Malaria accounts for 198 million cases worldwide; with a high mortality rate. 584000 deaths were reported in 2013. Malaria is a re-emerging disease globally due to drug resistance, parasite recrudescence and non-availability of a vaccine. Chloroquine, quinine and antifolates served as frontline antimalarial drugs for decades. Development of resistance to chloroquine and antifolates, and the decreased efficacy of mefloquine, and even quinine, in malaria-endemic regions, has led to artemisinin derivatives evolving as frontline drugs. Artemisinin is a potent antimalarial compound and clears around 104 parasites per cycle. Despite being a potent antimalarial, artemisinin derivatives suffer from poor pharmacokinetic properties and short half lives. This has led to the development of artemisinin-based combination therapies (ACTs) using a partner drug with a longer half-life. However, resistance to ACTs has been reported in the last few years, perhaps due to lack of adherence to prescribed regimens or suboptimal treatment and the use of counterfeit drugs. Therefore there is an urgent need to develop an alternative ACT which overcomes these limitations. This thesis entitled “Adjunct therapy with curcumin for the treatment of malaria: studies in a murine model” describes the antimalarial activity of curcumin and artemisinin and the adjunct role of curcumin in the prevention of parasite recrudescence and cerebral malaria. The thesis is divided into three chapters: The first chapter entitled “Introduction: Malaria and anti-malarial drugs” consists of a brief introduction of malaria, the parasite life cycle and currently known antimalarial drugs. During the course of infection, the Plasmodium undergoes sporogony in the mosquito, and merogony and schizogony in the human host. All these life cycle stages are briefly described with depictions. A major part of this chapter is dedicated to describe antimalarial compounds under the following headings 1. Quinoline derivatives 2. 4-aminoquinolines 3. Antifolates 4. Artemisinin derivatives 5. Antibiotics and 6. Curcumin. The second chapter is aimed at examining the ability of curcumin-arteether (a synthetic derivative of artemisinin) combination therapy in preventing parasite recrudescence in a murine model through immunomodulation employing various immunological, molecular biological, and biochemical techniques. The use of suboptimal doses of antimalarial drugs leads to recrudescence or relapse of malaria (reappearance of the parasite in blood after antimalarial regimen). In the present study we have addressed this issue by the use of curcumin as an adjunct molecule with α,β arteether (a synthetic derivative of artemisinin). We have studied recrudescence in a Swiss mice model. A suboptimal dose was standardized by the use of different doses of α,β arteether (AE) ranging from 250µg to 1500 µg. We found 750 µg to be a suboptimal dose and studied the adjunct nature of curcumin when animals were treated with AE suboptimal dose or AE+curcumin (AC) combination treatment and monitored the survival of animals. Our results clearly demonstrate that ~95% of animals treated with the suboptimal AE dose died of recrudescent malaria but there was almost 100% survival of AC-treated animals; these animals were under observation for at least 3 months. We have studied the effect of curcumin in a recrudescence model at the molecular level. Curcumin by itself has antimalarial activity, but only in combination with α,β arteether prevented recrudescence. Our results indicate that curcumin has immunomodulatory activity. Serum cytokine analysis and spleen mRNA analysis for proinflammatory and anti-inflammatory mediators indicate that AC treatment effectively reduced both mRNA and serum cytokine levels of IFNγ, TNFα, IL-12 and effectively increased both mRNA and serum levels IL-10 and antibodies of the IgG subclass. Using TLR2 and IL-10 knockout animals, we have conclusively demonstrated that TLR2 is involved in the production of IL-10, and IL-10 is required for the AC-mediated protection of animals during the recrudescence period. We conclude that curcumin is able to prevent parasite recrudescence essentially by switching the Th1 response to a Th2 response. The third chapter deals with the study the effect of areether-curcumin (AC) combination therapy in the prevention of Experimental Cerebral Malaria. Although malaria mortality rates have decreased by an impressive 47% between 2000 and 2013, it is still a major affliction of mankind (WHO 2014). Plasmodium falciparum infection causes human cerebral malaria (HCM). The mortality rate in HCM is unacceptably high (15–20%), despite the availability of artemisinin-based therapy. HCM is characterized by a rapid progression from headache, general malaise, and prostration to hemiparesis, ataxia, unrousable coma, and death. Paediatric HCM deaths are mostly due to respiratory arrest. Alternatively, death may be due to parasite-mediated injury to a sensitive location; a small lesion due to parasite in brain stem can cause sudden respiratory arrest. In HCM, cytoadherence of pRBCs in brain microvasculature has been implicated as a major contributing factor for CM pathology. The failure of a large number of adjunct therapies in HCM demands the development of new intervention strategies. An effective adjunct therapy is urgently needed. Experimental Cerebral Malaria (ECM) in mice manifests many of the neurological features of HCM. In this study, we have demonstrated the efficacy of curcumin and PLGA nanocurcumin in the treatment of Experimental Cerebral Malaria (ECM), using the Plasmodium berghei ANKA-infected mouse model (C57BL/6). Curcumin/PLGA nanocurcumin alone can prevent the onset of ECM. We have shown that curcumin/PLGA nanocurcumin can prevent CD8+ T cell, CXCR3+ CD8 T cell and parasite-infected RBC (pRBC) sequestration in the brain. These are also the essential parameters underlying HCM. We have also demonstrated that curcumin effectively inhibits T cell proliferation in spleen. We have explained the anti-inflammatory effects of curcumin by showing the inhibition of NF-B in both brain and spleen, which is a plausible explanation. But, curcumin/PLGA nanocurcumin treated animals died later due to build up of parasitemia in blood and subsequent anemia. Moreover, a combination therapy with arteether and curcumin given even after the onset of neurological symptoms can completely cure and protect the animals against mortality. We have tested AC-combination after the onset of symptoms to mimic patient conditions in HCM, since the murine regimens reported were not successful in the treatment of HCM. Our results clearly demonstrate that AC treatment even after the onset of symptoms ensures 100% survival. Since the bioavailability of curcumin is reported to be poor, we have also tested the efficacy of PLGA nanocurcumin and find that it is superior to native curcumin in terms of therapeutic effects. It is concluded that curcumin would be an ideal adjunct drug to be used with the artemisinin derivatives to treat malaria, including cerebral malaria.

L’engagement du Conseil de l’Europe en faveur d’une éducation plurilingue intégrant altérité et diversité culturelle est fortement lié au souci de promouvoir la communication entre citoyens de langue et culture différentes, indispensable à la mobilité et à la compréhension réciproque. Dans ce nouveau référentiel s’inscrit la tendance à enseigner les disciplines non linguistiques, directement dans la L2. Cette méthode d’enseignement d’une matière par intégration d’une langue étrangère, appelée EMILE a vocation d’accélérer le processus d’apprentissage. Or, il s’est avéré, lors d’une recherche-action portant sur l’anglais juridique, qu’une méthode d’immersion complète telle qu’EMILE pouvait présenter certaines failles pour apprendre cette langue de spécialité très pointue. Pour combler ces failles, nous proposons la méthode LADMI (Linguistique appliquée à une autre discipline par méthode intégrative), qui est une modification du concept d’EMILE extrapolant à partir d’une certaine structure logique, suite à des observations particulières, afin de préserver à la fois la langue et le contenu de la DNL, le droit. / The European Council’s policy of promoting linguistic and cultural diversity in the field of acquisition-teaching of foreign languages, has led to a profoundly modified situation in language learning. With the aim of encouraging mobility among students and teachers in the European education system, pluralinguistic methods, such as TIE-CLIL (Translanguage in Europe – Content and Language Integrated Learning) are used in an attempt to accelerate immersion programmes. However, in an action research undertaken in Legal English at the University of Nice, the conclusion was drawn that language immersion is not always feasible in Law. Therefore an integrated approach, Adjunct CLIL, based on logical observations, a modification of the concept CLIL : ALDIM (Applied Linguistics to another Discipline by Integrated Method), is suggested, to preserve both the quality of the language as well as content of the non-linguistic discipline, Law.

Postoperative pain is of serious concern to patients and anesthesia providers alike. Management of a patients’ pain is a central component of anesthesia care. Ketamine as an anesthetic agent has been available for 50 years. It has been utilized as a general anesthetic and selectively as an anesthetic agent for high-risk patients. Due to dysphoric side effects associated with the dosage required to render general anesthesia, anesthesia providers may be reluctant to utilize this medication to its full potential. Recently there has been a resurgence of interest in ketamine as an analgesic agent. The researcher for this project performed a thorough literature review focusing on intravenous ketamine as an adjunct to standard opioid-based analgesia for postoperative pain. Four systematic reviews published in the last 10 years support the safety and efficacy of ketamine when administered intravenously in sub-anesthetic doses. The purpose of this project was to provide evidence-based education to anesthesia providers regarding the benefits of ketamine and follow-up to evaluate for evidence of changes in practice after the educational At a large community hospital data concerning ketamine utilization by anesthesia providers as a component of multimodal analgesia was collected for a six-month period, including three months pre- and three months post-educational intervention. Despite various methods utilized to present evidence regarding the safety and efficacy of ketamine, the results of this study demonstrated no significant change in practice. Based upon the extensive published literature the evidence is compelling that the addition of a sub-anesthetic (0.5 mg/kg) dose of ketamine to the surgical patient’s operative pain management plan would improve comfort and decrease opioid-related side effects with minimal negative impact.

Identification of predictors of treatment response in patients with major depressive disorder (MDD) may facilitate improved disease management. Data were pooled from two 6-week, double-blind, placebo-controlled studies of extended-release quetiapine (quetiapine XR; 150 or 300 mg/day) as adjunct to ongoing antidepressant therapy. Effects of psychiatric history and baseline demographic and disease characteristics on efficacy outcomes (Week 6 Montgomery Åsberg Depression Rating Scale [MADRS] total score reduction) were evaluated in population subgroups (quetiapine XR both doses pooled, n = 616; placebo, n = 303). Baseline Clinical Global Impressions-Severity (CGI-S) score and previous depressive episodes on Week 6 MADRS total score change, and baseline MADRS individual item scores on Week 6 change in CGI-Improvement score, were also evaluated. No major differences between responders and non-responders to quetiapine XR were observed for patient characteristics or demographic and disease characteristics. No suggestion of a predictive association was found between baseline CGI-S score, number of depressive episodes, and baseline MADRS item scores and efficacy outcomes. These analyses showed no major differences between responders and non-responders, and no predictive association between the parameters assessed and efficacy outcomes for adjunct quetiapine XR in patients with MDD and an inadequate response to prior antidepressant therapy.

No description available.

Text in Afrikaans / Tradisioneel is aanvaar dat die indirekte voorwerp nie in Afrikaanse stelsinne kan optree sander die voorkoms van 'n direkte voorwerp in dieselfde sin nie. Hierdie ondersoek het aan die lig gebring dat sekere voorwerpe wat voorheen as "direkte voorwerpe" geklassifiseer is, eerder die eienskappe van indirekte Hulle word dus nou geklassifiseer as en die parameters van die indirekte ooreenkomstig uitgebrei. Aangesien daar geen formele merkers vir die uitkenning en onderskeiding van direkte en indirecte voorwerpe bestaan nie, is parameters vir die doel vasgestel. Skoon indireckte voorwerpe (op enkele uisonderings na) verskyn altyd direk na die SPIL-posisie in 'n stelsin toon 'n groot affiniteit vir voorsetsels (versa vir, aan), en kan in die koers van adjunk afgegradeer word, deur me 'n voorsetsel te verbind, en kan sodoende ook na' 'n adjunk verskyn. Direkte voorwerpe kan daarenteen nie met voorset-: sels verbind nie en kan buitendien na enige adjunk verskyn. / Language Education, Arts and Culture / M.A. (Afrikaans)

Adjunct faculty comprise a large percentage of part-time faculty for many colleges and universities today. Adjunct faculty are hired because they are experts in their content areas; however, this does not guarantee that they are skilled in effective classroom management. These instructors can become bewildered and frustrated because they lack the knowledge and skills that are needed to run an effective classroom. While educational organizations have adopted blended learning environments as an effective delivery method for their students, this method has not gained much traction as a way to deliver instruction to their own employees. Thus, there are opportunities to use blended learning as a strategy for professional development in the workplace. What is more common in the workplace is the application of knowledge management (KM). KM is used in organizations to identify, share, and validate knowledge in order to improve individual and organizational performance. Blended learning combined with KM strategies, can leverage face-to-face and online instruction delivery methods to give adjunct faculty real-time support as they learn to implement specific instructional methods and classroom management techniques into their face-to-face classrooms. The goal was to construct and validate a blended learning professional development course for adjunct faculty. Design and development research methods were used to conduct the study in four phases. In phase one, a course design framework that integrated the four modes of the SECI KM model (i.e., socialization, externalization, internalization, and combination) was developed. Included with the framework was a mapping of the learning outcomes, knowledge type, and activities associated with each SECI mode. In phase two, an expert panel reviewed the framework and mapping. The Delphi technique was used to capture panel members’ feedback. Revisions to the framework and mapping were made based on the results of the expert review. In phase three, the framework was used to develop the course within the Desire2Learn learning management system. In phase four, a formative evaluation of the course was conducted using focus groups with key stakeholders including faculty, staff, and administrators. The sequential nature of the phases in which the professional development course was designed and developed resulted in a refined instantiation of the course, which was received positively by key stakeholders; however, summative and confirmative evaluations would be needed to determine the effectiveness of the course delivery and content, as well as, whether the course is viable over time. The incorporation of the SECI principles for faculty professional development was also determined to be worthy of continued consideration. Future research focusing on the implementation of SECI principles to guide instructional design in various online and blended learning contexts is recommended.

No description available.

Text in Afrikaans / Tradisioneel is aanvaar dat die indirekte voorwerp nie in Afrikaanse stelsinne kan optree sander die voorkoms van 'n direkte voorwerp in dieselfde sin nie. Hierdie ondersoek het aan die lig gebring dat sekere voorwerpe wat voorheen as "direkte voorwerpe" geklassifiseer is, eerder die eienskappe van indirekte Hulle word dus nou geklassifiseer as en die parameters van die indirekte ooreenkomstig uitgebrei. Aangesien daar geen formele merkers vir die uitkenning en onderskeiding van direkte en indirecte voorwerpe bestaan nie, is parameters vir die doel vasgestel. Skoon indireckte voorwerpe (op enkele uisonderings na) verskyn altyd direk na die SPIL-posisie in 'n stelsin toon 'n groot affiniteit vir voorsetsels (versa vir, aan), en kan in die koers van adjunk afgegradeer word, deur me 'n voorsetsel te verbind, en kan sodoende ook na' 'n adjunk verskyn. Direkte voorwerpe kan daarenteen nie met voorset-: sels verbind nie en kan buitendien na enige adjunk verskyn. / Language Education, Arts and Culture / M.A. (Afrikaans)

This diploma thesis is focused on the comparison of selected methods of apartment valuation in the location of Brno - Černá Pole, in specific on the apartment valuation in brick buildings. The theoretical part describes the basic notions connected with valuation, describes the methods of valuation and also the valuated location itself. The practical part deals with the apartment valuation using these methods - the method according to price provision, specifically comparative technique, then the comparative method itself but not according to price provision and finally using the yield method for an assessment of the current price. In the conclusion there is comparison of all of these used methods.