Co-polymers of Furan with Pyrrole or Thiophene: A Synthetic Study

The use of conductive polymers as a substitute for metallic conductors and semiconductors has attracted much attention in the literature. In particular, aromatic heterocyclic polymers constitute an important class since they possess chemical and electrical stability in both the oxidized (doped) and neutral (undoped) state. Doping a polymer allows one to vary its electrical, mechanical, optical, and thermal properties. The properties of these polymers are promising for their many technological uses such as antistatic coatings, solar cells, and electronic devises. Polyfuran is among the least common heterocyclic polymers. Polyfuran has been reported to be much less stable that either polypyrrole or polythiophene. The preparation of co-polymers of polyfuran with two percent pyrrole or thiophene is reported. The polymers are characterized by *HNMR, IR, and ESR spectroscopy, and the electrical conductivity of the doped and un-doped synthetic polyfuran and co-polymers is provided

Antipsychotic Prescribing Pathways, Polypharmacy, and Clozapine Use in Treatment of Schizophrenia

Objective To ensure optimal care for patients with schizophrenia, antipsychotic medications must be appropriately prescribed and used. Therefore, the primary objectives of this study were to identify and describe pathways for antipsychotic prescribing, assess the consistency of observed pathways with treatment guidelines, and describe variability across facilities. Methods Data from Veterans Affairs administrative data sets from fiscal year (FY) 2003 to FY 2007 were gathered for analysis in this retrospective cohort study of antipsychotic prescribing pathways among 13 facilities across two regional networks. Patients with a new episode of care for schizophrenia or schizoaffective disorder in FY 2005 were identified, and antipsychotic prescribing history was obtained for two years before and after the index diagnosis. Demographic characteristics and distribution of comorbidities were assessed. Median medical center rates of polypharmacy were calculated and compared with Fisher’s exact test. Results Of 1,923 patients with a new episode of schizophrenia care, 1,003 (52%) had complete data on prescribing pathways. A majority (74%) of patients were prescribed antipsychotic monotherapy, and 19% received antipsychotic polypharmacy. Of patients receiving antipsychotic polypharmacy, 65% began polypharmacy within 90 days of starting any antipsychotic treatment. There was a fourfold difference in polypharmacy across facilities. Antipsychotic polypharmacy was not associated with geographic location or medical center patient volume. Clozapine utilization was low (0%–2%). Conclusions Retrospective examination of longitudinal prescribing patterns identified multiple antipsychotic prescribing pathways. Although most patients received guideline-concordant care, antipsychotic polypharmacy was commonly used as initial treatment, and there was substantial variability among facilities. Study findings suggest the utility of secondary data to assess treatment adaptation or switching for practical clinical trials

The transcriptional profile of coronary arteritis in Kawasaki disease

BackgroundKawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. Transcriptome profiling is a powerful approach to investigate gene expression in diseased tissues. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment.MethodsDeep RNA sequencing was performed on KD (n = 8) and childhood control (n = 7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Non-human RNA sequences were subjected to a microbial discovery bioinformatics platform, and microbial sequences were analyzed by Metastats for association with KD.ResultsT lymphocyte activation, antigen presentation, immunoglobulin production, and type I interferon response were significantly upregulated in KD arteritis, while the tumor necrosis factor α pathway was not differentially expressed. Transcripts from known infectious agents were not specifically associated with KD coronary arteritis.ConclusionsThe immune transcriptional profile in KD coronary artery tissues has features of an antiviral immune response such as activated cytotoxic T lymphocyte and type I interferon-induced gene upregulation. These results provide new insights into the pathogenesis of KD arteritis that can guide selection of new immunomodulatory therapies for high-risk KD patients, and provide direction for future etiologic studies

Risk factors for uteroplacental vascular compromise and inflammation

To identify potentially modifiable risk factors of placental injury reflecting maternal uteroplacental vascular compromise (UPVC) and acute and chronic placental inflammation

The metabolome regulates the epigenetic landscape during naive-to-primed human embryonic stem cell transition.

For nearly a century developmental biologists have recognized that cells from embryos can differ in their potential to differentiate into distinct cell types. Recently, it has been recognized that embryonic stem cells derived from both mice and humans exhibit two stable yet epigenetically distinct states of pluripotency: naive and primed. We now show that nicotinamide N-methyltransferase (NNMT) and the metabolic state regulate pluripotency in human embryonic stem cells (hESCs).  Specifically, in naive hESCs, NNMT and its enzymatic product 1-methylnicotinamide are highly upregulated, and NNMT is required for low S-adenosyl methionine (SAM) levels and the H3K27me3 repressive state. NNMT consumes SAM in naive cells, making it unavailable for histone methylation that represses Wnt and activates the HIF pathway in primed hESCs. These data support the hypothesis that the metabolome regulates the epigenetic landscape of the earliest steps in human development

Baker Center Journal of Applied Public Policy, Vol. III No. I

Welcome to the third issue of the Baker Center Journal for Applied PublicPolicy. I am pleased that this issue, as its predecessors, evidences the vibrancy of the Baker Center’s governance and public policy programs and makes a contribution to our collective understanding about a variety of policy issues currently being discussed in America. Relating to our system of governance, Jess Hale Jr. examines a proposal for a uniform state approach to reining in renegade presidential electors and Professor Glenn Reynolds reviews Jack Goldsmith’s book The Terror Presidency: Law and Judgment Inside the Bush Administration. Relating to media and foreign affairs and the role of the media in political life, Dr. Mike Fitzgerald and two of his students provide us with “A Comparative Study of Images Created by Press Coverage of the United States and the Republic of Belarus.” Relating to health policy, Dr. David Mirvis, recently appointed as a Senior Fellow for Health Policy at the Center, explores the public policy implications of viewing health as an engine of economic growth. Relating to energy and environmental policy, Drs. Bruce Tonn and Amy Gibson and Baker Scholars Stephanie Smith and Rachel Tuck explore U.S. Attitudes and Perspectives on National Energy Policy. I am also very pleased that this issue includes a report of an excellent conference – “Formulation of a Bipartisan Energy and Climate Policy: Toward and Open and Transparent Process “- that was co-sponsored by the Baker Center and the Woodrow Wilson International Center for Scholars. This issue also includes the result ofanother successful collaboration between the Baker and Wilson Centers that focused on “Five Public Policy Ideas for Building Obama’s New Economy.” I look forward to further productive collaborations between the Baker and Wilson Centers. Relating to global security policy, this issue includes a Student Symposium onNational Security. Although the Baker Center Journal has provided an outlet for publication of student scholarship since its inception, I am particularly pleased that the student co-editors - Baker Scholars Elizabeth Wilson Vaughan and Bradford A. Vaughan - took the initiative to expand upon the efforts of their predecessors and to provide us with an expanded set of excellent students essays each of which addresses an important national security policy issue. It is an important part of the Baker Center’s mission to engage UTK students in the political and public policy process, and I applaud our student authors fortheir contributions to this symposium. I hope you find this issue of the Baker Center Journal for Applied Public Policy to be both interesting and thought-provoking and that it will encourage you to participate in America’s unique and wonderful political and policy processes

Modulation of the Cellular Expression of Circulating Advanced Glycation End-Product Receptors in Type 2 Diabetic Nephropathy

Background. Advanced glycation end-products (AGEs) and their receptors are prominent contributors to diabetic kidney disease. Methods. Flow cytometry was used to measure the predictive capacity for kidney impairment of the AGE receptors RAGE, AGE-R1, and AGE-R3 on peripheral blood mononuclear cells (PBMCs) in experimental models of type 2 diabetes (T2DM) fed varied AGE containing diets and in obese type 2 diabetic and control human subjects. Results. Diets high in AGE content fed to diabetic mice decreased cell surface RAGE on PBMCs and in type 2 diabetic patients with renal impairment (RI). All diabetic mice had elevated Albumin excretion rates (AERs), and high AGE fed dbdb mice had declining Glomerular filtration rate (GFR). Cell surface AGE-R1 expression was also decreased by high AGE diets and with diabetes in dbdb mice and in humans with RI. PBMC expression of AGE R3 was decreased in diabetic dbdb mice or with a low AGE diet. Conclusions. The most predictive PBMC profile for renal disease associated with T2DM was an increase in the cell surface expression of AGE-R1, in the context of a decrease in membranous RAGE expression in humans, which warrants further investigation as a biomarker for progressive DN in larger patient cohorts

Modeled Health and Economic Impact of Team-Based Care for Hypertension

IntroductionTeam-based interventions for hypertension care have been widely studied and shown effective in improving hypertension outcomes. Few studies have evaluated long-term effects of these interventions; none have assessed broad-scale implementation. This study estimates the prospective health, economic, and budgetary impact of universal adoption of a team-based care intervention model that targets people with treated but uncontrolled hypertension in the U.S.MethodsAnalysis was conducted in 2014−2015 using a microsimulation model, constructed with various data sources from 1948 to 2014, designed to evaluate prospective cardiovascular disease (CVD)−related interventions in the U.S. population. Ten-year primary outcomes included prevalence of uncontrolled hypertension; incident myocardial infarction, stroke, CVD events, and CVD-related mortality; intervention and net medical costs by payer; productivity; and quality-adjusted life years.ResultsAbout 4.7 million (13%) fewer people with uncontrolled hypertension and 638,000 prevented cardiovascular events would be expected over 10 years. Assuming $525 per enrollee, implementation would cost payers$22.9 billion, but $25.3 billion would be saved in averted medical costs. Estimated net cost savings for Medicare approached$5.8 billion. Net costs were especially sensitive to intervention costs, with break-even thresholds of $300 (private),$450 (Medicaid), and $750 (Medicare).ConclusionsNationwide adoption of team-based care for uncontrolled hypertension could have sizable effects in reducing CVD burden. Based on the study’s assumptions, the policy would be cost saving from the perspective of Medicare and may prove to be cost effective from other payers’ perspectives. Expected net cost savings for Medicare would more than offset expected net costs for all other insurers

Recommendations for selecting drug-drug interactions for clinical decision support

To recommend principles for including drug-drug interactions (DDIs) in clinical decision support