miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation of leukemic blasts, and induced cell death. Antagonism of miR-196b activity or pharmacologic inhibition of the Cks1-Skp2–containing SCF E3-ubiquitin ligase complex increased p27Kip1 and inhibited human AML growth. This work illustrates that understanding oncogenic miRNA target pathways can identify actionable targets in leukemia

Character, Incidence, and Predictors of Knee Pain and Activity after Infrapatellar Intramedullary Nailing of an Isolated Tibia Fracture

© Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved. Objective: To study the activity and incidence of knee pain after sustaining an isolated tibia fracture treated with an infrapatellar intramedullary nail at 1 year. Design: Retrospective review of prospective cohort. Setting: Multicenter Academic and Community hospitals. Patients: Four hundred thirty-seven patients with an isolated tibia fracture completed a 12-month assessment on pain and self-reported activity. Intervention: Infrapatellar intramedullary nail. Outcomes: Demographic information, comorbid conditions, injury characteristics, and surgical technique were recorded. Knee pain was defined on a 1-7 scale with 1 being no pain and 7 being a very great deal of pain. Knee pain \u3e4 was considered clinically significant. Patients reported if they were able, able with difficulty, or unable to perform the following activities: kneel, run, climb stairs, and walk prolonged. Variables were tested in multilevel multivariable regression analyses. Results: In knee pain, 11% of patients reported a good deal to a very great deal of pain (\u3e4), and 52% of patients reported no or very little pain at 12 months. In activity at 12 months, 26% and 29% of patients were unable to kneel or run, respectively, and 31% and 35% of patients, respectively, stated they were able with difficulty or unable to use stairs or walk. Conclusions: Clinically significant knee pain (\u3e4/7) was present in 11% of patients 1 year after a tibia fracture. Of note, 31%-71% of patients had difficulty performing or were unable to perform routine daily activities of kneeling, running, and stair climbing, or walking prolonged distances

Comparing G-Force Measurement Between a Smartphone App and an In-Vehicle Accelerometer

Due to their widespread adoption, smartphone applications (apps) could allow for a simple, low-cost assessment of driving behavior on a population scale. A number of existing apps are capable of measuring g-forces while driving, but few evaluations have been conducted to determine their accuracy. The goal of this study was to compare the measurement of g-forces between two devices: a custom-built smartphone app and an in-vehicle device that is currently used for research purposes (DAS). The test occurred under experimental conditions on a test track, where a vehicle, equipped with both the DAS and a smartphone with the app installed, performed a number of different acceleration events (e.g. hard-braking, sharp turning, etc.) under controlled conditions. We found that the app captured data that followed the same overall pattern of the DAS, but had a lower amplitude of measurement and a lower signal-to-noise ratio in the data. In general, the strength of the association between the app and DAS improved as the velocity of the events increased (though this was not true for all maneuvers). The correlations between the app and DAS were weaker for other maneuvers, and this may be due to delays in registering the maneuver. These findings indicate that a smartphone application did not register driving maneuvers in the same way that a dedicated in-vehicle device recorded them. Smartphones are ubiquitous and could represent a valuable driving research tool, however steps such as validation and testing are required, before they can be deployed in field trials

State University of New York at Brockport

Chronicles the history of a highly respected public college in western New York State. Founded by Erie Canal entrepreneurs as a Baptist college in 1835, the institution became an academy in 1841, a state-funded normal school in 1867, a state teachers college in 1941, and finally the comprehensive college, within the nation\u27s largest public university system, that it is today. The post-World War II era witnessed two bursts of dramatic enrollment growth, one underwritten by the 1944 GI Bill, the other inspired by local initiatives and expansive state funding in the late 1960s and early 1970s. The college\u27s selection to host the 1979 International Special Olympics concluded a 20-year period of dynamic innovation. In the 1980s, the college struggled to adjust to reduced public funding and declining enrollments before achieving stability and regaining its solid reputation.The authors have collectively have served The College at Brockport for over three-quarters of a century: Mary Jo Gigliotti was the college archivist; W. Bruce Leslie, a social historian, specializes in the history of higher education; and Kenneth P. O\u27Brien, former Monroe County historian, is a modern American historian.https://digitalcommons.brockport.edu/bookshelf/1059/thumbnail.jp