Abstract Background Preeclampsia is a pregnancy-specific disorder that remains a leading cause of maternal, fetal and neonatal morbidity and mortality, and is associated with risk for future ...cardiovascular disease. There are no reliable predictors, specific preventative measures or treatments other than delivery. A widely held view is that the antecedents of preeclampsia lie with impaired placentation in early pregnancy. Accordingly, we hypothesized dysregulation of global gene expression in first trimester placentas of women who later manifested preeclampsia. Methods Surplus chorionic villus sampling (CVS) tissues were collected at 10–12 weeks gestation in 160 patients with singleton fetuses. Four patients developed preeclampsia, and their banked CVS specimens were matched to 8 control samples from patients with unaffected pregnancies. Affymetrix HG-U133 Plus 2.0 GeneChips were utilized for microarray analysis. Naïve Bayes prediction modeling and pathway analysis were conducted. qRT-PCR examined three of the dysregulated genes. Results Thirty-six differentially expressed genes were identified in the preeclampsia placentas. qRT-PCR verified the microarray analysis. Thirty-one genes were down-regulated. Many were related to inflammation/immunoregulation and cell motility. Decidual gene dysregulation was prominent. No evidence was found for alterations in hypoxia and oxidative stress regulated genes. Conclusions To our knowledge, this is the first study to show dysregulation of gene expression in the early placentas of women ∼6 months before developing preeclampsia, thereby reinforcing a placental origin of the disorder. We hypothesize that placentation in preeclampsia is compromised in the first trimester by maternal and fetal immune dysregulation, abnormal decidualization, or both, thereby impairing trophoblast invasion. Several of the genes provide potential targets for the development of clinical biomarkers in maternal blood during the first trimester. Supplementary materials are available for this article via the publisher's online edition.
Over the past two decades, ultrasound (US) has become widely accepted to guide safe and accurate insertion of vascular devices in critically ill patients. We emphasize central venous catheter ...insertion, given its broad application in critically ill patients, but also review the use of US for accessing peripheral veins, arteries, the medullary canal, and vessels for institution of extracorporeal life support. To ensure procedural safety and high cannulation success rates we recommend using a systematic protocolized approach for US-guided vascular access in elective clinical situations. A standardized approach minimizes variability in clinical practice, provides a framework for education and training, facilitates implementation, and enables quality analysis. This review will address the state of US-guided vascular access, including current practice and future directions.
Extracorporeal life support (ECLS) was developed more than 50 years ago, initially with venoarterial and subsequently with venovenous configurations. As the technique of ECLS significantly improved ...and newer skills developed, complexity in terminology and advances in cannula design led to some misunderstanding of and inconsistency in definitions, both in clinical practice and in scientific research. This document is a consensus of multispecialty international representatives of the Extracorporeal Life Support Organization, including the North America, Latin America, EuroELSO, South West Asia and Africa, and Asia-Pacific chapters, imparting a global perspective on ECLS. The goal is to provide a consistent and unambiguous nomenclature for ECLS and to overcome the inconsistent use of abbreviations for ECLS cannulation. Secondary benefits are ease of multicenter collaboration in research, improved registry data quality, and clear communication among practitioners and researchers in the field.
Activation of the c-Met pathway occurs in a range of malignancies, including papillary renal cell carcinoma (RCC). Its activity in clear cell RCC is less clear. We investigated c-Met expression and ...inhibition in a large cohort of RCC tumors and cell lines.
c-Met protein expression was determined by automated quantitative analysis (AQUA) on a tissue microarray (TMA) constructed from 330 RCC tumors paired with adjacent normal renal tissue. c-Met expression and selective inhibition with SU11274 and ARQ 197 were studied in clear cell RCC cell lines.
Higher c-Met expression was detected in all RCC subtypes than in the adjacent normal renal tissue (P < 0.0001). Expression was highest in papillary and sarcomatoid subtypes, and high-grade and stage tumors. Higher c-Met expression correlated with worse disease-specific survival risk ratio = 1.36; 95% confidence interval (CI) 1.08–1.74; P = 0.0091 and was an independent predictor of survival, maintained in clear cell subset analyses. c-Met protein was activated in all cell lines, and proliferation (and colony formation) was blocked by SU11274 and ARQ 197.
c-Met is associated with poor pathologic features and prognosis in RCC. c-Met inhibition demonstrates in vitro activity against clear cell RCC. Further study of ARQ 197 with appropriate biomarker studies in RCC is warranted.
Classical linguistic theory assumes that formal aspects, like sound, are not internally related to the meaning of words. However, recent research suggests language might code affective meaning such ...as threat and alert sublexically. Positing affective phonological iconicity as a systematic organization principle of the German lexicon, we calculated sublexical affective values for sub-syllabic phonological word segments from a large-scale affective lexical German database by averaging valence and arousal ratings of all words any phonological segment appears in. We tested word stimuli with either consistent or inconsistent mappings between lexical affective meaning and sublexical affective values (negative-valence/high-arousal vs. neutral-valence/low-arousal) in an EEG visual-lexical-decision task. A mismatch between sublexical and lexical affective values elicited an increased N400 response. These results reveal that systematic affective phonological iconicity – extracted from the lexicon - impacts the extraction of lexical word meaning during reading.
Nitrogen loss via overland flow from agricultural land use is a global threat to waterways. On-farm denitrifying woodchip bioreactors can mitigate NO3− exports by increasing denitrification capacity. ...However, denitrification in sub-optimal conditions releases the greenhouse gas nitrous oxide (N2O), swapping the pollution from aquatic to atmospheric reservoirs. Here, we assess NO3−-N removal and N2O emissions from a new edge-of-field surface-flow bioreactor during ten rain events on intensive farming land. Nitrate removal rates (NRR) varied between 5.4 and 76.2 g NO3−-N m−3 wetted woodchip d−1 with a mean of 30.3 ± 7.3 g NO3−-N m−3. The nitrate removal efficiency (NRE) was ∼73% in ideal hydrological conditions and ∼18% in non-ideal conditions. The fraction of NO3−-N converted to N2O (rN2O) in the bioreactor was ∼3.3 fold lower than the expected 0.75% IPCC emission factor. We update the global bioreactor estimated Q10 (NRR increase every 10 °C) from a recent meta-analysis with previously unavailable data to >20 °C, yielding a new global Q10 factor of 3.1. Mean N2O CO2-eq emissions (431.9 ± 125.4 g CO2-eq emissions day−1) indicate that the bioreactor was not significantly swapping aquatic NO3− for N2O pollution. Our estimated NO3−-N removal from the bioreactor (9.9 kg NO3−-N ha−1 yr−1) costs US$13.14 per kg NO3−-N removed and represents ∼30% NO3−-N removal when incorporating all flow and overflow events. Overall, edge-of-field surface-flow bioreactors seem to be a cost-effective solution to reduce NO3−-N runoff with minor pollution swapping to N2O.
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•A novel edge-of-field surface-flow bioreactor reduced agricultural NO3−-N runoff by ∼18–∼73%.•The bioreactor did not contribute significantly to N2O emissions.•The estimated cost of removal is ∼US$13 for each kg NO3−-N attenuated.•Surface-flow bioreactors can be effective in systems dominated by surface runoff.
The landforms of northern Gale crater on Mars expose thick sequences of sedimentary rocks. Based on images obtained by the Curiosity rover, we interpret these outcrops as evidence for past fluvial, ...deltaic, and lacustrine environments. Degradation of the crater wall and rim probably supplied these sediments, which advanced inward from the wall, infilling both the crater and an internal lake basin to a thickness of at least 75 meters. This intracrater lake system probably existed intermittently for thousands to millions of years, implying a relatively wet climate that supplied moisture to the crater rim and transported sediment via streams into the lake basin. The deposits in Gale crater were then exhumed, probably by wind-driven erosion, creating Aeolis Mons (Mount Sharp).
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