Fulfilling the Tripartite Mission During a Pandemic.

This commentary examines the challenges pharmacy faculty members have faced while working to fulfill their school's tripartite mission of teaching, research, and service during the coronavirus identified in 2019 (COVID-19) pandemic. It also outlines considerations that need to be made before moving forward regarding communication, collaboration, and culture. The pandemic has created opportunities for pharmacy educators to take instructional risks and attempt new didactic and experiential teaching methods and assessment strategies. Working remotely has not only altered pharmacy education, but also scholarship and service. Conducting a broad range of collaborations with accelerated timelines to address COVID-19 has in some instances forged new relationships both between and within universities and focused faculty members on grantsmanship and writing. Faculty governance and administrative leadership have been focused on solving challenges resulting from the COVID-19 pandemic in a collaborative, transparent approach guided by faculty bylaws. Programs have found ways to use these changes to their advantage while advancing the mission of the Academy, which can contribute to changing the culture of how we interact and care about each other with the hope that the positive changes made have an enduring and meaningful impact for years to come.

Breaking Down Barriers to Pharmacy Graduate Education: The Report of the 2017-2018 Research and Graduate Affairs Committee.

EXECUTIVE SUMMARY The 2017-2018 Research and Graduate Affairs Committee (RGAC) was given three charges aimed at helping academic pharmacy address barriers that must be overcome by both students and schools to attract, retain, and support the development of a diverse, well-rounded, and successful graduate student population. These charges were (1) identifying teaching methodologies, tools and opportunities that graduate programs can introduce into curriculum to overcome barriers to success of today's and tomorrow's learners; (2) developing a strategy for achieving member support of the 2016-2017 recommended graduate competencies by identifying gaps in and existing examples of courses or opportunities that achieve competency-based pharmacy graduate education; and (3) identifying potential strategies to address identified barriers to pursuing graduate education, especially among under-represented student populations. This report describes attitudes toward and opportunities related to competency-based education in graduation education in colleges and schools of pharmacy, identifies types of tools schools could use to enhance training towards the competency framework developed by the 2016-2017 RGAC, particularly with regards to the so-called power skills, and outlines a role for AACP in facilitating this training. This report also considers a number of barriers, both perceived and real, that potential students encounter when considering graduate training and suggests strategies to understand the impact of and mitigate these barriers. To strengthen competency-based graduate education, the RGAC puts forth two recommendations that AACP develop a toolkit supporting the training of power skills and that AACP should develop or curate programs or tools to support the use of individual development plans (IDPs). The RGAC also puts forth a suggestion to schools that IDPs be implemented for all students. In considering the barriers to pursuing graduate education, the Committee proposes one policy statement that AACP supports the training and development of an increasingly diverse population of researchers at pharmacy schools through active efforts to promote M.S. and Ph.D. education along with Pharm.D. education. Additionally, the Committee provides recommendations that AACP should expand its efforts in career tracking of graduate students to include collection and/or analysis of data that could inform the Academy's understanding of barriers to pursuing graduate education in pharmacy schools, the AACP Office of Institutional Research and Effectiveness should expand upon graduate program data described in the annual Profile of Pharmacy Students report, and finally that AACP should include graduate programs in efforts to increase diversity of students at pharmacy schools.

Competency, Programming, and Emerging Innovation in Graduate Education within Schools of Pharmacy: The Report of the 2016-2017 Research and Graduate Affairs Committee.

Graduate education in the pharmaceutical sciences is a cornerstone of research within pharmacy schools. Pharmaceutical scientists are critical contributors to addressing the challenges of new drug discovery, delivery, and optimal care in order to ensure improved therapeutic outcomes in populations of patients. The American Association of Colleges of Pharmacy (AACP) charged the 2016-2017 Research and Graduate Affairs Committee (RGAC) to define the competencies necessary for graduate education in the pharmaceutical sciences (Charge 1), recommend collaborative curricular development across schools of pharmacy (Charge 2), recommend AACP programing for graduate education (Charge 3), and provide guidance on emerging areas for innovation in graduate education (Charge 4). With respect to Charges 1 and 2, the RGAC committee developed six domains of core competencies for graduate education in the pharmaceutical sciences as well as recommendations for shared programming. For Charge 3, the committee made 3 specific programming recommendations that include AACP sponsored regional research symposia, a professional development forum at the AACP INterim Meeting, and the addition of a graduate research and education poster session at the AACP Annual Meeting. For Charge 4, the committee recommended that AACP develop a standing committee of graduate program deans and directors to provide guidance to member schools in support of graduate program representation at AACP meetings, develop skills for interprofessional teamwork and augment research through integration of Pharm.D., Ph.D., postdoctoral associates, resident, and fellow experiences. Two proposed policy statements by the committee are that AACP believes core competencies are essential components of graduate education and AACP supports the inclusion of research and graduate education focuses in its portfolio of meetings and programs.

Biomimicking Robust Hydrogel for the Mesenchymal Stem Cell Carrier.

PURPOSE: This study was aimed to develop a hydrogel-nanofiber as an advanced carrier for adipose derived human mesenchymal stem cells (AD-MSCs) and evaluate its potential for immunomodulatory therapies applicable to surface coating of drug eluting stent (DES) against coronary artery diseases (CAD). METHODS: A mixture of dispersing-nanofibers (dNFs) and poly (ethylene glycol)-diacrylate (PEGDA) were blended with sodium alginate to achieve robust mechanical strength. The effects of stem cell niche on cell viability and proliferation rates were evaluated using LDH assay and alamar blue assay, respectively. The amount of Nile-red microparticles (NR-MPs) remained in the hydrogel scaffolds was examined as an index for the physical strength of hydrogels. To evaluate the immunomodulatory activity of AD-MSCs as well as their influence by ROS, the level of L-Kynurenine was determined as tryptophan replacement compounds in parallel with IDO secreted from AD-MSCs using a colorimetric assay of L-amino acid. RESULTS: Both SA-cys-PEG and SA-cys-dNF-PEG upon being coated on stents using electrophoretic deposition technique displayed superior mechanical properties against the perfused flow. d-NFs had a significant impact on the stability of SA-cys-dNF-PEG, as evidenced by the substantial amount of NR-MPs remained in them. An enhanced subcellular level of ROS by spheroidal cluster yielded the high concentrations of L-Kynurenine (1.67 ± 0.6 µM without H2O2, 5.2 ± 1.14 µM with 50 µM of H2O2 and 8.8 ± 0.51 µM with 100 µM of H2O2), supporting the IDO-mediated tryptophan replacement process. CONCLUSION: The "mud-and-straw" hydrogels are robust in mechanical property and can serve as an ideal niche for AD-MSCs with immunomodulatory effects.

Center for the Advancement of Pharmacy Education 2013 educational outcomes.

An initiative of the Center for the Advancement of Pharmacy Education (formerly the Center for the Advancement of Pharmaceutical Education) (CAPE), the CAPE Educational Outcomes are intended to be the target toward which the evolving pharmacy curriculum should be aimed. Their development was guided by an advisory panel composed of educators and practitioners nominated for participation by practitioner organizations. CAPE 2013 represents the fourth iteration of the Educational Outcomes, preceded by CAPE 1992, CAPE 1998 and CAPE 2004 respectively. The CAPE 2013 Educational Outcomes were released at the AACP July 2013 Annual meeting and have been revised to include 4 broad domains, 15 subdomains, and example learning objectives.

Sublethal total body irradiation leads to early cerebellar damage and oxidative stress.

The present study aimed at identifying early damage index in the cerebellum following total body irradiation (TBI). Adult male CD2F1 mice (n=18) with or without TBI challenge (8.5 Gy irradiation) were assessed for histology and expression of selected immunohistochemical markers including malondiadehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), protein 53 (p53), vascular endothelial growth factor receptor 2 (VEGF-R2), CD45, calbindin D-28k (CB- 28) and vesicular glutamate transport-2 (VGLUT2) in cerebellar folia II to IV. Compared to sham-controls, TBI significantly increased vacuolization of the molecular layer. At high magnification, deformed fiber-like structures were found along with the empty matrix space. Necrotic Purkinje cells were identified on 3.5 days after TBI, but not on 1 day. Purkinje cell count was reduced significantly 3.5 days after TBI. Compared with sham control, overall intensities of MDA and 8-OHdG immunoreactivities were increased dramatically on 1 and 3.5 days after TBI. Expression of VEGF-R2 was identified to be co-localized with 8-OHdG after TBI. This validates microvessel endothelial damage. The p53 immunoreactivities mainly deposited in the granular layer and microvessels after TBI and co-localization of the p53 with the CD45, both which were found within the microvessels. After TBI, CB28 expression decreased whereas the VGLUT2 expression increased significantly; Purkinje cells exhibited a reduced body size and deformity of dendritic arbor, delineated by CB28 immunoreactivity. Substantial damage to the cerebellum can be detectable as early as 1- 3.5 days in adult animals following sublethal TBI. Oxidative stress, inflammatory response and calcium neurotoxicity-associated mechanisms are involved in radiation-induced neuronal damage.

Cervical cancer isolate PT3, super-permissive for adeno-associated virus replication, over-expresses DNA polymerase delta, PCNA, RFC and RPA.

BACKGROUND: Adeno-associated virus (AAV) type 2 is an important virus due to its use as a safe and effective human gene therapy vector and its negative association with certain malignancies. AAV, a dependo-parvovirus, autonomously replicates in stratified squamous epithelium. Such tissue occurs in the nasopharynx and anogenitals, from which AAV has been clinically isolated. Related autonomous parvoviruses also demonstrate cell tropism and preferentially replicate in oncogenically transformed cells. Combining these two attributes of parvovirus tropism, squamous and malignant, we assayed if AAV might replicate in squamous cervical carcinoma cell isolates. RESULTS: Three primary isolates (PT1-3) and two established cervical cancer cell lines were compared to normal keratinocytes (NK) for their ability to replicate AAV. One isolate, PT3, allowed for high levels of AAV DNA replication and virion production compared to others. In research by others, four cellular components are known required for in vitro AAV DNA replication: replication protein A (RPA), replication factor C (RFC), proliferating cell nuclear antigen (PCNA), and DNA polymerase delta (POLD1). Thus, we examined PT3 cells for expression of these components by DNA microarray and real-time quantitative PCR. All four components were over-expressed in PT3 over two representative low-permissive cell isolates (NK and PT1). However, this super-permissiveness did not result in PT3 cell death by AAV infection. CONCLUSION: These data, for the first time, provide evidence that these four cellular components are likely important for AAV in vivo DNA replication as well as in vitro. These data also suggest that PT3 will be a useful reagent for investigating the AAV-permissive transcriptome and AAV anti-cancer effect.

Identifying perceptions of professionalism in pharmacy using a four-frame leadership model.

OBJECTIVES: To determine whether professionalism in pharmacy education is addressed from Bolman and Deal's four-frame leadership model. METHODS: Students (N=624), faculty (N=57), preceptors (N=56), and academic administrators (N=8) at 6 colleges and schools of pharmacy were surveyed to assess professionalism. Using grounded theory methodology and a constant comparative process, common themes were identified for each question in each group. Themes were assigned to the four-frame model and the data were compared. RESULTS: Mechanisms of addressing professionalism consistent with all 4 frames of the Bolman and Deal's model were identified. Faculty assessment of student professionalism was significantly lower (P<0.05) than the student group, preceptors, and administrators. CONCLUSIONS: Mechanisms of addressing professionalism in pharmacy education span all four frames of Bolman and Deal's leadership model. The values students bring into a pharmacy program may play an important role in the process of professional socialization. Faculty members have a tremendous opportunity to enhance student professionalism with their daily verbal and nonverbal interactions with students.

Acute dilatory and negative inotropic effects of homocysteine are inhibited by an adenosine blocker.

1. Previous studies have shown that homocysteine elicits acute negative inotropic and coronary vasodilatory effects in rat hearts. In addition, this earlier work suggested that the inotropic action is mediated via an endothelium-derived agent that is neither nitric oxide (NO) nor a cyclooxygenase product, while the coronary actions were found to be antagonized by the NOS inhibitor l-NNA. Current experiments, which utilized coronary-perfused rat hearts, were designed to determine if muscarinic or adenosine receptors are involved in these acute actions of homocysteine. 2. Left ventricular developed pressure was used as a measure of systolic function in electrically paced, Langendorff-perfused heart with coronary pressure being used to monitor coronary vascular tone. Acute effects of homocysteine (10-300 micromol/L) were examined in the presence and absence of 1 yen 10(-6) mol atropine or 7 yen 10(-5) mol 8-(p-sulfophenyl) theophylline (SPT), a non-selective adenosine receptor antagonist. 3. Atropine had no effect on either the inotropic or vascular actions of homocysteine. In contrast, SPT partially antagonized both actions of the amino acid with the antagonism of the vasodilation being much greater than its inhibition of the negative inotropic effect. Experiments with adenosine demonstrated that the selected dose of SPT elicited marked rightward shifts in the dose-response curves for both the inotropic and vascular actions. 4. Current results suggest that adenosine plays a role in both the negative inotropic and vasodilatory actions of homocysteine. However, the relatively minor antagonistic action of SPT on the inotropic effect of homocysteine suggests that additional endothelium-derived mediators underlie its effects on contractility.

Effect of long-term hyperhomocysteinemia on myocardial structure and function in hypertensive rats.

BACKGROUND: Postulated mechanisms of hyperhomocysteinemia (Hhe) overlap with proposed mechanisms of adverse cardiac remodeling such as altered collagen metabolism and oxidant stress. Hence we examined the hypothesis that Hhe would promote myocardial fibrosis and systolic dysfunction. METHODS: Three-month-old spontaneously hypertensive rats (SHRs) were divided into three groups: (1) control, given amino-acid defined diet for 20 weeks; (2) Hhe group, given Hhe-inducing diet for 20 weeks; and (3) combined diet group, which were given Hhe-inducing diet for 10 weeks (which leads to myocardial fibrosis and diastolic dysfunction as shown in our prior studies) and subsequently returned to amino acid-defined diet for 10 more weeks. At the end of the treatment period, plasma homocysteine (Hcy) levels and blood pressure were measured, and hearts were isolated for histomorphometric and biochemical assessment of cardiac remodeling and myocardial oxidative stress, and for in vitro cardiac function studies. RESULTS: The Hhe animals demonstrated a significant increase in the ratio of collagenous to noncollagenous protein due to reactive interstitial fibrosis, and increased myocardial oxidant stress, compared to the control group. Systolic function was significantly depressed in the Hhe animals compared to the control group. These changes were partially prevented by return to control diet at 10 weeks. CONCLUSIONS: Our results demonstrate that clinically relevant levels of Hhe accelerate progression of hypertensive heart disease to systolic dysfunction and that increased myocardial oxidant stress may play a role in this process. Considering the high prevalence of hypertension and Hhe in the general population, our findings may have great clinical significance.

Cardiovascular effects of hyperhomocysteinemia in conscious unrestrained rats.

BACKGROUND: Experiments were designed to determine whether hyperhomocysteinemia (Hhe) affects cardiovascular function when monitored in conscious unrestrained animals. METHODS: Adult, male Sprague-Dawley rats were fed a homocystine-supplemented diet for 6 months. Blood pressure (BP), heart rate, and pulse pressure were monitored continuously, 24 h a day, using biotelemetry techniques. RESULTS: The resulting intermediate level of Hhe was not associated with significant changes in heart rate, diastolic BP, systolic BP, or the circadian variation in heart rate. In spite of the lack of significant changes in systolic and diastolic BP, there was a slight but statistically significant increase in pulse pressure after 4 months of treatment that returned toward control levels after 6 months. CONCLUSIONS: Current results indicate that Hhe alone does not have significant effects on BP. Furthermore, they suggest that the previously reported Hhe-induced adverse cardiac remodeling and diastolic dysfunction in this animal model are not the result of pressure overload.

Gender differences in blood pressure and heart rate in spontaneously hypertensive and Wistar-Kyoto rats.

1. In general, premenopausal women are known to have lower blood pressure than men and animal models have shown a similar sexual dimorphism. However, many studies in animals have been performed using anaesthetized or restrained models. Current experiments were conducted to investigate the relationships among resting heart rate, blood pressure and gender in conscious, unrestrained normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Biotelemetry transmitters were implanted in 6-month-old animals. Values for heart rate, diastolic blood pressure, systolic blood pressure and pulse pressure were recorded continuously at 10 min intervals after all animals recovered completely from surgery. 3. Normal circadian rhythms in heart rate were found in all rats, with no significant differences among the four groups; the circadian variation in blood pressure was evident in all groups, although much smaller. Heart rate was found to be higher in WKY female rats than in the other three groups. Male WKY rats, male SHR and female SHR had similar heart rates. Male SHR had significantly higher systolic and diastolic blood pressures than female SHR. Male and female WKY rats had similar diastolic blood pressure, but males had slightly higher systolic pressure than females. No significant difference in pulse pressure was found in WKY male and female rats. Male SHR showed significantly higher pulse pressure than female SHR at most times during the day. 4. In conclusion, these results indicate that hypertension is exacerbated in male SHR compared with females under conscious resting conditions and demonstrate that the higher heart rate observed in WKY female rats is not present in the SHR model.

Hyperhomocysteinemia leads to pathological ventricular hypertrophy in normotensive rats.

A recent report indicated that hyperhomocysteinemia (Hhe), in addition to its atherothrombotic effects, exacerbates the adverse cardiac remodeling seen in response to hypertension, a powerful stimulus for pathological ventricular hypertrophy. The present study was undertaken to determine whether Hhe has a direct effect on ventricular remodeling and function in the absence of other hypertrophic stimuli. Male Wistar-Kyoto rats were fed either an amino acid-defined control diet or an intermediate Hhe-inducing diet. After 10 wk of dietary treatment, rats were subjected to echocardiographic assessment of left ventricular (LV) dimensions and systolic function. Subsequently, blood was collected for plasma homocysteine measurements, and the rats were killed for histomorphometric and biochemical assessment of cardiac remodeling and for in vitro cardiac function studies. Significant LV hypertrophy was detected by echocardiographic measurements, and in vitro results showed hypertrophy with significantly increased myocyte size in the LV and right ventricle (RV). LV and RV remodeling was characterized by a disproportionate increase in perivascular and interstitial collagen, coronary arteriolar wall thickening, and myocardial mast cell infiltration. In vitro study of LV function demonstrated abnormal diastolic function secondary to decreased compliance because the rate of relaxation did not differ between groups. LV systolic function did not vary between groups in vitro. In summary, in the absence of other hypertrophic stimuli short-term intermediate Hhe caused pathological hypertrophy and remodeling of both ventricles with diastolic dysfunction of the LV. These results demonstrate that Hhe has direct adverse effects on cardiac structure and function, which may represent a novel direct link between Hhe and cardiovascular morbidity and mortality, independent of other risk factors.

Interaction of xenobiotics with myocardial signal transduction pathways.

Although the understanding of how toxicants alter cardiac ion-channel function has matured rapidly over the past 20-30 yr, little is known about how xenobiotics may alter the signaling pathways of cardiac myocyte growth and death. Signaling molecules and pathways responsible for the growth of cardiac myocytes include the mitogen-activated protein kinases (MAPKs), janus kinase-signal transducer and activator of transcription (JAK-STATs), nuclear receptor signaling, calcineurin, and the mobilization of free calcium. Signaling molecules and pathways responsible for programmed cardiac myocyte death include the death receptors, mitochondrial proteins, p53 tumor suppressor protein, ceramide signaling, and caspases. Overlap or "crosstalk" between the various growth and death pathways in the myocardium is evident, and these pathways likely exist in a delicate balance where, for example, slight reductions in growth signaling may favor pathways leading to cardiac myocyte apoptosis. Several classical cardiotoxicants are now known to alter signaling pathways in cardiac myocytes; however, the significance of these effects is not entirely clear. Furthermore, xenobiotics that alter the interstitium or extracellular matrix, or both, may significantly alter signaling pathways in cardiac myocytes. The goal of this review is to summarize current findings regarding the interaction of xenobiotics with myocardial signal transduction pathways in the hope of stimulating new insights and highlighting important areas for future research.

Linoleic acid metabolites act to increase contractility in isolated rat heart.

Previous in vivo studies in dogs suggest that the 9,10-monoepoxide of linoleic acid (9,10-cis-epoxyoctadecenoic acid [9,10-EOA]) has toxic cardiovascular effects that result in death at higher doses. More recent work with rabbit renal proximal tubule cells suggests that the 12,13-metabolites of linoleic acid are more toxic than the 9,10-isomers. Thus, in the current study, we tested the hypothesis that 12,13-EOA and 12,13-dihydroxyoctadecadienoic acid (12,13-DHOA) have direct adverse effects on the heart. Langendorff-perfused rat hearts were exposed to 30 microM linoleic acid, 30 microM 12,13-EOA, or 30 microM 12,13-DHOA for 60 min followed by a 30-min recovery period. As indicated by peak left intraventricular pressure and/or +dP/dt(max), all three of the agents elicited moderate increases in contractile function that peaked within 10 20 min. The effects of linoleic acid and 12,13-EOA returned to control values during the remainder of the 60-min exposure, whereas the positive inotropic response to 12,13-DHOA was maintained until washout. Sustained arrhythmias and negative inotropic actions were not observed with any of the three compounds. Subsequently, the monoepoxides were infused into conscious rats (35 mg/kg/h) while blood pressure, heart rate, and EKG were monitored for 24 h using biotelemetry techniques. The only effect observed was a slight decline in blood pressure. Thus, current data suggest that linoleic acid and its oxidative metabolites do not have direct cardiotoxic effects during acute exposure.