Emerging Roles of Small Extracellular Vesicles in Gastrointestinal Cancer Research and Therapy.

Discovered in the late eighties, sEVs are small extracellular nanovesicles (30-150 nm diameter) that gained increasing attention due to their profound roles in cancer, immunology, and therapeutic approaches. They were initially described as cellular waste bins; however, in recent years, sEVs have become known as important mediators of intercellular communication. They are secreted from cells in substantial amounts and exert their influence on recipient cells by signaling through cell surface receptors or transferring cargos, such as proteins, RNAs, miRNAs, or lipids. A key role of sEVs in cancer is immune modulation, as well as pro-invasive signaling and formation of pre-metastatic niches. sEVs are ideal biomarker platforms, and can be engineered as drug carriers or anti-cancer vaccines. Thus, sEVs further provide novel avenues for cancer diagnosis and treatment. This review will focus on the role of sEVs in GI-oncology and delineate their functions in cancer progression, diagnosis, and therapeutic use.

The Role of Human Milk Oligosaccharides in Myelination, Socio-Emotional and Language Development: Observational Data from Breast-Fed Infants in the United States of America.

Infancy is a critical period for neurodevelopment, which includes myelination, synaptogenesis, synaptic pruning, and the development of motor, social-emotional, and cognitive functions. Human milk provides essential nutrients to the infant's developing brain, especially during the first postnatal months. Human milk oligosaccharides (HMOs) are a major component of human milk, and there is growing evidence of the association of individual HMOs with cognitive development in early life. However, to our knowledge, no study has explained these associations with a mechanism of action. Here, we investigated possible mediating associations between HMOs in human milk, brain myelination (measured via myelin water fraction), and measures of motor, language (collected via the Bayley Scales of Infant and Toddler Development (Bayley-III)), and socioemotional development (collected via the Ages and Stages Questionnaire: Social-Emotional Version (ASQ-SE)) in healthy term-born breast-fed infants. The results revealed an association between 6'Sialyllactose and social skills that was mediated by myelination. Furthermore, associations of fucosylated HMOs with language outcomes were observed that were not mediated by myelination. These observations indicate the roles of specific HMOs in neurodevelopment and associated functional outcomes, such as social-emotional function and language development.

Impact of a Nutrient Formulation on Longitudinal Myelination, Cognition, and Behavior from Birth to 2 Years: A Randomized Clinical Trial.

Observation studies suggest differences in myelination in relation to differences in early life nutrition. This two-center randomized controlled trial investigates the effect of a 12-month nutritional intervention on longitudinal changes in myelination, cognition, and behavior. Eighty-one full-term, neurotypical infants were randomized into an investigational (N = 42) or a control group (N = 39), receiving higher versus lower levels of a blend of nutrients. Non-randomized breastfed infants (N = 108) served as a reference group. Main outcomes were myelination (MRI), neurodevelopment (Bayley-III), social-emotional development (ASQ:SE-2), infant and toddler behavior (IBQ-R and TBAQ), and infant sleep (BISQ) during the first 2 years of life. The full analysis set comprised N = 67 infants from the randomized groups, with 81 myelin-sensitive MRI sequences. Significantly higher myelination was observed in the investigational compared to the control group at 6, 12, 18, and 24 months of life, as well as significantly higher gray matter volume at 24 months, a reduced number of night awakenings at 6 months, increased day sleep at 12 months, and reduced social fearfulness at 24 months. The results suggest that brain development may be modifiable with brain- and age-relevant nutritional approaches in healthy infants and young children, which may be foundational for later learning outcomes.

Human milk oligosaccharide composition and associations with growth: results from an observational study in the US.

Background: Breast milk is the recommended source of nutrients for newborns and infants. Human milk oligosaccharides (HMO) are the third most abundant solid component in human milk and their composition varies during lactation. Objectives: Our objective was to investigate longitudinal and cross-sectional changes in HMO composition and whether these changes were associated with infant growth up to 24 months of age. Associations with maternal characteristics were also investigated. Methods: 24 HMOs were quantified in samples taken at 2 weeks (n = 107), 6 weeks (n = 97) and 3 months (n = 76), using high performance liquid chromatography. Body length, weight, and head circumference were measured at 8 timepoints, until 24 months. Clusters of breast milk samples, reflecting different HMO profiles, were found through a data-driven approach. Longitudinal associations were investigated using functional principal component analysis (FPCA) and used to characterize patterns in the growth trajectories. Results: Four clusters of samples with similar HMO composition were derived. Two patterns of growth were identified for length, body weight and head circumference via the FPCA approach, explaining more than 90% of the variance. The first pattern measured general growth while the second corresponded to an initial reduced velocity followed by an increased velocity ("higher velocity"). Higher velocity for weight and height was significantly associated with negative Lewis status. Concentrations of 3'GL, 3FL, 6'GL, DSNLT, LNFP-II, LNFP-III, LNT, LSTb were negatively associated with higher velocity for length. Conclusion: We introduced novel statistical approaches to establish longitudinal associations between HMOs evolution and growth. Based on our approach we propose that HMOs may act synergistically on children growth. A possible causal relationship should be further tested in pre-clinical and clinical setting.

Dynamic Interplay between Social Brain Development and Nutrient Intake in Young Children.

Myelination of the brain structures underlying social behavior in humans is a dynamic process that parallels the emergence of social-emotional development and social skills in early life. Of the many genetic and environmental factors regulating the myelination processes, nutrition is considered as a critical and modifiable early-life factor for establishing healthy social brain networks. However, the impact of nutrition on the longitudinal development of social brain myelination remains to be fully understood. This study examined the interplay between childhood nutrient intake and social brain development across the first 5 years of life. Myelin-sensitive neuroimaging and food-intake data were analyzed in 293 children, 0.5 to 5 years of age, and explored for dynamic patterns of nutrient-social brain myelin associations. We found three data-driven age windows with specific nutrient correlation patterns, 63 individual nutrient-myelin correlations, and six nutrient combinations with a statistically significant predictive value for social brain myelination. These results provide novel insights into the impact of specific nutrient intakes on early brain development, in particular social brain regions, and suggest a critical age-sensitive opportunity to impact these brain regions for potential longer-term improvements in socio-emotional development and related executive-function and critical-thinking skills.

Associations between sleep trajectories up to 54 months and cognitive school readiness in 4 year old preschool children.

Purpose: This study explores the association between the duration and variation of infant sleep trajectories and subsequent cognitive school readiness at 48-50 months. Methods: Participants were 288 multi-ethnic children, within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Caregiver-reported total, night and day sleep durations were obtained at 3, 6, 9, 12, 18, 24 using the Brief Infant Sleep Questionnaire and 54 months using the Child Sleep Habits Questionnaire. Total, night and day sleep trajectories with varying durations (short, moderate, or long) and variability (consistent or variable; defined by standard errors) were identified. The cognitive school readiness test battery was administered when the children were between 48 and 50 months old. Both unadjusted adjusted analysis of variance models and adjusted analysis of covariance models (for confounders) were performed to assess associations between sleep trajectories and individual school readiness tests in the domains of language, numeracy, general cognition and memory. Results: In the unadjusted models, children with short variable total sleep trajectories had poorer performance on language tests compared to those with longer and more consistent trajectories. In both unadjusted and adjusted models, children with short variable night sleep trajectories had poorer numeracy knowledge compared to their counterparts with long consistent night sleep trajectories. There were no equivalent associations between sleep trajectories and school readiness performance for tests in the general cognition or memory domains. There were no significant findings for day sleep trajectories. Conclusion: Findings suggest that individual differences in longitudinal sleep duration patterns from as early as 3 months of age may be associated with language and numeracy aspects of school readiness at 48-50 months of age. This is important, as early school readiness, particularly the domains of language and mathematics, is a key predictor of subsequent academic achievement.

Endothelial Protein kinase D1 is a major regulator of post-traumatic hyperinflammation.

Trauma is a major cause of death worldwide. The post-traumatic immune response culminates in the release of pro-inflammatory mediators, translating in the infiltration of neutrophils (PMNs) at injury sites. The extent of this inflammation is determined by multiple factors, such as PMN adhesion to the endothelium, transendothelial migration, endothelial barrier integrity as well as PMN swarming, mass infiltration and activation. This process is initiated by secondary lipid mediators, such as leukotriene B4 (LTB4). We here provide evidence that Protein kinase D1 (PRKD1) in endothelial cells is implicated in all these processes. Endothelial PRKD1 is activated by pro-inflammatory stimuli and amplifies PMN-mediated inflammation by upregulation of cytokine and chemokines as well as adhesion molecules, such as ICAM-1, VCAM-1 and E-selectin. This induces enhanced PMN adhesion and trans-migration. PRKD1 activation also destabilizes endothelial VE-cadherin adhesion complexes and thus the endothelial barrier, fostering PMN infiltration. We even describe a yet unrecognized PRKD1-dependant mechanism to induce biosynthesis of the PMN-swarming mediator LTB4 directed via intercellular communication through small extracellular vesicles (sEVs) and enhanced CXCL8 secretion from activated endothelial cells. These endothelial sEVs transfer the LTB4 biosynthesis enzyme LTA4 hydrolase (LTA4H) to prime PMNs, while initiating biosynthesis also requires additional signals, like CXCL8. We further demonstrate the respective LTA4H-positive sEVs in the serum of polytrauma patients, peaking 12 h post injury. Therefore, PRKD1 is a key regulator in the coordinated communication of the endothelium with PMNs and a vital signaling node during post-traumatic inflammation.

Associations between Early Life Nutrient Intakes and Brain Maturation Show Developmental Dynamics from Infancy to Toddlerhood: A Neuroimaging Observation Study.

BACKGROUND: Myelin imaging has increasingly been applied to study the impact of nutrition on brain development in recent years. Although individual dynamics for nutrient intakes and myelin trajectories previously have been investigated across childhood, the longitudinal interaction between both remains unclear in typically developed children. OBJECTIVES: The objective of this work was to explore the developmental dynamics of nutrient-myelin interactions from infancy to early childhood using myelin imaging as a marker for brain maturation. METHODS: Brain neuroimaging (1 scan per child) and dietary nutrient intake data were analyzed for 88 nutrients from 293 children (127 female, 62% White) from a longitudinal cohort study in the United States. A sliding window approach was used to investigate correlations between nutrient intakes and brain myelination over a continuous set of age windows. Image processing techniques (Sobel-filter vertical edge detection) were applied to determine age windows with unique association profiles, providing novel insight into how these relationships change with child age. RESULTS: We identified 3 nutrient-myelin windows covering the age range of 1-5 y: window 1 from 6 to 20 mo with 60% positive nutrient correlations, window 2 from 20 to 30 mo with 20% positive correlations, and window 3 from 30 to 60 mo with 37% positive correlations. The windows are aligned with reported myelin and white matter dynamics that change in the first 5 y from fast and steep (window 1) to continued but slower growth (window 3), with window 2 possibly representing the inflection period. CONCLUSIONS: To our knowledge, this is the first study in typically developing children demonstrating the developmental dynamics between early life nutrient intakes and brain maturation in toddlerhood. The knowledge can be applied for identifying targeted and brain-stage-appropriate nutritional interventions for this critical stage of brain development.

Trajectories of reported sleep duration associate with early childhood cognitive development.

STUDY OBJECTIVES: Examine how different trajectories of reported sleep duration associate with early childhood cognition. METHODS: Caregiver-reported sleep duration data (n = 330) were collected using the Brief Infant Sleep Questionnaire at 3, 6, 9, 12, 18, and 24 months and Children's Sleep Habits Questionnaire at 54 months. Multiple group-based day-, night-, and/or total sleep trajectories were derived-each differing in duration and variability. Bayley Scales of Infant and Toddler Development-III (Bayley-III) and the Kaufman Brief Intelligence Test- 2 (KBIT-2) were used to assess cognition at 24 and 54 months, respectively. RESULTS: Compared to short variable night sleep trajectory, long consistent night sleep trajectory was associated with higher scores on Bayley-III (cognition and language), while moderate/long consistent night sleep trajectories were associated with higher KBIT-2 (verbal and composite) scores. Children with a long consistent total sleep trajectory had higher Bayley-III (cognition and expressive language) and KBIT-2 (verbal and composite) scores compared to children with a short variable total sleep trajectory. Moderate consistent total sleep trajectory was associated with higher Bayley-III language and KBIT-2 verbal scores relative to the short variable total trajectory. Children with a long variable day sleep had lower Bayley-III (cognition and fine motor) and KBIT-2 (verbal and composite) scores compared to children with a short consistent day sleep trajectory. CONCLUSIONS: Longer and more consistent night- and total sleep trajectories, and a short day sleep trajectory in early childhood were associated with better cognition at 2 and 4.5 years.

Dietary tryptophan-rich protein hydrolysate can acutely impact physiological and psychological measures of mood and stress in healthy adults.

BACKGROUND: Tryptophan is the precursor to the mood regulating neurotransmitter serotonin. Its brain bioavailability from food can be dependent on the dietary source. Egg protein hydrolysate (EPH), a dietary supplement rich in tryptophan, has previously shown to acutely impact cognition, mood and stress benefits at 2 g dose. No data exist on the acute effects of lower doses in a food matrix. METHODS: This exploratory study tested the acute effects of low-doses EPH (0.5, 1 g) in a food matrix on cognition, mood and stress. The study employed a double-blinded randomized controlled parallel design in 45 participants with three arms. The effects of the interventions were measured after a multi-task cognitive stressor on blood biomarkers, self-reported mood states, performances of attention, autonomic parameters and, emotional reactivity responses from electroencephalographic recording. RESULTS: As compared to the reference, the 1 g EPH dose increased tryptophan bioavailability from baseline, and, both doses improved heart rate variability parameters related to parasympathetic activation while showing differences in the late neural response to negative versus neutral emotions. Post-hoc analyses indicated a gender difference in the baseline tryptophan bioavailability and further examination suggested the change in mood rating depends on the interaction between gender and change from baseline of tryptophan bioavailability. CONCLUSIONS: Overall, this study suggests that low levels of tryptophan rich EPH in a food matrix positively impact mood or stress in acute settings and adds to the body of evidence linking tryptophan and dietary sources thereof with these benefits. Confirmatory randomized controlled trials are needed to confirm these findings.Trial registration number: CER-VD N°2019-00218.

Early Life to Adult Brain Lipidome Dynamic: A Temporospatial Study Investigating Dietary Polar Lipid Supplementation Efficacy.

The lipid composition of the brain is well regulated during development, and the specific temporospatial distribution of various lipid species is essential for the development of optimal neural functions. Dietary lipids are the main source of brain lipids and thus contribute to the brain lipidome. Human milk is the only source of a dietary lipids for exclusively breastfed infant. Notably, it contains milk fat globule membrane (MFGM) enriched in polar lipids (PL). While early life is a key for early brain development, the interplay between dietary intake of polar lipids and spatial dynamics of lipid distribution during brain development is poorly understood. Here, we carried out an exploratory study to assess the early postnatal temporal profiling of brain lipidome between postnatal day (PND) 7 and PND 50 using matrix-assisted laser desorption ionization as a mass spectrometry imaging (MALDI-MSI) in an in vivo preclinical model. We also assessed the effect of chronic supplementation with PL extracted from alpha-lactalbumin-enriched whey protein concentrate (WPC) containing 10% lipids, including major lipid classes found in the brain (37% phospholipids and 15% sphingomyelin). MALDI-MSI of the spatial and temporal accretion of lipid species during brain development showed that the brain lipidome is changing heterogeneously along time during brain development. In addition, increases in 400+ PL supplement-dependent lipids were observed. PL supplementation had significant spatial and temporal effect on specific fatty esters, glycerophosphocholines, glycerophosphoethanolamines, and phosphosphingolipids. Interestingly, the average levels of these lipids per brain area tended to be constant in various brain structures across the age groups, paralleling the general brain growth. In contrast, other lipids, such as cytidine diphosphate diacylglycerol, diacylglycerophosphates, phosphocholines, specific ether-phosphoethanolamines, phosphosphingolipids, glycerophosphoinositols, and glycerophosphoserines showed clear age-dependent changes uncoupled from the general brain growth. These results suggest that the dietary PL supplementation may preferentially provide the building blocks for the general brain growth during development. Our findings add to the understanding of brain-nutrient relations, their temporospatial dynamics, and potential impact on neurodevelopment.

A Nutrient Formulation Affects Developmental Myelination in Term Infants: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Observational studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning. The study aims to investigate the efficacy of a blend of docosahexaenoic acid (DHA), arachidonic acid (ARA), iron, vitamin B12, folic acid, and sphingomyelin (SM) from a uniquely processed whey protein concentrate enriched in alpha-lactalbumin and phospholipids compared with a control formulation on myelination, cognitive, and behavioral development in the first 6 months of life. METHODS: These are 6-month results from an ongoing two-center, randomized controlled trial with a 12-month intervention period (completed for all participants). In this study, full term, neurotypical infants of both sexes (N = 81) were randomized into investigational (N = 42) or control groups (N = 39). In addition, non-randomized breast-fed children (N = 108) serve as a natural reference group. Main outcomes are myelination (MRI), cognitive (Bayley Scales of Infant and Toddler Development, 3rd edition [Bayley-III]), social-emotional development (Ages and Stages Questionnaires: Social-Emotional, 2nd edition [ASQ:SE-2]), sleep (Brief Infant Sleep Questionnaire [BISQ]), and safety (growth and adverse events [AEs]). RESULTS: The full analyses set comprises N = 66 infants. Significant differences in myelin structure, volume, and rate of myelination were observed in favor of the investigational myelin blend at 3 and 6 months of life. Effects were demonstrated for whole brain myelin and for cerebellar, parietal, occipital, and temporal regions, known to be functionally involved in sensory, motor, and language skills. No statistically significant differences were found for early behavior and cognition scores. CONCLUSIONS: This is the first study demonstrating the efficacy of a myelin nutrient blend in well-nourished, term infants on developmental myelination, which may be foundational for later cognitive and learning outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT03111927.

Connecting inside out: Development of the social brain in infants and toddlers with a focus on myelination as a marker of brain maturation.

Early childhood is a sensitive period for learning and social skill development. The maturation of cerebral regions underlying social processing lays the foundation for later social-emotional competence. This study explored myelin changes in social brain regions and their association with changes in parent-rated social-emotional development in a cohort of 129 children (64 females, 0-36 months, 77 White). Results reveal a steep increase in myelination throughout the social brain in the first 3 years of life that is significantly associated with social-emotional development scores. These findings add knowledge to the emerging picture of social brain development by describing neural underpinnings of human social behavior. They can contribute to identifying age-/stage-appropriate early life factors in this developmental domain.

Effects of Post-natal Dietary Milk Fat Globule Membrane Polar Lipid Supplementation on Motor Skills, Anxiety, and Long-Term Memory in Adulthood.

Early life nutrition critically impacts post-natal brain maturation and cognitive development. Post-natal dietary deficits in specific nutrients, such as lipids, minerals or vitamins are associated with brain maturation and cognitive impairments. Specifically, polar lipids (PL), such as sphingolipids and phospholipids, are important cellular membrane building blocks and are critical for brain connectivity due to their role in neurite outgrowth, synaptic formation, and myelination. In this preclinical study, we assessed the effects of a chronic supplementation with a source of PL extracted from an alpha-lactalbumin enriched whey protein containing 10% lipids from early life (post-natal day (PND) 7) to adulthood (PND 72) on adult motor skills, anxiety, and long-term memory. The motor skills were assessed using open field and rotarod test. Anxiety was assessed using elevated plus maze (EPM). Long-term object and spatial memory were assessed using novel object recognition (NOR) and Morris water maze (MWM). Our results suggest that chronic PL supplementation improved measures of spatial long-term memory accuracy and cognitive flexibility in the MWM in adulthood, with no change in general mobility, anxiety and exploratory behavior. Our results indicate memory specific functional benefits of long-term dietary PL during post-natal brain development.

Soothing Effect of an Edible Teether: A Pilot Study in Children during Primary Dentition Age.

BACKGROUND: Irritability and discomfort are common symptoms during teething periods in infants and toddlers. Non-pharmacological remedies to relieve teething symptoms include teethers and food for chewing. However, the efficacy of such remedies for their soothing effect has been poorly investigated. MATERIALS AND METHODS: In this home-based pilot study, the soothing effect of a novel edible teether with a slowly dissolvable texture was investigated in 12 children aged 5 to 19 months old during primary dentition age. After parents observed their child getting irritable, the child received the edible teether for an exposure duration of 15 to 20 minutes. Parental ratings of children's mood states (crankiness, stress, happiness, and calmness) were collected using visual analog scales, and child cardiac measurements (heart rate and heart rate variability) were assessed using a wearable device. The soothing effect was quantified via mood ratings and physiological calming responses as a before-after comparison using Wilcoxon signed-rank tests. RESULTS: Parents perceived their child as significantly calmer and happier, less stressed, and marginally less cranky after edible teether exposure than before. The child cardiac variables showed no significant changes; however, exposure to the teether induced a marginal increase in HR within normal ranges, potentially indicating a stimulation effect. CONCLUSION: The pilot study provides the first insight on the soothing effect of a novel edible teether on parent-reported mood states in young children during primary dentition age. Further research is needed to understand the relative contribution of the different components of an edible teether to the observed effects, such as texture and exposure duration, and to demonstrate its efficacy against a control product. TRIAL REGISTRATION: Swiss registry of clinical trial: CER-VD 2019-02155. HOW TO CITE THIS ARTICLE: Lerond C, Hudry J, Zahar S, et al. Soothing Effect of an Edible Teether: A Pilot Study in Children during Primary Dentition Age. Int J Clin Pediatr Dent 2021;14(4):525-530.

Sialylated human milk oligosaccharides program cognitive development through a non-genomic transmission mode.

Breastmilk contains bioactive molecules essential for brain and cognitive development. While sialylated human milk oligosaccharides (HMOs) have been implicated in phenotypic programming, their selective role and underlying mechanisms remained elusive. Here, we investigated the long-term consequences of a selective lactational deprivation of a specific sialylated HMO in mice. We capitalized on a knock-out (KO) mouse model (B6.129-St6gal1tm2Jxm/J) lacking the gene responsible for the synthesis of sialyl(alpha2,6)lactose (6'SL), one of the two sources of sialic acid (Neu5Ac) to the lactating offspring. Neu5Ac is involved in the formation of brain structures sustaining cognition. To deprive lactating offspring of 6'SL, we cross-fostered newborn wild-type (WT) pups to KO dams, which provide 6'SL-deficient milk. To test whether lactational 6'SL deprivation affects cognitive capabilities in adulthood, we assessed attention, perseveration, and memory. To detail the associated endophenotypes, we investigated hippocampal electrophysiology, plasma metabolomics, and gut microbiota composition. To investigate the underlying molecular mechanisms, we assessed gene expression (at eye-opening and in adulthood) in two brain regions mediating executive functions and memory (hippocampus and prefrontal cortex, PFC). Compared to control mice, WT offspring deprived of 6'SL during lactation exhibited consistent alterations in all cognitive functions addressed, hippocampal electrophysiology, and in pathways regulating the serotonergic system (identified through gut microbiota and plasma metabolomics). These were associated with a site- (PFC) and time-specific (eye-opening) reduced expression of genes involved in central nervous system development. Our data suggest that 6'SL in maternal milk adjusts cognitive development through a short-term upregulation of genes modulating neuronal patterning in the PFC.

Variations in longitudinal sleep duration trajectories from infancy to early childhood.

OBJECTIVE: This study investigates variations in night, day, and total sleep trajectories across infancy and childhood in Asian children. PARTICIPANTS: Participants consisted of a subset of 901 children, within the Growing Up in Singapore Towards healthy Outcomes cohort, which recruited 1247 pregnant women between June 2009 and September 2010. DESIGN: We used a novel conditional probabilistic trajectory model: a probabilistic model for mixture distribution, allowing different trajectory curves and model variances among groups to cluster longitudinal observations. Longitudinal sleep duration data for the trajectory analyses were collected from caregiver-reported questionnaires at 3, 6, 9, 12, 18, 24, and 54 months. RESULTS: We found 3 patterns of night sleep trajectories (n = 356): long consistent (31%), moderate consistent (41%), and short variable (28%); and 4 patterns of day sleep trajectories (n = 347): long variable (21%), long consistent (20%), moderate consistent (34%), and short consistent (25%). We also identified 4 patterns of total sleep trajectories (n = 345): long variable (19%), long consistent (26%), moderate consistent (28%), and short variable (27%). Short, moderate, and long trajectories differed significantly in duration. Children with consistent trajectories also displayed sleep patterns that were significantly more representative of typical developmental sleep patterns than children with variable trajectories. CONCLUSIONS: This is the first study to describe multiple sleep trajectories in Singaporean children and identify between-individual variability within the trajectory groups. Compared to predominantly Caucasian samples, night/total sleep trajectories were generally shorter, while day sleep trajectories were longer. Future studies should investigate how these variations are linked to different developmental outcomes.

Nutrients for executive function development and related brain connectivity in school-aged children.

Executive functions refer to a set of higher-order cognitive processes involved in the control and organization of information to serve goal-directed behaviors. Skills in executive functioning are developed throughout childhood and adolescence and have been shown to be predictive of academic achievement. The coordination of these complex processes is critically dependent on brain maturation and connectivity, including key neurodevelopmental processes like myelination and synaptogenesis. Among other factors, research highlights the influential effect of nutrition and diet on these neurodevelopmental processes, which may impact executive function performance in healthy and deficient populations. This review considers the research to date on the role of key nutrients that have been identified for executive function development and their underlying neurophysiological processes in school-aged children.

Body mass index and self-reported body image in German adolescents.

BACKGROUND: Despite knowledge about eating disorder symptoms in children and adolescents in the general population, relatively little is known about self-reported and sex-specific eating-disorder-related psychopathology, as well as its specific correlates. METHODS: 880 German school-attending adolescents (15.4 ± 2.2 years) and 30 female patients with AN (16.2 ± 1.6 years) were studied. All participants completed the Eating Disorder Inventory-2 and a Body Image Questionnaire. RESULTS: There were more overweight males than females (15.2% vs 10.1%, p < 0.001), but more females with underweight than males (6.2% vs. 2.5%, p < .001). Negative body evaluations (p < .001) and dissatisfaction (p < .001) were significantly more frequent in females. Compared to underweight female patients with AN, underweight school-attending females had less negative body evaluations (p < .001) and lower scores on 5 of the 11 EDI-2 subscales (p < .001; p < .05). CONCLUSIONS: Males were more overweight than females, females more underweight. Body image was more important to female than to male youth, yet without reaching pathological values when compared to female patients with AN. Complex emotional and cognitive challenges seem to be a representative factor for eating pathology rather than simply being underweight. These aspects may be relevant for the shift from a thinness-related focus in girls in the general population to the development of an eating disorder.

Postpartal Affective and Endocrine Differences Between Parents of Preterm and Full-Term Infants.

BACKGROUND: During the postpartum period, new parents frequently experience emotional stress and exhibit symptoms of depression and anxiety, accompanied by substantial endocrine changes. However, evidence predominantly exists from parents of full-term infants, while data on parents of preterm infants are scarce. In this exploratory, cross-sectional study, we compared psychological well-being and endocrine parameters in parents of very preterm and term born infants. METHODS: Mothers (N = 28) and fathers (N = 30) of full-term infants as well as mothers (N = 18) and fathers (N = 21) of very or extreme preterm infants (< 32nd gestational week) were recruited in the days following birth. Anxiety, depression, and perceived stress were assessed with the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), and the Perceived Stress Questionnaire (PSQ), respectively. Physiological measures included serum levels of estradiol, progesterone, prolactin, and thyroid-stimulating hormone (mothers only), as well as the salivary cortisol awakening response (mothers and fathers). RESULTS: New mothers and fathers of very preterm infants exhibited higher scores of depression, anxiety and stress than parents of term infants. Besides, mothers of very preterm infants showed lower levels of estradiol, progesterone, and prolactin, as well as a heightened post-awakening cortisol response compared to mothers of term infants. Furthermore, in mothers of preterm infants we found significant negative associations between serum prolactin levels and BDI and STAI scores, respectively. CONCLUSIONS: Parents of very preterm infants suffered from a higher burden of psychological distress than parents of full-term infants. The affective symptoms in preterm mothers were accompanied by altered endocrine profiles that, at least to some extent, may contribute to the psychological changes. The profound psychological and physiological disturbances in mothers of preterm infants may have an impact on long-term mental health and early pharmacological and psychological interventions may help to ameliorate postpartum affective symptoms.