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Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.  相似文献   
63.
This prospective study evaluated seroepidemiologic features of canine respiratory coronavirus (CRCoV), canine parainfluenza virus (CPIV), and Bordetella bronchiseptica infections in dogs in an urban humane shelter and in rural/small community dog populations in western Canada. Seroprevalence of CRCoV and CPIV was low compared with other countries; seroprevalence of B. bronchiseptica was moderate to high in most populations examined. Rural dogs were 0.421 times (P ≤ 0.0001) less likely to be positive for CRCoV than dogs admitted to the shelter. There were no statistical differences in prevalence of antibodies to B. bronchiseptica and CPIV between urban and rural populations. Dogs from Fort Resolution, NWT were significantly (P < 0.05) less likely to have moderate or high antibody titers to the 3 agents than dogs in the shelter. Seroconversion to CRCoV was common in dogs in the shelter, but was not associated (P = 0.18) with respiratory disease. Antibodies to CRCoV, CPIV, or B. bronchiseptica on arrival were not significantly (P > 0.05) associated with disease-sparing after entry into the shelter.  相似文献   
64.
The global cycle of mercury (Hg) is reasonably well-understood, as are some of the natural and anthropogenic sources of Hg to the atmosphere. Less well understood are the regional and local characteristics of Hg deposition and subsequent watershed-scale transport, important parameters for assessing human risk to various avenues of Hg exposure. This study employed a two-part strategy for understanding coupled deposition and transport processes in central Indiana (USA), including Indianapolis, a typical large city with multiple coal-fired electric utilities and other Hg emission sources. A spatial analysis of Hg concentrations in surface soils revealed elevated Hg proximal to many of the large emission sources, with a distribution aligned along a southwest-northeast axis corresponding to the mean wind direction in this region. This soil distribution suggests some local depositional impact from local utilities, with wind modification affecting the regional pattern. Post-depositional transport of Hg was assessed using a series of streambank sampling arrays as the White River and various tributaries travelled through the urban core of Indianapolis. Streambank sediments had peak Hg concentrations in the urban core, where several local sources are present and where a number of subwatersheds join the main trunk of the White River, suggesting local emission and/or rapid Hg transport from urban subwatersheds due to their relatively high proportion of impervious surfaces. High Hg values persist in White River sediments into rural areas tens of kilometers south of Indianapolis, raising concerns for anglers collecting fish in this apparently “pristine” environment.  相似文献   
65.
Certain breeds are known to be overrepresented among mast cell tumor (MCT) patients, but other risk factors have not been evaluated. This study presents results from a case-control study of 252 dogs with grade 2 or grade 3 cutaneous MCT. Increased risk for MCT development was found in spayed females (adjusted odds ratio [OR], 4.11), boxers (adjusted OR, 6.09), Labrador retrievers (adjusted OR, 3.95), pugs (adjusted OR, 3.17), golden retrievers (adjusted OR, 2.12), the mastiff and terrier phylogenetic cluster (adjusted OR, 3.19), and breeds classified as large (adjusted OR, 2.10) or giant (adjusted OR, 5.44). Additional studies are needed to evaluate the role of these and other potential risk factors in MCT development.  相似文献   
66.
Intranasal tumors of dogs and cats pose a diagnostic and therapeutic challenge for small animal practitioners. Multiple nasal biopsy techniques have been described in the past. This report describes a simplified flushing technique to biopsy and debulk nasal tumors, which often also results in immediate clinical relief for the patient. Based on the results of this retrospective study, the authors recommend high-pressure saline hydropulsion as a minimally invasive diagnostic, and potentially therapeutic, technique for nasal tumors in dogs and cats.  相似文献   
67.
OBJECTIVE: To determine whether single-fraction and combination modified-live bovine respiratory syncytial virus (BRSV) vaccines commercially licensed for parenteral administration could stimulate protective immunity in calves after intranasal administration. DESIGN: Randomized controlled trial. ANIMALS: 39 calves. PROCEDURES: Calves were separated from dams at birth, fed colostrum with a minimal concentration of antibodies against BRSV, and maintained in isolation. In 2 preliminary experiments, 9-week-old calves received 1 (n = 3) or 2 (3) doses of a single-component, modified-live BRSV vaccine or no vaccine (8 control calves in each experiment), and were challenged with BRSV 21 days after vaccination. In a third experiment, 2-week-old calves received combination modified-live virus (MLV) vaccines with or without BRSV and calves were challenged with BRSV 8 days later. Calves were euthanized, and lung lesions were measured. Immune responses, including serum and nasal antibody and nasal interferon-alpha concentrations, were assessed. RESULTS: BRSV challenge induced signs of severe clinical respiratory tract disease, including death and pulmonary lesions in unvaccinated calves and in calves that received a combination viral vaccine without BRSV. Pulmonary lesions were significantly less severe in BRSV-challenged calves that received single or combination BRSV vaccines. The proportion of calves that shed virus and the peak virus titer was decreased, compared with control calves. Protection was associated with mucosal IgA antibody responses after challenge. CONCLUSIONS AND CLINICAL RELEVANCE: Single and combination BRSV vaccines administered intranasally provided clinical protection and sparing of pulmonary tissue similar to that detected in response to parenteral delivery of combination MLV and inactivated BRSV vaccines previously assessed in the same challenge model.  相似文献   
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69.
Orthopaedic disorders are commonly encountered in equine veterinary medicine, and non-steroidal anti-inflammatory drugs (NSAIDs) play an important role in the management of many equine orthopaedic disorders. There are multiple NSAIDs available for use in horses, including both non-selective and selective NSAIDS, and the body of literature evaluating the efficacy of these medications, their effects on normal and inflamed musculoskeletal tissues, and their side effects is broad. This review aims to summarise the current literature on the use of NSAIDs for equine orthopaedic disorders and examines new and future avenues for the management of inflammation in equine orthopaedics.  相似文献   
70.
Two cadmium-resistant bacteria, Ralstonia sp. TAK1 and Arthrobacter sp. TM6, produced exopolymers that promoted cadmium solubilization in contaminated soil. The enhancement of cadmium uptake and accumulation in a monocot (Vetiveria nemoralis, vetiver grass) and a dicot (Ocimum gratissimum, African basil) was investigated in a greenhouse study. Compared with the uninoculated control, Ralstonia sp. TAK1 and Arthrobacter sp. TM6 increased cadmium accumulation in the roots and shoots of V. nemoralis. These cadmium-resistant bacteria increased the cadmium content of whole V. nemoralis plants similarly to ethylenediaminetetraacetic acid (EDTA) treatment alone. In contrast, only Arthrobacter sp. TM6 enhanced cadmium accumulation in the roots and shoots of O. gratissimum. The highest cadmium content of whole O. gratissimum plants was observed when the plant was treated with EDTA following treatment with Arthrobacter sp. TM6. The phytoextraction coefficient and translocation factor (TF) of bacteria-inoculated V. nemoralis were higher than those of O. gratissimum. Arthrobacter sp. TM6 increased the phytoextraction coefficients and TFs in V. nemoralis and O. gratissimum. These results indicate that Arthrobacter sp. TM6 and both tested plant species promote cadmium phytoextraction in contaminated soil.  相似文献   
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