Behaviour change in diabetes: behavioural science advancements to support the use of theory.

Behaviour is central to the management of diabetes, both for people living with diabetes and for healthcare professionals delivering evidence-based care. This review outlines the evolution of behavioural science and the application of theoretical models in diabetes care over the past 25 years. There has been a particular advancement in the development of tools and techniques to support researchers, healthcare professionals and policymakers in taking a theory-based approach, and to enhance the development, reporting and replication of successful interventions. Systematic guidance, theoretical frameworks and lists of behavioural techniques provide the tools to specify target behaviours, identify why ideal behaviours are not implemented, systematically develop theory-based interventions, describe intervention content using shared terminology, and evaluate their effects. Several examples from a range of diabetes-related behaviours (clinic attendance, self-monitoring of blood glucose, retinal screening, setting collaborative goals in diabetes) and populations (people with type 1 and type 2 diabetes, healthcare professionals) illustrate the potential for these approaches to be widely translated into diabetes care. The behavioural science approaches outlined in this review give healthcare professionals, researchers and policymakers the tools to deliver care and design interventions with an evidence-based understanding of behaviour. The challenge for the next 25 years is to refine the tools to increase their use and advocate for the role of theoretical models and behavioural science in the commissioning, funding and delivery of diabetes care.

'It's an important part, but I am not quite sure that it is working': educators' perspectives on the implementation of goal-setting within the 'DAFNE' diabetes structured education programme.

AIM: To explore educators' perspectives on the implementation of goal-setting and action-planning strategies within a structured diabetes self-management education programme. METHODS: Ten semi-structured interviews were conducted with diabetes self-management education providers delivering the 'Dose Adjustment for Normal Eating' (DAFNE) programme to people with Type 1 diabetes throughout Ireland. A pre-designed topic guide, focused on exploring educators' experiences of delivery and application and views on usefulness of goal-setting strategies, was used in all interviews. The interviews were recorded, transcribed and analysed using thematic analysis. RESULTS: Five main themes were identified: 'people need a plan', discussing perspectives on goal-setting's value; 'the power of the group', highlighting the impact a group format has on goal-setting practices; 'diversity and individuality', discussing differences in DAFNE participants' and educators' engagement with goal-setting; 'goal-setting's fit', exploring perspectives on how well goal-setting fits within diabetes self-management education and follow-up care; and 'feelings of inadequate psychological knowledge', addressing challenges experienced in the delivery of goal-setting components. CONCLUSION: While educators saw benefits in the implementation of goal-setting and planning strategies within diabetes self-management education, concerns about how well goal-setting currently fits within diabetes self-management education and follow-up care were evident. Additionally, many educators experienced the delivery of goal-setting and action-planning strategies as challenging and would value additional training opportunities.

Perceptions and experiences of taking oral medications for the treatment of Type 2 diabetes mellitus: a systematic review and meta-synthesis of qualitative studies.

AIMS: To explore patients' perceptions and experiences of taking oral medications for the pharmacological management of Type 2 diabetes mellitus. METHODS: Cinahl, EMBASE, Medline and PsycINFO databases were searched in 2014 to identify qualitative studies exploring patients' perceptions or experiences of taking medications for the management of Type 2 diabetes. Key concepts and themes were extracted and synthesized using meta-ethnography. RESULTS: Eight studies were included. Primary study findings were synthesized to develop three higher-order constructs that moved beyond the results of individual studies. The first construct, Medications for diabetes: a necessary evil, outlines how patients' negative perceptions of medication risks co-exist with a resounding view that medications are beneficial. Passive patients but active experimenters highlights the contrast between patients' passive acceptance of medication prescriptions and the urge to actively experiment and adjust doses to optimize medication use in daily life. Finally, Taking oral medication for Type 2 diabetes: a unique context describes features specific to the Type 2 diabetes medication experience, including lack of symptoms and the perceived relationship between medication and diet, which may influence adherence. CONCLUSIONS: Medication-taking for Type 2 diabetes is a unique adherence context, which requires the development of condition-specific interventions. The present findings indicate patients understand the need for medications but adjust dosage and timing in their daily lives. This review suggests providers should acknowledge patient preferences in the development of management strategies, and highlights an opportunity to direct the motivation evident in patients' experimentation towards potentially more beneficial medication-taking behaviours.

Effects of interventions promoting monitoring of medication use and brief messaging on medication adherence for people with Type 2 diabetes: a systematic review of randomized trials.

AIMS: To assess the impact of interventions promoting the monitoring of medication use and brief messaging to support medication adherence in patients with Type 2 diabetes mellitus, and to investigate the extent of theory use to guide intervention development. METHODS: We systematically searched for controlled trials, published from 1990 onwards in Medline, Embase, CINAHL, PsycINFO and the Cochrane library, that evaluated interventions based on monitoring and brief messaging to support medication adherence in patients with Type 2 diabetes, to examine the effectiveness of such interventions. RESULTS: A total of 11 trials, comparing 15 interventions, were identified. Only a small minority presented a low risk of bias. Three interventions were based on delivering brief messages, six were based on monitoring medication adherence, and six used both strategies. Messaging interventions included the use of short message service text messages, web-based feedback, and messages delivered through monitoring devices. Monitoring interventions included remote self-reporting of medication and telephone calls with healthcare staff. Improvements in medication adherence were observed in six interventions, although effect sizes were generally moderate. Only two interventions improved both adherence and clinical outcomes. A meta-analysis of five trials (eight interventions) combining monitoring and messaging strategies showed that the pooled difference in medication adherence between intervention and control was moderate and not statistically significant [standardized mean difference = 0.22 (95% CI -0.05; 0.49)]. Only four trials were based on explicit theoretical frameworks. CONCLUSIONS: Although interventions based on messaging and monitoring have the potential to improve medication adherence in patients with Type 2 diabetes, evidence of their efficacy is limited and additional high-quality, theory-based research is needed.

The glycoprotein isolated from vesicular stomatitis virus is mitogenic for mouse B lymphocytes.

The glycoprotein (G protein) of VSV was purified from the intact virion by Triton X-100 extraction. The isolated G protein has been shown to be a T cell-independent, B lymphocyte mitogen and polyclonal activator. Neither G protein nor the intact virion are stimulatory for murine T lymphocytes. The greater the density of G protein in lipid vesicles or the degree of aggregation of isolated G protein, the more highly stimulatory it is for murine splenocytes. As G protein is spread out in artificial vesicles, it becomes less mitogenic. It is probable that other viral components are also stimulatory since the Triton-insoluble pellet and VSV from which the G protein has been enzymatically removed retain mitogenic activity. To out knowledge, this is the first time a purified viral component has been demonstrated to be lymphocyte mitogen.

Focusing on fidelity: narrative review and recommendations for improving intervention fidelity within trials of health behaviour change interventions.

Background: Interventions to change behaviour have substantial potential to impact positively on individual and overall public health. Despite an increasing focus on health behaviour change intervention research, interventions do not always have the desired effect on outcomes, while others have diluted effects once implemented into real-life settings. There is little investment into understanding how or why such interventions work or do not work. Methodological inadequacies of trials of behavioural interventions have been previously suggested as a barrier to the quality and advancement of behavioural research, with intervention fidelity acknowledged as a key area for improvement. However, there is much ambiguity regarding the terminology and conceptualisation of intervention fidelity and a lack of practical guidance regarding how to address it sufficiently, particularly within trials of complex behavioural interventions. Objectives: This article outlines specific issues concerning intervention fidelity within trials of health behaviour change interventions and suggests practical considerations and specific recommendations for researchers, with examples from the literature presented. Conclusions: Recommendations pertain to (1) clarifying how fidelity is defined and conceptualised, (2) considering fidelity beyond intervention delivery, (3) considering strategies to both enhance and assess fidelity, (4) making use of existing frameworks and guidance, (5) considering the quality and comprehensiveness of fidelity assessment strategies, (6) considering the balance between fidelity and adaptation and (7) reporting the use of fidelity enhancement and assessment strategies and their results. Suggestions for future research to improve our understanding of, and ability to, address fidelity in behaviour change interventions are also provided.

Parental experiences and perceptions of infant complementary feeding: a qualitative evidence synthesis.

BACKGROUND: Interventions to prevent childhood obesity increasingly focus on infant feeding, but demonstrate inconsistent effects. A comprehensive qualitative evidence synthesis is essential to better understand feeding behaviours and inform intervention development. The aim of this study is to synthesize evidence on perceptions and experiences of infant feeding and complementary feeding recommendations. METHODS: Databases CINAHL, EMBASE, MEDLINE, PsycINFO, Academic Search Complete, SocIndex and Maternity and Infant Care were searched from inception to May 2017. Eligible studies examined parents' experiences of complementary feeding of children (<2 years). Data were synthesized using thematic synthesis. RESULTS: Twenty-five studies met inclusion criteria for review. Four key themes emerged. 'Guidelines and advice' highlights variety and inconsistencies between sources of complementary feeding information. 'Stage of weaning' describes infant feeding as a process involving different stages. 'Knowing and trying' outlines parents' engagement in feeding approaches based on instinct, prior experience or trial and error. 'Daily life' highlights problematic cost and time constraints for parents. DISCUSSION: Parents predominantly understand and want to engage in healthy feeding processes. Consideration of infant feeding as a process that changes over time is necessary to support parents. Provision of clear, consistent information and guidance from trusted sources on when, what and how to feed is also essential.

Novel oral combination chemotherapy in the treatment of intermediate-grade and high-grade AIDS-related non-Hodgkin's lymphoma.

PURPOSE: To determine the toxicity, response, and survival rate of orally administered combination chemotherapy in patients with AIDS-related intermediate- and high-grade non-Hodgkin's lymphoma. Secondary objectives included prospective quality-of-life assessment and quantitation of cell-associated p24 antigen (p24 Ag) by flow cytometry. PATIENTS AND METHODS: Eighteen patients with biopsy-proven lymphoma were treated with oral chemotherapy consisting of lomustine (CCNU) 100 mg/m2 on day 1, etoposide 200 mg/m2 on days 1 through 3; cyclophosphamide 100 mg/m2 on days 22 through 31, and procarbazine 100 mg/m2 on days 22 through 31 at 6-week intervals. A variety of clinical assessments were performed: prospective quality-of-life assessment using the Functional Living Index-Cancer (FLIC) and Brief Symptom Inventory (BSI) instruments; indirect immunofluorescence with flow cytometry to measure cell-associated p24 antigen; and price of the oral regimen compared with two other intravenous combination chemotherapy regimens. RESULTS: The overall objective response rate using Eastern Cooperative Oncology Group (ECOG) criteria was 61% (95% confidence interval, 39% to 84%), with seven complete remissions (39%) and four partial remissions (22%). The median survival duration was 7 months, with a range of 11 days to 36 months. The treatment-related mortality rate was 11%. One patient developed CNS progression. Myelosuppression was the most frequent and severe toxicity encountered. Predictor variables of performance status (PS), prior history of thrush, and CD4 lymphocyte count were found to be of prognostic value. In a separate analysis, scores on the three subscales of the BSI were also found to be predictive of complete response. The price of this regimen is several thousand dollars less than that of other intravenous combination chemotherapy regimens. CONCLUSION: This regimen is active in patients with AIDS-related non-Hodgkin's lymphoma. Because it is important to design systemic cytotoxic chemotherapy regimens that are cost-effective, considerate of quality-of-life issues, and efficacious in this patient population, this approach should be compared with standard intravenous combination chemotherapy regimens in randomized controlled clinical trials.

Antiviral drug susceptibility assays: going with the flow.

This review describes the procedures for the use of fluorochrome labeled monoclonal antibodies and flow cytometry for the detection and quantification of virus infected cells. The application of this technology for (1) identifying virus infected cells in clinical specimens obtained from human cytomegalovirus (HCMV) and human immunodeficiency virus (HIV) infected individuals; (2) screening antiviral compounds active against HCMV, HDSV and HIV; and (3) performing drug susceptibility testing for HCMV, HSV and HIV clinical isolates are reviewed. The flow cytometry drug susceptibility assay is rapid, quantitative, and easily performed. It should be considered by anyone interested in performing drug susceptibility testing for any virus for which there are reliable monoclonal antibodies.

Association of cocaine use with sperm concentration, motility, and morphology.

Use of cocaine within 2 years of their first semen analysis has been found to be twice as common among men with sperm counts less than 20 X 10(6) mL (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.0, 4.6). Duration of cocaine use for five or more years was more common in men with low sperm motility (OR = 2.0, 95% CI 1.0, 4.1) and in those with low concentrations and a large proportion of abnormal forms. Other major risk factors for these three indicators of male subfertility also have been identified, but the cocaine risk factors remained after adjustment for them. This association, together with the high prevalence of cocaine use in the general male population, suggests cocaine may now be related to male subfertility and that history of use should be ascertained during diagnostic interviews.

Dietary titanium and infant growth.

Dietary titanium as TiO2+ improved animal growth during infancy while inhibiting the metabolism of intestinal bacteria. TiO2+ was also found capable of inhibiting human cytomegalovirus in tissue culture. These and other findings indicate TiO2+ improves infant growth by acting as an antibacterial and antiviral agent. The behavior of TiO2+ stands in contrast to that of TiO2, which is inert.

Analysis of virus-infected cells by flow cytometry.

Flow cytometry has been used to study virus-cell interactions for many years. This article critically reviews a number of reports on the use of flow cytometry for the detection of virus-infected cells directly in clinical samples and in virus-infected cultured cells. Examples are presented of the use of flow cytometry to screen antiviral drugs against human immunodeficiency virus (HIV), human cytomegalovirus, and herpes simplex viruses (HSV) and to perform drug susceptibility testing for these viruses. The use of reporter genes such as green fluorescent protein incorporated into HIV or HSV or into cells for the detection of the presence of virus, for drug susceptibility assay, and for viral pathogenesis is also covered. Finally, studies on the use of flow cytometry for studying the effect of virus infection on apoptosis and the cell cycle are summarized. It is hoped that this article will give the reader some understanding of the great potential of this technology for studying virus cell interactions.

Uses of flow cytometry in virology.

This article reviews some of the published applications of flow cytometry for in vitro and in vivo detection and enumeration of virus-infected cells. Sample preparation, fixation, and permeabilization techniques for a number of virus-cell systems are evaluated. The use of flow cytometry for multiparameter analysis of virus-cell interactions for simian virus 40, herpes simplex viruses, human cytomegalovirus, and human immunodeficiency virus and its use for determining the effect of antiviral compounds on these virus-infected cells are reviewed. This is followed by a brief description of the use of flow cytometry for the analysis of several virus-infected cell systems, including blue tongue virus, hepatitis C virus, avian reticuloendotheliosis virus, African swine fever virus, woodchuck hepatitis virus, bovine viral diarrhea virus, feline leukemia virus, Epstein-Barr virus, Autographa californica nuclear polyhedrosis virus, and Friend murine leukemia virus. Finally, the use of flow cytometry for the rapid diagnosis of human cytomegalovirus and human immunodeficiency virus in peripheral blood cells of acutely infected patients and the use of this technology to monitor patients on antiviral therapy are reviewed. Future prospects for the rapid diagnosis of in vivo viral and bacterial infections by flow cytometry are discussed.

Agrobacterium tumefaciens Conn. IV. Bacteriophage PB21 and its inhibitory effect on tumor induction.

Strain B2 of Agrobacterium tumefaciens Conn produces plaques when seeded against strain B6-806 of the same organism. From such a plaque, a highly virulent bacteriophage was obtained by use of D'Herelle's technique of selecting for virulent phage. On nutrient agar, this phage, PB2(1), produced large clear plaques which did not overgrow. Plaques produced on a glutamate medium and on White's plant tissue culture medium were even larger and in White's medium had a three-dimensional appearance. PB2(1) does not appear to be an oncogenic virus. To the contrary, the addition of phage under circumstances which insure mass lysis completely inhibited tumor initiation. Fewer than 10 phage particles present at the beginning of a 21-hr induction period were able, at times, to inhibit completely tumor induction by highly virulent bacteria (strain B6). The data lend further support to the concept that anything which interferes with the metabolic activity associated with the growth of the bacteria interferes with the tumor-inducing process. Attempts to use the phage to rid crown gall tissue of bacteria were unsuccessful.

Mitogenic activity of Sindbis virus and its isolated glycoproteins.

Purified preparations of Sindbis virus, a member of the togavirus family, are mitogenic for lymphocytes from a number of different mouse strains. Cell separation techniques, as well as studies using lymphocytes from the congenitally athymic BALB/c nu/nu mouse, showed that Sindbis virus is a T-cell-independent B-cell mitogen. Additionally, the envelope glycoproteins of Sindbis virus, isolated by Triton X-100 extraction and butanol precipitation, stimulated lymphocytes to incorporate five times as much [3H]thymidine into their DNA as did the Sindbis virion. These results are similar to those previously reported for vesicular stomatitis virus and herpes simplex virus types I and II and for the purified glycoproteins of vesicular stomatitis virus and influenza virus.

Carbohydrate composition of vesicular stomatitis virus.

Analysis by gas-liquid chromatography of the trimethylsilylated sugar residues of purified vesicular stomatitis virus grown in L cells or chick embryo cells revealed the presence in the whole virion of four hexoses (glucose, galactose, mannose, and fucose), two hexosamines (glucosamine and galactosamine), and 34 to 40% neuraminic acid. The isolated viral glycoprotein was devoid of galactosamine and fucose, both of which sugars were present in whole virions presumably as part of the membrane glycolipids.

Lipid composition of purified vesicular stomatitis viruses.

Methods are described for the production of vesicular stomatitis (VS) virus of sufficient purity for reliable chemical analysis. VS virions released from infected cells were concentrated and purified at least 150-fold by sequential steps of precipitation with polyethylene glycol, column chromatography, rate zonal centrifugation, and equilibrium centrifugation. The Indiana serotype (VS(Ind) virus) propagated in L-cells was found to contain 3% ribonucleic acid, 64% protein, 13% carbohydrate, and 20% lipid; the molar ratio of cholesterol to phospholipid was 0.6 or greater. Thin-layer chromatography revealed no unusual neutral lipids or phospholipids and gas-liquid chromatography revealed no unusual fatty acids incorporated into VS virions. The antigenically distinct New Jersey serotype (VS(NJ) virus) grown in L-cells showed a similar lipid profile except that the proportion of neutral lipids was larger than in VS(Ind) virus also grown in L-cells. This differences was less pronounced when the lipid composition of VS(Ind) and VS(NJ) viruses grown in chick embryo cells was compared, but VS(NJ) virus grown in either cell type always contained larger amounts of neutral lipids other than cholesterol than did VS(Ind) virus. The lipid composition of both VS(Ind) and VS(NJ) viruses grown in L-cells or chick embryo cells more closely resembled that of plasma membrane than of whole cells. A consistent finding was the relatively large amounts of phosphatidylethanolamine and sphingomyelin and the relatively small amounts of phosphatidylcholine in both VS viruses compared with uninfected whole L-cells and chick embryo cells or their plasma membranes. The methods available for isolation of plasma membranes were inadequate for conclusive comparison of the lipids of VS virions with the lipids of the plasma membranes of their host cells. Nevertheless, the data obtained are consistent with two hypotheses: (i) the lipid composition of VS viruses primarily reflects their membrane site of maturation, and (ii) the newly synthesized viral proteins inserted into cell membranes influence the proportions of phospholipids and neutral lipids selected for incorporation into the viral membrane.

Activation of mouse lymphocytes by vesicular stomatitis virus.

Vesicular stomatitis virus (VSV) is a mitogen for mouse spleen cells, and infectious virus is not required for mitogenesis. At concentrations between 10 and 100 microgram per culture, VSV stimulated DNA synthesis and blast transformation. Maximal activation by VSV occurred 48 h after culture initiation. Spleen cells depleted of T-lymphocytes by treatment with anti-Thy 1.2 and complement and those obtained from congenitally athymic BALB/c nu/nu mice were activated by VSV, suggesting that VSV is a B-cell mitogen. Activation of spleen cells was independent of the host in which the virus was grown, since VSV grown in BHK-21, HKCC, or MDBK cells was mitogenic. The mitogenesis was specific for VSV, since MDBK cell-grown WSN influenza virus was not a mitogen in this in vitro activation system, VSV-specific antibody prevented VSV mitogenesis, and VSV was mitogenic for spleen cells from C3H/HeJ mice which were resistant to mitogenesis by endotoxin.

Agrobacterium tumefaciens Conn. 3. Effect of thermal shock on bacteria in relation to tumorinducing ability.

Stonier, Tom (Manhattan College, Bronx, N.Y.), Robert E. Beardsley, Lowell Parsons, and James McSharry. Agrobacterium tumefaciens Conn. III. Effect of thermal shock on bacteria in relation to tumor-inducing ability. J. Bacteriol. 91:266-269. 1966.-Bacteria heated to 42 C for 30 min exhibit a decrease in tumor-initiating ability without a detectable loss in viability. The thermal shock inhibits subsequent bacterial growth for up to 1.5 hr. As bacterial growth recovers, so does tumor-initiating ability. Respiration of the culture is somewhat increased by the heat treatment. The data suggest that living, actively respiring bacteria do not induce tumors unless they are also growing. The results also point to the necessity for excluding bacterial growth inhibition when interpreting data on the effect of various agents on tumor initiation.