Videogames That Encourage Healthy Behavior Did Not Alter Fasting Insulin or Other Diabetes Risks in Children: Randomized Clinical Trial.

Background: Previous research indicates games for health have substantial promise in promoting change in children's diet and physical activity (PA) behavior for obesity and diabetes prevention, but the research has generally not been rigorous. The study reported here was an efficacy trial of two role-playing videogames played in sequence, "Escape from Diab" (hereinafter called Diab) and "Nanoswarm: Invasion from Inner Space" (hereinafter called Nano), on diabetes and obesity risk factors: fasting insulin and body mass index (BMI), and risk-related behaviors: diet, PA, and sedentary behavior (SB). Design: A two-group (treatment vs. wait list control) randomized clinical trial was used with baseline, immediate postintervention (∼3 months postbaseline), and 2 months postassessments. Intervention: Diab and Nano were desktop or laptop role-playing videogames with nine sessions (each episode/session lasting ∼60 minutes). Two storylines attempted to immerse players and used ethnically diverse characters to model desired behaviors. Tailored goal setting, problem solving, and motivational statements were used. Methods: A sample of 200 overweight or obese children (ages 10-12 years from 85th to 99th BMI percentile [%ile]) was recruited, primarily using a volunteer list. Fasting insulin was the primary dependent variable. BMI, fruit, vegetable and sweetened beverage intakes, PA, and SBs were secondary outcomes. Generalized linear mixed models were used to test for the treatment effects. Results: No significant differences were detected in any of the tested outcome variables. Conclusions: The lack of differences may indicate that games cannot change dietary behaviors and thereby not change-related clinical outcomes. Alternatively, there seem to have been changes in (1) the types of videogames children expect and like to play since a pilot study was conducted, (2) productization challenges, and/or (3) problems in staff management of the trial. All may have contributed to the lack of effect.

A rare population of tumor antigen-specific CD4+CD8+ double-positive αß T lymphocytes uniquely provide CD8-independent TCR genes for engineering therapeutic T cells.

BACKGROUND: High-affinity tumor antigen-specific T-cell receptor (TCR) gene is required to engineer potent T cells for therapeutic treatment of cancer patients. However, discovery of suitable therapeutic TCR genes is hampered by the fact that naturally occurring tumor antigen-specific TCRs are generally of low-affinity, and artificial modification of TCRs can mediate cross-reactivity to other antigens expressed in normal tissues. Here, we discovered a naturally occurring T-cell clone which expressed high-affinity HLA-A*02:01 (A*02)-restricted TCR against NY-ESO-1 from a patient who had NY-ESO-1-expressing ovarian tumor. METHODS: A*02-restricted NY-ESO-1-specific T-cell clones were established from peripheral blood of patients who had NY-ESO-1-expressing ovarian tumors. TCR α and ß chain genes were retrovirally transduced into polyclonally activated T cells. Phenotype and function of the parental and TCR-transduced T cells were analyzed by flow cytometry, ELISA and cytotoxicity assay. In vivo therapeutic efficacy was investigated in a xenograft model using NOD/SCID/IL-2Rγ-deficient (NSG) mice. RESULTS: A rare population of NY-ESO-1-specific T cells, which we named 19305DP, expressed cell surface CD4, CD8α, and CD8ß but not CD56 and recognized A*02+NY-ESO-1+ cancer cell lines in a CD4- and CD8-independent manner. 19305DP showed a gene expression profile that is consistent with a mixed profile of CD4+ and CD8+ single-positive T cells. Both CD4+ and CD8+ T cells that were retrovirally transduced with 19305DP-derived TCR gene (19305DP-TCR) showed strong reactivity against A*02+NY-ESO-1+ cancer cells, whereas TCR genes from the conventional A*02-restricted NY-ESO-1-specific CD8+ single-positive T-cell clones functioned only in CD8+ T cells. Both 19305DP-TCR gene-engineered CD4+ and CD8+ T cells eliminated A*02+NY-ESO-1+ tumor xenografts in NSG mice. Finally, based on reactivity against a series of alanine-substituted peptides and a panel of normal human tissue-derived primary cells, 19305DP-TCR was predicted to have no cross-reactivity against any human non-NY-ESO-1 proteins. CONCLUSION: Together, our results indicate that the naturally occurring 19305DP-TCR derived from CD4+CD8+ double-positive αß T cells, is a promising therapeutic TCR gene for effective and safe adoptive T-cell therapy in A*02+ patients with NY-ESO-1-expressing tumor.

Reliability and validity of food portion size estimation from images using manual flexible digital virtual meshes.

OBJECTIVE: The eButton takes frontal images at 4s intervals throughout the day. A three-dimensional manually administered wire mesh procedure has been developed to quantify portion sizes from the two-dimensional images. The present paper reports a test of the inter-rater reliability and validity of use of the wire mesh procedure. DESIGN: Seventeen foods of diverse shapes and sizes served on plates, bowls and cups were selected to rigorously test the portion assessment procedure. A dietitian not involved in inter-rater reliability assessment used standard cups to independently measure the quantities of foods to generate the 'true' value for a total of seventy-five 'served' and seventy-five smaller 'left' images with diverse portion sizes. SETTING: The images appeared on the computer to which the digital wire meshes were applied. SUBJECTS: Two dietitians and three engineers independently estimated portion size of the larger ('served') and smaller ('left') images for the same foods. RESULTS: The engineers had higher reliability and validity than the dietitians. The dietitians had lower reliabilities and validities for the smaller more irregular images, but the engineers did not, suggesting training could overcome this limitation. The lower reliabilities and validities for foods served in bowls, compared with plates, suggest difficulties with the curved nature of the bowls. CONCLUSIONS: The wire mesh procedure is an important step forward in quantifying portion size, which has been subject to substantial self-report error. Improved training procedures are needed to overcome the identified problems.

Nutrition Education and Dietary Behavior Change Games: A Scoping Review.

Games provide an attractive venue for engaging participants and increasing nutrition-related knowledge and dietary behavior change, but no review has appeared devoted to this literature. A scoping review of nutrition education and dietary behavior change videogames or interactive games was conducted. A systematic search was made of PubMed, Agricola, and Google Scholar. Information was abstracted from 22 publications. To be included, the publication had to include a videogame or interactive experience involving games (a videogame alone, minigames inserted into a larger multimedia experience, or game as part of a human-delivered intervention); game's design objective was to influence dietary behavior, a psychosocial determinant of a dietary behavior, or nutrition knowledge (hereinafter referred to as diet-related); must have been reported in English and must have appeared in a professional publication, including some report of outcomes or results (thereby passing some peer review). This review was restricted to the diet-related information in the selected games. Diversity in targeted dietary knowledge and intake behaviors, targeted populations/audiences, game mechanics, behavioral theories, research designs, and findings was revealed. The diversity and quality of the research in general was poor, precluding a meta-analysis or systematic review. All but one of the studies reported some positive outcome from playing the game(s). One reported that a web-based education program resulted in more change than the game-based intervention. Studies of games may have been missed; a number of dietary/nutrition games are known for which no evaluation is known; and the data presented on the games and research were limited and inconsistent. Conclusions and Implications: A firmer research base is needed to establish the efficacy and effectiveness of nutrition education and dietary behavior change games.

Dietary Assessment with a Wearable Camera among Children: Feasibility and Intercoder Reliability.

BACKGROUND: The eButton, a multisensor device worn on the chest, uses a camera to passively capture images of everything in front of the child throughout the day. These images can be analyzed to provide a passive method of dietary intake assessment. OBJECTIVE: This study assessed the eButton's feasibility and intercoder reliability for dietary intake assessment. DESIGN: Children were recruited in the summer and fall of 2015, in Houston, TX, to wear the eButton to take 2 full days of dietary images, and the child-parent dyad participated in a following-day interview to verify what dietitians recorded from the images. PARTICIPANTS/SETTING: Thirty 9- to 13-year-old children participated during days convenient to them. MAIN OUTCOME MEASURES: Two dietitians independently manually reviewed the images to identify eating events, foods in those events, and portion sizes. STATISTICAL ANALYSES PERFORMED: Descriptive statistics of agreements and disagreements were calculated between dietitians and with children; t tests and Bland-Altman plots of differences in total kilocalories were calculated between dietitians and between initial dietitian estimates and those finalized after the verification interviews. RESULTS: The dietitians agreed on the identity of 60.5% of the 1,026 foods but disagreed on 28.6% of the foods and on the names for 10.8% of the foods. After the verification interviews, the dietitians agreed with the child-parent dyads on the identity of 77.0% of the 921 foods; the child-parent dyad identified 12.4% of the day's foods when images were not available or not clear; the child-parent dyad clarified that 5.4% of the foods identified were not consumed by the child; and the child-parent dyad clarified the identity of 5.2% of the foods. A software-based approach (three-dimensional wire mesh) could be used to estimate portion size on 24% of the foods, and professional judgment was required for 67.8%. Mean caloric intakes per day were not statistically significantly different between dietitians but were different between dietitians and child-parent dyads in total and on day 2. CONCLUSIONS: An early test of intercoder reliability of an all-day image method of dietary intake assessment obtained intercoder agreement between the two dietitians processing these images of intraclass correlation coefficient=0.67. A following-day verification interview with the child and parent was necessary to ensure completeness of estimates. Several feasibility problems occurred, which may be remedied with additional participant and dietitian training and further technological development.

Rapid Construction of Antitumor T-cell Receptor Vectors from Frozen Tumors for Engineered T-cell Therapy.

T cells genetically engineered with tumor antigen-specific T-cell receptor (TCR) genes have demonstrated therapeutic potential in patients with solid tumors. In order to achieve broader application, an efficient method to identify TCR genes for an array of tumor antigens and HLA restriction elements is required. Here, we have developed a method to construct a TCR-expression library from specimens, including frozen tumor biopsies, that contain antigen-specific T cells. TCR-expressing cassettes were constructed and cloned in a retroviral plasmid vector within 24 hours by unbiased PCR amplification of TCR α and ß chain variable regions assembled with TCR constant regions. The method was validated by constructing TCR-expressing vectors from tumor antigen-specific T-cell clones and functionally assessing TCR gene-transduced T cells. We applied this method to frozen ovarian tumor specimens that were infiltrated by tumor antigen-specific T cells. The tumor-derived TCR libraries were expressed in peripheral T cells from healthy volunteers and screened for tumor antigen-specific TCR pairs with the use of an MHC/peptide tetramer reagent. Tumor antigen-specific TCR-expressing transgenes were recovered from isolated tetramer-positive T cells. Peripheral T cells that were engineered with library-derived TCR gene showed potent therapeutic antitumor effect in a tumor xenograft model. Our method can efficiently and rapidly provide tumor-specific TCR-expressing viral vectors for the manufacture of therapeutic and personalized antitumor T-cell products. Cancer Immunol Res; 6(5); 594-604. ©2018 AACR.

Chronic cannabis use and attentional bias: Extended attentional capture to cannabis cues.

INTRODUCTION: A significant proportion of chronic cannabis users experience occupational, social, and psychological problems thought to reflect, in part, cannabis-related cognitive and emotional attentional biases. The emotional attentional blink (EAB) is a unique test of attentional bias that assesses automatic responses, cue-detection failures, and rapid and temporally extended biases. Using the EAB, we tested users' and non-users' attentional biases and how cannabis exposure correlates with these attentional biases. METHODS: Forty-eight regular cannabis users and 51 non-users completed demographic, psychological, and cannabis-use reports and two EAB target-detection experiments. Each experiment comprised 160 trials. Each trial included a rapid serial visual presentation of images with one of four types of distractor images (cannabis, generically positive, neutral, or scrambled) preceding the target image. Distractor images were presented 200ms (Lag 2) or 800ms (Lag 8) before the target in Experiment 1 and 200ms (Lag 2) or 500ms (Lag 5) before the target in Experiment 2. RESULTS: Chronic cannabis users exhibited exaggerated, immediate attentional bias (Lag 2) and exaggerated, extended attentional bias (Lag 5) compared to non-users. The intensity of cannabis-use (grams per week) correlated with more errors at the extended attentional bias durations (Lags 5 and 8). CONCLUSIONS: Our results represent novel evidence of automatic attentional capture consistent with an exaggerated "wanting" motive in models of addiction. Our unique evidence of temporally extended attentional biases is consistent with attentional disengagement deficits associated with chronic cannabis use.

Participant Outcomes from Methods of Recruitment for Videogame Research.

OBJECTIVE: The most productive methods of recruitment for a videogame for health (G4H) trial are not known. Success or failure of recruitment methods has been reported for a variety of clinical trials, but few specifically for G4H trials. This study's goal was to recruit 444 overweight or obese (body mass index percentile between the 84.5th-99.4th percentiles) children between the ages of 10-12 years. The article reports the results of different methods of participant recruitment. MATERIALS AND METHODS: Participants had to agree to three fasting blood samples (baseline, immediately after, and 2 months later); be willing to wear an accelerometer for 7 days at each assessment; read and speak English fluently (because the games were in English); have no history of any condition that would affect what he/she could eat or how much physical activity he/she could get; and have an eligible home computer purchased in the last 5 years with high-speed internet. Hardware criteria reflected the types of computers upon which Diab-Nano could be effectively played. Recruitment was conducted over a 35-month period and included electronic media, print advertising, community recruitment, and an internal volunteer list. Respondents were guided to a web-based screening questionnaire that asked for source of hearing about the study. RESULTS: Although diverse recruitment methods were used, slow recruitment resulted in obtaining only 45% of the recruitment goal (n = 199). Electronic media (e.g., radio, television, and internet), which reached millions of targeted parents, resulted in only 76 respondents, of whom 13 became participants; print media (e.g., magazine, newsletter/newspaper, and mail), which also reached large numbers of parents, resulted in 192 respondents, of whom 19 became participants; community recruitment (e.g., school, friend or family, doctors office, flyer, work, community program) resulted in 162 respondents, of whom 38 became participants; and the internal volunteer list resulted in 413 respondents, of whom 128 became participants. CONCLUSION: Inclusionary and exclusionary criteria and restricted access by gatekeepers could be deterrents to successful recruitment. The documented payoff of alternative comprehensive methods of recruitment should benefit other investigations in optimally allocating their recruitment resources.

Assessment of barriers to improve diabetes management in older adults: a randomized controlled study.

OBJECTIVE: To evaluate whether assessment of barriers to self-care and strategies to cope with these barriers in older adults with diabetes is superior to usual care with attention control. The American Diabetes Association guidelines recommend the assessment of age-specific barriers. However, the effect of such strategy on outcomes is unknown. RESEARCH DESIGN AND METHODS: We randomized 100 subjects aged ≥69 years with poorly controlled diabetes (A1C >8%) in two groups. A geriatric diabetes team assessed barriers and developed strategies to help patients cope with barriers for an intervention group. The control group received equal amounts of attention time. The active intervention was performed for the first 6 months, followed by a "no-contact" period. Outcome measures included A1C, Tinetti test, 6-min walk test (6MWT), self-care frequency, and diabetes-related distress. RESULTS: We assessed 100 patients (age 75 ± 5 years, duration 21 ± 13 years, 68% type 2 diabetes, 89% on insulin) over 12 months. After the active period, A1C decreased by -0.45% in the intervention group vs. -0.31% in the control group. At 12 months, A1C decreased further in the intervention group by -0.21% vs. 0% in control group (linear mixed-model, P < 0.03). The intervention group showed additional benefits in scores on measures of self-care (Self-Care Inventory-R), gait and balance (Tinetti), and endurance (6MWT) compared with the control group. Diabetes-related distress improved in both groups. CONCLUSIONS: Only attention between clinic visits lowers diabetes-related distress in older adults. However, communication with an educator cognizant of patients' barriers improves glycemic control and self-care frequency, maintains functionality, and lowers distress in this population.

Self-efficacy in service-learning community action research: theory, research, and practice.

The purpose of this article is threefold: In the first section, an overview of research and theory on the self-efficacy construct is provided, and the central role of self-efficacy in service-learning community action research is demonstrated. The second section reviews over 10 years of research validating the Community Service Self-Efficacy Scale (CSSES), which measures the individual's confidence in his or her own ability to make clinically (meaningfully) significant contributions to the community through service. Within the context of this review, recent (previously unpublished) validation research is also reviewed. Alternate versions of the CSSES, each of which was developed for a specific purpose, are presented. The third section provides recommendations for further research focused on (a) validating the CSSES and (b) examining self-efficacy as an outcome, moderator, and mediating variable in service-learning community action research.

Regulatory T cell-mediated transplantation tolerance.

The existence of naturally occurring regulatory T cells in normal hosts and their pivotal role in maintaining both auto- and allo-tolerance have direct implications on the therapy of autoimmune disorders and for achieving immunosuppression-free allotransplantation. Among the various forms of regulatory T cells described, CD4(+)CD25(+) T cells have emerged as one of the most potent tolerogenic subsets. In this review, we discuss the molecular basis of development and function of these regulatory T cells and their potential role in the context of chronic lung allograft rejection.