Publications by authors named "Joshua T Chai"

Article Synopsis
  • Study investigates how high blood sugar (hyperglycemia) affects immune cells (macrophages) in diabetes, leading to an increased risk of cardiovascular disease.
  • Experiments using macrophages from diabetic mice showed they become "trained" to exhibit inflammatory behaviors even when glucose levels are normal, suggesting a lasting impact from prior high glucose exposure.
  • Bone marrow transplants from diabetic mice into healthy mice showed that this training can contribute to more severe artery disease, indicating that changes in immune cell behavior due to diabetes can promote ongoing cardiovascular issues.
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Background: Eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome) is a rare autoimmune condition characterized by inflammation of small- and medium-sized blood vessels, which usually presents with systemic vasculitis preceded by airway allergic hypersensitivity.

Case Summary: Here, we report a highly unusual case of acute ST-elevation myocardial infarction in a young and fit man with no cardiovascular risk factors. His emergency coronary angiography revealed disproportionately severe widespread coronary artery disease.

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Objective- Plaque macrophages are intricately involved in atherogenesis and plaque destabilization. We sought to identify functional pathways in human plaque macrophages that are differentially regulated in respect of (1) plaque stability and (2) lipid content. We hypothesized that differentially regulated macrophage gene sets would relate to genome-wide association study variants associated with risk of acute complications of atherosclerosis.

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Background & Aims: A recently-validated, highly-sensitive T2 mapping magnetic resonance (MRI) technique accurately quantifies carotid plaque lipid. The aims of this study were to determine: (i) the extent of carotid plaque lipid in patients with acute coronary syndromes (ACS); (ii) the effects of initiation of high-intensity statin on plaque lipid content and (iii) whether plaque lipid content is related to standard or 'functional' blood lipid measurements.

Methods: Statin naïve subjects presenting with ACS underwent carotid artery MRI at 3 T scanner to quantify plaque lipid.

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Background And Purpose: Techniques to stratify subgroups of patients with asymptomatic carotid artery disease are urgently needed to guide decisions on optimal treatment. Reliance on estimates of % luminal stenosis has not been effective, perhaps because that approach entirely disregards potentially important information on the pathological process in the wall of the artery.

Methods: Since plaque lipid is a key determinant of plaque behaviour we used a newly validated, high-sensitivity T2-mapping MR technique for a systematic survey of the quantity and distribution of plaque lipid in patients undergoing endarterectomy.

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Inflammatory processes are firmly established as central to the development and complications of cardiovascular diseases. Elevated levels of inflammatory markers have been shown to be predictive of future cardiovascular events. The specific targeting of these processes in experimental models has been shown to attenuate myocardial and arterial injury, reduce disease progression, and promote healing.

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Statins have been effective in reducing adverse cardiovascular events. Their benefits have been proportional to the level of plasma LDL-cholesterol reduction and seem to extend to patients with 'normal' levels of cholesterol at outset. Statins are also inexpensive and have a favourable side-effect profile.

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Objectives: The aim of this study was to: 1) provide tissue validation of quantitative T mapping to measure plaque lipid content; and 2) investigate whether this technique could discern differences in plaque characteristics between symptom-related and non-symptom-related carotid plaques.

Background: Noninvasive plaque lipid quantification is appealing both for stratification in treatment selection and as a possible predictor of future plaque rupture. However, current cardiovascular magnetic resonance (CMR) methods are insensitive, require a coalesced mass of lipid core, and rely on multicontrast acquisition with contrast media and extensive post-processing.

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Aims: Monocytes play critical roles in tissue injury and repair following acute myocardial infarction (AMI). Specifically targeting inflammatory monocytes in experimental models leads to reduced infarct size and improved healing. However, data from humans are sparse, and it remains unclear whether monocytes play an equally important role in humans.

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Purpose: To prospectively compare the black-blood ( BB black blood ) imaging efficiency of a delay alternating with nutation for tailored excitation ( DANTE delay alternating with nutation for tailored excitation ) preparation module with conventional double inversion-recovery ( DIR double inversion recovery ) and motion-sensitive driven equilibrium ( MSDE motion-sensitive driven equilibrium ) preparation modules and to introduce a new three-dimensional ( 3D three-dimensional ) T1-weighted magnetic resonance (MR) imaging sequence.

Materials And Methods: Carotid artery wall imaging was performed in 10 healthy volunteers and 15 patients in accordance with an institutional review board-approved protocol. Two-dimensional ( 2D two-dimensional ) turbo spin-echo ( TSE turbo spin echo ) and 3D three-dimensional fast low-angle shot ( FLASH fast low-angle shot ) sequences served as readout modules.

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Cardiovascular disease (CVD) remains the largest healthcare burden in the Western world; and the increasing prevalence of type II diabetes mellitus, at least partially driven by a trend in lifestyle changes associated with global economic development, is likely to fuel this CVD burden worldwide. Over the past two decades, there has been an increased awareness of the convergence of risk factors contributing to both cardiovascular disease and diabetes leading to the concept of the metabolic syndrome, and the realisation of the opportunity to intervene at this intersection to simultaneously target CVD and metabolic dysfunction. This brings together the fields of cardiovascular medicine, diabetology, and increasingly clinical immunology for a unified and concerted effort to reduce risk for both conditions simultaneously.

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Background: Atherosclerotic plaques in carotid arteries can be characterized in-vivo by multicontrast cardiovascular magnetic resonance (CMR), which has been thoroughly validated with histology. However, the non-quantitative nature of multicontrast CMR and the need for extensive post-acquisition interpretation limit the widespread clinical application of in-vivo CMR plaque characterization. Quantitative T2 mapping is a promising alternative since it can provide absolute physical measurements of plaque components that can be standardized among different CMR systems and widely adopted in multi-centre studies.

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Nicotinic acid (NA) regresses atherosclerosis in human imaging studies and reduces atherosclerosis in mice, mediated by myeloid cells, independent of lipoproteins. Since GPR109A is expressed by human monocytes, we hypothesized that NA may drive cholesterol efflux from foam cells. In THP-1 cells NA suppressed LPS-induced mRNA transcription of MCP-1 by 76.

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GPR109A has generated expanding interest since its discovery as the receptor for niacin a decade ago, along with deorphanisation as the receptor for endogenous ligand 3-hydroxy-butyrate shortly after. This interest is generated especially because of the continuing exploration of niacin's "pleiotropic" mechanisms of action and its potential in the "cross-talk" between metabolic and inflammatory pathways. As GPR109A's primary pharmacological ligand in clinical use, niacin has been used for over 50 years in the treatment of cardiovascular disease, mainly due to its favourable effects on plasma lipoproteins.

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A 63-year-old previously healthy woman developed a severe systemic infection 5 days after returning from a holiday to Southern Portugal. She subsequently died, and polymerase chain reaction of a blood sample was positive for Rickettsia conorii ssp israeliensis. The prevalence of severe forms of this illness in the Mediterranean Basin is discussed.

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We investigated sequence alternation, promoter methylation, and loss of heterozygosity (LOH) of the RB1 gene as possible mechanisms of its inactivation in retinoblastoma. In 42 Chinese patients with sporadic retinoblastoma, the promoter and entire coding region of RB1 were examined for sequence changes. Status of methylation of the CpG-rich island at the 5'end was determined by methylation specific PCR assay.

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