Leveraging Preclinical Modeling for Clinical Advancements in Single Ventricle Physiology: Spotlight on the Fontan Circulation.

Preclinical modeling of human circulation has been instrumental in advancing cardiovascular medicine. Alongside clinical research, the armamentarium of computational (e.g.

Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution.

Blood brain barrier-crossing molecules targeting transferrin receptor (TfR) and CD98 heavy chain (CD98hc) are widely reported to promote enhanced brain delivery of therapeutics. Here, we provide a comprehensive and unbiased biodistribution characterization of TfR and CD98hc antibody transport vehicles (ATV and ATV) compared to control IgG. Mouse whole-body tissue clearing reveals distinct organ localization for each molecule.

Design and Validation of a High-Fidelity Left Atrial Cardiac Simulator for the Study and Advancement of Left Atrial Appendage Occlusion.

Purpose: Atrial fibrillation (AF) is the most common chronic cardiac arrhythmia that increases the risk of stroke, primarily due to thrombus formation in the left atrial appendage (LAA). Left atrial appendage occlusion (LAAO) devices offer an alternative to oral anticoagulation for stroke prevention. However, the complex and variable anatomy of the LAA presents significant challenges to device design and deployment.

Effects of a New Enzymatic Debrider (SN514-066b) on Eschar Protein Digestion, Burn Wound Debridement, and Healthy Skin Irritation.

SN514 is a thermolysin-like enzyme under development as a debrider. Preclinical and non-clinical studies supported a first in human healthy volunteer study to predict the need for protection of periwound skin. Pharmacologic activity testing compared digestion of collagen, fibrin, and elastin with relevant enzymes.

Characterizing safety, toxicity, and breast cancer risk reduction using a long-term fulvestrant eluting implant.

For individuals at high risk of developing breast cancer, interventions to mitigate this risk include surgical removal of their breasts and ovaries or five years treatment with the anti-estrogen tamoxifen or aromatase inhibitors. We hypothesized that a silicone based anti-estrogen-eluting implant placed within the breast would provide the risk reduction benefit of hormonal therapy, but without the adverse effects that limit compliance. To this end, we demonstrate that when placed adjacent to mammary tissue in the 7,12-dimethylbenz[a]anthracene-induced rat breast cancer model a fulvestrant-eluting implant delays breast cancer with minimal systemic exposure.