Long Noncoding RNA-Directed Epigenetic Regulation of Gene Expression Is Associated With Anxiety-like Behavior in Mice

Background RNA-directed regulation of epigenetic processes has recently emerged as an important feature of mammalian differentiation and development. Perturbation of this regulatory system in the brain may contribute to the development of neuropsychiatric disorders. Methods RNA sequencing was used to identify changes in the experience-dependent expression of long noncoding RNAs (lncRNAs) within the medial prefrontal cortex of adult mice. Transcripts were validated by real-time quantitative polymerase chain reaction and a candidate lncRNA, Gomafu, was selected for further investigation. The functional role of this schizophrenia-related lncRNA was explored in vivo by antisense oligonucleotide-mediated gene knockdown in the medial prefrontal cortex, followed by behavioral training and assessment of fear-related anxiety. Long noncoding RNA-directed epigenetic regulation of gene expression was investigated by chromatin and RNA immunoprecipitation assays. Results RNA sequencing analysis revealed changes in the expression of a significant number of genes related to neural plasticity and stress, as well as the dynamic regulation of lncRNAs. In particular, we detected a significant downregulation of Gomafu lncRNA. Our results revealed that Gomafu plays a role in mediating anxiety-like behavior and suggest that this may occur through an interaction with a key member of the polycomb repressive complex 1, BMI1, which regulates the expression of the schizophrenia-related gene beta crystallin (Crybb1). We also demonstrated a novel role for Crybb1 in mediating fear-induced anxiety-like behavior. Conclusions Experience-dependent expression of lncRNAs plays an important role in the epigenetic regulation of adaptive behavior, and the perturbation of Gomafu may be related to anxiety and the development of neuropsychiatric disorders

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Survey on the use of premix insulin analogues in diabetes mellitus type 1 and 2 in Mexico [Encuesta sobre el uso de premezclas de an�logos de insulinas en pacientes con diabetes en M�xico]

Background: There are several publications related to the use of premixed insulin analogs in Type 1 and 2 Diabetes Mellitus, however, there was no information about its use in the Mexican clinical practice. Materials and methods: A survey was conducted to 48 physicians experts in Diabetes Mellitus. They were endocrinologists (62%), Internists (32) and diabetologists (6%). Results: Twenty-four percent of the specialists pointed out that more than half of the patients who consult by the first time do not respond to treatment with oral hypoglycemic medication. A high number of patients treated with insulin reach glycemic control goals. Most of the experts treat more than half of their patients with insulin. Sixty-six percent of the experts use premixed insulin analogs in their patients with type 1 Diabetes, and a high percentage use them in type 2 Diabetes. Most of the expert physicians recommend the use of premixed insulin analogs as the first line treatment in their patients diagnosed with Type 2 Diabetes. Conclusions: Premixed insulin analogs are widely accepted by patients because they offer a complete coverage of their metabolic requirements, reducing the number of daily injections. In type 1 Diabetes, premixed insulin analogs will be used to improve metabolic control and to strengthen compliance. This document describes the use of premixed insulin analogs in the treatment of Diabetes Mellitus in Mexico

Survey on the use of premix insulin analogues in diabetes mellitus type 1 and 2 in Mexico [Encuesta sobre el uso de premezclas de análogos de insulinas en pacientes con diabetes en México]

Background: There are several publications related to the use of premixed insulin analogs in Type 1 and 2 Diabetes Mellitus, however, there was no information about its use in the Mexican clinical practice. Materials and methods: A survey was conducted to 48 physicians experts in Diabetes Mellitus. They were endocrinologists (62%), Internists (32) and diabetologists (6%). Results: Twenty-four percent of the specialists pointed out that more than half of the patients who consult by the first time do not respond to treatment with oral hypoglycemic medication. A high number of patients treated with insulin reach glycemic control goals. Most of the experts treat more than half of their patients with insulin. Sixty-six percent of the experts use premixed insulin analogs in their patients with type 1 Diabetes, and a high percentage use them in type 2 Diabetes. Most of the expert physicians recommend the use of premixed insulin analogs as the first line treatment in their patients diagnosed with Type 2 Diabetes. Conclusions: Premixed insulin analogs are widely accepted by patients because they offer a complete coverage of their metabolic requirements, reducing the number of daily injections. In type 1 Diabetes, premixed insulin analogs will be used to improve metabolic control and to strengthen compliance. This document describes the use of premixed insulin analogs in the treatment of Diabetes Mellitus in Mexico