Information needs and information-seeking behaviour of practising medical doctors at Katutura and Windhoek central state hospitals in Namibia
- Authors: Matsveru, David
- Date: 2020
- Subjects: Information behavior Information resources
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10353/17976 , vital:42000
- Description: This study investigated the information needs and information-seeking behaviour of practising medical doctors at Katutura and Windhoek Central hospitals in Namibia. Anchored on Wilson’s (1996) model of information-seeking behaviour, the purpose of the study was to establish the information required by practising medical doctors to carry out their work, how they seek information, the information sources and resources they use, and the factors that affect them as they do so. Understanding users’ information needs and the way information is disseminated in hospitals is necessary in developing an effective information provision system and ensuring the quality of information services in the hospitals. A mixed-methods research approach was used to meet the objectives of the study. Questionnaires were administered on 140 practising medical doctors at Katutura and Windhoek Central state hospitals, while fifteen doctors were interviewed telephonically, using a semi-structured interview guide. IBM SPSS (Version 25) was used to analyse quantitative data from the questionnaires, while content analysis was used to analyse qualitative data from the interviews. The findings of this research are that practising medical doctors need information mainly for improving clinical decision-making, keeping up-to-date, improving professional knowledge, and continuing education. The study also revealed that medical doctors use a variety of information sources and resources. However, the degree to which information sources are xiii used depends on the clinical context (outpatients, wards and casualty/emergency). Some contextual factors (organisational context, socio-cultural context, and information sources) can either support or hinder doctors in seeking the information they need. The patient is one of the primary information sources for medical doctors. However, language problems are a significant challenge in communicating with patients or patients’ relatives. Lack of patients’ understanding of medical terms and unavailability of properly run libraries in hospitals are some of the factors that affect doctors’ information-seeking behaviour. Participants recommended health education for patients, training of medical doctors on the use of the Internet and ICT, provision of properly run hospital libraries, and improved communication with other international hospitals as some of the ways to improve health information sources and services. Three related models were drawn from the study’s findings, based on Wilson’s (1996) model and literature, namely, the doctors’ decision-making model (DDmM), the clinical context information sources model (CCISM), and the model of information needs and information-seeking behaviour of medical doctors (MINISBMD). The thesis concludes with practical recommendations to enhance the provision of information at Katutura and Windhoek Central hospitals and suggestions for further research.
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- Date Issued: 2020
Synthesis and biological evaluation of truncated sarganaphthoquinoic acid derivatives as Hsp90 inhibitors
- Authors: Chiwakata, Maynard T
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64708 , vital:28594
- Description: Hsp90 inhibition has been at the centre of attention in current research due to the possibility of “cracking down” on the entire process leading to the development of malignant cancers. Small underlying principles common in all types of cancers have been determined that govern the transformation of normal human cells into cancerous cells, with all relying on the ATPase activity of Hsp90 protein. Hsp90 protein is therefore an attractive drug target that if successfully inhibited can result in the remission of cancer tumours by one form of treatment. To date, no Hsp90 inhibitor has been sanctioned for cancer treatment as most are still in clinical development. Our research was therefore inspired by reports that indicated the potential of quinones / naphthoquinones to act as Hsp90 inhibitors. Preliminary results of a few selected marine natural product quinone systems i.e. sargaquinoic acid (SQA) (2.47) and lapachol (3.6) showed moderate cytotoxicity and weak interactions with the Hsp90 molecular chaperone, and evidence suggested C-terminal binding of these molecules. No correlation has been determined yet between cytotoxicity and Hsp90 inhibition, hence we aimed to develop natural product inspired molecules that exhibit both cytotoxic and Hsp90 inhibition properties. Due to limited amounts of the natural product that can be acquired from natural sources, synthetic analogues were opted for. Isolation of a few selected quinones was conducted to have material that could be used in biological assays. For structural modifications, a series of truncated naphthoquinone systems were prepared adopting the sarganaphthoquinoic acid (3.5) scaffold. The naphthoquinones were prepared via Diels-Alder reactions of relevant benzoquinones with myrcene, followed by aromatization reactions using MnO2. Various alkyl and aryl amines were then coupled to the C-2/3 position of the naphthoquinone using Michael’s addition reactions. Tricyclic naphthoquinones were also synthesized from reactions with hypotaurine and citral. Design of the analogues incorporated functionalities from known Hsp90 inhibitors e.g. geldanamycin (2.28) and its analogues. Preliminary results obtained showed that coupling of naphthoquinones with aryl-amines resulted in the most cytotoxic compounds (4.14-4.19) with IC50 values as low as 0.3 μM against Hs578T breast cancer carcinoma (triple negative). Most of the alkyl amines (4.20-4.25) had IC50 values greater than 50 μM except for 4.20 and 4.21 that showed IC50 values of 7.6 μM and 2.6 μM respectively. Tricyclic naphthoquinones (4.28-4.29) showed moderate cytotoxic activity of approximately 10 μM. Hsp90 inhibition was assessed by client protein degradation assays, of which SQA (2.47), showed the best Hsp90 inhibition properties, followed by compound 4.20. The most cytotoxic arylamino-naphthoquinone (4.16) and tricyclic naphthoquinones (4.28-4.29) showed only moderate inhibition. None of the compounds led to Hsp70 induction, suggesting possible binding to the C-terminus of Hsp90. Interactions at the binding site were assessed by molecular docking studies and saturation transfer difference (STD) NMR. Docking studies were conducted on the N-terminus of Hsp90 and better binding was observed for arylamino naphthoquinones (4.14-4.19) than for other series of compounds. Unfortunately, the co-crystal structure for the C-terminus of Hsp90 is unavailable, hence docking study comparisons on both domains could not be conducted. However, STD NMR offered a platform to assess binding interactions between the naphthoquinones and the N- or C-terminal domains of Hsp90. However no interactions were observed at both the N- and C- termini of Hsp90 due to either weak binding of ligands to the protein or poor water solubility of the ligands. From these preliminary results, naphthoquinones bind to Hsp90 protein but conclusive remarks to which terminal domain they bind to could not be made. The best candidate from amongst the series of naphthoquinones prepared that showed moderate cytotoxicity and promising Hsp90 inhibition was compound 4.20. We therefore succeeded in developing a new series of naphthoquinones that possess moderate cytotoxicity and show Hsp90 inhibition.
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- Date Issued: 2015