Archive for the ‘Health’ category

New understanding of cellular signaling could help design better drugs, Stanford study finds

May 9, 2018

An effective drug with minimal side effects — the dream of all drug companies, physicians and patients. But is it an impossible dream?

Perhaps not, in light of new research led by Ron Dror, PhD, an associate professor of computer science at Stanford. IN collaboration with other researchers, Dror used computer simulations and lab experiments to better understand G-protein-coupled receptors, which are critical to drug development.

G-protein-coupled receptors (GPCRs) are involved in an incredible array of physiological processes in the human body, including vision, taste, smell, mood regulation and pain, to name just a few. As a result, GPCRs are the primary target for drugs — about 34 percent of all prescription pharmaceuticals currently on the market target them. Unfortunately, despite all of this drug research, many of the underlying mechanisms of how GPCRs function are still unclear.

We do know that GPCRs act like an inbox for biochemical messages, which alert the cells that nutrients are nearby or communicate information sent by other cells. These messages symbolize a variety of signaling or pharmaceutical molecules. When one of these molecules binds to a GPCR, the GPCR changes shape — triggering many molecular changes within the cell.

Dror’s team investigated the relationship between these GPCRs and a key family of molecules inside cells called arrestins, which can be activated by GPCRs and can lead to unanticipated side effects from medications. Specifically, they sought to understand how GPCRs activate arrestin, so they can use this knowledge in the future to design drugs with fewer side effects.

“We want the good without the bad — more effective drugs with fewer dangerous side effects,” Dror said in a recent Stanford news release. “For GPCRs, that often boils down to whether or not the drug causes the GPCR to stimulate arrestin.”

Researchers know that GPCR is composed of a long tail and a rounder core, which bind to distinct locations on the arrestin molecule. Based on past studies, it was believed that only the receptor’s tail activated the arrestin — causing it to change shape and begin signaling other molecules on its own.

However, Dror’s new study demonstrated that either the tail or core can activate arrestin, as recently reported in Nature. And the core and tail together can activate the arrestin even more, Dror said.

Using this new understanding, the researchers hope in the future to design drugs that activate arrestin in a more selective way to reduce drug side effects.

Dror concluded in the release:

“These behaviors are critical to drug effects, and this should help us in the next phase of our research as we try to learn more about the interplay of GPCRs and arrestins, and potentially, new drugs.”

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

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On caring for suicidal patients: A psychiatrist reflects

April 26, 2018

Photo by Counseling

Many hospital psychiatrists work in emergency rooms, psychiatric wards and intensive care units where they treat patients who have intentionally harmed themselves. Stanford psychiatry resident Nathaniel P. Morris, MD, writes about his experiences caring for suicidal patients in a recent opinion piece in JAMA.

Depression, psychosis, substance abuse, post-traumatic stress disorder or other psychiatric illnesses can drive individuals to cause themselves severe physical harm, he writes..

Once life saving measures are taken, hospital psychiatrists are called whenever self-inflicted injuries are suspected. “We play a part in stabilizing patients, from evaluating whether patients need involuntary commitment, to managing agitation, to reviewing patients’ home psychiatric medications,” Morris says. But at the core, psychiatrists try to figure out why the patients hurt themselves, he adds.

While caring for these deeply ill patients, psychiatrists need to manage their own emotions, Morris says. In the piece, he depicts what it feels like when he walks into the rooms of suicidal patients, having to hide his reaction to their shocking injuries and, following the advice of a senior physician, “act like he’s seen worse.”

He also admits his concern over releasing patients once they are doing better:

“Yet I always have a sinking feeling as discharge dates approach. I worry about what will happen when my patients leave the controlled environment of the hospital… I try to accept that I cannot control my patients’ fates. But their stories stay with me. When I leave the hospital, I often find myself scanning the faces around me, looking for the ones seared into my memory, hoping to see that my patients are okay.”

It is work he never completely leaves behind, Morris confesses. His experiences offer him a closeup look, albeit a pain-filled one, into the lives of the mentally ill.

So Morris hopes to spread awareness of the harm caused by depression and other psychiatric issues, explaining in the piece:

“Americans worry that people with mental illness will hurt others, but we don’t talk enough about the horrors that distressed people inflict on themselves.”

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

Advice on how to cope with the threat of school shootings

April 23, 2018

Like older adults who grew up with the imminent threat of nuclear bombs during the cold war, children are now growing up with mass shootings — the new normal.

Since the Columbine massacre in 1999, kids began participating in school lockdown and active-shooter drills. Some also face metal detectors, bulletproof Shelter-In-Place bunkers and other security measures in their schools. Classrooms no longer seem like a safe place and this stress may be impacting our children’s long-term health and development.

Victor Carrion, MD, a professor of psychiatry and behavioral sciences at Stanford, studies the interplay between brain development and stress vulnerability. In a recent Stanford Magazine article, he offers some advice on how families can cope with the stress of school safety:

  • Parents should proactively talk with their child about difficult topics in a developmentally sensitive way.
  • If parents are worried about their child’s stress level, they should look for a change in function. Very young children can become clingier. Older kids often convert depression or anxiety into physical symptoms like a stomach ache or headache. And adolescents frequently withdraw.
  • School drills should include three steps: a school orientation about the drill, the actual drill practice, and a follow-up discussion to help children process how they felt during the exercise.
  • School administrators, teachers, parents, police and the community need to work together to create an environment where the child feels safe, secure and protected.

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

Community cooperation following disasters key to recovery, Stanford study finds

April 20, 2018

Photo of Norway by Vidar Nordli-Mathisen

Why are some communities resilient in the face of disasters such as epidemics, while others struggle to recover? You might think it is driven by the availability of economic resources, but a new study shows that community cooperation — admittedly challenging in the face of an infectious disease — is the key.

Recently published in Academy of Management Journal, the study led by Hayagreeva Rao, PhD, a Stanford Business professor, found that a community’s resilience primarily depends on two factors:

  • whether the cause of the disaster is attributed to other community members or an act of nature; and
  • whether the community includes diverse organizations that encourage collaboration.

The researchers analyzed and compared two well-documented disasters that occurred in Norway in the early 1900s: an outbreak of the highly-contagious Spanish flu that caused many fatalities, and a severe spring frost that led to economic hardship for the predominantly farming community.

They found that disasters attributed to other community members — like contagious epidemics — weakened cooperation, increased distrust and led to a long-term reduction in organization building. By contrast, disasters attributed to an act of nature evoked a sense of shared fate that fostered cooperation.

Rao and colleague Henrich Greve, PhD, a professor of entrepreneurship at INSEAD, explained in the paper:

“The typical response to pandemics includes isolation and treatment, home quarantines, closure of schools, cancellation of large-scale public meetings, and other steps to reduce social density. While these immediate responses are entirely practical, policy planners should also consider how a pandemic impairs the social infrastructure of a community over the long term, and undertake initiatives to foster the building of community organizations.”

For instance, the Spanish flu impaired the Norwegian communities from building new community organizations for 25 years, they wrote.

In contrast, Norway’s farming families pulled together when faced with natural agricultural disasters — motivating them to form retail cooperatives, mutual insurance organizations and savings banks to help share risk.

The researchers determined that successful disaster recovery also hinged on the existing social infrastructure: a community with diverse and cooperative voluntary organizations more effectively responded.

“The better the infrastructure, the better the recovery,” said Rao in a recent Stanford Business news piece. “A disaster is a shock. Think of those organizations as the shock absorbers.”

In the paper, they offered an example. In the 1995 heat wave in Chicago, which led to far fewer deaths in a Latino neighborhood than in an adjacent African-American neighborhood. This was because the sheer variety of Latino neighborhood organizations created overlapping networks that allowed people to check on the elderly, they wrote.

The authors concluded with a call for more research on the effect of climate-related disasters like floods and droughts. We need to know how these impact the birth and sustainability of community volunteer organizations, they said.

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

Dentistry in the hospital: A Q&A

April 18, 2018

Photo of Dyani Gaudilliere (right) in OR; by Vladimir Nekhendzy

In the U.S., medicine and dentistry are separate — they typically have different insurance systems, training regimes and workplaces. So I was intrigued when I heard about hospital dentists. To learn more about what they do, I spoke with Dyani Gaudilliere, DMD, a clinical assistant professor of surgery and chief of the dental section at Stanford.

Why did you choose to combine dentistry with medicine?

“I started on the path towards dentistry in my teens, planning to become an orthodontist. I became increasingly interested in public health, with the goal of treating underserved populations.

At my dental school (Harvard), the dental and medical school courses were combined for the first two years with the goal of fostering a more integrated approach to dentistry, which prepared me well for my current work.

The split between medicine and dentistry is, in fact, completely artificial. The bacterial diseases of the teeth and gingiva affect the entire immune system and can cause serious systemic consequences. In addition, many systemic diseases and medications have oral manifestations.”

What do you do at Stanford?

“The majority of our patients at Stanford are being treated for cancer, organ transplantation, cardiac disease or joint replacement. Our goal is to rid these patients of bacterial disease in their teeth and gums prior to their treatments. It may be risky to treat them outside the hospital, without access to the their full medical records or emergency services. Lack of dental insurance can also be a barrier for patients whose chronic disease prevents them from being employed.”

Can you tell me more about your patients?

“One large category of patients we see are those with cancer of the head and neck. Targeted radiation to this area and chemotherapy have serious long-term side effects, ranging from dry mouth resulting in rampant tooth decay to severe jaw infections. For this reason, we perform dental examination and patient education prior to these treatments. We also partner with the head and neck surgeons to remove infected teeth during their cancer resection surgery. And we create special oral positioning devices to aid the radiation oncologists in spacing and immobilizing the tissues during radiation therapy.

We also see patients before medical treatments that will leave them immunocompromised, such as chemotherapy or organ transplantation. Chronic tooth or gum infections can suddenly become life threatening in a patient who is immunocompromised.

A third example is trauma. It is common for patients to get in minor bike accidents and fly right over their handlebars onto their teeth. We see these patients in the emergency department urgently in order to put the teeth and supporting bone back into place and then stabilize them with cemented splints.”

Are there many hospital dentists?

“I believe there isn’t enough awareness of the medical necessity of dental care, nor are there enough hospital dentists. Some hospitals are lucky to be affiliated with dental schools, whereas most have no in-house or emergency dental team at all. We regularly receive patients transferred from outside hospitals with large infections or oral trauma, because these hospitals didn’t have anybody with the right expertise to treat the conditions.

There are a lot of barriers we need to cross in order to fully integrate dentistry and medicine, but I think this integration is way overdue.”

What is your view on the separation between dentistry and medicine?

“The reason for the separation seems to be a combination of history and politics. Tooth extractions and other surgeries were historically performed by barber-surgeons rather than physicians, and oral care developed as a separate track from care of literally every other part of the body. Fast forward to today and you have dentists lobbying to sustain this separation in order to spare their profession from the regulations and changes occurring in the medical care world.

The idea that dentists would not need medical knowledge is laughable considering how much surgery they perform. Dentists who don’t understand medications and their mechanisms would not last long after their patient on blood thinners loses pints of blood after an extraction.”

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

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

April 12, 2018

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.

New way to understand tumor diversity combines CRISPR with genetic barcodes

April 10, 2018

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.


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