Having explored how the heart is formed in utero, a University of Houston pharmacology researcher is reporting how cells and molecules act during that early formation and what might cause the heart disease called left ventricular non-compaction. LVNC is a type of heart muscle disease (or cardiomyopathy) also known as a spongy heart, for which patients often require heart transplants.
“We found the absence of a certain gene, called Itgb1, may cause inability in the developing heart to maintain its shape and develop normally, causing left ventricular non-compaction,” reports Mingfu Wu, associate professor at the UH College of Pharmacy, in Cardiovascular Research. “Itgb1 deletion at an early stage causes distinct defects.”
Wu’s findings involve examination of the trabeculae, which are sheet-like structures in developing hearts that protrude from the heart wall. These structures are crucial in early heart development — before the coronary system develops — to supply blood, as they increase the inner surface area of the heart wall and enhance the exchange of oxygen and nutrients between blood and the heart wall.
“Without trabeculae, the heart wall would suffer from insufficient oxygen and nutrients, potentially leading to death. Conversely, an excess of trabeculae can result in an overly porous heart wall, leading to left ventricular non-compaction cardiomyopathy, commonly known as spongy heart,” said Wu.
While certain signals controlling trabeculae formation are known, the precise mechanisms by which individual cells that make up the cardiac muscle (cardiomyocytes) are organized to form these structures remain unclear.
“This study reveals that deleting a gene called Itgb1 in heart wall cardiomyocytes prevents trabeculae formation. We found that the protein β1 integrin encoded by Itgb1 and its ligands, the extracellular matrix, create a molecular network that acts as a scaffold for cardiomyocytes in the heart wall. When Itgb1 is deleted, cardiomyocytes disengage from this scaffold, losing their ability to maintain shape, divide properly, migrate, and form trabeculae,” said Wu.
The study suggests that the molecular network may be a common organizational mechanism in organ formation.
“We believe these insights will greatly interest researchers in organ development and regeneration, potentially reshaping our understanding of tissue organization and development,” said Wu.
Wu’s collaborators from the University of Houston include Lianjie Miao, Yangyang Lu, Anika Nusrat, Luqi Zhao Micah Castillo, Yongqi Xiao, Hongyang Guo, Yu Liu, Preethi Gunaratne, Robert, J Schwartz, Alan R Burns, Ashok Kumar and C. Michael DiPersio, Albany Medical College.

A new study has found that patients diagnosed with schizophrenia or another psychotic disorder are three times more likely to have Bartonella DNA in their blood than adults without these disorders. The work further supports the idea that pathogens — particularly vector-borne pathogens — could play a role in mental illness.
Bartonella are a group of vector-borne bacteria transmitted primarily via arthropods like fleas, lice and potentially ticks, but also by the animals that harbor them. For example, the species Bartonella henselae is associated with cat scratch disease, which until recently was thought to be a short-lived (or self-limiting) infection. There are at least 45 different known Bartonella species, of which 18 have been found to infect humans.
Improved methods for detecting Bartonella infection in animals and humans have led to the diagnosis of bartonelloses in patients with a host of chronic illnesses, as well as in some patients with psychiatric symptoms.
In this latest study, researchers at North Carolina State University analyzed the blood of 116 people for evidence of Bartonella DNA and Bartonella specific antibodies. The samples were collected during a biomarker research study conducted by Dr. Shannon Delaney and colleagues at the Columbia University Irving Medical Center (CUIMC).
Of the 116 people, 29 were in the control group; 16 were prodromal, meaning they had symptoms but no formal diagnosis; 51 were children, adolescents or adults with psychosis; and 20 were close relatives of those diagnosed with psychosis.
In a previous study conducted at Columbia, these same patients had been tested for increased inflammatory mediators — in other words, evidence of inflammation. That study found that patients with psychosis were more likely to have increased inflammatory markers in the blood.
“As an infectious disease researcher, I believe that infection should be critically examined as a potential cause of diseases for which the cause is unclear or unknown,” says Dr. Edward Breitschwerdt, Melanie S. Steele Distinguished Professor of Internal Medicine at NC State’s College of Veterinary Medicine. “We wanted to explore potential drivers of inflammation in patients with neuropsychiatric illnesses. Based on the associations I’ve seen between Bartonella and symptoms of mental illness in my prior work, Bartonella infection could be one possible candidate.”
In a blinded study, the NC State team used immunofluorescence assays and digital droplet PCR testing to detect and amplify DNA in the blood samples. As the blood samples had been frozen and stored, the researchers did not attempt to culture bacteria from them. Culturing the bacteria can further enhance DNA detection.

Forty-three percent of participants diagnosed with psychosis had Bartonella DNA in their blood compared to 14% in the control population. Additionally, using DNA sequencing, the team was able to identify the Bartonella species for 18 of the 31 participants with Bartonella in their blood, including infection or co-infection with Bartonella henselae (11/18), Bartonella vinsonii subsp. berkhoffii (6/18), Bartonella quintana (2/18), Bartonella alsatica (1/18), and Bartonella rochalimae (1/18)
This is the second study to identify Bartonella in the blood of psychiatric patients. A 2020 study, interrupted by the COVID pandemic, found Bartonella species DNA in 11 of 17 (65%) University of North Carolina School of Medicine patients with schizophrenia versus one of 13 (8%) in healthy volunteer controls.
“We’ve now demonstrated the presence of Bartonella species in the blood of two separate cohorts of patients with neuropsychiatric symptoms, which indicates that these bacteria are worth studying further as a potential driver of these symptoms,” Breitschwerdt says. “At the very least, we need to continue to see if these findings are replicated in other patient populations.”
“This study provides further support for an association between Bartonella species infection and psychosis and may have important clinical implications,” notes Dr. Brian Fallon of CUIMC. “However, it is worth emphasizing that association does not prove causality; other factors may account for the association.
“The other significant finding was that the frequency of positive antibody tests for Bartonella infection was not significantly different for the controls versus the individuals with psychosis; this suggests that exposure to Bartonella is common in the general population and that reliance on serologic test results alone can be misleading.”
The study appears in Frontiers in Psychiatry and was supported in part by the Steven & Alexandra Cohen Foundation, the Lyme & Tick-borne Diseases Research Center at CUIMC, and the American Academy of Child and Adolescent Psychiatry. Dr. Delaney is first author. Cynthia Robveille, assistant research professor at NC State, is co-first author. Drs. Breitschwerdt and Fallon are co-corresponding authors. Other NC State co-authors include Research Professor Ricardo Maggi, former Ph. D. student Dr. Erin Lashnits, junior research scientist Emily Kingston, and graduate research assistant Chance Liedig. Research RN Lilly Murray from Columbia University also contributed to the work.

If national guidelines are revised to incorporate a new risk equation, about 40% fewer people could meet criteria for cholesterol-lowering statins to prevent heart disease, according to a study by researchers at the University of Pittsburgh, Beth Israel Deaconess Medical Center and University of Michigan. Published today in JAMA Internal Medicine, the study examines the potential impact of widespread adoption of the PREVENT equations, which were released by the American Heart Association in November 2023 to update physicians’ go-to calculators for assessing patients’ 10-year risk of heart attack or stroke.
At a population level, the number of adults recommended for statins could decrease from 45.4 million to 28.3 million. At the same time, the study showed that most people who would be recommended to take statins are not currently taking them.
“This is an opportunity to refocus our efforts and invest resources in the populations of patients at the highest risk,” said lead author Dr. Timothy Anderson, M.D., M.A.S., a primary care physician at UPMC and health services researcher and assistant professor of medicine at Pitt.
For their analysis, the team used nationally representative data from 3,785 adults, ages 40 to 75, who participated in the National Health and Nutrition Examination Survey from January 2017 to March 2020. The researchers estimated 10-year risk of atherosclerotic cardiovascular disease (ASCVD) using the Predicting Risk of cardiovascular disease EVENTs (PREVENT) equations and compared the results to risk estimated using the previous tool, known as Pooled Cohort Equations (PCE). The PREVENT equations were developed by the American Heart Association to more accurately represent risk across the current U.S. population, as the PCE equations were based on patient data that were decades old and lacked diversity.
PREVENT also reflects more recent insights into the biology of ASCVD. Current statin use as well as metabolic and kidney diseases are incorporated into the new calculation, while race has been removed from it, reflecting a growing awareness that race is a social construct.
Using PREVENT, the team found that among the study’s entire cohort, 10-year risk of developing ASCVD was 4%, half as high as the risk calculated by the PCE (8%). The difference was even larger for Black adults (5.1% versus 10.9%) and for adults between the ages of 70 and 75 (10.2% versus 22.8%).
An estimated 4.1 million patients who are currently taking statins would no longer be recommended to take them based on PREVENT. For these patients and their physicians, clear and careful communication is key, said Anderson. “We don’t want people to think they were treated incorrectly in the past. They were treated with the best data we had when the PCE was introduced back in 2013. The data have changed.”
At the same time, it’s important to note that everyone’s risk will inevitably change over time, as well, he added. “For a patient who we now know is at lower risk than we previously thought, if we recommend they stop taking statins, they still could be back to a higher risk five years down the road, for the simple reason that everybody’s risk goes up as we get older.”
Other authors on the study were Linnea Wilson, M.P.H., of Beth Israel Deaconess Medical Center, and Jeremy B. Sussman, M.D., M.P.H., of University of Michigan, Ann Arbor.
This research was supported by the National Institute on Aging (#K76AG074878).

General anesthesia makes it possible for millions of patients each year to undergo lifesaving surgeries while unconscious and free of pain. But the 176-year-old medical staple uses powerful drugs that have stoked fears of adverse effects on the brain — particularly if used in high doses.
New findings published June 10 in the Journal of the American Medical Association (JAMA), however, support an earlier study that indicates that anesthesia is no more hazardous for the brain at higher doses than at lower doses, according to the researchers.
The new study reports results of a multicenter clinical trial of more than 1,000 older patients who underwent cardiac surgery at four hospitals in Canada. Researchers at these hospitals, in partnership with colleagues at Washington University School of Medicine in St. Louis, found that the amount of anesthesia used during surgery did not affect the risk of postoperative delirium — a state that may contribute to long-term cognitive decline.
“Concern that general anesthesia harms the brain and causes both early and lasting postoperative cognitive disorders is a major reason that older adults avoid or delay life-enhancing procedures,” said Michael S. Avidan, MBBCh, the Dr. Seymour and Rose T. Brown Professor of Anesthesiology and head of the Department of Anesthesiology at Washington University. “Our new study contributes to other compelling evidence that higher doses of general anesthesia are not toxic to the brain. Dispelling the misleading and pervasive message that general anesthesia causes cognitive disorders will have major public health implications by helping older adults make wise choices regarding essential surgeries, which will promote and sustain healthier lives.”
The dose of administered anesthesia historically has been a carefully calculated balance between too little and too much. Administering an inadequate amount puts patients at risk of experiencing intraoperative awareness. Despite advances in anesthesia care, about 1 in 1,000 people still experience unintended waking during surgery without being able to move or indicate their pain or distress. This can lead to suffering and lifelong emotional trauma.
“The good news is that the distressing complication of intraoperative awareness can be more reliably prevented,” said Avidan, the study’s senior author. “Anesthesia clinicians can now confidently administer a sufficient dose of general anesthesia, providing a margin of safety for unconsciousness, without being concerned that this will put their patients’ brains at risk. The practice of general anesthesia should change based on mounting reassuring evidence.”
Previous smaller studies have suggested that too much anesthesia could be to blame for postoperative delirium, a neurological problem involving confusion, altered attention, paranoia, memory loss, hallucinations and delusions, among other symptoms. A common postoperative complication affecting about 25% of older patients after major surgeries, delirium can be distressing to patients and family members. It is typically temporary but has been linked to longer intensive care and hospital stays, other medical complications, persistent cognitive decline and higher risk of death.

To study the impact of minimizing anesthesia on postoperative delirium, Avidan and colleagues previously conducted a similar clinical study in more than 1,200 older surgical patients at Barnes-Jewish Hospital in St. Louis. The researchers used an electroencephalogram (EEG) to monitor electrical activity in the brains of patients during major surgery and adjusted anesthesia levels to prevent brain activity suppression, considered a sign of excessive anesthesia levels. They found that minimizing anesthesia administration did not prevent postoperative delirium.
To expand upon the results of their single-hospital clinical trial, Avidan collaborated with Alain Deschamps, MD, PhD, a professor of anesthesiology at Universitè de Montreal in Montreal, and a team of Canadian clinical researchers, to conduct the multicenter trial involving patients at four hospitals in Canada — in Montreal, Kingston, Winnipeg and Toronto.
This randomized clinical trial enrolled 1,140 patients undergoing cardiac surgery, high-risk procedures with a high rate of postoperative complications. Roughly half of the patients had their anesthesia adjusted based on electrical activity in the brain, and the other group of patients received the usual care without EEG monitoring. The former group was exposed to almost 20% less anesthesia than the latter group and also had 66% less time with suppressed electrical brain activity, but in both groups, 18% of the patients experienced delirium in the first five days after surgery. Additionally, the length of hospital stays, the incidence of medical complications and the risk of death up to one year postoperatively were no different between patients in the two study groups. However, almost 60% more patients in the group that received less anesthesia had undesirable movements while their surgeons were operating, which could have negatively affected the surgeries.
“The thinking has been that deep general anesthesia excessively suppresses electrical brain activity and causes postoperative delirium,” Avidan said. “Taken together, our two clinical trials, including almost 2,400 high-risk older surgical patients at five hospitals in the United States and Canada, dispel the concern that higher general anesthetic dosing incurs a neurotoxic cost. Delirium is likely to be caused by factors other than general anesthesia, such as the pain and inflammation associated with surgery. Future research should explore other avenues to prevent postoperative delirium. But we can now confidently reassure our patients that they can request and expect to be oblivious, immobile and pain-free during surgical procedures, without worrying about general anesthesia damaging their brains.”

By super cooling a molecule on the surface of brain cells down to about minus 180 degrees Celsius — nearly twice as cold as the coldest places in Antarctica — scientists at Johns Hopkins Medicine say they have determined how a widely-used epilepsy drug works to dampen the excitability of brain cells and help to control, although not cure, seizures.
The research, published June 4 in Nature Structural & Molecular Biology, identifies critical connections between activity of the epilepsy drug perampanel and the resulting movements of the AMPA receptor — a brain cell surface molecule. The researchers say the findings could eventually help with designing new drugs that target the receptor to treat other neurological conditions such as Alzheimer’s disease, schizophrenia, learning disabilities, brain cancers called glioblastoma and chronic pain.
The AMPA receptor plays a critical role for one of the brain’s most abundant neurotransmitters — glutamate — which activates brain cells (neurons) by connecting with a protein on the cell surface (AMPA) in a Pac-man-like connection, in which AMPA receptors engulf glutamate.
Up to four glutamate molecules can bind to a single AMPA receptor. The connection enables a flood of ions (positively-charged particles) to enter the neuron and activate (excite) it.
“AMPA receptors and glutamate are necessary for most aspects of life, including the processes of learning, memory and encoding experiences,” says Edward Twomey, Ph.D., assistant professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine. “Most neurological diseases trace back in some way to AMPA receptors and glutamate.”
Twomey was approached by neuroscientist Richard Huganir, Ph.D., who has been studying AMPA receptors for 40 years, to collaborate on research to better understand the receptors’ structure and their glutamate binding process.
Overactivation (excitation) of AMPA receptors is known to cause epilepsy. Perampanel, which targets the AMPA receptor, is the only medicine approved by the U.S. Food and Drug Administration to target AMPA receptors, but many pharmaceutical companies are working on similar compounds, the researchers say.

“This drug was initially discovered in the 1980s, and its precise mechanism has been a long standing mystery,” says Twomey.
“We know that this drug doesn’t block or get stuck in the receptor’s ion channels,” says Huganir, Bloomberg Distinguished Professor of Neuroscience and Psychological and Brain Sciences and director of the Solomon H. Snyder Department of Neuroscience. Other scientists had found where perampanel binds to AMPA receptors in pockets around the ion channel but had not found the way that connection disrupts ion flow.
To study the mechanism, the researchers turned to cryo-electron microscopy (cryoEM), which has evolved in the last two decades as a powerful tool to study structures a million times smaller than the width of a human hair.
Johns Hopkins postdoctoral fellow W. Dylan Hale, Ph.D., working in the Twomey and Huganir labs, performed most of the experiments and analysis in the Beckman Center for CryoEM at Johns Hopkins, where they super chill biological molecules and take images at various timepoints.
For the study, the researchers analyzed millions of images of AMPA receptors in brain cells from mice and rat models and their interaction with the originally discovered version of the perampanel drug, GYKI-52466. “These interactions happen at a super tiny scale, about 1 to 2 angstroms,” says Twomey. An angstrom is 1 10 billionth of a meter.
They looked at the GYKI-52466 drug’s binding, with and without glutamate. They also performed electrical recordings of the ion flow, and physiology studies in mice to complement the cryoEM images.

The scientists used artificial intelligence and machine learning tools to average and combine the cryoEM images into a 3D reconstruction of the receptor.
When glutamate binds to the AMPA receptor in one of four positions, a strand of the receptor comes down and pulls open the ion channel enabling the flow of ions, akin to how a pull chain releases water from a shower head.
The researchers found that two of the four glutamate binding positions are the most important in the GYKI-52466 drug’s ability to block the ion flow.
“The drug binds to the AMPA receptor and prevents the ion channel from opening by blocking the ability of glutamate to pull on the strand that opens the ion channel,” says Twomey. “It seems to decouple the glutamate binding regions from each other and put the receptor into a desensitized state.”
Huganir also plans to work with Twomey to use cryoEM to study what happens to the AMPA receptor when it’s mutated.
“We want to know what’s wrong with the receptor’s structure that disables its function,” Huganir says. “In theory, we could develop drugs to make the receptor more active to treat conditions in which the receptor’s structure is altered.”
In addition to Hale, Twomey and Huganir, researchers who contributed to the work are Alejandra Montaño Romero and Albert Lau at Johns Hopkins, and Cuauhtemoc Gonzalez and Vasanthi Jayaraman at the University of Texas Health Science Center at Houston.
Funding support for the study was provided by the Searle Scholars Program, the Diana Helis Henry Medical Research Foundation, and the National Institutes of Health (R37 NS036715, R01 GM094495, R35 GM122528, F99NS130928, K99 MH132811).

Adolescents who experience higher levels of social anxiety symptoms are more likely to report increased suicidal thoughts and other depressive symptoms two years later, according to new research.
The University of East Anglia-led study sheds light on the pressing need for early interventions to address society anxiety in young people.
Lead author Dr Kenny Chiu, Clinical Lecturer in Clinical Psychology at UEA’s Department of Clinical Psychology and Psychological Therapies, said: “Social Anxiety Disorder (SAD) often begins during adolescence, manifesting as intense fear and discomfort in social situations.
“This study provides valuable insights into how social anxiety symptoms may convey risks to developing other important mental health issues if left unaddressed.”
Second author Prof Argyris Stringaris, Professor of Child and Adolescent Psychiatry at University College London, said: “Our findings suggest addressing social anxiety early could be crucial in preventing the development of suicidal thoughts and other depressive symptoms.”
Depressive symptoms one year into the study also partially explained the connection between early social anxiety and later depressive symptoms.
Last author Dr Eleanor Leigh, MRC Clinician Scientist Fellow at University of Oxford and Honorary Associate Professor at University College London, said: “Our findings highlight that social anxiety plays a significant role in the persistence of depressive symptoms in adolescents.”
The study builds on a meta-analytic review led by Dr Eleanor Leigh, Dr Kenny Chiu, and Dr Elizabeth Ballard, which highlighted the lack of longitudinal research looking at the relationship between social anxiety and suicidal thoughts in adolescents.

The study analysed data from the Wellcome Trust Neuroscience in Psychiatry Network (NSPN) 2,400 cohort dataset.
This accelerated longitudinal study recruited more than 2,400 young people aged between 14 and 24 from London and Cambridgeshire areas between 2012 and 2017.
Participants were assessed over a two-year period, once at the outset, another a year later, and the final one at the end of two years.
Dr Chiu said: “Such a discovery would not have been possible without the NSPN consortium, which provides robust data accessible to child and adolescent mental health researchers.”
The study was funded by The Wellcome Trust Neuroscience in Psychiatry Network (NSPN) and was a collaboration between UEA, University College London and the University of Oxford.

Researchers have for the first time demonstrated that a specific class of oxide membranes can confine, or “squeeze,” infrared light — a finding that holds promise for next generation infrared imaging technologies. The thin-film membranes confine infrared light far better than bulk crystals, which are the established technology for infrared light confinement.
“The thin-film membranes maintain the desired infrared frequency, but compress the wavelengths, allowing imaging devices to capture images with greater resolution,” says Yin Liu, co-corresponding author of a paper on the work and an assistant professor of materials science and engineering at North Carolina State University.
“We’ve demonstrated that we can confine infrared light to 10% of its wavelength while maintaining its frequency — meaning that the amount of time that it takes for a wavelength to cycle is the same, but the distance between the peaks of the wave is much closer together. Bulk crystal techniques confine infrared light to around 97% of its wavelength.”
“This behavior was previously only theorized, but we were able to demonstrate it experimentally for the first time through both the way we prepared the thin-film membranes and our novel use of synchrotron near-field spectroscopy,” says Ruijuan Xu, co-lead author of the paper and an assistant professor of materials science and engineering at NC State.
For this work, the researchers worked with transition metal perovskite materials. Specifically, the researchers used pulsed laser deposition to grow a 100-nanometer thick crystalline membrane of strontium titanate (SrTiO3) in a vacuum chamber. The crystalline structure of this thin film is high quality, meaning that it has very few defects. These thin films were then removed from the substrate they were grown on and placed on the silicon oxide surface of a silicon substrate.
The researchers then made use of the technology at the Advanced Light Source of the Lawrence Berkeley National Laboratory to perform synchrotron near-field spectroscopy on the strontium titanate thin film as it was exposed to infrared light. This enabled the researchers to capture the interaction of the material with infrared light at the nanoscale.
To understand what the researchers learned, we need to talk about phonons, photons and polaritons. Phonons and photons are both ways that energy travels through and between materials. Phonons are essentially the waves of energy caused by how atoms vibrate. Photons are essentially the waves of electromagnetic energy. You can think of phonons as units of sound energy, whereas photons are units of light energy. Phonon polaritons are quasi particles that occur when an infrared photon is coupled with an “optical” phonon — meaning a phonon that can emit or absorb light.

“Theoretical papers proposed the idea that transition metal perovskite oxide membranes would allow phonon polaritons to confine infrared light,” Liu says. “And our work now demonstrates that the phonon polaritons do confine the photons, and also keep the photons from extending beyond the surface of the material.
“This work establishes a new class of optical materials for controlling light in infrared wavelengths, which has potential applications in photonics, sensors and thermal management,” Liu says. “Imagine being able to design computer chips that could use these materials to shed heat by converting it into infrared light.”
“The work is also exciting because the technique we’ve demonstrated for creating these materials means that the thin films can be easily integrated with a wide variety of substrates,” Xu says. “That should make it easy to incorporate the materials into many different types of devices.”
The research was done with support from the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering, under contract no. DE-AC02-76SF00515; and by the National Science Foundation under grant number 2340751.

Checkpoint immunotherapy utilizing PD-1 blockade has become the standard of care for metastatic melanoma. While this treatment is effective in 40 percent of patients, the other 60 percent develop resistance, leading to tumor regrowth. A multidisciplinary research team led by the University of California, Irvine has identified a new strategy that could enhance the therapeutic effectiveness of this therapy by targeting the communication between immune cells within the tumor.
In a study published online today in the journal Cancer Cell, researchers demonstrate that while PD-1 blockade activates a potent antitumor response in CD8+ T cells, it also promotes the accumulation of T regulatory cells, decreasing the immune response against the tumor. The activation of these competing signals — one set combatting the tumor and the other restraining the immune system — is likely a significant challenge in providing effective cancer treatment.
“Our latest research reveals that CD8+ T cells, activated by PD-1 blockade to target melanoma, also interact with T regulatory cells, which subsequently dampen the immune response against the tumor,” said corresponding author Francesco Marangoni, UC Irvine assistant professor of physiology & biophysics. “We analyzed the intricate dynamics of communication between CD8+ T and T regulatory cells, which are analogous to two telephone landlines connected by a cable. If we cut the cable, the CD8+ T cells won’t be able to ‘call’ the T regulatory cells and instruct them to inhibit the immune response to the cancer.”
Team members focused on the mechanism of communication between CD8+ T and T regulatory cells in tumors and identified a pivotal role for a molecule called ICOS, which is required for T cell activation. They found that by neutralizing ICOS and PD-1, CD8+ T cells increased their activity against the tumor but could no longer stimulate T regulatory cells.
“Our work helped identify a reason why some patients treated with checkpoint blockade develop resistance to it,” said first author Shannon Geels, a UC Irvine graduate student researcher in the Department of Physiology & Biophysics. “We found that communication between cells can lead to immunotherapy failure and that we can improve efficacy by interrupting specific messages exchanged by immune cells.”
The next phase of this research involves understanding the complex communication network among various cell types in a tumor.
“We do not think there is only one ‘phone cable’ to cut,” Marangoni said. “Our findings provide a promising pathway to increasing our understanding of communication among all cell types within a tumor. This will enable us to identify the messages that block the full potential of CD8+ T cells stimulated by PD-1 blockade so that we can maximize the benefit to patients.”
Other UC Irvine team members included faculty and graduate students from the physiology & biophysics, biological chemistry, dermatology and developmental & cell biology departments; the Institute for Immunology; the Center for Complex Biological Systems; and the NSF-Simons Center for Multiscale Cell Fate Research; as well as faculty from Saint John’s Cancer Institute in Santa Monica; the University of Alabama at Birmingham; and Massachusetts General Hospital and Harvard Medical School.
This work was supported by pilot grants from the Chao Family Comprehensive Cancer Center, the National Science Foundation, the U.S. Department of Defense and the National Institutes of Health, among others.

Agents from various federal agencies will focus on unauthorized candy-flavored and nicotine-laden vapes that have flooded the U.S. market from overseas.A multi-agency coalition of law enforcement agents will begin tackling the unruly market of illegal e-cigarettes, under pressure from antismoking groups, lawmakers and the tobacco industry urging federal authorities to stop the flood of vaping devices favored by adolescents.The Justice Department announced the new effort, which is expected to target fruit- and candy-flavored vapes containing high levels of addictive nicotine.The new coalition would include the Bureau of Alcohol, Tobacco, Firearms and Explosives; the U.S. Marshals Service; the Federal Trade Commission and the U.S. Postal Service, tapping into federal laws that could include significant fines and jail terms. “Unauthorized e-cigarettes and vaping products continue to jeopardize the health of Americans — particularly children and adolescents — across the country,” Benjamin C. Mizer, the acting associate attorney general, said.Until now, enforcement efforts have largely involved warning letters and limited penalties issued by the Food and Drug Administration to various vendors like gas station and convenience store owners, ordering them to stop selling the items.Those F.D.A. initiatives have been criticized as unsuccessful by congressional lawmakers and others, who have pushed the agency to do more to keep illegal e-cigarettes from entering the United States.Traditional tobacco companies, including Reynolds American, have also asked the F.D.A., which regulates tobacco, to banish the illicit products that are in competition with their own e-cigarettes. Their call for flavored vape enforcement, though, has ended at the U.S. border. British American Tobacco, Reynolds’ parent company, has said it marketed its Vuse Go vapes in flavors like Mango Ice and Blue Raspberry in 46 countries.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Five years on the Phoenix streets battered Vance Blair’s body. His vision dimmed, his speech slowed, and his hands began to twitch. A bulging pelvis revealed the need for hernia surgery, and the vacant lot where he slept was no place to keep dressings clean.Mr. Blair often lingered by a shaded building, and several women who worked there grew fond of the diffident man who asked permission to escape the sun. They brought him food and discovered his dilemma: Medicaid would cover his operation, but hospitals discharge patients quickly and surgeons would not proceed unless he had a place to heal.Then they learned that a Phoenix group runs what amounts to a nursing home for the homeless. Mr. Blair has remained there since his operation six months ago and says the care might have saved his life.“After a while of being outside, I was having thoughts of not wanting to live anymore,” he said. “This place has been a great help.”Respite care for homeless people is rapidly growing, aimed at people well enough to leave the hospital but too sick for the street. Its rise reflects the aging of the unhoused population and the decade-long expansion of Medicaid, which helps cover the cost. Many programs also get subsidies from hospitals or insurance companies eager to shorten hospital stays or reduce readmissions.The number of programs, mostly nonprofit, has roughly doubled since 2016, to more than 165, according to the National Institute for Medical Respite Care. The movement has spread to places like Memphis; Missoula, Mont.; and Greenville, S.C., underscoring the ubiquity of homelessness.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.