Heterologous Production of the D-Cycloserine Intermediate O-acetyl-L-serine in Human Lung Cancer Cells

According to the World Health Organization, Tuberculosis (TB) is the second leading cause of death by a single infectious disease behind COVID-19. Despite a century of effort, the current TB vaccine does not effectively prevent pulmonary TB, promote herd immunity, or prevent transmission. Therefore, we seek to develop a genetic prophylaxis for TB. We have determined D-cycloserine to be the optimal target for this approach due to its relatively short six-enzyme biosynthetic pathway. D-CS is a second-line antibiotic for TB that inhibits bacterial cell wall synthesis. The first committed step towards D-CS synthesis is catalyzed by the L-serine-O-acetyltransferase (DcsE) which converts L-serine and acetyl-CoA to O-acetyl-L-serine (L-OAS). To test if the D-CS pathway could be an effective prophylaxis for TB in human cells, we endeavored to express DcsE in human cells and test its functionality. We overexpressed DcsE tagged with FLAG and GFP in A549 lung cancer cells as determined using fluorescence microscopy. We observed that purified DcsE catalyzed the synthesis of L-OAS as observed by HPLC-MS. Therefore, DcsE synthesized in human cells is a functional enzyme capable of converting L-serine and acetyl-CoA to L-OAS demonstrating the first step towards DCS production in human cells.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Influenza-Associated Hospitalization Rates and Proportion of Hospitalizations with Influenza and SARS-CoV-2 Coinfection, FluSurv-NET, October 1, 2021-April 23, 2022

Background. Influenza-associated hospitalization rates were low during the 2020-21 season. We describe influenza-associated hospitalization rates and prevalence of influenza and SARS-CoV-2 coinfection among patients hospitalized with influenza during 2021-22. Methods. We used data from the Influenza Hospitalization Surveillance Network (FluSurv-NET), a population-based surveillance system for laboratoryconfirmed influenza-associated hospitalizations active from October-April of each year. We calculated cumulative and weekly hospitalization rates per 100,000 population and compared preliminary rates during 2021-22 with prior season rates (2010-11 through 2020-21). We determined the proportion of influenza-associated hospitalizations with SARS-CoV-2 coinfection during 2021-22. Results. During October 1, 2021-April 23, 2022, 3,262 influenza-associated hospitalizations were reported to FluSurv-NET;the cumulative hospitalization rate of 11.1 was higher than 2011-12 and 2020-21 season rates, but lower than rates observed during all other seasons since 2010-11 (Figure 1A). After peaking in the week ending January 1, 2022 (MMWR week 52), weekly hospitalization rates declined until the week ending February 19, 2022 (MMWR week 7) when they began to rise modestly, similar to patterns observed during several prior seasons (Figure 1B). Among the 3,262 hospitalizations, 87 (2.7%) had SARS-CoV-2 coinfection;the prevalence by age group was as follows: 0-17 years 3.4%, 18-49 years 2.8%, 50-64 years 3.5%, 65-74 years 2.5%, >= 75 years 1.6%. Among the 3,262 influenza-associated hospitalizations, the prevalence of SARS-CoV-2 coinfection by month (October 2021- April 2022), respectively, was 11.4%, 2.5%, 2.6%, 8.9%, 3.4%, 0.8%, and 0.5%. Conclusion. SARS-CoV-2 coinfection was uncommon among patients hospitalized with influenza during 2021-22. Likely due to ongoing COVID-19 mitigation measures, the influenza-associated hospitalization rate during 2021-22 was lower than rates observed in most seasons in the decade preceding the COVID-19 pandemic. A late rise in weekly influenza hospitalization rates in 2021-22 might have been a result of relaxation of COVID-19 mitigation measures and/or a late season peak in influenza activity. (Figure Presented).

Extracting Economic Signals from Central Bank Speeches

Estimating the effects of monetary policy is one of the fundamental research questions in monetary economics. Many economies are facing ultra-low interest rate environments ever since the global financial crisis of 2007-9. The Covid pandemic recently reinforced this situation. In the US and Europe, interest rates are close to (or even below) zero, which limits the scope of traditional monetary policy measures for central banks. Dedicated central bank communication has hence become an increasingly important tool to steer and control market expectations these days. However, incorporating central bank language directly as features into economic models is still a very nascent research area. In particular, the content and effect of central bank speeches has been mostly neglected from monetary policy modelling so far. With our paper, we aim to provide to the research community a novel, monetary policy shock series based on central bank speeches. We use a supervised topic modeling approach that can deal with text as well as numeric covariates to estimate a monetary policy signal dispersion index along three key economic dimensions: GDP, CPI and unemployment. This "dispersion shock" series is not only more frequent than series that classically focus on policy announcement dates, it also opens up the possibility of answering new questions that have up until now been difficult to analyse. For example, do markets form different expectations when facing a "cacophony of policy voices"? Our initial findings for the US point towards the fact that more dispersed or incongruent monetary policy stance communication in the build up to Federal Open Market Committee (FOMC) meetings might be associated with stronger subsequent market surprises at FOMC policy announcement time. © 2021 Association for Computational Linguistics.

Distress Screening among Oncology Patients in the Acute Care Setting during the U.S. COVID-19 Pandemic

Background/Purpose: The ongoing COVID-19 pandemic has impacted psychosocial experiences of cancer patients due to factors such as delayed treatments, decreased medical resources and fear of treatment availability, as well as need for social distancing and reduced availability of social support during cancer treatment and inpatient hospitalizations. This program evaluation was conducted to understand how the frequency of positive inpatient distress screening (DS) scores changed during March 2020 to August 2021 in the context of the U.S. COVID-19 pandemic. Methods: The Patient Health Questionnaire-4 (PHQ-4) was used to assess distress and was administered by oncology nurses 36 h postadmission. Within institutional DS guidelines, positive scores were ≥4 on the PHQ-4 or ≥3 on anxiety or depression subscales. Results: In the 12 months prior to the U.S. COVID-19 pandemic (March 2019-February 2020), there were 1343 inpatient oncology DS, of which 137 (10.2%) were positive. In the first 12 months of the pandemic (March 2020-February 2021), there were 1309 inpatient oncology DS, of which 177 (13.5%) were positive. In months 13-18 of the pandemic (March 2021-August 2021), there were 941 inpatient oncology DS, of which 144 (15.3%) were positive. Conclusions and Implications: Inpatient oncology DS data suggested an increased frequency of distress among oncology patients hospitalized during the pandemic, rising from 10.2% of total screens in the pre-pandemic year to 13.5% during the first year of the pandemic and 15.3% in the following 6 months. Given the ongoing pandemic and particular challenges faced by oncology patients, it is important to consider both the short- and long-term potential impacts among oncology patients in acute care settings. Psychosocial Oncology programs and clinicians should maintain awareness of the multiple factors, both collective (e.g., pandemic, systemic racism/racial injustice) and personal (i.e., diagnosis/treatment, psychosocial) impacting distress in acute care settings and consider scalable, longitudinal assessment and intervention strategies to support patients.

An audit of the well-being of staff working in intellectual disability settings in Ireland during the COVID-19 pandemic

Purpose: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected millions of people worldwide. Individuals with intellectual disability are at a disproportionate risk of mortality, given the health inequalities they experience. This puts a significant burden of responsibility on staff who support these individuals. Consequently, this study aims to establish a baseline of the well-being of staff working in intellectual disability services in Ireland during the COVID-19 pandemic. Design/methodology/approach: An online survey was carried out using the Copenhagen Burnout Inventory, a brief measure of depression (Patient Health Questionnaire-9) and a brief measure of anxiety (General Anxiety Disorder-7). Findings: In total, 285 staff in the Republic of Ireland completed the survey. These staff reported moderate levels of personal and work-related burnout and mild levels of anxiety and depression. Higher mean scores were recorded across scales from staff who worked in independent living settings and from staff who supported individuals with challenging behaviour. Originality/value: This study, an audit, provides initial data on the well-being of staff working with individuals with intellectual disability in Ireland during the COVID-19 pandemic. It highlights that employers need to consider staff well-being, given the levels of personal and work-related burnout, and anxiety and depression that were found. This is particularly true for staff who work in independent living settings and with adults with challenging behaviour. Future research should focus on proactive strategies for improving staff well-being in the short term, given the current resurgence of COVID-19 in Ireland. © 2020, Emerald Publishing Limited.