Correction to: Imaging features of immune-mediated genitourinary disease.

The authors regret that they neglected to cite their conference report on the technical part of a 'preliminary study' presented at, and published in, the Biomedical Sciences and Engineering Conference (BSEC), 2010, May 25-26 (Fully automated segmentation and characterization of the dendritic trees of retinal horizontal neurons -DOI: 10.1109/BSEC.2010.5510843 ), as it related to the larger dataset presented as validation of the method in the Neurochemical Research article (Automated Tracing of Horizontal Neuron Processes During Retinal Development- Neurochem Res. 2011 Apr;36(4):583-93). This resulted in the lack of transparency on the re-use and duplication of introductory text, which should have been cited. No figures or tables were reproduced, but rather larger confirmatory data and different set of results were reported. Appropriate authors were cited in both papers.

Retinoblastoma (Rb) regulates laminar dendritic arbor reorganization in retinal horizontal neurons.

Neuronal differentiation with respect to the acquisition of synaptic competence needs to be regulated precisely during neurogenesis to ensure proper formation of circuits at the right place and time in development. This regulation is particularly important for synaptic triads among photoreceptors, horizontal cells (HCs), and bipolar cells in the retina, because HCs are among the first cell types produced during development, and bipolar cells are among the last. HCs undergo a dramatic transition from vertically oriented neurites that form columnar arbors to overlapping laminar dendritic arbors with differentiation. However, how this process is regulated and coordinated with differentiation of photoreceptors and bipolar cells remains unknown. Previous studies have suggested that the retinoblastoma (Rb) tumor suppressor gene may play a role in horizontal cell differentiation and synaptogenesis. By combining genetic mosaic analysis of individual synaptic triads with neuroanatomic analyses and multiphoton live imaging of developing HCs, we found that Rb plays a cell-autonomous role in the reorganization of horizontal cell neurites as they differentiate. Aberrant vertical processes in Rb-deficient HCs form ectopic synapses with rods in the outer nuclear layer but lack bipolar dendrites. Although previous reports indicate that photoreceptor abnormalities can trigger formation of ectopic synapses, our studies now demonstrate that defects in a postsynaptic partner contribute to the formation of ectopic photoreceptor synapses in the mammalian retina.

Predicting the Success of International Pharmacists in a Distance-Based US Doctor of Pharmacy (PharmD) Program: Results from a 5-Year Cohort.

Background: To establish the predictors of success in an international-trained PharmD (ITPD) program between admission criteria and academic performance. Methods: The primary outcome of this study was the correlation of admission criteria with didactic and experiential grade point averages (GPA) for the first 5 years. Candidates meeting the minimum criteria completed a competency exam or the US-Foreign Pharmacy Graduate Equivalency Exam (US-FPGEE). Tests of English language proficiency (TOEFL(R) and ACTFL's Oral Proficiency Interview) plus interview with faculty, students, and alumni were also required. Scores were correlated with both didactic and experiential GPAs. Results: The 23 students admitted to the ITPD program had a cumulative GPA of 3.72. There was a significant correlation between total admissions score and the median pharmacy and healthcare course category GPA (ρ 0.53), but not other categories. The composite TOEFL did not predict any performance but TOEFL writing and speaking did correlate with advanced pharmacy practice experience (APPE) performance. The OPI scores were associated with higher GPAs overall, in advanced integrated clinical sciences, and APPEs. The admission interview scores consistently and significantly correlated with preceptor-rated APPE GPA, practitioner skills, and professionalism (ρ > 0.5; p < 0.05). Performance in early courses significantly predicted the performance in advanced courses and experiential performance (ρ 0.48−0.61). Conclusion: The correlations between early and late course performance demonstrated the cohesiveness of this program. Further study is needed between the predictors of success using non-cognitive admission criteria.

Automated tracing of horizontal neuron processes during retinal development.

In the developing mammalian retina, horizontal neurons undergo a dramatic reorganization of their processes shortly after they migrate to their appropriate laminar position. This is an important process because it is now understood that the apical processes are important for establishing the regular mosaic of horizontal cells in the retina and proper reorganization during lamination is required for synaptogenesis with photoreceptors and bipolar neurons. However, this process is difficult to study because the analysis of horizontal neuron anatomy is labor intensive and time-consuming. In this paper, we present a computational method for automatically tracing the three-dimensional (3-D) dendritic structure of horizontal retinal neurons in two-photon laser scanning microscope (TPLSM) imagery. Our method is based on 3-D skeletonization and is thus able to preserve the complex structure of the dendritic arbor of these cells. We demonstrate the effectiveness of our approach by comparing our tracing results against two sets of semi-automated traces over a set of 10 horizontal neurons ranging in age from P1 to P5. We observe an average agreement level of 81% between our automated trace and the manual traces. This automated method will serve as an important starting point for further refinement and optimization.

Educational Methods and Technological Innovations for Introductory Experiential Learning Given the Contact-Related Limitations Imposed by the SARS-CoV2/COVID-19 Pandemic.

BACKGROUND: Acute respiratory syndrome related coronavirus disease (COVID-19) has led to substantial changes in pharmacy curricula, including the ability to provide in-person introductory experiential practice experiences (IPPEs) to University of Colorado's International-Trained PharmD (ITPD) students. METHODS: The IPPE course for ITPD students was redesigned to offer remote educational activities in the health system setting and simulated practice and communication activities in the community setting. Students were evaluated via surveys regarding the perceived value of these changes, and changes in knowledge, skills and abilities before and after activities. RESULTS: A total of 6 students were enrolled in the revised IPPE course. Students agreed or strongly agreed that the overall distance-based IPPE experience, the remote health system activities, and the community activities were valuable. Students also strongly agreed that course design successfully met course outcomes and was relevant to pharmacy practice. In terms of knowledge, skills and abilities, numeric improvements were observed in remote health system activities and community-based simulated patient interactions, but results were not statistically significant. A high baseline level of knowledge led to minimal improvements in perceptions of improvement in community pharmacy skills regarding pharmacy simulation software. CONCLUSION: Implementation of distance-based IPPE activities may be an alternate educational modality.

Interprofessional Master of Science in Palliative Care: On Becoming a Palliative Care Community Specialist.

Background: Palliative care (PC) is a limited resource in health care systems. Many providers develop a PC interest later in their careers when it is difficult to relocate and compete for a limited number of training positions. In communities without an academic tertiary medical center, interprofessional PC community specialists are poised to deliver high-quality accessible PC to patients/families with needs beyond what can be addressed by primary care providers. Objective: An interprofessional 36-credit Master of Science in Palliative Care (MSPC) provides evidence-based education to nurses, pharmacists, physicians, physician assistants, social workers, spiritual care providers, psychologists, counselors, and other allied health professionals. Design: The predominantly online curriculum, designed and taught by an interprofessional faculty, focuses on interdisciplinary teamwork, communication skills, and practical application of biomedical and psycho-sociocultural-spiritual-ethics content. The pedagogy is narrative based, emulating in-person clinical experiences, with patient cases progressing throughout the curriculum. We have enrolled four student cohorts. Measurements: Student self-assessments pre-mid-post program. Results: Students highly rate curriculum with demonstrated application of knowledge in case integration assignments, simulations with standardized patients, and Capstone Projects. Students' self-assessed skills on a 39-item scale increased on average to the highest level of 5 (able to perform independently and teach others). Conclusions: The inaugural student cohort reports high levels of engagement and satisfaction, including mastery and synthesis of didactic and experiential content through case integration projects. Students who worked in PC/hospice settings have advanced in their professions; others have transitioned to PC work. The MSPC has capacity to meet projected PC workforce gaps.

Five years of lesson modification to implement non-traditional learning sessions in a traditional-delivery curriculum: A retrospective assessment using applied implementation variables.

Non-traditional learning (NTL), including aspects of self-directed learning (SDL), may address self-awareness development needs. Many factors can impact successful implementation of NTL. OBJECTIVES: To share our multi-year experience with modifications that aim to improve NTL sessions in a traditional curriculum. To improve understanding of applied implementation variables (some of which were based on successful SDL implementation components) that impact NTL. METHODS: We delivered a single lesson in a traditional-delivery curriculum once annually for five years, varying delivery annually in response to student learning and reaction-to-learning results. At year 5, we compared student learning and reaction-to-learning to applied implementation factors using logistic regression. RESULTS: Higher instructor involvement and overall NTL levels predicted correct exam responses (p=0.0007 and p<0.0001, respectively). Exam responses were statistically equivalent between the most traditional and highest overall NTL deliveries. Students rated instructor presentation skills and teaching methods higher when greater instructor involvement (p<0.0001, both) and lower overall NTL levels (P<0.0001, both) were used. Students perceived that teaching methods were most effective when lower student involvement and higher technology levels (p<0.0001, both) were used. CONCLUSION: When implementing NTL sessions as a single lesson in a traditional-delivery curriculum, instructor involvement appears essential, while the impact of student involvement and educational technology levels varies.

Current Practices in Hosting Non-US Pharmacy Students at US Pharmacy Schools in Experiential Clerkships.

Objective: To provide specific considerations for hosting non-U.S. pharmacy students at U.S.-based colleges/schools of pharmacy (C/SOP) for experiential clerkships and training. Findings: A literature review (2000-2016) in PubMed, Google Scholar and IPA databases was conducted using specific keywords. Recommendations and future directions for development of experiential rotations for non-U.S. students in U.S. experiential rotations are presented for both the home and host country. Summary articles and best practices across the disciplines, as well as expert opinion, were found across U.S. models for hosting non-U.S. students in advanced practice rotations in the medical disciplines. Consistent themes regarding legal agreements, acculturation, standardized calendars and social and safety considerations were considered for inclusion in the final document. Conclusion: Development of a successful experiential rotation/training for non-U.S. students requires consideration for well-developed objectives, qualified preceptors, multitude of legal and cultural considerations and recommendations for longevity and sustainability.

Micro-imaging of amyloid in mice.

Scintigraphic imaging of radioiodinated serum amyloid P-component is a proven method for the clinical detection of peripheral amyloid deposits (Hawkins et al., 1990). However, the inability to perform comparably high-resolution studies in experimental animal models of amyloid disease has impacted not only basic studies into the pathogenesis of amyloidosis but also in the preclinical in vivo evaluation of potential anti-amyloid therapeutic agents. We have developed microimaging technologies, implemented novel computational methods, and established protocols to generate high-resolution images of amyloid deposits in mice. (125)I-labeled serum amyloid P component (SAP) and an amyloid-fibril reactive murine monoclonal antibody (designated 11-1F4) have been used successfully to acquire high-resolution single photon emission computed tomographic (SPECT) images that, when fused with x-ray computed tomographic (CT) data, have provided precise anatomical localization of secondary (AA) and primary (AL) amyloid deposits in mouse models of these diseases. This chapter will provide detailed protocols for the radioiodination and purification of amyloidophilic proteins and the generation of mouse models of AA and AL amyloidosis. A brief description of the available hardware and the parameters used to acquire high-resolution microSPECT and CT images is presented, and the tools used to perform image reconstruction and visualization that permit the analysis and presentation of image data are discussed. Finally, we provide established methods for measuring organ- and tissue-specific activities with which to corroborate the microSPECT and CT images.

Current Practices in Global/International Advanced Pharmacy Practice Experiences: Preceptor and Student Considerations.

The objective of this article is to describe the key areas of consideration for global/international advanced pharmacy practice experience (G/I APPE) preceptors, students and learning objectives. At the 2013 Annual Meeting of the American Association of Colleges of Pharmacy (AACP), the GPE SIG prepared and presented an initial report on the G/IAPPE initiatives. Round table discussions were conducted at the 2014 AACP Annual Meeting to document GPE SIG member input on key areas in the report. Literature search of PubMed, Google Scholar and EMBASE with keywords was conducted to expand this report. In this paper, considerations related to preceptors and students and learning outcomes are described. Preceptors for G/I APPEs may vary based on the learning outcomes of the experience. Student learning outcomes for G/I APPEs may vary based on the type of experiential site. Recommendations and future directions for development of G/IAPPEs are presented. Development of a successful G/I APPE requires significant planning and consideration of appropriate qualifications for preceptors and students.

Quantitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosis.

The mouse model of experimentally induced systemic AA amyloidosis is long established, well validated, and closely analogous to the human form of this disease. However, the induction of amyloid by experimental inflammation is unpredictable, inconsistent, and difficult to modulate. We have previously shown that murine AA amyloid deposits can be imaged using iodine-123 labeled SAP scintigraphy and report here substantial refinements in both the imaging technology and the mouse model itself. In this regard, we have generated a novel prototype of AA amyloid in which mice expressing the human interleukin 6 gene, when given amyloid enhancing factor, develop extensive and progressive systemic AA deposition without an inflammatory stimulus, i.e., a transgenic rapidly inducible amyloid disease (TRIAD) mouse. Additionally, we have constructed high-resolution micro single photon emission computed tomography (SPECT)/computed tomography (CT) instrumentation that provides images revealing the precise anatomic location of amyloid deposits labeled by radioiodinated serum amyloid P component (SAP). Based on reconstructed microSPECT/CT images, as well as autoradiographic, isotope biodistribution, and quantitative histochemical analyses, the (125)I-labeled SAP tracer bound specifically to hepatic and splenic amyloid in the TRIAD animals. The ability to discern radiographically the extent of amyloid burden in the TRIAD model provides a unique opportunity to evaluate the therapeutic efficacy of pharmacologic compounds designed to inhibit fibril formation or effect amyloid resolution.

Quantitative comparison of mitotic spindles by confocal image analysis.

The mitotic spindle is a subcellular protein structure that facilitates chromosome segregation and is crucial to cell division. We describe an image processing approach to quantitatively characterize and compare mitotic spindles that have been imaged three dimensionally using confocal microscopy with fixed-cell preparations. The proposed approach is based on a set of features that are computed from each image stack representing a spindle. We compare several spindle datasets of varying biological (genotype) and/or environmental (drug treatment) conditions. The goal of this effort is to aid biologists in detecting differences between spindles that may not be apparent under subjective visual inspection, and furthermore, to eventually automate such analysis in high-throughput scenarios (thousands of images) where manual inspection would be unreasonable. Experimental results on positive- and negative-control data indicate that the proposed approach is indeed effective. Differences are detected when it is known they do exist (positive control) and no differences are detected when there are none (negative control). In two other experimental comparisons, results indicate structural spindle differences that biologists had not observed previously.

Automated 3-D tracking of centrosomes in sequences of confocal image stacks.

In order to facilitate the study of neuron migration, we propose a method for 3-D detection and tracking of centrosomes in time-lapse confocal image stacks of live neuron cells. We combine Laplacian-based blob detection, adaptive thresholding, and the extraction of scale and roundness features to find centrosome-like objects in each frame. We link these detections using the joint probabilistic data association filter (JPDAF) tracking algorithm with a Newtonian state-space model tailored to the motion characteristics of centrosomes in live neurons. We apply our algorithm to image sequences containing multiple cells, some of which had been treated with motion-inhibiting drugs. We provide qualitative results and quantitative comparisons to manual segmentation and tracking results showing that our average motion estimates agree to within 13% of those computed manually by neurobiologists.

Myosin II motors and F-actin dynamics drive the coordinated movement of the centrosome and soma during CNS glial-guided neuronal migration.

Lamination of cortical regions of the vertebrate brain depends on glial-guided neuronal migration. The conserved polarity protein Par6alpha localizes to the centrosome and coordinates forward movement of the centrosome and soma in migrating neurons. The cytoskeletal components that produce this unique form of cell polarity and their relationship to polarity signaling cascades are unknown. We show that F-actin and Myosin II motors are enriched in the neuronal leading process and that Myosin II activity is necessary for leading process actin dynamics. Inhibition of Myosin II decreased the speed of centrosome and somal movement, whereas Myosin II activation increased coordinated movement. Ectopic expression or silencing of Par6alpha inhibited Myosin II motors by decreasing Myosin light-chain phosphorylation. These findings suggest leading-process Myosin II may function to "pull" the centrosome and soma forward during glial-guided migration by a mechanism involving the conserved polarity protein Par6alpha.