Millimeter wave radiation to measure blood flow in healthy human subjects.

Objective.Peripheral Artery Disease (PAD) is a progressive cardiovascular condition affecting 8-10 million adults in the United States. PAD elevates the risk of cardiovascular events, but up to 50% of people with PAD are asymptomatic and undiagnosed. In this study, we tested the ability of a device, REFLO (Rapid Electromagnetic FLOw), to identify low blood flow using electromagnetic radiation and dynamic thermography toward a non-invasive PAD diagnostic.Approach.During REFLO radio frequency (RF) irradiation, the rate of temperature increase is a function of the rate of energy absorption and blood flow to the irradiated tissue. For a given rate of RF energy absorption, a slow rate of temperature increase implies a large blood flow rate to the tissue. This is due to the cooling effect of the blood. Post-irradiation, a slow rate of temperature decrease is associated with a low rate of blood flow to the tissue. Here, we performed two cohorts of controlled flow experiments on human calves during baseline, occluded, and post-occluded conditions. Nonlinear regression was used to fit temperature data and obtain the rate constant, which was used as a metric for blood flow.Main results.In the pilot study, (N= 7) REFLO distinguished between baseline and post-occlusion during the irradiation phase, and between baseline and occlusion in the post-irradiation phase. In the reliability study, (N= 5 with 3 visits each), two-way ANOVA revealed that flow and subject significantly affected skin heating and cooling rates, while visit did not.Significance.Results suggest that MMW irradiation can be used to distinguish between blood flow rates in humans. Utilizing the rate of skin cooling rather than heating is more consistent for distinguishing flow. Future modifications and clinical testing will aim to improve REFLO's ability to distinguish between flow rates and evaluate its ability to accurately identify PAD.

Virulent Pseudomonas aeruginosa infection converts antimicrobial amyloids into cytotoxic prions.

Pseudomonas aeruginosa infection elicits the production of cytotoxic amyloids from lung endothelium, yet molecular mechanisms of host-pathogen interaction that underlie the amyloid production are not well understood. We examined the importance of type III secretion system (T3SS) effectors in the production of cytotoxic amyloids. P aeruginosa possessing a functional T3SS and effectors induced the production and release of cytotoxic amyloids from lung endothelium, including beta amyloid, and tau. T3SS effector intoxication was sufficient to generate cytotoxic amyloid release, yet intoxication with exoenzyme Y (ExoY) alone or together with exoenzymes S and T (ExoS/T/Y) generated the most virulent amyloids. Infection with lab and clinical strains engendered cytotoxic amyloids that were capable of being propagated in endothelial cell culture and passed to naïve cells, indicative of a prion strain. Conversely, T3SS-incompetent P aeruginosa infection produced non-cytotoxic amyloids with antimicrobial properties. These findings provide evidence that (1) endothelial intoxication with ExoY is sufficient to elicit self-propagating amyloid cytotoxins during infection, (2) pulmonary endothelium contributes to innate immunity by generating antimicrobial amyloids in response to bacterial infection, and (3) ExoY contributes to the virulence arsenal of P aeruginosa through the subversion of endothelial amyloid host-defense to promote a lung endothelial-derived cytotoxic proteinopathy.