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DNA methylation is closely related to folate levels and acts as a mechanism linking developmental disorders to chronic diseases. Folic acid supplementation can impact DNA methylation levels of imprinted genes crucial for neonatal development. Imprinted genes are vital for regulating embryonic and postnatal fetal growth. This review summarizes imprinted genes, DNA methylation, folic acid's influence on growth and development and their correlation. It aims to provide a comprehensive overview of research advancements on imprinted genes, DNA methylation and folic acid regulation concerning growth and development.

Objectives: Investigations of early childhood growth among small-scale populations are essential for understanding human life history variation and enhancing the ability to serve such communities through global public health initiatives. This study characterizes early childhood growth trajectories and identifies differences in growth patterns relative to international references among Daasanach semi-nomadic pastoralist children living in a hot, arid region of northern Kenya., Methods: A large sample of height and weight measures were collected from children (N = 1756; total observations = 4508; age = 0-5 years) between 2018 and 2020. Daasanach growth was compared to international reference standards and Daasanach-specific centile growth curves and pseudo-velocity models were generated using generalized additive models for location scale and size., Results: Compared to World Health Organization (WHO) reference, relatively few Daasanach children were stunted (14.3%), while a large proportion were underweight (38.5%) and wasted (53.6%). Additionally, Daasanach children had a distinctive pattern of growth, marked by an increase in linear growth velocity after 24 months of age and relatively high linear growth velocity throughout the rest of early childhood., Conclusions: These results identify a unique pattern of early childhood growth faltering among children in a small-scale population and may reflect a thermoregulatory adaptation to their hot, arid environment. As linear growth and weight gain remain important indicators of health, the results of this study provide insight into growth velocity variations. This study has important implications for global public health efforts to identify and address sources of early growth faltering and undernutrition in small-scale populations., (© 2022 Wiley Periodicals LLC.)

The NMDA receptor is a Ca 2+ -permeant glutamate receptor which plays key roles in health and disease. Canonical NMDARs contain two GluN2 subunits, of which 2A and 2B are predominant in the forebrain. Moreover, the relative contribution of 2A vs. 2B is controlled both developmentally and in an activity-dependent manner. The GluN2 subtype influences the biophysical properties of the receptor through difference in their N-terminal extracellular domain and transmembrane regions, but they also have large cytoplasmic Carboxyl (C)-terminal domains (CTDs) which have diverged substantially during evolution. While the CTD identity does not influence NMDAR subunit specific channel properties, it determines the nature of CTD-associated signalling molecules and has been implicated in mediating the control of subunit composition (2A vs. 2B) at the synapse. Historically, much of the research into the differential function of GluN2 CTDs has been conducted in vitro by over-expressing mutant subunits, but more recently, the generation of knock-in (KI) mouse models have allowed CTD function to be probed in vivo and in ex vivo systems without heterologous expression of GluN2 mutants. In some instances, findings involving KI mice have been in disagreement with models that were proposed based on earlier approaches. This review will examine the current research with the aim of addressing these controversies and how methodology may contribute to differences between studies. We will also discuss the outstanding questions regarding the role of GluN2 CTD sequences in regulating NMDAR subunit composition, as well as their relevance to neurodegenerative disease and neurodevelopmental disorders.

Alterations in the nutritional environment in early life can significantly increase the risk for obesity and a range of development of metabolic disorders in offspring in later life, effects that can be passed onto future generations. This process, termed development programming, provides the framework of the developmental origins of health and disease (DOHaD) paradigm. Early life nutritional compromise including undernutrition, overnutrition or specific macro/micronutrient deficiencies, results in a range of adverse health outcomes in offspring that can be further exacerbated by a poor postnatal nutritional environment. Although the mechanisms underlying programming remain poorly defined, a common feature across the phenotypes displayed in preclinical models is that of altered wiring of neuroendocrine circuits that regulate satiety and energy balance. As such, altered maternal nutritional exposures during critical early periods of developmental plasticity can result in aberrant hardwiring of these circuits with lasting adverse consequences for the offspring. There is also increasing evidence around the role of an altered epigenome and the gut-brain axis in mediating some of the central programming effects observed. Further, although such programming was once considered to result in a permanent change in developmental trajectory, there is evidence, at least from preclinical models, that programming can be reversed via targeted nutritional manipulations during early development. Further work is required at a mechanistic level to allow for identification for early markers of later disease risk, delineation of sex-specific effects and pathways to implementation of strategies aimed at breaking the transgenerational transmission of disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study evaluates the effectiveness of an early childhood tele-education program in preparing community pediatric clinicians to manage developmental and mental health disorders in young children. Community pediatric clinicians from rural, underserved, or school-based health center practices in the mid-Atlantic region participated in a weekly tele-education videoconference. There was a significant knowledge gain evidenced by the percentage of questions answered correctly from pre- to post- didactic exposure ( P < .001). Participants reported an increase in knowledge from pre- ( P < .001) and in confidence from pre- to post- participation ( P < .001). Practice management changes demonstrated an encouraging trend toward managing patients in the Medical Home, as compared with immediately deferring to specialists following participation. This early childhood tele-education videoconferencing program is a promising response to the urgent need to confidently increase the role of pediatricians in the provision of care for childhood developmental and mental health disorders.

Introduction: Introduction: physical growth patterns and nutritional status of children and adolescents living at a moderate altitude are not applicable for clinical assessment of growth for diverse populations around the world. Objective: a) to compare weight, height and body mass index (BMI) variables with CDC-2012 references; b) to verify if BMI and/or ponderal index (PI) are applicable to children living at a moderate altitude; and c) to propose percentiles to assess physical growth by age and sex. Methods: a total of 5,377 students, ranging in age from 6.0 to 17.9 years, were evaluated. The students were from two geographic regions of moderate altitude in Peru (2,320 meters) and Colombia (2,640 meters). Weight and height were measured. BMI and PI were calculated. Weight, height and BMI were compared with CDC-2012 references. Results: males showed lower weight and height from age 11 to 17.9 years compared to CDC-2012. Females weighed less than the reference from 9.0 to 17.9 years. Female height was lower from 6.0 to 14.9 years; however, from 15.0 to 17.9 years, values were similar to the reference. As for BMI, there were differences in both sexes (in males, from 15.0 to 17.9 years, and in females, from 12.0 to 17.9 years). Age, weight and height explained BMI: between R2 = 17 and 83 % in males, and in females between R2 = 24 and 85 %. These same variables influenced PI in a lower percentage in both sexes: for males (R2 = 0.01 to 49 %) and for females (R2 = 0.01 to 18 %). Conclusions: children and adolescents living at a moderate altitude in Peru and Colombia diverge from the CDC-2012 physical growth patterns. In addition, PI is a new alternative for estimating weight in relation to BMI. The proposed curves for weight, height, and PI by age and sex could have greater implications in the control of child health programs and in clinical and epidemiological practices.

Background: Cortisol-producing adrenocortical adenoma (CPA) during pregnancy rarely occurs in clinic. Growing evidence suggests that DNA methylation plays a key role in adrenocortical adenomas. The present study aims to examine the genome-wide DNA methylation profiles and identify the differences in DNA methylation signatures of non-pregnant and pregnant patients with CPA., Results: Four pregnant and twelve non-pregnant patients with CPA were enrolled. The pregnant patients with CPA had higher serum cortisol, Estradiol, Progesterone, and human chorionic gonadotropin concentration, while having lower serum FSH (follicle-stimulating hormone) and luteinizing hormone concentrations (P < 0.01). Compared with the non-pregnant patients, the duration is shorter, and the growth rate of the tumor is faster in pregnant patients with CPA (P < 0.05). Morphology and cell proliferation assay showed that the percentage of Ki-67 positive cells in CPA were higher in pregnant group than non-pregnant group (8.0% vs 5.5%, P < 0.05). The DNA methylation analysis showed that Genome-wide DNA methylation signature difference between pregnant and non-pregnant with CPA, that the pregnant group had more hypermethylated DMPs (67.94% vs 22.16%) and less hypomethylated DMPs (32.93% vs 77.84%). The proportion of hypermethylated DMPs was relatively high on chromosomes 1 (9.68% vs 8.67%) and X (4.99% vs 3.35%) but lower on chromosome 2(7.98% vs 12.92%). In pregnant patients with CPA, 576 hypomethylated DMPs and 1109 hypermethylated DMPs were identified in the DNA promoter region. Bioinformatics analysis indicated that the Wnt/β-Catenin pathway, Ras/MAPK Pathway and PI3K-AKT Pathway were associated with the development of CPA during pregnancy., Conclusions: Genome-wide DNA methylation profiling of CPA in non-pregnant and pregnant patients was identified in the present study. Alterations of DNA methylation were associated with the pathogenesis and exacerbation of CPA during pregnancy., (© 2021. The Author(s).)

Optimizing enteral nutrition for premature infants may help mitigate extrauterine growth restriction and adverse chronic health outcomes. Previously, we showed in neonatal pigs born at term that lean growth is enhanced by intermittent bolus compared with continuous feeding. The objective was to determine if prematurity impacts how body composition, muscle protein synthesis, and myonuclear accretion respond to feeding modality. Following preterm delivery, pigs were fed equivalent amounts of formula delivered either as intermittent boluses (INT; n = 30) or continuously (CONT; n = 14) for 21 days. Body composition was measured by dual-energy X-ray absorptiometry (DXA) and muscle growth was assessed by morphometry, myonuclear accretion, and satellite cell abundance. Tissue anabolic signaling and fractional protein synthesis rates were determined in INT pigs in postabsorptive (INT-PA) and postprandial (INT-PP) states and in CONT pigs. Body weight gain and composition did not differ between INT and CONT pigs. Longissimus dorsi (LD) protein synthesis was 34% greater in INT-PP than INT-PA pigs ( P < 0.05) but was not different between INT-PP and CONT pigs. Phosphorylation of 4EBP1 and S6K1 and eIF4E·eIF4G abundance in LD paralleled changes in LD protein synthesis. Satellite cell abundance, myonuclear accretion, and fiber cross-sectional area in LD did not differ between groups. These results suggest that, unlike pigs born at term, intermittent bolus feeding does not enhance lean growth more than continuous feeding in pigs born preterm. Premature birth attenuates the capacity of skeletal muscle to respond to cyclical surges in insulin and amino acids with intermittent feeding in early postnatal life. NEW & NOTEWORTHY Extrauterine growth restriction often occurs in premature infants but may be mitigated by optimizing enteral feeding strategies. We show that intermittent bolus feeding does not increase skeletal muscle protein synthesis, myonuclear accretion, or lean growth more than continuous feeding in preterm pigs. This attenuated anabolic response of muscle to intermittent bolus feeding, compared with previous observations in pigs born at term, may contribute to deficits in lean mass that many premature infants exhibit into adulthood.

Respiratory distress syndrome results from inadequate functional pulmonary surfactant and is a significant cause of mortality in preterm infants. Surfactant is essential for regulating alveolar interfacial surface tension, and its synthesis by Type II alveolar epithelial cells is stimulated by leptin produced by pulmonary lipofibroblasts upon activation by peroxisome proliferator-activated receptor γ (PPARγ). As it is unknown whether PPARγ stimulation or direct leptin administration can stimulate surfactant synthesis before birth, we examined the effect of continuous fetal administration of either the PPARγ agonist, rosiglitazone (RGZ; Study 1) or leptin (Study 2) on surfactant protein maturation in the late gestation fetal sheep lung. We measured mRNA expression of genes involved in surfactant maturation and showed that RGZ treatment reduced mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies), but did not alter mRNA expression of PPARγ, surfactant proteins (SFTP-A, -B, -C, and -D), PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation), or the PPARγ target genes SPHK-1 and PAI-1. Leptin infusion significantly increased the expression of PPARγ and IGF2 and decreased the expression of SFTP-B. However, mRNA expression of the majority of genes involved in surfactant synthesis was not affected. These results suggest a potential decreased capacity for surfactant phospholipid and protein production in the fetal lung after RGZ and leptin administration, respectively. Therefore, targeting PPARγ may not be a feasible mechanistic approach to promote lung maturation.

Rapid infant growth increases the risk for adult obesity. The gut microbiome is associated with early weight status; however, no study has examined how interactions between microbial and host ribonucleic acid (RNA) expression influence infant growth. We hypothesized that dynamics in infant stool micro-ribonucleic acids (miRNAs) would be associated with both microbial activity and infant growth via putative metabolic targets. Stool was collected twice from 30 full-term infants, at 1 month and again between 6 and 12 months. Stool RNA were measured with high-throughput sequencing and aligned to human and microbial databases. Infant growth was measured by weight-for-length z-score at birth and 12 months. Increased RNA transcriptional activity of Clostridia (R = 0.55; Adj p = 3.7E-2) and Burkholderia (R = -0.820, Adj p = 2.62E-3) were associated with infant growth. Of the 25 human RNAs associated with growth, 16 were miRNAs. The miRNAs demonstrated significant target enrichment (Adj p < 0.05) for four metabolic pathways. There were four associations between growth-related miRNAs and growth-related phyla. We have shown that longitudinal trends in gut microbiota activity and human miRNA levels are associated with infant growth and the metabolic targets of miRNAs suggest these molecules may regulate the biosynthetic landscape of the gut and influence microbial activity.

Background: The gut microbiome is an important determinant of health and disease in preterm infants., Objectives: The objective of this article was to share our current protocol for other neonatal intensive care units to potentially expand their existing protocols, aiming to characterize the relationship between the intestinal microbiome and health outcomes in preterm infants., Methods: This prospective, longitudinal study planned to recruit 160 preterm infants born <32 weeks gestational age or weighing <1,500 g and admitted to one of two Level III/IV neonatal intensive care units. During the neonatal intensive care unit period, the primary measures included events of early life pain/stress, gut microbiome, host genetic variations, and neurobehavioral assessment. During follow-up visits, gut microbiome; pain sensitivity; and medical, growth, and developmental outcomes at 4, 8-12, and 18-24 months corrected age were measured., Discussion: As of February 14, 2020, 214 preterm infants have been recruited. We hypothesize that infants who experience greater levels of pain/stress will have altered gut microbiome, including potential adverse outcomes such as necrotizing enterocolitis and host genetic variations, feeding intolerance, and/or neurodevelopmental impairments. These will differ from the intestinal microbiome of preterm infants who do not develop these adverse outcomes. To test this hypothesis, we will determine how alterations in the intestinal microbiome affect the risk of developing necrotizing enterocolitis, feeding intolerance, and neurodevelopmental impairments in preterm infants. In addition, we will examine the interaction between the intestinal microbiome and host genetics in the regulation of intestinal health and neurodevelopmental outcomes., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Introduction: during childhood and adolescence there is great individual variability in growth and biological maturation, resulting in differences in size, shape and body composition in children and adolescents of similar age. Objective: to propose percentiles to assess physical growth and body adiposity as a function of maturity status (SM) in Chilean children and adolescents. Methods: a descriptive (cross-sectional) study was designed in 7,292 children and adolescents (4214 boys and 3084 girls) from the Maule region (Chile). The age range was 6.0 to 17.9 years. Weight, height and waist circumference (WC) were evaluated. Body mass index (BMI), waist-height index (WHtR) and SM were calculated through a non-invasive anthropometric technique based on chronological age and standing height. The LMS method was used to calculate percentiles. Results: the SM calculated in boys was observed at 13.7 ± 0.6 APHV (years of peak growth speed) and in girls at 12.1 ± 0.6 APHV. Percentiles were created for weight, height, WC, BMI, and WHtR. All anthropometric variables increase as MS increases in PHV years. Conclusion: the proposed percentiles are an alternative to evaluate physical growth and body adiposity as a function of SM in Chilean children and adolescents. The results suggest the use of this non-invasive technique to be applied in clinical and epidemiological contexts.

Introduction: Metabolomics may identify biological pathways predisposing children to the risk of overweight and obesity. In this study, we have investigated the cord blood metabolic signatures of rapid growth in infancy and overweight in early childhood in four European birth cohorts., Methods: Untargeted liquid chromatography-mass spectrometry metabolomic profiles were measured in cord blood from 399 newborns from four European cohorts (ENVIRONAGE, Rhea, INMA and Piccolipiu). Rapid growth in the first year of life and overweight in childhood was defined with reference to WHO growth charts. Metabolome-wide association scans for rapid growth and overweight on over 4500 metabolic features were performed using multiple adjusted logistic mixed-effect models and controlling the false discovery rate (FDR) at 5%. In addition, we performed a look-up analysis of 43 pre-annotated metabolites, previously associated with birthweight or rapid growth., Results: In the Metabolome-Wide Association Study analysis, we identified three and eight metabolites associated with rapid growth and overweight, respectively, after FDR correction. Higher levels of cholestenone, a cholesterol derivative produced by microbial catabolism, were predictive of rapid growth (p = 1.6 × 10 -3 ). Lower levels of the branched-chain amino acid (BCAA) valine (p = 8.6 × 10 -6 ) were predictive of overweight in childhood. The area under the receiver operator curve for multivariate prediction models including these metabolites and traditional risk factors was 0.77 for rapid growth and 0.82 for overweight, compared with 0.69 and 0.69, respectively, for models using traditional risk factors alone. Among the 43 pre-annotated metabolites, seven and five metabolites were nominally associated (P < 0.05) with rapid growth and overweight, respectively. The BCAA leucine, remained associated (1.6 × 10 -3 ) with overweight after FDR correction., Conclusion: The metabolites identified here may assist in the identification of children at risk of developing obesity and improve understanding of mechanisms involved in postnatal growth. Cholestenone and BCAAs are suggestive of a role of the gut microbiome and nutrient signalling respectively in child growth trajectories., (© 2021. The Author(s).)

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD) is the closest animal model available to the human situation. This paradigm induces long lasting behavioral effects, causes changes in the HPA axis and affects the immune system. However, the mechanisms underlying changes in the immune response after ELA are still not fully understood. In this study we investigated how ELA changes the immune system, through an unbiased analysis, viSNE, and addressed specially the NK immune cell population and its functionality. We have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells' profile and response to target cell lines are significantly changed after ELA. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. These results suggest that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fernandes, Patil, Meriaux, Theresine, Muller, Leenen, Elwenspoek, Zimmer and Turner.)

During valvulogenesis, cytoskeletal, secretory and transcriptional events drive endocardial cushion growth and remodeling into thin fibrous leaflets. Genetic disorders play an important role in understanding valve malformations but only account for a minority of clinical cases. Mechanical forces are ever present, but how they coordinate molecular and cellular decisions remains unclear. In this study, we used osmotic pressure to interrogate how compressive and tensile stresses influence valve growth and shape maturation. We found that compressive stress drives a growth phenotype, whereas tensile stress increases compaction. We identified a mechanically activated switch between valve growth and maturation, by which compression induces cushion growth via BMP-pSMAD1/5, while tension induces maturation via pSer-19-mediated MLC2 contractility. The compressive stress acts through BMP signaling to increase cell proliferation and decrease cell contractility, and MEK-ERK is essential for both compressive stress and BMP mediation of compaction. We further showed that the effects of osmotic stress are conserved through the condensation and elongation stages of development. Together, our results demonstrate that compressive/tensile stress regulation of BMP-pSMAD1/5 and MLC2 contractility orchestrates valve growth and remodeling., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

This article is the eighth in a series on the biological basis of child health. It describes the embryological development of the gastrointestinal (GI) system and some of the structural anomalies that may arise during that time and later affect GI functioning. The article also discusses the functions of the GI tract - including ingestion, digestion, absorption and defecation - and explains how these relate to GI conditions seen in infants and children. GI conditions are common in childhood and some of these will be medical emergencies, so it is important that children's nurses have knowledge of the GI system and of the presentation and management of GI conditions in children., Competing Interests: None declared, (© 2020 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

A growing body of evidence indicates that neutrophils are the first major leukocyte population accumulating inside the pancreas even before the onset of a lymphocytic-driven impairment of functional beta cells in type 1 diabetes mellitus (T1D). In humans, pancreata from T1D deceased donors exhibit significant neutrophil accumulation. We present a time course of previously unknown inflammatory changes that accompany neutrophil and neutrophil elastase accumulation in the pancreas of the non-obese diabetic (NOD) mouse strain as early as 2 weeks of age. We confirm earlier findings in NOD mice that neutrophils accumulate as early as 2 weeks of age. We also observe a concurrent increase in the expression of neutrophil elastase in this time period. We also detect components of neutrophil extracellular traps (NET) mainly in the exocrine tissue of the pancreas during this time as well as markers of vascular pathology as early as 2 weeks of age. Age- and sex-matched C57BL/6 mice do not exhibit these features inside the pancreas. When we treated NOD mice with inhibitors of myeloperoxidase and neutrophil elastase, two key effectors of activated neutrophil activity, alone or in combination, we were unable to prevent the progression to hyperglycemia in any manner different from untreated control mice. Our data confirm and add to the body of evidence demonstrating neutrophil accumulation inside the pancreas of mice genetically susceptible to T1D and also offer novel insights into additional pathologic mechanisms involving the pancreatic vasculature that have, until now, not been discovered inside the pancreata of these mice. However, inhibition of key neutrophil enzymes expressed in activated neutrophils could not prevent diabetes. These findings add to the body of data supporting a role for neutrophils in the establishment of early pathology inside the pancreas, independently of, and earlier from the time at onset of lymphocytic infiltration. However, they also suggest that inhibition of neutrophils alone, acting via myeloperoxidase and neutrophil elastase only, in the absence of other other effector cells, is insufficient to alter the natural course of autoimmune diabetes, at least in the NOD model of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Garciafigueroa, Phillips, Engman, Trucco and Giannoukakis.)

Slow-growing broilers offer differentiation in the chicken meat market for consumers who have distinct preferences based on perceived higher welfare indices and willingness to pay a higher price for the product. Although breeding for slow-growing broilers is relatively advanced in Europe and the United States, it is limited in Australia. Crossbreeding is one of the approaches taken to developing slow-growing broiler strains. Thus, the aim of this study was to compare performance, immune response, leg health, carcass characteristics, and meat quality of a novel crossbred slow-growing broiler breed (SGB) with the conventional, fast-growing Cobb 500 broiler (CB) to assess their suitability as an alternative for chicken meat production in Australia. A total of 236 one-day-old broiler chicks (116 SGB and 120 fast-growing CB) were reared on standard commercial diet in an intensive production system. Birds and feed were weighed on a weekly basis and feed intake and feed conversion ratio calculated. At 21 d of age, a 2% suspension of sheep red blood cells was injected subcutaneously into 8 broilers of each breed to compare their antibody response. Birds from both breeds were grown to a final live weight of 2.0-2.2 kg, before a latency-to-lie (LTL) test, carcass analysis and apparent metabolizable energy (AME) assay were performed. The SGB reached the target weight at 55 d of age compared with 32 d in CB. However, SGB stood for longer during LTL, had higher thigh, drumstick, and wing yields (as a percentage of carcass weight) as well as darker and redder meat in comparison with the CB. The CB had better feed conversion efficiency, higher antibody (IgM) production, higher AME, heavier breast yield, and lower meat drip loss than the SGB. Although fast-growing CB outperformed the SGB for traditional performance parameters, the crossbred in this study was comparable with other slow-growing broiler breeds and strains across different countries and is thus a suitable candidate for a slow-growing alternative in Australia., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

This article is the sixth in a series on the biological basis of child health. It provides an overview of the development of the skeletal system before and after birth, and outlines the potential congenital anomalies that may occur. The article explains the structure and function of the bones before describing the role of the joints, tendons and ligaments. It also outlines the presentation and management of some of the common orthopaedic conditions seen in infants and children, including fractures, osteogenesis imperfecta, scoliosis, juvenile idiopathic arthritis, developmental dysplasia of the hip and achondroplasia., Competing Interests: None declared, (©2021 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Breast milk has been considered the best source of nutrition for newborns. Several epidemiological and basic experimental studies have been conducted to understand the nutritional advantages of breast milk. Previous findings have emphasized the importance of good maternal nutrition. Maternal milk provides macromolecules, minerals, immune cells, antibodies, hormones, and regular flora to strengthen their offspring preventing various diseases. Maternal milk helps to facilitate physiological, and molecular maturation of several systems, which are important for the final maturation of organs and newborn body development. Currently, breastfeeding is being abandoned for various reasons, such as lower milk production, lack of time, abandonment of the family, social or emotional problems and adverse environmental conditions. These permanent alterations during a critical developmental window have negative consequences in regard to the development of the offspring and organ maturation leading to metabolic, reproductive, hormonal and physiological problems from early life to adulthood. This review describes the advantages of breast milk and the importance for the mother to maintain an adequate diet during pregnancy and lactation, in addition to maintaining a healthy lifestyle and harmonious family relationships. Such an environment will contribute to the complete maturation and development of the offspring., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Skeletal muscle is sensitive to environmental cues that are first present in utero. Maternal overnutrition is a model of impaired muscle development leading to structural and metabolic dysfunction in adult life. In this study, we investigated the effect of an obesogenic maternal environment on growth and postnatal myogenesis in the offspring. Male C57BL/6J mice born to chow- or high-fat-diet-fed mothers were allocated to four different groups at the end of weaning. For the following 10 wk, half of the pups were maintained on the same diet as their mother and half of the pups were switched to the other diet (chow or high-fat). At 12 wk of age, muscle injury was induced using an intramuscular injection of barium chloride. Seven days later, mice were humanely killed and muscle tissue was harvested. A high-fat maternal diet impaired offspring growth patterns and downregulated satellite cell activation and markers of postnatal myogenesis 7 days after injury without altering the number of newly synthetized fibers over the whole 7-day period. Importantly, a healthy postnatal diet could not reverse any of these effects. In addition, we demonstrated that postnatal myogenesis was associated with a diet-independent upregulation of three miRNAs, mmu-miR-31-5p, mmu-miR-136-5p, and mmu-miR-296-5p. Furthermore, in vitro analysis confirmed the role of these miRNAs in myocyte proliferation. Our findings are the first to demonstrate that maternal overnutrition impairs markers of postnatal myogenesis in the offspring and are particularly relevant to today's society where the incidence of overweight/obesity in women of childbearing age is increasing.

Feather pecking and cannibalism are 2 major problems in laying hens' husbandry. Although additional environmental enrichment material (EM) supply is thought to lessen these problems, consistent evidences are lacking. This study examined the effects of EM supply (pecking stones and alfalfa bales) on biological performance, carcass composition, and animal losses in a littered housing system. 2,000 brown-egg and 2,000 white-egg layer hen pullets of the genetic strains Lohmann Brown classic and Lohmann Selected Leghorn classic, respectively, were reared separately in a 16-compartment aviary system until week 18. 1,320 remaining laying hens were then transferred to a 44-compartment laying stable (weeks 19-48). Both strains were tested under 4 treatment variants (n = 150-180 per strain and per variant): V1-no EM over the entire study period; V2-the rearing period with and the laying period without EM; V3-the rearing period without and the laying period with EM; V4-EM over the entire study period. Data on development, performance, egg quality, feed intake, EM consumption, animal losses, carcass composition, and economic traits were collected. Enrichment material supply during rearing (V2 and V4, both strains) was found to globally increase not only hens' relative gizzard mass (P = 0.036) but also the cracked eggs' percentage (compared with V3; P = 0.008) and to decrease the body mass in weeks 6 (P = 0.023) and 8 (P = 0.023) and the uniformity in week 16 (P = 0.011). Enrichment material provision during the laying period (V3 and V4, both strains) increased egg weights (P = 0.028) and the mean body mass (P = 0.036); however, continuous provision of EM (V4, both strains) increased the floor eggs' percentage (P = 0.019). The EM supply did not affect mortality, loss of production days, losses due to skin and toe cannibalism, or the income over feed costs. However, the income over feed and enrichment costs of V1 hens was higher by 0.55 €/hen than that of V4 hens (P = 0.022). Therefore, EM supply cannot be recommended as a measure to increase laying performance and reduce animal losses, but its positive effects on animal welfare should be considered., (Copyright © 2020. Published by Elsevier Inc.)

The aim of this study was to compare the dynamic changes of egg selenium (Se) deposition and deposition efficiency and to evaluate the efficacy of selenium-enriched yeast (SY) in laying hens over the 84 d feeding period after SY supplementation. A total of one thousand one hundred fifty-two 30-wk-old, Hy-Line Brown hens were randomly assigned to 1 of 6 groups (192 laying hens per group) with 6 replicates of 32 birds each, fed a basal diet (without Se supplementation), basal diet with 0.3 mg/kg of Se from sodium selenite (SS) or basal diets with 0.1, 0.2, 0.3, or 0.4 mg/kg of Se from SY, respectively. The results showed that the Se concentrations in the eggs and breasts from hens fed a SY-supplemented diet were significantly higher than those from hens fed a SS-supplemented diet or a basal diet (P < 0.001). There was a positive linear and quadratic correlation between Se concentrations in the eggs from hens fed a SY-supplemented diet and dietary Se supplementation on days 28, 56, and 84 (r 2  = 0.931, 0.932, 0.976, P < 0.001; r 2  = 0.946, 0.935, 0.976, P < 0.001), respectively. The Se deposition efficiency in whole eggs from hens fed a basal or SY-supplemented diet weresignificantly higher than those in eggs from hens fed a SS-supplemented diet on days 28, 56, and 84 (P < 0.001), respectively. In addition, there was a positive linear and quadratic correlation between Se concentrations in the eggs from hens fed SY-supplemented diet (r 2  = 0.655, 0.779, 0.874, 0.781, P < 0.001; r 2  = 0.666, 0.863, 0.944, 0.781, P < 0.001) or SS-supplemented diet (r 2  = 0.363, P = 0.002; r 2  = 0.440, P = 0.002) and number of feeding days. In conclusion, the organic Se from SY has higher bioavailability and deposition efficiency of Se in whole eggs as compared with inorganic Se from SS. The Se concentrations and Se deposition efficiency in the eggs increased from hens fed a SS- or SY-supplemented diet but decreased from hens fed a basal diet with the extension of the experimental duration. The results indicate that the dietary Se supplementation from SY should be limited to a maximum of 0.1 mg Se/kg complete feed when the eggs and meat produced from hens fed a SY-supplemented diet are used as food for humans directly, whereas up to 0.4 mg/kg organic Se from SY can be used to supplement the diets for laying hens when the products are used as raw materials for producing Se-enriched food., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: A life-course perspective emphasizes healthy behaviors before, during, and after pregnancy to support a multi-generational risk reduction in obesity for mothers and infants. Optimal timing, content, and dose of such interventions is not well defined., Methods: We conducted a nested cohort within a randomized trial to evaluate whether a healthy lifestyle intervention around pregnancy led to a "spill-over effect," including a healthier rate (kg/week) of maternal gestational weight gain, and infant growth during the first year. Study enrollment began in 2012, follow-up data collection completed in 2018, and the data were analyzed in 2019. The intervention focused on healthy maternal diet and physical activity but not pregnancy weight or infant feeding. Outcome data were abstracted from electronic medical records., Results: Of the 165 women who became pregnant, 114 enrolled in the nested cohort. The average pre-pregnancy BMI was 29.6 (SD 5.1) kg/m 2 . Mixed effects models suggested clinically insignificant differences in both the rate of gestational weight gain (-0.02 kg/week; 95% CI -0.09, 0.06) and the rate of infant growth (difference at 1 year: -0.002 kg/cm; 95% CI -0.009, 0.005)., Conclusions for Practice: A behavioral intervention that focused on overall maternal health delivered in the time around pregnancy did not result in a "spill-over effect" on healthy gestational weight gain or healthy infant growth during the first year of life., Trial Registration: This study is registered at www.clinicaltrials.gov NCT01316653.

The roles of SPRED proteins in signaling, development, and cancer are becoming increasingly recognized. SPRED proteins comprise an N-terminal EVH-1 domain, a central c-Kit-binding domain, and C-terminal SROUTY domain. They negatively regulate signaling from tyrosine kinases to the Ras-MAPK pathway. SPRED1 binds directly to both c-KIT and to the RasGAP, neurofibromin, whose function is completely dependent on this interaction. Loss-of-function mutations in SPRED1 occur in human cancers and cause the developmental disorder, Legius syndrome. Genetic ablation of SPRED genes in mice leads to behavioral problems, dwarfism, and multiple other phenotypes including increased risk of leukemia. In this review, we summarize and discuss biochemical, structural, and biological functions of these proteins including their roles in normal cell growth and differentiation and in human disease., (© 2020 Lorenzo and McCormick; Published by Cold Spring Harbor Laboratory Press.)

Maternal effects via hormonal transfer from the mother to the offspring provide a tool to translate environmental cues to the offspring. Experimental manipulations of maternally transferred hormones have yielded increasingly contradictory results, which may be explained by differential effects of hormones under different environmental contexts. Yet context-dependent effects have rarely been experimentally tested. We therefore studied whether maternally transferred thyroid hormones (THs) exert context-dependent effects on offspring survival and physiology by manipulating both egg TH levels and post-hatching nest temperature in wild pied flycatchers (Ficedula hypoleuca) using a full factorial design. We found no clear evidence for context-dependent effects of prenatal THs related to postnatal temperature on growth, survival and potential underlying physiological responses (plasma TH levels, oxidative stress and mitochondrial density). We conclude that future studies should test for other key environmental conditions, such as food availability, to understand potential context-dependent effects of maternally transmitted hormones on offspring, and their role in adapting to changing environments.

Early life adversity (ELA) increases risk for negative health outcomes, with sex disparities in prevalence and form of ELA experienced and risk for neuropsychiatric pathology. ELA comes in many forms (e.g. parental neglect/loss, limited access to resources) but whether disparate forms of ELA have common effects on outcomes, and if males and females are equally affected, remains unknown. Epidemiological studies often fail to accurately account for differences in type, timing, and duration of adversity experienced. Rodent models allow precise control of many of these variables. However, differences in the form of ELA, species, strain, housing, and testing paradigms used may contribute to differences in outcomes leading to questions of whether differences are the result of the form of ELA or these other variables. Here, we directly compared two mouse models of ELA, maternal separation (MS) and limited bedding (LB) in males and females on development of the body, motor and visual milestones, stress physiology, and anxiety-like behavior. LB affected timing of early milestones, somatic growth, and stress physiology in both sexes, yet only females showed later anxiety-like behaviors. MS rearing affected males and females similarly in early milestone development, yet only males showed changes in stress physiology and anxiety-like outcomes. These studies provide a platform to directly compare MS and LB models within one lab. The current work advances our understanding of the unique features of ELA that shape early neurodevelopmental events and risk for later pathology, increasing the translational relevance of these ELA models., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Because many threats exist in an animal's natural habitat, it is important to understand the impact of environmental challenges on maternal-offspring interactions and outcomes. In the current study, a rodent model incorporating the presence of restricted resources and an environmental threat (e.g. predator-related odors and sounds) was investigated. Specifically, pregnant females were assigned to one of four treatments: standard resources, without threat (SR; n = 7); standard resources plus threat (SR-T; n = 8); restricted resources, without threat (RR; n = 7); and restricted resources plus threat (RR-T; n = 6). Maternal rats were moved into the assigned conditions on postnatal day 2 and remained until pups were weaned. Following a standard pup retrieval task on postnatal days 2 and 6, maternal rats were exposed to a retrieval challenge task on postnatal day 8 in which each rat had to traverse a novel barrier to retrieve pups. For neurobiological measures of stress/resilience responsiveness, fecal samples were collected for detection of corticosterone and DHEA metabolites; additionally, immunohistochemistry was conducted on the maternal brains to indicate the presence of Neuropeptide Y (NPY) and Brain Derived Neurotrophic Factor (BDNF) immunoreactivity in the hippocampus, amygdala and hypothalamus. Pup development measures, including body weight and tail length, were also collected. Results suggest that maternal rats with restricted resources exhibited diminished maternal responsiveness that resulted in altered pup development measures; further, restricted resource rats exhibited endocrine markers of compromised emotional resilience (lower DHEA) and decreased neural markers of neuroplasticity (BDNF) and emotional resilience (NPY). Interestingly, predator threat affected various aspects of maternal-pup interactions but had no effect on neurobiological variables, suggesting that restricted resources had a more negative impact on maternal-related outcomes than the presence of predator threat., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: Much research on sanitation and linear growth in low- and middle-income countries focuses on children younger than 5 years. However, poor sanitation may be associated with growth faltering during middle and late childhood to a greater extent than previously recognized., Objective: To characterize the association of poor sanitation with height-for-age z (HAZ) scores in children and adolescents in India aged 0 to 18 years., Design, Setting, and Participants: This cross-sectional study examined 134 882 children and adolescents aged 0 to 18 years who were surveyed in the fourth round of India's District Level Household and Facilities Survey (survey conducted August 2012 to February 2014). Data were analyzed from June 1, 2019, to August 20, 2019., Exposures: Proportion of households reporting open defecation at the village level (to account for its high negative externality) and household-level access to boiled or filtered drinking water., Main Outcomes and Measures: Individual-level HAZ scores were measured in standard deviations. The association of exposures with outcomes was estimated using ordinary least-squares regression stratified by sex (boys and girls) and 4 age groups (≤1, >1 to ≤7, >7 to ≤12, >12 to ≤18 years). Models controlled for parental height and education, socioeconomic status, maternal age at birth, hemoglobin level, and indicators for state and birth year to adjust for regional (state) and temporal (birth year) fixed effects., Results: The sample comprised 70 463 male (52.5%) and 64 419 female (47.8%) children and adolescents aged 0 to 18 years; 46 722 participants (34.6%) were aged older than 12 to 18 years. Open defecation was inversely associated with HAZ score among all age groups except boys aged 1 year and younger (>1 to ≤7 years: β, -0.22; 95% CI, -0.35 to -0.10; >7 to ≤12 years: β, -0.15; 95% CI, -0.24 to -0.06; >12 to ≤18 years: β, -0.10; 95% CI, -0.19 to -0.01) and among girls aged between 7 and 18 years (>7 to ≤12 years: β, -0.22; 95% CI, -0.33 to -0.12; >12 to ≤18 years: β, -0.16; 95% CI, -0.23 to -0.09). Boiled or filtered drinking water was positively associated with HAZ score among younger girls (≤1 year: β, 0.26; 95% CI, 0.07 to 0.45; >1 to ≤7 years: β, 0.07; 95% CI, 0.01 to 0.14) and across all age groups in boys (≤1 years: β, 0.19; 95% CI, 0.03 to 0.35; >1 to ≤7 years: β, 0.07; 95% CI, 0.00 to 0.14; >7 to ≤12 years: β, 0.08; 95% CI, 0.03 to 0.13; >12 to ≤18 years: β, 0.06; 95% CI, 0.01 to 0.11)., Conclusions and Relevance: In this study, open defecation and lack of boiled or filtered drinking water were inversely associated with height-for-age measures across all ages in children and adolescents in India. Improved sanitation may benefit growth among children and adolescents older than 5 years.

Background: Developmental physiology can alter pharmacotherapy in preterm populations. Because of ethical and clinical constraints in studying this vulnerable age group, physiologically based pharmacokinetic models offer a viable alternative approach to predicting drug pharmacokinetics and pharmacodynamics in this population. However, such models require comprehensive information on the changes of anatomical, physiological and biochemical variables, where such data are not available in a single source., Objective: The objective of this study was to integrate the relevant physiological parameters required to build a physiologically based pharmacokinetic model for the preterm population., Methods: Published information on developmental preterm physiology and some drug-metabolising enzymes were collated and analysed. Equations were generated to describe the changes in parameter values during growth., Results: Data on organ size show different growth patterns that were quantified as functions of bodyweight to retain physiological variability and correlation. Protein binding data were quantified as functions of age as the body weight was not reported in the original articles. Ontogeny functions were derived for cytochrome P450 1A2, 3A4 and 2C9. Tissue composition values and how they change with age are limited., Conclusions: Despite the limitations identified in the availability of some tissue composition values, the data presented in this article provide an integrated resource of system parameters needed for building a preterm physiologically based pharmacokinetic model.

The induction of hematopoiesis in various cell types via transcription factor (TF) reprogramming has been demonstrated by several strategies. The eventual goal of these approaches is to generate a product for unmet needs in hematopoietic cell transplantation therapies. The most successful strategies hew closely to clues provided from developmental hematopoiesis in terms of factor expression and environmental cues. In this review, we aim to summarize the TFs that play important roles in developmental hematopoiesis primarily and to also touch on adult hematopoiesis. Several aspects of cellular and molecular biology coalesce in this process, with TFs and surrounding cellular signals playing a major role in the overall development of the hematopoietic lineage. We attempt to put these elements into the context of reprogramming and highlight their roles., (© 2019 New York Academy of Sciences.)

Sevoflurane is a widely used inhalational anesthetic in pediatric medicine that has been reported to have deleterious effects on the developing brain. Strategies to mitigate these detrimental effects are lacking. Sirtuin 2 (SIRT2) is a member of nicotinamide adenine dinucleotide (NAD + )-dependent protein deacetylases involved in a wide range of pathophysiological processes. SIRT2 inhibition has emerged as a promising treatment for an array of neurological disorders. However, the direct effects of SIRT2 on anesthesia-induced damage to the immature brain are unclear. Neonatal rats were exposed to 3% sevoflurane or 30% oxygen for 2 h daily with or without SIRT2 inhibitor AK7 pretreatment from postnatal day 7 (P7) to P9. One cohort of rats were euthanized 6, 12, and/or 24 h after the last gas exposure, and brain tissues were harvested for biochemical analysis and/or immunohistochemical examination. Cognitive functions were evaluated using the open field and Morris water maze tests on P25 and P28-32, respectively. SIRT2 was significantly up-regulated in neonatal rat hippocampus at 6 and 12 h post-anesthesia. Pretreatment with SIRT2 inhibitor AK7 reversed sevoflurane-induced hippocampus-dependent cognitive impairments. Furthermore, AK7 administration mitigated sevoflurane-induced neuroinflammation and microglial activation. Concomitantly, AK7 inhibited pro-inflammatory/M1-related markers and increased anti-inflammatory/M2-related markers in microglia. AK7 might prevent sevoflurane-induced neuroinflammation by switching microglia from the M1 to M2 phenotype. Downregulation of SIRT2 may be a novel therapeutic target for alleviating anesthesia-induced developmental neurotoxicity.

During pre-adolescence, several variables connected to growth and weight status could influence physical performance and technical skills. This study aims to assess the influence of growth-related anthropometric changes, weight status, and basketball experience on physical performance in pre-adolescent basketball players. The sample consisted of 50 male basketball players (12.2 ± 0.4 years-old) included in the U-13 category. Anthropometric characteristics were collected using standard procedures. Physical performance was evaluated by 20 m Dash, T-test, squat jump, countermovement jump, and medicine ball throw. In order to assess growth-related changes, we conducted two surveys within a 10-week time span. Student's t-test was used to compare the data collected in the two surveys and multiple regression analyses were performed to assess the effects of growth, weight status, and basketball experience on performance. After 10 weeks there was a significant increase in FFM (Fat-Free Mass) and a significant decrease in fat parameters. Moreover, between the two surveys, all motor tests significantly improved. The results of linear regression models showed that changes in %F (percentage of body fat) were significantly associated with speed and agility, while handgrip strength and weight status were associated with upper limb explosive strength. Basketball experience was a significant predictor of all three motor tests. In conclusion, body composition changes, years of experience, and weight status influenced physical performance and players' motor skills ability, especially speed, agility, and upper limb explosive strength.

Humans show marked variation in body size around the world, both within and among populations. At present, the tallest people in the world are from the Netherlands and the Balkan countries, while the shortest populations are central African Pygmies. There are genetic, genetic plasticity, developmental, and environmental bases for size variation in Homo sapiens from the recent past and the present. Early populations of Homo species also have shown considerable size variation. Populations from the present and the past are also marked by sexual dimorphism, which, itself, shows group variation. There is abundant evidence for the effects of limited food and disease on human growth and resultant adult body size. This environmental influence has been reflected in "secular trends" (over a span of years) in growth and adult size from socioeconomic prosperity or poverty (availability of resources). Selective and evolutionary advantages of small or large body size also have been documented. Heritability for human height is relatively great with current genome-wide association studies (GWAS) identifying hundreds of genes leading to causes of growth and adult size variation. There are also endocrinological pathways limiting growth. An example is the reduced tissue sensitivity to human growth hormone (HGH) and insulin-like growth factor (IGF-1) in Philippine and African hunter-gatherer populations. In several short-statured hunter-gatherer populations (Asian, African, and South American), it has been hypothesized that short life expectancy has selected for early maturity and truncated growth to enhance fertility. Some island populations of humans and other mammals are thought to have been selected for small size because of limited resources, especially protein. The high-protein content of milk as a staple food may contribute to tall stature in East African pastoral peoples. These and other evolutionary questions linked to life history, male competition, reproduction, and mobility are explored in this paper., (Copyright © 2020 Little.)

The purpose of this study was to examine the relationships between vocal pitch discrimination abilities and vocal responses to auditory pitch-shifts. Twenty children (6.6-11.7 years) and twenty adults (18-28 years) completed a listening task to determine auditory discrimination abilities to vocal fundamental frequency (f o ) as well as two vocalization tasks in which their perceived f o was modulated in real-time. These pitch-shifts were either unexpected, providing information on auditory feedback control, or sustained, providing information on sensorimotor adaptation. Children were subdivided into two groups based on their auditory pitch discrimination abilities; children within two standard deviations of the adult group were classified as having adult-like discrimination abilities (N = 11), whereas children outside of this range were classified as having less sensitive discrimination abilities than adults (N = 9). Children with less sensitive auditory pitch discrimination abilities had significantly larger vocal response magnitudes to unexpected pitch-shifts and significantly smaller vocal response magnitudes to sustained pitch-shifts. Children with less sensitive auditory pitch discrimination abilities may rely more on auditory feedback and thus may be less adept at updating their stored motor programs.

Primates develop slowly relative to their body size, a pattern posited to result from ecological risk aversion. Little is known, however, about how energy balance contributes to allostatic load in juveniles. Using data collected over 8 consecutive months, we examined variation in energy balance (as measured by urinary C-peptide) and how energy balance, life history status, and social competition related to allostatic load (as measured by deviation from baseline fecal glucocorticoid metabolites, dfGCs) in 41 wild juvenile blue monkeys from 3 social groups. Juvenile energy balance was higher among females, older juveniles, when ripe fruit was more available, and when rainfall was lower. Energy balance, but not life history or competitive environments, predicted dfGC concentrations, such that juveniles generally had lower mean dfGCs when they had higher energy balance. An additional exploratory analysis of how dfGCs relate to social strategies revealed that subjects had lower dfGCs when they groomed less, and played more. Time spent grooming interacted with energy balance in predicting dfGC concentrations, so that individuals that groomed more actually had higher dfGCs when they had higher energy balance. Together these results reveal that energetic deficiencies are a true ecological risk factor in blue monkeys, and suggest that navigating the social environment via overt affiliative behavior is potentially both a stress-relieving and stress-inducing endeavor during development., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hormones are largely responsible for the integrated communication of several physiological systems responsible for modulating cellular growth and development. Although the specific hormonal influence must be considered within the context of the entire endocrine system and its relationship with other physiological systems, three key hormones are considered the "anabolic giants" in cellular growth and repair: testosterone, the growth hormone superfamily, and the insulin-like growth factor (IGF) superfamily. In addition to these anabolic hormones, glucocorticoids, mainly cortisol must also be considered because of their profound opposing influence on human skeletal muscle anabolism in many instances. This review presents emerging research on: (1) Testosterone signaling pathways, responses, and adaptations to resistance training; (2) Growth hormone: presents new complexity with exercise stress; (3) Current perspectives on IGF-I and physiological adaptations and complexity these hormones as related to training; and (4) Glucocorticoid roles in integrated communication for anabolic/catabolic signaling. Specifically, the review describes (1) Testosterone as the primary anabolic hormone, with an anabolic influence largely dictated primarily by genomic and possible non-genomic signaling, satellite cell activation, interaction with other anabolic signaling pathways, upregulation or downregulation of the androgen receptor, and potential roles in co-activators and transcriptional activity; (2) Differential influences of growth hormones depending on the "type" of the hormone being assayed and the magnitude of the physiological stress; (3) The exquisite regulation of IGF-1 by a family of binding proteins (IGFBPs 1-6), which can either stimulate or inhibit biological action depending on binding; and (4) Circadian patterning and newly discovered variants of glucocorticoid isoforms largely dictating glucocorticoid sensitivity and catabolic, muscle sparing, or pathological influence. The downstream integrated anabolic and catabolic mechanisms of these hormones not only affect the ability of skeletal muscle to generate force; they also have implications for pharmaceutical treatments, aging, and prevalent chronic conditions such as metabolic syndrome, insulin resistance, and hypertension. Thus, advances in our understanding of hormones that impact anabolic: catabolic processes have relevance for athletes and the general population, alike., (Copyright © 2020 Kraemer, Ratamess, Hymer, Nindl and Fragala.)

Adolescence is a developmental period that is associated with physical, cognitive, and affective maturation and a time when sex biases in multiple psychiatric diseases emerge. While puberty onset marks the initiation of adolescence, it is unclear whether the pubertal rise in gonadal hormones generates sex differences in approach-avoidance behaviors that may impact psychiatric vulnerability. To examine the influence of pubertal development on adult behavior, we removed the gonads or performed sham surgery in male and female mice just prior to puberty onset and assessed performance in an odor-guided foraging task and anxiety-related behaviors in adulthood. We observed no significant sex differences in foraging or anxiety-related behaviors between intact adult male and female mice but found significant differences between adult male and female mice that had been gonadectomized (GDX) prior to puberty onset. GDX males failed to acquire the odor-guided foraging task, showed reduced locomotion, and exhibited increased anxiety-like behavior, while GDX females showed the opposite pattern of behavior. These data suggest that puberty may minimize rather than drive differences in approach-avoidance phenotypes in male and female mice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to determine the prevalence of poor iron status in young athletes throughout the stages of iron deficiency and assess sex differences with iron deficiency in relation to growth and development and dietary intake. Methods: A cross-sectional analysis evaluated young male and female athletes ( n  = 91) between the ages 8 and 16 years. Anthropometric assessments, body composition, dietary intakes, and blood samples measuring ferritin, soluble transferrin receptor (sTfR), and hemoglobin (Hb) were examined. Prevalence was calculated as percentages, and independent samples t tests examined sex differences. Pearson product-moment correlation coefficient analyses quantified relationships among variables for the composite sample and each sex separately. Results: Iron depletion (low ferritin) was present in 65% and 86%, low iron levels (sTfR) in 51% and 68%, and anemia (low Hb) in 46% and 53% of the males and females, respectively. As iron deficiency progressed from low ferritin to high sTfR to anemia, prevalence decreased in both sexes, but always remained higher in females. Males were greater than females for weight, arm muscle size, and ferritin concentrations, while females were greater than males for biological maturity ( p  ≤ 0.05). Dietary iron intake was moderately to highly correlated ( r  = 0.543-0.723, p  ≤ 0.05) with growth and development in females, but not males. Conclusions: Prevalence of poor iron status was higher than expected, particularly in adolescent females. Since rapid growth combined with sports participation may create high demands for iron bioavailability, emphasis may need to be placed on dietary iron intake for young athletes, particularly females.

Purpose: Gestational diabetes mellitus (GDM) and preeclampsia are leading causes of mortality and morbidity in mothers and children. High childhood body mass index (BMI) is among their myriad of negative outcomes. However, little is known about the trajectory of the child BMI exposed to GDM and co-occurring preeclampsia from early to mid-childhood. This study examined the independent and joint impact of GDM and preeclampsia on childhood BMI trajectory., Methods: A population-based sample of 356 mothers were recruited from OB/GYN clinics in New York. Their children were then followed annually from 18 to 72 months. Maternal GDM and preeclampsia status were obtained from medical records. Child BMI was calculated based on their height and weight at annual visits., Results: Hierarchical Linear Modeling was used to evaluate the trajectories of child BMI exposed to GDM and preeclampsia. BMI trajectory by GDM decreased (t ratio = - 2.24, [Formula: see text]0.45, 95% CI - 0.05-0.95, p = 0.07), but the trajectory by preeclampsia increased over time (t ratio = 3.153,[Formula: see text]0.65, 95% CI 0.11-1.18, p = 0.002). Moreover, there was a significant interaction between the two (t ratio = -2.24, [Formula: see text]- 1.244, 95% CI 0.15-2.33, p = 0.02), such that the BMI of children born to mothers with both GDM and preeclampsia showed consistent increases over time., Conclusions: GDM and preeclampsia could be used as a marker for childhood obesity risk and the identification of a high-risk group, providing potential early intervention. These findings highlight the importance of managing obstetric complications, as an effective method of child obesity prevention.

The multifunctional Ca 2+ /calmodulin-dependent protein kinase type 2 (CaMK-II) was first discovered in brain tissue and shown to have a central role in long term potentiation, responding to Ca 2+ elevations through voltage dependent channels. CaMK-II has a unique molecular mechanism that enables it to remain active in proportion to the degree (frequency and amplitude) of Ca 2+ elevations, long after such elevations have subsided. Ca 2+ is also a rapid activator of early development and CaMK-II is expressed and activated in early development. Using biochemical, pharmacological and genetic approaches, the functions of CaMK-II overlap remarkably well with those for Ca 2+ elevations, post-fertilization. Conclusion. Activated CaMK-II plays a central role in decoding Ca 2+ signals to activate specific events during early development; a majority of the known functions of elevated Ca 2+ act though CaMK-II.

Thyroid hormone (TH) signalling is a key modulator of fundamental biological processes that has been evolutionarily conserved in both vertebrate and invertebrate species. TH may have initially emerged as a nutrient signal to convey environmental information to organisms to induce morpho-anatomical changes that could maximise the exploitation of environmental resources, and eventually integrated into the machinery of gene regulation and energy production to become a key regulator of development and metabolism. As such, TH signalling is particularly sensitive to environmental stimuli, and its alterations result in fundamental changes in homeostasis and physiology. Stressful stimuli of various origins lead to changes in the TH-TH receptor (TR) axis in different adult mammalian organs that are associated with phenotypical changes in terminally differentiated cells, the reactivation of foetal development programmes, structural remodelling and pathological growth. Here, we discuss the evolution of TH signalling, review evolutionarily conserved functions of THs in essential biological processes, such as metamorphosis and perinatal development, and analyse the role of TH signalling in the phenotypical and morphological changes that occur after injury, repair and regeneration in adult mammalian organs. Finally, we examine the potential of TH treatment as a therapeutic strategy for improving organ structure and functions following injury.

Background: Physical fitness is strongly associated with health. Despite the extent of the nutritional transition from food scarcity to diets high in fats and refined carbohydrates that has occurred in China, to our knowledge, trends in physical fitness have not been described. We aimed to assess trends in physical fitness and its association with the nutritional transition among Chinese children and adolescents., Methods: In this retrospective analysis, data from Chinese school students aged 7-18 years were extracted from six successive national surveys undertaken between 1985 and 2014. Six components of physical fitness (forced vital capacity, standing long jump, sit-and-reach, body muscle strength, 50 m dash, and endurance running) were measured repeatedly in each survey and aggregated as a summary physical fitness indicator (PFI). Growth and nutritional status (stunting, thinness, normal weight, overweight, and obesity) were defined by use of WHO definitions, and we combined stunting and thinness as undernutrition and overweight and obesity as overnutrition. Urbanisation levels were obtained from the statistical yearbook of the National and Provincial Bureau of Statistics of China. We used fractional polynomial regression and generalised additive models to assess associations between PFI and nutritional outcomes and between PFI and levels of urbanisation., Findings: Between 1985 and 2014, 1 513 435 students participated in the Chinese National Survey on Students' Constitution and Health, and 1 494 485 were included in our study. We observed a decline of the PFI during 1985-2014 (overall PFI change -0·8), albeit with an increase from 1985 to 1995 (PFI change 1·2), coinciding with a shift in the major nutritional problems from stunting and thinness to overweight and obesity. Both undernourished (PFI -2·44 for thin and -3·42 for stunting) and overnourished (-1·49 for overweight and -3·63 for obese) students had a lower PFI than that of those with normal weight (-0·41) in 2014. Boys had a larger decline in PFI than girls in 1985-2014, especially boys with obesity (PFI change -2·7). We observed the highest PFI in 1995 (1·17), when the proportion of students with normal weight was highest. Advancing urbanisation was accompanied by declines in physical fitness, which occurred in both students in rural settings and those in urban settings in these regions., Interpretation: Our study supports the continuation of policies to improve physical fitness that focus on undernutrition, including economic subsidies, in poorer rural regions. However, for most of China, taxation of unhealthy foods, promotion of physical activity, reduction in academic pressures, promotion of dietary diversity, reduction of sedentary time, and engagement in formal sporting activities should be elements of policies to promote healthy weight status and prevent obesity in school students, which will also support physical fitness., Funding: National Natural Science Foundation, Humanities and Social Sciences Planning Fund Project, China Scholarship Council, and Innovation Fund for Outstanding Doctoral Candidates of Peking University Health Science Center., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Study Design: Retrospective comparative cohort study., Objective: To compare radiographic parameters between adolescents with a greater body mass index (BMI) percentile to underweight individuals., Summary of Background Data: Increased BMI percentile has been associated with increased complications after surgical correction of adolescent idiopathic scoliosis (AIS). However, association between BMI percentile and preoperative sagittal plane alignment has not been evaluated. The purpose of this study was to evaluate the effect of BMI percentile on sagittal alignment in AIS patients compared with nonscoliotic adolescents., Methods: Posterior-anterior and lateral spinal radiographs of 1,551 AIS patients with a thoracic major curve (Lenke 1-4) and 70 nonscoliotic adolescent patients were compared. BMI percentile was determined based on age and sex, and patients were divided into four categories: underweight (<5th percentile), normal-weight (5th-85th percentile), overweight (85th-95th percentile), and obese (≥95th percentile)., Results: Coronal plane deformity magnitude was not significantly different between the 4 categories of AIS patients (p = .51). Increased BMI percentile was associated with increased thoracic kyphosis globally (T2-T12: p < .005) as well as segmentally (T2-T5: p < .001; T5-T12: p < .001) in patients with AIS. This was also true in obese adolescents without spinal deformity (p < .04). Lumbar lordosis, pelvic incidence, and pelvic tilt were not significantly different between AIS patients in the four BMI percentile categories (p > .07). Pelvic incidence was significantly greater in AIS patients compared with nonscoliotic adolescents (54 ± 13 vs. 46 ± 11; p = .01)., Conclusion: Increased BMI percentile is associated with increased thoracic kyphosis in AIS patients and nonscoliotic adolescents. Excess weight may reduce anterior vertebral growth. AIS patients have an increased pelvic incidence compared with nonscoliotic adolescents; however, this variable is not influenced by body mass. These relationships should be taken into account when planning sagittal plane deformity correction or considering neuro axis disorders (also associated with increased kyphosis) in patients with scoliosis., Level of Evidence: Level II., (Copyright © 2019 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Study Design: Retrospective case series., Objectives: To develop normative data of pulmonary function tests (PFTs) and radiographic measures of chest development in normal children and to determine if the prior proposed T1-T12 height of 22 cm for spinal fusion in a growing child is adequate for pulmonary function based on normative PFT values at skeletal maturity., Summary of Background Data: Shortening of the spine from T1-T12 is a concern with early thoracic fusion for spinal deformity, as it has a deleterious effect on the development of the pulmonary system., Methods: Children with mild asthma who had pulmonary function tests (PFTs) >90% and without chest or spinal deformity were identified. PFT data included absolute forced vital capacity (FVC), %-predicted FVC, absolute forced expiratory volume in one second (FEV1), %-predicted FEV1, and FEV1/FVC. Radiographic measurements performed on chest radiographs included T1-T12 height, coronal chest width (CCW), and space available for the lung (SAL) bilaterally. These data were analyzed for all patients and for patients with T1-T12 heights 22-24 cm. To assess the impact of T1-T12 shortening on PFTs at skeletal maturity, spirometric standards for healthy adult lifetime nonsmokers were used., Results: Of 1,797 PFT studies, 149 children (average age 12.4 ± 3.0 years; girls, 97) were analyzed. For the entire cohort, PFT values were as follows: FVC 3.0 ± 0.9 L, %-predicted FVC 103.9% ± 10.6%, absolute FEV1 2.7 ± 0.9 L, %-predicted FEV1 106.9% ± 11.1%, and FEV1/FVC 90.7% ± 2.6%. The averages for T1-T12 height was 25.6 ± 3.8 cm, CCW 25.5 ± 3.4 cm, and SAL bilaterally 19.0 ± 3.5 cm. For the 21 patients (girls 11; average age 9.7 ± 1.4 years) with T1-T12 heights 22-24 cm, absolute FVC was 2.2 ± 0.3 L, %-predicted FVC was 104.0% ± 13.0%, absolute FEV1 was 2.0 ± 0.3 L, %-predicted FEV1 was 108.2% ± 15.0%, and FEV1/FVC was 91.0% ± 2.7%. If these kids with 22-24 cm T1-T12 heights maintained the same thoracic height, they were calculated to have %-predicted FVC of 44% (girl) and 42% (boy) and %-predicted FEV1 of 42% (girl) and 43% (boy) at skeletal maturity (15 years old)., Conclusions: Percent-predicted FEV1 and FVC values for normal children with a T1-T12 height of 22 cm at skeletal maturity were <50%. Though this analysis does not take into consideration radial expansion of the chest or children with scoliosis (idiopathic, congenital, neuromuscular), these values are concerning and may not be adequate to guarantee that children with early-onset scoliosis who are fused with T1-T12 heights of 22 cm will have an asymptomatic pulmonary status in adulthood., Level of Evidence: Level IV., (Copyright © 2019 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Scaling laws relating body mass to species characteristics are among the most universal quantitative patterns in biology. Within major taxonomic groups, the 4 key ecological variables of metabolism, abundance, growth, and mortality are often well described by power laws with exponents near 3/4 or related to that value, a commonality often attributed to biophysical constraints on metabolism. However, metabolic scaling theories remain widely debated, and the links among the 4 variables have never been formally tested across the full domain of eukaryote life, to which prevailing theory applies. Here we present datasets of unprecedented scope to examine these 4 scaling laws across all eukaryotes and link them to test whether their combinations support theoretical expectations. We find that metabolism and abundance scale with body size in a remarkably reciprocal fashion, with exponents near ±3/4 within groups, as expected from metabolic theory, but with exponents near ±1 across all groups. This reciprocal scaling supports "energetic equivalence" across eukaryotes, which hypothesizes that the partitioning of energy in space across species does not vary significantly with body size. In contrast, growth and mortality rates scale similarly both within and across groups, with exponents of ±1/4. These findings are inconsistent with a metabolic basis for growth and mortality scaling across eukaryotes. We propose that rather than limiting growth, metabolism adjusts to the needs of growth within major groups, and that growth dynamics may offer a viable theoretical basis to biological scaling., Competing Interests: The authors declare no competing interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Introduction: In the dentate gyrus of the rodent hippocampus, neurogenesis begins prenatally and continues to the end of life. Adult-born neurons often die in the first few weeks after mitosis, but those that survive to 1 month persist indefinitely. In contrast, neurons born at the peak of development are initially stable but can die later in adulthood. Physiological and pathological changes in the hippocampus may therefore result from both the addition of new neurons and the loss of older neurons. The extent of neuronal loss remains unclear since no studies have examined whether neurons born at other stages of development also undergo delayed cell death., Methods: We used BrdU to label dentate granule cells that were born in male rats on embryonic day 19 (E19; before the developmental peak), postnatal day 6 (P6; peak), and P21 (after the peak). We quantified BrdU + neurons in separate groups of rats at 2 and 6 months post-BrdU injection to estimate cell death in young adulthood., Results: Consistent with previous work, there was a 15% loss of P6-born neurons between 2 and 6 months of age. In contrast, E19- or P21-born neurons were stable throughout young adulthood., Discussion: Delayed death of P6-born neurons suggests these cells may play a unique role in hippocampal plasticity adulthood, for example, by contributing to the turnover of hippocampal memory. Their loss may also play a role in disorders that are characterized by hippocampal atrophy., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Objectives: Evidence suggests that maternal psychological distress is an under-diagnosed condition that can have lasting impacts on child outcomes. Models based solely on maternal outcomes have not found screening to be cost-effective. This research explores the effects of self-reported maternal psychological distress on children's language and behavioural development up to the age of 7., Methods: Using longitudinal survey data from 10,893 families in the UK Millennium Cohort Study, multilevel models are used to explore the differential effects of maternal diagnosed and treated depression versus untreated maternal psychological distress during the postnatal year on longer-term child outcomes., Results: Both diagnosed and treated depression and self-reported maternal psychological distress have detrimental effects on child behavioural development. Behavioural outcomes up to age 5 were better for children of women who received treatment for depression, compared with children those whose mothers' psychological distress was untreated, but this was not maintained to age 7. Little or no evidence of a difference was found between maternal psychological distress and child language development., Conclusions for Practice: This research highlights the lack of effectiveness of existing treatment for maternal psychological distress both to benefit child development and to provide long-term symptom remediation for women. Future research could aim to identify more effective treatments for both women and children.