Pigment analysis by Raman microscopy and portable X-ray fluorescence (pXRF) of thirteenth to fourteenth century illuminations and cuttings from Bologna

Non-destructive pigment analysis by Raman microscopy (RM) and portable X-ray fluorescence (pXRF) has been carried out on some Bolognese illuminations and cuttings chosen to represent the beginnings, evolution and height of Bolognese illuminated manuscript production. Dating to the thirteenth and fourteenth centuries and held in a private collection, the study provides evidence for the pigments generally used in this period. The results, which are compared with those obtained for other north Italian artwork, show the developments in usage of artistic materials and technique. Also addressed in this study is an examination of the respective roles of RM and pXRF analysis in this area of technical art history

Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice

Previous research has shown that mifepristone can prevent and reverse weight gain in animals and human subjects taking antipsychotic medications. This proof-of-concept study tested whether a more potent and selective glucocorticoid receptor antagonist could block dietary-induced weight gain and increase insulin sensitivity in mice. Ten-week-old, male, C57BL/6J mice were fed a diet containing 60% fat calories and water supplemented with 11% sucrose for 4 weeks. Groups (n = 8) received one of the following: CORT 108297 (80 mg/kg QD), CORT 108297 (40 mg/kg BID), mifepristone (30 mg/kg BID), rosiglitazone (10 mg/kg QD), or vehicle. Compared to mice receiving a high-fat, high-sugar diet plus vehicle, mice receiving a high-fat, high-sugar diet plus either mifepristone or CORT 108297 gained significantly less weight. At the end of the four week treatment period, mice receiving CORT 108297 40 mg/kg BID or CORT 108297 80 mg/kg QD also had significantly lower steady plasma glucose than mice receiving vehicle. However, steady state plasma glucose after treatment was not highly correlated with reduced weight gain, suggesting that the effect of the glucocorticoid receptor antagonist on insulin sensitivity may be independent of its mitigating effect on weight gain

Disparities in routine breast cancer screening for medicaid managed care members with a work-limiting disability

Objective: Examine disparities in routine mammography for women who qualify for Medicaid, because of a work-limiting disability. Methods: Individual-level data were obtained for women enrolled in Massachusetts Medicaid Managed Care plans who met the 2007 Healthcare Effectiveness Data and Information Set (HEDIS) criteria for the breast cancer screening measure (n=35,171). Disability status was determined from Medicaid eligibility records. Mammography screening was modeled using multivariate logistic regression. Separate models for women with and without a disability were also estimated. Results: Although unadjusted breast cancer screening rates were roughly equal for women with and without disability, after adjusting for confounders disability status had a significant negative association with screening mammography (OR=0.74; p Conclusion: Nationwide, rates of routine mammography for Medicaid managed care plans averaged below 50% in 2006. Given that a majority of eligible women served by Medicaid have disabilities, and studies have shown that women with disabilities are more likely to be diagnosed with late stage disease, a focus on improving rates of screening for women with disabilities is overdue

The Impact of Prior Authorization on Buprenorphine Dose, Relapse and Cost of Opioid Addiction Treatment

This presentation discusses the impact of prior authorization on Buprenorphine dose, relapse, and cost for opioid addiction treatment for Massachusetts Medicaid members. Presented at the AcademyHealth Annual Research Meeting 2013

Limiting the Duration of Medication Assisted Treatment for Opioid Addiction: Will New State Policies Help or Hurt?

This presentation details the impact of state Medicaid programs placing lifetime limits on buprenorphine therapy for individuals with opioid dependence. The research reveals that setting limits does not save money or help the patient

Advanced glycation end products:An emerging biomarker for adverse outcome in patients with peripheral artery disease

AbstractPatients with peripheral artery disease (PAD) suffer from widespread atherosclerosis. Partly due to the growing awareness of cardiovascular disease, the incidence of PAD has increased considerably during the past decade. It is anticipated that algorithms to identify high risk patients for cardiovascular events require being updated, making use of novel biomarkers. Advanced glycation end products (AGEs) are moieties formed non-enzymatically on long-lived proteins under influence of glycemic and oxidative stress reactions. We elaborate about the formation and effects of AGEs, and the methods to measure AGEs. Several studies have been performed with AGEs in PAD. In this review, we evaluate the emerging evidence of AGEs as a clinical biomarker for patients with PAD

T-cell production of matrix metalloproteinases and inhibition of parasite clearance by TIMP-1 during chronic Toxoplasma infection in the brain

Chronic infection with the intracellular protozoan parasite Toxoplasma gondii leads to tissue remodelling in the brain and a continuous requirement for peripheral leucocyte migration within the CNS (central nervous system). In the present study, we investigate the role of MMPs (matrix metalloproteinases) and their inhibitors in T-cell migration into the infected brain. Increased expression of two key molecules, MMP-8 and MMP-10, along with their inhibitor, TIMP-1 (tissue inhibitor of metalloproteinases-1), was observed in the CNS following infection. Analysis of infiltrating lymphocytes demonstrated MMP-8 and -10 production by CD4+ and CD8+ T-cells. In addition, infiltrating T-cells and CNS resident astrocytes increased their expression of TIMP-1 following infection. TIMP-1-deficient mice had a decrease in perivascular accumulation of lymphocyte populations, yet an increase in the proportion of CD4+ T-cells that had trafficked into the CNS. This was accompanied by a reduction in parasite burden in the brain. Taken together, these findings demonstrate a role for MMPs and TIMP-1 in the trafficking of lymphocytes into the CNS during chronic infection in the brain

Results of ASERTAA, a randomized prospective crossover pharmacogenetic study of immediate-release versus extended-release tacrolimus in African American kidney transplant recipients

BACKGROUND: Differences in tacrolimus dosing across ancestries is partly attributable to polymorphisms in CYP3A5 genes that encode tacrolimus-metabolizing cytochrome P450 3A5 enzymes. The CYP3A5*1 allele, preponderant in African Americans, is associated with rapid metabolism, subtherapeutic concentrations, and higher dose requirements for tacrolimus, all contributing to worse outcomes. Little is known about the relationship between CYP3A5 genotype and the tacrolimus pharmacokinetic area under the curve (AUC) profile in African Americans or whether pharmacogenetic differences exist between conventional twice-daily, rapidly absorbed, immediate-release tacrolimus (IR-Tac) and once-daily extended-release tacrolimus (LifeCycle Pharma Tac [LCPT]) with a delayed absorption profile. STUDY DESIGN: Randomized prospective crossover study. SETTING & PARTICIPANTS: 50 African American maintenance kidney recipients on stable IR-Tac dosing. INTERVENTION: Recipients were randomly assigned to continue IR-Tac on days 1 to 7 and then switch to LCPT on day 8 or receive LCPT on days 1 to 7 and then switch to IR-Tac on day 8. The LCPT dose was 85% of the IR-Tac total daily dose. OUTCOMES: Tacrolimus 24-hour AUC (AUC MEASUREMENTS: CYP3A5 genotype, 24-hour tacrolimus pharmacokinetic profiles. RESULTS: ∼80% of participants carried the CYP3A5*1 allele (CYP3A5 expressers). There were no significant differences in AUC LIMITATIONS: This was primarily a pharmacogenetic study rather than an efficacy study; the follow-up period was too short to capture clinical outcomes. CONCLUSIONS: Achieving therapeutic tacrolimus trough concentrations with IR-Tac in most African Americans results in significantly higher peak concentrations, potentially magnifying the risk for toxicity and adverse outcomes. This pharmacogenetic effect is attenuated by delayed tacrolimus absorption with LCPT. TRIAL REGISTRATION: Registered at ClinicalTrials.gov, with study number NCT01962922

Simulations of the Milky Way's central molecular zone -- I. Gas dynamics

We use hydrodynamical simulations to study the Milky Way's central molecular zone (CMZ). The simulations include a non-equilibrium chemical network, the gas self-gravity, star formation and supernova feedback. We resolve the structure of the interstellar medium at sub-parsec resolution while also capturing the interaction between the CMZ and the bar-driven large-scale flow out to R\sim 5\kpc. Our main findings are as follows: (1) The distinction between inner ($R\lesssim120$~pc) and outer ($120\lesssim R\lesssim450$~pc) CMZ that is sometimes proposed in the literature is unnecessary. Instead, the CMZ is best described as single structure, namely a star-forming ring with outer radius $R\simeq 200$~pc which includes the 1.3$^\circ$ complex and which is directly interacting with the dust lanes that mediate the bar-driven inflow. (2) This accretion can induce a significant tilt of the CMZ out of the plane. A tilted CMZ might provide an alternative explanation to the $\infty$-shaped structure identified in Herschel data by Molinari et al. 2011. (3) The bar in our simulation efficiently drives an inflow from the Galactic disc ($R\simeq 3$~kpc) down to the CMZ ($R\simeq200$~pc) of the order of $1\rm\,M_\odot\,yr^{-1}$, consistent with observational determinations. (4) Supernova feedback can drive an inflow from the CMZ inwards towards the circumnuclear disc of the order of $\sim0.03\,\rm M_\odot\,yr^{-1}$. (5) We give a new interpretation for the 3D placement of the 20 and 50 km s$^{-1}$ clouds, according to which they are close ($R\lesssim30$~pc) to the Galactic centre, but are also connected to the larger-scale streams at $R\gtrsim100$~pc.Comment: Accepted for publication in MNRAS. Movies of the simulations can be found at: https://www.youtube.com/channel/UCwnzfO-xLxzRDz9XsexfPo

The inositol-3-phosphate synthase biosynthetic enzyme has distinct catalytic and metabolic roles

Inositol levels, maintained by the biosynthetic enzyme inositol-3-phosphate synthase (Ino1), are altered in a range of disorders including bipolar disorder and Alzheimer's disease. To date, most inositol studies have focused on the molecular and cellular effects of inositol depletion without considering Ino1 levels. Here we employ a simple eukaryote, Dictyostelium, to demonstrate distinct effects of loss of Ino1 and inositol depletion. We show that loss of Ino1 results in inositol auxotrophy that can only be partially rescued by exogenous inositol. Removal of inositol supplementation from the ino1- mutant results in a rapid 56% reduction in inositol levels, triggering the induction of autophagy, reduced cytokinesis and substrate adhesion. Inositol depletion also caused a dramatic generalised decrease in phosphoinositide levels that was rescued by inositol supplementation. However, loss of Ino1 triggered broad metabolic changes consistent with the induction of a catabolic state that was not rescued by inositol supplementation. These data suggest a metabolic role for Ino1 independent of inositol biosynthesis. To characterise this role, an Ino1 binding partner containing SEL1L1 domains (Q54IX5) was identified with homology to mammalian macromolecular complex adaptor proteins. Our findings therefore identify a new role for Ino1, independent of inositol biosynthesis, with broad effects on cell metabolism