bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxymetazoline and hypertensive crisis in a child: can we prevent it?
Authors: Latham Gregory J. , Jardine David S. 
Published: May 2013

SummaryBackgroundOxymetazoline nasal spray is not FDA approved for use in children less than 6 years; however, its safety and efficacy are widely accepted, and it is in widespread use in children prior to procedures that may lead to epistaxis. We report a case of intraoperative oxymetazoline toxicity in a 4‐year‐old boy that led to a hypertensive crisis. While examining the possible causes for this problem, we became aware that the method of drug delivery led to an unanticipated overdose. The position in which the bottle is held causes pronounced variation in the quantity of oxymetazoline dispensed.MethodsTo examine the impact that bottle position has on the volume delivered, we measured the volume of oxymetazoline dispensed with the bottle in the upright and inverted position. We also measured the volume of a drop of oxymetazoline dispensed from the bottle. Because an additional source of oxymetazoline exposure is from packing the nares with surgical pledgets, we analyzed the volume of oxymetazoline absorbed by each pledget.ResultsSqueezing the bottle in the upright position results in a fine spray of fluid that averaged 28.9 ± 6.8 μl and was largely independent of effort. This volume is nearly identical to the measured volume of a drop of oxymetazoline, which was 30 μl. However, squeezing the bottle in the inverted position resulted in a steady stream of fluid, and the volume administered was completely effort dependent. Multiple tests in the inverted position demonstrated an average volume of 1037 ± 527 μl, with a range of 473–2196 μl. Lastly, the volume of oxymetazoline absorbed by each surgical pledget was 1511 ± 184 μl.DiscussionOur testing indicates that bottle position during oxymetazoline administration can cause up to a 75‐fold increase in intended drug administration.
The mouse ruby‐eye 2d (ru2d/Hps5ru2‐d) allele inhibits eumelanin but not pheomelanin synthesis
Authors: Hirobe Tomohisa , Ito Shosuke , Wakamatsu Kazumasa 
Published: May 2013

SummaryThe novel mutation named ru2d/Hps5ru2‐d, characterized by light‐colored coats and ruby‐eyes, prohibits differentiation of melanocytes by inhibiting tyrosinase (Tyr) activity, expression of Tyr, Tyr‐related protein 1 (Tyrp1), Tyrp2, and Kit. However, it is not known whether the ru2d allele affects pheomelanin synthesis in recessive yellow (e/Mc1re) or in pheomelanic stage in agouti (A) mice. In this study, effects of the ru2d allele on pheomelanin synthesis were investigated by chemical analysis of melanin present in dorsal hairs of 5‐week‐old mice from F2 generation between C57BL/10JHir (B10)‐co‐isogenic ruby‐eye 2d and B10‐congenic recessive yellow or agouti. Eumelanin content was decreased in ruby‐eye 2d and ruby‐eye 2d agouti mice, whereas pheomelanin content in ruby‐eye 2d recessive yellow and ruby‐eye 2d agouti mice did not differ from the corresponding Ru2d/‐ mice, suggesting that the ru2d allele inhibits eumelanin but not pheomelanin synthesis.
A Prospective Two‐Year Assessment of Miconazole Resistance in Candida Spp. with Repeated Treatment with 0.25% Miconazole Nitrate Ointment in Neonates and Infants with Moderate to Severe Diaper Dermatitis Complicated by Cutaneous Candidiasis
Authors: Blanco Daisy , van Rossem Koen 
Published: May 2013

AbstractA petrolatum and zinc oxide–based ointment containing 0.25% miconazole nitrate is reported to be effective and well tolerated in the treatment of diaper dermatitis complicated by cutaneous candidiasis (DDCC). This prospective, multicenter, open‐label, long‐term, phase IV study investigated the potential resistance of Candida spp. to repeated topical use of 0.25% miconazole nitrate in infants age 15 months and younger with moderate to severe DDCC. For initial and recurring episodes of DDCC over the 2‐year study period, subjects were treated with a 7‐day course of 0.25% miconazole nitrate ointment (active components: miconazole nitrate 0.25%, zinc oxide 15%, and white petrolatum 81.35%) with a 7‐day follow‐up. Clinical and mycologic evaluations were conducted before treatment (day 0) and 7 days after treatment (day 14). Potential resistance to miconazole was defined using an arbitrary breakpoint of minimum inhibitory concentration of 2 μg/mL. There was no evidence of resistance to miconazole in Candida spp. after single or repeated treatment courses of 0.25% miconazole nitrate ointment. For the initial episode of DDCC, 83 of 168 subjects (49.4%) achieved a clinical cure, 77 (45.8%) achieved a mycologic cure, and 49 (29.2%) achieved an overall cure (clinical and mycologic). The overall cure rate for recurrent episodes of DDCC was similar to or numerically greater than rates observed for the initial episode. Treatment of DDCC with 0.25% miconazole nitrate ointment was effective and generally well tolerated. No evidence of the development of resistance to miconazole in Candida spp. was observed.
Resistance against Botrytis cinerea in smooth leaf pruning wounds of tomato does not depend on major disease signalling pathways
Authors: Beyers T. , Vos C. , Aerts R. , Heyens K. , Vogels L. , Seels B. , Höfte M. , Cammue B. P. A. , De Coninck B. 
Published: May 2013

In high‐tech, heated tomato glasshouses, stem infections caused by Botrytis cinerea usually end up girdling the stem, resulting in plant death and consequently high economic losses. Such infections originate primarily from wounds created during leaf pruning, a common cultural practice in which it is intended to remove leaves completely, resulting in smooth stem wounds. However, hasty leaf pruning often results in numerous petiole stubs accidentally left behind. In this study analysis of disease incidences clearly proved that pruning leaves flush to the stem resulted in absolute resistance of the stem wounds, whereas petiole stubs displayed a high level of susceptibility to B. cinerea. Postponing inoculation of wounds after pruning indicated that development of nearly complete resistance occurs within 48 h after deleafing. Monitoring of the wound wetness period showed that drying of the wound surface is not the cause of the decreased susceptibility, contrary to what was commonly believed. Tomato mutants deficient in disease signalling showed altered phenotypes for susceptibility to B. cinerea, indicating that defences against this pathogen in petiole stubs depend on ethylene signalling. Additionally, the decreased susceptibility of mutants deficient in the biosynthesis of jasmonates and abscisic acid suggest an antagonistic effect of these signal molecules. On the other hand, resistance of smooth stem wounds could not be altered by disruption of salicylic acid, ethylene, jasmonate or abscisic acid signalling. This indicates that this remarkable absolute resistance to B. cinerea does not depend on the major disease signalling pathways.
Phylogenetic revision of the North American Asidini (Coleoptera: Tenebrionidae)
Authors: SMITH AARON D. 
Published: May 2013

AbstractThe asidine darkling beetles (Coleoptera: Tenebrionidae: Asidini) are a morphologically diverse tribe of flightless tenebrionids found in many arid and sub‐arid habitats around the world. The 260 currently described North American species are contained in 27 genera, all of which are restricted to the western half of the continent. Evolutionary relationships within and between the North American Asidini (Coleoptera: Tenebrionidae) genera were reconstructed using partial sequences of mitochondrial cytochrome c oxidase I (COI) (660 bp) and nuclear ribosomal 28S (D2 region) (492 bp), and 100 phenotypic characters for 50 North American asidine species, representing 20 of the 27 currently described genera and 1 new genus. Species from two additional tenebrionid tribes (Branchini and Coniontini) and the South American asidine genus Cardigenius were chosen as outgroups. Analyses were performed using maximum parsimony and Bayesian inference methods. Clade support was inferred based on the posterior probability distribution of tree topologies, nonparametric bootstrap analysis, and partitioned Bremer support indices. The generic classification of the North American Asidini is revised based on the results, with ten genera recognized. Seven current genera: Craniotus LeConte, Heterasida Casey, Litasida Casey, Microschatia Solier, Pelecyphorus Solier, Philolithus Lacordaire, Stenomorpha Solier, are redescribed, and Ardamimicus Smith gen.n., Ferveoventer Smith gen.n. and Micrasida Smith gen.n. are described, including Ardamimicus cognatoi Smith sp.n., Ferveoventer browni Smith sp.n. and Micrasida obrienorum Smith sp.n. Twenty current genera are treated as subgenera pending further analyses: Philolithus Lacordaire with subgenera Glyptasida Casey, Gonasida Casey, Herthasida Wilke and Tisamenes Champion; Pelecyphorus Solier, with subgenera: Astrotus LeConte, Parasida Casey (= Plesiasida nom.n), Poliorcetes Champion, Sicharbas Champion, Stenosides Solier, Ucalegon Champion and Zaleucus Champion, and Stenomorpha Solier with subgenera Asidina Casey, Asidopsis Casey, Bothrasida Casey, Megasida Casey, Notiasida Casey, Platasida Casey, Pycnomorpha Motschulsky, Stethasida Casey and Trichiasida Casey; all stat.rev.
Hospital‐based transfusion error tracking from 2005 to 2010: identifying the key errors threatening patient transfusion safety
Authors: Maskens Carolyn , Downie Helen , Wendt Alison , Lima Ana , Merkley Lisa , Lin Yulia , Callum Jeannie 
Published: May 2013

BackgroundThis report provides a comprehensive analysis of transfusion errors occurring at a large teaching hospital and aims to determine key errors that are threatening transfusion safety, despite implementation of safety measures.Study Design and MethodsErrors were prospectively identified from 2005 to 2010. Error data were coded on a secure online database called the Transfusion Error Surveillance System. Errors were defined as any deviation from established standard operating procedures. Errors were identified by clinical and laboratory staff. Denominator data for volume of activity were used to calculate rates.ResultsA total of 15,134 errors were reported with a median number of 215 errors per month (range, 85‐334). Overall, 9083 (60%) errors occurred on the transfusion service and 6051 (40%) on the clinical services. In total, 23 errors resulted in patient harm: 21 of these errors occurred on the clinical services and two in the transfusion service. Of the 23 harm events, 21 involved inappropriate use of blood. Errors with no harm were 657 times more common than events that caused harm. The most common high‐severity clinical errors were sample labeling (37.5%) and inappropriate ordering of blood (28.8%). The most common high‐severity error in the transfusion service was sample accepted despite not meeting acceptance criteria (18.3%). The cost of product and component loss due to errors was $593,337.ConclusionErrors occurred at every point in the transfusion process, with the greatest potential risk of patient harm resulting from inappropriate ordering of blood products and errors in sample labeling.
Lung sparing and dose escalation in a robust‐inspired IMRT planning method for lung radiotherapy that accounts for intrafraction motion
Authors: McCann Claire , Purdie Thomas , Hope Andrew , Bezjak Andrea , Bissonnette Jean‐Pierre 
Published: May 2013

Purpose:To test the efficacy of a simple, robust‐inspired intensity modulated radiotherapy (IMRT) planning strategy for lung radiotherapy designed to reduce lung dose and escalate tumor dose using realistic dose accumulation tools.Methods:A deformable image registration tool was used to plan and accumulate dose over all phases of the breathing cycle for conventional and robust‐inspired IMRT strategies of eight nonsmall cell lung cancer patients exhibiting peak‐to‐peak respiratory motion with amplitudes ranging from 1 to 2 cm in the craniocaudal direction. The authors’ robust‐inspired plans were designed to have smaller beam apertures based on target location during exhale, combined with edge‐enhanced intensity maps to ensure target coverage during inspiration. For these, a new planning target volume defined as the rPTV was generated from a 5‐mm isotropic expansion of the clinical target volume (CTV) on end‐exhale combined with a boost volume, set to 110% of the prescription dose. Plans were evaluated in terms of (i) lung sparing and (ii) dose escalation for mean lung dose (MLD) isotoxicity. CTV and planning target volumes (PTV) coverage and lung dose were compared to the conventional IMRT approach.Results:Robust‐inspired plans showed potential lung dose reductions in seven out of eight patients. For non‐GTV lung, percent reductions of 3%–14% in MLD and 6%–15% in V20 were observed. For seven of eight cases, the robust‐like approach yielded increased accumulated doses to CTV. Isotoxicity studies for MLD showed increased dose to the CTV and the rPTV, in the range of 104%–118% and 95%–114% of prescription dose, respectively.Conclusions:A 4D dose calculation based on deformable image registration was used to evaluate a robust‐inspired planning strategy for lung radiotherapy. This method offers notable reductions to lung dose while improving tumor coverage through the use of reduced geometric margins combined with edge enhancements.
Induction of Dendritic Cell Production of Type I and Type III Interferons by Wild-Type and Vaccine Strains of Measles Virus: Role of Defective Interfering RNAs
Authors: Shivakoti Rupak , Siwek Martina , Hauer Debra , Schultz Kimberly L. W. , Griffin Diane E. 
Published: May 2013

ABSTRACT

The innate immune response to viral infection frequently includes induction of type I interferons (IFN), but many viruses have evolved ways to block this response and increase virulence.
In vitro
studies of IFN production after infection of susceptible cells with measles virus (MeV) have often reported greater IFN synthesis after infection with vaccine than with wild-type strains of MeV. However, the possible presence in laboratory virus stocks of 5′ copy-back defective interfering (DI) RNAs that induce IFN independent of the standard virus has frequently confounded interpretation of data from these studies. To further investigate MeV strain-dependent differences in IFN induction and the role of DI RNAs, monocyte-derived dendritic cells (moDCs) were infected with the wild-type Bilthoven strain and the vaccine Edmonston-Zagreb strain with and without DI RNAs. Production of type I IFN, type III IFN, and the interferon-stimulated genes (ISGs) Mx and ISG56 by infected cells was assessed with a flow cytometry-based IFN bioassay, quantitative reverse transcriptase PCR (RT-PCR), and immunoassays. Bilthoven infected moDCs less efficiently than Edmonston-Zagreb. Presence of DI RNAs in vaccine stocks resulted in greater maturation of moDCs, inhibition of virus replication, and induction of higher levels of IFN and ISGs. Production of type I IFN, type III IFN, and ISG mRNA and protein was determined by both the level of infection and the presence of DI RNAs. At the same levels of infection and in the absence of DI RNA, IFN induction was similar between wild-type and vaccine strains of MeV.
Adaptor Protein 1 Promotes Cross-Presentation through the Same Tyrosine Signal in Major Histocompatibility Complex Class I as That Targeted by HIV-1
Authors: Kulpa Deanna A. , Del Cid Natasha , Peterson Kirsten A. , Collins Kathleen L. 
Published: May 2013

ABSTRACT

Certain antigen-presenting cells (APCs) process and present extracellular antigen with major histocompatibility complex class I (MHC-I) molecules to activate naive CD8
+
T cells in a process termed cross-presentation. We used insights gained from HIV immune evasion strategies to demonstrate that the clathrin adaptor protein adaptor protein 1 (AP-1) is necessary for cross-presentation by MHC-I molecules containing a cytoplasmic tail tyrosine signal (murine MHC-I molecules, human MHC-I HLA-A and HLA-B allotypes). In contrast, AP-1 activity was not needed for cross-presentation by MHC-I molecules containing a human MHC-I HLA-C cytoplasmic tail, which does not contain a tyrosine signal. AP-1 activity was also dispensable for presentation of endogenous antigens by MHC-I via the classical pathway. In APCs, we show that HIV Nef disrupts cross-presentation by MHC-I containing the tyrosine signal but does not affect cross-presentation by MHC-I containing the HLA-C cytoplasmic tail. Thus, we provide evidence for two separable cross-presentation pathways, only one of which is targeted by HIV.
Analysis of the Role of Vaccinia Virus H7 in Virion Membrane Biogenesis with an H7-Deletion Mutant
Authors: Meng Xiangzhi , Wu Xiang , Yan Bo , Deng Junpeng , Xiang Yan 
Published: May 2013

ABSTRACT
Essential vaccinia virus genes are often studied with conditional-lethal inducible mutants. Here, we constructed a deletion mutant lacking the essential H7R gene (the ΔH7 mutant) with an H7-expressing cell line. Compared to an inducible H7 mutant, the ΔH7 mutant showed a defect at an earlier step of virion membrane biogenesis, before the development of short crescent-shaped precursors of the viral envelope. Our studies refine the role of H7 in virion membrane biogenesis and highlight the values of analyzing deletion mutants.
Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus Entry That Act by Three Distinct Mechanisms
Authors: Adedeji Adeyemi O. , Severson William , Jonsson Colleen , Singh Kamalendra , Weiss Susan R. , Sarafianos Stefan G. 
Published: May 2013

ABSTRACT

Severe acute respiratory syndrome (SARS) is an infectious and highly contagious disease that is caused by SARS coronavirus (SARS-CoV) and for which there are currently no approved treatments. We report the discovery and characterization of small-molecule inhibitors of SARS-CoV replication that block viral entry by three different mechanisms. The compounds were discovered by screening a chemical library of compounds for blocking of entry of HIV-1 pseudotyped with SARS-CoV surface glycoprotein S (SARS-S) but not that of HIV-1 pseudotyped with vesicular stomatitis virus surface glycoprotein G (VSV-G). Studies on their mechanisms of action revealed that the compounds act by three distinct mechanisms: (i) SSAA09E2 {
N
-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,2-oxazole-5-carboxamide} acts through a novel mechanism of action, by blocking early interactions of SARS-S with the receptor for SARS-CoV, angiotensin converting enzyme 2 (ACE2); (ii) SSAA09E1 {[(
Z
)-1-thiophen-2-ylethylideneamino]thiourea} acts later, by blocking cathepsin L, a host protease required for processing of SARS-S during viral entry; and (iii) SSAA09E3 [
N
-(9,10-dioxo-9,10-dihydroanthracen-2-yl)benzamide] also acts later and does not affect interactions of SARS-S with ACE2 or the enzymatic functions of cathepsin L but prevents fusion of the viral membrane with the host cellular membrane. Our work demonstrates that there are at least three independent strategies for blocking SARS-CoV entry, validates these mechanisms of inhibition, and introduces promising leads for the development of SARS therapeutics.
Epstein-Barr Virus-Encoded MicroRNA BART15-3p Promotes Cell Apoptosis Partially by Targeting BRUCE
Authors: Choi Hoyun , Lee Hanna , Kim Sae Rom , Gho Yong Song , Lee Suk Kyeong 
Published: May 2013

ABSTRACT
Epstein-Barr Virus (EBV) generates a variety of viral microRNAs (miRNAs) by processing the BHRF1 and BamHI A rightward (BART) transcripts. BART miRNAs are expressed in all cells latently infected with EBV, but the functions of most BART miRNAs remain unknown. The results of a cell proliferation assay revealed that miR-BART15-3p inhibited cell proliferation. Fluorescence-activated cell sorting following staining with annexin V or propidium iodide showed that miR-BART15-3p promoted apoptosis. Furthermore, the inhibitor for miR-BART15-3p increased cell growth and reduced apoptosis in EBV-infected cells. Using bioinformatic analyses, we predicted that miR-BART15-3p may target the antiapoptotic B-cell lymphoma 2 (BCL2), BCL2L2, DEAD (Asp-Glu-Ala-Asp) box polypeptide 42 (DDX42), and baculovirus inhibitor of apoptosis repeat-containing ubiquitin-conjugating enzyme (BRUCE) mRNAs. The luciferase reporter assay showed that only the 3′ untranslated region (UTR) of BRUCE was affected by miR-BART15-3p. Two putative seed-matched sites for miR-BART15-3p were evident on the BRUCE 3′ UTR. The results of a mutation study indicated that miR-BART15-3p hybridized only with the first seed-matched site on the BRUCE 3′ UTR. miR-BART15-3p downregulated the BRUCE protein in EBV-negative cells, while the inhibitor for miR-BART15-3p upregulated the BRUCE protein in EBV-infected cells without affecting the BRUCE mRNA level. miR-BART15-3p was secreted from EBV-infected gastric carcinoma cells, and the level of miR-BART15-3p was 2- to 16-fold higher in exosomes than in the corresponding cells. Our data suggest that miR-BART15-3p can induce apoptosis partially by inhibiting the translation of the apoptosis inhibitor BRUCE. Further study is warranted to understand the role of miR-BART15-3p in the EBV life cycle.
Phosphorylation of Kaposi's Sarcoma-Associated Herpesvirus Processivity Factor ORF59 by a Viral Kinase Modulates Its Ability To Associate with RTA and
ori
Lyt
Authors: McDowell Maria E. , Purushothaman Pravinkumar , Rossetto Cyprian C. , Pari Gregory S. , Verma Subhash C. 
Published: May 2013

ABSTRACT

ORF59 of Kaposi's sarcoma-associated herpesvirus (KSHV) plays an essential role in viral lytic replication by providing DNA processivity activity to the viral DNA polymerase (ORF9). ORF59 forms a homodimer in the cytoplasm and binds and translocates ORF9 into the nucleus, where it secures ORF9 to the origin of lytic DNA replication (
ori
Lyt) in order to synthesize long DNA fragments during replication. ORF59 binds to
ori
Lyt through an immediate early protein, replication and transcription activator (RTA). Here, we show that viral kinase (ORF36) phosphorylates serines between amino acids 376 and 379 of ORF59 and replacement of the Ser378 residue with alanine significantly impairs phosphorylation. Although mutating these serine residues had no effect on binding between ORF59 and ORF9, viral polymerase, or ORF36, the viral kinase, it significantly reduced the ability of ORF59 to bind to RTA. The results for the mutant in which Ser376 to Ser379 were replaced by alanine showed that both Ser378 and Ser379 contribute to binding to RTA. Additionally, the Ser376, Ser378, and Ser379 residues were found to be critical for binding of ORF59 to
ori
Lyt and its processivity function. Ablation of these phosphorylation sites reduced the production of virion particles, suggesting that phosphorylation is critical for ORF59 activity and viral DNA synthesis.