Nanoparticles: Risk for babies in the womb

Human life begins with a single egg cell that grows into a human being with trillions of cells. To ensure that the highly complex development of tissues and organs is as protected as possible, the placental barrier keeps pathogens and foreign substances out. Tina Bürki and her team from Empa’s Particles-Biology Interactions laboratory in St. Gallen are investigating how this protective mechanism copes with nanoparticles.
Nanoparticles are contained in a large number of products, but they are also produced during wear and tear as well as through combustion processes (see box). “We absorb these substances from the environment via our food, cosmetics or the air we breathe,” explains Bürki. Some of these nanoparticles are suspected of harming babies in the womb. Low birth weight, autism and respiratory diseases are among the possible consequences for the child.
Mysterious remote effect
It is still unclear how the nanoparticles affect the unborn child. “We already know that the placental barrier retains many nanoparticles or at least delays their transport to the embryo,” says Bürki. However, damage to the fetal tissue occurs, even if no particles have been detected in the fetus. The Empa team is now getting to the bottom of this long-range effect of nanoparticles. Together with clinical partners from the Cantonal Hospital of St. Gallen and research partners from the University of Geneva, the Amsterdam University Medical Center and the Leibniz Institute for Environmental Medical Research in Düsseldorf, the team is investigating the consequences of common nanoparticles such as titanium dioxide or diesel soot on the function of the placenta and their indirect damage to embryonic development.
For this purpose, the team used fully functional human placentas that were made available after planned caesarean sections. “Human placental tissue is the only way to obtain meaningful results on the transport and effect of nanoparticles,” says the Empa researcher. “The structure, metabolism and interaction of maternal and fetal tissue are unique and species-specific.”
The experiments showed that nanoparticles in placental tissue disrupt the production of a large number of messenger substances. And it is these messengers that can trigger serious changes in embryonic development, such as disturbed blood vessel formation.
These effects can be visualized in laboratory models using chicken eggs. The blood vessels in the egg actually grow at an enormous speed and density to enable embryonic development. A dense network of fine blood vessels covers the inside of the eggshell. The situation is strikingly different in eggs treated with the altered messenger substances from the nanoparticle-treated placenta: In the experiments, the blood vessel system was not as dense but rather coarse-meshed. “Nanoparticles apparently have an indirect effect on the child in the womb by inhibiting the formation of blood vessels via messenger substances,” says Tina Bürki.

Health consequences
The researchers are currently investigating the entirety of the messenger substances released by a nanoparticle-treated placenta, the so-called secretome. Uncontaminated, the interplay of hormones, inflammatory mediators and signaling substances for the formation of organ systems resembles a perfectly tuned orchestra. It is already clear that the communication between the placenta and the unborn child is disrupted by the presence of nanoparticles and damages the formation of blood vessels. However, initial results show that the development of the nervous system does not appear to be affected. Future analyses will show what other disorders the nanoparticles can trigger indirectly. “As the effects can have an impact on the health of the pregnant woman and the development of her child, these findings should be taken into account in the risk assessment of nanomaterials,” says the researcher.
The clinical partner, the Cantonal Hospital of St. Gallen, is also interested. As Thomas Rduch from the Women’s Clinic and also a Clinical Research Fellow at Empa puts it: “A healthy placenta is of utmost importance for the development of the child. Correct risk assessments of environmental pollution are therefore crucial for pregnant women.”
The placenta
The placenta is an organ that forms exclusively during pregnancy. It supplies the child in the womb with nutrients and also serves as a filter for environmental influences. This so-called placental barrier offers the unborn child a certain degree of protection against pathogens or harmful substances. However, some substances, such as environmental estrogens can pass through the placental barrier and are suspected of being associated with various diseases.
Nanoparticles
Nanoparticles are only a few millionths of a millimeter in size. They include titanium dioxide, for example, which can be found in many foods, cosmetics and medicines. Silicon dioxide is found in paints and printing paper, for example, and is also used as a food additive. Other nanoparticles come from environmental pollution processes such as plastic abrasion (nanoplastics) or industrial soot. They can enter the human body via the respiratory tract, the digestive tract or the skin.

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Women with excess weight as a teen or young adult may have higher stroke risk by age 55

In an analysis of more than 50 years of health data, women who had overweight or obesity at age 14 or 31 were more likely to have an ischemic (clot-caused) stroke before age 55, according to research published today in Stroke, the peer-reviewed scientific journal of the American Stroke Association, a division of the American Heart Association.
According to the American Heart Association, an ischemic stroke occurs when a vessel supplying blood to the brain is obstructed. Ischemic stroke is the most common type of stroke and accounts for about 87% of all strokes.
The study conducted in Finland suggests that women with overweight at age 14 were associated with later clot caused stroke risk despite having lost weight by age 31. Also, women with overweight at age 31 were associated with later clot caused stroke risk despite having been normal weight at age 14. An increased risk of clot caused stroke was not found in men who were overweight at ages 14 or 31. However, men with obesity at age 31 had a higher risk of bleeding stroke compared to women with obesity at age 31.
“Our findings suggest that being overweight may have long-term health effects even if the excess weight is temporary,” said lead study author Ursula Mikkola, B.M., an investigator in the Research Unit of Population Health at the University of Oulu in Finland. “Health care professionals should pay attention to overweight and obesity in young people and work with them to develop healthier eating patterns and physical activity. However, conversations with teens and young adults about weight should be approached in a non-judgmental and non-stigmatizing manner.”
To analyze the association between weight at different ages and the risk of stroke before age 55, the researchers reviewed long-term data from participants in the Northern Finland Birth Cohort 1966. The Northern Finland study group was initiated to help understand factors related to preterm birth and infant deaths. In 1966, more than 12,000 pregnant women were enrolled from two northern provinces in Finland. More than 10,000 offspring, now in their 50s, have been followed ever since, with their health information used in multiple research studies.
For this analysis, researchers used the body mass index (BMI), a ratio of weight to height, to explore whether those who were overweight or obese at age 14 or age 31 had a different risk of early stroke compared to peers who were not overweight or obese at age 14 or 31. About 1 in 20 participants experienced a clot-caused stroke or transient ischemic attack (TIA, or mini-stroke) during the average follow-up period of almost 39 years after the age 14 evaluation and almost 23 years after the age 31 evaluation. The current study’s analysis ended in 2020.
Assessing the impact of periods of excess weight on stroke risk, the researchers found: Women affected by obesity at age 14 were 87% more likely to have an early clot-caused stroke or mini-stroke, while those with obesity at age 31 were 167% more likely to have a stroke compared to those at appropriate weight. Similar associations were not found among men. Women with obesity at age 31 had almost 3 ½ times increased risk of bleeding stroke, and men with obesity at age 31 had more than 5 ½ times increased risk of bleeding stroke. BMI measurements earlier in childhood or later in adulthood did not appear to affect the results.It is important to note that weight is not the only health factor that impacts stroke risk. Many other factors affect stroke risk and should be considered in addition to weight. “By living a healthy lifestyle (eating better, not smoking, healthy sleep, managing blood pressure, cholesterol and blood glucose levels, avoiding excess alcohol use and being physically active), you can lower your risk of stroke even if you were overweight when you were younger,” Mikkola added.

Researchers do not know why the association of increased risk for clot-caused stroke was not found in men. Researchers are currently investigating the potential causes as well as other risk factors in more detail.
In an accompanying editorial Larry Goldstein, M.D., FAHA, notes, “This study provides additional evidence of an association between overweight/obesity and stroke in young adults. However, while it is tempting to assume that reductions in overweight/obesity in younger populations would translate to lower stroke rates in young adults, this remains to be proven.” Goldstein is an American Heart Association Stroke Council member and chair of the department of neurology and co-director of the Kentucky Neuroscience Institute, University of Kentucky HealthCare in Lexington, Kentucky.
Study details, background and design: The analysis was conducted from 1980 to 2020. Participants in the analysis included 10,491 people in their 50s (49% women). BMI was measured at age 14, age 31, or both. Sex- and age-based norms were used to classify participants as overweight or obese based on their BMI. Ischemic strokes and transient ischemic attacks between age 14 and age 54 were identified using national hospital and death registers. The association between BMI or changes in BMI and the occurrence of stroke were identified after adjusting for participants’ sex, smoking status, education levels (for parents when participants were age 14 and for participants when they were age 31). BMI at the other time point (such as BMI at age 31 vs. BMI at age 14 ) and age at first menstrual period for women was also considered. The follow-up data continued until participants’ first stroke, death, moving abroad or the end of year 2020, whichever came first.Limitations of the study include that it is an analysis of health data (an observational study) and, therefore, it cannot prove a cause-and-effect relationship between weight and early stroke risk. Participants were all born in Finland, so the results may not be generalizable to people in other countries.
“Stroke at a young age is rare, so the difference of just a few strokes could have an outsized impact on the risk estimates,” Mikkola said. “Also, BMI relies solely on a person’s height and weight, therefore, a high BMI may be a misleading way to define obesity, especially in muscular people who may carry little fat even while weighing more.”

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New glioblastoma treatment reaches human brain tumor and helps immune cells recognize cancer cells

In a major advance for the treatment of the deadly brain cancer glioblastoma, Northwestern Medicine scientists used ultrasound technology to penetrate the blood-brain barrier and provide a small dose of a chemotherapy and immunotherapy drug cocktail. The study found that this treatment boosted the immune system’s recognition of the cancer cells and could lead to a new treatment approach.
The scientists made several breakthroughs reported in a new study to be published in Nature Communications this Thursday, June 6.
Scientists showed for the first time that a skull-implantable ultrasound device can enhance the penetration of the chemotherapy drug doxorubicin and immune checkpoint blockade antibodies — a novel immunotherapy treatment combination — into the human brain. The device produces microbubbles that temporarily open the blood-brain barrier, allowing the immunotherapy to enter the brain.
The scientists also showed for the first time that a small dose of doxorubicin (smaller than the dose used for traditional chemotherapy regimens) delivered with the immune checkpoint antibodies can boost the recognition of malignant glioblastoma cells by the immune system and reinvigorate the lymphocytes (immune cells) that are in charge of attacking the cancer cells.
An immune checkpoint blockade antibody blocks the deactivation of the immune system by the cancer cells. The immune system has built-in brakes — called immune checkpoints — so it doesn’t overdo it and injure the body when attacking cancer and infections. Glioblastoma evolves to activate the brakes, and therefore, the immune system (i.e., lymphocytes) won’t attack it.
In addition to the tumor cells, glioblastoma contains other cell populations called macrophages and microglia. These are the most abundant components of the tumor microenvironment and the cells that glioblastoma modulates to inhibit lymphocytes. The study showed that the chemo and antibody cocktail altered these cells, enabling the lymphocytes to recognize and kill the cancer cells.
“This is the first report in humans where an ultrasound device has been used to deliver drugs and antibodies to glioblastoma to change the immune system, so it can recognize and attack the brain cancer,” said co-corresponding author Dr. Adam Sonabend, associate professor of neurological surgery at Northwestern University Feinberg School of Medicine and a Northwestern Medicine neurosurgeon. “This could be a major advance for the treatment of glioblastoma, which has been a frustratingly difficult cancer to treat, in part due to poor penetration of circulating drugs and antibodies into the brain.”
The study was conducted in four patients who had advanced progression of their tumors. They had already been treated with conventional chemotherapy for their tumors as well as an experimental treatment in a clinical trial, but both times, the tumors returned.

“This is a great example of translational bench-to-bedside-back-to-bench research, which sets an exceptional scenario to learn about the ability of the immune system to kill brain tumors in real-time upon treatment,” said co-corresponding author Catalina Lee-Chang, assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine. “Given the lack of effective immune response against these deadly tumors, these findings encourage us to envision a potential new treatment approach.”
Clinical trial launched with new treatment
These new findings are the basis for a novel clinical trial that was just launched at Northwestern using the ultrasound to deliver the immunotherapy for glioblastoma. The trial will initially enroll 10 participants to determine the safety of the treatment, followed by 15 additional to measure whether the treatment can prolong survival.
Previous large clinical trials have failed to show that this type of immunotherapy can prolong survival in glioblastoma patients. Sonabend, however, believes that by enhancing the delivery of these antibodies and drugs into the brain and relying on biomarkers that indicate which tumors are most susceptible to immunotherapy, this treatment might be shown to be effective for some glioblastoma patients.
“Here we show in a small cohort of patients that when you use this technology, you can enhance the delivery of the chemotherapy and the antibodies, and change the tumor’s microenvironment, so the immune system can recognize the tumor,” Sonabend said.
Sonabend and Lee-Chang are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Malnati Brain Tumor Institute. Sonaband also is director of translational neuro-oncology at Feinberg.

The title of the article is “Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas.”
Other Northwestern authors include first author Vi?ctor A. Arrieta, Andrew Gould, Kwang-Soo Kim, Karl J. Habashy, Crismita Dmello, Gustavo I. Va?zquez-Cervantes, Irina Palaci?n-Aliana, Graysen McManus, Christina Amidei, Cristal G. Gomez, Silpol Dhiantravan, Li Chen, Daniel Y. Zhang, Ruth Saganty, Meghan E. Cholak, Surya Pandey, Matthew McCord, Kathleen McCortney, Brandyn Castro, Rachel Ward, Bin Zhang, Jason M. Miska, Maciej S. Lesniak, Craig M. Horbinski, Rimas V. Lukas and Roger Stupp.
The research was supported in part by the National Cancer Institute grants 1R01NS110703-01A1, 1U19CA264338-01 and 1R01CA245969-01A1 of the National Institutes of Health, grant P50CA221747 SPORE for Translational Approaches to Brain Cancer and the Moceri Family Foundation and the Panattoni family.

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Searchable database for Alzheimer’s research

A searchable database is now ready to help study Alzheimer’s disease.
Neuroscience and biomedical informatics researchers at The Ohio State University Wexner Medical Center and College of Medicine created the comprehensive, user-friendly repository.
The free database — known as ssREAD — is outlined in a manuscript published online in Nature Communications.
Alzheimer’s disease is the most common cause of dementia, accounting for up to 80% of cases. An estimated 6.7 million Americans who are age 65 and older are living with Alzheimer’s dementia today, according to the Alzheimer’s Association’s 2023 Alzheimer’s disease facts and figures report.
This database will help study the pathology of Alzheimer’s disease. Pathology examines the cause, development, structural/functional changes and natural history associated with diseases.
Molecular signatures underlying Alzheimer’s disease pathology have been increasingly explored through single-cell and single-nucleus RNA-sequencing (scRNA-seq & snRNA-seq) and spatial transcriptomics.
“These technologies have cast fresh light on the exploration of Alzheimer’s disease pathogenesis and sex difference at the cellular and molecular levels. Our ssREAD repository offers a broader spectrum of Alzheimer’s disease-related datasets, with an optimized analytical pipeline and improved usability,” said study co-corresponding author Hongjun “Harry” Fu, PhD, assistant professor of neuroscience at Ohio State.

Datasets
The database encompasses 277 integrated datasets from 67 Alzheimer’s disease-related scRNA-seq & snRNA-seq studies, totaling 7,332,202 cells. The repository also includes 381 spatial transcriptomics samples from 85 human and mouse studies. Detailed annotations including cell types and spatial layers Differential gene expressions and functional enrichment analysis Spatially variable genes and deconvolution with single-cell datasetsInteractive visualizations
User-friendly web server to provide comprehensive analysis interpretations and filters support multiple selections Scatter plots for clusters, cell types, and spatial layers Feature plots and violin plots for gene expression profile Real-time gene set enrichment analysis”We are closing the gap for researchers by creating this specialized database. Integrating these diverse datasets and conditions will be invaluable for researchers studying the complex landscape of Alzheimer’s disease,” said Qin Ma, PhD, professor in Ohio State’s department of biomedical informatics.

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Using oceanography to understand fronts and cyclones on Jupiter

New research led by Lia Siegelman, a physical oceanographer at UC San Diego’s Scripps Institution of Oceanography, shows that the roiling storms at the planet Jupiter’s polar regions are powered by processes known to physicists studying Earth’s oceans and atmosphere. The geophysical commonalities spanning the 452 million miles between the two planets could even help facilitate an improved understanding of those processes on Earth.
Siegelman first made the connection between our planet and the gas giant in 2018 when she noticed a striking similarity between images of Jupiter’s huge cyclones and the ocean turbulence she was studying. To a physicist, air and water are both considered fluids so applying ocean physics to Jupiter isn’t as far-fetched as it sounds, said Siegelman. “Jupiter is basically an ocean of gas.”
This initial observation led Siegelman to co-author a 2022 study published in Nature Physics that analyzed high-resolution infrared images of Jupiter’s cyclones taken by NASA’s Juno spacecraft. The analysis revealed that a type of convection similar to what is seen on Earth helps maintain Jupiter’s storms, which can be thousands of miles wide and last for years.
The 2022 study focused directly on Jupiter’s cyclones, but Siegelman also saw wispy tendrils, known to researchers as filaments, in the spaces between the gassy vortices. These filaments also had earthly analogs, and Siegelman used Juno’s detailed imagery to study whether this similarity to our planet’s oceanic and atmospheric processes was merely skin deep.
Published on June 6 in Nature Physics (LINK TK) and funded by Scripps and the National Science Foundation, Siegelman’s follow-up study finds additional similarities between the processes fueling Jupiter’s cyclones and those acting on Earth. The study shows that the filaments between Jupiter’s cyclones act in concert with convection to promote and sustain the planet’s giant storms. Specifically, Jupiter’s filaments act in ways that resemble what oceanographers and meteorologists call fronts on Earth.
Fronts are often discussed in weather forecasts — cold fronts or storm fronts, for example — but they apply to both gases and liquids. A front is the boundary between gas or liquid masses with different densities due to differences in properties like temperature. In the ocean, fronts can also be due to differences in salinity, which influences the density of seawater along with temperature. A key feature of fronts is that their leading edges feature strong vertical velocities that can create winds or currents.
To try to understand the role of the filaments she could clearly see in between the cyclones on Jupiter in Juno’s images, Siegelman looked at a series of infrared images from Juno. The batch of images were of Jupiter’s north polar region and were taken in 30-second increments.

The fact that the images were in infrared allowed Siegelman and her co-author Patrice Klein of NASA’s Jet Propulsion Laboratory, California Institute of Technology, and the Ecole Normale Superieure to calculate temperature — bright areas were warmer and dark areas were cooler. On Jupiter, the hotter parts of the atmosphere correspond to thin clouds and the colder parts represent thick cloud cover, blocking more of the heat emanating from Jupiter’s super-heated core. The researchers then tracked the movement of clouds and filaments across the 30 second intervals separating the photographs to calculate horizontal wind speeds.
These two pieces of information allowed Siegelman and Klein to apply methods from ocean and atmospheric science to Jupiter, allowing them to calculate the vertical wind speeds that would correspond to the temperatures and horizontal wind speeds the researchers derived from the images. Once the team calculated the vertical wind speeds, they were able to see that Jupiter’s filaments were indeed behaving like fronts on Earth.
Those vertical wind speeds at the edges of fronts on Jupiter also meant that the fronts were involved in transporting energy in the form of heat from the planet’s hot interior to its upper atmosphere — fueling the giant cyclones. Though convection is the main driver, the fronts account for a quarter of the total kinetic energy powering Jupiter’s cyclones and forty percent of the vertical heat transport.
“These cyclones on Jupiter’s poles have persisted since they were first observed in 2016,” said Siegelman. “These filaments in between the large vortices are relatively small but they are an important mechanism for sustaining the cyclones. It’s fascinating that fronts and convection are present and influential on Earth and Jupiter — it suggests that these processes may also be present on other turbulent fluid bodies in the universe.”
Siegelman also said that Jupiter’s massive scale and Juno’s high-resolution imagery can allow for a clearer visualization of the ways in which smaller-scale phenomena like fronts connect to larger ones like cyclones and the atmosphere at large — connections that are often hard to observe on Earth where they are much smaller and more ephemeral. However, she added, a long-awaited new satellite known to researchers as SWOT, is poised to make these kinds of ocean phenomena vastly easier to observe.
“There is some cosmic beauty in finding out that these physical mechanisms on Earth exist on other far-away planets,” said Siegelman.

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Lifesaving childbirth blood loss intervention is highly cost-effective

A lifesaving package including early detection and bundled treatment for women who have heavy bleeding during childbirth has been found to incur minimal additional cost according to new analysis from 78 hospitals around the world.
In a paper published in Nature Medicine today, a team of researchers working on the E-MOTIVE trial conducted an economic analysis to establish whether a package of interventions to objectively identify and treat post-partum haemorrhage (PPH) was cost effective.
Over 200,000 women from hospitals across four countries in Africa were included in the economic analysis of E-MOTIVE, with hospitals being randomly assigned to either the intervention or usual care groups. The intervention resulted in more than 1000 fewer PPH cases compared to the usual care group. The additional cost for E-MOTIVE was estimated to be, on average, an extra $0.30 per patient after adjustments for clinical factors including the proportion of patients with a clinical primary outcome event at each hospital, as well as for cluster and time-period considerations. .
The economic analysis explored a range of costs for a key component of the E-MOTIVE package which is a calibrated blood collection drape, used for all women in the intervention group used to objectively measure blood loss. The analysis found that when the cost of the drape is around 1 USD, the average cost per patient could be comparable to usual care.
Tracy Roberts, Professor of Health Economics at the University of Birmingham and corresponding author of the study said:
“E-MOTIVE is clearly a cost-effective intervention for what is a lifesaving treatment for thousands of women around the world who may experience severe bleeding in childbirth. Our analysis of the E-MOTIVE trial shows that the costs incurred in delivering the package of treatments and the drape are on average minimal and represent really good value for money.”
“The drape forms a key part of the E-MOTIVE package, and should E-MOTIVE be widely adopted and the cost of drapes reduced to below $1, the economic benefits could be even more apparent. The cost of delivering the E-MOTIVE intervention could then be, on average, equivalent to usual care, which would represent a significant health benefit for women around the world.”
60% reduction in heavy bleeding

E-MOTIVE being found cost-effective comes after the publication of a landmark study published that found a 60% reduction in heavy bleeding for women experiencing PPH.
Postpartum haemorrhage (PPH) — defined as the loss of more than 500 mL of blood within 24 hours after birth — is the leading cause of maternal mortality worldwide. It affects an estimated 14 million women each year and results in around 70,000 deaths — mostly in low and middle-income countries — equivalent to 1 death every 6 minutes.
The study found that objectively measuring blood loss using a simple, low-cost collection device called a ‘drape’ and bundling together WHO-recommended treatments — rather than offering them sequentially — resulted in dramatic improvements in outcomes for women. Severe bleeding — when a woman loses more than a litre of blood after birth — was reduced by 60%, and they were less likely to lose their life.
There was also a substantial reduction in the rate of blood transfusions for bleeding, which is of particular importance in low-income countries where blood is a scarce and expensive resource.
Professor Arri Coomarasamy, who led the E-MOTIVE trial and is the Co-Director of the WHO Collaborating Centre on Global Women’s Health at the University of Birmingham said:
“This new approach to treating postpartum haemorrhage could radically improve women’s chances of surviving childbirth globally, helping them get the treatment they need when they need it.
“Time is of the essence when responding to postpartum bleeding, so interventions that eliminate delays in diagnosis or treatment should be gamechangers for maternal health. With this latest study showing that E-MOTIVE is extremely cost effective, and following WHO recommending the treatment bundle we hope that the intervention can quickly become the standard of care that will save many lives around the world.

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Hidden challenges of tooth loss and dentures revealed in new study

Improvements in dental care, more people living longer and the social value placed on having a healthy smile has led to people keeping their own teeth longer, but it has also led to an increasing number of people needing some kind of restoration work including crowns, bridges and implants.
Many of these treatments remain unobtainable for most people due to the availability of NHS dentists and the high cost of private dental work. Removable dentures are often the only viable option for anyone experiencing tooth loss with an estimated 10 to 15 percent of the population wearing them.
A new study by researchers at the University of Sheffield’s Healthy Life Span Institute and the School of Clinical Dentistry has highlighted the emotional struggles and hidden challenges patients experience when having dentures fitted. This is the first study to map out the patient journey and how this experience can affect the overall success of the treatment.
The study found that patients think about their denture journey in four stages: Tooth Loss: This is the initial stage where patients experience the physical loss of teeth. The Emotional Tunnel: This stage focuses on the emotional rollercoaster of tooth loss. Patients experience self-consciousness, depression, and struggle with dentures. They may feel shame, anger, or fear, but also hope. Prosthetic Hope: This stage represents the hope and optimism patients feel when getting dentures. They might anticipate regaining their smile and ability to eat normally. Prosthetic Compromise leading to managing disclosure: This final stage acknowledges that dentures take some getting used to. Patients might need to adjust their expectations and learn how to manage talking and eating with dentures. They might also develop strategies to feel comfortable disclosing their denture use to others.These feelings and how dentists understand and manage them can influence the patient outcomes. A dentist’s empathy during this adjustment period is crucial for successful denture use and better patient outcomes.
The study also identified that wearing removable dentures can be a hidden disability for many. People with dentures feel they have to hide them due to feeling embarrassed or worrying they will fall out. Some patients also avoided social situations
Lead researcher Barry Gibson, Professor in Medical Sociology at the University of Sheffield said “Tooth loss can be hugely traumatic and this study has uncovered just how challenging it is for people needing partial dentures. Feelings such as embarrassment or shame can significantly affect the process of having dentures made and fitted. On top of this if they don’t fit properly this can make everyday activities such as speaking, eating and drinking very difficult which affects a person’s quality of life. The impact can be so dramatic that it can impact their confidence to leave the house. This can have a devastating and lasting impact.

“Understanding the emotional difficulties identified in the study will help dentists to improve the care given to denture patients and lead to a more successful and better experience for everyone”
The research team partnered with local Sheffield artist Gina Allen to create an art piece reflecting the diverse emotional journeys of denture wearers.
The picture is a collage that illustrates the type of journeys patients go through from tooth loss to life with a denture. It uses colour to depict the emotional nature of the journey and demonstrates that all patients have a unique journey and outcome from the experience. One patient, a young woman, has a successful outcome; a middle-aged man is OK but a bit ‘Meh!’ An older woman continues to struggle to cope with some aspects of adapting to her denture.
Artist Gina Allen said “I’m a visual artist with a science background and a particular interest in how art can help to explore and interpret data, often around social and environmental themes. It seemed to me that there was such a depth and variety of individual experiences captured by the research team on this project, so it was a really interesting challenge to be involved in, trying to use the visual parameters of an artwork to convey some of that in an engaging and meaningful way.”
This collaboration has influenced the development of a new patient questionnaire designed to: Identify Individual Needs: Tailor care based on specific patient experiences. Improve Communication: Enable dentists and patients to have open conversations about dentures. Trigger Follow-Up: Identify patients who may need additional support.In addition to identifying the emotional challenges faced by patients, the study also highlights the need for a clinical care pathway to improve patient support, focus on improving denture fit, educate patients about denture care, and combat the shame and stigma associated with wearing dentures.
Mr Bilal El-Dhuwaib, Clinical Teacher in Restorative Dentistry at the University of Sheffield, said: “This study is important because it goes beyond the typical numbers-driven approach to dentistry by looking at crucial aspects of patients’ emotions and lived experiences. By understanding the psychological and social impact of tooth loss and replacement, the research provides a valuable toolkit for myself and fellow dentists to better understand and address the emotional rollercoaster patients navigate during this process. By equipping dentists with the tools to understand these challenges, we can create a more compassionate and effective approach to tooth replacement.”
The research team is seeking further funding to validate the questionnaire and develop a comprehensive clinical pathway for denture care. This pathway aims to improve patient outcomes and address the hidden struggles faced by denture wearers.
This study, published in The Journal of Dentistry was funded by consumer health company Haleon.

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How medical models can transform agriculture

Researchers in the Department of Civil and Environmental Engineering at Carnegie Mellon University are using findings from nanomedicine and digital twin technologies to understand the new field of Plant Nanobiotechnology, address unsustainable agricultural practices, and meet increasing global food demands.
Currently, agriculture accounts for 14-28% of global greenhouse gas emissions and 70% of all freshwater withdraws. This, in addition to a range of other factors from extreme weather events, rampant crop pests, and rapidly degrading soil underlines the need for new agricultural practices and technologies.
In a new study published in Nature Nanotechnology, researchers highlight that Plant Nanobiotechnology approaches can be used to deliver nanoforms of active agents, such as micronutrients or plant protection products, to specific biological targets. As a result, plants become more resilient against disease and harmful environmental factors like extreme heat or salt contents in soil, thus increasing crop yield and overall efficiency. However, because the field of Plant Nanobiotechnology is still in its nascent stages, many of the challenges to implementing new tools like nanocarriers are still unknown to researchers.
To overcome this obstacle, civil and environmental engineering professor Greg Lowry, in collaboration with co-corresponding author Juan Pablo Giraldo at University of California Riverside, colleagues, and students, is looking beyond plants and agriculture to find solutions inspired by nanomedicine.
“We found that the challenges of using nanocarriers to deliver nutrients in plants parallel those in nanomedicine, which has the advantage of being an established and well-studied field,” said Lowry. “While there are some key differences between plants and animals, many important parts of our research have been informed by nanomedicine, including identifying nanocarrier designs that can ensure active agents are effectively packaged, delivered, and released where they are needed.”
Similar to nanomedicine, researchers found that nanocarriers are most successful when they interact well with the organism they’re targeting, navigate key biological barriers, and take advantage of natural processes while minimizing unintended consequences. The study also explored the potentially transformative approach of creating “digital twins” of plants for assessing the efficacy of different nanocarrier designs.
Digital twins are breakthrough modeling technologies that have been widely used throughout infrastructure management, predictive maintenance, and manufacturing. Their unique ability to analyze a structure and its surrounding conditions, process the information, and use it to inform, predict, and modify what happens in the physical world has revolutionized the way researchers process data.
Just as medical researchers use “digital patients,” or digital twin models to simulate how medicines interact with and move within the body, Lowry and his team could use “digital plants” to facilitate the design of nanocarriers that target nutrient delivery to selected plant organs. In doing so, nanocarriers would be better equipped to deliver essential active agents where and when they’re needed most, increasing their effectiveness, resilience to adversity, and overall agricultural output.
“Nano-enabled precision delivery of active agents in plants will transform agriculture, but there are critical technical challenges that we must first overcome to realize the full range of its benefits,” said Lowry. “I’m optimistic about the future of Plant Nanobiotechnology approaches and the beneficial impacts it will have on our ability to sustainably produce food.”

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Macrophages behave like mural cells to promote healing of ischemic muscle injury

Innate immune cells including macrophages and neutrophils have unique properties that allows them to quickly accumulate in large numbers at the site of infection or injury. A new study from researchers at Uppsala University establishes that macrophage in the adult ischemic muscle induce a phenotype switch into mural cells to support restoration of functional blood flow and thereby promote healing. This finding pinpoints macrophages as a potential target for therapeutically enhancing vascular integrity and healing of ischemic injuries.
Manifestations of cardiovascular diseases are caused by impaired tissue perfusion, and subsequent injury and loss of tissue function. Rapid re-establishment of functional blood flow is critical following an ischemic event to limit the extent and severity of tissue damage, as well as allowing for healing and regaining function. A hallmark of ischemic injury is rapid accumulation of immune cells including macrophages at the affected site, which is crucial for tissue regeneration and remodeling.
In injured muscle, including human infarcted myocardium, macrophages were recently described to localize to perivascular positions where they become more elongated and embrace the newly formed vasculature. This cellular morphology resembles that of mural cells, which are crucial for maintaining blood flow by reducing vascular leakage and promoting vessel maturation, but whether macrophages in injured muscle take on mural cell functions to improve healing have not been explored.
The current study, published in Nature Cardiovascular Research, demonstrates that perivascular macrophages in the ischemic muscle upregulated several proteins that are associated with mural cells while downregulating those associated with immune cell functions. Single-cell RNA-sequencing of fate-mapped macrophages from ischemic mouse muscles identified a subpopulation of macrophages that shifted their transcriptome from expression of macrophage markers to mural cell markers such as PDGFRβ. This macrophage switch was proven functionally relevant, as induction of macrophage-specific PDGFRβ-deficiency prevented their perivascular macrophage phenotype, impaired vessel maturation and increased vessel leakiness, which ultimately reduced limb function. Thus, macrophages in injured tissues not only develop a mural cell-like morphology and transcriptome but also adopt mural cell functions that are important for healing ischemic injuries.
In conclusion, macrophages in adult ischemic tissue were demonstrated to undergo a cellular program to morphologically, transcriptomically and functionally resemble mural cells while weakening their macrophage identity. The macrophage-to-mural cell-like phenotypic switch is crucial for restoring tissue function and demonstrate that innate immune cells in adult tissue can serve as a cellular resource and take over functions of other cell types to promote tissue repair. This novel finding warrants further exploration as a potential target for immunotherapies to enhance healing.

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First-of-its-kind test can predict dementia up to nine years before diagnosis

Researchers at Queen Mary University of London have developed a new method for predicting dementia with over 80% accuracy and up to nine years before a diagnosis. The new method provides a more accurate way to predict dementia than memory tests or measurements of brain shrinkage, two commonly used methods for diagnosing dementia.
The team, led by Professor Charles Marshall, developed the predictive test by analysing functional MRI (fMRI) scans to detect changes in the brain’s ‘default mode network’ (DMN). The DMN connects regions of the brain to perform specific cognitive functions and is the first neural network to be affected by Alzheimer’s disease.
The researchers used fMRI scans from over 1,100 volunteers from UK Biobank, a large-scale biomedical database and research resource containing genetic and health information from half a million UK participants, to estimate the effective connectivity between ten regions of the brain that constitute the default mode network.
The researchers assigned each patient with a probability of dementia value based on the extent to which their effective connectivity pattern conforms to a pattern that indicates dementia or a control-like pattern.
They compared these predictions to the medical data of each patient, on record with the UK Biobank. The findings showed that the model had accurately predicted onset of dementia up to nine years before an official diagnosis was made, and with greater than 80% accuracy. In the cases where the volunteers had gone on to develop dementia, it was also found that the model could predict within a two-year margin of error exactly how long it would take that diagnosis to be made.
The researchers also examined whether changes to the DMN might be caused by known risk factors for dementia. Their analysis showed that genetic risk for Alzheimer’s disease was strongly associated with connectivity changes in the DMN, supporting the idea that these changes are specific to Alzheimer’s disease. They also found that social isolation was likely to increase risk of dementia through its effect on connectivity in the DMN.
Charles Marshall, Professor and Honorary Consultant Neurologist, led the research team within the Centre for Preventive Neurology at Queen Mary’s Wolfson Institute of Population Health. He said: “Predicting who is going to get dementia in the future will be vital for developing treatments that can prevent the irreversible loss of brain cells that causes the symptoms of dementia. Although we are getting better at detecting the proteins in the brain that can cause Alzheimer’s disease, many people live for decades with these proteins in their brain without developing symptoms of dementia. We hope that the measure of brain function that we have developed will allow us to be much more precise about whether someone is actually going to develop dementia, and how soon, so that we can identify whether they might benefit from future treatments.”
Samuel Ereira, lead author and Academic Foundation Programme Doctor at the Centre for Preventive Neurology, Wolfson Institute of Population Health, said: “Using these analysis techniques with large datasets we can identify those at high dementia risk, and also learn which environmental risk factors pushed these people into a high-risk zone. Enormous potential exists to apply these methods to different brain networks and populations, to help us better understand the interplays between environment, neurobiology and illness, both in dementia and possibly other neurodegenerative diseases. fMRI is a non-invasive medical imaging tool, and it takes about 6 minutes to collect the necessary data on an MRI scanner, so it could be integrated into existing diagnostic pathways, particularly where MRI is already used.”

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