The initial sticking of high velocity water onto graphite under non-equilibrium supersonic flow conditions.

In this paper, we present a combined experimental and theoretical study that explored the initial sticking of water on cooled surfaces. Specifically, these ultra-high vacuum gas-surface scattering experiments utilized supersonic molecular beam techniques in conjunction with a cryogenically cooled highly oriented pyrolytic graphite crystal, giving control over incident kinematic conditions. The D2O translational energy spanning 300-750 meV, the relative D2O flux, and the incident angle could all be varied independently. Three different experimental measurements were made. One involved measuring the total amount of D2O scattering as a function of surface temperature to determine the onset of sticking under non-equilibrium gas-surface collision conditions. Another measurement used He specular scattering to assess structural and coverage information for the interface during D2O adsorption. Finally, we used time-of-flight (TOF) measurements of the scattered D2O to determine how energy is exchanged with the graphite surface at surface temperatures above and near the conditions needed for gaseous condensation. For comparison and elaboration of the roles that internal degrees of freedom play in this process, we also did similar TOF measurements using another mass 20 incident particle, atomic neon. Enriching this study are precise molecular dynamics simulations that elaborate on gas-surface energy transfer and the roles of molecular degrees of freedom in gas-surface collisional energy exchange processes. This study furthers our fundamental understanding of energy exchange and the onset of sticking and ultimately gaseous condensation for gas-surface encounters occurring under high-velocity flows.

Atomistic Insight into the Lipid Nanodomains of Synaptic Vesicles.

Membrane curvature, once regarded as a passive consequence of membrane composition and cellular architecture, has been shown to actively modulate various properties of the cellular membrane. These changes could also lead to segregation of the constituents of the membrane, generating nanodomains with precise biological properties. Proteins often linked with neurodegeneration (e.g., tau, alpha-synuclein) exhibit an unintuitive affinity for synaptic vesicles in neurons, which are reported to lack distinct, ordered nanodomains based on their composition. In this study, all-atom molecular dynamics simulations are used to study a full-scale synaptic vesicle of realistic Gaussian curvature and its effect on the membrane dynamics and lipid nanodomain organization. Compelling indicators of nanodomain formation, from the perspective of composition, surface areas per lipid, order parameter, and domain lifetime, are identified in the vesicle membrane, which are absent in a flat bilayer of the same lipid composition. Therefore, our study supports the idea that curvature may induce phase separation in an otherwise fluid, disordered membrane.

Interaction between Permeation Enhancers and Lipid Bilayers.

Permeation enhancers (PEs) are a class of molecules that interact with the epithelial membrane and transiently increase its transcellular permeability. Although there have been few clinical trials of PE coformulated drugs, the mechanism of action of PEs remains elusive. In this paper, the interaction between two archetypes of PEs [salcaprozate sodium (SNAC) and sodium caprate (C10)] and membranes is investigated with extensive all-atom molecular dynamics simulations. The simulations show that (1) the association between the neutral PEs and membranes is favored in free energy, (2) the propensity of neutral PE aggregation is larger in aqueous solution than in lipid bilayers, (3) the equilibrium distribution of neutral PEs in membranes is fast, e.g., accessible with unbiased MD simulations, and (4) the micelle of neutral PEs formed in aqueous solution does not rupture the membranes (e.g., not forming pores or breaking up the membrane) under simulation conditions. All results combined, this study indicates that PEs insert into the membranes in an equilibrium or near equilibrium process. This study lays the foundation for future investigations of how PEs impact the free energy of permeation for small molecules.

Impact of the Unstirred Water Layer on the Permeation of Small-Molecule Drugs.

Over the last two decades, numerous molecular dynamics (MD) simulation-based investigations have attempted to predict the membrane permeability to small-molecule drugs as indicators of their bioavailability, a majority of which utilize the inhomogeneous solubility diffusion (ISD) model. However, MD-based membrane permeability is routinely 3-4 orders of magnitude larger than the values measured with the intestinal perfusion technique. There have been contentious discussions on the sources of the large discrepancies, and the two indisputable, potentially dominant ones are the fixed protonation state of the permeant and the neglect of the unstirred water layer (UWL). Employing six small-molecule drugs of different biopharmaceutical classification system classes, the current MD study relies on the ISD model but introduces the (de)protonation of the permeant by characterizing the permeation free energy of both neutral and charged states. In addition, the role of the UWL as a potential resistance against permeation is explored. The new MD protocol closely mimics the nature of small-molecule permeation and yields estimates that agree well with in vivo intestinal permeability.

Measles: Contemporary considerations for the emergency physician.

Measles, or rubeola, is a highly contagious acute febrile viral illness. Despite the availability of an effective vaccine since 1963, measles outbreaks continue worldwide. This article seeks to provide emergency physicians with the contemporary knowledge required to rapidly diagnose potential measles cases and bolster public health measures to reduce ongoing transmission.

The potential energy profile of the decomposition of 1,1-diamino-2,2-dinitroethylene (FOX-7) in the gas phase.

1,1-Diamino-2,2-dinitroethene (FOX-7) is an energetic material with low sensitivity and high detonation performance, thus it has been considered as a potential replacement for traditional nitro-based energetic materials. In a recent publication (J. Phys. Chem. A, 2022, 126, 4747), the initial decomposition steps of FOX-7 were studied using reflectron time-of-flight mass spectrometry and infrared spectroscopy. The experimental study was complemented with quantum chemistry calculations, which demonstrated the gas phase potential energy surface to be indicative of the reaction process in the condensed phase. The computation in J. Phys. Chem. A, 2022, 126, 4747 focuses on the primary decomposition - but in this manuscript, the full decomposition pathway on the singlet surface, consisting of 54 intermediates and 37 transition states, is characterized at an unprecedented detail. The calculations show that the nitro group, instead of the amine group, is primarily responsible for the sensitivity and endothermicity of FOX-7 decomposition. This result sheds light on how to critically optimize the performance of FOX-7 and design the next generation of nitro-based energetic materials. A comprehensive roadmap, initiated from FOX-7, covers the chemical space of the entire decomposition thus providing a holistic demonstration of various key decomposition pathways leading to various small, gas phase products such as NO, NO2, NH2, CO2, and CO.

Optimized Quantum Phase Estimation for Simulating Electronic States in Various Energy Regimes.

While quantum algorithms for simulations exhibit better asymptotic scaling than their classical counterparts, they currently cannot be accurately implemented on real-world devices. Instead, chemists and computer scientists rely on costly classical simulations of these quantum algorithms. In particular, the quantum phase estimation (QPE) algorithm is among several approaches that has attracted much attention in recent years due to its genuine quantum character. However, it is memory-intensive to simulate and intractable for moderate system sizes. This paper discusses the performance and applicability of QPESIM, a new simulation of the QPE algorithm designed to take advantage of modest computational resources. In particular, we demonstrate the versatility of QPESIM in simulating various electronic states by examining the ground and core-level states of H2O. For these states, we also discuss the effect of the active-space size on the quality of the calculated energies. For the high-energy core-level states, we demonstrate that new QPE simulations for active spaces defined by 15 active orbitals significantly reduce the errors in core-level excitation energies compared to earlier QPE simulations using smaller active spaces.

Charles Bonnet Syndrome With Superimposed Delirium.

Charles Bonnet Syndrome (CBS) is diagnosed when a patient who is psychiatrically intact experiences visual hallucinations in the setting of significant visual acuity or field loss. The exact pathophysiology of the CBS hallucinations remains largely unknown. The main theories include the deafferentation theory and perceptual release theory. There are suspected neurotransmitters involved, including acetylcholine and dopamine. There is no defined treatment protocol with medication for CBS, but various psychotropic medications have been used with varying degrees of remission of symptoms. This case report describes a 64-year-old male with Charles Bonnet Syndrome in the setting of superimposed delirium. We note the different medications that were trialed to reduce his CBS symptoms and decrease episodes of behavioral disturbances. Clinical features of this rare syndrome with superimposed delirium are summarized in hopes of providing directions for management and future study.

Menthol in electronic cigarettes causes biophysical inhibition of pulmonary surfactant.

With an increasing prevalence of electronic cigarette (e-cigarette) use, especially among youth, there is an urgent need to better understand the biological risks and pathophysiology of health conditions related to e-cigarettes. A majority of e-cigarette aerosols are in the submicron size and would deposit in the alveolar region of the lung, where they must first interact with the endogenous pulmonary surfactant. To date, little is known whether e-cigarette aerosols have an adverse impact on the pulmonary surfactant. We have systematically studied the effect of individual e-cigarette ingredients on an animal-derived clinical surfactant preparation, bovine lipid extract surfactant, using a combination of biophysical and analytical techniques, including in vitro biophysical simulations using constrained drop surfactometry, molecular imaging with atomic force microscopy, chemical assays using carbon nuclear magnetic resonance and circular dichroism, and in silico molecular dynamics simulations. All data collectively suggest that flavorings used in e-cigarettes, especially menthol, play a predominant role in inhibiting the biophysical function of the surfactant. The mechanism of biophysical inhibition appears to involve menthol interactions with both phospholipids and hydrophobic proteins of the natural surfactant. These results provide novel insights into the understanding of the health impact of e-cigarettes and may contribute to better regulation of e-cigarette products.

Developing a National Trauma Research Action Plan: Results from the Neurotrauma Research Panel Delphi Survey.

BACKGROUND: In 2016, the National Academies of Science, Engineering and Medicine called for the development of a National Trauma Research Action Plan. The Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma and burn care. Given the public health burden of injuries to the central nervous system, neurotrauma was one of 11 panels formed to address this recommendation with a gap analysis and generation of high-priority research questions. METHODS: We recruited interdisciplinary experts to identify gaps in the neurotrauma literature, generate research questions, and prioritize those questions using a consensus-driven Delphi survey approach. We conducted four Delphi rounds in which participants generated key research questions and then prioritized the importance of the questions on a 9-point Likert scale. Consensus was defined as 60% or greater of panelists agreeing on the priority category. We then coded research questions using an National Trauma Research Action Plan taxonomy of 118 research concepts, which were consistent across all 11 panels. RESULTS: Twenty-eight neurotrauma experts generated 675 research questions. Of these, 364 (53.9%) reached consensus, and 56 were determined to be high priority (15.4%), 303 were deemed to be medium priority (83.2%), and 5 were low priority (1.4%). The research topics were stratified into three groups-severe traumatic brain injury (TBI), mild TBI (mTBI), and spinal cord injury. The number of high-priority questions for each subtopic was 46 for severe TBI (19.7%), 3 for mTBI (4.3%) and 7 for SCI (11.7%). CONCLUSION: This Delphi gap analysis of neurotrauma research identified 56 high-priority research questions. There are clear areas of focus for severe TBI, mTBI, and spinal cord injury that will help guide investigators in future neurotrauma research. Funding agencies should consider these gaps when they prioritize future research. LEVEL OF EVIDENCE: Diagnostic Test or Criteria, Level IV.

Biophysical properties of tear film lipid layer II. Polymorphism of FAHFA.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of endogenous lipids that consist of two acyl chains connected through a single ester bond. Being a unique species of FAHFAs, (O-acyl)-ω-hydroxy fatty acids (OAHFAs) differ from other FAHFAs in that their hydroxy fatty acid backbones are ultralong and their hydroxy esterification is believed to be solely at the terminal (ω-) position. Only in recent years with technological advances in lipidomics have OAHFAs been identified as an important component of the tear film lipid layer (TFLL). It was found that OAHFAs account for approximately 4 mol% of the total lipids and 20 mol% of the polar lipids in the TFLL. However, their biophysical function and contribution to the TFLL is still poorly understood. Here we studied the molecular biophysical mechanisms of OAHFAs using palmitic-acid-9-hydroxy-stearic-acid (PAHSA) as a model. PAHSA and OAHFAs share key structural similarities that could result in comparable biophysical properties and molecular mechanisms. With combined biophysical experiments, atomic force microscopy observations, and all-atom molecular dynamics simulations, we found that the biophysical properties of a dynamic PAHSA monolayer under physiologically relevant conditions depend on a balance between kinetics and thermal relaxation. PAHSA molecules at the air-water surface demonstrate unique polymorphic behaviors, which can be explained by configurational transitions of the molecules under various lateral pressures. These findings could have novel implications in understanding biophysical functions that FAHFAs, in general, or OAHFAs, specifically, play in the TFLL.

Assessing the Intestinal Permeability of Small Molecule Drugs via Diffusion Motion on a Multidimensional Free Energy Surface.

A protocol that accurately assesses the intestinal permeability of small molecule compounds plays an essential role in decreasing the cost and time in inventing a new drug. This manuscript presents a novel computational method to study the passive permeation of small molecule drugs based on the inhomogeneous solubility-diffusion model. The multidimensional free energy surface of the drug transiting through a lipid bilayer is computed with transition-tempered metadynamics that accurately captures the mechanisms of passive permeation. The permeability is computed by following the diffusion motion of the drug molecules along the minimal free energy path found on the multidimensional free energy surface. This computational method is assessed by studying the permeability of five small molecule drugs (ketoprofen, naproxen, metoprolol, propranolol, and salicylic acid). The results demonstrate a remarkable agreement between the computed permeabilities and those measured with the intestinal assay. The in silico method reported in this manuscript also reproduces the permeability measured from the intestinal assay (in vivo) better than the cell-based assays (e.g., PAMPA and Caco-2) do. In addition, the multidimensional free energy surface reveals the interplay between the structure of the small molecule and its permeability, shedding light on strategies of drug optimization.

Penile Dorsal Vein Rupture Identified by Emergency Department Ultrasound.

CASE PRESENTATION: We present the case of a young male with high clinical suspicion of a penile fracture found to have dorsal vein rupture by emergency department point-of-care ultrasound. This false form of penile fracture was subsequently confirmed intraoperatively. DISCUSSION: Penile fracture is a rare clinical entity that may be separated into true vs false penile fracture, with only true fracture requiring surgery. The images submitted here add to the sparse literature evidence that point-of-care ultrasound can be used to differentiate between these two clinical entities. Additionally, this case report highlights an opportunity for further research into and application of point-of-care ultrasound to the evaluation of suspected penile fractures.

Translating COVID-19 knowledge to practice: Enhancing emergency medicine using the "wisdom of crowds".

In the spring of 2020, emergency physicians found themselves in new, uncharted territory as there were few data available for understanding coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In response, knowledge was being crowd sourced and shared across online platforms. The "wisdom of crowds" is an important vehicle for sharing information and expertise. In this article, we explore concepts related to the social psychology of group decisionmaking and knowledge translation. We then analyze a scenario in which the American College of Emergency Physicians (ACEP), a professional medical society, used the wisdom of crowds (via the EngagED platform) to disseminate clinically relevant information and create a useful resource called the "ACEP COVID-19 Field Guide." We also evaluate the crowd-sourced approach, content, and attributes of EngagED compared to other social media platforms. We conclude that professional organizations can play a more prominent role using the wisdom of crowds for augmenting pandemic response efforts.

Molecular Dynamics Study of the Interaction between the N-terminal of α-Synuclein and a Lipid Bilayer Mimicking Synaptic Vesicles.

The interaction between α-synuclein (α-syn) and synaptic vesicles (SVs) plays an important role in the life cycle of α-syn, and a disruption of it could lead to numerous neurodegenerative diseases. The N-terminal of α-syn (first 15 residues) has been shown to recapitulate the association dynamics of α-syn to the bilayer in various studies. This manuscript presents an extensive all-atom molecular dynamics studies (close to 100 µs) of the interaction between the N-terminal of α-syn and a lipid bilayer that mimics the SV under physiological conditions. The research demonstrates α-syn's overwhelming binding preference to the outer leaflet of the SV, which carries a net negative charge as compared to the neutral inner leaflet. Further structural analysis reveals that the Coulombic interaction between the positively charged residues of α-syn and the negatively charged lipid surface is the driving force of the binding, but has a potential of hindering the configurational change of α-syn. In addition, metadynamics simulations are carried out to investigate the folding of the N-terminal of α-syn in the presence and absence of the lipid bilayer, and the result confirms that the α-syn/membrane association facilitates protein folding.

Cardiopulmonary resuscitation and skill retention in emergency physicians.

STUDY OBJECTIVES: The American Heart Association (AHA) recently established the Resuscitation Quality Improvement (RQI) program, which requires physicians to perform quarterly cardiopulmonary resuscitation (CPR) skill checks. The aim of this study was to determine if timing of last training impacted skill performance of emergency physicians. METHODS: A convenience sample of emergency medicine (EM) physicians was asked to complete a Basic Life Support (BLS) scenario on a manikin. Participants passed the scenario if they successfully performed high-quality CPR. Participants completed a survey to assess clinical experience and timing of prior BLS training. Outcomes were comparisons of skills check pass rates for physicians recently trained in BLS (≤90 days) and those trained >90 days ago and those trained >2 years ago. RESULTS: A total of 113 individuals were included in the study: 87 attending physicians and 26 residents. Overall 92.9% correctly performed CPR with the proper assessment, compression rate, compression depth and rescue breaths. There was no difference between success rates in EM physicians who had BLS training within 90 days (91.7%) and physicians who had not had BLS within 90 days, (93.1%). (p = 1.00) There was no difference in the pass rate of those trained within 90 days (91.7%) to those trained >2 years ago (90.9%) (95CI 0.088, 0.096). CONCLUSION: There was no difference between delivery of high-quality CPR in EM physicians who had recent BLS training and those who did not.

Utility of Nonspecific Laboratory Testing for Psychiatric Patients Undergoing Medical Screening in a Military Emergency Department.

INTRODUCTION: Psychiatric complaints account for a sizable and increasing portion of emergency department (ED) visits. Compared with other medical patients, these patients often require substantial resources because of limited specialized resources and prolonged boarding times, which can be detrimental to the safety and satisfaction of other patients. This can prompt early and indiscriminate laboratory testing to expedite early requests for admission consideration. Numerous emergency medicine literature and clinical policies already recommend against indiscriminate screening labs for these patients, yet many psychiatric services require these tests. This study further evidences the limited clinical utility and high associated costs of mandatory protocol screening labs for psychiatric patients evaluated in military EDs. MATERIALS AND METHODS: A retrospective chart review of 441 active duty military patients and their families presenting to Madigan Army Medical Center's ED who received psychiatric diagnoses underwent analysis. A 3-physician review panel evaluated each identified patient case to confirm eligibility and determine whether or not laboratory studies led to a change in patient disposition that was not identified by history, review of systems, physical exam, and known past medical history. The review was approved by the hospital's institutional review board. Contemporary laboratory tests ordered in the evaluation of these patients included complete blood count with differential, complete metabolic panel, thyroid-stimulating hormone, serum ethanol, serum acetaminophen, serum salicylates, urine drug screening, urinalysis, urine human chorionic gonadotropin, and electrocardiograms. RESULTS: Broad screening labs may have altered dispositions for 0.9% (4) of patients. In total, 93% (202) of admitted patients were dispositioned to a psychiatric service. Of the 15 patients admitted to a medical service, 10 involved overdoses or intoxication. One patient had anemia in addition to opioid use disorder as diagnoses and was dispositioned to a medicine service. One pediatric patient was admitted for observation only. The remaining patients had diagnoses based on physical exam and history requiring medical service admission. In total, 7 patients had unknown dispositions, of which 4 carried solely psychiatric diagnoses. CONCLUSIONS: The cumulative reimbursement costs of broad testing in the studied population were estimated at $36,325.17 and rarely altered patient disposition. Further testing does not increase the incidence of disposition altering diagnoses and is associated with increased costs. When individual state laws and the clinical assessment by the responsible emergency physician are considered, future standardized ED lab screening evaluations of psychiatric patients in military EDs may be concentrated to breathalyzer alcohol level, urine drug screen, serum salicylates, serum acetaminophen, and urine human chorionic gonadotropin.

COVID-19 in Seattle-Early lessons learned.

The coronavirus disease 2019 (COVID-19) pandemic has rapidly evolved and now dominates the attention and full efforts of the emergency medicine community, both domestic and abroad. Seattle is the site of the initial diagnosed COVID-19 cases and fatalities in the United States. We provide an overview of the system-level response of 6 Seattle emergency departments and the Washington state chapter of the American College of Emergency Physicians (ACEP) to the COVID-19 pandemic. Local efforts involved the spectrum of emergency response including on- and off-site triage strategies, an approach to personal protective equipment, testing and reporting protocols, early treatments, communication strategies, the impact on front-line providers, and ongoing work.

Immersive Virtual Reality Medical Simulation: Autonomous Trauma Training Simulator.

Background Medical and traumatic emergencies can be intimidating and stressful. This is especially true for early-career medical personnel.Training providers to respond effectively to medical emergencies before being confronted with a real scenario is limited by unnatural or high-cost training modalities that fail to realistically replicate the stress and gravity of real-world trauma management. Immersive virtual reality (IVR) may provide a unique training solution.  Methods We created a working group of 10 active duty or former military emergency medicine physicians and two technical experts. We hosted 10 meetings to facilitate the development process. The program was developed with financial support from the Telemedicine and Advanced Technology Research Center (TATRC), through the primary vendor Exonicus, Inc, with support from Anatomy Next Inc, and Kitware, Inc. Development was completed using an agile project management style, which allowed our team to review progress and provide immediate feedback on previous milestones throughout its completion. The working group completed the resulting four simulation scenarios to evaluate perceived realism and training potential. Finally, testing of the technology platform off the network in a deployed role 3 was conducted. Results Upon completion, we created four IVR scenarios based on the highest mortality battlefield injuries: hemorrhage, tension pneumothorax, and airway obstruction. The working group unanimously indicated a high level of realism and potential training usefulness. Throughout this process, there have been a number of lessons learned and we present those here to show what we have created as well as provide guidance to others creating IVR training solutions.  Conclusion Our team developed trauma scenarios that, to our knowledge, are the only IVR trauma scenarios to run autonomously without instructor input. Furthermore, we provide a potential template for the creation of future autonomous IVR training programs. This framework may offer a dynamic starting point as more teams seek to leverage the capabilities IVR offers.