244 research outputs found

    Fibrinogen-γ proteolysis and solubility dynamics during apoptotic mouse liver injury: Heparin prevents and treats liver damage

    Full text link
    Fas ligand (FasL)-mediated hepatocyte apoptosis occurs in the context of acute liver injury that can be accompanied by intravascular coagulation (IC). We tested the hypothesis that analysis of selected protein fractions from livers undergoing apoptosis will shed light on mechanisms that are involved in liver injury that might be amenable to intervention. Proteomic analysis of the major insoluble liver proteins after FasL exposure for 4-5 hours identified fibrinogen-γ (FIB-γ) dimers and FIB-γ–containing high molecular mass complexes among the major insoluble proteins visible via Coomassie blue staining. Presence of the FIB-γ–containing products was confirmed using FIB-γ–specific antibodies. The FIB-γ–containing products partition selectively and quantitatively into the liver parenchyma after inducing apoptosis. Similar formation of FIB-γ products occurs after acetaminophen administration. The observed intrahepatic IC raised the possibility that heparin therapy may ameliorate FasL-mediated liver injury. Notably, heparin administration in mice 4 hours before or up to 2 hours after FasL injection resulted in a dramatic reduction of liver injury—including liver hemorrhage, serum alanine aminotransferase, caspase activation, and liver apoptosis—compared with heparin-untreated mice. Heparin did not directly interfere with FasL-induced apoptosis in isolated hepatocytes, and heparin-treated mice survived the FasL-induced liver injury longer compared with heparin-untreated animals. There was a sharp, near-simultaneous rise in FasL-induced intrahepatic apoptosis and coagulation, with IC remaining stable while apoptosis continued to increase. Conclusion: Formation of FIB-γ dimers and their high molecular mass products are readily detectable within the liver during mouse apoptotic liver injury. Heparin provides a potential therapeutic modality, because it not only prevents extensive FasL-related liver injury but also limits the extent of injury if given at early stages of injury exposure. (H EPATOLOGY 2011;)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83742/1/24203_ftp.pd

    Learning Management System Built Using the MERN Stack

    Get PDF
    Web based applications play a main role in our day-to-day life and therefore, it is important to ensure the quality and reliability of web applications. With the sudden increase in use of web based applications for online and distant learning, it is important to address existing issues in current Learning Management Systems (LMS), so that users can benefit from a better, uninterrupted learning experience. This work mainly contributes to understanding how the MERN stack can be efficiently used in building a reliable and secure LMS that will provide its services free of charge so that students are provided with a free and uninterrupted learning experience. An LMS that is equipped with user handling functionality, managing courses and course materials, and maintaining a library, has been the focus of the study that resulted in producing this paper. The work also includes reasoning as to why the MERN stack was selected for developing the proposed system

    Determinants of online shopping among tertiary students in Ghana: An extended technology acceptance model

    Get PDF
    The increasing penetration rate of the internet and technology in the world is quickly promoting online shopping. This has been fueled by growing innovations in the telecommunication and financial sector in an attempt to depeen financial inclusion. Innovations such as mobile money payments systems by mobile telephony companies have contributed to the continuous growth in online shopping amidst and the new generation of consumers who desire richer experiences. This study sought to identify the determinants of online shopping behaviour among tertiary students through the lens of the Technology Acceptance Model (TAM). The study proposed a revised TAM that integrated perceived cost and perceived risk to investigate what determined students online shopping intention and actual use. The survey involved a sample of 580 undergraduate students. The statistical technique used was Structural Equation Modelling-Partial Least Squares (SEM-PLS). The results showed that effect of ease of use on usefulness was very significant as same has been predicted by the Technology Acceptance Model. Among the independent variables, perceived cost (PC) was found to be the most significant factor affecting actual use (AU) of online shopping among students, nonetheless, perceived cost (PC) had no significant effect on purchase intention (PI). Perceived risk (PR) had no significant effect on actual use (AU) however, had a significant effect on purchase intention (PI). The study recommends online sellers to make online shopping efficient and less costive with assured safety and security of transactions as well as the product itself. A set of shopping platform could even be created specifically to give discounts and other offers to students. It also recommends future studies to employ additional determining factors such as the type of product/service, convenience and personal/demographic and geographic factors as influential to students’ online purchasing behaviour. © 2019, © 2019 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license

    Vendor-based restrictions on pesticide sales to prevent pesticide self-poisoning - a pilot study

    Get PDF
    Abstract Background In South Asia, up to 20% of people ingesting pesticides for self-poisoning purchase the pesticide from a shop with the sole intention of self-harm. Individuals who are intoxicated with alcohol and/or non-farmers represent 72% of such high-risk individuals. We aimed to test the feasibility and acceptability of vendor-based restrictions on pesticide sales for such high-risk individuals. Methods We conducted a pilot study in 14 (rural = 7, urban = 7) pesticide shops in Anuradhapura District of Sri Lanka. A two-hour training program was delivered to 28 pesticide vendors; the aim of the training was to help vendors recognize and respond to customers at high risk of pesticide self-poisoning. Knowledge and attitudes of vendors towards preventing access to pesticides for self-poisoning at baseline and in a three month follow-up was evaluated by questionnaire. Vendors were interviewed to explore the practice skills taught in the training and their assessment of the program. Results The scores of knowledge and attitudes of the vendors significantly increased by 23% (95% CI 15%–32%, p < 0.001) and by 16% (95% CI 9%–23%, p < 0.001) respectively in the follow-up. Fifteen (60%) vendors reported refusing sell pesticides to a high-risk person (non-farmer or intoxicated person) in the follow-up compared to three (12%) at baseline. Vendors reported that they were aware from community feedback that they had prevented at least seven suicide attempts. On four identified occasions, vendors in urban shops had been unable to recognize the self-harming intention of customers who then ingested the pesticide. Only 2 (8%) vendors were dissatisfied with the training and 23 (92%) said they would recommend it to other vendors. Conclusions Our study suggests that vendor-based sales restriction in regions with high rates of self-poisoning has the potential to reduce access to pesticides for self-poisoning. A large-scale study of the effectiveness and sustainability of this approach is needed

    Evaluation of acceptability and use of lockable storage devices for pesticides in Sri Lanka that might assist in prevention of self-poisoning

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Self-poisoning with pesticides is a major reason for high suicide rates in rural areas of many developing countries. Safer storage of pesticides may be one means of prevention. We have conducted a study to assess the acceptability and use of lockable boxes for storing pesticides in rural Sri Lanka.</p> <p>Methods</p> <p>Four hundred lockable metal storage boxes were given to farming households, 100 in each of four villages. Assessment interviews were conducted by Sumithrayo (NGO) field workers immediately after boxes were supplied (T1), 11 – 14 weeks later (T2), 30 weeks later (T3), and 18 months later (T4). Data on suicide and self-harm were collected from local police and hospitals.</p> <p>Results</p> <p>At T1 only 1.8% (7/396) of households reported locking up pesticides, 72.5% (279/385) easy access to pesticides for adults and 50.4% (195/387) easy access for children. At T3 most informants in households using pesticides reported using the box all (82.3%, 298/362) or most of the time (7.2%, 26/362). Informants usually reported always locking the box (92.8%, 336/362) and most boxes were locked on inspection (93.6%, 339/362). By T4 there was some reduction in reporting that the box was kept locked all of the time (75.2%, 267/355) and the box being locked on inspection (73.8%, 262/355). Easy child access to the key was reported in relatively few households (10.7% at T4), although interviewers judged that this was possible in rather more (20.6%). Most informants regarded the box as useful (100% at T3 and 99.4% at T4), with convenience for storage, security, avoiding wastage, and protection of children being major factors. A message on the box about how to deal with bad feelings and the importance of safer storage was well received. The locks had been broken or the key lost in a few households.</p> <p>Conclusion</p> <p>Introduction of lockable boxes for storing pesticides to farming households in Sri Lanka appeared to be acceptable. Most households used the boxes responsibly, although there was some decline in the proper usage over time. A large-scale trial of lockable storage devices in farming households in rural areas as a means of prevention of suicide and accidental poisoning is now indicated.</p

    Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

    Get PDF
    Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

    Equilibrium molecular thermodynamics from Kirkwood sampling.

    Get PDF
    We present two methods for barrierless equilibrium sampling of molecular systems based on the recently proposed Kirkwood method (J. Chem. Phys. 2009, 130, 134102). Kirkwood sampling employs low-order correlations among internal coordinates of a molecule for random (or non-Markovian) sampling of the high dimensional conformational space. This is a geometrical sampling method independent of the potential energy surface. The first method is a variant of biased Monte Carlo, where Kirkwood sampling is used for generating trial Monte Carlo moves. Using this method, equilibrium distributions corresponding to different temperatures and potential energy functions can be generated from a given set of low-order correlations. Since Kirkwood samples are generated independently, this method is ideally suited for massively parallel distributed computing. The second approach is a variant of reservoir replica exchange, where Kirkwood sampling is used to construct a reservoir of conformations, which exchanges conformations with the replicas performing equilibrium sampling corresponding to different thermodynamic states. Coupling with the Kirkwood reservoir enhances sampling by facilitating global jumps in the conformational space. The efficiency of both methods depends on the overlap of the Kirkwood distribution with the target equilibrium distribution. We present proof-of-concept results for a model nine-atom linear molecule and alanine dipeptide.This research was funded by the European Research Council and EPSRC grant EP/I001352/1. Y.O. was supported, in part, by the JSPS Grant-in-Aid for Scientific Research on Innovative Areas (“Dynamical Ordering and Integrated Functions”).This is the final published version. It first appeared at http://pubs.acs.org/doi/abs/10.1021/acs.jpcb.5b01800

    Molecular dynamics simulation studies of the interactions between ionic liquids and amino acids in aqueous solution

    Get PDF
    Although the understanding of the influence of ionic liquids (ILs) on the solubility behavior of biomolecules in aqueous solutions is relevant for the design and optimization of novel biotechnological processes, the underlying molecular-level mechanisms are not yet consensual or clearly elucidated. In order to contribute to the understanding of the molecular interactions established between amino acids and ILs in aqueous media, classical molecular dynamics (MD) simulations were performed for aqueous solutions of five amino acids with different structural characteristics (glycine, alanine, valine, isoleucine, and glutamic acid) in the presence of 1-butyl-3-methylimidazolium bis(trifluoromethyl)sulfonyl imide. The results from MD simulations enable to relate the properties of the amino acids, namely their hydrophobicity, to the type and strength of their interactions with ILs in aqueous solutions and provide an explanation for the direction and magnitude of the solubility phenomena observed in [IL + amino acid + water] systems by a mechanism governed by a balance between competitive interactions of the IL cation, IL anion, and water with the amino acids

    A New bis(rhodamine)-Based Fluorescent Chemosensor for Fe3+

    Get PDF
    A new bis(rhodamine)-based fluorescent probe 4 was synthesized, and it exhibited high selectivity for Fe3+ over other commonly coexistent metal ions in both 50% ethanol and Tris–HCl buffer. Upon the addition of Fe3+, the spirocyclic ring of 4 was opened and a significant enhancement of visible color and fluorescence in the range of 500–600 nm was observed
    corecore