Research News Tip Sheet: Story Ideas from Johns Hopkins Medicine

During the COVID-19 pandemic, Johns Hopkins Medicine Media Relations is focused on disseminating current, accurate and useful information to the public via the media. As part of that effort, we are distributing our “COVID-19 Tip Sheet: Story Ideas from Johns Hopkins” every other Tuesday.

We also want you to continue having access to the latest Johns Hopkins Medicine research achievements and clinical advances, so we are issuing a second tip sheet covering topics not related to COVID-19 or the SARS-CoV-2 virus. “Research News Tip Sheet: Story Ideas from Johns Hopkins Medicine” alternates Tuesdays with the COVID-19 Tip Sheet.

Stories in this tip sheet associated with journal publications provide a link to the paper. Interviews with the researchers featured may be arranged by contacting the media representatives listed.

SCIENTISTS LOOK TO CELL RECYCLING TOOLS FOR NEW WAYS TO TREAT PARKINSON’S DISEASE

Media Contact: Vanessa Wasta, M.B.A., [email protected]

Researchers at Johns Hopkins Medicine are taking a closer look at the molecular machinery that recycles mitochondria, the cell’s powerhouse, in efforts to ramp up the production of the energy-producing structures. Problems with mitochondria are a key aspect in the development of Parkinson’s disease.

In a study posted online Aug. 13, 2020, in the journal Stem Cell Reports, the researchers focused on brain cells called neurons which release a chemical messenger called dopamine. These so-called dopamine neurons have long been associated with processing behaviors involving reward and motivation, but they’ve also been implicated in regulating movement.

Tremors, muscle stiffness and other movement problems are common among people with Parkinson’s disease, which affects nearly 1 million people in the United States.

To study neurons associated with the disorder, scientific tools have recently been developed. These include fluorescent probes that can be easily used to identify newly developed and older mitochondria, says Ted Dawson, M.D., Ph.D., professor of neurology and director of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine.

Dopamine neurons, as well as other cells, maintain a quality control process that degrades old, worn-out mitochondria and makes new ones. Scientists have long known that malfunctioning mitochondria are found in dopamine neurons. In addition, a gene called PARKIN has been associated with a type of hereditary Parkinson’s disease that begins to appear in people younger than 40.

To better understand the gene’s behavior, Dawson’s team analyzed human dopamine neurons that lacked the PARKIN gene and were derived from both embryonic stem cells and people with Parkinson’s disease. These neurons lost their ability to make new, fully functional mitochondria.

The scientists noticed that the PARKIN-lacking neurons with malfunctioning mitochondria had more activation of a protein-making gene called PARIS which is linked to mitochondria regulation.

When Dawson and his colleagues genetically engineered the neurons to remove the PARIS and PARKIN genes — and thus their protein products — the neurons were still able to manufacture new mitochondria and continue — although to a lesser extent — to remove old mitochondria.

Cells with more PARIS activation lose the ability to make new mitochondria and neurons with less PARIS seem to make mitochondria easily, with some — but not total — effect on old mitochondrial removal. Dawson says this seems to indicate that the production of new mitochondria is critical to the maintenance and survival of dopamine neurons.

“Targeting PARIS with drugs to lower its protein levels may provide a new way to treat Parkinson’s disease,” says Dawson.

The value of patents owned by Valted LLC could be affected by the study described in this news item. Dawson is a founder of Valted LLC and holds an ownership equity interest in the company. This arrangement has been reviewed and approved by The Johns Hopkins University in accordance with its conflict of interest policies.

CLINICIANS USE ARTIFICIAL INTELLIGENCE TO DIAGNOSE EAR INFECTIONS MORE ACCURATELY

Media Contact: Danny Jacobs, [email protected]

A child pulling his or her ear in pain typically results in a parent scheduling a doctor’s appointment to check for a medical problem. However, studies have consistently shown that it’s a coin toss whether or not a pediatrician or a non-specialist can correctly diagnose an ear infection.

“The ears are just a nice and easy thing about which to say, ‘This is why my child isn’t sleeping,’” says James Clark, M.B., B.Ch., B.A.O., assistant professor of otolaryngology - head and neck surgery at the Johns Hopkins University School of Medicine. “It’s a problem looking for an explanation.”

Incorrect diagnoses can be frustrating and time-consuming for parents, not to mention the ear, nose and throat doctors called in for a second opinion. Clark and Therese  Canares, M.D., assistant professor in pediatric emergency medicine at the Johns Hopkins University School of Medicine, believe artificial intelligence (AI) could help better diagnose and manage ear infections, even remotely from a patient’s home. They are co-inventors of OtoPhoto, the world’s first smart otoscope, a device that takes images of the inner ear and uses machine learning to determine whether or not an infection exists.

OtoPhoto’s visuals are analyzed by a proprietary algorithm that makes the diagnosis. The images also can be shared with a specialist in real time during a telehealth appointment, an added benefit when many are avoiding office visits because of the enduring coronavirus pandemic.

“Even if there is an ear infection,” says Canares, “our hope is OtoPhoto enables them to get both the diagnosis and treatment at home, without getting exposed to COVID-19.”

OtoPhoto recently received $20,000 from the National Capital Consortium for Pediatric Device Innovation’s “Make Your Medical Device Pitch for Kids!” virtual competition. The development team also includes Mathias Unberath, Ph.D., an assistant professor in the Department of Computer Science at the Johns Hopkins Whiting School of Engineering; and John Rzasa, Ph.D., chief engineer at the Robert E. Fischell Institute for Biomedical Devices, within the A. James Clark School of Engineering at the University of Maryland, College Park.

The pitch award “validated that we were on to something, and that people outside our core team believe in us, too,” says Canares.

Along with developing a prototype thanks to a $300,000 grant from the Leon Lowenstein Foundation, the team has submitted a provisional patent application for its technology through Johns Hopkins Technology Ventures and is looking into forming a startup.

Canares and Clark have participated in Johns Hopkins’ I-Corps program, an immersive entrepreneurship learning experience developed by the National Science Foundation, as well as Hexcite, an early-stage medical software accelerator program hosted by the Johns Hopkins Medicine Technology Innovation Center.

Canares says the team hopes to have some very early efficacy data by the middle of 2021 as product development continues. Meanwhile, they have already started talking with parents of children with recurrent ear infections who are “head-over-heels for this idea,” she says.

“We’re starting to recognize that maybe there’s a need we can fill,” she says.

STUDY LOOKS TO PAST TO DEFINE NEED FOR FUTURE DIVERSITY AMONG INTERNAL MEDICINE PHYSICIANS

Media Contact: Michael E. Newman, [email protected]

According to U.S. Census Bureau and academic projections, the United States population will look much different in 2060 than it does today. Of the nearly 420 million Americans expected in 40 years, it’s likely that 60% will be racial and ethnic minorities while adults age 65 or older will make up 25%. Looking ahead, researchers at Johns Hopkins Medicine and the Association of American Medical Colleges (AAMC) recently asked if the workforce in internal medicine of that time will properly reflect the diverse country it will serve.

They looked at how diversified that workforce has become over the past four decades — to gain insight into what will be needed in the future — in a study posted online Sept. 1, 2020, in JAMA Network Open.

“The projected changes in the U.S. population of 2060 will lead to a larger, more diverse population, with increasingly complex medical care needs that will bear directly on the health and economy of future generations,” says study lead author S. Michelle Ogunwole, M.D., a fellow in the  Division of General Internal Medicine at the Johns Hopkins University School of Medicine and a 2020 Health Disparities Research Institute Scholar selected by the National Institute on Minority Health and Health Disparities. “A larger, more diverse physician workforce could help meet these needs and improve patient outcomes.”

For their study, the researchers used data from the Association of American Medical Colleges (AAMC) Faculty Roster and Applicant Matriculation File to capture full-time U.S. medical school faculty and matriculated students, and population data from the U.S. Census Bureau. The period examined was 1980 to 2018.

The researchers used this information to calculate the proportions of women and individuals from racial/ethnic groups who are underrepresented in medicine (URM) among internal medicine faculty and the faculty in all other clinical departments. These ratios were then compared with (1) the proportion of females and URM matriculants in U.S. medical schools and (2) the proportion of female and underrepresented minorities in the total population.

In 2018, the researchers report, women made up 40.3% of U.S. internal medicine faculty, but that is still lower than the women faculty in all other clinical departments (43.2%). During the study period, the percentage of URMs more than doubled but still makes up only a small percentage — 9.7% in 2018 — of all internal medicine physicians.

The researchers also state that the number of women among medical school matriculants grew steadily over the 38-year study span and now closely matches the U.S. female population percentage (50.7% to 50.8%). Although the percentage of URM matriculants has nearly doubled since 1980, the study shows it still lags far behind underrepresented minorities in the U.S. population (18.1% to 31.5%).

“Our findings show that progress has been made in diversifying academic internal medicine faculty; however, it still represents a low proportion of the discipline’s workforce and does not yet reflect the nation’s population,” says study senior author Sherita Golden, M.D., M.H.S., vice president and chief diversity officer for Johns Hopkins Medicine and professor of medicine at the Johns Hopkins University School of Medicine. “Continued efforts to increase this diversity could greatly improve the quality of medical education and, in turn, better meet the health care needs of a society that is rapidly diversifying itself.”

“This conversation is timely as we grapple with the racial disparities in COVID-19 outcomes and think about the complex chronic diseases that may have contributed to those disparities, as well as the ones that will persist long after this pandemic abates,” Ogunwole says.

MOTOR LEARNING PROCESSES INFLUENCE HOW HUMANS LEARN NEW BEHAVIORS

Media Contact: Waun’Shae Blount, [email protected]

Motor behaviors are part of all basic human activities, from talking and breathing to standing, walking and playing instruments or sports. These motor skills require that the nervous system first learns how to move by creating internal commands and then, with the commands in place, enable humans to repeat the movements thereafter. In a paper published in the July 25, 2020, issue of The Neuroscientist, a team of Johns Hopkins Medicine and University College London researchers explain the underlying bases behind such learning.

By reviewing previously completed behavioral and neurophysiological studies by Johns Hopkins Medicine and other sources that used two noninvasive brain stimulation techniques, the researchers evaluated data to better define the “big picture” about motor learning. This enabled a more comprehensive understanding of how humans learn new motor skills and which parts of their brain are involved. This information is critical to help design approaches to enhance learning or leverage it in the context of rehabilitation.

“In the long run, we hope to see if stimulating specific parts of the brain can increase motor function, especially in patients who are recovering from some form of brain injury,” says physiatrist-in-chief Pablo Celnik, M.D., director of both the Department of Physical Medicine and Rehabilitation and the Center of Excellence in Stroke Treatment, Recovery and Rehabilitation at the Johns Hopkins University School of Medicine.

Researchers in previous studies have used two noninvasive and painless brain stimulation techniques to asses patient motor learning and performance progress. The methods, known as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are designed to impact specific areas of the brain by delivering mild shocks through the patient’s skull. The stimulation allows for brief disruption of the function in those regions, enabling researchers to note any irregular behavior in the patient.

In the past, TMS has shown benefits for patients with depression for whom antidepressant medications provide no help or cannot be tolerated. Similarly, research also has demonstrated cognitive improvement in some patients undergoing tDCS, showing that the technique may be helpful in treating depression, anxiety, Parkinson’s disease and chronic pain. For patients with neurological diseases including spinal cord injuries, Alzheimer’s disease and stroke, brain stimulation techniques may aid in a patient’s recovery after a negative event. Through targeted rehabilitation techniques, such as TMS and tDCS, a patient’s motor learning abilities can be improved as he or she adapts to new movements while regaining function.

Motor learning involves many different processes to ensure smooth and accurate movements. These processes enable those abilities that are learned by different areas of the brain — such as playing competitive sports, performing a Beethoven symphony or rock climbing a mountain with bare hands.

“All of these functions interplay with each other in a very coordinated fashion,” says Celnik.

Looking at the big picture revealed by analyzing data from numerous TMS and tDCS studies performed in Celnik’s lab and others, the researchers identified the parts of the brain involved in the acquisition and retention of voluntary movements and motor skills. When tDCS was applied over specific brain regions that control some aspects of motor function, patients and healthy individuals showed increased excitement and better retention of their new motor memories.

Additionally, the authors reason that learning new skills involves different aspects of motor control with slightly different timings and roles during the overall learning process.

The researchers next plan to determine whether different learning processes can supplement each other during illness. If so, this would imply that when one area of the brain has a lesion, another part of the brain may be able to compensate. Such a finding would be significant because it could enable clinicians to develop better rehabilitation interventions that facilitate recovery after brain disease.

RACIAL/ETHNIC DISPARITIES IN CARE FOR PATIENTS WITH FAILING KIDNEYS UNCHANGED FOR DECADE

Media Contact: Michael E. Newman, [email protected]

It’s well known that when a patient with chronic kidney disease (CKD) begins heading toward eventual organ failure, appropriate, thorough, personalized and timely care from a nephrologist in the year prior to the start of dialysis for end-stage kidney disease (ESKD) is the key to more successful patient outcomes and often, survival itself. However, a new study by Johns Hopkins Medicine, the Johns Hopkins Bloomberg School of Public Health, the Harvard Medical School and the Duke University School of Medicine shows that racial and ethnic disparities in the availability and quality of this critical care that existed in 2005 did not improve in the decade that followed.

The findings from this study were reported online Aug. 27, 2020, in JAMA Network Open.

Using data from the U.S. Renal Data System — a national registry that collects, analyzes and distributes information about ESKD throughout the country — the researchers studied more than 1 million who began maintenance dialysis treatment between Jan. 1, 2005, and Dec. 31, 2015. Mathematical models were used to examine national trends in the nephrology care these patients received at least 12 months prior to the start of their dialysis treatments, primarily to identify and document disparities in this care linked to race or ethnicity based on patient outcomes.

Successful outcomes, as documented in previous studies, may include improved patient survival odds; reduced hospitalizations and complications; increased quality of life; better preparation for dialysis; and greater chance of receiving a kidney transplant.

The measure of disparity in this study was the adjusted odds ratio. An adjusted odds ratio defines the likelihood that an outcome will occur in response to a specific factor, once all other potential confounding variables have been removed (adjusted).

The 1,000,390 adults evaluated were 54% White, 28% Black, 14% Hispanic and 4% Asian. More than half (54%) were women. Overall, 31% of patients received at least 12 months of predialysis nephrology care.

As a result of their retrospective evaluation, the researchers found that compared with White adults between 2005 and 2007, the odds of receiving predialysis nephrology care was 18% lower for Black adults; 33% lower for Hispanic adults; and 16% lower for Asian adults. Between 2014 and 2015, similar disparities were observed: 24% lower for Black adults; 39% lower for Hispanic adults; and 10% lower for Asian adults.

“Our findings suggest that national strategies are desperately needed to address the continuing — and life-threatening — racial and ethnic disparities in predialysis nephrology care,” says study lead author Tanjala Purnell, Ph.D., M.P.H., an associate director of both the Johns Hopkins Urban Health Institute and the Johns Hopkins Center for Health Equity, as well as assistant professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health with a joint faculty appointment in the Department of Surgery at the Johns Hopkins University School of Medicine.