ABSTRACT
Purpose: Exosomes play a key role in cell-to-cell communication by transferring their cargo to target tissues. Little is known on the course of exosome size and number in infants and children. Methods: Longitudinally, we assessed the size and number of circulating exosomes at birth and at ages 2 and 7 yr in 75 infants/children born appropriate-for-gestational-age (AGA; n=40) or small-for-gestational-age (SGA; n=35 with spontaneous catch-up), and related those results to concomitantly assessed measures of endocrine-metabolic health (HOMA-IR; IGF-1), body composition (by DXA at ages 0 and 2) and abdominal fat partitioning (subcutaneous, visceral and hepatic fat by MRI at age 7). Results: Circulating exosomes of AGAs decreased in size (on average by 4.2%) and increased in number (on average by 77%) between birth and age 7. Circulating exosomes of SGAs (as compared to those of AGAs) had a larger size at birth [146.8 vs 137.8 nm, respectively; p=0.02], and were in lower number at ages 2 [4.3x1011 vs 5.6x1011 particles/mL, respectively; p=0.01] and 7 [6.3x1011 vs 6.8x1011 particles/mL, respectively; p=0.006]. Longitudinal changes were thus more pronounced in SGAs for exosome size, and in AGAs for exosome number. At age 7, exosome size associated (P<0.0001) to liver fat in the whole study population. Conclusion: Early-life changes in circulating exosomes include a minor decrease in size and a major increase in number, and these changes may be influenced by fetal growth. Exosome size may become one of the first circulating markers of liver fat in childhood.
Subject(s)
Exosomes , Infant , Infant, Newborn , Child , Female , Humans , Infant, Small for Gestational Age , Body Composition , Liver/diagnostic imaging , Fetal DevelopmentABSTRACT
BACKGROUND: A "mismatch" sequence of less prenatal weight gain and more postnatal weight gain may lead to ectopic lipid accumulation, and trigger the development of early adrenarche/pubarche and the activation of the gonadotropic axis resulting in early puberty and ending up in full-blown adolescent polycystic ovary syndrome (PCOS). In the present study, we assess whether a low-dose combination of generics that collectively reduce ectopic fat through different pathways can slow down the accelerated maturation in "mismatch" girls with early puberty. METHODS: Randomized, placebo-controlled, multicenter, phase 2a, study in 64 girls [age, 8.0-9.3 years; birthweight (BW) for gestational age in lower tertile (-1.96< Z-score <-0.44), body mass index (BMI) in upper tertile (+0.44< Z-score < +1.96) and early progressive puberty (Tanner B2 at 7.7-9.0 years)]. Pharmacological intervention will be with a half-dose version of SPIOMET (mini-spiomet), a combination that reverts the PCOS phenotype in "mismatch" adolescents; mini-spiomet will contain spironolactone (25 mg/day, to raise brown adipose tissue activity), pioglitazone (3.75 mg/day, to raise adiponectin and insulin sensitivity), and metformin (425 mg/day, to raise AMPK activity and GDF15). Recruitment: 1 year; double-blind treatment: 1 year; open follow-up: 1 year; analyses and reporting: 1 year. INTERVENTIONS: randomization (1:1) for placebo vs mini-spiomet. PRIMARY OUTCOME: annualized bone age advancement (0-1 year) by BoneXpert; secondary outcomes: insulin, IGF-I, high-molecular-weight adiponectin (HMW-adip), sex hormone binding globulin (SHBG), ultra-sensitive C-reactive protein (usCRP), androgens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol, growth-and-differentiation factor 15 (GDF15), C-X-C motif chemokine ligand-14 (CXCL14), safety parameters, and quantification of hepato-visceral fat. DISCUSSION: The present study, if successful, may provide a first proof of the concept that the rapid maturation of girls with an upward mismatch between pre- and post-natal weight gain can be slowed down with a fixed low-dose combination of old and safe generics jointly targeting a reduction of ectopic fat without necessarily lowering body weight. TRIAL REGISTRATION: EudraCT 2021-006766-21. Registered on May 30, 2022.
Subject(s)
Metformin , Polycystic Ovary Syndrome , Humans , Female , Hypoglycemic Agents/therapeutic use , Adiponectin , Metformin/therapeutic use , Polycystic Ovary Syndrome/complications , Puberty , Weight Gain , Randomized Controlled Trials as Topic , Multicenter Studies as TopicABSTRACT
Objective: Bone morphogenetic protein-8B (BMP8B) is an adipokine produced by brown adipose tissue (BAT) contributing to thermoregulation and metabolic homeostasis in rodent models. In humans, BAT activity is particularly relevant in newborns and young infants. We assessed BMP8B levels and their relationship with BAT activity and endocrine-metabolic parameters in young infants to ascertain its potentiality as biomarker in early life. Materials and Methods: BMP8B concentrations were assessed longitudinally by ELISA in a cohort of 27 girls and 23 boys at birth, and at age 4 and 12 months, together with adiposity parameters (DXA), and circulating endocrine-metabolic variables. BAT activity was measured by infrared thermography. BMP8B gene expression (qRT-PCR) was determined in BAT, white fat, and liver samples from neonatal necropsies, and in placenta and cord blood. Results: BMP8B levels were high at birth, particularly in boys (P = 0.04 vs. girls), declined progressively, and remained well above those in healthy adults and pregnant women at age 1 year (P < 0.05 and P < 0.001, respectively). Neonatal BMP8B transcript levels were higher in BAT than in white fat, liver and cord blood. Circulating BMP8B levels during the first year of life marginally correlated with bone mineral density and gains in lean mass. Conclusion: BMP8B levels are high at birth and decline progressively over the first year of life remaining above adult levels. Although changes in BMP8B concentrations overall reflect those in BAT activity during development, BMP8B levels are unlikely to be useful to predict individual variations in endocrine-metabolic status and BAT activity in healthy young infants.
ABSTRACT
Okur-Chung neurodevelopmental syndrome (OCNS, MIM#617062) is a rare autosomal dominant syndrome related to CSNK2A1 mutations. It is characterized by intellectual disability, hypotonia, feeding and speech difficulties, dysmorphic features, and multisystem involvement. To date, less than 30 patients with OCNS have been described in detail in the literature, primarily in Asian populations. Here, we report a 5-year-old Spanish female with OCNS arising from a novel CSNK2A1 mutation c.149A>G, p.Tyr50Cys. Although her clinical features were compatible with OCNS syndrome, magnetic resonance imaging unexpectedly showed a duplication of the pituitary gland, a clinical finding not previously related to any known genetic condition. Other novel signs were an absence of the olfactory bulbs and multiple duplications of cervical vertebrae. We suggest that the midline abnormalities may be a significant part of this condition and lead to diagnostic suspicion. However, further descriptions are needed.
Subject(s)
Intellectual Disability/genetics , Musculoskeletal Abnormalities/genetics , Neurodevelopmental Disorders/genetics , Casein Kinase II/genetics , Child, Preschool , Female , Humans , Intellectual Disability/diagnosis , Musculoskeletal Abnormalities/diagnosis , Musculoskeletal Abnormalities/pathology , Mutation/genetics , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/pathology , Olfactory Bulb/pathology , Pituitary Gland/pathologyABSTRACT
No disponible
Subject(s)
Humans , Infant , Male , Head Injuries, Penetrating/classification , Head Injuries, Penetrating/epidemiology , Head Injuries, Penetrating/prevention & control , Emergencies/classification , Emergencies/epidemiology , Head Injuries, Penetrating/physiopathology , Head Injuries, Penetrating , Glasgow Coma Scale/trends , Skull/pathology , Skull , Tomography , Emergency Service, HospitalABSTRACT
CONTEXT AND OBJECTIVE: Children born small for gestational age (SGA) tend to become hyperinsulinemic and viscerally adipose and to have low levels of circulating high-molecular-weight (HMW) adiponectin upon completion of catch-up growth. We studied whether the same applies to SGA children, who failed to develop spontaneous catch-up growth. SETTING: The study was conducted at a university hospital. PATIENTS: Patients included 24 short SGA children (11 girls, 13 boys; mean age 7.5 yr, height -3.0 SD) as compared with appropriate-for-gestational-age (AGA) children (n = 32) and catch-up SGA children (n = 32) of similar height, weight, and body mass index. MAIN OUTCOMES: We measured fasting serum glucose, insulin, IGF-I, and HMW adiponectin; body composition by absorptiometry; and abdominal fat partitioning by magnetic resonance imaging. RESULTS AND CONCLUSION: Short SGA children were highly sensitive to insulin (P < 0.001 vs. AGA; P < 0.0001 vs. catch-up SGA), had low IGF-I levels, and had high-normal levels of HMW adiponectin (mean 14.0 vs. 7.4 mg/liter in catch-up SGA; P < 0.001). In the abdominal region, short SGA children had a normal amount of visceral fat (mean 17 vs. 18 cm(2) in AGA), but their sc fat was strikingly reduced (mean 18 vs. 29 cm(2) in AGA; P < 0.0001); this combination resulted in a markedly elevated ratio of visceral over sc fat (P < 0.0001 vs. AGA). The effects of GH therapy on these features of short SGA children remain to be studied.
Subject(s)
Abdominal Fat/metabolism , Body Composition , Body Height , Growth Disorders/metabolism , Infant, Small for Gestational Age , Adiponectin/blood , Child , Female , Human Growth Hormone/deficiency , Human Growth Hormone/therapeutic use , Humans , Infant, Newborn , Insulin-Like Growth Factor I/analysis , Male , Molecular WeightABSTRACT
No disponible
Subject(s)
Male , Female , Child , Humans , Multiple Trauma/epidemiology , Accidents/statistics & numerical data , Risk FactorsABSTRACT
Fundamento. El síndrome de distrés respiratorio agudo (SDRA) es una patología infrecuente pero con una elevada mortalidad pesar de los avances terapéuticos. En la literatura pediátrica se describe la utilidad pronostica de la diferencia alveolo-arterial de oxígeno DA-aO2 al inicio del SDRA para detectar los pacientes que fallecerán. El valor de DA-aO2 superior a 420 mmHg durante más de 16 horas es uno de los criterios aceptados de alta mortalidad y por tanto en algunos centros se utiliza para seleccionar a los pacientes candidatos a oxigenación extracorpórea por membrana (ECMO).Objetivos. 1) Describir la incidencia y curso evolutivo del SDRA en los pacientes ingresados en una UCI pediátrica.2) Valorar la respuesta a la utilización de PEEP > 5 cm H2O de los índices de oxigenación. 3) Evaluar la validez pronostica de los índices de oxigenación en las primeras 48 horas del diagnóstico de SDRA para la supervivencia de nuestros pacientes. Métodos. Estudio retrospectivo entre enero 1995 y mayo 2000 de pacientes con SDRA y edad entre un mes y 18 años ingresados en UCIP. Se calculan los índices de oxigenación, diferencia alveolo-arterial de oxígeno DA-aO2 i índice arterio-alveolar de oxígeno IA-aO2 antes y después de utilizar PEEP superiores a 5 cm H2O. Se relacionan los índices de oxigenación iniciales y a las 48 horas con el pronóstico de éxitos. Resultados. Se incluyen un total de 20 pacientes. En 12 pacientes la causa del SDRA es una bronconeumonía infecciosa, en 6 una sepsis, un caso de neumonía aspirativa y uno de contusión pulmonar. Tras la utilización de PEEP > 5 el índice PaO2/FiO2 aumenta con significación estadística (p 420 mmHg no es predictor de mortalidad. Conclusiones. 1) La utilización de PEEP elevada mejora el índice PaO2/FiO2. 2) El valor inicial de DA-aO2 no permite identificar a los pacientes supervivientes en nuestra población (AU)
Subject(s)
Adolescent , Female , Child, Preschool , Infant , Male , Child , Humans , Extracorporeal Membrane Oxygenation , Respiratory Insufficiency/therapy , Patient Selection , Intensive Care Units, Pediatric/statistics & numerical data , Respiratory Care Units/statistics & numerical data , Retrospective Studies , Hypoxia/physiopathology , Positive-Pressure RespirationABSTRACT
No disponible
