Diagnosis of Pediatric Non-Esophageal Eosinophilic Gastrointestinal Disorders by Eosinophil Peroxidase Immunohistochemistry.

BACKGROUND: Diagnosis of non-esophageal eosinophilic gastrointestinal disorders requires quantification of tissue eosinophils. Our objective was to evaluate eosinophil peroxidase (EPX) immunohistochemistry (IHC) as a method for histologic diagnosis of eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD). METHODS: We performed a retrospective analysis of biopsies from pediatric EG/EoD cases and controls. Subjects with EG or EoD had ≥30 eosinophils per high power field (eos/hpf) in ≥5 hpf in the stomach and/or ≥3 hpf in the duodenum, respectively. Controls had no histopathologic diagnosis recorded. Tissue eosinophil counts were assessed by hematoxylin & eosin stains. EPX stains were assessed using a unique histopathologic scoring system. Slides were digitized and EPX+ staining area/mm2 was quantified by image analysis. RESULTS: Twenty-six EG/EoD cases and 40 controls were analyzed. EPX scores and EPX/mm2 levels were markedly elevated in EG/EoD (p ≤ 0.0001). Eosinophil density (eos/mm2) correlated strongly with EPX scores and EPX/mm2 levels in the stomach (r ≥ 0.77) and moderately with EPX scores and EPX/mm2 levels in the duodenum (r ≥ 0.52); (p < 0.0001). EPX quantification identified EG/EoD subjects with high diagnostic accuracy (EPX score: AUC = 1 for EG and EoD; EPX/mm2: AUC = 0.98 (95%CI 0.96-1) for EG, AUC = 0.91 (95%CI 0.81-1) for EoD). CONCLUSION: EPX-based assessment of eosinophilic inflammation may facilitate automated histologic diagnosis.

Out-of-State Students at State Medical Schools and Increasing Medical Education Debt.

PURPOSE: Medical school tuition has increased at alarming rates ahead of inflation over the past 20 years. The authors investigated whether state-funded medical schools have had an increased number of out-of-state matriculants, which may create a diaspora of displaced in-state medical students matriculating to out-of-state programs and incurring substantial debt. METHOD: Publicly available data from the Association of American Medical Colleges (AAMC) were accessed from 2004 through 2019 for applicants and matriculants at U.S. state-funded schools. Schools listed as public that reported tuition charges in the AAMC Tuition and Student Fees reports were included in this study. The numbers and trends of medical school applications and trends in tuition costs and average indebtedness were summarized for in-state and out-of-state matriculants. Values were analyzed by group as median and interquartile range (IQR). Group differences were assessed via t tests. P values less than .05 were considered statistically significant. RESULTS: From 2004 through 2019, the annual number of out-of-state matriculants in state-funded schools increased 7% (16%-23% [7,195-11,144]). Among 74 schools with data in 2004, the median percentage of out-of-state applications increased from 60% (IQR, 31%-74%) to 80% (IQR, 57%-85%; P < .001), and the median percentage of out-of-state matriculants increased from 13% (IQR, 5%-23%) to 17% (IQR, 11%-33%; P < .001). In 2004, the mean (standard error) debt upon completion of medical school (inflation adjusted to 2018 dollars) was $144,100 ($10,950); by 2016, the mean debt had increased to $251,600 ($32,040), a 75% increase over 12 years. CONCLUSIONS: Since 2004, substantial increases have occurred in out-of-state matriculants at state-funded medical schools. This may displace residents from attending their in-state schools, causing them to attend out-of-state or private medical schools, where tuition is typically much higher.

Mechanism of RNA polymerase III termination-associated reinitiation-recycling conferred by the essential function of the N terminal-and-linker domain of the C11 subunit.

RNA polymerase III achieves high level tRNA synthesis by termination-associated reinitiation-recycling that involves the essential C11 subunit and heterodimeric C37/53. The C11-CTD (C-terminal domain) promotes Pol III active center-intrinsic RNA 3'-cleavage although deciphering function for this activity has been complicated. We show that the isolated NTD (N-terminal domain) of C11 stimulates Pol III termination by C37/53 but not reinitiation-recycling which requires the NTD-linker (NTD-L). By an approach different from what led to current belief that RNA 3'-cleavage activity is essential, we show that NTD-L can provide the essential function of Saccharomyces cerevisiae C11 whereas classic point mutations that block cleavage, interfere with active site function and are toxic to growth. Biochemical and in vivo analysis including of the C11 invariant central linker led to a model for Pol III termination-associated reinitiation-recycling. The C11 NTD and CTD stimulate termination and RNA 3'-cleavage, respectively, whereas reinitiation-recycling activity unique to Pol III requires only the NTD-linker. RNA 3'-cleavage activity increases growth rate but is nonessential.