Search NASA⌕ Search

SEARCH · Search NASA

Results for “Addiction”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

35 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Mechanisms of QT prolongation by buprenorphine cannot be explained by direct hERG channel block

Buprenorphine is a μ-opioid receptor (MOR) partial agonist used to manage pain and addiction. QT C prolongation that crosses the 10 msec threshold of regulatory concern was observed at a supratherapeutic dose in two thorough QT studies for the transdermal buprenorphine product BUTRANS®. Because QT C prolongation can be associated with Torsades de Pointes (TdP), a rare but potentially fatal ventricular arrhythmia, these results have led to further investigation of the electrophysiological effects of buprenorphine. Drug-induced QT C prolongation and TdP are most commonly caused by acute inhibition of hERG current (I hERG ) that contribute to the repolarizing phase of the ventricular action potentials (APs). Concomitant inhibition of inward late Na + (I NaL ) and/or L-type Ca 2+ (I CaL ) current can offer some protection against proarrhythmia. Therefore, we characterized the effects of buprenorphine and its major metabolite norbuprenorphine on cardiac hERG, Ca 2+ , and Na + ion channels, as well as cardiac APs. For comparison, methadone, a MOR agonist associated with QT C prolongation and high TdP risk, and naltrexone and naloxone, two opioid receptor antagonists, were also studied. Whole cell recordings were performed at 37°C on cells stably expressing hERG, Ca V 1.2, and Na V 1.5 proteins. Microelectrode array (MEA) recordings were made on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The results showed that buprenorphine, norbuprenorphine, naltrexone, and naloxone had no effect on I hERG , I CaL , I NaL , and peak Na + current (I NaP ) at clinically relevant concentrations. In contrast, methadone inhibited I hERG , I CaL , and I NaL . Experiments on iPSC-CMs showed a lack of effect for buprenorphine, norbuprenorphine, naltrexone, and naloxone, and delayed repolarization for methadone at clinically relevant concentrations. The mechanism of QT C prolongation is opioid moiety-specific. This remains undefined for buprenorphine, while for methadone it involves direct hERG channel block. There is no evidence that buprenorphine use is associated with TdP. Whether this lack of TdP risk can be generalized to other drugs with QT C prolongation not mediated by acute hERG channel block warrants further study.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Unbalancing Symbiotic Nitrogen Fixation: Can We Make Effectiveness More Effective?

One of the most critical uses of carbon fuels is in generating nitrogen fertilizer. Atmospheric dinitrogen is too stable to be used directly by plants, so plants need other chemical forms of nitrogen. Nitrogen fertilizer production uses ~4% of the world’s natural gas. Making N fertilizers leverages methane’s energy content by enabling additional energy to be captured into food and fiber through increased photosynthesis. Manufacturing fertilizer is essential—without it there would only be enough combined nitrogen to feed ~3 billion of the world’s ~7 billion people. How to alter this addiction is not obvious, but the best chance to secure substantial and sustainable amounts of future N might be through symbiotic nitrogen fixation (SNF). SNF describes mutualistic interactions where nitrogen-fixing bacteria provide fixed nitrogen to their plant hosts, freeing them from the need for nitrogen fertilizers. SNF already occurs on a large scale; "biological nitrogen” contributes about 5 Tg N/yr to American agriculture, a quarter of the nitrogen needed. Improving SNF and replacing inorganic fertilizers are both important goals in establishing sustainable and more energy-efficient farming. SNF has been used in agriculture for millennia, largely by using legumes like beans or alfalfa in mixed cropping systems. Legume SNF occurs in root nodules, organs that develop after a growing root is infected by bacteria called rhizobia. In the plant cells of a legume nodule, specialized forms of rhizobia fix nitrogen and can produce enough ammonia to supply the growing plant. The exchange of photosynthetically derived plant carbon compounds for nitrogen reduced by the bacteria is the engine that drives the symbiosis. Important details about the organization of development and metabolism in SNF remain to be determined, such as how plant and bacterial metabolism are coordinated as nitrogen is being fixed and what governs the overall level of nitrogen fixation. Most bacterial mutations that affect SNF completely block fixation (e.g. are Fix – ), providing a limited window into the feedback interactions that must be part of the process. We have investigated an unusual mutant of Sinorhizobium meliloti, a symbiotic partner of alfalfa, that fixes dinitrogen at a normal rate (i.e., it is Fix + ) but is not effective in supporting plant growth (i.e., it is ineffective or Eff – ). We have shown that the mutant has a specific mutation in the glnD gene, which codes for a protein that regulates the bacterial response to nitrogen stress, among other key pathways. A Fix + Eff – phenotype contains an unavoidable puzzle—how is it possible for the bacteria to fix nitrogen at a normal rate and without benefiting the nitrogen starved plant host? After eliminating other possibilities, we proposed that the bacteria synthesize a nitrogen-containing compound that the plant can’t use so that acquiring this compound does not relieve plant nitrogen stress. Extracts of nodules made by glnD mutant strains have high concentrations of pyruvate canaline oxime (PCO), a derivative of the plant defensive compound canaline, a toxic analog of ornithine, an amino acid. Many legumes produce canaline and the related arginine mimic canavanine. For reasons we do not yet understand, the mutation in glnD appears to trigger significant overproduction of canaline in a defense response that leads to substantial synthesis of PCO. We expected the bacteria to be able to use PCO, but we have not been able to grow S. meliloti on PCO under several conditions. PCO thus appears to be a metabolic dead end for both the plant and bacteria. We also examined bacterial catabolic pathways that degrade arginine and canavanine and showed that mutation of these did not alter the symbiosis in an obvious way. In related experiments to examine the metabolic development of root nodules, we carried out an ambitious experiment to simultaneously measure metabolites and protein changes during nodule maturation. For these experiments we used a related symbiotic interaction between S. medicae and Medicago truncatula. M. truncatula has a simpler genome than alfalfa so we could identify plant proteins based on predictions from the DNA sequence. Nodules formed on Medicago grow linearly, with the least mature tissues at the tip. Because development of nitrogen fixation is accompanied by the production of the pigmented plant oxygen carrier protein leghemoglobin, we were able to locate and manually separate the tip, transitional, and mature nitrogen-fixing regions from each other. Advances in proteomic and metabolomic techniques allowed us to analyze these tissues from a pool of as few as 10 nodules. We observed correlated transitions of various enzymes in the plant and bacterial proteomes from those characteristic of free-living metabolism to the microaerobic metabolism of the nitrogen-fixing tissues. The metabolome could not be separated into plant and bacterial domains but was consistent with this overall transition. A subsequent paper examined proteolysis in nodule bacteria. Protein turnover in mature regions of the nodule is significant. We were able to show complexes between various proteins and important proteases, using precipitation capture techniques to isolate the proteases and sensitive proteomic analysis to reveal the associated proteins.

09 BIOMASS FUELS↗
DOE OSTI2023

Persistence Control of Engineered Functions in Complex Soil Microbiomes (PerCon SFA), Secure Biosystems Design Project Data Catalog at PNNL DataHub

The Persistence Control of Engineered Functions in Complex Soil Microbiomes Project (PerCon SFA) at Pacific Northwest National Laboratory (PNNL) is a Genomic Sciences Program Biosystems Design, Science Focus Area research project consortium. Collaborating across highly integrated institutions, PerCon SFA scientists are exploring how environmental niches can be sculpted using the mechanisms of genome reduction and metabolic addiction to drive secure rhizosphere community design for robust biomass cropping in challenging environments. The PerCon SFA DataHub project repository contains publication-relevant digital dataset and metadata DOI packages, enabling exploration and download of integrated experimental dataset catalogs publicly available to a global scientific community. and metadata repository allow for exploring and downloading integrated experimental biodesign omics dataset catalogs, including experimental protocols and/or workflows, raw and/or processed data, as required by the repository, and other relevant supporting materials and/or metadata required for research reproducibility and reporting.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Dose-dependent consequences of sub-chronic fentanyl exposure on neuron and glial co-cultures

Fentanyl is one of the most common opioid analgesics administered to patients undergoing surgery or for chronic pain management. While the side effects of chronic fentanyl abuse are recognized (e.g., addiction, tolerance, impairment of cognitive functions, and inhibit nociception, arousal, and respiration), it remains poorly understood what and how changes in brain activity from chronic fentanyl use influences the respective behavioral outcome. Here, we examined the functional and molecular changes to cortical neural network activity following sub-chronic exposure to two fentanyl concentrations, a low (0.01 μM) and high (10 μM) dose. Primary rat co-cultures, containing cortical neurons, astrocytes, and oligodendrocyte precursor cells, were seeded in wells on either a 6-well multi-electrode array (MEA, for electrophysiology) or a 96-well tissue culture plate (for serial endpoint bulk RNA sequencing analysis). Once networks matured (at 28 days in vitro ), co-cultures were treated with 0.01 or 10 μM of fentanyl for 4 days and monitored daily. Only high dose exposure to fentanyl resulted in a decline in features of spiking and bursting activity as early as 30 min post-exposure and sustained for 4 days in cultures. Transcriptomic analysis of the complex cultures after 4 days of fentanyl exposure revealed that both the low and high dose induced gene expression changes involved in synaptic transmission, inflammation, and organization of the extracellular matrix. Collectively, the findings of this in vitro study suggest that while neuroadaptive changes to neural network activity at a systems level was detected only at the high dose of fentanyl, transcriptomic changes were also detected at the low dose conditions, suggesting that fentanyl rapidly elicits changes in plasticity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor

The United States is experiencing the most profound and devastating opioid crisis in history, with the number of deaths involving opioids, including prescription and illegal opioids, continuing to climb over the past two decades. This severe public health issue is difficult to combat as opioids remain a crucial treatment for pain, and at the same time, they are also highly addictive. Opioids act on the opioid receptor, which in turn activates its downstream signaling pathway that eventually leads to an analgesic effect. Among the four types of opioid receptors, the µ subtype is primarily responsible for the analgesic cascade. This review describes available 3D structures of the µ opioid receptor in the protein data bank and provides structural insights for the binding of agonists and antagonists to the receptor. Comparative analysis on the atomic details of the binding site in these structures was conducted and distinct binding interactions for agonists, partial agonists, and antagonists were observed. The findings in this article deepen our understanding of the ligand binding activity and shed some light on the development of novel opioid analgesics which may improve the risk benefit balance of existing opioids.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine

Dopaminergic (DA) neurons exert profound influences on behavior including addiction. However, how DA axons communicate with target neurons and how those communications change with drug exposure remains poorly understood. We leverage cell type-specific labeling with large volume serial electron microscopy to detail DA connections in the nucleus accumbens (NAc) of the mouse (Mus musculus) before and after exposure to cocaine. We find that individual DA axons contain different varicosity types based on their vesicle contents. Spatially ordering along individual axons further suggests that varicosity types are non-randomly organized. DA axon varicosities rarely make specific synapses (<2%, 6/410), but instead are more likely to form spinule-like structures (15%, 61/410) with neighboring neurons. Days after a brief exposure to cocaine, DA axons were extensively branched relative to controls, formed blind-ended ‘bulbs’ filled with mitochondria, and were surrounded by elaborated glia. Finally, mitochondrial lengths increased by ~2.2 times relative to control only in DA axons and NAc spiny dendrites after cocaine exposure. We conclude that DA axonal transmission is unlikely to be mediated via classical synapses in the NAc and that the major locus of anatomical plasticity of DA circuits after exposure to cocaine are large-scale axonal re-arrangements with correlated changes in mitochondria.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1998

Perspective on the impact of weightlessness on calcium and bone metabolism

As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

short duration↗
NASA NTRS2011

Reducing US Oil Dependence Using Simulation

People across the world are addicted to oil; as a result, the instability of oil prices and the shortage of oil reserves have influenced human behaviors and global businesses. Today, the United States makes up only 5% of the global population but consumes 25% of the. world total energy. Most of this energy is generated from fossil fuels in the form of electricity. The contribution of this paper is to examine the possibilities of replacing fossil fuel with renewable energies to generate electricity as well as to examine other methods to reduce oil and gas consumption. We propose a system dynamics model in an attempt to predict the future US dependence on fossil fuels by using renewable energy resources such as, nuclear, wind, solar, and hydro powers. Based on the findings of our model, the study expects to provide insights towards promising solutions of the oil dependency problem.

Ayoub, Fadi↗
NASA NTRS2012

Spinoff 2011

Topics include: Bioreactors Drive Advances in Tissue Engineering; Tooling Techniques Enhance Medical Imaging; Ventilator Technologies Sustain Critically Injured Patients; Protein Innovations Advance Drug Treatments, Skin Care; Mass Analyzers Facilitate Research on Addiction; Frameworks Coordinate Scientific Data Management; Cameras Improve Navigation for Pilots, Drivers; Integrated Design Tools Reduce Risk, Cost; Advisory Systems Save Time, Fuel for Airlines; Modeling Programs Increase Aircraft Design Safety; Fly-by-Wire Systems Enable Safer, More Efficient Flight; Modified Fittings Enhance Industrial Safety; Simulation Tools Model Icing for Aircraft Design; Information Systems Coordinate Emergency Management; Imaging Systems Provide Maps for U.S. Soldiers; High-Pressure Systems Suppress Fires in Seconds; Alloy-Enhanced Fans Maintain Fresh Air in Tunnels; Control Algorithms Charge Batteries Faster; Software Programs Derive Measurements from Photographs; Retrofits Convert Gas Vehicles into Hybrids; NASA Missions Inspire Online Video Games; Monitors Track Vital Signs for Fitness and Safety; Thermal Components Boost Performance of HVAC Systems; World Wind Tools Reveal Environmental Change; Analyzers Measure Greenhouse Gasses, Airborne Pollutants; Remediation Technologies Eliminate Contaminants; Receivers Gather Data for Climate, Weather Prediction; Coating Processes Boost Performance of Solar Cells; Analyzers Provide Water Security in Space and on Earth; Catalyst Substrates Remove Contaminants, Produce Fuel; Rocket Engine Innovations Advance Clean Energy; Technologies Render Views of Earth for Virtual Navigation; Content Platforms Meet Data Storage, Retrieval Needs; Tools Ensure Reliability of Critical Software; Electronic Handbooks Simplify Process Management; Software Innovations Speed Scientific Computing; Controller Chips Preserve Microprocessor Function; Nanotube Production Devices Expand Research Capabilities; Custom Machines Advance Composite Manufacturing; Polyimide Foams Offer Superior Insulation; Beam Steering Devices Reduce Payload Weight; Models Support Energy-Saving Microwave Technologies; Materials Advance Chemical Propulsion Technology; and High-Temperature Coatings Offer Energy Savings.

Source record↗
NASA NTRS2012

Test Driven Development of Scientific Models

Test-Driven Development (TDD) is a software development process that promises many advantages for developer productivity and has become widely accepted among professional software engineers. As the name suggests, TDD practitioners alternate between writing short automated tests and producing code that passes those tests. Although this overly simplified description will undoubtedly sound prohibitively burdensome to many uninitiated developers, the advent of powerful unit-testing frameworks greatly reduces the effort required to produce and routinely execute suites of tests. By testimony, many developers find TDD to be addicting after only a few days of exposure, and find it unthinkable to return to previous practices. Of course, scientific/technical software differs from other software categories in a number of important respects, but I nonetheless believe that TDD is quite applicable to the development of such software and has the potential to significantly improve programmer productivity and code quality within the scientific community. After a detailed introduction to TDD, I will present the experience within the Software Systems Support Office (SSSO) in applying the technique to various scientific applications. This discussion will emphasize the various direct and indirect benefits as well as some of the difficulties and limitations of the methodology. I will conclude with a brief description of pFUnit, a unit testing framework I co-developed to support test-driven development of parallel Fortran applications.

Clune, Thomas L.↗
NASA NTRS2012

On the Transition and Migration of Flight Functions in the Airspace System

Since ~400 BC, when man first replicated flying behavior with kites, up until the turn of the 20th century, when the Wright brothers performed the first successful powered human flight, flight functions have become available to man via significant support from man-made structures and devices. Over the past 100 years or so, technology has enabled several flight functions to migrate to automation and/or decision support systems. This migration continues with the United States NextGen and Europe s Single European Sky (a.k.a. SESAR) initiatives. These overhauls of the airspace system will be accomplished by accommodating the functional capabilities, benefits, and limitations of technology and automation together with the unique and sometimes overlapping functional capabilities, benefits, and limitations of humans. This paper will discuss how a safe and effective migration of any flight function must consider several interrelated issues, including, for example, shared situation awareness, and automation addiction, or over-reliance on automation. A long-term philosophical perspective is presented that considers all of these issues by primarily asking the following questions: How does one find an acceptable level of risk tolerance when allocating functions to automation versus humans? How does one measure or predict with confidence what the risks will be? These two questions and others will be considered from the two most-discussed paradigms involving the use of increasingly complex systems in the future: humans as operators and humans as monitors.

Morris, Allan Terry↗
NASA NTRS2014

Test Driven Development of Scientific Models

Test-Driven Development (TDD), a software development process that promises many advantages for developer productivity and software reliability, has become widely accepted among professional software engineers. As the name suggests, TDD practitioners alternate between writing short automated tests and producing code that passes those tests. Although this overly simplified description will undoubtedly sound prohibitively burdensome to many uninitiated developers, the advent of powerful unit-testing frameworks greatly reduces the effort required to produce and routinely execute suites of tests. By testimony, many developers find TDD to be addicting after only a few days of exposure, and find it unthinkable to return to previous practices.After a brief overview of the TDD process and my experience in applying the methodology for development activities at Goddard, I will delve more deeply into some of the challenges that are posed by numerical and scientific software as well as tools and implementation approaches that should address those challenges.

Overview of TDD Process↗
NASA NTRS2020

Electromagnetic Pain Relief/Blocking: Feasibility Assessment

Context/Background: Astronauts use pharmaceuticals during spaceflight to manage acute and chronic pain, but use of analgesics will have drawbacks for exploration-class missions because the shelf life of these medications is limited, resupply will be curtailed, astronauts may develop tolerance and/or addiction to these medications, and side effects can include impairment of cognitive abilities. Electromagnetic devices have been developed that treat pain terrestrially by affecting neuromodulation–dubbed “electroceuticals”, these devices have varied mechanisms of action that either stimulate or suppress neural activity in the central nervous system or peripheral nerves. Objective/Purpose: The available literature was reviewed and FDA-approved pain treatments (both pharmacological and non-pharmacological), as well as those currently under development, were assessed for their suitability for use in exploration class spaceflight missions. Data Sources: Due to the COVID-19 pandemic and the resulting closure of libraries, data sources were restricted to those available digitally. Online database searches included PubMed, U.S. Patent and Trademark Office, federal grant award databases (National Aeronautics and Space Administration (NASA), Department of Defense (DoD), National Institutes of Health (NIH)), and general internet searches. More than 1,600 records were reviewed in this effort. Study Selection/Eligibility Criteria: Targeted searches included different aspects of pain management. Priority was given to review studies, to cover as much of the available literature as possible in this limited effort. Study Appraisal and Synthesis Methods/Data Extraction and Data Synthesis: The titles of the studies and the awards that were obtained by searching online databases were reviewed and further information was sought for the relevant titles. Abstracts or award summaries were generally available online; for journal abstracts, full text articles were either available online or were requested via interlibrary loan. Results: An overwhelming majority of the literature focuses on the treatment of chronic rather than acute pain because it is assumed that acute pain only rarely fails to resolve and instead transitions into chronic pain when the central nervous system becomes hypersensitized. The available electromagnetic devices marketed for pain treatment have varying levels of invasiveness, use different mechanisms of action, and have demonstrated varying efficacy when evaluated scientifically. A truly noninvasive, highly efficient device is desired for use during spaceflight. One portable, self-contained, FDA-approved device was identified that, from preliminarily assessment, best met these criteria; the device noninvasively applies pulsed shortwave therapy (PSWT) to modify pain signals from peripheral nerves, however, the device has limited battery life and the effects are relatively non-selective in type of neural signal modified. Limitations: This current effort, although extensive, did not identify a comprehensive list of all alternatives for pain treatment. Once the pandemic limitations are lifted, a longer, more thorough effort may find additional options. Conclusions/Implications: The ideal electromagnetic pain treatment device for use on exploration-class spaceflight missions does not yet exist, but it may be available soon. It is not feasible for NASA to develop medical devices due to the schedule constraints for pending exploration-class missions, but adapting a promising device that is already FDA-approved might be an option. Monitoring research that is ongoing at other federal agencies is recommended, and further review of the candidate PSWT device identified in this current effort may be warranted.

Carol Mullenax↗
NASA NTRS2020

Electromagnetic Pain Relief/Blocking

Astronauts use pharmaceuticals during spaceflight to manage acute and chronic pain, but use of analgesics will have drawbacks for exploration-class missions because the shelf life of these medications is limited, resupply will be curtailed, astronauts may develop tolerance and/or addiction to these medications, and side effects can include impairment of cognitive abilities. Electromagnetic devices have been developed that treat pain terrestrially by affecting neuromodulation – dubbed “electroceuticals”, these devices have varied mechanisms of action that either stimulate or suppress neural activity in the central nervous system or peripheral nerves. The available literature was reviewed and FDA-approved pain treatments (both pharmacological and non-pharmacological), as well as those currently under development, were assessed for their suitability for use in exploration-class spaceflight missions.

Carol A. Mullenax↗
NASA NTRSDate not supplied

Electromagnetic Pain Relief/Blocking: Feasibility Assessment

CONTEXT/BACKGROUND Astronauts use pharmaceuticals during spaceflight to manage acute and chronic pain, but use of analgesics will have drawbacks for exploration-class missions because the shelf life of these medications is limited, resupply will be curtailed, astronauts may develop tolerance and/or addiction to these medications, and side effects can include impairment of cognitive abilities. Electromagnetic devices have been developed that treat pain terrestrially by affecting neuromodulation–dubbed “electroceuticals”, these devices have varied mechanisms of action that either stimulate or suppress neural activity in the central nervous system or peripheral nerves. OBJECTIVE/PURPOSE The available literature was reviewed and FDA-approved pain treatments (both pharmacological and non-pharmacological), as well as those currently under development, were assessed for their suitability for use in exploration class spaceflight missions. DATA SOURCES Due to the COVID-19 pandemic and the resulting closure of libraries, data sources were restricted to those available digitally. Online database searches included PubMed, U.S. Patent and Trademark Office, federal grant award databases (National Aeronautics and Space Administration (NASA), Department of Defense (DoD), National Institutes of Health (NIH)), and general internet searches. More than 1,600 records were reviewed in this effort. STUDY SELECTION/ELIGIBILITY CRITERIA Targeted searches included different aspects of pain management. Priority was given to review studies, to cover as much of the available literature as possible in this limited effort. STUDY APPRAISAL AND SYNTHESIS METHODS/DATA EXTRACTION AND DATA SYNTHESIS The titles of the studies and the awards that were obtained by searching online databases were reviewed and further information was sought for the relevant titles. Abstracts or award summaries were generally available online; for journal abstracts, full text articles were either available online or were requested via interlibrary loan. RESULTS An overwhelming majority of the literature focuses on the treatment of chronic rather than acute pain because it is assumed that acute pain only rarely fails to resolve and instead transitions into chronic pain when the central nervous system becomes hypersensitized. The available electromagnetic devices marketed for pain treatment have varying levels of invasiveness, use different mechanisms of action, and have demonstrated varying efficacy when evaluated scientifically. A truly noninvasive, highly efficient device is desired for use during spaceflight. One portable, self-contained, FDA-approved device was identified that, from preliminarily assessment, best met these criteria; the device noninvasively applies pulsed shortwave therapy (PSWT) to modify pain signals from peripheral nerves, however, the device has limited battery life and the effects are relatively non-selective in type of neural signal modified. LIMITATIONS This current effort, although extensive, did not identify a comprehensive list of all alternatives for pain treatment. Once the pandemic limitations are lifted, a longer, more thorough effort may find additional options. CONCLUSIONS/IMPLICATIONS The ideal electromagnetic pain treatment device for use on exploration-class spaceflight missions does not yet exist, but it may be available soon. It is not feasible for NASA to develop medical devices due to the schedule constraints for pending exploration-class missions, but adapting a promising device that is already FDA-approved might be an option. Monitoring research that is ongoing at other federal agencies is recommended, and further review of the candidate PSWT device identified in this current effort may be warranted.

C A Mullenax↗
DOE OSTI2025

Cross‐Cultural Validation of the Binge Eating Disorder Screener‐7 ( BEDS ‐7) Across 42 Countries

ABSTRACT Objective This study aimed to evaluate the reliability and validity of the Binge Eating Disorder Screener‐7 (BEDS‐7) across 42 countries and 26 languages, assessing its reliability and validity as a screening tool for binge‐eating disorder (BED) in diverse cultural contexts. Specifically, it sought to enhance early recognition of BED symptoms in primary care settings globally, contributing to a standardized framework for assessing BED. Method The International Sex Survey, a cross‐sectional online study, was conducted in 42 countries and 26 languages. A diverse community sample of 82,243 participants, aged 18 years or older, completed the BEDS‐7 and measures of sexuality, mental health, substance use, and sociodemographic characteristics. Confirmatory factor analyses and tests of measurement invariance were employed to evaluate the reliability and validity of the BEDS‐7 across languages, countries, genders, and sexual orientations. Results The BEDS‐7 demonstrated scalar factorial invariance across languages and countries, indicating consistent factor loadings and item intercepts. In contrast, the screener showed residual invariance across gender and sexual orientation groups, supporting its robustness across these demographics. Kruskal–Wallis tests revealed significant differences in BED symptoms across languages, countries, genders, and sexual orientations, with the highest BED scores observed among queer, pansexual, and gender‐diverse individuals. The BEDS‐7 also demonstrated adequate reliability (Cronbach's alpha > 0.80) and moderate criterion validity. Discussion The findings provide further evidence of the reliability and validity of the BEDS‐7 as a potential screening tool for identifying probable cases of BED globally, facilitating early intervention in primary care settings.

Gewirtz‐Meydan, Ateret [School of Social Work, Fac↗
DOE OSTI2025

Contributions of major tau kinase activation and phospho-tau accumulation to cortical and hippocampal tangle formation and cognition in older adults

Aberrant activation of tau kinases (tauK) has been proposed as a major step in tau hyperphosphorylation and misfolding, and subsequent formation of neurofibrillary tangles (NFT) in Alzheimer's disease (AD). However, evidence of tauK hyperactivation in actual AD brains is scarce and inconsistent, and their role in age-related cognitive decline remains undocumented. We evaluated activated/inhibited species of CDK5/p35/p25, GSK3a/ß, and ERK1/2 as well as ten tau/phospho-tau (ptau) peptides (mapping Ser 202 , Thr 217 , Ser 262 , Ser 305 , and Ser 404 phospho-residues) by Western blot or selected reaction monitoring proteomics, respectively, in postmortem dorsolateral prefrontal cortex (DLPFC) and hippocampal samples of 150 participants from the Rush Memory and Aging Project (MAP). Regression models and mediation analyses assessed the contributions of these variables to tau phosphorylation, NFT deposition and antemortem cognitive status of MAP participants. Surprisingly, greater p25 and p35 (indices for CDK5 activation) and lower pSer 21/9 -GSK3a/ß (inhibited species) immunodensities were associated with lower ptau peptide amounts. Individuals with higher p25 cortical densities displayed better cognitive outcomes, particularly working memory. Statistical mediation analyses indicated that the beneficial effect of CDK5/p25 on cognition was mediated by lower densities of phospho-Thr 217 -tau and NFT deposition in DLPFC, and also identified Thr 217 and Ser 262 as the ptau sites with greatest influence in both NFT accumulation and cognitive impairment. The present data suggest that tau hyperphosphorylation, tangle deposition, and the subsequent cognitive impairment do not rely on aberrant activation of major tauKs. Additionally, novel evidence was provided for the beneficial contribution of cortical CDK5/p25 to the maintenance of working memory.

60 APPLIED LIFE SCIENCES↗