Conventional and Tropism-Modified High-Capacity Adenoviral Vectors Exhibit Similar Transduction Profiles in Human iPSC-Derived Retinal Organoids.

Viral vector delivery of gene therapy represents a promising approach for the treatment of numerous retinal diseases. Adeno-associated viral vectors (AAV) constitute the primary gene delivery platform; however, their limited cargo capacity restricts the delivery of several clinically relevant retinal genes. In this study, we explore the feasibility of employing high-capacity adenoviral vectors (HC-AdVs) as alternative delivery vehicles, which, with a capacity of up to 36 kb, can potentially accommodate all known retinal gene coding sequences.

Legal Recreational Cannabis Sales and Opioid-Related Mortality in the 5 Years Following Cannabis Legalization in Canada: A Granger Causality Analysis.

Objective: Little is known about the population-level impact of recreational cannabis legalization on trends in opioid-related mortality. Increased access to cannabis due to legalization has been hypothesized to reduce opioid-related deaths because of the potential opioid-sparing effects of cannabis. The objective of this study was to examine the relations between national retail sales of recreational (non-medical) cannabis and opioid overdose deaths in the 5 years following legalization in Canada.

Evaluating the impact of Canadian cannabis legalization on cannabis use outcomes in emerging adults: Comparisons to a US control sample via a natural experiment.

Background: Recreational cannabis legalization marked a significant policy shift in Canada, but has been difficult to evaluate because of the absence of a control group. Although it is unfeasible to evaluate legalization using a randomized controlled trial design, sophisticated statistical techniques can employ quasi-experimental designs using natural experiments. This study evaluates the impact of cannabis legalization in a longitudinal cohort of Canadian emerging adults by comparing changes in cannabis use frequency and related consequences over time to changes in a similar cohort in a United States jurisdiction where no policy change took place.

Enzymatic epimerization of monoterpene indole alkaloids in Kratom.

Monoterpene indole alkaloids (MIAs) are a large, structurally diverse class of bioactive natural products. These compounds are biosynthetically derived from a stereoselective Pictet-Spengler condensation that generates a tetrahydro-β-carboline scaffold characterized by a 3 stereocenter. However, a subset of MIAs contain a non-canonical 3 stereocenter.

High-Valent Cobalt-Difluoride in Oxidative Fluorination of Saturated Hydrocarbons.

The heme paradigm where Fe=O acts as the C-H oxidant and Fe-OH rebounds with the formed carbon-centered radical guides the design of the prototypical synthetic hydroxylation catalyst. We are exploring methods to evolve beyond the metal-oxo oxidant and hydroxide rebound, to incorporate a wider array of functional group. We have demonstrated the application of Co(OTf) (10 mol% catalyst; OTf=trimfluoromethanesulfonate) in combination with polydentate N-donor ligands (e.