Month: October 2016

Researchers discover “brain signature” for fibromyalgia using brain scans

portrait-1006703_1280Millions of patients suffering from fibromyalgia often experience widespread musculoskeletal pain, sleep disturbances, fatigue, headaches and mood disorders. Many also struggle to even get diagnosed, since there are currently no laboratory tests for fibromyalgia and the main symptoms overlap with many other conditions. However, new research may help.

Scientists from the University of Colorado, Boulder may have found a pattern of brain activity that identifies the disease. They used functional MRI (fMRI) scans to study the brain activity of 37 fibromyalgia patients and 35 matched healthy controls, while the participants were exposed to a series of painful and non-painful sensations.

As reported recently in the journal PAIN, the research team identified three specific neurological patterns correlated with fibromyalgia patients’ hypersensitivity to pain.

Using the combination of all three patterns, they were able to correctly classify the fibromyalgia patients and the controls with 92 percent sensitivity and 94 percent specificity — meaning that their test accurately identified 92 percent of those with and 94 percent of those without the disease.

Tor Wager, PhD, senior author and director of the school’s Cognitive and Affective Control Laboratory, explained the significance of the work in a recent news release:

“Though many pain specialists have established clinical procedures for diagnosing fibromyalgia, the clinical label does not explain what is happening neurologically and it does not reflect the full individuality of patients’ suffering. The potential for brain measures like the ones we developed here is that they can tell us something about the particular brain abnormalities that drive an individual’s suffering. That can help us both recognize fibromyalgia for what it is – a disorder of the central nervous system – and treat it more effectively.”

More research is needed, but this study sheds a bit of light on this “invisible” disease.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Discussing cancer: Online course offers tips to tackling tough conversations

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Photo by Serena Wong

Have you tried to talk to a friend or family member about cancer? It’s not easy. You might have blurted out something offensive, offered advice you weren’t quite sure about, or tried to minimize cancer’s severity or prevalence. Or maybe you just avoided the conversation entirely.

Even those with medical training struggle with cancer discussions. In response, a London-based nonprofit has created a free online course called “Talking About Cancer,” which offers strategies for discussing cancer risks, preventing and screening.

The three-hour course — which is designed for health-care workers, counselors, volunteers and others — is organized into short, self-paced modules made up of videos, quizzes, online discussions and role-playing with actors. I recently spoke with one of the course organizers, former journalist and Stanford alumni David Risser.

What is the course like?

“The course quickly reviews cancer myths and facts, and then concentrates on how to have confident conversations about cancer prevention. It’s an important area, because more than four in ten cancer cases could be prevented by lifestyle changes. Another goal is to boost early diagnosis, by training people to encourage others to see a doctor.

We wanted to present an engaging course with varied activities, including a ‘real-life’ narrative that runs through the course. We hired improv actors to play two characters, Anita and Brian. Anita has health difficulties but is reluctant to see a doctor. Brian feels invincible, but has multiple habits — smoking, drinking too much, a poor diet, and even refusing to use sunscreen — that put him at higher risk… We were amazed at how strongly participants identified with the experiences of these characters, leading to passionate discussions about effective ways to talk about cancer.

The course is led by our cancer awareness trainers — two nurses with experience in engaging doctors, nurses and people without medical training. It’s open now, but you must sign up by October 31. Otherwise, we plan to offer another free, public run of the course early next year.”

What inspired you to get involved?

 “I am a Stanford graduate with a B.A. in history, and a past managing editor of The Stanford Daily. I joined Cancer Research UK after a 28-year career in journalism, in part because of my own experience with several family members who have had cancer. I struggled to talk to one family member who didn’t seem to want to talk about her cancer. That made it easy for me to avoid talking about it, which wasn’t the ideal outcome.

It was also difficult to talk to another family member about being more proactive about her medical care, which was inadequate at the start. It’s still difficult to know whether or how to talk to friends about prevention.”

What have you learned while working on this project?

“I learned that there are widespread gaps in knowledge about cancer, from causes to treatments to chances of survival. For example, many people don’t know that obesity is the second most-preventable cause of cancer or that alcohol is linked to a range of cancers.

I think the most common mistake when talking about cancer is feeling you have to know everything. It’s more effective to say ‘I don’t know, how do you think we can find out?’ or `What have you thought about doing?’ than to avoid the subject, make pronouncements or communicate incorrect information. Another common mistake is failing to listen, listen, listen, rather than fix everything. Sometimes it’s better to guide the person through what they are feeling and what they are concerned about, keeping it about them and not about you or your solutions. The bigger issue in both cases is to gently help people see what they can do that works for them.

While the course focuses on cancer information, prevention and early diagnosis, most of it is about how to have conversations about difficult subjects. The greatest lesson in the course is how to talk to people in ways that encourage behavior change. And that can save lives.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Calcium the conductor: New role found for mineral in bone development

It isn’t news that we need calcium to keep our bones dense and strong. If you don’t get enough calcium in your diet, or if your body doesn’t absorb enough, your bones can become brittle and fragile. But calcium is more than just an essential part of your bone structure. A new research study shows that it also plays a major role in regulating the cells that control bone formation.

Biochemist Michael Rape, PhD, and his colleagues at University of California, Berkeley studied how bone cells form in very early embryos. In particular, they investigated neural crest cells that help develop bones in the head and face. Without enough neural crest cells, an embryo dies or has a craniofacial disorder like Treacher Collins syndrome, which is characterized by deformed ears, eyes and cheekbones.

The Berkeley researchers weren’t expecting to discover a new role for calcium. Instead, they were investigating how to turn on enzymes like CUL3 to form normal, healthy bones. Previous research showed that CUL3 enzymes can trigger undifferentiated stem cells to become neural crest cells during embryo development. In this study, the team learned that calcium is essential to help CUL3 trigger proper bone growth — surprising results that were recently reported in Cell.

As Rape explained in a recent news release:

“Our research basically identifies calcium not only as a structural element of bone, which makes the bone strong and sturdy, but also as a signaling molecule for bone formation that we hadn’t appreciated before, which can be used to turn enzymes on and off. …. This means that you basically have many different steps that come together in order to form a bone, and that they are beautifully orchestrated by calcium.”

This research became more personal to Rape when he was visited by Francis Smith, PhD, a Treacher Collins syndrome patient and postdoctoral research fellow at the University of Colorado. Rape said in the video above, “When you talk to patients of a disease, it shows you the direct consequences of your work and the urgency of your work becomes much more apparent.”

Further research is needed before these results can be used to help trigger proper bone growth for patients, but the researchers are hopeful. “The more you understand about each of these steps, the easier it is to focus your applied research onto things that matter and change something for these patients,” Rape said in the news release.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Curious about concussions? A Stanford researcher reflects on current research, outstanding questions

Photo by Steve - Body Slam
Photo by Steve – Body Slam

Football season has begun, reviving concern and discussion over sports-related concussions.

The American Academy of Pediatrics defines a concussion as a direct hit to the head or jarring blow to the body that gets transmitted to the head, resulting in a rapid onset of short lived impairment of neurological function. However, some controversy surrounds even this definition. So I reached out to Jessica Little, PhD, director of clinical research and operations at the Stanford Concussion and Brain Performance Center, to learn more about concussion research and Stanford’s clinical study of teenage athletes.

What should we know about concussions?

“I think it is important to note that concussions are still not well understood. There are hundreds of different definitions of ‘what is a concussion’ and there is currently no single evidence-based consensus on how to identify and treat concussions.

Research has shown that one of the biggest risk factors for sustaining a concussion is a history of having a prior concussion. There is a ‘window of vulnerability’ — the concept that a person experiencing symptoms of concussion is more vulnerable to incurring a second concussion during this time, as the brain has not yet fully recovered. If a truly concussed athlete has problems paying attention or is not coordinated, they can then be vulnerable to another injury. Protocols are often used to track signs and symptoms of concussion, and athletes are not allowed to return to play until these have resolved. However, it would be helpful to have more precise ways to measure attention and coordination on the sidelines to keep impaired athletes out of contact sports until those skills recover.

The vast majority of people with a concussion recover fully after the injury, though not all symptoms may improve at the same rate and everyone recovers a little differently.”

Describe your clinical study for athletes between 12-17 years of age.

“Our study just closed recruitment and we’re prepping all the data for analysis, so it is an exciting time. The study was called EYE-TRAC Advance, short for Eye-Tracking Rapid Attention Computation. Our lab used a specific type of eye-tracking called ‘circular smooth pursuit’ where an athlete follows a dot that moves at predictable speed around a circle. The eye-tracking was in the form of custom-designed portable “goggles,” using built-in cameras and infrared pupil detection.

Our hypothesis is that people without a concussion can ‘sync-up’ with the way the dot is moving pretty easily, while a person with a concussion has a disruption in their ability to focus and pay attention. You often hear people saying that they feel “off” or “out of sync” following a concussion, and we’re trying to quantify that experience. For the study, we baseline tested athletes (before sports participation) with the eye-tracking, as well as other neurocognitive tests that measured things like attention and reaction time. If the athlete later got a concussion, we tested them again as soon as possible and again at 1, 3 and 12 months after the injury. In this way, we’re able to get a clear picture of how their brain recovered over time.

Overall, we reached out to over 60 different organizations and recruited over 1,400 people. We had a specially outfitted ‘mobile testing center’ RV. This allowed us to literally drive up to the side of an athletic field and perform the testing on-site at the school or organization, which really reduced common barriers to participating in a research study, such as the costs and time associated with transportation to and from appointments.”

Can technology play a significant role in preventing concussions?

“A lot of current technologies focus on diagnosing a concussion, but there are far fewer that actually focus on preventing concussions. There are some technologies that measure an athlete’s gait and vestibular-balance ability. If there are impairments, the athletes can be provided skill training to improve any deficits, thus reducing the risk of injury. Other technologies, such as helmet technologies, may be helpful in reducing the instance of skull fractures and other serious injuries, but they haven’t yet proved effective at preventing a concussion — that is caused more by brain rotation, which a helmet can’t fully protect against. One possible preventative solution could come from a neck device that stabilizes the rotational forces while still allowing neck movement at low accelerations, so athletes can move about freely until it senses a potentially dangerous level of force.”

Are there issues with under-reporting concussions?

“Historically, there have been some issues with individuals under-reporting symptoms that would lead to a diagnosis of a concussion. This is often motivated by the idea that they should ‘suck it up,’ ‘don’t want to let the team down’ or the fact that their ability to perform athletically is tied to keeping an athletic scholarship. There is research happening in the field right now trying to figure out the best way to dismantle these types of beliefs and make it more likely that athletes can be properly identified, given the treatment they need, and hopefully continue to safely engage in their sport.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Stanford medical student illustrates mnemonics

Illustration courtesy of Nick Love
Illustration courtesy of Nick Love

Medical students frequently turn to mnemonics to master human anatomy, but they’re usually just catchy phrases. Now, Nick Love, a second-year Stanford medical student, has created a more entertaining way to memorize anatomy: a set of illustrated mnemonics, which he has published in the form of a book and website. I recently spoke with Love about his project.

What inspired you to illustrate the anatomic mnemonics?

“When I began medical school, I was totally unaware as to the central role mnemonics play in medical education and beyond. They are everywhere! Their sometimes wacky and ridiculous wordings intrigued me — I wondered if they could serve as a unique source of ‘found imagery,’ starting points for visual exploration. I brought up this idea with Audrey Shafer, MD, director of the Biomedical Ethics and Humanities medical school track, and she kindly encouraged me and linked me up with an awesome mentor for the project, pediatric anesthesiologist and painter Samuel Rodriguez, MD.”

Where did you get the mnemonics and how did you choose your illustration style?

“They are all essentially common med school mnemonics. Fourteen of the 16 mnemonics were passed on to us as medical students, mainly by our clinical anatomy teaching assistants via the ‘whiteboards’ in the anatomy lab. I sourced one mnemonic directly from the internet, and I altered another because its original form was too raunchy for publication. At the moment, I am, unfortunately, too behind on too many things to add more.

In terms of illustration, I was motivated to try a digital-analog-digital process. I’m currently intrigued by combining the reproducibility of computer-aided illustration with the inherent chaos of spreading paint or ink. Also, I wanted to maximize color usage, insert a bit of whimsy into the illustrations and experiment with recursive imagery.”

Do you have a favorite mnemonic?

“My favorite mnemonic is ‘canned soup, really good in cans.’ It helps one remember the branches of the descending aorta — canned soup, really good in cans, representing celiac, superior mesenteric, renal, gonadal, inferior mesenteric, and common iliac arteries. The phrase ‘canned soup, really good in cans’ strikes me as rather humorous, like it was made for an ad campaign when soup was first put into cans. Genius, whoever came up with it.”

Do you have any art training? Who are your favorite artists?

“Before coming to medical school, my training was mainly in science. However, last year I took two art classes at Stanford, ‘Digital Photography’ and ‘Video Compositing,’ both of which were awesome. As a kid, I mostly played sports, video games and outside. The desire to make things came later.

My favorite artists include Alphonse Mucha, David Hockney, Kiyoshi Yamashita and Andy Warhol. Currently, my favorite museums are the Cantor Arts Center and the Anderson Collection — right here at Stanford and only about 1 km from the medical school! I also try to go to the Tate Modern when I’m in London.”

Do you hope to include art somehow in your future medical practice?

“I’m very much interested in learning more about what is referred to as the ‘art of medicine,’ and I hope to have the time to keep creating. At the moment, I’m most drawn to visually-based medical specialties, such as dermatology, pathology, radiology and nuclear medicine.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Genomic analysis allows researchers to identify three subtypes of prostate cancer

Photograph by Raul654
Photograph by Raul654

Many men with prostate cancer have slow-growing tumors that don’t require aggressive treatments such as surgery or radiation therapy, whereas others have rapidly-growing prostate tumors that are life threatening. Distinguishing between these patients with indolent versus aggressive disease is a major challenge, but researchers have just made a significant step towards identifying genetic risk factors for prostate cancer prognosis.

A multi-institutional research team has identified three distinct molecular subtypes of prostate cancer, which are correlated with survival rates and may guide future treatment planning. Their study results were presented at the annual meeting of the American Society of Radiation Oncology by Daniel Spratt, MD, an assistant professor in radiation oncology at the University of Michigan Heath System.

Spratt explained in a recent American Society of Radiation Oncology press release:

“Tumors that appear similar under a microscope can behave very differently, from a clinical standpoint. One promise of genomic analyses is to elucidate subtypes of cancer based on the genetics of the tumor rather than merely how they look or what size they are.”

The research team analyzed the RNA expression patterns of 4,236 primary prostate cancer samples taken from nine independent groups of men, who had their prostate surgically removed to treat primary prostate cancer. The investigators’ statistical clustering analysis identified three distinct patient groups based on 100 key genes, which they named the Prostate Cancer 100. These study results were then validated using samples from over 2100 patients.

The subtypes were found to be correlated with androgen receptor activity, ERG oncogene expression and other factors known to promote prostate tumor growth. They were also correlated with how long patients survived without metastasis. The distant metastasis-free survival rates varied among the three subgroups — 73.6 percent for group A, 64.4 percent for group B and 57.1 percent for group C — showing that subtype A patients had the most favorable prognosis.

Furthermore, the study found that subtype B and C patients responded significantly better to postoperative radiation therapy, which was used after the prostate was surgically removed in order to kill any remaining cancer cells. This is important because radiation therapy has many potential side effects, including impotence and incontinence.

Spratt summarized in the press release:

“We believe that these subtypes reflect truly distinctive underlying biology and that this work represents a significant advance in our understanding of prostate cancer biology. Moreover, our findings identify numerous genes and enriched biologically active pathways in prostate cancer that have been underappreciated to date but may be potential targets to improve cure rates in this disease by developing new targeted therapies.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Can social media shed light on cardiovascular disease? Possibly, Stanford journal editors write

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Illustration by Clker-Free-Vector-Images

Clearly social media is part of our every day lives, recording our personal communications in a way previously unimaginable.

Researchers are now analyzing this wealth of social media data to better understand what people think and say about their health. Recently, researchers at the University of Pennsylvania sifted through 10 billion English-language tweets to identify and study more than 550,000 US-based tweets related to cardiovascular disease, as reported in JAMA Cardiology.

The research team found that people who tweeted about five cardiovascular conditions — high blood pressure, heart attack, diabetes, heart failure and cardiac arrest — were more likely to be older and female compared to the general population of Twitter users. They also tweeted within minutes or hours in response to events, such as celebrity deaths or to mark World Diabetes Day. 

This study was discussed in the issue’s Editor’s Note by Stanford journal editors Mintu Turakhia, MD, an assistant professor of medicine, and Robert Harrington, MD, a professor and the chair of the Department of Medicine. In the editorial, they acknowledged that the Penn Twitter study was atypical research to include in JAMA Cardiology but noted that digital health is now a major priority for the journal. They explained:

“We accepted [the paper] because it highlights the potential for using these emerging data sources such as Twitter for cardiovascular research, in this case to evaluate public communication about cardiovascular medicine in a manner not previously possible on such a scale.”

Turakhia, the journal’s associate editor of digital health, elaborated in an email: “Twitter and other social media data allow us to examine daily interactions in a connected life in ways not possible before,” he said. “Previously, in order to gain insight on the public’s perception or interest in cardiovascular disease, we were limited to examine historical news and media archives or direct surveys.”

Although the editors believe that Twitter is a new and important research tool, they raised a few questions about future studies. They wrote in the editorial, “The use of Twitter and other social media platforms for cardiovascular research is in an early, proof-of-concept stage. Many important questions remain: Is there signal in the noise? Are these data or results… from the ‘Twitterverse’ generalizable to a broader population?” They also emphasized the need to establish analysis standards and overcome any ethical issues in linking the data with medical or clinical information. Turakhia added:

“Twitter users do not represent the broader population, but that’s not really its purpose. Twitter allows us to examine a highly connected subset of society and learn how cardiovascular disease might manifest in their connected world.”

Ultimately, researchers hope to use this new information to improve their patients’ health, but the research is in its infancy, he said, adding:

“We haven’t yet figured out how Twitter or social media can be definitely used to improve health and health care. The obvious avenues would be through social and community engagement. Although sharing of personal information is at the cornerstone of the success of social media, I’m not sure that society is ready to be as open with posting health information, as they are with selfies or pictures of kids. However social media could be used to gamify health care behavior by providing incentives, and that won’t need disclosure.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

To battle mosquito-borne disease, SLAC x-ray laser provides new view of insecticides

Illustration, of LCLS x-ray pulses blasting BinAB nanocrystals composed of protein BinA (yellow) and BinB (blue), courtesy of SLAC National Accelerator Laboratory.
Illustration of LCLS x-ray pulses blasting BinAB nanocrystals composed of protein BinA (yellow) and BinB (blue), courtesy of SLAC National Accelerator Laboratory.

Mosquitoes continue to spread devastating diseases such as malaria, West Nile virus, dengue fever and Zika virus throughout the world. Sadly, there are no medications or vaccines for many of these deadly diseases, so it’s critical to prevent mosquito bites.

A cost effective way to eliminate these disease-bearing insects is the use of specialized insecticides that target against the larval stage of a mosquito. These larvicides, like BinAB, kill some mosquito species, but they are currently ineffective against Aedes mosquitoes that transmit Zika and dengue fever. Now, an international team of researchers is working to develop a new toxin that will kill a broader range of mosquito species, including Aedes.

The existing larvicide BinAB is composed of two proteins, BinA and BinB, which pair together to form nanocrystals inside Lysinibacillus sphaericus soil bacteria. When these bacteria are distributed on the surface of stagnant water locations where mosquitoes breed, the mosquito larvae eat the bacteria — dissolving the nanocrystals that bind to their gut, activating the deadly BinAB toxin and killing the larvae.

The proteins are toxic to the mosquitoes, but harmless to humans and other animals. Unfortunately, previous research has shown that BinAB is also harmless to an Aedes mosquito, because the protein never binds to the insect’s gut so the toxin isn’t activated.

“Part of the appeal is that the larvicide’s safe because it’s so specific, but that’s also part of its limitation,” said Michael Sawaya, PhD, a scientist at the UCLA-DOE Molecular Biology Institute, in a recent news release.

Now, the researchers are adapting the BinAB toxin to attack mosquito species that are insecticide resistant. In order to do this, they needed to understand the 3-D structure of the BinAB proteins and how they work. This was a challenge, because the nanocrystals were so tiny and their structural details were a mystery.

The research team increased the size of the nanocrystals using genetic engineering, and then blasted them with an intense beam of bright, fast pulses of light using the Linac Coherent Light Source (LCLS) at the SLAC National Accelerator Laboratory. This allowed the team to collect detailed structural data from the tiny crystals and create 3-D maps of the electron density of the BinAB protein, as reported in a recent paper in Nature.

The LCLS experiments helped the researchers fully understand how the BinAB protein forms and functions. They are now engineering a modified version of the protein that will kill a broader range of mosquito species.

“The most immediate need is to now expand the spectrum of action of the BinAB toxin to counter the progression of Zika, in particular,” said Jacques-Philippe Colletier, PhD, a scientist at the Institut de Biologie Structurale in France, in the news release. “BinAB is already effective against Culex [carrier of West Nile encephalitis] and Anopheles [carrier of malaria] tos. With the results of the study, we now feel more confident that we can design the protein to target Aedes mosquitoes.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.