Apixaban in a porcine model of mechanical valve thrombosis in pulmonary position-a pilot study.

OBJECTIVES: The newest mechanical valves have low thrombogenicity, making them candidates for anticoagulation with a direct oral anticoagulant. While these drugs hold great promise to replace warfarin, clinical trials have been disappointing so far. We aimed to evaluate apixaban in a porcine model of mechanical valve thrombosis with On-X® (CryoLife) aortic valves implanted in pulmonary position. METHODS: On-X® valves were implanted in pulmonary valve position in 9 Yucatan pigs. Animals received prophylactic enoxaparin 40 mg for 1 week. Pigs in the low-dose group received 5 mg apixaban twice daily for 10 weeks. The intermediary-dose group received 5 mg twice daily for 6 weeks and then 10 mg twice daily afterwards. The high-dose group received 15 mg twice daily for 10 weeks. After sacrifice, valves were macroscopically evaluated and thrombus weight was documented. RESULTS: The median weight of the 9 animals was 64.3 kg, range 52.5-70.9. In the low-dose group (2 animals), both valves showed manifest, chronic thrombosis with blocked hinges. In the intermediary-dose group, a normal functioning valve without thrombosis was seen in 2/4 animals. In the high-dose group (3 pigs), there was no valve thrombosis. No bleeding events occurred. In all animals, apixaban plasma levels were low compared to clinical target levels. CONCLUSIONS: The pulmonary position seems to be an aggressive model for mechanical valve thrombosis in pigs. Apixaban has the potential to prevent valve thrombosis, even in these thrombogenic conditions. Detailed pharmacokinetic studies are needed to determine the ideal apixaban dosage for future experiments and to enable extrapolation to the clinical situation.

Distinct Campylobacter fetus lineages adapted as livestock pathogens and human pathobionts in the intestinal microbiota.

Campylobacter fetus is a venereal pathogen of cattle and sheep, and an opportunistic human pathogen. It is often assumed that C. fetus infection occurs in humans as a zoonosis through food chain transmission. Here we show that mammalian C. fetus consists of distinct evolutionary lineages, primarily associated with either human or bovine hosts. We use whole-genome phylogenetics on 182 strains from 17 countries to provide evidence that C. fetus may have originated in humans around 10,500 years ago and may have "jumped" into cattle during the livestock domestication period. We detect C. fetus genomes in 8% of healthy human fecal metagenomes, where the human-associated lineages are the dominant type (78%). Thus, our work suggests that C. fetus is an unappreciated human intestinal pathobiont likely spread by human to human transmission. This genome-based evolutionary framework will facilitate C. fetus epidemiology research and the development of improved molecular diagnostics and prevention schemes for this neglected pathogen.

The value of trans-scrotal ultrasonography at bull breeding soundness evaluation (BBSE): The relationship between testicular parenchymal pixel intensity and semen quality.

Bull breeding soundness evaluation (BBSE) is commonly undertaken to identify bulls that are potentially unfit for use as breeding sires. Various studies worldwide have found that approximately 20% of the bulls fail their routine prebreeding BBSE and are therefore considered subfertile. Multiple articles describe the use of testicular ultrasound as a noninvasive aid in the identification of specific testicular and epididymal lesions. Two previous studies have hypothesized a correlation between ultrasonographic testicular parenchymal pixel intensity (PI) and semen quality; however to date, no published studies have specifically examined this link. The aim of this study, therefore, was to assess the relationship between testicular parenchymal PI (measured using trans-scrotal ultrasonography) and semen quality (measured at BBSE), and the usefulness of testicular ultrasonography as an aid in predicting future fertility in bulls, in particular those that are deemed subfertile at the first examination. A total of 162 bulls from 35 farms in the South East of Scotland were submitted to routine BBSE and testicular ultrasonography between March and May 2014, and March and May 2015. Thirty-three animals failed their initial examination (BBSE1) due to poor semen quality, and were re-examined (BBSE2) 6 to 8 weeks later. Computer-aided image analysis and gross visual lesion scoring were performed on all ultrasonograms, and results were compared to semen quality at BBSE1 and BBSE2. The PI measurements were practical and repeatable in a field setting, and although the results of this study did not highlight any biological correlation between semen quality at BBSE1 or BBSE2 and testicular PI, it did identify that gross visual lesion scoring of testicular images is comparable to computer analysis of PI (P < 0.001) in identifying animals suffering from gross testicular fibrosis.

Diagnosis and management of venereal campylobacteriosis in beef cattle.

BACKGROUND: Bovine venereal campylobacteriosis is caused by Campylobacter fetus subsp. venerealis and its glycerine-tolerant variant Campylobacter fetus subsp. venerealis biovars intermedius. The disease can be economically important when present in cattle herds, causing poor reproductive performance, embryo mortality and abortion. Sensitive and specific diagnostic tests are required in the diagnosis of infection and to inform and monitor disease control. Current tests include bacterial culture and fluorescent antibody testing of preputial sheath washings and an enzyme-linked immunosorbent assay and an agglutination test on vaginal mucus, although the predictive values of these tests can be inadequate in field investigations. Artificial insemination is often considered as a simple control method for bovine venereal campylobacteriosis, but is impractical for many beef suckler herds where breeding takes place at pasture. Commercial vaccines are unavailable in the UK, while the efficacy of autogenous vaccines using a bacterial isolate from infected animals on a specific farm is at best unproven. Hence, for some infected herds, the development of an alternative control strategy based on segregation of potentially infected and uninfected animals in combination with culling or treatment would be desirable. This approach requires meticulous records and herd health management. CASE PRESENTATION: In this paper we highlight difficulties in diagnosing bovine venereal campylobacteriosis and demonstrate the benefits of good record keeping when investigating poor reproductive performance in a beef suckler herd and establishing a herd-specific approach to bio-containment of the infectious cause. CONCLUSIONS: Bovine venereal campylobacteriosis is an economically important disease that should be considered in investigations of suckler herd subfertility problems. Control of the disease based on segregation of potentially infected and uninfected animals in combination with extensive culling can be achieved without the use of artificial insemination or vaccination, but requires meticulous records and strict adherence to herd biosecurity practices.