Gold and Iron Loaded Micelles: A Multifunctional Approach for Combined Imaging and Therapy, With Improved Pharmacokinetics

Radiation therapy is an important component in the treatment and management of cancer patients. Despite current advances in imaging technologies and treatment planning strategies, a major limitation persists in accurately delineating tumor from normal tissue resulting in radiation–induced damage to healthy structures. Therefore, the frequency and dose of radiation exposure is limited by the generated toxicity in healthy tissues. The use of nanoparticles for contrast–enhanced imaging could improve the accuracy of therapeutic delivery and guide radiation treatments to maximize delivery to disease target tissues while sparing adjacent normal structures. Further, advancements in radiation therapy focus on the use of radiosensitizers that are intended to enhance tumor cell killing while minimizing effects on normal tissue. We have developed multifunctional nanoplatforms, containing sub–nanometer gold and iron nanoparticles that can provide contrast enhancement using computed tomography and magnetic resonance imaging, while also serving as radiosensitizers for X–ray therapy. The effectiveness of these nanoparticles was evaluated in vivo demonstrating an improvement in both tumor margin visualization for image-guided radiation therapy and overall survival in tumor bearing mice. Importantly, we found that measurements of contrast enhancement in imaging correlated strongly with tumor response after radiation therapy. Furthermore, we have found that by encapsulating sub–nanometer gold particles within micelles we are able achieve improved excretion profiles compared to larger gold particles, with gold detected in both urine and feces suggesting that particles within this size range are more efficiently removed by the kidneys and liver. Finally, the use of an actively targeted nanoplatform can achieve higher tumor retention, facilitate nanoparticle internalization, and improve tumor specificity. To facilitate the introduction of targeting molecules onto micelle formulations, a naturally occurring surfactant protein oleosin was used to stabilize superparamagnetic iron oxide clusters. Functionalization with targeting ligands (e.g. Her2/neu affibody) was achieved by fusing the biologically relevant motifs to oleosin using standard cloning techniques, and cell specific targeting was confirmed using magnetic relaxation techniques. In the future, we envision that strategies like this will minimize the off–target effects of radiation, reduce tumor burden, provide information on the likelihood of tumor regression in response to therapy and reduce long–term nanoparticle retention

Service oriented computing for dynamic virtual learning environments

Using the Internet for teaching and learning has become a trend in modern higher education, facilitated through the exploitation of advanced computing technologies. Virtual Learning Environment (VLE) applications support online learning over the Internet, and VLEs have thus emerged as e-learning domains that are essential prerequisites in cutting edge design and implementation technologies in education. Service Oriented Computing (SOC), as a novel software development and implementation approach, has become an active area of research and development. Web services, as an example of SOC, support the integration of software applications in an incremental way, using existing platforms and languages that utilize and adopt existing legacy systems. Thus, VLEs should be particularly well suited to Web ser- vices through the SOC approach. VLE services is a field subjected to continuous development but VLEs as Web services are still not generally accessible for academic institutions, although they have been adopted by some scientific projects. The next generation of VLEs should address the limitations of the current online systems by providing a richer context for online learning, one that is sensitive to the specific domain requirements of e-learning. Web Services Matching and Selection (WSMS), as a part of the functional requirements of Web services, has received less attention from SOC researchers. It involves discovering a set of semantically equivalent services by filtering a set of available services based on service metadata, and instantaneously selecting the best possible service. WSMS is the discovery of a service by a user, where correspondence is established between the objectives of the consumer and the capabilities of the service. It thereby aims to match and select the optimal service that best meets the requestor's needs. The main aim of this doctoral work is to explore novel architectural designs for VLEs, based on the SOC paradigm and its related techniques. In addition, this investigation aims to extend the core ideas behind VLE tools, which are gradually becoming dominant within academic institutes. Another aim is to devise a policy- based technique to enforce security requirements for VLEs and to build a test-bed for VLE security based on Modular Moodle. The fundamental contribution of this thesis that it demonstrates that VLEs can be considered as services, which can be published, discovered and composed as perceived in the SOC paradigm. An additional contribution to the knowledge is that it has built a new extension to the structure of Web services: the Web Services Matching and Selection (WSMS) system. Another contribution to the knowledge is that traditional security requirements have been modified to cater for the highly mobile and changeable environment of VLEs; this has been achieved through policy- based techniques. These contributions to the body of knowledge have been published in learned journals and at conferences

Management of Hepatitis C Virus Infection in Patients with Cirrhosis

In this chapter, we review the history of HCV infection in patients with liver cirrhosis. Selection of appropriate regimens for HCV-infected patients with cirrhosis, consistent with approved indications, practice guidelines, and emerging data is presented. Finally, this chapter explains individualization of therapy to maximize SVR rates in HCV-infected patients with cirrhosis and to critically appraise the role of newer agents and regimens in the management of HCV-infected patients with cirrhosis

MRI visualization of optic nerve avulsion due to ocular perforation from BB gun projectile

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.To report a case of optic nerve avulsion after a perforating injury by an air-soft/BB gun that was successfully captured with magnetic resonance imaging

Vitamin D deficiency prevalence and predictors in early pregnancy among Arab women

Data regarding the prevalence and predictors of vitamin D deficiency during early pregnancy are limited. This study aims to fill this gap. A total of 578 Saudi women in their 1st trimester of pregnancy were recruited between January 2014 and December 2015 from three tertiary care antenatal clinics in Riyadh, Saudi Arabia. Information collected includes socio-economic, anthropometric, and biochemical data, including serum vitamin D (25(OH)D) levels, intake of calcium and vitamin D, physical activity, and sun exposure indices. Pregnant women with 25(OH)D levels 3.5), low HDL-cholesterol, and living in West Riyadh were significant independent predictors for vitamin D deficiency, with odds ratios (ORs) (95% confidence interval) of 25.4 (5.5–117.3), 17.8 (2.3–138.5), 4.0 (1.7–9.5), 3.3 (1.4–7.9), 2.8 (1.2–6.4), and 2.0 (1.1–3.5), respectively. Factors like increased physical activity, sun exposure at noon, sunrise or sunset, high educational status, and residence in North Riyadh were protective against vitamin D deficiency with ORs 0.2 (0.1–0.5); 0.2 (0.1–0.6); 0.3 (0.1–0.9); and 0.4 (0.2–0.8), respectively. All ORs were adjusted for age, BMI, sun exposure, parity, summer season, vitamin D intake, multivitamin intake, physical activity, education, employment, living in the north, and coverage with clothing. In conclusion, the prevalence of vitamin D deficiency among Saudi women during early pregnancy was high (81%). Timely detection and appropriate supplementation with adequate amounts of vitamin D should reduce the risks of vitamin D deficiency and its complications during pregnancy

Pharmacotherapy of Hepatic Encephalopathy

Hepatic encephalopathy (HE) or portosystemic encephalopathy (PSE) is a serious neuropsychiatric disorder resulting from liver failure. It is one of the common complications of liver cirrhosis and portosystemic shunting (PSS). Ammonia accumulation is one of the well-established causes. Ammonia is a by-product of the intestinal bacteria as a result of the breakdown of dietary supplements. In the normal state of the liver, the peripheral hepatocyte contains glutaminase that converts glutamine into glutamate and ammonia; ammonia will be detoxified and converted into urea. The variant manifestations were linked to the severity of HE. A wide range of neurological and psychiatric signs have been reported. The International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) uses asterixis (i.e., flapping tremor) as the first clinical sign of HE. Four factors should be taken into consideration to classify and distinguish HE from other conditions: HE type, severity of manifestations following West-Haven Criteria (WHC), HE time course, and presence of precipitating factors. Nonabsorbable disaccharides (lactulose and lactitol) and rifaximin have been the standard of care as first- and second-line therapies, respectively. Non-pharmacological interventions had a crucial role in HE management. Liver transplantation is the ultimate management of hepatic cirrhosis

Ocular infarction following ethanol sclerotherapy of an arteriovenous malformation

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Purpose: To illustrate a case of ocular infarction following percutaneous ethanol sclerotherapy of an orbital arteriovenous malformation. Observations: The patient is a 31-year-old female who developed ocular infarction of the left eye with light perception vision, proptosis, ophthalmoplegia, and a cherry red spot following sclerotherapy of an orbital arteriovenous malformation. Fluorescein angiography demonstrated decreased arteriolar filling with vascular leakage, indocyanine green angiography showed decreased choroidal perfusion, and optical coherence tomography revealed full thickness retinal edema. Magnetic resonance angiography and venography were negative for venous sinus thrombosis or intracranial vascular compromise. Conclusions and Importance: Ocular infarction is a rare and devastating disorder that may result in permanent vision loss. Ethanol sclerotherapy has been reported to be effective in treating arteriovenous malformations. To the best of our knowledge, this is the first report in the literature of ocular infarction following percutaneous ethanol sclerotherapy to highlight this disease with multimodal imagin

Stem Cells and Liver Disease

Liver transplantation is the primary treatment for various end-stage hepaticdiseases but is hindered by the lack of donor organs, complications associated with rejection and immunosuppression. An increasingly unbridgeable gap exists between the supply and demand of transplantable organs. Hence stem cell research and regenerative medicine have the potential to revolutionize the future of medicine with the ability toregenerate damaged and diseased organs. Stem cells serving as a repair system for the body, can theoretically divide without limit to replenish other cells. These cells could relieve the symptoms of liver disease or the genetic error could potentially be corrected by gene therapy. In cases of acute liver failure in adults, stem cell therapies might be used to support the liver, allowing it time to recover