N-phenacylthiazolium bromide reduces bone fragility induced by nonenzymatic glycation.

Nonenzymatic glycation (NEG) describes a series of post-translational modifications in the collagenous matrices of human tissues. These modifications, known as advanced glycation end-products (AGEs), result in an altered collagen crosslink profile which impacts the mechanical behavior of their constituent tissues. Bone, which has an organic phase consisting primarily of type I collagen, is significantly affected by NEG. Through constant remodeling by chemical resorption, deposition and mineralization, healthy bone naturally eliminates these impurities. Because bone remodeling slows with age, AGEs accumulate at a greater rate. An inverse correlation between AGE content and material-level properties, particularly in the post-yield region of deformation, has been observed and verified. Interested in reversing the negative effects of NEG, here we evaluate the ability of n-phenacylthiazolium bromide (PTB) to cleave AGE crosslinks in human cancellous bone. Cancellous bone cylinders were obtained from nine male donors, ages nineteen to eighty, and subjected to one of six PTB treatments. Following treatment, each specimen was mechanically tested under physiological conditions to failure and AGEs were quantified by fluorescence. Treatment with PTB showed a significant decrease in AGE content versus control NEG groups as well as a significant rebound in the post-yield material level properties (p<0.05). The data suggest that treatment with PTB could be an effective means to reduce AGE content and decrease bone fragility caused by NEG in human bone

Effects of PTB on Strain Ratio for all age groups is shown in black.

<p>R-ribosylated, X1 & X2 0.015 M PTB for 3 & 7 days, respectively and X3 & X4 0.15 M PTB for 3 & 7 days, respectively. Mean values of Strain Ratio were calculated and then normalized as a percentage of Control value. The dashed line represents control level. For all PTB treatments strain ratio decreased from the ribosylated value, (*P<0.001, **P<0.05).</p

NEG Content for Control (shaded) and Ribosylated (solid black) specimens in Young and Old groups (p<0.05).

<p>NEG Content for Control (shaded) and Ribosylated (solid black) specimens in Young and Old groups (p<0.05).</p

Effects of PTB on the Post-Yield Strain for all age groups is shown in black.

<p>R-ribosylated, X1 & X2 0.015 M PTB for 3 & 7 days, respectively and X3 & X4 0.15 M PTB for 3 & 7 days, respectively. Mean values of Post-Yield Strain were calculated and then normalized as a percentage of Control value. The dashed line represents control level. For all PTB treatments post-yield strain increased from the ribosylated value, (P<0.01).</p

NEG content for Young (shaded) vs. Old (solid black) for all treatment groups C-control, R-ribosylated, X1 & X2 0.015 M PTB for 3 & 7 days, respectively and X3 & X4 0.15 M PTB for 3 & 7 days, respectively.

<p>NEG content for Young (shaded) vs. Old (solid black) for all treatment groups C-control, R-ribosylated, X1 & X2 0.015 M PTB for 3 & 7 days, respectively and X3 & X4 0.15 M PTB for 3 & 7 days, respectively.</p

Outline of Control and Treatment Groups.

<p>Outline of Control and Treatment Groups.</p

Strain Ratio values of all donors are shown for Control specimens (solid black) against Ribosylated (grey) specimens.

<p>For all donors, strain ratio was significantly increased (P<0.05) after glycation.</p

Post Yield Strain values of all donors are shown for Control specimens (solid black) against Ribosylated (grey) specimens.

<p>For all donors, post yield strain was significantly reduced (P<0.01).</p

Photoplethysmography behind the Ear Outperforms Electrocardiogram for Cardiovascular Monitoring in Dynamic Environments

An increasing proportion of occupational mishaps in dynamic, high-risk operational environments have been attributed to human error, yet there are currently no devices to routinely provide accurate physiological data for insights into underlying contributing factors. This is most commonly due to limitations of commercial and clinical devices for collecting physiological data in environments of high motion. Herein, a novel Photoplethysmography (PPG) sensor device was tested, called SPYDR (Standalone Performance Yielding Deliberate Risk), reading from a behind-the-ear location, specifically designed for high-fidelity data collection in highly dynamic high-motion, high-pressure, low-oxygen, and high-G-force environments. For this study, SPYDR was installed as a functional ear-cup replacement in flight helmets worn by rated US Navy aircrew. Subjects were exposed to reduced atmospheric pressure using a hypobaric chamber to simulated altitudes of 25,000 feet and high G-forces in a human-rated centrifuge up to 9 G acceleration. Data were compared to control devices, finger and forehead PPG sensors, and a chest-mounted 12-lead ECG. SPYDR produced high-fidelity data compared to controls with little motion-artifact controls in the no-motion environment of the hypobaric chamber. However, in the high-motion, high-force environment of the centrifuge, SPYDR recorded consistent, accurate data, whereas PPG controls and ECG data were unusable due to a high-degree-motion artifacts. The data demonstrate that SPYDR provides an accurate and reliable system for continuous physiological monitoring in high-motion, high-risk environments, yielding a novel method for collecting low-artifact cardiovascular assessment data important for investigating currently inaccessible parameters of human physiology