Recommendations of the Blue Ribbon Committee II for the Optimization of Surgical Education and Training in the United States: The Surgical Trainee Perspective.

Objective: This study aims to appraise recommendations from an expert panel of surgical educators on optimizing surgical education and training in the setting of contemporary challenges.

Background: The Blue Ribbon Committee (BRC II), a group of surgical educators, was convened to make recommendations to optimize surgical training, considering the current changes in the landscape of surgical education. Surgical trainees were recruited to assess their impressions of the recommendations.

Glucocorticoid treatment influences prostate cancer cell growth and the tumor microenvironment via altered glucocorticoid receptor signaling in prostate fibroblasts.

Despite significant therapeutic advances in recent years, treatment of metastatic prostate cancer (PCa) remains palliative, owing to the inevitable occurrence of drug resistance. There is increasing evidence that epithelial glucocorticoid receptor (GR) signaling and changes in the tumor-microenvironment (TME) play important roles in this process. Since glucocorticoids (GCs) are used as concomitant medications in the course of PCa treatment, it is essential to investigate the impact of GCs on stromal GR signaling in the TME.

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.

Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.

The power of genetic diversity in genome-wide association studies of lipids.

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels, heart disease remains the leading cause of death worldwide. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease.

Targeting the glucocorticoid receptor signature gene Mono Amine Oxidase-A enhances the efficacy of chemo- and anti-androgen therapy in advanced prostate cancer.

Despite increasing options for treatment of castration-resistant prostate cancer, development of drug resistance is inevitable. The glucocorticoid receptor (GR) is a prime suspect for acquired therapy resistance, as prostate cancer (PCa) cells are able to increase GR signaling during anti-androgen therapy and thereby circumvent androgen receptor (AR)-blockade and cell death. As standard AR-directed therapies fail to block the GR and GR inhibitors might result in intolerable side effects, the identification of GR signature genes, which are better suited for a targeted approach, is of clinical importance.

MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy.

Rationale: The interaction of circulating cells within the vascular wall is a critical event in chronic inflammatory processes, such as atherosclerosis, but the control of the vascular inflammatory state is still largely unclear.

Objective: This study was undertaken to characterize the function of the endothelial-enriched microRNA miR-100 during vascular inflammation and atherogenesis.

Methods And Results: Based on a transcriptome analysis of endothelial cells after miR-100 overexpression, we identified miR-100 as a potent suppressor of endothelial adhesion molecule expression, resulting in attenuated leukocyte-endothelial interaction in vitro and in vivo as shown by flow cytometry and intravital imaging.

The Glucocorticoid Receptor Is a Key Player for Prostate Cancer Cell Survival and a Target for Improved Antiandrogen Therapy.

The major obstacle in the management of advanced prostate cancer is the occurrence of resistance to endocrine therapy. Although the androgen receptor (AR) has been linked to therapy failure, the underlying escape mechanisms have not been fully clarified. Being closely related to the AR, the glucocorticoid receptor (GR) has been suggested to play a role in enzalutamide and docetaxel resistance.

Preclinical Testing of Frequency-Tunable Capacitive Micromachined Ultrasonic Transducer Probe Prototypes.

In intracardiac echocardiography (ICE) it may be beneficial to generate ultrasound images acquired at multiple frequencies, having the possibility of high penetration or high-resolution imaging in a single device. The objective of the presented work is to test two frequency-tunable probe prototypes in a preclinical setting: a rigid probe having a diameter of 11 mm and a new flexible and steerable 12-Fr ICE catheter. Both probes feature a forward-looking 32-element capacitive micromachined ultrasonic transducer array (aperture of 2 × 2 mm) operated in collapse mode, which allows for frequency tuning in the 6-MHz-18-MHz range.

Epithelial-to-mesenchymal transition leads to docetaxel resistance in prostate cancer and is mediated by reduced expression of miR-200c and miR-205.

Docetaxel is a standard chemotherapy for patients with metastatic prostate cancer. However, the response is rather limited and not all of the patients benefit from this treatment. To uncover key mechanisms of docetaxel insensitivity in prostate cancer, we have established docetaxel-resistant sublines.