Non-Viral Gene Delivery to Hepatocellular Carcinoma via Intra-Arterial Injection.

Purpose: Hepatocellular carcinoma (HCC) has limited treatment options, and modest survival after systemic chemotherapy or procedures such as transarterial chemoembolization (TACE). There is therefore a need to develop targeted therapies to address HCC. Gene therapies hold immense promise in treating a variety of diseases, including HCC, though delivery remains a critical hurdle.

Acute Visual Disturbances and Ataxia Secondary to Attempted COVID-19 Prophylaxis With Ivermectin in a Nine-Year-Old.

Ivermectin is an antiparasitic agent listed as an essential medication by the World Health Organization. Ivermectin utilization has increased due to the popular, though inaccurate, perception of its use in COVID-19 management. Poison Control Central calls regarding ivermectin toxicity have increased 245% since pre-pandemic baselines.

Script Concordance Tests for Formative Clinical Reasoning and Problem-Solving Assessment in General Pediatrics.

Introduction: Script Concordance Tests (SCTs) are short clinical vignettes with proposed diagnoses, diagnostic studies, treatments, and management options for patient care scenarios. The SCTs included in this resource were incorporated into a required pediatric clerkship to facilitate formative student feedback and additional opportunities for precepting faculty to provide midclerkship feedback. Pediatric cases were specifically selected due to the scarcity of medical student experience with common pediatric clinical presentations.

Polymeric nanoparticles for dual-targeted theranostic gene delivery to hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) develops predominantly in the inflammatory environment of a cirrhotic liver caused by hepatitis, toxin exposure, or chronic liver disease. A targeted therapeutic approach is required to enable cancer killing without causing toxicity and liver failure. Poly(beta-amino-ester) (PBAE) nanoparticles (NPs) were used to deliver a completely CpG-free plasmid harboring mutant herpes simplex virus type 1 sr39 thymidine kinase (sr39) DNA to human HCC cells.

Poly(beta-amino ester) nanoparticles enable tumor-specific TRAIL secretion and a bystander effect to treat liver cancer.

Despite initial promise, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based approaches to cancer treatment have yet to yield a clinically approved therapy, due to delivery challenges, a lack of potency, and drug resistance. To address these challenges, we have developed poly(beta-amino ester) (PBAE) nanoparticles (NPs), as well as an engineered cDNA sequence encoding a secretable TRAIL (sTRAIL) protein, to enable reprogramming of liver cancer cells to locally secrete TRAIL protein. We show that sTRAIL initiates apoptosis in transfected cells and has a bystander effect to non-transfected cells.