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While immune checkpoint inhibition is rapidly becoming standard of care in many solid tumors, immune checkpoint inhibitors (ICIs) fail to induce clinical responses in many patients, presumably due to insufficient numbers of tumor-specific T cells in the tumor milieu. To this end, immunization protocols using viral vectors expressing tumor-associated antigens are being explored to induce T cell responses that synergize with ICIs. However, the optimal combination of vaccine and immune checkpoint regimen remains undefined. Here, a dendritic cell-targeting lentiviral vector (ZVex®) expressing the endogenous murine tyrosinase-related protein 1 (mTRP1), or the human tumor antigen NY-ESO-1, was explored as monotherapy or heterologous prime-boost (HPB) vaccine regimen together with recombinant tumor antigen in the murine B16 melanoma model. PD1/PDL1 blockade significantly enhanced ZVex/mTRP1, but not ZVex/NY-ESO-1, induced immune responses in mice, whereas the opposite effect was observed with anti-CTLA4 antibody. Anti-tumor efficacy of anti-PD1, but not anti-PDL1 or anti-CTLA4, was significantly enhanced by ZVex/mTRP1 and HPB vaccination. These results suggest mechanistic differences in the effect of checkpoint blockade on vaccine-induced immune and anti-tumor responses against self versus non-self tumor antigens, possibly due to tolerance and state of exhaustion of anti-tumor T cells.

Systemic interleukin-12 (IL12) anti-tumor therapy is highly potent but has had limited utility in the clinic due to severe toxicity. Here, we present two IL12-expressing vector platforms, both of which can overcome the deficiencies of previous systemic IL12 therapies: 1) an integrating lentiviral vector, and 2) a self-replicating messenger RNA formulated with polyethyleneimine. Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Furthermore, concurrent intratumoral administration of the synthetic TLR4 agonist glucopyranosyl lipid A formulated in a stable emulsion (GLA-SE) induced systemic memory T cell responses that mediated complete protection against tumor rechallenge in all survivor mice (8/8 rechallenged mice), whereas only 2/6 total rechallenged mice treated with intratrumoral IL12 monotherapy rejected the rechallenge. Taken together, expression of vectorized IL12 in combination with a TLR4 agonist represents a varied approach to broaden the applicability of intratumoral immune therapies of solid tumors.

Currently, 34% of U.S. adults are obese.1 The U.S. Preventive Services Task Force recommends that all adults with a body mass index ≥ 30 kg/m2 be offered intensive counseling for weight loss, or be referred to programs that offer it.2 However, it is not practical to provide intensive counseling to such a large number of individuals. If patient selection could be improved, weight loss programs might achieve lower attrition rates and improved weight losses. The NIH guidelines on evaluation and treatment of obesity state that readiness for weight loss should be assessed in persons presenting for treatment, while noting that such assessment is “easier said than done.”3 However, a recent review challenged the notion that weight loss readiness – a person’s self-reported desire and willingness to make changes to lose weight – is important to assess in clinical settings.4 Self-reported readiness, the review concluded, predicted neither treatment adherence nor the magnitude of weight loss among persons pursuing a variety of weight control methods. The authors suggested that the lack of significant findings may be a function of the limited range of readiness among people who voluntarily engage in weight loss programs. Another explanation may be the limitation of self-report assessments of readiness. Individuals may overestimate their readiness because they do not clearly understand what behaviors are needed to make them successful, or because they greatly desire the outcome of weight loss. We examined the ability of a behavioral task at screening to predict weight loss, session attendance, and physical activity at 1 year among participants who received an intensive lifestyle intervention in the Look AHEAD study.5 Look AHEAD’s careful screening procedures included a 2-week run-in period, in which candidates were required to record (but not required to alter) their food intake for at least 12 of 14 days.6 Look AHEAD investigators believed that participants’ keeping food records during the run-in would predict record keeping during treatment. Keeping food records during treatment, in turn, is positively correlated with weight loss.7–12 Thus, in the current study, we assessed performance of a specific behavior, expected to be related to weight loss, rather than asking about general readiness to lose weight. We specifically sought to determine whether the completeness of record keeping during the screening period would predict weight loss outcomes at 1 year.

O1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cells #### Andreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1

Behavior change theories and models, validated within the field of dietetics, offer systematic explanations for nutrition-related behavior change. They are integral to the nutrition care process, guiding nutrition assessment, intervention, and outcome evaluation. The American Dietetic Association Evidence Analysis Library Nutrition Counseling Workgroup conducted a systematic review of peer-reviewed literature related to behavior change theories and strategies used in nutrition counseling. Two hundred fourteen articles were reviewed between July 2007 and March 2008, and 87 studies met the inclusion criteria. The workgroup systematically evaluated these articles and formulated conclusion statements and grades based upon the available evidence. Strong evidence exists to support the use of a combination of behavioral theory and cognitive behavioral theory, the foundation for cognitive behavioral therapy (CBT), in facilitating modification of targeted dietary habits, weight, and cardiovascular and diabetes risk factors. Evidence is particularly strong in patients with type 2 diabetes receiving intensive, intermediate-duration (6 to 12 months) CBT, and long-term (>12 months duration) CBT targeting prevention or delay in onset of type 2 diabetes and hypertension. Few studies have assessed the application of the transtheoretical model on nutrition-related behavior change. Little research was available documenting the effectiveness of nutrition counseling utilizing social cognitive theory. Motivational interviewing was shown to be a highly effective counseling strategy, particularly when combined with CBT. Strong evidence substantiates the effectiveness of self-monitoring and meal replacements and/or structured meal plans. Compelling evidence exists to demonstrate that financial reward strategies are not effective. Goal setting, problem solving, and social support are effective strategies, but additional research is needed in more diverse populations. Routine documentation and evaluation of the effectiveness of behavior change theories and models applied to nutrition care interventions are recommended.

The prevalence of childhood overweight has increased significantly, with the highest rates noted among Mexican Americans. Many negative health outcomes are associated with overweight; thus, there is a need for effective weight-loss interventions tailored to this group. This study evaluated 24-month outcomes of a randomized, controlled trial involving an intensive lifestyle-based weight maintenance program targeting overweight Mexican-American children at a charter school in Houston, Texas. A total of 60 children (33 males, 55%) between the ages of 10 and 14 at or >85th percentile for BMI were recruited. Participants were randomized to an instructor-led intervention (ILI) or a self-help (SH) program, both aimed at modifying eating and physical activity behaviors using behavior modification strategies. Changes in participants' standardized BMI (zBMI) were assessed at baseline, 1, and 2 years. Tricep skinfold, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and calculated low-density lipoprotein were assessed at baseline and 1 year. ILI participants showed significantly greater decreases in zBMI at 1 and 2 years (F = 26.8, P < 0.001, F = 4.1, P < 0.05, respectively) compared to SH controls. ILI participants showed greater improvements in body composition, as measured by tricep skinfold (F = 9.75, P < 0.01). Children in the ILI condition experienced benefits with respect to total cholesterol (F = 7.19, P < 0.05) and triglycerides (F = 4.35, P < 0.05) compared to children in the SH condition. Overall, the school-based intervention resulted in improved weight and clinical outcomes in overweight Mexican-American children, and zBMI was maintained over 2 years.

Purpose. Consumer understanding of nutrition information is key to making dietary choices consistent with guidelines. The development of an objective, science-based, and universally applicable system of nutrition guidance would be of considerable potential value to the public health. Design. A multidisciplinary expert panel was convened to develop the Overall Nutritional Quality Index (ONQI). Dietary guidelines, existing nutritional scoring systems, and other pertinent scientific literature were reviewed. An algorithm based on the overall nutritional quality of food was developed and subjected to consumer research and validation testing. Results. The ONQI algorithm incorporates over 30 entries representing both micronutrient and macronutrient properties of foods, as well as weighting coefficients representing epidemiologic associations between nutrients and health outcomes. The basic entry in the algorithm is a weighted trajectory score, which compares nutrient concentration in a food to the recommended concentration of a given nutrient in a healthful diet. In content validity testing, ONQI rankings and expert panel rankings correlated highly (R = .92; p < .001). In regression analysis, aggregated ONQI scores for total diet corresponded well with the Healthy Eating Index (p < .001) in the National Health and Nutrient Examination Survey 2003–2006 cohort (n = 15,900). Consumer research indicated strong appeal to consumers of the ONQI system in general, and the scores on a 1 to 100 scale specifically. A system for acquiring nutrient data, meeting U.S. Food and Drug Administration and U.S. Department of Agriculture standards, has been established so that virtually any food, beverage, meal, or recipe can be scored. Conclusions. The ONQI is a sophisticated nutrition guidance system developed by a multidisciplinary group independently of all food industry interests with excellent initial performance in both consumer research and validation testing. Combined with a consumer education program, the ONQI has considerable potential to improve dietary patterns, and consequently the public health. Prospective study of effects on dietary patterns and health outcomes is warranted.

Abstract Many protocols have been used in clinical and research settings for collecting systolic blood pressure (SBP) measurements to calculate the ankle–brachial index (ABI); however, it is not known how useful it is to replicate measurements and which measures best reflect cardiovascular risk. Standardized measurements of ankle and arm SBP from 5140 overweight or obese individuals with type 2 diabetes were used to estimate sources of variation. Measurement characteristics of leg-specific ABI, as calculated using a standard algorithm based on the highest SBP of the dorsalis pedis or posterior tibial arteries, were projected using simulations. Coefficients of variability ranged from 2% to 3% when single SBP measurements were used and ABI was overestimated by 2–3%. Taking two SBP measurements at each site reduced standard errors and bias each by 30–40%. The sensitivity of detecting low ABI ranges exceeded 90% for ABI within 0.05 of the 0.90 clinical cut-point. The average and the minimum of the two (i.e. right and left) leg-specific ABI values had similar U-shaped relationships with Framingham risk scores; however, the average leg ABI had slightly greater precision. Replicating SBP measurements reduces the error and bias of ABI. Averaging leg-specific values may increase power for characterizing cardiovascular disease risk.

OBJECTIVE—The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes 1-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events. RESEARCH DESIGN AND METHODS—This study consisted of a multicentered, randomized, controlled trial of 5,145 individuals with type 2 diabetes, aged 45–74 years, with BMI >25 kg/m2 (>27 kg/m2 if taking insulin). An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition. RESULTS—Participants assigned to ILI lost an average 8.6% of their initial weight vs. 0.7% in DSE group (P < 0.001). Mean fitness increased in ILI by 20.9 vs. 5.8% in DSE (P < 0.001). A greater proportion of ILI participants had reductions in diabetes, hypertension, and lipid-lowering medicines. Mean A1C dropped from 7.3 to 6.6% in ILI (P < 0.001) vs. from 7.3 to 7.2% in DSE. Systolic and diastolic pressure, triglycerides, HDL cholesterol, and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants (all P < 0.01). CONCLUSIONS—At 1 year, ILI resulted in clinically significant weight loss in people with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk.

To evaluate whether snacking would improve weight loss and weight maintenance in overweight individuals within the context of a structured meal replacement (MR) weight loss program. A prospective 24 week, 2 (snacking vs nonsnacking) × 2 (MR vs meal replacement augmented with snacks (MRPS)) randomized trial. Participants were instructed to limit their total daily intake to 1200 (women) or 1500 (men) kcals. Those receiving the MR program were instructed not to snack while those in the MRPS program were told to snack three times per day. A total of 100 participants were block-randomized, based on prestudy snacking status (high vs low), to receive a standard meal replacement program (MR) or MRPS. Weight, height, blood pressure, lipid fractions, glucose, and insulin were assessed at the baseline, 12-, and 24 weeks. Completers analysis at 24 weeks demonstrated a significant time effect (F(1,46)=44.6, P

Because of the increased risk of comorbid conditions such as type 2 diabetes, hypertension, and osteoarthritis, and the high health care costs associated with obesity, researchers and clinicians continually search for low-cost and effective treatments for weight loss and weight maintenance. In this article we provide an overview of the principles of behavior modification as applied to the treatment of obesity, examine the benefits of augmenting behavioral interventions with pharmacotherapy, and review the use of less-traditional applications of behavior modification in the treatment of obesity, specifically Internet interventions, meal replacements, and telephone interventions. Based on our review, we conclude that these less-traditional approaches can be used effectively to apply the principles of behavior modification, specifically stimulus control and self-monitoring, to obese patients. Future directions for research are outlined, which include examining the use of nontraditional behavioral interventions with children and the development of culturally sensitive interventions for racial and ethnic minority populations.

The stimulatory NKG2D receptor on lymphocytes promotes tumor immune surveillance by targeting ligands selectively induced on cancer cells. Progressing tumors counteract by employing tactics to disable lymphocyte NKG2D. This negative dynamic is escalated as some human cancer cells co-opt expression of NKG2D, thereby complementing the presence of its ligands for autonomous stimulation of oncogenic signaling. Clinical association data imply relationships between cancer cell NKG2D and metastatic disease. Here we show that NKG2D promotes cancer cell plasticity by induction of phenotypic, molecular, and functional signatures diagnostic of the epithelial-mesenchymal transition, and of stem-like traits via induction of Sox9, a key transcriptional regulator of breast stem cell maintenance. These findings obtained with model breast tumor lines and xenotransplants were recapitulated by ex vivo cancer cells from primary invasive breast carcinomas. Thus, NKG2D may have the capacity to drive high malignancy traits underlying metastatic disease.

Background Little is known about diet quality with a reduced-energy, low-fat, partial meal replacement plan, especially in individuals with type 2 diabetes. The Action for Health in Diabetes (Look AHEAD) trial implemented a partial meal replacement plan in the Intensive Lifestyle Intervention. Objective To compare dietary intake and percent meeting fat-related and food group dietary recommendations in Intensive Lifestyle Intervention and Diabetes Support and Education groups at 12 months. Design A randomized controlled trial comparing Intensive Lifestyle Intervention with Diabetes Support and Education at 0 and 12 months. Participants/setting From 16 US sites, the first 50% of participants (aged 45 to 76 years, overweight or obese, with type 2 diabetes) were invited to complete dietary assessments. Complete 0- and 12-month dietary assessments (collected between 2001 and 2004) were available for 2,397 participants (46.6% of total participants), with 1,186 randomized to Diabetes Support and Education group and 1,211 randomized to Intensive Lifestyle Intervention group. Main outcome measures A food frequency questionnaire assessed intake: energy; percent energy from protein, fat, carbohydrate, polyunsaturated fatty acids, and saturated fats; trans -fatty acids; cholesterol; fiber; weekly meal replacements; and daily servings from food groups from the Food Guide Pyramid. Statistical analyses performed Mixed-factor analyses of covariance, using Proc MIXED with a repeated statement, with age, sex, race/ethnicity, education, and income controlled. Unadjusted χ 2 tests compared percent meeting fat-related and food group recommendations at 12 months. Results At 12 months, Intensive Lifestyle Intervention participants had a significantly lower fat and cholesterol intake and greater fiber intake than Diabetes Support and Education participants. Intensive Lifestyle Intervention participants consumed more servings per day of fruits; vegetables; and milk, yogurt, and cheese; and fewer servings per day of fats, oils, and sweets than Diabetes Support and Education participants. A greater percentage of Intensive Lifestyle Intervention participants than Diabetes Support and Education participants met fat-related and most food group recommendations. Within Intensive Lifestyle Intervention, a greater percentage of participants consuming two or more meal replacements per day than participants consuming less than one meal replacement per day met most fat-related and food group recommendations. Conclusions The partial meal replacement plan consumed by Intensive Lifestyle Intervention participants was related to superior diet quality.

Look AHEAD (Action for Health in Diabetes) was a randomized clinical trial designed to examine the long-term health effects of weight loss in overweight and obese individuals with type 2 diabetes. The primary result was that the incidence of cardiovascular events over a median follow-up of 9.6 years was not reduced in the Intensive Lifestyle Group relative to the control group. This finding is discussed, with emphasis on its implications for design of trials and clinical treatment of obese persons with type 2 diabetes.

OBJECTIVE: To evaluate a culturally appropriate intervention to increase activity in overweight Mexican American women. METHODS: Participants were randomly assigned to a physical activity program or wait-list control. RESULTS: Treated participants were not more active than controls at 6 or 12 months. In addition, we found no significant differences in the proportion of individuals who met an objective criterion for physical activity from baseline to 6 months in the treatment or control groups. CONCLUSION: The intervention did not increase physical activity in this population. Differences in baseline activity and contamination of the control group may partially account for the outcome.

OBJECTIVE To examine usual marine ω-3 fatty acid (mO-3FA) intake in individuals with diabetes; its association with adiposity, lipid, and glucose control; and its changes with behavioral lifestyle intervention for weight loss. RESEARCH DESIGN AND METHODS Cross-sectional and 1-year longitudinal analyses were performed on 2,397 Look AHEAD (Action for Health in Diabetes) participants. Look AHEAD is a cardiovascular outcome trial evaluating the effects of intensive lifestyle intervention for weight loss in overweight/obese subjects with type 2 diabetes. RESULTS Baseline mO-3FA intake was 162 ± 138 mg/day. It was inversely associated with triglycerides (β = −0.41, P < 0.001) and weakly with HDL (β = 4.14, P = 0.050), after multiple covariate adjustment. One-year mO-3FA and fried/sandwich fish intake decreased with intensive lifestyle intervention (P < 0.001). CONCLUSIONS mO-3FA intake in Look AHEAD participants was low but associated favorably with lipids. These results encourage investigation on the potential benefits of increasing mO-3FA intake in lifestyle interventions for weight loss in individuals with diabetes.

Objective In treatment of binge eating, measures of self-concept, eating self-efficacy, and social support were examined at 0, 6, and 18 months to determine if improvements in these variables were associated with reductions in binge eating severity. Method Obese adult females (N = 125) were treated for 6 months, with 12 months of maintenance meetings. The Binge Eating Scale (BES), Tennessee Self-Concept Scale (TSC), Dieter's Inventory of Eating Temptations (DIET), and a social support measure (SocSup) were used. Results Over the first 6 months, improvements in BES were associated with improvements in the TSC and DIET. Over 18 months, improvements in BES were associated with improvements in the TSC, DIET, and SocSup. Discussion Therapy for binge eating should result in improvement in self-concept and eating self-efficacy, as well as reductions in binge eating. This study showed that self-concept and eating self-efficacy were associated with improvement in binge eating severity. The association with social support did not appear until long-term follow-up. Improvement in self-concept and eating self-efficacy may be processes leading to clinical improvement in this eating disorder, or they may result from changes in binge eating. © 1999 by John Wiley & Sons, Inc. Int J Eat Disord 26: 295–300, 1999.

Predicting outcome in weight loss trials from baseline characteristics has proved difficult. Readiness to change is typically measured by self-report.Performance of a behavioral task, completion of food records, from the screening period in the Look AHEAD study (n = 549 at four clinical centers) was assessed. Completeness of records was measured by the number of words and Arabic numerals (numbers) recorded per day, the number of eating episodes per day, and days per week where physical activity was noted. The primary outcome was weight loss at one year.In univariable analysis, both the number of words recorded and the number of numbers recorded were associated with greater weight loss. In multivariable analysis, individuals who recorded 20-26, 27-33, and ≥34 words per day lost 9.12%, 11.40%, and 12.08% of initial weight, compared to 8.98% for individuals who recorded less than 20 words per day (P values of 0.87, 0.008, and0.001, respectively, compared to20 words per day).Participants who kept more detailed food records at screening lost more weight after 1 year than individuals who kept sparser records. The use of objective behavioral screening tools may improve the assessment of weight loss readiness.

The stimulatory NKG2D lymphocyte receptor together with its tumor-associated ligands enable the immune system to recognize and destroy cancer cells. However, with dynamic changes unfolding, cancers exploit NKG2D and its ligands for immune evasion and suppression. Recent findings have added yet another functional dimension, wherein cancer cells themselves co-opt NKG2D for their own benefit to complement the presence of its ligands for self-stimulation of parameters of tumorigenesis. Those findings are here extended to in vivo tumorigenicity testing by employing orthotopic xenotransplant breast cancer models in mice. Using human cancer lines with ectopic NKG2D expression and RNA interference (RNAi)-mediated protein depletion among other controls, we show that NKG2D self-stimulation has tumor-promoting capacity. NKG2D signals had no notable effects on cancer cell proliferation and survival but acted at the level of angiogenesis, thus promoting tumor growth, tumor cell intravasation and dissemination. NKG2D-mediated effects on tumor initiation may represent another factor in the observed overall enhancement of tumor development. Altogether, these results may have an impact on immunotherapy approaches, which currently do not account for such NKG2D effects in cancer patients and thus could be misdirected as underlying assumptions are incomplete.

Background: transFatty acids (TFAs) increase cardiovascular disease risk. TFAs and polyunsaturated fatty acids (PUFAs) in the food supply may be declining with reciprocal increases in cis-monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs). Objectives: We sought to determine whether plasma 18-carbon TFA and PUFA concentrations might decrease over time and whether there might be reciprocal increases in plasma cis-MUFAs and SFAs. Design: We studied 305 persons (171 women) taking part in Look AHEAD (Action for Health in Diabetes), a randomized trial of lifestyle intervention for weight loss to reduce major cardiovascular events in overweight and obese adults (aged 45–76 y) with type 2 diabetes who also participated in an ancillary study of oxidative stress. This study was a cross-sectional analysis of TFAs, cis-MUFAs, SFAs, and PUFAs measured in plasma before intervention (September 2002–April 2004). Results: In a model that included demographic characteristics, plasma total fatty acid concentration, BMI, serum insulin, statin use, season, and longitudinal time trend (R2 = 0.167, P < 0.0001), plasma TFAs decreased by 13.5%/y (95% CI: −22.7, −3.2%/y; absolute decrease 7.0 mg · L−1 · y−1; 95% CI: −12.5, −1.6 mg · L−1 · y−1; P = 0.012). This longitudinal trend was not significantly altered by further adjustment for dietary variables and physical activity. In contrast, longitudinal trends for PUFAs, cis-MUFAs, and SFAs were weak and not significant. Conclusions: This change in plasma concentrations of TFAs is consistent with changes in fatty acid composition that food manufacturers are likely to have made to avoid declaring TFAs on food labels. Further research will be needed to determine the overall effect of these changes on cardiovascular risk. The Look AHEAD trial is registered at clinicaltrials.govas {"type":"clinical-trial","attrs":{"text":"NCT00017953","term_id":"NCT00017953"}}NCT00017953.

Objective The effects of three cognitive-behavioral weight control interventions for adults were compared: diet only, exercise only, and a combination of diet and exercise. This article reports 2-year follow-up data. Design The three interventions were compared in a randomized, experimental design. Subjects A total of 127 men and women who were at least 14 kg overweight (according to height-weight tables) were recruited from an urban community and assigned randomly to the experimental conditions. Intervention The dietary intervention was a low-energy eating plan adjusted to produce a 1 kg/week loss of weight. The exercise component involved training in walking and a home-based program of up to five exercise periods per week. There were 12 weekly instructional sessions, followed by 3 biweekly and 8 monthly meetings. All sessions were led by registered dietitians. Outcome measures Changes in body weight. Statistical analyses Analysis of variance for weight changes and repeated measures analysis of variance for weight change trends. Results At 1 year, no significant differences were noted among the three groups. The diet-only group lost 6.8 kg, the exercise-only group lost 2.9 kg, and the combination group lost 8.9 kg ( P =.09). During the second year, the diet-only group regained weight — reaching 0.9 kg above baseline; the combination group regained to 2.2 kg below baseline; and the exercise-only group regained slightly to 2.7 kg below baseline ( P =.36). Repeated measures analysis of variance showed a group-by-time interaction ( P =.001); data for the dieting groups best fit a U-shaped regain curve ( P =.001). Applications The results suggest that dieting is associated with weight loss followed by regain after treatment ends, whereas exercise alone produced smaller weight losses but better maintenance. The large outcome variability and unequal difficulty of the regimens across groups limit the generalizability of the findings. J Am Diet Assoc. 1996; 96:342-346 .

The stimulatory natural killer group 2 member D (NKG2D) lymphocyte receptor and its tumor-associated ligands are important mediators in the immune surveillance of cancer. With advanced human tumors, however, persistent NKG2D ligand expression may favor tumor progression. We have found that cancer cells themselves express NKG2D in complex with the DNAX-activating protein 10 (DAP10) signaling adaptor. Triggering of NKG2D on ex vivo cancer cells or on tumor lines which express only few receptor complexes activates the oncogenic PI3K–protein kinase B (PKB/AKT)–mammalian target of rapamycin (mTOR) signaling axis and downstream effectors, the ribosomal protein S6 kinase 1 (S6K1) and the translation initiation factor 4E-binding protein 1 (4E-BP1). In addition, as in lymphocytes, NKG2D ligand engagement stimulates phosphorylation of JNK and ERK in MAP kinase cascades. Consistent with these signaling activities, above-threshold expression of NKG2D–DAP10 in a ligand-bearing tumor line increases its bioenergetic metabolism and proliferation, thus suggesting functional similarity between this immunoreceptor and tumor growth factor receptors. This relationship is supported by significant correlations between percentages of cancer cells that are positive for surface NKG2D and criteria of tumor progression. Hence, in a conceptual twist, these results suggest that tumor co-option of NKG2D immunoreceptor expression may complement the presence of its ligands for stimulation of tumor growth.

Alcohol intake and exercise have both been found to be related to increased plasma levels of high density lipoprotein cholesterol (HDLC). Exercise training results in decreased postprandial lipemia, and clearance rate of infused lipids is related to plasma lipoprotein levels in physically active men. The effect of alcohol intake on plasma triglyceride (TG) clearance has not been studied in relation to the exercise status of subjects. Plasma TG change over 8 h was determined following a liquid fatty meal in 14 male habitual runners (R) and 13 physically inactive men (I) after 3 weeks of alcohol abstinence and 3 weeks of drinking ∼41 g(1.44 oz) of ethanol per day. Fasting total cholesterol and apolipoprotein A-1 (apo A-1) were not different between groups, but TG was lower and HDLC, HDL 2 C, and HDL3C were higher in the runners. After abstinence, I had slower TG clearance ( P = 0.07) compared with R; with alcohol, TG clearance was unchanged in R, but was significantly retarded in I. With alcohol, both groups had increased HDLC levels, but this mainly was due to an increase in HDL 3 C in R and HDL 2 C in I; apo A-1 increased similarly in both groups and fasting TG increased significantly only in I. Alcohol-induced increases in postprandial lipemia and retardation of TG clearance appear to occur in inactive, but not exercise-trained subjects and the effect of alcohol on plasma HDL subfractions may differ between these groups.

The effects of a behavior modification program were studied in a free-living population of mildly obese adults over a one-year period. A total of 165 subjects were randomly assigned to control or to exercise-only, diet-only, or exercise-plus-diet behavior modification groups. The diet plan consisted of a prudent, reduced-fat regimen. Most subjects chose brisk walking for exercise. After the first 3 months, diet intervention was associated with a significant reduction in weight, percent body fat, and waist circumference. After 12 months, mean weight of the exercise-plus-diet group was lower than that of the exercise-only group. Interpretation of these results is difficult, because many of the subjects failed to adhere to the behavioral recommendations. Problems in treating obese adults without close therapist scrutiny are discussed.

Background Recommendations for daily dietary vegetable intake were increased in the 2005 USDA Dietary Guidelines as consumption of a diet rich in vegetables has been associated with lower risk of certain chronic health disorders including cardiovascular disease. However, vegetable consumption in the United States has declined over the past decade; consequently, the gap between dietary recommendations and vegetable intake is widening. The primary aim of this study is to determine if drinking vegetable juice is a practical way to help meet daily dietary recommendations for vegetable intake consistent with the 2005 Dietary Guidelines and the Dietary Approaches to Stop Hypertension (DASH) diet. The secondary aim is to assess the effect of a vegetable juice on measures of cardiovascular health. Methods We conducted a 12-week, randomized, controlled, parallel-arm study consisting of 3 groups of free-living, healthy volunteers who participated in study visits at the Ragle Human Nutrition Research Center at the University of California, Davis. All subjects received education on the DASH diet and 0, 8 or 16 fluid ounces of vegetable juice daily. Assessments were completed of daily vegetable servings before and after incorporation of vegetable juice and cardiovascular health parameters including blood pressure. Results Without the juice, vegetable intake in all groups was lower than the 2005 Dietary Guidelines and DASH diet recommendations. The consumption of the vegetable juice helped participants reach recommended intake. In general, parameters associated with cardiovascular health did not change over time. However, in the vegetable juice intervention groups, subjects who were pre-hypertensive at the start of the study showed a significant decrease in blood pressure during the 12-week intervention period. Conclusion Including 1-2 cups of vegetable juice daily was an effective and acceptable way for healthy adults to close the dietary vegetable gap. Increase in daily vegetable intake was associated with a reduction in blood pressure in subjects who were pre-hypertensive at the start of the trial. Trial Registration Clinicaltrials.gov NCT01161706

Despite the health benefits, vegetable intake in youth remains below recommended levels. The purpose of our study was to compare two methods for increasing vegetable consumption. It was hypothesized that participants randomized to both the exposure-only and the pairing condition would increase their vegetable consumption and increase the variety of vegetables consumed. A total of 78 Mexican-American middle school-aged children from a charter school in Houston, TX, were randomized to a pairing condition (n=40) or an exposure-only condition (n=38) during the Spring 2009 semester. Children in the pairing condition were provided a preferred taste (peanut butter) paired with vegetables weekly at school during a nutrition class for 4 months. Children in the exposure-only condition received vegetables weekly during a nutrition class that covered the same material as the pairing condition. After 4 months, the pairing condition participants demonstrated significant increases in vegetable consumption (F=13.40, P

Background Metabolic syndrome, a constellation of metabolic risk factors for type 2 diabetes and cardiovascular disease, is one of the fastest growing disease entities in the world. Weight loss is thought to be a key to improving all aspects of metabolic syndrome. Research studies have suggested benefits from diets rich in vegetables and fruits in helping individuals reach and achieve healthy weights. Objective To evaluate the effects of a ready to serve vegetable juice as part of a calorie-appropriate Dietary Approaches to Stop Hypertension (DASH) diet in an ethnically diverse population of people with Metabolic Syndrome on weight loss and their ability to meet vegetable intake recommendations, and on their clinical characteristics of metabolic syndrome (waist circumference, triglycerides, HDL, fasting blood glucose and blood pressure). A secondary goal was to examine the impact of the vegetable juice on associated parameters, including leptin, vascular adhesion markers, and markers of the oxidative defense system and of oxidative stress. Methods A prospective 12 week, 3 group (0, 8, or 16 fluid ounces of low sodium vegetable juice) parallel arm randomized controlled trial. Participants were requested to limit their calorie intake to 1600 kcals for women and 1800 kcals for men and were educated on the DASH diet. A total of 81 (22 men & 59 women) participants with Metabolic Syndrome were enrolled into the study. Dietary nutrient and vegetable intake, weight, height, leptin, metabolic syndrome clinical characteristics and related markers of endothelial and cardiovascular health were measured at baseline, 6-, and 12-weeks. Results There were significant group by time interactions when aggregating both groups consuming vegetable juice (8 or 16 fluid ounces daily). Those consuming juice lost more weight, consumed more Vitamin C, potassium, and dietary vegetables than individuals who were in the group that only received diet counseling (p < 0.05). Conclusion The incorporation of vegetable juice into the daily diet can be a simple and effective way to increase the number of daily vegetable servings. Data from this study also suggest the potential of using a low sodium vegetable juice in conjunction with a calorie restricted diet to aid in weight loss in overweight individuals with metabolic syndrome.

OBJECTIVE To examine usual marine ω-3 fatty acid (mO-3FA) intake in individuals with diabetes; its association with adiposity, lipid, and glucose control; and its changes with behavioral lifestyle intervention for weight loss. RESEARCH DESIGN AND METHODS Cross-sectional and 1-year longitudinal analyses were performed on 2,397 Look AHEAD (Action for Health in Diabetes) participants. Look AHEAD is a cardiovascular outcome trial evaluating the effects of intensive lifestyle intervention for weight loss in overweight/obese subjects with type 2 diabetes. RESULTS Baseline mO-3FA intake was 162 ± 138 mg/day. It was inversely associated with triglycerides (β = −0.41, P < 0.001) and weakly with HDL (β = 4.14, P = 0.050), after multiple covariate adjustment. One-year mO-3FA and fried/sandwich fish intake decreased with intensive lifestyle intervention (P < 0.001). CONCLUSIONS mO-3FA intake in Look AHEAD participants was low but associated favorably with lipids. These results encourage investigation on the potential benefits of increasing mO-3FA intake in lifestyle interventions for weight loss in individuals with diabetes.

Objective: Excess adiposity is associated with systemic low-grade inflammation, which has been implicated in the pathophysiology of various diseases. The purpose of this study was to examine the relation between measures of adiposity and disease risk factors in Mexican American children participating in a weight loss intervention. Subjects and Methods: Boys and girls (N = 170; 13.3 ±0.1 year) volunteered for additional testing from a larger study that demonstrated significant reduction in standardized body mass index. Insulin, C-reactive protein, soluble cluster of differentiation 14, glucose, and cholesterol profile were assessed. Results: Linear mixed models regression showed that changes in adiposity (standardized body mass index and triceps skinfold) were significantly related with changes in total cholesterol (P=0.01), triglycerides (P < 0.001), C-reactive protein (P < 0.001 ), insulin (P < 0.001 ), Homeostasis model assessment of insulin resistance (P < 0.001), and high-density lipoprotein (P < 0.001). Conclusions: The relation between measures of adiposity and disease risk factors was stable over time in children participating in an exercise/weight loss intervention. Also, our findings indicate that reducing adiposity results in an improvement of blood disease risk factors in Mexican American children.

It is the position of the American Dietetic Association that successful weight management to improve overall health for adults requires a lifelong commitment to healthful lifestyle behaviors emphasizing sustainable and enjoyable eating practices and daily physical activity. Given the increasing incidence of overweight and obesity along with the escalating health care costs associated with weight-related illnesses, health care providers must discover how to effectively treat this complex condition. Food and nutrition professionals should stay current and skilled in weight management to assist clients in preventing weight gain, optimizing individual weight loss interventions, and achieving long-term weight loss maintenance. Using the American Dietetic Association's Evidence Analysis Process and Evidence Analysis Library, this position paper presents the current data and recommendations for weight management. The evidence supporting the value of portion control, eating frequency, meal replacements, and very-low-energy diets are discussed as well as physical activity, behavior therapy, pharmacotherapy, and surgery. Public policy changes to create environments that can assist all populations to achieve and sustain healthful lifestyle behaviors are also reviewed.

The relationship between plasma levels of Lp[a] and LDL was examined using dietary regimens. In 81 normolipidemic male outpatients, dietary cholesterol was increased by consuming six eggs per day from a mean (SD) level of 311 (162) to 1430 (198) mg per day. Mean (SD) LDL-cholesterol levels increased from 102 (26) mg/dl to 120 (33) mg/dl (P less than 0.001), while mean (SD) Lp[a] levels were 5.5 (6.1) mg/dl on the basal diet and 5.6 (6.4) mg/dl on the cholesterol-rich diet. No significant correlation was observed between increases in either LDL-cholesterol or apolipoprotein B to Lp[a], nor was there any relationship between individual baseline levels of Lp[a] and dietary-induced changes of Lp[a]. Fourteen of the 81 participants were reexamined under strict nutritional control. Four diets with 40% of calories as fat, but differing in the type of fat and the amount of cholesterol, were administered sequentially to all subjects. As expected, mean (SD) LDL-cholesterol and apolipoprotein B levels were highest on the saturated fat, high cholesterol diet (112 (32) mg/dl and 79 (22) mg/dl) and lowest on the polyunsaturated fat, low cholesterol diet (77 (27) mg/dl and 53 (18) mg/dl). In contrast, mean Lp[a] levels did not significantly change among the four diets (range 4.2-4.9 mg/dl). No correlation of Lp[a] responses with changes in plasma lipids, apolipoproteins, or lipoproteins was observed on any diet. These data suggest that determinants of plasma Lp[a] levels are distinctly different from the determinants of plasma LDL levels in normolipidemic males.

OBJECTIVES. Childhood overweight has increased significantly in the past 20 years, with the highest rates noted among Mexican Americans. Although this minority group is in significant need of intervention, few programs have demonstrated actual decreases in weight. In this study we evaluated an intensive healthy lifestyle program designed to result in weight reduction for overweight Mexican American children. We hypothesized that children randomly assigned to an intensive intervention would significantly reduce their standardized BMI when compared with children randomly assigned to a self-help condition.PATIENTS AND METHODS. A total of 60 children (33 boys; 55%) between the ages of 10 and 14 years at or above the 85th percentile for BMI were randomly assigned to a 6-month intensive-intervention or self-help condition.RESULTS. Children in the intensive-intervention condition significantly reduced their standardized BMI when compared with the children in the self-help condition. The change in standardized BMI was significantly different at both 3 and 6 months, with intensive-intervention participants showing greater decreases in weight.CONCLUSIONS. Overall, the results were promising, suggesting that an intensive, individualized intervention may be an effective means for promoting weight loss in overweight Mexican American children.

Childhood overweight has increased significantly in the past 20 years, with the highest rates noted among Mexican Americans. Schools are an optimal setting for intervention efforts; however, few programs have demonstrated actual decreases in weight. This study evaluated an intensive school-based program designed to result in weight reduction for overweight Mexican American children. A total of 71 children (32 males, 48%) between the ages of 10 and 14 at or above the 85th percentile for body mass index (BMI) were randomized into a six-month intensive intervention (II) or self-help (SH) condition. Results revealed that children in the II condition significantly reduced their standardized BMI (zBMI) when compared with the children in the self-help condition (F(2,62)=6.58, p=0.003). The change in zBMI was significantly different at both 3 and 6 months (F(1,63)=5.74, p=0.019, F(1,63)=12.61, p=0.001, respectively) with II participants showing greater decreases in weight. The 3-month change in zBMI for the II participants was a decrease of 0.07 compared with a decrease of 0.01 for SH participants. The 6-month change in zBMI was a decrease of 0.11 for II and an increase of 0.03 for SH. Overall, the results are promising, suggesting that an intensive school-based intervention may be an effective means for promoting weight loss in overweight Mexican American children.

The purpose of the present study was to determine the effect of body weight on blood lipid profile, insulin resistance and inflammatory biomarkers in Mexican-American children.Children (13.3+/-0.1 year) were recruited from a local school and assigned to one of three groups as a volunteer sample: healthy weight (HW) (or =10th and85th BMI percentile; n=42), at risk of overweight (RO) (or =85th and95th; n =25) or overweight (OW) (or =95th; n=42). Plasma concentrations of hsCRP, sCD14, sIL-6R, sTNF-alphaR1, sTNF-alphaR2, IL-6 and TNF-alpha were determined by ELISA.OW children had significantly greater plasma concentrations of hsCRP (P =0.003), sCD14 (P =0.013), sIL-6R (P =0.010), sTNF-alphaR1 (P0.001), sTNF-alphaR2 (P=0.005), insulin (P=0.001), TC:HDL ratio (P0.001) and triglycerides (P0.001) than HW children. Also plasma concentrations of hsCRP, sIL-6R and sTNF-alphaR1 were significantly greater in OW compared with RO children.Overweight Mexican-American children had a higher concentration of inflammatory biomarkers than healthy weight children. To our knowledge, this is the first study to report that sCD14 is elevated in overweight compared with healthy weight Mexican-American children.

ZVex™ and GLAAS™ are two dendritic-cell (DC) targeting platform technologies designed to enhance immune responses through the in vivo induction of antigen specific CD8 and CD4 T-cells, respectively. ZVex™ is a lentiviral vector pseudotyped with a modified Sindbis virus envelope engineered to deliver tumor antigen-encoding nucleic acids to dendritic cells in vivo. GLAAS™(Glucopyranosyl Lipid A Adjuvant System) activates DC by binding to the TLR-4 receptor and inducing strong Th1 type CD4 responses against co-delivered recombinant proteins. Currently both platform technologies are being investigated in phase I clinical trials in cancer patients. Human carbonic anhydrase 9 (hCAIX) is a tumor-associated transmembrane antigen that is over-expressed on various cancer cell types. We mapped hCAIX specific, multi-functional CD8 and CD4 T-cell epitopes within the extracellular and transmembrane regions of the protein for the mouse haplotype H-2b by intracellular cytokine staining. Mice lethally challenged s.c. on the flank with a B16-F10 tumor cell line expressing the hCAIX protein (designated BC.12) fully controlled large tumors (>100 mm2) when therapeutically immunized (subcutaneously at the base of tail) with ZVex™ encoding hCAIX or the recombinant hCAIX protein with GLAAS™ (either s.c. or i.m.). In both models, tumor control was dose-dependent. Additionally, the presence of a strong transmembrane H-2b restricted CD8 T-cell epitope was required for tumor control and regression. hCAIX-specific CD8 T-cell responses were detectable as far out as day 67 post challenge in mice displaying full regression of tumor. These results demonstrate proof of concept for ZVex™ and GLAAS™ platform technologies in an aggressive murine melanoma model. Citation Format: David J. Campbell, Rebecca S. Reeves, Patrick A. Flynn, Scott H. Robbins, Peter Berglund, Jan H. ter Meulen. Therapeutic efficacy of the ZVex™ and GLAAS™ platforms in a B16-F10/hCAIX melanoma mouse model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2505. doi:10.1158/1538-7445.AM2015-2505

Objective: Ghrelin is postulated to be an orexigenic signal that promotes weight regain after weight loss (WL). However, it is not known whether this putative effect of ghrelin is sustained after weight stabilization. The objective of this study was to investigate the relationship of plasma ghrelin concentrations to active WL and weight maintenance in obese subjects. Research Methods and Procedures: This study was a randomized clinical trial, with a 12-month follow-up period. Obese Mexican-American women matched for age and BMI were randomized to a 12-month WL program (n = 25) or no intervention (controls, n = 23). Interventions included diet, exercise, and orlistat. Body weight and fasting ghrelin, leptin, insulin, and glucose concentrations were measured at baseline and 6 and 12 months. Results: The WL group lost 8.5% of body weight after 6 months and maintained the new weight for the next 6 months. Ghrelin concentrations increased significantly at 6 months but returned to baseline at 12 months. Baseline ghrelin concentrations were directly related to the degree of WL achieved after 12 months. Controls experienced no change in BMI or ghrelin levels. There were no associations between plasma ghrelin and leptin or insulin concentrations. Discussion: Consistent with previous results, ghrelin rises in response to WL, perhaps as a counterregulatory mechanism. However, the present results indicate that ghrelin concentrations return to baseline with sustained weight maintenance, suggesting that its effects are unlikely to regulate long-term energy balance. Baseline ghrelin concentrations are related to the degree of WL that can be achieved by active weight reduction.

Objective. There is a significant need for an obesity treatment model suitable for the primary care environment. We examined the effectiveness of a brief counselling intervention alone, in combination with orlistat, and drug-alone in a 12-month randomized-clinical trial at a medical school obesity centre. Methods. Participants (N = 250) with body mass index (BMI) ≥27 were randomized. Changes in body weight, lipids, blood pressure and serum glucose were examined. Drug adherence and attendance were also evaluated. Results. Completers analysis was conducted on 136 participants with data at baseline, 6 and 12 months and intention-to-treat analyses (ITT) for the total sample. Amongst completers, participants in the drug only (P = 0.012) and drug + brief counselling (P = 0.001) groups lost more weight (mean ± SD: −3.8 ± 5.8 kg and −4.8 ± 4.4 kg, respectively) than participants in the brief counselling only group at 6 months (−1.7 ± 3.3 kg), but there were no significant group differences at 12 months. ITT model results were similar to completers at 6 months and remained significant at 12 months, but the weight losses were more modest (

This study investigated the ability of negatively versus positively perceived stress to predict outcome of treatment for binge eating disorder (BED). Participants were 62 obese women satisfying the DSMIV research criteria for BED. Stress was measured using an instrument based on the Recent Life Change Questionnaire (RLCQ). Participants experiencing high negative stress during the study period reported a binge eating frequency three times greater than that reported by subjects experiencing low negative stress (2.14 vs. 0.65 binge-days/week). Negative stress predicted how fast an individual would reduce binge eating and demonstrated more predictive power than positive stress.

Aims To investigate the effects of a pharmacotherapy (orlistat) plus lifestyle management (OLM) intervention on weight loss in Mexican American women with and without metabolic syndrome (MS). Methods: One hundred and seven female participants aged 21–65 years and of Mexican origin were randomized to either OLM or a wait-list control group (WLC) for one year. The lifestyle interventions were tailored to exhibit features of the Mexican culture. Within each group, subjects with MS were compared to those without MS to assess whether its presence mitigates weight loss. Risk factors for MS also were assessed. Results: Participants with MS in the OLM group experienced significant decreases in weight and body mass index (BMI) as compared to participants without MS. Participants with MS in the OLM group and who completed the study lost 9.3±7.5 kg (20.5±16.5 lb) as compared to participants with MS in the WLC group, who only lost 0.2±3.1 kg (0.4±6.8 lb). Further, participants with MS in the OLM group who completed the study experienced a 3.1±3.9 kg/m2 decrease in BMI whereas participants with MS in the WLC group only experienced a 0.1±1.2 kg/m2 decrease in BMI. No changes in other MS risk factors were significant. Conclusions: Patients with MS experienced significant weight loss and decreases in BMI as a result of a lifestyle and pharmacotherapy intervention.

Background Increasingly, genetic specimens are collected to expand the value of clinical trials through study of genetic effects on disease incidence, progression or response to interventions. Purpose and methods We describe the experience obtaining IRB-approved DNA consent forms across the 19 institutions in the Action for Health in Diabetes (Look AHEAD), a clinical trial examining the effect of a lifestyle intervention for weight loss on the risk of serious cardiovascular events among individuals with type 2 diabetes. We document the rates participants provided consent for DNA research, identify participant characteristics associated with consent, and discuss implications for genetics research. Results IRB approval to participate was obtained from 17 of 19 institutions. The overall rate of consent was 89.6% among the 15 institutions that had completed consenting at the time of our analysis, which was higher than reported for other types of cohort studies. Consent rates were associated with factors expected to be associated with weight loss and cardiovascular disease and to affect the distribution of candidate genes. Non-consent occurred more frequently among participants grouped as African-American, Hispanic, female, more highly educated or not dyslipidemic. Limitations The generalizabilty of results is limited by the inclusion/exclusion criteria of the trial. Conclusions Barriers to obtaining consent to participate in genetic studies may differ from other recruitment settings. Because of the potentially complex associations between personal characteristics related to adherence, outcomes and gene distributions, differential rates of consent may introduce biases in estimates of genetic relationships.