Autonomous stimulation of cancer cell plasticity by the human NKG2D lymphocyte receptor coexpressed with its ligands on cancer cells.

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.

Findings from an online behavioural weight management programme provided with or without a fortified diet beverage.

The present multi-centre randomised weight-loss trial evaluated the efficacy of a low-intensity 12-week online behavioural modification programme, with or without a fortified diet beverage using a 2 × 2 factorial design. A total of 572 participants were randomised to: (1) an online basic lifestyle information (OBLI) intervention, consisting of one online informational class about tips for weight management; (2) an online behavioural weight management (OBWM) intervention, entailing 12 weekly online classes focused on weight-loss behaviour modification; (3) an OBLI intervention plus a fortified diet cola beverage (BEV) containing green tea extract (total catechin 167 mg), soluble fibre dextrin (10 g) and caffeine (100 mg) (OBLI+BEV); (4) OBWM+BEV. Assessments included height, weight, dual-energy X-ray absorptiometry-derived body composition, and waist circumference (WC). Attrition was 15·7 %. Intention-to-treat (ITT) models demonstrated a main effect for type of Internet programme, with those assigned to the OBWM condition losing significantly more weight (F= 7·174; P= 0·008) and fat mass (F= 4·491; P= 0·035) than those assigned to the OBLI condition. However, there was no significant main effect for the OBWM condition on body fat percentage (F= 2·906; P= 0·089) or WC (F= 3·351; P= 0·068), and no significant main effect for beverage use or significant interactions between factors in ITT models. A 12-week, low-intensity behaviourally based online programme produced a greater weight loss than a basic information website. The addition of a fortified diet beverage had no additional impact.

Readiness redefined: a behavioral task during screening predicted 1-year weight loss in the look AHEAD study.

OBJECTIVE: Predicting outcome in weight loss trials from baseline characteristics has proved difficult. Readiness to change is typically measured by self-report. METHODS: 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. RESULTS: 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, and <0.001, respectively, compared to <20 words per day). CONCLUSIONS: 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.

Plasma concentrations of trans fatty acids in persons with type 2 diabetes between September 2002 and April 2004.

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 (R(2) = 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 NCT00017953.

Increasing vegetable intake in Mexican-American youth: a randomized controlled trial.

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<0.001) as well as variety of vegetables eaten (F=13.69, P<0.001) when compared to those in the exposure-only condition. The findings of this study suggest that the pairing of vegetables with a preferred taste, such as peanut butter, may be an effective technique in increasing consumption, especially in children who report being resistant to eating vegetables.

Expression, signaling proficiency, and stimulatory function of the NKG2D lymphocyte receptor in human cancer cells.

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.

The use of a commercial vegetable juice as a practical means to increase vegetable intake: a randomized controlled trial.

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.

State of the evidence regarding behavior change theories and strategies in nutrition counseling to facilitate health and food behavior change.

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.

Weight loss in individuals with metabolic syndrome given DASH diet counseling when provided a low sodium vegetable juice: a randomized controlled trial.

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.

Effects of a school-based weight maintenance program for Mexican-American children: results at 2 years.

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.

Marine omega-3 fatty acid intake: associations with cardiometabolic risk and response to weight loss intervention in the Look AHEAD (Action for Health in Diabetes) study.

OBJECTIVE: To examine usual marine omega-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 (beta = -0.41, P < 0.001) and weakly with HDL (beta = 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.

The stratification of foods on the basis of overall nutritional quality: the overall nutritional quality index.

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.

Position of the American Dietetic Association: weight management.

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.

Results of an intensive school-based weight loss program with 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.

Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial.

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.