218 research outputs found

    Analysing EHR navigation patterns and digital workflows among physicians during ICU pre-rounds

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    Background: Some physicians in intensive care units (ICUs) report that electronic health records (EHRs) can be cumbersome and disruptive to workflow. There are significant gaps in our understanding of the physician–EHR interaction. Objective: To better understand how clinicians use the EHR for chart review during ICU pre-rounds through the characterisation and description of screen navigation pathways and workflow patterns. Method: We conducted a live, direct observational study of six physician trainees performing electronic chart review during daily pre-rounds in the 30-bed medical ICU at a large academic medical centre in the Southeastern United States. A tailored checklist was used by observers for data collection. Results: We observed 52 distinct live patient chart review encounters, capturing a total of 2.7 hours of pre-rounding chart review activity by six individual physicians. Physicians reviewed an average of 8.7 patients (range = 5–12), spending a mean of 3:05 minutes per patient (range = 1:34–5:18). On average, physicians visited 6.3 (±3.1) total EHR screens per patient (range = 1–16). Four unique screens were viewed most commonly, accounting for over half (52.7%) of all screen visits: results review (17.9%), summary/overview (13.0%), flowsheet (12.7%), and the chart review tab (9.1%). Navigation pathways were highly variable, but several common screen transition patterns emerged across users. Average interrater reliability for the paired EHR observation was 80.0%. Conclusion: We observed the physician–EHR interaction during ICU pre-rounds to be brief and highly focused. Although we observed a high degree of “information sprawl” in physicians’ digital navigation, we also identified common launch points for electronic chart review, key high-traffic screens and common screen transition patterns. Implications: From the study findings, we suggest recommendations towards improved EHR design

    In utero exposure to transient ischemia-hypoxemia promotes long-term neurodevelopmental abnormalities in male rat offspring

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    The impact of transient ischemic-hypoxemic insults on the developing fetal brain is poorly understood despite evidence suggesting an association with neurodevelopmental disorders such as schizophrenia and autism. To address this, we designed an aberrant uterine hypercontractility paradigm with oxytocin to better assess the consequences of acute, but transient, placental ischemia-hypoxemia in term pregnant rats. Using MRI, we confirmed that oxytocin-induced aberrant uterine hypercontractility substantially compromised uteroplacental perfusion. This was supported by the observation of oxidative stress and increased lactate concentration in the fetal brain. Genes related to oxidative stress pathways were significantly upregulated in male, but not female, offspring 1 hour after oxytocin-induced placental ischemia-hypoxemia. Persistent upregulation of select mitochondrial electron transport chain complex proteins in the anterior cingulate cortex of adolescent male offspring suggested that this sex-specific effect was enduring. Functionally, offspring exposed to oxytocin-induced uterine hypercontractility showed male-specific abnormalities in social behavior with associated region-specific changes in gene expression and functional cortical connectivity. Our findings, therefore, indicate that even transient but severe placental ischemia-hypoxemia could be detrimental to the developing brain and point to a possible mitochondrial link between intrauterine asphyxia and neurodevelopmental disorders

    Constraints on Earth system functioning at the Paleocene-Eocene Thermal Maximum from the marine silicon cycle

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    The Paleocene‐Eocene Thermal Maximum (PETM, ca. 56 Ma) is marked by a negative carbon isotope excursion (CIE) and increased global temperatures. The CIE is thought to result from the release of 13C‐depleted carbon, although the source(s) of carbon and triggers for its release, its rate of release, and the mechanisms by which the Earth system recovered are all debated. Many of the proposed mechanisms for the onset and recovery phases of the PETM make testable predictions about the marine silica cycle, making silicon isotope records a promising tool to address open questions about the PETM. We analyzed silicon isotope ratios (ή30Si) in radiolarian tests and sponge spicules from the Western North Atlantic (ODP Site 1051) across the PETM. Radiolarian ή30Si decreases by 0.6‰ from a background of 1‰ coeval with the CIE, while sponge ή30Si remains consistent at 0.2‰. Using a box model to test the Si cycle response to various scenarios, we find the data are best explained by a weak silicate weathering feedback, implying the recovery was mostly driven by nondiatom organic carbon burial, the other major long‐term carbon sink. We find no resolvable evidence for a volcanic trigger for carbon release, or for a change in regional oceanography. Better understanding of radiolarian Si isotope fractionation and more Si isotope records spanning the PETM are needed to confirm the global validity of these conclusions, but they highlight how the coupling between the silica and carbon cycles can be exploited to yield insight into the functioning of the Earth system

    The Toll-Like Receptor Signaling Molecule Myd88 Contributes to Pancreatic Beta-Cell Homeostasis in Response to Injury

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    Commensal flora and pathogenic microbes influence the incidence of diabetes in animal models yet little is known about the mechanistic basis of these interactions. We hypothesized that Myd88, an adaptor molecule in the Toll-like-receptor (TLR) pathway, regulates pancreatic ÎČ-cell function and homeostasis. We first examined ÎČ-cells histologically and found that Myd88−/− mice have smaller islets in comparison to C57Bl/6 controls. Myd88−/− mice were nonetheless normoglycemic both at rest and after an intra-peritoneal glucose tolerance test (IPGTT). In contrast, after low-dose streptozotocin (STZ) challenge, Myd88−/−mice had an abnormal IPGTT relative to WT controls. Furthermore, Myd88−/− mice suffer enhanced ÎČ-cell apoptosis and have enhanced hepatic damage with delayed recovery upon low-dose STZ treatment. Finally, we treated WT mice with broad-spectrum oral antibiotics to deplete their commensal flora. In WT mice, low dose oral lipopolysaccharide, but not lipotichoic acid or antibiotics alone, strongly promoted enhanced glycemic control. These data suggest that Myd88 signaling and certain TLR ligands mediate a homeostatic effect on ÎČ-cells primarily in the setting of injury

    Late Cenozoic tephrostratigraphy offshore the southern Central American Volcanic Arc: 1. Tephra ages and provenance

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    We studied the tephra inventory of 18 deep sea drill sites from six DSDP/ODP legs (Legs 84, 138, 170, 202, 205, 206) and two IODP legs (Legs 334 and 344) offshore the southern Central American Volcanic Arc (CAVA). Eight drill sites are located on the incoming Cocos plate and ten drill sites on the continental slope of the Caribbean plate. In total we examined ∌840 ash-bearing horizons and identified ∌650 of these as primary ash beds of which 430 originated from the CAVA. Correlations of ash beds were established between marine cores and with terrestrial tephra deposits, using major and trace element glass compositions with respect to relative stratigraphic order. As a prerequisite for marine-terrestrial correlations we present a new geochemical data set for significant Neogene and Quaternary Costa Rican tephras. Moreover, new Ar/Ar ages for marine tephras have been determined and marine ash beds are also dated using the pelagic sedimentation rates. The resulting correlations and provenance analyses build a tephrochronostratigraphic framework for Costa Rica and Nicaragua that covers the last >8 Myr. We define 39 correlations of marine ash beds to specific tephra formations in Costa Rica and Nicaragua; from the 4.15 Ma Lower Sandillal Ignimbrite to the 3.5 ka RincĂłn de la Vieja Tephra from Costa Rica, as well as another 32 widely distributed tephra layers for which their specific region of origin along Costa Rica and Nicaragua can be constrained

    Impairment of circulating endothelial progenitors in Down syndrome

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    <p>Abstract</p> <p>Background</p> <p>Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome.</p> <p>Methods</p> <p>Circulating endothelial progenitors of Down syndrome affected individuals were isolated, <it>in vitro </it>cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of <it>CXCL12 </it>gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis.</p> <p>Results</p> <p>We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells.</p> <p>Conclusions</p> <p>Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.</p

    THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors

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    The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate
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