AMYLOIDOSIS IN CAPTIVE EUROPEAN EASTERN BONGO (TRAGELAPHUS EURYCERUS ISAACI): PREVALENCE, PREDICTIVE FACTORS, ORGAN PREDILECTION, AND SERUM AMYLOID A CONCENTRATIONS.

Amyloidosis is frequently identified during postmortem examination of captive eastern bongo (Tragelaphus eurycerus isaaci) in the European Endangered Species Programme (EEP). However, its significance and etiopathogenesis are poorly understood. The objective of this study was to investigate the prevalence of amyloidosis within this population and identify potential predictive factors for the presence of disease. Postmortem reports obtained from 24 EEP institutions were analyzed and assessed for evidence of amyloidosis. Seventy-two individuals had histopathological assessment performed after gross postmortem examination and were included in the study. Further histopathological analysis was performed on Congo red-stained slides from 26 individuals, and organ predilection sites were identified. Immunohistochemical analysis was performed in six individuals to identify the type of amyloid present. Serum amyloid A (SAA) analysis was performed on blood samples from 34 individuals, and concentrations in affected and unaffected individuals were compared. Amyloidosis was reported in 26 animals (36%). The association between the presence of amyloidosis and sex, age, or body condition was not statistically significant. However, amyloidosis was not identified in any individuals under the age of 6 yr. The presence of chronic inflammatory conditions was the only statistically significant predictive factor for the presence of amyloidosis (P = 0.03). Chronic inflammatory conditions present included nephritis, enteritis, and pneumonia. The majority of affected animals presented with amyloid deposition in multiple organs, with the liver and kidneys being most commonly affected. Immunohistochemistry confirmed the presence of AA amyloid. The association between the presence of amyloidosis and SAA values measured on a single occasion was not statistically significant. This study identified a high prevalence of amyloidosis within the captive European eastern bongo population associated with chronic inflammatory conditions. Antemortem diagnosis of amyloidosis remains challenging, and this study indicates that SAA protein concentrations are not a reliable indicator for the presence of amyloidosis.

Inequality in socio-emotional skills: A cross-cohort comparison.

We examine changes in inequality in socio-emotional skills very early in life in two British cohorts born 30 years apart. We construct comparable scales using two validated instruments for the measurement of child behaviour and identify two dimensions of socio-emotional skills: 'internalising' and 'externalising'. Using recent methodological advances in factor analysis, we establish comparability in the inequality of these early skills across cohorts, but not in their average level. We document for the first time that inequality in socio-emotional skills has increased across cohorts, especially for boys and at the bottom of the distribution. We also formally decompose the sources of the increase in inequality and find that compositional changes explain half of the rise in inequality in externalising skills. On the other hand, the increase in inequality in internalising skills seems entirely driven by changes in returns to background characteristics. Lastly, we document that socio-emotional skills measured at an earlier age than in most of the existing literature are significant predictors of health and health behaviours. Our results show the importance of formally testing comparability of measurements to study skills differences across groups, and in general point to the role of inequalities in the early years for the accumulation of health and human capital across the life course.

The influence of viral RNA secondary structure on interactions with innate host cell defences.

RNA viruses infecting vertebrates differ fundamentally in their ability to establish persistent infections with markedly different patterns of transmission, disease mechanisms and evolutionary relationships with their hosts. Although interactions with host innate and adaptive responses are complex and persistence mechanisms likely multi-factorial, we previously observed associations between bioinformatically predicted RNA secondary formation in genomes of positive-stranded RNA viruses with their in vivo fitness and persistence. To analyse this interactions functionally, we transfected fibroblasts with non-replicating, non-translated RNA transcripts from RNA viral genomes with differing degrees of genome-scale ordered RNA structure (GORS). Single-stranded RNA transcripts induced interferon-ß mediated though RIG-I and PKR activation, the latter associated with rapid induction of antiviral stress granules. A striking inverse correlation was observed between induction of both cellular responses with transcript RNA structure formation that was independent of both nucleotide composition and sequence length. The consistent inability of cells to recognize RNA transcripts possessing GORS extended to downstream differences from unstructured transcripts in expression of TNF-α, other interferon-stimulated genes and induction of apoptosis. This functional association provides novel insights into interactions between virus and host early after infection and provides evidence for a novel mechanism for evading intrinsic and innate immune responses.

Diversity of murine norovirus in wild-rodent populations: species-specific associations suggest an ancient divergence.

A survey of wild-rodent populations has revealed that murine norovirus (MNV) is present and diverse in wild-house mice Mus musculus. This virus is genetically similar to MNV infecting show mice and previously described variants circulating in laboratory mice. The detection of MNV in wild-mouse populations suggests that MNV infection of laboratory mice and show mice (from which laboratory mice are derived) derives from contact with or their origins from wild-mouse progenitors. The survey additionally identified frequent infection of wood mice (Apodemus sylvaticus) with genetically divergent variants of MNV. These viruses are distinct from previously described MNV variants, differing by 22-23 % over the complete genome sequence compared with a maximum of 13 % between M. musculus-derived strains. Comparison with other noroviruses reveals that the Apodemus MNV groups with MNV in genogroup V and shares the same overall genome organization, predicted lengths of proteins encoded by ORFs 1-3 and the existence of a conserved alternative reading frame in VP1 encoding a homologue of the MNV ORF4. Different Apodemus MNV isolates were as variable as MNV isolates and showed evidence for inter-isolate recombination. Our observation of species-specific associations of MNV variants in wild populations suggests that murine noroviruses have an ancient origin, a feature that they may share with other norovirus genogroups.

The Forensic Pathology of the Sexual Abuse of a Group of Chickens.

Twelve chickens were discovered dead in a barn with a human male suspect observed on closed-circuit television. Post-mortem examination of two of the chickens revealed traumatic injury to the ventral cloaca with fibrinoheterophilic coelomitis associated with coelomic contamination by gut contents. The presence of human DNA was subsequently confirmed in cloacal swabs. This report highlights animal sexual abuse, which may occur in a range of species including chickens, as a significant challenge to animal welfare. Veterinary surgeons should be vigilant for signs of injury to the anogenital regions of animal patients, including birds, as evidence of potential sexual abuse.

Clinical and Pathological Features of Bovine Ischaemic Teat Necrosis.

Bovine ischaemic teat necrosis (ITN) is an emerging disease of unknown aetiology affecting mostly dairy cows in the early stages of first lactation and a substantial welfare concern frequently leading to premature culling and economic losses. Specific diagnostic criteria are lacking. The aims of this study were to develop an appropriate ITN grading system, describe the histopathological changes and investigate the potential aetiological role of several pathogens in 47 cows with 73 ITN lesions from 28 farms. ITN lesions were allocated to one of three broad macroscopic categories: presence of a non-proliferative lesion on the teat (type 1); proliferative teat lesion with crusting (type 2); severe purulent to eosinophilic, ulcerative and necrotising dermatitis and sloughing or total absence of the teat (type 3). Lesions were mostly observed on the medial aspect of the teat but there was no anatomical predisposition as to which teats were more frequently affected. In approximately 50% of the ITN teats reviewed, the lesions were continuous with the skin of the udder and 34.2% of cases had sloughed or partially sloughed teats. The main histological findings were: focally extensive severe purulent to eosinophilic, ulcerative and necrotizing dermatitis; serocellular crust formation; and epidermal hyperplasia with dyskeratosis. Some lesions also had leucocytoclastic to eosinophilic vasculitis and thrombosis with ischaemic necrosis. Macroscopic and histological analyses confirmed the suspected ischaemic nature of the lesions but the specific aetiopathogenesis was elusive with a wide range of bacteria present, probably as opportunistic infections. However, Treponema spp and Orthopox virus were excluded as major aetiological agents. This study establishes a foundation for further investigations of the pathogenesis of bovine ITN and a basis for consistency in diagnosis and classification of the stage of disease. The findings are also key to further understanding disease progression and prognosis.

Could COVID-19 Infect the Consumer Prices Index?

The spread of COVID-19 has led to sweeping changes in the way households work, spend their time and shop, resulting in different shopping patterns and rapid price changes in some goods. How will changes such as these be reflected in headline inflation measures such as the Consumer Prices Index (CPI)? This paper discusses problems in interpreting the CPI as a measure of how the cost of living is changing during the lockdown.

COVID-19 and Inequalities.

This paper brings together evidence from various data sources and the most recent studies to describe what we know so far about the impacts of the COVID-19 crisis on inequalities across several key domains of life, including employment and ability to earn, family life and health. We show how these new fissures interact with existing inequalities along various key dimensions, including socio-economic status, education, age, gender, ethnicity and geography. We find that the deep underlying inequalities and policy challenges that we already had are crucial in understanding the complex impacts of the pandemic itself and our response to it, and that the crisis does in itself have the potential to exacerbate some of these pre-existing inequalities fairly directly. Moreover, it seems likely that the current crisis will leave legacies that will impact inequalities in the long term. These possibilities are not all disequalising, but many are.

The use of chicken and insect infection models to assess the virulence of African Salmonella Typhimurium ST313.

Over recent decades, Salmonella infection research has predominantly relied on murine infection models. However, in many cases the infection phenotypes of Salmonella pathovars in mice do not recapitulate human disease. For example, Salmonella Typhimurium ST313 is associated with enhanced invasive infection of immunocompromised people in Africa, but infection of mice and other animal models with ST313 have not consistently reproduced this invasive phenotype. The introduction of alternative infection models could help to improve the quality and reproducibility of pathogenesis research by facilitating larger-scale experiments. To investigate the virulence of S. Typhimurium ST313 in comparison with ST19, a combination of avian and insect disease models were used. We performed experimental infections in five lines of inbred and one line of outbred chickens, as well as in the alternative chick embryo and Galleria mellonella wax moth larvae models. This extensive set of experiments identified broadly similar patterns of disease caused by the African and global pathovariants of Salmonella Typhimurium in the chicken, the chicken embryo and insect models. A comprehensive analysis of all the chicken infection experiments revealed that the African ST313 isolate D23580 had a subtle phenotype of reduced levels of organ colonisation in inbred chickens, relative to ST19 strain 4/74. ST313 isolate D23580 also caused reduced mortality in chicken embryos and insect larvae, when compared with ST19 4/74. We conclude that these three infection models do not reproduce the characteristics of the systemic disease caused by S. Typhimurium ST313 in humans.

Introducing forensic entomology in cases of suspected animal neglect.

Cases of arthropod-infested, abandoned or abused animals are sometimes brought to the attention of veterinarians by animal welfare authorities, with the requirement for a full postmortem examination towards criminal or civil proceedings. In these situations, entomology is an important support tool for the pathologists' investigation since the presence of arthropod life cycle stages serve as reliable forensic markers, especially for blowflies which form the first waves of activity following death. In the present study, 70 cadavers from a total of 544 referred to the Institute of Veterinary Science, University of Liverpool, between 2009 and 2014 displayed evidence of infestation. Here, the authors introduce principles of applied entomology and simplified approaches for estimating the minimum time since death, relevant in the context of routine submissions and the broad remit of individual cases. Despite often limited availability of scene of the crime and local thermal data, the interpretation of the minimum postmortem interval has nonetheless proved valuable as an adjunct to the expert pathology report. However, future developments and enhanced accuracy in this area of animal welfare require resource and training in expertise, and agreed standardisation of both laboratory and field procedures.

Ultrasonographic appearance of the major duodenal papilla in dogs without evidence of hepatobiliary, pancreatic, or gastrointestinal tract disease.

OBJECTIVE To determine the ultrasonographic appearance of the major duodenal papilla (MDP) in dogs without evidence of hepatobiliary, pancreatic, or gastrointestinal tract disease. ANIMALS 40 adult client-owned dogs examined because of conditions that did not include hepatobiliary, pancreatic, or gastrointestinal tract disease. PROCEDURES Ultrasonographic examination of the MDP was performed. Each MDP was measured in 3 planes. Intraobserver reliability of measurements was determined, and associations between MDP dimensions and characteristics of the dogs were investigated. Histologic examination of longitudinal sections of the MDP was performed for 1 dog to compare the ultrasonographic and histologic appearance. RESULTS The MDP appeared as a layered structure with a hyperechoic outer layer, hypoechoic middle layer, and hyperechoic inner layer that corresponded to the duodenal serosa, duodenal muscularis, and duodenal submucosa, respectively. Layers visible during ultrasonographic examinations were consistent with layers identified histologically. Intraobserver reliability was substantial for each plane of measurement. Mean ± SD length, width, and height of the MDP were 15.2 ± 3.5 mm, 6.3 ± 1.6 mm, and 4.3 ± 1.0 mm, respectively. An increase in body weight of dogs was significantly associated with increased values for all measurements. CONCLUSIONS AND CLINICAL RELEVANCE The ultrasonographic appearance and approximate dimensions of the MDP of dogs without evidence of hepatobiliary, pancreatic, or gastrointestinal tract disease were determined. Additional studies are needed to evaluate possible ultrasonographic lesions of the MDP in dogs with hepatobiliary, pancreatic, or intestinal diseases and to investigate clinical implications of these lesions with regard to diagnosis and prognosis.

Housing Mobility and Downsizing at Older Ages in Britain and the United States.

This paper examines geographic mobility and housing downsizing at older ages in Britain and America. Americans downsize housing much more than the British largely because Americans are much more mobile. The principal reasons for greater mobility among older Americans are two fold: (1) greater spatial distribution of geographic distribution of amenities (such as warm weather) and housing costs and (2) greater institutional rigidities in subsidized British rental housing providing stronger incentives for British renters not to move. This relatively flat British housing consumption with age may have significant implications for the form and amount of consumption smoothing at older ages.

Optimizing aerosol gene delivery and expression in the ovine lung.

We have developed the sheep as a large animal model for optimizing cystic fibrosis gene therapy protocols. We administered aerosolized gene transfer agents (GTAs) to the ovine lung in order to test the delivery, efficacy, and safety of GTAs using a clinically relevant nebulizer. A preliminary study demonstrated GTA distribution and reporter gene expression throughout the lung after aerosol administration of plasmid DNA (pDNA):GL67 and pDNA:PEI complexes. A more comprehensive study examined the dose-response relationship for pDNA:PEI and assessed the influence of adjunct therapeutic agents. We found that the sheep model can differentiate between doses of GTA and that the anticholinergic, glycopyrrolate, enhanced transgene expression. Dose-related toxicity of GTA was reduced by aerosol administration compared to direct instillation. This large animal model will allow us to move toward clinical studies with greater confidence.

Electroporation enhances reporter gene expression following delivery of naked plasmid DNA to the lung.

BACKGROUND: Existing methods of non-viral airway gene transfer suffer from low levels of efficiency. Electroporation has been used to enhance gene transfer in a range of tissues. Here we assess the usefulness of electroporation for enhancing gene transfer in the lungs of mice and sheep. METHODS: Naked plasmid DNA (pDNA) expressing either luciferase or green fluorescent protein (GFP) was delivered to mouse lungs by instillation. Following surgical visualisation, the lungs were directly electroporated and the level and duration of luciferase activity was assessed and cell types that were positive for GFP were identified in lung cryosections. Naked pDNA was nebulised to the sheep lung and electrodes attached to the tip of a bronchoscope were used to electroporate airway segment bifurcations, Luciferase activity was assessed in electroporated and control non-electroporated regions, after 24 h. RESULTS: Following delivery of naked pDNA to the mouse lung, electroporation resulted in up to 400-fold higher luciferase activity than naked pDNA alone when luciferase was under the control of a cytomegalovirus (CMV) promoter. Following delivery of a plasmid containing the human polyubiquitin C (UbC) promoter, electroporation resulted in elevated luciferase activity for at least 28 days. Visualisation of GFP indicated that electroporation resulted in increased GFP detection compared with non-electroporated controls. In the sheep lung electroporation of defined sites in the airways resulted in luciferase activity 100-fold greater than naked pDNA alone. CONCLUSIONS: These results indicate that electroporation can be used to enhance gene transfer in the lungs of mice and sheep without compromising the duration of expression.

Local lung responses following endobronchial elastase and lipopolysaccharide instillation in sheep.

Chronic lipopolysaccharide (LPS) exposure may contribute to the pathogenesis of a number of lung diseases including COPD and emphysema. We sought to develop a large-animal model of emphysema using repeated LPS administration into sheep lung segments. An experimental protocol was designed to facilitate comparisons with elastase-treated and control segments within the same lung of individual sheep. Histopathologic evaluation of segments treated with LPS demonstrated low-grade inflammation characterized by an increase in the number of intra-alveolar macrophages and lymphocytes. Treated segments demonstrated a significant reduction in airspace surface area (ASA), an increase in percent disrupted alveolar attachments and the distance between normal alveolar attachments, and a reduction in the number of normal alveolar attachments surrounding nonrespiratory bronchioles. Coefficient of variation of individual ASA measurements in elastase-treated segments was indicative of a heterogeneous parenchymal response, in contrast to that associated with chronic LPS treatment. Our results demonstrate that chronic LPS treatment of individual lung segments in sheep induces microscopic emphysema qualitatively and quantitatively consistent with both accepted pathologic definitions of this condition and with that produced by airway instillation of elastolytic enzymes. Development of this phenotype is associated with evidence of downregulated activation of transforming growth factor beta.