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Introduction: The coronavirus disease 2019 (COVID-19) pandemic has increased the use of technology for communication including departmental conferences, working remotely, and distance teaching. Methods to enable these activities should be developed and promulgated. Objective: To repurpose a preexisting educational website to enable the development of a COVID-19 autopsy biorepository to support distance teaching and COVID-19 research. Methods: After consent was obtained, autopsies were performed on patients with a confirmed positive severe acute respiratory syndrome coronavirus-2 reverse-transcriptase-polymerase-chain reaction test. Autopsies were performed according to a COVID-19 protocol, and all patients underwent both gross and microscopic examination. The H and E histology slides were scanned using a Leica Biosystems Aperio CS ScanScope whole slide scanner and the digital slide files were converted to deep zoom images that could be uploaded to the University of Alabama at Birmingham (UAB) Pathology Educational Instructional Resource website where virtual microscopy of the slides is available. Results: A total of 551 autopsy slides from 24 UAB COVID-19 cases, 1 influenza H1N1 case and 1 tuberculosis case were scanned and uploaded. Five separate COVID-19 research teams used the digital slides remotely with or without a pathologist on a Zoom call. The scanned slides were used to produce one published case report and one published research project. The digital COVID-19 autopsy biorepository was routinely used for educational conferences and research meetings locally, nationally and internationally. Conclusion: The repurposing of a pre-existing website enabled telepathology consultation for research and education purposes. Combined with other communication technology (Zoom) this achievement highlights what is possible using pre-existing technologies during a global pandemic.

Context.—This review chronicles the establishment of a clinical laboratory in Cleveland Clinic Abu Dhabi, a greenfield tertiary/quaternary care hospital in the United Arab Emirates. It discusses the challenges faced, solutions sought, and lessons learned and shares insights and pitfalls that may be encountered in such an undertaking.Objectives.—To share our experience in building a clinical laboratory in a start-up, multispecialty hospital and how we provided support and managed people, processes, and technology for building and making operational the Cleveland Clinic Abu Dhabi.Data Sources.—The Medline (PubMed, National Center for Biotechnology Information, Bethesda, Maryland) database was used to review this topic as well as other journals, books, and Google (Mountain View, California) search engine.Conclusions.—To deliver on the promise of quality healthcare in a culturally appropriate setting close to home, Cleveland Clinic Abu Dhabi proved to be an unprecedented and ambitious project, jointly carried out by Mubadala Investment Corporation and the Cleveland Clinic Foundation. Cognizant of the scale of this task, hospital leadership engaged closely with staff and stakeholders through motivational techniques and effective communication. Excellent project planning and execution of complex tasks were required for initiation of services. Establishing the clinical laboratory served as an instructive model in fostering multidisciplinary teamwork by highlighting ways to manage operational roadblocks and opportunities in the planning, commissioning, and activation phases. Throughout the activation process, all efforts were directed to create a patient-safety culture within an intentional-learning organization.

Context.—The health care industry is growing rapidly and is continually seeking more-innovative ways to deliver patient care. The growing demands of clinicians seeking faster and more-efficient ways of providing care to their patients presents challenges to clinical laboratory services. Point-of-care testing (POCT) is frequently seen as a viable solution to address this dilemma. The role of POCT is widely established and accepted in many circumstances provided certain criteria are met.Objectives.—To discuss the Cleveland Clinic Abu Dhabi experience—the challenges faced and the solutions found—during the process of establishing a POCT service in a greenfield hospital, and to share this experience to support health care professionals wishing to establish or expand POCT services.Data Source.—First-hand expert opinion relating to setting up a POCT service, which was guided and informed by national and international standards and regulatory bodies, provide the basis for this review.Conclusions.—Point-of-care testing is a fast growing and unique discipline of pathology. The establishment of a new POCT service creates distinctive and unique challenges compared with traditional laboratory services. The difficulties experienced are compounded in a greenfield hospital but the process of multidisciplinary collaboration and information exchange among peer groups allows the efficient development of a highly effective POCT department.

Context.—Opening a new hospital is a once in a lifetime experience and can be very inspiring for those involved in its activation. However, establishing a safe transfusion practice in a greenfield environment comes with unique challenges and opportunities.Objective.—To highlight critical activation components such as on-boarding of new personnel, establishing clinical practices, and integrating critical laboratory software.Design.—Our staff initially faced challenges in standardizing transfusion medicine clinical practice inside the laboratory. Our efforts were mainly focused on the appropriate use of various transfusion orders, creating comprehensive policies for type and screening, cost effective utilization of blood products, and establishment of the maximum surgical blood order schedule. The transfusion service was launched with 2 information technology programs that separately facilitated steps in the transfusion process, but did not provide centralized access to the entire process. In these circumstances, we partnered with the laboratory information system team to create a series of interfaces that streamlined each system's functionality and implemented the existing infrastructure with upgrades that enable remote location and management of blood products.Results.—The transfusion medicine team spent more than a year training and monitoring workflows to avoid individual variations between technologists and to adopt our own standards of practice. Participation in a structured training plan was also necessary between clinical caregivers to know the safe and efficient use of these standards.Conclusions.—Although laboratory and clinical staff are knowledgeable in care delivery, it is always a learning experience to establish a new system because of the natural tendency of resorting to previous practices and resistance to new approaches.

The popularity of vascular stents continues to increase for a variety of applications, including coronary, lower limb, renal, carotid, and neurovascular disorders. However, their clinical effectiveness is hindered by numerous postdeployment complications, which may stimulate inflammatory and fibrotic reactions. The purpose of this study was to evaluate the vessel inflammatory response via in vivo imaging in a mouse stent implantation model. Corroded and noncorroded self-expanding miniature nitinol stents were implanted in mice abdominal aortas, and novel in vivo imaging techniques were used to assess trafficking and accumulation of fluorescent donor monocytes as well as cellular proliferation at the implantation site. Monocytes were quantitatively tracked in vivo and found to rapidly clear from circulation within hours after injection. Differences were found between the test groups with respect to the numbers of recruited monocytes and the intensity of the resulting fluorescent signal. Image analysis also revealed a subtle increase in matrix metalloproteinase activity in corroded compared with the normal stented aortas. In conclusion, this study has been successful in developing a murine stent inflammation model and applying novel in vivo imaging tools and methods to monitor the complex biological processes of the host vascular wall response.

Context.—This review examines challenges and opportunities in preparing laboratories in a startup phase for accreditation by both the College of American Pathologists (CAP) and International Organization for Standardization (ISO) 15189 in an international setting as it relates to our experience at Cleveland Clinic Abu Dhabi Laboratory. It also discusses some of the strategies used in executing those projects and the added advantages in pursuing both types of accreditations.Objectives.—To share our experience with CAP and ISO 15189 accreditations in a startup international operation in relation to the challenges encountered and implementation strategy success factors.Data Sources.—MEDLINE (PubMed) database was used to review this topic as well as peer-reviewed articles and World Health Organization publications on the topic.Conclusions.—Accreditation is a perfect means toward building quality medical laboratories in a diverse workforce environment and improving patient safety. Further, it establishes a strong foundation on which any new operation can build a sustainable quality improvement culture. Accreditations by CAP and/or ISO are among the most reputable and well-established accreditation systems that clinical laboratories could aim for. As a result of both accreditations offering synergistic and complementing features, we recommend that any laboratory seeking excellence in quality and performance should consider exploring both. Key elements to success include having dedicated project management and change management support while preparing for accreditation. Laboratories seeking accreditation in early operational stages may face a number of challenges; however, significant opportunities will also be present to optimize various operational components from the beginning.

Preliminary studies have revealed that some stents undergo corrosion and fatigue-induced fracture in vivo, with significant release of metallic ions into surrounding tissues. A direct link between corrosion and in-stent restenosis has not been clearly established; nonetheless in vitro studies have shown that relatively high concentrations of heavy metal ions can stimulate both inflammatory and fibrotic reactions, which are the main steps in the process of restenosis. To isolate the mechanical effects from the local biochemical effects, accelerated biomechanical testing was performed on single and overlapping Nickel-Titanium (NiTi) stents subjected to various degrees of curvature. Post testing, stents were evaluated using Scanning Electron Microscopy (SEM) to identify the type of surface alterations. Fretting wear was observed in overlapping cases, in both straight and curved configurations. Stent strut fractures occurred in the presence of geometric curvature. Fretting wear and fatigue fractures observed on stents following mechanical simulation were similar to those from previously reported human stent explants. It has been shown that biomechanical factors such as arterial curvature combined with stent overlapping enhance the incidence and degree of wear and fatigue fracture when compared to single stents in a straight tube configuration. In Press

Objective— Clinical and experimental studies demonstrate the important roles of vascular smooth muscle cells (VSMC) in the pathogenesis of atherosclerosis. We have previously determined that the osteogenic transcription factor Runx2 is essential for VSMC calcification. The present study characterized Runx2-regulated signals and their potential roles in vascular calcification. Methods and Results— In vivo studies with atherogenic apolipoprotein E −/− mice demonstrated that increased oxidative stress was associated with upregulation of Runx2 and receptor activator of nuclear factor κB ligand (RANKL), which colocalized in the calcified atherosclerotic lesions and were juxtaposed to infiltrated macrophages and osteoclast-like cells that are positively stained for an osteoclast marker, tartrate-resistant acid phosphatase. Mechanistic studies using RNA interference, a luciferase reporter system, chromatin immunoprecipitation, and electrophoretic mobility shift assays indicated that Runx2 regulated the expression of RANKL via a direct binding to the 5′-flanking region of the RANKL. Functional characterization revealed that RANKL did not induce VSMC calcification, nor was RANKL required for oxidative stress–induced VSMC calcification. Using a coculture system, we demonstrated that VSMC-expressed RANKL induced migration as well as differentiation of bone marrow-derived macrophages into multinucleated, tartrate-resistant acid phosphatase–positive osteoclast-like cells. These effects were inhibited by the RANKL antagonist osteoprotegerin and with VSMC deficient in Runx2 or RANKL. Conclusion— We demonstrate that Runx2 directly binds to the promoter and controls the expression of RANKL, which mediates the crosstalk between calcifying VSMC and migration and differentiation of macrophages into osteoclast-like cells in the atherosclerotic lesions. Our studies provide novel mechanistic insights into the regulation and function of VSMC-derived RANKL in the pathogenesis of atherosclerosis and vascular calcification.

Cardiovascular disease is the number one cause of death in the United States. Deployment of stents and vascular grafts has been a major therapeutic method for treatment. However, restenosis, incomplete endothelialization, and thrombosis hamper the long term clinical success. As a solution to meet these current challenges, we have developed a native endothelial ECM mimicking self-assembled nanofibrous matrix to serve as a new treatment model. The nanofibrous matrix is formed by self-assembly of peptide amphiphiles (PAs), which contain nitric oxide (NO) donating residues, endothelial cell adhesive ligands composed of YIGSR peptide sequence, and enzyme-mediated degradable sites. NO was successfully released from the nanofibrous matrix rapidly within 48 hours, followed by sustained release over period of 30 days. The NO releasing nanofibrous matrix demonstrated a significantly enhanced proliferation of endothelial cells (51 ± 3 % to 67 ± 2 %) but reduced proliferation of smooth muscle cells (35 ± 2 % to 16 ± 3 %) after 48 hrs of incubation. There was also a 150-fold decrease in platelet attachment on the NO releasing nanofibrous matrix (470 ± 220 platelets/cm2) compared to the collagen-I (73 ± 22 × 103 platelets/cm2) coated surface. The nanofibrous matrix has the potential to be applied to various cardiovascular implants as a self-assembled coating, thereby providing a native endothelial extracellular matrix (ECM) mimicking environment.

The popularity of vascular stents continues to increase for a variety of applications, including coronary, lower limb, renal, carotid, and neurovascular disorders. However, their clinical effectiveness is hindered by numerous postdeployment complications, which may stimulate inflammatory and fibrotic reactions. The purpose of this study was to evaluate the vessel inflammatory response via in vivo imaging in a mouse stent implantation model. Corroded and noncorroded self-expanding miniature nitinol stents were implanted in mice abdominal aortas, and novel in vivo imaging techniques were used to assess trafficking and accumulation of fluorescent donor monocytes as well as cellular proliferation at the implantation site. Monocytes were quantitatively tracked in vivo and found to rapidly clear from circulation within hours after injection. Differences were found between the test groups with respect to the numbers of recruited monocytes and the intensity of the resulting fluorescent signal. Image analysis also revealed a subtle increase in matrix metalloproteinase activity in corroded compared with the normal stented aortas. In conclusion, this study has been successful in developing a murine stent inflammation model and applying novel in vivo imaging tools and methods to monitor the complex biological processes of the host vascular wall response.

This paper aims to explore some properties of certain third-order linear sequences which have some properties analogous to the better known second-order sequences of Fibonacci and Lucas. Historical background issues are outlined. These, together with the number and combinatorial theoretical results, provide plenty of pedagogical opportunities for further development.

A study has been carried out on the effect of the optical density of inks on the specular reflectance of a printed surface. Samples of cyan, magenta, and yellow ink were printed with a liquid electrophotographic, an offset lithographic, and a thermal transfer printer. Specular reflectance was measured using a goniophotometric instrument to produce the bidirectional reflectance distribution function. The results clearly demonstrated that the amount of specular light reflected from a printed surface depends strongly on the optical density of the ink. A linear correlation was observed between the total amount of specular light reflected from the surface and the square of the transmittance of the ink layer. A highly transparent ink (e.g., yellow ink measured with red light) reflected approximately twice as much specular light than a highly absorbing ink (e.g., yellow with blue or cyan with red). It is suggested that specular reflections from surfaces below the ink layer can contribute significantly to overall specular reflectance of a printed image.