Brown University

Scientists find RNA with special role in nerve healing process

The discovery in lab mice that an “anti-sense” RNA is expressed after nerve injury to regulate the repair of damage to the nerve’s myelin coating could lead to a treatment that improves healing in people.

PROVIDENCE, R.I. [Brown University] — Scientists may have identified a new opening to intervene in the process of healing peripheral nerve damage with the discovery that an “anti-sense” RNA (AS-RNA) is expressed when nerves are injured. Their experiments in mice show that the AS-RNA helps to regulate how damaged nerves rebuild their coating of myelin, which, like the cladding around a cable or wire, is crucial for making nerves efficient conductors.

Nikos Tapinos, associate professor of neurosurgery in the Warren Alpert Medical School of Brown University and senior author of the study in Cell Reports, said his team was able to control expression of the AS-RNA in the lab and therefore the transcription factor Egr2 that prompts myelin-building Schwann cells into action.

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What to expect: the FDA’s plan to limit nicotine in cigarettes

PROVIDENCE, R.I. [Brown University] — When the U.S. Food and Drug Administrationannounced on July 28 a new push to substantially reduce and limit the amount of nicotine in cigarettes, the policy was informed by an evidence base developed with critical contributions from Brown University’s Center for Alcohol and Addiction Studies (CAAS) in the School of Public Health.

For years, a group of faculty members, postdoctoral researchers and students has been studying many dimensions of nicotine reduction, including the impact such a policy might have on smoking behavior in general and on specific populations of smokers, some of whom might face unintended consequences. Among those researchers is Jennifer Tidey, a professor of psychiatry and human behavior and of behavioral and social sciences, who co-authored a particularly influential paper in the New England Journal of Medicine in 2015.

In the wake of the news out of Washington, we asked Tidey to share thoughts on Brown’s nicotine-reduction research and its impact on the FDA’s new initiative.

Q: What can your 2015 study tell us about the FDA’s plan to lower nicotine levels in cigarettes?

This study was designed to model the potential effects — positive and negative — of a nicotine-reduction policy for cigarettes. More than 800 smokers at 10 sites across the country were randomly assigned to receive either their usual cigarette brand or research cigarettes with varying levels of nicotine for a six-week period. The nicotine content of the research cigarettes ranged from a level similar to commercial cigarettes down to having less than 5 percent of the nicotine content of a commercial cigarette.

After six weeks, participants who had received the very low nicotine cigarettes smoked fewer cigarettes per day, were less dependent, had less cigarette craving and had minimal withdrawal discomfort. Even though none of the participants was trying to quit at study outset, those who had used very low nicotine cigarettes were more likely to try to quit when the study ended. The study supports the idea that this policy could be an effective regulatory method of reducing tobacco dependence in the U.S., making it easier for people to quit if they want to.

Q: How else has recent research at Brown contributed to the evidence base for this policy? 

Rachel Denlinger-Apte, a doctoral student in the School of Public Health, is an investigator in a study with more than 1,200 smokers that has been comparing the effectiveness of reducing the nicotine content of cigarettes immediately or gradually over a number of months. That study was recently completed and results should be available soon. And along with our co-investigators from the 2015 study, we have been looking at other measures collected in that study to see, for example, how acceptable people find these cigarettes, how supportive they are of a nicotine-reduction policy, and whether nicotine reduction has deleterious effects on weight gain, alcohol use, cannabis use or depressive symptoms.

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With lessons from the Holocaust, medical students consider health care ethics

PROVIDENCE, R.I. [Brown University] — By the time the students arrived at Auschwitz-Birkenau, they were prepared — they had read texts about the Holocaust, spoken with a survivor, viewed Berlin’s memorials and toured the halls where the Nazi regime planned its “euthanasia” and Final Solution campaigns to murder millions. But for Hyunwoo June Choo and Alexa Kanbergs, standing on the grounds of the Nazi killing center transformed merely knowing of these historical events into feeling them, vividly and palpably.

Monday, June 26, was a lovely summer day in Poland, Kanbergs recalled. She was struck by how the buildings of Birkenau, where Nazis gassed as many as 6,000 Jews a day to death, stood in juxtaposition with the beautiful surrounding landscape and the ubiquitous sounds of chirping birds.

“I viscerally felt something when I went to that site,” said Kanbergs, a third-year Warren Alpert Medical School student from Portland, Ore. “We had been reading about it, but you are removed from it because you are just learning about it. Then when you actually visit, it makes it a lot more real.”

Choo, a fourth-year medical school student from Los Angeles, was similarly struck. Organizers of the two-week program that had brought them to Germany and then Poland, the Fellowships at Auschwitz for the Study of Professional Ethics, had told them that “place has power.” In a huge camp built for the sole purpose of genocide, the meaning was clear.

“The entire week, we had been building up to this point,” Choo said. “We went to where the leaders had planned and strategized how to exterminate large masses of people. When I was actually there, I was just standing aghast at the expanse and the sheer vastness of this institution. Everything was deliberate. Everything was calculated.”

The Fellowships at Auschwitz program teaches medical, legal, business, journalism and divinity students to consider the ethics of their future professions in the context of the Holocaust’s catastrophic moral failings. Choo and Kanbergs had applied to the competitive fellowships out of a desire to transcend and therefore contemplate the day-to-day experience of their medical training.

“In medical school as students, we’re sort of thrown into wards and hospital systems and we see things — a lot of injustices play out on individual bodies,” Choo said. “We don’t really have the time or space to think through the systems behind a lot of the social circumstances that bring a patient in front of us. What this program allowed us to do was to think about ethics not as this lofty, abstract idea, but as something grounded in history.”

The point is not that inequities and injustices in the U.S. health care system have equivalence with the Nazi regime’s meticulously planned policies of mass murder, Kanbergs said. Instead, the point is to learn how to recognize and sustain clear moral vigilance in systems that produce injustice, regardless of its scale or whether it was intended.

“I don’t ever want to take away from the events that happened in the Holocaust and say that this is the same situation,”  Kanbergs said, “but I think about prisoners a lot, and I think about how we incarcerate individuals of color. I see these parallels with how we strip the rights of individuals and target certain classes of individuals. As physicians, we are put into these systems that allow for that to happen.”

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NaloxBoxes put lifesaving overdose drugs within ready reach

PROVIDENCE, R.I. [Brown University] — On the night of Saturday, June 3, just six days before Amos House installed six “NaloxBoxes” — wall-mounted kits with doses of the opioid overdose reversing medicine naloxone — a resident nearly died of an overdose.

In that case, the affected woman, who was found on the floor of a bathroom, survived because fellow residents happened to have their own naloxone and were ready to act, said Eileen Hayes, director of the homelessness and recovery services center on Pine Street in Providence. But now there are NaloxBoxes arrayed strategically around the center’s main building and residences so that the medicine will always be within reach to residents and staff alike.

“It’s crucial that we educate people and make it available,” Hayes said. “We’re a recovery program, and we’re working with men and women who are really working hard to be in recovery, and yet that doesn’t mean that relapse doesn’t happen.”

NaloxBoxes are the creation of professors Dr. Geoff Capraro of the Warren Alpert Medical School of Brown University and Claudia Rébola of the Rhode Island School of Design. Capraro, a Lifespan emergency medicine physician, had the idea that naloxone should be made readily available in public places where overdoses may occur. Through a connection he made at Brown Hack Health, he brought the idea to RISD, where Rébola has ultimately led the boxes’ design.

What they’ve developed is an emergency kit with the same goals as a fire extinguisher or an automated external defibrillator — to enable anyone in the wrong place at the right time to save lives. Nationally, drug overdoses are rising sharply, mostly because of opioids like heroin or prescription painkillers. The epidemic is especially severe in Rhode Island, where 336 people died from overdoses in 2016 alone, prompting a series of programs and actions by the governor including an executive order signed just today.

“There’s no publicly available naloxone,” Capraro said. “It’s all by prescription or pharmacy dispensed. So we saw potential for putting this medicine in the hands of bystander good Samaritans so they could give it quickly. The time to deliver the medicine matters.”

With grant support from the Rhode Island Department of Health and the Preventing Overdose and Naloxone Intervention program at the Miriam Hospital, Capraro and Rébola produced 48 boxes this spring. They have begun to install them this summer, conducting trainings in opiate overdose recognition and rescue in conjunction with the installations, beginning at Amos House and continuing at least 12 other community facilities such as shelters within the Rhode Island Coalition for the Homeless.

Simple and smart

The boxes, not much bigger than a ream of office paper, contain four injectable doses of naloxone, printed instructions for how to administer it and a mask for providing rescue breaths (in an overdose, people stop breathing). The boxes are also being outfitted with cellular electronics that send a simple text message to their host when they are opened. That way, whoever is responsible for the box is alerted when someone has used it, so that the possible emergency is documented and any taken naloxone can be refilled.

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