BackgroundMicroRNAs (miRNA) are small non-coding RNAs that regulate translation of mRNA and protein. Loss or enhanced expression of miRNAs is associated with several diseases, including cancer. However, the identification of circulating miRNA in healthy donors is not well characterized. Microvesicles, also known as exosomes or microparticles, circulate in the peripheral blood and can stimulate cellular signaling. In this study, we hypothesized that under normal healthy conditions, microvesicles contain miRNAs, contributing to biological homeostasis.Methodology/Principal FindingsMicrovesicles were isolated from the plasma of normal healthy individuals. RNA was isolated from both the microvesicles and matched mononuclear cells and profiled for 420 known mature miRNAs by real-time PCR. Hierarchical clustering of the data sets indicated significant differences in miRNA expression between peripheral blood mononuclear cells (PBMC) and plasma microvesicles. We observed 71 miRNAs co-expressed between microvesicles and PBMC. Notably, we found 33 and 4 significantly differentially expressed miRNAs in the plasma microvesicles and mononuclear cells, respectively. Prediction of the gene targets and associated biological pathways regulated by the detected miRNAs was performed. The majority of the miRNAs expressed in the microvesicles from the blood were predicted to regulate cellular differentiation of blood cells and metabolic pathways. Interestingly, a select few miRNAs were also predicted to be important modulators of immune function.ConclusionsThis study is the first to identify and define miRNA expression in circulating plasma microvesicles of normal subjects. The data generated from this study provides a basis for future studies to determine the predictive role of peripheral blood miRNA signatures in human disease and will enable the definition of the biological processes regulated by these miRNA.

Context Recent specialty choices of graduating US medical students suggest that lifestyle may be an increasingly important factor in their career decision making. Objective To determine whether and to what degree controllable lifestyle and other specialty-related characteristics are associated with recent (1996-2002) changes in the specialty preferences of US senior medical students. Design and Setting Specialty preference was based on analysis of results from the National Resident Matching Program, the San Francisco Matching Program, and the American Urological Association Matching Program from 1996 to 2002. Specialty lifestyle (controllable vs uncontrollable) was classified using earlier research. Log-linear models were developed that examined specialty preference and the specialty's controllability, income, work hours, and years of graduate medical education required. Main Outcome Measure Proportion of variability in specialty preference from 1996 to 2002 explained by controllable lifestyle. Results The specialty preferences of US senior medical students, as determined by the distribution of applicants across selected specialties, changed significantly from 1996 to 2002 (PϽ.001). In the log-linear model, controllable lifestyle explained 55% of the variability in specialty preference from 1996 to 2002 after controlling for income, work hours, and years of graduate medical education required (PϽ.001). Conclusion Perception of controllable lifestyle accounts for most of the variability in recent changing patterns in the specialty choices of graduating US medical students.

Controllable lifestyle was strongly associated with the recent trends in specialty choice for both women and men and could not be explained solely by the specialty preferences of women.

Therapeutic options for advanced B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) are limited. Available treatments can also deplete T lymphocytes, leaving patients at risk of life-threatening infections. In the National Cancer Institute cell line screen, the structurally unique natural product silvestrol produces an unusual pattern of cytotoxicity that suggests activity in leukemia and selectivity for B cells. We investigated silvestrol efficacy using primary

This is the largest study to date to evaluate the effect of SDB on post-discharge mortality in patients with AHF. Newly diagnosed CSA and OSA during AHF hospitalization are independently associated with post-discharge mortality.