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.

Excessive Inorganic Phosphate Burden Perturbed Intracellular Signaling: Quantitative Proteomics and Phosphoproteomics Analyses.

Inorganic phosphate (Pi) is an essential nutrient for the human body which exerts adverse health effects in excess and deficit. High Pi-mediated cytotoxicity has been shown to induce systemic organ damage, though the underlying molecular mechanisms are poorly understood. In this study, we employed proteomics and phosphoproteomics to analyze Pi-mediated changes in protein abundance and phosphorylation. Bioinformatic analyses and literature review revealed that the altered proteins and phosphorylation were enriched in signaling pathways and diverse biological processes. Western blot analysis confirms the extensive change in protein level and phosphorylation in key effectors that modulate pre-mRNA alternative splicing. Global proteome and phospho-profiling provide a bird-eye view of excessive Pi-rewired cell signaling networks, which deepens our understanding of the molecular mechanisms of phosphate toxicity.

Glycogen Synthase Kinase-3 Inhibition Sensitizes Pancreatic Cancer Cells to Chemotherapy by Abrogating the TopBP1/ATR-Mediated DNA Damage Response.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a predominantly fatal common malignancy with inadequate treatment options. Glycogen synthase kinase 3ß (GSK-3ß) is an emerging target in human malignancies including PDAC.Experimental Design: Pancreatic cancer cell lines and patient-derived xenografts were treated with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. Activation of the DNA damage response pathway and S-phase arrest induced by gemcitabine were assessed in pancreatic tumor cells with pharmacologic inhibition or siRNA depletion of GSK-3 kinases by immunoblotting, flow cytometry, and immunofluorescence. RESULTS: 9-ING-41 treatment significantly increased pancreatic tumor cell killing when combined with chemotherapy. Inhibition of GSK-3 by 9-ING-41 prevented gemcitabine-induced S-phase arrest suggesting an impact on the ATR-mediated DNA damage response. Both 9-ING-41 and siRNA depletion of GSK-3 kinases impaired the activation of ATR leading to the phosphorylation and activation of Chk1. Mechanistically, depletion or knockdown of GSK-3 kinases resulted in the degradation of the ATR-interacting protein TopBP1, thus limiting the activation of ATR in response to single-strand DNA damage. CONCLUSIONS: These data identify a previously unknown role for GSK-3 kinases in the regulation of the TopBP1/ATR/Chk1 DNA damage response pathway. The data also support the inclusion of patients with PDAC in clinical studies of 9-ING-41 alone and in combination with gemcitabine.