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No description available.

The lymphatic system comprises a network of vessels whose primary functions are the maintenance of extracellular fluid balance and the transport of antigen-presenting cells from the periphery to the lymph nodes, thus facilitating immunological surveillance of the tissues and activation of adaptive immunity. In malignant disease, the lymphatics are both a route for dissemination and a reservoir for metastatic cancers such as cutaneous melanoma and breast carcinoma, where lymph node involvement is an early indicator of prognosis. Yet, despite such obvious importance in disease, the fundamental biology of the lymphatics is poorly understood and critical mechanisms such as those underlying trafficking of dendritic and tumour cells have been largely overlooked. The focus of this thesis is lymphatic vessel endothelial hyaluronan receptor LYVE-1, and the regulation of its binding to the extracellular matrix glycosaminoglycan, hyaluronan (HA). Found selectively on the surface of lymphatic vessels, but sharing many of the features of the leukocyte homing receptor CD44, LYVE-1 appears a likely candidate for regulation of lymphatic trafficking during the stage at which cells migrate into the vessel. However, the precise function of LYVE-1 in recent years has remained enigmatic, not least because the native receptor is subject to post-translational modification with sialic acid, with the effect that HA binding is inhibited in lymphatic endothelium. The results of this thesis demonstrate that sialylation of LYVE-1 is not a short term regulatory modification, but rather a longer term mechanism that imposes a requirement for higher order receptor complex formation or HA crosslinking to achieve stable binding. This implies that native LYVE-1 is an active HA binding protein even when sialylated, with implications for our understanding of the role played by the receptor in HA uptake and metabolism, and transmigration of lymphatic endothelium by migratory leukocytes. Like CD44, HA binding to LYVE-1 is dependent on multivalent interactions between receptor and ligand, and may be enhanced by processes that increase the avidity of the interaction. Here for the first time it is shown that the native LYVE-1 molecule on lymphatic endothelium may be activated to bind HA following clustering of the receptor, or presentation of HA in a cross-linked form, such as that resulting from incubation with the HA binding protein TSG-6.

Adult adipose derived mesenchymal stromal cells (ASCs) have been characterized in various species. Many factors may affect ASC fate and ASCs from different species may have different response to these factors. The first study was to identify the differences of the canine ASCs isolated from subcutaneous and infrapatellar adipose tissues, and evaluate the impact of cryopreservation on the cells. Based on paired comparisons of fresh and cryopreserved ASCs, cryopreserved ASCs had lower CD29 and CD44 protein expression and lower proliferation rates. The cryopreserved ASCs had relative lower mitochondria in the cytoplasm compared to the fresh ASCs regardless of tissue sources. The second study was to apply human ASCs for bone regeneration. The spinner flask bioreactor system was employed to load human ASCs onto three commercial scaffolds and the cell-scaffold constructs were cultured in stromal, osteogenic, or osteogenic for 48 hours followed by stromal medium for up to 28 days. The distinct scaffold upregulated different osteogenic signaling pathways, suggesting distinct osteogenic cell signaling pathways were selectively upregulated by scaffold composition. The third study was designed to quantify in vivo equine multipotent stromal cell (MSC) osteogenesis on synthetic polymer scaffolds with distinct mineral combinations 9 weeks after implantation in a murine model. Addition of mineral to polymer scaffolds enhanced equine MSC osteogenesis over polymer alone, and contributions by both exo- and endogenous MSCs were confirmed. The fourth study was designed to evaluate the effects of collagenase digestion and cryopreservation on equine ASCs. Higher collagenase concentration yielded more nucleated cells, and the percentages of MHCII-, CD44+, CD105+ cells in freshly isolated and cryopreserved cells were similar. The embryonic gene expression was enhanced and the essential gene expression decreased after cryopreservation. The fifth study was to demonstrate the endodermal transdifferentiation capability in feline ASCs. xvi Feline-specific pancreatic β cell induction medium was developed in the study, and islet-like cell clusters that secrete insulin in response to glucose stimulation were created. Overall, the investigations in this dissertation provide critical information for canine, feline, equine and human MSC-based tissue engineering therapies and may contribute to better efficiency and efficacy of cell

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No description available.

Clinical trials are generally considered the foremost authority for generating robust medical evidence because of their methodological strengths relative to other clinical research designs. However, they are susceptible to substantial challenges, such as enrollment barriers, low participation rates, high operational costs, and limited results generalizability, to name a few. A promising resource to address these challenges is real-world data (RWD), generally defined as routinely collected data during the delivery of healthcare. Database-specific RWD – such as electronic health records (EHRs), administrative claims, and clinical registries – is of particular interest for their richness and volume. However, coordination between the primary data collection actions of clinical trials with the secondary collection nature of RWD, while also accounting for data fitness-for-use considerations, persists as a prominent challenge. This dissertation aims to advance the sciences of using RWD to enhance clinical trials, specifically from two perspectives: (1) a trial design perspective; and (2) a results interpretation perspective. It first reviews relevant literature about RWD uses for clinical trial conduct. It then seeks to address two research questions focused on using RWD to improve clinical trials, with particular emphasis on clinical trials that evaluate medications: (1) how do eligibility criteria, both individually and in combination, affect patient safety and recruitment pool size; and (2) how representative of real-world patients are enrolled trial participants. The utility of RWD in investigating these questions is tested using two aims. Aim 1 examines the impact on hospitalization risk and eligible patient pool size of different eligibility criteria combinations across a variety of disease domains. Aim 2 clinically characterizes trial participants for generalizability assessments. The primary innovations of this dissertation include (1) supplementing a RWD source with trial enrollment data, thus creating a novel combination for enriched evaluations; and (2) developing innovative approaches, both across sets of clinical trials and within individual trials, for generalizability assessments. Ultimately, the findings of this dissertation demonstrate how clinical trial design, and the interpretation of their results, can be enhanced through the use of RWD in order to strengthen clinical research pursuits in study design and results interpretation.

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Injurious falls often have tragic consequences such as loss of independence, bodily harm and high monetary costs. Evidence on the effects of lexical cognitive tasks on gait in healthy older individuals is lacking. This study investigated the effects of a specific language task on changes in gait that might put people at risk for injurious falls. Participants included 6 males and 6 females, aged 59 to 77. The GAITRite Walkway System was used to generate a Functional Ambulatory Profile (FAP) score for each trial. FAP is derived from a formula that includes critical gait parameters highly related to risk of falls. The higher the lower the FAP score, the more likely the individual will experience an injurious fall. Scores range from 0 to 100, however, 95 to 100 is considered within normal limits. The three walking conditions included the following: walking without talking (baseline), walking while saying the months of the year forward (low-load) and walking while saying the months of the year backward (high-load). Cognitive-linguistic load was manipulated while phonological, lexical and semantic characteristics remained the same throughout each condition. Results showed the following: differences in velocity and double support time variables were statistically significant among all conditions. Older individuals demonstrated a statistically significant lowered FAP and stride length score across conditions of walking alone and simultaneous walking and reciting the months of the year backwards. Results revealed that differences in velocity and double support time variables were statistically significant across all conditions. Moreover, velocity and double support time may be assumed to significantly influence fall risk across all conditions. Our sample of older individuals demonstrated a statistically significant lowered FAP and stride length score across conditions of walking alone and simultaneous walking and reciting the months of the year backwards (higher cognitive load). However conditions of walking alone and simultaneous walking and reciting the months of the year forwards and conditions of reciting the months of the year forwards compared to reciting the months of the year backwards were non statistically significant. More research must be conducted to identify specific lexical cognitive tasks that most affect gait within different populations and disorders. The ultimate goal is to educate individuals who are at risk for injurious falls on the specific language tasks to avoid while ambulating. This data may prevent or minimize the frequency in which persons simultaneously walk and talk, hopefully to decrease prevalence of injurious falls. / A Thesis submitted to the School of Communication Science and Disorders in partial fulfillment of the requirements for the degree of Master of Science. / Summer Semester 2015. / June 12, 2015. / Automatics, Cognitive Load, Falls, Functional Ambulation Profile, Gait, Older / Includes bibliographical references. / Leonard L. LaPointe, Professor Directing Thesis; Julie A. G. Stierwalt, Committee Member; Michael P. Kaschak, Committee Member.

Kheirabadi Z. Patienternas upplevelser av livsstilsförändring vid typ 2 diabetes.En litteraturstudie. Examensarbete i omvårdnad (OM153B), 15 högskolepoäng.Malmöuniversitet: Fakulteten för Hälsa och Samhälle, Institutionen förvårdvetenskap, Vårtermin 2022.Bakgrund: Antalet individer som lider av typ 2 diabetes ökar varje år. Typ 2diabetes är en av de vanligaste långvariga sjukdomarna. Typ 2 diabetes kan ävenräknas som en livsstilsrelaterad sjukdom som grundar sig på ohälsosammalevnadsvanor som ökar sjukdomsrisken genom exempelvis olämplig kost, brist påfysisk aktivitet, samt tobak och alkoholkonsumtion. En av de behandlingar somkan hjälpa patienter att främja hälsan utan medicinering samt livskvalitetsutveckling är därmed livsstilsförändring.Syfte: Studien ämnar belysa patienters upplevelser av livsstilsförändring vid typ2 diabetes.Metod: Studien använder 14 vetenskapliga artiklar med kvalitativ metod.Utvalda artiklar hämtades från både CINAHL och PubMed databaser sominriktar sig på medicin och omvårdnad. Kvalitativgranskning av artiklarnagenomfördes enligt Statens beredning för medicinsk och social utvärdering(SBU:s mall) 2014.Resultat: Detta utgår ifrån 14 artiklar med kvalitativ ansats från åtta länder.Resultatet presenteras i fyra teman: 1) Motivationens roll hos patienter attgenomföra livsstilsförändring 2) Rollen av stöd och undervisning för patienter vidlivsstilsförändring 3) Patienternas upplevelser av förändringar 4) Effekter avlivsstilsförändring på individens livskvalitet. Motivation är första och främstaanledningen som kan påverka individers livsstilsförändring positivt eller negativt.Undervisning och stöd från anhöriga och hälsosjukvårdpersonal har också enviktig roll för livsstilsförändringar. Varje individ upplever livsstilsförändringar påolika sätt som utgår från individens känslor och livserfarenheter.Konklusion: Studien visar att en insikt om diabetes behövs hos individer för attdessa ska lyckas förändra sina ohälsosamma levnadsvanor till en förbättring av sinlivsstil och ökad livskvalitet.Nyckelord: diabetespatienter, typ 2 diabetes, livsstilsförändringar, patientensupplevelse, kvalitativ.