New study observes Tuberculosis bacteria attacking antibiotics

Posted June 8, 2018 by Jennifer Huber
Categories: biology, Health

Tags: , ,

Photograph by torange.biz

Tuberculosis was one of the deadliest known diseases, until antibiotics were discovered and used to dramatically reduce its incidence throughout the world. Unfortunately, before the infectious disease could be eradicated, drug-resistant forms emerged as a major public health threat — one quarter of the world’s population is currently infected with TB and 600,000 people develop drug-resistant TB annually.

New research at SLAC National Accelerator Laboratory is seeking to better understand how this antibiotic resistance develops, as recently reported in BMC Biology.

TB is caused by Mycobacterium tuberculosis bacteria, which attack the lungs and then spread to other parts of the body. The bacteria are transmitted to other people through the air, when an infected person speaks, coughs or sneezes.

These bacteria survive antimicrobial drugs by mutating. Their resilience is enhanced by the lengthy and complex nature of standard treatment, which requires patients to take four drugs every day for six to nine months. Patients often don’t complete this full course of TB treatment, causing the bacteria to evolve to survive the antibiotics.

Now, a team of international researchers has investigated an enzyme, called beta-lactamase, that is produced by the Mycobacterium tuberculosis bacteria. They wanted to understand the critical role this enzyme plays in TB drug resistance.

Specifically, the researchers made tiny crystals of beta-lactamase and mixed them with the antibiotic ceftriaxone. A fraction of a second later, they hit the enzyme-antibiotic mixture with ultrafast, intense X-ray pulses from SLAC’s Linac Coherent Light Source — taking millions of X-ray snapshots of the chemical reaction in real time for two seconds.

Putting these snapshots together, the researchers mapped out the 3D structure of the antibiotic as it interacted with the enzyme. They watched the bacterial enzyme bind to the antibiotic and then break open one of its key chemical bonds, making the antibiotic ineffective.

“For structural biologists, this is how we learn exactly how biology functions,” said Mark Hunter, PhD, staff scientist at SLAC and co-author on the study, in a recent news release. “We decipher a molecule’s structure at a certain point in time, and it gives us a better idea of how the molecule works.”

The research team plans to use their method to study additional antibiotics, observing in real time the rapid molecular processes that occur as the bacteria’s enzymes breakdown the drugs. Ultimately, they hope this knowledge can be used to design better antibiotics that can fight off these attacks.

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

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Assessing our nation’s control of blood pressure: A Q&A

Posted May 31, 2018 by Jennifer Huber
Categories: Health

Tags: ,

Photo by agilemktg1

Whenever you see a physician, an assistant probably takes your blood pressure. But does she tell you what the numbers mean?

The top number, called the systolic blood pressure (SBP), measures the maximum pressure your heart exerts while beating. The bottom number, called the diastolic blood pressure (DBP), measures the amount of pressure in your arteries between beats. Both are important. High systolic and diastolic blood pressure are associated with a higher risk of heart attacks, heart failure, stroke and kidney disease.

But what is considered high enough to treat? I was recently surprised to learn that physicians are still debating the national blood pressure clinical guidelines. To learn more, I spoke with Shreya Shah, MD, a clinical instructor of primary care and population health at Stanford.”

Why have clinical guidelines for blood pressure been controversial?

“Recommendations regarding optimal blood pressure control have shifted over the past decade. In 2003, the recommendations were to target a systolic blood pressure less than 140 for most patients and less than 130 for patients with certain risk factors. In 2014, new recommendations relaxed the blood pressure goals to a SBP less than 140 for most patients and less than 150 for those 60 and above. This was a big change in recommendations and thus sparked controversy.

Newer studies, especially the SPRINT trial, point towards the increased benefits of more intensive blood pressure control. This led to the recent set of guidelines in 2017.

At Stanford, we’re working to bring blood pressures down as close to normal as possible. We are targeting a SBP less than 140 and DBP less than 90 in all patients. But for those with certain risk factors, especially increased risk for heart disease, we may recommend lowering the goal to a SBP less than 130 and DBP less than 80.”

Are these goals being met? What did your latest study find?

“Using a national database, Randall Stafford, MD, and I analyzed patterns of blood pressure control for millions of patients who were treated for hypertension in 2016.

Our study, which appears in the Journal of General Internal Medicine, found that we’re not doing a great job with blood pressure control: 43 percent of hypertension patients had a SBP of 140 or higher and 24 percent of patients had a SBP of 150 or higher.

There were also higher rates of uncontrolled blood pressure among certain demographic groups — blacks, Hispanics and patients with Medicaid. These groups may have had less intensive attention to their high blood pressure for a number of reasons, including less access to high quality care and an inability to afford some medications.”

What can be done?

“Studies have demonstrated that team-based care leads to better improvements in blood pressure when compared to traditional models of primary care. Team-based care for hypertension involves the patient and their primary care physician, as well as other health professionals such as pharmacists, nurses, dieticians, case managers and social workers. Especially for treatment strategies involving health behavior change, physicians may not be as effective as other people whose training focused on these skills.

Stanford has already implemented this team-based care model in our primary-care clinics. And we are looking at other strategies, including helping our patients to be more involved in managing their high blood pressure. For instance, I encourage patients to regularly measure their blood pressure at home. The American Heart Association has resources available with information about choosing a home blood pressure monitor and using the correct home blood pressure technique.

I also encourage my patients to adopt a largely plant-based diet, lose weight and become more physically active. These non-medication strategies can be helpful for preventing high blood pressure, but are also as an integral part of treating high blood pressure.”

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

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

Posted May 9, 2018 by Jennifer Huber
Categories: biology, Health

Tags: ,

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.

On caring for suicidal patients: A psychiatrist reflects

Posted April 26, 2018 by Jennifer Huber
Categories: Health

Tags: , ,

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

Posted April 23, 2018 by Jennifer Huber
Categories: Health

Tags: ,

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

Posted April 20, 2018 by Jennifer Huber
Categories: Health

Tags: , , ,

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

Posted April 18, 2018 by Jennifer Huber
Categories: Health

Tags: , ,

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.


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