Exercise and diet-induced weight loss attenuates oxidative stress related-coronary vasoconstriction in obese adolescents.

Obesity is a disease of oxidative stress (OS). Acute hyperoxia (breathing 100 % O(2)) can evoke coronary vasoconstriction by the oxidative quenching of nitric oxide (NO). To examine if weight loss would alter the hyperoxia-related coronary constriction seen in obese adolescents, we measured the coronary blood flow velocity (CBV) response to hyperoxia using transthoracic Doppler echocardiography before and after a 4-week diet and exercise regimen in 6 obese male adolescents (age 13-17 years, BMI 36.5 ± 2.3 kg/m(2)). Six controls of similar age and BMI were also studied. The intervention group lost 9 ± 1 % body weight, which was associated with a reduced resting heart rate (HR), reduced diastolic blood pressure (BP), and reduced RPP (all P < 0.05). Before weight loss, hyperoxia reduced CBV by 33 ± 3 %. After weight loss, CBV only fell by 15 ± 3 % (P < 0.05). In the control group, CBV responses to hyperoxia were unchanged during the two trials. Thus weight loss: (1) reduces HR, BP, and RPP; and (2) attenuates the OS-related coronary constrictor response seen in obese adolescents. We postulate that: (1) the high RPP before weight loss led to higher myocardial O(2) consumption, higher coronary flow and greater NO production, and in turn a large constrictor response to hyperoxia; and (2) weight loss decreased myocardial oxygen demand and NO levels. Under these circumstances, hyperoxia-induced vasoconstriction was attenuated.

Superior mesenteric artery syndrome in intellectually disabled children.

OBJECTIVES: Superior mesenteric artery syndrome (SMAS) is a rare cause of small intestinal obstruction in pediatric patients. Children with intellectual disabilities are a challenging patient population in which to make this diagnosis. The goal of this study was to determine the frequency, presenting symptoms, and outcomes of SMAS in intellectually disabled and non-intellectually disabled children. METHODS: Retrospective chart review of pediatric patients with SMAS admitted to Penn State Hershey Children's Hospital between January 1999 and July 2010. RESULTS: Sixteen children with SMAS were identified. The majority were male (n = 9) and more than two thirds had an intellectual disability (n = 11). Presenting symptoms were similar between groups, but 78% (7/9) of intellectually disabled patients who had a gastrostomy tube presented with feeding intolerance. Although intellectually disabled patients had a higher number of comorbidities and the number of health care visits before diagnosis was higher, this did not reach statistical significance. There were also no significant differences in length of symptoms before diagnosis and amount of weight loss. However, the weight-for-age percentiles in intellectual disabled children were significantly lower in those without an intellectual disability (9.09 [20.31] vs 48 [20.19], respectively, P ≤ 0.001). Seventy-five percent of patients responded favorably to conservative treatment, but 36% (4/11) of intellectually disabled patients required multiple treatments before there was an improvement in their condition. CONCLUSIONS: Superior mesenteric artery syndrome was found more often in children with an intellectual disability. These data highlight the need to consider SMAS if there is difficulty tolerating gastrostomy tube feedings in patients with weight-for-age percentiles less than 5%.

Partial order optimum likelihood (POOL): maximum likelihood prediction of protein active site residues using 3D Structure and sequence properties.

A new monotonicity-constrained maximum likelihood approach, called Partial Order Optimum Likelihood (POOL), is presented and applied to the problem of functional site prediction in protein 3D structures, an important current challenge in genomics. The input consists of electrostatic and geometric properties derived from the 3D structure of the query protein alone. Sequence-based conservation information, where available, may also be incorporated. Electrostatics features from THEMATICS are combined with multidimensional isotonic regression to form maximum likelihood estimates of probabilities that specific residues belong to an active site. This allows likelihood ranking of all ionizable residues in a given protein based on THEMATICS features. The corresponding ROC curves and statistical significance tests demonstrate that this method outperforms prior THEMATICS-based methods, which in turn have been shown previously to outperform other 3D-structure-based methods for identifying active site residues. Then it is shown that the addition of one simple geometric property, the size rank of the cleft in which a given residue is contained, yields improved performance. Extension of the method to include predictions of non-ionizable residues is achieved through the introduction of environment variables. This extension results in even better performance than THEMATICS alone and constitutes to date the best functional site predictor based on 3D structure only, achieving nearly the same level of performance as methods that use both 3D structure and sequence alignment data. Finally, the method also easily incorporates such sequence alignment data, and when this information is included, the resulting method is shown to outperform the best current methods using any combination of sequence alignments and 3D structures. Included is an analysis demonstrating that when THEMATICS features, cleft size rank, and alignment-based conservation scores are used individually or in combination THEMATICS features represent the single most important component of such classifiers.

Associations between obesity severity and medical comorbidities for children with obesity in low intensity hospital intervention.

BACKGROUND: Childhood obesity has increased dramatically in the United States. Most available research has followed obesity prevalence with little attention to medical comorbidities, which could guide prevention and intervention. METHODS: A retrospective chart review examined 2038 children referred to a Pediatric Weight Management Clinic providing low intensity (<26 contact hours) intervention. Linear regression examined associations between obesity severity level (I, II, III) and blood pressure percentile scores (systolic, diastolic) while controlling for gender, age group, and ethnicity. Logistical regression examined associations between obesity severity level and five medical diagnoses (hypertension, type 2 diabetes, elevated ALT, hyperlipidemia, obstructive sleep apnea), again controlling for demographics. RESULTS: Results revealed that children with Class III obesity severity had significantly greater risk for five of the seven medical conditions examined, with higher systolic and diastolic blood pressure scores, and higher odds for hypertension, type 2 diabetes, and obstructive sleep apnea. CONCLUSION: The US Preventive Services Task Force has documented the effectiveness of intensive behavioral interventions (>26 contact hours for changes in diet, exercise, screen time) for reducing obesity severity in children. Additional research is required to determine whether more intensive behavioral approaches should be added before a child's obesity reaches the Class III level of severity in order to prevent medical comorbidities.

Enhanced performance in prediction of protein active sites with THEMATICS and support vector machines.

Theoretical microscopic titration curves (THEMATICS) is a computational method for the identification of active sites in proteins through deviations in computed titration behavior of ionizable residues. While the sensitivity to catalytic sites is high, the previously reported sensitivity to catalytic residues was not as high, about 50%. Here THEMATICS is combined with support vector machines (SVM) to improve sensitivity for catalytic residue prediction from protein 3D structure alone. For a test set of 64 proteins taken from the Catalytic Site Atlas (CSA), the average recall rate for annotated catalytic residues is 61%; good precision is maintained selecting only 4% of all residues. The average false positive rate, using the CSA annotations is only 3.2%, far lower than other 3D-structure-based methods. THEMATICS-SVM returns higher precision, lower false positive rate, and better overall performance, compared with other 3D-structure-based methods. Comparison is also made with the latest machine learning methods that are based on both sequence alignments and 3D structures. For annotated sets of well-characterized enzymes, THEMATICS-SVM performance compares very favorably with methods that utilize sequence homology. However, since THEMATICS depends only on the 3D structure of the query protein, no decline in performance is expected when applied to novel folds, proteins with few sequence homologues, or even orphan sequences. An extension of the method to predict non-ionizable catalytic residues is also presented. THEMATICS-SVM predicts a local network of ionizable residues with strong interactions between protonation events; this appears to be a special feature of enzyme active sites.

American Society of Clinical Oncology Summit on Addressing Obesity Through Multidisciplinary Provider Collaboration: Key Findings and Recommendations for Action.

OBJECTIVE: Given the increasing evidence that obesity increases the risk of developing and dying from malignancy, the American Society of Clinical Oncology (ASCO) launched an Obesity Initiative in 2013 that was designed to increase awareness among oncology providers and the general public of the relationship between obesity and cancer and to promote research in this area. Recognizing that the type of societal change required to impact the obesity epidemic will require a broad-based effort, ASCO hosted the "Summit on Addressing Obesity through Multidisciplinary Collaboration" in 2016. METHODS: This meeting was held to review current challenges in addressing obesity within the respective health care provider communities and to identify priorities that would most benefit from a collective and cross-disciplinary approach. RESULTS: Efforts focused on four key areas: provider education and training; public education and activation; research; and policy and advocacy. Summit attendees discussed current challenges in addressing obesity within their provider communities and identified priorities that would most benefit from multidisciplinary collaboration. CONCLUSIONS: A synopsis of recommendations to facilitate future collaboration, as well as examples of ongoing cooperative efforts, provides a blueprint for multidisciplinary provider collaboration focused on obesity prevention and treatment.

Statistical criteria for the identification of protein active sites using Theoretical Microscopic Titration Curves.

Theoretical Microscopic Titration Curves (THEMATICS) may be used to identify chemically important residues in active sites of enzymes by characteristic deviations from the normal, sigmoidal Henderson-Hasselbalch titration behavior. Clusters of such deviant residues in physical proximity constitute reliable predictors of the location of the active site. Originally the residues with deviant predicted behavior were identified by human observation of the computed titration curves. However, it is preferable to select the unusual residues by mathematically well-defined criteria, in order to reduce the chance of error, eliminate any possible biases, and substantially speed up the selection process. Here we present some simple statistical tests that constitute such selection criteria. The first derivatives of the predicted titration curves resemble distribution functions and are normalized. The moments of these first derivative functions are computed. It is shown that the third and fourth moments, measures of asymmetry and kurtosis, respectively, are good measures of the deviations from normal behavior. Results are presented for 44 different enzymes. Detailed results are given for 4 enzymes with 4 different types of chemistry: arginine kinase from Limulus polyphemus (horseshoe crab); beta-lactamase from Escherichia coli; glutamate racemase from Aquifex pyrophilus; and 3-isopropylmalate dehydrogenase from Thiobacillus ferrooxidans. The relationship between the statistical measures of nonsigmoidal behavior in the predicted titration curves and the catalytic activity of the residue is discussed.

Pediatric obesity and depression: a cross-sectional analysis of absolute BMI as it relates to children's depression index scores in obese 7- to 17-year-old children.

UNLABELLED: Depression and obesity are important in children because they affect health in childhood and later life. The exact relationship between obesity and depression, especially in children, remains undefined. PATIENTS AND METHODS: Using a cross-sectional chart review design, our study looked at a weight management clinic-based sample of 117 obese children, 7 to 17 years old, to determine the relationship between absolute BMI and depression as measured by the Children's Depression Index (CDI) while accounting for confounders, such as the child's medical problems, physical activity, and family structure. RESULTS: There was no correlation between depression as measured by the CDI and increasing BMI in obese children seeking weight management. However, we did demonstrate a positive correlation between depression and paternal absence and daily television/computer/video game time. CONCLUSIONS: Clinicians should encourage decreasing screen time and might consider family therapy for obese children in families that lack paternal involvement.

Practices associated with weight loss versus weight-loss maintenance results of a national survey.

BACKGROUND: Few studies have examined the weight-control practices that promote weight loss and weight-loss maintenance in the same sample. PURPOSE: To examine whether the weight control practices associated with weight loss differ from those associated with weight-loss maintenance. METHODS: Cross-sectional survey of a random sample of 1165 U.S. adults. The adjusted associations of the use of 36 weight-control practices in the past week with success in weight loss (≥10% lost in the past year) and success in weight-loss maintenance (≥10% lost and maintained for ≥1 year) were examined. RESULTS: Of the 36 practices, only 8 (22%) were associated with both weight loss and weight-loss maintenance. Overall, there was poor agreement (kappa=0.22) between the practices associated with weight loss and/or weight-loss maintenance. For example, those who reported more often following a consistent exercise routine or eating plenty of low-fat sources of protein were 1.97 (95% CI=1.33, 2.94) and 1.76 (95% CI=1.25, 2.50) times more likely, respectively, to report weight-loss maintenance but not weight loss. Alternatively, those who reported more often doing different kinds of exercises or planning meals ahead of time were 2.56 (95% CI=1.44, 4.55) and 1.68 (95% CI=1.03, 2.74) times more likely, respectively, to report weight loss but not weight-loss maintenance. CONCLUSIONS: Successful weight loss and weight-loss maintenance may require two different sets of practices. Designing interventions with this premise may inform the design of more effective weight-loss maintenance interventions.