The ongoing impact of COVID-19 on asthma and pediatric emergency health-seeking behavior in the Bronx, an epicenter.

BACKGROUND: The Bronx has the highest prevalence of asthma in the United States (US), and was also an early COVID-19 epicenter, making it a unique study location. Worldwide reports describe significant declines in pediatric emergency department (PED) visits during COVID-19. The ongoing impact of COVID-19 on all PED presentations, including asthma, at an early epicenter has not been studied beyond the pandemic peak and into the early phases of state re-opening. OBJECTIVES: To compare PED health-seeking behaviors and clinical characteristics during the 2020 pandemic and subsequent initial New York State (NYS) phased re-opening to the same period in 2019. METHODS: Retrospective chart review of children <21 years utilizing the PED at a high-volume quaternary children's hospital in The Bronx, NY from March 15th 2020 - July 6th 2020 (pandemic cohort) and the same interval in 2019 (comparison cohort). Visits were assigned to pre-determined diagnostic categories. Demographic and clinical data were compared. RESULTS: 19,981 visits were included. Visits declined by 66% during 2020. Proportions of asthma visits (2% vs. 7%, p < 0.0001) and minor medical problems (61% vs. 67%, p < 0.0001) had significant declines in the pandemic cohort, while major medical problems (13% vs. 8%, p < 0.0001), appendicitis (1% vs. 0.4%, p < 0.0001) and other surgical complaints (1% vs. 0.5%, p < 0.0001) had proportional increases in the pandemic cohort. No significant proportional changes were noted among psychosocial and trauma groups between the two cohorts. CONCLUSION: The pandemic cohort experienced a substantial decrease in PED volume, but an increase in acuity and admission rates, which was sustained through the NYS phase-II re-opening. Despite being located in an asthma hub, the incidence of asthma-related PED visits declined appreciably in the pandemic cohort. Future studies examining the effects of indoor allergens in isolation on pediatric asthma are warranted.

Acyl-CoA subunit selectivity in the pikromycin polyketide synthase PikAIV: steady-state kinetics and active-site occupancy analysis by FTICR-MS.

Polyketide natural products generated by type I modular polyketide synthases (PKSs) are vital components in our drug repertoire. To reprogram these biosynthetic assembly lines, we must first understand the steps that occur within the modular "black boxes." Herein, key steps of acyl-CoA extender unit selection are explored by in vitro biochemical analysis of the PikAIV PKS model system. Two complementary approaches are employed: a fluorescent-probe assay for steady-state kinetic analysis, and Fourier Transform Ion Cyclotron Resonance-mass spectrometry (FTICR-MS) to monitor active-site occupancy. Findings from five enzyme variants and four model substrates have enabled a model to be proposed involving catalysis based upon acyl-CoA substrate loading followed by differential rates of hydrolysis. These efforts suggest a strategy for future pathway engineering efforts using unnatural extender units with slow rates of hydrolytic off-loading from the acyltransferase domain.