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UofL Trager Institute works to reduce social isolation for older adults through technology innovation

Initiatives to benefit older adults during pandemic to be discussed in weekly information session Aug. 4
UofL Trager Institute works to reduce social isolation for older adults through technology innovation

Trager Institute rendering

Amid efforts to stem the spread of the COVID-19 pandemic, social isolation and loneliness have emerged as a significant public health crisis, particularly for older adults. Isolation and loneliness affect those living in facilities as well as those living on their own in the community.

In addition to the mental health implications such as depression, studies gathered by the National Institute on Aging demonstrate that prolonged social isolation can lead to other health complications, including cognitive decline, high blood pressure, heart disease and a weakened immune system. These side effects are particularly concerning during COVID-19 when such comorbid conditions put individuals at higher risk for adverse reactions from the virus. 

The University of Louisville Trager Institute is developing technologies and services to reduce social isolation while maintaining social distancing. 

“Social distancing does not have to mean social isolation,” said Anna Faul, Ph.D., executive director of the UofL Trager Institute. “We are working with community partners to bring technology and social supports to older adults facing increased social isolation due to the current pandemic.”

In April, for example, the UofL Trager Institute and Brent Wright, M.D., of the UofL School of Medicine, introduced SmartGlasses technology to long-term facilities and primary care offices. This technology allows a health care professional who is with the patient to put on the web-connected glasses and dial in with an attending physician. A camera and microphone attached to the glasses allow the physician to see and interact directly with the patient in real time.

Recent awards of nearly $190,000 from multiple organizations will allow the Trager Institute to support the expansion of additional resources, including:

  • Telehealth and teletherapy for residents in long-term care facilities
  • Training of staff and students to offer virtual interdisciplinary care coordination and chronic disease management
  • Caregiver resources such as training, support groups and counseling services focused on Jefferson County and surrounding rural counties 
  • Specialized mental health services for older adults to reduce social isolation and depression (PEARLS program)
  • A state-wide virtual-friendly visitor program that provides patients, families, caregivers and nursing home residents and staff with resources to reduce social isolation

The funding is provided by the Geriatric Workforce Enhancement Program CARES Act, the National Family Caregiver Program Title IIIE (Administration on Aging) the Health Promotion and Disease Prevention Title IIIE (Administration on Aging) as well as others throughout Kentucky. These grants have created statewide partnerships and expanded the footprint of the institute and of the university.

“Given the expansion of social isolation in our community, our team has prioritized the dissemination of technology to community-dwelling older adults,” Faul said. “In addition to the currently funded efforts, we are looking forward to the possibility of additional funds that will allow us to provide iPads and Bluetooth technology to vulnerable community-dwelling older adults in Jefferson County and several rural counties, to establish a mini-virtual health clinic network across multiple Appalachian counties and to disseminate innovative contact tracing efforts through app-based, wearable devices and AI-based services.” 

The Trager Institute hosts weekly COVID-19 information sessions that focus on the experiences of older adults, caregivers and people with chronic conditions during the pandemic. The Aug.4 information session will explore the broader efforts of our community to address social isolation through technology innovation. This session will feature Wright, associate dean for rural health innovation in the UofL School of Medicine, and Rebecca Brown Rice, director of operations at the Louisville Healthcare CEO Council. This session will explore the innovative ways technology is used to reduce social isolation and loneliness both during and after the COVID-19 pandemic. As part of this conversation, the speakers will explore the latest developments in technology, such as SmartGlasses, and creative ways to re-imagine existing technology.

The virtual session will be held Tuesday, Aug. 4, at 10 a.m., at https://zoom.us/j/884298617.

If you or someone you know is experiencing social isolation or loneliness, contact the care team at the Republic Bank Foundation Optimal Aging Clinic at the UofL Trager Institute for assistance. The care team can be reached at 502-588-4340, Option 1, Option 1, or at tragerinstitute@louisville.edu. Additional resources are available at Community Action Kentucky Partnership and Area Agencies on Aging and Independent Living, which provide social interaction programs as well as other essential services such as in-home care and food delivery programs. 

Researchers on the rise: NIH funds UofL doctoral students’ work on taste buds and brain circuitry

Researchers on the rise: NIH funds UofL doctoral students’ work on taste buds and brain circuitry

PhD student Zach Whiddon

You may be confident in your potential to pursue a career in biomedical research when the National Institutes of Health funds your work before you receive your Ph.D.

Two doctoral students in the University of Louisville Department of Anatomical Sciences and Neurobiology, Zach Whiddon and Kyle Whyland, have received funding from the NIH to support their research projects. The highly competitive F31 predoctoral training awards help set the researchers on a path to a career in research, requiring the same rigorous application process that seasoned investigators must go through to obtain NIH funding for their research.

“The receipt of an F31 award is an excellent credential and is an important part of building a career in science,” said Robin Krimm, Ph.D., a professor of anatomy and neurobiology and Whiddon’s mentor. “The award of an F31 also enable the student to be become more independent; their salary is paid from their own grant and they are responsible for reporting their research progress to the NIH.”

Whiddon, who moved to Louisville to pursue his Ph.D. after completing his master’s degree in cell and molecular biology at Eastern Michigan University, is working in Krimm’s lab to capture images of nerve cells within taste buds using a specialized technique Aaron McGee, Ph.D., another faculty member in the department, brought to UofL.

Neurons send long projections from the base of brain to the taste buds on the tongue, where terminal arbors, or branches, undergo rapid structural change. Using the technique McGee introduced, two-photon laser scanning microscopy, Whiddon developed a method to capture high resolution images of the branches as they connect to taste buds in live animal models and to document how those branches change over days and weeks.

“Taste bud cells have a very short life span, maybe 10 days. How do these neurons connect with replacement taste cells? To answer that we needed to be able to watch the neurons over time,” Whiddon said. “No one in the taste field has even attempted to look at the neurons over time. They did not think it was possible – until now.”

Already the research is showing that structural change happens much more rapidly than previously thought.

“We saw that in just a 12-hour period the arbors can add or subtract new branch ends, as much as 10 microns in length, which is very quick in terms of neural plasticity,” Whiddon said.

He plans to continue this field of research after he completes his Ph.D.

“Not a lot of people are doing this work, which is what makes it so exciting,” Whiddon said. “I think this research will be a good basis for a career – to adapt it and answer more questions. I’m interested in the plasticity aspect and what is controlling the structural rearrangements.”

Whyland’s research is focused on describing poorly understood brain circuits related to vision. The Jeffersonville, Ind., native earned a bachelor’s degree from Indiana University, majoring in psychology. Now working toward his Ph.D. with Professor Martha Bickford, Ph.D., Whyland is investigating how two specific parts of the brain, the superior colliculus and the parabigeminal nucleus, work together to process visual information and to control motor reflexes and defensive behaviors such as freezing or fleeing.

“We are trying to reverse engineer a little piece of wiring in the brain to give a model for how that might work in similar areas of the brain,” Whyland said.

Whyland’s research also takes advantage of specialized techniques being used in the labs at UofL.

“During the completion of his project, Kyle will receive training in a variety of neuroanatomical techniques, in vitro physiology and a technique called optogenetics in which specific brain cells can be activated with light pulses to interrogate brain circuit function,” Bickford said.

Both Whyland and Whiddon are grateful for the funding provided by the NIH – about $32,000 per year each – as well as the opportunity to learn the ropes of funding applications.

“If Kyle and Zach continue as research-active faculty members, they will be applying for grants throughout their careers,” Bickford said. “The F31 application gives students their first in-depth exposure to the NIH application process, including stringent reviews by a panel of experts.”

As with any competitive process, success is validating. For Whyland, however, the opportunity to revise and resubmit a project that initially was rejected was one of the most rewarding aspects of the experience.

“The first time I submitted it, it wasn’t even scored. By addressing the NIH reviewers’ specific concerns, I was able to resubmit it and get it funded,” Whyland said. “It was very satisfying to know that if you don’t get discouraged and try to address the criticisms, you can be rewarded. It was really motivating.”

 PhD student Kyle WhylandPhD student Kyle Whyland

Mengwei Jiang, PhD candidate in pharmacology and toxicology awarded NIH Ruth L. Kirschstein Predoctoral National Research Service Award

Mengwei Jiang, a pharmacology and toxicology program PhD candidate in the laboratory of Dr. Wenke Feng, has been awarded a Ruth L. Kirschstein Predoctoral Individual National Research Service Award (F31) from the NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM for his PhD research entitled “Probiotic and intestinal miR194 regulation of bile acid metabolism in alcoholic liver disease”. This three year fellowship will support Mengwei’s research in the field of alcoholic liver disease.

Mengwei matriculated into the PhD program in pharmacology & toxicology via the PhD partnership program with Jilin University.

 

Incoming Students of 2020 to go through e-orientation

On Monday August 10 the Department of Microbiology & Immunology will host a virtual orientation for our Fall 2020 incoming students.  Faculty who are accepting new students into their laboratories will e-present their programs.  Welcome Taylor Garrison, Michelle Hallenbeck, Katelyn Sheneman, Peter Shin, Shikha Srivastava and Cassie Woolley!

Phase II results of Co-Immunity Project show higher-than-expected rates of exposure to novel coronavirus in Jefferson County

Study finds 4-6 times higher rates of exposure to the virus than previously detected
Phase II results of Co-Immunity Project show higher-than-expected rates of exposure to novel coronavirus in Jefferson County

Prevalence of COVID-19 in Jefferson County in June 2020

Results from the second phase of the University of Louisville’s groundbreaking project to track COVID-19 in Jefferson County show that 4 to 6 times more people than previously reported may have been exposed to the virus since the beginning of the pandemic.

From June 10-19, researchers conducting Phase II of the Co-Immunity Project tested members of the Louisville community for both the presence of the novel coronavirus in the participant’s nasal passages and for antibodies against the virus in their blood. Samples were collected at five community drive-up locations across Louisville by UofL Health and researchers from the University of Louisville’s Christina Lee Brown Envirome Institute. Samples were analyzed by UofL’s Center for Predictive Medicine for Biodefense and Emerging Infectious Disease (CPM) in its Regional Biocontainment Laboratory (RBL).

To obtain a representative sample for the study, households in Jefferson County were organized into geographic regions based on U.S. Census Bureau tract boundaries. Households within each region were sent invitations to participate in proportion to the population of that region. Within the regions, areas that had higher concentrations of non-White residents were sampled at a higher rate to increase their representation.

Invitations were mailed to a total of 18,232 addresses. Based on the ages and sexes of all adults in the household as provided by those responding to the invitation, one adult from each household was asked to provide a sample.

The researchers tested 509 people who responded to the mailed invitations. An additional 1,728 community members booked appointments on their own and were tested after hearing about the study in the news or on social media. Many individuals who were invited to participate did not book an appointment. 

Of the 2,237 individuals who were tested, 10 percent were non-White. The ages of tested individuals was as follows:

  • 21 percent between 18-34
  • 40 percent between 35-59
  • 40 percent age 60 or older

Residential locations of the 2,237 participants are shown in Map 1.  Overall, nearly 0.4 percent of the population of Jefferson County was sampled.

Analysis of the study data found that at least 0.05 percent of the participants had an active infection during the time of the study and approximately 4 percent (5.1 to 3.2 percent) of people had detectable levels of antibodies in their blood, indicating they had been exposed to the virus earlier in the year.

“These results allow us, for the first time, to more accurately estimate the spread of coronavirus within our community. If we extrapolate the results from this study to the general population, it would suggest that as many as 20,000 people may have been exposed to the virus – many more than the 3,813 cases reported in the city by the end of June,” said Aruni Bhatnagar, Ph.D., director of the Brown Envirome Institute.

This difference may be due to the fact that people did not have symptoms and were not aware they were infected.

“We were told by several participants that they believed they had COVID-19 before testing was widely available. Nonetheless, our preliminary data suggest that the estimated number of people who have had COVID-19 may be 4-6 times higher than those who have tested positive to-date,” said Rachel Keith, Ph.D., assistant professor of environmental medicine at UofL who conducted the study. “This suggests that the virus is much more widespread in our community than previously estimated. I believe this indicates a need for continued and widespread testing, including antibody testing, which plays an important role in understanding the spread of disease.”

“The random sampling of the population also allows us to calculate the true mortality associated with COVID-19,” Bhatnagar said. “Previous estimates of COVID-19-related mortality have varied from 0.5 to 15 percent. However, given that the city had reported 209 deaths by the end of June, our results suggest that the rate of mortality associated with the virus, at least in Kentucky, may be 1.3 percent. This is significantly higher than the 0.65 percent rate suggested by the CDC. Our research suggests that many who are infected with the virus nationwide have not been tested and that there is urgent need to continue random testing so that we can calculate the most accurate mortality rate,” Bhatnagar said.

The study data also provide an estimate of the spread of the infection in Louisville.

“Because participants were drawn from all parts of the city, we could estimate which areas have had the highest rates of infection,” Keith said. “Although we are still analyzing all our data, our early results show that the highest cluster of individuals exposed to the virus is in Western Louisville. (See Map 2).  We found that the prevalence of exposure was twice as high in non-White participants as in White participants. Most (54 percent) of those who tested positive for the antibody were between the ages of 35-59 years old,” she said.

The researchers cautioned that because so little is known about SARS-CoV-2 and because the rates of community infection and exposure are changing rapidly, the results of this survey are applicable only to the period of June 10-19.

“Although many individuals had detectable levels, the amount of antibodies in blood varied greatly among the participants,” said Kenneth Palmer, Ph.D., director of the CPM. “As a result, we are not sure to what extent they are protected from re-infection. Indeed, some of our early results show that the levels of antibodies decline rapidly within a month. Therefore, we are planning to re-measure individuals who had antibodies in their blood to see if those levels are maintained over time and if so, for how long.”

Currently, the researchers are repeating the antibody test in those health care workers who were found to have anti-SARS-CoV-2 antibodies during Phase I of the Co-Immunity Project. They also plan to repeat community-wide testing in Jefferson County in September.

This study was supported in part by the James Graham Brown Foundation. The Co-Immunity Project is a collaboration of the UofL Christina Lee Brown Envirome Institute, the Louisville Healthcare CEO Council and three health systems in Louisville – Baptist Health, Norton Healthcare and UofL Health.

UofL technology that may inhibit pathway for cancer gets commercial partner

Researchers say the technology could solve “one of the holy grails” of cancer treatment
UofL technology that may inhibit pathway for cancer gets commercial partner

Geoffrey Clark, Ph.D.

A University of Louisville-born invention that may help treat cancer now has a commercial partner.

Qualigen Therapeutics Inc., a California biotechnology company focused on developing novel therapeutics for the treatment of cancer and infectious diseases, has signed a license agreement for the technology and plans to fund continued development with UofL to ready it for market.

The technology works by targeting the RAS protein, which sends signals that regulate when and where the body produces and grows new cells. When mutated, the protein turns into a “stuck accelerator pedal,” according to UofL researcher Geoffrey Clark, Ph.D., who co-invented the technology with colleagues John Trent, Ph.D., and Joe Burlison, Ph.D.

“Normally, it gets pressed when you need to grow and then the foot comes off and the cell slows down,” said Clark, professor of pharmacology and toxicology at UofL. “When it becomes mutated, the accelerator’s jammed on, with cells continuing to grow and ultimately becoming a cancerous tumor.”

The drug targets only the active RAS protein and, so far, has little toxic effect on healthy cells. Many current non-targeted treatments, such as chemotherapy, can hurt both healthy and cancerous cells, leading to painful side effects. By some estimates, targeting this mutation could stop the growth of at least a third of human tumors.

“The patient impact could be extremely broad because RAS is involved in a lot of different cancers,” Trent said. “It’s one of the holy grails that there has been limited success in targeting.”

Trent leads the Molecular Modeling Facility (MMF) at UofL Health – James Graham Brown Cancer Center and the UofL partnership with Dataseam, a non-profit with a network of school computers across the state. When the computers aren’t being used by students, they’re connected to act as a distributed supercomputer, allowing researchers to process and analyze huge amounts of data.

Trent used that capability to run through millions of cancer-fighting drug possibilities in a matter of days. The result was a drug that could inhibit the deregulated RAS protein. Development of the technology was supported by the UofL NIH REACH ExCITE program.

Qualigen holds an exclusive license to the technology through the UofL Commercialization EPI-Center, which works with startups and industry to commercialize university-owned technologies. This license agreement builds on a sponsored research agreement with Qualigen for the development of several small-molecule RAS Inhibitor drug candidates. Qualigen also has licensed and is developing other UofL technologies for fighting COVID-19 and cancer.

“Partnering on this new cancer-fighting technology is another example of the relationship we’ve developed with the University of Louisville,” said Michael Poirier, CEO of Qualigen. “We look forward to working with UofL and to advancing this important clinical program with the goal of developing an effective treatment for this unmet need."

If you are interested in supporting this cancer research at UofL, visit give.louisville.edu/JGBCC-Enhancement or contact Elea Fox at elea.fox@louisville.edu.

UofL conducting clinical trial on drug for severe COVID-19 respiratory effects

UofL conducting clinical trial on drug for severe COVID-19 respiratory effects

A clinical trial for Aviptadil (RLF-100) is underway at UofL for severe COVID-19 patients. Image courtesy NeuroRx and Relief Therapeutics.

The University of Louisville is conducting a clinical trial on a new treatment for critically ill COVID-19 patients meant to lessen some of the most severe and deadly respiratory effects.

The treatment, a new formulation of Aviptadil (RLF-100), produced by Pennsylvania-based NeuroRx and Relief Therapeutics Holding, SA, of Geneva, works by combating “cytokine storm,” an unchecked overreaction of the body’s immune response. These storms can cause severe lung inflammation and stiffening that make it difficult, if not impossible, for patients to breathe on their own.

“We want to mitigate these storms,” said the clinical trial lead, Rainer Lenhardt, M.D., associate professor of anesthesiology and critical care in the UofL School of Medicine. “We’re doing anything we can to improve outcomes.”

COVID-19 is primarily a respiratory disease and about 80 percent of cases are mild to moderate, according to WebMD. But in severe and critical cases, the lungs can swell and fill with fluid as the body tries to fight off the infection. This severe respiratory failure is a major cause of COVID-19-related death.

“These patients are terribly ill,” said Forest W. Arnold, D.O., M.Sc., an investigator on the clinical trial and an associate professor in the UofL Division of Infectious Diseases. “And because this virus is so novel, options for treatment are just now being developed. This gives us another option.”

In this Phase 2b/3 trial, UofL and other sites will treat at least 144 patients. To be eligible, participants must be patients at UofL Hospital receiving intubation and mechanical ventilation due to COVID-19-induced severe respiratory failure. Phase 2 and Phase 3 trials determine effectiveness and monitor for adverse reactions. A list of other ongoing clinical trials at UofL is available here.

The drug has previously been used for other indications, but in this formulation, it acts as an anti-inflammatory agent. The formulation is believed to protect alveolar type-2 cells in the lungs which are essential to oxygen exchange and are thought to be a major target of the SARS-CoV-2 virus.

In Phase 1 trials, designed to assess safety and dosage, seven of eight patients with acute respiratory distress caused by sepsis were taken off breathing machines after receiving the drug and six eventually left the hospital.

“Our No. 1 goal is to provide a potentially life-saving therapy to critically ill patients with COVID-19. The FDA has granted fast-track designation for RLF-100 underscoring the urgent need for new treatment options,” said Jonathan Javitt, M.D., M.P.H., CEO and chairman of NeuroRx. “We are excited to work with UofL and leverage its clinical research and infectious disease expertise to advance research in COVID-19.”

Since the coronavirus pandemic began, UofL has taken a leadership role in investigating and developing innovative ways to prevent, diagnose and treat the virus. Researchers are working to block coronavirus from infecting human cells, launching groundbreaking initiatives for testing, building robots that can sanitize high-risk areas and more. If you are interested in supporting this or other COVID-19 research at UofL, contact Lisa Warner at lisa.warner@louisville.edu or visit give.louisville.edu

 

Longtime faculty member and clinician Soltau named permanent chair of ophthalmology and visual sciences

Longtime faculty member and clinician Soltau named permanent chair of ophthalmology and visual sciences

Joern B. Soltau, M.D.

Joern B. Soltau, M.D., has been named the Dr. William H. and Mrs. Blondina F. Evans Endowed Chair of the Department of Ophthalmology and Visual Sciences in the University of Louisville School of Medicine.

Soltau served as acting chair of the department since November 2018 and has been a member of the UofL faculty since 1998. In clinical practice, Soltau is a glaucoma specialist with UofL Physicians – Eye Specialists. He is board certified by the American Board of Ophthalmology.

Soltau was born in Hong Kong and grew up in Germany. He earned his M.D. from Ruprecht-Karls Universität in Heidelberg, Germany, in 1988, followed by an internship in ophthalmology at Klinikum Mannheim in Germany. After spending two years in research at UofL in the Kentucky Lions Eye Center, he completed his residency at Washington University School of Medicine in St. Louis, followed by a year as chief resident at the same institution. He then completed a glaucoma fellowship at the Bascom Palmer Eye Institute in Miami.

At UofL, Soltau served as residency program director from 2001-2016. He received the American Academy of Ophthalmology Achievement Award in 2018 and was listed among Louisville’s Top Surgeons in Louisville Magazine for Cataract Surgery in 2010 and 2018.

“I am confident Dr. Soltau will continue to be a good fit for leading the department into the future, building on its strong tradition of research, clinical care and education,” said Toni Ganzel, M.D., M.B.A., dean of the School of Medicine.

Soltau’s appointment as chair of the department was effective April 1.

UofL announces new Department of Radiology chair

UofL announces new Department of Radiology chair

Sohail Contractor, M.B.B.S.

The University of Louisville has named Sohail Contractor, M.B.B.S., the J.T. Ling M.D. Endowed Chair of Radiology in the UofL School of Medicine.

Prior to joining UofL, Contractor was a professor of Radiology at Rutgers New Jersey Medical School.

In addition to his role as chair of the Department of Radiology in the School of Medicine, Contractor is a radiologist at UofL Health – UofL Hospital. He is board certified by the American Board of Radiology and the American Board of Internal Medicine. His clinical and research focus is on hepato-biliary and transplant interventions.

Contractor is a 1992 graduate of Grant Medical College in Bombay, India. He completed residencies in internal medicine at Coney Island Hospital in Brooklyn, N.Y., and diagnostic radiology at the University of Medicine and Dentistry of New Jersey, Newark. He completed a fellowship in vascular and interventional radiology at New York University Medical Center in New York. Contractor is a founding member of the Society of Interventional Oncology and a Fellow of the Society of Interventional Radiology.

Contractor was named among “New Jersey Top Doctors, The Very Best Physicians, Experts in Their Field” and received the “Golden Apple Award” as a subspecialty teacher at Rutgers New Jersey Medical School in 2015. He received a Certificate of Leadership Mastery at the Radiology Leadership Institute, American College of Radiology, in 2016 and completed MBA Essentials at the London School of Economics in 2018.

“Dr. Contractor’s talent, skills and energy will be a good fit for leading the department into the future,” said Toni Ganzel, M.D., M.B.A., dean of the School of Medicine. “I know he will build on the department’s many strengths and will seek new opportunities in this changing clinical environment.”

Contractor’s appointment as chair of the Department of Radiology was effective June 1.

Psychiatry professor elected to American Telemedicine Association College of Fellows

Psychiatry professor elected to American Telemedicine Association College of Fellows

Robert Caudill, M.D., DFAPA, FATA

The global pandemic has brought significant changes to most industries, including health care. Adoption of telemedicine is on the increase, an achievement recognized by one of the newest inductees to the American Telemedicine Association (ATA) College of Fellows – Robert Caudill, M.D., DFAPA, FATA.

Caudill is professor and director of Telemedicine and Information Technology programs in UofL’s Department of Psychiatry and Behavioral Sciences, and will be recognized as part of the Class of 2020 Fellows during the ATA virtual conference on June 25.

“It is so important for individuals to have access to mental health care especially during this arduous time, and it is encouraging to see both practitioners and patients utilizing the technology that allows for remote access to services,” Caudill said.

The ATA College of Fellows recognizes individuals and organizations for significant achievements in telehealth, service to the general telehealth community and service to the ATA.

Caudill is past chair for the ATA’s Telemental Health Special Interest Group and co-chair of the Telehealth Interest Group of the National Network of Depression Centers. He serves as a founding member of the American Psychiatric Association’s committee on telepsychiatry.

He also is the residency training director in the Department of Psychiatry, and has an interest in optimizing the role of technology in post-graduate medical education and psychiatric patient care. He lectures on topics related to technology, community psychiatry and psychopharmacology. Along with his faculty appointment, Caudill serves as a staff psychiatrist with several community mental health agencies in Kentucky.

UofL immunologist discovers biomarker warning of cellular crisis that could cause death in COVID-19 patients

Research may pinpoint way to save lives of approximately 20 percent of all COVID patients
UofL immunologist discovers biomarker warning of cellular crisis that could cause death in COVID-19 patients

Diagram showing levels of neutrophil immune cells (red dots) in a healthy donor, a patient with moderate COVID-19 and a patient with severe COVID-19

Jun Yan, M.D., Ph.D., professor of surgery and microbiology and immunology at the University of Louisville, led a team of researchers in the discovery of an important biomarker that predicts a crisis in COVID-19 patients that could lead to death.

Yan, an immunologist and researcher with the UofL Health - James Graham Brown Cancer Center, along with UofL Professor of Anesthesiology Jiapeng Huang, M.D., Ph.D., and M.D./Ph.D. student Samantha Morrissey, Ph.D., conducted a patient study to better understand the most severe cases of COVID-19.

Approximately 20 percent of COVID-19 patients experience severe disease, including pneumonia and acute respiratory distress syndrome (ARDS). In some of these patients, the rapid influx of immune cells to the lungs to fight the infection leads to complications in the lung and blood coagulation disorders, resulting in heart attack, pulmonary embolism, stroke or deep vein thrombosis.

To better understand these serious complications, Yan’s team evaluated levels of various immune cells in blood samples of COVID-19 patients and compared those levels with those of healthy individuals. They discovered that one type of immune cells, low-density inflammatory neutrophils, became highly elevated in some patients whose condition became very severe. This elevation signaled a point of clinical crisis and increased likelihood of death within a few days.

Neutrophils are one type of immune cells that serve as the first line of defense in the body. When an individual acquires an infection, neutrophils rush to the site to clear the pathogen causing the infection. However, if their presence is persistent or there is a very high volume of cells at the site of infection, in this case the lungs, they can cause unwanted adverse effects. In the case of patients with severe COVID-19, a blood clotting disorder known as coagulopathy occurred, that can manifest as pulmonary embolism, heart attack or stroke.

The study, published online as a preprint, details shifting levels of these neutrophils and other immune cells through repeated blood samples from study participants, correlated with improvement or worsening of the patients’ condition. If clinicians could detect a rise in these cells, they may be able to provide therapy to prevent the potential life-threatening conditions associated with them.

“Based on this study, we believe that the low-density inflammatory band neutrophil population contributes to COVID-19-associated coagulopathy (CAC) and could be used as a clinical marker to monitor disease status and progression,” Yan said. “Identifying patients who are trending toward a cellular crisis and then implementing early, appropriate treatment could improve mortality rates for severe COVID-19 patients.”

To provide additional clinical options for physicians in addressing these crises, Yan is now working with other researchers at UofL to test potential therapies.

Data analysis by Corey T. Watson, Ph.D., David Tieri, Ph.D., and M.D./Ph.D. student Anne Geller.

 

June 17, 2020

Groundbreaking COVID-19 antibody initiative receives $1.5 million to expand testing, launch “virus radar”

Gift from James Graham Brown Foundation will aid in safer re-opening of Kentucky

The Co-Immunity Project, a groundbreaking collaboration to track and curb COVID-19 in Kentucky, has received $1.5 million from the James Graham Brown Foundation, as well as additional gifts, to expand community coronavirus testing and launch a public ”virus radar” for understanding its spread.

“We are deeply grateful for this timely philanthropic support that enables us to begin the next phase of the Co-Immunity Project," said Neeli Bendapudi, president of the University of Louisville. “It is vital for decision makers to have the information to track virus activity as the economy continues phased reopening. Knowing where the virus is will help us avoid a second wave.”

The new investment will support unique, three-step testing of individuals in the community for COVID-19 and SARS-CoV-2 antibodies along with testing of wastewater. The goal is to develop a real-time picture of the virus, beginning in Jefferson County, with the hope of later spreading this model to other affected communities worldwide.

“The James Graham Brown Foundation is pleased to join the efforts of the University of Louisville and other funders in this crucial work that will benefit and inform how we manage the COVID-19 pandemic,” said Mason Rummel, president and CEO of the James Graham Brown Foundation (JGBF). “The University of Louisville and the Co-Immunity Project team’s swift action and proactive approach will help our community mitigate the impact of this virus now and in the future.”

A previously announced substantial gift from the Jewish Heritage Fund for Excellence and other individual donations enabled the completion of Phase I of the research, which included the testing of more than 1,000 health care workers in all three area hospital systems: Baptist Health, Norton Healthcare and UofL Health. The results of this work will be shared very soon.

The JGBF gift will help the project launch its Phase II, in which some 22,000 community members will be tested for the virus and associated antibodies.

Households will receive invitations in the mail to participate in this research from the University of Louisville. From those who sign up in response to the mailing, individuals will be selected to participate in testing based on age, race, sex, background and location to create a sample that matches the demographics of the overall population of Jefferson County.

A new group of participants will be selected every six weeks for virus testing and antibody testing. If someone receives the mailing and signs up on the Co-Immunity Project website, they may be called right away, they may be called for a later group or they may not be called.

Participants in this project will receive more than COVID-19 diagnostic tests. They also will be tested using cutting-edge antibody testing available at UofL to determine how much immunity was generated by such exposure and to identify those with the best immune responses as donors of high-quality plasma for treating patients with advanced COVID-19. This antibody testing is more accurate, specific and reliable than most antibody tests, providing much more significant data.

The three-step antibody testing to understand and make use of patient immunity is conducted at the UofL Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases (CPM), which has established a high-throughput, real-time assay for antibodies from SARS-CoV-2, the coronavirus variant that causes COVID-19.

This comprehensive testing program identifies people with antibodies, their levels and quality, and tracks the evolution of the participants’ immunity. The CPM will utilize its NIH-designated Regional Biocontainment Laboratory, one of just 12 such facilities in the United States and the only one in Kentucky, to test for the neutralizing activity of the antibodies.

“It is very important that the citizens of Jefferson County respond to this call for particpants,” said Aruni Bhatnagar, Ph.D., director of the Envirome Institute. “We cannot do this research without the participation of residents from every part of the metro area.”

Scientists from across the globe will have access to the resulting anonymized data for future study on the effectiveness of antibody therapy. The data also may be used to better identify individuals who are better able to fight off the coronavirus.

The Co-Immunity Project is a collaboration of the University of Louisville Christina Lee Brown Envirome Institute and the Louisville Healthcare CEO Council, along with Louisville’s three major health systems, Baptist Health, Norton Healthcare and UofL Health.

 

Follow this link for a video of the news conference announcing Phase II and the James Graham Brown Foundation gift. 

Multi-partner programs serving moms in recovery focus of new UofL study

Robert Wood Johnson Foundation's Aligning Systems for Health grant to support the work
Multi-partner programs serving moms in recovery focus of new UofL study

Freedom House bedroom located in Manchester, Ky.

A University of Louisville study will evaluate how health care, public health and social services organizations are working together to improve the health and well-being of individuals served through Freedom House programs in Louisville and Manchester, Ky.

Freedom House, operated by Volunteers of America Mid-States (VOAMID), is a residential treatment program for alcohol and/or drug dependent pregnant women and women with young children.

The research will examine Freedom House and its recent expansion into eastern Kentucky, determining how well and in what ways the urban and rural partners align in terms of purpose, data sharing, financing and governance.

Aligning Systems for Health Program, led by the Georgia Health Policy Center and supported by the Robert Wood Johnson Foundation, has awarded UofL more than $290,000 to fund the two-year study. UofL is one of seven institutions to receive the competitive funding. 

UofL researchers Liza M. Creel, Ph.D., MPH, assistant professor, School of Public Health and Information Sciences, and co-director, Commonwealth Institute of Kentucky, and Deborah Winders Davis, Ph.D., director, Child and Adolescent Health Research Design and Support Unit, Division of Clinical and Translational Research in the Department of Pediatrics, will lead the study. 

“We’ll focus on health equity and investigate similarities and differences between settings as it relates to program implementation and success of clients in the Freedom House program. We look forward to sharing data-driven insights around how organizations across sectors can work together to improve outcomes for the people and the communities they serve,” Creel said. 

“We are so pleased to collaborate with UofL on this study that will ultimately help pregnant and parenting moms in our Freedom House programs have even better recovery outcomes in both our urban and rural communities,” said Jennifer Hancock, president and chief executive officer of Volunteers of America Mid-States. 

VOAMID operates three evidence-based residential, licensed clinical treatment programs in Louisville. The Freedom House programs treat mothers’ substance use disorder, promote the birth of healthy babies, reunite families and reinforce positive behavior changes. Annually, the Louisville programs serve approximately 170 women, and more than 200 babies and children. 

Earlier this year, the organization expanded into eastern Kentucky with a new site in Clay County, a rural area hit hard by opioid use, with high rates of Neonatal Abstinence Syndrome and out-of-home foster care placements much higher than Kentucky’s overall rate (91 vs. 43 per 1,000 children). This location can serve more than 60 women, 30 newborns, and 50 minor children each year.

Managing Polypharmacy in the 15-Minute Office Visit

Polypharmacy is an underappreciated factor in undesirable patient outcomes. In older adults, polypharmacy is considered a syndrome of harm and presents a challenge to primary care providers. The United States has one of the highest medication use rates per capita in the world.
https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0095454317300532?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0095454317300532%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.ncbi.nlm.nih.gov%2F

A Review on Strategies to Manage Physician Burnout

Physician burnout is an emerging condition that can adversely affect the performance of modern-day medicine. Chronic overwork, constant stressors, and a poor work environment cause emotional exhaustion, depersonalization, and a reduced sense of personal achievement.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682395/

COVID-19 Clinician Resources

 A searchable database of accredited continuing education (CE) activities and additional resources that can help the CE provider and clinician community respond to the novel coronavirus (COVID-19) public health emergency.
https://accme.org/resources-category/novel-coronavirus-education

Delivering health care through a new lens: smart glasses

Delivering health care through a new lens: smart glasses

R. Brent Wright, M.D., wearing the smart glasses

The COVID-19 pandemic has led to the expansion of telemedicine, and as part of that expansion, faculty at the University of Louisville are piloting new smart glasses for advanced delivery of health care.

“There is both an urgent and widespread need to not only treat patients but deliver expertise and training remotely and safely to both professionals and medical learners,” said R. Brent Wright, M.D., associate dean for rural health innovation at the UofL School of Medicine, who has been working with various companies to explore a smart glasses solution for telemedicine since 2014.

Long-term care (LTC) facilities and emergency departments represent two of the areas with greatest need for the glasses for direct physician care during the pandemic. The UofL Trager Institute, emergency medicine and psychiatry are part of a feasibility study to test the Vuzix M400 smart glasses.

“It is imperative that we find solutions for health care to continue for the vulnerable nursing home population in Kentucky,” said Anna Faul, Ph.D., executive director and professor, UofL Trager Institute. “The use of smart glasses to provide real-time, expert geriatric care to residents of long-term care facilities is a huge step in increasing access to care, particularly during COVID-19. Each nursing home in our study will receive smart glasses that will allow for remote video consults with specialized medical providers and behavioral health experts without the need for the providers to enter the facilities and expose themselves and other patients to COVID-19.”

The concept is fairly straightforward. An advanced practice nurse practitioner or other health care professional working at a LTC facility will put on the web-connected glasses and dial-in with an attending physician through the Zoom conference platform. A camera and microphone are attached to the glasses, and the technology has the potential to display and obtain information for the physician to access remotely. The physician can see and interact directly with the LTC resident, providing immediate consultation and evaluation.

The glasses allow for ease of mobility and hands-free interaction for the on-site provider, an advantage over current standard telehealth delivery which requires computers and monitors to be transported from bed-to-bed on large carts. Additionally, data can be input into medical records hands-free, and can be controlled by voice-commands.

Smart glasses will support health care workers at five LTC facilities and one emergency department in Kentucky. UofL researchers will conduct a brief feasibility study related to the use of these six pairs of smart glasses. If the data is promising, the study will be extended. Once the pandemic has subsided, researchers hope to investigate the utility of usage for medical education.

“This technology holds great promise. UofL faculty are exploring how to transform health care and this is part of an innovative solution as we provide care and educate the next generation of physicians,” said Toni Ganzel, M.D., dean of the UofL School of Medicine, and vice president for academic medical affairs.

“The pandemic has served as the catalyst for changing delivery of care. When you have to do things so rapidly and emergently there is a call to be creative and innovative. Telemedicine allows us to share expertise while keeping a safe distance, and the smart glasses are very high-fidelity.

“The timing had to be right for this technology to become more accepted. It will be big part of health care moving forward, even after this swell with the COVID-19 pandemic, and it will be exciting to see some of our current medical residents incorporate telemedicine into their future practices,” Wright said.

Bizarre 66 million-year-old fossil from Madagascar provides clues on early mammals

UofL professor helps identify Adalatherium as part of enigmatic Southern Hemisphere mammalian group that lived at the time of dinosaurs
Bizarre 66 million-year-old fossil from Madagascar provides clues on early mammals

Lifelike rendering of Adalatherium. Image courtesy Denver Museum of Nature & Science/Andrey Atuchin

Several years ago, Guillermo Rougier, Ph.D., professor in the Department of Anatomical Sciences and Neurobiology at the University of Louisville, was approached by David Krause, Ph.D., curator at the Denver Museum of Nature & Science, to help identify a complete, 3-D fossil he had discovered on Madagascar.

“When Dr. Krause showed it to me in a scientific meeting and asked me for my opinion, I said I had never seen anything like this,” Rougier recalled. “This mammal has teeth for which we have no parallel.”

Krause and a team of paleontologists discovered the fossil during an expedition in Madagascar and spent more than a decade working to determine where it falls in the long history of mammalian evolution and what it tells us about geography and changes in global fauna over time.

Rougier, a paleontologist who specializes in the study of the skull and teeth of ancient mammals, was intrigued and joined the international team of researchers to thoroughly analyze the fossil. Their analysis was published today in the journal Nature.

The fossil is remarkably complete, an extremely rare find for ancient mammals that lived alongside the dinosaurs. Rougier described the creature as very roughly resembling a beaver or a small capybara.

“First, it is surprising how complete it is,” Rougier said. “Second, this fossil is preserved in three dimensions. When you have an animal that dies and is preserved in the rocks, the weight of the rocks on top of it flattens it out. Often it looks like a steam roller ran over it. So you might have a complete skeleton but it will be the thickness of a piece of paper – all splat out. This animal was preserved in 3-D so this gives us a wealth of detail that we very rarely have in other specimens.”

The research team named the creature Adalatherium, which is translated from the Malagasy and Greek languages and means “crazy beast,” a nod to its bizarre characteristics. They placed it among gondwanatherians, a poorly known group of mammals found in various locations in the Southern Hemisphere. Rougier used the teeth and skull of the animal to figure out how to relate it to other mammals that were living at the time and afterward.

“Teeth in mammals reflect their ancestry, diet and environment. In the case of Adalatherium, the morphology is so peculiar that it is hard to use the characters we normally use to establish family relationships,” Rougier said. “Mammalian systematics and evolution rest heavily on dental morphology, so when you do not have teeth – or they are so strange that you do not know what to do with them (think of anteaters, whales, armadillos and pangolins) – we have a problem.”

Rougier was part of the expeditions in which the first gondwanatherians were discovered in his native Argentina in the 1980s, but relatively few specimens of the group have been found since then. That makes this unusually complete discovery in Madgascar exceptionally useful in forming a more accurate picture of the enigmatic group.

Madagascar, an island off the coast of Africa, is known for unique animal species that developed in isolation over millions of years. The island broke off from India and over a period of 100 million years moved toward Africa, yet never quite arrived, allowing the animals to evolve distinctly from the larger continents.

Adalatherium is a product of this time of isolation when Madagascar was an island, detached from India and shifting towards Africa, but before there was any African influence. So it was basically an experiment, an example of what we call island biogeography or island evolution,” Rougier explained.

“Long isolated places produce very unique results in biology,” Rougier said. “These fossils keep reminding us of the unexpected forms and shapes that evolution can take over long periods of time in an isolated place. Adalatherium is an animal for which we don’t have any real parallels.”

Although the discovery of Adalatherium is a breakthrough in understanding the gondwanatherians, there still is a great deal the scientists do not know about the animals of this time and place.

Adalatherium is just one piece, but an important piece, in a very large puzzle on early mammalian evolution in the Southern Hemisphere,” Krause said. “Unfortunately, most of the pieces are still missing.” 

PhTx PhD student Sophie Sears awarded individual NIH F31 predoctoral fellowship

 Sophie Sears, a pharmacology and toxicology program PhD candidate in the laboratory of Dr. Leah Siskind has been awarded an individual NIH F31 predoctoral fellowship from the NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES.  Her dissertation project is "Role of macrophages in cisplatin-induced kidney injury and progression to chronic kidney disease"

Decontamination program begins at UofL to alleviate mask shortage for area health care workers

No-charge program allows up to 20 uses of scarce N95 respirators for health care and community organizations
Decontamination program begins at UofL to alleviate mask shortage for area health care workers

Vaporized hydrogen peroxide (VHP) generator and room prepared for N95 respirator decontamination

Health care workers and first responders put their own health at risk every time they come face-to-face with someone who has – or may have – COVID-19. Often, the only thing between these workers and the virus is an N95 respirator. But a critical short supply of the masks could leave front-line workers unprotected, placing them, their families and other patients at risk of transmitting the virus.

The University of Louisville is offering a program to decontaminate used N95 respirators, boosting the supply of masks for local health care providers, first responders and community organizations such as nursing homes at no charge.

The N95 Decontamination Program, announced April 11 by Louisville Mayor Greg Fischer, will begin next  week, sterilizing up to 7,000 N95 masks per day using vaporized hydrogen peroxide (VHP). This process has been validated by Battelle Memorial Institute as a way to allow the masks to be reused safely by health care workers.

The respirators, which protect health care workers from up to 95 percent of small particles, including viruses, normally are discarded after a single use. However, the critical shortage of N95 masks amid the global COVID-19 pandemic has forced some health care workers to use masks longer than recommended or use other, less effective masks. Given the shortage, the CDC is not objecting to reuse of masks that have been decontaminated under the emergency circumstances, using processes that have been proven to be effective.

In her efforts to ensure a supply of personal protective equipment for the university, Cheri Hildreth, M.B.A., director of the UofL Department of Environmental Health and Safety, was investigating reports on various decontamination processes for N95 respirators. She heard about other institutions that were using VHP successfully.

“Clearly, VHP was looking like the real deal. I checked with Leslie Sherwood, as I thought she had a VHP generator for the university’s gnotobiotic laboratory,” Hildreth said. “When I started seeing the data on VHP, I said we need to activate on this.”

Leslie Sherwood, D.V.M., assistant vice president for research services and director of Research Resources Facilities at UofL, confirmed they did have the device, one of fewer than 100 in use across the country. The device vaporizes hydrogen peroxide that destroys bacteria and viruses in the air and on surfaces, and is used to decontaminate the contents of an entire room.

“We use the Bioquell VHP generator to disinfect rooms in the vivarium to keep our facilities and equipment very clean for our animals,” said Sherwood, who has orchestrated the decontamination project. “We also have used it for other decontamination needs that pop up. This has popped up.”

Sherwood and Hildreth assembled a team and set the project in motion in a matter of just a few days. They modeled the UofL decontamination process on one developed by Battelle using a Bioquell VHP generator following the 2014 Ebola outbreak and took cues from colleagues who developed a similar program at Duke University. Bioquell and Duke both have applied for Emergency Use Authorizations (EUA) from the U.S. Food and Drug Administration for the process. Battelle already has received an EUA from the FDA for the process.

So far, more than 30 organizations and facilities in Louisville, southern Indiana, Lexington and northern Kentucky have expressed interest in participating or applied on the project’s website.

“The ability to extend the life of our PPE eases the strain on access to a limited supply worldwide,” said Bob Van Burskirk, director of supply chain at UofL Health. “While our days-on-hand stock of PPE remains adequate, the safe reuse of select items ensures another level of safety for our front-line physicians and nurses.”

Participating facilities will be provided site-specific, dedicated collection containers for the used N95 respirators. Once filled, the containers are sealed, decontaminated, picked up by UofL staff members and brought to the Kosair Charities Clinical and Translational Research building on UofL’s Health Sciences Center campus. There, they are placed in a negative pressure air flow room in the lab with wire shelving strung with paper clips, each room holding 3,500 – 4,000 masks. The negative pressure air flow ensures that any air in the room is filtered and exhausted out of the building, not back into the hallway.

The used masks are hung and laid on wire shelves, arranged so that every surface is fully exposed to air, and the entire room is treated with VHP for 1-2 hours. The VHP is then allowed to dissipate, which takes another 4-5 hours.

After treatment with VHP, the masks are inspected for damage, staining or deformities, given a tally mark on the strap to indicate they have been decontaminated, and boxed to be returned to the same facility from which they were collected. Once the masks have 20 tally marks, they are discarded.

“When they are clean, we go through the quality assurance checks to make sure the elastic is not broken and there is no wear and tear,” said Steven Davison, D.V.M., assistant professor in Research Resources Facilities. “We have three rooms, so we can rotate groups of masks in each room, moving the VHP generator from one room to another.”

Each time a room full of masks is treated, biological indicators placed in the room are tested to ensure the VHP levels were sufficient to kill the virus, a step requiring an additional 24 hours. The entire process will take about 48 hours.

Davison said the staff members and UofL administrators have dedicated their own time to set up the rooms, test the process and provide administrative support to create the program.

“Our staff has been essential and very willing to help. They have the expertise in using the equipment. We couldn’t have gotten to this point without our staff, much less moving forward,” he said. “However, to keep it going, we will rely on a group of paid UofL employees who choose to participate and health sciences professional student volunteers.”

The program requires individuals to transport the used masks, perform the decontamination process and quality assurance checks and repackage and redistribute clean masks to health care providers. UofL employees who have training in biomedical safety procedures have chosen to participate, and protective equipment and safeguards are in place to protect them. In addition, UofL professional students in the Schools of Dentistry, Medicine, Nursing and Public Health and Information Sciences are eligible to volunteer to deliver the decontaminated N95 respirators to participating facilities. A sufficient number of staff and volunteers have signed up to help and are being trained to launch the program. If demand grows, more staff will be needed.

Sherwood said many individuals and departments throughout the university have come together to create the program in just a few weeks, including the School of Medicine, Speed School of Engineering, which provided logistics, the Department of Environmental Health and Safety, led by Hildreth, and the Executive Vice President for Research and Innovation's office. In that office, Kevyn Merten, Ph.D., associate vice president for research and innovation, has navigated the legal, fundraising and participant details needed to get the program up and running.

“This is just one more example of the many members of the UofL community who have responded to urgent needs, working together and using our advanced research expertise and infrastructure to solve problems during this crisis,” said Kevin Gardner, Ph.D., executive vice president for research and innovation at UofL.

“Everyone that is involved in this really just wants to help the front-line health care providers,” Sherwood said.

The N95 Decontamination Program has been awarded a $50,000 grant from the One Louisville: COVID-19 Response Fund that will support operational costs of the program. However, since there is no charge to the hospitals and other participating organizations, donations are gratefully accepted to help further defray the costs of equipment and supplies.

 

 

April 23, 2020