Assessment of Thermal and Hydrolytic Stabilities and Aqueous Solubility of Artesunate for Formulation Studies.

For the purpose of establishing the optimum processing parameters and storage conditions associated with nanolipid formulations of the artemisinin derivative artesunate, it was necessary to evaluate the thermal stability and solubility profiles of artesunate in aqueous solutions at various temperatures and pH. The effect of increased temperature and humidity on artesunate was determined by storing samples of the raw material in a climate chamber for 3 months and analyzing these by an established HPLC method. Artesunate remained relatively stable during storage up to 40°C ± 0.5°C and 75% relative humidity for 3 months, wherein it undergoes approximately 9% decomposition. At higher temperatures, substantially greater decomposition supervenes, with formation of dihydroartemisinin (DHA) and other products. In solution, artesunate is relatively stable at 15°C with less than 10% degradation over 24 h. The aqueous solubility of artesunate at different pH values after 60 min are pH 1.2 (0.1 M HCl) 0.26 mg/mL, pH 4.5 (acetate buffer) 0.92 mg/mL, distilled water 1.40 mg/mL, and pH 6.8 (phosphate buffer) 6.59 mg/mL, thus relating to the amount of ionized drug present. Overall, for optimal preparation and storage of the designated formulations of artesunate, relatively low temperatures will have to be maintained throughout.

An automated drift correction method for in situ NaI(Tl)-detectors used in extreme environments.

Gamma-ray detection systems are exposed to extreme environments during in situ measurements and the NaI(TI)-detectors in these systems are frequently subjected to significant temperature fluctuations. Several elements within these detectors are sensitive to temperature deviations, which ultimately causes a drift in gamma-ray spectra. This study aimed to determine the relationship between temperature deviation and spectrum drift and found a linear relationship over a wide range of energies. It was found that an increase in the detector temperature shifts the gamma-ray spectrum to lower channels, whereas a decrease in the detector temperature shifts the spectrum to higher channels. Using this information, a novel drift correction method based on the Gaussian distribution of the 1460 keV gamma-peak of 40K was developed. Dividing the peak into five regions of interest (ROI), a weighted gain correction factor is calculated based on the comparative skewness of the measured data and the sensitivity of the drift. The detector gain is then adjusted by the same factor to correct the drift in gamma-spectrum. This method was first tested in a simulated in situ environment, followed by in situ measurements along a beach. As expected, the gain adjustments followed the trend in detector temperature. The corrected counts in each of the five bins also presented good results and a close fit to the Gaussian distribution.

Estimating indoor radon concentrations based on the uranium content of geological units in South Africa.

Very few studies have been done on radon in South Africa, even though South Africa holds nearly a tenth of the global uranium deposits. This study aimed to map and estimate the radon risk for South Africa, and to identify potential hotspots. In this study, the uranium content of the different types of rock was determined and uranium concentrations in geological units were then projected. A uranium distribution map of South Africa was then constructed, and indoor radon concentrations were estimated and mapped based on the uranium levels of areas. Towns in areas where indoor radon measurements were conducted compared well with the estimated radon values. The maps predicted high estimated indoor radon concentrations in areas at several geological structures. Towns in these areas that have not been measured were identified. The south-western and north-eastern regions of South Africa pose the highest radon risk according to this study, and extensive radon measurements in the towns of these regions is proposed.

MinION 16S datasets of a commercially available microbial community enables the evaluation of DNA extractions and data analyses.

New advances in sequencing technology and bioinformatics analysis tools have significantly supported the culture-independent analysis of complex microbial communities associated with environmental, plant, animal and human samples. However, previous work has shown that DNA extraction can have a major influence in the community profile. As such there is a constant need for new methods to efficiently and rapidly prepare and analyze DNA for microbiome research, especially in the case new and emerging technology like the Oxford Nanopore Technologies (ONT) MinION. A commercial standard was used, in triplicate, to evaluate three DNA extraction protocols, including two commercially available and one "in-house" DNA extraction method. All DNA extractions were done as per manufacturer's instructions and prepared with the same commercial ONT 16S sample preparation kit, prior to being analysed using MinION sequencing. Eight MinION 16S datasets of this microbial reference community were obtained. Reads were initially base called and demultiplexed using ONT's Guppy™ sequencing software (version 3.2.4), filtered using NanoFilt and then classified using Usearch. A set of R scripts are presented to process sintax files generated from Usearch and produce an OTU table that can be used for further analyses. All datasets were deposited into the SRA (NCBI) database. These datasets will allow future extraction kit comparisons using MinION sequencing since a standardize laboratory process using commercially available components, such as the MinION 16S sample preparation kit, microbial reference community and extraction kits, were used. The current ONT 16S workflow making use of the Epi2me agent only provides QC metrics and the ID's of the main genera identified and does not provide any tools currently for further downstream community comparison. The analyses scripts provided in the supplementary material will thus further enable the testing of new datasets against these reference sets and provide users the ability to compare their workflows with ours, thus standardizing comparisons and workflows.

Biocide resistant and antibiotic cross-resistant potential pathogens from sewage and river water from a wastewater treatment facility in the North-West, Potchefstroom, South Africa.

Exposure to antibiotics, biocides, chemical preservatives, and heavy metals in different settings such as wastewater treatment plants (WWTPs) may apply selective pressure resulting in the enrichment of multiple resistant, co- and cross-resistant strains of bacteria. The purpose of this study was to identify and characterize potentially pathogenic triclosan (TCS) - and/or, chloroxylenol (PCMX) tolerant bacteria from sewage and river water in the North-West, Potchefstroom, South Africa. Several potential pathogens were identified, with Aeromonas isolates being most abundant. Clonal relationships between Aeromonas isolates found at various sampling points were elucidated using ERIC-PCR. Selected isolates were characterized for their minimum inhibitory concentrations against the biocides, as well as antibiotic resistance profiles, followed by an evaluation of synergistic and antagonistic interactions between various antimicrobials. Isolates were also screened for the presence of extracellular enzymes associated with virulence. High-performance liquid chromatography revealed the presence of both biocides in the wastewater, but fingerprinting methods did not reveal whether the WWTP is the source from which these organisms enter the environment. Isolates exhibited various levels of resistance to antimicrobials as well as several occurrences of synergy and antagonisms between the biocides and select antibiotics. Several isolates had a very high potential for virulence but further study is required to identify the specific virulence and resistance genes associated with the isolates in question.

Surgical skills deficiencies and needs of rural general practitioners in South Africa.

BACKGROUND: At present, much of the global surgical workforce consists of non-specialist physicians (general practitioners (GPs)) whose only formal surgical training was in medical school as an undergraduate. However, there is widespread concern that GPs do not have the skills necessary to deliver essential surgical care in a rural setting. This requires that a specific training programme be developed to train rural GPs in essential surgical skills for rural settings. OBJECTIVES: To perform a critical analysis to determine essential surgical skills required by GPs in rural South Africa, with the intention of developing the content of an accredited continuing professional development (CPD) learning programme to address needs identified. METHODS: This was a descriptive study in which a desk-top review analysis and a questionnaire survey were used to obtain both qualitative and quantitative data on essential skills required for rural surgical practice. RESULTS: Of 300 GPs, 102 (34.0%) completed the questionnaire. Some of the skills listed as essential for rural surgical practice were removal of foreign objects not in the visual axis (90.0%), packing of epistaxis (93.0%), haematoma drainage (78.3%) and wound debridement and suturing (96.0%). The study also identified the outcomes and essential content of a proposed CPD programme to provide GPs in the rural setting with the required surgical skills. CONCLUSIONS: Enhancing skills of GPs in essential surgical techniques and procedures through an accredited CPD short learning programme will ensure that adequate and comprehensive essential surgical care is provided to people living in rural communities.

Triclosan resistant bacteria in sewage effluent and cross-resistance to antibiotics.

The purpose of this study was to identify triclosan tolerant heterotrophic plate count (HPC) bacteria from sewage effluent and to determine cross-resistance to antibiotics. R2 agar supplemented with triclosan was utilised to isolate triclosan resistant bacteria and 16S rRNA gene sequencing was conducted to identify the isolates. Minimum inhibitory concentrations (MICs) of organisms were determined at selected concentrations of triclosan and cross-resistance to various antibiotics was performed. High-performance liquid chromatography was conducted to quantify levels of triclosan in sewage water. Forty-four HPC were isolated and identified as the five main genera, namely, Bacillus, Pseudomonas, Enterococcus, Brevibacillus and Paenibacillus. MIC values of these isolates ranged from 0.125 mg/L to >1 mg/L of triclosan, while combination of antimicrobials indicated synergism or antagonism. Levels of triclosan within the wastewater treatment plant (WWTP) ranged between 0.026 and 1.488 ppb. Triclosan concentrations were reduced by the WWTP, but small concentrations enter receiving freshwater bodies. Results presented indicate that these levels are sufficient to maintain triclosan resistant bacteria under controlled conditions. Further studies are thus needed into the impact of this scenario on such natural receiving water bodies.

'Going rural': driving change through a rural medical education innovation.

INTRODUCTION: Medical education across the globe is in a state of flux influenced by a number of drivers for change. In response, institutions are seeking to re-align their curricula to address the prevailing imperatives. Against this backdrop, the training of practitioners for practice in rural communities was identified as an educational priority, and led to the establishment of a rural clinical school (RCS) within a Faculty of Medicine and Health Sciences in South Africa in 2011. This article describes the students' experiences in the first year that this innovative educational model was implemented and explores the extent to which it influenced their thinking and practice. METHODS: A qualitative, formative evaluation study of the first year of implementation was undertaken. Data was generated from in-depth interviews. This article focuses on individual interviews conducted with the eight students at the RCS, which explored their experiences during a year-long clerkship. Transcripts of interviews were thematically analysed. RESULTS: Four themes emerged from the analysis: a learning experience that differed from what was experienced at the tertiary training hospital, an enabling clinical environment in the district and regional hospital, the positive role played by the specialists, and the influence of the community immersion. Underlying all of the responses was the building of relationships over time both with supervisors and with patients. Evident from the responses was that students' confidence in their clinical skills and decision-making abilities was heightened while their approaches to their own learning were enhanced. CONCLUSIONS: To respond to the call for educational reform and a heightened awareness of social realities, innovative approaches to the training of medical students, such as those adopted at the RCS, are indicated. It is argued that the learning facilitated by these rural medical education models has the potential to offer learning experiences that can lead to transformation through a change in practice and attitude among the students, and ultimately also enable curricular renewal at the institutional core.

'I felt colonised': emerging clinical teachers on a new rural teaching platform.

INTRODUCTION: Studies that investigate the impact of long-term rural exposure for undergraduate medical students often focus largely on students' experiences and perspectives. Research focusing on the physician experience in clinical exposures appears to be limited. When the Ukwanda Rural Clinical School (RCS) at the Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa was implemented in 2011, the clinical specialists working at the rural hospitals were expected to take on the additional task of teaching the students in the year-long rotation. The specialists were prepared for the task through a series of workshops. The objective of this study was to explore what the implementation of the RCS meant for the practice of these physicians and to what extent the shift from full-time practising clinician to clinical teacher required them to adapt and change. METHODS: This was a qualitative study. Semi-structured interviews were conducted with lead clinical specialists who were responsible for teaching medical students in the year-long RCS rotation. Following an interpretive approach, thematic content analysis was performed to obtain a clearer understanding of how these clinicians had experienced their first year as clinical teachers in the RCS. RESULTS: Four overarching themes were identified from the interviews with the clinicians: attitudes towards the implementation of the new medical education model, uncertainty and insecurity as a teacher, emergence of the clinician teacher, and a sense of responsibility for training a future colleague. These depict in part, the journey from clinician to clinician teacher travelled during the first year of implementation. CONCLUSIONS: Embracing the role of clinical teacher enabled the development of constructive relationships between clinicians and their students with a mutual sense of responsibility for learning, patient care and improvement in clinical practice. Understanding this journey ought to influence the thinking of those considering faculty development initiatives for novice clinical teachers.

First description of the immature stages and redescription of the adults of Cosmiomma hippopotamensis (Acari: Ixodidae) with notes on its bionomics.

Cosmiomma hippopotamensis (Denny, 1843) is one of the most unusual, beautiful, and rare tick species known to the world. All stages of this species possess a unique morphology, on the one hand making them easy to identify, while on the other they exhibit similarities to certain species of Amblyomma Koch, 1844, Dermacentor Koch, 1844, and Hyalomma Koch, 1844. Adults of C. hippopotamensis have been collected on only two occasions from their hosts, namely Hippopotamus amphibius L. and Diceros bicornis (L.), and have been recorded from only a few widely separated localities in East and southern Africa. Here, the larva and nymph are described and illustrated for the first time, while the male and female are illustrated and redescribed. Data on hosts, geographic distribution, and life cycle of C. hippopotamensis are also provided.

Measuring naturally occurring uranium in soil and minerals by analysing the 352 keV gamma-ray peak of 214Pb using a NaI(Tl)-detector.

This article investigates the prospect of utilising the 351.9 keV gamma-ray of (214)Pb when determining the concentration of uranium. Soil samples were collected from various locations around South Africa and laboratory gamma ray spectra for each were obtained by means of a NaI(Tl)-detector (7.62×7.62 cm(2)). The potassium, uranium and thorium concentrations where extracted by analysing gamma ray peaks that are associated with these radionuclides. Two separate uranium concentrations were extracted; one by means of the (214)Pb decay and the other one by means of the (214)Bi decay. These uranium concentrations were compared in terms of accuracies and detection limits.

Developing an educational research framework for evaluating rural training of health professionals: a case for innovation.

BACKGROUND: World-wide, rural clinical training of undergraduate medical students is looking to transform learning experiences, calling for the adoption of innovative approaches that create spaces for curriculum renewal and new ways of thinking. In order for these teaching models to gain acceptance and credibility among the relevant academic communities, it is critical that they be studied and evaluated. AIM: This article describes an innovative rural education intervention and a concomitant, intentional process that was adopted to establish a research framework within which the intervention will be evaluated. METHODS: Key role-players participated in a one-day workshop aimed at developing the framework. A collaborative, structured process that moved through three phases of deliberation and reflection was followed. RESULTS: The documentation and raw data generated during the workshop was used to generate the framework that will serve as a blueprint for ensuring the study and evaluation of the educational innovation. CONCLUSION: Establishing an educational research framework, by adopting a consultative and collaborative process, provides a vehicle for encouraging a culture of critical accountability that seeks to discern evidence of good practice in the training of health care workers in a rural context.

Raw water quality weight factors: Vaal basin, South Africa.

Weight factors (WFs) were developed for surface raw water pollution indicator variables in Vaal River's Upper and Middle Vaal sub-basins, in South Africa. The overall objective was to formulate a quantifiable ranking system to indicate importance of pollutant variables given their established effects on human and environmental health. Multi-criteria decision analysis (MCDA) was applied to qualitative data that were obtained from South Africa's target water quality ranges as well as from literature which represented expert opinion. The human and environmental health effect choice sets were ranked from 1 to 5 on nine pollutant variable criteria: NH3/NH4+, Cl-, conductivity (EC), dissolved oxygen (DO), pH, F-, NO3-/NO2-, PO4(3-) and SO4(2-). The weighted-sum method (WSM) then assigned highest and lowest normalised weights (NWs) to F- and Cl-, respectively, for human health effects (ɛhh) alternative. Highest and lowest NWs were assigned to NH3/NH4+ and EC, respectively, for environmental health effects (ɛeh) alternative. After aggregating the ɛhh and ɛeh WFs, resultant values ranked the variables from highest to lowest as follows: F->NO3-/NO2->/NH3/NH4+>DO>pH>SO4(2-)>PO4(3-)>EC>Cl-. The results represented the importance of variables given their established effects on human and environmental health. It was concluded that WFs provided a quantifiable barometer which could signal harmful exposure to elucidate negative effects of using polluted surface raw water in the study area. The values could be incorporated into water quality models like water quality indices. The approach could be used to develop WFs for other sites, taking into account issues like the site's pollution variables of concern as well as using a ranking key constructed from established literature.

A short history of sheep scab.

The history of sheep scab is briefly discussed since it was first mentioned in 180 BC. It was probably introduced to South Africa by the early settlers and was mentioned as a problem by Simon van der Stel, although its cause was only discovered in 1809. Various measures taken over the centuries to control or eradicate the disease, which has always been of considerable economic importance, are discussed, as well as the failures and reasons why it is still with us today.

Heartwater: an abridged historical account.

Heartwater was first recognised and recorded in South Africa as early as 1838. Since then the disease has been described from almost all the countries in Africa south of the Sahara, from certain islands around Africa and from a number of islands in the Caribbean. Most of the research on the disease, at least until fairly recently, was conducted in South Africa. Progress in research on the disease has been slow but a few important findings are highlighted in this paper.

Clinical rotation in pathology: description of a case based approach.

BACKGROUND: The implementation of a system based, integrated curriculum at the Faculty of Health Sciences of Stellenbosch University, Western Cape, South Africa, resulted in less contact time for the pathology disciplines during theoretical modules, while a weekly rotation in pathology was introduced during clinical training in the fourth and fifth years. OBJECTIVE: To describe a problem based approach for this rotation. METHODS: Students are presented with a clinical "paper" case daily, integrating as many of the pathology disciplines as possible to demonstrate the interdependence of the various disciplines. They receive chemical pathology tutorials, visit the various laboratories, and receive practical training in fine needle aspiration biopsy. On the final day, the case studies are assessed and discussed. RESULTS: Most students appreciated all activities. This rotation enhanced student interactivity and autonomy and guaranteed immediate feedback. On evaluation of the rotation it was found that the students enjoyed the rotation, learnt something new, and realised the value of group work. CONCLUSIONS: This innovation integrates pathology with clinical practice and illustrates the use of laboratory medicine in the management of common diseases seen in this country. Students appreciate learning practical skills and having to request special investigations under a pathologist's supervision changes their approach to pathology requests. Familiarity with the pathology environment empowers the student to use pathology with greater ease. A bank of case studies that can be expanded to include all medical disciplines will facilitate the application of a problem based approach and enhance communication between the basic science disciplines and the clinical and pathology disciplines.

Diagnostic tools in tuberculous pleurisy: a direct comparative study.

Thoracoscopy is the most accurate yet most expensive tool for establishing the diagnosis of tuberculous (TB) pleurisy. However, most high TB-incidence regions have limited financial resources, lack the infrastructure needed for routine thoracoscopy and require an alternative, cost-effective diagnostic approach for pleural effusions. Altogether, 51 patients with undiagnosed exudative pleural effusions were recruited for a prospective, direct comparison between bronchial wash, pleural fluid microbiology and biochemistry (adenosine deaminase (ADA) and cell count), closed needle biopsy, and medical thoracoscopy. The final diagnosis was TB in 42 patients (82%), malignancy in five (10%) and idiopathic in four patients (8%). Sensitivity of histology, culture and combined histology/culture was 66, 48 and 79%, respectively for closed needle biopsy and 100, 76 and 100%, respectively for thoracoscopy. Both were 100% specific. Pleural fluid ADA of > or = 50 U x L(-1) was 95% sensitive and 89% specific. Combined ADA, lymphocyte/neutrophil ratio > or = 0.75 plus closed needle biopsy reached 93% sensitivity and 100% specificity. A combination of pleural fluid adenosine deaminase, differential cell count and closed needle biopsy has a high diagnostic accuracy in undiagnosed exudative pleural effusions in areas with high incidences of tuberculosis and might substitute medical thoracoscopy at considerably lower expense in resource-poor countries.

In situ production of gamma interferon, interleukin-4, and tumor necrosis factor alpha mRNA in human lung tuberculous granulomas.

Human tuberculous granulomas from five adults undergoing surgery for hemoptysis were analyzed by nonradioactive in situ hybridization for tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), and interleukin-4 (IL-4) gene expression. All of the patients produced TNF-alpha mRNA. Three patients stained positive for both IFN-gamma and IL-4 mRNA; the other two stained positive for IFN-gamma but not IL-4 mRNA. Heterogeneity between the granulomas was observed in those patients staining positive for both IFN-gamma and IL-4 mRNA; these patients exhibited granulomas having IFN-gamma and not IL-4 mRNA as well as granulomas positive for both cytokine mRNAs. There was no evidence of caseation in these granulomas, and the cytokine patterns may represent events in the evolution of the granuloma. However, in those granulomas exhibiting caseous necrosis, very little IFN-gamma or IL-4 mRNA was observed, implying that progression of the granuloma is accompanied by a down regulation of T-cell responses. TNF-alpha mRNA expression was highest in patients with both IFN-gamma and IL-4 mRNA. Populations of CD68 positive macrophage-like cells within the granulomas produce mRNA for TNF-alpha, IFN-gamma, and IL-4. This implies that macrophages within the tuberculous granuloma may not be dependent on T-cell cytokines for modulation of their function but may be able to regulate their own activation state and that of the surrounding T cells. These findings have implications on the delivery of immunotherapies to patients with tuberculosis.