\n\nMethods/design: This study (a prospective, cluster-randomized controlled clinical

trial) will be conducted across selected regions in the state of New South Wales, Australia. Fifty GPs will be randomized to either the ‘intervention’ or ‘control’ arm, with each GP recruiting 10 patients (aged >= 65 with AF); target sample size is 500 patients. GPs in the intervention arm will use CARAT during routine patient consultations to: assess risk factors for stroke, bleeding and medication misadventure; quantify the risk/benefit ratio of antithrombotic treatment, identify the recommended therapy, and decide on the treatment course, for an individual patient. CARAT will be applied by the GP at baseline and repeated at 12 months to identify any changes

to treatment requirements. At baseline, the participant (patients and SBE-β-CD concentration GPs) characteristics will be recorded, as well as relevant practice and clinical parameters. Patient follow up will occur at 1, 6, and 12 months via telephone interview to identify changes to therapy, medication side effects, or clinical events.\n\nDiscussion: This project tests the utility of a novel decision support tool (CARAT) in improving the use of preventative therapy to reduce the significant burden of stroke. Importantly, it targets the interface of patient care (general practice), addresses the at-risk population, evaluates clinical outcomes, and offers a tool that may be sustainable via integration into prescribing software and primary this website care services. GP support and guidance in identifying at risk patients for the appropriate selection of therapy is widely acknowledged. This trial will evaluate the impact of CARAT on the prescription of antithrombotic Belnacasan cost therapy, its longer-term impact on clinical outcomes including stroke and bleeding, and clinicians perceived utility of CARAT in practice.”
“Trypanosoma cruzi infection triggers substantial production of nitric oxide (NO), which has been shown to have protective and toxic effects on the host’s

immune system. Sensing of trypomastigotes by phagocytes activates the inducible NO-synthase (NOS2) pathway, which produces NO and is largely responsible for macrophage-mediated killing of T. cruzi. NO is also responsible for modulating virtually all steps of innate and adaptive immunity. However, NO can also cause oxidative stress, which is especially damaging to the host due to increased tissue damage. The cytokines IFN-gamma and TNF-alpha, as well as chemokines, are strong inducers of NOS2 and are produced in large amounts during T. cruzi acute infection. Conversely, TGF-beta and IL-10 negatively regulate NO production. Here we discuss the recent evidence describing the mechanisms by which NO is able to exert its antimicrobial and immune regulatory effects, the mechanisms involved in the oxidative stress response during infection and the implications of NO for the development of therapeutic strategies against T. cruzi.