High phosphate actively induces cytotoxicity by rewiring pro-survival and pro-apoptotic signaling networks in HEK293 and HeLa cells.

Inorganic phosphate (Pi) is an essential nutrient for human health. Due to the changes in our dietary pattern, dietary Pi overload engenders systemic phosphotoxicity, including excessive Pi-related vascular calcification and chronic tissue injury. The molecular mechanisms of the seemingly distinct phenotypes remain elusive. In this study, we investigated Pi-mediated cellular response in HEK293 and HeLa cells. We found that abnormally high Pi directly mediates diverse cellular toxicity in a dose-dependent manner. Up to 10 mM extracellular Pi promotes cell proliferation by activating AKT signaling cascades and augmenting cell cycle progression. By introducing additional Pi, higher than the concentration of 40 mM, we observed significant cell damage caused by the interwoven Pi-related biological processes. Elevated Pi activates mitogen-activated protein kinase (MAPK) signaling, encompassing extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and Jun amino-terminal kinase (JNK), which consequently potentiates Pi triggered lethal epithelial-mesenchymal transition (EMT). Synergistically, high Pi-caused endoplasmic reticulum (ER) stress also contributes to apparent apoptosis. To counteract, Pi-activated AKT signaling promotes cell survival by activating the mammalian target of rapamycin (mTOR) signaling and blocking ER stress. Pharmacologically or genetically abrogating Pi transport, the impact of high Pi-induced cytotoxicity could be reduced. Taken together, abnormally high extracellular Pi results in a broad spectrum of toxicity by rewiring complicated signaling networks that control cell growth, cell death, and homeostasis.

Impact of COVID-19 pandemic on emergency psychiatry-Millcreek community hospital, Erie, PA.

OBJECTIVE: Evidence suggested that traumatic events, including pandemics, can be associated with psychiatric symptoms like increased anxiety and depression. However, there were many unknowns concerning the emergent global coronavirus-19 (COVID-19), including its impact on psychiatric health within the United States. Our study aimed to track trends of mental health problems in individuals who presented with psychiatric complaints in an emergent setting. METHODS: A total of 1776 patients and 1610 patients presented to Emergency Department (ED) with psychiatric complaints between January 1 - July 9 of the years of 2019 and 2020, respectively, in Millcreek Community Hospital (MCH) Erie, PA. This study was an electronic medical record review (EMR), therefore the data were collected exclusively from EMR over the two-year span. ED prevalence was calculated as the number of total psychiatric MCH ED cases divided by the total number of all MCH ED patients, and prevalence ratio (PR) between 2019 and 2020 was used to reflect change of overall ED psychiatric prevalence. RESULTS: Clinical notes revealed increased ED psychiatric chief complaint prevalence, as indicated by a PR greater than one, in multiple categories in comparison to before the COVID-19 outbreak. Concerning primary psychiatric disorders, there was increased ED prevalence in chief complaint of total mood disorders (PR = 1.21) with major depressive disorder (PR = 1.23) and bipolar disorder (PR = 1.47), neurodevelopment disorders (PR = 1.25) with attention deficit hyperactivity disorder (ADHD) (PR = 1.19) and intellectual disability (PR = 1.52), trauma- and stressor-related disorders (PR = 1.56) with post-traumatic stress disorder (PTSD) (PR = 1.39) and adjustment disorder (PR = 1.73), substance abuse and addiction disorders (PR = 1.29), and personality disorders (PR = 1.56). CONCLUSIONS: The pandemic outbreak dramatically impacted mental health in an ER setting. Further research on mental health disparities in conjunction with the COVID-19 pandemic is critical to help predict and address risk for chronic symptoms and sequela to help anticipate and improve psychiatric patient care and well-being during potential future pandemics.