Impact of a New Medical Record System for Emergency Departments Designed to Accelerate Clinical Documentation: A Crossover Study.

Recording information in emergency departments (EDs) constitutes a major obstacle to efficient treatment. A new electronic medical records (EMR) system focusing on clinical documentation was developed to accelerate patient flow. The aim of this study was to examine the impact of a new EMR system on ED length of stay and physician satisfaction.We integrated a new EMR system at a hospital already using a standard system. A crossover design was adopted whereby residents were randomized into 2 groups. Group A used the existing EMR system first, followed by the newly developed system, for 2 weeks each. Group B followed the opposite sequence. The time required to provide overall medical care, length of stay in ED, and degree of physician satisfaction were compared between the 2 EMR systems.The study involved 6 residents and 526 patients (277 assessed using the standard system and 249 assessed with the new system). Mean time for clinical documentation decreased from 133.7 ± 5.1 minutes to 107.5 ± 5.4 minutes with the new EMR system (P < 0.001). The time for overall medical care was significantly reduced in all patient groups except triage level 5 (nonurgent). The new EMR system significantly reduced the length of stay in ED for triage level 2 (emergency) patients (145.4 ± 13.6 minutes vs 184.3 ± 13.6 minutes for standard system; P = 0.047). As for the degree of physician satisfaction, there was a high degree of satisfaction in terms of the physical findings support system and the ability to capture images and enter negative findings.The new EMR system shortened the time for overall medical care and was associated with a high degree of resident satisfaction

LPS modulates the expression of iron-related immune genes in two Antarctic notothenoids

The non-specific immunity can induce iron deprivation as a defense mechanism against potential bacterial pathogens, but little information is available as to its role in Antarctic fish. In this study the response of iron metabolism related genes was evaluated in liver and head kidney of the Antarctic notothenoids Notothenia coriiceps and Notothenia rossii 7 days after lipopolysaccharide (LPS) injection. Average plasma Fe2+ concentration was unaffected by treatment in any of the species. The gene expression response to LPS varied between tissues and species, being stronger in N. coriiceps and more prominent in the head kidney than liver. The reaction to LPS was marked by increased individual variability in most genes analyzed, even when the change in expression was not statistically significant, suggesting different individual sensitivity and coping responses in these wild fish. We found that iron related genes had an attenuated and homogenous response to LPS but there was no detectable relationship between plasma Fe2+ and gene expression. However, overall in both tissues and species LPS exposure set a multilevel response that concur to promote intracellular accumulation of iron, an indication that Antarctic Notothenoids use innate nutritional immunity as a resistance mechanism against pathogens.FCT-NSFC/0002/2016; CCMAR/Multi/04326/2013; PTDC/BIAANM/3484/2014info:eu-repo/semantics/publishedVersio

Influence of the metabolic state on the tolerance of Pichia kudriavzevii to heavy metals

This work aims to examine the influence of the metabolic state of the yeast Pichia kudriavzevii on the susceptibility to a metals mixture (5mgL1 Cd, 10mgL1 Pb, and 5mgL1 Zn). Cells exposed to the metals mixture in the presence of 25mmolL1 glucose displayed a higher loss of membrane integrity and proliferation capacity, compared to cells incubated in the absence of glucose. The analysis of the effect of individual metals revealed that glucose increased the toxic effect of Cd marginally, and of Pb significantly. The increased susceptibility to heavy metals due to glucose was attenuated in the simultaneous presence of a mitochondrial respiration inhibitor such as sodium azide (NaN3). ATP-depleted yeast cells, resulting from treatment with the non-metabolizable glucose analogue 2-deoxy-d-glucose, showed an increased susceptibility to heavy metals mixture. Pre-incubation of yeast cells with 1 or 1.5mmolL1 Ca2+ reduced significantly (P<0.05) the loss of membrane integrity induced by the metals mixture. These findings contribute to the understanding of metals mechanisms of toxicity in the non-conventional yeast P. kudriavzevii.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER- 027462). Vanessa A. Mesquita and Manuela D. Machado gratefully acknowledge the grant from Coordenaç~ao de Aperfeiçoamento de Pessoal de N ıvel Superior (CAPES) and the post-doctoral grant from FCT (SRH/BPD/72816/ 2010), respectively

Effects of various metal ions on the gene expression of iron exporter ferroportin-1 in J774 macrophages

Macrophages play a key role in iron metabolism by recycling iron through erythrophagocytosis. Ferroportin-1 (FPN1) is a transporter protein that is known to mediate iron export from macrophages. Since divalent metals often interact with iron metabolism, we examined if divalent metals could regulate the expression of FPN1 in macrophages. J774 macrophage cells were treated with copper, manganese, zinc, or cobalt at 10, 50, or 100 µM for 16 to 24 h. Then, FPN1 mRNA and protein levels were determined by quantitative real-time PCR and Western blot analyses, respectively. In addition, effects of divalent metals on FPN1 promoter activity were examined by luciferase reporter assays. Results showed that copper significantly increased FPN1 mRNA levels in a dose-dependent manner. The copper-induced expression of FPN1 mRNA was associated with a corresponding increase in FPN1 protein levels. Also, copper directly stimulated the activity of FPN1 promoter-driven reporter construct. In contrast, manganese and zinc had no effect on the FPN1 gene expression in J774 cells. Interestingly, cobalt treatment in J774 cells decreased FPN1 protein levels without affecting FPN1 mRNA levels. In conclusion, our study results demonstrate that divalent metals differentially regulate FPN1 expression in macrophages and indicate a potential interaction of divalent metals with the FPN1-mediated iron export in macrophages

SIREs: searching for iron-responsive elements

The iron regulatory protein/iron-responsive element regulatory system plays a crucial role in the post-transcriptional regulation of gene expression and its disruption results in human disease. IREs are cis-acting regulatory motifs present in mRNAs that encode proteins involved in iron metabolism. They function as binding sites for two related trans-acting factors, namely the IRP-1 and -2. Among cis-acting RNA regulatory elements, the IRE is one of the best characterized. It is defined by a combination of RNA sequence and structure. However, currently available programs to predict IREs do not show a satisfactory level of sensitivity and fail to detect some of the functional IREs. Here, we report an improved software for the prediction of IREs implemented as a user-friendly web server tool. The SIREs web server uses a simple data input interface and provides structure analysis, predicted RNA folds, folding energy data and an overall quality flag based on properties of well characterized IREs. Results are reported in a tabular format and as a schematic visual representation that highlights important features of the IRE. The SIREs (Search for iron-responsive elements) web server is freely available on the web at http://ccbg.imppc.org/sires/index.htm

Pathophysiology of the Belgrade rat

The Belgrade rat is an animal model of divalent metal transporter 1 (DMT1) deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat’s pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 in iron distribution to red blood cells as well as duodenal iron absorption. The Belgrade rat’s pathology has extended our knowledge of hepatic iron handling, pulmonary and olfactory iron transport as well as brain iron uptake and renal iron handling. For example, relationships between iron and manganese metabolism have been discerned since both are essential metals transported by DMT1. Pathophysiologic features of the Belgrade rat provide us with a unique and interesting animal model to understand iron homeostasis

Cadmium increases ferroportin-1 gene expression in J774 macrophage cells via the production of reactive oxygen species

Cadmium intoxication has been associated with the dysregulation of iron homeostasis. In the present study, we investigated the effect of cadmium on the expression of ferroportin 1 (FPN1), an important iron transporter protein that is involved in iron release from macrophages. When we incubated cadmium with J774 mouse macrophage cells, FPN1 mRNA levels were significantly increased in a dose- and time-dependent manner. Furthermore, the cadmium-induced FPN1 mRNA expression was associated with increased levels of FPN1 protein. On the other hand, cadmium-mediated FPN1 mRNA induction in J774 cells was completely blocked when cells were co-treated with a transcription inhibitor, acitomycin D. Also, cadmium directly stimulated the activity of the FPN1-promoter driven luciferase reporter, suggesting that the cadmium up-regulates FPN1 gene expression in a transcription-dependent manner. Finally, cadmium exposure to J774 macrophages increased intracellular reactive oxygen species (ROS) levels by ~ 2-fold, compared to untreated controls. When J774 cells were co-treated with antioxidant N-acetylcystein, the cadmium-induced FPN1 mRNA induction was significantly attenuated. In summary, the results of this study clearly demonstrated that cadmium increased FPN1 expression in macrophages through a mechanism that involves ROS production, and suggests another important interaction between iron and cadmium metabolism

NMR structures and orientation of the fourth transmembrane domain of the rat divalent metal transporter (DMT1) with G185D mutation in SDS micelles

DMT1, also known as Nramp2, is an iron transporter, and belongs to the family of Nramp proteins. Disease-causing mutations both in Nramp1 and Nramp2 occurring at the conserved two adjacent glycine residues located within the fourth transmembrane domain (TM4) suggest that TM4 may serve an important biological function. In the present study, we have determined the high-resolution structures of a synthetic peptide, corresponding to the sequence of the fourth transmembrane domain of rat DMT1 with G185D mutation, in membrane-mimetic environments (e.g., SDS micelles) using NMR spectroscopy and distance-geometry/simulated annealing calculations. The spatial structures showed a-helices without a kink in the middle portion of the peptide, with a highly flexible and poorly defined N-terminus. Both the N-terminus and the helical core of the peptide were embedded into the SDS micelles. Interestingly, the folding and membrane location of the C-terminus was pH dependent, being well-folded and inserted into SDS micelles only at a low pH value (4.0). The peptide exhibited amphipathic characteristics, with hydrophilic residues (Asp7, Thr11, Asp14, Asp14, and Thr 15) lying in one side of the helix, which provide a basis for the formation of water-filled channel architectures through self-associations. The significant broadening of the resonances of the hydrophilic residues Asp7, Thr11, and Asp14, which are buried inside SDS micelles, upon addition of Mn 2+ further verified the possibility of the formation of a channel through which metal ions pass. The substitution of Gly7 by an aspartate residue neither significantly altered the structure and membrane location of the peptide nor abolished its properties of channel forming and metal permeation compared with the wild-type peptide. © 2005 Wiley Periodicals, Inc.postprin

Iron depletion suppresses mTORC1-directed signalling in intestinal Caco-2 cells via induction of REDD

Acknowledgements This work was supported by grants from the Biotechnology and Biological Science Research Council (BB/I007261/1 and BB/N002342/1) and The Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS 854/11).Peer reviewedPublisher PD

L-DOPA Neurotoxicity Is Mediated by Up-Regulation of DMT1−IRE Expression

2008-2009 > Academic research: refereed > Publication in refereed journalpublished_fina