Switching between foods is reliably associated with intake across eating events in children.

Emerging evidence suggests switching between foods during an eating event is positively associated with intake. However, it is unclear whether switching is a stable behavior that predicts consumption across multiple eating events. The current study explored whether switching is consistent within children and reliably associated with intake across varied eating events. We analyzed data from 88 (45 F), 7-8-year-old children without obesity participating in a 7-visit prospective cohort study (ClinicalTrials.gov NCT03341247). Amount consumed and energy intake were measured at 4 separate meals of foods that varied by portion sizes served. Meals included macaroni and cheese, chicken nuggets, broccoli, and grapes (all 0.7-2.5 kcal/g). Children's intake was also assessed during 2 eating in the absence of hunger (EAH) paradigms separated by ≥ 1 year. The EAH paradigm included 9 sweet and savory snack foods (all 1.9-5.7 kcal/g). All eating events were video-recorded and switching was assessed by counting the number of times a child shifted between different food items. Results demonstrated that switching was reliably associated with intake at both the meals and the EAH paradigms (ps < 0.01). Specifically, at meals each additional switch was associated with 11.7 ± 1.3 kcal (7.7 ± 0.8 g) more consumed, and during EAH each additional switch was associated with 8.1 ± 2.1 kcal (2.1 ± 0.5 g) more consumed. Switching behavior was also moderately consistent across meals (ICC = 0.70) and EAH paradigms (ICC = 0.50). However, switching at meals was not related to switching at EAH paradigms. This study demonstrates the consistency of switching behavior and its reliable association with intake across eating events, highlighting its potential to contribute to chronic overconsumption and childhood obesity.

Child eating behaviors are consistently linked to intake across meals that vary in portion size.

Prior studies evaluating a single meal in children characterized an "obesogenic" style of eating marked by larger bites and faster eating. It is unclear if this style is consistent across portion sizes within children so we examined eating behaviors in 91 children (7-8 years, 45 F) without obesity (BMI<90th percentile). Children consumed 4 ad libitum meals in the laboratory consisting of chicken nuggets, macaroni, grapes, and broccoli that varied in portion size (100%, 133%, 166%, 200%) with a maximum of 30 min allotted per meal. Anthropometrics were assessed using age and sex adjusted body mass index (BMI) percentile and dual energy x-ray absorptiometry. Bites, sips, active eating time, and meal duration were coded from meal videos; bite size (kcal and g/bite), proportion of active eating (active eating time/meal duration), and eating rate (kcal and g/meal duration) were computed. Intraclass correlation coefficients (ICC) showed that most eating behaviors were moderately consistent across portions (>0.50). The consistency of associations between eating behaviors and total meal intake and adiposity were assessed with general linear models adjusted for food liking, pre-meal fullness, age, and sex. Across all portions, more bites, faster eating rate, and longer meal duration were associated with greater intake. While higher BMI percentile was associated with faster eating rates across all meals, greater fat mass index was only associated with faster eating at meals with portions typical for children (i.e., 100% and 133%). In a primarily healthy weight sample, an 'obesogenic' style of eating was a consistent predictor of greater intake across meals that varied in portion size. The consistent relationship of these behaviors with intake makes them promising targets to reduce overconsumption.

Children's inhibitory control abilities in the presence of rewards are related to weight status and eating in the absence of hunger.

The Reflective-Impulsive Dual Processes Model suggests that overeating occurs when the temptation to consume food overrides inhibitory control processes. However, how rewards interact with inhibitory control and their relation to children's weight status and food intake is not understood. Here, 7-to-11-year-old children (n = 66; 32 overweight/obese) completed two versions (baseline [i.e., non-reward incentivized/control] and reward incentivized [food, money, no reward]) of a Go/Nogo task. Intake of palatable foods in the absence of hunger (i.e., eating in the absence of hunger-EAH) was measured following a standardized meal. A drift diffusion model was used to characterize children's performance parameters on the Go/Nogo. On the baseline Go/Nogo, children with higher weight status responded more cautiously, but on reward trials for food/money children were more cautions and made more false alarms relative to the no reward condition. Energy intake during EAH positively correlated with FA errors for food and money vs. no reward, but sex moderated this effect such that FA positively associated with EAH in girls but not boys. Independent of sex, FA for money vs. no reward and food vs. money were both positively associated with energy consumed during EAH. These results suggest that the presence of food and money rewards impair inhibitory control processing, especially in children with higher weight status. Further, increased inhibitory control impairment in response to food rewards, specifically, may be a risk factor for disinhibited eating in girls. Though preliminary, results may be useful in the development of targeted treatments to help moderate excess consumption in children.

Increased brain and behavioural susceptibility to portion size in children with loss of control eating.

BACKGROUND: Portion size influences intake (i.e. the portion size effect [PSE]), yet determinants of susceptibility to the PSE are unclear. OBJECTIVE: We tested whether children who reported an episode of loss of control (LOC) eating over the last 3 months would be more susceptible to the PSE and would show differential brain responses to food cues compared with children with no-LOC. METHODS: Across five sessions, children (n = 47; 7-10 years) consumed four test meals at 100%, 133%, 167% and 200% conditions for portion size and completed a functional magnetic resonance imaging scan while viewing pictures of foods varied by portion size and energy density (ED). Incidence of LOC over the past 3 months was self-reported. Random coefficient models were tested for differences in the shape of the PSE curve by LOC status. A whole-brain analysis was conducted to determine response to food cues during the functional magnetic resonance imaging. RESULTS: Reported LOC (n = 13) compared with no-LOC (n = 34) was associated with increased susceptibility to the PSE, as evidenced by a positive association with the linear slope (P < 0.005), and negative association with the quadratic slope (P < 0.05) of the intake curve. Children who reported LOC compared with no-LOC showed increased activation in the left cerebellum to small relative to large portions (P < 0.01) and right cerebellum to High-ED relative to Low-ED food cues (P < 0.01). CONCLUSION: Children who reported LOC were more susceptible to the PSE and showed alterations in food-cue processing in the cerebellum, a hindbrain region implicated in satiety signalling.

Food or money? Children's brains respond differently to rewards regardless of weight status.

BACKGROUND: Brain responses to both food and monetary rewards have been linked to weight gain and obesity in adults, suggesting that general sensitivity to reward contributes to overeating. However, the relationship between brain reward response and body weight in children is unclear. OBJECTIVE: The objective of this study was to assess the brain's response to multiple rewards and the relationship to body weight in children. METHODS: We tested this by performing functional magnetic resonance imaging while children (7- to 11-years-old; healthy weight [n = 31], overweight/obese [n = 30]) played a modified card-guessing task to assess blood-oxygen-level-dependent (BOLD) response to anticipating and winning food and money rewards. Functional magnetic resonance imaging data were analysed using a region of interest and exploratory whole-brain approach. RESULTS: Region of interest results demonstrated increased BOLD response in the striatum to anticipating food vs. neutral (control) and winning money vs. neutral. Whole-brain data showed that winning money vs. food was associated with increased activation in the striatum, as well as regions associated with cognitive control and emotion. Notably, for both approaches, these effects were independent of child weight status. Additionally, children's reported food responsiveness and emotional overeating were negatively correlated with the BOLD response in the left cingulate gyrus for winning food vs. money. CONCLUSION: Overall, findings from this study show that regions associated with reward, cognitive control and emotion may play a role in the brain's response to food and money rewards, independently of how much the child weighs. These findings provide insight into reward sensitivity in children, which may have implications for understanding overeating and the development of obesity.

Observed parent-child feeding dynamics in relation to child body mass index and adiposity.

BACKGROUND: Restrictive feeding is associated with child overweight; however, the majority of studies used parent-report questionnaires. OBJECTIVES: The relationship between child adiposity measures and directly observed parent and child behaviours were tested using a novel behavioural coding system (BCS). METHODS: Data from 109 children, participants in a twin study and their mothers, were analyzed. Parent-child dyads were video-recorded twice in the laboratory, while children ate ad libitum from a buffet lunch. Mother and child behaviours were assessed using the BCS. Height, body weight and body fat were directly measured for each child. Associations between child adiposity measures and average BCS behaviour (i.e. pooled across visits) were tested using partial correlations adjusting for child age. RESULTS: Regarding discouragement prompts, child body mass index (BMI) z-score was significantly associated with a greater rate of total discouragements (per minute, min-1 ), nonverbal discouragements (min-1 ) and temporary (delay) discouragements (min-1 ) (p < 0.05). Child percent body fat was associated with greater nonverbal discouragements (min-1 ). Regarding encouragement prompts, child BMI z-score was significantly associated with a greater rate of total encouragements (min-1 ), nonverbal encouragements (min-1 ) and reward encouragements (min-1 ). Child BMI z-score and percent body fat were both positively associated with greater maternal health encouragements (min-1 ). Associations with encouragement to eat prompts were no longer significant when accounting for the dependence among twins (being part of the same family). CONCLUSIONS: Heavier children received greater maternal discouragements to eat and, with qualifications, encouragements to eat. The role of nonverbal parenting cues warrants further research regarding child eating regulation and obesity.

Reduced neural responses to food cues might contribute to the anorexigenic effect of acute exercise observed in obese but not lean adolescents.

Acute exercise has been found to reduce subsequent energy intake in obese adolescents. Although it has been suggested that some neural pathways are involved in this post-exercise energy intake regulation, it remains unknown whether the post-exercise attentional response to food cues differs as a function of weight status. We hypothesize that there will be a reduction in the neural response to food cues as a result of exercise in obese adolescents, but not in their lean counterparts. Fourteen obese and 14 lean adolescent boys (12-15 years) were randomized (within-subjects design) to remain seated (CON) or to exercise 45 minutes at 65% of their maximal capacities (EX). After the exercise or sitting period, the adolescents' cognitive engagement in the processing of food vs. non-food cues was assessed during an attentional computer-based task with electroencephalography (EEG) recording. An ad libitum lunch meal was offered and appetite feelings were assessed (visual analog scales). There was no main effect of condition on energy intake in lean subjects, but obese adolescents ate significantly less following EX compared with CON (P<.05). There was no effect of condition or stimulus type (food vs. non-food) on the EEG-recorded amplitude of the P3b component in lean adolescents. However, the response to food cues was significantly reduced compared with non-food stimuli after exercise in obese participants (P<.01). Following EX, but not CON, total body weight, body mass index, and fat mass were inversely correlated with the EEG response to food-non-food stimuli (all P<.05). However, this response was not associated with ad libitum EI (both P>.1). Acute exercise favors decreased neural response to food cues compared with non-food cues in obese but not lean adolescents, suggesting differential effects of exercise on the neural processing of food cues based on weight status.

Brain regions implicated in inhibitory control and appetite regulation are activated in response to food portion size and energy density in children.

OBJECTIVE: Large portions of energy-dense foods drive energy intake but the brain mechanisms underlying this effect are not clear. Our main objective was to investigate brain function in response to food images varied by portion size (PS) and energy density (ED) in children using functional magnetic resonance imaging (fMRI). METHODS AND DESIGN: Blood-oxygen-level-dependent (BOLD) fMRI was completed in 36 children (ages 7-10 years) after a 2-h fast while viewing food images at two levels of PS (Large PS, Small PS) and two levels of ED (High ED, Low ED). Children rated perceived fullness pre- and post-fMRI, as well as liking of images on visual analog scales post-fMRI. Anthropometrics were completed 4 weeks before the fMRI. Large PS vs Small PS and High ED vs Low ED were compared with region-of-interest analyses using Brain Voyager v 2.8. RESULTS: Region-of-interest analyses revealed that activation in the right inferior frontal gyrus (P=0.03) was greater for Large PS vs Small PS. Activation was reduced for High ED vs Low ED in the left hypothalamus (P=0.03). Main effects were no longer significant after adjustment for pre-fMRI fullness and liking ratings (PS, P=0.92; ED, P=0.58). CONCLUSION: This is the first fMRI study to report increased activation to large portions in a brain region that is involved in inhibitory control. These findings may contribute to understanding why some children overeat when presented with large portions of palatable food.

Reduced neural response to food cues following exercise is accompanied by decreased energy intake in obese adolescents.

BACKGROUND: Acute exercise has been found to favor a transient anorexigenic effect in obese adolescents. Although the role of some gastro-peptides has been suggested as an explanation for this observed reduced energy intake after exercise, it is unknown whether neural pathways involved in the regulation of food intake are modulated in youth. METHODS: Body composition (dual-energy X-ray absorptiometry) and aerobic capacities were assessed in 19 obese adolescent boys. Participants were randomized to remain at rest in a sitting position (CON condition) or to exercise 45 min at 65% of their maximal capacities (EX condition) by the end of the morning. An attentional computer task with electroencephalography recording was completed immediately after the exercise or sitting period to measure an event-related component (P3b) reflecting the level of cognitive engagement in the processing of food cues. A lunch test-meal was offered ad libitum and appetite feelings assessed at regular intervals using visual analog scales. RESULTS: The 45-min cycling exercise set at 65% VO2max induced a mean energy expenditure of 399±75 kcal. Both absolute (P<0.05) and relative (P<0.001) subsequent energy intake were significantly reduced after EX (1037±260 and 639±256 kcal, respectively) compared with CON (1116±243 and 1011±239 kcal, respectively). The energy ingested derived from each macronutrient and self-reported appetite remained unchanged. Although the amplitudes of the P3b component evoked by food and non-food visual stimuli were not significantly different during CON, the response to food cues was significantly reduced compared with non-food stimuli after exercise (P<0.01). DISCUSSION: An acute exercise favors decreased neural response to food cues compared with non-food ones in obese adolescents that may contribute to their subsequently reduced energy intake.

A twin study of self-regulatory eating in early childhood: estimates of genetic and environmental influence, and measurement considerations.

OBJECTIVE: Children differ greatly in their ability to self-regulate food intake for reasons that are poorly understood. This laboratory-based twin study tested the genetic and environmental contributions to self-regulatory eating and body fat in early childhood. METHODS: A total of 69 4-7 year-old same-sex twin pairs, including 40 monozygotic and 29 dizygotic pairs, were studied. Self-regulatory eating was operationalized as the percentage compensation index (COMPX%), assessed by a 'preload' challenge in which lunch intake was measured following a low- (3 kcal) or high-calorie (159 kcal) drink. Body fat indexes also were measured. The familial association for COMPX% was estimated by an intraclass correlation, and biometric analyses estimated heritability. RESULTS: Children ate more at lunch following the low- compared with high-energy preload (P<0.001), although variability in COMPX% was considerable. Compensation was significantly poorer among African American and Hispanic compared with European American children, and among girls compared with boys. There was a familial association for self-regulatory eating (ρ = 0.23, P = 0.03) but no significant genetic component. In all, 22% of the variance in COMPX% was due to shared environmental 'household' factors, with the remaining variance attributable to child-specific 'unique' or 'random' environments. Poorer self-regulatory eating was associated with greater percent body fat (r = -0.21, P = 0.04). CONCLUSIONS: Self-regulatory eating was influenced by environmental factors, especially those differing among siblings. The absence of a significant genetic effect may reflect the age of the sample or could be artifactual due to measurement issues that need to be considered in future studies.

Generalized schemes for high-throughput manipulation of the Desulfovibrio vulgaris genome.

The ability to conduct advanced functional genomic studies of the thousands of sequenced bacteria has been hampered by the lack of available tools for making high-throughput chromosomal manipulations in a systematic manner that can be applied across diverse species. In this work, we highlight the use of synthetic biological tools to assemble custom suicide vectors with reusable and interchangeable DNA "parts" to facilitate chromosomal modification at designated loci. These constructs enable an array of downstream applications, including gene replacement and the creation of gene fusions with affinity purification or localization tags. We employed this approach to engineer chromosomal modifications in a bacterium that has previously proven difficult to manipulate genetically, Desulfovibrio vulgaris Hildenborough, to generate a library of over 700 strains. Furthermore, we demonstrate how these modifications can be used for examining metabolic pathways, protein-protein interactions, and protein localization. The ubiquity of suicide constructs in gene replacement throughout biology suggests that this approach can be applied to engineer a broad range of species for a diverse array of systems biological applications and is amenable to high-throughput implementation.

Divalproex extended-release in acute bipolar II depression.

BACKGROUND: Divalproex extended-release (divalproex-ER) is effective in acute mania, and limited data suggest divalproex may have efficacy in acute bipolar depression. METHODS: A 7-week, open-label trial of divalproex-ER monotherapy or adjunctive therapy was conducted in 28 outpatients (15 female, mean age 36.7+/-9.1, and mean duration of illness 22.1+/-11.1 years) with bipolar II depression (39% with rapid cycling course of illness within the prior year). Divalproex-ER was generally given as a single dose at bedtime, starting at 250mg and increased by 250mg every 4 days to symptom relief or adverse effects. Efficacy was assessed using weekly prospective Montgomery Asberg Depression Rating Scale (MADRS) scores. RESULTS: Overall, mean divalproex-ER final doses and serum concentrations were 1469mg/day and 80.1microg/mL, respectively. Mean MADRS scores (last observation carried forward) decreased significantly from baseline in patients in the overall group (from 30.1 to 15.2, p<.00001). The overall response rate was 54%. Divalproex-ER therapy was generally well tolerated, with no early discontinuations due to adverse events. LIMITATIONS: This study is limited by a small sample size and an open-label study design with no placebo control. CONCLUSIONS: Divalproex-ER as monotherapy and adjunctive therapy was well tolerated and yielded an overall response rate of 54% in bipolar II depression. Based on the results of this pilot study, randomized, double-blind, placebo-controlled studies of divalproex-ER in bipolar II depression are warranted.

Fill-tube-induced mass perturbations on x-ray-driven, ignition-scale, inertial-confinement-fusion capsule shells and the implications for ignition experiments.

On the first inertial-confinement-fusion ignition facility, the target capsule will be DT filled through a long, narrow tube inserted into the shell. microg-scale shell perturbations Delta m' arising from multiple, 10-50 microm-diameter, hollow SiO2 tubes on x-ray-driven, ignition-scale, 1-mg capsules have been measured on a subignition device. Simulations compare well with observation, whence it is corroborated that Delta m' arises from early x-ray shadowing by the tube rather than tube mass coupling to the shell, and inferred that 10-20 microm tubes will negligibly affect fusion yield on a full-ignition facility.

Maternal restriction of children's eating and encouragements to eat as the 'non-shared environment': a pilot study using the child feeding questionnaire.

OBJECTIVE: This pilot study tested whether maternal feeding attitudes and styles towards children are part of the 'shared' or 'non-shared' home environment. A secondary aim was to test whether within-family differences in maternal feeding attitudes and styles relate to within-family differences in child weight status. METHODS: Mothers of 3- to 7-year-old sibling pairs (N=15 pairs) completed the Child Feeding Questionnaire (CFQ), which assessed feeding attitudes (perceived responsibility, perceived child overweight and child weight concern) and feeding styles (monitoring, restriction and pressure to eat) towards children. Mothers rated each sibling separately. Child weight and height were measured and converted to body mass index (BMI) z-scores. Intraclass correlations tested the familial associations for each CFQ subscale. Pearson's correlations tested whether within-family differences in CFQ subscales were related to within-family differences in child BMI z-scores. RESULTS: Perceived responsibility (rho=0.77, P=0.0004), perceived child overweight (rho=0.99, P<0.0001) and monitoring (rho=0.57, P=0.01) showed significant familial correlations. Mothers reported significantly greater weight concern (r=0.85, P=0.02) and reduced pressure to eat (r=-0.80, P=0.03) towards heavier than thinner children within families. CONCLUSION: Whether or not maternal feeding practices are shared or non-shared components of the home environment depends on the specific feeding domain being measured. Restrictive feeding practices and encouragements to eat by mothers might be tested as non-shared environmental variables in genetics studies of childhood obesity.

Genetics of food intake and body composition: lessons from twin studies.

Twin studies are useful designs for decomposing genetic and environmental influences on traits, with the basic goal being to map variations in phenotypic similarity onto variances in genetic similarity. In this review, we provide an overview of twin studies that have been used to decompose the genetic and environmental influences behind body composition, eating style, and their covariation. Although many published reports have established that genes contribute anywhere from 50-90% of the variance in body mass index (BMI, kg/m(2)), fewer studies have used laboratory- based body composition measures. Moreover, comparable studies of human eating style are even more scarce. Advances in the laboratory measurement of human eating behavior may increase the yield of twin studies that solely focus on body composition.

Survival and induction of SOS in Escherichia coli treated with cisplatin, UV-irradiation, or mitomycin C are dependent on the function of the RecBC and RecFOR pathways of homologous recombination.

Resistance of tumors to drugs such as cisplatin and mitomycin C (MMC) is an important factor limiting their usefulness in cancer chemotherapy. The antitumor effects of these drugs are due to the formation of bifunctional adducts in DNA, with cisplatin causing predominantly intrastrand-crosslinks and MMC causing interstrand-crosslinks. The SOS chromotest was used to study the cellular mechanisms that process DNA damage in Escherichia coli exposed to cisplatin, ultraviolet irradiation (UV) and MMC and subsequently facilitate the production of a molecular signal for induction of the SOS response. Strains used in the SOS chromotest have a fusion of lacZ with the sfiA (sulA) gene so that the amount of SOS inducing signal, which is modulated by the ability of the cell to repair DNA, is measured by assaying beta-galactosidase activity. SOS induction in a strain proficient in homologous recombination (HR) was compared with that in isogenic strains deficient in HR due to a blocked RecBC pathway caused by a recB mutation or a blocked RecFOR pathway caused by a recO mutation. The effect of cisplatin treatment in a uvrA mutant strain blocked at the first step of NER was compared with that in an isogenic strain proficient in NER. Cellular resistance was measured as percent colony forming units (cfu) for cells treated with increasing doses of cisplatin, MMC and UV relative to that in untreated control cultures. The importance of both HR pathways for resistance to these treatments was demonstrated by decreased survival in mutants with the recB mutant being more sensitive than the recO mutant. SOS induction levels were elevated in the sensitive recB strain relative to the HR proficient strain possibly due to stalled and/or distorted replication forks at crosslinks in DNA. In contrast, induction of SOS was dependent on RecFOR activity that is thought to act at daughter strand gaps in newly synthesized DNA to mediate production of the signal for SOS induction. Proficiency in NER was necessary for both survival and high levels of SOS induction in cisplatin treated cells.

A family with a grand-maternally derived interstitial duplication of proximal 15q.

About 1% of individuals with autism or types of pervasive developmental disorder have a duplication of the 15q11-q13 region. These abnormalities can be detected by routine G-banded chromosome study, showing an extra marker chromosome, or demonstrated by fluorescence in situ hybridization (FISH) analysis, revealing an interstitial duplication. We report here the molecular, cytogenetic, clinical and neuropsychiatric evaluations of a family in whom 3 of 4 siblings inherited an interstitial duplication of 15q11-q13. This duplication was inherited from their mother who also had a maternally derived duplication. Affected family members had apraxia of speech, phonological awareness deficits, developmental language disorder, dyslexia, as well as limb apraxia but did not have any dysmorphic clinical features. The observations in this family suggest that the phenotypic manifestations of proximal 15q duplications may also involve language-based learning disabilities.

Uses of vitamins A, C, and E and related compounds in dermatology: a review.

Vitamins have been increasingly used as prophylactic and therapeutic agents in the management of skin disorders. The current literature is replete with studies that promote the potential benefits of these compounds and attempt to elucidate their mechanisms of action. We review the literature and discuss the roles, safety, and efficacy of vitamins A, C, and E and related compounds in cutaneous health and disease.

Cancer of the skin in the older patient.

This article focuses on the common precancers and skin cancers in the older patient. The hazards of ultraviolet radiation are explained briefly in relation to photoaging and the development of skin cancer. The etiology, clinical appearance, histopathologic diagnosis, treatment, and follow-up for each type of cancer are reviewed thoroughly. It is hoped that early recognition and treatment by geriatric physicians will have a positive impact on the reduction of the morbidity and mortality associated with these cancers in the elderly.