Implications of New Cholesterol Treatment Guidelines on Statin Utilization, Intensity, and Costs in Active Duty Service Members.

Background: The recommendations in the 2013 American College of Cardiology/American Heart Association (ACC/AHA) blood cholesterol guidelines expanded the indications and level of intensity of statin therapy for the primary prevention of cardiovascular disease. We assessed the treatment and cost implications of theseguidelines within a cohort of active duty service members. Methods: Using the military electronic medical record system, the Armed Forces Health Longitudinal Technology Application, we randomly selected 1,000 active duty persons aged 40 yr or older and reviewed their lipid profiles and medical records to identify risk factors for atherosclerotic cardiovascular disease. We compared the recommended cholesterol treatment under the new ACC/AHA guidelines versus the Third Adult Treatment Panel of the National Cholesterol Education Program. Findings: The mean age was 49 ± 7 yr, 36% were female, 22% were on baseline statin therapy (4% high intensity), and 13% were not at Third Adult Treatment Panel cholesterol goal. There was no difference in the proportion eligible for statin therapy between ACC/AHA and Third Adult Treatment Panel guidelines. Statin treatment under the ACC/AHA guideline resulted in a mean statin dose increase from 25 ± 20 mg to 36 ± 25 mg (p < 0.001) with an increase in those eligible for high-intensity statin therapy, 6% to 11% (p < 0.001). These changes translated to higher estimated yearly statin acquisition costs, $40,197 versus $52,527 per 1,000 patient-years of treatment (p < 0.001). Discussion: Within a low-risk active duty population over 40 yr, application of the 2013 ACC/AHA cholesterol treatment guidelines may not significantly increase those eligible for statins, but may increase statin treatment intensity and costs.

A visual screen of protein localization during sporulation identifies new components of prospore membrane-associated complexes in budding yeast.

During ascospore formation in Saccharomyces cerevisiae, the secretory pathway is reorganized to create new intracellular compartments, termed prospore membranes. Prospore membranes engulf the nuclei produced by the meiotic divisions, giving rise to individual spores. The shape and growth of prospore membranes are constrained by cytoskeletal structures, such as septin proteins, that associate with the membranes. Green fluorescent protein (GFP) fusions to various proteins that associate with septins at the bud neck during vegetative growth as well as to proteins encoded by genes that are transcriptionally induced during sporulation were examined for their cellular localization during prospore membrane growth. We report localizations for over 100 different GFP fusions, including over 30 proteins localized to the prospore membrane compartment. In particular, the screen identified IRC10 as a new component of the leading-edge protein complex (LEP), a ring structure localized to the lip of the prospore membrane. Localization of Irc10 to the leading edge is dependent on SSP1, but not ADY3. Loss of IRC10 caused no obvious phenotype, but an ady3 irc10 mutant was completely defective in sporulation and displayed prospore membrane morphologies similar to those of an ssp1 strain. These results reveal the architecture of the LEP and provide insight into the evolution of this membrane-organizing complex.

Ritualistic chewing behavior induced by mCPP in the rat is an animal model of obsessive compulsive disorder.

Obsessive Compulsive Disorder (OCD) is characterized by recurrent, anxiety-producing thoughts accompanied by unwanted, overwhelming urges to perform ritualistic behaviors. Pharmacological treatments for this disorder (serotonin uptake inhibitors) are problematic because there is a 6-8 week delayed onset and half of the patients do not adequately respond. The present study evaluated whether Ritualistic Chewing Behaviors (RCBs) induced by the serotonin agonist mCPP in the rat is a behavioral model for OCD. The effects upon the RCBs induced by mCPP (1 mg/kg) were evaluated following treatments with either the serotonin antagonist mianserin (3 mg/kg), the dopamine antagonist haloperidol (1 mg/kg), the GABA modulator diazepam (10 mg/kg), or the serotonin uptake inhibitors clomipramine and fluvoxamine (15 mg/kg). The response to mCPP was blocked by acute treatment with mianserin, but not with acute haloperidol or diazepam. Further experiments revealed that the effects of mCPP were blocked by chronic, but not acute, treatment with clomipramine and fluvoxamine. A time-course demonstrated that 14 days of chronic treatment were required for blockade of the mCPP-evoked response. The current study demonstrates that mCPP-evoked RCBs may be a rodent model for OCD that can be used to predict the clinical efficacy and time course of novel OCD treatment. Future investigations may be able to use the current model as a tool for bench-marking corresponding changes in other measures of neurological activity that may provide insight into the mechanisms underlying OCD.