The Viral Hypothesis in Alzheimer's Disease: Novel Insights and Pathogen-Based Biomarkers.

Early diagnosis of Alzheimer's disease (AD) and the identification of significant risk factors are necessary to better understand disease progression, and to develop intervention-based therapies prior to significant neurodegeneration. There is thus a critical need to establish biomarkers which can predict the risk of developing AD before the onset of cognitive decline. A number of studies have indicated that exposure to various microbial pathogens can accelerate AD pathology.

Characterization of 3(3,4-dihydroxy-phenyl) propionic acid as a novel microbiome-derived epigenetic modifier in attenuation of immune inflammatory response in human monocytes.

Recent studies suggest that microbiome derived 3(3,4-dihydroxy-phenyl) propionic acid (DHCA) attenuates IL-6 cytokine production through downregulation of the epigenetic modifier DNA Methyltransferase 1 (DNMT1) expression and inhibition of DNA methylation at the 5'-C-phosphate-G-3' (CpG)-rich IL6 sequence introns 1 and 3 in a mouse model of depression. In this study, we extended the investigation of DHCA epigenetic mechanisms in IL-6 expression in human peripheral blood mononuclear cells (PBMC). Using Lucia Luciferase reporter gene system we identified CpG-rich sequences in which of methylation is influenced by DHCA similar to what observed in response to treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine.

Potential Novel Role of COVID-19 in Alzheimer's Disease and Preventative Mitigation Strategies.

There are a number of potential implications for the field of Alzheimer's disease (AD) stemming from the global spread of SARS-CoV-2. Neuroinflammation is known to be a prominent feature of neurodegeneration and plays a major role in AD pathology. Immune response and excessive inflammation in COVID-19 may also accelerate the progression of brain inflammatory neurodegeneration, and elderly individuals are more susceptible to severe outcomes after SARS-CoV-2 infection.

The dichotomous role of the gut microbiome in exacerbating and ameliorating neurodegenerative disorders.

Introduction: Age related neurodegenerative disorders affect millions of people around the world. The role of the gut microbiome (GM) in neurodegenerative disorders has been elucidated over the past few years. Dysbiosis of the gut microbiome ultimately results in neurodegeneration.

Myocardial Scar Detection by Standard CT Coronary Angiography.

We have described a myocardial infarct scar identified by a standard dual source CT coronary angiography (CTCA). We were able to detect the scar during the routine coronary assessment without contrast late enhancement and without additional radiation exposure. It is therefore feasible to assess chronic scar using a standard CTCA technique.

Prevalence of coronary artery calcium scores and silent myocardial ischaemia was similar in Indian Asians and European whites in a cross-sectional study of asymptomatic subjects from a U.K. population (LOLIPOP-IPC).

Background: Coronary heart disease (CHD) mortality is 70% higher among Indian Asians (IA) than European whites (EW), the reasons for this excess remain unexplained. Coronary artery calcification (CAC) is highly correlated with coronary plaque burden and silent myocardial ischaemia in EW; but fails to identify excess risk in IA. We hypothesised that IA have a higher prevalence of silent myocardial ischaemia compared to EW, despite similar CAC, and this may explain their excess CHD mortality.

Comparison between Tc-99m N-NOET and Tl-201 in the assessment of patients with known or suspected coronary artery disease.

Background: Technetium 99m N-ethoxy-N-ethyl dithiocarbamate (N-NOET) is a new radionuclide tracer for cardiac single photon emission computed tomography (SPECT) imaging. It combines the advantageous properties of a Tc-99m agent with the redistribution characteristics of thallium 201. We directly compared the two agents in patients with known or suspected coronary artery disease.

Prevalence of silent myocardial ischemia in asymptomatic individuals with subclinical atherosclerosis detected by electron beam tomography.

Background: Electron beam tomography coronary calcium imaging is an evolving technique for the early detection of coronary atherosclerosis, and recent studies have established its prognostic value in asymptomatic individuals. The relationship of coronary artery calcium scores (CAC) to obstructive coronary artery disease (CAD) has been poorly studied but is clinically relevant because it determines which individuals are likely to benefit from revascularization procedures. Hence, we prospectively evaluated the prevalence of myocardial ischemia in asymptomatic patients with cardiovascular risk factors and subclinical atherosclerosis.

Effects of carvedilol on left ventricular remodelling in chronic stable heart failure: a cardiovascular magnetic resonance study.

Background: The ability of beta blockers to improve left ventricular function has been demonstrated, but data on the effects on cardiac remodelling are limited.

Objective: To investigate, using cardiovascular magnetic resonance (CMR), the effects of carvedilol on left ventricular remodelling in patients with chronic stable heart failure and left ventricular systolic dysfunction caused by coronary artery disease.

Design: Randomised, double blind, placebo controlled study.

Rapid assessment of patients with non-ST-segment elevation acute chest pain: troponins, inflammatory markers, or perfusion imaging?

Background: Perfusion imaging during or soon after pain has been shown to provide diagnostic and prognostic information in patients with suspected angina. Measurement of troponin I (TnI) and troponin T (TnT) provides similar information but only several hours after onset of pain. The role of inflammatory markers in this setting is less clear.

Impact of revascularization and myocardial viability determined by nitrate-enhanced Tc-99m sestamibi and Tl-201 imaging on mortality and functional outcome in ischemic cardiomyopathy.

Background: Nitrate-enhanced perfusion imaging has been shown to detect viability in dysfunctional myocardium, but nitrate-enhanced technetium 99m sestamibi has not been compared with nitrate-enhanced thallium 201.

Methods And Results: Fifty-six patients with ischemic cardiomyopathy and heart failure (New York Heart Association classes II-IV) were scheduled for revascularization. Through use of a matching 12-segment model, nitrate-enhanced Tl-201 and Tc-99m sestamibi uptake at rest was assessed by 2 sets of blinded investigators.

Biodistribution, radiation dosimetry and pharmacokinetics of 111In-antimyosin in idiopathic inflammatory myopathies.

Unlabelled: In view of the established role of 111In-antimyosin in the detection of heart muscle pathology, radiation dose estimates were made for this substance. Biodistribution and biokinetic data were obtained from our studies, which failed to show abnormal uptake of 111In-antimyosin in localized sites of skeletal muscle involvement in patients with idiopathic inflammatory myopathies.

Methods: After intravenous administration of 74 MBq (2 mCi) 111In-antimyosin, gamma camera scintigraphy was performed in 12 adult patients with inflammatory muscle disease and in 2 control patients.

Influence of background correction in the estimation of myocardial uptake of 99mTc labelled perfusion imaging agents.

The effects of different corrections for background activity in the estimation of low organ uptake of radiopharmaceuticals have been examined using myocardial perfusion imaging agents. Estimates of myocardial uptake of 99mTc-labelled MIBI and tetrofosmin were made both at rest and after exercise. Patients were given one or other of the agents (12 MIBI; 17 tetrofosmin) and the measurements at rest and after exercise were made within a week of each other using a planar gamma camera method incorporating an attenuation-corrected, geometric mean technique.

Superiority of nitrate-enhanced 201Tl over conventional redistribution 201Tl imaging for prognostic evaluation after myocardial infarction and thrombolysis.

Background: 201Tl imaging has been widely used for postinfarction risk stratification. However, thrombolytic therapy and aspirin have significantly changed outcome, and there are few nuclear imaging studies that assess prognosis in such patients. Furthermore, newer techniques of 201Tl imaging, such as reinjection and nitrate-enhanced rest 201Tl imaging, have been shown to improve the detection of viable but jeopardized myocardium.

The effect of training on the interpretation of 99Tcm-sestamibi myocardial perfusion SPET in patients with suspected coronary artery disease.

The aim of this study was to examine the effect of a period of concentrated training in nuclear cardiology on the accuracy of reporting 99Tcm-sestamibi (99Tcm-MIBI) single photon emission tomographic (SPET) images. Two visiting cardiologists, with no previous experience in nuclear cardiology, were asked to report blindly 60 99Tcm-MIBI SPET scans after 2 weeks of training in nuclear cardiology. One (observer 2) reported the same scans blindly after 2 months of further training.

Detection of coronary artery disease with myocardial contrast echocardiography: comparison with 99mTc-sestamibi single-photon emission computed tomography.

Background: The purpose of this study was to determine whether myocardial contrast echocardiography (MCE) can be used to detect coronary artery disease (CAD) during rest and pharmacological stress in humans through the use of venous injections of contrast.

Methods And Results: Thirty patients with known or suspected CAD underwent MCE and 99mTc-sestamibi single-photon emission computed tomography (SPECT) at baseline and after dipyridamole (0.56 mg x kg(-1)) infusion.

Beneficial effects of intravenous and oral carvedilol treatment in acute myocardial infarction. A placebo-controlled, randomized trial.

Background: Evidence of efficacy and safety of beta-blockers after thrombolysis for acute myocardial infarction (AMI) is equivocal. Newer beta-blockers such as carvedilol have not been tested in this setting.

Methods And Results: This study investigated the effects of acute (intravenous) and long-term (6 months, oral) treatment with carvedilol versus placebo in 151 consecutive patients with AMI.

Prognostic value of stress dobutamine technetium-99m sestamibi single-photon emission computed tomography (SPECT) in patients with suspected coronary artery disease.

Inotropic stress using graded dobutamine infusion has evolved as an alternative form of pharmacologic stress in conjunction with perfusion and functional imaging for evaluation of coronary heart disease. However, the prognostic value of technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) imaging in patients undergoing dobutamine stress testing for the detection of coronary artery disease is unclear. Accordingly, 61 patients undergoing coronary arteriography for the evaluation of chest pain on the basis of symptoms and treadmill exercise electrocardiography underwent SPECT imaging at rest and during stress.

Prognostic value of predischarge exercise testing, ejection fraction, and ventricular ectopic activity in acute myocardial infarction treated with streptokinase.

The relative importance of prognostic parameters that delineate left ventricular function, myocardial ischemia, and arrhythmogenic potential after thrombolytic therapy is not clear. This study investigated 112 patients with acute myocardial infarction who were treated with thrombolysis to determine the relative prognostic value of predischarge treadmill exercise testing, radionuclide ventriculography, and ambulatory electrocardiographic monitoring for ventricular ectopic activity. During a mean follow-up period of 18 months (range 6 to 30), 42 first cardiac events were recorded, consisting of 3 deaths, 6 reinfarctions, 16 bouts of unstable angina, 16 episodes of heart failure, and 1 arrhythmic event.

Technetium 99m-labeled sestamibi imaging reliably identifies retained contractile reserve in dyssynergic myocardial segments.

Background: Recently there has been considerable controversy regarding the use of 99mTc-labeled sestamibi as an agent for the detection of viable myocardium. In this study we have used dobutamine-induced left ventricular wall thickening by echocardiography in regions with evidence of resting dyssynergy of the left ventricle as an indicator of retained contractile reserve and compared this with 99m Tc-labeled sestamibi uptake in the same regions.

Methods And Results: Twenty-seven patients with documented coronary artery disease and severe regional wall motion abnormalities underwent low-dose (5 to 15 micrograms/kg/min) dobutamine echocardiography and maximal (15 to 40 micrograms/kg/min) stress dobutamine 99mTc-labeled sestamibi single-photon emission computed tomographic imaging.