Caloric compensation in preschool children: relationships with body mass and differences by food category

Maintaining a healthy weight may involve compensating for previously consumed calories at subsequent meals. To test whether heavier children demonstrated poorer caloric compensation across a range of conditions, and to explore whether compensation failure was the result of inadequate adjustment of overall intake or specific over-consumption of highly palatable, high energy-density 'junk' foods, we administered two compensation tests to a sample of 4-5 y olds. For Test A, preloads varied only in carbohydrate content and were organoleptically indistinguishable (200 ml orange-flavored beverage [0 kcal vs. 200 kcal]). For Test B, the preloads varied substantially in both macronutrient composition and learned gustatory cues to caloric content (200 ml water [0 kcal] vs. 200 ml strawberry milkshake [200 kcal]). Each preload was followed 30 min later by a multi-item ad-libitum meal containing junk foods (chocolate cookies, cheese-flavored crackers) and core foods (fruits and vegetables, bread rolls, protein foods). Testing took place at the children's own school under normal lunch-time conditions. Children were weighed and measured. Caloric compensation occurred in both tests, in terms of total, junk and core food intake (RMANOVA, all p < 0.01). Higher BMI z scores were associated with greater average caloric compensation (r = -0.26p < 0.05), such that overweight/obese children showed least compensation (41%), children over the 50th centile the next least (59%), and children under the 50th centile (80%) the most. For Test A only, obese/overweight children compensated less well than normal weight children in terms of junk food intake (RMANOVA preload-by-weight group interaction p < 0.05), with no significant effect for core foods. Our results suggest that caloric compensation is consistently poorer in heavier children, and that overweight/obese children's preferences for junk foods may overwhelm intake regulation mechanisms within meals containing those foods. (C) 2017 Elsevier Ltd. All rights reserved.National Institute of Diabetes and Ingestive and Kidney Diseases (NIDDK)Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Office of the Director, National Institutes of Health (OD)Coordenação de Aperfeiçoamento de Pessoal de Níel Superior (CAPES)Medical Research Council (MRC)Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Child & Adolescent Psychiat, 600 N Wolfe St Phipps 300, Baltimore, MD 21287 USAUniv Roehampton, Dept Psychol, London, EnglandFed Univ São Paulo UNIFESP, Dept Pediat, Discipline Nutrol, São Paulo, SP, BrazilFed Univ São Paulo UNIFESP, Dept Pediat, Discipline Nutrol, São Paulo, SP, BrazilNIDDK: R00DK088360OD: U54HD070725Web of Scienc

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Resting state functional connectivity of loss of control eating and weight concern in youth

Eating disorders (EDs) are difficult to treat and understanding the etiology of symptoms of the disease, including neural correlates, can aid in uncovering early risk factors to target for disease prevention. Loss of control (LOC) eating that accompanies binge eating in individuals with bulimia nervosa (BN) or binge eating disorder (BED), and the over-concern with weight and shape (WC), a characteristic of individuals with anorexia nervosa (AN) and BN, are two symptoms that often predict later development of EDs. In this study we examine fMRI resting state functional connectivity in individuals from a population sample (ages 10-20 years) with LOC (n =39), WC (n=43) and with both LOC and WC (n =37), compared to controls (n =36), to uncover differential brain networks underlying these symptoms. Results showed that individuals with LOC eating had decreased connectivity of executive control regions to regions related to self-processing, and individuals with WC had decreased connectivity within sensory regions, and between somatosensory to visual processing regions. The group with both LOC and WC had decreased connectivity within sensory and reward regions, and between reward regions to visual and attentional processing regions, as well as increased connectivity between an inhibitory control region to sensory regions. Results suggest altered brain connectivity is related to ED symptoms even in the absence of ED diagnosis, and because the results were in a young sample these disruptions are likely early neurological markers prior to onset of disease.M.S., Psychology -- Drexel University, 201

Amodal Brain Activation and Functional Connectivity in Response to High-Energy-Density Food Cues in Obesity

OBJECTIVE: The obesogenic environment is pervasive, yet only some people become obese. We aimed to investigate whether obese individuals show differential neural responses to visual and auditory food cues, independent of cue modality. DESIGN AND METHODS: Obese (BMI 29;-41, n=10) and lean (BMI 20-24, n=10) females underwent fMRI scanning during presentation of auditory (spoken word) and visual (photograph) cues representing high energy-density [ED] and low-ED foods. We examined the effect of obesity on whole brain activation, and on functional connectivity with the midbrain/VTA. RESULTS: Obese compared with lean women showed greater modality-independent activation of the midbrain/VTA and putamen in response to high-ED (vs. low-ED) cues, as well as relatively greater functional connectivity between the midbrain/VTA and cerebellum (p<0.05 corrected). CONCLUSIONS: Heightened modality-independent responses to food cues within the midbrain/VTA and putamen, and altered functional connectivity between the midbrain/VTA and cerebellum, could contribute to excessive food intake in obese individuals

Greater Anterior Cingulate Activation and Connectivity in Response to Visual and Auditory High-Calorie Food Cues in Binge Eating: Preliminary Findings

Obese individuals show altered neural responses to high-calorie food cues. Individuals with binge eating [BE], who exhibit heightened impulsivity and emotionality, may show a related but distinct pattern of irregular neural responses. However, few neuroimaging studies have compared BE and non-BE groups. To examine neural responses to food cues in BE, 10 women with BE and 10 women without BE (non-BE) who were matched for obesity (5 obese and 5 lean in each group) underwent fMRI scanning during presentation of visual (picture) and auditory (spoken word) cues representing high energy density (ED) foods, low-ED foods, and non-foods. We then compared regional brain activation in BE vs. non-BE groups for high-ED vs. low-ED foods. To explore differences in functional connectivity, we also compared psychophysiologic interactions [PPI] with dorsal anterior cingulate cortex [dACC] for BE vs. non-BE groups. Region of interest (ROI) analyses revealed that the BE group showed more activation than the non-BE group in the dACC, with no activation differences in the striatum or OFC. Exploratory PPI analyses revealed a trend towards greater functional connectivity with dACC in the insula, cerebellum, and supramarginal gyrus in the BE vs. non-BE group. Our results suggest that women with BE show hyper-responsivity in the dACC as well as increased coupling with other brain regions when presented with high-ED cues. These differences are independent of body weight, and appear to be associated with the BE phenotype

Cortical Control of Adaptive Locomotion in Wild-Type Mice and Mutant Mice Lacking the Ephrin-Eph Effector Protein α2-Chimaerin

In voluntary control, supraspinal motor systems select the appropriate response and plan movement mechanics to match task constraints. Spinal circuits translate supraspinal drive into action. We studied the interplay between motor cortex (M1) and spinal circuits during voluntary movements in wild-type (WT) mice and mice lacking the α2-chimaerin gene (Chn1−/−), necessary for ephrinB3-EphA4 signaling. Chn1−/− mice have aberrant bilateral corticospinal systems, aberrant bilateral-projecting spinal interneurons, and disordered voluntary control because they express a hopping gait, which may be akin to mirror movements. We addressed three issues. First, we determined the role of the corticospinal system in adaptive control. We trained mice to step over obstacles during treadmill locomotion. We compared performance before and after bilateral M1 ablation. WT mice adaptively modified their trajectory to step over obstacles, and M1 ablation increased substantially the incidence of errant steps over the obstacle. Chn1−/− mice randomly stepped or hopped during unobstructed locomotion but hopped over the obstacle. Bilateral M1 ablation eliminated this obstacle-dependent hop selection and increased forelimb obstacle contact errors. Second, we characterized the laterality of corticospinal action in Chn1−/− mice using pseudorabies virus retrograde transneuronal transport and intracortical microstimulation. We showed bilateral connections between M1 and forelimb muscles in Chn1−/− and unilateral connections in WT mice. Third, in Chn1−/− mice, we studied adaptive responses before and after unilateral M1 ablation. We identified a more important role for contralateral than ipsilateral M1 in hopping over the obstacle. Our findings suggest an important role for M1 in the mouse in moment-to-moment adaptive control, and further, using Chn1−/− mice, a role in mediating task-dependent selection of mirror-like hopping movements over the obstacle. Our findings also stress the importance of subcortical control during adaptive locomotion because key features of the trajectory remained largely intact after M1 ablation

Patterns of body weight change affect weight loss during a multidisciplinary intervention in adolescents with obesity

International audienceAim: The current pediatric obesity health challenge necessitates a better understanding of the factors affecting weight loss success during interventions. The aim of this observational study was to test the impact of the rate of initial weight loss and body weight variability on weight loss during a 9-month residential, multidisciplinary weight loss program in adolescents with obesity. Methods: This retrospective study considered a whole sample of 510 adolescents with obesity (12-16 years, 435 girls). Body weight assessment was performed before (T0) and each week during the 9 months of a multidisci-plinary weight loss program. Initial weight change (week 4-W4) and overall weight change at week 12 (T1) and the end of the intervention (T2) were considered. Participants were divided into three groups (tertiles), based on their percentage of weight loss between T0 and W4; and weight variability was expressed by the root mean square error (RMSE) around each participant's regression line at each considered period (W4, T1, T2). Results: Adolescents with lower initial weight loss at W4 (tertile 3) displayed the lesser weight loss at T1 and T2 compared with adolescents in tertile 1 and 2. The RMSE was positively associated with the percentage of weight loss of the period considered, but when the analyses were adjusted for age and initial body weight, there was no more significant association.Conclusions: The rate of weight loss during the first few weeks is crucial for weight loss success, and weight variability is positively associated with weight loss in adolescents with obesity. Overall, results show that initial body weight is a determinant characteristic to consider during a lifestyle intervention. Further studies are thus needed to better understand the relationship between body weight change patterns and weight loss during the dynamic state that is adolescence

Total ad libitum meal intake by binge eating sub-group and condition.

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