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    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.
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    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.
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    The effect of a high fructose diet and glucocorticoids intervention on cardiac structure and function in male Sprague Dawley rats
    (2024) Mokoena, Thobekile Sibonelo
    The impact of glucocorticoids on left ventricular (LV) morphology and function in animal models and their interaction with metabolic syndrome (MetS) remain unclear. This study aimed to determine the effects of glucocorticoids on LV structure and function and whether MetS exacerbates these effects. Male Sprague Dawley rats were assigned to control, glucocorticoids (GC), high fructose (HF) and glucocorticoids + high fructose (GC+HF) groups (n=10each). HF and GC+HF groups received a 20% fructose solution, while GC and GC+HF groups received 10mg/kg intraperitoneal injections of methylprednisolone daily for 10 weeks. After 10 weeks, LV function was assessed, and cardiac collagen content was determined. Relative wall thickness was greater in the GC group compared to the control (p=0.01). The heart weight indexed to body mass, LV weight indexed to body mass and the relative wall thickness were greater in the GC+HF compared to the control (p=0.04; p=0.009; and p=0.01 respectively). The LV end-diastolic volume was lower in the GC+HF group compared to the control (p=0.007) and the HF(p=0.01). The lateral e’ was lower in the GC and GC+HF groups compared to the control (p=0.001 and p=0.005 respectively) and HF (p<0001 and p=0.0001). The E/e’ was greater in GC and GC+HF rats compared to control (p<0.0001 and p=0.004, respectively) and HF (p<0.0001 and p=0.02, respectively). Cardiac collagen content was greater in GC and GC+HF groups compared to control (p=0.001 and p<0.0001 respectively). In conclusion, glucocorticoid administration induced cardiac remodelling, impaired LV relaxation and increased LV diastolic filling pressures. The presence of MetS resulted in concentric hypertrophy, but did not worsen LV diastolic dysfunction.
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    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.