Quantification of Morphological Modulation, F-Actin Remodeling, and PECAM-1 (CD-31) Redistribution in Endothelial Cells in Response to Fluid-Induced Shear Stress Under Various Flow Conditions.

Cardiovascular diseases (CVDs) are the number one cause of death globally. Arterial endothelial cell (EC) dysfunction plays a key role in many of these CVDs, such as atherosclerosis. Blood flow-induced wall shear stress (WSS), among many other pathophysiological factors, is known to significantly contribute to EC dysfunction. The present study reports an in vitro investigation of the effect of quantified WSS on ECs, analyzing the EC morphometric parameters and cytoskeletal remodeling. The effects of four different flow cases (low steady laminar (LSL), medium steady laminar (MSL), nonzero-mean sinusoidal laminar (NZMSL), and laminar carotid (LCRD) waveforms) on the EC area, perimeter, shape index (SI), angle of orientation, F-actin bundle remodeling, and platelet endothelial cell adhesion molecule-1 (PECAM-1) localization were studied. For the first time, a flow facility was fully quantified for the uniformity of flow over ECs and for WSS determination (as opposed to relying on analytical equations). The SI and angle of orientation were found to be the most flow-sensitive morphometric parameters. A two-dimensional fast Fourier transform (2D FFT) based image processing technique was applied to analyze the F-actin directionality, and an alignment index (AI) was defined accordingly. Also, a significant peripheral loss of PECAM-1 in ECs subjected to atheroprone cases (LSL and NZMSL) with a high cell surface/cytoplasm stain of this protein is reported, which may shed light on of the mechanosensory role of PECAM-1 in mechanotransduction.

MRI and histopathologic study of a novel cholesterol-fed rabbit model of xanthogranuloma.

PURPOSE: To develop a rabbit model of xanthogranuloma based on supplementation of dietary cholesterol. The aim of this study was to analyze the xanthogranulomatous lesions using magnetic resonance imaging (MRI) and histological examination. MATERIALS AND METHODS: Rabbits were fed a low-level cholesterol (CH) diet (n = 10) or normal chow (n = 5) for 24 months. In vivo brain imaging was performed on a 3T MR system using fast imaging employing steady state acquisition, susceptibility-weighted imaging, spoiled gradient recalled, T1 -weighted inversion recovery imaging and T1 relaxometry, PD-weighted and T2 -weighted spin-echo imaging and T2 relaxometry, iterative decomposition of water and fat with echo asymmetry and least-squares estimation, ultrashort TE MRI (UTE-MRI), and T2* relaxometry. MR images were evaluated using a Likert scale for lesion presence and quantitative analysis of lesion size, ventricular volume, and T1 , T2 , and T2* values of lesions was performed. After imaging, brain specimens were examined using histological methods. RESULTS: In vivo MRI revealed that 6 of 10 CH-fed rabbits developed lesions in the choroid plexus. Region-of-interest analysis showed that for CH-fed rabbits the mean lesion volume was 8.5 ± 2.6 mm(3) and the volume of the lateral ventricle was significantly increased compared to controls (P < 0.01). The lesions showed significantly shorter mean T2 values (35 ± 12 msec, P < 0.001), longer mean T1 values (1581 ± 146 msec, P < 0.05), and shorter T2* values (22 ± 13 msec, P < 0.001) compared to adjacent brain structures. The ultrashort T2* components were visible using UTE-MRI. Histopathologic evaluation of lesions demonstrated features of human xanthogranuloma. CONCLUSION: Rabbits fed a low-level CH diet develop sizable intraventricular masses that have similar histopathological features as human xanthogranuloma. Multiparametric MRI techniques were able to provide information about the complex composition of these lesions. J. Magn. Reson. Imaging 2016;44:673-682.

Prevalence of dementia, heart disease and stroke in community-dwelling adults in Canada, 2016-2021: opportunities for joint prevention.

INTRODUCTION: This aim of this study is to provide updated estimates on the prevalence of dementia, heart disease, and stroke in Canadian communities. Targeting all three conditions together, at the community level, may be key to disease prevention and health aging in the Canadian population. METHODS: Using nationwide health survey data, we calculated the age-standardized prevalence of self-reported dementia, heart disease and stroke in adults aged 18 years and over residing in Canadian communities from 2016 to 2021. Poisson regression models were used to detect statistically significant changes in the prevalence of all three conditions from 2016 to 2021. RESULTS: Less than 1% (~ 175,000 individuals) of adults residing in Canadian communities reported dementia, 5% (~ 1.5 million individuals) reported heart disease, and more than 1% (~ 370,000 individuals) reported stroke annually from 2016 to 2021. Overall, the age-standardized prevalence for stroke decreased minimally from 2016 to 2021 (p = 0.0004). Although the age-standardized prevalence of heart disease and dementia decreased from 2016 to 2018, subsequent increases in prevalence from 2018 to 2021 led to a lack of overall statistically significant changes from 2016 to 2021 (p = 0.10 for heart disease and p = 0.37 for dementia). CONCLUSION: Recent increases in the prevalence of dementia, heart disease and stroke in Canadian communities threaten to reverse any gains in vascular disease prevention over the past six years. Findings reveal the urgent need for intensified prevention efforts that are community-based with a focus on joint reduction in the shared risk factors contributing to all three diseases.

Mimicking the biomolecular control of calcium oxalate monohydrate crystal growth: effect of contiguous glutamic acids.

Scanning confocal interference microscopy (SCIM) and molecular dynamics (MD) simulations were used to investigate the adsorption of the synthetic polypeptide poly(l-glutamic acid) (poly-glu) to calcium oxalate monohydrate (COM) crystals and its effect on COM formation. At low concentrations (1 µg/mL), poly-glu inhibits growth most effectively in ⟨001⟩ directions, indicating strong interactions of the polypeptide with {121} crystal faces. Growth in <010> directions was inhibited only marginally by 1 µg/mL poly-glu, while growth in <100> directions did not appear to be affected. This suggests that, at low concentrations, poly-glu inhibits lattice-ion addition to the faces of COM in the order {121} > {010} ≥ {100}. At high concentrations (6 µg/mL), poly-glu resulted in the formation of dumbbell-shaped crystals featuring concave troughs on the {100} faces. The effects on crystal growth indicate that, at high concentrations, poly-glu interacts with the faces of COM in the order {100} > {121} > {010}. This mirrors MD simulations, which predicted that poly-glu will adsorb to a {100} terrace plane (most calcium-rich) in preference to a {121} (oblique) riser plane but will adsorb to {121} riser plane in preference to an {010} terrace plane (least calcium-rich). The effects of different poly-glu concentration on COM growth (1-6 µg/mL) may be due to variations between the faces in terms of growth mechanism and/or (nano)roughness, which can affect surface energy. In addition, 1 µg/mL might not be adequate to reach the critical concentration for poly-glu to significantly pin step movement on {100} and {010} faces. Understanding the mechanisms involved in these processes is essential for the development of agents to reduce recurrence of kidney stone disease.

Perspectives of online anatomy teachers: A neglected study population struggles with the invisible student.

Online teachers are an under-researched population, but their perspectives are crucial to the successful implementation of online education. A fully online section of an established face-to-face (F2F) two-semester undergraduate anatomy course with a prosection laboratory commenced in 2012 at The University of Western Ontario, Canada. Professors' lectures for F2F students were broadcast in live and archived format to online students using Blackboard Collaborate (BBC) video conferencing software. Teaching assistants (TAs) delivered online laboratories using BBC and three-dimensional (3D) anatomical computer models. This study explored the common experiences and issues faced by the course teachers from 2012 to 2014. Transcripts from open-ended, individual interviews with professors (n = 4) and TAs (n = 5) were coded and analyzed thematically. The teachers' concern for their inability to see the students during sessions to assess class engagement and their teaching effectiveness, and to develop social relationships, was the main finding. However, video conferencing software and email were sufficient communication methods for the students' questions and the teachers' answers. The TAs noted usability challenges and anatomical inaccuracies in the 3D models compared to cadavers. Due to limitations of BBC's screen sharing function, live manipulation for the 3D computer models was not possible; however, the TAs found pedagogical value in using screen captures of the models for drawing activities with the students. Overall, preparation time for teaching online was longer than for F2F. The study's findings provide science educators with issues to consider when preparing for online teaching and recommendations to optimize the teaching experience.

Are Clerks Proficient in the Basic Sciences? Assessment of Third-Year Medical Students' Basic Science Knowledge Prior to and at the Completion of Core Clerkship Rotations.

Basic sciences are a cornerstone of undergraduate medical education (UME), yet research indicates that students' basic science knowledge is not well retained. Many UME curricula are increasing the integration between the basic and clinical sciences with the goal of enhancing students' knowledge levels; however, the impact of clerkship training on students' basic science knowledge remains inconclusive. Thus, using clerkship directors' expectations as framework, we aimed to assess third-year medical students' basic science knowledge during clerkship training and evaluate the influence of clerkship training on their basic science knowledge. Using concepts deemed necessary by clerkship directors, we created a basic science assessment for each clerkship rotation. Assessments were distributed to third-year medical students as a pre- and post-test to assess their basic science knowledge prior to and at the completion of each rotation. On average, students retained ≥ 60% of relevant basic science knowledge from pre-clerkship, and neither clerkship rotation order, nor the basic science discipline being assessed, impacted students' basic science knowledge levels. Post-test data revealed that students, on average, reinforced fundamental concepts during clerkship. Interestingly, even though lower-performing students demonstrated the greatest post-test improvement, they still left each rotation with knowledge deficits compared with their highest-performing peers, suggesting that the clinical experience of clerkship appears to be particularly beneficial for lower-performing students, in regard to enhancing their basic science knowledge. Overall, results indicate that earlier exposure to clinical learning in UME, along with integration of basic science education into clerkship, could promote students' basic science knowledge acquisition and retention.

Correction to: Are Clerks Proficient in the Basic Sciences? Assessment of Third-Year Medical Students' Basic Science Knowledge Prior to and at the Completion of Core Clerkship Rotations.

[This corrects the article DOI: 10.1007/s40670-021-01249-3.].

Enzyme-sensitive magnetic resonance imaging targeting myeloperoxidase identifies active inflammation in experimental rabbit atherosclerotic plaques.

BACKGROUND: Inflammation undermines the stability of atherosclerotic plaques, rendering them susceptible to acute rupture, the cataclysmic event that underlies clinical expression of this disease. Myeloperoxidase is a central inflammatory enzyme secreted by activated macrophages and is involved in multiple stages of plaque destabilization and patient outcome. We report here that a unique functional in vivo magnetic resonance agent can visualize myeloperoxidase activity in atherosclerotic plaques in a rabbit model. METHODS AND RESULTS: We performed magnetic resonance imaging of the thoracic aorta of New Zealand White rabbits fed a cholesterol (n=14) or normal (n=4) diet up to 2 hours after injection of the myeloperoxidase sensor bis-5HT-DTPA(Gd) [MPO(Gd)], the conventional agent DTPA(Gd), or an MPO(Gd) analog, bis-tyr-DTPA(Gd), as controls. Delayed MPO(Gd) images (2 hours after injection) showed focal areas of increased contrast (>2-fold) in diseased wall but not in normal wall (P=0.84) compared with both DTPA(Gd) (n=11; P<0.001) and bis-tyr-DTPA(Gd) (n=3; P<0.05). Biochemical assays confirmed that diseased wall possessed 3-fold elevated myeloperoxidase activity compared with normal wall (P<0.01). Areas detected by MPO(Gd) imaging colocalized and correlated with myeloperoxidase-rich areas infiltrated by macrophages on histopathological evaluations (r=0.91, P<0.0001). Although macrophages were the main source of myeloperoxidase, not all macrophages secreted myeloperoxidase, which suggests that distinct subpopulations contribute differently to atherogenesis and supports our functional approach. CONCLUSIONS: The present study represents a unique approach in the detection of inflammation in atherosclerotic plaques by examining macrophage function and the activity of an effector enzyme to noninvasively provide both anatomic and functional information in vivo.

Early identification of aortic valve sclerosis using iron oxide enhanced MRI.

PURPOSE: To test the ability of MION-47 enhanced MRI to identify tissue macrophage infiltration in a rabbit model of aortic valve sclerosis (AVS). MATERIALS AND METHODS: The aortic valves of control and cholesterol-fed New Zealand White rabbits were imaged in vivo pre- and 48 h post-intravenous administration of MION-47 using a 1.5 Tesla (T) MR clinical scanner and a CINE fSPGR sequence. MION-47 aortic valve cusps were imaged ex vivo on a 3.0T whole-body MR system with a custom gradient insert coil and a three-dimensional (3D) FIESTA sequence and compared with aortic valve cusps from control and cholesterol-fed contrast-free rabbits. Histopathological analysis was performed to determine the site of iron oxide uptake. RESULTS: MION-47 enhanced the visibility of both control and cholesterol-fed rabbit valves in in vivo images. Ex vivo image analysis confirmed the presence of significant signal voids in contrast-administered aortic valves. Signal voids were not observed in contrast-free valve cusps. In MION-47 administered rabbits, histopathological analysis revealed iron staining not only in fibrosal macrophages of cholesterol-fed valves but also in myofibroblasts from control and cholesterol-fed valves. CONCLUSION: Although iron oxide labeling of macrophage infiltration in AVS has the potential to detect the disease process early, a macrophage-specific iron compound rather than passive targeting may be required.

Clinical field-strength MRI of amyloid plaques induced by low-level cholesterol feeding in rabbits.

Two significant barriers have limited the development of effective treatment of Alzheimer's disease. First, for many cases the aetiology is unknown and likely multi-factorial. Among these factors, hypercholesterolemia is a known risk predictor and has been linked to the formation of beta-amyloid plaques, a pathological hallmark this disease. Second, standardized diagnostic tools are unable to definitively diagnose this disease prior to death; hence new diagnostic tools are urgently needed. Magnetic resonance imaging (MRI) using high field-strength scanners has shown promise for direct visualization of beta-amyloid plaques, allowing in vivo longitudinal tracking of disease progression in mouse models. Here, we present a new rabbit model for studying the relationship between cholesterol and Alzheimer's disease development and new tools for direct visualization of beta-amyloid plaques using clinical field-strength MRI. New Zealand white rabbits were fed either a low-level (0.125-0.25% w/w) cholesterol diet (n = 5) or normal chow (n = 4) for 27 months. High-resolution (66 x 66 x 100 microm(3); scan time = 96 min) ex vivo MRI of brains was performed using a 3-Tesla (T) MR scanner interfaced with customized gradient and radiofrequency coils. Beta-amyloid-42 immunostaining and Prussian blue iron staining were performed on brain sections and MR and histological images were manually registered. MRI revealed distinct signal voids throughout the brains of cholesterol-fed rabbits, whereas minimal voids were seen in control rabbit brains. These voids corresponded directly to small clusters of extracellular beta-amyloid-positive plaques, which were consistently identified as iron-loaded (the presumed source of MR contrast). Plaques were typically located in the hippocampus, parahippocampal gyrus, striatum, hypothalamus and thalamus. Quantitative analysis of the number of histologically positive beta-amyloid plaques (P < 0.0001) and MR-positive signal voids (P < 0.05) found in cholesterol-fed and control rabbit brains corroborated our qualitative observations. In conclusion, long-term, low-level cholesterol feeding was sufficient to promote the formation of extracellular beta-amyloid plaque formation in rabbits, supporting the integral role of cholesterol in the aetiology of Alzheimer's disease. We also present the first evidence that MRI is capable of detecting iron-associated beta-amyloid plaques in a rabbit model of Alzheimer's disease and have advanced the sensitivity of MRI for plaque detection to a new level, allowing clinical field-strength scanners to be employed. We believe extension of these technologies to an in vivo setting in rabbits is feasible and that our results support future work exploring the role of MRI as a leading imaging tool for this debilitating and life-threatening disease.

Expectations and Perceptions of Students' Basic Science Knowledge: Through the Lens of Clerkship Directors.

Basic sciences are a cornerstone of undergraduate medical education (UME) as they provide a necessary foundation for the clinical sciences to be built upon and help foster trainees' competency. However, research indicates that students' basic science knowledge is not well retained, and as a result, students are ill-prepared, with respect to their basic science knowledge, when entering clerkship. One potential reason why students may not be prepared for clerkship is a lack of understanding as to which basic science concepts are critical for medical students to retain from pre-clerkship. We facilitated interviews with all core UME clerkship directors to establish which basic science concepts they expect students to know prior to each clerkship rotation, along with student's basic science strengths and areas of improvement. Interviews revealed that students are expected to have some knowledge of every basic science prior to clerkship, with pharmacology being a strong focus, as many specialties deal with common drugs and classes of drugs. Additionally, general anatomy and physiology knowledge were deemed student strengths in two rotations. Clerkship directors focused on perceived areas of improvement more than perceived strengths, with the most prevalent areas being pharmacology, microbiology, and detailed anatomy. These results represent views of clerkship directors from one Canadian institution; however, since clerks rotate through institutions across Canada, this data provides the impetus for creating a national discussion to help foster standardization of UME curricula, with the overarching goal of ensuring all graduates are proficient in the necessary fundamentals as they transition into residency.

Close Association of Myeloperoxidase-Producing Activated Microglia with Amyloid Plaques in Hypercholesterolemic Rabbits.

Microglial activation and oxidative stress have been linked to the formation of amyloid plaques found in Alzheimer's disease (AD). Epidemiologic and experimental evidence also suggests that cholesterol (CH) contributes to the pathogenesis of AD, particularly the formation of amyloid plaques. We have previously described the development of amyloid-ß (Aß) plaques in New Zealand white rabbits maintained on a 0.125%-0.25% w/w CH diet for extended periods of time (28 months). Here we further characterize this model with combined immunofluorescence and immunohistochemical staining to evaluate markers of immune cell activation. Five out of eight CH-fed rabbits, but not control rabbits, developed extracellular Aß plaques in both the hippocampus and cortex. Significantly (p < 0.05) higher CD11b microglial staining was found in the hippocampus, temporal cortex, and frontal cortex of CH-fed versus control rabbits. In the temporal cortex and parietal cortex, active CD-11b- and ferritin-positive microglia were found in close proximity to Aß plaques. Classification and quantification of activated microglia in the temporal cortex showed that 68±12.9%, 25±7.3%, and 7±2.7% of all microglia had a primed, reactive, and amoeboid phenotype, respectively. Activated microglia also expressed myeloperoxidase which was co-localized to amyloid deposits. Our findings in this dietary-based model lend further support of a role of activated microglia and oxidative stress during the development of AD and strengthens the links between hypercholesterolemia, inflammatory status, and AD.

Improving Online Interactions: Lessons from an Online Anatomy Course with a Laboratory for Undergraduate Students.

An online section of a face-to-face (F2F) undergraduate (bachelor's level) anatomy course with a prosection laboratory was offered in 2013-2014. Lectures for F2F students (353) were broadcast to online students (138) using Blackboard Collaborate (BBC) virtual classroom. Online laboratories were offered using BBC and three-dimensional (3D) anatomical computer models. This iteration of the course was modified from the previous year to improve online student-teacher and student-student interactions. Students were divided into laboratory groups that rotated through virtual breakout rooms, giving them the opportunity to interact with three instructors. The objectives were to assess student performance outcomes, perceptions of student-teacher and student-student interactions, methods of peer interaction, and helpfulness of the 3D computer models. Final grades were statistically identical between the online and F2F groups. There were strong, positive correlations between incoming grade average and final anatomy grade in both groups, suggesting prior academic performance, and not delivery format, predicts anatomy grades. Quantitative student perception surveys (273 F2F; 101 online) revealed that both groups agreed they were engaged by teachers, could interact socially with teachers and peers, and ask them questions in both the lecture and laboratory sessions, though agreement was significantly greater for the F2F students in most comparisons. The most common methods of peer communication were texting, Facebook, and meeting F2F. The perceived helpfulness of the 3D computer models improved from the previous year. While virtual breakout rooms can be used to adequately replace traditional prosection laboratories and improve interactions, they are not equivalent to F2F laboratories.

In Vivo MRI of Amyloid Plaques in a Cholesterol-Fed Rabbit Model of Alzheimer's Disease.

Hypercholesterolemia has been identified as a risk factor for Alzheimer's disease. In this study, rabbits were fed either a cholesterol diet or normal chow diet for 24 months. At endpoint, in vivo MRI was performed at the field strength of 3 Tesla using fast imaging employing steady state acquisition without (FIESTA) or with susceptibility-weighted post-processing (SWI-FIESTA) and susceptibility-weighted imaging with multi-echo acquisition (SWAN). This imaging revealed signal voids/hypointensities throughout the cortex, sub-cortex, and hippocampus of cholesterol-fed animals compared to control animals. Quantitative image analysis corroborated these qualitative findings and highlighted that SWI processing of FIESTA images significantly improved the detectability of plaques (p < 0.05). Aß immunostaining and Prussian blue staining for iron demonstrated that the voids in MR images corresponded to iron-laden Aß-positive plaques. This study demonstrates non-invasive in vivo visualization of Aß plaques in a diet-induced large animal model of Alzheimer's disease. This work lays the foundation for future work focusing on longitudinal monitoring of plaque formation in this model and the effects of diet or drug interventions.

Control of calcium oxalate crystal growth by face-specific adsorption of an osteopontin phosphopeptide.

Mineral-associated proteins have been proposed to regulate many aspects of biomineralization, including the location, type, orientation, shape, and texture of crystals. To understand how proteins achieve this exquisite level of control, we are studying the interaction between the phosphoprotein osteopontin (OPN) and the biomineral calcium oxalate monohydrate (COM). In the present study, we have synthesized peptides corresponding to amino acids 220-235 of rat bone OPN (pSHEpSTEQSDAIDpSAEK), one of several highly phosphorylated, aspartic-, and glutamic acid-rich sequences found in the protein. To investigate the role of phosphorylation in interaction with crystals, peptides containing no (P0), one (P1), or all three (P3) phosphates were prepared. Using a novel combination of confocal microscopy and scanning electron microscopy, we show that these peptides adsorb preferentially to {100} faces of COM and inhibit growth of these faces in a phosphorylation-dependent manner. To characterize the mechanism of adsorption of OPN peptides to COM, we have performed the first atomic-scale molecular-dynamics simulation of a protein-crystal interaction. P3 adsorbs to the {100} face much more rapidly than P1, which in turn adsorbs more rapidly than P0. In all cases, aspartic and glutamic acid, not phosphoserine, are the amino acids in closest contact with the crystal surface. These studies have identified a COM face-specific adsorption motif in OPN and delineated separate roles for carboxylate and phosphate groups in inhibition of crystal growth by mineral-associated phosphoproteins. We propose that the formation of close-range, stable, and face-specific interactions is a key factor in the ability of phosphoproteins to regulate biomineralization processes.

The skeletons in our closet: E-learning tools and what happens when one side does not fit all.

In the anatomical sciences, e-learning tools have become a critical component of teaching anatomy when physical space and cadaveric resources are limited. However, studies that use empirical evidence to compare their efficacy to visual-kinesthetic learning modalities are scarce. The study examined how a visual-kinesthetic experience, involving a physical skeleton, impacts learning when compared with virtual manipulation of a simple two-dimensional (2D) e-learning tool, A.D.A.M. Interactive Anatomy. Students from The University of Western Ontario, Canada (n = 77) participated in a dual-task study to: (1) investigate if a dual-task paradigm is an effective tool for measuring cognitive load across these different learning modalities; and (2) to assess the impact of knowledge recall and spatial ability when using them. Students were assessed using knowledge scores, Stroop task reaction times, and mental rotation test scores. Results demonstrated that the dual-task paradigm was not an effective tool for measuring cognitive load across different learning modalities with respect to kinesthetic learning. However, our study highlighted that handing physical specimens yielded major, positive impacts on performance that a simple commercial e-learning tool failed to deliver (P < 0.001). Furthermore, students with low spatial ability were significantly disadvantaged when they studied the bony joint and were tested on contralateral images (P = 0.046, R = 0.326). This suggests that, despite limbs being mirror images, students should be taught the anatomy of, as well as procedures on, both sides of the human body, enhancing the ability of all students, regardless of spatial ability, to take anatomical knowledge into the clinic and perform successfully. Anat Sci Educ 10: 570-588. © 2017 American Association of Anatomists.

Academic nightmares: Predatory publishing.

Academic researchers who seek to publish their work are confronted daily with a barrage of e-mails from aggressive marketing campaigns that solicit them to publish their research with a specialized, often newly launched, journal. Known as predatory journals, they often promise high editorial and publishing standards, yet their exploitive business models, poor quality control, and minimal overall transparency victimize those researchers with limited academic experience and pave the way for low-quality articles that threaten the foundation of evidence-based research. Understanding how to identify these predatory journals requires thorough due diligence on the part of the submitting authors, and a commitment by reputable publishers, institutions, and researchers to publicly identify these predators and eliminate them as a threat to the careers of young scientists seeking to disseminate their work in scholarly journals. Anat Sci Educ 10: 392-394. © 2016 American Association of Anatomists.

Educational software usability: Artifact or Design?

Online educational technologies and e-learning tools are providing new opportunities for students to learn worldwide, and they continue to play an important role in anatomical sciences education. Yet, as we shift to teaching online, particularly within the anatomical sciences, it has become apparent that e-learning tool success is based on more than just user satisfaction and preliminary learning outcomes-rather it is a multidimensional construct that should be addressed from an integrated perspective. The efficiency, effectiveness and satisfaction with which a user can navigate an e-learning tool is known as usability, and represents a construct which we propose can be used to quantitatively evaluate e-learning tool success. To assess the usability of an e-learning tool, usability testing should be employed during the design and development phases (i.e., prior to its release to users) as well as during its delivery (i.e., following its release to users). However, both the commercial educational software industry and individual academic developers in the anatomical sciences have overlooked the added value of additional usability testing. Reducing learner frustration and anxiety during e-learning tool use is essential in ensuring e-learning tool success, and will require a commitment on the part of the developers to engage in usability testing during all stages of an e-learning tool's life cycle. Anat Sci Educ 10: 190-199. © 2016 American Association of Anatomists.

Radial artery as an autologous cell source for valvular tissue engineering efforts.

To create a viable tissue-engineered aortic valve, it is important to identify suitable autologous cell sources that may be seeded onto a biocompatible scaffold. This study focused on the radial artery (RA) as one possible source, investigated optimal culture conditions, and determined the usefulness of small intestinal submucosa (SIS) as a scaffold for tissue-engineering. Porcine RA cells were cultured on either two-dimensional (2D) 100-mm dishes or three-dimensional (3D) 1-cm(2) SIS sheets, producing cell-scaffold composites (CSCs). Both 2D and 3D cultures were maintained in either Medium 199 (M199) or endothelial growth media (EGM) to determine optimal growth conditions. Cellular phenotype and matrix metalloproteinase (MMP) profiles were determined by immunoblotting of cell lysates and zymography of conditioned media, respectively. Cellular invasion was analyzed immunohistochemically on CSC tissue sections. We show that the RA contains phenotypes consistent with those found in the normal aortic valve. EGM, compared with M199, promotes the invasion and remodeling of SIS by RA cells, which is crucial in the process of replacing the foreign tissue scaffold prior to implantation. To our knowledge, this is the first study to show that the RA is a suitable source for the generation of a tissue-engineered valve.