Individual polychlorinated biphenyl (CB) congeners in adipose and whole blood tissues of a capacitor manufacture worker (occupational/accidental exposure) and of the general population were determined. Nondestructive sample cleanup and multidimensional gas chromatography-electron capture detection (MDGC-ECD) techniques were applied. Special attention was given to the toxicologically relevant congeners CB-77, CB-126, CB-169, CB-105, CB-114, CB-118, CB-156, CB-167, and CB-189 (IUPAC). Lipid-based tissue contents of sigma CBs were higher in the occupationally/accidentally exposed worker (adipose = 7,000 ng/g; whole blood = 11 ng/g) than in the general population (adipose = 300 ng/g; whole blood = 1.9 ng/g). Among the non-ortho Cl CBs, CB-77 was below detection limit (< 1.0 pg/g). The contents of CB-126 for the capacitor manufacture worker were 2,000 and 3 pg/g, and in the general population were 100 and 2 pg/g for adipose and whole blood, respectively. The corresponding data for CB-169 were 3,500 and 4 for adipose and whole blood, respectively, in the exposed worker, and 40 and 2 for adipose and whole blood, respectively, in the general population. Congeners with highest contents were CB-153, CB-138, CB-180, CB-170, and CB-187. These congeners possess chlorine substitution patterns, making them resistant to metabolism. X/153 ratios suggest that both PB and 3-MC type cytochrome P-450 enzymes were induced in the exposed worker, as well as in the general population.
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http://dx.doi.org/10.1080/00039896.1994.9954990 | DOI Listing |
Background: Differences in patient characteristics across geographical regions may result in heterogeneity in clinical trial populations. evoke (NCT04777396) and evoke+ (NCT04777409) are two phase 3, multinational, randomised trials investigating semaglutide versus placebo in individuals with mild cognitive impairment or mild dementia due to Alzheimer's disease (AD) (early AD). We present baseline characteristics across the geographical regions in evoke/evoke+.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Biomedical Engineering, McGill University, Montreal, QC, Canada.
Background: Randomized placebo-controlled trials (RCTs) are the gold standard to evaluate efficacy of new drug treatments for Alzheimer's disease. For example, the United States FDA approved the brain amyloid-targeting drug lecanemab following CLARITY AD, Biogen and Eisai's Phase 3 RCT. However, recruiting enough participants for a high-powered and demographically representative trial is difficult and expensive.
View Article and Find Full Text PDFBackground: Understanding the fundamental differences between the human and pre-human brain is a prerequisite for designing meaningful models and therapies for AD. Expressed CHRFAM7A, a human restricted gene with carrier frequency of 75% in the human population predicts profound translational significance.
Method: The physiological role of CHRFAM7A in human brain is explored using multiomics approach on 600 post mortem human brain tissue samples (ROSMAP).
Background: There are no cures for Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by elevation of beta-amyloid and tau proteins besides neuronal death and causing cognitive impairment. Phosphodiesterase 5 (PDE5) is a cyclic guanosine monophosphate-degrading enzyme involved in numerous biological pathways including those relevant to memory formation. PDE5 inhibition offers the potential to attenuate AD progression by acting at the downstream level of beta-amyloid and tau elevation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Center for Health + Technology, University of Rochester Medical Center, Rochester, NY, USA.
Background: To bolster clinical trial infrastructure, there is a need to develop novel, valid, and reliable patient-reported outcome (PRO) measures capable of tracking clinically-relevant changes in Alzheimer's disease (AD), Mild Cognitive Impairment (MCI) and dementia over time. This research describes the development and validation of the Alzheimer's Disease-Health Index (AD-HI) as a tool to measure how patients feel and function in response to therapeutic intervention.
Method: We previously conducted semi-structured qualitative interviews and a national cross-sectional study with individuals with AD, MCI and dementia to ascertain the most prevalent and impactful symptoms identified by the participants.
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