UK researchers awarded $2.6 million to study new drug combination driving overdose deaths

Grant and Award Announcement

UNIVERSITY OF KENTUCKY

 

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UK RESEARCHERS TERRY HINDS, JR. AND CASSANDRA GIPSON-REICHARDT WILL STUDY HOW XYLAZINE AND FENTANYL COMBINATION CHANGES THE BRAIN'S SIGNALING PATHWAYS.

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CREDIT: MARK CORNELISON | UNIVERSITY OF KENTUCKY PHOTO.

LEXINGTON, Ky. (Oct. 26, 2023) — Cassandra Gipson-Reichardt, Ph.D., and Terry Hinds, Jr., Ph.D., associate professors in the University of Kentucky College of Medicine’s Department of Pharmacology and Nutritional Sciences, have received a $2.65 million five-year grant from the National Institute on Drug Abuse (NIDA) to support research to understand how xylazine and fentanyl change the brain’s signaling pathways.  

Xylazine, a veterinary anesthetic commonly referred to as “tranq,” has recently made its way into the illicit drug supply as a drug adulterant to enhance the effects of fentanyl, a potent opioid that can be lethal even in small amounts. The new drug combination has resulted in a 1,127% increase in xylazine-positive overdose mortalities in the American south from 2020 to 2021, and results in other problematic health effects including tissue necrosis. 

This rapid spread of xylazine is also posing new challenges to addressing the opioid epidemic as it decreases the efficacy of naloxone, the life-saving medication that reverses the effects of an opioid overdose. 

Gipson-Reichardt and Hinds will study the specific brain circuits that are changed when xylazine and fentanyl are used together and see if these changes are responsible for making naloxone less effective. They have already identified unexpected pathways controlled by the combination that may reduce the actions of naloxone. In their work, they will determine if targeting these pathways are potentially therapeutic. 

Their team will utilize advanced PamGene PamStation technology in the Hinds lab to measure activities of hundreds of signaling mechanisms in the brain reward circuitry to identify how the co-use affects pathways and also to identify targets for therapeutic use.  

“By studying these processes in detail, we hope to better understand the ways xylazine and fentanyl interact in the brain and how they affect behavior,” said Gipson-Reichardt. “This knowledge could lead us to new strategies for treating people who are struggling with the combined use of these substances and help make naloxone more effective in saving lives.” 

These are the only preclinical studies currently funded by NIDA to address the xylazine/fentanyl epidemic, and will be the first to determine neurobiological and behavioral impacts of combined xylazine and fentanyl use and identify treatment targets to reverse xylazine’s effects on fentanyl. 

Gipson-Reichardt and Hinds will be collaborating with Kelly Dunn, Ph.D., at Johns Hopkins University to translate findings to inform the public on individual factors that may lead to worse clinical outcomes during withdrawal from the xylazine/fentanyl combination. 

Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R01DA058933. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 

As the state’s flagship, land-grant institution, the University of Kentucky exists to advance the Commonwealth. We do that by preparing the next generation of leaders — placing students at the heart of everything we do — and transforming the lives of Kentuckians through education, research and creative work, service and health care. We pride ourselves on being a catalyst for breakthroughs and a force for healing, a place where ingenuity unfolds. It's all made possible by our people — visionaries, disruptors and pioneers — who make up 200 academic programs, a $476.5 million research and development enterprise and a world-class medical center, all on one campus.   

In 2022, UK was ranked by Forbes as one of the “Best Employers for New Grads” and named a “Diversity Champion” by INSIGHT into Diversity, a testament to our commitment to advance Kentucky and create a community of belonging for everyone. While our mission looks different in many ways than it did in 1865, the vision of service to our Commonwealth and the world remains the same. We are the University for Kentucky.  

November issues of American Psychiatric Association journals cover new insights in psychotic disorders, barriers to addiction treatment, bipolar disorder treatment, and more

Peer-Reviewed Publication

AMERICAN PSYCHIATRIC ASSOCIATION

WASHINGTON, D.C., Nov. 1, 2023 — The latest issues of three American Psychiatric Association journals, The American Journal of Psychiatry, Psychiatric Services and Focus, are now available online.

The November issue of The American Journal of Psychiatry provides insights into psychotic disorders, such as the altered neurodevelopment and early symptom presentation associated with the risk of developing schizophrenia; racial and ethnic disparities in diagnosis of psychotic episodes; and predictors of first psychotic episodes and its treatment. Highlights include:

• A Functional Connectome-Based Neural Signature for Individualized Prediction of Antipsychotic Response in First-Episode Psychosis.      
• Are We There Yet? Predicting Conversion to Psychosis Using Machine Learning.
• Rethinking the First Episode of Schizophrenia: Identifying Convergent Mechanisms During Development and Moving Toward Prediction    
• Inequalities in the Incidence of Psychotic Disorders Among Racial and Ethnic Groups. (Lead investigator Winston Chung, M.D., is the featured guest on November’s AJP Audio podcast episode.)

The November issue of Psychiatric Services features:  
 

• Postmarket Surveillance for Effective Regulation of Digital Mental Health Treatments.
• Effect of a Layperson-Delivered Telephone Program for People with Depressive Symptoms.
• Uncovering Barriers to Engagement in Substance Use Disorder Care for Medicaid Enrollees.
• Unconditional Cash Transfers and Association with Clinical Outcomes Among U.S. Veterans with Psychosis or Recent Homelessness.
• Medicaid Costs and Utilization of Collaborative Versus Colocation Care for Patients with Depression. (Featured in the Psychiatric Services “From Pages to Practice” podcast.)

 

Also available online is the latest issue of Focus, Volume 21, Issue 4, a special issue on Bipolar Disorder. Helmed by Guest Editor Trisha Suppes, M.D., Ph.D., the issue features the following:
 

• The CANMAT and ISBD Guidelines for the Treatment of Bipolar Disorder: Summary and a 2023 Update of Evidence.
• Bipolar II Disorder: Understudied and Underdiagnosed.
• Cognition in Bipolar Disorder: An Update for Clinicians.
• Bipolar Disorder Among Older Adults: Newer Evidence to Guide Clinical Practice.
• Suicide Assessment and Prevention in Bipolar Disorder: How Current Evidence Can Inform Clinical Practice.
• Engaging Through the Elation: Forming an Early Therapeutic Rapport With a Patient With Bipolar Disorder.
   

Journalists who wish to access the publications should email press@psych.org.

American Psychiatric Association
The American Psychiatric Association, founded in 1844, is the oldest medical association in the country. The APA  is also the largest psychiatric association in the world with more than 38,000 physician members specializing in the diagnosis, treatment, prevention and research of mental illnesses. APA’s vision is to ensure access to quality psychiatric diagnosis and treatment. For more information, please visit www.psychiatry.org.

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JOURNAL

American Journal of Psychiatry

 

Giant dinosaur carcasses might have been important food sources for Jurassic predators

Simulation indicates traits for exploiting carrion could have been key to success

Peer-Reviewed Publication

PLOS

 

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PHOTOGRAPH OF THE SKELETAL MOUNT OF ALLOSAURUS SPECIMEN AMNH 5753, FROM WILLIAM DILLER MATTHEW'S 1915 DINOSAURS.

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CREDIT: PROJECT GUTENBERG E-BOOK, WIKIMEDIA COMMONS, CC0 (HTTPS://CREATIVECOMMONS.ORG/PUBLICDOMAIN/ZERO/1.0/)

Carnivorous dinosaurs might have evolved to take advantage of giant carcasses, according to a study published November 1, 2023 in the open-access journal PLOS ONE by Cameron Pahl and Luis Ruedas of Portland State University, Oregon and colleagues.

Carnivorous dinosaurs lived in ecosystems rich with both living and dead prey. The authors hypothesize that giant carcasses, like those of sauropod dinosaurs, might have provided a major source of food for large carnivores. To test this hypothesis, the researchers created an agent-based model, a simplified virtual simulation of a dinosaur ecosystem. This model was based on the ancient fauna of the Jurassic-aged Morrison Formation, which included large predators like Allosaurus alongside large sauropods, their carcasses, and an infinite supply of huntable stegosaurs.

In the model, carnivores (intended to simulate allosaurs) were assigned traits that would improve their hunting or scavenging abilities while obtaining energy from meat sources (simulating living prey or sauropod carcasses). The model measured the evolutionary fitness of these simulated carnivores and found that, when large sources of sauropod carrion were available, scavenging was more profitable than hunting, suggesting that carnivores in such ecosystems might have evolved specialized traits to help them detect and exploit large carcasses.

The authors stress that this model represents a simplified abstract of a complex system, and that the results might be altered with the inclusion of more variables, such as additional dinosaur species or features of the life history of the simulated dinosaurs. They note that models like this might improve our understanding of how the availability of carrion can influence the evolution of predators.

The authors add: “Our evolutionary model demonstrates that large theropods such as Allosaurus could have evolved to subsist on sauropod carrion as their primary resource. Even when huntable prey was available to them, selection pressure favored the scavengers, while the predators suffered from lower fitness. So we think allosaurs probably waited until a bunch of sauropods died in the dry season, feasted on their carcasses, stored the fat in their tails, then waited until the next season to repeat the process. This makes sense logically too, because a single sauropod carcass had enough calories to sustain 25 or so allosaurs for weeks or even months, and sauropods were often the most abundant dinosaurs in the environment.”

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In your coverage please use this URL to provide access to the freely available article in PLOS ONE: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0290459

Citation: Pahl CC, Ruedas LA (2023) Big boned: How fat storage and other adaptations influenced large theropod foraging ecology. PLoS ONE 18(11): e0290459. https://doi.org/10.1371/journal.pone.0290459

Author Countries: USA

Funding: The authors received no specific funding for this work.

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JOURNAL

PLoS ONE

DOI

10.1371/journal.pone.0290459 

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Big boned: How fat storage and other adaptations influenced large theropod foraging ecology

ARTICLE PUBLICATION DATE

1-Nov-2023

 

Game performance of immigrant NBA players might suffer in context of far-right political support

Researchers explore how far-right views might threaten workplace performance of top-skilled immigrants, such as NBA players

Peer-Reviewed Publication

PLOS

 

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GAME PERFORMANCE OF IMMIGRANT NBA PLAYERS MIGHT SUFFER IN CONTEXT OF FAR-RIGHT POLITICAL SUPPORT.

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CREDIT: QI XNA, UNSPLASH, CC0 (HTTPS://CREATIVECOMMONS.ORG/PUBLICDOMAIN/ZERO/1.0/)

During the 2020-2021 season of the National Basketball Association (NBA), which took place during Donald Trump’s failed bid at re-election, immigrant players for teams in regions with stronger far-right political sentiments were more likely to make game errors—highlighting the possible detrimental effects of such views on immigrant workplace performance. Benjamin Korman and Florian Kunze of the University of Konstanz, Germany, present these findings in the open-access journal PLOS ONE on November 1.

Prior research has shown that, in regions with strong support for far-right political parties, immigrants face more prejudice and discrimination. Evidence also suggests that being exposed to anti-immigrant propaganda may hinder immigrants’ performance on various tasks, and exposure to negative stereotypes about a certain group of people might boost the performance of people outside that group.

On the basis of such prior research and related psychological theory, Korman and colleagues propose that living in areas with far-right views might increase immigrants’ awareness of the possibility of being judged negatively as immigrants, disrupting their attention and causing them to make more workplace errors.

To investigate that hypothesis, they analyzed data on all 522 US-based NBA players’ game performance following the failed 2020 election bid of polarizing far-right politician Donald Trump.

The researchers found that immigrant players for teams based in regions with a higher percentage of presidential votes for Trump were more likely to make performance errors than immigrant players in regions with less Trump support. In contrast, the opposite was found for native players in the far-right regions. These results held true after statistically accounting for other factors that could impact performance, such as age, position, ball-possession time, number of possessions, salary and minutes of play time.

While this study does not confirm a cause-effect relationship, it provides some initial real-world support for the researchers’ hypothesis. On the basis of their findings, the researchers suggest that organizations might consider steps to insulate employees from regional far-right views by, for instance, banning employees from wearing politically charged clothing and fostering inclusive environments.

The researchers also note that their study addresses gaps in management research, which has typically ignored immigrant employees—especially those who are highly skilled—and the influence of the external political environment.

The authors add: “Using data on NBA players, this study highlights how the political environment external to organizations may seep into them, differentially affecting their immigrant and native members.”

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In your coverage please use this URL to provide access to the freely available article in PLOS ONE: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0289019

Citation: Korman BA, Kunze F (2023) Political context and immigrants’ work-related performance errors: Insights from the National Basketball Association. PLoS ONE 18(11): e0289019. https://doi.org/10.1371/journal.pone.0289019

Author Countries: Germany

Funding: The authors (BAK & FK) acknowledge funding from the Deutsche Forschungsgemeinschaft (DFG – German Research Foundation: [https://www.dfg.de] under Germany’s Excellence Strategy – EXC-2035/1 – 390681379. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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JOURNAL

PLoS ONE

DOI

10.1371/journal.pone.0289019 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Political context and immigrants’ work-related performance errors: Insights from the National Basketball Association

ARTICLE PUBLICATION DATE

1-Nov-2023

 

Wistar scientists engineer new NK cell engaging immunotherapy approaches to target and potentially treat recalcitrant ovarian cancer

Novel human Siglec-7 monoclonal and bispecific antibodies are being developed as potential future cancer immunotherapies

Peer-Reviewed Publication

THE WISTAR INSTITUTE

 

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THE WISTAR INSTITUTE'S DR. DAVID WEINER

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CREDIT: THE WISTAR INSTITUTE

PHILADELPHIA—(Nov. 1, 2023)—The Wistar Institute’s David B. Weiner, Ph.D., executive vice president, director of the Vaccine & Immunotherapy Center (VIC) and W.W. Smith Charitable Trust Distinguished Professor in Cancer Research, and collaborators, have engineered novel monoclonal antibodies that engage Natural Killer cells through a unique surface receptor that activates the immune system to fight against cancer. 

In their publication titled, “Siglec-7 glyco-immune binding MAbs or NK cell engager biologics induce potent anti-tumor immunity against ovarian cancers,” published in Science Advances, the team demonstrates the preclinical feasibility of utilizing these new cancer immunotherapeutic approaches against diverse ovarian cancer types, including treatment-resistant and refractory ovarian cancers — alone or in combination with checkpoint inhibitor treatment. 

The research started as a collaboration between Wistar’s Drs. Weiner and Mohamed Abdel-Mohsen, who were exploring the development of new glyco-signaling biologic tools that may be important in the fight against cancer.  

Ovarian cancer (OC) is frequently diagnosed late in the disease process, and OC resistance to currently available treatments make it especially problematic; according to the NIH, the chances of someone diagnosed with OC and surviving for five years is around fifty-fifty. Ovarian cancer demonstrates a low response rate to standard-of-care treatments like chemotherapies, PARP inhibitors and the widely used checkpoint inhibitor, PD-1. 

In the small proportion of ovarian cancer patients that do respond to these treatments, resistance becomes problematic over time — resulting in tumor escape and cancer progression. Genetic mutations, such as the well-known BRCA gene mutations, predispose women to a high risk of progressive OC. The CDC expects more than thirteen thousand women to die of ovarian cancer this year in the U.S. alone. 

To combat ovarian cancer treatment resistance, the team hypothesized that they might be able to engage not only the traditional T cell immune arm of the immune system which PD-1 and known checkpoint inhibitors (CPI) activate, but also implement a strategy to activate Natural killer cells (NK cells), a subset of important anti-tumor immune cells, through a conserved glyco-immune marker found on the surface of most NK cells called Siglec-7 (Sialic acid-binding immunoglobulin-type lectin). NK cells have been recently described to express Siglec-7, so the team tested two new strategies to engage and activate NK cells against ovarian cancer through Siglec-7. 

The first approach used human monoclonal antibodies (mAb) discovered and developed at Wistar and novel assays to visualize and demonstrate that certain anti-Siglec-7 mAbs could activate human NK cells — which, in the presence of the antibodies, responded against multiple human OC cell lines. These now-activated NK cells would kill OC but not non-cancer cells with the Siglec-7 mAb treatment. 

The researchers demonstrated that multiple OC carrying mutations, including BRCA1 and BRCA2, could be targeted by Siglec-7 antibodies through activated NK cells. The group moved to study the treatment of OC in a humanized mouse model and observed that the Siglec-7 treatment could impact OC growth slowing the tumors and increasing the animals’ survival.  

Having demonstrated the feasibility of utilizing a Siglec-7 mAb in OC models, the team thought there were additional ways to use the Siglec-7 mAb to further focus on OC disease. They hypothesized that directly fusing the Siglec-7 reactive binding site of the Siglec-7 mAb to a second mAb that uniquely binds late OC through a molecule named Follicle Stimulating Hormone receptor (FSHR), which they had previously developed, would create a targeted Siglec-7 bispecific antibody that could bind through two distinct targets creating a new class of NK cell engagers (NKCE). 

The team sought to test whether this Siglec-7 NKCE approach would be effective through the direct linkage of potentially killer NK cells to a guided missile aimed specifically at OC, which would open up a new path to develop additional Siglec-7 based immunotherapeutic approaches. In both bench and humanized mouse challenge studies, the Siglec-7-NKCE was effective at targeting OC, activating NK cells in local proximity and efficiently killing multiple OC. 

Both Siglec-7 technologies (mAbs and NKCEs) demonstrated an ability to recruit and activate the NK cell population, shrink tumors and prolong survival in the models studied. The observation of on-target specificity of the approaches suggests that cancer’s apparent Siglec vulnerability can be exploited therapeutically, perhaps with limited toxicity — a promising sign for the future of anti-cancer Siglec research, but the team cautions that more work in this regard is important. 

In an additional set of preliminary studies, the team also found that this Siglec-7 approach could complement PD-1 checkpoint inhibitor (CPI) therapy. This is an important area of further study that could uncover more details of the mechanisms involved and possibly extend the utility of such CPI in OC and, potentially, other cancers. “These findings open the door to further exploration of how we can engineer Siglec-7 immunotherapies and perhaps other related molecules for ovarian cancer and perhaps a larger group of recalcitrant cancers,” stated Dr. David B. Weiner, adding, “Further studies may bring such approaches as described to represent new tools in our antitumor toolbelt.” 

As always, more research is needed to refine these technologies further on the long journey from the lab bench to the clinic. But this paper offers a different avenue for attempting to exploit these unique interactions of immune surface molecules such as Siglec-7 and perhaps other Siglecs.   

“We have observed not one but two methods that can target NK cells in an effort to control ovarian cancer in both Petri dishes and in vivo models,” said Dr. Devivasha Bordoloi, the first author on the paper. “This research shows a lot of promise, and I’m excited to move these studies to the next steps.” 

Co-authors: Devivasha Bordoloi, Abhijeet J. Kulkarni, Opeyemi S. Adeniji, Pratik S. Bhojnagarwala, Shushu Zhao, Candice Ionescu, Alfredo Perales-Puchalt, Elizabeth M Parzych, Xizhou Zhu, Ali R. Ali, Joel Cassel, Rugang Zhang, Mohamed Abdel-Mohsen and David B. Weiner of The Wistar Institute; and M. Betina Pampena and Michael R. Betts of Perelman School of Medicine, University of Pennsylvania,

Work supported by: Department of Defense Ovarian Cancer Research Program award W81XWH-19-1-0189; the W.W. Smith Charitable Trust Professorship in Cancer Research; and the Wistar Science Accelerator Postdoctoral Fellowship.

Publication information: “Siglec-7 glyco-immune binding MAbs or NK cell engager biologics induce potent anti-tumor immunity against ovarian cancers,” from Science Advances

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The Wistar Institute, the first independent, nonprofit biomedical research institute in the United States, marshals the talents of an international team of outstanding scientists through a culture of biomedical collaboration and innovation. Wistar scientists are focused on solving some of the world’s most challenging and important problems in the field of cancer, infectious disease, and immunology. Wistar has been producing groundbreaking advances in world health for more than a century, consistent with its legacy of leadership in biomedical research and a track record of life-saving contributions in immunology and cell biology. wistar.org.
 

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JOURNAL

Science Advances

DOI

10.1126/sciadv.adh4379 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Siglec-7 glyco-immune binding MAbs or NK cell engager biologics induce potent anti-tumor immunity against ovarian cancers

 

“Peace speech” in the media characterizes a country’s peaceful culture

Per analysis of linguistic patterns, English media in high-peace countries feature words reflecting hope and fun; in low-peace countries, there are more references to control and fear

Peer-Reviewed Publication

PLOS

 

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WORDS IN NEWS MEDIA MORE ASSOCIATED WITH MORE PEACEFUL COUNTRIES.

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CREDIT: LARRY S. LIEBOVITCH, CC-BY 4.0 (HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY/4.0/)

By analyzing the frequency of certain words within mainstream news media from any country, a machine learning algorithm can produce a quantitative “peace index” that captures the level of peace within that country, according to a new study published this week in the open-access journal PLOS ONE by Larry Liebovitch and Peter T. Coleman of Columbia University, US, and colleagues.

The language used in media both reflects a culture’s view of the world and influences how people within the culture think and act. “Hate speech” can mobilize violence and destruction. Much less is known about how “peace speech” characterizes peaceful cultures and may help to generate or sustain peace.

In the new study, Liebovitch and colleagues used five previously developed and highly respected peace indices to capture levels of peace within 18 countries classified as high-peace, intermediate-peace or low-peace. They then collected 723,574 media articles originating from these countries; all were written by local sources and published online in English.

Using only the high-peace and low-peace countries, the researchers used a machine learning model to identify words whose use in the media was associated with levels of peace. Overall, lower-peace countries were characterized by the higher prevalence of words related to government, order, control and fear (such as government, state, law, security and court), while higher-peace countries were characterized by an increased prevalence of words related to optimism for the future and fun (such as time, like, home, believe and game). When the researchers applied the trained machine learning model to media from the intermediate-peace countries that had not originally been included, the model correctly identified the countries as having intermediate levels of peace.

The authors point out that their data was biased in that all the sources were in English, which means the authors' model is more reliable in evaluating countries where English is a more common language for news communication. Additionally, the method may include bias already integrated into the preconceived peace indices used in the work.

Despite the limitations, the authors conclude that the data serves as a good starting point to further explore the linguistic differences between lower-peace and high-peace cultures.  

The authors add: “We used machine learning to find the words in local news media that best indicate the level of peace in a country. In less peaceful countries, news media focus on government and social control, while in more peaceful countries, its focus is on personal preferences and the activities of everyday life. We also found that high-peace countries evidenced a much higher level of diversity of terms than low-peace countries.”

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In your coverage please use this URL to provide access to the freely available article in PLOS ONE: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0292604

Citation: Liebovitch LS, Powers W, Shi L, Chen-Carrel A, Loustaunau P, Coleman PT (2023) Word differences in news media of lower and higher peace countries revealed by natural language processing and machine learning. PLoS ONE 18(11): e0292604. https://doi.org/10.1371/journal.pone.0292604

Author Countries: USA

Funding: The authors received no specific funding for this work.

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JOURNAL

PLoS ONE

DOI

10.1371/journal.pone.0292604 

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Word differences in news media of lower and higher peace countries revealed by natural language processing and machine learning

ARTICLE PUBLICATION DATE

1-Nov-2023

 

Gulf War Illness significantly reduces white blood cells’ ability to make energy

VA physician noticed symptoms parallel to mitochondrial diseases

Peer-Reviewed Publication

DUKE UNIVERSITY

 

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US TROOPS IN THE PERSIAN GULF WAR (1991). GULF WAR ILLNESS (GWI), WHICH AFFECTS APPROXIMATELY 250,000 U.S. VETERANS, HAS BEEN FOUND TO SIGNIFICANTLY REDUCE THE ABILITY OF WHITE BLOOD CELLS TO MAKE ENERGY AND CREATES A MEASURABLE BIOCHEMICAL DIFFERENCE IN VETERANS WHO HAVE THE DISEASE.

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CREDIT: US DEPARTMENT OF DEFENSE

DURHAM, N.C.— A new Duke University-led study finds that Gulf War Illness (GWI), which affects approximately 250,000 U.S. veterans, significantly reduces their white blood cells’ ability to make energy and creates a measurable biochemical difference in veterans who have the disease.

“Historically, GWI has been diagnosed based on a veteran’s self-reported symptoms, such as exercise-induced fatigue, indigestion, dizziness, insomnia, or memory problems. There’s been no objective biochemical or molecular measurements doctors could use to diagnose it,” said Joel Meyer, professor of environmental genomics at Duke’s Nicholas School of the Environment, who led the new study.

The new study provides measurements accessible in blood samples, which, though not sufficient to serve as a stand-alone diagnostic test, could be useful to help improve treatment for veterans suffering from Gulf War Illness by giving doctors a new way to assess whether a prescribed treatment is helping, Meyer said.

“Knowing this is an energetic deficiency can help us zero in on more effective ways to relieve the symptoms,” Meyer said. “Blood tests, repeated over the course of the treatment, would show if a veteran’s white blood cells are responding to a treatment and producing more energy.”

He and his coauthors from Duke, the U.S. Department of Veteran Affairs’ War-Related Illness and Injury Study Center, and the New Jersey Medical School published the new peer-reviewed paper Nov. 1 in the open-access journal PLOS ONE.

Their research reveals that Gulf War Illness inhibits white blood cells’ energy production by impairing the workings of the cells’ mitochondria, structures within the cell which extract energy from food and convert it into the chemical power needed to fuel growth, movement and other bodily processes and functions. Mitochondria are often referred to as the ‘power plants’ of the cell.

“The idea to investigate the role mitochondria might be playing in GWI came from Mike Falvo, one of my coauthors from Veteran Affairs and the New Jersey Medical School, who had noticed that a lot of GWI symptoms were similar to those associated with mitochondrial diseases,” said Meyer. “So, we analyzed mitochondrial respiration and extracellular acidification, which are proxies for energy generation, in the white blood cells of 114 Gulf War veterans, 80 of whom had been diagnosed with GWI. We also looked for evidence of mitochondrial DNA damage and nuclear DNA damage.”

The analyses revealed no evidence of DNA damage, but they did show significantly lower levels of extracellular acidification and oxygen consumption in the white blood cells from veterans with GWI—signs that their mitochondria were generating less energy.  

Follow-up blood tests on about a third of the veterans showed that some of these levels could vary over time, but the general pattern remained: the cells of veterans with GWI produced less energy.

The cause of Gulf War Illness is still unknown. To determine if environmental factors might play a role, Meyer and his colleagues turned to the veterans’ surveys of self-reported symptoms and their written recollections of their deployments.

“We found veterans who recalled being exposed to pesticides and pyridostigmine bromide, a drug used during the Gulf War as a pretreatment to protect troops from the harmful effects of nerve agents, were more likely to get GWI after deployment,” Meyer said. “An interesting question is how these effects have persisted so long after the exposures.”   

Coauthors on the new paper were William Pan and Ian Ryde of Duke; Thomas Alexander, Jacquelyn Klein-Adams and Duncan Ndirangu of the U.S. Department of Veteran Affairs’ War-Related Illness and Injury Study Center (WRIISC); and Michael Falvo of WRIISC and the New Jersey Medical School at Rutgers Biomedical and Health Science.

Funding came from the Office of the Assistant Secretary of Defense for Health Affairs through the Gulf War Illness Research Program (W81XWH-16-1-0663), with additional support from the U.S. Department of Veterans Affairs Clinical Sciences Research and Development Service (#I01 CX001329). The conclusions, opinions, interpretations and recommendations contained in the paper are those of its authors and are not necessarily endorsed by the Department of Defense or Department of Veteran Affairs.

CITATION: “Bioenergetic Function is Decreased in Peripheral Blood Mononuclear Cells of Veterans with Gulf War Illness,” Joel N. Meyer, William K. Pan, Ian T. Ryde, Thomas Alexander, Jacquelyn C. Klein-Adams, Duncan S. Ndirangu and Michael J. Falvo. PLOS ONE, Nov. 1, 2023, 2023. DOI: 10.1371/journal.pone.0287412

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JOURNAL

PLoS ONE

DOI

10.1371/journal.pone.0287412 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Bioenergetic Function is Decreased in Peripheral Blood Mononuclear Cells of Veterans with Gulf War Illness

ARTICLE PUBLICATION DATE

1-Nov-2023