Research News Tip Sheet: Story Ideas From Johns Hopkins

Newswise — 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 Tuesday throughout the duration of the outbreak.

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 every Thursday, covering topics not related to COVID-19 or the SARS-CoV-2 virus.

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

STUDY PROVIDES EVIDENCE OF PREMATURE AGING IN OLDER ADULTS

WITH HIV

Media Contact: Waun’Shae Blount

In recent years, a variety of treatments have enabled people with the human immunodeficiency virus (HIV) to live long, healthy lives. However, with advanced age comes the increased risk of developing cognitive impairment, so it’s vitally important to better define the specific factors behind cognitive decline in people living with HIV to treat this group in the earliest stages. Until recently, such understanding has been difficult to obtain, as the underlying reasons for loss of memory, thinking impairment and other cognitive deterioration among older individuals with HIV seem to overlap with those seen in seniors who do not have the virus.

In a study published in the April 8, 2020, issue of Journal of NeuroVirology, Johns Hopkins Medicine researchers used positive emission tomography, or PET, scans to determine if cognitive decline in older individuals with HIV was related only to the presence of the virus or whether it might be connected to a commonly seen factor in cases of Alzheimer’s disease and other forms of dementia: the accumulation of a protein fragment called beta-amyloid, a sticky compound that disrupts communication between nerve cells in the brain and eventually kills them.

The researchers studied 73 Maryland residents age 50 and older (48 HIV-positive and 25 HIV-negative). Participants went through an extensive evaluation process, including a physical exam, HIV status check, neuropsychological assessment, magnetic resonance imaging (MRI) of the brain, and a spinal tap to analyze fluid surrounding the brain for beta-amyloid protein. Finally, participants were injected with a radiotracer that binds with beta-amyloid in the brain, so that a PET scan could determine the levels of the protein accumulated there.

Among individuals with HIV, increasing cognitive decline was associated with increasing depression and decreasing intelligence (as defined by IQ scores). These people showed greater amyloid protein buildup in the centrum semiovale, a structure within the white matter deep in the brain, compared with individuals without HIV. Loss of function in the centrum semiovale is believed to be a factor in impairments of attention, intelligence and academic achievement.

Along with accumulations in the centrum semiovale, individuals in their 50s with HIV also exhibited greater amounts of amyloid protein in other white matter regions associated with executive function and memory, in contrast to individuals without HIV.

“These findings provide evidence for premature aging in individuals with HIV,” says James Brasic, A.M., M.A., M.D., M.P.H., M.S., assistant professor of radiology and radiological science at the Johns Hopkins University School of Medicine and a member of the research team. “Our future studies will focus on investigating therapies to slow or eliminate cognitive impairment in older people with HIV, including clinical trials and extensive imaging to evaluate the impact of those interventions.”

REMOTE COACHING CAN HELP BREAST CANCER SURVIVORS ACHIEVE HEALTHY WEIGHT LOSS

Media Contact: Valerie Mehl

A telephone coaching and web-based weight loss plan, referred to by scientists as the “POWER-remote intervention,” helped half of overweight and obese breast cancer survivors lose 5% or more of their body weight after six months — and keep it off for 12 months, according to a recent study led by Johns Hopkins Kimmel Comprehensive Cancer Center researchers.

Published in the April 10, 2020, issue of the journal Clinical Cancer Research, the study enrolled 87 women with minimally to moderately invasive breast cancers and a body mass index of 25 or higher (a BMI of 25 to 29 is considered overweight; 30 or more is obese). All participants had completed surgery and any prescribed radiation and chemotherapy. A diverse group of patients ages 30 to 73, including 20% African-American women, was randomly divided into two sections, with 45 women completing the POWER-remote intervention and 42 completing a self-directed weight loss plan.

Women participating in the POWER-remote intervention received telephone-based behavioral weight loss coaching — weekly for the first three months, then monthly through the end of the yearlong study — along with access to a web-based platform to monitor their diet, exercise and weight. Women in the self-directed weight loss group received one coaching session at the start of the study, along with standard diet and exercise guidelines provided by the National Heart, Lung and Blood Institute.

After six months, 51% of women assigned to the POWER-remote intervention lost 5% or more of their body weight, compared with 12% of those who participated in a self-directed weight loss program. Twelve months after the start of the study, 51% of those in POWER-remote group maintained their weight loss, compared with 17% of those in the self-directed group. The average weight loss in the remote coaching group after six and 12 months was 4.6 kilograms (10.1 pounds), compared with 0.5 kilograms (1.1 pounds) at six months and 0.4 kilograms (.9 pounds) at 12 months among the self-directed group.

Women receiving the POWER-remote intervention in the trial had almost a 50% decrease in leptin, whereas the self-control group essentially had unchanged levels. Leptin, a hormone released primarily by fat cells, and a biomarker for weight gain, has been shown to increase breast cancer cell proliferation, invasion and migration.

“The results of our study showed that the POWER-remote coaching is a feasible and effective weight loss intervention for breast cancer survivors,” says Kimmel Comprehensive Cancer Center investigator and assistant professor of oncology Cesar A. Santa-Maria, M.D., M.S.C.I.

MOUSE STUDIES SUGGEST INNATE LYMPHOID CELL MAY BE KEY FACTOR IN AUTOIMMUNE ATTACKS ON HUMAN HEARTS

Media Contact: Michael E. Newman

Innate lymphoid cells, or ILCs, are components of the immune system that produce cytokines, protein molecules that act as signals to help direct and regulate the body’s immune response against foreign invaders. In a recent study using mice, researchers at the Johns Hopkins University School of Medicine and the Czech Republic’s Institute for Clinical and Experimental Medicine (IKEM) demonstrated that one type of ILC can sometime switch roles, becoming an immunity villain instead of a hero by provoking the development of eosinophilic pericarditis, a rare and potentially deadly inflammation of the heart muscle.

There are three types of ILCs defined by the type of cytokines they produce. Group 2 ILCs, also known as ILC2s, are found in many organs throughout the body. They are most prevalent in the fluid filling the pericardium, the double-walled sac containing the heart and the roots of the vessels entering and exiting the heart.

“We suspected that ILC2s might be connected to the development of eosinophilic pericarditis, so we decided to try to confirm that link and, if so, then look for the mechanism behind it,” says Daniela Cihakova, M.D., Ph.D., associate professor of pathology at the Johns Hopkins University School of Medicine and the senior author of the paper discussing this research published March 3, 2020, in the journal Cell Reports.

In a 2012 study — led by former Johns Hopkins Medicine researcher DeLisa Fairweather, Ph.D. (now with the Mayo Clinic), in collaboration with Cihakova and others — the researchers found that if they injected interleukin-33 (IL-33) — a cytokine produced by the spindle-shaped cardiac cells known as fibroblasts — into the pericardium cavity of mice, it led to a massive accumulation of eosinophils, white blood cells that in proper numbers will neutralize parasites, viruses and certain types of fungi that attack the heart. However, too many eosinophils on the job can result in a misdirected attack on healthy heart muscle cells. This causes eosinophilic pericarditis.

The researchers theorized that innate lymphoid cells might play a key role in the autoimmune heart disease process.

To test their hypothesis, the researchers conducted a set of experiments in mice. First, they injected IL-33 into three mouse types: wild type (normal), with T and B cells — the primary immune system fighters — and ILC2s; genetically bred to only have ILC2s; and genetically bred without any of the three. Only the mice lacking ILC2s did not get pericarditis, indicating it was the pivotal factor. To confirm the finding, ILC2s were injected into the third type of mice that did not have them naturally. They showed accumulations of eosinophils and damage to the pericardium as well.

A third mouse experiment revealed the pathway by which ILC2s lead to pericarditis. Knowing that ILC2s release two cytokines, interleukin-5 (IL-5) and interleukin-13 (IL-13), in response to IL-33, the researchers showed that when this occurs, cardiac fibroblasts are stimulated to produce a chemical called eotaxin, which attracts eosinophils. Concurrently, the fibroblasts produce more IL-33, which in turn, pushes the ILC2s to produce more IL-5 and IL-13 — a feedback loop that intensifies the eosinophil accumulation and its destructive autoimmune response.

Another investigation determined that the eosinophils could traffic to the heart not only through the bloodstream, but also from the mediastinal cavity — the space around the heart.

Finally, study collaborators led by Vojtech Melenovsky, M.D., Ph.D., at IKEM obtained pericardial fluid from human patients with different cardiac diseases. The Cihakova team examined the samples and found large numbers of ILC2s exclusively in the two patients being treated for pericarditis. This, Cihakova says, makes it highly likely that the disease in humans follows the same pathway she and her colleagues observed in mice.

WAGE BONUSES MOTIVATE SOBRIETY AND EMPLOYMENT AMONG PEOPLE RECOVERING FROM ADDICTION

Media Contact: Vanessa McMains, Ph.D.

Poverty is an independent risk factor for drug abuse that addiction treatment plans largely ignore. Experts believe that a gold-standard drug treatment intervention would be one that could promote employment, reduce drug use and help those ravaged by the opioid crisis to better integrate back into their communities, while addressing underlying poverty.

Now, Johns Hopkins Medicine researchers have tested a new wage bonus plan for treating people with opioid dependence. In a study published in the Feb. 21, 2020, issue of the Journal of Epidemiology & Community Health, the researchers report that adding $8 an hour to a paycheck may help those in recovery stay drug free longer, as well as encourage them to get and hold regular jobs.

During the yearlong intervention, 65% of people with wage supplements provided urine samples free of opioids and cocaine, compared to 45% of those without wage supplements. People with wage supplements were also 2.9 times more likely to get a job and 2.7 times more likely to rise out of poverty by the end of the year than those without the bonuses.

“We were hoping to have a positive result from our study, but I don’t think we expected it to work quite so well,” says August Holtyn, Ph.D., assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “The vast majority of unemployed people that participated entered into the workforce with minimum wage positions, so we think the wage supplement is helpful in providing motivation to keep jobs that at times can be stressful and difficult.”

She says participants worked in construction, grocery stores, the food service industry, house cleaning and delivery.

Although the wage supplements and drug testing stopped after the study period, the researchers plan to follow participants for another year to see if the reduced drug use and consistent employment effects persist. They also are testing their wage supplement intervention with homeless adults who have alcohol use disorder.