Background
It is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of ...regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation.
Methods
In a small animal model, synchrotron imaging was used to measure lung aeration and regional‐specific ventilation (sV̇). Heterogeneity of ventilation was calculated as the coefficient of variation in sV̇ (CVsV̇). The coefficient of variation in lung densities (CVD) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end‐expiratory pressure (ZEEP) and FIO2 0.21; ZEEP and FIO2 1.0; PEEP 12 cmH2O and FIO21.0 (Open Lung‐PEEP = OLP).
Results
The mean tissue density at OLP was lower than ZEEP‐1.0 and ZEEP‐0.21. There were larger subregions with low sV̇ and poor aeration at ZEEP‐0.21 than at OLP: 12.9 ± 9.0 vs. 0.6 ± 0.4% in the non‐dependent level, and 17.5 ± 8.2 vs. 0.4 ± 0.1% in the dependent one (P = 0.041). The CVsV̇ of the total imaged lung at PEEP 12 cmH2O was significantly lower than on ZEEP, regardless of FIO2, indicating more heterogeneity of ventilation during ZEEP (0.23 ± 0.03 vs. 0.54 ± 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP.
Conclusion
ZEEP together with low FIO2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions.
Mounting evidence suggests copper may influence the progression of Alzheimer's disease by reducing clearance of the amyloid beta protein (Abeta) from the brain. Previous experiments show that ...addition of only 0.12 PPM copper (one-tenth the Environmental Protection Agency Human consumption limits) to distilled water was sufficient to precipitate the accumulation of Abeta in the brains of cholesterol-fed rabbits (1). Here we report that addition of copper to the drinking water of spontaneously hypercholesterolemic Watanabe rabbits, cholesterol-fed beagles and rabbits, PS1/APP transgenic mice produced significantly enhanced brain levels of Abeta. In contrast to the effects of copper, we found that aluminum- or zinc-ion-supplemented distilled water did not have a significant effect on brain Ab accumulation in cholesterol-fed rabbits. We also report that administration of distilled water produced a reduction in the expected accumulation of Ab in three separate animal models. Collectively, these data suggest that water quality may have a significant influence on disease progression and Ab neuropathology in AD.
John Lennon's singing "you can count me out ... in" on the Beatles' White Album track "Revolution 1" seems like an embarrassing attempt to placate different audiences. But, in historical perspective, ...the 28-year-old pop star's uncertainty about his degree of engagement was perfectly congruent with the increasingly introverted direction of his songwriting, the evolution of the Beatles' relationship with their audiences, the skeptical stance of his musical peers, and the honest dilemmas of left-of-center movement politics in 1968.
Disease-modifying therapies are being developed for Alzheimer's disease (AD). These are expected to slow the clinical progression of the disease or delay its onset. Cerebral accumulation of amyloid ...beta (A beta) peptides is an early and perhaps necessary event for establishing AD pathology. Consequently therapies aimed at attenuating brain amyloidosis are expected to be disease modifying. Based on the epidemiological evidence pointing to a link between cholesterol metabolism and AD and the numerous laboratory studies implicating cholesterol in the process of A beta production and accumulation, it is now believed that cholesterol-lowering therapies will be of value as disease modifying agents. Several epidemiological studies revealed that statin use for the treatment of coronary arterial disease is associated with a decreased prevalence or a decreased risk of developing AD. These observations require both preclinical and clinical validation. The former involves testing statins in one or more animal models of AD in order to establish which disease features are affected by statin treatment, the relative efficacy with which different statins modify these features and the mechanism(s) by which statins affect AD phenotypes. The latter requires prospective, randomized, placebo controlled trials to evaluate the effect of statin treatment on cognitive and AD biomarker outcomes. We have initiated a study aimed at determining the effects of atorvastatin (Lipitor), a statin with the largest US market share, on brain A beta deposition in the PSAPP transgenic mouse model of Alzheimer's amyloidosis. Our results indicate that Lipitor treatment markedly attenuates A beta deposition in this animal model.
DeRosa draws on the records of the army and the Department of Defense's information offices, the content of the indoctrination materials themselves, and soldiers' recollections in analyzing the ...political messages the nation conveyed to its army during three decades of conscription. He examines how the program took root as an army institution, how its technique evolved over time, and how it interacted with the larger American political culture. In so doing, he explores the implications of trying to impose a political consensus on the army of a democracy.
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