Body

A simple blood test may be able to determine how physically fit you are, according to a new study conducted by scientists at the Stanford University School of Medicine.

The test could complement treadmill tests, a more traditional clinical evaluation of fitness, and provide individuals with far more nuanced information about their body's molecular response to exercise.

The blood test is an offshoot of a complex study conducted by a team of researchers that took hundreds of thousands of molecular measurements from a group of individuals before and after exercising.

"Everybody knows exercise is good for you, but we really don't know what drives that at a molecular level," said Michael Snyder, PhD, professor and chair of genetics. "Our goal at the outset was to conduct a highly comprehensive analysis of what's happening in the body just after exercising."

The team tracked molecular markers of a wide array of biological processes, such as metabolism, immunity, oxidative stress and cardiovascular function. Hundreds of thousands of measurements from 36 study participants provided a window into the sea of chemical fluctuations the body experiences during intense exercise. To the scientists' knowledge, such comprehensive measurements of post-exercise molecular fluctuations have never been performed. What's more, the team saw that the participants who were most physically fit shared similar molecular signatures in their resting blood samples captured before exercise.

"It gave us the idea that we could develop a test to predict someone's level of fitness," said Kévin Contrepois, PhD, director of metabolomics and lipidomics in the Department of Genetics. "Aerobic fitness is one of the best measures of longevity, so a simple blood test that can provide that information would be valuable to personal health monitoring."

With the preliminary data, the team has created a proof-of-principle test, for which they've filed a patent application. The test is not currently available to the public.

A paper describing the study will be published May 28 in Cell. Snyder, who holds the Stanford W. Ascherman, MD, FACS, Professorship in Genetics, and Francois Haddad, MD, clinical professor of medicine, are co-senior authors of the study. Contrepois shares lead authorship with postdoctoral scholars Si Wu, PhD, and Daniel Hornburg, PhD, and with clinical assistant professor Kegan Moneghetti, MD, PhD.

A flurry of change

Snyder's team set out to better understand the molecular shifts that underlie changes in physical fitness. The gold standard of medical fitness assessments is a peak VO2 test, which measures a person's peak oxygen consumption during intense exercise and uses the score as a proxy for aerobic fitness. But Snyder and his team wanted more detail -- specifically, about the ways in which exercise initiates change at the molecular level.

They performed VO2 testing for 36 individuals, including Snyder, on a treadmill. Participants, both male and female, had an average body mass index of 29 kilograms/meter squared, and their age range was from 40 to 75 years old. Before the treadmill test, the researchers drew a baseline blood sample. Participants then donned an oxygen-measuring mask and ran at a slight incline until they reached peak oxygen consumption, at which point they stopped and got off the treadmill. The researchers took blood samples from participants 2 minutes, 15 minutes, 30 minutes and 60 minutes after they had reached their peaks.

"All of these measurements allow us to describe a choreography of molecular events that occur after physical exercise," Snyder said. "We know that exercise causes an array of physiological responses, such as inflammation, metabolism and hormone fluctuation, but these measurements allowed us to characterize those changes in unprecedented detail."

It turns out that in the first two minutes post-exercise, the body experiences an intense flurry of molecular activity. In most participants, molecular markers of inflammation, tissue healing and oxidative stress, a natural byproduct of metabolism, spiked sharply shortly after hopping off the treadmill, as their bodies began to recover. Molecular markers of metabolism varied, Snyder said. At 2 minutes, blood samples revealed evidence that the body was metabolizing certain amino acids for energy, but it switched to metabolizing glucose, a type of sugar, around 15 minutes. "The body breaks down glycogen as part of its exercise recovery response, so that's why we see that spike a little later," Snyder said. Glycogen is a form of stored glucose.

As part of the study, Snyder also compared the molecular response in individuals who were insulin resistant, meaning they're unable to process glucose properly, with the response in individuals who could process glucose normally. "The main difference we see is that insulin resistant individuals have a dampened immune response post-exercise," he said.

Blood test for fitness

Although it wasn't the team's original intent, they noticed some consistencies in the baseline measurements of the participants who performed better on the peak VO2 test. In these individuals, the researchers saw a strong correlation between a set of molecules and an individual's level of aerobic fitness. They discovered a collection of thousands of molecules -- including markers of immunity, metabolism and muscle activity -- that correlate with a person's aerobic fitness. "At this point, we don't fully understand the connection between some of these markers and how they are related to better fitness," Snyder said. The researchers hope to unravel those connections in a future investigation.

Snyder said that because the molecular profiling done in the study was so thorough, it wouldn't be practical for doctors to use in their clinics; it would be expensive and provide more information than necessary. But his team is working on whittling down the biomarkers to those that are most representative of a person's fitness level in an effort to make the test practical for broader use. Already, the team is developing an algorithm to select a subset of these molecules that are highly correlative to peak VO2 results, Contrepois said. As the researchers continue to optimize the fitness test, they hope it can one day be a faster, cheaper and more convenient way for people to objectively measure aerobic fitness.

From starling aberrations to self-turbulent fluids, 'active systems' encompass a wide family of phenomena in which individual objects propel themselves forward, allowing them to display intriguing collective behaviours. On microscopic scales, they are found in groups of living organisms which move around by squirming, and are aligned with Earth's gravitational fields due to their bottom-heavy mass distributions. Through research published in EPJ E, Felix Rühle and Holger Stark at the Technical University of Berlin find that depending on their properties, these objects collectively spend most of their time in one of two states, between which some intriguing behaviours can emerge.

The duo's insights could help to explain the mysterious properties of some groups of microorganisms, including thin films of phytoplankton which are sometimes found in coastal regions, and algae which form 'dancing' clumps. They found that these collective behaviours are determined by the ability of the self-propelling objects to swim upwards against the gravitational force, and their degrees of bottom-heaviness. For lower values of these quantities, groups of swimmers will sink to the bottom of their container just like inactive dust grains; but for higher values, will instead collect at the top. In between these states, smaller clusters of swimmers group at the bottom, which are fed by plumes of sinking particles. Also, porous clusters of swimmers can form, which allow individual particles to escape.

Rühle and Stark made their discoveries using computer simulations involving around 900 bottom-heavy squirmers in a fluid. Through their advanced techniques, they were able to account for any interactions between the swimmers, as well as the properties of the fluid itself. The duo's results now offer fascinating new insights into the properties of active systems under the influence of gravity, and could help biologists to better understand the roles of certain microorganisms in natural ecosystems.

A new type of test that uses complex sugars to detect prostate cancer earlier and with greater accuracy is being developed by researchers at the University of Birmingham.

The test works by identifying sugars, known as glycans, in blood. These sugars are attached to protein molecules called PSA and are known to undergo distinct but subtle changes when cancer is present in the body.

Particular types of glycans are associated with different cancers - but until now, there has been no technology available to detect the glycans in an accurate, timely and sufficiently specific way.

Research led by a team in the University of Birmingham's School of Chemical Engineering, has now developed a technique that can identify glycans associated with cancer with unprecedented accuracy. The technology has been patented by University of Birmingham Enterprise.

It works by using a synthetic carbohydrate material to create a mould of the specific glycan. These 'receptors' are then fixed in position on a surface so they bind to that glycan, but not to any others.

Professor Paula Mendes, in the University of Birmingham's School of Chemical Engineering, is lead author on the paper. She explains: "What is really exciting about the technique we've developed is the ability to pinpoint glycans with such specificity. A PSA molecule can have 56 different sugars attached to it, but only four are associated with prostate cancer. With this test, we're able to identify those four with certainty."

The number of glycans identified in this way will show not only if cancer is present, but how aggressive or advanced the cancer is. The research results are published in Advanced Functional Materials and the team expects to begin applying the technique to clinical samples in the laboratory later this year.

A new test for prostate cancer is urgently needed because current tests are only able to give an indication of increased PSA in blood samples. This can give false positive results in around 50 per cent of cases. This is because a man's PSA level can become elevated for a number of different reasons, not necessarily related to cancer. In addition, around 25 per cent of men who do have prostate cancer do not have elevated PSA, so the test fails to diagnose these patients.

Professor Mendes says: "Many patients undergoing the PSA test will be falsely diagnosed, causing them be sent for further, more invasive tests, and this places a lot of stress on the patient, as well as being very expensive for health services. Just as worrying, many men have low levels of PSA that do not show up well in tests. By measuring the glycans, however, we can offer diagnoses that are much more precise, not only detecting cancer at an earlier stage, but identifying how aggressive it is too."

The team also hopes to be able to apply the technology to detecting other cancers and has already started to develop a test for ovarian cancer.

"Ovarian cancer is typically detected at a very late stage, when treatment options are very limited, and so survival rates are very low," explains Professor Mendes. "Because our test is highly specific, it should be possible to apply it to a number of different types of cancer."

The research was funded by Prostate Cancer UK, as part of the charity's Research Innovation Awards Scheme.

Dr David Montgomery, Director of Research at Prostate Cancer UK, said: "Early and accurate diagnosis of prostate cancer is critical to ensuring we cure more men of prostate cancer while reducing side effects from over treatment. While PSA can be a helpful test, It is often elevated in people who don't have prostate cancer and tells us nothing about how aggressive the disease might be in people who do.

"While at an early stage, this research could make PSA a much more specific and accurate way not only to diagnose prostate cancer, but also to tell who needs urgent treatment and whose cancer is less aggressive and can safely be watched. Ultimately, this could help us cure more men and harm fewer.

"What we need now is for fantastic research like this to be able to continue beyond the current Covid-19 pandemic. With labs closed and much of this research coming to a standstill, Prostate Cancer UK is asking for people to donate now to ensure we can continue to fund ground-breaking research to help more men with prostate cancer."

Philadelphia, May 18, 2020--COVID-19 social distancing measures, including the closure of schools and parks and the indefinite cancellation of team sports, have led to a nearly 60% decrease overall in pediatric fractures but an increase in the proportion of fractures sustained at home, according to a new study by researchers at Children's Hospital of Philadelphia (CHOP). The findings, published in the Journal of Pediatric Orthopaedics, suggest a need for increased awareness of at-home safety measures.

"Although the overall rate of fractures is down significantly during the COVID-19 pandemic, the proportion due to bicycle and trampoline injuries has gone up substantially," said Apurva Shah, MD, MBA, an orthopaedic surgeon in CHOP's Division of Orthopaedics and senior author of the study. "It is important to remind parents about the importance of basic safety precautions with bicycles and trampolines, as many children are substituting these activities in place of organized sports and school activities."

The research team gathered data on 1,735 patients who presented at CHOP with acute fractures between March 15 and April 15, 2020 and compared that information with patients who presented with fractures during the same timeframe in 2018 and 2019. The researchers found a nearly 2.5-fold decrease in the daily incidence of fracture cases during the pandemic compared to the pre-pandemic period. Sports-related fractures saw a particularly dramatic decline, accounting for only 7.2% of fracture cases during the pandemic versus 26% of all fracture cases in the same month in 2018 and 2019.

Despite these significant declines, the researchers found an increase of more than 25% in fractures occurring at home, which was accompanied by a 12% increase in fractures caused by high-energy falls, like those resulting from trampoline injuries, and bicycle injuries. With families spending more time at home due to social distancing guidelines, the researchers suggest this shift in injury location is a natural result of families finding alternative recreational activities for their children.

The decline in fracture incidence was bigger for some age groups than others. Patients aged 12 and over saw a five-fold reduction in the monthly number of fracture cases, whereas children aged 5 and under saw only a 1.5-fold decrease. The researchers surmise this is due to younger children substituting other active pursuits for pre-pandemic activities, like playground outings and other outdoor activities, whereas adolescents, who are more likely to play team sports, are making fewer of those substitutions.

The researchers did not find a significant uptick in the use of cast alternatives, like controlled ankle motion boots, during the pandemic, but they did see a 20% increase in the use of Velcro wrist splints for torus distal radius fractures, a buckle fracture near the wrist. The authors note these splints are a valuable option at a time when many patients are avoiding hospitals and clinics, as the splints are effective, widely available, and eliminate the need for a follow-up appointment for cast removal. Combined with an increase in telemedicine follow-up appointments, the research team said these sorts of alternatives can provide quality care for patients both now and in the future.

"This pandemic highlights new opportunities for improvement of patient care, as we observed significant increases in the use of telemedicine and prescription of generic Velcro wrist splints," Shah said. "These treatment trends may serve as the basis for more cost-effective fracture care long after the conclusion of the outbreak."

Worcester, Mass. - May 28, 2020 - A team of researchers led by Worcester Polytechnic Institute (WPI) Provost Wole Soboyejo has identified targeted drugs that reduced the sizes of hard-to-treat breast cancer tumors in mice without inducing the toxic side effects that are typically associated with conventional chemotherapy.

The researchers said in an article published in Scientific Reports that a molecular recognition unit attached to drugs specifically targeted "triple-negative" breast cancer tumors, which typically do not respond to targeted therapies. The targeted drugs eliminated or reduced the sizes of breast cancer tumors in laboratory experiments that were performed on mice. No toxic side effects were observed in the experiments.

"When injected into the bloodstream, only a small fraction of traditional chemotherapeutic drugs reaches tumors," Soboyejo said. "It usually takes relatively high concentrations of conventional cancer drugs to have therapeutic effects on tumors. Hence, such concentrations are often toxic to other cells. In our case, the targeting drugs were more effective at shrinking and eliminating triple-negative breast tumors in mice. They also eliminated tumors without inducing toxicity."

Breast cancer is the most commonly diagnosed cancer in women. Chemotherapy kills fast-growing tumor cells by flooding a patient's body with potent drugs, but the treatment often produces toxic side effects. Targeted therapy aims to reduce side effects by delivering chemotherapeutic drugs directly to breast cancer tumor cells. The drugs seek out and bind to specific cellular structures known as receptors.

Three common receptors that are over-expressed on the surfaces of breast cancer tumor cells are HER2, a growth factor, as well as estrogen and progesterone hormones. Most breast cancer treatments target HER2 receptors. However, between 10% and 17% of all breast cancers lack HER2, estrogen, and progesterone receptors. These "triple-negative" breast cancers are more prevalent in younger women, African American women, and African women.

Soboyejo, inspired by a relative's battle with breast cancer, previously studied luteinizing hormone-releasing hormone (LHRH) as a targeting mechanism to deliver magnetic nanoparticles to breast tumors. The targeted magnetic nanoparticles were found to improve the imaging of breast tumors in nude mice, a type of laboratory mouse. LHRH is a naturally occurring hormone in mammals. It is essential for reproduction.

More recently, Soboyejo began studying LHRH as a targeting mechanism for chemotherapeutic drugs. His work has been funded by WPI and the Pan African Materials Institute at the African University of Science and Technology (AUST) in Abuja, Nigeria, which is funded by the World Bank.

In this study, the researchers attached the chemotherapy drug paclitaxel to LHRH. They also attached prodigiosin, a natural substance with anti-cancer properties, to LHRH. Both combination molecules were tested against triple-negative breast cancer cells and tissues.

Soboyejo's team hopes to continue work on LHRH-targeted nanoparticles and therapeutic drugs, and to position them for human clinical trials on breast cancer patients. The group is also working to identify other targeted drugs and nanoparticles for the detection and treatment of other tumors.

"The fact that we could target triple-negative breast cancer in mice models is important. However, I think this method has major implications for targeted cancer treatment in general," Soboyejo said.

In 1844, multiple myeloma was first treated with a rhubarb pill and an infusion of orange peel. Since then, more than 15 drugs have earned FDA approval to treat multiple myeloma and with so many options, a major question has become what cocktail and sequence is best?

"These days people are going through ten lines of therapy for multiple myeloma and end up getting every drug we have. The question is when," says Daniel Sherbenou, MD, PhD, University of Colorado Cancer Center investigator and assistant professor in the CU School of Medicine Division of Hematology. "Patients' first remission is usually their best one, so you want to use the best drugs first. If you get the right drug first, a patient can be in remission five or more years, and that's the period when quality of life is best, just taking oral medication for their disease. So there's a lot of advantage for getting the sequencing right."

Currently, without a good way to predict which drugs will work, doctors often use three or more agents, hoping that some will offer benefit while assuming that some will not. The use of more drugs often leads to increased drug side effects. And in cases where patients are more frail and side effects are more dangerous (as is often the case in multiple myeloma), doctors and patients may have to pick only one or two drugs and cross their fingers their choices prove useful.

"Right now, the choice between three FDA-approved cocktails really comes down to personal provider preference," Sherbenou says. "In many cases, there's no rational way to choose."

Generally, the many multiple myeloma drugs fall into a few main categories: Drugs that adjust the immune system, proteasome inhibitors, and a relatively new drug, daratumumab, which attaches to a protein called CD38 that is overexpressed on multiple myeloma cells. Now the first paper published by Zach Walker and colleagues from the Sherbenou lab at University of Colorado Cancer Center uses strategies of drug development to predict which classes of drugs will offer the most benefit.

The team took a new approach.

"People have tried this before, but earlier studies purified myeloma cells away from the rest of the tumor. Once these cells are by themselves, their survival takes a dip even without treatment. If you have only 10 percent viability anyway, you only have small window to measure drug effects," Sherbenou says.

Importantly, purifying multiple myeloma cells into a dish takes them away from the immune system, and without the ecosystem of an immune system, it's impossible to test immunotherapies.

"Our approach was to culture whole bone marrow, so you get multiple myeloma cells along with immune system and other cells," Sherbenou says. "It worked much better and we were able to test immunotherapy effects."

Sherbenou calls his test Myeloma Drug Sensitivity Testing (My-DST). Basically, the test incubates liquid biopsies of a patient's disease and then treats the samples with the seven most effective drugs approved to treat multiple myeloma. The approach is especially possible in multiple myeloma, which requires a bone marrow biopsy and not a more invasive solid tumor biopsy to obtain a sample of the cancer for testing. Using 55 patient samples of multiple myeloma, the group was able to show that how well drugs kill cells in these samples predicted how well real patients responded to these drugs in the clinic.

"We were surprised at how well it worked," Sherbenou says.

In addition to using My-DST to help patients and doctors pick the best therapies, Sherbenou hopes to use the test to guide drug development.

"If you develop a new drug for multiple myeloma, the first test won't be with new patients, and they will be multiple-drug resistant. So you need to pinpoint just the patients who are still likely to benefit. We hope My-DST will help predict which drugs are most promising for a phase 1 clinical trials," Sherbenou says.

In addition to the publication of more studies fleshing out the science of My-DST, Peter Forsberg and Tomer Mark of the CU Plasma Cell Disorders Program also designing clinical trials around the test. In one trial, the group hopes to test the ability of My-DST to pick treatments that will benefit patients who have already been treated with multiple lines of therapy; in another trial, the group hopes to use My-DST to choose between the three FDA-approved cocktails for patients' first course of treatment.

"We have such a big menu of options for multiple myeloma - a lot of choices we're trying to distinguish between," Sherbenou says. "By choosing the exact one a patient gets, we hope to get them into a deeper response more rapidly."

HOUSTON - In an international trial led by researchers at The University of Texas MD Anderson Cancer Center, treatment with MK-6482, the small molecule inhibitor of hypoxia-inducible factor (HIF)-2a was well tolerated and resulted in clinical responses for patients with von Hippel-Lindau disease (VHL)-associated renal cell carcinoma (RCC).

The results of the Phase II trial were shared today in an oral presentation at the 2020 American Society of Clinical Oncology Annual Meeting by principal investigator Eric Jonasch, M.D., professor of Genitourinary Medical Oncology.

The trial met its primary endpoint and showed an objective response rate in RCC tumors per RECIST by independent review. The confirmed response rate was 27.9%. When also considering the eight patients with unconfirmed response, the objective response rate was 41.0%. Additionally, 86.9% of patients had a decrease in the size of their target lesions. The median time to response was 5.5 months.

"Patients with von Hippel-Lindau disease are at risk of developing several types of cancer and other tumors, and there are currently no approved therapies," said Jonasch "We are encouraged by the results of this clinical trial and look forward to seeing further study of MK-6482 as we work to make this treatment option available for patients with VHL disease."

VHL disease is a rare inherited mutation of the VHL gene. The disease is associated with tumors forming in multiple organs. Some of these tumors are benign, but they can grow and cause damage to organs. VHL also can cause cancerous tumors in the kidney or pancreas. RCC affects approximately 40% of people with VHL disease and is one of the most common causes of disease-related death in people with VHL disease.

The VHL mutation causes cells to lose their ability to respond to oxygen levels properly, and leads to a buildup of HIF proteins inside the tumor cell. This process incorrectly signals that the cells are starved of oxygen, causing the formation of blood vessels and driving tumor growth. The inactivation of the VHL tumor-suppressor protein also is observed in more than 90% of sporadic RCC tumors. MK-6482 directly targets HIF-2a, hindering cancer cell growth, spread and abnormal blood vessel development.

Treatment of VHL disease-associated renal tumors consists of active surveillance until surgery is required for tumors larger than 3?cm to prevent metastatic disease. Repeated surgical procedures can carry significant complications as many patients develop renal insufficiency. Surgery will not cure VHL disease patients with RCC; surgery only is intended to prevent death from metastatic kidney cancer.

"Therapy options that can delay or avoid the need for surgery by decreasing tumor size are needed," said Jonasch. "This agent could profoundly change the way we manage lesions in patients with VHL disease."

As of data cut-off, the single-arm clinical trial had enrolled 61 patients. The study enrolled adult patients with a germline mutation diagnosis of VHL disease, no prior systemic cancer therapy, measurable non-metastatic RCC tumors and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Patients received MK-6482 orally once daily until disease progression, unacceptable toxicity, or investigator's or patient's decision to withdraw. Tumor size was evaluated at screening and every 12 weeks thereafter. No patients had progressive disease on treatment and 58 patients (95.1%) remain on treatment.

Most treatment-related adverse events (AEs) were grade 1 or 2 in severity. Grade 3 AEs occurred in 9.8% of patients. There were no grade 4 or 5 treatment-related AEs reported. The most common adverse events were anemia (86.9%), fatigue (57.4%), headache (36.1%), dizziness (31.1%) and nausea (24.6%). Anemia was safely managed with long-acting erythropoietin injections.

"MK-6482 was well tolerated and had few side effects," said Jonasch. "This is the first therapeutic agent that has shown the efficacy and safety required to make it a real option for the management of patients with VHL disease."

Future studies to be considered include testing whether MK-6482 can prevent the development of new lesions in patients with VHL disease.

BOSTON--Researchers at Massachusetts General Hospital have uncovered an unexpected connection between an imbalance of electrons in liver cells and many metabolic problems that increase the risk for conditions such as cardiovascular disease and fatty liver disease. Their findings, published in the journal Nature, shine a light on the phenomenon known as reductive stress and how genetics and environmental factors such as diet influence this emerging disease risk factor.

Reductive stress occurs when cells build up an overabundance of electrons, which play an essential role in producing energy. "The food we eat tends to be very rich in electrons," says Vamsi Mootha, MD, of Mass General's Department of Molecular Biology, and senior author of the Nature study. "But if there's an imbalance between the supply and demand for those electrons--specifically, an excess supply--you can get reductive stress."

Eating a high-fat diet and consuming alcohol can cause reductive stress in liver cells. While reductive stress has been linked to certain rare genetic disorders known as mitochondrial diseases, its role in more common conditions has not been well studied.

Mootha's colleague and the lead author of the study, Mass General hepatologist Russell Goodman, MD, DPhil, oversaw a team that administered a genetically engineered enzyme called LbNOX to the livers of lab mice that had been given alcohol. "Alcohol generates a ton of electrons, and that causes a lot of reductive stress," says Goodman. Yet LbNOX prevented the mice from developing reductive stress. "The study showed that we can use this genetic tool to control reductive stress in the liver," he says. "We can give it and take it away."

The team identified a metabolite in the blood called alpha-hydroxybutyrate that rose when electrons built up in liver cells. This intrigued the investigators, since alpha-hydroxybutyrate levels are associated with insulin resistance, a risk factor for type 2 diabetes, and obesity. Previous genetic analysis linked alpha-hydroxybutyrate levels in humans to a variant in a gene called GCKR, which occurs in about 50 percent of people and seems to affect risk for many diseases and unhealthy traits, such as fatty liver disease and elevated levels of blood fats called triglycerides. They showed that the GCKR mutation in mouse liver cells was associated with high levels of alpha-hydroxybutyrate, linking it to reductive stress.

Importantly, this study (which was funded by the Marriott Foundation) found that treating reductive stress with LbNOX lowered levels of triglycerides, which increase the risk for cardiovascular disease, and improved metabolic factors, including insulin resistance.

Mootha believes alpha-hydroxybutyrate could be used as a biomarker to test for reductive stress and that LbNOX may one day serve as a treatment for diseases caused by metabolic dysfunction. "LbNOX is empowering a new class of studies we call 'causal metabolism'," says Mootha. "They are allowing us, for the first time, to manipulate metabolism in living organisms and see what the consequences are."

Pairing a blood-thinning drug with aspirin daily for patients who have an angioplasty with a stent can contribute to better health outcomes, including lower risk of death, than aspirin alone, according to a recent study by cardiologists at the University of Alberta and Mazankowski Alberta Heart Institute.

Led by Kevin Bainey, a U of A interventional cardiologist and associate professor, the work builds on the COMPASS study that followed 27,400 people from around the world with stable coronary or peripheral artery disease. It shows that the combination of a small dose of the blood-thinning drug rivaroxaban twice daily plus 100 mg of aspirin once daily was significantly better than only one or the other in preventing heart attacks, strokes and death.

"There are a lot of patients with stable coronary disease who have stents in their heart arteries. Most commonly, the only blood thinner they are taking is aspirin," Bainey said.

What he wanted to know was whether those patients would benefit in the same way from the COMPASS dual-pathway approach.

Bainey and colleagues from around the world focused on a subgroup of nearly 10,000 COMPASS participants who had previously had an angioplasty with a stent inserted in blood vessels in the heart, and found that the treatment did lead to better health outcomes in that group, reducing heart attacks, strokes and deaths.

The interesting twist, Bainey said, is that his study also showed that the time between a patient's prior coronary intervention and starting dual pathway treatment made no difference in improving the health outcomes for these patients.

"It didn't matter if a patient had a stent a year ago or 10 years ago; with this dual pathway strategy you still see an improvement in outcomes and, most importantly, an improvement in survival," he said.

The dual-pathway treatment has been approved by Health Canada for use in patients with chronic coronary or peripheral disease. Thanks in part to COMPASS, Bainey is hoping his research will encourage more cardiologists and physicians to prescribe it to patients with or without a prior stent.

"As an interventional cardiologist, I put a lot of stents in people, and the question in my mind is always, 'Can we improve upon their outcomes and reduce their residual risk?'" Bainey said. "We're always trying to find ways to optimize their therapy.

"So when you have a drug that has been shown to improve a patient's survival, you really hope that it takes off as standard of care."

Top stroke experts have issued new guidance to ensure stroke patients receive safe, timely care while preventing the transmission of COVID-19.

The guidelines urge the use of telemedicine to speed treatment and advise EMS crews how to determine the best facility to treat the patient's needs. The recommendations, from the American Heart Association's Stroke Council, come amid increasing concerns that stroke patients are delaying seeking care because of fear of COVID-19. Such delays can have catastrophic consequences, including death.

"Even during the COVID-19 pandemic, patients should continue to seek immediate care for life-threatening and emergency conditions, and call 911 for any new signs or symptoms of stroke," said UVA Health stroke expert Andrew Southerland, MD, one of the guidelines' authors. "As the only certified Comprehensive Stroke Center in Charlottesville and Central Virginia, UVA has the necessary resources to ensure both patient safety and provide the highest level of care for stroke patients. Seeking emergency care for a stroke can help save lives and reduce the risk of long-term neurologic injury and resulting disability."

The Importance of Speedy Stroke Care

With stroke, every minute counts, and speedy care can be the difference in life and death. It can also prevent lifelong disability. For that reason, Southerland and other telemedicine experts at UVA have worked with local EMS personnel to pioneer the use of the technology for pre-hospital care. They've placed tablets inside ambulances to connect first responders with UVA stroke experts, allowing stroke care to begin even before the patient arrives at the hospital. The new guidelines suggest this approach should be used widely.

The COVID-19 pandemic, however, adds an extra layer of complexity for first responders. In addition to the need for appropriate personal protective equipment, EMS crews must assess whether each patient has the coronavirus, the new guidelines note.

When possible, EMS workers should screen patients using free tools available online, the guidelines recommend. Responders should have a protocol in place in case the screening is positive or if the patient is incapacitated and can't be screened. The receiving hospital should be notified as well.

Stroke patients with COVID-19 are more likely to require a ventilator and intensive care, so emergency crews should consider taking patients to a hospital with the capacity to provide that level of care, the guidelines note. Emergency crews also may need to consider hospital capacity based on the number of cases in their region. And they may want to bypass emergency rooms to lessen exposure risk.

"During the COVID-19 pandemic," the guidelines state, "it is more important than ever to ensure that the patient is transferred to the right hospital the first time around."

In all of this, communication between emergency crews and the receiving hospitals is key, the guide's authors say.

"Now more than ever, during the COVID-19 pandemic, we need to work collaboratively and support our emergency medical services providers working day and night on the front lines for our community," Southerland said. "To achieve this, we must optimize communication and prehospital care for patients. Nowhere is this more important than in rural networks like surrounding areas in Central Virginia."

A team led by researchers at Baylor College of Medicine in collaboration with Medterra CBD conducted the first scientific studies to assess the potential therapeutic effects of cannabidiol (CBD) for arthritic pain in dogs, and the results could lead the way to studying its effect in humans. Researchers focused first on these animals because their condition closely mimics the characteristics of human arthritis, the leading cause of pain and disability in the U.S. for which there is no effective treatment.

Published in the journal PAIN, the study first showed both in laboratory tests and mouse models that CBD, a non-addictive product derived from hemp (cannabis), can significantly reduce the production of inflammatory molecules and immune cells associated with arthritis. Subsequently, the study showed that in dogs diagnosed with the condition, CBD treatment significantly improved quality of life as documented by both owner and veterinarian assessments. This work supports future scientific evaluation of CBD for human arthritis.

"CBD is rapidly increasing in popularity due to its anecdotal health benefits for a variety of conditions, from reducing anxiety to helping with movement disorders," said corresponding author Dr. Matthew Halpert, research faculty in the Department of Pathology and Immunology at Baylor. "In 2019, Medterra CBD approached Baylor to conduct independent scientific studies to determine the biological capabilities of several of its products."

In the current study, Halpert and his colleagues first measured the effect of CBD on immune responses associated with arthritis, both in human and murine cells grown in the lab and in mouse models. Using Medterra tinctures, they found that CBD treatment resulted in reduced production of both inflammatory molecules and immune cells linked to arthritis.

The researchers also determined that the effect was quicker and more effective when CBD was delivered encapsulated in liposomes than when it was administered 'naked.' Liposomes are artificially formed tiny spherical sacs that are used to deliver drugs and other substances into tissues at higher rates of absorption.

Halpert and colleagues next assessed the effect of naked and liposome-encapsulated CBD on the quality of life of dogs diagnosed with arthritis.

"We studied dogs because experimental evidence shows that spontaneous models of arthritis, particularly in domesticated canine models, are more appropriate for assessing human arthritis pain treatments than other animal models. The biological characteristics of arthritis in dogs closely resemble those of the human condition," Halpert said.

Arthritis is a common condition in dogs. According to the American Kennel Club, it affects one out of five dogs in the United States.

The 20 client-owned dogs enrolled in the study were seen at Sunset Animal Hospital in Houston. The dog owners were randomly provided with identical unidentified medication bottles that contained CBD, liposomal CBD, or a placebo. Neither the owners nor the veterinarian knew which treatment each dog received.

After four weeks of daily treatment, owners and veterinarians reported on the condition of the dogs, whether they observed changes in the animals' level of pain, such as changes related to running or gait. The dogs' cell blood count and blood indicators of liver and kidney function also were evaluated before and after the four weeks of treatment.

"We found encouraging results," Halpert said. "Nine of the 10 dogs on CBD showed benefits, which remained for two weeks after the treatment stopped. We did not detect alterations in the blood markers we measured, suggesting that, under the conditions of our study, the treatment seems to be safe."

Black non-Hispanic and Hispanic women with opioid use disorder (OUD) are significantly less likely to receive or to consistently use any medication to treat their opioid use disorder during pregnancy than their white non-Hispanic counterparts, according to a new study from Massachusetts General Hospital (MGH).

Based on a population-level sample of women with OUD in the State of Massachusetts, the researchers found racial and ethnic disparities in the range of 60 to 75 percent, despite the fact use of the medications such as methadone and buprenorphine is associated with improvement in outcomes of both mothers and infants.

"We found evidence of striking racial and ethnic differences in terms of medication receipt, continuation of medication use, and type of medication received by pregnant women with OUD," said Davida Schiff, MD, with the Division of General Academic Pediatrics, MassGeneral Hospital for Children, and lead author of the study, published in JAMA Network Open.

These findings have important implications for our healthcare system as opioid use disorder has increased four-fold over the past decade in the United States, mirroring the increased use of opioids in the general population.

The retrospective study by led by the MGH team and collaborators at the Massachusetts Department of Public Health is the first to explore racial/ethnic differences in the use of medication for OUD during pregnancy. Researchers examined a statewide cohort of more than 5,200 pregnant women with OUD from 2011 to 2015 (87 percent were white non-Hispanic).

They found that black women were 63 percent less likely and Hispanic women 58 percent less likely than white women to receive methadone (dispensed only in federally regulated methadone clinics) or buprenorphine (most commonly prescribed by physicians in office-based settings) for OUD while pregnant, after adjusting for other maternal characteristics.

Those disparities were even greater among women less than 25 years of age. The study further revealed that black non-Hispanic women were 76 percent less likely and Hispanic women 66 percent less likely than white non-Hispanic women to receive consistent treatment for more than six months prior to delivery.

Dr. Monica Bharel, MD, MPH, Commissioner of the Massachusetts Department of Public Health (DPH) and co-author of the study, remarked that "data from our innovative Public Health Data Warehouse has enabled us to gain a deeper understanding of the opioid crisis and document inequities in treatment during pregnancy. This collaboration is an example of our data-driven approach to better understand the treatment experience for women of color and to improve outcomes for women and children."

During pregnancy, medication along with behavioral therapy is recommended for the management for women with opioid use disorder. This regimen has been proven effective in adherence to prenatal care and in pregnancy outcomes, including lower rates of preterm birth and low birth weight, and reductions in maternal relapse and overdose.

And while pregnancy provides a motivational opportunity for women with OUD to initiate treatment and increase their engagement with health care services, the MGH study suggests that for all women, consistent use of medications during pregnancy in the second and third trimesters was low, at only 38 percent.

Yet for women of color, the rates were significantly lower. Deterrents may include increasingly punitive public policy toward pregnant women who use drugs, racial discrimination by clinicians, cultural differences around medication use, perceived stigma of drug use during pregnancy, and minimal social supports.

"Even in a state like Massachusetts which has a well-funded addiction treatment system and universal insurance coverage in pregnancy, we identified significant racial and ethnic disparities, suggesting that individual and systemic factors are discouraging women from receiving addiction treatment," says Schiff, a pediatrician and medical director of the HOPE Clinic at MGH that cares for women and families with substance use disorders.

"More than half of all states, including Massachusetts, have either punitive policies toward women who use drugs during pregnancy and/or mandatory reporting of their cases to child protective services, including women who receive medication treatment for OUD. These policies, which disproportionately affect communities of color, are a deterrent to engaging in care. We must replace them with a public health approach that provides resources and true support to all women impacted by substance use disorder."

A study by University of Cincinnati researchers and four Italian institutions reviewing neuroimaging and neurological symptoms in patients with COVID-19 may shed light on the virus's impact on the central nervous system.

The findings, published in the journal Radiology, reveal that altered mental status and stroke are the most common neurological symptoms in COVID-19 patients, which authors say could help physicians notice "red flags" earlier.

"Studies have described the spectrum of chest imaging features of COVID-19, but only a few case reports have described COVID-19 associated neuroimaging findings," says lead author Abdelkader Mahammedi, MD, assistant professor of radiology at UC and a UC Health neuroradiologist. "To date, this is the largest and first study in literature that characterizes the neurological symptoms and neuroimaging features in COVID-19 patients. These newly discovered patterns could help doctors better and sooner recognize associations with COVID-19 and possibly provide earlier interventions."

Researchers in this study investigated neurological symptoms and imaging findings in patients from three major institutions in Italy: University of Brescia, Brescia; University of Eastern Piedmont, Novara; and University of Sassari, Sassari. Italy was the second epicenter of the spread of COVID-19, resulting in over 30,000 deaths.

The study included images from 725 hospitalized patients with confirmed COVID-19 infection between Feb. 29 and April 4. Of these, 108 (15%) had serious neurological symptoms and underwent brain or spine imaging. Most patients (99%) had brain CT scans, while 16% had head and neck CT imaging and 18% had brain MRI.

Investigators found that 59% of patients reported an altered mental state and 31% experienced stroke, which were the most common neurological symptoms. Patients also experienced headache (12%), seizure (9%) and dizziness (4%), among other symptoms.

"Of these 108 patients, 31, or 29%, had no known past medical history. Of these, aged 16 to 62 years, 10 experienced stroke and two had brain bleeds," Mahammedi says. "Seventy-one, or 66%, of these patients had no findings on a brain CT, out of which 7 of them (35%) brain MRI showed abnormalities."

He adds that altered mental status was more common in older adults.

While results show that the neuroimaging features of patients with COVID-19 vary, and an altered mental status and stroke are the most prevalent in patients, Mahammedi says this study reveals that there are other conditions to be on the lookout for.

"This topic definitely needs more research," he says. "Currently, we have a poor understanding of the neurological symptoms in COVID-19 patients, whether these are arising from critical illness or from direct central nervous system invasion of SARS-CoV-2. We hope further study on this subject will help in uncovering clues and providing better interventions for patients."

CLEVELAND, Ohio (May 26, 2020)--Dairy products provide more bone-beneficial nutrients than any other food group. Yet a new study based on data from the Study of Women's Health Across the Nation (SWAN) shows that during the menopause transition, when bone loss is accelerated, they offer little benefit in preventing bone mineral density loss or fractures. Study results are published online in Menopause, the journal of The North American Menopause Society (NAMS).

Growing up, children are often encouraged to drink milk. That's because dairy products contain more than 12 essential nutrients that promote bone mineralization, including calcium, phosphorus, vitamin D, and high-quality protein. Unfortunately, as women enter the menopause transition, bone loss accelerates and may lead to osteoporosis. According to SWAN data, this bone loss is not slowed down by the consumption of dairy products nor is fracture risk mitigated.

The new study specifically looked at the effect of dairy intake on femoral and spine bone mineral density. It is one of the few studies dedicated to examining how dairy consumption affects a woman's risk of bone loss and fractures across the menopause transition. Because two of the greatest risk factors for osteoporosis--age and sex--are beyond a woman's control, there is an increased focus on possible modifiable risk factors to slow this irreversible, age-related, progressive, degenerative skeletal disease that makes a woman more susceptible to bone fractures. Women are at greater risk for osteoporosis than men, and the risk increases significantly as women age.

Study results appear in the article "Dairy intake is not associated with improvements in bone mineral density or risk of fractures across the menopause transition: data from the Study of Women's Health Across the Nation."

"This study adds to the existing, albeit inconsistent, data suggesting a lack of benefit from dairy intake on bone mineral density and fracture risk. However, there are many other health benefits of a Mediterranean-type diet rich in fruits, vegetables, and whole grains, as well as lean protein such as fish and low-fat dairy. In addition, regular weight-bearing exercise, such as walking or jogging, can help maintain bone strength, and activities that improve strength and balance, such as yoga and tai chi, may help prevent falls," says Dr. Stephanie Faubion, NAMS medical director.

The novel coronavirus pandemic has caused an increased demand for antimicrobial treatments that can keep surfaces clean, particularly in health care settings. Although some surfaces have been developed that can combat bacteria, what's been lacking is a surface that can also kill off viruses. Now, researchers have found a way to impart durable antiviral and antibacterial properties to an aluminum alloy used in hospitals, according to a report in ACS Biomaterials Science & Engineering.

Among other mechanisms, viruses and bacteria can spread when a person touches a site where germs have settled, such as a doorframe, handrail or medical device. A healthy person can often fight off these bugs, but hospital patients can be more vulnerable to infection. The number of hospital-acquired infections has been on the decline in the U.S., but they still cause tens of thousands of deaths every year, according to the U.S. Department of Health and Human Services. Chemical disinfectants or coatings containing hydrophobic compounds, silver ions or copper can reduce infectious contaminants on surfaces, but these treatments don't last. However, nature has developed its own solutions for battling microorganisms, including microscopic structural features that render some insect wings lethal to bacteria. Scientists have replicated this effect by forming surfaces covered with minute pillars and other shapes that distort and kill bacterial cells. But Prasad Yarlagadda and colleagues wanted to inactivate viruses as well as bacteria, so they set out to generate a novel nanoscale topography on long-lasting, industrially relevant materials.

The team experimented with disks of aluminum 6063, which is used in doorframes, window panels, and hospital and medical equipment. Etching the disks with sodium hydroxide for up to 3 hours changed the initially smooth, hydrophobic surface into a ridged, hydrophilic surface. Bacteria or viruses were then applied to the etched disks. Most of the Pseudomonas aeruginosa and Staphylococcus aureus bacteria were inactivated after 3 hours on the surface, while viability of common respiratory viruses dropped within 2 hours; both results were better than with plastic or smooth aluminum surfaces. The disks retained their effectiveness even after tests designed to mimic hospital wear and tear. The researchers note this is the first report to show combined antibacterial and antiviral properties of a durable, nanostructured surface that has the potential to stop the spread of infections arising from physical surfaces in hospitals. This strategy could be extended to surfaces in other public areas, such as cruise ships, planes and airports, they say. The team is now studying the effects of their nano-textured aluminum surfaces on the novel coronavirus.