Proteomic analysis of exosomes derived from human mature milk and colostrum of mothers with term, late preterm, or very preterm delivery.

The growth and development of the human brain is a long and complex process that requires a precise sequence of genetic and molecular events. This begins in the third week of gestation with the differentiation of neural progenitor cells and extends at least until late adolescence, possibly for life. One of the defects of this development is that we know very little about the signals that modulate this sequence of events. The first 3 years of life, during breastfeeding, is one of the critical periods in brain development. In these first years of life, it is believed that neurodevelopmental problems may be the molecular causes of mental disorders. Therefore, we herein propose a new hypothesis, according to which the chemical signals that could modulate this entire complex sequence of events appear in this early period, and the molecular level study of human breast milk and colostrum of mothers who give birth to children in different gestation periods could give us information on proteins influencing this process. In this work, we collected milk and colostrum samples (term, late preterm and moderate/very preterm) and exosomes were isolated. The samples of exosomes and complete milk from each fraction were analyzed by LC-ESI-MS/MS. In this work, we describe proteins in the different fractions of mature milk and colostrum of mothers with term, late preterm, or very preterm delivery, which could be involved in the regulation of the nervous system by their functions. We describe how they differ in different types of milk, paving the way for the investigation of possible new neuroregulatory pathways as possible candidates to modulate the nervous system.

Human Breast Milk microRNAs, Potential Players in the Regulation of Nervous System.

Human milk is the biological fluid with the highest exosome amount and is rich in microRNAs (miRNAs). These are key regulators of gene expression networks in both normal physiologic and disease contexts, miRNAs can influence many biological processes and have also shown promise as biomarkers for disease. One of the key aspects in the regeneration of the nervous system is that there are practically no molecules that can be used as potential drugs. In the first weeks of lactation, we know that human breast milk must contain the mechanisms to transmit molecular and biological information for brain development. For this reason, our objective is to identify new modulators of the nervous system that can be used to investigate neurodevelopmental functions based on miRNAs. To do this, we collected human breast milk samples according to the time of delivery and milk states: mature milk and colostrum at term; moderate and very preterm mature milk and colostrum; and late preterm mature milk. We extracted exosomes and miRNAs and realized the miRNA functional assays and target prediction. Our results demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function. We found 132 different miRNAs were identified across all samples. Sixty-nine miRNAs had significant differential expression after paired group comparison. These miRNAs are implicated in gene regulation of dopaminergic/glutamatergic synapses and neurotransmitter secretion and are related to the biological process that regulates neuron projection morphogenesis and synaptic vesicle transport. We observed differences according to the delivery time and with less clarity according to the milk type. Our data demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function.

Effects of Hypothermia and Allopurinol on Oxidative Status in a Rat Model of Hypoxic Ischemic Encephalopathy.

Hypoxic ischemic encephalopathy (HIE) is one of the main causes of morbidity and mortality during the neonatal period, despite treatment with hypothermia. There is evidence that oxidative damage plays an important role in the pathophysiology of hypoxic-ischemic (HI) brain injury. Our aim was to investigate whether postnatal allopurinol administration in combination with hypothermia would reduce oxidative stress (OS) biomarkers in an animal model of HIE. Postnatal 10-day rat pups underwent unilateral HI of moderate severity. Pups were randomized into: Sham operated, hypoxic-ischemic (HI), HI + allopurinol (HIA), HI + hypothermia (HIH), and HI + hypothermia + allopurinol (HIHA). Biomarkers of OS and antioxidants were evaluated: GSH/GSSG ratio and carbonyl groups were tested in plasma. Total antioxidant capacity (TAC) was analyzed in plasma and cerebrospinal fluid, and 8-iso-prostaglandin F2α was measured in brain tissue. Plasma 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) levels were preserved in those groups that received allopurinol and dual therapy. In cerebrospinal fluid, only the HIA group presented normal ferric reducing ability of plasma (FRAP) levels. Protein oxidation and lipid peroxidation were significantly reduced in all groups treated with hypothermia and allopurinol, thus enhancing neuroprotection in HIE.

Drug testing in biological samples vs. maternal surveys for the detection of substance use during whole pregnancy.

BACKGROUND: Early diagnosis of nicotine, ethanol and drug use during pregnancy is critical in order to provide adequate care. Current screening procedures show limitations in terms of reliability and short windows of detection. OBJECTIVES: To investigate the prevalence and identify biomarkers of substance use and changes in substance use during pregnancy. To compare drug testing results in different types of biological samples (maternal hair, meconium, placenta, umbilical-cord) with self-reported data. PARTICIPANTS AND SETTING: Prospective cohort study using data from pregnant women and their newborns. METHODS: Biological matrices were collected at birth and analyzed by liquid chromatography tandem mass spectrometry. A paper survey was provided to determine substance use habits. RESULTS: 867 mother-newborn pairs were included. According to the analysis of biological samples, 29.1% cases were positive for one or more substances (13.6% nicotine, 8.4% ethanol, 8.3% cocaine, 6.4% cannabis, 5.7% opioids). The profile of the substance-using mother was a single woman, <28 years-old, with no higher education and unemployed. Segmental maternal hair analysis showed a decrease in tobacco, cannabis and cocaine use throughout pregnancy (p < 0.001). The level of concordance between results from interviews and from biological analyses was weak for opioids, cocaine, and cannabis (kappa coefficient < 0.40). Maternal hair detected the highest number of cases, followed by meconium and by placenta and/or umbilical-cord. CONCLUSIONS: Maternal survey was not a reliable screening technique. Analysis of maternal hair detected the highest number of cases with the broadest detection window (whole pregnancy).

Tumoraciones post-contusión... ¿es necesario drenar? / Post-contusion tumours: Is it necessary to drain?

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Value of Fibrinogen to Discriminate Appendicitis from Nonspecific Abdominal Pain in Preschool Children.

INTRODUCTION: The aim of this study was to assess the diagnostic value of the biomarker fibrinogen (FB), along with the markers white blood cell (WBC) count, absolute neutrophil count (ANC), and C-reactive protein (CRP), to discriminate appendicitis from nonspecific abdominal pain (NSAP) in preschool children. MATERIALS AND METHODS: We prospectively evaluated all children aged <5 years admitted for suspected appendicitis at an academic pediatric emergency department during 5 years. Diagnostic accuracy of FB (prothrombin time-derived method), WBC, ANC, and CRP were assessed by the area under the curve (AUC) of the receiver-operating characteristic curve. RESULTS: A total of 82 patients were enrolled in the study (27 NSAP, 17 uncomplicated, and 38 complicated appendicitides). WBC and ANC had moderate diagnostic accuracy for appendicitis versus NSAP (WBC: AUC 0.66, ANC: AUC 0.67). CRP and FB had good diagnostic accuracy for appendicitis versus NSAP (CRP: AUC 0.78, FB: AUC 0.77). WBC and ANC are not useful to discriminate complicated versus uncomplicated appendicitis (WBC: AUC 0.43, ANC: AUC 0.45). CPR and FB had good diagnostic accuracy for complicated versus uncomplicated appendicitis (CRP: AUC 0.80, FB: AUC 0.73). CONCLUSION: CRP and FB are more useful than WBC and ANC to discriminate appendicitis from NSAP in preschool children. CRP and FB are especially useful to discriminate complicated from uncomplicated appendicitis and NSAP. In a child with suspected appendicitis, a plasma FB level (prothrombin time-derived method) >540 mg/dL is associated with an increased likelihood of complicated appendicitis.

The Practicality of Feeding Defatted Human Milk in the Treatment of Congenital Chylothorax.

Introduction: Congenital chylothorax (CC) is a rare and life-threating condition. Since its treatment is founded on the elimination of long-chain fatty acids from the diet, breastfeeding has been traditionally contraindicated. However, breast milk could be very beneficial due to its immunological and nutritional benefits. Only limited research has been published about the usage of modified-fat breast milk (MBM) in chylothorax treatment. Methods and Results: Systematic review methods were used by two independent reviewers. Only a few case report studies (quality assessment on the domains of the GRADE approach), two small controlled studies, a retrospective study, and some test-tube-based laboratory research met the inclusion criteria. Despite this, we have observed a widespread clinical adoption of this novel treatment in health institutions. Data suggest that modified-fat breast milk does facilitate the resolution of chylothoraces. Refrigerated centrifuge (2°C, 3,000 rpm for 15 minutes) and syringe fat removal methods were the most efficient options in terms of fat reduction. Conclusions: Feeding of human milk is advisable in CC and feasible by means of a simple milk defatting procedure. Open questions remain, related to length and degree of fat restriction and need for individualized fortification of defatted breast milk.

Topiramate plus Cooling for Hypoxic-Ischemic Encephalopathy: A Randomized, Controlled, Multicenter, Double-Blinded Trial.

BACKGROUND AND OBJECTIVES: Therapeutic interventions to improve the efficacy of whole-body cooling for hypoxic-ischemic encephalopathy (HIE) are desirable. Topiramate has been effective in reducing brain damage in experimental studies. However, in the clinical setting information is limited to a small number of feasibility trials. We launched a randomized controlled double-blinded topiramate/placebo multicenter trial with the primary objective being to reduce the antiepileptic activity in cooled neonates with HIE and assess if brain damage would be reduced as a consequence. STUDY DESIGN: Neonates were randomly assigned to topiramate or placebo at the initiation of hypothermia. Topiramate was administered via a nasogastric tube. Brain electric activity was continuously monitored. Topiramate pharmacokinetics, energy-related and Krebs' cycle intermediates, and lipid peroxidation biomarkers were determined using liquid chromatography-mass spectrometry and MRI for assessing brain damage. RESULTS: Out of 180 eligible patients 110 were randomized, 57 (51.8%) to topiramate and 53 (48.2%) to placebo. No differences in the perinatal or postnatal variables were found. The topiramate group exhibited less seizure burden in the first 24 h of hypothermia (topiramate, n = 14 [25.9%] vs. placebo, n = 22 [42%]); needed less additional medication, and had lower mortality (topiramate, n = 5 [9.2%] vs. placebo, n = 10 [19.2%]); however, these results did not achieve statistical significance. Topiramate achieved a therapeutic range in 37.5 and 75.5% of the patients at 24 and 48 h, respectively. A significant association between serum topiramate levels and seizure activity (p < 0.016) was established. No differences for oxidative stress, energy-related metabolites, or MRI were found. CONCLUSIONS: Topiramate reduced seizures in patients achieving therapeutic levels in the first hours after treatment initiation; however, they represented only a part of the study population. Our results warrant further studies with higher loading and maintenance dosing of topiramate.

Neurodevelopmental Disorders and Array-Based Comparative Genomic Hybridization: Sensitivity and Specificity using a Criteria Checklist for Genetic Test Performance.

BACKGROUND: Array-based comparative genomic hybridization (aCGH) is a molecular analysis method for identifying chromosomal anomalies or copy number variants (CNVs) correlating with clinical phenotypes. The aim of our study was to identify the most significant clinical variables associated with a positive outcome of aCGH analyses to develop a simple predictive clinical score. METHODS: We conducted a cross-sectional study in a tertiary center comparing the genotype and phenotype of the cases. A score was developed using multivariate logistic regression. The best score cutoff point, sensitivity, specificity, positive and negative predictive values, and area under the curve were calculated with the receiver operating characteristic curve. RESULTS: aCGH identified structural chromosomal alterations responsible for the disorder in 13.7% (95% confidence interval [CI]: 10.9-16.5) of our sample (570 patients analyzed by aCGH). Based on the most frequent phenotypic characteristics among patients with a pathogenic CNV, we have created a checklist with the following items: alteration of the cranial perimeter, stature < percentile (p) 3, weight < p3, presence of brain malformations, ophthalmological malformations, two or more dysmorphic features in the same patient, and autism spectrum disorder diagnosis. Using a score ≥1.5 as the cutoff point for the test, we obtained a sensitivity of 82.4% (95% CI: 73.1-91.8) and a specificity of 54.2% (95% CI: 49.7-58.7). CONCLUSION: All individuals with a score of 1.5 or higher should be genetically screened by aCGH. This approach can improve clinical indications for aCGH in patients with neurodevelopmental disorders, but the scoring system should be validated in an external group.

Estrés oxidativo en la asfixia perinatal y la encefalopatía hipóxico-isquémica / Oxidative stress in perinatal asphyxia and hypoxic-ischaemic encephalopathy

La asfixia intraparto es una de las causas más frecuentes de muerte neonatal precoz pero también puede, en los supervivientes, evolucionar a una encefalopatía hipóxico-isquémica responsable de una elevada morbilidad neurológica. La presencia de episodios de hipoxia-isquemia prolongados conduce a un rápido agotamiento energético en los tejidos exclusivamente dependientes del metabolismo aeróbico, como el sistema nervioso central. El déficit energético conlleva una paralización de las bombas ATP-dependientes y subsiguiente pérdida del potencial neuronal transmembrana. La población neuronal de las regiones más sensibles del SNC mueren por necrosis, mientras que en otras áreas se produce una hiperexcitabilidad neuronal con entrada masiva de calcio iónico, activación de NO-sintasa, generación de radicales libres que alteran el funcionamiento mitocondrial, provocando un fallo energético secundario y muerte neuronal por apoptosis. Recientemente se ha propuesto una tercera fase en la que factores como la inflamación persistente y los cambios epigenéticos causarían un bloqueo de la maduración de los oligodendrocitos, alteración de la neurogénesis, del crecimiento axonal y de la sinaptogénesis. En este contexto, el estrés oxidativo va a tener un papel protagonista como responsable tanto en causar daño directo al SNC como en activar cascadas metabólicas conducentes a la apoptosis e inflamación. La hipotermia moderada precoz, al preservar las reservas energéticas y disminuir la formación de especies reactivas de oxígeno, atenuará el daño cerebral posreanimación. La combinación de la hipotermia con terapias coadyuvantes para modular el estrés oxidativo podría contribuir a mejorar el pronóstico

Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis

Riesgo de displasia del desarrollo de la cadera en pacientes sometidos a versión cefálica externa / Risk of developmental dysplasia of the hip in patients subjected to the external cephalic version

Introducción: La displasia del desarrollo de la cadera (DDC) engloba un espectro de anomalías que afecta a la maduración y desarrollo de la cadera. La presentación podálica es uno de los factores de riesgo asociado a esta patología y puede ser modificada en las últimas semanas de gestación mediante la versión cefálica externa (VCE). El objetivo de nuestro trabajo es determinar la incidencia de DDC en pacientes sometidos a una VCE exitosa, así como valorar la necesidad de incluir a estos niños (podálicos durante gran parte de la gestación) en el protocolo de cribado de DDC. Material y métodos: Estudio de cohortes prospectivo realizado en el Hospital Universitario de Vigo entre el 1 de enero y el 31 de diciembre del 2015. Participaron niños sometidos a VCE y niños podálicos no sometidos a VCE. A todos ellos se les realizó una ecografía de cadera para estudiar la incidencia de DDC en ambos grupos. Resultados: Se incluyeron un total de 122 pacientes. Se intentó realizar VCE en 67 (54,9%) siendo exitosa en 35 (52,2%). De los 122 niños: 14 fueron diagnosticados de DDC mediante ecografía. Tres (8,5%) de los niños con DDC nacieron en presentación cefálica tras VCE exitosa con exploración física de caderas normal al nacimiento. Conclusiones: La VCE reduce el riesgo de DDC con respecto a la presentación podálica pero de no incluir a los niños versionados con éxito en el protocolo de cribado de DDC, corremos el riesgo de no detectar precozmente esta patología (AU)

Introduction: Developmental dysplasia of the hip (DDH) refers to the spectrum of abnormalities of maturation and development of the hip. Breech presentation is associated with DDH. This risk factor can be modified by external cephalic version (ECV). The aim of this study is to evaluate the incidence of DDH in patients who successfully underwent ECV, as well as to evaluate need for these children (breech for a period during gestation) to be included in the DDH screening protocol. Material and methods: A prospective cohort study was conducted in the Hospital Universitario de Vigo from January 1, 2015 to December 31, 2015. It included children born in cephalic presentation after a successful ECV, as well as children born in breech presentation. They all were screened for DDH by ultrasound examination of the hip. Results: Out of a total of 122 newborns included in the study, ECV was attempted on 67 (54.9%), of which 35 (52.2%) were successful. Out of the 14 children diagnosed with DDH, 3 of those born in cephalic presentation after a successful ECV were found to be normal on physical examination. Conclusions: Successful ECV is associated with a lower incidence of DDH as regards breech presentation. However, these patients should be included in the DDH screening protocol for the early detection of this disorder (AU)

Apendicitis versus dolor abdominal agudo inespecífico: evaluación del Pediatric Appendicitis Score / Appendicitis versus non-specific acute abdominal pain: Paediatric Appendicitis Score evaluation

Introducción: El dolor abdominal agudo inespecífico es el principal proceso que requiere diagnóstico diferencial con la apendicitis en la práctica clínica. El objetivo de este estudio es evaluar la utilidad del Pediatric Appendicitis Score (Regla de predicción clínica de apendicitis pediátrica) para diferenciar estas 2 entidades. Material y métodos: Se evaluó prospectivamente a los pacientes atendidos por sospecha de apendicitis en nuestro centro durante 2 años, incorporando al estudio casos de dolor abdominal agudo inespecífico y apendicitis. Se recogieron diferentes variables, incluyendo las que conforman el Score y la proteína C reactiva, que se analizaron estadísticamente de manera descriptiva, univariante y multivariante, y mediante pruebas de rendimiento diagnóstico (curvas ROC). Resultados: Se estudiaron 275 casos; 143 casos de dolor abdominal agudo inespecífico y 132 casos de apendicitis. La temperatura y el dolor a palpación en fosa iliaca derecha fueron las únicas variables que no mostraron diferencias significativas entre los grupos, careciendo de poder de discriminación. El dolor con la tos, el salto y/o la percusión fue la variable con mayor asociación a apendicitis. El Score estratificó correctamente a los pacientes en grupos de riesgo. La sustitución de la temperatura por la proteína C reactiva en el Score aumentaba su rendimiento diagnóstico, aunque sin diferencias significativas. Conclusiones: El Pediatric Appendicitis Score ayuda en el diagnóstico diferencial entre apendicitis y dolor abdominal agudo inespecífico. Sería recomendable la sustitución de la temperatura en el Score, pues carece de poder de discriminación entre estos grupos. La proteína C reactiva, categorizada en el valor 25,5 mg/L, podría ser utilizada en su lugar (AU)

Introduction: Non-specific acute abdominal pain is the most common process requiring differential diagnosis with appendicitis in clinical practice. The aim of this study was to assess the Paediatric Appendicitis Score in differentiating between these two entities. Material and methods: All patients admitted due to suspicion of appendicitis were prospectively evaluated in our hospital over a two-year period. Cases of non-specific acute abdominal pain and appendicitis were enrolled in the study. Several variables were collected, including Score variables and C-reactive protein levels. Descriptive, univariate and multivariate analyses and diagnostic accuracy studies (ROC curves) were performed. Results: A total of 275 patients were studied, in which there were 143 cases of non-specific acute abdominal pain and 132 cases of appendicitis. Temperature and right iliac fossa tenderness on palpation were the variables without statistically significant differences, and with no discrimination power between groups. Pain on coughing, hopping, and/or percussion tenderness in the right lower quadrant was the variable with greater association with appendicitis. The Score correctly stratified the patients into risk groups. Substitution of temperature for C-reactive protein in the Score increased diagnostic accuracy, although with no statistically significant differences. Conclusions: The Paediatric Appendicitis Score helps in differential diagnosis between appendicitis and non-specific acute abdominal pain. It would be advisable to replace the temperature in the Score, since it has no discrimination power between these groups. C-reactive protein at a cut-off value of 25.5 mg/L value could be used instead (AU)

[Oxidative stress in perinatal asphyxia and hypoxic-ischaemic encephalopathy]. / Estrés oxidativo en la asfixia perinatal y la encefalopatía hipóxico-isquémica.

Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis.

[Risk of developmental dysplasia of the hip in patients subjected to the external cephalic version]. / Riesgo de displasia del desarrollo de la cadera en pacientes sometidos a versión cefálica externa.

INTRODUCTION: Developmental dysplasia of the hip (DDH) refers to the spectrum of abnormalities of maturation and development of the hip. Breech presentation is associated with DDH. This risk factor can be modified by external cephalic version (ECV). The aim of this study is to evaluate the incidence of DDH in patients who successfully underwent ECV, as well as to evaluate need for these children (breech for a period during gestation) to be included in the DDH screening protocol. MATERIAL AND METHODS: A prospective cohort study was conducted in the Hospital Universitario de Vigo from January 1, 2015 to December 31, 2015. It included children born in cephalic presentation after a successful ECV, as well as children born in breech presentation. They all were screened for DDH by ultrasound examination of the hip. RESULTS: Out of a total of 122 newborns included in the study, ECV was attempted on 67 (54.9%), of which 35 (52.2%) were successful. Out of the 14 children diagnosed with DDH, 3 of those born in cephalic presentation after a successful ECV were found to be normal on physical examination. CONCLUSIONS: Successful ECV is associated with a lower incidence of DDH as regards breech presentation. However, these patients should be included in the DDH screening protocol for the early detection of this disorder.

[Appendicitis versus non-specific acute abdominal pain: Paediatric Appendicitis Score evaluation]. / Apendicitis versus dolor abdominal agudo inespecífico: evaluación del Pediatric Appendicitis Score.

INTRODUCTION: Non-specific acute abdominal pain is the most common process requiring differential diagnosis with appendicitis in clinical practice. The aim of this study was to assess the Paediatric Appendicitis Score in differentiating between these two entities. MATERIAL AND METHODS: All patients admitted due to suspicion of appendicitis were prospectively evaluated in our hospital over a two-year period. Cases of non-specific acute abdominal pain and appendicitis were enrolled in the study. Several variables were collected, including Score variables and C-reactive protein levels. Descriptive, univariate and multivariate analyses and diagnostic accuracy studies (ROC curves) were performed. RESULTS: A total of 275 patients were studied, in which there were 143 cases of non-specific acute abdominal pain and 132 cases of appendicitis. Temperature and right iliac fossa tenderness on palpation were the variables without statistically significant differences, and with no discrimination power between groups. Pain on coughing, hopping, and/or percussion tenderness in the right lower quadrant was the variable with greater association with appendicitis. The Score correctly stratified the patients into risk groups. Substitution of temperature for C-reactive protein in the Score increased diagnostic accuracy, although with no statistically significant differences. CONCLUSIONS: The Paediatric Appendicitis Score helps in differential diagnosis between appendicitis and non-specific acute abdominal pain. It would be advisable to replace the temperature in the Score, since it has no discrimination power between these groups. C-reactive protein at a cut-off value of 25.5mg/L value could be used instead.

Influence of catch up growth on spatial learning and memory in a mouse model of intrauterine growth restriction.

BACKGROUND: Intrauterine growth restriction (IUGR) and rapid postnatal weight gain or catch up growth (CUG) increase the susceptibility to metabolic syndrome during adult life. Longitudinal studies have also revealed a high incidence of learning difficulties in children with IUGR. The aim of the present study was to investigate the effect of nutrition and CUG on learning memory in an IUGR animal model. We hypothesized that synaptic protein expression and transcription, an essential mechanism for memory consolidation, might be affected by intrauterine undernutrition. METHODS: IUGR was induced by 50% maternal caloric undernutrition throughout late gestation. During the suckling period, dams were either fed ad libitum or food restricted. The pups were divided into: Normal prenatal diet-Normal postnatal diet (NN), Restricted prenatal diet- Normal postnatal diet + catch up growth (RN+), Normal prenatal diet-Restricted postnatal diet (NR) and Restricted prenatal diet-Restricted postnatal diet (RR). At 4 weeks of age, memory was assessed via a water maze test. To evaluate synaptic function, 2 specific synaptic proteins (postsynaptic density-95 [PSD95], synaptophysin) as well as insulin receptors (IR) were tested by Western Blot and quantitative polymerase chain reaction (qPCR). Brain-derived neurotrophic factor and serum insulin levels were also studied. RESULTS AND CONCLUSIONS: The RN+ group presented a learning curve similar to the NN animals. The RR animals without CUG showed learning disabilities. PSD95 was lower in the RR group than in the NN and RN+ mice. In contrast, synaptophysin was similar in all groups. IR showed an inverse expression pattern to that of the PSD95. In conclusion, perinatal nutrition plays an important role in learning. CUG after a period of prenatal malnutrition seems to improve learning skills. The functional alterations observed might be related to lower PSD95 activity and a possible dysfunction in the hormone regulation of synaptic plasticity.

Terapia prenatal con sulfato de magnesio: evolución clínica de los recién nacidos pretérmino menores de 29 semanas y correlación con la magnesemia neonatal / Prenatal treatment with magnesium sulphate: initial clinical outcomes in pre-term infants less than 29 weeks and correlation with neonatal magnesium levels

INTRODUCCIÓN: La administración prenatal de MgSO4ha mostrado su eficacia en reducir la parálisis cerebral y la disfunción motora severa a los 2 años de edad. El objetivo de este trabajo es estudiar la evolución clínica inicial de los neonatos menores de 29 semanas, que han recibido prenatalmente MgS04 con indicación neuroprotectora y dilucidar la asociación entre la dosis de magnesio administrada a la madre y las concentraciones de magnesio en suero neonatal. MATERIAL Y MÉTODOS: Estudio prospectivo de cohortes en el que se incluyó a los neonatos menores de 29 semanas ingresados en la Unidad de Cuidados Intensivos Neonatales del Hospital Universitario de Vigo desde diciembre del 2012 hasta julio del 2015. Análisis comparativo de resultados perinatales, de morbimortalidad neonatal y magnesemia entre el grupo expuesto prenatalmente al sulfato de magnesio y un grupo control. RESULTADOS: Se incluyó a un total de 42 recién nacidos, en 28 de los cuales sus madres habían recibido MgSO4. Se encontró significación estadística en la variable mortalidad. No hubo diferencias significativas en el resto de las variables estudiadas. Se obtuvo una correlación significativa entre la dosis total de MgSO4 recibida por la madre y los niveles de magnesio del recién nacido en las primeras 24 h de vida (r2 0,436; p < 0,001). CONCLUSIONES: Se ha obtenido una menor mortalidad en el grupo expuesto a MgS04. No se han encontrado efectos secundarios significativos derivados de la administración de MgS04. La dosis de MgSO4 recibida por las madres tiene una relación lineal con los niveles de magnesio obtenidos en los recién nacidos

INTRODUCTION: Antenatal magnesium sulphate (MgSO4) administration has shown to be effective in minimising cerebral palsy and severe motor dysfunction at the age of 2 years. The aim of this study is to analyse the initial clinical outcome of preterm neonates less than 29 weeks who have received prenatal MgSO4, as well as to determine the relationship between the magnesium dose delivered to the mother and the magnesium concentration in the neonates. MATERIAL AND METHODS: A prospective cohort study was conducted on neonates of less than 29 weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) of Hospital Universitario de Vigo from December 2012 to July 2015. Comparative analysis was performed on the perinatal outcomes, neonatal morbidity, mortality, and magnesium levels between the groups of neonates exposed to magnesium sulphate and the control group. RESULTS: A total of 42 neonates were included in the study. The mothers of 28 of them had received MgSO4 as a neuroprotective agent. Statistical significance was obtained in the mortality variable. There were no significant differences in the rest of studied variables. There was a significant correlation between the full dose of MgSO4 received by the mother and the levels of magnesium in the neonate in the first 24hours of life (r2 0.436; P<.001). CONCLUSIONS: A lower mortality was observed in the group that had been exposed to MgS04. No significant side effects were found as a result of administering of MgS04. The MgS04 dose received by mother has a linear relationship with the magnesium levels obtained in neonates

[Prenatal treatment with magnesium sulphate: Initial clinical outcomes in pre-term infants less than 29 weeks and correlation with neonatal magnesium levels]. / Terapia prenatal con sulfato de magnesio: evolución clínica de los recién nacidos pretérmino menores de 29 semanas y correlación con la magnesemia neonatal.

INTRODUCTION: Antenatal magnesium sulphate (MgSO4) administration has shown to be effective in minimising cerebral palsy and severe motor dysfunction at the age of 2 years. The aim of this study is to analyse the initial clinical outcome of preterm neonates less than 29 weeks who have received prenatal MgSO4, as well as to determine the relationship between the magnesium dose delivered to the mother and the magnesium concentration in the neonates. MATERIAL AND METHODS: A prospective cohort study was conducted on neonates of less than 29 weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) of Hospital Universitario de Vigo from December 2012 to July 2015. Comparative analysis was performed on the perinatal outcomes, neonatal morbidity, mortality, and magnesium levels between the groups of neonates exposed to magnesium sulphate and the control group. RESULTS: A total of 42 neonates were included in the study. The mothers of 28 of them had received MgSO4 as a neuroprotective agent. Statistical significance was obtained in the mortality variable. There were no significant differences in the rest of studied variables. There was a significant correlation between the full dose of MgSO4 received by the mother and the levels of magnesium in the neonate in the first 24hours of life (r2 0.436; P<.001). CONCLUSIONS: A lower mortality was observed in the group that had been exposed to MgS04. No significant side effects were found as a result of administering of MgS04. The MgS04 dose received by mother has a linear relationship with the magnesium levels obtained in neonates.