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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.

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 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 .

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.

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.

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.

Obesity is a health problem of considerable magnitude. Ninety-four black obese women currently participating in a lifestyle intervention study were used to determine what relationship exists between hyperinsulinemia (determined at baseline) and change in body mass index (BMI) (at 16 weeks) controlling for the variables: baseline BMI, treatment group, and physical activity level. The subjects were divided into two groups based on baseline fasting serum insulin levels, (normoinsulinemic ⩽ 25 μU/ml and hyperinsulinemic > 25 μU/ml), and a regression analysis was used to determine what relationship exists between fasting serum insulin level and change in BMI. The regression analysis found that baseline fasting serum insulin level was not significantly related to the mean change in log of BMI (t = 0.415, p > 0.05) controlling for the variables: log of BMI at baseline, treatment group, and physical activity level. The analysis did find that the entire regression model (log of BMI at baseline, treatment group, physical activity level, and insulin level) explained 90% of the variation in the mean change in log of BMI (p

Abstinence from alcohol consumption for 3 weeks was followed by 3 weeks of wine intake in 18 inactive and 18 physically active premenopausal women (runners). The runners weighed less and had higher plasma high-density lipoprotein (HDL) cholesterol and lower low-density lipoprotein cholesterol levels than the inactive women. There were no differences between groups in plasma total cholesterol, triglyceride and apolipoprotein A-I concentrations. Runners had higher plasma HDL 2 cholesterol concentrations than inactive women (34 ± 17 vs 19 ± 12 mg/dl), but HDL 3 cholesterol concentration did not differ between the groups (41 ± 10 vs 39 ± 9 mg/dl). Addition of 35 g/day of ethanol for 3 weeks did not result in a significant change in either group for any of the variables measured. The amount of exercise appears to be a more important determinant of plasma lipoproteins and apolipoprotein A-I than alcohol intake in premenopausal women.

In this study, costs were compared for moderate- and low-cost menus recommended by the USDA and for modified menus designed to lower serum cholesterol.