Publisher Health

Elevated levels of an enzyme called PHGDH in the blood of older adults could be an early warning sign of Alzheimer’s disease, and a study led by the University of California San Diego provides new evidence to support this claim. In analyzing brain tissue, researchers observed a trend consistent with their previous findings in blood samples: expression levels of the gene coding for PHGDH were consistently higher in adults with different stages of Alzheimer’s disease, even the early stages before cognitive symptoms manifested.
The findings also prompt caution against the use of dietary supplements that contain the amino acid serine as a remedy for Alzheimer’s disease. Because PHGDH is a key enzyme in the production of serine, the increased PHGDH expression found in Alzheimer’s patients suggests that the rate of serine production in the brain is also increased, and thus, taking additional serine may not be beneficial, the researchers warned.
Researchers led by Sheng Zhong, a professor of bioengineering at the UC San Diego Jacobs School of Engineering, and Xu Chen, a professor of neurosciences at UC San Diego School of Medicine, published their findings May 3 in Cell Metabolism.
The new study builds on earlier work by Zhong and colleagues that first identified PHGDH as a potential blood biomarker for Alzheimer’s disease. The researchers had analyzed blood samples of older adults and found a steep increase in PHGDH gene expression in Alzheimer’s patients, as well as in healthy individuals approximately two years before they were diagnosed with the disease.
The results were promising, and the researchers were curious if this increase could be linked back to the brain. In their new study, they show that this indeed is the case.
“It’s exciting that our previous discovery of a blood biomarker is now corroborated with brain data,” said Zhong. “Now we have strong evidence that the changes we see in human blood are directly correlated to changes in the brain in Alzheimer’s disease.”
The researchers analyzed genetic data collected from post-mortem human brains from subjects in four different research cohorts, each made up of 40 to 50 individuals 50 years and older. The subjects consisted of Alzheimer’s patients, so-called “asymptomatic” individuals (people without cognitive problems and without an Alzheimer’s diagnosis, but whose post-mortem brain analyses showed early signs of Alzheimer’s-related changes), and healthy controls.

Are astronauts more likely to develop blood clots during space missions due to zero gravity? That’s the question NASA is trying to answer with help from UNC School of Medicine’s Stephan Moll, MD, professor in the UNC Department of Medicine. A new publication in Vascular Medicine shows the results of an occupational surveillance program spurred by the development of a deep vein thrombosis (DVT) in the jugular vein of an astronaut, which is described in detail in a New England Journal of Medicine publication from 2020.
Moll was consulted by NASA when the discovery of the blood clot was made during the astronaut’s mission on the International Space Station (ISS). This was the first time a blood clot had been found in an astronaut in space, so there was no established method of treatment for DVT in zero gravity. Moll, a member of the UNC Blood Research Center and a clinical hematologist, was called upon for his knowledge and treatment experience of DVT on Earth. In the ultimate act of telemedicine, Moll and NASA physicians helped treat the astronaut over several months, until they safely returned to Earth.
This astronaut’s blood clot was asymptomatic — they didn’t have any symptoms that would have otherwise indicated there was a clot. The DVT was discovered when the astronaut was taking ultrasounds of their own neck for a research study on how body fluid is redistributed in zero gravity. If it wasn’t for the study, there’s no telling what the outcome could have been. That’s why Moll has continued to work with NASA to research how blood flow and blood clots behave in space.
“I’ve always been a space enthusiast,” Moll said. “When I was young I wanted to be an astronaut, so when NASA called on me to help, it was pretty incredible. And it’s been amazing to then continue working with NASA doing research on blood clots in space that will help develop the health and safety protocols for future space travel.”
Moll and fellow researchers, led by NASA’s James Pavela, MD, monitored 11 astronauts over a combined total of 2,150 days in zero gravity on the ISS. All astronauts were evaluated before leaving Earth to get a baseline of their blood flow and blood vessel size in the veins of their neck. Once in space, astronauts performed ultrasounds on their own necks with guidance from a radiology team on Earth to monitor any changes that occurred in zero gravity.
“We expected some changes in flow based on the absence of gravity,” Moll said. “Gravity pulls fluid in your body down. It also creates a force on your blood vessels and this increased pressure in the veins of the legs leads to leakage of fluid from the blood vessels into the soft tissues. You can notice this when you stand for a long time and develop swelling in your ankles, feet, and sometimes hands.
“Without gravity, fluids like blood redistribute in your body. When astronauts arrive in space, the lack of gravity causes the blood vessels in the neck to expand due to fluid shifting to the upper part of the body. Astronauts develop swelling of the neck and face from this shift. That is a normal and expected finding.”
The question Moll and NASA wanted to answer is if this difference in flow and vessel size could put astronauts at risk for the development of blood clots. While abnormal flow characteristics were recorded in six of the eleven astronauts, none developed blood clots. However, the findings of slowed blood flow in the neck veins, abnormal echo findings on the examination, and even reversal of blood flow in two astronauts raises the question whether these abnormalities could predispose these space travelers to blood clots.
Because this was a small study, researchers cannot make firm conclusions. Moll says more research is needed, but due to the challenges of such investigations and the small pool of astronauts to participate in future studies, it may take some time to draw definite conclusions.
In the meantime, this research helps inform what medical supplies, like blood thinners, should be available for current and future spaceflight missions. The data will also help guide the use and development of interventions designed to minimize the potentially increased blood clot risk of spaceflight.
This study was funded by NASA.

CT-detected emphysema is linked to a higher risk of lung cancer, a risk that increases with emphysema severity, according to a new study published in the journal Radiology.
Lung cancer is the primary cause of cancer-related death worldwide, with more than 1 million deaths each year since 2000. However, lung cancer risk can be reduced by identifying treatable risk factors, such as chronic lung inflammation, together with smoking, genetics, diet, and occupational exposure.
Emphysema is a chronic respiratory disease characterized by damage to the alveoli, the tiny air sacs inside the lungs. Symptoms include shortness of breath, coughing with mucus, wheezing and chest tightness. There is no cure, but many treatments are available to help manage symptoms.
Emphysema shares many common risk factors with lung cancer, the leading cause of cancer-related deaths worldwide.
Cigarette smoking is one of the important shared risk factors of emphysema and lung cancer, as it enhances inflammation, DNA damage and accelerated aging. However, people with emphysema who’ve never smoked also have an increased risk of lung cancer, according to study co-author Marleen Vonder, Ph.D., from the Department of Epidemiology at University Medical Center Groningen in Groningen, the Netherlands.
“Other underlying mechanisms like genetic susceptibility, chronic inflammation or DNA damage and abnormal repair mechanisms, or a combination thereof, have been proposed to link emphysema and lung cancer,” she said.
For the new study, Dr. Vonder and colleagues identified studies from three large databases on the association between emphysema and lung cancer. Analysis of 21 studies involving more than 107,000 patients found a connection between visual and quantitative, or measurable, CT assessments of emphysema and lung cancer.
“Our meta-analysis showed that not only visually assessed but also quantitatively assessed emphysema on CT is associated with lung cancer and that this risk increases for more severe emphysema,” Dr. Vonder said.
While the findings support a link between the two devastating diseases, more research is needed before any changes are made to clinical care, Dr. Vonder said.
“It is too early to conclude whether the presence of CT-defined emphysema leads to incremental and independent prognostic value over that of already known shared risk factors of emphysema and lung cancer,” she said.
The associations between CT emphysema and lung cancer were higher for categories of visual assessment compared to quantitative assessment. Despite this finding, Dr. Vonder said that quantitative assessment may ultimately gain favor over visual assessment, as it can be fully automated. She and her colleagues are researching this approach and validating its use in specified populations.
“Potentially, emphysema detected on a baseline CT scan could be used to select high-risk participants who would require more frequent follow-up lung cancer screening,” Dr. Vonder said.

Officials are exploring the possibility that a common adenovirus might be responsible for the unexplained cases, which remain rare.At least 16 countries and 10 U.S. states have either identified or are investigating reports of unusual hepatitis cases in otherwise healthy children.The cases remain extremely rare, with about 200 children affected worldwide, according to a report issued last week by the European Centre for Disease Prevention and Control.But even these small clusters are unusual. In Britain, where most of the cases have been reported, two pediatric liver units have already had at least as many admissions for acute, unexplained hepatitis in 2022 as they typically have in an entire year, according to a briefing from the U.K. Health Security Agency.Most children should recover fully, experts said, but some cases have been severe. In nearly 10 percent of reported cases, children have required liver transplants, according to the World Health Organization. There has been at least one death, the W.H.O. said.The cause remains unknown, but scientists are exploring the possibility that an adenovirus may be responsible. Adenoviruses are common, but they are not usually associated with hepatitis in healthy children. And with many nations only now beginning to look for cases in earnest, the scope of the problem remains unknown.“It’s still early days,” said Dr. Richard Malley, an infectious disease specialist at Boston Children’s Hospital. “It’s hard to predict whether this will become more common or if, in fact, it will just be a blip in our 2022 infectious-disease story.”Here’s what scientists know so far.What is hepatitis?Hepatitis is an inflammation of the liver and can have a wide range of causes. Viral infections can cause the condition; the viruses known as hepatitis A, B, C, D and E are all known triggers.Understanding HepatitisAn inflammation of the liver generally caused by a virus, hepatitis carries a host of complicating factors, side effects and stigma. Personal Accounts: What is it like to live with the disease? Six individuals shared their experience. Symptoms in Children: Hepatitis symptoms in children overlap with many common illnesses. Here are the warning signs parents should watch out for.Preventing Transmission: With infections on the rise, most adults should be getting screened for hepatitis.Pandemic’s Effect: A wave of diagnostics ushered in by Covid could help revive flagging efforts to eliminate hepatitis C, one of the most common forms of the disease.Heavy drinking, as well as certain medications and toxic substances, can also cause hepatitis. In autoimmune hepatitis, the body’s own immune system attacks the liver.Sudden and severe hepatitis in previously healthy children is uncommon, which is why the new clusters of cases have prompted concern.Where have the new cases been reported?In early April, Britain became the first country to notify the W.H.O. of a cluster of unexplained hepatitis cases in children. The cases were unusual because they occurred over a short period of time in otherwise healthy children, and because clinicians quickly ruled out any of the common hepatitis viruses as the cause. They did not identify any patterns in travel, diet, chemical exposures or other risk factors that might explain the outbreak, according to the U.K. Health Security Agency’s briefing.Since then, Austria, Belgium, Denmark, France, Germany, Ireland, Israel, Italy, Japan, the Netherlands, Norway, Poland, Romania, Spain and the United States have reported similar cases, the E.C.D.C. said.In the United States, Alabama recorded nine cases between October and February. Three of the children developed liver failure, and two required liver transplants, the Centers for Disease Control and Prevention noted in a recent report. All of the children either recovered or are recovering, the agency noted.“The two that received the transplant are actually doing quite well,” said Dr. Henry Shiau, a pediatric transplant hepatologist at the University of Alabama at Birmingham and the Children’s of Alabama hospital.The cases prompted the C.D.C. to issue a nationwide alert, asking health care providers to keep an eye out for similar cases.Illinois and Wisconsin have since announced potential cases. North Carolina, Delaware, Minnesota, California, New York, Georgia and Louisiana have also identified, or are investigating, possible cases, state officials told The New York Times.What are the symptoms?In many of the cases, children developed gastrointestinal symptoms, including vomiting, diarrhea and abdominal pain, followed by a yellowing of the skin or eyes, known as jaundice. They also had abnormally high levels of liver enzymes, a sign of liver inflammation or damage.Gastrointestinal symptoms are common in children and should not, in isolation, be cause for alarm, Dr. Shiau said. But a yellowing of the skin or eyes are more telltale signs of liver problems, he said.“The likelihood of your child developing hepatitis is extremely low,” Dr. Meera Chand, the director of clinical and emerging infections at the U.K. Health Security Agency, said in a statement. “However, we continue to remind parents to be alert to the signs of hepatitis — particularly jaundice, which is easiest to spot as a yellow tinge in the whites of the eyes — and contact your doctor if you are concerned.”What’s causing it?“That’s the million-dollar question,” Dr. Shiau said. “I want to be up front about this: We don’t know.”But one leading hypothesis is that an adenovirus — one of a group of common viruses that often cause cold-like symptoms — is responsible. Of the 169 cases included in a recent W.H.O. report, at least 74 had an adenovirus infection, the organization said. Eighteen of those children were infected with what is known as adenovirus type 41, which typically causes gastrointestinal and respiratory symptoms.Adenovirus infections have been on the rise in Britain, where most of the hepatitis cases have been reported, the W.H.O. said.But the explanation is not a perfect fit. Not all of the children have tested positive for an adenovirus, and while the viruses can cause liver inflammation, that symptom is most common in people who are immunocompromised. “It is not a common cause of liver failure in kids,” said Dr. Aaron Milstone, a pediatric infectious diseases specialist at Johns Hopkins Children’s Center.It is possible that a new adenovirus strain has emerged or that adenovirus infections are occurring in conjunction with some other risk factor — such as a toxic exposure or an infection with another pathogen — causing these unusually severe outcomes, the U.K. Health Security Agency said.Or the adenovirus infections could be a red herring. Because the viruses are so common among children, it is difficult to determine whether they are the cause of these hepatitis cases or whether many of the children have been infected incidentally. “Somebody could be infected with adenovirus and then develop hepatitis based on something else,” Dr. Malley said. “For proof of causality you really need a lot of data, which we just don’t have.”Is this connected to Covid-19?Probably not directly, experts said. Of the 169 patients identified by the W.H.O., 20 tested positive for the coronavirus. That is not surprising, given how widely the virus has been spreading in recent months, scientists said.And there is no evidence that the hepatitis is linked to the Covid-19 vaccines; the “vast majority” of the children in question had not been vaccinated, the W.H.O. said.Still, a coronavirus connection cannot be entirely ruled out, experts cautioned, and the hepatitis cases may be linked to the pandemic in less direct ways. For example, the public health measures implemented over the past two years may have left fewer children exposed to common adenoviruses. That, in turn, might have made them more susceptible now, according to one of the U.K. Health Security Agency’s working hypotheses.But that, too, is speculative.“At this point,” Dr. Shiau said, “we still don’t know what’s going on.”

Extending your vacation as you wait for negative test results — it’s a luxurious thought. But the reality can be expensive and stressful. Here’s what you need to know.As coronavirus travel restrictions ease across many parts of the world and countries report cases of less severe illness, international trips are top of mind for U.S. travelers, many of whom have started to book overseas journeys for the spring and summer.But the requirement for air travelers — vaccinated or not — to present a negative coronavirus test for entry into the United States has many people concerned about the prospect of testing positive and finding themselves stuck in a foreign country, unable to return home.Deborah Haines, 47, a chiropractor from Seattle, was forced to extend her vacation in the Netherlands by 22 days last month because she kept testing positive even after her coronavirus symptoms had subsided. The stress of determining the appropriate documentation for re-entry, and having to cancel work appointments back home, made her feel sicker than the coronavirus itself, she said.“When I thought about the possibility of getting stuck with Covid in Amsterdam, I thought it would mean a few extra days and then I could get a negative test and go home,” she said. “Boy, was that a miscalculation. I kept testing positive and it was so hard to get any clear guidance for what I should do.”For months, the travel industry has been lobbying Washington to drop pandemic measures like mask mandates and testing requirements for travelers. A federal judge in Florida struck down the mask mandate on public transportation in April, allowing airlines and other transit authorities to set their own mask policies. The Biden administration has appealed. But it has not commented recently on the status of pre-departure testing, with the White House coronavirus response coordinator, Jeff Zients, announcing on April 5 that there were “no plans to change international travel requirements at this point.”The uncertainty over the travel rules is making it difficult for travelers to book international trips with confidence. Here’s how to navigate some of the challenges you might face if you test positive abroad.Time to head home. Remind me of the test requirements?To enter the United States, all air passengers age 2 and older must have a negative coronavirus test taken within one day of departure, regardless of their vaccination status.The accepted PCR and viral tests are available at many hotels, airports, health clinics and local pharmacies overseas. Certain antigen or nucleic acid amplification self-tests like BinaxNOW and Ellume that have been approved for emergency use by the Food and Drug Administration are also accepted. These require you to connect to a telehealth service by video, so that you can be supervised by a medical practitioner while you take the test; make sure you have a good internet connection.There are no testing requirements for travelers entering the United States through land or ferry ports of entry.I’m positive! Do I need to self-isolate or quarantine?If you test positive, the Centers for Disease Control and Prevention recommends you should isolate and delay travel for 10 days, regardless of symptoms or a negative test taken within the isolation period. The country where you are staying may have its own rules for quarantine and isolation. The rules differ from country to country and isolation periods may be longer than the 10 days recommended by the C.D.C. Across Europe, many countries follow guidance from the European Center for Disease Prevention and Control, which recommends that fully vaccinated people should self-isolate after testing positive. If their symptoms improve and they feel better for at least 24 hours and they test negative for the virus twice within a 24-hour period, they can stop isolating. Or, if after six days they test negative once, they can stop isolating. Unvaccinated people are advised to self-isolate for 10 days, but can leave isolation if they meet the same requirements for negative tests. Some other destinations, particularly in Asia, may require mandatory quarantine or isolation in a government facility or designated hotel for 14 days or more.Am I required to tell government officials that I’m positive?This will depend on the regulations in the country you are visiting, so be sure to check what they say on local health ministry websites. In most places, tourists are not required to officially report a positive test result to the government, although if you took your test in person at a local health facility, the results are often sent to the regional or national health authority.Where can I stay if I have to isolate?Most countries, including popular European destinations like Greece, Italy and France, allow visitors testing positive to choose their own accommodation for the recommended period of self-isolation. You can find this information on U.S. embassy websites. If you have booked a hotel or Airbnb for your trip, it is worth calling ahead of time and seeing what their policy is for isolation and whether they have availability should you need to extend your stay.Some lodging facilities will require you to isolate alone in a separate room, even if your family members or travel companions test negative. You should also ask about access to food and medical facilities, particularly if you are staying in a remote area.It’s useful to have a plan B in place in case your hotel or rental cannot accommodate you, or to have a cheaper option available if you do have to self-isolate for 10 days. Many countries have designated “quarantine hotels” or apartments and some resorts in popular tourist destinations like Spain, Portugal and Mexico allow guests to quarantine at a discounted rate.Feeling fine, yet still positive. What now?While most people are likely to test negative within 10 days of a positive coronavirus test, for some it can take weeks or even months, according to the global health partnership Gavi, the Vaccine Alliance. If you find yourself in that position, and feel well enough to travel, you can return to the United States but will need to obtain “documentation of recovery.”For this documentation, there are six pieces of information you must provide:The type of coronavirus test you took.Evidence of positive results (“invalid” or “inconclusive” results are not accepted).Your name on the test results, which must match your identification.Where the test was taken, such as the name of the clinic or laboratory. If you self-tested, you can supply the brand name.The date the test was taken, which must be within the last 90 days.The test result must be accompanied by a letter signed by a licensed health care provider or a public health official stating that you have recovered and have been cleared to travel. This can be your health care provider in the United States.More information can be found on the C.D.C.’s airline checklist.Some American doctors are not authorized to provide the documentation outside of the United States or are unable to issue it to you because they need to see you in person. In those cases, Americans have been using telemedicine services like Quick MD, which involves a video or telephone consultation with a doctor, to obtain the documents, or they have booked in-person consultations with a local medical practitioner. Expect to pay $75 for QuickMD, and between $50 and $250 for a local doctor.Ms. Haines, the chiropractor who got stuck in the Netherlands, tested positive for the virus a day before she was scheduled to fly home in March. She immediately extended her apartment booking in Amsterdam for 11 days, but in a frenzy to rearrange her work commitments, she forgot to reschedule her flight.“I had thought about the possibility that I might test positive before I booked my trip, but didn’t think it would actually happen and that’s why I didn’t have a thought-out plan,” she said. “It was very high stress trying to figure everything and eventually I got Covid symptoms, which were pretty rough.”Ms. Haines kept testing positive for the virus, even after her 10-day isolation period. After 17 days, with help from her husband back home, she managed to get a certificate of recovery through a U.S. telemedicine service that she found online. She waited a few more days to fly home because she had to purchase a new flight and went for the cheapest option.“That process was pretty straightforward in the end,” she said. “But before that, we hit so many obstacles and dead ends and felt really stuck.”Will my airline accept my document of recovery?Most airlines flying to the United States accept paperwork that meets the C.D.C.’s requirements for documentation of recovery. If you are traveling through a third country and plan to leave the airport, however, check the local guidance as some governments may require a longer period of isolation or have other restrictions.“Understand the rules for the country you’re departing from and understand that those rules may change,” said Erika Richter, the senior communications director of the American Society of Travel Advisors, a trade organization. “Travelers should plan to bring with them printed copies of all their paperwork so they can present it to the gate agency,” she said. “You’re really at the mercy of the gate agent upon check-in, so keep that in mind.”Some travelers have also found it useful to print out the C.D.C. guidelines for certificates of recovery to present to the gate agent, she added.Will travel insurance cover additional costs if I test positive?It depends on the type of insurance. The U.S. Travel Insurance Association recommends that travelers concerned about the potential disruption to their plans after testing positive should investigate policies that include sickness and quarantine coverage, and also determine if there are any limits to those benefits.Some policies will cover lodging costs beyond your scheduled return date but may not cover the full 10 days you are required to isolate (you can compare policies on review sites like Covertrip). If you are worried that you could get stuck for even longer as you try to obtain a certificate of recovery, then you might want to opt for a higher level of coverage.Many travel insurance plans cover the costs to see a physician in order to obtain the documentation of recovery under medical expense, trip interruption or travel delay, according to the Travel Insurance Association. Under most policies, trip interruption coverage also covers charges for flight change fees.But travelers should understand that plans often have a daily maximum trip delay limit, and the policy may not cover all costs associated with an extended stay, according to the association.52 Places for a Changed WorldThe 2022 list highlights places around the globe where travelers can be part of the solution.Follow New York Times Travel on Instagram, Twitter and Facebook. And sign up for our weekly Travel Dispatch newsletter to receive expert tips on traveling smarter and inspiration for your next vacation. Dreaming up a future getaway or just armchair traveling? Check out our 52 Places for a Changed World for 2022.

Per- and polyfluoroalkyl substances (PFAS) and phthalates (two types of endocrine-disrupting chemicals) may be associated with lower bone mineral density in male teens, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology and Metabolism.
Endocrine-disrupting chemicals are chemicals or mixtures of chemicals that interfere with the way the body’s hormones work. Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in nonstick cookware, clothing and food packaging, and are increasingly being found in U.S. water supplies. Phthalates are used in personal care products, food processing and children’s toys.
“Adolescence is an important time when our bodies build up bone. Almost all U.S. children and adolescents are exposed to PFAS and phthalates, but few studies have looked at how these chemicals could be impacting our bone health,” said Abby F. Fleisch, M.D., M.P.H., of the Maine Medical Center Research Institute and Maine Medical Center in Portland, Maine. “Our research found an association between certain PFAS and phthalates and reduced bone mineral density in adolescent males. Because bone accrual primarily occurs during adolescence, if replicated, this finding may have implications for lifelong bone health.”
The researchers leveraged urine and blood samples from 453 boys and 395 girls from the National Health and Nutrition Examination Survey (NHANES) and found higher levels of PFAS and phthalates may be associated with lower bone mineral density in adolescent males. The researchers did not find the same effect in girls.
Other authors of this study include: Jenny L. Carwile, Shravanthi M. Seshasayee and Clifford J. Rosen of the Maine Medical Center Research Institute; Katherine A. Ahrens of the University of Southern Maine in Portland, Maine; Russ Hauser of the Harvard T. H. Chan School of Public Health in Boston, Mass.; Jeffrey B. Driban of the Tufts Medical Center in Boston, Mass.; and Catherine M. Gordon of the Texas Children’s Hospital and Baylor College of Medicine in Houston, Texas.
The study received funding from the National Institute of Environmental Health Sciences.
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Materials provided by The Endocrine Society. Note: Content may be edited for style and length.

UVA Health researchers and their collaborators have developed a better way to predict the risk of chronic obstructive pulmonary disease (COPD), a progressive, potentially deadly form of lung inflammation, for people of non-European ancestry.
Initial tests of the new, more inclusive tool revealed that it is better at predicting COPD risk for both African-Americans and heavy smokers than existing models that were based on genetic information largely collected from people of European ancestry. The tool’s developers say their approach will allow doctors to better predict COPD risk for individuals of diverse ancestry in the United States and around the world.
“Our study demonstrates the possibility of learning from large-scale genetic studies performed primarily in European ancestry groups, and then developing prediction models that can be used for prediction of genetic risk in other ancestry groups,” said researcher Ani W. Manichaikul, PhD, of the University of Virginia School of Medicine. “While the current study focus on risk prediction for COPD, we are already looking to apply similar approaches to improve prediction of genetic risk for other diseases.”
About COPD
While treatable, COPD is a leading cause of death in the United States and around the globe. Approximately 16 million Americans have COPD, which is a group of lung conditions that includes emphysema and chronic bronchitis. The lung damage caused by COPD is irreversible and accumulates over time. That makes early detection and treatment especially important.
In recent years, doctors have been able to predict patients’ genetic risk of developing COPD and other common diseases using what are called “polygenic risk scores,” or PRS. These look at the total number of naturally occurring gene variations a person has that predispose them to a disease — in this case, COPD. To date, most large-scale genetic studies available for the study of disease risk have limited representation of certain ancestry groups, including African-American and Hispanic, yielding poorer prediction of disease risk for these groups.
Manichaikul and her collaborators sought to improve the ability to predict COPD by better reflecting the world’s genetic diversity. To do so, they layered genetic measurements with other molecular measures from a diverse ancestry group that included a combination of European ancestry, African-American and Hispanic individuals from the United States. Building on these resources, they developed what they call “PrediXcan-derived polygenic transcriptome risk score,” or PTRS. This new approach incorporates much more information about the cumulative effects of gene variations in different groups of people. The result is a model that “bears a more direct connection to underlying disease biology than standard PRS approaches,” the researchers report in a new scientific paper.
The scientists put their new tool to the test by analyzing its ability to predict COPD in tens of thousands of participants in studies conducted by the Trans-Omics for Precision Medicine (TOPMed) program sponsored by the National Institutes of Health’s National Heart, Lung and Blood Institute (NHLBI).
PTRS, they found, was better at predicting COPD in African-Americans and better at predicting moderate to severe COPD in heavy, longtime smokers. Perhaps unsurprisingly (considering it was developed to better reflect non-European populations), PTRS was less effective than PRS in predicting COPD in people of European ancestry. But the availability of multiple “crystal balls” to predict COPD in different populations moves us an important step closer to true precision medicine — medicine tailored to each individual.
“So far, we have shown that by building on genomic data combined with gene expression data from diverse ancestry individuals, we can improve prediction of genetic risk for some people,” said Manichaikul, of UVA’s Center for Public Health Genomics and Department of Public Health Sciences. “Looking forward, we are excited to think about how we can build on other collections of molecular data from diverse ancestry individuals and keep working on improved approaches for prediction of genetic risk for other diseases.”
The work was funded by NHLBI grants R01 HL131565, R01 HL153248, R01 HL135142, R01 HL137927, R01 HL089856, R01 HL147148 and K01-HL129039.

Just mentioning a ruptured Achilles tendon would make anyone wince. Tendon injuries are well known for their lengthy, difficult and often incomplete healing processes. Sudden or repetitive motion, experienced by athletes and factory workers, for example, increases the risk of tears or ruptures in the tendons; thirty percent of all people will have a tendon injury, with the risk being highest in women. What’s more, those who suffer from these injuries are more prone to further injuries at the site or never recover fully.
Tendons are bands of fibrous connective tissue that attach muscles to bones. They are soft tissues connected to stiff bones; this creates a complex interface with a very specific structure. Following injury, this structure is disrupted, and the connective tissue changes from a linear to a kinked formation. Excess scarring can also occur, changing the tendon’s mechanical properties and its ability to bear loads.
During the body’s natural healing processes, tendon and other cells are recruited to reconstruct the tendon’s original matrix of aligned connective tissue fibers. But this reconstruction can take weeks to months and the resultant tendon is often imperfect. This results in weakness, chronic pain and decreased quality of life.
Possible treatments for tendon injuries include tendon tissue grafts from patients or donors, but these pose risks such as infections, transplant rejection or necrosis. Synthetic transplants have been attempted, but mechanical, biocompatibility and biodegradation issues have hampered these efforts.
Another approach is to use mesenchymal stem cells (MSCs), specialized cells that play a pivotal role in tissue regeneration. At the wound site, they can differentiate into various cells types and produce signaling molecules which regulate immune response, cellular migration, and new blood vessel formation; this enables tissue regeneration.
However, treatment methods using systemic infusion, direct injection or genetic modification of MSCs present their own difficulties: infusion lacks targeting specificity to the injury site, direct injection requires prohibitively high cell numbers, and genetic modification is inefficient and produces cells that are difficult to isolate.

Adults who failed to pay down student debt, or took on new educational debt, between young adulthood and early mid-life face an elevated risk of cardiovascular illness, researchers report in the American Journal of Preventive Medicine, published by Elsevier. Adults who repaid their student debt had better or equivalent health than individuals who never faced student debt, suggesting that relieving the burden of student debt could improve population health.
“As the cost of college has increased, students and their families have taken on more debt to get to and stay in college. Consequently, student debt is a massive financial burden to so many in the United States, and yet we know little about the potential long-term health consequences of this debt. Previous research showed that, in the short term, student debt burdens were associated with self-reported health and mental health, so we were interested in understanding whether student debt was associated with cardiovascular illness among adults in early mid-life,” explained lead investigator Adam M. Lippert, PhD, Department of Sociology, University of Colorado Denver, Denver, CO, USA.
The study utilized data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a panel study of 20,745 adolescents in Grades 7 to 12 first interviewed during the 1994-1995 school year. Four subsequent waves of data were collected, including Wave 3, when the respondents were aged 18-26 and Wave 5, when respondents were aged 22-44. Wave 5 respondents were invited to in-home medical exams.
Researchers assessed biological measures of cardiovascular health of 4,193 qualifying respondents using the 30-year Framingham cardiovascular disease (CVD) risk score, which considers sex, age, blood pressure, antihypertensive treatment, smoking status, diabetes diagnosis, and body mass index to measure the likelihood of a cardiovascular illness over the next 30 years of life. They also looked at levels of C-reactive protein (CRP), a biomarker of chronic or systemic inflammation.
The investigators classified student debt according to the following categories: never had student debt; paid off debt between Waves 3 and 5; took on debt between waves; and consistently in debt. Models were adjusted for respondent household and family characteristics including education, income, and other demographics.
The researchers found that more than one third of respondents (37%) did not report student debt in either wave, while 12% had paid off their loans; 28% took on student debt; and 24% consistently had debt. Respondents who consistently had debt or took on debt had higher CVD risk scores than individuals who had never been in debt and those who paid off their debt. Interestingly, respondents who paid off debt had significantly lower CVD risk scores than those never in debt. They found clinically significant CRP value estimates for those who took on new debt or were consistently in debt between young adulthood and early mid-life, estimates that exceeded their counterparts who never had debt or paid it off. Race/ethnicity had no impact on the results.
Supplemental analyses suggested that, on balance, degree completion provides health benefits even to those with student debt, although these benefits were diminished relative to non-debtors. Dr. Lippert observed that these findings underscore the potential population health implications of transitioning to debt-financed education in the US. Though the empirical evidence is clear on the economic and health returns from a college degree, these advantages come at a cost for borrowers.
“Our study respondents came of age and went to college at a time when student debt was rapidly rising with an average debt of around $25,000 for four-year college graduates. It’s risen more since then, leaving young cohorts with more student debt than any before them,” Dr. Lippert said. “Unless something is done to reduce the costs of going to college and forgive outstanding debts, the health consequences of climbing student loan debt are likely to grow.”
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