A Snapshot of Science: Detection of Alzheimer’s Disease, Development of Type 1 Diabetes, and Much More

We wanted to share some recent Mass General research that has been published in high impact, top-tier journals. This is just a small snapshot of the incredible research that takes place at Mass General each day — there’s lots more to find at massgeneral.org/research/news!

 

DETECTING AND TREATING STIFF TUMORS
Published in Nature Scientific Reports on August 14, 2017
(Summary submitted by Peter Caravan, PhD, of the Martinos Center for Biomedical Imaging)

In tumors, cancer cells are surrounded by a collection of proteins, enzymes, sugars, lipids, and minerals called the extracellular matrix (ECM). Many cancers have a fibrotic ECM, making the tumor stiff and preventing delivery of anti-cancer drugs. The presence of a fibrotic ECM is often associated with poor prognosis. We developed a new MRI method to detect tumor fibrosis non-invasively, and studied its effect in a mouse model of pancreatic cancer. The potential impact of this work is a new tool to stage the aggressiveness of tumors, guide treatment planning, and monitor the effectiveness of new tumor ECM altering treatments.

 

IMPACT OF BLOOD AND URINE FILTRATION IN LEAKY KIDNEY FILTERS
Published in Scientific Reports on August 16, 2017
(Summary submitted by Hua A. Jenny Lu, MD, PhD, of the Nephrology Division)

One major function of the kidney is filtering blood through an intricate “glomerular filter”. Disruption of any components of this highly sophisticated and dynamic filter’s structure leads to proteinuria (protein in the urine), a condition frequently seen in diabetic nephropathy and many other glomerular diseases. How blood filters though the glomerular filter and how proteinuria develops when the filter becomes leaky has not been well understood. This paper reports the application of a novel and powerful scanning microscopy technology, the Helium Ion microscopy (HIM) to identify previously unrecognized ultrastructural abnormalities of proteinuric glomerulopathy in animals. These newly discovered abnormalities provide important insight into the molecular and cellular mechanism underlying proteinuria kidney diseases.

 

OBSERVING THE DEVELOPMENT OF TYPE 1 DIABETES
Published in PNAS on August 24, 2017
(Summary submitted by Ralph Weissleder, MD, PhD, Director of the Center for Systems Biology)

Type 1 diabetes (T1D) is an autoimmune disease where insulin-producing cells are destroyed. Inflammation in islets of human patients has been hard to evaluate, given the challenging access to material. Now, our research team has discovered how the different cellular players interact. We created new reporter mice and new imaging agents where cells of interest (lymphocytes, macrophages, dendritic cells, beta cells) are fluorescent and can be observed by imaging. We were able to observe the intricate “dance” of different immune cells interacting with each other as diabetes develops. Throughout the process, Tregs (a unique type of T-lymphocyte) control the activation of many cell types. The “dynamic geography” of events uncovered here provide important clues to immunoregulation that underlies diabetes development.

 

NON-INVASIVE MEASUREMENT OF BRAIN ACTIVITY AND MEMORY ENCODING
Published in Scientific Reports on August 25, 2017
(Summary submitted by Meryem Yucel, PhD, of the Martinos Center for Biomedical Imaging)

Alzheimer’s disease (AD) is the most frequent cause of severe memory loss in the elderly. Early detection of AD is the key to preventing, slowing or stopping the disease. Near-infrared spectroscopy (NIRS) is a non-invasive neuroimaging technique capable of monitoring brain activation. Here, we investigated the utility of fNIRS in measuring the brain activity of healthy adults during memory encoding and retrieval under a face-name paired-associate learning task. Their study demonstrates that fNIRS can robustly measure memory encoding and retrieval-related brain activity. Future work will include similar measurements in populations with progressing memory deficits. Their approach, if successful, will introduce a non-invasive, inexpensive and easily accessible tool for identifying early stages of AD.

Hackathon Revolutionizes Care with Plan to Reduce Deadly Opiate Overdoses

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Members of We Are Allies, from left, Jessica Moreno, PharmD, Kristian Olson, MD, and Benjamin Bearnot, MD

When it comes to stopping the deadly effects of an opiate overdose, time is of the essence. Every moment that the brain is deprived of oxygen increases the risk of permanent damage or death. Overdoses can be reversed by administering a drug called Narcan, but the treatment has to be delivered quickly. A team of clinical specialists at Massachusetts General Hospital is hoping to revolutionize the way we respond to overdoses by putting Narcan in the hands of team of citizen volunteers who are ready to help whenever—and wherever—an overdose happens.

The Opioid Epidemic

There were 1,531 confirmed deaths attributed to opioid overdoses in Massachusetts in 2015, according to statistics recently released by the state. With the opioid epidemic continuing to spiral out of control nationwide, there’s a need to find a solution to curb the staggering number of deaths by overdose.

Help could be on the way thanks to an innovative new concept that emerged from a Fall 2016 hackathon put on by the Center for Affordable Medical Technologies (CAMTech) and Global Medicine at Mass General and sponsored by the GE Foundation.

The Allies Concept

The three-day hackathon provided an opportunity for three Mass General specialists—Kristian Olson, MD, the Medical Director of CAMTech and a core educator in the Department of Medicine, Benjamin Bearnot, MD, a primary care physician and Innovation Fellow at MGH Charlestown, and Jessica Moreno, PharmD, a clinical pharmacist at Mass General—to collaborate on a plan for reversing overdoses before they do lasting damage.

Olson, Bearnot and Moreno were part of a nine-person team that also featured an industrial designer, an engineer, an industry pharmacologist, and importantly, people in recovery.

Their plan, titled We Are Allies, calls for equipping everyday citizen volunteers with an easy to administer spray version of anti-overdose drug naloxone, commonly known by the brand name Narcan®.

Overdoses can be deadly because opiates bind to receptors in the brain and spinal cord that are responsible for keeping us breathing. When an overdose occurs, these receptors can slow down or stop working all together, which means the body can essentially “forget” to keep breathing. Naloxone reverses the effects of an overdose by releasing the hold that opiates have on the receptors.

It does not have an adverse affect on someone who is not having an opioid overdose, which makes it safe to administer if an overdose is suspected but not confirmed.

The team believes that getting naloxone into the hands of more people will increase the odds that someone will be nearby to help when an overdose occurs. Naloxone is relatively easy to get and safe to use, but many people—even doctors—don’t carry it with them on a regular basis.

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The Allies’ distinctive purple carrying case is designed to let others know that the person is carrying the anti-overdose drug naloxone

Another key component of the team’s plan is to have the Allies carry their naloxone in a bright purple pouch that can be attached to their handbag or workbag. This distinctive design will let others know that the person is carrying naloxone and is ready to help if needed.

“Not enough people have easy access to this life-saving medication, especially in situations where it is needed most,” says Moreno. “On top of that, those who do need it may be afraid or ashamed to seek it out due to the stigma they face every day. We hope to address both of these issues head-on by encouraging Allies to essentially wear the naloxone on their sleeves in our carrying cases.”

Reducing Stigma

The team hopes the high visibility purple pouches and indicator pins will also raise the public profile of the Allies in the community, which may help to foster new conversations about opioid use disorder and reduce the stigma and sense of isolation that many who suffer from the disorder experience.

“We thought that ‘ally’ was such a great term,” explained Olson. “We rallied around it because it changed the notion of isolation. We wanted to say; ‘We’re all allies in fighting opioid use disorder.’”

For more details on the program including training videos and information on how to sign up as an ally, please visit http://www.becomeanally.com/.

More than Just Hindering Fires – Can Flame Retardants Interfere with Fertility?

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In a new study published in Environmental Health Perspectives, a team of researchers investigated the potential connection between exposure to flame retardant chemicals found in household products— called PFRs — and pregnancy. While we can’t conclude from the results that products like yoga mats cause infertility, the findings bolster pre-existing research suggesting an association between PFRs and reproductive complications.

What are PFRs?
PFRs (organophosphate flame retardants) are a class of chemicals that are commonly used in the polyurethane foam in upholstered furniture, baby products such as nursing pillows, bouncers, and swings, and yoga mats (to name a few) to make them less flammable.

What’s the risk with PFRs?
They can spread from the foam into the air and dust. Considering the ubiquity of PFR-containing products, we likely inhale the chemicals on a regular basis without even knowing it. Although scientists don’t yet have enough conclusive evidence to say that PFRs are bad for our overall health, a growing body of research suggests exposure to PFRs can disrupt the hormones involved in reproduction and embryo/fetus growth. This new study expanded the evidence base by specifically looking at possible connections between exposure to PFRs and pregnancy.

What did the study involve and what did they find?
A team of researchers, including Mass General’s Russ Hauser, MD, MPH, ScD, followed 211 women who went to the Mass General Fertility Center to be evaluated for in vitro fertilization (IVF). The researchers checked the women’s urine for traces of PFRs and found that more than 80% of the women had traces of three types PFRs in their urine. After a cycle of IVF treatments, those with high levels of the chemicals were 31% less likely to have the embryo successfully implant in the uterus, 41% less likely to achieve pregnancy, and a 38% less likely to have a live birth than those with low levels.

What do the results mean? The research team looked at the correlation between traces of PFR and pregnancy outcomes but did not study whether PFR exposure was the cause of pregnancy complications.  Thus, we can’t conclude that exposure to PFR-containing products leads to infertility. However, the findings suggest an association between high levels of PFR exposure and poor pregnancy outcomes. Additionally, because researchers didn’t look at which specific PFR-containing products were the source of the chemical exposure, we can’t single out yoga mats or sofas as the culprits.

Are there limitations to the study?
The study participants were drawn from a small pool of women who were living in and around Boston, so it is not representative of the population at large. Plus, all participants were recruited from an IVF clinic, which suggests they many participants were predisposed to fertility issues coming into the study.

What’s next?
There’s an ongoing debate about the rational for putting flame retardants like PFRs in household products. Studies like this one provide compelling evidence for a potential association between PFR exposure and negative health outcomes like infertility, though more research needs to be conducted.  There are also questions as to how effectively PFRs prevent fires. In 2010, a group of 145 scientists from 22 countries published a statement detailing their concerns that flame retardants weren’t worth the health risks they posed.

What can people do to protect themselves in the meantime?
While it’s nearly impossible to fully avoid PFRs, consumers can minimize exposure by looking for products that have a natural flame retardant like leather or wool fabric, or seek out organic yoga mats. In a Huffington Post article, lead author Courtney Carignan of the Harvard T. Chan School for Public Health said that other precautions, like good-hand washing practices before meals, can also help lower levels of these chemicals in the body.

Evaluating the Impact of Cutbacks to HIV Programs in Resource-Limited Nations

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Proposed reductions in U.S. foreign aid would have a devastating impact on HIV treatment and prevention programs in countries receiving such aid, an international team of investigators reports. In their paper published online in Annals of Internal Medicine, the team led by researchers at Massachusetts General Hospital and the Yale School of Public Health describes how a 33 percent cutback in funds earmarked for HIV/AIDS prevention, treatment and research in recent budget proposals would only save $900 per year of life lost in the countries of South Africa and Côte d’Ivoire.

Read the full press release here.

Science Writing:  Nine Tips to Make Your Journal Articles Shine

Good science communication skills can be just as helpful when you are communicating with colleagues and journal editors as they are when you’re speaking to the public.

Here are nine helpful tips on writing journal articles by Anne Marie Weber-Main, PhD, and Anne Joseph, MD, MPH, from the University of Minnesota. You can find the complete presentation here.

  1. Clearly state the importance of your findings. What gap in knowledge did you address? What challenges did you overcome?
  2. Lead with your results, and then follow with explanatory details
  3. Provide rationale for your study design and methods if relevant to the results
  4. Include definitions of terms when appropriate
  5. Present information in a logical order, not necessarily a chronological one
  6. Use tables and figures for clarity and brevity
  7. Be consistent with terminology (For example, use either “aggression” or “aggressive behavior,” but not switch back and forth between the two)
  8. Similarly, using parallel sentence structure can be helpful when comparing methodology and results between data sets (helps the reader understand the similarities and differences when information is presented in a consistent way)
  9. Make specific suggestions for how future research could expand upon your results

Adapted from:
Foundations of Scholarly Writing (Session 3)
Meeting Readers’ Expectations for IMRaD |Responding to Reviewers
By Anne Marie Weber-Main, PhD, and Anne Joseph, MD, MPH

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