Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice.

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.

Long-term growth patterns in children born with cleft lip and/or palate. A systematic review.

INTRODUCTION: Introduction: in children with cleft lip and/or palate nutritional status and growth may be impaired due to early life feeding difficulties. Objective: to review the existing literature on the nutritional prognosis during childhood of patients undergoing surgery for cleft lip and/or palate (CLP), their body composition and growth patterns from 2 to 10 years of age, and the possible effects of their early nutritional status on the long-term onset of overweight. Methods: a systematic search of growth and body composition parameters in 2-10 year-old CLP children, including cross-sectional and longitudinal studies, and using the Pubmed and Scopus databases. From the 2,983 retrieved articles, 6 were finally included. Results: two studies out of 6 were longitudinal and the other 4 were cross-sectional, including very heterogeneous samples. Weight and height were used as growth parameters in 2 studies; 2 studies used body mass index (BMI); and the remaining 2 used indexes of nutritional status derived from anthropometric measures. The studies showed discrepancies among results: 3 of them found growth differences between children with CLP and their counterparts, whereas the other 3 did not. The two longitudinal studies did not show any significant differences between the mean BMI z-scores or growth curves of cleft patients and their counterparts. When differences existed, the most affected group was that under 5 years, syndromic children, and adopted children with CL/P. Conclusions: the literature is scarce comparing growth patterns between children with CLP and controls, and results cannot confirm that children with CLP aged 2-10 years, excluding those with syndromes or belonging to vulnerable populations, have different growth patterns or a worse nutritional status than their counterparts.

INTRODUCCIÓN: Introducción: en niños con fisura labial y/o palatina, el estado nutricional y el crecimiento pueden verse afectados debido a dificultades en la alimentación. Objetivos: revisar el pronóstico nutricional de pacientes sometidos a cirugía de fisura labiopalatina (FLP), su composición corporal y sus patrones de crecimiento de los 2 a los 10 años, así como los posibles efectos del estado nutricional durante la primera infancia sobre la aparición posterior de sobrepeso. Métodos: búsqueda sistemática de parámetros de crecimiento y composición corporal en niños con CLP de 2 a 10 años, incluyendo estudios transversales y longitudinales en las bases de datos Pubmed y Scopus. De los 2983 artículos potencialmente relevantes, 6 fueron finalmente incluidos. Resultados: dos estudios de 6 fueron longitudinales y los otros 4, transversales, con muestras muy heterogéneas. El peso y la altura se utilizaron como parámetros de crecimiento en 2 estudios; 2 estudios utilizaron el índice de masa corporal (IMC), y los otros 2, índices del estado nutricional a partir de medidas antropométricas. Los estudios mostraron discrepancias entre los resultados: 3 de ellos encontraron diferencias de crecimiento entre los niños con CLP y sus coetáneos, mientras que los otros 3, no las encontraron. Los dos estudios longitudinales no mostraron diferencias significativas entre el IMC (z-score) ni entre las curvas de crecimiento de los pacientes con FLP y sus coetáneos. Cuando existían diferencias, el grupo más afectado fue el de los menores de 5 años, niños sindrómicos y niños adoptados con CL/P. Conclusiones: la literatura sobre los patrones de crecimiento de los niños con CLP es escasa y los resultados no pueden confirmar que los niños con CLP de 2 a 10 años, excluyendo aquellos con síndromes o pertenecientes a poblaciones vulnerables, tengan patrones de crecimiento diferentes o un peor estado nutricional que sus coetáneos.

Protective effects of Bacillus subtilis ASAG 216 on growth performance, antioxidant capacity, gut microbiota and tissues residues of weaned piglets fed deoxynivalenol contaminated diets.

Deoxynivalenol (DON) poses a serious health threat to animals and humans consuming DON-contaminated food and feed. Biological means of detoxification of DON are considered as one of the effective strategies. The aim of the work was to study ameliorative effects of Bacillus subtilis ASAG 216 on DON-induced toxicosis in piglets. A decrease in average daily gain and average daily feed intake was observed in piglets fed DON-contaminated feed. In addition, DON exposure increased the serum concentrations of aspartate aminotransferase, immunoglobulin A, diamine oxidase, endotoxin, and peptide YY. Moreover, DON exposure caused oxidative stress in the serum, liver and jejunum, induced intestinal inflammation, impaired the intestinal barrier, and disturbed the gut microbiota homeostasis. Supplementation of B. subtilis ASAG 216 effectively attenuated the aforementioned effects of DON on piglets. Moreover, DON and de-epoxy-DON (DOM-1) in the serum, liver and kidney were significantly decreased when B. subtilis ASAG 216 was added to DON-contaminated diet. Our results imply that B. subtilis ASAG 216 can protect against DON-induced toxicosis in piglets, and thus this strain has a potential to be used as an animal feed ingredient to counteract harmful effects of DON in animals.

Association between adenotonsillar hypertrophy and leptin, ghrelin and IGF-1 levels in children.

OBJECTIVE: Developmental and growth retardation is a condition that is often encountered among children with adenotonsillar hypertrophy (ATH). Leptin, ghrelin and IGF-1 are important factors in growth and development for children. The aim of the study was to investigate serum leptin, ghrelin and IGF-1 levels in children with ATH compare with healthy controls. MATERIAL METHOD: 82 children between ages 6-12 were included in this study, divided into two groups. The first group being the study-group consisted of 42 children with obstructive adenotonsillar hypertrophy and the second group being the control-group consisted of 40 healthy children. At 08:30 a.m., peripheral blood samples were extracted from children from both groups to examine the serum levels, and kept in -40 °C until the Elisa test. RESULTS: Leptin serum level of the control-group was found to be statistically significantly higher than the serum leptin level of the ATH group (p = 0,049; p < 0.05). Body mass indexes of the children with ATH were found to be statistically significantly lower than the body mass index (BMI) of the control group (p = 0,001; p < 0.05). In contrast, there was no statistically significant difference between ghrelin and IGF-1 levels between the ATH and control group (p = 0.193, p > 0.05 and p = 0.478, p > 0.05, respectively). CONCLUSION: Upper airway infections are common in children with ATH. Increased airway infections and obstructive enlarged adenotonsillar lymphoid tissue which are caused swallowing difficulties can lead to reduced oral intake and fat tissue. It has led us to think that, ghrelin levels may be increasing secondary to these problems in children with ATH. Furthermore, BMI and leptin would be lower in children with ATH, considering adipose tissue was lesser and leptin was being synthesized and oscillated out of the fat cells of the tissue in these children.

Effects of trichostatin A on FHIT and WWOX genes expression, cell growth inhibition and apoptosis induction in hepatocellular carcinoma WCH 17 cell line

Previously, we evaluated the effect of trichostatin A (TSA) on the expression of DNA methyltransferase 1 (DNMT1) in Hepatocellular Carcinoma (HCC). Fragile histidine triad (FHIT) and WW domain-containing oxidoreductase (WWOX) are two of the most common down-regulated genes in many cancers located on chromosome 3p14.2 and 16q23.3-24.1 respectively. The aim of the current study was to assess the effect of TSA on these genes expression, cell growth, and apoptosis in HCC WCH 17 cell. The cells were seeded and treated with TSA at different times. Then, MTT assay, flow cytometry, and qRT-PCR were achieved to determine viability, apoptosis and gene expression respectively. Cell growth was significantly inhibited, 92 to 36% after 24 h, 86 to 28% after 48 h, and 78 to 24% after 72 h. The results of flow cytometry confirmed that TSA increased apoptosis compared to the control group, the apoptosis percentage increased to 12%, 16%, and 18% in comparison to control groups (2%). Significant up-regulation of the genes was observed in all treated groups. We concluded that re-expression of silenced WWOX and FHIT genes could be achieved by TSA resulting in cell growth inhibition and apoptosis induction in WCH 17 cell.

ERα Signaling in GHRH/Kiss1 Dual-Phenotype Neurons Plays Sex-Specific Roles in Growth and Puberty.

Gonadal steroids modulate growth hormone (GH) secretion and the pubertal growth spurt via undefined central pathways. GH-releasing hormone (GHRH) neurons express estrogen receptor α (ERα) and androgen receptor (AR), suggesting changing levels of gonadal steroids during puberty directly modulate the somatotropic axis. We generated mice with deletion of ERα in GHRH cells (GHRHΔERα), which displayed reduced body length in both sexes. Timing of puberty onset was similar in both groups, but puberty completion was delayed in GHRHΔERα females. Lack of AR in GHRH cells (GHRHΔAR mice) induced no changes in body length, but puberty completion was also delayed in females. Using a mouse model with two reporter genes, we observed that, while GHRHtdTom neurons minimally colocalize with Kiss1hrGFP in prepubertal mice, ∼30% of GHRH neurons coexpressed both reporter genes in adult females, but not in males. Developmental analysis of Ghrh and Kiss1 expression suggested that a subpopulation of ERα neurons in the arcuate nucleus of female mice undergoes a shift in phenotype, from GHRH to Kiss1, during pubertal transition. Our findings demonstrate that direct actions of gonadal steroids in GHRH neurons modulate growth and puberty and indicate that GHRH/Kiss1 dual-phenotype neurons play a sex-specific role in the crosstalk between the somatotropic and gonadotropic axes during pubertal transition.SIGNIFICANCE STATEMENT Late maturing adolescents usually show delayed growth and bone age. At puberty, gonadal steroids have stimulatory effects on the activation of growth and reproductive axes, but the existence of gonadal steroid-sensitive neuronal crosstalk remains undefined. Moreover, the neural basis for the sex differences observed in the clinical arena is unknown. Lack of ERα in GHRH neurons disrupts growth in both sexes and causes pubertal delay in females. Deletion of androgen receptor in GHRH neurons only delayed female puberty. In adult females, not males, a subset of GHRH neurons shift phenotype to start producing Kiss1. Thus, direct estrogen action in GHRH/Kiss1 dual-phenotype neurons modulates growth and puberty and may orchestrate the sex differences in endocrine function observed during pubertal transition.

Subpopulation of Macrophage-Like Plasmatocytes Attenuates Systemic Growth via JAK/STAT in the Drosophila Fat Body.

Drosophila hemocytes, like those of mammals, are given rise from two distinctive phases during both the embryonic and larval hematopoiesis. Embryonically derived hemocytes, mostly composed of macrophage-like plasmatocytes, are largely identified by genetic markers. However, the cellular diversity and distinct functions of possible subpopulations within plasmatocytes have not been explored in Drosophila larvae. Here, we show that larval plasmatocytes exhibit differential expressions of Hemolectin (Hml) and Peroxidasin (Pxn) during development. Moreover, removal of plasmatocytes by overexpressing pro-apoptotic genes, hid and reaper in Hml-positive plasmatocytes, feeding high sucrose diet, or wasp infestation results in increased circulating hemocytes that are Hml-negative. Interestingly these Hml-negative plasmatocytes retain Pxn expression, and animals expressing Hml-negative and Pxn-positive subtype largely attenuate growth and abrogate metabolism. Furthermore, elevated levels of a cytokine, unpaired 3, are detected when Hml-positive hemocytes are ablated, which in turn activates JAK/STAT activity in several tissues including the fat body. Finally, we observed that insulin signaling is inhibited in this background, which can be recovered by concurrent loss of upd3. Overall, this study highlights heterogeneity in Drosophila plasmatocytes and a functional plasticity of each subtype, which reaffirms extension of their role beyond immunity into metabolic regulation for cooperatively maintaining internal homeostatic balance.

Linear growth failure induced by systemic inflammation inhibiting IGF-1/IGFBP axis in rats with asymptomatic colitis.

BACKGROUND: Children in poor areas show significant growth retardation that does not improve with an adequate supply of energy and nutrients, which may be related to asymptomatic intestinal infection caused by poor sanitation. Our objective was to explore the mechanism of intestinal inflammation inhibiting growth in the setting of asymptomatic colitis. METHODS: Forty-eight 3-week-old Wistar rats were randomly divided into three groups: the control group, colitis group (with asymptomatic colitis induced by 2.5% trinitrobenzenesulphonic acid) and pair-fed group (daily food intake matched to the pair in the colitis group). The linear growth was assessed, and the plasma levels of hormone and systemic cytokines were detected and compared by independent two-sample t-test or one-way ANOVA among groups. RESULTS: At d5, the increases in the body length of the control, colitis and pair-fed groups were 1.65 ± 0.34 cm, 1.10 ± 0.30 cm and 1.38 ± 0.26 cm, respectively, and the increase in the body length in the colitis group was significantly less than that in the control group (P < 0.05). There were significant differences in the levels of hormone and cytokines among three groups (P < 0.05). Compared with the control group, rats in the colitis group exhibited linear growth failure, as well as higher expression of calprotectin, tumour necrosis factor-α, interleukin-6 and insulin-like growth factor binding protein 2, lower insulin-like growth factor-1 and insulin-like growth factor binding protein 3, and lower expression of nuclear factor kappa B in hepatocytes. CONCLUSIONS: In addition to undernutrition, the systemic inflammatory response caused by asymptomatic colitis may inhibit the linear growth of rats by its influence on the insulin-like growth factor/insulin-like growth factor binding protein axis.

Effect on Facial Growth of the Management of Cleft Lip and Palate.

Treatment of cleft lip and palate ordinarily requires multiple interventions spanning the time of birth to adulthood. Restriction of facial growth, a common occurrence in affected children, is due to multiple factors. There are multiple surgical and therapeutic options, which may have influence on facial growth in these patients. As restriction to facial development can have significant implications to form, function, and psychological well-being, practitioners should have an appreciation for the effects of the different cleft therapies to facial growth. We have outlined and thoroughly reviewed in chronological order all of the interventions from birth to adulthood necessary in the comprehensive care of the patient with cleft lip and palate, along with the effects they may or may not have on facial growth.

Long-term Growth in Congenital Adrenal Hyperplasia.

OBJECTIVES: To retrospectively assess growth of children with congenital adrenal hyperplasia (CAH) with special reference to puberty and to assess longitudinal growth and final height of subset of children with CAH. METHODS: A retrospective analysis of 30 children (14 boys) with classic CAH (11 salt wasters, 19 simple virilisers) followed up for a mean duration of 9.9 ± 2.4 y (Study period December 2002 through December 2016) was performed. Height Z scores, target height Z scores, height velocities and laboratory parameters were analysed. RESULTS: Children were treated with hydrocortisone in a mean dose of 15.7 ± 3.3 mg/m2/d. Mean 17-hydroxy progesterone in boys and girls were 10.8 ± 6.7 ng/ml and 11.3 ± 9.3 ng/ml respectively. Fifteen children (7 boys) developed central precocious puberty at mean age of 7.6 ± 1.8 y and 13 were treated with GnRH analogues for 3.5 y. Of all patients, 18 (10 girls, 8 boys) reached final height at a mean age of 14.2 ± 1.6 y. Mean final height achieved was 158.0 ± 8.5 cm in boys [target height (TH) -165.5 ± 3.8 cm] and in girls it was 149.9 ± 6.7 cm [target height (TH) 154.7 ± 6.4 cm]. Final height standard deviation scores (SDS) for boys and girls were - 2.06 ± 1.1 (TH-SDS -1.06 ± 0.5) and - 1.47 ± 1.1 (TH-SDS -0.56 ± 1.2) respectively and were not significantly different from target height Z scores (p > 0.05). Growth velocity was attenuated during pubertal years. CONCLUSIONS: Monitoring growth and puberty in children with CAH is critical for optimizing final height.

Distribution-free estimation of local growth rates around interval censored anchoring events.

Biological processes are usually defined on timelines that are anchored by specific events. For example, cancer growth is typically measured by the change in tumor size from the time of oncogenesis. In the absence of such anchoring events, longitudinal assessments of the outcome lose their temporal reference. In this paper, we considered the estimation of local change rates in the outcomes when the anchoring events are interval-censored. Viewing the subject-specific anchoring event times as random variables from an unspecified distribution, we proposed a distribution-free estimation method for the local growth rates around the unobserved anchoring events. We expressed the rate parameters as stochastic functionals of the anchoring time distribution and showed that under mild regularity conditions, consistent and asymptotically normal estimates of the rate parameters could be achieved, with a n convergence rate. We conducted a carefully designed simulation study to evaluate the finite sample performance of the method. To motivate and illustrate the use of the proposed method, we estimated the skeletal growth rates of male and female adolescents, before and after the unobserved pubertal growth spurt (PGS) times.

Influencia de la lactancia materna en los diastemas fisiológicos de crecimiento / Influence of maternal breastfeeding in the physiologic diastema of growth

RESUMEN Introducción: el amamantamiento ha sido la primera forma de alimentación del género humano. Es indiscutible la repercusión de este acto en el desarrollo integral del niño, y el aparato estomatognático no está ajeno a este influjo. Objetivo: identificar el período de lactancia materna y su repercusión en la presencia de los diastemas fisiológicos de crecimiento. Materiales y métodos: se realizó un estudio descriptivo y transversal, se examinaron los 156 niños, de 2 a 5 años de edad, pertenecientes al círculo infantil "Días de Infancia", del área de salud Playa, en el período febrero 2007-febrero 2008. Los datos obtenidos del examen clínico se reflejaron en un formulario confeccionado al efecto. Variables: período de lactancia materna, espacios fisiológicos de crecimiento, espacios de primate. Los datos fueron procesados en tablas y gráficos. Se emplearon análisis estadísticos. Resultados: el 56,4 % de los niños recibieron lactancia por un período menor de 6 meses. El 15.9 % de los que fueron amamantados por un período menor de 6 meses no presentaban estos espacios. Cuando aumentó el periodo de amamantamiento por más de seis meses, la ausencia de espacios disminuyó y solo se evidenció en el 9.0 % de ellos. El 60.6 % reveló la presencia de todos los espacios. El 1.3 % de los niños no recibieron lactancia materna y, sin embargo, si presentaron todos los diastemas fisiológicos de crecimiento. Conclusiones: se determinó que la mayoría de los niños fueron amamantados por un período de 6 meses o menos. Los diastemas fisiológicos de crecimiento estuvieron más representados cuando la lactancia se prolongó por más de 6 meses (AU).

ABSTRACT Introduction: breastfeeding has been the first feeding form of the humankind. The repercussion of this act is undeniable in the comprehensive development of the child, and the stomatognathic system does not escape to this influence. Objective: to identify the period of maternal breastfeeding and its repercussion on the physiologic diastema of growth. Materials and methods: a cross-sectional, descriptive study was carried out in 156 children aged 2-5 years, assisting the day care center "Dias de Infancia", health area Playa, in the period February 2007-February 2008. Data obtained in the clinical examination were shown in a form elaborated for that. The studied variables were maternal breastfeeding period, physiological spaces of growth, primate spaces. Data were processed in tables and graphics. Statistical analyses were used. Results: 56.4 % of the children were breastfed for less than six months. 15.9 % of those who were breastfed for less than six month did not present these spaces. When the breastfeeding period increased for more than six months, the absence of spaces decreased and was evidenced in only 9.0 % of them. 60.6 % showed the presence of all the spaces. 1.3 % of the children were not breastfed, and nevertheless they did show all the physiological diastemata of growth. Conclusions: it was found that most of the children were breastfed for a period of six months or less. Physiological diastemata of growth were more represented when breastfeeding lasted more than six months (AU).

Growth achieved and correlation with blood pressure levels in schoolchildren

SUMMARY INTRODUCTION: The prevalence of systemic arterial hypertension in childhood has increased progressively OBJECTIVE: To analyze blood pressure and height reached by children in public schools in the South of Brazil. METHODS: This is a sectional study of a randomized sample of 1,082 students of six to seven and nine to ten years old used to evaluate blood pressure and height. Blood pressure levels were classified by percentile for gender, age and stature according to the North American reference of National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. RESULTS: Schoolchildren presented adequate growth, which was, on average, higher than the WHO reference values. Blood pressure levels were altered in 13.8% of children, with a higher frequency in the nine and ten year olds (17.6%). The isolated analysis of systolic and diastolic Blood pressure revealed a similar trend, with blood pressure levels higher than the greater the value of the Z-score for stature. CONCLUSION: The schoolchildren in the study evidenced adequate growth and an elevated prevalence of pre-hypertension and arterial hypertension, which tended to be higher in older children and/or those that achieved a greater stature growth.

RESUMO INTRODUÇÃO: A prevalência de hipertensão arterial sistémica na infância aumentou progressivamente. OBJETIVO: Analisar a pressão arterial e a altura alcançada pelas crianças nas escolas públicas do sul do Brasil. MÉTODOS: Estudo transversal de uma amostra aleatória de 1.082 alunos de 6 a 7 e de 9 a 10 anos de idade, para avaliar a pressão arterial e a altura. Os níveis de pressão arterial foram classificados por percentil segundo gênero, idade e estatura, de acordo com a referência norte-americana do Grupo de Trabalho do Programa Nacional de Estudo em Pressão Arterial sobre a pressão arterial elevada em crianças e adolescentes. RESULTADOS: Escolares apresentaram crescimento adequado, que foi, em média, superior aos valores de referência da OMS. Os níveis de pressão arterial foram alterados em 13,8% das crianças, com maior frequência aos 9 e 10 anos de idade (17,6%). A análise isolada da pressão arterial sistólica e diastólica revelou uma tendência similar, com níveis de pressão arterial elevados nas crianças com maiores valores de escore Z para a estatura. CONCLUSÃO: Os escolares no estudo apresentaram um crescimento adequado e uma prevalência elevada de pré-hipertensão e hipertensão arterial, que tendem a ser maiores em crianças mais velhas e/ou naquelas que alcançaram maior crescimento de estatura.

Beyond regulation of pol III: Role of MAF1 in growth, metabolism, aging and cancer.

MAF1 was discovered as a master repressor of Pol III-dependent transcription in response to diverse extracellular signals, including growth factor, nutrient and stress. It is regulated through posttranslational mechanisms such as phosphorylation. A prominent upstream regulator of MAF1 is the mechanistic target of rapamycin (mTOR) pathway. mTOR kinase directly phosphorylates MAF1, controlling its localization and transcriptional activity. In mammals, MAF1 has also been shown to regulate Pol I- and Pol II-dependent transcription. Interestingly, MAF1 modulates Pol II activity both as a repressor and activator, depending on specific target genes, to impact on cellular growth and metabolism. While MAF1 represses genes such as TATA-binding protein (TBP) and fatty acid synthase (FASN), it activates the expression of PTEN, a major tumor suppressor and an inhibitor of the mTOR signaling. Increasing evidence indicates that MAF1 plays an important role in different aspects of normal physiology, lifespan and oncogenesis. Here we will review the current knowledge on MAF1 in growth, metabolism, aging and cancer. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.

Serum n-6 and n-9 Fatty Acids Correlate With Serum IGF-1 and Growth Up to 4 Months of Age in Healthy Infants.

OBJECTIVE: The aim of this study was to study the relationship between insulin-like growth factor-1 (IGF-1), serum phospholipid fatty acids, and growth in healthy full-term newborns during infancy. METHODS: Prospective observational study of a population-based Swedish cohort comprising 126 healthy, term infants investigating cord blood and serum at 2 days and 4 months of age for IGF-1 and phospholipid fatty acid profile and breast milk for fatty acids at 2 days and 4 months, compared with anthropometric measurements (standard deviation scores). RESULTS: At all time-points arachidonic acid (AA) was negatively associated with IGF-1. IGF-1 had positive associations with linoleic acid (LA) at 2 days and 4 months and mead acid (MA) showed positive associations in cord blood. Multiple regression analyses adjusted for maternal factors (body mass index, weight gain, smoking, education), sex, birth weight and feeding modality confirmed a negative association for the ratio AA/LA to IGF-1. MA in cord blood correlated to birth size. Changes in the ratios of n-6/n-3 and AA/docosahexaenoic acid from day 2 to 4 months together with infants' weight and feeding modality determined 55% of the variability of delta-IGF-1. Breast-fed infants at 4 months had lower IGF-1 correlating with lower LA and higher AA concentrations, which in girls correlated with lower weight gain from birth to 4 months of age. CONCLUSIONS: Our data showed interaction of n-6 fatty acids with IGF-1 during the first 4 months of life, and an association between MA and birth size when adjusted for confounding factors. Further follow-up may indicate whether these correlations are associated with later body composition.

Clinical implications of bone marrow adiposity.

Marrow adipocytes, collectively termed marrow adipose tissue (MAT), reside in the bone marrow in close contact to bone cells and haematopoietic cells. Marrow adipocytes arise from the mesenchymal stem cell and share their origin with the osteoblast. Shifts in the lineage allocation of the mesenchymal stromal cell could potentially explain the association between increased MAT and increased fracture risk in diseases such as postmenopausal osteoporosis, anorexia nervosa and diabetes. Functionally, marrow adipocytes secrete adipokines, such as adiponectin, and cytokines, such as RANK ligand and stem cell factor. These mediators can influence both bone remodelling and haematopoiesis by promoting bone resorption and haematopoietic recovery following chemotherapy. In addition, marrow adipocytes can secrete free fatty acids, acting as a energy supply for bone and haematopoietic cells. However, this induced lipolysis is also used by neoplastic cells to promote survival and proliferation. Therefore, MAT could represent a new therapeutic target for multiple diseases from osteoporosis to leukaemia, although the exact characteristics and role of the marrow adipocyte in health and diseases remain to be determined.

Ghrelin and Growth.

Ghrelin is a pleiotropic hormone, whose effect on growth hormone secretion, through the growth hormone secretagogue (GHS) receptor, is one of its many actions. Relationships between GHS receptor gene variants and human height, both in healthy individuals and in patients with growth disorders have been identified. These include constitutional delay in growth and puberty, idiopathic short stature, and isolated growth hormone deficiency. In this review, we provide an overview of the role of ghrelin in growth.

El fallo de medro desde una perspectiva ambulatoria integradora / The failure to thrive from an integrative perspective outpatient

RESUMEN Introducción: el fallo de medro es identificado cuando un niño presenta un crecimiento significativamente menor que sus semejantes, y está asociado frecuentemente con pobre desarrollo mental y psicoemocional. Objetivo: analizar y sintetizar, a través de la producción científica, las características del fallo de medro de un modo integrador, que facilite su abordaje desde la atención ambulatoria. Métodos: se realizó una revisión integrativa, conducida de acuerdo con las siguientes etapas: identificación del tema y elaboración de la pregunta de investigación, establecimiento de los criterios de inclusión y exclusión, definición de las informaciones que serían extraídas de los estudios seleccionados, selección de banco y bases de datos para consulta, evaluación de los estudios incluidos en la revisión, interpretación de los resultados y presentación de la síntesis del conocimiento. Conclusiones: el fallo de medro tiene una etiología multifactorial, siendo su prevalencia variable. Se han identificado factores de riesgo biológicos, socioculturales y ambientales. Existe discrepancia entre los autores sobre los elementos diagnósticos para su identificación, constituyendo los criterios estáticos y dinámicos los de mayor aceptación. La clave del éxito radica en la prevención(AU)

ABSTRACT Introduction: Failure to thrive is identified when a child has a significantly lower growth than its peers and is often associated with poor mental and psycho-emotional development. Objective: Analyze and synthesize, through scientific production, the characteristics of failure to thrive in an integrated way that facilitates its approach from outpatient care. Methods: an integrative review, conducted in accordance with the following steps are performed: identification of the subject and development of the research question, establishing the criteria for inclusion and exclusion definition of the information that would be extracted from the selected studies, selection of bank and databases for consultation, evaluation studies included in the review, interpretation of results and presentation of the synthesis of knowledge. Conclusions: The failure to thrive has a multifactorial etiology, with its variable prevalence. Factors have been identified biological, sociocultural and environmental risk. There is a discrepancy between the authors on diagnostic elements for identification, constituting the static and dynamic criteria the most widely accepted. The key to success lies in prevention(AU)

Five-Year Follow-Up of Midface Distraction in Growing Children with Syndromic Craniosynostosis.

BACKGROUND: Maxillary position in patients with syndromic craniosynostosis after midface distraction has been shown to be stable 1 year postoperatively. The purpose of this study is to assess midfacial position in the growing child with craniosynostosis 5 years after Le Fort III advancement with a rigid external device. METHODS: Seventeen consecutive patients were identified to have the diagnosis of syndromic craniosynostosis and had undergone midface advancement [corrected]. There were 10 boys and seven girls, seven patients had Crouzon syndrome, five had Apert syndrome, and five had Pfeiffer syndrome. A standard subcranial Le Fort III osteotomy was performed. Cephalometric analysis was performed to assess the position of the maxilla. RESULTS: After device removal, orbitale advanced 13.67 mm along the x axis and downward 1.70 mm along the y axis. The A point advanced 15.97 mm along the x axis and downward 1.14 mm along the y axis. At 1 year after distraction, both orbitale and A point had advanced an additional 0.47 mm and 0.24 mm along the x axis and downward 0.58 mm and 1.78 mm along the y axis, respectively. At 5 years after distraction, the orbitale moved posterior 0.58 mm and the A point advanced an additional 2.08 mm along the x axis. Orbitale and A point descended 3.23 mm and 5.2 mm along the y axis, respectively. CONCLUSION: After Le Fort III advancement with distraction, the maxillary position remains stable and continues to advance minimally along the x axis and demonstrates more growth along the y axis over the long term. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Effects of Diagnosis by Newborn Screening for Cystic Fibrosis on Weight and Length in the First Year of Life.

Importance: Since the implementation of universal newborn screening (NBS) for cystic fibrosis (CF), the timing and magnitude of growth deficiency or its association with correlates of disease among infants with CF who underwent NBS has not been well described. Objective: To examine incremental weight gain, linear growth, and clinical features in the first year of life among infants with CF who underwent NBS. Design, Setting, and Participants: The Baby Observational and Nutrition Study (BONUS), a multicenter, longitudinal, observational cohort study, was conducted during regular CF clinic visits in the first 12 months of life at 28 US Cystic Fibrosis Foundation-accredited Care Centers from January 7, 2012, through May 31, 2015. Participants included 231 infants younger than 3.5 months who underwent NBS and had confirmed CF, with a gestational age of at least 35 weeks, birth weight of at least 2.5 kg, and toleration of full oral feeds. Of these, 222 infants (96.1%) had follow-up beyond 6 months of age and 215 (93.1%) completed 12 months of follow-up. Exposure: Cystic fibrosis. Main Outcome and Measures: Attained weight and length for age and World Health Organization normative z scores at ages 1 to 6 and 8, 10, and 12 months (defined a priori). Results: Of the 231 infants enrolled, 110 infants (47.6%) were female and 121 (52.4%) were male, with a mean (SD) age of 2.58 (0.69) months. BONUS infants had lower than mean birth weights (mean z score, -0.15; 95% CI, -0.27 to -0.04) and higher birth lengths (mean z score, 0.44; 95% CI, 0.26 to 0.62). They achieved normal weight by 12 months, a significant improvement over a prescreening cohort of newborns with CF from 20 years before the contemporary cohort (mean z score increase, 0.57; 95% CI, 0.37-0.77). However, length was lower than the mean at 12 months (mean z score, -0.56; 95% CI, -0.70 to -0.42). Only 30 infants (13.6%) were at less than the 10th percentile of weight for age, whereas 53 (23.9%) were at less than the 10th percentile of length for age at more than half their visits. Male sex, pancreatic insufficiency, meconium ileus, histamine blocker use, and respiratory Pseudomonas aeruginosa infection were associated with lower weight or length during the first year. Insulinlike growth factor 1 levels were significantly lower among low-length infants. Persistently low-weight infants consumed significantly more calories, and weight and length z scores were negatively correlated with caloric intake. Conclusions and Relevance: Since initiation of universal NBS for CF, significant improvement has occurred in nutritional status, with normalization of weight in the first year of life. However, length stunting remains common.