Upon Ag exposure, naive B cells expressing BCR able to bind Ag can undergo robust proliferation and differentiation that can result in the production of Ab-secreting and memory B cells. The factors determining whether an individual naive B cell will proliferate following Ag encounter remains unclear. In this study, we found that polyclonal naive murine B cell populations specific for a variety of foreign Ags express high levels of the orphan nuclear receptor Nur77, which is known to be upregulated downstream of BCR signaling as a result of cross-reactivity with self-antigens in vivo. Similarly, a fraction of naive human B cells specific for clinically-relevant Ags derived from respiratory syncytial virus and HIV-1 also exhibited an IgMLOW IgD+ phenotype, which is associated with self-antigen cross-reactivity. Functionally, naive B cells expressing moderate levels of Nur77 are most likely to proliferate in vivo following Ag injection. Together, our data indicate that BCR cross-reactivity with self-antigen is a common feature of populations of naive B cells specific for foreign Ags and a moderate level of cross-reactivity primes individual cells for optimal proliferative responses following Ag exposure.
At the outset of the COVID-19 pandemic, many medical students were removed from clinical duties and had their education put on hold. Some found novel ways to join efforts to respond to the pandemic. Georgetown University School of Medicine medical students created Medical Supply Drive (MSD or MedSupplyDrive), a 501(c)(3), on March 17, 2020, in response to the national shortage of personal protective equipment (PPE). This article reviews the formation of a national response to the pandemic, the methods employed to distribute PPE, and the results of MSD's work from March 17, 2020, through June 20, 2020. A focus was placed on equitable distribution, both within
BackgroundThe prevalence of syphilis is increasing in many countries, including the USA. The ED is often used by underserved populations, making it an important setting to test and treat patients who are not evaluated in outpatient clinical settings. We aimed to assess the utility of an ED-based syphilis and gonorrhoea/chlamydia cotesting protocol by comparing testing practices before and after its implementation.MethodsWe implemented an electronic health record (EHR) alert that prompted clinicians to order syphilis testing in patients undergoing gonorrhoea/chlamydia testing. We performed a retrospective cohort analysis that compared outcomes between the preimplementation period (January–November 2018) and the postimplementation period (January–November 2019). Patients were tested for Treponema pallidum antibody (TPA) using a multiplex flow immunoassay (MFI), and positive results were confirmed by rapid plasma reagin (RPR). The primary implementation outcome was the number of syphilis tests/month, and the primary clinical outcome was the number of syphilis diagnoses/month (defined as positive TPA MFI and RPR). We performed an interrupted time-series analysis to evaluate the effect of implementing the alert over time.ResultsFour-hundred and ninety-four and 1106 unique patients were tested for syphilis in the preimplementation and postimplementation periods, respectively. Syphilis testing increased by 55.6 tests/month (95% CI 45.9 to 65.3, p<0.001) following alert implementation. Patients tested in the postimplementation period who were tested using the alert were much younger (difference: 14 years (95% CI 12 to 15)) and were more likely to be female (difference: 15% (95% CI 8 to 21)) and African-American (difference: 11% (95% CI 5 to 17)) than patients tested by clinician-initiated testing. Presumptive syphilis diagnoses increased from 3.4 diagnoses/month to 7.9 diagnoses/month (difference, 4.5 (95% CI 2.2 to 6.9), p<0.001).ConclusionsOur study demonstrates that use of a targeted EHR alert testing protocol can increase syphilis testing and diagnosis and may reduce clinician bias in testing.
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