Effect of postnatal malnutrition on hyperoxia-induced newborn lung development

Several factors are associated with bronchopulmonary dysplasia. Among them, hyperoxia and lung immaturity are considered to be fundamental; however, the effect of malnutrition is unknown. Our objective was to evaluate the effects of 7 days of postnatal malnutrition and hyperoxia on lung weight, volume, water content, and pulmonary morphometry of premature rabbits. After c-section, 28-day-old New Zealand white rabbits were randomized into four groups: control diet and room air (CA, N = 17), control diet and ≥95% O2 (CH, N = 17), malnutrition and room air (MA, N = 18), and malnutrition and ≥95% O2 (MH, N = 18). Malnutrition was defined as a 30% reduction of all the nutrients provided in the control diet. Treatments were maintained for 7 days, after which histological and morphometric analyses were conducted. Lung slices were stained with hematoxylin-eosin, modified orcein-resorcin or picrosirius. The results of morphometric analysis indicated that postnatal malnutrition decreased lung weight (CA: 0.83 ± 0.19; CH: 0.96 ± 0.28; MA: 0.65 ± 0.17; MH: 0.79 ± 0.22 g) and water content, as well as the number of alveoli (CA: 12.43 ± 3.07; CH: 8.85 ± 1.46; MA: 7.33 ± 0.88; MH: 6.36 ± 1.53 x 10-3/mm) and elastic and collagen fibers. Hyperoxia reduced the number of alveoli and increased septal thickening and the mean linear intercept. The reduction of alveolar number, collagen and elastic fibers was intensified when malnutrition and hyperoxia were associated. These data suggest that dietary restriction enhances the magnitude of hyperoxia-induced alveolar growth arrest and lung parenchymal remodeling. It is interesting to consider the important influence of postnatal nutrition upon lung development and bronchopulmonary dysplasia.FAPES

Perinatal Factors Associated With Early Deaths Of Preterm Infants Born In Brazilian Network On Neonatal Research Centers [fatores Perinatais Associados Ao óbito Precoce Em Prematuros Nascidos Nos Centros Da Rede Brasileira De Pesquisas Neonatais]

Objective: To evaluate perinatal factors associated with early neonatal death in preterm infants with birth weights (BW) of 400-1,500 g. Methods: A multicenter prospective cohort study of all infants with BW of 400-1,500 g and 23-33 weeks of gestational age (GA), without malformations, who were born alive at eight public university tertiary hospitals in Brazil between June of 2004 and May of 2005. Infants who died within their first 6 days of life were compared with those who did not regarding maternal and neonatal characteristics and morbidity during the first 72 hours of life. Variables associated with the early deaths were identified by stepwise logistic regression. Results: A total of 579 live births met the inclusion criteria. Early deaths occurred in 92 (16%) cases, varying between centers from 5 to 31%, and these differences persisted after controlling for newborn illness severity and mortality risk score (SNAPPE-II). According to the multivariate analysis, the following factors were associated with early intrahospital neonatal deaths: gestational age of 23-27 weeks (odds ratio - OR = 5.0; 95%CI 2.7-9.4), absence of maternal hypertension (OR = 1.9; 95%CI 1.0-3.7), 5th minute Apgar 0-6 (OR = 2.8; 95%CI 1.4-5.4), presence of respiratory distress syndrome (OR=3.1;95%CI 1.4-6.6), and network center of birth. Conclusion: Important perinatal factors that are associated with early neonatal deaths in very low birth weight preterm infants can be modified by interventions such as improving fetal vitality at birth and reducing the incidence and severity of respiratory distress syndrome. The heterogeneity of early neonatal rates across the different centers studied indicates that best clinical practices should be identified and disseminated throughout the country. Copyright © 2008 by Sociedade Brasileira de Pediatria.844300307Joseph, K.S., Liston, R.M., Dodds, L., Dahlgren, L., Allen, A.C., Socioeconomic status and perinatal outcomes in a setting with universal access to essential health care services (2007) CMAJ, 177, pp. 583-590Mathews, T.J., MacDorman, M.F., Infant mortality statistics from the 2004 period linked birth/infant death data set (2007) Natl Vital Stat Rep, 55, pp. 1-32Kramer, M.S., Demissie, K., Yang, H., Platt, R.W., Sauve, R., Liston, R., The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System (2000) JAMA, 284, pp. 843-849Ananth, C.V., Vintzileos, A.M., Epidemiology of preterm birth and its clinical subtypes (2006) J Matern Fetal Neonatal Med, 19, pp. 773-782Brasil. Ministério da Saúde. DATASUS. Informaç ões de Saúde-Estatísticas Vitais- Mortalidade e Nascidos Vivos: nascidos vivos desde 1994. http://tabnet.datasus.gov.br/cgi/deftohtm.exe? sinasc/cnv/nvuf.def. Acesso: 29.10.2007Brasil. Ministério da Saúde. DATASUS. Informaç ões de Saúde-Estatísticas Vitais- Mortalidade e Nascidos Vivos: óbitos infantis - desde 1979. http://tabnet.datasus.gov.br/cgi/ deftohtm.exe?sim/cnv/infuf.def. Acesso: 29.10.2007Barros, F.C., Diaz-Rossello, J.L., The quality of care of very low birth weight babies in Brazil (2007) J Pediatr (Rio J), 83, pp. 5-6Horbar, J.D., Badger, G.J., Carpenter, J.H., Fanaroff, A.A., Kilpatrick, S., LaCorte, M., Trends in mortality and morbidity for very low birth weight infants, 1991-1999 (2002) Pediatrics, 110, pp. 143-151Fanaroff AA, Stoll BJ, Wright LL, Carlo WA, Ehrenkranz RA, Stark AR, et al. Trends in neonatal morbidity and mortality for very low birth weight infants. Am J Obstet Gynecol. 2007;196:147.e1-8(2004) Infra-estrutura para atendimento integral ao recém-nascido, , http://www.sbp.com.br/show_item2.cfm?id_categoria=21&id_detalhe=1636&tipo_detalhe=s.Access:02.11.2007, Departamento de Neonatologia da Sociedade Brasileira de PediatriaBallard, J.L., Khoury, J.C., Wedig, K., Wang, L., Eilers-Walsman, B.L., Lipp, R., New Ballard Score, expanded to include extremely premature infants (1991) J Pediatr, 119, pp. 417-423Alexander, G.R., Himes, J.H., Kaufman, R.B., Mor, J., Kogan, M., A United States national reference for fetal growth (1996) Obstet Gynecol, 87, pp. 163-168Kattwinkel, J., (2000) Textbook of Neonatal Resuscitation, , 4th ed. Chicago, IL: American Academy of Pediatrics/American Heart Association;Richardson, D.K., Corcoran, J.D., Escobar, G.J., Lee, S.K., SNAP-II and SNAPPE-II: Simplified newborn illness severity and mortality risk scores (2001) J Pediatr, 138, pp. 92-100El-Metwally D, Vohr B, Tucker R. Survival and neonatal morbidity at the limits of viability in the mid 1990s: 22 to 25 weeks. J Pediatr. 2000;137:616-22Costeloe, K., Hennessy, E., Gibson, A.T., Marlow, N., Wilkinson, A.R., The EPICure study: Outcomes to discharge from hospital for infants born at the threshold of viability (2000) Pediatrics, 106, pp. 659-671MacDonald, H., American Academy of Pediatrics. Committee on Fetus and Newborn. Perinatal care at the threshold of viability (2002) Pediatrics, 110, pp. 1024-1027Jain, L., Raju, T.N., editors. Late preterm pregnancy and the newborn (2006) Clin Perinatol, 33, pp. 751-972de Kleine, M.J., den Ouden, A.L., Kollee, L.A., Ilsen, A., van Wassenaer, A.G., Brand, R., Lower mortality but higher neonatal morbidity over a decade in very preterm infants (2007) Paediatr Perinat Epidemiol, 21, pp. 15-25Moro, M., Figueras-Aloy, J., Fernández, C., Doménech, E., Jiménez, R., Pérez-Rodríguez, J., Mortality for newborns of birthweight less than 1,500 g in Spanish neonatal units (2002-2005) (2007) Am J Perinatol, 24, pp. 593-601Drumond Ede, F., Machado, C.J., Franca, E., Early neonatal mortality: An analysis of multiple causes of death by the Grade of Membership method (2007) Cad Saude Publica, 23, pp. 157-166Richardson, D.K., Shah, B.L., Frantz 3rd, I.D., Bednarek, F., Rubin, L.P., McCormick, M.C., Perinatal risk and severity of illness in newborns at 6 neonatal intensive care units (1999) Am J Public Health, 89, pp. 511-516Horbar, J.D., Rogowski, J., Plsek, P.E., Delmore, P., Edwards, W.H., Hocker, J., Collaborative quality improvement for neonatal intensive care. NIC/Q Project Investigators of the Vermont Oxford Network (2001) Pediatrics, 107, pp. 14-22Vohr, B.R., Wright, L.L., Dusick, A.M., Perritt, R., Poole, W.K., Tyson, J.E., Center differences and outcomes of extremely low birth weight infants (2004) Pediatrics, 113, pp. 781-789Horbar JD, Plsek PE, Leahy KNIC/Q 2000. NIC/Q 2000: establishing habits for improvement in neonatal intensive care units. Pediatrics. 2003;111:e397-410Evans, N., Hutchinson, J., Simpson, J.M., Donoghue, D., Darlow, B., Henderson-Smart, D., Prenatal predictors of mortality in very preterm infants cared for in the Australian and New Zealand Neonatal Network (2007) Arch Dis Child Fetal Neonatal Ed, 92, pp. F34-F40Walther, F.J., Withholding treatment, withdrawing treatment, and palliative care in the neonatal intensive care unit (2005) EarlyHumDev, 81, pp. 965-972von Dadelszen, P., Magee, L.A., Taylor, E.L., Muir, J.C., Stewart, S.D., Sherman, P., Maternal hypertension and neonatal outcome among small for gestational age infants (2005) Obstet Gynecol, 106, pp. 335-339Casey, B.M., McIntire, D.D., Leveno, K.J., The continuing value of the Apgar score for the assessment of newborn infants (2001) N Engl J Med, 344, pp. 467-471,308-31

Identification of potential non-invasive biomarkers in diastrophic dysplasia.

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by pathogenic variants in the SLC26A2 gene encoding for a cell membrane sulfate/chloride antiporter crucial for sulfate uptake and glycosaminoglycan (GAG) sulfation. Research on a DTD animal model has suggested possible pharmacological treatment approaches. In view of future clinical trials, the identification of non-invasive biomarkers is crucial to assess the efficacy of treatments. Urinary GAG composition has been analyzed in several metabolic disorders including mucopolysaccharidoses. Moreover, the N-terminal fragment of collagen X, known as collagen X marker (CXM), is considered a real-time marker of endochondral ossification and growth velocity and was studied in individuals with achondroplasia and osteogenesis imperfecta. In this work, urinary GAG sulfation and blood CXM levels were investigated as potential biomarkers for individuals affected by DTD. Chondroitin sulfate disaccharide analysis was performed on GAGs isolated from urine by HPLC after GAG digestion with chondroitinase ABC and ACII, while CXM was assessed in dried blood spots. Results from DTD patients were compared with an age-matched control population. Undersulfation of urinary GAGs was observed in DTD patients with some relationship to the clinical severity and underlying SLC26A2 variants. Lower than normal CXM levels were observed in most patients, even if the marker did not show a clear pattern in our small patient cohort because CXM values are highly dependent on age, gender and growth velocity. In summary, both non-invasive biomarkers are promising assays targeting various aspects of the disorder including overall metabolism of sulfated GAGs and endochondral ossification

Accelerated forgetting of real-life events in Transient Epileptic Amnesia.

addresses: Cognitive and Behavioural Neurology, Peninsula Medical School, University of Exeter, Exeter, UK.types: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2010 Elsevier. NOTICE: This is the author’s version of a work accepted for publication by Elsevier. Changes resulting from the publishing process, including peer review, editing, corrections, structural formatting and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuropsychologia, 2010, Vol. 48, Issue 11, pp. 3235 – 3244 DOI: http://dx.doi.org/10.1016/j.neuropsychologia.2010.07.001Transient Epileptic Amnesia (TEA) is a form of temporal lobe epilepsy associated with ictal and interictal memory disturbance. Some patients with TEA exhibit Accelerated Long-term Forgetting (ALF), in which memory for verbal and non-verbal material is retained normally over short delays but fades at an unusually rapid rate over days to weeks. This study addresses three questions about ALF in TEA: (i) whether real-life events undergo ALF in a similar fashion to laboratory-based stimuli; (ii) whether ALF can be detected within 24h; (iii) whether procedural memories are susceptible to ALF. Eleven patients with TEA and eleven matched healthy controls wore a novel, automatic camera, SenseCam, while visiting a local attraction. Memory for images of events was assessed on the same day and after delays of one day, one week, and three weeks. Forgetting of real-life events was compared with forgetting of a word list and with performance on a procedural memory task. On the day of their excursion, patients and controls recalled similar numbers of primary events, associated secondary details (contiguous events, thoughts and sensory information) and items from the word list. In contrast, patients showed ALF for primary events over three weeks, with ALF for contiguous events, thoughts and words over the first day. Retention on the procedural memory task was normal over three weeks. The results indicate that accelerated forgetting in TEA: (i) affects memory for real-life events as well as laboratory stimuli; (ii) is maximal over the first day; and (iii) is specific to declarative memories

Effects Of Therapeutic Approach On The Neonatal Evolution Of Very Low Birth Weight Infants With Patent Ductus Arteriosus

Objective To analyze the effects of treatment approach on the outcomes of newborns (birth weight [BW] < 1,000 g) with patent ductus arteriosus (PDA), from the Brazilian Neonatal Research Network (BNRN) on: death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH III/IV), retinopathy of prematurity requiring surgical (ROPsur), necrotizing enterocolitis requiring surgery (NECsur), and death/BPD.Methods This was a multicentric, cohort study, retrospective data collection, including newborns (BW < 1000 g) with gestational age (GA) < 33 weeks and echocardiographic diagnosis of PDA, from 16 neonatal units of the BNRN from January 1, 2010 to Dec 31, 2011. Newborns who died or were transferred until the third day of life, and those with presence of congenital malformation or infection were excluded. Groups: G1 - conservative approach (without treatment), G2 - pharmacologic (indomethacin or ibuprofen), G3 - surgical ligation (independent of previous treatment). Factors analyzed: antenatal corticosteroid, cesarean section, BW, GA, 5 min. Apgar score < 4, male gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II), respiratory distress syndrome (RDS), late sepsis (LS), mechanical ventilation (MV), surfactant (< 2 h of life), and time of MV. Outcomes: death, O2 dependence at 36 weeks (BPD36wks), IVH III/IV, ROPsur, NECsur, and death/BPD36wks. Statistics: Student's t-test, chi-squared test, or Fisher's exact test; Odds ratio (95% CI); logistic binary regression and backward stepwise multiple regression. Software: MedCalc (Medical Calculator) software, version 12.1.4.0. p-values < 0.05 were considered statistically significantResults 1,097 newborns were selected and 494 newborns were included: G1 - 187 (37.8%), G2 - 205 (41.5%), and G3 - 102 (20.6%). The highest mortality was observed in G1 (51.3%) and the lowest in G3 (14.7%). The highest frequencies of BPD36wks (70.6%) and ROPsur were observed in G3 (23.5%). The lowest occurrence of death/BPD36wks occurred in G2 (58.0%). Pharmacological (OR 0.29; 95% CI: 0.14-0.62) and conservative (OR 0.34; 95% CI: 0.14-0.79) treatments were protective for the outcome death/BPD36wks. Conclusion The conservative approach of PDA was associated to high mortality, the surgical approach to the occurrence of BPD36wks and ROPsur, and the pharmacological treatment was protective for the outcome death/BPD36wks.906616623Clyman, R.I., Mechanisms regulating the ductus arteriosus (2006) Biol Neonate., 89, pp. 330-335Benitz, W.E., Treatment of persistent patent ductus arteriosus in preterm infants: Time to accept the null hypothesis? (2010) J Perinatol., 30, pp. 241-252Redline, R.W., Wilson-Costello, D., Hack, M., Placental and other perinatal risk factors for chronic lung disease in very low birth weight infants (2002) Pediatr Res., 52, pp. 713-719Evans, N., Kluckow, M., Early ductal shunting and intraventricular haemorrhage in ventilated preterm infants (1996) Arch Dis Child Fetal Neonatal Ed., 75, pp. 183-F186Noerr, B., Current controversies in the understanding of necrotizing enterocolitis Part 1 (2003) Adv Neonatal Care., 3, pp. 107-120Koch, J., Hensley, G., Roy, L., Brown, S., Ramaciotti, C., Rosenfeld, C.R., Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less (2006) Pediatrics., 117, pp. 1113-1121Afiune, J.Y., Singer, J.M., Leone, C.R., Evolução ecocardiográfica de recém-nascidos com persistência do canal arterial (2005) J Pediatr (Rio J)., 81, pp. 454-460Sosenko, I.R., Fajardo, M.F., Claure, N., Bancalari, E., Timing of patent ductus arteriosus treatment and respiratory outcome in premature infants: A double-blind randomized controlled trial (2012) J Pediatr., 160, pp. 929-935. , e1Laughon, M.M., Simmons, M.A., Bose, C.L., Patency of the ductus arteriosus in the premature infant: Is it pathologic? Should it be treated? (2004) Curr Opin Pediatr., 16, pp. 146-151Clyman, R.I., Chorne, N., Patent ductus arteriosus: Evidence for and against treatment (2007) J Pediatr., 150, pp. 216-219Bose, C.L., Laughon, M., Treatment to prevent patency of the ductus arteriosus: Beneficial or harmful? (2006) J Pediatr., 148, pp. 713-714Clyman, R.I., Couto, J., Murphy, G.M., Patent ductus arteriosus: Are current neonatal treatment options better or worse than no treatment at all? (2012) Semin Perinatol., 36, pp. 123-129Alexander, G.R., Himes, J.H., Kaufman, R.B., Mor, J., Kogan, M., A United States national reference for fetal growth (1996) Obstet Gynecol., 87, pp. 163-168Jhaveri, N., Moon-Grady, A., Clyman, R.I., Early surgical ligation versus a conservative approach for management of patent ductus arteriosus that fails to close after indomethacin treatment (2010) J Pediatr., 157. , 381-7, 387.e1Clyman, R., Cassady, G., Kirklin, J.K., Collins, M., Philips, J.B., III, The role of patent ductus arteriosus ligation in bronchopulmonary dysplasia: Reexamining a randomized controlled trial (2009) J Pediatr., 154, pp. 873-876Mirea, L., Sankaran, K., Seshia, M., Ohlsson, A., Allen, A.C., Aziz, K., Treatment of patent ductus arteriosus and neonatal mortality/morbidities: Adjustment for treatment selection bias (2012) J Pediatr., 161, pp. 689-694. , e1Youn, Y., Lee, J.Y., Lee, J.H., Kim, S.Y., Sung, I.K., Lee, J.Y., Impact of patient selection on outcomes of PDA in very low birth weight infants (2013) Early Hum Dev., 89, pp. 175-17

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

Measurement of the top quark mass in the tt→ dilepton channel from √s = 8 TeV ATLAS data

The top quark mass is measured in the tt¯ → dilepton channel (lepton = e,μ) using ATLAS data recorded in the year 2012 at the LHC. The data were taken at a proton proton centre-of-mass energy of √s = 8 TeV and correspond to an integrated luminosity of about 20.2 fb−1. Exploiting the template method, and using the distribution of invariant masses of lepton–b-jet pairs, the top quark mass is measured to be mtop = 172.99±0.41 (stat) ±0.74 (syst) GeV, with a total uncertainty of 0.84 GeV. Finally, a combination with previous ATLAS mtop measurements from √s = 7 TeV data in the tt¯ → dilepton and tt¯ → lepton + jets channels results in mtop = 172.84±0.34 (stat)±0.61 (syst) GeV, with a total uncertainty of 0.70 GeV

Search for TeV-scale gravity signatures in high-mass final states with leptons and jets with the ATLAS detector at sqrt [ s ] = 13TeV

A search for physics beyond the Standard Model, in final states with at least one high transverse momentum charged lepton (electron or muon) and two additional high transverse momentum leptons or jets, is performed using 3.2 fb−1 of proton–proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2015 at √s = 13 TeV. The upper end of the distribution of the scalar sum of the transverse momenta of leptons and jets is sensitive to the production of high-mass objects. No excess of events beyond Standard Model predictions is observed. Exclusion limits are set for models of microscopic black holes with two to six extra dimensions

Search for H→γγ produced in association with top quarks and constraints on the Yukawa coupling between the top quark and the Higgs boson using data taken at 7 TeV and 8 TeV with the ATLAS detector

A search is performed for Higgs bosons produced in association with top quarks using the diphoton decay mode of the Higgs boson. Selection requirements are optimized separately for leptonic and fully hadronic final states from the top quark decays. The dataset used corresponds to an integrated luminosity of 4.5 fb−14.5 fb−1 of proton–proton collisions at a center-of-mass energy of 7 TeV and 20.3 fb−1 at 8 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. No significant excess over the background prediction is observed and upper limits are set on the tt¯H production cross section. The observed exclusion upper limit at 95% confidence level is 6.7 times the predicted Standard Model cross section value. In addition, limits are set on the strength of the Yukawa coupling between the top quark and the Higgs boson, taking into account the dependence of the tt¯H and tH cross sections as well as the H→γγ branching fraction on the Yukawa coupling. Lower and upper limits at 95% confidence level are set at −1.3 and +8.0 times the Yukawa coupling strength in the Standard Model