Screening of microRNAs controlling body fat in Drosophila melanogaster and identification of miR-969 and its target, Gr47b.

MicroRNAs (miRNAs) are small non-protein coding RNAs and post-transcriptionally regulate cellular gene expression. In animal development, miRNAs play essential roles such as stem cell maintenance, organogenesis, and apoptosis. Using gain-of-function (GOF) screening with 160 miRNA lines in Drosophila melanogaster, we identified a set of miRNAs which regulates body fat contents and named them microCATs (microRNAs Controlling Adipose Tissue). Further examination of egg-to-adult developmental kinetics of selected miRNA lines showed a negative correlation between fat content and developmental time. Comparison of microCATs with loss-of-function miRNA screening data uncovered miR-969 as an essential regulator of adiposity. Subsequently, we demonstrated adipose tissue-specific knock-down of gustatory receptor 47b (Gr47b), a miR-969 target, greatly reduced the amount of body fat, recapitulating the miR-969 GOF phenotype.

Cluster-Randomized Trial of Clinical Pharmacist Tobacco Cessation Counseling Among Patients with Cardiovascular Disease.

Optimal management of patients with cardiovascular disease (CVD) includes evaluation of risk factors using a team-based approach. Tobacco use often receives less attention than other CVD risk factors; therefore, utilization of nonphysician health care providers may be valuable in addressing tobacco use. The purpose of this trial was to assess the impact of brief, structured, telephone tobacco cessation counseling (BST) delivered by clinical pharmacists on tobacco cessation attempts compared to usual care. The BST consisted of 1 to 5 minutes discussing 3 key counseling points, including a recommendation to quit and education about cessation aids. This was a cluster-randomized trial of tobacco-using patients with CVD who were enrolled in a clinical pharmacist-managed, physician-directed, CVD disease state management service. Clinical pharmacists were randomized to provide usual care (control) or BST (intervention) to their tobacco-using patients during a 4-month period. Patients were surveyed 3 months later to assess their tobacco cessation attempts, use of tobacco cessation aids, and self-reported cessation. One hundred twenty patients were enrolled. Subjects were predominately white males, aged ≥65 years, with a history of myocardial infarction. One hundred and four subjects completed the follow-up survey. No differences were detected between the 36.2% and 38.6% of control and intervention subjects, respectively, reporting a tobacco cessation attempt (P=0.804) or in the other outcomes (all P>0.05). A BST delivered by clinical pharmacists may not adequately affect patient motivation enough to increase tobacco cessation attempts in tobacco-dependent patients with CVD. Future research is needed to evaluate other team-based strategies that can decrease tobacco use in patients with CVD.

Attainment of low-density lipoprotein cholesterol goals in coronary artery disease.

BACKGROUND: The National Cholesterol Education Program Guidelines offer an optional low-density lipoprotein cholesterol (LDL-C) goal of less than 70 mg/dL for very high-risk patients with coronary artery disease (CAD). This study evaluated the extent to which this recommendation can be attained by the use of currently available lipid-lowering therapies. METHODS: A retrospective, cross-sectional study of patients in the Kaiser Permanente Colorado healthcare system 18 years of age or older with CAD and a predetermined LDL-C goal less than 70 mg/dL. The LDL-C most proximal, but within 1 year before April 1, 2008, was deemed the qualifying LDL-C and used to determine LDL-C goal attainment. Lipid-lowering medication(s) for those attaining goal and factors associated with failure to attain LDL-C goal also were identified. RESULTS: A total of 7427 patients were included in the study. A total of 3226 patients attained a LDL-C less than 70 mg/dL. The majority (92.4%) attaining goal were receiving statin monotherapy or in combination compared with 81.3% not at goal (P < .001). More than one-half attained goal on statin monotherapy with 70.7% at moderate- to high-potency doses and 87.4% on generically available statin. Nearly one-third attaining goal received statin in combination. Ezetimibe (70.6%) was most frequently used with statin. Factors independently associated with failure to attain a LDL-C less than 70 mg/dL were age younger than 65 years, patients not receiving statin, a history of creatine kinase elevation, and female sex. CONCLUSION: This study reports the greatest rate of LDL-C less than 70 mg/dL goal attainment in a very high-risk population with CAD to date. However, despite a system dedicated to aggressively treat to a LDL-C goal of less than 70 mg/dL, success in the majority is a challenge with the currently available therapies.