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Newswise — ANN ARBOR, MI – An emergency room visit for an illness or injury may seem like a strange time to try to motivate someone to cut back on using drugs. But a new study suggests that even a half-hour chat with a trained counselor, or a few minutes using a special tablet computer program with a “virtual therapist”, can turn an emergency room trip into the basis for a long-lasting drop in a person’s use of illegal drugs or misuse of prescription medicines. The findings, from a carefully designed randomized controlled trial involving 780 people at a Flint, Michigan ER who indicated recent drug use on a health survey, suggest that ER visits might serve as effective ‘teachable moments’ for drug use. Published in the journal Addiction by a team from the University of Michigan Addiction Center and Institute for Healthcare Policy and Innovation, the study looks at the impact of a drug-related brief intervention based on a technique called motivational interviewing. The study randomly assigned two-thirds of the participants to an intervention aimed at motivating them to set goals for cutting back on their substance use, on their own or with help. Then, the researchers followed up with all participants three times in the year after their ER visit – including urine tests to check the accuracy of participants’ statements about their drug use. Those who talked with a therapist, who used the tablet program to guide the discussion, reported significantly fewer days of drug use in the year after the ER visit -- about 21 percent less -- and fewer days on which they used multiple drugs. And even those who didn’t talk with a therapist, but interacted with a virtual therapist on a computer program on their own, had 16 percent fewer days of marijuana use a year later. Though other studies have cast doubt on the effectiveness of this approach for reducing drug use, study leader Frederic Blow, Ph.D., director of the U-M Addiction Center, says the new findings come from a trial that was carefully planned and conducted, with high follow-up rates. “Our results show that this approach can work if it’s done well, and that the perception that people won’t change their use based on motivational approaches is nonsense,” says Blow. “The findings especially support engaging computer-based aids that help therapists deliver this brief intervention in a way that tailors it to the individual patient, and works with them to make a plan for reducing their substance use.” Blow is a professor of psychiatry at the U-M Medical School’s Department of Psychiatry, and a research scientist at the Center for Clinical Management Research at the Ann Arbor Department of Veterans Affairs (VA) Healthcare System. Blow and his colleagues worked with a technology firm to create the tablet interface called HealthiER You, using a grant from the National Institute on Drug Abuse. They recruited participants in the ER of Hurley Medical Center, which partners with U-M’s academic medical center Michigan Medicine to provide emergency care. Most of the study participants were low-income adults their 30s – a demographic group that has high rates of substance use, and may be less likely to access other healthcare services outside the ER. The study did not include people with certain psychiatric conditions or those seeking care for suicidal thinking or sexual assault. “An ER visit is a time that may prompt people to think about their lives, and be more receptive to thinking about their drug use,” says Blow. “This is not about going cold turkey, but about setting goals to reduce or stop use for health reasons.” He notes that previous research has already shown that motivational interviewing in the ER can help people reduce their alcohol use, and that previous studies to use it for substance use have yielded mixed or negative results. But the new study used random selection to find participants across all 24 hours of the day, and excluded people who inject drugs. It also tailored the program interface to the answers that participants gave on questionnaires. Screen shots of the program are available in the paper. The control group also showed a modest drop in drug use, most likely because they were asked about their use of drugs in the ER and at each follow-up. This could also be true of the intervention groups. Nonetheless, there was a significant drop in drug use by members of the groups that received the active interventions, compared to the control group. Blow and his colleagues hope that further research will put their results to the test. Because their study showed that follow-up interventions by therapists three months after the ER visit did not have a measurable effect, they also hope to study the impact of peer support, text messages, and other tools in the post-ER timeframe. “We believe interventions like these can work in a range of populations, if we deliver them in a motivational way that figures out the best options for each person and supports them with electronic or personal contact that forms a real connection over time,” says Blow. In addition to Blow and senior author Kristen L. Barry, Ph.D., the study’s authors are U-M’s Maureen A. Walton, M.P.H., Ph.D., Amy S.B. Bohnert, Ph.D., Rosalinda V. Ignacio, M.S., Stephen Chermack, Ph.D., Mark Ilgen, Ph.D.; Rebecca M. Cunningham, M.D. (from Emergency Medicine), and Brenda M. Booth, Ph.D. of the University of Arkansas for Medical Science and VA Center for Mental Healthcare Outcomes and Research. Drs. Blow, Barry, Walton, Bohnert, Cunningham, and Ilgen are members of the Institute for Healthcare Policy and Innovation (IHPI). All but Barry are also members of the U-M Injury Center, which Cunningham directs. Blow, Bohnert, and Ilgen are members of the VA Center for Clinical Management Research. The study was funded by grant DA026029. Reference: Addiction, Early View, DOI: 10.1111/add.13773 http://onlinelibrary.wiley.com/doi/10.1111/add.13773/pdf SEE ORIGINAL STUDY    

Newswise — BIRMINGHAM, Ala. – Failure of hormone deprivation therapy, which is used to slow prostate cancer in patients, leads to castration-resistant prostate cancer, a lethal form of advanced disease with limited treatment options. University of Alabama at Birmingham researchers have discovered that endostatin, a naturally occurring protein in humans, can significantly decrease proliferation of castration-resistant prostate cells in culture, and in a recent paper in The FASEB Journal, they describe the physiological pathways and signaling evoked by endostatin. This endostatin effect is now being tested in a preclinical xenograft animal model of castration-resistant prostate cancer. “We hope we can delay the onset of castration-resistant disease,” said Selvarangan Ponnazhagen, Ph.D., a UAB professor in the UAB Department of Pathology who holds an Endowed Professorship in Experimental Cancer Therapeutics at UAB. The medical treatment that deprives prostate cancer cells of androgen hormones through anti-hormone therapy creates oxidative stress in those cancer cells. This oxidative stress is associated with reactivated signaling by the androgen receptor in the cells, causing resistance to the anti-hormone therapy. The UAB researchers, led by Ponnazhagen and first author Joo Hyoung Lee, Ph.D., hypothesized that the oxidative stress might be triggered upstream of the androgen receptor, with the glucocorticoid receptor as the stress-inducer. If so, endostatin might interact with the glucocorticoid receptor to remove the oxidative stress and reduce that pro-tumorigenic function in the cancer cells, thereby preventing or delaying the onset of castration-resistant disease. They found that endostatin did target the androgen and glucocorticoid receptors through reciprocal regulation that affected downstream pro-oxidant signaling mechanisms. The effect of endostatin treatment, possibly mediated through direct interaction of endostatin with both androgen receptor and glucocorticoid receptor, downregulated both the steroid hormone receptor levels and led to physiological changes that removed oxidative stress from the cancer cells. Treatment with endostatin resulted in a significant up-regulation of the major cellular machinery to scavenge destructive reactive-oxygen-species, including manganese superoxide dismutase, the glutathione system and the biliverdin/bilirubin redox cycle. Increased levels of reduced glutathione, a major internal antioxidant molecule, was accompanied by increased glucose uptake as the endostatin-treated cancer cells appeared to shift their metabolism to the pentose phosphate pathway. This pathway uses glucose to maintain the antioxidant system, which includes NAD/NADP production and glutathione. “Our study suggests that the potential therapeutic application of endostatin may include combination with the frontline androgen-deprivation therapy that targets prostate cancer at early stages,” the researchers wrote. “Based on the known anti-angiogenic properties of endostatin and on more interesting evidence that human prostate endothelial cells also express androgen receptor, the application of endostatin in combination therapies could synergize tumoristatic and tumoricidal effects with minimal resistance.” Besides Ponnazhagen and Lee, authors of the paper, “Endostatin inhibits androgen-independent prostate cancer growth by suppressing nuclear receptor-mediated oxidative stress,” are Minsung Kang and W. Timothy Garvey, UAB Department of Nutrition Sciences; Hong Wang and Victor M. Darley-Usmar, UAB Department of Pathology; Gurudatta Naik and Guru Sonpavde, UAB Comprehensive Cancer Center; and James A. Mobley, UAB Department of Surgery. Garvey also serves in the Birmingham Veterans Affairs Medical Center, and Lee is a research associate in pathology.

Newswise — BLOOMINGTON, Ind. -- A study by Indiana University researchers has identified 24 compounds -- including caffeine -- with the potential to boost an enzyme in the brain shown to protect against dementia. The protective effect of the enzyme, called NMNAT2, was discovered last year through research conducted at IU Bloomington. The new study appears today in the journal Scientific Reports. "This work could help advance efforts to develop drugs that increase levels of this enzyme in the brain, creating a chemical 'blockade' against the debilitating effects of neurodegenerative disorders," said Hui-Chen Lu, who led the study. Lu is a Gill Professor in the Linda and Jack Gill Center for Biomolecular Science and the Department of Psychological and Brain Sciences, a part of the IU Bloomington College of Arts and Sciences. Previously, Lu and colleagues found that NMNAT2 plays two roles in the brain: a protective function to guard neurons from stress and a “chaperone function” to combat misfolded proteins called tau, which accumulate in the brain as "plaques" due to aging. The study was the first to reveal the "chaperone function" in the enzyme. Misfolded proteins have been linked to neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, as well as amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease. Alzheimer’s disease, the most common form of these disorders, affects over 5.4 million Americans, with numbers expected to rise as populations age. To identify substances with the potential to affect the production of the NMNAT2 enzyme in the brain, Lu’s team screened over 1,280 compounds, including existing drugs, using a method developed in her lab. A total of 24 compounds were identified as having potential to increase the production of NMNAT2 in the brain. One of the substances shown to increase production of the enzyme was caffeine, which also has been shown to improve memory function in mice genetically modified to produce high levels of misfolded tau proteins. Lu's earlier research found that mice altered to produce misfolded tau also produced lower levels of NMNAT2. To confirm the effect of caffeine, IU researchers administered caffeine to mice modified to produce lower levels of NMNAT2. As a result, the mice began to produce the same levels of the enzyme as normal mice. Another compound found to strongly boost NMNAT2 production in the brain was rolipram, an "orphaned drug" whose development as an antidepressant was discontinued in the mid-1990s. The compound remains of interest to brain researchers due to several other studies also showing evidence it could reduce the impact of tangled proteins in the brain. Other compounds shown by the study to increase the production of NMNAT2 in the brain -- although not as strongly as caffeine or rolipram -- were ziprasidone, cantharidin, wortmannin and retinoic acid. The effect of retinoic acid could be significant since the compound derives from vitamin A, Lu said. An additional 13 compounds were identified as having potential to lower the production of NMNAT2. Lu said these compounds are also important because understanding their role in the body could lead to new insights into how they may contribute to dementia. "Increasing our knowledge about the pathways in the brain that appear to naturally cause the decline of this necessary protein is equally as important as identifying compounds that could play a role in future treatment of these debilitating mental disorders," she said. Other researchers on the study were assistant research scientist Yousuf O. Ali and graduate student Gillian Bradley, both of the Linda and Jack Gill Center for Biomolecular Science at IU Bloomington. Ali and Lu are co-corresponding authors on the paper. This study was funded by the National Institutes of Health's National Institute of Neurological Disorders and Stroke and the Belfer Family Foundation. SEE ORIGINAL STUDY

Newswise — T cells, the managers of our immune systems, spend their days shaking hands with another type of cell that presents small pieces of protein from pathogens or cancerous cells to the T cell. But each T cell is programmed to recognize just a few protein pieces, known as antigens, meaning years can go by without the T cell, or its descendants, recognizing an antigen. When the T cell does recognize an antigen, it gives the cell presenting the antigen a “hug,” so to speak, instead of a handshake. This initial interaction causes the T cell to search nearby to find other cells that are presenting the same antigen to give them “hugs” as well. In a study published today in Science Signaling, UCLA researchers have discovered that after the initial hug, T cells become more gregarious, giving something more like a bear hug to any cell presenting its antigen. These larger hugs help to activate the T cell, equipping it to go out into the body and coordinate multi-cellular attacks to fight infections or cancers. The UCLA team learned that how stiff or soft T cells are controls their response — the cells react slowly when they are stiff and trigger easily when they are soft. “T cells are like the shy person at the office holiday party who acts stiff until they loosen up a bit and then are all over the dance floor,” said Dr. Manish Butte, associate professor of pediatrics and microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA and the study’s senior author. Butte and his colleagues pioneered an approach using an instrument called an atomic-force microscope to make real-time observations about what excites T cells at the nanoscale. Once they learned that T cells soften after activation, the UCLA team identified the biochemical pathway that controls the cell’s stiffness. They then identified drugs that can help the T cells either elicit or subdue a response. The finding provides scientists with a new capability to manipulate the immune system, Butte said. Diseases arise in people and animals when T cells attack the body’s other cells, or when they fail to signal attacks against cancer cells or infectious pathogens. “Until now, we had a limited understanding of what controls T cell activation,” said Butte, who is chief of pediatric allergy and immunology at Mattel Children’s Hospital UCLA and a member of the UCLA Children’s Discovery and Innovation Institute. “We wanted to identify how to both encourage and speed up T cell activation for fighting infections and cancers and to disrupt it in order to prevent immune disease. Now that we understand the precise steps taking place, our findings suggest that altering T cell stiffness with drugs could one day help us thwart diseases where T cells are too active or not active enough.” Butte and colleagues are beginning to apply these findings — in a study funded by the National Institutes of Health — to diminish the role T cells play in triggering Type 1 diabetes. “We can’t talk about precision medicine and still use a sledgehammer to treat disease,” Butte said. “By exploiting the mechanism we discovered to soften T cells, we could accelerate vaccine responses so a patient won’t need multiple boosters and months of waiting to get full immunity. Or we could stiffen up T cells to prevent the body from rejecting transplanted organs.” Grants from the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, the Stanford Child Health Research Institute, the Morgridge Family Foundation and the National Science Foundation supported the research.

Newswise — DALLAS –  Could lung cancer be hiding in kidney cancer patients? Researchers with the Harold C. Simmons Comprehensive Cancer Center’s Kidney Cancer Program studied patients with metastatic kidney cancer to the lungs and found that 3.5 percent of the group had a primary lung cancer tumor that had gone undiagnosed. This distinction can affect treatment choices and rates of survival. “Kidney cancer spreads primarily to the lungs making the detection of a primary lung cancer difficult. Lung cancer is typically more aggressive than kidney cancer. Undetected, lung cancer may spread and eventually kill the patient,” said Dr. James Brugarolas, Director of the Kidney Cancer Program and Associate Professor of Internal Medicine at UT Southwestern Medical Center. Mel Moffitt, an Army veteran who survived serving in Vietnam, is among those now fighting both lung cancer and kidney cancer. Mr. Moffitt, 70, was initially diagnosed with kidney cancer in 2008, leading to removal of one of his kidneys. By 2012, the cancer had spread to his lungs and lymph nodes. Before coming to UT Southwestern, he had been told he had less than a year to live. In 2015, a new primary tumor was found in his lung. “It was like we turned around, and the cancer said ‘By the way, I’m over here too,’” said his wife of 47 years, Kennon Moffitt, whom he met at the officer’s club in El Paso before shipping off to Vietnam. “I will keep fighting,” pledged Mr. Moffitt, who has been through molecularly targeted drug therapy, stereotactic radiotherapy, and is combating his latest lung and kidney cancer diagnosis with immunotherapy and chemotherapy treatment. Still, he said, he is grateful to have survived so many years since his initial diagnosis, years that included the birth of his three grandchildren, now ages 8, 6 and 4, and the chance to restore a 1969 red Corvette, which the couple plans to drive in a Fourth of July parade this summer. Watch Mr. Moffitt’s story. Nearly 400,000 Americans are now living with a diagnosis of kidney cancer and more than 60,000 people are expected to be diagnosed with kidney cancer this year, according to the National Cancer Institute (NCI). Five-year survival rate averages range from more than 80 percent for stage 1, when cancer is contained in the kidney, to about 53 percent for stage 3, when it has spread beyond the kidney, to just 8 percent for stage 4, when the cancer spreads to more distant parts of the body or other organs. Texas has the fifth-highest rate of this cancer in the U.S. and it is the fourth most common cancer treated at the Simmons Comprehensive Cancer Center, where survival rates for patients with stage 4 kidney cancer are double national benchmarks, noted Dr. Brugarolas, a Virginia Murchison Linthicum Scholar in Medical Research at UT Southwestern. In this retrospective study of 151 patients at the Simmons Comprehensive Cancer Center, investigators identified 85 people who had kidney cancer metastasized to the lungs, and three who had a primary lung cancer. Investigators found only four previous cases described in the literature, leading them to suspect the incidence of lung cancers in kidney cancer patients may be underreported. Because UT Southwestern is a tertiary care referral center, investigators noted that rates could be different in the general population. Up to 6 percent of patients with metastatic kidney cancer also may have a lung cancer, investigators noted in the study, published in Clinical Genitourinary Cancer. “Our report raises an important flag for medical oncologists and radiologists to be on the lookout for a hidden lung cancer,” said Dr. Brugarolas. The study was supported by a SPORE (Specialized Program of Research Excellence) award from the NCI, only the second such award for kidney cancer in the nation. The SPORE investigators are working to better understand how kidney cancer develops and spreads, as well as to develop new therapies targeting adult and pediatric kidney cancer. UT Southwestern also leads a 20-year, multi-institutional SPORE grant in lung cancer that is the largest thoracic oncology effort in the U.S. UT Southwestern researchers involved in the current study included Dr. Ivan Pedrosa, Chief of Magnetic Resonance Imaging (MRI), Associate Professor of Radiology and of the Advanced Imaging Research Center, and a Co-Leader of the Kidney Cancer Program, who holds the Jack Reynolds, M.D., Chair in Radiology; Dr. Payal Kapur, Associate Professor of Pathology and Urology; and Dr. Isaac Bowman, a hematology-oncology fellow, who is first author on the study. UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center is the only NCI-designated Comprehensive Cancer Center in North Texas and one of just 47 NCI-designated Comprehensive Cancer Centers in the nation. Simmons Comprehensive Cancer Center includes 13 major cancer care programs, and its education and training programs support and develop the next generation of cancer researchers and clinicians. Simmons Comprehensive Cancer Center is among only 30 U.S. cancer research centers to be designated by the NCI as a National Clinical Trials Network Lead Academic Participating Site.   About UT Southwestern Medical Center UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year.   ###

Newswise — Anaheim, CA.  HumanN is pleased to announce the launching of Protein40®, a powerful functional foods supplement that delivers three high quality proteins – in one convenient shake for seven full hours of muscle and bone support during the Natural Products Expo West trade show. HumanN has partnered with Dr. John Ivy, Ph.D., one of the world’s renowned experts in protein timing, nutrition, and exercise performance to create Protein40. Dr. Ivy is the bestselling author of Nutrient Timing: The Future of Sports Nutrition, and serves as the Executive Director of Sports Nutrition Research for HumanN, leading its science team in developing this groundbreaking product for anyone over the age of 40. “Most people over the age of 35 do not realize that essential hormones associated with a reduction in strength, power and speed of movement to peak exercise begin to naturally decline,” Dr. Ivy shares. “By age 40, you need twice as much protein to simply maintain existing muscle mass, especially as your body’s ability to synthesize protein drops. Most notably, Protein40 has been formulated to help the body aid in muscle recovery and support bone mass.” Protein40 delivers 20 grams of premium proteins (Whey Protein Isolate, Calcium Caseinate, Micellar Casein) that are digested at different rates for seven continuous hours of support to help address any protein gaps in diet and lifestyle. These proteins are then combined with essential nutrients to maximize and prolong protein synthesis, including 4g of leucine, a branch amino acid that enhances protein synthesis. Protein40 also provides 50 percent of the recommended daily allowance for magnesium and 30 percent of calcium. Available in a chocolate flavor, Protein40 features a low glycemic index, contains no artificial sweeteners of flavors, and has only 140 calories per serving “The biggest mistake I see those seeking [to build] muscle make,” according to Registered Dietician Mari-Etta Parrish, “is to disregard their need to trigger insulin in order to build muscle. In other words, they mistakenly prioritize only protein… and don't realize that a certain amount of sugar or carbohydrate is also necessary to really optimize the muscle maintenance or building process. Not only does [Protein40] contain a balanced combination of highly bio-available proteins, it includes necessary carbohydrate and helpful minerals.” “We developed Protein40 based on well-established scientific principal to provide an optimal blend of proteins for enhanced muscle and bone performance and recovery,” Dr. Ivy adds. “Whey isolate is a quickly absorbed fast acting protein. It stimulates muscle protein synthesis within 30 minutes of consumption. Micellar casein is slowly digested and the absorption of its component amino acids is slow. While protein synthesis is slow to respond to micellar casein, its effect is prolonged. It is also the only protein that has been shown to help reduce muscle protein breakdown as well as stimulate muscle protein synthesis. Calcium caseinate’s digestion rate is slower than whey isolate, but faster than micellar casein, and therefore its effect on protein synthesis is intermediate to whey isolate and micellar casein. In addition, calcium caseinate provides calcium for bone health. The amount of protein is important. HumanN Protein40 provides 20 grams of protein per serving, which is enriched with an additional 2 grams of the branched chain amino acid, L-leucine. Because of the quality of protein used, there are 11.0 g of essential amino acids in each serving and 4.0 g of L-leucine. The ability of a protein supplement to stimulate protein synthesis is closely related to the amount of L-leucine and essential amino acids delivered in the supplement. L-leucine is the key activator of protein synthesis, while the other essential amino acids facilitates the activity of L-leucine. This level of L-leucine and essential amino acids has been found to maximally stimulate muscle protein synthesis. EDITOR’S NOTE: Dr. Ivy is available for interviews upon request. HumanN is exhibiting and conducting product sampling at Expo West in booth 1972. Dr. John Ivy is the Teresa Lozano Long Endowed Chair Emeritus at the University of Texas at Austin. He received his Ph.D. in Exercise Physiology from the University of Maryland, and trained in physiology and metabolism at Washington University School of Medicine as an NIH Post-Doctoral Fellow. He served on the faculty at the University of Texas for 31 years and as Chair of the Department of Kinesiology and Health Education for 13 years. Formerly Neogenis Laboratories, HumanN is the only company in the world licensed to use this patented Nitric Oxide platform technology. Powered by a blue ribbon panel Scientific Advisory Board that includes Dr. Nathan Bryan and Dr. John Ivy, HumanN believes in helping every human reach their full potential across every phase of life. As a University of Texas Austin technology portfolio company, HumanN upholds extremely high standards in the production of its line of functional foods and supplements, including conducting human clinical trials to support the safety and efficacy of its products. In 2016, HumanN was named to the Inc. 5000 List for the second straight year, and has been featured in The Wall Street Journal, The Los Angeles Times, Men’s Journal, and more.

Newswise — BOSTON — An epidemiological analysis of data from more than 6,000 American and Canadian women with breast cancer finds that post-diagnosis consumption of foods containing isoflavones—estrogen-like compounds primarily found in soy food—is associated with a 21 percent decrease in all-cause mortality. This decrease was seen only in women with hormone-receptor-negative tumors, and in women who were not treated with endocrine therapy such as tamoxifen. The study, led by nutrition and cancer epidemiologist Fang Fang Zhang, M.D., Ph.D., from the Friedman School of Nutrition Science and Policy at Tufts University, was published March 6 in Cancer. “At the population level, we see an association between isoflavone consumption and reduced risk of death in certain groups of women with breast cancer. Our results suggest, in specific circumstances, there may be a potential benefit to eating more soy foods as part of an overall healthy diet and lifestyle,” said Zhang, who is also the 2016-2017 Miriam E. Nelson Tisch Faculty Fellow at the Jonathan M. Tisch College of Civic Life and an adjunct scientist in nutritional epidemiology at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts. “Since we only examined naturally occurring dietary isoflavone, we do not know the effect of isoflavone from supplements. We recommend that readers keep in mind that soy foods can potentially have an impact, but only as a component of an overall healthy diet,” she adds. Isoflavones have been shown to slow the growth of breast cancer cells in laboratory studies, and epidemiological analyses in East Asian women with breast cancer found links between higher isoflavone intake and reduced mortality. However, other research has suggested that the estrogen-like effects of isoflavones may reduce the effectiveness of endocrine therapies used to treat breast cancer. Because of this double effect, it remains unknown whether isoflavone consumption should be encouraged or avoided by breast cancer patients. In the current study, Zhang and her colleagues, including Esther John, Ph.D., senior cancer epidemiologist at the Cancer Prevention Institute of California, analyzed data on 6,235 American and Canadian breast cancer patients from the Breast Cancer Family Registry, a National Cancer Institute-funded program that has collected clinical and questionnaire data on enrolled participants and their families since 1995. Women were sorted into four quartile groups based on the amount of isoflavone they were estimated to have consumed, calculated from self-reported food frequency questionnaires. Mortality was examined after a median follow-up of 9.4 years. The team found a 21 percent decrease in all-cause mortality among women in the highest quartile of intake, when compared to those in the lowest quartile. The association between isoflavone intake and reduced mortality was strongest in women with tumors that lacked estrogen and progesterone receptors. Women who did not receive endocrine therapy as a treatment for their breast cancer had a weaker, but still significant association. No associations were found for women with hormone-receptor-positive tumors and for women who received endocrine therapy. While the study categorized women in the highest quartile as those who consumed 1.5 milligrams or more of isoflavone per day—equivalent to a few dried soybeans—the authors caution that individuals tend to underestimate their food intake when filling out questionnaires. “The comparisons between high and low consumption in our study are valid, but our findings should not be interpreted as a prescription,” Zhang said. “However, based on our results, we do not see a detrimental effect of soy intake among women who were treated with endocrine therapy, which has been hypothesized to be a concern. Especially for women with hormone-receptor-negative breast cancer, soy food products may potentially have a beneficial effect and increase survival.” The large size and diverse racial/ethnic makeup of the Breast Cancer Family Registry allowed the researchers to evaluate mortality risk across different subtypes of breast cancer and subgroups of patients, and adjust for confounding factors. However, the authors note that dietary isoflavone intake was correlated with socioeconomic and lifestyle factors, which may also play a role in lowering mortality. In particular, women who consumed higher levels of dietary isoflavone were more likely to be Asian Americans, young, physically active, more educated, not overweight, never smokers, and drink no alcohol. Although the team controlled for these factors in the analyses, the possibility of a partial confounding effect on the associations identified in the study cannot be ruled out. “Whether lifestyle factors can improve survival after diagnosis is an important question for women diagnosed with hormone-receptor negative breast cancer, a more aggressive type of breast cancer. Our findings suggest that survival may be better in patients with a higher consumption of isoflavones from soy food,” John said. Additional authors on this study are Danielle E. Haslam, nutritional epidemiology doctoral candidate at the Friedman School of Nutrition Science and Policy at Tufts University, Mary Beth Terry, Ph.D., professor of epidemiology at Mailman School of Public Health at Columbia University, Julia A. Knight, Ph.D., professor of epidemiology at the Dalla Lana School of Public Health at the University of Toronto and senior investigator at the Lunenfeld-Tanenbaum Research Institute, Sinai Health System in Toronto, Irene L. Andrulis, Ph.D., professor of molecular genetics at the Dalla Lana School of Public Health at the University of Toronto and senior investigator at the Lunenfeld-Tanenbaum Research Institute, Sinai Health System in Toronto, Mary Daly, M.D., Ph.D., chair and professor in the department of clinical genetics and director of risk assessment program at the Fox Chase Cancer Center in Philadelphia, Saundra S. Buys, M.D., medical director of Huntsman Cancer Institute's high risk breast cancer clinic and a professor in the department of medicine at the University of Utah School of Medicine. This work was supported by an award from National Cancer Institute of the National Institutes of Health (CA164920). Zhang, F. F., Haslam, D. E., Terry, M. B., Knight, J.A., Andrulis, I. L., Daly, M., Buys, S.S., and John, E. M. (2017). Dietary isoflavone intake and all-cause mortality in breast cancer survivors: the Breast Cancer Family Registry. Cancer. Published online: March 6, 2017. DOI: 10.1002/cncr.30615. URL upon publication: http://doi.wiley.com/10.1002/cncr.30615 About the Friedman School of Nutrition Science and Policy at Tufts University The Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts University is the only independent school of nutrition in the United States. The school’s eight degree programs – which focus on questions relating to nutrition and chronic diseases, molecular nutrition, agriculture and sustainability, food security, humanitarian assistance, public health nutrition, and food policy and economics – are renowned for the application of scientific research to national and international policy. ###

Newswise — CHAPEL HILL, NC – A national research network led by UNC School of Medicine’s Joseph Piven, MD, found that many toddlers diagnosed with autism at two years of age had a substantially greater amount of extra-axial cerebrospinal fluid (CSF) at six and 12 months of age, before diagnosis is possible. They also found that the more CSF at six months – as measured through MRIs – the more severe the autism symptoms were at two years of age. “The CSF is easy to see on standard MRIs and points to a potential biomarker of autism before symptoms appear years later,” said Piven, co-senior author of the study, the Thomas E. Castelloe Distinguished Professor of Psychiatry, and director of the Carolina Institute for Developmental Disabilities (CIDD). “We also think this finding provides a potential therapeutic target for a subset of people with autism.” The findings, published in Biological Psychiatry, point to faulty CSF flow as one of the possible causes of autism for a large subset of people. “We know that CSF is very important for brain health, and our data suggest that in this large subset of kids, the fluid is not flowing properly,” said Mark Shen, PhD, CIDD postdoctoral fellow and first author of the study. “We don’t expect there’s a single mechanism that explains the cause of the condition for every child. But we think improper CSF flow could be one important mechanism.” Until the last decade, the scientific and medical communities viewed CSF as merely a protective layer of fluid between the brain and skull, not necessarily important for proper brain development and behavioral health. But scientists then discovered that CSF acted as a crucial filtration system for byproducts of brain metabolism. Every day, brain cells communicate with each other. These communications cause brain cells to continuously secrete byproducts, such as inflammatory proteins that must be filtered out several times a day. The CSF handles this, and then it is replenished with fresh CSF four times a day in babies and adults. In 2013, Shen co-led a study of CSF in infants at UC Davis, where he worked with David Amaral, PhD, co-senior author of the current Biological Psychiatry study. Using MRIs, they found substantially greater volumes of CSF in babies that went on to develop autism. But they cautioned the study was small – it included 55 babies, 10 of whom developed autism later – and so it needed to be replicated in a larger study of infants. When he came to UNC, Shen teamed up with Piven and colleagues of the Infant Brain Imaging Study (IBIS), a network of autism clinical assessment sites at UNC, the University of Pennsylvania, Washington University in St. Louis, and the University of Washington. In this most recent study of CSF, the researchers enrolled 343 infants, 221 of which were at high risk of developing autism due to having an older sibling with the condition. Forty-seven of these infants were diagnosed with autism at 24 months, and their infant brain MRIs were compared to MRIs of other infants who were not diagnosed with autism at 24 months of age. The six-month olds who went on to develop autism had 18 percent more CSF than six-month olds who did not develop autism. The amount of CSF remained elevated at 12 and 24 months. Infants who developed the most severe autism symptoms had an even greater amount of CSF – 24 percent greater at six months. Also, the greater amounts of CSF at six months were associated with poorer gross motor skills, such as head and limb control. “Normally, autism is diagnosed when the child is two or three years old and beginning to show behavioral symptoms; there are currently no early biological markers,” said David G. Amaral, director of research at the UC Davis MIND Institute. “That there’s an alteration in the distribution of cerebrospinal fluid that we can see on MRIs as early as six months, is a major finding.” The researchers found that increased CSF predicted with nearly 70 percent accuracy which babies would later be diagnosed with autism. It is not a perfect predictor of autism, but the CSF differences are observable on a standard MRI. “In the future, this sort of CSF imaging could be another tool to help pediatricians detect risks for autism as early as possible,” Shen said. Piven added, “We can’t yet say for certain that improper CSF flow causes autism. But extra-axial CSF is an early marker, a sign that CSF is not filtering and draining as it should. This is important because improper CSF flow may have downstream effects on the developing brain; it could play a role in the emergence of autism symptoms.” The National Institutes of Health, Autism Speaks, and the Simons Foundation funded this research.Other researchers included Sun Hyung Kim, Hongbin Gu, Heather C. Hazlett, Robert W. Emerson, Meghan R. Swanson, and Martin A. Styner at the University of North Carolina; Christine W. Nordahl at UC Davis; Robert C. McKinstry and Kelly N. Botteron at Washington University; Dennis Shaw, Stephen R. Dager, and Annette M. Estes at the University of Washington; Jed T. Elison at the University of Minnesota; Vladimir S. Fonov and Alan C. Evans at McGill University; Guido Gerig at New York University; Sarah Paterson at Temple University; Robert T. Schultz at the University of Pennsylvania; and Lonnie Zwaigenbaum at the University of Alberta.

Newswise — Since the early seventies, scientists have been developing brain-machine interfaces; the main application being the use of neural prosthesis in paralyzed patients or amputees. A prosthetic limb directly controlled by brain activity can partially recover the lost motor function. This is achieved by decoding neuronal activity recorded with electrodes and translating it into robotic movements. Such systems however have limited precision due to the absence of sensory feedback from the artificial limb. Neuroscientists at the University of Geneva (UNIGE), Switzerland, asked whether it was possible to transmit this missing sensation back to the brain by stimulating neural activity in the cortex. They discovered that not only was it possible to create an artificial sensation of neuroprosthetic movements, but that the underlying learning process occurs very rapidly. These findings, published in the scientific journal Neuron, were obtained by resorting to modern imaging and optical stimulation tools, offering an innovative alternative to the classical electrode approach. Motor function is at the heart of all behavior and allows us to interact with the world. Therefore, replacing a lost limb with a robotic prosthesis is the subject of much research, yet successful outcomes are rare. Why is that? Until this moment, brain-machine interfaces are operated by relying largely on visual perception: the robotic arm is controlled by looking at it. The direct flow of information between the brain and the machine remains thus unidirectional. However, movement perception is not only based on vision but mostly on proprioception, the sensation of where the limb is located in space. “We have therefore asked whether it was possible to establish a bidirectional communication in a brain-machine interface: to simultaneously read out neural activity, translate it into prosthetic movement and reinject sensory feedback of this movement back in the brain”, explains Daniel Huber, professor in the Department of Basic Neurosciences of the Faculty of Medicine at UNIGE.Providing artificial sensations of prosthetic movements In contrast to invasive approaches using electrodes, Daniel Huber’s team specializes in optical techniques for imaging and stimulating brain activity. Using a method called two-photon microscopy, they routinely measure the activity of hundreds of neurons with single cell resolution. “We wanted to test whether mice could learn to control a neural prosthesis by relying uniquely on an artificial sensory feedback signal”, explains Mario Prsa, researcher at UNIGE and the first author of the study. “We imaged neural activity in the motor cortex. When the mouse activated a specific neuron, the one chosen for neuroprosthetic control, we simultaneously applied stimulation proportional to this activity to the sensory cortex using blue light”. Indeed, neurons of the sensory cortex were rendered photosensitive to this light, allowing them to be activated by a series of optical flashes and thus integrate the artificial sensory feedback signal. The mouse was rewarded upon every above-threshold activation, and 20 minutes later, once the association learned, the rodent was able to more frequently generate the correct neuronal activity. This means that the artificial sensation was not only perceived, but that it was successfully integrated as a feedback of the prosthetic movement. In this manner, the brain-machine interface functions bidirectionally. The Geneva researchers think that the reason why this fabricated sensation is so rapidly assimilated is because it most likely taps into very basic brain functions. Feeling the position of our limbs occurs automatically, without much thought and probably reflects fundamental neural circuit mechanisms. This type of bidirectional interface might allow in the future more precisely displacing robotic arms, feeling touched objects or perceiving the necessary force to grasp them. At present, the neuroscientists at UNIGE are examining how to produce a more efficient sensory feedback. They are currently capable of doing it for a single movement, but is it also possible to provide multiple feedback channels in parallel? This research sets the groundwork for developing a new generation of more precise, bidirectional neural prostheses. Towards better understanding the neural mechanisms of neuroprosthetic control By resorting to modern imaging tools, hundreds of neurons in the surrounding area could also be observed as the mouse learned the neuroprosthetic task. “We know that millions of neural connections exist. However, we discovered that the animal activated only the one neuron chosen for controlling the prosthetic action, and did not recruit any of the neighbouring neurons”, adds Daniel Huber. “This is a very interesting finding since it reveals that the brain can home in on and specifically control the activity of just one single neuron”. Researchers can potentially exploit this knowledge to not only develop more stable and precise decoding techniques, but also gain a better understanding of most basic neural circuit functions. It remains to be discovered what mechanisms are involved in routing signals to the uniquely activated neuron.

Newswise — Patients treated at mobile health clinics report a high level of engagement in their care and the motivation to pursue healthy behaviors, according to the results of a qualitative study led by Zoe Bouchelle, Harvard Medical School Class of 2017, and communications scholar Heather Carmack of James Madison University. The findings of the analysis suggest mobile clinics are a powerful tool to engage patients in care and to encourage more active participation in their own treatment, the researchers said. The study, which involved in-depth interviews with 25 patients, ages 19 to 72 treated at Family Van mobile clinic, was published online Feb. 14 in Communication Quarterly. Mobile health clinics bring free health care services to underserved communities whose residents may lack the means and transportation to visit a regular clinic or a hospital. “Mobile health clinics are emerging as vital players in the process of rebalancing our health system towards those who have a harder time accessing care,” said study senior author Nancy Oriol, faculty associate dean for community engagement in medical education at HMS. “Such clinics seek to shift the power imbalances and prioritize marginalized voices by listening to patients’ needs and involving them more actively in their own care.” The Family Van provides a range of services, including blood pressure, blood glucose and cholesterol screenings, vision exams, HIV and STI testing, low-cost dental care and counseling, and referrals. It has served more than 100,000 people since its inception 25 years ago. The following dominant themes emerged from participant interviews: • Promoting generosity and inclusion: Participants viewed the Family Van as a vehicle for social justice by helping those in need; providing a safe, welcoming space; and creating a sense of inclusion. Such a view, the researchers point out, underscores the power of mobile health clinics to provide an environment that fosters relationships with patients, which can be difficult to achieve in traditional clinical settings. • Activating an interest in health by sheer presence: Participants reported that the mere presence of the van and the convenience of being able to simply walk in and get tested stimulated their interest in their own health. Patients reported that they were stimulated to seek care due to the fact that services were provided for free, citing co-pays as a major deterrent to seeking care in a standard setting. • Fostering motivation for behavior change: Patients also reported feeling empowered to take an active role in their health as a result of health-related education provided by the mobile clinic staff. In addition to administering tests and screenings, the staff provides recommendations and counseling for long-term care and follow-up. Additionally, many patients reported a desire to encourage family members and friends to be more proactive about their care. Past research has shown that mobile health clinics can help improve blood pressure outcomes among return patients screened, potentially averting dangerous and costly complications. Chronically elevated blood pressure, or hypertension, is a leading cause of stroke, heart disease and kidney damage. More than 2,000 mobile health clinics in the United States provide basic screening and health services, including chronic disease management, prenatal care and pediatric care. There are some 6.5 million visits a year to mobile clinics across the U.S. Researchers estimate that on average, mobile health clinics prevent 600 visits to emergency rooms each year. For more information on the impact of mobile health clinics, visit: http://www.mobilehealthmap.org/impact-report