This study aims to examine the cytotoxicity mechanisms of synthetic cathinone (bath salts) on rat primary cultured neurons and primary astroglial cells, and to assess their neurobehavioral effects on mice. We administered methylenedioxypyrovalerone (MDPV) to both rat primary cultured neurons and primary astroglial cells to assess cell injury. We also analyzed the effects of MDPV on these cell cultures using immunocytochemistry. We utilized western blotting to assess the breakdown of αII-spectrin and glial fibrillary acidic protein (GFAP) induced by MDPV. The western blotting experiment also included calpain and caspase inhibitors (SNJ1945 and Z-D-DCB, respectively) and pro-apoptotic and pro-necrotic agents (Staurosporine and calcium ionophore A23187, respectively). Lastly, we assessed MDPV’s effects on behavioral effects using rotarod, locomotor activity, elevated plus maze, Morris water maze, forced swimming, and open field tests. MDPV caused a dose-dependent release of LDH in both cerebrocortical neuron-astroglia mixed cultures and primary astroglial cultures. MDPV also caused neurite breakages and astroglial process retraction on immunocytochemistry. Lastly, MDPV induced αII-spectrin breakdown in western blotting experiments. Co-administration of calpain and caspase inhibitors reduced the degradation of αII-spectrin and GFAP. MDPV administration also increased anxiety-like behavior and locomotor activity in the mice. Synthetic cathinones, which share structural similarities with methamphetamine, also induce significant neurotoxic effects and neurobehavioral effects on rodent models. These neurotoxic effects are likely mediated by calpain and caspase-induced apoptosis and necrosis, while astroglial death is likely only due to calpain activation. Therefore, further research may focus on pharmacological interventions targeting these pathways to mitigate the cytotoxic impact of cathinones in humans.

Introduction: Clostridioides difficile is the primary cause of healthcare-associated infectious diarrhea in hospitalized patients. The most common laboratory testing methods for C. difficile infection (CDI) are toxin detection via enzyme immunoassay (EIA) and polymerase chain reaction (PCR), which detect a toxogenic strain. This study examines the impact of Rhode Island’s largest hospital system changing from PCR-only to two-step CDI testing. Methods: A retrospective cohort study of 2,173 adult inpatients was conducted. Patients were grouped into two cohorts: those tested for toxigenic C. difficile via PCR-only (June 2019–May 2021, n = 1,194) and those tested with the two-step algorithm (June 2021–May 2023, n = 979). Cluster analysis identified patient risk groups for hypothesis generation, and complications such as death, colectomy, intensive care unit ICU transfer, and 30-day readmission were compared across these groups. Results: In the moderate-risk group, there was a significant reduction in ICU transfers and readmission rates with the two-step testing by 5% and 7%, respectively. There were no other significant differences in complications between testing groups. Anti-CDI antibiotics were discontinued in 15% ( n = 106) of EIA-negative patients in the two-step testing group. Moderate-risk patients were less likely to have treatment discontinued than severe-risk patients (OR = 2.00, p = 0.016). Discussion: The two-step testing algorithm did not negatively affect patient outcomes and led to a modest decrease in anti-CDI treatment, supporting the safety of two-step CDI testing in hospitalized patients.