for a one-Health investigation of antimicrobial resistance (AMR) in Enterococcus spp., isolates from humans and beef cattle along with abattoirs, manured fields, natural streams, and wastewater from both urban and cattle feedlot sources were collected over two years. Species identification of Enterococcus revealed distinct associations across the continuum. Of the 8430 isolates collected, Enterococcus faecium and Enterococcus faecalis were the main species in urban wastewater (90%) and clinical human isolates (99%); Enterococcus hirae predominated in cattle (92%) and feedlot catch-basins (60%), whereas natural streams harbored environmental Enterococcus spp. Wholegenome sequencing of E. faecalis (n = 366 isolates) and E. faecium (n = 342 isolates), revealed source clustering of isolates, indicative of distinct adaptation to their respective environments. phenotypic resistance to tetracyclines and macrolides encoded by tet(M) and erm(B) respectively, was prevalent among Enterococcus spp. regardless of source. for E. faecium from cattle, resistance to β-lactams and quinolones was observed among 3% and 8% of isolates respectively, compared to 76% and 70% of human clinical isolates. clinical vancomycin-resistant E. faecium exhibited high rates of multi-drug resistance, with resistance to all β-lactam, macrolides, and quinolones tested. Differences in the AMR profiles among isolates reflected antimicrobial use practices in each sector of the One-Health continuum. Public concern for antimicrobial use (AMU) and resistance (AMR) in livestock is increasing, as is continuing pressure for industries and governments to address these concerns. Science-based and epidemiologically sound research is critical to drive policy, communication, legislation, and inform consumer choices. To effectively investigate the current state of antimicrobial resistance, holistic One Health approaches are required to determine correlation between AMU and AMR across the human-agriculture-environment continuum. The genus Enterococcus is ubiquitous in nature and member species can be found in a range of habitats including soils, sediments, freshwater, marine water, beach sand, and a variety of plants 1,2. Enterococcus spp. are also common members of the normal gastrointestinal (GI) flora of both livestock and humans 3 , with their concentrations in human and animal feces typically ranging from 10 3-10 7 cells per gram 4-6. Enterococcus spp. are also commonly isolated from water contaminated by sewage or fecal wastes, and are widely used as bacteriological

Inflammation plays a central pathogenic role in the initiation and progression of coronary atheroma and its clinical consequences.

It is well recognised that oestrogens possess vasodilatory properties, and similar responses to testosterone have been demonstrated. However, vasomotor effects of other steroid hormones have not been well described. Direct comparisons of the relative vasoactivity of different steroid hormones in different vascular beds in male and female genders have not been made. Coronary and pulmonary arteries from adult Wistar rats were mounted in a wire myograph, loaded to 100 and 17 mmHg respectively, maximally pre-contracted with 1 x 10(-4) M prostaglandin-F-2-alpha, and dose response curves to 1 x 10(-6) to 1 x 10(-3) or 3 x 10(-3) M of 17 beta-oestradiol, testosterone, progesterone, and cortisol dissolved in water were constructed. Addition of each steroid hormone caused acute, dose dependent dilatation in coronary and pulmonary vessels. In coronary arteries the order of activity was testosterone > progesterone > 17 beta-oestradiol > cortisol, p < 0.001. In pulmonary arteries, the order of activity was progesterone > testosterone > cortisol > 17 beta-oestradiol, p < 0.001. Pulmonary arteries from male animals were more sensitive to the effects of testosterone than those from female animals, p = 0.003, whereas coronary arteries from female animals were more sensitive to the effects of 17 beta-oestradiol than those from male animals, p < 0.001. We have demonstrated significant differences in the in vitro vasomotor effects of different steroid hormones in two distinct vascular beds. Gender differences in vasomotor responses to steroid hormones may play a role in the aetiology of vasospastic diseases.

Background-Research supports a beneficial effect of physiological testosterone on cardiovascular disease. The mechanisms by which testosterone produces these effects have yet to be elucidated. The testicular feminized (Tfm) mouse exhibits a nonfunctional androgen receptor and low circulating testosterone concentrations. We used the Tfm mouse to determine whether testosterone modulates atheroma formation via its classic signaling pathway involving the nuclear androgen receptor, conversion to 17␤-estradiol, or an alternative signaling pathway. Methods and Results-Tfm mice (nϭ31) and XY littermates (nϭ8) were separated into 5 experimental groups. Each group received saline (Tfm, nϭ8; XY littermates, nϭ8), physiological testosterone alone (Tfm, nϭ8), physiological testosterone in conjunction with the estrogen receptor ␣ antagonist fulvestrant (Tfm, nϭ8), or physiological testosterone in conjunction with the aromatase inhibitor anastrazole (Tfm, nϭ7). All groups were fed a cholesterol-enriched diet for 28 weeks. Serial sections from the aortic root were examined for fatty streak formation. Blood was collected for measurement of total cholesterol, high-density lipoprotein cholesterol (HDLC), non-HDLC, testosterone, and 17␤-estradiol. Physiological testosterone replacement significantly reduced fatty streak formation in Tfm mice compared with placebo-treated controls (0.37Ϯ0.07% versus 2.86Ϯ0.39%, respectively; PՅ0.0001). HDLC concentrations also were significantly raised in Tfm mice receiving physiological testosterone replacement compared with those receiving placebo (2.81Ϯ0.30 versus 2.08Ϯ0.09 mmol/L, respectively; Pϭ0.05). Cotreatment with either fulvestrant or anastrazole completely abolished the improvement in HDLC. Conclusion-Physiological testosterone replacement inhibited fatty streak formation in the Tfm mouse, an effect that was independent of the androgen receptor. The observed increase in HDLC is consistent with conversion to 17␤-estradiol.