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We fractionated frontal cortical grey matter from human Alzheimer's disease and control subjects into four biochemically defined pools that represent four distinct compartments: soluble/cytosolic, peripheral membrane/vesicular cargo, integral lipid/membranous pools and aggregated/insoluble debris. Most of the readily extractable amyloid-β remains associated with a lipid/membranous compartment. There is an exchange of amyloid-β between the biochemical pools that was lost for the amyloid-β42 species in Alzheimer's disease, consistent with the peptide being irreversibly trapped in extracellular deposits. The quantitative amyloid-β data, combined with magnetic resonance imaging volumetric analysis of the amount of cortical grey matter in brain, allowed us to estimate the total mass of amyloid-β in Alzheimer's disease (6.5 mg) and control (1.7 mg) brains. The threshold positron emission tomography standard uptake value ratio of 1.4 equates to 5.0 μg amyloid-β/g of grey matter and the mean Alzheimer's disease dementia standard uptake value ratio level of 2.3 equates to 11.20 μg amyloid-β/g of grey matter. It takes 19 years to accumulate amyloid from the threshold positron emission tomography standard uptake value ratio to the mean value observed for Alzheimer's disease dementia. This accumulation time window combined with the difference of 4.8 mg of amyloid-β between Alzheimer's disease and control brain allows for a first approximation of amyloid-β accumulation of 28 ng/h. This equates to an estimated 2-5% of the total amyloid-β production being deposited as insoluble plaques. Understanding these rates of amyloid-β accumulation allows for a more quantitative approach in targeting the failure of amyloid-β clearance in sporadic Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Summary Objectives Extended-spectrum beta-lactamase-expressing Gram-negative bacilli (ESBL-GNB) now commonly cause community-acquired infections, including urinary tract infections (UTI), and represent a challenge for practitioners in choosing empirical antibiotics. The aim of this study was to describe the epidemiology and clinical characteristics of UTIs/bacteriuria due to ESBL-GNB in Australia. Methods At a single-site tertiary referral hospital, 100 cases with UTIs/bacteriuria due to ESBL-GNB were matched to 100 cases where UTIs/bacteriuria were caused by organisms matching the ESBL bacterial species that had routine susceptibility to antibiotics. Potential risk factors for ESBL-GNB UTI/bacteriuria and differences in clinical outcomes were identified. Results Length of admission prior to positive sample (odds ratio (OR) 1.3, p = 0.03, per week), exposure to antibiotics (OR 5.7, p < 0.001), return from overseas travel (OR 6.5, p = 0.002), and nursing home residency (OR 4.2, p = 0.03) were identified as risk factors associated with ESBL-GNB UTI/bacteriuria in the multivariate analysis. In addition, ESBL-GNB-infected cases subsequently had a longer inpatient stay (median 6 vs. 2 days, p = 0.002) and were admitted to the intensive care unit more frequently (28/100 vs. 8/100, p < 0.001). Conclusions Our results emphasize the need for culture of a mid-stream urine specimen prior to commencing antibacterials, especially in patients with the risk factors identified herein associated with ESBL-GNB UTI/bacteriuria. [ABSTRACT FROM AUTHOR]