The Pathology of Equine Gastrointestinal Disease

To initiate the study a comprehensive review was made of the available literature relating to the equine gastrointestinal tract. This is presented in the literature review. It includes papers and texts concerning the anatomy and function of the equine gastrointestinal tract as well as causes of clinical disease and pathological lesions. A total of 213 horses, ponies and donkeys underwent a full post mortem examination by Glasgow University Veterinary School Department of Veterinary Pathology in the the 5 year period 1987-1991 inclusive. The majority were mixed breed pleasure animals rather than pedigree competition horses. These findings are presented in Part I, the Necropsy Series. The lesions recorded were considered, on the basis of appearance and clinical history, to be either principal or incidental and were then grouped by the system in which they were found. Lesions were identified in all anatomical systems. The gastrointestinal system was found to be by far and away the most frequently affected by both principal lesions, ie those considered to have resulted in the animal's death or humane destruction, and incidental lesions with no reported history of associated clinical disease. The Necropsy Series identified 92 animals with one or more lesions of the gastrointestinal system which were studied in more detail. These findings are presented in Part II, the Gastrointestinal Series. Here the general groupings used in the Necropsy Series were broken down by location and the actual lesion identified. In addition, other factors such as possible seasonal incidence and any concurrent, contributory lesions were also studied. Grass sickness was the most frequently identified significant primary condition and parasitism featured heavily as a cause of incidental lesions. The Gastrointestinal Series in turn revealed a group of 20 animals with clinical evidence of malabsorption and a chronic enteropathy which were studied in depth. Histopathological examination of multiple tissues from these cases allowed them to be divided into 2 groups, one of recognised conditions where a definitive diagnosis was made and one where only a morphological diagnosis was made. This series is presented in Part III, the Enteropathy Series. The recognised conditions identified by the Enteropathy Series were alimentary lymphosarcoma, equine granulomatous enteritis, equine eosinophilic enteritis, cyathostomiasis, Phenylbutazone toxicity and coccidiosis. However, these 6 conditions only accounted for 11 of the 20 animals. Eight of the remaining 9 animals had gastrointestinal lesions which differed significantly from those previously described in the equine literature. These were the animals where only a morphological diagnosis was made. The remaining case had clinical evidence of malabsorption in the form of an abnormal oral glucose tolerance test result but apparently no significant gross or microscopic lesions of the gastrointestinal tract, just extremely abnormal dentition. The Enteropathy Series revealed that the recognised equine inflammatory bowel diseases do occur in the UK and are not restricted to Standardbreds and Thoroughbreds as the available literature would suggest

Control of protein palmitoylation by regulating substrate recruitment to a zDHHC-protein acyltransferase

Although palmitoylation regulates numerous cellular processes, as yet efforts to manipulate this post-translational modification for therapeutic gain have proved unsuccessful. The Na-pump accessory sub-unit phospholemman (PLM) is palmitoylated by zDHHC5. Here, we show that PLM palmitoylation is facilitated by recruitment of the Na-pump α sub-unit to a specific site on zDHHC5 that contains a juxtamembrane amphipathic helix. Site-specific palmitoylation and GlcNAcylation of this helix increased binding between the Na-pump and zDHHC5, promoting PLM palmitoylation. In contrast, disruption of the zDHHC5-Na-pump interaction with a cell penetrating peptide reduced PLM palmitoylation. Our results suggest that by manipulating the recruitment of specific substrates to particular zDHHC-palmitoyl acyl transferases, the palmitoylation status of individual proteins can be selectively altered, thus opening the door to the development of molecular modulators of protein palmitoylation for the treatment of disease

Physical function following TKA compared to age matched healthy controls

Purpose: to explore whether physical and functional impairments exist in those who have undergone primary TKA compared to age matched healthy controls. Relevance: Many studies have suggested that although function generally improves following TKA, patients continue to experience significant functional limitations. Most of these studies however have assessed function using self-reported measures despite recommendations that both self-report and performance based measures are required to capture the full spectrum of functional ability. Furthermore, there have been no recent studies that have comprehensively compared outcomes in TKA with those who have no knee related pathology. Therefore, the evidence to suggest that functional limitations persist cannot be considered as robust. Participants: A group of patients (n = 15) were recruited who had undergone primary TKA for osteoarthritis between 10 and 14 months previously (median age = 71 years). A group of age matched health controls (n = 12, median age = 69.5 years) were recruited from local community groups. Methods: Self reported function (0-100 scale where 0 is best), timed-up-and-go, stair ascent/descent, walking speed, leg extensor power and range of motion were compared between groups. Analysis: Mann-Whitney U-tests were used to detect inter-group differences. The alpha level was set at 0.05. Results: Maximum flexion in the TKA group (median = 110o) was significantly less (p = 0.002) than the control group (median = 120o). The TKA group reported significantly worse function (median scores TKA = 10.0, control = 0.00, p = 0.028). No significant differences (p >0.05) however were found between groups in any of the performance based measures of function (timed up and go, timed stair ascent/descent, walking speed) or in knee extensor strength. Conclusions: although individuals with TKA perceived their functional ability to be significantly worse than their healthy counterparts, there was no evidence to suggest that significant functional impairments existed in this small group. Implications: expectations of outcome in TKA have been shown to be an important factor in overall patient satisfaction with their surgery. The results of this study could help to provide improved information regarding functional ability following TKA.sch_phyunpub2310unpu

Prostate cancer: Exploring the reasons for timing of presentation and diagnosis. Final Report

Executive Summary Prostate cancer is the most common malignancy in men, and the third highest cancer mortality in men. The observed increase in incidence alongside the reduction in men presenting with advanced disease is likely to be due in part to improved early detection rates associated with the introduction of the PSA test. This study was undertaken to determine the pattern of timing of presentation with a diagnosis of prostate cancer in Glasgow. A postal survey was distributed to all men in Greater Glasgow who were diagnosed with prostate cancer in 2008/9 (N=458). The survey was returned by 320 men; a response rate of 70%. A stratified sub-sample of survey respondents were interviewed (N=30); when possible, men’s partners were included in these interviews. Quantitative data were analysed with descriptive and inferential statistics (chi-square and Spearman’s). Qualitative data were analysed thematically, informed by psychosocial theories of delay

Greasing the wheels or a spanner in the works?:Regulation of the cardiac sodium pump by palmitoylation

The ubiquitous sodium/potassium ATPase (Na pump) is the most abundant primary active transporter at the cell surface of multiple cell types, including ventricular myocytes in the heart. The activity of the Na pump establishes transmembrane ion gradients that control numerous events at the cell surface, positioning it as a key regulator of the contractile and metabolic state of the myocardium. Defects in Na pump activity and regulation elevate intracellular Na in cardiac muscle, playing a causal role in the development of cardiac hypertrophy, diastolic dysfunction, arrhythmias and heart failure. Palmitoylation is the reversible conjugation of the fatty acid palmitate to specific protein cysteine residues; all subunits of the cardiac Na pump are palmitoylated. Palmitoylation of the pump’s accessory subunit phospholemman (PLM) by the cell surface palmitoyl acyl transferase DHHC5 leads to pump inhibition, possibly by altering the relationship between the pump catalytic α subunit and specifically bound membrane lipids. In this review, we discuss the functional impact of PLM palmitoylation on the cardiac Na pump and the molecular basis of recognition of PLM by its palmitoylating enzyme DHHC5, as well as effects of palmitoylation on Na pump cell surface abundance in the cardiac muscle. We also highlight the numerous unanswered questions regarding the cellular control of this fundamentally important regulatory process

Exploring researchers' views on Metrics and research impact: Internal report

Research excellence is a goal that universities and researchers alike strive for, but how do we identify and measure research excellence? Do quantitative metrics demonstrate the impact that researchers are aiming for? This report details the results of an exploratory case study investigating how researchers responded to a range of quantitative metrics. As a part of their approach, the project team interviewed thirteen academic staff at the University of Waikato across a range of disciplines. A thematic analysis of the interviews was carried out, bringing to light eight dominant themes from the participants’ discussions: • No one-size fits all - impact and excellence varies greatly across disciplines and matter more to some disciplines than others • Lack of understanding of metrics and reliance on h-index • Metrics are subjective and can be gamed • A general nervousness around metrics or disdain, especially for Altmetrics • Cultural considerations and the importance of the collective • Disconnect between what they value and what they think their peers value • Publishing decisions are driven by a diverse range of factors • Varying levels of importance in getting research out into the public including OA This paper argues that metrics can be used as a tool for researchers, but should be understood in the context of non-quantitative measures. Metrics alone cannot determine how impactful a researcher’s contribution may be. It is important for researchers to be recognised as individuals in order for them to tell the story of their work. This will require upskilling both for researchers and those who evalu-ate research

Detection of Highly Pathogenic Avian Influenza Virus H5N1 Clade 2.3.4.4b in Great Skuas:A Species of Conservation Concern in Great Britain

The UK and Europe have seen successive outbreaks of highly pathogenic avian influenza across the 2020/21 and 2021/22 autumn/winter seasons. Understanding both the epidemiology and transmission of these viruses in different species is critical to aid mitigating measures where outbreaks cause extensive mortalities in both land- and waterfowl. Infection of different species can result in mild or asymptomatic outcomes, or acute infections that result in high morbidity and mortality levels. Definition of disease outcome in different species is of great importance to understanding the role different species play in the maintenance and transmission of these pathogens. Further, the infection of species that have conservation value is also important to recognise and characterise to understand the impact on what might be limited wild populations. Highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b has been detected in great skuas (Stercorarius skua) across different colonies on islands off the shore of Scotland, Great Britain during summer 2021. A large number of great skuas were observed as developing severe clinical disease and dying during the epizootic and mortalities were estimated to be high where monitored. Of eight skuas submitted for post-mortem examination, seven were confirmed as being infected with this virus using a range of diagnostic assays. Here we overview the outbreak event that occurred in this species, listed as species of conservation concern in Great Britain and outline the importance of this finding with respect to virus transmission and maintenance

Detection of SARS‐CoV‐2 in respiratory samples from cats in the UK associated with human‐to‐cat transmission

Objectives: The aim of the study was to find evidence of SARS‐CoV‐2 infection in UK cats. Design: Tissue samples were tested for SARS‐CoV‐2 antigen using immunofluorescence and for viral RNA by in situ hybridisation. A set of 387 oropharyngeal swabs that had been submitted for routine respiratory pathogen testing was tested for SARS‐CoV‐2 RNA using reverse transcriptase quantitative PCR. Results: Lung tissue collected post‐mortem from cat 1 tested positive for both SARS‐CoV‐2 nucleocapsid antigen and RNA. SARS‐CoV‐2 RNA was detected in an oropharyngeal swab collected from cat 2 that presented with rhinitis and conjunctivitis. High throughput sequencing of the viral genome revealed five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS‐CoV‐2 sequence, and this human virus contained eight SNPs compared to the original Wuhan‐Hu‐1 reference sequence. An analysis of the viral genome of cat 2 together with nine other feline‐derived SARS‐CoV‐2 sequences from around the world revealed no shared cat‐specific mutations. Conclusions: These findings indicate that human‐to‐cat transmission of SARS‐CoV‐2 occurred during the COVID‐19 pandemic in the UK, with the infected cats developing mild or severe respiratory disease. Given the ability of the new coronavirus to infect different species, it will be important to monitor for human‐to‐cat, cat‐to‐cat and cat‐to‐human transmission