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DALLAS, Feb. 12, 2020 -- In patients unable to have the clots that caused their stroke dissolved or removed, a promising new stimulation treatment that increases blood flow to the brain may become an option, according to two preliminary studies to be presented at the American Stroke Association's International Stroke Conference 2020 - Feb. 19-21 in Los Angeles, a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health. Researchers also found the treatment improved hand strength in those with minor strokes and may decrease disability in patients with severe stroke.

Two prior trials of the stimulation of the sphenopalatine ganglion (SPG), at the back of the nose, showed beneficial effects in patients with stroke. Leveraging prior pivotal randomized controlled trial results, one of the new studies analyzes the same patient group to quantify the full range of benefit at 3 months. Building on a prior investigation assessing the stimulation therapy's immediate physiologic effects, the other new study determined the range of patients who show improved brain blood flow and motor function during stimulation.

"The stimulation treatment involves inserting a toothpick-sized electrode through a tiny opening in the upper palate of the mouth, positioning it very close to the SPG that sends nerves to blood vessels going to the brain. Stimulating that cluster of nerve cells causes blood vessels to dilate and enhance collateral blood flow to the brain in stroke patients without removing the clot that caused the stroke," said Jeffrey L. Saver, M.D., an author of both studies and professor of neurology at The David Geffen School of Medicine at the University of California, Los Angeles.

Assessing the True Impact-24b: Magnitude of benefit of Sphenopalatine Ganglion Stimulation for acute ischemic stroke with confirmed cortical involvement (Oral Presentation 11/Ordonez)

Researchers performed a new analysis of data from a randomized trial in order to estimate the extent of benefit of SPG stimulation among patients with stroke involving the brain's cortex, the outer part of the brain that plays an important role in consciousness and is thought to benefit when collateral blood flow around a clot-caused stroke is enhanced.

The study analyzed the full range of disability outcomes for 520 patients with confirmed low blood flow in the cortex who were ineligible for treatments to dissolve or remove a clot, usually because they had arrived at the hospital too late or the therapies were not available at that location. As part of the trial, 244 received SPG stimulation, and 276 received a control procedure involving vibrations with no actual electrical stimulation of the area. SPG stimulation was initiated 8-24 hours after stroke symptoms began.

After three months, researchers estimate that out of every 1,000 patients treated with SPG stimulation:

146 more will be less disabled; and

76 more will be functionally independent (able to walk and take care of their own basic needs).

"Even for patients who are not candidates to receive clot-dissolving drugs or to have the clot removed, we may now have other options in the future. This is good news, because while stroke treatment has really come forward in the last 20 years with regards to reopening and restoring blood flow, we've lagged behind in figuring out what to do for patients who are ineligible to receive the standard treatments," said Fausto Ordonez, M.D., lead author of the study and a vascular neurology fellow at the University of California, Los Angeles.

Diverse patients show physiologic benefit from refined Sphenopalatine Ganglion electrode placement and stimulation level selection to augment blood flow and neurologic function in acute ischemic stroke (The Impact-24m Trial) (Oral Presentation 114/Saver)

In this study, researchers assessed improvements in SPG stimulation techniques and early physiologic effects in 50 patients with anterior circulation ischemic strokes presenting 8-24 hours after last known well time and with mild deficits who were not eligible for clot-dissolving drugs or clot removal, either because their symptoms were too mild or they arrived at the hospital too long after the onset of stroke symptoms.

Using electrodes and CT scans to guide placement, it takes minutes to correctly implant the stimulation electrodes. Because the SPG also sends nerves to the face and the tear ducts, the proper amount of stimulation for each person could be comfortably determined by monitoring facial tingling or tear production.

Researchers found:

During SPG stimulation (tested on the second day of five days of treatment), blood flow to the brain and head increased by an average of 44%;

During stimulation, grip strength in the weaker arm increased 26%, and pinch strength increased 42%;

After seven days after treatment, recovery in the patients who received SPG stimulation was significantly better (improved total neurologic deficit scores) than matched controls from previous studies of other treatments; and

Benefits were evident no matter the age, sex, severity of stroke, time before treatment or which side of the body had weakness due to the stroke.

"SPG stimulation substantially increases brain blood flow and improves neurologic function across a broad range of patients when treatment begins up to 24 hours after stroke onset. This helps to explain why it is emerging as a potentially important new therapy for severe ischemic stroke," said Saver, who is also a member of the American Heart Association Stroke Systems of Care Advisory Group.

Since none of the patients in both studies received clot-busting medications or had their clots mechanically removed, it is unclear whether SPG stimulation could also benefit patients who received those treatments.

"Currently, the guidelines-based stroke treatments aim to remove the clot to restore blood flow. In these studies of SPG stimulation, the clot that's blocking blood flow is left untreated, and the SPG treatment is used to enhance collateral blood flow around the blockage. Potentially, SPG treatment could also preserve blood flow and brain tissue while a patient is being transferred to a hospital that can complete the clot removal treatment," Saver said.

DALLAS, Feb. 12, 2020 -- Seizures may be linked to a higher risk of death or disability in adults who have had a severe ischemic stroke, according to preliminary research to be presented at the American Stroke Association's International Stroke Conference 2020 - Feb. 19-21 in Los Angeles, a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

Ischemic stroke occurs when blood vessels leading to the brain are blocked. Seizures are abnormal brain activity that may cause uncontrollable shaking movements, loss of consciousness and confusion. Ischemic stroke patients who had seizures within seven days after their stroke were at higher risk of seizure recurrence and of being diagnosed with epilepsy.

"In the United States, stroke is the most common cause of epilepsy in adults. In Mexico, stroke is now the leading cause of epilepsy in adults as well," said Erwin Chiquete, M.D., Ph.D., lead study author and a neurologist and researcher at The Salvador Zubiran National Institute of Medical Sciences and Nutrition in Mexico City. "However, we suspect that seizures and epilepsy in stroke patients are still under-recognized by physicians."

In this study, researchers identified risk factors that predict the possibility of developing seizures or epilepsy (recurring seizures) following a severe stroke, and then assessed the impact of post-stroke seizures on death or disability up to one year after stroke.

Researchers analyzed electronic medical records data of 1,246 hospital patients without epilepsy upon admission, aged 18 to 94 (85% over age 40) and treated for acute ischemic stroke in 59 centers located in Mexico. After following the patients for 12 months, researchers found:

8% of stroke survivors suffered acute seizures within a week of their stroke, and almost 5% of these patients had at least one more seizure during the 12-month follow-up period.

Patients 18 to 40 years old were the most vulnerable group of stroke survivors. More than 13% of these patients developed recurrent seizures and were diagnosed with epilepsy.

Patients younger than 65 were 69% more likely to develop seizures than older patients.

The larger the injury to the brain from the stroke, the greater the likelihood of having a seizure. The odds of developing seizures were more than two times higher in people with severe brain injury from stroke and in those who had a second stroke.

Those who developed acute seizures were 37% more likely to die or develop physical and/or mental disabilities within one year following their stroke.

Other factors that significantly increased risk of death or disability included being over age 65, severity of stroke, heart failure and atrial fibrillation.

"We think that the secondary prevention of ischemic stroke and controlling seizures with anti-epileptic medication during the twelve months after stroke are very important to prevent death and to decrease disability," Chiquete said. "Our research suggests that severe ischemic stroke can cause epilepsy in a higher percentage of patients than we originally thought or has been shown in previous studies."

A tiny molecule of RNA - known as 'micro RNA' - plays a key role in 'rewiring' cancer cells so they can resist the effects of chemotherapy, a new study reveals.

The discovery opens up the possibility of creating new cancer drugs that target this micro RNA molecule, rather than more conventional treatments that block the action of proteins.

Scientists at The Institute of Cancer Research, London, found that a type of micro RNA known as MIR1249 plays a key role in allowing bile duct cancers to resist chemotherapy.

Micro RNAs, unlike other forms of RNA, don't help to translate the DNA code into proteins, but instead seem to be crucial for controlling the signalling networks within cells.

The researchers hope that MIR1249 could be a potential target for new drugs in bile duct cancer that could make chemotherapy much more effective. Bile duct cancer is very hard to treat and there is an urgent need to develop new therapies.

The researchers also believe that this mechanism driving resistance may be shared with other cancer types - raising the possibility that drugs to counteract it could have wider benefits.

The study is published in the journal Hepatology and released today (Wednesday) on Bile Duct Cancer Awareness Day. It was funded by The Institute of Cancer Research (ICR) as well as the European Union, Cancer Research UK, Pancreatic Cancer Action and the Italian Foundation for Cancer Research AIRC.

The study reveals that MIR1249 is able to 'rewire' the so-called WNT signalling network, which plays an important role in some healthy cells, and can be co-opted by cancer cells.

The WNT network is involved in the upkeep of stem cells - cells with the ability to self-renew and develop into many different cell types.

But when rewired, it seems to give cancer cells the features of stem cells, allowing them to become more resistant to treatment and able to survive the onslaught of chemotherapy.

The study, which involved mice and human tissue samples, revealed that by blocking MIR1249 activity, cancer cells became more sensitive to chemotherapy and responded better to treatment.

The researchers also found that 41 per cent of bile duct cancers had increased levels of MIR1249, suggesting it could be playing an important role within these tumours. In support of this idea, MIR1249 was also statistically associated with poorer survival outcome.

The next step will be to create drugs that could act against MIR1249, with the aim of preventing cancers from developing drug resistance and resensitising them to chemotherapy.

The ICR - a charity and research institute - is focused on understanding and combating cancer's ability to evolve and become drug resistant. It has less than £10 million still to raise for a new Centre for Cancer Drug Discovery, which will house an ambitious 'Darwinian' drug discovery programme to create new anti-evolution treatments.

Study leader Dr Chiara Braconi, who carried out the research as Clinician Scientist at The Institute of Cancer Research, London, and is now Lord Kelvin Adam Smith Reader in the Institute of Cancer Sciences at the University of Glasgow, said:

"Our study shows the crucial role played by a piece of micro RNA in rewiring the network of signals within cancer cells and helping them to resist the effects of chemotherapy. It identifies MIR1249 as a potential drug target in bile duct cancers and possibly other tumour types, and opens up what could be an exciting new avenue of treatment.

"It's remarkable how such a tiny piece of RNA can play such a significant role in rewiring cancer cells so that they can resist chemotherapy. There is growing interest in the idea of developing drugs against RNA rather than against proteins, as studies like ours show the important role of micro RNA in cell signalling."

Study co-author Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"Bile duct cancer is becoming increasingly common around the world and survival rates are very poor, so there is an urgent need to develop better therapies for people with advanced disease whose treatment stops working. This new study shows the potential of targeting molecules called micro RNAs as a new form of treatment for drug-resistant cancers.

"At the ICR, we believe overcoming cancer evolution and drug resistance is the biggest challenge we face today in the field of cancer research. Through our new Centre for Cancer Drug Discovery, we are aiming to find new 'anti-evolution' treatments that can offer long-term control or cure even for advanced cancers."

Sal Cheema, 42, from Uxbridge, who was diagnosed with stage 4 bile duct cancer in 2018, said:

"I had chemotherapy for eight months which kept my cancer at bay. But within six weeks, I was devastated to learn that the cancer had spread to my lymph nodes.

"Bile duct cancer is rare, yet the incidence is increasing and it's not known why. This cancer is also affecting younger people more and more, so it's imperative that this specific research continues - not only for bile duct but other cancers too.

"There are very few treatment options for bile duct cancer patients, so I'm elated to hear of this research and discovery as it could open up a whole new way of targeting the cancer. More targeted treatments with fewer side effects are vital - these findings are very promising for people like me."

Sarah, a military veteran living on the coast of South Carolina, knew she had a problem. The opioids prescribed for her pain were becoming a headache of their own.

"We trust our doctors. I went to my pain management doctor and said, 'I feel like I'm getting addicted to this. We have a problem. I'm waking up sick.' And instead of decreasing my medication, he just added another medication on top of it."

Her opioid use disorder became an even bigger problem when she got pregnant. But Sarah, who asked that her last name not be used to protect her privacy, got help at MUSC Health in Charleston. A psychiatrist and an OB-GYN worked together to coordinate her care.

Sarah was one of the lucky ones.

Nationally, less than 20% of pregnant women with opioid use disorder get treatment. Not getting treatment has been linked to poor fetal growth, preterm birth, birth defects and even the death of the mother or child. Babies born to mothers who use opioids, even under the supervision of doctors, may also suffer from neonatal abstinence syndrome, or NAS.

But psychiatrist Constance Guille, M.D., an associate professor in the Department of Psychiatry and Behavioral Sciences at the Medical University of South Carolina, said there are effective treatments. She and colleagues at MUSC have been studying the best ways to help women with opioid use disorder during and after pregnancy.

Their latest study focused on whether telemedicine, which uses technology to connect doctors with patients for online appointments, is another way to reach women who live too far away to get to Charleston on a regular basis. It was published Jain late January in JAMA Network Open.

In a trial involving 98 women at four obstetricians' offices, the researchers explored whether moms-to-be who saw doctors through telemedicine did as well as women who saw doctors in person for opioid use disorder treatment. All of the women saw the doctors in person for their first appointments, as required by law, because controlled substances were involved.

After that, Guille said there were no statistically significant differences in important maternal and newborn outcomes between the telemedicine group and the women who continued to see their doctors in person during and after their pregnancies.
That has important implications for mothers and children, Guille said. Through telemedicine, doctors can reach patients in rural areas, including people who don't have the time or money to go to bigger cities for treatment.

"Integrated, collaborative care, where obstetricians and psychiatrists can work together, is the ideal model for treatment of pregnant women with opioid use disorder. It's been really hard to create that model from a financial standpoint and because there aren't a lot of people with expertise in this area," Guille said.

"Being able to take the people who specialize in this area and maximize their reach to obstetric practices by telemedicine is just a really great way to get women lifesaving treatment for this chronic disease and reduce maternal opioid overdose deaths."

Not all obstetricians have a telemedicine option, but the number is increasing across South Carolina. MUSC is a key player in the expansion through its Center for Telehealth, one of only two National Telehealth Centers of Excellence in the country, and the headquarters of the South Carolina Telehealth Alliance.

Treatment for opioid use disorder, whether the patient is pregnant or not, often involves medication-assisted treatment, also known as MAT. It combines medication with counseling. The doctors prescribe drugs such as buprenorphine, which reduces opioid craving, withdrawal and the risk of overdose and talk with the women about what led to their addiction and ways to change their behavior.

Guille said women need to continue treatment for opioid use disorder after their babies are born. "A lot of women will start treatment in pregnancy and do really well. But then in the postpartum period, they are often without insurance and can't afford to continue their treatment and relapse. Drug overdose is one of the leading causes of maternal mortality in the postpartum period."

Sarah encouraged other women struggling with opioid use disorder to get help. "There's still a lot of taboo about it. I think we, a lot of us, feel very guilty, very alone. But look for resources. I know there are Facebook groups for pregnant mothers who are on any type of maintenance program. All of those things are so awesome, and it's important to know - because I didn't know it."

Researchers attempting to improve the treatment for methicillin-resistant Staphylococcus aureus (MRSA) blood infections have discovered the combination of two antibiotics was no better than one, and led to more adverse effects.

MRSA bloodstream infections have a mortality rate between 20 and 25 per cent and cause around 1000 infections a year in Australia.

In what is the biggest trial of MRSA bloodstream infections to date (352 participants from Australia, Singapore, New Zealand and Israel), the CAMERA2 clinical trial, researchers from the Menzies School of Health Research (Menzies) and the Peter Doherty Institute for Infection and Immunity (Doherty Institute) were surprised to see the drug combination wasn't as effective as anticipated.

"The current treatment for MRSA bloodstream infections is an old drug called vancomycin, but it doesn't kill MRSA quickly. So there is an urgent need to find new treatment solutions for this deadly infection," said Professor Joshua Davis from Menzies.

"Many laboratory studies have shown that combining vancomycin with a penicillin-class antibiotic results in improved killing of MRSA."

In this clinical trial involving patients from four countries, half of the participants were randomly allocated to receive vancomycin therapy and the other half received a combination of vancomycin and a penicillin-class antibiotic.

Published today in the journal JAMA, results showed that although the MRSA was killed more quickly, this did not translate to fewer deaths. Surprisingly, combination treatment led to more episodes of kidney injury.

One of the lead researchers, Royal Melbourne Hospital Clinician Researcher at the Doherty Institute, Associate Professor Steven Tong, said this was a significant finding in the future treatment of MRSA infections.

"Clinicians now have the latest evidence as to what works and what doesn't when treating MRSA bloodstream infections, and this trial shows more is not better," Associate Professor Tong said.

This work will now continue with a National Health and Medical Research Council (NHMRC) $5 million grant to conduct the Staphylococcus aureus Network Adaptive Platform trial (SNAP).

"Golden staph is a bacterium that causes over 5000 bloodstream infections a year in Australia, with a mortality rate of 20 per cent, and yet despite these numbers, there is little evidence to guide best management," Associative Professor Tong said.

"This grant brings together a global collaboration to conduct the largest ever clinical trial for Staphylococcus aureus bloodstream infections and address common questions around how to best treat these infections for patients all over the world."

WEST LAFAYETTE, Ind. - One in three adults aged 60 and over suffering from a hip fracture dies within one year. Now, a Purdue University-affiliated startup is moving closer to the start of clinical trials for a novel injectable drug that is targeted to heal broken bones faster and strengthen weak bones.

The Purdue University discovered drug, NOV004, from Novosteo Inc. is unique in that it concentrates at the fracture site while reducing exposure to the rest of the body.

Novosteo, the startup developing the drug, was co-founded by father-son team Philip S. Low, the Presidential Scholar for Drug Discovery and the Ralph C. Corley Distinguished Professor of Chemistry, and Stewart A. Low, the company's CSO and Visiting Scholar in Purdue's Department of Chemistry. The treatment was developed in the Purdue laboratory of Low in the Purdue Institute of Drug Discovery. Currently there are 288 clinical trials performed or in process using Purdue-developed medical treatments at 4,841 sites across the globe.

Scott Salka, who recently joined the startup as executive chair, will use his 28 years of experience as a biotechnology entrepreneur to help Novosteo move its innovations from the laboratory to clinical trials and ultimately in to the hands of doctors and patients.

"We have been working on some amazing science with people truly dedicated to making a difference in reducing the mortality and improving the quality of life for our aging population," said Salka. "We have completed preclinical studies with NOV004 and are looking to take it to clinical trials later this year."

As CEO, Salka has successfully led efforts to advance novel drugs through preclinical and early clinical development, most recently at publicly traded Ampliphi, now Armata NYSE: ARMP. Prior to that he founded and served as CEO for both Ambit Biosciences, acquired by Daiichi Sankyo OTC: DSNKY, and Rakuten Medical.

Novosteo is already looking at the future use of the injectable-targeted drug for other applications, including dental implants, head and facial fractures, and hip and knee replacements. In addition, Novosteo has a pipeline of drugs for treating an array of musculoskeletal maladies. Salka will present some of the technology at Biocom's Global Life Science Partnering Conference this month in La Jolla, California.

Novosteo's technology is licensed through the Purdue Research Foundation Office of Technology Commercialization. The company also received entrepreneurial support from Purdue Foundry, an entrepreneurship and commercialization hub in Discovery Park District's Convergence Center for Innovation and Collaboration where startups, entrepreneurs, innovators and companies can collaborate with Purdue to address global challenges in health, sustainability, IT and space.

The Purdue Institute of Drug Discovery is situated near the district, a $1 billion-plus long-term enterprise to support a transformational center of innovation on the western edge of the Purdue University campus. The district already includes a public airport with a 7,000-foot runway, and partnerships international companies including Rolls-Royce, Schweitzer Engineering Laboratories and Saab. Visit Discovery Park District.

Globally more than 36 million people are living with HIV (PLWH), and a third of them have elevated depressive symptoms. Most PLWH live in developing countries with limited access to mental health services due to HIV-related stigma and a shortage of mental health professionals. Widely accessible smart phones offer a promising intervention delivery mode to address this gap.

Dr. Alicia Hong, Professor at George Mason University's College of Health and Human Services and her colleagues in China developed the digital intervention Run4Love on the popular social media app WeChat. They evaluated Run4Love with a randomized controlled trial (RCT) of 300 PLWH with depression in China, published in the Journal of Medical Internet Research.

Run4Love was a multimedia digital program adapted from evidence-based Cognitive Behavioral Stress Management courses. Participants received stress reduction exercises, cognitive therapy, and exercise guidance on WeChat. Their progress was monitored with timely, tailored feedback. The intervention led to a significant reduction in depressive symptoms (0.6 effect size) in 3-, 6- and 9-month follow-ups and reduced stress, suicidal behaviors, and improved quality of life.

"This is one of the first large RCTs with long-term follow-up to evaluate digital interventions in global health settings." Hong explains, "The success of Run4Love suggests an app-based digital intervention is feasible for many PLWH in resource-limited settings."

The hormone estrogen plays many critical roles in men and women, in both healthy tissues and in cancer. In breast and gynecologic cancers, estrogen sends signals to tumors instructing the cancer cells to grow out of control. In recent years, studies have shed light on the growth-promoting role of estrogen in breast cancer. In endometrial cancer, which arises in the lining of the uterus, estrogen is known to play a critical role in tumor development, yet many insights from how it affects breast cancer do not apply to endometrial cancer. New research, published today in the journal Cancer Research, outlines findings scientists hope will advance our understanding of endometrial cancer and lead to more effective treatments.

"We started out with a question of how estrogen signaling works in endometrial cancer," said Adriana Rodriguez, lead study author. "Most of what we know about estrogen receptor comes from work in breast cancer, although we know that estrogen receptor affects different genes in the two cancer types. In this study, we went looking for which proteins influence estrogen receptor in endometrial cancer cells." Rodriguez is a PhD student at the University of Utah and is a member of the Jay Gertz Laboratory at Huntsman Cancer Institute (HCI) at the University of Utah (U of U).

The researchers discovered that a protein called ETV4 plays a key role in how estrogen communicates with endometrial cancer cells. Estrogen sends pro-growth signals to the cells, and estrogen receptor carries out these signals. The study found that when ETV4 was removed from endometrial cancer cells, estrogen signaling was greatly reduced, subsequently leading to diminished tumor growth. "To our surprise, we found that ETV4 helped to promote estrogen signaling in two ways: first, it was telling estrogen receptor where to bind in the genome; and second, it was causing more estrogen receptor to be active," said Jay Gertz, PhD, a cancer researcher at HCI and assistant professor of oncological sciences at the U of U. Gertz's lab led the study. "If we can find out what is causing ETV4 to be active, then we have a chance of reducing growth-promoting estrogen signaling in uterine tumors."

Gertz's lab used state-of-the-art genomics techniques and collaborated with several research teams with different expertise to expand the study. Using tissue from human tumors growing in mice, the team analyzed ETV4 and estrogen receptor in endometrial cancer.

"Uterine cancer is the most common gynecologic cancer and the fourth most common cancer in Utah women," says Gertz. "Unfortunately, this cancer is on the rise and there are limited treatments for the disease. We believe this study lays the groundwork for future research into ways of blocking estrogen signaling in endometrial cancer."

WASHINGTON, February 11, 2020 -- Acquiring a better understanding for how objects drift in the ocean has importance for a wide range of uses, like tracking algae, predicting the locations of wreckage and debris and better focusing how to clean up ocean litter. Most ways researchers model such movements have largely been put together piece by piece and lack a systematic approach. One new effort looks to provide a clearer alternative.

Researchers have released the results from an experiment aimed at tracking different objects as they drift in the Florida Current, a thermal ocean current that flows from the Straits of Florida around the Florida Peninsula and along the southeastern coast of the United States before joining the Gulf Stream Current near Cape Hatteras. Using satellite data, the group developed a new model for how objects drift based on the results and has been able to keep tabs on four types of custom buoys or drifters for one week.

Lead author Maria Josefina Olascoaga said she and her group are among the first to apply the Maxey-Riley framework to the field of oceanography and see its broad implications for many branches of ocean science. They discuss their work in this week's Physics of Fluids, from AIP Publishing.

"Currently, there are efforts aimed at cleaning up mostly plastic litter in the ocean," said Olascoaga. "The success of those efforts would strongly benefit from our work, as it provides means for effectively designing cleaning strategies by allowing one to better identify the regions within the great garbage patches where litter congregates."

Determining how objects move in a flowing fluid has been notoriously difficult. After nearly a century of research, the Maxey-Riley framework was offered in the 1980s for solving for the fluid flow equation with moving boundaries and has become a major tool in studying particle motion in fluid dynamics.

In December 2017, researchers released cuboidal, spherical, plate-shaped and mat-shaped designed drifters into the waters off the coast of Florida, each about 1 cubic foot large and outfitted with a GPS tracker that pinged satellites every six hours.

The mat-shaped special drifter was designed to mimic the properties of sargassum, a macroalgae that has been implicated in foul odors, water supply discoloration and metal rusting on the shores of the Caribbean.

The group focused on how several variables affected each buoy's inertia over time, including radius, shape, buoyancy and immersion depth. From there, they found that a buoy's buoyancy had the greatest effect on its trajectory in the ocean.

Olascoaga hopes the group's work inspires others to use experimental data to model the world's oceans. The group hopes to further explore the movements of sargassum macroalgae.

KAIST researchers have identified mechanisms that relay prior acquired resistance to the first-line chemotherapy to the second-line targeted therapy, fueling a "domino effect" in cancer drug resistance. Their study featured in the February 7 edition of Science Advances suggests a new strategy for improving the second-line setting of cancer treatment for patients who showed resistance to anti-cancer drugs.

Resistance to cancer drugs is often managed in the clinic by chemotherapy and targeted therapy. Unlike chemotherapy that works by repressing fast-proliferating cells, targeted therapy blocks a single oncogenic pathway to halt tumor growth. In many cases, targeted therapy is engaged as a maintenance therapy or employed in the second-line after front-line chemotherapy.

A team of researchers led by Professor Yoosik Kim from the Department of Chemical and Biomolecular Engineering and the KAIST Institute for Health Science and Technology (KIHST) has discovered an unexpected resistance signature that occurs between chemotherapy and targeted therapy. The team further identified a set of integrated mechanisms that promotes this kind of sequential therapy resistance.

"There have been multiple clinical accounts reflecting that targeted therapies tend to be least successful in patients who have exhausted all standard treatments," said the first author of the paper Mark Borris D. Aldonza. He continued, "These accounts ignited our hypothesis that failed responses to some chemotherapies might speed up the evolution of resistance to other drugs, particularly those with specific targets."

Aldonza and his colleagues extracted large amounts of drug-resistance information from the open-source database the Genomics of Drug Sensitivity in Cancer (GDSC), which contains thousands of drug response data entries from various human cancer cell lines. Their big data analysis revealed that cancer cell lines resistant to chemotherapies classified as anti-mitotic drugs (AMDs), toxins that inhibit overacting cell division, are also resistant to a class of targeted therapies called epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs).

In all of the cancer types analyzed, more than 84 percent of those resistant to AMDs, representatively 'paclitaxel', were also resistant to at least nine EGFR-TKIs. In lung, pancreatic, and breast cancers where paclitaxel is often used as a first-line, standard-of-care regimen, greater than 92 percent showed resistance to EGFR-TKIs. Professor Kim said, "It is surprising to see that such collateral resistance can occur specifically between two chemically different classes of drugs."

To figure out how failed responses to paclitaxel leads to resistance to EGFR-TKIs, the team validated co-resistance signatures that they found in the database by generating and analyzing a subset of slow-doubling, paclitaxel-resistant cancer models called 'persisters'.

The results demonstrated that paclitaxel-resistant cancers remodel their stress response by first becoming more stem cell-like, evolving the ability to self-renew to adapt to more stressful conditions like drug exposures. More surprisingly, when the researchers characterized the metabolic state of the cells, EGFR-TKI persisters derived from paclitaxel-resistant cancer cells showed high dependencies to energy-producing processes such as glycolysis and glutaminolysis.

"We found that, without an energy stimulus like glucose, these cells transform to becoming more senescent, a characteristic of cells that have arrested cell division. However, this senescence is controlled by stem cell factors, which the paclitaxel-resistant cancers use to escape from this arrested state given a favorable condition to re-grow," said Aldonza.

Professor Kim explained, "Before this research, there was no reason to expect that acquiring the cancer stem cell phenotype that dramatically leads to a cascade of changes in cellular states affecting metabolism and cell death is linked with drug-specific sequential resistance between two classes of therapies."

He added, "The expansion of our work to other working models of drug resistance in a much more clinically-relevant setting, perhaps in clinical trials, will take on increasing importance, as sequential treatment strategies will continue to be adapted to various forms of anti-cancer therapy regimens."

New Rochelle, NY, February 11, 2020--A new study evaluated the feasibility and acceptability of using T'ai Chi to improve chronic low back pain in adults over 65 years of age compared to health education and usual care. The results of this randomized controlled trial are published in JACM, the Journal of Alternative and Complementary Medicine, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers, dedicated to paradigm, practice, and policy advancing integrative health. Click here to read this article free on the JACM website through March 11, 2020.

T'ai Chi has been shown effective for improving chronic back pain yet with little attention to older adults. For this study researchers Karen Sherman, PhD and colleagues from Kaiser Permanente Washington Health Research Institute and University of Washington, Seattle, focused only on adults older than 65. They present their study design and findings in the article entitled "T'ai Chi for Chronic Low Back Pain in Older Adults: A Feasibility Trial."

Participants were randomly assigned to 12 weeks of T'ai Chi, a 12-week health education intervention, or usual care. Measures of recruitment and retention contributed to the determination of feasibility. The findings indicate that the study was feasible and had acceptable recruitment, few dropouts, and an excellent safety profile. Among the T'ai Chi participants, 62% attended at least 70% of the classes during the 12-week intervention period. Remarkably, at 52 weeks, 70% of T'ai Chi participants reported having practiced the week before, with a median of 3 days per week and 15 minutes/session. Both participation and perception of helpfulness were lower in the health education group.

"More research is needed on treatments for chronic low back pain in older adults," Dr. Sherman summarizes. "Our study showed that it's feasible to do a clinical trial of T'ai Chi for this condition."

JACM Editor-in-Chief John Weeks, johnweeks-integrator.com, Seattle, WA, states: "Many of us have become familiar with pictures of large groups of older people in China or Hong Kong practicing T'ai Chi together. Dr. Sherman's work suggests that older adults here in the United States may similarly find such practices acceptable and useful."

February 11, 2020 - Laws can have important effects on public health risks and outcomes, while research can provide key evidence to inform effective health-related laws and policies. An introduction to the increasingly influential field of legal epidemiology is presented in a special supplement to the Journal of Public Health Management and Practice (JPHMP). The journal is published in the Lippincott portfolio by Wolters Kluwer.

The supplement is titled Advancing Legal Epidemiology - defined as "the scientific study and deployment of law as a factor in the cause, distribution, and prevention of disease and injury in a population." Assembling nine original research papers and three expert commentaries, the special issue presents "a compelling and diverse body of research that exemplifies how legal epidemiology can help public health practitioners and policy makers recognize opportunities for achieving better health outcomes through law and policy," according to an introduction by Betsy L. Thompson, MD, MSPH, DrPH, Director of the Division for Heart Disease and Stroke Prevention (DHDSP) of the Centers for Disease Control and Prevention (CDC); and supplement Guest Editors Lindsay K. Cloud, JD, and Lance Gable, JD, MPH.

Evaluating the Evidence for Policies on Community Health Workers

A paper by Erika B. Fulmer, MHA, of the DHDSP and colleagues reports on the use of a policy research continuum, including legal epidemiology, to support the development of a community health worker (CHW) workforce. Incorporating CHWs into healthcare teams is a promising strategy to prevent and control cardiovascular disease and type 2 diabetes - particularly in disadvantaged groups such as racial/ethnic minorities, people of lower socioeconomic status, and rural populations. "However, there is limited information examining the impact of state CHW policy interventions," the researchers write.

They applied the DHDSP's policy research continuum, which incorporates legal epidemiology, to CHW workforce development policies. An early-evidence assessment identified policy interventions with a strong evidence base, while policy surveillance provided an overview of the legal landscape supporting such policies. This enabled implementation studies showing how CHW workforce policies were carried out in different states, including qualitative information on early outcomes.

A future policy impact study will examine short- to long-term outcomes, helping to tailor workforce development strategies and maximize the public health benefits of the CHW approach. The DHDSP's policy research continuum "can speed development of tools and resources to enhance decision-making and identify interventions to improve public health impact, use resources wisely, and account for dollars spent," Ms. Fulmer and coauthors write.

Examining the Impact of Pregnancy-Specific Alcohol Policies

A paper by Sarah C.M. Roberts, DrPH, of the University of California, San Francisco and colleagues examines the impact of state-level pregnancy-specific alcohol policies on the health of infants. Using multiple data sources along with original legal research, the analysis included more than 40 years of data with more than 150 million births.

"State-level alcohol pregnancy policy environments have become more punitive over time," the researchers write. However, few studies have examined whether these policies actually improve health. The new study focused on whether health impacts of pregnancy-specific alcohol policies differ among women at different levels of education, as an indicator of socioeconomic status.

The results suggested that pregnancy-specific alcohol policies were more likely to have harmful health effects in women with higher educational status. More than half of policies studied were linked to increased rates of preterm birth and low birth weight for women who had at least a high school education. These included both supportive policies, such as Mandatory Warning Signs; and punitive policies, such as defining alcohol use during pregnancy as child abuse/neglect.

In contrast, policies related to reporting alcohol use during pregnancy - whether or not this information was used for child welfare purposes - were linked to lower rates of adverse birth outcomes among women with less than a high school education. "Public health professionals should take the lead on identifying and developing policy approaches that reduce harms related to alcohol use during pregnancy," Dr. Roberts and coauthors conclude.

WHAT:
In September 2018, the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, issued its Strategic Plan for Tuberculosis Research, which outlined research priorities to reduce and ultimately end the burden of tuberculosis (TB). TB is a bacterial disease that has claimed the lives of more than a billion people in the past two centuries. Now, a new "Perspective" in The Journal of Infectious Diseases by NIAID Director Anthony S. Fauci, M.D., and other Institute officials summarizes recent progress in improved TB diagnostics, therapeutic regimens and prevention approaches that made 2019 a "banner year" for TB research.

Therapeutics trials described by the NIAID authors include BRIEF TB/A5279, a Phase 3 clinical study demonstrating that a one-month course of two antibiotic drugs worked as well as a nine-month regimen of a single drug to prevent TB disease among adults and adolescents with HIV at risk of developing active TB. In June 2019, NIAID and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, also part of NIH, launched the Phase 3 PHOENIx MDR-TB trial in 12 countries. PHOENIx MDR-TB (Protecting Households on Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients) will compare two oral regimens for preventing active TB in adults, teens and children who are at high risk of infection because they live with adults who have multidrug-resistant TB. "Results from this innovative study will inform new TB prevention guidelines to avert the pain, disability and death associated with MDR-TB," Dr. Fauci and his coauthors write.

Advances in TB vaccine development in 2019 included exciting preclinical and clinical results from several studies, the Perspective authors write. A study in macaques, in which the Bacille Calmette-Guerin (BCG) vaccine--the world's only licensed TB vaccine--was administered intravenously (IV) instead of by the standard intradermal route resulted in a dramatic increase in efficacy. The findings support further investigation of IV BCG administration in future human clinical trials. The authors described results of a Phase 2b trial of a candidate TB vaccine M72/AS01 (developed by GlaxoSmithKline) as "groundbreaking." The trial enrolled 3,575 volunteers in three countries and demonstrated 50% efficacy in preventing development of active pulmonary TB compared with placebo.

The challenge in 2020 and beyond is to build on the momentum generated by these recent accomplishments, the authors note. Still urgently needed are rapid, inexpensive and accurate point-of-care diagnostics; new and more effective drugs; and new and improved vaccines that prevent transition from latent infection to active TB disease or that prevent infection altogether. Achieving the end of TB within a generation is possible only through concerted, collective and collaborative efforts that involve government, academia, industry and civil society at all levels, the authors conclude.

Young sexual minority men -- including those who are gay, bisexual, queer or straight-identified men who have sex with men -- do not fully understand their risk for human papillomavirus (HPV) due to a lack of information from health care providers, according to Rutgers researchers.

A Rutgers study published in the Journal of Community Health, examined what young sexual minority men -- a high-risk and high-need population -- know about HPV and the HPV vaccine and how health care providers communicate information about the virus and vaccine.

About 79 million Americans are infected with HPV, with about 14 million becoming newly infected each year, according to the Centers for Disease Control and Prevention. As a sexually transmitted infection, HPV can lead to several types of cancer, including anal and penile cancer, and is particularly concerning for sexual minority men due to the high prevalence of HIV and smoking in this community and the low HPV vaccination rates overall among men.

"Particularly in light of the decades-long focus on gay men's health care as HIV care, there is a missed opportunity for HPV prevention in the community," said study co-author Caleb LoSchiavo, a doctoral student at the Rutgers School of Public Health.

The researchers, who are members of the Rutgers School of Public Heath's Center for Health, Identity, Behavior and Prevention Studies (CHIBPS), analyzed interviews with sexual minority men in their early 20s in New York City and determined they knew little about HPV infection -- including transmission, signs, symptoms and cancer risk -- and vaccination.

They also found that the men did not prioritize HPV vaccination due to the incorrect perception that HPV is an issue that exclusively or primarily affected women.

"Everyone who is sexually active -- regardless of gender, sexual orientation, partners' genders, relationship or marital status -- should talk to their doctor about receiving the HPV vaccine to prevent a future generation who may develop HPV-related cancers, such as cervical, oral and anal cancer, as we have seen emerging in Baby Boomers and Gen-Xer s," said Perry N. Halkitis, Rutgers School of Public Health dean, CHIBPS director, and PI of the study.

The U.S. Food and Drug Administration has expanded the use of HPV vaccine to people between the ages of 27 to 45. Originally, it was prescribed for those between the ages of 9 to 26.

In the study, researchers found that health care providers rarely discuss HPV and the HPV vaccine with patients who are young sexual minority men, and when they do, their communication is often inadequate in conveying potential risks of HPV and benefits of vaccination.

"Clinicians have a direct role in expanding the availability of LGBTQ-competent healthcare," said lead author Jessica Jaiswal, an assistant professor at the University of Alabama, and CHIBPS affiliate. "By learning about sexual minority men's diverse health needs and routinely offering the HPV vaccine, we can move toward a health promotion model and not only a disease prevention model."

CHICAGO --- The majority of teenage boys most at risk for developing HIV are not being tested for the disease, reports a new Northwestern Medicine study. This lack of testing feeds the growing epidemic of undiagnosed HIV infections in the United States.

An estimated 14.5% of HIV infections in the U.S. are undiagnosed, but among 13- to 24-year-olds, the undiagnosed rate is more than 3.5 times greater (51.4%).

The study found:

Fewer than one in four gay, bisexual and questioning teenage boys (under 18 years old) has ever received an HIV test in their lifetime

Among teens engaging in condomless anal sex, only one in three report testing for HIV, despite the high risk of transmission

This group of boys is disproportionately at risk to acquire HIV but faces many structural barriers that hinder testing, such as simply not knowing they can legally consent to getting an HIV test, where to get tested and fears of being outed. This is true even for those who want to check their status, the study found. This new study identified factors that increase the likelihood of testing, including parents talking about sex and HIV prevention, knowing basic facts about HIV, and feeling that testing is important and they are empowered to do it.

When all these factors were considered together, the most important factors were having had conversations with their doctors about HIV, same-sex behavior and sexual orientation.

"Doctors - pediatricians in particular - need to be having more frank and open conversations with their male teenage patients, including a detailed sexual history and a discussion about sexual orientation - ideally a private conversation without parents present," said first and senior author Brian Mustanski, director of the Institute for Sexual and Gender Minority Health and Wellbeing (ISGMH) at Northwestern University Feinberg School of Medicine. "If parents ask their teen's provider to talk about sexual health and testing, this may be enough to start that key dialogue in the exam room, leading to an HIV test."

The findings will be published February 11 in the journal Pediatrics.

This news comes in the wake of President Donald Trump's announcement of the 2019 federal "Ending the HIV epidemic" initiative. One of the four pillars of the initiative is diagnosing individuals with HIV early after infection. But in order to diagnose patients, individuals must be tested for HIV, Mustanksi said.

The following simple changes within the pediatric practice can facilitate important discussions that could improve testing among gay, bisexual and questioning teenagers, Mustanski said:

Pediatricians can update their intake forms to include a section on sexual orientation

By hanging visual cues like Safe Zone or LGBTQ ally posters in exam rooms, they can signal safety and acceptance to adolescents

Doctors can articulate to patients that their office is a safe-space to discuss sexuality

They can reinforce doctor-patient confidentiality, which can be accomplished by asking patients' parents to exit the room during part of the patient-history

For pediatricians who do not want to engage in conversations about sexual orientation, defaulting to HIV testing with informed "opt-out" can be effective, too. Teens also can opt to get testing in many community organizations that offer HIV testing. A map of these clinics can be found at locator.hiv.gov. These programs are equipped to help counsel people on how to reduce their future risk for HIV and how to access health care services if they test positive.

"To promote these options, we need health education programs that teach teens about their legal rights to testing, the importance of testing and how to go about it," said co-author Kathryn Macapagal, research assistant professor of medical social sciences and psychiatry and behavioral sciences at Feinberg. "Our team developed a program that addresses these needs for teens, and we expect the results of our nationwide trial to come out soon."

As part of a larger randomized control trial, the study asked 699 gay, bisexual and questioning male teenagers (ages 13-18) about their lifetime receipt of an HIV test, demographics, sexual behaviors and condom use, experience of HIV education from schools and family, sexual health communication with doctors, HIV knowledge, and prevention/risk attitudes.