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The domestic dog represents an ideal model for identifying susceptibility genes, many of which are shared with humans. In this study, we investigated the genetic contribution to individual differences in 40 clinically important measurements by a genome-wide association study (GWAS) in a multinational cohort of 472 healthy dogs from eight breeds. Meta-analysis using the binary effects model after breed-specific GWAS, identified 13 genome-wide significant associations, three of them showed experimental-wide significant associations. We detected a signal at chromosome 13 for the serum concentration of alanine aminotransferase (ALT) in which we detected four breed-specific signals. A large proportion of the variance of ALT (18.1–47.7%) was explained by this locus. Similarly, a single SNP was also responsible for a large proportion of the variance (6.8–78.4%) for other measurements such as fructosamine, stress during physical exam, glucose, and morphometric measurements. The genetic contribution of single variant was much larger than in humans. These findings illustrate the importance of performing meta-analysis after breed-specific GWAS to reveal the genetic contribution to individual differences in clinically important measurements, which would lead to improvement of veterinary medicine.

Introduction: Mitral valve area (MVA) planimetry is used to diagnose and classify mitral stenosis (MS) in humans using two-dimensional and three-dimensional echocardiography (MVA2D and MVA3D). This study aimed to evaluate agreement, feasibility, and observer variability between MVA2D and MVA3D in English Bull Terriers (BT). Our hypotheses were (1) that the MVA of BT is generally smaller than that of breeds with similar body weight and (2) that these techniques could be used to diagnose MS in BTs. Animals: Twenty healthy BTs, 15 healthy Boxers, and 49 BTs with heart disease. Materials and methods: A prospective diagnostic agreement study was conducted. All dogs underwent a thorough clinical examination, conventional transthoracic echocardiography, and three-dimensional echocardiography. Results: Bland–Altman plots (limits of agreement: 0.12–1.5) showed consistent bias and poor agreement between MVA2D and MVA3D. For the 69 BTs, MVA3D (2.1 ± 0.50 cm2) measurements were significantly lower than MVA2D measurements (2.9 ± 0.60 cm2), and healthy BTs had significantly lower MVA parameters than healthy Boxers (p < 0.001). Intraobserver and interobserver variability were excellent for both MVA2D and MVA3D (intraclass correlation coefficient >0.9). Six BTs were diagnosed with MS, with MVA3D less than 1.8 cm2 and a mean transmitral gradient (MTG) of more than 5 mmHg. Conclusions: Both MVA2D and MVA3D are feasible, have low observer variability and can be used to diagnose MS in BTs. For assessing the narrowest orifice area, the preferred method is MVA3D. The smaller MVA in BTs compared to Boxers may indicate some degree of MS.

The left ventricular systolic longitudinal function, traditionally measured by M-mode-derived mitral annular plane systolic excursion (MAPSE), is reduced in feline hypertrophic cardiomyopathy (HCM) and further reduced in cats with left-sided congestive heart failure (CHF). The objectives of this study were to compare longitudinal displacement measured by tissue tracking (TT-LD) and MAPSE in feline HCM and assess these methods' ability to differentiate CHF from preclinical HCM. A further objective was to provide preliminary reference intervals for TT-LD.Eighty-five client-owned cats.A retrospective case-control study. Anatomical M-mode was used to record MAPSE, and TT-LD was recorded by tissue tracking.Reduced longitudinal displacement measured by either MAPSE or TT-LD was significantly associated with CHF in cats with HCM (p 0.036). Receiver-operating characteristic analysis indicated that TT-LD (AUC: 92.9%-97.9%) was more sensitive and specific than MAPSE (AUC: 85.8%-89.1%) for the detection of CHF. A diagnostic cut-off of 2.89 mm for maximal TT-LD in the left ventricular septum resulted in a sensitivity and specificity of 100% and 83.3%, while a diagnostic cut-off of 2.41 mm in the left ventricular posterior wall resulted in a sensitivity of 100% and a specificity of 90%.M-mode-derived mitral annular plane systolic excursion and TT-LD were strongly correlated, but not interchangeable. Longitudinal displacement measured by tissue tracking decreased more with disease severity than traditional MAPSE. Longitudinal displacement may help detect CHF in cats with HCM - with the maximal TT-LD of the left ventricular posterior wall achieving the highest AUC value.

Background Heart failure (HF) is associated with changes in inflammatory and oxidative stress biomarkers. This study aimed to evaluate the changes of a panel of inflammatory and oxidative stress biomarkers in dogs with different stages of HF and its relation with the severity of the disease and echocardiographic changes. A total of 29 dogs with HF as a result of myxomatous mitral valve degeneration or dilated cardiomyopathy were included and classified as stage-A (healthy), B (asymptomatic dogs), C (symptomatic dogs) and D (dogs with end-stage HF) according to the ACVIM staging system. In these dogs an ecnhocardiographic examination was performed and cytokines, and inflammatory and oxidative stress markers were evaluated in serum. Results KC-like was significantly increased in dogs of stage-C (P P P P P Conclusion Our results showed that dogs with advanced HF show increases in positive acute-phase proteins and selected inflammatory cytokines such as KC-like, and decreases in antioxidant biomarkers, indicating that inflammation and oxidative stress act as collaborative partners in the pathogenesis of HF. Some of these biomarkers of inflammation and oxidative stress could have the potential to be biomarkers to monitor the severity of the disease and the effect of treatment.

BACKGROUND Cardiogenic embolism (CE) in cats is a devastating condition primarily associated with hypertrophic cardiomyopathy (HCM). Hypercoagulability may pose a risk for thrombus formation; however, no single test can predict CE development. Platelet microparticles (PMPs) released from platelet membranes are associated with thrombosis in humans. OBJECTIVES The aims were to validate flow cytometric PMP quantification in cats analytically and, in a pilot study, evaluate the procoagulant annexin V (AnV) positive PMP concentration in healthy cats and cats with asymptomatic HCM. METHODS With CD61 as a platelet marker, CD61+ AnV+ PMPs (0.3-1.0 μm) were quantified in citrated whole blood (WB) and platelet-poor plasma (PPP) using flow cytometry. Analyses were performed in 6 healthy cats and 5 cats with asymptomatic HCM. The coefficient of variation (CV) for duplicate (intra-assay) and parallel (inter-assay) analyses were calculated. RESULTS PMP concentrations were quantified with acceptable intra-assay CV for WB (CD61+ /AnV- ; 2.4%, 0.2%-8.4% (median, range), CD61+ /AnV+ ; 3.8%, 0.1%-12.5%) and PPP (CD61+ /AnV- ; 5.0%, 0.7%-12.8%, CD61+ /AnV+ ; 7.4%, 0.5%-15.3%), and acceptable inter-assay CV for WB in 10/11 cats (CD61+ /AnV- ; 6.2%, 1.4%-13.3%, CD61+ /AnV+ ; 6.4%, 0.7%-17.2%), but unacceptable for PPP (CD61+ /AnV- ; 15.6%, 5.8%-42.7%, CD61+ /AnV+ ; 27.8%, 8.4%-77.1%). For WB PMP concentrations, the pilot data demonstrated no differences between healthy cats and cats with asymptomatic HCM (4/5 with left ventricular outflow obstruction) for either the CD61+ /AnV- or the CD61+ /AnV+ PMPs. CONCLUSIONS Only WB PMP concentrations could be quantified reliably in cats in a clinical setting. PMP concentrations did not differ between healthy and asymptomatic HCM cats in this pilot study.

Background: Symmetric dimethylarginine (SDMA) has been increasingly used as a marker of early chronic kidney disease (CKD) in cats, but little is known about the influence of comorbidities on SDMA in this species. Hypothesis: Hypertrophic cardiomyopathy (HCM) and diabetes mellitus (DM), independently of CKD, are associated with changes in serum SDMA. Animals: Ninety-four cats (17 with CKD, 40 with HCM, 17 with DM, and 20 healthy controls). Methods: Case-control study. Clinical examination, echocardiography, ECG, blood pressure, CBC, biochemistry, thyroxine, and SDMA measurement were performed. Urinalysis was performed in controls and cats with CKD and DM. Analysis of variance was used to compare overall differences in the log-transformed SDMA data among groups. A random forest algorithm was applied to explore which clinical and other factors influenced serum SDMA. Results: Median (range) serum SDMA for the renal group (positive control) was 19 (10–93) μg/dL, whereas for the control group (negative control), it was 10 (5–15) μg/dL. For the cardiac and diabetic groups, serum SDMA was 9 (4–24) μg/dL and 7 (3–11) μg/dL, respectively. The renal group had significantly higher SDMA concentrations and the diabetic group significantly lower SDMA concentrations compared to all other groups. Conclusions and Clinical Importance: Serum SDMA concentrations in cats with HCM were not significantly different from those of healthy control cats. Cats with DM, however, had significantly lower SDMA concentrations than controls, a finding that needs further investigation and should be kept in mind when evaluating renal function of cats with this endocrinopathy.

ObjectivesCardiac troponins are sensitive and specific markers of myocardial injury. However, their reliability in renal disease has been questioned owing to possible renal involvement in troponin elimination. The primary objective of the present study was to examine whether serum cardiac troponin I is elevated in cats with compromised renal function and no clinically relevant structural cardiac disease. A secondary objective was to examine whether cardiac troponin I is measurable in the urine of cats with normal and compromised renal function.MethodsThis prospective case-control study included 52 cats (19 with compromised renal function, 19 with primary cardiac disease and 14 healthy controls). For all cats, clinical examination, echocardiography, electrocardiography, blood pressure, complete blood count, biochemistry, serum thyroxine and urinalysis were performed. Cardiac troponin I was measured in the serum and urine of each cat.ResultsMedian (range) serum cardiac troponin I concentrations were 0.052 ng/ml (0.015–0.78 ng/ml) for the renal group, 0.083 ng/ml (0.003–3.27 ng/ml) for the cardiac group and 0.012 ng/ml (0.003–0.14 ng/ml) for the control group. The renal and cardiac groups both had significantly higher serum cardiac troponin I concentrations than the control group, whereas no difference could be detected between the renal and cardiac groups. In the renal group 7/19 cats had measurable urine cardiac troponin I, whereas cardiac troponin I was measurable in the urine of one cat in the cardiac group and two healthy controls. There was no significant correlation between serum and urine cardiac troponin I.Conclusions and relevanceElevated serum cardiac troponin I in cats with compromised renal function may occur without evidence of clinically relevant structural cardiac disease. Moreover, detecting cardiac troponin I in urine is most likely in cats with compromised renal function.

Cardiovascular lesions are commonly diagnosed postmortem in scarlet ibis (

Myxomatous mitral valve disease (MMVD) induces progressive left atrial (LA) enlargement. The LA modulates left ventricular filling and performance through its reservoir, conduit, and contractile function. Assessment of LA size and function may provide valuable information on the level of cardiac compensation. Left atrial function in dogs with naturally occurring MMVD remains largely unexplored. The objective of this study was to evaluate LA volume and function in dogs with naturally occurring MMVD.This prospective study included 205 client-owned dogs of different breeds, 114 healthy dogs, and 91 dogs with MMVD of different disease severities.Using two-dimensional echocardiography, the biplane area-length method was applied to assess LA volume and calculate volumetric indices of LA reservoir, conduit, and contractile function.Left atrial volume and LA stroke volume increased, whereas LA reservoir and contractile function decreased with increasing disease severity. A maximal LA volume2.25mL/kg was the optimal cut off identified for excluding congestive heart failure in dogs with chronic MMVD with a sensitivity of 96% and a specificity of 100%. An active LA emptying fraction24% and/or a LA expansion index126% were suggestive of congestive heart failure in dogs with chronic MMVD with a sensitivity of 77% and a specificity of 89% and a sensitivity of 82% and a specificity of 82%, respectively.Dogs with MMVD appear to have larger LA volumes with poorer LA function. Deteriorating LA function, characterized by a decreasing reservoir and active contractile function, was evident in dogs with MMVD with increasing disease severity.

Objectives To compare a linear and three volume-based two-dimensional echocardiographic methods for measuring LA size: left atrium to aorta ratio (LA/Ao ratio), biplane area-length, biplane modified Simpson and monoplane area-length. Animals One hundred seventy-six client-owned dogs of different breeds, 88 healthy dogs and 88 dogs with myxomatous mitral valve disease of different disease severity. Methods The left apical four- and two-chamber views were used to measure LA volumes. The right parasternal short-axis view at the level of the heart base was used to measure the LA/Ao ratio. Results The biplane area-length method yielded 2.8% larger values than those of the biplane modified Simpson method, consistent across the full range of LA volumes. The monoplane area-length method derived on average 5.8% larger values of LA volume than the biplane area-length method. The difference between these two methods was most pronounced at larger LA volumes. The relation between the LA/Ao ratio and LA volume was curvilinear and with increasing LA size these two methods derived very dissimilar values. Conclusions All methods showed good feasibility and reproducibility, with the volume-based methods having the most favourable intra- and inter-observer variabilities. The LA/Ao ratio underestimates at higher values of LA size compared to the biplane area-length method. LA volume methods may be superior to the LA/Ao ratio in quantification of LA size. The biplane area-length method and biplane modified Simpson method can be used interchangeably. The monoplane area-length measurement may be used as a quick and reliable method for assessment of LA size in clinical practice.

To investigate the prevalence and amplitudes of the electrocardiographic J wave in the Petit Basset Griffon Vendeen compared to 10 other dog breeds.Electrocardiograms from 206 healthy dogs representing 11 dog breeds were included in the study. Besides Petit Basset Griffon Vendeen (PBGV; n = 23) 10 other dog breeds were included.An electrocardiogram ruler was used for measuring the amplitudes of the J waves. The definition of a J wave was a positive deflection at the J point of ≥0.1 mV in more than 1 lead of the bipolar standard limb leads (I, II, III) or the unipolar standard limb leads (aVL and aVF).The prevalence of J waves in the PBGV (n = 23) was 91% (n = 21, standard error (SE) = 5.9%), which was significantly higher compared to seven other dog breeds (p

OBJECTIVES: A missense mutation (A31P) in the cardiac myosin binding protein C gene has been associated with hypertrophic cardiomyopathy (HCM) in Maine Coon cats. The aim of this study was to investigate the effect of A31P on development of HCM, myocardial diastolic dysfunction detected by color tissue Doppler imaging and occurrence of cardiac death during longitudinal follow-up in a cohort of Maine Coon cats.ANIMALS: The original cohort comprised 282 cats (158 of wild-type genotype, 99 heterozygous for A31P and 25 homozygous for A31P).METHODS: Prospective longitudinal study including echocardiography and registration of survival.RESULTS: The median age at the initial examination was 1.7 years (range, 0.8-9.2 years) and 6.4% (18/282) of the cats were diagnosed with HCM. One hundred sixty-five cats were eligible for echocardiographic re-examination, and during an average follow-up period of 2.7 years an additional 6.7% (11/165) of the cats developed HCM. Survival data could be obtained for 262 of the cats originally included, and among these 9.2% (24/262) died of causes that met the study criteria for cardiac death. In the homozygous group 80% (20/25) of cats included were diagnosed with HCM and 48% (12/25) suffered cardiac death during follow-up. These results corresponded to a significantly higher risk for cats homozygous for A31P to develop HCM (pCONCLUSIONS: Homozygosity for A31P was associated with a high penetrance of HCM and a substantial risk for cardiac death in the study population.

Mitochondrial dysfunction and oxidative stress are important players in the development of various cardiovascular diseases, but their roles in hypertrophic cardiomyopathy (HCM) remain unknown. We examined whether mitochondrial oxidative phosphorylation (OXPHOS) capacity was impaired with enhanced mitochondrial oxidative stress in HCM. Cardiac and skeletal muscles were obtained from 9 domestic cats with spontaneously occurring HCM with preserved left ventricular systolic function and from 15 age-matched control cats. Mitochondrial OXPHOS capacities with nonfatty acid and fatty acid substrates in permeabilized fibers and isolated mitochondria were assessed using high-resolution respirometry. ROS release originating from isolated mitochondria was assessed by spectrofluorometry. Thiobarbituric acid-reactive substances were also measured as a marker of oxidative damage. Mitochondrial ADP-stimulated state 3 respiration with complex I-linked nonfatty acid substrates and with fatty acid substrates, respectively, was significantly lower in the hearts of HCM cats compared with control cats. Mitochondrial ROS release during state 3 with complex I-linked substrates and thiobarbituric acid-reactive substances in the heart were significantly increased in cats with HCM. In contrast, there were no significant differences in mitochondrial OXPHOS capacity, mitochondrial ROS release, and oxidative damage in skeletal muscle between groups. Mitochondrial OXPHOS capacity with both nonfatty acid substrates and fatty acid substrates was impaired with increased mitochondrial ROS release in the feline HCM heart. These findings provide new insights into the pathophysiology of HCM and support the hypothesis that restoration of the redox state in the mitochondria is beneficial in the treatment of HCM.

The increasing incidence of orthopaedic methicillin-resistant Staphylococcus aureus (MRSA) infections represents a significant therapeutic challenge. Being effective against MRSA, the role of vancomycin may become more important in the orthopaedic setting in the years to come. Nonetheless, vancomycin bone and soft tissue penetration during infection remains unclear. In eight pigs, implant-associated osteomyelitis was induced on day 0, using a Staphylococcus aureus strain. Following administration of 1,000 mg of vancomycin on day 5, vancomycin concentrations were obtained with microdialysis for 8 h in the implant bone cavity, in cancellous bone adjacent to the implant cavity, in subcutaneous adipose tissue (SCT) adjacent to the implant cavity, and in healthy cancellous bone and healthy SCT in the contralateral leg. Venous blood samples were also obtained. The extent of infection and inflammation was evaluated by post-mortem computed tomography scans, C-reactive protein serum levels and cultures of blood and swabs. In relation to all the implant cavities, bone destruction was found. Ranging from 0.20 to 0.74, tissue penetration, expressed as the ratio of the area under the concentration-time curve from 0 to the last measured value, was incomplete for all compartments except for healthy SCT. The lowest penetration was found in the implant cavity. In conclusion, Staphylococcus aureus implant-associated osteomyelitis was found to reduce vancomycin bone penetration, especially in the implant cavity. These findings suggest that it may be unsafe to rely solely on vancomycin therapy when treating acute osteomyelitis. Particularly when metaphyseal cavities are present, surgical debridement seems necessary. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1093-1098, 2018.

Treatment of post-traumatic and implant-associated osteomyelitis (IAO) includes surgical debridement, removal of implants and long-term antibiotic therapy. The success of antibiotic therapy relies not only on activity towards the infecting pathogen, but also on sufficient penetration of the target site. The aim of the present study was to characterize the local pathological changes associated with reduced penetration of cefuroxime to infected bone implant cavities. Previously, reduced penetration of systemically administrated cefuroxime was demonstrated in the implant cavity of 10 pigs with Staphylococcus aureus IAO present for 5 days. In the present study, a comprehensive histopathological characterization of the peri-implant bone tissue was performed and correlated with the reduced penetration of cefuroxime. In two pigs, the levels of oxygen, pyruvate and lactate was estimated in the implant cavity. A peri-implant pathological bone area (PIBA) developed with a width of 1.2 up to 3.8 mm. PIBAs included: (1) suppuration, resulting in destruction of the implant cavity contour, and (2) a non-vascular zone of primarily necrotic bone tissue. A strong negative correlation was seen between PIBA width and cefuroxime area under the concentration time curves (AUC[0-last]) and peak concentration of cefuroxime (Cmax). All metabolic measurements demonstrated hypoxia. In conclusion, subacute suppurative bone inflammation with local tissue destruction can result in decreased penetration of antibiotics and insufficient oxygen supply.

Background Myocardial injury detected by cardiac troponin I and T (cTnI and cTnT) in cardiac disease is associated with increased risk of death in humans and dogs. Hypothesis Presence of myocardial injury predicts long-term death in cats with hypertrophic cardiomyopathy (HCM), and ongoing myocardial injury reflects change in left ventricular wall thickness over time. Animals Thirty-six cats with primary HCM. Methods Prospective cohort study. Cats with HCM were included consecutively and examined every 6 months. Echocardiography, ECG, blood pressure, and serum cTnI and cTnT were evaluated at each visit. Cox proportional hazards regression analysis was performed to evaluate prognostic potential of serum troponin concentrations at admission and subsequent examinations. Correlations were used to examine associations between troponin concentrations and cardiac hypertrophy. Results Troponin concentrations at admission were median [range] 0.14 [0.004–1.02] ng/mL for cTnI, and 13 [13–79.5] ng/L for cTnT. Both were prognostic for death (P = .032 and .026) as were the last available concentrations of each (P = .016 and .003). The final cTnT concentration was a significant predictor of death even when adjusting for the admission concentration (P = .043). In a model containing both markers, only cTnT remained significant (P = .043). Left ventricular free wall thickness at end-diastole (LVFWd) at admission was correlated with cTnI at admission (r = 0.35, P = .035), however no significant correlations (r = 0.2–0.31, P = .074–.26) were found between changes in troponin concentrations and left ventricular thickness over time. Conclusions and Clinical Importance Myocardial injury is part of the pathophysiology leading to disease progression and death. Low sensitivities and specificities prevent outcome prediction in individual cats.

Cardiovascular lesions are commonly diagnosed postmortem in scarlet ibis (Eudocimus ruber), but antemortem diagnosis is rare. The aim of this study was to evaluate the cardiovascular health of a zoo population (n = 44) of apparently healthy, adult, scarlet ibis. A cross-sectional study design was employed whereby each animal was manually restrained for physical examination, phlebotomy, and echocardiographic examination performed with a 12-MHz transducer and a ventromedial approach, and observed intervals were calculated for 12 parameters. Seven individuals from the study population had high left-sided mid-ventricular velocities (2.59-5.89 m/sec) compared with values in other species. Follow-up examination suggested that these mid-ventricular obstructive lesions were dynamic and transient in nature rather than caused by fixed lesions within the outflow tract and may therefore be associated with stress. Conscious echocardiography proved to be feasible, although, unsurprisingly, the stress response in nonhabituated birds appeared to increase blood flow velocities. Handling protocols likely have a significant effect on echocardiographic parameters and should be taken into consideration when interpreting findings. Serum cholesterol concentrations were generally high (7.4-13.0 mmol/L), and further work is required to investigate the relationship between circulating cholesterol and the development of atherosclerosis in scarlet ibis. Serum cardiac troponin I concentrations were measured, and four animals were identified with suspected elevated levels, likely indicative of myocardial damage.

A coprological survey was conducted to investigate the prevalence of parasites infecting hunting dogs with no history of recent anthelmintic treatments and with no overt clinical manifestations of cardiopulmonary or gastrointestinal illness. The hunting dogs were recruited from four different areas in Denmark, and fecal samples were obtained in October and November, 2007. For detecting gastrointestinal parasites, samples (N=178) were examined by a commercial flotation kit (Fecalyzer(®) EVSCO, USA). For detection of cardiopulmonary parasites, samples (N=181) were collected on three consecutive days and examined using the Baermann method. Parasites were recovered from 22.1% of the hunting dogs: Angiostrongylus vasorum (2.2%), Toxocara canis (12.4%), Uncinaria stenocephala (7.3%), Taenia spp. (1.7%), Toxascaris leonina (0.6%), Coccidia (0.6%) and unidentified trematode eggs (1.1%). Infection with only one species of parasite was more common (89.5%) than infection with two species (10.5%). A multiple logistic regression model showed that prevalence of intestinal parasites was not influenced by age, gender or breed in adult dogs. There was a significantly higher prevalence of intestinal parasites in the densely populated area of the island Zealand compared with the less populated regions of the peninsular Jutland. The present study reports the first case of A. vasorum in a dog from Jutland. The dog had been visiting the endemic area of western Zealand, suggesting that translocation of sub-clinically infected dogs may contribute to introduction of A. vasorum into non-endemic areas.

Hypertrophic cardiomyopathy (HCM) is a myocardial disorder, with complications including heart failure, thromboemboli and sudden death. Human and feline HCM (fHCM) are clinically comparable, thus fHCM may serve as a spontaneous animal model. fHCM in Maine Coon (MC) cats is associated with the p.A31P mutation in the cMyBP-C protein. The mutation is located in the cMyBP-C C0-domain which is known to interact with actin. The presence and levels of the wild type and mutated protein in heart tissue from mutant and wild type MC cats were examined by SDS-PAGE and mass spectrometry (MS). Quantitative yeast-2-hybrid (Y2H) protein-protein interaction analysis was used to assess the effect of the mutation on C0C1/actin interaction. The NMR-based structure of the C0 domain was used to calculate the energetic consequence of replacing alanine with a proline residue. In the homozygous MC cat, the mutated cMyBP-C protein was present, and cMyBPC-C levels were not reduced compared to that of the wild type cat. However, the interaction of actin with mutant cMyBP-C C0C1 was reduced compared to that of wild type. This may be because the substitution of the alanine with proline in position 31 was energetically highly unfavorable and resulted in only one hydrogen bond within the anti-parallel beta-strand compared to two hydrogen-bonds for alanine, possibly destabilizing the structure of the actin-interacting domain. The p.A31P mutation is present in cardiac tissue and the most likely pathogenic mechanism is interference with contractility by reducing binding of the C0C1 domain of cMyBP-C to actin.

HYPERTROPHIC cardiomyopathy (HCM) is the most common cardiac disease in cats, associated with severe myocardial structural and ultrastructural changes (Abbott 2010, Christiansen and others 2015). In human beings, HCM is frequently inherited as an autosomal dominant trait caused by mutations in genes encoding sarcomeric proteins, including the myosin-binding protein C (MYBPC3) and the cardiac troponins (Gomes and Potter 2004, Cambronero and others 2009). In cats, familial mutations have been described in the MYBPC3 protein in Maine Coons (A31P) and ragdolls (R820W) (Meurs and others 2005, 2007). Cats homozygous for these mutations have a high risk of developing a fatal, progressive HCM (Meurs and others 2005, Borgeat and others 2014b). While additional causative mutations associated with feline HCM have yet to be discovered, several other breeds are considered predisposed. Cardiac troponin I (cTnI) is a sensitive and specific marker of cardiomyocyte injury. Serum cTnI is generally increased in HCM patients and is associated with increased risk of mortality (Borgeat and others 2014a, Langhorn and others 2014). The cause of myocardial injury is believed to be mild chronic ischaemia due to a range of neurohormonal, inflammatory and vascular factors (Langhorn and others 2014). Additionally, effects of specific mutations and sex on myocardial injury in HCM have been suspected in human studies (Cambronero and others 2009, Kubo and others 2010), and one study on ragdolls similarly reported a difference in cTnI concentration between mutation-positive and mutation-negative cats (Borgeat and others 2015). The aim of this study was …

Background: Familial hypertrophic cardiomyopathy (HCM) has been described previously in British Shorthair cats (BSH), but until now, no reports have been published describing the prevalence of the disease within this breed. Objectives: The aim of this study was to assess the prevalence of HCM in a large cohort of BSH and to evaluate the effect of sex, weight, and increasing age as potential risk factors for this disease. Animals: Three hundred and twenty-nine BSH presented for routine HCM screening during a 4-year period. Methods: Prospective cross-sectional study in which all cats were screened for HCM by conventional echocardiography. Results: A total of 329 cats were examined, 214 females and 115 males, with a median age of 2.3 years (range, 0.8–14.1). Twenty-eight cats (8.5%) were classified as HCM-positive, 14 (4.3%) as equivocal, 282 (85.7%) as HCM-negative, and 5 (2.1%) were diagnosed with other cardiac diseases. The median age for diagnosis of HCM was 2.7 years (range, 0.9–14.1). Male cats had a significantly higher occurrence of HCM (20.4%) compared with the females (2.1%) corresponding to an odds ratio of 7.89 (95 % CI, 2.54–28.08) for males versus females adjusted for age and weight (P < .001). Conclusion: The BSH in our cohort had a high prevalence of HCM, often of early onset and with a significant male sex predisposition. We strongly recommend echocardiographic screening in this breed, especially cats used for breeding.

Haematological and biochemical parameters were studied prospectively in 48 dogs naturally infected with Angiostrongylus vasorum in a primary care setting. Samples for analysis were obtained when treatment was started and 42days afterwards. Prior to treatment, 21% of affected dogs exhibited eosinophilia, whereas increased total white blood cell (WBC) counts and neutrophilia were observed in only 4.2%. WBC counts and concentrations of neutrophils, eosinophils and monocytes decreased significantly from days 0 to 42, indicating that, even in dogs without elevated absolute blood values, a low grade inflammatory response may be present in dogs with A. vasorum infection. Biochemical changes (especially an increase in serum globulins and a decrease in serum fructosamine) were in agreement with the findings of other studies. The results show that the diagnosis of canine angiostrongylosis should not be excluded based on unremarkable haematological and blood biochemical parameters. They also support our recent finding that a low serum fructosamine concentration may be associated with infection with A. vasorum.

Canine pulmonary angiostrongylosis is an emerging snail-borne disease causing verminous pneumonia and coagulopathy in dogs. The parasite is found in Europe, North and South America and Africa, covering tropical, subtropical and temperate regions. Its distribution has been characterised by isolated endemic foci, with only sporadic occurrences outside these areas. In the last two decades, the literature has been dominated by several case reports and small case series describing sporadic disease in old or new endemic areas. Case reports and experimental studies with high doses of infective third stage larvae may not reflect what happens under field conditions. There is insufficient understanding of the spread of infection and the dynamic consequences of this parasite in the canine population. This review discusses the biology, epidemiology, clinical aspects and management of canine pulmonary angiostrongylosis.

Objective assessment of pulmonary disease from computed tomography (CT) examinations is desirable but difficult. When such assessments can be made, it is important that they are related to some part of the pathophysiologic process present. Herein we propose that automated volume histogram analysis can yield data that allow differentiation of normal from abnormal lung, and that the magnitude of disease will have an association with objective CT indices. Data from pulmonary CT images from 34 foxes (six uninfected controls and 28 infected with Angiostrongylus vasorum, subdivided by age and infective dose) were available. Lung tissue was segmented from surrounding tissue using an automated segmentation method. A volume histogram showing voxel frequency for each CT number in the range -1024 to -250 HU was created from the entire image stack from each fox. Using these data, the inter-quartile range and the CT number at the 95th percentile were determined. The results showed that segmentation could be readily achieved but that areas of severely diseased lung were excluded. Based on two-way analysis of variance for both the inter-quartile range and the CT number at the 95th percentile, both quantities were significantly affected by the infection status of the animal and were related to worm burden (P < 0.001). The study shows that this form of analysis is readily achieved and provides quantitative data that can be used to assess disease severity, progression, and response to treatment.

A Lulworthia-like species with affinities to Lulworthia opaca (=Halophiobolus opacus) and L. longirostris (=H. longirostris) was discovered on driftwood collected along the Danish coast and from the northwestern coast of the USA. Examination of the type material of L. opaca and L. longirostris leads to the conclusion that the two species are different at the generic level. Lulworthia longirostris shares several characters in common with the Lulworthia-like species collected in Denmark. A detailed study of the Lulworthia-like species has provided evidence for the erection of a new genus Rostrupiella to accommodate it. The new taxon is characterised by large ascomata that are deeply seated within the wood, with long necks extending through the wood to the surface, a bell-like structure protruding into the centrum, large, melanised bladder cells present in the wood cells and formation of inhibition zones in the host tissue. Partial nuclear LSU ribosomal RNA gene of Rostrupiella was sequenced to determine its phylogenetic relationship with other genera in the Lulworthiales.

Objectives This study was conducted to estimate the incidence of aortic stenosis (AS) in a group of Boxers evaluated by auscultation, ECG, blood pressure measurement and Doppler-echocardiography. Background The Boxer is a breed at significantly increased risk of AS. The prevalence of murmurs and Doppler-echocardiographic findings consistent with AS in this breed is reportedly high. Animals, materials and methods Eighty-nine Boxers were evaluated by auscultation, and final murmur grade recorded after stress testing. Doppler echocardiography was performed in fifty-five adult Boxers. Electrocardiograms (ECG, n = 53), non-invasive blood pressure measurement ( n = 32), and Holter monitoring ( n = 24) were performed in selected dogs. Degree of AS was based on the aortic peak flow velocity (Ao PFV). Final Ao PFV was recorded as the highest value obtained after stress testing. AS was defined as an Ao PFV > 2 m/s on continuous wave Doppler, using the subcostal window. Pressure gradients (Δ p ) were calculated using the modified Bernoulli equation (Δ p = 4 V 2 ). Mild AS was defined as Δ p = 16–40 mmHg, moderate AS Δ p = 40–75mmHg, and severe AS Δp > 75mmHg. Results 62% of adult Boxers evaluated by echocardiography had an Ao PFV > 2 m/s suggestive of AS. Systolic basilar ejection murmurs were diagnosed in 73%. Murmur intensity showed a statistically significant correlation with Ao PFV ( p Conclusion The study reports on systolic murmurs and Doppler-echocardiographic findings consistent with AS, as well as ECG and blood pressure measurements in a sample of pure-breed Boxers.

To meet the commitments made in Kyoto, energy-related CO 2 emissions would have to fall to almost 30% below the level projected for a "Business-As-Usual" scenario. Meeting this goal will require a large-scale shift toward climate-friendly technologies such as fuel cells, which have a large long-term potential for both stationary generation and transportation. The deployment of a technology is the last major stage in the process of technological shift. Climate-friendly technologies are not being deployed at a sufficient rate or in sufficient amount to allow IEA countries to meet their targets. Hence, if technology is to play an important roll in reducing emissions within the Kyoto time frame (2008–2012) and beyond, immediate and sustained action to accelerate technology deployment will be required. Obstacles in the way of the deployment of technologies that are ready or near-ready for normal use have come to be referred to as market barriers. The simplest yet most significant form of market barrier to a new technology is the out-of-pocket cost to the user relative to the cost of technologies currently in use. Some market barriers also involve market failure, where the market fails to take account of all the costs and benefits involved, such as omitting external environmental costs, and therefore retard the deployment of more environmentally sustainable technologies. Other barriers include poor information dissemination, excessive and costly regulations, slow capital turnover rates, and inadequate financing. Efforts by governments to alleviate market barriers play an important role to complement private-sector activities, and there are many policies and measures each government could take. In addition, international technology collaboration can help promote the best use of available R&D resources and can contribute to more effective deployment of the result of research and development by sharing costs, pooling information and avoiding duplication of efforts.

SUMMARY Objective This study investigatest the influence of sampling period duration, time of day, age, sex, body weight and degree of mitral valve prolapse (MVP) on various measures of heart rate variability (HRV) in the dog. The correlations between the HRV parameters were also investigated. Background Holter recording is increasingly being used in dogs but method studies are sparse. Previous studies suggest that canine MVP is related to a high vagal tone. Methods Twenty-four hour ambulatory electrocardiographic recording (Holter recording) was performed on 24 Dachshunds (11 males and 13 females). All dogs were between 2 and 6 years of age and without heart murmurs. Results The majority of the HRV parameters depended on the duration of the sampling period and they generally exhibited circadian variation. Higher values in males than in females were found for several parameters, especially low frequency power (LF) during 24 hour recording (P = 0.0002). Although a number of HRV parameters correlated positively with MVP severity and negatively with age, the influence of these two factors was not clear and consistent in all sampling periods. The degree of MVP related to the number of episodes of supraventrucular tachycardia occuring during the day. Generally, a large inter-individual variation was found with regard to the HRV parameters and the correlations between the parameters were weaker than correlations reported in humans. Two manually measured ECG parameter related to vagal tone correlated strongly with 2 out of 3 vagal indexes derived from the HRV analysis. Conclusion HRV parameters are influenced especially by sex and sampling period duration, but also by age and MVP status in young, clinically healthy Dachshunds.

The IEA was established after the 1973 oil shock as an independent international organization to safeguard energy supplies through collective actions between countries. One of the most important tools for doing this is the IEA technology program, which currently includes some 40 multilateral collaboration projects, called Implementing Agreements, covering most relevant technology aspects of energy supply and end use. The present IEA World Energy Outlook forecasts a continued growth in world energy demand and a continued dependence on fossil fuels as the primary fuels. Projected greenhouse gas emissions in 2010 are thus 35–50% above the 1990 level. Increased use of renewables will be necessary to change this negative trend and to reach the long-term goal of a sustainable energy system. The development of many renewables is promising but R&D efforts and market experiments must continue in order to increase their shares of total energy supply. Geothermal energy1 plays an increasingly significant rol...

Samples from the intertidal zone of mooring posts of oak standing in Svanemollen Harbour and samples from fallen oak trees lying in the waterline at Strandegaard Dyrehave were examined for the occurrence of marine lignicolous fungi. Buxetroldia bisaccata gen. et sp. nov., belonging to the Halosphaeriaceae, was encountered and is described from light microscope (LM) and SEM studies. The taxonomic position of B. bisaccata is discussed especially in relation to Tunicatispora australiensis; the main difference between the two species is found in the structure of the ascospore appendages.

The diagnostic accuracy of the urinary cortisol:creatinine ratio (CCR), with the cortisol being measured by ELISA, was evaluated by subjecting data from 18 dogs with and 20 dogs without hyperadrenocorticism to receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (W 0.93, SE(w) 0.044) was much higher than 0.5, indicating that the CCR did distinguish between dogs with and without hyperadrenocorticism. A cutoff value of about 60 x 10(-6) was associated with the highest sensitivity (1.0) and specificity (0.85). At the disease prevalence rate of the present study (0.47), the positive and negative predictive values were 0.87 and 1.0, respectively. These numbers indicate that canine hyperadrenocorticism may be safely excluded when the CCR is below 60 x 10(-6) but that a test of higher specificity (eg, the ACTH stimulation test) should be used to confirm the diagnosis of canine hyperadrenocorticism when the CCR is above 60 x 10(-6).

Non-bacterial thrombotic endocarditis (NBTE) and, in particular, infective endocarditis (IE), are serious and potentially life-threatening diseases. An increasingly important agent of human IE is Staphylococcus aureus, which typically causes an acute endocarditis with high mortality. The study aim was to evaluate the pig as a model for non-bacterial as well as S. aureus-associated endocarditis, as these models would have several advantages compared to other laboratory animal models.Fourteen animals underwent surgery with placement of a plastic catheter in the left side of the heart. Six of the pigs did not receive a bacterial inoculation and were used to study the development of NBTE. The remaining eight pigs were inoculated intravenously once or twice with S. aureus, 10(5)-10(7) cfu/kg body weight. Two bacterial strains were used: S54F9 (porcine) and NCTC8325-4 (human). Clinical examination, echocardiography and bacterial blood cultures were used to diagnose and monitor the development of endocarditis. Animals were euthanized at between two and 15 days after catheter placement, and tissue samples were collected for bacteriology and histopathology.Pigs inoculated with 10(7) cfu/kg of S. aureus strain S54F9 developed clinical, echocardiographic and pathologic signs of IE. All other pigs, except one, developed NBTE. Serial blood cultures withdrawn after inoculation were positive in animals with IE, and negative in all other animals.S. aureus endocarditis was successfully induced in pigs with an indwelling cardiac catheter after intravenous inoculation of 10(7) cfu/kg of S. aureus strain S54F9. The model simulates typical pathological, clinical and diagnostic features seen in the human disease. Furthermore, NBTE was induced in all but one of the pigs without IE. Thus, the pig model can be used in future studies of the pathogenesis, diagnosis and therapy of NBTE and S. aureus endocarditis.

Concerns over the potential impacts of enhanced global warming and climate change have led to a number of initiatives related to anthropogenic emissions of greenhouse gases, notably from the energy sector. The most significant is the UN Framework Convention on Climate Change signed in Rio in 1992. Others include the Climate Technology Initiative, announced at the FCCC Conference of the Parties in Berlin in April 1995 and endorsed by 23 OECD/IEA countries and the European Commission.

Anisostagma rotundatum gen. et sp. nov., a lignicolous marine ascomycete belonging to the Halosphaeriaceae is described from a harbour environment at the Oresund coast, Denmark. It was found in the tidal water region of mooring posts of oak (Quercus sp.). The species is compared with Thalassogena sphaerica, Iwilsoniella rotunda and Hapsidascus hadrus.

Fresh collections of Ceriosporopsis sundica enabled an ultrastructural study of ascospores and spore appendage ontogeny. Ascospores are surrounded by an exosporic mucilaginous sheath of variable morphology, initially "slug-shaped" but at maturity ovoid. The fibrous component of the appendage is contiguous with the mesosporium through discontinuities in the episporium. Polar appendages are extensions of the sheath and not discrete mesosporial outgrowths as characteristic of Ceriosporopsis spp. A reexamination of the type material of C. cambrensis shows that spore measurements differ from those given by an earlier researcher, as does the general morphology of the appendages. It is concluded that two species are involved and C. cambrensis must be regarded a nomen dubium. Key words: appendages, Ceriosporopsis, Halosphaeriaceae, Limacospora, taxonomy, ultrastructure.

The left atrium (LA) of the heart is a validated marker of clinical and subclinical cardiovascular disease. Since the LA is a three-dimensional structure, volume-based methods of chamber quantification might be more accurate than linear methods. The aims of this study were to establish the feasibility and reproducibility of biplane two-dimensional echocardiographic LA volume measurements and to provide reference ranges for LA volume and phasic function in adult dogs (n=237) without cardiovascular disease. The study also assessed the effects of bodyweight (BW), breed, sex, age and heart rate (HR) on LA volume and function. The biplane area-length method was used to calculate LA volumes from the left apical four- and two-chamber views. LA volume and function were correlated with body size and there were significant breed differences. For dogs of all sizes and breeds, LA maximal volume had a 95th percentile of 0.92 mL/kg. There was no correlation between age or sex and LA volume or LA reservoir function, but conduit function decreased and booster pump function increased with age. LA volume and function varied with HR. LA size was calculated using the biplane area-length method, with good reproducibility and little inter-observer variability. The reference ranges presented for LA volume and function in healthy dogs could be used to refine the diagnostic criteria for the assessment of LA enlargement and altered function by conventional echocardiography.

Yorkshire terriers may be prone to respiratory disease; however, limited epidemiological information is available. A cross-sectional study design was used to compare the prevalence of respiratory signs in Yorkshire terriers with the prevalence in a population of dogs in general and to identify risk factors for respiratory clinical signs within the Swedish population of Yorkshire terriers. Data on clinical signs and risk factors were obtained from a questionnaire. The prevalence of respiratory signs in general (RS) was significantly higher among Yorkshire terriers compared with control dogs (RS 56.3 per cent and 23.0 per cent), and likewise more frequent respiratory signs (FRS) (26.0 per cent and 5.0 per cent). Age, sex and breed were shown to be significant risk factors, and an interaction between age and sex was discovered. The study indicated a sex ratio reversal in the prevalence of RS – the probability of females having RS increased with advancing age, while the probability for males was fairly constant.

Angiostrongylus vasorum has been recognised as a cause of respiratory and circulatory distress among dogs in southwestern France for more than a decade, and the nematode now appears to be of increasing importance in the British Isles and Denmark. The aim of this review is to give a concise account of present knowledge of this intriguing parasitosis.

A gall-inducing mycoparasite, Nodulisporium cecidiogenes, which was found growing in association with living Coniophora puteana is described. In the presence of N. cecidiogenes, mycelial growth of C. puteana was reduced and colony colour and aerial mycelium were modified. Gall dry weight was found to be positively correlated with the amount of available C. puteana mycelium. From host range studies with other wood decay fungi, Nodulisporium cecidiogenes seems host specific at the species level. N. cecidiogenes can be characterized as a biotrophic species with parallels to the gall forming rust fungi.

The rectal temperature is frequently measured in the morning on a daily basis in hospitalized dogs. Besides comparing the measured temperature to a population-based reference interval, it may also be of interest to evaluate the differences between consecutive measurements in order to follow the health status of a particular dog. In veterinary clinical chemistry, a parameter referred to as the critical difference, which can be used to judge if the difference between two consecutive measurements may be safely ascribed to random variation or not, has recently been introduced. The purpose of the present study was to obtain an estimate of the critical difference of the rectal temperature based on measurements of the rectal temperature in clinically healthy dogs in a hospital environment. The rectal temperature was measured in a standardized manner on 6 different days in 7 dogs. The total variance was estimated as 0.1015. The inter-individual variance was 0.0428, and the intra-analytical variance including the analytical variance was 0.0587. From these components of variance, the critical difference was calculated as 0.69 degrees C. Thus, the rectal temperature measured in the morning in hospitalized dogs can be expected to fluctuate about 0.7 degrees C from day to day due to random variation alone.

The study was performed to investigate the difference in the concentration of several haematological and clinical chemical blood components in blood obtained from the cephalic and external jugular veins in 23 dogs. A total of 17 laboratory tests were analysed and, except for two clinical chemical blood components, there was no decisive difference in the test results obtained in blood samples collected from the cephalic and external jugular vein in dogs. For creatinine and potassium, however, there was a significant difference in the test results between the two veins, the highest results in general being measured in jugular venous blood. These findings indicate that it may be advisable to establish standardised procedures when collecting blood samples and make adjustments for the difference in test results when interpreting them.

This case report describes the clinical, imaging, clinical pathology and necropsy findings in a five-year-old male Border collie with low output cardiac failure. The heart was enlarged by infiltrative lymphosarcoma.