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Introduction: Chemical mass casualty incidents (MCIs) pose a substantial threat to public health and safety, with the capacity to overwhelm healthcare infrastructure and create societal disorder. Computer simulation systems are becoming an established mechanism to validate these plans due to their versatility, cost-effectiveness and lower susceptibility to ethical problems. Methods: We created a computer simulation model of an urban subway sarin attack analogous to the 1995 Tokyo sarin incident. We created and combined evacuation, dispersion and victim models with the SIMEDIS computer simulator. We analyzed the effect of several possible approaches such as evacuation policy ('Scoop and Run' vs. 'Stay and Play'), three strategies (on-site decontamination and stabilization, off-site decontamination and stabilization, and on-site stabilization with off-site decontamination), preliminary triage, victim distribution methods, transport supervision skill level, and the effect of search and rescue capacity. Results: Only evacuation policy, strategy and preliminary triage show significant effects on mortality. The total average mortality ranges from 14.7 deaths in the combination of off-site decontamination and Scoop and Run policy with pretriage, to 24 in the combination of onsite decontamination with the Stay and Play and no pretriage. Conclusion: Our findings suggest that in a simulated urban chemical MCI, a Stay and Play approach with on-site decontamination will lead to worse outcomes than a Scoop and Run approach with hospital-based decontamination. Quick transport of victims in combination with on-site antidote administration has the potential to save the most lives, due to faster hospital arrival for definitive care. [ABSTRACT FROM AUTHOR]

This study addresses a comprehensive assessment of the interaction between chemical warfare agents (CWA) and acetylcholinesterase (AChE) systems, focus on the intriguing pnictogen‐bond interaction (PnB). Utilizing the crystallographic data from the Protein Data Bank pertaining to the AChE‐CWA complex involving Sarin (GB), Cyclosarin (GF), 2‐[fluoro(methyl)phosphoryl]oxy‐1,1‐dimethylcyclopentane (GP) and venomous agent X (VX) agents, the CWA is systematically displaced by increments of 0.1 Å along the PO bond axis, extending its distance by 4 Å from the original position. The AIM analysis was carried out and consistently revealed the presence of a significant interaction along the PO bond. Investigating the intrinsic nature of the PnB, the NBO and the EDA analysis unearthed the contribution of orbital factors to the overall energy of the system. Strikingly, this observation challenges the conventional σ‐hole explanation commonly associated with such interactions. This finding adds a layer of complexity to understanding of PnB, encouraging further exploration into the underlying mechanisms governing these intriguing chemical phenomena. [ABSTRACT FROM AUTHOR]

Nerve agents are the most notorious substances, which can be fatal to an individual because they block the activity of acetylcholinesterase. Fighting against unpredictable terrorist assaults and wars requires the simple and quick detection of chemical warfare agent vapor. In the present contribution, we have introduced a rhodamine-based chemosensor, BDHA, for the detection of nerve gas-mimicking agents diethylchlorophosphate (DCP) and diethylcyanophosphonate (DCNP) and mustard gas-mimicking agent 2-chloroethyl ethyl sulfide (CEES), both in the liquid and vapor phase. Probe BDHA provides the ability for detection by the naked eye in terms of colorimetric and fluorometric changes. It has been revealed that the interaction between nerve agents mimics and probe BDHA facilitates spirolactam ring opening due to the phosphorylation process. Thus, the highly fluorescent and colored species developed while probe BDHA is colorless and non-fluorescent due to the intramolecular spirolactam ring. Moreover, probe BDHA can effectively recognize DCP, DCNP, and CEES in the µM range despite many toxic analytes and could be identified based on the response times and quantum yield values. Inexpensive, easily carried paper strips-based test kits were developed for the quick, on-location solid and vapor phase detection of these mustard gas imitating agents (CEES) and nerve gas mimicking agents (DCP and DCNP) without needing expensive equipment or skilled personnel. More remarkably, the test strips' color and fluorescence can be rapidly restored, exposing them to triethyl amine (TEA) for cyclic use, suggesting a potential application in the real-time identification of chemical warfare agents. To accomplish the on-location application of BDHA, we have experimented with soil samples to find traces of DCP. Therefore, the chromo-fluorogenic probe BDHA is a promising, instantaneous, and on-the-spot monitoring tool for the selective detection of DCP, DCNP, and CEES in the presence of others. [ABSTRACT FROM AUTHOR]

A selective and reliable modified glassy carbon sensor, based on a 1.0% Cd zeolitic imidazole framework-67 modified glassy carbon sensor (GCS2), has been developed for ultrasensitive detection of dimethyl methyl phosphonate (DMMP) in human biological fluid. The synthesis of porous nanoparticles of Cd zeolitic imidazole framework-67 (Cd ZIF-67) was carried out via the hydrothermal method. The resulting Cd ZIF-67 powder emerges with good crystallinity, a rhombic dodecahedral morphology with particle size in the range 300 ~ 500 nm, and a specific surface area of 1780 m2·g−1. Furthermore, the fabricated sensor exhibited superior performance in the detection of DMMP with two linearity ranges of 0.02–2.0 nM and 2.0–9.0 nM and a limit of detection (LOD) of 0.06 pM. The fabricated sensor exhibited good reliability, long-term stability, and repeatability, which are favourable attributes for electroanalytical detection. In addition, the fabricated sensor displayed superior performance without significant interference during the assay of DMMP in a biological fluid (human serum sample) within two linearity ranges of 0.1–1.0 nM and 1.0–6.0 nM and a LOD of 0.03 nM. [ABSTRACT FROM AUTHOR]

Precision-cut lung slices (PCLS) are a suitable model for analyzing the acetylcholinesterase (AChE) activity and subsequent effects after exposure to organophosphorus (OP) compounds. In this study, the AChE activity was determined in intact PCLS for the first time. Since the current standard therapy for OP poisoning (atropine + oxime + benzodiazepine) lacks efficiency, reliable models to study novel therapeutic substances are needed. Models should depict pathophysiological mechanisms and help to evaluate the beneficial effects of new therapeutics. Here PCLS were exposed to three organophosphorus nerve agents (OPNAs): sarin (GB), cyclosarin (GF), and VX. They were then treated with three reactivators: HI-6, obidoxime (OBI), and a non-oxime (NOX-6). The endpoints investigated in this study were the AChE activity and the airway area (AA) change. OPNA exposure led to very low residual AChE activities. Depending on the reactivator properties different AChE reactivation results were measured. GB-inhibited PCLS-AChE was reactivated best, followed by VX and GF. To substantiate these findings and to understand the connection between the molecular and the functional levels in a more profound way the results were correlated to the AA changes. These investigations underline the importance of reactivator use and point to the possibilities for future improvements in the treatment of OPNA-exposed victims. • Acetylcholinesterase (AChE) activity determination in precision-cut lung slices (PCLS): Use of PCLS as an ex vivo model. • Comprehensive OPNA exposure and reactivation study: Exposure of PCLS to GB, GF, and VX, followed by reactivation with HI-6, OBI, and aNOX-6. • AChE reactivation results: Revealing varying reactivation efficiencies for different nerve agents: GB > VX > GF. • Correlation of molecular and functional levels: Correlating AChE activities with airway area (AA) changes. [ABSTRACT FROM AUTHOR]

The bispyridinium oxime HI-6 DMS is in development as an improved therapy for the treatment of patients exposed to organophosphorus nerve agents. The aim of the work described in this paper was to provide non-clinical data to support regulatory approval of HI-6 DMS, by demonstrating efficacy against an oxime-sensitive agent, GB and an oxime-resistant agent, GD. We investigated the dose-dependent protection afforded by therapy including atropine, avizafone and HI-6 DMS in guinea-pigs challenged with GB or GD. We also compared the efficacy of 30 mg.kg−1 of HI-6 DMS to an equimolar dose of the current in-service oxime P2S and the dichloride salt of HI-6 (HI-6 Cl 2). In the treatment of GB or GD poisoning there was no significant difference between the salt forms. The most effective dose of HI-6 DMS in preventing lethality following challenge with GB was 100 mg.kg−1; though protection ratios of at least 25 were obtained at 10 mg.kg−1. Protection against GD was lower, and there was no significant increase in effectiveness of HI-6 DMS doses of 30 or 100 mg.kg−1. For GD, the outcome was improved by the addition of pyridostigmine pre-treatment. These data demonstrate the benefits of HI-6 DMS as a component of nerve agent therapy. © Crown copyright (2023), Dstl. • A comprehensive assessment in the guinea-pig of the efficacy of HI-6 DMS. • HI-6 was given in combination with atropine and an anticonvulsant. • Therapy including HI-6 DMS was superior to the current oxime P2S for GB and GD. • Pyridostigmine pretreatment enhanced protection against GD poisoning. [ABSTRACT FROM AUTHOR]

Dried urine spot (DUS) is a micro-sample collection technique, known for its advantages in handling, storage and shipping. It also uses only a small volume of urine, an essential consideration in working with small animals, or in acute medical situations. Alkyl-phosphonic acids are the direct and indicative metabolites of organophosphorus chemical warfare agents (OP-CWAs) and are present in blood and urine shortly after exposure. They are therefore crucially important for monitoring casualties in war and terror scenarios. We report here a new approach for the determination of the metabolites of five CWAs in urine using DUS. The method is based on a simple and rapid sample preparation, using only 50 µL of urine, spotted and dried on DBS paper, extracted using 300 µL methanol/water and analyzed via targeted LC-MS/MS. The detection limits for the five CWAs, sarin (GB), soman (GD), cyclosarin (GF), VX and RVX in human urine were from 0.5 to 5 ng/mL. Recoveries of (40–80%) were obtained in the range of 10–300 ng/mL, with a linear response (R2 > 0.964, R > 0.982). The method is highly stable, even with DUS samples stored up to 5 months at room temperature before analysis. It was implemented in a sarin in vivo exposure experiment on mice, applied for the time course determination of isopropyl methylphosphonic acid (IMPA, sarin hydrolysis product) in mice urine. IMPA was detectable even with samples drawn 60 h after the mice's (IN) exposure to 1 LD50 sarin. This method was also evaluated in a non-targeted screening for multiple potential CWA analogs (LC-Orbitrap HRMS analysis followed by automatic peak detection and library searches). The method developed here is applicable for rapid CWA casualty monitoring. [ABSTRACT FROM AUTHOR]

When studying physical properties of highly toxic chemicals, such as chemical warfare agents (CWAs), molecular dynamics (MD) simulations can serve as an alternative to experimental measurements. We performed MD simulations to calculate viscosity of four organophosphorus liquids, CWAs, sarin, and soman, as well as their simulants, DMMP and DIMP, in the temperature range from 0 to 60∘C. The molecules were represented with Transferable Potentials for Phase Equilibria United Atom (TraPPE‐UA) force field; the calculations were performed using the Green–Kubo method. The results for sarin and DMMP are in good agreement with previously published experimental data, which justifies the use of the TraPPE‐UA force field for other organophosphorus compounds. Therefore we predicted viscosity of DIMP and soman, for which the experimental data were unavailable. Our results suggest that for applications where liquid viscosity is important, DMMP is a suitable simulant for sarin, and DIMP is a suitable simulant for soman. [ABSTRACT FROM AUTHOR]

This article shows that the Syrian Arab Republic (SAR) was doomed for destruction by the «collective West» at least since 2002 within the framework of the process of fragmentation of the states of the Greater Middle East and bringing the Muslim Brotherhood to power in these countries. Later this process was called the Arab Spring. The analysis of the alleged «facts» of the use of chemical weapons by the Syrian Armed Forces made it possible to establish that they were nothing more than primitive artificial performances. No «chemical attack» in Syria, attributed to the Syrian army, pursued military objectives. The basic principles of the use of chemical weapons in combat were ignored. Not a single case of the use of factory­loaded chemical munitions has been recorded. Information attacks of the Western media and non­governmental organizations, as well as their claims about the «Asad's regime»'s «chemical war against its own people» were carried out to support the Syrian anti­governmental forces at the time of their offensive on the government­controlled territory, or when they were defeated by the Syrian army. Since 2013 the opposition has been practicing mass abductions and murders of children in order to obtain more convincing «pictures». But these crimes did not attract any attention of the Western governments or human rights organizations. The article also presents the evidence of systemic failures and shortcomings in the work of the OPCW ­ UN Joint Investigative Mechanism (JIM) and the OPCW Fact Finding Mission (FFM), formed to establish the facts surrounding allegations of the use of toxic chemicals for hostile purposes in Syria. Considering staged fake chemical attack in Syria within the context of modern geopolitics, we can assume that it is possible to talk about the new «crusade» on Russia and its allies, but with the use of weapons of mass destruction. After the retrospective analysis of the mechanisms of information warfare, we may also note the deep intellectual degradation of its organizers in comparison with the similar information operations of the 1990s. This circumstance poses a serious threat not only to Syria and Russia, but to other countries as well, because the organizers of these operations are unable to assess even the immediate impacts of their actions.

Sea anemones are well-spread everywhere in the World Ocean and represent the most ancient active poisonous organisms. Their main instrument of attack on other animals are the nematocysts – stinging organelles with the curtailed hollow thread with poisonous edge on the end. In order to attract their potential victims, they use fluorescent proteins. These proteins became a separate object of research as genetically coded markers for the observation of activity of promotors of genes. The poisonous secret of sea anemones is characterized by the presence of maximum number of peptides of various structural classes and spatial structures among the studied land and marine organisms (bees, spiders, scorpions, snakes ect.). This fact complicates the identification of sea anemones' secret and its differentiation from poisons of animals of other taxons, if the concrete source of its origin is unknown. The toxicity of some biologically active sea anemone peptides (RpI, RpIII) at intravenous administration to experimental animals is comparable with that of the most well-known and dangerous representatives of natural toxins with the similar mechanism of action (an alpha-hemolysine and tetrodotoxin), or chemical warfare agents, such as sarin and hydrogen cyanide. Based on their toxic effect, the biologically active sea anemone peptides generally can be classified as neurotoxins due to their impact on the functioning of sodium channels in the cells of the nervous system of animals. Cardiotoxic effect of sea anemone secret is caused by the specificity of interaction between its separate neurotoxins and one of the sub-types of sodium channels of muscle cells, characteristic for heart tissues. The main ways of identification of sea anemone neurotoxins in samples (for example, during the investigation of biological crimes) can be sequence by Edman`s method or tandem mass spectrometry (the analysis of fragments of toxin molecule for the establishment of its structure). Further study on the mechanisms of interaction between the sea anemone neurotoxins and the ion channels of the cells of nervous and muscular systems may result in the creation of medicines for treatment of channelopathy, as well as pluripotential antidotes, blocking the toxins, that influence on sodium channels.

The Iraqis became the first nation to use chemical weapons on the modern battlefield during the IranIraq War (1980-1988). There are no general reviews and research available on this issue in Russian. It also puts the Russian researchers in an unequal position in comparison with their Western and Middle Eastern colleagues, who have such information from a wide range of sources. This lack of knowledge limits our ability to understand the secret mechanisms that trigger modern chemical wars in the Middle East. The analysis in the present study is based on different Western sources, UN and CIA materials. The article shows that Iraq – a third world country with the population of 16,3 million people in 1980-ies and relatively low educational level – could start its chemical weapons program only due to the Western aid and assistance (supplies of the precursors, technologies and technical documentation, education of specialists, diplomatic support ect). Only due to this assistance the Iraqi`s chemical weapons program could become successful. The industrial production of chemical agents and chemical munitions of various tactical purposes was established by the Iraqis in less than 10 years. By the end of the 1980-ies, the Iraqi chemists laid the foundations of the future research in the sphere of toxic chemicals. The industrial base for the production of CW have also been established. For Russia, the success of the Iraq`s chemical weapons program is a warning. It means that technically backward, but oil rich quasi-state can acquire chemical weapons in a few years with the clandestine support of the same «sponsors», and use it both for provocations and for conducting combat operations in the regions, vital for Russia`s interests.

The third article in the series is dedicated to the medical consequences of the chemical warfare between Iran and Iraq during the war (1980–1988). The UN official documents and materials, declassified CIA documents, as well as other open Western and Iranian sources have been used during its preparation. The chemical war against the Islamic Republic of Iran was waged in the conditions of the increased power of chemical weapons, when the Iraqi army had the opportunity to carry out multiple massive chemical aviation strikes at operational depth and to use multiple launch rocket systems for the massive use of toxic substances in the tactical zone. The mortality from sulfur mustard reached 30 % in some sections of the front, that was impossible during the First World War. The unpreparedness of the Iranian army to chemical warfare led to the serious irretrievable losses among the Iranian military during the war (25 thousand people) and to the grave long-term consequences for the health of the survivors (at least 100 thousand people), despite of the relatively small amount of poisonous substances used by Iraq (2.54 thousand tons). As in World War I, sulfur mustard turned out to be the «king of gases» in this war. The Iranian scientists find out that even after the curing of acute lesions in hospitals the pathological process caused by the action of poisonous substances does not stop. It enters the phase of delayed effects, manifested with the age of the patient. There are the irreversible obstructive processes in the lungs («mustard lung»). In 2014 about 45 thousand Iranians suffered from late respiratory complications caused by sulfur mustard. There are the eczemoid dermatitis, vitiligo, psoriasis and discoid lupus erythematosus. There are the delayed ulcerative keratitis and various lesions in the neurological tissues of the eye and in the ocular fundus of the vascular system. There are other pathologies as well. The article contains a large number of photographs, diagrams and images, never published in Russian medical literature before.

The Iran-Iraq war (1980–1988) was the first modern war in which chemical weapons were used. The purpose of this work is to summarize the experience of treating victims, affected by nerve agents. The publications of Iranian authors in different scientific journals were used for the preparation of the article. The first use of chemical weapons by the Iraqi army occurred in August 1983 in Kurdistan (sulfur mustard). Nerve agent (tabun) was first used on February 29, 1984 in the battles for the Majnun Islands. In total, 140 tons of tabun and about 600 tons of sarin / cyclosarin were used against Iranian troops during the war. Around 5.5 thousand servicemen died directly from the nerve agents. For one dead from tabun, there were at least 7 poisoned people who needed qualified toxicological assistance; lethal outcomes among servicemen affected by the herd amounted to at least 15%. Military personnel without protective equipment, who received large doses of nerve agents, lost consciousness within 30 seconds and died in positions within a few minutes. The most sensitive to such agents were women, children and the elderly, who accidentally fell under a chemical attack. The use of nerve agents by the enemy was accompanied by panic in the troops and the arrival of a huge number of military personnel in critical condition at medical stations. Sweating, fasciculations and miosis were the first clinical signs by which those affected by such toxic agents were recognized. The effectiveness of antidote therapy (atropine + oxime + diazepam) depended on the time of medical care. The most effective was the use of atropine by titration (fractional intravenous drip) to achieve ease of breathing, absence of bronchospasm, disappearance of secretions from the respiratory tract and heart rate >80 beats/min. The oximes turned out to be not effective in the treatment of those poisoned by tabun. The most effective was degassing by physical removal of toxic chemical. Degassing of the affected had to be carried out by washing with sea or river water, using solutions of chlorine-containing household chemicals, and sprinkling with dry earth.

INTRODUCTION: We simulated an on-site, multi-hospital mass casualty incident (MCI) to educate emergency medicine providers in the principles of trauma resuscitation and collaboration with administration and staff during an MCI. METHODS: We implemented high-fidelity manikins, inflatable manikins, and actors to simulate a sarin gas bombing. Learners triaged patients at a decontamination tent using the simple triage and rapid treatment (START) tool, or they participated in a simulation in a resuscitation bay. RESULTS: Forty participants anonymously rated the learning impact of the exercise, the clinical relevance to emergency medicine, and the effectiveness of the faculty facilitation and debriefing on a 1-5 Likert scale. The average responses to all questions were 4.45 or greater, and 98% of respondents recommended adding the scenario to the standard curriculum. DISCUSSION: We successfully executed a novel, multihospital, MCI drill that was rated to be a better alternative to sequential simulation in a simulation center. [ABSTRACT FROM AUTHOR]

The host–guest chemistry of O,O′-diisopropyl fluorophosphate (DFP), a phosphonofluoridate G-series chemical warfare agent simulant, was investigated in the presence of a number of octanuclear cubic coordination cage hosts. The aim was to demonstrate cage-catalysed hydrolysis of DFP at near neutral pH: however, two octanuclear coordination cages, HPEG (containing water-solubilising PEG groups) and HW (containing water-solubilising hydroxymethyl groups), were actually found to increase the lifetime of DFP in aqueous buffer solution (pH 8.7). Crystallographic analysis of DFP with a structurally related host cage revealed that DFP binds to windows in the cage surface, not in the internal cavity. The phosphorus–fluorine bond is directed into the cavity rather than towards the external environment, with the cage/DFP association protecting DFP from hydrolysis. Initial studies with the chemical warfare agent (CWA) sarin (GB) with HPEG cage in a buffered solution also showed a drastically reduced rate of hydrolysis for sarin when bound in the host cage. The ability of these cages to inhibit hydrolysis of these P–F bond containing organophosphorus guests, by encapsulation, may have applications in forensic sample preservation and analysis. [ABSTRACT FROM AUTHOR]

Abstract Gulf War Illness (GWI) encompass a spectrum of maladies specific to troops deployed during the Persian Gulf War (1990–1991). There are several hypothesized factors believed to contribute to GWI, including (but not limited to) exposures to chemical agents and a foreign environment (e.g., dust, pollens, insects, and microbes). Moreover, the inherent stress associated with deployment and combat has been associated with GWI. While the etiology of GWI remains uncertain, several studies have provided strong evidence that chemical exposures, especially neurotoxicants, may be underlying factors for the development of GWI. This mini style perspective article will focus on some of the major evidence linking chemical exposures to GWI development and persistence decades after exposure.

Chemical agents have been utilized for centuries in warfare and pose a health threat to civilians and military personnel during armed conflict. Despite treaties and regulations against their use, chemical agent exposure remains a threat and measures to understand their effects and countermeasures for systemic and organ-specific health are needed. Many of these agents have ocular complications, both acute and chronic. This mini-review focuses on key chemical agents including vesicants (mustards, lewisite), nerve agents (sarin, VX), knockdown gasses (hydrogen cyanide), and caustics (hydrofluoric acid). Their ophthalmic manifestations and appropriate treatment are emphasized. Acute interventions include removal of the source and meticulous decontamination, as well as normalization of pH to 7.2–7.4 if alteration of the ocular pH is observed. Besides vigorous lavage, acute therapies may include topical corticosteroids and non-steroid anti-inflammatory therapies. Appropriate personal protective equipment (PPE) and strict donning and doffing protocols to avoid healthcare provider exposure are also paramount in the acute setting. For more severe disease, corneal transplantation, amniotic membrane graft, and limbal stem cell transplantation may be needed. Orbital surgery may be required in patients in whom cicatricial changes of the ocular surface have developed, leading to eyelid malposition. Multidisciplinary care teams are often required to handle the full spectrum of findings and consequences associated with emerging chemical threats.

Context: In contrast to un-catalyzed hydrolysis of organophosphorus (OP) compounds, metal ions or/and their complexes with chelating ligands show catalytic effects in several ways depending upon the nature of the metal, ligand, substrate, and medium. It is known that Cu(II)-en chelate containing copper complexes accelerate the hydrolysis of OP compounds. However, the mechanism for this rate enhancement in the Cu(II)-en chelate catalytic hydrolysis reaction of sarin remains unexplored. We have examined possible mechanisms involving a Cu(II)-en with hydroxide nucleophile for the reaction pathway of the hydrolysis of O-isopropyl methylphosphonofluoridate (sarin) computationally. The density functional (B3LYP) employed in this study has reproduced the experimental Gibb's free energy of activation value 15.5 kcal/mol for alkaline hydrolysis of sarin. Earlier proposal of push–pull mechanism for metal ion chelate-catalyzed hydrolysis of OP compounds has been found to be unfavorable in the present study. The role of water molecules in catalyzing the hydrolysis of sarin with Cu(II)-en chelate is crucial. The catalytic process involving Cu(II)-en chelate with one water molecule is the more plausible pathway to achieve the hydrolysis of sarin with Cu(II)-en chelate complexes. Methods: The most popular B3LYP method was used for optimization of given geometries. Except LANL2DZ for Cu atom, all the atoms are described using the 6–31 + G(d) basis set. The stability test has been performed for the wave functions as we are dealing with the open-shell molecules in order to ensure stable electronic configuration form, and the stable wavefunction is used as the initial configuration for the subsequent optimization. Harmonic frequency calculations and thermodynamic corrections were performed at the same level of theory. PCM method has been used for solvation effects. In order to ensure that each saddle point is linked to a minimum, IRC calculations were performed in forward and reverse directions to ensure the eigenvectors associated with the unique negative eigenvalues of the Hessian matrix. All energies discussed are solvated Gibbs free energies corrected to 298.15 K for the relative stability of the chemical structure. All calculations were performed using the Gaussian 09 code. [ABSTRACT FROM AUTHOR]

Nerve agents have been used recently in the Syrian civil war. Collecting relevant samples for retrospective identification of an attack is often problematic. The article deals with the possibility of using contaminated gloves as an analytical sample for evidence of the chemical weapons use. There have not yet been published studies dealing with the identification of chemical warfare agents in this type of matrix, where the diversity of chemical properties of gloves and the lifetime of the contaminated sample would be considered. Sarin, soman, and cyclosarin were used as contaminants in the study. Nitrile, latex, and vinyl disposable gloves were chosen as matrices. The identification method was gas chromatography. Six solvents commonly used in military laboratories were tested as extractants. The extraction procedure was optimized in terms of the appropriate method (vortex) and the required extraction time (1 min) and resulted in significant reduction in sample preparation time. The chromatographic background of the extracts was also monitored in order to find a method with the least number of peaks interfering in the identification. Suitable solvents were hexane and acetonitrile. The lifetime of the sample was also investigated. The worst result was recorded for latex. For individual contaminants, the time varied depending on the volatility. The developed procedures were successfully validated within a sample handling effects scenario. The results demonstrate that in the event of an ongoing military risk at the site of an attack, even discarded disposable rubber glove type samples can be used as evidence. [ABSTRACT FROM AUTHOR]

The name of Korkut has long attracted the attention of the world scientific community. In the folklore of many Turkic peoples related to the ancient Oghuz tribes, there are legends and myths about Korkut, which describe the heroic deeds of the Oghuz heroes. The legacy of the legendary Korkut's music and epic has attracted the attention of researchers since the middle of the 19th century. Scholars from Russia, Türkiye, Azerbaijan, Turkmenistan and Kazakhstan have written a wide number of research papers, which highlighted the problems associated with the main epic legacy of Oghuz antiquity -- "The Book of Dede Korkut" or "The Book of Korkut Ata". The literary artifacts associated with the name of the legendary Korkut have gained worldwide fame. Both versions of the Oghuz manuscript "Kitab-ı Dede Korkut Ala Lisan-ı Taife-i Oğuzan" (Dresden) and "Hikâyat-i Oğuznâme-i, Kazan Beğ ve Gayrı" (Vatican), which have come down to us, are now the focus of scientific consideration. The abundance of cognitive information and onomastic names in the epic increasingly attracts the attention of folklorists. It is no secret that in the Kazakh folklore of the early 20th century, the Soviet ideology imposed a ban on the development of the epic heritage of Korkut. Moreover, closer to the middle of the 20th century, the Oghuz heroic epic was evaluated as a creative product of the feudal era. For this reason, some peoples of Oghuz origin openly ignored the folk heritage. Korkut is a representative of the Oghuz tribe. In addition, his name has existed in Kazakh folklore for a very long time. Even before the 1917 Revolution, several legends about the Korkut tombstone were recorded by famous ethnographers. Kazakh scholars began to study folklore materials about Korkut at the turn of the 1970s. This topic was first voiced by Professor Auelbek Konratbayev, who published several articles, then translated V. V. Bartold's edition of "The Book of my grandfather Korkut" into Kazakh. In recent decades, especially after the gaining of independence, folklorists, musicologists, and performing musicians have begun to deal with this problem. It got to the point that some of them started talking about the newly found legacy of the legendary Korkut - musical compositions for the bowed instrument - kylkobyz. Without referring to reliable sources, without arguing the origin of the newly discovered musical compositions attributed to Korkut, individual authors began to publish their rather detailed research in the form of scientific articles and even books. Despite the existing criticism in international publications, the wave of pseudo-researchers is growing. The questions related to the heritage of Korkut are overgrown with all sorts of tall tales of indefinite origin. This article attempts to conduct a scientific analysis of numerous studies published in the recent years on the pages of both foreign and local press. The works of individual novice authors who are engaged in inflating the number of legends associated with the name of Korkut are subjected to special consideration. In this regard, the article emphasizes that the classic version of the Kazakh legend of Korkut was published by V. Velyaminov- Zernov in the second half of the 19th century. Despite the presence of a published text, this legend has been freely interpreted by individual authors. Another legend, once published by A. Zhubanov without reference to the original source, also requires close study. This article is based on scientific problems related to the music and epic heritage of Korkut. It highlights the stages of mastering the musical heritage of Korkut and the legends associated with them. Much attention is paid to detailed, comparative analysis and the study of primary sources. In the process of developing the theme, all the changes that have occurred since the beginning of the development of the musical heritage of Korkut are identified. The legends that allegedly arose in connection with his music are also subjected to scientific analysis. Through the prism of hermeneutical analysis, the musical melodies attributed to Korkut are also studied. A special attention is drawn to the reliability of previ ously unknown primary sources that have begun to enter scientific realm. At the same time, the artistic features and scientific significance of these musical tunes are analyzed. Only in recent years, several articles about Korkut's musical heritage have been published on the pages of foreign scientific publications. They have become the focus of this article. In the recent years previously unknown legends, which have been claimed to be preserved in Kazakh folklore, have appeared in the literature. The admirers of Korkut's name are trying hard to connect these immature plots with the name of the legendary Korkut. Moreover, some researchers started talking about the musical heritage of Korkut, which is not known not only to the Turkic world, but also to the scientific world. As the primary source, they began to refer to the religious and mystical tunes of Nishan Shamenuly, who lived in the second half of the 20th century, from whom the musical tunes "saryn" and "sarnau" were recorded. This article attempts to determine the origin of the music and religious tunes of Nishan, because the aforementioned sweeping statements are circulated without taking into account the centuries-old performing tradition of the kobyz, some of which has not even reached our times. Without much detailed research so-called previously unknown musical heritage of medieval Korkut have been introduced to the whole world. Moreover, these same tunes, which have nothing to do with the legendary Korkut, were included in the UNESCO list as an example of the intangible culture of medieval antiquity. All these questions formed the main problem of the given article. [ABSTRACT FROM AUTHOR]

A new Mean Sea Surface (MSS) called DTU21MSS for referencing sea level anomalies from satellite altimetry is introduced in this paper and a suite of evaluations are performed. One of the reasons for updating the existing Mean Sea Surface is the fact, that during the last 6 years nearly three times as much data have been made available by the space agencies, resulting in more than 15 years of altimetry from Long Repeat Orbits or Geodetic Missions. This includes the two interleaved long repeat cycles of Jason-2 with a systematic cross-track distance as low as 4 km. A new processing chain with updated filtering and editing has been implemented for DTU21MSS. This way, the DTU21MSS has been computed from 2Hz altimetry in contrast to the former DTU15MSS/DTU18MSS which were computed from 1 Hz altimetry. The new DTU21MSS is computed over the same 20-year averaging time from 1993.01.01 to 2012.12.31 with a well-specified central time of 2003.01.01 and is available from the following site; https://doi.org/10.11583/DTU.19383221.v1, Andersen, 2022) Cryosat-2 employs SAR and SARin modes in a large part of the Arctic Ocean due to the presence of sea ice. For SAR and SARin mode data we applied the SAMOSA+ physical retracking in order to make it compatible with the physical retracker used for conventional Low-Resolution Mode data in other parts of the ocean. [ABSTRACT FROM AUTHOR]

Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) represents a numerical classification of any chemical to be a drug candidate with promising therapeutic efficacy with minimum toxicity or sensitivity depending on its chemical structures and its physicochemical properties. Sarin (GB) and Soman (GD) are nerve agents classified as chemical warfare agent containing phosphorous atom. Acetylcholine (ACh) as a neurotransmitter esterifies by acetyl cholinesterase enzyme (AChE) that can be irreversibly inhibited by (GB and GD) meaning termination of muscle function. Here, new in Silico predication of two nerve agents (Sarin and Soman) was done. These organophosphorous agents were hypothetically subjected to a reaction with lactic acid and various amino acids. New P-O with lactic acid and P-N linkage was between Sarin or Soman and different amino acids. Both reactions were through fluorine atom with hydroxyl group (P-O formation) and with amine (P-N). The ADMET and Druglikeness properties of the parent chemical warfare agents and their hypothetical products were subjected to MarvinSketch program and preadmet website. Sarin and Soman and their hypothetical products showed many noticeable characters such as: all 20 tested compounds were with non- inhibition character of Pgp and CYp-2D6; substrate character with CYP-3A4, negative values to skin permeability, negative to Carcino-Mouse, low risk to hERG inhibition. Other calculated predictors were varied in response between all calculated compounds.

Simple Summary: Sarin is a potent organophosphate nerve agent that is a representative of a chemical weapon and poses a threat to human health. In this study, the effects of repeated low-level sarin exposure on the cognitive behavior of rats were studied, and the activity of AChE activity and dendritic spine density in the hippocampus were measured. Whole-transcriptome and bioinformatics methods were used to analyze the related molecular mechanisms, and finally, the ceRNA regulatory network was constructed and analyzed. These newly discovery techniques provide a theoretical basis for the mechanism of sarin-induced cognitive impairment and also offer new insights for the research of other organophosphorus toxicants. Sarin is a potent organophosphorus nerve agent that causes cognitive dysfunction, but its underlying molecular mechanisms are poorly understood. In this study, a rat model of repeated low-level sarin exposure was established using the subcutaneous injection of 0.4 × LD50 for 21 consecutive days. Sarin-exposed rats showed persistent learning and memory impairment and reduced hippocampal dendritic spine density. A whole-transcriptome analysis was applied to study the mechanism of sarin-induced cognitive impairment, and a total of 1035 differentially expressed mRNA (DEmRNA), including 44 DEmiRNA, 305 DElncRNA, and 412 DEcircRNA, were found in the hippocampus of sarin-treated rats. According to Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Protein–Protein Interaction (PPI) analysis, these DERNAs were mainly involved in neuronal synaptic plasticity and were related to the pathogenesis of neurodegenerative diseases. The circRNA/lncRNA–miRNA–mRNA ceRNA network was constructed, in which Circ_Fmn1, miR-741-3p, miR-764-3p, miR-871-3p, KIF1A, PTPN11, SYN1, and MT-CO3 formed one circuit, and Circ_Cacna1c, miR-10b-5p, miR-18a-5p, CACNA1C, PRKCD, and RASGRP1 constituted another circuit. The balance between the two circuits was crucial for maintaining synaptic plasticity and may be the regulatory mechanism by which sarin causes cognitive impairment. Our study reveals the ceRNA regulation mechanism of sarin exposure for the first time and provides new insights into the molecular mechanisms of other organophosphorus toxicants. [ABSTRACT FROM AUTHOR]

Introduction Sarin is a highly toxic organophosphorus nerve agent that irreversibly inhibits neuronal enzyme acetylcholinesterase. In the prevailing scenario, it is of paramount importance to develop early diagnosis and medical countermeasures for sarin exposure. A deeper understanding of the molecular mechanism of sarin intoxication and perturbations in the associated cellular processes is likely to provide valuable clues for the elucidation of diagnostic markers and therapeutic targets for sarin exposure. Methods Present study, uncovered the changes in phosphorylation patterns of multiple proteins in different rat brain regions after sarin intoxication using 2-DE/MS approach. It provided a holistic view of the phosphorylation-mediated changes in the cellular proteome and highlighted various signaling and response pathways affected at an early time point of sarin intoxication. Results We found total 22 proteins in the cortex, 25 proteins in the corpus striatum, and 17 proteins in the hippocampus, showed ≥1.5 fold changes (hyper- or hypo- phosphorylated) with respect to control, either at 2.5 h or 1 d after sarin exposure. These results indicated the differential expression of phosphoproteins involved in protein folding in the endoplasmic reticulum, carbon metabolism, metabolic function, and energy metabolism. Conclusion Four candidates (protein disulfide-isomerase A3, heat shock cognate 71 kDa protein, alpha-enolase, and creatine kinase B-type), hyperphosphorylated in all three brain regions, can be further studied to understand the molecular mechanism behind neurodegenerative changes mediated by sarin exposure. The study sheds light on major pathogenic processes initiated during sarin intoxication and provides putative diagnostic markers/therapeutic targets for further validation. [ABSTRACT FROM AUTHOR]

Gulf War Illness (GWI) encompass a spectrum of maladies specific to troops deployed during the Persian Gulf War (1990–1991). There are several hypothesized factors believed to contribute to GWI, including (but not limited to) exposures to chemical agents and a foreign environment (e.g., dust, pollens, insects, and microbes). Moreover, the inherent stress associated with deployment and combat has been associated with GWI. While the etiology of GWI remains uncertain, several studies have provided strong evidence that chemical exposures, especially neurotoxicants, may be underlying factors for the development of GWI. This mini style perspective article will focus on some of the major evidence linking chemical exposures to GWI development and persistence decades after exposure. [ABSTRACT FROM AUTHOR]

In the last decades, Chemical, Biological, Radiological and Nuclear (CBRN) threats have become serious risks prompting countries to prioritize preparedness for such incidents. As CBRN scenarios are very difficult and expensive to recreate in real life, computer simulation is particularly suited for assessing the effectiveness of contingency plans and identifying areas of improvement. These computer simulation exercises require realistic and dynamic victim profiles, which are unavailable in a civilian context. In this paper we present a set of civilian nerve agent injury profiles consisting of clinical parameters and their evolution, as well as the methodology used to create them. These injury profiles are based on military injury profiles and adapted to the civilian population, using sarin for the purpose of illustration. They include commonly measured parameters in the prehospital setting. We demonstrate that information found in military sources can easily be adjusted for a civilian population using a few simple assumptions and validated methods. This methodology can easily be expanded to other chemical warfare agents as well as different ways of exposure. The resulting injury profiles are generic so they can also be used in tabletop and live simulation exercises. Modeling and simulation, if used correctly and in conjunction with empirical data gathered from lessons learned, can assist in providing the evidence practices for effective and efficient response decisions and interventions, considering the contextual factors of the affected area and the specific disaster scenario.

Dried urine spot (DUS) is a micro-sample collection technique, known for its advantages in handling, storage and shipping. It also uses only a small volume of urine, an essential consideration in working with small animals, or in acute medical situations. Alkyl-phosphonic acids are the direct and indicative metabolites of organophosphorus chemical warfare agents (OP-CWAs) and are present in blood and urine shortly after exposure. They are therefore crucially important for monitoring casualties in war and terror scenarios. We report here a new approach for the determination of the metabolites of five CWAs in urine using DUS. The method is based on a simple and rapid sample preparation, using only 50 µL of urine, spotted and dried on DBS paper, extracted using 300 µL methanol/water and analyzed via targeted LC-MS/MS. The detection limits for the five CWAs, sarin (GB), soman (GD), cyclosarin (GF), VX and RVX in human urine were from 0.5 to 5 ng/mL. Recoveries of (40–80%) were obtained in the range of 10–300 ng/mL, with a linear response (R2 > 0.964, R > 0.982). The method is highly stable, even with DUS samples stored up to 5 months at room temperature before analysis. It was implemented in a sarin in vivo exposure experiment on mice, applied for the time course determination of isopropyl methylphosphonic acid (IMPA, sarin hydrolysis product) in mice urine. IMPA was detectable even with samples drawn 60 h after the mice’s (IN) exposure to 1 LD50 sarin. This method was also evaluated in a non-targeted screening for multiple potential CWA analogs (LC-Orbitrap HRMS analysis followed by automatic peak detection and library searches). The method developed here is applicable for rapid CWA casualty monitoring.

Approximately 30% of the veterans who fought in the 1991 Gulf War (GW) suffer from a disease called Gulf War Illness (GWI), which encompasses a constellation of symptoms including cognitive deficits. A coalescence of evidence indicates that GWI was caused by low-level exposure to organophosphate pesticides and nerve agents in combination with physical stressors of the battlefield. Until recently, progress on mechanisms and therapy had been limited to rodent-based models. Using peripheral blood mononuclear cells from veterans with or without GWI, we recently developed a bank of human induced pluripotent stem cells that can be differentiated into a variety of cellular fates. With these cells, we have now generated cerebral organoids, which are three-dimensional multicellular structures that resemble the human brain. We established organoid cultures from two GW veterans, one with GWI and one without. Immunohistochemical analyses indicate that these organoids, when treated with a GW toxicant regimen consisting of the organophosphate diisopropyl fluorophosphate (a sarin analog) and cortisol (to mimic battlefield stress), display multiple indicators consistent with cognitive deficits, including increased astrocytic reactivity, enhanced phosphorylation of tau proteins, decreased microtubule stability, and impaired neurogenesis. Interestingly, some of these phenotypes were more pronounced in the organoids derived from the veteran with GWI, potentially reflecting a stronger response to the toxicants in some individuals compared to others. These results suggest that veteran-derived human cerebral organoids not only can be used as an innovative human model to uncover the cellular responses to GW toxicants but can also serve as a platform for developing personalized medicine approaches for the veterans. [ABSTRACT FROM AUTHOR]

Over 40% of veterans from the Persian Gulf War (GW) (1990–1991) suffer from Gulf War Illness (GWI). Thirty years since the GW, the exposure and mechanism contributing to GWI remain unclear. One possible exposure that has been attributed to GWI are chemical warfare agents (CWAs). While there are treatments for isolated symptoms of GWI, the number of respiratory and cognitive/neurological issues continues to rise with minimum treatment options. This issue does not only affect veterans of the GW, importantly these chronic multisymptom illnesses (CMIs) are also growing amongst veterans who have served in the Afghanistan-Iraq war. What both wars have in common are their regions and inhaled exposures. In this review, we will describe the CWA exposures, such as sarin, cyclosarin, and mustard gas in both wars and discuss the various respiratory and neurocognitive issues experienced by veterans. We will bridge the respiratory and neurological symptoms experienced to the various potential mechanisms described for each CWA provided with the most up-to-date models and hypotheses. [ABSTRACT FROM AUTHOR]

The Journal of Political Economy would like to acknowledge the assistance of numerous individuals who have served as referees for the journal. The list includes a wide range of names from various backgrounds and expertise. This information may be useful for library patrons conducting research on specific topics and seeking diverse perspectives. [Extracted from the article]

[Display omitted] • Analysis of HOMO, LUMO, and ESP confirmed the adsorption capability of Carbon Nano CNCs toward GB and GA, indicating their potential as carriers for targeted nerve agents. • The inner region (P1) of CNCs exhibits superior adsorption efficacy than the outer one. • A greater affinity is evidenced at a higher concentration of adsorbent/adsorbate ratio. • The interaction nature (van der Waals forces.) was proved via the Non-Covalent Interaction (NCI) plots. • MC and MD simulations provided molecular insights into adsorption of nerve agents. Carbon NanoCones (CNCs), distinguished by their conical shape and large surface area, are evaluated for their potential application in nerve gas [tabun (GA) and sarin (GB)] adsorption. Density Functional Theory (DFT) calculations, Molecular Dynamics (MD), and Monte Carlo (MC) simulations are employed to investigate this phenomenon comprehensively. The study findings indicate that tabun (GA) and sarin (GB) undergo spontaneous adsorption, characterized by significant negative energy values. Density Functional Theory (DFT) calculations indicate electron donation tendencies of nerve agents to CNC surfaces. Computational analysis shows higher adsorption efficiency in the inner portion (P1) of CNCs. Molecular Dynamics (MD) and Monte Carlo (MC) simulations confirm planar adsorption configurations parallel to CNC surfaces. The DFT calculations show that GA has a far greater adsorption energy on a Carbon Nanocone compared to GB (−44.96 kcal/mol for GA, whereas GB has an adsorption energy of −35.95 kcal/mol). Furthermore, the analysis reveals significant differences between Sarin and Tabun nerve agents. Sarin exhibits higher global hardness, indicating increased stability, while Tabun shows higher overall softness, suggesting greater reactivity. Despite similar electronegativities, Sarin's greater ionization energy and electron affinity imply enhanced stability and reactivity. Differences in HOMO and LUMO energies highlight unique reactivity profiles, with Sarin being more susceptible to nucleophilic attacks and Tabun to electrophilic attack. Sarin's larger energy gap between HOMO and LUMO orbitals signifies its superior stability under electronic disturbances. [ABSTRACT FROM AUTHOR]

A series of oxovanadium(V) compounds 1–4 were prepared and explored as stereodynamic chiroptical probes to detect a simulant of sarin known as diethyl chlorophosphate (DCP) without any interference from the competing analytes. Simultaneous CD cum UV/vis based bimodal instant recognition of DCP using optically active probes is unprecedented. Upon fabricating the vanadium compound with a polymer has yielded a chiroptical membrane, which showed a change in its dichroic as well as colorimetric signals on interaction with DCP vapour at 1 ppm. EPR and UV/vis studies revealed an irreversible change of the CD-active V(V) to the CD-silent ternary V(V) species in presence of DCP via a transient V(IV) species. Nucleophilic attack of the alkoxo oxygen of 1–4 to the electrophilic P atom of DCP resulted in the formation of ternary V(V) compounds as confirmed by 51V/31P NMR. [ABSTRACT FROM AUTHOR]

Sarin was used as a chemical weapon due to its high neurotoxicity and mortality. Subacute sarin induced cognitive and behavioral disorder. However, the underlying mechanism is still unclear. Here we offered a multi-omic approach for the analysis of altered metabolites, lipids, and proteins to explore the neurotoxicity of subacute sarin. Guinea pigs were administered between the shoulder blades 16.8 μg/kg of sarin in a volume of 1.0 ml/kg body weight by subcutaneous injection once daily for 14 days. At the end of the final injection, guinea pigs were sacrificed, and striatum were dissected for analysis. A total of 138 different metabolites were identified in the metabolome analysis. Lipids and lipid-like molecules is the largest group (38.41%). For lipidomic analysis, a total of 216 lipids were identified. In proteomic study, over 4300 proteins were identified and quantified. By integrating these enriched components, we demonstrated that the joint pathways disturbed by subacute sarin mainly involving lipid, purine and pyrimidine metabolism in guinea pig striatum. Overall, this study highlights the powerfulness of omics platforms to deepen the understanding of nerve agents caused neurotoxicity. [Display omitted] • Subacute sarin disturbed the cognitive and motor abilities in guinea pigs. • Subacute sarin disturbed purine and pyrimidine metabolism in striatum. • Nucleotides play important roles in alleviating neurotoxicity of nerve agents. • Omics platforms are useful to deepen the understanding of nerve agents caused neurotoxicity. [ABSTRACT FROM AUTHOR]

Aluminium-doped nickel ferrite (NiFeAl3+) nanoflakes were synthesized using the hydrothermal method. This nanocomposite material was used to fabricate a high-performance gas sensor for detecting dimethyl methylphosphonate, a stimulant of sarin gas (nerve agent). The fabricated sensor demonstrated a minimum detection limit of 0.1 ppm with a sensing response of 1.25%. The sensor was stable between temperatures of 200°C and 250°C. The sensing response decreased as the relative humidity increased. The sensor achieved response and recovery time of 24 s and 38 s, respectively, at a concentration of 1 ppm (250°C). The fabricated sensor demonstrated sensitivity of 14.654 ppm−1. The synthesized nanocomposite material was characterized by scanning electron microscopy (SEM), x-ray diffraction (XRD), Fourier transform infrared spectroscopy and thermogravimetric analysis. The SEM analysis showed the formation of flakes and cube-like structures. The XRD pattern showed the crystalline nature of the nanocomposite. [ABSTRACT FROM AUTHOR]

Objectives: We investigated whether UK military personnel exposed to sarin during the 'Service Volunteer Programme' at Porton Down had increased rates of mortality or cancer incidence over a 52-year follow-up., Methods: A historical cohort study assembled from UK military records, comprising male veterans exposed to sarin during the 'Service Volunteer Programme' at Porton Down, UK (n=2975) and a comparison group of similar veterans who did not attend (n=2919). Mortality and cancer incidence data were obtained from national registries up to December 2019. Analysis was conducted using Cox regression adjusted for age, year of birth and service characteristics., Results: Over a median follow-up of 52.2 years (range 2 days to 74.6 years), 1598 (53.7%) sarin-exposed veterans and 1583 (54.3%) non-exposed veterans died. Adjusted HRs for all-cause mortality were raised for any sarin exposure (HR=1.08, 95% CI 1.01 to 1.16), two or more exposures (HR=1.25, 95% CI 1.04 to 1.49) and higher doses (air >15 mg.min/m 3 ) (HR=1.15, 95% CI 1.02 to 1.30). For cause-specific mortality, sarin exposure was associated with deaths from 'other' circulatory diseases (excludes ischaemic and cerebrovascular diseases) (HR=1.41, 95% CI 1.06 to 1.87) and alcohol-attributable deaths (HR=2.66, 95% CI 1.40 to 5.07). There was no association between sarin exposure and overall cancer incidence (HR=1.01, 95% CI 0.93 to 1.10), but cancer incidence was higher for alcohol-related neoplasms (HR=1.24, 95% CI 1.01 to 1.51)., Conclusions: Sarin exposure was associated with increased rates of mortality over a 50-year follow-up. The strongest associations were observed for deaths attributable to alcohol and 'other' circulatory diseases., Competing Interests: Competing interests: NTF is part funded by a grant from the UK Ministry of Defence and is a trustee of a charity supporting the wellbeing of the Armed Forces community. GA, TK and KMV declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Quantification of the stable isotopes within a compound aids forensic investigations as it provides a fingerprint which can determine that compound's source substrates, synthetic route, and possible mechanisms of degradation. Previous stable isotope studies have explored 13 C and 2 H measurements of the sarin precursors methylphosphonic dichloride (DC) and methylphosphonic difluoride (DF) as forensic signatures. However, these measurements required different sample preparations and measurement techniques. Orbitrap isotope ratio mass spectrometry (Orbitrap-IRMS) is a developing technique which can characterize multiple stable isotopes simultaneously. Here, we apply Orbitrap-IRMS to simultaneously observe the 13 C and 2 H content of methylphosphonic acid (MPA), the hydrolysis product of DC and DF, which can be used as a proxy for the isotopic content of DC and DF. Our method requires 20 min analyses and consumes ≈60 nmol of sample, with precisions of ≈0.9 ‰ ( 13 C) and ≈3.6 ‰ ( 2 H). We apply our method to both commercially acquired MPA and MPA obtained from the hydrolysis of commercially acquired DC. We validate our methods via comparison to elemental-analyzer isotope ratio mass spectrometry (EA-IRMS). The combined 13 C and 2 H measurement creates a more robust forensic tool than either isotope individually. Our results demonstrate the viability of Orbitrap-IRMS for chemical forensic measurements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Rapid detection of Chemical Warfare Agents (CWAs) is of great significance in protecting civilians in public places and military personnel on the battlefield. Two-dimensional (2D) molybdenum disulfide (MoS2) nanosheets (NSs) can be integrated as a gas sensor at room temperature (25°C) due to their large specific surface area and excellent semiconductor properties. However, low sensitivity and long response-recovery time hinder the pure MoS2 application in CWAs gas sensors. In this work, we developed a CWAs sensor based on in-situ niobium-doped MoS2 NSs (Nb-MoS2 NSs) via direct chemical-vapor-deposition (CVD) growth. Characterization results show that the high content of Nb elements (7.8 at%) are homogeneously dispersed on the large-area 2D structure of MoS2. The Nb-MoS2 NSs-based CWAs sensor exhibits higher sensitivity (−2.09% and −3.95% to 0.05 mg/m3 sarin and sulfur mustard, respectively) and faster response speed (78 s and 30 s to 0.05 mg/m3 sarin and sulfur mustard, respectively) than MoS2 and other 2D materials at room temperature. And the sensor has certain specificity for sarin and sulfur mustard and is especially sensitive to sulfur mustard. This can be attributed to the improvement of adsorption properties via electronic regulation of Nb doping. This is the first report about CWAs detection based on two-dimensional (2D) transition metal dichalcogenides (TMDs) sensing materials, which demonstrates that the high sensitivity, rapid response, and low limit of detection of 2D TMDs-based CWAs sensor can meet the monitoring needs of many scenarios, thus showing a strong application potential.

Gastro‐oesophageal varices are the major clinical manifestations of cirrhosis and portal hypertension. Although less frequent than oesophageal varices (EV), bleeding from gastric varices (GV) is generally more severe and associated with higher mortality and a greater risk to rebleed. According to Sarin's classification, GVs are categorized into four types based on their location within the stomach and relationship with EV. Currently, treatment options for the management of GV include beta‐blockers, endoscopic band ligation, endoscopic cyanoacrylate injection, EUS‐guided coil/cyanoacrylate injection, transjugular intrahepatic portosystemic shunts and balloon‐occluded retrograde transvenous obliteration. The best treatment strategy of GV remains controversial because of the heterogeneity of GV, lack of high‐quality data and suboptimal trial design of the studies available. The proper treatment algorithm may require adequate endoscopic and imaging evaluation by a multidisciplinary team with multiple treatment options available. This review describes the hemodynamic features of GV, pharmacological, endoscopic and interventional radiological treatment options for GV. [ABSTRACT FROM AUTHOR]

Diisopropyl methylphosphonate (DIMP) is an organophosphorus compound used as a simulant for the chemical weapon Sarin. One of the means of destruction of Sarin is incineration at high temperature, which requires a clear understanding of the high‐temperature reaction kinetics of Sarin. In this work, we study the reaction rate for thermal decomposition of DIMP in the temperature range of 762–1059 K at a pressure near 1 atm. Test conditions are carefully chosen to minimize interferences from other reactions and intermediates formed during the decomposition process. The experimental rates obtained have been fitted for the Arrhenius rate expression to get the rate parameters of the reaction r1, DIMP (C7H17O3P) = IMP (C4H11O3P) + propene (C3H6) as r1(s−1)=1015.058±0.5e−(47497±1935(calmol))/RT\begin{equation*} {r_1}\;({{s^{ - 1}}}) = {10^{15.058 \pm 0.5}}\;{e^{ - ({47497 \pm 1935({\frac{{cal}}{{mol}}})})/RT}} \end{equation*}The rate obtained in this work extended the temperature range of previous measurements (up to 800 K) and can be used in reaction kinetic models for combustion of DIMP. [ABSTRACT FROM AUTHOR]

As social media becomes increasingly ubiquitous, many events are recorded and released on social media platforms, including chemical weapon attacks. We develop an objective tool in order to evaluate brief and unstructured social media videos for analysing sarin exposure from a civilian medical pathology perspective. We developed and validated this new questionnaire using a standardized procedure that includes content domain specification, item pool generation, content validity evaluation, a pilot study, and assessment of reliability and validity. In total, 51 sarin attacks and 48 matched videos were analysed. Cronbach's α for all 20 items was 0.75, which indicates adequate internal reliability. The test–retest reliability was 0.96, which indicates good internal reliability. The inter-observer intraclass correlation coefficient was 0.97. After verifying sampling adequacy with the Kaiser–Meyer–Olkin measure and the factorability of the items with Barlett's test of sphericity, a factor analysis was performed. According to the principal axis factoring, a six-factor solution explained 51.86% of the total variance. The receiver-operating characteristic curve analysis showed that the Video Score Questionnaire has a sensitivity of 0.817, a specificity of 0.478, and an efficiency of 65.3. Therefore, the Video Score Questionnaire is reliable and valid for evaluating sarin attacks from brief and unstructured social media videos. Chemical weapons are still used as a method of warfare. Social media videos are an important source of information. We developed a validated scale which can analyse sarin exposure in short and unstructured videos. [ABSTRACT FROM AUTHOR]

Sarin is a highly toxic nerve agent classified by the Chemical Weapon Convention as a Schedule 1 chemical with no use other than to kill or injure. Moreover, in recent times, chemical warfare agents have been deployed against both military and civilian populations. Chemical warfare agents always contain minor impurities that can provide important chemical attribution signatures (CAS) that can aid in forensic investigations. In order to understand the trace molecular composition of sarin, various analytical approaches including GC–MS, LC–MS and NMR were used to determine the chemical markers of a set of sarin samples. Precursor materials were studied and the full characterisation of a synthetic process was undertaken in order to provide new insights into potential chemical attribution signatures for this agent. Several compounds that were identified in the precursor were also found in the sarin samples linking it to its method of preparation. The identification of these CAS contributes critical information about a synthetic route to sarin, and has potential for translation to related nerve agents. [ABSTRACT FROM AUTHOR]

Anxiety disorder is one of the most reported complications following organophosphorus (OP) nerve agent (NA) exposure. The goal of this study was to characterize the long-term behavioral impact of a single low dose exposure to 4-nitrophenyl isopropyl methylphosphonate (NIMP), a sarin surrogate. We chose two different sublethal doses of NIMP, each corresponding to a fraction of the median lethal dose (one mild and one convulsive), and evaluated behavioral changes over a 6-month period following exposure. Mice exposed to both doses showed anxious behavior which persisted for six-months post-exposure. A longitudinal magnetic resonance imaging examination did not reveal any anatomical changes in the amygdala throughout the 6-month period. While no cholinesterase activity change or neuroinflammation could be observed at the latest timepoint in the amygdala of NIMP-exposed mice, important modifications in white blood cell counts were noted, reflecting a perturbation of the systemic immune system. Furthermore, intestinal inflammation and microbiota changes were observed at 6-months in NIMP-exposed animals regardless of the dose received. This is the first study to identify long-term behavioral impairment, systemic homeostasis disorganization and gut microbiota alterations following OP sublethal exposure. Our findings highlight the importance of long-term care for victims of NA exposure, even in asymptomatic cases. [ABSTRACT FROM AUTHOR]

This study proposes a predictive model for assessing adsorber performance in gas purification processes, specifically targeting the removal of chemical warfare agents (CWAs) using breakthrough curve analysis. Conventional parameter estimation methods, such as Brunauer-Emmett-Teller analysis, encounter challenges due to the limited availability of kinetic and equilibrium data for CWAs. To overcome these challenges, we implement a Bayesian parametric inference method, facilitating direct parameter estimation from breakthrough curves. The model's efficacy is confirmed by applying it to H 2 S purification in a fixed-bed setup, where predicted breakthrough curves aligned closely with previous experimental and numerical studies. Furthermore, the model is applied to sarin with ASZM-TEDA carbon, estimating key parameters that could not be assessed through conventional experimental techniques. The reconstructed breakthrough curves closely match actual measurements, highlighting the model's accuracy and robustness. This study not only enhances filter performance prediction for CWAs but also offers a streamlined approach for evaluating gas purification technologies under limited experimental data conditions. [Display omitted] • This study introduces a novel Bayesian model to analyze the gas purification process. • The model accurately estimates elusive adsorption parameters for toxic gas. • The model enables a single-step adsorption analysis using breakthrough curves. • The model's validity is confirmed through a successful application to sarin gas. [ABSTRACT FROM AUTHOR]