40 years neonatology : An academic life.

Background: A complete review of the development of neonatology in the last 40 years would probably require a compendium with several volumes, to bring to view the remarkable improvements in survival rates and neurodevelopmental outcomes of ill babies in Austria, most industrial countries and to some extent worldwide. The challenge I had to solve here was to integrate my own contributions to the field of neonatology during this period and particularly the contributions of my team from the Division of Neonatology and Pediatric Intensive Care Medicine, Department of Pediatrics and Adolescence Medicine, Medical University Vienna where I was working first as an intern and resident and later had the privilege to become head of department.

Aim: This very personal review was conceived to showcase the milestones of neonatology where, in my opinion, our department made some meaningful contributions in research and clinical practice during the past 40 years.

Early-life iron deficiency persistently disrupts affective behaviour in mice.

Background/objective: Iron deficiency (ID) is the most common nutrient deficiency, affecting two billion people worldwide, including about 30% of pregnant women. During gestation, the brain is particularly vulnerable to environmental insults, which can irrevocably impair critical developmental processes. Consequently, detrimental consequences of early-life ID for offspring brain structure and function have been described.

Maternal immune activation during pregnancy impacts on brain structure and function in the adult offspring.

Gestational infection constitutes a risk factor for the occurrence of psychiatric disorders in the offspring. Activation of the maternal immune system (MIA) with subsequent impact on the development of the fetal brain is considered to form the neurobiological basis for aberrant neural wiring and the psychiatric manifestations later in offspring life. The examination of validated animal models constitutes a premier resource for the investigation of the neural underpinnings.

Maternal immune activation transgenerationally modulates maternal care and offspring depression-like behavior.

Gestational infection is increasingly being recognized for its involvement as causative mechanism in severe developmental brain abnormalities and its contribution to the pathogenesis of psychopathologies later in life. First observations in the widely accepted maternal immune activation (MIA) model based upon the systemic administration of the viral mimetic Polyinosinic:polycytidylic acid (poly(I:C)) have recently suggested a transmission of behavioral and transcriptional traits across generations. Although maternal care behavior (MCB) is known as essential mediator of the transgenerational effects of environmental challenges on offspring brain function and behavior, the possible propagation of alterations of MCB resulting from MIA to following generations has not yet been examined.

GM-CSF Down-Regulates TLR Expression via the Transcription Factor PU.1 in Human Monocytes.

Toll-like receptors (TLR) are crucial sensors of microbial agents such as bacterial or viral compounds. These receptors constitute key players in the induction of inflammation, e.g.

Reduced cortical neurotransmitter receptor complex levels in fetal Down syndrome brain.

In this study, cortical receptor complex levels were determined in fetal Down syndrome (DS, trisomy 21) brain. Frontal cortices were obtained from individuals with DS (19th-22nd week of gestation) and controls. Membrane proteins were extracted, assayed on blue native gels and immunoblotted with brain receptor antibodies.

A cluster of protein kinases and phosphatases modulated in fetal Down syndrome (trisomy 21) brain.

Down syndrome (DS; trisomy 21) is the most frequent cause of mental retardation with major cognitive and behavioral deficits. Although a series of aberrant biochemical pathways has been reported, work on signaling proteins is limited. It was, therefore, the aim of the study to test a selection of protein kinases and phosphatases known to be essential for memory and learning mechanisms in fetal DS brain.

Hippocampal receptor complexes paralleling LTP reinforcement in the spatial memory holeboard test in the rat.

The current study was designed to examine learning-induced transformation of early-LTP into late-LTP. Recording electrodes were implanted into the dentate gyrus of the hippocampus in male rats and early-LTP was induced by weak tetanic stimulation of the medial perforant path. Dorsal right hippocampi were removed, membrane proteins were extracted, separated by blue-native gel electrophoresis with subsequent immunoblotting using brain receptor antibodies.

The poly(I:C)-induced maternal immune activation model in preclinical neuropsychiatric drug discovery.

Increasing epidemiological and experimental evidence implicates gestational infections as one important factor involved in the pathogenesis of several neuropsychiatric disorders. Corresponding preclinical model systems based upon maternal immune activation (MIA) by treatment of the pregnant female have been developed. These MIA animal model systems have been successfully used in basic and translational research approaches, contributing to the investigation of the underlying pathophysiological mechanisms at the molecular, cellular and behavioral levels.

Bispectral index and lower margin amplitude of the amplitude-integrated electroencephalogram in neonates.

Background: The lower margin amplitude (LMA) of the amplitude-integrated electroencephalogram (aEEG) is suppressed in neonates during deep sedation, a feature that is attributed to the bispectral index (BIS) in adults.

Objective: We compare the BIS and the LMA of the aEEG in neonates.

Methods: Thirty neurologically healthy neonates between 37 and 44 weeks postmenstrual age were included in this study.

The Austrian Toxoplasmosis Register, 1992-2008.

Background: We aimed to determine the incidence of primary gestational infections with Toxoplasma gondii and congenital toxoplasmosis in Austria, a country with a nationwide prenatal serological screening program since 1974.

Methods: We analyzed retrospective data from the Austrian Toxoplasmosis Register of pregnant women with Toxoplasma infection and their offspring with births between 1992 and 2008, identified by the prenatal mandatory screening program. Treatment was administered to women from diagnosis of a Toxoplasma infection until delivery.

Protein kinases paralleling late-phase LTP formation in dorsal hippocampus in the rat.

Hippocampal long term potentiation (LTP), representing a cellular model for learning and memory formation, can be dissociated into at least two phases: a protein-synthesis-independent early phase, lasting about 4h and a protein-synthesis-dependent late phase LTP lasting 6h or longer, or even days. A large series of protein kinases have been shown to be involved and herein, a distinct set of protein kinases proposed to be involved in memory retrieval in previous work was tested in dorsal hippocampus of the rat following induction of late-phase LTP. A bipolar stimulation electrode was chronically implanted into the perforant path, while two monopolar recording electrodes were implanted into the dentate gyrus of the dorsal hippocampus.

Hippocampal proteoglycans brevican and versican are linked to spatial memory of Sprague-Dawley rats in the morris water maze.

Proteoglycans (PGs) are major constituents of the extracellular matrix and have recently been proposed to contribute to synaptic plasticity. Hippocampal PGs have not yet been studied or linked to memory. The aim of the study, therefore, was to isolate and characterize rat hippocampal PGs and determine their possible role in spatial memory.

A hippocampal nicotinic acetylcholine alpha 7-containing receptor complex is linked to memory retrieval in the multiple-T-maze in C57BL/6j mice.

The link between the cholinergic and serotonergic system in cognitive function is well-documented. There is, however, limited information on spatial memory and this formed the rationale to carry out a study with the aim to show a specific link between nicotinic and serotonergic receptor complexes rather than the corresponding subunits, to spatial memory retrieval in a land maze. A total of 46 mice were used and divided into two groups, trained and untrained (yoked) in the multiple-T-Maze (MTM) and following training during the first four days, probe trials for memory retrieval were performed on days 8, 16 and 30.

The differential hippocampal phosphoproteome of Apodemus sylvaticus paralleling spatial memory retrieval in the Barnes maze.

Protein phosphorylation is a well-known and well-documented mechanism in memory processes. Although a large series of protein kinases involved in memory processes have been reported, information on phosphoproteins is limited. It was therefore the aim of the study to determine a partial and differential phosphoproteome along with the corresponding network in hippocampus of a wild caught mouse strain with excellent performance in several paradigms of spatial memory.

Austrian Newborn Screening Program: a perspective of five decades.

In 1966, the National Austrian Newborn Screening Program for inherited metabolic and endocrine disorders was initiated. In the last five decades, around four million babies were screened and in more than 2600 babies, various inborn errors of metabolism and endocrine disorders were detected. This health-preventive program was continuously expanded from phenylketonuria and galactosemia to congenital hypothyroidism, biotinidase deficiency, cystic fibrosis, and congenital adrenal hyperplasia.

Hippocampal protein kinase C family members in spatial memory retrieval in the mouse.

Although a few individual members of the protein kinase C (PKC) family were studied in spatial memory no systematic approach was carried out to concomitantly determine all described PKC family members in spatial memory of the mouse. It was therefore the aim of the current study to link hippocampal PKCs to memory retrieval in the Morris water maze (MWM). CD1 mice were trained (n=9) or untrained (n=9) in the MWM, hippocampi were taken 6h following the test for memory retrieval and PKCs were determined in mouse hippocampi by immunoblotting.

Influence of mask type and mask position on the effectiveness of bag-mask ventilation in a neonatal manikin.

Unlabelled: Anatomical face mask with an air cushion rim might be placed accidentally in a false orientation on the newborn's face or filled with various amounts of air during neonatal resuscitation. Both false orientation as well as variable filling may reduce a tight seal and therefore hamper effective positive pressure ventilation (PPV). We aimed to measure the influence of mask type and mask position on the effectiveness of PPV.

The early prediction of neonatal morbidity and mortality in singleton small for gestational age infants with a birthweight < 1,500 g.

Objective: Identify factors for discrimination of "high" and "low risk" small for gestational age infants.

Study Design: Singleton infants born small for gestational age with a birthweight  <1,500 g between 1999 and 2007 were included. Maternal, placental, and infant related factors were analyzed with regard to mortality and morbidity.

Behavioral effects of alpha-alkylated amino acid analogs in the C57BL/6J mouse.

Although a series of amino acid analogs have been shown to modulate brain function, information on the pharmacology of alpha-alkylated amino acids (AAAA) is limited. In particular there is no information on the effect of these amino acid analogs (AAA) on the elevated plus maze, the tail suspension test and the forced swim test. It was therefore the aim of the study to test a series of AAAA in these paradigms in order to explore behavioral activities of this compound class.

Successful implementation of a neonatal pain and sedation protocol at 2 NICUs.

Objective: To evaluate the implementation of a neonatal pain and sedation protocol at 2 ICUs.

Methods: The intervention started with the evaluation of local practice, problems, and staff satisfaction. We then developed and implemented the Vienna Protocol for Neonatal Pain and Sedation.

Two site evaluation of the performance of a new generation point-of-care glucose meter for use in a neonatal intensive care unit.

Background: Monitoring of blood glucose in neonatal intensive care unit (NICU) patients is important in maintaining normoglycaemia and reducing the risk of hypoglycaemia. Point-of-care testing (POCT) glucose meters provide short turnaround times but some have been reported to be affected by haematocrit interference and other biochemical or biological substances in their accuracy and performance. The aim of this study was to assess the performance of a new POCT glucose meter in a challenging preterm neonatal population.

Molecular detection of late-onset neonatal sepsis in premature infants using small blood volumes: proof-of-concept.

Background: Conventional blood culture is still the gold standard for sepsis diagnosis but results are not immediately available and pathogens are only detected in approximately 25% of cases. New molecular assays for the detection of blood stream pathogens are promising diagnostic tools.

Objectives: The aim of the study was to adapt and evaluate a multiplex PCR system using 100 µl blood.