The ubiquitin ligase CRL2ZYG11 targets cyclin B1 for degradation in a conserved pathway that facilitates mitotic slippage.

The anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase is known to target the degradation of cyclin B1, which is crucial for mitotic progression in animal cells. In this study, we show that the ubiquitin ligase CRL2ZYG-11 redundantly targets the degradation of cyclin B1 in Caenorhabditis elegans and human cells. In C. elegans, both CRL2ZYG-11 and APC/C are required for proper progression through meiotic divisions. In human cells, inactivation of CRL2ZYG11A/B has minimal effects on mitotic progression when APC/C is active. However, when APC/C is inactivated or cyclin B1 is overexpressed, CRL2ZYG11A/B-mediated degradation of cyclin B1 is required for normal progression through metaphase. Mitotic cells arrested by the spindle assembly checkpoint, which inactivates APC/C, often exit mitosis in a process termed "mitotic slippage," which generates tetraploid cells and limits the effectiveness of antimitotic chemotherapy drugs. We show that ZYG11A/B subunit knockdown, or broad cullin-RING ubiquitin ligase inactivation with the small molecule MLN4924, inhibits mitotic slippage in human cells, suggesting the potential for antimitotic combination therapy.

Private prayer associations with depression, anxiety and other health conditions: an analytical review of clinical studies.

OBJECTIVES: To critically analyze appropriate clinical studies to assess the relationship between health conditions and the frequency of private prayer. Private prayer is defined as individuals praying for themselves. METHODS: Using PubMed and other search engines, we identified over 300 articles reporting relationships between prayer and health conditions. We identified 41 observational clinical studies that evaluated the relationship between private prayer and health conditions. Prayer scores of 5 to 1 were assigned to studies, with 5 being private prayer for health and 1 being prayer in combination with meditation or Bible study. Frequency scores ranged from 3 to 1 with 3 being twice daily or more and 0 when frequency was not assessed. Studies were ranked from 8 to 1 based on the sum of Prayer and Frequency Scores. RESULTS: Twenty-one studies had Prayer-Frequency scores of 5 to 8, indicating that they evaluated private prayer (praying for one's own health) of suitable frequency in association with health conditions. Nine of 11 studies indicated that private prayer was associated with a significantly lower prevalence of depression (P value, <0.01). Optimism as well as coping were significantly improved by prayer in four studies (P value, P < 0.01). In 10 studies of mental health conditions-including anxiety and confusion-there was a significant benefit associated with prayer (P < 0.01), In the reviewed studies, prayer did not have a significant effect on physical health or blood pressure. CONCLUSION: The reported observational studies suggest that frequent private prayer is associated with a significant benefit for depression, optimism, coping, and other mental health conditions such as anxiety. Controlled clinical trials are required to critically assess the associations of private prayer and health conditions.

Breast-feeding and cognitive development: a meta-analysis

Although the results of many clinical studies suggest that breast-fed children score higher on tests of cognitive function than do formula-fed children, some investigators have suggested that these differences are related to confounding covariables such as socioeconomic status or maternal education...

Raisins compared with other snack effects on glycemia and blood pressure: a randomized, controlled trial.

OBJECTIVE: To compare effects of raisin snacks with conventional snacks on glycemia and cardiovascular risk factors. MATERIALS AND METHODS: A 12-week, randomized, controlled trial compared 3-times-a-day consumption of raisins with intake of processed snacks on glycemia and cardiovascular risk factors. Men and women were randomized to snacks (n = 15) or raisins (n = 31). Outcome measures were performed at baseline, 4, 8, and 12 weeks. RESULTS: Fasting plasma glucose levels were not significantly affected by intake of raisins or snacks. Mean subject post prandial glucose levels were significantly reduced by raisin intake at 12 weeks; changes with raisin intake were -13.1 mg/dL (P = 0.003 vs baseline; P = 0.03 vs snacks). Eating raisins significantly decreased glycated hemoglobin (HbA1c) level (-0.12%; P = 0.004), a significantly greater level decrease than seen with snack intake (P = 0.036). Snack intake did not significantly affect subject systolic or diastolic blood pressure (BP). Raisin intake was associated with reductions in systolic blood pressure (SBP) at 4, 8, and 12 weeks with mean changes of -6.0 to 10.2 mmHg; all these changes were statistically significant (P = 0.015 to 0.001). Raisins were associated with significantly greater changes in diastolic blood pressure (DBP) at 4, 8, and 12 weeks than snacks (P < 0.05). Body weight did not significantly change within or between groups. CONCLUSIONS: Regular consumption of raisins may reduce glycemia and cardiovascular risk factors, including BP rate.

High resolution (3 Tesla) MRI-guided conformal brachytherapy for cervical cancer: consequences of different high-risk CTV sizes.

PURPOSE: To evaluate conventional brachytherapy (BT) plans using dose-volume parameters and high resolution (3 Tesla) MRI datasets, and to quantify dosimetric benefits and limitations when MRI-guided, conformal BT (MRIG-CBT) plans are generated. MATERIAL AND METHODS: Fifty-five clinical high-dose-rate BT plans from 14 cervical cancer patients were retrospectively studied. All conventional plans were created using MRI with titanium tandem-and-ovoid applicator (T&O) for delivery. For each conventional plan, a MRIG-CBT plan was retrospectively generated using hybrid inverse optimization. Three categories of high risk (HR)-CTV were considered based on volume: non-bulky (< 20 cc), low-bulky (> 20 cc and < 40 cc) and bulky (≥ 40 cc). Dose-volume metrics of D90 of HR-CTV and D2cc and D0.1cc of rectum, bladder, and sigmoid colon were analyzed. RESULTS: Tumor coverage (HR-CTV D90) of the conventional plans was considerably affected by the HR-CTV size. Sixteen percent of the plans covered HR-CTV D90 with the prescription dose within 5%. At least one OAR had D2cc values over the GEC-ESTRO recommended limits in 52.7% of the conventional plans. MRIG-CBT plans showed improved target coverage for HR-CTV D90 of 98 and 97% of the prescribed dose for non-bulky and low-bulky tumors, respectively. No MRIG-CBT plans surpassed the D2cc limits of any OAR. Only small improvements (D90 of 80%) were found for large targets (> 40 cc) when using T&O applicator approach. CONCLUSIONS: MRIG-CBT plans displayed considerable improvement for tumor coverage and OAR sparing over conventional treatment. When the HR-CTV volume exceeded 40 cc, its improvements were diminished when using a conventional intracavitary applicator.

Raisin consumption by humans: effects on glycemia and insulinemia and cardiovascular risk factors.

Raisins are widely recommended as good foods and preferred snacks because of their nutrient content. They are rich in dietary fiber, potassium, and many health-promoting phytonutrients and antioxidants. Raisins have a high dietary fiber score. Laboratory studies document that raisins rank in the upper quartile of foods for antioxidant content. Clinical research related to the potential health benefits of raisins has intensified over the past 10 y. Much of this research has focused on blood glucose and insulin responses to raisins compared to other foods or snacks. Meal studies indicate that raisins have a low to moderate glycemic index and a low insulinemic index. Longer term studies suggest that customary intake of raisins is associated with lower postprandial blood glucose values than with equicaloric control foods. Cross-sectional studies suggest that higher levels of dried fruit consumption are associated with lower systolic and diastolic blood pressure than seen with minimal dried fruit use. One clinical study documents that raisin intake over 12 wk is accompanied by a significant reduction in blood pressure. Preliminary results indicate that raisins are associated with increased satiety and decreased food consumption over an 8-h period, but the potential benefits of raisins for weight loss have not been assessed. Raisin intake is accompanied by reductions in serum low-density lipoprotein cholesterol, triglycerides, and oxidized low-density cholesterol values. Thus, raisins have the potential to significantly reduce the risk for developing diabetes or cardiovascular disease.

Quantifying variances in comparative RNA secondary structure prediction.

BACKGROUND: With the advancement of next-generation sequencing and transcriptomics technologies, regulatory effects involving RNA, in particular RNA structural changes are being detected. These results often rely on RNA secondary structure predictions. However, current approaches to RNA secondary structure modelling produce predictions with a high variance in predictive accuracy, and we have little quantifiable knowledge about the reasons for these variances. RESULTS: In this paper we explore a number of factors which can contribute to poor RNA secondary structure prediction quality. We establish a quantified relationship between alignment quality and loss of accuracy. Furthermore, we define two new measures to quantify uncertainty in alignment-based structure predictions. One of the measures improves on the "reliability score" reported by PPfold, and considers alignment uncertainty as well as base-pair probabilities. The other measure considers the information entropy for SCFGs over a space of input alignments. CONCLUSIONS: Our predictive accuracy improves on the PPfold reliability score. We can successfully characterize many of the underlying reasons for and variances in poor prediction. However, there is still variability unaccounted for, which we therefore suggest comes from the RNA secondary structure predictive model itself.

Oxfold: kinetic folding of RNA using stochastic context-free grammars and evolutionary information.

MOTIVATION: Many computational methods for RNA secondary structure prediction, and, in particular, for the prediction of a consensus structure of an alignment of RNA sequences, have been developed. Most methods, however, ignore biophysical factors, such as the kinetics of RNA folding; no current implementation considers both evolutionary information and folding kinetics, thus losing information that, when considered, might lead to better predictions. RESULTS: We present an iterative algorithm, Oxfold, in the framework of stochastic context-free grammars, that emulates the kinetics of RNA folding in a simplified way, in combination with a molecular evolution model. This method improves considerably on existing grammatical models that do not consider folding kinetics. Additionally, the model compares favourably to non-kinetic thermodynamic models.

Characterising RNA secondary structure space using information entropy.

Comparative methods for RNA secondary structure prediction use evolutionary information from RNA alignments to increase prediction accuracy. The model is often described in terms of stochastic context-free grammars (SCFGs), which generate a probability distribution over secondary structures. It is, however, unclear how this probability distribution changes as a function of the input alignment. As prediction programs typically only return a single secondary structure, better characterisation of the underlying probability space of RNA secondary structures is of great interest. In this work, we show how to efficiently compute the information entropy of the probability distribution over RNA secondary structures produced for RNA alignments by a phylo-SCFG, and implement it for the PPfold model. We also discuss interpretations and applications of this quantity, including how it can clarify reasons for low prediction reliability scores. PPfold and its source code are available from http://birc.au.dk/software/ppfold/.

StatAlign 2.0: combining statistical alignment with RNA secondary structure prediction.

MOTIVATION: Comparative modeling of RNA is known to be important for making accurate secondary structure predictions. RNA structure prediction tools such as PPfold or RNAalifold use an aligned set of sequences in predictions. Obtaining a multiple alignment from a set of sequences is quite a challenging problem itself, and the quality of the alignment can affect the quality of a prediction. By implementing RNA secondary structure prediction in a statistical alignment framework, and predicting structures from multiple alignment samples instead of a single fixed alignment, it may be possible to improve predictions. RESULTS: We have extended the program StatAlign to make use of RNA-specific features, which include RNA secondary structure prediction from multiple alignments using either a thermodynamic approach (RNAalifold) or a Stochastic Context-Free Grammars (SCFGs) approach (PPfold). We also provide the user with scores relating to the quality of a secondary structure prediction, such as information entropy values for the combined space of secondary structures and sampled alignments, and a reliability score that predicts the expected number of correctly predicted base pairs. Finally, we have created RNA secondary structure visualization plugins and automated the process of setting up Markov Chain Monte Carlo runs for RNA alignments in StatAlign. AVAILABILITY AND IMPLEMENTATION: The software is available from http://statalign.github.com/statalign/.

Frnakenstein: multiple target inverse RNA folding.

BACKGROUND: RNA secondary structure prediction, or folding, is a classic problem in bioinformatics: given a sequence of nucleotides, the aim is to predict the base pairs formed in its three dimensional conformation. The inverse problem of designing a sequence folding into a particular target structure has only more recently received notable interest. With a growing appreciation and understanding of the functional and structural properties of RNA motifs, and a growing interest in utilising biomolecules in nano-scale designs, the interest in the inverse RNA folding problem is bound to increase. However, whereas the RNA folding problem from an algorithmic viewpoint has an elegant and efficient solution, the inverse RNA folding problem appears to be hard. RESULTS: In this paper we present a genetic algorithm approach to solve the inverse folding problem. The main aims of the development was to address the hitherto mostly ignored extension of solving the inverse folding problem, the multi-target inverse folding problem, while simultaneously designing a method with superior performance when measured on the quality of designed sequences. The genetic algorithm has been implemented as a Python program called Frnakenstein. It was benchmarked against four existing methods and several data sets totalling 769 real and predicted single structure targets, and on 292 two structure targets. It performed as well as or better at finding sequences which folded in silico into the target structure than all existing methods, without the heavy bias towards CG base pairs that was observed for all other top performing methods. On the two structure targets it also performed well, generating a perfect design for about 80% of the targets. CONCLUSIONS: Our method illustrates that successful designs for the inverse RNA folding problem does not necessarily have to rely on heavy biases in base pair and unpaired base distributions. The design problem seems to become more difficult on larger structures when the target structures are real structures, while no deterioration was observed for predicted structures. Design for two structure targets is considerably more difficult, but far from impossible, demonstrating the feasibility of automated design of artificial riboswitches. The Python implementation is available at http://www.stats.ox.ac.uk/research/genome/software/frnakenstein.

Effect of a behavioral/nutritional intervention program on weight loss in obese adults: a randomized controlled trial.

BACKGROUND: Health professionals are in need of more information about the weight-loss outcomes of using commercial weight-loss programs. OBJECTIVE: A commercial behavioral intervention program using meal replacements, fruits, and vegetables (MR-FV) was compared with usual-care weight-loss counseling. DESIGN: Obese volunteers were randomly allocated to usual-care weight-loss counseling or participation in an MR-FV standardized behavioral education program. The MR-FV group attended weekly weight-loss classes for 16 weeks and weekly maintenance classes for 8 weeks. PARTICIPANTS/SETTING: Obese women or men aged 20 to 65 years were recruited from the community through a commercial program provided at a university medical center. INTERVENTION: The control group (C group) received weight-management counseling from an experienced dietitian, while the intervention group (MR-FV group) participated in scheduled behavioral weight-loss classes. The MR-FV group participants were encouraged to consume 3 shakes, 2 entrées, and 5 servings of fruits or vegetables daily, and achieve physical activity goals (expend ≥ 8.4 mJ/week); they kept records and placed midweek phone calls. The C group was counseled at baseline, 8 weeks, and 16 weeks. OUTCOME MEASURES: Both groups were seen at baseline, and 8, 16, and 24 weeks for assessment of weight, risk factors, and side effects. STATISTICAL ANALYSIS: The primary data analysis was intention to treat. RESULTS: Thirteen of 16 subjects (81.3%) in the C group and 18 of 22 subjects (81.8%) in the MR-FV group completed the 24-week study. Mean weight losses for the C group were: 1.3% (standard error [SE], 0.9) at 8 weeks; 0.7% (SE, 1.1) at 16 weeks; and 0.7% (SE, 1.1) or 0.7 kg at 24 weeks. Mean weight losses for the MR-FV group were: 8.5% (SE, 0.6) at 8 weeks, 12.5% (SE, 0.9) at 16 weeks, and 13.9% (SE, 1.1) or 13.7 kg at 24 weeks. CONCLUSIONS: A behavioral intervention with a low-energy diet including 5 meal replacements and 5 servings of fruits or vegetables enabled obese individuals to lose 13 kg more than control subjects over a 24-week period.

Reduced viscosity Barley ß-Glucan versus placebo: a randomized controlled trial of the effects on insulin sensitivity for individuals at risk for diabetes mellitus.

BACKGROUND: Prior studies suggest soluble fibers may favorably affect glucose/insulin metabolism. METHODS: This prospective, randomized, placebo controlled, double blind, parallel group trial evaluated 50 generally healthy subjects without prior diagnosis of diabetes mellitus (44 completers), who were administered beverages containing placebo (control), lower dose (3 g/d), or higher dose (6 g/d) reduced viscosity barley ß-glucan (BBG) extract. Subjects (68% women) mean age 56 years, Body Mass Index (BMI) 32 kg/m2 and baseline fasting plasma glucose 102 mg/dl were instructed to follow a weight-maintaining Therapeutic Lifestyle Changes (TLC) diet and consumed three 11 oz study beverages daily with meals for 12 weeks. The four primary study endpoint measures were plasma glucose and insulin [each fasting and post-Oral Glucose Tolerance Testing (OGTT)]. RESULTS: Compared to placebo, administration of 3 g/d BBG over 12 weeks significantly reduced glucose incremental Area Under the Curve (iAUC) measures during OGTT and 6 g/d BBG over 12 weeks significantly reduced fasting insulin as well as the related homeostasis model assessment of insulin resistance (HOMA-IR). Beverages were generally well tolerated with no serious adverse experiences and no significant differences between groups for adverse experiences. Per protocol instruction, subjects maintained body weight. CONCLUSIONS: These findings suggest 6 g/d BBG consumed in a beverage over 12 weeks may improve insulin sensitivity among hyperglycemic individuals with no prior diagnosis of diabetes mellitus, and who experience no change in body weight. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01375803.

Soy protein effects on serum lipoproteins: a quality assessment and meta-analysis of randomized, controlled studies.

OBJECTIVES: Many randomized controlled trials (RCTs) have assessed the effects of soy protein on serum lipoprotein risk factors for coronary heart disease (CHD). This review and meta-analysis assessed the quality of these RCTs and estimated the effects of soy protein consumption on serum lipoproteins. DATA SOURCES: A comprehensive search using multiple databases was conducted for the years 1996 through 2008 to identify clinical trials related to soy protein intake and serum lipoprotein changes. STUDY ELIGIBILITY: RCTs were assessed that met these requirements: soy protein intake compared with nonsoy protein, provided information on serum low-density lipoprotein (LDL)-cholesterol values, provided no more than 65 g of soy protein daily, and obtained LDL-cholesterol measurements between 4 and 18 weeks of treatment. Randomized parallel and crossover studies were evaluated. METHODS: Studies were graded for quality using 12 criteria with a possible maximum grade of 24. Net changes in lipoproteins with soy protein consumption compared with nonsoy control diets were analyzed by meta-analyses and funnel plots. Confidence intervals were constructed using inverse weighting. Analyses compared parallel to crossover studies and studies with lower and higher grades. RESULTS: Analyses included 20 parallel-design studies and 23 crossover studies. Parallel studies scored significantly higher (p < 0.001) in study quality, with a mean grade of 15.8 (95% confidence interval [CI], 14.3 to 17.3) compared with 10.1 (95% CI, 8.2 to 11.9) for crossover trials. Soy protein intake was associated with net changes in serum LDL-cholesterol values of -0.23 mmol/l (95% CI, -0.28 to -0.18 mmol/l) or a 5.5% reduction in parallel studies and -0.16 mmol/l (95% CI, -0.22 to -0.11 mmol/l) or a reduction of 4.2% with crossover studies (p < 0.001 for parallel vs crossover). In parallel studies, net serum HDL-cholesterol values were 3.2% higher (p < 0.007) with soy vs control, and fasting serum triacylglycerol values were 10.7% lower (p < 0.008) for soy vs control. CONCLUSIONS AND IMPLICATIONS: Soy protein consumption with a median of 30 g/d was associated with a significant improvement in lipoprotein risk factors for CHD. Compared with crossover RCTs, parallel RCTs had significantly higher quality grades and were associated with significantly greater improvements in serum LDL-cholesterol values. Regular consumption of 1 to 2 servings of soy protein daily (15 to 30 g) has a significant favorable impact on serum lipoprotein risk factors for CHD.

Reductions in medications with substantial weight loss with behavioral intervention.

Medical costs of obesity in the United States exceed $147 billion annually with medication costs making a sizable contribution. We examined medication costs associated with substantial weight losses in an intensive behavioral weight loss program. Inclusion criteria were medication use for obesity co-morbidities: hypertension, diabetes, dyslipidemia, degenerative joint disease, or gastroesophageal reflux disease. Group A, 83 obese patients on medications completed 8 weeks of classes, lost 19 kg in 20 weeks. Group B, 100 severely obese patients, lost 59 kg in 45 weeks. Medications were discontinued: Group A, 18%; Group B, 64%. Mean numbers of medications decreased significantly for all co-morbidities. Mean numbers of daily medications, initial and final, respectively were: Group A, total, 3.0 ± 0.2 (mean ± SEM) and 1.7 ± 0.2; Group B, total, 2.5 ± 0.2 and 0.7 ± 0.1. Monthly costs for all medications decreased significantly for all co-morbidities and were as follows: Group A, total, $249 ± 25 and $153 ± 19; Group B: total, $237 ± 27 and $65 ± 12. Medically supervised weight loss is very effective approach for improving cardiovascular risk factors and reducing medical costs.

Sequential changes of serum aminotransferase levels in severely obese patients after losing weight through enrollment in a behavioral weight loss program.

Nonalcoholic fatty liver disease (NAFLD) is very prevalent in obese patients. However, increases in serum aminotransferase levels after weight loss have raised clinical concerns. This study documented sequential changes of serum aminotransferase levels for severely obese patients who lost a substantial amount of weight in a behavioral weight loss program. One hundred three severely obese patients who lost > 45.5 kg were treated in our clinic's weight management program. The prevalence of all risk factors except diabetes was higher among those with elevated (AE) baseline serum alanine transferase (ALT) levels than those with normal levels (AN). Weight losses at 8 and 24 weeks were 19.8 and 43.5 kg in the AN group (n = 79 patients) and 21.8 and 45.5 kg in the AE group (n = 24 patients), respectively. Total weight losses after completion of the program were 58.4 kg in the AN group and 57.6 kg in the AE group. The baseline levels for the AN group were: ALT, 25.4 U/L and aspartate aminotransferase (AST)/ALT ratio, 0.87. The baseline levels for the AE group were: ALT, 68.0 U/L and AST/ALT ratio, 0.61. Peak ALT levels were 75.4 U/L in the AN group and 94.0 U/L in the AE group. The final serum ALT levels were 23.7 U/L and 27.3 U/L in the AN and AE groups, respectively. This severely obese population had a very high frequency of ALT elevations with weight loss, but elevations were transient; values usually returned to below baseline levels after substantial weight loss.

Functional foods for dyslipidaemia and cardiovascular risk prevention.

A food can be regarded as 'functional' if it can demonstrate a beneficial efficacy on one or more target functions in the body in a convincing way. Beyond adequate nutritional qualities, functional foods should either improve the state of health and wellbeing and/or reduce the risk of disease. Functional foods that are marketed with claims of heart disease reduction focus primarily on the major risk factors, i.e. cholesterol, diabetes and hypertension. Some of the most innovative products are designed to be enriched with 'protective' ingredients, believed to reduce risk. They may contain, for example, soluble fibre (from oat and psyllium), useful both for lowering cholesterol and blood pressure, or fructans, effective in diabetes. Phytosterols and stanols lower LDL-cholesterol in a dose-dependent manner. Soya protein is more hypocholesterolaemic in subjects with very high initial cholesterol and recent data indicate also favourable activities in the metabolic syndrome. n-3 Fatty acids appear to exert significant hypotriacylglycerolaemic effects, possibly partly responsible for their preventive activity. Dark chocolate is gaining much attention for its multifunctional activities, useful both for the prevention of dyslipidaemia as well as hypertension. Finally, consensus opinions about tea and coffee have not emerged yet, and the benefits of vitamin E, garlic, fenugreek and policosanols in the management of dyslipidaemia and prevention of arterial disease are still controversial.

Effects of meals high in carbohydrate, protein, and fat on ghrelin and peptide YY secretion in prepubertal children.

CONTEXT: Ghrelin and peptide YY (PYY) are two hormones produced by the gastrointestinal tract that have effects on appetite. However, little is known about their secretion in response to meals high in individual macronutrients in prepubertal children. OBJECTIVE: We sought to understand how meals high in carbohydrate, protein, and fat affect serum concentrations of total ghrelin and total PYY, hypothesizing that these macronutrients would exert differential effects on their secretion. DESIGN AND SETTING: This was a cross-sectional study at one tertiary care center. SUBJECTS: Subjects were 7- to 11-yr-old healthy normal-weight (NW) and obese (OB) volunteers recruited from local advertisements. INTERVENTIONS: After an overnight fast, the subjects were given a breakfast high in carbohydrate, protein, or fat at 0800 h. Blood samples for total ghrelin and total PYY were taken at baseline, 30 min, and hourly from 0900 to 1200 h. MAIN OUTCOME MEASURE: We assessed postprandial ghrelin suppression and PYY elevation, as well as changes in reported hunger and satiety, after the three test meals. RESULTS: After the high-protein meal, ghrelin declined gradually in both groups over the study period without subsequent increase, whereas ghrelin suppressed more rapidly to a nadir at 60 min after the high-carbohydrate meal in both NW and OB children, followed by rebound in ghrelin levels. Similarly, after the high-protein meal, PYY concentrations increased steadily over the course of the morning in both groups without decline, whereas PYY levels peaked 30 min after the high-carbohydrate meal in both NW and OB subjects with significant decline thereafter. Ghrelin and PYY responses to the high-fat meal were somewhat intermediate between that observed with high carbohydrate and high protein. The OB children reported higher hunger and lower satiety after the high-carbohydrate meal compared to the NW subjects, whereas appetite ratings were similar between the groups after the high-protein and high-fat meals. Additionally, within the OB group, area under the curve (AUC) analysis revealed significantly greater PYY response, as well as lower AUC hunger and higher AUC satiety, to the high-protein meal than the high-carbohydrate and high-fat meals. CONCLUSIONS: The patterns of secretion of ghrelin and PYY in our study of prepubertal children suggest that they may play a role in the effectiveness of high-protein/low-carbohydrate diets in promoting weight loss.

Glucagon-like peptide 1 and pancreatic polypeptide responses to feeding in normal weight and overweight children.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) and pancreatic polypeptide (PP) are intestinal hormones that are involved in the post-prandial satiety response. We sought to assess meal-related changes in these hormones in young children and determine whether differences exist between normal weight (NW) and overweight (OW) children. METHODS: Seven to 11-year-old healthy NW (n=20) and OW (n=12) volunteers were given a standardized breakfast and lunch following an overnight fast and had measurements of GLP-1 and PP over 9 hours. We characterized whether GLP-1 and PP changed from the pre-prandial to the post-prandial state and whether the serum levels corresponded to reported appetite. RESULTS: GLP-1 did not increase after eating, did not decline prior to the next meal, and did not correspond to satiety ratings in either group. PP increased post-prandially in OW children after both breakfast and lunch, but in the NW group PP only increased after breakfast. PP levels did not decline in either group as the next meal approached. CONCLUSIONS: In our study of school-age children, feeding had little effect on GLP-1 secretion and a variable effect on serum PP levels. Observed differences in the GLP-1 and PP responses between the NW and OW groups do not suggest there is an intrinsic abnormality in their secretion that causes weight gain.

A systematic review of targeted outcomes associated with a medically supervised commercial weight-loss program.

Accurate information about weight loss is not available for most commercial weight-loss programs. Our objective was to obtain accurate assessments of weight outcomes, behavioral data, and side effects for an intensive behavioral weight-loss program using low-energy diets. Weights, behavioral data, and side effects for 173 consecutive patients were assessed. Treatment options were Medically Supervised, using a minimum of five meal replacements per day, and Healthy Solutions, using meal replacements, fruits, and vegetables. Both options included weekly classes, daily records, midweek phone calls, and a minimum physical activity goal of 2,000 kcal/week. The primary outcome was change in body weight with secondary outcomes related to behavioral changes and side effects. Intention-to-treat (ITT) and completer analyses (completed 9 weeks of treatment) were performed. During 13 months, 173 patients met criteria for analysis. They selected either Healthy Solutions: 56 patients (ITT) and 37 completers; or Medically Supervised: 117 patients (ITT) and 93 completers. Mean (+/-standard error) weight losses were: Healthy Solutions: ITT=12.8+/-1.3 kg in 13 weeks and completers=17.0+/-1.4 kg in 18 weeks; Medically Supervised: ITT=16.6+/-1.0 kg in 16 weeks and completers=19.7+/-1.0 kg in 19 weeks. Mean use of meal replacements, fruits, and vegetables exceeded goals. Most side effects were mild and did not affect program continuation. An intensive behavioral weight-loss program using low-energy diets, including five meal replacements daily, is safe and effective.