Abcg2/Bcrp and Abcb1a/Pgp are xenobiotic efflux transporters limiting substrate permeability in the gastrointestinal system and brain, and increasing renal and hepatic drug clearance. The systemic ...impact of Bcrp and Pgp ablation on metabolic homeostasis of endogenous substrates is incompletely understood. We performed untargeted metabolomics of cerebrospinal fluid (CSF) and plasma, transcriptomics of brain, liver and kidney from male Sprague Dawley rats (WT) and Bcrp/Pgp double knock-out (dKO) rats, and integrated metabolomic/transcriptomic analysis to identify putative substrates and perturbations in canonical metabolic pathways. A predictive Bayesian machine learning model was used to predict in silico those metabolites with greater substrate-like features for either transporters. The CSF and plasma levels of 169 metabolites, nutrients, signaling molecules, antioxidants and lipids were significantly altered in dKO rats, compared to WT rats. These metabolite changes suggested alterations in histidine, branched chain amino acid, purine and pyrimidine metabolism in the dKO rats. Levels of methylated and sulfated metabolites and some primary bile acids were increased in dKO CSF or plasma. Elevated uric acid levels appeared to be a primary driver of changes in purine and pyrimidine biosynthesis. Alterations in Bcrp/Pgp dKO CSF levels of antioxidants, precursors of neurotransmitters, and uric acid suggests the transporters may contribute to the regulation of a healthy central nervous system in rats. Microbiome-generated metabolites were found to be elevated in dKO rat plasma and CSF. The altered dKO metabolome appeared to cause compensatory transcriptional change in urate biosynthesis and response to lipopolysaccharide in brain, oxidation-reduction processes and response to oxidative stress and porphyrin biosynthesis in kidney, and circadian rhythm genes in liver. These findings present insight into endogenous functions of Bcrp and Pgp, the impact that transporter substrates, inhibitors or polymorphisms may have on metabolism, how transporter inhibition could rewire drug sensitivity indirectly through metabolic changes, and identify functional Bcrp biomarkers.
Despite improvement during recent decades, extremely preterm infants continue to contribute disproportionately to neonatal mortality and childhood morbidity.
To review survival, in-hospital ...morbidities, care practices, and neurodevelopmental and functional outcomes at 22-26 months' corrected age for extremely preterm infants.
Prospective registry for extremely preterm infants born at 19 US academic centers that are part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. The study included 10 877 infants born at 22-28 weeks' gestational age between January 1, 2013, and December 31, 2018, including 2566 infants born before 27 weeks between January 1, 2013, and December 31, 2016, who completed follow-up assessments at 22-26 months' corrected age. The last assessment was completed on August 13, 2019. Outcomes were compared with a similar cohort of infants born in 2008-2012 adjusting for gestational age.
Extremely preterm birth.
Survival and 12 in-hospital morbidities were assessed, including necrotizing enterocolitis, infection, intracranial hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia. Infants were assessed at 22-26 months' corrected age for 12 health and functional outcomes, including neurodevelopment, cerebral palsy, vision, hearing, rehospitalizations, and need for assistive devices.
The 10 877 infants were 49.0% female and 51.0% male; 78.3% (8495/10848) survived to discharge, an increase from 76.0% in 2008-2012 (adjusted difference, 2.0%; 95% CI, 1.0%-2.9%). Survival to discharge was 10.9% (60/549) for live-born infants at 22 weeks and 94.0% (2267/2412) at 28 weeks. Survival among actively treated infants was 30.0% (60/200) at 22 weeks and 55.8% (535/958) at 23 weeks. All in-hospital morbidities were more likely among infants born at earlier gestational ages. Overall, 8.9% (890/9956) of infants had necrotizing enterocolitis, 2.4% (238/9957) had early-onset infection, 19.9% (1911/9610) had late-onset infection, 14.3% (1386/9705) had severe intracranial hemorrhage, 12.8% (1099/8585) had severe retinopathy of prematurity, and 8.0% (666/8305) had severe bronchopulmonary dysplasia. Among 2930 surviving infants with gestational ages of 22-26 weeks eligible for follow-up, 2566 (87.6%) were examined. By 2-year follow-up, 8.4% (214/2555) of children had moderate to severe cerebral palsy, 1.5% (38/2555) had bilateral blindness, 2.5% (64/2527) required hearing aids or cochlear implants, 49.9% (1277/2561) had been rehospitalized, and 15.4% (393/2560) required mobility aids or other supportive devices. Among 2458 fully evaluated infants, 48.7% (1198/2458) had no or mild neurodevelopmental impairment at follow-up, 29.3% (709/2419) had moderate neurodevelopmental impairment, and 21.2% (512/2419) had severe neurodevelopmental impairment.
Among extremely preterm infants born in 2013-2018 and treated at 19 US academic medical centers, 78.3% survived to discharge, a significantly higher rate than for infants born in 2008-2012. Among infants born at less than 27 weeks' gestational age, rehospitalization and neurodevelopmental impairment were common at 2 years of age.
SNAPSHOT USA is a multicontributor, long‐term camera trap survey designed to survey mammals across the United States. Participants are recruited through community networks and directly through a ...website application (https://www.snapshot-usa.org/). The growing Snapshot dataset is useful, for example, for tracking wildlife population responses to land use, land cover, and climate changes across spatial and temporal scales. Here we present the SNAPSHOT USA 2021 dataset, the third national camera trap survey across the US. Data were collected across 109 camera trap arrays and included 1711 camera sites. The total effort equaled 71,519 camera trap nights and resulted in 172,507 sequences of animal observations. Sampling effort varied among camera trap arrays, with a minimum of 126 camera trap nights, a maximum of 3355 nights, a median 546 nights, and a mean 656 ± 431 nights. This third dataset comprises 51 camera trap arrays that were surveyed during 2019, 2020, and 2021, along with 71 camera trap arrays that were surveyed in 2020 and 2021. All raw data and accompanying metadata are stored on Wildlife Insights (https://www.wildlifeinsights.org/), and are publicly available upon acceptance of the data papers. SNAPSHOT USA aims to sample multiple ecoregions in the United States with adequate representation of each ecoregion according to its relative size. Currently, the relative density of camera trap arrays varies by an order of magnitude for the various ecoregions (0.22–5.9 arrays per 100,000 km2), emphasizing the need to increase sampling effort by further recruiting and retaining contributors. There are no copyright restrictions on these data. We request that authors cite this paper when using these data, or a subset of these data, for publication. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the US Government.
The impact of sea spray aerosols on global climate remains one of the most uncertain components of the aerosol–radiation–climate problem, but has received less attention than the impacts of ...terrestrial and anthropogenic aerosols. The last decade has produced a large body of information regarding the sources and composition of marine aerosols, resulting in a reassessment of the complex role that sea spray particles play in climate and various geophysical phenomena. As sea spray aerosol contributes substantially to the preindustrial, natural background which provides the baseline on top of which anthropogenic forcing should be quantified, and because the ocean covers over 70% of the Earth's surface, the representation of sea spray aerosol in climate models strongly influences the predicted impact on climate of anthropogenic aerosols via direct and indirect effects. In addition, climate change affects atmospheric parameters, such as wind speed which has controlling effect on the production of sea spray aerosol. Recent reviews on sea spray aerosol production and composition (de Leeuw et al., ) summarized the state of the art and remaining uncertainties.Over forty scientists from six countries convened in Raleigh, NC on June 4–6 2012 to review the status and prospects of sea spray aerosol research. Participants were researchers from the oceanography and atmospheric science communities, including academia, private industry, and government agencies. The workshop was held with the primary objectives of (1) identifying the most critical open questions regarding sea spray aerosol and developing a list of priorities for conducting and facilitating novel research and (2) ranking the most pressing science questions based on their feasibility impact on reducing the current uncertainty ranges for different processes. The four main focus groups followed by the three breakout sessions determined the most urgent questions that would improve quantification of sea spray aerosol‐radiation‐climate interactions, with special emphasis on the production flux, number concentrations, chemical composition, nucleation properties, and optical properties.
Over the last two decades, an unprecedented pool of nursing students-many with academic degrees and prior work experience-have entered accelerated programs. This is the first volume to examine core ...issues in accelerated nursing education, such as curriculum innovation, clinical immersion, recruitment and retention of students and faculty, and inter-professional education. It also addresses questions regarding: -How accelerated nursing programs prepare graduates to meet changing health care needs -Which curriculums and clinical models are best suited to accelerated education -What teaching strategies and evidence-based practices ensure high quality results
The synthesis and SAR of a series of 6-(4-(substituted)phenyl)-2-aminopyridines as inhibitors of nitric oxide synthase are described. Compound
3a from this series shows potent and selective ...inhibition of the human nNOS isoform, with pharmacokinetics sufficient to provide in vivo inhibition of nNOS activity.
Best of 2000 Eggers, Dave; Homes, A M; Apraxine, Pierre ...
Artforum international,
12/2000, Volume:
39, Issue:
4
Magazine Article
Twenty-one critics including novelist J. G. Ballard and musician Lou Reed offer their opinions about the year 2000's most influential modern art events.