Development and Pilot Feasibility Study of a Health Information Technology Tool to Calculate Mortality Risk for Patients with Asymptomatic Carotid Stenosis: The Carotid Risk Assessment Tool (CARAT)

Patients with no history of stroke but with stenosis of the carotid arteries can reduce the risk of future stroke with surgery or stenting. At present, a physicians’ ability to recommend optimal treatments based on an individual’s risk profile requires estimating the likelihood that a patient will have a poor peri-operative outcomes and the likelihood that the patient will survive long enough to gain benefit from the procedure. We describe the development of the CArotid Risk Assessment Tool (CARAT) into a 2-year mortality risk calculator within the electronic medical record, integrating the tool into the clinical workflow, training the clinical team to use the tool, and assessing the feasibility and acceptability of the tool in one clinic setting

Soluble extract from the nematode Strongyloides stercoralis induces CXCR2 dependent/IL-17 independent neutrophil recruitment.

Neutrophil recruitment via CXCR2 is required for innate and adaptive protective immunity to the larvae of Strongyloides stercoralis in mice. The goal of the present study was to determine the mechanism of CXCR2-mediated neutrophil recruitment to S. stercoralis. Mice deficient in the receptor for IL-17A and IL-17F, upstream mediators of CXCR2 ligand production, were infected with S. stercoralis larvae; there was no difference in larval survival, neutrophil recruitment, or production of CXCR2 ligands compared with wild type mice. In vivo and in vitro stimulation of neutrophils with S. stercoralis soluble extract resulted in significant neutrophil recruitment. In vitro assays demonstrated that the recruitment functioned through both chemokinesis and chemotaxis, was specific for CXCR2, and was a G protein-coupled response involving tyrosine kinase and PI3K. Finally, neutrophil stimulation with S. stercoralis soluble extract induced release of the CXCR2 ligands MIP-2 and KC from neutrophils, thereby potentially enhancing neutrophil recruitment

Neutrophils and macrophages in the immune response to parasitic helminths

Neutrophils and macrophages are complex components of the immune system, functioning both as effector killing cells and as initiators and modulators of the development of protective immunity. It was hypothesized that the function and regulation of neutrophils and macrophages is tightly coupled to the ability to defend against parasitic helminths. Using a mouse model of nematode infection, it is determined that neutrophil recruitment to Strongyloides stercoralis occurs directly in response to parasite extract in a manner that is dependent on CXCR2. IL-17R signaling was required neither for neutrophil recruitment nor for the development of host immunity in this model. The ability of neutrophils to kill S. stercoralis was found to be dependent on myeloperoxidase, and mice deficient in myeloperoxidase were unable to mount effective primary or secondary immune responses. Furthermore, the larvicidal activity of neutrophils against S. stercoralis was not an involuntary response, as naïve neutrophils were unable to precipitate larval death in vitro unless macrophages were also in the larval microenvironment. Macrophage regulation was also shown to be important in a model of cestode infection, as IL-4-/- mice succumbed to Mesocestoides corti infection, having decreased numbers of macrophages at the site of infection and decreased expression of alternatively activated macrophage markers. In both of these helminth infection models, host immunity was shown to be dependent on the development of neutrophil and macrophage populations at the site of infection and on the apposite functioning of these cells. In conclusion, the appropriate activity and regulation of neutrophils and macrophages is an important determinant of immunity to helminth parasites

Characterization and fabrication tools for emerging nanobionics

The interfacing of technology and living cells in the nanoscale domain -nanobionics- is being enabled by scanning probe tools, including Bio-Atomic Force Microscopy and Dip Pen Nanolithography, providing a nanoscale insight into the cell-material interface and an unprecedented approach to nanofabrication

Practical Murine Hematopathology: A Comparative Review and Implications for Research

Hematologic parameters are important markers of disease in human and veterinary medicine. Biomedical research has benefited from mouse models that recapitulate such disease, thus expanding knowledge of pathogenetic mechanisms and investigative therapies that translate across species. Mice in health have many notable hematologic differences from humans and other veterinary species, including smaller erythrocytes, higher percentage of circulating reticulocytes or polychromasia, lower peripheral blood neutrophil and higher peripheral blood and bone marrow lymphocyte percentages, variable leukocyte morphologies, physiologic splenic hematopoiesis and iron storage, and more numerous and shorter-lived erythrocytes and platelets. For accurate and complete hematologic analyses of disease and response to investigative therapeutic interventions, these differences and the unique features of murine hematopathology must be understood. Here we review murine hematology and hematopathology for practical application to translational investigation