The study, published this week in the journal Environmental Health Perspectives, also noted an association between preconception exposure to phthalates and changes in women’s reproductive hormones, as well as increased inflammation and oxidative stress.

“Phthalates are ubiquitous endocrine disruptors and we’re exposed to them every day,” says lead author Carrie Nobles, assistant professor of environmental health sciences in the School of Public Health and Health Sciences.

Phthalates are found in such common products as shampoo, makeup, vinyl flooring, toys and medical devices. People are exposed primarily by ingesting food and liquid that has come in contact with products containing the chemicals, according to a Centers for Disease Control and Prevention fact sheet.

Nobles and team analyzed data from a “unique cohort” of women in the preconception time-to-pregnancy study known as EAGeR (Effects of Aspirin in Gestation and Reproduction), which evaluated the effect of low-dose aspirin on live-birth rates. The study includes detailed information on 1,228 participants during six menstrual cycles when they are attempting to get pregnant. The women who became pregnant were followed through pregnancy.

“We were able to look at some environmental exposures like phthalates and how that relates to how long it takes to get pregnant. There was detailed data for each menstrual cycle, so we had a good handle on the date of ovulation and the timing of pregnancy when that happened,” Nobles says.

The body breaks down phthalates into metabolites that are excreted in urine and can be analyzed. The researchers measured 20 phthalate metabolites in urine samples taken when the participants enrolled in the study.

“We found there were three parent compounds that seem to be most strongly associated with taking longer to get pregnant, although we saw a general trend toward it taking longer to get pregnant across the phthalates we looked at,” Nobles says. “As exposure got higher, we saw more and more of an effect.”

The researchers also looked at a global marker of inflammation, C-reactive protein, and found the women who had higher levels of phthalates exposure also had higher levels of inflammation and oxidative stress, which can lead to organ and tissue damage and ultimately to disease.

In addition, women who showed higher levels of phthalates had lower estradiol and higher follicle-stimulating hormone across the menstrual cycle, which play an important role in ovulation and the early establishment of pregnancy.

“This profile — estradiol staying low and follicle-stimulating hormone staying high — is actually something that we see in women who have ovarian insufficiency, which can happen with age as well as due to some other factors,” Nobles says. “Ovulation just isn’t happening as well as it used to.”

While women can check consumer product labels and look for phthalate-free options, the ubiquitous nature of the chemicals makes it difficult for an individual to control their exposure.

In Europe, certain phthalates are banned or severely restricted in their use, but the U.S. has no formal prohibitions. Nobles says the research findings add to the evidence that phthalates exposures have a negative impact on women’s reproductive health and can be used to help inform policy making.

“Maybe we want to think differently about our regulatory system and how we identify important exposures that are having adverse effects on whether people can get pregnant and have a healthy pregnancy,” Nobles says.

Over the past few decades, hydrogels have received a lot of attention for treating skin wounds. When applied over a lesion, these special gels can promote healing by absorbing discharged fluids (exudates) and keeping the wound protected, well-hydrated, and oxygenated.

However, most developed hydrogels are given adhesive properties to skin tissue to follow skin movement. Since these hydrogels are sticky and adhere to the skin and wound site, they stretch and expand the wound itself once they swell up after absorbing exudates. This not only causes pain to the user but also puts them at a higher risk of bacterial infection due to the wound area expansion. Therefore, in order to create hydrogels that can effectively treat wounds without interfering with the wound healing process, it is necessary to experiment with the preparation of hydrogels based on new ideas while utilizing existing material properties.

Against this backdrop, a team of researchers from Tokyo University of Science (TUS), Japan, have now proposed an innovative and highly-value added medical material for treating skin wounds. As reported in their recent study published in the International Journal of Biological Macromolecules, they developed a novel, low-cost hydrogel using a component found in seaweed, achieving physical properties completely different from those of conventional hydrogels. The study, which was made available online on 8 November 2023, and will be published in Volume 254, Part 3 of the journal in January 2024, was led by Mr. Ryota Teshima, a Master’s student at TUS. Assistant Professor Shigehito Osawa, Ms. Miki Yoshikawa, Associate Professor Yayoi Kawano, Professor Hidenori Otsuka, and Professor Takehisa Hanawa, all from different faculties and departments at TUS, were also a part of this study.

The method of preparation of the proposed hydrogel is quite straightforward. It was made using alginate, calcium carbonate, and carbonated water. Alginate is a biocompatible substance that can be extracted from beach-cast seaweed. Most importantly, it does not adhere strongly to cells or skin tissues. Thanks to the special structure formed by alginate and calcium ions, in addition to the protective effect of the CO₂ in carbonated water against acidification, the resulting hydrogel not only exhibited ideal pH and moisture conditions for wound recovery but also demonstrated significantly lower adhesion and swelling, compared to other commercial hydrogel wound dressings.

The researchers tested the effectiveness of their new hydrogel using cell cultures and a mouse model, both of which yielded excellent results. “Through animal experiments, we demonstrated that our hydrogel has a high therapeutic effect and at the same time can suppress the temporary expansion of the wound area caused by conventional clinical preparations,” remarks Mr. Teshima. “This proves our initial hypothesis that gels with low skin adhesion and low-swelling properties are excellent as wound dressing materials, which is the complete opposite of conventional wisdom.”

Worth noting, alginate can be extracted from beach-stranded seaweed, a renewable resource that is often regarded as a coastal waste material. Since the proposed hydrogel is not only inexpensive but also biodegradable, this development marks an important step towards future progress on sustainable medicine. “Medical materials still lack a sustainability-oriented perspective, and we believe this research will serve as a benchmark for the design of future medical materials and lead to sustainable and low-cost wound care,” says Mr. Teshima. “Moreover, our findings can help clarify issues with hydrogel formulations currently in clinical use and provide new design guidelines for next-generation wound treatment gels.”

The team used CRISPR gene editing technologies to knock out the cytoglobin gene in zebrafish. The lack of cytoglobin caused the development of embryos with a mirrored heart, meaning the heart had a reversed left-right pattern. In humans, cytoglobin is involved in processes involving nitric oxide, a compound that helps regulate healthy blood flow to organs. Study co-senior author Mark T. Gladwin, MD, the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine, and Vice President for Medical Affairs, University of Maryland, Baltimore, has been researching the effects of nitric oxide on blood vessels for more than 20 years including in this recent study finding.

“Since its discovery two decades ago, cytoglobin has been found to be expressed in nearly all human tissues, but the mechanisms of how this protein functions were largely unknown,” said Dr. Gladwin. “We know that cytoglobin can play a role in modulating and maintaining nitric oxide levels, but our new finding indicates that it positively regulates NO production to ensure proper cilia function and its absence can lead to major laterality abnormalities of organs.”

To conduct the study, the research team knocked out the gene for cytoglobin in zebrafish and were amazed to see that it led to dramatic defects in the structure and location of organs in developing embryos. The heart, for example, was located on the right side of the fish instead of the left with a looping to the left instead of the right.

“We found that cytoglobin plays a vital role in the structure and function of tiny hair-like structures called cilia, which determine the asymmetry and proper development of organs,” said study senior author Paola Corti, PhD, Assistant Professor of Biochemistry and Molecular Biology at UMSOM.

This is the first time cytoglobin — or any of the globin proteins like hemoglobin — has been found to be involved in fetal development and that a paucity could be linked to birth defects. It’s also the first time that cytoglobin has been linked to cilia function. Such a finding could open the door for the development of therapeutics for rare birth defects that affect the movement of cilia.

About 1 in every 10,000 to 30,000 people are born with Primary Ciliary Dykinesia (PCD), a rare disease that affects the cilia and can cause breathing issues from thickened mucus clogging airways. “Kartagener’s syndrome is a form of PCD and is known to cause the type of heart defects seen in the zebrafish where the heart is abnormally positioned to the right and rotated,” said Dr. Corti. “There is no cure for this condition, just surgery to fix any heart defects and treatments to manage symptoms.”

While certain genes have been identified that are known to cause about 70 percent of PCD cases, cytoglobin could play a key role in the 30 percent of cases with no known genetic cause.

“We found the phenotype and connected the dots to cilia. In the presence of cytoglobin, we could track the function of the protein and how if led to proper cilia function and organ development. In the absence, we saw these defects,” said Elizabeth Rochon, PhD, first author of the study and Assistant Professor of Medicine at UMSOM.

Funding for the study was from the National Institutes of Health, the American Heart Association, and the Institute for Transfusion Medicine and the Hemophilia Center. UMSOM faculty co-authors include Anthony W. DeMartino, PhD, Assistant Professor of Medicine, and Qinzi Xu, MD, Assistant Professor of Medicine.

Other co-authors included faculty at the University of Pittsburgh School of Medicine and the University of Copenhagen in Denmark.

The new study comparing the viruses that cause COVID-19 and the flu also revealed that in the 18 months after infection, patients hospitalized for either COVID-19 or seasonal influenza faced an increased risk of death, hospital readmission, and health problems in many organ systems. Further, the time of highest risk was 30 days or later after initial infection.

“The study illustrates the high toll of death and loss of health following hospitalization with either COVID-19 or seasonal influenza,” said senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University. “It’s critical to note that the health risks were higher after the first 30 days of infection. Many people think they’re over COVID-19 or the flu after being discharged from the hospital. That may be true for some people. But our research shows that both viruses can cause long-haul illness.”

The findings are published Dec. 14 in The Lancet Infectious Diseases.

The statistical analysis spanned up to 18 months post-infection and included a comparative evaluation of risks of death, hospital admissions and 94 adverse health outcomes involving the body’s major organ systems.

“A review of past studies on COVID-19 versus the flu focused on a short-term and narrow set of health outcomes,” said Al-Aly, who treats patients within the VA St. Louis Health Care System and is an assistant professor of medicine at Washington University. “Our novel approach compared the long-term health effects of a vast array of conditions. Five years ago, it wouldn’t have occurred to me to examine the possibility of a ‘long flu.’ A major lesson we learned from SARS-CoV-2 is that an infection that initially was thought to only cause brief illness also can lead to chronic disease. This revelation motivated us to look at long-term outcomes of COVID-19 versus flu.

“We wanted to know whether and to what degree people with flu also experience long-term health effects,” Al-Aly said. “The big answer is that both COVID-19 and the flu led to long-term health problems, and the big aha moment was the realization that the magnitude of long-term health loss eclipsed the problems that these patients endured in the early phase of the infection. Long COVID is much more of a health problem than COVID, and long flu is much more of a health problem than the flu.”

However, the overall risk and occurrence of death, hospital admissions, and loss of health in many organ systems are substantially higher among COVID-19 patients than among those who have had seasonal influenza, Al-Aly said. “The one notable exception is that the flu poses higher risks to the pulmonary system than COVID-19,” he said. “This tells us the flu is truly more of a respiratory virus, like we’ve all thought for the past 100 years. By comparison, COVID-19 is more aggressive and indiscriminate in that it can attack the pulmonary system, but it can also strike any organ system and is more likely to cause fatal or severe conditions involving the heart, brain, kidneys and other organs.”

The researchers analyzed de-identified medical records in a database maintained by the U.S. Department of Veterans Affairs, the nation’s largest integrated health-care delivery system. They evaluated information involving 81,280 patients hospitalized for COVID-19 at some point from March 1, 2020, through June 30, 2022, as well as 10,985 patients hospitalized for seasonal influenza at some point from Oct. 1, 2015, through Feb. 28, 2019.

Patients represented multiple ages, races and sexes.

Regarding both viruses, patient vaccination status did not affect results. Those in the COVID-19 cohort were hospitalized during the pre-delta, delta and omicron eras.

During the overall 18-month study period, patients who had COVID-19 faced a 50% higher risk of death than those with seasonal influenza. This corresponded to about eight more deaths per 100 persons in the COVID-19 group than among those with the flu.

Although COVID-19 showed a greater risk of health loss than seasonal influenza, infection with either virus carried significant risk of disability and disease. The researchers found COVID-19 exhibited increased risk of 68% of health conditions examined across all organ systems (64 of the 94 adverse health outcomes studied), while the flu was associated with elevated risk of 6% of health conditions (six of the 94) — mostly in the respiratory system.

Also, over 18 months, COVID-19 patients experienced an increased risk of hospital readmission as well as admission to an intensive care unit (ICU). For every 100 persons in each group, there were 20 more hospital admissions and nine more ICU admissions in COVID-19 than flu.

“Our findings highlight the continued need to reduce the risk of hospitalization for these two viruses as a way to alleviate the overall burden of health loss in populations,” Al-Aly said. “For both COVID-19 and seasonal influenza, vaccinations can help prevent severe disease and reduce the risk of hospitalizations and death. Optimizing vaccination uptake must remain a priority for governments and health systems everywhere. This is especially important for vulnerable populations such as the elderly and people who are immunocompromised.”

In both COVID-19 and the flu, more than half of death and disability occurred in the months after infection as opposed to the first 30 days, the latter of which is known as the acute phase.

“The idea that COVID-19 or flu are just acute illnesses overlooks their larger long-term effects on human health,” Al-Aly said. “Before the pandemic, we tended to belittle most viral infections by regarding them as somewhat inconsequential: ‘You’ll get sick and get over it in a few days.’ But we’re discovering that is not everyone’s experience. Some people are ending up with serious long-term health issues. We need to wake up to this reality and stop trivializing viral infections and understand that they are major drivers of chronic diseases.”

“Thanks to this elaborate structure in their nasal cavities, Arctic seals lose less heat through nasal heat exchange than subtropical seals when both are exposed to the same conditions,” says corresponding author and physical chemist Signe Kjelstrup of the Norwegian University of Science and Technology. “This provides an evolutionary advantage, especially in the Arctic where heat loss is energy dissipation, which must be replenished by food.”

“What’s so amazing is that these Arctic seals retain 94% of the water when they breathe in and out,” says Kjelstrup. “This means that most of the water added to the air during inhalation is then recovered during exhalation.”

In cold, dry environments, animals lose heat and moisture just by breathing. Most mammals and birds have complex bones called maxilloturbinates inside their nasal cavities that help to minimize this risk. These porous, bony shelves are covered with a richly vascularized layer of mucosal tissues that warm and humidify inhaled air, which is important for lung function, and reduce the amount of heat and moisture lost during exhalation.

The structure of these bones varies between species, however. Kjelstrup’s team previously showed that reindeer noses enable efficient heat exchange in cold conditions, but because reindeer don’t live in diverse environments, they turned to seals to test whether there’s anything special about the noses of Arctic animals.

“You can’t find reindeer in the middle of the Mediterranean, but seals live in many different environments, so they allowed us to test this question,” says Kjelstrup. “And we knew from a previous study that Arctic seal noses are sponge-like and very dense, whereas the Mediterranean seal nose has a more open structure.”

The researchers used computer tomography to make 3D models of the nasal cavities/maxilloturbinates of an Arctic species of seal, the bearded seal (Erignathus barbatus), and a subtropical species, the Mediterranean monk seal (Monachus monachus). Then, they used energy dissipation models to compare the seals’ ability to warm and moisten air during inhalation and to reduce heat and moisture loss during exhalation. The team tested both seals under Arctic conditions (−30°C), and at 10°C, which would represent a cold day for a Mediterranean monk seal. They also tweaked different parameters within the model to identify geometrical features of the nasal cavity that are important for its function.

The model indicated that Arctic seals are much more efficient than subtropical seals at retaining heat and water exchange in both Arctic and Mediterranean ambient temperatures. At −30°C, the subterranean seals lost 1.45 times as much heat and 3.5 times as much water per breath cycle as the Arctic seals, and at 10°C, the subterranean seals lost 1.5 times as much heat and 1.7 times as much water.

This advantage was due to the Arctic seal’s more complex, dense nasal cavity. Specifically, the researchers showed that the increased perimeter of the Arctic seal’s maxilloturbinates is key to limiting energy dissipation at low ambient temperatures.

The study investigated moisture and heat loss per breath cycle (i.e., for one inhalation and exhalation), but the role of breathing rate remains unclear. This is especially complicated for seals, who pause their breathing for minutes at a time when they dive.

In the future, the researchers hope to study the nasal structures of other species to see if different structures provide evolutionary advantages in other environments. “The camel, for instance, doesn’t need to save much on heat, but it does need to save on water, so one may speculate that it could tell us something about relative importance of the two,” says Kjelstrup.

Ultimately, the researchers plan to use this information to engineer more efficient heat exchangers and ventilation systems. “If nature manages to create such great heat exchangers, I think we should copy that in engineering to create more efficient processes, for instance, in air conditioners,” says Kjelstrup.

This research was supported by the Research Council of Norway and the Tromsø Research Foundation.

Following a recent proof-of-principle demonstration, researchers are adding a new combination of compounds to the quantum materials roster.

In a study reported in ACS Photonics, researchers combined two nanosized structures — one made of diamond and one of lithium niobate — onto a single chip. They then sent light from the diamond to the lithium niobate and measured the fraction of light that successfully made it across.

The greater that fraction, the more efficient the coupling of the materials, and the more promising the pairing as a component in quantum devices.

The result: An extraordinary 92% of the light made the jump from diamond to lithium niobate.

The research was supported in part by Q-NEXT, a U.S. Department of Energy (DOE) National Quantum Information Science Research Center led by DOE’s Argonne National Laboratory. Stanford University’s Amir Safavi-Naeini and Jelena Vuckovic led the study.

“It was an exciting result to get 92% efficiency from this device,” said Hope Lee, paper co-author and a Ph.D. student at Stanford University and researcher who worked with Q-NEXT Director David Awschalom while an undergraduate at the University of Chicago. “It showed the advantages of the platform.”

A bit about qubits

Quantum technologies harness special features of matter at the molecular scale to process information. Quantum computers, networks and sensors are expected to have an enormous impact on our lives in areas such as medicine, communication and logistics.

Quantum information is delivered in packets called qubits, which can take many forms. In the research team’s new platform, qubits transmit information as particles of light.

Reliable qubits are critical for technologies such as quantum communication networks. As in traditional networks, information in quantum networks travels from one node to another. Stationary qubits store information within a node; flying qubits carry information between nodes.

The research team’s new chip would form the basis of a stationary qubit. The more robust the stationary qubit, the more reliable the quantum network, and the greater the distance that networks can cover. A quantum network spanning a continent is well within reach.

A material advantage

Diamond has long been touted as a great home for qubits. For one, diamond’s molecular structure can be easily manipulated to host stationary qubits. For another, a diamond-hosted qubit can maintain information for a relatively long time, meaning more time for performing computations. Also, computations performed using diamond-hosted qubits exhibit high accuracy.

Diamond’s partner in the group’s study, lithium niobate, is another star performer when it comes to processing quantum information. Its special properties give scientists versatility by allowing them to change the frequency of the light passing through it. For example, researchers can apply an electric field or a mechanical strain to the lithium niobate to adjust how it channels light. It’s also possible to flip the orientation of its crystal structure. Doing this at regular intervals is another way to shape light’s passage through the material.

“You can use these properties of the lithium niobate to convert and change the light coming from the diamond, modulating it in ways that are useful for different experiments,” said Jason Herrmann, paper co-author and a Ph.D. student at Stanford. “For instance, you can basically convert the light into a frequency used by existing communications infrastructure. So those properties of lithium niobate are really beneficial.”

A powerful pairing

Traditionally, light from diamond-hosted qubits is channeled into either a fiber-optic cable or free space. In both cases, the experimental setup is unwieldy. Fiber-optic cables are long, dangly and floppy. And transmitting qubits into free space requires bulky equipment.

All that equipment goes away when light from the diamond’s qubits is instead channeled into lithium niobate. Nearly every component can be placed on one tiny chip.

“There’s an advantage to having as many of your devices and your functionalities as possible on a single chip,” Lee said. “It’s more stable. And it really allows you to miniaturize your setups.”

Not only that, but because the two devices are connected by a whisper-thin filament — 1/100 of the width of a human hair — the quantum light is squeezed into the narrow passage that leads to lithium niobate, increasing the light’s interaction with the material and making it easier to manipulate light’s properties.

“When all the different light particles are interacting together in such a small volume, you get a much higher efficiency in the conversion process,” Herrmann said. “Being able to do this in the integrated platform will hopefully give rise to much higher efficiencies compared to the setup with fibers or free space.”

A challenging assembly

One of the challenges of developing the platform was manipulating the diamond — a mere 300 nanometers wide — to align with the lithium niobate.

“We had to poke at the diamond with tiny little needles to shift it around until it visibly looked like it was in the correct spot on this plate,” Lee said. “It’s almost like you’re poking at it with little chopsticks.”

Measuring the transferred light was another painstaking process.

“We have to really make sure we’re accounting for all the places where light is transmitted or lost to be able to say, ‘This is how much is going from diamond to lithium niobate,'” Herrmann said. “That calibration measurement took a lot of back and forth to make sure we were doing it correctly.”

The team is planning further experiments that leverage the quantum-information advantages offered by diamond and lithium niobate, both separately and together. Their latest success is only one milestone in what they hope will be a diverse menu of devices based on the two materials.

“By putting these two material platforms together and channeling light from one to the other, we show that, instead of working with just one material, you can really have the best of both worlds,” Lee said.

This work was supported by DOE’s Office of Science National Quantum Information Science Research Centers as part of the Q-NEXT center. It was also supported by the U.S. National Science Foundation and the Swiss National Science Foundation.