Category: Uncategorized

Hot Topics: Peer-Reviewed Blog Introduces New Medical Researchers to Publishing

Coached Peer Review: Developing the Next Generation of Authors

Sidalak D, Purdy E, Luckett-Gatopoulos S, Murray H, Thoma B, Chan TM. Coached peer review: Developing the next generation of authors. Academic Medicine. 2017;92(2):201-204. http://dx.doi.org/10.1097/ACM.0000000000001224.

Problem
Publishing in academic journals is challenging for learners. Those who pass the initial stages of internal review by an editor often find the anonymous peer review process harsh. Academic blogs offer alternate avenues for publishing medical education material. Many blogs, however, lack a peer review process, which some consumers argue compromises the quality of materials published.

Approach
CanadiEM (formerly BoringEM) is an academic educational emergency medicine blog dedicated to publishing high-quality materials produced by learners (i.e., residents and medical students). The editorial team has designed and implemented a collaborative “coached peer review” process that comprises an open exchange among the learner–author, editors, and reviewers. The goal of this process is to facilitate the publication of high-quality academic materials by learner–authors while providing focused feedback to help them develop academic writing skills.

Outcomes
The authors of this Innovation Report surveyed (February–June 2015) their blog’s learner–authors and external expert “staff” reviewers who had participated in coached peer review for their reactions to the process. The survey results revealed that participants viewed the process positively compared with both traditional journal peer review and academic blog publication processes. Participants found the process friendly, easy, efficient, and transparent. Learner–authors also reported increased confidence in their published material. These outcomes met the goals of coached peer review.

Next Steps
CanadiEM aims to inspire continued participation in, exposure to, and high quality production of academic writing by promoting the adoption of coached peer review for online educational resources produced by learners.

Posted in Front Page, Hot Topics in Research, Research Commentary, Uncategorized

Prostate cancer discovery may make it easier to kill cancer cells

Checkpoint Kinase 2 Negatively Regulates Androgen Sensitivity and Prostate Cancer Cell Growth

Abstract:

Prostate cancer is the second leading cause of cancer death in American men, and curing metastatic disease remains a significant challenge. Nearly all patients with disseminated prostate cancer initially respond to androgen deprivation therapy (ADT), but virtually all patients will relapse and develop incurable castrationresistant prostate cancer (CRPC). A high-throughput RNAi screen to identify signaling pathways regulating prostate cancer cell growth led to our discovery that checkpoint kinase 2 (CHK2) knockdown dramatically increased prostate cancer growth and hypersensitized cells to low androgen levels. Mechanistic investigations revealed that the effects of CHK2 were dependent on the downstream signaling proteins CDC25C and CDK1. Moreover, CHK2depletion increased androgen receptor (AR) transcriptional activity on androgen-regulated genes, substantiating the finding that CHK2 affects prostate cancer proliferation, partly, through the AR. Remarkably, we further show that CHK2 is a novel ARrepressed gene, suggestive of a negative feedback loop between CHK2 and AR. In addition, we provide evidence that CHK2 physically associates with the AR and that cell-cycle inhibition increased this association. Finally, IHC analysis of CHK2 in prostate cancer patient samples demonstrated a decrease in CHK2 expression in high-grade tumors. In conclusion, we propose that CHK2 is a negative regulator of androgen sensitivity and prostate cancer growth, and that CHK2 signaling is lost during prostate cancer progression to castration resistance. Thus, perturbing CHK2 signaling may offer a new therapeutic approach for sensitizing CRPC to ADT and radiation.

 

Cancer Research. 12/1/2015, Vol. 75 Issue 23, p5093-5105. 13p.

Posted in Hot Topics in Research, Oncology, Prostate, Uncategorized

Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis

Non-lethal Inhibition of Gut

Abstract:

Trimethylamine (TMA) N-oxide (TMAO), a gut-microbiota-dependent metabolite, both enhances atherosclerosis in animal models and is associated with cardiovascular risks in clinical studies. Here, we investigate the impact of targeted inhibition of the first step in TMAO generation, commensal microbial TMA production, on diet-induced atherosclerosis. A structural analog of choline, 3,3-dimethyl-1-butanol (DMB), is shown to non-lethally inhibit TMA formation from cultured microbes, to inhibit distinct microbial TMA lyases, and to both inhibit TMA production from physiologic polymicrobial cultures (e.g., intestinal contents, human feces) and reduce TMAO levels in mice fed a high-choline or L-carnitine diet. DMB inhibited choline diet-enhanced endogenous macrophage foam cell formation and atherosclerotic lesion development in apolipoprotein e−/− mice without alterations in circulating cholesterol levels. The present studies suggest that targeting gut microbial production of TMA specifically and non-lethal microbial inhibitors in general may serve as a potential therapeutic approach for the treatment of cardiometabolic diseases. •Gut microbial trimethylamine lyases are a therapeutic target for atherosclerosis•3,3-dimethyl-1-butanol inhibits microbial trimethylamine formation•3,3-dimethyl-1-butanol attenuates choline diet-enhanced atherosclerosis•Non-lethal gut microbial enzyme inhibition can impact host cardiometabolic phenotypes Drugging the gut microbiota with a non-lethal inhibitor that blocks production of the metabolite trimethylamine reduces the formation of atherosclerotic lesions and represents the first step toward treatment of cardiometabolic diseases by targeting the microbiome.

Cell 17 December 2015 163(7):1585-1595

Posted in Cardiology, Hot Topics in Research, Uncategorized