Constitutional chromosomal translocations are relatively common causes of human morbidity, yet the DNA double-strand break (DSB) repair mechanisms that generate them are incompletely understood. We cloned, sequenced and analyzed the breakpoint junctions of a familial constitutional reciprocal translocation t(9;11)(p24;q23). Within the 10-kb region flanking the breakpoints, chromosome 11 had 25% repeat elements, whereas chromosome 9 had 98% repeats, 95% of which were L1-type LINE elements. The breakpoints occurred within an L1-type repeat element at 9p24 and at the 3'-end of an Alu sequence at 11q23. At the breakpoint junction of derivative chromosome 9, we discovered an unusually large 41-bp insertion, which showed 100% identity to 12S mitochondrial DNA (mtDNA) between nucleotides 896 and 936 of the mtDNA sequence. Analysis of the human genome failed to show the preexistence of the inserted sequence at normal chromosomes 9 and 11 breakpoint junctions or elsewhere in the genome, strongly suggesting that the insertion was derived from human mtDNA and captured into the junction during the DSB repair process. To our knowledge, these findings represent the first observation of spontaneous germ line insertion of modern human mtDNA sequences and suggest that DSB repair may play a role in inter-organellar gene transfer in vivo. Our findings also provide evidence for a previously unrecognized insertional mechanism in human, by which non-mobile extra-chromosomal fragments can be inserted into the genome at DSB repair junctions.

No abstract

It is well established that retention in high-quality care and regular visits with an HIV/AIDS provider improve outcomes for people living with HIV/AIDS (PLWHA). However, nationally and regionally in South Carolina, retention rates remain low. We piloted an outreach program focused on characterizing out of care (OOC) patients to identify PLWHA who were lost to care and attempt reengagement through phone call, letter, and home visit interventions. Primary outcomes were reengagement, defined as attendance to a clinic appointment, and retention in care, defined by the Health Resources and Services Administration (HRSA) definition (two visits at least 90 days apart in 2015). There were 1242 adult clinic patients in 2014. A total of 233 patients were included in the OOC cohort, according to the inclusion criteria. Of these 233, the outreach coordinator found that a majority of patients, 119 (51%), were lost to care. Reengagement was seen in 52 (44%) patients lost to care, and among those who reengaged, 26 (50%) were retained in care in 2015. This report represents one of few interventions that target reengagement for patients who are lost to care. The use of an outreach coordinator was successful in reengaging and retaining patients in care. It represents an uncomplicated intervention, functional within the current clinic design and available funding structure of the Ryan White grant. Poor engagement and retention in care continue to be significant problems among PLWHA with resultant poor clinical outcomes. Continued focus on new interventions to improve retention in care is necessary to improve clinical outcomes.

Our work shows that cricothyroidotomy skills taught to anesthesia residents at SPHMMC with a 3D printed laryngotracheal model improves knowledge, skills, and confidence. The creation of a low-cost, high-fidelity simulator and a CSMP has the potential to impact patient care and safety world-wide.