Facilitators and barriers to a dietitian-implemented blended care weight-loss intervention (SMARTsize): a qualitative study.

BACKGROUND: Dietitians play an important role in the intervention and prevention of being overweight and obesity. More and more blended care interventions are being implemented. The present study aimed to evaluate the delivery by Dutch dietitians of a multicomponent, evidence-based weight-loss programme (SMARTsize), including counselling for relapse prevention. The aim of this qualitative study was to identify facilitators and barriers to the delivery of SMARTsize. METHODS: Nine semi-structured interviews were conducted with 10 dietitians who participated in a larger implementation study. Each interview was recorded and transcribed verbatim. Determinants of theory of implementation, including characteristics of the user, the innovation, organisational context and setting, and innovation strategy guided interviews and analysis. Data were coded and analysed using the framework approach. RESULTS: According to dietitians, the SMARTsize intervention had a positive influence on patients. The main implementation facilitators were the availability of implementation materials, such as a manual, training in relapse prevention and social support from other dietitians. The main barriers to implementation were organisation and financial reimbursement of cooking classes, the belief that patients need more individual counselling in the starting phase, and the unsuitability for people with low levels of health literacy. CONCLUSIONS: Most dietitians considered that implementation of the SMARTsize intervention consisting of e-health, written information and cooking classes and face-to-face counselling is challenging but feasible. Further development of the SMARTsize intervention and implementation tools is needed to lower experienced barriers. It is also recommended that a version of the intervention to be developed that is suitable for patients with lower levels of health literacy.

Determinants of weight loss maintenance: a systematic review.

BACKGROUND: Discerning the determinants of weight loss maintenance is important in the planning of future interventions and policies regarding overweight and obesity. We have therefore systematically synthesized recent literature on determinants of weight loss maintenance for individuals with overweight and obesity. METHODS: With the use of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, prospective studies were identified from searches in PubMed and PsycINFO from 2006 to 2016. We included articles investigating adults with overweight and obesity undergoing weight loss without surgery or medication. Included articles were scored on their methodological quality, and a best-evidence synthesis was applied to summarize the results. RESULTS: Our search resulted in 8,222 articles of which 67 articles were selected. In total, 124 determinants were identified of which 5 were demographic, 59 were behavioural, 51 were psychological/cognitive and 9 were social and physical environmental determinants. We found consistent evidence that demographic determinants were not predictive of weight loss maintenance. Behavioural and cognitive determinants that promote a reduction in energy intake, an increase in energy expenditure and monitoring of this balance are predictive determinants. CONCLUSION: This review identifies key determinants in weight loss maintenance. However, more research regarding cognitive and environmental determinants of weight loss maintenance is needed to advance our knowledge on determinants of weight loss maintenance.

Predictors of need for help with weight loss among overweight and obese men and women in the Netherlands: a cross-sectional study.

BACKGROUND: Need for help is perceived as an important first step towards weight related health-care use among overweight and obese individuals and several studies have reported gender as an important predisposing characteristic of need for help. Therefore, the goal of the current study is to gain insight into factors that might determine need for help for weight loss in men and women. METHODS: In the current study, data from the Dutch cross-sectional survey Health Monitor 2012 was used. Overweight and obese men (N = 2218) and women (N = 2002) aged 19-64 years were selected for the current study. Potential predictors of need for help were age, ethnicity, marital status, educational level, perceived health, weight status, comorbidities, physical activity level, and income. Multiple logistic regression analyses were conducted separately among men and women to establish prediction models of need for help for weight loss. RESULTS: The mean age of the adult women in this study population was 47.7 years and 68% was medium educated, whereas the mean age of men was 49.0 years and 63.0% was medium educated. Of the respondents, 24.9% indicated they either felt a need for help for weight loss, 6.4% already received help and 68.7% felt no need for help. Women were more likely to indicate a need for help than men (OR = 2.17). Among both genders, need for help was significantly predicted by obesity (ORmen = 3.80, ORwomen = 2.20) and "poor" perceived health (ORmen = 2.14, ORwomen = 1.94). Besides, "unmarried" (ORmen = 1.57) and suffering from comorbidities (ORmen = 1.26) predicted need for help among men. Whereas among women, need for help was predicted by younger age (i.e. 19-34 years (ORwomen = 2.07) and 35-49 years (ORwomen = 1.35)). CONCLUSION: The current study revealed specific predictors of need for help for weight loss for men and women. Among men, the strongest predictors were obesity and poor perceived health, whereas among women need for help was most strongly predicted by obesity and young age. Insight into these specific predictors enables health professionals to reach overweight individuals with a need for help for weight loss by connecting their need to available support.

Process evaluation of FATaintPHAT, a computer-tailored intervention to prevent excessive weight gain among Dutch adolescents.

UNLABELLED: Process evaluations can help us to better interpret intervention effects and provide guidance in improving interventions. This study describes the use and appreciation of FATaintPHAT, a computer-tailored intervention to prevent excessive weight gain in adolescents and link these data to the intervention effects. Use and appreciation were assessed among students (12-13 years old) from the intervention group of the FATaintPHAT evaluation study, using computer log (n = 458) and questionnaire data (n = 233, 48% response). Differences in use and appreciation between socio-demographic groups (gender, education, ethnicity, weight category), and associations with behavioural outcomes were analysed using descriptive and regression analyses. The results showed that a majority of the students (81%) was exposed to all intervention modules and 73% reported to have put the advice into practise. Half and one-third of the students appreciated the tailored advice positively and neutrally, respectively. Students attending vocational training appreciated FATaintPHAT better than students attending university preparation education. No associations were found between behavioural outcomes with appreciation and use. In conclusion, the school-based FATainPHAT intervention was used and appreciated well among adolescents. The fact that the intervention was appreciated better among the lower compared with higher educated students indicates that the technique of computer-tailoring is also suitable for lower educated students. TRIAL REGISTRATION: Netherlands Trial Registry, ISRCTN 15743786.

The effects of using a nutrition logo on consumption and product evaluation of a sweet pastry.

Nutrition logos have received a great deal of attention to stimulate people to eat a healthier diet. However, very little is known neither about actual consumption behavior related to nutrition logos nor about potential compensatory eating behaviors due to nutrition logos. The aim of this study was to assess the effects of using an existing nutrition logo on consumption and product evaluation of a chocolate mousse cake. A cross-over design was applied with two conditions: a condition with a logo and a condition without a logo. Participants were females recruited in the university community (n = 36, mean age 22.6 ± 6.3). Data on consumption, tastefulness, perceived healthiness, dietary restraint and Body Mass Index were collected. No significant differences between conditions were found on consumption and tastefulness. The cake was rated as significantly less unhealthy in the logo condition. In conclusion, results cannot be extrapolated to other products, especially not to products that are perceived as healthy. In this study, the use of a nutrition logo did not result in an increased consumption and had no effect on the rating of taste of a sweet pastry among females from the university community.

The internet and nutrition education: challenges and opportunities.

OBJECTIVE: To review the possibilities of using the Internet and especially the World Wide Web (WWW) in nutrition education. RESULTS: A healthy existence is partly dependent on dietary behaviours. One way to promote health-promoting dietary habits is nutrition education. In the last decades several potentially important new channels for health communication and nutrition education have emerged, with the Internet and its WWW as the most striking example. The introduction and growth of the WWW has enabled swift and inexpensive distribution of nutrition education expertise and materials. Furthermore, the WWW has also been used for tailoring nutrition education to the personal characteristics of the user. Only few studies have investigated the effects of generic web-based nutrition education, while web-based computer-tailored nutrition education has been studied in randomised controlled trials, with promising but mixed results. Two important challenges for web-based nutrition education interventions are to realise sufficient exposure and to ensure sufficient source reliability and credibility. CONCLUSIONS: Next to the great opportunities, there are many challenges for web-based nutrition education. Some evidence for effects of web-based computer-tailored nutrition education has been reported, but more research is needed to obtain evidence for the effectiveness in real-life situations.

Similar ultrastructural distribution of the 5-HT(2A) serotonin receptor and microtubule-associated protein MAP1A in cortical dendrites of adult rat.

As visualized by light and electron microscopic immunocytochemistry, the distribution of the neuronal serotonin-2A (5-HT(2A)) receptor is mainly intracellular throughout adult rat brain. This localization is particularly striking in the pyramidal cells of cerebral cortex, the dendrites of which are intensely immunoreactive, but without any labeling of their spines. In view of recent yeast two-hybrid and biochemical results suggesting an association of 5-HT(2A) receptors with the cytoskeletal microtubule-associated protein MAP1A, the respective subcellular distributions of the receptors and of MAP1A were compared by quantitative electron microscopic immunocytochemistry in dendrites of adult rat frontoparietal cortex. Counts of silver-intensified immunogold particles revealed a higher density of 5-HT(2A) receptors in smaller rather than larger dendrites, and an apportionment between pre-defined compartments representing the plasma membrane and the cytoplasm that was proportional to the relative surface area of these compartments. MAP1A immunoreactivity also predominated in smaller versus larger dendrites, but with a slightly lower proportion of labeling in the plasma membrane versus cytoplasmic compartment. The co-localization of 5-HT(2A) receptors and MAP1A protein in the same dendrites could be demonstrated in double immunolabeling experiments. These results confirmed the predominantly somato-dendritic, intracellular localization of 5-HT(2A) receptors in cerebral cortex, showed their higher concentration in distal as opposed to proximal dendrites, and suggested their potential association to the cytoskeleton in cortical neurons in vivo. Such a distribution of 5-HT(2A) receptors reinforces our earlier hypothesis that 5-HT(2A) receptors participate in intraneuronal signaling processes involving the cytoskeleton, and raises the possibility that their activation could be dependent upon that of another co-localized, plasma membrane-bound, 5-HT receptor.

Differential modes of agonist binding to 5-hydroxytryptamine(2A) serotonin receptors revealed by mutation and molecular modeling of conserved residues in transmembrane region 5.

Site-directed mutagenesis and molecular modeling were used to investigate the molecular interactions involved in ligand binding to, and activation of, the rat 5-hydroxytryptamine(2A) (5-HT(2A)) serotonin (5-HT) receptor. Based on previous modeling studies utilizing molecular mechanics energy calculations and molecular dynamics simulations, four sites (S239[5.43], F240[5.44], F243[5.47], and F244[5.48]) in transmembrane region V were selected, each predicted to contribute to agonist and/or antagonist binding. The F243A mutation increased the affinity of (+/-)4-iodo-2, 5-dimethoxyphenylisopropylamine, decreased the binding of alpha-methyl-5HT, N-omega-methyl-5HT, ketanserin, ritanserin, and spiperone and had no effect on the binding of 5-HT and 5-methyl-N, N-dimethyltryptamine. The F240A mutant had no effect on the binding of any of the ligands tested, whereas F244A caused an agonist-specific decrease in binding affinity (3- to 10-fold). S239A caused a 6- to 13-fold decrease in tryptamine-binding affinity and a 5-fold increase in affinity of 4-iodo-2, 5-dimethoxyphenylisopropylamine. A subset of the agonists used in binding studies were used to determine the efficacies and potencies of these mutants to activate phosphoinositide hydrolysis. The F243A and F244A mutations reduced agonist stimulated phosphoinositide hydrolysis, whereas the S239A and F240A mutations had no effect. There was little correlation between agonist binding and second messenger production. Furthermore, molecular dynamics simulations, considering these data, produced ligand-bound structures utilizing substantially different bonding interactions even among structurally similar ligands (differing by as little as one methyl group). Taken together, these results suggest that relatively minor changes in either receptor or ligand structure can produce drastic and unpredictable changes in both binding interactions and 5-HT(2A) receptor activation. Thus, our finding may have major implications for the future and feasibility of receptor structure-based drug design.

A highly conserved aspartic acid (Asp-155) anchors the terminal amine moiety of tryptamines and is involved in membrane targeting of the 5-HT(2A) serotonin receptor but does not participate in activation via a "salt-bridge disruption" mechanism.

Discovering the molecular and atomic mechanism(s) by which G-protein-coupled receptors (GPCRs) are activated by agonists remains an elusive goal. Recently, studies examining two representative GPCRs (rhodopsin and alpha(1b)-adrenergic receptors) have suggested that the disruption of a putative "salt-bridge" between highly conserved residues in transmembrane (TM) helix III, involving aspartate or glutamate, and helix VII, involving a basic residue, results in receptor activation. We have tested whether this is a general mechanism for GPCR activation by constructing a model of the 5-hydroxytryptamine (5-HT)(2A) receptor and characterizing several mutations at the homologous residues (Asp-155 and Asn-363) of the 5-HT(2A) serotonin receptor. All of the mutants (D155A, D155N, D155E, D155Q, and S363A) resulted in receptors with reduced basal activity; in no case was evidence for constitutive activity revealed. Structure-function studies with tryptamine analogs and various Asp-155 mutants demonstrated that Asp-155 interacts with the terminal, and not indole, amine moiety of 5-HT(2A) agonists. Interestingly, the D155E mutation interfered with the membrane targeting of the 5-HT(2A) receptor, and an inverse relationship was discovered when comparing receptor activation and targeting for a series of Asp-155 mutants. This represents the first known instance in which a charged residue located in a putative TM helix alters the membrane targeting of a GPCR. Thus, for 5-HT(2A) receptors, the TMIII aspartic acid (Asp-155) is involved in anchoring the terminal amine moiety of indole agonists and in membrane targeting and not in receptor activation by salt-bridge disruption.

Structure and function of the third intracellular loop of the 5-hydroxytryptamine2A receptor: the third intracellular loop is alpha-helical and binds purified arrestins.

Understanding the precise structure and function of the intracellular domains of G protein-coupled receptors is essential for understanding how receptors are regulated, and how they transduce their signals from the extracellular milieu to intracellular sites. To understand better the structure and function of the intracellular domain of the 5-hydroxytryptamine2A (5-HT2A) receptor, a model G(alpha)q-coupled receptor, we overexpressed and purified to homogeneity the entire third intracellular loop (i3) of the 5-HT2A receptor, a region previously implicated in G-protein coupling. Circular dichroism spectroscopy of the purified i3 protein was consistent with alpha-helical and beta-loop, -turn, and -sheet structure. Using random peptide phage libraries, we identified several arrestin-like sequences as i3-interacting peptides. We subsequently found that all three known arrestins (beta-arrestin, arrestin-3, and visual arrestin) bound specifically to fusion proteins encoding the i3 loop of the 5-HT(2A) receptor. Competition binding studies with synthetic and recombinant peptides showed that the middle portion of the i3 loop, and not the extreme N and C termini, was likely to be involved in i3-arrestin interactions. Dual-label immunofluorescence confocal microscopic studies of rat cortex indicated that many cortical pyramidal neurons coexpressed arrestins (beta-arrestin or arrestin-3) and 5-HT2A receptors, particularly in intracellular vesicles. Our results demonstrate (a) that the i3 loop of the 5-HT2A receptor represents a structurally ordered domain composed of alpha-helical and beta-loop, -turn, and -sheet regions, (b) that this loop interacts with arrestins in vitro, and is hence active, and (c) that arrestins are colocalized with 5-HT2A receptors in vivo.

The molecular biology of serotonin receptors: therapeutic implications for the interface of mood and psychosis.

This review summarizes the molecular biology of serotonin (5-HT; 5-hydroxytryptamine) receptors and indicates the potential relevance of this information for the treatment of mood and psychotic disorders. At least 15 separate subtypes of 5-HT receptors have been identified by molecular cloning techniques to be distinct genetic entities. Subtle differences in the primary amino acid sequences of these receptors can yield large differences in ligand selectivity. Additionally, it has recently been discovered that drugs such as atypical antipsychotic drugs and serotonin-selective reuptake inhibitors may interact with a large number of heretofore unknown 5-HT receptors. Thus clozapine, for instance, has high affinity for at least four separate 5-HT receptors, and it is unknown which of these receptors is essential for its unique therapeutic efficacy. One way to approach these questions is to test subtype-selective agents, although there are few of these currently available. Approaches to the design of subtype-selective ligands are described, including structure-based drug design and combinatorial approaches. Modes of regulation of 5-HT receptors are also summarized, and it is emphasized that antipsychotic drugs and antidepressants likely exert their effects via nontranscriptional and posttranslational means. Understanding the cellular mechanisms by which 5-HT receptors are regulated by psychopharmacologic agents is likely to yield novel insights into drug action.

5-Hydroxytryptamine2-family receptors (5-hydroxytryptamine2A, 5-hydroxytryptamine2B, 5-hydroxytryptamine2C): where structure meets function.

5-Hydroxytryptamine2 (serotonin2, 5-HT2)-family receptors are important for mediating many physiological functions, including vascular and nonvascular smooth muscle contraction, platelet aggregation, modulation of perception, mood, anxiety, and feeding behavior. A large number of psychopharmaceuticals, including atypical antipsychotic drugs, antidepressants, anxiolytics, and hallucinogens, mediate their actions, at least in part, via interactions with various 5-HT2-family receptors. This review article summarizes information about structure-function aspects of 5-HT2-family receptors. Evidence is presented that implies that conserved aromatic and charged residues are essential for ligand binding to 5-HT2A receptors. Additionally, findings are reviewed that are consistent with the hypothesis that residues located in intracellular loops 2 and 3 (i2 and i3) mediate coupling to specific G(alpha)-subunits such as G(alpha q). Studies are reviewed that suggest that 5-HT2-family receptors may be down-regulated by both agonists and antagonists, and usually this down-regulation is due to post-transcriptional mechanisms. Finally, a model for regulation of 5-HT2-family receptors by receptor-mediated endocytosis is advanced, and the particular structural features responsible for the various endocytotic pathways are emphasized. Taken together, these results suggest that discrete domains of the receptor structure are important for ligand binding, G-protein coupling, and internalization.

Serotonin 5-HT2A receptors: molecular biology and mechanisms of regulation.

Serotonin 5-HT2A receptors are essential for a large number of physiological functions in the central nervous system and periphery. This review article summarizes our current knowledge of the molecular biology and mechanisms of regulation of 5-HT2A receptors. The mode of drug binding using data derived from molecular modeling and site-directed mutagenesis is described. The cellular and subcellular localization of 5-HT2A receptors is described, and the concentration of 5-HT2A receptors on apical dendrites of pyramidal neurons is emphasized. Various modes of regulation of 5-HT2A receptors are also summarized, including transcriptional, post-translational and mRNA editing processes. Finally, an integrated model of 5-HT2A receptor regulation that involves various protein kinases (protein kinase C, G-protein receptor kinases), arrestins, clathrin-coated vesicles, endosomes and lysosomes. The relevance of these pathways for antidepressant and antipsychotic drug actions is emphasized.

Secretory vesicles are the intracellular reservoir of complement receptor 1 in human neutrophils.

The subcellular localization of complement receptor 1 (CR1) was investigated in human neutrophils. CR1 was located exclusively in the light membrane fractions containing secretory vesicles and plasma membranes in Percoll density gradients of unperturbed neutrophils. Separation of plasma membranes from secretory vesicles by high-voltage free-flow electrophoresis of the light membranes from the Percoll gradient revealed that more than 80% of the CR1 was located intracellularly in secretory vesicles. After weak stimulation of neutrophils, the increase in CR1 surface expression closely paralleled both surface increase of known secretory vesicle membrane Ags and the release of matrix proteins from secretory vesicles. More potent stimulation of the neutrophils did not enhance CR1 surface expression further, in agreement with the lack of CR1 in granules as demonstrated on Percoll gradient. CR3 (Mac-1), which has been shown to be located both in secretory vesicles and in neutrophil granules, was up-regulated in parallel with CR1 after weak stimuli, whereas a profound increase of CR3 was observed after more potent stimuli in accordance with granule mobilization. These results identify secretory vesicles as the reservoir of CR1, which translocates to the plasma membrane after weak stimulation, and underscore the functional significance of this recently identified organelle.

Brugia malayi: acquired resistance to microfilariae in BALB/c mice correlates with local Th2 responses.

The role of specific Th subsets in the regulation of acquired resistance to the filarial parasite Brugia malayi is not known. We examined pathologic and cytokine responses in filarial antigen-sensitized BALB/c mice inoculated intraperitoneally with live microfilariae. Animals immunized three times with soluble microfilarial antigen demonstrated accelerated clearance of live parasites (12 +/- 5% of parasites recovered from the peritoneal cavity 4 days after inoculation vs 57 +/- 6% in controls, P < 0.001). Elimination of microfilariae by immunized mice was associated with local eosinophilia (1.5 x 10(7) eosinophils/ml peritoneal wash fluid compared with 2 x 10(5) eosinophils/ml in unimmunized animals), development of local eosinophil-containing granulomas, and elevated serum IgE levels (7.0 +/- 1.4 vs 2.1 +/- 0.9 micrograms/ml in controls, P < 0.01). CD4+ cells from the site of parasite challenge produced Th2-associated cytokines exclusively (IL-4 and IL-5, not IFN-gamma and IL-2) in response to Brugia antigen, whereas spleen and lymph node cells produced both Th1- and Th2-associated cytokines. Mice immunized a single time with microfilarial antigen did not clear parasites in this time, and peritoneal exudate cells from these animals produced IFN-gamma but not IL-5. These results indicate that acquired resistance to B. malayi microfilariae in mice is associated with induction of a Th2 and not a Th1 response at the site of parasite elimination.

Echinococcus multilocularis: variation among samples of cyst fluid in binding of parasite-specific antibodies.

Some of the factors influencing the sensitivity of ELISA in serodiagnosis of infections with Echinococcus multilocularis were examined. The results obtained suggest that, in contrast to E. granulosus, the variability in the antibody-binding capacity of various samples of cyst fluid of E. multilocularis cannot be explained by differences among parasite strains, species of host, cyst locations within the host, cyst fertility or protein concentration of the sample.

Echinococcus multilocularis: responses to infection in Mongolian gerbils.

Mongolian gerbils (Meriones unguiculatus) inoculated intraperitoneally with three acephalic cysts of Echinococcus multilocularis were very susceptible to infection. Aspects of the responses of gerbils to this infection were examined to determine if they could be related to the progress of the infection. Hematologic changes observed during the infection included anemia, reticulocytosis, lymphocytopenia, neutrophilia, monocytosis, and eosinopenia; these changes were related to the size of the infection. Infected gerbils also produced specific protein-A binding antibodies to E. multilocularis. At 14 weeks after inoculation, infected gerbils showed splenomegaly and somewhat elevated serum transaminase levels, although serum 5'-nucleotidase levels were normal.