The rhythm led by plants is crucial for symbiosis with nutrient-providing bacteria

Discovery that symbiosis with rhizobia in legumes is regulated by oscillating gene expression

NATIONAL INSTITUTES OF NATURAL SCIENCES

 

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SYMBIOSIS WITH RHIZOBIA IN LEGUMES IS REGULATED BY OSCILLATING GENE EXPRESSION

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CREDIT: NIBB

Legumes thrive in low-nitrogen environments by partnering with rhizobia, soil bacteria that convert atmospheric nitrogen into ammonium, a usable form for the plants. These beneficial bacteria are housed in root nodules formed on legume roots. However, the uncontrolled formation of numerous root nodules can impede root function. To prevent this, legumes need to regulate the distribution and number of root nodules, but the precise mechanisms were previously unclear.

Recent research on Lotus japonicus, a model leguminous plant, has unveiled that the interaction between legume roots and rhizobia is characterized by periodic gene expression with a six-hour rhythm. This rhythmic gene expression influences the regions of the root susceptible to rhizobial infection and the distribution of nodules. It was also discovered that the plant hormone cytokinin is crucial for maintaining this gene expression rhythm. This groundbreaking study, published in Science, is a collaborative effort conducted by the National Institute for Basic Biology, Nara Institute of Science and Technology, Hokkaido University, Kwansei Gakuin University, RIKEN, and Aichi University of Education.

When rhizobia infect legume roots, root epidermal cells form infection threads, membranous tube-like structures guiding the bacteria to the inner root tissue where they can fix nitrogen. Rhizobial infection primarily occurs in a narrow root region just behind the root tip, known as the susceptible region. The continuous cell generation at the root tip perpetually creates new susceptible regions. Ideally, infection threads would be evenly distributed throughout the root. However, closer examination reveals a pattern of densely formed infection threads alternating with sparser regions, suggesting intermittent rather than continuous responses to rhizobia. Detailed studies on the dynamic response of roots to rhizobia over time have been lacking.

Using luminescence live-imaging with luciferase as a reporter, the research team observed that NSP1 gene expression, rapidly induced in response to rhizobia and essential for the infection process, exhibited oscillatory patterns at approximately six-hour intervals in the susceptible region. As the root grew, new expression sites appeared apically to the previous oscillation regions. "We noticed that these oscillation regions coincide with areas where infection threads are densely formed, leading us to think that this rhythmic gene expression might be related to the determination of nodule formation sites," said Dr. Takashi Soyano, Associate Professor of the National Institute for Basic Biology, a member of the research team. Consistent with this notion, a large population of root nodules was formed in the oscillation region, suggesting a link between rhythmic gene expression and nodule formation. Other genes essential for early responses during nodule symbiosis also displayed oscillatory expression patterns, marking the first evidence of periodic gene expression in response to rhizobia.

Cytokinin, a key regulator in root nodule symbiosis, maintains this oscillatory gene expression. Genes related to cytokinin biosynthesis, metabolism, and signaling exhibited oscillatory expression after rhizobial inoculation. Luminescence imaging using the cytokinin response marker TCSn revealed oscillatory cytokinin responses, aligning with the timing of active cytokinin content fluctuations.

The study utilized mutants of a cytokinin receptor LHK1 to explore cytokinin's role in gene expression periodicity. In mutants lacking functional LHK1, oscillating intervals of the periodic NSP1 expression were prolonged, expanding the root region where NSP1 expression oscillates. Conversely, in plants transformed with an activated form of LHK1, the induction of NSP1 expression was suppressed, leading to loss of its periodicity. The NSP1 oscillation region coincided with the area forming dense infection threads. The lhk1 loss-of-function mutants exhibited enlarged root segments forming dense infection threads, whereas the active LHK1 reduced infection thread densities. These findings underscore the importance of proper cytokinin response in maintaining the symbiotic oscillation and ensuring appropriate infection thread distribution.

Root nodule symbiosis occurs in the monophyletic nitrogen-fixing clade, including four orders, Fabales, Rosales, Cucurbitales, and Fagales, indicating a shared evolutionary acquisition to interact with nitrogen-fixing bacteria. Among them, the legume family in the order Fabales, where most of the species engaged in root nodule symbiosis, uniquely incorporated the cytokinin pathway as an important regulatory module for the symbiosis. "The discovery of periodic cytokinin responses was unexpected, raising several questions, including the molecular mechanisms that establish this periodicity and how these periodic responses shape the infection regions, " Dr. Soyano said. Addressing these questions is expected to deepen the understanding of the regulatory mechanisms of root nodule symbiosis and advance research on the spatial control of organ development through periodic responses mediated by plant hormones.

Spatio-temporal expression pat [VIDEO] 

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JOURNAL

Science

DOI

10.1126/science.adk5589 

METHOD OF RESEARCH

Experimental study

ARTICLE TITLE

Periodic cytokinin responses in Lotus japonicus rhizobium infection and nodule development

ARTICLE PUBLICATION DATE

19-Jul-2024

New humidity-driven membrane to remove carbon dioxide from the air

A new ambient-energy-driven membrane that pumps carbon dioxide out of the air has been developed by Newcastle University researchers.

NEWCASTLE UNIVERSITY

Direct air capture was identified as one of the ‘Seven chemical separations to change the world’. This is because although carbon dioxide is the main contributor to climate change (we release ~40 billion tons into the atmosphere every year), separating carbon dioxide from air is very challenging due to its dilute concentration (~0.04%).

Prof Ian Metcalfe, Royal Academy of Engineering Chair in Emerging Technologies in the School of Engineering, Newcastle University, UK, and lead investigator states, “Dilute separation processes are the most challenging separations to perform for two key reasons. First, due to the low concentration, the kinetics (speed) of chemical reactions targeting the removal of the dilute component are very slow. Second, concentrating the dilute component requires a lot of energy.”

These are the two challenges that the Newcastle researchers (with colleagues at the Victoria University of Wellington, New Zealand, Imperial College London, UK, Oxford University, UK, Strathclyde University, UK and UCL, UK) set out to address with their new membrane process. By using naturally occurring humidity differences as a driving force for pumping carbon dioxide out of air, the team overcame the energy challenge. The presence of water also accelerated the transport of carbon dioxide through the membrane, tackling the kinetic challenge.

The work is published in Nature Energy and Dr Greg A. Mutch, Royal Academy of Engineering Fellow in the School of Engineering, Newcastle University, UK explains, “Direct air capture will be a key component of the energy system of the future. It will be needed to capture the emissions from mobile, distributed sources of carbon dioxide that cannot easily be decarbonised in other ways.”

“In our work, we demonstrate the first synthetic membrane capable of capturing carbon dioxide from air and increasing its concentration without a traditional energy input like heat or pressure. I think a helpful analogy might be a water wheel on a flour mill. Whereas a mill uses the downhill transport of water to drive milling, we use it to pump carbon dioxide out of the air.”

Separation processes

Separation processes underpin most aspects of modern life. From the food we eat, to the medicines we take, and the fuels or batteries in our car, most products we use have been through several separation processes. Moreover, separation processes are important for minimising waste and the need for environmental remediation, such as direct air capture of carbon dioxide.

However, in a world moving towards a circular economy, separation processes will become even more critical. Here, direct air capture might be used to provide carbon dioxide as a feedstock for making many of the hydrocarbon products we use today, but in a carbon-neutral, or even carbon-negative, cycle.

Most importantly, alongside transitioning to renewable energy and traditional carbon capture from point sources like power plants, direct air capture is necessary for realising climate targets, such as the 1.5 °C goal set by the Paris Agreement.

The humidity-driven membrane

Dr Evangelos Papaioannou, Senior Lecturer in the School of Engineering, Newcastle University, UK explains, “In a departure from typical membrane operation, and as described in the research paper, the team tested a new carbon dioxide-permeable membrane with a variety of humidity differences applied across it. When the humidity was higher on the output side of the membrane, the membrane spontaneously pumped carbon dioxide into that output stream.”

Using X-ray micro-computed tomography with collaborators at UCL and the University of Oxford, the team were able to precisely characterise the structure of the membrane. This enabled them to provide robust performance comparisons with other state-of-the-art membranes.

A key aspect of the work was modelling the processes occurring in the membrane at the molecular scale. Using density-functional-theory calculations with a collaborator affiliated to both Victoria University of Wellington and Imperial College London, the team identified ‘carriers’ within the membrane. The carrier uniquely transports both carbon dioxide and water but nothing else. Water is required to release carbon dioxide from the membrane, and carbon dioxide is required to release water. Because of this, the energy from a humidity difference can be used to drive carbon dioxide through the membrane from a low concentration to a higher concentration.

Prof Metcalfe adds, “This was a real team effort over several years. We are very grateful for the contributions from our collaborators, and for the support from the Royal Academy of Engineering and the Engineering & Physical Sciences Research Council.”

Reference: Separation and concentration of carbon dioxide from air using a humidity-driven molten-carbonate membrane. I.S. Metcalfe, G.A. Mutch, E.I. Papaioannou, S. Tsochataridou, D. Neagu, D.J.L. Brett, F. Iacoviello, T.S. Miller, P.R. Shearing, P.A. Hunt. Nature Energy. DOI: 10.1038/s41560-024-01588-6

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JOURNAL

Nature Energy

DOI

10.1038/s41560-024-01588-6 

METHOD OF RESEARCH

Computational simulation/modeling

ARTICLE TITLE

Separation and concentration of CO2 from air using a humidity-driven molten-carbonate membrane

ARTICLE PUBLICATION DATE

19-Jul-2024

U$A

How well does Medicare cover end-of-life care? It depends on what type

A new study analyzed the experiences of more than a million patients in their final months of life.

Peer-Reviewed Publication

UNIVERSITY OF COLORADO ANSCHUTZ MEDICAL CAMPUS

Not all versions of Medicare are created equal – and when it comes to end-of-life care, some versions may serve a patient’s needs better than others. That’s the focus of newly published research by Lauren Hersch Nicholas, PhD, MPP, a University of Colorado Department of Medicine and CU Cancer Center health economist, and her colleagues.

The researchers analyzed the experiences of more than a million people receiving Medicare-funded services in the last six months of their lives. Many of these patients had one or more life-limiting illnesses at the time of death, including cancer, dementia, and end-stage organ failure.

Their paper was published July 19 in JAMA Health Forum.

What Nicholas and her colleagues found is that the kind of Medicare a patient is enrolled in can make a difference in whether that patient gets certain treatments, and whether the patient dies in a hospital or in hospice care.

No one right answer

Nicholas and her colleagues examined two broad types of Medicare: Traditional Medicare, the hospital and medical insurance programs (Parts A and B) provided by the government; and Medicare Advantage Plans, the alternative coverage provided by Medicare-approved private companies.

“Medicare Advantage is a managed care option that includes additional benefits along with limited provider networks,” Nicholas says. “Traditional Medicare offers more flexibility in which doctors patients can see but less financial protection.”

→ ‘Primary Care Is a Different Animal’: Bennett Parnes, MD, Says Paying Attention is Key to Helping Older Patients

As to which version of Medicare is best for end-of-life patients, the results suggest there is no one right answer for everyone because the needs and wishes of patients and their families differ.

“None of us want to think about getting sicker,” says Nicholas, a professor in the Division of Geriatric Medicine who’s also on the faculty of the CU Center for Bioethics and Humanities. “But the Medicare plan that you choose when you’re relatively healthy may have implications for what care you’re able to access down the line.”

‘Potentially burdensome’

Nicholas says her new study “united two of my long-term research interests. I’ve been working on differences in Medicare since my dissertation research, which was focused mostly on quality of care and potentially preventable hospitalizations. And I’ve also done a lot of work on end-of-life care, where we have a lot of quality challenges, and where we spend a ton of money on care that patients and their families later are often not happy about, so it’s an area with great potential for improvement.”

The researchers analyzed claims records covering the last six months of life of 360,430 people nationwide enrolled in Medicare Advantage and 659,135 traditional Medicare enrollees who died between 2016 and 2018. About half of those in both groups had various life-limiting illnesses.

→ ‘Putting All the Pieces Together’: Data Drives Work to Improve Home Health Care

For some of these patients, certain invasive treatments – including mechanical ventilation, feeding or breathing tubes, intravenous feeding, or dialysis – could be what the study terms “potentially burdensome,” meaning they “are costly and do not significantly extend length of life or improve quality of life.” For other patients, such treatments might be classified as “appropriate.”

Likewise, the study says, frequent hospitalizations in the last few months of life may be of less benefit to some patients than others. “Despite preferences for home, patients often die in hospitals and nursing homes, experiencing transitions from one health care setting of care to another late in life,” the study says.

Concerning patterns

The study notes that Medicare Advantage is a managed-care alternative to traditional Medicare’s fee-for-service model. Companies that provide Medicare Advantage plans get fixed monthly payments per enrollee regardless of actual service use. As such, Medicare Advantage is designed to reduce over-utilization of medical services.

“For patients near the end-of-life, [Medicare Advantage] incentives may reduce potentially burdensome care and encourage hospice,” Nicholas’ paper says, “but could also restrict access to costly but necessary services.”

→ Older Adults Train to Recruit Their Peers, and Other Underrepresented Groups, into Clinical Trials

Nicholas says her research found that “Medicare Advantage was associated with generally less aggressive health care utilization near the end of life – fewer hospitalizations and less invasive medical care if you are hospitalized, lower rates of things like feeding tubes and dialysis and mechanical ventilations.

“But there were also some concerning patterns,” she adds. “Once a patient was hospitalized, those in Medicare Advantage were more likely to die in the hospital than elsewhere, which could mean that the hospitalization came after care was delayed and nothing else could be done.”

Nicholas says that Medicare Advantage “does have a number of features and incentives that could improve the quality of care for some end-of-life patients, but you might also worry about these plans denying some treatments and leaving very sick, vulnerable people with unmet needs.”

Hospitalization and hospice

Among the study’s key findings:

• Medicare Advantage patients in the study were less likely to receive potentially burdensome treatments in the last six months of life than patients enrolled in traditional Medicare.
• If hospitalized in the last six months of life, the Medicare Advantage patients were more likely to die in the hospital than were traditional-Medicare enrollees, who were more likely to die elsewhere, including in hospice care.
• If hospitalized in the last six months of life and then discharged, Medicare Advantage patients were less likely to receive care at skilled nursing facilities than traditional-Medicare patients, and more likely to receive their end-of-life care at home.
• “Receipt of less facility-based and potentially burdensome care near the end-of-life may improve quality of care” for Medicare Advantage patients, the study concludes. “However, the greater reliance on home-based care may leave patients with unmet needs or relying on informal care assistance” from family members or others.  

Having a conversation

“Our research points to the need to have a family conversation about the end of life, and what family members do or don’t want to do to help with that,” Nicholas says.

Nicholas notes that her study did not distinguish between traditional-Medicare patients who also had a supplemental private insurance plan (often known as Medigap) to pay extra costs, and those without a Medigap plan. The study also did not differentiate among the various Medicare Advantage Plans, which often charge different out-of-pocket costs and have different rules for service.

Co-authors of the study include CU Department of Medicine faculty members Stacy Fischer, MD, and Christine Jones, MD, as well as Marcelo Perraillon, PhD, of the Colorado School of Public Health. Fischer and Perraillon are also CU Cancer Center members. Alicia Arbaje, MD, PhD, and Daniel Polsky, PhD, both at Johns Hopkins University, also co-authored.

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JOURNAL

JAMA Health Forum

DOI

10.1001/jamahealthforum.2024.1777 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Medicare-Covered Services Near the End of Life in Medicare Advantage vs Traditional Medicare

ARTICLE PUBLICATION DATE

19-Jul-2024

COI STATEMENT

Dr Nicholas reported grants from the National Institute on Aging (NIA) during the conduct of the study; grants from the Leukemia & Lymphoma Society and grants NIA outside the submitted work. Dr Fischer reported grants from NIA (7R56AG065369-02) during the conduct of the study; grants from the National Institutes of Health (NIH) and grants from the American Cancer Society outside the submitted work. Dr Arbaje reported grants from NIA during the conduct of the study; grants from the Agency for Healthcare Research and Quality outside the submitted work. Dr Perraillon reported grants from the National Cancer Institute (NCI; R01CA22599) during the conduct of the study. Dr Jones reported grants from Veterans Affairs Office of Research and Development, grants from NIH, and grants from Commonwealth Foundation outside the submitted work. Dr Polsky reported grants from NIH during the conduct of the study; grants from Arnold Ventures, grants from NIH, and personal fees from Amazon outside the submitted work.

 

Study shows promise for a universal influenza vaccine

OHSU-led research uses innovative vaccine platform to target interior of virus; scientists validate theory using 1918 flu virus

OREGON HEALTH & SCIENCE UNIVERSITY

 

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JONAH SACHA, PH.D., SENIOR CO-AUTHOR OF A STUDY PUBLISHED TODAY IN THE JOURNAL NATURE COMMUNICATIONS, SAYS THE RESEARCH COULD LEAD TO A UNIVERSAL INFLUENZA VACCINE WITHIN FIVE YEARS.

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CREDIT: OHSU/CHRISTINE TORRES HICKS

New research led by Oregon Health & Science University reveals a promising approach to developing a universal influenza vaccine — a so-called “one and done” vaccine that confers lifetime immunity against an evolving virus.

The study, published today in the journal Nature Communications, tested an OHSU-developed vaccine platform against the virus considered most likely to trigger the next pandemic.

Researchers reported the vaccine generated a robust immune response in nonhuman primates that were exposed to the avian H5N1 influenza virus. But the vaccine wasn’t based on the contemporary H5N1 virus; instead, the primates were inoculated against the influenza virus of 1918 that killed millions of people worldwide.

“It’s exciting because in most cases, this kind of basic science research advances the science very gradually; in 20 years, it might become something,” said senior author Jonah Sacha, Ph.D., professor and chief of the Division of Pathobiology at OHSU’s Oregon National Primate Research Center. “This could actually become a vaccine in five years or less.”

Researchers reported that six of 11 nonhuman primates inoculated against the virus that circulated a century ago — the 1918 flu — survived exposure to one of the deadliest viruses in the world today, H5N1. In contrast, a control group of six unvaccinated primates exposed to the H5N1 virus succumbed to the disease.

Sacha said he believes the platform “absolutely” could be useful against other mutating viruses, including SARS-CoV-2.

“It’s a very viable approach,” he said. “For viruses of pandemic potential, it’s critical to have something like this. We set out to test influenza, but we don’t know what’s going to come next.”

A senior co-author from the University of Pittsburgh concurred.

“Should a deadly virus such as H5N1 infect a human and ignite a pandemic, we need to quickly validate and deploy a new vaccine,” said co-corresponding author Douglas Reed, Ph.D., associate professor of immunology at the University of Pittsburgh Center for Vaccine Research.

Finding a stationary target

This approach harnesses a vaccine platform previously developed by scientists at OHSU to fight HIV and tuberculosis, and in fact is already being used in a clinical trial against HIV.

The method involves inserting small pieces of target pathogens into the common herpes virus cytomegalovirus, or CMV, which infects most people in their lifetimes and typically produces mild or no symptoms. The virus acts as a vector specifically designed to induce an immune response from the body’s own T cells.

This approach differs from common vaccines — including the existing flu vaccines — which are designed to induce an antibody response that targets the most recent evolution of the virus, distinguished by the arrangement of proteins covering the exterior surface.

“The problem with influenza is that it’s not just one virus,” Sacha said. “Like the SARS-CoV-2 virus, it’s always evolving the next variant and we’re always left to chase where the virus was, not where it’s going to be.”

The spike proteins on the virus exterior surface evolve to elude antibodies. In the case of flu, vaccines are updated regularly using a best estimate of the next evolution of the virus. Sometimes it’s accurate, sometimes less so.

In contrast, a specific type of T cell in the lungs, known as effector memory T cell, targets the internal structural proteins of the virus, rather than its continually mutating outer envelope. This internal structure doesn’t change much over time — presenting a stationary target for T cells to search out and destroy any cells infected by an old or newly evolved influenza virus.

Success with a century-old template

To test their T cell theory, researchers designed a CMV-based vaccine using the 1918 influenza virus as a template. Working within a highly secure biosafety level 3 laboratory at the University of Pittsburgh, they exposed the vaccinated nonhuman primates to small particle aerosols containing the avian H5N1 influenza virus — an especially severe virus that is currently circulating among dairy cows in the United States.

Remarkably, six of the 11 vaccinated primates survived the exposure, despite the century-long period of virus evolution.

“It worked because the interior protein of the virus was so well preserved,” Sacha said. “So much so, that even after almost 100 years of evolution, the virus can’t change those critically important parts of itself.”

The study raises the potential for developing a protective vaccine against H5N1 in people.

“Inhalation of aerosolized H5N1 influenza virus causes a cascade of events that can trigger respiratory failure,” said co-senior author Simon Barratt-Boyes, Ph.D., professor of infectious diseases, microbiology and immunology at Pitt. “The immunity induced by the vaccine was sufficient to limit virus infection and lung damage, protecting the monkeys from this very serious infection.”

By synthesizing more up-to-date virus templates, the new study suggests CMV vaccines may be able to generate an effective, long-lasting immune response against a wide suite of new variants.

“I think it means within five to 10 years, a one-and-done shot for influenza is realistic,” Sacha said.

The same CMV platform developed by OHSU researchers has advanced to a clinical trial to protect against HIV, and a recent publication by those scientists suggests it may even be useful targeting specific cancer cells. The HIV clinical trial is being led by Vir Biotechnology, which licensed the vaccine platform from OHSU.

Sacha sees the development as the latest in the rapid advance of medical research to treat or prevent disease.

“It’s a massive sea change within our lifetimes,” Sacha said. “There is no question we are on the cusp of the next generation of how we address infectious disease.”

In addition to OHSU, research institutions involved in the study included the Tulane National Primate Research Center, the University of Pittsburgh, the University of Washington, and the Washington National Primate Research Center at the UW.

In the interest of ensuring the integrity of our research and as part of our commitment to public transparency, OHSU actively regulates, tracks and manages relationships that our researchers may hold with entities outside of OHSU. In regard to this research, OHSU and OHSU faculty involved in this research, including Jonah Sacha, Ph.D., have a significant financial interest in VIR Biotechnology Inc., a company that may have a commercial interest in the results of this research and technology.

All research involving animal subjects is reviewed and approved by a university’s Institutional Animal Care and Use Committee (IACUC). The IACUC’s priority is to ensure the health and safety of animal research subjects. The IACUC also reviews procedures to ensure the health and safety of the people who work with the animals. The IACUC conducts a rigorous review of all animal research proposals to ensure they demonstrate scientific value and justify the use of live animals.

The research was supported by the Bill & Melinda Gates Foundation Grand Challenges grant awards OPP1213553 and National Institute of Allergy And Infectious Diseases of the National Institutes of Health award R01AI40888; with support from the Office of the Director of the National Institutes of Health award P51OD011092 to the Oregon National Primate Research Center at OHSU. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation or the National Institutes of Health.

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JOURNAL

Nature Communications

DOI

10.1038/s41467-024-50345-6 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Cytomegalovirus vaccine vector-induced effector memory CD4+ T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza

ARTICLE PUBLICATION DATE

19-Jul-2024

COI STATEMENT

In the interest of ensuring the integrity of our research and as part of our commitment to public transparency, OHSU actively regulates, tracks and manages relationships that our researchers may hold with entities outside of OHSU. In regard to this research, OHSU and OHSU faculty involved in this research, including Jonah Sacha, Ph.D., have a significant financial interest in VIR Biotechnology Inc., a company that may have a commercial interest in the results of this research and technology.

 

Marshall University awarded grant to further fentanyl addiction research

MARSHALL UNIVERSITY JOAN C. EDWARDS SCHOOL OF MEDICINE

HUNTINGTON, W.Va. – Marshall University was awarded a $3.3 million grant (#R01DA057931) from the National Institute on Drug Abuse (NIDA) to examine the genetic mechanisms that underlie fentanyl addiction.  

In 2022, fentanyl overdose was the leading cause of death for U.S. adults aged 18 to 45, according to Families Against Fentanyl (2023).  

“This alarming statistic highlights the urgent need to understand why some people are more susceptible to fentanyl addiction,” said Price E. Dickson, Ph.D., assistant professor of biomedical sciences at the Marshall University Joan C. Edwards School of Medicine and lead investigator of this five-year study. “Identifying how certain genes influence the brain’s response to fentanyl will pave the way for the development of effective treatments, thus addressing a critical public health need.” 

According to the incentive sensitization theory of addiction, repeated drug use can make the brain’s reward system overly sensitive to drug-related cues, leading to a powerful craving for the drug. While both fentanyl addiction and incentive sensitization are known to be highly inheritable in humans and mice, the specific genetic mechanisms linking incentive sensitization to fentanyl addiction have remained elusive.  

Dickson and his team will use a panel of genetically diverse mice in concert with advanced neurogenomics and neuroscience approaches to discover the genes and brain mechanisms that underlie vulnerability and resistance to fentanyl addiction. Co-investigators Brandon J. Henderson, Ph.D., and Alejandro Q. Nato Jr. Ph.D., both associate professors of biomedical sciences at Marshall University, will bring expertise in neuroscience, bioinformatics and statistical genetics. 

Ultimately, this pioneering research may result in the development of novel, more effective addiction treatments and, in so doing, address a critical need in public health.  

An R01 research grant is a prestigious funding mechanism through the National Institutes of Health and its affiliated institutes and centers that supports health-related research projects. Securing this highly competitive grant signifies recognition of the project's scientific merit and its potential impact on advancing medical knowledge and improving public health. 

ABOLISH PRISONS

University of Cincinnati study examines impact of incarceration on youth health

College of Nursing researcher works to uncover health outcomes for children and families

Peer-Reviewed Publication

UNIVERSITY OF CINCINNATI

 

IMAGE: 

SAMANTHA BOCH, PHD, SHOWN IN THE UNIVERSITY OF CINCINNATI COLLEGE OF NURSING.

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CREDIT: COURTESY OF THE UNIVERSITY OF CINCINNATI

Researcher Samantha Boch has studied the impact of incarceration on child and family health for more than a decade.

Her latest research examines the health records and health care use of youth, individuals under age 21, who likely have been involved or whose families have been involved in the justice system. The challenge was identifying youth who have been impacted by mass incarceration, as most health care systems don’t routinely ask about incarceration. Families may not disclose that information due to stigma, fear of child protective services involvement, or judgment.

“There are few, if any, large community-level studies about the health of youth affected by incarceration, or their family’s incarceration, using medical records," explains Boch, an assistant professor at the University of Cincinnati College of Nursing. "Despite a lot of youth and families affected by incarceration, gaps remain in understanding its prevalence and consequences. There are numerous reasons for this, some include a lack of provider awareness, lack of curriculum in provider training, lack of funding for this research and lack of routine sensitive screening for exposure.”

Boch and her research team searched the electronic medical records for justice-related keywords such as “prison,” “jail,” “sentenced,” “probation,” “parole,” and others, to determine the impact of incarceration. The researchers used data from Cincinnati Children’s Hospital collected over an 11-year period.

Their study, published in Academic Pediatrics, found that of the more than 1.7 million records reviewed, 38,263 (or 2.2%) of youth seen between January 2009 and December 2020 likely had a parent incarcerated or faced some type of confinement as a juvenile. This small percentage was also responsible for a disproportionate number of physical and mental health diagnoses and health care visits at Cincinnati Children’s. They were compared against a socio demographically matched sample without a justice keyword and the total sample population of youth.

Nearly 63.3% of all behavioral health inpatient admissions, 23.7% of all hospitalization inpatient days and 45.5% of all foster care visits were attributed to the 2.2% of youth who had documented probable personal or family justice system involvement. The findings complement another study led by Boch, published in 2021 using data from Nationwide Children’s Hospital in Columbus, Ohio.

Youth with a justice keyword in their record had 1.5 to 16.2 times the prevalence of various physical and mental health disorder groupings studied compared to matched youth who didn't have a justice keyword but do have similar socioeconomic backgrounds. They also had 428.2 more physical health diagnoses and 269.2 more mental health diagnoses per 100 youth than the matched youth.

According to the study, youth with a justice keyword made up a large proportion of all of those who were diagnosed with health disorders or conditions at Cincinnati Children’s from 2009-2020. This includes 42.9% of all schizophrenia spectrum and other psychotic disorders, 42.1% of all bipolar and related disorders, 38.3% of all suicide and self-injury disorders, 24.5% of all trauma and stress related disorders, 44.9% of all shaken baby syndrome cases, 13.9% of all infectious diseases, 12.5% of speech language disorders and 12.8% of all youth pregnancies.

Nationally, about 7% of U.S. youth have had a parent incarcerated. Findings at Cincinnati Children’s and Nationwide Children’s Hospital in Columbus grossly underestimate the number of youth affected by incarceration or confinement, says Boch.

“Our data reflects families who disclosed and health providers who documented,” says Boch. “Families who refrain from disclosing or whose information is not documented were not represented which is a key limitation. This study is an attempt to uncover the size of the impact of mass incarceration on youth health in Cincinnati. Our health care systems and correctional systems clearly overlap and impact the lives of children. 

“Replication of these findings in other communities would strengthen the growing justification for decarceration efforts and other reforms, especially if we want all U.S. children and families to thrive,” says Boch. “We will continue to have health care disparities and lead the world with poor health outcomes if we continue to lead in incarceration.”

Other co-authors of the study include Joshua Lambert, PhD, University of Cincinnati; Christopher Wilderman, PhD, Duke University; and Judith Dexheimer, PhD; Robert Kahn, MD; and Sarah Beal, PhD, all of the University of Cincinnati and Cincinnati Children’s.

The research study of Cincinnati youth was supported by Boch’s awards, including the Agency for Healthcare Research and Quality and Patient Centered Outcomes Research Institute (AHRQ/PCORI) K12 PEDSnet Scholars Learning Health Systems Career Development Program, internal funding from the University of Cincinnati College of Nursing Dean’s New Investigator Award, internal funding from the Cincinnati Children’s Hospital Medical Center James M. Anderson Center for Health Systems Excellence, and the NIH/NIMHD Loan Repayment Award for Clinician Scientists from Disadvantaged Backgrounds. 

Read about Dr. Boch's research online.

 

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JOURNAL

Academic Pediatrics

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Pediatric Health and System Impacts of Mass Incarceration, 2009–2020: A Matched Cohort Study

 

Digital games on vaping devices could lure more youth to nicotine addiction

Like other smart devices, smart vapes have high-definition animated displays

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - RIVERSIDE

RIVERSIDE, Calif. -- In an “Industry Watch” research paper in the journal Tobacco Control, two scientists at the University of California, Riverside, raise the alarm on new electronic cigarette products equipped with touch screens, animated displays, and built-in games. Because the products are user friendly and attractive to youth, they may couple nicotine addiction with gaming disorder, the researchers caution.

Of particular concern to the researchers is that coupling nicotine to existing youth behaviors, such as video gaming and screen time use, could broaden the smart electronic cigarette market to include youth with no prior interest in nicotine products, while also reinforcing nicotine addiction among current users.

“Our lab is constantly monitoring the electronic cigarette market for new devices, especially ones that target youth and young adults,” said Man Wong, first author of the paper and an assistant in the lab of Prue Talbot, a professor of the graduate division. “One of these devices, Craftbox V-Play, can run Pac-Man, Tetris, and F22 — classic arcade games. Other devices that we found alarming were vapes that had digital games that encourage users to vape, vapes with animations that change as users puff, vapes that have built-in bluetooth and can be customized with personal photos, and vapes with celebrity endorsements that offer promotional trading cards.”

Talbot stressed that it is critical to pay attention to shifting trends in vape designs, especially disposable vapes that are user friendly and popular among youth. 

“Disposable vapes were relatively simple two years ago, and functioned as nicotine delivery devices,” she said. “Now they are designed to resemble and include features of smart phones and handheld gaming devices. These features make vapes more attractive to youth.”

Talbot and Wong believe the new devices need to be closely monitored and regulated. They report that unlike prior versions of electronic cigarettes, smart vapes prey on three potential addictions: nicotine dependence, gaming disorder, and screen time obsession. Talbot and Wong hope their research will encourage the Food and Drug Administration and other government agencies to regulate the sales of these devices. 

“In the long-term, increasing awareness of how vapes can evolve in short periods of time can increase surveillance and monitoring to ensure products that are targeting youth are swiftly removed from the market,” Talbot said. “More strict regulation can be put into place to restrict some features of vapes, and it may even be appropriate to push for a disposable vape ban altogether, as some countries have.”

The researchers were surprised to learn that some smart vapes had games requiring the user to vape to progress in the games, potentially accelerating nicotine addiction. For example, they found the “URSA Pocket,” a refillable pod-system, has three built-in games.

“One game contains a virtual pet, which you feed with coins that you acquire by vaping; another game counts your puffs and has leaderboards, which you can submit your rankings to social media for a chance to win prizes,” Wong said. “CB15K is a vape endorsed by a celebrity and offers trading cards when you purchase the device. The trading cards have a scannable QR code and the message ‘scan for a chance to win.’ The vape also has a display that has animations when the user puffs the device and is built in with wireless charging. These features can entice youth to purchase and use vapes.”

The researchers are concerned that many of the devices are affordable, around $15-20 each, which could entice youth to purchase them. 

“This is roughly the same price as, or cheaper than, the price of PUFF BARs or ELFBARs when they dominated the market,” Wong said. “These new products, however, offer much more puffs, higher power, and smart features for a lower price. A majority of the new disposable vapes come with many advanced functions. Regulation has not kept up with vapes at the rate they are evolving, and youth are vulnerable to these devices. In addition, disposable vapes create a lot of waste as they are one-time-use products, and adding screens, bluetooth, and digital storage to these devices exacerbates the waste generated by vapes.”

The research was supported by grants from the National Institute of Environmental Health Sciences of the National Institutes of Health, the Food and Drug Administration, and the Center for Tobacco Products.

The research paper is titled “Pac-Man on a vape: electronic cigarettes that target youth as handheld multimedia and gaming devices.”

The University of California, Riverside is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment is more than 26,000 students. The campus opened a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual impact of more than $2.7 billion on the U.S. economy. To learn more, visit www.ucr.edu.

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JOURNAL

Tobacco Control

DOI

10.1136/tc-2024-058794 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Pac-Man on a vape: electronic cigarettes that target youth as handheld multimedia and gaming devices

ARTICLE PUBLICATION DATE

15-Jun-2024

COI STATEMENT

No competing interests declared.