Acetaminophen, via its reactive metabolite N-acetyl-p-benzo-quinoneimine and transient receptor potential ankyrin-1 stimulation, causes neurogenic inflammation in the airways and other tissues in rodents

Acetaminophen [N-acetyl-p-aminophenol (APAP)] is the most common antipyretic/analgesic medicine worldwide. If APAP is overdosed, its metabolite, N-acetyl-p-benzo-quinoneimine (NAPQI), causes liver damage. However, epidemiological evidence has associated previous use of therapeutic APAP doses with the risk of chronic obstructive pulmonary disease (COPD) and asthma. The transient receptor potential ankyrin-1 (TRPA1) channel is expressed by peptidergic primary sensory neurons. Because NAPQI, like other TRPA1 activators, is an electrophilic molecule, we hypothesized that APAP, via NAPQI, stimulates TRPA1, thus causing airway neurogenic inflammation. NAPQI selectively excites human recombinant and native (neuroblastoma cells) TRPA1. TRPA1 activation by NAPQI releases proinflammatory neuropeptides (substance P and calcitonin gene-related peptide) from sensory nerve terminals in rodent airways, thereby causing neurogenic edema and neutrophilia. Single or repeated administration of therapeutic (15-60 mg/kg) APAP doses to mice produces detectable levels of NAPQI in the lung, and increases neutrophil numbers, myeloperoxidase activity, and cytokine and chemokine levels in the airways or skin. Inflammatory responses evoked by NAPQI and APAP are abated by TRPA1 antagonism or are absent in TRPA1-deficient mice. This novel pathway, distinguished from the tissue-damaging effect of NAPQI, may contribute to the risk of COPD and asthma associated with therapeutic APAP use.-Nassini, R., Materazzi, S., Andre, E., Sartiani, L., Aldini, G., Trevisani, M., Carnini, C., Massi, D., Pedretti, P., Carini, M., Cerbai, E., Preti, D., Villetti, G., Civelli, M., Trevisan, G., Azzari, C., Stokesberry, S., Sadofsky, L., McGarvey, L., Patacchini, R., Geppetti, P. Acetaminophen, via its reactive metabolite N-acetyl-p-benzo-quinoneimine and transient receptor potential ankyrin-1 stimulation causes neurogenic inflammation in the airways and other tissues in rodents. FASEB J. 24, 4904-4916 (2010). www.fasebj.org

Threshold In School – As Event And Place For The Autism Spectrum Disorder Pupil

As architects and designers we have a responsibility to provide an inclusive built environment. For the Autistic Spectrum Disorder (ASD) sufferer however, the built environment can be a frightening and confusing place, difficult to negotiate and tolerate. The challenge of integrating more fully into society is denied by an alienating built environment. This barrier can be magnified for ASD pupils in a poorly designed school, where their environment can further distance them from learning. Instead, if more at ease in their surroundings, in an ASD friendly environment, the ASD pupil stands a greater chance of doing better.

Whilst researchers have looked at the classroomenvironment, the transition of classroom to corridor andbeyond has so far been largely ignored. However, theneed for a well-considered threshold between class andcorridor needs to be considered. In this regard, threshold is much more than a doorway, but instead an event that demands a carefully considered place. The following paper firstly outlines why threshold as place andevent for the ASD pupil should be given consideration. It then goes onto highlight, through case studies in anIrish context, the opportunities for aiding the ASD pupil integrating in a mainstream school environment throughsensitive use of threshold. Finally it highlights inconclusion, some of the benefits for an enriched school environment for all pupils, if considering threshold as design generator.The objective is straightforward. By increasing awareness of the relationship between the ASD child and the built environment it will hopefully facilitate greater inclusion of the ASD pupil into mainstream education and society at large.

Conceptual and Perceptual Priming and Dissociation in Chronic Posttraumatic Stress Disorder.

Cognitive models of posttraumatic stress disorder (PTSD) assert that memory processes play a significant role in PTSD (see e.g., Ehlers & Clark, 2000). Intrusive reexperiencing in PTSD has been linked to perceptual processing of trauma-related material with a corresponding hypothesized lack of conceptual processing. In an experimental study that included clinical participants with and without PTSD (N = 50), perceptual priming and conceptual priming for trauma-related, general threat, and neutral words were investigated in a population with chronic trauma-induced complaints as a result of the Troubles in Northern Ireland. The study used a new version of the word-stem completion task (Michael, Ehlers, & Halligan, 2005) and a word-cue association task. It also assessed the role of dissociation in threat processing. Further evidence of enhanced perceptual priming in PTSD for trauma stimuli was found, along with evidence of lack of conceptual priming for such stimuli. Furthermore, this pattern of priming for trauma-related words was associated with PTSD severity, and state dissociation and PTSD group made significant contributions to predicting perceptual priming for trauma words. The findings shed light on the importance of state dissociation in trauma-related information processing and posttraumatic symptoms.

Increasing entanglement through engineered disorder in the random Ising chain

The ground-state entanglement entropy between block of sites in the random Ising chain is studied by means of the Von Neumann entropy. We show that in presence of strong correlations between the disordered couplings and local magnetic fields the entanglement increases and becomes larger than in the ordered case. The different behavior with respect to the uncorrelated disordered model is due to the drastic change of the ground state properties. The same result holds also for the random three-state quantum Potts model.

Metastable anions of dinitrobenzene: Resonances for electron attachment and kinetic energy release

Attachment of free, low-energy electrons to dinitrobenzene (DNB) in the gas phase leads to DNB as well as several fragment anions. DNB, (DNB-H), (DNB-NO), (DNB-2NO), and (DNB-NO2) are found to undergo metastable (unimolecular) dissociation. A rich pattern of resonances in the yield of these metastable reactions versus electron energy is observed; some resonances are highly isomer-specific. Most metastable reactions are accompanied by large average kinetic energy releases (KER) that range from 0.5 to 1.32 eV, typical of complex rearrangement reactions, but (1,3-DNB-H)(-) features a resonance with a KER of only 0.06 eV for loss of NO. (1,3-DNB-NO)(-) offers a rare example of a sequential metastable reaction, namely, loss of NO followed by loss of CO to yield C5H4O- with a large KER of 1.32 eV. The G4(MP2) method is applied to compute adiabatic electron affinities and reaction energies for several of the observed metastable channels. (C) 2010 American Institute of Physics. [doi:10.1063/1.3514931]

Regulatory regime change in Turkish banks:Reactive or proactive?

This paper examines the positive contributions made toward restructuring the regulatory framework of Turkey's banking and financial sectors prior to and post the 2000–2001 financial crisis. Drawing on a framework initially developed by Onis and Senses, 2007 and Onis and Senses, 2009 and further referred to by Onis, 2009 and Onis, 2010 it argues that financial reforms undertaken by the Turkish government would not have been successful without the strong support of domestic coalitions. While the external pressures put on the Turkish government from the International Monetary Fund, The World Bank and the European Union for financial reforms were necessary to kick start the reforms as a reactive process, these pressures on their own may have served only the interests of financial business elites at the expense of the broader stakeholders. Empirical data for the study was collected from documentary analysis of key financial institutions and interviews with twenty major Turkish regulatory agents and other stakeholders. The paper then discusses how the perceptions of these stakeholders are embodied into, and have influenced, regulatory regime change in Turkey from a reactive state to a more proactive one.

Working with the 'System' and 'Lifeworld': Using Action Research to Enhance Resilience and Attachment in a Children's Home

Residential child care workers in the UK are caught betwen competing imperatives on a grand scale. On the one hand, they are required to implement an increasing raft of policy. On the other, they must proactively engage with the young people under their care.