Although oral combination antiretroviral therapy effectively clears plasma HIV, patients on oral drugs exhibit much lower drug concentrations in lymph nodes than blood. This drug insufficiency is linked to residual HIV in cells of lymph nodes. While nanoformulations improve drug solubility, safety and delivery, most HIV nanoformulations are intended to extend plasma levels. A stable nanodrug combination that transports, delivers and accumulates in lymph nodes is needed to clear HIV in lymphoid tissues. This review discusses limitations of current oral combination antiretroviral therapy and advances in anti-HIV nanoformulations. A ‘systems approach’ has been proposed to overcome these limitations. This concept has been used to develop nanoformulations for overcoming drug insufficiency, extending cell and tissue exposure and clearing virus for treating HIV/AIDS.

The evaluation of candidate materials and designs for soft tissue scaffolds would benefit from the ability to monitor the mechanical remodeling of the implant site without the need for periodic animal sacrifice and explant analysis. Toward this end, the ability of non-invasive ultrasound elasticity imaging (UEI) to assess temporal mechanical property changes in three different types of porous, biodegradable polyurethane scaffolds was evaluated in a rat abdominal wall repair model. The polymers utilized were salt-leached scaffolds of poly(carbonate urethane) urea, poly(ester urethane) urea and poly(ether ester urethane) urea at 85% porosity. A total of 60 scaffolds (20 each type) were implanted in a full thickness muscle wall replacement in the abdomens of 30 rats. The constructs were ultrasonically scanned every 2 weeks and harvested at weeks 4, 8 and 12 for compression testing or histological analysis. UEI demonstrated different temporal stiffness trends among the different scaffold types, while the stiffness of the surrounding native tissue remained unchanged. The changes in average normalized strains developed in the constructs from UEI compared well with the changes of mean compliance from compression tests and histology. The average normalized strains and the compliance for the same sample exhibited a strong linear relationship. The ability of UEI to identify herniation and to characterize the distribution of local tissue in-growth with high resolution was also investigated. In summary, the reported data indicate that UEI may allow tissue engineers to sequentially evaluate the progress of tissue construct mechanical behavior in vivo and in some cases may reduce the need for interim time point animal sacrifice.

In a previous paper [R. Raspet, et al., J. Acoust. Soc. Am. 119, 834-843 (2006)], a method was introduced to predict upper and lower bounds for wind noise measured in spherical wind-screens from the measured incident velocity spectra. That paper was restricted in that the predictions were only valid within the inertial range of the incident turbulence, and the data were from a measurement not specifically designed to test the predictions. This paper extends the previous predictions into the source region of the atmospheric wind turbulence, and compares the predictions to measurements made with a large range of wind-screen sizes. Predictions for the turbulence-turbulence interaction pressure spectrum as well as the stagnation pressure fluctuation spectrum are calculated from a form fit to the velocity fluctuation spectrum. While the predictions for turbulence-turbulence interaction agree well with measurements made within large (1.0 m) wind-screens, and the stagnation pressure predictions agree well with unscreened gridded microphone measurements, the mean shear-turbulence interaction spectra do not consistently appear in measurements.

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Background: Cancer metastasis has emerged as a major public health threat that causes majority of cancer fatalities. Traditional chemotherapeutics have been effective in the past but suffer from low therapeutic efficiency and harmful side-effects. Recently, it has been reported ursolic acid (UA), one of the naturally abundant pentacyclic triterpenes, possesses a wide range of biological activities including anti-inflammatory, anti-atherosclerotic, and anti-cancer properties. More importantly, UA has the features of low toxicity, liver protection and the potential of anti-cancer metastasis. Objective: This article aimed at reviewing the great potential of UA used as a candidate drug in the field of cancer therapy relating to suppression of tumor initiation, progression and metastasis. Methods: Selective searches were conducted in Pubmed, Google Scholar and Web of Science using the keywords and subheadings from database inception to December 2017. Systemic reviews are summarized here. Results: UA has exhibited chemopreventive and therapeutic effects of cancer mainly through inducing apoptosis, inhibiting cell proliferation, preventing tumor angiogenesis and metastatic. UA nanoformulations could enhance the solubility and bioavailability of UA as well as exhibit better inhibitory effect on tumor growth and metastasis. Conclusion: The information presented in this article can provide useful references for further studies on making UA a promising anti-cancer drug, especially as a prophylactic metastatic agent for clinical applications.

Measurements of the wind noise measured at the ground surface outdoors are analyzed using the mirror flow model of anisotropic turbulence by Kraichnan [J. Acoust. Soc. Am. 28(3), 378-390 (1956)]. Predictions of the resulting behavior of the turbulence spectrum with height are developed, as well as predictions of the turbulence-shear interaction pressure at the surface for different wind velocity profiles and microphone mounting geometries are developed. The theoretical results of the behavior of the velocity spectra with height are compared to measurements to demonstrate the applicability of the mirror flow model to outdoor turbulence. The use of a logarithmic wind velocity profile for analysis is tested using meteorological models for wind velocity profiles under different stability conditions. Next, calculations of the turbulence-shear interaction pressure are compared to flush microphone measurements at the surface and microphone measurements with a foam covering flush with the surface. The measurements underneath the thin layers of foam agree closely with the predictions, indicating that the turbulence-shear interaction pressure is the dominant source of wind noise at the surface. The flush microphones measurements are intermittently larger than the predictions which may indicate other contributions not accounted for by the turbulence-shear interaction pressure.

Medication adherence and insufficient drug levels are central to HIV/AIDS disease progression. Recently, Fletcher et al. confirmed that HIV patients on oral antiretroviral therapy had lower intracellular drug concentrations in lymph nodes than in blood. For instance, in the same patient, multiple lymph node drug concentrations were as much as 99 % lower than in blood. This study built upon our previous finding that HIV patients taking oral indinavir had 3-fold lower mononuclear cell drug concentrations in lymph nodes than in blood. As a result, an association between insufficient lymph node drug concentrations in cells and persistent viral replication has now been validated. Lymph node cells, particularly CD4 T lymphocytes, host HIV infection and persistence; CD4 T cell depletion in blood correlates with AIDS progression. With established drug targets to overcome drug insufficiency in lymphoid cells and tissues, we have developed and employed a “Systems Approach” to engineer multi-drug-incorporated particles for HIV treatment. The goal is to improve lymphatic HIV drug exposure to eliminate HIV drug insufficiency and disease progression. We found that nano-particulate drugs that absorb, transit, and retain in the lymphatic system after subcutaneous dosing improve intracellular lymphatic drug exposure and overcome HIV lymphatic drug insufficiency. The composition, physical properties, and stability of the drug nanoparticles contribute to the prolonged and enhanced drug exposure in lymphoid cells and tissues. In addition to overcoming lymphatic drug insufficiency and potentially reversing HIV infection, targeted drug nanoparticle properties may extend drug concentrations and enable the development of long-acting HIV drug therapy for enhanced patient compliance.

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