No abstract

Chronic hypertension (HTN) affects more than 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease. Despite decades of promising research, effective treatment of HTN remains challenging. This work investigates vagus nerve stimulation (VNS) as a novel, device-based therapy for HTN treatment, and specifically evaluates its effects on long-term survival and HTN-associated adverse effects. HTN was induced in Dahl salt-sensitive rats using a high-salt diet, and the rats were randomly divided into two groups: VNS (n = 9) and Sham (n = 8), which were implanted with functional or non-functional VNS stimulators, respectively. Acute and chronic effects of VNS therapy were evaluated through continuous monitoring of blood pressure (BP) and ECG via telemetry devices. Autonomic tone was quantified using heart rate (HR), HR variability (HRV) and baroreflex sensitivity (BRS) analysis. Structural cardiac changes were quantified through gross morphology and histology studies. VNS significantly improved the long-term survival of hypertensive rats, increasing median event-free survival by 78% in comparison to Sham rats. Acutely, VNS improved autonomic balance by significantly increasing HRV during stimulation, which may lead to beneficial chronic effects of VNS therapy. Chronic VNS therapy slowed the progression of HTN through an attenuation of SBP and by preserving HRV. Finally, VNS significantly altered cardiac structure, increasing heart weight, but did not alter the amount of fibrosis in the hypertensive hearts. These results suggest that VNS has the potential to improve outcomes in subjects with severe HTN.

No abstract

Lawsonia intracellularis , an obligate intracellular bacterium, is an important enteric pathogen in pig herds and horse farms worldwide. The hallmark feature of L. intracellularis infection is the proliferation of epithelial cells in intestinal crypts. A major limitation to the study of L. intracellularis infection is the lack of an in vitro model that reproduces the changes observed in proliferative enteropathy. Here we investigated the suitability of mouse enteroids as a model to study L. intracellularis infection. Mouse enteroids were microinjected with L. intracellularis , filter-sterilized L. intracellularis culture supernatant, or sterile cell culture media (DMEM). L. intracellularis antigen was detected in mouse enteroids by immunohistochemistry and was located mostly in the basal region of the epithelium. There was no differential growth of enteroids among treatment groups, and cellular proliferation was not increased in L. intracellularis -infected enteroids in relation to non-infected enteroids based on immunofluorescence staining. L. intracellularis infection did not induce changes in gene expression of Ki - 67 (proliferation marker), Sox9 (marker for transit amplifying cells) and Muc2 (marker for goblet cells). These results indicate that although L. intracellularis antigen is detectable in mouse enteroids, indicating susceptibility to infection, mouse enteroids fail to replicate the cellular proliferation and gene expression changes observed in proliferative enteropathy. Nevertheless, we have successfully demonstrated that mouse enteroids can be used to model days-long intracellular pathogen infection, serving as potential models for the study of other pathogens of interest in veterinary medicine.

Paroxysmal atrial fibrillation (Paro. AF) is challenging to identify at the right moment. This disease is often undiagnosed using currently existing methods. Nonlinear analysis is gaining importance due to its capability to provide more insight into complex heart dynamics. The aim of this study is to use several recently developed nonlinear techniques to discriminate persistent AF (Pers. AF) from normal sinus rhythm (NSR), and more importantly, Paro. AF from NSR, using short-term single-lead electrocardiogram (ECG) signals. Specifically, we adapted and modified the time-delayed embedding method to minimize incorrect embedding parameter selection and further support to reconstruct proper phase plots of NSR and AF heart dynamics, from MIT-BIH databases. We also examine information-based methods, such as multiscale entropy (MSE) and kurtosis (Kt) for the same purposes. Our results demonstrate that embedding parameter time delay ( τ ), as well as MSE and Kt values can be successfully used to discriminate between Pers. AF and NSR. Moreover, we demonstrate that τ and Kt can successfully discriminate Paro. AF from NSR. Our results suggest that nonlinear time-delayed embedding method and information-based methods provide robust discriminating features to distinguish both Pers. AF and Paro. AF from NSR, thus offering effective treatment before suffering chaotic Pers. AF.