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Newswise — PHILADELPHIA – Cancer patients may one day be able to get their entire course of radiation therapy in less than a second rather than coming in for treatment over the course of several weeks, and researchers in the Abramson Cancer Center of the University of Pennsylvania have taken the first steps toward making it a reality. In a new report published today in the International Journal of Radiation Oncology, Biology, and Physics, researchers detail how they used proton radiation to generate the dosage needed to theoretically give a cancer patient their entire course of radiotherapy in one rapid treatment. It’s known as FLASH radiotherapy, and it’s an experimental paradigm that could represent a sea change for the world of oncology in the future. In this study, researchers also found FLASH demonstrated the same effect on tumors as traditional photon radiation while sparing healthy tissue due to the shorter exposure time. “This is the first time anyone has published findings that demonstrate the feasibility of using protons – rather than electrons – to generate FLASH doses, with an accelerator currently used for clinical treatments,” said the study’s co-senior author James M. Metz, MD, director of the Roberts Proton Therapy Center and chair of Radiation Oncology. The co-senior authors on the study are Constantinos Koumenis, PhD, the Richard H. Chamberlain Professor of Research Oncology, and Keith A. Cengel, MD, PhD, an associate professor of Radiation Oncology, both in Penn’s Perelman School of Medicine. Metz noted that other research teams have generated similar doses using electrons, which do not penetrate deep enough into the body to be clinically useful as a cancer treatment for internal tumors. Other groups have tried the approach with conventional photons, but currently available treatment devices do not have the ability to generate the necessary dosage.  This study shows, that with technical modifications, the currently available accelerators for protons can achieve FLASH doses with the biologic effects today.  The key for the Penn team was the ability to generate the dose with protons, and even in that setting, researchers had to specially develop the tools needed to effectively and accurately measure radiation doses, since the standard detectors were quickly saturated due to the high levels of radiation. The Roberts Proton Therapy Center includes a dedicated research room to run experiments like these, allowing investigators to use photon and proton radiation side-by-side just feet from the clinic. It’s one of the few facilities in the world with those unique features, and Metz said this infrastructure is what made Penn’s FLASH experiments possible. “We’ve been able to develop specialized systems in the research room to generate FLASH doses, demonstrate that we can control the proton beam, and perform a large number of experiments to help us understand the implications of FLASH radiation that we simply could not have done with a more traditional research setup,” Metz said. Researchers said they are already beginning to optimize how they would use this down the road for clinical trials, including taking the necessary steps to translate the ability from the research room to a clinical space, as well as designing a delivery system for FLASH in humans. The study’s co-lead authors are Eric S. Diffenderfer, Ioannis Verginadis, and Michele Kim. Additional Penn authors include Khayrullo Shoniyozov, Anastasia Velalopoulou, Denisa Goia, Mary Putt, Sarah Hagan, Stephen Avery, Kevin Teo, Wei Zou, Alexander Lin, Samuel Swisher-McClure, Cameron Koch, Ann R. Kennedy, Andy Minn, Amit Maity, Theresa M. Busch, and Lei Dong.
Credit: UTSW A re-analysis of clinical tests from three major U.S. laboratories showed whole exome sequencing routinely failed to adequately analyze large segments of DNA. UT Southwestern experts who conducted the review say the findings are indicative of a widespread issue for clinical laboratories. Highlights: Reanalysis of patient samples from 3 U.S. labs shows most tests didn’t adequately analyze more than a quarter of genes. Chance of detecting a disorder varied widely depending on which genes the lab completely analyzed in a given sample. Newswise — DALLAS – Jan. 6, 2020 – Children who undergo expansive genetic sequencing may not be getting the thorough DNA analysis their parents were expecting, say experts at UT Southwestern Medical Center. A review of clinical tests from three major U.S. laboratories shows whole exome sequencing routinely fails to adequately analyze large segments of DNA, a potentially critical deficiency that can prevent doctors from accurately diagnosing potential genetic disorders, from epilepsy to cancer. The reanalysis by UT Southwestern shows each lab on average adequately examined less than three-quarters of the genes – 34, 66, and 69 percent coverage – and had startlingly wide gaps in their ability to detect specific disorders. Researchers say they conducted the study because they believe vast differences in testing quality are endemic in clinical genetic sequencing but have not been well documented or shared with clinicians. “Many of the physicians who order these tests don’t know this is happening,” says Jason Park, M.D., Ph.D., associate professor of pathology at UT Southwestern. “Many of their patients are young kids with neurological disorders, and they want to get the most complete diagnostic test. But they don’t realize whole exome sequencing may miss something that a more targeted genetic test would find.” Whole exome sequencing, a technique for analyzing protein-producing genes, is increasingly used in health care to identify genetic mutations that cause disease – mostly in children but also in adults with rare or undiagnosed diseases. However, Park says the process of fully analyzing the approximately 18,000 genes in an exome is inherently difficult and prone to oversights. About half the tests do not pinpoint a mutation. The new study published in Clinical Chemistry gives insight into why some analyses may be coming back negative. Researchers re-analyzed 36 patients’ exome tests conducted between 2012 and 2016 – 12 from each of the three national clinical laboratories – and found starkly contrasting results and inconsistency with which genes were completely analyzed. A gene was not considered completely analyzed unless the lab met an industry-accepted threshold for adequate analysis of all DNA that encodes protein, which is defined as sequencing that segment at least 20 times per test. Notably, less than 1.5 percent of the genes were completely analyzed in all 36 samples. A review of one lab’s tests showed 28 percent of the genes were never adequately examined and only 5 percent were always covered. Another lab consistently covered 27 percent of the genes. “And things really start to fall apart when you start thinking about using these tests to rule out a disease,” Park says. “A negative exome result is meaningless when so many of the genes are not thoroughly analyzed.” For example, the chances of detecting an epileptic disorder from any of the 36 tests varied widely depending on which genes were analyzed. One lab conducted several patient tests that fully examined more than three quarters of the genes associated with epilepsy, but the same lab had three other patient samples in which less than 40 percent were completely analyzed. Three tests from another lab came in at under 20 percent.  “When we saw this data we made it a regular practice to ask the labs about coverage of specific genes,” says Garrett Gotway, M.D., Ph.D., a clinical geneticist at UT Southwestern who is the corresponding author of the study. “I don’t think you can expect complete coverage of 18,000 genes every time, but it’s fair to expect 90 percent or more.” The findings build upon previous research that showed similar gaps and disparities in whole genome sequencing, a technique that examines all types of genes, regardless of whether they produce proteins. Gotway says he hopes the findings will prompt more physicians to ask labs about which genes were covered and push for improved consistency in testing quality. He also encourages physicians – even before ordering the test – to consider whether whole exome sequencing is the best approach for the patient. “Clinical exomes can be helpful in complex cases, but you probably don’t need one if a kid has epilepsy and doesn’t have other complicating clinical problems,” Gotway says. “There’s a decent chance the exome test will come back negative and the parents are still left wondering about the genetic basis for their child’s disease.” In those cases, Gotway suggests ordering a smaller genetic test that completely analyzes a panel of genes associated with that disease. He says they’re less expensive and just as likely to help physicians find answers. About the study Park is medical director of the Advanced Diagnostics Laboratory at Children’s Medical Center Dallas. Gotway is assistant professor of pediatrics and internal medicine. Both are members of UT Southwestern’s Eugene McDermott Center for Human Growth and Development. About UT Southwestern Medical Center UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.
Newswise — Nurses with specialty certification may play an integral part in speeding translation of the latest research into everyday clinical practice, thereby ensuring that critically ill patients receive the highest quality of care, according to a study conducted at UPMC (University of Pittsburgh Medical Center). A survey of 268 critical care nurses in six UPMC hospitals found a strong association between nurses who were certified in critical care and their knowledge of and perceived value in specific evidence-based practices used to care for patients receiving mechanical ventilation. The results, “Factors Associated with Nurses’ Knowledge of and Perceived Value in Evidence-Based Practices,” are published in the January issue of American Journal of Critical Care (AJCC). Overall, respondents reported a high level of perceived knowledge of three specific evidence-based practices used in caring for patients receiving mechanical ventilation: spontaneous breathing trials, lung-protective ventilation and daily interruption of sedation. When compared with noncertified nurses, certified nurses reported greater perceived value of all three practices and significantly more perceived knowledge of spontaneous breathing trials and lung-protective ventilation. In addition, all respondents reported strong professional identity, self-efficacy and role clarity, all with mean scores greater than 4.0 on a 5-point scale. Nurses who held specialty certification reported higher levels of self-efficacy and role clarity than their noncertified colleagues. An interdisciplinary research team with the Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center at the University of Pittsburgh’s Department of Critical Care Medicine conducted the study in 12 adult intensive care units (ICUs) within six UPMC hospitals. The 44-item survey was associated with a larger study examining ICU team function and the delivery of evidence-based practices, with funding from the U.S. National Institutes of Health and its National Heart, Lung, and Blood Institute. “Many evidence-based practices remain underused, partly because of gaps between providers’ attitudes toward practices and the delivery of care at the bedside. Our findings support the value of nurses with specialty certification, especially among institutions that aim to improve outcomes and increase the adoption of evidence-based practices,” said co-author Kristin Hittle Gigli, PhD, RN, CPNP-AC, CCRN, a postdoctoral research fellow at the CRISMA Center.    The results did not indicate a strong relationship between nurses’ education levels and evidence-based practices, and the researchers point to the high percentage of respondents with a bachelor’s degree or higher (70.9%) as a potential factor in the lack of association. In addition, the survey did not ask about years of experience or certifications other than CCRN, which may be additional elements influencing nurses’ individual beliefs and perceptions. CCRN® specialty certification is for nurses who provide direct care to acutely/critically ill adult, pediatric or neonatal patients regardless of their physical location. Nurses interested in this certification may work in areas such as intensive care units, cardiac care units, combined ICU/CCUs, medical/surgical ICUs, trauma units or critical care transport/flight. CCRN is one of several credentials granted by AACN Certification Corporation, the credentialing arm of the American Association of Critical-Care Nurses. Currently, more than 120,000 acute and critical care nurses hold AACN Certification Corporation credentials: CCRN, CCRN-K, CCRN-E, PCCN, PCCN-K, ACNPC, ACNPC-AG, CCNS, ACCNS-AG, ACCNS-P, ACCNS-N, CMC and CSC. For more information, visit https://www.aacn.org/certification. To access the article and full-text PDF, visit the AJCC website at www.ajcconline.org.
A rendering of amyloid protein plaques accumulating between neurons in the brain. Credit: National Institute of Aging   Newswise — Writing in the December 30, 2019 online issue of Neurology, researchers at University of California San Diego School of Medicine and Veterans Affairs San Diego Healthcare System report that accumulating amyloid — an abnormal protein linked to neurodegenerative conditions such as Alzheimer’s disease (AD) — occurred faster among persons deemed to have “objectively-defined subtle cognitive difficulties” (Obj-SCD) than among persons considered to be “cognitively normal.” Classification of Obj-SCD, which has been previously shown to predict progression to mild cognitive impairment (MCI) and dementia, is determined using non-invasive but sensitive neuropsychological measures, including measures of how efficiently someone learns and retains new information or makes certain types of errors. The new findings, say authors, suggest that Obj-SCD can be detected during the preclinical state of AD when amyloid plaques are accumulating in the brain, neurodegeneration is just starting, but symptoms of impairment on total scores on thinking and memory tests have not yet been recorded. “The scientific community has long thought that amyloid drives the neurodegeneration and cognitive impairment associated with Alzheimer’s disease,” said senior author Mark W. Bondi, PhD, professor of psychiatry at UC San Diego School of Medicine and the VA San Diego Healthcare System. “These findings, in addition to other work in our lab, suggest that this is likely not the case for everyone and that sensitive neuropsychological measurement strategies capture subtle cognitive changes much earlier in the disease process than previously thought possible. “This work, led by Dr. Kelsey Thomas, has important implications for research on treatment targets for AD, as it suggests that cognitive changes may be occurring before significant levels of amyloid have accumulated. It seems like we may need to focus on treatment targets of pathologies other than amyloid, such as tau, that are more highly associated with the thinking and memory difficulties that impact people’s lives.” Study participants were enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), an on-going effort (launched in 2003) to test whether regular, repeated brain imaging, combined with other biological markers and clinical assessments, can measure the progression of MCI and early AD.  Seven hundred and forty-seven persons were involved in this study: 305 deemed cognitively normal, 153 with Obj-SCD and 289 MCI. All underwent neuropsychological testing and both PET and MRI scans. The research team found that amyloid accumulation was faster in persons classified with Obj-SCD than in the cognitively normal group. Those classified as Obj-SCD also experienced selective thinning of the entorhinal cortex, a region of the brain impacted very early in Alzheimer’s disease and associated with memory, navigation and perception of time. Persons with MCI had more amyloid in their brain at the start of the study, but they did not have faster accumulation of amyloid compared to those with normal cognition. However, those with MCI had more widespread temporal lobe atrophy, including the hippocampus. Broadly speaking, scientists believe that for most people, AD is likely caused by a combination of genetic, lifestyle and environmental factors. Increasing age is a primary, known risk factor. The amyloid hypothesis or amyloid cascade model posits that accumulating amyloid protein plaques in the brain kill neurons and gradually impair specific cognitive functions, such as memory, resulting in AD dementia. However, many scientists are now questioning the amyloid hypothesis given the large number of clinical trials in which drugs targeted and successfully cleared amyloid from the brain but did not impact the trajectory of cognitive decline. The ability to identify those at risk for AD before significant impairment and before or during the phase of faster amyloid accumulation would be a clinical boon, said authors, providing both a way to monitor disease progression and a window of opportunity to apply potential preventive or treatment strategies. Currently, both approaches are limited. Some risk factors for Alzheimer’s can be minimized, such as not smoking, managing vascular risk factors such as hypertension or following a healthy diet with regular exercise. There are a handful of medications approved for treating symptoms of AD, but as yet, there is no cure. “While the emergence of biomarkers of Alzheimer’s disease has revolutionized research and our understanding of how the disease progresses, many of these biomarkers continue to be highly expensive, inaccessible for clinical use or not available to those with certain medical conditions,” said first author Thomas, PhD, assistant professor of psychiatry at UC San Diego School of Medicine and research health scientist at the VA San Diego Healthcare System. “A method of identifying individuals at risk for progression to AD using neuropsychological measures has the potential to improve early detection in those who may otherwise not be eligible for more expensive or invasive screening.” Co-authors of this study include Kelsey R. Thomas, Katherine J. Bangen, Emily C. Edmonds, Christina G. Wong, Shanna Cooper, Lisa Delano-Wood, UC San Diego and VA San Diego Healthcare System; and Alexandra J. Weigand, UC San Diego, VA San Diego Healthcare System and San Diego State University/UC San Diego Joint Doctoral Program in Clinical Psychology. Funding for this study came, in part, from the National Institutes of Health (grants R01 AG049810, K24 AG026431), the Alzheimer’s Association (AARF-17-528918), the U.S. Department of Veterans Affairs Clinical Sciences Research and Development Service (1IK2CX001865), and the Alzheimer’s Disease Neuroimaging Initiative, which is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering and AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Disclosure: Mark Bondi receives royalties from Oxford University Press and serves as a consultant for Eisai, Novartis and Roche pharmaceutical companies. Full study: https://n.neurology.org/content/early/2019/12/29/WNL.0000000000008838
Surface of a multicillated cell        Credit: Andrew Holland Newswise — One of the wonders of cell biology is its symmetry. Mammalian cells have one nucleus and one cell membrane, and most humans have 23 pairs of chromosomes. Trillions of mammalian cells achieve this uniformity — but some consistently break this mold to fulfill unique functions. Now, a team of Johns Hopkins Medicine researchers have found how these outliers take shape. In experiments with genetically engineered mice, a research team has ruled out a mechanism that scientists have long believed controls the number of hairlike structures, called cilia, protruding on the outside of each mammalian cell. They concluded that control of the cilia count might rely instead on a process more commonly seen in non-mammalian species. The experiments, described Dec. 2 in Nature Cell Biology and led by Andrew Holland, Ph.D., associate professor of molecular biology and genetics at the Johns Hopkins University School of Medicine, may eventually help scientists learn more about human diseases related to cilia function, such as respiratory infections, infertility and hydrocephaly. Cilia are ancient structures that first appeared on single-celled organisms as small hairlike “fingers” that act as motors to move the cell or antennae to sense the environment. Nearly all human cells have at least one cilium that senses physical or chemical cues. However, some specialized cell types in humans, such as those lining the respiratory and reproductive tracts, have hundreds of cilia on their surface that beat in waves to move fluids through the system. “Our main question was how these multicilliated cells become so dramatically different than the rest of the cells in our body,” says Holland. “Most cells make exactly one cilium per cell, but these highly specialized cells give up on this tight numerical control and make hundreds of cilia.” In an effort to answer the question, Holland and his team took a closer look at the base of cilia, the place where the organelles attach and grow from the surface of the cell. This base is a microscopic, cylinder-shaped structure called a centriole. In single-ciliated cells, Holland says, centrioles are created before a cell divides. A cell contains two-parent centrioles that each duplicate so that both new cells gets one pair of centrioles — the oldest of these two centrioles then goes on to form the base of the cilium. However, multicilliated cells create unique structures, called deuterosomes, that act as a copy machine to enable the production of tens to hundreds of centrioles, allowing these cells to create many cilia. “Deuterosomes are only present in multicilliated cells, and scientists have long thought they are central for determining how many centrioles and cilia are formed,” says Holland. To test this, Holland and his team developed a mouse model that lacked the gene that creates deuterosomes. Then, they analyzed the tissues that carry multicilliated cells and counted their cilia. The researchers were surprised to find that the genetically engineered mice had the same number of cilia on cells as the mice with deuterosomes, ruling out the central role of deuterosomes in controlling the number of cilia. For example, the multicilliated cells lining the trachea all had 200–300 cillia per cell. The researchers also found that cells without deuterosomes could make new centrioles just as quickly as cells with them. With this surprising result in hand, the researchers engineered mouse cells that lacked both deuterosomes and parent centrioles, and then counted the number of cilia formed in multicilliated cells. “We figured that with no parent centrioles and no deuterosomes, the multicilliated cells would be unable to create the proper number of new cilia,” says Holland. Remarkably, Holland says, even the lack of parent centrioles had no effect on the final cilia number. Most cells in both normal and genetically engineered groups created between 50 and 90 cilia. “This finding changes the dogma of what we believed to be the driving force behind centriole assembly,” explains Holland. “Instead of needing a platform to grow on, centrioles can be created spontaneously.” While uncommon in mammals, the so-called de novo generation of centrioles is not new to the animal kingdom. Some species, such as the small flatworm planaria, lack parent centrioles entirely, and rely on de novo centriole generation to create the cilia they use to move. In further experiments on genetically engineered mice, Holland found that all the spontaneously created centrioles were assembled within a region of the cell rich with fibrogranular material — the protein components necessary to build a centriole. He says he suspects that proteins found in that little-understood area of the cell contain the essential elements necessary to construct centrioles and ultimately control the number of cilia that are formed. Everything else, the deuterosomes and even the parent centrioles, are “not strictly necessary,” he says. “We think that the deuterosomes function to relieve pressure on the parent centrioles from the demands of making many new centrioles, freeing up parent centrioles to fulfill other functions,” says Holland. A better understanding of mechanisms that limit cilia number in human cells could potentially advance efforts to treat cilia-related disorders, he said, by identifying targets for drugs. Other researchers involved in this study include Olivier Mercey of the Paris Sciences et Lettres Research University; Michelle Levine, Gina LoMastro, Valerie Gomez and Abhijay Kumar of the Johns Hopkins University School of Medicine; Philippe Rostaing, Nathalie Spassky and Alice Meunier of the Paris Sciences et Lettres Research University, the French National Centre for Scientific Research and INSERM; and Brian Mitchell of Northwestern University. This work was supported by the National Institute of General Medical Sciences (R01GM114119, R01GM133897, R01GM089970), the American Cancer Society (RSG-16-156-01-CCG), the Agence Nationale de la Recherche Investissements d’Avenir (ANR-10-LABX-54 MEMO LIFE, ANR-11-IDEX-0001-02 PSL), the European Research Council (647466) and the French National Research Agency (ANRJC JC-15-CE13-0005-01. The authors declare no competing interests.
Newswise — BLOOMINGTON, Ind. -- Indiana University researchers have discovered that a chemical compound found in essential oils improves the healing process in mice when it is topically applied to a skin wound -- a finding that could lead to improved treatments for skin injuries in humans. IU scientists also reported that skin tissue treated with the chemical compound, beta-carophyllene -- which is found in lavender, rosemary and ylang ylang, as well as various herbs and spices such as black pepper -- showed increased cell growth and cell migration critical to wound healing. They also observed increased gene expression of hair follicle stem cells in the treated tissue. The scientists did not find any involvement of the olfactory system in the wound healing. Their research was published Dec. 16 in the journal PLOS ONE. "This is the first finding at the chemical-compound level showing improved wound healing in addition to changes in gene expression in the skin," said Sachiko Koyama, corresponding author on the paper, who, at the time of this research, was an associate scientist at the IU School of Medicine and is currently a visiting scientist in the IU College of Arts and Sciences' Department of Biology. "The way gene expression changed also suggests not only improved wound healing but also the possibility of less scar formation and a more full recovery. "It's an example that essential oils work; however, it's not through our sense of smell." Essential oils are natural, concentrated oils extracted from plants. Their use by humans dates back to ancient Egypt, but the scented oils have experienced a resurgence in popularity in the U.S. over the past few years, with many people using them for aromatherapy. Koyama, whose original field of study is pheromones, said she wasn't interested in essential oils at first. The project started when she saw several students studying the wound healing process in mice in the Medical Sciences Program at the IU School of Medicine-Bloomington. Having previously worked in the IU College of Arts and Sciences' Department of Psychological and Brain Sciences, where scientists are working with cannabinoid receptors, Koyama knew that beta-caryophyllene activates not only olfactory receptors but also cannabinoid receptor 2 (CB2), which has anti-inflammatory impact when it is activated. "In the wound healing process, there are several stages, starting from the inflammatory phase, followed by the cell proliferation stage and the remodeling stage," she said. "I thought maybe wound healing would be accelerated if inflammation was suppressed, stimulating an earlier switch from the inflammatory stage to the next stage." This accelerated the wound healing process, she said, but the resulting change in gene expression indicates that the improved healing is not merely achieved through activation of the CB2 receptor. "It's possibly more complicated," Koyama said. "Our findings suggest the involvements of some other routes in addition to CB2. I hope to clarify the mechanisms of action in the near future." Although the study's results are promising, Koyama said she wouldn't recommend that people start treating their injuries with just any essential oils, as her research applies to a very specific chemical compound with known purity, diluted in a specific concentration. "It's not very precise to use the essential oils themselves because there are differences," she said. "Even if you say you used lavender, when the lavender was harvested, where it was harvested, how it was stored -- all of this makes a difference in the chemical composition." Koyama said further research is required to figure out how beta-carophyllene might be used to develop new treatments for skin wounds in humans. She said she hopes to better understand the mechanisms that accelerate the healing process and to find a combination of chemical compounds that could be used together to accelerate drug delivery and chemical stability, which is important for avoiding or suppressing allergic responses caused by oxidation of the chemical compounds. "We still need thorough scientific studies at the chemical-compound level and also to test the combinations of these chemical compounds," Koyama said. "For example, there are studies showing that linalool -- another compound found in lavender -- can suppress anxiety through the olfactory system. There could be the best combinations of chemical compounds at specific ratios, and we might be able to do prescriptions of aroma chemical compounds, depending on the specific treatment goals. "There are many things to test before we can start using it clinically, but our results are very promising and exciting; someday in the near future, we may be able to develop a drug and drug delivery methods using the chemical compounds found in essential oils." Additional IU authors on the paper include Anna Purk and Anthony Mescher of the IU School of Medicine; and, in the IU College of Arts and Sciences, Manpreet Kaur of the Department of Psychological and Brain Sciences, Helena A. Soini and Milos V. Novotny of the Department of Chemistry and the Institute for Pheromone Research, Keith Davis of the Department of Biology, and C. Cheng Kao of the Department of Molecular and Cellular Biochemistry. Hiroaki Matsunami of Duke University also authored the paper. This research was supported by the Office of the Vice Provost of Research at IU Bloomington through a Collaborative Research and Creative Activity Funding Award to Koyama. Purk and Kaur worked on the study as awardees of the Research Experience for Undergraduate Women scholarship from the IU Center of Excellence for Women in Technology. IU Research Indiana University's world-class researchers have driven innovation and creative initiatives that matter for nearly 200 years. From curing testicular cancer to collaborating with NASA to search for life on Mars, IU has earned its reputation as a world-class research institution. Supported by $680 million last year from our partners, IU researchers are building collaborations and uncovering new solutions that improve lives in Indiana and around the globe.
Newswise — Researchers at the Technion-Israel Institute of Technology and China’s Xidian University present, in Chemical Reviews, a comprehensive review of smart systems that provide continuous information on a subject’s health. These nature-inspired systems are based on advanced hybrid sensing, artificial intelligence, and cloud computing. Much of the review is based on the authors' research, which is led by Professor Hossam Haick and Yoav Broza of the Technion’s Wolfson Chemical Engineering Faculty, and Professor Weiwei Wu of Xidian University in China.“Wearable monitoring” is an inclusive term for innovative technologies that provide information on a person’s health, based on continuous monitoring of a series of biomarkers. The speedy development of this field is very important news, especially at a time of aging of the population, and the fact that people 60 years of age or older comprise about 13% of all humanity.However, for various reasons, diagnostic technologies are evolving in different ways, with no deliberate direction and no integration of the various data obtained from them. Such integration is a prerequisite for optimizing diagnosis, treatment, and follow-up. In the absence of such integration, and despite developments in medical diagnosis, in many cases the diagnosis is made very late. This reduces the ability of the medical system to address the problem successfully. Additionally, preventive medicine – one of the most important approaches in the world of medicine – is not advancing fast enough.Extending life, which is welcome in and of itself, shifts the center of gravity from serious, short-term illnesses caused by external factors such as infections and injuries that can be healed to long-term, chronic, and incurable illnesses that impair the quality of life over time. Today, nearly 45% of Americans suffer from chronic illnesses, and the need for continuous and integrative monitoring is especially important in this regard.This is the backdrop to the tireless efforts invested in recent years by Prof. Hossam Haick's research group. In the current report, the team’s researchers – in collaboration with Prof. Weiwei Wu, who did his postdoctoral fellowship under the guidance of Prof. Haick – present an in-depth and extensive review of innovative sensors that provide quick and cheap diagnostics with minimal invasiveness.In this review, researchers present a complex system that analyzes, using technological means that include cellular and cloud and Big Data analytics, a series of biomarkers derived from body fluids – blood, tears, breath, saliva, urine, brain and spinal fluid, and more. The overall goal of this research activity is to develop hybrid sensing systems that integrate different sensing technologies. For this, a combination of different fields of knowledge is required, including chemistry, electronics, and physics – a combination that takes place in Prof. Haick’s research group.“Until now, the most reliable diagnostic tools have been radiological diagnostics (such as X-rays, MRIs and CTs), laboratory tests (of urine, blood, etc.), and various microbiological tests, said Prof. Haick.The problem is that these are expensive methods that require experts to decipher the findings. Technological advances make it possible for us to introduce inexpensive, fast and exact automated methods that collect and analyze a wide range of data. By integrating various technological capabilities, we present a cheap, easy-to-use and effective follow-up tool that will provide practitioners with comprehensive and continuous feedback on the patient's health.One of the vital conditions for achieving this goal is the development of highly sensitive and accurate sensors. These, according to Prof. Haick, are inspired by nature.“Over billions of years, evolution developed excellent and efficient sensors, based, for example, on interaction among enzymes, receptors, and suction systems like the tongue of the hummingbird," said Prof. Haick. "Not only have we been inspired by these mechanisms, but we have created even better systems by using engineering, the Internet of Things (IoT), and cloud computing. The bottom line is a complex system that will supply the relevant medical professional with a continuous, comprehensive, and accurate diagnosis in real time, and recommendations for early and effective treatment."Prof. Hossam Haick is the head of the Laboratory for Nanomaterial-Based Devices in the Technion’s Wolfson Department of Chemical Engineering, and a member of the Russell Berrie Nanotechnlogy Institute (RBNI). The present study was carried out with support from the Horizon 2002 of the EU Framework for the VOGAS and A-Patch Consortiums. 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Newswise — A new study led by Washington University School of Medicine in St. Louis suggests there is a link between bacteria that live in the upper airway and the severity of asthma symptoms among children with mild to moderate asthma. The study raises the possibility that the airway’s microbiome could have a causal role in the severity of asthma symptoms. The research paves the way for future studies to discover whether altering the types of bacteria that live in the upper airway could help patients with asthma. The findings appear Dec. 16 in the journal Nature Communications. “There is an urgent need to develop better asthma therapies for these patients,” said senior author Avraham Beigelman, MD, an associate professor of pediatrics at Washington University. “Though our study can’t prove causation, it raises intriguing questions that we plan to pursue. If we somehow supplement such patients with what appear to be good bacteria, will they do better? We are interested in studying whether we can deliberately alter the airway microbiome to reduce the risk of worsening asthma symptoms.” In the U.S., more than 6 million children under age 18 have asthma, or about 1 in 12. It is the leading chronic pediatric disease and the No. 1 reason for missed school days, according to the Asthma and Allergy Foundation of America. The researchers found that children who experienced early warning signs that their asthma was going to flare up were more likely to have bacteria associated with disease — including Staphylococcus, Streptococcus and Moraxella bacterial groups — living in their upper airways. In contrast, airway microbes dominated by Corynebacterium and Dolosigranulum bacteria were associated with periods of good health, when asthma was well-controlled. Beigelman and his colleagues also found that children whose airway microbial communities switched from being dominated by Corynebacterium and Dolosigranulum bacteria to being dominated by Moraxella bacteria were at the highest risk of worsening asthma symptoms compared with children whose microbial communities made any other kind of shift. “Our data demonstrated a rapid change of the airway microbiome in the children who transitioned from respiratory health to disease,” said first author Yanjiao Zhou, MD, PhD, who conducted postdoctoral microbiome and bioinformatics research at Washington University before joining the faculty at the University of Connecticut. “It is also intriguing to find that the microbiome changing pattern could play an important role in asthma exacerbation. We are planning future studies to explore this possibility.” The upper airway microbiome study was conducted in conjunction with a clinical trial involving 214 children ages 5 to 11 with mild to moderate asthma. The trial — called Step Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS) — was conducted as part of AsthmaNet, a national network of medical centers conducting asthma research funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH). Washington University is an AsthmaNet site, and asthma specialist and co-author of the current microbiome study, Leonard B. Bacharier, MD, a professor of pediatrics at Washington University, led the pediatric portion of the STICS trial at Washington University. The clinical trial’s purpose was to determine whether quintupling the dose of an inhaled corticosteroid at the first signs of worsening asthma was better than keeping a low dose of the same medication. The trial found no benefit to the larger dose, and those results were published in The New England Journal of Medicine in 2018. During that trial, the researchers also collected nasal mucus samples from the children to study their upper airway microbiomes. Samples were collected at the beginning of the trial, when all of the participants had controlled asthma, as well as at the first early signs that asthma control was slipping. Based on these findings, Beigelman and Zhou said they plan to conduct studies in mice with carefully controlled airway microbiomes to see if the researchers can uncover a causal role for bacteria in asthma severity. In addition, such experiments could allow them to test different interventions that might deliberately alter the upper airway bacteria in a way that could be protective. Beigelman has a dual appointment. He also directs the Kipper Institute of Allergy and Immunology at Schneider Children’s Medical Center at Tel Aviv University in Israel.
Industry-first Express Scripts Digital Health Formulary will allow employers and health plans to manage this fast-growing segment of health care while improving access for patients.   By: Mark Bini Vice President, Innovation & Member Experience   As more people turn to digital programs to help manage serious illnesses and take better control of their health, Express Scripts is making it easier to connect consumers with the apps, devices and digital therapeutics that work best for them.   In May, we announced we were developing the first-ever formulary for digital health. Since then, we have been building this industry changing platform, establishing a four-stage formulary review and selection protocol and reviewing hundreds of submissions from digital health developers.   Now, we’ve established the first group of 15 clinically validated programs from leading digital health developers to be included in our first release starting in January 2020. We’ve set the bar high for clinical effectiveness, user experience and financial value for digital health solutions, while also combining coverage into the pharmacy benefit and providing patients with expert support from Express Scripts specialist pharmacists.   The First Cohort The Express Scripts Digital Health Formulary initially includes 15 solutions, including remote monitoring services and digital therapeutics, that aid in the management of eight of the country’s most common chronic conditions: diabetes, prediabetes, hypertension, asthma, pulmonary disease, depression, anxiety and insomnia.    These solutions engage with patients in a variety of ways, for example: allowing a pharmacist or nurse to remotely monitor a patient’s use of a drug therapy; synching with a diagnostic device that provides patients or their caregivers with vital information, like blood sugar or blood pressure, and alerts them to potential concerns; offering virtual personal coaching from a health or wellness professional; and providing virtual support from a patient’s peer.   Laying the Groundwork for the Future of Care The Express Scripts Digital Health Formulary will do for the developing digital health care industry what our drug formularies have achieved for prescription medications for more than 20 years – access, choice and value for payers and patients.   Participating health plans and employers can increase patients’ access to emerging products and technologies simply and affordably, and can rest easier with the knowledge that these new tools have been reviewed by a team of experts who will ensure the products work, provide a user-friendly experience and are worth the investment. People who use a program on the Digital Health Formulary also will receive support from Express Scripts specialist pharmacists to ensure appropriate use of the technology.   With more than 300,000 digital products on the market today, it can be overwhelming to figure out which one is best for a specific condition. Currently, employers and health plans offer digital health programs to their members without a common review process, a way to obtain the best value, or an ability to easily integrate the product into their overall health benefit. Research from the National Business Group on Health shows that half of employers anticipate digital health solutions having a very significant impact on their members. However, the digital health industry itself is still relatively new: a quarter of digital health companies have less than two years of experience.   Access + Clinical Support Digital health care is creating a sea change for pharmacists, allowing them to expand their roles to counsel patients on how they can use a digital health product or program to achieve their health goals.   For example, in just one year, pulmonary remote monitoring with the Propeller Health program – in concert with Express Scripts pulmonary specialist pharmacist support – led to improvements in symptoms, an 82% decrease in use of rescue inhalers, and a 10% increase in adherence to controller medications that help to prevent adverse asthma symptoms and exacerbations.   It’s our job to find the right digital health solutions for our clients and patients, and then make sure patients use these solutions effectively. With the Express Scripts Digital Health Formulary, we’ve created more than just a list of approved programs or a vendor management process. We built a foundation for the future of care and pharmacy that will deliver better access, affordability and health.
Newswise — Intermittent fasting may provide significant health benefits, including improved cardiometabolic health, improved blood chemistry and reduced risk for diabetes, new research conducted in part at Texas State University indicates.  Matthew McAllister, assistant professor in the Department of Health and Human Performance, co-authored the study with Liliana Renteria, graduate research assistant in the Department of Health and Human Performance, along with Brandon Pigg and Hunter Waldman of the Department of Kinesiology at Mississippi State University. Their research, "Time-restricted feeding improves markers of Cardiometabolic health in physically active college-age men: A 4-week randomized pre-post pilot study," is published in the journal Nutrition Research (https://doi.org/10.1016/j.nutres.2019.12.001). "What we are doing is time-restricted feeding. It is a way to use fasting each day to promote various aspects of cardiometabolic health," McAllister said.  Time-restricted feeding (TRF) has been shown to improve body composition and blood lipids, as well as reduce markers of inflammation and oxidative stress. However, those results originated from rodent models and studies with small human samples. In the Texas State study, 22 men were divided into two groups to complete a 28-day study. Subjects ate daily during one eight-hour period, for example, between 9 a.m. and 5 p.m. or between noon and 8 p.m. For 16 hours of the day, they did not eat or drink anything other than water.  While both groups underwent TRF, one group's caloric intake was controlled during meal periods to ensure they ate the same amount as before the study, while members of the other group were allowed to eat as much as they wanted.  "My initial thought was that if you are going to restrict the time, you would eat fewer calories. And the reduction of daily calories would cause weight loss and other health benefits," McAllister said. "But these benefits are found with no change in caloric intake—things like loss in body fat, reduced blood pressure, reduced inflammation.” Fasting blood samples were analyzed for glucose and lipids, as well as adiponectin, human growth hormone, insulin, cortisol, c-reactive protein, superoxide dismutase, total nitrate/nitrite and glutathione. Results showed that both groups experienced significant reductions in body fat, blood pressure and significant increases in adiponectin and HDL-c. No change in caloric intake was detected among members of either group.