Examining the role of unmeasured confounding in mediation analysis with genetic and genomic applications.

PubMed

Lutz, Sharon M; Thwing, Annie; Schmiege, Sarah; Kroehl, Miranda; Baker, Christopher D; Starling, Anne P; Hokanson, John E; Ghosh, Debashis

2017-07-19

In mediation analysis if unmeasured confounding is present, the estimates for the direct and mediated effects may be over or under estimated. Most methods for the sensitivity analysis of unmeasured confounding in mediation have focused on the mediator-outcome relationship. The Umediation R package enables the user to simulate unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships in order to see how the results of the mediation analysis would change in the presence of unmeasured confounding. We apply the Umediation package to the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) study to examine the role of unmeasured confounding due to population stratification on the effect of a single nucleotide polymorphism (SNP) in the CHRNA5/3/B4 locus on pulmonary function decline as mediated by cigarette smoking. Umediation is a flexible R package that examines the role of unmeasured confounding in mediation analysis allowing for normally distributed or Bernoulli distributed exposures, outcomes, mediators, measured confounders, and unmeasured confounders. Umediation also accommodates multiple measured confounders, multiple unmeasured confounders, and allows for a mediator-exposure interaction on the outcome. Umediation is available as an R package at https://github.com/SharonLutz/Umediation A tutorial on how to install and use the Umediation package is available in the Additional file 1.

On the Interpretation and Use of Mediation: Multiple Perspectives on Mediation Analysis

PubMed Central

Agler, Robert; De Boeck, Paul

2017-01-01

Mediation analysis has become a very popular approach in psychology, and it is one that is associated with multiple perspectives that are often at odds, often implicitly. Explicitly discussing these perspectives and their motivations, advantages, and disadvantages can help to provide clarity to conversations and research regarding the use and refinement of mediation models. We discuss five such pairs of perspectives on mediation analysis, their associated advantages and disadvantages, and their implications: with vs. without a mediation hypothesis, specific effects vs. a global model, directness vs. indirectness of causation, effect size vs. null hypothesis testing, and hypothesized vs. alternative explanations. Discussion of the perspectives is facilitated by a small simulation study. Some philosophical and linguistic considerations are briefly discussed, as well as some other perspectives we do not develop here. PMID:29187828

A Statistical Method for Synthesizing Mediation Analyses Using the Product of Coefficient Approach Across Multiple Trials

PubMed Central

Huang, Shi; MacKinnon, David P.; Perrino, Tatiana; Gallo, Carlos; Cruden, Gracelyn; Brown, C Hendricks

2016-01-01

Mediation analysis often requires larger sample sizes than main effect analysis to achieve the same statistical power. Combining results across similar trials may be the only practical option for increasing statistical power for mediation analysis in some situations. In this paper, we propose a method to estimate: 1) marginal means for mediation path a, the relation of the independent variable to the mediator; 2) marginal means for path b, the relation of the mediator to the outcome, across multiple trials; and 3) the between-trial level variance-covariance matrix based on a bivariate normal distribution. We present the statistical theory and an R computer program to combine regression coefficients from multiple trials to estimate a combined mediated effect and confidence interval under a random effects model. Values of coefficients a and b, along with their standard errors from each trial are the input for the method. This marginal likelihood based approach with Monte Carlo confidence intervals provides more accurate inference than the standard meta-analytic approach. We discuss computational issues, apply the method to two real-data examples and make recommendations for the use of the method in different settings. PMID:28239330

Practical guidance for conducting mediation analysis with multiple mediators using inverse odds ratio weighting.

PubMed

Nguyen, Quynh C; Osypuk, Theresa L; Schmidt, Nicole M; Glymour, M Maria; Tchetgen Tchetgen, Eric J

2015-03-01

Despite the recent flourishing of mediation analysis techniques, many modern approaches are difficult to implement or applicable to only a restricted range of regression models. This report provides practical guidance for implementing a new technique utilizing inverse odds ratio weighting (IORW) to estimate natural direct and indirect effects for mediation analyses. IORW takes advantage of the odds ratio's invariance property and condenses information on the odds ratio for the relationship between the exposure (treatment) and multiple mediators, conditional on covariates, by regressing exposure on mediators and covariates. The inverse of the covariate-adjusted exposure-mediator odds ratio association is used to weight the primary analytical regression of the outcome on treatment. The treatment coefficient in such a weighted regression estimates the natural direct effect of treatment on the outcome, and indirect effects are identified by subtracting direct effects from total effects. Weighting renders treatment and mediators independent, thereby deactivating indirect pathways of the mediators. This new mediation technique accommodates multiple discrete or continuous mediators. IORW is easily implemented and is appropriate for any standard regression model, including quantile regression and survival analysis. An empirical example is given using data from the Moving to Opportunity (1994-2002) experiment, testing whether neighborhood context mediated the effects of a housing voucher program on obesity. Relevant Stata code (StataCorp LP, College Station, Texas) is provided. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Causal mediation analysis with multiple causally non-ordered mediators.

PubMed

Taguri, Masataka; Featherstone, John; Cheng, Jing

2018-01-01

In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

A Mediation Analysis of a Tobacco Prevention Program for Adolescents in India: How Did Project MYTRI Work?

ERIC Educational Resources Information Center

Stigler, Melissa Harrell; Perry, Cheryl L.; Smolenski, Derek; Arora, Monika; Reddy, K. Srinath

2011-01-01

This article presents the results of a mediation analysis of Project MYTRI (Mobilizing Youth for Tobacco Related Initiatives in India), a randomized, controlled trial of a multiple-component, school-based tobacco prevention program for sixth- to ninth-graders (n = 14,085) in Delhi and Chennai, India. A mediation analysis identifies "how"…

Mediation Analysis of an Adolescent HIV/STI/Pregnancy Prevention Intervention

ERIC Educational Resources Information Center

Glassman, Jill R.; Franks, Heather M.; Baumler, Elizabeth R.; Coyle, Karin K.

2014-01-01

Most interventions designed to prevent HIV/STI/pregnancy risk behaviours in young people have multiple components based on psychosocial theories (e.g. social cognitive theory) dictating sets of mediating variables to influence to achieve desired changes in behaviours. Mediation analysis is a method for investigating the extent to which a variable…

Morphological Awareness in Vocabulary Acquisition among Chinese-Speaking Children: Testing Partial Mediation via Lexical Inference Ability

ERIC Educational Resources Information Center

Zhang, Haomin

2015-01-01

The goal of this study was to investigate the effect of Chinese-specific morphological awareness on vocabulary acquisition among young Chinese-speaking students. The participants were 288 Chinese-speaking second graders from three different cities in China. Multiple regression analysis and mediation analysis were used to uncover the mediated and…

A longitudinal examination of the interrelationship of multiple health behaviors.

PubMed

deRuiter, Wayne K; Cairney, John; Leatherdale, Scott T; Faulkner, Guy E J

2014-09-01

Evaluating the interrelationship of health behaviors could assist in the development of effective public health interventions. Furthermore, the ability to identify cognitive mediators that may influence multiple behavioral changes requires evaluation. To evaluate covariation among health behaviors, specifically alcohol consumption, leisure-time physical activity, and smoking, and examine whether mastery acts as a mediating social-cognitive mechanism that facilitates multiple health behavior change in a longitudinal analysis. In 2010, secondary data analysis was conducted on the first seven cycles of the Canadian National Population Health Survey. Data collection began in 1994-1995 and has continued biennially. At the time of this analysis, only seven cycles of data (2006-2007) were available. Parallel process growth curve models were used to analyze covariation between health behaviors and the potential mediating effects of perceived mastery. Increases in leisure-time physical activity were associated with reductions in tobacco use, whereas declines in alcohol consumption were associated with decreases in tobacco use. Covariation between alcohol consumption and leisure-time physical activity did not reach statistical significance. For the most part, mastery was unsuccessful in mediating the interrelationship of multiple behavioral changes. Health behaviors are not independent but rather interrelated. In order to optimize limited prevention resources, these results suggest that population-level intervention efforts targeting multiple modifiable behavioral risk factors may not need to occur simultaneously. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Cognitive and affective mechanisms of pain and fatigue in multiple sclerosis.

PubMed

Arewasikporn, Anne; Turner, Aaron P; Alschuler, Kevin N; Hughes, Abbey J; Ehde, Dawn M

2018-06-01

To examine the extent to which pain catastrophizing, fatigue catastrophizing, positive affect, and negative affect simultaneously mediated the associations between common symptoms of multiple sclerosis (MS; i.e., pain, fatigue) and impact on daily life, depressive symptoms, and resilience. Participants were community-dwelling adults with MS (N = 163) reporting chronic pain, fatigue, and/or moderate depressive symptoms. Multiple mediation path analysis was used to model potential mediators of pain and fatigue separately, using baseline data from a randomized controlled trial comparing two symptom self-management interventions. In the pain model, pain catastrophizing was a mediator of pain intensity with pain interference and depression. Negative affect was a mediator of pain intensity with depression and resilience. In the fatigue model, fatigue catastrophizing was a mediator of fatigue intensity with fatigue impact and depression. Positive affect was a mediator of fatigue intensity with depression and resilience. These findings provide preliminary support for the presence of differential effects of cognitive-affective mediators and suggest potential targets for psychological interventions based on an individual's clinical presentation. The differential mediating effects also support the inclusion of both positive and negative aspects of psychological health in models of pain and fatigue, which would not be otherwise apparent if negative constructs were examined in isolation. To our knowledge, this is the first study to utilize a multivariate path analysis approach to examine cognitive-affective mediators of pain and fatigue in MS, while also examining positive and negative constructs concurrently. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Childhood trauma and eating psychopathology: a mediating role for dissociation and emotion dysregulation?

PubMed

Moulton, Stuart J; Newman, Emily; Power, Kevin; Swanson, Vivien; Day, Kenny

2015-01-01

The present study examined the relationship between different forms of childhood trauma and eating psychopathology using a multiple mediation model that included emotion dysregulation and dissociation as hypothesised mediators. 142 female undergraduate psychology students studying at two British Universities participated in this cross-sectional study. Participants completed measures of childhood trauma (emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect), eating psychopathology, dissociation and emotion dysregulation. Multiple mediation analysis was conducted to investigate the study's proposed model. Results revealed that the multiple mediation model significantly predicted eating psychopathology. Additionally, both emotion dysregulation and dissociation were found to be significant mediators between childhood trauma and eating psychopathology. A specific indirect effect was observed between childhood emotional abuse and eating psychopathology through emotion dysregulation. Findings support previous research linking childhood trauma to eating psychopathology. They indicate that multiple forms of childhood trauma should be assessed for individuals with eating disorders. The possible maintaining role of emotion regulation processes should also be considered in the treatment of eating disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cortical surface-based threshold-free cluster enhancement and cortexwise mediation.

PubMed

Lett, Tristram A; Waller, Lea; Tost, Heike; Veer, Ilya M; Nazeri, Arash; Erk, Susanne; Brandl, Eva J; Charlet, Katrin; Beck, Anne; Vollstädt-Klein, Sabine; Jorde, Anne; Kiefer, Falk; Heinz, Andreas; Meyer-Lindenberg, Andreas; Chakravarty, M Mallar; Walter, Henrik

2017-06-01

Threshold-free cluster enhancement (TFCE) is a sensitive means to incorporate spatial neighborhood information in neuroimaging studies without using arbitrary thresholds. The majority of methods have applied TFCE to voxelwise data. The need to understand the relationship among multiple variables and imaging modalities has become critical. We propose a new method of applying TFCE to vertexwise statistical images as well as cortexwise (either voxel- or vertexwise) mediation analysis. Here we present TFCE_mediation, a toolbox that can be used for cortexwise multiple regression analysis with TFCE, and additionally cortexwise mediation using TFCE. The toolbox is open source and publicly available (https://github.com/trislett/TFCE_mediation). We validated TFCE_mediation in healthy controls from two independent multimodal neuroimaging samples (N = 199 and N = 183). We found a consistent structure-function relationship between surface area and the first independent component (IC1) of the N-back task, that white matter fractional anisotropy is strongly associated with IC1 N-back, and that our voxel-based results are essentially identical to FSL randomise using TFCE (all P FWE <0.05). Using cortexwise mediation, we showed that the relationship between white matter FA and IC1 N-back is mediated by surface area in the right superior frontal cortex (P FWE  < 0.05). We also demonstrated that the same mediation model is present using vertexwise mediation (P FWE  < 0.05). In conclusion, cortexwise analysis with TFCE provides an effective analysis of multimodal neuroimaging data. Furthermore, cortexwise mediation analysis may identify or explain a mechanism that underlies an observed relationship among a predictor, intermediary, and dependent variables in which one of these variables is assessed at a whole-brain scale. Hum Brain Mapp 38:2795-2807, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Rumination mediates the relationship between overgeneral autobiographical memory and depression in patients with major depressive disorder.

PubMed

Liu, Yansong; Yu, Xinnian; Yang, Bixiu; Zhang, Fuquan; Zou, Wenhua; Na, Aiguo; Zhao, Xudong; Yin, Guangzhong

2017-03-21

Overgeneral autobiographical memory has been identified as a risk factor for the onset and maintenance of depression. However, little is known about the underlying mechanisms that might explain overgeneral autobiographical memory phenomenon in depression. The purpose of this study was to test the mediation effects of rumination on the relationship between overgeneral autobiographical memory and depressive symptoms. Specifically, the mediation effects of brooding and reflection subtypes of rumination were examined in patients with major depressive disorder. Eighty-seven patients with major depressive disorder completed the 17-item Hamilton Depression Rating Scale, Ruminative Response Scale, and Autobiographical Memory Test. Bootstrap mediation analysis for simple and multiple mediation models through the PROCESS macro was applied. Simple mediation analysis showed that rumination significantly mediated the relationship between overgeneral autobiographical memory and depression symptoms. Multiple mediation analyses showed that brooding, but not reflection, significantly mediated the relationship between overgeneral autobiographical memory and depression symptoms. Our results indicate that global rumination partly mediates the relationship between overgeneral autobiographical memory and depressive symptoms in patients with major depressive disorder. Furthermore, the present results suggest that the mediating role of rumination in the relationship between overgeneral autobiographical memory and depression is mainly due to the maladaptive brooding subtype of rumination.

The role of appraisal and coping style in relation with societal participation in fatigued patients with multiple sclerosis: a cross-sectional multiple mediator analysis.

PubMed

van den Akker, Lizanne Eva; Beckerman, Heleen; Collette, Emma Hubertine; Bleijenberg, Gijs; Dekker, Joost; Knoop, Hans; de Groot, Vincent

2016-10-01

To determine the relationship between appraisal and societal participation in fatigued patients with Multiple Sclerosis (MS), and whether this relation is mediated by coping styles. 265 severely-fatigued MS patients. Appraisal, a latent construct, was created from the General Self-Efficacy Scale and the helplessness and acceptance subscales of the Illness Cognition Questionnaire. Coping styles were assessed using the Coping Inventory Stressful Situations (CISS21) and societal participation was assessed using the Impact on Participation and Autonomy. A multiple mediator model was developed and tested by structural equation modeling on cross-sectional data. We corrected for confounding by disease-related factors. Mediation was determined using a product-of-coefficients approach. A significant relationship existed between appraisal and participation (β = 0.21, 95 % CI 0.04-0.39). The pathways via coping styles were not significant. In patients with severe MS-related fatigue, appraisal and societal participation show a positive relationship that is not mediated by coping styles.

Statistical grand rounds: understanding the mechanism: mediation analysis in randomized and nonrandomized studies.

PubMed

Mascha, Edward J; Dalton, Jarrod E; Kurz, Andrea; Saager, Leif

2013-10-01

In comparative clinical studies, a common goal is to assess whether an exposure, or intervention, affects the outcome of interest. However, just as important is to understand the mechanism(s) for how the intervention affects outcome. For example, if preoperative anemia was shown to increase the risk of postoperative complications by 15%, it would be important to quantify how much of that effect was due to patients receiving intraoperative transfusions. Mediation analysis attempts to quantify how much, if any, of the effect of an intervention on outcome goes though prespecified mediator, or "mechanism" variable(s), that is, variables sitting on the causal pathway between exposure and outcome. Effects of an exposure on outcome can thus be divided into direct and indirect, or mediated, effects. Mediation is claimed when 2 conditions are true: the exposure affects the mediator and the mediator (adjusting for the exposure) affects the outcome. Understanding how an intervention affects outcome can validate or invalidate one's original hypothesis and also facilitate further research to modify the responsible factors, and thus improve patient outcome. We discuss the proper design and analysis of studies investigating mediation, including the importance of distinguishing mediator variables from confounding variables, the challenge of identifying potential mediators when the exposure is chronic versus acute, and the requirements for claiming mediation. Simple designs are considered, as well as those containing multiple mediators, multiple outcomes, and mixed data types. Methods are illustrated with data collected by the National Surgical Quality Improvement Project (NSQIP) and utilized in a companion paper which assessed the effects of preoperative anemic status on postoperative outcomes.

Multiple Mediation Analysis of the Relationship between Rapid Naming and Reading

ERIC Educational Resources Information Center

Poulsen, Mads; Juul, Holger; Elbro, Carsten

2015-01-01

It is well established that rapid automatised naming (RAN) correlates with reading ability. Despite several attempts, no single component process (mediator) has been identified that fully accounts for the correlation. The present paper estimated the explanatory value of several mediators for the RAN--reading correlation. One hundred and sixty-nine…

A combined planning and self-efficacy intervention to promote physical activity: a multiple mediation analysis.

PubMed

Koring, Milena; Richert, Jana; Parschau, Linda; Ernsting, Anna; Lippke, Sonia; Schwarzer, Ralf

2012-01-01

Many individuals are motivated to improve their physical activity levels, but often fail to act upon their intention. Interventions fostering volitional strategies, such as action planning, coping planning, and self-efficacy beliefs, can help to translate intentions into behavior. This study examines the effectiveness and the mechanisms of a combined planning and self-efficacy intervention to promote physical activity among motivated individuals. Participants (N = 883) were randomly assigned to the intervention or to a waiting-list control condition. Multivariate analysis of variance revealed that the intervention resulted in significantly more physical activity, higher levels of action planning, coping planning, and volitional self-efficacy beliefs (p < 0.01). In addition, multiple mediation analysis showed that action planning, coping planning, and volitional self-efficacy mediate between the intervention and physical activity. The study shows that the intervention successfully fostered physical activity and unfolds the underlying self-regulatory mechanisms of the intervention's effectiveness.

The Relationship of Core Self-Evaluations and Life Satisfaction in College Students with Disabilities: Evaluation of a Mediator Model

ERIC Educational Resources Information Center

Smedema, Susan Miller; Chan, Fong; Yaghmaian, Rana A.; Cardoso, Elizabeth DaSilva; Muller, Veronica; Keegan, John; Dutta, Alo; Ebener, Deborah J.

2015-01-01

This study examined the factorial structure of the construct core self-evaluations (CSE) and tested a mediational model of the relationship between CSE and life satisfaction in college students with disabilities. We conducted a quantitative descriptive design using exploratory and confirmatory factor analysis and multiple regression analysis.…

Causal mediation analysis with a binary outcome and multiple continuous or ordinal mediators: Simulations and application to an alcohol intervention.

PubMed

Nguyen, Trang Quynh; Webb-Vargas, Yenny; Koning, Ina M; Stuart, Elizabeth A

We investigate a method to estimate the combined effect of multiple continuous/ordinal mediators on a binary outcome: 1) fit a structural equation model with probit link for the outcome and identity/probit link for continuous/ordinal mediators, 2) predict potential outcome probabilities, and 3) compute natural direct and indirect effects. Step 2 involves rescaling the latent continuous variable underlying the outcome to address residual mediator variance/covariance. We evaluate the estimation of risk-difference- and risk-ratio-based effects (RDs, RRs) using the ML, WLSMV and Bayes estimators in Mplus. Across most variations in path-coefficient and mediator-residual-correlation signs and strengths, and confounding situations investigated, the method performs well with all estimators, but favors ML/WLSMV for RDs with continuous mediators, and Bayes for RRs with ordinal mediators. Bayes outperforms WLSMV/ML regardless of mediator type when estimating RRs with small potential outcome probabilities and in two other special cases. An adolescent alcohol prevention study is used for illustration.

The mediator effect of personality traits on the relationship between childhood abuse and depressive symptoms in schizophrenia.

PubMed

Okubo, Ryo; Inoue, Takeshi; Hashimoto, Naoki; Suzukawa, Akio; Tanabe, Hajime; Oka, Matsuhiko; Narita, Hisashi; Ito, Koki; Kako, Yuki; Kusumi, Ichiro

2017-11-01

Previous studies indicated that personality traits have a mediator effect on the relationship between childhood abuse and depressive symptoms in major depressive disorder and nonclinical general adult subjects. In the present study, we aimed to test the hypothesis that personality traits mediate the relationship between childhood abuse and depressive symptoms in schizophrenia. We used the following questionnaires to evaluate 255 outpatients with schizophrenia: the Child Abuse and Trauma Scale, temperament and character inventory, and Patients Health Questionnire-9. Univariate analysis, multiple regression analysis, and structured equation modeling (SEM) were used to analyze the data. The relationship between neglect and sexual abuse and the severity of depressive symptoms was mostly mediated by the personality traits of high harm avoidance, low self-directedness, and low cooperativeness. This finding was supported by the results of stepwise multiple regression analysis and the acceptable fit indices of SEM. Thus, our results suggest that personality traits mediate the relationship between childhood abuse and depressive symptoms in schizophrenia. The present study and our previous studies also suggest that this mediator effect could occur independent of the presence or type of mental disorder. Clinicians should routinely assess childhood abuse history, personality traits, and their effects in schizophrenia. Copyright © 2017. Published by Elsevier B.V.

Direct and indirect influences of fate control belief, gambling expectancy bias, and self-efficacy on problem gambling and negative mood among Chinese college students: a multiple mediation analysis.

PubMed

Tang, Catherine So-Kum; Wu, Anise M S

2010-12-01

A multiple mediation model was proposed to integrate core concepts of the social axioms framework and the social cognitive theory in order to understand gambling behavior. It was hypothesized that the influence of general fate control belief on problem gambling and negative mood would be mediated by gambling-specific beliefs. Data from 773 Chinese college recreational gamblers were collected. The bootstrapping procedure was used to test the multiple mediation hypotheses. Significant indirect effects of fate control belief on problem gambling and negative mood through two gambling-specific mediators were found. Gambling expectancy bias was a more salient mediator than gambling self-efficacy. Fate control belief was also found to have a significant direct effect on negative mood. In general, a high level of general fate control belief was related to greater gambling expectancy bias and lower self-efficacy in resisting gambling, which were in turn related to problem gambling and negative mood. Limitations and implications of the study were discussed.

Flexible Mediation Analysis With Multiple Mediators.

PubMed

Steen, Johan; Loeys, Tom; Moerkerke, Beatrijs; Vansteelandt, Stijn

2017-07-15

The advent of counterfactual-based mediation analysis has triggered enormous progress on how, and under what assumptions, one may disentangle path-specific effects upon combining arbitrary (possibly nonlinear) models for mediator and outcome. However, current developments have largely focused on single mediators because required identification assumptions prohibit simple extensions to settings with multiple mediators that may depend on one another. In this article, we propose a procedure for obtaining fine-grained decompositions that may still be recovered from observed data in such complex settings. We first show that existing analytical approaches target specific instances of a more general set of decompositions and may therefore fail to provide a comprehensive assessment of the processes that underpin cause-effect relationships between exposure and outcome. We then outline conditions for obtaining the remaining set of decompositions. Because the number of targeted decompositions increases rapidly with the number of mediators, we introduce natural effects models along with estimation methods that allow for flexible and parsimonious modeling. Our procedure can easily be implemented using off-the-shelf software and is illustrated using a reanalysis of the World Health Organization's Large Analysis and Review of European Housing and Health Status (WHO-LARES) study on the effect of mold exposure on mental health (2002-2003). © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A default Bayesian hypothesis test for mediation.

PubMed

Nuijten, Michèle B; Wetzels, Ruud; Matzke, Dora; Dolan, Conor V; Wagenmakers, Eric-Jan

2015-03-01

In order to quantify the relationship between multiple variables, researchers often carry out a mediation analysis. In such an analysis, a mediator (e.g., knowledge of a healthy diet) transmits the effect from an independent variable (e.g., classroom instruction on a healthy diet) to a dependent variable (e.g., consumption of fruits and vegetables). Almost all mediation analyses in psychology use frequentist estimation and hypothesis-testing techniques. A recent exception is Yuan and MacKinnon (Psychological Methods, 14, 301-322, 2009), who outlined a Bayesian parameter estimation procedure for mediation analysis. Here we complete the Bayesian alternative to frequentist mediation analysis by specifying a default Bayesian hypothesis test based on the Jeffreys-Zellner-Siow approach. We further extend this default Bayesian test by allowing a comparison to directional or one-sided alternatives, using Markov chain Monte Carlo techniques implemented in JAGS. All Bayesian tests are implemented in the R package BayesMed (Nuijten, Wetzels, Matzke, Dolan, & Wagenmakers, 2014).

Causal mediation analysis with multiple mediators.

PubMed

Daniel, R M; De Stavola, B L; Cousens, S N; Vansteelandt, S

2015-03-01

In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

PubMed

Huang, Yen-Tsung; Yang, Hwai-I

2017-05-01

Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

Mediation Analysis: A Practitioner's Guide.

PubMed

VanderWeele, Tyler J

2016-01-01

This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.

Applying causal mediation analysis to personality disorder research.

PubMed

Walters, Glenn D

2018-01-01

This article is designed to address fundamental issues in the application of causal mediation analysis to research on personality disorders. Causal mediation analysis is used to identify mechanisms of effect by testing variables as putative links between the independent and dependent variables. As such, it would appear to have relevance to personality disorder research. It is argued that proper implementation of causal mediation analysis requires that investigators take several factors into account. These factors are discussed under 5 headings: variable selection, model specification, significance evaluation, effect size estimation, and sensitivity testing. First, care must be taken when selecting the independent, dependent, mediator, and control variables for a mediation analysis. Some variables make better mediators than others and all variables should be based on reasonably reliable indicators. Second, the mediation model needs to be properly specified. This requires that the data for the analysis be prospectively or historically ordered and possess proper causal direction. Third, it is imperative that the significance of the identified pathways be established, preferably with a nonparametric bootstrap resampling approach. Fourth, effect size estimates should be computed or competing pathways compared. Finally, investigators employing the mediation method are advised to perform a sensitivity analysis. Additional topics covered in this article include parallel and serial multiple mediation designs, moderation, and the relationship between mediation and moderation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Parental drinking as a risk factor for children's maladjustment: the mediating role of family environment.

PubMed

Bijttebier, Patricia; Goethals, Eveline

2006-06-01

In the present study, the relationships among parental drinking, family environment, and child adjustment is investigated in a community sample of 207 10-14-year-olds. Multiple aspects of perceived family environment (e.g., cohesion, organization, conflict) as well as multiple indicators of adjustment (e.g., negative affect, feelings of competence, self-esteem) are taken into consideration. Parental alcohol problems are found to be associated with low family cohesion, poor family organization, and low global self-worth of the child. A mediational analysis reveals that the relation between parental drinking and low global self-worth is mediated by family cohesion.

Relationship between cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers: Exploring multiple mediation model.

PubMed

Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui

2017-10-01

The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.

Causal mediation analysis with a binary outcome and multiple continuous or ordinal mediators: Simulations and application to an alcohol intervention

PubMed Central

Nguyen, Trang Quynh; Webb-Vargas, Yenny; Koning, Ina M.; Stuart, Elizabeth A.

2016-01-01

We investigate a method to estimate the combined effect of multiple continuous/ordinal mediators on a binary outcome: 1) fit a structural equation model with probit link for the outcome and identity/probit link for continuous/ordinal mediators, 2) predict potential outcome probabilities, and 3) compute natural direct and indirect effects. Step 2 involves rescaling the latent continuous variable underlying the outcome to address residual mediator variance/covariance. We evaluate the estimation of risk-difference- and risk-ratio-based effects (RDs, RRs) using the ML, WLSMV and Bayes estimators in Mplus. Across most variations in path-coefficient and mediator-residual-correlation signs and strengths, and confounding situations investigated, the method performs well with all estimators, but favors ML/WLSMV for RDs with continuous mediators, and Bayes for RRs with ordinal mediators. Bayes outperforms WLSMV/ML regardless of mediator type when estimating RRs with small potential outcome probabilities and in two other special cases. An adolescent alcohol prevention study is used for illustration. PMID:27158217

The Impact of Learner Characteristics on the Multi-Dimensional Construct of Social Presence

ERIC Educational Resources Information Center

Mykota, David

2017-01-01

This study explored the impact of learner characteristics on the multi-dimensional construct of social presence as measured by the computer-mediated communication questionnaire. Using Multiple Analysis of Variance findings reveal that the number of online courses taken and computer-mediated communication experience significantly affect the…

Motivation and Self-Management Behavior of the Individuals With Chronic Low Back Pain.

PubMed

Jung, Mi Jung; Jeong, Younhee

2016-01-01

Self-management behavior is an important component for successful pain management in individuals with chronic low back pain. Motivation has been considered as an effective way to change behavior. Because there are other physical, social, and psychological factors affecting individuals with pain, it is necessary to identify the main effect of motivation on self-management behavior without the influence of those factors. The purpose of this study was to investigate the effect of motivation on self-management in controlling pain, depression, and social support. We used a nonexperimental, cross-sectional, descriptive design with mediation analysis and included 120 participants' data in the final analysis. We also used hierarchical multiple regression to test the effect of motivation, and multiple regression analysis and Sobel test were used to examine the mediating effect. Motivation itself accounted for 23.4% of the variance in self-management, F(1, 118) = 35.003, p < .001. After controlling covariates, motivation was also a significant factor for self-management. In the mediation analysis, motivation completely mediated the relationship between education and self-management, z = 2.292, p = .021. Motivation is an important part of self-management, and self-management education is not effective without motivation. The results of our study suggest that nurses incorporate motivation in nursing intervention, rather than only giving information.

Can job redesign interventions influence a broad range of employee outcomes by changing multiple job characteristics? A quasi-experimental study.

PubMed

Holman, David; Axtell, Carolyn

2016-07-01

Many job redesign interventions are based on a multiple mediator-multiple outcome model in which the job redesign intervention indirectly influences a broad range of employee outcomes by changing multiple job characteristics. As this model remains untested, the aim of this study is to test a multiple mediator-multiple outcome model of job redesign. Multilevel analysis of data from a quasi-experimental job redesign intervention in a call center confirmed the hypothesized model and showed that the job redesign intervention affected a broad range of employee outcomes (i.e., employee well-being, psychological contract fulfillment, and supervisor-rated job performance) through changes in 2 job characteristics (i.e., job control and feedback). The results provide further evidence for the efficacy and mechanisms of job redesign interventions. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Reconceptualizing decisional balance in an adolescent sun protection intervention: mediating effects and theoretical interpretations.

PubMed

Adams, Marc A; Norman, Gregory J; Hovell, Melbourne F; Sallis, James F; Patrick, Kevin

2009-03-01

The Transtheoretical model (TTM) integrates principles of operant learning, such as stimulus control and reinforcement, and psychological factors, such as decisional balance. Understanding interrelationships between decisions, behavior, and consequences from multiple-theoretical perspectives can advance theory and inform development of more effective interventions. This analysis examined the mediating effects of a special case of the decisional balance construct in which the pros of competing behaviors (i.e., sun protection vs. exposure) were measured rather than the pros and cons of the same behavior. Participants included 819 adolescents (10 to 16 years old, 53.5% girls, 58.4% White) randomized to a 24-month expert system intervention (SunSmart) or a physical activity and nutrition comparison group. Self-report measures included sun protection behaviors, pros for protection, and pros for exposure. Mediation analysis using latent growth curve models found both the treatment-to-mediator and mediator-to-behavior paths significant for decisional balance, producing an indirect effect of .323 (p < .01) and good model fit (CFI = .973, RMSEA = .055). Multiple strategies for conceptualizing and measuring decisional balance appear to be valid. Results are interpreted from the TTM and operant perspectives. (c) 2009 APA, all rights reserved

Gender difference in sickness absence from work: a multiple mediation analysis of psychosocial factors.

PubMed

Casini, Annalisa; Godin, Isabelle; Clays, Els; Kittel, France

2013-08-01

Previous research has shown that job characteristics, private life and psychosocial factors partially account for gender difference in work absences because of sickness. Most studies have analysed these factors separately. The aim of the present study was to evaluate whether these explanatory factors act as mediators when they are considered simultaneously. The evaluated data set comprises the merger of two Belgian longitudinal studies, BELSTRESS III and SOMSTRESS. It includes 3821 workers (1541 men) aged 21-66 years, employed in eight organizations. A multiple mediation analysis was performed to explain the higher prevalence among women. Estimated factors were occupational grade, total number of paid working hours per week, job strain, overcommitment, home-work interference and social support at and outside work. Prospective data concerning duration and frequency of medically justified sickness absence (registered by the organizations) were used as outcomes. Overall, the mediating factors partially account for gender difference in sickness absence. The strongest mediator for both outcomes is job strain. In addition, difference in absence duration is mediated by social support at work, whereas difference in frequency is mediated by professional grade and home-work interference. Our results call attention to the necessity to elaborate actual preventive actions aiming at favouring a better positioning of women on the labour market in term of hierarchical level as well as in terms of quality of work for reducing sickness absence in this group.

College Alcohol Beliefs and Drinking Consequences: A Multiple Mediation Analysis of Norms, Expectancies, and Willingness to Experience Drinking Consequences

ERIC Educational Resources Information Center

Osberg, Timothy M.; Boyer, Amber

2018-01-01

Objective: We explored the potential mediating role of willingness to experience drinking consequences and other traditional alcohol outcome predictors (descriptive norms, injunctive norms, positive alcohol expectancies) in explaining the association between college alcohol beliefs1 (CABs) and the actual experience of drinking consequences among…

Causal relationship between the AHSG gene and BMD through fetuin-A and BMI: multiple mediation analysis.

PubMed

Sritara, C; Thakkinstian, A; Ongphiphadhanakul, B; Chailurkit, L; Chanprasertyothin, S; Ratanachaiwong, W; Vathesatogkit, P; Sritara, P

2014-05-01

Using mediation analysis, a causal relationship between the AHSG gene and bone mineral density (BMD) through fetuin-A and body mass index (BMI) mediators was suggested. Fetuin-A, a multifunctional protein of hepatic origin, is associated with bone mineral density. It is unclear if this association is causal. This study aimed at clarification of this issue. A cross-sectional study was conducted among 1,741 healthy workers from the Electricity Generating Authority of Thailand (EGAT) cohort. The alpha-2-Heremans-Schmid glycoprotein (AHSG) rs2248690 gene was genotyped. Three mediation models were constructed using seemingly unrelated regression analysis. First, the ln[fetuin-A] group was regressed on the AHSG gene. Second, the BMI group was regressed on the AHSG gene and the ln[fetuin-A] group. Finally, the BMD model was constructed by fitting BMD on two mediators (ln[fetuin-A] and BMI) and the independent AHSG variable. All three analyses were adjusted for confounders. The prevalence of the minor T allele for the AHSG locus was 15.2%. The AHSG locus was highly related to serum fetuin-A levels (P < 0.001). Multiple mediation analyses showed that AHSG was significantly associated with BMD through the ln[fetuin-A] and BMI pathway, with beta coefficients of 0.0060 (95% CI 0.0038, 0.0083) and 0.0030 (95% CI 0.0020, 0.0045) at the total hip and lumbar spine, respectively. About 27.3 and 26.0% of total genetic effects on hip and spine BMD, respectively, were explained by the mediation effects of fetuin-A and BMI. Our study suggested evidence of a causal relationship between the AHSG gene and BMD through fetuin-A and BMI mediators.

Studies of transformational leadership in consumer service: market orientation behavior and alternative roles for the mediators and moderators of change commitment.

PubMed

Yang, Yi-Feng

2013-12-01

The present paper evaluates the relation between transformational leadership and market orientation along with the mediating and moderating effects of change commitment for employees in customer centers in Taiwan. 327 questionnaires were returned by personnel at several customer centers in four different insurance companies. Inter-rater agreement was acceptable based on the multiple raters (i.e., the consumer-related employees from the division groups) of one individual (i.e., a manager)--indicating the aggregated measures were acceptable. The multi-source sample comprised data taken from the four division centers: phone services, customer representatives, financial specialists, and front-line salespeople. The relations were assessed using a multiple mediation procedure incorporating bootstrap techniques and PRODCLIN2 with structural equation modeling analysis. The results reflect a mediating role for change commitment.

Education and health and well-being: direct and indirect effects with multiple mediators and interactions with multiple imputed data in Stata.

PubMed

Sheikh, Mashhood Ahmed; Abelsen, Birgit; Olsen, Jan Abel

2017-11-01

Previous methods for assessing mediation assume no multiplicative interactions. The inverse odds weighting (IOW) approach has been presented as a method that can be used even when interactions exist. The substantive aim of this study was to assess the indirect effect of education on health and well-being via four indicators of adult socioeconomic status (SES): income, management position, occupational hierarchy position and subjective social status. 8516 men and women from the Tromsø Study (Norway) were followed for 17 years. Education was measured at age 25-74 years, while SES and health and well-being were measured at age 42-91 years. Natural direct and indirect effects (NIE) were estimated using weighted Poisson regression models with IOW. Stata code is provided that makes it easy to assess mediation in any multiple imputed dataset with multiple mediators and interactions. Low education was associated with lower SES. Consequently, low SES was associated with being unhealthy and having a low level of well-being. The effect (NIE) of education on health and well-being is mediated by income, management position, occupational hierarchy position and subjective social status. This study contributes to the literature on mediation analysis, as well as the literature on the importance of education for health-related quality of life and subjective well-being. The influence of education on health and well-being had different pathways in this Norwegian sample. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Disease-specific molecular events in cortical multiple sclerosis lesions

PubMed Central

Wimmer, Isabella; Höftberger, Romana; Gerlach, Susanna; Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Mahad, Don; Binder, Christoph J.; Krumbholz, Markus; Bauer, Jan; Bradl, Monika

2013-01-01

Cortical lesions constitute an important part of multiple sclerosis pathology. Although inflammation appears to play a role in their formation, the mechanisms leading to demyelination and neurodegeneration are poorly understood. We aimed to identify some of these mechanisms by combining gene expression studies with neuropathological analysis. In our study, we showed that the combination of inflammation, plaque-like primary demyelination and neurodegeneration in the cortex is specific for multiple sclerosis and is not seen in other chronic inflammatory diseases mediated by CD8-positive T cells (Rasmussen’s encephalitis), B cells (B cell lymphoma) or complex chronic inflammation (tuberculous meningitis, luetic meningitis or chronic purulent meningitis). In addition, we performed genome-wide microarray analysis comparing micro-dissected active cortical multiple sclerosis lesions with those of tuberculous meningitis (inflammatory control), Alzheimer’s disease (neurodegenerative control) and with cortices of age-matched controls. More than 80% of the identified multiple sclerosis-specific genes were related to T cell-mediated inflammation, microglia activation, oxidative injury, DNA damage and repair, remyelination and regenerative processes. Finally, we confirmed by immunohistochemistry that oxidative damage in cortical multiple sclerosis lesions is associated with oligodendrocyte and neuronal injury, the latter also affecting axons and dendrites. Our study provides new insights into the complex mechanisms of neurodegeneration and regeneration in the cortex of patients with multiple sclerosis. PMID:23687122

Method for evaluating multiple mediators: mediating effects of smoking and COPD on the association between the CHRNA5-A3 variant and lung cancer risk.

PubMed

Wang, Jian; Spitz, Margaret R; Amos, Christopher I; Wu, Xifeng; Wetter, David W; Cinciripini, Paul M; Shete, Sanjay

2012-01-01

A mediation model explores the direct and indirect effects between an independent variable and a dependent variable by including other variables (or mediators). Mediation analysis has recently been used to dissect the direct and indirect effects of genetic variants on complex diseases using case-control studies. However, bias could arise in the estimations of the genetic variant-mediator association because the presence or absence of the mediator in the study samples is not sampled following the principles of case-control study design. In this case, the mediation analysis using data from case-control studies might lead to biased estimates of coefficients and indirect effects. In this article, we investigated a multiple-mediation model involving a three-path mediating effect through two mediators using case-control study data. We propose an approach to correct bias in coefficients and provide accurate estimates of the specific indirect effects. Our approach can also be used when the original case-control study is frequency matched on one of the mediators. We employed bootstrapping to assess the significance of indirect effects. We conducted simulation studies to investigate the performance of the proposed approach, and showed that it provides more accurate estimates of the indirect effects as well as the percent mediated than standard regressions. We then applied this approach to study the mediating effects of both smoking and chronic obstructive pulmonary disease (COPD) on the association between the CHRNA5-A3 gene locus and lung cancer risk using data from a lung cancer case-control study. The results showed that the genetic variant influences lung cancer risk indirectly through all three different pathways. The percent of genetic association mediated was 18.3% through smoking alone, 30.2% through COPD alone, and 20.6% through the path including both smoking and COPD, and the total genetic variant-lung cancer association explained by the two mediators was 69.1%.

Neuropsychological performance measures as intermediate phenotypes for attention-deficit/hyperactivity disorder: A multiple mediation analysis

PubMed Central

KAMRADT, JACLYN M.; NIGG, JOEL T.; FRIDERICI, KAREN H.; NIKOLAS, MOLLY A.

2016-01-01

Genetic influences on dopaminergic neurotransmission have been implicated in attention-deficit hyperactivity disorder (ADHD) and are theorized to impact cognitive functioning via alterations in frontal–striatal circuitry. Neuropsychological functioning has been proposed to account for the potential associations between dopamine candidate genes and ADHD. However, to date, this mediation hypothesis has not been directly tested. Participants were 498 youth ages 6–17 years (mean M = 10.8 years, SD = 2.4 years, 55.0% male). All youth completed a multistage, multiple-informant assessment procedure to identify ADHD and non-ADHD cases, as well as a comprehensive neuropsychological battery. Youth provided a saliva sample for DNA analyses; the 480 base pair variable number of tandem repeat polymorphism of the dopamine active transporter 1 gene (DAT1) and the 120 base pair promoter polymorphism of the dopamine receptor D4 gene (DRD4) were genotyped. Multiple mediation analysis revealed significant indirect associations between DAT1 genotype and inattention, hyperactivity–impulsivity, and oppositionality, with specific indirect effects through response inhibition. The results highlight the role of neurocognitive task performance, particularly response inhibition, as a potential intermediate phenotype for ADHD, further elucidating the relationship between genetic polymorphisms and externalizing psychopathology. PMID:27049476

Are socioeconomic disparities in health behavior mediated by differential media use? Test of the communication inequality theory.

PubMed

Ishikawa, Yoshiki; Kondo, Naoki; Kawachi, Ichiro; Viswanath, Kasisomayajula

2016-11-01

Communication inequality has been offered as one potential mechanism through which social determinants influence multiple health behaviors. The purpose of this study was to examine the underlying mechanisms between communication inequality and health behaviors. Data from a nationally representative cross-sectional survey of 18,426 people aged 18 years and above in the United States were used for secondary analysis. Measures included socio-demographic characteristics, social participation (structural social capital), health media use (TV, print, and the Internet), and five health behaviors (physical activity, cigarette smoking, alcohol use, and intake of fruit and vegetable). Path analysis was performed to examine the linkages between social determinants, health media use, social participation, and social gradients in health behaviors. Path analysis revealed that socioeconomic gradients in health behaviors is mediated by: 1) inequalities in health media use; 2) disparities in social participation, which leads to differential media use; and 3) disparities in social participation that are not mediated by media use. Consistent with the theory of communication inequality, socioeconomic disparities in media use partially mediate disparities in multiple health behaviors. To address health inequalities, it is important to utilize health media to target populations with low socioeconomic statuses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Core Self-Evaluations as a Mediator between Functional Disability and Life Satisfaction in College Students with Disabilities Majoring in Science and Technology

ERIC Educational Resources Information Center

Smedema, Susan Miller; Pfaller, Joseph S.; Yaghmaian, Rana A.; Weaver, Hayley; da Silva Cardoso, Elizabeth; Chan, Fong

2015-01-01

Purpose: To examine the mediational effect of core self-evaluations (CSE) on the relationship between functional disability and life satisfaction. Methods: A quantitative descriptive design using multiple regression analysis. The participants were 97 college students with disabilities receiving services through Hunter College's Minority-Disability…

Affective and Cognitive Empathy as Mediators of Gender Differences in Cyber and Traditional Bullying

ERIC Educational Resources Information Center

Topcu, Cigdem; Erdur-Baker, Ozgur

2012-01-01

Gender differences in bullying behavior among adolescents have been observed, but the reasons for the discrepancy in males' and females' bullying experiences has been the focus of few studies. This study examined the role of the cognitive and affective empathy in explaining gender differences in bullying through multiple mediation analysis. The…

Perceived social support and early adolescents' achievement: the mediational roles of motivational beliefs and emotions.

PubMed

Ahmed, Wondimu; Minnaert, Alexander; van der Werf, Greetje; Kuyper, Hans

2010-01-01

Although a bulk of literature shows that perceived social support (PSS) influences academic achievement, the mechanisms through which this effect operates received little empirical attention. The present study examined the multiple mediational effects of motivational beliefs (competence beliefs and subjective value) and emotions (anxiety and enjoyment) that may account for the empirical link between PSS (from parents, peers and teachers) and mathematics achievement. The participants of the study were 238 grade 7 students (average age = 13.2 years, girls = 54%, predominantly native Dutch middle class socioeconomic status). A bootstrap analysis (a relatively new technique for testing multiple mediation) revealed that the motivational beliefs and the emotions, jointly, partially mediated the effect of PSS on achievement. The proportion of the effects mediated, however, varied across the support sources from 55% to 75%. The findings lend support to the theoretical assumptions in the literature that supportive social relationships influence achievement through motivational and affective pathways.

Parent involvement and student academic performance: a multiple mediational analysis.

PubMed

Topor, David R; Keane, Susan P; Shelton, Terri L; Calkins, Susan D

2010-01-01

Parent involvement in a child's education is consistently found to be positively associated with a child's academic performance. However, there has been little investigation of the mechanisms that explain this association. The present study examines two potential mechanisms of this association: the child's perception of cognitive competence and the quality of the student-teacher relationship. This study used a sample of 158 seven-year-old participants, their mothers, and their teachers. Results indicated a statistically significant association between parent involvement and a child's academic performance, over and above the impact of the child's intelligence. A multiple mediation model indicated that the child's perception of cognitive competence fully mediated the relation between parent involvement and the child's performance on a standardized achievement test. The quality of the student-teacher relationship fully mediated the relation between parent involvement and teacher ratings of the child's classroom academic performance. Limitations, future research directions, and implications for public policy initiatives are discussed.

War-related trauma exposure and multiple risk behaviors among school-going adolescents in Northern Uganda: the mediating role of depression symptoms.

PubMed

Okello, James; Nakimuli-Mpungu, Etheldreda; Musisi, Seggane; Broekaert, Eric; Derluyn, Ilse

2013-11-01

The relationship between war-related trauma exposure, depressive symptoms and multiple risk behaviors among adolescents is less clear in sub-Saharan Africa. We analyzed data collected from a sample of school-going adolescents four years postwar. Participants completed interviews assessing various risk behaviors defined by the Youth Self Report (YSR) and a sexual risk behavior survey, and were screened for post-traumatic stress, anxiety and depression symptoms based on the Impact of Events Scale Revised (IESR) and Hopkins Symptom Checklist for Adolescents (HSCL-37A) respectively. Multivariate logistic regression was used to assess factors independently associated with multiple risk behaviors. The logistic regression model of Baron and Kenny (1986) was used to evaluate the mediating role of depression in the relationship between stressful war events and multiple risk behaviors. Of 551 participants, 139 (25%) reported multiple (three or more) risk behaviors in the past year. In the multivariate analyses, depression symptoms remained uniquely associated with multiple risk behavior after adjusting for potential confounders including socio-demographic characteristics, war-related trauma exposure variables, anxiety and post-traumatic stress symptoms. In mediation analysis, depression symptoms mediated the associations between stressful war events and multiple risk behaviors. The psychometric properties of the questionnaires used in this study are not well established in war affected African samples thus ethno cultural variation may decrease the validity of our measures. Adolescents with depression may be at a greater risk of increased engagement in multiple risk behaviors. Culturally sensitive and integrated interventions to treat and prevent depression among adolescents in post-conflict settings are urgently needed. © 2013 Elsevier B.V. All rights reserved.

Pathways between Socioeconomic Disadvantage and Childhood Growth in the Scottish Longitudinal Study, 1991-2001.

PubMed

Silverwood, Richard J; Williamson, Lee; Grundy, Emily M; De Stavola, Bianca L

2016-01-01

Socioeconomically disadvantaged children are more likely to be of shorter stature and overweight, leading to greater risk of obesity in adulthood. Disentangling the mediatory pathways between socioeconomic disadvantage and childhood size may help in the development of appropriate policies aimed at reducing these health inequalities. We aimed to elucidate the putative mediatory role of birth weight using a representative sample of the Scottish population born 1991-2001 (n = 16,628). Estimated height and overweight/obesity at age 4.5 years were related to three measures of socioeconomic disadvantage (mother's education, Scottish Index of Multiple Deprivation, synthetic weekly income). Mediation was examined using two approaches: a 'traditional' mediation analysis and a counterfactual-based mediation analysis. Both analyses identified a negative effect of each measure of socioeconomic disadvantage on height, mediated to some extent by birth weight, and a positive 'direct effect' of mother's education and Scottish Index of Multiple Deprivation on overweight/obesity, which was partly counterbalanced by a negative 'indirect effect'. The extent of mediation estimated when adopting the traditional approach was greater than when adopting the counterfactual-based approach because of inappropriate handling of intermediate confounding in the former. Our findings suggest that higher birth weight in more disadvantaged groups is associated with reduced social inequalities in height but also with increased inequalities in overweight/obesity.

Patient-provider relationship as mediator between adult attachment and self-management in primary care patients with multiple chronic conditions.

PubMed

Brenk-Franz, Katja; Strauß, Bernhard; Tiesler, Fabian; Fleischhauer, Christian; Schneider, Nico; Gensichen, Jochen

2017-06-01

The conceptual model of attachment theory has been applied to understand the predispositions of patients in medical care and the patient-provider relationship. In patients with chronic conditions insecure attachment was connected to poorer self-management. The patient-provider relationship is associated with a range of health related outcomes and self-management skills. We determined whether the quality of the patient-provider relationship mediates the link between adult attachment and self-management among primary care patients with multiple chronic diseases. 209 patients with a minimum of three chronic diseases (including type II diabetes, hypertension and at least one other chronic condition) between the ages of 50 and 85 from eight general practices were included in the APRICARE cohort study. Adult attachment was measured via self-report (ECR-RD), self-management skills by the FERUS and the patient-provider relationship by the PRA-D. The health status and chronicity were assessed by the GP. Multiple mediation analyses were used to examine whether aspects of the patient-provider relationship (communication, information, affectivity) are a mediators of associations between adult attachment and self-management. The analysis revealed that the quality of the patient-provider relationship mediated the effect of attachment on self-management in patients with multiple chronic conditions. Particularly the quality of communication and information over the course of treatment has a significant mediating influence. A personalized, attachment-related approach that promotes active patient-provider communication and gives information about the treatment to the patient may improve self-management skills in patients. Copyright © 2017 Elsevier Inc. All rights reserved.

A Bifactor Approach to Model Multifaceted Constructs in Statistical Mediation Analysis.

PubMed

Gonzalez, Oscar; MacKinnon, David P

Statistical mediation analysis allows researchers to identify the most important mediating constructs in the causal process studied. Identifying specific mediators is especially relevant when the hypothesized mediating construct consists of multiple related facets. The general definition of the construct and its facets might relate differently to an outcome. However, current methods do not allow researchers to study the relationships between general and specific aspects of a construct to an outcome simultaneously. This study proposes a bifactor measurement model for the mediating construct as a way to parse variance and represent the general aspect and specific facets of a construct simultaneously. Monte Carlo simulation results are presented to help determine the properties of mediated effect estimation when the mediator has a bifactor structure and a specific facet of a construct is the true mediator. This study also investigates the conditions when researchers can detect the mediated effect when the multidimensionality of the mediator is ignored and treated as unidimensional. Simulation results indicated that the mediation model with a bifactor mediator measurement model had unbiased and adequate power to detect the mediated effect with a sample size greater than 500 and medium a - and b -paths. Also, results indicate that parameter bias and detection of the mediated effect in both the data-generating model and the misspecified model varies as a function of the amount of facet variance represented in the mediation model. This study contributes to the largely unexplored area of measurement issues in statistical mediation analysis.

[Body image dissatisfaction as a mediator of the association between BMI, self-esteem and mental health in early adolescents: a multiple-group path analysis across gender].

PubMed

Jang, Mi Heui; Lee, Gyungjoo

2013-04-01

This study was done to examine not only the relationships between body mass index (BMI), self-esteem, body image dissatisfaction (BID) and mental health, according to gender, but the mediating role of BID on mental health in relation to BMI and self-esteem among early adolescents. Data from 576 (296 boys and 280 girls) elementary school students in grades 5 to 6 were collected. A multiple-group path analysis was utilized to examine the relationships between BMI, self-esteem, BID and mental health by gender. In the path analysis for all students, poor mental health was related directly to BID, while it was indirectly related to BMI and self-esteem. In the multiple-group path analysis of both genders, BID was found to have a significant direct and indirect effect on mental health for girls alone. The findings suggested that BID should be examined early to prevent poor mental health in early adolescent girls. This study helps to elucidate the role of early adolescent BID on mental health and provides insight for further prevention and intervention programs in school and community mental health settings.

Multiple dimensions of spirituality in recovery: a lagged mediational analysis of Alcoholics Anonymous' principal theoretical mechanism of behavior change.

PubMed

Krentzman, Amy R; Cranford, James A; Robinson, Elizabeth A R

2013-01-01

Alcoholics Anonymous (AA) states that recovery is possible through spiritual experiences and spiritual awakenings. Research examining spirituality as a mediator of AA's effect on drinking has been mixed. It is unknown whether such findings are due to variations in the operationalization of key constructs, such as AA and spirituality. To answer these questions, the authors used a longitudinal model to test 2 dimensions of AA as focal predictors and 6 dimensions of spirituality as possible mediators of AA's association with drinking. Data from the first 18 months of a 3-year longitudinal study of 364 alcohol-dependent individuals were analyzed. Structural equation modeling was used to replicate the analyses of Kelly et al. (Alcohol Clin Exp Res. 2011;35:454-463) and to compare AA attendance and AA involvement as focal predictors. Multiple regression analyses were used to determine which spirituality dimensions changed as the result of AA participation. A trimmed, data-driven model was employed to test multiple mediation paths simultaneously. The findings of the Kelly et al. study were replicated. AA involvement was a stronger predictor of drinking outcomes than AA attendance. AA involvement predicted increases in private religious practices, daily spiritual experiences, and forgiveness of others. However, only private religious practices mediated the relationship between AA and drinking.

Mindfulness facets, trait emotional intelligence, emotional distress, and multiple health behaviors: A serial two-mediator model.

PubMed

Jacobs, Ingo; Wollny, Anna; Sim, Chu-Won; Horsch, Antje

2016-06-01

In the present study, we tested a serial mindfulness facets-trait emotional intelligence (TEI)-emotional distress-multiple health behaviors mediation model in a sample of N = 427 German-speaking occupational therapists. The mindfulness facets-TEI-emotional distress section of the mediation model revealed partial mediation for the mindfulness facets Act with awareness (Act/Aware) and Accept without judgment (Accept); inconsistent mediation was found for the Describe facet. The serial two-mediator model included three mediational pathways that may link each of the four mindfulness facets with multiple health behaviors. Eight out of 12 indirect effects reached significance and fully mediated the links between Act/Aware and Describe to multiple health behaviors; partial mediation was found for Accept. The mindfulness facet Observe was most relevant for multiple health behaviors, but its relation was not amenable to mediation. Implications of the findings will be discussed. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Depression and pain: testing of serial multiple mediators.

PubMed

Wongpakaran, Tinakon; Wongpakaran, Nahathai; Tanchakvaranont, Sitthinant; Bookkamana, Putipong; Pinyopornpanish, Manee; Wannarit, Kamonporn; Satthapisit, Sirina; Nakawiro, Daochompu; Hiranyatheb, Thanita; Thongpibul, Kulvadee

2016-01-01

Despite the fact that pain is related to depression, few studies have been conducted to investigate the variables that mediate between the two conditions. In this study, the authors explored the following mediators: cognitive function, self-sacrificing interpersonal problems, and perception of stress, and the effects they had on pain symptoms among patients with depressive disorders. An analysis was performed on the data of 346 participants with unipolar depressive disorders. The 17-item Hamilton Depression Rating Scale, Mini-Mental State Examination, the pain subscale of the health-related quality of life (SF-36), the self-sacrificing subscale of the Inventory of Interpersonal Problems, and the Perceived Stress Scale were used. Parallel multiple mediator and serial multiple mediator models were used. An alternative model regarding the effect of self-sacrificing on pain was also proposed. Perceived stress, self-sacrificing interpersonal style, and cognitive function were found to significantly mediate the relationship between depression and pain, while controlling for demographic variables. The total effect of depression on pain was significant. This model, with an additional three mediators, accounted for 15% of the explained variance in pain compared to 9% without mediators. For the alternative model, after controlling for the mediators, a nonsignificant total direct effect level of self-sacrificing was found, suggesting that the effect of self-sacrificing on pain was based only on an indirect effect and that perceived stress was found to be the strongest mediator. Serial mediation may help us to see how depression and pain are linked and what the fundamental mediators are in the chain. No significant, indirect effect of self-sacrificing on pain was observed, if perceived stress was not part of the depression and/or cognitive function mediational chain. The results shown here have implications for future research, both in terms of testing the model and in clinical application.

POWER ANALYSIS FOR COMPLEX MEDIATIONAL DESIGNS USING MONTE CARLO METHODS

PubMed Central

Thoemmes, Felix; MacKinnon, David P.; Reiser, Mark R.

2013-01-01

Applied researchers often include mediation effects in applications of advanced methods such as latent variable models and linear growth curve models. Guidance on how to estimate statistical power to detect mediation for these models has not yet been addressed in the literature. We describe a general framework for power analyses for complex mediational models. The approach is based on the well known technique of generating a large number of samples in a Monte Carlo study, and estimating power as the percentage of cases in which an estimate of interest is significantly different from zero. Examples of power calculation for commonly used mediational models are provided. Power analyses for the single mediator, multiple mediators, three-path mediation, mediation with latent variables, moderated mediation, and mediation in longitudinal designs are described. Annotated sample syntax for Mplus is appended and tabled values of required sample sizes are shown for some models. PMID:23935262

Sources of sport confidence, imagery type and performance among competitive athletes: the mediating role of sports confidence.

PubMed

Levy, A R; Perry, J; Nicholls, A R; Larkin, D; Davies, J

2015-01-01

This study explored the mediating role of sport confidence upon (1) sources of sport confidence-performance relationship and (2) imagery-performance relationship. Participants were 157 competitive athletes who completed state measures of confidence level/sources, imagery type and performance within one hour after competition. Among the current sample, confirmatory factor analysis revealed appropriate support for the nine-factor SSCQ and the five-factor SIQ. Mediational analysis revealed that sport confidence had a mediating influence upon the achievement source of confidence-performance relationship. In addition, both cognitive and motivational imagery types were found to be important sources of confidence, as sport confidence mediated imagery type- performance relationship. Findings indicated that athletes who construed confidence from their own achievements and report multiple images on a more frequent basis are likely to benefit from enhanced levels of state sport confidence and subsequent performance.

Anxiety, affect, self-esteem, and stress: mediation and moderation effects on depression.

PubMed

Nima, Ali Al; Rosenberg, Patricia; Archer, Trevor; Garcia, Danilo

2013-01-01

Mediation analysis investigates whether a variable (i.e., mediator) changes in regard to an independent variable, in turn, affecting a dependent variable. Moderation analysis, on the other hand, investigates whether the statistical interaction between independent variables predict a dependent variable. Although this difference between these two types of analysis is explicit in current literature, there is still confusion with regard to the mediating and moderating effects of different variables on depression. The purpose of this study was to assess the mediating and moderating effects of anxiety, stress, positive affect, and negative affect on depression. Two hundred and two university students (males  = 93, females  = 113) completed questionnaires assessing anxiety, stress, self-esteem, positive and negative affect, and depression. Mediation and moderation analyses were conducted using techniques based on standard multiple regression and hierarchical regression analyses. The results indicated that (i) anxiety partially mediated the effects of both stress and self-esteem upon depression, (ii) that stress partially mediated the effects of anxiety and positive affect upon depression, (iii) that stress completely mediated the effects of self-esteem on depression, and (iv) that there was a significant interaction between stress and negative affect, and between positive affect and negative affect upon depression. The study highlights different research questions that can be investigated depending on whether researchers decide to use the same variables as mediators and/or moderators.

Stressors and anxiety in dementia caregiving: multiple mediation analysis of rumination, experiential avoidance, and leisure.

PubMed

Romero-Moreno, R; Losada, A; Márquez-González, M; Mausbach, B T

2016-11-01

Despite the robust associations between stressors and anxiety in dementia caregiving, there is a lack of research examining which factors contribute to explain this relationship. This study was designed to test a multiple mediation model of behavioral and psychological symptoms of dementia (BPSD) and anxiety that proposes higher levels of rumination and experiential avoidance and lower levels of leisure satisfaction as potential mediating variables. The sample consisted of 256 family caregivers. In order to test a simultaneously parallel multiple mediation model of the BPSD to anxiety pathway, a PROCESS method was used and bias-corrected and accelerated bootstrapping method was used to test confidence intervals. Higher levels of stressors significantly predicted anxiety. Greater stressors significantly predicted higher levels of rumination and experiential avoidance, and lower levels of leisure satisfaction. These three coping variables significantly predicted anxiety. Finally, rumination, experiential avoidance, and leisure satisfaction significantly mediated the link between stressors and anxiety. The explained variance for the final model was 47.09%. Significant contrasts were found between rumination and leisure satisfaction, with rumination being a significantly higher mediator. The results suggest that caregivers' experiential avoidance, rumination, and leisure satisfaction may function as mechanisms through which BPSD influence on caregivers' anxiety. Training caregivers in reducing their levels of experiential avoidance and rumination by techniques that foster their ability of acceptance of their negative internal experiences, and increase their level of leisure satisfaction, may be helpful to reduce their anxiety symptoms developed by stressors.

Parent involvement and student academic performance: A multiple mediational analysis

PubMed Central

Topor, David R.; Keane, Susan P.; Shelton, Terri L.; Calkins, Susan D.

2011-01-01

Parent involvement in a child's education is consistently found to be positively associated with a child's academic performance. However, there has been little investigation of the mechanisms that explain this association. The present study examines two potential mechanisms of this association: the child's perception of cognitive competence and the quality of the student-teacher relationship. This study used a sample of 158 seven-year old participants, their mothers, and their teachers. Results indicated a statistically significant association between parent involvement and a child's academic performance, over and above the impact of the child's intelligence. A multiple mediation model indicated that the child's perception of cognitive competence fully mediated the relation between parent involvement and the child's performance on a standardized achievement test. The quality of the student-teacher relationship fully mediated the relation between parent involvement and teacher ratings of the child's classroom academic performance. Limitations, future research directions, and implications for public policy initiatives were discussed. PMID:20603757

Evaluation of a Multiple Mediator Model of the Relationship between Core Self-Evaluations and Job Satisfaction in Employed Individuals with Disabilities

ERIC Educational Resources Information Center

Smedema, Susan Miller; Kesselmayer, Rachel Friefeld; Peterson, Lauren

2018-01-01

Purpose: To test a meditation model of the relationship between core self-evaluations (CSE) and job satisfaction in employed individuals with disabilities. Method: A quantitative descriptive design using Hayes's (2012) PROCESS macro for SPSS and multiple regression analysis. Two-hundred fifty-nine employed persons with disabilities were recruited…

How information about overdetection changes breast cancer screening decisions: a mediation analysis within a randomised controlled trial.

PubMed

Hersch, Jolyn; McGeechan, Kevin; Barratt, Alexandra; Jansen, Jesse; Irwig, Les; Jacklyn, Gemma; Houssami, Nehmat; Dhillon, Haryana; McCaffery, Kirsten

2017-10-06

In a randomised controlled trial, we found that informing women about overdetection changed their breast screening decisions. We now present a mediation analysis exploring the psychological pathways through which study participants who received the intervention processed information about overdetection and how this influenced their decision-making. We examined a series of potential mediators in the causal chain between exposure to overdetection information and women's subsequently reported breast screening intentions. Serial multiple mediation analysis within a randomised controlled trial. New South Wales, Australia. 811 women aged 48-50 years with no personal history of breast cancer. Two versions of a decision aid giving women information about breast cancer deaths averted and false positives from mammography screening, either with (intervention) or without (control) information on overdetection. Intentions to undergo breast cancer screening in the next 2-3 years. Knowledge about overdetection, worry about breast cancer, attitudes towards breast screening and anticipated regret. The effect of information about overdetection on women's breast screening intentions was mediated through multiple cognitive and affective processes. In particular, the information led to substantial improvements in women's understanding of overdetection, and it influenced-both directly and indirectly via its effect on knowledge-their attitudes towards having screening. Mediation analysis showed that the mechanisms involving knowledge and attitudes were particularly important in determining women's intentions about screening participation. Even in this emotive context, new information influenced women's decision-making by changing their understanding of possible consequences of screening and their attitudes towards undergoing it. These findings emphasise the need to provide good-quality information on screening outcomes and to communicate this information effectively, so that women can make well-informed decisions. This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613001035718) on 17 September 2013. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Multiple Traumas, Maternal Depression, Mother-Child Relationship, Social Support, and Young Children's Behavioral Problems.

PubMed

Schiff, Miriam; Pat-Horenczyk, Ruth; Ziv, Yuval; Brom, Danny

2017-09-01

This study examined whether maternal depression, mother-child relationships, and maternal perceived social support mediate the associations between child's exposure to multiple traumatic events and behavioral problems. We recruited a representative sample of 904 Israeli (Jewish and Arab) mothers and their 2- to 6-year-old children. Data collection was conducted through structured face-to-face interviews with the mothers between July and November 2011. All measures were completed by the mothers. We used the child's and mother's exposure to political violence questionnaires, Child Behavior Checklist (CBCL), a short version of the Parental Acceptance-Rejection Questionnaire (PARQ), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Medical Outcomes Study (MOS) Social Support Survey. The research study model was tested using path analysis. The model showed a very good fit to the data, suggesting that maternal rejection, maternal depression, and social support play an important role in child's behavioral problems in the context of multiple traumatic events. Higher levels of maternal rejection were significantly associated with greater children behavior problems. Maternal rejection mediated the associations between maternal depressive symptoms and child's behavioral problems. Maternal perceived social support mediated the associations between child's exposure to multiple traumatic events and child's behavioral problems; child's exposure to multiple traumatic events was associated with lower levels of maternal perceived social support. In turn, lower levels of perceived social support were associated with higher levels of behavioral problems. In conclusion, in accordance with the "social stress framework," social support has a mediation role in the association between exposure to traumatic events and child's behavioral problems. Thus, enhancing social support to mothers to young children in the context of multiple traumatic events is essential for children resiliency.

Associations of Thalassemia Major and satisfaction with quality of life: The mediating effect of social support

PubMed Central

Platania, Silvia; Gruttadauria, Stefania; Citelli, Giulia; Giambrone, Loris; Di Nuovo, Santo

2017-01-01

The present research analyzed the elements of thalassemia which affect the patient’s perceived quality of life. Three hundred patients with Thalassemia Major (males = 165, 55%; females = 135, 45%; Mage = 36.13, standard deviation = 8.54) were the sample. Analysis of multiple mediations revealed a direct effect of self-efficacy on the Satisfaction with Life Scale that is mediated only by social support.The findings suggest a need to accentuate help and support to patients with Thalassemia Major. PMID:29379628

Team Performance Improvement: Mediating Roles of Employee Job Autonomy and Quality of Team Leader-Member Relations in Supportive Organizations in the Korean Business Context

ERIC Educational Resources Information Center

Song, Ji Hoon

2011-01-01

The purpose of this research was to examine the mediating roles of job autonomy and the quality of the leader-member relationship to explain the impact of organizational support on team performance. A total of 228 cases collected from Korean business organizations were used for data analysis. Hierarchical multiple regression, Type 1 SS-based…

Activator Gcn4 employs multiple segments of Med15/Gal11, including the KIX domain, to recruit mediator to target genes in vivo.

PubMed

Jedidi, Iness; Zhang, Fan; Qiu, Hongfang; Stahl, Stephen J; Palmer, Ira; Kaufman, Joshua D; Nadaud, Philippe S; Mukherjee, Sujoy; Wingfield, Paul T; Jaroniec, Christopher P; Hinnebusch, Alan G

2010-01-22

Mediator is a multisubunit coactivator required for initiation by RNA polymerase II. The Mediator tail subdomain, containing Med15/Gal11, is a target of the activator Gcn4 in vivo, critical for recruitment of native Mediator or the Mediator tail subdomain present in sin4Delta cells. Although several Gal11 segments were previously shown to bind Gcn4 in vitro, the importance of these interactions for recruitment of Mediator and transcriptional activation by Gcn4 in cells was unknown. We show that interaction of Gcn4 with the Mediator tail in vitro and recruitment of this subcomplex and intact Mediator to the ARG1 promoter in vivo involve additive contributions from three different segments in the N terminus of Gal11. These include the KIX domain, which is a critical target of other activators, and a region that shares a conserved motif (B-box) with mammalian coactivator SRC-1, and we establish that B-box is a critical determinant of Mediator recruitment by Gcn4. We further demonstrate that Gcn4 binds to the Gal11 KIX domain directly and, by NMR chemical shift analysis combined with mutational studies, we identify the likely binding site for Gcn4 on the KIX surface. Gcn4 is distinctive in relying on comparable contributions from multiple segments of Gal11 for efficient recruitment of Mediator in vivo.

The mediating effect of calling on the relationship between medical school students' academic burnout and empathy.

PubMed

Chae, Su Jin; Jeong, So Mi; Chung, Yoon-Sok

2017-09-01

This study is aimed at identifying the relationships between medical school students' academic burnout, empathy, and calling, and determining whether their calling has a mediating effect on the relationship between academic burnout and empathy. A mixed method study was conducted. One hundred twenty-seven medical students completed a survey. Scales measuring academic burnout, medical students' empathy, and calling were utilized. For statistical analysis, correlation analysis, descriptive statistics analysis, and hierarchical multiple regression analyses were conducted. For qualitative approach, eight medical students participated in a focus group interview. The study found that empathy has a statistically significant, negative correlation with academic burnout, while having a significant, positive correlation with calling. Sense of calling proved to be an effective mediator of the relationship between academic burnout and empathy. This result demonstrates that calling is a key variable that mediates the relationship between medical students' academic burnout and empathy. As such, this study provides baseline data for an education that could improve medical students' empathy skills.

Strength and cardiometabolic risk in young adults: The mediator role of aerobic fitness and waist circumference.

PubMed

Díez-Fernández, A; Martínez-Vizcaíno, V; Torres-Costoso, A; Cañete García-Prieto, J; Franquelo-Morales, P; Sánchez-López, M

2018-07-01

The aim of this study was to analyze the mediation role of cardiorespiratory fitness and waist circumference in the association between muscular strength and cardiometabolic risk. A cross-sectional study involved first-year college students (n = 370) from a Spanish public university was performed. We measured weight, height, waist circumference, blood pressure, biochemical variables, maximum handgrip strength assessment, and cardiorespiratory fitness. We calculated handgrip dynamometry/weight and a previously validated cardiometabolic risk index. Analysis of covariance models was conducted to test differences in cardiometabolic risk values across muscular strength, cardiorespiratory fitness, and waist circumference categories, controlling for confounders. Hayes' PROCESS macro was used for the multiple mediation analysis. The relationship between muscular strength and cardiometabolic risk did not remain significant (c' = 1.76 [1.4]; P > .05) in a multiple serial bootstrapped mediation model including cardiorespiratory fitness and waist circumference as mediators when controlling for age and sex. According to the indirect effect, the significant paths in the model mediating this relationship between muscular strength and cardiometabolic risk index were as follows: muscular strength → waist circumference → cardiometabolic risk index (-4.899; 95% CI: -6.690; -3.450) and muscular strength → cardiorespiratory fitness → waist circumference → cardiometabolic risk index (-0.720; 95% CI: -1.316; -0.360). Both cardiorespiratory fitness and waist circumference mediate the association between muscular strength and cardiometabolic risk in young adults. Thus, our results place cardiorespiratory fitness and waist circumference as the main targets of physical activity programmes aimed at preventing cardiometabolic diseases. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acid-growth response and alpha-expansins in suspension cultures of bright yellow 2 tobacco

NASA Technical Reports Server (NTRS)

Link, B. M.; Cosgrove, D. J.

1998-01-01

The possibility that Bright Yellow 2 (BY2) tobacco (Nicotiana tabacum L.) suspension-cultured cells possess an expansin-mediated acid-growth mechanism was examined by multiple approaches. BY2 cells grew three times faster upon treatment with fusicoccin, which induces an acidification of the cell wall. Exogenous expansins likewise stimulated BY2 cell growth 3-fold. Protein extracted from BY2 cell walls possessed the expansin-like ability to induce extension of isolated walls. In western-blot analysis of BY2 wall protein, one band of 29 kD was recognized by anti-expansin antibody. Six different classes of alpha-expansin mRNA were identified in a BY2 cDNA library. Northern-blot analysis indicated moderate to low abundance of multiple alpha-expansin mRNAs in BY2 cells. From these results we conclude that BY2 suspension-cultured cells have the necessary components for expansin-mediated cell wall enlargement.

Brain mediators of the effects of noxious heat on pain

PubMed Central

Atlas, Lauren Y.; Lindquist, Martin A.; Bolger, Niall; Wager, Tor D.

2014-01-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. While useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this paper, we used multi-level mediation analysis to identify brain mediators of pain—regions whose trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across four levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including: a) somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and b) two networks co-localized with ‘default mode’ regions in which stimulus intensity-related decreases mediated increased pain. We also identified ‘thermosensory’ regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. PMID:24845572

Mediator phosphorylation prevents stress response transcription during non-stress conditions.

PubMed

Miller, Christian; Matic, Ivan; Maier, Kerstin C; Schwalb, Björn; Roether, Susanne; Strässer, Katja; Tresch, Achim; Mann, Matthias; Cramer, Patrick

2012-12-28

The multiprotein complex Mediator is a coactivator of RNA polymerase (Pol) II transcription that is required for the regulated expression of protein-coding genes. Mediator serves as an end point of signaling pathways and regulates Pol II transcription, but the mechanisms it uses are not well understood. Here, we used mass spectrometry and dynamic transcriptome analysis to investigate a functional role of Mediator phosphorylation in gene expression. Affinity purification and mass spectrometry revealed that Mediator from the yeast Saccharomyces cerevisiae is phosphorylated at multiple sites of 17 of its 25 subunits. Mediator phosphorylation levels change upon an external stimulus set by exposure of cells to high salt concentrations. Phosphorylated sites in the Mediator tail subunit Med15 are required for suppression of stress-induced changes in gene expression under non-stress conditions. Thus dynamic and differential Mediator phosphorylation contributes to gene regulation in eukaryotic cells.

Minority stress and college persistence attitudes among African American, Asian American, and Latino students: perception of university environment as a mediator.

PubMed

Wei, Meifen; Ku, Tsun-Yao; Liao, Kelly Yu-Hsin

2011-04-01

We examined whether perception of university environment mediated the association between minority status stress and college persistence attitudes after controlling for perceived general stress. Participants were 160 Asian American, African American, and Latino students who attended a predominantly White university. Results of a path model analysis showed that university environment was a significant mediator for the association between minority status stress and college persistence attitudes. Additionally, minority status stress was distinct from perceived general stress. Finally, the results from a multiple-group comparison indicated that the magnitude of the mediation effect was invariant across Asian American, African American, and Latino college students, thus supporting the generalizability of the mediation model.

Covariate Measurement Error Correction Methods in Mediation Analysis with Failure Time Data

PubMed Central

Zhao, Shanshan

2014-01-01

Summary Mediation analysis is important for understanding the mechanisms whereby one variable causes changes in another. Measurement error could obscure the ability of the potential mediator to explain such changes. This paper focuses on developing correction methods for measurement error in the mediator with failure time outcomes. We consider a broad definition of measurement error, including technical error and error associated with temporal variation. The underlying model with the ‘true’ mediator is assumed to be of the Cox proportional hazards model form. The induced hazard ratio for the observed mediator no longer has a simple form independent of the baseline hazard function, due to the conditioning event. We propose a mean-variance regression calibration approach and a follow-up time regression calibration approach, to approximate the partial likelihood for the induced hazard function. Both methods demonstrate value in assessing mediation effects in simulation studies. These methods are generalized to multiple biomarkers and to both case-cohort and nested case-control sampling design. We apply these correction methods to the Women's Health Initiative hormone therapy trials to understand the mediation effect of several serum sex hormone measures on the relationship between postmenopausal hormone therapy and breast cancer risk. PMID:25139469

Covariate measurement error correction methods in mediation analysis with failure time data.

PubMed

Zhao, Shanshan; Prentice, Ross L

2014-12-01

Mediation analysis is important for understanding the mechanisms whereby one variable causes changes in another. Measurement error could obscure the ability of the potential mediator to explain such changes. This article focuses on developing correction methods for measurement error in the mediator with failure time outcomes. We consider a broad definition of measurement error, including technical error, and error associated with temporal variation. The underlying model with the "true" mediator is assumed to be of the Cox proportional hazards model form. The induced hazard ratio for the observed mediator no longer has a simple form independent of the baseline hazard function, due to the conditioning event. We propose a mean-variance regression calibration approach and a follow-up time regression calibration approach, to approximate the partial likelihood for the induced hazard function. Both methods demonstrate value in assessing mediation effects in simulation studies. These methods are generalized to multiple biomarkers and to both case-cohort and nested case-control sampling designs. We apply these correction methods to the Women's Health Initiative hormone therapy trials to understand the mediation effect of several serum sex hormone measures on the relationship between postmenopausal hormone therapy and breast cancer risk. © 2014, The International Biometric Society.

Anxiety, Affect, Self-Esteem, and Stress: Mediation and Moderation Effects on Depression

PubMed Central

Nima, Ali Al; Rosenberg, Patricia; Archer, Trevor; Garcia, Danilo

2013-01-01

Background Mediation analysis investigates whether a variable (i.e., mediator) changes in regard to an independent variable, in turn, affecting a dependent variable. Moderation analysis, on the other hand, investigates whether the statistical interaction between independent variables predict a dependent variable. Although this difference between these two types of analysis is explicit in current literature, there is still confusion with regard to the mediating and moderating effects of different variables on depression. The purpose of this study was to assess the mediating and moderating effects of anxiety, stress, positive affect, and negative affect on depression. Methods Two hundred and two university students (males  = 93, females  = 113) completed questionnaires assessing anxiety, stress, self-esteem, positive and negative affect, and depression. Mediation and moderation analyses were conducted using techniques based on standard multiple regression and hierarchical regression analyses. Main Findings The results indicated that (i) anxiety partially mediated the effects of both stress and self-esteem upon depression, (ii) that stress partially mediated the effects of anxiety and positive affect upon depression, (iii) that stress completely mediated the effects of self-esteem on depression, and (iv) that there was a significant interaction between stress and negative affect, and between positive affect and negative affect upon depression. Conclusion The study highlights different research questions that can be investigated depending on whether researchers decide to use the same variables as mediators and/or moderators. PMID:24039896

Network-directed cis-mediator analysis of normal prostate tissue expression profiles reveals downstream regulatory associations of prostate cancer susceptibility loci.

PubMed

Larson, Nicholas B; McDonnell, Shannon K; Fogarty, Zach; Larson, Melissa C; Cheville, John; Riska, Shaun; Baheti, Saurabh; Weber, Alexandra M; Nair, Asha A; Wang, Liang; O'Brien, Daniel; Davila, Jaime; Schaid, Daniel J; Thibodeau, Stephen N

2017-10-17

Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis -acting associations due to study limitations. While trans -eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans -eQTL associations are mediated by cis -regulated genes, such as transcription factors. Leveraging a data-driven gene co-expression network, we conducted a comprehensive cis -mediator analysis using RNA-Seq data from 471 normal prostate tissue samples to identify downstream regulatory associations of previously identified prostate cancer risk variants. We discovered multiple trans -eQTL associations that were significantly mediated by cis -regulated transcripts, four of which involved risk locus 17q12, proximal transcription factor HNF1B , and target trans -genes with known HNF response elements ( MIA2 , SRC , SEMA6A , KIF12 ). We additionally identified evidence of cis -acting down-regulation of MSMB via rs10993994 corresponding to reduced co-expression of NDRG1 . The majority of these cis -mediator relationships demonstrated trans -eQTL replicability in 87 prostate tissue samples from the Gene-Tissue Expression Project. These findings provide further biological context to known risk loci and outline new hypotheses for investigation into the etiology of prostate cancer.

Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models.

PubMed

Preacher, Kristopher J; Hayes, Andrew F

2008-08-01

Hypotheses involving mediation are common in the behavioral sciences. Mediation exists when a predictor affects a dependent variable indirectly through at least one intervening variable, or mediator. Methods to assess mediation involving multiple simultaneous mediators have received little attention in the methodological literature despite a clear need. We provide an overview of simple and multiple mediation and explore three approaches that can be used to investigate indirect processes, as well as methods for contrasting two or more mediators within a single model. We present an illustrative example, assessing and contrasting potential mediators of the relationship between the helpfulness of socialization agents and job satisfaction. We also provide SAS and SPSS macros, as well as Mplus and LISREL syntax, to facilitate the use of these methods in applications.

Mediation analysis of alcohol consumption, DNA methylation, and epithelial ovarian cancer.

PubMed

Wu, Dongyan; Yang, Haitao; Winham, Stacey J; Natanzon, Yanina; Koestler, Devin C; Luo, Tiane; Fridley, Brooke L; Goode, Ellen L; Zhang, Yanbo; Cui, Yuehua

2018-03-01

Epigenetic factors and consumption of alcohol, which suppresses DNA methylation, may influence the development and progression of epithelial ovarian cancer (EOC). However, there is a lack of understanding whether these factors interact to affect the EOC risk. In this study, we aimed to gain insight into this relationship by identifying leukocyte-derived DNA methylation markers acting as potential mediators of alcohol-associated EOC. We implemented a causal inference test (CIT) and the VanderWeele and Vansteelandt multiple mediator model to examine CpG sites that mediate the association between alcohol consumption and EOC risk. We modified one step of the CIT by adopting a high-dimensional inference procedure. The data were based on 196 cases and 202 age-matched controls from the Mayo Clinic Ovarian Cancer Case-Control Study. Implementation of the CIT test revealed two CpG sites (cg09358725, cg11016563), which represent potential mediators of the relationship between alcohol consumption and EOC case-control status. Implementation of the VanderWeele and Vansteelandt multiple mediator model further revealed that these two CpGs were the key mediators. Decreased methylation at both CpGs was more common in cases who drank alcohol at the time of enrollment vs. those who did not. cg11016563 resides in TRPC6 which has been previously shown to be overexpressed in EOC. These findings suggest two CpGs may serve as novel biomarkers for EOC susceptibility.

Do social support, stigma, and social problem-solving skills predict depressive symptoms in people living with HIV? A mediation analysis.

PubMed

White, Worawan; Grant, Joan S; Pryor, Erica R; Keltner, Norman L; Vance, David E; Raper, James L

2012-01-01

Social support, stigma, and social problem solving may be mediators of the relationship between sign and symptom severity and depressive symptoms in people living with HIV (PLWH). However, no published studies have examined these individual variables as mediators in PLWH. This cross-sectional, correlational study of 150 PLWH examined whether social support, stigma, and social problem solving were mediators of the relationship between HIV-related sign and symptom severity and depressive symptoms. Participants completed self-report questionnaires during their visits at two HIV outpatient clinics in the Southeastern United States. Using multiple regression analyses as a part of mediation testing, social support, stigma, and social problem solving were found to be partial mediators of the relationship between sign and symptom severity and depressive symptoms, considered individually and as a set.

Organizational justice, psychological distress, and work engagement in Japanese workers.

PubMed

Inoue, Akiomi; Kawakami, Norito; Ishizaki, Masao; Shimazu, Akihito; Tsuchiya, Masao; Tabata, Masaji; Akiyama, Miki; Kitazume, Akiko; Kuroda, Mitsuyo

2010-01-01

To investigate the cross-sectional association between organizational justice (i.e., procedural justice and interactional justice) and psychological distress or work engagement, as well as the mediating roles of other job stressors (i.e., job demands and job control, or their combination, effort-reward imbalance [ERI], and worksite support). A total of 243 workers (185 males and 58 females) from a manufacturing factory in Japan were surveyed using a self-administered questionnaire including the Organizational Justice Questionnaire, Job Content Questionnaire, Effort-Reward Imbalance Questionnaire, K6 scale, Utrecht Work Engagement Scale, and other covariates. Multiple mediation analyses with the bootstrap technique were conducted. In the bivariate analysis, procedural justice and interactional justice were significantly and negatively associated with psychological distress; they were significantly and positively associated with work engagement. In the mediation analysis, reward at work (or ERI) significantly mediated between procedural justice or interactional justice and psychological distress; worksite support significantly mediated between procedural justice or interactional justice and work engagement. The effects of organizational justice on psychological distress seem to be mediated by reward at work (or ERI) while those regarding work engagement may be mediated by worksite support to a large extent, at least in Japanese workers.

Stigmatizing Reactions to Intimate Partner Violence Disclosure and Depression: Examining the Mediating Role of Coping Strategies

PubMed Central

Overstreet, Nicole M.; Willie, Tiara C.; Sullivan, Tami P.

2017-01-01

Objective Despite increased attention to the relation between negative social reactions to intimate partner violence (IPV) disclosure and poorer mental health outcomes for victims, research has yet to examine whether certain types of negative social reactions are associated with poorer mental health outcomes more so than others. Further, research is scarce on potential mediators of this relationship. To fill these gaps, the current study examines whether stigmatizing reactions to IPV disclosure, such as victim-blaming responses and minimizing experiences of IPV, are a specific type of negative social reaction that exerts greater influence on women’s depressive symptoms than general negative reactions, such as being angry at the perpetrators of IPV. We also examine avoidance coping as a key mediator of this relationship. Methods A cross sectional correlational study was conducted to examine these relationships. Participants were 212 women from an urban northeast community who indicated being physically victimized by their male partner in the past six months. Results Findings from a multiple regression analysis showed that stigmatizing reactions, not general negative reactions, predicted women’s depressive symptoms. In addition, a multiple mediation analysis revealed that avoidance coping strategies, but not approach coping strategies, significantly accounted for the relationship between stigmatizing social reactions and women’s depressive symptoms. Conclusions Findings have implications for improving support from informal and formal sources and subsequently, IPV exposed women’s psychological well-being. PMID:27296052

Brain mediators of the effects of noxious heat on pain.

PubMed

Atlas, Lauren Y; Lindquist, Martin A; Bolger, Niall; Wager, Tor D

2014-08-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. Although useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this study, we used multi-level mediation analysis to identify brain mediators of pain--regions in which trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across 4 levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including the following: somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and 2 networks co-localized with "default mode" regions in which stimulus intensity-related decreases mediated increased pain. We also identified "thermosensory" regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Two-condition within-participant statistical mediation analysis: A path-analytic framework.

PubMed

Montoya, Amanda K; Hayes, Andrew F

2017-03-01

Researchers interested in testing mediation often use designs where participants are measured on a dependent variable Y and a mediator M in both of 2 different circumstances. The dominant approach to assessing mediation in such a design, proposed by Judd, Kenny, and McClelland (2001), relies on a series of hypothesis tests about components of the mediation model and is not based on an estimate of or formal inference about the indirect effect. In this article we recast Judd et al.'s approach in the path-analytic framework that is now commonly used in between-participant mediation analysis. By so doing, it is apparent how to estimate the indirect effect of a within-participant manipulation on some outcome through a mediator as the product of paths of influence. This path-analytic approach eliminates the need for discrete hypothesis tests about components of the model to support a claim of mediation, as Judd et al.'s method requires, because it relies only on an inference about the product of paths-the indirect effect. We generalize methods of inference for the indirect effect widely used in between-participant designs to this within-participant version of mediation analysis, including bootstrap confidence intervals and Monte Carlo confidence intervals. Using this path-analytic approach, we extend the method to models with multiple mediators operating in parallel and serially and discuss the comparison of indirect effects in these more complex models. We offer macros and code for SPSS, SAS, and Mplus that conduct these analyses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Pervasive sharing of genetic effects in autoimmune disease.

PubMed

Cotsapas, Chris; Voight, Benjamin F; Rossin, Elizabeth; Lage, Kasper; Neale, Benjamin M; Wallace, Chris; Abecasis, Gonçalo R; Barrett, Jeffrey C; Behrens, Timothy; Cho, Judy; De Jager, Philip L; Elder, James T; Graham, Robert R; Gregersen, Peter; Klareskog, Lars; Siminovitch, Katherine A; van Heel, David A; Wijmenga, Cisca; Worthington, Jane; Todd, John A; Hafler, David A; Rich, Stephen S; Daly, Mark J

2011-08-01

Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA) which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44%) immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA)<0.01). We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.

Patients with chronic dizziness following traumatic head injury typically have multiple diagnoses involving combined peripheral and central vestibular dysfunction.

PubMed

Arshad, Q; Roberts, R E; Ahmad, H; Lobo, R; Patel, M; Ham, T; Sharp, D J; Seemungal, B M

2017-04-01

We hypothesised that chronic vestibular symptoms (CVS) of imbalance and dizziness post-traumatic head injury (THI) may relate to: (i) the occurrence of multiple simultaneous vestibular diagnoses including both peripheral and central vestibular dysfunction in individual patients increasing the chance of missed diagnoses and suboptimal treatment; (ii) an impaired response to vestibular rehabilitation since the central mechanisms that mediate rehabilitation related brain plasticity may themselves be disrupted. We report the results of a retrospective analysis of both the comprehensive clinical and vestibular laboratory testing of 20 consecutive THI patients with prominent and persisting vestibular symptoms still present at least 6months post THI. Individual THI patients typically had multiple vestibular diagnoses and unique to this group of vestibular patients, often displayed both peripheral and central vestibular dysfunction. Despite expert neuro-otological management, at two years 20% of patients still had persisting vestibular symptoms. In summary, chronic vestibular dysfunction in THI could relate to: (i) the presence of multiple vestibular diagnoses, increasing the risk of 'missed' vestibular diagnoses leading to persisting symptoms; (ii) the impact of brain trauma which may impair brain plasticity mediated repair mechanisms. Apart from alerting physicians to the potential for multiple vestibular diagnoses in THI, future work to identify the specific deficits in brain function mediating poor recovery from post-THI vestibular dysfunction could provide the rationale for developing new therapy for head injury patients whose vestibular symptoms are resistant to treatment. Copyright © 2017. Published by Elsevier B.V.

The mediating effect of calling on the relationship between medical school students’ academic burnout and empathy

PubMed Central

2017-01-01

Purpose This study is aimed at identifying the relationships between medical school students’ academic burnout, empathy, and calling, and determining whether their calling has a mediating effect on the relationship between academic burnout and empathy. Methods A mixed method study was conducted. One hundred twenty-seven medical students completed a survey. Scales measuring academic burnout, medical students’ empathy, and calling were utilized. For statistical analysis, correlation analysis, descriptive statistics analysis, and hierarchical multiple regression analyses were conducted. For qualitative approach, eight medical students participated in a focus group interview. Results The study found that empathy has a statistically significant, negative correlation with academic burnout, while having a significant, positive correlation with calling. Sense of calling proved to be an effective mediator of the relationship between academic burnout and empathy. Conclusion This result demonstrates that calling is a key variable that mediates the relationship between medical students’ academic burnout and empathy. As such, this study provides baseline data for an education that could improve medical students’ empathy skills. PMID:28870019

Association Between Internalized HIV-Related Stigma and HIV Care Visit Adherence.

PubMed

Rice, Whitney S; Crockett, Kaylee B; Mugavero, Michael J; Raper, James L; Atkins, Ghislaine C; Turan, Bulent

2017-12-15

Internalized HIV-related stigma acts as a barrier to antiretroviral therapy (ART) adherence, but its effects on other HIV care continuum outcomes are unclear. Among 196 HIV clinic patients in Birmingham, AL, we assessed internalized HIV-related stigma and depressive symptom severity using validated multi-item scales and assessed ART adherence using a validated single-item measure. HIV visit adherence (attended out of total scheduled visits) was calculated using data from clinic records. Using covariate-adjusted regression analysis, we investigated the association between internalized stigma and visit adherence. Using path analytic methods with bootstrapping, we tested the mediating role of depressive symptoms in the association between internalized stigma and visit adherence and the mediating role of visit adherence in the association between internalized stigma and ART adherence. Higher internalized stigma was associated with lower visit adherence (B = -0.04, P = 0.04). Black (versus white) race and depressive symptoms were other significant predictors within this model. Mediation analysis yielded no indirect effect through depression in the association between internalized stigma and visit adherence (B = -0.18, SE = 0.11, 95% confidence interval: -0.44 to -0.02) in the whole sample. Supplemental mediated moderation analyses revealed gender-specific effects. Additionally, the effect of internalized stigma on suboptimal ART adherence was mediated by lower visit adherence (B = -0.18, SE = 0.11, 95% confidence interval: -0.44 to -0.02). Results highlight the importance of internalized HIV stigma to multiple and sequential HIV care continuum outcomes. Also, findings suggest multiple intervention targets, including addressing internalized stigma directly, reducing depressive symptoms, and promoting consistent engagement in care.

The moderator-mediator role of social support in early adolescents.

PubMed

Yarcheski, A; Mahon, N E

1999-10-01

The purpose of this study was to examine social support as both a mediator and a moderator of the relationship between perceived stress and symptom patterns in early adolescents. Data were collected from 148 early adolescent boys and girls, ages 12 to 14, who responded to the Perceived Stress Scale, the Personal Resource Questionnaire 85-Part II, and the Symptom Pattern Scale. Using multiple regression analysis procedures specified for the testing of moderation and mediation, results indicated that social support did not play a moderating role in the relationship between perceived stress and symptom patterns, but social support did play a mediating role in this relationship. The findings are interpreted within the two major theoretical orientations that guided the study.

Studies of transformational leadership in the consumer service workgroup: cooperative conflict resolution and the mediating roles of job satisfaction and change commitment.

PubMed

Yang, Yi-Feng

2012-10-01

The present paper evaluates the effect of transformational leadership on job satisfaction and change commitment along with their interconnected effects (mediation) on cooperative conflict resolution (management) in customer service activities in Taiwan. The multi-source samples consist of data from personnel serving at customer centers (workgroups), such as phone service personnel, customer representatives, financial specialists, and front-line salespeople. An empirical study was carried out using a multiple mediation procedure incorporating boot-strapping techniques and PRODCLIN2 with structural equation modeling (SEM) analysis. The results indicate that the main effect of the leadership style on cooperative conflict resolution is mediated by change commitment and job satisfaction.

Estimation of indirect effect when the mediator is a censored variable.

PubMed

Wang, Jian; Shete, Sanjay

2017-01-01

A mediation model explores the direct and indirect effects of an initial variable ( X) on an outcome variable ( Y) by including a mediator ( M). In many realistic scenarios, investigators observe censored data instead of the complete data. Current research in mediation analysis for censored data focuses mainly on censored outcomes, but not censored mediators. In this study, we proposed a strategy based on the accelerated failure time model and a multiple imputation approach. We adapted a measure of the indirect effect for the mediation model with a censored mediator, which can assess the indirect effect at both the group and individual levels. Based on simulation, we established the bias in the estimations of different paths (i.e. the effects of X on M [ a], of M on Y [ b] and of X on Y given mediator M [ c']) and indirect effects when analyzing the data using the existing approaches, including a naïve approach implemented in software such as Mplus, complete-case analysis, and the Tobit mediation model. We conducted simulation studies to investigate the performance of the proposed strategy compared to that of the existing approaches. The proposed strategy accurately estimates the coefficients of different paths, indirect effects and percentages of the total effects mediated. We applied these mediation approaches to the study of SNPs, age at menopause and fasting glucose levels. Our results indicate that there is no indirect effect of association between SNPs and fasting glucose level that is mediated through the age at menopause.

Proteomic analysis of lung tissue by DIGE

USDA-ARS?s Scientific Manuscript database

Lungs perform an essential physiological function, mediated by a complex series of events that involve the coordination of multiple cell types to support not only gaseous exchange, but homeostasis and protection from infection. Guinea pigs are an important animal disease model for a number of infect...

Editorial: Introduction to the Special Section on Causal Inference in Cross Sectional and Longitudinal Mediational Models

PubMed Central

West, Stephen G.

2016-01-01

Psychologists have long had interest in the processes through which antecedent variables produce their effects on the outcomes of ultimate interest (e.g., Wood-worth's Stimulus-Organism-Response model). Models involving such meditational processes have characterized many of the important psychological theories of the 20th century and continue to the present day. However, it was not until Judd and Kenny (1981) and Baron and Kenny (1986) combined ideas from experimental design and structural equation modeling that statistical methods for directly testing such models, now known as mediation analysis, began to be developed. Methodologists have improved these statistical methods, developing new, more efficient estimators for mediated effects. They have also extended mediation analysis to multilevel data structures, models involving multiple mediators, models in which interactions occur, and an array of noncontinuous outcome measures (see MacKinnon, 2008). This work nicely maps on to key questions of applied researchers and has led to an outpouring of research testing meditational models (As of August, 2011, Baron and Kenny's article has had over 24,000 citations according to Google Scholar). PMID:26736046

The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF.

PubMed

Cheng, Ying; Shao, Can; Lathrop, Quinn N

2016-02-01

Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable or multiple variables that may completely or partially mediate the DIF effect. If complete mediation effect is found, the DIF effect is fully accounted for. Through our simulation study, we find that the mediated MIMIC model is very successful in detecting the mediation effect that completely or partially accounts for DIF, while keeping the Type I error rate well controlled for both balanced and unbalanced sample sizes between focal and reference groups. Because it is successful in detecting such mediation effects, the mediated MIMIC model may help explain DIF and give guidance in the revision of a DIF item.

The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

PubMed Central

Cheng, Ying; Shao, Can; Lathrop, Quinn N.

2015-01-01

Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable or multiple variables that may completely or partially mediate the DIF effect. If complete mediation effect is found, the DIF effect is fully accounted for. Through our simulation study, we find that the mediated MIMIC model is very successful in detecting the mediation effect that completely or partially accounts for DIF, while keeping the Type I error rate well controlled for both balanced and unbalanced sample sizes between focal and reference groups. Because it is successful in detecting such mediation effects, the mediated MIMIC model may help explain DIF and give guidance in the revision of a DIF item.

An Index and Test of Linear Moderated Mediation.

PubMed

Hayes, Andrew F

2015-01-01

I describe a test of linear moderated mediation in path analysis based on an interval estimate of the parameter of a function linking the indirect effect to values of a moderator-a parameter that I call the index of moderated mediation. This test can be used for models that integrate moderation and mediation in which the relationship between the indirect effect and the moderator is estimated as linear, including many of the models described by Edwards and Lambert ( 2007 ) and Preacher, Rucker, and Hayes ( 2007 ) as well as extensions of these models to processes involving multiple mediators operating in parallel or in serial. Generalization of the method to latent variable models is straightforward. Three empirical examples describe the computation of the index and the test, and its implementation is illustrated using Mplus and the PROCESS macro for SPSS and SAS.

Causal mediation analysis for longitudinal data with exogenous exposure

PubMed Central

Bind, M.-A. C.; Vanderweele, T. J.; Coull, B. A.; Schwartz, J. D.

2016-01-01

Mediation analysis is a valuable approach to examine pathways in epidemiological research. Prospective cohort studies are often conducted to study biological mechanisms and often collect longitudinal measurements on each participant. Mediation formulae for longitudinal data have been developed. Here, we formalize the natural direct and indirect effects using a causal framework with potential outcomes that allows for an interaction between the exposure and the mediator. To allow different types of longitudinal measures of the mediator and outcome, we assume two generalized mixed-effects models for both the mediator and the outcome. The model for the mediator has subject-specific random intercepts and random exposure slopes for each cluster, and the outcome model has random intercepts and random slopes for the exposure, the mediator, and their interaction. We also expand our approach to settings with multiple mediators and derive the mediated effects, jointly through all mediators. Our method requires the absence of time-varying confounding with respect to the exposure and the mediator. This assumption is achieved in settings with exogenous exposure and mediator, especially when exposure and mediator are not affected by variables measured at earlier time points. We apply the methodology to data from the Normative Aging Study and estimate the direct and indirect effects, via DNA methylation, of air pollution, and temperature on intercellular adhesion molecule 1 (ICAM-1) protein levels. Our results suggest that air pollution and temperature have a direct effect on ICAM-1 protein levels (i.e. not through a change in ICAM-1 DNA methylation) and that temperature has an indirect effect via a change in ICAM-1 DNA methylation. PMID:26272993

Systemically administered gp100 encoding DNA vaccine for melanoma using water-in-oil-in-water multiple emulsion delivery systems.

PubMed

Kalariya, Mayurkumar; Amiji, Mansoor M

2013-09-10

The purpose of this study was to develop a water-in-oil-in-water (W/O/W) multiple emulsions-based vaccine delivery system for plasmid DNA encoding the gp100 peptide antigen for melanoma immunotherapy. The gp100 encoding plasmid DNA was encapsulated in the inner-most aqueous phase of squalane oil containing W/O/W multiple emulsions using a two-step emulsification method. In vitro transfection ability of the encapsulated plasmid DNA was investigated in murine dendritic cells by transgene expression analysis using fluorescence microscopy and ELISA methods. Prophylactic immunization using the W/O/W multiple emulsions encapsulated the gp100 encoding plasmid DNA vaccine significantly reduced tumor volume in C57BL/6 mice during subsequent B16-F10 tumor challenge. In addition, serum Th1 cytokine levels and immuno-histochemistry of excised tumor tissues indicated activation of cytotoxic T-lymphocytes mediated anti-tumor immunity causing tumor growth suppression. The W/O/W multiple emulsions-based vaccine delivery system efficiently delivers the gp100 plasmid DNA to induce cell-mediated anti-tumor immunity. Copyright © 2013 Elsevier B.V. All rights reserved.

Understanding how pain education causes changes in pain and disability: protocol for a causal mediation analysis of the PREVENT trial.

PubMed

Lee, Hopin; Moseley, G Lorimer; Hübscher, Markus; Kamper, Steven J; Traeger, Adrian C; Skinner, Ian W; McAuley, James H

2015-07-01

Pain education is a complex intervention developed to help clinicians manage low back pain. Although complex interventions are usually evaluated by their effects on outcomes, such as pain or disability, most do not directly target these outcomes; instead, they target intermediate factors that are presumed to be associated with the outcomes. The mechanisms underlying treatment effects, or the effect of an intervention on an intermediate factor and its subsequent effect on outcome, are rarely investigated in clinical trials. This leaves a gap in the evidence for understanding how treatments exert their effects on outcomes. Mediation analysis provides a method for identifying and quantifying the mechanisms that underlie interventions. To determine whether the effect of pain education on pain and disability is mediated by changes in self-efficacy, catastrophisation and back pain beliefs. Causal mediation analysis of the PREVENT randomised controlled trial. Two hundred and two participants with acute low back pain from primary care clinics in the Sydney metropolitan area. Participants will be randomised to receive either 'pain education' (intervention group) or 'sham education' (control group). All outcome measures (including patient characteristics), primary outcome measures (pain and disability), and putative mediating variables (self-efficacy, catastrophisation and back pain beliefs) will be measured prior to randomisation. Putative mediators and primary outcome measures will be measured 1 week after the intervention, and primary outcome measures will be measured 3 months after the onset of low back pain. Causal mediation analysis under the potential outcomes framework will be used to test single and multiple mediator models. A sensitivity analysis will be conducted to evaluate the robustness of the estimated mediation effects on the influence of violating sequential ignorability--a critical assumption for causal inference. Mediation analysis of clinical trials can estimate how much the total effect of the treatment on the outcome is carried through an indirect path. Using mediation analysis to understand these mechanisms can generate evidence that can be used to tailor treatments and optimise treatment effects. In this study, the causal mediation effects of a pain education intervention for acute non-specific low back pain will be estimated. This knowledge is critical for further development and refinement of interventions for conditions such as low back pain. Copyright © 2015 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

The mechanisms mediating the effects of poverty on children's intellectual development.

PubMed

Guo, G; Harris, K M

2000-11-01

Although adverse consequences of poverty for children are documented widely, little is understood about the mechanisms through which the effects of poverty disadvantage young children. In this analysis we investigate multiple mechanisms through which poverty affects a child's intellectual development. Using data from the NLSY and structural equation models, we have constructed five latent factors (cognitive stimulation, parenting style, physical environment, child's ill health at birth, and ill health in childhood) and have allowed these factors, along with child care, to mediate the effects of poverty and other exogenous variables. We produce two main findings. First, the influence of family poverty on children's intellectual development is mediated completely by the intervening mechanisms measured by our latent factors. Second, our analysis points to cognitive stimulation in the home, and (to a lesser extent) to parenting style, physical environment of the home, and poor child health at birth, as mediating factors that are affected by lack of income and that influence children's intellectual development.

Influence of dorsolateral prefrontal cortex and ventral striatum on risk avoidance in addiction: a mediation analysis.

PubMed

Yamamoto, Dorothy J; Woo, Choong-Wan; Wager, Tor D; Regner, Michael F; Tanabe, Jody

2015-04-01

Alterations in frontal and striatal function are hypothesized to underlie risky decision making in drug users, but how these regions interact to affect behavior is incompletely understood. We used mediation analysis to investigate how prefrontal cortex and ventral striatum together influence risk avoidance in abstinent drug users. Thirty-seven abstinent substance-dependent individuals (SDI) and 43 controls underwent fMRI while performing a decision-making task involving risk and reward. Analyses of a priori regions-of-interest tested whether activity in dorsolateral prefrontal cortex (DLPFC) and ventral striatum (VST) explained group differences in risk avoidance. Whole-brain analysis was conducted to identify brain regions influencing the negative VST-risk avoidance relationship. Right DLPFC (RDLPFC) positively mediated the group-risk avoidance relationship (p < 0.05); RDLPFC activity was higher in SDI and predicted higher risk avoidance across groups, controlling for SDI vs. Conversely, VST activity negatively influenced risk avoidance (p < 0.05); it was higher in SDI, and predicted lower risk avoidance. Whole-brain analysis revealed that, across group, RDLPFC and left temporal-parietal junction positively (p ≤ 0.001) while right thalamus and left middle frontal gyrus negatively (p < 0.005) mediated the VST activity-risk avoidance relationship. RDLPFC activity mediated less risky decision making while VST mediated more risky decision making across drug users and controls. These results suggest a dual pathway underlying decision making, which, if imbalanced, may adversely influence choices involving risk. Modeling contributions of multiple brain systems to behavior through mediation analysis could lead to a better understanding of mechanisms of behavior and suggest neuromodulatory treatments for addiction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Influence of dorsolateral prefrontal cortex and ventral striatum on risk avoidance in addiction: a mediation analysis*

PubMed Central

Yamamoto, Dorothy J.; Woo, Choong-Wan; Wager, Tor D.; Regner, Michael F.; Tanabe, Jody

2015-01-01

Background Alterations in frontal and striatal function are hypothesized to underlie risky decision-making in drug users, but how these regions interact to affect behavior is incompletely understood. We used mediation analysis to investigate how prefrontal cortex and ventral striatum together influence risk avoidance in abstinent drug users. Method Thirty-seven abstinent substance-dependent individuals (SDI) and 43 controls underwent fMRI while performing a decision-making task involving risk and reward. Analyses of a priori regions-of-interest tested whether activity in dorsolateral prefrontal cortex (DLPFC) and ventral striatum (VST) explained group differences in risk avoidance. Whole-brain analysis was conducted to identify brain regions influencing the negative VST-risk avoidance relationship. Results Right DLPFC (RDLPFC) positively mediated the group-risk avoidance relationship (p < 0.05); RDLPFC activity was higher in SDI and predicted higher risk avoidance across groups, controlling for SDI vs. controls. Conversely, VST activity negatively influenced risk avoidance (p < 0.05); it was higher in SDI, and predicted lower risk avoidance. Whole-brain analysis revealed that, across group, RDLPFC and left temporal-parietal junction positively (p ≤ 0.001) while right thalamus and left middle frontal gyrus negatively (p < 0.005) mediated the VST activity-risk avoidance relationship. Conclusion RDLPFC activity mediated less risky decision-making while VST mediated more risky decision-making across drug users and controls. These results suggest a dual pathway underlying decision-making, which, if imbalanced, may adversely influence choices involving risk. Modeling contributions of multiple brain systems to behavior through mediation analysis could lead to a better understanding of mechanisms of behavior and suggest neuromodulatory treatments for addiction. PMID:25736619

Extracellular vesicle communication pathways as regulatory targets of oncogenic transformation.

PubMed

Choi, Dongsic; Lee, Tae Hoon; Spinelli, Cristiana; Chennakrishnaiah, Shilpa; D'Asti, Esterina; Rak, Janusz

2017-07-01

Pathogenesis of human cancers bridges intracellular oncogenic driver events and their impact on intercellular communication. Among multiple mediators of this 'pathological connectivity' the role of extracellular vesicles (EVs) and their subsets (exosomes, ectosomes, oncosomes) is of particular interest for several reasons. The release of EVs from cancer cells represents a unique mechanism of regulated expulsion of bioactive molecules, a process that also mediates cell-to-cell transfer of lipids, proteins, and nucleic acids. Biological effects of these processes have been implicated in several aspects of cancer-related pathology, including tumour growth, invasion, angiogenesis, metastasis, immunity and thrombosis. Notably, the emerging evidence suggests that oncogenic mutations may impact several aspects of EV-mediated cell-cell communication including: (i) EV release rate and protein content; (ii) molecular composition of cancer EVs; (iii) the inclusion of oncogenic and mutant macromolecules in the EV cargo; (iv) EV-mediated release of genomic DNA; (v) deregulation of mechanisms responsible for EV biogenesis (vesiculome) and (vi) mechanisms of EV uptake by cancer cells. Intriguingly, EV-mediated intercellular transfer of mutant and oncogenic molecules between subpopulations of cancer cells, their indolent counterparts and stroma may exert profound biological effects that often resemble (but are not tantamount to) oncogenic transformation, including changes in cell growth, clonogenicity and angiogenic phenotype, or cause cell stress and death. However, several biological barriers likely curtail a permanent horizontal transformation of normal cells through EV-mediated mechanisms. The ongoing analysis and targeting of EV-mediated intercellular communication pathways can be viewed as a new therapeutic paradigm in cancer, while the analysis of oncogenic cargo contained in EVs released from cancer cells into biofluids is being developed for clinical use as a biomarker and companion diagnostics. Indeed, studies are underway to further explore the multiple links between molecular causality in cancer and various aspects of cellular vesiculation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease

PubMed Central

Peters, James E.; Lyons, Paul A.; Lee, James C.; Richard, Arianne C.; Fortune, Mary D.; Newcombe, Paul J.; Richardson, Sylvia; Smith, Kenneth G. C.

2016-01-01

Genome-wide association studies (GWAS) have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs) is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91), anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46) and healthy controls (n = 43), revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases. PMID:27015630

Emerging functions of multi-protein complex Mediator with special emphasis on plants.

PubMed

Malik, Naveen; Agarwal, Pinky; Tyagi, Akhilesh

2017-10-01

Mediator is a multi-subunit protein complex which is involved in transcriptional regulation in yeast and other eukaryotes. As a co-activator, it connects information from transcriptional activators/repressors to transcriptional machinery including RNA polymerase II and general transcription factors. It is not only involved in transcription initiation but also has important roles to play in transcription elongation and termination. Functional attributes of different Mediator subunits have been largely defined in yeast and mammalian systems earlier, while such studies in plants have gained momentum recently. Mediator regulates various processes related to plant development and is also involved in biotic and abiotic stress response. Thus, plant Mediator, like yeast and mammalian Mediator complex, is indispensable for plant growth and survival. Interaction of its multiple subunits with other regulatory proteins and their ectopic expression or knockdown in model plant like Arabidopsis and certain crop plants are paving the way to biochemical analysis and unravel molecular mechanisms of action of Mediator in plants.

Moderators of the mediated effect of intentions, planning, and saturated-fat intake in obese individuals.

PubMed

Soureti, Anastasia; Hurling, Robert; van Mechelen, Willem; Cobain, Mark; ChinAPaw, Mai

2012-05-01

The present study aimed to advance our understanding of health-related theory, that is, the alleged intention-behavior gap in an obese population. It examined the mediating effects of planning on the intention-behavior relationship and the moderated mediation effects of age, self-efficacy and intentions within this relationship. The study was conducted over a five-week period. Complete data from 571 obese participants were analyzed. The moderated mediation hypothesis was conducted using multiple-regression analysis. To test our theoretical model, intentions (Week 2), action self-efficacy (Week 2), maintenance self-efficacy (Week 5), planning (Week 5), and saturated-fat intake (Weeks 1 and 5) were measured by self-report. As hypothesized, planning mediated the intention-behavior relationship for perceived (two-item scale) and percentage-saturated-fat intake (measured by a food frequency questionnaire). Age, self-efficacy, and intention acted as moderators in the above mediation analysis. In specific, younger individuals, those with stronger intention, and people with higher levels of maintenance self-efficacy at higher levels of planning showed greater reductions in their perceived saturated-fat intake. For successful behavior change, knowledge of its mediators and moderators is needed. Future interventions targeting planning to change saturated-fat intake should be guided by people's intentions, age, and self-efficacy levels.

Testing a multiple mediation model of Asian American college students' willingness to see a counselor.

PubMed

Kim, Paul Youngbin; Park, Irene J K

2009-07-01

Adapting the theory of reasoned action, the present study examined help-seeking beliefs, attitudes, and intent among Asian American college students (N = 110). A multiple mediation model was tested to see if the relation between Asian values and willingness to see a counselor was mediated by attitudes toward seeking professional psychological help and subjective norm. A bootstrapping procedure was used to test the multiple mediation model. Results indicated that subjective norm was the sole significant mediator of the effect of Asian values on willingness to see a counselor. The findings highlight the importance of social influences on help-seeking intent among Asian American college students.

[The mediating role of anger in the relationship between automatic thoughts and physical aggression in adolescents].

PubMed

Yavuzer, Yasemin; Karataş, Zeynep

2013-01-01

This study aimed to examine the mediating role of anger in the relationship between automatic thoughts and physical aggression in adolescents. The study included 224 adolescents in the 9th grade of 3 different high schools in central Burdur during the 2011-2012 academic year. Participants completed the Aggression Questionnaire and Automatic Thoughts Scale in their classrooms during counseling sessions. Data were analyzed using simple and multiple linear regression analysis. There were positive correlations between the adolescents' automatic thoughts, and physical aggression, and anger. According to regression analysis, automatic thoughts effectively predicted the level of physical aggression (b= 0.233, P < 0.001)) and anger (b= 0.325, P < 0.001). Analysis of the mediating role of anger showed that anger fully mediated the relationship between automatic thoughts and physical aggression (Sobel z = 5.646, P < 0.001). Anger fully mediated the relationship between automatic thoughts and physical aggression. Providing adolescents with anger management skills training is very important for the prevention of physical aggression. Such training programs should include components related to the development of an awareness of dysfunctional and anger-triggering automatic thoughts, and how to change them. As the study group included adolescents from Burdur, the findings can only be generalized to groups with similar characteristics.

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2011-01-01

The purpose of this paper is to clarify the assumptions that must be met if this--multiple site, multiple mediator--strategy, hereafter referred to as "MSMM," is to identify the average causal effects (ATE) in the populations of interest. The authors' investigation of the assumptions of the multiple-mediator, multiple-site IV model demonstrates…

Learner Analysis Framework for Globalized E-Learning: A Case Study

ERIC Educational Resources Information Center

Saxena, Mamta

2011-01-01

The shift to technology-mediated modes of instructional delivery and increased global connectivity has led to the rise in globalized e-learning programs. Educational institutions face multiple challenges as they seek to design effective, engaging, and culturally competent instruction for an increasingly diverse learner population. The purpose of…

Latino Adolescents' Academic Success: The Role of Discrimination, Academic Motivation, and Gender

ERIC Educational Resources Information Center

Alfaro, Edna C.; Umana-Taylor, Adriana J.; Gonzales-Backen, Melinda A.; Bamaca, Mayra Y.; Zeiders, Katharine H.

2009-01-01

Guided by the academic resilience perspective, the current longitudinal study examined whether academic motivation mediated the relation between Latino adolescents' (N = 221) experiences with discrimination and their academic success. The potential moderating role of gender was also examined. Using multiple group analysis in structural equation…

Indirect effects of exercise on emotional eating through psychological predictors of weight loss in women.

PubMed

Annesi, James J; Mareno, Nicole

2015-12-01

An improved understanding of how weight-loss interventions might be tailored to improve emotional eating is required. This study aimed to assess mediation of the relationship between increased exercise and decreased emotional eating so that behavioral treatments might be optimized. After randomization, women with obesity (N = 108; mean age = 48 years) were assigned to either a previously tested treatment of manual-based self-help for nutrition and exercise plus brief phone follow-ups, or a new protocol of cognitive-behavioral methods of exercise support intended to carry-over psychological improvements to better controlled eating and weight loss. A community-based field setting was incorporated. Validated self-report measures were administered over 6 months. Significant overall improvements in exercise outputs, emotional eating, mood, and self-regulation and self-efficacy for controlled eating were found. The newly developed treatment protocol demonstrated significantly greater improvements in exercise outputs and self-regulation. In a multiple mediation analysis, changes in self-regulation, self-efficacy, and mood significantly mediated the relationship between changes in exercise and emotional eating. Changes in self-efficacy and mood were significant independent mediators. Within follow-up analyses, the substitution of emotional eating subscales that addressed specific moods, and a subscale of self-efficacy for controlled eating that addressed that factor specifically in the presence of negative emotions, yielded results generally consistent with those of the multiple mediation analysis. Results suggested a psychological pathway of exercise's association with emotional eating changes in women with obesity. Guided by the present findings, tailoring exercise support and leveraging it to induce specific psychological improvements might reduce emotional eating and improve weight-management outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

ERIC Educational Resources Information Center

Yang, Hongfei; Li, Juan

2016-01-01

The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

Causal mediation analysis for longitudinal data with exogenous exposure.

PubMed

Bind, M-A C; Vanderweele, T J; Coull, B A; Schwartz, J D

2016-01-01

Mediation analysis is a valuable approach to examine pathways in epidemiological research. Prospective cohort studies are often conducted to study biological mechanisms and often collect longitudinal measurements on each participant. Mediation formulae for longitudinal data have been developed. Here, we formalize the natural direct and indirect effects using a causal framework with potential outcomes that allows for an interaction between the exposure and the mediator. To allow different types of longitudinal measures of the mediator and outcome, we assume two generalized mixed-effects models for both the mediator and the outcome. The model for the mediator has subject-specific random intercepts and random exposure slopes for each cluster, and the outcome model has random intercepts and random slopes for the exposure, the mediator, and their interaction. We also expand our approach to settings with multiple mediators and derive the mediated effects, jointly through all mediators. Our method requires the absence of time-varying confounding with respect to the exposure and the mediator. This assumption is achieved in settings with exogenous exposure and mediator, especially when exposure and mediator are not affected by variables measured at earlier time points. We apply the methodology to data from the Normative Aging Study and estimate the direct and indirect effects, via DNA methylation, of air pollution, and temperature on intercellular adhesion molecule 1 (ICAM-1) protein levels. Our results suggest that air pollution and temperature have a direct effect on ICAM-1 protein levels (i.e. not through a change in ICAM-1 DNA methylation) and that temperature has an indirect effect via a change in ICAM-1 DNA methylation. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The relationship among self-efficacy, perfectionism and academic burnout in medical school students.

PubMed

Yu, Ji Hye; Chae, Su Jin; Chang, Ki Hong

2016-03-01

The purpose of this study was to examine the relationship among academic self-efficacy, socially-prescribed perfectionism, and academic burnout in medical school students and to determine whether academic self-efficacy had a mediating role in the relationship between perfectionism and academic burnout. A total of 244 first-year and second-year premed medical students and first- to fourth-year medical students were enrolled in this study. As study tools, socially-prescribed perfectionism, academic self-efficacy, and academic burnout scales were utilized. For data analysis, correlation analysis, multiple regression analysis, and hierarchical multiple regression analyses were conducted. Academic burnout had correlation with socially-prescribed perfectionism. It had negative correlation with academic self-efficacy. Socially-prescribed perfectionism and academic self-efficacy had 54% explanatory power for academic burnout. When socially-prescribed perfectionism and academic self-efficacy were simultaneously used as input, academic self-efficacy partially mediated the relationship between socially-prescribed perfectionism and academic burnout. Socially-prescribed perfectionism had a negative effect on academic self-efficacy, ultimately triggering academic burnout. This suggests that it is important to have educational and counseling interventions to improve academic self-efficacy by relieving academic burnout of medical school students.

The relationship among self-efficacy, perfectionism and academic burnout in medical school students

PubMed Central

Yu, Ji Hye; Chae, Su Jin; Chang, Ki Hong

2016-01-01

Purpose: The purpose of this study was to examine the relationship among academic self-efficacy, socially-prescribed perfectionism, and academic burnout in medical school students and to determine whether academic self-efficacy had a mediating role in the relationship between perfectionism and academic burnout. Methods: A total of 244 first-year and second-year premed medical students and first- to fourth-year medical students were enrolled in this study. As study tools, socially-prescribed perfectionism, academic self-efficacy, and academic burnout scales were utilized. For data analysis, correlation analysis, multiple regression analysis, and hierarchical multiple regression analyses were conducted. Results: Academic burnout had correlation with socially-prescribed perfectionism. It had negative correlation with academic self-efficacy. Socially-prescribed perfectionism and academic self-efficacy had 54% explanatory power for academic burnout. When socially-prescribed perfectionism and academic self-efficacy were simultaneously used as input, academic self-efficacy partially mediated the relationship between socially-prescribed perfectionism and academic burnout. Conclusion: Socially-prescribed perfectionism had a negative effect on academic self-efficacy, ultimately triggering academic burnout. This suggests that it is important to have educational and counseling interventions to improve academic self-efficacy by relieving academic burnout of medical school students. PMID:26838568

Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis.

PubMed

Jurynczyk, Maciej; Geraldes, Ruth; Probert, Fay; Woodhall, Mark R; Waters, Patrick; Tackley, George; DeLuca, Gabriele; Chandratre, Saleel; Leite, Maria I; Vincent, Angela; Palace, Jacqueline

2017-03-01

Brain imaging characteristics of MOG antibody disease are largely unknown and it is unclear whether they differ from those of multiple sclerosis and AQP4 antibody disease. The aim of this study was to identify brain imaging discriminators between those three inflammatory central nervous system diseases in adults and children to support diagnostic decisions, drive antibody testing and generate disease mechanism hypotheses. Clinical brain scans of 83 patients with brain lesions (67 in the training and 16 in the validation cohort, 65 adults and 18 children) with MOG antibody (n = 26), AQP4 antibody disease (n = 26) and multiple sclerosis (n = 31) recruited from Oxford neuromyelitis optica and multiple sclerosis clinical services were retrospectively and anonymously scored on a set of 29 predefined magnetic resonance imaging features by two independent raters. Principal component analysis was used to perform an overview of patients without a priori knowledge of the diagnosis. Orthogonal partial least squares discriminant analysis was used to build models separating diagnostic groups and identify best classifiers, which were then tested on an independent cohort set. Adults and children with MOG antibody disease frequently had fluffy brainstem lesions, often located in pons and/or adjacent to fourth ventricle. Children across all conditions showed more frequent bilateral, large, brainstem and deep grey matter lesions. MOG antibody disease spontaneously separated from multiple sclerosis but overlapped with AQP4 antibody disease. Multiple sclerosis was discriminated from MOG antibody disease and from AQP4 antibody disease with high predictive values, while MOG antibody disease could not be accurately discriminated from AQP4 antibody disease. Best classifiers between MOG antibody disease and multiple sclerosis were similar in adults and children, and included ovoid lesions adjacent to the body of lateral ventricles, Dawson's fingers, T1 hypointense lesions (multiple sclerosis), fluffy lesions and three lesions or less (MOG antibody). In the validation cohort patients with antibody-mediated conditions were differentiated from multiple sclerosis with high accuracy. Both antibody-mediated conditions can be clearly separated from multiple sclerosis on conventional brain imaging, both in adults and children. The overlap between MOG antibody oligodendrocytopathy and AQP4 antibody astrocytopathy suggests that the primary immune target is not the main substrate for brain lesion characteristics. This is also supported by the clear distinction between multiple sclerosis and MOG antibody disease both considered primary demyelinating conditions. We identify discriminatory features, which may be useful in classifying atypical multiple sclerosis, seronegative neuromyelitis optica spectrum disorders and relapsing acute disseminated encephalomyelitis, and characterizing cohorts for antibody discovery. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Determining the relative importance of the mechanisms of behavior change within Alcoholics Anonymous: a multiple mediator analysis.

PubMed

Kelly, John F; Hoeppner, Bettina; Stout, Robert L; Pagano, Maria

2012-02-01

Evidence indicates that Alcoholics Anonymous (AA) participation reduces relapse risk but less is known about the mechanisms through which AA confers this benefit. Initial studies indicate self-efficacy, negative affect, adaptive social networks and spiritual practices are mediators of this effect, but because these have been tested in isolation, their relative importance remains elusive. This study tested multiple mediators simultaneously to help determine the most influential pathways. Prospective, statistically controlled, naturalistic investigation examined the extent to which these previously identified mechanisms mediated AA attendance effects on alcohol outcomes controlling for baseline outcome values, mediators, treatment, and other confounders. Nine clinical sites within the United States. Adults (n = 1726) suffering from alcohol use disorder (AUD) initially enrolled in a randomized study with two arms: aftercare (n = 774); and out-patient (n = 952) comparing three out-patient treatments (Project MATCH). AA attendance during treatment; mediators at 9 months; and outcomes [percentage of days abstinent (PDA) and drinks per drinking day (DDD)] at 15 months. Among out-patients the effect of AA attendance on alcohol outcomes was explained primarily by adaptive social network changes and increases in social abstinence self-efficacy. Among more impaired aftercare patients, in addition to mediation through adaptive network changes and increases in social self-efficacy, AA lead to better outcomes through increasing spirituality/religiosity and by reducing negative affect. The degree to which mediators explained the relationship between AA and outcomes ranged from 43% to 67%. While Alcoholics Anonymous facilitates recovery by mobilizing several processes simultaneously, it is changes in social factors which appear to be of primary importance. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

The insulin effect on cerebrocortical theta activity is associated with serum concentrations of saturated nonesterified Fatty acids.

PubMed

Tschritter, Otto; Preissl, Hubert; Hennige, Anita M; Sartorius, Tina; Grichisch, Yuko; Stefan, Norbert; Guthoff, Martina; Düsing, Stephan; Machann, Jürgen; Schleicher, Erwin; Cegan, Alexander; Birbaumer, Niels; Fritsche, Andreas; Häring, Hans-Ulrich

2009-11-01

Insulin action in the brain contributes to adequate regulation of body weight, neuronal survival, and suppression of endogenous glucose production. We previously demonstrated by magnetoencephalography in lean humans that insulin stimulates activity in beta and theta frequency bands, whereas this effect was abolished in obese individuals. The present study aims to define metabolic signals associated with the suppression of the cerebrocortical response in obese humans. We determined insulin-mediated modulation of spontaneous cerebrocortical activity by magnetoencephalography during a hyperinsulinemic euglycemic clamp and related it to measures of ectopic fat deposition and mediators of peripheral insulin resistance. Visceral fat mass and intrahepatic lipid content were quantified by magnetic resonance imaging and spectroscopy. Multiple regression analysis was used to analyze associations of cerebrocortical insulin sensitivity and metabolic markers related to obesity. Forty-nine healthy, nondiabetic humans participated in the study. In a multiple regression, insulin-mediated stimulation of theta activity was negatively correlated to body mass index, visceral fat mass, and intrahepatic lipid content. Although fasting saturated nonesterified fatty acids mediated the correlations of theta activity with abdominal and intrahepatic lipid stores, adipocytokines displayed no independent correlation with insulin-mediated cortical activity in the theta frequency band. Thus, insulin action at the level of cerebrocortical activity in the brain is diminished in the presence of elevated levels of saturated nonesterified fatty acids.

Multiple functions of the S-phase checkpoint mediator.

PubMed

Tanaka, Katsunori

2010-01-01

There is mounting evidence that replication defects are the major source of spontaneous genomic instability in cells, and that S-phase checkpoints are the principal defense against such instability. The S-phase checkpoint mediator protein Mrc1/Claspin mediates the checkpoint response to replication stress by facilitating phosphorylation of effector kinase by a sensor kinase. In this review, the multiple functions and the regulation of the S-phase checkpoint mediator are discussed.

A longitudinal analysis of cognitive dysfunction, coping, and depression in multiple sclerosis.

PubMed

Rabinowitz, Amanda R; Arnett, Peter A

2009-09-01

Using a longitudinal design, the authors examined coping and cognitive functioning in the development of depression in individuals with multiple sclerosis (MS). Coping style was evaluated in 2 conceptually distinct roles: as moderator and mediator of the impact of cognitive dysfunction on depression. Using indices derived from the COPE (C. S. Carver, M. F. Scheier, & J. K. Weintraub, 1989), the authors operationalized coping in 3 ways-as active, avoidant, and an index accounting for relative levels of both. Coping both moderated and partially mediated the relationship between cognitive dysfunction and depression. Moderation results suggest that the relationship between cognitive dysfunction and depression is dependent on coping style-adaptive coping protects individuals from experiencing depression related to their cognitive deficits; however, when individuals use maladaptive coping, cognitive dysfunction puts them at risk for depression. Mediational results suggest that cognitive dysfunction leads to depression partially due to cognitive dysfunction's effects on coping. That is, cognitive deficits may impair individuals' ability to use adaptive coping strategies, leaving them more likely to use maladaptive strategies. Clinical and theoretical implications of these findings are discussed.

Individual and family factors associated with self-esteem in young people with epilepsy: A multiple mediation analysis.

PubMed

Chew, Judith; Haase, Anne M; Carpenter, John

2017-01-01

As young people experience added demands from living with epilepsy, which may lead to poor psychosocial adjustment, it is essential to examine mechanisms of change to provide practitioners with knowledge to develop effective interventions. The aim of this study was to examine individual and family-level factors - stress and illness perceptions, coping behaviors and family resilience - that promote or maintain young people's self-esteem. From November 2013 to August 2014, young people attending a neurology clinic in KK Women's and Children's Hospital, Singapore, participated in a cross-sectional survey (n=152; 13-16years old). Multiple mediation analyses were conducted to evaluate whether these variables mediated the relationship between illness severity (i.e., low, moderate, high) and self-esteem. Multiple mediation analyses demonstrated that illness severity had a direct effect on young people's self-esteem. Compared to those with moderate illness severity (reference group), young people with low severity had significantly higher self-esteem (c=3.42, p<0.05); while those with high severity had a more negative view of themselves (c=-3.93, p<0.001). Illness severity also had an indirect influence on self-esteem through its effects on mediators, such as perceived stress, illness perceptions and family resilience (D 1 : Total ab=3.46, 95% CI 1.13, 5.71; D 2 : Total ab=-2.80, 95% CI -4.35, -1.30). However, young people's coping levels did not predict their self-esteem, when accounting for the effects of other variables. The continued presence of seizure occurrences is likely to place greater demands on young people and their families: in turn, increased stress and negative illness perceptions negatively affected family processes that promote resilience. As the mediating effect of these modifiable factors were above and beyond the contributions of illness characteristics and young people's levels of coping, this has implications for developing individual and family interventions aimed to support young people living with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with Real-Time Simultaneous Detection of Multiple DNA Targets.

PubMed

Seok, Youngung; Joung, Hyou-Arm; Byun, Ju-Young; Jeon, Hyo-Sung; Shin, Su Jeong; Kim, Sanghyo; Shin, Young-Beom; Han, Hyung Soo; Kim, Min-Gon

2017-01-01

Paper-based diagnostic devices have many advantages as a one of the multiple diagnostic test platforms for point-of-care (POC) testing because they have simplicity, portability, and cost-effectiveness. However, despite high sensitivity and specificity of nucleic acid testing (NAT), the development of NAT based on a paper platform has not progressed as much as the others because various specific conditions for nucleic acid amplification reactions such as pH, buffer components, and temperature, inhibitions from technical differences of paper-based device. Here, we propose a paper-based device for performing loop-mediated isothermal amplification (LAMP) with real-time simultaneous detection of multiple DNA targets. We determined the optimal chemical components to enable dry conditions for the LAMP reaction without lyophilization or other techniques. We also devised the simple paper device structure by sequentially stacking functional layers, and employed a newly discovered property of hydroxynaphthol blue fluorescence to analyze real-time LAMP signals in the paper device. This proposed platform allowed analysis of three different meningitis DNA samples in a single device with single-step operation. This LAMP-based multiple diagnostic device has potential for real-time analysis with quantitative detection of 10 2 -10 5 copies of genomic DNA. Furthermore, we propose the transformation of DNA amplification devices to a simple and affordable paper system approach with great potential for realizing a paper-based NAT system for POC testing.

A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with Real-Time Simultaneous Detection of Multiple DNA Targets

PubMed Central

Seok, Youngung; Joung, Hyou-Arm; Byun, Ju-Young; Jeon, Hyo-Sung; Shin, Su Jeong; Kim, Sanghyo; Shin, Young-Beom; Han, Hyung Soo; Kim, Min-Gon

2017-01-01

Paper-based diagnostic devices have many advantages as a one of the multiple diagnostic test platforms for point-of-care (POC) testing because they have simplicity, portability, and cost-effectiveness. However, despite high sensitivity and specificity of nucleic acid testing (NAT), the development of NAT based on a paper platform has not progressed as much as the others because various specific conditions for nucleic acid amplification reactions such as pH, buffer components, and temperature, inhibitions from technical differences of paper-based device. Here, we propose a paper-based device for performing loop-mediated isothermal amplification (LAMP) with real-time simultaneous detection of multiple DNA targets. We determined the optimal chemical components to enable dry conditions for the LAMP reaction without lyophilization or other techniques. We also devised the simple paper device structure by sequentially stacking functional layers, and employed a newly discovered property of hydroxynaphthol blue fluorescence to analyze real-time LAMP signals in the paper device. This proposed platform allowed analysis of three different meningitis DNA samples in a single device with single-step operation. This LAMP-based multiple diagnostic device has potential for real-time analysis with quantitative detection of 102-105 copies of genomic DNA. Furthermore, we propose the transformation of DNA amplification devices to a simple and affordable paper system approach with great potential for realizing a paper-based NAT system for POC testing. PMID:28740546

Mediatizing Higher Education Policies: Discourses about Quality Education in the Media

ERIC Educational Resources Information Center

Cabalin, Cristian

2015-01-01

This article presents a critical-political discourse analysis of the media debate over quality assurance in higher education, which occurred in Chile after the 2011 student movement. Students criticized the privatization of higher education and the multiple flaws of this sector, which included corruption scandals during the process of quality…

Parenting behavior and the Interpersonal-Psychological Theory of Suicide: a mediated moderation analysis with adolescents.

PubMed

Cero, Ian; Sifers, Sarah K

2013-09-25

Multiple features of parenting have been associated with development of suicide-related behaviors in adolescents. However, findings are inconsistent on which aspects of parenting are protective or harmful and why. This investigation sought to reconcile these discrepancies through the Interpersonal-Psychological Theory of Suicide (IPTS), which argues that suicide ideation and the capability to attempt suicide are etiologically distinct. Responses of 200 Midwestern public school students to the Profiles of Student Life: Attitudes and Behavior survey were analyzed using mediated moderation analysis. Participant sex significantly moderated the relationships between parenting variables and suicide attempts and these relationships were accounted for by IPTS variables. Specifically, the effect of parental support on suicide attempts was twice as strong for girls. Self-esteem mediated this interaction (b=-.011, SE(boot)=.008, p<.05, κ(2)=.07). Conversely, the effect of parental boundaries on suicide attempts was significant for boys, but not for girls, and was mediated by exposure to violence (b=.029, SE(boot)=.021, p<.05, κ(2)=.07). This study involved retrospective report with proxy-measures of IPTS constructs. Future research should consider multiple informants and additional measures. Findings highlight potential mechanisms by which parenting behaviors could influence sex differences in adolescent suicide-relate behaviors, and that some parenting behavior is associated with reduced adolescent suicide attempts. Findings also suggest the IPTS is able to account for previously identified inconsistencies in the effects of parenting behaviors on adolescent suicide-related behaviors. Implications for theory and intervention are discussed. © 2013 Elsevier B.V. All rights reserved.

ADHD and risky sexual behavior in adolescents: Conduct problems and substance use as mediators of risk

PubMed Central

Sarver, Dustin E.; McCart, Michael R.; Sheidow, Ashli J.; Letourneau, Elizabeth J.

2015-01-01

Background Recent studies have linked attention-deficit/hyperactivity disorder (ADHD) to elevated rates of risky sexual behavior (RSB) in adult samples. The current study tested whether ADHD symptoms were associated with RSB among adolescents, and examined comorbid conduct problems and problematic substance use as joint mediators of this association. Methods ADHD symptoms, conduct problems (oppositional defiant disorder/conduct disorder symptoms), problematic alcohol use (alcohol use disorder symptoms, alcohol use frequency), problematic marijuana use (marijuana use disorder symptoms, marijuana use frequency), and RSB were assessed among an ethnically diverse cross-sectional sample of adolescents (N=115; mean age=14.9 years) involved in the juvenile justice system. Results Bootstrapped mediation models revealed an initial association between ADHD symptoms and RSB that was accounted for fully by the influence of problematic alcohol and marijuana use, but not conduct problems. A follow-up multiple groups mediation analysis demonstrated that the relationship between ADHD symptoms and RSB emerged only among youth with clinically elevated conduct problems, and that problematic marijuana use fully accounted for this relationship. Hyperactive/impulsive but not inattentive symptoms were related to RSB, although the pattern of indirect effects was consistent with the multiple groups analysis. Conclusions The association between ADHD and adolescent RSB is restricted to youth with elevated comorbid conduct problems and reflects the contributions of comorbid marijuana use problems, and to a lesser extent alcohol use problems. Early identification and treatment of these comorbid conditions may be important for the prevention of negative sexual health outcomes among youth with ADHD. PMID:24813803

Transcriptional Changes in Canine Distemper Virus-Induced Demyelinating Leukoencephalitis Favor a Biphasic Mode of Demyelination

PubMed Central

Ulrich, Reiner; Puff, Christina; Wewetzer, Konstantin; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

2014-01-01

Canine distemper virus (CDV)-induced demyelinating leukoencephalitis in dogs (Canis familiaris) is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms “viral replication” and “humoral immune response” as well as down-regulated genes functionally related to “metabolite and energy generation”. PMID:24755553

Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination.

PubMed

Ulrich, Reiner; Puff, Christina; Wewetzer, Konstantin; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

2014-01-01

Canine distemper virus (CDV)-induced demyelinating leukoencephalitis in dogs (Canis familiaris) is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms "viral replication" and "humoral immune response" as well as down-regulated genes functionally related to "metabolite and energy generation".

Moderated mediation analysis: An illustration using the association of gender with delinquency and mental health.

PubMed

Miles, Jeremy N V; Kulesza, Magdalena; Ewing, Brett; Shih, Regina A; Tucker, Joan S; D'Amico, Elizabeth J

When researchers find an association between two variables, it is useful to evaluate the role of other constructs in this association. While assessing these mediation effects, it is important to determine if results are equal for different groups. It is possible that the strength of a mediation effect may differ for males and females, for example - such an effect is known as moderated mediation. Participants were 2532 adolescents from diverse ethnic/racial backgrounds and equally distributed across gender. The goal of this study was to investigate parental respect as a potential mediator of the relationship between gender and delinquency and mental health, and to determine whether observed mediation is moderated by gender. Parental respect mediated the association between gender and both delinquency and mental health. Specifically, parental respect was a protective factor against delinquency and mental health problems for both females and males. Demonstrated the process of estimating models in Lavaan, using two approaches (i.e. single group regression and multiple group regression model), and including covariates in both models.

Moderated mediation analysis: An illustration using the association of gender with delinquency and mental health

PubMed Central

Miles, Jeremy N.V.; Kulesza, Magdalena; Ewing, Brett; Shih, Regina A.; Tucker, Joan S.; D’Amico, Elizabeth J.

2015-01-01

Purpose When researchers find an association between two variables, it is useful to evaluate the role of other constructs in this association. While assessing these mediation effects, it is important to determine if results are equal for different groups. It is possible that the strength of a mediation effect may differ for males and females, for example – such an effect is known as moderated mediation. Design Participants were 2532 adolescents from diverse ethnic/racial backgrounds and equally distributed across gender. The goal of this study was to investigate parental respect as a potential mediator of the relationship between gender and delinquency and mental health, and to determine whether observed mediation is moderated by gender. Findings Parental respect mediated the association between gender and both delinquency and mental health. Specifically, parental respect was a protective factor against delinquency and mental health problems for both females and males. Practical implications Demonstrated the process of estimating models in Lavaan, using two approaches (i.e. single group regression and multiple group regression model), and including covariates in both models. PMID:26500722

Assessing natural direct and indirect effects through multiple pathways.

PubMed

Lange, Theis; Rasmussen, Mette; Thygesen, Lau Caspar

2014-02-15

Within the fields of epidemiology, interventions research and social sciences researchers are often faced with the challenge of decomposing the effect of an exposure into different causal pathways working through defined mediator variables. The goal of such analyses is often to understand the mechanisms of the system or to suggest possible interventions. The case of a single mediator, thus implying only 2 causal pathways (direct and indirect) from exposure to outcome, has been extensively studied. By using the framework of counterfactual variables, researchers have established theoretical properties and developed powerful tools. However, in practical problems, it is not uncommon to have several distinct causal pathways from exposure to outcome operating through different mediators. In this article, we suggest a widely applicable approach to quantifying and ranking different causal pathways. The approach is an extension of the natural effect models proposed by Lange et al. (Am J Epidemiol. 2012;176(3):190-195). By allowing the analysis of distinct multiple pathways, the suggested approach adds to the capabilities of modern mediation techniques. Furthermore, the approach can be implemented using standard software, and we have included with this article implementation examples using R (R Foundation for Statistical Computing, Vienna, Austria) and Stata software (StataCorp LP, College Station, Texas).

Stressors and Caregivers' Depression: Multiple Mediators of Self-Efficacy, Social Support, and Problem-Solving Skill.

PubMed

Tang, Fengyan; Jang, Heejung; Lingler, Jennifer; Tamres, Lisa K; Erlen, Judith A

2015-01-01

Caring for an older adult with memory loss is stressful. Caregiver stress could produce negative outcomes such as depression. Previous research is limited in examining multiple intermediate pathways from caregiver stress to depressive symptoms. This study addresses this limitation by examining the role of self-efficacy, social support, and problem solving in mediating the relationships between caregiver stressors and depressive symptoms. Using a sample of 91 family caregivers, we tested simultaneously multiple mediators between caregiver stressors and depression. Results indicate that self-efficacy mediated the pathway from daily hassles to depression. Findings point to the importance of improving self-efficacy in psychosocial interventions for caregivers of older adults with memory loss.

Mediators of adherence among adults with comorbid diabetes and depression: The role of self-efficacy and social support.

PubMed

Tovar, Elizabeth; Rayens, Mary Kay; Gokun, Yevgeniya; Clark, Michele

2015-11-01

Depression and diabetes have been linked in a variety of ways, and the presence of depression in those with diabetes can negatively affect adherence to care recommendations. A sample of 201 participants with Type 2 Diabetes completed a cross-sectional survey that assessed depressive symptoms, adherence, self-efficacy, social support, and personal characteristics. Multiple regression analysis was used to test whether self-efficacy and social support mediate the relationship between depressive symptoms and adherence. The findings suggest complete mediation via self-efficacy and some types of social support. Intervening to bolster self-efficacy and social support may decrease the negative effect of depression on adherence. © The Author(s) 2013.

DNA "nano-claw": logic-based autonomous cancer targeting and therapy.

PubMed

You, Mingxu; Peng, Lu; Shao, Na; Zhang, Liqin; Qiu, Liping; Cui, Cheng; Tan, Weihong

2014-01-29

Cell types, both healthy and diseased, can be classified by inventories of their cell-surface markers. Programmable analysis of multiple markers would enable clinicians to develop a comprehensive disease profile, leading to more accurate diagnosis and intervention. As a first step to accomplish this, we have designed a DNA-based device, called "Nano-Claw". Combining the special structure-switching properties of DNA aptamers with toehold-mediated strand displacement reactions, this claw is capable of performing autonomous logic-based analysis of multiple cancer cell-surface markers and, in response, producing a diagnostic signal and/or targeted photodynamic therapy. We anticipate that this design can be widely applied in facilitating basic biomedical research, accurate disease diagnosis, and effective therapy.

Preventing Cartilage Degeneration in Warfighters by Elucidating Novel Mechanisms Regulating Osteocyte-Mediated Perilacunar Bone Remodeling

DTIC Science & Technology

2016-10-01

sclerosis as in human PTOA. We also find that PLR is deregulated in human PTOA. We have made great strides in understanding the mechanosensitive regulation...conditions. We conducted an extremely thorough analysis of multiple experimental variables (loading regimen, mouse age, time course analysis) to better...Aim 3. Determine the extent of causality between defective PLR and cartilage degeneration in PTOA. A role for PLR in bone sclerosis

Authenticity and Relationship Satisfaction: Two Distinct Ways of Directing Power to Self-Esteem.

PubMed

Wang, Yi Nan

2015-01-01

Possessing power contributes to high self-esteem, but how power enhances self-esteem is still unknown. As power is associated with both self-oriented goals and social-responsibility goals, we proposed that power predicts self-esteem through two positive personal and interpersonal results: authenticity and relationship satisfaction. Three studies were carried out with a total of 505 Chinese participants, including college students and adults, who completed surveys that assessed personal power, self-esteem, authenticity, relationship satisfaction, communal orientation, and social desirability. Hierarchical multiple regression analyses demonstrated that power, authenticity, and relationship satisfaction each uniquely contributed to self-esteem. More importantly, multiple mediation analysis showed that authenticity and relationship satisfaction both mediated the effects of power on self-esteem, even when controlling for participants' communal orientation and social desirability. Our findings demonstrate that authenticity and relationship satisfaction represent two key mechanisms by which power is associated with self-esteem.

Authenticity and Relationship Satisfaction: Two Distinct Ways of Directing Power to Self-Esteem

PubMed Central

Wang, Yi Nan

2015-01-01

Possessing power contributes to high self-esteem, but how power enhances self-esteem is still unknown. As power is associated with both self-oriented goals and social-responsibility goals, we proposed that power predicts self-esteem through two positive personal and interpersonal results: authenticity and relationship satisfaction. Three studies were carried out with a total of 505 Chinese participants, including college students and adults, who completed surveys that assessed personal power, self-esteem, authenticity, relationship satisfaction, communal orientation, and social desirability. Hierarchical multiple regression analyses demonstrated that power, authenticity, and relationship satisfaction each uniquely contributed to self-esteem. More importantly, multiple mediation analysis showed that authenticity and relationship satisfaction both mediated the effects of power on self-esteem, even when controlling for participants’ communal orientation and social desirability. Our findings demonstrate that authenticity and relationship satisfaction represent two key mechanisms by which power is associated with self-esteem. PMID:26720814

Social Differentiation of Sun-Protection Behaviors: The Mediating Role of Cognitive Factors.

PubMed

Bocquier, Aurélie; Fressard, Lisa; Legleye, Stéphane; Verger, Pierre; Peretti-Watel, Patrick

2016-03-01

Adherence to sun-protection guidelines in developed countries is low, especially among people of low SES. Mechanisms underlying this social differentiation are poorly understood. This study aimed to examine the social differentiation of sun-protection behaviors and of two cognitive factors (knowledge about both sun health and behavioral risk factors for cancer) and to determine if these cognitive factors mediate the association between SES and sun-protection behaviors. Data came from the 2010 Baromètre Cancer survey (analyzed in 2014), a random cross-sectional telephone survey conducted among the French general population (n=3,359 individuals aged 15-75 years). First, bivariate associations between a composite individual SES indicator (based on education level, occupation, and income) and both sun-protection behaviors and cognitive factors were tested with chi-square tests and ANOVA. Then, confirmatory factor analysis and structural equation modeling were used to test the mediating role of cognitive factors with a multiple mediation model including four latent variables. In bivariate analyses, the individual SES indicator was positively associated with sun-protection behaviors and both cognitive factors. Multiple mediation analyses showed that both cognitive factors partially mediated the effect of individual SES on sun-protection behaviors. The overall proportion of mediated effects was 48%. The direct effect of SES remained significant. These results suggest that interventions aimed at modifying the knowledge and perceptions of people of low SES might help to reduce social differentiation of sun-protection behaviors. Further qualitative research is needed to better understand these cognitive factors and develop suitable prevention messages. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Cytokines and cytokine networks target neurons to modulate long-term potentiation.

PubMed

Prieto, G Aleph; Cotman, Carl W

2017-04-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytokines and cytokine networks target neurons to modulate long-term potentiation

PubMed Central

Prieto, G. Aleph; Cotman, Carl W.

2017-01-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. PMID:28377062

Affective mediators of a physical activity intervention for depression in multiple sclerosis.

PubMed

Kratz, Anna L; Ehde, Dawn M; Bombardier, Charles H

2014-02-01

Previous analyses showed that a telephone-based intervention to increase physical activity in individuals with multiple sclerosis (MS) and depression resulted in significantly improved depressive symptoms compared to a wait-list control group. The aim of this study was to test positive affect and negative affect as mediators of the effect of the physical activity counseling on depressive symptoms. Ninety-two adults with MS, who met diagnostic criteria for either major depression or dysthymia and who reported low levels of physical activity, were randomized 1:1 to a 12-week telephone-based motivational interviewing (MI) intervention to improve physical activity (n = 44) or to a 12-week wait-list control group (n = 48). Self-reported positive and negative affect, physical activity, and depressive symptoms were gathered at baseline and postintervention. Path-analysis was used to test whether positive affect and negative affect mediated the positive effects of the intervention on depressive symptoms. Both positive and negative affect were significant mediators of the effects of the intervention on depressive symptoms; however, only positive affect mediated the association between changes in physical activity and improved depressive symptoms. Findings support physical activity and positive affect as key mediators of the MI treatment effect on improved mood. Decreases in negative affect were also evident in the treatment group, but were not related to improved physical activity. Findings may suggest the use of exercise-based interventions in conjunction with treatments that specifically target negative affective mechanisms for depression. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Basic leucine zipper transcription factor SlbZIP1 mediates salt and drought stress tolerance in tomato.

PubMed

Zhu, Mingku; Meng, Xiaoqing; Cai, Jing; Li, Ge; Dong, Tingting; Li, Zongyun

2018-05-08

Basic region/leucine zipper (bZIP) transcription factors perform as crucial regulators in ABA-mediated stress response in plants. Nevertheless, the functions for most bZIP family members in tomato remain to be deciphered. Here we examined the functional characterization of SlbZIP1 under salt and drought stresses in tomato. Silencing of SlbZIP1 in tomato resulted in reduced expression of multiple ABA biosynthesis- and signal transduction-related genes in transgenic plants. In stress assays, SlbZIP1-RNAi transgenic plants exhibited reduced tolerance to salt and drought stresses compared with WT plants, as are evaluated by multiple physiological parameters associated with stress responses, such as decreased ABA, chlorophyll contents and CAT activity, and increased MDA content. In addition, RNA-seq analysis of transgenic plants revealed that the transcription levels of multiple genes encoding defense proteins related to responses to abiotic stress (e.g. endochitinase, peroxidases, and lipid transfer proteins) and biotic stress (e.g. pathogenesis-related proteins) were downregulated in SlbZIP1-RNAi plants, suggesting that SlbZIP1 plays a role in regulating the genes related to biotic and abiotic stress response. Collectively, the data suggest that SlbZIP1 exerts an essential role in salt and drought stress tolerance through modulating an ABA-mediated pathway, and SlbZIP1 may hold potential applications in the engineering of salt- and drought-tolerant tomato cultivars.

Anger and depression: evidence of a possible mediating role for rumination.

PubMed

Balsamo, Michela

2010-02-01

Tendency to ruminate may mediate the relationship between anger and depression. In this preliminary study, 353 Italian community participants completed the State-Trait Anger Expression Inventory-2, the Padua Inventory's Tendency to Doubt and to Ruminate subscale, and the Beck Depression Inventory-II. Trait anger and depression were expected to have a positive relationship, and separate relationships with the tendency to ruminate. Theoretically, a new hypothesis was that the tendency to ruminate would mediate the relationship between depression and anger. Zero-order and partial correlations and a path analysis based on Baron and Kenny's method for calculating multiple regression analyses were calculated. Consistent with the hypotheses, anger and depression were strongly associated; the tendency to ruminate was significantly associated with both anger and depression; and the mediation model fit the data. Behaviors related to the tendency to ruminate could help to explain how depression is related to anger.

The relationship between parental mediation and Internet addiction among adolescents, and the association with cyberbullying and depression.

PubMed

Chang, Fong-Ching; Chiu, Chiung-Hui; Miao, Nae-Fang; Chen, Ping-Hung; Lee, Ching-Mei; Chiang, Jeng-Tung; Pan, Ying-Chun

2015-02-01

This study examined the relationships between parental mediation and Internet addiction, and the connections to cyberbullying, substance use, and depression among adolescents. The study involved 1808 junior high school students who completed a questionnaire in Taiwan in 2013. Multiple logistic regression analysis results showed that adolescents who perceived lower levels of parental attachment were more likely to experience Internet addiction, cyberbullying, smoking, and depression, while adolescents who reported higher levels of parental restrictive mediation were less likely to experience Internet addiction or to engage in cyberbullying. Adolescent Internet addiction was associated with cyberbullying victimization/perpetration, smoking, consumption of alcohol, and depression. Internet addiction by adolescents was associated with cyberbullying, substance use and depression, while parental restrictive mediation was associated with reductions in adolescent Internet addiction and cyberbullying. Copyright © 2014 Elsevier Inc. All rights reserved.

Collective-efficacy as a mediator of the relationship of leaders' personality traits and team performance: A cross-level analysis.

PubMed

Li, Xiaoshan; Zhou, Mingjie; Zhao, Na; Zhang, Shanshan; Zhang, Jianxin

2015-06-01

The relationship between a leader's personality and his team's performance has been established in organisational research, but the underlying process and mechanism responsible for this effect have not been fully explored. Both the traditional multiple linear regression and the multilevel structural equation model approaches were used in this study to test a proposed mediating model of subordinates' perception of collective efficacy between leader personality and team performance. The results show that the team leader's extraversion and conscientiousness personality traits were related positively to both the team-average (individual) perception of collective efficacy and team performance, and the collective efficacy mediated the relationship of the leader's personality traits and team performance. This study also discusses how Chinese cultural elements play a role in such a mediating model. © 2014 International Union of Psychological Science.

Mediation and moderation of the association between cynical hostility and systolic blood pressure in low-income women.

PubMed

Versey, H Shellae; Kaplan, George A

2012-04-01

Hostility may be related to risk factors for cardiovascular disease (CVD), such as blood pressure. However, the process by which hostility affects blood pressure is not fully understood. The current study sought to evaluate abdominal obesity (waist-to-hip ratio [WHR]) as a potential mediator and modifier of the relationship between cynical hostility and systolic blood pressure (SBP) in a group of disadvantaged women. Path analysis and multiple regression models were used to identify mediating and moderating pathways in the relationship between cynical hostility and SBP. Results indicate a significant interaction between WHR and cynical hostility. WHR was a partial mediator and significant moderator of the association between hostility and blood pressure. These findings highlight the potential importance of examining abdominal obesity and psychosocial factors as conjunctive determinants of CVD and risk factors for related metabolic conditions.

Mediating Effects of Global Negative Effect Expectancies on the Association between Problematic Cannabis Use and Social Anxiety.

PubMed

Di Blasi, Maria; Cavani, Paola; Pavia, Laura; Tosto, Crispino; La Grutta, Sabina; Lo Baido, Rosa; Giordano, Cecilia; Schimmenti, Adriano

2017-01-01

The relationship between social anxiety (SA) and cannabis use among adolescents and young adults is a highly debated topic. In this cross-sectional study, we tested whether cannabis use expectancies mediated the association between SA and cannabis use severity in a sample of 343 young adults (74.3% male) who used cannabis. They completed self-report measures for the screening of problematic cannabis use (Cannabis Use Problems Identification Test) and SA symptoms (Social Interaction Anxiety Scale and Social Phobia Scale). A multiple mediation analysis was used to test whether marijuana effect expectancies mediate SA effect on problematic cannabis use. SA was negatively associated with cannabis use severity in this sample, and we found evidence that cannabis use expectancies fully mediated this relationship. Specifically, global negative effect expectancies influence the relationship between SA and problematic cannabis use. These findings may inform current prevention strategies and clinical intervention for young adults who use cannabis.

Children's appraisals as mediators of the relationship between domestic violence and child adjustment.

PubMed

Fortin, Andrée; Doucet, Martin; Damant, Dominique

2011-01-01

This study examines the relationships among variables that were likely to mediate the effects of exposure to domestic violence on children's internalizing problems (i.e., children's appraisals of domestic violence and their perceptions of family relationships). The study was conducted with 79 children exposed to domestic violence, including 41 boys and 38 girls, aged between 9 and 12 years old. Indicators used for children's appraisals of violence were attribution of blame and perceived threat. Children's perceptions of family relationships were based on their levels of parentification and the degree of their loyalty conflicts. A path analysis was used to verify the predictive model's pathways and to test the multiple mediator effects. Findings confirm the contribution of mediating variables and also reflect the association between self-blame and children's parentification. The results stress the relevance of evaluating the combined role of different potential mediators to provide a better understanding of the impact of domestic violence on children.

On the association between sexual attraction and adolescent risk behavior involvement: Examining mediation and moderation.

PubMed

Busseri, Michael A; Willoughby, Teena; Chalmers, Heather; Bogaert, Anthony F

2008-01-01

On the basis of a large-scale survey of high-school youth, the authors compared adolescents reporting exclusively heterosexual, mostly heterosexual, bisexual, and predominately same-sex attraction based on high-risk involvement across a range of risk behaviors. Bisexual and same-sex attracted groups were characterized by heightened high-risk involvement relative to the other two groups. Mediation analysis was used to determine whether these group disparities were explained by a set of normative predictive factors spanning multiple life domains. Differences among a combined exclusively/mostly heterosexual attraction group and both the bisexual and same-sex attraction groups were attenuated (66% and 50%, respectively) after incorporating the hypothesized intervening predictive factors, providing evidence of partial mediation. Primary mediators included intrapersonal (attitudes toward risk-taking; academic orientation), interpersonal (peer victimization; parental relationships; unstructured activities), and environmental (substance availability) factors. Mediation results were consistent across participant age and sex. Implications, limitations, and directions for future research are discussed. Copyright (c) 2008 APA.

An Exploration of the Mediators Between Childhood Maltreatment and Intimate Partner Violence.

PubMed

Smyth, Elizabeth J; Gardner, Frank L; Marks, Donald R; Moore, Zella E

2017-08-01

Intimate partner violence (IPV) is associated with numerous long-term consequences and warrants significant clinical attention. Recent theoretical models and empirical research have suggested that several factors play a role in the development of IPV perpetration, including childhood maltreatment, early maladaptive schemas, anger, and difficulties in emotion regulation. This study investigated the relationship between childhood maltreatment and IPV, specifically examining the mediation of this relationship by several variables thought to be related to this pernicious problem, including early maladaptive schemas, the experience of anger, and emotion regulation difficulties. In a young adult collegiate sample of 110 women in relationships, results of a bootstrapped multiple mediation analysis supported the hypothesis that childhood maltreatment predicted physical aggression within intimate partner relationships and found that the total indirect effect of childhood maltreatment on physical aggression through the 3 proposed mediators was significant. However, consistent with recent empirical findings, only difficulties in emotion regulation significantly mediated the relationship between childhood maltreatment and physical aggression within the sample.

Do sophisticated epistemic beliefs predict meaningful learning? Findings from a structural equation model of undergraduate biology learning

NASA Astrophysics Data System (ADS)

Lee, Silvia Wen-Yu; Liang, Jyh-Chong; Tsai, Chin-Chung

2016-10-01

This study investigated the relationships among college students' epistemic beliefs in biology (EBB), conceptions of learning biology (COLB), and strategies of learning biology (SLB). EBB includes four dimensions, namely 'multiple-source,' 'uncertainty,' 'development,' and 'justification.' COLB is further divided into 'constructivist' and 'reproductive' conceptions, while SLB represents deep strategies and surface learning strategies. Questionnaire responses were gathered from 303 college students. The results of the confirmatory factor analysis and structural equation modelling showed acceptable model fits. Mediation testing further revealed two paths with complete mediation. In sum, students' epistemic beliefs of 'uncertainty' and 'justification' in biology were statistically significant in explaining the constructivist and reproductive COLB, respectively; and 'uncertainty' was statistically significant in explaining the deep SLB as well. The results of mediation testing further revealed that 'uncertainty' predicted surface strategies through the mediation of 'reproductive' conceptions; and the relationship between 'justification' and deep strategies was mediated by 'constructivist' COLB. This study provides evidence for the essential roles some epistemic beliefs play in predicting students' learning.

Mediating Effects of Global Negative Effect Expectancies on the Association between Problematic Cannabis Use and Social Anxiety

PubMed Central

Di Blasi, Maria; Cavani, Paola; Pavia, Laura; Tosto, Crispino; La Grutta, Sabina; Lo Baido, Rosa; Giordano, Cecilia; Schimmenti, Adriano

2017-01-01

The relationship between social anxiety (SA) and cannabis use among adolescents and young adults is a highly debated topic. In this cross-sectional study, we tested whether cannabis use expectancies mediated the association between SA and cannabis use severity in a sample of 343 young adults (74.3% male) who used cannabis. They completed self-report measures for the screening of problematic cannabis use (Cannabis Use Problems Identification Test) and SA symptoms (Social Interaction Anxiety Scale and Social Phobia Scale). A multiple mediation analysis was used to test whether marijuana effect expectancies mediate SA effect on problematic cannabis use. SA was negatively associated with cannabis use severity in this sample, and we found evidence that cannabis use expectancies fully mediated this relationship. Specifically, global negative effect expectancies influence the relationship between SA and problematic cannabis use. These findings may inform current prevention strategies and clinical intervention for young adults who use cannabis. PMID:29213247

Stressors and Caregivers’ Depression: Multiple Mediators of Self-Efficacy, Social Support, and Problem-solving Skill

PubMed Central

Tang, Fengyan; Jang, Heejung; Lingler, Jennifer; Tamres, Lisa K.; Erlen, Judith A.

2016-01-01

Caring for an older adult with memory loss is stressful. Caregiver stress could produce negative outcomes such as depression. Previous research is limited in examining multiple intermediate pathways from caregiver stress to depressive symptoms. This study addresses this limitation by examining the role of self-efficacy, social support, and problem-solving in mediating the relationships between caregiver stressors and depressive symptoms. Using a sample of 91 family caregivers, we tested simultaneously multiple mediators between caregiver stressors and depression. Results indicate that self-efficacy mediated the pathway from daily hassles to depression. Findings point to the importance of improving self-efficacy in psychosocial interventions for caregivers of older adults with memory loss. PMID:26317766

Lipidomics of oxidized polyunsaturated fatty acids

PubMed Central

Massey, Karen A.; Nicolaou, Anna

2013-01-01

Lipid mediators are produced from the oxidation of polyunsaturated fatty acids through enzymatic and free radical-mediated reactions. When subject to oxygenation via cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases, polyunsaturated fatty acids give rise to an array of metabolites including eicosanoids, docosanoids, and octadecanoids. These potent bioactive lipids are involved in many biochemical and signaling pathways, with inflammation being of particular importance. Moreover, because they are produced by more than one pathway and substrate, and are present in a variety of biological milieus, their analysis is not always possible with conventional assays. Liquid chromatography coupled to electrospray mass spectrometry offers a versatile and sensitive approach for the analysis of bioactive lipids, allowing specific and accurate quantitation of multiple species present in the same sample. Here we explain the principles of this approach to mediator lipidomics and present detailed protocols for the assay of enzymatically produced oxygenated metabolites of polyunsaturated fatty acids that can be tailored to answer biological questions or facilitate assessment of nutritional and pharmacological interventions. PMID:22940496

Improving quality-of-life outcomes for patients with cancer through mediating effects of depressive symptoms and functional status: a three-path mediation model.

PubMed

Hsu, Mei-Chi; Tu, Chun-Hsien

2014-09-01

To test a hypothetical three-path mediation model evaluating the effects of functional status and depressive symptoms on the relationship between fatigue and quality of life in patients with cancer on the basis of the Theory of Unpleasant Symptoms. Patients with cancer often experience two or more concurrent, interrelated, mutually influential symptoms. Multiple unpleasant symptoms that have been proposed as mediating variables affecting quality of life in a model proposed in recent cancer studies are scanty. This study was a cross-sectional, descriptive, correlational design. Three hundred and twenty-six patients with cancer from oncology clinics were recruited in Taiwan between 2010-2011. Mediation models were tested and confirmed by applying structural modelling using Analysis of Moment Structures and the joint significance test. Fatigue affects patient quality of life directly or indirectly through functional status and depressive symptoms. These two mediating variables exhibited direct effects on quality of life. A path analysis approach revealed that 47·28 and 67·70% of the total effects of functional status and depressive symptoms, respectively, on the quality-of-life mediation models are attributable to 29·6 and 44·7% of the total effects between fatigue and quality of life, which mediated through two mediators, respectively. Quality of life may be enhanced by simultaneously improving physiological and psychological factors. An understanding of mediating effects is valuable in nursing care of patients with cancer, particularly in the early phase of treatment or in newly diagnosed stages I-III or recently treated patients with cancer in different disease stages. © 2013 John Wiley & Sons Ltd.

Illness representations as mediators of the relationship between dispositional optimism and depression in patients with chronic tinnitus: a cross-sectional study.

PubMed

Vollmann, Manja; Scharloo, Margreet; Langguth, Berthold; Kalkouskaya, Natallia; Salewski, Christel

2013-01-01

Both dispositional optimism and illness representations are related to psychological health in chronic patients. In a group of chronic tinnitus sufferers, the interplay between these two variables was examined. Specifically, it was tested to what extent the relationship between dispositional optimism and depression is mediated by more positive illness representations. The study had a cross-sectional design. One hundred and eighteen patients diagnosed with chronic tinnitus completed questionnaires assessing optimism (Life Orientation Test-Revised [LOT-R]), illness representations (Illness Perceptions Questionnaire-Revised [IPQ-R]) and depression (Hospital Anxiety and Depression Scale [HADS]). Correlation analysis showed that optimism was associated with more positive illness representations and lower levels of depression. Simple mediation analyses revealed that the relationship between optimism and depression was partially mediated by the illness representation dimensions consequences, treatment control, coherence, emotional representations and internal causes. A multiple mediation analysis indicated that the total mediation effect of illness representations is particularly due to the dimension consequences. Optimism influences depression in tinnitus patients both directly and indirectly. The indirect effect indicates that optimism is associated with more positive tinnitus-specific illness representations which, in turn, are related to less depression. These findings contribute to a better understanding of the interplay between generalised expectancies, illness-specific perceptions and psychological adjustment to medical conditions.

Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis.

PubMed

Solanki, Hitendra S; Advani, Jayshree; Khan, Aafaque Ahmad; Radhakrishnan, Aneesha; Sahasrabuddhe, Nandini A; Pinto, Sneha M; Chang, Xiaofei; Prasad, Thottethodi Subrahmanya Keshava; Mathur, Premendu Prakash; Sidransky, David; Gowda, Harsha; Chatterjee, Aditi

2017-08-01

Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke. Using high resolution Orbitrap Velos mass spectrometer, we identified the hyperphosphorylation of 493 sites, which corresponds to 341 proteins and 195 hypophosphorylated sites, mapping to 142 proteins upon smoke exposure (2.0-fold change). We report differential phosphorylation of multiple kinases, including PAK6, EPHA4, LYN, mitogen-activated protein kinase, and phosphatases, including TMEM55B, PTPN14, TIGAR, among others, in response to chronic cigarette smoke exposure. Bioinformatics analysis revealed that the molecules differentially phosphorylated upon chronic exposure of cigarette smoke are associated with PI3K/AKT/mTOR and CDC42-PAK signaling pathways. These signaling networks are involved in multiple cellular processes, including cell polarity, cytoskeletal remodeling, cellular migration, protein synthesis, autophagy, and apoptosis. The present study contributes to emerging proteomics insights on cigarette smoke mediated global signaling in lung cells, which in turn may aid in development of precision medicine therapeutics and postgenomics biomarkers.

Changes in illness perceptions mediated the effect of cognitive behavioural therapy in severe functional somatic syndromes.

PubMed

Christensen, Sara Sletten; Frostholm, Lisbeth; Ørnbøl, Eva; Schröder, Andreas

2015-04-01

Although there is substantial evidence that cognitive behavioural therapy alleviates symptoms in functional somatic syndromes, the mechanisms of change are less investigated. This study examined whether changes in illness perceptions mediated the effect of cognitive behavioural therapy. We analysed additional data from a randomised controlled trial comparing completers of cognitive behavioural group therapy (46 patients) to an enhanced usual care group (66 patients). Proposed mediators (illness perceptions) and primary (physical health) and secondary (somatic symptoms and illness worry) outcomes were assessed by means of questionnaires at referral, baseline, end of treatment, and 10 and 16 months after randomisation. Multiple mediation analysis determined whether (1) changes in specific illness perceptions during treatment mediated the effect of cognitive behavioural therapy (primary analysis), and (2) whether changes in illness perceptions during the whole trial period were associated with improved outcome (secondary analysis). Improvements in illness perceptions during treatment partially mediated the effect of cognitive behavioural therapy on physical health one year after treatment (sum of indirect effects 1.556, BCa 95% CI (0.006; 3.620)). Improving perceived control was particularly important. Changes in illness perceptions from baseline to 16 months after randomisation were associated with clinically meaningful improvements in physical health, somatic symptoms and illness worry during the same period. Our results suggest that changing patients' illness perceptions is an important process in cognitive behavioural therapy for functional somatic syndromes. Challenging patients' own understanding of their illness may hence be a key element of successful treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Verbal and Visual Memory Impairments in Bipolar I and II Disorder.

PubMed

Ha, Tae Hyon; Kim, Ji Sun; Chang, Jae Seung; Oh, Sung Hee; Her, Ju Young; Cho, Hyun Sang; Park, Tae Sung; Shin, Soon Young; Ha, Kyooseob

2012-12-01

To compare verbal and visual memory performances between patients with bipolar I disorder (BD I) and patients with bipolar II disorder (BD II) and to determine whether memory deficits were mediated by impaired organizational strategies. Performances on the Korean-California Verbal Learning Test (K-CVLT) and the Rey-Osterrieth Complex Figure Test (ROCF) in 37 patients with BD I, 46 patients with BD II and 42 healthy subjects were compared. Mediating effects of impaired organization strategies on poor delayed recall was tested by comparing direct and mediated models using multiple regression analysis. Both patients groups recalled fewer words and figure components and showed lower Semantic Clustering compared to controls. Verbal memory impairment was partly mediated by difficulties in Semantic Clustering in both subtypes, whereas the mediating effect of Organization deficit on the visual memory impairment was present only in BD I. In all mediated models, group differences in delayed recall remained significant. Our findings suggest that memory impairment may be one of the fundamental cognitive deficits in bipolar disorders and that executive dysfunctions can exert an additional influence on memory impairments.

Inverse odds ratio-weighted estimation for causal mediation analysis.

PubMed

Tchetgen Tchetgen, Eric J

2013-11-20

An important scientific goal of studies in the health and social sciences is increasingly to determine to what extent the total effect of a point exposure is mediated by an intermediate variable on the causal pathway between the exposure and the outcome. A causal framework has recently been proposed for mediation analysis, which gives rise to new definitions, formal identification results and novel estimators of direct and indirect effects. In the present paper, the author describes a new inverse odds ratio-weighted approach to estimate so-called natural direct and indirect effects. The approach, which uses as a weight the inverse of an estimate of the odds ratio function relating the exposure and the mediator, is universal in that it can be used to decompose total effects in a number of regression models commonly used in practice. Specifically, the approach may be used for effect decomposition in generalized linear models with a nonlinear link function, and in a number of other commonly used models such as the Cox proportional hazards regression for a survival outcome. The approach is simple and can be implemented in standard software provided a weight can be specified for each observation. An additional advantage of the method is that it easily incorporates multiple mediators of a categorical, discrete or continuous nature. Copyright © 2013 John Wiley & Sons, Ltd.

Racial discrimination, binge drinking, and negative drinking consequences among black college students: serial mediation by depressive symptoms and coping motives.

PubMed

Desalu, Jessica M; Kim, Jueun; Zaso, Michelle J; Corriders, Sydnee R; Loury, Jacoby A; Minter, Monique L; Park, Aesoon

2017-09-21

Experiences of racial discrimination have been associated with diverse negative health outcomes among racial minorities. However, extant findings of the association between racial discrimination and alcohol behaviors among Black college students are mixed. The current study examined mediating roles of depressive symptoms and coping drinking motives in the association of perceived racial discrimination with binge drinking and negative drinking consequences. Data were obtained from a cross-sectional study of Black college students attending a predominantly White institution in the northeastern US (N = 251, 66% female, mean age = 20 years). Results from path analysis showed that, when potential mediators were not considered, perceived racial discrimination was positively associated with negative drinking consequences but not frequency of binge drinking. Serial multiple mediation analysis showed that depressive symptoms and in turn coping drinking motives partially mediated the associations of perceived racial discrimination with both binge drinking frequency and negative drinking consequences (after controlling for sex, age, and negative life events). Perceived racial discrimination is directly associated with experiences of alcohol-related problems, but not binge drinking behaviors among Black college students. Affective responses to perceived racial discrimination experiences and drinking to cope may serve as risk mechanisms for alcohol-related problems in this population. Implications for prevention and intervention efforts are discussed.

Relationships Between Stress, Negative Emotions, Resilience, and Smoking: Testing a Moderated Mediation Model.

PubMed

Wang, Yan; Chen, Xinguang; Gong, Jie; Yan, Yaqiong

2016-01-01

More effective tobacco prevention and cessation programs require in-depth understanding of the mechanism by which multiple factors interact with each other to affect smoking behaviors. Stress has long been recognized as a risk factor for smoking. However, the underlying mediation and moderation mechanisms are far from clear. The purpose of this study was to examine the role of negative emotions in mediating the link between stress and smoking and whether this indirect link was modified by resilience. Survey data were collected using audio computer-assisted self-interview (ACASI) from a large random sample of urban residents (n = 1249, mean age = 35.1, 45.3% male) in Wuhan, China. Perceived stress, negative emotions (anxiety, depression), resilience were measured with reliable instruments also validated in China. Self-reported smoking was validated with exhaled carbon monoxide. Mediation analysis indicated that two negative emotions fully mediated the link between stress and intensity of smoking (assessed by number of cigarettes smoked per day, effect =.082 for anxiety and.083 for depression) and nicotine dependence (assessed by DSM-IV standard, effect =.134 for anxiety and.207 for depression). Moderated mediation analysis demonstrated that the mediation effects of negative emotions were negatively associated with resilience. Results suggest resilience interacts with stress and negative emotions to affect the risk of tobacco use and nicotine dependence among Chinese adults. Further research with longitudinal data is needed to verify the findings of this study and to estimate the effect size of resilience in tobacco intervention and cessation programs.

Work–Family Conflict and Mental Health Among Female Employees: A Sequential Mediation Model via Negative Affect and Perceived Stress

PubMed Central

Zhou, Shiyi; Da, Shu; Guo, Heng; Zhang, Xichao

2018-01-01

After the implementation of the universal two-child policy in 2016, more and more working women have found themselves caught in the dilemma of whether to raise a baby or be promoted, which exacerbates work–family conflicts among Chinese women. Few studies have examined the mediating effect of negative affect. The present study combined the conservation of resources model and affective events theory to examine the sequential mediating effect of negative affect and perceived stress in the relationship between work–family conflict and mental health. A valid sample of 351 full-time Chinese female employees was recruited in this study, and participants voluntarily answered online questionnaires. Pearson correlation analysis, structural equation modeling, and multiple mediation analysis were used to examine the relationships between work–family conflict, negative affect, perceived stress, and mental health in full-time female employees. We found that women’s perceptions of both work-to-family conflict and family-to-work conflict were significant negatively related to mental health. Additionally, the results showed that negative affect and perceived stress were negatively correlated with mental health. The 95% confidence intervals indicated the sequential mediating effect of negative affect and stress in the relationship between work–family conflict and mental health was significant, which supported the hypothesized sequential mediation model. The findings suggest that work–family conflicts affected the level of self-reported mental health, and this relationship functioned through the two sequential mediators of negative affect and perceived stress. PMID:29719522

Work-Family Conflict and Mental Health Among Female Employees: A Sequential Mediation Model via Negative Affect and Perceived Stress.

PubMed

Zhou, Shiyi; Da, Shu; Guo, Heng; Zhang, Xichao

2018-01-01

After the implementation of the universal two-child policy in 2016, more and more working women have found themselves caught in the dilemma of whether to raise a baby or be promoted, which exacerbates work-family conflicts among Chinese women. Few studies have examined the mediating effect of negative affect. The present study combined the conservation of resources model and affective events theory to examine the sequential mediating effect of negative affect and perceived stress in the relationship between work-family conflict and mental health. A valid sample of 351 full-time Chinese female employees was recruited in this study, and participants voluntarily answered online questionnaires. Pearson correlation analysis, structural equation modeling, and multiple mediation analysis were used to examine the relationships between work-family conflict, negative affect, perceived stress, and mental health in full-time female employees. We found that women's perceptions of both work-to-family conflict and family-to-work conflict were significant negatively related to mental health. Additionally, the results showed that negative affect and perceived stress were negatively correlated with mental health. The 95% confidence intervals indicated the sequential mediating effect of negative affect and stress in the relationship between work-family conflict and mental health was significant, which supported the hypothesized sequential mediation model. The findings suggest that work-family conflicts affected the level of self-reported mental health, and this relationship functioned through the two sequential mediators of negative affect and perceived stress.

Gender-Related Differential Effects of Obesity on Health-Related Quality of Life via Obesity-Related Comorbidities: A Mediation Analysis of a French Nationwide Survey.

PubMed

Audureau, Etienne; Pouchot, Jacques; Coste, Joël

2016-05-01

Negative effects of obesity on health-related quality of life (HRQoL) have been reported, especially in women, but the relative contribution of cardiometabolic and other obesity-related comorbidities to such effects remains unclear. Our objective was to model the association by sex between body mass index and HRQoL and to precisely quantify the indirect effects mediated by obesity-related comorbidities. Data were drawn from the latest French Decennial Health Survey, a nationwide cross-sectional study conducted in 2003 (21 239 adults aged 25-64 years analyzed). HRQoL was measured by the 36-item short-form health survey questionnaire. A mediation analysis based on the counterfactual framework was performed to quantify the proportion of obesity effects on HRQoL mediated by related comorbidities, including cardiometabolic risk factors (diabetes mellitus, hypertension, dyslipidemia) and diseases (ischemic heart disease, cerebrovascular, and peripheral vascular disease), musculoskeletal disorders, and asthma. After multiple linear regression, inverse associations were found between increasing body mass index category and physically oriented and most mentally oriented 36-item short-form health survey dimensions, with evidence of greater effects in women. Mediation analysis revealed that obesity effects were significantly mediated by several comorbidities, more apparently in men (eg, proportion of obesity class II total effect mediated via cardiometabolic factors: general health 27.0% [men] versus 13.6% [women]; proportion of obesity class II total effect mediated via total count of comorbidities: physical functioning 17.8% [men] versus 7.7% [women] and general health 37.1% [men] versus 20.3% [women]). Women have a greater overall impact of obesity on HRQoL, but with proportionally lower effects mediated by cardiometabolic and other obesity-related conditions, suggesting the possible role of other specific psychosocial processes. © 2016 American Heart Association, Inc.

Methods for the Analysis of Protein Phosphorylation-Mediated Cellular Signaling Networks

NASA Astrophysics Data System (ADS)

White, Forest M.; Wolf-Yadlin, Alejandro

2016-06-01

Protein phosphorylation-mediated cellular signaling networks regulate almost all aspects of cell biology, including the responses to cellular stimulation and environmental alterations. These networks are highly complex and comprise hundreds of proteins and potentially thousands of phosphorylation sites. Multiple analytical methods have been developed over the past several decades to identify proteins and protein phosphorylation sites regulating cellular signaling, and to quantify the dynamic response of these sites to different cellular stimulation. Here we provide an overview of these methods, including the fundamental principles governing each method, their relative strengths and weaknesses, and some examples of how each method has been applied to the analysis of complex signaling networks. When applied correctly, each of these techniques can provide insight into the topology, dynamics, and regulation of protein phosphorylation signaling networks.

ADHD and risky sexual behavior in adolescents: conduct problems and substance use as mediators of risk.

PubMed

Sarver, Dustin E; McCart, Michael R; Sheidow, Ashli J; Letourneau, Elizabeth J

2014-12-01

Recent studies have linked attention-deficit/hyperactivity disorder (ADHD) to elevated rates of risky sexual behavior (RSB) in adult samples. The current study tested whether ADHD symptoms were associated with RSB among adolescents, and examined comorbid conduct problems and problematic substance use as joint mediators of this association. ADHD symptoms, conduct problems (oppositional defiant disorder/conduct disorder symptoms), problematic alcohol use (alcohol use disorder symptoms, alcohol use frequency), problematic marijuana use (marijuana use disorder symptoms, marijuana use frequency), and RSB were assessed among an ethnically diverse cross-sectional sample of adolescents (N = 115; mean age = 14.9 years) involved in the juvenile justice system. Bootstrapped mediation models revealed an initial association between ADHD symptoms and RSB that was accounted for fully by the influence of problematic alcohol and marijuana use, but not conduct problems. A follow-up multiple groups mediation analysis demonstrated that the relationship between ADHD symptoms and RSB emerged only among youth with clinically elevated conduct problems, and that problematic marijuana use fully accounted for this relationship. Hyperactive/impulsive, but not inattentive, symptoms were related to RSB, although the pattern of indirect effects was consistent with the multiple groups analysis. The association between ADHD and adolescent RSB is restricted to youth with elevated comorbid conduct problems and reflects the contributions of comorbid marijuana use problems, and to a lesser extent alcohol use problems. Early identification and treatment of these comorbid conditions may be important for the prevention of negative sexual health outcomes among youth with ADHD. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

Why are Tailored Messages More Effective? A Multiple Mediation Analysis of a Breast Cancer Screening Intervention.

PubMed

Jensen, Jakob D; King, Andy J; Carcioppolo, Nicholas; Davis, LaShara

2012-10-01

Past research has found that tailoring increases the persuasive effectiveness of a message. However, the observed effect has been small and the explanatory mechanism remains unknown. To address these shortcomings, a tailoring software program was created that personalized breast cancer screening pamphlets according to risk, health belief model constructs, and visual preference. Women aged 40 and older ( N = 119) participated in a 2 (tailored vs. stock message) × 2 (charts/graphs vs. illustrated visuals) × 3 (nested replications of the visuals) experiment. Participants provided with tailored illustrated pamphlets expressed greater breast cancer screening intentions than those provided with other pamphlets. In a test of 10 different mediators, perceived message relevance was found to fully mediate the tailoring × visual interaction.

Cognitive behavioural therapy for MS-related fatigue explained: A longitudinal mediation analysis.

PubMed

van den Akker, L E; Beckerman, H; Collette, E H; Knoop, H; Bleijenberg, G; Twisk, J W; Dekker, J; de Groot, V

2018-03-01

Cognitive behavioural therapy (CBT) effectively reduces fatigue directly following treatment in patients with Multiple Sclerosis (MS), but little is known about the process of change during and after CBT. Additional analysis of a randomized clinical trial. To investigate which psychological factors mediate change in fatigue during and after CBT. TREFAMS-CBT studied the effectiveness of a 16-week CBT treatment for MS-related fatigue. Ninety-one patients were randomized (44 to CBT, 47 to the MS-nurse consultations). Mediation during CBT treatment was studied using assessments at baseline, 8 and 16weeks. Mediation of the change in fatigue from post-treatment to follow-up was studied separately using assessments at 16, 26 and 52weeks. Proposed mediators were: changes in illness cognitions, general self-efficacy, coping styles, daytime sleepiness, concentration and physical activity, fear of disease progression, fatigue perceptions, depression and physical functioning. Mediators were separately analysed according to the product-of-coefficients approach. Confidence intervals were calculated with a bootstrap procedure. During treatment the decrease in fatigue brought on by CBT was mediated by improved fatigue perceptions, increased physical activity, less sleepiness, less helplessness, and improved physical functioning. Post-treatment increases in fatigue levels were mediated by reduced physical activity, reduced concentration, and increased sleepiness. These results suggests that focusing on improving fatigue perceptions, perceived physical activity, daytime sleepiness, helplessness, and physical functioning may further improve the effectiveness of CBT for fatigue in patients with MS. Maintenance of treatment effects may be obtained by focusing on improving physical activity, concentration and sleepiness. Copyright © 2018 Elsevier Inc. All rights reserved.

Shrimp miR-12 Suppresses White Spot Syndrome Virus Infection by Synchronously Triggering Antiviral Phagocytosis and Apoptosis Pathways

PubMed Central

Shu, Le; Zhang, Xiaobo

2017-01-01

Growing evidence has indicated that the innate immune system can be regulated by microRNAs (miRNAs). However, the mechanism underlying miRNA-mediated simultaneous activation of multiple immune pathways remains unknown. To address this issue, the role of host miR-12 in shrimp (Marsupenaeus japonicus) antiviral immune responses was characterized in the present study. The results indicated that miR-12 participated in virus infection, host phagocytosis, and apoptosis in defense against white spot syndrome virus invasion. miR-12 could simultaneously trigger phagocytosis, apoptosis, and antiviral immunity through the synchronous downregulation of the expression of shrimp genes [PTEN (phosphatase and tensin homolog) and BI-1(transmembrane BAX inhibitor motif containing 6)] and the viral gene (wsv024). Further analysis showed that miR-12 could synchronously mediate the 5′–3′ exonucleolytic degradation of its target mRNAs, and this degradation terminated in the vicinity of the 3′ untranslated region sequence complementary to the seed sequence of miR-12. Therefore, the present study showed novel aspects of the miRNA-mediated simultaneous regulation of multiple immune pathways. PMID:28824612

Effect of long-term fertilization on humic redox mediators in multiple microbial redox reactions.

PubMed

Guo, Peng; Zhang, Chunfang; Wang, Yi; Yu, Xinwei; Zhang, Zhichao; Zhang, Dongdong

2018-03-01

This study investigated the effects of different long-term fertilizations on humic substances (HSs), humic acids (HAs) and humins, functioning as redox mediators for various microbial redox biotransformations, including 2,2',4,4',5,5'- hexachlorobiphenyl (PCB 153 ) dechlorination, dissimilatory iron reduction, and nitrate reduction, and their electron-mediating natures. The redox activity of HSs for various microbial redox metabolisms was substantially enhanced by long-term application of organic fertilizer (pig manure). As a redox mediator, only humin extracted from soils with organic fertilizer amendment (OF-HM) maintained microbial PCB 153 dechlorination activity (1.03 μM PCB 153 removal), and corresponding HA (OF-HA) most effectively enhanced iron reduction and nitrate reduction by Shewanella putrefaciens. Electrochemical analysis confirmed the enhancement of their electron transfer capacity and redox properties. Fourier transform infrared analysis showed that C=C and C=O bonds, and carboxylic or phenolic groups in HSs might be the redox functional groups affected by fertilization. This research enhances our understanding of the influence of anthropogenic fertility on the biogeochemical cycling of elements and in situ remediation ability in agroecosystems through microorganisms' metabolisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Examining the Relationship Between Pain Catastrophizing and Suicide Risk in Patients with Rheumatic Disease: the Mediating Role of Depression, Perceived Social Support, and Perceived Burdensomeness.

PubMed

Shim, Eun -Jung; Song, Yeong Wook; Park, Seung-Hee; Lee, Kwang-Min; Go, Dong Jin; Hahm, Bong-Jin

2017-08-01

Little research has examined the role of pain catastrophizing (PC) in predicting suicide among patients with rheumatic disease or the mechanisms through which it works. This study examines whether depression, perceived social support (PSS), and perceived burdensomeness (PB) mediate the relationship between PC and suicide risk. It also examines the relative importance of sociodemographic, clinical, and psychological factors in predicting suicide risk. Three hundred sixty patients from a rheumatology clinic in Korea completed measures of pain catastrophizing, social support, depression, and perceived burdensomeness. In hierarchical multiple regression analysis, the PC magnification, PB, physical disability, and PSS were significantly related to suicide risk. Results of the serial multiple mediation analysis indicated that the total indirect effect of PC magnification on suicide risk was significant while the direct effect was not. Four specific indirect effects of PC magnification were found to be statistically significant. First of all, PC magnification was associated with suicide risk through PB and through depression and PB. PC magnification was also associated with suicide risk through depression and PSS. Lastly, PC magnification was associated with suicide risk through depression, PSS, and PB. The identified pathways through which PC affects suicide risk suggest the importance of depression, PSS, and PB. Evaluation and intervention targeted at physical disability and the psychological factors of PC magnification, depression, PSS, and PB may be integrated into the management of suicide risk in patients with rheumatic disease.

An Empirical Study Analyzing Job Productivity in Toxic Workplace Environments

PubMed Central

Anjum, Amna; Ming, Xu; Siddiqi, Ahmed Faisal

2018-01-01

Purpose: This empirical study aims to determine the effects of a toxic workplace environment, which can negatively impact the job productivity of an employee. Methodology: Three hundred questionnaires were randomly distributed among the staff members of seven private universities in Pakistan with a final response rate of 89%. For analysis purposes, AMOS 22 was used to study the direct and indirect effects of the toxic workplace environment on job productivity. Confirmatory Factor Analysis (CFA) was conducted to ensure the convergent and discriminant validity of the factors, while the Hayes mediation approach was used to verify the mediating role of job burnout between the four dimensions of toxic workplace environment and job productivity. A toxic workplace with multiple dimensions, such as workplace ostracism, workplace incivility, workplace harassment, and workplace bullying, was used in this study. Findings: By using the multiple statistical tools and techniques, it has been proven that ostracism, incivility, harassment, and bullying have direct negative significant effects on job productivity, while job burnout was shown to be a statistical significant mediator between the dimensions of a toxic workplace environment and job productivity. Finally, we concluded that organizations need to eradicate the factors of toxic workplace environments to ensure their prosperity and success. Practical Implications: This study encourages managers, leaders, and top management to adopt appropriate policies for enhancing employees’ productivity. Limitations: This study was conducted by using a cross-sectional research design. Future research aims to expand the study by using a longitudinal research design. PMID:29883424

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis.

PubMed

Stillman, Chelsea M; Cohen, Jamie; Lehman, Morgan E; Erickson, Kirk I

2016-01-01

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

An Empirical Study Analyzing Job Productivity in Toxic Workplace Environments.

PubMed

Anjum, Amna; Ming, Xu; Siddiqi, Ahmed Faisal; Rasool, Samma Faiz

2018-05-21

Purpose: This empirical study aims to determine the effects of a toxic workplace environment, which can negatively impact the job productivity of an employee. Methodology: Three hundred questionnaires were randomly distributed among the staff members of seven private universities in Pakistan with a final response rate of 89%. For analysis purposes, AMOS 22 was used to study the direct and indirect effects of the toxic workplace environment on job productivity. Confirmatory Factor Analysis (CFA) was conducted to ensure the convergent and discriminant validity of the factors, while the Hayes mediation approach was used to verify the mediating role of job burnout between the four dimensions of toxic workplace environment and job productivity. A toxic workplace with multiple dimensions, such as workplace ostracism, workplace incivility, workplace harassment, and workplace bullying, was used in this study. Findings: By using the multiple statistical tools and techniques, it has been proven that ostracism, incivility, harassment, and bullying have direct negative significant effects on job productivity, while job burnout was shown to be a statistical significant mediator between the dimensions of a toxic workplace environment and job productivity. Finally, we concluded that organizations need to eradicate the factors of toxic workplace environments to ensure their prosperity and success. Practical Implications: This study encourages managers, leaders, and top management to adopt appropriate policies for enhancing employees’ productivity. Limitations: This study was conducted by using a cross-sectional research design. Future research aims to expand the study by using a longitudinal research design.

Representations as Mediation between Purposes as Junior Secondary Science Students Learn about the Human Body

ERIC Educational Resources Information Center

Olander, Clas; Wickman, Per-Olof; Tytler, Russell; Ingerman, Åke

2018-01-01

The aim of this article is to investigate students' meaning-making processes of multiple representations during a teaching sequence about the human body in lower secondary school. Two main influences are brought together to accomplish the analysis: on the one hand, theories on signs and representations as scaffoldings for learning and, on the…

Vascular risk factor burden, atherosclerosis, and functional dependence in old age: a population-based study.

PubMed

Welmer, Anna-Karin; Liang, Yajun; Angleman, Sara; Santoni, Giola; Yan, Zhongrui; Cai, Chuanzhu; Qiu, Chengxuan

2014-08-01

Vascular risk factors such as hypertension and obesity have been associated with physical limitations among older adults. The purpose of this study is to examine whether individual and aggregated vascular risk factors (VRFs) are associated with functional dependence and to what extent carotid atherosclerosis (CAS) or peripheral artery disease (PAD) may mediate the possible associations of aggregated VRFs with functional dependence. This cross-sectional study included 1,451 community-living participants aged ≥60 years in the Confucius Hometown Aging Project of China. Data on demographic features, hypertension, high total cholesterol, obesity, smoking, physical inactivity, diabetes, CAS, PAD, and cardiovascular diseases (CVDs) were collected through an interview, a clinical examination, and laboratory tests. Functional dependence was defined as being dependent in at least one activity in the personal or instrumental activities of daily living. Data were analyzed using multiple logistic models controlling for potential confounders. We used the mediation model to explore the potential mediating effect of CAS and PAD on the associations of aggregated VRFs with functional dependence. Of the 1,451 participants, 222 (15.3%) had functional dependence. The likelihood of functional dependence increased linearly with increasing number of VRFs (hypertension, high total cholesterol, abdominal obesity, and physical inactivity) (p for trend <0.002). Mediation analysis showed that controlling for demographics and CVDs up to 11% of the total association of functional dependence with clustering VRFs was mediated by CAS and PAD. Aggregation of multiple VRFs is associated with an increased likelihood of functional dependence among Chinese older adults; the association is partially mediated by carotid and peripheral artery atherosclerosis independently of CVDs.

DOES ALCOHOLICS ANONYMOUS WORK DIFFERENTLY FOR MEN AND WOMEN? A MODERATED MULTIPLE-MEDIATION ANALYSIS IN A LARGE CLINICAL SAMPLE

PubMed Central

Kelly, John F.; Hoeppner, Bettina B.

2012-01-01

Background Alcoholics Anonymous (AA) began as a male organization, but about one third is now female. Studies have found that women participate at least as much as men and benefit equally from AA, but it is unclear whether women benefit from AA in the same or different ways as men. This study tested whether gender moderated the mechanisms through which AA aids recovery. Methods A cohort study of alcohol dependent adults (N=1,726; 24% female; Project MATCH) was assessed on AA attendance during treatment; with mediators at 9 months; outcomes (Percent Days Abstinent [PDA] and Drinks per Drinking Day [DDD]) at 15 months. Multiple mediator models tested whether purported mechanisms (i.e., self-efficacy, depression, social networks, spirituality/religiosity) explained AA's effects differently for men and women controlling for baseline values, mediators, treatment, and other confounders. Results For PDA, the proportion of AA's effect accounted for by the mediators was similar for men (53%) and women (49%). Both men and women were found to benefit from changes in social factors but these mechanisms were more important among men. For DDD, the mediators accounted for 70% of the effect of AA for men and 41% for women. Again, men benefitted mostly from social changes. Independent of AA's effects, negative affect self-efficacy was shown to have a strong relationship to outcome for women but not men. Conclusions The recovery benefits derived from AA differ in nature and magnitude between men and women and may reflect differing needs based on recovery challenges related to gender-based social roles and drinking contexts. PMID:23206376

Life stressors as mediators of the relation between socioeconomic position and mental health problems in early adolescence: the TRAILS study.

PubMed

Amone-P'Olak, Kennedy; Ormel, Johan; Huisman, Martijn; Verhulst, Frank C; Oldehinkel, Albertine J; Burger, Huibert

2009-10-01

Life stressors and family socioeconomic position have often been associated with mental health status. The aim of the present study is to contribute to the understanding of the pathways from low socioeconomic position and life stressors to mental problems. In a cross-sectional analysis using data from a longitudinal study of early adolescents (N = 2,149, 51% girls; mean age 13.6 years, SD 0.53, range 12-15), we assessed the extent of mediation of the association between family socioeconomic position and mental health problems by different types of life stressors in multiple regression models. Stressors were rated as environment related or person related. Information on socioeconomic position was obtained directly from parents, and internalizing and externalizing problem behaviors were assessed by reports from multiple informants (parents, self, and teachers). Low socioeconomic position was associated with more mental health problems and more life stressors. Both environment-related and person-related stressors predicted mental health problems independently of socioeconomic position. The associations between socioeconomic position and all mental health outcomes were partly mediated by environment-related life stressors. Mediation by environment-related and person-related stressors as assessed by linear regression amounted to 56% (95% confidence interval [CI] 35%-78%) and 7% (95% CI -25% to 38%) for internalizing problems and 13% (95% CI 7%-19%) and 5% (95% CI -2% to 13%) for externalizing problems, respectively. Environment-related, but not person-related, stressors partly mediated the association between socio economic position and adolescent mental problems. The extent of mediation was larger for internalizing than for externalizing problems. Because the effect sizes of the associations were relatively small, targeted interventions to prevent impaired mental health may have only modest benefits to adolescents from low socioeconomic background.

Does Alcoholics Anonymous work differently for men and women? A moderated multiple-mediation analysis in a large clinical sample.

PubMed

Kelly, John F; Hoeppner, Bettina B

2013-06-01

Alcoholics Anonymous (AA) began as a male organization, but about one third is now female. Studies have found that women participate at least as much as men and benefit equally from AA, but it is unclear whether women benefit from AA in the same or different ways as men. This study tested whether gender moderated the mechanisms through which AA aids recovery. A cohort study of alcohol dependent adults (N=1726; 24% female; Project MATCH) was assessed on AA attendance during treatment; with mediators at 9 months; outcomes (Percent Days Abstinent [PDA] and Drinks per Drinking Day [DDD]) at 15 months. Multiple mediator models tested whether purported mechanisms (i.e., self-efficacy, depression, social networks, spirituality/religiosity) explained AA's effects differently for men and women controlling for baseline values, mediators, treatment, and other confounders. For PDA, the proportion of AA's effect accounted for by the mediators was similar for men (53%) and women (49%). Both men and women were found to benefit from changes in social factors but these mechanisms were more important among men. For DDD, the mediators accounted for 70% of the effect of AA for men and 41% for women. Again, men benefitted mostly from social changes. Independent of AA's effects, negative affect self-efficacy was shown to have a strong relationship to outcome for women but not men. The recovery benefits derived from AA differ in nature and magnitude between men and women and may reflect differing needs based on recovery challenges related to gender-based social roles and drinking contexts. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Do young people benefit from AA as much, and in the same ways, as adult aged 30+? A moderated multiple mediation analysis.

PubMed

Hoeppner, Bettina B; Hoeppner, Susanne S; Kelly, John F

2014-10-01

Research has shown that participation in Alcoholics Anonymous (AA) confers significant recovery benefit to adults suffering from alcohol use disorder (AUD). Concerns persist, however, that AA may not work as well for younger adults, who tend to have shorter addiction histories, different social circumstances, and less spiritual/religious interest than adults. Secondary data analysis of Project MATCH, using a prospective, moderated multiple mediation analysis to test and compare six previously identified mechanisms of change in younger adults (n=266) vs. adults aged 30+ (n=1460). Nine clinical sites within the United States. Treatment-seeking adults (n=1726) suffering from AUD who participated in 12 weeks of outpatient treatment and completed follow-ups at 3-, 9- and 15-months. AA attendance during treatment; mediators at 9 months; and outcomes [percentage of days abstinent (PDA) and drinks per drinking day (DDD)] at 15 months. AA attendance was associated with improved drinking outcomes in both younger adults (PDA: F(1, 247)=8.55, p<0.01; DDD: F(1, 247)=15.93, p<0.01) and adults aged 30+ (PDA: F(1, 1311)=86.58, p<0.01; DDD: F(1, 1311)=11.96, p<0.01). Only two of the six hypothesized pathways (i.e., decreases in pro-drinking social networks, self-efficacy in social situations) appeared to work in younger adults. Unidentified mechanisms of behavior change that are mobilized by AA participation appear to be at work in young people. Once identified, these mechanisms may shed new light on how exactly AA confers similar benefits for young people and, more broadly, may enhance our understanding of recovery-related change for young adults that could yield novel intervention targets. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation.

PubMed

Malik, Sohail; Roeder, Robert G

2010-11-01

The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action of numerous other co-activators and co-repressors, including those acting at the level of chromatin. These interactions ultimately allow the Mediator to deliver outputs that range from maximal activation of genes to modulation of basal transcription to long-term epigenetic silencing.

How do Housing Subsidies Improve Quality of Life Among Homeless Adults? A Mediation Analysis.

PubMed

O'Connell, Maria; Sint, Kyaw; Rosenheck, Robert

2018-03-01

Supported housing, combining rent subsidies with intensive case management, is associated with improvements in quality of life of homeless adults, but factors mediating their impact on quality of life have not been studied. Twelve-month outcome data from a randomized trial of the Housing and Urban Development- Veterans Affairs Supported Housing program (HUD-VASH) showed that access to a housing rent subsidy plus intensive case management (ICM) was associated with greater improvement in subjective quality of life than ICM alone. Multiple mediation analyses were applied to identify variables that significantly mediated the relationship between receipt of housing voucher and improvements in quality of life. Significant mediating covariates were those whose 95% bias-corrected confidence intervals, when added to the model predicting improvement in quality of life, did not overlap zero. Increases in the number of days housed, size of social network, and availability of emotional support appear to mediate improvement in quality of life and account for 71% of the benefit attributable to having a rent subsidy. Improvement in subjective quality of life though housing subsidies is mediated by gains in both material and psychosocial factors. Mediating factors deserve special attention in supported housing services. © Society for Community Research and Action 2018.

Wuling powder prevents the depression-like behavior in learned helplessness mice model through improving the TSPO mediated-mitophagy.

PubMed

Li, Dongmei; Zheng, Ji; Wang, Mingyang; Feng, Lu; Liu, Yanyong; Yang, Nan; Zuo, Pingping

2016-06-20

Wuling powder (trade name: Wuling capsule), a traditional Chinese medicine (TCM), was extracted from mycelia of precious Xylaria Nigripes (Kl.) Sacc by modern fermentation technology, and has been claimed to be fully potent in improving the signs of insomnia and cognitive deficits. Moreover, Wuling capsule was effective in treating post-stroke and orther co-cormbid depression both in clinical and in basic research. In order to clarify the molecular mechanisms of the antidepressant effect of Wuling powder, we established learned helplessness (LH) depression animal model and focused on 18kDa translocator protein (TSPO) mediated-mitophagy pathway. Mice were exposed to the inescapable e-shock (IS) once a day for three consecutive days to establish the LH model. Then mice were orally administered Wuling powder for 2 weeks. For the behavioral assessment, Shuttle box test, novelty suppressed feeding test (NSF) and forced swimming test (FST) were performed. Following the behavioral assessment, we assessed the protein expression level that were related to TSPO-mediated mitophagy signaling pathway by Western blotting analysis. Finally, immunohistochemistry method was used to assess the neuroprotective effects of Wuling powder. Compared with mice that were subjected to inescapable e-shock, Wuling powder exhibited antidepressant effect in the multiple behavioral tests. In addition, Wuling powder altered the expression level of multiple proteins related to TSPO-mediated mitophagy signaling pathway. Our results suggested that Wuling powder exhibited an obvious antidepressant effect, which could be due to the improvement of TSPO-mediated mitophagy signaling pathway. Copyright © 2016. Published by Elsevier Ireland Ltd.

Multiple transport systems mediate virus-induced acquired resistance to oxidative stress

USDA-ARS?s Scientific Manuscript database

In this paper, we report the phenomenon of acquired cross-tolerance to oxidative (UV-C and H2O2) stress in Nicotiana benthamiana plants infected with Potato virus X (PVX) and investigate the functional expression of transport systems in mediating this phenomenon. By combining multiple approaches, we...

Epigenomics of Hypertension

PubMed Central

Liang, Mingyu; Cowley, Allen W.; Mattson, David L.; Kotchen, Theodore A.; Liu, Yong

2013-01-01

Multiple genes and pathways are involved in the pathogenesis of hypertension. Epigenomic studies of hypertension are beginning to emerge and hold great promise of providing novel insights into the mechanisms underlying hypertension. Epigenetic marks or mediators including DNA methylation, histone modifications, and non-coding RNA can be studied at a genome or near-genome scale using epigenomic approaches. At the single gene level, several studies have identified changes in epigenetic modifications in genes expressed in the kidney that correlate with the development of hypertension. Systematic analysis and integration of epigenetic marks at the genome scale, demonstration of cellular and physiological roles of specific epigenetic modifications, and investigation of inheritance are among the major challenges and opportunities for future epigenomic and epigenetic studies of hypertension. Essential hypertension is a multifactorial disease involving multiple genetic and environmental factors and mediated by alterations in multiple biological pathways. Because the non-genetic mechanisms may involve epigenetic modifications, epigenomics is one of the latest concepts and approaches brought to bear on hypertension research. In this article, we summarize briefly the concepts and techniques for epigenomics, discuss the rationale for applying epigenomic approaches to study hypertension, and review the current state of this research area. PMID:24011581

cit: hypothesis testing software for mediation analysis in genomic applications.

PubMed

Millstein, Joshua; Chen, Gary K; Breton, Carrie V

2016-08-01

The challenges of successfully applying causal inference methods include: (i) satisfying underlying assumptions, (ii) limitations in data/models accommodated by the software and (iii) low power of common multiple testing approaches. The causal inference test (CIT) is based on hypothesis testing rather than estimation, allowing the testable assumptions to be evaluated in the determination of statistical significance. A user-friendly software package provides P-values and optionally permutation-based FDR estimates (q-values) for potential mediators. It can handle single and multiple binary and continuous instrumental variables, binary or continuous outcome variables and adjustment covariates. Also, the permutation-based FDR option provides a non-parametric implementation. Simulation studies demonstrate the validity of the cit package and show a substantial advantage of permutation-based FDR over other common multiple testing strategies. The cit open-source R package is freely available from the CRAN website (https://cran.r-project.org/web/packages/cit/index.html) with embedded C ++ code that utilizes the GNU Scientific Library, also freely available (http://www.gnu.org/software/gsl/). joshua.millstein@usc.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Thidiazuron-enhanced biosynthesis and antimicrobial efficacy of silver nanoparticles via improving phytochemical reducing potential in callus culture of Linum usitatissimum L.

PubMed Central

Anjum, Sumaira; Abbasi, Bilal Haider

2016-01-01

Green synthesis of silver nanoparticles (AgNPs) by using plants is an emerging class of nanobiotechnology. It revolutionizes all domains of medical sciences by synthesizing chemical-free AgNPs for various biomedical applications. In this report, AgNPs were successfully synthesized by using whole plant extract (WPE) and thidiazuron-induced callus extract (CE) of Linum usitatissimum. The phytochemical analysis revealed that the total phenolic and flavonoid contents were higher in CE than that in WPE. Ultraviolet-visible spectroscopy of synthesized AgNPs showed a characteristic surface plasmon band in the range of 410–426 nm. Bioreduction of CE-mediated AgNPs was completed in a shorter time than that of WPE-mediated AgNPs. Scanning electron microscopy showed that both types of synthesized AgNPs were spherical in shape, but CE-mediated AgNPs were smaller in size (19–24 nm) and more scattered in distribution than that of WPE-mediated AgNPs (49–54 nm). X-ray diffraction analysis confirmed crystalline nature (face-centered cubic) of both types of AgNPs. Fourier-transform infrared spectroscopy revealed that the polyphenols and flavonoids were mainly responsible for reduction and capping of synthesized AgNPs. Energy dispersive X-ray analysis further confirmed the successful synthesis of AgNPs. Moreover, the synthesized AgNPs were found to be stable over months with no change in the surface plasmon bands. More importantly, CE-mediated AgNPs displayed significantly higher bactericidal activity against multiple drug-resistant human pathogens than WPE-mediated AgNPs. The present work highlighted the potent role of thidiazuron in in vitro-derived cultures for enhanced biosynthesis of chemical-free AgNPs, which can be used as nanomedicines in many biomedical applications. PMID:26955271

Transcriptome-Wide Analysis of Hepatitis B Virus-Mediated Changes to Normal Hepatocyte Gene Expression.

PubMed

Lamontagne, Jason; Mell, Joshua C; Bouchard, Michael J

2016-02-01

Globally, a chronic hepatitis B virus (HBV) infection remains the leading cause of primary liver cancer. The mechanisms leading to the development of HBV-associated liver cancer remain incompletely understood. In part, this is because studies have been limited by the lack of effective model systems that are both readily available and mimic the cellular environment of a normal hepatocyte. Additionally, many studies have focused on single, specific factors or pathways that may be affected by HBV, without addressing cell physiology as a whole. Here, we apply RNA-seq technology to investigate transcriptome-wide, HBV-mediated changes in gene expression to identify single factors and pathways as well as networks of genes and pathways that are affected in the context of HBV replication. Importantly, these studies were conducted in an ex vivo model of cultured primary hepatocytes, allowing for the transcriptomic characterization of this model system and an investigation of early HBV-mediated effects in a biologically relevant context. We analyzed differential gene expression within the context of time-mediated gene-expression changes and show that in the context of HBV replication a number of genes and cellular pathways are altered, including those associated with metabolism, cell cycle regulation, and lipid biosynthesis. Multiple analysis pipelines, as well as qRT-PCR and an independent, replicate RNA-seq analysis, were used to identify and confirm differentially expressed genes. HBV-mediated alterations to the transcriptome that we identified likely represent early changes to hepatocytes following an HBV infection, suggesting potential targets for early therapeutic intervention. Overall, these studies have produced a valuable resource that can be used to expand our understanding of the complex network of host-virus interactions and the impact of HBV-mediated changes to normal hepatocyte physiology on viral replication.

Thidiazuron-enhanced biosynthesis and antimicrobial efficacy of silver nanoparticles via improving phytochemical reducing potential in callus culture of Linum usitatissimum L.

PubMed

Anjum, Sumaira; Abbasi, Bilal Haider

2016-01-01

Green synthesis of silver nanoparticles (AgNPs) by using plants is an emerging class of nanobiotechnology. It revolutionizes all domains of medical sciences by synthesizing chemical-free AgNPs for various biomedical applications. In this report, AgNPs were successfully synthesized by using whole plant extract (WPE) and thidiazuron-induced callus extract (CE) of Linum usitatissimum. The phytochemical analysis revealed that the total phenolic and flavonoid contents were higher in CE than that in WPE. Ultraviolet-visible spectroscopy of synthesized AgNPs showed a characteristic surface plasmon band in the range of 410-426 nm. Bioreduction of CE-mediated AgNPs was completed in a shorter time than that of WPE-mediated AgNPs. Scanning electron microscopy showed that both types of synthesized AgNPs were spherical in shape, but CE-mediated AgNPs were smaller in size (19-24 nm) and more scattered in distribution than that of WPE-mediated AgNPs (49-54 nm). X-ray diffraction analysis confirmed crystalline nature (face-centered cubic) of both types of AgNPs. Fourier-transform infrared spectroscopy revealed that the polyphenols and flavonoids were mainly responsible for reduction and capping of synthesized AgNPs. Energy dispersive X-ray analysis further confirmed the successful synthesis of AgNPs. Moreover, the synthesized AgNPs were found to be stable over months with no change in the surface plasmon bands. More importantly, CE-mediated AgNPs displayed significantly higher bactericidal activity against multiple drug-resistant human pathogens than WPE-mediated AgNPs. The present work highlighted the potent role of thidiazuron in in vitro-derived cultures for enhanced biosynthesis of chemical-free AgNPs, which can be used as nanomedicines in many biomedical applications.

Relationships between stress, negative emotions, resilience, and smoking: Testing a moderated mediation model

PubMed Central

Wang, Yan; Chen, Xinguang; Gong, Jie; Yan, Yaqiong

2016-01-01

Objective More effective tobacco prevention and cessation programs require in-depth understanding of the mechanism by which multiple factors interact with each other to affect smoking behaviors. Stress has long been recognized as a risk factor for smoking. However, the underlying mediation and moderation mechanisms are far from clear. The purpose of this study was to examine the role of negative emotions in mediating the link between stress and smoking and whether this indirect link was modified by resilience. Methods Survey data were collected using audio computer assisted self-interview (ACASI) from a large random sample of urban residents (n=1249, mean age = 35.1, 45.3% male) in Wuhan, China. Perceived stress, negative emotions (anxiety, depression), resilience were measured with reliable instruments also validated in China. Self-reported smoking was validated with exhaled carbon monoxide. Results Mediation analysis indicated that two negative emotions fully mediated the link between stress and intensity of smoking (assessed by number of cigarettes smoked per day, effect = .082 for anxiety and .083 for depression) and nicotine dependence (assessed by DSM-IV standard, effect = .134 for anxiety and .207 for depression). Moderated mediation analysis demonstrated that the mediation effects of negative emotions were negatively associated with resilience. Conclusions Results suggest resilience interacts with stress and negative emotions to affect the risk of tobacco use and nicotine dependence among Chinese adults. Further research with longitudinal data is needed to verify the findings of this study and to estimate the effect size of resilience in tobacco intervention and cessation programs. PMID:26894428

Experienced stigma and its impacts in psychosis: The role of social rank and external shame.

PubMed

Wood, Lisa; Irons, Chris

2017-09-01

Experienced stigma is detrimental to those who experience psychosis and can cause emotional distress and hinder recovery. This study aimed to explore the relationship between experienced stigma with emotional distress and recovery in people with psychosis. It explored the role of external shame and social rank as mediators in these relationships. A cross-sectional design was implemented. Fifty-two service users were administered a battery of questionnaires examining experienced stigma, external shame, social rank, personal recovery, positive symptoms, depression, and anxiety. Correlation and multiple regression analysis were conducted on the data. Where appropriate, mediation analysis was employed to explore social rank and external shame as mediatory variables. Experienced stigma was significantly related to shame (social rank and external shame), positive symptoms, emotional distress (depression and anxiety), and personal recovery. The impact of experienced stigma on depression was mediated by external shame. Social rank was a mediator between experienced stigma and personal recovery only. People with psychosis who have experienced stigma are likely to experience emotional distress and be inhibited in their recovery. This was found to be partly mediated by external shame and low social rank. Clinical approaches to stigma need to target these as potential maintenance factors. Experienced stigma is significantly related to shame (social rank and external shame) emotional distress, and reduced personal recovery. External shame mediated the relationship between experienced stigma and depression in psychosis. Social rank mediated the relationship between experienced stigma and personal recovery. Clinical approaches to stigma should include the assessment of external shame and low social rank. © 2017 The British Psychological Society.

Adult attachment, hostile conflict, and relationship adjustment among couples facing multiple sclerosis.

PubMed

Crangle, Cassandra J; Hart, Tae L

2017-11-01

Couples facing multiple sclerosis (MS) report significantly elevated rates of relationship distress, yet the effects of attachment have never been examined in this population. We examined whether hostile conflict mediated the dyadic effects of attachment on relationship adjustment in couples facing MS and whether these associations were moderated by gender or role. We also explored whether dyadic adjustment mediated the relationship between attachment and hostile conflict. The study was cross-sectional and included 103 couples in which one partner had been diagnosed with MS. Participants completed the Experiences in Close Relationships-Revised, Dyadic Adjustment Scale, and Aversive Interactions Scale, as well as demographic variables. We used the actor-partner interdependence model for data analysis. There were significant actor and partner effects of greater anxious attachment and worse dyadic adjustment. Actor and partner effects of anxious attachment were significantly mediated by greater hostile conflict. Gender significantly moderated the effects between avoidant attachment and dyadic adjustment. The actor effect was significant for males and females; the partner effect was only significant for females. The actor effect for females but not males was significantly mediated by greater hostile conflict. Role was not a significant moderator. Exploratory analyses also showed that dyadic adjustment mediated the relationship between anxious and avoidant attachment and hostile conflict. Findings highlight the important effects of attachment on relationship adjustment in MS couples. Both hostile conflict and dyadic adjustment appear to be mechanisms through which insecure attachment has a detrimental effect. Statement of contribution What is already known on this subject? Despite higher-than-normal rates of marital distress and separation/divorce, the effects of attachment on relationship adjustment among couples facing multiple sclerosis have never been examined. Prior studies within healthy populations have supported within-person and cross-dyadic associations between attachment and relationship adjustment; however, they have failed to use dyadic analyses. Hostile conflict has been associated with both insecure attachment and relationship adjustment and therefore may be an important mediator to help understand these relationships. What does this study add? Women were more negatively affected by their partner's avoidant attachment then men. Hostile conflict mediated the effects of anxious attachment on dyadic adjustment for individuals and across dyads. Hostile conflict accounted for the individual effect of avoidant attachment on dyadic adjustment for women. © 2017 The British Psychological Society.

Contribution of Theory of Mind, Executive Functioning, and Pragmatics to Socialization Behaviors of Children with High-Functioning Autism.

PubMed

Berenguer, Carmen; Miranda, Ana; Colomer, Carla; Baixauli, Inmaculada; Roselló, Belén

2018-02-01

Social difficulties are a key aspect of autism, but the intervening factors are still poorly understood. This study had two objectives: to compare the profile of ToM skills, executive functioning (EF), and pragmatic competence (PC) of children with high-functioning autism (HFA) and children with typical development (TD), and analyze their mediator role in social functioning. The participants were 52 children with HFA and 37 children with TD matched on age, intelligence quotient, and expressive vocabulary. Significant differences were found on measures of ToM, both explicit and applied, EF, and PC between children with HFA and TD. Multiple mediation analysis revealed that applied ToM skills and PC mediated the relations between autism symptoms and social functioning. Implications for social cognitive interventions to address these findings are discussed.

CRISPR/Cas9 mediates efficient conditional mutagenesis in Drosophila.

PubMed

Xue, Zhaoyu; Wu, Menghua; Wen, Kejia; Ren, Menda; Long, Li; Zhang, Xuedi; Gao, Guanjun

2014-09-05

Existing transgenic RNA interference (RNAi) methods greatly facilitate functional genome studies via controlled silencing of targeted mRNA in Drosophila. Although the RNAi approach is extremely powerful, concerns still linger about its low efficiency. Here, we developed a CRISPR/Cas9-mediated conditional mutagenesis system by combining tissue-specific expression of Cas9 driven by the Gal4/upstream activating site system with various ubiquitously expressed guide RNA transgenes to effectively inactivate gene expression in a temporally and spatially controlled manner. Furthermore, by including multiple guide RNAs in a transgenic vector to target a single gene, we achieved a high degree of gene mutagenesis in specific tissues. The CRISPR/Cas9-mediated conditional mutagenesis system provides a simple and effective tool for gene function analysis, and complements the existing RNAi approach. Copyright © 2014 Xue et al.

An in vivo requirement for the mediator subunit med14 in the maintenance of stem cell populations.

PubMed

Burrows, Jeffrey T A; Pearson, Bret J; Scott, Ian C

2015-04-14

The Mediator complex has recently been shown to be a key player in the maintenance of embryonic and induced pluripotent stem cells. However, the in vivo consequences of loss of many Mediator subunits are unknown. We identified med14 as the gene affected in the zebrafish logelei (log) mutant, which displayed a morphological arrest by 2 days of development. Surprisingly, microarray analysis showed that transcription was not broadly affected in log mutants. Indeed, log cells transplanted into a wild-type environment were able to survive into adulthood. In planarians, RNAi knockdown demonstrated a requirement for med14 and many other Mediator components in adult stem cell maintenance and regeneration. Multiple stem/progenitor cell populations were observed to be reduced or absent in zebrafish med14 mutant embryos. Taken together, our results show a critical, evolutionarily conserved, in vivo function for Med14 (and Mediator) in stem cell maintenance, distinct from a general role in transcription. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Insulin-like growth factor-1 is a mediator of age-related decline of bone health status in men.

PubMed

Chin, Kok-Yong; Ima-Nirwana, Soelaiman; Mohamed, Isa Naina; Hanapi Johari, Mohamad; Ahmad, Fairus; Mohamed Ramli, Elvy Suhana; Wan Ngah, Wan Zurinah

2014-06-01

The role of insulin-like growth factor-1 (IGF-1) in bone health in men is debatable. This study aimed to determine whether IGF-1 is a mediator in age-related decline of bone health status measured by calcaneal speed of sound (SOS) in Malaysian men. The study recruited 279 Chinese and Malay men. Their demographic data, weight, height, calcaneal SOS were taken and fasting blood was collected for total testosterone, sex-hormone binding globulin and IGF-1 assays. The associations between the studied variables were assessed using multiple linear regression (MLR) analysis. Mediator analysis was performed using Sobel test. There was a significant and parallel decrease of IGF-1 and SOS with age (p < 0.05). Serum IGF-1 was significantly and positively associated with SOS (p < 0.05) but after further adjustment for age, the significance was lost (p > 0.05). The strength of the association between age and SOS decreased after adjusting for IGF-1 level but it remained significant (p < 0.05). Sobel test revealed that IGF-1 was a significant partial mediator in the relationship between age and SOS (z = -4.3). Serum IGF-1 is a partial mediator in the age-related decline of bone health in men as determined by calcaneal ultrasound. A prospective study should be performed to validate this relationship.

Toward a Theory of Web-Mediated Knowledge Synthesis: How Advanced Learners Used the Web to Construct Knowledge about Climate Change Behavior

ERIC Educational Resources Information Center

DeSchryver, Michael

2012-01-01

This dissertation utilized a multiple case study design to explore how advanced learners synthesize information about ill-structured topics when reading-to-learn and reading-to-do on the Web. Eight graduate students provided data in the form of think-alouds, interviews, screen video, digital trails, and task artifacts. Data analysis was based on…

Maternal Anxiety and Separation Anxiety in Children Aged Between 3 and 6 Years: The Mediating Role of Parenting Style.

PubMed

Orgilés, Mireia; Penosa, Patricia; Morales, Alexandra; Fernández-Martínez, Iván; Espada, José P

2018-06-04

Maternal anxiety is known to be associated with childhood separation anxiety. However, there is little research on the mediating factors of this relationship, despite the possible consequences separation anxiety might have for children's development and autonomy. The objective of this study was to analyze the possible mediating effects of 4 parenting styles (overprotective, assertive, punitive, and inhibited) on the relationship between maternal anxiety and child separation anxiety. Participants were 235 mothers with children aged 3 to 6 years, recruited from 6 preschools in the southeast of Spain. Maternal trait anxiety, maternal parenting style, and child separation anxiety were evaluated. A parallel multiple-mediation analysis revealed that the overprotective parenting style was a significant mediator of the relationship between maternal trait anxiety and child separation anxiety. In addition, mothers with higher trait anxiety scores exhibited a greater likelihood of using an overprotective, punitive, or less assertive parenting style. Younger mothers were more likely to use an overprotective parenting style, and compared with girls, boys were more exposed to the assertive style. This study provides initial evidence that parenting style acts as a mediator of the relationship between maternal anxiety and child separation anxiety.

The mediational role of helplessness in psychological outcomes in systemic lupus erythematosus.

PubMed

Mills, S D; Azizoddin, D; Gholizadeh, S; Racaza, G Z; Nicassio, P M

2018-06-01

Objective Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can result in disability and psychological distress. Although pain has been associated with depressive symptomatology and stress in SLE, a paucity of theoretical models have been used to explain the relationship between pain and psychological distress in this population. Thus, the present study examined helplessness as a mediator of the relationship between pain and psychological distress among patients with SLE. Methods Multiple mediation analysis was used to examine the hypothesis that learned helplessness mediates the relationship between pain and symptoms of anxiety, depression, and stress in a sample of patients with SLE ( N = 136) receiving medical care at Cedars Sinai Medical Center. Results The mean score on the Helplessness subscale was 14.5 ( SD = 5.4). Helplessness fully mediated the relationship between pain vitality and symptoms of anxiety (BCa 95% CI (-0.073, -0.015)), depression (BCa 95% CI (-0.502, -0.212)), and stress (BCa 95% CI (-0.063, -0.027)). Conclusion Participants reported a high level of perceived inability to control one's disease. Helplessness fully mediated the relationship between pain and measures of anxiety, depression, and perceived stress among patients with SLE.

CAREGIVER-CHILD INTERACTION, CAREGIVER TRANSITIONS, AND GROUP SIZE AS MEDIATORS BETWEEN INTERVENTION CONDITION AND ATTACHMENT AND PHYSICAL GROWTH OUTCOMES IN INSTITUTIONALIZED CHILDREN.

PubMed

Warner, Hilary A; McCall, Robert B; Groark, Christina J; Kim, Kevin H; Muhamedrahimov, Rifkat J; Palmov, Oleg I; Nikiforova, Natalia V

2017-09-01

This report describes a secondary analysis of data from a comprehensive intervention project which included training and structural changes in three Baby Homes in St. Petersburg, Russian Federation. Multiple mediator models were tested according to the R.M. Baron and D.A. Kenny () causal-steps approach to examine whether caregiver-child interaction quality, number of caregiver transitions, and group size mediated the effects of the intervention on children's attachment behaviors and physical growth. The study utilized a subsample of 163 children from the original Russian Baby Home project, who were between 11 and 19 months at the time of assessment. Results from comparisons of the training and structural changes versus no intervention conditions are presented. Caregiver-child interaction quality and number of caregiver transitions fully mediated the association between intervention condition and attachment behavior. No other mediation was found. Results suggest that the quality of interaction between caregivers and children in institutional care is of primary importance to children's development, but relationship context may play a less direct mediational role, supporting caregiver-child interactions. © 2017 Michigan Association for Infant Mental Health.

From Animal House to Old School: a multiple mediation analysis of the association between college drinking movie exposure and freshman drinking and its consequences.

PubMed

Osberg, Timothy M; Billingsley, Katherine; Eggert, Meredith; Insana, Maribeth

2012-08-01

Does exposure to college drinking movies impact upon subsequent college student drinking? If so, what mechanisms mediate such an effect? In the first study to address these questions, we assessed college drinking movie exposure in a sample of 479 college freshmen early in their first semester and examined its relation to subsequent drinking and drinking consequences one month later. Hypothesized mediators of this effect included college alcohol beliefs (beliefs that drinking is central to college life), positive and negative alcohol expectancies, and descriptive and injunctive norms. Using bootstrapping procedures, results indicated that movie exposure exerted direct effects on both drinking and drinking consequences. Movie exposure also had significant indirect effects on drinking through all of the hypothesized mediators, with the exception of negative alcohol expectancies. All mediated movie exposure's effects on drinking consequences, with the exception of injunctive norms. Contrast analyses revealed that college alcohol beliefs had the strongest mediational effects in the relationship between movie exposure and both drinking and consequences. The implications of these findings for precollege alcohol education programs are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Utilized social support and self-esteem mediate the relationship between perceived social support and suicide ideation. A test of a multiple mediator model.

PubMed

Kleiman, Evan M; Riskind, John H

2013-01-01

While perceived social support has received considerable research as a protective factor for suicide ideation, little attention has been given to the mechanisms that mediate its effects. We integrated two theoretical models, Joiner's (2005) interpersonal theory of suicide and Leary's (Leary, Tambor, Terdal, & Downs, 1995) sociometer theory of self-esteem to investigate two hypothesized mechanisms, utilization of social support and self-esteem. Specifically, we hypothesized that individuals must utilize the social support they perceive that would result in increased self-esteem, which in turn buffers them from suicide ideation. Participants were 172 college students who completed measures of social support, self-esteem, and suicide ideation. Tests of simple mediation indicate that utilization of social support and self-esteem may each individually help to mediate the perceived social support/suicide ideation relationship. Additionally, a test of multiple mediators using bootstrapping supported the hypothesized multiple-mediator model. The use of a cross-sectional design limited our ability to find true cause-and-effect relationships. Results suggested that utilized social support and self-esteem both operate as individual moderators in the social support/self-esteem relationship. Results further suggested, in a comprehensive model, that perceived social support buffers suicide ideation through utilization of social support and increases in self-esteem.

Socioeconomic Associations with ADHD: Findings from a Mediation Analysis.

PubMed

Russell, Abigail Emma; Ford, Tamsin; Russell, Ginny

2015-01-01

Children from disadvantaged socioeconomic backgrounds are at greater risk of a range of negative outcomes throughout their life course than their peers; however the specific mechanisms by which socioeconomic status relates to different health outcomes in childhood are as yet unclear. The current study investigates the relationship between socioeconomic disadvantage in childhood and attention deficit/hyperactivity disorder (ADHD), and investigates putative mediators of this association in a longitudinal population-based birth cohort in the UK. Data from the Avon Longitudinal Study of Parents and Children was used (n = 8,132) to explore the relationship between different measures of socioeconomic status at birth-3 years and their association with a diagnosis of ADHD at age 7. A multiple mediation model was utilised to examine factors occurring between these ages that may mediate the association. Financial difficulties, housing tenure, maternal age at birth of child and marital status were significantly associated with an outcome of ADHD, such that families either living in financial difficulty, living in council housing, with younger or single mothers' were more likely to have a child with a research diagnosis of ADHD at age 7. Financial difficulties was the strongest predictor of ADHD (OR 2.23 95% CI 1.57-3.16). In the multiple mediation model, involvement in parenting at age 6 and presence of adversity at age 2-4 mediated 27.8% of the association. Socioeconomic disadvantage, conceptualised as reported difficulty in affording basic necessities (e.g. heating, food) has both direct and indirect impacts on a child's risk of ADHD. Lower levels of parent involvement mediates this association, as does presence of adversity; with children exposed to adversity and those with less involved parents being at an increased risk of having ADHD. This study highlights the importance of home and environmental factors as small but important contributors toward the aetiology of ADHD.

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2013-01-01

The increasing availability of data from multi-site randomized trials provides a potential opportunity to use instrumental variables methods to study the effects of multiple hypothesized mediators of the effect of a treatment. We derive nine assumptions needed to identify the effects of multiple mediators when using site-by-treatment interactions…

Vulnerability to depression: A moderated mediation model of the roles of child maltreatment, peer victimization, and 5-HTTLPR genetic variation among children from low-SES backgrounds

PubMed Central

Banny, Adrienne M.; Cicchetti, Dante; Rogosch, Fred A.; Oshri, Assaf; Crick, Nicki R.

2014-01-01

Child maltreatment, peer victimization, and a polymorphism of the serotonin transporter gene (5-HTTLPR) were examined as predictors of depressive symptomatology. Children (M age = 11.26, SD = 1.65), including 156 maltreated and 145 nonmaltreated children from comparable low socioeconomic backgrounds, provided DNA samples and self-reports of relational peer victimization, overt peer victimization, and depressive symptoms. Path analysis showed that relational and overt victimization mediated the association between child maltreatment and depressive symptoms. Bootstrapping procedures were used to test moderated mediation and demonstrated that genotype moderated the indirect effects of relational and overt victimization on child depressive symptoms, such that victimized children with the l/l variation were at an increased risk for depressive symptoms compared to victimized children carrying an s allele. Results highlight the utility of examining process models that incorporate biological and psychological factors contributing to the development of depressive symptomatology, and provide direction toward understanding and promoting resilience among high risk youth from a multiple levels of analysis approach. PMID:23880379

Serial multiple mediation of organizational commitment and job burnout in the relationship between psychological capital and anxiety in Chinese female nurses: A cross-sectional questionnaire survey.

PubMed

Zhou, Jiawei; Yang, Yanjie; Qiu, Xiaohui; Yang, Xiuxian; Pan, Hui; Ban, Bo; Qiao, Zhengxue; Wang, Lin; Wang, Wenbo

2018-07-01

Nurses play an important role in medical and health services but anxiety among those in this profession is widespread. Anxiety not only damages the physical and mental health of the individual, but also reduces the efficiency of their work and the quality of care, ultimately impacting on patient care. Therefore, it is necessary to elucidate the factors that lead to anxiety and explore measures to reduce the impact these factors have on nurses. The purpose of this study was to investigate the serial-multiple mediation of psychological capital (PsyCap), organizational commitment, job burnout, and anxiety among Chinese female nurses. A cross-sectional stratified cluster sampling study. The study consisted of 1354 Chinese female nurses from two tertiary grade A hospitals in Heilongjiang Province, China. The Zung Self-Rating Anxiety Scale, the Chinese psychological capital questionnaire, the Chinese Maslach Burnout Inventory, and the Chinese Employee Organizational Commitment Questionnaire were used to gather data. Descriptive analysis, independent-samples T-test, one-way analysis of variance, Spearman correlation analyses, ordinary least-squares regression and the bootstrap method were used to analyze data. The prevalence rate of anxiety among nurses was found to be 41.1%, and there were significant differences in anxiety symptoms in age (F = 15.54, p < 0.001) and marital status (F = 5.41, p < 0.001), but not education (F = 1.50, p = 0.224) among nurses. Overall, the serial-multiple mediation of organizational commitment and job burnout in the relationship between PsyCap and anxiety was found to be statistically significant. The results of the present study showed that positive PsyCap was sequentially associated with increased organizational commitment first, and then decreased job burnout, which was in turn related to reduced symptoms of anxiety among female nurses. Copyright © 2018. Published by Elsevier Ltd.

Association between injury pattern of patients with multiple injuries and circulating levels of soluble tumor necrosis factor receptors, interleukin-6 and interleukin-10, and polymorphonuclear neutrophil elastase.

PubMed

Hensler, Thorsten; Sauerland, Stefan; Bouillon, Bertil; Raum, Marcus; Rixen, Dieter; Helling, Hanns-J; Andermahr, Jonas; Neugebauer, Edmund A M

2002-05-01

Our knowledge about the bidirectional interactions between brain and whole organism after trauma is still limited. It was the purpose of this prospective clinical study to determine the influence of severe head trauma (SHT) as well as trauma in different anatomic injury regions on posttraumatic inflammatory mediator levels from patients with multiple injuries. Thirty-five healthy controls, 33 patients with an isolated SHT, 47 patients with multiple injuries without SHT, and 45 patients with both SHT and multiple injuries were studied. The posttraumatic plasma levels of soluble tumor necrosis factor receptors p55 and p75, interleukin (IL)-6, IL-10, and polymorphonuclear neutrophil (PMN) elastase were monitored using enzyme-linked immunosorbent assay technique. The influence of head injuries as well as thorax, abdomen, and extremity injuries on the mediator release from patients with multiple injuries was investigated by multivariate linear regression models. The soluble tumor necrosis factor receptor p55/p75 ratio was significantly elevated within 3 hours of trauma in all three injury groups and returned to reference ratios after 12 hours. The lowest increase was found in patients suffering from an isolated SHT. Lowest mediator levels in this patient population were also found for IL-6, IL-10, and PMN elastase during the first 36 hours after trauma. Additional injuries to the head, thorax, abdomen, and extremity modulated mediator levels to a different degree. No specific effect was found for SHT when compared with other injury groups. Thorax injuries caused the quickest rise in mediator levels, whereas abdominal injuries significantly increased PMN elastase levels 12 to 24 hours after trauma. Traumatic injuries cause the liberation of various mediators, without any specific association between anatomic injury pattern and the pattern of mediator release.

Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci.

PubMed

Canver, Matthew C; Lessard, Samuel; Pinello, Luca; Wu, Yuxuan; Ilboudo, Yann; Stern, Emily N; Needleman, Austen J; Galactéros, Frédéric; Brugnara, Carlo; Kutlar, Abdullah; McKenzie, Colin; Reid, Marvin; Chen, Diane D; Das, Partha Pratim; A Cole, Mitchel; Zeng, Jing; Kurita, Ryo; Nakamura, Yukio; Yuan, Guo-Cheng; Lettre, Guillaume; Bauer, Daniel E; Orkin, Stuart H

2017-04-01

Cas9-mediated, high-throughput, saturating in situ mutagenesis permits fine-mapping of function across genomic segments. Disease- and trait-associated variants identified in genome-wide association studies largely cluster at regulatory loci. Here we demonstrate the use of multiple designer nucleases and variant-aware library design to interrogate trait-associated regulatory DNA at high resolution. We developed a computational tool for the creation of saturating-mutagenesis libraries with single or multiple nucleases with incorporation of variants. We applied this methodology to the HBS1L-MYB intergenic region, which is associated with red-blood-cell traits, including fetal hemoglobin levels. This approach identified putative regulatory elements that control MYB expression. Analysis of genomic copy number highlighted potential false-positive regions, thus emphasizing the importance of off-target analysis in the design of saturating-mutagenesis experiments. Together, these data establish a widely applicable high-throughput and high-resolution methodology to identify minimal functional sequences within large disease- and trait-associated regions.

Multiple alpha subunits of integrin are involved in cell-mediated responses of the Manduca immune system.

PubMed

Zhuang, Shufei; Kelo, Lisha; Nardi, James B; Kanost, Michael R

2008-01-01

The cell-mediated responses of the insect innate immune system-phagocytosis, nodulation, encapsulation-involve multiple cell adhesion molecules of hemocyte surfaces. A hemocyte-specific (HS) integrin and a member of the immunoglobulin (Ig) superfamily (neuroglian) are involved in the encapsulation response of hemocytes in Manduca sexta. In addition, two new integrin alpha (alpha) subunits have been found on these hemocytes. The alpha2 subunit is mainly expressed in epidermis and Malphigian tubules, whereas the alpha3 subunit is primarily expressed on hemocytes and fat body cells. Of the three known alpha subunits, the alpha1 subunit found in HS integrin is the predominant subunit of hemocytes. Cell adhesion assays indicate that alpha2 belongs to the integrin family with RGD-binding motifs, confirming the phylogenetic analysis of alpha subunits based on the amino-acid sequence alignment of different alpha subunits. Double-stranded RNAs (dsRNAs) targeting each of these three integrin alpha subunits not only specifically decreased transcript expression of each alpha subunit in hemocytes, but also abolished the cell-mediated encapsulation response of hemocytes to foreign surfaces. The individual alpha subunits of M. sexta integrins, like their integrin counterparts in mammalian immune systems, have critical, individual roles in cell-substrate and cell-cell interactions during immune responses.

DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis.

PubMed

Kular, Lara; Liu, Yun; Ruhrmann, Sabrina; Zheleznyakova, Galina; Marabita, Francesco; Gomez-Cabrero, David; James, Tojo; Ewing, Ewoud; Lindén, Magdalena; Górnikiewicz, Bartosz; Aeinehband, Shahin; Stridh, Pernilla; Link, Jenny; Andlauer, Till F M; Gasperi, Christiane; Wiendl, Heinz; Zipp, Frauke; Gold, Ralf; Tackenberg, Björn; Weber, Frank; Hemmer, Bernhard; Strauch, Konstantin; Heilmann-Heimbach, Stefanie; Rawal, Rajesh; Schminke, Ulf; Schmidt, Carsten O; Kacprowski, Tim; Franke, Andre; Laudes, Matthias; Dilthey, Alexander T; Celius, Elisabeth G; Søndergaard, Helle B; Tegnér, Jesper; Harbo, Hanne F; Oturai, Annette B; Olafsson, Sigurgeir; Eggertsson, Hannes P; Halldorsson, Bjarni V; Hjaltason, Haukur; Olafsson, Elias; Jonsdottir, Ingileif; Stefansson, Kari; Olsson, Tomas; Piehl, Fredrik; Ekström, Tomas J; Kockum, Ingrid; Feinberg, Andrew P; Jagodic, Maja

2018-06-19

The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization provide evidence that HLA variants mediate risk for MS via changes in the HLA-DRB1 DMR that modify HLA-DRB1 expression. Meta-analysis of 14,259 cases and 171,347 controls confirms that these variants confer risk from DRB1*15:01 and also identifies a protective variant (rs9267649, p < 3.32 × 10 -8 , odds ratio = 0.86) after conditioning for all MS-associated variants in the region. rs9267649 is associated with increased DNA methylation at the HLA-DRB1 DMR and reduced expression of HLA-DRB1, suggesting a modulation of the DRB1*15:01 effect. Our integrative approach provides insights into the molecular mechanisms of MS susceptibility and suggests putative therapeutic strategies targeting a methylation-mediated regulation of the major risk gene.

Pervasive gene expression responses to a fluctuating diet in Drosophila melanogaster: The importance of measuring multiple traits to decouple potential mediators of life span and reproduction.

PubMed

Zandveld, Jelle; van den Heuvel, Joost; Mulder, Maarten; Brakefield, Paul M; Kirkwood, Thomas B L; Shanley, Daryl P; Zwaan, Bas J

2017-11-01

Phenotypic plasticity is an important concept in life-history evolution, and most organisms, including Drosophila melanogaster, show a plastic life-history response to diet. However, little is known about how these life-history responses are mediated. In this study, we compared adult female flies fed an alternating diet (yoyo flies) with flies fed a constant low (CL) or high (CH) diet and tested how whole genome expression was affected by these diet regimes and how the transcriptional responses related to different life-history traits. We showed that flies were able to respond quickly to diet fluctuations throughout life span by drastically changing their transcription. Importantly, by measuring the response of multiple life-history traits we were able to decouple groups of genes associated with life span or reproduction, life-history traits that often covary with a diet change. A coexpression network analysis uncovered which genes underpin the separate and shared regulation of these life-history traits. Our study provides essential insights to help unravel the genetic architecture mediating life-history responses to diet, and it shows that the flies' whole genome transcription response is highly plastic. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Salicylic acid is an indispensable component of the Ny-1 resistance-gene-mediated response against Potato virus Y infection in potato

PubMed Central

Baebler, Š.; Witek, K.; Gruden, K.; Hennig, J.

2014-01-01

The purpose of the study was to investigate the role of salicylic acid (SA) signalling in Ny-1-mediated hypersensitive resistance (HR) of potato (Solanum tuberosum L.) to Potato virus Y (PVY). The responses of the Ny-1 allele in the Rywal potato cultivar and transgenic NahG-Rywal potato plants that do not accumulate SA were characterized at the cytological, biochemical, transcriptome, and proteome levels. Analysis of noninoculated and inoculated leaves revealed that HR lesions started to develop from 3 d post inoculation and completely restricted the virus spread. At the cytological level, features of programmed cell death in combination with reactive oxygen species burst were observed. In response to PVY infection, SA was synthesized de novo. The lack of SA accumulation in the NahG plants led to the disease phenotype due to unrestricted viral spreading. Grafting experiments show that SA has a critical role in the inhibition of PVY spreading in parenchymal tissue, but not in vascular veins. The whole transcriptome analysis confirmed the central role of SA in orchestrating Ny-1-mediated responses and showed that the absence of SA leads to significant changes at the transcriptome level, including a delay in activation of expression of genes known to participate in defence responses. Moreover, perturbations in the expression of hormonal signalling genes were detected, shown as a switch from SA to jasmonic acid/ethylene signalling. Viral multiplication in the NahG plants was accompanied by downregulation of photosynthesis genes and activation of multiple energy-producing pathways. PMID:24420577

Salicylic acid is an indispensable component of the Ny-1 resistance-gene-mediated response against Potato virus Y infection in potato.

PubMed

Baebler, Š; Witek, K; Petek, M; Stare, K; Tušek-Žnidarič, M; Pompe-Novak, M; Renaut, J; Szajko, K; Strzelczyk-Żyta, D; Marczewski, W; Morgiewicz, K; Gruden, K; Hennig, J

2014-03-01

The purpose of the study was to investigate the role of salicylic acid (SA) signalling in Ny-1-mediated hypersensitive resistance (HR) of potato (Solanum tuberosum L.) to Potato virus Y (PVY). The responses of the Ny-1 allele in the Rywal potato cultivar and transgenic NahG-Rywal potato plants that do not accumulate SA were characterized at the cytological, biochemical, transcriptome, and proteome levels. Analysis of noninoculated and inoculated leaves revealed that HR lesions started to develop from 3 d post inoculation and completely restricted the virus spread. At the cytological level, features of programmed cell death in combination with reactive oxygen species burst were observed. In response to PVY infection, SA was synthesized de novo. The lack of SA accumulation in the NahG plants led to the disease phenotype due to unrestricted viral spreading. Grafting experiments show that SA has a critical role in the inhibition of PVY spreading in parenchymal tissue, but not in vascular veins. The whole transcriptome analysis confirmed the central role of SA in orchestrating Ny-1-mediated responses and showed that the absence of SA leads to significant changes at the transcriptome level, including a delay in activation of expression of genes known to participate in defence responses. Moreover, perturbations in the expression of hormonal signalling genes were detected, shown as a switch from SA to jasmonic acid/ethylene signalling. Viral multiplication in the NahG plants was accompanied by downregulation of photosynthesis genes and activation of multiple energy-producing pathways.

Paternal involvement and early infant neurodevelopment: the mediation role of maternal parenting stress.

PubMed

Kim, Minjeong; Kang, Su-Kyoung; Yee, Bangsil; Shim, So-Yeon; Chung, Mira

2016-12-12

Father-child interactions are associated with improved developmental outcomes among infants. However, to the best of our knowledge, no study has addressed the effects of paternal involvement on the neurodevelopment of infants who are less than 6 months of age, and no study has reported how maternal parenting stress mediates the relationship between paternal involvement and infant neurodevelopment during early infancy. This study investigates the direct and indirect relationship between paternal involvement and infant neurodevelopment at 3-4 months of age. The indirect relationship was assessed through the mediating factor of maternal parenting stress. The participants were recruited through the Sesalmaul Research Center's website from April to June 2014. The final data included 255 mothers and their healthy infants, who were aged 3-4 months. The mothers reported paternal involvement and maternal parenting stress by using Korean Parenting Alliance Inventory (K-PAI) and Parenting Stress Index (PSI), respectively. Experts visited the participants' homes to observe infant neurodevelopment, and completed a developmental examination using Korean version of the Ages and Stages Questionnaire II (K-ASQ II). A hierarchical multiple regression analysis was used for data analysis. Infants' mean ages were 106 days and girls accounted for 46.3%. The mean total scores (reference range) of the K-PAI, PSI, and the K-ASQ II were 55.5 (17-68), 45.8 (25-100), and 243.2 (0-300), respectively. Paternal involvement had a positive relationship with K-ASQ II scores (β = 0.29, p < 0.001) at 3-4 months of age, whereas maternal parenting stress was negatively related with K-ASQ II scores (β = -0.32, p < 0.001). Maternal parenting stress mediated the relationship between paternal involvement and early infant neurodevelopment (Z = 3.24, p < 0.001). A hierarchical multiple regression analysis showed that paternal involvement reduced maternal parenting stress (β = -0.25, p < 0.001), which led to positive infant outcomes (β = 0.23, p < 0.001). Paternal involvement is significantly associated with infant neurodevelopment during early infancy, and maternal parenting stress partially mediates that association. This result emphasizes the importance of fathers' involvement and mothers' parenting stress on early infant neurodevelopment.

Methods for extracting social network data from chatroom logs

NASA Astrophysics Data System (ADS)

Osesina, O. Isaac; McIntire, John P.; Havig, Paul R.; Geiselman, Eric E.; Bartley, Cecilia; Tudoreanu, M. Eduard

2012-06-01

Identifying social network (SN) links within computer-mediated communication platforms without explicit relations among users poses challenges to researchers. Our research aims to extract SN links in internet chat with multiple users engaging in synchronous overlapping conversations all displayed in a single stream. We approached this problem using three methods which build on previous research. Response-time analysis builds on temporal proximity of chat messages; word context usage builds on keywords analysis and direct addressing which infers links by identifying the intended message recipient from the screen name (nickname) referenced in the message [1]. Our analysis of word usage within the chat stream also provides contexts for the extracted SN links. To test the capability of our methods, we used publicly available data from Internet Relay Chat (IRC), a real-time computer-mediated communication (CMC) tool used by millions of people around the world. The extraction performances of individual methods and their hybrids were assessed relative to a ground truth (determined a priori via manual scoring).

Monoterpene and sesquiterpene synthases and the origin of terpene skeletal diversity in plants.

PubMed

Degenhardt, Jörg; Köllner, Tobias G; Gershenzon, Jonathan

2009-01-01

The multitude of terpene carbon skeletons in plants is formed by enzymes known as terpene synthases. This review covers the monoterpene and sesquiterpene synthases presenting an up-to-date list of enzymes reported and evidence for their ability to form multiple products. The reaction mechanisms of these enzyme classes are described, and information on how terpene synthase proteins mediate catalysis is summarized. Correlations between specific amino acid motifs and terpene synthase function are described, including an analysis of the relationships between active site sequence and cyclization type and a discussion of whether specific protein features might facilitate multiple product formation.

Exercise, Diet, and Stress Management as Mediators between Functional Disability and Health-Related Quality of Life in Multiple Sclerosis

ERIC Educational Resources Information Center

Sung, Connie; Chiu, Chung-Yi; Lee, Eun-Jeong; Bezyak, Jill; Chan, Fong; Muller, Veronica

2013-01-01

The main objective of this study was to examine the mediational and moderational effect of exercise, diet, and stress management on the relationship between functional disability and health-related quality of life. Quantitative descriptive research design using multiple regression and correlation techniques was used. Participants were 215…

The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

ERIC Educational Resources Information Center

Cheng, Ying; Shao, Can; Lathrop, Quinn N.

2016-01-01

Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

Ethnic and Racial Socialization and Self-Esteem of Asian Adoptees: The Mediating Role of Multiple Identities

ERIC Educational Resources Information Center

Mohanty, Jayashree

2013-01-01

Positive identity development during adolescence in general is a complex process and may pose additional challenges for adolescents adopted from a different culture. Using a web-based survey design with a sample of 100 internationally adopted Asian adolescent and young adults, the present study examined the mediating role of multiple identities…

Beyond group engagement: Multiple pathways from encounters with the police to cooperation and compliance in Northern Ireland

PubMed Central

Devaney, Lee; Bryan, Dominic; Blaylock, Danielle L.

2017-01-01

In a sample of young people in Northern Ireland (N = 819), we examine the relationships between the quality of experience with police officers and police legitimacy. We examine potential pathways through which experiences may either support or undermine the legitimacy of the police, and thus cooperation and compliance with them. We find evidence that perceptions of the police as having goals that align with those of wider society, and as being fair in general, mediate relations between the quality of encounters and legitimacy, which in turn mediates the relation with cooperation and compliance. Identification with wider society was not a reliable mediator, contrary to our predictions based on the Group Engagement Model. Moreover, our analysis of the structure of police fairness perceptions finds no support for the distinction between procedural and distributive police fairness as usually conceived. Implications for the social psychological understanding of legitimate authority are discussed. PMID:28880946

Beyond group engagement: Multiple pathways from encounters with the police to cooperation and compliance in Northern Ireland.

PubMed

Pehrson, Samuel; Devaney, Lee; Bryan, Dominic; Blaylock, Danielle L

2017-01-01

In a sample of young people in Northern Ireland (N = 819), we examine the relationships between the quality of experience with police officers and police legitimacy. We examine potential pathways through which experiences may either support or undermine the legitimacy of the police, and thus cooperation and compliance with them. We find evidence that perceptions of the police as having goals that align with those of wider society, and as being fair in general, mediate relations between the quality of encounters and legitimacy, which in turn mediates the relation with cooperation and compliance. Identification with wider society was not a reliable mediator, contrary to our predictions based on the Group Engagement Model. Moreover, our analysis of the structure of police fairness perceptions finds no support for the distinction between procedural and distributive police fairness as usually conceived. Implications for the social psychological understanding of legitimate authority are discussed.

Investigation of the Structural Relationships Between Social Support, Self-Compassion, and Subjective Well-Being in Korean Elite Student Athletes.

PubMed

Jeon, Hyunsoo; Lee, Keunchul; Kwon, Sungho

2016-08-01

The study examined whether self-compassion mediates the relationship between social support and subjective well-being, as perceived by athletes. It also investigated the structural relationships between these variables. Participants were 333 athletes attending high school or university. Structural equation analysis showed that self-compassion partially mediated the relationship between social support and subjective well-being. To test the stability of the model, a multiple group analysis was performed according to sex of participant and school level, and this demonstrated that the model had similar fit to the data regardless of group. The confirmation that self-compassion plays an intermediary role in the relationship between social support and subjective well-being demonstrates that self-compassionate attitudes can be fostered by social support, and that, in turn, has a positive effect on an individual's subjective well-being. © The Author(s) 2016.

Impact of job characteristics on psychological health of Chinese single working women.

PubMed

Yeung, D Y; Tang, C S

2001-01-01

This study aims at investigating the impact of individual and contextual job characteristics of control, psychological and physical demand, and security on psychological distress of 193 Chinese single working women in Hong Kong. The mediating role of job satisfaction in the job characteristics-distress relation is also assessed. Multiple regression analysis results show that job satisfaction mediates the effects of job control and security in predicting psychological distress; whereas psychological job demand has an independent effect on mental distress after considering the effect of job satisfaction. This main effect model indicates that psychological distress is best predicted by small company size, high psychological job demand, and low job satisfaction. Results from a separate regression analysis fails to support the overall combined effect of job demand-control on psychological distress. However, a significant physical job demand-control interaction effect on mental distress is noted, which reduces slightly after controlling the effect of job satisfaction.

Working Memory and Cognitive Flexibility Mediates Visuoconstructional Abilities in Older Adults with Heterogeneous Cognitive Ability.

PubMed

Ávila, Rafaela T; de Paula, Jonas J; Bicalho, Maria A; Moraes, Edgar N; Nicolato, Rodrigo; Malloy-Diniz, Leandro F; Diniz, Breno S

2015-05-01

Previous studies suggest that executive functions influence the performance on visuoconstructional tasks. This study aims to investigate whether the relationship between planning ability and the copy of complex figures is mediated by distinct components of executive functions (i.e., working memory, inhibitory control and cognitive flexibility). We included a 129 older adults with Alzheimer's disease (n=36, AD), mild cognitive impairment (MCI, n=67), and with no evidence of cognitive impairment (controls, n=26). We evaluated the mediation effect of planning abilities, working memory, cognitive flexibility and inhibitory control on visuoconstructional tasks using a multiple mediation models. We found a significant direct effect of planning on visuoconstructional abilities and a partial mediation effect of working memory and cognitive flexibility on visuoconstructional abilities. The present results indicate that the performance on visuoconstructional task is mediated by multiple interrelated executive functions components, in particular working memory and cognitive flexibility.

Dispositional optimism and sleep quality: a test of mediating pathways

PubMed Central

Cribbet, Matthew; Kent de Grey, Robert G.; Cronan, Sierra; Trettevik, Ryan; Smith, Timothy W.

2016-01-01

Dispositional optimism has been related to beneficial influences on physical health outcomes. However, its links to global sleep quality and the psychological mediators responsible for such associations are less studied. This study thus examined if trait optimism predicted global sleep quality, and if measures of subjective well-being were statistical mediators of such links. A community sample of 175 participants (93 men, 82 women) completed measures of trait optimism, depression, and life satisfaction. Global sleep quality was assessed using the Pittsburgh Sleep Quality Index. Results indicated that trait optimism was a strong predictor of better PSQI global sleep quality. Moreover, this association was mediated by depression and life satisfaction in both single and multiple mediator models. These results highlight the importance of optimism for the restorative process of sleep, as well as the utility of multiple mediator models in testing distinct psychological pathways. PMID:27592128

Dispositional optimism and sleep quality: a test of mediating pathways.

PubMed

Uchino, Bert N; Cribbet, Matthew; de Grey, Robert G Kent; Cronan, Sierra; Trettevik, Ryan; Smith, Timothy W

2017-04-01

Dispositional optimism has been related to beneficial influences on physical health outcomes. However, its links to global sleep quality and the psychological mediators responsible for such associations are less studied. This study thus examined if trait optimism predicted global sleep quality, and if measures of subjective well-being were statistical mediators of such links. A community sample of 175 participants (93 men, 82 women) completed measures of trait optimism, depression, and life satisfaction. Global sleep quality was assessed using the Pittsburgh Sleep Quality Index. Results indicated that trait optimism was a strong predictor of better PSQI global sleep quality. Moreover, this association was mediated by depression and life satisfaction in both single and multiple mediator models. These results highlight the importance of optimism for the restorative process of sleep, as well as the utility of multiple mediator models in testing distinct psychological pathways.

Conceptual development and retention within the learning cycle

NASA Astrophysics Data System (ADS)

McWhirter, Lisa Jo

1998-12-01

This research was designed to achieve two goals: (1) examine concept development and retention within the learning cycle and (2) examine how students' concept development is mediated by classroom discussions and the students' small cooperative learning group. Forty-eight sixth-grade students and one teacher at an urban middle school participated in the study. The research utilized both quantitative and qualitative analyses. Quantitative assessments included a concept mapping technique as well as teacher generated multiple choice tests. Preliminary quantitative analysis found that students' reading levels had an effect on students' pretest scores in both the concept mapping and the multiple-choice assessment. Therefore, a covariant design was implemented for the quantitative analyses. Quantitative analysis techniques were used to examine concept development and retention, it was discovered that the students' concept knowledge increased significantly from the time of the conclusion of the term introduction phase to the conclusion of the expansion phase. These findings would indicate that all three phases of the learning cycle are necessary for conceptual development. However, quantitative analyses of concept maps indicated that this is not true for all students. Individual students showed evidence of concept development and integration at each phase. Therefore, concept development is individualized and all phases of the learning cycle are not necessary for all students. As a result, individual's assimilation, disequilibration, accommodation and organization may not correlate with the phases of the learning cycle. Quantitative analysis also indicated a significant decrease in the retention of concepts over time. Qualitative analyses were used to examine how students' concept development is mediated by classroom discussions and the students' small cooperative learning group. It was discovered that there was a correlation between teacher-student interaction and small-group interaction and concept mediation. Therefore, students who had a high level of teacher-student dialogue which utilized teacher led discussions with integrated scaffolding techniques where the same students who mediated the ideas within the small group discussions. Those students whose teacher-student interactions consisted of dialogue with little positive teacher feedback made no contributions within the small group regardless of their level of concept development.

Explaining the relationship between attachment anxiety, eating behaviour and BMI.

PubMed

Wilkinson, Laura L; Rowe, Angela C; Robinson, Eric; Hardman, Charlotte A

2018-05-05

Previous research indicates that attachment anxiety (fear of abandonment) is predictive of overeating and higher body mass index (BMI). The current study explored the nature of the mechanisms underpinning this relationship. Study 1 assessed the relative contribution of 'emotional eating', 'susceptibility to hunger' and 'uncontrolled eating'. Study 2 assessed whether misperception of emotion and poor emotion management would mediate the relationship between attachment anxiety and stress-induced eating (and then BMI). Two cross-sectional online questionnaire studies were conducted (Study 1 N = 665, & Study 2 N = 548), in UK and US-based samples, which assessed attachment orientation and BMI alongside the potential mediators. The relative contribution of emotional eating, susceptibility to hunger and uncontrolled eating (Study 1) and difficulties in emotion regulation and stress-induced eating (Study 2) as mediators of this relationship were examined. In Study 1, parallel multiple mediation analysis (PROCESS) showed that emotional eating and susceptibility to hunger (but not uncontrolled eating) were significant mediators of the relationship between attachment anxiety and BMI. In Study 2, serial mediation analysis showed that difficulties in 'engaging with goal directed behaviours when upset' and stress-induced eating operated in series to significantly mediate the relationship between attachment anxiety and BMI. These findings suggest that attachment anxious individuals feel less capable in disengaging from negative emotions and go on to try to soothe themselves through eating which has a negative impact on their BMI. There was less support for an explanation of the relationship between attachment anxiety and BMI based around the misperception of emotion. Taken together, the findings highlight attachment anxiety and emotion regulation strategies as key targets for interventions that aim to reduce overeating and excess body weight. Copyright © 2018 Elsevier Ltd. All rights reserved.

Emergency room nurses' pathway to turnover intention: a moderated serial mediation analysis.

PubMed

Bruyneel, Luk; Thoelen, Tom; Adriaenssens, Jef; Sermeus, Walter

2017-04-01

The aim of this study was to explore the association between the quality of the work environment, job characteristics, demographic characteristics and a pathway of job satisfaction, emotional exhaustion and turnover intention among nurses in emergency departments and perform subgroup analyses. Turnover intention among nurses is high. Multiple causes have been described, mostly in large studies of nurses working on general wards, often without considering complementarity of conceptual models and showing scant interest in the consistency of associations across subgroups of nurses. Cross-sectional multicentre survey. Convenience sample of 294 nurses in 11 Belgian emergency departments during 2014-2015. Indirect effects in the form of mediation and serial mediation were estimated to assess the association between work environment (Magnet model), job characteristics (Job Demand Control Support model) and turnover intention via job satisfaction and emotional exhaustion. Consistency of these indirect effects across subgroups of nurses was examined using moderated mediation analysis (conditional indirect effects). Several Magnet and Job Demand Control Support dimensions were related to turnover intention, either via job dissatisfaction (mediation) or via job satisfaction and emotional exhaustion (serial mediation). In the case of social support from supervisor, these indirect effects were only significant for female nurses, among whom turnover intention was higher. Last, nurses with more years of experience were less likely to indicate turnover intention. To maximize prevention of turnover intention at emergency departments, interventions could target early career nurses, work environment and job characteristics. Female nurses in particular may also benefit from improved social support from their supervisor. © 2016 John Wiley & Sons Ltd.

A multiple mediational test of the relationship between childhood maltreatment and non-suicidal self-injury.

PubMed

Shenk, Chad E; Noll, Jennie G; Cassarly, Jennifer A

2010-04-01

Post-traumatic stress symptoms, depressive symptoms, and psychological dysregulation have been shown to mediate the relationship between child maltreatment and non-suicidal self-injury. However, these proposed mediators often co-occur and previous research has not tested mediation when all variables are assessed simultaneously. The current study sought to advance the literature on maltreatment and self-injury by estimating the mediational effects of post-traumatic stress symptoms, depressive symptoms, and psychological dysregulation in the same multiple mediator model. Both maltreated (n = 129) and non-maltreated (n = 82) adolescent females, consisting of Caucasian (55%), African-American (37%), and Bi-racial (8%) backgrounds, participated in the study. Results indicated that only post-traumatic stress symptoms mediated the relationship between maltreatment and self-injury when all variables were included in the model. Overall, post-traumatic symptoms represented a unique pathway from maltreatment to self-injury and warrant special attention when assessing and treating such behavior with adolescent females.

Development of efficient plant regeneration and transformation system for impatiens using Agrobacterium tumefaciens and multiple bud cultures as explants.

PubMed

Dan, Yinghui; Baxter, Aaron; Zhang, Song; Pantazis, Christopher J; Veilleux, Richard E

2010-08-09

Impatiens (Impatiens walleriana) is a top selling floriculture crop. The potential for genetic transformation of Impatiens to introduce novel flower colors or virus resistance has been limited by its general recalcitrance to tissue culture and transformation manipulations. We have established a regeneration and transformation system for Impatiens that provides new alternatives to genetic improvement of this crop. In a first step towards the development of transgenic INSV-resistant Impatiens, we developed an efficient plant regeneration system using hypocotyl segments containing cotyledonary nodes as explants. With this regeneration system, 80% of explants produced an average of 32.3 elongated shoots per initial explant plated, with up to 167 elongated shoots produced per explant. Rooting efficiency was high, and 100% of shoots produced roots within 12 days under optimal conditions, allowing plant regeneration within approximately 8 weeks. Using this regeneration system, we developed an efficient Agrobacterium-mediated Impatiens transformation method using in vitro multiple bud cultures as explants and a binary plasmid (pHB2892) bearing gfp and nptII genes. Transgenic Impatiens plants, with a frequency up to 58.9%, were obtained within 12 to 16 weeks from inoculation to transfer of transgenic plants to soil. Transgenic plants were confirmed by Southern blot, phenotypic assays and T1 segregation analysis. Transgene expression was observed in leaves, stems, roots, flowers, and fruit. The transgenic plants were fertile and phenotypically normal. We report the development of a simple and efficient Agrobacterium-mediated transformation system for Impatiens. To the best of our knowledge, there have been no reports of Agrobacterium-mediated transformation of Impatiens with experimental evidence of stable integration of T-DNA and of Agrobacterium-mediated transformation method for plants using in vitro maintained multiple bud cultures as explants. This transformation system has the advantages of 1) efficient, simple and rapid regeneration and transformation (with no need for sterilization or a greenhouse to grow stock plants), 2) flexibility (available all the time) for in vitro manipulation, 3) uniform and desirable green tissue explants for both nuclear and plastid transformation using Agrobacterium-mediated and biolistics methods, 4) no somaclonal variation and 5) resolution of necrosis of Agrobacterium-inoculated tissues.

Mediators of improved child diet quality following a health promotion intervention: the Melbourne InFANT Program.

PubMed

Spence, Alison C; Campbell, Karen J; Crawford, David A; McNaughton, Sarah A; Hesketh, Kylie D

2014-11-04

Young children's diets are currently suboptimal. Given that mothers have a critical influence on children' diets, they are typically a target of interventions to improve early childhood nutrition. Understanding the maternal factors which mediate an intervention's effect on young children's diets is important, but has not been well investigated. This research aimed to test whether maternal feeding knowledge, maternal feeding practices, maternal self-efficacy, and maternal dietary intakes acted as mediators of the effect of an intervention to improve child diet quality. The Melbourne Infant Feeding Activity and Nutrition Trial (InFANT) Program was a cluster-randomized controlled trial, conducted from 2008-2010. This novel, low-dose, health promotion intervention was delivered quarterly over 15 months and involved educational activities, promotion of peer discussion, a DVD and written materials. Post-intervention, when children were approximately 18 months of age, child diets were assessed using multiple 24-hour recalls and a purpose-developed index of diet quality, the Obesity Protective Dietary Index. Maternal mediators were assessed using a combination of previously validated and purpose-deigned tools. Mediation analysis was conducted using the test of joint significance and difference of coefficients methods. Across 62 parents' groups in Melbourne, Australia, 542 parents were recruited. Post- intervention, higher maternal feeding knowledge and lower use of foods as rewards was found to mediate the direct intervention effect on child diet quality. While other aspects of maternal feeding practices, self-efficacy and dietary intakes did not act as mediators, they were associated with child diet quality. Mediation analysis of this novel health promotion intervention showed the importance of maternal feeding knowledge and use of foods as rewards in impacting child diet quality. The other maternal factors assessed were appropriate targets but further research on how to impact these in an intervention is important. This evidence of intervention efficacy and mediation provides important insights for planning future interventions. Current Controlled Trials ISRCTN81847050, registered 23 November 2007.

Serial Multiple Mediation of General Belongingness and Life Satisfaction in the Relationship between Attachment and Loneliness in Adolescents

ERIC Educational Resources Information Center

Yildiz, Mehmet Ali

2016-01-01

The current research aims to investigate the serial-multiple mediation of general belongingness and life satisfaction in the relationship between loneliness and attachment to parents and peers in adolescents. The participants of the research consisted of 218 high school students (F = 126, 57.8%; M = 92, 42.2%). Age of the participants' ranged…

A Knowledge-Modeling Approach to Integrate Multiple Clinical Practice Guidelines to Provide Evidence-Based Clinical Decision Support for Managing Comorbid Conditions.

PubMed

Abidi, Samina

2017-10-26

Clinical management of comorbidities is a challenge, especially in a clinical decision support setting, as it requires the safe and efficient reconciliation of multiple disease-specific clinical procedures to formulate a comorbid therapeutic plan that is both effective and safe for the patient. In this paper we pursue the integration of multiple disease-specific Clinical Practice Guidelines (CPG) in order to manage co-morbidities within a computerized Clinical Decision Support System (CDSS). We present a CPG integration framework-termed as COMET (Comorbidity Ontological Modeling & ExecuTion) that manifests a knowledge management approach to model, computerize and integrate multiple CPG to yield a comorbid CPG knowledge model that upon execution can provide evidence-based recommendations for handling comorbid patients. COMET exploits semantic web technologies to achieve (a) CPG knowledge synthesis to translate a paper-based CPG to disease-specific clinical pathways (CP) that include specialized co-morbidity management procedures based on input from domain experts; (b) CPG knowledge modeling to computerize the disease-specific CP using a Comorbidity CPG ontology; (c) CPG knowledge integration by aligning multiple ontologically-modeled CP to develop a unified comorbid CPG knowledge model; and (e) CPG knowledge execution using reasoning engines to derive CPG-mediated recommendations for managing patients with comorbidities. We present a web-accessible COMET CDSS that provides family physicians with CPG-mediated comorbidity decision support to manage Atrial Fibrillation and Chronic Heart Failure. We present our qualitative and quantitative analysis of the knowledge content and usability of COMET CDSS.

A Multiple Mediational Test of the Relationship between Childhood Maltreatment and Non-Suicidal Self-Injury

ERIC Educational Resources Information Center

Shenk, Chad E.; Noll, Jennie G.; Cassarly, Jennifer A.

2010-01-01

Post-traumatic stress symptoms, depressive symptoms, and psychological dysregulation have been shown to mediate the relationship between child maltreatment and non-suicidal self-injury. However, these proposed mediators often co-occur and previous research has not tested mediation when all variables are assessed simultaneously. The current study…

Stress and multiple sclerosis: A systematic review considering potential moderating and mediating factors and methods of assessing stress.

PubMed

Briones-Buixassa, Laia; Milà, Raimon; Mª Aragonès, Josep; Bufill, Enric; Olaya, Beatriz; Arrufat, Francesc Xavier

2015-07-01

Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science), Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms "stress*" AND "multiple sclerosis." Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset ( n  = 9) were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression ( n  = 14) were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis.

Stress and multiple sclerosis: A systematic review considering potential moderating and mediating factors and methods of assessing stress

PubMed Central

Briones-Buixassa, Laia; Milà, Raimon; Mª Aragonès, Josep; Bufill, Enric; Olaya, Beatriz; Arrufat, Francesc Xavier

2015-01-01

Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science), Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms “stress*” AND “multiple sclerosis.” Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset (n = 9) were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression (n = 14) were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis. PMID:28070374

Testing a multiple mediator model of the effect of childhood sexual abuse on adolescent sexual victimization.

PubMed

Bramsen, Rikke H; Lasgaard, Mathias; Koss, Mary P; Shevlin, Mark; Elklit, Ask; Banner, Jytte

2013-01-01

The present study modeled the direct relationship between child sexual abuse (CSA) and adolescent peer-to-peer sexual victimization (APSV) and the mediated effect via variables representing the number of sexual partners, sexual risk behavior, and signaling sexual boundaries. A cross-sectional study on the effect of CSA on APSV was conducted, utilizing a multiple mediator model. Mediated and direct effects in the model were estimated employing Mplus using bootstrapped percentile based confidence intervals to test for significance of mediated effects. The study employed 327 Danish female adolescents with a mean age of 14.9 years (SD = 0.5). The estimates from the mediational model indicated full mediation of the effect of CSA on APSV via number of sexual partners and sexual risk behavior. The current study suggests that the link between CSA and APSV was mediated by sexual behaviors specifically pertaining to situations of social peer interaction, rather than directly on prior experiences of sexual victimization. The present study identifies a modifiable target area for intervention to reduce adolescent sexual revictimization. © 2013 American Orthopsychiatric Association.

Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis.

PubMed

Schmidt, S; Pericak-Vance, M A; Sawcer, S; Barcellos, L F; Hart, J; Sims, J; Prokop, A M; van der Walt, J; DeLoa, C; Lincoln, R R; Oksenberg, J R; Compston, A; Hauser, S L; Haines, J L; Gregory, S G

2006-07-01

Discrepant findings have been reported regarding an association of the apolipoprotein E (APOE) gene with the clinical course of multiple sclerosis (MS). To resolve these discrepancies, we examined common sequence variation in six candidate genes residing in a 380-kb genomic region surrounding and including the APOE locus for an association with MS severity. We genotyped at least three polymorphisms in each of six candidate genes in 1,540 Caucasian MS families (729 single-case and multiple-case families from the United States, 811 single-case families from the UK). By applying the quantitative transmission/disequilibrium test to a recently proposed MS severity score, the only statistically significant (P=0.003) association with MS severity was found for an intronic variant in the Herpes Virus Entry Mediator-B Gene PVRL2. Additional genotyping extended the association to a 16.6 kb block spanning intron 1 to intron 2 of the gene. Sequencing of PVRL2 failed to identify variants with an obvious functional role. In conclusion, the analysis of a very large data set suggests that genetic polymorphisms in PVRL2 may influence MS severity and supports the possibility that viral factors may contribute to the clinical course of MS, consistent with previous reports.

Effects of the Educational Leadership of Nursing Unit Managers on Team Effectiveness: Mediating Effects of Organizational Communication.

PubMed

Choi, Eun Ha; Kim, Eun-Kyung; Kim, Pil Bong

2018-03-31

EDUCATIONAL LEADERSHIP OF NURSING UNIT MANAGERS ON TEAM EFFECTIVENESS: Mediating Effects of Organizational Communication Satisfaction. This study identifies the effects of the educational leadership of nursing unit managers on team effectiveness and the mediating effects of organizational communication satisfaction; it highlights the importance of educational leadership and organizational communication and provides the data needed to enhance the education capacity of managers. The participants were 216 nursing unit managers of staff nurses at a tertiary hospital located in C Region, South Korea, and nurses who had worked for more than six months at the same hospital. This study was conducted using questionnaires on educational leadership, team effectiveness, and organizational communication satisfaction. Data analysis was performed with a t-test, ANOVA, Scheffé, Pearson's correlation coefficient, and simple and multiple regression analyses using SPSS version 23.0. Mediation analysis was tested using Baron and Kenny's regression analysis and a Sobel test. The mean score for the educational leadership of nursing unit managers was 3.74(±0.68); for organizational communication satisfaction, 3.14(±0.51); and for team effectiveness, 3.52(±0.49). Educational leadership was significantly positively correlated with team effectiveness and organizational communication satisfaction. Organizational communication satisfaction demonstrated a complete mediating effect on the relationship between educational leadership and team effectiveness (β=.61, p<.001) and was significant (Sobel test; Z=7.40, p<.001). The results indicate that the educational leadership of nursing unit managers increases communication satisfaction among nurses; this supports the idea that educational leadership can contribute to team effectiveness. This suggests that the educational leadership and communication capacity of nursing unit managers must be improved to enhance the performance of nursing organizations. Copyright © 2018. Published by Elsevier B.V.

Parental bonding and eating psychopathology in bulimia nervosa: personality traits as possible mediators.

PubMed

Fassino, Secondo; Amianto, Federico; Rocca, Giuseppe; Daga, Giovanni Abbate

2010-01-01

The relationship between eating disorders, attachment, personality traits and eating psychopathology remains unexplored. This study tested the mediating role of temperament and character between parental bonding and psychopathology in bulimic women. 154 bulimic subjects and 154 healthy controls were compared using Parental Bonding Instrument (PBI), Temperament and Character Inventory (TCI), Eating Disorder Inventory-2 (EDI-2), and Beck Depression Inventory (BDI). Multiple regression analysis tested the mediation of personality traits between parenting and eating psychopathology. Bulimic subjects displayed low maternal and paternal care and low self-directedness, and high novelty seeking and eating psychopathology. Maternal care was negatively related to social insecurity, inadequacy and impulsiveness. Paternal care predicted novelty seeking, self-directedness, interoceptive awareness, impulsiveness, and asceticism. The mediation effect of self-directedness between paternal care and psychopathology was significant, not the one of novelty seeking. Parental care is lower in bulimic than in control women even when controlled for possible confounding variables. Some eating psychopathology traits are related to maternal and paternal care, but not the bulimia subscale. Paternal care is also related to temperament and character traits which are related to eating psychopathology. Self-directedness mediates with different degrees between parenting and eating psychopathology. Clinical implications are discussed.

Mediating relationship of differential products in understanding integration in introductory physics

NASA Astrophysics Data System (ADS)

Amos, Nathaniel; Heckler, Andrew F.

2018-01-01

In the context of introductory physics, we study student conceptual understanding of differentials, differential products, and integrals and possible pathways to understanding these quantities. We developed a multiple choice conceptual assessment employing a variety of physical contexts probing physical understanding of these three quantities and administered the instrument to over 1000 students in first and second semester introductory physics courses. Using a regression-based mediation analysis with conceptual understanding of integration as the dependent variable, we found evidence consistent with a simple mediation model: the relationship between differentials scores and integral scores may be mediated by the understanding of differential products. The indirect effect (a quantifiable metric of mediation) was estimated as a b =0.29 , 95% CI [0.25, 0.33] for N =1102 Physics 1 students, and a b =0.27 , 95% CI [0.14, 0.48] for N =65 Physics 2 students. We also find evidence that the physical context of the questions can be an important factor. These results imply that for introductory physics courses, instructional emphasis first on differentials then on differential products in a variety of contexts may in turn promote better integral understanding.

Molecular study on some antibiotic resistant genes in Salmonella spp. isolates

NASA Astrophysics Data System (ADS)

Nabi, Ari Q.

2017-09-01

Studying the genes related with antimicrobial resistance in Salmonella spp. is a crucial step toward a correct and faster treatment of infections caused by the pathogen. In this work Integron mediated antibiotic resistant gene IntI1 (Class I Integrase IntI1) and some plasmid mediated antibiotic resistance genes (Qnr) were scanned among the isolated non-Typhoid Salmonellae strains with known resistance to some important antimicrobial drugs using Sybr Green real time PCR. The aim of the study was to correlate the multiple antibiotics and antimicrobial resistance of Salmonella spp. with the presence of integrase (IntI1) gene and plasmid mediated quinolone resistant genes. Results revealed the presence of Class I Integrase gene in 76% of the isolates with confirmed multiple antibiotic resistances. Moreover, about 32% of the multiple antibiotic resistant serotypes showed a positive R-PCR for plasmid mediated qnrA gene encoding for nalidixic acid and ciprofloxacin resistance. No positive results could be revealed form R-PCRs targeting qnrB or qnrS. In light of these results we can conclude that the presence of at least one of the qnr genes and/or the presence of Integrase Class I gene were responsible for the multiple antibiotic resistance to for nalidixic acid and ciprofloxacin from the studied Salmonella spp. and further studies required to identify the genes related with multiple antibiotic resistance of the pathogen.

In vitro transfer of multiple resistance observed in vivo during a Salmonella london epidemic.

PubMed

Lantos, J; Marjai, E

1980-01-01

Between 1976 and 1978, waves of Salmonella london infections conveyed by raw meat and meat products were observed. The strains isolated during the epidemic were first susceptible then developed multiple antibiotic resistance. The identical antibiotic resistance patterns of the strain and their more frequent occurrence in hospital environments indicated plasmid-mediated resistance. R-plasmid transfer, minimum inhibition concentration and resistance elimination were studied in representative strains. The resistant S. london strain and transconjugants of Escherichia coli rendered resistant were compared. The results proved that multiple resistance was plasmid-mediated.

Childhood Maltreatment and PTSD: Spiritual Well-Being and Intimate Partner Violence as Mediators

PubMed Central

Zhang, Huaiyu; Pittman, Delishia M.; Lamis, Dorian A.; Fischer, Nicole L.; Schwenke, Tomina J.; Carr, Erika R.; Shah, Sanjay; Kaslow, Nadine J.

2016-01-01

Childhood maltreatment places individuals, including African American women who are undereducated and economically disadvantaged, at risk for developing posttraumatic stress disorder (PTSD) symptoms. Participants were 192 African American women with a history in the prior year of both a suicide attempt and intimate partner violence (IPV) exposure. They were recruited from a public hospital that provides medical and mental health treatment to mostly low-income patients. A simple mediator model was used to examine if (1) existential well-being (sense of purpose) and/or religious well-being (relationship with God) mediated the link between childhood maltreatment and adult PTSD symptoms. Sequential multiple mediator models determined if physical and nonphysical IPV enhanced our understanding of the mediational association among the aforementioned variables. Findings suggest that existential well-being mediated the association between childhood maltreatment and adult PTSD symptoms in a simple mediator model, and existential well-being and recent nonphysical IPV served as sequential multiple mediators of this link. However, religious well-being and physical IPV were not significant mediators. Findings underscore the importance of enhancing existential well-being in the treatment of suicidal African American women with a history of childhood maltreatment and IPV. PMID:26989343

Identification of suitable genes contributes to lung adenocarcinoma clustering by multiple meta-analysis methods.

PubMed

Yang, Ze-Hui; Zheng, Rui; Gao, Yuan; Zhang, Qiang

2016-09-01

With the widespread application of high-throughput technology, numerous meta-analysis methods have been proposed for differential expression profiling across multiple studies. We identified the suitable differentially expressed (DE) genes that contributed to lung adenocarcinoma (ADC) clustering based on seven popular multiple meta-analysis methods. Seven microarray expression profiles of ADC and normal controls were extracted from the ArrayExpress database. The Bioconductor was used to perform the data preliminary preprocessing. Then, DE genes across multiple studies were identified. Hierarchical clustering was applied to compare the classification performance for microarray data samples. The classification efficiency was compared based on accuracy, sensitivity and specificity. Across seven datasets, 573 ADC cases and 222 normal controls were collected. After filtering out unexpressed and noninformative genes, 3688 genes were remained for further analysis. The classification efficiency analysis showed that DE genes identified by sum of ranks method separated ADC from normal controls with the best accuracy, sensitivity and specificity of 0.953, 0.969 and 0.932, respectively. The gene set with the highest classification accuracy mainly participated in the regulation of response to external stimulus (P = 7.97E-04), cyclic nucleotide-mediated signaling (P = 0.01), regulation of cell morphogenesis (P = 0.01) and regulation of cell proliferation (P = 0.01). Evaluation of DE genes identified by different meta-analysis methods in classification efficiency provided a new perspective to the choice of the suitable method in a given application. Varying meta-analysis methods always present varying abilities, so synthetic consideration should be taken when providing meta-analysis methods for particular research. © 2015 John Wiley & Sons Ltd.

Balancing competing needs mediates the association of caregiving demand with caregiver role strain and depressive symptoms of dementia caregivers: A cross-sectional study.

PubMed

Liu, Hsin-Yun; Yang, Ching-Tzu; Wang, Yu-Nu; Hsu, Wen-Chuin; Huang, Tzu-Hsin; Lin, Yueh-E; Liu, Chin-Yi; Shyu, Yea-Ing L

2017-12-01

To examine the role of balancing competing needs in the relationship between caregiving demand and caregiving outcomes (caregivers' role strain and depressive symptoms). Caregivers who do not balance competing needs are more likely to experience negative caregiving outcomes, suggesting that balance mediates between caregiving demand and caregiving outcomes. Identifying a mediator of negative caregiving effects may help in developing tailored interventions for family caregivers of persons with dementia. A cross-sectional, correlational design. Data were collected from family caregivers' self-completed questionnaires between March 2013 - April 2014. A convenience sample of 120 family caregivers and care receivers with dementia was enrolled. We examined whether balance mediated the relationship between caregiving demand and caregiving outcomes (caregivers' role strain and depressive symptoms) by multiple regression analysis. To evaluate the significance of the indirect effect of caregiver balance, we used the Sobel test and Monte Carlo method, an alternative approach to testing mediation. Balancing competing needs completely mediated the association of caregiving demand with depressive symptoms and partially mediated the association of caregiving demand with role strain. Assessing caregivers' self-perceived sense of balance may help to identify caregivers at high risk for role strain and depressive symptoms. Interventions to enhance caregivers' perceived sense of balance between competing needs may provide a strategy for reducing the negative effects of caregiving. © 2017 John Wiley & Sons Ltd.

Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus.

PubMed

Sonoda, Mika; Shoji, Tetsuo; Kuwamura, Yukinobu; Okute, Yujiro; Naganuma, Toshihide; Shima, Hideaki; Motoyama, Koka; Morioka, Tomoaki; Mori, Katsuhito; Fukumoto, Shinya; Shioi, Atsushi; Shimono, Taro; Fujii, Hisako; Kabata, Daijiro; Shintani, Ayumi; Emoto, Masanori; Inaba, Masaaki

2017-06-29

Cognitive impairment is more prevalent in those with decreased kidney function. We tested a hypothesis that an increased homocysteine and/or cerebral small vessel diseases (SVDs) mediate the link between kidney and cognitive functions in a cross-sectional study in 143 type 2 diabetes patients without diagnosis of dementia or prior stroke. The exposure and outcome variables were estimated glomerular filtration rate (eGFR) and cognitive performance evaluated with Modified Mini-Mental State (3 MS) examination, respectively. The candidate mediators were plasma homocysteine concentration, and SVDs including silent cerebral infarction, cerebral microbleed, periventricular hyperintensity, and deep and subcortical white matter hyperintensity by magnetic resonance imaging. In multiple regression models adjusted for 12 potential confounders, eGFR was positively associated with 3 MS score, inversely with homocysteine, but not significantly with the presence of any type of SVD. The association of eGFR with 3 MS remained significant when each of the SVDs was added to the model, whereas it disappeared when homocysteine was included in place of SVD. Mediation analysis indicated nearly significant mediation of homocysteine (P = 0.062) but no meaningful mediations of SVDs (P = 0.842-0.930). Thus, homocysteine, not SVDs, was shown to be the possible mediator between kidney and cognitive functions in patients with type 2 diabetes mellitus.

Examining mediators of child sexual abuse and sexually transmitted infections.

PubMed

Sutherland, Melissa A

2011-01-01

Interpersonal violence has increasingly been identified as a risk factor for sexually transmitted infections. Understanding the pathways between violence and sexually transmitted infections is essential to designing effective interventions. The aim of this study was to examine dissociative symptoms, alcohol use, and intimate partner physical violence and sexual coercion as mediators of child sexual abuse and lifetime sexually transmitted infection diagnosis among a sample of women. A convenience sample of 202 women was recruited from healthcare settings, with 189 complete cases for analysis. A multiple mediation model tested the proposed mediators of child sexual abuse and lifetime sexually transmitted infection diagnosis. Bootstrapping, a resampling method, was used to test for mediation. Key variables included child sexual abuse, dissociative symptoms, alcohol use, and intimate partner violence. Child sexual abuse was reported by 46% of the study participants (n = 93). Child sexual abuse was found to have an indirect effect on lifetime sexually transmitted infection diagnosis, with the effect occurring through dissociative symptoms (95% confidence interval = 0.0033-0.4714) and sexual coercion (95% confidence interval = 0.0359-0.7694). Alcohol use and physical violence were not found to be significant mediators. This study suggests that dissociation and intimate partner sexual coercion are important mediators of child sexual abuse and sexually transmitted infection diagnosis. Therefore, interventions that consider the roles of dissociative symptoms and interpersonal violence may be effective in preventing sexually transmitted infections among women.

Multiple Mediation of Self-Esteem and Perceived Social Support in the Relationship between Loneliness and Life Satisfaction

ERIC Educational Resources Information Center

Yildiz, Mehmet Ali

2017-01-01

The purpose of this study is to test serial-multiple mediation role of self-esteem and perceived social support on the relationship between university students' loneliness and life satisfaction. The participants of this study consisted of 398 undergraduate students, with 289 females and 109 males aged between 17 and 41 with a mean age of 21.79 (SD…

Suicidal ideation among suburban adolescents: The influence of school bullying and other mediating risk factors.

PubMed

Lardier, David T; Barrios, Veronica R; Garcia-Reid, Pauline; Reid, Robert J

2016-10-01

Prior research has identified multiple factors that influence suicidal ideation (SI) among bullied youth. The effects of school bullying on SI cannot be considered in isolation. In this study, we examined the influence of school bullying on SI, through a constellation of risks, which include depressive and anxiety symptoms, family conflict, and alcohol, tobacco, and other drug (ATOD) use. We also provide recommendations for therapists working with bullied youth. Our sample consisted of 488 adolescents (ages 10-18 years) from a northern New Jersey, United States suburban community. Students were recruited through the district's physical education and health classes. Students responded to multiple measures, which included family cohesion/conflict, ATOD use, mental health indicators, SI, and school bullying experiences. Following preliminary analyses, several logistic regression models were used to assess the direct influence of bullying on SI, as well as the unique effects of family conflict, depressive and anxiety symptoms, and substance use. In addition, a parallel multiple mediating model with the PROCESS macro in SPSS was used to further assess mediating effects. Logistic regression results indicated that school bullying increased the odds of SI among males and females and that when mediating variables were added to the model, bullying no longer had a significant influence on SI. Overall, these results display that for both males and females, school bullying was a significant contributor to SI. Results from the parallel multiple mediating model further illustrated the mediating effects that family conflict, depression, and ATOD use had between bullying and SI. Some variation was noted based on gender. This study draws attention to the multiple experiences associated with school bullying on SI, and how these results may differ by gender. The results of this study are particularly important for those working directly and indirectly with bullied youth. Therapists that engage bullied youth need to consider the multiple spheres of influence that may increase SI among male and female clients. To holistically and adequately assess SI among bullied youth, therapists must also consider how these mechanisms vary between gender groups.

Motivation and exercise dependence: a study based on self-determination theory.

PubMed

González-Cutre, David; Sicilia, Alvaro

2012-06-01

The objective of this study was to use self-determination theory to analyze the relationships of several motivational variables with exercise dependence. The study involved 531 exercisers, ranging in age from 16 to 60 years old, who responded to differentquestionnaires assessing perception of motivational climate, satisfaction of basic psychological needs, motivation types, and exercise dependence. The results of multiple mediation analysis revealed that ego-involving climate and perceived competence positively predicted exercise dependence in a directed and mediated manner through introjected and external regulation. Gender and age did not moderate the analyzed relationships. These results allow us to better understand the motivational process explaining exercise dependence, demonstrating the negative influence of the ego-involving climate in the context of exercise.

Homeologous plastid DNA transformation in tobacco is mediated by multiple recombination events.

PubMed Central

Kavanagh, T A; Thanh, N D; Lao, N T; McGrath, N; Peter, S O; Horváth, E M; Dix, P J; Medgyesy, P

1999-01-01

Efficient plastid transformation has been achieved in Nicotiana tabacum using cloned plastid DNA of Solanum nigrum carrying mutations conferring spectinomycin and streptomycin resistance. The use of the incompletely homologous (homeologous) Solanum plastid DNA as donor resulted in a Nicotiana plastid transformation frequency comparable with that of other experiments where completely homologous plastid DNA was introduced. Physical mapping and nucleotide sequence analysis of the targeted plastid DNA region in the transformants demonstrated efficient site-specific integration of the 7.8-kb Solanum plastid DNA and the exclusion of the vector DNA. The integration of the cloned Solanum plastid DNA into the Nicotiana plastid genome involved multiple recombination events as revealed by the presence of discontinuous tracts of Solanum-specific sequences that were interspersed between Nicotiana-specific markers. Marked position effects resulted in very frequent cointegration of the nonselected peripheral donor markers located adjacent to the vector DNA. Data presented here on the efficiency and features of homeologous plastid DNA recombination are consistent with the existence of an active RecA-mediated, but a diminished mismatch, recombination/repair system in higher-plant plastids. PMID:10388829

Cannabis use expectancies mediate the relation between depressive symptoms and cannabis use among cannabis-dependent veterans.

PubMed

Farris, Samantha G; Zvolensky, Michael J; Boden, Matthew Tyler; Bonn-Miller, Marcel O

2014-01-01

The current study examined the cross-sectional associations between depressive symptoms and cannabis use, and the mediating role of positive and negative expectancies of cannabis use. Participants (n = 100) were cannabis-dependent veterans recruited as part of a larger self-guided cannabis quit study. Baseline (prequit) data were used. Depressive symptoms were assessed using the General Depression subscale of the Inventory of Depression and Anxiety Symptoms (IDAS), and cannabis use expectancies were assessed using the Marijuana Effect Expectancies Questionnaire. Quantity of cannabis use in the past 90 days was assessed with the Timeline Follow-Back. A parallel multiple mediation path analysis was conducted to simultaneously examine the effects of positive and negative expectancies as mediators of the relation between IDAS-Depression and prequit cannabis use. Results indicated that depressive symptoms were indirectly related to cannabis use through positive, but not negative, expectancies. This effect was unique to IDAS-Dysphoria symptoms. Depressive symptoms, particularly cognitive-affective symptom features, may be important to consider in better understanding positive cannabis effect expectancies among veterans in regard to cannabis use.

The relationship between Internet addiction and bulimia in a sample of Chinese college students: depression as partial mediator between Internet addiction and bulimia.

PubMed

Tao, ZhuoLi

2013-09-01

It has been reported that Internet addiction is associated with substance dependence. Eating disorders have high rates of co-morbidity with substance use disorders. The relationship between Internet addiction and eating disorders was reported in a previous study. To examine the hypothesis that Internet addiction is closely associated with bulimia. The hypothesis that depression mediates the relationship between Internet addiction and bulimia symptoms was also tested. 2,036 Chinese college students were assessed on Internet addiction, eating behaviors and depression. Binge eating, compensatory behaviors, weight concern, menarche and weight change were also reported. Multiple regression analysis was used to test the mediating effect of depression. Internet addicts showed significantly higher scores on most subscales on EDI-1 than the controls. They reported significantly more binge eating, weight concern and weight change than the controls. Among all of the participants, depression was found to be a partial mediator in the relationship between Internet addiction and bulimia. This survey provides evidence of the co-morbidity of Internet addiction and bulimia.

Emotional maltreatment and disordered eating in adolescents: testing the mediating role of emotion regulation.

PubMed

Mills, Pamela; Newman, Emily Frances; Cossar, Jill; Murray, George

2015-01-01

The present study aimed to determine if emotion regulation mediates the relationship between emotional maltreatment and disordered eating behavior in adolescents. Participants were 222 secondary school pupils (aged 14-18 years) from a state high school in the UK. Standardized questionnaire measures were used to gather self-report data on emotional abuse and emotional neglect, functional and dysfunctional emotion regulation strategies and disordered eating behavior. Results showed that disordered eating was associated with emotional abuse, dysfunctional emotion regulation and being female. Multiple mediation analysis found an indirect relationship between emotional abuse and disordered eating through dysfunctional emotion regulation. Interestingly, emotional neglect predicted lower levels of functional emotion regulation. The findings support previous research showing emotion regulation to mediate the relationship between childhood abuse and disordered eating in adults and a differential effect of abuse and neglect on emotion regulation. Longitudinal studies are required to confirm the direction of relationships; however these data suggest that dysfunctional emotion regulation is a significant variable in the development of disordered eating and may be a useful target for intervention. Copyright © 2014. Published by Elsevier Ltd.

Mental well-being mediates the relationship between perceived stress and perceived health.

PubMed

Teh, Hui Chian; Archer, Josephine A; Chang, Weining; Chen, S H Annabel

2015-02-01

The association between stress and health has been well researched in the past; however, comparatively few mediators have been tested to understand the underlying mechanism. With increasing awareness on mental well-being, this study evaluated the relationship between perceived stress and perceived health and examined mental well-being as a mediator. Two-hundred undergraduates aged 21 to 26 years completed the English Perceived Stress Scale, Health Status Questionnaire and Asian Mental Well-Being Scale that assess perceived stress, perceived health and mental well-being, respectively. Factor analysis and structural equation modelling on the Perceived Stress Scale replicated the reported two-factor structure after excluding an insignificant item. Linear multiple regression analyses indicated that perceived stress was negatively associated with perceived health. Results showed that mental well-being partially mediated the relationship between perceived stress and perceived health, although it is acknowledged that this association could be bidirectional. Findings from the present study suggest that future research could focus on reducing stress and improving mental well-being to alleviate the effect of stress on health. © 2013 John Wiley & Sons, Ltd.

Social pathways to health: On the mediating role of the social network in the relation between socio-economic position and health.

PubMed

Aartsen, Marja; Veenstra, Marijke; Hansen, Thomas

2017-12-01

Good health is one of the key qualities of life, but opportunities to be and remain healthy are unequally distributed across socio-economic groups. The beneficial health effects of the social network are well known. However, research on the social network as potential mediator in the pathway from socio-economic position (SEP) to health is scarce, while there are good reasons to expect a socio-economical patterning of networks. We aim to contribute to our understanding of socio-economic inequalities in health by examining the mediating role of structural and functional characteristics of the social network in the SEP-health relationship. Data were from the second wave of the Norwegian study on the life course, aging and generation study (NorLAG) and comprised 4534 men and 4690 women aged between 40 and 81. We applied multiple mediation models to evaluate the relative importance of each network characteristic, and multiple group analysis to examine differences between middle-aged and older men and women. Our results indicated a clear socio-economical patterning of the social network for men and women. People with higher SEP had social networks that better protect against loneliness, which in turn lead to better health outcomes. The explained variance in health in older people by the social network and SEP was only half of the explained variance observed in middle-aged people, suggesting that other factors than SEP were more important for health when people age. We conclude that it is the function of the network, rather than the structure, that counts for health.

Genetic insights into the mechanisms of Fgf signaling

PubMed Central

Brewer, J. Richard; Mazot, Pierre; Soriano, Philippe

2016-01-01

The fibroblast growth factor (Fgf) family of ligands and receptor tyrosine kinases is required throughout embryonic and postnatal development and also regulates multiple homeostatic functions in the adult. Aberrant Fgf signaling causes many congenital disorders and underlies multiple forms of cancer. Understanding the mechanisms that govern Fgf signaling is therefore important to appreciate many aspects of Fgf biology and disease. Here we review the mechanisms of Fgf signaling by focusing on genetic strategies that enable in vivo analysis. These studies support an important role for Erk1/2 as a mediator of Fgf signaling in many biological processes but have also provided strong evidence for additional signaling pathways in transmitting Fgf signaling in vivo. PMID:27036966

Isoflurane Impairs Low-Frequency Feedback but Leaves High-Frequency Feedforward Connectivity Intact in the Fly Brain.

PubMed

Cohen, Dror; van Swinderen, Bruno; Tsuchiya, Naotsugu

2018-01-01

Hierarchically organized brains communicate through feedforward (FF) and feedback (FB) pathways. In mammals, FF and FB are mediated by higher and lower frequencies during wakefulness. FB is preferentially impaired by general anesthetics in multiple mammalian species. This suggests FB serves critical functions in waking brains. The brain of Drosophila melanogaster (fruit fly) is also hierarchically organized, but the presence of FB in these brains is not established. Here, we studied FB in the fly brain, by simultaneously recording local field potentials (LFPs) from low-order peripheral structures and higher-order central structures. We analyzed the data using Granger causality (GC), the first application of this analysis technique to recordings from the insect brain. Our analysis revealed that low frequencies (0.1-5 Hz) mediated FB from the center to the periphery, while higher frequencies (10-45 Hz) mediated FF in the opposite direction. Further, isoflurane anesthesia preferentially reduced FB. Our results imply that the spectral characteristics of FF and FB may be a signature of hierarchically organized brains that is conserved from insects to mammals. We speculate that general anesthetics may induce unresponsiveness across species by targeting the mechanisms that support FB.

Isoflurane Impairs Low-Frequency Feedback but Leaves High-Frequency Feedforward Connectivity Intact in the Fly Brain

PubMed Central

2018-01-01

Abstract Hierarchically organized brains communicate through feedforward (FF) and feedback (FB) pathways. In mammals, FF and FB are mediated by higher and lower frequencies during wakefulness. FB is preferentially impaired by general anesthetics in multiple mammalian species. This suggests FB serves critical functions in waking brains. The brain of Drosophila melanogaster (fruit fly) is also hierarchically organized, but the presence of FB in these brains is not established. Here, we studied FB in the fly brain, by simultaneously recording local field potentials (LFPs) from low-order peripheral structures and higher-order central structures. We analyzed the data using Granger causality (GC), the first application of this analysis technique to recordings from the insect brain. Our analysis revealed that low frequencies (0.1–5 Hz) mediated FB from the center to the periphery, while higher frequencies (10–45 Hz) mediated FF in the opposite direction. Further, isoflurane anesthesia preferentially reduced FB. Our results imply that the spectral characteristics of FF and FB may be a signature of hierarchically organized brains that is conserved from insects to mammals. We speculate that general anesthetics may induce unresponsiveness across species by targeting the mechanisms that support FB. PMID:29541686

Bullying and HIV Risk Among High School Teenagers: The Mediating Role of Teen Dating Violence.

PubMed

Okumu, Moses; Mengo, Cecilia; Ombayo, Bernadette; Small, Eusebius

2017-10-01

Teen dating violence (TDV), bullying, and HIV risk behaviors are public health concerns that impact adolescents in the United States. National estimates reveal high rates of these risk behaviors among high school students. Based on theoretical and empirical evidence, we hypothesized that experiencing teen dating violence (sexual and physical) would mediate the impact of bullying on HIV risk. Data were from the 2013 National Youth Behavior Risk Surveillance Survey (YRBSS) among students who answered questions on bullying, TDV, and HIV risk (N = 13,571). The YRBSS is conducted biennially among 9th- to 12th-grade students nationally. We used multiple regression analysis and Hayes' SPSS process macro to examine the 2 study hypotheses. Findings from bivariate analysis suggest an association between bullying and HIV risk. The study also found associations between physical, sexual teen dating violence and HIV risk. Results also indicate that both physical and sexual teen dating violence mediate the association between bullying and HIV risk. Our findings suggest that multidimensional interventions should be developed to reduce the rate of teen dating violence and combat bullying as a preventative method for HIV risk among high school students. © 2017, American School Health Association.

A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex.

PubMed

Armour, Sean M; Bennett, Eric J; Braun, Craig R; Zhang, Xiao-Yong; McMahon, Steven B; Gygi, Steven P; Harper, J Wade; Sinclair, David A

2013-04-01

Although many functions and targets have been attributed to the histone and protein deacetylase SIRT1, a comprehensive analysis of SIRT1 binding proteins yielding a high-confidence interaction map has not been established. Using a comparative statistical analysis of binding partners, we have assembled a high-confidence SIRT1 interactome. Employing this method, we identified the deubiquitinating enzyme ubiquitin-specific protease 22 (USP22), a component of the deubiquitinating module (DUBm) of the SAGA transcriptional coactivating complex, as a SIRT1-interacting partner. We found that this interaction is highly specific, requires the ZnF-UBP domain of USP22, and is disrupted by the inactivating H363Y mutation within SIRT1. Moreover, we show that USP22 is acetylated on multiple lysine residues and that alteration of a single lysine (K129) within the ZnF-UBP domain is sufficient to alter interaction of the DUBm with the core SAGA complex. Furthermore, USP22-mediated recruitment of SIRT1 activity promotes the deacetylation of individual SAGA complex components. Our results indicate an important role of SIRT1-mediated deacetylation in regulating the formation of DUBm subcomplexes within the larger SAGA complex.

Anxiety and depression mediate the health-related quality of life differently in patients with cardiovascular disease and stroke-preliminary report of the Yilan study: a population-based community health survey.

PubMed

Hsu, Nai-Wei; Tsao, Hsuan-Ming; Chen, Hsi-Chung; Chou, Pesus

2014-01-01

Cardiovascular disease and stroke have emerged as substantial and growing health challenges to populations around the world. Besides for the survival and medical prognosis, how to improve the health-related quality of life (HRQoL) might also become one of the goals of treatment programs. There are multiple factors that influence HRQol, including comorbidity, mental function and lifestyle. However, substantial research and investigation have still not clarified these underlying pathways, which merit further attention. The purpose of this study was to determine how psychological factors affect the link between cardiovascular disease and stroke with HRQoL. A total of 1,285 elder subjects at least 65 years of age (47.2% male) were enrolled. The mental function and HRQol of each patient was then measured using the Hospital Anxiety and Depression Scale and Short Form-12. After multiple regression analysis, anxiety, depression, cardiovascular disease, stroke, education level and age were shown to be associated with both mental component score (MCS) and physical component score (PCS). In the mediation analysis using the SPSS macro provided by Preacher and Hayes, cardiovascular disease and stroke affected HRQoL via anxiety and depression, respectively. These results suggest that cardiovascular disease and stroke have negative impacts on patient MCS and PCS through different underlying pathways. Cardiovascular disease influences the HRQoL both directly and indirectly with the mediation of anxiety, and stroke influences the HRQoL by way of depression. These findings support the proposition that different combinations of both physical and psychological support are necessary to best manage these diseases.

Mediation of the relationship between callous-unemotional traits and proactive aggression by amygdala response to fear among children with conduct problems.

PubMed

Lozier, Leah M; Cardinale, Elise M; VanMeter, John W; Marsh, Abigail A

2014-06-01

Among youths with conduct problems, callous-unemotional (CU) traits are known to be an important determinant of symptom severity, prognosis, and treatment responsiveness. But positive correlations between conduct problems and CU traits result in suppressor effects that may mask important neurobiological distinctions among subgroups of children with conduct problems. To assess the unique neurobiological covariates of CU traits and externalizing behaviors in youths with conduct problems and determine whether neural dysfunction linked to CU traits mediates the link between callousness and proactive aggression. This cross-sectional case-control study involved behavioral testing and neuroimaging that were conducted at a university research institution. Neuroimaging was conducted using a 3-T Siemens magnetic resonance imaging scanner. It included 46 community-recruited male and female juveniles aged 10 to 17 years, including 16 healthy control participants and 30 youths with conduct problems with both low and high levels of CU traits. Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging during an implicit face-emotion processing task and analyzed using whole-brain and region of interest-based analysis of variance and multiple-regression analyses. Analysis of variance revealed no group differences in the amygdala. By contrast, consistent with the existence of suppressor effects, multiple-regression analysis found amygdala responses to fearful expressions to be negatively associated with CU traits (x = 26, y = 0, z = -12; k = 1) and positively associated with externalizing behavior (x = 24, y = 0, z = -14; k = 8) when both variables were modeled simultaneously. Reduced amygdala responses mediated the relationship between CU traits and proactive aggression. The results linked proactive aggression in youths with CU traits to hypoactive amygdala responses to emotional distress cues, consistent with theories that externalizing behaviors, particularly proactive aggression, in youths with these traits stem from deficient empathic responses to distress. Amygdala hypoactivity may represent an intermediate phenotype, offering new insights into effective treatment strategies for conduct problems.

Mediator-regulated transcription through the +1 nucleosome.

PubMed

Nock, Adam; Ascano, Janice M; Barrero, Maria J; Malik, Sohail

2012-12-28

Many genes are regulated at the level of a Pol II that is recruited to a nucleosome-free region upstream of the +1 nucleosome. How the Mediator coactivator complex, which functions at multiple steps, affects transcription through the promoter proximal region, including this nucleosome, remains largely unaddressed. We have established a fully defined in vitro assay system to delineate mechanisms for Pol II transit across the +1 nucleosome. Our results reveal cooperative functions of multiple cofactors, particularly of Mediator and elongation factor SII, in transcribing into this nucleosome. This is achieved, in part, through an unusual activity of SII that alters the intrinsic catalytic properties of promoter-proximal Pol II and, in concert with the Mediator, leads to enhancement in transcription of nucleosomal DNA. Our data provide additional mechanistic bases for Mediator function after recruitment of Pol II and, potentially, for regulation of genes controlled via nucleosome-mediated promoter-proximal pausing. Copyright © 2012 Elsevier Inc. All rights reserved.

Mediated moderation of the relation between maternal and adolescent depressive symptoms: role of adolescent physical health.

PubMed

Ferro, Mark A

2015-11-01

To examine the mediating effect of family functioning on the relation between maternal and adolescent depressive symptoms and determine whether the magnitude of the mediating effect is different for adolescents with and without chronic physical health conditions. Data come from the National Longitudinal Survey of Children and Youth. A representative survey of 11,813 adolescents and their mothers was included. Maternal and adolescent depressive symptoms were measured using the 12-item Center for Epidemiological Studies Depression Scale. Family functioning was measured using the McMaster Family Assessment Device. Multilevel multiple-group path analysis was used to examine potential mediating and moderating effects. Family functioning measured when adolescents were 14-15 years mediated the relation between maternal depressive symptoms (measured at 10-13 years) and adolescent depressive symptoms (measured at 16-19 years) for both adolescents with [αβ = 0.02 (0.02, 0.03)] and without chronic health conditions [αβ = 0.01 (0.00, 0.01)]. These findings provided evidence to suggest mediated moderation, Δαβ = 0.02 (0.01, 0.03), that is, the mediating effect of family functioning was significantly larger for adolescents with chronic health conditions. The mediating effect of family functioning in the relation between maternal and adolescent depressive symptoms is larger for adolescents with chronic health conditions. Within the framework of family-centered care, maternal depressive symptoms and family functioning are suitable targets for preventive intervention for adolescents with chronic health conditions.

Investigating elementary principals' science beliefs and knowledge and its relationship to students' science outcomes

NASA Astrophysics Data System (ADS)

Khan, Uzma Zafar

The aim of this quantitative study was to investigate elementary principals' beliefs about reformed science teaching and learning, science subject matter knowledge, and how these factors relate to fourth grade students' superior science outcomes. Online survey methodology was used for data collection and included a demographic questionnaire and two survey instruments: the K-4 Physical Science Misconceptions Oriented Science Assessment Resources for Teachers (MOSART) and the Beliefs About Reformed Science Teaching and Learning (BARSTL). Hierarchical multiple regression analysis was used to assess the separate and collective contributions of background variables such as principals' personal and school characteristics, principals' science teaching and learning beliefs, and principals' science knowledge on students' superior science outcomes. Mediation analysis was also used to explore whether principals' science knowledge mediated the relationship between their beliefs about science teaching and learning and students' science outcomes. Findings indicated that principals' science beliefs and knowledge do not contribute to predicting students' superior science scores. Fifty-two percent of the variance in percentage of students with superior science scores was explained by school characteristics with free or reduced price lunch and school type as the only significant individual predictors. Furthermore, principals' science knowledge did not mediate the relationship between their science beliefs and students' science outcomes. There was no statistically significant variation among the variables. The data failed to support the proposed mediation model of the study. Implications for future research are discussed.

Adverse childhood experiences and health anxiety in adulthood.

PubMed

Reiser, Sarah J; McMillan, Katherine A; Wright, Kristi D; Asmundson, Gordon J G

2014-03-01

Childhood experiences are thought to predispose a person to the development of health anxiety later in life. However, there is a lack of research investigating the influence of specific adverse experiences (e.g., childhood abuse, household dysfunction) on this condition. The current study examined the cumulative influence of multiple types of childhood adversities on health anxiety in adulthood. Adults 18-59 years of age (N=264) completed a battery of measures to assess adverse childhood experiences, health anxiety, and associated constructs (i.e., negative affect and trait anxiety). Significant associations were observed between adverse childhood experiences, health anxiety, and associated constructs. Hierarchical multiple regression analysis indicted that adverse childhood experiences were predictive of health anxiety in adulthood; however, the unique contribution of these experience were no longer significant following the inclusion of the other variables of interest. Subsequently, mediation analyses indicated that both negative affect and trait anxiety independently mediated the relationship between adverse childhood experiences and health anxiety in adulthood. Increased exposure to adverse childhood experiences is associated with higher levels of health anxiety in adulthood; this relationship is mediated through negative affect and trait anxiety. Findings support the long-term negative impact of cumulative adverse childhood experiences and emphasize the importance of addressing negative affect and trait anxiety in efforts to prevent and treat health anxiety. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cumulative Risk Exposure and Waist Circumference in Preschool-Aged Children: the Mediating Role of Television and Moderating Role of Sex.

PubMed

Grummon, Anna H; Vaughn, Amber; Jones, Deborah J; Ward, Dianne S

2017-08-01

Children exposed to multiple stressors are more likely to be overweight, but little is known about the mechanisms explaining this association. This cross-sectional study examined whether children exposed to multiple stressors had higher waist circumference, and whether this association was mediated through children's television time. Participants were 319 parent-child dyads. Children were 2-5 years old and had at least one overweight parent (BMI ≥ 25 kg/m 2 ). Data were collected at baseline of a larger childhood obesity prevention study and included information on psychosocial stressors (e.g., parenting stress), demographic stressors (e.g., low income), children's television time, and children's waist circumference. Two cumulative risk scores were created by summing stressors in each domain (demographic and psychosocial). Mediation and moderated mediation analyses were conducted. Indirect effects of both cumulative risk scores on waist circumference through television time were not significant; however, moderated mediation analyses found significant moderation by gender. The indirect effects of both risk scores on waist circumference through television time were significant and positive for girls, but near-zero for boys. Reducing television time should be explored as a strategy for buffering against the negative health effects of exposure to multiple stressors among girls. Longitudinal and intervention research is needed to confirm these results and to identify mediating factors between cumulative risk and body weight among boys.

Mediating Variables in a Transtheoretical Model Dietary Intervention Program

ERIC Educational Resources Information Center

Di Noia, Jennifer; Prochaska, James O.

2010-01-01

This study identified mediators of a Transtheoretical Model (TTM) intervention to increase fruit and vegetable consumption among economically disadvantaged African American adolescents (N = 549). Single-and multiple-mediator models were used to determine whether pros, cons, self-efficacy, and stages of change satisfied four conclusions necessary…

Peer substance use as a mediator between early pubertal timing and adolescent substance use: longitudinal associations and moderating effect of maltreatment.

PubMed

Negriff, Sonya; Trickett, Penelope K

2012-11-01

Early pubertal timing has received considerable empirical support as a risk for adolescent substance use. However, few studies have examined the mediators linking these variables. Therefore, the aims of this study were (1) to examine peer substance use as a mediator between pubertal timing and adolescent substance use longitudinally and (2) to test gender and maltreatment experience as moderators of the mediational model. Data were obtained from time 1, 2, and 3 of a longitudinal study of maltreatment and development. At time 1 the sample was comprised of 303 maltreated and 151 comparison children aged 9-13 years (213 females and 241 males). Longitudinal mediation was tested using structural equation modeling and moderating effects were tested using multiple group analysis. Peer substance use mediated the relationship between early pubertal timing and later adolescent substance use for the total sample. Moderation analyses indicated this significant indirect effect did not differ for males and females. However, it did differ for maltreated versus comparison adolescents with the mediational effect only remaining significant for the comparison group. This is one of the first studies to examine peer substance use as a mediator of pubertal timing and adolescent substance use using a longitudinal design. Early maturing males are at equal risk to early maturing females for interacting with peers that may draw them into substance use. Additionally, the findings indicate that while peers are mediators for comparison adolescents a different mechanism may link early puberty to substance use for maltreated adolescents. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Five-Factor Personality Traits and Subjective Health Among Caregivers: The Role of Caregiver Strain and Self-Efficacy

PubMed Central

Löckenhoff, Corinna E.; Duberstein, Paul R.; Friedman, Bruce; Costa, Paul T.

2011-01-01

This study examined the association among caregivers’ five-factor personality traits and subjective health with particular emphasis on the role of two theoretically implicated mediators: multi-domain self-efficacy and caregiver strain. The sample comprised 536 informal caregivers (mean age = 62.9 years, SD = 19.9, 72% female, 98% White) of community-dwelling older adults with multiple functional impairments. Both physical health and mental health were negatively associated with neuroticism and positively associated with extraversion and conscientiousness. Agreeableness and openness were associated with better subjective mental health and physical health, respectively. Multiple mediation analyses indicated that self-efficacy mediated all observed associations between personality and subjective health, whereas caregiver strain selectively mediated the associations of neuroticism and agreeableness with mental health. PMID:21417534

Altered intestinal epithelium-associated lymphocyte repertoires and function in ApcMin/+ mice.

PubMed

Marsh, Lorraine; Coletta, P Louise; Hull, Mark A; Selby, Peter J; Carding, Simon R

2012-01-01

ApcMin/+ mice spontaneously develop multiple intestinal adenomas along the length of the small intestine and colon. Currently little is known about the role of the immune system in regulating intestinal tumorigenesis in these animals. This study characterised small intestinal intraepithelial lympho-- cyte (IEL) populations in C56BL/6J ApcMin/+ mice and wild-type (Apc+/+) mice. We also determined the effect that T cells expressing either γδ or αβ encoded T cell receptors (TcR) exert on intestinal tumorigenesis. ApcMin/+ mice had significantly lower numbers of CD3+ IELs compared with Apc+/+ littermates and displayed reduced cytotoxicity against tumour target cells. Further analysis of IEL cytotoxicity revealed differences in the cytotoxic pathways utilised by IELs in ApcMin/+ and Apc+/+ mice with ApcMin/+ IELs displaying an absence of perforin/granzyme-mediated killing and increased levels of Fas-FasL-mediated cytotoxicity compared with wild-type IELs. Analysis of ApcMin/+ mice crossed with αβ T-cell deficient (TcRβ-/-) or γδ T-cell deficient (TcRδ-/-) mice on the same genetic background revealed decreased tumour multiplicity in the absence of both αβ and γδ T-cells. This study demonstrates that altered T-cell subsets play important roles in promoting tumorigenesis in ApcMin/+ mice and forms the basis for future mechanistic studies.

Principal component analysis of the cytokine and chemokine response to human traumatic brain injury.

PubMed

Helmy, Adel; Antoniades, Chrystalina A; Guilfoyle, Mathew R; Carpenter, Keri L H; Hutchinson, Peter J

2012-01-01

There is a growing realisation that neuro-inflammation plays a fundamental role in the pathology of Traumatic Brain Injury (TBI). This has led to the search for biomarkers that reflect these underlying inflammatory processes using techniques such as cerebral microdialysis. The interpretation of such biomarker data has been limited by the statistical methods used. When analysing data of this sort the multiple putative interactions between mediators need to be considered as well as the timing of production and high degree of statistical co-variance in levels of these mediators. Here we present a cytokine and chemokine dataset from human brain following human traumatic brain injury and use principal component analysis and partial least squares discriminant analysis to demonstrate the pattern of production following TBI, distinct phases of the humoral inflammatory response and the differing patterns of response in brain and in peripheral blood. This technique has the added advantage of making no assumptions about the Relative Recovery (RR) of microdialysis derived parameters. Taken together these techniques can be used in complex microdialysis datasets to summarise the data succinctly and generate hypotheses for future study.

Development of transgenic watermelon resistant to Cucumber mosaic virus and Watermelon mosaic virus by using a single chimeric transgene construct.

PubMed

Lin, Ching-Yi; Ku, Hsin-Mei; Chiang, Yi-Hua; Ho, Hsiu-Yin; Yu, Tsong-Ann; Jan, Fuh-Jyh

2012-10-01

Watermelon, an important fruit crop worldwide, is prone to attack by several viruses that often results in destructive yield loss. To develop a transgenic watermelon resistant to multiple virus infection, a single chimeric transgene comprising a silencer DNA from the partial N gene of Watermelon silver mottle virus (WSMoV) fused to the partial coat protein (CP) gene sequences of Cucumber mosaic virus (CMV), Cucumber green mottle mosaic virus (CGMMV) and Watermelon mosaic virus (WMV) was constructed and transformed into watermelon (cv. Feeling) via Agrobacterium-mediated transformation. Single or multiple transgene copies randomly inserted into various locations in the genome were confirmed by Southern blot analysis. Transgenic watermelon R(0) plants were individually challenged with CMV, CGMMV or WMV, or with a mixture of these three viruses for resistance evaluation. Two lines were identified to exhibit resistance to CMV, CGMMV, WMV individually, and a mixed inoculation of the three viruses. The R(1) progeny of the two resistant R(0) lines showed resistance to CMV and WMV, but not to CGMMV. Low level accumulation of transgene transcripts in resistant plants and small interfering (si) RNAs specific to CMV and WMV were readily detected in the resistant R(1) plants by northern blot analysis, indicating that the resistance was established via RNA-mediated post-transcriptional gene silencing (PTGS). Loss of the CGMMV CP-transgene fragment in R1 progeny might be the reason for the failure to resistant CGMMV infection, as shown by the absence of a hybridization signal and no detectable siRNA specific to CGMMV in Southern and northern blot analyses. In summary, this study demonstrated that fusion of different viral CP gene fragments in transgenic watermelon contributed to multiple virus resistance via PTGS. The construct and resistant watermelon lines developed in this study could be used in a watermelon breeding program for resistance to multiple viruses.

Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor

PubMed Central

Anandhakumar, Jayamani; Moustafa, Yara W.; Chowdhary, Surabhi; Kainth, Amoldeep S.

2016-01-01

Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the “anchor away” (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. PMID:27185874

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo

PubMed Central

Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-01-01

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. PMID:26240385

Mess management in microbial ecology: Rhetorical processes of disciplinary integration

NASA Astrophysics Data System (ADS)

McCracken, Christopher W.

As interdisciplinary work becomes more common in the sciences, research into the rhetorical processes mediating disciplinary integration becomes more vital. This dissertation, which takes as its subject the integration of microbiology and ecology, combines a postplural approach to rhetoric of science research with Victor Turner's "social drama" analysis and a third-generation activity theory methodological framework to identify conceptual and practical conflicts in interdisciplinary work and describe how, through visual and verbal communication, scientists negotiate these conflicts. First, to understand the conflicting disciplinary principles that might impede integration, the author conducts a Turnerian analysis of a disciplinary conflict that took place in the 1960s and 70s, during which American ecologists and biologists debated whether they should participate in the International Biological Program (IBP). Participation in the IBP ultimately contributed to the emergence of ecology as a discipline distinct from biology, and Turnerian social drama analysis of the debate surrounding participation lays bare the conflicting principles separating biology and ecology. Second, to answer the question of how these conflicting principles are negotiated in practice, the author reports on a yearlong qualitative study of scientists working in a microbial ecology laboratory. Focusing specifically on two case studies from this fieldwork that illustrate the key concept of textually mediated disciplinary integration, the author's analysis demonstrates how scientific objects emerge in differently situated practices, and how these objects manage to cohere despite their multiplicity through textually mediated rhetorical processes of calibration and alignment.

Global gene expression profiles in brain regions reflecting abnormal neuronal and glial functions targeting myelin sheaths after 28-day exposure to cuprizone in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abe, Hajime

Both developmental and postpubertal cuprizone (CPZ) exposure impairs hippocampal neurogenesis in rats. We previously found that developmental CPZ exposure alters the expression of genes related to neurogenesis, myelination, and synaptic transmission in specific brain regions of offspring. Here, we examined neuronal and glial toxicity profiles in response to postpubertal CPZ exposure by using expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex, and cerebellar vermis of 5-week-old male rats exposed to 0, 120, and 600 mg/kg CPZ for 28 days. Genes showing transcript upregulation were subjected to immunohistochemical analysis. We found transcript expression alterations at 600 mg/kgmore » for genes related to synaptic transmission, Ache and Prima1, and cell cycle regulation, Tfap4 and Cdkn1a, in the dentate gyrus, which showed aberrant neurogenesis in the subgranular zone. This dose downregulated myelination-related genes in multiple brain regions, whereas KLOTHO{sup +} oligodendrocyte density was decreased only in the corpus callosum. The corpus callosum showed an increase in transcript levels for inflammatory response-related genes and in the number of CD68{sup +} microglia, MT{sup +} astrocytes, and TUNEL{sup +} apoptotic cells. These results suggest that postpubertal CPZ exposure targets synaptic transmission and cell cycle regulation to affect neurogenesis in the dentate gyrus. CPZ suppressed myelination in multiple brain regions and KLOTHO-mediated oligodendrocyte maturation only in the corpus callosum. The increased number of CD68{sup +} microglia, MT{sup +} astrocytes, and TUNEL{sup +} apoptotic cells in the corpus callosum may be involved in the induction of KLOTHO{sup +} oligodendrocyte death and be a protective mechanism against myelin damage following CPZ exposure. - Highlights: • Target gene expression profiles were examined in rats after 28-day CPZ exposure. • Multiple brain region-specific global gene expression profiling was performed. • CPZ affected synaptic function and cell cycling in the hippocampal dentate gyrus. • CPZ suppressed KLOTHO-mediated oligodendrocyte maturation in the corpus callosum. • CPZ increased metallothionein-mediated protective mechanism against myelin damage.« less

Mechanisms and mediation in survival analysis: towards an integrated analytical framework.

PubMed

Pratschke, Jonathan; Haase, Trutz; Comber, Harry; Sharp, Linda; de Camargo Cancela, Marianna; Johnson, Howard

2016-02-29

A wide-ranging debate has taken place in recent years on mediation analysis and causal modelling, raising profound theoretical, philosophical and methodological questions. The authors build on the results of these discussions to work towards an integrated approach to the analysis of research questions that situate survival outcomes in relation to complex causal pathways with multiple mediators. The background to this contribution is the increasingly urgent need for policy-relevant research on the nature of inequalities in health and healthcare. The authors begin by summarising debates on causal inference, mediated effects and statistical models, showing that these three strands of research have powerful synergies. They review a range of approaches which seek to extend existing survival models to obtain valid estimates of mediation effects. They then argue for an alternative strategy, which involves integrating survival outcomes within Structural Equation Models via the discrete-time survival model. This approach can provide an integrated framework for studying mediation effects in relation to survival outcomes, an issue of great relevance in applied health research. The authors provide an example of how these techniques can be used to explore whether the social class position of patients has a significant indirect effect on the hazard of death from colon cancer. The results suggest that the indirect effects of social class on survival are substantial and negative (-0.23 overall). In addition to the substantial direct effect of this variable (-0.60), its indirect effects account for more than one quarter of the total effect. The two main pathways for this indirect effect, via emergency admission (-0.12), on the one hand, and hospital caseload, on the other, (-0.10) are of similar size. The discrete-time survival model provides an attractive way of integrating time-to-event data within the field of Structural Equation Modelling. The authors demonstrate the efficacy of this approach in identifying complex causal pathways that mediate the effects of a socio-economic baseline covariate on the hazard of death from colon cancer. The results show that this approach has the potential to shed light on a class of research questions which is of particular relevance in health research.

Helminths as governors of immune-mediated inflammation.

PubMed

Elliott, David E; Summers, Robert W; Weinstock, Joel V

2007-04-01

Immune-mediated diseases (e.g. inflammatory bowel disease, asthma, multiple sclerosis and autoimmune diabetes) are increasing in prevalence and emerge as populations adopt meticulously hygienic lifestyles. This change in lifestyles precludes exposure to helminths (parasitic worms). Loss of natural helminth exposure removes a previously universal Th2 and regulatory immune biasing imparted by these organisms. Helminths protect animals from developing immune-mediated diseases (colitis, reactive airway disease, encephalitis and diabetes). Clinical trials show that exposure to helminths can reduce disease activity in patients with ulcerative colitis or Crohn's disease. This paper summarises work by multiple groups demonstrating that colonization with helminths alters immune reactivity and protects against disease from dysregulated inflammation.

Relationship between pain and post-traumatic stress symptoms in palliative care.

PubMed

Roth, Maya L; St Cyr, Kate; Harle, Ingrid; Katz, Joel D

2013-08-01

Previous research suggests that patients receiving palliative care may simultaneously experience poorly managed pain and post-traumatic stress disorder (PTSD)-related symptoms as a result of their deteriorating health. To: 1) examine predictors of PTSD-related symptoms in patients requiring palliative care; 2) assess whether anxiety, depression, pain catastrophizing, and pain anxiety mediate the relationship between pain interference and PTSD-related symptoms; and 3) evaluate the impact of these variables on pain interference and PTSD-related symptoms. One hundred patients receiving palliative care at one of two palliative care sites in London, ON, Canada, completed the PTSD Checklist-Civilian version (PCL-C), the Hospital Anxiety and Depression Scale (HADS), the Pain Catastrophizing Scale (PCS), the Brief Pain Inventory-Short Form (BPI-SF), and the Pain Anxiety Symptoms Scale-20 (PASS-20). Hierarchical multiple regressions were used to examine HADS-Anxiety, HADS-Depression, PCS and PASS-20 scores as predictors of PCL-C scores; and mediation analyses were used to test the effect of HADS-Anxiety, HADS-Depression, PCS, and PASS-20 on the relationship between BPI-SF interference and PCL-C. Mediators that significantly affected this relationship in the individual mediator models were entered into a multiple mediator model. Only pain anxiety and pain catastrophizing emerged as significant mediators of the relationship between pain interference and PTSD-related symptoms. After being entered in a multiple mediator model, pain anxiety emerged as the strongest mediator. The findings of the present study reveal that pain and PTSD-related symptoms are important concerns in palliative care, and that pain must be addressed to best meet the needs of this population. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Evidence of Multiple Mediating Pathways in Associations Between Constructs of Stigma and Self-Reported Suicide Attempts in a Cross-Sectional Study of Gay and Bisexual Men.

PubMed

Salway, Travis; Gesink, Dionne; Ibrahim, Selahadin; Ferlatte, Olivier; Rhodes, Anne E; Brennan, David J; Marchand, Rick; Trussler, Terry

2018-05-01

Gay and bisexual men (GBM) are more likely to attempt suicide than heterosexual men. This disparity is commonly interpreted using minority stress theory; however, specific pathways from antigay stigma to suicidal behavior are poorly understood. We aimed to estimate associations between multiple constructs of stigma and suicide attempts among adult GBM, and to measure the proportion of these associations mediated by distinct suicide risk factors, thus identifying proximal points of intervention. Data were drawn from a Canadian community-based survey of adult GBM. Structural equation modeling was used to compare associations between three latent constructs-enacted stigma (e.g., discrimination, harassment), anticipated prejudice (worry about encountering antigay/bisexual prejudice), and sexuality concealment-and self-reported suicide attempts (last 12 months). Coefficients were estimated for direct, indirect, and total pathways and evaluated based on magnitude and statistical significance. The proportion of associations mediated by depression, drug/alcohol use, and social isolation was calculated using indirect paths. Among 7872 respondents, 3.4% reported a suicide attempt in the past 12 months. The largest total association was observed for enacted stigma, and this association was partially mediated by depression and drug/alcohol use. The total association of anticipated prejudice was relatively smaller and mediated by depression and social isolation. Concealment had an inverse association with suicide attempts as mediated by depression but was also positively associated with suicide attempts when mediated through social isolation. Multiple constructs of antigay stigma were associated with suicide attempts; however, mediating pathways differed by construct, suggesting that a combination of strategies is required to prevent suicide in adult GBM.

A biomaterial screening approach reveals microenvironmental mechanisms of drug resistance.

PubMed

Schwartz, Alyssa D; Barney, Lauren E; Jansen, Lauren E; Nguyen, Thuy V; Hall, Christopher L; Meyer, Aaron S; Peyton, Shelly R

2017-12-11

Traditional drug screening methods lack features of the tumor microenvironment that contribute to resistance. Most studies examine cell response in a single biomaterial platform in depth, leaving a gap in understanding how extracellular signals such as stiffness, dimensionality, and cell-cell contacts act independently or are integrated within a cell to affect either drug sensitivity or resistance. This is critically important, as adaptive resistance is mediated, at least in part, by the extracellular matrix (ECM) of the tumor microenvironment. We developed an approach to screen drug responses in cells cultured on 2D and in 3D biomaterial environments to explore how key features of ECM mediate drug response. This approach uncovered that cells on 2D hydrogels and spheroids encapsulated in 3D hydrogels were less responsive to receptor tyrosine kinase (RTK)-targeting drugs sorafenib and lapatinib, but not cytotoxic drugs, compared to single cells in hydrogels and cells on plastic. We found that transcriptomic differences between these in vitro models and tumor xenografts did not reveal mechanisms of ECM-mediated resistance to sorafenib. However, a systems biology analysis of phospho-kinome data uncovered that variation in MEK phosphorylation was associated with RTK-targeted drug resistance. Using sorafenib as a model drug, we found that co-administration with a MEK inhibitor decreased ECM-mediated resistance in vitro and reduced in vivo tumor burden compared to sorafenib alone. In sum, we provide a novel strategy for identifying and overcoming ECM-mediated resistance mechanisms by performing drug screening, phospho-kinome analysis, and systems biology across multiple biomaterial environments.

Coping mediates the influence of personality on life satisfaction in patients with rheumatic diseases.

PubMed

Vollmann, Manja; Pukrop, Jörg; Salewski, Christel

2016-04-01

A rheumatic disease can severely impair a person's quality of life. The degree of impairment, however, is not closely related to objective indicators of disease severity. This study investigated the influence and the interplay of core psychological factors, i.e., personality and coping, on life satisfaction in patients with rheumatic diseases. Particularly, it was tested whether coping mediates the effects of personality on life satisfaction. In a cross-sectional design, 158 patients diagnosed with a rheumatic disease completed questionnaires assessing the Big 5 personality traits (BFI-10), several disease-related coping strategies (EFK) and life satisfaction (HSWBS). Data were analyzed using a complex multiple mediation analysis with the Big 5 personality traits as predictors, coping strategies as mediators and life satisfaction as outcome. All personality traits and seven of the nine coping strategies were associated with life satisfaction (rs > |0.16|, ps ≤ 0.05). The mediation analysis revealed that personality traits had no direct, but rather indirect effects on life satisfaction through coping. Neuroticism had a negative indirect effect on life satisfaction through less active problem solving and more depressive coping (indirect effects > -0.03, ps < 0.05). Extraversion, agreeableness, and conscientiousness had positive indirect effects on life satisfaction through more active problem solving, less depressive coping and/or a more active search for social support (indirect effects > 0.06, ps < 0.05). Personality and coping play a role in adjustment to rheumatic diseases. The interplay of these variables should be considered in psychological interventions for patients with rheumatic diseases.

Protoplast isolation, transient transformation of leaf mesophyll protoplasts and improved Agrobacterium-mediated leaf disc infiltration of Phaseolus vulgaris: tools for rapid gene expression analysis.

PubMed

Nanjareddy, Kalpana; Arthikala, Manoj-Kumar; Blanco, Lourdes; Arellano, Elizabeth S; Lara, Miguel

2016-06-24

Phaseolus vulgaris is one of the most extensively studied model legumes in the world. The P. vulgaris genome sequence is available; therefore, the need for an efficient and rapid transformation system is more imperative than ever. The functional characterization of P. vulgaris genes is impeded chiefly due to the non-amenable nature of Phaseolus sp. to stable genetic transformation. Transient transformation systems are convenient and versatile alternatives for rapid gene functional characterization studies. Hence, the present work focuses on standardizing methodologies for protoplast isolation from multiple tissues and transient transformation protocols for rapid gene expression analysis in the recalcitrant grain legume P. vulgaris. Herein, we provide methodologies for the high-throughput isolation of leaf mesophyll-, flower petal-, hypocotyl-, root- and nodule-derived protoplasts from P. vulgaris. The highly efficient polyethylene glycol-mannitol magnesium (PEG-MMG)-mediated transformation of leaf mesophyll protoplasts was optimized using a GUS reporter gene. We used the P. vulgaris SNF1-related protein kinase 1 (PvSnRK1) gene as proof of concept to demonstrate rapid gene functional analysis. An RT-qPCR analysis of protoplasts that had been transformed with PvSnRK1-RNAi and PvSnRK1-OE vectors showed the significant downregulation and ectopic constitutive expression (overexpression), respectively, of the PvSnRK1 transcript. We also demonstrated an improved transient transformation approach, sonication-assisted Agrobacterium-mediated transformation (SAAT), for the leaf disc infiltration of P. vulgaris. Interestingly, this method resulted in a 90 % transformation efficiency and transformed 60-85 % of the cells in a given area of the leaf surface. The constitutive expression of YFP further confirmed the amenability of the system to gene functional characterization studies. We present simple and efficient methodologies for protoplast isolation from multiple P. vulgaris tissues. We also provide a high-efficiency and amenable method for leaf mesophyll transformation for rapid gene functional characterization studies. Furthermore, a modified SAAT leaf disc infiltration approach aids in validating genes and their functions. Together, these methods help to rapidly unravel novel gene functions and are promising tools for P. vulgaris research.

CHRONOS: a time-varying method for microRNA-mediated subpathway enrichment analysis.

PubMed

Vrahatis, Aristidis G; Dimitrakopoulou, Konstantina; Balomenos, Panos; Tsakalidis, Athanasios K; Bezerianos, Anastasios

2016-03-15

In the era of network medicine and the rapid growth of paired time series mRNA/microRNA expression experiments, there is an urgent need for pathway enrichment analysis methods able to capture the time- and condition-specific 'active parts' of the biological circuitry as well as the microRNA impact. Current methods ignore the multiple dynamical 'themes'-in the form of enriched biologically relevant microRNA-mediated subpathways-that determine the functionality of signaling networks across time. To address these challenges, we developed time-vaRying enriCHment integrOmics Subpathway aNalysis tOol (CHRONOS) by integrating time series mRNA/microRNA expression data with KEGG pathway maps and microRNA-target interactions. Specifically, microRNA-mediated subpathway topologies are extracted and evaluated based on the temporal transition and the fold change activity of the linked genes/microRNAs. Further, we provide measures that capture the structural and functional features of subpathways in relation to the complete organism pathway atlas. Our application to synthetic and real data shows that CHRONOS outperforms current subpathway-based methods into unraveling the inherent dynamic properties of pathways. CHRONOS is freely available at http://biosignal.med.upatras.gr/chronos/ tassos.bezerianos@nus.edu.sg Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mechanism evaluation of a lifestyle intervention for patients with musculoskeletal pain who are overweight or obese: protocol for a causal mediation analysis

PubMed Central

Lee, Hopin; Wiggers, John; Kamper, Steven J; Williams, Amanda; O'Brien, Kate M; Hodder, Rebecca K; Yoong, Sze Lin; Campbell, Elizabeth; Haskins, Robin; Robson, Emma K; McAuley, James H; Williams, Christopher M

2017-01-01

Introduction Low back pain (LBP) and knee osteoarthritis (OA) are highly prevalent and disabling conditions that cause societal and economic impact worldwide. Two randomised controlled trials (RCTs) will evaluate the effectiveness of a multicomponent lifestyle intervention for patients with LBP and knee OA who are overweight or obese. The key targets of this intervention are to improve physical activity, modify diet and correct pain beliefs. These factors may explain how a lifestyle intervention exerts its effects on key patient-relevant outcomes: pain, disability and quality of life. The aim of this protocol is to describe a planned analysis of a mechanism evaluation for a lifestyle intervention for overweight or obese patients with LBP and knee OA. Methods and analysis Causal mediation analyses of 2 two-armed RCTs. Both trials are part of a cohort-multiple RCT, embedded in routine health service delivery. In each respective trial, 160 patients with LBP and 120 patients with knee OA waiting for orthopaedic consultation will be randomised to a lifestyle intervention, or to remain part of the original cohort. The intervention consists of education and advice about the benefits of weight loss and physical activity, and the Australian New South Wales Get Healthy Service. All outcome measures including patient characteristics, primary and alternative mediators, outcomes, and potential confounders will be measured at baseline (T0). The primary mediator, weight, will be measured at 6 months post randomisation; alternative mediators including diet, physical activity and pain beliefs will be measured at 6 weeks post randomisation. All outcomes (pain, disability and quality of life) will be measured at 6 months post randomisation. Data will be analysed using causal mediation analysis with sensitivity analyses for sequential ignorability. All mediation models were specified a priori before completing data collection and without prior knowledge about the effectiveness of the intervention. Ethics and dissemination The study is approved by the Hunter New England Health Human Research Ethics Committee (13/12/11/5.18) and the University of Newcastle Human Research Ethics Committee (H-2015–0043). The results will be disseminated in peer-reviewed journals and at scientific conferences. Trial registration number ACTRN12615000490572 and ACTRN12615000478516; Pre-results. PMID:28674135

Prospects for discovery by epigenome comparison

PubMed Central

Milosavljevic, Aleksandar

2010-01-01

Epigenomic analysis efforts have so far focused on the multiple layers of epigenomic information within individual cell types. With the rapidly increasing diversity of epigenomically mapped cell types, unprecedented opportunities for comparative analysis of epigenomes are opening up. One such opportunity is to map the bifurcating tree of cellular differentiation. Another is to understand the epigenomically mediated effects of mutations, environmental influences, and disease processes. Comparative analysis of epigenomes therefore has the potential to provide wide-ranging fresh insights into basic biology and human disease. The realization of this potential will critically depend on availability of a cyberinfrastructure that will scale with the volume of data and diversity of applications and a number of other computational challenges. PMID:20944597

The Role of Body Image in the Relationship Between Internet Use and Bulimic Symptoms: Three Theoretical Frameworks.

PubMed

Melioli, Tiffany; Rodgers, Rachel F; Rodrigues, Marie; Chabrol, Henri

2015-11-01

Exposure to traditional media has been associated with bulimic symptoms. However, to date, little is known regarding the effects of Internet exposure. The aim of this study was to explore the relationships between Internet use and bulimic symptoms within the competing frameworks of sociocultural, impression management, and self-objectification theory. A sample of 289 French women aged 18-25 years completed an online questionnaire assessing bulimic symptoms, body dissatisfaction, body image avoidance, self-surveillance, body shame, and weekly Internet use. Bootstrapping analyses revealed that body shame and body image avoidance mediated the effect of weekly Internet use on bulimic symptoms. Furthermore, when entered into a multiple mediation analysis, these two variables provided independent mediation pathways of equal magnitude. The findings support the usefulness of both the self-objectification and impression management frameworks for investigating the relationship between Internet use and bulimic symptoms. Longitudinal research would help to clarify these pathways further.

Can community consciousness be a bad thing? A moderated mediation analysis of heterosexism, mental health, and body appreciation in sexual minority men

PubMed Central

Simpson, Courtney C.; Sutter, Megan; Perrin, Paul B.

2016-01-01

This study examined the connections among heterosexism, mental health, body appreciation, and community consciousness in sexual minority men. Participants (N = 89) completed a national online survey. Simultaneous multiple regression found that heterosexism explained 9.4% of the variance in body appreciation and 25.8% of the variance in mental health; mental health accounted for 28.0% of the variance in body appreciation. Within these models, harassment/rejection heterosexism was a unique positive predictor of mental health and a unique negative predictor of body appreciation; depression was a unique negative predictor of body appreciation. A moderated mediational model found that depression mediated the relationship between harassment/rejection heterosexism and body appreciation, but only in men who endorsed high community consciousness. Intervention research might benefit from helping sexual minority men explore the ways in which body image is affected by heterosexism and mental health, as well as the ways that contemporary Western gay communities might contribute to these connections. PMID:27210047

Tailoring partially reduced graphene oxide as redox mediator for enhanced biotransformation of iopromide under methanogenic and sulfate-reducing conditions.

PubMed

Toral-Sánchez, Eduardo; Rangel-Mendez, J Rene; Ascacio Valdés, Juan A; Aguilar, Cristóbal N; Cervantes, Francisco J

2017-01-01

This work reports the first successful application of graphene oxide (GO) and partially reduced GO (rGO) as redox mediator (RM) to increase the biotransformation of the recalcitrant iodinated contrast medium, iopromide (IOP). Results showed that GO-based materials promoted up to 5.5 and 2.8-fold faster biotransformation of IOP by anaerobic sludge under methanogenic and sulfate-reducing conditions, respectively. Correlation between the extent of reduction of GO and its redox-mediating capacity was demonstrated, which was reflected in faster removal and greater extent of biotransformation of IOP. Further analysis indicated that the biotransformation pathway of IOP involved multiple reactions including deiodination, decarboxylation, demethylation, dehydration and N-dealkylation. GO-based materials could be strategically tailored and integrated in biological treatment systems to effectively enhance the redox conversion of recalcitrant pollutants commonly found in wastewater treatment systems and industrial effluents. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Importance of Emotional Intelligence and Cognitive Style in Institutionalized Older Adults' Quality of Life.

PubMed

Luque-Reca, Octavio; Pulido-Martos, Manuel; Lopez-Zafra, Esther; Augusto-Landa, José M

2018-01-01

Despite previous evidence showing a positive relationship between emotional intelligence (EI) and quality of life (QoL), associating older adults' emotional processing with several health indicators, few studies have explored both the IE and the a mechanisms through which they affect QoL. This cross-sectional study analyzes the mediator role of optimistic and pessimistic cognitive styles in the relationship between perceived EI (PEI) and QoL in 115 institutionalized older adults from Southern Spain. Regression analyses showed, after controlling for cognitive style, that PEI predicted a significant percentage of variance in: Health (β = .25, p < .01), Functional abilities (β = .20, p < .05), Activity and leisure (β = .17, p < .05) and Life satisfaction (β = .21, p < .05). Additionally, multiple mediation analysis revealed that cognitive style partially mediated the relationship between PEI and Health, Activity and leisure and Life satisfaction. Thus, PEI could promote personal but not external or environmental QoL aspects, highlighting the importance of developing emotional skills for healthy aging.

Can community consciousness be a bad thing? A moderated mediation analysis of heterosexism, mental health and body appreciation in sexual minority men.

PubMed

Simpson, Courtney C; Sutter, Megan; Perrin, Paul B

2016-11-01

This study examined the connections between heterosexism, mental health, body appreciation and community consciousness in sexual minority men (SMM). Participants (n = 89) completed a national online survey. Simultaneous multiple regressions found that heterosexism explained 9.4% of the variance in body appreciation and 25.8% of the variance in mental health; mental health accounted for 28.0% of the variance in body appreciation. Within these models, harassment/rejection heterosexism was a unique positive predictor of mental health problems and a unique negative predictor of body appreciation; depression was a unique negative predictor of body appreciation. A moderated mediational model found that depression mediated the relationship between harassment/rejection heterosexism and body appreciation, but only in men who endorsed high community consciousness. Intervention research might benefit from helping SMM explore the ways in which body image is affected by heterosexism and mental health, as well as the ways that contemporary Western gay communities might contribute to these connections.

Humanizing Outgroups Through Multiple Categorization

PubMed Central

Prati, Francesca; Crisp, Richard J.; Meleady, Rose; Rubini, Monica

2016-01-01

In three studies, we examined the impact of multiple categorization on intergroup dehumanization. Study 1 showed that perceiving members of a rival university along multiple versus simple categorical dimensions enhanced the tendency to attribute human traits to this group. Study 2 showed that multiple versus simple categorization of immigrants increased the attribution of uniquely human emotions to them. This effect was explained by the sequential mediation of increased individuation of the outgroup and reduced outgroup threat. Study 3 replicated this sequential mediation model and introduced a novel way of measuring humanization in which participants generated attributes corresponding to the outgroup in a free response format. Participants generated more uniquely human traits in the multiple versus simple categorization conditions. We discuss the theoretical implications of these findings and consider their role in informing and improving efforts to ameliorate contemporary forms of intergroup discrimination. PMID:26984016

Proteome analysis of Arabidopsis seedlings exposed to bacterial volatiles.

PubMed

Kwon, Young Sang; Ryu, Choong-Min; Lee, Soohyun; Park, Hyo Bee; Han, Ki Soo; Lee, Jung Han; Lee, Kyunghee; Chung, Woo Sik; Jeong, Mi-Jeong; Kim, Hee Kyu; Bae, Dong-Won

2010-11-01

Plant root-associated bacteria (rhizobacteria) elicit plant basal immunity referred to as induced systemic resistance (ISR) against multiple pathogens. Among multi-bacterial determinants involving such ISR, the induction of ISR and promotion of growth by bacterial volatile compounds was previously reported. To exploit global de novo expression of plant proteins by bacterial volatiles, proteomic analysis was performed after exposure of Arabidopsis plants to the rhizobacterium Bacillus subtilis GB03. Ethylene biosynthesis enzymes were significantly up-regulated. Analysis by quantitative reverse transcriptase polymerase chain reaction confirmed that ethylene biosynthesis-related genes SAM-2, ACS4, ACS12, and ACO2 as well as ethylene response genes, ERF1, GST2, and CHIB were up-regulated by the exposure to bacterial volatiles. More interestingly, the emission of bacterial volatiles significantly up-regulated both key defense mechanisms mediated by jasmonic acid and salicylic acid signaling pathways. In addition, high accumulation of antioxidant proteins also provided evidence of decreased sensitivity to reactive oxygen species during the elicitation of ISR by bacterial volatiles. The present results suggest that the proteomic analysis of plant defense responses in bacterial volatile-mediated ISR can reveal the mechanisms of plant basal defenses orchestrated by endogenous ethylene production pathways and the generation of reactive oxygen species.

Interrelationships among mediators of cellular zinc homeostasis in healthy and type 2 diabetes mellitus populations.

PubMed

Chu, Anna; Foster, Meika; Hancock, Dale; Petocz, Peter; Samman, Samir

2017-04-01

The involvement of zinc in multiple physiological systems requires tight control of cellular zinc concentration. This study aims to explore the relationships among selected mediators of cellular zinc homeostasis in an apparently healthy (AH) population and a cohort with type 2 diabetes mellitus (T2DM). Baseline data of three trials forming two cohorts, AH (n = 70) and T2DM (n = 42), were used for multivariate analyses to identify groupings within ten zinc transporter and metallothionein (MT) gene expressions, stratified by health status. Multiple regression models were used to explore relationships among zinc transporter/MT groupings and plasma zinc. Gene expression of zinc transporters and MTs, with the exception of ZnT6, were significantly lower in the T2DM cohort (p < 0.01). Cluster analysis showed that the groupings of zinc transporters and MTs were largely similar between the two cohorts, with the exception for ZnT1 and ZIP7. Zinc transporters and MTs were significant determinants of plasma zinc (r 2 = 0.48, p = 0.001) in the AH cohort, but not in the T2DM cohort. The current study suggests altered cellular zinc homeostasis in T2DM and supports the use of multiple zinc transporters and MTs groupings to further understand zinc homeostasis in health and T2DM. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characteristics of the Chinese rural elderly living in nursing homes who have suicidal ideation: A multiple regression model.

PubMed

Zhang, Dan; Yang, Yang; Sun, Yaoyao; Wu, Menglian; Xie, Hui; Wang, Kefang; Zhang, Jie; Jia, Jihui; Su, Yonggang

Chinese rural elderly are at higher risk of committing suicide. However, little is known about the suicidal ideation (SI) of institutional elderly residents in rural China. 250 participants aged 60 or above living in Chinese rural nursing homes were recruited. Data were collected on subjects' SI, social-demographic characters, physical illness and psychological factors. Univariate comparisons and path analysis were conducted then. 19.5% (40/205) of the participants reported a current SI. Hopelessness and depression had significant direct impacts on SI, and self-esteem and loneliness can impact SI through the mediating of depression and hopelessness. Visiting frequency of children, number of physical illnesses and social activities can also affect SI through the mediating of loneliness or self-esteem. As the first study on path analysis of SI of rural institutional elderly, the findings are significant. All these factors in our model should be considered when interventions are being conducted. Copyright © 2017 Elsevier Inc. All rights reserved.

Unsupervised Discovery of Demixed, Low-Dimensional Neural Dynamics across Multiple Timescales through Tensor Component Analysis.

PubMed

Williams, Alex H; Kim, Tony Hyun; Wang, Forea; Vyas, Saurabh; Ryu, Stephen I; Shenoy, Krishna V; Schnitzer, Mark; Kolda, Tamara G; Ganguli, Surya

2018-06-27

Perceptions, thoughts, and actions unfold over millisecond timescales, while learned behaviors can require many days to mature. While recent experimental advances enable large-scale and long-term neural recordings with high temporal fidelity, it remains a formidable challenge to extract unbiased and interpretable descriptions of how rapid single-trial circuit dynamics change slowly over many trials to mediate learning. We demonstrate a simple tensor component analysis (TCA) can meet this challenge by extracting three interconnected, low-dimensional descriptions of neural data: neuron factors, reflecting cell assemblies; temporal factors, reflecting rapid circuit dynamics mediating perceptions, thoughts, and actions within each trial; and trial factors, describing both long-term learning and trial-to-trial changes in cognitive state. We demonstrate the broad applicability of TCA by revealing insights into diverse datasets derived from artificial neural networks, large-scale calcium imaging of rodent prefrontal cortex during maze navigation, and multielectrode recordings of macaque motor cortex during brain machine interface learning. Copyright © 2018 Elsevier Inc. All rights reserved.

Apricot (Prunus armeniaca L.).

PubMed

Petri, César; Alburquerque, Nuria; Burgos, Lorenzo

2015-01-01

A protocol for Agrobacterium-mediated stable transformation of whole leaf explants of the apricot (Prunus armeniaca) cultivars 'Helena' and 'Canino' is described. Regenerated buds were selected using a two-step selection strategy with paromomycin sulfate and transferred to bud multiplication medium 1 week after they were detected for optimal survival. After buds were transferred to bud multiplication medium, antibiotic was changed to kanamycin and concentration increased gradually at each transfer to fresh medium in order to eliminate possible escapes and chimeras. Transformation efficiency, based on PCR analysis of individual putative transformed shoots from independent lines, was 5.6%. Green and healthy buds, surviving high kanamycin concentration, were transferred to shoot multiplication medium where they elongated in shoots and proliferated. Elongated transgenic shoots were rooted in a medium containing 70 μM kanamycin. Rooted plants were acclimatized following standard procedures. This constitutes the only transformation protocol described for apricot clonal tissues and one of the few of Prunus.

Abl Tyrosine Kinase Phosphorylates Nonmuscle Myosin Light Chain Kinase to Regulate Endothelial Barrier Function

PubMed Central

Dudek, Steven M.; Chiang, Eddie T.; Camp, Sara M.; Guo, Yurong; Zhao, Jing; Brown, Mary E.; Singleton, Patrick A.; Wang, Lichun; Desai, Anjali; Arce, Fernando T.; Lal, Ratnesh; Van Eyk, Jennifer E.; Imam, Syed Z.

2010-01-01

Nonmuscle myosin light chain kinase (nmMLCK), a multi-functional cytoskeletal protein critical to vascular homeostasis, is highly regulated by tyrosine phosphorylation. We identified multiple novel c-Abl–mediated nmMLCK phosphorylation sites by mass spectroscopy analysis (including Y231, Y464, Y556, Y846) and examined their influence on nmMLCK function and human lung endothelial cell (EC) barrier regulation. Tyrosine phosphorylation of nmMLCK increased kinase activity, reversed nmMLCK-mediated inhibition of Arp2/3-mediated actin polymerization, and enhanced binding to the critical actin-binding phosphotyrosine protein, cortactin. EC challenge with sphingosine 1-phosphate (S1P), a potent barrier-enhancing agonist, resulted in c-Abl and phosphorylated nmMLCK recruitment into caveolin-enriched microdomains, rapid increases in Abl kinase activity, and spatial targeting of c-Abl to barrier-promoting cortical actin structures. Conversely, reduced c-Abl expression in EC (siRNA) markedly attenuated S1P-mediated cortical actin formation, reduced the EC modulus of elasticity (assessed by atomic force microscopy), reduced nmMLCK and cortactin tyrosine phosphorylation, and attenuated S1P-mediated barrier enhancement. These studies indicate an essential role for Abl kinase in vascular barrier regulation via posttranslational modification of nmMLCK and strongly support c-Abl-cortactin-nmMLCK interaction as a novel determinant of cortical actin-based cytoskeletal rearrangement critical to S1P-mediated EC barrier enhancement. PMID:20861316

Self-management and quality of life in chronic obstructive pulmonary disease (COPD): The mediating effects of positive affect.

PubMed

Benzo, Roberto P; Abascal-Bolado, Beatriz; Dulohery, Megan M

2016-04-01

This study aimed to increase our understanding of general self-management (SM) abilities in COPD by determining if SM can predict disease specific quality of life (QoL), by investigating whether specific SM domains are significant in COPD and by exploring the mediating effect of the positive/negative affect in the association between SM and QoL. Cross-sectional study based on 292 patients with COPD. Measures included demographics, lung function, gait speed, health care utilization, positive/negative affect, SM abilities, breathlessness and disease specific QoL. We performed, correlation, multiple regression models and mediation analysis (positive/negative affect being mediator between SM and QoL association). After controlling for breathlessness, living alone, marital status, hospitalization history, age and lung function, SM related to QoL (p<0.0001). Investment in behaviors (hobbies and social relationships) and self-efficacy are SM domains independently related to QoL in COPD. Positivity measured by the positive/negative affect ratio completely mediates the relationship of SM with QoL. SM is independently associated with disease specific QoL in COPD after adjustment significant covariates but positive/negative affect ratio completely mediates the relationship of SM with QoL. Measuring positive/negative affect and addressing investment behavior and self-efficacy are important in implementing COPD-SM programs. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Examining the Associations Among Home-School Dissonance, Amotivation, and Classroom Disruptive Behavior for Urban High School Students.

PubMed

Brown-Wright, Lynda; Tyler, Kenneth M; Graves, Scott L; Thomas, Deneia; Stevens-Watkins, Danelle; Mulder, Shambra

2013-01-01

The current study examined the association among home-school dissonance, amotivation, and classroom disruptive behavior among 309 high school juniors and seniors at two urban high schools in the Southern region of the country. Students completed two subscales of the Patterns of Learning Activities Scales (PALS) and one subscale of the Academic Motivation Scale (AMS). ANCOVA analyses revealed significant differences in classroom disruptive behaviors for the gender independent variable. Controlling for gender in the multiple hierarchical regression analyses, it was revealed that home-school dissonance significantly predicted both amotivation and classroom disruptive behavior. In addition, a Sobel mediation analysis showed that amotivation was a significant mediator of the association between home-school dissonance and classroom disruptive behavior. Findings and limitations are discussed.

Examining the Associations Among Home–School Dissonance, Amotivation, and Classroom Disruptive Behavior for Urban High School Students

PubMed Central

Brown-Wright, Lynda; Tyler, Kenneth M.; Graves, Scott L.; Thomas, Deneia; Stevens-Watkins, Danelle; Mulder, Shambra

2015-01-01

The current study examined the association among home–school dissonance, amotivation, and classroom disruptive behavior among 309 high school juniors and seniors at two urban high schools in the Southern region of the country. Students completed two subscales of the Patterns of Learning Activities Scales (PALS) and one subscale of the Academic Motivation Scale (AMS). ANCOVA analyses revealed significant differences in classroom disruptive behaviors for the gender independent variable. Controlling for gender in the multiple hierarchical regression analyses, it was revealed that home–school dissonance significantly predicted both amotivation and classroom disruptive behavior. In addition, a Sobel mediation analysis showed that amotivation was a significant mediator of the association between home–school dissonance and classroom disruptive behavior. Findings and limitations are discussed. PMID:27081213

Postage for the messenger: Designating routes for Nuclear mRNA Export

PubMed Central

Natalizio, Barbara J.; Wente, Susan R.

2013-01-01

Transcription of messenger(m) RNA occurs in the nucleus, making the translocation of mRNA across the nuclear envelope (NE) boundary a critical determinant of proper gene expression and cell survival. A major mRNA export route occurs via the NXF1-dependent pathway through the nuclear pore complexes (NPCs) embedded in the NE. However, recent findings have discovered new evidence supporting the existence of multiple mechanisms for crossing the NE, including both NPC-mediated and NE budding-mediated pathways. An analysis of the trans-acting factors and cis components that define these pathways reveals shared elements as well as mechanistic differences. We review here the current understanding of the mechanisms that characterize each pathway and highlight the determinants that influence mRNA transport fate. PMID:23583578

Quantifying oncogenic phosphotyrosine signaling networks through systems biology.

PubMed

Del Rosario, Amanda M; White, Forest M

2010-02-01

Pathways linking oncogenic mutations to increased proliferative or migratory capacity are poorly characterized, yet provide potential targets for therapeutic intervention. As tyrosine phosphorylation signaling networks are known to mediate proliferation and migration, and frequently go awry in cancers, a comprehensive understanding of these networks in normal and diseased states is warranted. To this end, recent advances in mass spectrometry, protein microarrays, and computational algorithms provide insight into various aspects of the network including phosphotyrosine identification, analysis of kinase/phosphatase substrates, and phosphorylation-mediated protein-protein interactions. Here we detail technological advances underlying these system-level approaches and give examples of their applications. By combining multiple approaches, it is now possible to quantify changes in the phosphotyrosine signaling network with various oncogenic mutations, thereby unveiling novel therapeutic targets. Copyright 2009 Elsevier Ltd. All rights reserved.

Inhibition of cell-mediated immunity by the histone deacetylase inhibitor vorinostat: implications for therapy of cutaneous T-cell lymphoma.

PubMed

Stephen, Sasha; Morrissey, Kelly A; Benoit, Bernice M; Kim, Ellen J; Vittorio, Carmela C; Nasta, Sunita D; Showe, Louise C; Wysocka, Maria; Rook, Alain H

2012-02-01

Several histone deacetylase inhibitors (HDACi), including vorinostat, have been approved for the therapy of cutaneous T-cell lymphoma (CTCL). Emerging data suggest that HDACi may exert immune suppressive effects which would be disadvantageous for therapy of CTCL. We describe a patient with Sezary syndrome who was monitored for drug-induced immunosuppression while undergoing treatment with vorinostat. Analysis of the patient's natural killer cell function before and after initiation of treatment confirmed inhibition of this important cell-mediated immune function. In addition, the in vitro effects of vorinostat on the immunity of healthy volunteers confirmed that this class of drug can profoundly suppress multiple arms of the cellular immune response. These findings raise concerns of increased susceptibility to infection in this high-risk population.

Latino adolescents' academic success: the role of discrimination, academic motivation, and gender.

PubMed

Alfaro, Edna C; Umaña-Taylor, Adriana J; Gonzales-Backen, Melinda A; Bámaca, Mayra Y; Zeiders, Katharine H

2009-08-01

Guided by the academic resilience perspective, the current longitudinal study examined whether academic motivation mediated the relation between Latino adolescents' (N=221) experiences with discrimination and their academic success. The potential moderating role of gender was also examined. Using multiple group analysis in structural equation modeling, findings indicated that perceived discrimination at Wave 2 significantly predicted academic motivation at Waves 2 and 3 for boys but not girls. Additionally, for boys, academic motivation significantly mediated the relation between perceived discrimination and academic success. Findings underscore the importance of considering the long-term implications of discrimination for Latino boys' academic success. Furthermore, findings encourage moving beyond the examination of gender differences in specific academic outcomes (e.g., academic success) and focusing on how the processes leading to academic success vary by gender.

Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex.

PubMed

Tuttle, Lisa M; Pacheco, Derek; Warfield, Linda; Luo, Jie; Ranish, Jeff; Hahn, Steven; Klevit, Rachel E

2018-03-20

Transcription activation domains (ADs) are inherently disordered proteins that often target multiple coactivator complexes, but the specificity of these interactions is not understood. Efficient transcription activation by yeast Gcn4 requires its tandem ADs and four activator-binding domains (ABDs) on its target, the Mediator subunit Med15. Multiple ABDs are a common feature of coactivator complexes. We find that the large Gcn4-Med15 complex is heterogeneous and contains nearly all possible AD-ABD interactions. Gcn4-Med15 forms via a dynamic fuzzy protein-protein interface, where ADs bind the ABDs in multiple orientations via hydrophobic regions that gain helicity. This combinatorial mechanism allows individual low-affinity and specificity interactions to generate a biologically functional, specific, and higher affinity complex despite lacking a defined protein-protein interface. This binding strategy is likely representative of many activators that target multiple coactivators, as it allows great flexibility in combinations of activators that can cooperate to regulate genes with variable coactivator requirements. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Depression, anxiety and loss of resilience after multiple traumas: an illustration of a mediated moderation model of sensitization in a group of children who survived the Nazi Holocaust.

PubMed

Fossion, Pierre; Leys, Christophe; Kempenaers, Chantal; Braun, Stephanie; Verbanck, Paul; Linkowski, Paul

2013-12-01

Depressive and anxiety disorders (DAD) have become a major public health problem. Multiple trauma is known to increase the risk of DAD through a sensitization mechanism. We investigate the hypothesis that resilience is a mediator of this mechanism. Former Hidden Children (FHC), the Jewish youths who spent World War II in various hideaway shelters across Nazi-occupied Europe, were compared with a control group. In each group, we measured the presence of multiple traumas, the resilience with the Resilience Scale for Adults, which has a six factors solution, and the DAD with the Hopkins Symptoms Checklist. We test a mediated moderation model with childhood trauma as the predictor; Later trauma as the moderator; Resilience as the mediator; and DAD as the outcome variable. Results are consistent with a sensitization model of DAD mediated by resilience: confrontation with a primary trauma during childhood followed by secondary trauma(s) after childhood damages resilience, which, in turn, results in higher level of DAD. We are unable to differentiate if the sensitization process is a consequence of the nature of the trauma endured by FHC (long-standing exposure to extreme external events) or a consequence of the fact that this first trauma occurred during childhood. Resilience construct is multi-factorial and a limited damaging of some of the factors is sufficient to lead to DAD even if other factors remain unaltered. Resilience can be altered by multiple traumas and, therefore, needs to be bolstered in therapy sessions. Copyright © 2013. Published by Elsevier B.V.

[Effects of Korean proficiency and parent-child cohesion on self-esteem and acculturation among children from multicultural families].

PubMed

Kim, Mi Ye; Lim, Ji Young; Chung, Grace H

2012-12-01

There is evidence that parent-child cohesion is a potentially influential factor in children's self-esteem and acculturation. However, no research to date has examined cohesion with parents as a potential pathway between Korean proficiency and self-esteem or acculturation among children from multicultural families. This study was done to address these limitations by examining whether and to what extent cohesion with parents mediated the effect of Korean proficiency on self-esteem and acculturation among children from multicultural families. Data were collected from a sample of 138 mothers and their children living in Seoul, Daegu, Kyungi province, and Kyungpook province. Multiple regression analysis was used to examine the relationships between the variables of interest. Mediation effects of cohesion with parents were tested by following the procedure recommended by Baron and Kenny (1986). Cohesion with parents partially mediated the relationship between Korean proficiency and self-esteem. For children's acculturation, the effect of Korean proficiency was partially mediated through father-child cohesion. Mother-child cohesion completely mediated the relationship between Korean proficiency and acculturation. These findings suggest that to help children from multicultural families experiencing difficulties with self-esteem or acculturation, it might be useful to develop programs that are aimed at strengthen cohesion with parents.

Can Job Control Ameliorate Work-family Conflict and Enhance Job Satisfaction among Chinese Registered Nurses? A Mediation Model.

PubMed

Ding, Xiaotong; Yang, Yajuan; Su, Dan; Zhang, Ting; Li, Lunlan; Li, Huiping

2018-04-01

Low job satisfaction is the most common cause of nurses' turnover and influences the quality of nursing service. Moreover, we have no idea regarding whether job control, as an individual factor, can play a role in the relationship. To explore the relationship between work-family conflict and job satisfaction among Chinese registered nurses and the mediating role of job control in this relationship. From August 2015 to November 2016, 487 Chinese registered nurses completed a survey. The study used work-family conflict scale, job control scale, job satisfaction scale, as well as general information. Multiple regression analysis was used to explore the independent factors of job satisfaction. Structural equation model was used to explore the mediating role of job control. Work-family conflict was negatively correlated with job satisfaction (r ‑0.432, p<0.01). In addition, job control was positively related to job satisfaction (r 0.567, p<0.01). Work-family conflict and job control had significant predictive effects on job satisfaction. Job control partially mediated the relationship between work-family conflict and job satisfaction. Work-family conflict affected job satisfaction and job control was a mediator in this relationship among Chinese registered nurses. Job control could potentially improve nurses' job satisfaction.

Emotional eating as a mediator between anxiety and cholesterol in population with overweight and hypertension.

PubMed

Mensorio, Marinna S; Cebolla, Ausiàs; Lisón, Juan Francisco; Rodilla, Enrique; Palomar, Gonzalo; Miragall, Marta; Baños, Rosa Maria

2017-09-01

Although the relationship between cholesterol and mood states (especially anxiety) has been well studied, few researches have included the role of eating styles in this relationship. This study explored the associations among eating styles, negative emotional symptoms, and levels of cholesterol (and other medical variables) in a population with hypertension and overweight or obesity, analyzing the possible mediation mechanisms involved. A cross-sectional study was conducted in 68 adults with hypertension and overweight/obesity, and stepwise multiple regression analysis and mediation analyses were carried out to test the hypothesis that eating styles mediate the relationship between negative emotional symptoms and cholesterol. Several significant correlations among age, anthropometric, medical, and psychological variables (eating styles and negative emotional symptoms) were found. There was a significant indirect effect of anxiety on total cholesterol and LDL cholesterol through emotional eating. Results suggest that emotional eating has a relevant role in the rise in total and LDL cholesterol, acting as a mediator in the relationship between anxiety and cholesterol. This finding could have important implications, since it introduces a new variable in the relationship between emotions and cholesterol and, therefore, changes the way of understanding this relationship, and of treating high cholesterol in a hypertensive sample.

[Influence of Nurse Managers' Authentic Leadership on Nurses' Organizational Commitment and Job Satisfaction: Focused on the Mediating Effects of Empowerment].

PubMed

Choi, Han Gyo; Ahn, Sung Hee

2016-02-01

The aim of this study was to examine the mediating effect of empowerment in the relationship of nurse managers' authentic leadership, with nurses' organizational commitment and job satisfaction. The participants in this study were 273 registered nurses working in five University hospitals located in Seoul and Gyeonggi Province. The measurements included the Authentic Leadership Questionnaire, Condition of Work Effectiveness Questionnaire-II, Organizational Commitment Questionnaire and Korea-Minnesota Satisfaction Questionnaire. Data were analyzed using t-test, ANOVA, Scheffé test, Pearson correlation coefficients, simple and multiple regression techniques with the SPSS 18.0 program. Mediation analysis was performed according to the Baron and Kenny method and Sobel test. There were significant correlations among authentic leadership, empowerment, organizational commitment and job satisfaction. Empowerment showed perfect mediating effects in the relationship between authentic leadership and organizational commitment. It had partial mediating effects in the relationship between authentic leadership and job satisfaction. In this study, nurse managers' authentic leadership had significant influences on nurses organizational commitment and job satisfaction via empowerment. Therefore, to enhance nurses' organizational commitment and job satisfaction, it is necessary to build effective strategies to enhance nurse manager's authentic leadership and to develop empowering education programs for nurses.

The Presence of a Calling and Academic Satisfaction: Examining Potential Mediators

ERIC Educational Resources Information Center

Duffy, Ryan D.; Allan, Blake A.; Dik, Bryan J.

2011-01-01

The present study examined the relation of calling and academic satisfaction with a diverse sample of 312 undergraduate students. The presence of a calling was moderately correlated with academic satisfaction, and a multiple mediation model was utilized to test three potential mediators to this relation: career decision self-efficacy, work hope,…

Father Beliefs as a Mediator between Contextual Barriers and Father Involvement

ERIC Educational Resources Information Center

Freeman, Harry; Newland, Lisa A.; Coyl, Diana D.

2008-01-01

Fathers' beliefs were examined as mediators between multiple risk factors and involvement practices with children age zero to five enrolled in Head Start or Early Head Start. A diverse sample of 101 fathers, living in rural Midwestern communities of the USA completed questionnaires assessing "mediators" (i.e. parenting efficacy, role beliefs, and…

Transcription Profiles Reveal Sugar and Hormone Signaling Pathways Mediating Flower Induction in Apple (Malus domestica Borkh.).

PubMed

Xing, Li-Bo; Zhang, Dong; Li, You-Mei; Shen, Ya-Wen; Zhao, Cai-Ping; Ma, Juan-Juan; An, Na; Han, Ming-Yu

2015-10-01

Flower induction in apple (Malus domestica Borkh.) is regulated by complex gene networks that involve multiple signal pathways to ensure flower bud formation in the next year, but the molecular determinants of apple flower induction are still unknown. In this research, transcriptomic profiles from differentiating buds allowed us to identify genes potentially involved in signaling pathways that mediate the regulatory mechanisms of flower induction. A hypothetical model for this regulatory mechanism was obtained by analysis of the available transcriptomic data, suggesting that sugar-, hormone- and flowering-related genes, as well as those involved in cell-cycle induction, participated in the apple flower induction process. Sugar levels and metabolism-related gene expression profiles revealed that sucrose is the initiation signal in flower induction. Complex hormone regulatory networks involved in cytokinin (CK), abscisic acid (ABA) and gibberellic acid pathways also induce apple flower formation. CK plays a key role in the regulation of cell formation and differentiation, and in affecting flowering-related gene expression levels during these processes. Meanwhile, ABA levels and ABA-related gene expression levels gradually increased, as did those of sugar metabolism-related genes, in developing buds, indicating that ABA signals regulate apple flower induction by participating in the sugar-mediated flowering pathway. Furthermore, changes in sugar and starch deposition levels in buds can be affected by ABA content and the expression of the genes involved in the ABA signaling pathway. Thus, multiple pathways, which are mainly mediated by crosstalk between sugar and hormone signals, regulate the molecular network involved in bud growth and flower induction in apple trees. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

Nipbl and mediator cooperatively regulate gene expression to control limb development.

PubMed

Muto, Akihiko; Ikeda, Shingo; Lopez-Burks, Martha E; Kikuchi, Yutaka; Calof, Anne L; Lander, Arthur D; Schilling, Thomas F

2014-09-01

Haploinsufficiency for Nipbl, a cohesin loading protein, causes Cornelia de Lange Syndrome (CdLS), the most common "cohesinopathy". It has been proposed that the effects of Nipbl-haploinsufficiency result from disruption of long-range communication between DNA elements. Here we use zebrafish and mouse models of CdLS to examine how transcriptional changes caused by Nipbl deficiency give rise to limb defects, a common condition in individuals with CdLS. In the zebrafish pectoral fin (forelimb), knockdown of Nipbl expression led to size reductions and patterning defects that were preceded by dysregulated expression of key early limb development genes, including fgfs, shha, hand2 and multiple hox genes. In limb buds of Nipbl-haploinsufficient mice, transcriptome analysis revealed many similar gene expression changes, as well as altered expression of additional classes of genes that play roles in limb development. In both species, the pattern of dysregulation of hox-gene expression depended on genomic location within the Hox clusters. In view of studies suggesting that Nipbl colocalizes with the mediator complex, which facilitates enhancer-promoter communication, we also examined zebrafish deficient for the Med12 Mediator subunit, and found they resembled Nipbl-deficient fish in both morphology and gene expression. Moreover, combined partial reduction of both Nipbl and Med12 had a strongly synergistic effect, consistent with both molecules acting in a common pathway. In addition, three-dimensional fluorescent in situ hybridization revealed that Nipbl and Med12 are required to bring regions containing long-range enhancers into close proximity with the zebrafish hoxda cluster. These data demonstrate a crucial role for Nipbl in limb development, and support the view that its actions on multiple gene pathways result from its influence, together with Mediator, on regulation of long-range chromosomal interactions.

Making Sense of Bereavement in People with Profound Intellectual and Multiple Disabilities: Carer Perspectives.

PubMed

Young, Hannah; Hogg, James; Garrard, Brenda

2017-11-01

People with intellectual disabilities are thought to have a reduced capacity for understanding death. Drawing on cognitive theory, researchers have suggested that those with profound intellectual and multiple disabilities mainly perceive loss as a mismatch between past and present experiences. However, very little research has considered how carers conceptualize bereavement in relation to this group. Semi-structured interviews obtained responses from seven carers. Transcripts were examined using interpretative phenomenological analysis. Two superordinate themes emerged: 'difficulty articulating the experience of loss' and 'making sense of bereavement through familiar patterns'. Carers conceptualize bereavement primarily in cognitive terms, but also take account of relational factors mediating loss. Implications for training and further research are outlined. © 2016 John Wiley & Sons Ltd.

MicroRNA-133 mediates cardiac diseases: Mechanisms and clinical implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yi; Liang, Yan; Zhang, Jin-fang

MicroRNAs (miRNAs) belong to the family of small non-coding RNAs that mediate gene expression by post-transcriptional regulation. Increasing evidence have demonstrated that miR-133 is enriched in muscle tissues and myogenic cells, and its aberrant expression could induce the occurrence and development of cardiac disorders, such as cardiac hypertrophy, heart failure, etc. In this review, we summarized the regulatory roles of miR-133 in cardiac disorders and the underlying mechanisms, which suggest that miR-133 may be a potential diagnostic and therapeutic tool for cardiac disorders. - Highlights: • miR-218 is frequently downregulated in multiple cancers. • miR-218 plays pivotal roles in carcinogenesis.more » • miR-218 mediates proliferation, apoptosis, metastasis, invasion, etc. • miR-218 mediates tumorigenesis and metastasis via multiple pathways.« less

Parenting Behavior Mediates the Intergenerational Association of Parent and Child Offspring ADHD Symptoms

PubMed Central

Tung, Irene; Brammer, Whitney A.; Li, James J.; Lee, Steve S.

2015-01-01

Although there are likely to be multiple mechanisms underlying parent attention-deficit/hyperactivity disorder (ADHD) symptoms as a key risk factor for offspring ADHD, potential explanatory factors have yet to be reliably identified. Given that parent ADHD symptoms independently predict parenting behavior and child ADHD symptoms, we tested whether individual differences in multiple dimensions of positive and negative parenting behavior (i.e., corporal punishment, inconsistent discipline, positive parenting behavior, observed negative talk, and observed praise) mediated the association between parental and offspring ADHD. We used a prospective design that featured predictors (i.e., parent ADHD symptoms) and mediators (i.e., parenting behavior) that temporally preceded the outcome (i.e., offspring ADHD symptoms). Using a well-characterized sample of 120 children with and without ADHD (ages 5–10 at Wave 1, 7–12 at Wave 2) and their biological parents, we examined multimethod (i.e., observed, self-report) measures of positive and negative parenting behavior as simultaneous mediators of the association of Wave 1 parent and Wave 2 offspring ADHD symptoms. Using a multiple mediation framework, consisting of rigorous bootstrapping procedures and controlling for parent depression, child’s baseline ADHD and oppositional defiant disorder, and child’s age, corporal punishment significantly and uniquely mediated the association of Wave 1 parent ADHD symptoms and Wave 2 offspring ADHD. We consider the role of parenting behavior in the intergenerational transmission of ADHD as well as implications of these findings for the intervention and prevention of childhood ADHD. PMID:24926775

Parenting Behavior Mediates the Intergenerational Association of Parent and Child Offspring ADHD Symptoms.

PubMed

Tung, Irene; Brammer, Whitney A; Li, James J; Lee, Steve S

2015-01-01

Although there are likely to be multiple mechanisms underlying parent attention-deficit/hyperactivity disorder (ADHD) symptoms as a key risk factor for offspring ADHD, potential explanatory factors have yet to be reliably identified. Given that parent ADHD symptoms independently predict parenting behavior and child ADHD symptoms, we tested whether individual differences in multiple dimensions of positive and negative parenting behavior (i.e., corporal punishment, inconsistent discipline, positive parenting behavior, observed negative talk, and observed praise) mediated the association between parental and offspring ADHD. We used a prospective design that featured predictors (i.e., parent ADHD symptoms) and mediators (i.e., parenting behavior) that temporally preceded the outcome (i.e., offspring ADHD symptoms). Using a well-characterized sample of 120 children with and without ADHD (ages 5-10 at Wave 1, 7-12 at Wave 2) and their biological parents, we examined multimethod (i.e., observed, self-report) measures of positive and negative parenting behavior as simultaneous mediators of the association of Wave 1 parent and Wave 2 offspring ADHD symptoms. Using a multiple mediation framework, consisting of rigorous bootstrapping procedures and controlling for parent depression, child's baseline ADHD and oppositional defiant disorder, and child's age, corporal punishment significantly and uniquely mediated the association of Wave 1 parent ADHD symptoms and Wave 2 offspring ADHD. We consider the role of parenting behavior in the intergenerational transmission of ADHD as well as implications of these findings for the intervention and prevention of childhood ADHD.

Inflammatory Mediator Profiles Differ in Sepsis Patients With and Without Bacteremia.

PubMed

Mosevoll, Knut Anders; Skrede, Steinar; Markussen, Dagfinn Lunde; Fanebust, Hans Rune; Flaatten, Hans Kristian; Aßmus, Jörg; Reikvam, Håkon; Bruserud, Øystein

2018-01-01

Systemic levels of cytokines are altered during infection and sepsis. This prospective observational study aimed to investigate whether plasma levels of multiple inflammatory mediators differed between sepsis patients with and those without bacteremia during the initial phase of hospitalization. A total of 80 sepsis patients with proven bacterial infection and no immunosuppression were included in the study. Plasma samples were collected within 24 h of hospitalization, and Luminex ® analysis was performed on 35 mediators: 16 cytokines, six growth factors, four adhesion molecules, and nine matrix metalloproteases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs). Forty-two patients (52.5%) and 38 (47.5%) patients showed positive and negative blood cultures, respectively. There were significant differences in plasma levels of six soluble mediators between the two "bacteremia" and "non-bacteremia" groups, using Mann-Whitney U test ( p  < 0.0014): tumor necrosis factor alpha (TNFα), CCL4, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and TIMP-1. Ten soluble mediators also significantly differed in plasma levels between the two groups, with p -values ranging between 0.05 and 0.0014: interleukin (IL)-1ra, IL-10, CCL2, CCL5, CXCL8, CXCL11, hepatocyte growth factor, MMP-8, TIMP-2, and TIMP-4. VCAM-1 showed the most robust results using univariate and multivariate logistic regression. Using unsupervised hierarchical clustering, we found that TNFα, CCL4, E-selectin, VCAM-1, ICAM-1, and TIMP-1 could be used to discriminate between patients with and those without bacteremia. Patients with bacteremia were mainly clustered in two separate groups (two upper clusters, 41/42, 98%), with higher levels of the mediators. One (2%) patient with bacteremia was clustered in the lower cluster, which compromised most of the patients without bacteremia (23/38, 61%) (χ 2 test, p  < 0.0001). Our study showed that analysis of the plasma inflammatory mediator profile could represent a potential strategy for early identification of patients with bacteremia.

Targeting of the MUC1-C Oncoprotein in Colitis-Associated Colorectal Cancer

DTIC Science & Technology

2013-09-01

effect- level isobologram analysis is shown for ED 90 (), ED 75 (+) and ED 50 (×) with the right side panel indicating the CI index for the...was generated by exposing the cells to fixed IC50 ratios of GO-203, GSK1120212 and the GO- 203/GSK1120212 combination. The multiple effect- level ...Kharbanda S, and Kufe D, MUC1 oncoprotein blocks GSK3β -mediated phosphorylation and degradation of β-catenin. Cancer Res, 2005. 65:10413-22. 11. Rajabi

Sympathetic Nerves in Breast Cancer: Angiogenesis and Antiangiogenic Therapy

DTIC Science & Technology

2013-02-01

directly regulate 4T1 growth through ARs. Using in vitro conditions that yielded NE-mediated functional effects in other cell lines (1), we assessed...Therefore we propose that 4T1 is a good model for examining the effects of NE-induced effects on stromal cell populations in the absence of direct NE... effects analysis or by Holm-Sidak multiple comparison test. RESULTS 4T1 Tumor Cells Do Not Respond to NE In Vitro or Signal via AR To determine

Genomic Methods for Clinical and Translational Pain Research

PubMed Central

Wang, Dan; Kim, Hyungsuk; Wang, Xiao-Min; Dionne, Raymond

2012-01-01

Pain is a complex sensory experience for which the molecular mechanisms are yet to be fully elucidated. Individual differences in pain sensitivity are mediated by a complex network of multiple gene polymorphisms, physiological and psychological processes, and environmental factors. Here, we present the methods for applying unbiased molecular-genetic approaches, genome-wide association study (GWAS), and global gene expression analysis, to help better understand the molecular basis of pain sensitivity in humans and variable responses to analgesic drugs. PMID:22351080

Teacher’s Autonomy Support and Engagement in Math: Multiple Mediating Roles of Self-efficacy, Intrinsic Value, and Boredom

PubMed Central

Wang, Jia; Liu, Ru-De; Ding, Yi; Xu, Le; Liu, Ying; Zhen, Rui

2017-01-01

Previous studies have highlighted the impacts of environmental factors (teacher’s autonomy support) and individual factors (self-efficacy, intrinsic value, and boredom) on academic engagement. This study aimed to investigate these variables and examine the relations among them. Three structural equation models tested the multiple mediational roles of self-efficacy, intrinsic value, and boredom in the relation between teacher’s autonomy support and behavioral, emotional, and cognitive engagement, respectively, in math. A total of 637 Chinese middle school students (313 males, 324 females; mean age = 14.82) voluntarily participated in this study. Results revealed that self-efficacy, intrinsic value, and boredom played important and mediating roles between perceived teacher’s autonomy support and student engagement. Specifically, these three individual variables partly mediated the relations between perceived teacher’s autonomy support and behavioral and cognitive engagement, while fully mediating the relation between perceived teacher’s autonomy support and emotional engagement. These findings complement and extend the understanding of factors affecting students’ engagement in math. PMID:28690560

Teacher's Autonomy Support and Engagement in Math: Multiple Mediating Roles of Self-efficacy, Intrinsic Value, and Boredom.

PubMed

Wang, Jia; Liu, Ru-De; Ding, Yi; Xu, Le; Liu, Ying; Zhen, Rui

2017-01-01

Previous studies have highlighted the impacts of environmental factors (teacher's autonomy support) and individual factors (self-efficacy, intrinsic value, and boredom) on academic engagement. This study aimed to investigate these variables and examine the relations among them. Three structural equation models tested the multiple mediational roles of self-efficacy, intrinsic value, and boredom in the relation between teacher's autonomy support and behavioral, emotional, and cognitive engagement, respectively, in math. A total of 637 Chinese middle school students (313 males, 324 females; mean age = 14.82) voluntarily participated in this study. Results revealed that self-efficacy, intrinsic value, and boredom played important and mediating roles between perceived teacher's autonomy support and student engagement. Specifically, these three individual variables partly mediated the relations between perceived teacher's autonomy support and behavioral and cognitive engagement, while fully mediating the relation between perceived teacher's autonomy support and emotional engagement. These findings complement and extend the understanding of factors affecting students' engagement in math.

Prevention of ultraviolet-B radiation damage by resveratrol in mouse skin is mediated via modulation in survivin.

PubMed

Aziz, Moammir Hassan; Afaq, Farrukh; Ahmad, Nihal

2005-01-01

Nonmelanoma skin cancer is the most frequently diagnosed malignancy in the United States, and multiple exposures to solar ultraviolet (UV) radiation (particularly its UV-B component, 290-320 nm), is its major cause. 'Chemoprevention' by naturally occurring agents is being appreciated as a newer dimension in the management of neoplasia including skin cancer. We recently demonstrated that resveratrol (trans-3, 5, 4-trihydroxystilbene), an antioxidant found in grapes, red wines and a variety of nuts and berries, imparts protection from acute UV-B-mediated cutaneous damages in SKH-1 hairless mice. Understanding the mechanism of resveratrol-mediated protection of UV responses is important. We earlier demonstrated that resveratrol imparts chemopreventive effects against multiple UV-exposure-mediated modulations in (1) cki-cyclin-cdk network, and (2) mitogen activated protein kinase (MAPK)-pathway. This study was conducted to assess the involvement of inhibitor of apoptosis protein family Survivin during resveratrol-mediated protection from multiple exposures of UV-B (180 mJ/cm(2); on alternate days; for a total of seven exposures) radiations in the SKH-1 hairless mouse skin. Our data demonstrated that topical pre-treatment of resveratrol (10 micromol in 200 microl acetone/mouse) resulted in significant inhibition of UV-B exposure-mediated increases in (1) cellular proliferations (Ki-67 immunostaining), (2) protein levels of epidermal cyclooxygenase-2 and ornithine decarboxylase, established markers of tumor promotion, (3) protein and messenger RNA levels of Survivin, and (4) phosphorylation of survivin in the skin of SKH-1 hairless mouse. Resveratrol pretreatment also resulted in (1) reversal of UV-B-mediated decrease of Smac/DIABLO, and (2) enhancement of UV-B-mediated induction of apoptosis, in mouse skin. Taken together, our study suggested that resveratrol imparts chemopreventive effects against UV-B exposure-mediated damages in SKH-1 hairless mouse skin via inhibiting Survivin and the associated events.

Cloning and analysis of the positively acting regulatory gene amdR from Aspergillus nidulans.

PubMed Central

Andrianopoulos, A; Hynes, M J

1988-01-01

The positively acting regulatory gene amdR of Aspergillus nidulans coordinately regulates the expression of four unlinked structural genes involved in acetamide (amdS), omega amino acid (gatA and gabA), and lactam (lamA) catabolism. By the use of DNA-mediated transformation of A. nidulans, the amdR regulatory gene was cloned from a genomic cosmid library. Southern blot analysis of DNA from various loss-of-function amdR mutants revealed the presence of four detectable DNA rearrangements, including a deletion, an insertion, and a translocation. No detectable DNA rearrangements were found in several constitutive amdRc mutants. Analysis of the fate of amdR-bearing plasmids in transformants showed that 10 to 20% of the transformation events were homologous integrations or gene conversions, and this phenomenon was exploited in developing a strategy by which amdRc and amdR- alleles can be readily cloned and analyzed. Examination of the transcription of amdR by Northern blot (RNA blot) analysis revealed the presence of two mRNAs (2.7 and 1.8 kilobases) which were constitutively synthesized at a very low level. In addition, amdR transcription did not appear to depend on the presence of a functional amdR product nor was it altered in amdRc mutants. The dosage effects of multiple copies of amdR in transformants were examined, and it was shown that such transformants exhibited stronger growth than did the wild type on acetamide and pyrrolidinone media, indicating increased expression of the amdS and lamA genes, respectively. These results were used to formulate a model for amdR-mediated regulation of gene expression in which the low constitutive level of amdR product sets the upper limits of basal and induced transcription of the structural genes. Multiple copies of 5' sequences from the amdS gene can result in reduced growth on substrates whose utilization is dependent on amdR-controlled genes. This has been attributed to titration of limiting amdR gene product. Strong support for this proposal was obtained by showing that multiple copies of the amdR gene can reverse this phenomenon (antititration). Images PMID:3062382

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo.

PubMed

Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-10-30

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor.

PubMed

Anandhakumar, Jayamani; Moustafa, Yara W; Chowdhary, Surabhi; Kainth, Amoldeep S; Gross, David S

2016-07-15

Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the "anchor away" (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Mechanistic aspects of fluorescent gold nanocluster internalization by live HeLa cells

NASA Astrophysics Data System (ADS)

Yang, Linxiao; Shang, Li; Nienhaus, G. Ulrich

2013-01-01

We have studied cellular uptake of ultrasmall fluorescent gold nanoclusters (AuNCs) by HeLa cells by confocal fluorescence microscopy in combination with quantitative image analysis. Water solubilized, lipoic acid-protected AuNCs, which had an overall hydrodynamic diameter of 3.3 nm and emitted fluorescence in the near-infrared region at ~700 nm, were observed to accumulate on the cell membrane prior to internalization. The internalization mechanisms were analyzed using inhibitors known to interfere with specific pathways. Cellular uptake of AuNCs is energy-dependent and involves multiple mechanisms: clathrin-mediated endocytosis and macropinocytosis appear to play a significant role, whereas the caveolin-mediated pathway contributes only to a lesser extent. Co-labeling of different cell organelles showed that intracellular trafficking of AuNCs mainly follows through endosomal pathways. The AuNCs were ultimately transferred to lysosomes; they were completely excluded from the nucleus even after 24 h.We have studied cellular uptake of ultrasmall fluorescent gold nanoclusters (AuNCs) by HeLa cells by confocal fluorescence microscopy in combination with quantitative image analysis. Water solubilized, lipoic acid-protected AuNCs, which had an overall hydrodynamic diameter of 3.3 nm and emitted fluorescence in the near-infrared region at ~700 nm, were observed to accumulate on the cell membrane prior to internalization. The internalization mechanisms were analyzed using inhibitors known to interfere with specific pathways. Cellular uptake of AuNCs is energy-dependent and involves multiple mechanisms: clathrin-mediated endocytosis and macropinocytosis appear to play a significant role, whereas the caveolin-mediated pathway contributes only to a lesser extent. Co-labeling of different cell organelles showed that intracellular trafficking of AuNCs mainly follows through endosomal pathways. The AuNCs were ultimately transferred to lysosomes; they were completely excluded from the nucleus even after 24 h. Electronic supplementary information (ESI) available: Effect of serum on the AuNC uptake by HeLa cells and colocalization result of AuNCs with the cell nucleus for 2-24 h. See DOI: 10.1039/c2nr33147k

Improvements in emotion regulation following mindfulness meditation: Effects on depressive symptoms and perceived stress in younger breast cancer survivors.

PubMed

Boyle, Chloe C; Stanton, Annette L; Ganz, Patricia A; Crespi, Catherine M; Bower, Julienne E

2017-04-01

Mindfulness meditation reduces psychological distress among individuals with cancer. However, mechanisms for intervention effects have not been fully determined. This study tested emotion regulation strategies as mediators of intervention effects in a sample of younger women treated for breast cancer, a group at risk for psychological distress. We focused on two distinct strategies targeted by the intervention-rumination and self-kindness-and further examined the broader construct of mindfulness as a potential mediator. Women (n = 71) with Stage 0-III breast cancer diagnosed at or before age 50 who had completed cancer treatment were randomly assigned to a 6-week mindfulness intervention or wait-list control group. Assessments occurred at study entry, postintervention, and a 3-month follow-up. In single mediator analyses, increases in self-kindness (CIB [-7.83, -1.93]), decreases in rumination (CIB [-5.05, -.31]), and increases in mindfulness (CIB [-6.58, -.82]) each mediated reductions in depressive symptoms from pre- to postintervention. Increases in self-kindness also mediated reductions in perceived stress (CIB [-5.37, -.62]) from pre- to postintervention, and increases in self-kindness (CIB [-5.67, -.22]) and in mindfulness (CIB [-5.51, -.16]) each mediated intervention effects on perceived stress from preintervention to 3-month follow-up. In multiple mediator analysis, only self-kindness mediated intervention effects on depressive symptoms from pre- to postintervention (CIB [-6.41, -.61]), and self-kindness and mindfulness together mediated intervention effects on perceived stress from preintervention to follow-up (CIB [-6.77, -.35]). Self-kindness played a consistent role in reducing distress in younger women with breast cancer. The efficacy of this understudied emotion regulation strategy should be evaluated in other clinical populations. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A simple and novel method for RNA-seq library preparation of single cell cDNA analysis by hyperactive Tn5 transposase.

PubMed

Brouilette, Scott; Kuersten, Scott; Mein, Charles; Bozek, Monika; Terry, Anna; Dias, Kerith-Rae; Bhaw-Rosun, Leena; Shintani, Yasunori; Coppen, Steven; Ikebe, Chiho; Sawhney, Vinit; Campbell, Niall; Kaneko, Masahiro; Tano, Nobuko; Ishida, Hidekazu; Suzuki, Ken; Yashiro, Kenta

2012-10-01

Deep sequencing of single cell-derived cDNAs offers novel insights into oncogenesis and embryogenesis. However, traditional library preparation for RNA-seq analysis requires multiple steps with consequent sample loss and stochastic variation at each step significantly affecting output. Thus, a simpler and better protocol is desirable. The recently developed hyperactive Tn5-mediated library preparation, which brings high quality libraries, is likely one of the solutions. Here, we tested the applicability of hyperactive Tn5-mediated library preparation to deep sequencing of single cell cDNA, optimized the protocol, and compared it with the conventional method based on sonication. This new technique does not require any expensive or special equipment, which secures wider availability. A library was constructed from only 100 ng of cDNA, which enables the saving of precious specimens. Only a few steps of robust enzymatic reaction resulted in saved time, enabling more specimens to be prepared at once, and with a more reproducible size distribution among the different specimens. The obtained RNA-seq results were comparable to the conventional method. Thus, this Tn5-mediated preparation is applicable for anyone who aims to carry out deep sequencing for single cell cDNAs. Copyright © 2012 Wiley Periodicals, Inc.

Social support as a mediator between problem behaviour and gambling: a cross-sectional study among 14–16-year-old Finnish adolescents

PubMed Central

Lintonen, Tomi; Tolvanen, Asko; Konu, Anne

2016-01-01

Background During the adolescent period, risk-taking behaviour increases. These behaviours can compromise the successful transition from adolescence to adulthood. The purpose of this study was to examine social support as a mediator of the relation between problem behaviour and gambling frequency among Finnish adolescents. Methods Data were obtained from the national School Health Promotion Study (SHPS) from the years 2010 and 2011 (N=102 545). Adolescents were classified in the most homogeneous groups based on their problem behaviour via latent class analysis. Results Path analysis indicated that social support was negatively associated with problem behaviour, and problem behaviour and social support were negatively related (except for social support from friends among boys) to gambling. Social support from parents and school mediated, albeit weakly, the relations between problem behaviour and gambling among girls and boys. Conclusions Problem behaviour may affect gambling through social support from school and parents. Thus prevention and intervention strategies should focus on strengthening adolescents' social support. In addition, because of the clustering of different problem behaviours instead of concentrating on a single form of problem behaviour multiple-behaviour interventions may have a much greater impact on public health. PMID:28007707

A High-Confidence Interaction Map Identifies SIRT1 as a Mediator of Acetylation of USP22 and the SAGA Coactivator Complex

PubMed Central

Armour, Sean M.; Bennett, Eric J.; Braun, Craig R.; Zhang, Xiao-Yong; McMahon, Steven B.; Gygi, Steven P.; Harper, J. Wade

2013-01-01

Although many functions and targets have been attributed to the histone and protein deacetylase SIRT1, a comprehensive analysis of SIRT1 binding proteins yielding a high-confidence interaction map has not been established. Using a comparative statistical analysis of binding partners, we have assembled a high-confidence SIRT1 interactome. Employing this method, we identified the deubiquitinating enzyme ubiquitin-specific protease 22 (USP22), a component of the deubiquitinating module (DUBm) of the SAGA transcriptional coactivating complex, as a SIRT1-interacting partner. We found that this interaction is highly specific, requires the ZnF-UBP domain of USP22, and is disrupted by the inactivating H363Y mutation within SIRT1. Moreover, we show that USP22 is acetylated on multiple lysine residues and that alteration of a single lysine (K129) within the ZnF-UBP domain is sufficient to alter interaction of the DUBm with the core SAGA complex. Furthermore, USP22-mediated recruitment of SIRT1 activity promotes the deacetylation of individual SAGA complex components. Our results indicate an important role of SIRT1-mediated deacetylation in regulating the formation of DUBm subcomplexes within the larger SAGA complex. PMID:23382074

The Role of Health Care Provider and Partner Decisional Support in Patients' Cancer Treatment Decision-Making Satisfaction.

PubMed

Palmer-Wackerly, Angela L; Krieger, Janice L; Rhodes, Nancy D

2017-01-01

Cancer patients rely on multiple sources of support when making treatment decisions; however, most research studies examine the influence of health care provider support while the influence of family member support is understudied. The current study fills this gap by examining the influence of health care providers and partners on decision-making satisfaction. In a cross-sectional study via an online Qualtrics panel, we surveyed cancer patients who reported that they had a spouse or romantic partner when making cancer treatment decisions (n = 479). Decisional support was measured using 5-point, single-item scales for emotional support, informational support, informational-advice support, and appraisal support. Decision-making satisfaction was measured using Holmes-Rovner and colleagues' (1996) Satisfaction With Decision Scale. We conducted a mediated regression analysis to examine treatment decision-making satisfaction for all participants and a moderated mediation analysis to examine treatment satisfaction among those patients offered a clinical trial. Results indicated that partner support significantly and partially mediated the relationship between health care provider support and patients' decision-making satisfaction but that results did not vary by enrollment in a clinical trial. This study shows how and why decisional support from partners affects communication between health care providers and cancer patients.

How Multiple Social Identities Are Related to Creativity.

PubMed

Steffens, Niklas K; Gocłowska, Małgorzata A; Cruwys, Tegan; Galinsky, Adam D

2016-02-01

The present research examined whether possessing multiple social identities (i.e., groups relevant to one's sense of self) is associated with creativity. In Study 1, the more identities individuals reported having, the more names they generated for a new commercial product (i.e., greater idea fluency). In Study 2, multiple identities were associated with greater fluency and originality (mediated by cognitive flexibility, but not by persistence). Study 3 validated these findings using a highly powered sample. We again found that multiple identities increase fluency and originality, and that flexibility (but not persistence) mediated the effect on originality. Study 3 also ruled out several alternative explanations (self-affirmation, novelty seeking, and generalized persistence). Across all studies, the findings were robust to controlling for personality, and there was no evidence of a curvilinear relationship between multiple identities and creativity. These results suggest that possessing multiple social identities is associated with enhanced creativity via cognitive flexibility. © 2015 by the Society for Personality and Social Psychology, Inc.

The Multiple Roles of the Task Design Mediator in Telecollaboration

ERIC Educational Resources Information Center

Fuchs, Carolin; Snyder, Bill; Tung, Bruce; Jung Han, Yu

2017-01-01

This case study explores how a Chinese-American novice teacher acted as mediator in a telecollaboration with student teacher (ST) peers in the USA who designed tasks for his English as a foreign language (EFL) learners in China. The novice teacher was instrumental in mediating the student teachers' task design process by providing feedback…

Multiple mediators of the relationships among maternal childhood abuse, intimate partner violence, and offspring psychopathology.

PubMed

Miranda, Jenniffer K; de la Osa, Nuria; Granero, Roser; Ezpeleta, Lourdes

2013-09-01

The aim of the study was to examine whether maternal depression, mothers' and fathers' parenting, child physical punishment and negative life events (NLE) mediate the effect of maternal childhood abuse (CA), intimate partner violence (IPV) and cumulative violence (both CA and IPV) on Spanish children's and adolescents' psychopathology. Furthermore, multiple mediator models examine whether IPV mediates the effect of CA on the contextual and family factors mentioned above. Three hundred and eighteen Spanish outpatients aged 7 to 18 and their parents were assessed using a structured interview and other instruments for measuring the study variables. Structural equation models (SEMs) showed multiple pathways explaining psychopathological problems among offspring of mothers who suffered CA, IPV and both of these violent experiences. In particular, mothers' depression mediated the link between maternal CA, IPV, cumulative violence and children's externalizing, and total behavior problems. Child NLE was an important pathway between maternal CA and total behavior problems, as well as between cumulative violence and both externalizing and total problems. IPV contributed to explaining the link between maternal CA and contextual and family factors, such as child physical punishment and NLE, which were in turn, associated with children's behavior problems. Findings show the complex interconnections between different types of violence and their harmful effects on the mental health of women and their offspring, as well as the need to extend our knowledge on this subject.

Impact of emotional competence on supportive care needs, anxiety and depression symptoms of cancer patients: a multiple mediation model.

PubMed

Baudry, A-S; Lelorain, S; Mahieuxe, M; Christophe, V

2018-01-01

The aim of this study was to test the effect of intrapersonal and interpersonal emotional competence on cancer patients' supportive care needs, as mediated by anxiety and depression symptoms. Cross-sectional design: 137 cancer patients (42% breast or ovarian cancer, 58% gastrointestinal cancer) in 4 French hospitals completed the Profile of Emotional Competence (PEC), the Hospital Anxiety and Depression Scale (HADS), and the Supportive Care Needs Survey Short Form (SCNS-SF). Bootstrap methods with PROCESS Macro were used to test multiple mediation models. Emotional competence presented a direct or indirect beneficial effect on the satisfaction of supportive care needs, anxiety and depression symptoms. As expected, anxiety and depression symptoms had also strong positive correlations with unmet needs. All multiple mediation models were significant, except for physical needs: intrapersonal and interpersonal emotional competence impacted anxiety and depression symptoms, which in turn impacted psychological, sexual, care/support, and information needs. These innovative results show the important effect of patients' emotional competence on their supportive care need satisfaction, as mediated by anxiety and depression. Consequently, patients with high emotional competence may require less psychosocial input from medical clinicians. Thus, emotional competence may be integrated into health models and psychosocial interventions to improve patient adjustment. Further investigation is, however, needed to know which are the most beneficial specific emotional competences and at what point of the cancer pathway.

Ethnic and racial socialization and self-esteem of Asian adoptees: the mediating role of multiple identities.

PubMed

Mohanty, Jayashree

2013-02-01

Positive identity development during adolescence in general is a complex process and may pose additional challenges for adolescents adopted from a different culture. Using a web-based survey design with a sample of 100 internationally adopted Asian adolescent and young adults, the present study examined the mediating role of multiple identities (i.e., ethnic, adoptive and interpersonal ego identities) in explaining the relationship between ethnic and racial socializations, ethnic neighborhood, and self-esteem. The results showed that (a) adoptive identity mediated the influence of racial socialization on psychological well-being, and (b) ethnic affirmation mediated the influence of ethnic socialization on adoptees' well-being. This study illustrates the importance of providing supportive counseling services for adoptees who are exploring their adoptive identity. Copyright © 2012 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

External Criticism by Parents and Obsessive Beliefs in Adolescents: Mediating Role of Beliefs associated with Inflated Responsibility.

PubMed

Halvaiepour, Zohreh; Nosratabadi, Mehdi

2015-09-18

Obsessive-compulsive disorder (OCD) is considered as a rare disorder in children. According to cognitive theories, criticism triggers responsibility behavior and thus causes obsessive behaviors. The purpose of the present study was to investigate the mediating role of beliefs associated with responsibility in the relationship between external criticism of parents and obsessive beliefs in adolescents. In this study, 547 high school students aged from 15 to18 years were selected using multi-stage cluster random sampling from four regions of the education office in Shiraz. Obsessive Beliefs Questionnaire-child version (OBQ-CV), Pathway to Inflated Responsibility beliefs Scale (PIRBS), and perceived criticism questionnaire were used to collect data. Pearson's correlation was used to investigate the relationship between the study variables. For analysis of mediation model, multiple mediators analysis using Macro Software was used. External criticism only indirectly and through beliefs associated with inflated responsibility accounts for 6% of the variance of responsibility, 14% of the variance of threat estimation and 10% of the variance of perfectionism of obsessive beliefs (P<0.05). However, external criticism, both directly and indirectly and through beliefs associated with inflated responsibility accounts for 7% of the variance of the importance of obsessive beliefs. This study showed that the beliefs associated with inflated responsibility can mediate the relationship between external criticism and obsessive beliefs. According to the cognitive model of Salkovskis, criticism by parents, as a violation to and an influence on children, by affecting the subscales of inflated responsibility, can increase the symptoms of obsessive-compulsive disorder. In order to identify potential affecting mechanisms of criticism on obsessive-compulsive disorder, further experimental research is required.

[Role of self-leadership in the relationship between organizational culture and informatics competency].

PubMed

Kim, Myoung Soo

2009-10-01

The purpose of this study was to identify the moderating and mediating effects of self-leadership in the relationship between organizational culture and nurses' informatics competency. Participants in this study were 297 nurses from the cities of Busan and Ulsan. The scales of organizational culture, self-leadership and informatics competency for nurses were used in this study. Descriptive statistics, Pearson correlation coefficient, stepwise multiple regression were used for data analysis. Nursing informatics competency of the participants was relatively low with a mean score 3.02. There were significant positive correlations between subcategories of perceived organizational culture, self-leadership and nursing informatics competency. Self-leadership was a moderator and a mediator between organizational culture and informatics competency. Based on the results of this study, self-leadership promotion strategies to improve nursing informatics competency are needed.

Humin as an electron donor for enhancement of multiple microbial reduction reactions with different redox potentials in a consortium.

PubMed

Zhang, Dongdong; Zhang, Chunfang; Xiao, Zhixing; Suzuki, Daisuke; Katayama, Arata

2015-02-01

A solid-phase humin, acting as an electron donor, was able to enhance multiple reductive biotransformations, including dechlorination of pentachlorophenol (PCP), dissimilatory reduction of amorphous Fe (III) oxide (FeOOH), and reduction of nitrate, in a consortium. Humin that was chemically reduced by NaBH4 served as an electron donor for these microbial reducing reactions, with electron donating capacities of 0.013 mmol e(-)/g for PCP dechlorination, 0.15 mmol e(-)/g for iron reduction, and 0.30 mmol e(-)/g for nitrate reduction. Two pairs of oxidation and reduction peaks within the humin were detected by cyclic voltammetry analysis. 16S rRNA gene sequencing-based microbial community analysis of the consortium incubated with different terminal electron acceptors, suggested that Dehalobacter sp., Bacteroides sp., and Sulfurospirillum sp. were involved in the PCP dechlorination, dissimilatory iron reduction, and nitrate reduction, respectively. These findings suggested that humin functioned as a versatile redox mediator, donating electrons for multiple respiration reactions with different redox potentials. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Multiple Sclerosis: Associations Between Physical Disability and Depression Are Not Mediated by Self-Reported Physical Activity.

PubMed

Sadeghi Bahmani, Dena; Calabrese, Pasquale; Merkt, Helene; Naegelin, Yvonne; Gerber, Markus; Pühse, Uwe; Holsboer-Trachsler, Edith; Brand, Serge

2017-10-01

This study investigated the interrelatedness of physical disability, physical activity, and depression among patients with multiple sclerosis (MS). We hypothesized that self-reported physical activity would mediate the effect of disability on depressive symptoms. Twenty-seven patients with MS (mean age: 49 years; 44.5% females) completed self-rating scales covering sociodemographic variables, intake of antidepressants, physical activity, and symptoms of depression; disability was measured by the Expanded Disability Status Scale. We found a higher level of disability to be significantly associated with more symptoms of depression. While higher reported physical activity was descriptively associated with lower depression scores and unrelated to Expanded Disability Status Scale, physical activity levels did not mediate the effect of disability on depressive symptoms.

Identifying the Average Causal Mediation Effects with Multiple Mediators in the Presence of Treatment Non-Compliance

ERIC Educational Resources Information Center

Park, Soojin

2015-01-01

Identifying the causal mechanisms is becoming more essential in social and medical sciences. In the presence of treatment non-compliance, the Intent-To-Treated effect (hereafter, ITT effect) is identified as long as the treatment is randomized (Angrist et al., 1996). However, the mediated portion of effect is not identified without additional…

Mediating Effects of Social Support on Quality of Life for Parents of Adults with Autism

ERIC Educational Resources Information Center

Marsack, Christina N.; Samuel, Preethy S.

2017-01-01

The aim of this study was to examine the mediating effect of formal and informal social support on the relationship of caregiver burden and quality of life (QOL), using a sample of 320 parents (aged 50 or older) of adult children with autism spectrum disorder (ASD). Multiple linear regression and mediation analyses indicated that caregiver burden…

Quality of Life as a Mediator between Behavioral Challenges and Autistic Traits for Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Garcia-Villamisar, Domingo; Dattilo, John; Matson, Johnny L.

2013-01-01

A multiple mediation model was proposed to integrate core concepts of challenging behaviors with autistic traits to increase understanding of their relationship to quality of life (QoL). It was hypothesized that QoL is a possible mediator between the severity of challenging behaviors and autistic traits in adults with intellectual disability.…

Perceived Interpersonal Burdensomeness as a Mediator between Nightmare Distress and Suicidal Ideation in Nightmare Sufferers

PubMed Central

Suh, Sooyeon; Schneider, Matthew; Lee, Ruda; Joiner, Thomas

2016-01-01

Previous studies have supported the significant association between nightmares and suicidal ideation, but the underlying mechanisms are largely unknown. The purpose of the present study was to investigate perceived burdensomeness and thwarted belongingness as mediators in the relationship between nightmare distress and suicidal ideation. This sample consisted of 301 undergraduate students who endorsed experiencing nightmares (mean age 21.87 ± 2.17, 78.1% female). All participants completed questionnaires on nightmare distress (Nightmare Distress Questionnaire), unmet interpersonal needs (Interpersonal Needs Questionnaire), and suicidal ideation (Depressive Symptom Inventory – Suicidality Subscale). Analyses were performed using multiple mediation regression. Results indicated that nightmare distress was associated with perceived burdensomeness (r = 0.17, p < 0.001) and suicidal ideation (r = 0.24, p < 0.001), but was not related to thwarted belongingness (r = 0.10, p = 0.06). Multiple mediation analyses revealed that perceived burdensomeness partially mediated the relationship between nightmares and suicidal ideation, but thwarted belongingness did not. Additionally, this mediating relationship for perceived burdensomeness was moderated by gender, being significant only for females. These findings highlight the important role of interpersonal factors in the relationship between nightmares and suicidal ideation. PMID:27917142

Sensory mediation of stimulus-driven attentional capture in multiple-cue displays.

PubMed

Wright, Richard D; Richard, Christian M

2003-08-01

Three location-cuing experiments were conducted in order to examine the stimulus-driven control of attentional capture in multiple-cue displays. These displays consisted of one to four simultaneously presented direct location cues. The results indicated that direct location cuing can produce cue effects that are mediated, in part, by nonattentional processing that occurs simultaneously at multiple locations. When single cues were presented in isolation, however, the resulting cue effect appeared to be due to a combination of sensory processing and attentional capture by the cue. This suggests that the faster responses produced by direct cues may be associated with two different components: an attention-related component that can be modulated by goal-driven factors and a nonattentional component that occurs in parallel at multiple direct-cue locations and is minimally affected by goal-driven factors.

Metabolomic Modularity Analysis (MMA) to Quantify Human Liver Perfusion Dynamics.

PubMed

Sridharan, Gautham Vivek; Bruinsma, Bote Gosse; Bale, Shyam Sundhar; Swaminathan, Anandh; Saeidi, Nima; Yarmush, Martin L; Uygun, Korkut

2017-11-13

Large-scale -omics data are now ubiquitously utilized to capture and interpret global responses to perturbations in biological systems, such as the impact of disease states on cells, tissues, and whole organs. Metabolomics data, in particular, are difficult to interpret for providing physiological insight because predefined biochemical pathways used for analysis are inherently biased and fail to capture more complex network interactions that span multiple canonical pathways. In this study, we introduce a nov-el approach coined Metabolomic Modularity Analysis (MMA) as a graph-based algorithm to systematically identify metabolic modules of reactions enriched with metabolites flagged to be statistically significant. A defining feature of the algorithm is its ability to determine modularity that highlights interactions between reactions mediated by the production and consumption of cofactors and other hub metabolites. As a case study, we evaluated the metabolic dynamics of discarded human livers using time-course metabolomics data and MMA to identify modules that explain the observed physiological changes leading to liver recovery during subnormothermic machine perfusion (SNMP). MMA was performed on a large scale liver-specific human metabolic network that was weighted based on metabolomics data and identified cofactor-mediated modules that would not have been discovered by traditional metabolic pathway analyses.

Programmable and multiparameter DNA-based logic platform for cancer recognition and targeted therapy.

PubMed

You, Mingxu; Zhu, Guizhi; Chen, Tao; Donovan, Michael J; Tan, Weihong

2015-01-21

The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention. With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable. As a trial to accomplish this, we have recently designed a DNA-based device that is capable of performing autonomous logic-based analysis of two or three cancer cell-surface markers. Combining the specific target-recognition properties of DNA aptamers with toehold-mediated strand displacement reactions, multicellular marker-based cancer analysis can be realized based on modular AND, OR, and NOT Boolean logic gates. Specifically, we report here a general approach for assembling these modular logic gates to execute programmable and higher-order profiling of multiple coexisting cell-surface markers, including several found on cancer cells, with the capacity to report a diagnostic signal and/or deliver targeted photodynamic therapy. The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy.

Quantitative analysis of multiple sclerosis: a feasibility study

NASA Astrophysics Data System (ADS)

Li, Lihong; Li, Xiang; Wei, Xinzhou; Sturm, Deborah; Lu, Hongbing; Liang, Zhengrong

2006-03-01

Multiple Sclerosis (MS) is an inflammatory and demyelinating disorder of the central nervous system with a presumed immune-mediated etiology. For treatment of MS, the measurements of white matter (WM), gray matter (GM), and cerebral spinal fluid (CSF) are often used in conjunction with clinical evaluation to provide a more objective measure of MS burden. In this paper, we apply a new unifying automatic mixture-based algorithm for segmentation of brain tissues to quantitatively analyze MS. The method takes into account the following effects that commonly appear in MR imaging: 1) The MR data is modeled as a stochastic process with an inherent inhomogeneity effect of smoothly varying intensity; 2) A new partial volume (PV) model is built in establishing the maximum a posterior (MAP) segmentation scheme; 3) Noise artifacts are minimized by a priori Markov random field (MRF) penalty indicating neighborhood correlation from tissue mixture. The volumes of brain tissues (WM, GM) and CSF are extracted from the mixture-based segmentation. Experimental results of feasibility studies on quantitative analysis of MS are presented.

Molecular architecture of the human Mediator-RNA polymerase II-TFIIF assembly.

PubMed

Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C; Nogales, Eva; Taatjes, Dylan J

2011-03-01

The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator-pol II interface is not well-characterized, whereas attempts to structurally define the Mediator-pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator-pol II-TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator-pol II-TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator-pol II-TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator-CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator-pol II complexes lacking TFIIF reveal that TFIIF plays a key role in stabilizing pol II orientation within the assembly.

Mediation of the Relationship Between Callous-Unemotional Traits and Proactive Aggression by Amygdala Response to Fear Among Children With Conduct Problems

PubMed Central

Lozier, Leah M.; Cardinale, Elise M.; VanMeter, John W.; Marsh, Abigail A.

2015-01-01

Importance Among youths with conduct problems, callous-unemotional (CU) traits are known to be an important determinant of symptom severity, prognosis, and treatment responsiveness. But positive correlations between conduct problems and CU traits result in suppressor effects that may mask important neurobiological distinctions among subgroups of children with conduct problems. Objective To assess the unique neurobiological covariates of CU traits and externalizing behaviors in youths with conduct problems and determine whether neural dysfunction linked to CU traits mediates the link between callousness and proactive aggression. Design, Setting, and Participants This cross-sectional case-control study involved behavioral testing and neuroimaging that were conducted at a university research institution. Neuroimaging was conducted using a 3-T Siemens magnetic resonance imaging scanner. It included 46 community-recruited male and female juveniles aged 10 to 17 years, including 16 healthy control participants and 30 youths with conduct problems with both low and high levels of CU traits. Main Outcomes and Measures Blood oxygenation level–dependent signal as measured via functional magnetic resonance imaging during an implicit face-emotion processing task and analyzed using whole-brain and region of interest–based analysis of variance and multiple-regression analyses. Results Analysis of variance revealed no group differences in the amygdala. By contrast, consistent with the existence of suppressor effects, multiple-regression analysis found amygdala responses to fearful expressions to be negatively associated with CU traits (x = 26, y = 0, z = −12; k = 1) and positively associated with externalizing behavior (x = 24, y = 0, z = −14; k = 8) when both variables were modeled simultaneously. Reduced amygdala responses mediated the relationship between CU traits and proactive aggression. Conclusions and Relevance The results linked proactive aggression in youths with CU traits to hypoactive amygdala responses to emotional distress cues, consistent with theories that externalizing behaviors, particularly proactive aggression, in youths with these traits stem from deficient empathic responses to distress. Amygdala hypoactivity may represent an intermediate phenotype, offering new insights into effective treatment strategies for conduct problems. PMID:24671141

Insecticide resistance is mediated by multiple mechanisms in recently introduced Aedes aegypti from Madeira Island (Portugal).

PubMed

Seixas, Gonçalo; Grigoraki, Linda; Weetman, David; Vicente, José Luís; Silva, Ana Clara; Pinto, João; Vontas, John; Sousa, Carla Alexandra

2017-07-01

Aedes aegypti is a major mosquito vector of arboviruses, including dengue, chikungunya and Zika. In 2005, Ae. aegypti was identified for the first time in Madeira Island. Despite an initial insecticide-based vector control program, the species expanded throughout the Southern coast of the island, suggesting the presence of insecticide resistance. Here, we characterized the insecticide resistance status and the underlying mechanisms of two populations of Ae. aegypti from Madeira Island, Funchal and Paúl do Mar. WHO susceptibility bioassays indicated resistance to cyfluthrin, permethrin, fenitrothion and bendiocarb. Use of synergists significantly increased mortality rates, and biochemical assays indicated elevated activities of detoxification enzymes, suggesting the importance of metabolic resistance. Microarray-based transcriptome analysis detected significant upregulation in both populations of nine cytochrome P450 oxidase genes (including four known pyrethroid metabolizing enzymes), the organophosphate metabolizer CCEae3a, Glutathione-S-transferases, and multiple putative cuticle proteins. Genotyping of knockdown resistance loci linked to pyrethroid resistance revealed fixation of the 1534C mutation, and presence with moderate frequencies of the V1016I mutation in each population. Significant resistance to three major insecticide classes (pyrethroid, carbamate and organophosphate) is present in Ae. aegypti from Madeira Island, and appears to be mediated by multiple mechanisms. Implementation of appropriate resistance management strategies including rotation of insecticides with alternative modes of action, and methods other than chemical-based vector control are strongly advised to delay or reverse the spread of resistance and achieve efficient control.

Testing Cross-Sectional and Prospective Mediators of Internalized Heterosexism on Heavy Drinking, Alcohol Problems, and Psychological Distress Among Heavy Drinking Men Who Have Sex With Men.

PubMed

Kuerbis, Alexis; Mereish, Ethan H; Hayes, Marie; Davis, Christine M; Shao, Sijing; Morgenstern, Jon

2017-01-01

Minority stress theory is one of the primary theories used to understand substance use among lesbian, gay, and bisexual populations. This study tested whether drinking to cope with stress (DTC), loneliness, and gay community participation (GCP) mediated the relationship between one type of minority stress (i.e., internalized heterosexism) and behavioral health outcomes. Using secondary data analysis and the PROCESS procedure, relationships between internalized heterosexism, the mediators (DTC, loneliness, and GCP), and outcomes (heavy drinking, alcohol problems, and psychological distress) were explored, both cross-sectionally and in a lagged manner, among both treatment-seeking and non-treatment-seeking problem drinking men who have sex with men. Problem drinkers (N = 187) were assessed, provided brief normative feedback about their drinking, given the choice to receive brief alcohol use disorder treatment or change on their own, and then followed for 9 months. Cross-sectional findings revealed that internalized heterosexism was significantly associated with heavy drinking, alcohol problems, and psychological distress. DTC emerged as a significant mediator of internalized heterosexism for all the health outcomes. Loneliness and GCP were significant mediators of internalized heterosexism for alcohol problems and psychological distress. Multiple mediation models reveal that all three mediators significantly contribute to internalized heterosexism's effect on health outcomes. Lagged analyses did not yield any significant indirect effects. DTC, loneliness, and GCP all play an integral, mediational role in the relationship between internalized heterosexism and alcohol problems and psychological distress. Findings underscore the necessity of addressing internalized heterosexism in psychosocial interventions along with coping skills training, emphasizing culturally relevant social support and loneliness.

Associations of Organizational Justice with Tinnitus and the Mediating Role of Depressive Symptoms and Burnout-Findings from a Cross-Sectional Study.

PubMed

Herr, Raphael M; Loerbroks, Adrian; Bosch, Jos A; Seegel, Max; Schneider, Michael; Schmidt, Burkhard

2016-04-01

Tinnitus refers to the perception of a sound while an external source is absent. Research has identified work-related stress and its potential mental health-related sequelaes, i.e., depression and burnout, as risk factors for tinnitus. Perceived unfairness at work (organizational injustice), which is considered a psychosocial occupational stressor, has been shown to predict depression and burnout but its potential associations with tinnitus remains unaddressed. The aim was to determine the relationship of organizational injustice with tinnitus, and to examine depression and burnout as potential mediators. Cross-sectional data from a sample of 1632 employees were used. Tinnitus was assessed by self-report (n = 207; 13.9 %). Organizational justice and its subcomponents (interactional and procedural justice), burnout, and depressive symptoms were measured by validated questionnaires. Associations were assessed by logistic regressions, and mediation was assessed by maximum likelihood logistic regression estimations. Overall organizational justice, interactional and procedural justice were inversely related to tinnitus (z-score for overall justice: OR = 0.754; 95 % CI = 0.649 to 0.876). These associations were independent of demographics, socioeconomic status, job characteristics (including potential noise exposure), and health behaviors. Mediation analyses suggested a potential mediation by burnout (95 % CI indirect effect -0.188 to -0.066) and depressive symptoms (95 % CI indirect effect -0.160 to -0.043). Parallel multiple mediation analysis revealed that mediation through burnout was significantly larger than through depressive symptoms. Organizational justice appeared inversely related to tinnitus and this association was explained by individual differences in burnout symptoms, suggesting mediation. Longitudinal studies may further help to strengthen the evidence base for prevention of tinnitus through promotion of organizational justice and prevention of burnout.

Silencing SlMED18, tomato Mediator subunit 18 gene, restricts internode elongation and leaf expansion.

PubMed

Wang, Yunshu; Hu, Zongli; Zhang, Jianling; Yu, XiaoHui; Guo, Jun-E; Liang, Honglian; Liao, Changguang; Chen, Guoping

2018-02-19

Mediator complex, a conserved multi-protein, is necessary for controlling RNA polymerase II (Pol II) transcription in eukaryotes. Given little is known about them in tomato, a tomato Mediator subunit 18 gene was isolated and named SlMED18. To further explore the function of SlMED18, the transgenic tomato plants targeting SlMED18 by RNAi-mediated gene silencing were generated. The SlMED18-RNAi lines exhibited multiple developmental defects, including smaller size and slower growth rate of plant and significantly smaller compound leaves. The contents of endogenous bioactive GA 3 in SlMED18 silenced lines were slightly less than that in wild type. Furthermore, qRT-PCR analysis indicated that expression of gibberellins biosynthesis genes such as SlGACPS and SlGA20x2, auxin transport genes (PIN1, PIN4, LAX1 and LAX2) and several key regulators, KNOX1, KNOX2, PHAN and LANCEOLATE(LA), which involved in the leaf morphogenesis were significantly down-regulated in SlMED18-RNAi lines. These results illustrated that SlMED18 plays an essential role in regulating plant internode elongation and leaf expansion in tomato plants and it acts as a key positive regulator of gibberellins biosynthesis and signal transduction as well as auxin proper transport signalling. These findings are the basis for understanding the function of the individual Mediator subunits in tomato.

Identification of aberrant gene expression associated with aberrant promoter methylation in primordial germ cells between E13 and E16 rat F3 generation vinclozolin lineage.

PubMed

Taguchi, Y-h

2015-01-01

Transgenerational epigenetics (TGE) are currently considered important in disease, but the mechanisms involved are not yet fully understood. TGE abnormalities expected to cause disease are likely to be initiated during development and to be mediated by aberrant gene expression associated with aberrant promoter methylation that is heritable between generations. However, because methylation is removed and then re-established during development, it is not easy to identify promoter methylation abnormalities by comparing normal lineages with those expected to exhibit TGE abnormalities. This study applied the recently proposed principal component analysis (PCA)-based unsupervised feature extraction to previously reported and publically available gene expression/promoter methylation profiles of rat primordial germ cells, between E13 and E16 of the F3 generation vinclozolin lineage that are expected to exhibit TGE abnormalities, to identify multiple genes that exhibited aberrant gene expression/promoter methylation during development. The biological feasibility of the identified genes were tested via enrichment analyses of various biological concepts including pathway analysis, gene ontology terms and protein-protein interactions. All validations suggested superiority of the proposed method over three conventional and popular supervised methods that employed t test, limma and significance analysis of microarrays, respectively. The identified genes were globally related to tumors, the prostate, kidney, testis and the immune system and were previously reported to be related to various diseases caused by TGE. Among the genes reported by PCA-based unsupervised feature extraction, we propose that chemokine signaling pathways and leucine rich repeat proteins are key factors that initiate transgenerational epigenetic-mediated diseases, because multiple genes included in these two categories were identified in this study.

Identification of aberrant gene expression associated with aberrant promoter methylation in primordial germ cells between E13 and E16 rat F3 generation vinclozolin lineage

PubMed Central

2015-01-01

Background Transgenerational epigenetics (TGE) are currently considered important in disease, but the mechanisms involved are not yet fully understood. TGE abnormalities expected to cause disease are likely to be initiated during development and to be mediated by aberrant gene expression associated with aberrant promoter methylation that is heritable between generations. However, because methylation is removed and then re-established during development, it is not easy to identify promoter methylation abnormalities by comparing normal lineages with those expected to exhibit TGE abnormalities. Methods This study applied the recently proposed principal component analysis (PCA)-based unsupervised feature extraction to previously reported and publically available gene expression/promoter methylation profiles of rat primordial germ cells, between E13 and E16 of the F3 generation vinclozolin lineage that are expected to exhibit TGE abnormalities, to identify multiple genes that exhibited aberrant gene expression/promoter methylation during development. Results The biological feasibility of the identified genes were tested via enrichment analyses of various biological concepts including pathway analysis, gene ontology terms and protein-protein interactions. All validations suggested superiority of the proposed method over three conventional and popular supervised methods that employed t test, limma and significance analysis of microarrays, respectively. The identified genes were globally related to tumors, the prostate, kidney, testis and the immune system and were previously reported to be related to various diseases caused by TGE. Conclusions Among the genes reported by PCA-based unsupervised feature extraction, we propose that chemokine signaling pathways and leucine rich repeat proteins are key factors that initiate transgenerational epigenetic-mediated diseases, because multiple genes included in these two categories were identified in this study. PMID:26677731

A systems biology approach to the analysis of subset-specific responses to lipopolysaccharide in dendritic cells.

PubMed

Hancock, David G; Shklovskaya, Elena; Guy, Thomas V; Falsafi, Reza; Fjell, Chris D; Ritchie, William; Hancock, Robert E W; Fazekas de St Groth, Barbara

2014-01-01

Dendritic cells (DCs) are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 commitment, generating inducible Tregs, and mediating tolerance. It is believed that distinct DC subsets have evolved to control these different immune outcomes. However, how DC subsets mount different responses to inflammatory and/or tolerogenic signals in order to accomplish their divergent functions remains unclear. Lipopolysaccharide (LPS) provides an excellent model for investigating responses in closely related splenic DC subsets, as all subsets express the LPS receptor TLR4 and respond to LPS in vitro. However, previous studies of the LPS-induced DC transcriptome have been performed only on mixed DC populations. Moreover, comparisons of the in vivo response of two closely related DC subsets to LPS stimulation have not been reported in the literature to date. We compared the transcriptomes of murine splenic CD8 and CD11b DC subsets after in vivo LPS stimulation, using RNA-Seq and systems biology approaches. We identified subset-specific gene signatures, which included multiple functional immune mediators unique to each subset. To explain the observed subset-specific differences, we used a network analysis approach. While both DC subsets used a conserved set of transcription factors and major signalling pathways, the subsets showed differential regulation of sets of genes that 'fine-tune' the network Hubs expressed in common. We propose a model in which signalling through common pathway components is 'fine-tuned' by transcriptional control of subset-specific modulators, thus allowing for distinct functional outcomes in closely related DC subsets. We extend this analysis to comparable datasets from the literature and confirm that our model can account for cell subset-specific responses to LPS stimulation in multiple subpopulations in mouse and man.

Reciprocal effects among changes in weight, body image, and other psychological factors during behavioral obesity treatment: a mediation analysis.

PubMed

Palmeira, António L; Markland, David A; Silva, Marlene N; Branco, Teresa L; Martins, Sandra C; Minderico, Cláudia S; Vieira, Paulo N; Barata, José T; Serpa, Sidónio O; Sardinha, Luis B; Teixeira, Pedro J

2009-02-09

Changes in body image and subjective well-being variables (e.g. self-esteem) are often reported as outcomes of obesity treatment. However, they may, in turn, also influence behavioral adherence and success in weight loss. The present study examined associations among obesity treatment-related variables, i.e., change in weight, quality of life, body image, and subjective well-being, exploring their role as both mediators and outcomes, during a behavioral obesity treatment. Participants (BMI = 31.1 +/- 4.1 kg/m2; age = 38.4 +/- 6.7 y) were 144 women who attended a 12-month obesity treatment program and a comparison group (n = 49), who received a general health education program. The intervention included regular group meetings promoting lasting behavior changes in physical activity and dietary intake. Body image, quality of life, subjective well-being, and body weight were measured at baseline and treatment's end. Mediation was tested by multiple regression and a resampling approach to measure indirect effects. Treatment group assignment was the independent variable while changes in weight and in psychosocial variables were analyzed alternatively as mediators and as dependent variables. At 12 months, the intervention group had greater weight loss (-5.6 +/- 6.8% vs. -1.2 +/- 4.6%, p < .001) and larger decreases in body size dissatisfaction (effect size of 1.08 vs. .41, p < .001) than the comparison group. Significant improvements were observed in both groups for all other psychosocial variables (effect sizes ranging from .31-.75, p < .05). Mediation analysis showed that changes in body image and body weight were concurrently mediators and outcomes of treatment, suggesting reciprocal influences. Weight loss partially mediated the effect of treatment on quality of life and on self-esteem but the reciprocal effect was not observed. Changes in weight and body image may reciprocally affect each other during the course of behavioral obesity treatment. No evidence of reciprocal relationships was found for the other models under analysis; however, weight changes partially explained the effects of treatment on quality of life and self-esteem. Weight and psychosocial changes co-occur during treatment and will probably influence each other dynamically, in ways not yet adequately understood. Results from this study support the inclusion of intervention contents aimed at improving body image in weight management programs.

Mechanism evaluation of a lifestyle intervention for patients with musculoskeletal pain who are overweight or obese: protocol for a causal mediation analysis.

PubMed

Lee, Hopin; Wiggers, John; Kamper, Steven J; Williams, Amanda; O'Brien, Kate M; Hodder, Rebecca K; Wolfenden, Luke; Yoong, Sze Lin; Campbell, Elizabeth; Haskins, Robin; Robson, Emma K; McAuley, James H; Williams, Christopher M

2017-07-03

Low back pain (LBP) and knee osteoarthritis (OA) are highly prevalent and disabling conditions that cause societal and economic impact worldwide. Two randomised controlled trials (RCTs) will evaluate the effectiveness of a multicomponent lifestyle intervention for patients with LBP and knee OA who are overweight or obese. The key targets of this intervention are to improve physical activity, modify diet and correct pain beliefs. These factors may explain how a lifestyle intervention exerts its effects on key patient-relevant outcomes: pain, disability and quality of life. The aim of this protocol is to describe a planned analysis of a mechanism evaluation for a lifestyle intervention for overweight or obese patients with LBP and knee OA. Causal mediation analyses of 2 two-armed RCTs. Both trials are part of a cohort-multiple RCT, embedded in routine health service delivery. In each respective trial, 160 patients with LBP and 120 patients with knee OA waiting for orthopaedic consultation will be randomised to a lifestyle intervention, or to remain part of the original cohort. The intervention consists of education and advice about the benefits of weight loss and physical activity, and the Australian New South Wales Get Healthy Service. All outcome measures including patient characteristics, primary and alternative mediators, outcomes, and potential confounders will be measured at baseline (T0). The primary mediator, weight, will be measured at 6 months post randomisation; alternative mediators including diet, physical activity and pain beliefs will be measured at 6 weeks post randomisation. All outcomes (pain, disability and quality of life) will be measured at 6 months post randomisation. Data will be analysed using causal mediation analysis with sensitivity analyses for sequential ignorability. All mediation models were specified a priori before completing data collection and without prior knowledge about the effectiveness of the intervention. The study is approved by the Hunter New England Health Human Research Ethics Committee (13/12/11/5.18) and the University of Newcastle Human Research Ethics Committee (H-2015-0043). The results will be disseminated in peer-reviewed journals and at scientific conferences. ACTRN12615000490572 and ACTRN12615000478516; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The impact of self-efficacy, alexithymia and multiple traumas on posttraumatic stress disorder and psychiatric co-morbidity following epileptic seizures: a moderated mediation analysis.

PubMed

Chung, Man Cheung; Allen, Rachel D; Dennis, Ian

2013-12-30

This study investigated the incidence of posttraumatic stress disorder (PTSD) and psychiatric co-morbidity following epileptic seizure, whether alexithymia mediated the relationship between self-efficacy and psychiatric outcomes, and whether the mediational effect was moderated by the severity of PTSD from other traumas. Seventy-one (M=31, F=40) people with a diagnosis of epilepsy recruited from support groups in the United Kingdom completed the Posttraumatic Stress Diagnostic Scale, the Hospital Anxiety and Depression Scale, the Toronto Alexithymia Scale-20 and the Generalized Self-Efficacy Scale. They were compared with 71 people (M=29, F=42) without epilepsy. For people with epilepsy, 51% and 22% met the diagnostic criteria for post-epileptic seizure PTSD and for PTSD following one other traumatic life event respectively. For the control group, 24% met the diagnostic criteria for PTSD following other traumatic life events. The epilepsy group reported significantly more anxiety and depression than the control. Partial least squares (PLS) analysis showed that self-efficacy was significantly correlated with alexithymia, post-epileptic seizure PTSD and psychiatric co-morbidity. Alexithymia was also significantly correlated with post-epileptic seizure PTSD and psychiatric co-morbidity. Mediation analyses confirmed that alexithymia mediated the path between self-efficacy and post-epileptic seizure PTSD and psychiatric co-morbidity. Moderated mediation also confirmed that self-efficacy and PTSD from one other trauma moderated the effect of alexithymia on outcomes. To conclude, people can develop posttraumatic stress disorder symptoms and psychiatric co-morbidity following epileptic seizure. These psychiatric outcomes are closely linked with their belief in personal competence to deal with stressful situations and regulate their own functioning, to process rather than defend against distressing emotions, and with the degree of PTSD from other traumas. © 2013 Elsevier Ireland Ltd. All rights reserved.

Social Anxiety and Heavy Situational Drinking: Coping and Conformity Motives as Multiple Mediators

PubMed Central

Terlecki, Meredith A.; Buckner, Julia D.

2014-01-01

Individuals with clinically elevated social anxiety are at greater risk for alcohol use disorder, and the relation between social anxiety and drinking problems is at least partially accounted for by drinking more in negative emotional (e.g., feeling sad or angry) and personal/intimate (e.g., before sexual intercourse) situations. Identification of cognitive/motivational factors related to drinking in these high-risk situations could inform the development of treatment and prevention interventions for these high-risk drinkers. The current study examined the mediating effect of drinking motives on the relationship between social anxiety and drinking these high-risk situations amongst undergraduates (N = 232). Clinically elevated social anxiety was associated with greater coping and conformity motives. Both coping and conformity motives mediated the relation between social anxiety and heavier alcohol consumption in negative emotional and personal/intimate contexts. Multiple mediation analyses indicated that these motives work additively to mediate the social anxiety-drinking situations relationship, such that that heavy situational drinking amongst undergraduates with clinically elevated social anxiety can be jointly attributed to desire to cope with negative affect and to avoid social scrutiny. PMID:25233446

Multiple transcriptional regulatory domains in the human immunodeficiency virus type 1 long terminal repeat are involved in basal and E1A/E1B-induced promoter activity.

PubMed Central

Kliewer, S; Garcia, J; Pearson, L; Soultanakis, E; Dasgupta, A; Gaynor, R

1989-01-01

The human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR) is the site of activation of the HIV tat protein. However, additional transactivators, such as the adenovirus E1A and herpesvirus ICPO proteins, have also been shown to be capable of activating the HIV LTR. Analysis of adenovirus mutants indicated that complete transactivation of the HIV LTR was dependent on both the E1A and E1B proteins. To determine which regions of the HIV LTR were important for complete E1A/E1B activation, a variety of oligonucleotide-directed mutations in HIV transcriptional regulatory domains were assayed both in vivo and in vitro. S1 nuclease analysis of RNA prepared after transfection of these HIV constructs into HeLa cells infected with wild-type adenovirus indicated that the enhancer, SP1, TATA, and a portion of the transactivation-responsive element were each required for complete E1A/E1B-mediated activation of the HIV LTR. These same promoter elements were required for both basal and E1A/E1B-induced levels of transcription in in vitro transcription reactions performed with cellular extracts prepared from cells infected with dl434, an E1A/E1B deletion mutant, or wild-type adenovirus. No mutations were found that reduced only E1A/E1B-induced expression without proportionally reducing basal levels of transcription, suggesting that E1A/E1B-mediated induction of the HIV LTR requires multiple promoter elements which are also required for basal transcriptional levels. Unlike activation by the tat protein, there was not a rigid dependence on maintenance of the transactivation-responsive stem base pairing for E1A/E1B-mediated activation either in vivo or in vitro, indicating that activation occurs by a mechanism distinct from that of tat induction. Images PMID:2529378

What carries a mediation process? Configural analysis of mediation.

PubMed

von Eye, Alexander; Mun, Eun Young; Mair, Patrick

2009-09-01

Mediation is a process that links a predictor and a criterion via a mediator variable. Mediation can be full or partial. This well-established definition operates at the level of variables even if they are categorical. In this article, two new approaches to the analysis of mediation are proposed. Both of these approaches focus on the analysis of categorical variables. The first involves mediation analysis at the level of configurations instead of variables. Thus, mediation can be incorporated into the arsenal of methods of analysis for person-oriented research. Second, it is proposed that Configural Frequency Analysis (CFA) can be used for both exploration and confirmation of mediation relationships among categorical variables. The implications of using CFA are first that mediation hypotheses can be tested at the level of individual configurations instead of variables. Second, this approach leaves the door open for different types of mediation processes to exist within the same set. Using a data example, it is illustrated that aggregate-level analysis can overlook mediation processes that operate at the level of individual configurations.

Associations between trait emotional intelligence and loneliness in Chinese undergraduate students: mediating effects of self-esteem and social support.

PubMed

Zou, Jilin

2014-06-01

Prior studies indicate that trait emotional intelligence (EI) is associated negatively with loneliness. However, the mechanisms underlying the relationship are not clear. This study assessed whether both self-esteem and social support mediated the associations between trait EI and loneliness. 469 Chinese undergraduate participants whose age ranged from 18 to 23 years (208 women) were asked to complete four self-report questionnaires, including the Wong Law Emotional Intelligence Scale, the Social and Emotional Loneliness Scale, the Rosenberg Self-esteem Scale, and the Multi-Dimensional Scale of Perceived Social Support. Analyses indicated that self-esteem and social support fully mediated the associations between trait EI and loneliness. Effect contrasts indicated that the specific indirect effect through social support was significantly greater than that through self-esteem. Moreover, a multiple-group analysis indicated that no path differed significantly by sex. These results suggest that social support is more important than self-esteem in the association between trait EI and loneliness. Furthermore, both sexes appear to share the same mechanism underlying this association.

Stress as a mediator between work-family conflict and psychological health among the nursing staff: Moderating role of emotional intelligence.

PubMed

Sharma, Jyoti; Dhar, Rajib Lochan; Tyagi, Akansha

2016-05-01

The study examined the extent to which work-family conflicts cause stress among nursing staff and its subsequent impact on their psychological health. It also examined if the emotional intelligence level of the nursing staff acted as a moderator between their level of stress and psychological health. A survey was carried out on 693 nursing staff associated with 33 healthcare institutions in Uttarakhand, India. A hierarchical multiple regression analysis was carried out to understand the relationships shared by independent (work-family conflicts) and dependent (psychological health) constructs with the mediator (stress) as well as the moderator (emotional intelligence). The results revealed that stress acted as a mediator between work-family conflict of the nursing staff and their psychological health. However, their emotional intelligence level acted as a moderator between their stress level and psychological health. To conclude, the crucial roles of emotional intelligence in controlling the impact of stress on psychological health along with the practical as well as theoretical implications are also discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Autonomous and controlled motivational regulations for multiple health-related behaviors: between- and within-participants analyses

PubMed Central

Hagger, M.S.; Hardcastle, S.J.; Chater, A.; Mallett, C.; Pal, S.; Chatzisarantis, N.L.D.

2014-01-01

Self-determination theory has been applied to the prediction of a number of health-related behaviors with self-determined or autonomous forms of motivation generally more effective in predicting health behavior than non-self-determined or controlled forms. Research has been confined to examining the motivational predictors in single health behaviors rather than comparing effects across multiple behaviors. The present study addressed this gap in the literature by testing the relative contribution of autonomous and controlling motivation to the prediction of a large number of health-related behaviors, and examining individual differences in self-determined motivation as a moderator of the effects of autonomous and controlling motivation on health behavior. Participants were undergraduate students (N = 140) who completed measures of autonomous and controlled motivational regulations and behavioral intention for 20 health-related behaviors at an initial occasion with follow-up behavioral measures taken four weeks later. Path analysis was used to test a process model for each behavior in which motivational regulations predicted behavior mediated by intentions. Some minor idiosyncratic findings aside, between-participants analyses revealed significant effects for autonomous motivational regulations on intentions and behavior across the 20 behaviors. Effects for controlled motivation on intentions and behavior were relatively modest by comparison. Intentions mediated the effect of autonomous motivation on behavior. Within-participants analyses were used to segregate the sample into individuals who based their intentions on autonomous motivation (autonomy-oriented) and controlled motivation (control-oriented). Replicating the between-participants path analyses for the process model in the autonomy- and control-oriented samples did not alter the relative effects of the motivational orientations on intention and behavior. Results provide evidence for consistent effects of autonomous motivation on intentions and behavior across multiple health-related behaviors with little evidence of moderation by individual differences. Findings have implications for the generalizability of proposed effects in self-determination theory and intentions as a mediator of distal motivational factors on health-related behavior. PMID:25750803

The Interplay among BMI z-Score, Peer Victmization, and Self-Concept in Outpatient Children and Adolescents with Overweight or Obesity.

PubMed

Bacchini, Dario; Licenziati, Maria Rosaria; Affuso, Gaetana; Garrasi, Alessandra; Corciulo, Nicola; Driul, Daniela; Tanas, Rita; Fiumani, Perla Maria; Di Pietro, Elena; Pesce, Sabino; Crinò, Antonino; Maltoni, Giulio; Iughetti, Lorenzo; Sartorio, Alessandro; Deiana, Manuela; Lombardi, Francesca; Valerio, Giuliana

2017-06-01

Research has provided evidence that obesity is associated with peer victimization and low levels of self-concept. No study has examined the relationship between BMI z-score, self-concept in multiple domains, and peer victimization. The aim of the research was to investigate the interplay between BMI z-score, self-concept in multiple domains (physical, athletic, social), and peer victimization, testing direct, mediated, and moderated associations. Eighty hundred fifteen outpatient children and adolescents were consecutively recruited in 14 hospitals distributed over the Italian country. The sample consisted of 419 males and 396 females; mean age 10.91 ± 1.97 years (range 6-14 years) and mean BMI z-score 1.85 ± 0.74 (range -0.97 ± 3.27). Peer victimization and self-concept were assessed with a revised Olweus Bully/Victim Questionnaire and with the Self-Perception Profile for Children. A structural equation model approach was used to determine the associations among variables, testing two competing models. In both models, path analysis revealed that BMI z-score was directly associated with peer victimization and self-concept in multiple domains. In the first model, peer victimization mediated the relationship between BMI-score and self-concept, whereas in the alternative model, self-concept mediated the relationship between BMI z-score and peer victimization. Interaction analyses revealed that social competence moderated the relationship between BMI z-score and peer victimization and that peer victimization moderated the relationship between BMI z-score and physical appearance. Higher levels of BMI z-score are a risk factor for peer victimization and poor self-concept. When high levels of BMI z-score are associated with a negative self-concept, the risk of victimization increases. Preventive and supportive interventions are needed to avoid negative consequences on quality of life in children and adolescents with obesity.

Validation and Genotyping of Multiple Human Polymorphic Inversions Mediated by Inverted Repeats Reveals a High Degree of Recurrence

PubMed Central

Aguado, Cristina; Gayà-Vidal, Magdalena; Villatoro, Sergi; Oliva, Meritxell; Izquierdo, David; Giner-Delgado, Carla; Montalvo, Víctor; García-González, Judit; Martínez-Fundichely, Alexander; Capilla, Laia; Ruiz-Herrera, Aurora; Estivill, Xavier; Puig, Marta; Cáceres, Mario

2014-01-01

In recent years different types of structural variants (SVs) have been discovered in the human genome and their functional impact has become increasingly clear. Inversions, however, are poorly characterized and more difficult to study, especially those mediated by inverted repeats or segmental duplications. Here, we describe the results of a simple and fast inverse PCR (iPCR) protocol for high-throughput genotyping of a wide variety of inversions using a small amount of DNA. In particular, we analyzed 22 inversions predicted in humans ranging from 5.1 kb to 226 kb and mediated by inverted repeat sequences of 1.6–24 kb. First, we validated 17 of the 22 inversions in a panel of nine HapMap individuals from different populations, and we genotyped them in 68 additional individuals of European origin, with correct genetic transmission in ∼12 mother-father-child trios. Global inversion minor allele frequency varied between 1% and 49% and inversion genotypes were consistent with Hardy-Weinberg equilibrium. By analyzing the nucleotide variation and the haplotypes in these regions, we found that only four inversions have linked tag-SNPs and that in many cases there are multiple shared SNPs between standard and inverted chromosomes, suggesting an unexpected high degree of inversion recurrence during human evolution. iPCR was also used to check 16 of these inversions in four chimpanzees and two gorillas, and 10 showed both orientations either within or between species, providing additional support for their multiple origin. Finally, we have identified several inversions that include genes in the inverted or breakpoint regions, and at least one disrupts a potential coding gene. Thus, these results represent a significant advance in our understanding of inversion polymorphism in human populations and challenge the common view of a single origin of inversions, with important implications for inversion analysis in SNP-based studies. PMID:24651690

Prospective relations between family conflict and adolescent maladjustment: security in the family system as a mediating process.

PubMed

Cummings, E Mark; Koss, Kalsea J; Davies, Patrick T

2015-04-01

Conflict in specific family systems (e.g., interparental, parent-child) has been implicated in the development of a host of adjustment problems in adolescence, but little is known about the impact of family conflict involving multiple family systems. Furthermore, questions remain about the effects of family conflict on symptoms of specific disorders and adjustment problems and the processes mediating these effects. The present study prospectively examines the impact of family conflict and emotional security about the family system on adolescent symptoms of specific disorders and adjustment problems, including the development of symptoms of anxiety, depression, conduct problems, and peer problems. Security in the family system was examined as a mediator of these relations. Participants included 295 mother-father-adolescent families (149 girls) participating across three annual time points (grades 7-9). Including auto-regressive controls for initial levels of emotional insecurity and multiple adjustment problems (T1), higher-order emotional insecurity about the family system (T2) mediated relations between T1 family conflict and T3 peer problems, anxiety, and depressive symptoms. Further analyses supported specific patterns of emotional security/insecurity (i.e., security, disengagement, preoccupation) as mediators between family conflict and specific domains of adolescent adjustment. Family conflict was thus found to prospectively predict the development of symptoms of multiple specific adjustment problems, including symptoms of depression, anxiety, conduct problems, and peer problems, by elevating in in adolescent's emotional insecurity about the family system. The clinical implications of these findings are considered.

Physical activity, self-efficacy, and health-related quality of life in persons with multiple sclerosis: analysis of associations between individual-level changes over one year.

PubMed

Motl, Robert W; McAuley, Edward; Wynn, Daniel; Sandroff, Brian; Suh, Yoojin

2013-03-01

Physical activity and self-efficacy represent behavioral and psychological factors, respectively, that are compromised in persons with multiple sclerosis (MS), but might be modifiable through intervention and result in better health-related quality of life (HRQOL). The present study adopted a panel research design and examined the associations between individual-level changes in physical activity, self-efficacy, and HRQOL over a one-year period in persons with MS. The sample consisted of 269 persons with relapsing-remitting MS who completed the Godin Leisure-Time Questionnaire (GLTEQ), Multiple Sclerosis Self-Efficacy (MSSE) Scale, and Multiple Sclerosis Quality of Life-29 (MSIS-29) Scale on two occasions that were separated by 1 year. The data were analyzed using panel analysis in Mplus 3.0. The initial panel analysis indicated that individual-level change in physical activity was associated with individual-level change in both physical and psychological HRQOL. The subsequent panel analysis indicated that (a) individual-level change in self-efficacy for functioning with MS was associated with individual-level change in physical HRQOL, whereas individual-level change in self-efficacy for control was associated with individual-level change in psychological HRQOL; (b) individual-level change in self-efficacy for functioning with MS, but not self-efficacy for control, mediated the association between individual-level change in physical activity and physical HRQOL; and (c) individual-level change in self-efficacy for controlling MS was the strongest predictor of individual-level change in HRQOL. Physical activity and self-efficacy both might be important targets of subsequent behavioral and self-management interventions for improving the HRQOL of persons with MS, although self-efficacy is seemingly more important than physical activity.

Evaluation of the In Vivo Therapeutic Effects of Radix Paeoniae Rubra Ethanol Extract with the Hypoglycemic Activities Measured from Multiple Cell-Based Assays

PubMed Central

Chang, Chia-Chuan; Yuan, Wei; Lin, Yun-Lian; Liu, Ren-Shyan; Juan, Yi-Chen; Sun, Wan-Hua; Tsay, Huey Jen; Lee, Yu-Ching

2016-01-01

Background. Radix Paeoniae Rubra (Chi Shao) contains several phytochemicals with hypoglycemic actions. Current research aims to explore potential insulinotropic effects and long-term therapeutic efficacy of such herb against type 2 diabetes. Methods. Composition analysis for the ethanol extract (PRExt) was executed by high performance liquid chromatography. Polyphenol-enriched fraction was characterized by high pressure size exclusion chromatography. Multiple cell platforms were employed to evaluate hypoglycemic bioactivities. In animal experiments, blood glucose, the homeostasis model assessment (HOMA)-index assessment, glucose tolerance test, and in vivo glucose uptake were all measured. Additional effects of PRExt on obesity and hepatic steatosis were evaluated by serum and histological analysis. Results. PRExt provides multiple hypoglycemic effects including the enhancement of glucose-mediated insulin secretion. Pentagalloylglucose and polyphenol-enriched fraction are two insulinotropic constituents. Moreover, PRExt intraperitoneal injection causes acute hypoglycemic effects on fasted db/db mice. Oral administration of PRExt (200 mg/kg b.w.) gradually reduces blood glucose in db/db mice to the level similar to that in C57J/B6 mice after 30 days. The improvement of glucose intolerance, HOMA-index, and in vivo glucose uptake is evident in addition to the weight loss effect and attenuation of hepatic steatosis. Conclusion. PRExt is an effective antidiabetic herbal extract with multiple hypoglycemic bioactivities. PMID:28018473

Linguistic analysis of verbal and non-verbal communication in the operating room.

PubMed

Moore, Alison; Butt, David; Ellis-Clarke, Jodie; Cartmill, John

2010-12-01

Surgery can be a triumph of co-operation, the procedure evolving as a result of joint action between multiple participants. The communication that mediates the joint action of surgery is conveyed by verbal but particularly by non-verbal signals. Competing priorities superimposed by surgical learning must also be negotiated within this context and this paper draws on techniques of systemic functional linguistics to observe and analyse the flow of information during such a phase of surgery. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of the Mediator transcription complex.

PubMed

Lewis, Brian A

2010-01-15

The regulation of transcription and of many other cellular processes involves large multi-subunit protein complexes. In the context of transcription, it is known that these complexes serve as regulatory platforms that connect activator DNA-binding proteins to a target promoter. However, there is still a lack of understanding regarding the function of these complexes. Why do multi-subunit complexes exist? What is the molecular basis of the function of their constituent subunits, and how are these subunits organized within a complex? What is the reason for physical connections between certain subunits and not others? In this article, I address these issues through a model of network allostery and its application to the eukaryotic RNA polymerase II Mediator transcription complex. The multiple allosteric networks model (MANM) suggests that protein complexes such as Mediator exist not only as physical but also as functional networks of interconnected proteins through which information is transferred from subunit to subunit by the propagation of an allosteric state known as conformational spread. Additionally, there are multiple distinct sub-networks within the Mediator complex that can be defined by their connections to different subunits; these sub-networks have discrete functions that are activated when specific subunits interact with other activator proteins.

Apoptosis induction in duck tissues during duck hepatitis A virus type 1 infection.

PubMed

Sheng, X D; Zhang, W P; Zhang, Q R; Gu, C Q; Hu, X Y; Cheng, G F

2014-03-01

To investigate the role of apoptosis in duck viral hepatitis pathogenesis, 4- and 21-d-old ducks were inoculated with duck hepatitis A virus serotype 1 and killed at 2, 6, 12, 24, and 48 h postinfection. TdT-mediated dUTP nick-end labeling was used to detect apoptosis cells. Expression profiles of apoptosis-related genes including caspase-3, -8, -9, and Bcl-2 in spleen, bursa of Fabricius, liver, and the quantity of virus in blood were examined using real-time PCR. The TdT-mediated dUTP nick-end labeling analysis indicated there was a significant difference of apoptotic cells between treatments and controls. The same difference also appeared in virus amount variation in blood during infection. Gene expression analysis revealed that the apoptosis-related gene expression profile was different in the 2 groups, and also different between various organs. This study suggested that apoptosis may play an important role in duck hepatitis A virus serotype 1 infection, and apoptosis suppression might facilitate virus multiplication, resulting in the highest virus concentration in the host.

Indirect detection constraints on s- and t-channel simplified models of dark matter

NASA Astrophysics Data System (ADS)

Carpenter, Linda M.; Colburn, Russell; Goodman, Jessica; Linden, Tim

2016-09-01

Recent Fermi-LAT observations of dwarf spheroidal galaxies in the Milky Way have placed strong limits on the gamma-ray flux from dark matter annihilation. In order to produce the strongest limit on the dark matter annihilation cross section, the observations of each dwarf galaxy have typically been "stacked" in a joint-likelihood analysis, utilizing optical observations to constrain the dark matter density profile in each dwarf. These limits have typically been computed only for singular annihilation final states, such as b b ¯ or τ+τ- . In this paper, we generalize this approach by producing an independent joint-likelihood analysis to set constraints on models where the dark matter particle annihilates to multiple final-state fermions. We interpret these results in the context of the most popular simplified models, including those with s- and t-channel dark matter annihilation through scalar and vector mediators. We present our results as constraints on the minimum dark matter mass and the mediator sector parameters. Additionally, we compare our simplified model results to those of effective field theory contact interactions in the high-mass limit.

A Tutorial in Bayesian Potential Outcomes Mediation Analysis.

PubMed

Miočević, Milica; Gonzalez, Oscar; Valente, Matthew J; MacKinnon, David P

2018-01-01

Statistical mediation analysis is used to investigate intermediate variables in the relation between independent and dependent variables. Causal interpretation of mediation analyses is challenging because randomization of subjects to levels of the independent variable does not rule out the possibility of unmeasured confounders of the mediator to outcome relation. Furthermore, commonly used frequentist methods for mediation analysis compute the probability of the data given the null hypothesis, which is not the probability of a hypothesis given the data as in Bayesian analysis. Under certain assumptions, applying the potential outcomes framework to mediation analysis allows for the computation of causal effects, and statistical mediation in the Bayesian framework gives indirect effects probabilistic interpretations. This tutorial combines causal inference and Bayesian methods for mediation analysis so the indirect and direct effects have both causal and probabilistic interpretations. Steps in Bayesian causal mediation analysis are shown in the application to an empirical example.

Sensitivity analysis for linear structural equation models, longitudinal mediation with latent growth models and blended learning in biostatistics education

NASA Astrophysics Data System (ADS)

Sullivan, Adam John

In chapter 1, we consider the biases that may arise when an unmeasured confounder is omitted from a structural equation model (SEM) and sensitivity analysis techniques to correct for such biases. We give an analysis of which effects in an SEM are and are not biased by an unmeasured confounder. It is shown that a single unmeasured confounder will bias not just one but numerous effects in an SEM. We present sensitivity analysis techniques to correct for biases in total, direct, and indirect effects when using SEM analyses, and illustrate these techniques with a study of aging and cognitive function. In chapter 2, we consider longitudinal mediation with latent growth curves. We define the direct and indirect effects using counterfactuals and consider the assumptions needed for identifiability of those effects. We develop models with a binary treatment/exposure followed by a model where treatment/exposure changes with time allowing for treatment/exposure-mediator interaction. We thus formalize mediation analysis with latent growth curve models using counterfactuals, makes clear the assumptions and extends these methods to allow for exposure mediator interactions. We present and illustrate the techniques with a study on Multiple Sclerosis(MS) and depression. In chapter 3, we report on a pilot study in blended learning that took place during the Fall 2013 and Summer 2014 semesters here at Harvard. We blended the traditional BIO 200: Principles of Biostatistics and created ID 200: Principles of Biostatistics and epidemiology. We used materials from the edX course PH207x: Health in Numbers: Quantitative Methods in Clinical & Public Health Research and used. These materials were used as a video textbook in which students would watch a given number of these videos prior to class. Using surveys as well as exam data we informally assess these blended classes from the student's perspective as well as a comparison of these students with students in another course, BIO 201: Introduction to Statistical Methods in Fall 2013 as well as students from BIO 200 in Fall semesters of 1992 and 1993. We then suggest improvements upon our original course designs and follow up with an informal look at how these implemented changes affected the second offering of the newly blended ID 200 in Summer 2014.

Task analysis of information technology-mediated medication management in outpatient care.

PubMed

van Stiphout, F; Zwart-van Rijkom, J E F; Maggio, L A; Aarts, J E C M; Bates, D W; van Gelder, T; Jansen, P A F; Schraagen, J M C; Egberts, A C G; ter Braak, E W M T

2015-09-01

Educating physicians in the procedural as well as cognitive skills of information technology (IT)-mediated medication management could be one of the missing links for the improvement of patient safety. We aimed to compose a framework of tasks that need to be addressed to optimize medication management in outpatient care. Formal task analysis: decomposition of a complex task into a set of subtasks. First, we obtained a general description of the medication management process from exploratory interviews. Secondly, we interviewed experts in-depth to further define tasks and subtasks. Outpatient care in different fields of medicine in six teaching and academic medical centres in the Netherlands and the United States. 20 experts. Tasks were divided up into procedural, cognitive and macrocognitive tasks and categorized into the three components of dynamic decision making. The medication management process consists of three components: (i) reviewing the medication situation; (ii) composing a treatment plan; and (iii) accomplishing and communicating a treatment and surveillance plan. Subtasks include multiple cognitive tasks such as composing a list of current medications and evaluating the reliability of sources, and procedural tasks such as documenting current medication. The identified macrocognitive tasks were: planning, integration of IT in workflow, managing uncertainties and responsibilities, and problem detection. All identified procedural, cognitive and macrocognitive skills should be included when designing education for IT-mediated medication management. The resulting framework supports the design of educational interventions to improve IT-mediated medication management in outpatient care. © 2015 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Oxidation pattern of curdlan with TEMPO-mediated system.

PubMed

Tang, Rong; Hao, Jie; Zong, Ruijie; Wu, Fangxia; Zeng, Yangyang; Zhang, Zhenqing

2018-04-15

In this study, the TEMPO-mediated (TEMPO/NaBr/NaClO) oxidation pattern of curdlan was investigated through comprehensively structural analysis of the corresponding oxidized products. During the structural analysis, infrared spectroscopy (IR), nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography tandem multiple angle laser scattering (GPC-MALS) and ultra-high performance liquid chromatography tandem quadrupole time of flight mass spectrometry (UHPLC-Q/TOF-MS) were applied. As a result, the homogenous β1-3 polyglucuronic acids (MW, 49.8, 29.8 and 7.0 kDa) were obtained with proper amount of oxidant (5.36 mmol NaClO) at various temperatures (4, 25, 50 °C), respectively. Compared to the oxidation of 1-4 linked glucan (starch and cellulose) with TEMPO-mediated system at same reaction conditions, higher degree of specific oxidation and less degradation were observed in that of 1-3 linked curdlan. The glycosylation at position 3 could stabilize the sugar ring, which inactivates the non-specific oxidation related hydroxyl groups on the sugar ring. Thus, the TEMPO-mediated system has higher selectivity to oxidize the primary hydroxyl groups of 1-3 linked curdlan and form polyglucuronic acid than those observed in the oxidation of starch and cellulose. In addition, same as those observed in previous work about starch, higher the temperature was used in the oxidation with TEMPO system, higher the activity of oxidant (NaClO solution) was, more non-specific oxidation occurred, and more the degradation were observed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mechanisms of Thrombocytopenia During Septic Shock: A Multiplex Cluster Analysis of Endogenous Sepsis Mediators.

PubMed

Bedet, Alexandre; Razazi, Keyvan; Boissier, Florence; Surenaud, Mathieu; Hue, Sophie; Giraudier, Stéphane; Brun-Buisson, Christian; Mekontso Dessap, Armand

2018-06-01

Thrombocytopenia is a common feature of sepsis and may involve various mechanisms often related to the inflammatory response. This study aimed at evaluating factors associated with thrombocytopenia during human septic shock. In particular, we used a multiplex analysis to assess the role of endogenous sepsis mediators. Prospective, observational study. Thrombocytopenia was defined as an absolute platelet count <100 G/L or a 50% relative decrease in platelet count during the first week of septic shock. Plasma concentrations of 27 endogenous mediators involved in sepsis and platelet pathophysiology were assessed at day-1 using a multi-analyte Milliplex human cytokine kit. Patients with underlying diseases at risk of thrombocytopenia (hematological malignancies, chemotherapy, cirrhosis, and chronic heart failure) were excluded. Thrombocytopenia occurred in 33 (55%) of 60 patients assessed. Patients with thrombocytopenia were more prone to present with extrapulmonary infections and bacteremia. Disseminated intravascular coagulation was frequent (81%) in these patients. Unbiased hierarchical clustering identified five different clusters of sepsis mediators, including one with markers of platelet activation (e.g., thrombospondin-1) positively associated with platelet count, one with markers of inflammation (e.g., tumor necrosis factor alpha and heat shock protein 70), and endothelial dysfunction (e.g., intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) negatively associated with platelet count, and another involving growth factors of thrombopoiesis (e.g., thrombopoietin), also negatively associated with platelet count. Surrogates of hemodilution (e.g., hypoprotidemia and higher fluid balance) were also associated with thrombocytopenia. Multiple mechanisms seemed involved in thrombocytopenia during septic shock, including endothelial dysfunction/coagulopathy, hemodilution, and altered thrombopoiesis.

When it comes to lifestyle recommendations, more is sometimes less: a meta-analysis of theoretical assumptions underlying the effectiveness of interventions promoting multiple behavior domain change.

PubMed

Wilson, Kristina; Senay, Ibrahim; Durantini, Marta; Sánchez, Flor; Hennessy, Michael; Spring, Bonnie; Albarracín, Dolores

2015-03-01

A meta-analysis of 150 research reports summarizing the results of multiple behavior domain interventions examined theoretical predictions about the effects of the included number of recommendations on behavioral and clinical change in the domains of smoking, diet, and physical activity. The meta-analysis yielded 3 main conclusions. First, there is a curvilinear relation between the number of behavioral recommendations and improvements in behavioral and clinical measures, with a moderate number of recommendations producing the highest level of change. A moderate number of recommendations is likely to be associated with stronger effects because the intervention ensures the necessary level of motivation to implement the recommended changes, thereby increasing compliance with the goals set by the intervention, without making the intervention excessively demanding. Second, this curve was more pronounced when samples were likely to have low motivation to change, such as when interventions were delivered to nonpatient (vs. patient) populations, were implemented in nonclinic (vs. clinic) settings, used lay community (vs. expert) facilitators, and involved group (vs. individual) delivery formats. Finally, change in behavioral outcomes mediated the effects of number of recommended behaviors on clinical change. These findings provide important insights that can help guide the design of effective multiple behavior domain interventions. PsycINFO Database Record (c) 2015 APA, all rights reserved.

When It Comes to Lifestyle Recommendations, More is Sometimes Less: A Meta-Analysis of Theoretical Assumptions Underlying the Effectiveness of Interventions Promoting Multiple Behavior Domain Change

PubMed Central

Wilson, Kristina; Senay, Ibrahim; Durantini, Marta; Sánchez, Flor; Hennessy, Michael; Spring, Bonnie; Albarracín, Dolores

2016-01-01

A meta-analysis of 150 research reports summarizing the results of multiple behavior domain interventions examined theoretical predictions about the effects of the included number of recommendations on behavioral and clinical change in the domains of smoking, diet, and physical activity. The meta-analysis yielded three main conclusions. First, there is a curvilinear relation between the number of behavioral recommendations and improvements in behavioral and clinical measures, with a moderate number of recommendations producing the highest level of change. A moderate number of recommendations is likely to be associated with stronger effects because the intervention ensures the necessary level of motivation to implement the recommended changes, thereby increasing compliance with the goals set by the intervention, without making the intervention excessively demanding. Second, this curve was more pronounced when samples were likely to have low motivation to change, such as when interventions were delivered to non-patient (vs. patient) populations, were implemented in non-clinic (vs. clinic) settings, used lay community (vs. expert) facilitators, and involved group (vs. individual) delivery formats. Finally, change in behavioral outcomes mediated the effects of number of recommended behaviors on clinical change. These findings provide important insights that can help guide the design of effective multiple behavior domain interventions. PMID:25528345

Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells

PubMed Central

Kumari, Bharti; Jain, Pratistha; Das, Shaoli; Ghosal, Suman; Hazra, Bibhabasu; Trivedi, Ashish Chandra; Basu, Anirban; Chakrabarti, Jayprokas; Vrati, Sudhanshu; Banerjee, Arup

2016-01-01

Microglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation. PMID:26838068

Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells.

PubMed

Kumari, Bharti; Jain, Pratistha; Das, Shaoli; Ghosal, Suman; Hazra, Bibhabasu; Trivedi, Ashish Chandra; Basu, Anirban; Chakrabarti, Jayprokas; Vrati, Sudhanshu; Banerjee, Arup

2016-02-03

Microglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation.

Ants regulate colony spatial organization using multiple chemical road-signs

PubMed Central

Heyman, Yael; Shental, Noam; Brandis, Alexander; Hefetz, Abraham; Feinerman, Ofer

2017-01-01

Communication provides the basis for social life. In ant colonies, the prevalence of local, often chemically mediated, interactions introduces strong links between communication networks and the spatial distribution of ants. It is, however, unknown how ants identify and maintain nest chambers with distinct functions. Here, we combine individual tracking, chemical analysis and machine learning to decipher the chemical signatures present on multiple nest surfaces. We present evidence for several distinct chemical ‘road-signs' that guide the ants' movements within the dark nest. These chemical signatures can be used to classify nest chambers with different functional roles. Using behavioural manipulations, we demonstrate that at least three of these chemical signatures are functionally meaningful and allow ants from different task groups to identify their specific nest destinations, thus facilitating colony coordination and stabilization. The use of multiple chemicals that assist spatiotemporal guidance, segregation and pattern formation is abundant in multi-cellular organisms. Here, we provide a rare example for the use of these principles in the ant colony. PMID:28569746

One-step generation of complete gene knockout mice and monkeys by CRISPR/Cas9-mediated gene editing with multiple sgRNAs.

PubMed

Zuo, Erwei; Cai, Yi-Jun; Li, Kui; Wei, Yu; Wang, Bang-An; Sun, Yidi; Liu, Zhen; Liu, Jiwei; Hu, Xinde; Wei, Wei; Huo, Xiaona; Shi, Linyu; Tang, Cheng; Liang, Dan; Wang, Yan; Nie, Yan-Hong; Zhang, Chen-Chen; Yao, Xuan; Wang, Xing; Zhou, Changyang; Ying, Wenqin; Wang, Qifang; Chen, Ren-Chao; Shen, Qi; Xu, Guo-Liang; Li, Jinsong; Sun, Qiang; Xiong, Zhi-Qi; Yang, Hui

2017-07-01

The CRISPR/Cas9 system is an efficient gene-editing method, but the majority of gene-edited animals showed mosaicism, with editing occurring only in a portion of cells. Here we show that single gene or multiple genes can be completely knocked out in mouse and monkey embryos by zygotic injection of Cas9 mRNA and multiple adjacent single-guide RNAs (spaced 10-200 bp apart) that target only a single key exon of each gene. Phenotypic analysis of F0 mice following targeted deletion of eight genes on the Y chromosome individually demonstrated the robustness of this approach in generating knockout mice. Importantly, this approach delivers complete gene knockout at high efficiencies (100% on Arntl and 91% on Prrt2) in monkey embryos. Finally, we could generate a complete Prrt2 knockout monkey in a single step, demonstrating the usefulness of this approach in rapidly establishing gene-edited monkey models.

Ants regulate colony spatial organization using multiple chemical road-signs.

PubMed

Heyman, Yael; Shental, Noam; Brandis, Alexander; Hefetz, Abraham; Feinerman, Ofer

2017-06-01

Communication provides the basis for social life. In ant colonies, the prevalence of local, often chemically mediated, interactions introduces strong links between communication networks and the spatial distribution of ants. It is, however, unknown how ants identify and maintain nest chambers with distinct functions. Here, we combine individual tracking, chemical analysis and machine learning to decipher the chemical signatures present on multiple nest surfaces. We present evidence for several distinct chemical 'road-signs' that guide the ants' movements within the dark nest. These chemical signatures can be used to classify nest chambers with different functional roles. Using behavioural manipulations, we demonstrate that at least three of these chemical signatures are functionally meaningful and allow ants from different task groups to identify their specific nest destinations, thus facilitating colony coordination and stabilization. The use of multiple chemicals that assist spatiotemporal guidance, segregation and pattern formation is abundant in multi-cellular organisms. Here, we provide a rare example for the use of these principles in the ant colony.

Developmental Regulation of an Adhesin Gene during Cellular Morphogenesis in the Fungal Pathogen Candida albicans▿ †

PubMed Central

Argimón, Silvia; Wishart, Jill A.; Leng, Roger; Macaskill, Susan; Mavor, Abigail; Alexandris, Thomas; Nicholls, Susan; Knight, Andrew W.; Enjalbert, Brice; Walmsley, Richard; Odds, Frank C.; Gow, Neil A. R.; Brown, Alistair J. P.

2007-01-01

Candida albicans expresses specific virulence traits that promote disease establishment and progression. These traits include morphological transitions between yeast and hyphal growth forms that are thought to contribute to dissemination and invasion and cell surface adhesins that promote attachment to the host. Here, we describe the regulation of the adhesin gene ALS3, which is expressed specifically during hyphal development in C. albicans. Using a combination of reporter constructs and regulatory mutants, we show that this regulation is mediated by multiple factors at the transcriptional level. The analysis of ALS3 promoter deletions revealed that this promoter contains two activation regions: one is essential for activation during hyphal development, while the second increases the amplitude of this activation. Further deletion analyses using the Renilla reniformis luciferase reporter delineate the essential activation region between positions −471 and −321 of the promoter. Further 5′ or 3′ deletions block activation. ALS3 transcription is repressed mainly by Nrg1 and Tup1, but Rfg1 contributes to this repression. Efg1, Tec1, and Bcr1 are essential for the transcriptional activation of ALS3, with Tec1 mediating its effects indirectly through Bcr1 rather than through the putative Tec1 sites in the ALS3 promoter. ALS3 transcription is not affected by Cph2, but Cph1 contributes to full ALS3 activation. The data suggest that multiple morphogenetic signaling pathways operate through the promoter of this adhesin gene to mediate its developmental regulation in this major fungal pathogen. PMID:17277173

The effect of chronic seaweed subsidies on herbivory: plant-mediated fertilization pathway overshadows lizard-mediated predator pathways.

PubMed

Piovia-Scott, Jonah; Spiller, David A; Takimoto, Gaku; Yang, Louie H; Wright, Amber N; Schoener, Thomas W

2013-08-01

Flows of energy and materials link ecosystems worldwide and have important consequences for the structure of ecological communities. While these resource subsidies typically enter recipient food webs through multiple channels, most previous studies focussed on a single pathway of resource input. We used path analysis to evaluate multiple pathways connecting chronic marine resource inputs (in the form of seaweed deposits) and herbivory in a shoreline terrestrial ecosystem. We found statistical support for a fertilization effect (seaweed increased foliar nitrogen content, leading to greater herbivory) and a lizard numerical response effect (seaweed increased lizard densities, leading to reduced herbivory), but not for a lizard diet-shift effect (seaweed increased the proportion of marine-derived prey in lizard diets, but lizard diet was not strongly associated with herbivory). Greater seaweed abundance was associated with greater herbivory, and the fertilization effect was larger than the combined lizard effects. Thus, the bottom-up, plant-mediated effect of fertilization on herbivory overshadowed the top-down effects of lizard predators. These results, from unmanipulated shoreline plots with persistent differences in chronic seaweed deposition, differ from those of a previous experimental study of the short-term effects of a pulse of seaweed deposition: while the increase in herbivory in response to chronic seaweed deposition was due to the fertilization effect, the short-term increase in herbivory in response to a pulse of seaweed deposition was due to the lizard diet-shift effect. This contrast highlights the importance of the temporal pattern of resource inputs in determining the mechanism of community response to resource subsidies.

Racial Disparities in Cleanliness Attitudes Mediate Purchasing Attitudes Toward Cleaning Products: a Serial Mediation Model.

PubMed

Litman, Leib; Williams, Monnica T; Rosen, Zohn; Weinberger-Litman, Sarah L; Robinson, Jonathan

2017-09-22

The present study has three objectives (1) to examine whether there are differences in cleanliness concerns between African Americans and European Americans toward kitchen items that are known to be vectors of disease, (2) to examine whether disparities in cleanliness attitudes have an impact on purchasing attitudes toward kitchen cleaning products, and (3) to explore the mechanisms that may account for these differences utilizing a serial mediation model. Five hundred participants, 50% African American and 50% European American were shown a picture of a sponge cleaning product and filled out multiple survey instruments relating to cleanliness attitudes. We found greater concern with cleanliness of kitchen items (d = .46) and a greater willingness to purchase cleaning products among African Americans compared to European Americans (17 vs 10%). A serial mediation analysis revealed that general cleanliness concerns account for the increased willingness to spend money on cleaning products among African Americans. These results suggest that African Americans are more sensitive to issues of cleanliness compared to European Americans and, in particular, are more sensitive to cleanliness of kitchen items such as sponges, which can be vectors of food-borne pathogens. Potential reasons for the observed racial disparities in cleanliness attitudes and the implications of these results for public health are discussed.

Relationships among optimism, well-being, self-transcendence, coping, and social support in women during treatment for breast cancer.

PubMed

Matthews, Ellyn E; Cook, Paul F

2009-07-01

The impact of diagnosis and treatment for breast cancer, stressors that affect emotional well-being, is influenced by several psychosocial factors and the relationships among them. The purpose of this study was to investigate the relationship between optimism and emotional well-being (EWB) and the individual and combined mediation of this relationship by perceived social support (SS), problem focused coping (PFC), and self-transcendence in women with breast cancer during radiation therapy. Ninety-three women receiving radiation treatment for breast cancer completed questionnaires that measured EWB, optimism, SS, PFC, and self-transcendence. Correlational and multiple regression analysis revealed that optimism was positively related to EWB. Of the three mediators, self-transcendence alone was found to partially mediate the relationship between optimism and EWB. The relationship between optimism and PFC was not significant. Optimism was related to SS, but its indirect effect on EWB through SS did not reach significance. During breast cancer treatment, the positive effects of optimism on EWB are partially mediated by a woman's level of self-transcendence. Brief screening of women's optimism may help identify women at risk for psychological distress. Early detection and interventions to promote psychological adjustment throughout the cancer trajectory (e.g. enhancing self-transcendence) should receive attention in future research. (c) 2008 John Wiley & Sons, Ltd.

Socioeconomic position, health behaviors, and C-reactive protein: A moderated-mediation analysis

PubMed Central

Kershaw, Kiarri N.; Mezuk, Briana; Abdou, Cleopatra M.; Rafferty, Jane A.; Jackson, James S.

2010-01-01

Objective We sought to understand the link between low SEP and cardiovascular disease (CVD) by examining the association between SEP, health-related coping behaviors, and C-reactive protein (CRP), an inflammatory marker and independent risk factor for CVD in a US sample of adults. Design We used a multiple mediation model to evaluate how these behaviors work in concert to influence CRP levels and whether these relationships were moderated by gender and race/ethnicity. Main outcome measures CRP levels were divided into two categories: elevated CRP (3.1–10.0 mg/L) and normal CRP (≤ 3.0 mg/L). Results Both poverty and low educational attainment were associated with elevated CRP, and these associations were primarily explained through higher levels of smoking and lower levels of exercise. In the education model, poor diet also emerged as a significant mediator. These behaviors accounted for 87.9% of the total effect of education on CRP and 55.8% the total effect of poverty on CRP. We also found significant moderation of these mediated effects by gender and race/ethnicity. Conclusion These findings demonstrate the influence of socioeconomically-patterned environmental constraints on individual-level health behaviors. Specifically, reducing socioeconomic inequalities may have positive effects on CVD disparities through reducing cigarette smoking and increasing vigorous exercise. PMID:20496985

The association between negative affect and prescription opioid misuse in patients with chronic pain: The mediating role of opioid craving

PubMed Central

Martel, MO; Dolman, AJ; Edwards, RR; Jamison, RN; Wasan, AD

2013-01-01

Over the past decade, considerable research has accumulated showing that chronic pain patients experiencing high levels of negative affect (i.e., anxiety, depression) are at increased risk for prescription opioid misuse. The primary objective of the present study was to examine the factors that underlie the association between negative affect (NA) and prescription opioid misuse among patients with chronic pain. In this study, 82 patients with chronic musculoskeletal pain being prescribed opioid medication completed the Current Opioid Misuse Measure (COMM), a well-validated self-report questionnaire designed to assess prescription opioid misuse. Patients were also asked to complete self-report measures of pain intensity, NA, and opioid craving. A bootstrapped multiple mediation analysis was used to examine the mediating role of patients’ pain intensity and opioid craving in the association between NA and prescription opioid misuse. Consistent with previous research, we found a significant association between NA and prescription opioid misuse. Interestingly, results revealed that opioid craving, but not pain intensity, mediated the association between NA and opioid misuse. Discussion addresses the potential psychological and neurobiological factors that might contribute to the inter-relationships between NA, opioid craving, and prescription opioid misuse in patients with pain. The clinical implications of our findings are also discussed. PMID:24295876

Standardized Effect Size Measures for Mediation Analysis in Cluster-Randomized Trials

ERIC Educational Resources Information Center

Stapleton, Laura M.; Pituch, Keenan A.; Dion, Eric

2015-01-01

This article presents 3 standardized effect size measures to use when sharing results of an analysis of mediation of treatment effects for cluster-randomized trials. The authors discuss 3 examples of mediation analysis (upper-level mediation, cross-level mediation, and cross-level mediation with a contextual effect) with demonstration of the…

From the analysis of verbal data to the analysis of organizations: organizing as a dialogical process.

PubMed

Lorino, Philippe

2014-12-01

The analysis of conversational turn-taking and its implications on time (the speaker cannot completely anticipate the future effects of her/his speech) and sociality (the speech is co-produced by the various speakers rather than by the speaking individual) can provide a useful basis to analyze complex organizing processes and collective action: the actor cannot completely anticipate the future effects of her/his acts and the act is co-produced by multiple actors. This translation from verbal to broader classes of interaction stresses the performativity of speeches, the importance of the situation, the role of semiotic mediations to make temporally and spatially distant "ghosts" present in the dialog, and the dissymmetrical relationship between successive conversational turns, due to temporal irreversibility.

Social support as a mediator between problem behaviour and gambling: a cross-sectional study among 14-16-year-old Finnish adolescents.

PubMed

Räsänen, Tiina; Lintonen, Tomi; Tolvanen, Asko; Konu, Anne

2016-12-22

During the adolescent period, risk-taking behaviour increases. These behaviours can compromise the successful transition from adolescence to adulthood. The purpose of this study was to examine social support as a mediator of the relation between problem behaviour and gambling frequency among Finnish adolescents. Data were obtained from the national School Health Promotion Study (SHPS) from the years 2010 and 2011 (N=102 545). Adolescents were classified in the most homogeneous groups based on their problem behaviour via latent class analysis. Path analysis indicated that social support was negatively associated with problem behaviour, and problem behaviour and social support were negatively related (except for social support from friends among boys) to gambling. Social support from parents and school mediated, albeit weakly, the relations between problem behaviour and gambling among girls and boys. Problem behaviour may affect gambling through social support from school and parents. Thus prevention and intervention strategies should focus on strengthening adolescents' social support. In addition, because of the clustering of different problem behaviours instead of concentrating on a single form of problem behaviour multiple-behaviour interventions may have a much greater impact on public health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

False-Belief Understanding and Language Ability Mediate the Relationship between Emotion Comprehension and Prosocial Orientation in Preschoolers.

PubMed

Ornaghi, Veronica; Pepe, Alessandro; Grazzani, Ilaria

2016-01-01

Emotion comprehension (EC) is known to be a key correlate and predictor of prosociality from early childhood. In the present study, we examined this relationship within the broad theoretical construct of social understanding which includes a number of socio-emotional skills, as well as cognitive and linguistic abilities. Theory of mind, especially false-belief understanding, has been found to be positively correlated with both EC and prosocial orientation. Similarly, language ability is known to play a key role in children's socio-emotional development. The combined contribution of false-belief understanding and language to explaining the relationship between EC and prosociality has yet to be investigated. Thus, in the current study, we conducted an in-depth exploration of how preschoolers' false-belief understanding and language ability each contribute to modeling the relationship between children's comprehension of emotion and their disposition to act prosocially toward others, after controlling for age and gender. Participants were 101 4- to 6-year-old children (54% boys), who were administered measures of language ability, false-belief understanding, EC and prosocial orientation. Multiple mediation analysis of the data suggested that false-belief understanding and language ability jointly and fully mediated the effect of preschoolers' EC on their prosocial orientation. Analysis of covariates revealed that gender exerted no statistically significant effect, while age had a trivial positive effect. Theoretical and practical implications of the findings are discussed.

‎ Anxiety Sensitivity Dimensions and Generalized Anxiety‏ ‏Severity: The ‎Mediating Role of Experiential Avoidance and Repetitive‏ ‏Negative Thinking‎ ‎

PubMed Central

Mohammadkhani, Parvaneh; Pourshahbaz, Abbas; Kami, Maryam; Mazidi, Mahdi; Abasi, Imaneh‏

2016-01-01

Objective: Generalized anxiety disorder is one of the most common anxiety disorders in the general ‎population. Several studies suggest that anxiety sensitivity is a vulnerability factor in generalized ‎anxiety severity. However, some other studies suggest that negative repetitive thinking and ‎experiential avoidance as response factors can explain this relationship. Therefore, this study ‎aimed to investigate the mediating role of experiential avoidance and negative repetitive thinking ‎in the relationship between anxiety sensitivity and generalized anxiety severity.‎ Method: This was a cross-sectional and correlational study. A sample of 475 university students was ‎selected through stratified sampling method. The participants completed Anxiety Sensitivity ‎Inventory-3, Acceptance and Action Questionnaire-II, Perseverative Thinking Questionnaire, and ‎Generalized Anxiety Disorder 7-item Scale. Data were analyzed by Pearson correlation, multiple ‎regression analysis and path analysis.‎ Results: The results revealed a positive relationship between anxiety sensitivity, particularly cognitive ‎anxiety sensitivity, experiential avoidance, repetitive thinking and generalized anxiety severity. In ‎addition, findings showed that repetitive thinking, but not experiential avoidance, fully mediated ‎the relationship between cognitive anxiety sensitivity and generalized anxiety severity. α Level ‎was p<0.005.‎ Conclusion: Consistent with the trans-diagnostic hypothesis, anxiety sensitivity predicts generalized anxiety‏ ‏severity, but its effect is due to the generating repetitive negative thought.‎ PMID:27928245

Bridging the Divide: Cross-Cultural Mediation

ERIC Educational Resources Information Center

Mahan, Laura N.; Mahuna, Joshua M.

2017-01-01

The article strives to contribute to the growing field of conflict resolution by analyzing contrasting cross-cultural perceptions through insights from multiple areas to resolve intercultural conflicts and disputes. Western-centric mediation techniques are dissected in juxtaposition to indigenous methodologies in degrees of (1) substantiality and…

Evolved differences in larval social behavior mediated by novel pheromones

USDA-ARS?s Scientific Manuscript database

Pheromones, chemical signals that convey social information, mediate many insect social behaviors in both adult and immature stages. Multiple pheromones and neural pathways that underlie adult social behavior have been described in the genetic model organism, Drosophila melanogaster, but there is no...

Strategic Planning for Divorce Mediation.

ERIC Educational Resources Information Center

Weingarten, Helen R.

1986-01-01

Presents a theoretical model that focuses attention on the multiple arenas of life that are disrupted by divorce, the emotional stages of divorce, and the interpersonal dynamics of separating couples. Discusses the implications of these factors for strategically planning and carrying out the mediation process. (Author/ABB)

Mediation of psychosocial determinants in the relation between socio-economic status and adolescents' diet quality.

PubMed

Michels, Nathalie; Vynckier, Lisa; Moreno, Luis A; Beghin, Laurent; de la O, Alex; Forsner, Maria; Gonzalez-Gross, Marcela; Huybrechts, Inge; Iguacel, Isabel; Kafatos, Antonio; Kersting, Mathilde; Leclercq, Catherine; Manios, Yannis; Marcos, Ascension; Molnar, Denes; Sjöström, Michael; Widhalm, Kurt; De Henauw, Stefaan

2018-04-01

To examine the underlying reasons for the positive relation between socio-economic status (SES) and the diet quality of adolescents. In 2081 adolescents (12.5-17.5 years) of the European HELENA study, a continuous variable on diet quality via 2-day 24-h recalls was available. SES was reflected by parental education, parental occupation and family affluence. Mediation by several psychosocial determinants was tested: self-efficacy, availability at school and home, social support, barriers, benefits, awareness and some self-reported influencers (parents, school, taste, health, friends, food readily available, easy preparation, hunger, price and habits). Multiple mediation analyses were adjusted for age, sex and country. The availability of soft drinks and fruit at home, social support, parental influence, barriers, price influence, taste influence, health influence and food being readily available were significant mediators. The multiple mediation indirect effect accounted for 23-64% of the total effect. Both occupation and education and both maternal and paternal factors could be explained by the mediation. The unavailability of soft drinks was the strongest mediator (17-44% of the total effect). Up to 64% of the positive relation between SES and the diet quality in adolescence could be explained by several healthy eating determinants. Focusing on these factors in low-SES populations can minimize social inequalities in diet and health by improving the diet of these specific adolescents.

Mother-child relationship quality and effective discipline as mediators of the 6-year effects of the New Beginnings Program for children from divorced families.

PubMed

Zhou, Qing; Sandler, Irwin N; Millsap, Roger E; Wolchik, Sharlene A; Dawson-McClure, Spring R

2008-08-01

This study examines whether program effects on mother-child relationship quality and effective discipline mediated the 6-year longitudinal effects of the New Beginnings Program (NBP) to improve mental health and competence outcomes in 218 adolescents from divorced families in a randomized experimental trial. The NBP is a theory-based and parenting-focused preventive intervention to help children adjust to divorce, and it has previously shown significant main and/or Program x Baseline Risk interaction effects to reduce adolescents' mental health and social adaptation problems and to promote competence. Mediation analyses were conducted using single- and two-group (high and low baseline risk) structural equation modeling. A multiple-methods and multiple-informants approach was used to assess the putative mediators and adolescents' outcomes. Results indicated that program-induced improvement in maternal effective discipline at posttest mediated the intervention effect on adolescents' GPA at the 6-year follow-up. Moreover, program-induced improvement in mother-child relationship quality mediated the intervention effect on adolescents' mental health problems for those with high baseline risk for maladjustment. The discussion focuses on the implications of the mediation findings for advancing the developmental theories that informed the design of the NBP and the implications for implementation of the NBP in community settings. Copyright 2008 APA, all rights reserved.

Academic Self-Efficacy Partially Mediates the Relationship between Scottish Index of Multiple Deprivation and Composite Attainment Score.

PubMed

Perry, John L; Dempster, Martin; McKay, Michael T

2017-01-01

A developing literature continues to testify to the relationship between higher socio-economic status (SES) and better academic attainment. However, the literature is complex in terms of the variety of SES and attainment indicators used. Against the backdrop of a Scottish Government initiative to close the attainment gap between higher and lower SES children, the present study examined the relationship between individual-level Scottish Index of Multiple Deprivation (SIMD) and National Lower Tariff Score in school children in the West of Scotland. Results showed a practically significant relationship between SIMD and Tariff Score. This relationship was partially mediated by higher academic self-efficacy, so that higher belief in academic competency partially mediated the SIMD-Tariff Score relationship. Further, this partial mediation was robust to the influence of gender, sensation seeking, level of school attendance and past month frequency of Heavy Episodic Drinking. It is suggested that increasing attendance and perceived academic competence are viable ways (among others) of attempting to close the attainment gap.

Academic Self-Efficacy Partially Mediates the Relationship between Scottish Index of Multiple Deprivation and Composite Attainment Score

PubMed Central

Perry, John L.; Dempster, Martin; McKay, Michael T.

2017-01-01

A developing literature continues to testify to the relationship between higher socio-economic status (SES) and better academic attainment. However, the literature is complex in terms of the variety of SES and attainment indicators used. Against the backdrop of a Scottish Government initiative to close the attainment gap between higher and lower SES children, the present study examined the relationship between individual-level Scottish Index of Multiple Deprivation (SIMD) and National Lower Tariff Score in school children in the West of Scotland. Results showed a practically significant relationship between SIMD and Tariff Score. This relationship was partially mediated by higher academic self-efficacy, so that higher belief in academic competency partially mediated the SIMD-Tariff Score relationship. Further, this partial mediation was robust to the influence of gender, sensation seeking, level of school attendance and past month frequency of Heavy Episodic Drinking. It is suggested that increasing attendance and perceived academic competence are viable ways (among others) of attempting to close the attainment gap. PMID:29163281

Brief Integrative Multiple Behavior Intervention Effects and Mediators for Adolescents

PubMed Central

(Chad) Werch, Chudley E.; Bian, Hui; Carlson, Joan; Moore, Michele J.; DiClemente, Carlo C.; Huang, I-Chan; Ames, Steven C.; Thombs, Dennis; Weiler, Robert M.; Pokorny, Steven B.

2015-01-01

This study evaluated the efficacy of a brief integrative multiple behavior intervention and assessed risk factors as mediators of behavioral outcomes among older adolescents. A randomized controlled trial was conducted with participants randomly assigned to either a brief intervention or standard care control with 3-month follow-up. A total of 479 students attending two public high schools participated. Participants receiving the intervention showed a significant reduction in quantity x frequency of alcohol use, and increases in fruit and vegetable consumption and frequency of relaxation activities, compared to those receiving the control, p’s =.01. No effects were found on cigarette and marijuana use, exercise and sleep. Effect sizes were small with alcohol use cessation effects reaching medium size. Intervention effects were mediated by changes in peer influenceability for alcohol use, and self-efficacy and self-image for health promoting behaviors. Findings suggest that the brief intervention resulted in health risk and promoting behavior improvements for adolescents, with outcomes mediated by several risk factors. PMID:20661637

College drinking behaviors: mediational links between parenting styles, parental bonds, depression, and alcohol problems.

PubMed

Patock-Peckham, Julie A; Morgan-Lopez, Antonio A

2007-09-01

Mediational links between parenting styles (authoritative, authoritarian, permissive), parental bond (positive, negative), depression, alcohol use and abuse were tested. A 2-group, multiple-indicator, multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. In general, a poor parental bond with one's father was highly predictive of depression, a well-known predictor of alcohol abuse and related problems for both genders. In contrast, a positive parental bond with one's father significantly mediated the positive effects of authoritative fathering on depression, which then decreased alcohol use problems for both genders. For women, a negative parental bond with one's father significantly mediated the effect of having an authoritarian father on depression, which increased alcohol use problems. These findings suggest that parental influences on pathways to alcohol abuse through depression (primarily through fathers for both genders) are distinct from pathways stemming from poor impulse control (with influences primarily from the same-sex parents for both genders).

Corticosterone regulates multiple colour traits in Lacerta [Zootoca] vivipara males.

PubMed

San-Jose, L M; Fitze, P S

2013-12-01

Ornamental colours usually evolve as honest signals of quality, which is supported by the fact that they frequently depend on individual condition. It has generally been suggested that some, but not all types of ornamental colours are condition dependent, indicating that different evolutionary mechanisms underlie the evolution of multiple types of ornamental colours even when these are exhibited by the same species. Stress hormones, which negatively affect condition, have been shown to affect colour traits based on different pigments and structures, suggesting that they mediate condition dependence of multiple ornament types both among and within individuals. However, studies investigating effects of stress hormones on different ornament types within individuals are lacking, and thus, evidence for this hypothesis is scant. Here, we investigated whether corticosterone mediates condition dependence of multiple ornaments by manipulating corticosterone levels and body condition (via food availability) using a two-factorial design and by assessing their effect on multiple colour traits in male common lizards. Corticosterone negatively affected ventral melanin- and carotenoid-based coloration, whereas food availability did not affect coloration, despite its significant effect on body condition. The corticosterone effect on melanin- and carotenoid-based coloration demonstrates the condition dependence of both ornaments. Moreover, corticosterone affected ventral coloration and had no effect on the nonsexually selected dorsal coloration, showing specific effects of corticosterone on ornamental ventral colours. This suggests that corticosterone simultaneously mediates condition dependence of multiple colour traits and that it therefore accounts for covariation among them, which may influence their evolution via correlational selection. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

Morphogenetic and chemical stability of long-term maintained Agrobacterium-mediated transgenic Catharanthus roseus plants.

PubMed

Verma, Priyanka; Sharma, Abhishek; Khan, Shamshad Ahmad; Mathur, Ajay Kumar; Shanker, Karuna

2015-01-01

Transgenic Catharanthus roseus plants (transgenic Dhawal [DT] and transgenic Nirmal [NT]) obtained from the Agrobacterium tumefaciens and Agrobacterium rhizognenes-mediated transformations, respectively, have been maintained in vitro for 5 years. Plants were studied at regular intervals for various parameters such as plant height, leaf size, multiplication rate, alkaloid profile and presence of marker genes. DT plant gradually lost the GUS gene expression and it was not detected in the fifth year while NT plant demonstrated the presence of genes rolA, rolB and rolC even in the fifth year, indicating the more stable nature of Ri transgene. Vindoline content in the DT was two times more than in non-transformed control plants. Alkaloid and tryptophan profiles were almost constant during the 5 years. The cluster analysis revealed that the DT plant is more close to the control Nirmal plant followed by NT plant.

Proposal for a telehealth concept in the translational research model.

PubMed

Silva, Angélica Baptista; Morel, Carlos Médicis; Moraes, Ilara Hämmerli Sozzi de

2014-04-01

To review the conceptual relationship between telehealth and translational research. Bibliographical search on telehealth was conducted in the Scopus, Cochrane BVS, LILACS and MEDLINE databases to find experiences of telehealth in conjunction with discussion of translational research in health. The search retrieved eight studies based on analysis of models of the five stages of translational research and the multiple strands of public health policy in the context of telehealth in Brazil. The models were applied to telehealth activities concerning the Network of Human Milk Banks, in the Telemedicine University Network. The translational research cycle of human milk collected, stored and distributed presents several integrated telehealth initiatives, such as video conferencing, and software and portals for synthesizing knowledge, composing elements of an information ecosystem, mediated by information and communication technologies in the health system. Telehealth should be composed of a set of activities in a computer mediated network promoting the translation of knowledge between research and health services.

The association between home environmental variables and soft drink consumption among adolescents. Exploration of mediation by individual cognitions and habit strength.

PubMed

Tak, N I; Te Velde, S J; Oenema, A; Van der Horst, K; Timperio, A; Crawford, D; Brug, J

2011-04-01

Soft-drink consumption is one of the important target behaviours for the prevention of excessive weight gain among adolescents. To be able to modify these behaviours in obesity prevention interventions, further understanding of the underlying factors and mediational pathways is required. The present study aimed to explore associations between home environment variables and adolescent soft drink consumption and potential mediation of these associations by individual cognitions derived from the Theory of Planned Behaviour and habit strength. The ENDORSE study (N=1005) provided data on soft drink consumption and on home environment variables related to soft drink consumption (availability, accessibility, parental modelling, and parental rules), cognitive variables (intention, attitude, perceived behaviour control, and parental norm) and habit strength. Multiple mediation analyses were conducted using regression analyses according to the steps described by MacKinnon to assess the association between home environment variables and soft drink consumption and mediation of these associations by cognitive variables and habit strength. The bootstrapping method was used to calculate the confidence intervals. There were significant associations between the home environment variables and soft drink consumption. After inclusion of the mediators the strength of these associations was reduced. In the multiple mediator models, habit strength (39.4-62.6%) and intention (19.1-36.6%) were the strongest mediators. Intention and habit strength partly mediate the associations between home environment factors and soft drink consumption, suggesting that home environment variables influence soft drink consumption both indirectly and directly. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

PubMed

Kakar, Sanjeev; Einhorn, Thomas A; Vora, Siddharth; Miara, Lincoln J; Hon, Gregory; Wigner, Nathan A; Toben, Daniel; Jacobsen, Kimberly A; Al-Sebaei, Maisa O; Song, Michael; Trackman, Philip C; Morgan, Elise F; Gerstenfeld, Louis C; Barnes, George L

2007-12-01

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways.

Depressive mood mediates the influence of social support on health-related quality of life in elderly, multimorbid patients

PubMed Central

2014-01-01

Background It is not well established how psychosocial factors like social support and depression affect health-related quality of life in multimorbid and elderly patients. We investigated whether depressive mood mediates the influence of social support on health-related quality of life. Methods Cross-sectional data of 3,189 multimorbid patients from the baseline assessment of the German MultiCare cohort study were used. Mediation was tested using the approach described by Baron and Kenny based on multiple linear regression, and controlling for socioeconomic variables and burden of multimorbidity. Results Mediation analyses confirmed that depressive mood mediates the influence of social support on health-related quality of life (Sobel’s p < 0.001). Multiple linear regression showed that the influence of depressive mood (β = −0.341, p < 0.01) on health-related quality of life is greater than the influence of multimorbidity (β = −0.234, p < 0.01). Conclusion Social support influences health-related quality of life, but this association is strongly mediated by depressive mood. Depression should be taken into consideration in research on multimorbidity, and clinicians should be aware of its importance when caring for multimorbid patients. Trial registration ISRCTN89818205 PMID:24708815

Best (but oft-forgotten) practices: mediation analysis.

PubMed

Fairchild, Amanda J; McDaniel, Heather L

2017-06-01

This contribution in the "Best (but Oft-Forgotten) Practices" series considers mediation analysis. A mediator (sometimes referred to as an intermediate variable, surrogate endpoint, or intermediate endpoint) is a third variable that explains how or why ≥2 other variables relate in a putative causal pathway. The current article discusses mediation analysis with the ultimate intention of helping nutrition researchers to clarify the rationale for examining mediation, avoid common pitfalls when using the model, and conduct well-informed analyses that can contribute to improving causal inference in evaluations of underlying mechanisms of effects on nutrition-related behavioral and health outcomes. We give specific attention to underevaluated limitations inherent in common approaches to mediation. In addition, we discuss how to conduct a power analysis for mediation models and offer an applied example to demonstrate mediation analysis. Finally, we provide an example write-up of mediation analysis results as a model for applied researchers. © 2017 American Society for Nutrition.

Best (but oft-forgotten) practices: mediation analysis12

PubMed Central

McDaniel, Heather L

2017-01-01

This contribution in the “Best (but Oft-Forgotten) Practices” series considers mediation analysis. A mediator (sometimes referred to as an intermediate variable, surrogate endpoint, or intermediate endpoint) is a third variable that explains how or why ≥2 other variables relate in a putative causal pathway. The current article discusses mediation analysis with the ultimate intention of helping nutrition researchers to clarify the rationale for examining mediation, avoid common pitfalls when using the model, and conduct well-informed analyses that can contribute to improving causal inference in evaluations of underlying mechanisms of effects on nutrition-related behavioral and health outcomes. We give specific attention to underevaluated limitations inherent in common approaches to mediation. In addition, we discuss how to conduct a power analysis for mediation models and offer an applied example to demonstrate mediation analysis. Finally, we provide an example write-up of mediation analysis results as a model for applied researchers. PMID:28446497

The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways.

PubMed

Youns, Mаhmoud; Abdel Halim Hegazy, Wael

2017-01-01

Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes.

The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways

PubMed Central

Youns, Mаhmoud; Abdel Halim Hegazy, Wael

2017-01-01

Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes. PMID:28052097

Bayesian Mediation Analysis

ERIC Educational Resources Information Center

Yuan, Ying; MacKinnon, David P.

2009-01-01

In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

TRIP-Br2 promotes oncogenesis in nude mice and is frequently overexpressed in multiple human tumors

PubMed Central

Cheong, Jit Kong; Gunaratnam, Lakshman; Zang, Zhi Jiang; Yang, Christopher M; Sun, Xiaoming; Nasr, Susan L; Sim, Khe Guan; Peh, Bee Keow; Rashid, Suhaimi Bin Abdul; Bonventre, Joseph V; Salto-Tellez, Manuel; Hsu, Stephen I

2009-01-01

Background Members of the TRIP-Br/SERTAD family of mammalian transcriptional coregulators have recently been implicated in E2F-mediated cell cycle progression and tumorigenesis. We, herein, focus on the detailed functional characterization of the least understood member of the TRIP-Br/SERTAD protein family, TRIP-Br2 (SERTAD2). Methods Oncogenic potential of TRIP-Br2 was demonstrated by (1) inoculation of NIH3T3 fibroblasts, which were engineered to stably overexpress ectopic TRIP-Br2, into athymic nude mice for tumor induction and (2) comprehensive immunohistochemical high-throughput screening of TRIP-Br2 protein expression in multiple human tumor cell lines and human tumor tissue microarrays (TMAs). Clinicopathologic analysis was conducted to assess the potential of TRIP-Br2 as a novel prognostic marker of human cancer. RNA interference of TRIP-Br2 expression in HCT-116 colorectal carcinoma cells was performed to determine the potential of TRIP-Br2 as a novel chemotherapeutic drug target. Results Overexpression of TRIP-Br2 is sufficient to transform murine fibroblasts and promotes tumorigenesis in nude mice. The transformed phenotype is characterized by deregulation of the E2F/DP-transcriptional pathway through upregulation of the key E2F-responsive genes CYCLIN E, CYCLIN A2, CDC6 and DHFR. TRIP-Br2 is frequently overexpressed in both cancer cell lines and multiple human tumors. Clinicopathologic correlation indicates that overexpression of TRIP-Br2 in hepatocellular carcinoma is associated with a worse clinical outcome by Kaplan-Meier survival analysis. Small interfering RNA-mediated (siRNA) knockdown of TRIP-Br2 was sufficient to inhibit cell-autonomous growth of HCT-116 cells in vitro. Conclusion This study identifies TRIP-Br2 as a bona-fide protooncogene and supports the potential for TRIP-Br2 as a novel prognostic marker and a chemotherapeutic drug target in human cancer. PMID:19152710

Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs.

PubMed

Friedenberg, Steven G; Buhrman, Greg; Chdid, Lhoucine; Olby, Natasha J; Olivry, Thierry; Guillaumin, Julien; O'Toole, Theresa; Goggs, Robert; Kennedy, Lorna J; Rose, Robert B; Meurs, Kathryn M

2016-03-01

Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher's exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.

Mediators of Stress and Role Satisfaction in Multiple Role Women.

ERIC Educational Resources Information Center

Hammond, Laura A.

Women involved in multiple life roles comprise a large segment of society, yet little is known about how stressful and satisfying they find this lifestyle, or about what characteristics are related to feeling stressed or satisfied. The purpose of this study was to examine role and life satisfaction and stress in women involved in multiple life…

Immune complex-mediated autoimmunity in a patient With Smith-Magenis syndrome (del 17p11.2).

PubMed

Yang, Jianying; Chandrasekharappa, Settara C; Vilboux, Thierry; Smith, Ann C M; Peterson, Erik J

2014-08-01

Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena.

Group I but not group II NPV induces antiviral effects in mammalian cells.

PubMed

Liang, Changyong; Song, Jianhua; Hu, Zhihong; Chen, Xinwen

2006-10-01

Nucleopolyhedrovirus (NPV) is divided into Group I and Group II based on the phylogenetic analysis. It has been reported that Group I NPVs such as Autographa californica multiple NPV (AcMNPV) can transduce mammalian cells, while Group II NPVs such as Helicoverpa armigera single NPV (HaSNPV) cannot. Here we report that AcMNPV was capable of stimulating antiviral activity in human hepatoma cells (SMMC-7721) manifested by inhibition of Vesicular Stomatitis virus (VSV) replication. In contrast, the HaSNPV and the Spodoptera exigua multiple NPV (SeMNPV) of group II had no inhibitory effect on VSV. Recombinant AcMNPV was shown to induce interferons alpha/beta even in the absence of transgene expression in human SMMC-7721 cells, while it mediated transgene expression in BHK and L929 mammalian cells without an ensuing antiviral activity.

Cardiomyocyte-Specific Ablation of Med1 Subunit of the Mediator Complex Causes Lethal Dilated Cardiomyopathy in Mice.

PubMed

Jia, Yuzhi; Chang, Hsiang-Chun; Schipma, Matthew J; Liu, Jing; Shete, Varsha; Liu, Ning; Sato, Tatsuya; Thorp, Edward B; Barger, Philip M; Zhu, Yi-Jun; Viswakarma, Navin; Kanwar, Yashpal S; Ardehali, Hossein; Thimmapaya, Bayar; Reddy, Janardan K

2016-01-01

Mediator, an evolutionarily conserved multi-protein complex consisting of about 30 subunits, is a key component of the polymerase II mediated gene transcription. Germline deletion of the Mediator subunit 1 (Med1) of the Mediator in mice results in mid-gestational embryonic lethality with developmental impairment of multiple organs including heart. Here we show that cardiomyocyte-specific deletion of Med1 in mice (csMed1-/-) during late gestational and early postnatal development by intercrossing Med1fl/fl mice to α-MyHC-Cre transgenic mice results in lethality within 10 days after weaning due to dilated cardiomyopathy-related ventricular dilation and heart failure. The csMed1-/- mouse heart manifests mitochondrial damage, increased apoptosis and interstitial fibrosis. Global gene expression analysis revealed that loss of Med1 in heart down-regulates more than 200 genes including Acadm, Cacna1s, Atp2a2, Ryr2, Pde1c, Pln, PGC1α, and PGC1β that are critical for calcium signaling, cardiac muscle contraction, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and peroxisome proliferator-activated receptor regulated energy metabolism. Many genes essential for oxidative phosphorylation and proper mitochondrial function such as genes coding for the succinate dehydrogenase subunits of the mitochondrial complex II are also down-regulated in csMed1-/- heart contributing to myocardial injury. Data also showed up-regulation of about 180 genes including Tgfb2, Ace, Atf3, Ctgf, Angpt14, Col9a2, Wisp2, Nppa, Nppb, and Actn1 that are linked to cardiac muscle contraction, cardiac hypertrophy, cardiac fibrosis and myocardial injury. Furthermore, we demonstrate that cardiac specific deletion of Med1 in adult mice using tamoxifen-inducible Cre approach (TmcsMed1-/-), results in rapid development of cardiomyopathy and death within 4 weeks. We found that the key findings of the csMed1-/- studies described above are highly reproducible in TmcsMed1-/- mouse heart. Collectively, these observations suggest that Med1 plays a critical role in the maintenance of heart function impacting on multiple metabolic, compensatory and reparative pathways with a likely therapeutic potential in the management of heart failure.

Sexual minority status and violence among HIV infected and at-risk women.

PubMed

Pyra, Maria; Weber, Kathleen; Wilson, Tracey E; Cohen, Jennifer; Murchison, Lynn; Goparaju, Lakshmi; Cohen, Mardge H

2014-08-01

Sexual minority women with and at-risk for human immunodeficiency virus (HIV) may face increased risks of violence. To understand the relationship between sexual minority status and violence; and how high-risk sex and substance use mediate that relationship among women with and at-risk for HIV. Longitudinal study of 1,235 HIV infected and 508 uninfected women of the Women's Interagency HIV Study (WIHS) cohort, from New York City, NY, Chicago, IL, Washington D.C., and San Francisco, CA, 1994-2012. Primary exposures are sexual identity (heterosexual, bisexual, lesbian/gay) and sexual behavior (male, female, or male & female partners). Primary outcomes are sexual abuse, intimate partner violence (IPV) and physical violence; high-risk sex and substance use were examined as mediators. Bisexual women were at increased odds for sexual abuse [aOR 1.56 (1.00, 2.44)], IPV [aOR 1.50 (1.08, 2.09)], and physical violence [aOR 1.77 (1.33, 2.37)] compared to heterosexual women. In a separate analysis, women who reported sex with men and women (WSMW) had increased odds for sexual abuse [aOR 1.65 (0.99, 2.77], IPV [aOR 1.50 (1.09, 2.06)] and physical violence [aOR 2.24 (1.69, 2.98)] compared to women having sex only with men (WSM). Using indirect effects, multiple sex partners, cocaine and marijuana were significant mediators for most forms of abuse. Transactional sex was only a mediator for bisexual women. Women who reported sex only with women (WSW) had lower odds of sexual abuse [aOR 0.23 (0.06, 0.89)] and physical violence [aOR 0.42 (0.21, 0.85)] compared to WSM. Women who identify as bisexual or report both male and female sex partners are most vulnerable to violence; multiple recent sex partners, transactional sex and some types of substance use mediate this relationship. Acknowledging sexual identity and behavior, while addressing substance use and high-risk sex in clinical and psychosocial settings, may help reduce violence exposure among women with and at-risk for HIV.

Parent-Reported Behavioral and Psychiatric Problems Mediate the Relationship between Sleep-Disordered Breathing and Cognitive Deficits in School-Aged Children.

PubMed

Smith, Dale L; Gozal, David; Hunter, Scott J; Kheirandish-Gozal, Leila

2017-01-01

Numerous studies over the past several decades have illustrated that children who suffer from sleep-disordered breathing (SDB) are at greater risk for cognitive, behavioral, and psychiatric problems. Although behavioral problems have been proposed as a potential mediator between SDB and cognitive functioning, these relationships have not been critically examined. This analysis is based on a community-based cohort of 1,115 children who underwent overnight polysomnography, and cognitive and behavioral phenotyping. Structural model of the relationships between SDB, behavior, and cognition, and two recently developed mediation approaches based on propensity score weighting and resampling were used to assess the mediational role of parent-reported behavior and psychiatric problems in the relationship between SDB and cognitive functioning. Multiple models utilizing two different SDB definitions further explored direct effects of SDB on cognition as well as indirect effects through behavioral pathology. All models were adjusted for age, sex, race, BMI z -score, and asthma status. Indirect effects of SDB through behavior problems were significant in all mediation models, while direct effects of SDB on cognition were not. The findings were consistent across different mediation procedures and remained essentially unaltered when different criteria for SDB, behavior, and cognition were used. Potential effects of SDB on cognitive functioning appear to occur through behavioral problems that are detectable in this pediatric population. Thus, early attentional or behavioral pathology may be implicated in the cognitive functioning deficits associated with SDB, and may present an early morbidity-related susceptibility biomarker.

Working Alliance and Stages of Change for Employment: The Intermediary Role of Autonomous Motivation, Outcome Expectancy and Vocational Rehabilitation Engagement.

PubMed

Iwanaga, Kanako; Chan, Fong; Tansey, Timothy N; Strauser, David; Ritter, Ellen; Bishop, Malachy; Brooks, Jessica

2018-05-30

Purpose Working alliance is one of the most important common factors for successful counseling/psychotherapy outcomes. Based on the empirical literature about working alliance, it seems that self-determination and self-efficacy theory (SDT/SET) can potentially be used as a motivational model to explain the relationship between working alliance and vocational rehabilitation (VR) outcomes. The purpose of this study is to evaluate three primary SDT/SET constructs, autonomous motivation, expectancy and engagement, as mediators for the relationship between working alliance and stages of change (SOC) for employment. Methods A serial multiple mediation analysis (SMMA) was computed to evaluate autonomy, outcome expectancy, and VR engagement as mediators of the relationship between working alliance and SOC for employment in a sample of 277 people with chronic illness and disability (CID) receiving services from state VR agencies in the United States. Results The SMMA results indicated that working alliance was positively associated with SOC for employment (total effect), while the direct effect between working alliance and SOC for employment was not significant after controlling for the effects of the mediators, indicating significant mediation effects. The mediation effects were estimates of the indirect effects for working alliance on SOC for employment through (a) autonomous motivation, (b) outcome expectancy, (c) VR engagement, and (d) autonomous motivation, outcome expectancy and VR engagement together. Conclusions The results indicated that a strong working alliance has the benefit of helping consumers develop autonomous motivation to work and increasing their vocational outcome expectancy and engagement in VR services, leading to employment.

What mediates the relationship between family meals and adolescent health issues.

PubMed

Franko, Debra L; Thompson, Douglas; Affenito, Sandra G; Barton, Bruce A; Striegel-Moore, Ruth H

2008-03-01

To determine whether the frequency of family meals in childhood is associated with positive health outcomes in adolescence through the mediating links of increased family cohesion and positive coping skills. Data were obtained from the National Heart, Lung, and Blood Institute Growth and Health Study (NGHS), a 10-year longitudinal study of 2,379 black and white girls assessed annually from ages 9-19. The mediational analysis framework of H. C. Kraemer and colleagues (2001) was used to test the hypothesis that the frequency of family meals in childhood (Study Years 1 and 3) would be related to health outcomes (Study Year 10) through the mediating links of family cohesion and coping skills (Study Years 7/8), after adjusting for baseline (Year 1) demographics as well as previous levels of the outcome variables (Years 5/6). Several measures of adolescent health variables were included as outcome measures. These included the Perceived Stress Scale, three Eating Disorders Inventory subscales (drive for thinness, body dissatisfaction, and bulimia), number of days of alcohol and tobacco consumption, and engaging in extreme weight control behaviors (e.g., self-induced vomiting). More frequent family meals in the first 3 study years predicted greater family cohesion and problem- and emotion-focused coping in Years 7 and 8. Family cohesion mediated family meals and risk of smoking in Year 10. Problem-focused coping mediated family meals and both stress and disordered eating-related attitudes and behaviors in Year 10. Eating together as a family during childhood may have multiple benefits in later years. (c) 2008 APA, all rights reserved

Multiple effects of the special AT-rich binding protein 1 (SATB1) in colon carcinoma.

PubMed

Frömberg, Anja; Rabe, Michael; Aigner, Achim

2014-12-01

SATB1 (special AT-rich binding protein 1) is a global chromatin organizer regulating the expression of a large number of genes. Overexpression has been found in various solid tumors and positively correlated with prognostic and clinicopathological properties. In colorectal cancer (CRC), SATB1 overexpression and its correlation with poor differentiation, invasive depth, TNM (tumor, nodes, metastases) stage and prognosis have been demonstrated. However, more detailed studies on the SATB1 functions in CRC are warranted. In this article, we comprehensively analyze the cellular and molecular role of SATB1 in CRC cell lines with different SATB1 expression levels by using RNAi-mediated knockdown. Using siRNAs with different knockdown efficacies, we demonstrate antiproliferative, cell cycle-inhibitory and proapoptotic effects of SATB1 knockdown in a SATB1 gene dose-dependent manner. Tumor growth inhibition is confirmed in vivo in a subcutaneous tumor xenograft mouse model using stable knockdown cells. The in-depth analysis of cellular effects reveals increased activities of caspases-3, -7, -8, -9 and other mediators of apoptotic pathways. Similarly, the analysis of E- and N-cadherin, slug, twist, β-catenin and MMP7 indicates SATB1 effects on epithelial-mesenchymal transition (EMT) and matrix breakdown. Our results also establish SATB1 effects on receptor tyrosine kinases and (proto-)oncogenes such as HER receptors and Pim-1. Taken together, this suggests a more complex molecular interplay between tumor-promoting and possible inhibitory effects in CRC by affecting multiple pathways and molecules involved in proliferation, cell cycle, EMT, invasion and cell survival. © 2014 UICC.

Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells

PubMed Central

Nishikawa, Yukihiro; Okuzaki, Daisuke; Fukushima, Kohshiro; Mukai, Satomi; Ohno, Shouichi; Ozaki, Yuki; Yabuta, Norikazu; Nojima, Hiroshi

2015-01-01

Withaferin A (WA), a major bioactive component of the Indian herb Withania somnifera, induces cell death (apoptosis/necrosis) in multiple types of tumor cells, but the molecular mechanism underlying this cytotoxicity remains elusive. We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD). WA also killed PC-3 cells in spheroid-forming medium. DNA microarray analysis revealed that WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs) in PC-3 and DU-145, but not in LNCaP and TIG-1. Western analysis revealed increased expression of c-Fos and reduced expression of the anti-apoptotic protein c-FLIP(L). Expression of HSPs such as HSPA6 and Hsp70 was conspicuously elevated; however, because siRNA-mediated depletion of HSF-1, an HSP-inducing transcription factor, reduced PC-3 cell viability, it is likely that these heat-shock genes were involved in protecting against cell death. Moreover, WA induced generation of reactive oxygen species (ROS) in PC-3 and DU-145, but not in normal fibroblasts. Immunocytochemistry and immuno-electron microscopy revealed that WA disrupted the vimentin cytoskeleton, possibly inducing the ROS generation, c-Fos expression and c-FLIP(L) suppression. These observations suggest that multiple events followed by disruption of the vimentin cytoskeleton play pivotal roles in WA-mediated cell death. PMID:26230090

Principal component analysis-based unsupervised feature extraction applied to in silico drug discovery for posttraumatic stress disorder-mediated heart disease.

PubMed

Taguchi, Y-h; Iwadate, Mitsuo; Umeyama, Hideaki

2015-04-30

Feature extraction (FE) is difficult, particularly if there are more features than samples, as small sample numbers often result in biased outcomes or overfitting. Furthermore, multiple sample classes often complicate FE because evaluating performance, which is usual in supervised FE, is generally harder than the two-class problem. Developing sample classification independent unsupervised methods would solve many of these problems. Two principal component analysis (PCA)-based FE, specifically, variational Bayes PCA (VBPCA) was extended to perform unsupervised FE, and together with conventional PCA (CPCA)-based unsupervised FE, were tested as sample classification independent unsupervised FE methods. VBPCA- and CPCA-based unsupervised FE both performed well when applied to simulated data, and a posttraumatic stress disorder (PTSD)-mediated heart disease data set that had multiple categorical class observations in mRNA/microRNA expression of stressed mouse heart. A critical set of PTSD miRNAs/mRNAs were identified that show aberrant expression between treatment and control samples, and significant, negative correlation with one another. Moreover, greater stability and biological feasibility than conventional supervised FE was also demonstrated. Based on the results obtained, in silico drug discovery was performed as translational validation of the methods. Our two proposed unsupervised FE methods (CPCA- and VBPCA-based) worked well on simulated data, and outperformed two conventional supervised FE methods on a real data set. Thus, these two methods have suggested equivalence for FE on categorical multiclass data sets, with potential translational utility for in silico drug discovery.

Mental health and health-related quality of life of Chinese college students who were the victims of dating violence.

PubMed

Choi, Edmond P H; Wong, Janet Y H; Fong, Daniel Y T

2017-04-01

The aim of the study is to evaluate the mental health and health-related quality of life (HRQOL) of Chinese college students who were the victims of dating violence. Six hundred and fifty-two subjects were included in the data analysis. Subjects completed a structured questionnaire containing the Woman Abuse Screening tool, the Hospital Anxiety and Depression Scale, the 10-item version of the Perceived Stress Scale (PSS-10) and the World Health Organization Quality of Life-BREF Instrument (WHOQOL-BREF). Analysis by independent t test suggested that victims of dating violence had more severe depressive, anxiety and stress symptoms and poorer HRQOL than non-victims. Multiple linear regression models found that more severe dating violence victimization was associated with more severe depressive, anxiety and stress symptoms. The mediation analysis found that after simultaneously controlling for the degree of depressive, anxiety and stress symptoms, the direct effect between dating violence severity and HRQOL, as measured by overall HRQOL and the global health, physical and environment domains of the WHOQOL-BREF, was statistically insignificant, supporting a full-mediation model. The relationship between dating violence severity and the social domain of HRQOL was partially mediated by the degree of depressive, anxiety and stress symptoms. Victims of dating violence had poorer mental health and HRQOL than non-victims. The study findings affirm the importance of assessing depressive, anxiety and stress symptoms in victims and the need to improve their depressive, anxiety and stress symptoms to diminish the negative effects of dating violence, which are apparent in their HRQOL.

Explaining the effects of a 1-year intervention promoting a low fat diet in adolescent girls: a mediation analysis.

PubMed

Haerens, Leen; Cerin, Ester; Deforche, Benedicte; Maes, Lea; De Bourdeaudhuij, Ilse

2007-11-09

Although it is important to investigate how interventions work, no formal mediation analyses have been conducted to explain behavioral outcomes in school-based fat intake interventions in adolescents. The aim of the present study was to examine mediation effects of changes in psychosocial determinants of dietary fat intake (attitude, social support, self-efficacy, perceived benefits and barriers) on changes in fat intake in adolescent girls. Data from a 1-year prospective intervention study were used. A random sample of 804 adolescent girls was included in the study. Girls in the intervention group (n = 415) were exposed to a multi-component school-based intervention program, combining environmental changes with a computer tailored fat intake intervention and parental support. Fat intake and psychosocial determinants of fat intake were measured with validated self-administered questionnaires. To assess mediating effects, a product-of-coefficient test, appropriate for cluster randomized controlled trials, was used. None of the examined psychosocial factors showed a reliable mediating effect on changes in fat intake. The single-mediator model revealed a statistically significant suppression effect of perceived barriers on changes in fat intake (p = 0.011). In the multiple-mediator model, this effect was no longer significant, which was most likely due to changes in perceived barriers being moderately related to changes in self-efficacy (-0.30) and attitude (-0.25). The overall mediated-suppressed effect of the examined psychosocial factors was virtually zero (total mediated effect = 0.001; SE = 7.22; p = 0.992). Given the lack of intervention effects on attitudes, social support, self-efficacy and perceived benefits and barriers, it is suggested that future interventions should focus on the identification of effective strategies for changing these theoretical mediators in the desired direction. Alternatively, it could be argued that these constructs need not be targeted in interventions aimed at adolescents, as they may not be responsible for the intervention effects on fat intake. To draw any conclusions regarding mediators of fat-intake change in adolescent' girls and regarding optimal future intervention strategies, more systematic research on the mediating properties of psychosocial variables is needed.

Bax Translocation Mediated Mitochondrial Apoptosis and Caspase Dependent Photosensitizing Effect of Ficus religiosa on Cancer Cells

PubMed Central

Thankayyan R, Santhosh Kumar; Sithul, Hima; Sreeharshan, Sreeja

2012-01-01

The main aim of the present work was to investigate the potential effect of acetone extract of Ficus religosa leaf (FAE) in multiple apoptosis signalling in human breast cancer cells. FAE treatment significantly induced dose and time dependent, irreversible inhibition of breast cancer cell growth with moderate toxicity to normal breast epithelial cells. This observation was validated using Sulforhodamine B assay. Cell cycle analysis by Flow cytometry showed cell cycle arrest in G1 phase and induction of sub-G0 peak. FAE induced chromatin condensation and displayed an increase in apoptotic population in Annexin V-FITC/PI (Fluorescein isothiocyanate/Propidium iodide) double staining. FAE stimulated the loss of mitochondrial membrane potential in multiple breast cancer cell lines when compared to normal diploid cells. To understand the role of Bax in FAE induced apoptosis, we employed a sensitive cell based platform of MCF-7 cells expressing Bax-EGFP. Bax translocation to mitochondria was accompanied by the disruption of mitochondrial membrane potential and marked elevation in LEHDase activity (Caspase 9). Consistent with this data, FAE induced Caspase activation as evidenced by ratio change in FRET Caspase sensor expressing MCF-7 cell line and cleavage of prominent Caspases and PARP. Interestingly, FAE accelerated cell death in a mitochondrial dependent manner in continuous live cell imaging mode indicating its possible photosensitizing effect. Intracellular generation of reactive oxygen species (ROS) by FAE played a critical role in mediating apoptotic cell death and photosensitizing activity. FAE induced dose and time dependent inhibition of cancer cell growth which was associated with Bax translocation and mitochondria mediated apoptosis with the activation of Caspase 9 dependent Caspase cascade. FAE also possessed strong photosensitizing effect on cancer cell line that was mediated through rapid mitochondrial transmembrane potential loss and partial Caspase activation involving generation of intracellular ROS. PMID:22792212

Overexpression of MIC-3 indicates a direct role for the MIC gene family in mediating Upland cotton (Gossypium hirsutum) resistance to root-knot nematode (Meloidogyne incognita).

PubMed

Wubben, Martin J; Callahan, Franklin E; Velten, Jeff; Burke, John J; Jenkins, Johnie N

2015-02-01

Transgene-based analysis of the MIC-3 gene provides the first report of a cotton gene having a direct role in mediating cotton resistance to root-knot nematode. Major quantitative trait loci have been mapped to Upland cotton (Gossypium hirsutum L.) chromosomes 11 and 14 that govern the highly resistant phenotype in response to infection by root-knot nematode (RKN; Meloidogyne incognita); however, nearly nothing is known regarding the underlying molecular determinants of this RKN-resistant phenotype. Multiple lines of circumstantial evidence have strongly suggested that the MIC (Meloidogyne Induced Cotton) gene family plays an integral role in mediating cotton resistance to RKN. In this report, we demonstrate that overexpression of MIC-3 in the RKN-susceptible genetic background Coker 312 reduces RKN egg production by ca. 60-75 % compared to non-transgenic controls and transgene-null sibling lines. MIC-3 transcript and protein overexpression were confirmed in root tissues of multiple independent transgenic lines with each line showing a similar level of increased resistance to RKN. In contrast to RKN fecundity, transgenic lines showed RKN-induced root galling similar to the susceptible controls. In addition, we determined that this effect of MIC-3 overexpression was specific to RKN as no effect was observed on reniform nematode (Rotylenchulus reniformis) reproduction. Transgenic lines did not show obvious alterations in growth, morphology, flowering, or fiber quality traits. Gene expression analyses showed that MIC-3 transcript levels in uninfected transgenic roots exceeded levels observed in RKN-infected roots of naturally resistant plants and that overexpression did not alter the regulation of native MIC genes in the genome. These results are the first report describing a direct role for a specific gene family in mediating cotton resistance to a plant-parasitic nematode.

Malleable machines in transcription regulation: the mediator complex.

PubMed

Tóth-Petróczy, Agnes; Oldfield, Christopher J; Simon, István; Takagi, Yuichiro; Dunker, A Keith; Uversky, Vladimir N; Fuxreiter, Monika

2008-12-01

The Mediator complex provides an interface between gene-specific regulatory proteins and the general transcription machinery including RNA polymerase II (RNAP II). The complex has a modular architecture (Head, Middle, and Tail) and cryoelectron microscopy analysis suggested that it undergoes dramatic conformational changes upon interactions with activators and RNAP II. These rearrangements have been proposed to play a role in the assembly of the preinitiation complex and also to contribute to the regulatory mechanism of Mediator. In analogy to many regulatory and transcriptional proteins, we reasoned that Mediator might also utilize intrinsically disordered regions (IDRs) to facilitate structural transitions and transmit transcriptional signals. Indeed, a high prevalence of IDRs was found in various subunits of Mediator from both Saccharomyces cerevisiae and Homo sapiens, especially in the Tail and the Middle modules. The level of disorder increases from yeast to man, although in both organisms it significantly exceeds that of multiprotein complexes of a similar size. IDRs can contribute to Mediator's function in three different ways: they can individually serve as target sites for multiple partners having distinctive structures; they can act as malleable linkers connecting globular domains that impart modular functionality on the complex; and they can also facilitate assembly and disassembly of complexes in response to regulatory signals. Short segments of IDRs, termed molecular recognition features (MoRFs) distinguished by a high protein-protein interaction propensity, were identified in 16 and 19 subunits of the yeast and human Mediator, respectively. In Saccharomyces cerevisiae, the functional roles of 11 MoRFs have been experimentally verified, and those in the Med8/Med18/Med20 and Med7/Med21 complexes were structurally confirmed. Although the Saccharomyces cerevisiae and Homo sapiens Mediator sequences are only weakly conserved, the arrangements of the disordered regions and their embedded interaction sites are quite similar in the two organisms. All of these data suggest an integral role for intrinsic disorder in Mediator's function.

A State Space Modeling Approach to Mediation Analysis

ERIC Educational Resources Information Center

Gu, Fei; Preacher, Kristopher J.; Ferrer, Emilio

2014-01-01

Mediation is a causal process that evolves over time. Thus, a study of mediation requires data collected throughout the process. However, most applications of mediation analysis use cross-sectional rather than longitudinal data. Another implicit assumption commonly made in longitudinal designs for mediation analysis is that the same mediation…

Social anxiety and heavy situational drinking: coping and conformity motives as multiple mediators.

PubMed

Terlecki, Meredith A; Buckner, Julia D

2015-01-01

Individuals with clinically elevated social anxiety are at greater risk for alcohol use disorder, and the relation between social anxiety and drinking problems is at least partially accounted for by drinking more in negative emotional (e.g., feeling sad or angry) and personal/intimate (e.g., before sexual intercourse) situations. Identification of cognitive/motivational factors related to drinking in these high-risk situations could inform the development of treatment and prevention interventions for these high-risk drinkers. The current cross-sectional study examined the mediating effect of drinking motives on the relationship between social anxiety and drinking these high-risk situations among undergraduates (N=232). Clinically elevated social anxiety was associated with greater coping and conformity motives. Both coping and conformity motives mediated the relation between social anxiety and heavier alcohol consumption in negative emotional and personal/intimate contexts. Multiple mediation analyses indicated that these motives work additively to mediate the social anxiety-drinking situations relationship, such that heavy situational drinking among undergraduates with clinically elevated social anxiety can be jointly attributed to desire to cope with negative affect and to avoid social scrutiny. Copyright © 2014 Elsevier Ltd. All rights reserved.

Are effort-reward imbalance and social isolation mediating the association between education and depressiveness? Baseline findings from the lidA(§)-study.

PubMed

du Prel, Jean-Baptist; Iskenius, Mario; Peter, Richard

2014-12-01

To investigate multiple mediations of the association between education and depressive symptoms (BDI-V) by work-related stress (ERI) and social isolation, the regional variation of the first mediation and a potential moderating effect of regional unemployment rate. 6339 employees born in 1959 and 1965 were randomly recruited from 222 sample points in a German cohort study on work, age, health and work participation. A multilevel model of moderated lower-level mediation was used to investigate the confirmatory research question. Multiple mediations were tested corresponding to Baron and Kenny. These analyses were stratified for age and adjusted for sex, negative affectivity and overcommitment. In the association between education and depressive symptoms, indirect effects of work-related stress and social isolation were significant in both age cohorts whereas a direct association was observable in the younger cohort, only. The significant regional variation in the association between work-related stress and depressive symptoms was not statistically explained by regional unemployment rate. Our findings point out that work-related stress and social isolation play an intermediary role between education and depressive symptoms in middle-aged employees.

Simple method for assembly of CRISPR synergistic activation mediator gRNA expression array.

PubMed

Vad-Nielsen, Johan; Nielsen, Anders Lade; Luo, Yonglun

2018-05-20

When studying complex interconnected regulatory networks, effective methods for simultaneously manipulating multiple genes expression are paramount. Previously, we have developed a simple method for generation of an all-in-one CRISPR gRNA expression array. We here present a Golden Gate Assembly-based system of synergistic activation mediator (SAM) compatible CRISPR/dCas9 gRNA expression array for the simultaneous activation of multiple genes. Using this system, we demonstrated the simultaneous activation of the transcription factors, TWIST, SNAIL, SLUG, and ZEB1 a human breast cancer cell line. Copyright © 2018 Elsevier B.V. All rights reserved.

Prospective Relations between Family Conflict and Adolescent Maladjustment: Security in the Family System as a Mediating Process

PubMed Central

Cummings, E. Mark; Koss, Kalsea J.; Davies, Patrick T.

2018-01-01

Conflict in specific family systems (e.g., interparental, parent-child) has been implicated in the development of a host of adjustment problems in adolescence, but little is known about the impact of family conflict involving multiple family systems. Furthermore, questions remain about the effects of family conflict on symptoms of specific disorders and adjustment problems and the processes mediating these effects. The present study prospectively examines the impact of family conflict and emotional security about the family system on adolescent symptoms of specific disorders and adjustment problems, including the development of symptoms of anxiety, depression, conduct problems, and peer problems. Security in the family system was examined as a mediator of these relations. Participants included 295 mother-father-adolescent families (149 girls) participating across three annual time points (grades 7–9). Including auto-regressive controls for initial levels of emotional insecurity and multiple adjustment problems (T1), higher-order emotional insecurity about the family system (T2) mediated relations between T1 family conflict and T3 peer problems, anxiety, and depressive symptoms. Further analyses supported specific patterns of emotional security/insecurity (i.e., security, disengagement, preoccupation) as mediators between family conflict and specific domains of adolescent adjustment. Family conflict was thus found to prospectively predict the development of symptoms of multiple specific adjustment problems, including symptoms of depression, anxiety, conduct problems, and peer problems, by elevating in in adolescent’s emotional insecurity about the family system. The clinical implications of these findings are considered. PMID:25131144

Investigating the effect of child maltreatment on early adolescent peer-on-peer sexual aggression: testing a multiple mediator model in a non-incarcerated sample of Danish adolescents.

PubMed

Bramsen, Rikke Holm; Lasgaard, Mathias; Koss, Mary P; Elklit, Ask; Banner, Jytte

2014-01-01

The aim of the present study was to investigate the relationship between child maltreatment and severe early adolescent peer-on-peer sexual aggression, using a multiple mediator model. The study comprised 330 male Grade 9 students with a mean age of 14.9 years (SD=0.5). Estimates from the mediation model indicated significant indirect effects of child physical abuse on sexual aggression via peer influence and insecure-hostile masculinity. No significant total effect of child sexual abuse and child neglect on sexual aggression was found. Findings of the present study identify risk factors that are potentially changeable and therefore of value in informing the design of prevention programs aiming at early adolescent peer-on-peer sexual aggression in at-risk youth.

An efficient in planta transformation of Jatropha curcas (L.) and multiplication of transformed plants through in vivo grafting.

PubMed

Jaganath, Balusamy; Subramanyam, Kondeti; Mayavan, Subramanian; Karthik, Sivabalan; Elayaraja, Dhandapani; Udayakumar, Rajangam; Manickavasagam, Markandan; Ganapathi, Andy

2014-05-01

An efficient and reproducible Agrobacterium-mediated in planta transformation was developed in Jatropha curcas. The various factors affecting J. curcas in planta transformation were optimized, including decapitation, Agrobacterium strain, pin-pricking, vacuum infiltration duration and vacuum pressure. Simple vegetative in vivo cleft grafting method was adopted in the multiplication of transformants without the aid of tissue culture. Among the various parameters evaluated, decapitated plants on pin-pricking and vacuum infiltrated at 250 mmHg for 3 min with the Agrobacterium strain EHA 105 harbouring the binary vector pGA 492 was proved to be efficient in all terms with a transformation efficiency of 62.66%. Transgene integration was evinced by the GUS histochemical analysis, and the GUS positive plants were subjected to grafting. Putatively transformed J. curcas served as "Scion" and the wild type J. curcas plant severed as "Stock". There was no occurrence of graft rejection and the plants were then confirmed by GUS histochemical analysis, polymerase chain reaction (PCR) and Southern hybridization. Genetic stability of the grafted plants was evaluated by using randomly amplified polymorphic DNA (RAPD), marker which showed 100% genetic stability between mother and grafted plants. Thus, an efficient in planta transformation and grafting based multiplication of J. curcas was established.

Trifactorial classification system for osteotome sinus floor elevation based on an observational retrospective analysis of 926 implants followed up to 10 years.

PubMed

French, David; Nadji, Nabil; Liu, Shawn X; Larjava, Hannu

2015-06-01

A novel osteotome trifactorial classification system is proposed for transcrestal osteotome-mediated sinus floor elevation (OSFE) sites that includes residual bone height (RBH), sinus floor anatomy (contour), and multiple versus single sites OSFE (tenting). An analysis of RBH, contour, and tenting was retrospectively applied to a cohort of 926 implants placed using OSFE without added bone graft and followed up to 10 years. RBH was divided into three groups: high (RBH > 6 mm), mid (RBH = 4.1 to 6 mm), and low (RBH = 2 to 4 mm). The sinus "contour" was divided into four groups: flat, concave, angle, and septa. For "tenting", single versus multiple adjacent OSFE sites were compared. The prevalence of flat sinus floors increased as RBH decreased. RBH was a significant predictor of failure with rates as follows: low- RBH = 5.1%, mid-RBH = 1.5%, and high-RBH = 0.4%. Flat sinus floors and single sites as compared to multiple sites had higher observed failure rates but neither achieved statistical significance; however, the power of the study was limited by low numbers of failures. The osteotome trifactorial classification system as proposed can assist planning OSFE cases and may allow better comparison of future OSFE studies.

Leadership and change commitment in the life insurance service context in Taiwan: the mediating-moderating role of job satisfaction.

PubMed

Yang, Yi-Feng

2011-06-01

The effects of transformational leadership and satisfaction were studied along with their interconnected effects (mediation and moderation) on commitment to change in the life insurance industry in two samples, sales managers and salespersons. A multiple mediated-moderated regression approach showed mediation and moderation to have statistically significant main effects on change commitment. Transformational leadership and satisfaction made a more important contribution to change commitment while job satisfaction had a mediating and moderating role that could enhance the relationships between leadership and change commitment. This information is of importance in building successful change commitment associations with customers.

Test of a Mediation Model of Perceived Organizational Support

ERIC Educational Resources Information Center

Chen, Zhen Xiong; Aryee, Samuel; Lee, Cynthia

2005-01-01

This study examined the mediating influence of trust in organization (TIO) and organization-based self-esteem (OBSE) on the relationship between perceived organization support (POS) and its work outcomes. Data were obtained from employee-supervisor dyads from multiple organizations located in a major city in southern China. Structural equation…

A Comparison of Three Tests of Mediation

ERIC Educational Resources Information Center

Warbasse, Rosalia E.

2009-01-01

A simulation study was conducted to evaluate the performance of three tests of mediation: the bias-corrected and accelerated bootstrap (Efron & Tibshirani, 1993), the asymmetric confidence limits test (MacKinnon, 2008), and a multiple regression approach described by Kenny, Kashy, and Bolger (1998). The evolution of these methods is reviewed and…

Mood instability as a precursor to depressive illness: A prospective and mediational analysis.

PubMed

Marwaha, Steven; Balbuena, Lloyd; Winsper, Catherine; Bowen, Rudy

2015-06-01

Mood instability levels are high in depression, but temporal precedence and potential mechanisms are unknown. Hypotheses tested were as follows: (1) mood instability is associated with depression cross-sectionally, (2) mood instability predicts new onset and maintenance of depression prospectively and (3) the mood instability and depression link are mediated by sleep problems, alcohol abuse and life events. Data from the National Psychiatric Morbidity Survey 2000 at baseline (N = 8580) and 18-month follow-up (N = 2413) were used. Regression modeling controlling for socio-demographic factors, anxiety and hypomanic mood was conducted. Multiple mediational analyses were used to test our conceptual path model. Mood instability was associated with depression cross-sectionally (odds ratio: 5.28; 95% confidence interval: [3.67, 7.59]; p < 0.001) and predicted depression inception (odds ratio: 2.43; 95% confidence interval: [1.03-5.76]; p = 0.042) after controlling for important confounders. Mood instability did not predict maintenance of depression. Sleep difficulties and severe problems with close friends and family significantly mediated the link between mood instability and new onset depression (23.05% and 6.19% of the link, respectively). Alcohol abuse and divorce were not important mediators in the model. Mood instability is a precursor of a depressive episode, predicting its onset. Difficulties in sleep are a significant part of the pathway. Interventions targeting mood instability and sleep problems have the potential to reduce the risk of depression. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Does food vendor density mediate the association between neighborhood deprivation and BMI?: a G-computation mediation analysis.

PubMed

Zhang, Y Tara; Laraia, Barbara A; Mujahid, Mahasin S; Tamayo, Aracely; Blanchard, Samuel D; Warton, E Margaret; Kelly, N Maggi; Moffet, Howard H; Schillinger, Dean; Adler, Nancy; Karter, Andrew J

2015-05-01

In previous research, neighborhood deprivation was positively associated with body mass index (BMI) among adults with diabetes. We assessed whether the association between neighborhood deprivation and BMI is attributable, in part, to geographic variation in the availability of healthful and unhealthful food vendors. Subjects were 16,634 participants of the Diabetes Study of Northern California, a multiethnic cohort of adults living with diabetes. Neighborhood deprivation and healthful (supermarket and produce) and unhealthful (fast food outlets and convenience stores) food vendor kernel density were calculated at each participant's residential block centroid. We estimated the total effect, controlled direct effect, natural direct effect, and natural indirect effect of neighborhood deprivation on BMI. Mediation effects were estimated using G-computation, a maximum likelihood substitution estimator of the G-formula that allows for complex data relations such as multiple mediators and sequential causal pathways. We estimated that if neighborhood deprivation was reduced from the most deprived to the least deprived quartile, average BMI would change by -0.73 units (95% confidence interval: -1.05, -0.32); however, we did not detect evidence of mediation by food vendor density. In contrast to previous findings, a simulated reduction in neighborhood deprivation from the most deprived to the least deprived quartile was associated with dramatic declines in both healthful and unhealthful food vendor density. Availability of food vendors, both healthful and unhealthful, did not appear to explain the association between neighborhood deprivation and BMI in this population of adults with diabetes.

Insecticide resistance is mediated by multiple mechanisms in recently introduced Aedes aegypti from Madeira Island (Portugal)

PubMed Central

Seixas, Gonçalo; Grigoraki, Linda; Weetman, David; Vicente, José Luís; Silva, Ana Clara; Pinto, João; Vontas, John

2017-01-01

Background Aedes aegypti is a major mosquito vector of arboviruses, including dengue, chikungunya and Zika. In 2005, Ae. aegypti was identified for the first time in Madeira Island. Despite an initial insecticide-based vector control program, the species expanded throughout the Southern coast of the island, suggesting the presence of insecticide resistance. Here, we characterized the insecticide resistance status and the underlying mechanisms of two populations of Ae. aegypti from Madeira Island, Funchal and Paúl do Mar. Methodology/Principal findings WHO susceptibility bioassays indicated resistance to cyfluthrin, permethrin, fenitrothion and bendiocarb. Use of synergists significantly increased mortality rates, and biochemical assays indicated elevated activities of detoxification enzymes, suggesting the importance of metabolic resistance. Microarray-based transcriptome analysis detected significant upregulation in both populations of nine cytochrome P450 oxidase genes (including four known pyrethroid metabolizing enzymes), the organophosphate metabolizer CCEae3a, Glutathione-S-transferases, and multiple putative cuticle proteins. Genotyping of knockdown resistance loci linked to pyrethroid resistance revealed fixation of the 1534C mutation, and presence with moderate frequencies of the V1016I mutation in each population. Conclusions/Significance Significant resistance to three major insecticide classes (pyrethroid, carbamate and organophosphate) is present in Ae. aegypti from Madeira Island, and appears to be mediated by multiple mechanisms. Implementation of appropriate resistance management strategies including rotation of insecticides with alternative modes of action, and methods other than chemical-based vector control are strongly advised to delay or reverse the spread of resistance and achieve efficient control. PMID:28742096

Overlapping Networks Engaged during Spoken Language Production and Its Cognitive Control

PubMed Central

Wise, Richard J.S.; Mehta, Amrish; Leech, Robert

2014-01-01

Spoken language production is a complex brain function that relies on large-scale networks. These include domain-specific networks that mediate language-specific processes, as well as domain-general networks mediating top-down and bottom-up attentional control. Language control is thought to involve a left-lateralized fronto-temporal-parietal (FTP) system. However, these regions do not always activate for language tasks and similar regions have been implicated in nonlinguistic cognitive processes. These inconsistent findings suggest that either the left FTP is involved in multidomain cognitive control or that there are multiple spatially overlapping FTP systems. We present evidence from an fMRI study using multivariate analysis to identify spatiotemporal networks involved in spoken language production in humans. We compared spoken language production (Speech) with multiple baselines, counting (Count), nonverbal decision (Decision), and “rest,” to pull apart the multiple partially overlapping networks that are involved in speech production. A left-lateralized FTP network was activated during Speech and deactivated during Count and nonverbal Decision trials, implicating it in cognitive control specific to sentential spoken language production. A mirror right-lateralized FTP network was activated in the Count and Decision trials, but not Speech. Importantly, a second overlapping left FTP network showed relative deactivation in Speech. These three networks, with distinct time courses, overlapped in the left parietal lobe. Contrary to the standard model of the left FTP as being dominant for speech, we revealed a more complex pattern within the left FTP, including at least two left FTP networks with competing functional roles, only one of which was activated in speech production. PMID:24966373

Overlapping networks engaged during spoken language production and its cognitive control.

PubMed

Geranmayeh, Fatemeh; Wise, Richard J S; Mehta, Amrish; Leech, Robert

2014-06-25

Spoken language production is a complex brain function that relies on large-scale networks. These include domain-specific networks that mediate language-specific processes, as well as domain-general networks mediating top-down and bottom-up attentional control. Language control is thought to involve a left-lateralized fronto-temporal-parietal (FTP) system. However, these regions do not always activate for language tasks and similar regions have been implicated in nonlinguistic cognitive processes. These inconsistent findings suggest that either the left FTP is involved in multidomain cognitive control or that there are multiple spatially overlapping FTP systems. We present evidence from an fMRI study using multivariate analysis to identify spatiotemporal networks involved in spoken language production in humans. We compared spoken language production (Speech) with multiple baselines, counting (Count), nonverbal decision (Decision), and "rest," to pull apart the multiple partially overlapping networks that are involved in speech production. A left-lateralized FTP network was activated during Speech and deactivated during Count and nonverbal Decision trials, implicating it in cognitive control specific to sentential spoken language production. A mirror right-lateralized FTP network was activated in the Count and Decision trials, but not Speech. Importantly, a second overlapping left FTP network showed relative deactivation in Speech. These three networks, with distinct time courses, overlapped in the left parietal lobe. Contrary to the standard model of the left FTP as being dominant for speech, we revealed a more complex pattern within the left FTP, including at least two left FTP networks with competing functional roles, only one of which was activated in speech production. Copyright © 2014 Geranmayeh et al.

Pseudomonas syringae pv. actinidiae Type III Effectors Localized at Multiple Cellular Compartments Activate or Suppress Innate Immune Responses in Nicotiana benthamiana.

PubMed

Choi, Sera; Jayaraman, Jay; Segonzac, Cécile; Park, Hye-Jee; Park, Hanbi; Han, Sang-Wook; Sohn, Kee Hoon

2017-01-01

Bacterial phytopathogen type III secreted (T3S) effectors have been strongly implicated in altering the interaction of pathogens with host plants. Therefore, it is useful to characterize the whole effector repertoire of a pathogen to understand the interplay of effectors in plants. Pseudomonas syringae pv. actinidiae is a causal agent of kiwifruit canker disease. In this study, we generated an Agrobacterium -mediated transient expression library of YFP-tagged T3S effectors from two strains of Psa , Psa -NZ V13 and Psa -NZ LV5, in order to gain insight into their mode of action in Nicotiana tabacum and N. benthamiana . Determining the subcellular localization of effectors gives an indication of the possible host targets of effectors. A confocal microscopy assay detecting YFP-tagged Psa effectors revealed that the nucleus, cytoplasm and cell periphery are major targets of Psa effectors. Agrobacterium -mediated transient expression of multiple Psa effectors induced HR-like cell death (HCD) in Nicotiana spp., suggesting that multiple Psa effectors may be recognized by Nicotiana spp.. Virus-induced gene silencing (VIGS) of several known plant immune regulators, EDS1 , NDR1 , or SGT1 specified the requirement of SGT1 in HCD induced by several Psa effectors in N. benthamiana . In addition, the suppression activity of Psa effectors on HCD-inducing proteins and PTI was assessed. Psa effectors showed differential suppression activities on each HCD inducer or PTI. Taken together, our Psa effector repertoire analysis highlights the great diversity of T3S effector functions in planta .

Pseudomonas syringae pv. actinidiae Type III Effectors Localized at Multiple Cellular Compartments Activate or Suppress Innate Immune Responses in Nicotiana benthamiana

PubMed Central

Choi, Sera; Jayaraman, Jay; Segonzac, Cécile; Park, Hye-Jee; Park, Hanbi; Han, Sang-Wook; Sohn, Kee Hoon

2017-01-01

Bacterial phytopathogen type III secreted (T3S) effectors have been strongly implicated in altering the interaction of pathogens with host plants. Therefore, it is useful to characterize the whole effector repertoire of a pathogen to understand the interplay of effectors in plants. Pseudomonas syringae pv. actinidiae is a causal agent of kiwifruit canker disease. In this study, we generated an Agrobacterium-mediated transient expression library of YFP-tagged T3S effectors from two strains of Psa, Psa-NZ V13 and Psa-NZ LV5, in order to gain insight into their mode of action in Nicotiana tabacum and N. benthamiana. Determining the subcellular localization of effectors gives an indication of the possible host targets of effectors. A confocal microscopy assay detecting YFP-tagged Psa effectors revealed that the nucleus, cytoplasm and cell periphery are major targets of Psa effectors. Agrobacterium-mediated transient expression of multiple Psa effectors induced HR-like cell death (HCD) in Nicotiana spp., suggesting that multiple Psa effectors may be recognized by Nicotiana spp.. Virus-induced gene silencing (VIGS) of several known plant immune regulators, EDS1, NDR1, or SGT1 specified the requirement of SGT1 in HCD induced by several Psa effectors in N. benthamiana. In addition, the suppression activity of Psa effectors on HCD-inducing proteins and PTI was assessed. Psa effectors showed differential suppression activities on each HCD inducer or PTI. Taken together, our Psa effector repertoire analysis highlights the great diversity of T3S effector functions in planta. PMID:29326748

Comparative Large-Scale Analysis of Interactions between Several Crop Species and the Effector Repertoires from Multiple Pathovars of Pseudomonas and Ralstonia1[W][OA

PubMed Central

Wroblewski, Tadeusz; Caldwell, Katherine S.; Piskurewicz, Urszula; Cavanaugh, Keri A.; Xu, Huaqin; Kozik, Alexander; Ochoa, Oswaldo; McHale, Leah K.; Lahre, Kirsten; Jelenska, Joanna; Castillo, Jose A.; Blumenthal, Daniel; Vinatzer, Boris A.; Greenberg, Jean T.; Michelmore, Richard W.

2009-01-01

Bacterial plant pathogens manipulate their hosts by injection of numerous effector proteins into host cells via type III secretion systems. Recognition of these effectors by the host plant leads to the induction of a defense reaction that often culminates in a hypersensitive response manifested as cell death. Genes encoding effector proteins can be exchanged between different strains of bacteria via horizontal transfer, and often individual strains are capable of infecting multiple hosts. Host plant species express diverse repertoires of resistance proteins that mediate direct or indirect recognition of bacterial effectors. As a result, plants and their bacterial pathogens should be considered as two extensive coevolving groups rather than as individual host species coevolving with single pathovars. To dissect the complexity of this coevolution, we cloned 171 effector-encoding genes from several pathovars of Pseudomonas and Ralstonia. We used Agrobacterium tumefaciens-mediated transient assays to test the ability of each effector to induce a necrotic phenotype on 59 plant genotypes belonging to four plant families, including numerous diverse accessions of lettuce (Lactuca sativa) and tomato (Solanum lycopersicum). Known defense-inducing effectors (avirulence factors) and their homologs commonly induced extensive necrosis in many different plant species. Nonhost species reacted to multiple effector proteins from an individual pathovar more frequently and more intensely than host species. Both homologous and sequence-unrelated effectors could elicit necrosis in a similar spectrum of plants, suggesting common effector targets or targeting of the same pathways in the plant cell. PMID:19571308

Determinants of lifestyle behavior change to prevent type 2 diabetes in high-risk individuals.

PubMed

den Braver, N R; de Vet, E; Duijzer, G; Ter Beek, J; Jansen, S C; Hiddink, G J; Feskens, E J M; Haveman-Nies, A

2017-06-12

Although there are many effective lifestyle interventions for type 2 diabetes (T2DM) prevention, insight into effective intervention pathways, especially of long-term interventions, is often lacking. This study aims to provide insight into the effective intervention pathways of the SLIMMER diabetes prevention intervention using mediation analyses. In total, 240 participants at increased risk of T2DM were included in the analyses over 18 months. The intervention was a combined lifestyle intervention with a dietary and a physical activity (PA) component. The primary and secondary outcomes were change in fasting insulin (pmol/L) and change in body weight (kg) after 18 months, respectively. Firstly, in a multiple mediator model, we investigated whether significant changes in these outcomes were mediated by changes in dietary and PA behavior. Secondly, in multiple single mediator models, we investigated whether changes in dietary and PA behavior were mediated by changes in behavioral determinants and the participants' psychological profile. The mediation analyses used linear regression models, where significance of indirect effects was calculated with bootstrapping. The effect of the intervention on decreased fasting insulin was 40% mediated by change in dietary and PA behavior, where dietary behavior was an independent mediator of the association (34%). The effect of the intervention on decreased body weight was 20% mediated by change in dietary and PA behavior, where PA behavior was an independent mediator (17%). The intervention significantly changed intake of fruit, fat from bread spread, and fiber from bread. Change in fruit intake was mediated by change in action control (combination of consciousness, self-control, and effort), motivation, self-efficacy, intention, and skills. Change in fat intake was mediated by change in action control and psychological profile. No mediators could be identified for change in fiber intake. The change in PA behavior was mediated by change in action control, motivation, and psychological profile. The effect of the SLIMMER intervention on fasting insulin and body weight was mediated by changes in dietary and PA behavior, in distinct ways. These results indicate that changing dietary as well as PA behavior is important in T2DM prevention.

MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana

PubMed Central

Stiller, Jiri; Davoine, Celine; Björklund, Stefan; Manners, John M.; Kazan, Kemal; Schenk, Peer M.

2017-01-01

The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display down-regulation of genes associated with jasmonate signaling and biosynthesis while up-regulation of salicylic acid associated pathogenesis related genes and reactive oxygen producing and scavenging genes. We propose that MED18 and MED20 form a sub-domain within Mediator that controls the balance of salicylic acid and jasmonate associated defense pathways. PMID:28441405

Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer

PubMed Central

Gai, Wen-Tao; Yu, Da-Peng; Wang, Xin-Sheng; Wang, Pei-Tao

2016-01-01

Ursolic acid is a type of pentacyclic triterpene compound with multiple pharmacological activities including cancer resistance, protection from liver injury, antisepsis, anti-inflammation and antiviral activity. The present study aimed to investigate the anticancer effect of ursolic acid. Ursolic acid activates cell apoptosis and its pro-apoptotic mechanism remains to be fully elucidated. Cell Counting kit-8 assays, flow cytometric analysis and analysis of caspase-3 and caspase-9 activity were used to estimate the anticancer effect of ursolic acid on DU145 prostate cancer cells. The protein expression of cytochrome c, rho-associated protein kinase (ROCK), phosphatase and tensin homolog (PTEN) and cofilin-1 were examined using western blot analysis. In the present study, ursolic acid significantly suppressed cell growth and induced apoptosis, as well as increasing caspase-3 and caspase-9 activities of DU145 cells. Furthermore, cytoplasmic and mitochondrial cytochrome c protein expression was significantly activated and suppressed, respectively, by ursolic acid. Ursolic acid significantly suppressed the ROCK/PTEN signaling pathway and inhibited cofilin-1 protein expression in DU145 cells. The results of the present study indicate that the anticancer effect of ursolic acid activates cell apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer. PMID:27698874

On the (In)Validity of Tests of Simple Mediation: Threats and Solutions

PubMed Central

Pek, Jolynn; Hoyle, Rick H.

2015-01-01

Mediation analysis is a popular framework for identifying underlying mechanisms in social psychology. In the context of simple mediation, we review and discuss the implications of three facets of mediation analysis: (a) conceptualization of the relations between the variables, (b) statistical approaches, and (c) relevant elements of design. We also highlight the issue of equivalent models that are inherent in simple mediation. The extent to which results are meaningful stem directly from choices regarding these three facets of mediation analysis. We conclude by discussing how mediation analysis can be better applied to examine causal processes, highlight the limits of simple mediation, and make recommendations for better practice. PMID:26985234

Post-intervention effects on screen behaviours and mediating effect of parental regulation: the HEalth In Adolescents study – a multi-component school-based randomized controlled trial

PubMed Central

2014-01-01

Background To improve effectiveness of future screen behaviour interventions, one needs to know whether an intervention works via the proposed mediating mechanisms and whether the intervention is equally effective among subgroups. Parental regulation is identified as a consistent correlate of screen behaviours, but prospective evidence as well as the mediation role of parental regulation is largely lacking. This study investigated post-intervention main effects on screen behaviours in the HEIA-intervention – a Norwegian school-based multiple-behaviour study, as well as mediation effects of parental regulation by adolescents’ and parents’ report. In addition, moderating effects of gender and weight status on the intervention and mediating effects were explored. Methods Participating schools were randomized to control (n = 25) or intervention (n = 12) condition. Adolescents (n = 908 Control; 510 Intervention) self-reported their weekday and weekend TV-viewing and computer/game-use. Change in adolescents’ behaviours was targeted through school and parents. Adolescents, mothers (n = 591 Control; 244 Interventions) and fathers (n = 469 Control; 199 Intervention) reported parental regulation of the screen behaviours post-intervention (at 20 month). The product-of-coefficient test using linear regression analysis was conducted to examine main and mediating effects. Results There was no intervention effect on the screen behaviours in the total sample. Gender moderated effect on weekend computer/game-use, while weight status moderated the effect on weekday TV-viewing and computer/game-use. Stratified analyses showed a small favourable intervention effect on weekday TV-viewing among the normal weight. Parental regulation did not mediate change in the screen behaviours. However, stronger parental regulation was associated with less TV-viewing and computer/game-use with effects being conditional on adolescents’ versus parental reports. Parental regulation of the screen behaviours, primarily by the parental report, was associated with change in the respective behaviours. Conclusion Multiple behaviour intervention may not affect all equally well, and the effect may differ by weight status and gender. In future interventions parents should be encouraged to regulate their adolescents’ TV-viewing and computer/game-use on both weekdays and weekends as parental regulation was identified as a determinant of these screen behaviours. However, future intervention studies may need to search for more effective intervention strategies targeting parental regulation. Trial registration Current Controlled Trials ISRCTN98552879 PMID:24568125

Examination of Anxiety Sensitivity and Distress Tolerance as Transdiagnostic Mechanisms Linking Multiple Anxiety Pathologies to Alcohol Use Problems in Adolescents

PubMed Central

Wolitzky-Taylor, Kate; Guillot, Casey R.; Pang, Raina D.; Kirkpatrick, Matthew G.; Zvolensky, Michael J.; Buckner, Julia D.; Leventhal, Adam M.

2015-01-01

Background Multiple forms of anxiety psychopathology are associated with alcohol use problems in adolescents. Yet, the mechanisms underlying this association are unclear. Anxiety sensitivity (AS) and distress tolerance (DT) represent 2 distinct, conceptually relevant transdiagnostic constructs implicated in multiple manifestations of anxiety that may also underlie alcohol use problems and thereby explain why people with anxiety are more likely to have alcohol problems. Methods The current cross-sectional study examined whether AS and DT accounted for (i.e., statistically mediated) the relationship between manifest indicators of the 3 common anxiety phenotypes (generalized anxiety, social anxiety, and panic disorders) and alcohol problems in a sample of 534 high school students (14 to 15 years old). Results Multiple manifestations of anxiety were associated with greater alcohol use problems. AS statistically mediated multiple anxiety–alcohol associations, but DT did not. Conclusions These findings provide preliminary evidence suggesting AS may be an important transdiagnostic target for alcohol prevention programs for those in early adolescence that experience elevated anxiety symptoms. PMID:25706521

Multiple homologous genes knockout (KO) by CRISPR/Cas9 system in rabbit.

PubMed

Liu, Huan; Sui, Tingting; Liu, Di; Liu, Tingjun; Chen, Mao; Deng, Jichao; Xu, Yuanyuan; Li, Zhanjun

2018-03-20

The CRISPR/Cas9 system is a highly efficient and convenient genome editing tool, which has been widely used for single or multiple gene mutation in a variety of organisms. Disruption of multiple homologous genes, which have similar DNA sequences and gene function, is required for the study of the desired phenotype. In this study, to test whether the CRISPR/Cas9 system works on the mutation of multiple homologous genes, a single guide RNA (sgRNA) targeting three fucosyltransferases encoding genes (FUT1, FUT2 and SEC1) was designed. As expected, triple gene mutation of FUT1, FUT2 and SEC1 could be achieved simultaneously via a sgRNA mediated CRISPR/Cas9 system. Besides, significantly reduced serum fucosyltransferases enzymes activity was also determined in those triple gene mutation rabbits. Thus, we provide the first evidence that multiple homologous genes knockout (KO) could be achieved efficiently by a sgRNA mediated CRISPR/Cas9 system in mammals, which could facilitate the genotype to phenotype studies of homologous genes in future. Copyright © 2018 Elsevier B.V. All rights reserved.

Moral distress and burnout syndrome: are there relationships between these phenomena in nursing workers?

PubMed

Dalmolin, Graziele de Lima; Lunardi, Valéria Lerch; Lunardi, Guilherme Lerch; Barlem, Edison Luiz Devos; Silveira, Rosemary Silva da

2014-01-01

to identify relationships between moral distress and Burnout in the professional performance from the perceptions of the experiences of nursing workers. this is a survey type study with 375 nursing workers working in three different hospitals of southern Rio Grande do Sul, with the application of adaptations of the Moral Distress Scale and the Maslach Burnout Inventory, validated and standardized for use in Brazil. Data validation occurred through factor analysis and Cronbach's alpha. For the data analysis bivariate analysis using Pearson's correlation and multivariate analysis using multiple regression were performed. the existence of a weak correlation between moral distress and Burnout was verified. A possible positive correlation between Burnout and therapeutic obstinacy, and a negative correlation between professional fulfillment and moral distress were identified. the need was identified for further studies that include mediating and moderating variables that may explain more clearly the models studied.

Moral distress and Burnout syndrome: are there relationships between these phenomena in nursing workers?1

PubMed Central

Dalmolin, Graziele de Lima; Lunardi, Valéria Lerch; Lunardi, Guilherme Lerch; Barlem, Edison Luiz Devos; da Silveira, Rosemary Silva

2014-01-01

Objective to identify relationships between moral distress and Burnout in the professional performance from the perceptions of the experiences of nursing workers. Methods this is a survey type study with 375 nursing workers working in three different hospitals of southern Rio Grande do Sul, with the application of adaptations of the Moral Distress Scale and the Maslach Burnout Inventory, validated and standardized for use in Brazil. Data validation occurred through factor analysis and Cronbach's alpha. For the data analysis bivariate analysis using Pearson's correlation and multivariate analysis using multiple regression were performed. Results the existence of a weak correlation between moral distress and Burnout was verified. A possible positive correlation between Burnout and therapeutic obstinacy, and a negative correlation between professional fulfillment and moral distress were identified. Conclusion the need was identified for further studies that include mediating and moderating variables that may explain more clearly the models studied. PMID:24553701

Mediational Links Among Parenting Styles, Perceptions of Parental Confidence, Self-Esteem, and Depression on Alcohol-Related Problems in Emerging Adulthood*

PubMed Central

Patock-Peckham, Julie A.; Morgan-Lopez, Antonio A.

2009-01-01

Objective: Depression is often found to be comorbid with alcohol-related problems. Parental overprotection, which may be of particular importance during emerging adulthood, has been linked to internalizing symptoms in offspring. This article evaluates the impact of parenting styles and parental confidence in their offspring on an internalizing pathway to alcohol-related problems through self-esteem and depression. Method: Mediational links were tested among parenting styles (authoritative, authoritarian, permissive), parental confidence (overprotection, autonomy), self-esteem, depression, and alcohol-related problems. A two-group, multiple indicator multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. Results: Overall, having a father who was confident in his child's ability to make autonomous decisions was protective against depression for both genders. Perceptions of paternal autonomy mediated the impact of the fathers' parenting styles (authoritative, permissive) on depression for both genders. For men, parental overprotection mediated the impact of an authoritarian father on self-esteem, and self-esteem mediated the impact of parental overprotection on depression. Moreover, among men, perceptions of maternal autonomy mediated the impact of the mothers' parenting styles (authoritative, permissive) on self-esteem, and self-esteem mediated the impact of maternal autonomy on depression. Conclusions: The current pattern of findings is distinct from pathways through behavioral undercontrol with influences from the same-sex parent for both genders. These findings indicate that parenting may have differential influences on internalizing pathways to alcohol-related problems. PMID:19261233

Filipino Americans and racism: A multiple mediation model of coping.

PubMed

Alvarez, Alvin N; Juang, Linda P

2010-04-01

Although the literature on Asian Americans and racism has been emerging, few studies have examined how coping influences one's encounters with racism. To advance the literature, the present study focused on the psychological impact of Filipino Americans' experiences with racism and the role of coping as a mediator using a community-based sample of adults (N = 199). Two multiple mediation models were used to examine the mediating effects of active, avoidance, support-seeking, and forbearance coping on the relationship between perceived racism and psychological distress and self-esteem, respectively. Separate analyses were also conducted for men and women given differences in coping utilization. For men, a bootstrap procedure indicated that active, support-seeking, and avoidance coping were mediators of the relationship between perceived racism and psychological distress. Active coping was negatively associated with psychological distress, whereas both support seeking and avoidance were positively associated with psychological distress. A second bootstrap procedure for men indicated that active and avoidance coping mediated the relationship between perceived racism and self-esteem such that active coping was positively associated with self-esteem, and avoidance was negatively associated with self-esteem. For women, only avoidance coping had a significant mediating effect that was associated with elevations in psychological distress and decreases in self-esteem. The results highlight the importance of examining the efficacy of specific coping responses to racism and the need to differentiate between the experiences of men and women. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Mediational links among parenting styles, perceptions of parental confidence, self-esteem, and depression on alcohol-related problems in emerging adulthood.

PubMed

Patock-Peckham, Julie A; Morgan-Lopez, Antonio A

2009-03-01

Depression is often found to be comorbid with alcohol-related problems. Parental overprotection, which may be of particular importance during emerging adulthood, has been linked to internalizing symptoms in offspring. This article evaluates the impact of parenting styles and parental confidence in their offspring on an internalizing pathway to alcohol-related problems through self-esteem and depression. Mediational links were tested among parenting styles (authoritative, authoritarian, permissive), parental confidence (overprotection, autonomy), self-esteem, depression, and alcohol-related problems. A two-group, multiple indicator multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. Overall, having a father who was confident in his child's ability to make autonomous decisions was protective against depression for both genders. Perceptions of paternal autonomy mediated the impact of the fathers' parenting styles (authoritative, permissive) on depression for both genders. For men, parental overprotection mediated the impact of an authoritarian father on self-esteem, and self-esteem mediated the impact of parental overprotection on depression. Moreover, among men, perceptions of maternal autonomy mediated the impact of the mothers' parenting styles (authoritative, permissive) on self-esteem, and self-esteem mediated the impact of maternal autonomy on depression. The current pattern of findings is distinct from pathways through behavioral undercontrol with influences from the same-sex parent for both genders. These findings indicate that parenting may have differential influences on internalizing pathways to alcohol-related problems.

Robust Mediation Analysis Based on Median Regression

PubMed Central

Yuan, Ying; MacKinnon, David P.

2014-01-01

Mediation analysis has many applications in psychology and the social sciences. The most prevalent methods typically assume that the error distribution is normal and homoscedastic. However, this assumption may rarely be met in practice, which can affect the validity of the mediation analysis. To address this problem, we propose robust mediation analysis based on median regression. Our approach is robust to various departures from the assumption of homoscedasticity and normality, including heavy-tailed, skewed, contaminated, and heteroscedastic distributions. Simulation studies show that under these circumstances, the proposed method is more efficient and powerful than standard mediation analysis. We further extend the proposed robust method to multilevel mediation analysis, and demonstrate through simulation studies that the new approach outperforms the standard multilevel mediation analysis. We illustrate the proposed method using data from a program designed to increase reemployment and enhance mental health of job seekers. PMID:24079925

Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma

PubMed Central

Vasir, Baldev; Uhl, Lynne; Blotta, Simona; MacNamara, Claire; Somaiya, Poorvi; Wu, Zekui; Joyce, Robin; Levine, James D.; Dombagoda, Dilani; Yuan, Yan Emily; Francoeur, Karen; Fitzgerald, Donna; Richardson, Paul; Weller, Edie; Anderson, Kenneth; Kufe, Donald; Munshi, Nikhil; Avigan, David

2011-01-01

We have developed a tumor vaccine in which patient-derived myeloma cells are chemically fused with autologous dendritic cells (DCs) such that a broad spectrum of myeloma-associated antigens are presented in the context of DC-mediated costimulation. We have completed a phase 1 study in which patients with multiple myeloma underwent serial vaccination with the DC/multiple myeloma fusions in conjunction with granulocyte-macrophage colony-stimulating factor. DCs were generated from adherent mononuclear cells cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-α and fused with myeloma cells obtained from marrow aspirates. Vaccine generation was successful in 17 of 18 patients. Successive cohorts were treated with 1 × 106, 2 × 106, and 4 × 106 fusion cells, respectively, with 10 patients treated at the highest dose level. Vaccination was well tolerated, without evidence of dose-limiting toxicity. Vaccination resulted in the expansion of circulating CD4 and CD8 lymphocytes reactive with autologous myeloma cells in 11 of 15 evaluable patients. Humoral responses were documented by SEREX (Serologic Analysis of Recombinant cDNA Expression Libraries) analysis. A majority of patients with advanced disease demonstrated disease stabilization, with 3 patients showing ongoing stable disease at 12, 25, and 41 months, respectively. Vaccination with DC/multiple myeloma fusions was feasible and well tolerated and resulted in antitumor immune responses and disease stabilization in a majority of patients. PMID:21030562

Parental Depression and Child Cognitive Vulnerability Predict Children’s Cortisol Reactivity

PubMed Central

Hayden, Elizabeth P.; Hankin, Benjamin L.; Mackrell, Sarah V.M.; Sheikh, Haroon I.; Jordan, Patricia L.; Dozois, David J.A.; Singh, Shiva M.; Olino, Thomas M.; Badanes, Lisa S.

2015-01-01

Risk for depression is expressed across multiple levels of analysis. For example, parental depression and cognitive vulnerability are known markers of depression risk, but no study has examined their interactive effects on children’s cortisol reactivity, a likely mediator of early depression risk. We examined relations across these different levels of vulnerability using cross-sectional and longitudinal methods in two community samples of children. Children were assessed for cognitive vulnerability using self-reports (Study 1; n = 244) and tasks tapping memory and attentional bias (Study 2; n = 205), and their parents were assessed for depression history using structured clinical interviews. In both samples, children participated in standardized stress tasks and cortisol reactivity was assessed. Cross-sectionally and longitudinally, parental depression history and child cognitive vulnerability interacted to predict children’s cortisol reactivity; specifically, associations between parent depression and elevated child cortisol activity were found when children also showed elevated depressotypic attributions, as well as attentional and memory biases. Findings indicate that models of children’s emerging depression risk may benefit from the examination of the interactive effects of multiple sources of vulnerability across levels of analysis. PMID:25422972

Programmable and Multiparameter DNA-Based Logic Platform For Cancer Recognition and Targeted Therapy

PubMed Central

2014-01-01

The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention. With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable. As a trial to accomplish this, we have recently designed a DNA-based device that is capable of performing autonomous logic-based analysis of two or three cancer cell-surface markers. Combining the specific target-recognition properties of DNA aptamers with toehold-mediated strand displacement reactions, multicellular marker-based cancer analysis can be realized based on modular AND, OR, and NOT Boolean logic gates. Specifically, we report here a general approach for assembling these modular logic gates to execute programmable and higher-order profiling of multiple coexisting cell-surface markers, including several found on cancer cells, with the capacity to report a diagnostic signal and/or deliver targeted photodynamic therapy. The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy. PMID:25361164