Border Terriers under primary veterinary care in England: demography and disorders

The Border Terrier is a working terrier type that is generally considered to be a relatively healthy and hardy breed. This study aimed to characterise the demography and common disorders of Border Terriers receiving veterinary care in England using de-identified electronic patient record data within the VetCompass™ Programme

Using the Prevalence of Individual Species of Intestinal Nematode Worms to Estimate the Combined Prevalence of Any Species

Mixed infections with roundworm, whipworm and hookworm are common, but survey reports often give only the separate prevalence of each type. However, the combined prevalence is important to estimate accurately the number of individuals who would benefit from control programmes and to make decisions about the frequency of treatment. Previous work suggests that mixed infections involving hookworm occur randomly, but that roundworm and whipworm infections are found together more frequently than would be expected by chance. We used 63 data sets from community surveys that reported both the proportions infected with individual types of worms and the combined proportion infected with any worm. We then calculated the proportion that would be infected with any type of worm if infections had occurred randomly and compared it with the observed combined proportion infected. We found a strong correlation between the observed and predicted combined proportions infected. A small downward correction of the predicted proportion infected by dividing by a factor of 1.06 brought it to a value that nearly equalled the observed proportion infected almost all the time. This simple model could be applied to published survey data to estimate accurately the number of individuals that would benefit from mass deworming

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

Trends in popularity of some morphological traits of purebred dogs in Australia.

Background The morphology of dogs can provide information about their predisposition to some disorders. For example, larger breeds are predisposed to hip dysplasia and many neoplastic diseases. Therefore, longitudinal trends in popularity of dog morphology can reveal potential disease pervasiveness in the future. There have been reports on the popularity of particular breeds and behavioural traits but trends in the morphological traits of preferred breeds have not been studied. Methods This study investigated trends in the height, dog size and head shape (cephalic index) of Australian purebred dogs. One hundred eighty-one breeds derived from Australian National Kennel Council (ANKC) registration statistics from 1986 to 2013 were analysed. Weighted regression analyses were conducted to examine trends in the traits by using them as outcome variables, with year as the explanatory variable and numbers of registered dogs as weights. Linear regression investigated dog height and cephalic index (skull width/skull length), and multinomial logistic regression studied dog size. Results The total number of ANKC registration had decreased gradually from 95,792 in 1986 to 66,902 in 2013. Both weighted minimal height (p = 0.014) and weighted maximal height (p < 0.001) decreased significantly over time, and the weighted cephalic index increased significantly (p < 0.001). The odds of registration of medium and small breeds increased by 5.3 % and 4.2 %, respectively, relative to large breeds (p < 0.001) and by 12.1 % and 11.0 %, respectively, relative to giant breeds (p < 0.001) for each 5-year block of time. Conclusions Compared to taller and larger breeds, shorter and smaller breeds have become relatively popular over time. Mean cephalic index has increased, which indicates that Australians have gradually favoured breeds with shorter and wider heads (brachycephalic). These significant trends indicate that the dog morphological traits reported here may potentially influence how people select companion dogs in Australia and provide valuable predictive information on the pervasiveness of diseases in dogs. Keywords: Purebred dogs, Dog popularity, Dog height, Dog size, Cephalic index, Brachycephalic Disease, predisposition, Australia. Plain English Summary Some diseases in dogs are related to certain physical characteristics. For example, larger breeds have a higher risk of getting hip dysplasia and certain neoplastic diseases while breeds with wider and shorter heads, such as Pug and French bulldog, are more likely to experience breathing problems and dystocia. Therefore, if we know the trends in popularity of dogs of a certain morphology, we may be able to predict disease pervasiveness. The study aimed to investigate the trends in the height, dog size and head shape of Australian purebred dogs. The numbers of dogs registered within the 181 breeds in Australian National Kennel Council (ANKC) every year from 1986 to 2013 were obtained and analysed. The total number of ANKC registration had decreased from 95,792 in 1986 to 66,902 in 2013. Compared to taller and larger breeds, shorter and smaller breeds have become relatively popular over time. Also, the data suggest that Australians increasingly favour dogs with shorter and wider heads for whose welfare veterinarians often express concern [1, 2]. The results indicate that dog height, dog size and dog head shape may potentially influence how people select companion dogs in Australia and provide valuable predictive information on trends in disease prevalence, enabling the veterinary profession and industry to prepare for potential future caseloads

Prevalence and Factors Associated with Intestinal Parasitic Infection among Children in an Urban Slum of Karachi

Background:Intestinal parasitic infections are endemic worldwide and have been described as constituting the greatest single worldwide cause of illness and disease. Poverty, illiteracy, poor hygiene, lack of access to potable water and hot and humid tropical climate are the factors associated with intestinal parasitic infections. The study aimed to estimate prevalence and identify factors associated with intestinal parasitic infections among 1 to 5 years old children residing in an urban slum of Karachi Pakistan. Methods And PrincipalFindings:A cross sectional survey was conducted from February to June 2006 in Ghosia Colony Gulshan Town Karachi, Pakistan. A simple random sample of 350 children aged 1-5 years was collected. The study used structured pre-tested questionnaire, anthropometric tools and stool tests to obtain epidemiological and disease data. Data were analyzed using appropriate descriptive, univariate and multivariable logistic regression methods. The mean age of participants was 2.8 years and 53% were male. The proportions of wasted, stunted and underweight children were 10.4%, 58.9% and 32.7% respectively. The prevalence of Intestinal parasitic infections was estimated to be 52.8% (95% CI: 46.1, 59.4). Giardia lamblia was the most common parasite followed by Ascaris lumbricoides, Blastocystis hominis and Hymenolepis nana. About 43% children were infected with single parasite and 10% with multiple parasites. Age {Adjusted Odds Ratio (aOR) = 1.5, 95% CI: 1.1, 1.9}, living in rented households (aOR = 2.0, 95% CI: 1.0, 3.9) and history of excessive crying (aOR = 1.9, 95% CI: 1.0, 3.4) were significantly associated with intestinal parasitic infections.Conclusion:Intestinal parasites are highly prevalent in this setting and poverty was implicated as an important risk factor for infection. Effective poverty reduction programmes and promotion of deworming could reduce intestinal parasite carriage. There is a need for mass scale campaigns to create awareness about health and hygiene

Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed

The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression profiling in a naturally occurring endothelial sarcoma of dogs (hemangiosarcoma). Naturally occurring hemangiosarcomas of Golden Retrievers clustered separately from those of non-Golden Retrievers, with contributions from transcription factors, survival factors, and from pro-inflammatory and angiogenic genes, and which were exclusively present in hemangiosarcoma and not in other tumors or normal cells (i.e., they were not due simply to variation in these genes among breeds). Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) was among genes preferentially enriched within known pathways derived from gene set enrichment analysis when characterizing tumors from Golden Retrievers versus other breeds. Heightened VEGFR1 expression in these tumors also was apparent at the protein level and targeted inhibition of VEGFR1 increased proliferation of hemangiosarcoma cells derived from tumors of Golden Retrievers, but not from other breeds. Our results suggest heritable factors mold gene expression phenotypes, and consequently biological behavior in sporadic, naturally occurring tumors

Cyclooxygenase-2 overexpression is common in serrated and non-serrated colorectal adenoma, but uncommon in hyperplastic polyp and sessile serrated polyp/adenoma

<p>Abstract</p> <p>Background</p> <p>Cyclooxygenase-2 (COX-2, <it>PTGS2</it>) plays an important role in colorectal carcinogenesis. COX-2 overexpression in colorectal cancer is inversely associated with microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). Evidence suggests that MSI/CIMP+ colorectal cancer may arise through the serrated tumorigenic pathway through various forms of serrated neoplasias. Therefore, we hypothesized that COX-2 may play a less important role in the serrated pathway.</p> <p>Methods</p> <p>By immunohistochemistry, we assessed COX-2 expression in 24 hyperplastic polyps, 7 sessile serrated polyp/adenomas (SSA), 5 mixed polyps with SSA and adenoma, 27 traditional serrated adenomas, 515 non-serrated adenomas (tubular adenoma, tubulovillous adenoma and villous adenoma), 33 adenomas with intramucosal carcinomas, 96 adenocarcinomas with serration (corkscrew gland) and 111 adenocarcinomas without serration.</p> <p>Results</p> <p>Strong (2+) COX-2 overexpression was more common in non-serrated adenomas (28% = 143/515) than in hyperplastic polyps (4.2% = 1/24, p = 0.008) and serrated polyps (7 SSAs and 5 mixed polyps) (0% = 0/12, p = 0.04). Furthermore, any (1+/2+) COX-2 overexpression was more frequent in non-serrated adenomas (60% = 307/515) than in hyperplastic polyps (13% = 3/24, p < 0.0001) and serrated polyps (SSAs and mixed polyps) (25% = 3/12, p = 0.03). Traditional serrated adenomas and non-serrated adenomas showed similar frequencies of COX-2 overexpression. Regardless of serration, COX-2 overexpression was frequent (~85%) in colorectal adenocarcinomas. Tumor location was not significantly correlated with COX-2 overexpression, although there was a trend towards higher frequencies of COX-2 overexpression in distal tumors (than proximal tumors) among hyperplastic polyps, SSAs, mixed polyps, traditional serrated adenomas and adenocarcinomas.</p> <p>Conclusion</p> <p>COX-2 overexpression is infrequent in hyperplastic polyp, SSA and mixed polyp with SSA and adenoma, compared to non-serrated and serrated adenoma. COX-2 overexpression becomes more frequent as tumors progress to higher grade neoplasias. Our observations suggest that COX-2 may play a less significant role in the serrated pathway of tumorigenesis; however, COX-2 may still play a role in later stage of the serrated pathway.</p