The repair of DNA double-strand breaks (DSB) is central to the maintenance of genomic integrity. In tumor cells, the ability to repair DSBs predicts response to radiation and many cytotoxic anti-cancer drugs. DSB repair pathways include homologous recombination and non-homologous end joining (NHEJ). NHEJ is a template-independent mechanism, yet many NHEJ repair products carry limited genetic changes, which suggests that NHEJ includes mechanisms to minimize error. Proteins required for mammalian NHEJ include Ku70/80, the DNA-dependent protein kinase (DNA-PKcs), XLF/Cernunnos and the XRCC4:DNA ligase IV complex. NHEJ also utilizes accessory proteins that include DNA polymerases, nucleases, and other end-processing factors. In yeast, mutations of tyrosyl-DNA phosphodiesterase (TDP1) reduced NHEJ fidelity. TDP1 plays an important role in repair of topoisomerase-mediated DNA damage and 3′-blocking DNA lesions, and mutation of the human TDP1 gene results in an inherited human neuropathy termed SCAN1. We found that human TDP1 stimulated DNA binding by XLF and physically interacted with XLF to form TDP1:XLF:DNA complexes. TDP1:XLF interactions preferentially stimulated TDP1 activity on dsDNA as compared to ssDNA. TDP1 also promoted DNA binding by Ku70/80 and stimulated DNA-PK activity. Because Ku70/80 and XLF are the first factors recruited to the DSB at the onset of NHEJ, our data suggest a role for TDP1 during the early stages of mammalian NHEJ.
We expanded health care services to economically disadvantaged individuals in an interprofessional, student-driven vaccination effort that also served as a pandemic planning drill. Health care professional students from colleges in and around Rockford, Illinois participated in implementing a mass vaccination event from 2011 to 2014 that targeted the underserved population. There was a 459% increase in total vaccinations administered to at-risk patients from year 1 to year 4. This interprofessional health care student-driven effort expanded medical service to disadvantaged individuals.
Extended-spectrum β-lactamases (ESBL) are produced mainly by members of the Enterobacteriaceae family and confer resistance to most β-lactam antibiotics. Because of limited treatment options, ESBL infections are typically more challenging to treat resulting in poor outcomes, increased complications, and mortality. Because ESBL-producing organisms are primarily seen in critically ill patients, along with those patients having prolonged hospital stays, extensive courses of antimicrobials, and/or use of invasive medical devices (i.e., urinary catheters, central venous lines, or endotracheal tubes), guidelines regarding the management of ESBL-producing organisms in the pediatric population are scant. A review of current recommended treatment options for infections caused by ESBL-producing organisms centers on the use of carbapenems, with some supportive literature regarding the utility/effectiveness of other non-β-lactam therapy. We present a case report of an 8-month-old female diagnosed with a urinary tract infection due to ESBL-producing Escherichia coli successfully treated with sulfamethoxazole/trimethoprim. Multidrug resistant infections in pediatric patients without risk factors remains an important field of study because these unique infections may pose a problem when choosing an effective empiric antimicrobial therapy.
Background and Objectives: Virtual interviews (VI) for residency programs present a relatively new paradigm for recruitment. To date, studies have been small, largely descriptive, and focused on surgical and subspecialty areas. The purpose of the study was to assess residents’ perceptions about their VI experience and to compare those in primary care versus non-primary care specialties. Methods: An electronic survey was sent to 35 designated institutional officials in Illinois with a resulting snowball sample to assess first-year residents’ perceptions of their virtual interviewing experience. A total of 82 postgraduate year-1 residents responded to the survey. We used descriptive analysis and χ2 tests to analyze results. Results: Respondents were mostly female (52.4%), White (79%), non-Hispanic (76%), attending a university residency program (76.3%), and in a primary care specialty (61.7%). In general, most respondents (54.8%-75.3%) felt their VI accurately portrayed their residency program experience. Resident morale, resident-faculty camaraderie, and educational opportunities were perceived as being best portrayed in the VI. Compared to non-primary care residents, primary care residents felt that their program’s VI more accurately portrayed the patient population served (P=.0184), resident morale in the program (P=.0038), and the overall residency experience (P=.0102). Still, 25.7% of respondents felt they were not accurately represented in the VI. Conclusions: Respondents reported that the VI portrays the residency experience fairly well, yet there is opportunity to improve the overall experience. The more difficult experiences to convey (morale, camaraderie, and the overall resident experience) may be areas in which primary care programs are outpacing other training programs.
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