Identification of diagnostic biomarkers for infection in premature neonates

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.

Maternal breastfeeding in Portugal: factors associated with the duration and premature cessation

Tese de mestrado em Bioestatística, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2013

Suivi neurodéveloppemental de l'enfant né prématuré dans l'Arc lémanique [Neurodevelopmental follow-up of premature children in Lausanne and Geneva].

Preterm children born before 32 weeks of gestation represent 1% of the annual births in Switzerland, and are the most at risk of neurodevelopmental disabilities. A neurological surveillance is thus implemented in the neonatal units, and multidisciplinary neurodevelopmental follow-up is offered to all our preterm patients. The follow-up clinics of the University hospitals in Lausanne and Geneva follow the Swiss guidelines for follow-up. An extended history and neurological examination is taken at each appointment, and a standardized test of development is performed. These examinations, which take place between the ages of 3 months and 9 years old, allow the early identification and treatment of developmental disorders frequent in this population, such as motor, cognitive or behavioral disorders, as well as the monitoring of the quality of neonatal care.

16q24.1 microdeletion in a premature newborn: Usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn.

OBJECTIVE:: Report of a 16q24.1 deletion in a premature newborn, demonstrating the usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn and multiple congenital malformations. DESIGN:: Descriptive case report. SETTING:: Genetic department and neonatal intensive care unit of a tertiary care children's hospital. INTERVENTIONS:: None. PATIENT:: We report the case of a preterm male infant, born at 26 wks of gestation. A cardiac malformation and bilateral hydronephrosis were diagnosed at 19 wks of gestation. Karyotype analysis was normal, and a 22q11.2 microdeletion was excluded by fluorescence in situ hybridization analysis. A cesarean section was performed due to fetal distress. The patient developed persistent pulmonary hypertension unresponsive to mechanical ventilation and nitric oxide treatment and expired at 16 hrs of life. MEASUREMENTS AND MAIN RESULTS:: An autopsy revealed partial atrioventricular canal malformation and showed bilateral dilation of the renal pelvocaliceal system with bilateral ureteral stenosis and annular pancreas. Array-based comparative genomic hybridization analysis (Agilent oligoNT 44K, Agilent Technologies, Santa Clara, CA) showed an interstitial microdeletion encompassing the forkhead box gene cluster in 16q24.1. Review of the pulmonary microscopic examination showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins. Some features were less prominent due to the gestational age. CONCLUSIONS:: Our review of the literature shows that alveolar capillary dysplasia with misalignment of pulmonary veins is rare but probably underreported. Prematurity is not a usual presentation, and histologic features are difficult to interpret. In our case, array-based comparative genomic hybridization revealed a 16q24.1 deletion, leading to the final diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins. It emphasizes the usefulness of array-based comparative genomic hybridization analysis as a diagnostic tool with implications for both prognosis and management decisions in newborns with refractory persistent pulmonary hypertension and multiple congenital malformations.

Treatment of genital mycoplasma in colonized pregnant women in late pregnancy is associated with a lower rate of premature labour and neonatal complications.

Mycoplasma hominis and Ureaplasma spp. may colonize the human genital tract and have been associated with adverse pregnancy outcomes such as preterm labour and preterm premature rupture of membranes. However, as these bacteria can reside in the normal vaginal flora, there are controversies regarding their true role during pregnancy and so the need to treat these organisms. We therefore conducted a retrospective analysis to evaluate the treatment of genital mycoplasma in 5377 pregnant patients showing symptoms of potential obstetric complications at 25-37 weeks of gestation. Women presenting with symptoms were routinely screened by culture for the presence of these bacteria and treated with clindamycin when positive. Compared with uninfected untreated patients, women treated for genital mycoplasma demonstrated lower rates of premature labour. Indeed preterm birth rates were, respectively, 40.9% and 37.7% in women colonized with Ureaplasma spp. and M. hominis, compared with 44.1% in uncolonized women (Ureaplasma spp., p 0.024; M. hominis, p 0.001). Moreover, a reduction of neonatal complications rates was observed, with 10.9% of newborns developing respiratory diseases in case of Ureaplasma spp. colonization and 5.9% in the presence of M. hominis, compared with 12.8% in the absence of those bacteria (Ureaplasma spp., p 0.050; M. hominis, p <0.001). Microbiological screening of Ureaplasma spp. and/or M. hominis and pre-emptive antibiotic therapy of symptomatic pregnant women in late pregnancy might represent a beneficial strategy to reduce premature labour and neonatal complications.

The moral difference between premature infants and neonates compared to older patients

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Psychometric properties of the d2 selective attention test in a sample of premature and born-at-term babies. 'Caracter??sticas psicom??tricas del test de atenci??n selectiva d2 en ni??os prematuros y nacidos a termino''

Resumen tomado de la publicaci??n. Resumen tambi??n en ingl??s

"Genome-Wide Linkage in a Highly Consanguineous Pedigree Reveals Two Novel Loci on Chromosome 7 for Non-Syndromic Familial Premature Ovarian Failure"

Background: The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10–15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients. Methodology/Principal Findings: We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LODmax of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations. Conclusions/Significance: We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function.

It is premature to include non-CO2 effects of aviation in emission trading schemes

The recent G8 Gleneagles climate statement signed on 8 July 2005 specifically mentions a determination to lessen the impact of aviation on climate [Gleneagles, 2005. The Gleneagles communique: climate change, energy and sustainable development. http://www.fco.gov.uk/Files/kfile/PostG8_Gleneagles_Communique.pdf]. In January 2005 the European Union Emission Trading Scheme (ETS) commenced operation as the largest multi-country, multi-sector ETS in the world, albeit currently limited only to CO2 emissions. At present the scheme makes no provision for aircraft emissions. However, the UK Government would like to see aircraft included in the ETS and plans to use its Presidencies of both the EU and G8 in 2005 to implement these schemes within the EU and perhaps internationally. Non-CO2 effects have been included in some policy-orientated studies of the impact of aviation but we argue that the inclusion of such effects in any such ETS scheme is premature; we specifically argue that use of the Radiative Forcing Index for comparing emissions from different sources is inappropriate and that there is currently no metric for such a purpose that is likely to enable their inclusion in the near future. (c) 2005 Elsevier Ltd. All rights reserved.

Premature impairment of methylation pathway and cardiac metabolic dysfunction in fa/fa obese Zucker rats

Increasing evidence suggests that obesity is a chronic inflammatory disease, in which adipose tissue is involved in a network of endocrine signals to modulate energy homeostasis. These oxidative-inflammatory pathways, which are associated with cardiovascular complications, are also observed during the aging process. In this study, we investigated the interaction between aging and the development of obesity in a hyperphagic rat model. Metabolic profiles of the liver, white adipose tissue (WAT) and heart from young and adult Zucker lean (fa/+) and obese (fa/fa) rats were characterized using a (1)H NMR-based metabonomics approach. We observed premature metabolic modifications in all studied organs in obese animals, some of which were comparable to those observed in adult lean animals. In the cardiac tissue, young obese rats displayed lower lactate and scyllo-inositol levels associated with higher creatine, choline and phosphocholine levels, indicating an early modulation of energy and membrane metabolism. An early alteration of the hepatic methylation and transsulfuration pathways in both groups of obese rats indicated that these pathways were affected before diabetic onset. These findings therefore support the hypothesis that obesity parallels some metabolic perturbations observed in the aging process and provides new insights into the metabolic modifications occurring in pre-diabetic state.

Convergence and accommodation development is pre-programmed in premature infants

Purpose This study investigated whether vergence and accommodation development in pre-term infants is pre-programmed or is driven by experience. Methods 32 healthy infants, born at mean 34 weeks gestation (range 31.2-36 weeks) were compared with 45 healthy full-term infants (mean 40.0 weeks) over a 6 month period, starting at 4-6 weeks post-natally. Simultaneous accommodation and convergence to a detailed target were measured using a Plusoptix PowerRefII infra-red photorefractor as a target moved between 0.33m and 2m. Stimulus/response gains and responses at 0.33m and 2m were compared by both corrected (gestational) age and chronological (post-natal) age. Results When compared by their corrected age, pre-term and full-term infants showed few significant differences in vergence and accommodation responses after 6-7 weeks of age. However, when compared by chronological age, pre-term infants’ responses were more variable, with significantly reduced vergence gains, reduced vergence response at 0.33m, reduced accommodation gain, and increased accommodation at 2m, compared to full-term infants between 8-13 weeks after birth. Conclusions When matched by corrected age, vergence and accommodation in pre-term infants show few differences from full-term infants’ responses. Maturation appears pre-programmed and is not advanced by visual experience. Longer periods of immature visual responses might leave pre-term infants more at risk of development of oculomotor deficits such as strabismus.  

Premature germination of resting spores as a means of Protecting brassica crops from Plasmodiophora brassicae Wor., (clubroot)

Premature germination of resting spores as a means of protecting brassica crops from Plasmodiphora brassicae Wor., (Clubroot). Crop Protection. Clubroot disease causes substantial yield and quality losses in broadacre oil seed and intensive vegetable brassica crops worldwide. The causal microbe Plasmodiophora brassicae Wor., perennates as soil-borne dormant resting spores. Their germination is triggered by exudates from host roots. A valuable addition to sustainable integrated control strategies could be developed by identifying and synthesising the molecules responsible for stimulating resting spore germination. This paper reports experiments in which stimulatory exudates were collected from brassica roots following exposure to infective stages of P. brassicae. Analyses identified a germination signalling molecule of circa 1 kDa formed of glucose sub-units. Mass spectral analyses showed this to be a complex hexasaccharide carbohydrate with structural similarities to the components of plant cell walls. This is the first report of a host generated hexasaccharide which is capable of stimulating the germination of resting spores of P. brassicae. The implications for environmentally benign control of clubroot are discussed briefly.