Analysis of CXCR6-mediated signal transduction in T-lymphocytes

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A dual role for microglia in promoting tissue inhibitor of metalloproteinase (TIMP) expression in glial cells in response to neuroinflammatory stimuli

<p>Abstract</p> <p>Background</p> <p>By neutralizing the effect of the matrix metalloproteinases (MMPs), the tissue inhibitors of matrix metalloproteinases (TIMPs) play a critical role in maintaining tissue proteolysis in balance. As the major reactive glial cell types in the central nervous system (CNS), microglia and astrocytes play fundamental roles in mediating tissue breakdown and repair. As such, it is important to define the TIMP expression profile in these cells, as well as the mechanisms of regulation by neuroinflammatory stimuli.</p> <p>Methods</p> <p>Primary mixed glial cultures (MGC), pure microglia, and pure astrocytes were used in this study. To study astrocytes, we employed a recently described pure astrocyte culture system, which has the major advantage of totally lacking microglia. The three different types of culture were treated with lipopolysaccharide (LPS) or individual cytokines, and cell culture supernatants assayed for TIMP-1 or TIMP-2 protein expression by western blot.</p> <p>Results</p> <p>LPS induced TIMP-1 expression in MGC, but not in pure astrocyte or microglial cultures. When pure astrocytes were treated with the cytokines IL-1β, IFN-γ, TNF or TGF-β1, only IL-1β induced TIMP-1 expression. Significantly, astrocyte TIMP-1 expression was restored in LPS-treated astrocyte cultures after the addition of microglia, or conditioned medium taken from LPS-activated microglia (MG-CM). Furthermore, this effect was lost after depletion of IL-1β from MG-CM. By contrast, TIMP-2 was constitutively expressed by astrocytes, whereas microglia expressed TIMP-2 only after exposure to serum.</p> <p>Conclusions</p> <p>Taken together, these results demonstrate an important concept in glial interactions, by showing that microglia play a central role in regulating glial cell expression of TIMPs, and identify microglial IL-1β as playing a key role in mediating microglial-astrocyte communication.</p

Acquiring Knowledge and Learning from Failure : Theory, Measurement, and Validation of Two Learning Goals

We report the development and validation of a measure that distinguished knowledge goals focused on acquiring knowledge and information from learning from failure goals focused on using failure as an opportunity to learn. In Study 1, the scale demonstrated a robust factor structure and adequate internal consistencies, and the two learning goals differently correlated with measures of ego-involved achievement goals. In Study 2, the goal to learn from failure interacted with academically contingent selfworth, reducing self-esteem vulnerability when people invested effort and failed. In Study 3, the goal to learn from failure reduced the effect of academic contingencies of self-worth on self-esteem, especially among the incremental theorists who invested effort prior to failure

Interdependent = Compassionate? Compassionate and Self-Image Goals and Their Relationships With Interdependence in the United States and Japan

The pursuit of compassionate goals, which involves focusing on and attending to other people’s needs, has often been described as a defining characteristic of an interdependent self that prioritizes harmonious relationships over individual achievement. This research investigated whether compassionate goals can be empirically distinguished from various indices of interdependence and examined their correlations with interdependence in both American and Japanese adult samples. It further differentiated two types of self-image goals—the goals to appear warm and kind vs. the goals to appear competent and in control—and explored their relationships with interdependence. In Study 1, the 18-item scale showed a clear four-factor structure that distinguished (a) compassionate goals, (b) approach-worded likable self-image goals, (c) approach-worded competent self-image goals, and (d) avoidance-worded self-image goals. Study 2 confirmed the equivalence of the four-factor structure and the equivalence of factor loadings in the United States and Japan. Finally, Study 3 showed that the items of compassionate goals and those of various measures of interdependence loaded onto separate factors with only negligible cross-loadings. Study 3 further found that the indices of interdependence reflecting connection with others showed moderately positive correlations with compassionate goals whereas indices of interdependence reflecting conformity showed moderate correlations with likable, competent, and avoidant self-image goals, indicating that the pursuit of compassionate and self-image goals reflect different aspects of interdependence

Imagining Success for a Restorative Approach to Justice: Implications for Measurement and Evaluation

Whether restorative justiceis successful, or not, is a complex question. Attempts to answer this question by practitioners, professionals, and scholars have often been bounded by common notions of success in standard criminal justice terms. The authors of this paper suggest that ifrestorative justice is properly understood in terms of its focus on relationship, success should be measured on new and different dimensions. This paper seeks to bring a relational imagination to the scholarly effort of capturing the essence ofrestorative justice and figuring out how to assess its successes and failures. The authors offer a foundation and agenda for future research and development of a relational approach to assessment

Impact of patient and public involvement on enrolment and retention in clinical trials: Systematic review and meta-analysis

© Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to. Objective To investigate the impact of patient and public involvement (PPI) on rates of enrolment and retention in clinical trials and explore how this varies with the context and nature of PPI. Design Systematic review and meta-analysis. Data sources Ten electronic databases, including Medline, INVOLVE Evidence Library, and clinical trial registries. Eligibility criteria Experimental and observational studies quantitatively evaluating the impact of a PPI intervention, compared with no intervention or non-PPI intervention(s), on participant enrolment and/or retention rates in a clinical trial or trials. PPI interventions could include additional non-PPI components inseparable from the PPI (for example, other stakeholder involvement). Data extraction and analysis Two independent reviewers extracted data on enrolment and retention rates, as well as on the context and characteristics of PPI intervention, and assessed risk of bias. Random effects meta-analyses were used to determine the average effect of PPI interventions on enrolment and retention in clinical trials: main analysis including randomised studies only, secondary analysis adding non-randomised studies, and several exploratory subgroup and sensitivity analyses. Results 26 studies were included in the review; 19 were eligible for enrolment meta-analysis and five for retention meta-analysis. Various PPI interventions were identified with different degrees of involvement, different numbers and types of people involved, and input at different stages of the trial process. On average, PPI interventions modestly but significantly increased the odds of participant enrolment in the main analysis (odds ratio 1.16, 95% confidence interval and prediction interval 1.01 to 1.34). Non-PPI components of interventions may have contributed to this effect. In exploratory subgroup analyses, the involvement of people with lived experience of the condition under study was significantly associated with improved enrolment (odds ratio 3.14 v 1.07; P=0.02). The findings for retention were inconclusive owing to the paucity of eligible studies (odds ratio 1.16, 95% confidence interval 0.33 to 4.14), for main analysis). Conclusions These findings add weight to the case for PPI in clinical trials by indicating that it is likely to improve enrolment of participants, especially if it includes people with lived experience of the health condition under study. Further research is needed to assess which types of PPI work best in particular contexts, the cost effectiveness of PPI, the impact of PPI at earlier stages of trial design, and the impact of PPI interventions specifically targeting retention. Systematic review registration PROSPERO CRD42016043808

Illness Labels and Social Distance

The authors examine a key proposition in the modified labeling theory—that a psychiatric label increases vulnerability to negative evaluation and social rejection—using an experimental design wherein female participants interact with a female teammate over a computer. The authors also evaluate a hypothesis derived from the disease-avoidance account of disgust by examining this same process for a nonpsychiatric illness: food poisoning. In addition, they introduce a composite measure of social distance behavior that is easy to implement in a laboratory experiment. The authors find, as predicted, that women seek greater social distance from teammates with a history of psychiatric or food poisoning hospitalization than they do from teammates with no hospitalization history. But, contrary to predictions, a teammate’s hospitalization history does not affect participants’ ratings of her likability. The results also do not vary significantly by psychiatric diagnosis (depression vs. schizophrenia), suggesting that the stigma of depression may be just as strong as the stigma of schizophrenia when information about symptoms is not available. The authors discuss the implications of these findings for the modified labeling theory of mental illness and for the literature on disgust and stigma. They also outline avenues for future research.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Patient and public involvement (PPI) in UK surgical trials: a survey and focus groups with stakeholders to identify practices, views, and experiences

Background and aims Historically, patient and public involvement (PPI) in the design and conduct of surgical trials has been absent or minimal, but it is now routinely recommended and even required by some research funders. We aimed to identify and describe current PPI practice in surgical trials in the United Kingdom, and to explore the views and experiences of surgical trial staff and patient or public contributors in relation to these practices. This was part of a larger study to inform development of a robust PPI intervention aimed at improving recruitment and retention in surgical trials. Methods Our study had two stages: 1) an online survey to identify current PPI practice in active UK-led, adult surgical trials; and 2) focus groups and interviews with key stakeholders (surgical trial investigators, administrators, and patient or public contributors) to explore their views and experiences of PPI. Results Of 129 eligible surgical trial teams identified, 71 (55%) took part in the survey. In addition, 54 stakeholders subsequently took part in focus groups or interviews. Sixty-five (92%) survey respondents reported some kind of PPI, most commonly at the design and dissemination stages and in oversight or advisory roles. The single most common PPI activity was developing participant information sheets (72%). Participants reported mixed practice and views on a variety of issues including the involvement of patients versus lay members of the public, recruitment methods, use of role descriptions and payment for the time of PPI contributors. They suggested some solutions, including the use of written role descriptions and databases of potential PPI contributors to aid recruitment. Conclusions UK surgical trials involve patients and members of the public in a variety of different ways, most commonly at the beginning and end of the trial lifecycle and in oversight or advisory roles. These are not without challenges and there remain uncertainties about who best to involve, why, and how. Future research should aim to address these issues