Impaired neuromuscular function by conjoint actions of organophosphorus insecticide metabolites omethoate and cyclohexanol with implications for treatment of respiratory failure, Clinical Toxicology,

Network hyperexcitability is a feature of Alzheimer’ disease (AD) as well as numerous transgenic mouse models of AD. While hyperexcitability in AD patients and AD animal models share certain features, the mechanistic overlap remains to be established. We aimed to identify features of network hyperexcitability in AD models that can be related to epileptiform activity signatures in AD patients. We studied network hyperexcitability in mice expressing amyloid precursor protein (APP) with mutations that cause familial AD, and compared a transgenic model that overexpresses human APP (hAPP) (J20), to a knock-in model expressing APP at physiological levels (APPNL/F). We recorded continuous long-term electrocorticogram (ECoG) activity from mice, and studied modulation by circadian cycle, behavioral, and brain state. We report that while J20s exhibit frequent interictal spikes (IISs), APPNL/F mice do not. In J20 mice, IISs were most prevalent during daylight hours and the circadian modulation was associated with sleep. Further analysis of brain state revealed that IIS in J20s are associated with features of rapid eye movement (REM) sleep. We found no evidence of cholinergic changes that may contribute to IIS-circadian coupling in J20s. In contrast to J20s, intracranial recordings capturing IIS in AD patients demonstrated frequent IIS in non-REM (NREM) sleep. The salient differences in sleep-stage coupling of IIS in APP overexpressing mice and AD patients suggests that different mechanisms may underlie network hyperexcitability in mice and humans. We posit that sleep-stage coupling of IIS should be an important consideration in identifying mouse AD models that most closely recapitulate network hyperexcitability in human AD.

PurposeThe purpose of this paper is to answer two research questions: How does a self-initiated migrant (SiM)'s talent identity work operate in relation to their culture, the societies in which they live, their interpersonal relationships and their tacit knowledge development? and how can global talent management be re-imagined in light of this?Design/methodology/approachThis co-constructed autoethnography is produced from reflexive, dyadic interviews and text “conversations” with an SiM doing “global talent identity work” and uses narrative analysis to investigate how liminal competence is developed across the life cycle.FindingsThis study shows how talent identity work is rooted in the lived, meaningful experiences of individual talent, from childhood to adult life in a pandemic. The authors add to knowledge about COVID-19 experiences of SiMs, uncover poignant examples of the role of migrant ethnic and knowledge discrimination and identify lessons for managerial practice in engendering liminality competence by combining global talent management and knowledge management.Practical implicationsLessons are drawn for global talent management strategies that appreciate and support individual talent ethnic and knowledge inclusion of underappreciated migrant talent.Originality/valueExamining the connection between talent identity work and liminality competence, the authors show how an individual's talent might be wasted through different forms of discrimination and highlight how ethnic discrimination during a pandemic points the way to positive changes in talent knowledge management initiatives. This study suggests ways in which ethnic and knowledge discrimination might be addressed through talent management strategies.

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Orexin A and B (hypocretin 1 and 2) are novel hypothalamic peptides and two receptor subtypes, OX 1 R and OX 2 R, were identified. Orexins are implicated in hyperphagia, arousal, and neuroendocrine and autonomic regulations. Recently, orexins were found to be antinociceptive supraspinally and spinally but sympathetically stimulating. This review summarizes the analgesic effects of orexins reported in acute, inflammatory, and neuropathic pain animal models. The antinociceptive effects of orexins are mediated by OX 1 R, but not opioid receptors. Purinergic P 2X and glycine receptors are supported to be involved in the intrathecal orexin-induced antiallodynia. Endogenous orexins may play a protective role after nociceptive stimulation.A novel family of hypothalamic peptides was identified by de Lecea et al. 1 and named as hypocretins for their structural homology to the gut hormone, secretin. Two peptides, hypocretin 1 and hypocretin 2, derived from a common precursor, prepro-hypocretin, were identified. 1 Six weeks later, Sakurai et al. 2 isolated the same hypothalamic neuropeptides in an independent study that searched for the effective ligands from brain extract acting at a panel of orphan G-protein-coupled receptors. These two peptides were named orexin A and orexin B for their orexigenic (appetite-stimulating) activity when given intracerebroventricularly (i.c.v.). Orexin A and orexin B, consisting of 33 and 28 amino acids, respectively, were matched with hypocretin 1 and hypocretin 2. 3