Children with idiopathic short stature have significantly different gut microbiota than their normal height siblings: a case-control study.

Objectives: To investigate the role of gut microbiota (GM) in pathogenesis of idiopathic short stature (ISS) by comparing GM of ISS children to their normal-height siblings.

Methods: This case-control study, conducted at the Schneider Children's Medical Center's Institute for Endocrinology and Diabetes between 4/2018-11/2020, involved 30 pairs of healthy pre-pubertal siblings aged 3-10 years, each comprising one sibling with ISS and one with normal height. Outcome measures from fecal analysis of both siblings included GM composition analyzed by 16S rRNA sequencing, fecal metabolomics, and monitoring the growth of germ-free (GF) mice after fecal transplantation.

A Whey-Based Diet Can Ameliorate the Effects of LPS-Induced Growth Attenuation in Young Rats.

Chronic inflammation in childhood is associated with impaired growth. In the current study, a lipopolysaccharide (LPS) model of inflammation in young rats was used to study the efficacy of whey-based as compared to soy-based diets to ameliorate growth attenuation. Young rats were injected with LPS and fed normal chow or diets containing whey or soy as the sole protein source during treatment, or during the recovery period in a separate set of experiments.

Different Effects of Soy and Whey on Linear Bone Growth and Growth Pattern in Young Male Sprague-Dawley Rats.

The aim of this investigation was to determine the better protein for supporting optimal linear growth, as the exact composition and benefits of specific dietary proteins in supporting linear growth is unknown. In the current study, we compared the effect of soy and whey proteins, both proteins contain all essential amino acids and are considered the best proteins in their categories. Young male rats were subjected to multiple feeding protocols using iso-energetic diets containing soy or whey as the sole protein source.

Anxiety and Cognition in Cre- Collagen Type II Sirt1 K/O Male Mice.

Introduction: Using transgenic collagen type II-specific Sirt1 knockout (CKO) mice we studied the role of Sirt1 in nutritional induced catch up growth (CUG) and we found that these mice have a less organized growth plate and reduced efficiency of CUG. In addition, we noted that they weigh more than control (CTL) mice. Studying the reason for the increased weigh, we found differences in activity and brain function.

Associations of Obesity with Linear Growth and Puberty.

Background: The prevalence of obesity in childhood has increased dramatically in recent decades with increased risk of developing cardiometabolic and other comorbidities. Childhood adiposity may also influence processes of growth and puberty.

Summary: Growth patterns of obesity during childhood have been shown to be associated with increased linear growth in early childhood, leading to accelerated epiphyseal growth plate (EGP) maturation.

Cartilage -specific knockout of Sirt1 significantly reduces bone quality and catch-up growth efficiency.

Background: Spontaneous catch-up (CU) growth occurs when a growth-restricting factor is resolved. However, its efficiency is sometimes inadequate and growth deficits remain permanent. The therapeutic toolbox for short stature is currently very limited, thus, finding new regulatory pathways is important for the development of novel means of treatment.

Growth hormone therapy in children with idiopathic short stature - the effect on appetite and appetite-regulating hormones: a pilot study.

Aim: To investigate the effect of growth hormone (GH) therapy on appetite-regulating hormones and to examine the association between these hormones and the response to GH, body composition, and resting energy expenditure (REE).

Methods: Nine pre-pubertal children with idiopathic short stature underwent a standard meal test before and 4 months following initiation of GH treatment. Ghrelin, GLP-1, leptin, and insulin levels were measured; area under the curve (AUC) was calculated.

The association between adipocytokines and glycemic control in women with gestational diabetes mellitus.

To evaluate the relationship between adipocytokines and glycemic control. Prospective observational trial of gestations with gestational diabetes mellitus (GDM). Fasting glucose (FG), insulin, adiponectin, leptin, chemerin, retinol-binding protein 4 (RBP-4), osteocalcin, and resistin were measured.

Leptin stimulates aromatase in the growth plate: limiting catch-up growth efficiency.

Catch-up growth (CUG) in childhood is defined as periods of growth acceleration, after the resolution of growth attenuation causes, bringing the children back to their original growth trajectory. Sometimes, however, CUG is incomplete, leading to permanent growth deficit and short stature. The aim of this study was to investigate the mechanisms that limit nutritional-CUG.

The unique clinical spectrum of maturity onset diabetes of the young type 3.

Phenotypic variability in maturity-onset diabetes of the young (MODY) makes screening criteria for genomic analysis challenging. We describe the clinical spectrum in a large pedigree with HNF1A-MODY; as generations progressed, the course and outcome became poorer. Although uncommon, pancreatic autoantibodies and diabetes ketoacidosis should not exclude the diagnosis of MODY.

Food restriction followed by refeeding with a casein- or whey-based diet differentially affects the gut microbiota of pre-pubertal male rats.

Researchers are gaining an increasing understanding of host-gut microbiota interactions, but studies of the role of gut microbiota in linear growth are scarce. The aim of this study was to investigate the effect of food restriction and refeeding with different diets on gut microbiota composition in fast-growing rats. Young male Sprague-Dawley rats were fed regular rat chow ad libitum (control group) or subjected to 40% food restriction for 36 days followed by continued restriction or ad libitum refeeding for 24 days.

Beta Palmitate Improves Bone Length and Quality during Catch-Up Growth in Young Rats.

Palmitic acid (PA) is the most abundant saturated fatty acid in human milk, where it is heavily concentrated in the --position (termed beta palmitate, BPA) and as such is conserved in all women, regardless of their diet or ethnicity, indicating its physiological and metabolic importance. We hypothesized that BPA improves the efficiency of nutrition-induced catch up growth as compared to - PA, which is present in vegetable oil. Pre-pubertal male rats were subjected to a 17 days food restriction followed by re-feeding for nine days with PA or BPA-containing diets.

The reliability, concurrent validity and association with salivary oxytocin of the self-report version of the Inventory of Callous-Unemotional Traits in adolescents with conduct disorder.

The present study evaluated the self-report version of the Inventory of Callous-Unemotional Traits (ICU-SR) in terms of reliability, concurrent validity, and correlation with salivary oxytocin levels, a potential biomarker of CU traits. 67 socially at-risk male adolescents (mean 16.2 years) completed the ICU-SR, ICU teacher-version (ICU-TR), Strengths and Difficulties Questionnaire, and their medical files were coded for previous antisocial acts using Brown-Goodwin Lifetime Aggression Scale.

Which dietary components modulate longitudinal growth?

Purpose Of Review: Linear growth in children is sensitive to nutritional status; the growth of the human skeleton requires many different nutritional factors for energy and building blocks: proteins, lipids, carbohydrates and micronutrients. However, what are the specific nutritional factors that are required for proper growth and what is the composition that will be most beneficial is still not known.

Recent Findings: Recent findings indicate that macro and micronutrients are required as building blocks and as cofactors for important enzymes.

Effect of Nutrition on Statural Growth .

In children, proper growth and development are often regarded as a surrogate marker for good health. A complex system controls the initiation, rate, and cessation of growth, and thus gives a wonderful example of the interactions between genetics, epigenetics, and environmental factors (especially stress and nutrition). Malnutrition is considered a leading cause of growth attenuation in children.

How Milk and Its Proteins Affect Growth, Bone Health, and Weight .

Milk has long been recognized to constitute a complete, well-balanced source of the nutrients and energy required to ensure the proper postnatal growth and development of infants. A growing body of evidence suggests the positive effects of dairy products and particularly of milk proteins on linear growth also in older children, both healthy or during recovery from malnutrition. This evidence led the way to the performance of extensive research aimed to delineate the components of milk and the mechanisms acting to make milk so effective.

Quantitative proteomics of rat livers shows that unrestricted feeding is stressful for proteostasis with implications on life span.

Studies in young mammals on the molecular effects of food restriction leading to prolong adult life are scares. Here, we used high-throughput quantitative proteomic analysis of whole rat livers to address the molecular basis for growth arrest and the apparent life-prolonging phenotype of the food restriction regimen. Over 1800 common proteins were significantly quantified in livers of ad libitum, restriction- and re-fed rats, which summed up into 92% of the total protein mass of the cells.

Skeletal effect of casein and whey protein intake during catch-up growth in young male Sprague-Dawley rats.

The aim of the present study was to determine whether the type of protein ingested influences the efficiency of catch-up (CU) growth and bone quality in fast-growing male rats. Young male Sprague-Dawley rats were either fed ad libitum (controls) or subjected to 36 d of 40 % food restriction followed by 24 or 40 d of re-feeding with either standard rat chow or iso-energetic, iso-protein diets containing milk proteins - casein or whey. In terms of body weight, CU growth was incomplete in all study groups.

Growth attenuation is associated with histone deacetylase 10-induced autophagy in the liver.

Our previous data suggested that the histone deacetylase (HDAC) SIRT1 is involved in mediating the effect of nutrition on growth. The aim of the present research was to study the mechanism by which additional HDACs may be involved in nutrition-induced linear growth. The in vivo studies were performed in young male Sprague-Dawley rats that were either fed ad libitum (AL) or subjected to 10days of 40% food restriction (RES) and then refed (CU).

Salivary oxytocin in adolescents with conduct problems and callous-unemotional traits.

Callous-unemotional (CU) traits correlate with the severity and prognosis of conduct disorder in youth. The neuropeptide oxytocin (OT) has been linked to prosocial behaviors, including empathy and collaboration with others. This study discusses a possible role for OT in the biology of delinquent behavior.

Growth without growth hormone: can growth and differentiation factor 5 be the mediator?

Growth without growth hormone (GH) is often observed in the setup of obesity; however, the missing link between adipocytes and linear growth was until now not identified. 3T3L1 cells were induced to differentiate into adipocytes and their conditioned medium (CM) (adipocytes CM, CMA) was added to metatarsals bone culture and compared to CM derived from undifferentiated cells. CMA significantly increased metatarsals bone elongation.

Low Frequencies of Autoimmunity-Associated PTPN22 Polymorphisms in MODY Patients, Including Those Transiently Expressing Islet Cell Autoantibodies.

Background: The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid tyrosine phosphatase (LYP), which is expressed primarily in lymphoid tissues. The functional but geographically highly variable PTPN22 single-nucleotide polymorphisms (SNPs), particularly c.1858C>T, contribute to the onset and progression of autoimmunity-associated diseases and facilitate the expression of disease-associated autoantibodies.

Nutritionally-induced catch-up growth.

Malnutrition is considered a leading cause of growth attenuation in children. When food is replenished, spontaneous catch-up (CU) growth usually occurs, bringing the child back to its original growth trajectory. However, in some cases, the CU growth is not complete, leading to a permanent growth deficit.

Vascular endothelial growth factor (VEGF) levels in short, GH treated children: a distinct pattern of VEGF-C in Noonan syndrome.

Context: Noonan syndrome (NS) is characterized by short stature and elevated risk of lymphedema. The mechanism underlying lymphedema may be mediated by vascular endothelial growth factors (VEGFs).

Objective: To assess the effect of growth hormone (GH) treatment on plasma insulin-like growth factor (IGF)-1, VEGF-A and VEGF-C levels in patients with NS as compared to short GH-sufficient children.

A novel MKRN3 missense mutation causing familial precocious puberty.

Central precocious puberty may be familial in about a quarter of the idiopathic cases. However, little is known about the genetic causes responsible for the disorder. In this report we describe a family with central precocious puberty associated with a mutation in the makorin RING-finger protein 3 (MKRN3) gene.