Association between a genetic index for digital dermatitis resistance and the presence of digital dermatitis, heel horn erosion, and interdigital hyperplasia in Holstein cows.

Digital dermatitis (DD) is a polybacterial disease endemic to most UK dairy farms. It poses a major financial and welfare threat and is characterized by high incidence and recurrence rates. We aimed to investigate the association between the UK EBV for resistance to digital dermatitis, the digital dermatitis index (DDI), and the frequency of DD, heel horn erosion (HHE), and interdigital hyperplasia (IH) in a population of Holstein dairy cows. We enrolled and genotyped 2,352 cows from 4 farms in a prospective cohort study. Foot lesion records were recorded by veterinary surgeons for each animal at 4 time points during a production cycle, starting at approximately 2 mo before calving and ending in late lactation. Importantly, these records were not used in the calculation of the DDI. Lesion records were matched to the animal's own DDI (n = 2,101) and their sire's DDI (n = 1,812). Digital dermatitis index values in our study population ranged from -1.41 to +1.2 and were transformed to represent distance from the mean expressed in SD. The relationship between the DDI and the presence of DD was investigated using a logistic regression model, with farm, parity, and a farm-parity interaction fitted as covariates. A multivariable logistic regression model was fitted to evaluate the relationship between HHE and DDI with farm fitted as a covariate. Finally, a univariable logistic regression model with DDI as explanatory variable was used to investigate the relationship between IH and DDI. The odds ratio of an animal being affected by DD was 0.69 for 1 SD increase in the animal's DDI (95% CI = 0.63-0.76). The odds of HHE and IH were 0.69 (95% CI = 0.62-0.76) and 0.58 (95% CI = 0.49-0.68) respectively for 1 SD increase in DDI. The adjusted probability of DD was 32% (95% CI = 27-36%) for cows with mean DDI value of 0, while it was 24% (95% CI = 20-29%) in cows with a DDI value of +1. Sire DDI breeding values were standardized in the same way and then binned into terciles creating an ordinal variable representing bulls of high, medium, and low genetic merit for DD resistance. The daughters of low genetic merit bulls were at 2.05 (95% CI = 1.60-2.64), 1.96 (95% CI = 1.53-2.50), and 2.85 (95% CI = 1.64-5.16) times greater odds of being affected by DD, HHE, and IH, respectively, compared with the daughters of high genetic merit bulls. The results of this study highlight the potential of digital dermatitis genetic indexes to aid herd management of DD, and suggest that breeding for resistance to DD, alongside environmental and management control practices, could reduce the prevalence of the disease.

Development and validation of a fully automated 2-dimensional imaging system generating body condition scores for dairy cows using machine learning.

Monitoring body condition score (BCS) is a useful management tool to estimate the energy reserves of an individual cow or a group of cows. The aim of this study was to develop and evaluate the performance of a fully automated 2-dimensional imaging system using a machine learning algorithm to generate real-time BCS for dairy cows. Two separate datasets were used for training and testing. The training dataset included 34,150 manual BCS (MAN_BCS) assigned by 5 experienced veterinarians during 35 visits at 7 dairy farms. Ordinal regression methods and deep learning architecture were used when developing the algorithm. Subsequently, the testing dataset was used to evaluate the developed BCS prediction algorithm on 4 of the participating farms. An experienced human assessor (HA1) visited these farms and performed 8 whole-milking-herd BCS sessions. Each farm was visited twice, allowing for 30 d (±2 d) to pass between visits. The MAN_BCS assigned by HA1 were considered the ground truth data. At the end of the validation study, MAN_BCS were merged with the stored automated BCS (AI_BCS), resulting in a testing dataset of 9,657 single BCS. A total of 3,817 cows in the testing dataset were scored twice 30 d (±2 d) apart, and the change in their BCS (ΔBCS) was calculated. A subset of cows at one farm were scored twice on consecutive days to evaluate the within-observer agreement of both the human assessor and the system. The manual BCS of 2 more assessors (HA2 and HA3) were used to assess the interobserver agreement between humans. Finally, we also collected ultrasound measurements of backfat thickness (BFT) from 111 randomly selected cows with available MAN_BCS and AI_BCS. Using the testing dataset, intra- and interobserver agreement for single BCS and ΔBCS were estimated by calculating the simple percentage agreement (PA) at 3 error levels and the weighted kappa (κw) for the exact agreement. A Bland-Altman plot was constructed to visualize the systematic and proportional bias. The association between MAN_BCS and AI_BCS and the BFT was assessed with Passing-Bablok regressions. The system had an almost perfect repeatability with a κw of 0.99. The agreement between MAN_BCS and AI_BCS was substantial, with an overall κw of 0.69. The overall PA at the exact, ± 0.25-unit, and ± 0.50-unit BCS error range between MAN_BCS and AI_BCS was 44.4%, 84.6%, and 94.8%, respectively, and greater than the PA obtained between HA1 and HA3. The Bland-Altman plot revealed a minimal systematic bias of -0.09 with a proportional bias at the extreme scores. Furthermore, despite the low κw of 0.20, the overall PA at the exact and ± 0.25-unit of BCS error range between MAN_BCS and AI_BCS regarding the ΔBCS was 45.7 and 88.2%, respectively. A strong linear relationship was observed between BFT and AI_BCS (ρ = 0.75), although weaker than that between BFT and MAN_BCS (ρ = 0.91). The system was able to predict single BCS and ΔBCS with satisfactory accuracy, comparable to that obtained between trained human scorers.

Specific pathway abundances in the neonatal calf faecal microbiome are associated with susceptibility to Cryptosporidium parvum infection: a metagenomic analysis.

BACKGROUND: Cryptosporidium parvum is the main cause of calf scour worldwide. With limited therapeutic options and research compared to other Apicomplexa, it is important to understand the parasites' biology and interactions with the host and microbiome in order to develop novel strategies against this infection. The age-dependent nature of symptomatic cryptosporidiosis suggests a link to the undeveloped immune response, the immature intestinal epithelium, and its associated microbiota. This led us to hypothesise that specific features of the early life microbiome could predict calf susceptibility to C. parvum infection. RESULTS: In this study, a single faecal swab sample was collected from each calf within the first week of life in a cohort of 346 animals. All 346 calves were subsequently monitored for clinical signs of cryptosporidiosis, and calves that developed diarrhoea were tested for Rotavirus, Coronavirus, E. coli F5 (K99) and C. parvum by lateral flow test (LFT). A retrospective case-control approach was taken whereby a subset of healthy calves (Control group; n = 33) and calves that went on to develop clinical signs of infectious diarrhoea and test positive for C. parvum infection via LFT (Cryptosporidium-positive group; n = 32) were selected from this cohort, five of which were excluded due to low DNA quality. A metagenomic analysis was conducted on the faecal microbiomes of the control group (n = 30) and the Cryptosporidium-positive group (n = 30) prior to infection, to determine features predictive of cryptosporidiosis. Taxonomic analysis showed no significant differences in alpha diversity, beta diversity, and taxa relative abundance between controls and Cryptosporidium-positive groups. Analysis of functional potential showed pathways related to isoprenoid precursor, haem and purine biosynthesis were significantly higher in abundance in calves that later tested positive for C. parvum (q ≤ 0.25). These pathways are either absent or streamlined in the C. parvum parasites. Though the de novo production of isoprenoid precursors, haem and purines are absent, C. parvum has been shown to encode enzymes that catalyse the downstream reactions of these pathway metabolites, indicating that C. parvum may scavenge those products from an external source. CONCLUSIONS: The host has previously been put forward as the source of essential metabolites, but our study suggests that C. parvum may also be able to harness specific metabolic pathways of the microbiota in order to survive and replicate. This finding is important as components of these microbial pathways could be exploited as potential therapeutic targets for the prevention or mitigation of cryptosporidiosis in bovine neonates.

The bovine foot skin microbiota is associated with host genotype and the development of infectious digital dermatitis lesions.

BACKGROUND: Bovine Digital Dermatitis (BDD) is a prevalent infectious disease, causing painful foot skin lesions and lameness in cattle. We describe herein the bovine foot skin microbiota and its associations with BDD using 16S rRNA gene amplicon and shotgun metagenomic sequencing on samples from 259 dairy cows from three UK dairy farms. RESULTS: We show evidence of dysbiosis, and differences in taxonomy and functional profiles in the bovine foot skin microbiome of clinically healthy animals that subsequently develop BDD lesions, compared to those that do not. Our results suggest that taxonomical and functional differences together with alterations in ecological interactions between bacteria in the normal foot skin microbiome may predispose an animal to develop BDD lesions. Using genome-wide association and regional heritability mapping approaches, we provide first evidence for interactions between host genotype and certain members of the foot skin microbiota. We show the existence of significant genetic variation in the relative abundance of Treponema spp. and Peptoclostridium spp. and identify regions in the bovine genome that explain a significant proportion of this variation. CONCLUSIONS: Collectively this work shows early changes in taxonomic and functional profiles of the bovine foot-skin microbiota in clinically healthy animals which are associated with subsequent development of BDD and could be relevant to prevention of disease. The description of host genetic control of members of the foot skin microbiota, combined with the association of the latter with BDD development offer new insights into a complex relationship that can be exploited in selective breeding programmes. Video Abstract.

Latent tetany associated with the hypokalaemia of Conn's syndrome.

We describe the case of an asymptomatic patient with primary hyperaldosteronism, who was diagnosed fortuitously following the demonstration of a positive Trousseau's sign during routine blood pressure assessment. Further investigations revealed that the carpal spasm was due solely to the associated profound hypokalaemia.

Pre-hospital cardiac arrest associated with coronary artery spasm.

A 37-yr-old woman with an 8-month history of chest pain, unrelated to exercise, was successfully resuscitated from out-of-hospital cardiac arrest due to ventricular fibrillation. Cardiac catheterisation revealed minor coronary artery disease. Ergometrine injection was associated with complete occlusion of the left anterior descending coronary associated with identical chest pain and pronounced ST-segment changes.

Half-life of digoxin in myocardium after stopping maintenance treatment.

The rate of decline of digoxin level in myocardium was estimated from operative samples of atrial and ventricular tissue from 40 patients undergoing cardiac surgery 1-20 days after maintenance digoxin treatment was stopped. Linear regression of myocardial log concentration-time curves for the group as a whole gave half-lives of 2.9 and 3.1 days in ventricular and atrial myocardium, respectively. Serum concentrations of digoxin were measured twice in each patient in this study: once while receiving treatment and once at the time of operation. Analysis of the 22 pairs of serum samples in which the second sample contained measurable levels of digoxin gave an estimated half-life of 2.3 days. The serum half-life was shorter than either the ventricular or the atrial myocardial half-life when data were analysed by unpaired statistics. Considering data only from those patients in whom the serum half-life was measured, to allow comparison by paired statistics, estimated ventricular and atrial half-lives were 1.5 and 1.3 days, respectively, which are significantly less than the respective serum half-lives of 2.3 and 2.1 days. Relatively slow clearance of digoxin from myocardium received further, anecdotal support from its demonstration in one patient 20 days after treatment was stopped.

Haemodynamics and plasma concentrations following sublingual GTN and intravenous, or inhaled, isosorbide dinitrate.

We measured plasma nitrate levels and haemodynamics following sublingual glyceryl trinitrate (GTN) (0.5 mg), or isosorbide dinitrate (ISDN) administered intravenously (0.5 mg) or by inhalation (1.25 mg) in 23 patients undergoing cardiac catheterisation for investigation of chest pain. Peak levels were detected at 90 s and 5 min following intravenous and inhaled ISDN respectively and at 3 min following sublingual GTN. Intravenous and inhaled ISDN produced similar plasma levels at 30 s and both were significantly greater than following sublingual GTN. Plasma levels were maintained for longer following inhaled ISDN than intravenous ISDN or sublingual GTN. Haemodynamic responses were qualitatively similar following each treatment; reduction in pulmonary vascular resistance and pressure and left ventricular end diastolic pressure occurred in each group. Heart rate, cardiac output and LV dP/dt.P-1 remained unchanged. Maximal haemodynamic responses were greater following ISDN than GTN, with little difference between the two preparations of ISDN. Haemodynamic responses were more sustained following inhaled ISDN than following sublingual GTN or intravenous ISDN, the latter two being similar in this respect. These findings suggest that inhaled ISDN may provide more rapid and sustained relief from angina than sublingual GTN.

Effect of timolol on clinical features and echocardiographic assessment of left ventricular function in hyperthyroidism.

The effect of timolol, a beta-adrenoceptor blocking drug on the clinical status, thyroid status and left ventricular function as measured by serial M-mode echocardiographic recordings was assessed in a double-blind randomised study in 18 hyperthyroid patients. A significant clinical improvement was documented after 2 weeks of timolol treatment compared with placebo. There was no evidence that timolol impaired peripheral monodeiodination of thyroxine (T4). There were significant increases in left ventricular fractional shortening (Fr. Sh.) and velocity of circumferential shortening (Vcf) as well as a significant decrease in the left ventricular systolic internal dimension (LVIDs) (all P less than 0.01) in the untreated thyrotoxic patients compared with a normal euthyroid control group. After timolol treatment (2/52) there were significant increases in LVIDs and LVIDd and a significant decrease in Vcf (all P less than 0.05). No further changes occurred after a further 2/52 treatment with carbimazole. The cardiac data suggest that both an augmented sympathetic drive and a direct effect of thyroid hormone on myocardial contractility are mediators of the haemodynamic changes in hyperthyroidism.

Clinical and echocardiographic assessment of the Medtronic-Hall valve: experience with 370 implanted valves.

During a 34-month period, 370 Medtronic-Hall valves were implanted into 310 patients. Twenty-four percent of patients had additional operative procedures. Hospital mortality was 7% and late mortality to date is 3%. No deaths were due to thromboembolic complications or mechanical failure of the valve. The overall embolic rate was 2.5 per 100 patient years. For mitral valve replacement, the embolic rate was 3.5 per 100 patient years. Patients with isolated mitral valve replacement were subjected to detailed clinical and echocardiographic assessment. Eighty-nine percent of patients with 29 or 31 mm mitral prostheses improved one NYHA class or more and 33% improved 2 classes or more. For the 25 mm mitral prostheses, the figures were 91% and 38% respectively. The peak rate of increase of left ventricular dimension in diastole (dD/dt) was measured echocardiographically in subjects with normal native mitral valves and in patients with 29 or 31 mm Medtronic-Hall valves, Björk-Shiley valves and Starr-Edwards valves. Peak dD/dt in the native valves was 15.8 +/- 0.8, in Medtronic-Hall valves 13.9 +/- 0.8, in Björk-Shiley 11.6 +/- 1.0 and in Starr-Edwards 9.5 +/- 0.6. The Björk-Shiley and Starr-Edwards valves differed significantly from normal (p less than 0.05 and less than 0.001 respectively) but there was no significant difference between the Medtronic-Hall valves and the native ones. We conclude that the Medtronic Hall valve is a safe and hemodynamically effective valve in the mitral position.

M-mode echocardiographic features of severe aortic valve endocarditis.

We describe and discuss the M-mode echocardiographic features in 10 patients with infective endocarditis of the aortic valve requiring surgery. Operative findings and aortic valve histology were obtained in each case. Vegetations were visualized in six out of seven patients (86%) with proven vegetations while pre-existing aortic valve disease masked their echocardiographic recognition in one patient. Diastolic echoes indistinguishable from vegetations were recorded from the ragged edge of a perforated aortic cusp in one patient who at operation had no demonstrable vegetations. Left ventricular outflow tract (LVOT) echoes were seen in five patients. Non-vibrating LVOT echoes were identified as vegetations while rapidly vibrating LVOT echoes were recorded from a flail aortic cusp. Premature mitral valve closure (PMVC) was seen in five out of seven patients (70%) with a short (less than or equal to four month) history of severe aortic regurgitation. Subannular aneurysms were detected in three out of five patients (60%) with this complication. Increased septal and left ventricular posterior wall motion suggestive of severe aortic regurgitation was seen in each case. The detection of a flail aortic valve leaflet, PMVC and subannular aneurysms indicates the need for surgery. The demonstration of vegetations defines a further subgroup of patients who should be managed in a centre with facilities for cardiac surgery. Echocardiography obviated the need for pre-operative cardiac catheterization in nine out of 10 patients (90%).

Maintenance of the inotropic effect of digoxin on long-term treatment.

M-mode echocardiograms and systolic time intervals were recorded before and six weeks after stopping digoxin in 11 patients in sinus rhythm to see whether the inotropic effect of digoxin was maintained with long-term treatment. Significant changes indicating a reduction in inotropic state on stopping digoxin were observed in the group. Clinical deterioration occurred in only one patient, associated with evidence of initially impaired cardiac function rather than an atypical response to digoxin. This study provides evidence that chronic digoxin treatment does continue to exert a positive inotropic effect.

Echocardiographic detection of subvalvar aortic root aneurysm extending to mitral valve annulus as complication of aortic valve endocarditis.

Acute aortic regurgitation as a consequence of infective endocarditis developed in a young man after peritonitis. A large subvalvar aortic root aneurysm extending to the mitral valve annulus together with features of severe acute aortic regurgitation were shown by M-mode echocardiography. The echocardiographic findings were confirmed at operation when obliteration of the aneurysmal space and aortic valve replacement were performed. Postoperative echocardiography confirmed obliteration of the aneurysmal space.

Assessment of chronic aortic valve disease in adults.

Chronic aortic valve disease is often tolerated for a long period of time with little in the way of symptoms, but once symptoms develop, the downhill course is often rapid. Medical therapy may alleviate symptoms of congestive heart failure and angina, but does not alter the natural history of the disease. The recent advances of cardiac surgery have, however, considerably improved the prognosis of most patients. Some patients with aortic regurgitation, though, will develop progressive congestive heart failure despite aortic valve replacement. Others with severe aortic stenosis will die suddenly while awaiting surgery as will a small number who previously had been asymptomatic. The information that comes from cardiac catheterization as well as the non-invasive investigation of cardiological disease, greatly enhanced by the introduction of the echocardiogram, has provided the physician with a better understanding of the particular problems in question and, therefore, the potential to solve them. This article aims to review the means by which high-risk groups can be identified, in order that their outlook may be improved especially with respect to the timing of surgical intervention.