Cardioprotective effect of remote ischaemic preconditioning and the role of Early growth response-1 as a master switch regulator

Once the blood supply is restored after heart attack by opening up the coronary artery, the heart is insulted by ischemia-reperfusion (I/R) injury. Direct ischaemic preconditioning has the ability to protect the heart against this injury for a brief period of time. Direct ischaemic preconditioning involves cycles of non-lethal occlusion of the coronary artery and releasing. Preconditioning other organs remote to the heart such as the limbs can protect the heart from I/R injury. This new therapeutic technique, known as remote ischaemic preconditioning (RIPC) is non-invasive and easy to apply compared to direct ischaemic preconditioning. However, we still do not know the mechanism through which RIPC protects the heart. This thesis explores the underlying mechanism of RIPC-induced cardioprotection from myocardial I/R injury, in experimental in vitro and in vivo models. Both intrinsic and extrinsic pathways of apoptosis contribute to cell death during heart attack. This thesis explores the relative contribution of the apoptotic pathways in I/R injury. Moreover, autophagy is associated with myocardial I/R injury sparing effect of direct ischaemic preconditioning and postconditioning. It is hypothesized that autophagy plays a key role in RIPC-mediated cardioprotection and autophagy stimulation provides therapeutic benefit. There is evidence that preconditioning can decrease the level of early growth response-1 (Egr-1), a master regulator highly expressed in heart tissue followed by heart attack. Once Egr-1 is highly expressed, a number of downstream inflammatory signalling molecules get expressed, which are well known to cause myocardial damage. It is shown that Egr-1 downregulation in the hind limb prior RIPC abolishes RIPC-induced cardioprotection. In addition, it augmented certain a number of process that are attenuated by RIPC including apoptosis, cytokine expression. This work identifies a key role for Egr-1 in the signalling mechanism of RIPC through its regulation of a number of crucial downstream genes and cardioprotective pathways. In addition, it identifies IL-6 as a potential mediator of RIPC to mitigate myocardial I/R injury

Repurposing waste pozzolans for cleaner mortar production: Mechanical and durability properties with microstructural behavior

This study explores three waste-derived supplementary cementitious materials (SCMs)—volcanic ash (VA), egg shell (ES), and rice husk ash (RHA)—as partial replacements for ordinary Portland cement (OPC) in the mortar at 0%, 5%, 10%, 15%, and 20% replacement levels. Thirteen mortar mixes were evaluated based on physical, chemical, fresh, mechanical, and durability properties, as well as high-temperature performance, failure modes, microstructural, and cost analyses. The results showed compressive strength improvements of 8.2% with VA and 7% with RHA at 5% replacement, while ES achieved a 16% increase at 10%. Elevated temperatures reduced compressive strength by up to 87%. Flexural strength increased by 15% for VA, 43% for ES, and 21% for RHA. All SCMs met ASTM C618-22 criteria for natural pozzolans. Optimal replacement levels were 5% for VA, 10% for ES, and 5% for RHA. Overall, ES at 10% demonstrated superior strength despite higher water absorption, highlighting their eco-friendly potential.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author

COVID-19 and Coronary Heart Disease

Coronary heart disease (CHD) is the leading cause of mortality worldwide. One of the main contributions of mortality and morbidity in CHD patients is acute myocardial infarction (AMI), which is the result of abrupt occlusion of an epicardial coronary artery due to a sudden rupture of atherosclerotic plaque, causing myocardial ischemia. In the initial stage of myocardial ischemia, lack of oxygen and nutrient supply results in biochemical and metabolic changes within the myocardium. Depletion of oxygen switches the aerobic cellular metabolism to anaerobic metabolism and impairs the oxidative phosphorylation pathway eventually leading to cardiomyocyte death. Several studies suggest an interlink between COVID-19 and ischemic heart disease. An increased ACE2 receptor expression in the myocardium may partly contribute to the myocardial injuries that are observed in patients affected by SARS-CoV-2. Furthermore, pre-existing cardiovascular disease, in conjunction with an aggravated inflammatory response which causes an up-regulation in pro-inflammatory cytokines. Moreover, patients with atherosclerosis are observed to be more prone to ischemic attacks when affected by COVID-19, due to hypercoagulation in the blood as well as elevated pro-inflammatory markers

Effect of temperature distribution and thermal gradient on the thermal response of steel-concrete composite girders

Thermal loads significantly influence bridge performance, particularly in extreme climates. This study identified a significant scope for investigating how changes in constituent material strength influence the overall temperature field and affect stress distribution in composite bridges. Also, this study focuses on investigating the thermal effects on steel-concrete composite bridges, an area that hasn't been extensively explored compared to concrete or steel bridges. The objective is to develop an efficient Finite Element (FE) model to simulate temperature variations and their impact on composite bridge girders considering varying concrete strengths. It involves developing an experimentally validated FE model of a dimensionally reduced steel-concrete composite bridge girder to assess the structural effects of a 24-hour simulated temperature field through a sequentially coupled thermo-mechanical analysis technique in Abaqus. The findings indicate that under similar thermal boundary conditions, composite bridge girder specimens with varying concrete strengths exhibit differences in stress values.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author

COVID-19 and Coronary Heart Disease

Coronary heart disease (CHD) is the leading cause of mortality worldwide. One of the main contributions of mortality and morbidity in CHD patients is acute myocardial infarction (AMI), which is the result of abrupt occlusion of an epicardial coronary artery due to a sudden rupture of atherosclerotic plaque, causing myocardial ischemia. In the initial stage of myocardial ischemia, lack of oxygen and nutrient supply results in biochemical and metabolic changes within the myocardium. Depletion of oxygen switches the aerobic cellular metabolism to anaerobic metabolism and impairs the oxidative phosphorylation pathway eventually leading to cardiomyocyte death. Several studies suggest an interlink between COVID-19 and ischemic heart disease. An increased ACE2 receptor expression in the myocardium may partly contribute to the myocardial injuries that are observed in patients affected by SARS-CoV-2. Furthermore, pre-existing cardiovascular disease, in conjunction with an aggravated inflammatory response which causes an up-regulation in pro-inflammatory cytokines. Moreover, patients with atherosclerosis are observed to be more prone to ischemic attacks when affected by COVID-19, due to hypercoagulation in the blood as well as elevated pro-inflammatory markers.</jats:p

Seismic performance evaluation of multi column bridge bent retrofitted with different alternatives

Highway bridges constitute a large portion of the national wealth and build up the foundation for economic development. Due to aging and deterioration, they require regular monitoring, evaluation and repair. More than 40% of Canadian bridges have crossed half of their anticipated service life. Many of these are structurally deficient and require major maintenance and rehabilitation. Although budget is allocated each year for maintenance and rehabilitation programme, the amount is usually small and covers only 30% to 70% of the actual maintenance needs. This fact raises the need for identifying bridges that require immediate attention where a significant portion of maintenance resources should be utilized. This study developed an integrated bridge prioritization index for a network of bridges to determine the prioritized work considering the importance of the bridge, cost associated with its rehabilitation and current condition. Once the bridge has been selected it is necessary to select proper retrofit techniques. In order to select a suitable retrofit technique this research has compared the performance of a pre-1965 designed multi column bridge bent retrofitted with different rehabilitation techniques, namely FRP jacketing, steel jacketing, concrete jacketing and Engineered Cementitious Composites (ECC) jacketing. The performance of the four different retrofitting strategies is compared in terms of base shear capacity demand ratio, ductility demand, residual drift and damage states obtained from nonlinear Incremental Dynamic Analysis (IDA) and static pushover analysis. Statistical comparisons of static (pushover) against dynamic analyses results have been performed in terms of performance criteria such as displacement and base shear at cracking, yielding and crushing. Moreover, this research assessed the fragility of this retrofitted multi column bridge bent under near fault and far field ground motions. The study aimed to capture the impact of different retrofit techniques on the vulnerability of a retrofitted bridge bent. Through rigorous analyses and applying multi-criteria decision making this study developed a decision making tool that will assist in identifying the most effective retrofitting scheme considering its performance under seismic hazards. The results showed that bridge bent retrofitted with ECC jacketing performed better and deemed to be the optimal retrofit alternative.Applied Science, Faculty ofEngineering, School of (Okanagan)Graduat