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Background: K+ channel inhibition has been identified in animal models as a potential target to increase pharyngeal dilator muscle activity and treat obstructive sleep apnea (OSA). However, these findings have not yet been translated to humans.Research Question: Does a novel, potent, TASK 1/3 channel antagonist, BAY2586116, improve pharyngeal collapsibility in pigs and humans and secondarily, what is the optimal dose and mode of topical application?Study Design and Methods: Pre-clinical study: Pharyngeal muscle activity and upper-airway collapsibility via transient negative pressure application was quantified in 13 anesthetized pigs during placebo, 0.3, 3 and 30μg nasal drops of BAY2586116.Clinical Study: 12 people with OSA instrumented with polysomnography equipment, an epiglottic pressure catheter, pneumotachograph and nasal mask to monitor sleep and breathing performed up to four detailed upper airway sleep physiology studies. Participants received BAY2586116 or placebo nasal spray (160μg) prior to sleep via a double-blind, randomized, crossover design. Most participants also returned for three additional overnight visits: 1) nasal drops (160μg), 2) half dose nasal spray (80μg), and 3) direct endoscopic application (160μg). The upper-airway critical closing pressure (Pcrit) during sleep was quantified at each visit.Results: There were consistent and sustained improvements in pharyngeal collapsibility to negative pressure with 3 and 30μg of BAY2586116 versus placebo in pigs. Similarly, BAY2586116 improved pharyngeal collapsibility by an average of ∼2cmH2O versus placebo regardless of topical application mode and dose (mixed model p<0.008) in participants with OSA.Interpretation: Acute topical application of BAY2586116 improves upper-airway collapsibility in anesthetized pigs and sleeping humans with OSA. These novel physiology findings highlight the therapeutic potential to target K+ channel mechanisms to treat OSA.Clinical Trial Registration: NCT04236440. [ABSTRACT FROM AUTHOR]

A novel one transistor and one diode (1T-1D) dynamic random access memory cell for embedded applications is proposed. This memory cell consists of a floating-gate (FG) MOSFET and a gated diode. The anode of the diode is connected to the FG, so that the threshold voltage of the FG MOSFET can be modulated by the current through the diode. In this paper, basic device operations, speed, retention, and disturb performance are investigated using Silvaco technology computer-aided design simulation tools. The process compatibility is also investigated by integrating the memory array and specific sense amplifier. [ABSTRACT FROM PUBLISHER]