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PURPOSE: Early adoption of a healthy lifestyle has positive effects on cardiovascular health (CVH) in adulthood. In this study, we aimed to assess CVH metrics in a cohort of healthy teenagers with focus on differences between rural and urban areas. METHODS: The Early Vascular Aging (EVA) Tyrol study is a population-based non-randomized controlled trial, which prospectively enrolled 14- to 19-year-old adolescents in North Tyrol, Austria and South Tyrol, Italy between 2015 and 2018. Data from the baseline and control group (prior to health intervention) are included in the current analysis. CVH determinants (smoking, body mass index, physical activity, dietary patterns, systolic and diastolic blood pressure, total cholesterol and fasting blood glucose) were assessed and analyzed for urban and rural subgroups separately by univariate testing. Significant variables were added in a generalized linear model adjusted for living in urban or rural area with age and sex as covariates. Ideal CVH is defined according to the guidelines of the American Heart Association. RESULTS: 2031 healthy adolescents were enrolled in the present study (56.2% female, mean age 16.5 years). 792 adolescents (39.0%) were from urban and 1239 (61.0%) from rural areas. In 1.3% of adolescents living in urban vs. 1.7% living in rural areas all CVH determinants were in an ideal range. Compared to the rural group, urban adolescents reported significantly longer periods of moderate to vigorous-intensive activity (median 50.0 min/day (interquartile range 30-80) vs. median 40.0 min/day (interquartile range 25-60), p < 0.01). This observation remained significant in a generalized linear model (p < 0.01). There were no significant differences between the study groups regarding all other CVH metrics. CONCLUSION: The low prevalence of ideal CVH for adolescents living in urban as well as rural areas highlights the need for early health intervention. Geographic differences must be taken into account when defining targeted subgroups for health intervention programs.
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Enfermedades Cardiovasculares/epidemiología , Estilo de Vida , Salud Rural , Salud Urbana , Adolescente , Factores de Edad , Austria/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & control , Dieta/efectos adversos , Dislipidemias/epidemiología , Ejercicio Físico , Femenino , Trastornos del Metabolismo de la Glucosa/epidemiología , Estado de Salud , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hipertensión/epidemiología , Italia/epidemiología , Masculino , Prevalencia , Estudios Prospectivos , Medición de Riesgo , Fumar/efectos adversos , Fumar/epidemiologíaRESUMEN
OBJECTIVES: We aimed to evaluate the ability of feed-forward neural networks (fNNs) to predict the neurodevelopmental outcome (NDO) of very preterm neonates (VPIs) at 12 months corrected age by using biomarkers of cerebral MR proton spectroscopy (1H-MRS) and diffusion tensor imaging (DTI) at term-equivalent age (TEA). METHODS: In this prospective study, 300 VPIs born before 32 gestational weeks received an MRI scan at TEA between September 2013 and December 2017. Due to missing or poor-quality spectroscopy data and missing neurodevelopmental tests, 173 VPIs were excluded. Data sets consisting of 103 and 115 VPIs were considered for prediction of motor and cognitive developmental delay, respectively. Five metabolite ratios and two DTI characteristics in six different areas of the brain were evaluated. A feature selection algorithm was developed for receiving a subset of characteristics prevalent for the VPIs with a developmental delay. Finally, the predictors were constructed employing multiple fNNs and fourfold cross-validation. RESULTS: By employing the constructed fNN predictors, we were able to predict cognitive delays of VPIs with 85.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 99.1% negative predictive value (NPV). For the prediction of motor delay, we achieved a sensitivity of 76.9%, a specificity of 98.9%, a PPV of 90.9% and an NPV of 96.7%. CONCLUSION: FNNs might be able to predict motor and cognitive development of VPIs at 12 months corrected age when employing biomarkers of cerebral 1H-MRS and DTI quantified at TEA. KEY POINTS: ⢠A feed-forward neuronal network is a promising tool for outcome prediction in premature infants. ⢠Cerebral proton magnetic resonance spectroscopy and diffusion tensor imaging can be used for the construction of early prognostic biomarkers. ⢠Premature infants that would most benefit from early intervention services can be spotted at the time of optimal neuroplasticity.
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Encéfalo/diagnóstico por imagen , Discapacidades del Desarrollo/diagnóstico , Imagen de Difusión Tensora/métodos , Interpretación de Imagen Asistida por Computador/métodos , Enfermedades del Prematuro/diagnóstico , Espectroscopía de Resonancia Magnética/métodos , Redes Neurales de la Computación , Encéfalo/fisiopatología , Discapacidades del Desarrollo/fisiopatología , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/fisiopatología , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Preterm-born children are at higher risk for impaired linguistic abilities than are their term-born peers. The aim of the current study was to determine early predictors for delayed linguistic skills in very preterm-born preschool children. METHODS: Between January 2005 and November 2010 all very preterm infants born atâ<â32 weeks gestation in Tyrol were prospectively enrolled (nâ=â421); 248 of them had a detailed examination at the age of five years including cognitive assessment (Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III) or Snijders-Oomen Nonverbal Intelligence Tests (SON-R)) as well as a screening test for language skills (Bielefelder screening for early diagnosis of reading problems and weak spelling (BISC)). The association between pre-and postnatal factors and poor performance on the BISC assessment was analyzed by means of logistic regression analysis. RESULTS: Of the 248 children 79 (31.8%) showed delayed literacy precursor skills. Male sex, gestational age, retinopathy of prematurity (ROP) grades 3-4 and low maternal education were predictive for delayed linguistic skills at 5 years of age in the multivariate analysis. CONCLUSION: This study identified predictors for delayed literacy precursor skills. These data support the finding that in very preterm infants pre-and perinatal as well as sociodemographic factors account for linguistic skills in the preschool period.
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Desarrollo Infantil/fisiología , Trastornos del Desarrollo del Lenguaje/etiología , Nacimiento Prematuro/fisiopatología , Austria/epidemiología , Niño , Femenino , Edad Gestacional , Humanos , Recién Nacido , Pruebas de Inteligencia , Trastornos del Desarrollo del Lenguaje/epidemiología , Trastornos del Desarrollo del Lenguaje/fisiopatología , Lingüística , Masculino , Valor Predictivo de las Pruebas , Nacimiento Prematuro/epidemiología , Estudios ProspectivosRESUMEN
AIM: The current study determined survival, short-term neonatal morbidity and predictors for death or adverse outcome of very preterm infants in Austria. METHODS: This population-based cohort study included 5197 very preterm infants (53.3% boys) born between 2011 and 2016 recruited from the Austrian Preterm Outcome Registry. Main outcome measures were gestational age-related mortality and major short-term morbidities. RESULTS: Overall, survival rate of all live-born infants included was 91.6% and ranged from 47.1% and 73.4% among those born at 23 and 24 weeks of gestation to 84.9% and 88.2% among infants born at 25 and 26 weeks to more than 90.0% among those with a gestational age of 27 weeks or more. The overall prevalence of chronic lung disease, necrotising enterocolitis requiring surgery, intraventricular haemorrhage Grades 3-4, and retinopathy of prematurity Grades 3-5 was 10.0%, 2.1%, 5.5%, and 3.6%, respectively. Low gestational age, low birth weight, missing or incomplete course of antenatal steroids, male sex, and multiple births were significant risk predictors for death or adverse short-term outcome. CONCLUSION: In this national cohort study, overall survival rates were high and short-term morbidity rate was low.
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Mortalidad Infantil , Recien Nacido Extremadamente Prematuro , Enfermedades del Prematuro/epidemiología , Austria/epidemiología , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
Fetal angiotensin II receptor antagonist exposure is associated with major complications and even death when administered during pregnancy. Neonates frequently require intensive care treatment, and mortality is high. Despite this well-known risk potential, a considerable number of women still receive angiotensin II receptor antagonists during pregnancy to treat arterial hypertension. Although clinical symptoms in the neonatal period are well described, few reports address long-term follow-up after fetal exposure to angiotensin II receptor antagonists. We here report on a patient who was unwittingly exposed to olmesartan medoxomil during pregnancy. After birth, the neonate presented with mild clinical symptoms, mainly affecting the kidneys. However, neurodevelopmental follow-up revealed a delay in motor development with muscular hypotonia and failure to thrive at age 2 years. This case highlights the fact that, despite not causing neurological symptoms in the neonatal period, fetal angiotensin II receptor antagonist exposure during pregnancy might lead to neurodevelopmental impairment in later life.
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Forkhead box O class transcription factors are homeostasis regulators that control cell death, longevity and therapy-resistance. In neuroblastoma (NB), nuclear FOXO3 correlates with stage M disease and poor prognosis. To analyze whether FOXO3 contributes to drug-resistance in this childhood cancer, we investigated how different high-stage-derived NB cells respond to the activation of an ectopic FOXO3 allele. We found endogenous FOXO3 mostly localized to the nucleus-upon activation of an ectopic, 4OHT-activated FOXO3(A3)ER fusion protein two of the cell lines underwent apoptosis, whereas in the others FOXO3-activation even increased survival during drug-treatment. In the latter cell type, FOXO3 did not induce the BH3-only protein BCL2L11/BIM due to impaired binding of FOXO3 to the BIM-promoter, but still activated other FOXO3 targets. It was shown before that FOXO3 and TP53 physically interact with each other at two different regions-the TP53-N-terminus binds to the FOXO3-DNA binding domain (DBD) and the FOXO3-C-terminus interacts with the TP53-DBD. Interestingly, cell lines that undergo FOXO3-induced cell death carry homozygous point mutations in the TP53-DBD near the structural hotspot-mutation-site R175H, which abrogated FOXO3-TP53 interaction. In contrast, in FOXO3-death-resistant cells no point mutations in the TP53-DBD were found-in these cells FOXO3-TP53 complexes are formed and FOXO3-binding to the BIM-promoter, but not the induction of the detoxifying protein SESN3, were prevented, which in turn increased chemo-protection in this type of high-stage-derived NB cells. Our combined data suggest that FOXO3 steps in as a death inducer in case of TP53-mutation, whereas functional TP53 alters FOXO3-target-promoter-recognition, which prevents death induction by FOXO3 and instead increases chemo-protection and survival of NB cells. This novel mechanism may explain the low incidence of TP53 mutation in high-stage NB at diagnosis and suggests FOXO3 as a therapeutic target for this childhood malignancy.
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Proteína 11 Similar a Bcl2/genética , Proteína Forkhead Box O3/genética , Proteínas de Choque Térmico/genética , Neuroblastoma/genética , Proteína p53 Supresora de Tumor/genética , Apoptosis/genética , Línea Celular Tumoral , Núcleo Celular/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Resistencia a Antineoplásicos/genética , Proteína Forkhead Box O3/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Mutación , Estadificación de Neoplasias , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/patología , Regiones Promotoras Genéticas , Unión Proteica , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
BACKGROUND: Neuroblastoma is the most common solid tumor in childhood and develops from undifferentiated progenitor cells of the sympathetic nervous system. In neuronal tumor cells DNA-damaging chemotherapeutic agents activate the transcription factor FOXO3 which regulates the formation of reactive oxygen species (ROS) and cell death as well as a longevity program associated with therapy resistance. We demonstrated before that C10ORF10/DEPP, a transcriptional target of FOXO3, localizes to peroxisomes and mitochondria and impairs cellular ROS detoxification. In the present study, we investigated the impact of FOXO3 and DEPP on the regulation of autophagy. Autophagy serves to reduce oxidative damage as it triggers a self-degradative process for the removal of aggregated or misfolded proteins and damaged organelles. METHODS: The effect of FOXO3 and DEPP on autophagy induction was analyzed using live cell fluorescence microscopy and immunoblot analyses of SH-EP cells transfected with a plasmid for EYFP-LC3 and with siRNAs specific for LC3, respectively. ROS steady-state levels were measured with reduced MitoTrackerRed CM-H2XROS. Cellular apoptosis was analyzed by flow cytometry and the caspase 3/7 assay. RESULTS: We report for the first time that DEPP induces ROS accumulation and thereby mediates the formation of autophagosomes as inhibition of ROS formation by N-acetyl-cysteine completely blocks autophagy. We further demonstrate that H2O2-treatment triggers autophagy-induction by FOXO3-mediated DEPP expression. Importantly, knockdown of DEPP was sufficient to efficiently inhibit autophagy-induction under different stress conditions such as serum starvation and genotoxic stress, suggesting that DEPP expression is critical for the initiation of autophagy in neuroblastoma. FOXO3-triggered autophagy partially protects neuroblastoma cells from cell death. Consistent with this concept, we demonstrate that inhibition of autophagy by LC3-knockdown significantly increased etoposide- and doxorubicin-induced apoptosis. These results were also confirmed by the use of the autophagy-inhibitor chloroquine that significantly enhanced the chemotherapeutic effect of etoposide and doxorubicin in neuronal tumor cells. CONCLUSION: Targeting FOXO3/DEPP-triggered autophagy is a promising strategy to sensitize neuroblastoma cells to chemotherapy.
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Autofagia/genética , Proteína Forkhead Box O3/genética , Proteínas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Doxorrubicina/farmacología , Etopósido/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteína Forkhead Box O3/metabolismo , Expresión Génica , Silenciador del Gen , Humanos , Péptidos y Proteínas de Señalización Intracelular , Modelos Biológicos , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patología , Fosforilación , Interferencia de ARN , ARN Interferente Pequeño/genética , Estrés FisiológicoRESUMEN
Adverse forms of neuroblastoma (NB), a childhood malignancy that develops from immature neuronal progenitor cells frequently carry a gain of chromosome 17q, which leads to overexpression of the antiapoptotic protein BIRC5/Survivin. We have recently shown that high Survivin expression shuts down mitochondrial complex I activity and shifts NB cells from oxidative phosphorylation to aerobic glycolysis, which further increases resistance to cell death induction. This increased glucose consumption sensitized tumor cells to glycolysis inhibitors. Interestingly, in Survivin-overexpressing cells 2-deoxy-d-glucose (2DG) treatment induces re-fusion of mitochondrial networks after 4 h, which coincides with Survivin repression. 2DG selectively acts on Survivin-expressing NB cells and induces autophagic degradation of Survivin via activation of the E3-ubiquitin ligase Parkin, a downstream target of PINK1. Survivin degradation further releases bound Beclin-1, which enhances autophagy and cell death induction. Knockdown of Parkin, however, reduces the sensitivity of Survivin-expressing NB cells to glycolysis inhibition. The selective activity of 2DG treatment on Survivin-overexpressing tumor cells was also confirmed in a xenograft mouse model, which further supports our hypothesis that glycolysis inhibitors might be useful drugs in the treatment of NB.
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Proteínas Inhibidoras de la Apoptosis/metabolismo , Neuroblastoma/metabolismo , Animales , Autofagia/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Desoxiglucosa/farmacología , Femenino , Glucólisis , Humanos , Ratones , Ratones Endogámicos BALB C , Neuroblastoma/patología , Fosforilación Oxidativa , Survivin , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
AIM: Being born small for gestational age (SGA) seems to be a relevant risk factor for long-term neurologic deficits. We compared the differences between amplitude-integrated electroencephalography (aEEG) signals in very preterm infants born small for gestational age (SGA) and those in age-matched infants born appropriate size for gestational age (AGA). METHODS: We performed serial aEEG recording on 305 infants: 255 (83.6%) were AGA, and 50 (16.3%) were SGA. RESULTS: The number of bursts per hour decreased over time in both groups, but was higher in the SGA group at every time point. On day one, it was significantly higher in the SGA group (17.4) than in the AGA group (10.1) (p = 0.016). The total Burdjalov score increased with post-natal age and tended to be lower in SGA infants, but did not reach statistical significance at any time point. The percentage of continuous background patterns increased with post-natal age in both groups, with no significant difference between the groups. CONCLUSION: Very preterm infants born SGA showed normal maturation of aEEG signals during post-natal life, but they also showed mild delays in electrocortical activity compared to age-matched AGA infants. The predictive value of these findings on neurodevelopmental outcome needs to be further evaluated.
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Corteza Cerebral/fisiología , Recién Nacido Pequeño para la Edad Gestacional/fisiología , Austria , Estudios de Casos y Controles , Electroencefalografía , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , MasculinoRESUMEN
Preterm infants are prematurely subjected to relatively high oxygen concentrations, even when supplemental oxygen is not administered. There is increasing evidence to show that an excess of oxygen is toxic to the developing brain. Dextromethorphan (DM), a frequently used antitussive agent with pleiotropic mechanisms of action, has been shown to be neuroprotective in various models of central nervous system pathology. Due to its numerous beneficial properties, it might also be able to counteract detrimental effects of a neonatal oxygen insult. The aim of the current study was to evaluate its therapeutic potential in established cell culture and rodent models of hyperoxia-induced neonatal brain injury. For in vitro studies pre- and immature oligodendroglial (OLN-93) cells were subjected to hyperoxic conditions for 48 h after pre-treatment with increasing doses of DM. For in vivo studies 6-day-old Wistar rat pups received a single intraperitoneal injection of DM in two different dosages prior to being exposed to hyperoxia for 24h. Cell viability and caspase-3 activation were assessed as outcome parameters at the end of exposure. DM significantly increased cell viability in immature oligodendroglial cells subjected to hyperoxia. In pre-oligodendroglial cells cell viability was not significantly affected by DM treatment. In vivo caspase-3 activation induced by hyperoxic exposure was significantly lower after administration of DM in gray and white matter areas. In control animals kept under normoxic conditions DM did not significantly influence caspase-3-dependent apoptosis. The present results indicate that DM is a promising and safe treatment strategy for neonatal hyperoxia-induced brain injury that merits further investigation.
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Apoptosis/efectos de los fármacos , Lesiones Encefálicas/tratamiento farmacológico , Dextrometorfano/farmacología , Hiperoxia/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Animales , Animales Recién Nacidos , Antitusígenos/farmacología , Apoptosis/fisiología , Encéfalo/efectos de los fármacos , Encéfalo/patología , Encéfalo/fisiopatología , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Caspasa 3/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Citocinas/toxicidad , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Sustancia Gris/efectos de los fármacos , Sustancia Gris/patología , Sustancia Gris/fisiopatología , Hiperoxia/patología , Hiperoxia/fisiopatología , Oligodendroglía/efectos de los fármacos , Oligodendroglía/patología , Oligodendroglía/fisiología , Oxígeno/metabolismo , Ratas Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores sigma/metabolismo , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/patología , Sustancia Blanca/fisiopatología , Receptor Sigma-1RESUMEN
A pneumothorax (PTX) is a potentially life threatening event during mechanical ventilation. Aim of this study was to analyse 3 different ways of management: expectant treatment, once-only pleural puncture and thoracic drainage.Retrospective data analysis in term and preterm neonates admitted to the NICU of the Medical University of Graz (between 2000-2010) and Innsbruck (2002-2010) who suffered from a PTX during continuous positive airway pressure (CPAP) or conventional mechanical ventilation (CMV).104 neonates, 33 term and 71 preterm neonates with PTX were included. 33 term neonates: 52% were treated expectantly, 36% with thoracic drainage and 12% with once-only pleural puncture (100% thoracic drainage after pleural puncture). 71 preterm neonates: 25% were treated expectantly, 52% with thoracic drainage and 23% with pleural puncture (63% thoracic drainage after pleural puncture). In CPAP-subgroup (n=64), term neonates were treated in 60% expectantly and in 40% with thoracic drain-age, preterm neonates in 33% expectantly, in 47% with thoracic drainage and in 20% with pleural puncture (50% thoracic drainage after pleural puncture). In CMV-subgroup (n=40), term neonates were treated in 44% expectantly, in 33% with thoracic drainage and in 22% with pleural puncture (100% thoracic drainage after pleural puncture), preterm neonates in 9% expectantly, in 64% with thoracic drainage and in 27% with pleural puncture (83% thoracic drain-age after pleural puncture).Present data show that expectant treatment is feasible. If invasive intervention is needed, once-only pleural puncture was not successful, as often thoracic drainage was necessary in addition.
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Enfermedades del Prematuro/terapia , Neumotórax/terapia , Respiración Artificial/efectos adversos , Austria , Tubos Torácicos , Presión de las Vías Aéreas Positiva Contínua , Drenaje , Estudios de Factibilidad , Femenino , Edad Gestacional , Humanos , Recién Nacido , Masculino , Estudios Retrospectivos , Factores de Riesgo , Espera VigilanteRESUMEN
Excessive glutamate release followed by N-methyl-D-aspartate receptor (NMDAR) activation plays a crucial role in perinatal brain injury. We have previously shown that dextromethorphan, a low-affinity NMDAR antagonist with anti-inflammatory properties, is neuroprotective against neonatal excitotoxic brain injury. Of interest, dextromethorphan is also a sigma-1 receptor (σ1R) agonist. The pharmacologic class of σ1R agonists has yielded propitious results in various animal models of adult central nervous system pathology. In an established neonatal mouse model of excitotoxic brain injury, we evaluated the effect of the selective σ1R agonist 2-(4-morpholinethyl) 1-phenylcyclohexanecarboxylate (PRE-084). A single intraperitoneal injection of 0.1 µg/g (low dose) or 10 µg/g (high dose) bodyweight (bw) PRE-084, given 1h after the excitotoxic insult, significantly reduced lesion size in cortical gray matter 24 h and 120 h after the insult. Repetitive injections of 0.1 µg/g PRE-084 proved to be equally effective. PRE-084 treatment resulted in a decrease in cell death indicated by reduced TUNEL positivity and caspase-3 activation. Furthermore, it lowered the number of isolectin B4-positive, activated microglial cells. PRE-084 had no effect on developmental apoptosis in the undamaged brain. In vitro findings in primary hippocampal neurons suggest that PRE-084 treatment provides partial protection against glutamate induced morphological and functional changes. For excitotoxicity as playing a crucial role in the pathogenesis of perinatal brain injury, we demonstrate for the first time that systemic treatment with the highly selective σ1R agonist PRE-084 protects against NMDAR-mediated excitotoxic brain damage.
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Lesiones Encefálicas/tratamiento farmacológico , Morfolinas/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Lesiones Encefálicas/inducido químicamente , Lesiones Encefálicas/patología , Aminoácidos Excitadores/toxicidad , Ácido Glutámico/toxicidad , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Ligandos , Ratones , Microscopía Confocal , Neuronas/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores sigma/agonistas , Receptor Sigma-1RESUMEN
AIM: MRI is gaining in importance as an imaging tool for brain development and injury in preterm infants. The aim of this study was to evaluate the feasibility of performing MRI in non-sedated preterm-born infants at term-equivalent age (TEA). METHODS: A total of 89 infants born before 32 gestational weeks were recruited. Infants were scanned without sedation. Duration of the entire examination including scan repetition and interruptions was registered. RESULTS: Of the 89 infants, 56 (63%) underwent MRI at TEA. Out-patients required a significantly shorter total MR examination time than did in-patients (32 ± 12 vs. 54 ± 10 min, p < 0.01). Of the 56 infants, 39 (69.6%) were examined without interruption. Only four (7.2%) of the 56 scans were unusable because of motion artefacts. Mean duration of all scans was 36 ± 14 min. In cases with no interruptions, sessions were completed within 32 ± 12 min; MR sessions with interruption lasted 45 ± 13 min. CONCLUSION: A well-trained team is indispensable in obtaining best-quality images as a prerequisite for good counselling. From our experience, we worked out a guideline to ensure that scans in stable non-sedated preterm-born infants at TEA run smoothly and provide high-quality images.
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Lesiones Encefálicas/diagnóstico , Encéfalo/crecimiento & desarrollo , Recien Nacido Prematuro/fisiología , Imagen por Resonancia Magnética/métodos , Austria , Encéfalo/patología , Lesiones Encefálicas/patología , Diagnóstico por Imagen/métodos , Estudios de Factibilidad , Femenino , Edad Gestacional , Humanos , Recién Nacido , Pacientes Internos , Imagen por Resonancia Magnética/normas , Masculino , Servicio Ambulatorio en Hospital , Proyectos Piloto , Estudios Prospectivos , Factores de TiempoRESUMEN
Hypoxia-ischaemia (HI) is a major factor in the pathogenesis of developmental brain injury, leading to cognitive deficits and motor disabilities in preterm infants. The haematopoietic growth factor granulocyte colony-stimulating factor (G-CSF) has been shown to exert a neuroprotective activity in rodent models of ischaemic stroke and is currently subject to phase I/II clinical trials in adults. Results of studies examining the effect of G-CSF in perinatal brain damage have been contradictory. We have previously shown that G-CSF increases NMDAR-mediated excitotoxic brain injury in the neonatal mouse brain. In this study, we evaluated the effect of G-CSF on long-term outcomes after HI. On postnatal day 5, mice pubs were first randomly assigned to a sham operation or HI and then divided into four treatment groups: i) G-CSF; ii) phosphate buffered saline (PBS) 1h after injury; iii) G-CSF and iv) PBS 60 h after injury. G-CSF (200 µg/kg BW) was administered five times within a 24h interval. Neuromotor and cognitive outcomes were assessed by open-field, novel object recognition tests and rotarod tests starting on P90, with subsequent histological analyses of brain injury. G-CSF treatment did not improve either neurobehavioural outcomes or brain injuries. Interestingly, the application of PBS and G-CSF in the acute phase increased brain damage in the hippocampus. We could not confirm the neuroprotective properties of G-CSF in neonatal HI brain damage. The exacerbation of injury by the administration of substances in the acute phase might indicate a heightened state of neurological sensitivity that is specific to mechanisms of secondary neurodegeneration and influenced by unidentified external factors possibly associated with the treatment protocol during the acute phase. This article is part of a Special Issue entitled "Interaction between repair, disease, & inflammation."
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Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Factores de Edad , Animales , Animales Recién Nacidos , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/etiología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Modelos Animales de Enfermedad , Conducta Exploratoria/efectos de los fármacos , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/patología , Ratones , Ratones Endogámicos ICR , Actividad Motora/efectos de los fármacos , ARN Mensajero/metabolismo , Receptores de Factor Estimulante de Colonias de Granulocito/genética , Receptores de Factor Estimulante de Colonias de Granulocito/metabolismo , Reconocimiento en Psicología/efectos de los fármacos , Prueba de Desempeño de Rotación con Aceleración Constante , Factores de TiempoRESUMEN
Twin-to-twin transfusion syndrome and conital cytomegalovirus infection bear the risk of brain damage. In the 27th week of gestation of a twin pregnancy a Caesarean section was performed because of pathological cardiotocogram and Doppler ultrasonography of the second twin (recipient). Both infants presented with severe, persistent thrombocytopenia, elevated liver enzymes and direct hyperbilirubinemia. Primary congenital CMV infection was diagnosed. Both twins showed severe neuropathological symptoms, pathological aEEG with seizure activity and severe neurodevelopmental delay at corrected age of 12 months. The severity of brain pathology, the complex etiology, its consequence for neurotion with extreme prematurity make this case of special interest.
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Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/diagnóstico , Discapacidades del Desarrollo/diagnóstico , Enfermedades en Gemelos/diagnóstico , Transfusión Feto-Fetal/diagnóstico , Enfermedades del Prematuro/diagnóstico , Daño Encefálico Crónico/diagnóstico , Quistes del Sistema Nervioso Central/diagnóstico , Ecoencefalografía , Femenino , Estudios de Seguimiento , Gastrosquisis/diagnóstico , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Reacción en Cadena de la Polimerasa , Embarazo , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico , Retinopatía de la Prematuridad/diagnóstico , Espasmos Infantiles/diagnósticoRESUMEN
AIM: To assess whether smoking in pregnancy influences neurodevelopmental outcome at 2-years of age in preterm infants with a gestational age <32 weeks. METHODS: Between January 2003 and December 2005 we prospectively enrolled 181 infants born alive between 23 and 32 weeks of gestation; 142 infants (78.5%) completed the follow-up visit. The association between candidate risk factors and delayed motor or mental development (Bayley Scales of Infant Development II; psychomotor or mental developmental index <85) was analysed by means of logistic regression analysis. RESULTS: Low maternal age, smoking in pregnancy, low gestational age, low birth weight, small for gestational age, chronic lung disease, intracerebral haemorrhage, periventricular leucomalacia, and retinopathy of prematurity (stages 3 and 4) all were associated with an increased risk for delayed development (p < 0.05, each). Smoking in pregnancy, small for gestational age and chronic lung disease maintained significance in a multivariable analysis. CONCLUSION: Smoking in pregnancy emerged as a risk predictor for adverse neurodevelopmental outcome in our study. Strategies to reduce smoking in pregnancy should be further endorsed.
Asunto(s)
Discapacidades del Desarrollo/etiología , Enfermedades del Prematuro/etiología , Efectos Tardíos de la Exposición Prenatal , Fumar/efectos adversos , Adulto , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Recien Nacido Prematuro , Recién Nacido Pequeño para la Edad Gestacional , Modelos Logísticos , Lesión Pulmonar , Masculino , Análisis Multivariante , Embarazo , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
AIM: Assessment of risk predictors for adverse neurodevelopmental outcome at 1 year of age in preterm infants with a gestational age <30 weeks (Group I) and 30-32 weeks (Group II). METHODS: Between January 2003 and December 2006, we prospectively enrolled 310 live-born infants between 23 and 32 weeks of gestation. The association between candidate risk factors and delayed motor or mental development (Bayley Scales of infant development II; psychomotor or mental developmental index <85) was analysed by means of logistic regression analysis. RESULTS: Two hundred and fifty infants were eligible for follow-up, and 205 (82.0%) completed the follow-up visit. Intracerebral haemorrhage, small for gestational age and late-onset sepsis were associated with an increased risk for delayed development in Group I (p < 0.05, each). Premature rupture of membranes was a risk condition relevant to Group II. Antenatal steroids were associated with a decreased risk of neurodevelopmental delay in both groups. CONCLUSION: This study identified distinct risk factors for adverse outcome in preterm infants of lower (<30 weeks) and higher (30-32 weeks) gestational age. In the lower gestational age group, neonatal risk predictors are most important. Antenatal steroids appear to decrease the risk for adverse outcome in both age groups.
Asunto(s)
Discapacidades del Desarrollo/epidemiología , Edad Gestacional , Enfermedades del Prematuro/epidemiología , Enfermedades del Sistema Nervioso/epidemiología , Austria/epidemiología , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: A prospective study to evaluate long-term pregnancy outcome and childhood development of chromosomally normal foetuses with increased nuchal translucency thickness (NT) at 10-14 weeks of gestation. METHODS: Between Jan 1, 1997 and Dec 31, 2001 78 foetuses with increased NT but normal karyo-type were identified from the database of the Department of Obstetrics and Gynaecology at Innsbruck Medical University. To evaluate long term cognitive abilities and social skills standardized questionnaires ("Elternfragebogen zur ergänzenden Entwicklungsbeurteilung bei den kinderärztlichen Vorsorgeuntersuchungen U6 bis U9"EEE U6-U9; "Kognitive Probleme bei Kindern und Jugendlichen--Vorstellung eines Fragebogens" KOPKIJ) were used. 41 children with increased nuchal translucency were compared with 41 control children matched for date of birth, gestational and maternal age. RESULTS: Follow-up data could be collected in 44 cases. 2 out of 78 foetuses died intrauterine, one infant died after birth. Two out of the 41 surviving infants showed genetic disorders. There was no significant difference in cognitive delay between children with increased NT and controls (9.8% vs. 2.4%, p=0.361). CONCLUSION: Our findings suggest that chromosomally normal foetuses with increased nuchal translucency in the first-trimester scan do not have an increased risk for a significant cognitive developmental delay in an observation period of up to six years.
Asunto(s)
Cognición , Medida de Translucencia Nucal , Resultado del Embarazo , Preescolar , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Lactante , Cariotipificación , Masculino , Edad Materna , Embarazo , Estudios Prospectivos , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
UNLABELLED: Our aim was to review the risk of sudden infant death syndrome (SIDS) when infants are in child care (CC), to discuss factors potentially responsible for SIDS in this setting and to describe the impact of previous information campaigns on SIDS in CC. There is a remarkably increased risk of SIDS in CC settings. Special education focussing on a safe sleeping environment has resulted in a decrease of practices known to be associated with SIDS. However, despite a safe sleep environment SIDS prevalence remains disproportionately high. CONCLUSION: Efforts must continue to ensure safe sleeping practices in CC facilities. The possibility of other explanations for the increased prevalence of SIDS in CC settings, such as changes in infant care or stress, must be considered as well.
Asunto(s)
Guarderías Infantiles , Cuidado del Lactante , Muerte Súbita del Lactante/epidemiología , Humanos , Lactante , Factores de Riesgo , Muerte Súbita del Lactante/etiología , Posición SupinaRESUMEN
BACKGROUND: Asthma is among the most common chronic diseases in childhood and is steadily increasing in prevalence. Better characterisation of factors that determine the risk of hospitalisation for atopic asthma in childhood may help design prevention programmes and improve our understanding of disease pathobiology. This study will focus on the altitude of residence. METHODS: This is an ongoing prospective birth-cohort study that enrolled all live-born infants in the Tyrol. Between 1994 and 1999, baseline data were collected for 33 808 infants. From 2000 to 2005, all children hospitalised for atopic asthma at the age of > or =6 years (n = 305) were identified by a careful search of hospital databases. Disease status was ascertained from the typical medical history, a thorough examination and proof of atopy. RESULTS: Living at higher altitude was associated with an enhanced risk of hospitalisation for atopic asthma (multivariate RRs (95% confidence interval 2.08 (1.45 to 2.98) and 1.49 (1.05 to 2.11) for a comparison between altitude categories > or =1200 m and 900-1199 m versus <900 m; p<0.001). This finding applied equally to hospital admissions in spring, summer, autumn and winter. When altitude of residence was analysed as a continuous variable, the risk for asthma hospitalisation increased by 7% for each 100-m increase in altitude (p = 0.013). CONCLUSIONS: This large prospective study shows a significant association between the risk of hospitalisation for atopic asthma and altitude of residence between 450 and 1800 m. The underlying mechanisms remain to be elucidated, but it is tempting to speculate about a role for altitude characteristics such as the decline in outdoor temperature and air humidity and increase in ozone levels, which may trigger airway hyper-responsiveness and attenuate lung function.