Theories and Empirical Studies of International Institutions

Governmen

DNA methylation at the mu-1 opioid receptor gene (OPRM1) promoter predicts preoperative, acute, and chronic postsurgical pain after spine fusion.

INTRODUCTION:The perioperative pain experience shows great interindividual variability and is difficult to predict. The mu-1 opioid receptor gene (OPRM1) is known to play an important role in opioid-pain pathways. Since deoxyribonucleic acid (DNA) methylation is a potent repressor of gene expression, DNA methylation was evaluated at the OPRM1 promoter, as a predictor of preoperative, acute, and chronic postsurgical pain (CPSP). METHODS:A prospective observational cohort study was conducted in 133 adolescents with idiopathic scoliosis undergoing spine fusion under standard protocols. Data regarding pain, opioid consumption, anxiety, and catastrophizing (using validated questionnaires) were collected before and 2-3 months postsurgery. Outcomes evaluated were preoperative pain, acute postoperative pain (area under curve [AUC] for pain scores over 48 hours), and CPSP (numerical rating scale >3/10 at 2-3 months postsurgery). Blood samples collected preoperatively were analyzed for DNA methylation by pyrosequencing of 22 CpG sites at the OPRM1 gene promoter. The association of each pain outcome with the methylation percentage of each CpG site was assessed using multivariable regression, adjusting for significant (P<0.05) nongenetic variables. RESULTS:Majority (83%) of the patients reported no pain preoperatively, while CPSP occurred in 36% of the subjects (44/121). Regression on dichotomized preoperative pain outcome showed association with methylation at six CpG sites (1, 3, 4, 9, 11, and 17) (P<0.05). Methylation at CpG sites 4, 17, and 18 was associated with higher AUC after adjusting for opioid consumption and preoperative pain score (P<0.05). After adjusting for postoperative opioid consumption and preoperative pain score, methylation at CpG sites 13 and 22 was associated with CPSP (P<0.05). DISCUSSION:Novel CPSP biomarkers were identified in an active regulatory region of the OPRM1 gene that binds multiple transcription factors. Inhibition of binding by DNA methylation potentially decreases the OPRM1 gene expression, leading to a decreased response to endogenous and exogenous opioids, and an increased pain experience

The MAPPINGS III Library of Fast Radiative Shock Models

We present a new library of fully-radiative shock models calculated with the MAPPINGS III shock and photoionization code. The library consists of grids of models with shock velocities in the range v=100-1000 km/s and magnetic parameters B/sqrt(n) of 10^-4 - 10 muG cm^(3/2) for five different atomic abundance sets, and for a pre-shock density of 1.0 cm^(-3). Additionally, Solar abundance model grids have been calculated for densities of 0.01, 0.1, 10, 100, and 1000 cm^(-3) with the same range in v and B/sqrt(n). Each model includes components of both the radiative shock and its photoionized precursor, ionized by the EUV and soft X-ray radiation generated in the radiative gas. We present the details of the ionization structure, the column densities, and the luminosities of the shock and its precursor. Emission line ratio predictions are separately given for the shock and its precursor as well as for the composite shock+precursor structure to facilitate comparison with observations in cases where the shock and its precursor are not resolved. Emission line ratio grids for shock and shock+precursor are presented on standard line ratio diagnostic diagrams, and we compare these grids to observations of radio galaxies and a sample of AGN and star forming galaxies from the Sloan Digital Sky Survey. This library is available online, along with a suite of tools to enable the analysis of the shocks and the easy creation of emission line ratio diagnostic diagrams. These models represent a significant increase in parameter space coverage over previously available models, and therefore provide a unique tool in the diagnosis of emission by shocks.Comment: 39 pages, 34 figures, accepted for publication in ApJS, April 200

Making Women\u27s Health Connections: Between Researchers and to Resources

The Lamar Soutter Library at the University of Massachusetts Medical School has recently completed the second year of a National Library of Medicine grant funded project; the Women’s Health Resources Dissemination Outreach Project. The goals include assisting women’s health researchers by providing them with access to information and making them more aware of opportunities and available resources. This, ultimately, enables both an improvement in women’s health and the advancement of women in academic medicine. Moreover, by supporting women’s health research and women researchers through the objectives of this project, women researchers build connections, knowledge, and skills. This facilitates meaningful contributions and fosters greater promotion and leadership opportunities for these women. This poster describes the goals, activities, and progress of the project through the completion of the second year. Specific programs and initiatives are highlighted. This includes the multi-year endeavor to build, recruit, and showcase women’s health researchers in a specific collection of eScholarship@UMMS, the library’s institutional repository. Promotion and outreach, of both the project and the resources, was major component of the second year. Additionally, programming was developed that helped researchers better communicate their work to the media and public. Other programs, lessons learned, successes, and future goals are noted

Cell Culture Modeling to Test Therapies Against Hyperglycemia-Mediated Oxidative Stress and Injury

The concept that oxidative stress is a key mediator of nerve injury in diabetes has led us to design therapies that target oxidative stress mechanisms. Using an in vitro model of glucose-treated dorsal root ganglion (DRG) neurons in culture, we can examine both free radical generation, using fluorimetric probes for reactive oxygen species, and cell death via the TUNEL assay. The cell culture system is scaled down to a 96-well plate format, and so is well suited to high-throughput screening. In the present study, we test the ability of three drugs, nicotinamide, allopurinol, and α-lipoic acid, alone and in combination to prevent DRG neuron oxidative stress and cell death. This combination of drugs is currently in clinical trial in type 1 diabetic patients. We demonstrate independent effects on oxidative stress and neuronal survival for the three drugs, and neuronal protection using the three drugs in combination. The data strengthen the rationale for the current clinical trial. In addition, we describe an effective tool for rapid preclinical testing of novel therapies against diabetic neuropathy. Antioxid. Redox Signal. 7, 1494–1506.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63115/1/ars.2005.7.1494.pd

Quantitative trait locus-specific genotype × alcoholism interaction on linkage for evoked electroencephalogram oscillations

We explored the evidence for a quantitative trait locus (QTL)-specific genotype × alcoholism interaction for an evoked electroencephalogram theta band oscillation (ERP) phenotype on a region of chromosome 7 in participants of the US Collaborative Study on the Genetics of Alcoholism. Among 901 participants with both genotype and phenotype data available, we performed variance component linkage analysis (SOLAR version 2.1.2) in the full sample and stratified by DSM-III-R and Feighner-definite alcoholism categories. The heritability of the ERP phenotype after adjusting for age and sex effects in the combined sample and in the alcoholism classification sub-groups ranged from 40% to 66%. Linkage on chromosome 7 was identified at 158 cM (LOD = 3.8) in the full sample and at 108 in the non-alcoholic subgroup (LOD = 3.1). Further, we detected QTL-specific genotype × alcoholism interaction at these loci. This work demonstrates the importance of considering the complexity of common complex traits in our search for genes that predispose to alcoholism

Surface Gravities for 228 M, L, and T Dwarfs in the NIRSPEC Brown Dwarf Spectroscopic Survey

We combine 131 new medium-resolution (R~2000) J-band spectra of M, L, and T dwarfs from the Keck NIRSPEC Brown Dwarf Spectroscopic Survey (BDSS) with 97 previously published BDSS spectra to study surface-gravity-sensitive indices for 228 low-mass stars and brown dwarfs spanning spectral types M5-T9. Specifically, we use an established set of spectral indices to determine surface gravity classifications for all M6-L7 objects in our sample by measuring equivalent widths (EW) of the K I lines at 1.1692, 1.1778, 1.2529 um, and the 1.2 um FeHJ absorption index. Our results are consistent with previous surface gravity measurements, showing a distinct double peak - at ~L5 and T5 - in K I EW as a function of spectral type. We analyze K I EWs of 73 objects of known ages and find a linear trend between log(Age) and EW. From this relationship, we assign age ranges to the very low gravity, intermediate gravity, and field gravity designations for spectral types M6-L0. Interestingly, the ages probed by these designations remain broad, change with spectral type, and depend on the gravity sensitive index used. Gravity designations are useful indicators of the possibility of youth, but current datasets cannot be used to provide a precise age estimate.Comment: 33 pages, 13 figures, ApJ in pres