Every year, in the interim between the last bites of my Thanksgiving meal and my first cup of coffee on Black Friday, a gnawing uneasiness begins in the pit of my stomach. The holiday season has now, undeniably, begun and it’s time to start the mental Jenga that is arranging my vacation travel so I can visit multiple families in different states.

I know a perfect holiday with each family isn’t possible. I also understand that I’ll burn myself out if I try to please everyone. Yet, every year, I struggle to put this knowledge into practice.

So, to bolster my resolve to have a healthier holiday, I did some research on the topic and found this post by BeWell @Stanford. In the Q&A, marriage and family therapist Mary Foston-English, explains that the holidays are hard for many people because they’re often coupled with uncomfortable situations, reminders of a lost loved one or unpleasant memories. She also describes how unrealistic expectations can can contribute to holiday stress. We may think:

• “Holidays are supposed to be joyous and happy.”
• “Holidays are times when families come together.”
• “If you don’t have family, then there’s no reason to celebrate.”
• “There’s no place like home for the holidays.”
• “The bigger the gift and/or the more we spend, the better.”
• “Everything has to be perfect.”

And we couldn’t be more wrong.

Foston-English offers several sanity-saving tips on how to communicate better with our families, how to deal with ‘that’ relative and how to avoid overextending ourselves emotionally, financially and emotionally. Here are a few of Foston-English’s nuggets of wisdom:

• Have realistic expectations of yourself and others.
• Become aware of how unhappy/traumatic memories impact the holidays. If you associate the holidays with unhappy times, then the holidays can bring it all back.
• Try to accept family members and friends as they are, even if they don’t live up to all of your expectations. It’s not a good idea to use the holidays to “confront.”
• Establish “healthy” boundaries for yourself: It’s OK to say “no.”

I highly recommend reading and sharing the article. Here’s to a healthier holiday season for all of us.

Previously: Health psychologist responds to questions on coping with holiday stress and Ask Stanford Med: David Spiegel answers your questions on holiday stress and depression
Photo by eren {sea+prairie}

Start talking with physician-scientist Ami Bhatt, MD, PhD, about the microbiome — the vast community of bacteria, fungi, and life that live on the body — and she’ll discuss the potential of these dynamic microscopic ecosystems with such contagious enthusiasm and clarity that you’ll find yourself nodding alongside her, agreeing with her every point.

Bhatt is intensely curious, a trait she’s had since childhood, and deeply committed to the idea of using science to help others. These dual instincts initially led her to medicine, where she found her calling as a physician-scientist.

I feel like I am one of those lucky few who get to do exactly what they want to do.

Today Bhatt runs her own laboratory at Stanford, where she studies how shifts in the microbiome affect human disease and patient outcomes.

“The fundamental thesis that drives our research,” Bhatt explained in a recently published piece on the Department of Medicine website, “is that patient outcomes are manipulated or modified by the alterations in their microbiota, and that we can discover these microbes using sequence-based technologies.”

Another of Bhatt’s initiatives aims to unravel a particularly interesting—and timely—question: What molecular changes occur during a fecal microbiota transfer? To answer this, Bhatt and her colleagues have developed a computational pipeline that will provide a time-based characterization of what actually happens during a transfer.

While her research goals are ambitious and varied, the source of Bhatt’s passion remains the same. “I’m still committed to the idea of being able to help people using science,” she said. “I feel like I am one of those lucky few who get to do exactly what they want to do.”

Previously: At TEDMED 2015: How microbiome studies could improve the future of humanity, Investigating the human microbiome: “We’re only just beginning and there is so much more to explore” and Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease
Photo by Norbert von der Groeben

With the parents gone away, the children have time to play — and eat, according to new research that examines the health of the millions of Chinese children left with families when their parents move to urban centers.

Researchers from the University of Manchester in England analyzed the dietary choices of 975 children from 140 rural villages. Led by graduate student Nan Zhang, the team found children living with their grandparents or a single parent ate more fat and less protein than children living with two parents. The research appeared in Public Health Nutrition.

The diets of boys particularly worsened, a finding that has complex implications in a society where males are favored, Zhang said in a news release.

The study did not examine why the childrens’ diets changed, but Zhang has several theories. From the release:

The researchers speculate that mothers moving away from home generally earn less, and that these lower earnings act in combination with grandparents’ poorer dietary knowledge or willingness to spend more on food…

Another factor at work could be that prices of protein-based foods such as eggs and meat have increased faster than many households’ incomes.

The study highlights the need for increased public education on nutrition, she said.

Previously: Building the case for a national hepatitis B treatment program in China, Seeking solutions to childhood anemia in China and  “We should act now”: Stanford expert calls for more targeted anti-obesity policies
Photo by T Chu

Coffee changes the brain’s activity. Wait, wait, don’t stop reading, I know you know that. But here’s the cool thing: For 18 months, Stanford psychologist Russell Poldrack, PhD, scanned his brain twice a week. On the days he skipped coffee, the MRI images were quite different, showing, for the first time, how caffeine changes brain connectivity.

A Stanford news release explains:

The connection between the somatosensory motor network and the systems responsible for higher vision grew significantly tighter without caffeine.

“That was totally unexpected, but it shows that being caffeinated radically changes the connectivity of your brain,” Poldrack said. “We don’t really know if it’s better or worse, but it’s interesting that these are relatively low-level areas. It may well be that I’m more fatigued on those days, and that drives the brain into this state that’s focused on integrating those basic processes more.”

Poldrack’s experiment could generate hundreds, or even thousands, of similar insights, once researchers parse through the data, which is open to all. The RNA from his white blood cells was also sequenced once a week to coordinate gene expression with brain function.

Poldrack’s brain remained fairly constant and he admits he’s an even-keeled guy, generally content and rarely sad. But he hopes the approach could reveal differences between healthy brains, like his, and those that suffer from schizophrenia or bipolar disorder.

Previously: Hidden memories: A bit of coaching allows subjects to cloack memories from fMRI detector, Image of the Week: Art inspired by MRI brain scans and From phrenology to neuroimaging: New finding bolsters theory about how brain operates

It’s a kick to consider that a part of the brain could act like a radio, with different stations operating at different frequencies, playing different kinds of music and variously attracting or repelling different “listening audiences.” A new study by Stanford neuroscientist Jin Hyung Lee, PhD, and her colleagues has isolated a brain circuit linking just such a “transmission station” in the midbrain to various “listener” regions in the forebrain.

The findings have clear therapeutic potential. In a news release about the research, I wrote:

In a case study published in 2007, [researchers] demonstrated that electrically stimulating the central portion of the thalamus — a deep-brain relay station routing inputs from the senses to myriad cognitive-processing centers throughout the cerebral cortex — could restore consciousness in a patient who’d been in a minimally conscious state for six years.

“But there was no way to know how it worked,” Lee told me.

Now, in a set of experiments published in eLife, she and her associates have used precisely targeted stimulation and recording techniques to show that forcing a set of nerve cells in the central thalamus to fire at 40 or 100 times a minute induces a state of arousal: Rats that were fast asleep wake up and start roving around and exploring their environments. Switch the same nerve cells to a firing frequency of 10 times a minute, and the same rats immediately go into a state of deep unconsciousness more akin to a coma or a petit mal seizure (a transient state of behavioral arrest) than to restful sleep.

In addition to these behavioral effects, forcing those central-thalamic nerve cells to fire at different rates causes distinct structures elsewhere in the brain to rev up or slack off. In a sense, firing at 100 times a minute was like blasting heavy-metal music – some forebrain regions leapt into the mosh pit, some ran for cover – while 10 times a minute (the easy-listenin’ channel?) variously appealed to or turned off different brain areas.

You can’t do that with a drug.

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Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative biomedical researchers.

The enthusiasm of Tom Wandless, PhD, in this video is contagious. Wandless, a professor of chemical and systems biology, injects vigor into the science of protein folding.

Just as in a factory assembly line, sometimes cells produce blooper proteins. And that’s no good: These abnormal proteins can lead to diseases such as Parkinson’s or Huntington’s diseases, Wandless said.

Wandless and his team are currently working to understand how cells distinguish correct from incorrect proteins. “How the cell uses quality control machinery to recognize and ultimately degrade these proteins is a very important question, not only for basic sciences, but ultimately for disease as well,” Wandless says in the video above.

Making inroads on diseases like Parkinson’s alone would be quite an accomplishment, he says. “But what has excited me even more is the potential for understanding the role of protein degredation in disease we don’t even understand yet.”

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Decoding proteins using your very own super computer, Nobel winner Michael Levitt’s animates biological processes and Packed and ready to go: The link between DNA folding and disease

What does it mean to be healthy? This is an important question for the numerous laboratories and hospitals worldwide who dedicate their livelihoods to defeating disease. Thanks to breakthroughs in biotechnology, researchers are starting to develop a more thorough profile of health – and to realize how different it can be from person to person. “We should all go get our ‘healthy’ profiles now before we get sick,” insists Michael Snyder, PhD, professor and chair of Stanford’s Department of Genetics.

Understanding what health means at an individual, molecular, and systematic level was the focus of the recent Personalised Health Conference at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. Notably, the conference served as the kickoff event for the EMBL-Stanford Life Science Alliance and was the first of many anticipated joint conferences. In a preview of the interdisciplinary collaborations the alliance will enable, the four-day conference brought together international experts in genomics, healthcare, bioethics, bioinformatics, cancer, and more.

“The technologies now at our disposal are ushering in a change in the state of medicine, from reactive to proactive, from treating disease to maintaining health,” said Lars Steinmetz, PhD, the conference’s main organizer, in his opening remarks. Steinmetz is spearheading the EMBL-Stanford Life Science Alliance, inspired by his dual affiliation: At Stanford, he is co-director of the Stanford Genome Technology Center (SGTC); at EMBL, he is associate head of the Genome Biology Unit.

The conference was kicked off with a keynote lecture from Leroy Hood, MD, PhD, president and co-founder of the Institute for Systems Biology, who is widely known as the father of personalized medicine. In addition to his vision for systems medicine, Hood presented the 100K Wellness Project, a longitudinal, multiparametric study that generates “dynamical data clouds” for 100,000 healthy individuals.

“By studying the earliest wellness to disease transitions, we aim to enable the earliest reversal of disease back to wellness,” said Hood. “Understanding wellness will allow individuals to reach their full health potential. I predict that a major scientific wellness industry will emerge to play a dominant role in the democratization of health care.”

Hood’s vision was supported by several research efforts presented at the conference. Snyder’s integrative personal omics profiling (iPOP) protocol here at Stanford now measures billions of molecular parameters in several individuals over time, in efforts to develop predictive models of disease that integrate genomic, molecular, environmental, and physiological datasets. Genomics England’s Tim Hubbard, PhD, presented the United Kingdom’s 100,000 Genomes Project, which aims to leverage genome sequence data in the treatment of 100,000 people in the national healthcare system with unmet clinical needs. As the largest national project of its kind, it will help to establish principles and frameworks for incorporating genomics into standard clinical care.

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Next spring, the School of Medicine and Graduate School of Business here will team up to offer a new, one-week residential program for health-care executives. Called “The Innovative Health Care Leader: From Design Thinking to Personal Leadership,” the program will be led by Sarah Soule, PhD, co-director of the Center for Social Innovation, and Abraham Verghese, MD, professor of medicine and well-known author.

I recently spoke with Verghese about the program.

This is the first time the two schools have worked together to offer a program like this. How did you get involved? 

I have admired the way the Graduate School of Business puts on continuing education programs – they have become so adept at it – so when Dean Lloyd Minor, MD, asked if I would lead this effort from our end, I was excited.

Stanford is all about learning new things and crossing disciplinary boundaries. This is the first medical school at which I’ve worked where all seven schools (business, education, law, engineering, medicine, humanities and sciences, and earth, energy and environmental sciences) are on the same campus. I thought this was a great opportunity for me to learn.

Why is this program needed?

The nature of medicine has become so much more than medicine. It’s a hugely important industry that consumes so much of our gross domestic product. There are so many things the executive has to know that is related to management, marketing, negotiations and strategy, it’s almost inevitable that these two worlds should meet.

But, it’s no use having all these strategies if you don’t ultimately deliver care in a way that’s satisfying to the patient and the people who deliver your care. Medicine is increasingly adopting the robes of business, but it can’t get too far away from what is elemental and fundamental, which is patient care. Every time it does, a disaster follows.

You’re best known for your advocacy of personal, bedside medicine. Why not have a professor who specializes in health-care economics or management lead the program?

I think it’s quite an appropriate role for some who has championed the patient-physician relationship and has been concerned about physician wellness. I’m involved because the patient is at the center, the ultimate beneficiary.

One of the startling things about health care these days is the strange dichotomy between our amazing technologies, therapies and discoveries and yet patients who are as a whole more dissatisfied than ever with the face of medicine, the cost of medicine and the lack of coordination of care. It’s also a time when many physicians are trying to figure out why the joy in medicine has left. For all those reasons, it’s a great time for physician leaders to embrace everything from design thinking to their own wellness.

Looking at it from my lens as a physician-leader of sorts in the educational field, I wish that I’d had the opportunity to attend something like this, using design thinking to examine how to lead in an environment that’s constantly changing, to hear from experts at the business school who talk about negotiating or about personal leadership and vision.

Verghese said he’d go in a “heartbeat” to attend some of the program’s scheduled speakers, including Dean Minor; epidemiologist John Ioannidis, MD, DSc; Doug Owens, MD, director of health policy; and Christy Sandborg, MD, professor of pediatrics.

Previously: Abraham Verghese: “There is no panacea for an investment of time at the bedside with students”, Physician-author Abraham Verghese encourages journalists to tell the powerful stories of medicine and A “grand romp through medicine and metaphor” with Abraham Verghese
Image by Vector Open Stock

If you’ve ever plunged your hand into a tub of ice water, you know about the overlap between cold and pain: that deep, biting ache makes you want to get your hand out of the water – fast. But while the protective value of that sensation is obvious, scientists have always been a bit mystified by how pain-sensing nerves register cold temperatures.

But now, research on a family with an extremely unusual gene mutation may help clarify what’s going on. The mutation, whose discovery was reported online this week in Nature, confers a heightened pain response to cold. The research was initiated by Stanford geneticists and expanded by scientists at three universities in Germany who specialize in hereditary pain syndromes.

The story began with a family who brought their young daughter to Lucile Packard Children’s Hospital Stanford to get help for her unusual episodes of pain. When cold, she experiences pain in her joints that radiates out to her arms and legs. The pain lasts 20 to 30 minutes at a time. The little girl’s father, paternal grandmother, paternal aunt and first cousin (the aunt’s daughter) also experience similar pain episodes, as the new paper explains in detail.

“When we saw her, we were really struck by the fact that the pain was going on in multiple generations of the family,” said one of the study’s authors, medical geneticist Jon Bernstein, MD, PhD. The pattern of inheritance made Bernstein suspect an autosomal dominant disease, in which only one bad copy of a gene causes symptoms. Although several hereditary pain syndromes are described in the medical literature, none matched the exact pattern of symptoms this family experienced, so the Stanford clinicians asked the German scientists to figure out what was going on.

The German team looked for rare mutations shared by the little girl and her cousin, finding one in a gene that codes for an electrical channel in nerve cell membranes. (Nerves transmit electrical signals via flow of charged ions through tiny protein tubes embedded in the cell membrane. There are several types of these channels.) The scientists’ experiments demonstrated that they had discovered a gain-of-function mutation – in which the encoded protein, instead of being rendered nonfunctional, instead alters what it does. In this case, there is a substitution of one amino acid for another in the structure of the affected electrical channel. That change causes pain-sensing nerves to fire at cool temperatures most people don’t find painful.

The same electrical channel, Nav1.9, was also identified as “a key determinant of cold pain sensation” in a paper published earlier this year that examined its activity in rats and mice. That study found that the channel was important to setting animals’ threshold for when cold begins to feel painful, and the new findings fit into that picture nicely.

The German team plans to continue studying the channel’s dynamics to help learn more about the normal threshold between cold and pain, Bernstein said. As for him? “I’m very much looking forward to working with the next family whose case is unsolved,” he told me.

Previously: One mutation, two people and two (or more) outcomes: What gives?, Crying without tears unlocks the mystery of a new genetic disease and Exploring the mystery of pain
Photo by Chris Geatch

Stanford Medicine Unplugged (formerly SMS Unplugged) is a forum for students to chronicle their experiences in medical school. The student-penned entries appear on Scope once a week during the academic year; the entire blog series can be found in the Stanford Medicine Unplugged category. 

Above all, we medical students are told to do no harm. It’s a maxim that we follow religiously and is one of the pillars guiding the ethics of practicing medicine. But our professors don’t tell us what really constitutes harm because it’s not so easy to define.

The first time we touched a patient during a physical exam, we were timid with our hands and instruments, hyperaware of any twitches or jerks that could indicate pain. We made sure to attend to all the patient’s discomforts. Before we entered the room, we adjusted the collars of white coats to appear pleasing. We warmed our hands and dabbed the sweat off our palms. When we palpated his abdomen, we pressed ever so gently, barely making a crater in his stomach. Even when placing our stethoscopes on his chest, we would do so delicately because if we pressed too hard, it would leave a bruise — or so we feared. Reflexes often could not be evoked because we didn’t want to fracture his kneecap by tapping it too hard with our hammers.

When we practice medicine, we walk a tight rope between life and death that has no safety net.

It is easy to conflate the two, but pain is not synonymous with harm. And we must realize that important distinction to practice good medicine. After all, in order to prevent, treat, or even cure disease, we will invariably have to cause the patient some degree of pain, and the physical exam is no exception. We must press the abdomen with enough force to feel the edges of internal organs or shine a blinding light into the pupils. But these tasks cause only relative discomfort.

What about more invasive procedures?

Mammograms can be painful and emotionally draining. Colonoscopies are uncomfortable and awkward. Prostate exams and pap smears force the patient into an undignified and vulnerable position. Even the quickest blood draw can tap into incapacitating needle phobias. And chemotherapy, the epitome of doing good by causing suffering, intends to trade months of agony for potentially years of survival.

So do we give a free pass to those patients who don’t want to undergo these procedures and whom we don’t want to see suffer? The greatest fear of any practitioner is to accidentally hurt the patient, and naturally, we are tempted to the easy route of inaction to avoid this possibility. Ironically, this deep-seated fear that can make us competent and caring physicians can also inhibit us from doing our duty.

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