The intentional use of Bacillus anthracis, the etiological agent of anthrax, as a bioterrorist weapon in late 2001 made our society acutely aware of the importance of developing, testing, and stockpiling adequate countermeasures against biological attacks. Biodefense vaccines are an important component of our arsenal to be used during a biological attack. However, most of the agents considered significant threats either have been eradicated or rarely infect humans alive today. As such, vaccine efficacy cannot be determined in human clinical trials but must be extrapolated from experimental animal models. This article reviews the efficacy and immunogenicity of human anthrax vaccines in well-defined animal models and the progress toward developing a rugged immunologic correlate of protection. The ongoing evaluation of human anthrax vaccines will be dependent on animal efficacy data in the absence of human efficacy data for licensure by the U.S. Food and Drug Administration

Routine detection of porcine epidemic diarrhea virus (PEDV) is currently limited to RT-PCR but this test cannot distinguish between viable and inactivated virus. We evaluated the capability of disinfectants to both inactivate PEDV and sufficiently damage viral RNA beyond RT-PCR detection. Five classes of disinfectants (phenol, quaternary ammonium compound, sodium hypochlorite, oxidizing agent, and quaternary ammonium/glutaraldehyde combination) were evaluated in vitro at varying concentrations, both in the presence and absence of swine feces, and at three different temperatures. No infectious PEDV was recovered after treatment with evaluated disinfectants. Additionally, all tested disinfectants except for 0.17% sodium hypochlorite dramatically reduced qRT-PCR values. However, no disinfectants eliminated RT-PCR detection of PEDV across all replicates; although, 0.52%, 1.03% and 2.06% solutions of sodium hypochlorite and 0.5% oxidizing agent did intermittently produce RT-PCR negatives. To simulate field conditions in a second aim, PEDV was applied to pitted aluminum coupons, which were then treated with either 2.06% sodium hypochlorite or 0.5% oxidizing agent. Post-treatment surface swabs of the coupons tested RT-PCR positive but were not infectious to cultured cells or naïve pigs. Ultimately, viable PEDV was not detected following application of each of the tested disinfectants, however in most cases RT-PCR detection of viral RNA remained. RT-PCR detection of PEDV is likely even after disinfection with many commercially available disinfectants.

Metastasis is the primary cause of death in breast cancer patients, yet there are challenges to modeling this process in vivo. The goal of this study was to analyze the effects of injection site on tumor growth and metastasis and gene expression of breast cancer cells in vivo using the MMTV-PymT breast cancer model (Met-1 cells). Met-1 cells were injected into 5 sites (subcutaneous, mammary fat pad, tail vein, intracardiac, and intratibial), and tumors and metastases were monitored using bioluminescent imaging and confirmed with gross necropsy and histopathology. Met-1 tumors were analyzed based on morphology and changes in gene expression in each tissue microenvironment. There were 6 permissible sites of Met-1 tumor growth (mammary gland, subcutis, lung, adrenal gland, ovary, bone). Met-1 cells grew faster in the subcutis compared to mammary fat pad tumors (highest Ki-67 index). Morphologic differences were evident in each tumor microenvironment. Finally, 7 genes were differentially expressed in the Met-1 tumors in the 6 sites of growth or metastasis. This investigation demonstrates that breast cancer progression and metastasis are regulated by not only the tumor cells but also the experimental model and unique molecular signals from the tumor microenvironment.

The features of gliomatosis cerebri involving the brainstem and cerebellum in a 3-year-old dog are described. In magnetic resonance (MR) images, there was diffuse loss of the cerebellar folia and cerebellar gray and white matter contrast. Multiple illdefined T2-hyperintensities were present in the cerebellar parenchyma. A poorly defined, T2-hyperintense mass effect was present ventral to the pons and rostral medulla. No contrast enhancement was noted. Cerebrospinal fluid (CSF) was normal. Postmortem examination was consistent with gliomatosis cerebri, based on compatible histopathology and immunohistochemical findings. Although rare, gliomatosis cerebri should be included as a differential for diffuse infiltrative central nervous system (CNS) lesions.

The emergence of additive manufacturing has afforded the ability to fabricate intricate, high resolution, and patient‐specific polymeric implants. However, the availability of biocompatible resins with tunable resorption profiles remains a significant hurdle to clinical translation. In this study, 3D scaffolds are fabricated via stereolithographic cDLP printing of poly(propylene fumarate) (PPF) and assessed for bone regeneration in a rat critical‐sized cranial defect model. Scaffolds are printed with two different molecular mass resin formulations (1000 and 1900 Da) with narrow molecular mass distributions and implanted to determine if these polymer characteristics influence scaffold resorption and bone regeneration in vivo. X‐ray microcomputed tomography (µ‐CT) data reveal that at 4 weeks the lower molecular mass polymer degrades faster than the higher molecular mass PPF and thus more new bone is able to infiltrate the defect. However, at 12 weeks, the regenerated bone volume of the 1900 Da formulation is nearly equivalent to the lower molecular mass 1000 Da formulation. Significantly, lamellar bone bridges the defect at 12 weeks with both PPF formulations and there is no indication of an acute inflammatory response.

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IntroductionHuman T lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL)/lymphoma and is strongly associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a variety of other immune-mediated disorders. 1-3 Despite a strong immune response against HTLV-1, the virus typically is maintained as a persistent infection throughout the lifetime of infected subjects. Critical immunologic parameters, including efficient cytotoxic T-cell responses against HTLV-1-expressing cells, determine viral loads throughout the course of infection and are linked to disease outcomes. 4,5 There have been several reports focused on the effect of immune suppression on pathogenesis of HTLV-1 disease. 6-9 HTLV-1-infected patients who are concurrently treated with immunosuppressive drugs, typically for organ or bone marrow transplantation procedures, often exhibit an accelerated or altered course for the development of HTLV-1-associated diseases. [10][11][12][13] These patients typically receive drugs such as cyclosporine A (CsA) and tacrolimus (FK-506) to prevent organ graft rejection. There are limited reports of the effects of immune suppression on early HTLV-1 infection because of the lack of clinical materials and inability to simulate the initial exposure of HTLV-1 infection on humans.We have used the rabbit model of HTLV-1 infection, in part, because of the ease and consistency of transmission of the viral infection in this species. Rabbits have been used to confirm routes of transmission for the virus infection, monitor sequential immune responses against HTLV-1 infection, test vaccine approaches, and determine virus-host relationships during the course of infection. [14][15][16][17][18] Our current study reported in this work tested the effects of immune suppression on the early spread of HTLV-1 infection in an established rabbit model. New Zealand white rabbits were divided into groups and treated with 10 mg/kg CsA, 20 mg/kg CsA, or saline vehicle control before infection by intravenous inoculation of HTLV-1-infected rabbit cells. Another group of rabbits was treated with 20 mg/kg CsA 1 week after HTLV-1 infection. Plasma CsA concentrations were monitored to ensure that therapeutic concentrations of the drug were obtained during treatment periods. Immune suppression was monitored in the rabbits by measuring lymphocyte proliferation to a recall antigen and mitogen stimulation, as well as flow cytometry and hematologic analysis. HTLV-1 viral expression in rabbits was monitored by testing ex vivo lymphocyte HTLV-1 p19 production, serologic parameters, and proviral loads from peripheral blood lymphocyte cultures. CsA treatment before HTLV-1 infection enhanced early viral expression compared with untreated HTLV-1-infected rabbits, and did alter long-term viral expression parameters. However, CsA treatment 1 week after infection diminished HTLV-1 expression throughout the 10-week study course. Our data indicate that immunologic control during early virus exposure determine...

Outdoor housing and ultraviolet exposure, breed, and chronic superficial keratitis were all suspected as contributing factors to the development of a primary corneal hemangiosarcoma. Surgical removal and postoperative treatment for chronic superficial keratitis provided effective therapy.