School of Physiology (ETDs)

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Cognitive, Cardiovascular and Muscular Stress Imposed by a Twenty20 Batting Simulation
(University of the Witwatersrand, Johannesburg, 2024) Lopes, Tiago; Olivier, Benita
In the sport of cricket, batting requires prolonged cognitive control accompanied with high muscular and cardiovascular stress. However, the acuity of information processing (cognition) during bouts of physical activity is not fully studied. This investigation is the first to investigate the influence of striking rare in Twenty20 cricket on the physiology of the batter. Phase 1 a retrospective analysis of competitive individual innings in Twenty20 matches between 2006–2019. Per-delivery probabilities of run type and on/o↵-strike demarca- tion were calculated for two innings subsets. Both simulations replicate a 1-hour and 2-minute partnership of 93 deliveries, 51 of which are ‘on-strike’. The low strike rate innings replicates scoring 61 runs, compared to 88 runs in the high strike rate innings. Phase 2, a randomised, repeated measures laboratory design, recruited 14 skilled batters (competitive playing experience > 6 years) to perform both simulations. The physical (heart rate, muscular output, blood lactate accumulation, fluid loss) and cogni- tive (working memory, executive functioning, prefrontal cortex haemodynamics) strain of Twenty20 batting was quantified. High strike rate batting was found to augment responses of heart rate (p < 0.01), and produce slower sprint performance (p < 0.01). However, changes to lower-limb peak power output (p = 0.08), fluid loss (p = 0.71) and accumulation of blood lactate (p = 0.67) were comparable. Working memory response times improved with moderate e↵ects (d = 0.61) in the low strike rate simulation. Compared to large e↵ects following the high strike rate simulation (d = 1.20) where ex- ecutive functioning was moderately more error-prone (r = 0.60). The prefrontal cortex displays substantially less reserve to increase concentrations of oxygenated haemoglobin when confronted with cognitively demanding tasks following either simulation. In Phase 3, a novel device (Pitch Reaction Test - PRT) is developed to ecologically quantify response times of implicit and explicit information processing. The record- ing accuracy of the PRT was assessed using a high-speed camera. Overall, a strong relationship is observed between video footage and PRT responses ( = 0.99 0.97). Neither subject height ( = 0.01, p = 0.54) or true leg length ( = 0.00, p = 0.58) were significant predictors of PRT performance. Future studies should continue to elucidate how batting modulates information processing eciency.
Comparison of Aortic Haemodynamics in Community Participants and Patients with Systolic Heart Failure and the Impact of Blood Pressure Control
(University of the Witwatersrand, Johannesburg, 2024) Lebelo, Ntapo Marcus
In patients with systolic heart failure (HF), both decreases and increases in pulse pressure (PP) are associated with poor prognosis. If aortic PP in systolic HF is decreased due to systolic dysfunction, then improvements in stroke volume (SV) or forward wave pressure (Pf) would be beneficial. Alternatively, if hypertension is the primary cause of systolic HF, aortic PP may be increased as a consequence of high aortic characteristic impedance (Zc) and backward wave pressure (Pb), which would be detrimental. Accordingly, blood pressure (BP) lowering would be advantageous. However, the changes in central hemodynamics that accompany systolic HF are currently unclear. Hence, I aimed to assess central hemodynamics in systolic HF patients compared to community participants. I therefore compared aortic haemodynamics (central pressures [SphygmoCor], aortic tract outflow [echocardiography]), and the impact of controlled BP (SBP/DBP<140/90 mm Hg or SBP/DBP<130/80 mm Hg) between stable systolic HF patients (n=42) and age and sex-matched community participants (n=298). Systolic HF patients had lower central PP and Pb (p<0.005) and higher HR (p<0.005) than community participants. However, no other differences were noted. When assessing the impact of BP control (SBP/DBP<140/90 mm Hg), HF patients with uncontrolled BP had higher Zc (p<0.005), Pf (p<0.05), and systemic vascular resistance (SVR) (p<0.05) than both HF patients and community participants with controlled BP. Moreover, despite similar peripheral and central PP to community participants with uncontrolled BP, Zc (p<0.005) and SVR (p<0.05) were higher in HF patients with uncontrolled BP. However, when assessing more intense BP control (SBP/DBP<130/80 mm Hg), the differences in Zc, QxZc, and SVR between the systolic HF patients with uncontrolled BP and the community participants with uncontrolled BP were eliminated. In conclusion, a lower aortic PP, which was not due to decreased SV, was observed in stable systolic HF patients. However, in the presence of uncontrolled BP (SBP/DBP≥140/90 mm Hg), but not SBP/DBP≥130/80 mm Hg, Zc, QxZc and SVR were increased in patients with systolic HF. Hence, BP control and its level of control are imperative in patients with systolic HF to protect the heart from the detrimental effects of increased afterloads.
Determinant of metabolic syndrome and its cardiovascular complications among people of African ancestry
(2024) Eluwole, Omotayo Alaba
Cardiovascular disease is now a leading cause of death globally. However, metabolic syndrome is an extremely critical healthcare issue worldwide due to progressive increase in obesity and its related factors. Obesity is strongly associated with insulin resistance and other components of metabolic syndrome. There is discrepancy in the use of parameters for the diagnostic criteria of metabolic syndrome due to genetic and environmental variability in different ethnicity. Body mass index and waist circumference (WC) are commonly used in the assessment of central obesity and abdominal obesity respectively. Fahed et al observed that waist circumference was employed because measurement was easy, however, waist circumference alone is inconclusive of abdominal adiposity and must be interpreted with body mass index. The two measurements (WC and BMI) have been documented to be strongly related to insulin resistance. (Fahed et al., 2022). However, there is controversial assessment of metabolic syndrome using either waist circumference (WC) or body mass index (BMI) or waist hip ratio (WHR) or combination of two measurements (Kassi et al., 2011; Fahed et al., 2022). Our study assessed the prevalence of metabolic syndrome among apparently healthy 1516 participants from African ancestry using seven established diagnostic criteria (NCEP-ATPIII- National Cholesterol Education Program Adult Treatment Panel III, WHO- World Health Organization, IDF-International Diabetes Federation, AHA/NHLBIAmerican Heart Association/National Heart, Lung and Blood Institute, EGIR - European Group for the study of Insulin Resistance, AACE- American Association of Clinical Endocrinology). The result revealed highest prevalence of metabolic syndrome when modified NCEP-ATPIII [National Cholesterol Education Program Adult Treatment Panel III (ATP III)] was considered. The predictive assessment of blood pressure and arterial stiffness may be useful in achieving early detection and prevention of target organ damage. This study further compared clinic blood pressure, ambulatory blood pressure and central pressure using conventional blood pressure monitor, Spacelabs 90207 (Spacelabs Inc., Redmond, Washington, USA) and applanation tonometry Sphygmocor device respectively. The findings revealed that central blood pressure and ambulatory blood pressure are more predictive of cardiovascular events among people of African ancestry. Our findings are pointers to cardiovascular risk in the study population. Additionally, this study provides new insights to the role of obesity in the perturbation of left ventricular geometry of people of African ancestry with metabolic syndrome; using quantitative and comprehensive evaluation of biochemical and echocardiographic profile. Aldosterone produced locally in adipose tissue, heart, kidney and vasculature increase the expression of cytokines and other fibrotic factors. Thus, role of the local renin angiotensin aldosterone system (RAAS) in the pathophysiology of atherosclerosis and cardio-renal fibrosis was evaluated in animal study. With high prevalence of metabolic syndrome and obesity in Africans, elevated aldosterone from diet may likely predispose African community to diastolic dysfunction; this may be a pointer to increased incidence of heart failure in groups of African ancestry. Hence, this study lends insights into the potential role of TRPM7; a novel non selective cation channel and chanzyme in aldosterone-induced cardiovascular fibrosis. This study concluded that modified NCEP-ATPIII has suitable components for the diagnosis of MS in people of African ancestry. Metabolic syndrome in people of African ancestry is strongly associated with factors such as sex, smoking and alcohol. Consequently, MS and other risk factors such as obesity, aldosterone and insulin resistance may lead to left diastolic dysfunction among individuals with MS. Experimentally, aldosterone-salt induced cardio-renal fibrosis, aggravated by TRPM7 might be the underlying pathogenesis of MS and its cardiovascular complications in Africans; thus suggests TRMP7 inhibitors has potential anti-fibrotic agents.
Determination of Characteristic Impedance in a Retrospective Cohort of Coronary Artery Disease in South Africa
(University of the Witwatersrand, Johannesburg, 2024) Els, Danelle; Peterson , Vernice R.; Peters, Ferande
The relationship between coronary artery disease (CAD) and proximal aortic stiffness-induced increases in central arterial forward wave pressures (Pf) is uncertain. Using central pressure and aortic velocity and diameter measurements, we compared aortic characteristic impedance (Zc) (n=71) and central arterial pressure wave morphology (n=189) in patients with CAD to central arterial function in 210 age- and sex-matched controls from a community study. The results showed that Zc was markedly increased in patients with CAD compared to community controls (p<0.0001). In addition, after adjustment for mean arterial pressure and aortic root diameter, the early systolic pressures generated by the product of peak aortic flow (Q) and Zc (PQxZc) and Pf were markedly increased in patients with CAD as compared to controls (p<0.0001). This increase in Pf was accounted for by an enhanced PQxZc at peak PPc rather than increases in re-reflected wave pressures. Further adjustments for either brachial PP or systolic blood pressure (SBP) showed that higher Pf values were retained in the CAD patients (p<0.05, p<0.01, p<0.0001). After adjusting for conventional risk factors, peak central aortic PPc was higher in patients with CAD as compared to controls (p<0.05, p<0.005, p<0.0001). However, after adjusting for brachial SBP and confounders, central aortic PPc did not differ between the groups. Thus, increases in stiffness-associated proximal aortic Zc in patients with CAD translate into marked increases in Pf, but not peak PPc beyond brachial BP. These findings suggest that pulsatile load responsible for CAD is beyond brachial BP and poorly indexed by peak PPc.
Effects of dietary supplementation with β-sitosterol on Cobb 500 broiler chicken productivity, health and product quality
(University of the Witwatersrand, Johannesburg, 2024) Bopape, Malebogo Audrey; Chivandi, Eliton
Antibiotic use as growth promoters in chicken feeds results in antibiotic resistance and environmental pollution. To mitigate these challenges alternatives natural growth promoters are required. Beta-sitosterol is one of several phytosterols with chemical structures similar to that of cholesterol. β-sitosterol has antimicrobial, antioxidant, anti-inflammatory and hypocholesterolaemic activities, thus might replace synthetic antibiotics as a feed supplement in chicken feeds. The current study evaluated β-sitosterol’s potential to replace oxytetracycline in Cobb 500 broiler chicken feeds by determining its effects on growth performance, meat yield and quality and bird health. β-sitosterol replaced oxytetracycline at 0 (control: 50 mg/kg oxytetracycline), 500, 1000 and 1500 mg/kg feed for diet 1 to 4, respectively with doses similar in starter, grower, and finisher diets. Chickens were fed from day 1 to 42 days of age. Body mass and feed intake were measured. Body mass gain, average daily gain and feed conversion ratio were computed. Terminally, broiler chickens were fasted, weighed, humanely slaughtered and dressed. The carcass yield, viscera morphometry and plasma surrogate markers of health were also determined. Meat pH, colour, thawing and cooking loss (TL; CL), water holding capacity (WHC), tenderness and myofibrillar fragmentation length (MFL) and nutrient content were determined. Femora and tibiae mass, length, breaking strength and liver fat content and histology were determined. Dietary β- sitosterol had similar (P > 0.05) effects as oxytetracycline on the chickens’ growth performance and feed intake utilization efficiency, gastrointestinal tract (GIT) and GIT accessory viscera macromorphometry, meat yield, meat colour, pH, TL, CL, WHC, tenderness and MFL. However, breast meat crude protein content of chicken fed diet 4 was higher (P < 0.0001) compared to that of counterparts fed diets 2 and 3. Breast meat fat content of chicken fed diet 2 and diet 4 was higher (P < 0.0001) compared to that of counterparts fed diets 1 and 3. Dietary β-sitosterol had similar (P > 0.05) broiler chickens’ breast meat total saturated fatty acids (TSFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), palmitic, oleic and linoleic content as oxytetracycline. Dietary treatments had no effect on chickens’ tibiae masses and breaking strength (P > 0.05) albeit tibiae from chickens fed diet 4 were shorter (P < 0.01) than those of counterparts fed diet 2. Dietary β-sitosterol at 1000 and 1500 mg/kg feed increased (P < 0.05) liver lipid content but had no effect on hepatic microarchitecture. However, at 1500 mg/kg feed it caused micro- and macro hepatic steatosis and lobular inflammation and higher (P < 0.05) non-alcoholic fatty liver disease activity scores (NAS). Compared to control, dietary β- vii sitosterol decreased (P < 0.0001) the chickens’ malondialdehyde (MDA) concentration but increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities and glutathione S-transferase (GST) and glutathione (GSH) concentration (P < 0.05). Diet 4 increased (P < 0.01) plasma AST and GGT activities compared to diet 1 (control). At 1000 and 1500 mg/kg feed it increased plasma cholesterol concentration compared to control and β-sitosterol at 500 mg/kg feed. β-sitosterol can replace oxytetracycline as growth promoter in Cobb 500 broiler chicken diets without negatively affecting growth performance, meat yield and quality and potentially mitigates oxidative stress by upregulating systemic antioxidant enzymes activities. However, at 1500 mg/kg feed, it can increase the risk of fatty liver disease development and hypercholesterolaemia.
Effects of Supplemental Zingerone on Cobb 500 Broiler Chicken (Gallus gallus domesticus) Growth Performance, Health and Meat Quality
(University of the Witwatersrand, Johannesburg, 2023-07) Mdoda, Bayanda; Chivandi, Eliton; Lembede, Busisani Wiseman
Commercial broiler and pullet chicken producers supplement chicken diets with sub-therapeutic doses of antibiotics such as zinc bacitracin that act as growth promoters to enhance production performance, meat and egg quality. Use of these antibiotics as growth promoters, in addition to causing environmental pollution, causes the public health challenge of antibiotic resistance which compromises poultry and consumer, hence the need to search for environmentally friendly and health-friendly alternatives to antibiotics. Phytochemicals, zingerone included, display biological activities similar to those of antibiotics. This study evaluated zingerone`s potential to replace bacitracin (ZnBcn) as a growth-promoting diet supplement in broiler feed specifically determining its effects on growth performance, meat quality and bird health. One hundred and twenty unsexed 1-day-old Cobb 500 broiler chicks (10 chicks per replicate with 3 replicates per diet) were randomly assigned to four dietary treatments where zingerone replaced ZnBcn at: diet 1 – 0 mg kg-1 (control: 500 mg akg-1 of zinc bacitracin); diet 2 – 40 mg kg-1; diet 3 – 80 mg kg-1 and diet 4 – 120 mg kg-1 in the starter, grower and finisher diets. The broiler chicks were fed ad libitum for 6 weeks: starter (week 1-2), grower (week 3-4), and finisher (week 5-6). Initial and weekly body mass, daily feed intake (FI), and terminal body mass (TBM) were measured. Body mass gain (BMG), average daily gain (ADG), and feed conversion ratio (FCR) were computed. On day 42, the chickens were humanely slaughtered, blood collected and carcasses dressed. The gastrointestinal tract (GIT) and accessory GIT viscera organs were weighed and small and large intestine lengths were measured. Empty carcass masses were measured and the dressing percentages were computed. Viscera macromorphometry, long bone indices and carcass traits, the meat’s physical quality [initial and ultimate pH (pHi and pHu), colour, thawing loss (TL), cooking loss (CL), and tenderness] traits, proximate and amino acid content and fatty acid profiles were measured. Plasma malonaldehyde (MDA) concentration, glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities, surrogate markers of liver and kidney function, liver fat content and histology were determined. Across growth phases and overall, dietary zingerone had similar effects (p > 0.05) as ZnBcn on the chicken’s TBM, BMG, ADG, FI, and FCR. It also had similar effects (p > 0.05) as ZnBcn on the chicken’s empty carcass mass, dressing percentage, long bone indices and viscera macromorphometry. Dietary zingerone had similar (p > 0.05) effects as ZnBcn on the broiler chicken meat’s pHi, pHu, CL, TL and tenderness. However, at 40 mg kg-1 of feed (diet 2) it increased the meat’s redness (a*) compared to that of counterparts fed the ZnBcn-fortified control diet. Furthermore, supplemental zingerone had a similar effect to that of ZnBcn on the meat’s crude protein content but it significantly increased the meat’s ash and fat contents (p < 0.01; p < 0.0001). Meat from chickens fed diet 2 (40 mg kg-1 of feed zingerone) had the highest concentration of essential amino acids (p < 0.05) and that from chickens fed diets 3 (80 mg kg-1 of feed zingerone) had the lowest (p > 0.001) total amino acid content. Dietary zingerone had a similar (p > 0.05) effect as ZnBcn on the chicken meat’s total saturated fatty acids, but breast meat from chickens fed diets 3 (80 mg kg-1 of feed zingerone) had significantly increased (p < 0.0001) total monounsaturated fatty acid and oleic acid content. Meat from chicken-fed diet 4 (120 mg kg-1 of feed zingerone) had the highest total polyunsaturated fatty acid and linoleic acid content and a higher PUFA:SFA ratio compared to that from counterparts fed diets 1, 2 and 3. Supplemental zingerone had similar effects (p > 0.05) as ZnBcn on the chickens’ liver masses and fat contents, plasma MDA concentration, GSH-Px, GST, SOD, CAT, alkaline phosphatase, alanine transaminase activities, albumin, total bilirubin, creatinine and urea concentrations. Chickens’ hepatic inflammation and steatosis scores were similar across diets (p > 0.05). At 120 mg kg-1 of feed zingerone, though similar to the control, supplemental zingerone decreased the chickens’ plasma globulin and total protein concentration (p < 0.01; p < 0.05) compared to counterparts supplemented at low and medium dose of zingerone. Zingerone can be used as a growth promoter in place of zinc bacitracin in broiler chicken diets without compromising growth, feed use efficiency, carcass yield, long bone and GIT viscera growth and development, the meat’s pH, CL, TL and tenderness. Furthermore, it can be used without eliciting oxidative stress in the birds and with no risk to kidneys, liver and general health of the birds. Importantly, zingerone, as a dietary supplement, can be used to enhance broiler chicken meat’s redness, positively impacting its acceptability and meat’s total monounsaturated, oleic acid, total polyunsaturated and linoleic acid fatty acid profile; thus improving its nutritional value.
Factors contributing to uncontrolled high blood pressure in Ekurhuleni, Johannesburg: the community health workers’ perspectives
(University of the Witwatersrand, Johannesburg, 2024) Dawood, Zaheerah; Sekome, Kganetso
Background: Uncontrolled high blood pressure has become a concern in underserved communities of South Africa due to its consequence resulting in rising cardiovascular and cerebrovascular diseases. Community health workers at a primary care level offer door to door services for patients with chronic diseases and are often key in health education, health promotion, and disease monitoring. Understanding the voice of the community health workers regarding factors that contributes to uncontrolled high blood pressure for their patients can provide insight on strategies for future intervention programme from a systems, patient, and community perspectives. Aim: To explore community health workers' perceptions on factors that contribute to uncontrolled high blood pressure in adults living in Ekurhuleni South sub-district, Johannesburg. Methods: A descriptive, qualitative study design was used for this study. In-depth face-to- face interviews were conducted with 22 community health workers from four communities within the South sub-district in Ekurhuleni, Gauteng. The interviews focused on: the community health workers knowledge on measures used to control high blood pressure, the community health workers opinions on barriers and facilitators contributing to uncontrolled high blood pressure for their patients, and lastly their perceptions on strategies which can be used to improve the control of high blood pressure. Data analysis following thematic analysis was used in this study. An inductive approach was used to generate codes, themes, categories and to analyse the data. Results: Analysis of the qualitative data revealed six themes. Community health workers possessed knowledge regarding the symptoms, causes and complications of uncontrolled high blood pressure however, they didn’t fully comprehend the physiological concept of blood pressure and uncontrolled high blood pressure. It can be noted that the type of advises and education which community health workers provided their patients with are generally very contextualized and simple. Multiple barriers included financial, personal, social, system, medication and cultural and traditional issues. Facilitators included government and health workforce assistance, improvement of clinic accessibility, inter and intra collaboration from multiple sources such as media, other health professionals as well as patient centred approaches. Strategies to improve control of high blood pressure included improved team work, awareness creation, holistic healthcare, improved access to clinic facilities, system related improvements and patient initiatives. Conclusion: Community health workers in this study have knowledge regarding the causes, symptoms and complications of uncontrolled HBP. Multiple barriers to controlling high blood pressure included financial, social system, personal, cultural and patient barriers. The facilitators which were identified required a multidisciplinary approach. Interventions which the community health workers provide to patients are reported to be easy to follow and usually contextualized to the patient needs. Strategies required to improve the control of high blood pressure in this community are easy to implement with less assistance required from the health care system
Genetic influences on methylation of the mu-opioid receptor gene in black South African nyaope users
(2024) Masiangwako, Tsholofelo
Background: Nyaope is a highly addictive heroin derivative that elicits its effects through interaction with the µ-opioid receptor. Genetic and epigenetic mechanisms, such as mutations and (cytosine-phospho-guanosine) CpG methylation, alter the function of the mu-opioid receptor gene (OPRM1) and protein. The single nucleotide polymorphisms (SNP) rs1799971 (118 A>G) and intronic rs3778150 (T>C) in the OPRM1 have previously been associated with heroin use. The SNP 118 A>G can influence methylation levels of OPRM1 and alter mRNA and protein expression. This study compared the degree of OPRM1 methylation and frequency of SNPs 118 A>G and SNP rs3778150 in peripheral blood samples of black South African male nyaope users (n=200) to age-and-gender-matched screened controls (n=55) in a South African population. Method: DNA was extracted from whole blood samples, bisulfite converted, amplified by methylation-specific PCR and sequenced to determine individual and total methylation levels across a total of 29 CpGs within the OPRM1 promoter region (chr6: 154331689- 154332224bp). The sequencing data was analysed by each of the two methods, methylation assignment bias and partial methylation bias methods. Results: We found that the total methylation levels were lower in nyaope-users than in controls when using the methylation assignment bias method. Only CpG 29 sites showed substantial methylation in the control group in both approaches. In the partial methylation bias method, our main findings showed no differences in the total methylation levels between the two groups while most CpGs displayed significantly higher levels of partial methylation in nyaope-users while controls exhibited significantly higher unmethylation sites at some CpGs. The AG genotype frequency for SNP 118 A>G, was higher in controls than in nyaope-users while other genotypes (AA & GG) for SNP rs1799971 and (TT, CT, CC) SNP rs3778150 were broadly similar in both groups. While the TT genotype SNP rs3778150 occurred more frequently in the control group, there was no haplotype relationship between SNP rs1799971 and rs3778150. Neither was there any correlation observed between nyaope consumption and the presence of SNP rs1799971 and/or rs3778150 in the study populations. Conclusion: This study provided evidence that methylation may not be associated with nyaope addiction and that SNPs rs1799971 and rs3778150 did not alter the methylation status of the OPRM1 promoter or contribute to nyaope addiction in a black South African male population. The findings of this study are a novel contribution to the body of literature as, to the best of our knowledge, this is the first study to investigate OPRM1 gene methylation patterns and the frequency of these specific SNPs in a South African population of nyaope users.
Investigating the mechanism of action of Aristea ecklonii’s suspected antipyretic properties
(University of the Witwatersrand, Johannesburg, 2024) Muller, Miles Christopher
Aristea ecklonii (A. ecklonii) (Baker) is an indigenous, evergreen perennial medicinal plant used amongst South Africans to treat fever. This study aimed to investigate the antipyretic properties of aqueous A. ecklonii root extracts. Male Sprague-Dawley rats (250 – 300 g) received a subcutaneous (s.c.) injection of zymosan (300 mg/kg) or saline before receiving an intraperitoneal injection (i.p.) of paracetamol (50 mg/kg), aqueous A. ecklonii root extract (55 mg/kg) or saline. The i.p. injection was administered 15 h after the s.c. injection. Abdominal temperature was measured using temperature sensitive radio-transmitters. Blood, cerebrospinal fluid (CSF) and hypothalamic tissue was collected 90 min after the i.p. injection for the measurement of cytokines, prostaglandin E2 (PGE2) and enzymes involved in PGE2 synthesis. Zymosan increased abdominal temperature which peaked at 39.42 ± 0.14 °C. Compared to rats that received saline, rats receiving zymosan had increased concentrations of blood plasma IL- 1β and IL-6, increased PGE2 in the CSF and increased hypothalamic expression of COX-2 and mPGES1 (P < 0.05). Paracetamol and aqueous A. ecklonii root extract reduced the zymosan- induced fevers. Rats that received saline, followed by an i.p. injection of aqueous A. ecklonii root extract, had a decrease in abdominal temperature and an increase in blood plasma IL-1β, IL-6, TNF-α and IL-10 concentrations compared to rats that received saline (P < 0.05). Thus, the antipyretic properties of the A. ecklonii root extract seems to be related to its ability to induce systemic inflammation and not reduce the synthesis of hypothalamic PGE2 and thus should be used with caution in ill individuals.
Investigating the physiotherapy management of patients with polytrauma admitted to acute care settings and factors that influence service delivery after discharge: a Namibian survey
(University of the Witwatersrand, Johannesburg, 2024) Chirombo, Hannah E.; Van Aswegen, Helena
Introduction: Globally 5.8 million deaths per year are because of multiple traumatic injuries with as much as 16,000 deaths a day. Traumatic physical injuries thus pose a notable risk worldwide resulting in morbidity and mortality. Most commonly road traffic collisions are the largest contributing factor to traumatic physical injuries. Namibia ranks highly in Africa in the proportion of cases of motor vehicle crashes (MVC) per population and are the fifth leading cause of death. With Namibia also ranking highly on violence, many people often require rehabilitation following physical trauma. Delivery and accessibility of rehabilitation services in Namibia is hindered by a critical shortage of rehabilitation service providers employed by the state as most are attracted by the private sector. In the existing literature, auditing of usual care physiotherapy practice following polytrauma is not frequently documented. For a country with a high incidence of MVCs, it is imperative to look at usual care in physiotherapy for patients with polytrauma. Aim: To describe the physiotherapy management of patients with polytrauma in acute care settings in Namibia and the factors that influence service delivery to these patients after discharge. Methodology: A cross-sectional survey was conducted using an electronic survey tool. A study-specific questionnaire was developed, and content validation of the questionnaire was conducted by two physiotherapy experts in the field of traumatology. Convenience sampling was used to invite all registered physiotherapists practicing in Namibia’s state and/or private acute care facilities to participate (n=133). Descriptive statistics were used to summarise the data. Categorical data was summarized as frequencies and percentages and presented in tables, pie charts, and graphs. Continuous data were summarised as medians and interquartile ranges. Qualitative content analysis was done on data obtained from patients’ answers to open-ended questions. Results: Fifty-five questionnaire links were opened by the respondents; 52 responses were considered in this study yielding a 39% response rate (n=52/133). Female physiotherapists made up most of the respondents (n= 33; 64%). Most respondents were young with a median age of 30 years (IQR= 28-31) and an average of six years (IQR= 3.3-7) of clinical practice. Respondents worked in private institutions (n=18; 35%), public sector (n=16; 31%) and both public and private sector (n=18; 35%). The majority of the respondents encountered patients with polytrauma in the ICU setting and hospital ward. Most participants (n=47, 93%) reported that majority of the patients with polytrauma that they see in their places of work are males. The most frequent mechanism of injury resulting in polytrauma was motor vehicle crashes (n= 47; 93%), whilst stab wounds and gunshot wounds were rare causes of polytrauma. Frequently injured body regions were the lower limb (n=40; 77%) and head and neck (n=37; 71%). Physiotherapists commonly used breathing exercises (n=44; 85%), suctioning (n=42; 81%), manual chest therapy (n=39; 75%), body positioning to optimize oxygenation (n=38; 73%), respiratory muscle strengthening (n=35; 67%), active cycle of breathing techniques (n=34; 65%), incentive spirometry (n=34; 65%), positive expiratory pressure therapy (n=31; 60%), body positioning to aid postural drainage (n=28; 54%) and nebulisation therapy (n=25; 48%) to optimize/restore their polytrauma patients’ respiratory function. Whilst manual hyperinflation (n=32; 62%), ventilator hyperinflation (n=29; 56%) and intermittent positive pressure breathing (n=27; 52%), were ‘rarely used’. Physiotherapists frequently used early mobilisation out of bed (n=49; 94%), active range of motion (n=48; 92%), passive ROM (n=48; 92%), in bed mobilisation (n=46; 89%), and functional exercises (n=42; 81%) to restore/maintain optimal neuromusculoskeletal system function in patients with polytrauma. These techniques were immensely popular among respondents such that no one reported not using them in patient care. In the evaluation of treatment of the neuromuscular system the de Morton mobility index (n= 41; 78%), physical function in intensive care unit test (n=35; 67%) and Chelsea critical care physical assessment tool (n=34; 67%) were validated outcome measures ‘rarely used’ by most of the respondents, whilst the evaluation of muscle power (n=43; 83%), and medical research council sum score (n=43; 83%) were frequently used. Patients with polytrauma stayed between eight to 15 days and were then discharged into step-down facilities (n= 25; 48%), and subacute facilities of the same institution (n= 19; 37%) for extended care whilst some were discharged home (n= 21; 40%). Functional outcomes and hospital length of stay were factors reported to influence patients’ discharge. Respondents reported that they routinely provided home exercise programs focused on respiratory rehabilitation, cardiopulmonary endurance training, and patient and caregiver education to their patients. The lack of adequate human resources in the physiotherapy profession and insufficient knowledge by team members in Namibia about the role of physiotherapy in the care of patients with polytrauma injury were factors reported to affect in-hospital physiotherapy service delivery. Inadequate support systems for patients by their family/caregivers and the long distances that patients need to travel to access rehabilitation services after hospital discharge were factors reported to affect the continuity of physiotherapy service provision after discharge from an acute care facility. Good family support (n=11; 21%) as well as patient’s self-motivation and compliance to their treatment (n=10; 19%) were factors reported as enablers to physiotherapy service provision post-discharge. Conclusion: In Namibian acute care settings, patients with polytrauma are mostly male, sustained injury through motor vehicle crashes, and had an extended hospital stay before discharge to step-down facilities. Physiotherapy management is focused on prevention of respiratory system dysfunction and all physiotherapists prioritized active exercises and mobilisation out of bed in their patient management. Findings contribute to the limited existing body of knowledge regarding the physiotherapy management of Namibian patients who sustained polytrauma injury. The limited use of physiotherapy techniques that require adjustment of mechanical ventilator settings and the limited use of validated outcome measures by physiotherapists in their patient management are highlighted. The lack of human and financial resources are factors reported to impact physiotherapy service delivery in Namibia. Implications for clinical practice: Findings from this study provide a platform from which intervention- based studies can be conducted to better understand the effect of physiotherapy management on patient outcomes after polytrauma
Investigating the toxic effects of nyaope on the brain, liver, and kidney of Sprague- Dawley rats
(University of the Witwatersrand, Johannesburg, 2023) Mathiki, Khethani Thendo
Background. Worldwide drug use is estimated to be 345 million, encompassing both synthetic and plant-based medications, as well as both legal and illicit opioids. The use of these drugs is on the rise and is becoming a growing concern for public health. Moreover, the emergence of heroin dominant street drugs like nyaope have gained popularity, especially in low- and middle- income countries such as South Africa. The use of nyaope exposes individuals to the risk of substance use disorders (SUDs) and the array of mental health issues, as evidenced by social and clinical studies. Nyaope, a relatively inexpensive illicit drug, is commonly found in townships and outskirts of inner cities which are predominantly saturated with African/Black ethnic communities. Its composition varies depending on the geographical area but primarily consists of ingredients like heroin, opioid derivatives, rat poison, antiretroviral drugs (ARVs), and other substances. Similar to other opioids, heroin exerts its effects on the central nervous system (CNS) by acting on opioid receptors in various brain regions, including the prefrontal cortex (PFC), nucleus accumbens, and amygdala. These regions play a critical role in regulating mood and cognitive functions. Additionally, opioids undergo processing in the liver before being excreted by the kidneys. Our work sought to evaluate the effects of acute toxicity from the unique street drug cocktail known as nyaope on the behaviour and molecular markers of the PFC, liver, and kidney in Sprague-Dawley rats, despite the abundance of material already available on opioid usage. Methods. Twenty-five Sprague-Dawley rats were sourced from the Wits Research Animal Facility following ethical clearance and habituated for a duration of ten weeks. A pilot study involving three of these rats was conducted to determine the appropriate exposure dose of nyaope. Following the pilot study, the remaining twenty-two rats were divided into two groups; nyaope-treated (n=11) and saline-treated (n=11). Nyaope-treated rats received a single dose of nyaope at 0.4 mg/kg/bw and were subsequently exposed to the Open Field Test (OFT), which assesses various behavioural indices, including locomotor activity, mood, and exploratory behaviour, using the AnyMaze video tracking system. The saline-treated rats received a single dose of physiological saline at 0.4 mg/kg/bw and underwent the same 30-minute exposure to the OFT. After this exposure, the animals were placed in their respective home cages and qualitatively observed for an additional 30 minutes. Following this observation period, the rats were anaesthetized with isoflurane and euthanized exactly one hour after exposure to nyaope or saline. Tissues from the brain, liver, and kidney were collected, and RT-PCR was conducted to assess toxicity markers, including genes that code for proteins involved in the processes of apoptosis (BAX and Bcl-2), autophagy (SQSTM1/p62), microglial repair (ANXA3), and inflammation (IL-6). In addition, plasma samples were collected and analysed using IDEXX catalyst technology to examine the plasma presence of liver toxicity markers; aspartate transferase and alanine transferase, along with the kidney toxicity marker; creatinine. Results. The qualitative findings indicated that rats treated with nyaope exhibited reduced grooming behaviour. Additionally, the nyaope-treated rats experienced a phase of heightened activity followed by extreme lethargy. In contrast, the saline-treated rats displayed consistent mobility and curious behaviour. Compared to the saline-treated rats, the nyaope-treated rats exhibited clinical signs such as tremors, a rigid tail, hypoxia, and increased diuretic behaviour. When observing the track plots of the nyaope-treated rats, they tended to favour the outer zone in a thigmotaxis pattern, with few bouts into the centre, while the saline-treated rats showed more uniform movement within the OFT apparatus. Quantitative behavioural data using the AnyMaze tracking system revealed that nyaope-treated rats had decreased locomotor activity. They covered less total distance during the test and travelled shorter distances within the centre zone compared to saline-treated rats. Nyaope-treated rats also had fewer mobility episodes and moved at slower speeds on average than the saline-treated rats. In terms of mood assessment, the nyaope-treated rats spent less time mobile overall, both in the outer and centre zones and engaged in significantly fewer grooming bouts compared to the saline-treated rats. In the assessment of exploratory behaviour, it was noted that nyaope-treated rats exhibited fewer instances of rearing, line crossing, and head entries into the centre than the saline-treated rats.Regarding the molecular assessment of the brain and kidney, there were no significant differences in the expression of molecular markers between the two groups, except for a decreased expression of Bcl-2 (p < 0.001) in the kidneys of nyaope-treated rats compared withthe saline-treated rats. Additionally, plasma expression levels of AST, ALT, and creatinine were similar between the two groups. Conclusion. These findings indicate that exposure to 0.4 mg/kg/bw of nyaope for one hour does result in behavioural changes, even though it does not immediately lead to acute molecular toxicity in the brain, liver and kidney. Conversely, nyaope exposure causes a reduction in mRNA expression of Bcl-2, suggesting that the drug induces cell and tissue damage in the kidney through apoptosis
Is 24-hour augmentation index a better indicator of arterial stiffness compared to clinic augmentation index?
(University of the Witwatersrand, Johannesburg, 2024) Mukhovha, Wantonda Papinah; Maseko, Muzi
Arterial Stiffness is a major independent risk factor that is strongly associated with an increased risk of developing cardiovascular diseases (CVDs), making it an important marker in the assessment of CVD risk. Therefore, in an effort to reduce the rising incidence of cardiovascular diseases in South Africa, it is crucial to determine the best indicator for arterial stiffness. Currently two indices are used to measure arterial stiffness, pulse wave velocity (PWV) and augmentation index (AI). Since arterial stiffness measurement techniques were developed much later than blood pressure (BP) measurement techniques, important lessons can be learned from BP measurement. Studies have indicated that 24-hour BP measurement is a much better tool of measurement compared to a once off conventional BP measurement. This creates a possibility that 24-hour arterial stiffness assessment is a better tool for measuring arterial stiffness compared to a once off clinic arterial stiffness measurement. Therefore, in this study we compared 24-hour AI to in-clinic AI and also assessed gender differences. Previous studies conducted on 24-hour AI were focused on establishing normal 24-hour AI reference values. To date, no studies have been conducted to compare 24-hour AI to in-clinic AI. Moreover, gender differences in the 24-hour arterial stiffness profile have never been studied. We recruited 125 individuals of black African descent and took anthropometric measurements. We measured both conventional BP and 24-hour BP. Pulse wave analysis was performed to obtain both in-clinic and 24-hour AI. In the total population, 24-hour augmentation index (AI24) was significantly higher than in-clinic augmentation index (AIC) (p<0.0001). When participants were stratified according to gender, AI24 was significantly higher than AIC in both men (p<0.0001) and women (p<0.0001). Night-time augmentation index (AIN) in the total population was significantly higher than daytime augmentation index (AID) (p=0.0143). When participants were stratified according to gender, our results show that AIN was only significantly higher in women (p=0.0291) and not in men. Our results show that AIC may grossly be underestimating the prevalence of arterial stiffness and its adverse effects on cardiovascular target organs. Secondly, our results also show that there are gender differences in arterial stiffness fluctuations over the 24-hour period. In men, daytime arterial stiffness does not differ from night-time arterial stiffness. However, in women arteries become stiffer during the night-time compared to the daytime. These findings indicate that special attention must be given to night-time arterial stiffness because it may be more closely related to target organ damage than daytime arterial stiffness.
Isolated nocturnal hypertension and target organ damage in a population of African descent
(University of the Witwatersrand, Johannesburg, 2024) Phukubje, Edgar Matome; Maseko, Muzi
The use of ambulatory blood pressure monitoring (ABPM) has revolutionised the approach to hypertension diagnosis and management. The ability to monitor blood pressure over a 24-hour period has enabled researchers to monitor blood pressure profile away from the doctor’s clinic, which has led to the diagnosis of various hypertension phenotypes like masked hypertension, isolated nocturnal hypertension (INH) and isolated daytime hypertension (IDH), and others. Previous studies have shown that night-time blood pressure is more closely related to target organ damage compared to daytime blood pressure. Since more studies indicate that people of African ancestry have elevated night-time blood pressure compared to other population groups, nocturnal blood pressure monitoring in this population group is crucial. However, there are few studies that have investigated the prevalence of INH, and their results are inconclusive. Hence the impact of INH on cardiovascular target organ damage is not well understood in this population group. It has been reported that dietary salt intake (DSI) has more severe cardiovascular outcomes in African populations compared to non-African populations groups because they are said to be salt sensitive. However, there are no studies that have investigated the relationship between 24-hour urinary salt excretion and 24-hour dipping patterns in populations of African ancestry. In addition, the impact of INH on target organ damage has never been compared to that of IDH. Hence, current intervention strategies primarily rely on daytime blood pressure to diagnose and treat hypertension. The relationship between age and blood pressure is well understood, but current studies have mainly focused on daytime blood pressure. The impact of age on nocturnal blood pressure is not well understood in this population group, and it is also unclear whether the age-related changes in nocturnal blood pressure translate to any cardiovascular target organ changes. Therefore, the aim of this study was to determine the relationship between INH and cardiovascular target organ damage in a South African population of African ancestry. A total 1600 participants above 18 years were recruited. These form part of the ongoing South African Hypertension and Diet Study in the Human Nutrition Research Laboratory. Office blood pressure was measured conventionally and through SpaceLabs ambulatory oscillometric monitors for 24-hours. Target organ function was determined through echocardiographic measurements and applanation tonometry using the sphygmocor device. 24-hour urine samples were collected to determine electrolyte excretion rates. Blood was collected when the participants visited the clinic. Only data with complete 24-hour ABPM matched with complete urinary collections were included for data analysis and the final sample was 796 participants. v Findings from the current study showed that 11% of the participants had INH, 13% had 24- hour sustained hypertension and 4% had IDH. The three groups had different dipping patterns. The sustained hypertensive group were non-dippers, IDH group were dippers, and the INH group had two dipping patterns: non-dipping (IND) and reverse dipping (IRD). Urinary electrolyte concentrations were significantly higher in IDH, and lower in INH. The INH group and 24-hour sustained hypertensives were the oldest cohort, while the NT and IDH were youngest. Pulse wave velocity (PWV) was significantly higher in the IND and IRD. The NT and IDH group had the lowest PWV. PWV in the INH was similar but not significantly different to the 24-hour sustained HT group. These findings indicate that the two INH subtypes (IND and IRD) damage large arteries to a similar effect as 24-hour sustained hypertension, while IDH does not cause any damage. The ABPM results were used to show changes in blood pressure with age. Different age group ranges were used, in increments of 10 years. Increased nocturnal blood pressure was associated with being older. Additionally, age-related changes in nocturnal blood pressure were associated with pre-clinical diastolic dysfunction. The current findings further show that blood pressure related cardiovascular target organ damage occurs during night-time in this population group. Urine analysis showed increased excretion in IDH and sodium retention in INH. Aldosterone levels were significantly higher in the INH, compared to 24-hour sustained HT group. Low aldosterone and salt retention increased nocturnal BP in the INH group. This means the current rise in the prevalence of cardiovascular disease in people of African descent despite increased efforts to diagnose and treat hypertension, is driven by INH, which remains undiagnosed because of the over reliance on conventional blood pressure measurement
Mapping Electro-acupuncture in the treatment of lower back pain. A Scoping Review
(University of the Witwatersrand, Johannesburg, 2024) Dahya, Karishma; Hussein, Naeema; Ntsiea, Veronica
Background: Lower back pain (LBP) accounts for 7.4% of the global years lived with disability. Due to the disability associated with LBP, complementary alternative methods (CAM) are often sought after. Electro-acupuncture (EA) is a type of CAM therapy, and there is emerging evidence on its use in patients with LBP. The aim of this study was to map literature on the use of EA in the treatment of LBP. Methods: A scoping review methodology was conducted in accordance with the Johanna Briggs Institute methodology for scoping reviews. An initial search of MEDLINE and CINAHL was undertaken followed by a full search of the remaining included databases. Studies published in multiple settings from 2013 onwards that specifically looked at EA in LBP that were included which resulted in a total of (n=43) studies included in this review. Results A review of the literature showed that common treatment outcome measures included the visual analogue scale (VAS), Oswestry disability index (ODI) and the EuroQol Five Dimensions (EQ-5D). The most common parameters were 2Hz for frequency, EX-B2 for acupoints, 30 min for duration and patient tolerance for intensity. The most common comparison in this review was manual acupuncture (MA) and electro-acupuncture (EA) and most common combination treatment was EA and usual care (UC). Lastly the overall treatment outcomes (pain, function) were favourable for the use of EA in LBP. Conclusions: This scoping review mapped the information on EA in LBP from 2013 onwards. Specifically, this review showed the most common treatment parameters and outcome measures used for LBP patients treated with EA. Lastly with regards to treatment outcomes; 22 showed improvement in pain scores, 11 showed improvement in disability and function and two studies showed no change
MicroRNA expression and arterial function in type II diabetes mellitus
(University of the Witwatersrand, Johannesburg, 2024) Goldfein, Batsheva; Millen, Aletta
Background. Type II diabetes mellitus (T2DM) is a major health concern which significantly contributes to the global cardiovascular disease (CVD) burden. Arterial dysfunction is considered a subclinical marker of CVD and is associated with an increased risk of cardiovascular events. However, treatment outcomes for T2DM patients remain suboptimal, mainly due to a poor understanding and the lack of an early marker for the identification of subclinical CVD. Recently, microRNAs (miRNA), small, non-coding RNA molecules that regulate major signalling pathways through post-transcriptional modification, have been identified as possible epigenetic regulators in the development of many diseases. MiR-146a-5p, in particular, has received considerable attention as a biomarker associated with several disease states including inflammation, T2DM and CVD. However, studies surrounding the role of miR- 146a-5p in arterial function and subclinical CVD risk in diabetic populations have yielded contradictory results. Therefore, the aim of this study was to determine the role of miR-146a-5p expression in the development of arterial dysfunction in patients with T2DM. Methods. This case control study (n=118) included participants with a previous diagnosis of insulin resistance or T2DM (n=67), and a non-DM control group (n=51). Demographic characteristics and CVD risk factors were assessed using standard approaches. Arterial function was measured using applanation tonometry and SphygmoCor software. From the recorded radial and aortic waveforms, central systolic (cSBP) and pulse pressure (cPP), augmentation pressure (AP) and the forward (FWP) and reflected wave pressure (RWP) were derived using a generalised transfer function. The carotid-femoral pulse wave velocity (PWV) was measured as a marker of arterial stiffness. Using a fasting blood sample, serum concentrations of tumour necrosis factor α (TNFα) and matrix metalloproteinase 1 (MMP1) were quantified by ELISA. Real time quantitative PCR was used to determine the relative expression of miR-146a-5p using the comparative CT method relative to an endogenous control miRNA, miR-16-5p. Differences in anthropometric variables, miRNA expression and arterial function between the two groups were determined using unpaired t-tests or Mann Whitney U tests, as appropriate. Associations between miR-146a-5p expression and arterial function were determined using Pearson’s correlations. Participants were further stratified according to CVD risk using the Framingham risk score (FRS), and the associations with miRNA expression analysed using multivariate linear regression. Results. Participants with DM had significantly higher body mass index (p=0.002), triglyceride levels (p=0.004), and systolic blood pressure (p<0.001) than the control participants. Diabetic participants also had increased CVD risk compared to the control group, as assessed using FRS (P<0.001). Participants with DM also had significantly higher cSBP (p=0.003), mean arterial pressure (p<0.001), peripheral PP (p=0.04), FWP (p=0.045) and PWV (p=0.04). The relative expression of miR-146a-5p was significantly increased in the DM group compared to the control group (p=0.02). Across the study cohort, miR-146a-5p expression was significantly associated with waist-to- hip ratio (partial r=0.29, p = 0.002), triglyceride concentrations (partial r=0.2, p = 0.04), the atherogenic index (partial r=0.20, p=0.04) and TNFα concentrations (partial r=0.23, p=0.02), in age, sex and race adjusted analysis. In multivariate adjusted analysis, miR- 146a-5p expression was not associated with any of the arterial function variables (all p>0.05). However, when stratifying participants based on CVD risk, in those with a high risk for CVD (FRS≥20), miR-146a-5p was inversely associated with peripheral PP (Std β=-0.76, p=0.03, cPP (Std β=-0.76, p=0.01), cSBP (Std β=-0.38, p=0.02), FWP (Std β=-0.68, p=0.04) and RWP (Std β=-0.66, p=0.04). When MMP1 was included as a confounder, these associations were no longer significant. Conclusion. MiR-146a-5p expression was significantly higher in participants with T2DM compared to control participants and was significantly associated with traditional CVD risk factors and inflammation. MiR-146a-5p expression was not association with arterial function measures in the total population. Interestingly, in patients at a high risk for CVD, decreased expression of miR-146a-5p was associated with increased pressure pulsatility and wave reflection. These associations were lost when MMP1, a marker of arterial remodelling, was included as a confounding factor. These results suggest that miR-146a-5p may have a regulatory role in the development of arterial dysfunction through arterial remodelling in persons at high risk for CVD.
Myrmecophagous mammals in a changing world: the ecology of aardvarks and temminck’s pangolins in the kalahari
(University of the Witwatersrand, Johannesburg, 2024) Phakoago, Makabudi valery; Fuller, A.
Little is known about the distribution and ecology of the aardvark (Orycteropus afer) and Temminck’s pangolin (Smutsia temminckii) in southern Africa as they are rarely seen and difficult to study. Both species are myrmecophagous (feed on ants and termites), primarily nocturnal, 2and they tend to be solitary. Climate change, which is resulting in hotter and drier environments in most parts of southern Africa, may affect the aardvark and Temminck’s pangolin through direct impacts on the animals and through impacts on their prey resources. Understanding how climate change may impact these two myrmecophagous mammals requires us to gather further insights on how their environment and food sources are changing, how their diets overlap, how they use the environment and alter their activity to source food and buffer themselves from heat and cold, and how they are distributed across southern Africa. Previous research conducted in the semi-arid Kalahari of southern Africa showed that a decline in ant and termite populations (as indicated by counts in pitfall traps) associated with drought resulted in starvation of aardvarks and pangolins and decreased reproductive output of pangolins. Individuals of both species starved, despite previous work indicating that the diets do not overlap, with aardvark preying predominantly on harvester termites (Hodotermes mossambicus) and pangolins preying predominantly on ants (mainly Crematogaster ants). However, the research on each species was conducted at different times, so the dietary differences may have arisen from various factors that differed between the study periods. As part of a long-term project aimed at assessing the potential impacts of climate change on myrmecophagous mammals in the Kalahari ecosystem, the present study collected faecal samples from aardvark and Temminck’s pangolin at the same time in the Kalahari for one year to compare their diets and assess dietary overlap (Chapter 3). In addition to dietary analysis, the study added to our long-term data (since September 2014) of grass cover and counts of ants and termites in pitfall traps, from September 2019 to August 2022 (Chapter 2). These long-term data revealed substantial fluctuations in grass and insect availability over time, with termite populations apparently less likely to recover after drought years compared to ants (Chapter 2). The study also assessed the abundance xiii and orientation of burrows that are available to the aardvark and Temminck’s pangolin in the duneveld in the Kalahari during winter of 2021 (Chapter 4). Lastly, the study assessed the distribution and ecology of the aardvark and Temminck’s pangolin in southern Africa using freely available images and videos from Facebook and Instagram over 10 years (2010 – 2019) (Chapter 5). During the study, the study site, Tswalu Kalahari Reserve, experienced higher than average rainfall (2020 and 2021), resulting in high grass cover and an increase in the number of ants in pitfall traps, following a very hot and dry period in 2019. In contrast, termite numbers remained low. Despite the apparent low number of termites, as reflected in the pitfall traps, aardvark preferred termites over ants in their diet, and consumed predominantly termites of the genus Trinervitermes (45% of their diet) over the study period. Temminck’s pangolin preferred ants over termites and consumed mainly ants of the genus Crematogaster (42%). Although aardvarks and Temminck’s pangolin had preferences for their specific prey items, it was shown for the first time that there was dietary overlap between the two mammal species, with higher overlap when prey resources were readily available during autumn, and lower dietary overlap when prey resources were scarce during spring. The present study, however, was conducted during an unusually wet period characterized by above-average rainfall, so it is important to determine how competition for dietary items will change in hotter and drier years, when insect populations will likely be lower. Ants and termites rely on grasses for their survival; therefore, one would predict that the abundance of burrows, dug primarily by aardvark, is likely to be related to grass cover. The present study site comprised two distinct areas, differing in grass cover as a result of differences in historical grazing pressure. I therefore investigated the availability and use of burrows in the area with low grass cover and the area with high grass cover, during winter. Burrows serve as a beneficial buffer against climatic conditions for burrowing species, offering heat avoidance during the day and warmth during the night. It was found that burrow numbers were positively associated with grass cover. More burrows also were found on the western side of the dunes than on the eastern side, most likely because the xiv western side receives more direct sunlight in the afternoon, providing a warmer microclimate overnight during the cold winter. Finally, the study explored whether social media could provide supplementary information on the distribution and ecology of the aardvark and Temminck’s pangolin in southern Africa. The data, which were collected through examining photos and videos on Facebook and Instagram, confirmed that the aardvark is found throughout South Africa while Temminck’s pangolin is restricted to the northern regions of South Africa. The images also confirmed recent research that poor body condition is associated with greater diurnal activity for the aardvark, likely a response to high energetic demands of being active on cold nights. Little is known about drinking behaviour by the aardvark and Temminck’s pangolin, with only 7 records previously published for the aardvark. It was found a further 32 records for the aardvark, and 7 for the pangolin, showing that both species do occasionally drink opportunistically. The records also provided information on the predation of both myrmecophagous mammals. Predation was observed at almost all times of the year for both species, with leopard (Panthera pardus) the most common predator for the aardvark, and lion (Panthera leo) the most common predator for Temminck’s pangolin. Even though there were far fewer records of images in other southern African countries, social media appears to be a useful tool for collecting data on the distribution and ecology of the aardvark and Temminck’s pangolin. Understanding the ecology and distribution of the aardvark and Temminck’s pangolin in the Kalahari and other regions in relation to available prey resources and local climate is crucial for improving our conservation efforts of the species through informed management practices.
Neurophysiological effects of citalopram in a rodent model of ACTH-induced HPA axis dysregulation
(University of the Witwatersrand, Johannesburg, 2024) Lubbe, Andréa; Baijnath, Sooraj
Background. Major depressive disorder (MDD) is a debilitating disorder that affects approximately 300 million people worldwide. Despite multiple theories being implicated in the pathogenesis of MDD, most antidepressant drugs primarily target the monoaminergic theory of depression. Selective serotonin reuptake inhibitors (SSRIs) form a part of the most prescribed antidepressants that target the monoaminergic system. Following treatment with antidepressants, around 30% of patients with MDD continue to experience depressive symptoms, rendering them treatment resistant. The most widely accepted definition of treatment resistant depression is the resistance to at least two antidepressant regimens following the proper dose for an adequate amount of time. Treatment resistance in MDD has been attributed to dysregulation of the hypothalamic-pituitary-adrenal (HPA). HPA axis dysregulation leads to chronically high levels of glucocorticoids and failure of the regulatory negative feedback system. Consequently, there is a need for the development of novel drugs and validated animal models to study the antidepressive mechanism of these drugs. The aim of this study was to validate a rodent model of depression via chronic administration of adrenocorticotropic hormone (ACTH), and to investigate the effects of citalopram (a SSRI) on depressive-like symptoms using neurobehavioural tests and the regional brain expression of molecular markers associated with depression. Methods. Thirty-nine Sprague-Dawley rats (n=20 female; n=19 male) were randomly divided into a control group (n = 10 female, n= 9 male) and a depressed group (n=10 female; n=10 male). Rats in the control group received daily subcutaneous injections of saline (100μg/day) for two weeks. The depressed group received ACTH (100μg/day) subcutaneously daily for two weeks. Following the 2-week administration of ACTH or saline, all animals received citalopram (10mg/kg bw) for four weeks intraperitoneally, concurrently with ACTH or saline. The open-field test was performed to determine anxiety-like behaviour by assessing locomotor activity and time spent in central versus peripheral zones. The OFT was performed prior to the initiation of ACTH or saline administration. Following the 2-week administration of ACTH, the OFT was performed again to determine the effects of ACTH. The OFT was performed for a final time following citalopram treatment. The sucrose preference test (SPT) was performed to determine the presence of anhedonia. During the test, the rats were placed in the SPT apparatus with two water bottles for 12 hours. Water bottles were weighed before and after the test. After the four weeks of drug administration, rats were terminated by decapitation using a rodent guillotine. Brains were surgically removed, and the prefrontal cortex, striatum, hippocampus, and midbrain were surgically dissected and frozen. The RNA was isolated, and cDNA synthesised. Molecular gene expression analysis was performed for BDNF, CREB, TrkB, Akt, mTOR, and eEF2 using real-time polymerase chain reaction. Results. During the OFT, immobility increased in male and female saline + citalopram and ACTH + citalopram rats after 6 weeks (all p<0.05). During the SPT, females that received ACTH + citalopram had a higher preference for regular water consumption (p=0.004). In males, sucrose preference ratio was lower in ACTH + citalopram males than in saline + citalopram males (p=0.007). Regional mRNA expression of BDNF was significantly different between males and females (p<0.003). In the striatum, ACTH + citalopram females had higher expression of BDNF compared to ACTH + citalopram males (p=0.007). In the midbrain, ACTH +citalopram males had higher expression of BDNF compared to ACTH + citalopram females (p=0.01). Regional expression of mRNA of CREB resulted in a sex (p<0.0001) and treatment effect in the prefrontal cortex and midbrain (p<0.05). In the prefrontal cortex and midbrain, saline + citalopram and ACTH + citalopram males had higher mRNA expression of CREB than females (all p<0.001). There was a sex effect in the TrkB mRNA expression in the prefrontal cortex (p=0.005), as ACTH + citalopram females had a higher mRNA expression than ACTH + citalopram males (p=0.02). In the striatum, ACTH administration led to a higher TrkB mRNA expression in females compared to males (p=0.04). No significant differences were observed in mTOR mRNA expression between any of the groups (all p>0.05). In the midbrain, ACTH + citalopram females had a lower eEF2 mRNA expression than ACTH + citalopram males (p=0.02). Conclusion. This study suggest that male animals may exhibit greater susceptibility to neurobehavioural effects of ACTH, as oestrogen in females may be protective in regulating HPA axis function. Neurobehavioural changes in male rats may be linked to ACTH-induced effects on the dopamine system, affecting locomotor activity and reward processing. These results aid our understanding of the pathophysiology of depression related to HPA axis dysregulation. Nevertheless, the effects of ACTH induced dysregulation of the HPA axis on monoamine signalling, neuroinflammation, and GABA/glutamate neurotransmission, warrant further investigation
Patients’ perspectives, pain, and health-related quality of life in same-day discharge hip and knee arthroplasty
(University of the Witwatersrand, Johannesburg, 2024) Van Heerden, Martin Harry; Keller, Monique M; Lord, Sandy
Background International protocols for same-day discharge (SDD) following total hip (THA) and total knee arthroplasty (TKA) have recently been introduced in South Africa. Comparisons between recovery trajectories of THA and TKA patients in traditional length-of-stay models and SDD are limited. The impact of SDD related to pain, health-related quality of life and the patient perspective has yet to be studied in the South African context. Aim This study aimed to explore, evaluate, and compare patients' perspectives, experiences, pain, and health-related quality of life (HRQOL) following SDD after THA and TKA. Method A mixed-methods design was implemented with a collection of patient-reported outcome measures (PROMs) over six weeks (n=109: 55 THA and 54 TKA) and concluded with semi-structured interviews (n=24: 14 THA and 10 TKA). Participants scheduled for SDD THA and TKA who met the study criteria were selected through convenience sampling. Descriptive and inferential statistics were used, and a thematic analysis of interview data was conducted. Results There were significant improvements in PROMs by six weeks postoperatively in both groups. Significant between-group differences revealed persistent neuropathic pain (P=0.536) and worse health-related quality of life scores (p=0.102) in the TKA group. The themes identified highlight positive perspectives of SDD, emphasising unique challenges in the SDD TKA group. Findings indicate that patients undergoing SDD THA and TKA in South Africa produce results comparable to those in international studies. Conclusion This research advocates for a holistic approach in SDD THA and TKA, emphasising patient-centric care, effective communication, and preparation. The study contributes insights into this evolving clinical pathway and encourages further research
Prehypertension and target organ changes in an African population
(2021) Mokwena, Caroline Motheo
Hypertension (HT) remains the leading risk factor for cardiovascular diseases (CVDs) and a leading cause of death globally. It is estimated that HT causes 10.4 million deaths annually. Studies showed that even individuals who are in the normotensive( NT) range show indications of target organ damage. This gave rise to a new category of HT called pre-hypertension(pre-HT). Prior 2017, HTwas defined as a blood pressure (BP) ≥ 140/90 mm Hg and pre-HT was defined as a BP of 120 mm Hg to 139 mm Hg. In 2017 these guidelines were revised by the American College of Cardiology (ACC) and the American Heart Association (AHA). According to these new guidelines, HTis defined as BP≥ 130 mm Hg and pre-HTas BP of 120 mm Hg to 129 mm Hg. However, both the South African Hypertension Society (SAHA) and European Society of Cardiology/European Society of Hypertension (ESC/ESH) do not recommend these new guidelines. Both organisations still recommend the definition of HTas a BP ≥ 140/90. Even though the ESC/ESH guidelines are accepted by the SAHA, there is no evidence to indicate which of the guidelines are more appropriate for African communities since all the studies were conducted in western countries like the United States of America (USA) and the United Kingdom (UK). Therefore, in this study we recruited South African peoplefrom South Africa, determined the prevalence of HT and pre-HT assessed cardiovascular target organ changes.We recruited 1211 participants of African ancestry and measured both conventional and ambulatory blood pressure (ABP). To asses cardiac changes we used echocardiography to measure early-to-late diastolic filling and left ventricular wall thickness. To measure vascular changes we used the SphygmoCorto measure pulse wave velocity (PWV). Blood samples were collected to measure plasma hormone concentrations and 24-hour urine samples were collected to measure urinary electrolyte excretion. Anthropometric measurements were taken and body mass index (BMI) was calculated as weight divided by height squared. A standardised questionnaire was administered to determine intake of medication and lifestyle habits like alcohol intake and cigarette smoking. Our results indicate that the average age of the population was 44.05±18.29 years. There were more female(65%) participants than male (5%). The overall population was overweight with a BMI of 29.47±8 kg/m2. Fifteen percent (15%) of the sample population were smokers. Participants who consumed alcohol were 21%. When the AHA guidelines were used, more participants were hypertensive (41.5%) compared to those who were pre-hypertensive (18.6%). On the other hand when the ESC/ESH guidelines were used, more participants were pre-hypertensive (34.2%) compared to those who were hypertensive (25.9%). The night-time BP of the pre-hypertensives and grade-1 (HT1) was within normal range while the night-time BP of the grade 2 (HT2) and grade 3 (HT3) was elevated. The pre-hypertensives and the three HT groups had an attenuated decline in nocturnal BP. Compared to the NT, the PWV and left ventricular mass index (LVMI) of all the HT groups, including the pre-HT were significantly higher. As the HT stages progressed there was a reduction in diastolic function observed.In conclusion our results indicate that according to the SAHS/ESH that are currently applied in SA, pre-HT is overestimated while HT is underestimated. Furthermore, using the AHA guidelines, our findings indicate that cardiovascular target organ changes increase significantly fromthe pre-HTto the HT1 stage. Since both stages (pre-HT and HT1) are considered NT according to the SAHS/ESC/ESH guidelines, by the time they reach HT2 stage which is the first stage considered as hypertensive, target organ damage may have progressed significantly. Therefore, these results indicate that the AHA/ACC guidelines are more appropriate for the SA population. If these guidelines can be adopted for HT treatment, CVD target organ damage can be significantly reduced.
Review of the use of cervical cerclage at Charlotte Maxeke Johannesburg Academic Hospital
(2024) Malete, N.
Objective The aim of the study was to review the use of transvaginal cervical cerclages at Charlotte Maxeke Johannesburg Academic Hospital (CMAJH) for the period 1 June 2016 to 1 June 2017. Methods This is a retrospective review of 39 transvaginal cervical cerclages. The data collected included maternal demographic and pregnancy characteristics, previous pregnancies and outcomes, indications for the cerclages, antenatal and maternal complications, and neonatal outcomes. STATA software version 16 (Stata Corporation, USA) was used to analyse the data. Results There were 39 transvaginal cerclages, 28 (72%) of which were history-indicated (HI) and 11 (28%) ultrasound-indicated (UI). The overall live-born rate was 26/39 (67%). Seventy-one percent (20/28) and 55% (6/11) of history and ultrasound indicated cerclages culminated in livebirth respectively, however there were no statistical significance in terms of effectivity in preventing preterm birth between the two types of cerclages (p-value = 0.446>0.05). There was however higher incidence of PPROM in the ultrasound compared to the history indicated cerclage group (45.4% vs 10.7%) with a p-value= 0.05 respectively). Conclusion Transvaginal cervical cerclage remains an important intervention in the prevention of pre-term labour secondary to cervical incompetence. The use of cervical cerclage in this study resulted in a significant number of live birth rates and good neonatal outcomes regardless of the indications for the cervical cerclage.