Modulation of genetic associations with serum urate levels by body-mass-index in humans

Documento escrito por un elevado número de autores/as, sólo se referencia el/la que aparece en primer lugar y los/as autores/as pertenecientes a la UC3M.We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment

Association between Medical Student Grit and United States Medical Licensing Examination Performance

Presented as Themed Oral Presentation at the 2020 IUSM Education Da

The effects of postural threat on cognitive strategies used to maintain upright stance

It is well established that postural threat modifies postural control, although little is known regarding the underlying mechanism(s) responsible. It is possible that changes in postural control under conditions of elevated postural threat result from alterations in cognitive strategies. The purpose of this study was to determine the influence of elevated postural threat on cognitive strategies and to determine the relationship between postural control, psychological, and cognitive measures. It was hypothesized that elevated postural threat would cause a shift to more conscious control of posture. It was also expected that a relationship between fear of falling and postural control would exist that could be explained by changes in conscious control of posture. Forty-eight healthy young adults stood on a force plate at two different surface heights: ground level (LOW) and 3.2m above ground level (HIGH). Center of pressure (COP) summary measures calculated to quantify postural control were the mean position (AP-COP MP), root mean square (AP-COP RMS) and mean power frequency (AP-COP MPF) in the anteriorposterior direction. Trunk sway measures calculated in the pitch direction were trunk angle and trunk velocity. Psychological measures including perceived balance confidence, perceived fear of falling, perceived anxiety, and perceived stability were self reported. As a physiological indicator of anxiety, electrodermal activity was collected. The cognitive strategies assessed were movement reinvestment and attention focus. A modified state-sp-ecific version of the Movement Specific Reinvestment Scale was used to measure conscious motor processing (CMP) and movement self-consciousness (MSC). An attention focus questionnaire was developed to assess the amount of attention directed to internal and external sources. An effect of postural threat on cognitive strategies was observed as participants reported more conscious control and a greater concern or worry about their posture at the HIGH postural threat condition as well as an increased internal and external focus of attention. In addition changes in postural control, psychological, and physiological measures were found. The participants leaned away from the edge of the platform, the frequency of their postural adjustments increased, and the velocity of their trunk movements increased. Participants felt less confident, more fearful, more anxious, and less stable with an accompanying increase in physiological anxiety. Significant correlations between perceived anxiety, AP-COP MP, and cognitive measures revealed a possible relationship that could be mediated by cognitive measures. It was found that with greater conscious motor processing, more movement self-consciousness, and a greater amount of attention focused externally there was a larger shift of the mean position away from the edge of the platform. This thesis provides evidence that postural threat can influence cognitive strategies causing a shift to more conscious control of movement which is associated with leaning away from the edge of the platform. Shifting the position of the body away from the direction of the postural threat may reflect a cognitive strategy to ensure safety in this situation due to the inability to employ a stepping strategy when standing on an elevated platform

Recruiting for your Department: The Role of the Chair

The chairs of an Education, Sports & Exercise Science, and Psychology Departments, and their former dean, share how they have been able to implement innovative recruitment strategies from an academic standpoint to increase enrollment in their departments and in the School of Graduate and Professional Studies

Genetic analysis of protein N-Glycosylation

The majority of human proteins are post-translationally modified by covalent addition of one or more complex oligosaccharides (glycans). Alterations in glycosylation processing are associated with numerous diseases and glycans are attracting increasing attention both as disease biomarkers and as targets for novel therapeutic approaches. Using a recently developed high performance liquid chromatography (HPLC) method for high-throughput glycan analysis, genome-wide association studies (GWAS) of 33 directly measured and 13 derived N-glycan features were performed in 3533 individuals from four European isolated populations. Polymorphisms at six loci were found to show genome-wide significant association with plasma concentrations of N-glycans. Several of these gene products have well characterised roles in glycosylation, however, SLC9A9 and HNF1A were two of the novel findings. Subsequent work performed by collaborators found HNF1A to be a “master regulator” of genes involved in the fucosylation of plasma N-glycans. Additionally, this work led to the discovery that N-glycans could act as biomarkers to discriminate HNF1A-MODY from type 1 and type 2 diabetes mellitus (T1D, T2D) patients. After the success of the total plasma N-glycan GWAS, it was thought that stronger and more biologically interpretable associations may be found from the investigation of N-glycans isolated from a single protein. Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. To identify genetic networks that govern IgG glycosylation, N-linked IgG glycans were quantitated using ultra performance liquid chromatography (UPLC) in 2247 individuals from the same four European populations from the previous study. GWAS of the 77 N-glycan measures identified 15 loci with a p-value<5x10-08. Four loci contained genes encoding glycosyltransferases, while the remaining loci contained genes that have not previously been implicated in protein glycosylation. However, most have been associated with autoimmune and inflammatory conditions and/or hematological cancers. Several high-throughput methods for the analysis of N-glycans have been developed in the past few years but thorough validation and standardization of these methods is required before significant resources are invested in large-scale studies. To this end, four of these methods were compared, UPLC, multiplexed capillary gel electrophoresis (xCGE), and two mass spectrometric (MS) methods, for quantitative profiling of N-glycosylation of plasma IgG in a subset of 1201 individuals recruited from two of the cohorts used in the previous GWAS studies. A “minimal” dataset was compiled of N-glycan structures able to be measured by all four methods. To evaluate their accuracy, correlations were calculated for each structure in the minimal dataset. Additionally, GWAS was performed to test if the same associations would be observed across methodologies. Chromatographic methods with either fluorescent or MS-detection yielded slightly stronger associations than MS-only and xCGE, but at the expense of lower levels of throughput. Advantages and disadvantages of each method were identified, which should aid in the selection of the most appropriate method for future studies. This work shows that it is possible to identify new loci that control glycosylation of plasma proteins using GWAS and the potential of N-glycans for biomarker development. It also provides some guidelines for methodology selection for future studies of N-glycans

Leading In A Perpetual State Of Change

Three academic chairs and their dean will provide examples of how they have led through the difficult and ever-changing higher education landscape. Topics will include faculty turnover, budget cuts, and university restructuring. The audience will be invited to share their own experiences and recommendations will be provided

Joining Forces: Fostering Creativity and Success across Departments

The chairs of a Psychology, Education, and Sports & Exercise Science Department and their dean share how they have been able to apply a model of collaborative creativity (Paulus & Dzindolet, 2008) to promote teamwork and innovation in their departments and in the School

Clinical and Demographic Predictors of Interdisciplinary Chronic Pain Rehabilitation Program Treatment Response

© 2019 the American Pain Society Patients treated in interdisciplinary chronic pain rehabilitation programs show long-term improvements in symptoms; however, outcomes may vary across heterogenous patient subpopulations. This longitudinal retrospective study characterizes the influence of opioids, mood, patient characteristics, and baseline symptoms on pain and functional impairment (FI) in 1,681 patients 6-months to 12-months post-treatment in an interdisciplinary chronic pain rehabilitation program incorporating opioid weaning. Linear mixed models showed immediate and durable treatment benefits with nonuniform worsening at follow up which slowed over time. Latent class growth analysis identified three post-treatment trajectories of pain and FI: mild symptoms and durable benefits, moderate symptoms and durable benefits, and intractable symptoms. A fourth pain trajectory showed immediate post-treatment improvement and worsening at follow up. Whether a patient was weaned from opioids was not predictive of treatment trajectory. Racial ethnic minority status, higher levels of post-treatment depression, and lower perceived treatment response were associated with less resolution (moderate symptoms) or intractable symptoms. Not having a college education was predictive of intractable or worsening pain and a moderate course of FI. Older age and male gender was associated with intractable FI. Treatment outcomes may be improved by the development of targeted interventions for patients at risk of poor recovery and/or deteriorating long-term course. Perspective: This study examined predictors of treatment response in 1,681 patients treated in an interdisciplinary chronic pain rehabilitation program incorporating opioid weaning. Opioid weaning did not predict outcome. Higher levels of symptoms, lower levels of education, and being a racial-ethnic minority were associated with a less salubrious long-term treatment response