“A toxicological experiment:” Additional study needed on e-cigarettes use

Posted April 12, 2018 by Jennifer Huber
Categories: Health

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Photo by Itay Kabalo

Although the market for e-cigarettes is booming, scientists and health agencies are still debating the extent of their health impacts. Basic questions remain: What chemicals are in the vapor cloud produced by e-cigarettes? And how does this vapor affect users and those around them?

A research team led by Hugo Destaillats, PhD, a chemist in the Indoor Environment Group at Lawrence Berkeley National Lab, is seeking the answers to these questions.

Destaillats and his colleagues have studied the complex chemical composition of vaping aerosols, the cloud of particles the devices emit. In one study, they quantified emissions from three e-liquids with various vaporizers, battery power settings and vaping habits — ranging from heavy to low puff duration and frequency.

The researchers found 31 potentially toxic substances in the vapors, including two not previously detected: propylene oxide in the e-liquids and glycidol in the vapors. Both of these compounds are considered probable carcinogens. They also determined that the base fluids used in vaping, propylene glycol and glycerin, can decompose when heated to produce acrolein, a powerful irritant.

However, the level of these toxins varied depending on the type of e-cigarette and how it was operated. For instance, toxic emissions rates were higher for e-cigarettes with a single heating coil compared to ones with double coils. Toxin levels also increased with the voltage used to power the device. And they rose with repeated use, presumably due to a buildup of residue within the device.

“We hope that one outcome of our research has been to provide useful information to manufacturers to help them improve the safety of their devices,” said Destaillats in a recent article in Analytical Scientist. .

In a follow-up study, the researchers assessed the health impact of firsthand and secondhand exposure to these vapor clouds under various typical use conditions. The integrated health damage from vaping for the various scenarios was lower than, or comparable to, the estimated damage from tobacco smoke, they concluded.

Given the countless unique e-liquid flavors and the on-going development of new devices, this research is difficult to generalize, they said, but they are concerned that more unidentified toxins exist.

Destaillats summarized in the article:

“Vaping is effectively a toxicological experiment being carried out with millions of people around the world.”

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

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New way to understand tumor diversity combines CRISPR with genetic barcodes

Posted April 10, 2018 by Jennifer Huber
Categories: biology, Health

Tags: , , ,

Photo courtesy of PIXNIO

The growth of a particular tumor depends on multiple genetic factors, so it is difficult for cancer researchers to recreate and study this genetic diversity in the lab.

“Human cancers don’t have only one tumor-suppression mutation [which fuels tumor growth] — they have combinations. The question is, how do different mutated genes cooperate or not cooperate with one another?” said Monte Winslow, PhD, a Stanford assistant professor of genetics and of pathology, in a recent Stanford news release.

Now, Winslow and his colleagues have discovered a way to modify cancer-related gene and then track how these combinations of mutations impact tumor growth, as recently reported in Nature Genetics.

The researchers used a powerful gene-editing tool, called CRISPR-Cas9, to introduce multiple, genetically distinct tumors in the lungs of mice. They also attached short, unique DNA sequences to individual tumor cells — which acted as genetic barcodes and multiplied in number as the tumors grew. By counting the different barcodes, they were able to accurately and simultaneously track tumor growth.

“We can now generate a very large number of tumors with specific genetic signatures in the same mouse and follow their growth individually at scale and with high precision. The previous methods were both orders of magnitude slower and much less quantitative,” said Dmitri Petrov, PhD, a senior author of the study and an evolutionary biologist at Stanford, in the release.

The study showed that many tumor-suppressor genes only drive tumor growth when other specific genes are present. The researchers hope to use their new methodology to better understand why tumors with the same mutations sometimes grow to be very large in some patients and remain small in others, they said.

Their technique may also speed up cancer drug development, allowing a drug to be tested on thousands of tumor types simultaneously. Petrov explained in the release:

“We can help understand why targeted therapies and immunotherapies sometimes work amazingly well in patients and sometimes fail. We hypothesize that the genetic identify of tumors might be partially responsible, and we finally have a good way to test this.”

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

Oncologist disagree on use of value to guide cancer treatments

Posted April 5, 2018 by Jennifer Huber
Categories: Health

Tags: ,

Cancer care is expensive, with the cost of new chemotherapies exceeding  $100,000 annually and the growth in cancer care costs increasing faster than the growth in general medical care costs. In addition, there is a widely acknowledged mismatch between the costs and benefits of treatment.

“The pricing of cancer drugs doesn’t appear to be related to their health benefit. This is problematic and unaffordable both for the health care system and for patients, who are expected to engage in not-insubstantial cost sharing,” explained Risha Gidwani-Marszowski, DrPH, a health economist at the VA Palo Alto Health Care System and at Stanford.

In response to this gap, oncology professional societies now recommend that oncologists consider the value of a treatment when making clinical recommendations, a major shift in clinical practice. But how are oncologists defining whether a therapy has “high value?” And how are they using this information?

Gidwani-Marszowski investigated these questions in a new study recently published in Value in Health. Her multi-institutional research team conducted in-depth interviews with 31 U.S. oncologists who practiced in a diverse range of environments, including academic medical centers, community medical centers and the Veterans Health Administration.

The researchers asked oncologists open-ended questions about larger questions regarding value – specifically,  about the oncologists’ definitions and measurements of value, as well as about their value-based choices.

“We didn’t want to operate under the erroneous assumption that we knew everything there is to know about the relevant features of the value problem,” said Gidwani-Marszowski. “We felt it would be better to keep things open-ended, so that practicing oncologists could tell us the aspects of value that were most relevant or salient to them.”

Once these in-depth conversations were transcribed, two independent investigators qualitatively assessed the transcripts to identify themes — pinpointing and recording patterns. Their analyses revealed that oncologist have wide ranging views. Gidwani-Marszowski explained:

“One of the most interesting things we found through this work is that the divergent views exist at a very basic level — the definition of value.  For example, in defining value, some oncologists said cost was one of multiple factors that should be considered, while others said cost had no role at all to play in value.”

Additionally, some oncologists looked at cost in relation to a patient’s quality of life, while others looked at quality of life alone to measure value. One oncologist explained in the paper, “I think [value] shouldn’t just be measured by overall survival, but quality of life has to really be integrated into that. I’m extending the patient’s life by two months, if they’re filled with chemotherapy side effects and toxicity, have we increased the value?”

The oncologists also disagreed on how value should be measured, who should assess the value of a treatment and whether value should be discussed with the patient.

For one oncologist, conversations about costs are important: “I tend to explain to them what the cost is and what the benefit is. And some patients actually say, ‘I don’t think it’s worth it.’ … So I will give them [information about the] cost and the side effects and the benefit and we’ll make the decision together.”

For another oncologist, the conversations don’t work well: “Most of the time we don’t [discuss the cost of care] because then the patients and families think hey, these guys are looking at dollars and not providing the care… So that’s kind of really controversial. Plus it’s very uncomfortable even to talk about the money and the care we provide to them…”

Now, the team is using the results from these in-depth interviews to design a closed-ended survey, which they plan to disseminate to a large sample of oncologists across the country. Gidwani-Marszowski explained:

“Oncologists often have the best understanding of the effectiveness of a particular drug in a specific patient and largely guide the purchasing of care for cancer patients. Thus, it is partly through understanding their perspectives that we can improve the value of cancer care.”

Gidwani-Marszowski also told me that for value efforts to be successful, a critical first step is to make sure all of the relevant stakeholders — oncologists, patients, caregivers, other health care providers, payers, health economists and policy makers  — are able to reach a consensus on the definition of value in cancer care.  That will build a foundation for efforts to establish thresholds for value, mechanisms to measure value, and ultimately, efforts to improve the value of cancer care, she said.

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

Stanford and Common Sense Media explore effects of virtual reality on kids

Posted April 4, 2018 by Jennifer Huber
Categories: Health, Technology

Tags: , ,

Photo by Andri Koolme

Although we’re still a long ways off from the virtual reality universe depicted in the new movie “Ready Player One,” VR is becoming a reality in many homes. But how is this immersive technology impacting our kid’s cognitive, social and physical well-being?

Stanford researchers and Common Sense Media are investigating the potential effects of virtual reality on children. And a  just-released report provides parents and educators with a practical guide on VR use.

“The truth is, when it comes to VR and kids, we just don’t know that much. As a community, we need more research to understand these effects,” Jeremy Bailenson, PhD, a Stanford communication professor and the founder of Stanford’s Virtual Human Interaction Lab, wrote in an introduction to the report.

The research team surveyed over 3600 U.S. parents about their family’s use of virtual reality. “Until this survey, it was unclear how, and even how many, kids were using virtual reality,” said Bailenson in a recent Stanford news release. “Now we have an initial picture of its adoption and use.”

The report summarizes results from this survey and previous VR research. Here are its key findings:

  • VR powerfully affects kids, because it can provoke a response to virtual experiences similar to actual experiences.
  • Long-terms effects of VR on developing brains and health are unknown. Most parents are concerned, and experts advocate moderation and supervision.
  • Only one in five parents report living in a household with VR and their interest is mixed, but children are
  • Characters in VR may be especially influential on young children.
  • Students are more enthusiastic about learning while using VR, but they don’t necessarily learn more.
  • VR has the potential to encourage empathy and diminish implicit racial bias, but most parents are skeptical.
  • When choosing VR content, parents should consider whether they would want their children to have the same experience in the real world.

Ultimately, the report recommends moderation. “Instead of hours of use, which might apply to other screens, think in terms of minutes,” Bailenson wrote. “Most VR is meant to be done on the five- to 10-minute scale.”  At Stanford’s Virtual Human Interaction Lab, even adults use VR for 20 minutes or less.

One known potential side effect from overuse is simulator sickness, which is caused by a lag in time between a person’s body movements and the virtual world’s response. Some parents also reported that their child experienced a headache, dizziness or eye strain after VR use.

In addition, the researchers advise parents to consider safety. Virtual reality headsets block out stimuli from the physical world, including hazards, so users can bump into things, trip or otherwise harm themselves.

A good option, they wrote, is to bring your child to a location-based VR center that provides well-maintained equipment, safety spotters and social interactions with other kids.

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

Learning from health-related social media posts: A Q&A

Posted March 29, 2018 by Jennifer Huber
Categories: Health

Tags: , , ,

Image by Max Pixel

About 6,000 tweets are sent every second and they aren’t all about celebrities. Posts about health or illness can be tremendously valuable to health care professionals, allowing them to track trends, spot epidemics and assess the quality of services provided by health facilities, to name just a few uses.

But how can the researchers make sense of this flood of data? To find out, I spoke with Sidhartha Sinha, MD, an assistant professor of medicine at Stanford, who analyzes social media posts to better understand patient and societal perceptions.

What sparked your interest in online data?

“While there are certainly downsides with working with unstructured data from sources such as social media and online patient forums, there are also tremendous advantages, including the scope of patients we can ‘reach.’

For example, in our work analyzing data from an online patient forum for patients with inflammatory bowel disease, we are able to access tens of thousands of posts from patients with IBD. These patients are describing a variety of issues around their experience with the disease — such as their therapy side effects (some of which have not been seen before and may offer early insights), psychosocial issues with chronic disease, and opinions regarding treatments and interventions. By analyzing this data, we are in effect  ‘listening’ to these patients’ experiences and hopefully gaining insights to better treat the disease.”

I understand you’ve also used online data to better understand public sentiment — could you describe that?

“One of the most important things health care providers do is try to prevent disease.  And one of the best means to do this is through disease screening.  However, millions of people do not get age-appropriate screening for diseases such as breast cancer or colon cancer.  My group’s initial work targeted understanding the perceptions around cancer screening tools.  Understanding how people feel about these screening interventions — particularly on the scale we’re able to examine using social media — allows us to not only identify barriers, but also further ascertain methods that work.”

How did you do that?

“Tens of thousands of tweets mentioning screening tests are created weekly. And while there are clear limitations to the quality of data and its generalizability, the sheer volume of data that we can access is much larger than most other means such as conventional surveys, which carry their own significant limitations. So we developed and validated a machine learning algorithm to classify sentiment (positive, negative, or neutral) around mentions of three common cancer screening tools: colonoscopy, mammography and PAP smears.

We found more negative sentiment expressed for colonoscopy and more positive sentiment for mammography. For example, the words ‘fear’ and ‘pain’ were commonly associated with negative sentiment. We also found that posts that were negative in sentiment spread more rapidly through social media than positive posts.”

How are these findings being used?

“Knowing the types of postings that reach more users, and some of the common issues expressed in them, could certainly influence how professional societies develop outreach interventions to improve engagement with preventive health efforts.

Based on our initial findings, we are developing additional algorithms to hopefully butter understand patient and societal perceptions of disease. We are also now engaged with professional societies such as the Crohn’s and Colitis Foundation to provide organizations with improved methods to understand patient needs and promote health.”

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

Big bacteria may be easier to kill, new research suggests

Posted March 21, 2018 by Jennifer Huber
Categories: biology, Health

Tags: , , ,

Image by NIAID

The size of a cell is intrinsicThe size of a cell is intrinsically linked with its genetic makeup, growth rate and other fundamental properties. What would happen if scientists could control the size of pathogens?

That possibility isn’t completely outlandish: Stanford researchers have discovered a genetic “tuning knob” that can enlarge or shrink bacteria across a wide range — and this knob can be used to fatten up the bacteria to increase their susceptibility to certain antibiotics, as recently reported in Current Biology.

The research team is led by KC Huang, an associate professor of bioengineering and of microbiology and immunology at Stanford. Huang explained in a recent Stanford Engineering  news article:

“Most strategies to killing bacteria are linear: you find a very specific target and block it with a drug. These findings point in the direction of totally orthogonal therapies, in which you predispose cells to death by tweaking a global property like size.”

The researchers found that a single protein in E. coli, called MreB, acts as a master regulator of cell size by coordinating the construction of cell walls. So they manufactured many copies of the E. coli’s DNA, changing in each copy just one of the 347 letters in MreB’s genetic code. Using fluorescence-activated cell sorting, they then separated the individual cells with different sizes to create a library of cell-size mutants.

The team used this library to study how size impacts a cell’s physiology, including how bacterium grow and survive. For instance, they treated the various E. coli mutants with several antibiotics and found that larger E. coli were more sensitive to the drugs. A larger cell has more surface area and that increases the drug uptake, they said in the paper.

Huang said he hopes their techniques can be applied to other bacteria and used to help human health in the future. He added:

“While we don’t yet know how to twist this bacterial size dial in patients, it’s good to have such an exciting new therapeutic approach as antibiotic resistance becomes increasingly prevalent.”

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

 

Developing “guided missiles” to attack cancer: A podcast featuring a Stanford bioengineer

Posted March 16, 2018 by Jennifer Huber
Categories: biology, Health

Tags: ,

Photo by Allocer

Chemotherapy attacks cancer by killing cells that are rapidly dividing. But this leads to serious side effects, like intestinal upset and hair fallout, because these normal cells grow quickly.

So researchers like Jennifer Cochran, PhD, a professor and the chair of bioengineering at Stanford, are developing more targeted cancer therapies, dubbed “guided missiles.” She recently described her work to professor and radio show Russ Altman, MD, PhD, on an episode of the Sirius radio show The Future of Everything.

“We, and others, have developed novel proteins that can selectively target cancer cells and then we can attach cargo to them — this is where the missile analogy comes in,” Cochran told Altman. “The cargo that we attach, things like chemotherapy, can then be selectively targeted to the tumor.” The idea is to precisely deliver to the tumor a more poisonous dose than you could deliver systemically, she said.

One way to do this is to bioengineer antibodies, which are molecules that recognize and help neutralize foreign substances like bacteria. However, Cochran’s lab took a slightly different approach. She explained to Altman:

“As amazing as antibodies are, they can have some limitations in that they are very large in terms of molecular size so they have trouble wiggling into a tumor. So we’ve created smaller versions of tumor-targeting proteins that can hopefully penetrate into tumors better. And we’ve then chemically attached chemotherapy molecules to deliver a punch to the cancer cells.”

In order to develop these proteins, her team is expediting protein evolution in a test tube — making favorable properties that would normally evolve over millions of years happen in just a few weeks. To do this, the team uses genetic manipulation to create millions of slightly different protein variants, tests them with high-throughput screening in just a few hours, identifies the ones most desirable for a certain task, and then determines these variants’ DNA sequences.

For example, they used this evolutionary process on a peptide, a small fragment of protein, from the seeds of a plant known as a squirting cucumber to turn the molecule into a favorable drug scaffold. “We ran the protein through this evolution process to create a tumor-targeting protein that we then hooked the chemotherapy agents on to,” said Cochran.

Cochran’s group is also investigating immunotherapy applications for her proteins. She is teaming up with Dane Wittrup, PhD, a professor in chemical engineering and biological engineering at Massachusetts Institute of Technology, who has developed new ways to use the immune system. By combining Cochran’s tumor-targeting technology with Wittrup’s insights into immunotherapy, they are able to give a “one-two punch” and activate multiple factors of the immune system to more effectively attack cancer, she said.

Her research team is also interested in applying their work to other diseases. She explained to Altman:

“We’ve been applying them for cancer, but you can use the same approach to deliver therapies to other types of disease tissue. We have really only just scratched the surface of what we can do. A big driver of this has been the interdisciplinary culture of collaborative research at Stanford. We’ve been working together with physicians, clinicians, scientists, engineers and physicists to tackle really challenging problems.”

Cochran’s bioengineered proteins are not yet available to patients. However, some tumor-targeting molecules are already approved by the U.S. Food and Drug Administration and many more are in the pipeline. “There are a number of molecules that are FDA approved and you might have heard commercials for them,” she told Altman. “But they only work for a subset of patients. So the question is: how do we make them work better for a larger subset of patients?”

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


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