Search

Abstract Introduction There are no known case reports of hepatic steatosis caused by oral fluoropyrimidines such as capecitabine. With increasing use of capecitabine since its approval for the treatment of metastatic colon cancer in 2001, and more recently for adjuvant treatment of colon cancer and treatment of metastatic breast cancer, we can anticipate increased recognition of potential toxicities associated with this 5-fluorouracil derivative. Case presentation We report the case of a 74-year-old Armenian woman who received capecitabine as adjuvant treatment for colon cancer and subsequently developed abnormal liver biochemical tests and radiographic findings in keeping with hepatic steatosis. There was complete reversal of liver enzyme abnormalities with discontinuation of the drug and this patient represents a case of reversible liver injury due to capecitabine. Conclusion In this original case report, capecitabine use was associated with hepatic steatosis. It is important for clinicians to recognize and monitor for this potential toxicity, which may be a cause of abnormal liver enzymes in this patient population.

The magnetic fields of interplanetary coronal mass ejections (ICMEs), which originate close to the Sun in the form of a flux rope, determine their geoeffectiveness. Therefore, robust flux rope‐based models of CMEs are required to perform magnetohydrodynamic (MHD) simulations aimed at space weather predictions. We propose a modified spheromak model and demonstrate its applicability to CME simulations. In this model, such properties of a simulated CME as the poloidal and toroidal magnetic fluxes, and the helicity sign can be controlled with a set of input parameters. We propose a robust technique for introducing CMEs with an appropriate speed into a background, MHD solution describing the solar wind in the inner heliosphere. Through a parametric study, we find that the speed of a CME is much more dependent on its poloidal flux than on the toroidal flux. We also show that the CME speed increases with its total energy, giving us control over its initial speed. We further demonstrate the applicability of this model to simulations of CME‐CME collisions. Finally, we use this model to simulate the 12 July 2012 CME and compare the plasma properties at 1 AU with observations. The predicted CME properties agree reasonably with observational data. Key Points: CME simulations can be used for predictionThe magnetic and kinematic properties of CMEs must be constrainedModified Spheromak model can robustly simulate CMEs in inner heliosphere [ABSTRACT FROM AUTHOR]

Understanding the molecular basis of how ticks adapt to feed on different animal hosts is central to understanding tick and tick-borne disease (TBD) epidemiology. There is evidence that ticks differentially express specific sets of genes when stimulated to start feeding. This study was initiated to investigate if ticks such as Ixodes scapularis and Amblyomma americanum that are adapted to feed on multiple hosts utilized the same sets of proteins to prepare for feeding. We exposed I. scapularis and A. americanum to feeding stimuli of different hosts (rabbit, human, and dog) by keeping unfed adult ticks enclosed in a perforated microfuge in close contact with host skin, but not allowing ticks to attach on host. Our data suggest that ticks of the same species differentially express tick saliva proteins (TSPs) when stimulated to start feeding on different hosts. SDS-PAGE and silver staining analysis revealed unique electrophoretic profiles in saliva of I. scapularis and A. americanum that were stimulated to feed on different hosts: rabbit, human, and dog. LC-MS/MS sequencing and pairwise analysis demonstrated that I. scapularis and A. americanum ticks expressed unique protein profiles in their saliva when stimulated to start feeding on different hosts: rabbit, dog, or human. Specifically, our data revealed TSPs that were unique to each treatment and those that were shared between treatments. Overall, we identified a total of 276 and 340 non-redundant I. scapularis and A. americanum TSPs, which we have classified into 28 functional classes including: secreted conserved proteins (unknown functions), proteinase inhibitors, lipocalins, extracellularmatrix/cell adhesion, heme/ironmetabolism, signal transduction and immunity-related proteins being the most predominant in saliva of unfed ticks. With exception of research on vaccines against Rhipicephalus microplus, which its natural host, cattle, research on vaccine against other ticks relies feeding ticks on laboratory animals. Data here suggest that relying on lab animal tick feeding data to select target antigens could result in prioritizing irrelevant anti-tick vaccine targets that are expressed when ticks feed on laboratory animals. This study provides the platform that could be utilized to identify relevant target anti-tick vaccine antigens, and will facilitate early stage tick feeding research. [ABSTRACT FROM AUTHOR]

Background: Intraoperative anaphylaxis to neuromuscular blocking agents (NMBAs) is a rare event that is unpredictable and potentially life threatening. Most of the previous reports on such intraoperative anaphylaxis used market share surveys or self-reported data to estimate the incidence.Objective: To determine the incidences of intraoperative anaphylaxis to NMBAs using electronic medical records.Design: A retrospective observational study.Setting: Two tertiary hospitals in South Korea.Patients: This study involved patients exposed to NMBAs during anaesthesia between 1 January 2005 and 31 May 2014. Nineteen episodes were deemed to be intraoperative anaphylaxis to NMBAs.Main Outcome Measures: We calculated the incidences of intraoperative anaphylaxis to NMBAs. Exposure to the agents was determined from intraoperative records maintained in an electronic medical recording system. An anaphylactic reaction was determined from both clinical signs and the results of skin tests.Results: Over 9 years, 729 429 patients were exposed to NMBA, the most frequently used being rocuronium [425 047 (58.3%)] and vecuronium [274 801 (37.7%)]. The overall incidence of intraoperative anaphylaxis was 2.6 per 100 000 (19 cases), and was higher with rocuronium (16 cases, 3.8 per 100 000) than with vecuronium (two cases, 0.7 cases per 100 000), P = 0.014. Comparing the first 3 years with the last 6 years, the incidence of intraoperative rocuronium anaphylaxis appeared to increase 1.4-fold (P = 0.006).Conclusion: Among commonly used NMBAs, rocuronium appears to have the highest incidence of anaphylaxis. Our findings suggest that future prospective investigation for NMBA-induced anaphylaxis should use internationally agreed skin test protocols. [ABSTRACT FROM AUTHOR]

Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the diarrheal disease, cholera. Two of its primary virulence regulators, TcpP and ToxR, are localized in the inner membrane. TcpP is encoded on the Vibrio Pathogenicity Island (VPI), a horizontally acquired mobile genetic element, and functions primarily in virulence gene regulation. TcpP has been shown to undergo regulated intramembrane proteolysis (RIP) in response to environmental conditions that are unfavorable for virulence gene expression. ToxR is encoded in the ancestral genome and is present in non-pathogenic strains of V. cholerae, indicating it has roles outside of the human host. In this study, we show that ToxR undergoes RIP in V. cholerae in response to nutrient limitation at alkaline pH, a condition that occurs during the stationary phase of growth. This process involves the site-2 protease RseP (YaeL), and is dependent upon the RpoE-mediated periplasmic stress response, as deletion mutants for the genes encoding these two proteins cannot proteolyze ToxR under nutrient limitation at alkaline pH. We determined that the loss of ToxR, genetically or by proteolysis, is associated with entry of V. cholerae into a dormant state in which the bacterium is normally found in the aquatic environment called viable but nonculturable (VBNC). Strains that can proteolyze ToxR, or do not encode it, lose culturability, experience a change in morphology associated with cells in VBNC, yet remain viable under nutrient limitation at alkaline pH. On the other hand, mutant strains that cannot proteolyze ToxR remain culturable and maintain the morphology of cells in an active state of growth. Overall, our findings provide a link between the proteolysis of a virulence regulator and the entry of a pathogen into an environmentally persistent state. [ABSTRACT FROM AUTHOR]

This study demonstrates that Amblyomma americanum (Aam) constitutively and ubiquitously expresses the long (L) and short (S) putative acidic chitinases (Ach) that are distinguished by a 210 base pair (bp) deletion in AamAch-S. Full-length AamAch-L and AamAch- S cDNA are 1959 and 1718 bp long, containing 1332 and 1104 bp open reading frames that code for 443 and 367 amino acid residues proteins with the former predicted to be extracellular and the latter intracellular. Both AamAch-L and AamAch-S mRNA are expressed in multiple organs as revealed by qualitative RT-PCR analysis. Furthermore, quantitative reverse transcription polymerase chain reaction analysis revealed that AamAch-L mRNA was downregulated in the mid-gut, but was unchanged in the salivary gland and in other organs in response to feeding. Of significant interest, AamAch-L and/or AamAch-S functions are probably associated with formation and/or maintenance of stability of A. americanum tick cement cone. Dual RNA interference silencing of AamAch-L and/or AamAch-S mRNA caused ticks to loosely attach onto host skin as suggested by bleeding around tick mouthparts and ticks detaching off host skin with a light touch. AamAch-L may apparently encode an inactive chitinase as indicated by Pichia pastoris-expressed recombinant AamAch-L failing to hydrolyse chitinase substrates. Unpublished related work in our laboratory, and published work by others that found AamAch-L in tick saliva, suggest that native AamAch-L is a non-specific immunoglobulin binding tick saliva protein in that rAamAch-L nonspecifically bound rabbit, bovine and chicken non-immune sera. We discuss findings in this study with reference to advancing knowledge on tick feeding physiology. [ABSTRACT FROM AUTHOR]

Background Multiple tick saliva proteins, the majority of which are unknown, confer tick resistance in repeatedly infested animals. The objective of this study was to identify the 24-48 h fed Amblyomma americanum tick saliva immuno-proteome. The 24-48 h tick-feeding phase is critical to tick parasitism as it precedes important events in tick biology, blood meal feeding and disease agent transmission. Fed male, 24 and 96 h fed female phage display cDNA expression libraries were biopanned using rabbit antibodies to 24 and 48 h fed A. americanum female tick saliva proteins. Biopanned immuno-cDNA libraries were subjected to next generation sequencing, de novo assembly, and bioinformatic analysis. Results More than 800 transcripts that code for 24-48 h fed A. americanum immuno-proteins are described. Of the 895 immuno-proteins, 52% (464/895) were provisionally identified based on matches in GenBank. Of these, ∼19% (86/464) show high level of identity to other tick hypothetical proteins, and the rest include putative proteases (serine, cysteine, leukotriene A- 4 hydrolase, carboxypeptidases, and metalloproteases), protease inhibitors (serine and cysteine protease inhibitors, tick carboxypeptidase inhibitor), and transporters and/or ligand binding proteins (histamine binding/lipocalin, fatty acid binding, calreticulin, hemelipoprotein, IgG binding protein, ferritin, insulin-like growth factor binding proteins, and evasin). Others include enzymes (glutathione transferase, cytochrome oxidase, protein disulfide isomerase), ribosomal proteins, and those of miscellaneous functions (histamine release factor, selenoproteins, tetraspanin, defensin, heat shock proteins). Conclusions Data here demonstrate that A. americanum secretes a complex cocktail of immunogenic tick saliva proteins during the first 24-48 h of feeding. Of significance, previously validated immunogenic tick saliva proteins including AV422 protein, calreticulin, histamine release factor, histamine binding/lipocalins, selenoproteins, and paramyosin were identified in this screen, supporting the specificity of the approach in this study. While descriptive, this study opens opportunities for in-depth tick feeding physiology studies. [ABSTRACT FROM AUTHOR]

Highlights: [•] Ixodes scapularis (Ixsc) serpin (S) 1E1 is injected into the host during tick feeding. [•] Recombinant (r) IxscS-1E1 is an inhibitor of thrombin and trypsin. [•] rIxscS-1E1 inhibited platelet aggregation function in a dose-responsive manner. [•] rIxscS-1E1 delayed prevented fibrin clot formation in a dose-responsive manner. [ABSTRACT FROM AUTHOR]

The article presents a study in which a reactive hot melt adhesive (RHMA) consisting of thermoplastic polyurethane (TPU) was modified with sodium montmorillonite (Na-MMT) intercalated with poly(ethylene glycol) (PEG). Their effects on the adhesion, rheological, and mechanical properties of the RHMA were examined. It was found that Na-MMT/PEG effectively reinforced the RHMA.

Objective. The objective of this study is to evaluate transfection efficiency and safety for gene delivery by sonoporation in comparison with cationic polymer gene carrier branched polyethylenimine (BPEI). Methods. The cDNA expressing VEGF165 was cloned under chicken β-actin promoter. The plasmid DNA was transfected into the CHO, HEK293, and NIH3T3 cells using microbubble-based sonoporation and BPEI (25 kDa) under various conditions. Enzyme-linked immunosorbent assay (ELISA) was used to determine the expressed protein level. Cytotoxicities of transfection methods were compared by Cell Counting Kit-8. Results. At 1 MHz intensity, transfection efficiency of sonoporation was enhanced by microbubble concentration with no detrimental effects. By contrast, BPEI exacerbated cell viability, despite its high transgene expression efficiency. Conclusion. Sonoporation gene therapy might be the safest technique to be used in actual clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: There are no known case reports of hepatic steatosis caused by oral fluoropyrimidines such as capecitabine. With increasing use of capecitabine since its approval for the treatment of metastatic colon cancer in 2001, and more recently for adjuvant treatment of colon cancer and treatment of metastatic breast cancer, we can anticipate increased recognition of potential toxicities associated with this 5-fluorouracil derivative.Case Presentation: We report the case of a 74-year-old Armenian woman who received capecitabine as adjuvant treatment for colon cancer and subsequently developed abnormal liver biochemical tests and radiographic findings in keeping with hepatic steatosis. There was complete reversal of liver enzyme abnormalities with discontinuation of the drug and this patient represents a case of reversible liver injury due to capecitabine.Conclusion: In this original case report, capecitabine use was associated with hepatic steatosis. It is important for clinicians to recognize and monitor for this potential toxicity, which may be a cause of abnormal liver enzymes in this patient population. [ABSTRACT FROM AUTHOR]