Assessment of the inter-rater agreement of corneal cytology and culture findings in canine ulcerative keratitis.

OBJECTIVES: To assess the inter-rater agreement of corneal cytology findings in canine ulcerative keratitis by veterinary surgeons of different training levels and the agreement of corneal cytology with culture. MATERIALS AND METHODS: Dogs with progressive ulcerative keratitis were prospectively recruited for corneal cytology and culture. Corneal cytology slides were reviewed by veterinary surgeons of different training levels (three general practitioners, three ophthalmologists and three pathologists). The inter-rater agreement of cytology findings and agreement of cytology with culture was assessed using the kappa measure of agreement. RESULTS: The study included 145 corneal cytology samples from 143 dogs (145 eyes) with progressive ulcerative keratitis. Positive cultures were obtained from 81 of 145 (56%) eyes. The most commonly isolated pathogens were Streptococcus canis, Pseudomonas aeruginosa and Staphylococcus pseudintermedius. The results demonstrated increased inter-rater agreement of corneal cytology and increased agreement with culture with increased ocular pathology expertise (pathologists > ophthalmologists > general practitioners). CLINICAL SIGNIFICANCE: This study provides important information about the diagnostic value of corneal cytology in canine ulcerative keratitis and the most common pathogens involved in such cases in the UK. Based on the results of this study, cytology findings should be interpreted in conjunction with the expertise of the observer. For maximal pathogen identification, both cytology and culture should be considered.

Prospective randomised blinded clinical trial assessing effectiveness of three dental plaque control methods in dogs.

OBJECTIVES: To assess the effectiveness of three commonly used methods of controlling dental plaque accumulation within a general practice setting. MATERIALS AND METHODS: A blinded study, block randomising dogs at recruitment to receive one of three treatments to start after a routine scale and polish procedure: once daily tooth brushing using a toothbrush and veterinary toothpaste, once daily administration of a single dental hygiene chew or a prescription dental diet. Blinded scoring of plaque accumulation, both coverage and thickness, was performed at the end of the 6-week study. RESULTS: A total of 22 dogs completed the study, which simultaneously assessed the effectiveness of the three means of plaque control. Daily tooth brushing was shown to be more than three times as effective at controlling plaque accumulation compared to using a daily dental chew or dental diet. The dental plaque scores for the diet and dental chews were not significantly different from one another and there was much greater variability in the mouth scores for these two groups of dogs compared to the tooth brushing group. CLINICAL SIGNIFICANCE: The study design has been shown to be an effective means of assessing plaque accumulation over a 6-week period using a clean mouth model. Secondly, this study adds to the evidence which shows that daily tooth brushing is the most effective single method of reducing plaque accumulation and optimising dogs' oral health.

Research priorities for conservation and natural resource management in Oceania's small-island developing states.

For conservation science to effectively inform management, research must focus on creating the scientific knowledge required to solve conservation problems. We identified research questions that, if answered, would increase the effectiveness of conservation and natural resource management practice and policy in Oceania's small-island developing states. We asked conservation professionals from academia, governmental, and nongovernmental organizations across the region to propose such questions and then identify which were of high priority in an online survey. We compared the high-priority questions with research questions identified globally and for other regions. Of 270 questions proposed by respondents, 38 were considered high priority, including: What are the highest priority areas for conservation in the face of increasing resource demand and climate change? How should marine protected areas be networked to account for connectivity and climate change? What are the most effective fisheries management policies that contribute to sustainable coral reef fisheries? High-priority questions related to the particular challenges of undertaking conservation on small-island developing states and the need for a research agenda that is responsive to the sociocultural context of Oceania. Research priorities for Oceania relative to elsewhere were broadly similar but differed in specific issues relevant to particular conservation contexts. These differences emphasize the importance of involving local practitioners in the identification of research priorities. Priorities were reasonably well aligned among sectoral groups. Only a few questions were widely considered answered, which may indicate a smaller-than-expected knowledge-action gap. We believe these questions can be used to strengthen research collaborations between scientists and practitioners working to further conservation and natural resource management in this region.

Stress in new graduates: can the profession do more to help?

Richard Halliwell and colleagues believe that it can, on the basis of a survey they conducted to assess the incidence of poor mental health and wellbeing in recent veterinary graduates, and workplace factors that might be associated with this.

Whole-Body Barometric Plethysmography Characterizes Upper Airway Obstruction in 3 Brachycephalic Breeds of Dogs.

BACKGROUND: A novel test using whole-body barometric plethysmography (WBBP) was developed recently to diagnose brachycephalic obstructive airway syndrome (BOAS) in unsedated French bulldogs. HYPOTHESIS/OBJECTIVES: The hypotheses of this study were: (1) respiratory characteristics are different between healthy nonbrachycephalic dogs and brachycephalic dogs; and among pugs, French bulldogs, and bulldogs; and (2) obesity and stenotic nares are risk factors for BOAS. The main objective was to establish a diagnostic test for BOAS in these 3 breeds. ANIMALS: A total of 266 brachycephalic dogs (100 pugs, 100 French bulldogs, and 66 bulldogs) and 28 nonbrachycephalic dogs. METHODS: Prospective study. Exercise tolerance tests with respiratory functional grading, and WBBP were performed on all dogs. Data from WBBP were associated with functional grades to train quadratic discriminant analysis tools to assign dogs to BOAS+ and BOAS- groups. A BOAS index (0-100%) was calculated for each dog. Receiver operating characteristic (ROC) curves were used to evaluate classification ability. RESULTS: Minute volume was decreased significantly in asymptomatic pugs (P = .009), French bulldogs (P = .026), and bulldogs (P < .0001) when compared to nonbrachycephalic controls. Respiratory characteristics were different among breeds and affected dogs had a significant increase in trace variation. The BOAS index predicted BOAS status for each breed with 94-97% (95% confidence interval [CI], 88.9-100%) accuracy (area under the ROC curve). Both obesity (P = .04) and stenotic nares (P = .004) were significantly associated with BOAS. CONCLUSIONS AND CLINICAL IMPORTANCE: The WBBP can be used as a clinical tool to diagnose BOAS noninvasively and objectively.

Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity.

BACKGROUND: The term 'metabolically healthy obese (MHO)' is distinguished using body mass index (BMI), yet BMI is a poor index of adiposity. Some epidemiological data suggest that MHO carries a lower risk of cardiovascular disease (CVD) or mortality than being normal weight yet metabolically unhealthy. OBJECTIVES: We aimed to undertake a detailed phenotyping of individuals with MHO by using imaging techniques to examine ectopic fat (visceral and liver fat deposition) and myocardial function. We hypothesised that metabolically unhealthy individuals (irrespective of BMI) would have adverse levels of ectopic fat and myocardial dysfunction compared with MHO individuals. SUBJECTS: Individuals were categorised as non-obese or obese (BMI ⩾30 kg m(-2)) and as metabolically healthy or unhealthy according to the presence or absence of metabolic syndrome. METHODS: Sixty-seven individuals (mean±s.d.: age 49±11 years) underwent measurement of (i) visceral, subcutaneous and liver fat using magnetic resonance imaging and proton magnetic resonance spectroscopy, (ii) components of metabolic syndrome, (iii) cardiorespiratory fitness and (iv) indices of systolic and diastolic function using tissue Doppler echocardiography. RESULTS: Cardiorespiratory fitness was similar between all groups; abdominal and visceral fat was highest in the obese groups. Compared with age- and BMI-matched metabolically healthy counterparts, the unhealthy (lean or obese) individuals had higher liver fat and decreased early diastolic strain rate, early diastolic tissue velocity and systolic strain indicative of subclinical systolic and diastolic dysfunction. The magnitude of dysfunction correlated with the number of components of metabolic syndrome but not with BMI or with the degree of ectopic (visceral or liver) fat deposition. CONCLUSIONS: Myocardial dysfunction appears to be related to poor metabolic health rather than simply BMI or fat mass. These data may partly explain the epidemiological evidence on CVD risk relating to the different obesity phenotypes.

Toxic and transcriptional responses of PC12 cells to soluble tungsten alloy surrogates.

There is increasing evidence that metals have a role in the etiology of diverse neurological diseases. This study used PC12 cells as an in vitro model to examine the toxicity of tungsten alloys that have important military applications. Initially, the relative concentrations of tungsten (W), nickel (Ni), and cobalt (Co) mobilized from pellets of a weapons-grade tungsten alloy incubated in physiologically relevant solutions were determined. Dosing solutions of soluble metal salts that were equivalent in ratio to those mobilized from these alloy pellets were used to treat nerve growth factor (NGF) differentiated PC12 cells. Treatments consisted of single (W, Ni or Co), paired (W/Ni, W/Co or Ni/Co) or complete (W/Ni/Co) metal exposures for 24 h followed by measurement of cytotoxicity, viability, and microarray analysis to examine their impact on survival and viability, global gene expression, and biological processes. Gene expression changed dramatically with addition of NGF. Addition of Ni or Co either singly or in combination further impacted gene expression. An observed additive effect of Ni and Co on gene expression was unaffected by the addition of W. The work showed that tungsten, as found in this tungsten alloy, had minimal relative toxicity as compared to the other alloy components when used either alone or in combination.

Comparative neuropathology of ovine enterotoxemia produced by Clostridium perfringens type D wild-type strain CN1020 and its genetically modified derivatives.

Clostridium perfringens type D causes enterotoxemia in sheep and goats. The disease is mediated by epsilon toxin (ETX), which affects the cerebrovascular endothelium, increasing vascular permeability and leading to cerebral edema. In the present study, we compared the distribution and severity of the cerebrovascular changes induced in lambs by C. perfringens type D strain CN1020, its isogenic etx null mutant, and the ETX-producing complemented mutant. We also applied histochemical and immunohistochemical markers to further characterize the brain lesions induced by ETX. Both ETX-producing strains induced extensive cerebrovascular damage that did not differ significantly between each other in nature, neuroanatomic distribution, or severity. By contrast, lambs inoculated with the etx mutant or sterile, nontoxic culture medium did not develop detectable brain lesions, confirming that the neuropathologic effects observed in these infections are dependent on ETX production. Lambs treated with the wild-type and complemented strains showed perivascular and mural vascular edema, as well as serum albumin extravasation, particularly severe in the cerebral white matter, midbrain, medulla oblongata, and cerebellum. Brains of animals inoculated with the ETX-producing strains showed decreased expression of glial fibrillary acidic protein and increased expression of aquaporin-4 in the end-feet processes of the astrocytes around blood vessels. Early axonal injury was demonstrated with anti-amyloid precursor protein immunohistochemistry. Perivascular accumulation of macrophages/microglia with intracytoplasmic albumin globules was also observed in these animals. This study demonstrates that ETX is responsible for the major cerebrovascular changes in C. perfringens type D-induced disease.

Characterizing spatial uncertainty when integrating social data in conservation planning.

Recent conservation planning studies have presented approaches for integrating spatially referenced social (SRS) data with a view to improving the feasibility of conservation action. We reviewed the growing conservation literature on SRS data, focusing on elicited or stated preferences derived through social survey methods such as choice experiments and public participation geographic information systems. Elicited SRS data includes the spatial distribution of willingness to sell, willingness to pay, willingness to act, and assessments of social and cultural values. We developed a typology for assessing elicited SRS data uncertainty which describes how social survey uncertainty propagates when projected spatially and the importance of accounting for spatial uncertainty such as scale effects and data quality. These uncertainties will propagate when elicited SRS data is integrated with biophysical data for conservation planning and may have important consequences for assessing the feasibility of conservation actions. To explore this issue further, we conducted a systematic review of the elicited SRS data literature. We found that social survey uncertainty was commonly tested for, but that these uncertainties were ignored when projected spatially. Based on these results we developed a framework which will help researchers and practitioners estimate social survey uncertainty and use these quantitative estimates to systematically address uncertainty within an analysis. This is important when using SRS data in conservation applications because decisions need to be made irrespective of data quality and well characterized uncertainty can be incorporated into decision theoretic approaches.

[High fat diet-induced molecular and physiological dysfunction of the urinary bladder]. / Hochfettdiät induziert molekulare und physiologische Dysfunktionen der Harnblase.

BACKGROUND: Obesity with its multiple comorbidities has become a global pandemia. We here report on the pathophysiological aspects of obesity-associated urinary bladder dysfunctions. MATERIAL AND METHODS: Our results are based on multiple in vitro and in vivo studies including a high fat diet (HFD) rat animal model of which the details are given in the cited publications. RESULTS: In cultured human detrusor muscle cells, obesity-related pathophysiological mechanisms were directly induced by the saturated free fatty acid palmitate. In HFD animals, we found serious fibrosis of the bladder wall and downregulation of the muscarinic M3-receptor leading to diminished contractility of the urinary bladder. Bariatric surgical intervention (sleeve gastrectomy) reversed the fibrosis. CONCLUSION: Our results support the relevance of obesity for urological bladder dysfunction. The epidemic dimension of obesity with its steadily growing number of cases requires a re-evaluation of this pathological condition in the urological context.

On fragmenting, densely mineralised acellular protrusions into articular cartilage and their possible role in osteoarthritis.

High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first described in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. We now report them in human material. Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were imaged using magnetic resonance imaging (MRI) dual echo steady state at 0.23 mm resolution, then 26-µm resolution high contrast X-ray microtomography, sectioned and embedded in polymethylmethacrylate, blocks cut and polished and re-imaged with 6-µm resolution X-ray microtomography. Tissue mineralisation density was imaged using backscattered electron SEM (BSE SEM) at 20 kV with uncoated samples. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. HDMP arise via the extrusion of an unknown mineralisable matrix into clefts in HAC, a process of acellular dystrophic calcification. Their formation may be an extension of a crack self-healing mechanism found in bone and articular calcified cartilage. Mineral concentration exceeds that of articular calcified cartilage and is not uniform. It is probable that they have not been reported previously because they are removed by decalcification with standard protocols. Mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. HDMP are surrounded by HAC, are brittle, and show fault lines within them. Dense fragments found within damaged HAC could make a significant contribution to joint destruction. At least larger HDMP can be detected with the best MRI imaging ex vivo.

Growth differentiation factor-15 in Takotsubo cardiomyopathy: diagnostic and prognostic value.

BACKGROUND: Growth differentiation factor-15 (GDF-15), a stress responsive cytokine, has emerged as a marker of adverse outcome in various cardiovascular diseases. Since GDF-15 has not been evaluated in patients with Takotsubo cardiomyopathy (TTC), the present study sought to investigate the diagnostic and prognostic value in this patient cohort. METHODS: A total of 22 patients presenting with TTC were matched for age and gender with 22 ST-segment elevation myocardial infarction (STEMI) patients. GDF-15 concentrations were measured at admission and 1 day thereafter. The primary clinical endpoint of the TTC cohort was the composite of death, cardiogenic shock, or new congestive heart failure within 6 months. RESULTS: TTC patients showed significantly higher GDF-15 values on admission compared to patients presenting with STEMI (median 3047 ng/l [interquartile range 2256-7572] versus median 1527 ng/l [interquartile range 1152-2677]; p=0.002). TTC patients with a biventricular ballooning pattern and patients experiencing major adverse cardiac events during the first 6 months after acute presentation showed significantly higher GDF-15 concentrations on admission (p=0.008 and p=0.005, respectively). Biventricular ballooning was identified as a predictor for elevated GDF-15 values on admission (p=0.03). High GDF-15 levels on admission were the only significant predictor for the combined clinical endpoint in multivariable regression analysis (p=0.02). CONCLUSION: TTC patients showed markedly high, but transient elevation of GDF-15 levels. Biventricular ballooning was associated with particularly high GDF-15 concentrations. Elevated GDF-15 values on admission were a strong predictor of adverse clinical outcome.

A cross-sectional study of mental health in UK veterinary undergraduates.

Wellbeing (positive mental health) and mental ill-health of veterinary students from a single UK school were quantified using validated psychological scales. Attitudes towards mental ill-health and suicide were also assessed. Results were compared with published data from the UK general population and veterinary profession. Of the total student population (N=1068), 509 (48 per cent) completed a questionnaire. Just over half (54 per cent) of the respondents had ever experienced mental ill-health, with the majority reporting a first occurrence before veterinary school. Student wellbeing was significantly poorer (p<0.0001) than general population estimates, but not significantly different (p=0.2) from veterinary profession estimates. Degree of mental distress in students was significantly higher than in the general population (p<0.0001). Despite the majority (94 per cent) agreeing that 'Anyone can suffer from mental health problems', students were significantly more likely than members of the general population to agree that 'If I were suffering from mental health problems, I wouldn't want people knowing about it' (p<0.0001). Students were more likely to have thought about suicide, but less likely to have made an attempt (p<0.001; p=0.005), than members of the general population. The possibility of non-response bias must be considered when interpreting findings. However, strong similarities between results from this study population and the UK veterinary profession, as well as other veterinary student populations internationally, suggest no substantial school-level bias.

Epsilon toxin is essential for the virulence of Clostridium perfringens type D infection in sheep, goats, and mice.

Clostridium perfringens type D causes disease in sheep, goats, and other ruminants. Type D isolates produce, at minimum, alpha and epsilon (ETX) toxins, but some express up to five different toxins, raising questions about which toxins are necessary for the virulence of these bacteria. We evaluated the contribution of ETX to C. perfringens type D pathogenicity in an intraduodenal challenge model in sheep, goats, and mice using a virulent C. perfringens type D wild-type strain (WT), an isogenic ETX null mutant (etx mutant), and a strain where the etx mutation has been reversed (etx complemented). All sheep and goats, and most mice, challenged with the WT isolate developed acute clinical disease followed by death in most cases. Sheep developed various gross and/or histological changes that included edema of brain, lungs, and heart as well as hydropericardium. Goats developed various effects, including necrotizing colitis, pulmonary edema, and hydropericardium. No significant gross or histological abnormalities were observed in any mice infected with the WT strain. All sheep, goats, and mice challenged with the isogenic etx mutant remained clinically healthy for ≥24 h, and no gross or histological abnormalities were observed in those animals. Complementation of etx knockout restored virulence; most goats, sheep, and mice receiving this complemented mutant developed clinical and pathological changes similar to those observed in WT-infected animals. These results indicate that ETX is necessary for type D isolates to induce disease, supporting a key role for this toxin in type D disease pathogenesis.

Comparison of surgical duration of canine ovariectomy and ovariohysterectomy in a veterinary teaching hospital.

OBJECTIVE: To prospectively evaluate ovariectomy and ovariohysterectomy via midline coeliotomy when being employed by supervised final year veterinary students for the purpose of routine canine neutering. METHODS: One hundred and eight female dogs of various breeds, presented to a veterinary teaching hospital for neutering, were randomly allocated to one of two surgery groups, ovariectomy or ovariohysterectomy. The specified procedure was performed by a supervised final year veterinary student. If the duration of surgery exceeded 2 hours or if major surgical or anaesthetic complications occurred, the supervising surgeon intervened to complete the procedure. RESULTS: Data analysed included age, weight, time from first incision to start of closure, duration of closure, total surgical time and length of incision. Fifty-four dogs underwent each procedure. There was no significant difference between the two surgery groups for any of the measured variables. CLINICAL SIGNIFICANCE: Ovariectomy is not associated with shorter surgical times or smaller abdominal incisions than ovariohysterectomy when employed by inexperienced surgeons. As no major complications novel to ovariectomy occurred in this cohort of dogs, this study adds support to the existing literature indicating that ovariectomy is an acceptable alternative to ovariohysterectomy for canine neutering.

Canine idiopathic epilepsy: prevalence, risk factors and outcome associated with cluster seizures and status epilepticus.

OBJECTIVES: To evaluate the prevalence of cluster seizures and status epilepticus in dogs with idiopathic epilepsy and determine risk factors for cluster seizure frequency, severity and patient outcome. METHODS: Retrospective review of medical records of 407 dogs with idiopathic epilepsy was made. Follow-up questionnaires were evaluated in cases with cluster seizures. RESULTS: Mean age at diagnosis of idiopathic epilepsy was 4 years. Cluster seizures were documented in 169 (41%) dogs. German shepherds and boxers were significantly (P=0·04 and 0·01, respectively) more likely to suffer from cluster seizures compared to Labrador retrievers. There was no association between the occurrence of status epilepticus and cluster seizures and frequency and severity of cluster seizures and status epilepticus episodes with age or breed. Intact males were twice as likely (P=0·003) than neutered dogs to suffer from cluster seizures. Intact females had significantly (P=0·007) more frequent cluster seizures than neutered dogs. The median survival time for all dogs with cluster seizures was 95 months. Significantly (P=0·03) more dogs with frequent cluster seizures were euthanased because of the cluster seizures. CLINICAL SIGNIFICANCE: There was a high prevalence of cluster seizures in dogs with idiopathic epilepsy. Neutering status appears to influence cluster seizure occurrence with intact females more likely to experience more frequent episodes. Euthanasia is associated with frequency of cluster seizure episodes.

Feline vaccination practices and protocols used by veterinarians in the United Kingdom.

Vaccination is an important aspect of disease control in the feline population, as it prevents disease or reduces its severity in individual cats. However the types of antigens that should be administered to cats, the frequency of administration of certain antigens and the anatomical location at which vaccines should be administered are controversial. Various groups have developed guidelines to help veterinarians decide vaccine protocols for cats in their care. The aim of this study was to survey veterinarians in the United Kingdom about the vaccination protocols used in 2007-2008. A questionnaire about aspects of feline vaccination was distributed to a 431 veterinary practices taking part in a case-control study of feline injection site sarcomas. A response rate of 72% was achieved. The majority of veterinarians who responded administered the commonly used antigens annually (84-96% of practices). Most of the veterinarians administered most vaccines in the interscapular region (90-96% of practices depending on the antigen). The vaccination practices of the veterinarians were not consistent with the published vaccination guidelines at that time.