Deleterious AGXT Missense Variant Associated with Type 1 Primary Hyperoxaluria (PH1) in Zwartbles Sheep.

Severe oxalate nephropathy has been previously reported in sheep and is mostly associated with excessive oxalate in the diet. However, a rare native Dutch breed (Zwartbles) seems to be predisposed to an inherited juvenile form of primary hyperoxaluria and no causative genetic variant has been described so far. This study aims to characterize the phenotype and genetic etiology of the inherited metabolic disease observed in several purebred Zwartbles sheep. Affected animals present with a wide range of clinical signs including condition loss, inappetence, malaise, and, occasionally, respiratory signs, as well as an apparent sudden unexpected death. Histopathology revealed widespread oxalate crystal deposition in kidneys of the cases. Whole-genome sequencing of two affected sheep identified a missense variant in the ovine AGXT gene (c.584G>A; p.Cys195Tyr). Variants in AGXT are known to cause type I primary hyperoxaluria in dogs and humans. Herein, we present evidence that the observed clinicopathological phenotype can be described as a form of ovine type I primary hyperoxaluria. This disorder is explained by a breed-specific recessively inherited pathogenic AGXT variant. Genetic testing enables selection against this fatal disorder in Zwartbles sheep as well as more precise diagnosis in animals with similar clinical phenotype. Our results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 001672-9940).

Perinatal mortality in 23 beef herds in Orkney: incidence, risk factors and aetiology.

BACKGROUND: Perinatal mortality in beef calves impacts on profitability and animal welfare, but the incidence and causes in UK herds are not well known. METHODS: Data from 11 herds were analysed to establish the risk factors for and incidence of perinatal mortality (full-term calves born dead or died within 48 hours). To establish cause of death, 23 herds in total submitted dead calves for postmortem examination (nine herds submitted all calves, 14 herds submitted calves on an ad hoc basis) and the results were reviewed by a panel. RESULTS: The incidence of perinatal mortality for all 1059 calvings was 5.1 per cent (range 1.6-12.4 per cent across herds; median 4 per cent). The incidence of stillbirth and neonatal mortality was 3.9 per cent (range 0-10.1 per cent) and 1.2 per cent (range 0-2.6 per cent), respectively. Sex of the calf, plurality and level of calving assistance were associated with significantly greater risk of perinatal loss. Parturition-related deaths (n=20), intrauterine infections (n=13), congenital malformations (n=6) and postpartum infections (n=6) were among the diagnosis recorded from 54 calves investigated. Parturition-related deaths and congenital malformations were recorded more commonly from herds submitting all losses than from those submitting on an ad hoc basis. CONCLUSION: Variation in perinatal incidence across herds exists and many fail to reach the 2 per cent target. Some significant risk factors and common causes of death identified have the potential to decrease perinatal mortality rates through improved herd management.

Auto-titrating continuous positive airway pressure treatment for obstructive sleep apnoea after acute quadriplegia (COSAQ): study protocol for a randomized controlled trial.

BACKGROUND: Quadriplegia is a severe, catastrophic injury that predominantly affects people early in life, resulting in lifelong physical disability. Obstructive sleep apnoea is a direct consequence of quadriplegia and is associated with neurocognitive deficits, sleepiness and reduced quality of life. The usual treatment for sleep apnoea is nasal continuous positive airway pressure (CPAP); however, this is poorly tolerated in quadriplegia. To encourage patients to use this therapy, we have to demonstrate that the benefits outweigh the inconvenience. We therefore propose a prospective, multinational randomized controlled trial of three months of CPAP for obstructive sleep apnoea after acute quadriplegia. METHODS/DESIGN: Specialist spinal cord injury centres across Australia, New Zealand, the UK and Canada will recruit medically stable individuals who have sustained a (new) traumatic quadriplegia (complete or incomplete second cervical to first thoracic level lesions). Participants will be screened for obstructive sleep apnoea using full, portable sleep studies. Those with an apnoea hypopnoea index greater than 10 per hour will proceed to an initial three-night trial of CPAP. Those who can tolerate CPAP for at least 4 hours on at least one night of the initial trial will be randomized to either usual care or a 3-month period of auto-titrating CPAP. The primary hypothesis is that nocturnal CPAP will improve neuropsychological functioning more than usual care alone. The secondary hypothesis is that the magnitude of improvement of neuropsychological function will be predicted by the severity of baseline sleepiness measures, sleep fragmentation and sleep apnoea. Neuropsychological tests and full polysomnography will be performed at baseline and 3 months with interim measures of sleepiness and symptoms of autonomic dysfunction measured weekly. Spirometry will be performed monthly. Neuropsychological tests will be administered by blinded assessors. Recruitment commenced in July 2009. DISCUSSION: The results of this trial will demonstrate the effect of nocturnal CPAP treatment of obstructive sleep apnoea in acute quadriplegia. If CPAP can improve neurocognitive function after injury, it is likely that rehabilitation and subsequent community participation will be substantially improved for this group of predominantly young and severely physically disabled people. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12605000799651.

Bioexclusion of diseases from dairy and beef farms: risks of introducing infectious agents and risk reduction strategies.

Infectious disease represents a major threat to the productivity and welfare of cattle herds throughout the world. The introduction of infectious agents into dairy and beef farms may be through direct transmission (purchased cattle, reintroduced resident cattle and contact with contiguous cattle) or indirect transmission (fomites, visitors, other species, and biological materials) and this article reviews the evidence supporting these transmission routes. In the absence of eradication programmes for many endemic infectious diseases, bioexclusion is the key management process for risk reduction. Various ameliorative bioexclusion strategies have been recommended and the evidence supporting these protocols is considered.