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Childbirth-Related Injuries Decline, Linked With Use Of Instruments, AHRQ Report Finds
There were nearly 158,000 potentially avoidable childbirth-related injuries to women and their infants in 2006, a significant decline from 2000, according to a report by the Agency for Healthcare Research and Quality, HealthLeaders Media reports. The report used data submitted for 15 million discharges by 1,900 hospitals in 25 states, including the largest states -- California, New York, Florida and Texas. Between 2000 and 2006, the rate of potentially avoidable injuries during vaginal childbirth without the use of instruments, such as forceps, declined by 30%, according to the report. The injury rate declined by 21.3% for vaginal childbirth using instruments and by 16.7% for women undergoing caesarean sections. Report author Roxanne Andrews of AHRQ said that the report did not examine factors that might have contributed to the declining injury rates but added that it is an area for further study.The report found that rates of injury were higher when instruments were used during childbirth. For instance, trauma to the woman during vaginal delivery with the use of instruments occurred 160.5 times per 1,000 discharges, compared with 36.2 times when instruments were not used. The report said that the most common injuries to women were perineum tears, which are avoidable in many cases. Traumatic injury to infants during childbirth -- such as broken collarbones, head injuries and infections -- occurred 1.6 times per 1,000 discharges.The report also highlighted care disparities between women in low-income areas and those in high-income areas. Women giving birth in high-income areas had 44% more injuries during vaginal delivery than their counterparts in low-income areas. Black and Hispanic women experienced fewer injuries than white women, while Asian American and Pacific Islander women experienced the highest rate of injuries. The report found that women covered by Medicaid were less likely to be injured during childbirth -- 127 injuries per 1,000 deliveries -- compared with women with private insurance plans -- 185 injuries per 1,000 deliveries. However, the rate of injury for infants covered under Medicaid was higher -- 1.7 per 1,000 deliveries -- than those under private plans -- 1.5 per 1,000 deliveries.The report encouraged providers to evaluate their practices to better understand why such complications occur. According to the report, "Identifying which types of patient safety problems exist for different sub-groups of patients is an important first step in developing interventions to reduce disparities and achieve high quality of care for all patients" (Clark, HealthLeaders Media, 6/18).

More Countries Move Ahead With H1N1 Vaccine Testing
The race to develop a H1N1 (swine flu) vaccine before the fall flu season ramped up Wednesday, after Australia launched the first human trials of the H1N1 vaccine and scientists from the U.S., China and Britain announced plans for human trials of an H1N1 vaccine in coming weeks, AFP/France24.com reports (7/23).
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Toxic Molecule May Help Birds 'See' North And South
Researchers at the University of Illinois report that a toxic molecule known to damage cells and cause disease may also play a pivotal role in bird migration. The molecule, superoxide, is proposed as a key player in the mysterious process that allows birds to "see" Earth"s magnetic field.
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Ewing's Sarcoma: New Direction For Drug Discovery Highlighted By GUMC Discovery

In a discovery that rebuffs conventional scientific thinking, researchers at Georgetown University Medical Center (GUMC) have discovered a novel way to block the activity of the fusion protein responsible for Ewing"s sarcoma, a rare cancer found in children and young adults. In the paper published online July 5 in Nature Medicine, they report discovering and successfully testing a small molecule that keeps the fusion protein from sticking to another protein that is critical for tumor formation. The researchers say this interaction is unique - and is especially surprising since the Ewing"s sarcoma fusion protein is extremely flexible, which allows it to change shape constantly. "Most targeted small molecule cancer drugs inhibit the intrinsic activity of a single protein, but our agent stops two proteins from interacting. This has never been shown before with a cancer-causing fusion protein and represents a potentially novel medical therapy in the future," says the study"s lead investigator, Jeffrey Toretsky, MD, a pediatric oncology physician and researcher at GUMC"s Lombardi Comprehensive Cancer Center. The study could provide a model upon which to design treatment for other disorders caused by the interaction between two proteins, and may be especially useful in cancers caused by translocations of genes, such as sarcomas and leukemias, the researchers say. Agents in use now that work against fusion proteins inhibit a single protein to stop intrinsic enzymatic activity; one example is Gleevec, used for chronic myelogenous leukemia (CML). The Ewing"s sarcoma fusion protein, known as EWS-FLI1, lacks enzymatic activity, "and this difference is why our work is significant," Toretsky says. In the United States, about 500 patients annually are diagnosed with the cancer, and they are treated with a combination of five different chemotherapy drugs. Between 60-70 percent of patients survive over time, but with side effects from the treatment. Few additional treatment options are available for patients whose cancer progresses, Toretsky says. Ewing"s sarcoma is caused by the exchange of DNA between two chromosomes, a process known as a translocation. The new EWS-FLI1 gene is created when the EWS gene on chromosome 22 fuses to the FLI1 gene on chromosome 11, and its product is the fusion protein responsible for cancer formation. It is a so-called disordered protein, which means it does not have a rigid structure. A number of cancer-causing proteins are disordered. In their 15-year search for a new treatment for Ewing"s sarcoma, Toretsky and his colleagues were the first to make a recombinant EWS-FLI1 fusion protein. They used it to discover that the fusion protein stuck to another protein, RNA helicase A (RHA), a molecule that forms protein complexes in order to control gene transcription. "We believe that when RHA binds to EWS-FLI1, the combination becomes more powerful at turning genes on and off," says the study"s first author, Hayriye Verda Erkizan, PhD, a postdoctoral researcher in Toretsky"s lab. Then, from a library of 3,000 small molecules loaned to Georgetown from the National Cancer Institute, the researchers searched for a small molecule that would bind on to EWS-FLI1. They found one, and further discovered the same molecule, NSC635437, could stop EWS-FLI1"s fusion protein from sticking to RHA. This was a wonderful discovery, Erkizan says, because the notion long accepted among scientists is that it is not possible to block protein-protein interactions given that the surface of many of these proteins are slippery - much too flexible for a drug to bind to. They tested the agent in laboratory cell culture, and with the help of GUMC"s Drug Discovery Program, the researchers designed a stronger derivative compound they called YK-4-279. In this study, they tested YK-4-279 in two different animal models of Ewing"s sarcoma and found that the agent significantly inhibited the growth of tumors. There was an 80% reduction in the growth of treated tumors compared to untreated tumors. Toretsky says that while the agent needs to be "optimized," these results serve as a proof of principle that inhibiting protein-protein interaction can work as a novel therapeutic that will target only cancer cells. "We may be able to use this strategy to attack proteins we thought to be impervious to manipulation," he says. The study was funded by grants from the National Institutes of Health, Children"s Cancer Foundation of Baltimore, MD, Go4theGoal Foundation, Dani"s Foundation of Denver, the Liddy Shriver Sarcoma Initiative, the Amschwand Sarcoma Cancer Foundation, the Burroughs-Wellcome Clinical Scientist Award in Translational Research, and the GUMC Drug Discovery Program. Toretsky and co-authors Milton L. Brown, Aykut çœren and Yali Kong are inventors on a patent application that has been filed by Georgetown University related to the technology described in this paper. The other authors report no related financial interests. Karen Mallet Georgetown University Medical Center


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