Duke-NUS research discovery sparks hope: Zika virus vaccine emerges as an unlikely hero in battling brain cancer

• The scientists discovered that Zika virus vaccine strains eradicate brain tumour cells while sparing healthy ones

Peer-Reviewed Publication

DUKE-NUS MEDICAL SCHOOL

 

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FROM RIGHT, ASSISTANT PROFESSOR ANN-MARIE CHACKO, ASSISTANT PROFESSOR ALFRED SUN, DR CARLA BIANCA LUENA VICTORIO AND PROFESSOR OOI ENG EONG WITH A CULTURE OF THEIR ZIKA VACCINE STRAINS

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CREDIT: DUKE-NUS MEDICAL SCHOOL

Scientists from Duke-NUS Medical School (Duke-NUS) have developed a new approach using the Zika virus to destroy brain cancer cells and inhibit tumour growth, while sparing healthy cells. Using Zika virus vaccine candidates developed at Duke-NUS, the team discovered how these strains target rapidly proliferating cells over mature cells—making them an ideal option to target fast-growing cancerous cells in the adult brain. Their findings, published in the Journal of Translational Medicine, potentially offer a new treatment alternative for brain cancer patients who currently have a poor prognosis.

Glioblastoma multiforme is the most common malignant brain cancer, with more than 300,000 patients diagnosed annually worldwide[i]. Survival rates for such patients are poor (around 15 months), mainly due to high incidence of tumour recurrence and limited treatment options. For such patients, oncolytic virotherapy—or the use of engineered viruses to infect and kill cancer cells—may address the current therapeutic challenges.

Zika virus is one such option in early development. The Duke-NUS team used Zika virus live-attenuated vaccine (ZIKV-LAV) strains, which are “weakened” viruses with limited ability to infect healthy cells but can still grow rapidly and spread within a tumour mass.

“We selected Zika virus because it naturally infects rapidly multiplying cells in the brain, allowing us to reach cancer cells that are traditionally difficult to target. Our ZIKV-LAV strains also replicate themselves in brain cancer cells, making this a living therapy that can spread and attack neighbouring diseased cells,” said Dr Carla Bianca Luena Victorio, first author of the paper and Senior Research Fellow at the Cancer & Stem Cell Biology Research Programme at Duke-NUS.

Dr Victorio and the team determined that ZIKV-LAV strains were highly effective in infecting cancer cells as these viruses bind to proteins that are present in high levels only in cancer cells and not in healthy cells. Upon infecting a cancer cell, these virus strains hijack the cell’s resources to reproduce, ultimately killing the cell. As the cancer cell’s protective membrane ruptures upon death, it releases its contents, including virus progeny that can infect and kill neighbouring cancer cells. In addition, some cellular proteins released from the infected cells  can activate an immune response to further inhibit tumour growth.

Through their experiments, the team observed that infection from ZIKV-LAV strains caused 65 to 90 per cent of glioblastoma multiforme tumour cells to die. While the ZIKV-LAV strains also infected 9 to 20 per cent of cells from blood vessels in the brain, the infection did not kill these healthy cells. In contrast, the original parent Zika virus strain killed up to 50 per cent of healthy brain cells.

The scientists also discovered that the ZIKV-LAV strains were not able to reproduce well even when they managed to infect healthy cells. The amount of virus measured in healthy brain cells infected with ZIKV-LAV was only 0.36 to 9 times higher than before infection. In contrast, the amount of virus in brain cancer cells infected with ZIKV-LAV was 100 to a billion times higher than before infection. This further illustrates that conditions in cancer cells are significantly more conducive for virus reproduction than in normal cells.

“Since the Zika virus outbreak in 2016, understandably, there has been fear about the nature of the virus and its devastating effects. Through our work, we hope to present the Zika virus in a new light by highlighting its potential to kill cancer cells. When a live virus is attenuated, such that it is safe and effective to fight infectious diseases, it can be beneficial to human health—not just as a vaccine but also as a potent tumour-eradicating agent,” said Assistant Professor Ann-Marie Chacko from Duke-NUS’ Cancer & Stem Cell Biology Research Programme. She is also the senior author of the paper.

The live attenuated virus strains were originally developed as a vaccine by Professor Ooi Eng Eong's group from Duke-NUS’ Emerging Infectious Diseases Research Programme. As a control, the virus strains were also tested on brain neurons or nerve cells that had been cultivated from human stem cells by Assistant Professor Alfred Sun’s team from the Neuroscience & Behavioural Disorders Research Programme in Duke-NUS. This provides a reliable screening tool to assess the safety and efficacy of using the virus as therapy in human cells.  

Asst Prof Chacko’s group is improving these and other Zika virus strains to increase their potency in killing not only brain cancer cells, but other types of cancer cells as well, while making them safer for use in patients. They are also modifying the virus so it can be imaged non-invasively after it has been injected into a patient. This will allow doctors to monitor where the virus goes in the patient and how long it is functional in the tumour.

To this end, the group is exploring commercialising their virus strains as both a Zika vaccine and treatment for brain cancer, and potentially other cancers, such as ovarian cancer.

Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, said: “This is a sterling example of how different research programmes within the School come together to tap their various expertise to advance medical knowledge and improve patients’ lives. The team’s valuable insights may one day translate into a new treatment option to control tumour growth or even, offer a cure for cancer.”

 

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Reference: Victorio, C.B. et al. (2024) ‘Repurposing of zika virus live-attenuated vaccine (ZIKV-LAV) strains as oncolytic viruses targeting human glioblastoma multiforme cells’, Journal of Translational Medicine, 22(1). doi:10.1186/s12967-024-04930-4.

 

 

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[i] Fan, Y., Zhang, X., Gao, C. et al. Burden and trends of brain and central nervous system cancer from 1990 to 2019 at the global, regional, and country levels. Arch Public Health 80, 209 (2022). https://doi.org/10.1186/s13690-022-00965-5.

 

About Duke-NUS Medical School                    

Duke-NUS is Singapore’s flagship graduate entry medical school, established in 2005 with a strategic, government-led partnership between two world-class institutions: Duke University School of Medicine and the National University of Singapore (NUS). Through an innovative curriculum, students at Duke-NUS are nurtured to become multi-faceted ‘Clinicians Plus’ poised to steer the healthcare and biomedical ecosystem in Singapore and beyond. A leader in ground-breaking research and translational innovation, Duke-NUS has gained international renown through its five Signature Research Programmes and ten Centres. The enduring impact of its discoveries is amplified by its successful Academic Medicine partnership with Singapore Health Services (SingHealth), Singapore’s largest healthcare group. This strategic alliance has spawned 15 Academic Clinical Programmes, which harness multi-disciplinary research and education to transform medicine and improve lives.   

For more information, please visit www.duke-nus.edu.sg 

  

Cultured human neurons infected with ZIKV-LAV. Infection in pink and cell nuclei in blue.

CREDIT

Duke-NUS Medical School

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JOURNAL

Journal of Translational Medicine

DOI

10.1186/s12967-024-04930-4 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Repurposing of Zika virus live-attenuated vaccine (ZIKV-LAV) strains as oncolytic viruses targeting human glioblastoma multiforme cells

 

Researchers develop artificial building blocks of life

Peer-Reviewed Publication

UNIVERSITY OF COLOGNE

 

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STRUCTURAL COMPARISON OF DNA AND THE ARTIFICIAL TNA, A XENO NUCLEIC ACID WITH THE NATURAL BASE PAIRS AT AND GC AND AN ADDITIONAL BASE PAIR (XY).

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CREDIT: STEPHANIE KATH-SCHORR

The DNA carries the genetic information of all living organisms and consists of only four different building blocks, the nucleotides. Nucleotides are composed of three distinctive parts: a sugar molecule, a phosphate group and one of the four nucleobases adenine, thymine, guanine and cytosine. The nucleotides are lined up millions of times and form the DNA double helix, similar to a spiral staircase. Scientists from the UoC’s Department of Chemistry have now shown that the structure of nucleotides can be modified to a great extent in the laboratory. The researchers developed so-called threofuranosyl nucleic acid (TNA) with a new, additional base pair. These are the first steps on the way to fully artificial nucleic acids with enhanced chemical functionalities. The study ‘Expanding the Horizon of the Xeno Nucleic Acid Space: Threose Nucleic Acids with Increased Information Storage’ was published in the Journal of the American Chemical Society.

Artificial nucleic acids differ in structure from their originals. These changes affect their stability and function. “Our threofuranosyl nucleic acid is more stable than the naturally occurring nucleic acids DNA and RNA, which brings many advantages for future therapeutic use,” said Professor Dr Stephanie Kath-Schorr. For the study, the 5-carbon sugar deoxyribose, which forms the backbone in DNA, was replaced by a 4-carbon sugar. In addition, the number of nucleobases was increased from four to six. By exchanging the sugar, the TNA is not recognized by the cell's own degradation enzymes. This has been a problem with nucleic acid-based therapeutics, as synthetically produced RNA that is introduced into a cell is rapidly degraded and loses its effect. The introduction of TNAs into cells that remain undetected could now maintain the effect for longer.  “In addition, the built-in unnatural base pair enables alternative binding options to target molecules in the cell,” added Hannah Depmeier, lead author of the study.  Kath-Schorr is certain that such a function can be used in particular in the development of new aptamers, short DNA or RNA sequences, which can be used for the targeted control of cellular mechanisms. TNAs could also be used for the targeted transport of drugs to specific organs in the body (targeted drug delivery) as well as in diagnostics; they could also be useful for the recognition of viral proteins or biomarkers.

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JOURNAL

Journal of the American Chemical Society

DOI

10.1021/jacs.3c14626 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Expanding the Horizon of the Xeno Nucleic Acid Space: Threose Nucleic Acids with Increased Information Storage

ARTICLE PUBLICATION DATE

8-Mar-2024

 

U-M researchers open new leads in anti-HIV drug development, using a compound found in nature

Peer-Reviewed Publication

UNIVERSITY OF MICHIGAN

A team of University of Michigan researchers has successfully modified a naturally occurring chemical compound in the lab, resulting in advanced lead compounds with anti-HIV activity.

 

Their results, published March 7 in the Journal of Medicinal Chemistry, offer a new path forward in the development of drugs that could potentially help cure—rather than treat—HIV.

 

Although effective treatments are available to manage HIV, a cure has remained elusive due to the virus's ability to hide from the immune system, lying dormant in reservoirs of infected cells.

 

"With most viruses, when people get infected, they get sick for a while and then the immune system kicks in and the virus is cleared," said Kathleen Collins, professor of microbiology and immunology at the U-M Medical School. "But with HIV, once a patient is infected, that virus will persist for their entire life—meaning they must remain on treatments indefinitely."

 

One key to HIV's ability to remain hidden in patients' cells is a protein that the virus makes, called Nef. This protein shuts down a system that the cell would normally use to alert the immune system to an infection, thus preventing the immune cells from recognizing and clearing the virus.

 

Collins and her lab have studied this protein for more than 15 years, investigating how it works and how it can be disabled. She and David Sherman, professor at the U-M Life Sciences Institute, previously discovered that a chemical found in nature can inhibit HIV Nef, allowing the immune system to find and eliminate virally infected cells: a compound called concanamycin A (CMA), which is produced by a soil-derived microorganism.

 

In its natural form, however, CMA presents several challenges as a potential therapeutic. The first challenge the team had to overcome was supply. While CMA is a naturally occurring compound, the original bacteria that produces it does so in quantities far too small to be useful for testing and modification in the lab.

 

Another major challenge with developing CMA as an anti-HIV drug is that Nef is not CMA's primary target.

 

"CMA's main job in human cells is to inhibit an enzyme called V-ATPase, which we absolutely do not want to block in this case," said Sherman, who is also a professor at the U-M College of Pharmacy, Medical School, and College of Literature, Science, and the Arts. "So, we needed to find a way to modify CMA's activity, widening the effective dosage gap between when it starts to inhibit the target we're aiming for—HIV Nef — without affecting V-ATPase, its typical cellular target."

 

With this latest research, the team has overcome both of these challenges. Using bioengineering, Sherman's team was able to develop a bacterial strain that increased CMA production 2,000-fold. Synthetic chemists in the lab then created more than 70 new variations of the compound, swapping out different chemical groups, to test for their potency against HIV Nef.

 

Collins' lab team ran the new compounds through a battery of tests to measure their toxicity to cells, as well as how they affected the activities of both HIV Nef and V-ATPase.

 

"Even though we know that CMA is extremely active against the HIV Nef protein, all drugs have side effects," said Collins, also a professor of internal medicine at the Medical School. "And so we wanted to ensure we've done everything we can to minimize the side effect profile of the drug before we consider putting it into an animal or human."

 

The team now has several CMA analogs that show high potency in blocking HIV Nef at very low dosage levels, without interrupting off-target effects or causing toxicity in human cells. They caution, however, that several important steps remain before the compounds would be ready for further testing in a clinical setting.

 

"We are really encouraged, though, because our groups have solved some very important problems," Sherman said. "We have engineered microorganisms to produce sustainable supplies of the natural product molecules and have really good chemical methods to make new analogs. And we have the methodologies in place to continue tracking the critical toxicity and potency parameters to further reduce off-target effects."

 

The research was supported by the National Institutes of Health.

 

Other study authors are: Morgan McCauley, Matthew Huston, Alanna Condren, Filipa Pereira, Joel Cline, Marianne Yaple-Maresh, Mark Painter, Gretchen Zimmerman, Andrew Robertson, Nolan Carney, Christopher Goodall and Valeri Terry of U-M and Rolf Müller of Hemholtz Institute for Pharmaceutical Research, Germany.

 

Study: Structure-activity relationships of natural and semisynthetic plecomacrolides suggest distinct pathways for HIV-1 immune evasion and vacuolar ATPase-dependent lysosomal acidification (DOI: 10.1021/acs.jmedchem.3c01574)

 

Written by Emily Kagey, U-M Life Sciences Institute

 

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JOURNAL

Journal of Medicinal Chemistry

DOI

10.1021/acs.jmedchem.3c01574 

 

Socially prescribed creative play boosts parents’ and children’s wellbeing

Peer-Reviewed Publication

UNIVERSITY OF LEEDS

University of Leeds news 

For immediate release 

Socially prescribed creative play boosts parents’ and children’s wellbeing 

Socially prescribed creative play helps children and their parents develop new skills and promotes wellbeing, a new study has found. 

The University of Leeds-led study evaluated a five-week programme of arts-based play, including singing and music-making, for families of children aged up to three. It found that parents benefited from developing social networks and sharing experiences with each other, as well as learning creative approaches to parenting. The families also gained vital information about their child’s developmental milestones. 

The programme, which was developed by leading children’s arts charity Theatre Hullabaloo to address concerns about parental wellbeing following the pandemic, is the first known socially prescribed creative play intervention for families with children of this age.  

Social prescription is an approach enabling health professionals to refer people in need of help to address their health and wellbeing for non-medical support like local group activities. It can be an effective alternative to medication or other interventions. 

Study author Dr Paige E. Davis, Lecturer in Developmental Psychology in the University of Leeds’ School of Psychology, said: “Social prescription is usually thought to be focused on older and elderly individuals. Recently there has been a push to facilitate different life transitions through social prescription. The transition to parenthood has been neglected in the past in terms of support offered, despite the importance of the relationship between parent and child in the first 1,001 days.” 

“Our study shows that social prescribing for parents and children has benefits for both. Parents believe it improves their wellbeing, while giving them opportunities to build social networks and learn new ways to play creatively. Parents also perceive that it improves their children’s ability to develop new skills.” 

Miranda Thain, Artistic Producer at Theatre Hullabaloo, said: “We see the positive effects of playing creatively with your little one and feeling confident to use those skills in your parenting - whether it be reading, singing or music making - in our work with families every day. Social prescription provides an important route for families who might need extra support and care to take part in programmes of this type.  

“This research, which demonstrates the value in terms of the wellbeing of both parent and child, is hugely important as we make the case for better investment in early years creativity, giving families the tools to be the best they can be for each other.” 

The programme consisted of a one-hour session which had a clear, yet flexible structure. Activities included sensory and imaginary play installations, play stations with age-appropriate toys, books and sensory activities, and more structured ‘Sing and Play’ sessions followed by ‘independent creative play’ time, where children played together while their parents were offered a hot drink. Each session culminated with gentle live music played on the flute and ukulele, sensory lights, bubbles, lullabies and a goodbye song.  

Parents noted key differences between the sessions and typical play groups, which they said could be chaotic and overwhelming. The same group of people attended the study sessions week on week, which parents said was better for developing new connections than typical playgroups, which are open to one-off drop-ins. 

Especially important to parents was their trust in the prescribers and organisation, and the sense of calm that the intervention fostered, because this enabled them to be receptive to practical parenting knowledge and new social relationships.  

Parents believed that the socially prescribed creative play positively impacted their children’s development and their own mental health and knowledge. 

Further research is needed to evaluate the longer-term impact on children’s development and the interactions between parents and their children, the authors say. 

Further information 

“My Favourite Part was Learning Different ways to Play; Evaluating a Socially Prescribed Creative Play Programme” is published in Public Health journal on 8 March 2023. 

Email University of Leeds press officer Lauren Ballinger on l.ballinger@leeds.ac.uk with media enquiries. 

University of Leeds  

The University of Leeds is one of the largest higher education institutions in the UK, with more than 38,000 students from more than 150 different countries. We are renowned globally for the quality of our teaching and research.  

We are a values-driven university, and we harness our expertise in research and education to help shape a better future for humanity, working through collaboration to tackle inequalities, achieve societal impact and drive change.   

The University is a member of the Russell Group of research-intensive universities, and plays a significant role in the Turing, Rosalind Franklin and Royce Institutes. www.leeds.ac.uk   

Follow University of Leeds or tag us in to coverage: Twitter | Facebook | LinkedIn | Instagram 

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JOURNAL

Public Health

DOI

10.1016/j.puhe.2024.01.032 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

My favourite part was learning different ways to play: qualitatively evaluating a socially prescribed creative play programme

ARTICLE PUBLICATION DATE

8-Mar-2024

 

Limited correlation between canine lymphoma and proximity to environmental toxins in new study

Peer-Reviewed Publication

MORRIS ANIMAL FOUNDATION

 

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ASHLEIGH TINDLE, A RESEARCHER INVOLVED IN THE PROJECT AND A PH.D. STUDENT AT THE UNIVERSITY OF WISCONSIN-MADISON, STANDS WITH A POSTER ON HER PROJECT, WHICH EVALUATED THE LINK BETWEEN FRACKING AND RADON AND CANINE CANCER.

 

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CREDIT: LAUREN TREPANIER

DENVER/March 8, 2024 – As awareness of the health risks associated with radon and fracking exposure in connection to cancer continues to rise in human medicine, a recent study explored these ties with multicentric lymphoma, a prevalent canine cancer. Surprisingly, the study did not identify significant correlations between living near sources of environmental toxins, such as fracking by-products and radon, and dogs diagnosed with lymphoma.   

The results of this study were published on Monday using data from Morris Animal Foundation’s Golden Retriever Lifetime Study, which enrolled dogs with multicentric lymphoma and matched unaffected dogs. Using special geospatial software, the researchers mapped the dogs’ home addresses to U.S. Environmental Protection Agency radon zones and active fracking wells.  

Ashleigh Tindle, a researcher involved in the project and a Ph.D. student at the University of Wisconsin-Madison, expressed surprise at the lack of correlation, given similar connections found in children with leukemia living near fracking sites. Acknowledging the study's limitations due to the small sample size and the lack of fracking wastewater data for some states, Tindle emphasized the study’s role as an initial step in exploring the available information.   

The study focused on county-level information over a decade but did not have data on individual home radon levels, which is a significant limitation. Additionally, the enrolled dog population was biased toward those who can afford veterinary care and seek a definitive diagnosis, while fracking wells tend to be near lower-income areas.  

The research team recommends follow-up studies, including direct measurements of radon emissions and volatile organic compounds, which are pollutants generated by vehicle exhaust and industrial activities, and fracking in the homes of dogs with lymphoma. The team’s next project involves analyzing urine and blood samples from the Study to understand how VOCs and herbicide exposures could alter a dog’s DNA, potentially creating a biomarker of later lymphoma development. 

“The next steps are to connect the dots between dogs that are exposed to environmental chemicals and whether there is evidence of DNA damage or other early hallmarks of cancer risk that could lead to lymphoma,” Tindle said.  

About Morris Animal Foundation  
Morris Animal Foundation’s mission is to bridge science and resources to advance the health of animals. Founded in 1948 and headquartered in Denver, it is one of the largest nonprofit animal health research organizations in the world, funding nearly $160 million in more than 3,000 critical animal health studies to date across a broad range of species. Learn more at morrisanimalfoundation.org.  

Media Contact: Annie Mehl 

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JOURNAL

Journal of Veterinary Medicine

ARTICLE TITLE

Environmental radon, fracking wells, and lymphoma in dogs

ARTICLE PUBLICATION DATE

8-Mar-2024

 

Pushing the boundary on ultralow frequency gravitational waves

Lowest-ever frequency gravitational waves spotted in pulsar data

Peer-Reviewed Publication

UNIVERSITY OF FLORIDA

A team of physicists has developed a method to detect gravity waves with such low frequencies that they could unlock the secrets behind the early phases of mergers between supermassive black holes, the heaviest objects in the universe.

The method can detect gravitational waves that oscillate just once every thousand years, 100 times slower than any previously measured gravitational waves.

“These are waves reaching us from the farthest corners of the universe, capable of affecting how light travels,” said Jeff Dror, Ph.D., an assistant professor of physics at the University of Florida and co-author of the new study. “Studying these waves from the early universe will help us build a complete picture of our cosmic history, analogous to previous discoveries of the cosmic microwave background.”

Dror and his co-author, University of California, Santa Cruz postdoctoral researcher William DeRocco, published their findings Feb. 26 in Physical Review Letters.

Gravitational waves are akin to ripples in space. Like sound waves or waves on the ocean, gravitational waves vary in both frequency and amplitude, information that offers insights into their origin and age. Gravitational waves that reach us can be oscillating at extremely low frequencies, much lower than those of sound waves detectable with the human ear. Some of the lowest frequencies detected in the past were as low as one nanohertz.

“For reference,” Dror explained, “the frequency of sound waves created by an alligator roar are about 100 billion times higher than this frequency – these are very low-pitched waves.”

Their new method of detection is based on analyzing pulsars, neutron stars that emit radio waves at highly regular intervals. Dror hypothesized that searching for gradual slowdown in the arrivals of these pulses could reveal new gravitational waves. By studying existing pulsar data,  Dror was able to search for gravitational waves with lower frequencies than ever before, increasing our “hearing range” to frequencies as low as 10 picohertz, 100 times lower than previous efforts that detected nanohertz-level waves.

While gravitational waves with frequencies around a nanohertz have been detected before, not much is known about their origin. There are two theories. The leading idea is that these waves are the result of a merger between two supermassive black holes, which, if true, would give researchers a new way to study the behavior of these giant objects that lie at the heart of every galaxy.

The other main theory is that these waves were created by some sort of cataclysmic event early in the universe’s history. By studying gravitational waves at even lower frequencies, they may be able to differentiate these possibilities.

“Looking ahead, the next step is to analyze newer data sets,” Dror said. “The datasets we used were primarily from 2014 and 2015, and a huge number of pulsar observations have been undertaken since that time.”

Dror also plans to run simulations on mock data using UF’s HiPerGator supercomputer to further unravel cosmic history. The supercomputer can efficiently run large, complex simulations, significantly reducing the time required to analyze data.

This study was supported in part by the National Science Foundation and the Department of Energy.

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JOURNAL

Physical Review Letters

DOI

10.1103/PhysRevLett.132.101403 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Using Pulsar Parameter Drifts to Detect Subnanohertz Gravitational Waves

ARTICLE PUBLICATION DATE

8-Mar-2024

 

Primary care scarcity linked to more surgical emergencies & problems

Worse outcomes for patients living in rural and urban areas with few primary care providers suggests need to boost efforts to increase training and geographic distribution

Peer-Reviewed Publication

MICHIGAN MEDICINE - UNIVERSITY OF MICHIGAN

America’s shortage of primary care doctors and nurse practitioners has a downstream effect in the nation’s operating rooms, a new study finds. 

And patients suffer as a result. 

In all, people living in areas with the most severe shortages of primary care providers have a much higher risk of having emergency surgery, rather than a scheduled operation,

 compared with people with the same condition who live in areas with less-dire primary care shortages.Those living in the areas with the lowest availability of primary care providers also have a higher chance of suffering complications after surgery, and needing to go back to the hospital after they’ve left it, according to the findings in the journal Health Affairs from a team at Michigan Medicine, the University of Michigan’s academic medical center. 

The team looked at data for people with traditional Medicare coverage who had operations for conditions where timing can really matter: colectomy to remove a cancerous area of the colon, repair of a hernia, and repair of aneurysms in wall of the aorta, the body’s largest blood vessel. 

They focused only on people living in areas classified by the federal government as having a shortage of primary care providers. They then divided these areas into five levels of shortage. 

In all, nearly 38% of the patients living in the more-severe shortage areas had their operations on an emergency basis, compared with 30% of those living in the areas with the least-severe shortages. 

Those living in areas with more severe shortages also had a higher risk of serious complications from surgery (15% vs. nearly 12%), and those living in the most severe shortage areas also had a higher risk of readmission to the hospital (nearly 16% vs. 13.5%). 

Lead author Sara Schaefer, M.D., said her experience growing up in Idaho and going to medical school at the University of Washington -- where she learned alongside primary care providers serving huge rural areas -- informed her interest in the topic. She is now a resident in the U-M Department of Surgery and a healthcare administration fellow at the Center for Healthcare Outcomes and Policy, and notes that she and her colleagues operate on many patients who travel from rural areas of Michigan, especially for emergency operations. 

“The primary care provider shortage is a key piece in accessing care, because if you have no access to primary care, that impacts your access to specialists,” she said. “A scheduled surgical case is always better than an emergency case in outcomes, costs and impact on the patient’s life, so the role of the primary care provider in identifying a potential issue, and referring a patient for diagnostic imaging and surgery, can make a major difference in addressing an urgent problem before it becomes an emergency.” 

While she and her colleagues on the study – including surgery assistant professor Andrew Ibrahim, M.D., M.Sc. – did not show a difference in patients’ risk of death based on severity of primary care shortage, they did show that mortality risk was lower for those living in non-shortage areas compared with shortage areas. 

The results of the study, the authors say, should underscore the importance of efforts to increase the supply of primary care providers and to attract them to practice in underserved areas. 

This includes both rural and urban primary care shortage areas; the study found that 58% of the census tracts classified as having a primary care shortage of any level were rural. 

Loan forgiveness and restructuring programs, to alleviate the education-related debt of physicians and other providers, are a key tool in this effort, Schaefer notes. Encouraging more providers to choose primary care careers, rather than specializing, and incentivizing them to practice in areas of shortage, could ultimately mean better outcomes when people living in those areas need time-sensitive operations, even if they travel many miles to get to the operating room. 

The study does not include data on people covered by Medicaid, VA or private insurance, but Schaefer hopes other researchers will attempt to duplicate the findings in those populations. 

In the meantime, she says, the message to people living in shortage areas is to seek out a primary care provider to have as a regular source of care, even if getting an appointment takes a while because of shortages. And, she says, don’t ignore new symptoms; instead, know how to escalate a concern with your regular provider. 

For surgeons, she said, the realization that some of their patients having urgent or emergency surgery might be doing so because they don’t have access to a regular primary care provider is an important one. 

“Use the post-surgery hospitalization as a time to intervene and facilitate contact with a primary care provider who can assist with recovery and with other health issues the patient may be facing,” she said. “The role of the primary care doctor as a partner in care of our surgical patients cannot be overstated.”

In addition to Schaefer and Ibrahim, who is a member of the U-M Institute for Healthcare Policy and Innovation, the authors of the study are CHOP fellow and Surgery resident Shukri H. A. Dualeh, M.D., CHOP statistician Nicholas Kunnath, M.S., and John W. Scott, M.D., M.P.H., formerly of U-M and now at the University of Washington.

The study was funded by the National Institutes of Health (CA236621) and the Agency for Healthcare Research and Quality

Higher Rates Of Emergency Surgery, Serious Complications, And Readmissions In Primary Care Shortage Areas, 2015–19, Health Affairs, DOI:10.1377/hlthaff.2023.00843 

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JOURNAL

Health Affairs

DOI

10.1377/hlthaff.2023.00843 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Higher Rates Of Emergency Surgery, Serious Complications, And Readmissions In Primary Care Shortage Areas, 2015–19

ARTICLE PUBLICATION DATE

8-Mar-2024

 

The brain builds emotions regardless of the senses

In a new study, researchers at the IMT School for Advanced Studies Lucca deciphers the interplay of emotion and perception.

Peer-Reviewed Publication

IMT SCHOOL FOR ADVANCED STUDIES LUCCA

How much do our emotions depend on our senses? Does our brain and body react in the same way when we hear a fearful scream, see an eerie shadow, or smell a sinister odor? And does hearing an upbeat music or seeing a colorful landascape bring the same joy?

In an innovative study published in Science Advances, researchers have unveiled new insights into the intricate relationship between emotion and perception.

Led by a team of Italian neuroscientists from the IMT School for Advanced Studies Lucca, and conducted in collaboration with the University of Turin, the research project investigates whether the brain employs sensory-specific or abstract codes to construct emotional experiences.

"Emotion and perception are deeply intertwined, yet the exact mechanisms by which the brain represents emotional instances have remained elusive," says Giada Lettieri, researcher in psychology at the IMT School, and lead author of the study. "Our research addresses this fundamental question, providing critical insights into how the brain organizes and represents emotional information across different sensory modalities and as a result of past sensory experience."

To conduct the study, the researchers showed the movie 101 Dalmatians to a group of 50 volunteers, and tracked with functional magnetic resonance imaging the brain activity associated with the unfolding of the movie plot. The viewers of the movie in the scanner were both individuals with typical development and congenitally blind and congenitally deaf volunteers, who were presented with the audio play and the silent version of the movie, respectively. The researchers also asked a group of 124 independent participants to express and rate their emotions while watching the same movie outside the scanner, trying to predict the brain response of people with and without sensory deprivation during the experience of amusement, fear, and sadness, among other emotions.

“Including in the experiment individuals with congenital sensory deprivation – blind and deaf people – is a way to dissect and decipher the contribution of sensory experience to neural mechanisms underlying emotions” explains Luca Cecchetti, researcher at the IMT School, and senior author and supervisor of the study. “Our results show that emotions categories are represented in the brain regardless of sensory experience and modalities. In particular, there is a distributed network encompassing sensory, prefrontal, and temporal areas of the brain, which collectively encode emotional instances. Of note, the ventromedial prefrontal cortex emerged as a key locus for storing an abstract representation of emotions, which does not depend on prior sensory experience or modality."

The existence of an abstract coding of emotions in the brain signifies that even though we are tempted to believe that our emotions directly depend on what happens in the surrounding world, it is our brain that is wired to generate emotional meaning regardless of whether we are able to see or hear.

"In a world where sensory-deprived individuals are frequently overlooked, it is essential to understand how mental faculties and their corresponding neural representations can evolve and refine without sensory input, so to further advance the understanding of the emotion and the human brain," says Lettieri.

 

 

 

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JOURNAL

Science Advances

DOI

10.1126/sciadv.adk6840 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Dissecting abstract, modality-specific and experience-dependent coding of affect in the human brain

ARTICLE PUBLICATION DATE

8-Mar-2024