Archive for the ‘Health’ category

Drug blocks Zika and other deadly viruses in cells cultures, Stanford study finds

December 12, 2017

Photo of Jan Carette by Paul Sakuma

A team of Stanford researchers is developing approaches to thwart a family of deadly viruses, called flaviviruses, by targeting the human cells that host these invading pathogens.

Flaviviruses include the dengue-fever, yellow-fever, West Nile and Zika viruses transmitted to humans by mosquitoes, as well as encephalitis transmitted by ticks. Unfortunately, approved antiviral drugs for these diseases aren’t currently available.

So, instead of the traditional approach of attacking an individual virus directly, the researchers focused on the cellular factors of their human hosts that are essential to many viral infections.

“Generally, when you develop a drug against a specific protein in dengue virus, for instance, it won’t work for yellow fever or Zika, and you have to develop new antivirals for each,” said Stanford virologist Jan Carette, PhD, in a recent Stanford news release. “Here, by targeting the host rather than a specific virus, we’ve been able to take out multiple viruses at once.”

Earlier, the team genetically profiled human cells to identity the host factors necessary for the viruses to replicate inside the cells — revealing new candidate targets for antiviral drug development. Specifically, they demonstrated the importance of the oligosaccharyltransferase (OST) complex that attaches sugar molecules to proteins. They found flaviviruses did not infect their genetically engineered cells without OST.

In the new study, recently published in Cell Reports, the Stanford researchers collaborated with scientists at Yale University to test the effectiveness of a drug called NGI-1, which inhibits the activity of the OST complex.

They showed that low concentrations of NGI-1 could be used to block the viruses from replicating without harming the host cells — successfully reducing the infection by 99 percent when treating cells immediately after they were infected by Zika or dengue virus, and by 80 percent when administered 24 hours after infection.

Their study also indicated that the viruses are unlikely to become resistant to NGI-1. “When you target a host function rather than a viral protein, it’s usually much more difficult for a virus to develop resistance,” Carette said in the release.

The researchers are now busy with follow-up studies to test NGI-1 in small animal models of dengue fever and are also developing similar drugs with improved specificity.

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

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Researchers investigate fruit flies as a step towards understanding the human brain

December 7, 2017

Photo by nuzree

Researchers have been trying to map out the brain’s complex neural circuits to understand how diseases like Parkinson’s disrupt healthy brain communication, in hopes of designing better therapies.

That, obviously, is not easy. So a Stanford research team led by biology professor Liqun Luo, PhD, and bioengineer and physicist Stephen Quake, PhD, are instead studying fruit fly brains — yes, those pesky bugs that fly around your bananas.

Specifically, they have mapped out a blueprint for the fruit fly’s olfactory neurons — identifying how specific gene and protein activity correlates with the biological circuitry of different neuronal cell types. The researchers focused on a fruit fly’s sense of smell because the function, physiology and anatomy of its olfactory system are well known, making it a simple and ideal test bed for their research.

They measured the gene expression profiles using a single-cell sequencing technology developed for mice and human cell types, which they modified to work for the smaller and simpler fruit fly cells.

The team determined different types of neurons express genes differently during development, but gene expression between the neuron types becomes indistinguishable as the flies mature, as recently reported in Cell.

“Once the brain is wired up, the fly doesn’t need to express those genes that help them in choosing the connection partners,” said first author and Stanford biology postdoc Hongjie Li, PhD, in a recent news release. “So there is less gene expression in the adult flies.”

The researchers are a long way from using their technique to map the human brain, but they aren’t daunted by the challeng. “By further developing this approach, we hope to one day reverse-engineer and perhaps even repair defective circuitry in the human brain,” Li said in the release.

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

Stanford undergraduates tackle health inequity in the emergency room

November 29, 2017

Photo by Sloane Maples of SHARED volunteers Nathan Pan-Doh, Josh Bloomstein and Kyle Lin

When I think of the emergency department, I think of patients in crisis from a heart attack, traumatic injury, overdose or other medical emergencies. However, physicians are now recognizing that the underlying drivers of these health crises are social, economic, political and structural inequalities that physicians can’t solve alone.

In order to help reduce health inequity, Jennifer Newberry, MD, JD, a clinical assistant professor in emergency medicine at Stanford, started Stanford Health Advocacy and Research in the Emergency Department, or SHARED. SHARED provides an opportunity for Stanford undergraduates to screen patients and connect them to local resources and programs.

SHARED consists of two programs. It started in 2012 with the Stanford Alcohol Screening and Brief Intervention program, which aims to identify and reduce high-risk alcohol use. Stanford undergraduate volunteers administer electronic screening questionnaires and provide patients with information on alcohol safety, and then high-risk patients are able to meet briefly with a social worker.

SHARED then expanded to develop the Help Desk, which screens emergency department patients for social and legal needs — such as problems with health insurance, food insecurity, homelessness and employment. The undergraduate team identifies patients’ unmet needs, eligibility of support and the appropriate community resources during the ER visit. They also follow up by calling the patients every two weeks to provide further assistance with accessing resources.

“So many patients and families carry the stress and anxiety of food insecurity, impending evictions, or even potential deportations, without anyone to hear their story. Our students listen and provide compassionate support amidst the chaos of an emergency department,” Newberry said.

Volunteer Josh Bloomstein said he joined SHARED in 2016 to make a difference in the lives of underserved patients.

Bloomstein’s Spanish skills have come in handy at the Help Desk during his two-hour shifts twice per week. For instance, he told me about his experience with an uninsured Spanish-speaking patient:

The patient was concerned that I was working with the billing department and was also hesitant to answer questions about immigration. I assured her that the purpose of the Help Desk is to assist patients with social needs and that all topics remain confidential. Together we found a primary care physician and a dentist who offered discounted services near her home. She was also grateful for the information we provided her on Covered California insurance, JobTrain skills training classes and the immigration advocacy organization Libre.

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

Digital divide for electronic health records worth investigating, researcher says

November 15, 2017

Photo by mcmurryjulie

Over the past several years, most hospitals have adopted electronic health records — a digital version of a patient’s medical chart that can contain information from all clinicians involved in a patient’s care. The goal is to provide better, more coordinated care through EHRs, although they are also increasingly cited as a source of physician burnout.

But there may be another problem with the implementation of EHR systems: although EHR adoption is widespread, the use of the records varies at different hospitals. According to a recent presentation at the 2017 American Medical Informatics Association’s annual meeting, hospitals with fewer resources are less likely to use the advanced functionality of EHRs for measuring performance and engaging patients.

The University of Michigan researchers analyzed data from almost 3000 medical-surgical acute care hospitals in the United States, based on the 2008 to 2015 American Hospital Association Annual and IT Supplement surveys.

First, they evaluated which hospitals have adopted “basic” verses “comprehensive” EHR functions. They found larger, urban hospitals participating in payment reforms were far more likely to use a comprehensive system than small, rural and safety-net hospitals — creating a digital “use” divide of EHRs.

Next, the researchers analyzed questions newly available on the 2015 Supplement to further assess hospital use of EHRs for 10 performance measurement and patient engagement functions. Over all hospitals, the most commonly adopted performance measurement functions were used to monitor patient safety and create dashboards of individual provider performance. Similarly, the most common patient engagement function allowed patients to view data online and download it.

However, critical access hospitals overall were less likely to have adopted eight or more of the ten EHR functions of either category.

The conference speaker Julie Adler-Milstein, PhD, was an associate professor at the University of Michigan during this research and is now at the University of California, San Francisco Medical Center. She said she is concerned about this emerging divide because these advanced EHR functions are essential for improving hospital performance. “We do need to consider what we can be doing to help safety-net hospitals make sure that they are able to continue their adoption trajectory and invest in some of these more substantive and important capabilities,” said Adler-Milstein in a recent news piece.

Specifically, the authors recommended in the abstract that policymakers drive greater EHR adoption using direct funding for health IT and indirect incentives to promote value-based payment and delivery models. They concluded, “Policymakers may need to consider specific actions to target safety-net hospitals, which could include funding as well as technical assistance with implementation.”

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

Researchers investigate new treatment for glaucoma

November 13, 2017

As an avid reader, I find I can get through just about anything if I can decompress and escape into a good book — so the idea of losing my vision is scary. However, millions of Americans face this fear due to glaucoma, a leading cause of blindness for those over 60.

Now, vision scientists at the University of California, Berkeley have discovered a new target for treating glaucoma, as recently reported in the Journal of Clinical Investigation.

Glaucoma is a neurodegenerative disease of the major nerve of vision, called the optic nerve. Typically, fluid builds up in the front part of the eye, causing pressure that irreversibly damages the optic nerve. If left untreated, glaucoma can lead to vision loss and permanent blindness.

Current treatments focus on lowering eye pressure using eye drops, oral medications, laser therapy or surgery. But researchers are searching for a way to prevent or stop the neurodegeneration itself. Berkeley researchers have now identified a new mechanism for stopping this degeneration in rats and mice with glaucoma.

Their research focused on the role of retinal astrocytes — cells that help make up the nerve fiber layer of the retina and optic nerve — which are important for developing and maintaining healthy eyes. They discovered that retinal astrocytes release powerful molecules called lipoxins A4 and B4 that act locally to dampen inflammation and help coordinate protective signaling for neurons in the eye. Surprisingly, they determined that astrocytes produce less of these lipoxins in eyes affected by glaucoma.

“Our research discovered that astrocytes that are triggered by injury actually turn off novel neuroprotective signals that prevent optic nerve damage,” explained study senior author John Flanagan, OD, PhD, professor and dean of optometry at UC Berkeley, in a recent news release.

The research team then tested the most promising lipoxin B4 as a therapy. Rodents were treated with lipoxin B4 eight weeks after developing glaucoma-like effects — the critical time point when the neurodegeneration typically becomes irreversible. After 15 weeks, they found that lipoxin B4 stopped the cells’ neurodegeneration.

Based on these encouraging results, the Berkeley researchers plan to further explore the therapeutic potential of these lipoxins for glaucoma and other neurodegenerative diseases, such as Alzheimer’s and Parkinson’s.

“These naturally occurring small lipids have great potential as therapies because they may play a fundamental role in preventing other neurodegenerative diseases. And that’s hugely significant,” said Flanagan in the release.

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

Educating the next generation of surgeons: A Q&A

November 9, 2017

Photo by Rachel Baker

Research shows that many medical students view surgeons as intimidating, competitive and predominantly male workaholics — and these stereotypes can deter students from a surgical career. As a result, there has been a relative drop in applications for surgical residencies.

James Lau, MD, a clinical professor of surgery and the director of the Goodman Surgical Educational Center at Stanford, is working to combat this trend by spearheading educational initiatives. I caught up with him recently.

Why is there a declining interest in surgical careers?

“Medical students are becoming more sophisticated in choosing specialties, and a lot likely has to do with life style issues. I think there’s a misconception that surgeons work all the time and can’t have a work-life balance.

Medical schools are also getting shorter — some are even going to three years and some schools are emphasizing primary care — so students aren’t exposed early on to surgery. So we’ve built a mentorship component into our SURG 205 surgical training course to give first- and second-year medical students at Stanford the opportunity to go into the operating room and learn what surgery is like. And it sparks the flame and shows them more accurately the collegiality and dedication of those in surgery.”

What do your students learn in SURG 205?

“Previously the students would have to find a mentor and negotiate the system on their own to get the training to be allowed in the operating room. This course brings it all together —training them on technical skills, facilitating finding them a mentor, experiencing one or two operations and hopefully building an ongoing mentor relationship with an attending surgeon.

We want them to participate in the OR, so we train them on technical skills — from the simple skills like knot-tying and basic suturing to performing a full case on a cadaver. As we explained in a recent paper, we also teach them nontechnical skills, such as coaching them on how to get along with the operating team, so they feel more comfortable when they go to the OR.”

What other educational efforts are underway?

“Surgery residents and surgeons have to know more than technical skills to do operations. They also have to work well together in teams in different settings. They have to be able to interact well with patients and make clinical decisions. And the techniques are changing all the time. So we provide a skills and simulation center with a curriculum — to help teach and mentor these skills.

We also must train inter-professionally in surgery. The nurses, anesthesiologists and surgeons all work together but traditionally train separately, which makes no sense. In a new program, we’re having monthly simulations in the operating room with surgeons, surgery residents, anesthesiologists, anesthesiology residents, OR assistants, scrub technicians, circulating nurses, and anyone else that would normally be in the operating room. We want people to understand that everyone has a role and should speak up in crisis. We’re trying to change the culture by training together.

We also have a resident as educator program, because our residents are automatically teachers and mentors to the medical students. To be a good teacher, you have to be a constant learner and create a safe learning environment. A good teacher is a good communicator and their learners include the patients.”

Why did you recently get a Master’s Degree in Health Professions Education?

“I oversee a two-year surgical education fellowship that has surgery residents teach, create curricula and evaluate the work that they do in the clerkships and residency education programs here at Stanford. Our goal is to prepare them to be thoughtful program directors, helping to make them the next generation’s education leaders in surgery. As part of the program, we encourage them to complete a master’s degree in education. To be a mentor for them, I decided to ‘walk the walk’ and get a masters degree in education. After a decade in education, I wanted to inform myself in the formal discipline of education to become more effective in the programs that we create for learners here at Stanford.”

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

Stanford researchers grow neural stem cells more efficiently in 3-D gel

November 7, 2017

Photo by luismmolina/Getty Images

Stem cells have the potential to help us understand and treat a range of diseases and injuries — from vision loss to cancers. For instance, a Japanese man in his 60s was recently treated for vision loss due to macular degeneration using stem cells donated by another person. And many other clinical trials involving stem cells are underway.

However, there is still a lot to learn about stem cells and many barriers to overcome before most potential treatments can be realized. One such barrier is how to grow large quantities of stem cells while maintaining their unique properties. Now, Stanford researchers have developed a new gel in which they can grow massive numbers of neural stem cells in less space.

Stem cells are unspecialized cells that can self-renew and develop into many different types of cells in the body. Researchers hope that neural stem cells — that differentiate into neurons and glia cells in the nervous system — can be used to treat spinal cord injuries, Parkinson disease, Huntington disease and other nervous system disorders.

As recently reported in Nature Materials, the Stanford team engineered a new polymer-based gel optimized for neural stem cells, growing them in three dimensions instead of two.

“For a 3-D culture, we need only a 4-inch-by-4-inch plot of lab space, or about 16 square inches. A 2-D culture requires a plot of four feet by four feet, or about 16 square feet,” said the study’s first author Chris Madl, PhD, a postdoctoral research fellow in microbiology and immunology at Stanford, in a recent Stanford news release. In addition to taking 100-times less lab space, the new 3-D process also demands less energy and nutrients to grow the cells, he said.

A key to the development was the realization that neural stem cells need to chemically or physically remodel their surrounding environment to maintain their ability to differentiate into other cells. The researchers discovered this by creating and testing a family of gels with varying stiffness and remodeling susceptibilities. The authors explained in the paper, “Whereas cells cultured in 2-D are unrestricted and free to spread, cells within nanoporous 3-D hydrogels require matrix remodeling to spread, migrate, and proliferate.”

Surprisingly, they also discovered that the neural stem cells weren’t sensitive to the stiffness of the gel, unlike most other stem cells.

These new findings have given the leader of the research group new hope for future stem cell therapies. Sarah Heilshorn, PhD, associate professor of materials science and engineering at Stanford, said in the release, “There’s this convergence of biological knowledge and engineering principles in stem cell research that has me hopeful we might finally actually solve big problems.”

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


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