Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of oximes in KIKO mouse plasma.

Chemical warfare nerve agents (CWNAs) are potent and irreversible inhibitors of acetylcholinesterase (AChE). Oxime reactivators are an important part of the standard treatment for CWNA exposure as they can reactivate inhibited AChE. Evaluating the oxime candidates of interest in biological samples requires analytical detection methods and oxime reactivators as a class of compounds have historically been notoriously difficult to isolate, detect and analyze in an analytical laboratory, and there are currently no sensitive or robust analytical detection methods in the literature.

Topping-Off a Long Thoracic Stabilization With Semi-Rigid Constructs May Have Favorable Biomechanical Effects to Prevent Proximal Junctional Kyphosis: A Biomechanical Comparison.

Study Design: In-vitro cadaveric biomechanical study.

Objectives: Long posterior spinal fusion is a standard treatment for adult spinal deformity. However, these rigid constructs are known to alter motion and stress to the adjacent non-instrumented vertebrae, increasing the risk of proximal junctional kyphosis (PJK).

Effects of Supplemental Diet during Breeding on Fertility, Litter Size, Survival Rate, and Weaning Weight in Mice ().

The addition of supplemental diets to laboratory animals, specifically rodents, is a common practice for the provision of additional nutritional support. We set out to investigate whether the use of commercially available supplemental diets during breeding affected fertility rate, litter size, pup health, and pup survival. Genetically modified female breeding mice with a C57BL/6 background were divided into 3 groups ( = 16 per group) that received standard rodent chow alone or standard rodent chow with one of 2 commercially available supplemental diets: Love Mash (Bio-Serv) extruded pellet or Nutra-Gel (Bio-Serv) diet gel.

Treatment of Organophosphorus Poisoning with 6-Alkoxypyridin-3-ol Quinone Methide Precursors: Resurrection of Methylphosphonate-Aged Acetylcholinesterase.

Organophosphorus (OP) nerve agents inhibit acetylcholinesterase (AChE), creating a cholinergic crisis in which death can occur. The phosphylated serine residue spontaneously dealkylates to the OP-aged form, which current therapeutics cannot reverse. Soman's aging half-life is 4.

Volumetric Modulated Arc Therapy Craniospinal Irradiation Utilizing a Vertebral Body Sparing Approach: An Alternative Approach to Improve Access and Minimize Toxicity.

Introduction: Craniospinal irradiation (CSI) is indicated for adult patients diagnosed with leptomeningeal disease (LMD). Proton-based vertebral body sparing (VBS) CSI has been explored with pediatric patients to minimize hematologic toxicity; however, utilization of VBS in an adult population is limited. A recent phase II trial has shown efficacy of proton-based CSI to treat non-small cell lung and breast cancer with LMD.

The role of stigma in cannabis use disclosure: an exploratory study.

Background: Although cannabis use incidence, societal acceptance, and legislation all trend positively, cannabis remains federally illegal in the USA. Prior studies have revealed that patients are reluctant to disclose their cannabis use history in the healthcare system, which can negatively impact patient care. This study reports the frequency of cannabis use disclosure with special considerations for stigmatization.

Patient and Caregiver Perspectives on Care-Seeking During a Vaso-Occlusive Crisis in Sickle Cell Disease: Results from Qualitative Interviews in Canada.

Purpose: There is little research on care-seeking preferences during active pain crises for sickle cell disease (SCD) patients and their caregivers. The objective of this study was to identify relevant, patient or caregiver narratives of the pain crisis experience, to understand the factors that contribute to care-seeking during a pain crisis, and to identify preferences when making care-seeking decisions during a pain crisis.

Patients And Methods: Qualitative semi-structured interviews were conducted with Canadian residents with a self-reported SCD diagnosis, who were either ≥18 years of age or an adolescent between the ages of 12-18.

Radiation Therapy Without Anesthesia for a 2-Year-Old Child Using Audio-Visual Assisted Therapeutic Ambience in Radiation Therapy (AVATAR).

Purpose: Radiation therapy (RT) is essential to managing many pediatric malignancies but can provoke anxiety, fear, and discomfort for children owing to prolonged treatment time, extended course, and restrictive immobilization. Patients younger than 10 years frequently require daily general anesthesia (GA), which is resource intensive, expensive, potentially toxic, and anxiety and fear provoking. Audio-Visual Assisted Therapeutic Ambience in Radiation Therapy (AVATAR), a video streaming device, has been proposed as an alternative to anesthesia in patients aged 3 to 10 years.

Development of a CNS-permeable reactivator for nerve agent exposure: an iterative, multi-disciplinary approach.

Nerve agents have experienced a resurgence in recent times with their use against civilian targets during the attacks in Syria (2012), the poisoning of Sergei and Yulia Skripal in the United Kingdom (2018) and Alexei Navalny in Russia (2020), strongly renewing the importance of antidote development against these lethal substances. The current standard treatment against their effects relies on the use of small molecule-based oximes that can efficiently restore acetylcholinesterase (AChE) activity. Despite their efficacy in reactivating AChE, the action of drugs like 2-pralidoxime (2-PAM) is primarily limited to the peripheral nervous system (PNS) and, thus, provides no significant protection to the central nervous system (CNS).

Novel Genetically Modified Mouse Model to Assess Soman-Induced Toxicity and Medical Countermeasure Efficacy: Human Acetylcholinesterase Knock-in Serum Carboxylesterase Knockout Mice.

The identification of improved medical countermeasures against exposure to chemical warfare nerve agents (CWNAs), a class of organophosphorus compounds, is dependent on the choice of animal model used in preclinical studies. CWNAs bind to acetylcholinesterase and prevent the catalysis of acetylcholine, causing a plethora of peripheral and central physiologic manifestations, including seizure. Rodents are widely used to elucidate the effects of CWNA-induced seizure, albeit with a caveat: they express carboxylesterase activity in plasma.

Who Are We Missing? The Impact of Requiring Parental or Guardian Consent on Research With Lesbian, Gay, Bisexual, Trans, Two-Spirit, Queer/Questioning Youth.

Purpose: The purpose was to examine whether a requirement for parental or guardian consent systematically limits which lesbian, gay, bisexual, trans, two-spirit, queer/questioning (LGBT2Q+) youth participate in research.

Methods: A total of 60 LGBT2Q+ youth (aged 14-18 years) completed measures assessing gender and sexual minority identity, depression and anxiety, help-seeking intentions, and social support.

Results: A substantial proportion (37.

Adeno-associated virus-mediated expression of human butyrylcholinesterase to treat organophosphate poisoning.

Rare diseases defined by genetic mutations are classic targets for gene therapy. More recently, researchers expanded the use of gene therapy in non-clinical studies to infectious diseases through the delivery of vectorized antibodies to well-defined antigens. Here, we further extend the utility of gene therapy beyond the "accepted" indications to include organophosphate poisoning.

Butyrylcholinesterase, a stereospecific in vivo bioscavenger against nerve agent intoxication.

Human butyrylcholinesterase (E.C. 3.

Nanoscavenger provides long-term prophylactic protection against nerve agents in rodents.

Nerve agents are a class of organophosphorus compounds (OPs) that blocks communication between nerves and organs. Because of their acute neurotoxicity, it is extremely difficult to rescue the victims after exposure. Numerous efforts have been devoted to search for an effective prophylactic nerve agent bioscavenger to prevent the deleterious effects of these compounds.

Assessment of mouse strain differences in baseline esterase activities and toxic response to sarin.

Genetics likely play a role in various responses to nerve agent (NA) exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses. This study uses different mouse strains to identify if mouse strain differences in sarin exposure exist. In Experiment 1, basal levels of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase (CE) were measured in different strains of naïve mice to account for potential pharmacokinetic determinants of individual differences.

Evaluating mice lacking serum carboxylesterase as a behavioral model for nerve agent intoxication.

Mice and other rodents are typically utilized for chemical warfare nerve agent research. Rodents have large amounts of carboxylesterase in their blood, while humans do not. Carboxylesterase nonspecifically binds to and detoxifies nerve agent.

Managing emotionally charged conversations between faculty and residents: a skill-building workshop.

This article was migrated. The article was marked as recommended. Discussions with residents regarding remediation, probation, or dismissal are challenging, but only limited practical guidance about constructive conversations is available.

Purification, characterization, and N-glycosylation of recombinant butyrylcholinesterase from transgenic rice cell suspension cultures.

Recombinant butyrylcholinesterase produced in a metabolically regulated transgenic rice cell culture (rrBChE) was purified to produce a highly pure (95%), active form of enzyme. The developed downstream process uses common manufacturing friendly operations including tangential flow filtration, anion-exchange chromatography, and affinity chromatography to obtain a process recovery of 42% active rrBChE. The purified rrBChE was then characterized to confirm its comparability to the native human form of the molecule (hBChE).

The role of genetic background in susceptibility to chemical warfare nerve agents across rodent and non-human primate models.

Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies.

Risks of secondary malignancies with heterotopic bone radiation therapy for patients younger than 40 years.

Heterotopic ossification (HO) of the bone is defined as a benign condition in which abnormal bone formation occurs in soft tissue. One of the most common prophylactic treatments for HO is radiation therapy (RT). This study retrospectively reviewed 20 patients younger than the age of 40 who received radiation to prevent HO in a single fraction of 7 Gray.

Probing the activity of a non-oxime reactivator for acetylcholinesterase inhibited by organophosphorus nerve agents.

Currently fielded treatments for nerve agent intoxication include atropine, an acetylcholine receptor antagonist, and pralidoxime (2PAM), a small molecule reactivator of acetylcholinesterase (AChE). 2PAM reactivates nerve agent-inhibited AChE via direct nucleophilic attack by the oxime moiety on the phosphorus center of the bound nerve agent. Due to a permanently charged pyridinium motif, 2PAM is not thought to cross the blood brain barrier and therefore cannot act directly in the neuronal junctions of the brain.