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Newswise — Bethesda, Md. -- A course at the Uniformed Services University of the Health Sciences (USU) is teaching students global health care delivery in a unique way that’s sure to be a “thriller.” Students in USU’s family nurse practitioner Doctorate of Nursing Practice (DNP) program must take a Population Health course as part of their degree requirements. This online class outlines key principles in responding to and understanding population health – the overall health of a group, be it a group of employees, a community, or entire nation. Students must apply what they learn about theories and models of public health care through debate, small group work, and a series of creative scenarios --including a zombie pandemic. “We use the narrative device of a zombie pandemic in animations and assignment to help engage students in content,” explained Catherine Ling, assistant professor and family nurse practitioner for the DNP and PhD programs, in USU’s Daniel K. Inouye Graduate School of Nursing. The students watch video clips of scenarios, including one of the nation’s “President” delivering a brief “State of the Zombie Pandemic” address. They see the impact that a fictitious zombie virus has made on a population, the fear it’s created – along with “anti-zombie” posters strewn all over cities. These scenarios reinforce teaching materials regarding various tools that shape population health planning and interventions. The zombie coursework keeps the material interesting, Ling said, and the underlying zombie “theme,” throughout each lesson in the module makes it more cohesive. In turn, narrative cohesion makes it easier to remember the material and, therefore, easier to apply should there ever be a real-life population health emergency. As part of a fictitious Department of Defense division, “HHIT,” the students draw on what they’ve learned throughout the course to enact a quarantine, administer widespread vaccines, and obtain international resources, Ling explained. Meanwhile, she added, they must remember to follow actual DoD guidelines, when responding to the “growing zombie pandemic.” The purpose of the course is to provide a working understanding of essential competencies in population health. This skill set is critical in an era of increasing antibiotic resistance, emerging infectious diseases and pandemics like Ebola and Zika. Ling said she’s always looking for ways to keep students engaged by keeping the material relevant and interesting. Adult learning can be enjoyable as well. Those who aren’t into zombies don’t have to watch the videos – they can read the storyline instead. Students have consistently had positive feedback, Ling said, commenting this is “the best online class” they’ve taken. A student in the DNP/FNP who has taken the course, Air Force Capt. Marcie Hart, echoed those sentiments. As a big fan of the TV show “The Walking Dead,” Hart said she was very excited when Dr. Ling mentioned the course would involve a “zombie apocalypse-type scenario.” “The videos are very tastefully done,” Hart said. “The ‘infected’ can be cured later in the scenario, so the characters are not using deadly force, and it is not overtly violent.” Hart added the videos are suspenseful, and exciting. They take somewhat bland, abstract information and make it interesting and concrete. “I thought it was a wonderful, fun twist to this course,” Hart said. While the course is interesting, it also allows the students to use “the other side of their brain,” Ling noted. It gives them a chance to think creatively – and that certainly enhances their problem-solving and critical thinking skills, she said. The online course is also necessary, as a third of the students travel on a temporary duty assignment during the semester. Ling continues focusing on student engagement, looking for ways to make course work interesting and thought provoking. So far, her imaginative efforts have earned her the Teaching with Sakai Innovation Award (TWSIA) for 2015. The award recognizes educators from institutions around the world for their excellence in teaching and learning. # # #   Uniformed Services University of the Health Sciences Military graduate nursing students use zombies to learn how to work through a public health crisis in the Daniel K. Inouye Graduate School of Nursing Population Health course at the Uniformed Services University of the Health Sciences in Bethesda, Md.
Newswise — The Food and Drug Administration has approved the first focused ultrasound device to treat essential tremor, the most common movement disorder, in patients who do not respond to medication. The scalpel-free approach has been pioneered by Jeff Elias, MD, at theUniversity of Virginia School of Medicine, who led an international clinical trial that demonstrated the safety and effectiveness of the device. “This is a monumental day for people with essential tremor,” Elias said. “All patients want more options that are less invasive when they are faced with a surgical procedure. Also, this decision represents a great advance for focused ultrasound technology, which is now capable and available to treat disorders of the brain. Soon we are likely to see this incredible technology applied to other conditions and diseases of the brain.” How Focused Ultrasound WorksThe technology focuses sound waves inside the brain to create heat, much like a magnifying glass focuses light. That heat can then be used to carefully interrupt circuits of the brain that are responsible for the tremor. With magnetic resonance imaging, Elias can monitor the location and intensity of the procedure in real-time – an important safety feature when making a precise lesion deep inside the brain. He can actually watch as the tremor reduces. Elias oversaw an international clinical trial of the device tested in 76 patients with severe tremor who had not responded to medication. Fifty-six participants in the double-blind study received the procedure, while 20 others were in a control group that received a sham procedure. The results were dramatic: Overall, those treated saw their tremor reduced by half after three months and by 40 percent after a year. That’s comparable to the results of deep-brain stimulation, an invasive surgery that involves placing electrodes inside the brain. Unlike with deep-brain stimulation, patients who receive the focused-ultrasound procedure are treated without incisions or the implantation of neurostimulator devices. The most common side effects of the procedures were sensory changes like numbness or tingling as well as balance disturbance that tended to be transient. Nineteen of the 20 patients who received the sham procedure during the trial went on to receive the focused-ultrasound procedure. Now Available for PatientsThe FDA approval of the ExAblate focused ultrasound device, manufactured by InSightec Inc., means UVA can make the procedure available to eligible patients. It is important to note, however, that insurance plans will not yet cover the procedure. The cost at UVA has not yet been determined. People interested in the procedure can learn more at: uvahealth.com/focusedultrasound The procedure cannot be used in patients who cannot undergo magnetic-resonance imaging, including those with implanted metallic devices such as a pacemaker. It is also not available for pregnant women, people with heart conditions or very high blood pressure, patients with kidney disease or clotting disorders, patients on blood thinners, patients with a history of strokes or brain tumors and people with substance abuse issues. There are other exclusions as well. Doctors at UVA will evaluate potential patients to determine their eligibility and then recommend the best course of treatment. Groundbreaking ResearchUVA is a world-leader in focused ultrasound research. Elias and other scientists are testing the capability of focused ultrasound to treat Parkinson’s disease, epilepsy, brain tumors, and benign breast tumors. The research has been supported by the Focused Ultrasound Foundation and the BIRD (U.S.-Israel Binational Industry Research and Development) Foundation. “This milestone was accomplished as the result of the leadership of Dr. Elias in a collaborative effort between academic institutions, industry and philanthropic organizations,” said Neal F. Kassell, MD, chairman of the Focused Ultrasound Foundation.
Newswise —  Available research suggests that noninvasive stimulation of a specific brain area can reduce food cravings—particularly for high-calorie, "appetitive" foods, according to a review in the Psychosomatic Medicine: Journal of Biobehavioral Medicine, the official journal of theAmerican Psychosomatic Society. The journal is published by Wolters Kluwer. However, there's not yet consistent evidence to show that brain stimulation can reduce actual food consumption, according to the research review by Peter A. Hall, PhD, of University of Waterloo, Ont., Canada, and colleagues. Brain Stimulation May Curb Your Cravings—Especially for CarbsThe researchers analyzed previous studies evaluating the effects of noninvasive brain stimulation on food cravings and food consumption. Stimulation studies have targeted a brain area called the dorsolateral prefrontal cortex (DLPFC), which appears to play a role in the "conscious regulation of food craving and consumption of calorie-dense foods." The review identified eleven studies evaluating the effects of DLPFC stimulation on food cravings and/or consumption. The studies included human volunteers in laboratory settings—most often women who reported "strong and frequent" cravings for high-calorie snack foods. All studies used an appropriate sham (inactive) stimulation procedure. Of eight studies providing data on food cravings, all but one showed a significant effect of brain stimulation. Meta-analysis of pooled data from these studies suggested a "moderate-sized effect" of DLPFC stimulation on food cravings—roughly half a point on a four-point self-rated scale. Just one of the two types of stimulation studied had a significant effect on food cravings—a technique called repetitive transcranial magnetic stimulation (rTMS). The other technique evaluated, transcranial direct current stimulation, did not significantly affect cravings. In contrast, the results of nine studies providing data on actual food consumption were inconsistent. The pooled data analysis suggested no significant effect of brain stimulation. Another two studies evaluated the effects of treatment using repeated sessions of DLPFC stimulation. One study found a significant reduction in total food intake after daily stimulation, while the other did not. However, there was some evidence that stimulation specifically reduced consumption of carbohydrates—for example, cookies, cakes, and soda. That's important, because calorie-dense snack foods are often implicated in the development of obesity. One reason it's so difficult to lose weight by dieting is that the person has to overcome the "natural preferences" for these types of appetitive foods. It's not entirely clear how DLPFC works to reduce food cravings, but evidence suggests possible effects on the "reward center" of the brain and/or enhanced cognitive control over cravings. The available data support the conclusion that DLPFC stimulation reduces food cravings, Dr. Hall and coauthors believe. "These effects seem to be strongest for rTMS neuromodulation methods and are moderate in magnitude," they write. While so far there's "no reliable effect" of brain stimulation in reducing overall food consumption, studies do suggest a possible effect on intake of carbohydrates. Dr. Hall and colleagues make suggestions for future research, clarifying the potential benefits of repeated sessions of rTMS and focusing on actual food consumption—especially calorie-dense snack foods. Click here to read "Effects of Noninvasive Brain Stimulation on Food Cravings and Consumption: A Meta-Analytic Review." Article: "Effects of Noninvasive Brain Stimulation on Food Cravings and Consumption: A Meta-Analytic Review." (doi; 10.1097/PSY.0000000000000368) ###
Newswise — CHICAGO – It’s just a matter of time before many different foods have “intelligent packaging,” a term used to describe package features that communicate information such as shelf life, freshness and quality, according to a presentation at a July 18 symposium at IFT16: Where Science Feeds Innovation, hosted by the Institute of Food Technologists (IFT). “We need consumer-friendly sensors for products that say, “Hey, this food is fresh and safe to eat, or it isn’t,” says Claire Sand, an adjunct professor of packaging at Michigan State University and owner of Packaging Technology & Research. “We’re very close to being able to do for a multitude of foods.” Intelligent packaging is already used on some medicines and food products, but it will become more widespread in the next few years due to the interest in reducing food waste, she says. Time-temperature indicators have been around for a while and are widely used, especially on seafood packages to ensure the products are safe, she says. They take into account time and temperature which are tied to deterioration. For instance, fish or chicken left out on the counter will spoil faster than if it’s kept in the refrigerator or freezer, she says. New degradation sensors work even better than time-temperature indicators because they actually measure products’ decay, Sand says. These sensors can be integrated into the packaging to detect spoilage and help reduce food waste. For instance, an entire package film may change color when certain chemical reactions, such as food decay, occur, Sand says. Degradation sensors or time temperature indicators may also be small tags that change color when the product is no longer edible. In some cases, the bar codes fade so the food can’t be purchased, she says. About 30% of food in the United States is wasted between production and consumption, Sand says. “Giving consumers clear direction on what food is still good and what food is past its shelf life will reduce food waste, which is a huge problem in the United States and other countries.” As the price of food increases, consumers increasingly need a way to assess the quality of the food they buy, she says.
Newswise —  Programs to reduce the high risk of HIV infection among transgender people are urgently needed—but efforts are hindered by a lack of accurate information on HIV prevalence, HIV incidence, and specific risk factors facing this key population. A special supplement to JAIDS: Journal of Acquired Immune Deficiency Syndromes presents essential information to meet the challenges of HIV prevention in the transgender population. The journal is published by Wolters Kluwer. "The 'Transgender supplement' has been developed to fill critical gaps in information on the state of the HIV epidemic among transgender individuals, to discuss opportunities for culturally-tailored prevention interventions, and to inform the way forward in responding to the unique public health challenge in this often marginalized and underserved population," according to Guest Editors Kenneth Mayer of Fenway Health, Boston; Beatriz Grinsztejn of Fundação Oswaldo Cruz, Rio de Janeiro; and Wafaa M. El-Sadr of Columbia University, New York. The full contents of the special issue are freely available on the JAIDS website: www.jaids.com. Experts Seek to Build Evidence for Effective HIV Prevention in Transgender PeopleAlthough transgender individuals account for less than one percent of the population, they have a "distinctively increased" burden of HIV disease. Recent estimates suggest that the worldwide prevalence of HIV among transgender women is 19 percent—with odds HIV close to 50 times higher than in non-transgender adults of reproductive age. Historically, HIV researchers and public health officials have grouped transgender women in the category of "men who have sex with men" (MSM). But that overlooks the multi-level factors—sexual behaviors, social networks, and discrimination, among others—that may contribute to HIV risk in transgender women. Even less is known about HIV risk and risk factors among transgender men. Knowledge gaps exist in other areas as well, including the effectiveness of pre-exposure prophylaxis (PrEP) using antiretroviral drugs to decrease HIV transmission. Social stigma and the threat of violence may prevent transgender people from accessing available testing, prevention, and treatment services. "Developing effective programs to reduce HIV in transgender individuals will require an in-depth understanding of the epidemiology of behaviors and risks with specific types of partners in the diverse cultures where transgender people live," according to Dr. Mayer and colleagues. Building on a recent workshop sponsored by the HIV Prevention Trials Network (HPTN), the eight papers in the special issue frame the important issues in developing a more holistic approach to the engagement of HIV prevention interventions for transgender individuals. Topics include: • A comprehensive analysis of data on the epidemiology of HIV in transgender people.• Potential for interactions between antiretroviral drugs and hormone therapy used by some transgender individuals—a key factor in evaluating the use of PrEP.• Initial data and research priorities on PrEP in transgender women.• A "holistic framework" for understanding the health needs of transgender people.• Behavioral approaches to improving HIV protection for transgender women. Other papers address critical research considerations: developing effective and sensitive strategies for engaging transgender people in HIV clinical trials, statistical issues in studying this and other small population groups at high risk of HIV, and ethical considerations for research with transgender individuals. The supplement will be highlighted at this year's 21st International AIDS Conference, to be held in Durban, South Africa, July 18 to 22. "This special issue is a ground-breaking synthesis of the state-of-the-art and an insightful roadmap to meet the urgent challenge of addressing an underserved 'key population' at the heart of the WHO 90-90-90 campaign for HIV in transgender populations," comments Dr. William A. Blattner, Co-Editor of JAIDS. Click here to read "Transgender People and HIV Prevention: What We Know and What We Need to Know, a Call to Action." Article "Transgender People and HIV Prevention: What We Know and What We Need to Know, a Call to Action." (doi; 10.1097/QAI.0000000000001086) ###
Newswise — La Jolla, Calif., — Scientists at the Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified over 100 new genetic regions that affect the immune response to cancer. The findings, published in Cancer Immunology Research, could inform the development of future immunotherapies—treatments that enhance the immune system’s ability to kill tumors. “By analyzing a large public genomic database, we found 122 potential immune response drivers—genetic regions in which mutations correlate with the presence or absence of immune cells infiltrating the tumors,” said lead author Eduard Porta-Pardo, Ph.D., a postdoctoral fellow at SBP. “While several of these correspond to proteins with known roles in immune response, many others offer new directions for cancer immunology research, which could point to new targets for immunotherapy.” Immunotherapy has been heralded as a turning point in cancer because it can treat even advanced cases that have spread to other organs. Several drugs in this class are now widely used and often lead to remarkable success, eradicating or dramatically shrinking tumors and preventing recurrence. Most current immunotherapies rely on a similar strategy—releasing the brakes on the immune system. These treatments are powerful if the tumor is recognized by the immune system as a threat and allows immune cell infiltration, but some cancers remain undercover or block immune cell entry into the tumor in as yet unknown ways. “To develop immunotherapies that are relevant to a wide range of cancers, we need to know a lot more about how the immune system interacts with tumors,” said Adam Godzik, Ph.D., professor and director of the Bioinformatics and Structural Biology Program and senior author of the study. “Our study provides many new leads for this endeavor.” “We are exploring cancer mutations at fine resolution by accounting for the fact that mutations can affect the encoded protein in different ways depending on where the resulting change is located,” commented Porta-Pardo. “Our algorithm, domainXplorer, identifies correlations between a phenotype, in this case the amount of immune cells in the tumor, and mutations in individual protein domains—parts of a protein with distinct functions. “This work emphasizes the value of open data,” Godzik added. “Because we could access genomic data from over 5,000 tumor samples from The Cancer Genome Atlas (TCGA), we could jump straight to analysis without having to set up a big collaborative network to gather and sequence so many samples.” “Our plan for the next phase of this research is to use this algorithm to search for genetic regions correlating with the levels of specific immune cell types within the tumor, which will reveal further details of cancer immunology.” This research was supported in part by a National Cancer Institute center grant (P30 CA030199). # # # #
Newswise — NEW YORK, NY, — A toxic Alzheimer’s protein can spread through the brain—jumping from one neuron to another—via the extracellular space that surrounds the brain’s neurons, suggests new research from Columbia University Medical Center. The study has been published online in Nature Neuroscience. The spread of the protein, called tau, may explain why only one area of the brain is affected in the early stages of Alzheimer’s but multiple areas are affected in later stages of the disease. “By learning how tau spreads, we may be able to stop it from jumping from neuron to neuron,” said Karen Duff, PhD, professor in the department of pathology and cell biology (in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain) and professor of psychiatry (at New York State Psychiatric Institute.) “This would prevent the disease from spreading to other regions of the brain, which is associated with more severe dementia.” The idea the Alzheimer’s can spread through the brain first gained support a few years ago when Duff and other Columbia researchers discovered that tau spread from neuron to neuron through the brains of mice. In the new study, lead scientist Jessica Wu, PhD, a former post-doctoral researcher at the Taub Institute who is currently at Massachusetts Institute of Technology, discovered how tau travels by tracking the movement of tau from one neuron to another. Tau, she found, can be released by neurons into extracellular space, where it can be picked up by other neurons. Because tau can travel long distances within the neuron before its release, it can seed other regions of the brain. “This finding has important clinical implications,” explained Dr. Duff. “When tau is released into the extracellular space, it would be much easer to target the protein with therapeutic agents, such as antibodies, than if it had remained in the neuron.” A second interesting feature of the study is the observation that the spread of tau accelerates when the neurons are more active. Two team members, Abid Hussaini, PhD, and Gustavo Rodriguez, PhD, showed that stimulating the activity of neurons accelerated the spread of tau through the brain of mice and led to more neurodegeneration. Although more work is needed to examine whether those findings are relevant for people, “they suggest that clinical trials testing treatments that increase brain activity, such as deep brain stimulation, should be monitored carefully in people with neurodegenerative diseases,” said Dr. Duff. The study is titled, “Neuronal activity enhances tau propagation and tau pathology in vivo.” Authors included Jessica W. Wu, S. Abid Hussaini, Isle Bastille, Gustavo A. Rodriguez, Kelly Rilett, Hongjun Fu, Rick A. C. M. Boonen, Mathieu Hreman, Eden Nahmani, Sheina Emrani, Y Helen Figueroa, Catherine L. Clelland, and Karen E. Duff (Taub Institute, Columbia University Medical Center, New York, NY), Ana Mrejeru (Department of Neurology, Columbia University Medical Center, New York, NY), David W. Sanders and Marc I. Diamond (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX), Casey Cook (Department of Neuroscience, Mayo Clinic, Jacksonville, FL), and Selina Wray (Institute of Neurology, University College, London, UK). This work was supported by a BrightFocus Foundation fellowship, NIH/NINDS grants NS081555 and NS074874, Cure Alzheimer's Fund, the Parkinson's Disease Foundation, NIH/NIA grants AG050425 and AA19801, and the NIHR Queen Square Dementia Biomedical Research Unit. The authors declare no competing financial interests. -####-
Newswise — A study led by Washington University School of Medicine in St. Louis, in collaboration with Brigham and Women’s Hospital in Boston, has identified a genetic error that weakens the aorta, placing patients with this and similar errors at high risk of aortic aneurysms and ruptures. The findings will help diagnose, monitor and treat patients with aortic disease not caused by well-known conditions, such as Marfan syndrome and other genetic mutations known to disrupt connective tissues. The study appears July 18 in the Proceedings of the National Academy of Sciences. Working with the Brigham Genomic Medicine Program, the researchers identified the mutation in a family with a history of aortic disease but no known genetic reason for the condition. The error is in a gene called lysyl oxidase (LOX), which Washington University researchers have shown is responsible for connecting networks of tissue fibers that make up blood vessels. The aorta is the body’s largest artery that carries blood from the heart to the rest of the body. A lifetime of smoking and poor cardiovascular health can lead to aortic aneurysms in older adults. But bulging and tearing of the aorta in a young person is most often due to an inherited condition. A number of genetic mutations, including those that cause Marfan syndrome and Loeys-Dietz syndrome, are known to interfere with the integrity of connective tissues. Such weakening puts patients at high risk of death from a ruptured aorta. Standard genetic tests often pinpoint the reason for inherited aortic disease, but such tests can’t explain all cases. “When a patient comes to the clinic with an enlarged aorta, clinicians can evaluate a standard list of genes to look for a cause of the condition,” said senior author Nathan O. Stitziel, MD, PhD, a Washington University cardiologist and assistant professor of medicine. “Lysyl oxidase should now be added to the standard test panel. This type of information can provide clarity for families with histories of unexplained aortic aneurysms.” The findings also may allow affected individuals to be identified early, before the aorta begins to enlarge, so that doctors can help these patients take steps to lower pressure on the aorta, and decide when surgery may be required to prevent a sudden rupture. To confirm that this mutation was the cause of the weakened aorta rather than an association, Stitziel and his colleagues recreated the genetic mistake in mice using the gene editing technology CRISPR. Washington University’s Robert P. Mecham, PhD, the Alumni Endowed Professor of Cell Biology and Physiology, and graduate student Vivian Lee showed that mice with two copies of the mutated gene died of aortic rupture at birth. Mice with only one copy — like members of the family the researchers identified with the mutation — had disrupted collagen and elastin fibers in the aorta. “The layers and fibers of the aorta are almost like the belts inside a tire,” Stitziel said. “You have to have the right structure to maintain the strength and integrity of the artery. Lysyl oxidase crosslinks the fibers together. When there is less lysyl oxidase than there should be, the proper structure is disrupted. And when lysyl oxidase is absent altogether, the mice don’t survive after birth.” Stitziel added that the mouse model of the condition will enable the researchers to test new potential therapies for this type of aortic disease. In particular, the investigators pointed out that lysyl oxidase is known to perform its job of crosslinking fibers better when bound to copper, raising the possibility that such patients may benefit from therapies involving dietary copper. “When we found this causal gene and were able to reveal it to the family, it was an emotional moment,” said Natasha Frank, MD, a clinical geneticist who treated several members of the family at Brigham and Women’s Hospital. “Using genetic sequencing, we were able to answer the kind of question that hasn’t been possible to address before and potentially change the lives of family members who can now be tested for mutations in this gene.” ### This work was supported, in part, by the Hope Center Transgenic Vectors Core and Mouse Genetics Core at the Washington University School of Medicine; the National Heart Lung and Blood Institute of the National Institutes of Health (NIH), grant numbers R01HL105314, R01HL53325, K08HL114642, R01HL131961, T32EB18266-1, and T32HL07873; the Child Health Research Center at Washington University School of Medicine, grant number K12-HD076224; The Foundation for Barnes-Jewish Hospital; the Center for Integrated Approaches to Undiagnosed Diseases, grant numbers U01 HG007690-01 NIH/NHGRI; and a Brigham Research Institute (BRI) Director’s Transformative Award. Lee V, Halabi CM, Hoffman EP, Carmichael N, Leshchiner I, Lian C, Bierhals A, Vuzman D, Brigham Genomic Medicine Program, Mecham R, Frank NY, Stitziel N. Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans. Proceedings of the National Academy of Sciences. July 18, 2016. Washington University School of Medicine‘s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.
Newswise — DETROIT – Noa Ofen, Ph.D., a Wayne State University researcher in lifespan cognitive neuroscience, received a five-year, $1.9 million grant from the National Institute of Mental Health of the National Institutes of Health to study the development of memory networks in children. Researchers will investigate brain activity predictive of memory formation in children who undergo surgery as part of clinical management of medically uncontrolled epilepsy. “Little is known about how memory systems develop in the human brain,” Ofen said. “In this project, we will use a combination of unique neuroimaging methodologies that allow us to add new insights about the neural basis of memory development. We also hope this project will be a first step toward clinical applications that can ultimately improve the quality of life of children with focal epilepsy.” Commonly used noninvasive neuroimaging methods — such as functional MRI (fMRI) or EEG — cannot simultaneously measure the spatial and temporal dimensions of the neural correlates of memory at high resolution. In this project, the researchers will use intracranial EEG recordings — also referred to as electrocorticography (ECoG) — from electrodes implanted directly on the surface of the brain of pediatric patients undergoing pre-surgical brain mapping as part of clinical management of epilepsy. ECoG provides excellent spatial and temporal resolution, making it a powerful tool for examining the neural basis of human memory. The researchers will capture the temporal dynamics of information flow in the brain that are predictive of whether studied information or experiences will be remembered. Ofen will use ECoG to map memory networks in patients and collect additional fMRI data from a subset of these patients and a large sample of matched healthy children to determine age differences in activation and patterns of functional connectivity between key regions in the memory network. “Our overarching goal is to identify the spatial and temporal dynamics of memory networks in the developing human brain,” Ofen said. She also hopes to lay the foundation to extend mapping of the brain’s “eloquent tissue” in children to include pre-surgical brain mapping of memory networks to reduce the post-surgery memory decline that can occur after surgical removal of the seizure focus. This memory decline is directly linked to health-related decreased quality of life in later years. Ofen is jointly appointed to Wayne State’s Department of Psychology in the College of Liberal Arts and Sciences and the Institute of Gerontology’s Lifespan Cognitive Neuroscience Program that — together with research laboratories at the Merrill Palmer Skillman Institute for Child & Family Development — apply a cognitive neuroscience approach to study developmental effects from pre-birth to old age. The project is in collaboration with Wayne State University School of Medicine faculty member Eishi Asano, M.D., a member of the Epilepsy Surgery Program at Children’s Hospital of Michigan; Vaibhav Diwadkar, Ph.D.; Robert Rothermel, Ph.D.; and Harry Chugani, M.D. (now at Nemours/Alfred I. duPont Hospital for Children in Delaware). Robert Knight, M.D., of the University of California, Berkeley, is also an integral member of this project.
Newswise — Bacteria are rapidly developing resistance mechanisms to combat even the most effective antibiotics. Each year in the United States over 23,000 people die as a result of bacterial infections that have no treatment options, according to the Centers for Disease Control. Infections with antibiotic-resistance bacteria are extremely difficult to treat, requiring costly or toxic medications that do not always work. Scientists are constantly working to understand the mechanisms bacteria use to outsmart antibiotics and develop resistance. These mechanisms include metallo-β-lactamases (MBLs), enzymes produced by bacteria that can bind to and inactivate antibiotics. Enzymes like MBLs are one way bacteria are defying all available tools and becoming antibiotic resistant. A team of researchers at Case Western Reserve University (CWRU), Massachusetts Institute of Technology, and Universidad Nacional de Rosario and the National Research Council (CONICET) from Argentina have identified a bacterial mechanism that stabilizes certain MBLs in cell membranes and enables their spread into the environment. This mechanism clarifies one way certain bacteria are outsmarting the immune system and becoming extremely antibiotic-resistant. The work was led in part by Robert Bonomo, MD, professor of medicine, pharmacology, molecular biology, and microbiology at Case Western Reserve University School of Medicine and chief of medical service at the Louis Stokes Cleveland Veterans Affairs Medical Center. “One of the most serious problems facing medicine today is the emergence of multi-drug resistant bacteria,” according to Bonomo. “MBLs are the most concerning as they make bacteria resistant to the ‘last resort’ antibiotics, carbapenems.” Carbapenems are used to combat infections for which there are no other antibiotic options. Clinically relevant MBLs are found between layers of bacterial cell membranes. In contrast to other types of carbapenemases, MBL enzymes rely on zinc ions to properly function. The immune system produces proteins that hide zinc ions and starve bacteria of zinc in an effort to combat infection. The researchers discovered that most MBLs produced by bacteria during zinc-limited conditions are unstable and are rapidly degraded by the bacteria. One recently identified form of MBL, called New Delhi metallo-β-lactamase (NDM-1) can retain its function even without zinc. Bonomo and colleagues showed that NDM-1 resists destruction triggered by low zinc by anchoring itself in bacterial membranes. A fatty tail at one end of the NDM-1 protein sticks into the outer membrane of potentially harmful bacteria such as Escherichia coli and Pseudomonas aeruginosa. This tail has a protective effect and is thought to help NDM-1 avoid destructive enzymes between bacterial membranes. Similar mechanisms have been observed in other bacterial species, but have not previously been linked to an evolutionary advantage to escape the action of antibiotics. The research team also observed that bacteria with NDM-1 in their membranes are also able to shed “outer-membrane vesicles” containing the enzyme. These membrane-bound sacs bud off from bacteria. As the vesicles disperse into the bacterial microenvironment, NDM-1 enzymes in them can protect neighboring bacteria that might be otherwise susceptible to antibiotics. Outer-membrane vesicles may also be a vehicle by which the NDM-1 gene and enzyme can spread between bacteria. Bacteria producing NDM-1 are highly antibiotic resistant and represent a major public health concern as they cause infections for which there is no cure. The gene encoding NDM-1 is quickly spreading across bacterial species and has been found in water samples from India, Bangladesh, and China in a region encompassing almost 40% of the world population.According to Alejandro Vila, PhD, director of the Instituto de Biología Molecular y Celular at Universidad Nacional de Rosario and co-senior author on the published research, “this dissemination has been favored by membrane anchoring of the protein. This finding reveals a potential Achilles’ heel; interfering with membrane anchoring could thwart the worldwide dissemination of superbugs.” Together, the studies by Bonomo, Vila, and colleagues provide clarity on the bacterial mechanism behind one of the most prevalent bacterial carbapenemase identified to date, NDM-1. Understanding the mechanism “allows us to begin considering novel agents that can target this process,” according to. Bonomo. New potential targets for antibacterial drug development could include the lipid tail of NDM-1 or outer membrane vesicles. The research findings first appeared online in the May 2016 edition of Nature Chemical Biology. The research was supported by National Institutes of Health research grants R01AI072219, R01AI063517 and R01AI100560, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, the VISN 10 Geriatric Research, Education and Clinical Care Center (VISN 10) of the Department of Veterans Affairs, the Kinship Foundation (Searle Scholars Program), the Argentinian ANCPCyT and CONICET, and MIT Department of Chemistry.