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Objectives: Following a drug repurposing approach, we aimed to investigate and compare the antibacterial and antibiofilm activities of different classes of phosphate prodrugs (HepDirect, cycloSal, SATE and mix SATE) of antiviral and anticancer FDA-approved nucleoside drugs [zidovudine (AZT), floxouridine (FUDR) and gemcitabine (GEM)] against a variety of pathogenic Gram-positive and -negative bacteria.Methods: Ten prodrugs were synthesized and screened for antibacterial activity against seven Gram-negative and two Gram-positive isolates fully susceptible to traditional antibiotics, alongside six Gram-negative and five Gram-positive isolates with resistance mechanisms. Their ability to prevent and eradicate biofilms of different bacterial pathogens in relation to planktonic growth inhibition was also evaluated, together with their effect on proliferation, viability and apoptosis of different eukaryotic cells.Results: The prodrugs showed decreased antibacterial activity compared with the parent nucleosides. cycloSal-GEM-monophosphate (MP) prodrugs 20a and 20b were the most active agents against Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus) and retained their activity against antibiotic-resistant isolates. cycloSal-FUDR-MP 21a partially retained good activity against the Gram-positive bacteria E. faecalis, Enterococcus faecium and S. aureus. Most of the prodrugs tested displayed very potent preventive antibiofilm specific activity, but not curative. In terms of cytotoxicity, AZT prodrugs did not affect apoptosis or cell viability at the highest concentration tested, and only weak effects on apoptosis and/or cell viability were observed for GEM and FUDR prodrugs.Conclusions: Among the different prodrug approaches, the cycloSal prodrugs appeared the most effective. In particular, cycloSal (17a) and mix SATE (26) AZT prodrugs combine the lowest cytotoxicity with high and broad antibacterial and antibiofilm activity against Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

Background: Preterm children face higher risk of cognitive and academic deficits compared with their full-term peers. The objective of this study was to describe early childhood cognitive ability and kindergarten academic achievement across gestational age at birth in a population-based longitudinal cohort.Methods: The study population included singletons born at 24-42 weeks gestation enrolled in the Early Childhood Longitudinal Study-Birth Cohort (n = 6150 for 2-year outcome, n = 4450 for kindergarten outcome). Home-based assessments measured cognitive ability at 2 years and reading and mathematics achievement at kindergarten age. Linear regression models estimated the association between gestational age and cognitive and academic scores using four different ways of modelling gestational age: continuous variable in linear and quadratic terms; categories for individual weeks; and clinical categories for early preterm, moderate preterm, late preterm, early term, full term, late term, and post-term.Results: Children born at early preterm (24-27 weeks), moderate preterm (28-33 weeks), and late preterm (34-36 weeks) scored significantly worse than full-term (39-40 weeks) peers on 2-year and kindergarten assessments; however, no deficits were observed for early term (37-38 weeks). These categories were a clinically useful and parsimonious approach to stratifying risk of adverse cognitive and academic outcomes.Conclusions: This study estimated the relative performance of children born at 24-42 weeks in a population-based birth cohort using multiple approaches to modelling gestational age, providing a more rigorous understanding of the relationships between the full spectrum of gestational age and cognitive and academic outcomes in early childhood and at school age. [ABSTRACT FROM AUTHOR]

Background: Gestational age estimation by last menstrual period (LMP) vs. ultrasound (or best obstetric estimate in the US) may result in discrepant classification of preterm vs. term birth. We investigated whether such discrepancies are associated with adverse infant outcomes.Methods: We studied singleton livebirths in the Medical Birth Registries of Norway, Sweden and Finland and US live birth certificates from 1999 to the most recent year available. Risk ratios (RR) with 95% confidence intervals (CI) by discordant and concordant gestational age estimation for infant, neonatal and post-neonatal mortality, Apgar score <4 and <7 at 5 min, and neonatal intensive care unit (NICU) admission were estimated using generalised linear models, adjusting for maternal age, education, parity, year of birth, and infant sex. Results were presented stratified by country.Results: Compared to infants born at term by both methods, infants born preterm by ultrasound/best obstetric estimate but term by LMP had higher infant mortality risks (range of adjusted RRs 3.9 to 7.2) and modestly higher risks were obtained among infants born preterm by LMP but term by ultrasound/best obstetric estimate (range of adjusted RRs 1.6 to 1.9). Risk estimates for the other outcomes showed the same pattern. These findings were consistent across all four countries.Conclusions: Infants classified as preterm by ultrasound/best estimate, but term by LMP have consistently higher risks of adverse outcomes than those classified as preterm by LMP but term by ultrasound/best estimate. Compared with ultrasound/best estimate, use of LMP overestimates the proportion of births that are preterm. [ABSTRACT FROM AUTHOR]