University of Virginia Foundation

Low-Cost Antibiotic Could Prevent Sepsis in up to 2 Million Women Per Year Research Presented at the Society for Maternal-Fetal Medicine's 43rd Annual Pregnancy Meeting Study Made Possible through Partnership between the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NICHD Global Network for Women's and Children's Health Research, the Bill & Melinda Gates Foundation and the Foundation for the National Institutes of Health NORTH BETHESDA, Md., Feb. 9, 2023 /PRNewswire/ -- The Foundation for the National Institutes of Health (FNIH) today announced that The New England Journal of Medicine (NEJM) has published the results of a study of antibiotic treatment to protect maternal health in resource-limited settings that could benefit up to 2 million women per year.1 The study, called the Azithromycin Prophylaxis in Labor Use Study (A-PLUS), found that one dose of azithromycin, a low-cost, generic, oral antibiotic, given during labor to women planning to deliver vaginally in low- and middle-income countries, can prevent life-threatening sepsis. "The A-PLUS study has remarkable potential to protect maternal health and represents a significant advancement, especially for women who cannot access modern obstetrical care," said Dr. Julie Gerberding, CEO of the Foundation for the National Institutes of Health (FNIH). "This multinational study is an exemplar of what can be accomplished through team science — connecting academic researchers around the world with NIH experts and private foundations, like the Bill & Melinda Gates Foundation, to advance global health breakthroughs. We thank the thousands of women and their care providers in seven countries who agreed to participate in the study even in the midst of a pandemic." Sepsis is a life-threatening condition caused by the body's extreme response to infection and can lead to organ failure and death. The World Health Organization (WHO) estimates sepsis due to obstetric infection is the third most common cause of maternal mortality globally.2 This randomized, placebo-controlled study found that a single dose of azithromycin reduces the occurrence of maternal sepsis by approximately 35%. When a combination of sepsis and death was analyzed, there was a 33% reduction. Given the nearly 6 million cases of maternal sepsis per year,3 the A-PLUS study results suggest that up to 2 million cases of maternal sepsis per year could be prevented with this readily available, affordable medicine. The study was designed to include 34,000 women in seven low- and middle-income countries who received a single dose of azithromycin or placebo during childbirth. However, an interim analysis found the treatment had a significant beneficial effect, and enrollment was halted early for maternal effectiveness after approximately 29,000 women were studied. "Sepsis is one of the leading causes of maternal death worldwide and there is urgent need for low-cost, effective interventions," said Prof. Dr. Antoinette Tshefu Kitoto, Professor of Public Health at Kinshasa School of Public Health and International Principal Investigator of the UNC-Democratic Republic of the Congo site. "We saw such a significant reduction in the incidence of sepsis with azithromycin that we stopped enrolling new participants early to ensure that as many women as possible could benefit from our findings as soon as possible." In addition to a reduction in sepsis, the study found a lower risk of maternal endometritis (uterine infection), hospital readmission and unscheduled medical visits among women who received azithromycin. Azithromycin is an inexpensive, generic antibiotic available in tablet form and suitable for room-temperature storage. The study included women at study sites located in Bangladesh, the Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, and Zambia. Consequently, the results are likely to be useful for informing national health policy and obstetrical practice in similar settings around the world. Investigators also examined the use of azithromycin to prevent sepsis or death in newborns. The intervention had no effect in this population. The drug also had no adverse newborn effects. In addition to publication in The New England Journal of Medicine, the study results were presented simultaneously at the Society for Maternal-Fetal Medicine's 43rd Annual Pregnancy Meeting in San Francisco, Calif. As a result of the study's positive findings, A-PLUS investigators will provide the World Health Organization (WHO) and other professional organizations with the results to inform their guidelines. This groundbreaking multi-site study was conducted by NICHD's Global Network for Women's and Children's Health Research and was co-funded by NICHD and the FNIH, with support to the FNIH provided by a grant from the Bill & Melinda Gates Foundation. Funding partners: Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health Bill & Melinda Gates Foundation Implementing partners: RTI International Boston University in conjunction with Lata Medical Research Foundation (Nagpur, India) Columbia University in conjunction with Aga Khan University (Pakistan) Indiana University School of Medicine in conjunction with Moi University (Kenya) Thomas Jefferson University in conjunction with Jawaharlal Nehru Medical College (Belagavi, India) University of Alabama at Birmingham in conjunction with University of Zambia (Zambia) University of Colorado, Denver in conjunction with the Institute of Nutrition of Central America and Panama (Guatemala) University of North Carolina at Chapel Hill in conjunction with the Kinshasa School of Public Health (Democratic Republic of Congo) University of Virginia in conjunction with the International Center for Diarrheal Disease Research (Bangladesh) Additional information and a short video about the A-PLUS study are available on the FNIH website. About the A-PLUS Study: The Azithromycin Prophylaxis in Labor Use Study (A-PLUS) analyzed the safety and effectiveness of a single intrapartum oral dose of azithromycin compared to placebo, in reducing the risk of neonatal and maternal sepsis or death in laboring women. Single-dose azithromycin is a low-cost, accessible intervention, which was found to improve maternal health. The study was led by Drs. Alan T. N. Tita and Waldemar A. Carlo, from the University of Alabama at Birmingham, and Dr. Elizabeth M. McClure, of RTI International. It was conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Global Network for Women's and Children's Health Research. The study was funded by NICHD and through a grant from the Bill & Melinda Gates Foundation to the FNIH. About the Foundation for the National Institutes of Health: The Foundation for the National Institutes of Health (FNIH) connects the world's leading public and private organizations to accelerate biomedical breakthroughs for patients, regardless of who they are, where they live or what disease they have. Together with leading scientists and problem-solvers, and a successful track record of navigating complex problems, the FNIH accelerates new therapies, diagnostics, and potential cures; advances global health and equity in care; and celebrates and trains the next generation of scientists. Established by Congress in 1990 to support the mission of the NIH, the FNIH is a not-for-profit 501(c)(3) charitable organization. For more information about the FNIH, please visit fnih.org. Follow us on social media: LinkedIn, Twitter, Facebook Contact: Melanie Doupé Gaiser Ruder Finn, on behalf of FNIH 212.593.6459 [email protected] References: Tita A, Carlo W, McClure E, et al. Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth. N Engl J Med. 2023;388:xxx-xxx. Maternal infections in Health Facilities. World Health Organization. . Published April 27, 2020. Accessed January 11, 2023. Rudd KE, Johnson SC, Agesa KM, et al. Global, Regional, and National Sepsis Incidence and Mortality, 1990-2017: Analysis for the Global Burden of Disease Study. The Lancet. 2020; 395(10219):200-211. SOURCE Foundation for the National Institutes of Health

Coronary artery disease is the most common form of heart disease, affecting more than 20 million Americans. It's estimated to be responsible for 1 in 4 deaths in the United States each year. The new gene discovery opens the door to better treatments. University of Virginia researchers and their collaborators have identified genes that play key roles in the development of coronary artery disease, the No. 1 cause of death worldwide. UVA's findings essentially pick culprits responsible for coronary artery disease (CAD) out of a far, far larger lineup of potential genetic suspects. That gives scientists promising targets as they work to develop new and better treatments. "Genetic studies done in more than 1 million people in the last 15 years identified hundreds of locations on our chromosomes that increase the risk of having a heart attack," said senior researcher Mete Civelek, PhD, of UVA's Center for Public Health Genomics and the Department of Biomedical Engineering, a joint program of the School of Medicine and School of Engineering. "We now identified the genes that are responsible for this risk at these locations. We will be able to use these findings as new therapeutic targets." About Coronary Artery Disease Coronary artery disease is the most common form of heart disease, affecting more than 20 million Americans. It's estimated to be responsible for 1 in 4 deaths in the United States each year. The disease is caused by the buildup of fatty plaques in the walls of the arteries that supply blood to the heart, but the genetic (inherited) factors that contribute to its development remain murky. To home in on genes important in the development of CAD, Civelek and his team examined cells collected from 151 previously healthy heart transplant donors from a variety of racial and ethnic backgrounds. This provided the scientists with a tremendous amount of information on gene activity in smooth muscle cells. These cells naturally line our arteries, but they also can serve as the foundation for the fatty plaques that build up inside those arteries. Using the gene-activity data, the scientists worked backward to triangulate specific gene variations responsible for harmful changes in the smooth muscle cells. Understanding these changes sheds light on plaque formation, a process called atherosclerosis, and, ultimately, on the molecular mechanisms responsible for coronary artery disease. "Current drugs that doctors prescribe work to reduce risk factors for heart disease, such as cholesterol-lowering drugs," Civelek said. "However, we need to identify drugs that target the disease where it develops. That is why it is important to find the genes responsible for the disease development in the arteries because that is where the plaques form." The new research provides many important insights into coronary artery disease. For example, the researchers found notable differences in gene activity between males and females in smooth muscle cells. They also identified important differences in smooth muscle cells that were multiplying, or "proliferating," and those that were not. To help his fellow scientists capitalize on the discoveries, Civelek has created a free, user-friendly website that lets heart researchers review and analyze his team's important new data.  "We expect that our findings will provide a rich catalog of genes for the cardiovascular community to study in years to come," Civelek said. "And, of course, we hope some of these genes will be targets of a new class of drugs that target the plaque development in the arteries to the benefit of millions of patients."

A new hybrid catalyst converts carbon dioxide into ethylene in one pot. A new hybrid catalyst converts carbon dioxide into ethylene in one pot. The catalyst was developed by scientists from Ames National Laboratory, Iowa State University, University of Virginia, and Columbia University. This catalyst supports the world net-zero carbon initiative by using carbon dioxide (CO2) as a feedstock for efficient ethylene production powered by electricity. Ethylene is a commodity chemical used to manufacture a wide range of products from plastics to antifreeze. The large-scale production of ethylene is energy intensive and relies heavily on fossil resources. Electrocatalytic production of ethylene from CO2 is emerging as a promising method. This new catalyst consists of only earth-abundant materials, such as nickel and copper, and requires less energy for chemical reaction. Long Qi, a scientist at Ames Lab, explained how the catalyst works. Atomically dispersed nickel anchored on nitrogen assembly carbon (NAC) works to catalyze CO2 to CO at low voltage and high current. The catalyst is effective over a wide range of voltages and its effectiveness at higher currents means a higher rate of CO production. "Since this catalyst remains active over a very wide voltage range, that allows easy coupling with a second catalyst," Qi said. "So we use the second catalyst, which is a copper nanowire, and by combining these two we have a very selective process that has up to 60% efficiency going from CO2 to ethylene in one pot." Another important aspect of the catalyst is its structure. Wenyu Huang, an Ames Lab scientist and Iowa State University professor from the team, noted that the catalyst's porous structure enhances its effectiveness. "Our catalyst has an ordered mesoporous structure that is beneficiary for mass transfer," he said. "Because it's highly porous, you have a very high surface area to expose a lot of nickel's active sites, making our catalyst very effective in CO2 reduction to CO." For Huang, the most exciting aspect of this research was how the team combined the two catalysts to streamline the process. "We basically combine the two best catalysts on their own, and they work together so we can connect the CO2 to CO and the CO to ethylene reactions in one system," he said. Qi emphasized the importance of using CO2 as a feedstock for this reaction, because it addresses the global need to reduce the amount of CO2 released into the atmosphere. He explained that this process can use CO2 recovered from chemical or industrial processes, or from air capture. "And we can do this without any precious metal, simply the nickel, copper, carbon, and nitrogen, to permit large-scale industrial applications," Qi said. "Also, we potentially eliminate the use of fossil resources to make ethylene."