Treatment of Homozygous Familial Hypercholesterolemia: Challenges and Latest Development

Familial hypercholesterolemia (FH) is an autosomal codominant genetic disorder of lipoprotein metabolism. Patients can be heterozygous (HeFH) with one mutated allele, homozygous (HoFH) with two identical mutations, or compound heterozygous with different mutations in each allele. HoFH is the more severe form of the disease and is associated with extremely elevated levels of total cholesterol and low‐density lipoprotein cholesterol (LDL‐C). These lipid abnormalities are associated with accelerated atherosclerosis and cardiovascular disease (CVD) and an increased risk of cardiac events and early death. The prevalence of HoFH has been estimated to be 1 in 1 million; however, this is likely an underestimation as the disease is substantially underdiagnosed and undertreated. Early diagnosis and treatment are important to reduce CVD events. Aggressive therapy with conventional agents such as statins and ezetimibe produce substantial reductions in LDL‐C, but patients rarely reach target goals. Apheresis should be considered in all patients with HoFH, although LDL‐C levels rapidly rebound to baseline levels. Three recently introduced novel agents (mipomersen, lomitapide, and evolocumab)—each with a unique mechanism of action—have increased therapeutic options in this difficult‐to‐treat population. When added to standard therapy, these agents produce significant additional LDL‐C lowering and can potentially improve clinical outcomes

Managing Early Adoption of Biodiesel by Commercial Fleets

Commercial carriers are being confronted with a variety of decisions regarding long-term petroleum dependency and near-term state and federal policies aimed at increasing the use and content of biodiesel. The purpose of this study is to help members of the Iowa Motor Truck Association identify problems regarding the use of biodiesel blends in trucks. The participating trucking company provided two trucks that ran on similar routes, one truck using regular diesel fuel (B0) and the other one using a 2% biodiesel blend (B2). Complete mileage data and special maintenance concerns were recorded over a period of approximately one year. Iowa State University researchers analyzed and interpreted the field data in terms of fuel economy, variations in maintenance, and seasonal performance. Data acquired from July 2006 through May 2007 were analyzed. Special attention was paid to the concern of fuel filter plugging resulting from using B2. During the period of this study, the B0 truck accumulated approximately 160,000 miles and the B2 truck accumulated about 120,000 miles. Field results indicate that both fuels provided similar miles per gallon numbers, even for different trip lengths. The average miles per gallon were 6.0 for the B0 truck and 6.1 for the B2 truck. Overall, the fuel economies of the two engines using B0 and B2 were very similar. In addition, no fuel filter plugging incidents in the B2 truck were found, even during the winter months. The final data are encouraging in terms of using B2 as an alternative fuel for trucks

Some Like It Hot, Some Like It Warm: Phenotyping To Explore Thermotolerance Diversity

Plants have evolved overlapping but distinct cellular responses to different aspects of high temperature stress. These responses include basal thermotolerance, short- and long-term acquired thermotolerance, and thermotolerance to moderately high temperatures. This ‘thermotolerance diversity’ means that multiple phenotypic assays are essential for fully describing the functions of genes involved in heat stress responses. A large number of genes with potential roles in heat stress responses have been identified using genetic screens and genome wide expression studies. We examine the range of phenotypic assays that have been used to characterize thermotolerance phenotypes in both Arabidopsis and crop plants. Three major variables differentiate thermotolerance assays: (1) the heat stress regime used, (2) the developmental stage of the plants being studied, and (3) the actual phenotype which is scored. Consideration of these variables will be essential for deepening our understanding of the molecular genetics of plant thermotolerance