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

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

Quarrels between Young Refugees and Young Germans in Bautzen: How Has it Turned into Bad Treatment against Refugees and What Are the Effects?

In recent years, more than a million asylum seekers have entered Germany, and it tries actively to integrate them into society. However, this massive process faces some difficulties especially in the east of the country. This article explores how the conflicts between young refugees and young Germans, mobilized, and turned to bad treatment, from some people in the city, against not only young refugees, but also against other refugees in the city, by studying kind of the communication between the host society and the refugees in two main areas: public places and the private sector. Comparing the results with the prior interviews conducted with fifteen unaccompanied minors and adult refugees in Hamm city, this article shows how the conflict that turned into bad treatment has negatively affected the feeling of security for the refugees, the homogeneity of the refugee community, and their views for their future in Germany regardless of the huge efforts of the government and the civil society to integrate the refugees in Bautzen city

Las economías sirias: ¿un boom temporal?

Algunas personas desplazadas y sus comunidades de acogida se han beneficiado económicamente de las consecuencias del conflicto en la provincia siria de Al Raqa. Otras necesitan ayuda de un tipo que irá variando a medida que cambien las circunstancias

Pharmacological Therapy of Ascites

Ascites refer to accumulation of fluids in the peritoneal cavity. Ascites is caused by multiple causes, among which liver cirrhosis is the commonest. Confirming the etiology is the first and most important step toward proper management. Assuming that ascites is always caused by cirrhosis can lead to unnecessarily sending patients with different etiologies for liver transplantation, particularly patients with non-cirrhotic portal hypertension. Calculating serum albumin ascitic gradient is important in differentiating ascites due to portal hypertension from other etiologies. The first-line therapy for ascites in cirrhosis is low salt diet and diuretics. It is important to avoid nonsteroidal anti-inflammatory drugs (NSAIDs) and nephrotoxic medications in these patients

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

The Association Between FokI Vitamin D Receptor Polymorphisms With Metabolic Syndrome Among Pregnant Arab Women

Metabolic syndrome (MetS) is a serious health condition that is becoming extremely threatening in Saudi Arabia. The link between vitamin D receptor (VDR) gene polymorphisms and maternal MetS has been observed in several ethnic groups, but is yet to be clarified in the Arabian population. This study aims to investigate the relationship between the FokI VDR genotype and the risk of MetS and its components in pregnant Saudi women. A cross-sectional study was conducted using 368 pregnant Saudi women on first trimester screened for MetS (44 with MetS and 324 without MetS). Measurements included anthropometrics, glycemic and lipid profile and 25(OH)D. TaqMan genotyping assay was used to determine Fokl VDR genotype of participants. Vitamin D deficiency (25(OH)D <50nmol/l) was seen in 85% of the participants. An estimated 12% of participants had MetS. In the MetS group, the FokI VDR genotyping frequencies for FF, Ff, and ff genotypes were 50%, 36.4% and 13.6%, respectively. In controls, the frequencies were 62.7%, 31.4% and 5.9%, respectively. No significant association between the individual MetS components and FokI VDR genotypes were observed. Nevertheless, carriers of the ff allele had a significant risk for full maternal MetS [Odds Ratio 4.2 (95% Confidence Interval 1.4-12.2; adjusted p=0.009). The study suggests that the ff FokI VDR genotype is a genetic marker of maternal MetS in pregnant Arabian women. Prospective studies that include neonatal outcomes may confirm present findings

Obesity, diabetes and longevity in the Gulf: is there a Gulf Metabolic Syndrome?

The Gulf is experiencing a pandemic of lifestyle-induced obesity and type 2 diabetes mellitus (T2DM), with rates exceeding 50 and 30%, respectively. It is likely that T2DM represents the tip of a very large metabolic syndrome iceberg, which precedes T2DM by many years and is associated with abnormal/ectopic fat distribution, pathological systemic oxidative stress and inflammation. However, the definitions are still evolving with the role of different fat depots being critical. Hormetic stimuli, which include exercise, calorie restriction, temperature extremes, dehydration and even some dietary components (such as plant polyphenols), may well modulate fat deposition. All induce physiological levels of oxidative stress, which results in mitochondrial biogenesis and increased anti-oxidant capacity, improving metabolic flexibility and the ability to deal with lipids. We propose that the Gulf Metabolic Syndrome results from an unusually rapid loss of hormetic stimuli within an epigenetically important time frame of 2-3 generations. Epigenetics indicates that thriftiness can be programmed by the environment and passed down through several generations. Thus this loss of hormesis can result in continuation of metabolic inflexibility, with mothers exposing the foetus to a milieu that perpetuates a stressed epigenotype. As the metabolic syndrome increases oxidative stress and reduces life expectancy, a better descriptor may therefore be the Lifestyle-Induced Metabolic Inflexibility and accelerated AGEing syndrome – LIMIT-AGE. As life expectancy in the Gulf begins to fall, with perhaps a third of this life being unhealthy – including premature loss of sexual function, it is vital to detect evidence of this condition as early in life as possible. One effective way to do this is by detecting evidence of metabolic inflexibility by studying body fat content and distribution by magnetic resonance (MR). The Gulf Metabolic Syndrome thus represents an accelerated form of the metabolic syndrome induced by the unprecedented rapidity of lifestyle change in the region, the stress of which is being passed from generation to generation and may be accumulative. The fundamental cause is probably due to a rapid increase in countrywide wealth. This has benefited most socioeconomic groups, resulting in the development of an obesogenic environment as the result of the rapid adoption of Western labour saving and stress relieving devices (e.g. cars and air conditioning), as well as the associated high calorie diet