Pyrazolo[1,5-a]-1,3,5-triazine C-Nucleoside as Deoxyadenosine Analogue: Synthesis, Pairing, and Resistance to Hydrolysis

International audienceThe synthesis of a pyrazolo[1,5-a]-1,3,5-triazine C-nucleoside (dAPT), designed to form two hydrogen bonds with a complementary dT residue, is reported. Oligonucleotides including this dA nucleoside analogue possess base-pairing properties similar to those of the parent oligonucleotide. This dA nucleoside analogue is more resistant to acid-catalyzed hydrolysis than dA

Synthesis and properties of 2′-O-neopentyl modified oligonucleotides

International audienc

Pyrazolo[1,5‑<i>a</i>]‑1,3,5-triazine C‑Nucleoside as Deoxyadenosine Analogue: Synthesis, Pairing, and Resistance to Hydrolysis

The synthesis of a pyrazolo­[1,5-<i>a</i>]-1,3,5-triazine C<b>-</b>nucleoside (dA^PT), designed to form two hydrogen bonds with a complementary dT residue, is reported. Oligonucleotides including this dA nucleoside analogue possess base-pairing properties similar to those of the parent oligonucleotide. This dA nucleoside analogue is more resistant to acid-catalyzed hydrolysis than dA

Brain injury in very preterm children and neurosensory and cognitive disabilities during childhood: the EPIPAGE cohort study.

OBJECTIVE: To investigate the association of motor and cognitive/learning deficiencies and overall disabilities in very preterm (VPT) children and their relations to gestational age (GA) and brain lesions. DESIGN SETTING AND PARTICIPANTS: EPIPAGE is a longitudinal population-based cohort study of children born before 33 weeks' gestation (WG) in 9 French regions in 1997-1998. Cumulating data from all follow up stages, neurodevelopmental outcomes were available for 90% of the 2480 VPT survivors at 8 years. Main outcomes were association of motor and cognitive deficiencies and existence of at least one deficiency (motor, cognitive, behavioral/psychiatric, epileptic, visual, and/or hearing deficiencies) in three GA groups (24-26, 27-28, and 29-32WG) and four groups of brain lesions (none, minor, moderate, or severe). RESULTS: VPT had high rates of motor (14%) and cognitive (31%) deficiencies. Only 6% had an isolated motor deficiency, 23% an isolated cognitive one and 8% both types. This rate reached 20% among extremely preterm. Psychiatric disorders and epilepsy were observed in 6% and 2% of children, respectively. The risks of at least one severe or moderate deficiency were 11 and 29%. These risks increased as GA decreased; only 36% of children born extremely preterm had no reported deficiency. Among children with major white matter injury (WMI), deficiency rates reached 71% at 24-26WG, 88% at 27-28WG, and 80% at 29-32WG; more than 40% had associated motor and cognitive deficiencies. By contrast, isolated cognitive deficiency was the most frequent problem among children without major lesions. CONCLUSIONS: In VPT, the lower the GA, the higher the neurodisability rate. Cerebral palsy is common. Impaired cognitive development is more frequent. Its occurrence in case without WMI or early motor disorders makes long-term follow up necessary. The strong association between motor impairments, when they exist, and later cognitive dysfunction supports the hypothesis of a common origin of these difficulties

A Novel Strategy for Human Papillomavirus Detection and Genotyping with SybrGreen and Molecular Beacon Polymerase Chain Reaction

Human papillomaviruses (HPVs) play an important role in the pathogenesis of cervical cancer. For identification of the large number of different HPV types found in (pre)malignant lesions, a robust methodology is needed that combines general HPV detection with HPV genotyping. We have developed for formaldehyde-fixed samples a strategy that, in a homogenous, real-time fluorescence polymerase chain reaction (PCR)-based assay, accomplishes general HPV detection by SybrGreen reporting of HPV-DNA amplicons, and genotyping of seven prevalent HPV types (HPV-6, -11, -16, -18, -31, -33, -45) by real-time molecular beacon PCR. The false-positive rate of the HPV SybrGreen-PCR was 4%, making it well suited as a prescreening, general HPV detection technology. The type specificity of the seven selected HPV molecular beacons was 100% and double infections were readily identified. The multiplexing capacity of the HPV molecular beacon PCR was analyzed and up to three differently labeled molecular beacons could be used in one PCR reaction without observing cross talk. The inherent quantitation capacities of real-time fluorescence PCR allowed the determination of average HPV copy number per cell. We conclude that the HPV SybrGreen-PCR in combination with the HPV molecular beacon PCR provides a robust, sensitive, and quantitative general HPV detection and genotyping methodology

Volume of neonatal care and survival without disability at 2 years in very preterm infants: results of a french national cohort study.

International audienceObjectives To investigate the relation between neonatal intensive care unit (NICU) volume and survival, and neuromotor and sensory disabilities at 2 years in very preterm infants. Study design The EPIPAGE-2 (Etude Epidémiologique sur les Petits Âges Gestationnels-2) national prospective population-based cohort study was used to include 2447 babies born alive in 66 level III hospitals between 24 and 30 completed weeks of gestation in 2011. The outcome was survival without disabilities (levels 2-5 of the Gross Motor Function Classification System for cerebral palsy with or without unilateral or bilateral blindness or deafness). Units were grouped in quartiles according to volume, defined as the annual admissions of very preterm babies. Multivariate logistic regression analyses with population average models were used. Results Survival at discharge was lower in hospitals with lower volumes of neonatal activity (aOR 0.55, 95% CI 0.33-0.91). Survival without neuromotor and sensory disabilities at 2 years increased with hospital volume, from 75% to 80.7% in the highest volume units. After adjustment for gestational age, small for gestational age, sex, maternal age, infertility treatment, multiple pregnancy, principal cause of prematurity, parental socioeconomic status, and mother's country of birth, survival without neuromotor or sensory disabilities was significantly lower in hospitals with a lower volume of neonatal activity (aOR 0.60, 95% CI 0.38-0.95) than in the highest quartile hospitals. Conclusions These results suggest that lower neonatal intensive care unit volume is associated with lower survival without an increase in disabilities at 2 years. These results could be useful to generate improvements of perinatal regionalization

Early extubation is not associated with severe intraventricular hemorrhage in preterm infants born before 29 weeks of gestation. Results of an EPIPAGE-2 cohort study.

ObjectiveTo determine whether there is an association between severe intraventricular hemorrhage and early extubation in preterm infants born before 29 weeks of gestational age and intubated at birth.MethodsThis study included 1587 preterm infants from a nationwide French population cohort (EPIPAGE-2). Secondary data on intubated preterm infants were analyzed. After gestational age and propensity score matching (1:1) we built two comparable groups: an early extubation group and a delayed extubation group. Each neonate in one group was paired with a neonate in the other group having the same propensity score and gestational age. Early extubation was defined as extubation within 48 hours of life. Severe intraventricular hemorrhages were defined as grade III or IV hemorrhages according to the Papile classification.ResultsAfter matching, there were 398 neonates in each group. Using a generalized estimating equation model, we found that intraventricular hemorrhage was not associated with early extubation (adjusted OR 0.9, 95%CI 0.6-1.4). This result was supported by sensitivity analyses.ConclusionThe practice of early extubation was not associated with an increased proportion of intraventricular hemorrhages. To complete these results, the long-term neurologic outcomes of these infants need to be assessed

Neonatal infection and 5-year neurodevelopmental outcome of very preterm infants.

International audienceOBJECTIVE: To determine whether neonatal infections are associated with a higher risk of adverse neurodevelopment at 5 years of age in a population-based cohort of very preterm children. METHODS: We included all live births between 22 and 32 weeks of gestation, from 9 regions in France, in 1997 (EPIPAGE study). Of the 2665 live births, 2277 were eligible for a follow-up evaluation at 5 years of age: 1769 had a medical examination and 1495 underwent cognitive assessment. Cerebral palsy and cognitive impairment were studied as a function of early-onset sepsis (EOS) and late-onset sepsis (LOS), after adjustment for potential confounding factors, in multivariate logistic regression models. RESULTS: A total of 139 (5%) of the 2665 live births included in the study presented with EOS alone (without associated LOS), 752 (28%) had LOS alone (without associated EOS), and 64 (2%) displayed both EOS and LOS. At 5 years of age, the frequency of cerebral palsy was 9% (157 of 1769) and that of cognitive impairment was 12% (177 of 1495). The frequency of cerebral palsy was higher in infants with isolated EOS (odds ratio [OR]: 1.70 [95% confidence interval (CI): 0.84-3.45]) or isolated LOS (OR: 1.71 [95% CI: 1.14-2.56]) than in uninfected infants, and this risk was even higher in cases of combined EOS and LOS (OR: 2.33 [95% CI: 1.02-5.33]). There was no association between neonatal infection and cognitive impairment. CONCLUSIONS: Neonatal infections in these very preterm infants were associated with a higher risk of cerebral palsy at the age of 5 years, particularly in infants presenting with both EOS and LOS

Deficiencies according to gestational age and neonatal cerebral lesions.

(1)<p>inclusion 1997+1998.</p>(2)<p>inclusion 1997.</p>(3)<p>Major : cystic PVL or IPH, Moderate : persistent echodensities or ventricular dilatation or grade III IVH, Minor : grade II and grade I IVH (1 missing neonatal cerebral lesion information in the group of 24–26 SA and 32 missing in the groups 29–32 SA).</p