RESUMEN
Herd-level bovine tuberculosis (bTB) incidence was examined in the Burren, an area in the west of Ireland where herd owners practice distinctive transhumance practices, with upland winter grazing. Prior to the initiation of our study in 2020, bTB incidence had for many years been unusually high in the Burren in comparison with the rest of the country, although the most recent figures have come down to being closer to the national average. Using data from the period prior to 2020, we mapped bTB infection in Burren herds alongside a range of indicators thought to have an association with it - herd size, herd density, herd type, cattle movement, and badger (Meles meles) population and control data, as well as rainfall and altitude. We also looked at how summary statistics for these variables differed when Burren herds with a history of bTB were compared to other Burren herds, as well as bTB positive and negative herds from outside the Burren. We found that for many indicators Burren herds would be expected to be low risk when compared to other herds in Ireland. An exception to this was for rainfall: hot spot areas for bTB in the Burren were found in areas of higher rainfall, on average herds in the Burren experienced more rainfall than those outside it, and bTB herds in the Burren experienced higher rainfall than non-bTB herds. Separately, for Burren herds only, a logistic regression model was developed to explain bTB breakdown occurrence using a matched case-control approach. Cases were herds which had experienced a new bTB breakdown between 2015 and 2019 (n = 260) and these were matched on herd type and herd size with the same number of herds not experiencing a breakdown during this period. This showed that, of a range of exogenous variables, rainfall was the most strongly associated with herd-level bTB incidence. These results suggest that high levels of exposure to inclement weather, and/or better environmental survival of Mycobacterium bovis in the environment, may contribute to high bTB rates in the Burren. However, as rainfall showed a highly aggregated distribution, this relationship may be due to an unmeasured factor correlated with it. Mapping and graphical output suggested that, although herd sizes in the Burren were on average lower than nationally, within the Burren they were higher in areas of higher prevalence, suggesting that mechanisms associated with herd size, such as increased contacts between and within herd, and with wildlife, may also play a role.
RESUMEN
Bovith recene tuberculosis (bTB) continues to be a pathogen of concern in several countries globally. Analysis of areas that have higher incidences of bTB outbreaks has demonstrated how risk is not equally distributed, and local data collection, analysis and participatory engagement is required to develop tailored approaches. The Burren, an internationally important heritage landscape, has been an area of higher bTB incidence for many years in Ireland, and owing to its unique geology and farming heritage a survey was developed to engage with local farmers to gain greater insight into farming practices and bTB control to inform tailored approaches. The survey gathered data on the farm and animal management approaches being used within the Burren, including local farming techniques like the use of "winterage" (grazing exposed limestone dominated uplands). Thematic analysis of free text responses was undertaken. Quantitative data were then explored using statistical models to assess associations with recent (<3 years) self-reported bTB breakdown risk. There was a high number of responses demonstrating a high degree of willingness to engage on the issue. Thematic analysis suggested that wildlife and its management (culling and vaccination), testing quality, and its impact on the bTB scheme, and pessimism around eradication were important themes. Statistical analysis suggested that increasing bTB risk was primarily related to increasing herd-size and the percentage of herd owner's land inaccessible to those attempting to locate badger setts. There was less evidence for associations relating to the amount of time, or which season (i.e., summer), farmers utilized "winterage". The results of the study will feed back directly to local bTB management plans and further stakeholder engagement and is an exemplar for local tailoring of national control measures in situations of high incidences of bTB outbreaks in particular areas.
RESUMEN
BACKGROUND: Pre-eclampsia (PE) is associated with vascular endothelial dysfunction and oxidative stress initiated by impaired trophoblast invasion. Oxidative stress modifies circulating low-density lipoprotein (LDL) to oxidized LDL (oxLDL). Lectin-like oxLDL receptor-1 (LOX-1) is a scavenger receptor for oxLDL. We hypothesized that plasma from patients with PE alters LOX-1 in normal human vessels during pregnancy, causing oxLDL-induced impairment of vascular function. METHODS: Control-matched plasma was obtained from women with PE (n = 6). Oxidized LDL and soluble LOX-1 levels were determined by enzyme-linked immunoassay (ELISA). Remaining plasma was pooled and stored at -80ºC. Human omental arteries were incubated in 3% plasma from normal pregnant (NP) women or plasma from women with PE. Expression of LOX-1 in these vessels was determined by immunohistochemistry with antibodies against LOX-1. The omental vessels were exposed to oxLDL and the LOX-1 inhibitor TS20. Vascular function was assessed in response to the vasoconstrictor U46619 and the vasodilators bradykinin (BK) and sodium nitroprusside (SNP). RESULTS: No significant differences in the concentrations of oxLDL or soluble LOX-1 (sLOX-1) were found in plasma from women with PE as compared with NP women. The expression of LOX-1 was not significantly different in either the NP or PE incubated omental vessels. Incubation of vessels from NP women in plasma from women with PE impaired their relaxation in response to BK as compared with that of NP vessels incubated in plasma from NP women. Exposure to oxLDL further impaired relaxation in NP vessels incubated with plasma from women with PE. Inhibition of LOX-1 protected against the impairment of vascular relaxation induced by plasma from women with PE. CONCLUSION: Inhibition of LOX-1 prevents endothelial dysfunction in an in vitro model of PE and may prove useful as a therapeutic target in the treatment of PE.