A Novel Flp Reporter Mouse Shows That TRPA1 Expression Is Largely Limited to Sensory Neuron Subsets.

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal cation channel that is activated by electrophilic irritants, oxidative stress, cold temperature, and GPCR signaling. TRPA1 expression has been primarily identified in subsets of nociceptive sensory afferents and is considered a target for future analgesics. Nevertheless, TRPA1 has been implicated in other cell types including keratinocytes, epithelium, enterochromaffin cells, endothelium, astrocytes, and CNS neurons.

Xenobiotic Exposure and Migraine-Associated Signaling: A Multimethod Experimental Study Exploring Cellular Assays in Combination with and Mouse Models.

Background: Mechanisms for how environmental chemicals might influence pain has received little attention. Epidemiological studies suggest that environmental factors such as pollutants might play a role in migraine prevalence. Potential targets for pollutants are the transient receptor potential (TRP) channels ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1), which on activation release pain-inducing neuropeptide calcitonin gene-related peptide (CGRP).

Action potential conduction in the mouse and rat vagus nerve is dependent on multiple voltage-gated sodium channels (Na1s).

Action potential (AP) conduction depends on voltage-gated sodium channels, of which there are nine subtypes. The vagus nerve, comprising sensory afferent fibers and efferent parasympathetic fibers, provides autonomic regulation of visceral organs, but the voltage-gated sodium channels (Na1) subtypes involved in its AP conduction are poorly defined. We studied the A- and C-waves of electrically stimulated compound action potentials (CAPs) of the mouse and rat vagus nerves with and without Na1 inhibitor administration: tetrodotoxin (TTX), PF-05089771 (mouse Na1.

Irritant-evoked reflex tachyarrhythmia in spontaneously hypertensive rats is reduced by inhalation of TRPM8 agonists l-menthol and WS-12.

Inhalation of noxious irritants activates nociceptive sensory afferent nerves innervating the airways, inducing reflex regulation of autonomic networks and the modulation of respiratory drive and cardiovascular (CV) parameters such as heart rate and blood pressure. In healthy mammals, irritant-evoked pulmonary-cardiac reflexes cause parasympathetic-mediated bradycardia. However, in spontaneously hypertensive (SH) rats, irritant inhalation also increases sympathetic drive to the heart.

Neural control of the lower airways: Role in cough and airway inflammatory disease.

Airway function is under constant neurophysiological control, in order to maximize airflow and gas exchange and to protect the airways from aspiration, damage, and infection. There are multiple sensory nerve subtypes, whose disparate functions provide a wide array of sensory information into the CNS. Activation of these subtypes triggers specific reflexes, including cough and alterations in autonomic efferent control of airway smooth muscle, secretory cells, and vasculature.

Comparing the Nurse Work Environment, Job Satisfaction, and Intent to Leave Among Military, Magnet®, Magnet-Aspiring, and Non-Magnet Civilian Hospitals.

Objective: This study aimed to compare the nurse work environment, job satisfaction, and intent to leave (ITL) among military, Magnet®, Magnet-aspiring, and non-Magnet civilian hospitals.

Background: The professional nurse work environment is an important, modifiable, organizational trait associated with positive nurse and patient outcomes; creating and maintaining a favorable work environment should be imperative for nursing leaders.

Methods: Secondary data from the Army Nurse Corps and the National Database of Nursing Quality Indicators included the Practice Environment Scale of the Nursing Work Index (PES-NWI) and single-item measures of job satisfaction and ITL.

Research Opportunities in Autonomic Neural Mechanisms of Cardiopulmonary Regulation: A Report From the National Heart, Lung, and Blood Institute and the National Institutes of Health Office of the Director Workshop.

This virtual workshop was convened by the National Heart, Lung, and Blood Institute, in partnership with the Office of Strategic Coordination of the Office of the National Institutes of Health Director, and held September 2 to 3, 2020. The intent was to assemble a multidisciplinary group of experts in basic, translational, and clinical research in neuroscience and cardiopulmonary disorders to identify knowledge gaps, guide future research efforts, and foster multidisciplinary collaborations pertaining to autonomic neural mechanisms of cardiopulmonary regulation. The group critically evaluated the current state of knowledge of the roles that the autonomic nervous system plays in regulation of cardiopulmonary function in health and in pathophysiology of arrhythmias, heart failure, sleep and circadian dysfunction, and breathing disorders.

Mapping of the Sensory Innervation of the Mouse Lung by Specific Vagal and Dorsal Root Ganglion Neuronal Subsets.

The airways are densely innervated by sensory afferent nerves, whose activation regulates respiration and triggers defensive reflexes (e.g., cough, bronchospasm).

Predictors of Temporary Profile Days Among U.S. Army Active Duty Soldiers.

Introduction: More than 40,000 soldiers cannot deploy every year, which undermines readiness. The medical readiness of soldiers is a critical component of the overall operational readiness of the U.S.

Identifying Potentially Preventable Reasons Nurses Intend to Leave a Job.

Objective: The aim of this study was to describe the relationships between intent to leave, reasons nurses intend to leave, and the nursing work environment in military hospitals.

Background: Intention to leave is a precursor of nurse turnover. The reasons nurses intend to leave may be influenced by leader interventions and potentially preventable.

Patient Vs. Soldier-Centered Medical Home: Comparing Access, Continuity, and Communication in the U.S. Army.

Introduction: Over the last 40 years, patient-centered medical home (PCMH) has evolved as the leading primary care practice model, replacing traditional primary care models in the United States and internationally. The goal of PCMH is to improve chronic condition management. In the U.

The Value of the Patient-Centered Medical Home in Getting Adults Suffering From Acute Conditions Back to Work: An Integrative Literature Review.

Acute conditions are the leading cause of work restrictions and missed workdays, contributing to over $27 billion in lost productivity each year and negatively impacting workers' health and quality of life. Primary care services, specifically patient-centered medical homes (PCMHs), play an essential role in supporting timely acute illness or injury recovery for working adults. The purpose of this review is to synthesize the evidence on the relationship between PCMH implementation, care processes, and outcomes.

Contribution of tetrodotoxin-sensitive, voltage-gated sodium channels (Na1) to action potential discharge from mouse esophageal tension mechanoreceptors.

Action potentials depend on voltage-gated sodium channels (Na1s), which have nine α subtypes. Na1 inhibition is a target for pathologies involving excitable cells such as pain. However, because Na1 subtypes are widely expressed, inhibitors may inhibit regulatory sensory systems.

Irritant Inhalation Evokes P Wave Morphological Changes in Spontaneously Hypertensive Rats via Reflex Modulation of the Autonomic Nervous System.

Irritant inhalation is associated with increased incidence of atrial fibrillation (AF) and stroke. Irritant inhalation acutely regulates cardiac function via autonomic reflexes. Increases in parasympathetic and sympathetic reflexes may increase atrial susceptibility to ectopic activity and the initiation of arrhythmia such as AF.

Functional evidence of distinct electrophile-induced activation states of the ion channel TRPA1.

Transient Receptor Potential Ankyrin 1 (TRPA1) is a tetrameric, nonselective cation channel expressed on nociceptive sensory nerves whose activation elicits nocifensive responses (e.g. pain).

Differential sensitivity of cinnamaldehyde-evoked calcium fluxes to ruthenium red in guinea pig and mouse trigeminal sensory neurons.

Objective: Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel expressed on a subset of sensory neurons. TRPA1 is activated by a host of noxious stimuli including pollutants, irritants, oxidative stress and inflammation, and is thought to play an important role in nociception and pain perception. TRPA1 is therefore a therapeutic target for diseases with nociceptive sensory signaling components.

Molecular identity, anatomy, gene expression and function of neural crest vs. placode-derived nociceptors in the lower airways.

The lower airways (larynx to alveoli) are protected by a complex array of neural networks that regulate respiration and airway function. Harmful stimuli trigger defensive responses such as apnea, cough and bronchospasm by activating a subpopulation of sensory afferent nerves (termed nociceptors) which are found throughout the airways. Airway nociceptive fibers are projected from the nodose vagal ganglia, the jugular vagal ganglia and the dorsal root ganglia, which are derived from distinct embryological sources: the former from the epibranchial placodes, the latter two from the neural crest.

Air Pollution-Induced Autonomic Modulation.

Air pollutants pose a serious worldwide health hazard, causing respiratory and cardiovascular morbidity and mortality. Pollutants perturb the autonomic nervous system, whose function is critical to cardiopulmonary homeostasis. Recent studies suggest that pollutants can stimulate defensive sensory nerves within the cardiopulmonary system, thus providing a possible mechanism for pollutant-induced autonomic dysfunction.

Aldosterone up-regulates voltage-gated potassium currents and NKCC1 protein membrane fractions.

Na-K-2Cl Cotransporter (NKCC1) is a protein that aids in the active transport of sodium, potassium, and chloride ions across cell membranes. It has been shown that long-term systemic treatment with aldosterone (ALD) can enhance NKCC1 protein expression and activity in the aging cochlea resulting in improved hearing. In the present work, we used a cell line with confirmed NKCC1 expression to demonstrate that in vitro application of ALD increased outward voltage-gated potassium currents significantly, and simultaneously upregulated whole lysate and membrane portion NKCC1 protein expression.

Development of a Mouse Reporter Strain for the Purinergic P2X Receptor.

The ATP-sensitive P2X ionotropic receptor plays a critical role in a number of signal processes including taste and hearing, carotid body detection of hypoxia, the exercise pressor reflex and sensory transduction of mechanical stimuli in the airways and bladder. Elucidation of the role of P2X has been hindered by the lack of selective tools. In particular, detection of P2X using established pharmacological and biochemical techniques yields dramatically different expression patterns, particularly in the peripheral and central nervous systems.

Antimycin A increases bronchopulmonary C-fiber excitability via protein kinase C alpha.

Inflammation can increase the excitability of bronchopulmonary C-fibers leading to excessive sensations and reflexes (e.g. wheeze and cough).

Mapping of Sensory Nerve Subsets within the Vagal Ganglia and the Brainstem Using Reporter Mice for Pirt, TRPV1, 5-HT3, and Tac1 Expression.

Vagal afferent sensory nerves, originating in jugular and nodose ganglia, are composed of functionally distinct subsets whose activation evokes distinct thoracic and abdominal reflex responses. We used Cre-expressing mouse strains to identify specific vagal afferent populations and map their central projections within the brainstem. We show that Pirt is expressed in virtually all vagal afferents; whereas, 5-HT3 is expressed only in nodose neurons, with little expression in jugular neurons.

Soldier-Centered Care: A Concept Analysis.

Introduction: It is critical for the U.S. Army Medical Department to acknowledge the distinctive medical needs of soldiers and conceptualize soldier-centered care as a unique concept.