BACKGROUND: There is no appropriate tool to predict recombinant human growth hormone (rhGH) response before therapy initiation in short-stature children in late puberty. The current study aimed to explore the associations between magnetic resonance imaging (MRI) stages of the knee growth plates and rhGH response in short-stature children in late puberty.
METHODS: In this prospective cohort study, short-stature children in late puberty were treated with rhGH and followed up for 6 months. We proposed a novel knee MRI staging system according to the growth plate states of distal femurs or proximal tibias and divided the participants into three groups: unclosed growth plate group, marginally closed growth plate group, and nearly closed growth plate group. The primary outcomes were height gain and growth velocity (GV), which were assessed three months later.
RESULTS: Fifty participants were enrolled, including 23 boys and 27 girls. GV and height gain after 6 months of rhGH therapy decreased successively in the three groups with an increased degree of growth plate fusion, especially when grouped by proximal tibias (GV1-3 mon from 9.38 to 6.08 to 4.56 cm/year, GV4-6 mon from 6.75 to 4.92 to 3.25 cm/year, and height gain from 4.03 to 2.75 to 1.95 cm, all P < 0.001). Moreover, the MRI stages of growth plates independently served as a significant variable for GV and height gain after therapy, especially when grouped by proximal tibias (all P < 0.01).
CONCLUSIONS: The MRI staging method is expected to be an effective tool for predicting rhGH response before therapy initiation in short-stature children in late puberty.

To investigate the effectiveness and safety of gonadotropin-releasing hormone analogue (GnRHa) in combination with recombinant human growth hormone (rhGH) in girls with central precocious puberty (CPP).
Clinical data of 80 girls diagnosed with idiopathic central precocious puberty (ICPP) between January 2017 and June 2021 were retrospectively analyzed. Treatment strategy involved GnRHa alone (group A: n=34) and GnRHa+rhGH (group B: n=46). Children\'s heights (Ht), weights (Wt) and sex hormone levels were measured every 3 months after treatment and bone age (BA) every six months. Heights, growth velocity (GV), predicted adult height (PAH), weights, body mass index (BMI), sex hormone levels and bone age were compared between the two groups.
Children in group B showed greater height gain at the 12th, 24th and 30th months after treatment (p<0.05) than those in group A, had faster growth rates in the first and second year following treatment (p<0.05) and better PAH (p<0.05). No statistical differences in weight or BMI were found between the two groups before treatment or at any time after treatment (p>0.05). Levels of LH and FSH were lower in both groups after treatment with no statistical differences between groups (p>0.05). The gap between bone age and chronological age gradually decreased in both groups and no abnormal progression of bone age or other adverse side effects occurred.
The combination of GnRHa with rhGH produced better height gains than GnRHa alone for patients with CPP. The gonadal axis was suppressed and progression of bone age delayed with good safety and efficacy.

Child growth impairments are rampant in sub-Saharan Africa. To combat this important health problem, long-term follow-up studies are needed to examine possible benefits and sustainability of various interventions designed to correct inadequate child growth. Our aim was to perform a follow-up study of children aged 60-72 months whose mothers participated in a two-armed cluster-randomized education intervention trial lasting 6 months in rural Uganda when their children were 6-8 months old with data collection at 20-24 and at 36 months. The education focused on nutrition, hygiene, and child stimulation.
We measured growth using anthropometry converted to z-scores according to WHO guidelines. We also included assessments of body composition using bioimpedance. We used multilevel mixed effect linear regression models with maximum likelihood method, unstructured variance-covariance structure, and the cluster as a random effect component to compare data from the intervention (receiving the education and routine health care) with the control group (receiving only routine health care).
Of the 511 children included in the original trial, data from 166/263 (63%) and 141/248 (57%) of the children in the intervention and control group, respectively, were available for the current follow-up study. We found no significant differences in any anthropometrical z-score between the two study groups at child age of 60-72 months, except that children in the intervention group had lower (P = 0.006) weight-for-height z-score than the controls. There were no significant differences in the trajectories of z-scores or height growth velocity (cm/year) from baseline (start of original trial) to child age of 60-72 months. Neither did we detect any significant difference between the intervention and control group regarding body composition (fat mass, fat free mass, and total body water) at child age 60-72 months. Separate gender analyses had no significant impact on any of the growth or body composition findings.
In this long-term study of children participating in a randomized maternal education trial, we found no significant impact of the intervention on anthropometrical z-scores, height growth velocity or body composition.
Clinical Trials (clinical trials.gov) ClinicalTrials.gov ID NCT02098031.

OBJECTIVE: To study the effect of recombinant human growth hormone (rhGH) treatment on the growth velocities and serum index expressions of short stature children.
METHODS: 56 short stature children admitted to our hospital from January 2018 to January 2020 were recruited as the study cohort. All the children were treated with rhGH. After six months of treatment, their serum indicators [ghrelin, Nesfatin-1, bone-specific alkaline phosphate (BAP), insulin-like growth factor 1 (IGF-1)], their growth velocity indicators [body mass index (BMI), height, growth velocity (GV)], their blood lipid levels [triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), high and low density lipoprotein (HDL)], their insulin statuses [fasting insulin (FINS), their homeostasis model assessment of insulin resistance (HOMA-IR)], and their thyroid function index [thyroid stimulating hormone (TSH), 3\'-triiodothyronine (T3), 4\'-triiodothyronine (T4)] level changes before and after the treatment were compared.
RESULTS: (1) After the treatment, the children\'s serum ghrelin and IGF-1 levels increased in comparison with their pre-treatment levels (P<0.05), and their nesfatin-1 levels decreased (P<0.05). (2) After the treatment, the children\'s BMI, height, and GV increased in comparison with their pre-treatment levels (P<0.05). (3) After the treatment, the children\'s TG levels were noticeably higher than they were before the treatment (P<0.05), and the TC and LDL levels were remarkably lower than they were before the treatment (P<0.05). (4) After the treatment, the children\'s T3 and T4 levels were significantly higher compared to their levels before the treatment (P<0.05).
CONCLUSIONS: GH can promote the development and growth of short stature children, improve their related serum indicator levels, and does not induce metabolic dysfunction.

A yeast deletion mutation in the nuclear-encoded gene, AFO1, which codes for a mitochondrial ribosomal protein, led to slow growth on glucose, the inability to grow on glycerol or ethanol, and loss of mitochondrial DNA and respiration. We noticed that afo1- yeast readily obtains secondary mutations that suppress aspects of this phenotype, including its growth defect. We characterized and identified a dominant missense suppressor mutation in the ATP3 gene. Comparing isogenic slowly growing rho-zero and rapidly growing suppressed afo1- strains under carefully controlled fermentation conditions showed that energy charge was not significantly different between strains and was not causal for the observed growth properties. Surprisingly, in a wild-type background, the dominant suppressor allele of ATP3 still allowed respiratory growth but increased the petite frequency. Similarly, a slow-growing respiratory deficient afo1- strain displayed an about twofold increase in spontaneous frequency of point mutations (comparable to the rho-zero strain) while the suppressed strain showed mutation frequency comparable to the respiratory-competent WT strain. We conclude, that phenotypes that result from afo1- are mostly explained by rapidly emerging mutations that compensate for the slow growth that typically follows respiratory deficiency.

The present study aimed to compare the efficacy and safety of recombinant human growth hormone (rhGH) therapy between children with idiopathic short stature (ISS) and growth hormone deficiency (GHD).
A total of 150 pediatric patients with ISS and 153 pediatric patients with GHD who received rhGH treatment for more than one year from 2005 to 2016 were enrolled. Growth velocity (GV); height standard deviation (HtSD); insulin-like growth factor-1 standard deviation (IGF-1SD); body mass index (BMI); and the incidence of fasting hyperglycemia, fasting hyperinsulinemia, and hypothyroidism were recorded and compared.
At the beginning of treatment, chronological age, bone age, height, and BMI were not statistically significant between the two groups. rhGH dosage in ISS was significantly higher compared with GHD (P = 0). GV from half a year to three years after rhGH therapy was higher in the GHD group compared with the ISS group, but the differences were not statistically significant (P > 0 .05). HtSD increased in the two groups after rhGH therapy. HtSD at the beginning and after three years of therapy was not different between groups except for after half a year of therapy. HtSD in patients with ISS was significantly higher compared with GHD (P < 0 .05). The incidence of hypothyroidism was significantly higher in the GHD group compared with the ISS group (13.72% vs. 6.0%; P < 0.05). Moreover, the incidence of hyperinsulinemia was significantly higher in the ISS group compared with the GHD group (15.33% vs. 7.84%; P < 0 .05).
rhGH increases growth in children with ISS and GHD. Fasting insulin and thyroid function were closely monitored for long-term follow up.

Necrotizing Enterocolitis (NEC) is associated with prematurity, enteral feedings, and enteral dysbiosis. Accordingly, we hypothesized that along with nutritional variability, metabolic dysfunction would be associated with NEC onset. Methods: We queried a multicenter longitudinal database that included 995 preterm infants (<32 weeks gestation) and included 73 cases of NEC. Dried blood spot samples were obtained on day of life 1, 7, 28, and 42. Metabolite data from each time point included 72 amino acid (AA) and acylcarnitine (AC) measures. Nutrition data were averaged at each of the same time points. Odds ratios and 95% confidence intervals were calculated using samples obtained prior to NEC diagnosis and adjusted for potential confounding variables. Nutritional and metabolic data were plotted longitudinally to determine relationship to NEC onset. Results: Day 1 analyte levels of alanine, phenylalanine, free carnitine, C16, arginine, C14:1/C16, and citrulline/phenylalanine were associated with the subsequent development of NEC. Over time, differences in individual analyte levels associated with NEC onset shifted from predominantly AAs at birth to predominantly ACs by day 42. Subjects who developed NEC received significantly lower weight-adjusted total calories (p < 0.001) overall, a trend that emerged by day of life 7 (p = 0.020), and persisted until day of life 28 (p < 0.001) and 42 (p < 0.001). Conclusion: Premature infants demonstrate metabolic differences at birth. Metabolite abnormalities progress in parallel to significant differences in nutritional delivery signifying metabolic dysfunction in premature newborns prior to NEC onset. These observations provide new insights to potential contributing pathophysiology of NEC and opportunity for clinical care-based prevention.

The aim was to assess growth velocity (GV) during human recombinant growth hormone (hGH) treatment of children with multiple pituitary hormone deficiency (MPHD) caused by pituitary stalk interruption syndrome (PSIS) and to analyze the characteristics of patients that attained normal adult heights.
Data from 74 (16 female) children with MPHD caused by PSIS with GH, thyroid stimulating hormone, gonadotropin and adrenocorticotropic hormone deficiencies were collected. Subjects were divided into groups: 12 pre-pubescent females (Female-Group) and 36 pre-pubescent males (Male-Group 1). The remaining 22 males were further sub-divided into two groups (Male-Group 2 and Male-Group 3) according to the initiation of gonadotropin replacement treatment, based on bone age and height.
No differences in change in height standard deviation score (△HtSDS) and GV were observed at different time points of hGH treatment between the Female-Group and Male-Group 1 (p>0.05). GV was significantly greater in the first year of hGH therapy than in subsequent years: Female-Group p=0.011; Male-Group 1 p<0.001; Male-Group 2 p=0.005; and Male-Group 3 p=0.046. Adult height was achieved by 23 (19 males and 4 females) patients. The total gain in height positively correlated with the GV during the first year (r=0.626, p<0.001).
GV during hGH treatment were similar amongst pre-pubescent males and females with MPHD caused by PSIS. GV during the first year of hGH treatment appears to be an effective predictor of final height in patients with MPHD caused by PSIS.

BACKGROUND: Optimum early postnatal growth is critical for early and later health of preterm infants. Postnatal length and weight growth velocities and their associated perinatal factors in healthy late preterm infants without restriction of neonatal complications and nutritional problems have not been widely studied.
METHODS: As part of ongoing longitudinal follow-up study of growth and development of preterm infants in Shandong Qianfoshan Hospital in China, 599 healthy late preterm infants without neonatal complications and nutritional problems were sampled from 795 preterm infants born in January 2014 to April 2017. Perinatal factors, growth parameters, growth velocities(ΔLengthZ and ΔWeightZ: Z-score changes of length and weight) during birth and term-corrected age were documented. Associated variables of growth velocities were analyzed by bivariate and multivariate regression analyses. Adjusted ΔLengthZ and ΔWeightZ were compared between/among subgroups of associated variables using analysis of covariance. Catch-up growth were defined as ΔLengthZ or ΔWeightZ > 0.67.
RESULTS: The mean ΔLengthZ and ΔWeightZ were 0.28, 0.65, respectively. Catch-up growth of length and weight was ubiquitous(30.7, 46.2%, respectively). Faster length growth velocity was associated with male, larger postmenstrual age(PMA) at birth, younger mother and larger PMA at visit; Faster weight growth velocity was associated with male, unfavorable intrauterine growth status defined by birth weight percentile(Small-for-Gestational-Age(P90)), twin and larger PMA at visit. When adjusted for associated co-variables, weight catch-up growth existed in subgroups of 36 weeks PMA at birth, male, twin and SGA, while AGA almost reached this standard with mean adjusted ΔWeightZ as 0.66. Although none of these subgroups got length catch-up growth standard, infants of 36 weeks PMA at birth had statistically rapider length growth velocity than 34 and 35 weeks PMA at birth subgroups(mean adjusted ΔLengthZs of 34, 35 and 36 weeks subgroups: 0.10, 0.22, 0.38, respectively).
CONCLUSIONS: Postnatal length and weight growth velocities of healthy late preterm infants from birth to term-corrected age were much superior than that of Fenton reference, especially for weight, with ubiquitous catch-up growth. Different associated factors for length and weight growth signified the necessity of constructing more detailed growth standards by specific stratification for associated factors.

A model for free growth of a lamellar eutectic dendrite with an incident flow was proposed for the breakdown of a planar solid/liquid interface into a dendritic contour due to a negative thermal gradient in an undercooled liquid. The model was used to predict the growth kinetics of an α-Ni/Ni3Sn eutectic dendrite with and without an incident flow in the growth direction. The modelling showed that free eutectic growth is not sensitive to the tip selection parameter of the eutectic dendrite, but is sensitive to incident flow of magnitude larger than eutectic growth velocities. While the larger incident flow increases the eutectic growth velocities generally, it has opposing effects on the interlamellar spacings depending on undercooling. The prediction of the model awaits experimental validation.This article is part of the theme issue \'From atomistic interfaces to dendritic patterns\'.