Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models

Mohammadi, S., Jones, L., & Gorbet, M. (2014). Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models. PLoS ONE, 9(9), e106653. https://doi.org/10.1371/journal.pone.0106653In this study, we compared, for the first time, the release of a 432 kDa prostaglandin analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ( solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6 of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 , was released, (). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.The funding for this project was provided by a Collaborative Health Research Project grant (jointly funded by NSERC and CIHR)

A Constitutive Model for Entangled Polydisperse Linear Flexible Polymers with Entanglement Dynamics and a Configuration Dependent Friction Coefficient. Part I: Model Derivation

A new polydisperse toy constitutive model is derived and developed from fundamental principles and ideas governing the nonlinear rheology of linear flexible polymers [Mead et al., J. Rheol. 59, 335-363 (2015)]. Specifically, the new model is comprised of four fundamental pieces. First, the model contains a simple differential description of the entanglement dynamics of discrete entanglement pairs. Second, the model contains a differential description of the ij entanglement pair orientation tensor dynamics. Third, following a similar development by Mead and Mishler [J. Non-Newtonian Fluid Mech. 197, 61-79 and 80-90 (2013).], a diluted stretch tube is constructed to describe the relative stretch of each component in the molecular weight distribution (MWD). Fourth, a description of configuration dependent friction coefficients is generated by generalizing the monodisperse formulation of Ianniruberto et al. [Macromolecules 45, 8058-8066 (2012)]. The polydisperse stress calculator is developed from the orientation, stretch and entanglement density and is fundamentally different from other molecular models that assume a constant entanglement density. The resulting model is comprised of three differential evolution equations and is simple to code and fast to execute. The model can simulate arbitrary fast nonlinear flows of arbitrary MWD\u27s. In the slow flow linear viscoelastic limit, the model collapses to the double reptation model. This welcome result has positive implications with respect to our model parameter determination [Ye et al., J. Rheol. 47, 443-468 (2003); Ye and Sridhar, Macromolecules 38, 3442-3449 (2005)] for making quantitative calculations

Shaking Table Methodology and Instrumentation for Reinforced Soil Retaining Walls

The paper describes a testing methodology, instrumentation array and example data interpretation for reduced-scale geosynthetic reinforced soil (GRS) wall models built on a large shaking table. The testing program is unique in the literature because of the large number of different instruments deployed and the use of Particle Image Velocimetry (PIV) analysis of imagery captured using a high speed camera. The models are instrumented with strain gauges and extensometers attached to the geogrid reinforcing layers, LVDTs attached to the facing panel, load cells at the wall toe, reinforcement-facing load measurement, and accelerometers in the backfill and along the facing. Example measurements are reported that demonstrate the value of the experimental technique to better understand the mechanics of these systems under simulated earthquake

A Report on the Environmental Impact of the Texas LoanSTAR Program from May 1989 to September 1995

There are a number of factors that influence emission factors. The three major pollutants considered in this analysis are CO2, SO2, and NOX. Emission factors from three different sources were considered for this report. This analysis shows that as of September, 1995, there has been a reduction in emissions of 1.88 million pounds of NOX, 1.19 million pounds of SO2, and 532 million pounds of CO2 through the implementation of energy conservation measures in the Texas LoanSTAR program.The Texas LoanSTAR (Loans to Save Taxes and Resources) program was created by the state of Texas in 1989 to lend money for energy conserving improvements, or retrofits, in public buildings. As of September 1995 the LoanSTAR program is measuring savings for 22 loan sites covering 153 buildings where retrofits have been fully or partially completed. The completed retrofits show $21.1 million in measured savings, which is more than 119% of the energy savings predicted by the energy auditors. This corresponds to 23.9% of the pre-retrofit consumption cost at these sites. Through energy savings, the Texas LoanSTAR program has made a significant contribution towards reducing hazardous environmental emissions

Overview of the Rebuild America Program in Texas

The Rebuild America program is a multi-year program, through the U.S. Department of Energy (USDOE), that will increase investment in energy efficiency. As the program progresses, it will save energy, create jobs, and improve the environment. The Brazos Valley Energy Conservation Coalition (BVECC), administered by the Energy Systems Laboratory (ESL) of Texas A&M University, in College Station, Texas received notification of the US. Department of Energy (USDOE)-Rebuild America award in June, 1996. In the first year of this partnership, the BVECC has developed three Rebuild America related projects in Texas totaling more than $3 million in construction costs. The energy conservation retrofits in the three projects include a lighting upgrade, HVAC systems modifications, and an EMCS upgrade/installation. These projects have been financed through internal facility funding or through third party financing institutes. The average payback period of the retrofit projects is eight years. This paper presents an overview of the BVECC Rebuild America program in Texas. It also describes the energy conservation projects in three facilities in Texas where energy conservation retrofits are being implemented

A Direct Demonstration of Closed-State Inactivation of K+ Channels at Low pH

Lowering external pH reduces peak current and enhances current decay in Kv and Shaker-IR channels. Using voltage-clamp fluorimetry we directly determined the fate of Shaker-IR channels at low pH by measuring fluorescence emission from tetramethylrhodamine-5-maleimide attached to substituted cysteine residues in the voltage sensor domain (M356C to R362C) or S5-P linker (S424C). One aspect of the distal S3-S4 linker α-helix (A359C and R362C) reported a pH-induced acceleration of the slow phase of fluorescence quenching that represents P/C-type inactivation, but neither site reported a change in the total charge movement at low pH. Shaker S424C fluorescence demonstrated slow unquenching that also reflects channel inactivation and this too was accelerated at low pH. In addition, however, acidic pH caused a reversible loss of the fluorescence signal (pKa = 5.1) that paralleled the reduction of peak current amplitude (pKa = 5.2). Protons decreased single channel open probability, suggesting that the loss of fluorescence at low pH reflects a decreased channel availability that is responsible for the reduced macroscopic conductance. Inhibition of inactivation in Shaker S424C (by raising external K+ or the mutation T449V) prevented fluorescence loss at low pH, and the fluorescence report from closed Shaker ILT S424C channels implied that protons stabilized a W434F-like inactivated state. Furthermore, acidic pH changed the fluorescence amplitude (pKa = 5.9) in channels held continuously at −80 mV. This suggests that low pH stabilizes closed-inactivated states. Thus, fluorescence experiments suggest the major mechanism of pH-induced peak current reduction is inactivation of channels from closed states from which they can activate, but not open; this occurs in addition to acceleration of P/C-type inactivation from the open state

Global burden of maternal and congenital syphilis in 2008 and 2012: a health systems modelling study

Background: In 2007, WHO launched a global initiative for the elimination of mother-to-child transmission of syphilis (congenital syphilis). An important aspect of the initiative is strengthening surveillance to monitor progress towards elimination. In 2008, using a health systems model with country data inputs, WHO estimated that 1·4 million maternal syphilis infections caused 520 000 adverse pregnancy outcomes. To assess progress, we updated the 2008 estimates and estimated the 2012 global prevalence and cases of maternal and congenital syphilis. Methods: We used a health systems model approved by the Child Health Epidemiology Reference Group. WHO and UN databases provided inputs on livebirths, antenatal care coverage, and syphilis testing, seropositivity, and treatment in antenatal care. For 2012 estimates, we used data collected between 2009 and 2012. We updated the 2008 estimates using data collected between 2000 and 2008, compared these with 2012 estimates using data collected between 2009 and 2012, and performed subanalyses to validate results. Findings: In 2012, an estimated 930 000 maternal syphilis infections caused 350 000 adverse pregnancy outcomes including 143 000 early fetal deaths and stillbirths, 62 000 neonatal deaths, 44 000 preterm or low weight births, and 102 000 infected infants worldwide. Nearly 80% of adverse outcomes (274 000) occurred in women who received antenatal care at least once. Comparing the updated 2008 estimates with the 2012 estimates, maternal syphilis decreased by 38% (from 1 488 394 cases in 2008 to 927 936 cases in 2012) and congenital syphilis decreased by 39% (from 576 784 to 350 915). India represented 65% of the decrease. Analysis excluding India still showed an 18% decrease in maternal and congenital cases of syphilis worldwide. Interpretation: Maternal and congenital syphilis decreased worldwide from 2008 to 2012, which suggests progress towards the elimination of mother-to-child transmission of syphilis. Nonetheless, maternal syphilis caused substantial adverse pregnancy outcomes, even in women receiving antenatal care. Improved access to quality antenatal care, including syphilis testing and treatment, and robust data are all important for achieving the elimination of mother-to child transmission of syphilis. Funding: The UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction in WHO, and the US Centers for Disease Control and Prevention

Relations Between Depressive Symptoms, Anxiety, and T Wave Abnormalities in Subjects Without Clinically-Apparent Cardiovascular Disease (from the Multi-Ethnic Study of Atherosclerosis [MESA])

The aim of this study was to test the hypothesis that depression and anxiety are associated with electrocardiographic (ECG) repolarization abnormalities in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort free of symptomatic cardiovascular disease. Depressive symptoms were assessed by using the Center for Epidemiologic Studies Depression Scale and trait anxiety symptoms by using the Spielberger State-Trait Anxiety Inventory; both were categorized according to uppermost quartile. T-wave inversions in ECG leads other than V1 to V3 were obtained from electrocardiograms obtained at rest during the baseline examination. Participants with major intraventricular conduction abnormalities and those taking antiarrhythmics, antidepressants, and/or antipsychotics were excluded. Logistic regression models were estimated with multivariable adjustment for traditional cardiovascular disease risk factors. Among 5,906 participants, elevated depressive symptoms were associated with increased odds of T-wave inversion after multivariable adjustment (odds ratio 2.02, 95% confidence interval 1.33 to 3.06, p = 0.001), whereas greater trait anxiety was associated with reduced odds of T-wave inversion (odds ratio 0.47, 95% confidence interval 0.29 to 0.77, p = 0.003). The divergent associations of depressive symptoms and trait anxiety with ECG T-wave inversions were similar in men and women, and these associations were present across the racial and ethnic subgroups (non-Hispanic white, African-American, Hispanic, and Chinese). In conclusion, symptoms of depression and anxiety were independently yet oppositely associated with ECG T-wave inversions. Negative emotions may have a differential impact on cardiovascular mortality through unique relations with cardiac repolarization