Nisannne Ghonem, assistant professor at the University of Rhode Island’s College of Pharmacy, is a recipient of the 2017 Mentored Research Awards from Advance-CTR, a federally funded statewide effort to support clinical research that can be translated into approaches and policies to improve the health of Rhode Islanders. She is one of three researchers across the state to receive a two-year grant through the awards program, which aims to recruit and train early career health scientists representing diversity in background and discipline. Her research seeks to address a universal problem in kidney transplant surgery that can result in failure of the organ graft. The Advance-CTR (Clinical Translational Research) award covers 75 percent of the researcher’s salary, with additional funds for supplemental tuition or research needs as well as mentoring. “We are tremendously proud of our Mentored Research Awardees, who were selected from an extremely competitive batch of applications. Professor Ghonem shows highly promising research in the area of pharmacology and toxicology, and we look forward to supporting her career development through this award,” said Dr. Ira Wilson, director of the Professional Development Core of Advance-CTR based at Brown University, which runs the Mentored Research Awards program. Ghonem’s research will explore the use of a class of drugs known as prostacyclins to reduce ischemia-reperfusion injury to a transplanted kidney from a deceased patient that can result in failure of the organ graft. These injuries occur when blood flow to the donor organ is unavoidably interrupted (ischemia) and then resumes (reperfusion) upon transplantation. “This injury is inherent in the nature of the transplant surgery, and the problem remains unsolved,” Ghonem said. Prostacyclins, which act as anti-coagulants and vasodilators to improve blood flow, have shown promise in liver transplantation research, she said. Solving the ischemia-reperfusion problem could mean the difference between life and death for the 2 million people worldwide — and 650,000 in the United States — living with end-stage kidney disease and who are in need of organ transplants. “There is a great disparity in the number of patients waiting for transplants and organs available,” Ghonem said. “The discovery of a drug to treat this injury would allow acceptance of more kidney grafts, which could dramatically increase the number of organs available for transplant and improve patient outcomes and survival.” Ghonem’s mentor on the project is Fatemeh Akhlaghi, a URI pharmacy professor and the Ernest Mario Distinguished Chair in Pharmaceutics. The team also comprises two co-investigators and mentors: Dr. Reginald Gohh, associate professor at Brown University’s Alpert Medical School and surgeon and medical director of organ transplantation at Rhode Island Hospital; and Dr. Rujun Gong, associate professor and director of kidney research at the medical school. The researchers will assess the effects of prostacyclin on ischemia-reperfusion in laboratory rats. Such research is the foundation for supporting clinical trials involving adult patients undergoing kidney transplantation, Ghonem’s ultimate aim. Her research targets sub-optimal and extended criteria organ donors, which come from the deceased donor pool that makes up the majority of transplants. So far this year, Rhode Island Hospital — the only facility in the state that performs organ transplants — has conducted 35 kidney transplants, and only seven came from live donors, according to the United Network for Organ Sharing. Circumstances of death, storage/transportation time and other factors affecting how long the kidney is deprived of blood flow increase the chance and extent of injury, and ultimately, the outcome for the patient, Ghonem said. Advance-CTR (Award #U54GM115677) is a statewide program funded by the National Institute of General Medical Science/National Institutes of Health to support clinical and translational researchers in Rhode Island through funding, research resources and services, and professional development. It seeks to support research across the translational science spectrum, including basic science, clinical and public health.
Stony Brook Medicine kidney transplant specialist Frank Darras, MD, Clinical Porofessor of Uroogy and Medical Director of Transplantation Services, is avaiable to discuss kidney transplanation and Lupus patients. Accordng to Dr. Darras, Systemic lupus erythematosus (SLE) is an "autoimmune" disease that can harm your kidneys and other tissues, and may be fatal. SLE that affects the kidneys is called lupus nephritis. If the kidneys fail, lupus patients can be treated with dialysis or a kidney transplant. Many patients with lupus nephritis have received a kidney transplant. The drugs used to prevent rejection of the new kidney are the same or similar to those used to treat lupus. It is unusual for lupus to come back in the new kidney. Lupus patients with new kidneys do as well as any other patients with transplanted kidneys. More than 116,000 people are listed for an organ transplant nationwide. Many face a lengthy wait for an available organ. Yet only approximately 19,000 kidney transplants were performed in the U.S. in 2016, with about 5,600 kidney transplants by living donors. Living kidney donation is an important option for patients with end-stage renal disease (ESRD), and has improved life expectancy and quality for patients otherwise requiring maintenance dialysis. Studies have shown the outcome of a transplant from a living donor is better than that of a deceased donor. With a kidney from a living donor, there’s less waiting for a kidney than one from a deceased donor. A kidney from a living donor usually functions immediately, and for a longer period of time than a kidney from a deceased donor. Many living kidney donor transplants are done between family members. However, spouses, friends and even “strangers” can give the gift of life. While donating a kidney involves major surgery, it is usually performed Laparoscopically thru small incisions with less pain, less scarring and faster recovery to full activity than traditional open surgery. The risk of kidney failure is the same as for people who are not kidney donors, and living kidney donors tend to live longer than those who are not donors, because they have been screened so thoroughly. Donating a kidney is a major decision, but the gift of life is a noble act. The results are great, the downside is minimal. The need for kidney donors, both living and deceased, has never been greater than it is now. As transplantation continues to offer patients better outcomes, more patients are waiting for a kidney that matches their needs. Without an increase in donors, many more people will die before they have an opportunity to receive a life-saving transplant. If you are intent on becoming an organ donor, start by registering at the DMV. Have a discussion with your family and loved ones, so that they will know your wishes and can advocate for you when the time comes. If needed, Dr. Darras and all Stony Brook experts have access to a ReadyCam television studio system that provides remote access to television networks.
Highlights In individuals with chronic kidney disease, high sleep fragmentation was associated with an elevated risk of developing kidney failure. Higher sleep fragmentation and shorter sleep duration were each linked with steeper declines in kidney function over time. Subjectively measured daytime sleepiness was associated with an increased risk of early death from any cause. Sleep disturbances are common in individuals with kidney disease. Newswise — Washington, DC (September 14, 2017) — A new study reveals a potential link between disordered sleep and kidney function loss and early death among individuals with chronic kidney disease (CKD). The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), suggest that people with CKD may be especially vulnerable to the deleterious effects of impaired sleep. Increasing evidence suggests that sleep disorders are common in patients with CKD, but the influence of sleep duration and quality on their health is unknown. To investigate, Ana Ricardo, MD, MPH (University of Illinois at Chicago), Kristen Knutson, PhD (Northwestern University), and their colleagues evaluated sleep (using a wrist-worn accelerometer for 5-7 days) and clinical outcomes including worsening of kidney function over time and death from any cause in 431 individuals with mild-to-moderate CKD. Patients were assessed yearly for a median follow-up of 5 years. During follow-up, 70 patients developed kidney failure and 48 died. High sleep fragmentation was associated with an elevated risk of developing kidney failure. In addition, higher sleep fragmentation and shorter sleep duration were each linked with steeper declines in kidney function over time. Furthermore, subjectively measured daytime sleepiness was associated with an 11% increased risk of death from any cause. “These findings suggest that impaired sleep is an unrecognized and clinically significant risk factor for progression of CKD,” said Dr. Ricardo. “Future work is needed to evaluate interventions to improve sleep habits in patients with CKD and assess whether the observed relationship with CKD progression is causal.” Study co-authors include Jinsong Chen, PhD, Lawrence Appel, MD, Lydia Bazzano, MD, Eunice Carmona-Powell, Janet Cohan, MS, Manjula Kurella Tamura, MD, Susan Steigerwalt, MD, John Daryl Thornton, MD, Matthew Weir, MD, Nicolas Turek, BA, Mahboob Rahman, MD, Eve Van Cauter, PhD, and James Lash, MD. Disclosures: The authors reported no financial disclosures. The article, entitled “The Association of Sleep Duration and Quality with CKD Progression,” will appear online at http://jasn.asnjournals.org/ on September 14, 2017, doi: 10.1681/ASN.2016121288. The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies. Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has nearly 17,000 members representing 112 countries. For more information, please visit www.asn-online.org or contact the society at 202-640-4660.
The incidence of heart disease is on the rise, and new therapeutic strategies are needed. Approaches based on stem cells, which can potentially preserve or even regenerate heart muscle cells damaged by ischemia – a hallmark of heart disease – are especially promising. Now, thanks to an $11.6-Million Program Project Grant (PPG) from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) under award number P01HL134608, scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) are poised to explore new possibilities in stem cell-based treatments for heart repair and regeneration. The project is aimed specifically at better understanding the regenerative capabilities of stem cell-derived microvesicles known as exosomes. The Principal Investigator on the new award is Raj Kishore, PhD, Professor of Pharmacology and Medicine and Director of the Stem Cell Therapy Program in the Center for Translational Medicine at LKSOM. According to Dr. Kishore, exosomes offer an exciting opportunity to develop a cell-free approach to stem cell-based therapy for heart disease. “Previous attempts at stem cell therapy for heart disease did not work as hoped,” Dr. Kishore said. “In many cases, the stem cells themselves were injured by inflammation in the heart following injection or were not functioning optimally, having been weakened from disease, such as diabetes, or age.” Exosomes differ from stem cells in that they are not actually cells. Rather, they are tiny packages, roughly 50-150 nanometers in diameter, which are secreted by stem cells and taken up by neighboring tissue cells. They carry stem cell-specific small RNAs, proteins, and other cargo that mimic stem cell functions once released inside cells, giving them beneficial properties. “In heart cells, the cargo inside exosomes can carry out stem cell activities necessary for cardiac repair,” Dr. Kishore explained. Many questions remain, however, about the function of stem cell-derived exosomes in the heart. It is unknown, for example, whether factors such as a patient's age or disease characteristics modify the ability of exosomes to repair or regenerate heart tissue. To answer those questions, Dr. Kishore and colleagues Walter Koch, PhD, the William Wikoff Smith Chair in Cardiovascular Medicine, Professor and Chair of the Department of Pharmacology, and Director of the Center for Translational Medicine at LKSOM, and Steven R. Houser, PhD, Senior Associate Dean for Research, Vera Goodfriend Professor of Cardiovascular Medicine, Chair of the Department of Physiology, and Director of the Cardiovascular Research Center at LKSOM, devised three collaborative projects. Each of the researchers leads a specific project as part of the new grant. In Dr. Kishore's laboratory, work is focused on understanding the function and content of exosomes from bone marrow stem cells in healthy versus diabetic animals and animals with severe inflammation. “We want to know whether diabetes, which is common in heart disease patients, and inflammation from heart damage change exosome function or affect their cargo, and if so, what changes occur,” he said. “Identifying specific disease-related alterations in exosome molecules will allow us to target and modify the molecules in ways that are beneficial therapeutically for the heart.” Dr. Koch's team is examining signaling pathways in cardiac stem cells involving G-coupled receptor kinase-2 (GRK2). GRK2 inhibition potentially facilitates heart repair through mechanisms that involve alterations to the cargo of secreted exosomes. The third project explores exosomes from cortical bone stem cells, originally discovered in Dr. Houser's laboratory, and their role in heart repair. “This research gives us the opportunity to explore the idea that cell-based exosomes can be used to enhance repair of the heart after a heart attack,” Dr. Houser explained. “Exosomes from cortical bone stem cells may contain factors that could reduce cardiac injury and enhance regeneration.” The new award also funds two scientific cores supporting all 3 projects – an exosome isolation and characterization core directed by Dr. Kishore, and an animal surgery and physiology core led by John Elrod, PhD, Assistant Professor of Pharmacology at the Center for Translational Medicine at LKSOM. “This NIH Award is a testament to what we have built here at Temple,” Dr. Koch said. “Dr. Kishore has shown great leadership in organizing this multi-component grant.” The outcomes of the various projects are expected to have important impacts on the basic scientific understanding of exosomes in the heart and on clinical aspects of heart disease. “The goal will be to translate our findings into novel therapies for patients with heart disease,” Dr. Houser added. Editor’s Note: The content above is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
FINDINGS In a two-year UCLA-led study, nearly two-thirds of people with advanced melanoma responded positively to a treatment that combines the immunotherapy drug pembrolizumab with a herpes virus called talimogene laherpareovec, or T-VEC. Researchers led by Dr. Antoni Ribas found that the treatment's side effects were manageable, and comparable to side effects for people who took either pembrolizumab or T-VEC as a standalone treatment. BACKGROUND UCLA scientists are testing the combination of pembrolizumab (marketed as Keytruda) and T-VEC (marketed as Imlygic) as a treatment option for people with advanced melanoma that doesn't fully respond to either treatment separately. T-VEC is a genetically modified version of the herpes simplex virus that causes cold sores, but is safe to use. T-VEC has already been approved for the treatment of melanoma and it works both by directly killing cancer cells and using a protein that attracts immune cells into the cancers. Pembrolizumab has become a standard-of-care treatment for advanced melanoma, and it is also being used to treat non-small-cell-lung cancer, cancers of the head, neck, kidney and bladder, and Hodgkin's disease. It works by taking the "brakes" off of the body's immune system, enabling it to attack cancer. According to Ribas, people whose melanoma does not respond to pembrolizumab often lack a type of T cell called CD8+ in their tumors; the lack of CD8+ cells seems to prevent immunotherapy drugs from working. But the researchers believe those people might benefit from a combination therapy, because T-VEC attracts CD8+ immune cells to the tumors and pembrolizumab allows them to attack the cancer cells. METHOD The phase 1 clinical trial evaluated 21 people with advanced melanoma. Researchers injected patients' melanoma tumors with T-VEC for six weeks and then gave them infusions of pembrolizumab. Sixty-two percent of the patients had a partial or complete response, meaning that their tumors either shrank or were no longer detectable. IMPACT The combination therapy could provide an alternative treatment for people with melanoma whose tumors don't respond to other therapies. It also being tested in people with head, neck and colon cancers. AUTHORS Ribas, the study's lead author, is director of the immunology program at UCLA's Jonsson Comprehensive Cancer Center, professor of hematology and oncology at the David Geffen School of Medicine at UCLA, and a member of the Parker Institute for Cancer Immunotherapy. JOURNAL The study is published online in the Cell. It is the first full report clinical trial to be published in the journal. FUNDING Funding was provided by Amgen and Merck. DISCLOSURES Ribas has received consulting fees from Amgen and Merck. VIDEO ABSTRACT A video abstract of the study is available for media use. YouTube link: https://youtu.be/pm46mQ7SeXU. For a broadcast-quality version, please contact Peter Bracke at PBracke@mednet.ucla.edu.
The most complete assessment yet of chronic disease in adult survivors of childhood cancer found they have a nearly two-fold greater cumulative burden of chronic health problems than the general public. The St. Jude Children’s Research Hospital study appears today in The Lancet and offers insights for improving health care delivery. Researchers used a statistical method called cumulative burden to track the lifelong impact of 168 chronic health conditions on 5,522 St. Jude adult survivors of childhood cancer, most enrolled in the St. Jude Lifetime Cohort study (St. Jude LIFE), and 272 community volunteers with no history of pediatric cancer. By age 50, the average pediatric cancer survivor had 17.1 chronic health conditions, including 4.7 that were severe/disabling, life-threatening or fatal. In contrast, the community volunteers averaged 9.2 chronic health conditions, of which 2.3 fell into those same categories. “The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions, some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said first and corresponding author Nickhill Bhakta, M.D., an assistant member of the St. Jude Department of Global Pediatric Medicine. “The results suggest that childhood cancer survivors may benefit from the integrated, specialized health care delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems,” he said. The models include patient-centered medical homes, which aim to provide patients with comprehensive, coordinated services to address their medical and psychosocial needs. Currently, most adult survivors rely on primary care providers, in consultation with medical specialists, to coordinate care and ensure survivors receive recommended health screenings and follow-up care. The U.S. is home to more than 420,000 childhood cancer survivors, a number that is expected to grow as cure rates improve and survivors live longer. St. Jude LIFE is a unique resource to identify, understand and begin to address the challenges survivors face. In this ongoing study, long-term childhood cancer survivors treated at St. Jude periodically return to campus for comprehensive clinical and functional tests and screenings. “This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by health care providers to disentangle and manage—time that community providers are unlikely to have,” Bhakta said. Previous studies from researchers at St. Jude and other centers have reported that survivors often have unrecognized and unmet health care needs. Historically, survivors have also struggled to maintain health insurance and access needed care. The study is the first to quantify and compare the cumulative burden of chronic disease in a clinically assessed group of childhood cancer survivors and community volunteers matched for age and sex. Cumulative burden was calculated using data from the comprehensive clinical assessments of 3,010 survivors enrolled in St. Jude LIFE and the 272 community volunteers. Rather than counting a health problem once at diagnosis, cumulative burden tracks health conditions as they occur, capturing subsequent heart attacks, cancer diagnoses or other recurring conditions that are missed by other statistical approaches. The analysis also included 21 variables related to survivors’ cancer treatment, including cumulative doses of radiation and chemotherapy agents. Statistical methods were used to calculate the cumulative burden of an additional 2,512 long-term St. Jude cancer survivors. The survivors’ cumulative burden varied substantially, based in part on survivors’ age at diagnosis, cancer treatment and treatment era. Second cancers, cardiovascular disease and endocrine disorders were significant contributors to survivors’ cumulative burden. A Web-based tool for calculating the cumulative burden of individual patients is in development to help patients and health care providers better understand and manage health care for individuals. Cumulative burden should also help researchers designing clinical trials understand the risks and benefits of different treatment strategies. The senior authors are Leslie Robison, Ph.D., chair of the St. Jude Department of Epidemiology and Cancer Control, and Yutaka Yasui, Ph.D., a member of the St. Jude Department of Epidemiology and Cancer Control. The other authors are Kirsten Ness, Malek Baassiri, Hesham Eissa, Frederick Yeo, Wassim Chemaitilly, Matthew Ehrhardt, Johnnie Bass, Michael Bishop, Kyla Shelton, Lu Lu, Sujuan Huang, Zhenghong Li, Eric Caron, Jennifer Lanctot, Carrie Howell, Timothy Folse, Daniel Green, Daniel Mulrooney, Gregory Armstrong, Kevin Krull, Tara Brinkman, Raja Khan, Deo Srivastava and Melissa Hudson, all of St. Jude; Qi Liu of the University of Alberta, Canada; and Vijaya Joshi, of the University of Tennessee Health Science Center, Memphis. The study was supported in part by grants (CA195547, CA21765) from the National Cancer Institute, the St. Baldrick’s Foundation and ALSAC, the fundraising and awareness organization of St. Jude.
People with severe emphysema may breathe better after a minimally invasive procedure that places valves in the airways leading to diseased portions of their lungs, according to a randomized, controlled trial published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine. In “A Multicenter RCT of Zephyr® Endobronchial Valve Treatment in Heterogeneous Emphysema (TRANSFORM),” European researchers report results from the first multicenter randomized, controlled trial comparing the therapeutic approach developed by Pulmonx Corp. to standard of care. The one-way Zephyr® valve keeps air from entering diseased regions of the lung, allowing healthier regions to expand and function better. The authors note that previous studies of the valves, which are placed using a bronchoscope, found that for patients with severe emphysema, this minimally invasive therapy represents an alternative to lung volume reduction surgery. Patients undergoing endobronchial valve (EBV) therapy appear to experience similar improvements in lung function, shortness of breath, exercise intolerance and quality of life--without the morbidity and mortality previously associated with surgery. “EBVs have been shown to work in single center trials, but these studies tend to be performed at centers, and by physicians, with considerable experience, so the results may not be generalizable to other centers,” said lead study author Samuel V. Kemp, MD, a respiratory physician and an expert in Interventional bronchoscopy at Royal Brompton Hospital, in the U.K. “What is interesting about this multicenter trial is that the results are at least as good as the single center studies, even though some of the investigators were new to the technique.” Zephyr® valves have been certified for human use in Europe, but are not widely available to patients in all health care systems. The valves have not been approved in the U.S., though a clinical trial of the technology is underway to support an application to the Food and Drug Administration for approval. The European study enrolled 97 patients from 17 medical centers. The patients were all ex-smokers over the age of 40 who had severe heterogeneous emphysema (emphysema isolated to certain parts of the lung). Sixty-five were randomly assigned to the EBV arm. On average, they received four valves to cut off diseased portions of their lungs that did not receive collateral ventilation (ventilation of the alveoli through passages that bypass the normal airways). The other patients received standard of care based on each medical center’s protocols for caring for patients following bronchoscopy. The researchers found: After three months, 55.4 percent of the EBV group had a ≥ 12 percent improvement (the minimum improvement the authors decided in advance would be clinically significant) in FEV1, the amount of air that can be forcefully exhaled in one second, compared to 6.5 percent of controls. After six months, the percentage of those in the EBV group meeting the minimum FEV1 improvement were 56.3 percent, compared to 3.2 percent of controls. The average increase in FEV1 in the EBV group was nearly 30 percent. After six months, secondary endpoints among those in the EBV group were also clinically and statistically significant, including being able to walk nearly 80 meters longer in six minutes, retaining 750 fewer milliliters of air (residual volume) upon maximum expiratory effort, exhibiting less shortness of breath on the modified Medical Research Council Dyspnea Scale and reporting higher quality of life on the St. George’s Respiratory Questionnaire. The most common adverse event in the EBV group was a collapsed lung, which occurred in 29.2 percent of the patients. After six months, 30 of the 32 participants in the control arm left the study and received EBV therapy. The authors will continue to follow those who received EBVs for up to two years. “There has been a lot of skepticism about valves, largely owing to poorly designed early trials,” Dr. Kemp said. “TRANSFORM proves that EBVs are a safe and effective treatment for appropriately selected patients with severe emphysema. “For these patients, the benefits of EBVs are far greater than standard medical therapy, so it is important that patients be assessed by a multidisciplinary team to determine if this treatment will help them breathe better.” Dr. Kemp added that for those patients with collateral ventilation, valves are not suitable and patients should be considered for lung volume reduction surgery. The study was sponsored and funded by Pulmonx Corporation, Redwood City, California, U.S.A. Contact for Article Samuel V. Kemp, MD S.Kemp@rbht.nhs.uk +44 207 351 8021
Researchers at UC Davis and other institutions have shown that mothers who take recommended amounts of folic acid around conception might reduce their children’s pesticide-related autism risk. In the study, children whose mothers took 800 or more micrograms of folic acid (the amount in most prenatal vitamins) had a significantly lower risk of developing autism spectrum disorder (ASD) – even when their mothers were exposed to household or agricultural pesticides associated with increased risk. The study appears today in the journal Environmental Health Perspectives. “We found that if the mom was taking folic acid during the window around conception, the risk associated with pesticides seemed to be attenuated,” said Rebecca J. Schmidt, assistant professor in the Department of Public Health Sciences and first author on the paper. “Mothers should try to avoid pesticides. But if they live near agriculture, where pesticides can blow in, this might be a way to counter those effects.” In the paper, which used data from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study, researchers looked at 296 children between 2 and 5 who had been diagnosed with ASD and 220 who had developed typically. Mothers were interviewed about their household pesticide exposure during pregnancy, as well as their folic acid and B vitamin intake. The team also linked data from California Pesticide Use reports, which provide important details about agricultural spraying, with the mothers’ addresses. Mothers who took less than 800 micrograms and encountered household pesticides had a much higher estimated risk of having a child who developed an ASD than moms who took 800 micrograms of folic acid or more and were not exposed to pesticides. The associated risk increased for women exposed repeatedly. Women with low folic acid intake who were exposed to agricultural pesticides during a window from three months before conception to three months afterward also were at higher estimated risk. “Folic acid intake below the median and exposure to pesticides was associated with higher risk of autism than either low intake or exposure alone,” said Schmidt, a UC Davis MIND Institute faculty member. “The mothers who had the highest risk were the ones who were exposed to pesticides regularly.” While folic acid did reduce the associated risk of a child developing autism, it did not entirely eliminate it. “It would be better for women to avoid chronic pesticide exposure if they can while pregnant,” Schmidt said. The authors caution that this is a case-control study that relied heavily on the participants’ memories. In addition, they have yet to establish a causal link. However, these results certainly warrant larger studies to validate them. The team is also eager to investigate the mechanisms that contribute to folic acid’s possible protective effects. “Folate plays a critical role in DNA methylation (a process by which genes are turned off or on), as well as in DNA repair and synthesis,” said Schmidt. “These are all really important during periods of rapid growth when there are lots of cells dividing, as in a developing fetus. Adding folic acid might be helping out in a number of these genomic functions.” Other researchers included Janie F. Shelton, Lora Delwiche, Robin L. Hansen, Sally Ozonoff, Deborah H. Bennett, Irva Hertz-Picciotto and Daniel Tancredi at UC Davis; Vladimir Kogan and Heather E. Volk at UCLA; and Claudia C. Ma Erin and C. McCanlies at the National Institute for Occupational Safety and Health. This study was funded by the National Institute of Environmental Health Sciences, National Institute of Child Health and Human Development, part of the National Institutes of Health (R21-ES021330, R01-ES015359, P01-ES11269, 2K12HD051958, R21-ES19002, P30-ES023513 and U54-HD079125); The Environmental Protection Agency STAR program (R-42 829388 & R833292) and the UC Davis MIND Institute.
Frequent e-cigarette use does help smokers quit — a finding that Georgetown Lombardi Comprehensive Cancer Center researchers say supports the use of e-cigarettes as a cessation aid for those trying to quit cigarette smoking. But, they note, an examination of a recent national survey uncovers important clues about who’s successful at quitting and why. The findings, published in Nicotine & Tobacco Research, examined a national survey of more than 24,500 current or recent former cigarette smokers, which is the largest sample of smokers studied to date. This study, along with a July study published in the BMJ, provide some of the strongest evidence so far on the link between use of e-cigarettes and cessation, says the study’s lead author David Levy, PhD, professor of oncology at Georgetown Lombardi. However, Levy notes, there are important nuances in the data that impact a person’s success in quitting cigarette smoking. “Both cigarette quit attempts and quit success were directly related to the number of days of e-cigarette use,” Levy explains. “The odds of quit success increased by 10 percent with each additional day of e-cigarette use.” The data also show that among those making at least one quit attempt, quit success was lower among individuals who had used e-cigarettes at some point in the past, but higher among those with at least 5 days of e-cigarettes use in the last month. The data is drawn from a special tobacco use survey that, since 1992-1993, has been taken every 3-4 years as part of a population survey conducted monthly by the U.S. Census Bureau. The latest tobacco use survey, taken from 2014-2015, was co-sponsored by the National Cancer Institute and the U.S. Food and Drug Administration. This survey, the Tobacco Use Supplement to the Current Population Survey (TUS-CPS), is designed to track long-term trends in tobacco use, cessation attempts and tobacco-related policies. All states are represented, and participants are interviewed either by telephone or in person. The latest TUS-CPS consisted of three samples collected in July 2014, and in January and May of 2015. These samples included more than 150,000 respondents. Levy and his Georgetown Lombardi colleagues examined the relationship between frequencies of e-cigarette use, cigarette quit attempts and cigarette abstinence. Because of the dates of the survey, it includes the more current types of e-cigarettes that are more effective at delivering nicotine. "Our findings are consistent with randomized trials and those observational studies that measure frequency of e-cigarette use. These results support the use of e-cigarettes — especially, consistent use — as an effective smoking cessation aid. Since e-cigarettes are generally estimated to have a small proportion of the mortality risks of cigarettes, this represents an important life-saving intervention that doctors can recommend when other forms of treatment fail,” says Levy. Study co-authors include Zhe Yuan, MS, Yuying Luo, MS, and David B. Abrams, PhD, all from Georgetown Lombardi Comprehensive Cancer Center. The authors report having no personal financial interests related to the study. The study was funded by grants from the National Institute of Drug Abuse (R01DA036497) and the National Cancer Institute (P01-CA200512). About Georgetown Lombardi Comprehensive Cancer Center Georgetown Lombardi Comprehensive Cancer Center is designated by the National Cancer Institute as a comprehensive cancer center — the only cancer center of its kind in the Washington, DC area. A part of Georgetown University Medical Center and MedStar Georgetown University Hospital, Georgetown Lombardi seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. About Georgetown University Medical Center Georgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC’s mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.
Sleep apnea, left untreated for even a few days, can increase blood sugar and fat levels, stress hormones and blood pressure, according to a new study of sleeping subjects. A report of the study’s findings, published in the August issue of The Journal of Clinical Endocrinology & Metabolism, adds further support for the consistent use of continuous positive airway pressure (CPAP), a machine that increases air pressure in the throat to keep the airway open during sleep. “This is one of the first studies to show real-time effects of sleep apnea on metabolism during the night,” says Jonathan Jun, M.D., assistant professor of medicine at the Johns Hopkins University School of Medicine and the paper’s senior author. Obstructive sleep apnea (OSA) affects 20 – 30 percent of adults, according to studies published in the American Journal of Epidemiology and Lancet Respiratory Medicine. It occurs when the upper airway closes off during sleep, temporarily interrupting breathing. While it is known that OSA is associated with risks for diabetes and heart disease, there has been no consensus on whether OSA is a cause of these disorders or just a marker of obesity, which predisposes one to diabetes and heart disease. Previous metabolic studies in patients with OSA, the Johns Hopkins researchers say, usually collected data while participants were awake, thus obtaining only a snapshot of OSA’s aftermath, not the actual sleep period when OSA occurs. To better understand how OSA affects metabolism, researchers measured free fatty acids in the blood, glucose, insulin and cortisol (a stress hormone) while participants slept in a sleep laboratory at the Johns Hopkins Bayview Medical Center. Participants’ brain waves, blood oxygen levels, heart rates and breathing, along with eye and leg movements, were also recorded each night of the study. In total, Jun and colleagues drew blood samples from 31 patients with moderate to severe OSA and a history of regular CPAP use for two nights. The researchers drew samples every 20 minutes starting at 9 p.m. and until 6:40 a.m. Every participant spent one night at the lab with CPAP or after CPAP had been stopped for two nights, in random order, separated by one to four weeks. The average age of all participants was 50.8 years old and the average body mass index indicated obesity, a common characteristic of those with sleep apnea. Two-thirds of the study group was male and a quarter had a history of non-insulin dependent diabetes. Some 22.6 percent of participants were African American, 9.7 percent Asian, 64.5 percent Caucasian and 3.2 percent Hispanic. Jun and colleagues found that CPAP withdrawal caused recurrence of OSA associated with sleep disruption, elevated heart rate and reduced blood oxygen. CPAP withdrawal also increased levels of free fatty acids, glucose, cortisol and blood pressure during sleep. The more severe the OSA, the more these parameters increased. In addition, glucose increased the most in patients with diabetes. Increases in fatty acids, glucose and cortisol have all been linked to diabetes. The Johns Hopkins team also found that blood pressure increased and the arteries showed signs of stiffness in the morning without CPAP. Over time, increased blood pressure and vascular stiffness can contribute to cardiovascular disease. Jun emphasized that the study was limited by studying people with severe OSA and obesity, thus limiting the ability to apply the findings to all OSA patients. The researchers also did not compare CPAP use to a sham CPAP control group to exclude a potential placebo effect. But Jun says that the study provides further evidence that sleep apnea isn’t just a manifestation of obesity, diabetes and cardiovascular disease — it can directly aggravate these conditions. They are continuing to recruit patients in order to answer more questions about which patients are most vulnerable to the impacts of OSA. This study emphasizes the importance of CPAP therapy for OSA to prevent its metabolic and cardiovascular consequences. Sometimes, patients with OSA have a hard time tolerating CPAP. It is important that these patients contact a sleep specialist who can assist them with CPAP use, or who can recommend alternative therapies. Other authors on this paper include Swati Chopra, Aman Rathore, Haris Younas, Luu V. Pham, Aleksandra Beselman, Il-Young Kim, Robert R. Wolfe and Vsevolod Y. Polotsky of The Johns Hopkins University; Chenjuan Gu of the Shanghai Jiao Tong University School of Medicine; and Jamie Perin of the University of Arkansas for Medical Sciences. Funding for the research was provided by the American Academy of Sleep Medicine Foundation Junior Faculty Award (106-JF-14), the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072488), and the National Heart, Lung, and Blood Institute (1K08HL109475, R01HL133100, R01HL128970).