Estimation of Laceration Length by Emergency Department Personnel

Introduction Documentation and billing for laceration repair involves a description of wound length. We designed this study to test the hypothesis that emergency department (ED) personnel can accurately estimate wound lengths without the aid of a measuring device. Methods This was a single-center prospective observational study performed in an academic ED. Seven wounds of varying lengths were simulated by creating lacerations on purchased pigs’ ears and feet. We asked healthcare providers, defined as nurses and physicians working in the ED, to estimate the length of each wound by visual inspection. Length estimates were given in centimeters (cm) and inches. Estimated lengths were considered correct if the estimate was within 0.5 cm or 0.2 inches of the actual length. We calculated the differences between estimated and actual laceration lengths for each laceration and compared the accuracy of physicians to nurses using an unpaired t-test. Results Thirty-two physicians (nine faculty and 23 residents) and 16 nurses participated. All subjects tended to overestimate in cm and inches. Physicians were able to estimate laceration length within 0.5 cm 36% of the time and within 0.2 inches 29% of the time. Physicians were more accurate at estimating wound lengths than nurses in both cm and inches. Both physicians and nurses were more accurate at estimating shorter lengths (5.0 cm). Conclusion ED personnel are often unable to accurately estimate wound length in either cm or inches and tend to overestimate laceration lengths when based solely on visual inspection

The Economic Impact of Blindness in Europe

Purpose: To estimate the annual loss of productivity from blindness and moderate to severe visual impairment (MSVI) in the population aged >50 years in the European Union (EU). Methods: We estimated the cost of lost productivity using three simple models reported in the literature based on (1) minimum wage (MW), (2) gross national income (GNI), and (3) purchasing power parity-adjusted gross domestic product (GDP-PPP) losses. In the first two models, assumptions included that all individuals worked until 65 years of age, and that half of all visual impairment cases in the >50-year age group would be in those aged between 50 and 65 years. Loss of productivity was estimated to be 100% for blind individuals and 30% for those with MSVI. None of these models included direct medical costs related to visual impairment. Results: The estimated number of blind people in the EU population aged >50 years is ~1.28 million, with a further 9.99 million living with MSVI. Based on the three models, the estimated cost of blindness is €7.81 billion, €6.29 billion and €17.29 billion and that of MSVI €18.02 billion, €24.80 billion and €39.23 billion, with their combined costs €25.83 billion, €31.09 billion and €56.52 billion, respectively. The estimates from the MW and adjusted GDP-PPP models were generally comparable, whereas the GNI model estimates were higher, probably reflecting the lack of adjustment for unemployment. Conclusion: The cost of blindness and MSVI in the EU is substantial. Wider use of available cost-effective treatment and prevention strategies may reduce the burden significantly

A YoeB toxin cleaves both RNA and DNA

Type II toxin-antitoxin systems contain a toxin protein, which mediates diverse interactions within the bacterial cell when it is not bound by its cognate antitoxin protein. These toxins provide a rich source of evolutionarily-conserved tertiary folds that mediate diverse catalytic reactions. These properties make toxins of interest in biotechnology applications, and studies of the catalytic mechanisms continue to provide surprises. In the current work, our studies on a YoeB family toxin from Agrobacterium tumefaciens have revealed a conserved ribosome-independent non-specific nuclease activity. We have quantified the RNA and DNA cleavage activity, revealing they have essentially equivalent dose-dependence while differing in requirements for divalent cations and pH sensitivity. The DNA cleavage activity is as a nickase for any topology of double-stranded DNA, as well as cleaving single-stranded DNA. AtYoeB is able to bind to double-stranded DNA with mid-micromolar affinity. Comparison of the ribosome-dependent and -independent reactions demonstrates an approximate tenfold efficiency imparted by the ribosome. This demonstrates YoeB toxins can act as non-specific nucleases, cleaving both RNA and DNA, in the absence of being bound within the ribosome.This work was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM103640]. Financial support was provided from the Office of the Vice President for Research and the Office of the Provost, University of Oklahoma. Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye

Crystal structure of Bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative RAB1 provides a structural explanation of potency and selectivity

Bacillus anthracis possesses an innate resistance to the antibiotic trimethoprim due to poor binding to dihydrofolate reductase (DHFR); currently, there are no commercial antibacterials that target this enzyme in B. anthracis. We have previously reported a series of dihydrophthalazine-based trimethoprim derivatives that are inhibitors for this target. In the present work, we have synthesized one compound (RAB1) displaying favorable 50% inhibitory concentration (54 nM) and MIC (</=12.8 ug/ml) values. RAB1 was cocrystallized with the B. anthracis DHFR in the space group P212121, and X-ray diffraction data were collected to a 2.3-A resolution. Binding of RAB1 causes a conformational change of the side chain of Arg58 and Met37 to accommodate the dihydrophthalazine moiety. Unlike the natural substrate or trimethoprim, the dihydrophthalazine group provides a large hydrophobic anchor that embeds within the DHFR active site and accounts for its selective inhibitory activity against B. anthracis.Peer reviewedVeterinary PathobiologyChemistr

Essential role for CD103 in the T cell–mediated regulation of experimental colitis

The integrin CD103 is highly expressed at mucosal sites, but its role in mucosal immune regulation remains poorly understood. We have analyzed the functional role of CD103 in intestinal immune regulation using the T cell transfer model of colitis. Our results show no mandatory role for CD103 expression on T cells for either the development or CD4+CD25+ regulatory T (T reg) cell–mediated control of colitis. However, wild-type CD4+CD25+ T cells were unable to prevent colitis in immune-deficient recipients lacking CD103, demonstrating a nonredundant functional role for CD103 on host cells in T reg cell–mediated intestinal immune regulation. Non–T cell expression of CD103 is restricted primarily to CD11chighMHC class IIhigh dendritic cells (DCs). This DC population is present at a high frequency in the gut-associated lymphoid tissue and appears to mediate a distinct functional role. Thus, CD103+ DCs, but not their CD103− counterparts, promoted expression of the gut-homing receptor CCR9 on T cells. Conversely, CD103− DCs promoted the differentiation of IFN-γ–producing T cells. Collectively, these data suggest that CD103+ and CD103− DCs represent functionally distinct subsets and that CD103 expression on DCs influences the balance between effector and regulatory T cell activity in the intestine

Two possible source regions for Central Greenland last glacial dust

Dust in Greenland ice cores is used to reconstruct the activity of dust-emitting regions and atmospheric circulation. However, the source of dust material to Greenland over the last glacial period is the subject of considerable uncertainty. Here we use new clay mineral and <10 µm Sr–Nd isotopic data from a range of Northern Hemisphere loess deposits in possible source regions alongside existing isotopic data to show that these methods cannot discriminate between two competing hypothetical origins for Greenland dust: an East Asian and/or central European source. In contrast, Hf isotopes (<10 µm fraction) of loess samples show considerable differences between the potential source regions. We attribute this to a first-order clay mineralogy dependence of Hf isotopic signatures in the finest silt/clay fractions, due to absence of zircons. As zircons would also be absent in Greenland dust, this provides a new way to discriminate between hypotheses for Greenland dust sources

Association Rate Constants of Ras-Effector Interactions Are Evolutionarily Conserved

Evolutionary conservation of protein interaction properties has been shown to be a valuable indication for functional importance. Here we use homology interface modeling of 10 Ras-effector complexes by selecting ortholog proteins from 12 organisms representing the major eukaryotic branches, except plants. We find that with increasing divergence time the sequence similarity decreases with respect to the human protein, but the affinities and association rate constants are conserved as predicted by the protein design algorithm, FoldX. In parallel we have done computer simulations on a minimal network based on Ras-effector interactions, and our results indicate that in the absence of negative feedback, changes in kinetics that result in similar binding constants have strong consequences on network behavior. This, together with the previous results, suggests an important biological role, not only for equilibrium binding constants but also for kinetics in signaling processes involving Ras-effector interactions. Our findings are important to take into consideration in system biology approaches and simulations of biological networks

The Herschel–ATLAS data release 2, Paper I. Submillimeter and far-infrared images of the South and North Galactic Poles: the largest Herschel survey of the extragalactic sky

We present the largest submillimeter images that have been made of the extragalactic sky. The Herschel Astrophysical Terahertz Large Area Survey (H-ATLAS) is a survey of 660 deg2 with the PACS and SPIRE cameras in five photometric bands: 100, 160, 250, 350, and 500 μm. In this paper we present the images from our two largest fields, which account for ~75% of the survey. The first field is 180.1 deg2 in size, centered on the north Galactic pole (NGP), and the second is 317.6 deg2 in size, centered on the south Galactic pole. The NGP field serendipitously contains the Coma cluster. Over most (~80%) of the images, the pixel noise, including both instrumental noise and confusion noise, is approximately 3.6, and 3.5 mJy pix−1 at 100 and 160 μm, and 11.0, 11.1 and 12.3 mJy beam−1 at 250, 350 and 500 μm, respectively, but reaches lower values in some parts of the images. If a matched filter is applied to optimize point-source detection, our total 1σ map sensitivity is 5.7, 6.0, and 7.3 mJy at 250, 350, and 500 μm, respectively. We describe the results of an investigation of the noise properties of the images. We make the most precise estimate of confusion in SPIRE maps to date, finding values of 3.12 ± 0.07, 4.13 ± 0.02, and 4.45 ± 0.04 mJy beam−1 at 250, 350, and 500 μm in our un-convolved maps. For PACS we find an estimate of the confusion noise in our fast-parallel observations of 4.23 and 4.62 mJy beam−1 at 100 and 160 μm. Finally, we give recipes for using these images to carry out photometry, both for unresolved and extended sources

AChBP-targeted α-conotoxin correlates distinct binding orientations with nAChR subtype selectivity

Neuronal nAChRs are a diverse family of pentameric ion channels with wide distribution throughout cells of the nervous and immune systems. However, the role of specific subtypes in normal and pathological states remains poorly understood due to the lack of selective probes. Here, we used a binding assay based on acetylcholine-binding protein (AChBP), a homolog of the nicotinic acetylcholine ligand-binding domain, to discover a novel α-conotoxin (α-TxIA) in the venom of Conus textile. α-TxIA bound with high affinity to AChBPs from different species and selectively targeted the α3β2 nAChR subtype. A co-crystal structure of Ac-AChBP with the enhanced potency analog TxIA(A10L), revealed a 20° backbone tilt compared to other AChBP–conotoxin complexes. This reorientation was coordinated by a key salt bridge formed between Arg5 (TxIA) and Asp195 (Ac-AChBP). Mutagenesis studies, biochemical assays and electrophysiological recordings directly correlated the interactions observed in the co-crystal structure to binding affinity at AChBP and different nAChR subtypes. Together, these results establish a new pharmacophore for the design of novel subtype-selective ligands with therapeutic potential in nAChR-related diseases

Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1

Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome-wide significant levels in studying complex disorders; however, when sample size is limited, the true effects may fail to achieve genome-wide significance. In such case, there may be authentic results among the pools of nominal candidates, and an alternative approach is to consider nominal candidates but are replicable across different samples. Here, we found that mRNA expression of the choline dehydrogenase gene (CHDH) was uniformly upregulated in the brains of bipolar disorder (BPD) patients compared with healthy controls across different studies. Follow-up genetic analyses of CHDH variants in multiple independent clinical datasets (including 11,564 cases and 17,686 controls) identified a risk SNP rs9836592 showing consistent associations with BPD (P meta = 5.72 × 10(-4)), and the risk allele indicated an increased CHDH expression in multiple neuronal tissues (lowest P = 6.70 × 10(-16)). These converging results may identify a nominal but true BPD susceptibility gene CHDH. Further exploratory analysis revealed suggestive associations of rs9836592 with childhood intelligence (P = 0.044) and educational attainment (P = 0.0039), a 'proxy phenotype' of general cognitive abilities. Intriguingly, the CHDH gene is located at chromosome 3p21.1, a risk region implicated in previous BPD genome-wide association studies (GWAS), but CHDH is lying outside of the core GWAS linkage disequilibrium (LD) region, and our studied SNP rs9836592 is ∼1.2 Mb 3' downstream of the previous GWAS loci (e.g., rs2251219) with no LD between them; thus, the association observed here is unlikely a reflection of previous GWAS signals. In summary, our results imply that CHDH may play a previously unknown role in the etiology of BPD and also highlight the informative value of integrating gene expression and genetic code in advancing our understanding of its biological basis