Imagine, Surgery Without a Scar

A new study shows that a 20-year-old drug prevents scarring in mice. If it works on humans, it could change the lives of those with disfiguring wounds.Cleft palates that close without scars. Burn wounds that recover without a trace of injury. Years-old disfiguring scars that disappear, leaving skin smooth and flawless.It sounds like science fiction, but healing without scarring may become a tantalizing possibility. In a study published Thursday in Science, two researchers at Stanford University report that they have figured out the molecular signals that make scars form and found a simple way to block them — at least in mice.A 20-year-old drug, verteporfin, already on the market as an intravenous treatment for macular degeneration, can prevent scarring if it is injected at the edge of a wound.As the verteporfin-treated wounds heal, the skin that forms looks perfectly normal, nothing like skin that heals with scars, those lumpy wound closures that are not only unsightly but also much weaker than normal skin and have no hair, or oil and sweat glands.The study involved mice, but the researchers, Dr. Michael Longaker, Stanford’s vice chair of surgery, and Geoffrey Gurtner, Stanford’s vice president of surgery for innovation, have now moved on to pigs, whose skin is closest to that of humans. With these new subjects, the surgeons made an incision as wide as a thumb and five inches long. When they sutured the cut and injected verteporfin around the edge, there was dramatically less scarring.“It’s pretty spectacular,” Dr. Longaker said.Researchers who study wounds and who were not associated with the study were enthusiastic.“It is unusual for me to read a paper and say, ‘Wow, this is really a major advance,’” said Valerie Horsley, a tissue developmental biologist at Yale who studies wound healing. “But this is a major advance.”Marjana Tomic-Canic, director of the wound healing and regenerative medicine program at the University of Miami Miller School of Medicine, said that the study is “really a leap,” adding, “everyone will get excited about this work.”Dr. Longaker said that he hoped to get permission from the Food and Drug Administration by the end of the year to test the safety and efficacy of the drug in babies with cleft lips and palates.For Dr. Longaker, speed is of the essence if the treatment works and is safe. “I don’t want this to be a 10-year journey,” he said.Stanford has filed patents for the use of verteporfin in scar formation.Although verteporfin is available, and doctors can prescribe drugs for unapproved uses, Dr. Longaker says that it’s crucial to wait for F.D.A. approval before using the drug to try to prevent scars.“Obviously we want to help patients as soon as possible,” he said. “But we’ve got to make sure this drug is tested in a way that ensures safety and efficacy.”The history of medicine, he said, offers a sobering picture of treatments that looked good in animals but failed in clinical trials.If the drug works on humans, the discovery stands to be lucrative and life transforming. Hundreds of millions of people are seriously scarred each year, and many of those scars are disfiguring — from accidents, as well as from heart bypass surgeries, mastectomies and burns.“Scars in general cause pain and itching and prevent us from moving the way we should,” said Dr. Benjamin Levi, a burn specialist who directs the Center for Organogenesis and Trauma at the University of Texas Southwestern Medical Center. The possibility of blocking the scarring process “has huge potential,” he said.Dr. Jason A. Spector, professor of plastic surgery and otolaryngology at Weill Cornell Medical College, said that when he does reconstructive surgery on patients with head and neck cancer, many “are more concerned about the scar through their lip and skin than about the cancer itself.”Dr. Longaker’s obsession with scars began with an experiment in 1987 as a new postdoctoral fellow in the lab of Dr. Michael R. Harrison at the University of California, San Francisco. Dr. Harrison, who was studying fetal surgery, suggested that Dr. Longaker operate on a fetal lamb two-thirds of the way through pregnancy and then return the fetus to its mother’s womb to continue developing.Dr. Longaker gasped when he later delivered the baby lamb. Its skin was intact. There were no scars to be seen.“I will never forget that moment,” he said.He went on to become a pediatric plastic surgeon and saw firsthand the scarring on children after they had undergone operations for cleft lips or palates. And he ran a lab devoted to figuring out how to prevent scars.He learned that for the first two trimesters of fetal life, skin is gelatinous, “like a bowl of Jell-O,” Dr. Longaker said. Then, as the fetus develops to live outside the sterile liquid world of the womb, the skin forms a barrier to prevent water loss and block the entry of microorganisms. At that point, breach of the skin barrier could be deadly, so the body switches on a system that lets it quickly seal it.But there is a trade-off for speed in healing a wound, Dr. Longaker noted. “The cost is loss of form and function.” And scar formation.Dr. Tomic-Canic described the process: When there is a wound, the strong muscle under the skin contracts and brings the edges of the wound together. A clot forms as a temporary barrier over the wound, and under it, the body makes thick coils of collagen rope that form a bridge so skin cells can migrate across the gap and fill in the opening. Those collagen ropes remain — they are the scar.As molecular biology and molecular genetics advanced, Dr. Longaker seized on the new tools to probe the molecular pathways needed to form scars. The key starting point for scarring is mechanical tension when a wound tears skin that should be taut. (Older people with loose skin are less likely to scar because their skin is under less tension.) The tear in the layers of skin prompts a type of skin cell — fibroblasts — to create collagen ropes and initiates a chain reaction of molecular events inside the skin cells. The reactions culminate in the activation of a protein called YAP, for Yes-associated protein. YAP then binds to DNA, and scarring begins.Dr. Longaker and Dr. Gurtner bred mice without the YAP protein. Because mice have loose skin, the two had to hold the wounds open with a ring, like an embroidery hoop, to mimic the tension in human skin. The wounds healed. No scars.They then asked: Could verteporfin have the same effect as the absence of YAP? So in another experiment, they wounded mice that could make YAP and once again held the loose skin taut with rings. They injected verteporfin around the wound. They waited to see what would happen.Dr. Longaker remembers the moment. “Holy guacamole,” he said. The healed wounds looked just like normal skin. They were the same under the microscope. They grew hair. They had oil glands.His imagination soared. He might be able to prevent scars with a few quick injections of verteporfin. And there was no reason to think he couldn’t go even farther. A patient who had a disabling and disfiguring scar could go to a surgeon who could dab the scar with lidocaine to numb the skin, cut open the scar, inject verteporfin around the edges, and close the wound. Would it reheal without the scar?“That could change their lives,” Dr. Longaker said.Dr. Spector said he doubted all doctors would wait until F.D.A. approval if early clinical data supported the laboratory studies. Some are sure to jump ahead and try it because there is nothing now to stop scarring.Dr. Longaker hopes doctors hold off. Clinical trials must come first, he stressed, and safety must be assured.“I get it,” he said. “No one is more excited than me.”“To be honest,” he added, “I’ve been waiting for 34 years. I would love to use it. This is a big deal. But that doesn’t mean we shortcut the process.”

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The Nervous Person’s Guide to Re-Entering Society

How to cope with a less cautious world as pandemic restrictions loosen.Amy Beigel, a fifth-grade teacher in Charlotte, N.C., has already had Covid-19. Her husband did, too. And now both of them have received their first dose of the vaccine. But when she thinks about gathering with other people outdoors this summer, she hesitates.The desire to see friends and extended family is definitely there, said Ms. Beigel, 40, a mother of four. “But then we shoot the idea down.”There are the weighty questions: “What if people came and did get sick?” she asked. The social awkwardness: “You don’t want to put undue pressure on someone.” And the logistical details: “Do you serve food?”“I don’t know,” she said. “Maybe it’s too complicated.”For the last year, public health experts have told us time and again that if you don’t socially distance and wear a mask, you could die. So, as more people get vaccinated and we accelerate toward a new normal, is it any wonder that some people are feeling hesitant to let go of those precautions?The official recommendations have already started to change. The Centers for Disease Control and Prevention now says that fully vaccinated people can travel safely in the United States; and that people in a fully vaccinated household can visit an unvaccinated household indoors without masks or social distancing, provided that they are at low risk for severe Covid-19. As we approach summer, the agency may further loosen guidelines if coronavirus cases plummet.We asked experts how best to ease back into society as our worlds broaden beyond life at home.If you don’t want to jump into the pool, dip your toe in first.For those who have remained cautious throughout the pandemic, it’s normal to feel unmoored by fewer safety precautions.“It would be disingenuous for us to say, ‘Eh, you’re fine. Go for it, it’s all good now,’” said Dr. Joshua Barocas, an infectious diseases physician at Boston Medical Center.Instead, find incremental ways of phasing back into interactions with people, he recommended.Dr. Barocas likened it to jumping into a cold swimming pool. If you can’t bring yourself to do a cannonball, first you dip one toe in and enter gradually.Sharrona Pearl, 43, who lives in Philadelphia and is fully vaccinated, said she recently decided that it felt OK to have a cup of tea indoors with a vaccinated friend.“I have three kids who are not vaccinated,” she said. “It’s really hard because they can’t have friends over for play dates, right? They just can’t. It’s not OK. So here I am doing it — that’s sort of frustrating for them.”Hosting a friend indoors is just one of “dozens of points of re-entry,” said Ellen Hendriksen, a clinical psychologist in Boston and the author of “How to Be Yourself: Quiet Your Inner Critic and Rise Above Social Anxiety.”You might start out by taking public transportation once a week, for example, or visiting the grocery store more often. Eventually, you might gradually work your way up to something like a wedding or a graduation.This is assuming, of course, that you want to do these things.If you don’t yet, that’s OK. But it’s best to address your worries if they are preventing you from living the way that you want to live, or keeping you from activities that give your life meaning and purpose.Anxiety is maintained by avoidance and driven by uncertainty, Dr. Hendriksen said.Don’t wait for the anxiety to go away.As long as things you want to do are considered safe or very low risk, don’t wait until the day when you have zero anxiety about doing them.“Feeling anxious doesn’t mean you’re in danger, doesn’t mean something is wrong,” Dr. Hendriksen said. In fact, she added, it is a normal part of entering post-pandemic life.It can be helpful to engage in calming, validating self-talk, suggested Lina Perl, a clinical psychologist in New York City. Speak to yourself in a safe, reassuring voice, much like an encouraging parent might do with their child on the first day of school.Ask yourself, “What kind of world do I want to live in? Have I done all the things I have to do to make me safe?” Dr. Perl said. Then think about the tough things you’ve done before and how you pushed through them.“In order to live in the world, you need to be able to tolerate a certain amount of uncertainty and a certain amount of risk,” she said. When you start doing something new, “It can be uncomfortable, but the more you do it, the less power it has over you.”“Think of your nervous system like a pet,” she added. Train your nervous system to recognize that you are not in danger by doing the very activities that might make you a little anxious. Once you’re in that situation, try to stay there until the anxiety starts to fade, she said.But if your anxiety is bringing disproportionate distress or your life is impaired in some way, the experts said you may want to speak with a therapist or other trusted support person like a religious leader, who can guide and nudge you in a positive direction.You do not have to replicate what you did in the ‘before times.’One positive aspect of the pandemic is that it has made us question the things in our lives that were draining, such as overbooking our social calendar or commuting to work five days a week, and embrace positive things like spending more time with family. It also led to new habits that help us avoid disease, such as mask-wearing, which wasn’t typically done in the United States.Even after coronavirus cases and death rates plummet, you can choose to hold on to some of the current public health recommendations if it helps ease your fears. Frequent hand-washing? Great, that’s beneficial against a host of pathogens. Wearing face masks during the winter? It’s not only reasonable but prudent if you take public transportation regularly or live in a place with high population density. Some people might also choose to continue to wear masks in any situation where they are surrounded by large groups of people. Others might forgo handshakes in favor of elbow taps or a hand-over-heart gesture.Don’t compare yourself to what other people are doing or look to others for the right answer. “That, I think, actually creates more of an anxious churn,” Dr. Perl said.Let go of resentment.As the adage goes, you cannot control other people, only yourself. Anger, frustration and resentment toward people who either ignore public health guidelines or behave differently than you do will only raise your stress level.Instead of thinking, “Those people should be wearing a mask right now,” try thinking, “I wish those people were wearing a mask.” The two statements are similar, but the latter can help temper our emotional reaction, Dr. Hendriksen said.The C.D.C. continues to recommend masks and distancing in most situations. But when you’re outside and at least six feet from other people, the risks of contracting Covid-19 are very low even if nobody is wearing a mask, experts say. That’s especially true if you are vaccinated.Prioritize activities that help reduce anxiety.If you developed a love affair with processed foods and neglected fruits and vegetables during lockdown, start incorporating healthy foods back into your diet. And if you stopped exercising during the pandemic, start moving again. By taking care of your body you are also taking care of your mind.Dr. John Ratey, an associate clinical professor of psychiatry at Harvard Medical School who studies the effects of exercise on the brain, said aerobic exercise like a simple bike ride or brisk walk can help people with chronic anxiety or even those who are nervous about an upcoming test or an important meeting.Exercise elevates brain activity, he said: “With that, you elevate the concentration of all these good neurotransmitters and neurohormones that we have that help us feel better, feel calmer, feel less anxious.”See how you feel after putting in a half-hour of yoga or 15 minutes of aerobic exercise, Dr. Ratey said. Eventually, “you will increase your resilience and your ability to take challenges like going out without a mask or visiting your kids or your grandkids when everybody has the vaccine,” he said. “But it’s going to be a transition period, for sure.”

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Artificial intelligence model predicts which key of the immune system opens the locks of coronavirus

With an artificial intelligence (AI) method developed by researchers at Aalto University and University of Helsinki, researchers can now link immune cells to their targets and, for example, uncouple which white blood cells recognize SARS-CoV-2. The developed tool has broad applications in understanding the function of the immune system in infections, autoimmune disorders, and cancer.
The human immune defense is based on the ability of white blood cells to accurately identify disease-causing pathogens and to initiate a defense reaction against them. The immune defense is able to recall the pathogens it has encountered previously, on which, for example, the effectiveness of vaccines is based. Thus, the immune defense the most accurate patient record system that carries a history of all pathogens an individual has faced. This information however has previously been difficult to obtain from patient samples.
The learning immune system can be roughly divided into two parts, of which B cells are responsible for producing antibodies against pathogens, while T cells are responsible for destroying their targets. The measurement of antibodies by traditional laboratory methods is relatively simple, which is why antibodies already have several uses in healthcare.
“Although it is known that the role of T cells in the defense response against for example viruses and cancer is essential, identifying the targets of T cells has been difficult despite extensive research,” says Satu Mustjoki, Professor of Translational Hematology.
AI helps to identify new key-lock pairs
T cells identify their targets in a key and a lock principle, where the key is the T cell receptor on the surface of the T cell and the key is the protein presented on the surface of an infected cell. An individual is estimated to carry more different T cell keys than there are stars in the Milky Way, making the mapping of T cell targets with laboratory techniques cumbersome.

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Freeze! Executioner protein caught in the act

A new molecular ‘freeze frame’ technique has allowed WEHI researchers to see key steps in how the protein MLKL kills cells.
Small proteins called ‘monobodies’ were used to freeze MLKL at different stages as it moved from a dormant to an activated state, a key process that enables an inflammatory form of cell death called necroptosis. The team were able to map how the three-dimensional structure of MLKL changed, revealing potential target sites that might be targets for drugs — a potential new approach to blocking necroptosis as a treatment for inflammatory diseases.
The research, which was published in Nature Communications, was led by Associate Professor James Murphy and PhD students Ms Sarah Garnish and Mr Yanxiang Meng, in collaboration with Assistant Professor Akiko Koide and Professor Shohei Koide from New York University, US.
At a glance The ‘executioner’ protein MLKL kills cells through an inflammatory process called necroptosis. Monobody technology has enabled WEHI researchers to capture different forms of MLKL as it becomes activated and moves to kill the cell. Understanding how the three-dimensional shape of MLKL changes may lead to the development of drugs that prevent necroptosis, as a treatment for inflammatory diseases.Key steps in necroptosis
MLKL is a key protein in necroptosis, being the ‘executioner’ that kills cells by making irreparable holes in their exterior cell membrane. This allows the cell contents to leak out and triggers inflammation — alerting nearby cells to a threat, such as an infection.

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Poor iodine levels in women pose risks to fetal intellectual development in pregnancy

An increasing number of young women are at increased risk of having children born with impaired neurological conditions, due to poor iodine intake.
Dietary changes, including a growing trend towards the avoidance of bread and iodised salt, as well as a reduced intake of animal products containing iodine can contribute to low iodine levels.
A small pilot study undertaken by the University of South Australia (UniSA) comparing iodine levels between 31 vegan/plant-based participants and 26 omnivores has flagged the potential health risk.
Urine samples showed iodine readings of 44 ug/L in the plant-based group, compared to the meat eaters’ 64 ug/L level. Neither group came close to the World Health Organization’s recommended 100 grams per litre.
Participants from both groups who chose pink or Himalayan salt instead of iodised salt had severely deficient iodine levels, averaging 23 ug/L.
The findings have been published in the International Journal of Environmental Research and Public Health.

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Faster air exchange in buildings not always beneficial for coronavirus levels

Vigorous and rapid air exchanges might not always be a good thing when it comes to addressing levels of coronavirus particles in a multiroom building, according to a new modeling study.
The study suggests that, in a multiroom building, rapid air exchanges can spread the virus rapidly from the source room into other rooms at high concentrations. Particle levels spike in adjacent rooms within 30 minutes and can remain elevated for up to approximately 90 minutes.
The findings, published online in final form April 15 in the journal Building and Environment, come from a team of researchers at the U.S. Department of Energy’s Pacific Northwest National Laboratory. The team includes building and HVAC experts as well as experts in aerosol particles and viral materials.
“Most studies have looked at particle levels in just one room, and for a one-room building, increased ventilation is always useful to reducing their concentration,” said Leonard Pease, lead author of the study. “But for a building with more than one room, air exchanges can pose a risk in the adjacent rooms by elevating virus concentrations more quickly than would otherwise occur.
“To understand what’s happening, consider how secondhand smoke is distributed throughout a building. Near the source, air exchange reduces the smoke near the person but can distribute the smoke at lower levels into nearby rooms,” Pease added. “The risk is not zero, for any respiratory disease.”
The team modeled the spread of particles similar to SARS-CoV-2, the virus that causes COVID-19, via air-handling systems. Scientists modeled what happens after a person has a five-minute coughing bout in one room of a three-room small office building, running simulations with particles of five microns.

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More belly weight increases danger of heart disease even if BMI does not indicate obesity

People with abdominal obesity and excess fat around the body’s mid-section and organs have an increased risk of heart disease even if their body mass index (BMI) measurement is within a healthy weight range, according to a new Scientific Statement from the American Heart Association published today in the Association’s flagship journal, Circulation.
“This scientific statement provides the most recent research and information on the relationship between obesity and obesity treatment in coronary heart disease, heart failure and arrhythmias,” said Tiffany M. Powell-Wiley, M.D., M.P.H., FAHA, chair of the writing committee and a Stadtman Tenure-Track Investigator and chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory in the Division of Intramural Research at the National Heart, Lung, and Blood Institute at the National Institutes of Health in Bethesda, Maryland. “The timing of this information is important because the obesity epidemic contributes significantly to the global burden of cardiovascular disease and numerous chronic health conditions that also impact heart disease.”
A greater understanding of obesity and its impact on cardiovascular health highlights abdominal obesity, sometimes referred to as visceral adipose tissue, or VAT, as a cardiovascular disease risk marker. VAT is commonly determined by waist circumference, the ratio of waist circumference to height (taking body size into account) or waist-to-hip ratio, which has been shown to predict cardiovascular death independent of BMI.
Experts recommend both abdominal measurement and BMI be assessed during regular health care visits because a high waist circumference or low waist-to-hip ratio, even in healthy weight individuals, could mean an increased risk of heart disease. Abdominal obesity is also linked to fat accumulation around the liver that often leads to non-alcoholic fatty liver disease, which adds to cardiovascular disease risk.
“Studies that have examined the relationship between abdominal fat and cardiovascular outcomes confirm that visceral fat is a clear health hazard,” said Powell-Wiley.
The risk-inducing power of abdominal obesity is so strong that in people who are overweight or have obesity based on BMI, low levels of fat tissue around their midsection and organs could still indicate lower cardiovascular disease risks. This concept, referred to as “metabolically healthy obesity,” seems to differ depending on race/ethnicity and sex.

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Membranes unlock potential to vastly increase cell-free vaccine production

By cracking open a cellular membrane, Northwestern University synthetic biologists have discovered a new way to increase production yields of protein-based vaccines by five-fold, significantly broadening access to potentially lifesaving medicines.
In February, the researchers introduced a new biomanufacturing platform that can quickly make shelf-stable vaccines at the point of care, ensuring they will not go to waste due to errors in transportation or storage. In its new study, the team discovered that enriching cell-free extracts with cellular membranes — the components needed to made conjugate vaccines — vastly increased yields of its freeze-dried platform.
The work sets the stage to rapidly make medicines that address rising antibiotic-resistant bacteria as well as new viruses at 40,000 doses per liter per day, costing about $1 per dose. At that rate, the team could use a 1,000-liter reactor (about the size of a large garden waste bag) to generate 40 million doses per day, reaching 1 billion doses in less than a month.
“Certainly, in the time of COVID-19, we have all realized how important it is to be able to make medicines when and where we need them,” said Northwestern’s Michael Jewett, who led the study. “This work will transform how vaccines are made, including for bio-readiness and pandemic response.”
The research will be published April 21 in the journal Nature Communications.
Jewett is a professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and director of Northwestern’s Center for Synthetic Biology. Jasmine Hershewe and Katherine Warfel, both graduate students in Jewett’s laboratory, are co-first authors of the paper.
The new manufacturing platform — called in vitro conjugate vaccine expression (iVAX) — is made possible by cell-free synthetic biology, a process in which researchers remove a cell’s outer wall (or membrane) and repurpose its internal machinery. The researchers then put this repurposed machinery into a test tube and freeze-dry it. Adding water sets off a chemical reaction that activates the cell-free system, turning it into a catalyst for making usable medicine when and where it’s needed. Remaining shelf-stable for six months or longer, the platform eliminates the need for complicated supply chains and extreme refrigeration, making it a powerful tool for remote or low-resource settings.
In a previous study, Jewett’s team used the iVAX platform to produce conjugate vaccines to protect against bacterial infections. At the time, they repurposed molecular machinery from Escherichia coli to make one dose of vaccine in an hour, costing about $5 per dose.
“It was still too expensive, and the yields were not high enough,” Jewett said. “We set a goal to reach $1 per dose and reached that goal here. By increasing yields and lowering costs, we thought we might be able to facilitate greater access to lifesaving medicines.”
Jewett and his team discovered that the key to reaching that goal lay within the cell’s membrane, which is typically discarded in cell-free synthetic biology. When broken apart, membranes naturally reassemble into vesicles, spherical structures that carry important molecular information. The researchers characterized these vesicles and found that increasing vesicle concentration could be useful in making components for protein therapeutics such as conjugate vaccines, which work by attaching a sugar unit — that is unique to a pathogen — to a carrier protein. By learning to recognize that protein as a foreign substance, the body knows how to mount an immune response to attack it when encountered again.
Attaching this sugar to the carrier protein, however, is a difficult, complex process. The researchers found that the cell’s membrane contained machinery that enabled the sugar to more easily attach to the proteins. By enriching vaccine extracts with this membrane-bound machinery, the researchers significantly increased yields of usable vaccine doses.
“For a variety of organisms, close to 30% of the genome is used to encode membrane proteins,” said study co-author Neha Kamat, who is an assistant professor of biomedical engineering at McCormick and an expert on cell membranes. “Membrane proteins are a really important part of life. By learning how to use membrane proteins effectively, we can really advance cell-free systems.”
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Materials provided by Northwestern University. Original written by Amanda Morris. Note: Content may be edited for style and length.

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Average-risk individuals may prefer stool-based test over colonoscopy for cancer screening

Although colorectal cancer is the second most frequent cause of cancer-related death in the United States, about one-third of eligible American adults have never completed a colorectal cancer screening test, explained lead author Zhu. Zhu added that colorectal cancer screening is particularly underutilized by individuals experiencing socioeconomic disadvantages, racial and ethnic minorities, and certain age groups.
The U.S. Preventive Services Task Force (USPSTF) recommends several colorectal cancer screening methods for adults ages 50 to 75 with an average risk for this disease, and the USPSTF draft guideline update released in October 2020 recommends lowering the age of screening initiation to 45. The three most common tests are an annual fecal immunochemical test or fecal occult blood test (FIT/FOBT) that detects blood in the stool; the multitarget stool DNA (mt-sDNA) test (Cologuard), completed every three years, which detects altered DNA from cancer cells, precancerous polyps, or blood in the stool; and a colonoscopy every 10 years, which involves a gastroenterologist examining the colon with a camera and removing any precancerous polyps while a patient is under sedation.
“Previous research has shown that fewer patients complete colorectal cancer screening when only colonoscopy is recommended compared to when stool-based options are also recommended,” said Zhu.
In this study, Zhu and colleagues evaluated patient preferences for colorectal cancer screening through a survey conducted in collaboration with the National Opinion Research Center at the University of Chicago. The survey included short descriptions of FIT/FOBT, mt-sDNA, and colonoscopy, and asked a nationally representative sample of adults ages 40 to 75 to choose between two options presented at a time. A total of 1,595 respondents completed the survey. The researchers focused their analysis on a subgroup of 1,062 respondents aged 45 to 75 with an average risk of colorectal cancer.
When presented with a choice, 66 percent of respondents said they preferred mt-sDNA over colonoscopy, and 61 percent said they preferred FIT/FOBT over colonoscopy. When asked to choose between the two stool-based options, 67 percent indicated a preference for mt-sDNA over FIT/FOBT.
The investigators also examined differences in patient preferences across sociodemographic characteristics, access to health care, awareness of colorectal cancer screening, and prior experience completing a test. While mt-sDNA was preferred over colonoscopy for all age groups examined, a larger proportion of older adults (ages 65 to 75 years) said they preferred colonoscopy compared to those in younger age groups (ages 45 to 54 years).
Similarly, the preference for mt-sDNA over colonoscopy was higher among non-Hispanic white individuals compared with non-Hispanic Black and Hispanic individuals. Half of Hispanic and non-Hispanic Black respondents preferred stool-based tests over colonoscopy, with a preference for mt-sDNA over FIT/FOBT. Zhu said the observed differences among age and racial/ethnic groups might have reflected variations in preferences or disparities in access to information about newer testing methods.
Respondents without insurance were 2.5 times more likely to prefer less expensive stool-based tests over colonoscopy. The overall awareness of stool-based tests was about 60 percent, compared to 90 percent for colonoscopy, indicating that there is an opportunity to improve patient education about stool-based options, Zhu noted. Study participants who were aware of stool-based tests were two times more likely to prefer mt-sDNA over FIT/FOBT, and those who had previously had a stool-based test were 2.8 times more likely to choose FIT/FOBT over colonoscopy. By contrast, those who had previously had a colonoscopy were less than half as likely to prefer a stool-based test over colonoscopy and those who had a provider recommend colonoscopy in the past 12 months were 40 percent less likely to prefer mt-sDNA over colonoscopy.
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Materials provided by American Association for Cancer Research. Note: Content may be edited for style and length.

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Study Demonstrates Saliva Can Spread Novel Coronavirus

Caption: SARS-CoV-2 (pink) and its preferred human receptor ACE2 (white) were found in human salivary gland cells (outlined in green). Credit: Paola Perez, Warner Lab, National Institute of Dental and Craniofacial Research, NIH

COVID-19 is primarily considered a respiratory illness that affects the lungs, upper airways, and nasal cavity. But COVID-19 can also affect other parts of the body, including the digestive system, blood vessels, and kidneys. Now, a new study has added something else: the mouth.

The study, published in the journal Nature Medicine, shows that SARS-CoV-2, which is the coronavirus that causes COVID-19, can actively infect cells that line the mouth and salivary glands. The new findings may help explain why COVID-19 can be detected by saliva tests, and why about half of COVID-19 cases include oral symptoms, such as loss of taste, dry mouth, and oral ulcers. These results also suggest that the mouth and its saliva may play an important—and underappreciated—role in spreading SARS-CoV-2 throughout the body and, perhaps, transmitting it from person to person.

The latest work comes from Blake Warner of NIH’s National Institute of Dental and Craniofacial Research; Kevin Byrd, Adams School of Dentistry at the University of North Carolina, Chapel Hill; and their international colleagues. The researchers were curious about whether the mouth played a role in transmitting SARS-CoV-2. They were already aware that transmission is more likely when people speak, cough, and even sing. They also knew from diagnostic testing that the saliva of people with COVID-19 can contain high levels of SARS-CoV-2. But did that virus in the mouth and saliva come from elsewhere? Or, was SARS-CoV-2 infecting and replicating in cells within the mouth as well?

To find out, the research team surveyed oral tissue from healthy people in search of cells that express the ACE2 receptor protein and the TMPRSS2 enzyme protein, both of which SARS-CoV-2 depends upon to enter and infect human cells. They found the proteins to be expressed individually in the primary cells of all types of salivary glands and in tissues lining the oral cavity. Indeed, a small portion of salivary gland and gingival (gum) cells around our teeth, simultaneously expressed both ACE2 and TMPRSS2.

Next, the team detected signs of SARS-CoV-2 in just over half of the salivary gland tissue samples that it examined from people with COVID-19. The samples included salivary gland tissue from one person who had died from COVID-19 and another with acute illness.

The researchers also found evidence that the coronavirus was actively replicating to make more copies of itself. In people with mild or asymptomatic COVID-19, oral cells that shed into the saliva bathing the mouth were found to contain RNA for SARS-CoV-2, as well its proteins that it uses to enter human cells.

The researchers then collected saliva from another group of 35 volunteers, including 27 with mild COVID-19 symptoms and another eight who were asymptomatic. Of the 27 people with symptoms, those with virus in their saliva were more likely to report loss of taste and smell, suggesting that oral infection might contribute to those symptoms of COVID-19, though the primary cause may be infection of the olfactory tissues in the nose.

Another important question is whether SARS-CoV-2, while suspended in saliva, can infect other healthy cells. To get the answer, the researchers exposed saliva from eight people with asymptomatic COVID-19 to healthy cells grown in a lab dish. Saliva from two of the infected volunteers led to infection of the healthy cells. These findings raise the unfortunate possibility that even people with asymptomatic COVID-19 might unknowingly transmit SARS-CoV-2 to other people through their saliva.

Overall, the findings suggest that the mouth plays a greater role in COVID-19 infection and transmission than previously thought. The researchers suggest that virus-laden saliva, when swallowed or inhaled, may spread virus into the throat, lungs, or digestive system. Knowing this raises the hope that a better understanding of how SARS-CoV-2 infects the mouth could help in pointing to new ways to prevent the spread of this devastating virus.

Reference:

[1] SARS-CoV-2 infection of the oral cavity and saliva. Huang N, Pérez P, Kato T, Mikami Y, Chiorini JA, Kleiner DE, Pittaluga S, Hewitt SM, Burbelo PD, Chertow D; NIH COVID-19 Autopsy Consortium; HCA Oral and Craniofacial Biological Network, Frank K, Lee J, Boucher RC, Teichmann SA, Warner BM, Byrd KM, et. al Nat Med. 2021 Mar 25.

Links:

COVID-19 Research (NIH)

Saliva & Salivary Gland Disorders (National Institute of Dental and Craniofacial Research/NIH)

Blake Warner (National Institute of Dental and Craniofacial Research/NIH)

Kevin Byrd (Adams School of Dentistry at University of North Carolina, Chapel Hill)

NIH Support: National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases

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