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Vital Signs
Vol. 43, No. 1 Summer 2022
18
Artificial
Intelligence
Research
to help medical students
get better feedback
Discovery 04
The Boonshoft School of Medicine and Wright State Gene Therapy
University have been recognized as a hub for cutting-edge for Canavan disease
research impacting people and communities in our area and
around the world.
From the Dean What’s Inside
T Vital Sign
he Boonshoft School of Medicine and Improving health outcomes affects the overall
Wright State University have been health of our communities. Examining biases
recognized as a hub for cutting-edge research that may exist in health care, and their effect on
4 12 16 22
impacting people and communities in our area health outcomes, is critical, and especially Vol. 44, No. 1
and around the world. important for those in medical education to Summer 2022
understand. Read how two BSOM OB/GYN
Upon my arrival to the Boonshoft School of
professors and physicians collaborated with Assistant Vice President
Medicine (BSOM) over a year ago, I developed a Issue in Depth Faculty in Focus Research In Good for Advancement
colleagues from medical schools across the Spotlight Company Angela Clements, C.P.A.
vision for the next decade by focusing on Robert Lober, M.D., Clintoria Williams,
country to research, create, and share best Editor
providing an even greater impact on the Ph.D., uses gene Ph.D., receives Forming better Juliann Althoff, M.D.
practice strategies for incorporating health equity therapy to help international differential leads reasearch in Angela Clements, C.P.A.
community and those we serve. Building upon acclaim for
into medical education. patients with diagnoses extreme conditions. Assistant Editors
our research infrastructure to yield increased Canavan disease. her research. using metamemory. Andrew Call
medical discovery is one very important way Fewer than 15 percent of medical schools offer a Nicki Crellin
Katie Halberg
BSOM can achieve that vision and improve the research track in orthopedics, and BSOM is one
Writers
health and life of people in the Miami Valley and of them. Learn how BSOM’s elective research
Tom Byerlein
beyond. Research is also a primary pillar of residency program in orthopedics has Lisa Coffey
BSOM’s overall strategic plan, and factors significantly boosted research production and Micah Elaine Karr
greatly into the direction of the school in the near our national visibility. This program is producing A Closer Look 8 Fond Farewell 26 Photography
A passion for biochemistry research Erin Pence
and distant future. excellent surgeons with an understanding of Chris Snyder
could help people with muscular
evidence-based medicine through research Mark Your Calendar 28 Design
Charles Kettering, one of Dayton’s disease.
experiences. Read how students are also Josh Trippier
entrepreneurial trailblazers from the last century, Using mortality and morbidity
benefiting from the residents’ work. How to contact us:
said, “research means that you don’t know, but conferences to help examine bias
and improve health outcomes
On The Move 29 Editor, Vital Signs
are willing to find out.” Like the great generations We all understand that it’s not always what is Wright State University
Boonshoft School of Medicine
of Dayton scientists whose work precedes us, said, but rather how, that matters. Several 3640 Colonel Glenn Hwy.
our BSOM community engages in this activity BSOM students discovered this when they 1,000 Words 14 Alumni Notes 30 Dayton, Ohio 45435
every day and is making great strides in patient learned the method of delivery of COVID-19 937-245-7634
care and treatment of disease. In this issue of information, particularly to people for whom In Residence 20 som_adv@wright.edu
Vital Signs, I am proud to highlight some of English is not their primary language, affected medicine.wright.edu
The benefits of an orthopaedic
these efforts. trust in the accuracy of the information. This research residency program.
research can help the medical community best To submit Class Notes:
We share a story about a professor in
share health information with refugees. som_adv@wright.edu
biochemistry building on her postdoctoral work Future Docs 24 937-245-7634
with muscle disease by investigating the role of a As BSOM enters its fifth decade, right now is an Student researchers find the best Vital Signs is published each year
protein deficiency in patients with Duchenne important time. Abraham Lincoln said, “The most way to reach refugees and for alumni, faculty, staff, and friends
immigrants with of Wright State University Boonshoft
muscular dystrophy. Her research could affect reliable way to predict the future is to create it.” School of Medicine.
COVID-19 knowledge
the development of new therapies for patients The people and work highlighted in this issue are © 2022 Wright State University
with this disease and similar muscle- helping BSOM create our future and attain Boonshoft School of Medicine
wasting conditions. strategic goals and, more importantly, fulfill the
hope for a better future for those in our View Vital Signs online at
A nearly 20-year journey led a neurosurgeon to
community and beyond. medicine.wright.edu/vitalsigns
BSOM as a professor of internal medicine and
neurology, bringing with him research leading to
Stay up to date between issues
a first-in-human clinical trial for Canavan disease,
by following the Boonshoft
a first for Dayton Children’s Hospital. Learn how School of Medicine online:
this trial is affecting the quality of life for impacted
children in the United States and abroad.
Valerie D. Weber, M.D., M.S.
2 Vital Signs Summer 2022 medicine.wright.edu 3
Issue In Depth
Gene therapy I n April 2021, a 4-year-old underwent a novel brain surgery at “I sort of fell into this work, with the right people at the right
Dayton Children’s Hospital. With four catheters inserted time,” said Janson. While working in During and Leone’s lab, a
through the little boy’s skull, the surgeon injected into his brain somewhat serendipitous event occurred. Two infants from
a fluid containing over 37 trillion viral particles, each containing Connecticut and New York were diagnosed with Canavan
for Canavan
DNA for a human gene, a first-of-its-kind experimental gene disease. The families, devastated and desperate to help their
therapy for Canavan disease. For comparison, this huge children, were aware of During and Leone’s work with gene
number of microscopic particles injected into the brain is even therapy and offered to provide funding for Canavan
more than the number of stars in the Milky Way galaxy. disease research.
Canavan disease is a rare genetic neurological disease that The families, the Karlins and Sontags, started several nonprofit
disease
typically presents in infants between 2 and 12 months of age. It research foundations and raised significant funds, which gave
destroys vision, speech, and motor functions. Symptoms the research momentum. “Quickly, we went from knowing the
include seizures and an abnormally large head, which appears gene responsible for Canavan existed, to cloning it in the lab,
floppy due to poor head control. and creating a viral vector suitable for use in a human. Literally
bench to bedside in two years,” said Janson.
Reported worldwide, Canavan disease is more frequently found
in children of Ashkenazi (Eastern European) Jewish decent, The initial procedure involved a nonviral vector called LPD,
when both parents are carriers of the gene that causes the made with a collaborator at the University of Pittsburgh, but
disorder. Though the precise prevalence is unknown, there are later iterations used the adeno-associated viral vector (AAV), a
Dayton Children’s Hospital is estimated to be fewer than 500 children with Canavan disease very small nonpathogenic virus that does not cause illness, to
the first in the world to use a new today in the United States. Most do not live past age 10. deliver small amounts of genetic material to neurons in the
brain. In 1996, New Zealand native During traveled to his home
The experimental surgery was performed by Robert Lober,
gene therapy to treat a patient M.D., Ph.D., an associate professor with the Department of
country to oversee the first human gene trial for Canavan
disease with the nonviral vector on Lindsay Karlin. Two years
Pediatrics at BSOM and a pediatric neurosurgeon with Dayton
with Canavan disease, which Children’s Hospital. Assisting Lober was Christopher Janson,
later, During, Leone, and their team performed the same
procedure in the United States on Jacob Sontag.
M.D., assistant professor in the BSOM Department of
earned national attention. Neurology, and assistant professor with the Department of Results were positive from both procedures. Karlin showed
Neuroscience, Cell Biology, and Physiology at Wright State and improved vision and better head control, and the Sontags
BSOM. Janson is also a neurologist with Premier remarked their son was like a completely new person. This
Health in Dayton. garnered media attention. In 1998, The New York Times
Magazine published a story about the Karlins and Sontags
Janson and Lober are the co-principal investigators on a
funding the research, the outcome of the procedures, and the
Canavan disease clinical trial, a first-in-human clinical trial taking
work being done by During and Leone. Sontag and his mother
place at Dayton Children’s. The two connected on the trial in
were featured on the cover.
2019, but it is work that has been in the making for
nearly two decades. THE GAME-CHANGER
THE RIGHT PEOPLE AT THE RIGHT TIME Following graduation from medical school, Janson deferred
residency to work in a post-doctoral position in human gene
In the 1990s, Christopher Janson was a student at the Yale
therapy with During and Leone. In 2000, they relocated to
School of Medicine, and the gene responsible for Canavan
Thomas Jefferson Medical School in Philadelphia. Janson
disease had just been discovered. Gene therapy, especially for
helped secure funding from the National Institutes of Health
neurological disorders, was still a new concept. A pair of Yale
(NIH) to continue their human gene therapy research for
researchers, Matthew During, M.D., and his associate Paola
Canavan disease, together with private foundations.
Leone, Ph.D., were working on gene therapy for Parkinson’s
disease. Janson’s interest in gene therapy and neurosurgery Gene therapy trials on children continued using AAV, which
drew him to their research, and he began working in their lab. were also in preclinical testing for Parkinson’s disease. During
During and Leone would later become his mentors. 2000–05, Janson and Leone collaborated on an NIH-funded
clinical trial, the first gene therapy for a neurodegenerative
4 Vital Signs Summer 2022 medicine.wright.edu 5
Issue In Depth
disorder, spearheading other work in the field. They saw Medicine, spent the next few years preparing for the new trial.
improvements in behavior, such as fewer seizures, but patients He helped to secure preliminary funding, designed the clinical
were not being cured. The trials proved they could change the protocols, and worked with a new clinical team on obtaining
biochemistry of the brain, a very important finding, but they approvals from the Food and Drug Administration (FDA). The
were not able to target the primary cells of interest due to Landsmans founded the Cure Canavan Fund in to help raise
limitations of viral vector technology at the time. money, and additional children joined the Landsmans as
trial participants.
Canavan disease is known as a leukodystrophy, because the
so-called white matter is primarily damaged. White matter Additional FDA requirements and issues with institutional
consists largely of myelin, a protective sheath for the brain, support created unexpected delays and significantly increased
Robert Lober, M.D., Ph.D., (top left) and Christopher Janson, M.D., (top right) with the Pronin family,
required for effective neurotransmission. A mutation to the the costs. Janson and the families, ready to move forward, including (lower left to right) son Artyom, mother Alla, and son Sergei. The family traveled from Russia
ASPA (aspartoacylase) gene affects the gene’s ability to were getting anxious. to Dayton, where Artyom was successfully administered gene therapy on May 17, 2022.
properly break down the enzyme NAA (N-acetyl-L-aspartic
DAYTON—THE PERFECT FIT
acid) which builds up, causing the myelin to fall apart. “The
brain becomes full of holes and waterlogged like a sponge,” Robert Lober, M.D., Ph.D., came to Dayton and BSOM in 2015 Dayton Children’s is the first hospital in the world to use this Inc., a gene therapy company in Massachusetts funding the
said Janson. Unfortunately, the first generation of viral vectors from California, where he was an assistant professor of new gene therapy on a Canavan disease patient, which earned continuing study. In 2021, Myrtelle entered into an agreement
had targeted neurons in the so-called gray matter, and neurosurgery with Stanford Medicine. “Right away, BSOM was national attention. Stories have appeared in People Magazine, with Pfizer, Inc. to develop and commercialize their patents on
selectively targeting white matter remained an elusive goal. interested in helping me get established with research,” said TODAY Show, and the Jewish Observer. The coverage led to AAV-based gene therapy. The company is named after Dr.
Lober. His research interests include pediatric brain tumors and further financial support for the trial. From May to June 2020, Myrtelle Canavan, the Harvard-affiliated pathologist who first
In 2016, a colleague of Janson and Leone discovered that People Magazine readers donated $200,000 to described the clinical disease.
using advanced imaging and molecular techniques to
changing one amino acid in the AAV capsid (or outer shell) the Landsmans.
develop treatments. Janson is proud of this trial. “We started this ourselves as a
drastically changed its behavior and the cells it targeted. They
were able to direct the new viral vector to oligodendrocyte cells, In 2019, Janson contacted Lober, whom he had met a few At regular intervals after surgery, the treated children will return kitchen table project, using patient funds to get it going and
essential for the production of white matter. Tested in animal years earlier during a facilities tour in Dayton. “I reached out to Dayton for assessments, checking their neurological status FDA cleared,” said Janson. “I’m confident that this gene
models, the new viral vector with ASPA, directed at the hoping he would remember who I was,” said Janson. He and development, measuring motor function and learning therapy will lay the foundation for future trials of many other
oligodendrocyte cells, cured Canavan disease in mice. Janson shared with Lober the details of the Canavan disease trial and capabilities appropriate with their age. The team is also using genetic diseases. There is already proof-of-principle, but a lot
and Leone published this latest and biggest discovery. This new his need to move forward. Lober immediately felt Dayton would advanced imaging to directly measure brain volumes and more work needs to be done before it becomes mainstream.
version of AAV gene therapy was anticipated to be a game- be a good location for Janson’s clinical trial. “The great facilities myelin content. The data collected is compared to identical The current position of gene therapy is analogous to the
changer. The discovery was licensed to Pfizer, which funded at Dayton Children’s Hospital, and BSOM’s desire to build and assessments done pre-surgery. position of aviation at the time of the Wright brothers. It will
additional research on viral vectors but opted not to support more research infrastructure—it’s the perfect definitely take off; it’s just a matter of time.”
Janson and Lober are pleased with how the children are
commercially develop Canavan gene therapy. fit,” added Lober. progressing. “Follow-up data in treated patients demonstrate Along with a treatment for Canavan disease, and providing
Soon after publishing their new findings in 2016, Leone, who Following a presentation on the Canavan disease trial by Leone favorable safety and tolerability with encouraging initial efficacy hope for the children and their families, Janson and Lober
was in New Jersey with Rowan University School of Medicine, and Janson, Dayton Children’s agreed to support the project. results,” said Lober in a February 2022 Businesswire.com story. believe information from this trial will help with developing
was approached by the Landsmans, a family from New York Janson arrived in Dayton from Chicago in December 2019, They are looking forward to continuing to progress with the treatments for more common diseases like Parkinson’s and
with two children recently diagnosed with Canavan disease. bringing with him a newly awarded NIH grant on the study and to perform procedures on more children. Alzheimer’s. Lober added, “This clinical trial puts BSOM and
They found Leone through social media and the article she pathophysiology of Alzheimer’s disease, which used some of Dayton, Ohio, on the world map, and extends our reach to help
Lober has been overwhelmed by the support from BSOM’s
published with Janson about the new viral vector the same recently discovered AAV technology proving many more people all over the world. I’m honored and grateful
clinical partners for the trial, and for the families when they
and gene therapy. successful curing Canavan in animal models. to do my part for these patients, in order to improve their lives
arrive in Dayton. Dayton Children’s even built a special space
and advance the state of the art of gene therapy.”
Similar to the families Leone had worked with before at Yale Although COVID-19 created another delay, by 2021 Lober and for clinical evaluation of trial participants. Lober added, “It has
—LISA COFFEY
and Thomas Jefferson, the Landsmans were desperate to help Janson were cleared to proceed. In April 2021, the procedure been awesome to see all the clinical partners align with the
their children, and offered to assist with funding if she would was performed on the Landsman’s oldest son Benny. Later that academic side on this!”
pursue a new Canavan disease clinical trial. Leone promptly spring it was performed on the younger sibling, Josh. In the LOOKING AHEAD
reached out to Janson, who agreed to be the lead physician for summer of 2021, a young girl from Italy also received the gene
therapy surgery. Leone was present for these procedures. In The investigators have heard from new patients and their
a new clinical trial in 2017.
May of 2022, the procedure was performed on a young families across the country and around the world, from North
boy from Russia. and South America, Europe, Asia, and the Middle East.
Janson, who was with University of Illinois–Chicago College of At this time, the investigators are collaborating with Myrtelle,
6 Vital Signs Summer 2022 medicine.wright.edu 7
A Closer Look
A passion for
gene therapy for DMD. “This will enable us to explore new
research directions and help patients with DMD and other
muscle-wasting conditions,” said Ren.
biochemistry research
The awards were received in collaboration with her research
team—Mark Rich, Ph.D., professor of neurology with BSOM,
and professor of neuroscience, cell biology, and physiology
with Wright State and BSOM; and Andrew Voss, Ph.D.,
associate professor of biological sciences at Wright State.
could help people
Ren joined the faculty at Wright State in 2016. “Wright State
has an ideal research environment, especially in muscle
research,” she said. Ren says she is inspired by the impact of
her work and enjoys sharing that inspiration. “I like to pass on
with muscular disease
my passion for biochemistry research to my students and help
them pursue their careers in biological science,” Ren said.
Many of her students have done remarkable and award-
winning research, and several work for pharmaceutical
companies, researching treatments for muscle disease.
“Biochemistry is a science exploring cellular mechanics of
various life processes. These insights can be applied via gene
therapy, and other avenues, to improve lives,” added Ren.
Ren completed her postdoctoral training with the
Cardiovascular Research Center at the University of Kentucky
and earned a Ph.D. from the Institute of Brain Chemistry and
Human Nutrition at London Metropolitan University. She earned
her undergraduate degree from London Metropolitan University.
Hongmei Ren, Ph.D.
“We have found lipin1
exploration of lipin1 as a novel alternative or complementary
therapy can reduce a wide gene therapy in dystrophic muscles.
range of symptoms, Ren said she has been approached often by families of patients
with muscle disease, hopeful her research can help improve the
Muscular dystrophy is a group of inherited diseases lead to the development of a treatment for DMD patients. improve muscle function, lives of their loved ones. “I am proud of what I am doing. I hope
characterized by weakness and wasting away of muscle tissue. my knowledge and research can help patients with DMD
and slow disease
Ren’s research focus is lipid metabolism and muscle
Duchenne muscular dystrophy (DMD) is one of nine types of increase their lifespan and improve their quality of life,” Ren
biochemistry and physiology. In a recent publication, Ren
muscular dystrophy, and one of four conditions known as
dystrophinopathies.
revealed the critical role of the lipin1 gene in maintenance of
progression of said, adding, “We may develop a treatment for
DMD.”—TOM BYERLEIN
muscle membrane integrity. She pointed out a deficiency in
Mutations in the gene coding for the protein dystrophin, lipin1 alone can lead to compromised muscle membrane dystrophic muscle”
responsible for maintaining the structural integrity of muscle integrity and myopathy, as seen in people suffering from
membrane cells, causes membrane leakage and muscle muscular diseases like DMD.
wasting. People with DMD suffer physical disability, immobility,
In 2021 Ren received an R01 grant from the National Institutes “We have found lipin1 therapy can reduce a wide range of
and, often, premature death. Currently, there is no cure.
of Health (NIH) National Institute of Arthritis and Musculoskeletal symptoms, improve muscle function, and slow disease
Research underway at Wright State by Hongmei Ren, Ph.D., and Skin Diseases, and an Idea Development Award from the progression of dystrophic muscle,” said Ren. The research
assistant professor of biochemistry and molecular biology, may Department of Defense—totaling $2.4 million—to research grant and awards Ren and her team received will enable further
8 Vital Signs Summer 2022 medicine.wright.edu 9
A Closer Look
Using mortality and Tufts Medical Center OB/GYN
department holds quarterly health equity
rounds during grand rounds. Department
the journal Obstetrics & Gynecology
that December.
10 recommendations
to incorporate
health equity
morbidity conferences to
“Institutions do things differently, but
faculty, nursing staff, residents, and
using the main premise behind the tips
medical students attend. Other
and tricks will help them reach a similar
departments are invited based on the • Avoid only selecting cases
goal,” added Reisinger-Kindle.
help examine bias and
topic. Sessions begin with a reflection that fulfill stereotypes
and take place within a “brave space,” a One of the group’s recommendations • Invite an inclusive and
space where participants can be open involves permitting active patient multidisciplinary list of
participation by inviting patients to
improve health outcomes
and honest, without judgement or fear of attendees
punishment. Interactive surveys allow physically be present at the conference,
• Lead discussions using a
those in attendance to be or directly sharing their words and
trained facilitator
polled anonymously. feelings. “Hearing from patients directly
prevents bias and gives them an • Create an environment
HEqR (health equity rounds) are a key
opportunity to call us out when we’re with a focus on “Just
component of the health equity program
V
wrong,” said Reisinger-Kindle. Culture,” an assumption
arious sources have published “Everyone is talking about health care of what each organization does to at Harvard Medical School’s combined
that those involved in
findings highlighting significant disparities within obstetrics and promote health equity during morbidity OB/GYN residency program at For Reisinger-Kindle, and the entire
providing care are
disparity in health outcomes between gynecology; people are very motivated to and mortality conferences. Massachusetts General Hospital and group, the hope is that sharing defined
intending to do their best
white patients and patients of color. address it, but very few know how,” said Brigham and Women’s Hospital. Cases goals for successful implementation will
BSOM OB/GYN organizes health-equity-
Maternal mortality and morbidity continue Keith Reisinger-Kindle, D.O., OB/GYN are selected by residents, with approval allow other institutions to apply health • Center the patient’s voice
specific morbidity and mortality
to occur at unacceptably high rates in faculty at BSOM and OB/GYN physician from department quality, diversity, equity, equity analyses into their educational and permit active patient
conferences quarterly, in addition to
the United States, and rates are with Wright State Physicians (WSP). and inclusion leadership, from conferences, to continue to address participation
regularly scheduled morbidity and
significantly higher among communities suggestions provided by clinical staff, or inequities in care as a community Analyze beyond implicit
This realization, and an intense interest in mortality conferences. Residents, •
of color. Even when adjustments are via the anonymous “(In)Equity Inbox.” and a profession. bias
addressing social injustice and its effects medical students, faculty, nursing staff,
taken into consideration for confounding
on health care and patient outcomes, and social workers attend. Following a At the University of Massachusetts Reisinger-Kindle added, “We need to be • Be purposefully
factors, such as socioeconomic status,
inspired Reisinger-Kindle to create a discussion of case details and didactics, Memorial Medical Center, health equity learning from the bad outcomes, of intersectional, understand
health outcomes for black patients are
model to incorporate equity into the format becomes primarily interactive, analysis has been built into the OB/GYN course to prevent them, but also with a the complexity of
still worse than those for white patients.
morbidity and mortality conferences. with small group breakouts and activities, monthly departmental morbidity and new perspective that centers on bias to prejudices a patient may
Mortality and morbidity conferences, such as social identity wheel mapping, mortality conferences. Before presenting create better outcomes. My biggest fear face, and be aware to not
After unofficially discussing this issue and
which are departmental reviews of cases privilege walks, and analytical a case, residents are given guidance [is that] we keep talking about it, but use language, in chart
sharing best-practice health equity
with less-than-ideal outcomes, have long dialogue sessions. from the department’s director of things never get any better.” notes for example, that
activities among colleagues for nearly a
been a part of medical education in diversity, equity, and inclusion on may bias other providers
decade, Reisinger-Kindle officially Cases at BSOM are chosen by faculty Reisinger-Kindle, who is formally trained
nearly every specialty. They first took identifying opportunities to advance toward the patient
organized a group in 2021. Included in trained in anti-racism education, social as a social justice and anti-racism
place in 1904 with the evaluation of health equity from details within the case.
this group was fellow WSP OB/GYN justice dialogue facilitation, and social facilitator and educator, initiated anti- • Acknowledge the full
surgeon competence.
physician David Dhanraj, M.D., BSOM identity-based conflict resolution, and A review of the activities of each racism dialogue training for the OB/GYN spectrum of racism’s
Given the central role that morbidity and chair of OB/GYN and newly appointed alternate between obstetrics and organization resulted in a list of 10 residents in 2019, soon after joining harmful effects
mortality conferences play in medical associate dean for clinical affairs. Other gynecology cases, to allow for sufficient recommendations, “tips and tricks” as BSOM as an OB/GYN professor and • Identify ways to interrupt
education and quality improvement, they members represented various leading depth of case and topic analysis. Reisinger-Kindle refers to them, or a associate director of the OB/GYN problematic systems
serve as a natural stage for the health care organizations, including Previous topics have included: framework to use for building a mortality residency program. Since that time, the
examination of systematic inequities in Massachusetts General Hospital, Introduction to Language and Concepts: program has rapidly grown, more • Organize post-session
and morbidity conference format that
health care. There has been an Brigham and Women’s Hospital, Tufts Examining Racism Beyond Implicit Bias, facilitators are being trained, and debriefs and feedback
incorporates principles of health equity.
increasing desire to incorporate an equity Medical Center, and University of How Racism Impacts Housing Inequities This list, with additional supporting offerings are being made available to
component into these conferences. Massachusetts Memorial Medical Center. and Worsens Health Outcomes, and documentation, was submitted to The more BSOM faculty, staff, and
Despite the desire and drive, there is little Language Matters: How American College of Obstetrics and students.—LISA COFFEY
The group began what would be a
published guidance around “Microaggressions” Result in Gynecologists in 2021 and published in
six-month process that started with
best practices. “Macro” Inequities.
documenting and comparing examples
10 Vital Signs Summer 2022 medicine.wright.edu 11
Faculty in Focus
Clintoria Williams’
research receives
international acclaim
C lintoria R. Williams, Ph.D., FAHA, is
part of an up-and-coming group of
biomedical researchers. She has been
Williams is an assistant professor in the
Department of Neuroscience, Cell
Biology, and Physiology and the director
could serve as the foundation for new
treatments and drug targets for both
hypertension and kidney
featured on the cover of The Physiologist of the Small Animal Physiology Core. She disease as a whole.
Magazine, an international publication of has been with Wright State since 2018
Chronic kidney disease and hypertension
the American Physiological Society. This and has played an integral part in helping
are frequently accompanied by a
is one of many achievements for her students grow into competent,
deficiency in zinc, which can have
Williams, who made national and effective researchers. She works hard to
negative consequences on the
international news with her research that raise marginalized voices Left: Clintoria R. Williams, Ph.D., FAHA. Top right (from left to right): Kajal Davi, Ryan Elam, and Clintoria Williams. Bottom
cardiovascular system and inflict further
has linked zinc deficiency to high within medicine. right (from left to right): Kajal Davi, Tara-Yesomi Wenegieme, B.Sc., Clintoria Williams, Ph.D., FAHA, Ryan Elam, and
damage to the renal system. Williams’
blood pressure. Cindellynn K Rudy.
Williams’ research is centered around research determined that hypertension
The Physiologist Magazine named cellular and molecular physiology, induced by zinc deficiency is a
Williams as among the “now” generation vascular pathophysiology, and renal consequence of kidney dysfunction.
publications. Williams said that seeing calcineurin is not a singular protein with a In 2017, she was a participant in the
of scientific researchers. Her research pathophysiology. She has published 16 Specifically, Williams has found that
her students succeed is encouraging. singular function. By selectively Research Leaders Academy for the
has been published in the American articles on a variety of topics including dietary zinc restriction in animals
She is looking forward to continuing to modulating calcineurin’s activity, it could American Heart Association. She was
Journal of Physiology – Renal Physiology, the role of immunosuppressive drugs in promotes hypertension by driving renal
work alongside others to increase be possible to preserve the kidneys while named a fellow of the American Heart
and her lab’s findings have been featured causing cancer and kidney disease, the sodium retention. This was reversed by
diversity, inclusion, and equity in the maintaining immunosuppression. Association and served on the Council
in articles by Science Daily, Medical effect of zinc on the kidneys, and the replenishing the diet with zinc. These
scientific community. on the Kidney in Cardiovascular Disease.
News Today, Cardiovascular Business, effect of nutritional intervention on significant findings establish the To Williams, research is only half of her
and The Health Site, among others. kidney health. physiological role of zinc in blood Williams said that her long-term research passion. She is also incredibly dedicated Along with her appointed positions, she
pressure control and highlight a novel goal is to reverse or prevent hypertension to bringing minority voices and has also received a variety of awards. In
Williams gained recognition through her Williams’ research examines
approach to blood and slow chronic kidney disease. Her lab perspectives to research and 2017, she received the PhUn Week
experiments and data generation, which hypertension, a major risk factor in
pressure management. has pioneered the understanding of development of treatment. She is Five-Year Participant award from the
earned her a National Institutes of Health chronic kidney disease progression,
zinc’s role as a diet-related regulator of currently the president of Black in American Physiological Society. In 2020,
scholarship and Minority Access to which leads to end-stage kidney failure. Currently, Williams works with a team of
renal blood pressure homeostasis. Physiology Inc., a nonprofit organization she was granted the Faculty Award for
Research Careers for Undergraduate Uncontrolled blood pressure is still undergraduate, M.D., and Ph.D. students
that promotes Black scientists in Excellence in Early Career Achievement
Students Training in Academic Research present in almost 90 percent of chronic to assist with research. Williams’ Alongside her students, Williams has
physiology-related fields. The group by Wright State University. In 2021, she
(MARC U* STAR). kidney disease patients despite the philosophy of “lifting while she climbs” worked to study calcineurin inhibitors, a
encourages conversations around received the Renal Section Young
availability of several types of drugs that has enabled her to help K–12 students vital immunosuppressive therapy in the
“Taking biology lab courses as an diversity and inclusion in the field of Investigator Excellence in Research
combat hypertension. To combat this, along with her research team. Williams’ management of conditions that could
undergraduate student birthed an physiology. Additionally, she is the Award from the American Physiological
Williams’ lab has worked to identify students have won scientific poster cause inflammation. Calcineurin inhibitors
appreciation of science and the president of the Dayton American Society.—MICAH KARR
cellular and molecular mechanisms that awards and travel awards to national often cause major side effects that can
interesting and provocative questions Heart Association.
drive hypertensive kidney damage. scientific meetings. Her students have lead to kidney damage and hypertension.
that remained unanswered,”
Exploiting the underlying mechanisms significantly contributed to a variety of Williams’ research has found that
Williams said.
12 Vital Signs Summer 2022 medicine.wright.edu 13
1,000 Words
F aculty, residents,
graduate students, and
medical students gathered in
the Wright State University
Student Union Apollo Room on
January 6, 2022, to present their
research at the annual Boonshoft School
of Medicine Research Symposium.
14 Vital Signs Summer 2022 medicine.wright.edu 15
Research Spotlight
diagnosis could save $100 billion per year in unneeded tests, students were asked to mentally “dissect” patients from
wrong treatments, and malpractice lawsuits. front to back, asking “What lives here?” and “What can go
wrong with it?”
Honing diagnostic skills is a lifelong pursuit, but BSOM
researchers have found the use of mental shortcuts can • Bundling: A cue to remind the students that “diagnoses
improve novice doctors’ ability to form differentials. travel in packs.” That is, sometimes a diagnosis for a given
scenario is associated with other diagnoses. “Once you
“There’s a school of thought that says the only way you get
get one,” Leeds said, “you get the others for free.”
better at DDx is to do it a whole lot,” Leeds said. “We don’t
believe that. We think we can figure out what experts are doing • Constellation: A pattern recognition tool to generate
and make it teachable.” differentials from various constellations of medical findings.
BSOM researchers have developed a three-step model of DDx. • V.I.N.D.I.C.A.T.E.S.: A mnemonic to remind students to
First, doctors intuitively generate a list of possible diagnoses. consider various diagnoses by pathophysiology. It stands
Then they filter out implausible diagnoses and order the for Vascular, Inflammatory, Neoplastic, Degenerative,
remaining diagnoses for likelihood and risk to patients. Idiopathic/Iatrogenic, Congenital, Autoimmune/Allergic,
Trauma/Toxic, Endocrine/Electrolyte/Electrical, and
“If you don’t get generation right, the rest of it falls apart,”
Social/Psychiatric.
Leeds said. “That’s the stumbling block for most students.”
Students were limited to three
The problem likely isn’t a lack of knowledge. “By the third year
minutes to generate
of medical school, the average student has acquired an
differentials in each case. “It
impressive reserve of clinical knowledge,” BSOM
was very rapid-
researchers wrote.
fire,” Leeds said.
Forming better “The problem is not knowledge,” Leeds said. “The problem is
access to knowledge.”
The BSOM researchers found that third-year medical students
Researchers determined
differential sizes by the raw
number and by those
differential diagnoses made broader and better differentials when they jogged their
memories with metamemory techniques, or MMTs.
comporting with a list of
medically
plausible diagnoses.
The ongoing research began in 2018, when a full class of
using metamemory BSOM’s third-year family medicine clerkship students was
evaluated over an academic year.
The study showed that
students using the Mental CT
Scan generated a statistically
Researchers asked the 114 students to generate differentials
for fictitious cases based on common clinical scenarios. They significant increase in
differentials over those who
A mong the most common—and serious—types of medical constitutes a significant percentage of such errors. paired the eight cases so students generated differentials
before and after receiving training in each of four MMTs. didn’t. There also appears to be a cumulative improvement
errors are failures of diagnosis. Sometimes these errors
“A failure to generate adequate and appropriate differentials is a when the other MMTs are used.
occur because doctors don’t even consider the proper “Students and educators often think of MMTs as gimmicks or
likely root cause of diagnostic error—and such errors frequently
diagnosis on their mental lists of possibilities. ‘tricks,’ but such devices have been shown to enhance Benefits of the “weaker” MMTs may be statistically significant in
put patients at risk,” according to a 2020 article by Leeds and
academic performance in a variety of settings,” the BSOM a larger study, researchers said.
Researchers at BSOM are studying how well young doctors his team. They cited estimates that “in the U.S. outpatient
can expand those lists of differential diagnoses by using mental population alone, perhaps 12 million patients a year are research noted. BSOM researchers are now working on a “big kahuna”
techniques to help them access memories from their exposed to errors in diagnosis, half of which result in The researchers wrote that the four MMTs under study were theoretical model paper and Leeds is writing a book
medical training. measurable harm.” chosen “based on their broad applicability, apparent common on the topic.
Frederic Stuart Leeds, M.D., an associate professor of family Research shows that wrong or delayed diagnoses cause more usage in clinical settings, and the teaching experience of the The MMT training has proven popular with students, who said
medicine at BSOM who is leading this differential diagnosis harm to patients than any other kind of medical error, resulting authors, as well as on the relevant literature.” the Mental CT Scan was particularly useful.
(DDx) research, said, “failures of diagnosis are a tremendous in 40,000–80,000 deaths annually in U.S. hospitals. The The four MMTs studied by researchers were: “I want them to walk out thinking, ‘I’m a better doc for this and
clinical problem,” and “failure to entertain the proper diagnosis” Society to Improve Diagnosis in Medicine said improving
• Mental CT Scan: A visualization technique in which they didn’t waste my time,’” Leeds said.—TOM BYERLEIN
16 Vital Signs Summer 2022 medicine.wright.edu 17
Research Spotlight
Artificial intelligence could
help medical students get
better feedback
S tudies have shown that doctors can
be more effective when they ask
better questions and let patients do more
Motivational interviewing doesn’t
preclude doctors from educating and
advising patients, but it puts more
ReadMI stands for Real-time Assessment
of Dialogue in Motivational Interviewing.
ReadMI uses the low-cost, highly
of the talking. But, too often, doctors fall emphasis on leading patients to express
accurate Google Cloud Speech app to
back on the practice of educating and their health concerns and make plans
transcribe interviews, and analyze the
advising patients when the situation calls for improvement.
transcripts to evaluate how well doctors
for better listening.
In addition to open-ended questions, MI are using the MI approach. ReadMI
Researchers at BSOM are now using the emphasizes the use of reflective “produces a spectrum of metrics for MI
latest in artificial intelligence statements designed to elicit a response, skills evaluation, including the number of
technology—a computer application they such as “You’re very concerned about open- and closed-ended questions
call ReadMI—to provide better feedback the possibility of developing diabetes,” asked, provider versus patient
to medical students and residents on followed by a pause for a patient conversation time, number of reflective
their use of motivational interviewing (MI) response. Another MI technique is asking statements, and use of a change ruler
when talking with patients. The patients to use a scale of 0–10 to rate (the 0–10 scale)...eliminating the need for
researchers say their work “has the importance, readiness, or time-consuming reviews of recorded
potential to transform MI training” and confidence about change. training sessions,” according to the
improve the quality of health care. scholars’ research.
Hershberger said MI has been shown to
The conversations were transcribed and spends talking, the fewer open-ended In the future, project leaders Hershberger,
MI is patient-centered conversation in be effective in motivating patients since Automating the transcription and some
analyzed by ReadMI. Five human MI questions they ask.” That was also true Pei, and Dean A. Bricker, M.D., a BSOM
which physicians speak less and ask its introduction in 1983, but “it’s never of the analysis of doctor-patient
training facilitators also read the of other MI metrics. associate professor of internal medicine,
more open-ended questions designed to been widely implemented. Telling patients conversations greatly speeds the
transcripts and rated the physician hope to see ReadMI become even more
strengthen patients’ motivation and what to do seems easier and gets process and frees faculty to evaluate the A forthcoming paper based on a
utterances. Overall, there was moderate automated, accurate, and user-friendly
commitment to make healthy lifestyle modeled in the clinical setting.” spirit of the conversation, which can’t be randomized, controlled trial of 120
agreement of 33.3 percent between for faculty. They also hope for real-time
changes. Physicians using MI guide graded by a machine, Hershberger said. medical students will report that students
MI training can be time-consuming, ReadMI and the human raters, but analysis so doctors can see their MI
patients toward taking charge of asked significantly more open-ended
Hershberger explained, because it The initial BSOM research in 2019 used ReadMI was more than 90 percent metrics on screen during consultations.
improving their health. questions if ReadMI was employed in
involves transcribing and evaluating ReadMI to analyze 48 role play accurate in producing transcripts,
interview feedback, Hershberger said. BSOM introduces motivational
Paul J. Hershberger, Ph.D., a BSOM interviews to quantify doctors’ use conversations between simulated discerning open-ended and closed-
interviewing during students’ first two
professor of family medicine, noted that of MI skills. patients and residents in family medicine ended questions, and isolating physician- Yong Pei, Ph.D., LexisNexis Ohio
years, and provides training in the family
the U.S. “spends more on health care, and internal medicine. The simulated and patient-speaking time. It was weaker Eminent Scholar and professor of
That’s where ReadMI comes in. BSOM medicine, clerkship and in several
but we actually have poorer outcomes patients presented prepared scenarios to in recognizing reflective statements. computer science at Wright State,
researchers, in partnership with the residency programs.—TOM BYERLINE
than most developed countries, residents, including a patient requesting helped to develop ReadMI. He said
Wright State College of Engineering and “A significant, negative correlation was
particularly in chronic disease morbidity. more opioid pain medication and a ReadMI was especially accurate in online
Computer Science, developed the found between physician-speaking time
That suggests we should pay more and member of the clergy using marijuana to interviews, which makes it a good fit for
training tool to automate the process of and the number of open-ended
better attention to patients’ responsibility cope with stress. telehealth visits.
transcribing and evaluating MI interviews. questions asked,” according to the study.
in their health care.”
“That is, the more time a physician
18 Vital Signs Summer 2022 medicine.wright.edu 19In Residence
The benefits of an
particular career path, so if research peer-reviewed articles, up from 52 program began. Those results are not in,
residents end up in academic positions, percent prior to the research residency. but Froehle said, “by and large, I think it’s
that’s great. But if they go into general going to mirror what we’ve seen with
“The productivity of publication has shot
practice in a rural community, that’s just the residents.”
orthopaedic research
up, and that’s true of the research
as great in our eyes,” Froehle said.
residents and the non-research A review of BSOM’s scholarly activity in
“We want to train excellent surgeons residents,” Froehle said. “It 2021 shows there were 19 publications,
who also have a clear understanding of benefits everyone.” a book chapter, four national
residency program
presentations, eight regional
presentations, and five state and local
presentations.
“The importance of research exposure BSOM’s research residents have
undertaken a host of studies covering a
and education during orthopaedic gamut of topics related to the treatment
of musculoskeletal injuries and diseases.
residency has been discussed at length Among the research: clinical case
over the past few decades.” studies, injury modeling, whole-body
motion analysis related to injury
prevention, studies on clinical outcomes,
and approaches to using hardware like
screws and plates to repair bony injuries.
evidence-based medicine via their
In addition, the program has led to They also have done research into
research experiences. How they apply
broader participation in research by resident education itself.
the skills and knowledge in their careers
others in the BSOM community. Ten to
after they leave is up to them.” “Breadth is our strength—being able to
15 medical students per academic year
do a wide variety of research,” Froehle
According to the article in the Journal of participate in the research residents’
said.—TOM BYERLEIN
Bone and Joint Surgery, “The importance work, giving them experience in research
of research exposure and education and enhancing their curricula vitae.
during orthopaedic residency has been
This experience in research gives
discussed at length over the past few
B SOM is making a name for itself in
orthopedics research, in part
because of its research
Andrew W. Froehle, Ph.D., a BSOM
associate professor and the research
director of the Orthopaedic Residency
not very strong in our research
production,” Krishnamurthy said. The
research residency program has done “a
decades.” The Accreditation Council for
Graduate Medical Education requires
participating BSOM students better
chances of matching with an orthopaedic
residency program in a highly
that orthopaedic residency programs
residency program. Program since 2016. Because of the tremendous amount of good in terms of competitive environment.
incorporate research into their curricula.
program, BSOM is represented at more research productivity.”
BSOM is among fewer than 15 percent “However, the many challenges The program has been popular with
national and regional research meetings
of medical schools in the United States The program added two orthopaedic associated with completing meaningful residents, Froehle said. “People want it
than it was in the past.
to offer a research track in its orthopedics research residents per year in addition to research in a surgical residency have expanded to conduct more and
program. According to a 2019 article in The program “just creates a culture of two categorical residents. The research been well described, including limitations larger studies.”
the Journal of Bone and Joint Surgery, research being more central to residents take a year of protected in time, experienced mentors, research Although there are no plans to add
only 23 of 196 U.S. orthopedic residency residency” at BSOM, Froehle said. research time after their intern year, for a infrastructure, and research funding,” research residency slots, BSOM’s recent
programs include a research track. six-year course instead of the the article said.
Anil B. Krishnamurthy, M.D., director of addition of faculty members—and plans
customary five years.
The addition of the elective research the Orthopaedic Residency Program, BSOM is tackling these challenges with to add more—will also mean greater
residency program in 2008 has said BSOM launched the research These residencies are not particularly its research residencies. diversity in research areas.
significantly boosted BSOM’s orthopedic residencies in 2008 when a previous aimed at those who want to go on to
A recent review by BSOM researchers BSOM is currently studying whether
research production and consequently research fellowship was folded. academic careers.
shows that 86 percent of all BSOM faculty research activities have also
increased its national visibility, said
“One of our weaknesses was we were “We don’t look for people pursuing any orthopaedic residents are now publishing increased since the research residency
20 Vital Signs Summer 2022 medicine.wright.edu 21In Good Company
Optimizing readiness University before she graduated from the Boonshoft School of
Medicine in 1995 and completed her flight surgeon training in
and performace in
1997. She received her Master of Public Health degree from
the Uniformed Services University in Bethesda, Maryland, and a
Master of Arts degree in national security and strategic studies
extreme enviroments
from the Naval War College in Newport, Rhode Island. In 2005,
she completed a residency in general public health and
preventative medicine at the Uniformed Services University.
She then served in Okinawa, Japan, where she created a
J uliann Althoff, M.D., an Ohio native, has traveled the world toxic fume exposure, as well as evaluation of the combinations biohazard response plan for the U.S. Pacific Command, which
throughout her medical career. She has served and lived in of stressors. NAMRL efforts include acceleration, spatial became the blueprint for the way the Department of Defense
Japan, Spain, and over 13 other locations throughout the disorientation, hypoxia, fatigue, motion sickness, vision (DOD) responded to the H1N1 pandemic, also known as the
world. She has served as the senior flight surgeon for Marine standards, and performance. Swine Flu, in 2009.
One, the presidential helicopter squadron. Now, she has From 2016 to 2019, Althoff served as executive director of the
Within these areas, NAMRU-D works to ensure that safety
returned to Dayton to continue assisting in research and to Defense Health Board. She led the DOD’s only federal advisory
policies and standards match with current research about
oversee operations for the Naval Medical Research Unit committee on health. She assisted in developing two reports
exposure and workplace hazards. They also develop
Dayton (NAMRU-D). on pediatric health care and low-volume, high-risk surgical
technology to ensure officer safety.
Althoff serves in a leadership position for NAMRU-D, where her procedures. These reports provided hospitals with information
For example, NAMRU-D developed and tested goggles for the
mission is to optimize the readiness, performance, and that improved care opportunities. The committee was made up
coast guard. These goggles will protect pilots from lasers fired
survivability of operational forces through environmental health of civilian experts and specialists, who assisted the DOD to
at them in an airplane cockpit. “This was a real problem,”
effects, toxicology, and aerospace medical research and examine areas of interest in the world of health. Althoff said the
Althoff said. “Our lab was able to be part of the solution and
development. “We really focus on performance in extreme expertise on the board was expansive. “It was amazing to be
provide the solution.”
environments,” Althoff said. part of the committee,” Althoff said. “The caliber of the people
Althoff has also worked to assist in fighting the ongoing on the board was shocking, it was a wonderful
NAMRU-D consists of two labs, the Environmental Health
COVID-19 pandemic. Before she was stationed in Dayton at role for advising.”
Effects Laboratory (EHEL) and the Naval Aerospace Medical
Wright-Patterson Air Force Base, she was the chief medical
Research Laboratory (NAMRL). EHEL efforts include evaluation Althoff said she is glad to be back in Dayton and is happy to be
officer for the Naval Medical Center in San Diego. Before the
of chemical, physical, and environmental stressors such as working with NAMRU-D. Her labs work with over 54 partners,
COVID-19 vaccine was available, Althoff used other
including NASA, Wright State, and other educational
preventative measures, such as masking, social distancing,
institutions. “These partnerships are essential and highly valued
hygiene, and avoiding large social gatherings, that were proven
aspects of successful research and development efforts,” she
effective during the 1918 flu pandemic to protect her staff
said. “We work with a lot of people who are graduates from
and colleagues.
Wright State. It’s been fantastic.”
Along with her colleagues, Althoff ensured that patients
Althoff said she has enjoyed reconnecting with the BSOM and
received the best possible care though quality assurance and
the Wright State alumni society. She enjoys seeing how far the
patient safety initiatives. As the chief medical officer, Althoff
medical school has come and is proud to see the direction the
oversaw coordinating treatment efforts and she worked hard to
school is taking.—MICAH KARR
ensure that each office and branch provided the highest quality
of service to their patients, along with keeping staff safe by
utilizing more virtual appointments and avoiding in-person
contact when possible.
Ever since she was young, Althoff wanted to be a doctor. She
was inspired by her grandfather, who passed away during the
flu pandemic in 1918.
She received her bachelor’s degree from Ohio Wesleyan
Juliann Althoff, M.D.
22 Vital Signs Summer 2022 medicine.wright.edu 23You can also read
