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Previous large-scale vaccination clinics have been successful before the coronavirus disease 2019 (COVID-19) pandemic; however, owing to the strict storage requirements and pharmaceutical preparation needed for the COVID-19 vaccines, careful thought and planning were necessary to successfully deploy these clinics immediately after vaccine availability. The focus of this manuscript is to describe the development and implementation of COVID-19 vaccination clinics in a large public university, using professionals from within and outside of its health sciences schools.The primary objective of this project was to (1) implement COVID-19 vaccination clinics for university faculty, staff, students, and community members. Additional objectives of the clinics were to (2) actively incorporate pharmacy, nursing, and medical students into the clinic workflow; (3) promote interprofessional collaboration among faculty and students; and (4) assess patient satisfaction.The School of Pharmacy faculty, in conjunction with the Office of Strategic Initiatives, planned and coordinated COVID-19 vaccination clinics from December 2020 to July 2021. Students and faculty from schools of pharmacy, nursing, and medicine were used. COVID-19 vaccinations were offered to university faculty, staff, and students and community members based on the Centers for Disease Control and Prevention priority groups. The clinic processes were designed such that they could be scaled from 100 to 2,000 participants per day.The School of Pharmacy led approach was adjustable depending on the number of patients, continuously monitored and adaptable. The importance of pharmacists as part of the interprofessional health care team was exemplified by faculty and students involved.All patients receiving COVID-19 vaccinations at the clinics were e-mailed anonymous surveys for assessment of the quality of the vaccination encounter after completion of their primary vaccine series.More than 15,000 COVID-19 vaccinations were provided through the clinics from December 2020 to July 2021. Professional staffing totaled 3352 hours for the 48 clinics. Thirty-eight percent of the vaccinated patients responded to the clinic satisfaction survey with predominately excellent ratings.COVID-19 vaccination clinics can be successfully planned and implemented in a scalable fashion in a large university setting using an interprofessional team approach.

Pharmacy students experience high levels of perceived stress. Data regarding the impact of curricular revision on students' stress level are lacking. The primary objective of this study was to compare perceived stress, academic self-concept, and coping strategies between pharmacy students prior to and following a curricular revision. Secondary objectives included determining university resources used by students to deal with stress.Students in the first, second, and third years of the pharmacy curriculum were asked to complete a survey, including the 14-item Perceived Stress Scale (PSS-14), Brief COPE, and Academic Self-Concept Scale (ASCS), and questions regarding use of university resources. Responses to the PSS-14, Brief COPE, and ASCS were compared to a student cohort prior to the curricular revision.Perceived stress was reduced to a small, statistically significant degree following a curricular revision. In both cohorts, increased stress was statistically significantly correlated with decreased academic self-concept. Students reported increased use of self-distraction, along with decreased use of active coping, substance abuse, and planning, as coping strategies when compared to the previous cohort. Approximately half of the student cohort reported no use of university resources. The most commonly used resources were financial aid and mental health services.Perceived stress decreased following the revision of a Doctor of Pharmacy curriculum. The most common coping strategies were positive and comparable with strategies reported by students in the former curriculum. The impact of curricular changes on student stress and the use of university resources in health professions students warrant further study.

Objective. To describe the development and assessment of an integrated virtual escape room in a cardiology course. Methods. A virtual escape room was developed to reinforce therapeutics, pharmacology, pharmacokinetics, medicinal chemistry, pharmacogenomics, and calculations related to cardiology in an integrated pharmacy course and was completed by two student cohorts. Groups of four to five students had 40 minutes to complete virtual escape room puzzles, and each puzzle had to be solved correctly prior to advancing. After completion of the activity, learners met with facilitators to debrief. Students completed pre- and postsurveys to assess knowledge changes and their perceptions of the experience. Results. One hundred twenty-six second-year Doctor of Pharmacy (PharmD) students completed the escape room, and 79% (n=55) and 93% (n=52) of students completed pre- and postsurveys for the 2020 and 2021 cohorts, respectively. Results showed a significant improvement in student knowledge on pre- to postsurvey knowledge questions (2020 presurvey mean [SD]=43.1 [22.6], postsurvey mean [SD]=74.1 [19.6]; 2021 presurvey mean [SD]=52.0 [15.8], postsurvey mean [SD]=67.1 [19.2]). Most students in both cohorts (88%) agreed that logistics of the escape rooms were amenable to learning and applying information, and 86% enjoyed working through puzzles. Conclusion. The virtual escape room was well received by students and served as an effective tool for reinforcing and integrating cardiology concepts. The virtual nature of the activity makes it practical and easily replicable to implement at other institutions, which can benefit from using the format, logistics, and materials described in this study to decrease faculty workload and costs associated with implementing this educational technique.

Supplementary Figures S1-S2 from Evaluation of Lapatinib and Topotecan Combination Therapy: Tissue Culture, Murine Xenograft, and Phase I Clinical Trial Data

Purpose: Topotecan resistance can result from drug efflux by P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) as well as survival signals initiated by epidermal growth factor receptor family members. The present studies were done to determine the effect of combining topotecan and the dual epidermal growth factor receptor/HER2 inhibitor lapatinib in tissue culture, a murine xenograft model, and a phase I clinical trial.Experimental Design: The effects of lapatinib on topotecan accumulation and cytotoxicity in vitro were examined in paired cell lines lacking or expressing Pgp or BCRP. Antiproliferative effects of the combination were assessed in mice bearing HER2+ BT474 breast cancer xenografts. Based on tolerability in this preclinical model, 37 patients with advanced-stage cancers received escalating doses of lapatinib and topotecan in a phase I trial.Results: Lapatinib increased topotecan accumulation in BCRP- or Pgp-expressing cells in vitro, and the combination showed enhanced efficacy in HER2+ BT474 xenografts. In the phase I study, nausea, vomiting, diarrhea, and fatigue were dose limiting. The maximum tolerated doses were 1,250 mg/d lapatinib by mouth for 21 or 28 days with 3.2 mg/m2 topotecan i.v. on days 1, 8, and 15 of 28-day cycles. Pharmacokinetic analyses showed that combined drug administration resulted in decreased topotecan clearance consistent with transporter-mediated interactions. Seventeen (46%) patients had disease stabilization.Conclusions: The lapatinib/topotecan combination is well tolerated and warrants further study.

d-Pinitol (3-O-methyl-d-chiro-inositol) is a cyclitol nearly ubiquitous in the Leguminosae and Pinaceae families. It plays an important role in plants as physiological cellular modulator and chemical defense against unfavorable environmental conditions, such as water deficit and high level of salinity. Plants rich in d-pinitol are being used in traditional medicine as empirical treatment for diabetes, inflammation, cancer or infections. This review summarizes the extensive literature published about d-pinitol biosynthesis, plant distribution, biological activities and pharmacological studies, including in vitro, in vivo, and clinical trials.

// Joseph R. McDermott 1 , Xiangrong Geng 1 , Lan Jiang 1 , Marina Galvez-Peralta 2 , Fei Chen 3 , Daniel W. Nebert 2 , Zijuan Liu 1 1 Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA 2 Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA 3 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA Correspondence to: Daniel W. Nebert, email: dan.nebert@uc.edu Zijuan Liu, email: liu2345@oakland.edu Keywords: selenite, zinc, micronutrient, ZIP8, membrane-bound transporter Received: December 26, 2015 Accepted: April 11, 2016 Published: May 6, 2016 ABSTRACT Selenite (HSeO 3 − ) is a monovalent anion of the essential trace element and micronutrient selenium (Se). In therapeutic concentrations, HSeO 3 − has been studied for treating certain cancers, serious inflammatory disorders, and septic shock. Little is known, however, about HSeO 3 − uptake into mammalian cells; until now, no mammalian HSeO 3 − uptake transporter has been identified. The ubiquitous mammalian ZIP8 divalent cation transporter (encoded by the SLC39A8 gene) is bicarbonate-dependent, moving endogenous substrates (Zn 2+ , Mn 2+ , Fe 2+ or Co 2+ ) and nonessential metals such as Cd 2+ into the cell. Herein we studied HSeO 3 − uptake in: human and mouse cell cultures, shRNA-knockdown experiments, Xenopus oocytes, wild-type mice and two transgenic mouse lines having genetically altered ZIP8 expression, and mouse erythrocytes ex vivo . In mammalian cell culture, excess Zn 2+ levels and/or ZIP8 over-expression can be associated with diminished viability in selenite-treated cells. Intraperitoneal HSeO 3 − causes the largest ZIP8-dependent increases in intracellular Se content in liver, followed by kidney, heart, lung and spleen. In every model system studied, HSeO 3 − uptake is tightly associated with ZIP8 protein levels and sufficient Zn 2+ and HCO 3 − concentrations, suggesting that the ZIP8-mediated electroneutral complex transported contains three ions: Zn 2+ /(HCO 3 − )(HSeO 3 − ). Transporters having three different ions in their transport complex are not without precedent. Although there might be other HSeO 3 − influx transporters as yet undiscovered, data herein suggest that mammalian ZIP8 plays a major role in HSeO 3 − uptake.

Slc39a8 encodes ZIP8, a divalent cation/bicarbonate symporter expressed in pluripotent mouse embryonic stem cells, and therefore ubiquitous in adult tissues; ZIP8 influxes Zn2+, Mn2+ and Fe2+. Slc39a8(neo/neo) knockdown mice exhibit 10–15% of wild-type ZIP8 mRNA and protein levels, and show pleiotropic phenotype of stunted growth, neonatal lethality, multi-organ dysmorphogenesis, and dysregulated hematopoiesis manifested as severe anemia. Herein we performed RNA-seq analysis of gestational day (GD)13.5 yolk sac and placenta, and GD16.5 liver, kidney, lung, heart and cerebellum, comparing Slc39a8(neo/neo) with Slc39a8(+/+) wild-type. Meta-data analysis of differentially-expressed genes revealed 29 unique genes from all tissues — having enriched GO categories associated with hematopoiesis and hypoxia and KEGG categories of complement, response to infection, and coagulation cascade — consistent with dysregulated hematopoietic stem cell fate. Based on transcription factor (TF) profiles in the JASPAR database, and searching for TF-binding sites enriched by Pscan, we identified numerous genes encoding zinc-finger and other TFs associated with hematopoietic stem cell functions. We conclude that, in this mouse model, deficient ZIP8-mediated divalent cation transport affects zinc-finger (e.g. GATA proteins) and other TFs interacting with GATA proteins (e.g. TAL1), predominantly in yolk sac. These data strongly support the phenotype of dysmorphogenesis and anemia seen in Slc39a8(neo/neo) mice in utero.

Perceptions and challenges connecting Pharmacogenomics taught in classrooms and translationing it to advance pharmacy practice rotations and healthcare settings and potential areas of development.

Objective. To develop an effective method in teaching pharmacogenomics as a part of a new course, Biopharmaceutics and Pharmacogenomics. Methods. Teaching effectiveness was measured by quizzes, retrospective pre- and post-surveys, team activities, and journal reflections. Four team activities were included in the course: genomic disease, patient case, genetic counselor and a debate about personalized medicine. Outcomes and course impact were evaluated at the end of the course. The evaluation methods included the assessment of knowledge, students' perceptions regarding the utility of team activities, the impact of the course on students' confidence to discuss pharmacogenomics with health care providers or patients, and long-term knowledge retention, measured in the following P2 semester. Results. Seventy-six students were enrolled in the course. Multiple assessments during the course demonstrated that students' knowledge of pharmacogenomics improved. The team activities had a positive impact on student learning, and the course improved their confidence level to discuss pharmacogenomics with another health care provider or a patient. While 86% of the students considered themselves "unconfident," "somewhat unconfident" or "neither confident nor unconfident" at the beginning of the course, 91% reported being "confident" or "somewhat confident" by the end of the course. This increase in confidence was statistically significant. Furthermore, students showed knowledge retention six months after taking the course. Conclusion. Implementation of a new course in pharmacogenomics was effective and well received by the students. It also prepared students for system-based therapeutics courses later in the curriculum.