Measuring dilution of microbicide gels with optical imaging.

We present a novel approach for measuring topical microbicide gel dilution using optical imaging. The approach compares gel thickness measurements from fluorimetry and multiplexed low coherence interferometry in order to calculate dilution of a gel. As a microbicide gel becomes diluted at fixed thickness, its mLCI thickness measurement remains constant, while the fluorimetry signal decreases in intensity. The difference between the two measurements is related to the extent of gel dilution. These two optical modalities are implemented in a single endoscopic instrument that enables simultaneous data collection. A preliminary validation study was performed with in vitro placebo gel measurements taken in a controlled test socket. It was found that change in slope of the regression line between fluorimetry and mLCI based measurements indicates dilution. A dilution calibration curve was then generated by repeating the test socket measurements with serial dilutions of placebo gel with vaginal fluid simulant. This methodology can provide valuable dilution information on candidate microbicide products, which could substantially enhance our understanding of their in vivo functioning

Error Analysis of dilution calculation derived from the slope of the line of best fit in Figure 3. SD = standard deviation.

<p>Error Analysis of dilution calculation derived from the slope of the line of best fit in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082213#pone-0082213-g003" target="_blank">Figure 3</a>. SD =  standard deviation.</p

Calculated index of refraction values (<i>n</i>) for FACTS-001 gel diluted with vaginal fluid simulant. These values were used for accurate calibration of the mLCI modality.

<p>Calculated index of refraction values (<i>n</i>) for FACTS-001 gel diluted with vaginal fluid simulant. These values were used for accurate calibration of the mLCI modality.</p

Gel thickness measurements of 33% VFS dilution of FACTS-001 gel with vaginal fluid simulant in the calibration socket as measured by fluorimetry (y-axis) and mLCI (x-axis).

<p>A refractive index value of 1.4 (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082213#pone-0082213-t001" target="_blank">Table 1</a>) was used to calculate mLCI thickness. Line of best fit was found using a weighted least-squares algorithm. The 95% confidence interval for the fitted line is provided by the dashed lines.</p

Imaging probe geometry as used with the test socket.

<p>The internal endoscope, which includes both the mLCI and fluorimetry imaging systems, rotates together freely inside the epoxy tube. The mLCI field of view is offset +20-mm in the axial direction and 180-degrees azimuthally. The test socket consists of grooves at five depths, ranging from 36–375 <i>µ</i>m.</p

Line of best fit slope (from weighted total linear regression in Fig. 2) plotted against gel dilution (% VFS).

<p>The sigmoid fit was determined with a logistic 4-parameter analysis, and the resultant equation is displayed in the figure.</p

Activation of inflammatory and pro-thrombotic pathways in acute stress cardiomyopathy.

Stress cardiomyopathy (SCM) is a unique cardiac disorder that more often occurs in women. SCM presents in a similar fashion as acute myocardial infarction (AMI), with chest pain, ECG changes, and congestive heart failure. The primary distinguishing feature is the absence of thrombotic coronary occlusion in SCM. How this reduction in cardiac function occurs in the absence of coronary occlusion remains unknown. Therefore, we tested the hypothesis that a targeted proteomic comparison of patients with acute SCM and AMI might identify relevant mechanistic differences. Blood was drawn in normal controls