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Newswise — A team of researchers from nine leading academic hospitals and research centers have published a paper in the early online edition of the journal Cancer that describes pulmonary outcomes among childhood cancer survivors. The study also evaluates the impact of complications such as asthma, chronic cough, emphysema and recurrent pneumonia on daily activities. Led by Andrew C. Dietz, MD, MSCR, of the Center for Childhood Cancer and Blood Diseases at Children’s Hospital Los Angeles, and Daniel A. Mulrooney, MD, of St. Jude Children’s Research Hospital, the study shows that cumulative incidence of lung complications continues to increase up to 25 years from initial cancer diagnosis, and survivors treated with a combination of chemotherapy and radiation are at highest risk. Based on self-reporting by more than 14,000 individuals identified through the Childhood Cancer Survivor Study, a multi-institutional retrospective cohort study, the findings suggest the need for follow-up health care with advancing age and time from diagnosis. Medical advances have led to improved survival rates for children diagnosed with cancer – with five-year survival rates now exceeding 80 percent – and it is estimated that there are more than 420,000 survivors of childhood cancer alive in the United States. Despite these improvements, late mortality rates for cancer survivors exceed those of the general population. Leading causes of death in this population include subsequent cancer, followed by pulmonary and cardiovascular events. Lung tissue is particularly sensitive to cancer treatment and the cumulative incidence for pulmonary symptoms -- such as lung fibrosis, chronic cough and difficult or labored breathing with exercise – increases over time. “While often asymptomatic, damage to the lungs may limit activities of daily living with potential impact on the overall quality of life,” said Dietz. The researchers identified 20,690 five-year cancer survivors, of whom 69 percent completed a baseline survey, and/or one of two follow-up surveys years later. A comparison, or control, group of 4,027 survivor siblings were also surveyed. The rates of chronic cough, oxygen need, lung fibrosis and recurrent pneumonia were elevated among survivors when compared to the control group. Survivors with some of these pulmonary events were also more likely to report limitations on their activities than siblings with the same conditions. “This study adds to our understanding of specific, long-term risks to pulmonary health for survivors of childhood cancer, and will help refine guidelines for appropriate screening, health surveillance and counseling,” said Mulrooney, adding that such knowledge will hopefully contribute to the design and testing of better, targeted interventions to decrease adverse pulmonary events in this population. Additional contributors to the study include Yan Chen, University of Alberta, Edmonton; Yutaka Yasui, PhD, Kirsten K. Ness, PhD, Leslie L. Robison, PhD, and Gregory T. Armstrong, MD, St. Jude Children’s Research Hospital; James S. Hagood, Rady Children’s Hospital, San Diego; Eric J. Chow, MD, Fred Hutchinson Cancer Research Center, Seattle; Marilyn Stovall, PhD, University of Texas, M.D. Anderson Cancer Center; Joseph P. Neglia, MD, University of Minnesota; Kevin C. Oeffinger MD, Memorial Sloan Kettering Cancer Center, New York; and Ann C. Mertens, PhD, Emory University, Children’s Healthcare of Atlanta. The study was supported by the National Cancer Institute (CA55727), a Cancer Center Support grant (CA21765), and the American Lebanese-Syrian Associated Charities.

Newswise — Although strollers and carriers are typically used to safely transport children, injuries do occur while using these products. A study conducted by the Center for Injury Research and Policy of the Research Institute at Nationwide Children’s Hospital found that, over a 21-year period from 1990 through 2010, almost 361,000 children aged 5 years and younger were treated in U.S. hospital emergency departments for stroller- or carrier-related injuries – that’s about two children every hour. The study, published online today in Academic Pediatrics, found that most children were injured when they fell from the stroller (67%) or carrier (63%) or when the stroller (16%) or carrier (29%) tipped over. The head (43% stroller, 62% carrier) and face (31% stroller, 25% carrier) were the most commonly injured parts of the body. While many of the injuries were soft tissue injuries like bumps and bruises (39% for strollers, 48% for carriers), traumatic brain injuries (TBIs)/concussions accounted for one-quarter (25%) of stroller-related injuries and one-third (35%) of carrier-related injuries. In fact, the proportion of stroller-related TBIs/concussions doubled during the study period going from 19% of injuries in 1990 to 42% of injuries in 2010 and the proportion of carrier-related TBI/concussions tripled going from 18% of injuries in 1990 to 53% of injuries in 2010. “While these products are used safely by families every day, when injuries do occur they can be quite serious,” said Kristi Roberts, MS, MPH, study author and research associate in the Center for Injury Research and Policy at Nationwide Children’s. “The majority of injuries we saw were head injuries which is scary considering the fact that traumatic brain injuries and concussions in young children may have long term consequences on cognitive development.” While most of the children were sent home after receiving treatment in the emergency department, 7% of children with a carrier-related injury and 2% with a stroller-related injury were hospitalized. This means that every day in the U.S. a child is hospitalized for a stroller or carrier-related injury. TBIs/concussions accounted for 65% of stroller-related hospitalizations and 79% of carrier-related hospitalizations. “As parents, we place our most precious cargo in strollers and carriers every day,” said Roberts. “By taking a few simple steps like making sure your child is buckled up every time he is in his stroller or carrier and being aware of things that can cause these products to tip over can help prevent many of these injuries.” Safety experts recommend the following to help prevent injuries from strollers and carriers: • Always buckle up. Follow all manufacturer’s instructions for properly securing children in strollers or carriers. Make sure your child is seated and buckled in at all times. • Keep handles clear. Hanging heavy items like purses and bags on the handle of strollers can cause them to tip over. Store these items under the stroller or on your shoulder. If getting a new stroller, look for one with a wide wheel base that will be harder to tip over. • Get a model that fits your child. Strollers and carriers are not one-size fits all. Both strollers and carriers have age and weight limits. Make sure to get one that is the right size for your child and follow all manufacturer’s guidelines for use. • Lock it. Lock stroller wheels when you “park” to prevent it from rolling away unexpectedly. Be careful using a stroller near a curb and in high traffic areas where sidewalks are not available. • Keep it low. Keep carriers low to the ground so the child has a shorter fall if the carrier tips over. • Check for recalls. Both strollers and carriers have had recalls in recent years. Check www.recalls.gov to see if the model you plan to use has been recalled. “While the number of overall injuries from strollers and carriers did go down during the 21 years we looked at in our study, it is still unacceptably high,” said Roberts. “The updates to manufacturer standards and frequent product recalls in recent years have been a good first step but the large number of injuries we are still seeing shows we need to do more.” Data for this study were obtained from the National Electronic Injury Surveillance System (NEISS), which is operated by the U.S. Consumer Product Safety Commission. The NEISS database provides information on consumer product-related and sports- and recreation-related injuries treated in hospital emergency departments across the country. The Center for Injury Research and Policy (CIRP) of The Research Institute at Nationwide Children’s Hospital works globally to reduce injury-related pediatric death and disabilities. With innovative research at its core, CIRP works to continually improve the scientific understanding of the epidemiology, biomechanics, prevention, acute treatment and rehabilitation of injuries. CIRP serves as a pioneer by translating cutting edge injury research into education, policy, and advances in clinical care. For related injury prevention materials or to learn more about CIRP, visit www.injurycenter.org.

Newswise — A diet rich in fruits, vegetables, low-fat dairy and reduced in fats and saturated fats (the DASH diet), designed decades ago to reduce high blood pressure, also appears to significantly lower uric acid, the causative agent of gout. Further, the effect was so strong in some participants that it was nearly comparable to that achieved with drugs specifically prescribed to treat gout, a new study led by Johns Hopkins researchers shows. The findings--derived from a randomized clinical trial--could offer an effective, safe and sustainable dietary approach to lower uric acid and possibly prevent gout flare-ups in those with mild to moderate disease and who can't or don't want to take gout drugs. Dietary excesses, such as consuming a lot of red meat and alcohol, have long been associated with gout, a disease marked by high levels of uric acid in the blood and whose causes remain somewhat of an enigma despite centuries of investigation. The Hopkins researchers noted that while symptoms of gout outbreaks -- severe inflammation and sharp pain in the joints, particularly the base of the big toe -- have been linked to elevated uric acid, it's been unclear exactly what type of diet might lower uric acid and decrease the risk of flare-ups. In an effort to find out, Stephen P. Juraschek, M.D., Ph.D., research and clinical fellow in general internal medicine at the Johns Hopkins University School of Medicine, and his colleagues used data from the DASH (Dietary Approaches to Stop Hypertension) clinical trial, a widely popular and often-cited study whose results were first published in 1997. These results showed that the DASH diet --which emphasizes reduced salt, whole grains, fruits, vegetables, low-fat dairy products and reduced intake of red meats, sweets and saturated fats -- had a marked positive improvement on blood pressure and cholesterol. In the original DASH-sodium trial, 412 participants ate either the DASH diet or a typical American diet for three months. For each month of the study, the participants' diets provided a different level of sodium in a random order, including low (1.2 grams per day or about half a teaspoon), medium (2.3 grams per day or about one teaspoon), and a high level (3.4 grams per day or about 1.5 teaspoons). The high sodium level was comparable to the average daily intake in a typical American diet. At baseline and at the end of each sodium intake period, the researchers conducting the original study also took blood samples, which were analyzed for a variety of blood markers, including uric acid. In this new study, Juraschek and his colleagues examined these data to determine whether and how each intervention affected uric acid blood concentrations. They found that the DASH diet led to a modest 0.35 milligrams per deciliter decrease in uric acid concentrations overall. However, the higher participants' baseline uric acid levels, the more dramatic the decrease. For those with the highest baseline uric acid levels--more than 7 milligrams per deciliter -- for example, the decrease was as high as 1.3 milligrams per deciliter. In the context of what is known about levels of uric acid linked to gout flare-up risk, "That's a large reduction in uric acid," explains Juraschek. Gout-treating medications, such as allopurinol, often reduce patients' blood uric acid concentrations about 2 milligrams per deciliter. "When you get as high as the reduction we believe occurred with the original DASH diet in this study, the effect starts being comparable with gout medications." Juraschek noted that the effect of sodium on uric acid concentrations was small, but significant and quite the opposite of what the researchers expected. Specifically, during the part of the DASH trial in which participants were given the least sodium, their uric acid concentrations were the highest, with slight decreases achieved during the medium and high sodium portions of the trial. Although high sodium levels appear to slightly decrease uric acid concentrations, Juraschek cautions against jumping to the conclusion that to reduce blood uric acid it's a good idea to purposely consume lots of sodium. "More than 70 percent of people with gout have high blood pressure," Juraschek says. "If one was to consume more sodium to improve uric acid, it could worsen blood pressure." The researchers caution that further research is needed to more clearly establish the link between the DASH diet and uric acid in patients with gout and to directly explore whether the DASH diet might reduce or prevent gout flare-ups. But, they conclude, the new study, described in the August 15 issue of Arthritis and Rheumatology, could offer patients a viable way to control uric acid concentrations -- and presumably gout flare-ups -- through a diet already shown to have positive effects on blood pressure, a well-established risk factor for cardiovascular disease. There are about 8.3 million people in the United States with gout, costing the health care system an estimated $7.7 billion. "Results of this trial are good news to patients with high blood levels of uric acid or those at risk for gout. A dietary approach to prevent gout should be considered first line therapy. This study suggests that standard dietary advice for uric acid reduction which is to reduce alcohol and protein intake, should now include advice to adopt the DASH diet," says senior author Edgar R. Miller III, M.D. Ph.D., professor of medicine at the Johns Hopkins University School of Medicine. Other researchers who participated in this study include Allan C. Gelber, M.D., Ph.D., Lawrence J. Appel, M.D., M.P.H., and Edgar R. Miller III, M.D. Ph.D., all from Johns Hopkins, and Hyon K. Choi, M.D., Dr.P.H., of Harvard Medical School. Funding for this study was provided by the National Heart Lung and Blood Institute under grant/contract numbers U01-HL57173, U01-HL57114, U01-HL57190, U01-HL57139, K08 HL03857-01 and U01-HL57156 and by the General Clinical Research Program of the National Center for Research Resources under grant/contract number M01-RR02635 and M01-RR00722. Juraschek receives support from The National Institute of Diabetes and Digestive and Kidney Diseases under grant number T32DK007732-20.

Newswise — Think one little sugary soda won’t make a difference on your waistline? Think again. If people replace just one calorie-laden drink with water, they can reduce body weight and improve overall health, according to a Virginia Tech researcher. “Regardless of how many servings of sugar-sweetened beverages you consume, replacing even just one serving can be of benefit,” said Kiyah J. Duffey, an adjunct faculty member of human nutrition, foods, and exercise in the College of Agriculture and Life Sciences and independent nutrition consultant. Consuming additional calories from sugary beverages like soda, energy drinks, and sweetened coffee can increase risk of weight gain and obesity, as well as Type 2 diabetes and cardiovascular disease. Duffey’s findings, which were recently published in Nutrients, modeled the effect of replacing one 8-ounce sugar-sweetened beverage with an 8-ounce serving of water, based on the daily dietary intake of U.S. adults aged 19 and older, retrieved from the 2007-2012 National Health and Nutrition Examination Surveys. Duffey, along with co-author Jennifer Poti, an assistant professor of nutrition at the University of North Carolina at Chapel Hill, showed that this one-for-one drink swap could reduce daily calories and the prevalence of obesity in populations that consume sugary beverages. The 2015 Dietary Guidelines for Americans recommend that no more than 10 percent of daily calories come from added sugar and that calorie-free drinks, particularly water, should be favored. “We found that among U.S. adults who consume one serving of sugar-sweetened beverages per day, replacing that drink with water lowered the percent of calories coming from drinks from 17 to 11 percent,” Duffey said. “Even those who consumed more sugary drinks per day could still benefit from water replacement, dropping the amount of calories coming from beverages to less than 25 percent of their daily caloric intake.” As Duffey found, a reduction in the amount of daily calories coming from sugary drinks also improves individual scores on the Healthy Beverage Index – a scoring system designed to evaluate individual beverage patterns and their relation to diet and health based on standards set forth by the Beverage Guidance Panel and the Dietary Guidelines for Americans. Duffey developed this index in 2015 with Virginia Tech nutrition researcher Brenda Davy, a professor of human nutrition, foods, and exercise in the College of Agriculture and Life Sciences and a Fralin Life Science Institute affiliate. Their preliminary data showed that higher scores correlate to better cholesterol levels, lowered risk of hypertension, and in men, lowered blood pressure. The broader goal of the index is to help people identify what and how much they drink each day, as drinking habits can impact eating habits. Higher calorie drinks, such as sweetened soda and high-fat milk, have been associated with diets rich in red and processed meats, refined grains, sweets, and starch, according to a 2015 review study by Duffey, Davy, and Valisa Hedrick, an assistant professor of human nutrition, foods, and exercise in the same college at Virginia Tech. Lower-calorie drinks, such as water and unsweetened coffee and tea, were associated with alternative diets rich in fruits, vegetables, whole grains, fish, and poultry. Diet drinks are also healthier alternatives to sugary drinks, explained Duffey, but other research has shown that people who drink water over low-calorie alternatives still tend to eat more fruits and vegetables, have lowered blood sugar, and are better hydrated. The initial study was funded by the Drinking Water Research Foundation, an independent not-for-profit organization that supports research in areas related to consumer- and drinking-water-industry interest. Written by Cassandra Hockman.

Newswise — ANN ARBOR, Mich.– Black adults rate school violence and racial inequities higher on their list of children’s health concerns than other groups, a new national poll says. Among black adults, 61 percent believe racial inequities are “a big problem” for children in the U.S., compared to 17 percent of white adults and 45 percent of Hispanic adults, according to the 2016 annual survey of top children’s health concerns by the C.S. Mott Children’s Hospital National Poll on Children’s Health. Racial inequities and school violence were No. 2 and No. 3 on the list of child health concerns among black Americans. Gun injuries — which did not make any other group’s top 10 list — ranked seventh. The findings come in the wake of a series of high-profile news events regarding racial inequities and safety among black youth. “This year’s survey taps into some key differences across racial and ethnic groups on which issues are viewed as the biggest problems for children in our country,” says poll co-director Gary Freed, M.D., M.P.H., professor of pediatrics at U-M’s C.S. Mott Children’s Hospital and founding director of the Child Health Evaluation and Research (CHEAR) Unit. “One of the most striking differences was seen in how black and white respondents viewed racial inequity: black adults, but not their white counterparts, recognize unequal treatment as a child health concern. In addition, the top 10 rating among black adults for school violence and gun-related injuries mirror national attention regarding the safety of black youth.” Mental health worries for parents and families Mental health was also a dominant concern for black, white and Hispanic parents. Overall, 7 of the Top 10 concerns reflect children’s mental health: either specific mental health problems (depression, stress and suicide) or issues that often have an underlying mental health component (bullying, obesity, drug abuse, school violence). Bullying was the overall #1 child health concern. “We continue to see increasing concern for children’s mental health. There is a great need for children to have access to mental health professionals who can diagnose and treat stress, depression and other mental health conditions as well as prevent suicide,” Freed says. “We know mental health issues can increase children’s risk for obesity, drug abuse and other critical health issues. The broad recognition of mental health as a key child health concern supports the importance of ensuring access to mental health services for all U.S. children.” For the first time in the NPCH survey, suicide made the top 10. With teen suicide now the second-leading cause of death among adolescents, new guidelines from the American Academy of Pediatrics also recently called for teen check-ups to include suicide risk screening. The high concern for mental health issues among youth is consistent with previous Mott poll findings. An April 2016 poll found more than half of adults perceive the mental/emotional health of kids today to be worse than when they were kids. The public pointed to several factors, including higher stress and diminished quality family time. Bullying, obesity and drug abuse remained the top concerns for a third year in a row overall. Other health concerns in the Top 10 included internet safety, child abuse and neglect and sexting. This is the tenth year adults were asked to rate their concerns for kids’ health in the C.S. Mott Children’s Hospital Poll.

Newswise — MINNEAPOLIS – Starting medication for multiple sclerosis (MS) in people who show the beginning signs of the disease is associated with prolonging the time before the disease is definitively diagnosed, according to a long-term study published in the August 10, 2016, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study involved people who had a first episode that was suggestive of MS, such as numbness, vision problems or problems with balance, and an MRI that showed signs of possible MS. Up to 85 percent of people in this situation, which is called clinically isolated syndrome, will in time be diagnosed with MS. “Not much research has been done on how starting treatment this early affects the long-term course of the disease,” said study author Ludwig Kappos, MD, of University Hospital Basel in Basel, Switzerland, and a member of the American Academy of Neurology. “Our study adds to the evidence supporting treatment at the earliest sign of the disease and indicates that early treatment has a long-lasting effect on disease activity.” The study started with 468 people randomly assigned to receive either early treatment with interferon beta-1b or a placebo. After participants were diagnosed with MS or after two years, the participants on the placebo could switch to interferon beta-1b or another drug. After 11 years, researchers reevaluated the 278 people who were still participating in the study, which included 167 people in the early group and 111 people in the delayed group. Those who received the early treatment were 33 percent less likely to be diagnosed with MS than those who received the delayed treatment. People in the early group also had more time before their first relapse of the disease than people in the delayed group, with 1,888 days compared to 931 days. The early group also had a lower overall yearly relapse rate of 0.21 compared to 0.26 for the delayed group, which is 19 percent lower. There was no difference between the two groups in the tests that measure overall disability or in MRI scans measuring the amount of damage caused by the disease. “Overall, early treatment appears to have a benefit on relapses, especially early in the disease, but limited effects on other outcome measures, including outcomes reported by patients,” said Brian C. Healy, PhD, of Brigham and Women’s Hospital and Massachusetts General Hospital in Boston and a member of the American Academy of Neurology, who wrote an accompanying editorial. Limitations of the study include that participants and researchers learned after the fifth-year tests which participants received the drug and which received the placebo and that after the placebo-control phase of the study, all of the participants received treatment, so there was no untreated control group after that point. The study was supported by Bayer HealthCare Pharmaceuticals. To learn more about multiple sclerosis, please visithttp://www.aan.com/patients. The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with 30,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson’s disease and epilepsy.

Newswise — Women with polycystic ovary syndrome (PCOS) who receive frozen embryos during in vitro fertilization have safer and more successful pregnancies than those who get fresh embryos, according to the results of a recent collaboration between Penn State College of Medicine and Chinese researchers. PCOS is a hormonal disorder that affects up to 10 percent of women of childbearing age. When women with PCOS undergo in vitro fertilization, they have an increased risk of a dangerous complication called ovarian hyperstimulation syndrome. This condition can become fatal, and it may require pain medications, intravenous fluids, hospitalization and additional surgical procedures. Women with PCOS also have a greater risk of other pregnancy complications, including pregnancy loss, preeclampsia – high blood pressure during pregnancy, preterm delivery, low birth weight and birth defects. Although fresh embryos have been preferred for in vitro fertilization, previous research has suggested that frozen embryos could improve the rate of live births and lower the rates of ovarian hyperstimulation syndrome and pregnancy complications in women with PCOS. In the new study, which took place at several reproductive medical centers throughout China, 1,508 infertile women with PCOS were randomized to receive either fresh embryos or frozen embryos during their first in vitro fertilization cycle. Results appear today (Aug. 10) in the New England Journal of Medicine. Using frozen embryos lowered the rate of ovarian hyperstimulation syndrome compared to using fresh embryos from 7.1 to 1.3 percent. The group that received frozen embryos also had a higher frequency of live births—due to fewer pregnancy losses—and higher birth weights. "Women with PCOS may have a higher chance of a successful pregnancy and may have less ovarian hyperstimulation when you electively freeze all the embryos and perform a frozen embryo transfer than if you do a fresh transfer," said Dr. Richard Legro, professor of obstetrics and gynecology and public health sciences at Penn State College of Medicine. "This protocol potentially offers immediate benefits to women with PCOS, so practitioners should consider freezing all embryos for these patients." The use of hormones and medications to overstimulate the ovaries to release multiple eggs during in vitro fertilization is thought to create a potentially harmful environment for implantation, especially in women with PCOS, Legro said. Frozen embryo transfer allows a woman's ovary to recover from ovarian stimulation during in vitro fertilization and also gives time for her exposed endometrial lining to shed. "By electing to freeze all the embryos, you create a healthy environment for the best embryos, as opposed to putting them back in a disturbed environment," Legro explained. Frozen embryo transfer was also associated with higher rates of two negative outcomes compared to fresh embryo transfer, the researchers reported. Preeclampsia and neonatal death were more common in the frozen embryo transfer group. However, no patients developed severe preeclampsia pressure during pregnancy and the difference in neonatal death rates was not statistically significant. Both adverse outcomes need to be studied further, according to Legro, who led a team that hosted the Chinese collaborators at Penn State College of Medicine for five weeks as the group wrote the protocol for the multi-center trial and participated in regular steering committee meetings overseeing the trial. Other researchers are Zi-Jiang Chen, Yuhua Shi, Daimin Wei, Jiayin Liu, Junhao Yan, Yingying Qin and Heping Zhang, all of Center for Reproductive Medicine, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China; Yun Sun, Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai, China; Bo Zhang, Center for Reproductive Medicine, Maternal and Child Health Hospital in Guangxi, China; Xiaoyan Liang, Center for Reproductive Medicine, Reproductive Medicine Center, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Yunxia Cao, Center for Reproductive Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, China; Jing Yang, Center for Reproductive Medicine, Wuhan University, China; Jing Li, Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, China; Ning Weng, Reproductive Medicine Center of Jinghua Hospital, Shenyang, China; Lifeng Tian, Center for Reproductive Medicine, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, China; Cuifang Hao, Center for Reproductive Medicine of Yantai Yuhuangding Hospital; Dongzi Yang, Center for Reproductive Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China; Feng Zhou, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine, China; Juanzi Shi, Assisted Reproduction Center, Maternal and Child Health Care Hospital of Shanxi Province, China; Yongle Xu, Center for Reproduction and Genetics, Suzhou Municipal Hospital, Suzhou, China; and Han Zhao, Department of Biostatistics, Yale University School of Public Health. The National Basic Research Program of China, State Key Program of National Natural Science Foundation of China, National Natural Science Foundation of China and Thousand Talents Program funded this research.

Newswise — New Brunswick, N.J. –  Research from investigators at Rutgers Cancer Institute of New Jersey and Princeton University has identified a new approach to cancer therapy in cutting off a cancer cell’s ‘fuel supply’ by targeting a cellular survival mechanism known as autophagy. Rutgers Cancer Institute Deputy Director Eileen P. White, PhD, distinguished professor of molecular biology and biochemistry in the School of Arts and Sciences at Rutgers, The State University of New Jersey, and Rutgers Cancer Institute researcher‘Jessie’ Yanxiang Guo, PhD, assistant professor of medicine at Rutgers Robert Wood Johnson Medical School, are the co-corresponding authors of the work published in the August 10 edition of Genes & Development (doi: 10.1101/gad.283416.116). They share more about the research, which focused on lung cancers driven by the Kras protein: Q: Why is this topic important to explore?A: Between 85 to 90 percent of lung cancers are non-small-cell lung cancer (NSCLC), and response to standard treatment is typically poor. Some subsets of patients with metastatic disease have seen improved survival thanks to recently developed therapies that target particular lung cancer mutations in the EGFR, MAPK, and PI3K signaling pathways. Mutations in the Ras protein family – including Kras – are frequently detected in NSCLC, but drugs directly targeting Ras mutations in NSCLC have not been effective. Understanding the critical cellular process of autophagy and its role in Kras-driven tumor cells may lead to new therapeutic approaches for NSCLC. Q: What is autophagy and how does this process relate to what we already know? A: Cells eat themselves in times of starvation and stress by a process called autophagy. It was long believed that autophagy allows cells to digest and recycle part of themselves to support their metabolism and survive interruptions in their supply of nutrients. But whether this is true, and what the recycling was needed for, was not known. Cancer cells turn on autophagy and use it to survive too, even more so than normal cells. Previously, the White and Guo groups discovered that cancer cells activated by the Ras protein family require autophagy for cell maintenance, metabolic stress tolerance and tumor development. When Ras proteins are ‘switched on,’ they have the ability to turn on other proteins that can activate genes responsible for cell growth and survival. Therefore, understanding what autophagy does can reveal an inherent weakness exploitable for cancer therapy. Q: How did your team approach the work and what did you learn?A: The Guo, Chang and White groups at Rutgers worked together with the Rabinowitz group at Princeton University to find out how autophagy enables cancer cells to survive stress. Using the tumor derived cell lines generated from genetically engineered mouse models for Kras-driven NSCLC, we traced the path of intracellular components cannibalized by autophagy through an analytical laboratory technique known as mass spectroscopy. We found that cancer cells do indeed breakdown and recycle themselves to survive starvation. This cannibalization of cellular parts provides fuel to the powerhouses of the cell, the mitochondria, to maintain their energy levels. Thus, blocking autophagy cuts off the fuel supply to the powerhouses, creating and energy crisis and ultimately cancer cell death. Q: What is the implication of this finding?A: This finding suggests that cutting of ‘fuel’ to cancer cells by blocking autophagy may be a potential therapeutic strategy for Kras-driven lung cancers. Future research should clarify if the autophagy pathways identified in Kras-driven lung cancers can be applied to other forms of cancer. This work was supported in part by National Institutes of Health grants: R01 CA130893, R01 CA188096, R01 CA193970, R01 CA163591, K22 CA190521, P30 CA072720; and the Functional Genomics shared resources of Rutgers Cancer Institute for mitochondrial DNA extraction and DNA sequencing. ###

Newswise — As humans evolved over many thousands of years, our bodies developed a system to help us when we start running and suddenly need more oxygen. Now, using that innate reflex as inspiration, UCLA researchers have developed a noninvasive way to treat potentially harmful breathing problems in babies who were born prematurely. The technique uses a simple device that tricks babies’ brains into thinking they are running, which prompts them to breathe. Each year, about 150,000 babies are born after only 23 to 34 weeks of gestation, which puts them at risk for apnea of prematurity, a condition in which breathing stops, often for several seconds, accompanied by severe falls in oxygenation. The condition occurs because — in infants whose systems not yet fully formed — the respiratory system ignores or cannot use the body’s signals to breathe. Compounding the danger, premature newborns’ lungs are not fully developed, and therefore do not have much oxygen in reserve. When breathing stops in these periods of apnea, the level of oxygen in the body goes down, and the heart rate can drop. That combination can damage the lungs and eyes, injure the nerves to the heart, affect the hormonal system (which can lead to diabetes later in life), or injure the brain (which can result in behavioral problems later in life). Hospitals use a range of approaches to minimize the duration of premature babies’ breathing pauses — placing them on their stomach, forcing air into the lungs with a facemask and giving caffeine to stimulate the brain — but none is perfect and each carries other risks. According to Dr. Ronald Harper, a distinguished professor of neurobiology at the David Geffen School of Medicine at UCLA, even newborns have the innate mechanism that triggers increased breathing. “When our feet hit the ground running, we flex muscles and joints that have nerve fibers leading to the brain which signal that the body is running,” he said. “This message is coupled with another set of fibers to parts of the brain that regulate breathing and sends a signal that those parts need to increase breathing. Fortunately, that coupling exists even in extremely young infants.” The idea to use an external breathing device to treat apnea of prematurity arose over a cup of coffee between Harper and Dr. Kalpashri Kesavan, a neonatologist at Mattel Children’s Hospital UCLA, when the conversation turned to how a baby’s breathing could be supported if the brain was told the baby was running or walking. Harper’s lab, which focuses on brain mechanisms that drive breathing during sleep, had already developed a device that he had intended to test for treating people with breathing problems. The device is a pager-sized box with wires that connect to small disks which are placed on the skin over the joints of the feet and hands. (Placing them on the hands is another nod to how the human body evolved: Early humans ran on all fours, so nerves in the hands are still involved in signaling the brain that the body is running.) Once the battery-powered machine is turned on, the disks gently vibrate, which triggers nerve fibers to alert the brain that the limb is moving. “We thought that if this reflex were going to work for any kind of sleep disorder with breathing problems, then premature infants would be the No. 1 target, because breathing stoppages are so common and have the potential to do so much injury,” Kesavan said. “It’s almost like it was naturally made for them.” The researchers tested the device on 15 premature infants who were born after 23 to 34 weeks of gestation, and who were experiencing breathing pauses and low oxygen. The disks were placed on one hand and one foot, and the device was turned on for six hours at a time, followed by six hours off, for a total of 24 hours. The scientists compared the babies’ vital signs during the periods when the device was on with the times when it was off. They found that when it was on, the number of incidents when babies’ oxygen levels were low was reduced by 33 percent and the number of breathing pauses was 40 percent lower than when it was off. The device also reduced low–heart-rate episodes by 65 percent, which is especially significant because slow heart rate can impair the flow of blood to vital tissues. The findings were published online in the Journal PLOS One. The researchers now plan to study the approach on a larger number of patients and over a longer period of time. They’ll also study the effects of the device on blood pressure and other cardio-respiratory measures, as well as its impact on sleep quality. Breathing stoppages typically wake infants, and reducing the number of pauses in their breathing should lead to less disturbed sleep. While most premature babies eventually grow out of their breathing problems, it can take weeks to months before their respiratory systems develop sufficiently to allow them to breathe on their own at all times. “Long-term use of the device could decrease breathing pauses, maintain normal oxygen levels, stabilize the cardiovascular system and help improve neurodevelopmental outcomes in preterm infants,” Kesavan said. “We may be able to bring about this change with something that is noninvasive, drug-free and has no side effects, and there is nothing better than that.” Harper is also testing the device on adolescents who suffer breathing problems due to spinal cord injuries and adults with sleep-disordered breathing, including obstructive sleep apnea. The University of California has applied for a patent for the device, and is discussing its commercialization with several companies. The study’s other authors are Paul Frank, Daniella Cordero and Dr. Peyman Benharash, all of UCLA, and the research was supported by grants from the UCLA Children’s Discovery and Innovation Institute. Justin Stephens/Mattel Children's Hospital UCLA A Simple Treatment for Common Breathing Problem of Premature Infants | UCLA Health Newsroom

Newswise — MADISON, Wis. — Imbed Biosciences today received clearance from the Food and Drug Administration to market its patented wound dressing for human use. The dressing it calls Microlyte Ag is a sheet as thin as Saran Wrap and can conform to the bumps and crevices of a wound, says company CEO Ankit Agarwal. The dressing is now cleared by the FDA as a class II medical device, for prescription and over-the-counter use. Like many dressings now used to treat burns and other persistent wounds, Microlyte Ag contains silver to kill bacteria – but in much smaller quantities."Silver is an excellent antimicrobial agent," says Agarwal, a co-founder of the company in the Madison suburb of Fitchburg, "as it is active against a broad range of bacteria and yeast. But the large silver loads found in conventional silver dressings can be toxic to skin cells. Our dressing uses as little as 1 percent as much silver as the competition, and yet the tests we submitted to the FDA showed that Microlyte kills more than 99.99 percent of bacteria that it contacts." That kill ratio even appeared in tests against some of the nastiest hospital-acquired superbugs, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus. Microlyte overcomes a key problem with existing dressings: stiffness. Under a low-power microscope, a wound has bumps and fissures — hiding places for bacteria. The Microlyte dressing inherently adheres to moist surfaces and is so flexible that it drops into the fissures, leading to the sweet combination of greater destruction of bacteria at much lower doses of silver.Microlyte has several other advantages, Agarwal says. It retains moisture yet is ultrathin and breathable, allowing oxygen to reach the wound and gases to exit, all factors that promote healing. The slow release of the silver means the dressing can remain in place for at least one day. And because the material is a hydrogel (a water-based gel), it can simply be rinsed off as needed before replacement. Experience with animals shows that the ultra-thin dressing simply sloughs off as the wound heals. All of these advantages should reduce the need to change dressings, which can be so painful that sedation is needed, especially for children. “Reducing or eliminating dressing changes reduces the pain that the patient experiences,” says co-founder Michael Schurr, chair of general surgery at the Mountain Area Health Education Center in Asheville, North Carolina, and adjunct professor of surgery at the University of North Carolina. “It also reduces costs in supplies and reduces the burden to the health care system that supplies visiting nurses to do the dressing changes.” "We are seeing in a limited number of cases that it does provide us with a remarkable new tool for dealing with chronic wounds" in dogs and cats treated at the UW-Madison School of Veterinary Medicine, says Jonathan McAnulty, chair of the Department of Surgical Sciences. "We certainly have no reason to think that this will be different with humans,” adds McAnulty, who is also a company co-founder. “The principles are the same, and a lot of the problems are the same." The dramatic closure of wounds that have resisted months of conventional treatment "suggests that chronic bacterial contamination of the wound surface, even when it looks relatively healthy, is a significant factor inhibiting healing in many cases," McAnulty says. "Once we treat with our dressing, we start to see very dramatic closure of these wounds." McAnulty says he’s starting to use Microlyte earlier in treatment. "Certainly it seems appropriate for prevention of infection as well as treatment."The ultra-thin dressing material was invented in the lab of Nicholas Abbott, a UW–Madison professor of chemical and biological engineering, when Agarwal was a postdoctoral fellow and where he is now an honorary associate scientist. The dressing will compete in the $2 billion market sector of "advanced wound dressings," which are used to treat diabetic ulcers, venous ulcers, burns, bedsores and other difficult wounds. Imbed has 10 employees. The company is developing other ideas for wound treatment and discussing commercial-scale production of Microlyte. Currently, it plans to reach the market through licensing agreements with hospital suppliers. # # #