Real-Time Peer-to-Peer Observation and Feedback Lead to Improvement in Oral Presentation Skills.

Background Oral case presentation is a vital skill in many fields, particularly in medicine, and is taught early on in medical schools. However, there is a diminished focus on the development of this skill during the clinical years. In this study, we investigated whether the implementation of a formal teaching strategy during the internal medicine clerkship rotation can lead to an improvement in oral presentation skills. Methodology Students received an introductory PowerPoint lecture and saw brief video presentations summarizing the key components of a successful oral presentation. Subsequently, students were asked to evaluate their peers while they presented during morning rounds using a standardized feedback form in the first and the second half of their rotation. Using the information gained from the feedback form, students provided verbal feedback on the quality of oral presentations to their peers. Results A total of 64 students participated in this curriculum at a university-affiliated teaching hospital, and a total of 409 evaluations were completed. The average total score during the first and the second rotation period was 93.0% (standard deviation, SD = 9.8) and 96.9% (SD = 7.1), respectively. Improvement in the total score of 3.7% points was seen in the entire cohort, with an average improvement of 64% (or 1.64 times) in the probability of obtaining a full score during the second rotation. Conclusions Our data show improvement in scores between collection blocks using an educational strategy. This study emphasizes the fact that peer-to-peer evaluations helped in the refinement of oral presentation skills.

Severe Vitamin B12 Deficiency Mimicking Microangiopathic Hemolytic Anemia.

Most individuals with vitamin B12 deficiency present with anemia, fatigue, and neurologic disturbances such as paresthesia and loss of sensory function if chronic. However, in severe states, it may manifest as hemolytic anemia, thrombocytopenia, schistocytosis, elevated lactate dehydrogenase, and low reticulocyte production. This phenomenon is known as pseudo-thrombotic microangiopathy (TMA), and is most commonly due to pernicious anemia. The overlap in clinical presentation with primary TMA creates a challenge in the diagnosis and management of pseudo-TMA. Primary TMA, particularly thrombotic thrombocytopenic purpura, is emergently managed with plasma exchange and may require admission to an intensive care unit due to high risk of mortality. In contrast, pseudo-TMA does not respond to plasma exchange and instead is treated with vitamin B12 supplementation. Patients with this atypical presentation of B12 deficiency may receive unnecessary, costly, and potentially harmful therapy. We present the case of a patient with pseudo-TMA in the setting of pernicious anemia.

Targeting of multiple signaling pathways by the Hsp90 inhibitor SNX-2112 in EGFR resistance models as a single agent or in combination with erlotinib.

Inhibition of Hsp90 has emerged as a therapeutic strategy to target NSCLC subtypes, which are refractory to epidermal growth factor receptor (EGFR) inhibitor-based treatment. We report on a novel small molecule inhibitor of Hsp90, SNX-2112, and an orally bioavailable prodrug analog, SNX-5422. In cellular models of wild-type or mutant EGFR (L858R and T790M mutations), SNX-2112 alone and in combination with erlotinib inhibited EGF activation of pAKT(473) and pSTAT3(705). pERK1/2 and pS6 were also potently inhibited by similar treatments. SNX-2112 reduced EGF cross-talk and activation of the c-Met receptor by causing c-Met degradation. In NCI-H1975 xenograft models, SNX-5422 showed activity as a single agent and in combination with erlotinib resulted in prolonged animal survival at reduced compound concentrations relative to either compound alone. These results support the advanced evaluation of SNX-5422 as a treatment for non-small cell lung cancer (NSCLC), especially in cases where the cancer is driven by c-Met amplification or mutated EGFR forms that are resistant to EGFR inhibitors.

Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90.

A chemoproteomics-based drug discovery strategy is presented that utilizes a highly parallel screening platform, encompassing more than 1000 targets, with a focused chemical library prior to target selection. This chemoproteomics-based process enables a data-driven selection of both the biological target and chemical hit after the screen is complete. The methodology has been exemplified for the purine binding proteome (proteins utilizing ATP, NAD, FAD). Screening of an 8000 member library yielded over 1500 unique protein-ligand interactions, which included novel hits for the oncology target Hsp90. The approach, which also provides broad target selectivity information, was used to drive the identification of a potent and orally active Hsp90 inhibitor, SNX-5422, which is currently in phase 1 clinical studies.

Murine CD7 shares antigenic cross-reactivity with HSP-60.

Human (h) CD7 is a 40 kDa single chain Ig superfamily molecule that is expressed on thymocytes, a major subunit of peripheral T cells, and most natural killer cells. Ligands for hCD7 include the epithelial cell-produced molecule, K-12, and galectin. Mice deficient in CD7 have been shown to be resistant to LPS-induced endotoxic shock syndromes. However, monoclonal antibodies (MAb) to mouse (m) CD7 have yet to be produced, nor is the distribution of mCD7 protein in mice known. We have raised a panel of three rat MAbs to mCD7 by immunizing rats with recombinant mCD7 protein. However, using Western blot and immunoprecipitation of tissue extracts from mouse thymus, spleen, liver, brain, lymph node and skin, these anti-mouse CD7 MAbs bound only to murine heat shock protein 60 (HSP-60) present both in wild-type (CD7+/+) and CD7-deficient (CD7-/-) mice. Epitope mapping of the sites on HSP-60 and recombinant mCD7 recognized by mCD7 MAbs demonstrated non-homologous amino acid sequence epitopes recognized by anti-CD7 MAbs on both proteins. These data demonstrated molecular mimicry of mCD7 with HSP-60, and leave open the question of surface expression of mCD7.

Discovery of novel targets of quinoline drugs in the human purine binding proteome.

The quinolines have been used in the treatment of malaria, arthritis, and lupus for many years, yet the precise mechanism of their action remains unclear. In this study, we used a functional proteomics approach that exploited the structural similarities between the quinoline compounds and the purine ring of ATP to identify quinoline-binding proteins. Several quinoline drugs were screened by displacement affinity chromatography against the purine binding proteome captured with gamma-phosphate-linked ATP-Sepharose. Screening of the human red blood cell purine binding proteome identified two human proteins, aldehyde dehydrogenase 1 (ALDH1) and quinone reductase 2 (QR2). In contrast, no proteins were detected upon screening of the Plasmodium falciparum purine binding proteome with the quinolines. In a complementary approach, we passed cell lysates from mice, red blood cells, or P. falciparum over hydroxychloroquine- or primaquine-Sepharose. Consistent with the displacement affinity chromatography screen, ALDH and QR2 were the only proteins recovered from mice and human red blood cell lysate and no proteins were recovered from P. falciparum. Furthermore, the activity of QR2 was potently inhibited by several of the quinolines in vitro. Our results show that ALDH1 and QR2 are selective targets of the quinolines and may provide new insights into the mechanism of action of these drugs.