Hypoxia Due to Cardiac Arrest Induces a Time-Dependent Increase in Serum Amyloid β Levels in Humans

Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3–10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD

Corporate ethical identity as a determinant of firm performance : a test of the mediating role of stakeholder satisfaction

In this article, we empirically assess the impact of corporate ethical identity (CEI) on a firm’s financial performance. Drawing on formulations of normative and instrumental stakeholder theory, we argue that firms with a strong ethical identity achieve a greater degree of stakeholder satisfaction (SS), which, in turn, positively influences a firm’s financial performance. We analyze two dimensions of the CEI of firms: corporate revealed ethics and corporate applied ethics. Our results indicate that revealed ethics has informational worth and enhances shareholder value, whereas applied ethics has a positive impact through the improvement of SS. However, revealed ethics by itself (i.e. decoupled from ethical initiatives) is not sufficient to boost economic performance.Publicad

Features of Aβ42 elevation profiles were compared with 6-month overall cerebral outcome.

<p>(<b>A</b>) Magnitude of Aβ42 rise; (<b>B</b>) ratio of maximum to baseline Aβ42; (<b>C</b>) duration of major Aβ42 rise; (<b>D</b>) sum of <b>A</b> to <b>C</b> plus maximum slope of Aβ42 rise. Error bars are the standard error of the means.</p

Characteristics of serum Aβ42 elevation profiles from resuscitated survivors of cardiac arrest during the first 96–108 hours following admission to the intensive care unit.

<p>Parameters were sorted on the basis of good or poor 6-month outcome. Blood sampling was terminated early for patients 1, 16, 19 and 22 for medical reasons, and rise durations could not be estimated for these patients. The Aβ42 score equals the sum of magnitude of rise, duration of rise, rise ratio and max slope.</p

Serum Aβ42 following resuscitation from cardiac arrest.

<p>CPC scores depicted are after discharge from the ICU and 6 months later. Panels on left (<b>A–C</b>) are profiles from patients exhibiting good outcomes, panels on the right (<b>D–F</b>) are from patients with poor outcome. (<b>E</b>) Illustration of Aβ42 profile analysis. Baseline Aβ42 was defined as the mean of the two lowest values in the initial 12 hours. The time of initial elevation was defined as the intersection between the baseline Aβ42 and the line of maximum ascension of the major elevation peak. The duration of the Aβ42 increase was defined as the difference between time of initial elevation and time beyond which no significant further rise was observed. The magnitude and maximum slope of rise are also indicated. (<b>A</b>) Patient exhibiting smallest relative increase in Aβ42 among all patients. For confirmation, the sample set was re-assayed on a different day. (<b>D</b>) Patient with poor outcome exhibiting the largest relative increase from baseline. (<b>C</b> and <b>F</b>) Patients with similar baseline Aβ42 and poor cerebral outcome upon discharge from the ICU. Six months later, patient BE had recovered good cerebral function, while patient LP had not. Error bars: standard deviation of triplicate measurements.</p