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Type 2 diabetes (T2D) is characterized by metabolic derangements that cause a shift in substrate preference, inducing cardiac interstitial fibrosis. Interstitial fibrosis plays a key role in aggravating left ventricular diastolic dysfunction (LVDD), which has previously been associated with the asymptomatic onset of heart failure. The latter is responsible for 80% of deaths among diabetic patients and has been termed diabetic cardiomyopathy (DCM). Through in silico prediction and subsequent detection in a leptin receptor-deficient db/db mice model (db/db), we confirmed the presence of previously identified potential biomarkers to detect the early onset of DCM. Differential expression of Lysyl Oxidase Like 2 (LOXL2) and Electron Transfer Flavoprotein Beta Subunit (ETFβ), in both serum and heart tissue of 6–16-week-old db/db mice, correlated with a reduced left-ventricular diastolic dysfunction as assessed by high-resolution Doppler echocardiography. Principal component analysis of the combined biomarkers, LOXL2 and ETFβ, further displayed a significant difference between wild type and db/db mice from as early as 9 weeks of age. Knockdown in H9c2 cells, utilising siRNA of either LOXL2 or ETFβ, revealed a decrease in the expression of Collagen Type I Alpha1 (COL1A1), a marker known to contribute to enhanced myocardial fibrosis. Additionally, receiver-operating curve (ROC) analysis of the proposed diagnostic profile showed that the combination of LOXL2 and ETFβ resulted in an area under the curve (AUC) of 0.813, with a cut-off point of 0.824, thus suggesting the favorable positive predictive power of the model and further supporting the use of LOXL2 and ETFβ as possible early predictive DCM biomarkers.

Aims Although there is evidence linking sugar-sweetened beverage (SSB) intake with the development of cardio-metabolic diseases, the underlying mechanisms remain unclear. The current study therefore evaluated the effects of SSB consumption by establishing a unique in-house in vivo experimental model. Main methods Male Wistar rats were divided into two groups: a) one consuming a popular local SSB (SSB- Jive), and b) a control group (Control-water) for a period of three and six months (n = 6 per group), respectively. Rats were gavaged on a daily basis with an experimental dosage amounting to half a glass per day (in human terms) (SSB vs. water). Cardiac function was assessed at baseline (echocardiography) and following ex vivo ischemia-reperfusion of the isolated perfused working rat heart. Oral glucose tolerance tests and mitochondrial respiratory analyses were also performed. In addition, the role of non-oxidative glucose pathways (NOGPs), i.e. the polyol pathway, hexosamine biosynthetic pathway (HBP) and PKC were assessed. Key findings These data show that SSB intake: a) resulted in increased weight gain, but did not elicit major effects in terms of insulin resistance and cardiac function after three and six months, respectively; b) triggered myocardial NOGP activation after three months with a reversion after six months; and c) resulted in some impairment in mitochondrial respiratory capacity in response to fatty acid substrate supply after six months. Significance SSB intake did not result in cardiac dysfunction or insulin resistance. However, early changes at the molecular level may increase risk in the longer term.

The survivor activating factor enhancement (SAFE) pathway was discovered as an alternative intrinsic pro-survival signaling pathway to the reperfusion injury salvage kinase pathway for cardioprotection against ischemia-reperfusion injury. The delineation of this pathway, made of key components such as cytokines of the immune system and transcription factors, has brought major advancements in our understanding on how the heart is able to protect itself against ischemia-reperfusion injury. In this viewpoint, we describe the major steps leading to the discovery of the SAFE pathway in small animal models to date and we discuss its translation to large animals and humans.

The Khayelitsha District Hospital (KDH) faces the difficult challenge of managing patients with high acuity penetrating cardiothoracic injuries, but without the full complement of resources to provide optimal care. At the time of this dissertation, we were unaware of the outcome of patients cared for at KDH, and of any potential modifiable risk factors that could improve their outcome. We therefore undertook a retrospective case audit to determine the outcome of patients presenting alive at our emergency unit with penetrating chest injuries (PCI). Objective: The objective of this study is to audit the KDH experience with penetrating chest injuries and to identify potential risk factors that predict outcomes in patients who sustain these injuries and require surgery at this district level hospital. The total study duration was 34 months. Methods: A retrospective review of all medical records of patients with PCI who were alive on presentation and had undergone surgery at KDH between 1st February 2012 and 31st December 2014 was undertaken .An audit was conducted on these files. During the audit, affected patient's clinical and physiological variables on admission, intra- and post-operative were collected and evaluated as potential predictors of outcome. This study also assessed a possible relationship between physiological parameters together with arterial blood gases (ABG) on presentation with immediate 48-hour mortality. The selected variables were: SBP (systolic blood pressure) 90 mmHg, palpable pulse, presence of a precordial stab wound, vascular injury, base deficit (BD) and lactate. A logistic regression analysis was performed to investigate the relationship between the selected variables and the 48-hour mortality. The relationship between fluid, BD and lactate was compared using Pearson correlation. Continuous data is presented as means ± standard deviations. Estimates for predictor variables are presented with odd's ratios (OR) and 95% confidence intervals (95% CI). Permission of this study was gained from human research ethics committee of University of Cape town. Results: Over the 34-month study period, a total of 646 patients were admitted to KDH with penetrating cardiothoracic trauma. Fifty-six patients required surgery at KDH. These results show that KDH had a PCI incidence of 5.1%, and that this was predominantly amongst males in the 15 - 24 year age group. Fifty-five patients were male and only one female. Of the 56 operated patients, 37 (66%) presented in hemorrhagic shock with SBP < 90mmHg. The mean amount of resuscitation fluid, which included both crystalloid and colloid, administered in the Emergency Room (ER) was 2481 ml per patient. Ten (17.8%) patients had a front room thoracotomy (FRT), with a mortality rate of 6 (60%). The overall mortality rate amongst operated patients was 16 (31.3%). Thirty-three patients (58.9%) had an isolated cardiac chamber injury and 23 (41.1%) had a vascular injury. Mortality amongst patients with isolated cardiac chamber injury was 5 (31.2%) and mortality among patients with isolated vascular injury was 7 (43.7%). Two patients sustained a combined cardiac and vascular injury with a mortality of 12.5%. The results of the logistic regression analysis revealed no statistically significant correlation between the selected predictors and 48-hour mortality (p-values: BP