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An 11-year (2007-2018) survey of epidemiological, clinical and pathological findings of horses with primary gastric rupture (PGR) was conducted. Twenty horses presented PGR, nine (45%) horses were clinically evaluated, eleven (55%) were sent dead, and all animals were necropsied. PGR contributed to a prevalence of 0.31% (9/2,868) of all equid attendances, 1.83% (9/491) of colic cases, and 4.1% (20/487) of all equid necropsies. Highly fermentable feed (n=7), gastric impaction (n=4), and perforating gastric ulcer (n=1) were the main causes of PGR; whilst eight horses presented idiopathic gastric rupture. Clinically evaluated horses were tachycardic, tachypneic, febrile, dehydrated, with increased abdominal tension, abnormal mucous membranes and reduced to absent intestinal borborygmi. Improper dietary management, such as the ingestion of low-quality roughage and highly fermentable feedstuffs were detected as the main factors associated with PGR in Midwestern Brazil. It is important to raise awareness in horse owners about proper feed management to minimize PGR.(AU)

Foi realizado um levantamento de 11 anos (2007-2018) dos achados epidemiológicos, clínicos e patológicos de equinos com ruptura gástrica primária (RGP). Vinte equinos apresentaram RGP, dos quais nove (45%) foram avaliados clinicamente e 11 (55%) foram enviados mortos, sendo todos os animais necropsiados. A RGP contribuiu com prevalência de 0,31% de todos os atendimentos de equídeos (9/2.868), 1,83% (9/491) dos casos de cólica, e 4,1% (20/487) das necropsias em equídeos. Alimentos altamente fermentáveis (n=7), compactação gástrica (n=4) e perfuração de úlcera gástrica (n=1) foram as principais causas de RGP, enquanto oito equinos tiveram ruptura gástrica idiopática. Os equinos avaliados clinicamente apresentaram-se taquicárdicos, taquipneicos, febris, desidratados, com mucosas anormais, aumento da tensão abdominal e motilidade intestinal reduzida. O manejo inadequado da dieta, como a ingestão de forragens de baixa qualidade e alimentos altamente fermentáveis, foi o principal fator de risco associado à RGP no Centro-Oeste do Brasil. É importante aumentar a conscientização dos proprietários de equinos sobre o manejo alimentar adequado para minimizar a RGP.(AU)

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Canine mammary tumours (CMTs) are the most common type of neoplasm in bitches. As in women, the presence of metastasis in regional lymph nodes is an important prognostic factor in bitches with mammary carcinomas, but the clinical significance of occult isolated tumour cells (ITCs) within lymph nodes is still undefined in this species. The effectiveness of immunohistochemistry (IHC) in identifying occult ITCs and micrometastasis (MIC) was compared with that of the conventional haematoxylin and eosin staining technique. The relationship between tumour size, histological type, histological grade and the presence of metastasis was evaluated. The overall survival (OS) of female dogs with occult mammary carcinomas and ITCs within lymph nodes was analysed. Fragments of mammary carcinoma and regional lymph nodes of 59 female dogs were also evaluated. Histological sections of mammary carcinoma and lymph node samples were studied for tumour diagnosis and lymph node samples were tested by IHC using a pan-cytokeratin antibody. It was found that 35.2% of occult ITCs and 2.8% of hidden MIC were detected when IHC was used. There was a good correlation between the size of the tumour and metastasis to the lymph nodes (P = 0.77). ITCs were observed more frequently in the medullary region (60.7%) and metastases in the cortical region (44.4%). There was no significant difference in the OS between female dogs with occult ITCs and lymph nodes without ITCs. IHC can detect occult tumour cells in lymph nodes that are negative by histopathological examination. Female dogs with nodal ITCs do not have lower survival.

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Nanoscale focused ion beams (FIBs) represent one of the most useful tools in nanotechnology, enabling nanofabrication via milling and gas-assisted deposition, microscopy and microanalysis, and selective, spatially resolved doping of materials. Recently, a new type of FIB source has emerged, which uses ionization of laser cooled neutral atoms to produce the ion beam. The extremely cold temperatures attainable with laser cooling (in the range of 100 µK or below) result in a beam of ions with a very small transverse velocity distribution. This corresponds to a source with extremely high brightness that rivals or may even exceed the brightness of the industry standard Ga+ liquid metal ion source. In this review we discuss the context of ion beam technology in which these new ion sources can play a role, their principles of operation, and some examples of recent demonstrations. The field is relatively new, so only a few applications have been demonstrated, most notably low energy ion microscopy with Li ions. Nevertheless, a number of promising new approaches have been proposed and/or demonstrated, suggesting that a rapid evolution of this type of source is likely in the near future.

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Activating mutations in the receptor tyrosine kinase KIT, most notably KIT D816V, are commonly observed in patients with systemic mastocytosis. Thus, inhibition of KIT has been a major focus for treatment of this disorder. Here we investigated a novel approach to such inhibition. Utilizing rational drug design, we targeted the switch pocket (SP) of KIT, which regulates its catalytic conformation. Two SP inhibitors thus identified, DP-2976 and DP-4851, were examined for effects on neoplastic mast cell proliferation and mast cell activation. Autophosphorylation of both wild-type and, where also examined, KIT D816V activation was blocked by these compounds in transfected 293T cells, HMC 1.1 and 1.2 human mast cell lines, and in CD34(+)-derived human mast cells activated by stem cell factor (SCF). Both inhibitors induced apoptosis in the neoplastic mast cell lines and reduced survival of primary bone marrow mast cells from patients with mastocytosis. Moreover, the SP inhibitors more selectively blocked SCF potentiation of FcɛRI-mediated degranulation. Overall, SP inhibitors represent an innovative mechanism of KIT inhibition whose dual suppression of KIT D816V neoplastic mast cell proliferation and SCF-enhanced mast cell activation may provide significant therapeutic benefits.

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OBJECTIVE: The objective in this work is to investigate the feasibility of using a new imaging tool called vibro-acoustography (VA) as a means of permanent prostate brachytherapy (PPB) seed localization to facilitate post-implant dosimetry (PID). METHODS AND MATERIALS: Twelve OncoSeed (standard) and eleven EchoSeed (echogenic) dummy seeds were implanted in a human cadaver prostate. Seventeen seeds remained after radical retropubic prostatectomy. VA imaging was conducted on the prostate that was cast in a gel phantom and placed in a tank of degassed water. 2-D magnitude and phase VA image slices were obtained at different depths within the prostate showing location and orientation of the seeds. RESULTS: VA demonstrates that twelve of seventeen (71%) seeds implanted were visible in the VA image, and the remainder were obscured by intra-prostatic calcifications. Moreover, it is shown here that VA is capable of imaging and locating PPB seeds within the prostate independent of seed orientation, and the resulting images are speckle free. CONCLUSION: The results presented in this research show that VA allows seed detection within a human prostate regardless of their orientation, as well as imaging intra-prostatic calcifications.

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Mast cells have long been recognized for their role in the genesis of allergic inflammation; and more recently for their participation in innate and acquired immune responses. Mast cells reside within tissues including the skin and mucosal membranes, which interface with the external environment; as well as being found within vascularized tissues next to nerves, blood vessels and glandular structures. Mast cells have the capability of reacting both within minutes and over hours to specific stimuli, with local and systemic effects. Mast cells express the high affinity IgE receptor (FcepsilonRI) and upon aggregation of FcepsilonRI by allergen-specific IgE, mast cells release and generate biologically active preformed and newly synthesized mediators which are involved in many aspects of allergic inflammation. While mast cells have been well documented to be essential for acute allergic reactions, more recently the importance of mast cells in reacting through pattern recognition receptors in innate immune responses has become recognized. Moreover, as our molecular understanding of the mast cell has evolved, novel targets for modulation have been identified with promising therapeutic potential.

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Microbial forensics is a relatively new scientific discipline dedicated to analysing microbiological evidence from a crime for attribution purposes. It builds on traditional microbiology and epidemiology but within a legal framework. Important motives for forensic investigations include interdiction of criminals, prosecution of justice, and ideally, deterrence of others from committing similar acts. Forensic capabilities in animal health should focus on building capacity for detection and reporting of increases in infectious disease morbidity and mortality among animals that might reflect a covert release of a pathogen. Suspicion should be raised when epidemiological patterns are different from those expected for the animal population and the pathogen in question. Existing capacities for the detection and reporting of epidemic and even endemic diseases should be an international priority for the prevention of catastrophic losses in animal and potentially in human life. The veterinary community needs to be more aware of the legal requirements related to forensic investigations so that veterinarians will be prepared to handle evidence properly within their own fields.

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The horizontal transfer and effects on host fitness of a neutral gene cassette inserted into three different genomic loci of a plant-colonizing pseudomonad was assessed in a model ecosystem. The KX reporter cassette (kanamycin resistance, aph, and catechol 2, 3, dioxygenase, xylE) was introduced on the disarmed transposon mini-Tn5 into: (I) the chromosome of a spontaneous rifampicin resistant mutant Pseudomonas fluorescens SBW25R; (II) the chromosome of SBW25R in the presence of a naturally occurring lysogenic-phage (phage Phi101); and (III) a naturally occurring plasmid pQBR11 (330 kbp, tra+, Hgr) introduced into SBW25R. These bacteria were applied to Stellaria media (chickweed) plants as seed dressings [c. 5 x 104 colony-forming units (cfu)/seed] and the seedlings planted in 16 microcosm chambers containing model plant and animal communities. Gene transfer to pseudomonads in the phyllosphere and rhizosphere was found only in the plasmid treatment (III). Bacteria in the phage treatment (II) initially declined in density and free phage was detected, but populations partly recovered as the plants matured. Surprisingly, bacteria in the chromosome insertion treatment (I) consistently achieved higher population densities than the unmanipulated control and other treatments. Plasmids were acquired from indigenous bacterial populations in the control and chromosome insertion treatments. Plasmid acquisition, plasmid transfer from inocula and selection for plasmid carrying inocula coincided with plant maturation.

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In the past 100 years, to our knowledge there have been approximately 12 events involving the intentional introduction of microbiologic agents into livestock and animal populations worldwide, of which three were World War I events in the United States. To the best of the authors' knowledge, there has been no recent intentional introduction of microbiologic agents (viruses or bacteria) into livestock and animal populations in the United States. The criminal or terrorist use of chemicals against animals and agriculture products have been more common. With the political, economic, and military new world order, however, the United States must maintain a vigilant posture. The framework for this vigilance must be an intelligence system sensitive to the needs of agriculture and a first-class animal disease diagnostic surveillance and response system.

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When fluorescent pseudomonads are cultured on standard solid media under iron limiting conditions, they produce fluorescent, pigmented iron collating agents (siderophores). Siderophores can be readily identified by strong fluorescence seen under UV/blue light. The application of the eukaryotic green fluorescent protein (GFP) as a bacterial marker in microbial ecology is increasingly being used, particularly as it is a powerful method for non-destructive monitoring in situ. As gfp expressing bacteria have to be detected under UV/blue light, the fluorescence of siderophore-producing Pseudomonas spp. masks normal levels of GFP fluorescence when colonies are viewed on standard bacterial agar. Here, we describe a simple but effective way of identifying gfp-expressing Pseudomonas fluorescens using media supplemented with 0.45 mM FeSO(4).7H(2)O. This is of relevance for the screening of insertion libraries and in the application of GFP transposons as promoter probes.

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The causative agent of potato brown rot and bacterial wilt, Ralstonia solanacearum, results in serious world-wide economic losses, particularly in the tropics. In the last decade, however, the incidence of bacterial wilt in potatoes grown in Northern Europe has increased, presenting an interesting epidemiological puzzle. Its occurrence may be as a result of changes in agricultural practice or the emergence of a novel bacterial variety, better adapted to cooler conditions. To understand the distribution and genetic diversity of this phytopathogen, we have analysed a collection of 82 isolates from Europe and tropical regions. Both phenotypic [SDS-PAGE (sodium dodecyl sulphate polyacrylamide gel electrophoresis) profiling, FAME (fatty acid methyl esters) analysis, growth profiles and EPS (exopolysaccharide) production] and genotypic [16S rRNA RFLP (restriction fragment length polymorphism), ARDRA (amplified ribosomal DNA restriction analysis) and sequence analysis of 16S-23S rRNA ITS and flanking regions] methods were compared. Principal component analysis of FAME profiles clustered isolates into three groups and ARDRA of a 0.85 kb amplified fragment from the 16S-23S ITS region differentiated isolates into four groups. Using sequence analysis, specific primers were designed within the variable region 147-170 of the 23S rRNA. These primers, RsolT2 and RsolT3, respectively, differentiated isolates into two distinct clusters as described previously by Wullings and colleagues (Wullings et al., 1998). The European strains (Biovar 2, race 3) analysed in this study specifically hybridized with RsolT3, and showed considerable genetic homogeneity when compared with strains of other races from 'the rest of the world'. These data indicate the possible selection and proliferation of a 'European'-adapted variant.

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A disarmed Tn5 vector (pUT::Ptac-phzABCDEFG) was used to introduce a single copy of the genes responsible for phenazine-1-carboxylic acid (PCA) biosynthesis into the chromosome of a plant-growth-promoting rhizobacterium Pseudomonas fluorescens. The PCA gene cluster was modified for expression under a constitutive Ptac promoter and lacked the phzIR regulators. PCA-producing variants significantly improved the ability of the wild-type P. fluorescens to reduce damping-off disease of pea seedlings caused by Pythium ultimum, even under conditions of heavy soil infestation. Under conditions of oxygen limitation that are typical of the rhizosphere, PCA production per cell in vitro was greater than that recorded in fast-growing, nutrient-rich cultures. Similarly, when the in vitro nutrient supply was limited, P fluorescens::phz variants that produced the most PCA effectively competed against P. ultimum by suppressing mycelial development. Soil-based bioassays confirmed that the level of PCA biosynthesis correlated directly with the efficacy of biological control and the persistence of inocula in soil microcosms. They also showed that soil pretreatment with bacteria provides a suitable method for plant protection by reducing infection, effectively decontaminating the soil. These data demonstrate that the insertion of a single chromosomal copy of the genes for a novel antifungal compound, PCA, enhances the ecological fitness of a natural isolate already adapted to the rhizosphere and capable of suppressing fungal disease.

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OBJECTIVES: The delivery of thermotherapy, cryotherapy, and interstitial radiation with minimal morbidity is dependent on the preservation of the prostatic urethra. Our aim was to determine the distribution of the distance between the urethra and the nearest prostate cancer. METHODS: We determined the location of cancer in 350 prostate cancers treated by radical prostatectomy between 1991 and 1993. Each pathologic specimen was totally embedded, serially sectioned, and whole mounted. For each prostate, the radial distance from the urethra to the nearest cancer was determined (urethral-cancer distance). The urethra-cancer distance was correlated with the clinical, pathologic, and laboratory factors. Univariate and multivariate associations with progression-free survival were determined. RESULTS: The mean follow-up was 6.1 years. Ninety-three patients had biochemical, local, or systemic cancer recurrence. The mean +/- SD distance from the urethra to the nearest cancer was 3 +/- 3 mm (range 0 to 18). In 58 patients (17%), the cancer touched the urethra. A decreasing urethra-cancer distance was associated with increasing rates of cancer recurrence (P = 0.009). The urethra-cancer distance correlated with each of the following preoperative factors: preoperative prostate-specific antigen (r = -0. 22, P <0.001), Gleason score in biopsy specimen (r = -0.13, P = 0.02), and percentage of Gleason score 4 or 5 in the biopsy specimen (r = -0.17, P = 0.008). CONCLUSIONS: The distance between the urethra and the nearest cancer was associated with prostate cancer outcome. Many patients have cancer close to the urethra. This finding may have implications for nonsurgical ablative therapies for prostate cancer.

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New voluntary individual savings accounts have been proposed by some as a part of, or in addition to, Social Security. The success of these proposals would depend greatly on how many workers participate. This paper compares participation rates in three existing voluntary individual account-type plans--Individual Retirement Accounts (IRAs), 401(k)s, and the federal Thrift Savings Plan (TSP)--to clarify expectations about who might participate in a voluntary individual account system. It finds that participants in IRAs, 401(k)s, and the TSP tend to be disproportionately male, higher earners, older, full-time workers, and either white or nonblack minorities compared with the population at large. Differences in earnings explain much of the difference between participation rates of men and women, however, but less of the difference between participation rates of workers of different races. Whether participation in a new system of voluntary individual accounts would resemble participation in IRAs, 401(k)s, or the TSP would depend on a number of factors. For instance, the population covered by 401(k)s and the TSP is much smaller than that covered by Social Security. Average earnings are also higher among 401(k) and TSP participants than for workers covered by Social Security, which, based on these findings, suggests that participation rates could be lower in a universal system. Participation would also depend on many other factors, however, such as the extent of matching contributions or other financial incentives, the investment options available, and the amount of education provided to potential participants.

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A rapid immunological method for trapping and selection of functionally regulated prokaryotic promoters is described. The method is based on application of a novel mini-Tn5 derived promoter probe (pUTTKZY-promoterless lacZY as a reporter and kanamycin resistance) to mutagenise a plant growth promoting fluorescent pseudomonad, Pseudomonas fluorescens 54/96. The transposon allows selection of operon fusion mutants (lacZY(+)) directly on media containing lactose as a sole carbon source as well as selection for kanamycin and lacZ (beta-galactosidase) expression on X-gal indicator media. We have extended the technique to target the surface expression of the induced lactose permease gene (lacY) from mutagenised libraries and the immuno-capture of bacteria with magnetic beads and anti-LacY monospecifc antisera. The benefits of the lacZY reporter are that a library can be rapidly generated and screened in vitro to isolate non-expressed mutants for further in situ screening. Here we demonstrate the development and utility of the technique and its potential as a differential display method for the isolation of promoters that direct regulated gene expression in the phytosphere, or under other imposed conditions.

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PURPOSE: Successful treatment with ultrasound-guided transperineal interstitial permanent prostate brachytherapy (TIPPB) relies on effective radiation coverage of intraprostatic and clinically occult extraprostatic cancer. This study examines prostatectomy findings as they relate to treatment of extraprostatic extension (EPE) of cancer and TIPPB techniques and dosimetry. MATERIALS AND METHODS: A total of 313 prostatectomy specimens from patients with clinical tumor classification T1-T2b adenocarcinomas, serum prostate-specific antigen <20 ng/mL, and Gleason score <8 were whole mounted and evaluated for intraprostatic cancer volume and extraprostatic radial distance, area of perforation, and cancer density. From these data, extraprostatic cancer volume is calculated and used to estimate extraprostatic tumor control probabilities using the linear quadratic radiobiological model and Poisson statistics. TIPPB dose-gradient characteristics at the prostate periphery are examined. RESULTS: Intraprostatic cancer volume ranges from 0 to 38 cc, whereas extraprostatic cancer volume ranges from 0 to 4.6 cc (mean 0.06 cc). The radial distance of EPE ranges from 0 to 4.4 mm (mean 0.18 mm). The ratio of extraprostatic to intraprostatic cancer volume ranges from 0% to 18% (mean 0.4%). CONCLUSIONS: Only small amounts of clinically occult extraprostatic cancer were identified in the majority of specimens with EPE. Tumor control probability calculations suggest that this volume of cancer may be treated effectively with TIPPB. Treatment of this cancer possibly is achieved with an intraprostatic implant, but treatment of all cancers identified in this study suggests that some extraprostatic seed placement is desirable.

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Based on cross-sectional data, we recently reported that, in contrast to the prevailing view, the rate of decline in maximal oxygen consumption (VO(2 max)) with age is greater in physically active compared with sedentary healthy women. We tested this hypothesis in men using a meta-analytic study of VO(2 max) values in the published literature. A total of 242 studies (538 subject groups and 13,828 subjects) met the inclusion criteria and were arbitrarily separated into sedentary (214 groups, 6,231 subjects), active (159 groups, 5,621 subjects), and endurance-trained (165 groups, 1,976 subjects) populations. Body fat percent increased with age in sedentary and active men (P < 0.001), whereas no change was observed in endurance-trained men. VO(2 max) was inversely and strongly related to age within each population (r = -0.80 to -0.88, all P < 0. 001) and was highest in endurance-trained and lowest in sedentary populations at any age. Absolute rates of decline in VO(2 max) with age were not different (P > 0.05) in sedentary (-4.0 ml. kg(-1). min(-1). decade(-1)), active (-4.0), and endurance-trained (-4.6) populations. Similarly, there were no group differences (P > 0.05) in the relative (%) rates of decline in VO(2 max) with advancing age (-8.7, -7.3, and -6.8%/decade, respectively). Maximal heart rate was inversely related to age within each population (r = -0.88 to -0.93, all P < 0.001), but the rate of age-related reduction was not different among the populations. There was a significant decline in running mileage and speed with advancing age in the endurance-trained men. The present cross-sectional meta-analytic findings do not support the hypothesis that the rate of decline in VO(2 max) with age is related to habitual aerobic exercise status in men.

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