Obesidad en la infancia y adolescencia

En la actualidad, la obesidad se considera un problema de salud pública mundial dado el aumento de su prevalencia, su continuidad en la edad adulta, los cambios en los estilos de vida de la población, la comorbilidad que se asocia y la baja percepción del riesgo por parte de la población. La prevalencia actual de obesidad infantojuvenil en nuestro país se estima en un 12,6%. Determinados sujetos pueden tener una mayor predisposición genética a aumentar de peso, y los genes pueden no expresarse totalmente hasta la etapa adulta. A continuación, se aborda: la etiopatogenia multifactorial, la comorbilidad, así como el abordaje diagnóstico, terapéutico y la prevención que debe iniciarse en edades precoces, ya que los hábitos de salud se establecen en la infancia y posteriormente será difícil modificarlos. El diagnóstico es fundamentalmente clínico. El tratamiento es multidisciplinar, actuando sobre el paciente y su entorno. El pediatra tiene un papel importante detectando los factores y poblaciones de riesgo, colaborando en el tratamiento y ejerciendo una acción preventiva educadora en los diferentes niveles: familiar, escolar, social y políticoObesity is considered a worldwide public health problem given its increasing prevalence, its continuation into adulthood, society´s lifestyle changes, the associated comorbidities and society´s low perception of its risk. Spain´s current estimated prevalence among children and adolescents is 12.6%. Certain individuals have a higher genetic predisposition to gain weight, although the genes involved may not be fully expressed until adult age. This review includes the multifactorial pathogenesis, comorbidities, diagnostic and therapeutic approaches, and prevention strategies. The latter ought to be commenced in early ages as health habits are established during infancy, hence the difficulty in modifying these at a later stage. The diagnosis remains mainly clinical. The management requires a multidisciplinary intervention over the patient and their environment. The pediatrician has a significant role in identifying risk factors and at-risk individuals, participating in treatment and conducting preventive educational actions at different levels such as family, school, social and politica

What is a normal blood glucose?

Glucose is the key metabolic substrate for tissue energy production. In the perinatal period the mother supplies glucose to the fetus and for most of the gestational period the normal lower limit of fetal glucose concentration is around 3 mmol/L. Just after birth, for the first few hours of life in a normal term neonate appropriate for gestational age, blood glucose levels can range between 1.4 mmol/L and 6.2 mmol/L but by about 72 h of age fasting blood glucose levels reach normal infant, child and adult values (3.5-5.5 mmol/L). Normal blood glucose levels are maintained within this narrow range by factors which control glucose production and glucose utilisation. The key hormones which regulate glucose homoeostasis include insulin, glucagon, epinephrine, norepinephrine, cortisol and growth hormone. Pathological states that affect either glucose production or utilisation will lead to hypoglycaemia. Although hypoglycaemia is a common biochemical finding in children (especially in the newborn) it is not possible to define by a single (or a range of) blood glucose value/s. It can be defined as the concentration of glucose in the blood or plasma at which the individual demonstrates a unique response to the abnormal milieu caused by the inadequate delivery of glucose to a target organ (eg, the brain). Hypoglycaemia should therefore be considered as a continuum and the blood glucose level should be interpreted within the clinical scenario and with respect to the counter-regulatory hormonal responses and intermediate metabolites

Síndrome metabólico

El síndrome metabólico es un conjunto de factores de riesgo, que requieren la presencia de obesidad de predominio central, dislipemia, hipertensión arterial y resistencia a la insulina, todos ellos, predictores de enfermedad cardiovascular y diabetes tipo 2 en el futuro. La mayoría de los estudios demuestran que la prevalencia de síndrome metabólico es dependiente de las definiciones utilizadas, observando una prevalencia mayor en la región mediterránea que en la zona central y norte de Europa. Dentro de los mecanismos fisiopatológicos, uno de los principales es la resistencia a la insulina. La determinación de la glucemia y la insulina en ayunas son necesarias para identificar las alteraciones de la homeostasis de la glucemia, y reflejan fundamentalmente la secreción de insulina y la sensibilidad hepática y periférica. El tratamiento del síndrome metabólico comprende, en primer lugar, la realización de una dieta adecuada que tiene como objetivo mejorar la sensibilidad a la insulina y prevenir o corregir las alteraciones metabólicas y cardiovasculares asociadas. Asimismo, se debe acompañar de la realización de ejercicio físico regular y un adecuado soporte psicológico. En las alteraciones de la tolerancia a la glucemia, la modificación de los estilos de vida mejora, tanto la glucemia como los factores de riesgo cardiovascular. A menudo, hay que recurrir al tratamiento farmacológico, ya que los cambios en el estilo de vida son, a veces, complicados en los adolescentes. Por último, las estrategias para la prevención de la obesidad y el síndrome metabólico deben iniciarse en Atención Primaria, con programas dirigidos al ambiente familiar del niño con riesgo de obesidad y con programas desarrollados en el medio escolarMetabolic syndrome is a combination of risk factors, namely centrally distributed obesity, dyslipidemia, hypertension and insulin resistance, all of which are future predisposing factors for cardiovascular disease and type 2 diabetes. Most studies demonstrate that the prevalence of metabolic syndrome depends on the employed definition, and show a higher prevalence in the Mediterranean region than in north and central Europe. One of the main pathophysiological mechanisms is insulin resistance. Fasting glucose and insulin determinations are needed to detect abnormalities in glucose homeostasis, and indicate the secretion of insulin and its sensitivity in liver and peripheral tissues. The management of metabolic syndrome initially involves implementing an appropriate diet that leads to amelioration of the sensitivity to insulin and prevention/modification of the associated metabolic and cardiovascular abnormalities. This must be combined with regular exercise and adequate psychological support. In impaired glucose tolerance, the modification of life style will positively impact glycaemia and cardiovascular risk factors. Given the difficulty in modifying the lifestyle among adolescents, medication may need to be employed. Lastly, he strategies to prevent obesity and metabolic syndrome need to be initiated in the primary care setting, with programmes for families of children at risk of obesity, and with programmes implemented in school

Síndrome metabólico en la infancia y en la adolescencia

El síndrome metabólico es el conjunto de factores de riesgo relacionados con la obesidad, dislipemia, hipertensión arterial, resistencia a la insulina, y los estados infl amatorios, protrombóticos y aterogénicos, todos ellos predictores de enfermedad cardiovascular. La mayoría de los estudios demuestran que la prevalencia del síndrome metabólico es dependiente de las defi niciones utilizadas. Los mecanismos fi siopatológicos en niños han sido poco investigados, siendo uno de los principales la resistencia a la insulina. La determinación de la glucemia y la insulina en ayunas son necesarios para identifi car las alteraciones de la homeostasis de la glucemia y refl ejan, fundamentalmente, la secreción de insulina y la sensibilidad hepática y periférica. El tratamiento comprende, en primer lugar, la realización de una dieta adecuada que tiene como objetivo mejorar la sensibilidad a la insulina y prevenir o corregir las alteraciones metabólicas y cardiovasculares asociadas. Asimismo, se debe acompañar de la realización de ejercicio físico regular y un adecuado soporte psicológico. Para el tratamiento farmacológico de la obesidad grave, disponemos de algunos fármacos, siendo aún su indicación limitada en la adolescencia. En las alteraciones de la tolerancia a la glucemia, la modifi cación de los estilos de vida mejoran tanto la glucemia como los factores de riesgo cardiovascular. A menudo, hay que recurrir al tratamiento farmacológico, ya que los cambios en el estilo de vida son, a veces, complicados en los adolescentes. Por último, las estrategias para la prevención de la obesidad y el síndrome metabólico deben iniciarse en Atención Primaria, con programas dirigidos al ambiente familiar del niño con riesgo de obesidad y con programas desarrollados en el medio escolarThe metabolic syndrome is a combination of risk factors related with obesity, dyslipidemia, high blood pressure, insulin resistance, and infl ammatory, prothrombotic and atherogenic states, all of these predictors of cardiovascular disease. Most of the studies show that the prevalence of the metabolic syndrome is dependent on the defi nitions used. The pathophysiological mechanisms in children have not been demonstrated much, one of the principal ones being insulin resistance. Measurement of fasting glucose and insulin are necessary to identify the alterations of glucose homeostasis and fundamentally refl ect insulin secretion and hepatic and peripheral sensitivity. Treatment includes, in the fi rst place, adequate diet whose objective is to improve sensitivity to insulin and prevent or correct associated metabolic and cardiovascular disorders. In addition, it should be accompanied by regular physical exercise and adequate psychological support. Some drugs are available for their pharmacological treatment of severe obesity, their indications still being limited in adolescence. In glucose tolerability alterations, modifi cations of style of life improves spoke glucose and cardiovascular risk factors. It is often necessary to resort to drug treatment, since changes in style of life are sometimes complicated in adolescence. Finally, the strategies for the prevention of obesity on metabolic syndrome should be initiated in Primary Care, with programs aimed at the family environment of the child with risk of obesity and with programs developed in the school settin

Endocrine morbidity in midline brain defects: Differences between septo-optic dysplasia and related disorders

Background Septo-optic dysplasia (SOD) is a heterogeneous congenital condition. The aim of this study was to investigate the clinical phenotypes of a large cohort of children with SOD, Multiple Pituitary Hormone Deficiency (MPHD) and Optic Nerve Hypoplasia (ONH), with a focus on endocrine testing. Methods Retrospective single-centre longitudinal study of children with SOD (n:171), MPHD (n:53) and ONH (n:35). SOD+ and SOD- indicate patients with or without hypopituitarism, respectively. Findings All deficits were more frequent and occurred earlier in MPHD than SOD+ [Hazard Ratios (HR): 0·63(0·45,0·89) for GH, 0·48(0·34,0·69) for TSH, 0·55(0·38,0·80) for ACTH, 0·28(0·11,0·68) for gonadotropins], except Diabetes Insipidus (DI) [HR: 2·27(0·88,5·9)]. Severe hypothalamo-pituitary (H-P) abnormalities were more frequent in MPHD [80·0% vs 41·6%, p<0·0001 for Ectopic Posterior Pituitary (EPP)]. Stalk and PP abnormalities were associated with more severe endocrine phenotypes and placed a subgroup of SOD+ at risk of developing deficits earlier. SOD and ONH shared heterogeneous phenotypes ranging from pubertal delay to precocity and from leanness to extreme obesity, whilst MPHD had GnD and obesity only. Mortality was recorded in 4·2% (6/144) SOD and 3·2% (1/31) ONH, and only in patients with multisystem phenotypes. Interpretation More than a single disease, SOD represents a spectrum of malformative conditions involving different brain structures and characterised by a dynamic and sequential nature of endocrine. In contrast, MPHD displays a more homogeneous phenotype of (mainly) anterior pituitary early-onset failure. Stalk and PP abnormalities place a subgroup of SOD+ at a higher risk of early-onset deficits. Additionally, there are striking differences between the SOD and MPHD cohorts in terms of pubertal progression. The shared phenotypes between ONH and SOD could be partly explained by common hypothalamic dysfunction. The differences between the cohorts are important as they may aid in planning management and preventing morbidity by dictating earlier interventions

Sensibilidad de las variaciones en el campo de deformaciones en función de la aparición de daños en palas de aerogeneradores fabricadas en materiales compuestos

Se instrumentó un prototipo de pala de aerogenerador de 150 kW de 13 metros de longitud con 24 FBGs embebidas directamente en el material durante la fabricación. Posteriormente se realizaron mediciones de deformaciones en el prototipo de pala sin ningún daño, con el fin de determinar el baseline de la pala. Luego, se indujeron algunos daños artificiales de diferentes naturalezas y severidades con el fin de estudiar la susceptibilidad de la aparición de cambios en el campo de deformaciones y la rigidez global de la pala, en función de la aparición de dichos daños. Se realizó un estudio de esfuerzos diferenciales con el fin de determinar la variación de la rigidez en la estructura y determinar si los sensores embebidos eran capaces de detectar dicha variación. Los resultados se presentan en este artículo

Noninvasive assessment of an engineered bioactive graft in myocardial infarction: impact on cardiac function and scar healing

Cardiac tissue engineering, which combines cells and biomaterials, is promising for limiting the sequelae of myocardial infarction (MI). We assessed myocardial function and scar evolution after implanting an engineered bioactive impedance graft (EBIG) in a swine MI model. The EBIG comprises a scaffold of decellularized human pericardium, green fluorescent protein-labeled porcine adipose tissue-derived progenitor cells (pATPCs), and a customized-design electrical impedance spectroscopy (EIS) monitoring system. Cardiac function was evaluated noninvasively by using magnetic resonance imaging (MRI). Scar healing was evaluated by using the EIS system within the implanted graft. Additionally, infarct size, fibrosis, and inflammation were explored by histopathology. Upon sacrifice 1 month after the intervention, MRI detected a significant improvement in left ventricular ejection fraction (7.5%64.9% vs. 1.4%63.7%; p = .038) and stroke volume (11.565.9 ml vs. 364.5 ml; p = .019) in EBIG-treated animals. Noninvasive EIS data analysis showed differences in both impedance magnitude ratio (20.02 6 0.04 per day vs. 20.48 6 0.07 per day; p = .002) and phase angle slope (20.18°60.24° per day vs.23.52°60.84° per day; p = .004) in EBIG compared with control animals. Moreover, in EBIG-treated animals, the infarct size was 48% smaller (3.4%60.6% vs. 6.5%61%; p = .015), less inflammation was found by means of CD25+ lymphocytes (0.65 6 0.12 vs. 1.26 6 0.2; p = .006), and a lower collagen I/III ratio was detected (0.4960.06 vs. 1.6660.5; p = .019). An EBIG composed of acellular pericardium refilled with pATPCs significantly reduced infarct size and improved cardiac function in a preclinical model of MI. Noninvasive EIS monitoring was useful for tracking differential scar healing in EBIG-treated animals, which was confirmed by less inflammation and altered collagen deposit.Peer ReviewedPostprint (published version

Syndromic Forms of Hyperinsulinaemic Hypoglycaemia A 15-year follow-up Study

OBJECTIVE: Hyperinsulinaemic hypoglycaemia (HH) is one of the commonest causes of hypoglycaemia in children. The molecular basis includes defects in pathways that regulate insulin release. Syndromic conditions like Beckwith-Wiedemann (BWS), Kabuki (KS) and Turner (TS) are known to be associated with a higher risk for HH. This systematic review of children with HH referred to a tertiary centre aims at estimating the frequency of a syndromic/multisystem condition to help address stratification of genetic analysis in infants with HH. METHODS: We performed a retrospective study of 69 patients with syndromic features and hypoglycaemia in a specialist centre from 2004 to 2018. RESULTS: Biochemical investigations confirmed HH in all the cases and several genetic diagnoses were established. Responsiveness to medications and the final outcome following medical treatment or surgery were studied. CONCLUSIONS: This study highlights the association of HH with a wide spectrum of syndromic diagnoses and that children with features suggestive of HH-associated syndromes should be monitored for hypoglycaemia. If hypoglycaemia is documented, they should also be screened for possible HH. Our data indicate that most syndromic forms of HH are diazoxide-responsive and that HH resolves over time; however a significant percentage continues to require medications years after the onset of the disease. Early diagnosis of hyperinsulinism and initiation of treatment is important for preventing hypoglycaemic brain injury and intellectual disability

Sensing the turbulent large-scale motions with their wall signature

This study assesses the capability of extended proper orthogonal decomposition (EPOD) and convolutional neural networks (CNNs) to reconstruct large-scale and very-large-scale motions (LSMs and VLSMs respectively) employing wall-shear-stress measurements in wall-bounded turbulent flows. Both techniques are used to reconstruct the instantaneous LSM evolution in the flow field as a combination of proper orthogonal decomposition (POD) modes, employing a limited set of instantaneous wall-shear-stress measurements. Due to the dominance of nonlinear effects, only CNNs provide satisfying results. Being able to account for nonlinearities in the flow, CNNs are shown to perform significantly better than EPOD in terms of both instantaneous flow-field estimation and turbulent-statistics reconstruction. CNNs are able to provide a more effective reconstruction performance employing more POD modes at larger distances from the wall and employing lower wall-measurement resolutions. Furthermore, the capability of tackling nonlinear features of CNNs results in estimation capabilities that are weakly dependent on the distance from the wall.This work has been partially supported by Grant No. DPI2016-79401-R funded by the Spanish State Research Agency (SRA) and the European Regional Development Fund (ERDF). A.G. acknowledges Dr. A. Sánchez for insightful discussions about CNN architecture. The authors acknowledge Dr. R. Vinuesa for insightful comments and discussions

Liver tissue remodeling following ablation with irreversible electroporation in a porcine model

Irreversible electroporation (IRE) is a method of non-thermal focal tissue ablation characterized by irreversibly permeabilizing the cell membranes while preserving the extracellular matrix. This study aimed to investigate tissue remodeling after IRE in a porcine model, especially focusing on the extracellular matrix and hepatic stellate cells. IRE ablation was performed on 11 female pigs at 2,000 V/cm electric field strength using a versatile high-voltage generator and 3 cm diameter parallel-plate electrodes. The treated lobes were removed during surgery at 1, 3, 7, 14, and 21 days after IRE. Tissue remodeling and regeneration were assessed by histopathology and immunohistochemistry. Throughout the treated area, IRE led to extensive necrosis with intact collagenous structures evident until day 1. From then on, the necrosis progressively diminished while reparative tissue gradually increased. During this process, the reticulin framework and the septal fibrillar collagen remained in the necrotic foci until they were invaded by the reparative tissue. The reparative tissue was characterized by a massive proliferation of myofibroblast-like cells accompanied by a complete disorganization of the extracellular matrix with the disappearance of hepatic architecture. Hepatic stellate cell markers were associated with the proliferation of myofibroblast-like cells and the reorganization of the extracellular matrix. Between 2 and 3 weeks after IRE, the lobular architecture was almost completely regenerated. The events described in the present study show that IRE may be a valid model to study the mechanisms underlying liver regeneration after extensive acute injury