Review of 100% in control: Report to Public Health Services, Queensland Health

Report reviews the Queensland 100% IN CONTROL campaign, the alcohol, tobacco and other drug prevention campaign directed at young people 12 - 17 years. Methodology integrates information from a systematic literature review, the views of young people and other stakeholders, data on patterns of substance use, and campaign evaluations. Strategic policy scenarios are advanced to inform future directions

Adaptor SKAP-55 Binds p21ras Activating Exchange Factor RasGRP1 and Negatively Regulates the p21ras-ERK Pathway in T-Cells

While the adaptor SKAP-55 mediates LFA-1 adhesion on T-cells, it is not known whether the adaptor regulates other aspects of signaling. SKAP-55 could potentially act as a node to coordinate the modulation of adhesion with downstream signaling. In this regard, the GTPase p21ras and the extracellular signal-regulated kinase (ERK) pathway play central roles in T-cell function. In this study, we report that SKAP-55 has opposing effects on adhesion and the activation of the p21ras -ERK pathway in T-cells. SKAP-55 deficient primary T-cells showed a defect in LFA-1 adhesion concurrent with the hyper-activation of the ERK pathway relative to wild-type cells. RNAi knock down (KD) of SKAP-55 in T-cell lines also showed an increase in p21ras activation, while over-expression of SKAP-55 inhibited activation of ERK and its transcriptional target ELK. Three observations implicated the p21ras activating exchange factor RasGRP1 in the process. Firstly, SKAP-55 bound to RasGRP1 via its C-terminus, while secondly, the loss of binding abrogated SKAP-55 inhibition of ERK and ELK activation. Thirdly, SKAP-55−/− primary T-cells showed an increased presence of RasGRP1 in the trans-Golgi network (TGN) following TCR activation, the site where p21ras becomes activated. Our findings indicate that SKAP-55 has a dual role in regulating p21ras-ERK pathway via RasGRP1, as a possible mechanism to restrict activation during T-cell adhesion

Regulation of RasGRP1 Function in T Cell Development and Activation by Its Unique Tail Domain

The Ras-guanyl nucleotide exchange factor RasGRP1 plays a critical role in T cell receptor-mediated Erk activation. Previous studies have emphasized the importance of RasGRP1 in the positive selection of thymocytes, activation of T cells, and control of autoimmunity. RasGRP1 consists of a number of well-characterized domains, which it shares with its other family members; however, RasGRP1 also contains an ∼200 residue-long tail domain, the function of which is unknown. To elucidate the physiological role of this domain, we generated knock-in mice expressing RasGRP1 without the tail domain. Further analysis of these knock-in mice showed that thymocytes lacking the tail domain of RasGRP1 underwent aberrant thymic selection and, following TCR stimulation, were unable to activate Erk. Furthermore, the deletion of the tail domain led to enhanced CD4+ T cell expansion in aged mice, as well as the production of autoantibodies. Mechanistically, the tail-deleted form of RasGRP1 was not able to traffic to the cell membrane following stimulation, indicating a potential reason for its inability to activate Erk. While the DAG-binding C1 domain of RasGRP1 has long been recognized as an important factor mediating Erk activation, we have revealed the physiological relevance of the tail domain in RasGRP1 function and control of Erk signaling

Impact of flavonoid-rich black tea and beetroot juice on postprandial peripheral vascular resistance and glucose homeostasis in obese, insulin-resistant men: a randomized controlled trial.

BACKGROUND: Insulin-stimulated muscle blood flow facilitates plasma glucose disposal after a meal, a mechanism that is impaired in obese, insulin-resistant volunteers. Nitrate- or flavonoid-rich products, through their proposed effects on nitric oxide, may improve postprandial blood flow and, subsequently, glucose disposal. To investigate whether a single dose of nitrate-rich beetroot juice or flavonoid-rich black tea lowers postprandial muscle vascular resistance in obese volunteers and alters postprandial glucose or insulin concentrations. METHOD: In a randomised, controlled, cross-over study, 16 obese, insulin-resistant males consumed 75 g glucose, which was combined with 100 ml black tea, beetroot juice or control (water). Peripheral vascular resistance (VR), calculated as mean arterial pressure divided by blood flow, was assessed in the arm and leg conduit arteries, resistance arteries and muscle microcirculation across 3 h (every 30-min) after the oral glucose load. RESULTS: During control, we found no postprandial response in VR in conduit, resistance and microvessels (all P > 0.05). Black tea decreased VR compared to control in conduit, resistance and microvessels (all P < 0.05). Beetroot juice decreased postprandial VR in resistance vessels, but not in conduit artery and microvessels. Although postprandial glucose response was similar after all interventions, postprandial insulin response was attenuated by ~29 % after tea (P < 0.0005), but not beetroot juice. CONCLUSIONS: A single dose of black tea decreased peripheral VR across upper and lower limbs after a glucose load which was accompanied by a lower insulin response. Future studies in insulin-resistant subjects are warranted to confirm the observed effects and to explore whether long-term regular tea consumption affects glucose homeostasis. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov on 30(th) November 2012 (NCT01746329)

Living with diabetes: rationale, study design and baseline characteristics for an Australian prospective cohort study

Background: Diabetes mellitus is a major global public health threat. In Australia, as elsewhere, it is responsible for a sizeable portion of the overall burden of disease, and significant costs. The psychological and social impact of diabetes on individuals with the disease can be severe, and if not adequately addressed, can lead to the worsening of the overall disease picture. The Living With Diabetes Study aims to contribute to a holistic understanding of the psychological and social aspects of diabetes mellitus

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

An investigation of the relationship between body image and self-concept in adolescent females : a developmental perspective

The research programme detailed in this thesis examined body image and self-concept in adolescent females. 804 young women in years 7 through 12, from two private, denominational, single sex metropolitan schools, completed the Self Description Questionnaire II (SDQ II; Marsh, 1992), a multidimensional measure of self-concept, and several measures of body image including the Body Esteem Scale (BES-1; Mendelson & White, 1982), the Body Attitudes Questionnaire (BAQ; Ben-Tovim & Walker, 1991), the Figure Rating Scale (FRS; Stunkard, Sorenson, & Schulsinger, 1983) and the Body Esteem Scale (BES-2; Franzoi & Shields, 1984). In addition, a subsample of 24 young women, 8 from each of three year levels, 8, 10 and 12, were involved a single, individual semi-structured interview to obtain their views on body image, its development and its relationship to self-concept. The responses to the questionnaires were examined in two ways. Descriptive analyses were performed on the subscales of the self-concept and body image measures for age groupings and school year levels. In addition, the responses were involved in multiple regression analyses to identify significant body image predictors of the various facets of self-concept. Prior to these multiple regressions however, a higher order factor analysis was performed on the body image subscales to identify the underlying dimensions of body image. Five body image factors were revealed: Global Body Esteem, Body Build, Sexual Attractiveness, Physical Condition and Body Emotions body image. These terms were used in the multiple regressions, as were interaction terms developed from the body image factor scores. The research found a complex pattern of development for both body image and self-concept and for the relationship between the two constructs. Overall, it would appear that significant variations in many, but not all, facets of body image and self-concept occur with age and school year level. Furthermore, the majority of these variations appeared to occur between the ages of 13 and 15 and result in less favourable views of self on those dimensions. These more negative evaluations were generally evident throughout the remainder of the adolescent period under consideration. Comparison of the findings for age and school year level revealed a remarkable similarity of results, albeit with a few notable exceptions. Similar to the results for body image and self-concept, the relationship between the two constructs also revealed a complex developmental pattern. Overall it would appear that there is a significant developmental relationship between the dimensions of body image and self-concept, although the particular facets of body image and their constellation across age or school year level varies according to the dimension of self-concept under consideration. All of the facets of body image emerged as important predictors of at least one dimension of self-concept for at least one developmental level, while none was important for all dimensions and all developmental levels. Furthermore, the relationship between the two constructs, body image and self-concept, appeared to be more complex, involving a greater number of dimensions of body image and variance across developmental levels, for some aspects of self-concept than others. In addition, the interactions between the facets of body image were significant predictors for many of the self-concept dimensions. Comparison of the results for age and school year level again revealed a similarity in findings, although less than was evident for the descriptive data. The comments from the interviews with the young women served to both support and extend the quantitative findings. Adolescence was identified by the young women as a critical time in the development of body image, although there appeared to be few developmental changes during adolescence. Rather, it appeared that the adolescents' reactions to the physical changes associated with adolescence resulted in either a temporary or long term decrease in body image. There appeared to be individual characteristics which acted to make the young women more vulnerable to maintaining the lowered body satisfaction common to all female adolescents. These factors included differences in the timing and rate of pubertal change, higher incidence of physical appearance teasing, more frequent comparison with others, stronger subscription to cultural prescriptions regarding female appearance and a social environment, including friends and family, that also expressed concerns with physical appearance. Although overt connections between body image and self-concept in other areas were infrequent, the content of the young women's comments indicated a relationship between the two constructs which varied according to the dimension of functioning under consideration. Findings from both stages of the research have offered insights into the development of body image and self-concept in adolescent females and for the development of the relationship between the two constructs. It would appear that there is an interaction between the individual and their environment, such that both impact on body image and self-concept during adolescence. Suggestions for further research have been highlighted and limitations of the present study identified

Integrated versus non-integrated management and care for clients with co-occurring mental health and substance use disorders: a qualitative systematic review of randomised controlled trials

The purpose of this paper is to conduct a qualitative review of randomised controlled trials in relation to the treatment of adults with co-occurring mental health and substance use disorder (MH/SUD). In particular, integrated approaches are compared with non-integrated approaches to treatment. Ten articles were identified for inclusion in the review. The findings are equivocal with regard to the superior efficacy of integrated approaches to treatment, although the many limitations of the studies need to be considered in our understanding of this finding. Clearly, this is an extremely challenging client group to engage and maintain in intervention research, and the complexity and variability of the problems render control particularly difficult. The lack of available evidence to support the superiority of integration is discussed in relation to these challenges. Much remains to be investigated with regard to integrated management and care for people with co-occurring and MH/SUD, particularly for specific combinations of dual diagnosis and giving consideration to the level of inter-relatedness between the disorders