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News Article | May 1, 2017
Site: www.futurity.org

More than 40 percent of survivors of acute respiratory distress syndrome (ARDS) who had jobs were unemployed a year after leaving the hospital, losing an average of $27,000 in pay, a new study estimates. ARDS affects approximately 200,000 Americans every year. Survivors often have long-lasting cognitive dysfunction, mental health issues, or physical impairments, any of which can affect their ability to hold down a job. “Health care providers need to start asking themselves, ‘What can we do to help patients regain meaningful employment,’ and not just concern ourselves with their survival,” says Dale Needham, professor of physical medicine and rehabilitation at Johns Hopkins University. ARDS is a lung condition often caused by severe infection or trauma and marked by fluid buildup in the lungs’ air sacs. The resulting damage leads to a substantial decrease in oxygen reaching the bloodstream and rapidly developing difficulty with breathing. Patients are usually hospitalized and placed on a life-supporting ventilator. One important goal of the study, researchers say, is to better identify specific risk factors for joblessness and to inform future interventions aimed at reducing joblessness after ARDS. “Multiple studies have suggested that joblessness is common in people who survive ARDS,” says Biren Kamdar, assistant professor of medicine at the University of California, Los Angeles and the study’s first author. “But to our knowledge, none have carefully tracked those who returned to work or subsequently lost their jobs, performed an in-depth analysis of risk factors for joblessness, and evaluated the impact of joblessness on lost earnings and health care coverage.” The research was part of a larger long-term study of ARDS survivors who have been patients at 43 hospitals across the United States. Investigators recruited 922 survivors and did telephone interviews at six and 12 months after the onset of ARDS. Each survivor was asked about employment, hours per week, how soon after hospital discharge they returned to work, perceived effectiveness at work, and any major change in occupation. Researchers estimated lost earnings using age- and sex-matched wage data from the US Bureau of Labor Statistics. Of the 922 survivors, 386 (42 percent) were employed prior to ARDS. The average age of these previously employed survivors was 45; 4 percent were 65 or older. Overall, previously employed survivors were younger, predominantly male, and had fewer pre-existing health conditions compared with survivors not employed before ARDS. Of the 379 previously employed patients who survived to the 12-month follow-up, 44 percent were jobless by that time. Some 68 percent of survivors had returned to work at some point during the 12-month follow-up period, but many with fewer hours or reduced on-the-job effectiveness. About 24 percent then lost their jobs. Throughout the 12-month follow-up period, non-retired jobless survivors had an average estimated earnings loss of about $27,000 each, or 60 percent of their pre-ARDS annual earnings. The findings also show a substantial decline in private health insurance coverage (from 44 to 30 percent) and a rise in Medicare and Medicaid enrollment (33 to 49 percent). “We believe that ARDS survivors are often jobless due to a combination of physical, psychological, and cognitive impairments that may result, in part, from a culture of deep sedation and bed rest that plagues many ICUs,” says Needham, senior author of the study published in the American Journal of Respiratory and Critical Care Medicine. “Perhaps if we can start rehabilitation very early, while patients are still on life support in the intensive care unit, getting them awake, thinking, and moving sooner, this may result in greater cognitive and physical stimulation and improved well-being.” Other researchers involved in the study were from Johns Hopkins, UCLA and Intermountain Medical Center in Utah. Funding came from the National Heart, Lung and Blood Institute, the ARDS Network and the NIH-funded UCLA Clinical and Translational Science Institute.


News Article | April 28, 2017
Site: www.techtimes.com

The stubborn fat lying around one’s midsection is not only unsightly and annoying but is also a health risk. According to a new study, people with a normal body mass index or BMI but carry excess weight around their middle have the highest death risk from any cause, compared with the overweight or obese who carry weight somewhere else. A team from Loughborough University in the United Kingdom tracked over 42,000 participants every year for a decade based on the annual Health Survey for England, and Scotland’s Health Survey. They set out to see if a large-scale data analysis would confirm earlier findings from smaller studies, which noted that normal-weight people with stomach fat fared worst even against the overweight with the same central obesity. In the past, researchers argued that BMI is no longer the most reliable way to predict one’s health risks. They came up with something potentially more telling, namely the waist-to-hip ratio or one’s waist measurement divided by hip measurement. A resulting high ratio is deemed troublesome, even if one’s weight is within normal range. In 2011, a study from the Mayo Clinic discovered that excess weight carried in one’s midsection could result in diabetes, stroke, and cardiovascular conditions. Based on BMI as well as waist-to-hip ratio, the new study categorized the subjects into different groups: normal weight; normal weight with fat in midsection; overweight; overweight with fat in midsection; obese; and obese with fat in midsection. Compared with normal-weight subjects without central obesity, only normal weight and obese subjects with central obesity had the greater risk for so-called “all-cause mortality.” Never mind what their BMI was — all subjects with tummy fat had increased risk for cardiovascular death. "It is yet further evidence that even if you are within a 'healthy' BMI range but you carry weight around your stomach your health is still at risk,” said study author and professor Mark Hamer in a statement, calling for those with central obesity to start taking steps toward fat reduction. The findings were discussed in the journal Annals of Internal Medicine. Obesity remains the leading cause of premature death among Americans, despite the general scope of advanced treatment. It steals 47 percent more life-years than tobacco when compared with other conditions, a new study stated. In recent years, however, researchers have been more critical of belly fat, especially that which is stored inside the abdominal cavity. A study from last year, for instance, showed that the density of stomach fat is as significant as how much fat is present around someone’s midsection. "What's really interesting is that we show that an increase in the amount of stomach fat and a lower density fat is associated with worse heart disease risk factors — even after accounting for how much weight was gained," said lead researcher Dr. Caroline Fox, who is also former senior investigator for the National Heart Lung and Blood Institute. While both levels of fat under skin and fat accumulated inside the abdominal cavity adversely affected heart health, the latter — also known as visceral adipose fat — increased cardiovascular risk even worse. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


News Article | April 6, 2017
Site: www.scientificcomputing.com

The American Heart Association Precision Medicine Platform -- a global, secure data discovery platform, recently developed in collaboration with Amazon Web Services (AWS) -- is now open for use. Researchers, physicians, computational biologists, computer engineers and trainees from around the globe can leverage this cloud-based resource to access and analyze volumes of cardiovascular and stroke data to accelerate the care of patients at risk of the number one killer in the United States and a leading global health threat. The AHA Institute for Precision Cardiovascular MedicineTM is calling on all cardiovascular and stroke dataset owners and stewards to share their data as the first step in acquiring all the pieces needed to treat and prevent heart failure, stroke, coronary artery disease, atrial fibrillation and other cardiovascular diseases. Data from clinical trials, long-running epidemiologic studies, registries and real-time health data acquired through wearable devices and technology is sought. "We have blown away the barriers and welcome all to join this game-changing platform that promotes us working together as one community to ultimately benefit patients worldwide," said Jennifer Hall, PhD, the AHA's Chief of the Institute for Precision Cardiovascular Medicine. "The platform provides an opportunity to learn, search and discover in new and efficient ways, and we will keep working with the community to weave in new diverse data to help us drill deeper and enrich our understanding." Several organizations are leading the way toward the future of open data by contributing their information to the secure platform, including AstraZeneca, Cedars-Sinai Heart Institute, Dallas Heart Study, Duke Cardiovascular Research Institute, Intermountain Health, the International Stroke Genetics Consortium, the National Heart, Lung and Blood Institute (NHLBI) and Stanford University. "The increasing breadth and depth of medical data presents a tremendous opportunity to generate more nuanced and precise pre-diagnoses. However, leveraging this data requires tools capable of integrating data of diverse origin. The AHA Precision Medicine Platform can empower researchers with both the framework and tools to ease the burdens of data harmonization, amplifying the insight available from their own data." Said Gabriel Musso, PhD, VP Life Sciences, BioSymetrics Inc., who has been actively using the platform during the initial phase. The AHA Precision Medicine Platform is the only resource of its kind focused on cardiovascular diseases and stroke. "I am so excited for the potential the AHA Precision Medicine Platform brings for doing research across data sets to find consistent research results, and replicate and confirm research," said early adaptor Laura M. Stevens, a Predoctoral National Library of Medicine Fellow in the computational biosciences program at the University of Colorado Anschutz Medical School. "The platform makes big data analyses much quicker and easier. It's a great foundation for implementing precision medicine and research in a clinical setting. I can't wait to see where this will take us as a research community." Researchers are not charged for accessing the data but will pay a fee for cloud computing capabilities based on the current AWS model. Any revenue from cloud-based computing will be used to fund AHA's research initiatives. "By working together on datasets we have the ability to test the speed, agility and transparency of research," said Hall. "With your data and your efforts, the AHA Precision Medicine Platform can help enable your discoveries of novel underlying causal factors of heart failure, new diagnostic biomarkers to predict stroke, or exponential new approaches to precision care for those with cardiovascular diseases and stroke." Through the tool, the AHA reaches across the government, academic, industry, and patient communities to deepen data resources and spur research opportunities with an aim to transform cardiovascular research and patient care. To further foster research aimed at reversing and preventing cardiovascular diseases and stroke, the AHA Institute for Precision Cardiovascular Medicine also offers a variety of grant opportunities for scientists and researchers from many different fields of study. The application process for several grants is currently open.


News Article | May 2, 2017
Site: www.eurekalert.org

Less than half of individuals with peripheral artery disease, which is a narrowing of arteries to the limbs, stomach and head, are treated with appropriate medications and lifestyle counseling. These findings highlight the need to improve the quality of care for this high-risk group of individuals. Peripheral artery disease affects an estimated 200 million people around the world. It is becoming more prevalent due to the world's aging population, which is at higher risk for the disease. People with this disease are also at high risk for coronary heart disease, heart attacks and strokes. Peripheral artery disease causes claudication, which is cramping and pain in the legs and buttocks during physical activity. The disease can also lead to gangrene and limb amputation. From a societal perspective, the consequences of the disease are significant. It is, however, easily diagnosed and can be managed with lifestyle changes and medication. The researchers used data from 1,982 outpatient visits from people with the disease that was taken from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, a nationally representative assessment of office-based and hospital outpatient department practices. They found an average of 3.8 million ambulatory visits in the United States for peripheral artery disease over eight years. Comorbid coronary artery disease, which is a combination of both peripheral artery and coronary artery disease, was present in 24.1 percent of the visits. Medication use was low for cardiovascular prevention and symptoms of claudication. The researchers also found that aspirin was used in only 37.8 percent of the cases; statins were prescribed 35 percent of the time; blood pressure medication use was at 31.1 percent; and cilostazol was prescribed in 5 percent of visits. Cilostazol is an FDA-approved medication for treating claudication in patients with peripheral artery disease. Counseling on diet or exercise was provided in only 20.1 percent of visits. Smoking cessation counseling or medication was given only 36.3 percent of the time to current smokers with peripheral artery disease. There was no significant change in medication use or lifestyle counseling over time. Compared to visits for individuals with peripheral artery disease alone, patients with both peripheral artery disease and coronary artery disease were more likely to be prescribed antiplatelet therapy, statins, blood pressure medications, and counseled for smoking cessation. The findings clearly show underuse of cardiovascular prevention medication in individuals with peripheral artery disease. Because of this underuse, a considerable number of individuals with the disease remain at increased risk for adverse outcomes. This study is a "call to action" to identify and implement effective physician-targeted and patient-targeted strategies aimed at improving quality of care. These strategies should take advantage of recent advances in behavior change, including leveraging an individual's social support network to help them make lifestyle changes, and providing physicians with feedback about the quality of care they provide to patients with peripheral artery disease. Joseph Ladapo of UCLA and Jeffrey Berger of New York University. The study is published online by the Journal of the American College of Cardiology. The National Heart and Lung Blood Institute of the National Institutes of Health (R01HL114978), a K23 Career Development Award (K23 HL116787) from the National Heart, Lung and Blood Institute, and the Robert Wood Johnson Foundation (74140) funded this research. Berger receives research funding from Astra Zeneca and served on the Executive Committee for the EUCLID trial of antiplatelet therapy in patients with peripheral artery disease. He also receives consulting fees from Janssen and Merck. Ladapo has no disclosures.


News Article | April 17, 2017
Site: www.eurekalert.org

One of the top ten killers for men older than 55 is the target of Clemson University research that could lead to a new life-saving therapy and a better way of telling whether surgery is necessary. Naren Vyavahare, who holds the Hunter Endowed Chair, has received $1.47 million from the National Institutes of Health to advance research into abdominal aortic aneurysms. When they rupture, the aneurysms are fatal 75-90 percent of the time without immediate hospitalization, he said. About 200,000 people in the United States are diagnosed each year with an abdominal aortic aneurysm, often called AAA, according to the Society for Vascular Surgery. While Vyavahare's work is at least 10 years from market, he hopes it could eventually ease anxiety and prevent surgery for thousands of patients. More than 70,000 surgeries are performed each year, he said. "When someone finds an aneurysm, it's a time bomb sitting in your stomach," Vyavahare said. "Our research could lead to a new therapy. Right now, the only therapy is a vascular graft, which is surgical treatment. We are thinking, 'Can a patient have a systemic therapy, such as an injection they can take?'" Vyavahare has two aims in the research, both using specially engineered nanoparticles that are 250-fold smaller than the width of a human hair and circulate through the bloodstream. One aim is to develop a new treatment. The nanoparticles would attach to the aneurysm and deliver the chemical compound pentagalloyl glucose (PGG). Previous studies in animals have shown that PGG stabilizes and shrinks aortic aneurysms, making them less likely to rupture. Another aim is to improve diagnosis. Vyavahare is also using gold nanoparticles to develop a new way of creating medical images that could identify aneurysms' weak spots, helping tell if surgery is necessary. The gold nanoparticles would accumulate at the damaged tissue so that a CT scan could help give a better diagnosis of weakened tissue. "Imaging can give you the option--maybe you should go for therapy or maybe you need surgery if it's too weak and you can't wait," Vyavahare said. An abdominal aortic aneurysm is a balloon-like bulge in the aorta, the body's main artery. It runs from the heart to the abdomen, distributing oxygenated blood throughout the body. An aneurysm is caused by a thinning and weakening of the vessel wall. High blood pressure, high cholesterol, hardened arteries and smoking are risk factors for aortic aneurysm, according to the Centers for Disease Control and Prevention. The statistics are grim when the aneurysm ruptures. It's the 15th leading cause of death in the country, and the 10th leading cause of death in men older than 55, according to the Society for Vascular Surgery. The nanoparticles in Vyavahare's research are coated with an elastin antibody, causing them to attach to the degraded elastin, a protein in the aneurysm. Vyavahare described elastin as the "rubber band of life" and said it's the body's version of elastic material, making it possible for arteries to push blood forward. Inflammatory conditions in aneurysms lead to elastin degradation. When carried by nanoparticles, a small amount of PGG can be used to stabilize and restore elastin. Without the nanoparticles, so much PGG would be needed that it would be toxic. Martine LaBerge, chair of the Department of Bioengineering, said the grant, an R01, was well-deserved. "Dr. Vyavahare is a leading researcher in his field with more than 20 years' experience," she said. "His background in chemistry combined with his clinical experience uniquely qualifies him to lead this project." Doctors face difficult decisions when deciding whether the risk of aneurysm rupture justifies surgery because patients are often elderly and have other health issues. Vascular grafts are typically recommended when aneurysms reach 5 centimeters in diameter. The diameter increase is monitored with ultrasounds and CT scans that are often enhanced with large amounts of iodinated contrast agents. The toxicity of those agents have been debated, and the scans do not provide information about the extent of aortic wall damage. Vyavahare sees the gold nanoparticles as a promising substitute for the iodinated contrast agents. Only a small amount of gold nanoparticles would be needed, he said. They would go only to the degraded elastin, allowing doctors to get vital information about the extent of damage. Vyavahare's work has also raised hopes that nanoparticles could be used to treat other ailments involving elastin degradation, including chronic obstructive pulmonary disease, commonly called COPD. A Clemson group that included Vyavahare used the nanoparticles to successfully deliver the drug doxycycline to rats with emphysema, which is often a part of COPD. The research showed promise as a way of controlling inflammation, halting further damage to the lungs. That research was reported in the journal Pulmonary Pharmacology & Therapeutics. The next step is to try the method in larger animals, Vyavahare said. Anand Gramopadhye, dean of the College of Engineering, Computing and Applied Sciences, said that Vyavahare's research is helping engineer better medicines, one of the grand challenges identified by the National Academy of Engineering. "The award is a testament to his innovative approach, years of hard work, and the results he has produced," Gramopadhye said. "I congratulate Dr. Vyavahare on this well-deserved grant." Research supported in this publication was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health under Award Number 1R01HL133662-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


News Article | May 5, 2017
Site: www.rdmag.com

A new discovery in mice has researchers confident they can develop new medications to help combat mid-life obesity and ultimately decrease the rates of heart disease, diabetes and other illnesses. A team of scientists led by the National Institutes of Health have pinpointed an enzyme in mice that could upend current theories as to why people gain weight as they age, and might lead to new effective weight-loss medications. “Our society attributes the weight gain and lack of exercise at mid-life [approximately 30-60 years] primarily to poor lifestyle choices and lack of will power, but this study shows that there is a genetic program driven by an overactive enzyme that promotes weight gain and loss of exercise capacity at mid-life,” Dr. Jay Chung, Ph.D., the lead author of the study and the head of the Laboratory of Obesity and Aging Research at the National Heart, Lung and Blood Institute (NHLBI), said in a statement. The enzyme—called DNA-dependent protein kinase (DNA-PK)—increases in activity with age and promotes the conversion of nutrients to fat and decreases the number of mitochondria, tiny organelles in the cells that turn fat into energy to fuel the body. The average adult in the U.S. gains 30 pounds between the age of 20 and 50, despite the fact that food intake generally decreases during this period. Mitochondria is also found in abundance among young people but decreases as people age. By reducing DNA-PK activity the research team believes fat accumulation will decrease and the mitochondria number will increase. During the experiment they administered an inhibitor that blocked the enzyme in one group that were fed high-fat foods, while withholding it in another group and found a 40 percent decrease in weight gain in the group that received the inhibitor. The inhibitor also boosted mitochondrial content in skeletal muscle and increased aerobic fitness in obese and middle aged mice while reducing the incidence of obesity and type-2 diabetes. “Our studies indicate that DNA-PK is one of the drivers of the metabolic and fitness decline that occurs during aging, which makes staying lean and physically fit difficult and increases susceptibility to metabolic diseases like diabetes,” Chung said. “The identification of this new mechanism is very important for improving public health. “The study opens the door to the development of a new type of weight-loss medication that could work by inhibiting DNA-PK activity,” he added


News Article | April 19, 2017
Site: www.eurekalert.org

The Clinical Research Forum, a national organization of senior researchers and thought leaders from the nation's leading academic health centers, selected two studies headed by University of Chicago researchers as among the three best clinical research papers published in 2016. These awards honor outstanding clinical research and identify major advances resulting from the nation's investment in improving the health of its citizens. Ten award winners were chosen for their innovation and creativity, advancement of science in a specific area, contribution to understanding human disease or physiology, and potential impact upon the diagnosis, prevention and treatment of disease. The Herbert Pardes Clinical Research Excellence Award is the Clinical Research Forum's highest honor. It is awarded to the research study that best exemplifies the spirit of the awards in that it shows a team science approach with a high degree of innovation and creativity, which advances science and has an impact upon human disease. The award comes with a cash prize of $5,000. This year, the Pardes Award went to a team headed by geneticist Carole Ober, PhD, professor and chairman of human genetics at the University of Chicago, and immunologist Anne Sperling, PhD, associate professor of medicine at the University of Chicago. Their study, "Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children," was published Aug. 4, 2016, in the New England Journal of Medicine. The interdisciplinary team of researchers showed that substances in the house dust from Amish, but not Hutterite, homes were able to engage and shape the innate immune system (the body's front-line response to most microbes) in young Amish, but not Hutterite, children in ways that appear to suppress pathologic responses leading to allergic asthma. The Distinguished Clinical Research Achievement Awards are presented to the top two studies that demonstrate creativity, innovation, or a novel approach that demonstrates an immediate impact on the health and well-being of patients. These awards come with a cash prize of $3,500. One of those awards goes to a team led by pulmonologist John P. Kress, MD, professor of medicine at the University of Chicago, and Bhakti Patel, MD, clinical instructor of medicine at the University. Their study on the "Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial," was published May 15, 2016, in JAMA. It showed that using a transparent, air-tight helmet instead of a face mask helps critically ill patients breathe better and can prevent them from needing a ventilator. Patients with helmet ventilation had better survival and spent less time in the intensive care unit. The helmet "confers several advantages over the face mask," the authors note. It is less likely to leak. This enables the care team to increase air pressure into the helmet, which helps keep the airway and lungs open and improves oxygen levels. It is also more comfortable, easier to tolerate because it doesn't touch the face, and patients can see through it well enough to watch television, talk or read. Award recipients were recognized earlier this evening at the Clinical Research Forum's sixth annual awards ceremony on April 18 at the National Press Club in Washington, D.C. Members of the research teams will visit congressional representatives on Capitol Hill on Wednesday, April 19, to brief officials on their findings and the critical and necessary role of federal funding for clinical research. These studies reflect major work being conducted at nearly 60 research institutions and hospitals across the United States, as well as at partner institutions from around the world, according to the Clinical Research Forum. "The 2017 awardees represent the enormous potential that properly funded research can have on patients and the public," said Harry P. Selker, MD, MSPH, Chairman of the CR Forum Board of Directors. "It is our hope that the significance of these projects and their outcomes can help educate the public, as well as elected officials, on the important impact of clinical research on human health." Recognizing the need to celebrate our nation's clinical research accomplishments that involve both innovation and impact on human disease, the Clinical Research Forum conducts an annual competition to determine the ten outstanding research accomplishments in the United States. These major research advances represent a portion of the annual return on the nation's investment in the health and future welfare of its citizens. The mission of the Clinical Research Forum is to provide leadership to the national and clinical translational research enterprise and promote understanding and support for clinical research and its impact on health and healthcare. For more information, visit http://www. . The National Institutes of Health, the St. Vincent Foundation and the American Academy of Allergy, Asthma & Immunology Foundation supported the asthma study. Additional authors were Michelle Stein, Cara Hrusch, Catherine Igartua and Jack Gilbert from the University of Chicago; Donata Vercelli, Justyna Gozdz, Vadim Pivniouk, Julie Ledford, Mauricius Marques dos Santos, Julia Neilson, Sean Murray, Raina Maier and Fernando Martinez from the University of Arizona; Erika von Mutius of the Dr. von Hauner Children Hospital in Munich, Germany; Nervana Metwali and Peter Thorne from the University of Iowa; and Mark Holbreich, an allergist-immunologist in Indianapolis, Indiana. Funding for the helmet study was supplied by the National Heart Lung and Blood Institute. The helmets were purchased using funds from an unrestricted grant from the Daniel J. Edelman family. Additional authors were Krysta Wolfe, Anne Pohlman and Jesse Hall, all from the University of Chicago.


News Article | April 11, 2017
Site: www.medicalnewstoday.com

St. Jude Children's Research Hospital study examines origin of blood stem cells during development and offers clues for making "donor blood" in the laboratory for therapeutic use. Like private investigators on a stake out, St. Jude Children's Research Hospital scientists used patience and video surveillance-like tools to identify cells that trigger blood cell development. The findings offer clues for making blood-forming stem cells in the laboratory that may ultimately help improve access to bone marrow transplantation. "The research will likely open new avenues of investigation in stem cell biology and blood development and provide insight to aid efforts to make transplantable hematopoietic stem cells in the lab," said corresponding author Wilson Clements, Ph.D., an assistant member of the St. Jude Department of Hematology. The research appears in the journal Nature Cell Biology. Blood-forming stem cells are capable of making any type of blood cell in the body. They are also used in transplant therapies for cancers like leukemia or other blood diseases like sickle cell. They are starting to be used to deliver gene therapy. However, a shortage of suitable donors limits access to treatment, and efforts to produce blood from pluripotent stem cells in the laboratory have been unsuccessful. Pluripotent stem cells are the master cells capable of making any cell in the body. All blood-forming stem cells normally arise before birth from certain endothelial cells found in the interior blood vessel lining of the developing aorta. This process - including how endothelial cells are set on the path to becoming blood stem cells - is not completely understood. Clements and first author Erich Damm, Ph.D., a St. Jude postdoctoral fellow, have identified trunk neural crest cells as key orchestrators of the conversion of endothelial cells to blood stem cells. Trunk neural crest cells are made in the developing spinal cord and migrate throughout the embryo. They eventually give rise to a variety of adult cells, including neurons and glial cells in the sympathetic and parasympathetic nervous system, which control feeding, fighting, fleeing and procreating. Using time-lapse video, the researchers tracked the migration of neural crest cells in the transparent embryos of zebrafish. Zebrafish and humans share nearly identical blood systems, as well as the programming that makes them during development. After about 20 hours, the neural crest cells had reached the developing aorta. After hour 24, the migrating cells had cozied up to the endothelial cells in the aorta, which then turned on genes, such as runx1, indicating their conversion to blood stem cells. The investigators used a variety of methods to show that disrupting the normal migration of neural crest cells or otherwise blocking their contact with the aorta endothelial cells prevented the "birth" of blood stem cells. Meanwhile, other aspects of zebrafish development were unaffected. "Researchers have speculated that the endothelial cells that give rise to blood-forming stem cells are surrounded by a support 'niche' of other cells whose identity and origins were unknown," Damm said. "Our results support the existence of a niche, and identify trunk neural crest cells as an occupant." Adult bone marrow includes niches that support normal function and notably feature cells derived from trunk neural crest cells. The findings also suggest that trunk neural crest cells use a signal or signals to launch blood stem cell production during development. The researchers have eliminated adrenaline and noradrenaline as the signaling molecules, but work continues to identify the signaling proteins or small molecules involved. The research was supported in part by a grant (R00HL097) from the National Heart, Lung and Blood Institute of the National Institutes of Health; the March of Dimes; and ALSAC, the fundraising arm of St. Jude.


News Article | April 28, 2017
Site: www.eurekalert.org

According to a new multicenter study, nearly half of previously employed adult survivors of acute respiratory distress syndrome were jobless one year after hospital discharge, and are estimated to have lost an average of $27,000 in earnings. A summary of the research was published on April 28 in the American Journal of Respiratory and Critical Care Medicine. Acute respiratory distress syndrome (ARDS) is a lung condition often caused by severe infection or trauma, and marked by fluid build up in the lungs' air sacs. The resulting damage leads to a substantial decrease in oxygen reaching the bloodstream and rapidly developing difficulty with breathing. Patients are usually hospitalized and placed on a life-supporting ventilator. ARDS affects approximately 200,000 Americans every year. ARDS survivors often have long-lasting impairments such as cognitive dysfunction, mental health issues and physical impairments, all of which may affect employment. "This study is important and novel given its comprehensive evaluation of joblessness among almost 400 previously employed ARDS survivors from multiple sites across the U.S.," says Dale Needham, F.C.P.A, M.D., Ph.D., professor of medicine and of physical medicine and rehabilitation at the Johns Hopkins University School of Medicine and senior author of the study. "Multiple studies have suggested that joblessness is common in people who survive ARDS, but to our knowledge, none have carefully tracked those who returned to work or subsequently lost their jobs, performed an in-depth analysis of risk factors for joblessness, and evaluated the impact of joblessness on lost earnings and health care coverage," adds Biren Kamdar, M.D., M.B.A., M.H.S., assistant professor of medicine at the David Geffen School of Medicine at UCLA and the study's first author. One important goal of the research, the scientists say, is to better identify specific risk factors for joblessness and to inform future interventions aimed at reducing joblessness after ARDS. The new study was conducted as part of the ARDS Network Long-Term Outcome Study (ALTOS), a national multicenter prospective study longitudinally evaluating ARDS survivors recruited from 2006 to 2014, including patients from 43 hospitals across the U.S. For the analysis, the investigators recruited 922 survivors and interviewed them by telephone at six months and 12 months after the onset of their ARDS. Each survivor was asked about employment status, hours working per week, how long before they returned to work following hospital discharge, perceived effectiveness at work and major change in occupation. The research team estimated lost earnings using age- and sex-matched wage data from the U.S. Bureau of Labor Statistics. Individual survivors' matched wages were multiplied by the number of hours worked prior to hospitalization to determine potential earnings and by current hours worked to determine estimated earnings. Estimated lost earnings were calculated as the difference between estimated and potential earnings. Of the 922 survivors, 386 (42 percent) were employed prior to ARDS. The average age of these previously employed survivors was 45 years, 56 percent were male and 4 percent were 65 years or older. Overall, previously employed survivors were younger, predominantly male and had fewer pre-existing health conditions compared with survivors not employed before ARDS. Of the 379 previously employed patients who survived to 12-month follow-up, nearly half (44 percent) were jobless a year after discharge. Some 68 percent of survivors eventually returned to work during the 12-month follow-up period, but 24 percent of these survivors subsequently lost their jobs. Throughout the 12-month follow-up, non-retired jobless survivors had an average estimated earnings loss of about $27,000 each, or 60 percent of their pre-ARDS annual earnings. The research team also saw a substantial decline in private health insurance coverage (from 44 to 30 percent) and a rise in Medicare and Medicaid enrollment (33 to 49 percent), with little change in uninsured status. For the 68 percent of ARDS survivors who returned to work by the end of the follow-up year, the median time to return was 13 weeks after discharge. Of those, 43 percent never returned to the number of previous hours worked, 27 percent self-reported reduced effectiveness at work, and 24 percent later lost their jobs. The team found that older, non-white survivors, and those experiencing a longer hospitalization for their ARDS had greater delays in returning to work. Severity of illness and sex, however, did not affect time to return to work. "These results cry out for those in our medical field to investigate occupational rehabilitation strategies and other interventions to address the problem of post-discharge joblessness," Needham says. "Health care providers need to start asking themselves, 'What can we do to help patients regain meaningful employment,' and not just concern ourselves with their survival." "We believe that ARDS survivors are often jobless due to a combination of physical, psychological and cognitive impairments that may result, in part, from a culture of deep sedation and bed rest that plagues many ICUs. Perhaps if we can start rehabilitation very early, while patients are still on life support in the intensive care unit, getting them awake, thinking and moving sooner, this may result in greater cognitive and physical stimulation and improved well-being. This change in culture can occur and is part of regular clinical practice in our medical ICU at The Johns Hopkins Hospital." Other authors on this paper include Minxuan Huang, Victor D. Dinglas and Elizabeth Colantuoni of The Johns Hopkins University, Till M. von Wachter of the University of California at Los Angeles, and Ramona O. Hopkins of Intermountain Medical Center in Utah. Funding for this study is provided by the National Heart, Lung and Blood Institute (N01HR56170, R01HL091760 and 3R01HL091760-02S1), the ARDS Network trials (contracts HHSN268200536165C to HHSN268200536176C and HHSN268200536179C) and the UCLA Clinical and Translational Science Institute (CTSI) (NIH-National Center for Advancing Translational Science (NCATS) UCLA UL1TR000124 & UL1TR001881).

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