Canagliflozin Attenuates PromarkerD Diabetic Kidney Disease Risk Prediction Scores.

PromarkerD is a biomarker-based blood test that predicts kidney function decline in people with type 2 diabetes (T2D) who may otherwise be missed by current standard of care tests. This study examined the association between canagliflozin and change in PromarkerD score (Δ score) over a three-year period in T2D participants in the CANagliflozin cardioVascular Assessment Study (CANVAS). PromarkerD scores were measured at baseline and Year 3 in 2008 participants with preserved kidney function (baseline eGFR ≥60 mL/min/1.

Immunoaffinity Mass Spectrometry Diagnostic Tests for Multi-Biomarker Assays.

Immunoaffinity mass spectrometry as an approach for diagnostic biomarker assays combines the advantages of antibody selectivity with the multiplexing and analytical performance of mass spectrometry. A method has been developed to detect and quantify three protein biomarkers for a diabetic kidney disease prognostic assay, PromarkerD. The methodology reflects an immunoaffinity approach compatible with higher throughput and robust clinical application.

ApoE4 Astrocytes Secrete Basement Membranes Rich in Fibronectin and Poor in Laminin Compared to ApoE3 Astrocytes.

The accumulation of amyloid-β (Aβ) in the walls of capillaries and arteries as cerebral amyloid angiopathy (CAA) is part of the small vessel disease spectrum, related to a failure of elimination of Aβ from the brain. Aβ is eliminated along basement membranes in walls of cerebral capillaries and arteries (Intramural Peri-Arterial Drainage-IPAD), a pathway that fails with age and ApolipoproteinEε4 (ApoE4) genotype. IPAD is along basement membranes formed by capillary endothelial cells and surrounding astrocytes.

The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy.

In the absence of lymphatics, fluid and solutes such as amyloid-β (Aβ) are eliminated from the brain along basement membranes in the walls of cerebral capillaries and arteries-the Intramural Peri-Arterial Drainage (IPAD) pathway. IPAD fails with age and insoluble Aβ is deposited as plaques in the brain and in IPAD pathways as cerebral amyloid angiopathy (CAA); fluid accumulates in the white matter as reflected by hyperintensities (WMH) on MRI. Within the brain, fluid uptake by astrocytes is regulated by aquaporin 4 (AQP4).

Descriptive analysis of ovine mortality in sentinel sheep flocks in Ireland.

Background: Studies of sheep mortality or cause-specific mortality, in Ireland or internationally, are relatively scarce but are important in presenting baseline levels and changing trends of endemic disease. This study assessed sheep mortality and cause-specific mortality in 33 sentinel sheep flocks in Ireland.

Methods: Sentinel flocks were requested to submit carcases of all sheep that died to the regional veterinary laboratories (RVLs) of the Department of Agriculture, Food and Marine during a calendar year (2016).

Investigation of the potential for sera from cattle persistently infected with bovine viral diarrhea virus to generate false-negative antibody ELISA results in pooled serum from seropositive and seronegative cattle.

We investigated the potential for viremic sera from cattle persistently infected with bovine viral diarrhea virus to create false-negative antibody results when testing pools of 10 sera by indirect or blocking ELISAs. Seronegative viremic sera ( n = 23) were each added to a series of artificially constructed pools containing various percentages (0-90%) of antibody-positive sera, and the resulting pools were assayed for antibody. In all 23 cases, a negative antibody result was obtained in the pool containing no seropositive sera.

Sampling Methodology to Maximize the Efficient Use of National Abattoir Surveillance: Using Archived Sera to Substantiate Freedom From Bluetongue Virus Infection in Ireland.

In recent years, there has been increasing recognition of the value of multiple data sources available to fulfill surveillance objectives, and the use of these has been applied to address many questions relating to animal health surveillance. In Ireland, we face a slightly different problem, namely, best use of an existing surveillance resource (serological samples collected over many years from cull cows at slaughter), which has been used to substantiate freedom from following its successful eradication in 2009. In this study, we evaluate a sampling methodology to use this resource to substantiate freedom from bluetongue virus (BTV) infection.

Risk factors associated with exposure to bovine respiratory disease pathogens during the peri-weaning period in dairy bull calves.

Background: Bovine respiratory disease (BRD) remains among the leading causes of death of cattle internationally. The objective of this study was to identify risk factors associated with exposure to BRD pathogens during the peri-weaning period (day (d)-14 to d 14 relative to weaning at 0) in dairy bull calves using serological responses to these pathogens as surrogate markers of exposure. Clinically normal Holstein-Friesian and Jersey breed bull calves (n = 72) were group housed in 4 pens using a factorial design with calves of different breeds and planes of nutrition in each pen.

First confirmation by PCR of Jaagsiekte sheep retrovirus in Ireland and prevalence of ovine pulmonary adenocarcinoma in adult sheep at slaughter.

Background: Ovine pulmonary adenocarcinoma (OPA), caused by Jaagsiekte sheep retrovirus (JSRV), is characterised by the development of invariably fatal lung tumours primarily in adult sheep. High infection rates and disease prevalence can develop during initial infection of flocks, leading to on-farm economic losses and animal welfare issues in sheep with advanced disease. The disease has been reported in Ireland and is notifiable, but the presence of JSRV has never been confirmed using molecular methods in this country.

Hypothetical route of the introduction of Schmallenberg virus into Ireland using two complementary analyses.

Ireland lost its official freedom from Schmallenberg virus (SBV) in October 2012. The route of introduction is uncertain, with long-distance displacement of infected , biting midges, by suitable wind flows considered to be the most likely source. The authors investigated the potential introduction of SBV into Ireland through a incursion event in the summer of 2012.

A survey of free-ranging deer in Ireland for serological evidence of exposure to bovine viral diarrhoea virus, bovine herpes virus-1, bluetongue virus and Schmallenberg virus.

Background: Deer are an important wildlife species in both the Republic of Ireland and Northern Ireland having colonised most regions across the island of Ireland. In comparison to cattle and sheep which represent the main farmed ruminant species on the island, there is a lack of data concerning their exposure, as measured by the presence of antibodies, to important viral pathogens of ruminants. A study was therefore undertaken to investigate the seroprevalence of wild deer to four viruses, namely bovine viral diarrhoea virus (BVDV), bovine herpesvirus-1 (BoHV-1), Schmallenberg virus (SBV) and bluetongue virus (BTV).

The bovine paranasal sinuses: Bacterial flora, epithelial expression of nitric oxide and potential role in the in-herd persistence of respiratory disease pathogens.

The bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD) persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents.

Pathogens, patterns of pneumonia, and epidemiologic risk factors associated with respiratory disease in recently weaned cattle in Ireland.

We examined the pathogens, morphologic patterns, and risk factors associated with bovine respiratory disease (BRD) in 136 recently weaned cattle ("weanlings"), 6-12 mo of age, that were submitted for postmortem examination to regional veterinary laboratories in Ireland. A standardized sampling protocol included routine microbiologic investigations as well as polymerase chain reaction and immunohistochemistry. Lungs with histologic lesions were categorized into 1 of 5 morphologic patterns of pneumonia.

Evolving views on bovine respiratory disease: An appraisal of selected key pathogens - Part 1.

Bovine respiratory disease (BRD) is one of the most commonly diagnosed causes of morbidity and mortality in cattle and interactions of factors associated with the animal, the pathogen and the environment are central to its pathogenesis. Emerging knowledge of a role for pathogens traditionally assumed to be minor players in the pathogenesis of BRD reflects an increasingly complex situation that will necessitate regular reappraisal of BRD pathogenesis and control. This review appraises the role of selected key pathogens implicated in BRD pathogenesis to assess how our understanding of their role has evolved in recent years.

Evolving views on bovine respiratory disease: An appraisal of selected control measures - Part 2.

Bovine respiratory disease (BRD) control poses significant challenges to the cattle industry worldwide. The sometimes complex interactions of factors associated with the animal, the pathogen and the environment complicate the implementation of effective control measures. Blanket vaccination or mass medication provides inconsistent control and the effective tackling of BRD will require innovative, evidence-based and targeted interventions which, if employed sensibly, offer useful alternatives for addressing this disease.

The impact of infection with Schmallenberg virus on weaning rate in Irish sheep flocks.

Schmallenberg virus (SBV) disease emerged in Europe in 2011, with the virus initially identified in Germany, and the first confirmed case of SBV infection in Ireland diagnosed in a dairy calf in October 2012. SBV was subsequently confirmed by RT-PCR in 49 cattle herds and 39 sheep flocks. While these studies provide a good representation of the spatial distribution of SBV in Ireland, they do not quantify the impact of SBV on productivity.

Genetic diversity of ruminant Pestivirus strains collected in Northern Ireland between 1999 and 2011 and the role of live ruminant imports.

Background: The genus pestivirus within the family Flaviviridae includes bovine viral diarrhoea virus (BVDV) types 1 and 2, border disease virus (BDV) and classical swine fever virus. The two recognised genotypes of BVDV are divided into subtypes based on phylogenetic analysis, namely a-p for BVDV-1 and a-c for BVDV-2.

Methods: Three studies were conducted to investigate the phylogenetic diversity of pestiviruses present in Northern Ireland.

Bioexclusion of diseases from dairy and beef farms: risks of introducing infectious agents and risk reduction strategies.

Infectious disease represents a major threat to the productivity and welfare of cattle herds throughout the world. The introduction of infectious agents into dairy and beef farms may be through direct transmission (purchased cattle, reintroduced resident cattle and contact with contiguous cattle) or indirect transmission (fomites, visitors, other species, and biological materials) and this article reviews the evidence supporting these transmission routes. In the absence of eradication programmes for many endemic infectious diseases, bioexclusion is the key management process for risk reduction.

Quantitative trait loci associated with the immune response to a bovine respiratory syncytial virus vaccine.

Infectious disease is an important problem for animal breeders, farmers and governments worldwide. One approach to reducing disease is to breed for resistance. This linkage study used a Charolais-Holstein F2 cattle cross population (n = 501) which was genotyped for 165 microsatellite markers (covering all autosomes) to search for associations with phenotypes for Bovine Respiratory Syncytial Virus (BRSV) specific total-IgG, IgG1 and IgG2 concentrations at several time-points pre- and post-BRSV vaccination.

A survey of antibodies to pestivirus in sheep in the Republic of Ireland.

: Sera from 1,448 adult ewes in 91 flocks, representing all 26 counties in the Republic of Ireland, were examined for pestivirus antibodies using a commercially available ELISA which detected IgG1 antibody to border disease virus. Eighty-one sheep (5.6%) in 42 flocks (46.

Absence of evidence of porcine circovirus infection in piglets with congenital tremors.

Porcine circovirus types 1 (PCV1) and 2 (PCV2) have been associated with congenital tremors (CTs) in piglets in the United States. In this study, central nervous system and nonneural tissues of 40 CT piglets from Spain, the United Kingdom, Ireland, and Sweden were investigated for the presence of PCV1 and PCV2 using in situ hybridization and immunohistochemical labeling on paraffin sections. The polymerase chain reaction for PCV2 was also carried out on sera from the Spanish CT cases.