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Research news tip sheet: Story ideas from Johns Hopkins Medicine

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NO BONES ABOUT IT: WILD GORILLAS DON'T DEVELOP OSTEOPOROSIS LIKE THEIR HUMAN COUSINS

Media Contact: Rachel Butch, rbutch1@jhmi.edu

In a study of gorilla skeletons collected in the wild, Johns Hopkins Medicine researchers and their international collaborators report that aging female gorillas do not experience the accelerated bone loss associated with the bone-weakening condition called osteoporosis, as their human counterparts often do. The findings, they say, could offer clues as to how humans evolved with age-related diseases.

The study was published on Sept. 21, 2020, in Philosophical Translations of the Royal Society B.

"Osteoporosis in humans is a really interesting mechanical problem," says Christopher Ruff, Ph.D., professor at the Center for Functional Anatomy and Evolution at the Johns Hopkins University School of Medicine. "In terms of natural selection, there is no evolutionary advantage in developing bone loss with aging to the point of a potential fracture. By looking at close relatives of humans on the evolutionary tree, we can infer more about the origins of this condition."

The Johns Hopkins research team worked with the Rwanda Development Board, Gorilla Doctors, the Dian Fossey Gorilla Fund International and George Washington University researchers to study the bone collection of mountain gorillas from Rwanda's Volcanoes National Park. The park is one of the few places in the world where conservationists can observe wild gorillas throughout their lifetimes. After a gorilla dies in the wild, its bones are carefully gathered, cataloged and added to the collection housed at the Fossey Fund's Karisoke Research Center.

"This detailed, long-term data on individual gorillas is critically important to this kind of anatomical research work," says Ruff. "Extensive demographic information, including the age at death, allows investigations that are difficult or impossible to carry out in other wild primate populations."

Ruff and his colleagues were able to analyze the bones of 34 wild mountain gorillas -- 16 females and 17 males, ages 11 to 43 years. This spans the full adult range of the species. Using a specialized CT scanner brought to Rwanda, the researchers examined the leg, arm and spine bones from each animal (including the femur, tibia, radius, ulna, humerus and lumbar vertebrae), taking measurements of bone density and geometry.

The researchers found some features of skeletal aging among the gorillas that are similar to those observed in humans, including a general widening of the diameter of long bones and thinning of the bone wall. However, the gorilla bones did not show any of the accelerated bone mineral loss associated with age-related osteoporosis in human skeletons. In humans, women tend to lose bone mineral density more than men. However, in the mountain gorillas, there was no significant difference in bone density or overall strength between older males and females.

These differences, Ruff says, may be explained by the fact that gorillas continue to have offspring throughout their lives, maintaining hormonal levels that help protect them from bone loss. Higher activity levels also may help grow and then maintain stronger bones.

Based on their study results, Ruff and his colleagues hypothesize that this new life stage in humans emerged after the evolutionary split between humans and African apes, and that it could be when some of our age-related diseases, including osteoporosis, originated.

HPV HOME TEST MAY REDUCE CERVICAL CANCER DISPARITY, IMPROVE OUTCOMES FOR BLACKS, LATINOS

Media Contact: Danny Jacobs, djacob41@jhmi.edu

David Sidransky, M.D., calls the Pap smear one of the "greatest successes" in cancer screening.

"Every woman in the United States is supposed to be going for a regular Pap smear exam, and if they do, the chance of developing cervical cancer is very low," says Sidransky, an expert in the molecular genetic detection of cancer and director of head and neck cancer research in the Department of Otolaryngology-Head and Neck Surgery at the Johns Hopkins University School of Medicine.

Despite the Pap smear's effectiveness, however, there are geographic and racial disparities regarding who takes the test and what is an appropriate follow-up. Studies have shown that older women who did not receive the vaccine for the human papilloma virus (HPV, a known cause of cervical cancer) have a higher risk for developing cervical cancer, while Black women have a higher incidence of the disease and do more poorly after diagnosis. Moreover, in many Latino communities, the test isn't widely accepted.

That's why Sidransky has been working with former Johns Hopkins Medicine researcher Rafael Guerrero-Preston, Dr.P.H., M.P.H., on another way to identify women at greatest threat from cervical cancer -- a home test they can do themselves. The self-administered screening tool can accurately identify a higher risk for future cervical cancer by finding methylated DNA segments.

Higher levels of methylation -- the addition of a methyl group (three hydrogen atoms bound to a carbon atom) to a DNA molecule -- are associated with a greater likelihood that cervical cells will progress to a cancerous state.

"If someone tests positive and the early steps of cancer development are detected, we can treat it before it becomes invasive," says Sidransky.

The new test involves a robust molecular process in which cells taken from a vaginal swab are used to detect both HPV and methylated DNA. While a Pap smear only analyzes a small sample of cells from a single spot on the cervix, Sidransky says the home test checks both the swab site and the surrounding region for cervical cancer's early warning signals.

"Even if you miss the presence of a tumor, sampling the larger area enables you to diagnose a problem and better estimate the likelihood that it will progress to cancer," he says.

Sidransky envisions that a woman could swab herself, mail the sample and get results back in less than two weeks, similar to the process for home colon cancer screening kits already in use.

"I think for us to succeed, ultimately the test must be able to be done in any lab," he says. "The goal of this is to make this as low-cost and distributable as possible, including to lower income countries worldwide."

The methylation test was licensed through Johns Hopkins Technology Ventures to LifeGene BioMarks, a Johns Hopkins spinoff company. Guerrero-Preston, the firm's founder and chief scientific officer, worked in Sidranksy's lab for a decade.

LifeGene BioMarks and Sidransky recently received two grants totaling more than $1.5 million through the U.S. Small Business Administration's Small Business Innovation Research program. The grant funds will be used to first make the test more robust for improved cell sampling and then to enable clinicians to examine a larger number of samples for clinical validation.

"I think there is an excitement in terms of what this test could bring in advancing self-screening for cervical cancer and in bridging the disparity gaps that currently keep quality screening from all women," Sidransky says.

STUDY FINDS OBESITY MEDICINE SPECIALISTS ARE USING EVIDENCE-BASED CARE

Media Contact: Michel Morris, melben1@jhmi.edu

The United States obesity rate is now more than 40%, and physicians are looking for new and more effective ways to treat the problem. In 2013, the American Medical Association recognized obesity as a complex, chronic disease that requires medical attention. However, past research studies showed that the percentage of physicians providing adequate counseling and treatment to patients with obesity remains low.

Additionally, patients with obesity are often unaware that such services even exist.

To better understand the state of obesity medicine in the United States, Johns Hopkins Medicine researchers surveyed physicians certified in the discipline by the American Board of Obesity Medicine (ABOM) found that these practitioners, whose numbers are low, commonly offer key services supported by scientific research and clinical trials.

This suggests that primary care clinicians can be increasingly confident that their patients will receive this "evidence-based care" when referred to an obesity specialist. Overall, most of the respondents endorsed the use of nutrition, behavioral services, weight-loss surgical care and anti-obesity medications approved by the U.S. Food and Drug Administration (FDA).

The findings were published online on Sept. 10, 2020, in the journal Clinical Obesity.

"Modifications are key to losing weight," says study lead author Kimberly Gudzune, M.D., M.P.H., associate professor of medicine at the Johns Hopkins University School of Medicine, and director of both the Johns Hopkins Healthful Eating, Activity and Weight Program and the Johns Hopkins Obesity Medicine Fellowship. "A lot of physician training doesn't include obesity treatments such as lifestyle counseling and medication management, and without it, you're unlikely to help patients lose weight. We want to ensure that obesity medicine providers are providing great care to help patients achieve long-term success."

Through ABOM, Gudzune surveyed over 490-obesity medicine certified physicians. The physicians were asked about their current clinical practices in the hope of learning if the services they offer are in line with currently accepted science.

Gudzune and her colleagues found that the majority of ABOM physicians responding to their survey offered nutritional (90%), exercise (68%) and mental health (77%) counseling to their patients. Only a few offered minimally invasive procedures (24%), but most provided care before and after surgery (63%). Most (83%) prescribed FDA?approved medications -- both short? and long?term agents (71%).

Gudzune's team concluded that most of the survey participants' obesity medicine services are evidenced based.

Gudzune plans to use the study's findings to raise patient awareness that there are health care providers specifically trained to help with obesity and its consequences, such as a greater risk of cardiovascular disease, diabetes, certain cancers and premature death. She also hopes the study results can be used to identify where gaps may exist in obesity care and to support development of more comprehensive treatments.

TEMPERATURE-SENSITIVE, LONGER-LASTING EYEDROPS MAY MEAN LESS APPLICATIONS, BETTER THERAPY

Media Contact: Rachel Butch, rbutch1@jhmi.edu

Johns Hopkins Medicine researchers have created a gel-based eyedrop that responds to the eye's temperature and allows drugs to remain longer on the eye surface, penetrating tissues more effectively without obscuring vision. Tested in mice, rabbits and pigs, the formulation could reduce the number of times a day that patients need to reach for the eye dropper.

The study was published Sept. 7, 2020, in Nature Biomedical Engineering.

"The main problem with conventional liquid eye drops is that they are very short lasting and not very much drug gets into the eye because the watery substance is blinked away quickly," says Laura Ensign, Ph.D., associate professor of ophthalmology at the Johns Hopkins Wilmer Eye Institute. "So, eye drops often have to be applied multiple times per day to be effective."

More than 90% of drugs for eye conditions are delivered by liquid eyedrops, say the researchers. For people with irritation, glaucoma or dry eye, drops are required multiple times per day. Each dose comes with a small risk of side effects, which can cause patients to skip doses and reduce the treatment's effectiveness. Patients who do so risk additional problems such as prolonged discomfort and vision loss.

In the study, the team of biomedical engineers and ophthalmologists used a compound, called Pluronic F127, a polymer that responds to body temperature and creates a gel. Currently, Pluronic F127 is a component in various over-the-counter lubricating eye drops, but at very low concentrations. These formulations do not become a gel on contact with the eye. Previous tests in animals of a gel-forming concentration often resulted in clumpy, uneven layers on the eye that quickly got caught up in the lids and lashes. Vision also was obscured.

To solve the clumping problem, the researchers needed to create a drop with enough Pluronic F127 molecules to form a gel, but fluid enough to spread across the eye. They landed on an ionic carrier solution that could be absorbed into cells on the eye's surface, leaving behind the Pluronic F127 polymers. The solution keeps the gelling molecules apart long enough for them to spread out and bind together in a uniform layer.

"It's a simple modification as far as composition, but it causes the drops to behave very differently when applied," says Ensign.

In tests on rabbits, the drops were administered five times each day for two weeks without any adverse effects seen in the rabbits' behavior (such as increased blink rate or eye rubbing) or on eye tissues examined under a microscope. Tests on pigs, whose eyes are more like human eyes in size and composition, showed similar results.

The researchers were surprised to see that since the gel-based drops remained on the eye longer than liquid drops, the treatments could reach the eye's notoriously hard to penetrate back layers. Tissues in these layers -- such as the retina, choroid and macula -- are sites for some of the most common blinding diseases, including diabetic retinopathy and macular degeneration.

In pigs induced by a laser to develop symptoms similar to human macular degeneration, the researchers applied a daily dose of their new eye drops carrying a drug called sunitinib that slows the disease's progression. This cut in half the amount of vision-blocking blood vessel overgrowth in the retina when compared with pigs receiving drops without the drug.

The researchers caution that while promising, more tests are needed before the drops can be tested in humans. They intend to create a company to explore further applications for the drops, including their use with other medications.

Ensign and Hanes are working with Johns Hopkins Technology Ventures to form a startup to license the technology.

BALANCING OLDER PATIENTS' RISK REDUCTION WITH AUTONOMY AND RESPECT

Media Contact: Michel Morris, melben1@jhmi.edu

Many people will become caregivers informally at some point, and geriatrician Mattan Schuchman, M.D., hopes to start a discussion -- among them, the love ones for whom they care and the doctors who work with them -- about the considerations that should be made. When an older patient's safety and independence are in conflict, Schuchman encourages clinicians to weigh several factors: the patient's perspective, the perspectives of other major stakeholders, clinician biases, liability, and the magnitude of the patient's risk and risk to others.

Schuchman and his colleagues discuss these considerations in a commentary in the September 2020 issue of Medical Clinics of North America.

"We should consider both a person's autonomy and ability to make their own choices, and try to balance that with concerns for the person's safety and well-being. It may not always be concordant," says Schuchman, medical director of Johns Hopkins Home-based Medicine and an assistant professor of medicine at the Johns Hopkins University School of Medicine.

Schuchman says these challenges commonly arise in decisions about living environment and driving. From physical rehabilitation to installing home modifications to changing the residence (with a change in the level of care), many decisions about health care for vulnerable adults focus on safety.

In some situations, Schuchman says, clinicians' ethical obligations to promote health and prevent harm may be at odds with their desire to respect the patient's determination to be self-sufficient.

Finding the right answer is not the goal, Schuchman says. He wants clinicians to find fair, transparent ways to choose among morally acceptable alternatives. He hopes patients and their providers can fashion agreements that optimize both safety and independence.

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