Background Altered expression of microRNAs (miRNAs) is known to contribute to cancer progression. miR-23b and miR-27b, encoded within the same miRNA cluster, are reported to have both tumor suppressive and oncogenic activity across human cancers, including breast cancer. Methods To clarify this dichotomous role in breast cancer, miR-23b and miR-27b were knocked out using CRISPR/Cas9 gene knockout technology, and the role of endogenous miR-23b and miR-27b was examined in a breast cancer model system in vitro and in vivo. Results Characterization of the knockout cells in vitro demonstrated that miR-23b and miR-27b are indeed oncogenic miRNAs in MCF7 breast cancer cells. miR-23b and miR-27b knockout reduced tumor growth in xenograft nude mice fed a standard diet, supporting their oncogenic role in vivo. However, when xenograft mice were provided a fish-oil diet, miR-27b depletion, but not miR-23b depletion, compromised fish-oil-induced suppression of xenograft growth, indicating a context-dependent nature of miR-27b oncogenic activity. Conclusions Our results demonstrate that miR-23b and miR-27b are primarily oncogenic in MCF7 breast cancer cells and that miR-27b may have tumor suppressive activity under certain circumstances.

In this paper, we report ultrasonically-active nanoscale contrast agents that behave as thermometric sensors through phase change in their stabilizing phospholipid monolayer. Phospholipid-stabilized, hydrophobic mesoporous silica nanoparticles (P@hMSNs) are known to interact with high intensity focused ultrasound (HIFU) to promote cavitation at their surfaces, which can be used for both imaging and therapy. We show that the lateral lipid phase behavior of the phosphocholine lipid dictates the acoustic contrast of the P@hMSNs. When the lipids are in gel phase below their melting temperature, the P@hMSNs generate detectable microbubbles when exposed to HIFU. However, if the lipids exhibit a liquid expanded phase, the P@hMSNs cease to generate bubbles in response to HIFU insonation. We verify that the heating and subsequent transition of lipid coating the hMSN is associated with the loss of acoustic response by doping laurdan dye into the lipid monolayer and imaging lipid phase through red shifts in emission spectra. Similarly, cessation of cavitation was also induced by adding a fluidizing surfactant such as Triton X, which could be reversed upon washing away excess surfactant. Finally, by controlling for the partial fluidization caused by the adsorption of protein, P@hMSNs may be used as thermometric sensors of bulk fluid temperature. These findings not only impact the utilization of nanoscale agents as stimulusresponsive ultrasound contrast agents, but also have broader implications for how cavitation may be initiated at surfaces coated by a surfactant.

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Physicians believe that malpractice concerns result in unnecessary testing, and many emergency physicians state that avoiding malpractice is a contributing factor to ordering medically unnecessary tests. Unfortunately, defensive medicine does not come without possible harm to patients who may be subject to non-beneficial, downstream testing, procedures, and hospitalizations. We submit a novel statistic, "NUTS" or "Number of Unnecessary Tests to avoid one Suit. " We calculated a NUTS of 4737 for troponin testing in ED patients with suspected myocardial infarction, meaning a clinician will need to order 4737 medically unnecessary troponin tests to avoid one missed myocardial infarction lawsuit. The NUTS framework offers us an evidence-based lens to examine defensive medicine less superstitiously and more based on currently available data.