The effect of regional ischemia on canine myocardial in situ free radical species was studied by the EPR method. Rapid fixation of heart muscle samples by freezeclamping was performed at the following physiological states: native myocardial blood circulation, regional ischemia with the presence of collateral circulation, total ischemia, and postischemic reperfusion. EPR spectra of the samples at -40 degrees C exhibited two free radical signals from the semireduced forms of ubiquinone and flavine coenzymes. Upon transition from normal blood supply to regional ischemia, an increase in the contribution of the flavine signal was registered, but reperfusion resulted in the recovery of the characteristics of EPR signals. It was found that the increase in the intensity of collateral circulation in the ischemic area led to an increase in the portion of ubisemiquinone in the integral EPR signal, whereas in total ischemia this signal was not registered. It was shown that the changes in spectral characteristics of integral free radical signals are accompanied by changes in their relaxation parameters.
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Alzheimers Dement
December 2024
Douglas Mental Health University Institute, Montreal, QC, Canada.
White matter hyperintensities (WMHs) are frequently observed in ageing individuals, and have a higher prevalence in neurodegenerative disorders such as Alzheimer's disease. Ex-vivo assessments of the microstructural alterations within WMHs have reported heterogeneous tissue alterations, with demyelination, axonal loss, and inflammation presenting with various degrees of severity. There is a crucial need to better assess the severity of WMH microstructural alterations in vivo, in particular with the emergence of anti-amyloid immunotherapies and the associated risk of Amyloid Related Imaging Abnormalities (ARIAs) in individuals with comorbid vascular disease.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Background: Vascular pathology associated with small vessel disease (SVD), such as microinfarcts and microbleeds, are common in elderly populations and significant contributors to cognitive impairment and dementia. Autosomal dominant cerebral arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL), caused by mutations in the Notch3 gene, is the most prominent inheritable SVD, with a common etiology of subcortical strokes and dementia. This study aimed to investigate additive or synergistic effects of CADASIL-related vascular alterations and familial Alzheimer's disease (FAD)-related amyloid pathology on cerebral metabolism of glucose and disease progression in a novel FAD-CADASIL mouse model.
View Article and Find Full Text PDFBackground: CADASIL, linked to NOTCH3 variants, is a primary monogenic cause of vascular dementia, leading to vascular cognitive impairment and dementia (VCID) observable in early stages. The NIH-funded USA CADASIL Consortium aims to explore CADASIL's onset and progression in the USA, crucial due to varying phenotype-genotype associations globally. The consortium will identify biological and clinical markers across the disease spectrum, contributing to clinical trial preparations.
View Article and Find Full Text PDFAim: To identify predictors and construct a model for predicting left ventricular (LV) ejection fraction (EF) in patients with ST-segment elevation myocardial infarction (STEMI).
Material And Methods: This was a prospective registry study of patients with STEMI admitted within the first 24 hours of the disease onset. Patients were evaluated and treated according to the current clinical guidelines.
Alzheimers Dement
December 2024
University of California, Davis, Sacramento, CA, USA.
Background: Microinfarcts, characteristic lesions of vascular dementia (VaD), are heterogenous and vary in appearance, which pose a considerable challenge for VaD grading as there is great interrater variability in microinfarct assessment. We propose a novel application of machine learning (ML) in the automated screening of microinfarcts, addressing a gap in the post-mortem analysis of VaD in whole slide images (WSIs) from human brain.
Method: Our study adapts a patch-based pipeline with convolutional neural networks (CNNs) to automate microinfarct screening in WSIs.
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