News

Newswise — Microglia -- the brain's immune cells -- play a primary role in removing cellular debris from the brain. According to a recent study by a Nagoya University-led research team in Japan, another kind of brain cell, called astrocyte, is also involved in removing debris as a backup to microglia. The finding, published recently in The EMBO Journal, could lead to new therapies that accelerate the removal of cellular debris from the brain and thereby reduce detrimental effects of the debris on surrounding cells. Even in a healthy brain, neurons die at a certain rate, which increases with age. As dead cells and cellular debris accumulate, they harm surrounding cells, which in turn accelerates neuron death and causes neurodegenerative diseases such as Alzheimer's disease. Microglia -- brain "phagocytes" (a type of cell that engulfs and absorbs bacteria and cellular debris) -- act to clear the danger, but the debris sometimes overwhelms the microglia. This has led to suggestions that another mechanism that helps remove cellular debris is also at work. To clarify the nature of the alternative debris-clearing mechanism, a research team led by Dr. Hiroshi Kiyama and Dr. Hiroyuki Konishi of the Graduate School of Medicine at Nagoya University first investigated what would happen to microglial debris in the brains of mouse models in which microglial death was induced. As expected, the team observed that dead microglia were cleared, indicating that indeed another phagocyte was at work. The researchers next analyzed the expression of molecules in the brains of the mouse models and identified astrocytes that play a role in the removal of microglial debris. Then, using mutant mice with phagocytosis-impaired microglia, they examined how astrocytes work when microglia don't function properly. The results showed that almost half of the cellular debris was engulfed by astrocytes, not by microglia. This indicates that astrocytes have the potential to compensate for microglial dysfunction. The team concluded that not only are astrocytes capable of engulfing cellular debris, but also that they are likely to actually do this when microglia don't function properly. The team next plans to clarify how astrocytes recognize microglial dysfunction and deploy their phagocytic function. Drs. Kiyama and Konishi say, "Further investigation of how to control astrocytic phagocytosis may lead to new therapies that accelerate efficient debris clearance from aged or injured brains."   Photo credit: Hiroyuki Konishi Microglial ablation or microglial dysfunction actuates phagocytic activity of astrocytes. Astrocytes possess phagocytic machinery and have the potential to compensate for microglia with dysfunctional phagocytic activity.

Newswise — COVID-19 has significantly increased public use of face masks to protect others from the wearer’s respiratory droplets as well as the wearer from airborne contaminants. After each wear however, bacteria from even a healthy wearer’s own respiratory droplets collect on the inside of a mask as well as the outside, which could contain airborne pathogens capable of living on its surface. Although proper sanitization is imperative, many people reuse masks and other face coverings many times without sanitizing them. That is likely because current sanitization methods can be cumbersome. To address the many pitfalls of sanitizing all types of face masks from N-95s to cloth and surgical masks, a scientist from Florida Atlantic University’s Schmidt College of Medicine has come up with an innovative solution. Patrick Grant, Ph.D., associate professor of biomedical science, has designed a compact and portable sanitizing device for masks and other items that can be used at home or at work. The “portable hanging rack device” has been designed as an enclosed chamber that comes in two forms – a plastic container with a handle and a stainless steel compartment. The hanging rack and an ultraviolet-C (UV-C) light source is placed within either of these enclosed chambers and is capable of sterilizing up to six masks simultaneously and quickly, killing bacteria, yeasts, mold spores, and viruses. The masks are positioned vertically on the internal rack. To prevent the UV light from harming a user’s skin and eyes, the light source is shielded within the housing enclosure. When UV-C radiation contacts the mask, the surface of the mask is subsequently sanitized as the radiation deactivates the biological components of pathogens. The UV-C light source delivers uninterrupted UV-C radiation to the mask surfaces and uses a UV-C bulb that produces limited ozone. Grant has tested a number of micro-organisms using this device and has shown its efficacy against pathogens including the highly-contagious E-coli, which was eradicated within the device in about one minute. FAU recently filed a provisional patent application for Grant’s novel invention with the United States Patent & Trademark Office.    “People only have access to a limited supply of masks and often don’t have the option of disposing of them after a single use,” said Grant. “Those who wear cloth masks may sanitize them by washing them, but the washing and drying process is often too time-consuming to sustain washing after each wear. Moreover, washing is not an option for those who wear medical-grade masks, and using disinfectant sprays can cause skin irritation or damage the fibers of the mask designed to catch particulates. That’s why I created this device as a time-efficient way to sanitize facial coverings without damaging their effectiveness and enable wearers to safely reuse them in their daily lives.”  Although there are commercially-available UV-C treatment devices, many of the devices permitting sanitization of multiple objects are of a commercial size that is too large for household use. Furthermore, these devices frequently utilize larger UV bulbs, which are not only costly, but also produce ozone, resulting in an unpleasant odor. In addition, current portable devices are not suitably adapted to sanitize the entire surface of multiple masks at once – a concern for families using multiple face coverings on a daily basis. While handheld-UV wands exist, these wands increase exposure to UV rays and often require the user to hold the wand for a lengthy period of time to properly sanitize the desired surface, increasing the user’s risk of skin burns and damage to the corneas of the eyes. Studies also have shown users of hand-held devices are unable to hold the devices at the angle and for the length of time necessary to generate a stable UV directional output and effectively sanitize a surface. Moreover, open-air UV devices risk UV exposure to commonly found household surfaces such as plastics, which may damage the integrity and appearance of these materials. When fully developed, this apparatus will effectively sanitize masks as well as other objects such as keys and smart phones in a way that is safe, affordable, odor-free, and suitable for household use. Grant anticipates the cost of the plastic portable container and the steel container to be under $100 and to provide cost savings from an extended life of masks and from potential savings from reducing preventable infections.   Photo Credit: Patrick Grant, Ph.D., Florida Atlantic University Video shows two versions of the “portable hanging rack device” and the researcher swabbing a face mask and placing it onto a Petri dish. The cover image is a side-by-side view of bacteria from a face mask before and after using the sanitization device. When UV-C radiation contacts the mask, the surface of the mask is subsequently sanitized as the radiation deactivates the biological components of pathogens.

Newswise — ARLINGTON, Va., October 21, 2020 — A new clinical guideline from the American Society for Radiation Oncology (ASTRO) provides guidance for physicians who use radiation therapy to treat patients with locally advanced rectal cancer. Recommendations outline indications and best practices for pelvic radiation treatments, as well as the integration of radiation with chemotherapy and surgery for stage II-III disease. The guideline, which replaces ASTRO's 2016 guidance for rectal cancer, is published in Practical Radiation Oncology. Colorectal cancer is the second most common cause of cancer death in the U.S., and half of new colorectal cancer diagnoses are in people age 66 or younger. Rectal cancer diagnoses account for nearly one-third of colorectal cancers; an estimated 43,340 adults will be diagnosed with rectal cancer in 2020. While rectal cancer incidence and mortality rates have dropped among older adults in recent years, they have increased for those younger than age 55. "As rectal cancer becomes more of a disease of younger adults, long-term survivorship and quality of life considerations become even more important. Part of our motivation was to create guidelines that provide options for different treatments that could potentially improve survival rates and also help preserve patients' quality of life," said Prajnan Das, MD, MPH, chair of the rectal guideline task force, and professor and chief of gastrointestinal radiation oncology at The University of Texas MD Anderson Cancer Center in Houston. Standard treatment for locally advanced rectal cancer generally involves chemoradiation therapy or short-course radiation without chemotherapy, followed by tumor removal surgery and additional chemotherapy. More recently, several trials have shown potential for emerging paradigms, such as changing the sequencing of treatments or omitting portions of treatments for select patients. "Different treatments are appropriate for different patients, and the oncology field at large is moving toward personalized care," explained Jennifer Y. Wo, MD, vice chair of the rectal guideline task force and associate professor of radiation oncology at Harvard Medical School and Massachusetts General Hospital in Boston. "Some patients may need less than what is considered a typical course of treatment, while some patients may need more. This guideline focuses on providing options that can be tailored to patients' characteristics and their wishes." Recommendations in the guideline address patient selection for radiation therapy, delivery of pelvic radiation treatments, options for non-operative management of locally advanced rectal cancer and guidance for follow-up care. Key recommendations include: Neoadjuvant radiation therapy is strongly recommended for patients with clinical stage II-III rectal cancer to reduce their risk of locoregional recurrence. Radiation therapy for locally advanced rectal cancer should be performed before rather than after surgery. Radiation may be omitted in favor of upfront surgery for some patients at low risk of recurrence, after discussion by a multidisciplinary care team. Clinical staging involving a physical exam and pelvic MRI is critical to determine which patients should receive neoadjuvant radiation therapy. For patients who require neoadjuvant radiation therapy, both conventionally fractionated radiation and short-course radiation are recommended equally, given high-quality evidence for similar efficacy and patient-reported quality of life outcomes with each treatment. The guideline specifies optimal dosing, fractionation and delivery techniques for radiation therapy Recommendations address how to incorporate chemotherapy into the pre-operative setting for patients who are at high risk of recurrence and who would likely benefit from the additional treatment using a total neoadjuvant therapy (TNT) approach. Recommendations also address other sequencing and timing issues for radiation, chemotherapy and surgery, with specific attention to treatment tolerability and potential downstaging. Organ preservation approaches (i.e., non-operative management and local excision) may present an alternative to radical surgery for select patients, especially those who would have a permanent colostomy or inadequate bowel continence after surgery. The guideline outlines specific criteria for situations where surgery can be avoided, as well as long-term surveillance and care for these patients. COVID-19 and Rectal Cancer While the guideline was completed before the COVID-19 pandemic, recommendations can guide clinics as they continue to care for patients. To reduce how frequently patients needed to come into the clinic for treatment, many institutions across the country moved toward short-course radiation in the early months of the pandemic, which aligns with the guideline's recommendations. "Patients usually complete short-course radiation therapy in one week, compared to five-and-a-half weeks for standard radiation treatment. That is particularly important in the COVID era, when you want to minimize patient time in the hospital and issues like financial toxicity are especially salient," said Dr. Das. "We have yet to see the true impact of COVID-19, but we know that interruptions in screening likely will lead to fewer patients receiving treatment when their disease is more manageable," said Dr. Wo. "And if that does happen and we start seeing patients with more advanced disease, then the parts of the guidelines that specifically address treatment for high-risk patients will become even more important." About the Guideline The guideline was based on a systematic literature review of articles published from January 1999 through April 2019. The multidisciplinary task force included radiation, medical and surgical oncologists, a radiation oncology resident, medical physicists and a patient representative. The guideline was developed in collaboration with the American Society of Clinical Oncology and the Society of Surgical Oncology, and endorsed by the American College of Radiology, Canadian Association of Radiation Oncology, European Society for Radiotherapy and Oncology, the Royal Australian and New Zealand College of Radiologists and the Society of Surgical Oncology. ASTRO's clinical guidelines are intended as tools to promote appropriately individualized, shared decision-making between physicians and patients. None should be construed as strict or superseding the appropriately informed and considered judgments of individual physicians and patients. Additional Resources on Colorectal Cancers Video: Radiation Therapy for Colon, Rectum and Anus Cancers; An Introduction to Radiation Therapy (Spanish) Brochure: Radiation Therapy for Colon, Rectum and Anus Cancers Chart: Side Effects of Colorectal Cancer Radiation Treatment ABOUT ASTRO The American Society for Radiation Oncology (ASTRO) is the world’s largest radiation oncology society, with more than 10,000 members who are physicians, nurses, biologists, physicists, radiation therapists, dosimetrists and other health care professionals who specialize in treating patients with radiation therapies. The Society is dedicated to improving patient care through professional education and training, support for clinical practice and health policy standards, advancement of science and research, and advocacy. ASTRO publishes three medical journals, International Journal of Radiation Oncology • Biology • Physics, Practical Radiation Oncology and Advances in Radiation Oncology; developed and maintains an extensive patient website, RT Answers; and created the nonprofit foundation Radiation Oncology Institute. To learn more about ASTRO, visit our website, sign up to receive our news and follow us on our blog, Facebook, Twitter and LinkedIn.

Newswise — Rutgers researchers have discovered human gene markers that work together to cause metastatic prostate cancer – cancer that spreads beyond the prostate. The study, published in the journal Nature Cancer, explored prostate cancer cells from people and mice and found a wide collaboration among 16 genes that leads to metastasis, which often leads to treatment challenges. The gene markers identified can predict if a prostate cancer patient has a high probability of developing metastasis, including bone. Prostate cancer is the second leading cause of cancer-related deaths among men in the United States with a five-year relative survival rate of near 100 percent when diagnosed early. Metastatic prostate cancer has a five-year survival rate of 30 percent. Current therapeutics like first- and next- generation anti-androgens that target male sex hormones alongside radiation, chemotherapy and others are not always effective, and it’s impossible to predict which patients are at risk of developing the advanced late stage of the disease. “People diagnosed with prostate cancer should now be screened for the protein markers discovered to help determine their risk of developing metastatic prostate cancer, which can help inform more personalized therapy,” said Antonina Mitrofanova, an assistant professor at the Rutgers School of Health Professions and research member at Rutgers Cancer Institute of New Jersey. “Our results show that molecular profiling at the time of diagnosis can help inform more personalized therapy leading to better outcomes for those with this advanced form of disease.” Researchers say testing for these gene markers can also predict which patients will fail to respond to normally used androgen targeting therapies in metastatic disease and can decrease multiple treatment rounds for patients. Researchers, in collaboration with Cory Abate-Shen’s lab at Columbia University, have obtained a patent for their discovery and are looking to develop therapeutics and diagnostic tools.

Newswise — Taking into account two common kidney disease tests may greatly enhance doctors’ abilities to estimate patients’ cardiovascular disease risks, enabling millions of patients to have better preventive cardiovascular care, according to a large international study co-led by researchers at the Johns Hopkins Bloomberg School of Public Health. The researchers used data from more than nine million individuals around the world to develop and validate a risk-scoring calculation that adds blood and urine measures of kidney disease to the current standard method in the United States for assessing cardiovascular disease risk. The two measures—estimated glomerular filtration rate and urine albumin—are commonly used to reveal chronic kidney disease. CKD, as it’s called, has long been considered a risk factor for cardiovascular disease, although until now CKD-related measures have not been included in standard algorithms for quantifying cardiovascular disease risk. The researchers showed that the use of their “CKD patch”—a computer-program update—can result in large increases in cardiovascular disease-risk estimates among patients with severe CKD. The investigators also developed a similar patch to enhance the standard risk-assessment tool used in Europe. The study appears October 14 in EClinicalMedicine, a new online open-access journal published by The Lancet. “Adding these two measures of kidney disease, which are frequently available from blood and urine tests at checkups, allows potentially big improvements in the accuracy of a patient’s risk estimates—improvements that should in turn enable doctors to optimize patient care,” says study co-first author Kunihiro Matsushita, MD, an associate professor in the Bloomberg School’s Department of Epidemiology. “This is a big deal—an estimated ten percent of the United States adult population has kidney disease and potentially would benefit from improved care if this new tool is adopted,” says co-last author Josef Coresh, MD, George W. Comstock Professor in the Department of Epidemiology at the Bloomberg School. The other co-first author was Simerjot Jassal, MD, of the University of California, San Diego, and the other co-last author was Elke Schaeffner, MD, of Charité University Hospital Berlin. Shoshana Ballew, PhD, assistant scientist in the Bloomberg School’s Department of Epidemiology, helped coordinate the data-gathering. In all, the study included more than 50 researchers. The reduction of kidney function in CKD can lead to higher blood pressure as well as hormonal and other chemical imbalances, and these in turn promote the narrowing of arteries that supply the heart muscle—conditions known as atherosclerosis and arteriolosclerosis. The American Heart Association and the American College of Cardiology, in their guidelines for physicians, already list CKD as a “risk enhancer” for atherosclerotic cardiovascular disease, but without a specific tool that quantifies the added risk as part of the standard risk calculator. Since 2009, Coresh, Matsushita, and colleagues have been assembling a large, international database of CKD patients and healthy adults, under a collaboration known as the CKD Prognosis Consortium. For the new study, they analyzed a portion of this database, covering 4.1 million adults around the world, to develop algorithms that estimate cardiovascular disease risk using standard measures plus the two kidney-disease measures. They then validated the accuracy of their algorithms using further samples covering 4.9 million adults. The two kidney disease measures, estimated glomerular filtration rate and urine albumin, respectively, indicate the kidneys’ blood-filtering efficiency and the level of an essential protein called albumin that the kidneys normally would filter out of the urine. The researchers incorporated these measures in a “CKD patch” to the standard cardiovascular disease-risk estimation algorithm developed by the American Heart Association and the American College of Cardiology. They found that for adults who had results on these kidney- disease tests indicating CKD, the addition of these measures via the CKD patch significantly improved the estimated 10-year risks of atherosclerotic cardiovascular disease. For example, for patients with “very high-risk” CKD, the estimated 10-year chances of developing atherosclerotic cardiovascular disease were a median of 1.55 times higher than estimates without the CKD patch, while the figures were a median of 1.24 times higher for “high-risk” CKD patients. The researchers’ CKD patch for the standard European 10-year cardiovascular disease mortality risk estimator also boosted estimated risks, by a median of 2.64 times in very high-risk CKD patients, and 1.86 times in high-risk CKD patients. “These results suggest that doctors have tended to underestimate cardiovascular disease risks in kidney disease patients,” Matsushita says. The researchers hope that their CKD patches will be adopted widely, enabling more accurate assessments of cardiovascular disease and related mortality risks—which in turn should result in better preventive care including the use of statins and other interventions to ward off cardiovascular disease. “We also hope that the availability and value of these new algorithms will encourage doctors to order estimated glomerular filtration rate and urine albumin tests for their patients more often,” Coresh says. The CKD patches are available online at: http://ckdpcrisk.org/ckdpatchscore/ and http://www.ckdpcrisk.org/ckdpatchpce/ The study, “Incorporating kidney disease measures into cardiovascular risk prediction: Development and validation in 9 million adults from 72 datasets,” was funded by the National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases.

Newswise — Without directly invading the brain or nerves, the virus responsible for COVID-19 causes potentially damaging neurological injuries in about one in seven infected, a new study shows. These injuries range from temporary confusion due to low body-oxygen levels, to stroke and seizures in the most serious cases, say the study authors.  Led by researchers at NYU Grossman School of Medicine, the study showed no cases of brain or nerve inflammation (meningitis or encephalitis), indicating no immediate invasion of these organs by the pandemic virus, SARS-CoV-2.  While this should reassure patients, the neurological complications of COVID-19 should be taken seriously because they dramatically raise a patient’s risk of dying while still in hospital (by 38 percent), researchers say. Such adverse effects also raise a coronavirus patient’s likelihood (by 28 percent) of needing long-term or rehabilitation therapy immediately after their stay in hospital.  “The results of our study showed no signs that the coronavirus directly attacks the nervous system,” says study lead investigator Jennifer Frontera, MD. “The neurological complications seen in COVID-19 are predominately the secondary effects of being severely ill and suffering from low oxygen levels in the body for prolonged periods of time,” says Frontera, a professor in the Department of Neurology at NYU Langone Health.  Published in the journal Neurology online Oct. 5, the study closely monitored the progress of 606 COVID-19 adult patients diagnosed with brain or other nerve-related medical conditions at any of four NYU Langone hospitals in New York City and Long Island between March 10 and May 20, when coronavirus infections were at their peak in the region.  Frontera says that ahead of the pandemic, dozens of NYU Langone neurologists and trainees had deployed across its medical centers to assist with the expectant surge of COVID-19 patients.  Early reports from Asia and Europe, where infections had spiked before rising in the United States, she says, had also “raised the alarm” about possible brain damage from coronavirus infection. Because of this, the research team was ready to look for any signs of neurological dysfunction among the thousands of patients being admitted to hospital in the spring. Among all the hospitals, 4,491 patients tested positive for COVID-19 during that time.  Among the study’s other key results was that common neurological problems, such as confusion caused by chemical electrolyte imbalances, severe infection or kidney failure, usually arose within 48 hours of developing general COVID-19 symptoms, including fever, difficulty breathing, and cough.  Half of those neurologically affected were over the age of 71, which researchers say is significantly older than the other 3,885 patients with COVID-19 (at a media age of 63) who did not experience brain dysfunction. Most were men (66 percent) and white (63 percent). Frontera notes that the study results do suggest that Blacks are not at greater risk of neurological complications than other COVID-19 patients, which is “welcome news,” given that Blacks are widely known to be at greater risk of death from coronavirus infection. However, she says this potentially important observation requires further investigation. While the coronavirus is known to attack other organs, including blood vessels and the heart, researchers say its main target is the lungs, where it makes breathing difficult, starving the body of oxygen it needs to stay alive. Low levels of oxygen in the body and brain was another common neurological problem, study results showed, that could lead to confusion, coma, or permanent brain damage. “Our study results suggest that physicians need to be more aggressive in stabilizing body oxygen levels in patients with COVID-19 as a potentially key therapy for stopping, preventing and/or possibly reversing neurological problems,” says study senior investigator Steven Galetta, MD. Galetta, the Philip K. Moskowitz, MD Professor and chair of the Department of Neurology at NYU Langone, says various blood-oxygen-raising therapies that could possibly work against neurological problems in patients with COVID-19 include early intubation or use of heart-lung machines, called ECMO, which mechanically “clean” the blood and “deliver” oxygen into it. Funding support for the study was provided by National Institutes of Health grant P30 AG066512 and NYU Langone. Besides Frontera and Galetta, other NYU Langone researchers involved in this study are Sakinah Sabadia, MD; Rebecca Lalchlan, DO; Taolin Fang, MD; Brent Flusty, DO; Patricio Millar-Vernetti, MD; Thomas Snyder, MD; Stephen Berger, MD; Dixon Yang, MD; Andre Granger, MD; Nicole Morgan, MD; Palek Patel, MD; Josef Gutman, MD; Kara Melmed, MD; Shashank Agarwal, MD; Mathew Bokhari, MD; Kaitlyn Lillemoe, MD; Daniel Friedman, MD; David Friedman, MD; Manisha Holmes, MD; Joshua Huang, MSc; Sujata Thawani, MD; Jonathan Howard, MD; Nada Abou-Fayssal, MD; Penina Krieger, MPhil; Ariane Lewis, MD: Aaron Lord, MD; Ting Zhou, MD; D. Ethan Kahn, DO; Barry Czeisler, MD; Jose Torres, MD; Shadi Yaghi, MD; Koto Ishida, MD; Erica Scher, RN, MPH; Dimitris Placatonakis, MD, PhD; Mengling Liu, PhD; Thomas Wisniewski, MD; Andrea Troxel, ScD; and Laura Balcer, MD, MSCE. Other study co-investigators are Sherry Chou, MD, MSc; and Ericka Fink, MD, at the University of Pittsburgh; Molly McNett, RN; and Shraddha Mainali, MD, at Ohio State University in Columbus; Raimund Helbok, MD, PhD, at the Medical University of Innsbruck in Austria; Courtney Robinson, MD; Jose Suarez, MD; and Wendy Ziai, MD, at Johns Hopkins University in Baltimore, Md.; Michelle Schober, MD; and Adam de Havenon, MD, at the University of Utah in Salt Lake City; and David Menon, MD, PhD, at the University of Cambridge in the United Kingdom.

Newswise — PITTSBURGH, Oct. 12, 2020 – Variations in a gene that regulates dopamine levels in the brain may influence the mobility of elderly and frail adults, according to new research from the University of Pittsburgh Graduate School of Public Health.  These results, published today in the Journal of The American Geriatrics Society, add to a growing body of evidence hinting that lower dopamine levels could contribute to the slower, often disabling walking patterns seen in some elderly populations.  “Most people think about dopamine’s role in mobility in the context of Parkinson’s disease, but not in normal aging,” said senior author Caterina Rosano, M.D., M.P.H., professor of epidemiology at Pitt Public Health. “We were curious to see if a genetic predisposition to produce more or less dopamine was related to mobility in individuals who had some level of frailty, yet did not have dementia, parkinsonism or any other neurological condition.”  While several genetic elements control dopamine signaling, Rosano and her team focused on a gene called COMT, which breaks down dopamine to control its levels within the brain. They also considered the frailty status of participants, which is a common consequence of aging marked by a decline in physiological function, poor adjustment to stressors and a susceptibility toward adverse health outcomes. The researchers suspected that frail participants could be particularly vulnerable to COMT-driven differences in dopamine levels.  Rosano and her collaborators examined this gene in more than 500 adults above the age of 65 in Pennsylvania, North Carolina, California and Maryland, excluding any participants taking dopamine-related medications or diagnosed with Parkinson’s disease. The researchers then looked for potential links between genotype, frailty and speed.  “We found that in older, frail adults, those who have a high-dopamine genotype are more likely to maintain a faster gait and may be more resilient to mobility disablement as they age,” said Rosano.  The team discovered that frail participants with a high-dopamine COMT genotype had a 10% faster walking speed compared with participants with the low-dopamine COMT genotype.  “This 10% difference may seem small, but it could make a big difference for a person walking across a busy street while negotiating traffic,” said Rosano. “This difference is even more striking when you consider just how many complex genes influence walking.”  Rosano and study co-author Nicolaas Bohnen, M.D., Ph.D., professor of neurology and radiology at the University of Michigan School of Medicine, are working with a team of scientists at Pitt to quantify what level of dopamine could give elders greater resilience to gait-slowing and mobility disablement. Their hope is that older adults with low dopamine levels could one day receive pharmacologic supplements of dopamine to help preserve their mobility.  “There are a lot of individuals living in the community who have dopamine levels toward the lower end of normal who don't have Parkinson's disease or psychiatric conditions,” said Rosano. “If we give dopamine to these people, could we make them more resilient? That's what we don't know yet.”  In the meantime, she suggests that there are actions that seniors can take today to keep moving. She recommends that elders focus on physical activities that are enjoyable and involve both the body and the brain, especially multi-sensory activities, such as dancing or walking with a loved one.  “I love to see grandparents walking around holding hands with their grandchildren because they have to look where they are going, where the child is going, keep an eye on the surroundings and pay attention to what the grandchild is saying, all at the same time,” said Rosano. “They get an amazing multi-sensory rehab, and it's fantastic.”  Additional authors on this research include first author Shannon Mance, B.S.N., R.N., Andrea Rosso, M.P.H., Ph.D., and Stephanie Studenski, M.D., M.P.H., all of Pitt; and Joshua Bis, Ph.D., of the University of Washington.  This research was supported by the National Institutes of Health (NIH) contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086 and NIH grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, U01HL130114, R01AG023629, and DK063491. Additional support was provided by UCLA Clinical Translational Science Institute grant UL1TR00181.    CREDIT: Ric Evans/Pitt CAPTION: Caterina Rosano, M.D., M.P.H., professor of epidemiology, University of Pittsburgh Graduate School of Public Health.

Newswise — Rockville, Md. (October 6, 2020)—Researchers have used “omics” data containing genetic profiles of drugs to identify the hormone oxytocin as a possible treatment for COVID-19, the disease caused by the novel coronavirus (SARS-CoV-2). The study is published in Physiological Genomics. It was chosen as an APSselect article for October. Increased inflammation that leads to a “cytokine storm”—in which the body attacks its own tissues—remains one of the most serious and least understood complications of COVID-19. To date, there are no medications approved by the U.S. Food and Drug Administration to treat COVID-19, which means that “repurposing existing drugs that can act on the adaptive immune response and prevent the cytokine storm in early phases of the disease is a priority,” authors of a new study wrote. Oxytocin, a hormone produced in the brain, is involved in reproduction and childbirth. A synthetic form of oxytocin, frequently known by its brand name Pitocin, is given by an IV to some people to help labor progress and to stop bleeding after childbirth. Oxytocin also has anti-inflammatory properties, which promote an immune response. Previous research suggests the hormone protects against toxic injury and reduces levels of inflammatory substances in the lungs. Studies have also shown that cultured human cells with reduced expression of oxytocin receptors have higher levels of inflammatory proteins and oxidative stress. The researchers of the new study used the National Institutes of Health’s Library of Integrated Network-Based Cellular Signatures database to analyze characteristics of genes that have been treated with drugs closely related to oxytocin. They found one drug in particular, carbetocin, has similar characteristics (called a signature) to genes with reduced expression of the inflammatory markers that trigger cytokine storm in people with COVID-19. Carbetocin’s signature indicates that the drug may promote the activation of T cells, which are immune cells that play an important role in immune response. Carbetocin’s signature is also similar to that of lopinavir, an antiretroviral medication already being explored as a treatment for COVID-19. All of these factors point to the promising potential of oxytocin as a targeted treatment for coronavirus-related cytokine storms. “Understanding the mechanisms by which [oxytocin] or the [oxytocin system] can be a new immune target is crucial,” the research team wrote. However, “safety and efficacy of intravenous oxytocin in hospitalized patients with COVID-19 remains to be assessed.” Read the full article, “Oxytocin’s anti-inflammatory and proimmune functions in COVID-19: a transcriptomic signature-based approach,” published in Physiological Genomics. It is highlighted as one of this month’s “best of the best” as part of the American Physiological Society’s APSselect program. Read all of this month’s selected research articles. NOTE TO JOURNALISTS: To schedule an interview with a member of the research team, please contact the APS Communications Office or call 301.634.7314. Find more research highlights in our Newsroom. Physiology is a broad area of scientific inquiry that focuses on how molecules, cells, tissues and organs function in health and disease. The American Physiological Society connects a global, multidisciplinary community of more than 10,000 biomedical scientists and educators as part of its mission to advance scientific discovery, understand life and improve health. The Society drives collaboration and spotlights scientific discoveries through its 16 scholarly journals and programming that support researchers and educators in their work.

UCLA Fielding School of Public Health faculty co-led study that found at least 10 distinct “hotspot” mutations in more than 80% of samples of the viruses’ genomes   Newswise — LOS ANGELES (Sept. 29, 2020) – Researchers have found at least 10 distinct “hotspot” mutations in more than 80% of randomly selected SAR-CoV-2 sequences from six countries, and these genome hotspots – seen as "typos" that can occur as the virus replicates during cellular division – could have a significant impact in the fight against the COVID-19 pandemic. “These hotspots might select for more pathogenic variants,” said Christina Ramirez, UCLA Fielding School of Public Health professor of biostatistics, a co-author of the study. “Alternatively, mutations might evolve and could prove to be less pathogenic – the virus, after all, only survives when the host survives.” The speed at which novel SARS-CoV-2 mutants are selected and dispersed around the world may also pose issues for the development of vaccines and therapeutics, according to the study in the journal Virus Research, co-authored by Ramirez and colleagues Stefanie Weber and Walter Doerfler, both of the Institute for Clinical and Molecular Virology, Friedrich-Alexander University (FAU), Erlangen, Germany. “One of the major scientific problems confronted with by the SARS-CoV-2 pandemic lies in our limited understanding of the interactions between the viral and the human host genomes and the latter’s defense mechanisms against this pathogen,” said Doerfler, a physician and molecular geneticist.  “The results of our study will provide a platform for those who take care of patients with infections.” RESEARCH BRIEF FINDINGS During worldwide spreading among human populations, at least 10 distinct hotspot mutations had been selected and found in up to more than 80% of the randomly selected sequences from 6 countries. The increasing frequency of SARS-CoV-2 mutation hotspots might select for dangerous viral pathogens. Alternatively, there might be a limit to the number of mutable and selectable sites which, when exhausted, could prove disadvantageous to viral survival. The speed, at which novel SARS-CoV-2 mutants are selected and dispersed around the world, could have implications for the development of vaccines and therapeutics, according to a new study co-authored by Christina Ramirez, UCLA Fielding School of Public Health professor of biostatistics, and colleagues. BACKGROUND Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was first identified in Wuhan, China late in 2019. Nine months later (Sept. 23, 2020), the virus has infected almost 32 million people around the world and caused at least 971,000 (3.07 %) fatalities in 220 countries and territories. Research on the genetics of the SARS-CoV-2 genome, its mutants, and their penetrance, can aid future defense strategies. METHOD By analyzing sequence data deposited between December 2019 and end of May 2020, researchers compared nucleotide sequences of 570 SARS-CoV-2 genomes from China, Europe, the United States, and India to the sequence of the Wuhan isolate. IMPACT It will now be important to correlate the identified hotspot mutations with the course and outcome of individual infections in humans. This demanding problem has not yet been tackled. Hopefully, the results of our study will provide a platform for those in SARS-CoV-2 research who take care of patients with SARS-CoV-2 infections. SARS-CoV-2 has the ability to mutate and, in its course of dissemination around the world, to select for distinct signal hotspot mutations depending on high rates of genome replication and complex environmental and genetic conditions in newly invaded territories. During its intercontinental journey, the exposure of SARS-CoV-2 to the 21st century’s repertoire of medical resources may have been an additional selective force. The impact of an increase in hotspot SARS-CoV-2 mutations on immunogenesis and the prospects for vaccine development might be experienced and will have to be examined in the future. AUTHORS Study authors are Stefanie Weber, Christina Ramirez, and Walter Doerfler JOURNAL The study is published as “Signal hotspot mutations in SARS-CoV-2 genomes evolve as the virus spreads and actively replicates in different parts of the world” in the November, 2020 edition of the peer-reviewed journal Virus Research, FUNDING This work was conducted under the auspices of the UCLA Fielding School of Public Health; initiation of this project was undertaken by Stefanie Weber and Walter Doerfler both at the Institute for Clinical and Molecular Virology at Friedrich Alexander University (FAU) in Erlangen-Nürnberg. No external funding was provided. The UCLA Fielding School of Public Health, founded in 1961, is dedicated to enhancing the public's health by conducting innovative research, training future leaders and health professionals from diverse backgrounds, translating research into policy and practice, and serving our local communities and the communities of the nation and the world. The school has 690 students from 25 nations engaged in carrying out the vision of building healthy futures in greater Los Angeles, California, the nation and the world.

Newswise — Testing self-collected saliva samples could offer an easy and effective mass testing approach for detecting asymptomatic COVID-19. Scientists at Hokkaido University and colleagues in Japan have demonstrated a quick and effective mass testing approach using saliva samples to detect individuals who have been infected with COVID-19 but are still not showing symptoms. Their findings were published in the journal Clinical Infectious Diseases. "Rapid detection of asymptomatic infected individuals will be critical for preventing COVID-19 outbreaks within communities and hospitals," says Hokkaido University researcher Takanori Teshima, who led the study. Many of the world's governments are showing reluctance to re-institute full national lockdowns as second waves of COVID-19 infections loom on the horizon. Testing and tracing systems will need to be ramped up in order to detect and isolate people who have the virus as early as possible. Teshima and colleagues tested and compared the nasopharyngeal swabs and saliva samples of almost 2,000 people in Japan who did not have COVID-19 symptoms. Two different virus amplification tests were performed on most of the samples: the PCR test, which is now well-known and widely available around the world, and the less commonly used but faster and more portable RT-LAMP test. The number of positive and negative results in all samples was very similar, with the nasopharyngeal swabs and saliva samples able to detect those with the infection in 77-93% and 83-97% of subjects, respectively. Both two tests were also able to identify those without the infection in greater than 99.9% of subjects. The virus loads detected in nasopharyngeal swab and saliva were equivalent and highly correlated. Teshima says, "PCR sensitivity is much higher than previously thought 70% that came from initial data of symptomatic patients." While finding both nasopharyngeal and saliva samples have high sensitivity and specificity to the SARS-CoV-2, Teshima says "Saliva testing has significant logistic advantages over the commonly used nasopharyngeal swab testing." "Self-collection of saliva is painless for examinees, and more importantly, it eliminates the close contact with the examiners, reducing the risk of viral exposure." "We also found that it is unlikely that the sensitivity of RT-LAMP is significantly less than that of the PCR test, suggesting that it might be a useful alternative for diagnosing COVID-19 infection, especially where diagnosis is required at the point of sample collection, like in sports venues or at airports," says Teshima. Researchers point to a limitation of the study that they did not follow up with clinical outcomes. Nonetheless, they suggest that the results give good indication that mass screening using self-collected saliva and rapid RT-LAMP testing could provide easy, non-invasive, quick and relatively accurate results, with minimal risk of viral transmission to healthcare workers.   Image Credit: Isao Yokota et al., Clinical Infectious Diseases, September 25, 2020 Both nasopharyngeal swab (NPS) and saliva testing showed high sensitivity and specificity to the SARS-CoV-2. (Isao Yokota et al., Clinical Infectious Diseases, September 25, 2020)