Mutations of beta-arrestin 2 that limit self-association also interfere with interactions with the beta2-adrenoceptor and the ERK1/2 MAPKs:implications for beta2-adrenoceptor signalling via the ERK1/2 MAPKs

FRET (fluorescence resonance energy transfer) and co-immunoprecipitation studies confirmed the capacity of beta-arrestin 2 to self-associate. Amino acids potentially involved in direct protein-protein interaction were identified via combinations of spot-immobilized peptide arrays and mapping of surface exposure. Among potential key amino acids, Lys(285), Arg(286) and Lys(295) are part of a continuous surface epitope located in the polar core between the N- and C-terminal domains. Introduction of K285A/R286A mutations into beta-arrestin 2-eCFP (where eCFP is enhanced cyan fluorescent protein) and beta-arrestin 2-eYFP (where eYFP is enhanced yellow fluorescent protein) constructs substantially reduced FRET, whereas introduction of a K295A mutation had a more limited effect. Neither of these mutants was able to promote beta2-adrenoceptor-mediated phosphorylation of the ERK1/2 (extracellular-signal-regulated kinase 1/2) MAPKs (mitogen-activated protein kinases). Both beta-arrestin 2 mutants displayed limited capacity to co-immunoprecipitate ERK1/2 and further spot-immobilized peptide arrays indicated each of Lys(285), Arg(286) and particularly Lys(295) to be important for this interaction. Direct interactions between beta-arrestin 2 and the beta2-adrenoceptor were also compromised by both K285A/R286A and K295A mutations of beta-arrestin 2. These were not non-specific effects linked to improper folding of beta-arrestin 2 as limited proteolysis was unable to distinguish the K285A/R286A or K295A mutants from wild-type beta-arrestin 2, and the interaction of beta-arrestin 2 with JNK3 (c-Jun N-terminal kinase 3) was unaffected by the K285A/R286A or L295A mutations. These results suggest that amino acids important for self-association of beta-arrestin 2 also play an important role in the interaction with both the beta2-adrenoceptor and the ERK1/2 MAPKs. Regulation of beta-arrestin 2 self-association may therefore control beta-arrestin 2-mediated beta2-adrenoceptor-ERK1/2 MAPK signalling.

Does self-affirmation promote physical activity regardless of threat level?

Background: Self-affirmation (i.e., focusing on a valued aspect of the self-concept) can promote health behaviour change. This study aimed to see if self-affirmation increased physical activity (PA) regardless of threat level presented in health messages. Methods: Sixty-eight participants were randomly allocated to condition in a 2 (self-affirmation, no affirmation) x 2 (high threat, low threat) between-participants design. Participants completed the Godin Leisure-Time Exercise Questionnaire at baseline and one week later to assess PA. Findings: A two-way ANCOVA with affirmation condition and threat level as predictor variables, controlling for baseline PA, was performed on follow up PA. Baseline PA was a significant predictor (F(1,63) = 399.63, p<0.001) and the main effect of affirmation condition approached significance (F(1,63) = 3.55, p=0.06). There were no other significant effects. Discussion: This study provides further evidence that self-affirmation can increase PA, but found no interaction between self-affirmation and threat level presented in health messages.

Self monitoring of blood glucose in type 2 diabetes:Longitudinal qualitative study of patients' perspectives

Objective: To explore views of patients with type 2 diabetes about self monitoring of blood glucose over time. Design: Longitudinal, qualitative study. Setting: Primary and secondary care settings across Lothian, Scotland. Participants: 18 patients with type 2 diabetes. Main outcome measures: Results from repeat in-depth interviews with patients over four years after clinical diagnosis. Results: Analysis revealed three main themes - the role of health professionals, interpreting readings and managing high values, and the ongoing role of blood glucose self monitoring. Self monitoring decreased over time, and health professionals' behaviour seemed crucial in this: participants interpreted doctors' focus on levels of haemoglobin A1c, and lack of perceived interest in meter readings, as indicating that self monitoring was not worth continuing. Some participants saw readings as a proxy measure of good and bad behaviour - with women especially, chastising themselves when readings were high. Some participants continued to find readings difficult to interpret, with uncertainty about how to respond to high readings. Reassurance and habit were key reasons for continuing. There was little indication that participants were using self monitoring to effect and maintain behaviour change. Conclusions: Clinical uncertainty about the efficacy and role of blood glucose self monitoring in patients with type 2 diabetes is mirrored in patients' own accounts. Patients tended not to act on their self monitoring results, in part because of a lack of education about the appropriate response to readings. Health professionals should be explicit about whether and when such patients should self monitor and how they should interpret and act upon the results, especially high readings.

Blood glucose self-monitoring in non-insulin-treated type 2 diabetes:a qualitative study of patients' perspectives

Background: Self-monitoring of blood glucose is controversial in the management of type 2 diabetes. Some research suggests that self-monitoring improves glycaemic control, whereas other research is sceptical about its value for people with type 2 diabetes who are not on insulin. Although blood glucose meters are widely available and used by this group, patients' own views are absent from the debate. Aim: To explore the pros and cons of glucose monitoring from the patients' perspectives. Design of study: Qualitative repeat-interview study. Setting: Patients were recruited from 16 general practices and three hospital clinics within four local healthcare cooperatives in Lothian, Scotland. Method: Interview data from 40 patients diagnosed with type 2 diabetes within the previous 6 months were analysed using thematic analysis informed by grounded theory. We report findings from round 1 and round 2 interviews. Results: Glucose monitoring can heighten patients' awareness of the impact of lifestyle; for example, dietary choices, on blood glucose levels. Glucose monitoring amplifies a sense of 'success' or 'failure' about self-management, often resulting in anxiety and self-blame if glucose readings remain consistently high. Moreover, monitoring can negatively effect patients' self-management when readings are counter-intuitive. Conclusion: Our analysis highlights the importance of understanding the meanings that newly diagnosed patients attach to glucose self-monitoring. To maximise the positive effects of self-monitoring, health professionals should ensure that patients understand the purpose of monitoring and should clarify with patients how readings should be interpreted. © British Journal of General Practice.

'Urine testing is a waste of time': newly diagnosed Type 2 diabetes patients' perceptions of self-monitoring

Aims To date, there is no convincing evidence that non-insulin treated patients who undertake self-blood glucose monitoring (SBGM) have better glycaemic control than those who test their urine. This has led to a recommendation that non-insulin dependent patients undertake urine testing, which is the cheaper option. This recommendation does not take account of patients' experiences and views. This study explores the respective merits of urine testing and SBGM from the perspectives of newly diagnosed patients with Type 2 diabetes. Methods Qualitative study using repeat in-depth interviews with 40 patients. Patients were interviewed three times at 6-monthly intervals over 1 year. Patients were recruited from hospital clinics and general practices in Lothian, Scotland. The study was informed by grounded theory, which involves concurrent data collection and analysis. Results Patients reported strongly negative views of urine testing, particularly when they compared it with SBGM. Patients perceived urine testing as less convenient, less hygienic and less accurate than SBGM. Most patients assumed that blood glucose meters were given to those with a more advanced or serious form of diabetes. This could have implications for how they thought about their own disease. Patients often interpreted negative urine results as indicating that they could not have diabetes. Conclusions Professionals should be aware of the meanings and understandings patients attach to the receipt and use of different types of self-monitoring equipment. Guidelines that promote the use of consistent criteria for equipment allocation are required. The manner in which negative urine results are conveyed needs to be reconsidered.

Education and self-management for people newly diagnosed with type 2 diabetes: a qualitative study of patients' views.

OObjectives: We explored the perceptions, views and experiences of diabetes education in people with type 2 diabetes who were participating in a UK randomized controlled trial of methods of education. The intervention arm of the trial was based on DESMOND, a structured programme of group education sessions aimed at enabling self-management of diabetes, while the standard arm was usual care from general practices. Methods: Individual semi-structured interviews were conducted with 36 adult patients, of whom 19 had attended DESMOND education sessions and 17 had been randomized to receive usual care. Data analysis was based on the constant comparative method. Results: Four principal orientations towards diabetes and its management were identified: `resisters', `identity resisters, consequence accepters', `identity accepters, consequence resisters' and `accepters'. Participants offered varying accounts of the degree of personal responsibility that needed to be assumed in response to the diagnosis. Preferences for different styles of education were also expressed, with many reporting that they enjoyed and benefited from group education, although some reported ambivalence or disappointment with their experiences of education. It was difficult to identify striking thematic differences between accounts of people on different arms of the trial, although there was some very tentative evidence that those who attended DESMOND were more accepting of a changed identity and its implications for their management of diabetes. Discussion: No one single approach to education is likely to suit all people newly diagnosed with diabetes, although structured group education may suit many. This paper identifies varying orientations and preferences of people with diabetes towards forms of both education and self-management, which should be taken into account when planning approaches to education.

Reversible addition–fragmentation chain transfer polymerization of 2-chloro-1,3-butadiene

Controlled polymerization of 2-chloro-1,3-butadiene using reversible addition–fragmentation chain transfer (RAFT) polymerization has been demonstrated for the first time. 2-Chloro-1,3-butadiene, more commonly known as chloroprene, has significant industrial relevance as a crosslinked rubber, with uses ranging from adhesives to integral automotive components. However, problems surrounding the inherent toxicity of the lifecycle of the thiourea-vulcanized rubber have led to the need for control over the synthesis of poly(2-chloro-1,3-butadiene). To this end, four chain transfer agents in two different solvents have been trialed and the kinetics are discussed. 2-Cyano-2-propylbenzodithioate (CPD) is shown to polymerize 2-chloro-1,3-butadiene in THF, using AIBN as an initiator, with complete control over the target molecular weight, producing polymers with low polydispersities (Mw/Mn < 1.25 in all cases).

Self-monitoring of blood glucose in Black Caribbean and South Asian Canadians with non-insulin treated Type 2 diabetes mellitus:a qualitative study of patients' perspectives

Background: To examine the views and current practice of SMBG among Black Caribbean and South Asian individuals with non-insulin treated Type 2 diabetes mellitus. Methods: Twelve participants completed semi-structured interviews that were guided by the Health Belief Model and analyzed using thematic network analysis. Results: The frequency of monitoring among participants varied from several times a day to once per week. Most participants expressed similar experiences regarding their views and practices of SMBG. Minor differences across gender and culture were observed. All participants understood the benefits, but not all viewed SMBG as beneficial to their personal diabetes management. SMBG can facilitate a better understanding and maintenance of self-care behaviours. However, it can trigger both positive and negative emotional responses, such as a sense of disappointment when high readings are not anticipated, resulting in emotional distress. Health care professionals play a key role in the way SMBG is perceived and used by patients. Conclusion: While the majority of participants value SMBG as a self-management tool, barriers exist that impede its practice, particularly its cost. How individuals cope with these barriers is integral to understanding why some patients adopt SMBG more than others. © 2013 Gucciardi et al.; licensee BioMed Central Ltd.