An Experimental Model Exhibiting Anterograde and Retrograde Vascular Occlusion of Facial Fillers to Avoid Vision Loss.

Background: Facial filler injection techniques that help decrease the risk of vascular occlusion are an important growing area of study. This study demonstrates a model of injecting fillers into a simulated bifurcated arterial system, using different sized needle gauges at a constant injection pressure. Methods: Three facial fillers were injected into a bifurcated intravenous tubing with continuous irrigation at a constant pressure to simulate a vascular system. Videography was used to observe for retrograde flow through the simulated supratrochlear artery to the bifurcation point, where the filler was redirected by anterograde flow into the branch representing the ophthalmic artery. Results: Filler injection with retrograde flow to the bifurcation occurred with all the 27G needle trials. In comparison, the 30G needle trials were only able to reach the bifurcation point in three of the nine trials. The average time to the bifurcation point with subsequent ophthalmic artery anterograde flow with the 27G and 30G needles were 8.44 (95% confidence interval ±2.06) and 33.33 (95% confidence interval ±16.56) seconds, respectively. Conclusions: Larger 27G needles consistently reached retrograde flow and the bifurcation point faster than 30G needles. This study suggests thinner needles may be less likely to cause retrograde occlusion.

Relationship between 2-Hour Tacrolimus Concentrations and Clinical Outcomes in Long Term Kidney Transplantation.

Background: Tacrolimus is routinely monitored using trough concentrations, however, recent data have suggested that area under the curve (AUC) provides better correlation with toxicity and efficacy. Area under the curve is cumbersome to measure, but studies have demonstrated that surrogate time points such as 2-hour concentrations are well correlated with AUC. Methods: This is a single center, retrospective study of adult kidney transplant recipients with 2-hour tacrolimus concentrations measured over three years post-transplant. The primary outcome was to determine the difference in serum creatinine (Scr) in those with 2-hour tacrolimus concentrations greater than 20 ng/mL versus those less than or equal to 20 ng/mL. Results: A total of 150 kidney transplant recipients were included. The mean Scr and glomerular filtration rate were 1.49 ± 1.01 mg/dL and 59 ± 23.2 ml/min/1.73 m2, respectively, for the entire cohort. The rate of donor specific antibody formation was 2% and 8% experienced biopsy-proven rejection. The rate of cytomegalovirus viremia was 2% and BK viremia was 13%. There was no significant difference in kidney function over 36 months for the groups specified a priori. Conclusions: Long-term outcomes of maintaining tacrolimus 2-hour concentrations over 20 ng/mL is favorable with minimal opportunistic infections.

Employing a biochemical protecting group for a sustainable indigo dyeing strategy.

Indigo is an ancient dye uniquely capable of producing the signature tones in blue denim; however, the dyeing process requires chemical steps that are environmentally damaging. We describe a sustainable dyeing strategy that not only circumvents the use of toxic reagents for indigo chemical synthesis but also removes the need for a reducing agent for dye solubilization. This strategy utilizes a glucose moiety as a biochemical protecting group to stabilize the reactive indigo precursor indoxyl to form indican, preventing spontaneous oxidation to crystalline indigo during microbial fermentation. Application of a ß-glucosidase removes the protecting group from indican, resulting in indigo crystal formation in the cotton fibers. We identified the gene coding for the glucosyltransferase PtUGT1 from the indigo plant Polygonum tinctorium and solved the structure of PtUGT1. Heterologous expression of PtUGT1 in Escherichia coli supported high indican conversion, and biosynthesized indican was used to dye cotton swatches and a garment.

Design and Construction of Generalizable RNA-Protein Hybrid Controllers by Level-Matched Genetic Signal Amplification.

For synthetic biology applications, protein-based transcriptional genetic controllers are limited in terms of orthogonality, modularity, and portability. Although ribozyme-based switches can address these issues, their current two-stage architectures and limited dynamic range hinder their broader incorporation into systems-level genetic controllers. Here, we address these challenges by implementing an RNA-protein hybrid controller with a three-stage architecture that introduces a transcription-based amplifier between an RNA sensor and a protein actuator. To facilitate the construction of these more complex circuits, we use a model-guided strategy to efficiently match the activities of stages. The presence of the amplifier enabled the three-stage controller to have up to 200-fold higher gene expression than its two-stage counterpart and made it possible to implement higher-order controllers, such as multilayer Boolean logic and feedback systems. The modularity inherent in the three-stage architecture along with the sensing flexibility of RNA devices presents a generalizable framework for designing and building sophisticated genetic control systems.

Preparing amorphous hydrophobic drug nanoparticles by nanoporous membrane extrusion.

AIM: The aim of the present study was to develop a simple and straightforward method for formulating hydrophobic drugs into nanoparticulate form in a scalable and inexpensive manner. MATERIALS & METHODS: The nanoporous membrane extrusion (NME) method was used to prepare hydrophobic drug nanoparticles. NME is based on the induced precipitation of drug-loaded nanoparticles at the exits of nanopores. Three common hydrophobic drug models (silymarin, ß-carotene and butylated hydroxytoluene) were tested. The authors carefully investigated the morphology, crystallinity and dissolution profile of the resulting nanoparticles. RESULTS: Using NME, the authors successfully prepared rather uniform drug nanoparticles (∼100 nm in diameter). These nanoparticles were amorphous and show an improved dissolution profile compared with untreated drug powders. CONCLUSION: These studies suggest that NME could be used as a general method to produce nanoparticles of hydrophobic drugs.

Preparation of mineralized nanofibers: collagen fibrils containing calcium phosphate.

We report a straightforward, bottom-up, scalable process for preparing mineralized nanofibers. Our procedure is based on flowing feed solution, containing both inorganic cations and polymeric molecules, through a nanoporous membrane into a receiver solution with anions, which leads to the formation of mineralized nanofibers at the exit of the pores. With this strategy, we were able to achieve size control of the nanofiber diameters. We illustrate this approach by producing collagen fibrils with calcium phosphate incorporated inside the fibrils. This structure, which resembles the basic constituent of bones, assembles itself without the addition of noncollagenous proteins or their polymeric substitutes. Rheological experiments demonstrated that the stiffness of gels derived from these fibrils is enhanced by mineralization. Growth experiments of human adipose derived stem cells on these gels showed the compatibility of the fibrils in a tissue-regeneration context.