1,720,985 research outputs found
Cellular Therapy for Saccular Intracranial Aneurysms: A Proof-of-Concept Study
No full textIntracranial aneurysms are pathological dilations of arteries in the brain. Rupture of an aneurysm would be catastrophic, resulting in death in half of the cases and permanent neu- rological deficits in half of the survivors. The current standard-of-care for treating aneurysms is endovascular coiling, a procedure that involves packing the aneurysm with soft platinum- made coils that cause the blood within the aneurysm to clot, consequently slowing the flow of blood into the aneurysm. This is followed by a healing response that remodels the clot into fibrous tissue and regenerates a neointima layer that covers the neck of the aneurysm and isolates it from the parent vessel. Lack of proper healing in about one-fifth of the patients results in recurrence of the aneurysm. Building on a growing body of literature, this project evaluated the potential therapeutic effects of mesenchymal stem/stromal cells (MSCs) on the healing of coiled aneurysms in a rabbit model.2 year
Mesenchymal Progenitors in the Epidural Fat and Dura Mater Participate in Tissue Homeostasis and Wound Healing
No full textMesenchymal progenitor cells (MPCs) are adult cells capable of self-renewal and differentiation into cells that make up mesodermal tissues such as bone, cartilage, and fat. MPCs are believed to play a significant role in tissue maintenance and repair. MPCs are present in many adult connective tissues but are typically found in higher quantities in adipose tissues for yet unknown reasons. Recently, our research group identified MPC populations within epidural fat and the adjacent dura mater. Clinically, epidural fat is frequently considered a space-filling, biologically inert tissue; therefore, it is common practice for spine surgeons to discard it during surgical procedures. As the development and cellular origins of both epidural fat and the dura mater remain unclear, I hypothesized that epidural fat MPCs contribute to the maintenance of dural integrity throughout growth and post-injury. Using Paired related homeobox 1 (Prx1) and Hypermethylated in cancer 1 (Hic1) transgenic lineage tracing mice, the localization of epidural fat MPCs were identified during normal maturation and at skeletal maturity. This lineage tracing revealed an overlap between Prx1+ and Hic1+ populations, indicating a potential hierarchical relationship between the two MPC populations. When Prx1+/ Hic1+ MPCs were ablated, the expression of the dural marker α-SMA was lost in adjacent dura mater suggesting these cells are required for tissue homeostasis. Both MPC populations were observed to respond to dural injuries by homing to the lesion site. The process by which epidural fat MPCs maintain the dura mater through growth and after injury was accelerated in p21-/- mice (known for increased tissue regeneration/ cell proliferation). While MPCs have been identified and characterized in other adipose tissues, the role in epidural fat remained elusive. This study contributed to our knowledge of the role of epidural fat MPCs in vivo in aspects of growth, homeostasis, and repair of dural tissue. This thesis emphasizes the importance of revisiting the prevalent notion of epidural fat as biologically insignificant and the process of discarding it during surgery
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
A modified footplate for the Kerrison rongeur
No full textUse of the Kerrison rongeur for bone removal in spinal surgery is associated with dural tears and cerebrospinal fluid (CSF) leaks. We report a modification of the Kerrison rongeur footplate designed to reduce the risk of dural tears. A novel footplate was designed by incorporating the following parameters: (1) tapering the footplate to deflect soft tissue downward during positioning of the rongeur underneath the bone, and (2) making the footplate longer and wider than the cutting element to prevent soft tissue from entering into the cutting surface. Stereolithography models of the modified footplate were made and tested in a cadaver. A stainless steel modified footplate was then incorporated into an existing Kerrison rongeur as a working prototype, and tested in 20 laminectomy cases to clinically validate its design. The modified footplate prevented soft tissue from entering the cutting surface of the Kerrison rongeur in the manner intended by its design. No dural tears or CSF leaks were encountered in any instance. Potential soft tissue compression caused by an increase in footplate dimensions was not a significant issue in the rongeur size tested. This modification, however, might not be practical in rongeurs larger than 3 mm. The risk of dural tears and cerebrospinal fluid leaks in spinal surgery may be reduced by this footplate modification of the Kerrison rongeur. Soft tissue compression may limit the incorporation of this modification to rongeurs of 3 mm or smaller. The promising results warrant further tests with a wider range of sizes.Center for Integration of Medicine and Innovative Technology (U.S. Army Medical Research Acquisition Activity Cooperative Agreement No. DAMD17-02-2-0006
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Enhancing Cardiac Repair using Matrix Biomaterials via Epicardial Implantation and Pericardial Injection
No full textIschemic heart disease and subsequent pathologic ventricular remodeling is a common cause of end-stage heart failure, accounting for 38% of cardiac transplantations worldwide. After myocardial infarction, fibrosis dominates cardiac healing and pathologic myocardial remodeling, replacing ischemic and injured muscle with minimally-contractile scar. Shifting remodeling pathways to favor angiogenesis may be a more adaptive tissue healing response whereby the formation of new blood vessels can recover ischemic myocardium. Extracellular matrix biomaterials provide a factor-rich microenvironment capable of modulating cellular activity. Our group has previously demonstrated that a decellularized biomaterial derived from porcine small intestinal submucosal extracellular matrix (SIS-ECM) modulates human cardiac fibroblast activity to mitigate fibrotic pathways and upregulate angiogenic paracrine activity. Subsequently, our past work demonstrates that epicardial application of SIS-ECM improves cardiac function in rat and porcine infarct models. Along with fibroblast modulation, recent studies have identified specific immune cell populations that play key roles in tissue angiogenesis and optimization of cardiac healing after myocardial infarction. As such, we investigated the immunomodulatory properties of SIS-ECM and underlying cellular pathways. First, we investigated biomaterial-mediated cardiac immune modulation with epicardial implantation of SIS-ECM in a small animal infarct model. Our proof-of-concept study showed that suturing the bioactive matrix as a patch over infarcted muscle upregulates counts of pro-inflammatory and pro-angiogenic immune cells in the myocardium on flow cytometry. Using resonant confocal microscopy, fibroblasts were identified to migrate from surrounding tissues including the myocardium into the SIS-ECM matrix, and ex-vivo culturing of explanted SIS-ECM identified that the interaction between the fibroblasts and SIS-ECM creates a new bioactive construct releasing proangiogenic and proinflammatory proteins, creating a rich milieu conducive to the recruitment of proangiogenic immune cells. Mechanistic testing identified nuclear remnants in the SIS-ECM matrix that has been shown to modulate fibroblasts through toll-like receptor-9 signaling pathways to promote proangiogenic and proinflammatory activity. Finally, resonant confocal microscopy demonstrates regional neovascularization in close proximity to the SIS-ECM material, a likely consequence of the aforementioned paracrine and immune changes. Ultimately, this study identifies a key immune pathway leveraged by SIS-ECM biomaterials and demonstrates its proangiogenic immunomodulatory capacity. In a subsequent study, we further investigated the immunomodulatory properties of SIS-ECM by targeting the pericardial space. The pericardium has recently been shown to contain pro-reparative immune cell populations and, given the low molecular turnover in this space, the introduction of a bioactive material may influence pericardial and myocardial immune responses to optimize cardiac healing after myocardial infarction. In a small animal model of myocardial infarction, we delivered a micronized (powder) SIS-ECM to the pericardial space. After 28 days, pressure-volume loops demonstrated improved markers of diastolic and systolic cardiac function. Resonant confocal microscopy of the myocardial border zone also demonstrated an increased normalized fluorescent signal for small blood vessel density, suggestive of myocardial angiogenesis. Multiplex protein quantification of the border zone myocardium identified upregulation of proangiogenic vascular endothelial growth factor (VEGF), eosinophil chemoattractant eotaxin, and pro-reparative interleukin-4 (IL-4). As VEGF and IL-4 can be produced by eosinophils, flow cytometry was performed to characterize and quantify immune cell populations in the myocardium, demonstrating an increase in eosinophils in the biomaterial group. After identifying that eosinophils are upregulated, cardiac function and resonant confocal angiogenesis staining were performed in an eosinophil knockout mouse. Genetic depletion negated biomaterial-mediated benefits to cardiac function and angiogenesis, demonstrating for the first time that the eosinophil plays a critical role in biomaterial-mediated cardiac repair. These studies demonstrate the immunomodulatory properties of SIS-ECM biomaterials, and show an early therapeutic signal suggestive of angiogenesis and improved cardiac function. Large animal studies will be required to further evaluate the efficacy and immunomodulatory properties of SIS-ECM, and will also be required for the development of a safe pericardial delivery strategy for micronized SIS-ECM
Can Mesenchymal Stem Cells Inhibit the Formation of Saccular Aneurysms?
No full textIntracranial saccular aneurysms are pathological dilations of cerebral blood vessels that can spontaneously rupture leading to significant morbidity and mortality. Our current understanding of saccular aneurysm pathogenesis involves a complex interplay of predisposing factors and inflammatory cascades, leading to an outpouching at the site of a vessel bifurcation. While several treatments exist today, none are aimed at preventing aneurysm formation. Mesenchymal stem cells are pluripotent cells that have interesting immunomodulatory properties and have been studied in the context of many inflammatory diseases. Few studies have addressed aneurysms and suggest that these cells have the potential to be adjuvants to current treatment modalities in treating fully formed aneurysms. This thesis details the first studies investigating the use of mesenchymal stem cells in preventing the formation of saccular aneurysms. A pre- clinical trial was conducted, as well as an in vivo localization experiment to determine the potential mechanism of action
An Experimental Approach to Explore Abdominal Aortic Aneurysms in Rabbit Model
No full textThe diagnosis of an Abdominal Aortic Aneurysm (AAA) is currently made based on maximum diameter, which fails to accurately predict risks of rupture. The purpose of this study was to advance our understanding of AAA evolution using a rabbit model. AAAs were developed in rabbits using a periaortic incubation of CaCl2 and elastase. Rabbits were imaged using 3D angiography at 0 (healthy), 2, 4, and 6 weeks. Material properties and histological analyses were obtained for each stage. Results showed an increase in maximum diameter and wall thickness with aneurysmal tissue. The healthy aorta was stronger than all aneurysmal tissue. Tissue at 6 weeks had the stiffest and strongest properties compared to aneurysmal tissue. Elastin degradation and separation between wall layers was observed in all aneurysmal tissue with the highest collagen remodeling at 6 weeks. Because human aneurysms are diagnosed at an unknown time after initial formation, control animal experiments are necessary to understand the evolution of the mechanical and histological properties of the aortic tissue
- …
