1,721,049 research outputs found
Temporal changes in the cardiometabolic disease risk profile of the Bellville south mixed-ancestry community between 2008/09 AND 2014/16
Background/purpose: The burden of cardiovascular disease (CVD) is growing rapidly and has shifted from high-income countries to low-middle income countries, including South Africa. In the South African Mixed-ancestry population, there is a dearth of trend studies examining the changes in cardiometabolic risk factors and their behavioural, socio-demographic, and lifestyle determinants. This thesis aimed to determine the temporal changes between 2008/09 and 2014/16 in (1) absolute blood pressure levels and hypertension prevalence; (2) distribution and change in obesity or body size phenotypes; and (3) the prevalence of insulin resistance (IR), inflammatory biomarkers, and their determinants. Methodology: Participants, aged ≥20 years, residing in Bellville South and Belhar, Cape Town, were recruited in two independent cross-sectional surveys conducted during 2008/09 (N=928) and 2014/16 (N=1969). Data were obtained through questionnaires, clinical measurements (anthropometric measurements and BP), and biochemical assessments (oral glucose tolerance tests, lipid profile, and sub-clinical inflammation markers). Obesity phenotype was defined using a combination of body mass index (BMI) categories and abnormal cardiometabolic status. The latter was defined as the presence of ≥ 2 cardiometabolic risk factors. Indices used to assess IR included: insulin fasting, HOMA-IR, QUICKI, McAuley and Matsuda. Biomarkers defining sub-clinical inflammation included Ultra-Sensitive-C-Reactive Protein (usCRP) and gamma-glutamyl transferase (gamma GT). Statistical packages used for data analysis were Statistica v.13 (TIBCO Software Inc., 2017) and SPSS v.25 (IBM Corp, 2011). Measures of central tendencies and dispersion characteristics are reported to summarize survey data. The crude and age standardised prevalence of hypertension were compared across years. With regards to obesity phenotype, IR, and sub-clinical inflammation, change in the distribution was investigated using interaction tests across the years of study. Linear and logistic regression analyses adjusted for year of study, age, and gender, were applied for all three studies. Results: Participants were older in 2008/09 (54.3 years) compared to 2014/16 (49.6 years), the majority (>75%) of whom were female. Mean systolic blood pressure increased from 124 to 136 mmHg and mean diastolic blood pressure from 75 to 85 mmHg over the 7-year period. The prevalence of newly detected hypertension increased from 11.6% to 24.8% and remained significant after adjusting for confounding variables. Importantly, there was a shift in the peak prevalence of hypertension from older ages (≥ 70 years) in 2008/09 to younger individuals (40-49 years) in 2014/16. The BMI distribution between 2008/09 vs 2014/16 improved significantly with decreases in overweight (27.4% vs 23.6%) and obese (45.3% vs 42.2%) participants (p=0.001). However, across all BMI categories in both metabolic healthy and abnormal participants, anthropometric and biochemical measurements, and glucose and lipid profiles linearly increased (all p ≤ 0.018 for linear trends). Over the 7-year period, there was an increase in the prevalence of sub-clinical inflammation: us-CRP (54.7% vs 57.1%) and gamma-GT (29.6% vs 33.4%). Furthermore, multivariable analyses revealed that obesity levels, glycated haemoglobin, and fasting insulin levels were prominent risk factors associated with increased IR or subclinical inflammation, after adjusting for confounding variables. Conclusion: A significant increase in hypertension prevalence was uncovered with a rightward shift in absolute BP. The majority of these increases were amongst newly detected hypertension, suggesting a non-optimal detection of the disease. Therefore, increased awareness and screening drives for hypertension detection is crucial to reduce the prevalence of hypertension in this population group. Complications and nominal costs related to severity of hypertension must be incorporated on a greater scale than is currently practised in order to manage and prevent CVD development. A significant proportion of normal weight participants presented with metabolic abnormalities, while a substantial percentage of obese participants presented as metabolically healthy. Additional research is required to improve risk stratification for obesity phenotypes. Additionally, sub-clinical inflammation increased over the seven-year period, and was linked to strong predictors of CVDs, i.e., IR and metabolic syndrome components. Therefore, before substantial changes in CVD are observed in the population, monitoring the pathophysiological development of sub-clinical inflammation and IR biomarkers may provide early information on the trajectory of CVD burden
Risk factors of Oesophageal Cancer in South Africa
Conference Paper AbstractOesophageal cancer is one of the most fatal cancers worldwide with a five-year survival
below 15%. The incidence, histology and aetiology of oesophageal cancer vary remarkably
between and within countries as well as between ethnic groups. In South Africa the disease
affects mainly African males and the highest incidence of oesophageal cancer occurs in the
Transkei region of the Eastern Cape. Risk factors that have been reported to play a
predominant role in the aetiology of oesophageal cancer include chronic irritation to the
oesophageal mucosa, poverty, nutritional deficiencies, Human papillomavirus (HPV)
infections, alcohol and smoking. However, none of them seem to singularly account for the high incidence rates observed in several high-risk areas as well as the dramatic variations in
the frequency of oesophageal cancer in distinct geographic areas.
Infection by human papillomaviruses was first implicated in the aetiology of oesophageal
cancer in 1982. We have demonstrated the presence of low-risk HPV type 11 in subjects
with squamous cell carcinoma of the oesophagus as well as subjects with dysplasia from
South Africa. The E6 proteins of high-risk HPV contribute to tumorigenesis by interacting
with wild type p53 and induce its degradation. However, HPV type 11 is known to bind to
the p53 - carboxyl terminus without inducing its degradation
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The protective role of resveratrol against high glucose-induced oxidative stress and apoptosis in HepG2 cells
High glucose concentrations result in oxidative stress, leading to damage of cellular constituents like DNA, proteins, and lipids, ultimately resulting in apoptosis. Resveratrol, a polyphenol phytoalexin, has been studied for its potential therapeutic effects on diabetes. This study investigated the influence of high glucose (HG) on HepG2 cells and assessed resveratrol's effect on high-glucose-induced oxidative stress and apoptosis. HepG2 cells were cultured for 48 and 72 h with high glucose (40 mM), low resveratrol (25 μM), high resveratrol (50 μM), high glucose + low resveratrol, and high glucose + high resveratrol. After exposure, oxidative and apoptosis-related gene expression was evaluated using quantitative polymerase chain reaction (qPCR), and lactate dehydrogenase (LDH) release was measured using the supernatant. In HepG2 cells cultured with high glucose, all antioxidant enzymes (SOD, superoxide dismutase; GPx1, glutathione peroxidase 1; CAT, catalase; Nrf2, nuclear factor erythroid 2–related factor 2; and NQO1, NAD(P)H quinone oxidoreductase 1) were significantly reduced; however, when HepG2 cells were cultured with resveratrol (25 and 50 μM) and high glucose, the expression levels of all antioxidant enzymes were increased. The anti-apoptotic gene (B-cell lymphoma 2; Bcl2) and the DNA repair gene (Oxoguanine glycosylase-1, OGG1) were significantly decreased following high glucose exposure to HepG2 cells. Surprisingly, the expression levels of Bcl2 and OGG1 were notably elevated after resveratrol treatment. Furthermore, high glucose levels increased the LHD release in HepG2 cells, whereas resveratrol treatment reduced the LDH release. Our results demonstrate that resveratrol provides protection against oxidative stress and apoptosis induced by high glucose in HepG2 cells. Hence, resveratrol shows potential as an effective approach to address the impaired antioxidant response resulting from elevated glucose levels commonly observed in diabetes and metabolic disorders
Resveratrol attenuates high glucose‑induced inflammation and improves glucose metabolism in HepG2 cells
Diabetes mellitus (DM) is characterized by impaired glucose and insulin metabolism, resulting in chronic hyperglycemia. Hyperglycemia-induced inflammation is linked to the onset and progression of diabetes. Resveratrol (RES), a polyphenol phytoalexin, is studied in diabetes therapeutics research. This study evaluates the effect of RES on inflammation and glucose metabolism in HepG2 cells exposed to high glucose. Inflammation and glucose metabolism-related genes were investigated using qPCR. Further, inflammatory genes were analyzed by applying ELISA and Bioplex assays. High glucose significantly increases IKK-α, IKB-α, and NF-kB expression compared to controls. Increased NF-kB expression was followed by increased expression of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-β, and COX2. RES treatment significantly reduced the expression of NF-kB, IKK-α, and IKB-α, as well as pro-inflammatory cytokines. High glucose levels reduced the expression of TGFβ1, while treatment with RES increased the expression of TGFβ1. As glucose levels increased, PEPCK expression was reduced, and GCK expression was increased in HepG2 cells treated with RES. Further, HepG2 cells cultured with high glucose showed significant increases in KLF7 and HIF1A but decreased SIRT1. Moreover, RES significantly increased SIRT1 expression and reduced KLF7 and HIF1A expression levels. Our results indicated that RES could attenuate high glucose-induced inflammation and enhance glucose metabolism in HepG2 cells
Subscapular thickness is more strongly associated with blood glucose and insulin levels than waist circumference and BMI in the mixed ancestry population of South Africa.
Obesity, particularly central obesity is strongly associated with the development of
insulin resistance and type 2 diabetes. On one hand, subscapular skinfold thickness has previously
been found to be better than BMI and WC in identifying hyperinsulinemia in Asian Indian males.
Because the mixed ancestry population of South Africa is a combination of European settlers, the
indigenous Africans and the Indians we investigated the relationship between measurements of
obesity and fasting blood glucose and insulin levels in the mixed ancestry population of South Afric
Molecular genetic analysis of ceruloplasmin in oesophageal cancer
Oesophageal cancer (OC) is a disease characterized by the development of malignant tumors in the epithelial cells lining the oesophagus. It demonstrates marked ethnic variation, with squamous cell carcinoma (SCC) being more prevalent in the Black population and adenocarcinoma (ADC) occurring more often in Caucasians. The etiology of this complex disease has been attributed to a variety of factors, including an excess of iron (resulting in increased tumourigenesis), oesophageal injury and inflammation (due in part to Barrett's oesophagus and smoking among others). The aim of this study was to determine if genetic variations identified in the ceruloplasmin (CP) gene (implicated in iron homeostasis) contribute to OC pathogenesis or susceptibility. The study cohort consisted of 96 unrelated OC patients from the Black Xhosa-speaking South African population and 88 population-matched control individuals. The promoter and coding regions of the CP gene were analyzed for DNA sequence variation using heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis, restriction fragment length polymorphism (RFLP) analysis and semi-automated bidirectional DNA sequencing analysis. Fourteen previously described and four novel variants were identified. Statistically significant associations were revealed for two of the novel variants with OC in this study and could, therefore, potentially contribute to disease susceptibility. In silico analysis of the region of the promoter spanning the identified variants sought to identify putative transcription factor binding sites (TFBSs) that could possibly regulate the expression of CP. To our knowledge, this is the first study to examine CP with respect to OC in the Black South African population
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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