International journal of clinical and experimental medicine最新文献

[This retracts the article on p. 13127 in vol. 8, PMID: 26550235.].

Alzheimer's disease (AD) is a progressive, and often fatal, brain disease that causes neurodegeneration, resulting in memory loss as well as other cognitive and behavioral problems. Here, we propose a novel multimodal method combining independent components from MRI measures and clinical assessments to distinguish Alzheimer's patients or mild cognitive impairment (MCI) subjects from healthy elderly controls. 70 AD subjects (mean age: 77.15 ± 6.2 years), 98 MCI subjects (mean age: 76.91 ± 5.7 years), and 150 HC subjects (mean age: 75.69 ± 3.8 years) were analyzed. Our method includes the following steps: pre-processing, estimating the number of independent components from the MR image data, extracting effective voxels for classification, and classification using a support vector machine (SVM)-based classifier. As a result, with regards to classifying AD from healthy controls, we achieved a classification accuracy of 97.7%, sensitivity of 99.2%, and specificity of 96.7%; for differentiating MCI from healthy controls, we achieved a classification accuracy of 87.8%, a sensitivity of 86.0%, and a specificity of 89.6; these results are better than those obtained with clinical measurements alone (accuracy of 79.5%, sensitivity of 74.0%, and specificity of 85.1%). We found that (1) both AD patients and MCI subjects showed brain tissue loss, but the volumes of gray matter loss in MCI subjects was far less, supporting the notion that MCI is a prodromal stage of AD; and (2) combining gray matter features from MRI and three commonly used measures of mental status, cognitive function improved classification accuracy, sensitivity, and specificity compared with classification using only independent components or clinical measurements.

[This retracts the article on p. 7569 in vol. 8, PMID: 26221301.].

[This retracts the article on p. 17634 in vol. 8, PMID: 26770353.].

[This retracts the article on p. 4809 in vol. 7, PMID: 25663977.].

[This retracts the article on p. 5470 in vol. 8, PMID: 26131125.].

[This retracts the article on p. 13235 in vol. 8, PMID: 26550248.].

The cellular environment of the mammalian heart constantly is challenged with environmental and intrinsic pathological insults, which affect the proper folding of proteins in heart failure. The effects of damaged or misfolded proteins on the cell can be profound and result in a process termed "proteotoxicity". While proteotoxicity is best known for its role in mediating the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, its role in human heart failure also has been recognized. The UPR involves three branches, including PERK, ATF6, and IRE1. In the presence of a misfolded protein, the GRP78 molecular chaperone that normally interacts with the receptors PERK, ATF6, and IRE-1 in the endoplasmic reticulum detaches to attempt to stabilize the protein. Mouse models of cardiac hypertrophy, ischemia, and heart failure demonstrate increases in activity of all three branches after removing GRP78 from these internal receptors. Recent studies have linked elevated PERK and CHOP in vitro with regulation of ion channels linked with human systolic heart failure. With this in mind, we specifically investigated ventricular myocardium from 10 patients with a history of conduction system defects or arrhythmias for expression of UPR and autophagy genes compared to myocardium from non-failing controls. We identified elevated Chop, Atf3, and Grp78 mRNA, along with XBP-1-regulated Cebpa mRNA, indicative of activation of the UPR in human heart failure with arrhythmias.

[This retracts the article on p. 2662 in vol. 8, PMID: 25932216.].