efficacy of mandibular advancement device (MAD) treatment necessitates both accessible and accurate methods for patient selection. The role of awake nasopharyngoscopy for this purpose, however, remains dubious. We introduced an assessment method based on anatomical upper airway features during tidal breathing for nasopharyngoscopy. The current study aimed to relate these features to MAD treatment outcome. METHODS One hundred patients diagnosed with obstructive sleep apnea were prospectively recruited for MAD treatment in a fixed 75% degree of maximal protrusion. Nasopharyngoscopic observations during Müller's maneuver and tidal breathing were recorded both with and without MAD. Treatment outcome, confirmed by three-month follow-up polysomnography with MAD, was classified as (1) apnea-hypopnea index (AHI) reduction ≥50%, (2) treatment AHI less then 5 events/h, and (3) ≥10% increase in AHI compared to baseline (treatment deterioration). RESULTS A complete dataset was obtained in 65 patients.