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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.

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.

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.

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.

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 (

Plasminogen activator inhibitor 1 (PAI-1) is elevated in obese individuals with type 2 diabetes and may contribute, independently of traditional factors, to increased cardiovascular disease risk. Fiber intake may decrease PAI-1 levels. We examined the associations of fiber intake and its changes with PAI-1 before and during an intensive lifestyle intervention (ILI) for weight loss in 1,701 Look AHEAD (Action for Health in Diabetes) participants with dietary, fitness, and PAI-1 data at baseline and 1 year. Look AHEAD was a randomized cardiovascular disease trial in 5,145 overweight/obese patients with type 2 diabetes, comparing ILI (goal of ≥7% reduction in baseline weight) with a control arm of diabetes support and education. ILI participants were encouraged to consume vegetables, fruits, and grain products low in sugar and fat. At baseline, median fiber intake was 17.9 g/day. Each 8.3 g/day higher fiber intake was associated with a 9.2% lower PAI-1 level ( P =0.008); this association persisted after weight and fitness adjustments ( P =0.03). Higher baseline intake of fruit ( P =0.019) and high-fiber grain and cereal ( P =0.029) were related to lower PAI-1 levels. Although successful in improving weight and physical fitness at 1 year, the ILI in Look AHEAD resulted in small increases in fiber intake (4.1 g/day, compared with –2.35 g/day with diabetes support and education) that were not related to PAI-1 change ( P =0.34). Only 31.3% of ILI participants (39.8% of women, 19.1% of men) met daily fiber intake recommendations. Increasing fiber intake in overweight/obese individuals with diabetes interested in weight loss is challenging. Future studies evaluating changes in fiber consumption during weight loss interventions are warranted.

Dietitians face both a responsibility and an opportunity to address the ethical issues of obesity treatment and to promote weight management strategies that are beneficial and effective. The Code of Ethics for the Profession of Dietetics, which was adopted in 1989 to provide guidance to dietetics practitioners in their professional practice and conduct, can serve as a guide in an evaluation of current obesity treatments. Dietitians must help clients be realistic about their weight loss goals and address emotional conflicts that may be undermining weight management efforts. Referrals to therapists may be indicated, and dietitians must be prepared to recognize the need and make the recommendations. Dietitians should take the lead in developing more ethical and beneficial treatments by collaborating with government and industry to protect the consumer from ineffective or potentially harmful practices.