Epigenetic influences in the development of bronchopulmonary dysplasia

Abstract Lung development is orchestrated by highly integrated morphogenic programs of interrelated patterns of gene and protein expression. Both genetic and epigenetic influences may alter the developing lung in the canalicular and saccular phase of lung development that lead to the development of bronchopulmonary dysplasia (BPD). Maternal exposures to toxins, and especially tobacco smoke associated nicotine nitrosamine ketones, fetal and neonatal infections (with or without chorioamnionitis) and techniques of neonatal ventilator management including surfactant therapy in concert with innate genetic susceptibility have life-long consequences for the infant afflicted with BPD. Exposure to supplemental oxygen poses another threat to the prematurely newborn and increases the risk for BPD and retinopathy of prematurity, but other effects in later life have been note among infants given oxygen as newborns. Thus a greater focus on these epigenetic influences and novel strategies to care for the preterm infant will hopefully reduce the worldwide burden of BPD and increase awareness regarding epigenetic mechanisms that determine long term health and well-being

Aerosol delivery to ventilated newborn infants: historical challenges and new directions

There are several aerosolized drugs which have been used in the treatment of neonatal respiratory illnesses, such as bronchodilators, diuretics, and surfactants. Preclinical in vitro and in vivo studies identified a number of variables that affect aerosol efficiency, including particle size, aerosol flows, nebulizer choice, and placement. Nevertheless, an optimized aerosol drug delivery system for mechanically ventilated infants still does not exist. Increasing interest in this form of drug delivery requires more controlled and focused research of drug/device combinations appropriate for the neonatal population. In the present article, we review the research that has been conducted thus far and discuss the next steps in developing the optimal aerosol delivery system for use in mechanically ventilated neonates

Association of low ficolin-2 concentration in cord serum with respiratory distress syndrome in preterm newborns

IntroductionFicolin-2 is a serum pattern recognition molecule, involved in complement activation via the lectin pathway. This study aimed to investigate the association of ficolin-2 concentration in cord blood serum with complications related to premature birth.Methods546 premature neonates were included. The concentration of ficolin-2 in cord blood serum was determined by a sandwich TRIFMA method. FCN2 genetic variants were analysed with RFLP-PCR, allele-specific PCR, Sanger sequencing or allelic discrimination using TaqMan probes method.FindingsCord blood serum ficolin-2 concentration correlated positively with Apgar score and inversely with the length of hospitalisation and stay at Neonatal Intensive Care Unit (NICU). Multivariate logistic regression analysis indicated that low ficolin-2 increased the possibility of respiratory distress syndrome (RDS) diagnosis [OR=2.05, 95% CI (1.24-3.37), p=0.005]. Median ficolin-2 concentration was significantly lower in neonates with RDS than in premature babies without this complication, irrespective of FCN2 gene polymorphisms localised to promoter and 3’untranslated regions: for patients born <33 GA: 1471 ng/ml vs. 2115 ng/ml (p=0.0003), and for patients born ≥33 GA 1610 ng/ml vs. 2081 ng/ml (p=0.012). Ficolin-2 level was also significantly lower in neonates requiring intubation in the delivery room (1461 ng/ml vs. 1938 ng/ml, p=0.023) and inversely correlated weakly with the duration of respiratory support (R=-0.154, p<0.001). Interestingly, in the neonates born at GA <33, ficolin-2 concentration permitted differentiation of those with/without RDS [AUC=0.712, 95% CI (0.612-0.817), p<0.001] and effective separation of babies with mild RDS from those with moderate/severe form of the disease [AUC=0.807, 95% CI (0.644-0.97), p=0.0002].ConclusionLow cord serum ficolin-2 concentration (especially in neonates born at GA <33 weeks) is associated with a higher risk of developing moderate/severe RDS, requiring respiratory support and intensive care

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO):Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017.</p

Potencijalna korist meteoroloških informacija u prometu

U uvodu se ukazuje na ulogu i značaj meteorološke službe u valorizaciji prometa Republike Hrvatske. U drugom poglavlju daju se ciljevi i nabrajaju korisnici meteoroloških informacija u prometu, objašnjava priroda korisničkih zahtjeva i njihova identifikacija, vrste i sadržaj meteoroloških informacija, odnos korisnika prema ovim informacijama, te načini ostvarenja potencijalnih koristi u prometu. U trećem poglavlju obrazlaže se potreba upoznavanja meteorologa s djelatnostima korisnika informacija te osposobljavanje korisnika, i svih onih koji po prirodi posla dolaze u dodir s meteorološkim informacijama na putu od meteorologa do korisnika, kako bi se one optimalno koristile. U četvrtom poglavlju prikazan je sastav simulacijskog modela za istraživanje i primjenu potencijalnih koristi meteoroloških informacija u prometu, te se ukratko opisuje metodologija za njihovo efikasno korištenje od strane korisnika primjenom cost/benefit analize na jednostavnom primjeru