Nerve Agent

Over the past fifty years, swine models have been used for organophosphorus intoxication studies. Among these studies and others on the swine model in general, some physiological data, especially cholinesterase activity highly impacted by organophosphorus compounds like nerve agent VX, still need to be completed. To support and compare our model to others, we have published the experimental protocol, the physiological values of 31 juvenile anesthetized pigs, and the 6h-follow-up of six supplementary anesthetized control animals and 7 VX-intoxicated pigs...

Speech impediments are a prominent yet understudied symptom of Parkinson's disease (PD). While the subthalamic nucleus (STN) is an established clinical target for treating motor symptoms, these interventions can lead to further worsening of speech. The interplay between dopaminergic medication, STN circuitry, and their downstream effects on speech in PD is not yet fully understood. Here, we investigate the effect of dopaminergic medication on STN circuitry and probe its association with speech and cognitive functions in PD patients...

A-234 (ethyl N -[1-(diethylamino)ethylidene]phosphoramidofluoridate) is one of the highly toxic Novichok nerve agents, and its efficient degradation is of significant importance. The possible degradation mechanisms of A-234 by H2 O, H2 O2 , NH3 , and their combinations have been extensively investigated by using density functional theory (DFT) calculations. According to the initial intermolecular interaction and the proton transfer patterns between the detergent and the substrate A-234, the A-234 degradation reaction is classified into three categories, denoted as A, B, and C...

Alzheimer's disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia. Growing evidence suggests that Alzheimer's disease is associated with accumulating various amyloid-β oligomers in the brain, influenced by complex genetic and environmental factors. The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer's disease are believed to primarily result from synaptic dysfunction. Throughout life, environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders...

Rare neurological diseases, while individually are rare, collectively impact millions globally, leading to diverse and often severe neurological symptoms. Often attributed to genetic mutations that disrupt protein function or structure, understanding their genetic basis is crucial for accurate diagnosis and targeted therapies. To investigate the underlying pathogenesis of these conditions, researchers often use non-mammalian model organisms, such as Drosophila (fruit flies), which is valued for their genetic manipulability, cost-efficiency, and preservation of genes and biological functions across evolutionary time...

Intravenous (IV) medication administration error remains a major concern during the perioperative period. This review examines inadvertent IV anaesthesia induction agent administration via high-risk routes. Using Medline and Google Scholar, the author searched published reports of inadvertent administration via neuraxial (intrathecal, epidural), peripheral nerve or plexus or intracerebroventricular (ICV) route. The author applied the Human Factors Analysis and Classification System (HFACS) framework to identify systemic and human factors...

Nerve agents pose significant threats to civilian and military populations. The reactivation of acetylcholinesterase (AChE) is critical in treating acute poisoning, but there is still lacking broad-spectrum reactivators, which presents a big challenge. Therefore, insights gained from the reactivation kinetic analysis and molecular docking are essential for understanding the behavior of reactivators towards intoxicated AChE. In this research, we present a systematic determination of the reactivation kinetics of three V agents-inhibited four human ChEs [(AChE and butyrylcholinesterase (BChE)) from either native or recombinant resources, namely, red blood cell (RBC) AChE, rhAChE, hBChE, rhBChE) reactivated by five standard oximes...

Homeostasis is a self-regulatory process, wherein an organism maintains a specific internal physiological state. Homeostatic reinforcement learning (RL) is a framework recently proposed in computational neuroscience to explain animal behavior. Homeostatic RL organizes the behaviors of autonomous embodied agents according to the demands of the internal dynamics of their bodies, coupled with the external environment. Thus, it provides a basis for real-world autonomous agents, such as robots, to continually acquire and learn integrated behaviors for survival...

The re-bridging of the deficient nerve is the main problem to be solved after the functional impairment of the peripheral nerve. In this study, a directionally aligned polycaprolactone/triiron tetraoxide (PCL/Fe3 O4 ) fiber scaffolds were firstly prepared by electrospinning technique, and further then grafted with IKVAV peptide for regulating DRG growth and axon extension in peripheral nerve regeneration. The results showed that oriented aligned magnetic PCL/Fe3 O4 composite scaffolds were successfully prepared by electrospinning technique and possessed good mechanical properties and magnetic responsiveness...

Cancer, a chronic disease characterized by uncontrolled cell development, kills millions of people globally. The WHO reported over 10 million cancer deaths in 2020. Anticancer medications destroy healthy and malignant cells. Cancer treatment induces neuropathy. Anticancer drugs cause harm to spinal cord, brain, and peripheral nerve somatosensory neurons, causing chemotherapy-induced neuropathic pain. The chemotherapy-induced mechanisms underlying neuropathic pain are not fully understood. However, neuroinflammation has been identified as one of the various pathways associated with the onset of chemotherapy-induced neuropathic pain...

Poisoning with organophosphorus compounds, which can lead to a cholinergic crisis due to the inhibition of acetylcholinesterase and the subsequent accumulation of acetylcholine (ACh) in the synaptic cleft, is a serious problem for which treatment options are currently insufficient. Our approach to broadening the therapeutic spectrum is to use agents that interact directly with desensitized nicotinic acetylcholine receptors (nAChRs) in order to induce functional recovery after ACh overstimulation. Although MB327, one of the most prominent compounds investigated in this context, has already shown positive properties in terms of muscle force recovery, this compound is not suitable for use as a therapeutic agent due to its insufficient potency...

Of all chemical warfare agents (CWAs), only nerve and blood agents cause massive mortality at low concentrations. To better detect and discriminate nerve and blood agents, a reliable detection method is desirable. We report a series of fluorescent probes for nerve and blood agent detection. Among the tested probes, SR-Pip detected nerve and blood agents quickly (within 10 s for nerve agents and 1 min for blood agents). SR-Pip coupled with nerve agent produced a weak orange fluorescence with good sensitivity [limit of detection (LOD)= 5...

At the synapse, presynaptic neurotransmitter release is tightly controlled by release machinery, involving the soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and Munc13. The Ca2+ sensor Doc2 cooperates with Munc13 to regulate neurotransmitter release, but the underlying mechanisms remain unclear. In our study, we have characterized the binding mode between Doc2 and Munc13 and found that Doc2 originally occludes Munc13 to inhibit SNARE complex assembly. Moreover, our investigation unveiled that EphB2, a presynaptic adhesion molecule (SAM) with inherent tyrosine kinase functionality, exhibits the capacity to phosphorylate Doc2...

BACKGROUND: Depression is a common psychiatric disorder in diabetic patients. Depressive mood associated with obesity/metabolic disorders is related to the inflammatory response caused by long-term consumption of high-fat diets, but its molecular mechanism is unclear. In this study, we investigated whether the antidepressant effect of transcutaneous auricular vagus nerve stimulation (taVNS) in high-fat diet rats works through the P2X7R/NLRP3/IL-1β pathway. METHODS: We first used 16S rRNA gene sequencing analysis and LC-MS metabolomics assays in Zucker diabetic fatty (ZDF) rats with long-term high-fat diet (Purina #5008) induced significant depression-like behaviors...

Introduction Hansen's disease is a condition in which patients develop peripheral neuropathy. In 1873, G. H. A. Hansen discovered Mycobacterium leprae, the causative agent of leprosy, a chronic infectious disease. These bacteria influence the peripheral nerves, which is likely to cause neuropathy. Sensory nerve conduction studies were performed in leprosy patients on the upper limb nerves of 30 patients in the rural area of the Wardha district in the Indian population. Methods In this study, we recruited 30 leprosy patients from the Department of Dermatology and A...

Neuronal voltage-gated KCNQ (Kv7) channels, expressed centrally and peripherally, mediate low-threshold and non-inactivating M-currents responsible for the control of tonic excitability of mammalian neurons. Pharmacological opening of KCNQ channels has been reported to generate analgesic effects in animal models of neuropathic pain. Here, we examined the possible involvement of central KCNQ channels in the analgesic effects of retigabine, a KCNQ channel opener. Behaviorally, intraperitoneally applied retigabine exerted analgesic effects on thermal and mechanical hypersensitivity in male mice developing neuropathic pain after partial sciatic nerve ligation, which was antagonized by the KCNQ channel blocker XE991 preadministered intraperitoneally and intrathecally...

BACKGROUND: Hypothermia is a promising therapy for traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI patients in clinical studies are inconsistent due to several severe side effects. Here, an injectable refrigerated hydrogel was designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. Hydrogel has four advantages: (1) It can be injected into injured sites after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling...

Different techniques have been described for glenoid fractures, there is still a need for safe and effective agents to promote outcomes. From January 2016 to April 2021, the clinical data of 17 patients with pulley type IA fractures treated by the V-shaped fixation technique under shoulder arthroscopy were retrospectively analyzed. Preoperative X-ray, CT, and MRI examinations were completed. The functional score of the shoulder joint, such as the visual analog scale (VAS), Constant score, and Modified Rowe score, was used to evaluate the preoperative and final follow-up clinical outcomes...

The ability to control the catalytic activity of enzymes in chemical transformations is essential for the design and development of artificial catalysts. Herein, we report the synthesis and characterization of functional ligands featuring two 1,4,7,10-tetraazacyclododecane units linked by an azobenzene group and their corresponding dinuclear Zn(II) complexes. We show that the configuration switching ( E/Z ) of the azobenzene spacer in the ligands and their dinuclear Zn(II) complexes is reversibly controlled by irradiation with UV and visible light...

BACKGROUND: With the improvement of emergency techniques, the survival rate of patients with severe brain injury has increased. However, this has also led to an annual increase in the number of patients with prolonged disorders of consciousness (pDoC). Hence, recovery of consciousness is an important part of treatment. With advancing techniques, noninvasive neuromodulation seems a promising intervention. The objective of this review was to summarize the latest techniques and provide the basis for protocols of noninvasive neuromodulations in pDoC...