Publisher Health

While blood clotting is important to prevent blood loss and for our immunity, coagulation also can cause health issues and even death. Currently, one in four people worldwide dies from diseases and conditions caused by blood clots. Meanwhile, anticoagulants used to reduce risks can also cause significant issues, such as uncontrolled bleeding.
Now, a new biomolecular anticoagulant platform invented by a team led by UNC Charlotte researcher Kirill Afonin holds promise as a revolutionary advancement over the blood thinners currently used during surgeries and other procedures. The team’s discoveries are reported in the journal Nano Letters, first available online on July 5.
“We envision the uses of our new anticoagulant platform would be during coronary artery bypass surgeries, kidney dialysis, and a variety of vascular, surgical and coronary interventions,” Afonin said. “We are now investigating if there are potential future applications with cancer treatments to prevent metastasis and also in addressing the needs of malaria, which can cause coagulation issues.”
The paper shares the most recent results from three years of collaboration among researchers with the Frederick National Laboratory for Cancer Research (Nanotechnology Characterization Laboratory), University of São Paulo in Brazil, The Pennsylvania State University, and Uniformed Services University of the Health Sciences.
“All this resulted in a massive international and interdisciplinary effort to develop a completely new technology that we think may revolutionize the field and be picked up by other areas of health research,” Afonin said.
The team’s technology turns to programmable RNA-DNA anticoagulant fibers that, when injected into the bloodstream, form into modular structures that communicate with thrombin, which are the enzymes in blood plasma that cause blood to clot. The technology allows the structures to prevent blood clotting as it is needed, then be swiftly eliminated from the body by the renal system once the work is done.

Adding erythropoietin to cooling therapy for term newborns with birth asphyxia has no benefit over cooling therapy alone, a study published today in the New England Journal of Medicine.
The findings contrast with results from small trials in which erythropoietin appeared safe and effective, noted Dr. Sandra “Sunny” Juul, senior author of the study. The Alan Hodson Endowed Professor of Pediatrics at the UW School of Medicine, Juul is also the UW Medicine chief of neonatology (newborn medical care) and practices at Seattle Chldren’s.
Hypoxic ischemic encephalopathy occurs when too little oxygen is going to the brain and other vital organs at or near time of birth. The multicenter trial of 500 infants with moderate or severe hypoxic ischemic encephalopathy found an equal risk of death or neurodevelopmental impairment at 2 to 3 years of age for the placebo group that received hypothermia treatment only, and the hypothermia plus erythropoietin group.
In addition, the study showed an unexpected finding. The erythropoietin group had more serious adverse events during the newborn period than the placebo group.
“It’s a negative outcome, but this is important for clinicians to know,” said Juul. “This study demonstrates how important large prospective randomized controlled trials are. These larger phase III studies have enough statistical power to truly answer a clinical question. The larger study size also was able to demonstrate the unexpected safety concern.”
This does not mean that erythropoietin, or commonly called “epo,” doesn’t have possibilities as a therapeutic for hypoxic ischemic encephalopathy, she said. The drug may be beneficial in treating the hypoxic ischemic encephalopathy in low-resource counties, without the use of hypothermia as a treatment, or where cooling therapies are simply not available, she said.

A team of researchers, including LSU Health New Orleans Infectious Diseases and Microbiology professor Michael Hagensee, MD, PhD, has shown for the first time that treating precancerous anal growths called high-grade squamous intraepithelial lesions (HSILs) in persons living with HIV significantly decreased the progression to anal cancer. Results are published in the New England Journal of Medicine.
Like cervical cancer, anal cancer is caused by human papillomavirus (HPV), leading to precancerous high-grade squamous intraepithelial lesions that can progress to cancer.
“Treatment of high-grade cervical lesions is known to prevent cervical cancer in women,” notes Dr. Hagensee. “Anal cancer has Increased 25-fold in persons living with HIV, and the ANCHOR study is based on the same approach.”
The ANCHOR (Anal Cancer-HSIL Outcomes Research) trial enrolled more than 4,000 people living with HIV who had high-grade anal lesions on biopsy at 25 sites in the US.
“We screened over 300 people at University Medical Center and followed 100 with high-grade lesions,” says Dr. Hagensee, who sees patients at UMC, a major LSU Health New Orleans teaching hospital.
Participants were randomly assigned to a treatment group or a group who were closely observed, the current standard of care. Those in the treatment group underwent procedures to remove the lesions — office-based ablative procedures, ablation or excision under anesthesia — or the administration of topical fluorouracil or imiquimod. Treatment reduced anal cancer by 57%.
Although anal cancer is rare in the general population, with 9,440 new cases estimated in 2022, the incidence has been increasing in the US. The highest risk is for persons living with HIV.
“Our results support the use of screening and treatment for anal HSIL as the standard of care for persons living with HIV,” Dr. Hagensee concludes. “Next steps include determining the best way to screen persons living with HIV for detecting high-grade lesions, when should this screening start and at what intervals, and what is the best way to treat someone with high-grade anal lesions.”
The research was supported by the National Cancer Institute of the National Institutes of Health.
Story Source:
Materials provided by Louisiana State University Health Sciences Center. Note: Content may be edited for style and length.

The latest research from the labs of Penn scientists Paulo Arratia and Douglas Jerolmack was an answer to “a call for help,” says Arratia.
It was 2020, and the Philadelphia Orchestra, like so many cultural institutions, had suspended performances due to the COVID-19 pandemic. Through P.J. Brennan, chief medical officer of the University of Pennsylvania Health System, the Orchestra sought expertise to help understand whether its musicians could return to playing in a safe physical arrangement that would minimize the chances of exposing one another, or their audiences, to SARS-CoV-2.
“The Orchestra director didn’t want the musicians to be far apart; they needed to be close together to produce the best sound,” says Arratia, of the School of Engineering and Applied Science. “And yet, if they needed to be separated with plexiglass, that also posed a problem.” The musicians reported problems hearing one another and poor sightlines with plexiglass dividers. “The challenge was, how can we get away from this to the point where they can play unobstructed but still safely,” Arratia says.
Now, in a publication in Nature Communications, Arratia, Jerolmack, and colleagues report on their findings, which suggest the aerosols musicians produce dissipate within about six feet. The results not only informed the arrangement of the Philadelphia Orchestra as they resumed performances in the summer of 2020 but also laid the groundwork for how other musical groups might think about safely gathering and playing.
“Having experts like Paulo and Doug, who could measure particle size and trajectory and distance and velocity, were really valuable in making decisions for the orchestra,” says Brennan, who now serves on the Orchestra’s Board of Directors. “Those decisions included the spacing between players, the distancing between sections, who needed to mask. As they gathered this information, along with the testing and case tracking that Penn Medicine was doing, it helped us make decisions with confidence.”
Experimental approach
The research hinged on the questions of how many aerosol particles the musicians generated, how densely the particles were emitted from the instruments, and how fast they traveled through the air.

Antisense oligonucleotides, or ASOs, are molecules that can be used to control protein levels in cells. Cold Spring Harbor Laboratory Professor Adrian Krainer leveraged ASO technology to develop the first FDA-approved treatment for spinal muscular atrophy called Spinraza®. The drug has helped over 11,000 patients make more of a protein that certain neurons in the spine need.
Since then, Krainer has been searching for more ways ASOs can help treat other disorders. He has zeroed in on cystic fibrosis (CF), where patients do not make enough of a protein called CFTR. His team discovered how to use ASOs to make more of an imperfect but still functional version of CFTR. The discovery sets the stage for a new therapeutic approach that may help reduce CF symptoms and improve patients’ quality of life.
The imperfect CFTR protein is a result of a gene mutation. It causes cells to receive the wrong instructions for making the protein. The faulty instructions are eliminated and the protein isn’t made, since in general, imperfect proteins may be disruptive. Krainer’s ASOs trick cells into following the faulty instructions and making the imperfect CFTR protein. His team found that, in this case of CF, having an imperfect version of the protein is better than having none at all. Their method improved the function of lung cells, suggesting the ASO strategy could improve symptoms in CF patients with this mutation.
The team’s discovery spotlights a new way ASOs can be used to treat disease. The study was led by Young Jin Kim, a former M.D.-Ph.D. student in the Krainer laboratory. Krainer hopes to continue expanding the potential of ASO technology in therapeutics. He thinks in the future ASOs may increasingly become a way to tailor therapies specific to an individual’s unique genetic mutations. “If more of this type of drug, ASOs, are approved,” Krainer says, “I wouldn’t be surprised if in the not-so-distant future ASOs become a routine way to make personalized medicines.”
Story Source:
Materials provided by Cold Spring Harbor Laboratory. Original written by Luis Sandoval. Note: Content may be edited for style and length.

Air pollution is not just a problem for lungs. Increasingly, research suggests air pollution can influence childhood behavioral problems and even IQ. A new study led by the University of Washington has added evidence showing that both prenatal and postnatal exposure to air pollution can harm kids.
The study, published in Environmental Health Perspectives, found that children whose mothers experienced higher nitrogen dioxide (NO2) exposure during pregnancy, particularly in the first and second trimester, were more likely to have behavioral problems.
Researchers also reported that higher exposures to small-particle air pollution (PM2.5) when children were 2 to 4 years old was associated with poorer child behavioral functioning and cognitive performance.
“Even in cities like Seattle or San Francisco, which have a lot of traffic but where the pollution levels are still relatively low, we found that children with higher prenatal NO2 exposure had more behavioral problems, especially with NO2exposure in the first and second trimester,” said Yu Ni, lead author and a postdoctoral scholar in the Department of Environmental & Occupational Health Sciences.
The study involved data gathered from 1,967 mothers recruited during pregnancy from six cities: Memphis, Tennessee; Minneapolis; Rochester, N.Y.; San Francisco; and two in Washington, Seattle and Yakima. Originally, these participants were enrolled as part of three separate studies: CANDLE, GAPPS and TIDES. The three studies have been combined under a major NIH initiative called ECHO, which brings together multiple pregnancy cohorts to address key child health concerns. These three combined cohorts are known as the ECHO PATHWAYS consortium.
The study employed a state-of-the-art model of air pollution levels in the United States over time and space that was developed at the University of Washington. Using participant address information, the researchers were able to estimate each mother and child’s exposures during the pregnancy period and early childhood.
Exposure to NO2 and PM2.5 pollution in early life is important to understand, Ni said, because “there are known biological mechanisms that can link a mother’s inhalation of these pollutants to effects on placenta and fetal brain development.”
Furthermore, once the child is born, the first few years are a critical time of ongoing brain development as the number of neural connections explodes and the brain reaches 90% of its future adult size, the researchers write. For young children, inhaled pollutants that invade deep in the lung and enter the central nervous system can cause damage in areas relevant for behavioral and cognitive function.
“This study reinforces the unique vulnerability of children to air pollution — both in fetal life where major organ development and function occurs as well as into childhood when those processes continue. These early life perturbations can have lasting impacts on lifelong brain function. This study underscores the importance of air pollution as a preventable risk factor for healthy child neurodevelopment,” said senior author Dr. Catherine Karr, a professor in the UW School of Public Health and School of Medicine.
More specifically, the researchers found that exposure to PM2.5 pollution was generally associated with more behavioral problems in girls than in boys, and that the adverse effect of PM2.5 exposure in the second trimester on IQ was stronger in boys.
“We hope the evidence from this study will contribute to informed policymaking in the future,” Ni said. “In terms of reducing air pollution, the U.S. has gone a long way under the Clean Air Act, but there are threats to continued improvement in the nation’s air quality. The evidence suggests there is reason to bring the level of air pollution down even further as we better understand the vulnerability of pregnant women and children.”
Co-authors include Christine Loftus, Michael Young and Marnie Hazlehurst, UW Department of Environmental and Occupational Health Sciences; Sheela Sathyanarayana, UW School of Public Health and School of Medicine; Adam Szpiro, UW Department of Biostatistics; Laura Murphy, Frances Tylavsky and W. Alex Mason, University of Tennessee; Kaja LeWinn and Nicole Bush, University of California San Francisco; and Emily Barrett, Rutgers University. This research was funded by the National Institutes of Health through the ECHO-PATHWAYS consortium.
Story Source:
Materials provided by University of Washington. Original written by Jake Ellison. Note: Content may be edited for style and length.

Organ transplant recipients take life-long immunosuppressive drugs to prevent their bodies from mounting an immune response against the donated organ, yet a substantial number of them still reject the organs. A new study by researchers from the University of Chicago shows that transplant recipients also mount an immune response against commensal bacteria in the organ graft, adding to the immune response against the genetic makeup of the tissue and reducing the effectiveness of immunosuppressive drugs.
The study, published today in the Journal of Clinical Investigation, also shows that this anti-microbial immune response can be triggered by immune cell memory of previous encounters with bacteria, further complicating the body’s ability to accept a lifesaving new organ.
“Before, we thought the reason why transplanted organs in humans are less easily accepted than in sheltered laboratory animals is that humans can have immune memory responses that cross-react on the cells of the organ, and memory responses are more difficult to suppress with drugs than naïve responses,” said Maria-Luisa Alegre, MD, PhD, Professor of Medicine at UChicago and senior author of the study. “Now, we see that it’s not only memory cells that recognize the organ itself that are the problem, but also memory responses that recognize bacteria in the organ.”
Two separate immune responses
The success of organ transplants depends on the type of organ. Lungs and small intestines are notoriously difficult to transplant and have shorter survival times. Statistics show that within five years of surgery, 41% of lung and 54% of intestinal transplant recipients rejected their grafts, compared to organs like kidneys (just 27% rejection) and hearts (23%). One hypothesis was that lungs and intestines, but not kidneys and hearts, are exposed to microbes from the air and digestive system and that the organ recipients were mounting immune responses not only to the organs but also to the microbes in those organs.
In a previous study, Alegre and her team had shown that when mice received a skin graft colonized with Staphylococcus epidermidis (S. epi), a common bacteria found on the human skin, S. epi caused low grade inflammation in the graft. The team then wondered if the host mounted a separate immune response against the bacteria in the graft in addition to the more well-understood “alloresponse,” or reaction to the foreign cells in the tissue, and if both could damage the graft.
“The commensal bacteria in the graft are different from the commensal bacteria of the recipient because each individual harbors a unique set of microbes, so the host may also see these bacteria as foreign too,” Alegre said. “We thought that maybe these two separate immune responses (host-versus-transplant and host-versus-bacteria) could work additively or synergistically to mount a more robust immune response against the graft and explain why the half-life of the organs that have microbes is shorter.”
Dealing with a lifetime of immune memory
In the new study, the researchers used mice from UChicago’s gnotobiotic facility which were carefully raised in a sterile environment and not colonized by any microbe. The team transplanted skin from donor mice that were genetically identical to the recipients to avoid an alloresponse. The receiving mice mounted an immune T cell response against the graft when it was first colonized with S. epi, but not when it was left sterile. This immune response damaged the skin graft, but not very much.
Alegre and her team then tested if prior immune exposure to commensal bacteria would cause greater damage to a graft colonized by similar bacteria, so they infected some recipient mice with S. epi before transplanting them, letting them develop memory responses to the bacteria. When these mice later received a skin graft colonized with similar bacteria, the immune response was much stronger and significantly damaged the new tissue. This is significant because transplant patients already have a lifetime of exposure to many bacteria and other microbes through everyday cuts, scrapes, infections, and diet.
Most importantly, when they transplanted mice with skin grafts that were genetically different and colonized with bacteria — simulating the scenario like most human organ transplants — they saw that immunosuppressive drugs that prolonged transplant survival in naïve mice did not work in mice with anti-bacterial memory.
“That explains why when you transplant a lung or intestine, patients do less well and have to receive higher levels of immunosuppression than when you transplant sterile organs,” Alegre said. “You have to deal not only with the response against the graft, but also the response against the bacteria that come with the graft.”
Story Source:
Materials provided by University of Chicago. Original written by Matt Wood. Note: Content may be edited for style and length.

In a new proof-of-concept study led by Dr. Mark Walker at the University of Ottawa’s Faculty of Medicine, researchers are pioneering the use of a unique Artificial Intelligence-based deep learning model as an assistive tool for the rapid and accurate reading of ultrasound images.
The goal of the team’s study was to demonstrate the potential for deep-learning architecture to support early and reliable identification of cystic hygroma from first trimester ultrasound scans. Cystic hygroma is an embryonic condition that causes the lymphatic vascular system to develop abnormally. It’s a rare and potentially life-threatening disorder that leads to fluid swelling around the head and neck.
The birth defect can typically be easily diagnosed prenatally during an ultrasound appointment, but Dr. Walker — co-founder of the OMNI Research Group (Obstetrics, Maternal and Newborn Investigations) at The Ottawa Hospital — and his research group wanted to test how well AI-driven pattern recognition could do the job.
“What we demonstrated was in the field of ultrasound we’re able to use the same tools for image classification and identification with a high sensitivity and specificity,” says Dr. Walker, who believes their approach might be applied to other fetal anomalies generally identified by ultrasonography.
Story Source:
Materials provided by University of Ottawa. Note: Content may be edited for style and length.

Consumption of seven or more units of alcohol per week is associated with higher iron levels in the brain, according to a study of almost 21,000 people publishing July 14 in the open access journal PLOS Medicine. Iron accumulation in the brain has been linked with Alzheimer’s and Parkinson’s diseases and is a potential mechanism for alcohol-related cognitive decline.
There is growing evidence that even moderate alcohol consumption can adversely impact brain health. Anya Topiwala of the University of Oxford, United Kingdom, and colleagues explored relationships between alcohol consumption and brain iron levels. Their 20,965 participants from the UK Biobank reported their own alcohol consumption, and their brains were scanned using magnetic resonance imaging (MRI). Almost 7,000 also had their livers imaged using MRI to assess levels of systemic iron. All individuals completed a series of simple tests to assess cognitive and motor function.
Participants’ mean age was 55 years old and 48.6% were female. Although 2.7% classed themselves as non-drinkers, average intake was around 18 units per week, which translates to about 7½ cans of beer or 6 large glasses of wine. The team found that alcohol consumption above seven units per week was associated with markers of higher iron in the basal ganglia, a group of brain regions associated with control of motor movements, procedural learning, eye movement, cognition, emotion and more. Iron accumulation in some brain regions was associated with worse cognitive function.
This is the largest study to date of moderate alcohol consumption and iron accumulation. Although drinking was self-reported and could be underestimated, this was considered the only feasible method to establish such a large cohort’s intake. A limitation of the work is that MRI-derived measures are indirect representations of brain iron, and could conflate other brain changes observed with alcohol consumption with changes in iron levels.
Given the prevalence of moderate drinking, even small associations can have substantial impact across whole populations, and there could be benefits in interventions to reduce consumption in the general population.
Topiwala adds, “In the largest study to date, we found drinking greater than 7 units of alcohol weekly associated with iron accumulation in the brain. Higher brain iron in turn linked to poorer cognitive performance. Iron accumulation could underlie alcohol-related cognitive decline.”
Story Source:
Materials provided by PLOS. Note: Content may be edited for style and length.