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Summary: How does the brain encode courage in a real-life fearful situation that demands an immediate response? In this study, volunteers who fear snakes had to bring a live snake into close proximity with their heads while their brains were scanned using functional magnetic resonance imaging (fMRI). Bringing the snake closer was associated with a dissociation between subjective fear and somatic arousal. Activity in the subgenual anterior cingulate cortex (sgACC) and the right temporal pole was positively correlated with such action. Further, activity in the sgACC was positively correlated with the level of fear upon choosing to overcome fear but not upon succumbing to it. Conversely, activity in a set of interrelated temporal lobe structures, including the amygdala, was attenuated as the level of fear increased when choosing to overcome fear. We propose how the internally reinforced fast representational shift, in which the courageous-response representation gains control over behavior, takes place. Video Abstract: Display Omitted [Copyright &y& Elsevier]

[Display omitted] Dermal exposure to low volatility organophosphorus chemical warfare agents (OP CWA) poses a great risk to the exposed person. Due to their lipophilic nature, these compounds rapidly absorb into the skin, leading to the formation of a "dermal reservoir" from which they slowly enter the bloodstream causing prolonged intoxication. Traditionally, strategies to counter the toxicity of such substances consist of chemical decontamination/physical removal of the residual agent from the skin surface (preferably as soon as possible following the exposure) and administration of antidotes in the case of intoxication signs. Hence, these strategies are unable to counter a substantial amount of the agent, which accumulates inthe dermal reservoir. More than a decade ago, the concept of a "catch-up therapy" intended to neutralize the dermal reservoir was suggested. Herein, we describe examples of potential "catch-up therapy" lotions - vehicles designed to deliver small nucleophilic molecules into the skin and potentially decompose the remaining CWA before it reaches the blood stream. Eleven nucleophilic compounds, based on approved drugs, were initially screened. They were then tested in various binary solutions, for their detoxification efficacy and degradation ability towards lipophilic OP CWA models such as dibutylphosphofluoridate and o -nitro-phenyl diphenyl phosphate, as well as the nerve agent VX, by means of kinetic 31P NMR and UV–Vis spectroscopy. Of these, the potassium and diethyl ammonium salts of acetohydroxamic acid (AHAK and AHA DEA) in (DMSO/H 2 O 1:4) were found to be the most active nucleophiles, hydrolyzing VX in practical time scales (t 1/2 = 5.28 and 6.78 min, respectively). The vehicle solution DMSO/H 2 O 1:4 promoted the penetration of substantial amounts of AHA K and AHA DEA through excised pig skin in in-vitro studies, suggesting that such formulations may serve as useful CWA nucleophilic scavengers for both on and within -skin detoxification. These findings may pave the way to a more efficacious treatment against low volatility OP CWA percutaneous poisoning. [ABSTRACT FROM AUTHOR]

• Whole-body sarin exposure to a low concentration of 0.52 μg/L was sufficient in inducing pin-point pupils. • Whole-body sarin exposure leads to ocular surface histopathological lesions in a dose-response manner. • Topical 1 μg VX exposure induces a corneal histopathological damage while anti-muscarinic treatments alleviate this insult. Eye exposure to organophosphate (OP) chemical warfare irreversible acetylcholinesterase inhibitors, results in long-term miosis and impaired visual function. In contrast to the well-documented miotic and ciliary muscle spasm observed following chemical warfare, OP ocular exposure, little is known regarding the ocular surface histopathological insult. The aim of the present study was to determine the degree of the ocular surface insult following sarin or VX ocular exposure and to evaluate potential anti-cholinergic treatments in counteracting this insult. Rats that were whole body exposed to various sarin concentrations (0.049–43 μg/L; 5 min exposure), showed a dose-dependent miotic response and light reflex impairment. Following whole body sarin exposure, a dose dependent ocular surface histopathological insult was developed. A week following exposure to a low concentration of 0.05 μg/L, conjunctival pathology was observed, while corneal insult was noticed only following exposure to a concentration of 0.5 μg/L and above. Both tissues presented poorer outcomes when exposed to higher sarin concentrations. In contrast, eyes topically exposed to 1 μg sarin demonstrated no ocular insult a week following exposure. On the contrary, topical exposure to 1 μg VX resulted in a significant corneal insult. Anticholinergic treatments such as 0.1% atropine or 2% homatropine, given shortly following VX exposure, counteracted this insult. The results of this study show that not only do anti-cholinergic treatments counteract the miotic response, but also prevent the histopathological insult observed when given shortly following OP exposure. [ABSTRACT FROM AUTHOR]

The generation of adaptive immunity by vaccination is usually a prolonged process that requires multiple dosing over several months. Hence, vaccines are administered for disease prevention a relatively long time prior to possible infection as opposed to post-exposure prophylaxis, which typically requires rapid intervention such as antibiotic therapy. The emergence of pathogens resistant to common antibiotic treatments has prompted the search for alternative therapeutic strategies. We previously demonstrated that vaccination of mice with the F1 capsular antigen of Yersinia pestis elicits specific and effective yet, unexpectedly, rapid anti-plague immunity. Here, we show by applying genetic and immunological approaches that the F1 antigen is targeted by peritoneal innate-like B1b cells that generate a prompt T-independent (TI) anti-F1 humoral response. The rapid F1-mediated defense response was diminished in Xid (Btk m ) mice in which B1 cell numbers and activity are limited. Binding of fluorophore-labeled F1 to peritoneal B1b cells was detected as soon as 6 h post vaccination, emphasizing the high speed of this process. By assessing the ability to achieve rapid immunity with monomerized F1, we show that the natural polymeric structure of F1 is essential for (i) rapid association with peritoneal B1b cells, (ii) early induction of anti-F1 titers and (iii) rapid TI immunity in the mouse model of bubonic plague. These observations shed new light on the potential of novel as well as well-known protective antigens in generating rapid immunity and could be implemented in the rational design of future vaccines., Competing Interests: The authors declare no competing interests.