PRIM1 deficiency causes a distinctive primordial dwarfism syndrome.

DNA replication is fundamental for cell proliferation in all organisms. Nonetheless, components of the replisome have been implicated in human disease, and here we report PRIM1 encoding the catalytic subunit of DNA primase as a novel disease gene. Using a variant classification agnostic approach, biallelic mutations in PRIM1 were identified in five individuals. PRIM1 protein levels were markedly reduced in patient cells, accompanied by replication fork asymmetry, increased interorigin distances, replication stress, and prolonged S-phase duration. Consequently, cell proliferation was markedly impaired, explaining the patients' extreme growth failure. Notably, phenotypic features distinct from those previously reported with DNA polymerase genes were evident, highlighting differing developmental requirements for this core replisome component that warrant future investigation.

Weight Velocity in Addition to Latest Weight Does Not Improve the Identification of Wasting or the Prediction of Stunting and Mortality: A Longitudinal Analysis Using Data from Malawi, South Africa, and Pakistan.

BACKGROUND: In low/middle-income countries, most nutritional assessments use the latest weights, without reference to growth trajectory. OBJECTIVES: This study explores whether velocity, in addition to the latest weight, improves the prediction of wasting, stunting, or mortality in the first 2 years of life. METHODS: We analyzed a combined data set with weight and height data collected monthly in the first year of 3447 children from Pakistan, Malawi, and South Africa, with height and survival recorded till 24 m. The main exposures were weight-for-age z-score (WAZ) at the end of each 2-m period and weight velocity-for-age z-score (WVZ2) across that period. The outcomes were wasting, stunting, or all-cause mortality in the next 1-2 mo. As a sensitivity analysis, we also used WVZ over 6 mo (WVZ6), with matching WAZ. Cox proportional hazard models with repeated growth measures were used to study the association between exposures and mortality. Mixed Poisson models were used for stunting and wasting. RESULTS: Children who were already stunted or wasted were most likely to remain so. Higher WVZ2 was associated with a lower risk of subsequent stunting (risk ratio [RR]: 0.95; 95% confidence interval [CI]: 0.93, 0.96), but added minimal prediction (difference in AUC = 0.004) compared with a model including only WAZ. Similarly, lower WVZ2 was associated with wasting (RR: 0.74; 95% CI 0.72, 0.76) but the prediction was only marginally greater than for WAZ (difference in AUC = 0.015). Compared with WAZ, WVZ6 was less predictive for both wasting and stunting. Low WVZ6 (but not WVZ2) was associated with increased mortality (hazard ratios: 0.75, 95% CI: 0.67, 0.85), but added only marginal prediction to a model including WAZ alone (difference in C = 0.015). CONCLUSIONS: The key anthropometric determinant of impending wasting, stunting, and mortality appears to be how far below the normal range the child's weight is, rather than how they reached that position.

Growth development of children and adolescents with inflammatory bowel disease in the period 2000-2014 based on data of the Saxon pediatric IBD registry: a population-based study.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) in children is on the increase worldwide. Growth disorders are common in pediatric patients with inflammatory bowel disease. The aim of this paper is to investigate anthropometric indicators, including height and weight in children with inflammatory bowel disease in Saxony, one of the German federal states, and to evaluate growth trends in patients by comparing their height and weight with that of healthy children in Germany. METHODS: In Saxony, all children and adolescents with IBD were registered in the Saxon Pediatric IBD Registry from 2000 to 2014. The data used are therefore based on a total area-wide survey over 15 years. For this study, 421 datasets of children and adolescents aged 0-14 years with Crohn's disease (CD) (n = 291) or ulcerative colitis (UC) (n = 130) were analyzed. Z-score and percentile calculations were used to compare differences between IBD patients and the general population. RESULTS: The children with CD or UC (both sexes) had a significant lower weight at diagnosis (the mean weight z-score had negative values) versus the general population. The weight values lay mostly below P50 (the 50th percentile, median), more precisely, mostly between P10 and P50 of the body weight child growth curve for corresponding sexes (KiGGS 2003-2006). The height values of both sexes at diagnosis lay also mostly below P50 (the 50th percentile, median) of the child body growth curve for corresponding sexes (KiGGS 2003-2006), i.e. the mean height z-score was negative. But only the children with CD had a significant lower height, more precisely, mostly between P25 and P50 versus the general population (KIGGS). For children with UC the difference was not significant. CONCLUSION: In pediatric patients with IBD the possibility of growth disturbance, mainly in the form of weight retardation, is very probable.

Risk factors associated with underweight in children aged one to two years: a longitudinal study.

BACKGROUND: Underweight is a prevalent health issue in children. This study aimed to identify factors associated with underweight in children aged 1-2 years in Hamadan city. Unlike the studies conducted in this field, which are cross-sectional and do not provide information on the effect of age changes on underweight, our longitudinal approach provides insights into weight changes over time. On the other hand, this study focuses on the high-risk age group of 1 to 2 years, which has only been addressed in a few studies. METHODS: In this longitudinal study, 414 mothers with 1 to 2 year-old children referred to the health centers of Hamadan city, whose information is in the SIB system, a comprehensive electronic system, were examined to identify factors related to underweight. The response variable was weight-for-age criteria classified into three categories: underweight, normal weight, and overweight. A two-level longitudinal ordinal model was used to determine the factors associated with underweight. RESULTS: Of the children studied, 201 (48.6%) were girls and 213 (51.4%) were boys. Significant risk factors for underweight included low maternal education (AOR = 3.56, 95% CI: 1.10-11.47), maternal unemployment (AOR = 3.38, 95% CI: 1.05-10.91), maternal height (AOR = 0.85, 95% CI: 0.79-0.92), lack of health insurance (AOR = 2.85, 95% CI: 1.04-7.84), gestational age less than 24 years (AOR = 3.17, 95% CI: 16.28-0.97), child age 12-15 months (AOR = 2.27, 95% CI: 1.37-3.74), and child's birth weight (AOR = 0.63, 95% CI: 0.70-0.58). CONCLUSION: Based on the results of the present study, it seems that the possibility of being underweight among children is more related to the characteristics of mothers; therefore, taking care of mothers can control some of the weight loss of children.

The role of radiography in diagnosing, monitoring and prognosing juvenile idiopathic arthritis.

The current role of conventional radiography in the diagnosis, monitoring and prognosis of juvenile idiopathic arthritis (JIA) is reviewed, as its role has changed with the increasing use of ultrasound and magnetic resonance imaging, as well as with the introduction of biological drugs. Conventional radiography does not play an important role in the diagnosis of JIA, as this is based on history, clinical examination and laboratory findings. The main role of conventional radiography is in the detection and monitoring of growth disorders and chronic structural and morphological changes of the affected joints and bones, in addition to helping with the differential diagnosis of conditions that mimic JIA. Radiographic changes of the joints depend on the age of the child, the type and duration of arthritis and the specific joints affected. There are no standard protocols for arthritis monitoring and most indications for imaging are based on individual case-by-case decisions. The development of degenerative joint changes is considered a poor predictive factor, but there are no clear studies that more precisely define the predictive value of radiographic changes. Conventional radiography remains an important imaging modality in narrowing the differential diagnosis and in evaluating growth disorders and the developing destructive joint changes.

Acceleration of skeletal maturation in Central Europe over the last two decades: insights from two cohorts of healthy children.

BACKGROUND: Deviations between the determination of bone age (BA) according to Greulich and Pyle (G&P) and chronological age (CA) are common in Caucasians. Assessing these discrepancies in a population over time requires analysis of large samples and low intra-observer variability in BA estimation, both can be achieved with artificial intelligence-based software. The latest software-based reference curve contrasting the BA determined by G&P to the CA of Central European children dates back over two decades. OBJECTIVE: To examine whether the reference curve from a historical cohort from the Netherlands (Rotterdam cohort) between BA determined by G&P and CA still applies to a current Central European cohort and derive a current reference curve. MATERIALS AND METHODS: This retrospective single-center study included 1,653 children and adolescents (aged 3-17 years) who had received a radiograph of the hand following trauma. The G&P BA estimated using artificial intelligence-based software was contrasted with the CA, and the deviations were compared with the Rotterdam cohort. RESULTS: Among the participants, the mean absolute error between BA and CA was 0.92 years for girls and 0.97 years for boys. For the ages of 8 years (boys) and 11 years (girls) and upward, the mean deviation was significantly greater in the current cohort than in the Rotterdam cohort. The reference curves of both cohorts also differed significantly from each other (P < 0.001 for both boys and girls). CONCLUSION: The BA of the current Central European population and that of the curve from the Rotterdam cohort from over two decades ago differ. Whether this effect can be attributed to accelerated bone maturation needs further evaluation.

A premarital services education model of preventing stunting among prospective newlyweds from North Sumatera, Indonesia.

Stunting, attributed to insufficient nutrition during the critical first 1000 days of life, remains a pressing public health issue in North Sumatera, Indonesia. This study investigates the influence of pre-marital education on prospective couples' knowledge and nutritional status as a stunting prevention strategy. Employing a quantitative, cross-sectional design, the study involved 1000 prospective couples across 10 districts. Data were collected through structured questionnaires and analyzed using Structural Equation Modeling (SEM). The findings demonstrate that pre-marital education significantly enhances knowledge of nutrition, family planning, and stunting prevention, leading to improved nutritional status. However, increased knowledge of stunting was inversely related to nutritional status. The study concludes that comprehensive pre-marital education is vital for effective stunting prevention. It recommends a thorough revision of pre-marital educational content, emphasizing a tailored and integrative approach to health and nutrition, to address specific regional challenges and enhance overall program efficacy.

Le retard de croissance, attribué à une nutrition insuffisante au cours des 1 000 premiers jours critiques de la vie, reste un problème de santé publique urgent dans le nord de Sumatera, en Indonésie. Cette étude examine l'influence de l'éducation prénuptiale sur les connaissances et l'état nutritionnel des futurs couples en tant que stratégie de prévention du retard de croissance. Utilisant une conception quantitative et transversale, l'étude a porté sur 1 000 couples potentiels dans 10 districts. Les données ont été collectées au moyen de questionnaires structurés et analysées à l'aide de la modélisation d'équations structurelles (SEM). Les résultats démontrent que l'éducation prénuptiale améliore considérablement les connaissances en matière de nutrition, de planification familiale et de prévention du retard de croissance, conduisant ainsi à une amélioration de l'état nutritionnel. Cependant, une meilleure connaissance du retard de croissance était inversement liée à l'état nutritionnel. L'étude conclut qu'une éducation prénuptiale complète est essentielle pour une prévention efficace du retard de croissance. Il recommande une révision approfondie du contenu éducatif prénuptial, en mettant l'accent sur une approche adaptée et intégrative de la santé et de la nutrition, pour relever les défis régionaux spécifiques et améliorer l'efficacité globale du programme.

Fracture risk and impact in boys with Duchenne muscular dystrophy: A retrospective cohort study.

INTRODUCTION/AIMS: Boys with Duchenne muscular dystrophy (DMD) are at increased risk of fracture. This study investigated the incidence of fractures, factors contributing to risk of first fracture with emphasis on body mass index (BMI), and the impact of fractures on functional capacity in an Australian cohort of boys with DMD. METHODS: A retrospective cohort study included boys with DMD who attended a pediatric neuromuscular clinic from 2011 to 2018. Information regarding fractures, anthropometry measurements, body composition and functional assessment was collected. Factors associated with first fracture risk were analyzed with Cox-proportional hazards. Longitudinal analysis of function post-fracture was also conducted. RESULTS: This study included 155 boys with DMD. At least one fracture occurred in 71 (45%) boys; overall incidence of fractures was 399-per-10,000 persons-years. The first fracture was vertebral in 55%; 41% had non-vertebral fractures and 4% had both. Vertebral fractures occurred in significantly older (12.28 vs 9.28 y) boys with longer exposure to glucocorticoids (5.45 vs 2.50 y) compared to non-vertebral fractures. Boys with a history of fracture(s) had a steeper rate of functional decline (measured by Northstar Ambulatory Assessment score) than those with no recorded fractures. DISCUSSION: A high fracture burden was observed in a large Australian cohort of boys with DMD. Further investigation is required to understand preventative strategies and modifiable risk factors to reduce the incidence of fractures in DMD. The impact on fractures on ambulatory capacity should be closely monitored.

Accommodation and disability-specific differences in nutritional status of children with disabilities in Kathmandu, Nepal: A cross-sectional study.

BACKGROUND: Worldwide, more than 150 million children < 18 years live with disabilities. These children are more vulnerable to malnutrition regardless of institutional care that they receive, such as daycare or residential care. In Nepal, little is known about the status of malnutrition and factors associated with malnutrition among children with disabilities. This study was conducted to investigate the factors associated with malnutrition based on the types of disability and accommodation. METHODS: This institution-based, cross-sectional study was conducted in 22 institutions in the Kathmandu Valley, Nepal. From these institutions, parents/guardians of all children with disabilities were recruited who were present there on the day of data collection. They were interviewed using a structured questionnaire. The questionnaire included questions on demographic characteristics, disability type and severity, accommodation place, feeding practices, and dietary patterns. The outcome variables, stunting, underweight, and obesity were measured using height-for-age, weight-for-age, and body mass index-for-age, respectively. A generalized linear model was used to investigate the factors associated with stunting and underweight, and multinomial logistic regression was used to identify the factors associated with overweight and obesity. RESULTS: Among the 345 children with disabilities, 45% were stunted, 33% were underweight, 19% were thin, and 12% were overweight. Children with physical disabilities (relative risk ratio = 1.88, 95% confidence interval [CI] = 1.26-2.81) were more likely to be stunted than those with sensory disabilities. Children with autism (adjusted odds ratio [aOR] = 5.56, 95% CI: 1.23-25.23) and intellectual disabilities (aOR = 5.84, 95% CI: 1.59-21.51) were more likely to be overweight and obese than those with sensory disabilities. No evidence was found regarding an association between accommodation type and malnutrition. CONCLUSION: Children with disabilities are vulnerable to malnutrition in several ways. Different types of disabilities are associated with different forms of malnutrition. Considering the types of disabilities, tailor-made approaches should be adopted to improve malnutrition status.

Patterns in child stunting by age: A cross-sectional study of 94 low- and middle-income countries.

Child stunting prevalence is primarily used as an indicator of impeded physical growth due to undernutrition and infections, which also increases the risk of mortality, morbidity and cognitive problems, particularly when occurring during the 1000 days from conception to age 2 years. This paper estimated the relationship between stunting prevalence and age for children 0-59 months old in 94 low- and middle-income countries. The overall stunting prevalence was 32%. We found higher stunting prevalence among older children until around 28 months of age-presumably from longer exposure times and accumulation of adverse exposures to undernutrition and infections. In most countries, the stunting prevalence was lower for older children after around 28 months-presumably mostly due to further adverse exposures being less detrimental for older children, and catch-up growth. The age for which stunting prevalence was the highest was fairly consistent across countries. Stunting prevalence and gradient of the rise in stunting prevalence by age varied across world regions, countries, living standards and sex. Poorer countries and households had a higher prevalence at all ages and a sharper positive age gradient before age 2. Boys had higher stunting prevalence but had peak stunting prevalence at lower ages than girls. Stunting prevalence was similar for boys and girls after around age 45 months. These results suggest that programmes to prevent undernutrition and infections should focus on younger children to optimise impact in reducing stunting prevalence. Importantly, however, since some catch-up growth may be achieved after age 2, screening around this time can be beneficial.

Knowledge and action related to stimulation development of stunted children.

Objectives: To analyse the correlation of parental knowledge and parental stimulation with toddler stunting. Method: The cross-sectional study was conducted in April 2020 at the Tlanakan Health Centre, Pamekasan Regency, Indonesia, and comprised mothers of stunted children aged 6-36 months who had no comorbid disease. Data was collected using a questionnaire and a checklist. Data was analysed SPSS with Spearmen Rank correlation. RESULTS: Of the 186 mothers, 125(67.2%) were aged 20-30 years, and 168(90.3%) were housewives. Among the children, 97(52.2%) were boys and 89(47.8%) were girls. The largest age group was that of 25-36 months 80(43%). There was a significant correlation of parental knowledge and stimulation with the development of stunting toddlers (p=0.001). CONCLUSIONS: Parental knowledge and actions of developmental stimulation by parents were related to the quality of development of the stunted children.

Altered DNA methylation at age-associated CpG sites in children with growth disorders: impact on age estimation?

Age estimation based on DNA methylation (DNAm) can be applied to children, adolescents and adults, but many CG dinucleotides (CpGs) exhibit different kinetics of age-associated DNAm across these age ranges. Furthermore, it is still unclear how growth disorders impact epigenetic age predictions, and this may be particularly relevant for a forensic application. In this study, we analyzed buccal mucosa samples from 95 healthy children and 104 children with different growth disorders. DNAm was analysed by pyrosequencing for 22 CpGs in the genes PDE4C, ELOVL2, RPA2, EDARADD and DDO. The relationship between DNAm and age in healthy children was tested by Spearman's rank correlation. Differences in DNAm between the groups "healthy children" and the (sub-)groups of children with growth disorders were tested by ANCOVA. Models for age estimation were trained (1) based on the data from 11 CpGs with a close correlation between DNAm and age (R ≥ 0.75) and (2) on five CpGs that also did not present significant differences in DNAm between healthy and diseased children. Statistical analysis revealed significant differences between the healthy group and the group with growth disorders (11 CpGs), the subgroup with a short stature (12 CpGs) and the non-short stature subgroup (three CpGs). The results are in line with the assumption of an epigenetic regulation of height-influencing genes. Age predictors trained on 11 CpGs with high correlations between DNAm and age revealed higher mean absolute errors (MAEs) in the group of growth disorders (mean MAE 2.21 years versus MAE 1.79 in the healthy group) as well as in the short stature (sub-)groups; furthermore, there was a clear tendency for overestimation of ages in all growth disorder groups (mean age deviations: total growth disorder group 1.85 years, short stature group 1.99 years). Age estimates on samples from children with growth disorders were more precise when using a model containing only the five CpGs that did not present significant differences in DNAm between healthy and diseased children (mean age deviations: total growth disorder group 1.45 years, short stature group 1.66 years). The results suggest that CpGs in genes involved in processes relevant for growth and development should be avoided in age prediction models for children since they may be sensitive for alterations in the DNAm pattern in cases of growth disorders.

Effect of educational intervention based on health belief model on mothers monitoring growth of 6-12 months child with growth disorders.

BACKGROUND: Maternal education is one of the main ways to improve children's nutritional behaviors and development. The purpose of this study is to investigate the effect of educational intervention based on Health Belief Model (HBM) on mothers monitoring growth of 6-12 months child with growth disorders in Ghirokarzin city, Fars Provonce, Iran. METHODS: This quasi-experimental study was conducted on mothers of 6-12 months children with growth disorders of Ghirokarzin city, Fars province, Iran in 2021-2022. One hundred twenty mothers of 6-12 months child with growth disorders in Ghirokarzin city were selected using random sampling method and were divided into two groups of intervention (60) and control (60). The experimental group received training on the HBM constructs. Both groups completed the questionnaire before and three months after. INTERVENTION: A questionnaire beased on Health Belief Model constructs were used to collect information. The data was analyzed with SPSS 22 software using paired t-tests, Chi-square tests, and independent t-tests, with a significance level of 0.05. RESULTS: Three months after the educational intervention, the experimental group showed a significant increase in terms of knowledge, HBM constructs, weight of the children and feeding behavior. CONCLUSION: This study showed the educational intervention based on the HBM improved the knowledge and feeding behavior of mothers and improved Growth Disorders of child. Hence, this model can act as a framework for designing and implementing educational interventions for prevention of growth disorders in children.

Adolescent boys with constitutional delay of growth and puberty grow faster than patients with organic growth hormone deficiency.

OBJECTIVE: Constitutional delay of growth and puberty (CDGP) is a tempo variant with a good prognosis. Healthy late-maturing adolescents grow slower than postulated by age-related references, and therefore, CDGP is frequently confused with growth hormone deficiency (GHD). For differential diagnosis, height velocity references for CDGP are needed. DESIGN AND PATIENTS: Here, we provide height velocity data for late-maturing boys based on mixed longitudinal and cross-sectional observations in a group of 38 German adolescents with proven CDGP and compare them with cross-sectional observations in a group of 164 adolescents with organic GHD from the National Cooperative Growth Study registry. RESULTS: In the critical age interval from 13.4 to 14.9 years, the growth of prepubertal adolescents with CDGP was faster (mean/median height velocity, 5.2/5.4 cm/years; quartiles, 4.4-6.2 cm/years) than that of prepubertal adolescents with organic GHD (3.5/3.2 cm/years; quartiles, 2.0-4.4 cm/years) in the cross-sectional analysis (p < .0001). Based on our mixed longitudinal and cross-sectional analysis, the height velocity of adolescent boys with CDGP exceeded previous model calculations on average by 1.0 cm. CONCLUSIONS: In conclusion, prepubertal adolescents with CDGP grow faster than patients with organic GHD. Previous model estimates underestimated height velocity of boys with CDGP.

Skeletal disproportion in girls with Turner syndrome and longitudinal change with growth-promoting therapy.

OBJECTIVE: Short stature in Turner syndrome (TS) may be accompanied by skeletal disproportion. This retrospective study investigates growth and disproportion from early childhood to adult height. STUDY DESIGN: Data were collected from 59 girls prior to growth hormone (rhGH) treatment and in 30 girls followed up longitudinally. Standard deviation scores (SDS) for height (Ht), sitting height (SH) and sub-ischial leg length (LL) were compared and a disproportion score (SH SDS - LL SDS) calculated. RESULTS: In 59 girls, mean (SD) age 6.6 (2.1) years prior to rhGH treatment, LL SDS of -3.4 (1.1) was significantly lower than SH SDS of -1.2 (0.8) [p < .001]. In girls with Ht SDS < -2.0, disproportion score was > +2.0 in 27 (63%), cf eight (50%) with Ht SDS ≥ -2.0. For the longitudinal analysis, skeletal disproportion prior to rhGH was +2.4 (1.1) and +1.7 (1.0) on rhGH but prior to introduction of oestrogen [p < .001]. Disproportion at adult height was +1.1 (0.8), which was less marked than at the earlier time points [p < .001 for both comparisons]. Change in disproportion SDS over the first two years of rhGH predicted overall change in disproportion from baseline to adult height [R2 51.7%, p < .001]. CONCLUSION: TS is associated with skeletal disproportion, which is more severe in the shortest girls and present in only half of those with milder degrees of short stature. Growth-promoting therapy may improve disproportion during both the childhood and pubertal phases of growth. Change in disproportion status two years after starting rhGH helps predict disproportion at adult height.

Successful pregnancies in an adult with Meier-Gorlin syndrome harboring biallelic CDT1 variants.

Meier-Gorlin syndrome is an autosomal recessively inherited disorder of growth retardation, accompanied by microtia and patellae a/hypoplasia and characteristic facies. Pathogenic variants in genes associated with the initiation of DNA replication underlie the condition, with biallelic variants in CDT1 the most common cause. Using 10× Chromium genome sequencing, we report CDT1 variants in an adult female, with an inframe amino acid deletion inherited in trans with a deep intronic variant which likely serves as the branchpoint site in Intron 8. Splicing defects arising from this variant were confirmed through in vitro analysis. At 49 years, she represents the oldest patient with a molecular diagnosis described in the literature and is the first reported patient with Meier-Gorlin syndrome to have carried a successful pregnancy to term. Both of her pregnancies were complicated by postpartum hemorrhage and upon subsequent necessary hysterectomy, revealed uterine abnormalities. There is scant knowledge on reproductive ability and success in patients with Meier-Gorlin syndrome. Successful pregnancies among other clinically recognizable forms of primordial dwarfism have also not been described previously. This case is therefore of clinical interest for many forms of inherited growth retardation, and will assist in providing more information and clinical guidance for females of reproductive age.

Centrosomes: The good and the bad for brain development.

Centrosomes nucleate and organise the microtubule cytoskeleton in animal cells. These membraneless organelles are key structures for tissue organisation, polarity and growth. Centrosome dysfunction, defined as deviation in centrosome numbers and/or structural integrity, has major impact on brain size and functionality, as compared with other tissues of the organism. In this review, we discuss the contribution of centrosomes to brain growth during development. We discuss in particular the impact of centrosome dysfunction in Drosophila and mammalian neural stem cell division and fitness, which ultimately underlie brain growth defects.

Longitudinal growth patterns and final height in childhood-onset systemic lupus erythematosus.

Patients with childhood-onset systemic lupus erythematosus (cSLE) are at risk of becoming short adults. To evaluate the growth patterns and risk factors of short final height, a retrospective study was conducted in 97 patients (87 females, 90%) with cSLE who grew from the time of diagnosis and reached their final height. The primary outcome was the final height. Participants were divided into participants with short final height (final height standard deviation score (HSDS) < - 2, n = 22, 23%) and participants with normal final height (final HSDS ≥ - 2, n = 75, 77%). At diagnosis, the mean age was 11.3 ± 2.4 years and HSDS was - 0.5 ± 1.3. The participants reached the final height of 1.51 ± 0.08 m (final HSDS - 1.3 ± 0.1) at mean age of 16.2 ± 2.3 years. The HSDS of participants with short final height steadily declined throughout the course of SLE (p = 0.02), and were significantly lower than participants with normal final height at any time point (p < 0.001). In participants with normal final height, HSDS significantly declined from baseline until 2 years after diagnosis (p = 0.01), and then became stable thereafter. The independent risk factors for short final height were the male sex, short stature at diagnosis, low body weight at final height, and cumulative corticosteroid dose.Conclusion: A substantial number of the participants with cSLE became short adults. Adequate nutrition and corticosteroid minimization should be emphasized in patients at high risk for short final height. What is known? • Growth failure is common in SLE due to many risk factors including chronic inflammation, malnutrition, and long-term use of corticosteroids. • In comparison to growth failure, final height is a better indicator of growth as the prevalence of growth failure is variable depending on definitions, patient age and pubertal status. What is new? • Nearly one fourth of children with SLE have short final height. • The independent risk factors for short final height were the male sex, short stature at diagnosis, low body weight at final height, and cumulative corticosteroid dose.

Runting and Stunting Syndrome in Broiler Chickens: Histopathology and Association With a Novel Picornavirus.

Runting stunting syndrome (RSS) in commercial chickens has been reported worldwide, and although several studies have attempted to clarify the cause and describe the lesions, there are gaps in knowledge of the epidemiology, pathogenesis, and etiology. The study objective was to use commercial chicks naturally affected by RSS to describe the histologic changes of RSS in all segments of the small intestine in chicks of different ages and to identify viral gene sequences in affected chicks and their association with histologic lesions. Chicks lacking clinical signs but from the same houses and from unaffected houses were used as controls. The average weight of affected chicks was significantly lower than expected for their flocks. Macroscopically, the small intestines had paler serosa, with watery, mucoid, or foamy contents and poorly digested food. Histologic lesions were characterized by necrotic crypts, crypt dilation, and flattening of the crypt epithelium. Histomorphometry of the intestines revealed villous atrophy especially in the jejunum and ileum. Histologic changes in other organs were not observed. Random next-generation sequencing of total RNA extracted from formalin-fixed paraffin-embedded tissues detected avian nephritis virus, avian rotavirus, and picornavirus in jejunal segments from 7-day-old chicks. No viruses were detected in the jejunum of 1-day-old chicks. Detection of picornaviral reads was significantly associated (P < .05) with histologic lesions of RSS. Sequence analysis of the picornavirus revealed genetic similarity with the genus Gallivirus. Using in situ hybridization for galliviral nucleic acid sequences, the signal was associated with crypt lesion severity, although signal was detected both in chicks with and without RSS.

An eHealth Framework for Managing Pediatric Growth Disorders and Growth Hormone Therapy.

BACKGROUND: The use of technology to support health and health care has grown rapidly in the last decade across all ages and medical specialties. Newly developed eHealth tools are being implemented in long-term management of growth failure in children, a low prevalence pediatric endocrine disorder. OBJECTIVE: Our objective was to create a framework that can guide future implementation and research on the use of eHealth tools to support patients with growth disorders who require growth hormone therapy. METHODS: A total of 12 pediatric endocrinologists with experience in eHealth, from a wide geographical distribution, participated in a series of online discussions. We summarized the discussions of 3 workshops, conducted during 2020, on the use of eHealth in the management of growth disorders, which were structured to provide insights on existing challenges, opportunities, and solutions for the implementation of eHealth tools across the patient journey, from referral to the end of pediatric therapy. RESULTS: A total of 815 responses were collected from 2 questionnaire-based activities covering referral and diagnosis of growth disorders, and subsequent growth hormone therapy stages of the patient pathway, relating to physicians, nurses, and patients, parents, or caregivers. We mapped the feedback from those discussions into a framework that we developed as a guide to integration of eHealth tools across the patient journey. Responses focused on improved clinical management, such as growth monitoring and automation of referral for early detection of growth disorders, which could trigger rapid evaluation and diagnosis. Patient support included the use of eHealth for enhanced patient and caregiver communication, better access to educational opportunities, and enhanced medical and psychological support during growth hormone therapy management. Given the potential availability of patient data from connected devices, artificial intelligence can be used to predict adherence and personalize patient support. Providing evidence to demonstrate the value and utility of eHealth tools will ensure that these tools are widely accepted, trusted, and used in clinical practice, but implementation issues (eg, adaptation to specific clinical settings) must be addressed. CONCLUSIONS: The use of eHealth in growth hormone therapy has major potential to improve the management of growth disorders along the patient journey. Combining objective clinical information and patient adherence data is vital in supporting decision-making and the development of new eHealth tools. Involvement of clinicians and patients in the process of integrating such technologies into clinical practice is essential for implementation and developing evidence that eHealth tools can provide value across the patient pathway.