971 research outputs found
Ex vivo rabbit and human corneas as models for bacterial and fungal keratitis.
PURPOSE: In the study of microbial keratitis, in vivo animal models often require a large number of animals, and in vitro monolayer cell culture does not maintain the three-dimensional structure of the tissues or cell-to-cell communication of in vivo models. Here, we propose reproducible ex vivo models of single- and dual-infection keratitis as an alternative to in vivo and in vitro models. METHODS: Excised rabbit and human corneoscleral rims maintained in organ culture were infected using 10(8) cells of Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans or Fusarium solani. The infection was introduced by wounding with a scalpel and exposing corneas to the microbial suspension or by intrastromal injection. Post-inoculation, corneas were maintained for 24 and 48 h at 37 °C. After incubation, corneas were either homogenised to determine colony-forming units (CFU)/cornea or processed for histological examination using routine staining methods. Single- and mixed-species infections were compared. RESULTS: We observed a significant increase in CFU after 48 h compared to 24 h with S. aureus and P. aeruginosa. However, no such increase was observed in corneas infected with C. albicans or F. solani. The injection method yielded an approximately two- to 100-fold increase (p < 0.05) in the majority of organisms from infected corneas. Histology of the scalpel-wounded and injection models indicated extensive infiltration of P. aeruginosa throughout the entire cornea, with less infiltration observed for S. aureus, C. albicans and F. solani. The models also supported dual infections. CONCLUSIONS: Both scalpel wounding and injection methods are suitable for inducing infection of ex vivo rabbit and human cornea models. These simple and reproducible models will be useful as an alternative to in vitro and in vivo models for investigating the detection and treatment of microbial keratitis, particularly when this might be due to two infective organisms
The limits of relational governance: Sales force strategies in the U.S. medical device industry
Research Summary: We explore how inter-organizational relationships shape firm boundary decisions. Using data on 545 U.S. medical device manufacturers’ product portfolios and sales governance choices (i.e., internal or external sales forces) from 1983 to 1996, we find relational capital between manufacturers and external sales forces influences future firm boundary decisions. Relational capital lowers the likelihood of integrating the sales function, but only when firms remain focused on the same product market. Further, launching an innovative product has a nuanced effect. For firms lacking relational capital, innovation increases the likelihood of sales integration. This pattern reverses as relational capital accumulates, but only when innovations are in the firm’s existing focal product market. Our findings suggest important
limits on the effect of relational governance on firm strategy.
Managerial Abstract: Choosing between in-house or external sales is a key strategic decision. In the medical device industry, this decision is particularly important because sales people are conduits between R&D and customers. For firms who initially choose external sales, the tradeoff between maintaining existing links (via external sales) and developing new, direct relationships (by bringing sales in-house) can change significantly as product portfolios change. Analyzing 545 U.S. medical device manufacturers from 1983 to 1996, we find that existing relationships with external sales forces reduce the likelihood of bringing sales in-house, but only
when firms remain in the same product market, such as orthopedic implants. When firms launch products in new markets, especially innovations, they are more likely to bring sales in-house
Economic value for the trait tick count in Brangus cattle.
Profitability of a beef cattle system may be significantly reduced by the effects of tick (Rhipicephalus (Boophilus) microplus).IMAS. PĂ´ster 45209
A methodology for the production of microfabricated electrospun membranes for the creation of new skin regeneration models
The continual renewal of the epidermis is thought to be related to the presence of populations of epidermal stem cells residing in physically protected microenvironments (rete ridges) directly influenced by the presence of mesenchymal fibroblasts. Current skin in vitro models do acknowledge the influence of stromal fibroblasts in skin reorganisation but the study of the effect of the rete ridge-microenvironment on epidermal renewal still remains a rich topic for exploration. We suggest there is a need for the development of new in vitro models in which to study epithelial stem cell behaviour prior to translating these models into the design of new cell-free biomaterial devices for skin reconstruction.
In this study we aimed to develop new prototype epidermal-like layers containing pseudo-rete ridge structures for studying the effect of topographical cues on epithelial cell behaviour. The models were designed using a range of 3D electrospun microfabricated scaffolds. This was achieved via the utilisation of polyethylene glycol diacrylate (PEDGA) to produce a reusable template over which Poly (3-hydrroxybutyrate-co-3-hydroxyvalerate) (PHBV) was electrospun. Initial investigations studied the behaviour of keratinocytes cultured on models using plain scaffolds (without the presence of intricate topography) versus keratinocytes cultured on scaffolds containing micro-features
Generation and use of functionalised hydrogels that can rapidly sample infected surfaces
This paper outlined our method for developing polymer-linked contact lens type materials for rapid detection and differentiation of Gram-positive, Gram-negative bacteria and fungi in infected corneas. It can be applied to both model synthetic or ex-vivo corneal models and has been successfully trialed in an initial efficacy tested animal study. First a hydrogel substrate for the swab material is selected, we have demonstrated selective swabs using a glycerol monomethacrylate hydrogel. Alternatively any commercial material with carboxylic acid functional groups is suitable but risks nonspecific adhesion. This is then functionalised via use of N-hydroxysuccinimide reaction with amine groups on the specified highly branched polymer ligand (either individually gram negative, gram positive or fungal binding polymers or a combination of all three can be employed for desired sensing application). The hydrogel is then cut into swabs suitable for sampling, used, and then the presence of gram positive, game negative and fungi are disclosed by the sequential addition of dyes (fluorescent vancomycin, fluorescein isothiocyanate and calcofluor white).
In summary this method presents:
Method to produce glycerol monomethacrylate hydrogels to minimize nonspecific binding
Methods of attaching pathogen binding highly branched polymers to produce selective hydrogel swabs
Method for disclosing bound pathogens to this swab using sequential dye additio
Managing local supplier networks: conflict or compromise
This paper examines conflict management in small firm networks. Informal conflict management strategies used in exchange relationships are identified and analysed. In-depth, semi-structured interviews with 22 small and medium-sized enterprise managers in an industrial district in the south-east of France are analysed. Results point to managers adopting accommodating behaviours in conflicts with clients and compromising and collaborative strategies with local partners. This research reveals the mobilization of local norms in the management of conflicts and also contributes to research concerning coopetition and the possibility that managers of small firms may both separate and integrate coopetition activities
The Tissue-Engineered Vascular Graft-Past, Present, and Future
Cardiovascular disease is the leading cause of death worldwide, with this trend predicted to continue for the foreseeable future. Common disorders are associated with the stenosis or occlusion of blood vessels. The preferred treatment for the long-term revascularization of occluded vessels is surgery utilizing vascular grafts, such as coronary artery bypass grafting and peripheral artery bypass grafting. Currently, autologous vessels such as the saphenous vein and internal thoracic artery represent the gold standard grafts for small-diameter vessels (<6 mm), outperforming synthetic alternatives. However, these vessels are of limited availability, require invasive harvest, and are often unsuitable for use. To address this, the development of a tissue-engineered vascular graft (TEVG) has been rigorously pursued. This article reviews the current state of the art of TEVGs. The various approaches being explored to generate TEVGs are described, including scaffold-based methods (using synthetic and natural polymers), the use of decellularized natural matrices, and tissue self-assembly processes, with the results of various in vivo studies, including clinical trials, highlighted. A discussion of the key areas for further investigation, including graft cell source, mechanical properties, hemodynamics, integration, and assessment in animal models, is then presented
Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial
© Cuzick et al. Open Access article distributed under the terms of CC BY.http://dx.doi.org/10.1016/S1470-2045(14)71171-
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Comparison of Heterologous Neutralizing Antibody Responses of Human Immunodeficiency Virus Type 1 (HIV-1)- and HIV-2-Infected Senegalese Patients: Distinct Patterns of Breadth and Magnitude Distinguish HIV-1 and HIV-2 Infections
Neutralizing antibody responses against heterologous isolates in human immunodeficiency virus type 1 (HIV-1) and HIV-2 infections were compared, and their relationships with established clinical markers of progression were examined. Neutralizing responses against 7 heterologous primary isolates and 1 laboratory strain were compared between 32 untreated HIV-1-infected subjects and 35 untreated HIV-2-infected subjects using a pseudotyped reporter virus assay. The breadth of the neutralizing response, defined as the proportion of panel viruses positively neutralized by patient plasma, was significantly greater among HIV-2-infected subjects than among HIV-1-infected subjects. Notably, for fully one-third of HIV-2 subjects, all viruses were effectively neutralized in our panel. Magnitudes of responses, defined as reciprocal 50% inhibitory concentration (IC(50)) titers for positive reactions, were significantly greater among HIV-1-infected subjects than among HIV-2-infected subjects. When plasma samples from HIV-1 patients were tested for cross-neutralization of HIV-2 and vice versa, we found that these intertype responses are very rare and their prevalences comparable in both HIV-1 and HIV-2 infection. The significantly higher magnitude of heterologous responses for HIV-1 compared to HIV-2 prompted us to examine associations with viremia, which is known to be significantly higher in HIV-1 infection. Importantly, there was a significant positive correlation between the IC(50) titer and viral load within both the HIV-1 and HIV-2 groups, suggesting heterologous antibodies may be driven by viral replication. We conclude that HIV-2 infection is characterized by a broad, low-magnitude intratype neutralization response, while HIV-1 is characterized by a narrower but higher-magnitude intratype response and that a significant positive association between the IC(50) titer and viremia is common to both HIV-1 and HIV-2 infections
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