Investigating the Regulation of bS21 Homologs in Francisella tularensis

Sierra Schmidt, Aisling Macaraeg, Dan Floyd, Hannah Trautmann, Kathryn Ramsey

Francisella tularensis is a highly infectious, intracellular human pathogen that can cause fatal disease. The F. tularensis type VI secretion system is an essential virulence factor required for survival in host cells, including survival in what are considered a key niche, macrophage. We have determined that ribosome composition influences production of the F. tularensis type VI secretion system and virulence. Ribosomes containing one of the three homologs for the small ribosomal subunit protein bS21, bS21-2, positively control key virulence genes and intramacrophage replication. However, the mechanisms that control and coordinate production of bS21-2 and the other bS21 homologs, bS21-1 and bS21-3, are unknown. We have found that bS21-2 negatively regulates its own production, as the presence of bS21-2 leads to significant reductions in abundance of its transcript, rpsU2. Further, we have found that the 5′ untranslated region (UTR) of rpsU2 is sufficient for this bS21-2-mediated repression. Production of bS21-2 appears to be tightly controlled by bS21 levels in the cell, as both bS21-1 and bS21-3 also negatively regulate bS21-2 transcript abundance. In contrast, bS21-1 and bS21-3 do not affect their own production. Thus, the bS21-mediated regulation of bS21-2 appears to be unique among the three homologs. This suggests that F. tularensis integrates multiple signals into a regulatory network to control the appropriate production of each bS21 homolog. This regulatory network in turn may control ribosomal heterogeneity and virulence gene expression.

Prescription Opioid Dispensing in Medicare Part D in 2020 by US Region and Generalist/Specialist Prescribers

Ravi Y. Upadhyay, Stephen Kogut

Background: Increased national attention is directed to opioid prescribing among generalist physicians.

Methods: We analyzed the Medicare Part D Prescribers by Provider and Drug dataset to determine the number of opioid claims per Medicare enrollee for US 2020 and the percentage of opioid claims by provider type.

Results: Part D prescription opioid claims ranged from 0.566 to 2.129 per enrollee across US states during 2020. Alabama led among 50 US states the with highest annual rates of Part D prescription opioid claims for the year 2020. Whereas Hawaii shows the lowest rates among 50 states annual rates of Part D prescription opioid claims. Higher rates of prescription opioid claims were observed for the US South among the 4 US census regions. General medical practitioners prescribed opioids approximately as many as 3 times higher than those specialty practitioners in Vermont, Iowa, Maine, Mississippi, and Tennessee. Vermont had the highest percentage of opioids issued by generalist providers at 76%. Florida had the lowest percentage of opioids issued by generalist providers at 38%.

Conclusion: Using a national sample of Medicare beneficiaries, we observed that during the year 2020, the use of prescription opioid claims was highest in Alabama and lowest in Hawaii, while the percentage of opioids prescribed by generalist providers varied widely across US states.