Friday, April 30, 2021

‘Smart toilet’ monitors for signs of disease

There’s a new disease-detecting technology in the lab of Sanjiv “Sam” Gambhir, MD PhD, and its No. 1 source of data is number one. And number two.

It’s a smart toilet. But not the kind that lifts its own lid in preparation for use; this toilet is fitted with technology that can detect a range of disease markers in stool and urine, including those of some cancers, such as colorectal or urologic cancers. The device could be particularly appealing to individuals who are genetically predisposed to certain conditions, such as irritable bowel syndrome, prostate cancer or kidney failure, and want to keep on top of their health.

“Our concept dates back well over 15 years,” said Gambhir, professor and chair of radiology. “When I’d bring it up, people would sort of laugh because it seemed like an interesting idea, but also a bit odd.” With a pilot study of 21 participants now completed, Gambhir and his team have made their vision of a precision health-focused smart toilet a reality.

Gambhir’s toilet is an ordinary toilet outfitted with gadgets inside the bowl. These tools, a suite of different technologies, use motion sensing to deploy a mixture of tests that assess the health of any deposits. Urine samples undergo physical and molecular analysis; stool assessment is based on physical characteristics.

The toilet automatically sends data extracted from any sample to a secure, cloud-based system for safekeeping. In the future, Gambhir said, the system could be integrated into any health care provider’s record-keeping system for quick and easy access.

A paper describing the research was published April 6 in Nature Biomedical Engineering. Gambhir is the senior author. Seung-min Park, PhD, senior research scientist; David Won, MD, PhD, former visiting scholar in the Molecular Imaging Program at Stanford; and postdoctoral scholar Brian Lee, PhD, share lead authorship.

Pulling double duty

The toilet falls into a category of technology known as continuous health monitoring, which encompasses wearables like smart watches. “The thing about a smart toilet, though, is that unlike wearables, you can’t take it off,” Gambhir said. “Everyone uses the bathroom — there’s really no avoiding it — and that enhances its value as a disease-detecting device.”

Although the idea may take some getting used to, Gambhir, who holds the Virginia and D.K. Ludwig Professorship for Clinical Investigation in Cancer Research, envisions the smart toilet as part of the average home bathroom. In facilitating that broad adaption, Gambhir designed the “smart” aspect as an add-on — a piece of technology that’s readily integrated into any old porcelain bowl. “It’s sort of like buying a bidet add-on that can be mounted right into your existing toilet,” he said. “And like a bidet, it has little extensions that carry out different purposes.”

These extensions sport an array of health-monitoring technologies that look for signs of disease. Both urine and stool samples are captured on video and are then processed by a set of algorithms that can distinguish normal “urodynamics” (flow rate, stream time and total volume, among other parameters) and stool consistencies from those that are unhealthy.

Alongside physical stream analysis, the toilet also deploys uranalysis strips, or “dipstick tests,” to measure certain molecular features. White blood cell count, consistent blood contamination, certain levels of proteins and more can point to a spectrum of diseases, from infection to bladder cancer to kidney failure. In its current stage of development, Gambhir said, the toilet can measure 10 different biomarkers.

It’s still early days, though, with a total of 21 participants having tested the toilet over the course of several months. To get a better feel for “user acceptance” more broadly, the team surveyed 300 prospective smart-toilet users. About 37% said they were “somewhat comfortable” with the idea, and 15% said they were “very comfortable” with the idea of baring it all in the name of precision health.

ID please

One of the most important aspects of the smart toilet may well be one of the most surprising — and perhaps unnerving: It has a built-in identification system. “The whole point is to provide precise, individualized health feedback, so we needed to make sure the toilet could discern between users,” Gambhir said. “To do so, we made a flush lever that reads fingerprints.” The team realized, however, that fingerprints aren’t quite foolproof. What if one person uses the toilet, but someone else flushes it? Or what if the toilet is of the auto-flush variety?

They added a small scanner that images a rather camera-shy part of the body. You might call it the polar opposite of facial recognition. In other words, to fully reap the benefits of the smart toilet, users must make their peace with a camera that scans their anus.

“We know it seems weird, but as it turns out, your anal print is unique,” Gambhir said. The scans — both finger and nonfinger — are used purely as a recognition system to match users to their specific data. No one, not you or your doctor, will see the scans.

By no means is this toilet a replacement for a doctor, or even a diagnosis, Gambhir said. In fact, in many cases, the toilet won’t ever report data to the individual user. In an ideal scenario, should something questionable arise — like blood in the urine — an app fitted with privacy protection would send an alert to the user’s health care team, allowing professionals to determine the next steps for a proper diagnosis. The data would be stored in a secure, cloud-based system. Data protection, both in terms of identification and sample analyses, is a crucial piece of this research, Gambhir said. “We have taken rigorous steps to ensure that all the information is de-identified when it’s sent to the cloud and that the information — when sent to health care providers — is protected under HIPAA,” he said, referring to the Health Insurance Portability and Accountability Act, which restricts the disclosure of health care records.

Smart toilet 2.0

As Gambhir and his team continue to develop the smart toilet, they’re focusing on a few things: increasing the number of participants, integrating molecular features into stool analysis and refining the technologies that are already working. They’re even individualizing the tests deployed by the toilet. For example, someone with diabetes may need his or her urine monitored for glucose, whereas someone else who is predisposed to bladder or kidney cancer might want the toilet to monitor for blood.

Gambhir’s other goal is to further develop molecular analysis for stool samples. “That’s a bit trickier, but we’re working toward it,” Gambhir said. “The smart toilet is the perfect way to harness a source of data that’s typically ignored — and the user doesn’t have to do anything differently.”

Thursday, April 22, 2021

Polynesians, Native Americans made contact before European arrival, genetic study finds

Through deep genetic analyses, Stanford Medicine scientists and their collaborators have found conclusive scientific evidence of contact between ancient Polynesians and Native Americans from the region that is now Colombia — something that’s been hotly contested in the historic and archaeological world for decades.

“Genomics is at a stage where it can really make useful contributions to answering some of these open questions,” said Alexander Ioannidis, PhD, a postdoctoral scholar at Stanford. “I think it’s really exciting that we, as data scientists and geneticists, are able to contribute in a meaningful way to our understanding of human history.”

Before this study was conducted, proponents of Native American and Polynesian interaction reasoned that some common cultural elements, such as a similar word used for a shared agricultural staple, hinted that the two populations had mingled before Europeans settled in South America. Those who disagreed pointed to studies with contrasting conclusions and the fact that the two groups were separated by thousands of miles of open ocean.

This new study is the first to show, through conclusive genetic analyses, that the two groups indeed encountered one another, and did so before Europeans arrived in South America. To conduct the study, Ioannidis and a team of international researchers collected genetic data from more than 800 living Indigenous inhabitants of several South American countries, Mexico and Polynesia, conducting extensive genetic analyses to find signals of common ancestry. Based on trackable, heritable segments of DNA, the team was able to trace common genetic signatures of Native American and Polynesian DNA back hundreds of years.

“Our laboratory in Mexico has been very interested in understanding the genetic diversity of populations throughout Latin America and, more generally, of underrepresented populations in genomic research,” said AndrĂ©s Moreno-Estrada, PhD, professor and head of genomic services at the National Laboratory of Genomics for Biodiversity in Mexico. “Through this research, we wanted to reconstruct the ancestral roots that have shaped the diversity of these populations and answer deep, long-standing questions about the potential contact between Native Americans and Pacific Islanders, connecting two of the most understudied regions of the world.”

A paper detailing the study was published July 8 in Nature. Ioannidis, who conducted much of this work while a graduate student at Stanford’s Institute for Computational and Mathematical Engineering,  shares lead authorship with Stanford graduate student Javier Blanco-Portillo. Moreno-Estrada is the senior author.

The mystery of the sweet potato

Before the study brought scientific evidence to the debate, the idea that Native Americans and Polynesians had crossed paths originated from a complex — both in its structure and origins — carbohydrate: the sweet potato. It turns out the sweet potato, which was originally domesticated in South and Central America, has also been known to grow in one other place prior to European contact. That place is known as Oceania, which consists of many islands, including the Polynesian islands.

“The sweet potato is native to the Americas, yet it’s also found on islands thousands of miles away,” Ioannidis said. “On top of that, the word for sweet potato in Polynesian languages appears to be related to the word used in Indigenous American languages in the Andes.”

The overlap in culture made some archaeologists and historians think it was not only feasible, but likely, that the potato’s arrival in Polynesia was the result of the two peoples mingling.

The researchers believe that the Polynesians landed in what is now Colombia. It is also possible, though less likely due to their coastal travel norms, that one or two ships carrying Native Americans could have sailed off course and run into Polynesia, Ioannidis said.

Without scientific evidence, the idea of overlap was just conjecture. Earlier, other groups of researchers turned to the genetics of the sweet potato, hoping to show that the domesticated potatoes from South America and Polynesia were genetically one and the same. But their efforts to trace the tubers have been inconclusive, as the sweet potato’s genetic origins were too complex to definitively point to human-mediated spread.

Other studies have analyzed ancient DNA from bones belonging to Native Americans and native Polynesians. Ancient DNA samples, however, are often degraded, so these studies were unable to provide sufficient evidence that the two populations shared a moment in history.

Carriers of history

Ioannidis’ team took a different, big data approach, analyzing the DNA of hundreds Indigenous people from Polynesia, Mexico and South America. Before collecting any samples or conducting genetic analyses, the researchers visited the communities to explain the study, gauge interest in participation and ask for consent. The scientists then collected saliva samples from 807 participants on 17 Polynesian islands and 15 Native American groups along the Pacific coast of the Americas from Mexico to Chile, conducting genetic analyses to look for snippets of DNA that are characteristic of each population and for segments that are “identical by descent,” meaning they are inherited from the same ancestor many generations ago.

“We found identical-by-descent segments of Native American ancestry across several Polynesian islands,” Ioannidis said. “It was conclusive evidence that there was a single shared contact event.” In other words, Polynesians and Native Americans met at one point in history, and during that time people from the two cultures produced children with both Native American and Polynesian DNA. Statistical analyses confirmed the event occurred in the Middle Ages, around A.D. 1200, which is “around the time that these islands were originally being settled by native Polynesians,” Ioannidis said. Using computational methods developed as part of Ioannidis’ graduate work, the team then localized the source of the Native American DNA to modern-day Colombia.

“If you think about how history is told for this time period, it’s almost always a story of European conquest, and you never really hear about everybody else,” Ioannidis said. “I think this work helps piece together those untold stories — and the fact that it can be brought to light through genetics is very exciting to me.”

Human biology registers two seasons, not four, study suggests

As kids, we learn there are four seasons, but researchers at the Stanford School of Medicine have found evidence to suggest that the human body doesn’t see it this way.

“We’re taught that the four seasons — winter, spring, summer and fall — are broken into roughly equal parts throughout the year, and I thought, ‘Well, who says?’” Michael Snyder, PhD, professor and chair of genetics, said. “It didn’t seem likely that human biology adheres to those rules. So we conducted a study guided by people’s molecular compositions to let the biology tell us how many seasons there are.”

Four years of molecular data from more than 100 participants indicate that the human body does experience predictable patterns of change, but they don’t track with any of Mother Nature’s traditional signals. Overall, Snyder and his team saw more than 1,000 molecules ebb and flow on an annual basis, with two pivotal time periods: late spring-early summer and late fall-early winter. These are key transition periods when change is afoot — both in the air and in the body, said Snyder, who is the Stanford W. Ascherman, MD, FACS, Professor in Genetics.

“You might say, ‘Well, sure, there are really only two seasons in California anyway: cold and hot,” Snyder said. “That’s true, but even so, our data doesn’t exactly map to the weather transitions either. It’s more complicated than that.”

Snyder hopes that observations from this study — of higher levels of inflammatory markers in the late spring, or of increased markers of hypertension in early winter, for example — can provide a better foundation for precision health and even help guide the design of future clinical drug trials.

One caveat, Snyder said, is that the team conducted the research with participants in Northern and Southern California, and it’s likely that the molecular patterns of individuals in other parts of the country would differ, depending on atmospheric and environmental variations.

The study was published online Oct. 1 in Nature Communications. Snyder is the senior author. Postdoctoral scholars Reza Sailani, PhD, and Ahmed Metwally, PhD, share lead authorship.

Spring-ish and winter-ish

The study was conducted in 105 individuals who ranged in age from 25 to 75. About half were insulin resistant, meaning their bodies don’t process glucose normally. About four times a year, the participants provided blood samples, which the scientists analyzed for molecular information about immunity, inflammation, cardiovascular health, metabolism, the microbiome and much more. The scientists also tracked the exercise and dietary habits of all participants.

Over the span of four years, data showed that the late-spring period coincided with a rise in inflammatory biomarkers known to play a role in allergies, as well as a spike in molecules involved in rheumatoid arthritis and osteoarthritis. They also saw that a form of hemoglobin called HbA1c, a protein that signals risk for Type 2 diabetes, peaked during this time, and that the gene PER1, which is known to be highly involved in regulating the sleep-wake cycle, was also at its highest.

In some cases, Snyder said, it’s relatively obvious why levels of molecules increased. Inflammatory markers probably spike due to high pollen counts, for instance. But in other cases, it’s less obvious. Snyder and his team suspect that HbA1c levels are high in the late spring because of the often indulgent eating that accompanies the holidays —  HbA1c levels reflect dietary habits from about three months before measurements are taken — as well as a general waning of exercise in the winter months. 

As Snyder and his team followed the data into early winter, they saw an increase in immune molecules known to help fight viral infection and spikes of molecules involved in acne development. Signatures of hypertension, or high blood pressure, were also higher in the winter.

The data also showed that there were some unexpected differences in the microbiomes of individuals who were insulin resistant and those of individuals who processed glucose normally. Veillonella, a type of bacteria involved in lactic acid fermentation and the processing of glucose, was shown to be higher in insulin-resistant individuals throughout the year, except during mid-March through late June.

Parsing seasonality

“Many of these findings open up space to investigate so many other things,” Sailani said. “Take allergies, for instance. We can track which pollens are circulating at specific times and pair that with personalized readouts of molecular patterns to see exactly what a person is allergic to.”

The hope is that more information about a person’s molecular ups and downs will allow them to better understand the context of their body’s biological swings and will enable them to use that information to proactively manage their health.

“If, for instance, your HbA1C levels are measured during the spring and they seem abnormally high, you can contextualize that result and know that this molecule tends to run high during spring,” Snyder said. “Or, you could see it as a sort of kick in the pants, so to speak, to exercise more during the winter in an effort to keep some of these measurements down.”

Even more broadly speaking, these findings could also help inform the design of drug trials. For example, if researchers are hoping to test a new drug for hypertension, they would likely benefit from knowing that because hypertension seems to spike in the early winter months, trials that started in winter versus spring would likely have different outcomes.

In darkness, loneliness, Stanford Medicine chaplains bring peace, strength and hope

In the rooms of COVID-19 patients at Stanford's hospitals, among the tubes, monitors and masked care providers, Samuel Nkansah brings spiritual care to the patients' bedside.

Nkansah is a board-certified chaplain (BCC), who as a member of Stanford's Spiritual Care Service team helps support and connect patients with their faith.

Nkansah recalls the first time he entered the room of a COVID-19 patient. The moment he came near, the patient -- a person in palliative care so ill he could not speak -- reached out to him.

By the patient's bedside, the two locked their hands together. "I could see his tears flowing forth, and I too shared tears with him," Nkansah said. "It dawned on me that day -- COVID-19 patients are robbed of a fundamental need: human touch."

In the many months since, he has clasped hands with many COVID-19 patients, providing connection, support.

"If you are being carried away down a fast-flowing river, you will reach out and grab anything for help," Nkansah said. "Even if what passes you are cobwebs, you reach out."

Although he is the only chaplain meeting with COVID-19 patients in person right now, the rest of the spiritual care team has not let physical distance deter them from providing care.

Faith at the bedside

Last December, a severely ill COVID-19 patient of Jewish faith was in the hospital during Hanukkah.

"This patient was very close with his brother, who, under any other circumstance, would have come to the hospital," said Bruce Feldstein, MD, BCC. The care team had been in touch with the brother and knew he and the patient were worried and feeling isolated. "Being in the hospital with COVID-19 is anguish enough, but all while alone and during a special holiday, those feelings are amplified."

To help, Feldstein turned to two of the patient's nurses, sharing with them the idea of Hanukkah as a representation of holding onto hope, and giving them a photo of a menorah to symbolize the support and unity they all shared with the patient during that time.

"As a nurse I feel it's important that the patient not only receives medical care, but that they're cared for spiritually, too, because it can be an important part to their recovery," said Rocio Nunez, RN. She and another nurse placed the photo at the patient's bedside and wished him a happy Hanukkah. "We took a picture, sent it to his sibling and relayed the story, which was comforting for everyone involved," said Feldstein. "It feels immensely meaningful that, in the middle of all this darkness, there are still these points of light, where human touch and kindness shine through."

Connecting with your source of strength, comfort

Health care chaplains come from a variety of spiritual backgrounds but they support people of any and all faiths. Nkansah is a Catholic priest. Feldstein is of Jewish faith, and their colleague Anna Nikitina, BCC, who works with palliative and intensive care patients, is an Orthodox Christian.

"When I am with a patient, if they are Buddhist, I invite them to call upon Buddha; if they are Muslim, I invite them to call upon the Almighty Allah; if they are Christian, I invite them to call upon God. And then I invite them to let that source of strength lead them," said Nkansah. "I find that this helps them feel less anguish, more comfort, and more ready to comply with what the medical care team asks of them."

Humans find spiritual meaning in myriad ways, Feldstein told me. When he visits a patient (in-person after they've recovered and virtually) his intention is to meet them in their world as they see it. "If I had to pick out a single verb to describe what we do, it would be 'accompany.' That's the core of the service we provide, we accompany you in your spiritual world, and help connect you with your source of strength, comfort or meaning, whatever that is for you."

The crab and the wave

The chaplains tread in treacherous waters -- where infection is near and fear and loneliness are heightened.

"Often, my colleagues will ask me, 'Father Samuel, how are you so calm about this? Why aren't you afraid?' And I tell them, I learn from the crab.

Nkansah, who grew up in Ghana, says there's a saying that comes from the coastal towns of Ghana: The crab cannot be bothered by the storms and crashing waves of the sea.

Nkansah explains: If a crab is not careful, it could get dragged out to sea. But it has learned. If it sees a wave coming, the crab digs its legs firmly in the sand so that when the wave hits, it may feel the wave's force, but it will not be carried away.

"I see COVID-19 as the sea storm and, as a chaplain, I see myself as the crab, walking to my patients amid all the stormy weather. If I become scared or emotional, how will I be able to take my gorgeous walk on the seashore, knowing that what I do with and for people in the hospital is needed?" said Nkansah. "When I see a wave coming, I do not need haste, neither do I need to panic. I do my own spiritual practices, I collect myself, I stay nourished and hydrated, and that is how I stay grounded."

Reflecting together

Feldstein and the other chaplains also provide spiritual care for providers -- the comforter of the comforters, Nkansah says. Early on in the pandemic, Feldstein created Reflection Rounds, where health care workers and medical students can gather in person on a regular basis to support one another.

"It's a session that's facilitated by a chaplain and a physician during which a small group of colleagues, be it doctors, nurses, residents or other hospital staff, can come together and discuss their experiences on emotional, spiritual level," said Feldstein. "We talk about the things that don't get talked about at regular rounds, or the kinds of experiences you can't share with people outside of the hospital because they just won't understand."

The reflections, launched in response to the pandemic, have helped care providers from around the hospital connect and support one another through plausibly the most difficult time of their career, said Feldstein. "We're all people who have said yes to medicine and to healing. And because of that commitment, there's a shared understanding that bonds, nourishes and strengthens us."

Inspiration in a trying time

The chaplains have found that COVID-19 patients are often suffering from another severe ailment: loneliness. Their role in kindling hope and strength through family and faith has become even more pressing, said Nikitina.

"A big part of this role is to help facilitate the connection between patients and their families," Nikitina said. "I call the families of patients to tell them I've just been with their loved one, and I assure them that, alongside their medical care team, there is someone at the hospital tending to their spiritual well-being, too."

She provides direct support for the families as well, often leading or participating in prayers over the phone for recovery. Her prayers are tailored for each patient or family member. A patient recovering from a lung transplant as a result of severe COVID-19, for example, asked that Nikitina send a prayer of gratitude to God, to say thank you for answering his prayers, and for seeing him through this life-saving surgery.

"I am newly inspired by the patients that I see every day," said Nikitina. "Seeing the resilience and how they find strength to cope with the illness, and the desire to strive for wellness and healing -- their bravery. Just being a witness to this gives me strength to continue my work."