XPO1 inhibition by selinexor induces potent cytotoxicity against high grade bladder malignancies.

Treatment options for high grade urothelial cancers are limited and have remained largely unchanged for several decades. Selinexor (KPT-330), a first in class small molecule that inhibits the nuclear export protein XPO1, has shown efficacy as a single agent treatment for numerous different malignancies, but its efficacy in limiting bladder malignancies has not been tested. In this study we assessed selinexor-dependent cytotoxicity in several bladder tumor cells and report that selinexor effectively reduced XPO1 expression and limited cell viability in a dose dependent manner. The decrease in cell viability was due to an induction of apoptosis and cell cycle arrest. These results were recapitulated in in vivo studies where selinexor decreased tumor growth. Tumors treated with selinexor expressed lower levels of XPO1, cyclin A, cyclin B, and CDK2 and increased levels of RB and CDK inhibitor p27, a result that is consistent with growth arrest. Cells expressing wildtype RB, a potent tumor suppressor that promotes growth arrest and apoptosis, were most susceptible to selinexor. Cell fractionation and immunofluorescence studies showed that selinexor treatment increased nuclear RB levels and mechanistic studies revealed that RB ablation curtailed the response to the drug. Conversely, limiting CDK4/6 dependent RB phosphorylation by palbociclib was additive with selinexor in reducing bladder tumor cell viability, confirming that RB activity has a role in the response to XPO1 inhibition. These results provide a rationale for XPO1 inhibition as a novel strategy for the treatment of bladder malignancies

Use of Concept Mapping to Identify Expectations of Pharmacy Students Selecting Elective Courses

The objective of this study was to demonstrate the use of concept mapping as a method for analyzing pharmacy students’ qualitative perceptions of their expectations of elective courses and to thus help guide delivery methods and course content. A survey containing demographic, Likert scale, and open-ended questions was administered to second-year pharmacy students prior to the start of elective courses and an innovative methodology, concept mapping, was used to identify major themes relating to student expectations. The association between preferred class delivery method (online versus in person) with student gender and English-as-a-second-language status (ESL) was also assessed. Note that this study was conducted prior to the COVID-19 pandemic. Ninety-eight out of 133 students (74%) completed the survey. Overall, 56% students stated that they preferred online delivery of courses (68% of these students were female, 36% were male). ESL status did not impact preference. The most common themes relating to student course expectations were the desire to learn about the elective course topic as well “real-world” utility. Our combined data indicate that delivery method is a key factor contributing to students’ choice of elective course and that concept mapping is an effective and efficient way to help identify student expectations of elective courses

Use of Concept Mapping to Identify Expectations of Pharmacy Students Selecting Elective Courses

The objective of this study was to demonstrate the use of concept mapping as a method for analyzing pharmacy students’ qualitative perceptions of their expectations of elective courses and to thus help guide delivery methods and course content. A survey containing demographic, Likert scale, and open-ended questions was administered to second-year pharmacy students prior to the start of elective courses and an innovative methodology, concept mapping, was used to identify major themes relating to student expectations. The association between preferred class delivery method (online versus in person) with student gender and English-as-a-second-language status (ESL) was also assessed. Note that this study was conducted prior to the COVID-19 pandemic. Ninety-eight out of 133 students (74%) completed the survey. Overall, 56% students stated that they preferred online delivery of courses (68% of these students were female, 36% were male). ESL status did not impact preference. The most common themes relating to student course expectations were the desire to learn about the elective course topic as well “real-world” utility. Our combined data indicate that delivery method is a key factor contributing to students’ choice of elective course and that concept mapping is an effective and efficient way to help identify student expectations of elective courses

Use of Team-Based Learning Pedagogy to Prepare for a Pharmacy School Accreditation Self-Study

Ensuring adequate engagement and preparation of all stakeholders in an accreditation self-study can be challenging for many reasons, including lack of motivation and inadequate understanding of expectations and procedures. The goal of this exploratory study was to determine whether using team-based learning (TBL) pedagogy to deliver an accreditation preparation workshop could effectively prepare and engage participants. A Likert-scale questionnaire was administered to workshop attendees (n = 52) to determine whether they found TBL-based training helpful and whether it promoted engagement. Twenty-four attendees completed the survey (46%). More than 80% of participants strongly agreed or agreed with 12 statements relating to perceptions of self and participant engagement within team activities and the usefulness of team activities. More than 65% of participants strongly agreed or agreed with statements relating to the helpfulness of the TBL approach in preparing for the self-study (five questions). Subgroup analysis showed no significant difference in responses based on whether on not participants had previously been involved in an accreditation self study. Our data indicate that a TBL approach can be an effective way to engage and prepare stakeholders for an accreditation self-study, and that TBL pedagogy has utility outside of the classroom setting

Impact of Completion of a Pre-Pharmacy Biochemistry Course and Competency Levels in Pre-Pharmacy Courses on Pharmacy Student Performance

Poor performance in foundational science courses, which are usually taken during the first or second year of pharmacy school, can have several negative consequences including increases in student drop-out rates and increases in the number of dismissals and remediating students. The primary goal of the current study was to determine whether completion of a pre-pharmacy biochemistry course and/or performance on a biochemistry competency test (administered at the beginning of the pharmacy program) are associated with pharmacy student performance in foundational science courses and overall academic performance. A secondary goal was to determine whether performance in pre-pharmacy courses and/or student demographics are associated with pharmacy student performance. Prospective univariate analyses (n = 75) determined that completion of a pre-pharmacy biochemistry course is not associated with pharmacy student performance. However, performance on a biochemistry competency test was associated with performance in Biochemistry and Cell&Molecular Biology (p = 0.002). Furthermore, post-hoc analyses determined that pre-pharmacy cumulative chemistry GPA correlates with performance in both the Biochemistry and Cell&Molecular Biology and Medicinal Chemistry foundational science courses (p = 0.002 and p = 0.04, respectively) and can predict first year GPA (p = 0.002). The combined data indicate that further assessment of the impact of pre-pharmacy competency in biochemistry and chemistry on pharmacy student success is warranted

Use of RNA-Seq and a Transgenic Mouse Model to Identify Genes Which May Contribute to Mutant p53-Driven Prostate Cancer Initiation

We previously demonstrated that the Trp53-R270H mutation can drive prostate cancer (CaP) initiation using the FVB.129S4 (Trp53tm3Tyj/wt); FVB.129S (Nkx3-1tm3(cre)Mmswt) genetically engineered mouse model (GEM). We now validate this finding in a different model (B6.129S4-Trp53tm3.1Tyj/J mice) and use RNA-sequencing (RNA-Seq) to identify genes which may contribute to Trp53 R270H-mediated prostate carcinogenesis. Wildtype (Trp53WT/WT), heterozygous (Trp53R270H/WT), and homozygous mice (Trp53R270H/R270H) were exposed to 5 Gy irradiation to activate and stabilize p53, and thereby enhance our ability to identify differences in transcriptional activity between the three groups of mice. Mouse prostates were harvested 6 h post-irradiation and processed for histological/immunohistochemistry (IHC) analysis or were snap-frozen for RNA extraction and transcriptome profiling. IHC analyses determined that presence of the Trp53-R270H mutation impacts apoptosis (lower caspase 3 activity) but not cell proliferation (Ki67). RNA-Seq analysis identified 1378 differentially expressed genes, including wildtype p53 target genes (E.g., Cdkn1a, Bax, Bcl2, Kras, Mdm2), p53 gain-of-function (GOF)-related genes (Mgmt, Id4), and CaP-related genes (Cav-1, Raf1, Kras). Further understanding the mechanisms which contribute to prostate carcinogenesis could allow for the development of improved preventive methods, diagnostics, and treatments for CaP

Effectiveness of an Advanced Naloxone Training, Simulation, and Assessment of Second-Year Pharmacy Students

Background: Opioid overdoses continue to be one of the most urgent public health priorities. In 2020, reported overdose deaths in the United States reached a high of over 93,000 cases. As the COVID-19 pandemic and opioid crisis continues to be addressed, life-saving agents must be more widely accessible to those with a high overdose risk. An essential step to increasing access is to train student pharmacists to dispense naloxone. Once licensed, the number of personnel authorized to dispense naloxone can increase. Objectives: To design a training program to educate second-year pharmacy (P2) students on furnishing naloxone under a state protocol. Methods: A multi-phased curriculum-based naloxone training program was delivered to P2 students and included lecture-based education, team-based learning (TBL) applications, case-based scenarios, and summative assessments to improve student knowledge and confidence in furnishing naloxone. Students were surveyed on their knowledge and confidence with naloxone prior to training, after the in-class training and TBL applications and after three assessments. Assessments included simulated patient counseling, case-based scenarios, and proper dispensing of naloxone in a community pharmacy simulation lab. Results: A total of 185 student pharmacists completed the naloxone training program and 68 completed all three surveys. Average scores for naloxone assessments were 83% for the APPS lab patient case, 90.5% for the prescription label typed for the naloxone product, and 88.5% for patient counseling. Statistically significant increases in knowledge-based quiz-like scores (42.1% after training vs. 7.2% after assessment) and in the proportion of students affirmatively answering survey questions after training and assessment was observed. Conclusion: Multi-phase curriculum-based naloxone training program improved pharmacy student knowledge and confidence in furnishing naloxone under a state BOP protocol