Trends in cannabis use in New Jersey: Effects of COVID‐19 and cannabis legalization

Abstract Objectives With the legalization of cannabis in New Jersey on April 21, 2022, including the licensing of cannabis dispensaries, concerns have arisen about potential adverse events related to cannabis use. Here, we explore temporal trends and risk factors for cannabis‐related harm in both adult and pediatric cannabis‐related visits at a tertiary care academic institution. Methods We performed a retrospective chart review and temporal trend analysis via the electronic health record from May 1, 2019 to October 31, 2022, covering 2 years before, and 6 months after, cannabis legalization in New Jersey. The pediatric charts identified were analyzed for root causes of adverse events, and changes in the frequency of specific unsafe practices since cannabis legalization were tracked. Results We found that adult cannabis ED‐related visits significantly increased during the COVID‐19 pandemic and remained higher than pre‐pandemic levels for the remainder of the study periods, without a significant change upon legalization. Pediatric rates of cannabis‐related ED visits did not vary significantly during the study period. The vast majority of visits for children aged 0–12 years were related to accidental cannabis exposures—often a household member's edibles—whereas most visits for older children stemmed from intentional cannabis use. Conclusion This project highlights the unintended consequences of wider cannabis access in New Jersey. Notably, cannabis use increased even before its legalization, presumably in response to the COVID‐19 pandemic and its attendant mental health effects. Rates of cannabis use disorder and its highlight of other concurrent psychiatric disorders are important topics for both clinicians and lawmakers to consider

Inhibition by stabilization: Targeting the Plasmodium falciparum aldolase-TRAP complex

Background: Emerging resistance of the malaria parasite Plasmodium to current therapies underscores the critical importance of exploring novel strategies for disease eradication. Plasmodium species are obligate intracellular protozoan parasites. They rely on an unusual form of substrate-dependent motility for their migration on and across host-cell membranes and for host cell invasion. This peculiar motility mechanism is driven by the 'glideosome', an actin-myosin associated, macromolecular complex anchored to the inner membrane complex of the parasite. Myosin A, actin, aldolase, and thrombospondin-related anonymous protein (TRAP) constitute the molecular core of the glideosome in the sporozoite, the mosquito stage that brings the infection into mammals. Methods: Virtual library screening of a large compound library against the PfAldolase-TRAP complex was used to identify candidate compounds that stabilize and prevent the disassembly of the glideosome. The mechanism of these compounds was confirmed by biochemical, biophysical and parasitological methods. Results: A novel inhibitory effect on the parasite was achieved by stabilizing a protein-protein interaction within the glideosome components. Compound 24 disrupts the gliding and invasive capabilities of Plasmodium parasites in in vitro parasite assays. A high-resolution, ternary X-ray crystal structure of PfAldolase-TRAP in complex with compound 24 confirms the mode of interaction and serves as a platform for future ligand optimization. Conclusion: This proof-of-concept study presents a novel approach to anti-malarial drug discovery and design. By strengthening a protein-protein interaction within the parasite, an avenue towards inhibiting a previously "undruggable" target is revealed and the motility motor responsible for successful invasion of host cells is rendered inactive. This study provides new insights into the malaria parasite cell invasion machinery and convincingly demonstrates that liver cell invasion is dramatically reduced by 95 % in the presence of the small molecule stabilizer compound 24.Fil: Nemetski, Sondra Maureen. New York University School of Medicine; Estados Unidos. New York-Presbyterian Hospital-Weill Cornell Medical College; Estados UnidosFil: Cardozo, Timothy J.. New York University School of Medicine; Estados UnidosFil: Bosch, Gundula. Johns Hopkins University Bloomberg School of Public Health; Estados Unidos. Johns Hopkins Malaria Research Institute ; Estados UnidosFil: Weltzer, Ryan. Johns Hopkins University Bloomberg School of Public Health; Estados Unidos. Johns Hopkins Malaria Research Institute ; Estados UnidosFil: O'Malley, Kevin. Johns Hopkins University Bloomberg School of Public Health; Estados Unidos. Johns Hopkins Malaria Research Institute ; Estados UnidosFil: Ejigiri, Ijeoma. New York University School of Medicine; Estados UnidosFil: Kumar, Kota Arun. New York University School of Medicine; Estados Unidos. University of Hyderabad; Estados UnidosFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; ArgentinaFil: Nussenzweig, Victor. New York University School of Medicine; Estados UnidosFil: Sinnis, Photini. Johns Hopkins University Bloomberg School of Public Health; Estados Unidos. New York University School of Medicine; Estados Unidos. Johns Hopkins Malaria Research Institute; Estados UnidosFil: Levitskaya, Jelena. Johns Hopkins University Bloomberg School of Public Health; Estados Unidos. Johns Hopkins Malaria Research Institute; Estados UnidosFil: Bosch, Jürgen. Johns Hopkins University Bloomberg School of Public Health; Estados Unidos. Johns Hopkins Malaria Research Institute; Estados Unido