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Item Structural and biophysical analysis of cytochrome P450 2C9*14 and *27 variants in complex with losartan.(Journal of Inorganic Biochemistry, 2024-09)The human cytochrome P450 (CYP) 1, 2 and 3 families of enzymes are responsible for the biotransformation of a majority of the currently available pharmaceutical drugs. The highly polymorphic CYP2C9 predominantly metabolizes many drugs including anticoagulant S-warfarin, anti-hypertensive losartan, anti-diabetic tolbutamide, analgesic ibuprofen, etc. There are >80 single nucleotide changes identified in CYP2C9, many of which significantly alter the clearance of important drugs. Here we report the structural and biophysical analysis of two polymorphic variants, CYP2C9*14 (Arg125His) and CYP2C9*27 (Arg150Leu) complexed with losartan. The X-ray crystal structures of the CYP2C9*14 and *27 illustrate the binding of two losartan molecules, one in the active site near heme and another on the periphery. Both losartan molecules are bound in an identical conformation to that observed in the previously solved CYP2C9 wild-type complex, however, the number of losartan differs from the wild-type structure, which showed binding of three molecules. Additionally, isothermal titration calorimetry experiments reveal a lower binding affinity of losartan with *14 and *27 variants when compared to the wild-type. Overall, the results provide new insights into the effects of these genetic polymorphisms and suggests a possible mechanism contributing to reduced metabolic activity in patients carrying these alleles.Item Pharmacy Intern Involvement in COVID-19 Immunization Practices in New York State.(Journal of Pharmacy Practice, 2024-06)Background: Pharmacists and pharmacy interns were instrumental in vaccination efforts during the COVID-19 pandemic. Objectives: To identify pharmacy intern involvement in COVID-19 immunization practices in New York State (NYS) and explore interns' perceptions of experiences. Methods: A 34-item survey was developed and administered at 5 pharmacy programs in NYS. Data collected included: perceptions of immunization readiness, participation in immunizations, description of experiences, and perceptions on the role of pharmacists. Respondents also reported on their preparedness to participate in the immunization process and the types of questions received from patients. Data were analyzed using descriptive statistics and thematic analysis. Questions regarding student experiences before and after participating in immunization efforts were analyzed using a two-sample t test. Results: A total of 460 interns participated in the survey with 398 (87%) reporting participation in COVID-19 immunizations. Of those, 231 (58%) participated at work, 146 (36.7) during experiential rotations, and 98 (24.6%) during volunteer experiences. Respondents participated in various components of vaccine delivery including administration (n = 246, 61.8%). Respondents administered an estimated 57,100 COVID-19 vaccines from December 2020 to April 2021 resulting in significantly higher mean scores for comfort level (5-point Likert scale) administering vaccines after participation (mean score 4.08 ± 1.31) compared to before (mean score 3.61 ± 1.42) (p < .0001). Themes which emerged regarding student perceptions of their experience are described. Conclusion: Pharmacy intern involvement in NYS COVID-19 immunization practices contributed to public health vaccination efforts. Additionally, interns improved comfort levels with immunization administration and recognized pharmacists' emerging roles within the U.S. healthcare system.Item HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology.(International Journal of Molecular Sciences, 4/25/2024)Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood-brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND.Item ACPHS Fourteenth Annual Research Symposium(2024-04-04)Item 2024-2025 ACPHS Scholarship of Discovery Award Recipients(2024-04-04)The College created the longstanding Scholarship of Discovery research grant program to invest in faculty who are conducting work that addresses important research questions, including scientific, clinical, historical, cultural, and literary pursuits.
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