Subtyping youngsters with obesity: A theory-based cluster analysis.

Psychological mechanisms play a crucial role in explaining weight gain. Aim of the present study was to identify subtypes in youngsters with obesity in line with these mechanisms. Defining homogeneous clusters within this heterogeneous group provides relevant information for personalized treatments. Data were collected in N = 572 participants (51% boys, aged 7-19) with extreme obesity (%BMI M = 187.8; SD = 30.9) recruited in an inpatient treatment centre. Based on psychological models of overweight/obesity, the Affect Regulation Model, the Reward Deficiency Model and The Dual Pathway Model, cluster variables were selected assessing emotional eating, reward reactivity and regulative capacities. Youngsters reported on emotional eating (DEBQ Emotional Eating) and reward sensitivity (BAS), while parents reported on children's regulative Executive Functions (BRIEF). Characteristics of the different clusters were examined concerning weight variables (pre and post treatment) and variables indexing problematic eating (DEBQ External Eating, Ch-EDE), affect regulation (FEEL-KJ) and depressive symptoms (CDI). Hierarchical cluster analyses supported the presence of three clusters, further evaluated by K-means cluster analyses. The cluster solutions differed according to age and sex (boys 7-13, boys 14-19, girls 7-13, girls 14-19). In all four age and gender subsamples, an "Emotional Eating" cluster displaying a vulnerable profile (high depression, maladaptive emotion regulation, problematic eating) and a "Reward Deficiency" cluster displaying a more resilient profile were detected. In girls 7-13, a "Weak Executive Functioning" indicative of insufficient self-regulative capacities, showed moderate to high emotional problems and problematic eating. In the other subgroups, the "Mean Level Functioning" cluster also showed elevated emotional problems and problematic eating. Given that different clusters can be identified, and given that these clusters have different profiles on emotional problems and problematic eating, subtyping youngsters with severe obesity is indicated, setting the stage for personalized treatments.

Using confidence interval-based estimation of relevance to explore bottom-up and top-down determinants of problematic eating behavior in children and adolescents with obesity from a dual pathway perspective.

Prevalence of overweight and obesity in children and adolescents is high, not only in Western countries but also in developing countries. Efforts to improve prevention and treatment programs are needed. Given their essential role in weight problems, knowledge of determinants of problematic eating behavior ('External Eating' and 'Emotional Eating') is crucial for intervention development. Inspired by Appelhans' Dual Process Theory of Eating Behavior, the present study evaluated the importance of top-down regulative capacities and bottom-up reactivity, using the CIBER approach. CIBER is an innovative statistical approach to test the importance of behavior determinants, based on confidence intervals, instead of significance testing of point estimates. Survey data on different aspects of executive functioning (as indices of regulative capacities: Inhibition, Cognitive Flexibility, Emotional Control, Initiation, Working Memory, Planning/Organizing, Organization of materials, and Monitoring) and reward sensitivity (as an index of reactivity) were collected in a large sample of children and adolescents (n = 572) with severe obesity (adjBMI > 180%). Results showed that Emotional Eating is determined by Emotional Control, while External Eating is determined by Reward Sensitivity. The finding that differential mechanisms underlie different aspects of problematic eating suggests the need for using tailored intervention techniques to address altered reactivity and weak regulative capacities.

Mediating Mechanisms in Cognitive Behavioral Therapy for Childhood OCD: The Role of Dysfunctional Beliefs.

Reframing cognitions is assumed to play an important role in treatment for obsessive-compulsive disorder (OCD). However, there hardly is any empirical support for this assumption, especially for children. The aim of this study was to examine if changing dysfunctional beliefs is a mediating mechanism of cognitive behavioral therapy (CBT) for childhood OCD. Fifty-eight children (8-18 years) with OCD received CBT. Dysfunctional beliefs (OBQ-CV) and OCD severity (CY-BOCS) were measured pre-treatment, mid-treatment, post-treatment, and at 16-week follow-up. Results showed that OCD severity and dysfunctional beliefs decreased during CBT. Changes in severity predicted changes in beliefs within the same time interval. Our results did not support the hypothesis that changing dysfunctional beliefs mediates treatment effect. Future studies are needed to replicate these findings and shed more light on the role of explicit and implicit cognitions in treatment for childhood OCD.

Factors influencing the reinforcing value of fruit and unhealthy snacks.

OBJECTIVE: The present study investigated the reinforcing value of healthy and unhealthy snack food in adolescents (n = 108, aged 14-16 years). Moderation by access to different foods, sex and the personality trait reward sensitivity is tested. METHODS: In a computerized Food Reinforcement Task, adolescents could earn portions of a healthy and an unhealthy snack following an identical progressive reinforcement schedule for both food types. Reinforcing value of food was indexed by the number of button presses for each food type. Participants were allocated randomly to two-order condition: fruit-snack versus snack-fruit. Reward sensitivity was assessed with the Dutch age-downward version of Carver and White's BIS/BAS scale. RESULTS: Results showed that the reinforcing value of an unhealthy snack is higher than that of fruit, with participants making more button presses for unhealthy snacks, M = 1280.40, SD = 1203.53, than for fruit, M = 488.04, SD = 401.45, F(1,48) = 25.37, p < 0.001. This effect is stronger in boys (ß = -1367.67) than in girls (ß = -548.61). The effect is only present in the snack-fruit condition, not in the fruit-snack condition, indicating that access to food moderates the effect of food type. There is no evidence for moderation by reward sensitivity. CONCLUSIONS: Results point to the importance of simultaneously increasing barriers to obtain unhealthy food and promoting access to healthy food in order to facilitate healthy food choices.

Using a gamified monitoring app to change adolescents' snack intake: the development of the REWARD app and evaluation design.

BACKGROUND: As the snacking pattern of European adolescents is of great concern, effective interventions are necessary. Till now health promotion efforts in children and adolescents have had only limited success in changing adolescents' eating patterns and anthropometrics. Therefore, the present study proposes an innovative approach to influence dietary behaviors in youth based on new insights on effective behavior change strategies and attractive intervention channels to engage adolescents. This article describes the rationale, the development, and evaluation design of the 'Snack Track School' app. The aim of the app is to improve the snacking patterns of Flemish 14- to 16-year olds. METHODS: The development of the app was informed by the systematic, stepwise, iterative, and collaborative principles of the Intervention Mapping protocol. A four week mHealth intervention was developed based on the dual-system model with behavioral change strategies targeting both the reflective (i.e., active learning, advance organizers, mere exposure, goal-setting, monitoring, and feedback) and automatic processes (i.e., rewards and positive reinforcement). This intervention will be evaluated via a controlled pre-post design in Flemish schools among 1400 adolescents. DISCUSSION: When this intervention including strategies focused on both the reflective and automatic pathway proves to be effective, it will offer a new scientifically-based vision, guidelines and practical tools for public health and health promotion (i.e., incorporation of learning theories in intervention programs). TRIAL REGISTRATION: NCT02622165 registrated November 15, 2015 on clinicaltrials.gov.

Altered pharmacokinetics of R- and S-acenocoumarol in a subject heterozygous for CYP2C9*3.

OBJECTIVE: Our objective was to study the pharmacokinetics of R - and S -acenocoumarol in a subject who was highly sensitive to the anticoagulant effect of acenocoumarol. The subject was found to be heterozygous for CYP2C9*3. METHODS: The plasma pharmacokinetics of the acenocoumarol enantiomers was established after an oral dose of 8 mg of racemic acenocoumarol. Urine was collected to establish the formation clearance of the 6- and 7-hydroxy metabolites of R - and S -acenocoumarol. RESULTS: The pharmacokinetics of S -acenocoumarol in this subject differed greatly (oral clearance, 6%-10%; half-life of elimination, 400%-500%) from the values of a [wt/wt] control and from population values. R -acenocoumarol clearance was at the lower level of population values. The apparent formation clearances of the metabolites were low-approximately 10% of control activity for the hydroxylations (6- and 7-) of S -acenocoumarol and for the 7-hydroxylation of R -acenocoumarol. The rate of the 6-hydroxylation of R -acenocoumarol was about 50% of control values. CONCLUSION: The presence of even one copy of CYP2C9*3 reduces profoundly the metabolic clearance of S -acenocoumarol. As a result the first-pass effect of elimination is abolished and the maintenance time is increased. S -Acenocoumarol, which is normally clinically inactive, will now exert main anticoagulant activity.

Inulin hydrogels as carriers for colonic drug targeting. Rheological characterization of the hydrogel formation and the hydrogel network.

Free radical polymerization converts aqueous solutions of methacrylated inulin into cross-linked hydrogels. The purpose of this work was to study the hydrogel formation and to characterize the fully cured hydrogels. The gelation process of aqueous solutions of methacrylated inulin was monitored as a function of time by means of linear oscillatory shear measurements, at a fixed frequency and amplitude. The fully cured inulin hydrogels were characterized by measurement of the frequency-dependency of the linear elastic modulus G'. The effects of the degree of substitution and feed concentration of methacrylated inulin on both the gelation kinetics and the rigidity of the obtained hydrogels were determined. The effect of the concentration of the initiators of the radical polymerization reaction has been studied as well. The weight fraction of polymer which was not incorporated in the hydrogel networks was determined using the anthrone reaction, and physical chain entanglements were determined by solution viscosity measurements. The gelation kinetics and the elastic modulus were proportional to the degree of substitution and feed concentration of methacrylated inulin. Increasing concentrations of radical-forming compounds also accelerated the hydrogel formation, but lowered the elastic modulus of the obtained hydrogels. The amount of polymer chains incorporated in the hydrogel network seemed to be especially influenced by the degree of substitution of the derivatized inulin, and for a feed concentration of 27% w/w of methacrylated inulin, entanglements have to be accounted for. The gelation kinetics and the elastic modulus of inulin hydrogels are not only affected by the degree of substitution and the feed concentration of methacrylated inulin, but also by the concentration of the initiators of the free radical polymerization reaction.

Colonic drug targeting.

Specific targeting of drugs to the colon is recognized to have several therapeutic advantages. Drugs which are destroyed by the stomach acid and/or metabolized by pancreatic enzymes are slightly affected in the colon, and sustained colonic release of drugs can be useful in the treatment of nocturnal asthma, angina and arthritis. Treatment of colonic diseases such as ulcerative colitis, colorectal cancer and Crohn's disease is more effective with direct delivery of drugs to the affected area. Likewise, colonic delivery of vermicides and colonic diagnostic agents require smaller doses. This article is aimed at providing insight into the design considerations and evaluation of colonic drug delivery systems. For this purpose, the anatomy and physiology of the lower gastrointestinal tract are surveyed. Furthermore, the biopharmaceutical aspects are considered in relation to drug absorption in the colon and hence various approaches to colon-specific drug delivery are discussed.

The potent antioxidant activity of the vitamin K cycle in microsomal lipid peroxidation.

In the vitamin K cycle, vitamin K-hydroquinone, the active cofactor for gamma-glutamylcarboxylase, is continuously regenerated. The successive pathways contain oxidation of the hydroquinone to the epoxide, followed by reduction to the quinone and reduction to the hydroquinone. Vitamin K-hydroquinone is a potent radical scavenging species (Mukai et al., J Biol Chem 267: 22277-22281, 1992). We tested the potential antioxidant activity of the vitamin K cycle in lipid peroxidation reactions (thiobarbituric acid reactive substances, TBARS) in rat liver microsomes. As prooxidant we used Fe2+/ascorbate, NADPH-Fe3+/ATP, and NADPH/CCl4. Vitamin K (< or = 50 microM) on its own did not influence the formation of TBARS. In combination with 1 mM dithiothreitol (DTT), the reductive cofactor for the microsomal enzyme vitamin K epoxide reductase, vitamin K suppressed lipid peroxidation with a concentration that blocked the maximal response by 50% (IC50) of ca. 0.2 microM. Vitamin K1 (phylloquinone) and vitamin K2 (menaquinone-4) were equally active. Warfarin (5 microM) and chloro-vitamin K (50 microM), inhibitors of vitamin K epoxide reductase and gamma-glutamylcarboxylase, respectively, were able to completely abolish the antioxidant effect. Lipid peroxidation was inversely related to the amount of vitamin K hydroquinone in the reaction. Vitamin K epoxide reductase seemed sensitive to lipid peroxidation, with half of the activity being lost within 10 min during oxidation with NADPH/CCl4. The inactivation could be attenuated by antioxidants such as vitamin E, reduced glutathione, and menadione and also by a K vitamin in combination with DTT, but not by superoxide dismutase and catalase. The results show that the vitamin K cycle could act as a potent antioxidant, that the active species in all probability is vitamin K-hydroquinone, and that the primary reaction product is the semiquinone. The results also show that the reaction product is processed in the vitamin K cycle to regenerate vitamin K-hydroquinone.

Inulin hydrogels as carriers for colonic drug targeting: I. Synthesis and characterization of methacrylated inulin and hydrogel formation.

PURPOSE: Vinyl groups were introduced in inulin chains in order to form hydrogels of this sugar polymer by free radical polymerization. METHODS: Inulin was reacted with glycidyl methacrylate in N,N-dimethylformamide in the presence of 4-dimethylaminopyridine as catalyst. 1H and 13C NMR spectroscopy were used for the characterization of the obtained reaction product. Solid state 13C NMR spectroscopy revealed the conversion of the incorporated vinyl groups into covalent cross-links upon free radical polymerization of aqueous solutions of the derivatized inulin. RESULTS: During reaction of inulin with glycidyl methacrylate, transesterification occurred, leading to the direct attachment of the methacryloyl group to inulin. Consequently, the obtained reaction product is methacrylated inulin. The extent of chemical modification of inulin could be tuned by varying the molar ratio of glycidyl methacrylate to inulin in the reaction mixture. Aqueous solutions of methacrylated inulin were converted into cross-linked hydrogels by free radical polymerization using ammonium persulphate and N,N,N',N'-tetramethylethylenediamine as initiating system. CONCLUSIONS: Inulin hydrogels can be formed by free radical polymerization of aqueous solutions of methacrylated inulin.

Release of indomethacin from transparent oil-water gels.

Within the scope of evaluating transparent oil-water gels (TOW gel) as dermatological vehicles, the release of indomethacin from a model TOW gel into 1-dodecanol is studied at various pH levels of the water phase. Apparent partition coefficient determinations and flame photometrical measurements show that both indomethacin and its sodium salt, as the ion pair, migrate into the 1-dodecanol layer. The pH-dependent release-rate profile is explained in terms of the amount of readily diffusible drug in the water phase of the gel.

Microsomal lipoamide reductase provides vitamin K epoxide reductase with reducing equivalents.

This study was undertaken to search for the endogenous dithiol cofactor of the reductases of the vitamin K cycle. As a starting point, the redox-active lipophilic endogenous compounds lipoic acid and lipoamide were looked at. The study shows that microsomes contain NADH-dependent lipoamide reductase activity. Reduced lipoamide stimulates microsomal vitamin K epoxide reduction with kinetics comparable with those for the synthetic dithiol dithiothreitol (DTT). Reduced lipoic acid shows higher (4-fold) Km values. No reductase activity with lipoic acid was found to be present in microsomes or cytosol. The reduced-lipoamide-stimulated vitamin K epoxide reductase is as sensitive to warfarin and salicylate inhibition as is the DTT-stimulated one. Both vitamin K epoxide reductase and lipoamide reductase activity are recovered in the rough microsomes. NADH/lipoamide-stimulated vitamin K epoxide reduction is uncoupled by traces of Triton X-100, suggesting that microsomal lipoamide reductase and vitamin K epoxide reductase are associated. The results suggest that the vitamin K cycle obtains reducing equivalents from NADH through microsomal lipoamide reductase.