Genetic improvement of canine hip dysplasia through sire selection across countries.

Breeding against canine hip dysplasia (HD) may benefit from the importation of foreign sires. When foreign sires are evaluated on a different HD scale, this may diminish the efficacy. Using stochastic simulations, we evaluated genetic change and inbreeding levels for different scenarios of importing sires with high genetic merit for HD. Population size and genetic parameters (e.g. heritability, accuracy of selection, genetic correlation) were based on actual data for HD in Golden retrievers and Labrador retrievers in the UK and Sweden. For countries with different HD scales and an estimated breeding value (EBV) evaluation in place, the importation was useful if imported sires had EBV rankings in the top 50% and if genetic correlations between EBV systems were above 0.85. When importing sires with EBV rankings in the top 10%, moderate accuracies of EBVs (>0.40) and moderately strong genetic correlations (>0.70) were needed. Selection against HD without the importation of sires may increase inbreeding levels, while the importation of sires can decrease inbreeding levels. For national genetic evaluation and selection programmes, importing sires with high genetic merit can be an effective breeding strategy, but care is needed to estimate reliable EBVs.

Fetal bovine serum induces sustained, but reversible, epithelial-mesenchymal transition in the BEAS-2B cell line.

BEAS-2B is a non-malignant, immortalized human cell line that has been used extensively as a model of lung epithelium. Despite ATCC recommendations to culture BEAS-2B in defined, serum-free media, many publications describe culturing BEAS-2B in fetal bovine serum (FBS)-containing media. The objective of this study was to define the effects of FBS on BEAS-2B cells. FBS exposure resulted in increased nuclear levels of transcription factors responsible for regulating epithelial-mesenchymal transition (EMT), increased cell invasiveness and increased anchorage-independent growth. FBS-exposed BEAS-2B cells exhibited a decrease of the epithelial markers, E-cadherin and claudin-1 at the mRNA and protein levels, along with a corresponding increase of the mesenchymal marker, vimentin, at the protein level. Fractionation studies implicated an active moiety in FBS with a molecular weight larger than 30 kD. The mesenchymal phenotype was persistent provided FBS exposure was maintained. Upon FBS removal, both epithelial and mesenchymal markers began to revert toward an epithelial phenotype. Transforming growth factor ß1 (TGFß1) exposure to BEAS-2B recapitulated some key features of FBS-induced EMT. Our data suggest that FBS-exposed BEAS-2B cells do not accurately model the epithelial phenotype. Interpretation of data from BEAS-2B should include careful consideration of the effect of culture conditions.

Breeding policies and management of pedigree dogs in 15 national kennel clubs.

To improve the health and welfare of pedigree dogs, national kennel clubs (KCs) are key players in the governance and regulation of dog breeding. In a survey conducted to investigate differences between KCs in breeding policies and management of pedigree dogs, a questionnaire was completed by 15 KCs from 11 European countries (Austria, Belgium, Denmark, France, Germany, Ireland, Latvia, The Netherlands, Norway, Sweden and the United Kingdom) and four non-European countries (Australia, Mexico, Uruguay and the USA). The most important concerns reported by KCs were exaggerated morphological features and inherited disorders. A wide variety of information, tools and strategies was used to address these issues, with implementation differing across countries and breeds. KCs reported progress in the collection and provision of information related to canine health and welfare. Implementation of advanced breeding tools, such as genetic evaluation and online advisory mating tools, and balanced breeding strategies, endorsed by clubs and breeders, remain challenging and require further development.

Heritability of patellar luxation in the Chihuahua and Bichon Frise breeds of dogs and effectiveness of a Swedish screening programme.

Patellar luxation is one of the more common orthopaedic diseases of dogs and is relatively frequent in some toy breeds, including the Chihuahua and Bichon Frise. Using data provided by the Swedish Kennel Club, genetic parameters, including heritability, were estimated for patellar luxation in the Chihuahua from 1999 to 2014 and in the Bichon Frise from 1997 to 2014. The effects of the current screening programmes for patellar luxation in these breeds were evaluated. Patellar luxation was defined as a binary trait, treating dogs as affected or unaffected. The edited data included 7024 records for the Chihuahua and 1071 records for the Bichon Frise. Patellar luxation was analysed using mixed linear and threshold animal models, including fixed effects of sex, birth month, birth year, age at veterinary examination, random effects of the examining veterinary surgeon, genetic effect of the individual and residual. The prevalence of patellar luxation was 23% in the Chihuahua and 12% in the Bichon Frise. Using threshold analysis, estimated heritabilities were 0.25 for the Chihuahua and 0.21 for the Bichon Frise on the observable scale, and 0.46 for the Chihuahua on the underlying scale. It was concluded that there is genetic variation in patellar luxation and that there has been a slight genetic improvement over the study period in the Chihuahua. Further genetic progress would be facilitated by selection using estimated breeding values based on veterinary screening records.

In vivo virulence of Mycobacterium tuberculosis depends on a single homologue of the LytR-CpsA-Psr proteins.

LytR-cpsA-Psr (LCP) domain containing proteins fulfil important functions in bacterial cell wall synthesis. In Mycobacterium tuberculosis complex (Mtbc) strains, the causative agents of tuberculosis (TB), the genes Rv3484 and Rv3267 encode for LCP proteins which are putatively involved in arabinogalactan transfer to peptidoglycan. To evaluate the significance of Rv3484 for Mtbc virulence, we generated a deletion mutant in the Mtbc strain H37Rv and studied its survival in mice upon aerosol infection. The deletion mutant failed to establish infection demonstrating that Rv3484 is essential for growth in mice. Following an initial phase of marginal replication in the lungs until day 21, the Rv3484 deletion mutant was almost eliminated by day 180 post-infectionem. Interestingly, the mutant also showed higher levels of resistance to meropenem/clavulanate and lysozyme, both targeting peptidoglycan structure. We conclude that Rv3484 is essential for Mtbc virulence in vivo where its loss of function cannot be compensated by Rv3267.

Genetic correlations of hip dysplasia scores for Golden retrievers and Labrador retrievers in France, Sweden and the UK.

In order to reduce the prevalence of inherited diseases in pedigree dogs, the feasibility of implementation of an international breeding program was investigated. One prerequisite is a strong genetic correlation between countries and our objective was to estimate this correlation for canine hip dysplasia (HD) across three countries to evaluate the feasibility of an international genetic evaluation. Data were provided by the Société Centrale Canine (SCC, France), Svenska Kennelklubben (SKK, Sweden) and The Kennel Club (KC, UK) on Golden retriever and Labrador retriever dogs. Trivariate analysis on the three different modes of scoring HD in France, Sweden and the UK was performed using a mixed linear animal model. Heritability, genetic correlation, number of common sires, genetic similarity, selection differentials and accuracy of selection were calculated. The estimated heritabilities of Golden retrievers (Labrador retrievers) for HD scores were 0.28 (0.15), 0.28 (0.29) and 0.41 (0.34) in France, Sweden and the UK, respectively. The feasibility of performing a genetic evaluation of HD across countries was indicated by the favourable genetic correlations estimated between score modes (ranged from 0.48 to 0.99). The accuracy of selection for the most recent birth year cohorts of male dogs was not improved by international evaluation compared to national evaluation. Improvement in genetic progress can however be achieved by selection across populations in different countries, particularly for small populations, which were indicated by the large difference between selection differentials based on the national and international evaluations.

Merging pedigree databases to describe and compare mating practices and gene flow between pedigree dogs in France, Sweden and the UK.

Merging pedigree databases across countries may improve the ability of kennel organizations to monitor genetic variability and health-related issues of pedigree dogs. We used data provided by the Société Centrale Canine (France), Svenska Kennelklubben (Sweden) and the Kennel Club (UK) to study the feasibility of merging pedigree databases across countries and describe breeding practices and international gene flow within the following four breeds: Bullmastiff (BMA), English setter (ESE), Bernese mountain dog (BMD) and Labrador retriever (LBR). After merging the databases, genealogical parameters and founder contributions were calculated according to the birth period, breed and registration country of the dogs. Throughout the investigated period, mating between close relatives, measured as the proportion of inbred individuals (considering only two generations of pedigree), decreased or remained stable, with the exception of LBR in France. Gene flow between countries became more frequent, and the origins of populations within countries became more diverse over time. In conclusion, the potential to reduce inbreeding within purebred dog populations through exchanging breeding animals across countries was confirmed by an improved effective population size when merging populations from different countries.

Opportunities for international collaboration in dog breeding from the sharing of pedigree and health data.

Pooling of pedigree and phenotype data from different countries may improve the accuracy of derived indicators of both genetic diversity and genetic merit of traits of interest. This study demonstrates significant migration of individuals of four pedigree dog breeds between Sweden and the United Kingdom. Correlations of estimates of genetic merit (estimated breeding values, EBVs) for the Fédération Cynologique Internationale and the British Veterinary Association and Kennel Club evaluations of hip dysplasia (HD) were strong and favourable, indicating that both scoring schemes capture substantially the same genetic trait. Therefore pooled use of phenotypic data on hip dysplasia would be expected to improve the accuracy of EBV for HD in both countries due to increased sample data.

Efficient selection against categorically scored hip dysplasia in dogs is possible using best linear unbiased prediction and optimum contribution selection: a simulation study.

Breeding to reduce the prevalence of categorically scored hip dysplasia (HD), based on phenotypic assessment of radiographic hip status, has had limited success. The aim of this study was to evaluate two selection strategies for improved hip status: truncation selection based on phenotypic record versus best linear unbiased prediction (BLUP), using stochastic simulation and selection scenarios resembling those in real dog populations. In addition, optimum contribution selection (OCS) was evaluated. Two traits were considered: HD (as a categorical trait with five classes and a heritability of 0.45 on the liability scale) and a continuous trait (with a heritability of 0.25) intended to represent other characteristics in the breeding goal. A population structure mimicking that in real dog populations was modelled. The categorical nature of HD caused a considerably lower genetic gain compared to simulating HD as a continuous trait. Genetic gain was larger for BLUP selection than for phenotypic selection in all scenarios. However, BLUP selection resulted in higher rates of inbreeding. By applying OCS, the rate of inbreeding was lowered to about the same level as phenotypic selection but with increased genetic improvement. For efficient selection against HD, use of BLUP breeding values should be prioritized. In small populations, BLUP should be used together with OCS or similar strategy to maintain genetic variation.

Automated image analysis of hand radiographs reveals widened joint spaces in patients with long-term control of acromegaly: relation to disease activity and symptoms.

OBJECTIVE: Arthropathy is an invalidating complication of acromegaly. Although acromegalic arthropathy shares features with primary osteoarthritis, joint spaces are widened rather than narrowed in patients with long-term cure of acromegaly. The late effects of acromegaly on hand joints have not been characterized. Therefore, the objective of the current study was to assess joint space widths (JSWs) of hand joints in patients with long-term control of acromegaly and to identify factors associated with JSW. METHODS: A cross-sectional study was carried out in 89 patients (age 58 ± 12 years, 49% women) with long-term controlled acromegaly and 471 controls without hand symptoms (age 46 ± 12 years, 42% women). Radiological JSWs of individual hand joints were measured by automated image analysis. RESULTS: Patients had wider mean joint spaces than controls: metacarpo-phalangeal (MCP) joints were ~24%, proximal interphalangeal joints ~21%, and distal interphalangeal joints were ~20% wider (patients vs controls; P < 0.001 for all joints). Mean JSW exceeded the 95th percentile of the values obtained in controls in 64% of patients. Higher IGF1 and GH concentrations at diagnosis were associated with larger JSWs (adjusted ß for pretreatment GH in tertiles: 0.09 (95% confidence interval (CI) 0.03-1.84) and for IGF1 in tertiles: 0.14 (95% CI 0.05-0.23) at the MCP joints in acromegalic patients. In male patients, but not in female patients, increased JSWs were associated with more self-reported pain (P = 0.02). CONCLUSIONS: Using a new semi-automated image analysis of hand radiographs, acromegalic patients with long-term disease control appeared to have increased joint spaces of all hand joints. JSWs were positively related to disease activity at diagnosis, but not to duration of follow-up, suggesting irreversible cartilage hypertrophy. Irreversible cartilage hypertrophy may partly explain persisting hand complaints despite long-term disease control.

Validity of joint space width measurements in hand osteoarthritis.

OBJECTIVE: To investigate the validity of joint space width (JSW) measurements in millimeters (mm) in hand osteoarthritis (OA) patients by comparison to controls, grading of joint space narrowing (JSN), and clinical features. METHODS: Hand radiographs of 235 hand OA patients (mean age 65 years, 83% women) and 471 controls were used. JSW was measured with semi-automated image analysis software in the distal, proximal interphalangeal and metacarpal joints (DIPJs, PIPJs and MCPJs). JSN (grade 0-3) was assessed using the osteoarthritis research society international (OARSI) atlas. Associations between the two methods and clinical determinants (presence of pain, nodes and/or erosions, decreased mobility) were assessed using Generalized Estimating Equations with adjustments for age, sex, body mass index (BMI) and mean width of proximal phalanx. RESULTS: JSW was measured in 5631 joints with a mean JSW of 0.98 mm (standard deviation (SD) 0.21), being the smallest for DIPJs (0.70 (SD 0.25)) and largest for MCPJs (1.40 (SD 0.25)). The JSN=0 group had a mean JSW of 1.28 mm (SD 0.34), the JSN=3 group 0.17 mm (SD 0.23). Controls had larger JSW than hand OA patients (P-value<0.001). In hand OA, females had smaller JSW than men (ß -0.08, (95% confidence interval (95% CI) -0.15 to -0.01)) and lower JSW was associated with the presence of pain, nodes, erosions and decreased mobility (adjusted ß -0.21 (95% CI -0.27, -0.16), -0.37 (-0.40, -0.34), -0.61 (-0.68, -0.54) and -0.46 (-0.68, -0.24) respectively). These associations were similar for JSN in grades. CONCLUSION: In hand OA the quantitative JSW measurement is a valid method to measure joint space and shows a good relation with clinical features.

Genetic variation and genetic trends in hip and elbow dysplasia in Swedish Rottweiler and Bernese Mountain Dog.

The aim of this study was to estimate genetic parameters and genetic trends for hip (HD) and elbow dysplasia (ED) in Swedish Rottweiler (RW) and Bernese Mountain Dog (BMD). Analyses were based on screening results of hip status for 14 693 RW and 8221 BMD and elbow status for 11 891 RW and 7963 BMD, as well as pedigree data for 16 614 RW and 9835 BMD, recorded by the Swedish Kennel Club. Components of (co)variance and breeding values were obtained with a mixed linear animal model. The model included the fixed effects of sex, birth month, age at screening and a combined random effect of clinic and year of examination. The need to include genetic groups for phantom parents in the model was evaluated by comparison of two different models: with and without genetic groups. Estimated heritabilities for HD and ED were between 0.34 and 0.42. The genetic correlation between the traits was weak and positive for RW (r(g) = 0.23 +/- 0.05) and not different from zero for BMD (r(g) = 0.06 +/- 0.06). F-statistics of the genetic group effects were not significant, implying that genetic groups do not need to be included in the model. Genetic trends indicated a genetic improvement in both traits. However, a faster genetic progress is expected if selection is based on predicted breeding values rather than phenotype. Based on the results, a statistical model for routine prediction of breeding values for HD and ED in Swedish dogs was suggested.

A neurologic syndrome in Golden Retrievers presenting as a sensory ataxic neuropathy.

BACKGROUND: A sensory ataxic neuropathy has been observed in Swedish Golden Retrievers recently. ANIMALS: Twenty-one affected Golden Retrievers. METHODS: Clinical and neurologic status, electrophysiologic, and pathologic status as well as pedigree analyses were evaluated. RESULTS: Clinical signs had an insidious onset between 2 and 8 months of age and a slowly progressive course. Affected dogs were ataxic and dysmetric. They had abnormal postural reactions and decreased spinal reflexes but no apparent muscle atrophy. Clinical pathology, radiography, and electrophysiology of motor systems were all within reference values. Sensory nerve conduction results of affected dogs were significantly different from those of a group of control dogs. Necropsy revealed a chronic progressive central and peripheral sensorimotor axonopathy; the proprioceptive pathways were most severely affected. CONCLUSIONS AND CLINICAL IMPORTANCE: This disease in these Golden Retrievers is distinct from other canine breed-related neurodegenerative diseases or hereditary neurodegenerative diseases described in humans. Pedigree analyses indicated a hereditary background, but the mode of inheritance could not be established.

Oxygen status of lung granulomas in Mycobacterium tuberculosis-infected mice.

It is often assumed that Mycobacterium tuberculosis (Mtb)-induced granulomatous lesions, particularly those undergoing central caseation, are anoxic, and that the survival of Mtb in these lesions requires the integrity of its non-oxidative respiratory pathways. Using the hypoxia marker pimonidazole, we now provide immunohistochemical evidence that in the most frequently used animal model system of inbred mice Mtb-induced granulomas, even after more than one year of aerogenic infection, are not severely hypoxic. In contrast, chronic aerosol infection with M. avium strain TMC724 was associated with hypoxia surrounding necrotizing granuloma centres. Direct measurements of oxygen tension with a flexible microelectrode in mouse lungs chronically infected with Mtb disclosed a wide range of oxygen partial pressures in different parts of the lungs which, however, rarely approached the anoxic conditions consistently found in necrotizing tumours. We further show that an Mtb mutant, defective in nitrate reductase (narG) necessary for survival under anaerobic conditions in vitro, can persist in the lungs of chronically infected mice to a similar extent as wild-type Mtb. These findings have important implications for the use of the mouse model of Mtb infection in developing eradication chemotherapy and for evaluating putative mechanisms of chronic persistence and latency of Mtb.

How do stroke patients fare when discharged straight to their homes? A controlled study on the significance of hospital follow-up after one month.

In our experience, stroke patients discharged straight to their homes sometimes showed marked deterioration. We investigated whether this negative course of events could be prevented by means of follow-up visits entailing extensive testing and resultant measures one month after discharge. The patients in our study included a selection of mild cases with a short length of hospital stay. Forty-six patients returned to the stroke unit on a follow-up visit, and 49 patients made up the control group. The groups were compared after 3 months, by means of questionnaires. The results did not show any definite difference between the groups. However, after 3 months we detected depressions in 13 patients in the study group and in 11 patients in the control group, most of them untreated. The study points to a need for follow-up aimed specifically at detecting depression.

Influence of Airbags and Seatbelt Pretensioners on AIS1 Neck Injuries for Belted Occupants in Frontal Impacts.

AIS1 neck injuries are the most frequent disabling injuries among car occupants in road traffic accidents. Although neck injury is mostly regarded as resulting from rear end collisions, almost one third of all neck injuries occur in frontal impacts. Several studies have shown the effect of airbags on injury and fatality rates. However, studies of the effect of airbags on the risk of injuries to different body regions are rare. Airbags and seatbelt pretensioners may influence especially the risk of neck injuries. This paper presents influence of airbags and pretensioners on reported neck injury risk in frontal impacts. Cars fitted with airbags in combination with pretensioners and cars without have been analysed. Since 1992, approximately 150,000 vehicles on the Swedish market have been equipped with crash pulse recorders to measuring frontal impacts. This study includes results from 158 frontal impacts, where the crash pulses have been recorded using crash pulse recorders and where the status of airbag deployments was known. Only reported neck injuries, often denoted as short-term disability to the neck, were considered in this study. Injury risk functions for cars with and without airbags versus change of velocity and mean and peak accelerations were analysed. It was found that airbags in combination with seat belt pretensioners reduced the number of AIS1 neck injuries in frontal impacts with 41% +/- 15.2%. In impacts at a change of velocity between 1 and 30 km/h, airbags and pretensioners was found to reduce the neck injury risk with 59% +/- 18.6%.

Innovative low-risk maternity clinic. Family physicians provide care in Calgary.

PROBLEM BEING ADDRESSED: Because some family physicians choose to stop providing maternity care, many women and their physicians have to seek this care from other providers. These providers must respect family physicians' relationships with patients and the necessity of returning the family to the referring physician for primary care after appropriate maternity and newborn care has been provided. OBJECTIVE OF PROGRAM: To design a clinic to address this problem and to deal with the practical issues, such as preservation of lifestyle, adequate remuneration, and avoiding litigation, family physicians face when they choose to practise obstetrics. To provide role models and training opportunities for future family physicians. MAIN COMPONENTS OF PROGRAM: Compatibility and cooperation among member physicians is essential in order to provide care to a substantial number of patients using an established protocol. A well-organized call schedule allows clinic physicians to enjoy a reasonable lifestyle. CONCLUSIONS: The clinic, established and organized by family physicians, provides family-centred maternity care for women and their families when their family physicians choose not to practise obstetrics.