Highlights d Postpartum liver circulates NAD metabolites to increase mammary NAD + and NADP + >20-fold d NR supplementation superinduces prolactin, mammary biosynthetic programs, and lactation d Weanlings of NR-fed mothers are hypoglycemia resistant and advanced in motor learning d Adult offspring of NR-fed mothers retain striking physical and behavioral advantages

Current methods for screening and detecting delirium are not practical in clinical settings. We previously showed that a simplified EEG with bispectral electroencephalography (BSEEG) algorithm can detect delirium in elderly inpatients. In this study, we performed a post-hoc BSEEG data analysis using larger sample size and performed topological data analysis to improve the BSEEG method. Data from 274 subjects included in the previous study were analyzed as a 1st cohort. Subjects were enrolled at the University of Iowa Hospitals and Clinics (UIHC) between January 30, 2016, and October 30, 2017. A second cohort with 265 subjects was recruited between January 16, 2019, and August 19, 2019. The BSEEG score was calculated as a power ratio between low frequency to high frequency using our newly developed algorithm. Additionally, Topological data analysis (TDA) score was calculated by applying TDA to our EEG data. The BSEEG score and TDA score were compared between those patients with delirium and without delirium. Among the 274 subjects from the first cohort, 102 were categorized as delirious. Among the 206 subjects from the second cohort, 42 were categorized as delirious. The areas under the curve (AUCs) based on BSEEG score were 0.72 (1st cohort, Fp1-A1), 0.76 (1st cohort, Fp2-A2), and 0.67 (2nd cohort). AUCs from TDA were much higher at 0.82 (1st cohort, Fp1-A1), 0.84 (1st cohort, Fp2-A2), and 0.78 (2nd cohort). When sensitivity was set to be 0.80, the TDA drastically improved specificity to 0.66 (1st cohort, Fp1-A1), 0.72 (1st cohort, Fp2-A2), and 0.62 (2nd cohort), compared to 0.48 (1st cohort, Fp1-A1), 0.54 (1st cohort, Fp2-A2), and 0.46 (2nd cohort) with BSEEG. BSEEG has the potential to detect delirium, and TDA is helpful to improve the performance.

Complications of delirium and dementia increase mortality; however, it is difficult to diagnose delirium accurately, especially among dementia patients. The bispectral electroencephalography (BSEEG) score can detect delirium and predict mortality in elderly patients. We aimed to develop an efficient and reliable BSEEG device for high-throughput screening. We also hypothesized that BSEEG score can predict mortality among dementia patients. A prospective cohort study was conducted between January 2016 to December 2018 to measure BSEEG from elderly patients and correlate with outcomes. A total of 502 elderly (55 years old or older) patients with and without dementia were enrolled. For a replication of the utility of BSEEG, mortalities between BSEEG-positive and BSEEG-negative group were compared. In addition, patients with and without dementia status was added to examine the utility of BSEEG among dementia patients. The mortality within 180 days in the BSEEG-positive group was higher than that of the BSEEG-negative group in both the replication and the total cohorts. Mortality of those in the BSEEG-positive group showed a dose-dependent increase in both cohorts. When the dementia patients showed BSEEG positive, their mortality was significantly higher than those with dementia but who were BSEEG-negative. Mortality within 30 days in the BSEEG-positive group was significantly higher than that of the BSEEG-negative group. The utility of the BSEEG to predict mortality among large sample of 502 elderly patients was shown. The BSEEG score can predict mortality among elderly patients in general, and even among dementia patients, as soon as 30 days.

Research activities with infectious severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) are currently permitted only under biosafety level 3 (BSL3) containment. Here, we report the development of a single-cycle infectious SARS-CoV-2 virus replicon particle (VRP) system with a luciferase and green fluorescent protein (GFP) dual reporter that can be safely handled in BSL2 laboratories to study SARS-CoV-2 biology. The Spike (S) gene of SARS-CoV-2 encodes for the envelope glycoprotein, which is essential for mediating infection of new host cells. Through deletion and replacement of this essential S gene with a luciferase and GFP dual reporter, we have generated a conditional SARS-CoV-2 mutant (ΔS-VRP) that produces infectious particles only in cells expressing a viral envelope glycoprotein of choice. Interestingly, we observed more efficient production of infectious particles in cells expressing vesicular stomatitis virus (VSV) glycoprotein G (ΔS-VRP(G)) as compared to cells expressing other viral glycoproteins including S. We confirmed that infection from ΔS-VRP(G) is limited to a single round and can be neutralized by anti-VSV serum. In our studies with ΔS-VRP(G), we observed robust expression of both luciferase and GFP reporters in various human and murine cell types, demonstrating that a broad variety of cells can support intracellular replication of SARS-CoV-2. In addition, treatment of ΔS-VRP(G) infected cells with anti-CoV drugs remdesivir (nucleoside analog) or GC376 (CoV 3CL protease inhibitor) resulted in a robust decrease in both luciferase and GFP expression in a drug-dose and cell-type dependent manner. Taken together, we have developed a single-cycle infectious SARS-CoV-2 VRP system that serves as a versatile platform to study SARS-CoV-2 intracellular biology and to perform high throughput screening of antiviral drugs under BSL2 containment. Importance Due to the highly contagious nature of SARS-CoV-2 and the lack of immunity in the human population, research on SARS-CoV-2 has been restricted to biosafety level 3 laboratories. This has greatly limited participation of the broader scientific community in SARS-CoV-2 research and thus has hindered the development of vaccines and antiviral drugs. By deleting the essential Spike gene in the viral genome, we have developed a conditional mutant of SARS-CoV-2 with luciferase and fluorescent reporters, which can be safely used under biosafety level 2 conditions. Our single-cycle infectious SARS-CoV-2 virus replicon system can serve as a versatile platform to study SARS-CoV-2 intracellular biology and to perform high throughput screening of antiviral drugs under BSL2 containment.

BACKGROUND/OBJECTIVES: Detecting delirium is important to identify patients with a high risk of poor outcomes. Although many different kinds of screening instruments for delirium exist, there is no solid consensus about which methods are the most effective. In addition, it is important to find the most useful tools in predicting outcomes such as mortality. DESIGN: Retrospective cohort study.