Evaluation of the effect of chance correlations on variable selection using Partial Least Squares -Discriminant Analysis

Variable subset selection is often mandatory in high throughput metabolomics and proteomics. However, depending on the variable to sample ratio there is a significant susceptibility of variable selection towards chance correlations. The evaluation of the predictive capabilities of PLSDA models estimated by cross-validation after feature selection provides overly optimistic results if the selection is performed on the entire set and no external validation set is available. In this work, a simulation of the statistical null hypothesis is proposed to test whether the discrimination capability of a PLSDA model after variable selection estimated by cross-validation is statistically higher than t…

Consequences of neonatal resuscitation with supplemental oxygen.

There has been considerable controversy surrounding the optimal inspired oxygen concentration for resuscitation of term and preterm infants. We have developed a rat pup model to quantify both physiologic and biochemical parameters associated with normoxic vs. hyperoxic resuscitation. We have confirmed existing human data that hyperoxic resuscitation of rat pups is associated with a significant delay in onset of spontaneous respiratory efforts. Both 40% and 100% inspired oxygen delayed onset of respiratory activity when compared to 21% oxygen. We have also documented, in the rat pup model, that hyperoxic resuscitation is associated with reduced levels of glutathione at 24 hours post resuscit…

Biomonitoring of non-persistent pesticides in urine from lactating mothers: Exposure and risk assessment

Abstract The aim of the present study was to assess the exposure to pesticides in urine from Spanish lactating mothers (n = 116). Six nonspecific (dialkyl phosphates) and 20 specific metabolites of organophosphate pesticides (OPs), herbicides and pyrethroids were analyzed. The most frequently detected biomarkers were diethyl phosphate, p-nitrophenol, 3,5,6-trichloro-2-pyridinol and 3-phenoxybenzoic acid, whose geometric means were 1.9 ng·mL−1, 0.8 ng·mL−1, 1.5 ng·mL−1 and 1.4 ng·mL−1, respectively. Herbicide metabolites were the least frequently detected biomarkers with detection frequencies between 0% (2,4,5-Trichlorophenoxyacetic acid) and 22% (2,4-Dichlorophenoxyacetic acid). Multiple re…

Estudio de los mecanismos fisiopatológicos asociados al inicio y curso de los trastornos del neurodesarrollo en prematuros (estudio PeriSTRESS-PremTEA): justificación, objetivos, diseño y descripción de la muestra

Resumen Introduccion Los factores genetico-ambientales y las vias fisiopatologicas que condicionan la evolucion de forma diferencial a un trastorno de neurodesarrollo (TN) en la poblacion de grandes prematuros (GP) y prematuros extremos (PE) siguen siendo en gran medida desconocidos. Tampoco disponemos a fecha de hoy de marcadores biologicos potencialmente predictivos de TN en estos ninos. El proyecto PeriSTRESS-PremTEA tiene como objetivo estudiar de forma prospectiva, en GP/PE: (i) la aparicion/curso de rasgos y diagnostico TN hasta los 6 anos de vida, (ii) factores de riesgo de aparicion de TN desde la etapa prenatal hasta los 6 anos, (ii) perfiles de biomarcadores en orina predictivos d…

28 Milrinone is Preferred to Levosimendan for Mesenteric Perfusion in Hypoxia-Reoxygenated Newborn Piglets on Dopamine

28 Milrinone is Preferred to Levosimendan for Mesenteric Perfusion in Hypoxia-Reoxygenated Newborn Piglets on Dopamine

Biomonitoring of polycyclic aromatic hydrocarbons in the urine of lactating mothers: Urinary levels, association with lifestyle factors, and risk assessment

Abstract Polycyclic aromatic hydrocarbons (PAHs) are pollutants produced during incomplete combustion of organic matter and several industrial processes. Humans can be exposed to PAHs through ingestion of food, inhalation of tobacco smoke or polluted air, and dermal contact, causing immunologic, developmental, and reproductive problems. In the present research, eleven metabolites of PAHs were analyzed in the urine of 110 lactating women living in Spain (2015). PAH metabolites were extracted from the urine samples by liquid-liquid extraction and their determination was performed by liquid chromatography coupled to tandem mass spectrometry. In addition, information on lifestyle and dietary ha…

Trajectories of stress biomarkers and anxious-depressive symptoms from pregnancy to postpartum period in women with a trauma history

Background: Cross-sectional studies have found that a trauma history can be associated with anxious-depressive symptomatology and physiological stress dysregulation in pregnant women. Methods: This prospective study examines the trajectories of both anxiety and depressive symptoms and salivary cortisol and alpha-amylase biomarkers from women with (n = 42) and without (n = 59) a trauma history at (i) 38th week of gestation (T1), (ii) 48 hours after birth (T2), and (iii) three months after birth (T3). Results: The quantile regression model showed that trauma history was associated with higher cortisol levels at T1 and this difference was sustained along T2 and T3. Conversely, there were no si…

Human milk enhances antioxidant defenses against hydroxyl radical aggression in preterm infants

Background: Preterm infants endowed with an immature antioxidant defense system are prone to oxidative stress. Hydroxyl radicals are very aggressive reactive oxygen species that lack specific antioxidants. These radicals cannot be measured directly, but oxidation byproducts of DNA or phenylalanine in urine are reliable markers of their activity. Human milk has a higher antioxidant capacity than formula. Objective: We hypothesized that oxidative stress associated with prematurity could be diminished by feeding human milk. Design: We recruited a cohort of stable preterm infants who lacked perinatal conditions associated with oxidative stress; were not receiving prooxidant or antioxidant drugs…

Oxygen in the neonatal period: Oxidative stress, oxygen load and epigenetic changes

Preterm infants frequently require positive pressure ventilation and oxygen supplementation in the first minutes after birth. It has been shown that the amount of oxygen provided during stabilization, the oxygen load, if excessive may cause hyperoxia, and oxidative damage to DNA. Epidemiologic studies have associated supplementation with pure oxygen in the first minutes after birth with childhood cancer. Recent studies have shown that the amount of oxygen supplemented to preterm infants after birth modifies the epigenome. Of note, the degree of DNA hyper-or hypomethylation correlates with the oxygen load provided upon stabilization. If these epigenetic modifications would persist, oxygen su…

Validation of the Sepsis MetaScore for Diagnosis of Neonatal Sepsis

What’s known on this subject Neonates are at increased risk for developing sepsis, but this population often exhibits ambiguous clinical signs that complicate the diagnosis of infection. No biomarker has yet shown enough diagnostic accuracy to rule out sepsis at the time of clinical suspicion. What this study adds We show that a gene-expression-based signature is an accurate objective measure of the risk of sepsis in a neonate or preterm infant, and it substantially improves diagnostic accuracy over that of commonly used laboratory-based testing. Implementation might decrease inappropriate antibiotic use. Background Neonatal sepsis can have devastating consequences, but accurate diagnosis i…

Biomonitoring of bisphenols A, F, S in human milk and probabilistic risk assessment for breastfed infants

The present study addresses the presence of bisphenols A (BPA) and its analogs bisphenol F (BPF) and S (BPS) in milk of 120 mothers living in Valencia (Spain) and participating in the BETTERMILK project (year 2015). We also studied the factors that could influence the BPA levels and estimated the exposure and the risk for breast fed infants. The frequency of detection of total (conjugated + unconjugated) and unconjugated-BPA were 83% and 77%. with a geometric mean of 0.29 ng/mL and 0.15 ng/mL, respectively. The frequency of detection was much lower for total-BPF (22%) and total-BPS (1.1%). The place of residence of the mother and the use of personal care products showed significant associat…

Risk assessment of exposure to phthalates in breastfeeding women using human biomonitoring

In this study, we assessed the presence of 14 phthalate metabolites in the urine of 104 lactating mothers from Valencia (Spain) who took part in the human biomonitoring project BETTERMILK. Nine of the metabolites studied showed detection frequencies >80%, whereas the rest of the metabolites presented low detection frequencies (<5%). The concentrations ranged from <LoQ to 1291 ng/mL with monoethyl phthalate showing the highest concentration, with a geometric mean of 34.90 ng/mL. In general, the phthalate metabolite levels quantified in the present study were lower than the urinary levels found in previous studies that involved lactating mothers. The consumption of packaged juices and the fre…

Metabolic adaptation and neuroprotection differ in the retina and choroid in a piglet model of acute postnatal hypoxia.

Hypoxic-ischemic insults to the neonatal brain may cause neurodevelopmental disorders. Vulnerability of different areas of the neural tissue to hypoxic-ischemic stress might be explained by either heterogeneous sensitivity to oxygen or neuroprotective capability. Our understanding of regional heterogeneity is still incomplete in terms of metabolic reconfiguration and/or activation of neuroprotective mechanisms.We studied, by western blotting, reverse-transcriptase PCR, and tandem mass spectrometry, the response of retina and choroid at protein, gene, and metabolic levels during hypoxia in a piglet model of acute postnatal hypoxia.We evidenced a metabolic shift towards glycolysis in choroid …

Comparing Targeted vs. Untargeted MS2 Data-Dependent Acquisition for Peak Annotation in LC-MS Metabolomics

One of the most widely used strategies for metabolite annotation in untargeted LCMS is based on the analysis of MSn spectra acquired using data-dependent acquisition (DDA), where precursor ions are sequentially selected from MS scans based on user-selected criteria. However, the number of MSn spectra that can be acquired during a chromatogram is limited and a trade-off between analytical speed, sensitivity and coverage must be ensured. In this research, we compare four different strategies for automated MS2 DDA, which can be easily implemented in the frame of standard QA/QC workflows for untargeted LC&ndash

Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately asphyxiated term neonates.

Background. Traditionally, asphyxiated newborn infants have been ventilated using 100% oxygen. However, a recent multinational trial has shown that the use of room air was just as efficient as pure oxygen in securing the survival of severely asphyxiated newborn infants. Oxidative stress markers in moderately asphyxiated term newborn infants resuscitated with either 100% oxygen or room air have been studied for the first time in this work. Methods. Eligible term neonates with perinatal asphyxia were randomly resuscitated with either room air or 100% oxygen. The clinical parameters recorded were those of the Apgar score at 1, 5, and 10 minutes, the time of onset of the first cry, and the tim…

miRNomic Signature in Very Low Birth-Weight Neonates Discriminates Late-Onset Gram-Positive Sepsis from Controls

Background and Objectives. Neonatal sepsis is a serious condition with a high rate of mortality and morbidity. Currently, the gold standard for sepsis diagnosis is a positive blood culture, which takes 48–72 h to yield results. We hypothesized that identifying differentially expressed miRNA pattern in neonates with late-onset Gram-positive sepsis would help with an earlier diagnosis and therapy. Methods. This is a prospective observational study in newborn infants with late-onset Gram positive bacterial sepsis and non-septic controls. Complementary to blood culture, an aliquot of 0.5 mL of blood was used to determine small non-coding RNA expression profiling using the GeneChip miRNA 4.0 Arr…

Estudio piloto sobre el estrés y la resiliencia familiar en recién nacidos prematuros

Resumen: Introducción: La prematuridad se acompaña de patología severa, estancias prolongadas en el hospital e incertidumbre acerca del futuro de los pacientes. Estas circunstancias suponen un estrés que puede afectar al funcionamiento de la familia. El objetivo de este trabajo ha sido estudiar los factores de riesgo y de protección del funcionamiento familiar en prematuros comparados con neonatos sanos a término. Población y métodos: Se reclutó a prematuros que cursaron el periodo neonatal con y sin patología (n = 40) a los 24 meses de edad posconcepcional y un grupo control de nacidos a término sanos (n = 31) según datos de la historia clínica. El progenitor cuidador habitual respondió al…

Expired Tidal Volume and Respiratory Rate During Postnatal Stabilization of Newborn Infants Born at Term via Cesarean Delivery

Objective To retrieve evolving respiratory measures in the first minutes after birth in normal neonates born at term using a respiratory function monitor. Study design We evaluated newborn babies delivered at term via cesarean after uncomplicated pregnancies. Immediately after birth, a respiratory function monitor with an adapted flowmeter and a face mask were applied at 2, 5, and 10 minutes after birth for 90 seconds in each period. We analyzed expired and inspired tidal volume, respiratory rate (RR), percentage of leakage, and number of analyzed breaths in each individual infant's recording using a respiratory research software. Results A total of 243 infants completed the study. The fina…

Biomonitoring of parabens in human milk and estimated daily intake for breastfed infants

In this study, we assessed the presence of four parabens in human milk of 120 mothers from Valencia (Spain) which took part in a human biomonitoring project (BETTERMILK). The detection frequency ranges of parabens were 41-60% and 61-89% for unconjugated- and total (unconjugated + conjugated)-parabens, respectively. The concentrations ranged from <LoQ to 31 ng/mL and from <LoQ to 49 ng/mL for unconjugated- and total-parabens, respectively. The frequency of use of some cosmetic products and human milk protein levels were the main predictors of parabens in milk. The study evidences the presence of both conjugated and unconjugated paraben forms in human milk. The newborns estimated daily intake…

Detection of batch effects in liquid chromatography-mass spectrometry metabolomic data using guided principal component analysis.

Metabolomics based on liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for studying dynamic responses of biological systems to different physiological or pathological conditions. Differences in the instrumental response within and between batches introduce unwanted and uncontrolled data variation that should be removed to extract useful information. This work exploits a recently developed method for the identification of batch effects in high throughput genomic data based on the calculation of a delta statistic through principal component analysis (PCA) and guided PCA. Its applicability to LC-MS metabolomic data was tested on two real examples. The first example involved t…

Expression of aquaporins early in human pregnancy

Abstract Background Aquaporins (AQPs) constitute a family of channel proteins implicated in transmembrane water transport. Thirteen different AQPs (AQP0–12) have been described but their precise biologic function still remains unclear. AQPs 1, 3, 4, 8, and 9 expression has been described in human chorion, amnion and placenta; however, AQP4 is the only that has been identified in the first trimester of human pregnancy. Objective To assess multiplicity of AQPs expression from 10th to 14th week gestation. Population and methods Chorionic villi samples (CVS) collected in pregnant women for prenatal diagnosis were analysed by real time-PCR to assess cDNA expression of AQPs 1, 2, 3, 4, 5, 6, 7, 8…

Oxidative stress in asphyxiated term infants resuscitated with 100% oxygen

Although room air is adequate for resuscitating asphyxiated newborn infants, guidelines recommend using 100% oxygen. Hyperoxemia, as has been noted in animal studies, could cause delayed breathing, increased oxygen consumption, and disordered cerebral circulation. In addition, 100% oxygen has caused prolonged oxidation of blood glutathione in neonates. In this study, 51 asphyxiated neonates born at term were randomly assigned to resuscitation with room air (RAR) and 55 to resuscitation with 100% oxygen (OxR). The goal was to learn whether using oxygen for resuscitation triggers oxidative stress. Critical criteria were the Apgar score, the time of the first cry, and sustained respiration. Si…

Exposure and Risk Assessment of Hg, Cd, As, Tl, Se, and Mo in Women of Reproductive Age Using Urinary Biomonitoring

The present study analyzed the exposure and risk assessment of 4 toxic (Hg, Cd, As, Tl) and 2 essential (Se, Mo) elements in 119 Spanish women of reproductive age. The focus was on the elements for which risk-based benchmark, biomonitoring equivalents, or health-related human biomonitoring values have already been established. All elements presented frequencies of detection of 100% (greater than the limit of detection), except for Cd (99%). The 95th percentile concentrations were, for the toxic metals, 358.37 µg/L (total As), 1.10 µg/L (Cd), 0.41 µg/L (Tl), and 3.03 µg/L (total Hg) and, for the essential elements, 68.95 µg/L (total Se) and 154.67 (Mo). We examined sociodemographic factors a…

Does Oxygen Concentration Used for Resuscitation Influence Outcome of Asphyxiated Newly Born Infants Treated With Hypothermia?

To the Editor. — In a recent article, Rutherford et al1 describe the neuroprotective effect of whole-body cooling and selective head cooling in newly born infants suffering from hypoxic-ischemic encephalopathy. MRI studies of infants receiving either of these therapies showed a lesser degree of basal ganglia and thalamic lesions than nontreated controls, which correlates with a better neurologic prognosis. However, no description of the resuscitation maneuvers used is present in the article's “Patients and Methods” section. Thus, the authors do not include details on how many infants were given positive pressure ventilation and, especially, what concentration of oxygen was used, if oxygen s…

Hyperoxemia caused by resuscitation with pure oxygen may alter intracellular redox status by increasing oxidized glutathione in asphyxiated newly born infants

In a prospective, randomized, blinded trial we have studied the effects of resuscitation upon oxygenation in a group of asphyxiated newly born infants receiving room air or 100% oxygen as the gas source. During the acute phase of asphyxia and until the resuscitation procedure concluded, we determined serial blood gases as well as reduced and oxidized glutathione, enzymes involved in the glutathione redox cycle, and antioxidant enzyme activities. The use of 100% oxygen caused a remarkable increase of partial pressures of oxygen in arterial blood, with values that were frequently above physiological levels (>100 mm Hg). In addition, we have found a significant correlation between hyperoxemia …

Biomonitoring of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in human milk: Exposure and risk assessment for lactating mothers and breastfed children from Spain

Abstract The main objective of the present research was to evaluate the levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (dl-PCBs) in the human milk of Spanish lactating women who participated in the BETTERMILK project so that exposure and risk could be assessed for these mothers and their breastfed children. The total ∑PCDD/Fs + dl-PCBs TEQ2005 concentrations in the upper-bound (UB) ranged from 1.29 to 13.48 pg TEQ2005 g−1 lipid. The estimated geometric mean level for the sum of PCDD/F and dl-PCBs was 4.10 and 4.42 pg TEQ2005 g−1 lipid, lower-bound (LB) and UB respectively and were below the reference leve…

Protein-bound tyrosine oxidation, nitration and chlorination by-products assessed by ultraperformance liquid chromatography coupled to tandem mass spectrometry

Abstract Background Free radicals cause alterations in cellular protein structure and function. Oxidized, nitrated, and chlorinated modifications of aromatic amino acids including phenylalanine and tyrosine are reliable biomarkers of oxidative stress and inflammation in clinical conditions. Objective To develop, validate and apply a rapid method for the quantification of known hallmarks of tyrosine oxidation, nitration and chlorination in plasma and tissue proteins providing a snapshot of the oxidative stress and inflammatory status of the organism and of target organs respectively. Material and Methods The extraction and clean up procedure entailed protein precipitation, followed by protei…

Pilot study on stress and resilience in families with premature newborns

Introduction: Prematurity is associated with severe clinical conditions, long hospital stays, and uncertainty about patient outcomes. These circumstances lead to a stressful situation that may affect family functioning. The aim of this study was to study risk and protection factors affecting family functioning in preterm as compared to healthy term infants. Population and methods: Preterm infants with and without pathological conditions (n = 40) were recruited at 24 months post-conception age, together with a control group of healthy term newborn infants (n = 31). Parents or usual caregivers responded to the Inventory of Family Protection Factors and Parental Stress scales. The results were…

The effect of Holder pasteurization on the lipid and metabolite composition of human milk

Human milk (HM) is the gold standard for newborn nutrition. When own mother's milk is not sufficiently available, pasteurized donor human milk becomes a valuable alternative. In this study we analyzed the impact of Holder pasteurization (HoP) on the metabolic and lipidomic composition of HM. Metabolomic and lipidomic profiles of twelve paired HM samples were analysed before and after HoP by liquid chromatography-mass spectrometry (MS) and gas chromatography-MS. Lipidomic analysis enabled the annotation of 786 features in HM out of which 289 were significantly altered upon pasteurization. Fatty acid analysis showed a significant decrease of 22 out of 29 detectable fatty acids. The observed c…

Probiotic characterization of Lactobacillus strains isolated from breast milk and employment for the elaboration of a fermented milk product

Abstract A total of seven strains of lactic acid bacteria (LAB) isolated from breast milk, were investigated for their probiotic properties. Lactobacillus plantarum 5H1 and 5L1 were selected for their beneficial properties and used for probiotic fermented milk manufacture. The fermentation parameters (pH and lactic acid) and LAB viability during fermented milk processing and storage were evaluated. The results showed that the strains had a broad spectrum of antimicrobial activity against pathogenic bacteria and toxigenic fungi. These also evidenced capacity of adhesion and reduction of Salmonella adhesion to Caco-2 cells. During milk fermentation process, an increase in lactic acid content,…

Expression of Human Ubiquitous Aquaporins in Chorial Villus Samples

Background/objectives: Aquaporins (AQPs) are a family of proteins (AQP0-12) ubiquitously expressed acting as cell membrane water channels. AQP 1/3/8/9 expression has been found in human placenta and fetal membranes; however, AQP4 is the only identified in first trimester fetal tissue samples. We aimed to determine AQP mRNA expression in first trimester of pregnancy and compare it to the expression in placenta at delivery. Material and Methods: 26 Chorionic villus (CV) samples and 5 placental samples were collected and analyzed by real time-PCR using Taqman assay (Applied Biosystems®) for human AQP1, 2, 3, 4, 5, 6, 7, 8, 9, 11 and 18S. Results: CV expressed high mRNA levels of AQP1, 3, 9 and…

Milrinone is preferred to levosimendan for mesenteric perfusion in hypoxia-reoxygenated newborn piglets treated with dopamine

INTRODUCTION There is little information regarding the comparative hemodynamic effects of adding milrinone or levosimendan to dopamine infusion in hypoxia-reoxygenated (H-R) newborns. RESULTS Severely hypoxic piglets had cardiogenic shock with depressed cardiac index (CI) and mean arterial pressure (MAP). The hemodynamics deteriorated gradually after initial recovery upon reoxygenation. Heart rate and CI improved with milrinone (D+M) and levosimendan (D+L) administration (P < 0.05 vs. control). Both regimens improved carotid arterial flow and carotid vascular resistance; D+M additionally improved superior mesentric arterial flow (all P < 0.05 vs. control). No effect was found on renal arter…

A New Model of Oxidative Stress in Rat Pups

&lt;i&gt;Background:&lt;/i&gt; With current evidence, no specific oxygen concentration can yet be recommended in the resuscitation of the depressed term neonate. &lt;i&gt;Objectives:&lt;/i&gt; To design a neonatal rat model of resuscitation that mimics birth hypoxia and allows the study of the effects of resuscitation on outcome. &lt;i&gt;Methods:&lt;/i&gt; Several key determinants were established utilizing P12 Sprague-Dawley rat pups. These include the ventilatory settings necessary to maintain normocarbic conditions and the amount and duration of hypoxia required to cause significant disruption of oxidative metabolism in the subjects’ brains. Biochemical and cellular markers of oxidative…

Clinical and immunological aspects of microRNAs in neonatal sepsis

Abstract Neonatal sepsis constitutes a highly relevant public health challenge and is the most common cause of infant morbidity and mortality worldwide. Recent studies have demonstrated that during infection epigenetic changes may occur leading to reprogramming of gene expression. Post-transcriptional regulation by short non-coding RNAs (e.g., microRNAs) have recently acquired special relevance because of their role in the regulation of the pathophysiology of sepsis and their potential clinical use as biomarkers. ~22-nucleotide of microRNAs are not only involved in regulating multiple relevant cellular and molecular functions, such as immune cell function and inflammatory response, but have…

Oxidative and nitrosative stress in acute pancreatitis. Modulation by pentoxifylline and oxypurinol

Item does not contain fulltext Reactive oxygen species are considered mediators of the inflammatory response and tissue damage in acute pancreatitis. We previously found that the combined treatment with oxypurinol - as inhibitor of xanthine oxidase- and pentoxifylline - as inhibitor of TNF-alpha production-restrained local and systemic inflammatory response and decreased mortality in experimental acute pancreatitis. Our aims were (1) to determine the time-course of glutathione depletion and oxidation in necrotizing pancreatitis in rats and its modulation by oxypurinol and pentoxifylline; (2) to determine whether TNF-alpha is responsible for glutathione depletion in acute pancreatitis; and (…

Can stress biomarkers predict preterm birth in women with threatened preterm labor?

Background: Preterm birth is a major paediatric challenge difficult to prevent and with major adverse outcomes. Prenatal stress plays an important role on preterm birth; however, there are few stress-related models to predict preterm birth in women with Threatened Preterm Labor (TPL). Objective: The aim of this work is to study the influence of stress biomarkers on time until birth in TPL women. Methods: Eligible participants were pregnant women between 24 and 31 gestational weeks admitted to the hospital with TPL diagnosis (n = 166). Stress-related biomarkers (a-amylase and cortisol) were determined in saliva samples after TPL diagnosis. Participants were followed-up until labor. A paramet…

Preterm Resuscitation With Low Oxygen Causes Less Oxidative Stress, Inflammation, and Chronic Lung Disease

OBJECTIVE: The goal was to reduce adverse pulmonary adverse outcomes, oxidative stress, and inflammation in neonates of 24 to 28 weeks of gestation initially resuscitated with fractions of inspired oxygen of 30% or 90%. METHODS: Randomized assignment to receive 30% (N = 37) or 90% (N = 41) oxygen was performed. Targeted oxygen saturation values were 75% at 5 minutes and 85% at 10 minutes. Blood oxidized glutathione (GSSG)/reduced glutathione ratio and urinary o-tyrosine, 8-oxo-dihydroxyguanosine, and isoprostane levels, isofuran elimination, and plasma interleukin 8 and tumor necrosis factor α levels were determined. RESULTS: The low-oxygen group needed fewer days of oxygen supplementation …

A preliminary study to assess the impact of maternal age on stress-related variables in healthy nulliparous women

Purpose: Childbearing age has progressively increased in industrialized countries. The impact of this delay on motherhood, however, requires further research. Methods: The study sample included a prospective cohort of healthy nulliparous pregnant women aged between 18 and 40 years (n = 148) assessed at 38 weeks gestation (Time#1, T1), 48 h after birth (Time#2, T2), and 3 months after birth (Time#3, T3). The effect of age on psychological, biological, and social variables was evaluated. Maternal psychological symptoms in terms of depression and anxiety were assessed at T1-T3; and parenting stress at T3. Stress biomarkers (cortisol, alpha-amylase) were determined in mothers at T1-T3. Question…

Hypoxic preconditioning induces neuroprotection against oxidative stress

Brain is an oxyregulator organ, however extremely vulnerable to oxygen. Both high and low oxygen concentrations generate free radicals and may cause oxidative stress and damage because of an insufficient response of the antioxidant system. Hypoxic preconditioning (HP) exerts neuroprotective effects and may be a protecting tool against oxygen fluctuations, thus preventing neuronal damage in events such as ischaemia, acute hypoxia, stroke, or traumatic brain injury, among others. This review aims to discuss the molecular mechanisms involved in the neuroprotective action of HP against oxidative stress and subsequently upon the brain under pro-oxidant conditions. Activation of the antioxidant d…

Biomonitoring of bisphenols A, F, S and parabens in urine of breastfeeding mothers: Exposure and risk assessment

In the present study we used human biomonitoring to assess the internal exposure and the risk to four parabens and three bisphenols in 103 Spanish breastfeeding mothers participating in the BETTERMIILK project. Urinary methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) presented detection frequencies ranging from 12% (BP) to 92% (MP), while bisphenol A (BPA), bisphenol F (BPF) and bisphenol S (BPS) were detected in 76% (BPA) and 20% (BPF, BPS) of the mothers. Average paraben concentrations (geometric mean) ranged from 0.021 ng mL(-1) (BP) to 17.7 ng mL(-1) (MP), whereas bisphenols had geometric means concentrations from 0.042 ng mL(-1) (BPF) to 0.927 ng mL(-1) (…

Role of Redox Signaling, Protein Phosphatases and Histone Acetylation in the Inflammatory Cascade in Acute Pancreatitis: Therapeutic Implications

Acute pancreatitis starts as a local inflammation of the pancreatic tissue but often leads to the systemic inflammatory response syndrome and death by multiple organ failure. Pro-inflammatory cytokines, particularly TNF-alpha and Il-1beta, play a pivotal role together with oxidative stress and glutathione depletion in the inflammatory response in this disease. Most inflammatory mediators act through mitogen activated protein kinases and nuclear factor kB. Nevertheless, elucidation of the precise mechanisms involved in activation and attenuation phases of the inflammatory cascade is still underway. Redox signaling mediated by inactivation of protein phosphatases and histone acetylation trigg…

Xanthine Oxidase Is Involved in Free Radical Production in Type 1 Diabetes

The aim of this work was to study the mechanism of free radical formation in type 1 diabetes and its possible prevention. We have found oxidation of blood glutathione and an increase in plasma lipoperoxide levels in both human type 1 diabetes and experimental diabetes. Peroxide production by mitochondria does not increase in diabetes. On the contrary, the activity of xanthine oxidase, a superoxide-generating enzyme, increases in liver and plasma of diabetic animals. The increase in plasma xanthine oxidase activity may be explained by the increase in the hepatic release of this enzyme, which is not due to nonspecific membrane damage: release of other hepatic enzymes, such as the amino transf…

Target oxygen levels in preterm neonates

To achieve postnatal adaptation newly born infant need to aerate the lungs, reduce pulmonary vascular resistance, and initiate oxygen and carbon dioxide exchange. The cornerstone of newborn resuscitation resides therefore in the establishment of a functional residual capacity and an adequate oxygenation. Recent guidelines have established guidelines concerning oxygen supplementation in preterm infants in the delivery room (DR); however, they are vague and unspecific. Herewith, we will address available information regarding the use of oxygen supplementation in the DR in preterm infants to satisfactorily overcome postnatal adaptation. Introduction: Resuscitation of the newborn is considered …

Elevated protein carbonyl and HIF-1α levels in eyes with proliferative diabetic retinopathy.

Purpose: To evaluate the role of protein carbonyls and hypoxia inducible factor-1a (HIF-1a) in diabetic eyes with proliferative diabetic retinopathy (PDR). Methods: Prospective consecutive controlled observational study was performed. Vitreous samples were collected at the start of the 3-ppp vitrectomy. Protein carbonylation analysis was performed by Western blotting with antibody against 2,4-Dinitrophenol (anti-DNP), following derivatization of protein carbonyls with 2,4 Dinitrophenylhydrazine (DNHP). Protein carbonylation was quantified by scanning densitometry analysis and relativized to the total amount of protein into the ponceau staining of membranes. Vitreous HIF-1 a was determined w…

DNA Methylation Analysis to Unravel Altered Genetic Pathways Underlying Early Onset and Late Onset Neonatal Sepsis. A Pilot Study

Background: Neonatal sepsis is a systemic condition widely affecting preterm infants and characterized by pro-inflammatory and anti-inflammatory responses. However, its pathophysiology is not yet fully understood. Epigenetics regulates the immune system, and its alteration leads to the impaired immune response underlying sepsis. DNA methylation may contribute to sepsis-induced immunosuppression which, if persistent, will cause long-term adverse effects in neonates.Objective: To analyze the methylome of preterm infants in order to determine whether there are DNA methylation marks that may shed light on the pathophysiology of neonatal sepsis.Design: Prospective observational cohort study perf…

Delayed vs Immediate Cord Clamping Changes Oxygen Saturation and Heart Rate Patterns in the First Minutes after Birth

Objective To build arterial oxygen saturation (SpO2) and heart rate (HR) percentiles for the first 10 minutes after birth in term infants born after an uneventful gestation, vaginal delivery, and delayed cord clamping (DCC) for ≥60 seconds, and to compare our results with previous ones constructed after immediate cord clamping. Study design Preductal SpO2, HR, and timing of DCC immediately after complete fetal body expulsion were recorded. The pulse-oximeter was adjusted in the right wrist/hand and set at maximal intensity and measurements performed every 2 seconds. Results A total of 282 term newborn infants were included. The definitive data set comprised of 70 257 SpO2 and 79 746 HR meas…

On-Capillary Surface-Enhanced Raman Spectroscopy: Determination of Glutathione in Whole Blood Microsamples.

Oxidative stress monitoring in the neonatal period supports early outcome prediction and treatment. Glutathione (GSH) is the most abundant antioxidant in most cells and tissues, including whole blood, and its usefulness as a biomarker has been known for decades. To date, the available methods for GSH determination require laborious sample processing and the use of sophisticated laboratory equipment. To the best of our knowledge, no tools suitable for point-of-care (POC) sensing have been reported. Surface-enhanced Raman spectroscopy (SERS), performed in a microvolume capillary measurement cell, is proposed in this study as a robust approach for the quantification of GSH in human whole blood…

Cerebral protection during fetal-to-neonatal transition under hypoxic atmosphere

Newborn asphyxia is a complication during the perinatal period. The use of O2 for resuscitation has been broadly used in clinic. However, it has been demonstrated that oxygen overexposure induces oxidative stress (OS). We speculate that delaying postnatal in the extrauterine oxygenation status would preserve reducing equivalents, enhance redox adaptation, and protect oxyregulator tissues. The objective is evaluated OE status, induced by Fetal-Neonatal Transition (FNT) under different FiO2 conditions, in brain. FiO2 in pregnant mice was reduced from 21% to 14% or not the night before of delivery (G19). 8 hours after birth both group were led to room air (Hx14/21 and Nx21/21 groups) or hypero…

L-cysteine and glutathione metabolism are impaired in premature infants due to cystathionase deficiency.

There are conflicting reports in the literature as to whether L-cysteine is an essential amino acid in premature infants as the result of the absence of hepatic cystathionase activity. To analyze the physiological importance of the cystathionase deficiency, we studied sulfur amino acid metabolism in human neonates of different gestational ages. Plasma cystathionine concentrations are higher in premature infants < or = 32 wk gestation (group 1) than in premature infants of 33-36 wk gestational age (group 2) or in full-term infants (group 3), whereas plasma cysteine concentrations are much lower in group 1 and 2 premature infants than in mature infants. Furthermore, erythrocytes from group 1 …

Reliable determination of new lipid peroxidation compounds as potential early Alzheimer Disease biomarkers.

Lipid peroxidation plays an important role in Alzheimer Disease, so corresponding metabolites found in urine samples could be potential biomarkers. The aim of this work is to develop a reliable ultra-performance liquid chromatography-tandem mass spectrometry analytical method to determine a new set of lipid peroxidation compounds in urine samples. Excellent sensitivity was achieved with limits of detection between 0.08 and 17 nmol L-1, which renders this method suitable to monitor analytes concentrations in real samples. The method's precision was satisfactory with coefficients of variation around 5-17% (infra-day) and 8-19% (inter-day). The accuracy of the method was assessed by analysis o…

Biomonitoring of mercury in hair of breastfeeding mothers living in the Valencian Region (Spain). Levels and predictors of exposure

This study focused on the evaluation of the levels of total mercury in hair among 120 breastfeeding mothers aged 20 to 45-. The concentrations of Hg ranged from 0.07 to 6.87 mu g/g with a geometric mean (GM) of 1.22 mu g/g. This GM is six times higher than the average internal exposure of mothers from other 17 European countries (0.225 mu g/g). Near 70% of mothers presented levels of Hg above the USA EPA internal exposure guideline of 1 mu g/g, and 27% exceeded the EFSA health-based guidance value of 1.9 mu g/g. The multivariate regression analysis revealed that age, smoking and fish consumption (sword fish, small fat fish, small lean fish) were the major predictors of mercury in hair. (C) …

Response to the comment on "Can stress biomarkers predict preterm birth in women with threatened preterm labor?"

Does Pasteurized Donor Human Milk Efficiently Protect Preterm Infants Against Oxidative Stress?

International audience; Pasteurized donor human milk (DHM) is the preferred alternative for infant nutrition when own mother's milk (OMM) is unavailable. Whether DHM is an efficient means for protecting preterm infants from oxidative stress remains unknown. We quantified a panel of oxidative stress biomarkers in urine samples from preterm infants (≤32 weeks of gestation and a birth weight ≤1500 g) receiving ≥80% of feeding volume as either DHM or OMM. The noninvasive in vivo assessment of oxidative stress showed no statistically significant difference between both groups at the time when full enteral nutrition (150 mL/kg body weight) was achieved and until hospital discharge. In addition, t…

Prolonging in utero-like oxygenation after birth diminishes oxidative stress in the lung and brain of mice pups☆

Background Fetal-to-neonatal transition is associated with oxidative stress. In preterm infants, immaturity of the antioxidant system favours supplemental oxygen-derived morbidity and mortality. Objectives To assess if prolonging in utero-like oxygenation during the fetal-to-neonatal transition limits oxidative stress in the lung and brain, improving postnatal adaptation of mice pups. Material and methods Inspiratory oxygen fraction (FiO2) in pregnant mice was reduced from 21% (room air) to 14% (hypoxia) 8–12 h prior to delivery and reset to 21% 6–8 h after birth. The control group was kept at 21% during the procedure. Reduced (GSH) and oxidized (GSSG) glutathione and its precursors [γ-glut…

Do children with overweight respond faster to food-related words?

Abstract Overweight in childhood is a risk factor in developing obesity as an adult, thus having severe consequences on the individuals’ physical health and psychological well-being. Therefore, studying the cognitive and emotional processes that sustain overweight is essential not only at a theoretical level but also to develop effective interventions. In the present experiment, we examined whether children with overweight respond faster to food-related than non-food-related words in a word recognition task: lexical decision. The participants were 24 children diagnosed with exogenous overweight and 24 children with a healthy weight. The stimulus list included positively valenced food-relate…

7,8-hydroxy-2′-deoxyguanosine/2′-deoxiguanosine ratio determined in hydrolysates of brain DNA by ultrachromatrography coupled to tandem mass spectrometry

7,8-hydroxy-2'-deoxyguanosine (8-OHdG) is an abundant DNA lesion formed by oxidation of the nucleoside 2'-deoxyguanosine (2-dG) and one of the most studied and accepted oxidative stress biomarkers. 8-OHdG has a strong carcinogenic potential, and prolonged oxidative stress heightens pathological conditions and especially cancer risk. Our aim was to develop, validate and apply a reliable method to assess DNA oxidation in genomic cellular DNA of sensible target organs such as brain. A procedure to isolate and digest the DNA of brain tissue properly for further detection of 8-OHdG and 2-dG by Ultra Performance Liquid Chromatography tandem Mass Spectrometry (UPLC-MS/MS) was optimized. The UPLC-M…

Impact of Donor Human Milk in the Preterm Very Low Birth Weight Gut Transcriptome Profile by Use of Exfoliated Intestinal Cells

[Background] Own mother’s milk (OMM) is the optimal nutrition for preterm infants. However, pasteurized donor human milk (DHM) is a valid alternative. We explored the differences of the transcriptome in exfoliated epithelial intestinal cells (EEIC) of preterm infants receiving full feed with OMM or DHM.

Analysis of Lipid Peroxidation by UPLC-MS/MS and Retinoprotective Effects of the Natural Polyphenol Pterostilbene

The loss of redox homeostasis induced by hyperglycemia is an early sign and key factor in the development of diabetic retinopathy. Due to the high level of long-chain polyunsaturated fatty acids, diabetic retina is highly susceptible to lipid peroxidation, source of pathophysiological alterations in diabetic retinopathy. Previous studies have shown that pterostilbene, a natural antioxidant polyphenol, is an effective therapy against diabetic retinopathy development, although its protective effects on lipid peroxidation are not well known. Plasma, urine and retinas from diabetic rabbits, control and diabetic rabbits treated daily with pterostilbene were analyzed. Lipid peroxidation was evalu…

Topiramate pharmacokinetics in neonates undergoing therapeutic hypothermia and proposal of an optimised dosing schedule.

Aim The adequate dosing of topiramate in neonates undergoing therapeutic hypothermia has not been established. The aim of this study was to design a dosing schedule capable of providing topiramate serum concentrations within the accepted therapeutic range. Methods Neonates (n = 52) with hypoxic ischaemic encephalopathy and subjected to therapeutic hypothermia were dosed with topiramate, 5 mg/kg on day one and 3 mg/kg on days two to five, to decrease seizure events. A total of 451 topiramate serum concentrations obtained in the patients were used to develop a population pharmacokinetic model using a non-linear mixed-effects modelling approach. Results A one-compartment model with first-order…

Clinicians in 25 countries prefer to use lower levels of oxygen to resuscitate preterm infants at birth.

Aim This study determined current international clinical practice and opinions regarding initial fractional inspired oxygen (FiO2) and pulse oximetry (SpO2) targets for delivery room resuscitation of preterm infants of less than 29 weeks of gestation. Methods An online survey was disseminated to neonatal clinicians via established professional clinical networks using a web-based survey programme between March 9 and June 30, 2015. Results Of the 630 responses from 25 countries, 60% were from neonatologists. The majority (77%) would target SpO2 between the 10th to 50th percentiles values for full-term infants. The median starting FiO2 was 0.3, with Japan using the highest (0.4) and the UK usi…

Sepsis in preterm infants causes alterations in mucosal gene expression and microbiota profiles compared to non-septic twins

Sepsis is a life-threatening condition in preterm infants. Neonatal microbiota plays a pivotal role in the immune system maturation. Changes in gut microbiota have been associated to inflammatory disorders; however, a link with sepsis in the neonatal period has not yet been established. We aimed to analyze gut microbiota and mucosal gene expression using non-invasively obtained samples to provide with an integrative perspective of host-microbe interactions in neonatal sepsis. For this purpose, a prospective observational case-control study was conducted in septic preterm dizygotic twins and their non-septic twin controls. Fecal samples were used for both microbiota analysis and host genome-…

Infrared biospectroscopy for a fast qualitative evaluation of sample preparation in metabolomics.

Liquid chromatography-mass spectrometry (LC-MS) has been increasingly used in biomedicine to study the dynamic metabolomic responses of biological systems under different physiological or pathological conditions. To obtain an integrated snapshot of the system, metabolomic methods in biomedicine typically analyze biofluids (e.g. plasma) that require clean-up before being injected into LC-MS systems. However, high resolution LC-MS is costly in terms of resources required for sample and data analysis and care must be taken to prevent chemical (e.g. ion suppression) or statistical artifacts. Because of that, the effect of sample preparation on the metabolomic profile during metabolomic method d…

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

BACKGROUND: Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences. METHODS: This was a prospective observational double-cohort study conducted in VLBW (&amp;lt;1500 g) infants with culture-positive bacterial sepsis and non-septic matched controls. Blood samples were collected as soon as clinical signs of sepsis were identified and before antibiotics were initiated. Total RNA was processed for genome-wide expression an…

Sex-dependent changes in the pulmonary vasoconstriction potential of newborn rats following short-term oxygen exposure

Chronic exposure to supplemental oxygen (O(2)) induces lung damage and mortality in a sex-dependent manner. The effect of short-term hyperoxia on the newborn pulmonary vasculature is unknown but is, however, of clinical significance in the neonatal resuscitation context. We hypothesize that short-term hyperoxia has a sex-dependent effect on the pulmonary vasculature.Following 1-h 100% O(2) exposure, the pulmonary arteries and lung tissues of newborn rats were evaluated.Superoxide dismutase 3 (SOD3) expression in female pups' lungs was increased as compared with that in the lungs of male pups. As compared with air-treated pups, the response of male pups to thromboxane was increased by O(2), …

Assessment of oxidative damage to proteins and DNA in urine of newborn infants by a validated UPLC-MS/MS approach

The assessment of oxidative stress is highly relevant in clinical Perinatology as it is associated to adverse outcomes in newborn infants. This study summarizes results from the validation of an Ultra Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) method for the simultaneous quantification of the urinary concentrations of a set of endogenous biomarkers, capable to provide a valid snapshot of the oxidative stress status applicable in human clinical trials, especially in the field of Perinatology. The set of analytes included are phenylalanine (Phe), para-tyrosine (p-Tyr), ortho-tyrosine (o-Tyr), meta-tyrosine (m-Tyr), 3-NO2-tyrosine (3NO(2)-Tyr), 3-Cl-tyrosine (3Cl-T…

Attentional biases towards emotional scenes in autism spectrum condition: An eye-tracking study.

Abstract Background Different attentional processing of emotional information may underlie social impairments in Autism Spectrum Condition (ASC). It has been hypothesized that individuals with ASC show hypersensitivity to threat, which may be related to an avoidance behaviour. However, research on the attentional processing of emotional information in autism is inconclusive. Aim To examine the attentional processing biases of 27 children with ASC and 25 typically developed (TD) participants. Methods and procedures The initial orienting of attention, the attentional engagement, and the attentional maintenance to complex emotional scenes in competition (happy, neutral, threatening, sad) were …

Antenatal Steroids and Antioxidant Enzyme Activity in Preterm Infants: Influence of Gender and Timing

Antenatal steroids have improved the survival of preterm infants; however, the mechanism of action is not fully understood. We aimed to establish an association between antenatal steroids and antioxidant activity and postnatal oxidative stress. In a prospective cohort study, extremely preterm neonates receiving antenatal steroids (CORT) or not (NOCORT) were enrolled. An association between antenatal steroids and activities of antioxidant enzymes and glutathione cycle enzymes in cord blood was found. In addition, reduced oxidative stress (GSH/GSSG ratio, CORT vs. NOCORT, 35.68 + or - 12.20 vs. 28.38 + or - 9.92; p < 0.01) and, decreased oxidation of proteins (ortho-tyrosine/phenylalanine rat…

Anxiety and depressive symptoms, and stress biomarkers in pregnant women after in vitro fertilization: a prospective cohort study.

STUDY QUESTION Does in vitro fertilization (IVF) affect the course of anxiety and depressive symptoms as well as physiological stress from pregnancy to postpartum period? SUMMARY ANSWER IVF mothers have more anxiety symptoms and higher stress biomarker levels but fewer depression symptoms than natural conception mothers at the third trimester of pregnancy, but these differences are negligible during postpartum period. WHAT IS KNOWN ALREADY Cross-sectional studies have found an association between IVF and high stress levels during the prenatal period. There is, however, no follow-up study about the IVF effect on the mental health status from pregnancy to postpartum, adopting simultaneous mea…

Impact of maternal age on infants' emotional regulation and psychomotor development

AbstractBackgroundMaternal age has progressively increased in industrialized countries. Most studies focus on the consequences of delayed motherhood for women's physical and mental health, but little is known about potential effects on infants' neurodevelopment. This prospective study examines the association between maternal age and offspring neurodevelopment in terms of both psychomotor development (Ages &amp; Stages Questionnaires-3) and emotional competences (Early Childhood Behavior Questionnaire).MethodsWe evaluated a cohort of healthy pregnant women aged 20–41 years and their offspring, assessed at 38 weeks gestation (n= 131) and 24 months after birth (n= 101). Potential age-related …

The role of attentional biases to appetitive stimuli in childhood overweight

Overweight during childhood constitutes a high-risk factor for adult obesity. An abnormal attention to food stimuli (i.e., a bias) has been suggested as an underlying mechanism to the onset and/or maintenance of obesity. Previous literature supports the existence of a biased attention toward food stimuli in adults with obesity. However, it is unknown whether this attentional bias occurs in high-risk children for adult obesity. We aimed to examine attentional biases to food at different stages of attention processing in overweight children. A dot-probe task was applied to 25 children with overweight and 25 healthy-weight children (8-12 years old). Attentional preference to or avoidance of pl…

Disulfide stress: a novel type of oxidative stress in acute pancreatitis.

Glutathione oxidation and protein glutathionylation are considered hallmarks of oxidative stress in cells because they reflect thiol redox status in proteins. Our aims were to analyze the redox status of thiols and to identify mixed disulfides and targets of redox signaling in pancreas in experimental acute pancreatitis as a model of acute inflammation associated with glutathione depletion. Glutathione depletion in pancreas in acute pancreatitis is not associated with any increase in oxidized glutathione levels or protein glutathionylation. Cystine and homocystine levels as well as protein cysteinylation and γ-glutamyl cysteinylation markedly rose in pancreas after induction of pancreatitis…

34 Early Gene Regulation in Retina and Choroid After Ashpyxia and Resuscitation in Newborn Piglets

34 Early Gene Regulation in Retina and Choroid After Ashpyxia and Resuscitation in Newborn Piglets

Analysis of multi-source metabolomic data using joint and individual variation explained (JIVE).

Metabolic profiling is increasingly being used for understanding biological processes but there is no single analytical technique that provides a complete quantitative or qualitative profiling of the metabolome. Data fusion (i.e. joint analysis of data from multiple sources) has the potential to circumvent this issue facilitating knowledge discovery and reliable biomarker identification. Another field of application of data fusion is the simultaneous analysis of metabolomic changes through several biofluids or tissues. However, metabolomics typically deals with large datasets, with hundreds to thousands of variables and the identification of shared and individual factors or structures acros…

Communication deficits and avoidance of angry faces in children with autism spectrum disorder.

Abstract Background Understanding how emotional faces are processed is important to help characterize the social deficits in Autism Spectrum Disorder (ASD). Aims We examined: (i) whether attention is modulated by emotional facial expression; (ii) the time course of the attentional preferences (short vs. long stimulus presentation rates); and (iii) the association between attentional biases and autistic symptomatology. Method and procedures We applied a dot-probe experiment with emotional faces (happy, sad, and angry). The sample was composed of ASD children without additional language and/or intellectual impairments (n = 29) and age-matched Typically Developing (TD) children (n = 29). Outco…

Metabolomic Analysis of the Effect of Postnatal Hypoxia on the Retina in a Newly Born Piglet Model

The availability of reliable biomarkers of brain injury secondary to birth asphyxia could substantially improve clinical grading, therapeutic intervention strategies, and prognosis. In this study, changes in the metabolome of retinal tissue caused by profound hypoxia in an established neonatal piglet model were investigated using an ultra performance liquid chromatography - quadrupole time of flight mass spectrometry (UPLC-QTOFMS) untargeted metabolomic approach, which included Partial Least Squares - Discriminant Analysis (PLSDA) multivariate data analysis. The initial identification of a set of discriminant metabolites from UPLC-QTOFMS data was confirmed by target UPLC-MS/MS and allowed t…

Monitoring of system conditioning after blank injections in untargeted UPLC-MS metabolomic analysis

AbstractUltra-performance liquid chromatography – mass spectrometry (UPLC-MS) is widely used for untargeted metabolomics in biomedical research. To optimize the quality and precision of UPLC-MS metabolomic analysis, evaluation of blank samples for the elimination of background features is required. Although blanks are usually run either at the beginning or at the end of a sequence of samples, a systematic analysis of their effect of the instrument performance has not been properly documented. Using the analysis of two common bio-fluids (plasma and urine), we describe how the injection of blank samples within a sequence of samples may affect both the chromatographic and MS detection performa…

ATR-FTIR spectroscopy for the routine quality control of exosome isolations

Abstract Exosomes are nanosized vesicles containing specific cargos of DNA, RNA, proteins, metabolites, and intracellular and membrane lipids. Exosome isolation needs to be optimized carefully depending on the type of biofluid and tissue and the retrieved exosomes need to be characterized. The main objective of this study was to determine the feasibility of a multimodal analysis of Attenuated Total Reflectance – Fourier Transform Infrared (ATR-FTIR) spectroscopy and UPLC–QqTOF-MSMS for the development of a routine quality control tool of isolated exosomes and the rapid characterization of their lipid profiles and total protein content. Using human milk as model example, exosomes were isolat…

Trajectories of stress biomarkers and anxious-depressive symptoms from pregnancy to postpartum period in women with a trauma history

Background: Cross-sectional studies have found that a trauma history can be associated with anxious-depressive symptomatology and physiological stress dysregulation in pregnant women. Methods: This prospective study examines the trajectories of both anxiety and depressive symptoms and salivary cortisol and α-amylase biomarkers from women with (n = 42) and without (n = 59) a trauma history at (i) 38th week of gestation (T1), (ii) 48 hours after birth (T2), and (iii) three months after birth (T3). Results: The quantile regression model showed that trauma history was associated with higher cortisol levels at T1 and this difference was sustained along T2 and T3. Conversely, there were no signif…