Prospective, Randomized, Fellow Eye-Controlled Study of Postoperative Pain and Inflammation Control with an Intracanalicular Dexamethasone 0.4 mg Ophthalmic Insert Following Small Incision Lenticule Extraction.

Purpose: To compare postoperative anterior chamber inflammation, pain, and patient preference following small incision lenticule extraction (SMILE) in eyes treated with a dexamethasone 0.4 mg intracanalicular insert (DEX) or topical prednisolone acetate (PRED). Patients and Methods: In this prospective, randomized, fellow eye-controlled trial, 20 patients underwent same-day, bilateral SMILE. One randomly-selected eye of each patient received DEX placed immediately postoperatively, and the fellow eye received topical PRED tapered over 2 weeks. Postoperative evaluations were performed on day 1, week 1, month 1, and month 3. Primary outcomes included postoperative pain, incidence of anterior chamber cell and flare, and patient preference of steroid therapy. Results: No eyes in either group had any clinically evident cell or flare at any postoperative time point. Mean pain scores (0-10 by subjective report) and incidence of any pain were statistically similar at all postoperative visits. Uncorrected distance visual acuity improved in all eyes, 91% of which achieved 20/25 or better. No eyes lost any lines of corrected distance visual acuity. Three eyes developed a steroid-related rise in intraocular pressure, all of which resolved with 2 of the 3 eyes requiring topical therapy. At 1 week, 1 month, and 3 months, 70%, 65%, and 53% of patients preferred DEX over PRED therapy, respectively. Conclusion: The DEX insert was preferred by more patients and controlled postoperative inflammation and pain comparably to topical PRED in eyes undergoing SMILE. There were no statistically significant differences in visual outcomes between the two groups.

A novel 3D fibril force assay implicates src in tumor cell force generation in collagen networks.

New insight into the biomechanics of cancer cell motility in 3D extracellular matrix (ECM) environments would significantly enhance our understanding of aggressive cancers and help identify new targets for intervention. While several methods for measuring the forces involved in cell-matrix interactions have been developed, previous to this study none have been able to measure forces in a fibrillar environment. We have developed a novel assay for simultaneously measuring cell mechanotransduction and motility in 3D fibrillar environments. The assay consists of a controlled-density fibrillar collagen gel atop a controlled-stiffness polyacrylamide (PAA) surface. Forces generated by living cells and their migration in the 3D collagen gel were measured with the 3D motion of tracer beads within the PAA layer. Here, this 3D fibril force assay is used to study the role of the invasion-associated protein kinase Src in mechanotransduction and motility. Src expression and activation are linked with proliferation, invasion, and metastasis, and have been shown to be required in 2D for invadopodia membranes to direct and mediate invasion. Breast cancer cell line MDA-MD-231 was stably transfected with GFP-tagged constitutively active Src or wild-type Src. In 3D fibrillar collagen matrices we found that, relative to wild-type Src, constitutively active Src: 1) increased the strength of cell-induced forces on the ECM, 2) did not significantly change migration speed, and 3) increased both the duration and the length, but not the number, of long membrane protrusions. Taken together, these results support the hypothesis that Src controls invasion by controlling the ability of the cell to form long lasting cellular protrusions to enable penetration through tissue barriers, in addition to its role in promoting invadopodia matrix-degrading activity.

Autonomous bacterial localization and gene expression based on nearby cell receptor density.

Escherichia coli were genetically modified to enable programmed motility, sensing, and actuation based on the density of features on nearby surfaces. Then, based on calculated feature density, these cells expressed marker proteins to indicate phenotypic response. Specifically, site-specific synthesis of bacterial quorum sensing autoinducer-2 (AI-2) is used to initiate and recruit motile cells. In our model system, we rewired E. coli's AI-2 signaling pathway to direct bacteria to a squamous cancer cell line of head and neck (SCCHN), where they initiate synthesis of a reporter (drug surrogate) based on a threshold density of epidermal growth factor receptor (EGFR). This represents a new type of controller for targeted drug delivery as actuation (synthesis and delivery) depends on a receptor density marking the diseased cell. The ability to survey local surfaces and initiate gene expression based on feature density represents a new area-based switch in synthetic biology that will find use beyond the proposed cancer model here.