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Design and development of a bioactive-loaded polymer-engineered neural device for potential application in reducing neurological deficits after spinal cord injuries and neuro-regeneration
(University of the Witwatersrand, Johannesburg, 2017) Kumar, Pradeep; Choonara, Yahya Essop; Modi, Girish; Naidoo, Dinesh; Pillay, Viness
Traumatic Spinal Cord Injuries (SCI), due to their devastating nature, present several interventional challenges (extensive inflammation, axonal tethering, scar formation, neuronal degeneration and functional loss) that need to be addressed before even a slight neuronal recovery can be achieved. Recent post-TSCI investigational approaches include support strategies capable of providing scaffold architecture to allow axonal growth and conformal repair. This research provided detailed insight towards the development and fabrication of six specialized Polymer-Engineered Neural Devices (PENDs): 1) poly(lactic-co-glycolic acid)-gliadin (PLGA-GLDN) nanofibrous mats, 2) polyacrylamidated chitosan (PAAm-g-HT) scaffold, 3) functionalized chitosan methoxypolyethylene glycol (CHT-mPEG) cryosponges, 4) polyacrylonitrile-elastin-collagen (PANi-EC) neurosponge, 5) methylcellulose-alginate-polyethylene glycol (MAP) thermogel, and 6) chitosan-luronic F127-β glycerophosphate (CHT-PF127-βGP) composite thermogel for potential restriction, repair, regeneration, restoration and reorganization post-SCI. The latest trends in biomaterials-based SCI intervention were reviewed, discussed and analyzed in detail throughout the thesis. The research also involved an in silico analytico mathematical interpretation of multi(biomed)material assemblies wherein quantification of energy surfaces and molecular attributes via atomistic, dynamic, and docking simulations was carried out. The in silico experimentation additionally confirmed the potential of curcumin as a bioactive of choice for SCI intervention. Curcumin and dexamethasone were incorporated into the compact scaffolds and the bioactive release was determined over a period extending up to 60 days. The PLGA-GLDN nanofibrous mats demonstrated the formation of a compatible blend among the component polymers at equal weight ratios (PG55) as confirmed by quantitative physicochemical characterizations. Image processing analysis (DiameterJ plug-in of ImageJ) was performed on the SEM images of nanofibers to quantify the size, porosity, and orientation of the samples. Nanofibers within the size range of 10nm and 250nm were obtained in case of compatible blend and the nano stack was used for in vivo implantation post-SCI. Polyacrylamidated chitosan (PAAm-g-CHT) was synthesized via a unique persulfate-mediated polymer slicing and complexation as determined by static lattice atomistic simulations. The graft copolymer so obtained was fabricated into an anisotropic neurodurable scaffold. The CHT/mPEG cryosponges showed unique morphological features such as fringe thread-like structures (CHT alone); hemispherical, pebble-like structures (CHT-mPEG); curved quartz crystal-like or crystal-flower-like structures (CHT-mPEG-CHO); and grouped, congealed, steep-sided canyon-like structures (CHT-mPEG COOH). A novel image processing protocol involving DiameterJ and ND plugins of ImageJ software was employed for analyses of the SEM micrographs in terms of % porosity, pore wall thickness and % xiiehaviorxii of the porous scaffolds. The PANi-EC interpenetrating polymer network neurosponges were synthesized employing free radical polymerization under acidic conditions wherein first-in-the-world spinomimetic scaffolds were obtained. The unique feature of the PANi-EC neurosponge was the formation of a fibrous neurotunnel architecture mimicking the native spinal cord. The physicochemical characterization revealed that the secondary structure of the peptide molecules (elastin and collagen) rearranged in the presence of PANi to their native extracellular matrix (ECM) form confirming the self-assembling nature of the polymer-peptide architecture. Furthermore, the PANi-EC neurosponge provided a perfect balance of matrix resilience and matrix hardness similar to the native collagen-elastin complex in vivo. Two very interesting tri-component thermogels were reported here viz. a simple blend thermogel comprising methylcellulose, sodium alginate and poly(ethylene glycol) and a complex thermogel incorporating chitosan, Pluronic F127 and β-glycerophosphate. Both the thermogels solidified at physiological temperature confirming their applicability in vivo. The outstanding feature of MAP thermogels was the formation of hydrogen bonded O-H…C=O which only formed in the tripolymeric blend while the bipolymeric blends showing no such interaction. We proposed that the MAP thermogel self-assembled into a repeating network structure represented by “PEG400-ALG-hydrophillicMChydrophobic}-{hydrophobicMC-hydrophilic}-ALG-PEG400” and the physical “compression” might have led to the formation of hydrogen bonded O-H…C=O among MC/alginate or PEG/alginate in the presence of PEG or MC, respectively. In case of the complex CHT/PF127/βGP thermogel, a unique triphasic gel-sol-gel transition xiiehavior was observed with the thermogel forming a gel-phase at lower temperatures (T<20°C), a sol-phase at intermediate temperatures (20°C35°C). The MTT proliferation studies indicated that all polymer engineered neural devices (PANi-alone matrix) were capable of efficiently supporting the growth of PC12 cells compared to the control over a period of 72 hours. The fundamental objective of this thesis was to test the applicability and capability of various biomaterial composites towards the repair and regeneration of neuronal tissue after traumatic spinal cord injury. Although drug-loaded scaffolds were also developed, only drug-free scaffolds (PLGA-Gliadin 5:5 electrospun nanofibers; PANi-Elastin-Collagen neurosponge; and Chitosan/Pluronic F127/β-glycerophosphate thermogel) were tested in vivo for the proof-of-concept. The 21-point scale BBB locomotor rating analysis demonstrated that PEND I (14), PEND II (19) and PEND III (18) provided significant motor recovery as compared to the lesion-control (5) group 28 days post-SCI and –implantation. The immunohistochemistry confirmed that reparative changes were accompanied by marked upregulation of iNOS, a notable influx of ED1-positive chronic inflammatory cells, the appearance of multinucleate cells characteristic of presumptive regenerative neuroblasts and near-complete loss of GFAP and NF-200 protein/structural integrity. Almost complete functional and neurostructural recovery was observed with post-SCI implantation of PEND II and III. In conclusion, the composite scaffolds tested in this research demonstrated immense potential in improving the neurological, neurochemical, and behavioral outcome after implantation post-SCI.
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Comparing health inequalities in maternal health: An analysis of the South African Demographic and Health Surveys (SADHS) 1998 and 2016
(University of the Witwatersrand, Johannesburg, 2023-09) Holden, Celeste Claire; Blaauw, Duane
Background: Inadequate access to maternal health services (MHS) is directly linked to maternal and neonatal mortality and morbidity. South Africa (SA) is known to be an unequal society. Researching and documenting the utilisation and access to MHS can assist in the appropriate redirection of services to ensure equitable service delivery. The study identifies differences in MHS access between ethnicity groups, residence, province, maternal education level and household wealth quintile. The study quantifies the inequalities in access to MHS in SA in 1998 and 2016, and then evaluates the change in inequalities between the two periods. Methods: Data was analysed from the 1998 and 2016 South African Demographic and Health Surveys. First. the study identifies differences in MHS access between ethnic groups, residence, province, maternal education level and household wealth quintile using regression analyses. Then, the inequalities related to access of MHS in 1998 and 2016 are calculated using the relative (RII) and slope (SII) index of inequality and the concentration index (CI). Lastly, the inequalities between 1998 and 2016 were compared using generalised linear models, indicating whether inequalities increased, decreased, or remained the same. All analyses were done in Stata and adjusted for the multistage-stratified sampling of the surveys. Results: Utilisation of MHS in SA varies between different groups based on ethnicity, residence, province, mothers’ education level, and wealth quintile. In 1998 and 2016, Black/African women have the least utilisation of all MHS. A clear pattern is seen where women with higher education and high wealth quintile, have increased MHS utilisation. In most cases, the inequalities narrowed between 1998 and 2016 for all MHS. However, inequalities are still present in 2016 for many MHS. For example, using simple inequality measures, the largest inequalities in 2016 are seen between women of different ethnicities accessing four or more antenatal visits (ANC4), where there is a 11.1 percentage point difference between the highest group (White & Indian/Asian) and the lowest group (Black/African). For complex inequality measures, there are still significant relative and absolute inequalities in antenatal visits in 2016 for maternal education (RII: 1.25; SII: 1.14) and household wealth quintile (RII: 1.23; SII: 1.11). Conclusions: Between 1998 and 2016, population-level utilisation to MHS increased in all MHS and the majority of within group inequalities narrowed over time. However, inequalities still exist in all maternal health outcomes. SA has implemented multiple programmes and policies to address inequalities in MHS and decrease maternal mortality and morbidity. However, these need to be continuously monitored and evaluated based on the latest data to ensure that efforts are going towards addressing the specific groups where inequalities are still present.
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Experiences of healthcare workers using the AwezaMed translation application in antenatal settings
(University of the Witwatersrand, Johannesburg, 2023-06) Cason, Caroline Marian; Slemming, Wiedaad; Wilken, Ilana
Introduction: Language barriers impede quality health care service in South Africa. Trained interpreters could alleviate this problem, but they are not employed in public or private health settings. Health care workers rely on informal interpreters, who do not necessarily provide an adequate service, and may be resentful of this extra task. AwezaMed is a smart application developed by the Council for Scientific and Industrial Research (CSIR) with content developed for maternal health settings. The aim of this study was to assess usability and user experience relating to AwezaMed. Methods: A user experience study was conducted using mixed methods. The systems usability scale (SUS) was employed, surveying 12 users, to generate a quantitative score, representing the overall usability of the system. Interviews were conducted with 14 users and analysed thematically to identify themes of usability and user experience, and recognise factors which contribute to use of the application. Results: The application (app) achieved a total score of 66.25, rating it between ‘OK/Fair’ and ‘Good’. Understandability, operability, attractiveness, and trust were important usability themes. Users also reported using the app as an aid to language learning. Factors which influenced the use of the app included previous experience with mHealth, experiencing a language barrier in health settings, and unavailability of, or problems with interpreters. Discussion: While the app was received positively, it did not meet users’ expectations, as two-way communication could not be achieved. Due to the often-strained relationship between healthcare workers and informal interpreters, there remains a demand for a usable, trustworthy mHealth solution. A framework is proposed, based on these findings, to evaluate mHealth translation applications in South Africa in the future.
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Reporting Silica Dust Exposure Measurements in South African Gold and Coal Mines: 2005 to 2016
(University of the Witwatersrand, Johannesburg, 2023-10) Mongoma, Brian Tshepo; Nelson, Gill; Brouwer, Derk
Background: Arising from the Mine Health and Safety Act 29 of 1996 (MHSA), one of the measures to protect mine workers is monitoring exposure to airborne pollutants. Mines are statutorily required to report airborne pollutant concentrations to the Department of Mineral Resources and Energy (DMRE) on a regular basis. Based on the DMRE's 2013 report, it was determined that 76% of workers were exposed to airborne pollutants at concentrations less than 10% of their respective occupational exposure limits (OELs). Using the same exposure data from the DMRE, the Chamber of Mines of South Africa reported a 14% improvement in the exposure to the airborne pollutants from 2005 to 2013. However, these reported reduced exposures to airborne pollutants are based on the summation of all airborne pollutant exposures by the DMRE. The annual reports refer to the percentage of employees exposed to the combined airborne pollutants, rather than to specific pollutants, such as silica dust – a hazard that is high on the occupational health agenda of the mining industry. From these reports, broad (and perhaps incorrect) conclusions are reached with regard to trends in silica dust and other exposures. The limitations of the SAMI include inaccurate data, self-regulation, incomplete employment and exposure records, and historical biases, which hinder its ability to effectively handle occupational health risks. This emphasizes the immediate need for clear and consistent regulations, accurate data collection, and impartial research approaches to protect the health of mine workers. Objectives: The objectives of this study were to describe trends in combined airborne pollutant and silica dust concentrations from 2005 to 2016, and to evaluate the DMRE Mandatory Code of Practice (MCoP) and the EN 689 methods (for testing exposure levels in the workplace against the OEL of 0.1 mg/m3) as published by the European Committee for Standardization (CEN), using reported silica dust concentrations from 2015 and 2016. Methods: This was a cross-sectional study in which secondary airborne pollutants exposure data, reported to the DMRE by coal and gold mining members of the Minerals Council, were analysed. The 282 870 data points were pooled together to describe trends in airborne pollutant exposures as they comprised 69 airborne pollutants reported by different mines with various mining methods, activities, and occupations. The exposure data was categorized into coal and gold mines, and further into four three-yearly periods (i.e. period 1: 2005-2007, period 2: 2008-2010, period 3: 2011-2013, and period 4: 2014-2016). This was conducted in order to have a consistent metric to allow for uniform assessment across different pollutants with varying OELs. Dividing the exposure concentration by its OEL provided a ratio, similarly to the way that an Air Quality Index is calculated. As a result, the data was normalized by dividing each pollutant exposure concentration by its occupational exposure limit (OEL) to obtain a ratio, termed Q. The arithmetic mean, standard deviation, geometric mean, and geometric standard deviation of the Qs were calculated for each of the three groups i.e. coal and gold mines combined, b) coal mines, and c) gold mines, for each period. Jeffreys’s Amazing Statistics Program was used to analyse the Qs and silica dust concentrations. The Kruskal–Wallis test was used to identify statistically significant differences among the four time periods for each commodity group. Additionally, Scheffe’s post-hoc test in JASP was conducted for further analysis and comparison of differences across all observed periods. Two methods, namely the EN 689 and the method required by the DMRE MCoP, were used to assess compliance. EXPOSTATS Tool 1 was used to calculate the arithmetic mean (AM), median, standard deviation (SD), geometric mean (GM), geometric standard deviation (GSD), and 90th and 95th percentiles of the exposure data derived from EN 689. Microsoft Excel was used to calculate the 90th and 95th percentiles of the exposure data based on MCoP method. A total of 127 014 silica dust data points from 2005 to 2016 out of the 282 870 were utilized to describe silica dust exposure trends, and 44 990 data points from the 127 014 were used to assess compliance for the years 2015 and 2016. Results: A total of 282 870 personal airborne pollutant concentrations from 2005 to 2016, obtained from DMRE, were included the analysis. Analysis of the pooled airborne pollutant exposure concentrations indicated that there was a high variability (data points were far apart and also far from the GM) as the GSDs ranged from 6.37 to 7.53, 7.8 to 8.43, and 5.7 to 6.16 for the coal and gold mines combined, coal mines alone, and gold mines alone, respectively. The variabilities of the silica dust concentrations were less than that of the pooled airborne pollutant data. The GSDs of the silica dust concentrations were < 3.5 for all three groups compared to the GSDs calculated from the pooled airborne pollutants concentrations, where the lowest GSD was 5.7. The trends in the pooled airborne pollutant exposure concentrations over the 12-year period, for all three groups, showed that there was a reduction in reported exposures to combined airborne pollutants. The AMs of the ratios (Q) indicated that the reduction in exposures for coal and gold mines combined, gold mining alone and coal mining alone, were 57%, 55% and 26%, respectively. The corresponding GMs of the ratios (Q) for gold mining alone, coal and gold mines combined, and coal mining alone, reduced by 64%, 45% and 15%, respectively, from 2005 to 2016. The distribution of the airborne pollutant data was skewed, which affected AM more than GM, and resulted in differences between the two measures. This was evident in the gold mining data, where the AM decreased by 55% but the GM decreased by 64%. Data for the period 2005-2007 had the highest AM (1.54) and standard deviation (2.75), suggesting that there were outliers. In this period, ratios (Q) ranged from 0.003 to 7.7, impacting the AM and creating a gap between median and AM values. From 2008 to 2010, the AM (1.26) and SD (2.04) decreased, showing reduced variability. A similar trend was observed from 2011 to 2013, with increased numbers of observations and further reduced variability. In 2014-2016, the AM decreased to 0.67 and SD to 1, indicating stability. The GMs for the coal and gold mines combined, coal mines alone and gold mines alone ranged from 0.17 to 0.31, from 0.22 to 0.28, and from 0.16 to 0.45, respectively. The trends in reported silica dust concentrations in all three groups showed a reduction over the 12-year period. The AMs indicated that the reductions for coal and gold mines combined, gold mining alone and coal mining alone, were 61%, 38% and 34%, respectively. The GMs of the silica dust concentrations indicated that the reductions in exposures for coal and gold mines combined, coal mining alone, and gold mining alone, were 54%, 35% and 31%, respectively. The AMs of the silica dust concentrations for coal and gold mines combined ranged from 0.17 to 0.44 mg/m3, while the coal mines ranged from 0.67 to 1.02 mg/m3 from 2005 to 2016. For gold mines, the AMs ranged from 0.13 to 0.23 mg/m3. Similarly, the GMs of the silica dust concentrations for the coal and gold mines combined ranged from 0.11 to 0.24 mg/m3, whereas coal mines ranged from 0.41 to 0.63 mg/m3, and gold mines ranged from 0.09 to 0.13 mg/m3. The 90th percentiles for the silica dust concentrations almost correlated with the AMs as they reduced by 67%, 40% and 34% for coal and gold mining combined, gold mining alone, and coal mining alone, respectively. The 90th percentiles for silica dust concentrations for the coal and gold mines ranged from 1.64 to 2.48 mg/m3, and 0.29 to 0.51 mg/m3, respectively. Although the trends indicated a reduction in exposure to silica dust concentrations, the AM, GM, 90th and 95th percentiles exceeded the OEL of 0.1 mg/m3 for the entire study period for the three groups, except for the gold mines alone in 2016. In that year, the GM was 0.09 mg/m3 (rounded to 0.1 mg/m3). For coal mining only, the 90th percentiles ranged from 1.64 to 2.48 mg/m3, whereas the 95th percentiles ranged from 2.16 to 3.16 mg/m3. For gold mining only, the 90th percentiles ranged from 0.29 to 0.51 mg/m3, and the 95th percentiles ranged from 0.35 - 0.63 mg/m3. A total of 44 990 silica dust concentrations were used from 2015 to 2016 to compare the 95th percentiles according to EN 689, and the 90th percentiles according to the MCoP. The DMRE MCoP method was shown to underestimate the exceedance of the occupational exposure limit by 5-26%, when compared with the EN 689 method. Conclusion: Despite the variabilities and challenges associated with pooling the airborne pollutants concentrations in the coal and gold mining industries, exposures to the airborne pollutants in the three commodity groups decreased from 2005 to 2016. However, reporting employee exposure as pooled airborne pollutants concentrations is flawed and obscures exposures to individual pollutants such as silica dust. The three commodity groups showed a decrease in silica dust exposure measurements from 2005 to 2016. However, there was still overexposure to silica dust in the three groups (greater than the OEL of 0.1 mg/m3). Inhalation of particles containing silica was higher in the coal than the gold mines, which is contradictory to what is known about the silica content of the ores in which the two commodities are found. The DMRE MCoP approach to compliance with silica dust levels underestimated the exceedance of the OEL in comparison to the EN 689’s approach. The current DMRE reporting methodology, i.e. the pooling of all data, does not allow accurate reporting of silica dust exposures and as a result, it does not provide direction or support for carrying out measures to decrease exposure to silica dust. The MCoP method for compliance testing revealed higher 90th-percentiles for coal mining compared to the 90th-percentile estimated for the population (EN 689). For gold mining it was the opposite. The EN 689 method is a more precise means of estimating OEL compliance, which is crucial for managing silica dust and specific pollutant health hazards and should be used in favour of the method in the MCoP.
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Minimising the risk of thermally induced cracking in mass concrete structures through suitable materials selection and processing
(Springer, 2018) Ballim, Yunus
The hydration of cement is an exothermic reaction which generates around 300 kJ/kg of cement hydrated. In mass concrete structures such as dams and large foundations, this heat of hydration causes a significant rise in temperature in the internal sections of the concrete. If thermal gradients between the internal sections and the near-surface zone of the concrete element are sufficiently large, the thermal stress can cause cracking of the concrete. This cracking may cause functional or structural problems in the operation of the structure. In order to minimise the potential for such cracking, it is necessary to minimise the rate and amount of heat that is evolved, particularly during the early period of the hydration process. This can be achieved by design engineers and concrete technologists through judicious selection and processing of concrete-making materials. This paper presents the observations and results obtained over a number of years from adiabatic testing of concretes, computational modelling of temperature development in large concrete structures and direct temperature measurements in actual structures, with a view to understanding the effects of concrete-making materials on temperature development in concrete. The paper considers the effects of different types of rock aggregates, different types of Portland cement, fineness of grinding of the cement, the addition of supplementary cementitious materials and variations in the concrete starting temperature on temperature development in a large concrete element over time. The results indicate that using a coarser ground cement, adding significant amounts of supplementary cementitious materials and cooling the concrete mixture before placing has a more significant effect in reducing the risk of cracking than varying the aggregate type of the Portland cement type.