Naegleria fowleri is a pathogenic, thermophilic, free-living amoeba which causes primary amebic meningoencephalitis (PAM). Penetrating the olfactory mucosa, the brain-eating amoeba travels along the olfactory nerves, burrowing through the cribriform plate to its destination: the brain’s frontal lobes. The amoeba thrives in warm, freshwater environments, with peak infection rates in the summer months and has a mortality rate of approximately 97%. A major contributor to the pathogen’s high mortality is the lack of sensitivity of N. fowleri to current drug therapies, even in the face of combination-drug therapy. To enable rational drug discovery and design efforts we have pursued protein production and crystallography-based structure determination efforts for likely drug targets from N. fowleri. The genes were selected if they had homology to drug targets listed in Drug Bank or were nominated by primary investigators engaged in N. fowleri research. In 2017, 178 N. fowleri protein targets were queued to the Seattle Structural Genomics Center of Infectious Disease (SSGCID) pipeline, and to date 89 soluble recombinant proteins and 19 unique target structures have been produced. Many of the new protein structures are potential drug targets and contain structural differences compared to their human homologs, which could allow for the development of pathogen-specific inhibitors. Five of the structures were analyzed in more detail, and four of five show promise that selective inhibitors of the active site could be found. The 19 solved crystal structures build a foundation for future work in combating this devastating disease by encouraging further investigation to stimulate drug discovery for this neglected pathogen.

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Background The number of for-profit hospitals has increased in the United States, but their role in and outcomes for graduate medical education (GME) are unclear. Objectives To describe for-profit involvement in internal medicine (IM), general surgery (GS), and pediatrics GME by quantifying change in for-profit affiliated residency programs and comparing for-profit and nonprofit affiliated program board certifying examination pass rates. Methods We used Accreditation Council for Graduate Medical Education and Medicare data to quantify for-profit prevalence in IM, GS, and pediatrics GME from 2001 to 2021. We used public pass rate data from the American Board of Surgeons (2017-2019; n=242 programs; 6562 examinees), American Board of Internal Medicine (2018-2020; n=465 programs; 23 922 examinees), and American Board of Pediatrics (2018-2020; n=202 programs; 9819 examinees) to model the relationship between profit status and pass rate within each specialty and across specialties combined using linear regression. Results The proportion of for-profit affiliated residency programs increased 400.0% in IM, 334.4% in GS, and 23.2% in pediatrics from 2001 to 2021. Bivariate linear regression revealed significantly lower pass rate in for-profit affiliated programs in IM β =-7.73, P<.001), pediatrics (β =-14.6, P<.001), and the 3 specialties combined (β =-5.45, P<.001). Upon multiple regression with addition of program characteristic covariates, this relationship remained significant in pediatrics (β =-10.04, P=.006). Conclusions The proportion of for-profit affiliated residency programs has increased in IM, GS, and pediatrics from 2001 to 2021. After controlling for covariates, for-profit affiliated programs were associated with lower board examination pass rates in pediatrics with no association in IM, GS, or the combined measure.

Naegleria fowleri is a pathogenic, thermophilic, free-living amoeba which causes primary amebic meningoencephalitis (PAM). Penetrating the olfactory mucosa, the brain-eating amoeba travels along the olfactory nerves, burrowing through the cribriform plate to its destination: the brain's frontal lobes. The amoeba thrives in warm, freshwater environments, with peak infection rates in the summer months and has a mortality rate of approximately 97%. A major contributor to the pathogen's high mortality is the lack of sensitivity of N. fowleri to current drug therapies, even in the face of combination-drug therapy. To enable rational drug discovery and design efforts we have pursued protein production and crystallography-based structure determination efforts for likely drug targets from N. fowleri. N. fowleri genes were selected if they had homology to drug targets listed in Drug Bank or were nominated by primary investigators engaged in N. fowleri research. In 2017, 178 N. fowleri protein targets were queued to the Seattle Structural Genomics Center of Infectious Disease (SSGCID) pipeline, and to date 89 soluble recombinant proteins and 19 unique target structures have been produced. Many of the new protein structures are potential drug targets and contain structural differences compared to their human homologs, which could allow for the development of pathogen-specific inhibitors. Five of the structures were analyzed in more detail, and four of five show promise that selective inhibitors of the active site could be found. The 19 solved crystal structures build a foundation for future work in combating this devastating disease by encouraging further investigation to stimulate drug discovery for this neglected pathogen.

Introduction: Advanced practice providers (APPs), such as nurse practitioners and physician assistants, are a growing part of urology practices. However, the impact of APPs on improving new patient access in urology is unknown. We examined the impact of APPs on new patient wait times in a real-world sample of urology offices.Methods: Research assistants posing as caretakers called urology offices in the Chicago metropolitan area and attempted to schedule a new patient appointment for an elderly grandparent with gross hematuria. Appointments were requested with any available provider: physician or APP. Descriptive measurements of clinic characteristics were reported and differences in appointment wait times were determined using negative binomial regressions.Results: Of the 86 offices with which we scheduled appointments, 55 (64%) employed at least 1 APP but only 18 (21%) allowed for new patient appointments with APPs. When requested for the earliest appointment regardless of provider type, offices with APPs could offer shorter wait times compared to physician-only offices (10 vs 18 days; p¼0.09). Initial appointments with an APP were available with a significantly shorter wait than those with a physician (5 days vs 15 days; p¼0.04).Conclusions: Urology offices are commonly employing APPs but giving them a limited role in new patient visits. This suggests that offices with APPs may have an unrealized opportunity to improve new patient access. Further work is needed to better elucidate the role of APPs in these offices and how they might best be deployed.