Visualization of co-localization in Aß42-administered neuroblastoma cells reveals lysosome damage and autophagosome accumulation related to cell death.

Aß42 [amyloid-ß peptide-(1-42)] plays a central role in Alzheimer's disease and is known to have a detrimental effect on neuronal cell function and survival when assembled into an oligomeric form. In the present study we show that administration of freshly prepared Aß42 oligomers to a neuroblastoma (SH-SY5Y) cell line results in a reduction in survival, and that Aß42 enters the cells prior to cell death. Immunoconfocal and immunogold electron microscopy reveal the path of the Aß42 with time through the endosomal system and shows that it accumulates in lysosomes. A 24 h incubation with Aß results in cells that have damaged lysosomes showing signs of enzyme leakage, accumulate autophagic vacuoles and exhibit severely disrupted nuclei. Endogenous Aß is evident in the cells and the results of the present study suggest that the addition of Aß oligomers disrupts a crucial balance in Aß conformation and concentration inside neuronal cells, resulting in catastrophic effects on cellular function and, ultimately, in cell death.

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

BACKGROUND: 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. RESULTS: Annual birth proportion for Border Terriers showed a decreasing trend from 1.46% in 2005 to 0.78% in 2014. The median adult bodyweight for males (10.9 kg, IQR: 9.6-12.3, range: 6.3-25.0) was higher than for females (9.1 kg, IQR: 8.2-10.3, range: 5.2-21.6) (P < 0.001). The median longevity was 12.7 years (IQR 9.3-14.3, range 1.0-17.5).The most prevalent fine-level disorders recorded were periodontal disease (17.63%, 95% CI: 15.62-19.79), overweight/obesity (7.01%, 95% CI: 5.69-8.52) and otitis externa (6.71%, 95% CI: 5.42-8.19). The most prevalent grouped-level precision disorders were dental disorder (18.54%, 95% CI: 16.48-20.74), enteropathy (11.68%, 95% CI: 10.00-13.53), and skin disorder (10.17%, 95% CI: 8.60-11.93).Syndromic analysis showed that the most prevalent body locations affected were the head-and-neck (37.75%, 95% CI: 35.14-40.43), abdomen (18.61%, 95% CI: 16.55-20.81) and limb (11.53%, 95% CI: 9.86-13.37). At least one organ system was affected in 834 (62.85%) Border Terriers. The most prevalent organ systems affected were the digestive (32.03%, 95% CI: 29.52-34.61), integument (26.68%, 95% CI: 24.31-29.14), connective/soft tissue (11.15%, 95% CI: 9.51-12.97) and auditory (9.87%, 95% CI: 8.32-11.60). At least one affected pathophysiological process was described in 881 (66.39%) Border Terriers. The most prevalent pathophysiologic processes recorded were inflammation (31.65%, 95% CI: 29.15-34.23), nutritional (9.04%, 95% CI: 7.55-10.72), mass/swelling (8.89%, 95% CI: 7.42-10.55), traumatic (7.99%, 95% CI: 6.59-9.58) and infectious (7.76%, 95% CI: 6.38-9.33). CONCLUSIONS: This study documented a trend towards reducing ownership and relatively long-livedness in the Border Terrier. The most common disorders were periodontal disease, overweight/obesity and otitis externa. Predisposition to dental and neurological disease was suggested. These results can provide a comprehensive evidence resource to support breed-based health plans that can contribute positively to reforms to improve health and welfare within the breed.

Demography and health of Pugs under primary veterinary care in England.

BACKGROUND: The Pug is an ancient dog breed and was the fifth most commonly registered UK pedigree breed in 2014. However, the breed has been reported to be predisposed to several disorders including ocular, respiratory and dermatological problems. The VetCompass Programme collates de-identified clinical data from primary-care veterinary practices in the UK for epidemiological research. Using VetCompass clinical data, this study aimed to characterise the demography and common disorders of the general population of Pugs under veterinary care in England. RESULTS: Pugs comprised 2709 (1.03 %) of 264,260 study dogs under veterinary care from September 1(st), 2009 to 30(th) April, 2015. Annual proportional birth rates showed that Pugs rose from less than 1 % of annual birth cohorts before 2008 to comprise 2.8 % of the 2013 annual birth cohort. The most common colours of Pugs were fawn (63.1 %), black (27.7 %), apricot (7.6 %) and silver (2.1 %). Of the 1009 pugs under veterinary care in the study during 2013, 688 (68.19 %) had at least one disorder recorded. The most prevalent disorders recorded overall were overweight/obesity (number of events: 133, prevalence: 13.18 %, 95 % CI: 11.12-15.43), corneal disorder (88, 8.72 %, 95 % CI: 7.05-10.63) and otitis externa (76, 7.53 %, 95 % CI: 5.98-9.34). The most prevalent disorder groups were ophthalmological (n = 164, prevalence: 16.25 %, 95 % CI: 14.03-18.68), dermatological (157, 15.60 %, 95 % CI: 13.38-17.95) and aural (152, 15.06 %, 95 % CI: 12.91-17.42). The most prevalent body locations affected were the head-and-neck (n = 439, prevalence = 43.51 %, 95 % CI: 40.42-46.63) and abdomen (195, 19.33 %, 95 % CI: 16.93-21.90). The most prevalent organ systems affected were the integument (321, 31.81 %, 95 % CI: 28.15-35.72) and digestive (257, 25.47 %, 95 % CI: 22.54-28.65). The most prevalent pathophysiologic processes recorded were inflammation (386, 38.26 %, 95 % CI: 34.39-42.27) and congenital/developmental (153, 15.16 %, 95 % CI: 12.61-18.13). CONCLUSIONS: Ownership of Pugs in England is rising steeply. Overweight/obesity, corneal disorder and otitis externa are the most common disorders in Pugs. Identification of health priorities based on VetComapss data can support evidence-based reforms to improve health and welfare within the breed.