Physiochemical Characterization of Lipidic Nanoformulations Encapsulating the Antifungal Drug Natamycin.

Natamycin is a tetraene polyene that exploits its antifungal properties by irreversibly binding components of fungal cell walls, blocking the growth of infections. However, topical ocular treatments with natamycin require frequent application due to the low ability of this molecule to permeate the ocular membrane. This limitation has limited the use of natamycin as an antimycotic drug, despite it being one of the most powerful known antimycotic agents. In this work, different lipidic nanoformulations consisting of transethosomes or lipid nanoparticles containing natamycin are proposed as carriers for optical topical administration. Size, stability and zeta potential were characterized via dynamic light scattering, the supramolecular structure was investigated via small- and wide-angle X-ray scattering and 1H-NMR, and the encapsulation efficiencies of the four proposed formulations were determined via HPLC-DAD.

The effect of cleat position on foot pain in cyclists.

Amateur or non-competitive cycling is one of the most popular and growing sports, and the repetitive nature of this sport, combined with a cleat position that is too far forward, often leads to peripheral ischemia or pressure, which can cause pain at the metatarsal level due to the nerve and vascular structures present at this level, according to several authors. This clinical series describes the work done to reduce pain in 21 cyclists who reported foot pain/discomfort exclusively during pedaling. To exclude different causes of pain, other than the position of the cleat, the cyclists received biomechanical assessments using an indoor bike smart trainer and a 2D motion capture system. The pain was found to be associated with the incorrect positioning of the shoe cleats, which were generally positioned at the level of the phalanges and, according to our hypothesis, in a significantly forward position. Our intervention was to move the cleat back under the metatarsal head in all the cyclists examined. After five cycling sessions, feedback showed significant improvements. The authors were aware of some limitations, such as the small number of subjects studied, the different types of cleats used by different cyclists, and the lack of information on cadence. However, the overall data collected during the study showed a significant improvement of 5 points on the Numeric Pain Rating Scale (NPRS) after treatment. This clinical series supports the hypothesis that cleat retraction improves foot pain in cyclists, but further studies are needed to better characterize and understand the mechanism underlying the development of pain. More methodologically sound studies are needed. The current clinical series is the first of its kind to describe an initial method of reducing metatarsal pain in cyclists.

InCliniGene enables high-throughput and comprehensive in vivo clonal tracking toward clinical genomics data integration.

High-throughput clonal tracking in patients under hematopoietic stem cell gene therapy with integrating vector is instrumental in assessing bio-safety and efficacy. Monitoring the fate of millions of transplanted clones and their progeny across differentiation and proliferation over time leverages the identification of the vector integration sites, used as surrogates of clonal identity. Although γ-tracking retroviral insertion sites (γ-TRIS) is the state-of-the-art algorithm for clonal identification, the computational drawbacks in the tracking algorithm, based on a combinatorial all-versus-all strategy, limit its use in clinical studies with several thousands of samples per patient. We developed the first clonal tracking graph database, InCliniGene (https://github.com/calabrialab/InCliniGene), that imports the output files of γ-TRIS and generates the graph of clones (nodes) connected by arches if two nodes share common genomic features as defined by the γ-TRIS rules. Embedding both clonal data and their connections in the graph, InCliniGene can track all clones longitudinally over samples through data queries that fully explore the graph. This approach resulted in being highly accurate and scalable. We validated InCliniGene using an in vitro dataset, specifically designed to mimic clinical cases, and tested the accuracy and precision. InCliniGene allows extensive use of γ-TRIS in large gene therapy clinical applications and naturally realizes the full data integration of molecular and genomics data, clinical and treatment measurements and genomic annotations. Further extensions of InCliniGene with data federation and with application programming interface will support data mining toward precision, personalized and predictive medicine in gene therapy. Database URL:  https://github.com/calabrialab/InCliniGene.