Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants

BACKGROUND: Preterm infants with respiratory distress syndrome (RDS) given inositol had reduced bronchopulmonary dysplasia (BPD), death and severe retinopathy of prematurity (ROP). We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization. METHODS: Infants ≤ 29 wk GA (n = 122, 14 centers) were randomized and treated with placebo or inositol at 10, 40, or 80 mg/kg/d. Intravenous administration converted to enteral when feedings were established, and continued to the first of 10 wk, 34 wk postmenstrual age (PMA) or discharge. Serum collection employed a sparse sampling population pharmacokinetics design. Inositol urine losses and feeding intakes were measured. Safety was prospectively monitored. RESULTS: At 80 mg/kg/d mean serum levels reached 140 mg/l, similar to Hallman's findings. Levels declined after 2 wk, converging in all groups by 6 wk. Analyses showed a mean volume of distribution 0.657 l/kg, clearance 0.058 l/kg/h, and half-life 7.90 h. Adverse events and comorbidities were fewer in the inositol groups, but not significantly so. CONCLUSION: Multiple dose inositol at 80 mg/kg/d was not associated with increased adverse events, achieves previously effective serum levels, and is appropriate for investigation in a phase III trial

Blood myo-inositol concentrations in preterm and term infants

Objective: To describe relationship between cord blood (representing fetal) myo-inositol concentrations and gestational age (GA) and to determine trends of blood concentrations in enterally and parenterally fed infants from birth to 70 days of age. Design/methods: Samples were collected in 281 fed or unfed infants born in 2005 and 2006. Myo-inositol concentrations were displayed in scatter plots and analyzed with linear regression models of natural log-transformed values. Results: In 441 samples obtained from 281 infants, myo-inositol concentrations varied from nondetectable to 1494 μmol/L. Cord myo-inositol concentrations decreased an estimated 11.9% per week increase in GA. Postnatal myo-inositol concentrations decreased an estimated 14.3% per week increase in postmenstrual age (PMA) and were higher for enterally fed infants compared to unfed infants (51% increase for fed vs. unfed infants). Conclusions: Fetal myo-inositol concentrations decreased with increasing GA. Postnatal concentrations decreased with increasing PMA and were higher among enterally fed than unfed infants

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Camioneta Mágica: Developing a Mobile Education Workshop to Reconnect Costa Rican Youth with Their Environment

Children within the city of San José, Costa Rica lack access to greenspaces and are often disconnected from the rich natural environment. This project aided Árboles Mágicos to model and determine the feasibility of a mobile nature workshop that would teach children in San José about Costa Rican trees and forests. We completed a literature review and interviewed teachers and museum exhibit designers to identify effective teaching methods and determine the educational content of the workshop. We suggested the workshop teach skills and values such as empathy and transversality through environmental topics and by using interactive and autonomous activities. We created two designs of the mobile nature workshop, including the vehicle and the activities, and assessed their cost and feasibility

Data Series 902 Digital Geospatial Presentation of Geoelectrical and Geotechnical Data for the Lower American River and Flood Plain, East Sacramento, California Digital Geospatial Presentation of Geoelectrical and Geotechnical Data for the Lower American

For more information on the USGS-the Federal source for science about the Earth, its natural and living resources, natural hazards, and the environment, visit http://www.usgs.gov or call 1-888-ASK-USGS. For an overview of USGS information products, including maps, imagery, and publications, visit http://www.usgs.gov/pubprod To order this and other USGS information products, visit http://store.usgs.gov Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government. Although this information product, for the most part, is in the public domain, it also may contain copyrighted materials as noted in the text. Permission to reproduce copyrighted items must be secured from the copyright owner. Abstract To characterize the extent and thickness of lithologic units that may have differing scour potential, the U.S. Geological Survey, in cooperation with the U.S. Army Corps of Engineers, has performed several geoelectrical surveys of the lower American River channel and flood plain between Cal Expo and the Rio Americano High School in east Sacramento, California. Additional geotechnical data have been collected by the U.S. Army Corps of Engineers and its contractors. Data resulting from these surveys have been compiled into similar database formats and converted to uniform geospatial datums and projections. These data have been visualized in a digital three-dimensional framework project that can be viewed using freely available software. These data facilitate a comprehensive analysis of the resistivity structure underlying the lower American River corridor and assist in levee system management

Anti-HIV-1 activity of elafin depends on its nuclear localization and altered innate immune activation in female genital epithelial cells.

Elafin (E) and its precursor trappin-2 (Tr) are alarm antiproteases with antimicrobial and immunomodulatory activities. Tr and E (Tr/E) have been associated with HIV-1 resistance. We recently showed that Tr/E reduced IL-8 secretion and NF-κB activation in response to a mimic of viral dsRNA and contributed to anti-HIV activity of cervicovaginal lavage fluid (CVL) of HIV-resistant (HIV-R) commercial sex workers (CSWs). Additionally, Tr, and more so E, were found to inhibit attachment/entry and transcytosis of HIV-1 in human endometrial HEC-1A cells, acting through virus or cells. Given their immunomodulatory activity, we hypothesized that Tr/E could exert anti-HIV-1 activity at multiple levels. Here, using tagged and untagged Tr/E proteins, we comparatively evaluated their protease inhibitory, anti-HIV-1, and immunomodulatory activities, and cellular distribution. E appeared to function as an autocrine/paracrine factor in HEC-1A cells, and anti-HIV-1 activity of E depended on its unmodified N-terminus and altered cellular innate activation, but not its antiprotease activity. Specifically, exogenously added N-terminus-unmodified E was able to enter the nucleus and to reduce viral attachment/entry and transcytosis, preferentially affecting R5-HIV-1(ADA), but not X4-HIV-1(IIIB). Further, anti-HIV-1 activity of E was associated with significantly decreased HIV-1-triggered IL-8 release, attenuated NF-κB/p65 nuclear translocation, and significantly modulated mRNA expression of innate sensors TLR3 and RIG-I in HEC-1A cells. Most importantly, we found that elevated Tr/E in CVLs of HIV-R CSWs were associated with lower mRNA levels of TLRs 2, 3, 4 and RIG-I in the genital ECs from this cohort, suggesting a link between Tr/E, HIV-1 resistance and modulated innate viral recognition in the female genital mucosa. Collectively, our data indicate that unmodified N-terminus is critical for intranuclear localization and anti-HIV-1 activity of E. We also propose that E-mediated altered cellular innate activation most likely contributes to the HIV-R phenotype of these subjects

Cellular localization of exogenous elafin in genital epithelial cells.

<p>Immunofluorescence staining of cellular distribution of 1 µg/ml of human Tr or E (green) proteins, detected using TRAB2O (<i>A,B,C</i>), His-tag- (<i>D,E,F</i>), and HAT-tag-specific antibodies (<i>G,H</i>). Nuclei were visualized with propidium iodide (PI) as red. Representative staining of three different experiments is shown for Tr or E proteins at 1 h post exposure and merged image shows human Tr or E visualized as yellow in composite panels. Scale bar, 20 mm.</p

Genital ECs from HIV-resistant (HIV-R) commercial sex workers (CSWs) have significantly lower mRNA expression of TLR2, TLR4, and RIG-I.

<p>Relative mRNA expression levels of TLR2, TLR4, and RIG-I in cervical ECs of HIV-S (▪, N = 10) and HIV-R (•, N = 10) were assessed by RT-qPCR. The relative quantity of expression of these genes was normalized against 18S. The data are shown as the mean ± SD. Statistical analysis was performed using ANOVA, with p considered significant when p<0.05.</p