104 resultados para mediators


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The aim of this cross-sectional study was to identify individual, social, and environmental contributors (mediators) to individual- and area-level differences in leisure-time physical activity across socio-economic groups. A two-stage stratified sampling design was used to recruit 20–65 year old adults (N = 2194) living in 154 census collection districts of Adelaide, Australia (overall response rate: 12%). Participants completed two surveys six months apart (response rate on the second survey: 83%). Individual-level socio-economic status (SES) was assessed using self-report measures on educational attainment, household income, and household size. Area-level SES was assessed using census data on median household income and household size for each selected census district. Bootstrap generalized linear models were used to examine associations between SES, potential mediators, and leisure-time physical activity. The product-of-coefficient test was used to estimate mediating effects. All SES measures were independently associated with potential individual and social mediators of the SES-activity relationships. Individual- and area-level income was also associated with perceived neighborhood attributes. Self-efficacy and social support for physical activity explained virtually all of the differences in physical activity across educational attainment groups. Physical barriers to walking and access to public open space contributed in part to the explanation of differences in recreational walking across income groups. Yet, self-efficacy and social support were the key mediators of the observed relationships between individual- and area-level income and physical activity. This study suggests that in order to increase physical activity participation in the more disadvantaged segments of the population, comprehensive, multilevel interventions targeting activity-related attitudes and skills as well as social and physical environments are needed.

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Although CD8+ T cells do not contribute to protection against the blood stage of Plasmodium infection, there is mounting evidence that they are principal mediators of murine experimental cerebral malaria (ECM). At present, there is no direct evidence that the CD8+ T cells mediating ECM are parasite-specific or, for that matter, whether parasite-specific CD8+ T cells are generated in response to blood-stage infection. To resolve this and to define the cellular requirements for such priming, we generated transgenic P. berghei parasites expressing model T cell epitopes. This approach was necessary as MHC class I-restricted antigens to blood-stage infection have not been defined. Here, we show that blood-stage infection leads to parasite-specific CD8+ and CD4+ T cell responses. Furthermore, we show that P. berghei-expressed antigens are cross-presented by the CD8α+ subset of dendritic cells (DC), and that this induces pathogen-specific cytotoxic T lymphocytes (CTL) capable of lysing cells presenting antigens expressed by blood-stage parasites. Finally, using three different experimental approaches, we provide evidence that CTL specific for parasite-expressed antigens contribute to ECM.

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Television (TV) viewing is the dominant recreational pastime at all ages, especially for children and adolescents. Many studies have shown that higher TV viewing hours are associated with higher body mass index (BMI), lower levels of fitness and higher blood cholesterol levels. Although the effect size estimated from observational studies is small (with TV viewing explaining very little of the variance in BMI), the results of intervention studies show large effect sizes. The potential mediators of the effect of higher TV viewing on higher BMI include less time for physical activity, reduced resting metabolic rate (for which there is little supporting evidence) and increased energy intake (from more eating while watching TV and a greater exposure to marketing of energy dense foods). Electronic games may have an effect on unhealthy weight gain, but are less related to increased energy intake and their usage is relatively new, making effect size difficult to determine. Thus, TV viewing does not explain much of the differences in body size between individuals or the rise in obesity over time, perhaps because of the uniformly high, but relatively stable, TV viewing hours. Reducing TV viewing hours is a difficult prospect because potential actions, such as social marketing and education, are likely to be relatively weak interventions, although the evidence would suggest that, if viewing could be reduced, it could have a significant impact on reducing obesity prevalence. Regulations to reduce the heavy marketing of energy dense foods and beverages on TV may be the most effective public health measure available to minimize the impact of TV viewing on unhealthy weight gain.

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Despite research findings demonstrating a relationship between dissociation and binge eating, the psychological processes that may underlie this association remain unclear. The present study examined 2 potential explanations: (a) that dissociation disinhibits behavioral control over eating and (b) that dissociation interferes with self-awareness and undermines body image. A total of 151 female university students completed measures of dissociation, body dissatisfaction, impulsivity, internalization of the thin ideal, body comparison, and binge eating. Correlations confirmed the presence of a relationship between dissociation and binge eating, and regression analyses revealed that this relationship is limited to body-specific (somatic) symptoms of dissociation. Path analyses identified body dissatisfaction, comparison, and impulsivity as significant mediators of this relationship. However, inclusion of all 3 mediated paths in a full model revealed that only body dissatisfaction is a unique mediator. The relevance of somatic symptoms, and the unique contribution of body dissatisfaction as a mediator, are consistent with an explanation of the relationship between dissociation and binge eating that is based on a vulnerability of body image. The results emphasize the need for future research to consider the relation of dissociation to a broader range of disordered eating symptoms than simply binge eating.

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Objective: To examine the relationship between overweight/obesity in children, socioeconomic status and ethnicity/cultural background.

Design: Cross-sectional survey of children aged 4–13 years.

Setting: A total of 23 primary (elementary) schools in an inner urban municipality of Melbourne, Australia.

Participants: A total of 2685 children aged 4–13 years and their parents.

Main exposure measures: Ethnicity/cultural background – maternal region of birth; socioeconomic position (SEP) indicators – maternal and paternal educational attainment, family employment status, possession of a healthcare card, ability to buy food, indicator of disadvantage (Socioeconomic Index for Areas, SEIFA) score for school; parental weight status.

Main outcome measure: Prevalence of overweight/obesity.

Results: Prevalence of overweight/obesity approached 1 in 3 (31%) in this sample. Prevalence of overweight/obesity was greater for children of both North Africa and Middle Eastern background and children of Southern, South Eastern and Eastern European background compared with children of Australian background. This difference remained after adjusting for age, sex, height, clustering by school, SEP indicators and parental weight status; odds ratio, OR=1.57 (95% confidence interval, CI 1.12–2.19) and 1.88 (95%CI 1.24–2.85), respectively.

Conclusions: There is a clear independent effect of ethnicity above and beyond the effect of socioeconomic status on overweight and obesity in children. Further research is required to explore the mediators of this gradient.

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Objectives : To evaluate the effectiveness of an intervention to prevent excess weight gain, reduce time spent in screen behaviours, promote participation in and enjoyment of physical activity (PA), and improve fundamental movement skills among children.

Participants : In 2002, 311 children (78% response; 49% boys), average age 10 years 8 months, were recruited from three government schools in low socioeconomic areas of Melbourne, Australia.

Design : Group-randomized controlled trial. Children were randomized by class to one of the four conditions: a behavioural modification group (BM; n=66); a fundamental movement skills group (FMS; n=74); a combined BM/FMS group (BM/FMS; n=93); and a control (usual curriculum) group (n=62). Data were collected at baseline, post intervention, 6- and 12-month follow-up periods.

Results : BMI data were available for 295 children at baseline and 268 at 12-month follow-up. After adjusting for food intake and PA, there was a significant intervention effect from baseline to post intervention on age- and sex-adjusted BMI in the BM/FMS group compared with controls (-1.88 kg m-2, P<0.01), which was maintained at 6- and 12-month follow-up periods (-1.53 kg m-2, P<0.05). Children in the BM/FMS group were less likely than controls to be overweight/obese between baseline and post intervention (adjusted odds ratio (AOR)=0.36, P<0.05); also maintained at 12-month follow-up (AOR=0.38, P<0.05). Compared with controls, FMS group children recorded higher levels and greater enjoyment of PA; and BM children recorded higher levels of PA and TV viewing across all four time points. Gender moderated the intervention effects for participation in and enjoyment of PA, and fundamental movement skills.

Conclusion :
This programme represents a promising approach to preventing excess weight gain and promoting participation in and enjoyment of PA. Examination of the mediators of this intervention and further tailoring of the programme to suit both genders is required.

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Background: Members of the protein kinase C (PKC) family are key signalling mediators in immune responses, and pharmacological inhibition of PKCs may be useful for treating immune-mediated diseases. Objective: To review and discuss the insights gained so far into various PKC isozymes and the therapeutic potential and challenges of developing PKC inhibitors for immune disorder therapy. Methods: A literature review of the role of PKCs in immune cell signalling and recent studies describing immune functions associated with PKC isozyme deficiency in relevant mouse disease models, followed by specific case studies of current and potential therapeutic strategies targeting PKCs. Results/conclusion: There is vast amount of data supporting PKC isozymes as attractive drug targets for certain immune disorders. Although the development of specific PKC isozyme inhibitors has been challenging, some progress has been made. It remains to be seen if broad-scale or isozyme-selective inhibition of PKC will have clinical efficacy.

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Stress responses are thought to act within the hypothalamopituitary unit to impair the reproductive system, and the sites of action may differ between sexes. The effect of isolation and restraint stress on pituitary responsiveness to GnRH in sheep was investigated, with emphasis on possible sex differences. Experiments were conducted during the breeding season and the nonbreeding season. In both experiments, 125 ng of GnRH was injected i.v. every 2 h into hypothalamopituitary disconnected, gonadectomized rams and ewes on 3 experimental days, with each day divided into two periods. During the second period on Day 2, isolation and restraint stress was imposed for 5.5 h. Plasma concentrations of LH and cortisol were measured in samples of blood collected from the jugular vein. In the second experiment (nonbreeding season), plasma concentrations of epinephrine, norepinephrine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylglycol were also measured. In both experiments, there was no effect of isolation and restraint stress on plasma concentrations of cortisol in either sex. During the breeding season, there was no effect of isolation and restraint stress on plasma concentrations of LH in either sex. During the nonbreeding season, the amplitude of the first LH pulse after the commencement of stress was significantly reduced (P < 0.05) in rams and ewes. In the second experiment, during stress there was a significant increase (P < 0.05) in plasma concentrations of epinephrine in rams and ewes and significantly higher (P < 0.05) basal concentrations of norepinephrine in ewes than in rams. These results suggest that in sheep stress reduces responsiveness of the pituitary gland to exogenous GnRH during the nonbreeding season but not during the breeding season, possibly because of mediators of the stress response other than those of the hypothalamus-pituitary-adrenal gland axis.

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This thesis reports on research examining the habituation of emotional variables to filmed violence. The following subjective emotional variables were assessed: positive feelings, anxiety, disgust, entertainment and anger. In addition, an objective measure of emotional response was recorded physiologically, using the startle eyeblink response. The mediating influence of personality, individual differences and contextual features on an individuals’ perception of and reaction to filmed violence were also explored. Study one was exploratory in nature served to identify and select the film stimuli to be employed in the subsequent studies. The primary aim of the study was to allow for the identification of violent stimuli considered to be most socially and culturally relevant. The present research builds on existing scientific literature which has began to appreciate that differences in the context of a portrayal holds important implications for its impact on viewers. Thus, a secondary and more specific desire of study one was to obtain an evaluation of the contextual features of the violent film segments. A sample of 30 participants viewed and rated the film stimuli on the variables of realism, fantasy and violence. From this exploratory study four violent film stimuli were subsequently employed. Study 2 used the eyeblink startle response proposed by Vrana, Spence and Lang (1988) to explore the habituation of emotional variables to a realistic depiction of filmed violence. Emotional response was assessed both objectively, using the eyeblink startle response and subjectively through individuals self-reports. In addition the study investigated the significance of individual differences as mediators of emotional response. Questionnaire and physiological data were obtained from 30 participants. Overall, repeated exposure to filmed violence resulted in a decline in both objective and subjective emotional response. Differences were identified in the manner in which men and women responded to the film. Women reacted initially and over time with more intense physiological and psychological reactions to the violent film than males. Specifically, men displayed more curiosity and reported greater entertainment and positive feelings in response to the film, whilst women found the violence more disgusting and reported higher levels of anger and anxiety. It was found that the eyeblink startle magnitude paralleled the subjective emotional processing of the violent film, thus providing further confirmatory evidence of its validity in the investigation of emotional reactions to a stimulus. Personality factors were found to mediate emotional response to filmed violence, with neuroticism most powerfully implicated. High levels of neuroticism were found to be associated with greater anger and anxiety and less positive feelings whilst viewing violent film. A high score on extraversion was correlated with higher levels of anger and lower levels of curiosity and entertainment. Whilst the aims of study 3 were identical to that of study 2, a variation in the contextual feature of the violent film stimuli under investigation was the distinguishing and pertinent feature. Study 2 provided data on the habituation of emotional response to a realistic depiction of filmed violence. Study 3 was concerned with emotional response over repeated exposure to a fantasized violent depiction. Therefore, allowing for a comparison regarding the effects of context on emotional response. The results of study 3, with respect to habituation of emotional response, personality and individual differences, were similar to that obtained in study 2. A comparison of the two studies, however, revealed that individuals responded significantly different to the contextual features of the violent portrayal. Compared to the fantasised portrayal the realistic film stimulus was reported to be more digusting, anxiety provoking and less entertaining. In addition, and not surprisingly respondents reported that the realistic portrayal resulted in the production of more anger and less positive feelings.

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1.      Skeletal muscle oxidative function and metabolic gene expression are co-ordinately downregulated in metabolic diseases such as insulin resistance, obesity and Type 2 diabetes. Altering skeletal muscle metabolic gene expression to favour enhanced energy expenditure is considered a potential therapy to combat these diseases.

2.      Histone deacetylases (HDACs) are chromatin-remodelling enzymes that repress gene expression. It has been shown that HDAC4 and 5 co-operatively regulate a number of genes involved in various aspects of metabolism. Understanding how HDACs are regulated provides insights into the mechanisms regulating skeletal muscle metabolic gene expression.

3.      Multiple kinases control phosphorylation-dependent nuclear export of HDACs, rendering them unable to repress transcription. We have found a major role for the AMP-activated protein kinase (AMPK) in response to energetic stress, yet metabolic gene expression is maintained in the absence of AMPK activity. Preliminary evidence suggests a potential role for protein kinase D, also a Class IIa HDAC kinase, in this response.

4.      The HDACs are also regulated by ubiquitin-mediated proteasomal degradation, although the exact mediators of this process have not been identified.

5.      Because HDACs appear to be critical regulators of skeletal muscle metabolic gene expression, HDAC inhibition could be an effective therapy to treat metabolic diseases.

6.      Together, these data show that HDAC4 and 5 are critical regulators of metabolic gene expression and that understanding their regulation could provide a number of points of intervention for therapies designed to treat metabolic diseases, such as insulin resistance, obesity and Type 2 diabetes.

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Focusing on novels written since 1980 by Australian authors Rodney Hall, Liam Davison, Tim Winton, Elizabeth Jolley and Gerald Murnane, and engaging with responses to the land by visual and performing artists, this thesis explores the idea that the writer and artist are mediators in the multitude of experiences that constitutes landscape.

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Seasonal influenza virus infection is a leading cause of illness and mortality in young children and the elderly each year. Current influenza vaccines generate protective antibody responses; however, these must be given annually to provide protection against serologically distinct viruses. By contrast, CD8.sup.+ T cells are capable of recognizing conserved antigenic determinants within the influenza virion and, as such, may provide protection against a number of variant strains of the virus. CD8.sup.+ T cells play a critical key role in controlling and resolving influenza virus infections via the production of cytokines and cytolytic mediators. This article focuses on the induction of the influenza-specific CD8.sup.+ T-cell response and how these cells acquire and maintain effector function after induction. Moreover, we discuss how cytotoxic T-lymphocyte function correlates with protection following vaccination.

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Adolescents of low socio-economic position (SEP) are less likely than those of higher SEP to consume diets in line with current dietary recommendations. The reasons for these SEP variations remain poorly understood. We investigated the mechanisms underlying socio-economic variations in adolescents’ eating behaviours using a theoretically derived explanatory model. Data were obtained from a community-based sample of 2529 adolescents aged 12–15 years, from 37 secondary schools in Victoria, Australia. Adolescents completed a web-based survey assessing their eating behaviours, self-efficacy for healthy eating, perceived importance of nutrition and health, social modelling and support and the availability of foods in the home. Parents provided details of maternal education level, which was used as an indicator of SEP. All social cognitive constructs assessed mediated socio-economic variations in at least one indicator of adolescents’ diet. Cognitive factors were the strongest mediator of socio-economic variations in fruit intakes, while for energy-dense snack foods and fast foods, availability of energy-dense snacks at home tended to be strong mediators. Social cognitive theory provides a useful framework for understanding socio-economic variations in adolescent's diet and might guide public health programmes and policies focusing on improving adolescent nutrition among those experiencing socio-economic disadvantage.

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Objective. To explore the association between home environmental variables and television (TV) time, and the mediating pathways underlying this association.

Methods. The current study used data from the longitudinal ENDORSE study. Self-reported data was available for 1 265 adolescents (mean age of 12–15 years at baseline) on home environment (availability of a TV in the bedroom, perceived parental modelling, family rules), potential mediators (intention, attitude, perceived behavioural control, subjective norm towards TV viewing) and TV viewing time. Mediation analyses were conducted using General Estimating Equations and mediation effects were calculated as the product-of-coefficients.

Results.
Significant overall positive associations were found for the presence of a TV in the bedroom and parental modelling with self-reported TV viewing. Controlling family rules showed an inverse association with reported TV time. Similarly, parental modelling and a TV in the bedroom were significantly positively associated with the Theory of Planned Behaviour variables and habit strength, while family rules showed an inverse association with these potential mediators. In turn, most potential mediators were positively associated with TV viewing. Intention, attitude and habit strength were the strongest mediators in all three associations explaining more than 55% of the overall association. Habit strength alone explained 38.2%–58.0% of the overall associations.

Conclusions. Home and family environmental predictors of TV time among adolescents may be strongly mediated by habit strength and other personal factors. Future intervention studies should explore if changes in home and family environments indeed lead to reductions in TV time through these mediators.

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Objective The Dutch Obesity Intervention in Teenagers (DOiT) is a school-based randomised controlled trial that was effective in decreasing the consumption of sugar-sweetened beverages among adolescents. The present study examined, using mediation analysis, whether this decrease in consumption of sugar-sweetened beverages could be explained by an increase in the consumption of water or diet drinks.

Design Participants completed a questionnaire about their beverage consumption at baseline and at 8 months (immediately post-intervention), 12- and 20-month follow-ups. A series of multi-level linear regression analyses were performed to examine water and diet drink consumption as potential mediators of the intervention effect on the consumption of sugar-sweetened beverages.

Setting Eighteen Dutch secondary schools.

Subjects
A total of 747 adolescents (mean age: 12·7 years).

Results
In addition to the DoiT intervention effect of a reduction in the consumption of sugar-sweetened beverages at 8 months (−284 ml/d; 95 % CI −420, −148) and 12 months (−260 ml/d; 95 % CI −360, −160), there was also a significant reduction in diet drinks at 8 months (−52 ml/d; 95 % CI −89, −16). There was no significant difference in water consumption at any follow-up. The decrease in sugar-sweetened beverage consumption could not be explained by an increase in water or diet drink consumption at any time point.

Conclusions Interventions aimed at reducing sugar-sweetened beverage consumption may be effective without changing consumption of other beverages. Reducing sugar-sweetened beverages was, however, a main message of the DOiT intervention. It is possible that a concomitant promotion of water may have resulted in a greater increase in water intake and replacement of sugar-sweetened beverages with water.