Opposing effects of ecdysone signaling regulate neuroblast proliferation to ensure coordination of brain and organism development.

Growth regulation must be robust to ensure correct final size, but also adaptative to adjust to less favorable environmental conditions. Developmental coordination between whole-organism and the brain is particularly important, as the brain is a critical organ with little adaptability. Brain growth mainly depends on neural stem cell (NSC) proliferation to generate differentiated neural cells, it is however unclear how organism developmental progression is coordinated with NSCs. Here we demonstrate that the steroid hormone ecdysone plays a multi-step, stage specific role in regulating Drosophila NSCs, the neuroblasts. We used animals that are unable to synthesize ecdysone, to show that the developmental milestone called "critical weight peak", the peak that informs the body has reached minimum viable weight to survive metamorphosis, acts a checkpoint necessary to set neuroblast cell cycle pace during larval neurogenesis. The peaks of ecdysone that occur post-critical weight are no longer required to maintain neuroblast division rate. We additionally show that in a second stage, at the onset of pupariation, ecdysone is instead required to trigger neuroblast's proliferation exit and consequently the end of neurogenesis. We demonstrate that, without this signal from ecdysone, neuroblasts lose their ability to exit proliferation. Interestingly, although these neuroblasts proliferate for a longer period, the number of differentiated neurons is smaller compared to wild-type brains, suggesting a role for ecdysone in neuron maintenance. Our study provides insights into how neural stem cells coordinate their division rate with the pace of body growth, identifying a novel coordination mechanism between animal development and NSC proliferation.

Interaction of the antifungal ketoconazole and its diphenylphosphine derivatives with lipid bilayers: Insights into their antifungal action.

Ketoconazole (Ke) is an important antifungal drug, and two of its diphenylphosphinemethyl derivatives (KeP: Ph2PCH2-Ke and KeOP: Ph2P(O)CH2-Ke) have shown improved antifungal activity, namely against a yeast strain lacking ergosterol, suggesting alternative modes of action for azole compounds. In this context, the interactions of these compounds with a model of the cell membrane were investigated, using POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) large unilamellar vesicles and taking advantage of the intrinsic fluorescence of Ke, KeP and KeOP. Steady-state fluorescence spectra and anisotropy, including partition and aggregation studies, as well as fluorescence lifetime measurements, were carried out. In addition, the ability of the compounds to increase membrane permeability was assessed through carboxyfluorescein leakage. The membrane/water mole fraction partition coefficients (Kp,x): (3.31 ± 0.36) x105, (8.31 ± 1.60) x105 and (4.66 ± 0.72) x106, for Ke, KeP and KeOP, respectively, show that all three compounds have moderate to high affinity for the lipid bilayer. Moreover, KeP, and particularly KeOP interact more efficiently with POPC bilayers than Ke, which correlates well with their in vitro antifungal activity. Furthermore, although the three compounds disturb the lipid bilayer, KeOP is the quickest and most efficient one. Hence, the higher affinity and ability to permeabilize the membrane of KeOP when compared to that of KeP, despite the higher lipophilicity of the latter, points to an important role of Ph2P(O)CH2- oxygen. Overall, this work suggests that membrane interactions are important for the antifungal activity of these azoles and should be considered in the design of new therapeutic agents.

Sleep timing behaviour, sleep duration and adherence to obesogenic dietary patterns from pre-school to school age: results from the Portuguese birth cohort Generation XXI.

In an obesogenic environment, short sleeping may increase opportunistic eating. The timing of sleep might also influence the drive to eat. This study investigated the prospective association of sleep timing and duration with diet in 5286 children from the Portuguese birth cohort Generation XXI, evaluated at 4 and 7 years of age. At 4 years, sleep duration was categorised into ≤10 and >10 h. Four sleep timing categories were generated based on the median split for sleep-onset and -offset times: 'Early Sleep-Early Wake'; 'Early Sleep-Late Wake'; 'Late Sleep-Early Wake'; 'Late Sleep-Late Wake'. At 7 years, diet was obtained by a food frequency questionnaire and three dietary patterns were included: 'Healthier', 'Energy-Dense Foods (EDF)' and 'Snacking'. The Healthy Eating Index was used to evaluate diet quality. Multinomial logistic regression models and generalised linear models were performed. Children who had a late sleep, independently of the time of waking up, had higher odds of following the 'EDF' pattern, compared with the 'Healthier'. Boys who had late sleep and/or late wake had also higher odds of following the 'Snacking' pattern and had poorer diet quality. In both sexes, a late sleep or late wake were associated with a lower diet quality, compared to the group 'Early Sleep-Early Wake', and independently of nap behaviour. In boys, shorter sleep duration was associated with a poorer diet. In conclusion, pre-schoolers with late bedtimes or wake-up times have worse dietary patterns and poorer diet quality at the age of 7 years, which seems to be independent of sleep duration.

Appetitive traits from childhood to adolescence: Analysis of their stability, derivation of trajectory profiles, and associated characteristics.

This study aimed to assess the potential stability of appetitive traits from childhood to early adolescence, identify groups of individuals with distinct trajectories for these traits, and explore their association with other child and family characteristics. Participants were 5040 children from the Generation XXI cohort. Appetitive traits were assessed with the Children's Eating Behaviour Questionnaire (CEBQ) at ages seven, 10, and 13 (eight subscales). Mixed-effect models estimated individual trajectories of appetitive traits and Gaussian mixture models identified groups following different trajectories (appetitive trait trajectory profiles). Appetitive traits showed moderate-to-high stability across the three ages (intra-class correlation coefficients:0.66-0.83); most of the variance observed across time were due to persistent individual differences rather than age-related changes. Six appetitive trait trajectory profiles were identified: 'Moderate appetite' (scores close to the average) (29% of children), 'Small to moderate appetite' (lowest food approach and emotional eating) (26%), 'Increasing appetite' (increasing food approach) (15%), 'Avid appetite' (highest food approach and lowest food avoidance) (12%), 'Smallest appetite' (highest food avoidance and low food approach) (10%), and 'Small appetite but increasing' (decreasing high food avoidance and Desire to Drink) (8%). In multinomial logistic regression, these profiles were associated with different child and family characteristics. Compared to children with a 'Moderate appetite' profile, those with higher BMI, who desired a thinner body, whose mothers were younger, had lower education, higher pre-pregnancy BMI (OR = 1.07; 95%CI:1.04,1.09), smoked during pregnancy (OR = 1.51; 95%CI:1.21,1.90), and used more restrictive feeding practices (OR = 1.79; 95%CI:1.57,2.03) had increased odds of belonging to the 'Avid Appetite'. In conclusion, distinct appetitive trait trajectory profiles emerged, differentiating individuals with avid and small appetites. These findings have implications for identifying children at higher risk for obesogenic profiles.

Sleep duration is associated with appetitive traits in school-age years - results from the Generation XXI birth cohort.

Sleep may influence appetite regulation through physiological and neurocognitive pathways. However, the association between sleep and appetite in childhood has been scarcely reported, particularly using a prospective design. We aimed to test associations between sleep duration at 7 years of age (y) and appetitive traits at both 7 and 10 y. Participants are from the population-based birth cohort Generation XXI (Porto, Portugal), at 7 (n = 2437) and 10 y (n = 1938) follow-ups. Data on sleep was gathered at 7 y and, considering bedtime and get-up time, total mean sleep duration was calculated and further categorized according to the 10th and 90th percentiles. Appetitive traits were assessed at 7 and 10 y using the parent-reported Children's Eating Behaviour Questionnaire. Associations were tested through Generalized Linear Models (co-variates: child's sex; maternal age, education and pre-pregnancy body mass index at 7 y). At 10 y, associations were further adjusted for the respective appetitive trait at 7 y. Children slept a mean of 10.2 h/night, and 13% and 9% slept ≤9.5 and ≥ 11.0 h/night at 7 y, respectively. For each additional hour in sleep duration, children scored 0.078 (99%CI: -0.145; -0.011) lower on Food Responsiveness, 0.065 (99%CI: -0.129; -0.002) lower on Emotional Undereating and 0.096 (99%CI: -0.161; -0.032) lower on Food Fussiness. Lastly, children sleeping ≤9.5 h/night scored higher on Food Responsiveness (ß = 0.145 99%CI: 0.020; 0.271); while those sleeping ≥11.0 h/night scored lower on Food Fussiness (ß = -0.255 99%CI: -0.370; -0.079). No significant prospective associations were found. In conclusion, in 7 y children, sleep duration was cross-sectionally associated with lower scores on food approach (Food Responsiveness) and avoidant traits (Emotional Undereating and Food Fussiness). However, the magnitude of the associations was small and further studies are warranted.

Antibacterial and Antileishmanial Activity of 1,4-Dihydropyridine Derivatives.

: We have synthesized twenty-three 1,4-dihydropyridine derivatives (1,4-DHPs) by using a microwave-assisted one-pot multicomponent Hantzsch reaction and evaluated their antibacterial activity against a representative panel of cariogenic bacteria and their in vitro antileishmanial activity against Leishmania (L.) amazonensis promastigotes and amastigotes. Thirteen compounds were moderately active against Streptococcus sanguinis, Streptococcus mitis, and Lactobacillus paracasei. Compound 22 (diethyl 4-(3-methoxy-4-hydroxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) displayed moderate antibacterial activity against S. mitis and S. sanguinis, with a Minimum Inhibitory Concentration (MIC) of 500 µg/mL); compounds 8 (ethyl 2,7,7-trimethyl-4-(3-chlorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) and 10 (ethyl 2,7,7-trimethyl-4-(3-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) were moderately active against S. sanguinis (MIC = 500 µg/mL) and very active against L. amazonensis promastigotes (IC50 = 43.08 and 34.28 µM, respectively). Among the eight 1,4-DHPs that were active (IC50 < 50 µM) against L. amazonensis promastigotes, compound 13 (ethyl 2,7,7-trimethyl-4-(3,4,5-trimethoxyphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) was the most active (IC50 = 24.62 µM) and had a Selectivity Index (SI) higher than 4 compared to GM07492A cells. On the other hand, compound 9 (ethyl 2,7,7-trimethyl-4-(2-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) was the most active against L. amazonensis amastigotes (IC50 = 16.27 µM and SI = 6.1) after 24 h of treatment. Based on our results, asymmetric 1,4-DHPs derived from dimedone exhibit antileishmanial potential.

Adolescents' Perceptions About Healthy and Sustainable Diets: A Qualitative School-Based Study in Portugal.

In this qualitative study, we explored Portuguese adolescents' perceptions of diet, sustainability, and health through six focus group discussions (FGDs). Fifty-five adolescents (10-18 years) participated. FGDs focused on sustainability in food choices and its health impact, with our primary interest in their perceptions. Results showed a limited comprehension of "sustainable/sustainability," especially among younger participants. Those aware of sustainability recognized its diverse aspects, including health, economic, and ecological domains. Some adolescents recognized the link between health and sustainability in their diets, emphasizing the need for food literacy. These findings emphasize the importance of public health and sustainable policies among Portuguese adolescents.

Weight trajectories from birth to 5 years and child appetitive traits at 7 years of age: a prospective birth cohort study.

Rapid prenatal and postnatal weight gain seem to alter appetite regulation and hypothalamic functions through different pathways; however, little is known on how early life growth trajectories may influence appetitive traits in school-age. We aimed to explore the associations between weight trajectories from birth to 5 years and appetitive traits at 7. Participants were from the Generation XXI birth cohort (n 3855). Four weight trajectories were investigated: 'normal weight gain' (closely overlaps the 50th percentile in the weight-for-age curve), 'weight gain during infancy' (low birth weight and weight gain mainly during infancy), 'weight gain during childhood' (continuous weight gain since birth) and 'persistent weight gain' (always showing higher weight than the average). Appetitive traits were assessed through the Children's Eating Behaviour Questionnaire. Associations were tested using generalised linear models, adjusted for maternal and child characteristics. Compared with 'normal weight gain', those in the other growth trajectories showed greater enjoyment of food and eating in response to food stimuli (i.e. Food Responsiveness) but were less able to compensate for prior food intake and ate faster at 7 (i.e. less Satiety Responsiveness and Slowness in Eating). Also, those with 'weight gain during infancy' showed to have greater Emotional Overeating and less Emotional Undereating and were fussier. Associations were stronger if greater weight gain occurred during infancy. Early infancy seems to be a sensitive period in the development of later appetitive traits. The control of rapid growth during infancy, besides strategies focused on the overall environment where children are living, is necessary.

Associations between children's reports of food insecurity and dietary patterns: findings from the Generation XXI birth cohort.

Evidence on the association between children's food insecurity (FI) and dietary patterns (DPs) is scarce. This study assessed the association between children's FI and a priori and a posteriori-defined DPs in a Portuguese population-based sample of children. A cross-sectional study including 2800 children from the 10-year-old follow-up of the Generation XXI birth cohort was performed. Data on food security status, assessed by the Self-administered Food Security Survey Module for children (SAFSSMC), dietary intake and socio-demographics were collected. A previously developed Healthy Eating Index (HEI) was adapted for this study. Using the HEI score and its food groups, linear and logistic regression models were performed. Using latent class analysis, five a posteriori-defined DPs were identified. The DPs names considered an overall picture of the DP. Food security status as a categorical (food security/FI) and continuous variable (SAFSSMC raw score: higher scores representing higher FI) was used. Multinomial logistic regression models were used to assess the association between food security status and DPs. Children's FI (9·4 %) was inversely associated with the HEI score (ß=-0·695;95%CI:-1·154,-0·235), representing worse diet quality. A higher SAFSSMC raw score was associated with low fruit and vegetables (OR=1·089;95%CI:1·023,1·159) and seafood and eggs consumption (OR=1·073;95%CI:1·009,1·142) and high consumption of meat and meat products (OR=1·091;95%CI:1·026,1·160), salty snacks (OR=1·067;95%CI:1·003,1·136) and soft drinks (OR=1·097;95%CI:1·031,1·168). The SAFSSMC raw score was positively associated with 'Low consumption' (OR=1·119;95%CI:1·016,1·232), 'Energy-dense foods' (OR=1·155;95%CI:1·028,1·298) and 'Snacking' (OR=1·119;95%CI:1·006,1·245) DPs. FI was associated with worse dietary choices. Intervention strategies targeting food insecure children should be developed to promote healthy dietary habits.

Early life exposures are associated with appetitive traits in infancy: findings from the BiTwin cohort.

PURPOSE: To determine the stability of appetitive traits during infancy and their association with early life exposures. METHODS: Participants were from the BiTwin birth cohort (longitudinal study of Portuguese infants). Appetitive traits at 3 months were measured using the Baby Eating Behaviour Questionnaire (n = 347) and at 12 months with the Children's Eating Behaviour Questionnaire for toddlers (n = 325). Stability was assessed with multi-level models. The association of early life exposures (weight for gestational age, mode of feeding, prematurity, smoking during pregnancy, maternal pre-pregnancy BMI, gestational weight gain, and diabetes mellitus diagnosis) with infant appetitive traits was estimated by multivariable linear regression models. RESULTS: Appetite traits showed limited stability (ICCs: 0.25-0.34). Associations with early life exposures varied by age. At 3 months, infants of mothers with higher pre-pregnancy BMI and excessive gestational weight gain had low Satiety Responsiveness. In contrast, infants small for gestational age scored high in this trait (ß̂ = 0.241; 95% CI 0.056-0.425). Exclusively formula-fed infants presented weak food approach traits at this age, namely low Enjoyment of Food (ß̂ = - 0.145; 95% CI - 0.270 to - 0.019) and Food Responsiveness (ß̂ = - 0.415; 95% CI - 0.618 to - 0.212). At 12 months, infants who were small for gestational age had low Food Responsiveness (ß̂ = - 0.297; 95% CI - 0.523 to - 0.072), in contrast, infants of mothers who gained excessive gestational weight had high scores in this trait. Formula feeding was related to rapid eating (Slowness in Eating: ß̂ = - 0.252; 95% CI 0.451 to - 0.054). CONCLUSION: Early life exposures may play a role in the development of infants' appetitive traits, which then change during the first year of life. Interventions focussed on maternal and infant health may have the potential to shape appetite in infancy.

Anti-inflammatory effects of naringenin 8-sulphonate from Parinari excelsa Sabine stem bark and its semi-synthetic derivatives.

The inflammatory response is a vital mechanism for repairing damage induced by aberrant health states or external insults; however, persistent activation can be linked to numerous chronic diseases. The nuclear factor kappa ß (NF-κB) inflammatory pathway and its associated mediators have emerged as critical targets for therapeutic interventions aimed at modulating inflammation, necessitating ongoing drug development. Previous studies have reported the inhibitory effect of a hydroethanol extract derived from Parinari excelsa Sabine (Chrysobalanaceae) on tumour necrosis factor-alpha (TNF-α), but the phytoconstituents and mechanisms of action remained elusive. The primary objective of this study was to elucidate the phytochemical composition of P. excelsa stem bark and its role in the mechanisms underpinning its biological activity. Two compounds were detected via HPLC-DAD-ESI(Ion Trap)-MS2 analysis. The predominant compound was isolated and identified as naringenin-8-sulphonate (1), while the identity of the second compound (compound 2) could not be determined. Both compound 1 and the extract were assessed for anti-inflammatory properties using a cell-based inflammation model, in which THP-1-derived macrophages were stimulated with LPS to examine the treatments' effects on various stages of the NF-κB pathway. Compound 1, whose biological activity is reported here for the first time, demonstrated inhibition of NF-κB activity, reduction in interleukin 6 (IL-6), TNF-α, and interleukin 1 beta (IL-1ß) production, as well as a decrease in p65 nuclear translocation in THP-1 cells, thus highlighting the potential role of sulphur substituents in the activity of naringenin (3). To explore the influence of sulphation on the anti-inflammatory properties of naringenin derivatives, we synthesized naringenin-4'-O-sulphate (4) and naringenin-7-O-sulphate (5) and evaluated their anti-inflammatory effects. Naringenin derivatives 4 and 5 did not display potent anti-inflammatory activities; however, compound 4 reduced IL-1ß production, and compound 5 diminished p65 translocation, with both exhibiting the capacity to inhibit TNF-α and IL-6 production. Collectively, the findings demonstrated that the P. excelsa extract was more efficacious than all tested compounds, while providing insights into the role of sulphation in the anti-inflammatory activity of naringenin derivatives.

Parental child-feeding practices at 4 years of age are associated with dietary patterns of 7-year-olds.

BACKGROUND: Parental child-feeding practices have been associated with child body mass index (BMI) and specific food group consumption; however, their role in the development of dietary patterns is less understood. We aim to study the association between parental child-feeding practices at 4 years old and dietary patterns at 7 years that explain BMI z-scores at age 10. METHODS: Participants were children from the Generation XXI birth cohort (n = 3272). Three patterns of feeding practices at 4 years were previously identified: 'Perceived monitoring', 'Restriction' and 'Pressure to eat'. At 7 years, two dietary patterns were derived: 'Energy-dense foods', higher consumption of energy-dense foods and drinks and processed meats and lower consumption of vegetable soup (significantly associated with BMI z-scores at 10 years) and 'Fish-based', higher in fishery intake and lower in energy-dense food intake. Associations were estimated by linear regression models, adjusted for potential confounders (mother's age, education and pre-pregnancy BMI). RESULTS: Girls whose parents used more Restriction, Perceived monitoring and Pressure to eat at 4 years were less likely to follow the 'Energy-dense foods' dietary pattern at 7 years (ß̂ = -0.082; 95% confidence intervals [CI]: -0.134; -0.029; ß̂ = -0.093; 95% CI: -0.146; -0.039; ß̂ = -0.079; 95% CI: -0.135; -0.04, respectively). In both sexes, children whose parents used more Restriction and Perceived monitoring at 4 years were more likely to follow the 'Fish-based' dietary pattern at 7 years (girls: ß̂ = 0.143; 95% CI: 0.077; 0.210; ß̂ = 0.079; 95% CI: 0.011; 0.148; boys: ß̂ = 0.157; 95% CI: 0.090; 0.224; ß̂ = 0.104; 95% CI: 0.041; 0.168). CONCLUSIONS: Children whose parents used more Restriction and Perceived monitoring at preschool age were more likely to follow healthier dietary patterns at age 7.

Clinical and epidemiological aspects of Delta and Gamma SARS-CoV-2 variant of concern from the western Brazilian Amazon.

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has become a major concern contributing to increased morbidity and mortality worldwide. OBJECTIVES: Here we describe the replacement of the Gamma variant of concern (VOC) with Delta in the western Brazilian Amazon. METHODS: In this study, we analysed 540 SARS-CoV-2 positive samples determined by qualitative real-time RT-PCR selected in the state of Rondônia between June and December 2021. The positive cohort was sequenced through next-generation sequencing (NGS) and each sample was quantified using real-time RT-qPCR, the whole genome sequence was obtained, SARS-CoV-2 lineages were classified using the system Pango and the maximum likelihood (ML) method was used to conduct phylogenetic analyses. FINDINGS: A total of 540 high-quality genomes were obtained, where the Delta VOC showed the highest prevalence making up 72%, with strain AY.43 being the most abundant, while the Gamma VOC was present in 28%, where the P.1 strain was the most frequent. In this study population, only 32.96% (178/540) had completed the vaccination schedule. MAIN CONCLUSIONS: This study highlighted the presence of Gamma and Delta variants of SARS-CoV-2 in RO. Furthermore, we observed the replacement of the Gamma VOC with the Delta VOC and its lineages.

Downregulation of Sirtuin 1 Does Not Account for the Impaired Long-Term Potentiation in the Prefrontal Cortex of Female APPswe/PS1dE9 Mice Modelling Alzheimer's Disease.

Alzheimer's disease (AD), which predominantly affects women, involves at its onset a metabolic deregulation associated with a synaptic failure. Here, we performed a behavioral, neurophysiological and neurochemical characterization of 9-month-old female APPswe/PS1dE9 (APP/PS1) mice as a model of early AD. These animals showed learning and memory deficits in the Morris water maze, increased thigmotaxis and anxiety-like behavior and showed signs of fear generalization. Long-term potentiation (LTP) was decreased in the prefrontal cortex (PFC), but not in the CA1 hippocampus or amygdala. This was associated with a decreased density of sirtuin-1 in cerebrocortical synaptosomes and a decreased density of sirtuin-1 and sestrin-2 in total cerebrocortical extracts, without alterations of sirtuin-3 levels or of synaptic markers (syntaxin, synaptophysin, SNAP25, PSD95). However, activation of sirtuin-1 did not affect or recover PFC-LTP deficit in APP/PS1 female mice; instead, inhibition of sirtuin-1 increased PFC-LTP magnitude. It is concluded that mood and memory dysfunction in 9-month-old female APP/PS1 mice is associated with a parallel decrease in synaptic plasticity and in synaptic sirtuin-1 levels in the prefrontal cortex, although sirtiun1 activation failed to restore abnormal cortical plasticity.

Appetitive traits and food groups consumption in school-aged children: prospective associations from the Generation XXI birth cohort.

PURPOSE: Appetite can influence children's dietary choices; however, this relationship in school-aged children is still unclear. We aimed to explore the prospective associations between child appetitive traits at age 7 and food consumption at 10 years of age. METHODS: The study included 3860 children from the Generation XXI birth cohort, recruited in 2005/2006 in Porto, Portugal. The Children's Eating Behaviour Questionnaire was used to evaluate children's appetitive traits at 7 years. Food consumption was measured at 10 years through a validated Food Frequency Questionnaire. Logistic regression models were performed and adjusted for possible confounders. RESULTS: Children with greater Enjoyment of Food at 7 years were 36% more likely to eat fruits ≥ 2 times/day and 54% more likely to eat vegetables > 2.5 times/day at 10 years compared to those with less frequent consumption. Children who ate more in response to negative emotions had higher odds of consuming energy-dense foods (OR = 1.33; 99% CI 1.13-1.58) and salty snacks (OR = 1.28; 99% CI 1.08-1.51) 3 years later. Those with less ability to adjust intake (higher Satiety Responsiveness) and more selective about foods (higher Food Fussiness) at 7 years were less likely to consume vegetables frequently, and were more likely to consume energy-dense foods and sugar-sweetened beverages. CONCLUSIONS: Children's appetitive traits at 7 years were associated with the consumption of several food groups at 10 years of age. Eating more in response to negative emotions (Emotional Eating), with less ability to adjust intake (Satiety Responsiveness) and more food selectivity (Food Fussiness) were associated with worse dietary choices (in general, lower fruit and vegetables, and higher energy-dense foods and sugar-sweetened beverages consumption). LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies.

Integrating animal development: How hormones and metabolism regulate developmental transitions and brain formation.

Our current knowledge on how individual tissues or organs are formed during animal development is considerable. However, the development of each organ does not occur in isolation and thus their formation needs to be done in a coordinated manner. This coordination is regulated by hormones, systemic signals that instruct the simultaneous development of all organs and direct tissue specific developmental programs. In addition, multi- and individual-organ development requires the integration of the nutritional state of the animal, since this affects nutrient availability necessary for the progression of development and growth. Variations in the nutritional state of the animal are normal during development, as the sources and access to nutrients greatly differ depending on the animal stage. Furthermore, adversities of the external environment also exert major alterations in extrinsic nutritional conditions. Thus, both in normal and malnutrition circumstances, the animal needs to trigger metabolic changes to maintain energy homeostasis and sustain growth and development. This metabolic flexibility is mediated by hormones, that drive both developmental encoded metabolic transitions throughout development and adaptation responses according to the nutritional state of the animal. This review aims to provide a comprehensive summary of the current knowledge of how endocrine regulation coordinates multi-organ development by orchestrating metabolic transitions and how it integrates metabolic adaptation responses to starvation. We also focus on the particular case of brain development, as it is extremely sensitive to hormonally induced metabolic changes. Finally, we discuss how brain development is prioritized over the development of other organs, as its growth can be spared from nutrient deprivation.

Maternal perception, concern and dissatisfaction with child weight and their association with feeding practices in the Generation XXI birth cohort.

What a mother thinks about her child's weight status might influence what and how she feeds her child. We examined the association between maternal perception, concern and dissatisfaction with child weight alongside feeding practices. Participants were from the Generation XXI birth cohort (n = 3233). A validated version of the Child Feeding Questionnaire and the Overt/Covert Control scale were used. Associations were evaluated by linear regression models (ß coefficients and 95 % confidence intervals (95 % CI) with Bonferroni correction). Perceived underweight was associated with practices promoting food intake, such as higher pressure to eat at ages 4 and 7 years (ß = 0·229; 95 % CI: 0·059, 0·398 and ß = 0·190; 95 % CI:0·005, 0·376, respectively) and lower restriction at age 4 (ß = -0·175; 95 % CI: -0·0310, -0·039). At age 7, perceived overweight was associated with higher covert control (ß = 0·203; 95 % CI: 0·029, 0·376). Mothers who were concerned about child weight reported higher restriction (ß = 0·226; 95 % CI: 0·142, 0·310 at 4 years and ß = 0·261; 95 % CI: 0·169, 0·353 at 7 years) and covert control (ß = 0·183; 95 % CI: 0·083, 0·282 at 4 years and ß = 0·171; 95 % CI: 0·073, 0·269 at 7 years). Maternal desire for a heavier child was associated with higher pressure to eat at both ages (ß = 0·285; 95 % CI: 0·163, 0·406 and ß = 0·393; 95 % CI: 0·266, 0·520), while the desire for a thinner child was related to higher covert control at 7 years of age (ß = 0·158; 95 % CI: 0·001, 0·316). Maternal perceptions and concern for child weight status are associated with feeding practices independently of actual weight status.

Appetitive behaviors and body composition in school-age years: Bi-directional analyses in a population-based birth cohort.

Cross-sectional studies have consistently associated appetitive behaviors with child body mass index. However, few prospective studies have investigated the association between appetite and other measures of body composition and its directionality. We aimed to investigate the bi-directional relationship between appetitive behaviors and body composition in school-aged children. Data from 3668 children of the Generation XXI birth cohort were analyzed. Appetitive behaviors were assessed at 7 and 10 years through the Children's Eating Behavior Questionnaire. Higher fat mass and fat-free mass were measured through tetrapolar bioelectric impedance and waist-to-weight and waist-to-height ratios were calculated. Fat and fat-free mass indexes, waist-to-weight and waist-to-height age- and sex-specific z-scores were then calculated. Cross-lagged analyses were performed (body composition at 7 to appetitive behaviors at 10 and the reverse) to measure the magnitude and direction of associations. Fat mass and waist-to-height ratio at 7y predicted greater food approach behaviors at 10y (Enjoyment of Food, Food Responsiveness, Desire to Drink and Emotional Overeating), but not waist-to-weight, which seems to be consequence of child's avid appetite (e.g. Enjoyment of Food at 7y: ßstandardized = 0.085, 95%CI = 0.041; 0.128, p < 0.001). Child scores on food avoidant behaviors, such as Satiety Responsiveness (ßstandardized = -0.073, 95%CI = -0.110;-0.034, p < 0.001) and Slowness in Eating (ßstandardized = -0.080, 95% CI = -0.120;-0.041, p < 0.001) at 7y predicted lower fat-free mass at 10. Appetitive behaviors may not solely predict weight status, but the path of association between body composition and later appetitive behavior may also be true, especially for food approaching behaviors and adipose tissue. Interventions aiming to prevent excess weight should focus on appetitive behaviors. Moreover, in children with higher adiposity, other pathways also seem to regulate appetite and need to be considered in interventions.

Association of early feeding practices with dietary patterns of 7-year-olds from the birth cohort Generation XXI.

Early feeding practices have been related to child's body mass index (BMI), however, their role in establishing dietary patterns is less well understood. The aim of this study was to examine the association of parent-reported early feeding practices (breastfeeding duration, type of foods and timing of complementary feeding) and dietary patterns identified at age 7 to explain BMI z-scores at 10 years of age. Participants were children from the Generation XXI cohort, evaluated at 4, 7 and 10 years of age (n = 3673). At 7 years-old, dietary intake was assessed with a validated food-frequency questionnaire. Two dietary patterns were previously derived: "Energy-dense foods" (higher in energy-dense foods, and lower in vegetable soup, significantly associated with BMI z-score at 10 years-old, and the "Fish-based" dietary pattern (higher in fish consumption and low in energy-dense foods). Adjusted sex-stratified associations were estimated by generalized linear models. Boys and girls who were never breastfed or were breastfed for a very short duration had lower scores in the "Fish-based" dietary pattern, compared to those with longer breastfeeding durations (Boys: ß = -0.219; 95%CI: 0.361; -0.077; Girls: ß = -0.223; 95%CI: 0.358; -0.088). No significant associations between breastfeeding and the "Energy-dense foods" dietary pattern were found. Boys and girls who were offered cereals as a first food during complementary feeding, in comparison with soup, presented lower scores in the "Energy-dense foods" dietary pattern (Boys: ß = -0.183; 95%CI: 0.292; -0.074; Girls: ß = -0.155; 95%CI: 0.259; -0.050), but only girls presented higher scores in the 'Fish-based' dietary pattern (ß = 0.137; 95%CI: 0.006; 0.267). The age of introduction of complementary feeding was not significantly associated with the dietary patterns. Parents should be supported in their infant feeding decisions, given the potential effects of breastfeeding duration and first foods at complementary feeding on shaping longer term dietary patterns of young children.

Longitudinal bidirectional relationship between children's appetite and diet quality: A prospective cohort study.

This study explored the relationship between eating behaviours and diet quality, from 7 to 10y. The sample included 3879 children evaluated, from the Portuguese birth cohort Generation XXI, with complete information on Food Frequency Questionnaire (FFQ) and the Children Eating Behaviour Questionnaire (CEBQ). A healthy eating index (HEI) (range: 9-31) was developed to evaluate the child's diet quality. The eight CEBQ's eating behaviours were included in the analysis. Generalised linear models were used to estimate the associations. Adjusted structural equation modelling was performed to study the direction of the associations. Eating behaviours measured at age 7y tracked to age 10y. A bidirectional inverse association between the food fussiness trait and diet quality was found, with a similar magnitude (p < 0.001), thus a higher score on food fussiness predicted a lower quality of the diet. A higher HEI score at 7y was associated with lower satiety responsiveness at 10y (ßstandardized = -0.039), and a higher HEI score at age 10y was associated with higher enjoyment of food at 7y (ßstandardized = 0.046). Eating behaviours were linked to diet quality in children with high enjoyment of food and low food fussiness at age 7y linked to a high-quality diet at 10y. In addition, children with high-quality diets at 7y were more likely to have lower food fussiness and satiety responsiveness at 10y. Given the stability of eating behaviours and the bidirectional nature of effects between eating behaviours and dietary quality in the long term, tailored interventions may be needed to encourage the acquisition of healthy eating behaviours and habits in early life.