Keeping busy learners informed: email is most useful for medical residents!

Background: Educators need to ensure trainees have access to the rotation orientation information they need in the most effective way possible. We wanted to find the best method to distribute this information. Methods: We provided post-graduate medical trainees rotating through the Pediatric Emergency Medicine program at the Children’s Hospital of Eastern Ontario in Ottawa, Canada, the regular rotation information package three ways: email, online, and paper. We surveyed them to find out which method(s) they used and which they found most useful. Results: All traineeswere able to access the electronic orientation package via email and most found this method useful. Most also found the paper package distributed at the orientation helpful. Few accessed the online wiki site. Conclusion: Using email is efficient and effective and can save both the time and cost of producing paper packages. The wiki site was not used frequently in our cohort, but may be worth future exploration

KDM4B is a master regulator of the estrogen receptor signalling cascade

The importance of the estrogen receptor (ER) in breast cancer (BCa) development makes it a prominent target for therapy. Current treatments, however, have limited effectiveness, and hence the definition of new therapeutic targets is vital. The ER is a member of the nuclear hormone receptor superfamily of transcription factors that requires co-regulator proteins for complete regulation. Emerging evidence has implicated a small number of histone methyltransferase (HMT) and histone demethylase (HDM) enzymes as regulators of ER signalling, including the histone H3 lysine 9 tri-/di-methyl HDM enzyme KDM4B. Two recent independent reports have demonstrated that KDM4B is required for ER-mediated transcription and depletion of the enzyme attenuates BCa growth in vitro and in vivo. Here we show that KDM4B has an overarching regulatory role in the ER signalling cascade by controlling expression of the ER and FOXA1 genes, two critical components for maintenance of the estrogen-dependent phenotype. KDM4B interacts with the transcription factor GATA-3 in BCa cell lines and directly co-activates GATA-3 activity in reporter-based experiments. Moreover, we reveal that KDM4B recruitment and demethylation of repressive H3K9me3 marks within upstream regulatory regions of the ER gene permits binding of GATA-3 to drive receptor expression. Ultimately, our findings confirm the importance of KDM4B within the ER signalling cascade and as a potential therapeutic target for BCa treatment

PKM2 expression in human HCC.

<p>(A) mRNA expression of PKL, PKM1, and PKM2 in HCC and NT tissues. Values = 2^ΔΔCT, ΔΔCT = (CT_PK – CT_HPRT) of HCC - (CT_PK– CT_HPRT) of NT. <i>P</i> values, Wilcoxin signed rank test (B) Waterfall plot shows that, at the mRNA level, PKM2 was up-regulated (HCC/NT2 folds) in 29/60 (48.33%) human HCC samples. (C) Representative pictures of IHC staining with antibody against PKM2 in HCC tissue microarray. PKM2 protein was drastically up-regulated in human HCCs as compared to the paired NT tissues. (D) Mann Whitney test showed that PKM2 over-expression was associated with multiple aggressive clinicopathological features in HCC including the presence of tumor microsatellites, presence of venous invasion, and absence of tumor encapsulation. (E) Over-expression of PKM2 in human HCC was associated with poor prognosis. HCC patients were categorized into two groups: PKM2 over-expression and PKM2 normal/under-expression. PKM2 was considered to be over-expressed when HCC/NT2 folds and was considered to be normal/under-expressed otherwise. HCC patients with PKM2 over-expression had a higher 1-year tumor recurrence rate after surgical resection than HCC patients without PKM2 over-expression, 46.667% Vs 25%. (F) Patients with PKM2 over-expression had lower 5-year overall survival rates after surgical resection. <i>P</i> values were calculated by Kaplan-Meir log rank test.</p