Predicting Quality of Clinical Performance From Cardiology Fellowship Applications

Variables in cardiology fellowship applications have not been objectively analyzed against applicants\u27 subsequent clinical performance. We investigated possible correlations in a retrospective cohort study of 65 cardiology fellows at the Mayo Clinic (Rochester, Minn) who began 2 years of clinical training from July 2007 through July 2013. Application variables included the strength of comparative statements in recommendation letters and the authors\u27 academic ranks, membership status in the Alpha Omega Alpha Honor Medical Society, awards earned, volunteer activities, United States Medical Licensing Examination (USMLE) scores, advanced degrees, publications, and completion of a residency program ranked in the top 6 in the United States. The outcome was clinical performance as measured by a mean of faculty evaluation scores during clinical training. The overall mean evaluation score was 4.07 ± 0.18 (scale, 1-5). After multivariable analysis, evaluation scores were associated with Alpha Omega Alpha designation (β=0.13; 95% CI, 0.01-0.25; P=0.03), residency program reputation (β=0.13; 95% CI, 0.05-0.21; P=0.004), and strength of comparative statements in recommendation letters (β=0.08; 95% CI, 0.01-0.15; P=0.02), particularly in letters from residency program directors (β=0.05; 95% CI, 0.01-0.08; P=0.009). Objective factors to consider in the cardiology fellowship application include Alpha Omega Alpha membership, residency program reputation, and comparative statements from residency program directors

Complementary activities of DOT1L and Menin inhibitors in MLL-rearranged leukemia

Chromosomal rearrangements of the mixed lineage leukemia (MLL/KMT2A) gene leading to oncogenic MLL-fusion proteins occur in ~10% of acute leukemias and are associated with poor clinical outcomes, emphasizing the need for new treatment modalities. Inhibition of the DOT1-like histone H3K79 methyltransferase (DOT1L) is a specific therapeutic approach for such leukemias that is currently being tested in clinical trials. However, in most MLL-rearranged leukemia models responses to DOT1L inhibitors are limited. Here, we performed deep-coverage short hairpin RNA sensitizer screens in DOT1L inhibitor-treated MLL-rearranged leukemia cell lines and discovered that targeting additional nodes of MLL complexes concomitantly with DOT1L inhibition bears great potential for superior therapeutic results. Most notably, combination of a DOT1L inhibitor with an inhibitor of the MLL-Menin interaction markedly enhanced induction of differentiation and cell killing in various MLL disease models including primary leukemia cells, while sparing normal hematopoiesis and leukemias without MLL rearrangements. Gene expression analysis on human and murine leukemic cells revealed that target genes of MLL-fusion proteins and MYC were suppressed more profoundly upon combination treatment. Our findings provide a strong rationale for a novel targeted combination therapy that is expected to improve therapeutic outcomes in patients with MLL-rearranged leukemia.Leukemia advance online publication, 3 January 2017; doi:10.1038/leu.2016.327

ALBA proteins are stage regulated during trypanosome development in the tsetse fly and participate in differentiation

The protozoan parasite Trypanosoma brucei is responsible for sleeping sickness and alternates between mammal and tsetse fly hosts. Two proteins of the ALBA family associate to mRNA in cytoplasmic granules during starvation stress, are stage regulated, and contribute to trypanosome development in the tsetse fly