Joshua C. Gross, M.D., a first-year resident in training with the UofL Department of Ophthalmology and Visual Sciences, will present his research at the annual meeting of the Association of University Professors of Ophthalmology (AUPO) on Jan. 26 in Austin, Tex. At the RPB/AUPO Resident and Fellow Research Forum. Gross has conducted research into the association between blood flow in the retina and the progression of open-angle glaucoma and diabetes mellitus.

Working with colleagues at Indiana University School of Medicine and in Italy, Gross found that patients who had reduced retinal blood flow and optic nerve damage consistent with glaucoma who also had diabetes experienced faster visual deterioration than patients with similar characteristics but who did not have diabetes.

Open-angle glaucoma, the most common form of glaucoma, accounts for at least 90 percent of all glaucoma cases, affecting about 3 million Americans. It is caused by the slow clogging of the drainage canals, resulting in increased eye pressure. 

January 25, 2018

In a study of patients with head and neck cancer, even mild depressive symptoms were associated with poorer overall survival. Published early online today in CANCER, a peer-reviewed journal of the American Cancer Society, the findings indicate that patients should be screened and treated for depressive symptoms at the time of diagnosis. In addition, studies should examine parallel biological pathways linking depression to cancer survival.

Many patients diagnosed with head and neck cancer experience symptoms of depression, which can make it difficult for them to manage treatment side effects, quit smoking, or maintain adequate nutrition or sleep habits. A team led by Elizabeth Cash, Ph.D., of the University of Louisville School of Medicine, was interested to see if depressive symptoms might also affect patients’ health outcomes.

The researchers studied 134 patients with head and neck cancers being treated at the UofL James Graham Brown Cancer Center multidisciplinary head and neck clinic from October 2012 to October 2013 who reported depressive symptoms during the planning of their treatment. In this group, 67.2 percent expressed measureable depressive symptoms. When the investigators examined the patients’ clinical data over the following two years, they found that patients with greater depressive symptoms had shorter survival, higher rates of chemo-radiation interruption, and poorer treatment response.

“We observed that head and neck cancer patients who reported more depressive symptoms at their initial appointment were more likely to miss scheduled treatment appointments and were more likely to have tumors that persisted after medical treatment,” said Cash, who serves as the director of research for the Department of Otolaryngology-Head and Neck Surgery and Communicative Disorders at UofL. “We also observed that patients with depressive symptoms suffered greater two-year overall mortality rates, and this was especially true for those who did not achieve optimal response to medical treatment.”

Poorer treatment response partially explained the depression-survival relationship; however, there were no significant effects from factors commonly used to determine cancer prognosis—such as the patient’s age, the stage of tumor advancement or extent of smoking history.

“This suggests that depressive symptoms may be as powerful as the clinical features that physicians typically use to determine the prognosis of patients with head and neck cancer,” Cash said.

She also noted that most patients in the study did not meet criteria for diagnosis of major depressive disorder, suggesting that even mild symptoms of depression may interfere with head and neck cancer treatment outcomes. She said that while the findings need to be replicated in a larger study, they do suggest that depressive symptoms may affect head and neck cancer patients’ survival through mechanisms that potentially coincide with the activities of their tumor.

“We want patients to know that it is normal to get depressed when they are diagnosed, but it is important to seek help for any depression symptoms because (not doing so) may lead to poorer outcomes related to their cancer treatment,” Cash said.

She and her colleagues are hopeful that this information can facilitate discussions between patients and psycho-oncologists or behavioral oncology specialists to expedite the development of targeted behavioral interventions, which may have high potential to complement medical treatment efficacy.

Eating disorders affect about 8 million people in the United States at any one time. Although a large majority is young women, anorexia nervosa, bulimia nervosa and other types of eating disorders can affect men and people of any age. Cheri Levinson, Ph.D., assistant professor in the Department of Psychological and Brain Sciences and director of the Eating Anxiety Treatment Laboratory at the University of Louisville, will share some of her research in the treatment of eating disorders at the next Beer with a Scientist event, Wednesday, Jan. 17.

Levinson will discuss the lab’s research on the association between eating disorders and anxiety. In addition, she will describe therapies that incorporate technological innovations.

“The most common treatments for eating disorders only work for about 50 percent of individuals,” Levinson said. “In the Eating Anxiety Treatment Lab, we are working on developing novel treatments personalized to the individual,” Levinson said. “Many of our treatments use technology to help improve treatment and reach more people.”

Levinson’s talk begins at 8 p.m. onWednesday, Jan. 17, at Against the Grain Brewery, 401 E. Main St. in Louisville. A 30-minute presentation will be followed by an informal Q&A session.

Admission is free. Purchase of beer, other beverages or menu items is not required but is encouraged.

Organizers add that they also encourage Beer with a Scientist patrons to drink responsibly.

UofL cancer researcher Levi Beverly, Ph.D., created the Beer with a Scientist program in 2014 as a way to bring science to the public in an informal setting. Once a month, the public is invited to enjoy exactly what the title promises:  beer and science. For more information and to suggest future Beer with a Scientist topics, follow Louisville Underground Science on Facebook.

Upcoming Beer with a Scientist dates:  Mar. 14, Apr. 18.

January 9, 2018

Research in the past two decades has revealed that microbial organisms in the gut influence health and disease in many ways, particularly related to immune function, metabolism and resistance to infection. Recent studies have shown that gut microbes also may cause or worsen Parkinson’s disease, Alzheimer’s disease and other neurodegenerative conditions.

University of Louisville neurology professor Robert P. Friedland, M.D., and Matthew R. Chapman, Ph.D., professor at the University of Michigan, have proposed a new term to describe an interaction between gut microbiota and the brain in an article released today in PLOS Pathogens.

Friedland and Chapman propose the term “mapranosis” for the process by which amyloid proteins produced by microbes (bacteria, fungi and others) alter the structure of proteins (proteopathy) and enhance inflammation in the nervous system, thereby initiating or augmenting brain disease. The term is derived from Microbiota Associated Protepathy And Neuroinflammation + osis (a process).

Friedland hopes that giving the process a name will facilitate awareness of the process, as well as research leading to therapeutic opportunities.

“It is critical to define the ways in which gut bacteria and other organisms interact with the host to create disease, as there are many ways in which the microbiota may be altered to influence health,” Friedland said.

Research into the multitude of microbes that inhabit the human body has expanded considerably in recent years. Genomic analysis has begun to reveal the full diversity of bacteria, viruses, fungi, archaea and parasites living in and on the body, the majority of them in the gut. Even more recently, researchers have begun to explore how the proteins and other metabolites produced by microbes inhabiting the gut influence functions in other parts of the body, including the brain. However, we do not yet have a full understanding of how these systems work. The relationship between the microbiota and the brain has been called the “gut-brain axis.”

It is understood that the clumping of misfolded amyloid proteins, structures produced by neurons in the brain, are associated with neurodegeneration and conditions such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS).

“It is well known that patterns of amyloid misfolding of neuronal proteins are involved in age-related brain diseases. Recent studies suggest that similar protein structures produced by gut bacteria, referred to as bacterial amyloid, may be involved in the initiation of neurodegenerative processes in the brain,” Friedland said. “Bacterial amyloids are produced by a wide range of microbes that inhabit the GI tract, including the mouth.”

In research published in 2016 in Scientific Reports, Friedland and colleagues showed that when E. coli microbes in the gut of rats and worms (nematodes) produced misfolded amyloids, the amyloids produced in the animals’ brains and intestines also misfolded, a process called cross-seeding.

“Our work suggests that our commensal microbial partners make functional extracellular amyloid proteins, which interact with host proteins through cross-seeding of amyloid misfolding and trigger neuroinflammation in the brain,” Friedland said.

In today’s article, Friedland and Chapman also address other factors related to the microbiota and its products and how they influence neurodegenerative disorders.

1. The microbiota modulates (enhances) immune processes throughout the body, including the central nervous system.
2. The microbiota may induce oxidative toxicity (free radicals) and related inflammation that contributes to neurodegeneration.
3. Metabolites produced by the microbiota may be either beneficial (health sustaining) or damaging (pathogenic).
4. Host genetics influence microbiota populations, illustrating that the gut-brain axis is bidirectional.

Friedland believes further research in this area may lead to therapies for these neurodegenerative diseases, which are increasing in frequency and for which there are few effective treatments.

Chapman’s research is supported by the National Institutes of Health. Friedland’s work has been supported by The Michael J. Fox Foundation.

December 21, 2017

Nearly 900 toys swamped a Christmas tree in the University of Louisville Health Sciences Center administration building, ready to be delivered to local children who would otherwise go without presents this year.

For the third year, the UofL School of Medicine House Staff Council, the representative body for resident and fellow physicians, led a weeklong collection for Toys for Tots. Donations were received from individual residents and fellows as well as School of Medicine faculty, staff and students.

“Unfortunately, there are so many families in Louisville who cannot afford toys for their children,” said Svetlana Famina, M.D., a third-year psychiatry resident. “We work with these families a lot on a daily basis, so we know how much things like this are appreciated by children and their parents.”

Stock Yards Bank & Trust will provide a luncheon and plaque to the three residency programs that donated the most toys.

The winning program for the third straight year, the Department of Psychiatry and Behavioral Sciences, collected about 430 toys. Aside from gathering donated toys, psychiatry residents raised about $1,000 to buy additional gifts, Famina said.

The Department of Obstetrics, Gynecology and Women’s Health donated the second-most number of toys and the Department of Radiology finished third.

Jamie Morris, M.D., a radiology resident, said the annual toy drive has become an important way for UofL medical residents to give back to the community, especially children.

“It’s important to share what we have,” Morris said. “The residency program is a strong coalition and we have a lot to give the Louisville community.”

Staff members of the Office of Graduate Medical Education sorted and packed the toys in donation boxes, which were picked up by a Toys for Tots volunteer on Dec. 11.

The U.S. Marine Corps Reserve Toys for Tots Program collects new, unwrapped toys during October, November and December each year, and distributes those toys as Christmas gifts to underprivileged children in the community in which a campaign is conducted.

Senior citizens who live in Jefferson and surrounding Kentucky counties are encouraged to take a brief survey online or over the phone to help analyze social service needs for older adults and individuals with disabilities.

For the second year, the University of Louisville Institute for Sustainable Health and Optimal Aging will conduct a community needs assessment on behalf of the Kentuckiana Regional Planning & Development Agency (KIPDA).

Led by the institute’s Executive Director, Anna Faul, Ph.D., and Director of Health Innovation and Sustainability, Joe D’Ambrosio, Ph.D., the 2018 KIPDA needs assessment surveys people across the seven KIPDA counties – Bullitt, Henry, Oldham, Shelby, Spencer, Trimble and Jefferson. It looks at each county in regards to housing, outdoor spaces and buildings, transportation and streets, health and wellness, social participation, inclusion and education opportunities, volunteering and civic engagement and job opportunities.

The survey results, together with an analysis of current community services and gaps, will allow the institute to make specific and strategic recommendations to KIPDA. If adopted, these recommendations are designed to ensure that older adults and individuals with disabilities have their immediate social service needs met while more broadly enabling them to lead lives of dignity and independence.

Anyone living in the designated counties is invited to complete the Community Needs Assessment Survey. The more people that participate, the more likely service gaps can be addressed. Older adults, caregivers, and persons with disabilities are especially encouraged to participate in this research study. Survey participants do not have to be recipients of KIPDA services.

The assessment can be found online or by calling 502-852-8953. The institute can provide a paper copy upon request or at senior centers within the seven counties. The deadline to complete the assessment is Feb. 1, 2018.

For more information, visit www.optimalaginginstitute.org/kipda or contact Dr. D’Ambrosio at joe.dambrosio@louisville.edu or 502-852-7811.

University of Louisville Hospital opened a new center today to treat hepatitis C, a particular problem in Kentucky, which has the highest infection rate in the country.

A ribbon-cutting and open house marked the UofL Hospital Hep C Center’s official opening Wednesday morning, with the first patients scheduled later in the day.

“While Kentucky has the highest rate of new hep C cases in the U.S., few places exist here for treatment,” said Barbra Cave, a family nurse practitioner specializing in gastroenterology and hepatology who leads the center. “This is a much-needed service in the community.”

In the past, treating hepatitis C was difficult. It involved a triple therapy with interferons that lasted almost a year, with multiple side effects. Not everyone was a candidate for treatment. Doctors found it challenging, and some patients opted to not get treated at all.

“Many patients were scared off by treatment, knowing it was going to be hard,” Cave said. “Maybe they saw a friend go through it. But we want them to know it’s not hard anymore. We can help so many people.”

Today, treatment is one pill, once a day, for 8-12 weeks – with minimal side effects, said Ashutosh Barve, M.D., Ph.D., the center’s medical director and a gastroenterologist with the hospital and UofL Physicians. The center also uses FibroScan, which allows staff to perform a non-invasive assessment of the liver without a biopsy.

“This is truly a success story of modern medicine,” he said. “We went from discovering the basic science of the disease in the late ‘80s, early ‘90s, to finding a cure in 2014.”

Up to half of patients who have it may not know they are infected, Cave said. The U.S. Centers for Disease Control and Prevention has recommended screening for all baby boomers.

“People may carry the disease for decades before they have symptoms,” she said.

Hepatitis C is a blood-borne illness. It may have been contracted from a blood transfusion prior to 1992, contaminated tattoo equipment or IV drug use. Older veterans are particularly at risk due to the use of the old “jet gun” vaccinators by the military and combat injuries, Cave said.

Contaminated dental equipment can also spread hepatitis C, and the disease can be passed from mother to baby.

“The virus can live on a surface for weeks, if not sterilized properly,” Cave said.

Though hepatitis C is now easily curable with proper treatment, the disease can cause major complications if left untreated. It can cause cirrhosis of the liver or liver cancer. Barve, who also directs the Liver Cancer Program at the UofL School of Medicine, said hepatitis C is a leading cause of liver transplant.

Hepatitis C may predispose those infected to diabetes and depression, and it has an association with joint pain, regardless of the amount of liver damage.

The new center will see patients every weekday, and the hospital is expecting 2,000 patient visits per year, with space to expand as volume grows. 

How would scientists go about encouraging interest in their field and educating the public about science? Members of the Louisville chapter of the Society for Neuroscience found more than 30 ways to accomplish that goal, developing interactive exhibits at the Kentucky Science Center, speaking about scientific topics at public events and organizing seminars to encourage K-12 students’ interest in science and more.

For their work, the Louisville group was named the 2017 chapter of the year by the National Society for Neuroscience (SfN) earlier this month at the organization’s annual meeting in Washington, D.C.

The Society for Neuroscience is an organization of nearly 38,000 basic scientists and clinicians in more than 90 countries who study the brain and nervous system. The Louisville SfN chapter includes nearly 300 members, about 280 of whom are faculty, staff and students at the University of Louisville. Members also represent Bellarmine University, Morehead State University and Northern Kentucky University.

The SfN presents its Chapter-of-the-Year Award in recognition of a chapter’s accomplishments in outreach to the public, providing neuroscience resources for K-12 education and advocacy for issues related to research and science.

The Louisville chapter organized or participated in more than 30 events between June 2016 and July 2017 related to this mission. Members hosted 25 minority high school students interested in health professions for a tour at UofL, held a seminar to encourage middle school girls’ interest in STEM-related careers, developed “Brain Days:  An Interactive Neuroscience Experience” at the Kentucky Science Center, and helped organize the local March for Science in Louisville. The club estimates that through these and other events, 171 volunteers helped educate more than 5,000 people about the field of neuroscience.

In addition to the chapter award, the group’s outgoing president, Kristofer K. Rau, Ph.D., earned the organization’s Next Generation Award for junior faculty for his efforts to share neuroscience with the public throughcommunication, education and outreach activities. Rau, a senior research associate in the UofL Department of Anesthesiology, spearheaded community outreach efforts for SfN’s Louisville chapter designed to increase science education and literacy focused on nervous system function and careers in neuroscience research. Rau helped to establish adult education programs, initiated neuroscience awards at regional science fairs, and prepared materials and mobilized volunteers for a walk to end multiple sclerosis.

The Louisville SfN chapter will receive $3,000 for the two awards.

November 30, 2017

Putting action and investment behind commitment is evident at University of Louisville Hospital with two new technologies put into place that advance the goal of controlling infection.

The hospital, in conjunction with UofL’s James Graham Brown Cancer Center, recently renovated and enlarged its Bone Marrow Transplantation Unit, including the installation of all new copper fixtures that utilize the metal’s antimicrobial properties to control infection. UofL Hospital is the first facility in the Kentuckiana region to install the new fixtures.

The hospital also is the first in the area to begin using a new hand hygiene system that reminds staff to wash their hands, if they forget. Staff members wear a badge that displays a red, yellow or green hand that automatically communicates compliance status to patients, reassuring them they are safe. The system collects compliance data that can be shared with staff and administrators.

These efforts are not isolated events but are part of a dedicated effort to improve patient safety, said University Medical Center (UMC) Interim President/CEO Ken Marshall. UMC is the parent organization that has operated the hospital and cancer center since July 1.

“While we meet or exceed national standards of care once a hospital-acquired patient infection has been identified, our opportunity is around earlier recognition to prevent infection,” Marshall said. “To this end, we have enhanced the use of tools available to us through new technologies and have put in place a continual education and training process.”

While it is too soon to have verified data on the results of these efforts, hospital leaders are confident that the new measures will enable the hospital to increase its rates of infection control and reduce the incidence of hospital acquired infections (HAIs) in patients.

“HAIs can happen in any health care facility,” said UofL Hospital Chief Medical Officer Jason Smith, M.D., Ph.D., including hospitals, ambulatory surgical centers, long-term care facilities and others. “They are caused by bacteria, fungi, viruses or other less common pathogens. The new systems installed at UofL Hospital will have a significant impact in reducing the incidence of HAIs.”

HAIs can be a cause of illness and death, and they can have emotional, financial and medical consequences. At any given time, about 1 in 25 inpatients has an infection related to hospitals or other health care facilities in the United States. These infections lead to the loss of tens of thousands of lives and cost the U.S. health care system billions of dollars each year.

“As front-line care providers, our nurses know better than anyone about the toll that HAIs can have on patients and their families,” said Chief Nursing OfficerShari Kretzschmer, R.N. “Nurses at UofL Hospital and James Graham Brown Cancer Center play a key role in preventing the spread of HAIs and we are excited to embrace these new tools introduced for the first time in our region to help strengthen infection control.”

The effort was a worthwhile investment, Marshall said. “On July 1, a health care resource that has been vital to this community for nearly 200 years entered a new era of service to the people of Metro Louisville and Southern Indiana,” he said. “Our necessity to change, improve and grow is mandatory, and we will work to implement whatever investment is needed to achieve that growth.”

“Incorporating new technology shows our commitment to providing a safe environment for patient care,” said Director of Infection Prevention and ControlSarah Bishop, A.P.R.N., at UofL Hospital. “I’m proud to work for an organization that is an early adopter of these emerging technologies.”

The new technologies are CuVerro Bactericidal Copper Surfaces and the BioVigil Hand Hygiene System.

About CuVerro Bactericidal Copper Surfaces

Copper has been known to have inherent bactericidal properties for thousands of years. While its exact mechanism of action is not yet fully known, research suggests that copper surfaces affect bacteria in two sequential steps: the first step is a direct interaction between the copper surface and the bacterial outer membrane, causing the membrane to rupture. The second is related to the holes in the outer membrane through which the cell loses vital nutrients and water, causing a general weakening of the cell. CuVerro works with manufacturers to leverage this quality into the development of products that kill almost 100 percent of the bacteria that cause HAIs within two hours of contact.

CuVerro and JRA Architects of Louisville partnered with UofL Hospital in the renovation of the Bone Marrow Transplantation (BMT) Unit. Patients requiring BMT take anti-rejection drugs that compromise their immune systems, making them highly susceptible to bacterial infection. The copper surfaces on the fixtures in the BMT unit are an added protective measure against infection.

The surfaces are found in virtually every fixture touched by human hand: patient room sinks, bathroom sinks, faucets, electrical switch plates, door hardware, cabinetry hardware and shower safety grab bars. There are approximately 20 separate surfaces in each of the 16 rooms in the unit plus another 10-20 fixtures in each hallway, common area, office and treatment room.

About the BioVigil Hand Hygiene System

The BioVigil electronic hand hygiene solution reminds hospital staff to perform hand hygiene if they forget. BioVigil also visually communicates to and reassures patients and families that hand hygiene has been performed via a colored hand displayed on a badge worn by health care workers. Green confirms that hand hygiene has been performed. Yellow is a reminder that staff must wash their hands, and red means that staff must stop and wash their hands. To comply with hand hygiene, users apply sanitizer and place their hand over the badge, which detects the alcohol from the sanitizer.

Hand hygiene activities are automatically recorded by a badge and then securely downloaded to a cloud-hosted database once the badge is returned to a base station. The hospital retrieves monitoring and compliance reports through the system’s data suite or via email.

The system makes it easy for health care professionals to comply with hand hygiene, empowers patients to take an active role in their care and helps hospitals combat HAIs. The technology works with all sanitizer and soap products. It has been introduced in nine units thus far in UofL Hospital and will continue to be introduced to other units over time.

The system is manufactured by BioVigil Healthcare Systems Inc. of Ann Arbor, Mich.

#WeAreUofL

CuVerro, with brand headquarters in Louisville, is manufactured by GBC Metals LLC, doing business as Olin Brass, a wholly owned subsidiary of Global Brass and Copper Inc. which is a subsidiary of Global Brass and Copper Holdings Inc., the leading manufacturer and distributor of copper, copper‐alloy and bactericidal copper sheet, strip, plate, foil, rod, ingot and fabricated components in North America and one of the largest in the world. GBC Metals engages in the melting, casting, rolling, drawing, extruding and stamping of specialized copper and copper alloys finished products from scrap, cathode and other refined metals (OB-0047-1711). For more information visit cuverro.com or contact cuverro@olinbrass.com.

The University of Louisville continues to lead in educating future physicians to provide the best possible health care for patients who are lesbian, gay, bisexual, transgender (LGBT), gender nonconforming and those born with differences in sex development (DSD). UofL’s eQuality Project, the initiative to embed training in the care of these patients throughout its medical school curriculum, has won the 2016-2017 Innovation in Medical Education Award from the Southern Group on Educational Affairs (SGEA).

The SGEA presents a single Innovation in Medical Education Award each year for a good, replicable idea for other medical education institutions to consider. Chosen over three other nominees, UofL’s eQuality Project won thanks to the timely topic and the unique but practical approach, according to Karen “Sam” Miller, Ph.D., director of graduate medical education and research at UofL and chair of SGEA, a regional subgroup of the Association of American Medical Colleges (AAMC).

In 2014, UofL became the pilot program for the development of curriculum to incorporate competencies published by the AAMC related to provision of care for LGBT and DSD individuals.

“Every patient deserves to be cared for with respect and competence,” said Toni Ganzel, M.D., M.B.A., dean of the UofL School of Medicine. “The faculty and staff members who have devoted so many hours in the eQuality Project have made it their mission to provide the best education for our future physicians in the care of LGBTQ patients. I am extremely proud of their work and pleased that the SGEA is recognizing it as a model for other institutions.”

Susan Sawning, M.S.S.W., director of undergraduate medical education research, and Laura Weingartner, Ph.D., research manager, were recognized for the award at the SGEA Business Meeting during the 2017 AAMC Learn, Serve, Lead conference in Boston earlier this month. The award will be presented formally at the SGEA Regional Conference in April 2018 in Jackson, Miss.

“This has been a beautiful team effort,” Sawning said. “I am most proud that our LGBTQ community is feeling empowered and better cared for, and that makes it all worth it.”

The project included Sawning, Weingartner and other members of the eQuality Steering Committee:  Chaz Briscoe, M.A., Dwayne Compton, M.Ed., Amy Holthouser, M.D., Charles Kodner, M.D., Leslee Martin, M.A., David McIntosh, Ph.D., Emily Noonan, M.A., M. Ann Shaw, M.D., M.A., Stacie Steinbock, M.Ed., and Jennifer Stephens, B.A.

The AAMC is the not-for-profit association representing all 145 accredited United States and 17 accredited Canadian medical schools; nearly 400 major teaching hospitals and health systems, including 51 Department of Veterans Affairs medical centers; and nearly 90 academic and scientific societies. Through these institutions and organizations, the AAMC represents 148,000 faculty members, 83,000 medical students, and 110,000 resident physicians.

#WeAreUofL

November 28, 2017

NOTE: Watch a video of Dr. Coldwell talking about the new Discovery IGS 740 system at UofL Hospital here. 

University of Louisville Hospital is the first in the region to install and use a new imaging system that is more accurate, faster and safer than traditional units.

“This is the most advanced piece of arteriographic equipment in the world at the moment,” said Douglas Coldwell, M.D., Ph.D., director of vascular and interventional radiology and interventional oncology at UofL Hospital and a professor of radiology and bioengineering at the UofL School of Medicine. “And we are the only ones to have it in this area. This really is a big deal.”

The Discovery IGS 740 provides exceptionally detailed, 3-D images in real time of patient anatomy, which Coldwell said is invaluable in trauma cases.  Doctors can accurately determine the site of bleeding and close it off, saving lives.

He said Discovery’s laser-guided tools give doctors the ability to be much more precise in treatment.

“With this new system, we’ve taken a leap forward in patient care in this community and region,” Coldwell said.

With its unique mobile platform, the Discovery has the power and capability of traditional fixed imaging units, but rides on the floor, moving around the patient as necessary, free of interference from fixed floor or ceiling structures. At the touch of a button on bedside controls, doctors can use its laser guidance mechanism to precisely position it just about anywhere for the best possible images of parts of the anatomy. It can then be moved aside so medical professionals can work efficiently and have unobstructed access to patients.

Its exceptionally high-quality images allow doctors to perform delicate procedures such as blood vessel interventions with accuracy and confidence, Coldwell said.

“It allows us to get in, treat a patient and do it without complications, and have a better patient outcome,” he said. Even arteries can be looked at in 3-D, allowing doctors to “plan exactly where we’re going to go in treatments,” such as for stent and angioplasty.

Its large digital detector also gives doctors the ability to see more in a single exam with fewer X-ray images, and fewer injections of contrast dye, and carries just a fraction of radiation of traditional units, making it much safer for patients and staff.

“Everyone is concerned about radiation,” he said. “With this equipment, we get 1/10^th to 1/100^th of the radiation of other units.”

The Discovery unit’s precision makes it perfect for use in patients at the UofL James Graham Brown Cancer Center.

“It allows for amazingly targeted radiation,” Coldwell said.

Tumors can be treated by injecting radioactive beads the size of talcum powder particles into them via arteries. “This requires precise placement, which we can do with the Discovery system,” Coldwell said. “A very high dose of radiation can be given to the tumor, while sparing the surrounding tissues. That means fewer side effects for patients.”

The equipment has its own dedicated room at the hospital. Mike Goode, the hospital’s director of imaging and neurodiagnostic services, said installation was finished last month at a cost of around $2 million, including precision leveling of seamless floors to hold the sensitive, heavy equipment, which took nearly a month.

Doctors have been seeing patients with the system for a few weeks, and the difference is profound, Coldwell said.

“We’re pretty excited about it,” he said. “It’s a game-changer.”

Researchers in the University of Louisville Department of Pharmacology and Toxicology spoke with Future Problem Solvers this week from two rural Kentucky high schools in hopes of prepping them for the district level academic competition.

Students from Adair County High School in Columbia, Ky. and Russel High School in Ashland, Ky. visited UofL’s Wise Laboratory of Environmental and Genetic Toxicology researchers. They toured labs and participated in a seminar on toxic materials - the topic for the district challenge of Future Problem Solving, a program of the Kentucky Association for Academic Competition that encourages critical thinking.

“Science unlocks the secrets of the universe and the keys to technology, including current ideas and those yet to be imagined,” said John Pierce Wise, Sr., Ph.D., professor of pharmacology and toxicology and University Scholar. “Engaging young people in science opens their hearts and minds to a whole new world of imagination, discovery and possibility, and starts them on a journey that will transform both their own lives and society as a whole." 

Tayler Croom-Perez, Ph.D., postdoctoral associate and Rachel Speer, M.S., doctoral candidate, explained the work of the Wise lab, which embraces a “One” environmental health philosophy.

“The concept considers how human health, animal health and ecosystem health are intertwined and interdependent, such that there is only “one” health,” Speer said.

Wise lab researchers study and compare human health with that of whales, alligators and sea turtles along with ecosystem changes. The goal, Speer says, is to better understand the impact on health, to discover novel adaptations in animals that may give insights into human health, and to use human health data in an effort to conserve wildlife and protect the ecosystem.

The toxicology investigators also study how environmental chemicals convert normal cells into tumor cells that cause cancer. In this work, scientists focus on structures inside cells called chromosomes, which contain the cell’s DNA. The researchers study how chemicals damage DNA and interfere with the ability of cells to repair that damage.

Nov. 30, 2017

License plates supporting the Alzheimer’s Association are available for purchase in Kentucky, making the Bluegrass the first in the United States to offer a specialty plate for Alzheimer’s.

In 2016, the University of Louisville’s Institute for Sustainable Health & Optimal Aging provided underwriting for the final applicants to help move the plates into production and raise awareness of the disease that affects nearly 70,000 Kentuckians.

“Our institute is honored to support the Alzheimer’s Association and all Kentuckians who have been touched by Alzheimer’s disease. This license is a powerful symbol of our enduring love for those affected by Alzheimer’s, our unwavering support for their family members, and our commitment to working with our communities and the Alzheimer’s Association to end Alzheimer’s,” said Dr. Anna Faul, Ph.D., executive director of the institute. 

“The Alzheimer’s specialty plate has been a dream of ours for years,” said DeeAnna Esslinger, executive director of the Alzheimer’s Association Greater Kentucky and Southern Indiana chapter. “Not only will the plates be a very visible reminder of those suffering with Alzheimer’s, but their sale will also help raise funds for local education initiatives.”

The license plate features a forget-me-not flower on a purple background with the words: ‘Honor. Remember. Care. End Alzheimer’s.’ Drivers may purchase the plate when renewing their tags at any county clerk office. Specialty plate purchasers also can give an additional $10 donation to help fund Alzheimer’s awareness and education activities in Kentucky.

For information visit: https://www.alz.org/kyin/

About the Alzheimer’s Association Greater Kentucky and Southern Indiana Chapter:

The Greater Kentucky and Southern Indiana Chapter of the Alzheimer’s Association provides service and education to 125 counties across greater Kentucky and southern Indiana. Over 5 million Americans are living with the disease and more than 90,000 of them reside in our service territory. Services provided include education programs for persons with dementia, caregivers, professionals and the general community as well as support groups and a 24/7 Helpline. Further, the Chapter advocates at the state and national level of government for research and support services on behalf of the people of Kentucky who suffer from Alzheimer's disease.

Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., professor and distinguished university scholar in UofL’s Department of Anatomical Sciences and Neurobiology, led a team of researchers who have described the protein’s critical role in the growth and repair of skeletal muscles, both in post-natal development and in the regeneration of injured adult muscles.

UofL post-doctoral fellows Sajedah M. Hindi, Ph.D., and Yann S. Gallot, Ph.D., along with Jonghyun Shin, Ph.D., formerly of UofL and now with Yonsei University in South Korea, conducted the research in Kumar’s lab. It is published today in Nature Communications.

In the formation of muscle, specialized progenitor or stem cells multiply. They then differentiate into preliminary muscle cells called myoblasts. The myoblasts fuse together and subsequently form muscle fiber. Using animal models, the UofL researchers worked with both neonatal cells and adult cells to determine that MyD88, a key signaling protein in the human body, is required in sufficient quantity for myoblasts to fuse.

Hindi believes that MyD88 eventually may be used to improve the effectiveness of therapies using donor cells for the treatment of degenerative muscle disorders such as muscular dystrophies.

“Since MyD88 promotes only the fusion of myoblasts without affecting their proliferation or differentiation, enhancing the levels of MyD88 levels could be a means to enhance engraftment of exogenous myoblasts in cellular therapies,” Hindi said.

Kumar adds that increasing the expression of MyD88 could be used in the treatment of rhabdomyosarcomas, cancerous tumors that develop in skeletal muscles and often affect children.

“We are investigating whether augmenting the levels of MyD88 inhibits growth of rhabdomyosarcoma in animal models,” Kumar said. “Finally, we are investigating whether the loss of MyD88 is responsible for the diminished muscle regeneration capacity in the elderly.”

Research in Kumar’s lab focuses on understanding the molecular and signaling mechanisms that regulate the acquisition and maintenance of skeletal muscle mass. For the past eight years, they have been investigating the proximal signaling mechanisms that regulate skeletal muscle atrophy, regeneration and muscle hypertrophy, in addition to the signaling mechanisms that regulate self-renewal and differentiation of satellite cells in myogenic lineage.

In 2015, research from Kumar and Hindi published in the Journal of Clinical Investigation described the role of TNF receptor-associated factor 6 (TRAF6) in maintaining satellite cells and their ability to regenerate injured muscles. Just ten days later, research from the lab published in Nature Communicationsrevealed how the protein transforming growth factor-ß-activated kinase 1 (TAK1) is vital in the self-renewal of satellite stem cells.

Research reported in this press release was supported by the National Institute of Health grants AR068313, AR059810, and AG029623 to Ashok Kumar and AR069985 to Sajedah M. Hindi.

November 20, 2017

With a scarcity of lungs available for transplantation, the use of lungs from donors older than age 60 has been shown to achieve reasonable outcomes and should be considered as a viable option, according to research published online Thursday in The Annals of Thoracic Surgery.

"The availability of suitable donor lungs for transplantation continues to be a major obstacle to increasing the number of lung transplants performed annually, and this study demonstrated that reasonable outcomes are possible with the use of advanced age donors," said William Micah Whited, M.D., of the University of Louisville Department of Surgery. "Research such as this that explores the means of expanding the donor pool is of critical importance."

Whited, along with senior author Matthew Fox, M.D., of the Department of Cardiovascular and Thoracic Surgery and other colleagues from UofL, queried the United Network of Organ Sharing thoracic transplant database to identify lung transplant recipients age 18 years or older.

Between January 2005 and June 2014, 14,222 lung transplants were performed. Of these lung transplant recipients, 26 percent were age 50 years or younger, with 2 percent receiving lungs from donors older than age 60. Among this group of younger patients who received older donor lungs, there was no significant difference in five-year survival when compared to patients who received lungs from younger donors.

The researchers also examined the impact of double versus single lung transplant on long-term survival, finding that younger patients who received older donor lungs experienced much better outcomes when a double versus a single transplantation was performed.

The study showed that in younger patients who received a single lung transplant using organs from older versus younger donors, there was a lower five-year survival: 15 percent versus 50 percent. However, with a double lung transplant, there was no significant difference in five-year survival: 53 percent versus 59 percent.

“Ideal donor” criteria vary by hospital, but the researchers said that the criteria generally consist of brain death, age less than 45 to 50 years, minimal smoking history, and no evidence of pneumonia or trauma. Donor organs that do not meet all of the ideal donor criteria are sometimes accepted, but not always.

Whited said that while the use of extended criteria donor lungs varies from program to program, most surgeons should be willing to accept non-ideal donors, especially those who are older but otherwise good candidates.

"The vast majority of potential donors do not meet the relatively strict donor criteria," he said. "As a result, we need to continue exploring options that would expand the donor pool and more aggressively utilize extended criteria donors. Much like the general population, the donor pool has continued to grow older. Now more than ever, we have to rely on older donors."

The U.S. Organ Procurement & Transplant Network (OPTN) reports that 1,399 people currently are waiting for a lung transplant in the United States. The overall median waiting time for candidates on the wait list is four months, while more than 200 people die annually waiting for a lung transplant, according to an OPTN report.

Leading experts in reproductive endocrinology, Kelly Pagidas, M.D., and Miriam Krause, M.D., will address issues and possibilities surrounding parents’ ability to determine specific genetic traits in their children at the next Beer with a Scientist event, Wednesday, Nov. 15.

Pagidas and Krause will answer the question:  Can we really engineer our children? They also will provide an overview of current genetic testing available with in-vitro fertilization and the ethical considerations that go along with that capability.

Pagidas practices with Ob/Gyn & Women’s Health at UofL Physicians and is a professor and the division and fellowship program director of the Division of Reproductive Endocrinology and Infertility in the UofL Department of Obstetrics, Gynecology & Women’s Health. Krause practices with Fertility and Endocrine Associates.

The talk begins at 8 p.m. on  Wednesday, Nov. 15, at Against the Grain Brewery, 401 E. Main St. in Louisville. A 30-minute presentation will be followed by an informal Q&A session.

Admission is free. Purchase of beer, other beverages or menu items is not required but is encouraged.

Organizers add that they also encourage Beer with a Scientist patrons to drink responsibly.

UofL cancer researcher Levi Beverly, Ph.D., created the Beer with a Scientist program in 2014 as a way to bring science to the public in an informal setting. Once a month, the public is invited to enjoy exactly what the title promises:  beer and science. For more information and to suggest future Beer with a Scientist topics, follow Louisville Underground Science on Facebook.

Beer with a Scientist will take the month of December off. Dates are set for the first quarter of 2018:  Jan. 17, Feb. 21, Mar. 14.

The University of Louisville has received a $6.7 million grant from the National Institutes of Health to become one of fewer than two dozen Superfund Research Centers across the United States.

The five-year grant comes after a 20-year effort by the university to secure Superfund money for environmental study and will establish a new, multidisciplinary center at UofL that will support the federal Superfund Hazardous Substance Research and Training Program.

UofL was one of five new Superfund Research Center sites funded in 2017, bringing the number across the nation to 23, including such institutions as the Massachusetts Institute of Technology, Columbia University and Duke University.

“The University of Louisville is joining an elite group of research enterprises in this growing field of study examining the impact of environmental determinants to health conditions,” said Gregory Postel, M.D., interim president of the University of Louisville. “The work performed here will impact the field for generations to come, not only from the research findings that come from the program, but from the next generation of researchers who will be educated and trained.”

“This is a very prestigious grant for the university and will help raise the awareness of environmental issues as they relate to health, and train the next generation of environmental scientists,” said Sanjay Srivastava, Ph.D.,a professor and researcher in cardiovascular medicine at the UofL School of Medicine who will lead the project.

Researchers will study how chemical exposures, particularly to chemicals known as volatile organic compounds (VOCs), contribute to the incidence, prevalence and severity of cardiometabolic disease as it relates to cardiovascular disease, type 2 diabetes, obesity and fatty liver disease, all big problems in Kentucky.

The Superfund program, created in 1980, is part of a federal government effort to clean up land in the U.S. that has been contaminated by hazardous waste, and identified by the U.S. Environmental Protection Agency as a potential risk to human health or the environment. The program was started in part by the discovery of a waste site near Louisville in Bullitt County. Known as the “Valley of the Drums,” the site contained thousands of steel drums full of chemical waste that accumulated over decades.

Currently, there are hundreds of Superfund sites across the country, and Louisville has one near the Rubbertown industrial area along Lees Lane in the western part of the city.

The grant to UofL comes through the National Institute of Environmental Health Sciences Superfund Research Program, which funds university-based research on human health and environmental issues related to hazardous substances. The program’s goal is to understand the link between chemical exposure and disease, reduce that exposure and better monitor the effects on health.

While the government tried to make Superfund sites safe, it was not completely known exactly how toxic some of that waste was, or how it could exacerbate diseases. Waste at Superfund sites includes such substances as industrial solvents, pesticides, metals, dry-cleaning solvents, paints, wood preservatives, cleansers, disinfectants and gasoline and other petroleum products that generate VOCs such as butadiene, trichloro ethylene, benzene, acrolein, vinyl chloride, and formaldehyde.  When disposed of together, these substances can react and form compound chemicals that are even more toxic.

“The task of cleaning up those sites proved easier said than done,” said Srivastava, who also is a Distinguished University Scholar at UofL.

In its heyday, Rubbertown was a booming industrial site with multiple factories and plants. Today, manufacturing in the area is down about 90 percent and the EPA closed the Superfund site to waste disposal about five years ago, satisfied that the waste disposed of there no longer posed a threat. But residents have continued to complain about chemical odors from the site, and the EPA has made multiple visits back as it considered reopening the site for remediation, Srivastava said.

Studies already have associated certain chemicals with heart disease and metabolic disorders. Excessive rates of type 2 diabetes and stroke have been found in an evaluation of 720,000 people living within a half-mile of 258 Superfund sites associated with excessive VOCs in drinking water.  “There is strong evidence that insulin resistance, type-2 diabetes, fatty liver disease and cardiovascular disease are associated with environmental exposures” Srivastava said.

UofL’s Superfund Research Center will focus on residents around the Lees Lane Landfill, a 112-acre landfill in Southwest Louisville. The site was used for a quarry in the 1940s and 1950s and was used as a landfill through 1975. The EPA placed the site on the Superfund program in 1983 because of contaminated ground water, surface water, soil and air resulting from landfill operations. Steps were taken to clean up the site and the EPA removed the site from the National Priorities List in 1996. However, the most recent estimates were inconclusive regarding remedy protectiveness, Srivastava said.

The Superfund team will measure pollutant exposure at the site, and compare pollutant levels at this site with those in the Rubbertown site with its multiple factories and plants. Nearly 38,000 people live within three miles of the site. Using data from the U.S. Census Bureau and death records from 2005-2009, UofL researchers have observed a 48 percent higher cardiovascular mortality in 26 neighborhoods around Rubbertown than in nearby Louisville areas.

The UofL team hopes to enroll 500 participants from three geographic areas in the project: one near the Superfund site on Lees Lane; one farther away, but still in Rubbertown; and one not nearby, in Oakdale. Researchers will set up continuous air monitoring at the sites, as well as mobile monitoring in different areas to help determine how far the level of gaseous pollution from the ground extends.

They will collect current health and demographic data and medical history, and look for evidence of chemical exposure in blood, urine and other samples. Participants’ blood chemistry, obesity and cardiovascular and liver function will be monitored after 18 months and 36 months. The team also will study the cardiometabolic effects of VOCs in animal models.

The other part of the project will focus on developing sensors for measuring VOCs in the air and constructing a land-use model to decrease ambient VOCs. The project also will test whether planting trees – known to help reduce the effect of exposure to toxic particles and VOCs in the air and soil – would improve the health of residents in the Oakdale area under the Green Heart project, launched last month. 

Gretta Walters is “truly the mom when mom can’t be there.”

A nurse at University of Louisville Hospital, she cares for infants in the neonatal intensive care unit of the Center for Women & Infants. And she can say something a lot of people can’t say – she never dreads going to work.

 “I get to care for babies,” she said. “And I love UofL Hospital, it’s a warm, caring place to work.”

Four years ago, Gretta’s love for what she does changed the life of one of her patients, and her own. Tabby Cooper’s son was born at 26 weeks via an emergency Cesarean section. Gretta was there, doing her job, wrapping Sulli Cooper’s tiny body and placing him in an incubator, where he would live the first two months of his life.

Twenty-three weeks’ gestation is considered the age at which a baby is viable. Little Sulli beat that by three weeks, and he had a long road ahead of him. A few hours after he was stabilized, Gretta came to talk with Tabby.

“She gave me two pictures of my baby boy and told me everything about him,” Tabby said. “And she warned me of the roller coaster ride I was about to endure.”

But she would not have to ride that roller coaster alone. Gretta was there, every step of the way.

“The first few days were agonizing, when I looked at this tiny baby and I wasn’t able to help him,” Tabby said. “I was so afraid to put my hands in the box. He was so fragile. One day, Gretta asked if I’d held him. When I said no, she said ‘We’ll change that.’ She had me place my hands inside his incubator and placed his tiny two-pound body in my hands. She asked if two pounds was heavier or lighter than I imagined. He was heavier than I thought.”

Then one day, Sulli took a turn for the worse, and became very ill.

“Gretta stood by my side, holding me as I cried, not knowing what the future held,” Tabby said. “She sat across from me in the dark as I sat at his bedside, because he was not going to be without his mommy while he was sick.”

Gretta often brought Tabby magazines or books, trying to give her a break.

Eventually, he recovered, and it was finally time for him to go home. “She showed so much love to our tiny baby, and she also cared for me and my husband,” Tabby said.

But once Sulli left the hospital, that wasn’t the end of the family’s time with Gretta. The experience had forged a bond between the two, who became close friends, taking walks at the zoo or park, talking on holidays and sharing stories.

“We do a lot of things with the kids, who I love seeing,” Gretta said. “We spent months together, almost every day and night. It made us close.”

Three years later at UofL Hospital, Gretta was back at Tabby’s side again when Tabby’s triplet daughters came into the world – eight weeks early. “Once again, Gretta reminded me of the crazy ride we were in for. And there she was, encouraging me and my husband, just like before,” Tabby said.

This May, Gretta will have her own special moment as she gets married. Her flower girls will be none other than Tabby’s daughters, who were born as Gretta and her fiancé had just met.

“We talked through the night, and I told her about him,” Gretta said.

Tabby says she’ll never be able to thank Gretta enough. She recently nominated her for a DAISY Award for exceptional nurses from The DAISY Foundation.

“She showed my son, daughters and all the infants she cared for so much love and affection. She provided a tremendous amount of support to the patients, parents and their families. She is truly the mom when mom can’t be there. She is an extraordinary nurse.”

Gretta, who is from Brandenburg, Ky., said she always knew she’d be a nurse or a veterinarian from the time she was 13 years old. She doesn’t have her own children, but caring for others comes naturally for her.

“I love being a nurse,” she said. “It’s a challenge, as you never know what you are going to get. And I love being a nurse at UofL Hospital.”

She said the staff is like a second family, working as a team and spending long days and nights together, and supporting each other during rough times.

“It’s like home,” she said. “I think our patients feel that.”

Kentucky ranks among the worst states for access to quality health care, and 96 of its 120 counties are medically underserved. Educating health-care providers within the state is vital to combating the shortage of health workers and is the heart of the mission of Area Health Education Centers (AHEC).  Kentucky AHEC has been awarded $4.12 million in continued funding from the federal Health Resources and Services Administration (HRSA) to continue that mission through Aug. 2022.

Administered by the University of Louisville School of Medicine in collaboration with the University of Kentucky College of Medicine, Kentucky AHEC has worked to improve Kentuckians’ access to health care since 1985. Kentucky AHEC is composed of eight centers that promote healthy communities and health-care delivery in the state’s regional service areas by increasing the number of health-care workers of all disciplines, particularly in underserved areas.

“The AHEC centers contribute to the education of health professionals at UofL and at other institutions throughout Kentucky. Having an adequate number of well-trained, dedicated health professionals is a vital component to reducing health disparities, increasing access to health-care and improving the health of all Kentuckians,” said Gregory Postel, M.D., interim president of the University of Louisville. “This renewed funding is assurance that these programs will continue to support health education in the Commonwealth.”

Since its inception, Kentucky AHECs have facilitated the training of medical students in primary care, in many cases, introducing the students to issues faced by patients in underserved communities. All third-year students in the UofL School of Medicine complete a four-week clinical rotation in family medicine in rural or urban underserved communities throughout the state. The Kentucky AHEC program also provides education and rotations for nursing and dental students.

“Students gain a deeper understanding of the needs of the patients by working in these communities. It encourages then to consider practicing primary care in rural or urban underserved communities,” said Kelli Bullard Dunn, M.D., vice dean for community engagement and diversity at UofL, Kentucky AHEC program director and the principal investigator of this HRSA award.

To facilitate training, AHEC staff work with the Schools of Medicine, Dentistry and Nursing to identify physicians and other professionals to coordinate students’ rotations in their communities. This provides a framework for the students to complete rotations in clinics, medical offices and community hospitals across the Commonwealth.

“This is a way for health-professions students to come out and serve in rural and underserved communities where they are exposed to different cultures and the practice of medicine without the innovative technologies available at the health sciences campuses. They get to see real medicine, real people,” said Brenda Fitzpatrick, director of the Northwest AHEC, based at the Family Health Center in Louisville’s Portland neighborhood.

In addition to educating health-professional students, AHECs in each region develop programs that further their mission in ways best suited to their communities.

For Fitzpatrick, that is developing a true pipeline of health-care professionals, from physicians and dentists to nurse practitioners, physician assistants, nurses, nurse’s aides, bioengineers and computer technology professionals.

“While HRSA encourages AHECs to promote careers in the health professions to high school students, we take that a step further and work with middle school students,” she said. “By the time they reach eighth grade, it may be too late.”

Fitzpatrick adds that the Northwest AHEC collaborates with several medical magnet schools in Jefferson County to help students obtain certifications during high school.

“This will get them in the workforce sooner and allow them to then continue their education and move on up the chain.”

In the latest round of program funding, HRSA has instructed AHEC programs to encourage patient-centered medical homes, which coordinate patients’ care in a single office, improving overall health-care delivery and reducing costs.

Another new directive from HRSA is the development of the AHEC Scholars program. Each center will instruct 15 -25 health-profession students from a variety of disciplines in interprofessional education, behavioral health integration, social determinants of health, cultural competency, practice transformation and current and emerging health issues. Interprofessional education fosters collaboration among physicians, nurses, social workers, allied health and other providers.

“In a time of significant federal cutbacks, we were pleased to receive funding under HRSA’s extensively revised criteria,” Bullard Dunn said.

In addition to the federal funding, Kentucky AHEC is supported by Kentucky General Assembly appropriations, UofL and UK. AHEC is part of UofL’s Signature Partnership, a university effort to enhance the quality of life and economic opportunity for residents of West Louisville.

November 9, 2017

Research published online this week by the Proceedings of the National Academy of Sciences could lead to therapeutic advances for recovery from injury and diseases affecting the central nervous system. Bart Borghuis, Ph.D., assistant professor in the University of Louisville Department of Anatomical Sciences and Neurobiology, worked with researchers in Idaho and Puerto Rico on the research, which stimulated the formation of new neural connections in adult retinal cells through genetic modification.

Typically, adult neurons cannot make new synaptic connections as easily as developing neurons. That limits the potential for recovery from injury to the brain and spinal cord. One type of neurons in the retinas of mice, OFF-type retinal bipolar cells, has the unusual ability to make new connections into adulthood. Under normal conditions however, these cells only develop new connections with a few cells and within a limited area known as a tile. The function of these cells is to receive information from photoreceptor cells and send it along the optic nerve to the brain.

“These neurons continue to develop and elaborate their connections within their established group of cone cells in the retina,” Borghuis said. “This suggests synaptic plasticity, or the ability for the neurons to create new connections with other neurons. This is significant because in brain disease, you want to transplant and regenerate neurons and integrate them through the formation of new synapses with other neurons.”

In the first stage of the work, a team of researchers at the University of Idaho led by Peter Fuerst, Ph.D., determined that removing the gene encoding a protein known as Down syndrome cell-adhesion molecule (DSCAM) allows these cells to extend neuronal connections beyond their normal tile barriers. They genetically modified the mice to omit DSCAM from those cells, after which the cells were seen to form apparent contacts with neurons outside their tiles.

However, the researchers were unable to determine whether those apparent neural connections were, in fact, functional and capable of transmitting visual information.

That’s where Borghuis comes in. Using a unique imaging and recording technique pioneered in his laboratory at UofL, two-photon fluorescence-guided electrophysiology in deep layers of the neural retina, Borghuis recorded the bipolar cells’ responses to visual stimulation. His measurements showed enlarged visual receptive fields in the genetically manipulated retinal neurons, demonstrating that the extended cells made new, functional synapses onto cones.

“Right off the bat we could see that the receptive fields were larger, so we could tell that their visual responses were consistent with neural outgrowth and new synapse formation,” Borghuis said.

These tests proved the neural outgrowth seen by the Idaho team led to stable, functional connections with new cells.

A new joint research grant from the National Institutes of Health, awarded equally to Borghuis and Fuerst, will fund the collaborative research for another two years. During that time, they will induce the DSCAM knockout later in the lifespan to determine the identity and strength of the new synapses. In addition, they also will perform studies of neurons at later synaptic stages within the retina to determine other potential consequences of increased neuron growth at the level of the visual input.

“We have known about the tiling or mosaic structure of these cells for decades, and there are models and ideas for why neurons should tile. Now that we have a genetic tool that allows us to disrupt tiling within a neuron population experimentally, we can finally test these models,” Borghuis said.

The ability to stimulate neural outgrowth with new synaptic connections may ultimately improve humans’ ability to recover from brain and spinal cord injury or disease by supplying new neural connections. Even more promising, it could lead to neural regeneration and transplantation-based therapies for restoring visual function in retinal diseases such as diabetic retinopathy and macular degeneration.

November 8, 2017