The human endometrial epithelium is pivotal to menstrual cycle progression, implantation and early pregnancy. Endometrial function is directly regulated by local factors that include pH, oxygen tension and ion concentrations to generate an environment conducive to fertilization. A superfamily of potassium channels characterized by two-pore domains (K2P) and encoded by KCNK genes is implicated in the control of the cell resting membrane potential through the generation of leak currents and modulation by various physicochemical stimuli. The aims of the study were to determine the expression and function of K2P channel subtypes in proliferative and secretory phase endometrium obtained from normo-ovulatory women and in an endometrial cancer cell line. Using immunochemical methods, real-time qRT-PCR proliferation assays and electrophysiology. Our results demonstrate mRNA for several K2P channel subtypes in human endometrium with molecular expression of TREK-1 shown to be higher in proliferative than secretory phase endometrium (P < 0.001). The K2P channel blockers methanandamide, lidocaine, zinc and curcumin had antiproliferative effects (P < 0.01) in an endometrial epithelial cancer cell line indicating a role for TASK and TREK-1 channels in proliferation. Tetraethylammonium- and 4-aminopyridine-insensitive outwards currents were inhibited at all voltages by reducing extracellular pH from 7.4 to 6.6. Higher expression of TREK-1 expression in proliferative phase endometrium may, in part, underlie linked to increased cell division. The effects of pH and a lack of effect of non-specific channel blockers of voltage-gated potassium channels imply a role for K2P channels in the regulation of human endometrial function.
The urgency to understand the long-term neuropsychiatric sequala of COVID-19, a part of the Post-Acute COVID-19 Syndrome (PACS), is expanding as millions of infected individuals experience new unexplained symptoms related to mood, anxiety, insomnia, headache, pain, and more. Much research on PACS involves cross sectional surveys which limits ability to understand the dynamic trajectory of this emerging phenomenon. In this secondary analysis, we analyzed data from a 4-week observational digital phenotyping study using the mindLAMP app for 695 college students with elevated stress who specified if they were exposed to COVID-19. Students also completed a biweekly survey of clinical assessments to obtain active data. Additionally, passive data streams like GPS, accelerometer, and screen state were extracted from phone sensors and through features the group built. Three hundred and eighty-second number participants successfully specified their COVID-19 exposure and completed the biweekly survey. From active smartphone data, we found significantly higher scores for the Prodromal Questionnaire (PQ) and the Pittsburgh Sleep Quality Index (PSQI) for students reporting exposure to COVID-19 compared to those who were not (ps < 0.05). Additionally, we found significantly decreased sleep duration as captured from the smartphone via passive data for the COVID-19 exposed group (p < 0.05). No significant differences were detected for other surveys or passive sensors. Smartphones can capture both self-reported symptoms and behavioral changes related to PACS. Our results around changes in sleep highlight how digital phenotyping methods can be used in a scalable and accessible manner toward better capturing the evolving phenomena of PACS. The present study further provides a foundation for future research to implement improving digital phenotyping methods.
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